samecniero SromaTa krebuli Collection of Scientific works

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1 II saertasoriso samecniero konferencia II International Scientific Conference,,farmacevtuli mecnierebebi XXI saukunesi,,pharmaceutical Sciences in XXI Century samecniero SromaTa krebuli Collection of Scientific works Tbilisis saxelmwifo samedicino universiteti, Tbilisi, saqartvelo 2-4 maisi, 2014 Tbilisi State Medical University, Tbilisi, Georgia May 2-4,

2 misasalmebeli sityva mogesalmebit II saertasoriso samecniero konferenciis farmacevtuli mecnierebebi XXI saukunesi monawileebs. gisurvebt nayofier da warmatebul musaobas. CvenTvis didi pativia vumaspinzlot samecniero forums. gansakutrebit arnisvnis Rirsia is faqti, rom konferencia ezrvneba qartuli farmaciis patriarqis, damsaxurebuli pedagogisa da mecnieris, sazogado morvawis, profesor bizina WumburiZis saxelovan iubiles - dabadebidan 90 wlistavs. profesor bizina WumburiZis dremde ganvlili gza nateli magalitia TiToeuli CvenganisaTvis da gansakutrebit axalgazrdobisatvis Tu rogor unda icxovro da imorvaweo dargis, qveynisa da eris saketildreod. globalizaciis procesma TiToeuli Cvengani axali gamowvevebis winase daayena da mnisvnelovani gaxada ara marto ertiani valutis, ekonomikisa da politikis, aramed ertiani mecnierebisa da ganatlebis sistemis Seqmna, romelic dafuznebuli iqneba urtierttanamsromlobaze, codnisa da gamocdilebis gacvla - gaziarebaze. Cveni Tavyriloba dasturia imisa, rom forumis monawileebs bevri gvaqvs saerto mecnieruli TvalTaxedviT, swored amitomac gansakutrebit mnisvnelovania Cveni kvlevis Sedegebis ertoblivi ganxilva da samomavlod ertoblivi kvleviti proeqtebis ganxorcieleba. samecniero konferenciasi monawileobas Rebuloben ara marto qartuli saganmanatleblo Tu samecniero centrebis warmomadgenlebi, aramed ucxoeli stumrebic. sainteresoa konferenciis Tematikac, romelic iset aqtualur Temebs moicavs, rogorebicaa bunebrivi resursebis kvleva medicinasi gamoyenebis miznit, samkurnalo sasualebebis Seqmna da standartizacia, qimiurtoqsikologiuri analizi, farmacevtuli saqmianobis regulireba da mravali sxva. damerwmunebit, rom interesta sfero martlac mravalferovania, magram ufro mnisvnelovania is, rom konferencia samecnierostan ertad praqtikul mnisvnelobasac atarebs, rac xels Seuwyobs novaciebis danergvasa da kvlevebis axal etapze ganxorcielebas. drevandeli forumi mnisvnelovania rogorc gamocdilebis gaziarebis, aseve axali urtiertobebis CamoyalibebisaTvis. saorganizacio da samecniero komitetis saxelit madlierebis grznobit mivmartavt samecniero konferenciis mxardamwerebs: FAfarmacevtul sawarmo GMP -is, farmacevtul kompania averss, farmacevtuli kompaniebis warmomadgenelta asociacias saqartvelosi; amastan, gvinda gza davulocot am mnisvnelovan samecniero forums da nayofieri samecniero da praqtikuli Sedegebi vusurvot mas. II saertasoriso samecniero konferenciis farmacevtuli mecnierebebi XXI saukunesi, saorganizacio komiteti 2

3 mowveuli saertasoriso momxseneblebi International Invited Speakers Professor Vassilios Roussis, Director of the Laboratory of Pharmacognosy, School of Pharmacy, University of Athens, Greece profesori vasilios rousis, atenis universitetis farmaciis skolis farmakognoziis laboratoriis direqtori, saberzneti Professor Francisco Macias, Department of Organic Chemistry, Allelopathy Group, Director of Institute of Biomolecules (INBIO-UCA), School of Sciences, University of Cadiz, Spain profesori francisko maciasi, organuli qimiis departamenti, alelopatiis jgufi, biomolekulebis institutis direqtori, mecnierebata skola, cadizis universiteti, espaneti Professor Hermann Stuppner, Head of the Institute of Pharmacy/pharmacognosy at the University Innsbruck, Austria profesori herman stupneri, insbrukis universitetis farmaciis/farmakognoziis institutis xelmzrvaneli, avstria Professor Wieslaw Oleszek, Director of the Institute of Soil Science and Plant Cultivation State Research Institute, Pulawy, Poland profesori vislav olesek, miwatmecnierebisa da mcenareta kultivaciis saxelmwifo kvleviti institutis direqtori, pulavi, poloneti 3

4 Professor Johann Gasteiger, Computer-Chemie-Centrum and Institute for Organic Chemistry, University of Erlangen Nurnberg, Germany profesori iohan gastaiger, kompiuteruli-qimiis centri da organuli qimiis instituti, erlangennumbergis universiteti, germania Associated Professor Adam Matkowski, Head of the Department of Botany and Pharmaceutical Biology, Medical University of Wroclaw, Poland profesori adam matkovski, botanikisa da farmacevtuli biologiis departamentis xelmzrvaneli, vroclavis samedicino universiteti, poloneti Professor Pascal Rathelot, Laboratory of Therapeutic and mineral chemistry, Aix-Marseille Université, France profesori paskal Ratlo, Terapiuli da mineraluri qimiis laboratoria, eqs-marselis universiteti, safrangeti. 4

5 II saertasoriso samecniero konferencia II International Scientific Conference,,farmacevtuli mecnierebebi XXI saukunesi,,pharmaceutical Sciences in XXI Century programa FINAL PROGRAMME Tbilisis saxelmwifo samedicino universiteti, Tbilisi, saqartvelo 2-4 maisi, 2014 Tbilisi State Medical University, Tbilisi, Georgia May 2-4,

6 II saertasoriso samecniero konferencia,,farmacevtuli mecnierebebi XXI saukunesi Tbilisis saxelmwifo samedicino universiteti, Tbilisi, saqartvelo 2-4 maisi, 2014 programa konferenciis organizatorebi Tbilisis saxelmwifo samedicino universiteti saqartvelos farmacevtta asociacia q. Tbilisis farmacevtta kavsiri saorganizacio komiteti zurab vadawkoria zurab orjonikize rima beriasvili kaxa WeliZe irina kvawaze bizina WumburiZe aliosa bakurize roman maxaraze dali berasvili samecniero komiteti lia adeisvili nato alavize meri alania neli antelava badri arziani qetevan baramize ramaz gaxokize marina giorgobiani nana gorgaslize genri dekanosize vaja eriasvili valentina vacnaze nino vefxvaze bizina zurasvili paata TuSuraSvili pavle iavici luiza kunwulia jumber kuwuxize nაnა lasauri vladimer maxaraze nestan merkvilaze gulnara miqaia ipolite moniava Tamaz murtazasvili revaz sxilaze durmisxan turabelize jemal futkaraze zurab qemoklize naili SengeliZe Tamar CikvilaZe guram cagareisvili davit WinWaraZe Tamaz WumburiZe madona jorjikia malxaz joxaze saertasoriso samecniero komiteti francisko maciasi (espaneti) herman stupneri (avstria) vasilios rousisi (saberzneti) vislav oleseki (poloneti) joan gastaigeri (germania) adam matkovski (poloneti) paskal Ratlo (safrangeti) sonia piacente (italia) saredaqcio komiteti ana bojaze natia gagua sofio goqaze nana durasvili nino imnaze natia kvijinaze lali lomtaze lasa msxilaze Tamar muzasvili nino nemsiwverize nino nijaraze Tamar otarasvili nino qurdiani ia wurwumia nino cagareisvili konferenciis finansuri mxardamwerebi farmacevtuli sawarmo GMP generaluri sponsori farmacevtuli kompania aversi platinis sponsori farmacevtuli kompaniebis warmomadgenelta asociacia saqartvelosi oqros sponsori 6

7 II International Scientific Conference,,Pharmaceutical Sciences in XXI Century Tbilisi State Medical University, Tbilisi, Georgia May 2-4, 2014 PROGRAMME ORGANIZERS Tbilisi State Medical University Georgian Assotiation of Pharmacists Tbilisi Pharmacy Corporation ORGANIZING COMMITTEE Zurab Vadachkoria Zurab Orjonikidze Rima Beriashvili Kakha Chelidze Irina Kvachadze Bidzina Chumburidze Aliosha Bakuridze Roman Makharadze Dali Berashvili SCIENTIFIC COMMITTEE Lia Adeishvili Nato Alavidze Meri Alania Neli Antelava Badri Arziani Ketevan Baramidze Tamar Chikviladze Davit Chincharadze Tamaz Chumburidze Genri Dekanosidze Vazha Eriashvili Ramaz Gakhokidze Marina Giorgobiani Nana Gorgaslidze Pavle Iavichi Malkhaz Jokhadze Madona Jorjikia Jumber Kuchukhidze Luisa Kunchulia Nana Lashauri Vladimer Makharadze Nestan Merkviladze Gulnara Miqaia Ipolite Moniava Tamaz Murtazashvili Jemal Phutkaradze Zurab Qemoklidze Naili Shengelidze Revaz Skhiladze Guram Tsagareishvili Durmishkhan Turabelidze Paata Tushurashvili Valentina Vachnadze Nino Vephkhvadze Bidzina Zurashvili INTERNATIONAL SCIENTIFIC COMMITTEE Francisco Macias (Spain) Hermann Stuppner (Austria) Vassilios Roussis (Greece) Wieslaw Oleszek (Poland) Johann Gasteiger (Germany) Adam Matkowski (Poland) Pascal Rathelot (France) Sonia Piacente (Italy) ADDITORIAL COMMITTEE Ana Bozhadze Nino Cagareishvili Natia Gagua Sopio Gokadze Nana Dughashvili Nino Kurdiani Nino Imnadze Natia Kvizhinadze Lali Lomtadze Lasha Mskhiladze Tamar Muzashvili Nino Nemsitsveridze Nino Nizharadze Tamar Otarashvili Ia Tsurtsumia SPONSORS GM Parmaceuticals General sponsor Parmaceutical company AVERSI Platinum sponsor Association of Pharmaceutical Companies Representatives in Georgia Golden sponsor 7

8 II saertasoriso samecniero konferencia,,farmacevtuli mecnierebebi XXI saukunesi Tbilisis saxelmwifo samedicino universiteti, Tbilisi, saqartvelo 2-4 maisi, 2014 informacia konferenciis Catarebis adgili Tbilisis saxelmwifo samedicino universiteti, 2-4 maisi, 2014 registracia Tbilisis saxelmwifo samedicino universitetis administraciuli korpusi (vaja-fsavelas # 33) 2 maisi, 2014, konferenciis ena konferenciis oficialuri ena qartuli, inglisuri iubilis gaxsnis ceremonia Tbilisis saxelmwifo samedicino universitetis administraciuli korpusi (vaja-fsavelas # 33) 2 maisi, 2014, konferenciis gaxsnis ceremonia Tbilisis saxelmwifo samedicino universitetis administraciuli korpusi (vaja-fsavelas # 33) 3 maisi, 2014, socialuri RonisZiebebi sazeimo vaxsami 2 maisi, 2014, koncerti 4 maisi, 2014, eqskursia 4 maisi, 2014,

9 II International Scientific Conference,,Pharmaceutical Sciences in XXI Century Tbilisi State Medical University, Tbilisi, Georgia May 2-4, 2014 Conference Venue Tbilisi State Medical University, 2-4 May, 2014 Registration Tbilisi State Medical University administration building (# 33 Vazha-Pshavela Avenue) 2 May, 2014, GENERAL INFORMATION Language The official language of the Conference is Georgian and English Anniversary Opening Ceremony Tbilisi State Medical University administration building (# 33 Vazha-Pshavela Avenue) 2 May, 2014, Conference Opening Ceremony Tbilisi State Medical University administration building (# 33 Vazha-Pshavela Avenue) 3 May, 2014, Social Events Welcome Dinner 2 May, 2014, Concert - 4 May, 2014, Excursion 4 May, 2014,

10 II saertasoriso samecniero konferencia,,farmacevtuli mecnierebebi XXI saukunesi Tbilisis saxelmwifo samedicino universiteti, Tbilisi, saqartvelo 2-4 maisi, 2014 konferenciis pirveli dre 2 maisi registracia iubilis gaxsnis ceremonia _ profesor bizina WumburiZis cxovreba da morvaweoba aliosa bakurize, saqartvelos farmacevtta asociaciis vice-prezidenti, profesori saiubileo misalmebebi sazeimo vaxsami 10

11 II International Scientific Conference,,Pharmaceutical Sciences in XXI Century Tbilisi State Medical University, Tbilisi, Georgia May 2-4, 2014 First Day of the Conference May, Registration Anniversary Opening Ceremony _ _ Scientific and Creative Life of Professor Bidzina Chumburidze Aliosha Bakuridze, Vice President of Georgian Assotiation of Pharmacists, Professor Anniversary Meeting, Greetings Welcome Dinner 11

12 II saertasoriso samecniero konferencia,,farmacevtuli mecnierebebi XXI saukunesi Tbilisis saxelmwifo samedicino universiteti, Tbilisi, saqartvelo 2-4 maisi, 2014 konferenciis meore dre 3 maisi Tavmjdomareebi: I plenaruli sesia dali berasvili (saqartvelo), herman stupneri (avstria) konferenciis gaxsnis ceremonia bizina WumburiZe (saqartvelo): farmaciis ganvitarebis istoriuli etapebi saqartvelosi francisko maciasi (espaneti): alelopatia axali samkurnalo sasualebebis ZiebaSi vasilios rousis (saberzneti): biologiurad aqtiuri bunebrivi produqtebi zrvis organizmebidan kofe-breiki adam matkovski (poloneti): tradiciuli aziuri samkurnalo mcenareebi rogorc antioqsidanturi da antebis sawinaarmdego nivtierebebis wyaro maia okujava (saqartvelo): awaris regionsi gavrcelebuli lamiani sulfiduri talaxebis antebis sawinaarmdego aqtivoba da gamoyenebis usafrtxoeba salavat xalikovi (ruseti): wamlis miznobrivi miwodebis sistemebi benzimidazolebis antihelminturi substanciebistvis natia gagua (saqartvelo): Vinca herbacea-s Waldst. et Kit. leikopoezis mastimulirebeli indolis alkaloidebis analizi elene wiwilasvili (saqartvelo): meloqsikamis Semcveli medikamentebis xarisxis kontroli lanci 12

13 II International Scientific Conference,,Pharmaceutical Sciences in XXI Century Tbilisi State Medical University, Tbilisi, Georgia May 2-4, 2014 Second Day of the Conference May, 3 Chairs: Dali Berashvili (Georgia), Hermann Stuppner (Austria) Plenary Session I The Conference Opening Ceremony KL: Bidzina Chumburidze (Georgia): Historical stages in the development of Pharmacy in Georgia PL1: Francisco Macias (Spain): Allelopathy in the search new drugs PL2: Vassilios Roussis (Greece): Bioactive natural products from Marine organisms Coffee Break IL1: Adam Matkowski (Poland): Traditional Asian medicinal plants as source of antioxidant and anti-inflammatory compounds IL2: Maia Okujava (Georgia): Anti-inflammatory action and safety of sulphide sild peloids, distributed in Adjara Region SL1: Salavat Khalikov (Russia): Targeted drug delivery systems for anthelmitic substances of benzimidazoles SL2: Natia Gagua (Georgia): Analysis of indolic alkaloids from Vinca herbacea W. Et. K. stimulators of leucopoiesis SL3: Elene Tsitsilashvili (Georgia): The quality control of Meloxicam containing medicines Lunch Break 13

14 II saertasoriso samecniero konferencia,,farmacevtuli mecnierebebi XXI saukunesi Tbilisis saxelmwifo samedicino universiteti, Tbilisi, saqartvelo 2-4 maisi, 2014 konferenciis meore dre 3 maisi Tavmjdomareebi: II plenaruli sesia karen mulkijaniani (saqartvelo), vislav oleseki (poloneti) herman stupneri (avstria): mcenareta samefo potenciuri antebis sawinaarmdego wamyvani nivtierebebis mdidari wyaro paskal Ratlo (safrangeti): axali antiplazmodiuri heterocikluri hit-senaertebis moqmedebis meqanizmis Seswavla aliosa bakurize (saqartvelo): wamlis mizanmimartuli miwodebis sistemebisa da formebis Seswavla da SemuSaveba levon a. melikian (somxeti): efeqturi da SerCeviTi RP-HPLC metodis SemuSaveba da validacia bela kikalisvili (saqartvelo): saqartvelosi mozardi Amaranthus cruentus L, A.retroflexsus L, A.blitoides s.wats Teslebis lipidebi nino imnaze (saqartvelo): olanzapinis gansazrvra adamianis sisxlsi sitxur qromatografiuli mas speqtrometruli (LC/MS/MS) metodit kofe-breiki 14

15 II International Scientific Conference,,Pharmaceutical Sciences in XXI Century Tbilisi State Medical University, Tbilisi, Georgia May 2-4, 2014 Second Day of the Conference May, 3 Chairs: Karen Mulkijanyan (Georgia), Wieslaw Oleszek (Poland) Plenary Session II PL3: Hermann Stuppner (Austria): The plant kingdom a rich source for potential anti-inflammatory lead compounds IL3: Pascal Rathelot (France): Studing the mechanism of action of new antiplasmodial heterocyclic hitcompounds via a solid supported chemistry approach Il4: Aliosha Bakuridze (Georgia): Study and development of targeted drug delivery systems and dosage forms SL4: Levon A. Melikyan (Armenia): Development and validation of efficient and selective RP-HPLC method for simultaneous determination of guaifenesin impurities in the presence of guaifenesin, ambroxol hydrochloride and salbutamol sulfate in multi drug components pharmaceutical formulations SL5: Bela Kikalishvili (Georgia): Lipids of seeds Amaranthus cruentus L, A. Retroflexus L, A. blitoides S. Wats growing in Georgia SL6: Nino Imnadze (Georgia): Determination of Olanzapine in whole blood using Liquid Chromatography tandem Mass Spectrometry (LC/MS/MS) Coffee Break 15

16 II saertasoriso samecniero konferencia,,farmacevtuli mecnierebebi XXI saukunesi Tbilisis saxelmwifo samedicino universiteti, Tbilisi, saqartvelo 2-4 maisi, 2014 konferenciis meore dre 3 maisi Tavmjdomareebi: III plenaruli sesia aliosa bakurize (saqartvelo), vasilios rousis (saberzneti) karen mulkijaniani (saqartvelo): ojaxi Boraginaceae-s zogierti saxeobis biologiurad aqtiuri polieterebi da mati sintezuri warmoebulebi: perspeqtiuli Terapiuli agentebi naira CiCoiani (somxeti): somxuri gargaris fisebis qimiuri struqturebis da antimikrobuli aqtivobis kvleva iulia prokopenko (ukraina): axali mcenareuli antikonvulsantebis Zieba aleqsandre cercvaze (saqartvelo): amlodipinis besilatis qromatografiuli analizi analizuri metodis ganvitareba vaxsami 16

17 II International Scientific Conference,,Pharmaceutical Sciences in XXI Century Tbilisi State Medical University, Tbilisi, Georgia May 2-4, 2014 Second Day of the Conference May, 3 Chairs: Aliosha Bakuridze (Georgia), Vassilios Roussis (Greece) Plenary Session III IL5: Karen Mulkijanyan (Georgia): Biologically active polyethers from different species of Boraginaceae family and their synthetic derivatives: prospective therapeutic agents SL7: Naira ChiChoyan (Armenia): The research of chemical structures and antimicrobial activity of Armenian Apricot gums (Gummi Armeniacae) SL8: Yulya Prokopenko (Ukraine): The search of new herbal anticonvulsants SL9: Alexander Tsertsvadze (Georgia): Chromatographic analysis of Amlodipine besylate an analytical method development Dinner 17

18 II saertasoriso samecniero konferencia,,farmacevtuli mecnierebebi XXI saukunesi Tbilisis saxelmwifo samedicino universiteti, Tbilisi, saqartvelo 2-4 maisi, 2014 konferenciis mesame dre 4 maisi IV plenaruli sesia Tavmjdomareebi: bizina WumburiZe (saqartvelo), francisko maciasi (espaneti) vislav oleseki (poloneti): fitoqimia axali aqtiuri bunebrivi nivtierebebis ZiebaSi meri alania (saqartvelo): saqartvelos floris zogierti saxeobis meoreuli metabolitebi: fundamenturi da gamoyenebiti aspeqtebi SoTa jibuti (saqartvelo): farmako-zedamxedvelobis da wamalta gverditi movlenebis monitoringis principebi margarita beglariani (somxeti): momxmareblis qcevaze momqmedi farmacevtuli warmoebis zogierti faqtoris Seswavla kofe-breiki gulnara miqaia (saqartvelo): awaris regionsi gavrcelebuli mineraluri resursebis kvleva medicinasi gamoyenebis miznit gvanca gvritisvili (saqartvelo): fluoqsetinis raodenobrivi gansazrvris metodis damusaveba adamianis sisxlis plazmis modelze Sorena cxadaze (saqartvelo): ofloqsacinis Semcveli preparatis kafras mg-iani tabletebis bioveiveruli Seswavla, bioeqvivalentobis kvlevisgan gantavisuflebis miznit vork-sopi momxseneblebi: giorgi antaze, lali datesize, marina giorgobiani lanci stenduri moxsenebebi moderatorebi: Tamar CikvilaZe, adam matkovski, paskal Ratlo konferenciis daxurva koncerti eqskursia 18

19 II International Scientific Conference,,Pharmaceutical Sciences in XXI Century Tbilisi State Medical University, Tbilisi, Georgia May 2-4, 2014 Third Day of the Conference May, 4 Plenary Session IV Chairs: Bidzina Chumburidze (Georgia), Francisco Macias (Spain) PL4: Wieslaw Oleszek (Poland): Phytochemistry searching for a new active natural compounds IL6: Meri Alania (Georgia): Secondary metabolites from some plants of Georgian flora: fundamental and using aspects SL10: Shota Jibuti (Georgia): The principles of pharmacovigilance and the monitoring of adverse drug reaction SL11: Margarita Beglaryan(Armenia): Study of the pharmaceutical production some factors influencing on the consumers behavior Coffee Break SL12: Gulnara Mikaia (Georgia): Investigation of Peloids, spread in Adjarian region for using in medicine and cosmetology practice SL13: Gvantsa Gvritishvili (Georgia): Method for determining the quantity of fluoxetine on the model of human blood SL14: Shorena Tskhadadze (Georgia): Ofloxacin containing tablets,,kafra 400 mg, biowaiver stadying procedure on based BCS, according to WHO Work-shops Speakers: Giorgi Antadze, Lali Dateshidze, Marina Giorgobiani Lunch Break Poster Session Moderators: Tamar Chikviladze, Adam Matkowski, Pascal Rathelot Closing Ceremony Concert Excurssion 19

20 profesor bizina WumburiZis cxovreba da morvaweoba a. bakurize Tbilisis saxelmwifo samedicino universitetis farmacevtuli da toqsikologiuri qimiis katedris profesori, mediko-biologiuri da socialuri medicinis akademiis akademikosi bizina WumburiZe 90 wlis iubiles 68 wliani samecniero-pedagogiuri, 10 wliani administraciuli da 60 wliani sazogadoebrivi morvaweobit xvdeba. saxelmwifo premiis laureati, Rirsebis ordenis kavaleri, damsaxurebuli mecnieri, gamomgonebeli, medikosi, pedagogi da sazogado morvawe 1924 wlis 1 maiss qutaisis raionis sofel qveda simonetsi daibada. farmaciis specialobis Seswavla bizis, cnobili profesoris, pavle WumburiZis, rcevit gadawyvita da samamulo omis mzime wlebsi, Tbilisis saxelmwifo samedicino institutis farmacevtul fakultetis sruli kursi warcinebit daasrula. omis damtavrebis Semdeg akademikos iovel qutatelazes, stalinis saxelobis stipendianti studentisatvis katedris TanamSromlad darcena SeuTavazebia da mas Semdeg modis da mouyveba mecnierebis mwvervalebisaken. rigiti laborantidan - katedris xelmzrvanelobamde - esaa batoni bizinas mier ganvlili gza, romelic gansakutrebul madlierebas Tavisi maswavleblis, aristrax msvidobazis, mimart gamoxatavs, romlis xelmzrvanelobitac 30 weli imusava farmacevtuli qimiis katedraze. gavixsenot ramdenime epizodi iubilaris biografiidan da natlad davinaxavt Tu ramdenad Rrma da Sinaarsiani cxovreba ganvlo man: ww. Tbilisis saxelmwifo samedicino institutis farmacevtuli qimiis katedris asistentia; ww. Tbilisis saxelmwifo samedicino institutis farmacevtuli qimiis katedris docentia; ww. Tbilisis saxelmwifo samedicino institutis farmacevtuli qimiis katedris profesoria; ww. Tbilisis saxelmwifo samedicino institutis farmacevtuli qimiis katedris gamgea; 1996 wlidan dremde Tbilisis saxelmwifo samedicino universitetis farmacevtuli da toqsikologiuri qimiis departamentis profesoria; ww. saqartvelos janmrtelobis dacvis saministros farmakopeis komitetis Tavmjdomare da 1992 wlidan dremde ilia WavWavaZis saxelobis sazogadoeba codnis samedicino kolejis profesoria. batoni bizina, miuxedavad siwarmagisa, Tbilisis saxelmwifo samedicino universi-tetis reqtoris mrcevelta sabwos wevria da bolomde ixarjeba msobliuri universitetisatvis wels bizina WumburiZes mieniwa farmacevtul mecnierebata kandidatis, xolo 1964 wels farmacevtul mecnierebata doqtoris xarisxebi. misi mecnieruli produqtiuloba kvlevebsa da publikaciebsi aisaxa. gamoqveynebuli aqvs 250 samecniero nasromi, 8 20

21 saxelmzrvanelo farmacevtuli qimiis Teoriul da praqtikul sferosi, 4 damxmare saxelmzrvanelo, 3 monografia farmaciis aqtualur sakitxebze, 21 gamogonebaze aqvs saavtoro mowmoba. aqtiur samecniero saqmianobastan ertad Cveni iubilari momavali Taobis WeSmariti armzrdelicaa. misi xelmzrvanelobit daculi iqna 22 sakandidato da sadoqtoro disertacia, xolo 60-ze meti sadisertacio nasromis recenzent-oponenti gaxldat. qartuli farmaciis sinamdvilesi profesorma bizina WumburiZem safuzveli Cauyara mecnieruli kvlevis iset mimartulebebs, rogoricaa: qromatografiuli analizis metodebis SemuSaveba; narkologiur-toqsikologiuri analizi; samkurnalo preparatebis farmakokinetikuri kvleva; samkurnalo preparatebis standartizacia da sxva. mis saxels ukavsirdeba jer kidev 1948 wels, saqartvelosi pirvelad farmacevtul analizsi qromatografiuli metodebis gamoyeneba, am sferos pirveli 1950 wlis publikaciebic swored mas ekutvnis. man, saqartvelodan pirvelma, 1954 wels, moskovis farmacevtta sakavsiro samecniero konferenciaze gaaketa samecniero moxseneba Temaze: oqsimetilantraqinonebis qromatografiuli analizi, romlis Semdegac arnisnuli mimartulebit kvlevam farto masstabebi miiro, amis dasturia 1962 wels lomonosovis universitetsi saertasoriso samecniero konferenciaze qromatografiuli analizis sakitxebze mis mier gaketebuli 2 moxseneba. profesori bizina WumburiZis mecnieruli ariareba gaxldat is, rom am konferenciaze igi samecniero seqcias xelmzrvanelobda wels saqartvelos ministrta sabwosa da mecnierebisa da teqnikis saxelmwifo komitetis mier Seqmnil komisias, romelsac unda ezruna ioncvliti qromatografiuli metodebis danergvaze mrewvelobasi, profesori bizina WumburiZe Tavmjdomareobda. swored misi xelmzrvanelobit farmacevtul sawarmoebsa da kvebis mrewvelobasi ioncvliti qromatografiuli danadgarebi dainerga wlebsi damusavda da sakavsiro masstabit dainerga adamianis biologiur sitxeebsi narkotikebis gansazrvris qromatografiuli metodebi wels profesor bizina WumburiZis avtorobit gamoica monografia saxelwodebit ionmcvleli polimerebis gamokvleva medicinasi gamoyenebis miznit wels TbilisSi misi xelmzrvanelobita da organizebit Catarda sakavsiro simpoziumi - qromatografiuli metodebi farmaciasi, romelzec profesor b. WumburiZisa da misi samecniero skolis warmomadgenelta mier 12 moxseneba gaketda. xolo 1986 wels q. moskovsi Catarebul qromatografistta sakavsiro samecniero konferenciaze batonma bizinam moxseneba TanaavtorebTan ertad waradgina wlebsi batoni bizina iyo sabwota kavsiris mecnierebata akademiis qromatografiis saproblemo sabwos wevri. arnisnul sferosi mirweuli warmatebebisatvis igi sabwota kavsiris mecnierebata akademiam sapatio sigelit - qromatografiis ganvitarebisatvis kacobriobis saketildreod - daajildova. iubilaris mier saqartvelosi Seqmnili samecniero skolebisa da mimartulebebisagan gansakutrebit arsanisnavia samkurnalo preparatebis farmakokinetikuri kvlevebi. mis mier 1979 wels Tbilisis saxelmwifo samedicino institutis farmacevtuli qimiis katedrastan Camoyalibda seminari farmakokinetikis sakitxebze, romlis musaobasi samedicino institutis profesor-maswavleblebtan ertad monawileobdnen Terapiis s/k institutis, mean-ginekologiis s/k institutis, da fsiqiatriis s/k institutis mecnier- TanamSromlebi. 21

22 farmakokinetikis sakitxebze 1982 wels TbilisSi Catarda I sakavsiro samecniero konferencia, romlis saorganizacio komitetis Tavjdomaris moadgile da farmacevtuli qimiis katedris TanamSromlebTan ertad mnisvnelovani samecniero moxsenebebis avtori profesori bizina WumburiZe gaxldat. konferenciis masalebi gamoica 2 tomad. b. WumburiZe da farmacevtuli qimiis katedris TanamSromlebi samecniero moxsenebebit 1985 wels q. kaunassi Catarebul farmakokinetikosta II sakavsiro konferenciazec warsdgnen. profesor b. WumburiZe araerti wamowyebis avtori gaxldat. misi xelmzrvanelobit Tssu farmacevtuli da toqsikologiuri qimiis katedrastan Camoyalibda da wlebis manzilze funqcionirebda samkurnalo preparatebis standartizaciis laboratoria, romelmac mnisvnelovani wvlili Seitana saqartvelosi warmoebuli samkurnalo sasualebebis standartizaciis donis amarlebasi. misi TaosnobiT Sesrulda da gamoica fundamenturi xasiatis Sromebi samkurnalo sasualebata standartizaciis sakitxebze. igi aqtiurad monawileobda moskovis standartizaciisa da wamlis xarisxis kontrolis saxelmwifo institutis CamoyalibebaSi. arsanisnavia, rom batoni bizina qartuli xalxuri medicinis aqtiuri mkvlevaricaa. misi TaosnobiT 180 wamali iqna gamokvleuli, romeltagan ramdenime ateulze momzadda normatiuli dokumentacia da seriulad iwarmoeba. marali samecniero da praqtikuli RirebulebebiT gamoirceva profesor b. WumburiZis fundamenturi xasiatis Sromebi vazisa da futkris produqtebis kvlevebtan dakavsirebit. mravalwliani samecniero morvaweobis praqtikuli Sedegia misi TaosnobiT Seqmnili iseti efeqturi samkurnalo sasualebebi, rogorebicaa sanogeni, traceptini, dindgelis malamo da nayeni, apivenungi da sxva. garda zemot CamoTvlilisa, 1950 wlidan dremde bizina WumburiZe aris farmaciis sxvadasxva mimartulebis ara erti adgilobrivi Tu saertasoriso mnisvnelobis samecniero forumis organizatori da monawile. igi 1978 wels q. TbilisSi Catarebuli saqartvelos farmacevtuli sazogadoebis yrilobis saorganizacio komitets xelmzrvanelobda. misive redaqtorobit gamoica yrilobis masalebi. profesori b. WumburiZe aqtiurad monawileobda rogorc saqartvelos sxvadasxva qalaqebsi, aseve sakavsiro masstabit Catarebul samecniero yrilobebsa da konferenciebsi (sabwota kavsiris farmacevtta I yriloba, peterburgi 1958 weli, II yriloba piatigorsksi, 1967 w., III yriloba kisiniovsi, 1973 w., IV yriloba rigasi, 1974 w., V yriloba xarkovsi, 1980 w., VI yriloba kazansi, 1984 w. da sxva). profesor b. WumburiZes miacnda, rom codnas mxolod regionuli danisnuleba ki ara, saertasoriso mnisvneloba aqvs. amitomac miicnevda da dresac miicnevs, rom warmatebebis sawindari, dauralav SromasTan ertad, sxvisi codnis, gamocdilebis gaziareba da gaazrebaa. icoda, rom mecnierebasi karcaketiloba ar iyo gamartlebuli. amitomac ar sjerdeboda sabwota kavsiris masstabebs da aqtiurad monawileobda saertasoriso samecniero forumebsi (prara 1961w., leipcigi 1962w., budapesti 1962w., berlini 1963w., olomuci 1965w., belgradi 1967w., vena 2000w., parizi 2002w., nica 2002w., budapesti 2004w. da sxva). misi samecniero kvalifikaciis amarlebaze didi gavlena iqonia moskovisa da evropis umarles saganmanatleblo dawesebulebebsa Tu samecniero-kvlevit institutebsi gavlilma stajirebebma. bizina WumburiZis samecniero morvaweoba ukavsirdeba Cveni qveyanisa da ucxoetis iset cnobil samecniero centrebs, rogorebicaa: Terapiis, kardiologiis, mean-ginekologiis, izotopebis samecniero kvleviti, praris, budapestis, berlinis wamlis standartizaciisa da xarisxis kontrolis, moskovis farmakologiis, qimiur 22

23 farmacevtuli, polimerebis samecniero-kvleviti institutebi, moskovis samedicino universiteti da sxv. gansakutrebit saintereso da arnisvnis Rirsi bizina WumburiZis pedagogiuri saqmianoba gaxlavt. igi iyo da dremde rceba misabaz, studentebisatvis sayvarel leqtorad. misi yoveli leqcia siaxleebitaa gajerebuli. igi dajildovebulia oratoruli niwita da komunikaciis gansakutrebuli unarit. bunebit Semoqmedi, Rirseuli pedagogi, wlebis Semdegac leqciis win iseve emzadeba da Relavs TiTqos pirvelad unda warsdges auditoriis winase, amitomac aris igi mudam Tanamedroveobis motxovnebis simarleze. profesori b. WumburiZe dresac aqtiurad morvaweobs umarlesi ganatlebis samive safexurze. gansakutrebuli arnisvnis Rirsia misi xelmzrvanelobit Sedgenili samagistro saganmanatleblo programa farmacevtul analizsi, romelic motxovnadia da misive xelmzrvanelobit warmatebulad xorcieldeba. wlebis manzilze batoni bizina iyo sabwota kavsiris janmrtelobis dacvis saministros metodsabwos wevri, Tssu farmacevtuli fakultetis metodkomisiis Tavmjdomare, aqtiur monawileobda da monawileobs farmacevtta momzadebis saganmanatleblo programebis SedgenaSi. mis kalams ekutvnis qartul enaze Sedgenili da gamocemuli fundamenturi xasiatis saxelmzrvaneloebi, romlebic gamoiyeneba swavlebis samive doneze. profesori bizina WumburiZe aqtiuradaa CarTuli qartuli farmaciis, rogorc dargis, reformirebisa da regulirebis sakitxebsi. misi usualo monawileobita da xelmzrvanelobit momzadda kanoni wamlisa da farmacevtuli saqmianobis Sesaxeb, ara erti kanonqvemdebare aqti, farmacevtuli saqmianobis maregulirebeli sakanonmdeblo dokumentacia da sacnobaro literatura. gansakutrebit arsanisnavia misi TaosnobiT qartul enaze Sedgenili da gamocemuli saxelmwifo farmakopeis I da II tomebi. amjamad profesor bizina WumburiZis xelmzrvanelobit dasrulda orwliani musaoba axal kanonze wamlisa da farmacevtuli saqmianobis Sesaxeb. praqtikul farmaciaze misi zrunvis dadasturebaa is faqtic, rom wlebsi igi iyo saqartvelos janmrtelobis dacvis saministros mtavari specialisti-provizori. dres profesor bizina WumburiZis arzrdilebi warmatebulad morvaweoben rogorc umarles saganmanatleblo da samecniero dawesebulebebsi, aseve dargis maregulirebel organoebsa da praqtikul farmaciasi. Rvawlmosilma mecnierma Cveni qveynisatvis ert-ert umzimes periodsi SeZlo samsoblosatvis kidev ertxel gaewia Rirseuli samsaxuri wlis 9 aprilis tragediis Semdeg saqartvelos umarlesi sabwos prezidiumma swored mas miando qimiur-toqsikologiuri gamokvlevis komisiis Tavmjdomaris moadgileoba, romlis musaobasi aqtiurad CaerTvnen farmacevtuli qimiis katedris TanamSromlebic. komisiam udidesi Sroma gaswia, gamoavlina marali profesionalizmi da SeZlo daedgina momwamvlel nivtierebata, qloracetofenonisa da siesis, gamoyenebis faqti. daskvna moskovsi sabwota armiis mtavari toqsikologebis winase profesorma bizina WumburiZem warmatebulad daicva da komisiis mier mirebuli Sedegebi gamoqveynda kidec. kvlevis masalebma satanado adgili daikaves anatoli sobcakis cnobil moxsenebasi. arnisvnis Rirsia profesor bizina WumburiZis sazogadoebrivi saqmianoba wlidan igi saqartvelos farmacevtuli sazogadoebis ert-erti suliscamdgmeli da aqtiuri wevria; wlebsi iyo Tbilisis farmacevtta sazogadoebis Tavmjdomare, wlebsi ki vice-prezidenti wlidan profesori bizina WumburiZe saqartvelos farmacevtta asociaciis sapatio prezidenti, daarsebidan dremde sazogadoeba codnis aqtiuri leqtoria, ristvisac dajildovebulia vavilovis medlit da medlit aqtiuri morvaweobisatvis. misi nayofieri mecnieruli saqmianoba da mirweuli 23

24 warmatebebi arinisna saxelmwifos mier. igi aris saxelmwifo premiis laureati mecnierebisa da teqnikis dargsi da Rirsebis ordenis kavaleri. profesor bizina WumburiZis mier ganvlili gza aris ara marto erti qartvelis aramed, qartuli farmaciis mier ganvlili gza da misi uaxlesi istoriis mnisvnelovani nawili. mecnieri Tavis iubiles xvdeba SesaniSnav ojaxtan ertad, romelic misi yvelaze didi monapovaria. ojaxis Tanadgomis garese SeuZlebelia miarwio warmatebebs. meurle, qalbatoni rusudani, aseve cnobili mecnieria, Svilebic, vaxtangi da Tamazi, msoblebis kvals gahyvnen da TavianTi sityva Tqves qartul mecnierebasi. babuis Rurseul gzas SvivliSvilebi da SvilTaSvilebi agrzeleben, darwmunebuli vart isinic ityvian TavianT satqmels. profesori bizina WumburiZe dresac Cveuli ritmit agrzelebs samecniero-pedagogiur da sazogadoebriv morvaweobas. igi uangarod gadascems Tavis codnasa da gamocdilebas axalgazrdobas. sjera saqartvelos uketesi momavlisa da surs, rom warmatebuli qveynis moqalaqe iyos, man xom amasi Tavisi wili aguri ukve dado. qartuli farmacevtuli da samedicino sazogadoeba 2014 wlis 2 maiss, profesor bizina WumburiZis saxelovan iubiles, dabadebidan 90 wlistavs II saertasoriso samecniero konferenciit farmacevtuli mecnierebebi XXI saukunesi arnisnavs. es forumi misi samecniero da pedagogiuri saqmianobis Sedegi gaxlavt. batono bizina! gilocavt iubiles, gisurvebt janmrtelobas, didxans sicocxlesa da warmatebul morvaweobas Cveni erisa da qveynis saketildreod. farmaciis ganvitarebis istoriuli etapebi saqartvelosi WumburiZe b. Tbilisis saxelmwifo samedicino universiteti, saqartvelo qartul farmacias mravalsaukunovani, mdidari istoria da saxelovani tradiciebi aqvs. qartul epossi amiraniani, romelic Zveli weltarricxvis II ataswleuls ekutvnis, mititebulia mcenareebisa da mineraluri wylebis samkurnalo Tvisebebsa da mati gamoyenebis metodebze. saberznetsa da romsi Seiqmna mxatvruli da istoriuli nawarmoebebi argonavtebis mitis da kolxetis mefis aietis qalisvilis medeas Temaze. XIII-XII saukuneebsi Cven weltarricxvamde, kolxetsa da iberiasi medicina sakmaod maral doneze idga. icnobdnen samkurnalo sasualebebs da eweodnen samkurnalo mcenareebis mosenebas. kolxetis mefis aietis dis hekates da qalisvilis - medeas saxeltanaa dakavsirebuli yvelaze adreuli mititeba sisxlis gadasxmis da gaaxalgazrdavebis Sesaxeb. kolxeti da iberia momdevno saukuneebsic cnobili iyo, rogorc unikaluri samkurnalo sasualebebis da Sxamebis mcodne mxare (mixeil Sengelia). saqveynod aris cnobili pontos mefis mitridate pontoelis (Zv.welTaR ww.) Sxamebi da imuniteti, romelic man gamoimusava sakutar organizmsi, mowamvlisagan Tavdacvis miznit. mitridatem SemoiRo fartod cnobili samkurnalo sasualeba 24

25 mitridatumi, igi mravali saukunis ganmavlobasi mzaddeboda da fartod gamoiyeneboda mtel evropasi. Zveli weltarricxvis VI-saukunidan axali weltarricxvis V-saukunemde saqartvelosi qristianul tazrebsi samedicino saqmianobas eweodnen ara mxolod religiur-magiuri ritualebit, agretve racionaluri samkurnalo sasualebebit. adrefeodalur saqartvelosi (V-Xs.s) vitardeba medicina.samkurnalo saqmianobas ewevian:qartuli samonastro tazrebsi qartuli lavra sabawminda, Sio mrvime, xanztis savane, varziis da vanistavis monastrebi. samkurnalo da samedicino literaturul saqmianobas eweodnen gamocenili morvaweebi: martvili sabawmindeli (VII s), ioane zedazneli, abibo nekreseli, Sio mrvimeli (VI s.), ilarion qartveli (IXs), grigol da epifane xanztelebi (VIII-IXs.s.) da sxvebi. saqartvelos medicinis istoriasi gansakutrebuli adgili ukavia klasikur xanas (XI - XIIIs.s.), am periodsi gelatis da iyaltos akademiebsi Seiqmna mecnieruli da praqtikuli medicinis da farmaciis RirsSesaniSnavi werilobiti Zeglebi: qananelis _ usworo karabadini, xojatyofelis wigni saaqimo. am wignebsi SesaZloa ipovot saintereso cnebebi anatomiisa da fiziologiis, higienis, Terapiisa da samkurnalo sasualebata Sesaxeb; gansakutrebit fartod aris warmodgenili wamlis formebi, am cnobebis sizuste gancvifrebas iwvevs da bevri ram momavali kvlevis sagania. gelatis monastertan iyo saavadmyofo da wamaltxana, akademiasi aswavlidnen medicinas, maswavleblebad iyvnen ioane petriwi da arsen iyaltoeli. SoTa rustavelis genialur poemasi _ vefxistyaosani aris gamotqmebi, romlebic cxadyofs, rom avtori erkveva samedicino sakitxebsi (m. Sengelia). X saukunidan qartvelebi saberznetsi, atonis iveris monastersi did samkurnalo da farmacevtul saqmianobas eweodnen. qartul samedicino mecnierebis da wamaltmcodneobis armavloba grzeldeboda monrolebis Semosevamde. monrolebis Semosevam (XII saukunesi) dasala saqartvelos saxelmwifos ertianoba. daingra qveynis kulturul-saganmanatleblo centrebi. miuxedavad mzime ekonomikuri mdgomareobisa, XVI saukunis dasawyisidan saqartvelos sazogadoebis mowinave nawilma SesZlo aredgina medicina da wamaltmcodneoba. saqartvelos arorzinebis xanis umnisvnelovanesi samedicino Zeglebia zaza fanaskertelis samkurnalo wigni da davit batonisvilis iadigar daudi. CamoTvlili wignebi unikaluri Zeglebia qartuli medicinis da farmaciis istoriisa. XVII-XVIII saukunesi saqartvelosi farmacevtuli saqmianobis arorzinebas xeli Seuwyes katolike misionerebma. mat 1740 wels TbilisSi gaxsnes aftiaqi e.w. wamalt-xana. nacionaluri samedicino kadrebis aryolam gamoiwvia ucxoetidan, kerzod, evropidan wamaltmcodne specialistebis mowvwvis aucilebloba. wamaltmcodneobas did yuradrebas aqcevda mefe erekle II, mis dros gaixsna samedicino skola. dampyrobta ganuwyvetelma Semosevebma qartuli saxelmwifo daangria.mecniereba, mat Soris medicina da wamaltmcodneoba degradirebuli iqna wels TbilisSi gaixsna pirveli saxelmwifo aftiaqi, moewyo specialuri bari samkurnalo mcenareta mosaseneblad. aftiaqtan moewyo laboratoria adgilobrivi nedleulidan wamlebis mosamzadeblad. 25

26 pirveli samkurnalo dawesebuleba stacionarit da aftiaqit TbilisSi gaixsna 1808 wels wels Serbergma gaxsna aftiaqi wamlis Tavisufali gayidvis uflebit wels TbilisSi gaixsna meore aftiaqi. XIX saukunis 60-ian wlebsi iwyeba aftiaqebis gaxsna saqartvelos qalaqebsi wels saqartvelosi funqcionirebda 23 aftiaqi wels 63 aftiaqi, xolo 1914 wels 161 aftiaqi. am dros samkurnalo sasualebani ZiriTadad ucxoetidan Semodioda wels Camoyalibda jandacvis saxalxo komisariati, romelmac Caatara aftiaqebis nacionalizacia. jandacvis komisariatsi Seiqmna farmacevtuli ganyofileba wels samkurnalo sasualebata uzrunvelyofistvis organizebuli iqna saxmedvawroba wels Tbilisis saxelmwifo universitetis samedicino fakultettan Seiqmna farmacevtuli ganyofileba. xolo 1937 wels Camoyalibda Tbilisis saxelmwifo farmacevtuli instituti, profiluri katedrebit: farmacevtuli qimiis, wamalta teqnologiis, farmakognoziis, farmacevtuli saqmis organizaciis. institutis direqtori iyo prof. iovel qutatelaze, direqtoris moadgile prof. pavle WumburiZe. amjamad Tbilisis saxelmwifo samedicino universitetsi ert-erti fakultetia farmaciis fakulteti. am fakultetma gadawyvita saqartvelosi umarlesi ganatlebis farmacevtuli kadrebis momzadebis problema. arzarda mecnieruli da praqtikuli kadrebis mravali Taoba. saqartvelos farmacevtuli ganatlebis, kadrebis arzrdis, mecnierebis Casaxvis ganvitarebis sataveebtan idgnen Cveni gamocenili maswavleblebi: akademikosi iovel qutatelaze, profesorebi: nikoloz masxulia, pavle WumburiZe, valerian SoTaZe da aristarx msvidobaze, mati da mati mowafeebis Tavdadebuli Sromis nayofia, rom qartuli farmacevtuli dargi aertianebs asze met mecnierebata doqtors, profesors, ramodenime atas farmacevts da farmacevtis TanaSemwes wels qutaisis akaki weretlis saxelmwifo universitettan, xolo 2009 wels batumis SoTa rustavelis saxelobis saxelmwifo universitetsi gaixsna farmaciis ganyofileba wels Camoyalibda akademiis farmakoqimiis instituti, romelic misi damaarseblis, iovel qutatelazis saxels atarebs. instituti nayofier samecniero-kvlevit musaobas eweoda da eweva saqartvelos samkurnalo mcenareta gamovlinebisa da Seswavlis saqmesi. am samecniero centris Camoyalibebis iniciatorebi da organozatorebi iyvnen akademikosi iovel qutatelaze da profesori aristarx msvidobaze. iovel qutatelazem, nikoloz masxuliam, pavle WumburiZem, valerian SoTaZem, aristarx msvidobazem, qetevan mujirma da matma TanamSromlebma jer kidev samamulo omis dawyebamde gamoikvlies, daamusaves da mrewvwlobasi danerges axali samkurnali preparatebi: digalen-neo, periplocini, filikoli, satiturani, sukradbeli, Tealbini, elargoli da sxva. am preparatebis eqsperimentuli da klinikuri gamokvlevebi Catarda cnobili qartveli medikosebis: dimitri gedevanisvilis, grigol gvisianis, aleqsandre aladasvilis, mixeil winamzrvrisvilis, nikoloz yifsizis xelmzrvanelobit. didi samamulo omis wlebsi, institutis laboratoriebsi kavkasiis frontisatvis mzaddeboda wamlebi, romelic kavkasiis fronts miewodeboda wlebis samamulo omsi gawveuli iqna farmacevtuli institutis kursdamtavrebulni da aspirantebi. qartvelma farmacevtebma Rirseulad Seasrules movaleoba samsoblos winase. bevri matganis wvlili da damsaxureba ordenebita da medlebit iqna arnisnuli. 26

27 samedicino institutis farmaciis fakultetis profesor-maswavleblebis mier 60-ian wlebsi gamocemuli iqna saswavlo da samecniero literatura:iovel qutatelazis analizuri qimia da farmacevtuli terminologia, vladimer asatianis monografiebi da bioqimiuri analizis metodta krebulebi, aristrax msvidobazis farmacevtuli qimia saxelmzrvanelo, valerian SoTaZis farmakognozia, bizina WumburiZis wamalta analizis fizikur-qimiuri metodebi da ionmcvleli polimerebis gamokvleva, lina eristavis, grigol CixlaZis, kote sandomisasvilis monografiebi da sxva. 70-ian wlebsi gamoica simpoziumis masalebi qromatografiuli metodebi farmaciasi, farmacevtta I yrilobis masalebi, samecniero Sromebis krebuli da sxva. ukanaskneli wlebis ganmavlobasi gamoqveynda ramodenime aseuli samecniero Sroma, matgan ramodenime ucxoetsi. samociani wlebidan dawyebuli, farmacevtuli sazogadoebis mowinave warmomadgenlebi monawileobas Rebuloben-saerTaSoriso samecniero forumebsi evropis qveynebsi. farmacevtuli warmoebis Canasaxad saqartvelosi unda CaiTvalos galenur-safasovo laboratoria saaftiaqo sammartvelos centralur sawyobtan, romelic 1924 wels moewyo wels arnisnuli laboratoriis bazaze daiwyo farmacevtuli qarxnis msenebloba wels arnisnuli farmacevtuli qarxana gadaeca samrewvelo gaertianebas farmqimmrewvi wels saqartvelosi amoqmedda batumis kofeinis qarxana, xolo 1942 wlidan mwyobrsi Cadga organoterapiuli preparatebis qarxana. XX saukunis 30-iani wlebidan TbilisSi funqcionirebs vaqcinebisa da Sratebis samecnierokvleviti instituti da Seasabamisi sawarmo. garda arnisnuli sawarmoebisa, saqartvelosi aris qobuletis da Suaxorgis samkurnalo mcenareta meurneobebi, romlebic im droisatvis mcenareuli nedleulit amarageben farmacevtul sawarmoebs. saqartvelos damoukidebel saxelmwifod Camoyalibebis Semdeg swrafad ganvitarda farmacevtuli mrewveloba. dresdreisobit wamyvani farmacevtuli sawarmoebia: GMP, aversi-racionali, neofarmi, Tbilqimfarmi da sxvebi. qartuli farmacevtuli sawarmoebi 500-ze met farmacevtul preparats awarmoebs seriulad. saqartvelosi farmacevtuli mrewvelobis ganvitarebis saqmesi amjamad mnisvnelovani wvlili SeaqvT: profesor aliosa bakurizes, giorgi antazes da giorgi datukisvils wels daarsda saqartvelos farmacevtta sazogadoeba, romlis prezidentad arceuli iqna akademikosi iovel qutatelaze. vice-prezidentad profesori aristarx msvidobaze, swavlul mdivnad grigol CixlaZe. erti Tvis Semdeg daarsda Tbilisis farmacevtuli sazogadoeba wlis ganmavlobasi daarsda farmacevtuli sazogadoebebi qutaissi, soxumsi, batumsi da gurjaansi wlebsi sazogadoebebi daarsda ozurgetsi, gorsi, TelavSi, rustavsi da zugdidsi. saqartvelos farmacevtta sazogadoebis wesdebis proeqti Seadgina prof. aristarx msvidobazem da prof. bizina WumburiZem. farmacevtuli sazogadoebis wesdeba upiratesad itvaliswinebda farmacevtuli kadrebis kvalifikaciis amarlebas da daxelovnebas; farmacevtuli dawesebulebebis materialur-teqnikuri bazis gaumjobesebis xelsewyobas; samkurnalo sasualebebit mosaxleobis uzrunvelyofis gaumjobesebas; farmacevtuli momsaxurebis kulturis amarlebas; sazogadoebis wevrta uflebebis dacvas; Sromis mecnieruli donis amarlebas; wamlebis xarisxis gaumjobesebas; farmacevtuli mrewvelobis gafartoebas da mecnieruli farmaciis ganvitarebas. XX saukunis samociani wlebis dasawyisidan, gaaqtiurda kavsirebi evropis qveynebtan, SesaZlebeli gaxda evropis qveynebis da saertasoriso samecniero konferenciebsi da 27

28 kongresebsi monawileoba. ucxo qveynebis mecnierebtan saqmianma kontaqtebma, xeli Seuwyo farmacevtuli mecnierebis da praqtikis ganvitarebas. XX saukunis samocdaatian wlebsi kidev ufro gafartovda kontaqtebi ucxo qveynebis mecnierebtan da samecniero dawesebulebebtan. praqtikasi Semovida mivlinebebi gamocdilebata gaziarebis miznit, axali metodebis atvisebisatvis. ai is RonisZiebani, romelsic farmacevtuli sazogadoeba did rols asrulebda. samocdaatiani wlebis meore naxevridan da otxmocian wlebsi daiwyo sakavsiro da saertasoriso konferenciebis mowyoba TbilisSi. am periodsi yovelwliurad ramdenime ateulma axalgazrdam daicva disertacia. qveyndeboda mecnieruli Sromebi, istambeboda saxelmzrvaneloebi, monografiebi, SromaTa krebulebi. mecniereba prioritetuli gaxda,mecnierebi dafasebulebi iyvnen da amitom didi iyo ltolva mecnierebisadmi. winaprebisa da tradiciebisadmi pativiscema sapatio saqme iyo. gansakutrebulad arinisneboda mecnierebisa da damsaxurebuli morvaweebis iubileebi, mogonebebis saramoebi, dafasebuli iyo winaparta Rvawli da Tavdadeba samsoblos winase. saqartvelos farmacevtul sazogadoebasi Rrma kvali datova qalaqebsa da regionebsi gamsvleli samecniero sesiebis mowyobis farto praqtikam wlidan 1980 wlamde yovelwliurad ewyoboda gamsvleli samecniero sesiebi. am sesiebze ketdeboda moxsenebebi, rogorc mecnier-musakebis, agretve saaფtiaqo sammartvelos xelmzrvanelebis da aftiaqis TanamSromlebis mier. arnisnuli sesiebi profesiul ZalTa namdvili datvaliereba iyo.am RonisZiebebSi aqtiurad monawileobdnen: iovel qutatelaze, aristarx msvidobaze, petre gelbaxiani, bizina WumburiZe, lina eristavi, eter qemertelize, qetevan mujiri, levan CxataraSvili, viqtor bostoranasvili, guram cagareisvili, valentina vacnaze, otar nisnianize, kote sandomisasvili, mixeil WiWinaZe, varden sefiasvili, grigol CixlaZe, roman maxaraze, vaja eriasvili, simon ujmajurize, viqtor dgebuaze, aliosa bakurize, nodar zabaxize, davit WinWaraZe, rezo sxilaze da sxvebi wels TbilisSi moewyo samecniero konferencia samkurnalo mcenareebis sakitxebze wels TbilisSi moewyo simpoziumi qromatografiuli metodebi farmaciasi, simpoziumsi monawileobdnen cnobili qromatografistebi ucxo qveynebidan. gamoica simpoziumis masalebi. am RonisZiebasTan dakavsirebit sabwota kavsiris mecnierebata akademiam bizina WumburiZe daajildiva sapatio sigelit qromatografiis ganvitarebisatvis kacobriobis saketildreod wels TbilisSi Catarda saqartvelos farmacevtta I yriloba. yrilobis musaobasi monawileoba miiro yvela respublikis delegaciam. gamoica yrilobis masalebi wels TbilisSi Catarda sakavsiro samecniero konferencia farmakokinetikis sakitxebze. masalebi daistamba or tomad. samecniero farmacevtuli sazogadoebis saqmianobis mirwevad unda CaiTvalos saxelmzrvaneloebis, monografiebis da wignebis gamocemebi. am mxriv arsanisnavia: iovel qutatelazis, vladimer asatianis, aristarx msvidobazis, petre gelbaxianis, bizina WumburiZis, roman maxarazis,vaja eriasvilis, aliosa bakurizis, lina eristavis, eter qemertelizis, guram cagareisvilis, nodar zabaxizis, vladimer maxarazis da sxvebis publikaciebi. 28

29 gasuli saukunis 90-iani wlebidan farmacevtta samecniero sazogadoebas kidev erti sazrunavi gaucnda farmacevtuli sferos kanonebis da kanonqvemdebare aqtebis proeqtebis Sedgena-ganxilva. arnisnuli sakanonmdeblo aqtebi SemuSavda, ganxiluli iqna, damtkicda parlamentis mier. amis Semdgom wlebsi daiwyo matsi ganuwyveteli cvlilebebis Setana. es procesi dresac grzeldeba. saqartvelosi, farmacevtuli kadrebis momzadebis da mati profesiuli daxelovnebis saqmesi amjamad reforma mimdinareobs. farmaciasi dainerga samsafexuriani saganmanatleblo sistema. es sistema moicavs: bakalavriats, magistraturas da doqturanturas. XX saukunis meore naxevarsi saqartvelos samecniero-farmacevtulma asociaciam didi roli Seasrula mecnieruli da praqtikuli farmaciis ganvitarebasi, es gansakutrebit gamoixata kadrebis momzadebasa da mat profesiul daxelovnebasi; jandacvis msoflio organizaciasa da saertasoriso farmacevtul sazogadoebebtan kavsirebis CamoyalibebaSi: yovelive aman gaamtliana Cveni sazogadoeba qveynis SigniT da agretve daamyara kavsirebi saertasoriso masstabit. es periodi gansakutrebuli muxtis matarebeli iyo. amjamad saqartvelos farmacevtuli dargis winase ramodenime problema dgas, aucilebelia: - Seiqmnas da amoqmeddes samkurnalo sasualebata xarisxis uzrunvelyofis saxelmwifo sistema; - ardges da dakanondes, rom farmacia regulirebadi profesiaa; - amoqmeddes receptis instituti; - mowesrigdes farmacevtuli samsaxuris saxelmwifo sistema; - daregulirdes wamlis fas-warmoqmna, evropis qveynebis magalitze; - ardges da amoqmeddes antimonopoliuri kanoni; - daarsdes wamlis xarisxis kontrolis saarbitrajo laboratoria; - amoqmeddes wamlis monitoringis samsaxuri. saqartvelosi wamlis registracia unda uzrunvelyofdes mis xarisxs, efeqturobas da usafrtxoobas. farmacevtta saertasoriso organizaciebtan da ucxo qveynebis farmacevtul sazogadoebebtan urtiertoba 1960 wlidan ganaxlda. Cexoslovakiis farmacevtta yrilobasi monawileoba 1961 wels axali era iyo qartvel farmacevtta cxovrebasi wels leipcigsi, germaniis farmacevtta yrilobasi monawileoba; budapestsi mivlineba gamocdilebia gaziarebis miznit, 1962 wels. mivlineba iaponiasi 1966 wels. monawileoba iugoslaviis farmacevtta yrilobis musaobasi da a.s. italiasi 1970w. ass. 1975w. indoetsi 1985w. saberznetsi 1987w. avstriasi 2000w.farmacevtTame-60kongresze saqartvelos delegacia soliduri iyo: prof. amiran gamyrelize, prof. bizina WumburiZe, prof. roman maxaraze, prof. T. WumburiZe, a. TomaZe, m. giorgobiani da sxvebi. safrangetsi (nica) ki qartuli delegacia sami kacisgan Sedgeboda: prof. bizina WumburiZe, prof. T. WumburiZe da davit kilaze. XX saukunis 60-ian da samocdaatian wlebsi evropis qveynebis farmacevtul sazogadoebata samecniero forumebsi monawileobdnen lina eristavi da bizina WumburiZe. XX saukunis otxmocdaatian wlebsi damyarda urtiertoba jandacvis msoflio organizaciastan da misi evropis regionalur organizaciastan. ewyoboda seminarebi, TaTbirebi, mivlinebebi gamocdilebis gaziarebis miznit. aseti RonisZiebebi moewyo evropis qalaqebsi: kopenhagensi, budapestsi, berlinsi, milansi, prarasi, londonsi, JenevaSi, venasi, varsavasi da sxvagan. xutjer moewyo saertasoriso kongresi TbilisSi, devizit: janmrteloba da wamali. saorganizacio komitetis wevrebi iyvnen roman maxaraze da aliosa bakurize. TbilisSi 29

30 2002 wels moewyo farmacevtta saertasoriso kongresi. am kongresze Tbilisis farmacevtta organizaciis wevrta ramdenime moxseneba iqna gaketebuli: eter qemertelizis, bizina WumburiZis, aliosa bakurizis, Tamaz WumburiZis da aleqsandre TomaZis mier wlidan dremde saqmiani urtiertoba gvaqvs evropis farmakopeis komitetetan. bizina WumburiZe aris evropis farmakopeis komitetis eqsperti wels Tamaz WumburiZe arceuli iqna jandacvis msoflio organizaciis evrofarmforumis asableis wevrad. saamayoa rom jandacvis msoflio organizaciis evropis regionis direqtoris moadgile aris samedicino universitetis farmacevtuli fakultetis arzrdili nata menabde. farmacevtta asociaciis prezidenti aris batumis universitetis reqtori profesori aliosa bakurize. samecniero-semoqmedebiti urtiertoba gvaqvs marselis, xmeltasuazrvis, liejis, lublianis, kvebekis, bolus, xarkovis da sxva universitetebtan. gasuli saukunis 90-iani wlebis dasawyissi, dris wesrigsi dadga farmaciasi saxelmwifo reformis gatareba. ministrta sabwos dadgenilebit, 1991 wels Camoyalibda samkurnalo sasualebebis, kvebis produqtebisa da axali teqnologiebis sertifikaciis komiteti, romelic 1994 wels gadaketda farmakologiur komitetad, moxda saaftiaqo sammartvelos reorganizacia; farmacevtuli dawesebulebebis privatizacia; farmakologiuri da farmakopeuli komitetebis Camoyalibeba; Seiqmna wamlisa da farmacevtuli saqmianobis departamenti; farmacevtuli saqmianobis makontrolebeli inspeqcia, wamlis xarisxis makontrolebeli saxelmwifo laboratoria. avtonomiuri respublikebisa da regionebis farmacevtuli saqmianobis maregulirebeli struqturebi. amjamad, arnisnuli struqturebi gaertianebulia jandacvis saministros samedicino saqmianobis maregulirebel departamentsi. farmaciis departamenti ki ar arsebobs. reforma Seexo farmacevtul samrewvelo sawarmoebs da mrewvelobis nedleulis meurneobebs, moxda mati privatizacia. Seiqmna samedicino da farmacevtuli kadrebis diplomissemdgomi sertificirebis sistema, farmacevtuli dawesebilebebis licenzirebis samsaxurebi. saqartvelos farmacevtta asociaciis prezidiumma, saqartvelos janmrtelobis dacvis saministros xelmzrvanelobastan da saqartvelos parlamentis janmrtelobisa da socialuri dacvis komitettan ertad moamzada kanonebi: wamlisa da farmacevtuli saqmianobis Sesaxeb, samedicino kadrebis uwyveti mzadebis Sesaxeb, speckontrols daqvemdebarebul samkurnalo sasualebata mimoqcevis Sesaxeb, samedicino dafarmacevtul dawesebulebata licenzirebis Sesaxeb. garda zemoarnisnuli kanonebisa, didi musaoba Catarda farmacevtta sertificirebis kanonsa da wesebze. kolosaluri samusao ikisres da warmatebiთ Seasrules Tbilisis saxelmwifo samedicino universitetis farmacevtuli fakultetis profiluri katedrebis profesor- maswavleblebma. es aris sasertifikacio gamocdebis testkitxvarebis Sedgena, ganxilva, damtkiceba da dastambva. farmacevtuli saqmianobis maregulirebel kanonebs Sesabamisi kanonqvemdebare aqtebi esawiroeba. Sedgenili, ganxiluli, damtkicebuli da dastambulia ormocdatormetamde kanonqvemdebare aqti. 30

31 Tbilisis samedicino universitetis farmaciis fakultetis departamentebi farmacevtuli da toqsikologiuri qimiis departamenti farmacevtuli qimiis katedra 1921 wels Seiqmna Tbilisis saxelmwifo universitetsi wlamde katedras ganagebda profesori iovel qutatelaze. katedraze pirvel wlebsi musaobdnen nikoloz masxulia da pavle WumburiZe wlidan 1942 wlamde katedras xelmzrvanelobda profesori nikoloz masxulia wlidan 1973 wlamde katedris gamge iyo profesori aristarx msvidobaze wlidan 1996 wlamde katedras xelmzrvanelobda mediko-biologiuri da samedicino-socialur mecnierebata akademiebis akademikosi, profesori bizina WumburiZe wlidan farmacevtuli da toqsikologiuri qimiis departamentis xelmzrvanelia samedicino mecnierebata akademiis akademikosi, profesori roman maxaraze. sxvadasxva dros farmacevtuli da toqsikologiuri qimiis katedraze pedagogiur saqmianobas eweodnen: aristarx msvidobaze, nino JRenti, irina enuqize, olia sarjvelaze, pavle WumburiZe, luba esebua, qetevan mujiri, nunu iobasvili, klara gamsaxurdia, SoTa Rlonti, irakli natrosvili, simon ujmajurize, nazi surmava, QqeTevan baramize, maia QqurcikiZe da sxvebi. amjamad departamentsi pedagogiur saqmianobas ewevian: bizina WumburiZe, roman maxaraze, lia adeisvili, Tamaz murtazasvili, madona jorjikia, luiza kunwulia, naili SengeliZe, Tamar CikvilaZe, nino imnaze, hilda ioramasvili, Tamar otarasvili, nino nijaraze, nana lekisvili da Tamar muzasvili. katedris bazaze mzaddeba magistrebi farmacevtul analizsi, samagistro programas xelmzrvanelobs profesori bizina WumburiZe. katedraze didi musaoba mimdinareobs saswavlo saxelmzrvaneloebis momzadebagamocemis saqmesi. am mxriv gansakutrebit arsanisnavia aristarx msvidobazis, bizina WumburiZis, roman maxarazis, lia adeisvilis da sxvebis gamocemebi. farmacevtuli qimiis saxelmzrvanelos gamocemisatvis bizina WumburiZes mieniwa saxelmwifo premia mecnierebisa da teqnikis dargsi. katedris TanamSromlebi mnisvnelovan samecniero-kvlevit musaobas eweodnen da ewevian. mat mier Sesrulebuli da daculia 30-ze meti disertacia, mirebulia 25-ze meti gamogonebis saavtoro mowmoba. gamoqveynebulia ramodenime aseuli mecnieruli Sroma, ramodenime monografia, konferenciis masalebi, SromaTa krebulebi da sxva. Camoyalibebulia da moqmedebs ramodenime mecnieruli skola-mimartuleba: - samkurnalo sasualebata standartizacia; - wamalta analizis qromatografiuli metodebi; - narkologiur-toqsikologiuri analizi; - farmakokinetikuri kvleva. katedra aqtiurad monawileobs farmaciis kanonebis proeqtebis Sedgena-ganxilvaSi. farmacevtuli teqnologiis departamenti farmacevtuli teqnologiis departamenti daarsda 1935 wels `wamalta da galenuri preparatebis teqnologiis katedris saxelwodebit wels mas ewoda `wamalta teqnologiis katedra, xolo 2004 wels `farmacevtuli teqnologiis katedra saswavlo wlidan katedras ewodeba farmacevtuli teqnologiis departamenti. 31

32 wlebsi katedris gamge iyo irakli burjanaze, wlebsi profesori petre gelbaxiani, wlebsi docenti levan CxataraSvili, wlebsi docenti ipolite moniava, 2000 wlidan departamentis xelmzrvanelia samedicino mecnierebata akademiis akademokisi, profesori aliosa bakurize. katedraze sxvadasxva wlebsi musaobdnen profesorebi: pavle WumburiZe, petre gelbaxiani, aristarx msvidobaze; docentebi: irakli burjanaze, samson asatiani, levan CxataraSvili, revaz sxilaze, nargiza sartania, Tina dolaberize, mariam trapaize, grigol CixlaZe, jemal enuqize,lleila kereselize, nazi RuduSauri; pedagogebi: v. vilareti, Tamar bejanisvili, revaz murrulia, guram woworia. departamentsi iswavleba Semdegi disciplinebi: `galenuri preparatebis teqnologia, `mza wamaltformebis teqnologia, `bunebrivi da sintezuri preparatebis teqnologia, `biofarmacia, `bioteqnologia, `kosmetikuri da parfiumeruli sasualebebis teqnologia, `homeipatiuri da veterinaruli sasualebebis teqnologia, `procesebi da manqana-aparatura farmacevtul mrewvelobasi. amjamad departamentsi pedagogiur saqmianobas ewevian:aliosa bakurize,ipolite moniava, gulnara miqaia, jemal futkaraze, ia wurwumia, nino qurdiani, nino cagareisvili da lasa bakurize. farmacevtuli teqnologiis departamentis ZiriTadi samecniero mimartulebaa bunebrivi nedleulis gadamusavebis resursdamzogavi teqnologiebis SemuSaveba da mat bazaze Tanamedrove wamaltformebis momzadeba.departamentis TanamSromlebis aqtiur samecniero saqmianobaze metyvelebs is, rom gamoqveynebulia aseulobit samecniero statia, monografiebi, saxelmzrvaneloebi da mirebulia 50-ze meti patenti wlidan dremde katedraze Sesrulebulia da daculia 2 sadoqtoro da 17 sakandidato disertacia. dreisatvis departamentsi sruldeba 3 sadoqtoro programa. socialuri da klinikuri farmaciis departamenti farmacevtuli saqmis organizacia da istoria 1926 wlidan iswavleboda Tbilisis universitetis samkurnalo fakultetis farmaciisa da farmakognoziis katedraze(gamge _ farmaciis magistri eduard aboli). katedras wlebsi xelmzrvanelobda profesori petre gelbaxiani wlidan 1990 wlamde katedras xelmzrvanelobda docent l. CxataraSvili wels wamalta teqnologiis katedra gaiyo orad da Camoyalibda farmacevtuli saqmis organizaciis da ekonomikis katedra, gamged dainisna docenti levan CxataraSvili 1992 wlamde, xolo wlebsi katedris gamged danisnuli iyo profesori guram cagareisvili wlidan dremde katedras xelmzrvanelobs samedicino-socialur mecnierebata akademiis akademikosi, profesori vaja eriasvili wels katedras ewoda socialuri da klinikuri farmaciis katedra, xolo 2006 wlidan ki socialuri da klinikuri farmaciis departamenti. katedraze morvaweobdnen: g. CixlaZe, p. geleisvili, r. sxilaze.b. boworisvili, j. enuqize, i. murrulia da sxvebi. departamentsi iswavleba farmacevtuli saqmianobis organizacia, ekonomika da istoria, klinikuri farmacia, menejmenti da marketingi, saqonelmcodneoba, farmacevtuli biznesis safuzvlebi, informacia da kompiuteruli teqnologiebi wlidan v. eriasvilis xelmzrvanelobit moqmedebs samagistro programa: `farmaciis menejmenti da xdeba doqtorantebis momzadeba. samecniero musaobis ZiriTadi mimartulebebia: `samkurnalo sasualebebis farmakoekonomikuri da marketinguli gamokvleva, `farmacevtuli saqmianobis menejmenti, `wamaltmcodneobis bibliuri safuzvlebi da sxva. 32

33 amjamad departamentis akademiuri personalia: - vaja eriasvili _interkontinentaluri samedicino - socialur mecnierebata akademiis akademikosi, profesori, - Tamaz WumburiZe _ asocirebuli profesori, - nana gorgaslize - asocirebuli profesori - nino nemsiwverize _asistent-profesori; - Tea zarqua _asistent-profesori; - natia kvijinaze _ asistent-profesori; - nanuli durasvili - asistent-profesori; - mowveuli akademiuri doqtori: neli nikuraze; pedagogebi: Salva grzelisvili, soso TomaZe, nana iamanize, nino baxtaze, ekaterine fruize. TanamSromelTa mier wlebsi gamocemuli iqna 8 saxelmzrvanelo: 1. socialuri farmacia (avtori da redaqtori v. eriasvili, Tanaavtorebi: n. gorgaslize, S.grZeliSvili, T. zarqua, i. murrulia, n. nikuraze, g. papasvili). 2. farmacevtuli bazris ekonomikis leqsikoni (avtorebi: n. gorgaslize). 3. farmacevtuli biznesis safuzvlebi. (avtorebi: v. eriasvili, n. durasvili). 4. klinikuri farmacia. (avtorebi: T. WumburiZe, T. kikalisvili). 5. samedicino da farmacevtuli saqonelmcodneoba. (avtori: S. grzelisvili). 6. farmacevtuli saqmianobis menejmenti. (avtori: n. nemsiwverize). 7. farmacevtuli marketingis safuzvlebi. (avtorebi: T. zarqua, v. eriasvili). 8. wamalta standartizacia da xarisxis menejmenti. (avtorebi: b. WumburiZe, T. WumburiZe, T. CikvilaZe). farmakognoziisa da botanikis departamenti farmaciisa da farmakognoziis katedra daarsda 1921 wels Tbilisis saxelmwifo universitetis bazaze Seqmnil farmacevtul ganyofilebasi. misi pirveli xelmzrvaneli iyo akademikosi iovel qutatelaze ( ) wlidan farmakognoziis katedra calke erteulad gaxda, romelsac farmacevtuli da samedicino institutebis daqvemdebarebasi xelmzrvanelobdnen profesori eduard aboli ( ), profesori valerian SoTaZe ( ), profesori lina eristavi ( ), jumber kuwuxize ( ), 2013 wlidan departaments xelmzrvanelobs profesori davit WinWaraZe wlidan farmakognoziis katedras SeuerTa botanikis kursi, romelic farmacevtuli institutis Camoyalibebis Semdeg gardaiqmna botanikis katedrad, xolo 1953 wlidan kursis saxit kvlav SeuerTda farmakognoziis katedras. farmakognoziis katedraze sxvadasxva dros morvaweobdnen gamocenili mecnierebi da pedagogebi: farmaciis magistri konstantine baxtaze, prof. zaqaria yancaveli, akad. dimitri sosnovski, prof. Tamar kezeli, docentebi: maia baqraze, Tamar kacuxasvili, darejan kavsakize-virsalaze, lia kvitaisvili, murman nijaraze. ufrosi maswavlebeli nadia gavaseli, asistent- profesori maia qurcikize da sxva. amjamad, departamenti dakompleqtebulia Semdegi akademiuri personalit: - jumber kuwuxize sruli profesori; - davit WinWaraZe sruli profesori; - dali berasvili asocirebuli profesori; - malxaz joxaze asocirebuli profesori; - lasa msxilaze asistent-profesori; - ana bojaze _ asistent-profesori; mowveuli pedagogebi: manana maisasvili, lali zardiasvili. katedraze saswavlo procestan ertad warmatebit mimdinareobs samecniero kvleviti samusaoebi. mecnieruli kvlevis ZiriTadi mimartuleba iyo da amjamadac rceba 33

34 saqartvelos floris mcenareta Zieba axali samkurnalwamlo sasualebebis Seqmnis miznit wlebsi dafinansda wardgenili sagranto samecniero proeqtebi wels gamoica prof. lina eristavis saxelmzrvanelo farmakognoziasi, xolo 2012 wels jumber kuwuxizisa da malxaz joxazis avtorobit saxelmzrvanelo botanikasi farmaciis studentebisatvis. HISTORICAL STAGES IN THE DEVELOPMENT OF PHARMACY IN GEORGIA Chumburidze B. Tbilisi State Medical University, Georgia Georgian Pharmacy hasa rich history of many centuries and the renowned traditions. In Georgian Epos,,Amiraniani, belonging to the second millennium BC, is already mentioned about the curative properties of medicinal plants and mineral waters and the methods of their usage. The works of art and history on the Argonauts mythos and Medea, a daughter of the Kolkhetian ruleraiet,havebeen created in Greece and Rome. In XIII-XII centuries BC in Kolchis and Iberiathe medicine was quite well developed. Remedies were known and medicinal plants were cultivated. The earliest indication about the blood transmission and rejuvenation is related to the names of Hekate,a sister of the Kolchis ruler and Medea. Kolchis and Iberia were well known as unique lands of medicinal remedies and poisons (Mikheil Shengelia). Poisons and immunity of Mitridate Pontoeli, the King of Pontos ( BC),which he used to receive himself, in order to be protected from poisoning, is also well known. Mitridate has introduced a well-known remedy Mithridatum, which was used in whole Europe during many centures. Since VI century BC till V century AD in Georgian Christian Churches medicinal activity had been in progress as the religious-magic rituals, as well as by rational medicinal remedies. The Medicine was developed in early-feudal Georgia (V-X cc). In curative activity were involved: Georgian monastery temples, Georgian Lavra Sabatsminda, Shio Mghvime, Khanzhtis Savane, Vardzia and Vanistavi Monastries. With curative and medical literature were engaged noted figures: Martviri Sabatsmindeli (VII c), Ioane Zedazneli, Abibo Nekreseli, Shio Mghvimeli (VI c), Ilarion Khartveli (IX c), Grigol and Epifane Khandztels (VIII- IX cc) etc. In Georgian history of Medicine a special place belongs to theclassic era (XI-XIII c), in this period in Gelati and Ikhalto Academies were created remarkable works of arts of scientific and practical medicine and pharmacy:,,ustsoro Karabadini of Kananeli,,,Tsigni Saakimoi of Khojakopili. One can found there a lot ofinformation about anatomy and physiology, hygiene, therapy and medicinal remedies; several drug forms were widely represented, the accuracy of this information is amazing and many things are the subject of future research. There were a Hospital and Tsamaltkhana At the Gelati Monastry, the medicine was taught at the Academy, teachers were Ioane Petritsi and Arsen Ikaltoeli. In,,Vepkhistkaosani ("Knight in the Tiger's Skin") in the genial poem of Shota Rustaveli there are 34

35 expressions,clarifying author s knowledge in medicine (M. Shengelia). SinceX century Georgians are engagedin curative and pharmaceutical activities in Athon s Iver Monastry in Greece. Revival of Georgian medical sciences and pharmacy had been in progress until Mongolian invasion. Mongolian invasion (XII c.) disintegrated unity of the Georgian State. Country s cultural-educational centers were demolished. Despite of the hard economical situation, since the beginning of XVI century advanced part of the Georgian society managed to restore medicine and pharmacy. The most importantmedical arts ofgeorgian renaissance represent,,karabadini by Zaza Panaskerteli and Davit Batonishvili s "Iadigar Daudi". Listed books are unique worksforhistory of Georgian medicine and Pharmacy. In XVII-XVIII centuries catholic missionaries have promoted a revival of Georgian Pharmacy, opening In 1740 in Tbilisi a Pharmacy - so called,,tsamalt-khana. The lack of national medical personnel caused a necessity of inviting foreign specialists, particularly from Europe.King Erekle II paid a special attention to the Pharmacy, in his time a medical school was opened. Permanent invasions from the side of occupants have ruined the Georgian State. Sciences, and among them medicine and pharmacy were degraded. In 1806 the first state pharmacy was openedin Tbilisi, a special garden for medicinal plants domestication was arranged. Special laboratory was open close to the pharmacy in order to produce the drugs from the endemic plants. The firstmedical institution with clinic and pharmacy in 1808 was opened in Tbilisi in 1808.In1829 a pharmacy with free sell right for medicines was opened by Sherberg. In 1853 the second pharmacy was opened in Tbilisi. In 60ies of XIX century a number pharmacies were founded in different cities of Georgia. In pharmacies, in and in pharmacies were functioning in Georgia. Meanwhile medicinal remedies were mainly imported. In 1921 the Health Public Commissariat was founded, which conducted a nationalization of pharmacies and created its own pharmaceutical branch. In 1924 sakhmedvachroba public medicines trade was organized for providing medicinal remedies. In 1921 a Pharmaceutical division was openedat the Medical faculty of the Tbilisi State University. And in 1937 Tbilisi State Pharmaceutical Institute was formed, with profiled departments of: pharmaceutical chemistry, drug technology, pharmacognosy, pharmaceutical organization. The director of Institute was professor Iovel Kutateladze, deputy director was prof. Pavle Chumburidze. CurrentlyFaculty of Pharmacy is one of the facultiesin Tbilisi State Medical University. This faculty has solved a problem of high education pharmaceutical personnel straining in Georgia. Many generations of scientific and practical personnel havebeen brought up. In Georgian pharmaceutical education, personnel training and science development process have contributed our noted pedagogues: academician Iovel Kutateladze, professors: Nikoloz Maskhulia, Pavle Chumburidze, Valerian Shotadze, and Aristach Mshvidobadze.Thank to their and their students fruitful work Georgian pharmacy branch comprises more than one hundred doctors of sciences, professors, several thousand of pharmacists. In 1994a pharmaceutical divisionswere founded atkutaisi Akaki Tsereteli State University, and later in 2009 in Batumi Shota Rustaveli State University. In 1932 Pharmacochemistry Institute of Academy was founded, which bears the name of its founder Iovel Kutateladze. The Institute was carrying and is continuing a fruitful scientific-research activity towards the revealing and study of Georgian medicinal plants. Initiators and organizers of forming this scientific centre were academician Iovel Kutateladze and prof. Aristach Mshvidobadze. Iovel Kutateladze, Nikoloz Maskhulia, Pavle Chumburidze, Valerian Shotadze, Aristach Mshvidobadze, Ketevan Mujiri and their co-workers as early as the beginning of the Great Patriotic Warhave investigated and implemented in industry novel medicinal remedies: Digalen-Neo, Periplocin, Filicol, Satituran, Sukradbel, Tealbin, Elargol and others. Experimental and clinical trials of these 35

36 preparations have performed by the noted Georgian doctors: Dimitri Gedevanishvili, Grigol Gvishiani, Aleksandre Aladashvili, Mikheil Tsinamdzghvrishvili, Nikoloz Khipshidze. During the II World War in laboratories of Institute a pack of medicineswere prepared and delivered to Caucasian front. In in Patriotic war were called-up graduates and postgraduates of the Pharmaceutical Institute. Georgian pharmacists honorably have performed duties for homeland. Contribution and achievements of many of them by orders and medals were denoted. In 60ies a lot of teachingscientific literature have been issued and by the professors and pedagogues of Faculty of Pharmacy of the Medical Institute:,,Analytical chemistry and,,pharmaceutical terminology by Iovel Kutateladze, monographs and collections of methods of biochemical analysis by Vladimer Asatiani,,,Pharmaceutical chemistry textbook of Aristach Mshidobadze,,,Pharmacognosy of Valerian Shotadze,,,Physical-chemical methods of drug analysis and,,ion-exchanger polymers research by Bidzina Chumburidze, monographs of Lina Eristavi, Grigol Chixladze, Kote Sandomisashvili etc. In 70-ies the symposium materials -,,Chromatographic methods in Pharmacy,,,Materials of the first Pharmacists congress, collections of scientific works etc. were issued.during last years hundreds of scientific works have been published, some of them abroad. Since 60-ies the advanced representatives of the pharmaceutical society took part in international scientific forums in European countries. As an embryo of pharmaceutical manufacture in Georgia should be considered a galenic-packing laboratory at the central warehouse of the pharmacy administration, which was organized in In 1930 on the basis of this laboratory construction of pharmaceutical factory was started. In 1936 mentioned pharmaceutical factory was transmitted to the industrial union Pharmkhimmretsvi. In 1937 in Georgia Batumi caffeine factory was lunched. And from 1942 factory of organic therapeutic preparations was operated. Since 30-ies of XX century in Tbilisi is functioning a scientific-research institute of vaccines and serums and proper enterprise. Apart of the abovementioned enterprises, in Georgia there weremedicinal plant farms of Kobuleti and Shuakhorgi, which at that time were supplying pharmaceutical enterprises. After formation of Georgia as an independent state, a pharmaceutical industry rapidly was developed. Nowadays leading pharmaceutical industries are: GMP, Aversi-racionali, Neopharm, Tbilkhimpharm, etc. Georgian pharmaceutical enterprises are producing more than 500 pharmaceutical preparations serially. Currently in Georgian pharmaceutical industry s development significantly are contributing: professor Aliosha Bakuridze, Giorgi Antadze and Gogita Datukishvili. In 1951 Georgian Association of Pharmacists was founded, as a president of which an academician Iovel Kutateladze, as a deputy president prof. Aristach Mshvidobadze and as a scientific secretary Grigol Chikhladze were elected.after a month pharmaceutical association of Tbilisi was established. During the 1952 pharmaceutical associations were founded in Kutaisi, Sokhumi, Batumi and Gurjaani. In associations were established in Ozurgeti, Gori, Telavi, Rustavi and Zugdidi. The project of regulations of the Georgian society of pharmacists was composed by prof. Aristach Mshvidobadze and prof. Bidzina Chumburidze. Regulation of the pharmaceutical society primarily aimed at the improve of pharmaceutical personnel qualifications and skills; support of pharmaceutical establishments' material-technical basis; providing population with medicinal remedies; improvetheculture of pharmaceutical service; protection of the rights of community members; raise the level of scientific work; improve a quality of medicines; extension of pharmaceutical industry and scientific pharmacy development. Since 60-ies has intensified ties with European countries, it became possible to participate in European countries and in international scientific conferences and congresses.business contacts with foreign scientists have contributed to the development of pharmaceutical science and practice. 36

37 In 70-ies has further expanded contacts with foreign scientists and scientific institutions. scientific missions for experience exchange and modern technologies elaboration came in practice. Here are those measures in which pharmaceutical society played a great role. Over the second half of the seventies and in 80-ies the organization of all-union and international conferences has started in Tbilisi. Every year around this period several dozen of youths defended thesis (dissertation). Scientific works werepublished, textbooks, monographs, abstract books were issued. Science has become a priority, scientists were respected and that s whythere was great desire for science. Respect towards the ancestors and traditions was honored. Exceptionally were celebrated anniversaries, memory events of scientists and meritorious figures, ancestors contribution and commitment to the homeland were appreciated. A broad practice of arranging scientific sessions on the urban and rural areas has left a deep mark in pharmaceutical society of Georgia. Every year from 1954 to 1980 disposal scientific sessions were arranged. On these sessions reports were presented by scientific stuffs, as well by Heads of pharmacy departments and pharmacy stuffs. These sessions were real demonstration of professional potential. In these events actively were involved: Iovel Kutateladze, Aristach Mshvidobadze, Petre Gelbachiani, Bidzina Chumburidze, Lina Eristavi, Eter Kemertelidze, Ketevan Mujiri, Levan Chkhatarashvili, Viktor Bostoghanashvili, Guram Tsagareishvili, Valentina Vachnadze, Otar Nishnianidze, Kote Sandomisashvili, Mikheil Chichinadze, Varden Sephiashvili, Grigol Chikhladze, Roman Makharadze, Vajha Eriashvili, Simon Ujmajuridze, Viktor Dgebuadze, Aliosha Bakuridze, Nodar Zabachidze, Davit Chincharadze, Rezo Skhiladze etc. In 1970 in Tbilisi was held a scientific conference on the medicinal plants. In 1977 a symposium -,,Chromatographic methods in Pharmacy was heldin Tbilisi, in symposium were taking parts noted chromatographists from foreign countries. Symposium materials were issued. In connection with this event Academy of Sciences of USSR awarded Bidzina Chumburidze with honorary certificate for,,chromatography development for the benefit of mankind. In 1978 in Tbilisi Georgian pharmacists I congress was held. The convention was attended by the delegates from all Republic. Congress materials were published. In 1982 All-Union scientific conference on pharmacokinetics was held in Tbilisi. Issuing the textbooks, monographs and books as achievement of scientific pharmaceutical society s activity should be considered. In this regard there should be noted publications of Iovel Kutateladze, Vladimer Asatiani, Aristach Mshvidobadze, Petre Gelbachiani, Bidzina Chumburidze, Roman Macharadze, Vajha Eriashvili, Aliosha Bakuridze, Lina Eristavi, Ether Kemertelidze, Guram Tsagareishvili, Nodar Zabachidze, Vladimer Makharadze etc. Since 90 th of last century pharmaceutical society got an additional concern the drafting of laws and regulations of pharmaceutical field. Mentioned regulations were drafted, discussed and approved by the Parliament. Inthe later years their continuous changes have started. This process is still in progress. Currently in Georgia a reform in pharmaceutical personals training and professional skill processis underway. In Pharmacy a three-level educational system was established. This system includes: undergraduate, graduate and postgraduate studies. In the second half of XX century Georgian Scientific-pharmaceutical Association has played an important role in the development of scientific and practical pharmacy., This is particularly reflected in the preparation of stuff and their professional skills; in establishment links between the World Health Organization and International pharmaceutical societies. All this made consolidation of our society domestically and as well established connections internationally. This period was bearer of a special charge. Currently Georgian pharmacy is facing several problems, it is necessary to: - Set up and enforce to ensure the State system for medicines quality assurance; - Restore and legalize the Pharmacy as a Regulated Profession; - Set up the prescription institute; 37

38 - Regulate the pharmaceutical service state system; - Regulate drug pricing according to the European countries; - Restore and set up an antimonopoly law; - Establish an arbitration Drug Quality Control Laboratory; - Set up drug monitoring service. Drug registration in Georgia must ensure its quality, efficiency and safety. Relations with international organizations of Pharmacists and pharmaceutical societies of foreign countries since 1960 have been resumed. Participation in congress of Czech pharmacists in 1961 was a new era in Georgian pharmacists life;as well in Leipzig, German pharmacists congress in 1962; Mission to Budapest for experience exchange in 1962; to Japan in 1966; participation in congress of Yugoslavian pharmacists and etc. In Italy in in US in in India in in Greece in in Austria in Georgian delegation on 60 th congress of pharmacists was solid: prof. Amiran Gamkrelidze, prof. Bidzina Chumburidze, prof. Roman Makharadze, prof. T. Chumburidze, prof. A. Tomadze, M. Giorgobiani etc. In France (Nice) the Georgian delegation consisted of three person: prof. Bidzina Chumburidze, prof. Tamaz Chumburidze and DaviT Kiladze. In 60ies and 80-ies in scientific forums of European countries pharmaceutical societies were taking parts Lina Eristavi and Bidzina Chumburidze. In 90ies relations were established with the World Health Organization and its European regional organization.seminars, meetings, business trips were organized for the purpose of sharing experience. Such events were held in European cities: Kopenhagen, Budapest, Berlin, Milan, Prague, London, Geneva, Vienna, Warsaw etc. International congress with the motto:,,health and Medicine five times was held in Tbilisi. Organizational committee members were: Roman Makharadze and Aliosha Bakuridze. In 2002 in Tbilisi international congress of pharmacists took place. At this congress several reports were presented by the members of Tbilisi pharmacists organization: Eter Kemertelidze, Bidzina Chumburidze, Aliosha Bakuridze, Tamaz Chumburidze and A. Tomadze. Since1980 to till today we have a business relationship with the European Pharmacopeia Committee. Bidzina Chumburidze is an expert of the European Pharmacopeia Committee. In 2008 Tamaz Chumburidze was elected as a member of the Europharmforum Assembly of the World Health Organization. Noteworthy thatgraduate of Pharmaceutical faculty of the Medical University Nana Menabde is a Deputy Director of the World Health Organization's European region.president of the Pharmacists Association is the Rector of Batumi University professor Aliosha Bakuridze. A scientific-creative relationship we have with the Universities of Marcel, Mediterranean, Liege, Ljubljana, Bolus, Kharkov etc. In the beginning of 90ies of the last century in agenda came a state reform in pharmacy. By the Ministers Council resolution, in 1991 was formed a,,certification Committee of medicinal remedies, food products and new technologies, " which in 1994 was transformed into a pharmacology committee, the pharmacy administration was reorganized; Pharmaceutical establishments were privatized; Pharmacological and pharmacopeial committees were formed; Were created the Department of Drug and Pharmaceutical activity;an inspection for controlling pharmaceutical activity; Drug Quality Control State Laboratory. Pharmaceutical activity s regulatory agencies autonomous republics and regions. Currently these structures are united in medical activity's regulating department of the Ministry of Health. Department of Pharmacy doesn t exist. The reform was focused on the pharmaceutical enterprises and farms of industrial raw material, they were privatized. Postgraduate certification system of medical and pharmaceutical stuff was set up, pharmaceutical establishments' licensing offices were formed. The Presidium of Georgian Association of Pharmacists together with the leaders of the Ministry of Health and Committee of Health and Social Care of the Georgian Parliament have prepared the laws on the:,,drug and pharmaceutical activity,,,medical personnel s continuous preparation,,, Special control's subjected medications flow on,,,licensing the medical and pharmaceutical establishments. 38

39 In addition to the above-mentioned laws, a valuable work was carried on the rules and regulations of pharmacists certification. Colossal work was undertaken and successfully accomplished by the professors of profiled departments of faculty of Pharmacy of the Tbilisi State Medical University. It comes to composing, reviewing, approving and publishing of the test-questionnaire for certification exams. The laws governing the pharmaceutical activity needs the relevant bylaws. Up to 52 bylaws have been composed, reviewed, approved and published. DEPARTMENTS OF PHARMACEUTICAL FACULTY OF THE TBILISI STATE MEDICAL UNIVERSITY DEPARTMENT OF PHARMACEUTICAL AND TOXICOLOGICAL CHEMISTRY Department of Pharmaceutical chemistry was formed in 1921 in Tbilisi State University. Until 1931 the department was managed by professor Iovel Kutateladze. In the first years at the department there were working Nikoloz Maskhulia and Pavle Chumburidze. From 1931 till 1942 the governance was relayed to professor Nikoloz Maskhulia. From 1942 till 1973 the head of department was professor Aristach Mshvidobadze. From 1973 till 1996 the department was managed by the academician of medical-biological and medical-social sciences professor Bidzina Chumburidze. From 1996 the department of pharmaceutical and toxicological chemistry is leading the academician of medical science of academy professor Roman Makharadze. The courses in pharmaceutical and toxicological (forensic) chemistry were delivered by the following professors and lecturers at different times: Aristach Mshvidobadze, Nino Jhgenti, Irina Enukidze, Olia Sarjveladze, Pavle Chumburidze, Luba Esebua, Ketevan Mujiri, Nunu Iobashvili, Klara Gamsakhurdia, Shota Ghlonti, Irakli Natroshvili, Simon Ujmajuridze, Nazi Surmava, Ketevan Baramidze, Maia Kurcikidze etc. Currently at the Department of Pharmaceutical and Toxicological Chemistry there are: Bidzina Chumburidze, Roman Makharadze, Lia Adeishvili, Tamaz Murtazashvili, Madona Jorjikia, Luiza Kunchulia, Naili Shengelidze, Tamar Chikviladze, Nino Imnadze, Hilda Ioramashvili, Tamar Otarashvili, Nino Nijharadze and Nana Lekishvili. Presently at the department in teaching activities are engaged: Bidzina Chumburidze, Roman Makharadze, Lia Adeishvili, Tamaz Murtazashvili, Madona Jorjikia, Luiza Kunchulia, Naili Shengelidze, Tamar Chikviladze, Nino Imnadze, Hilda Ioramashvili, Tamar Otarashvili, Nino Nijharadze, Nana Lekishviliand Tamar Muzashvili At the departmenta Master Program is on,which is managed by professor Bidzina Chumburidze. Department is actively involved in preparation and edition of teaching textbooks. In this regard especially noteworthy editions of Aristach Mshvidobadze, Bidzina Chumburidze, Roman Makharadze, Lia Adeishvili etc. For the edition of textbook in Pharmaceutical chemistry Bidzina Chumburidze was awarded the state prize in the field of science and technology. Department stuffs were and are engaged in significant scientific-research activity. More than 30 dissertations have been prepared and defended, over the 25 patents have been obtained. Hundreds of scientific works, several monographs, conference materials, abstract books etc have been published. Several scientific school-directions have been formed and valid: - Drug standardization; - Chromatographic methods for drug analysis; - Narcological-toxicological analysis; - Pharmakinetik study. Department actively takes part in the drafting of pharmaceutical law projects. The problem lies with the renovation of department s material-technical base, equipping laboratories with modern equipments. 39

40 DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY Department of Pharmaceutical technology was established in 1935 as the,,cathedra of Drug and Galenic Technology. In 1967 it was renamed as the,,cathedra of Drug Technology, and in 2004,it was renamed again into the,,cathedra of Pharmaceutical Technology. From the academic year of 2006/2007, the cathedra was eventually called as the Department of Pharmaceutical Technology. The cathedra was governed by: Irakli Burjanadze in ; Prof. Petre Gelbakhiani in ; Docent Levan Chkhatarashvili in , Docent Ipolite Moniava in ; Since 2000 and till now the cathedra has been managed by Prof. Aliosha Bakuridze. The professors listed below were engaged at the cathedra at different times: Pavle Chumburidze, Petre Gelbakhiani, Aristrarkh Mshvidobadze; Docents: Irakli Burjanadze, Samson Asatiani, Levan Chkhatarashvili, Revaz Skhiladze, Nargiza Sartania, Tina Dolaberidze, Mariam Trapaidze, Grigol Chikhladze, Jemal Enukidze, Leila Kereselidze, Nazi Ghudushauri; lecturers: V. Villareti, Tamar Bezhanishvili, Revaz Murghulia, Guram Tsotsoria. The following subjects are delivered at the department: Technology of galenic agents, Technology of ready drug forms, Biopharmacy, Biotechnology, Technology of cosmetics and perfumery, Technology of homeopathic and veterinary agents and Processes and devices in pharmaceutical industry. Currently at the department in teaching activities are engaged: Aliosha Bakuridze, Ipolite Moniava, Gulnara Mikaia, Jemal Phutkaradze, Ia Tsurtsumia, Nino Kurdiani, Nino Tsagareishviliand Lasha Bakuridze. The main scientific direction at the Department of Pharmaceutical Technology refer to the development of resource-reserving technologies for treating the raw material and preparation of modern drug forms on the base of the latter. Hundreds of scientific papers, monographs, textbooks are edited and over the 50 patents are obtained. 2 Doctoral and 17 Candidate dissertations have been implemented and granted at the cathedra since Doctoral programs are on at the department for now. DEPARTMENT OF SOCIAL AND CLINICAL PHARMACY Organization and History of Pharmaceutical Activity had been taught since 1926 at the Cathedra of Pharmacy and Pharmacognosy, pertaining to the Faculty of Medicine at Tbilisi State University (the Head Mcs in Pharmacy Eduard Aboli). In Cathedra was governed by professor Petre Gelbachiani and from 1972 to 1990 by docent L. Chkhatarashvili. In 1990 the Cathedra of Drug Technology was divided into two parts, to form the Cathedra of Pharmaceutical Activity Organization and Economics, and Docent Levan Chkhatarashvili was assigned as the head till In the cathedra was headed by professor Guram Tsagareishvili. Since 1997 and till now it has been headed by the academician of medical-social science Academy, Prof. Vazha Eriashvili. In 2001the cathedra was renamed in the Cathedra of Social and Clinical Pharmacy, and in 2006, it was renamed again and called as the Department of Social and Clinical Pharmacy. At the Department there were working: G. Chichladze, P. Geleishvili, R. Skhiladze, B. Bochorishvili, J. Enukidze, I. Murghulia etc. The following subjects are delivered at the department: Organization of Pharmaceutical Activity, Economy and History, Clinical Pharmacy, Management and Marketing, Commodity Research, Pharmaceutical Business Basics, Information and Computer Technologies. Since 2008 the Master program,,pharmaceutical Management is on and PhD students are prepared. The main scientific directions of the department are: Pharmaco-economical study and marketing of drugs and medical agents, Management of pharmaceutical activity,,,biblical principles of pharmacology etc. The current academic staff at the department are: Vazha Eriashvili an honorable academician of the Academy of intercontitental medical-social sciences, Full Professor; Tamaz Chumburidze Associated Professor, Academic Doctor in Pharmacy; Assitant Professors: Nino Nemsitsveridze, Tea Zarkua, Natia Kvizhinadze. The invited 40

41 Academic Doctors are: Nana Gorgaslidze, Neli Nikuradze and Nana Dughashvili, Pedagogues: Sh. Grdzelishvili, S. Tomadze, N. Iamanidze, N. Bachtadze, E. Phruidze. In by the stuffs 8 textbooks have been issued: 1. Social Pharmacy (Author and Editor V. Eriashvili, co-auths: N. Gorgaslidze, Sh. Grdzelishvili, T. Zarkua, I. Murghulia, N. Nikuradze, G. Papashvili). 2. Dictionary of Pharmaceutical Market Economy (Auth.: N. Gorgaslidze) 3. Basics of Pharmaceutical Business (Auths.: V. Eriashvili, N. Dughashvii) 4. Clinical Pharmacy (Auths.: T. Chumburidze, T. Kikalishvili) 5. Medical and Pharmaceutical Commodity Research (Auth.: Sh. Grdzelishvili) 6. Management of Pharmaceutical Activity (Auth.: N. Nemsitsveridze) 7. Basics of Pharmaceutical Marketing (Auths.: T. Zarkua, V. Eriashvili) 8. Drug Standardization and Quality Management (Auths.: B. Chumburidze, T. Chumburidze, T. Chikviladze). DEPARTMENT OF PHARMACOGNOSY AND BOTANY Department of Pharmacognosy and Botany was established in 1921 at pharmaceutical division of Tbilisi State University. The first chief of the cathedra was Academician I. Kutateladze ( ). From 1926 the Cathedra of Pharmacognosy became an independent unit, which, as the subordinate of Pharmaceutical and Medical Institute, was managed by Prof. E. Aboll ( ), Prof. V. Shotadze ( ) and Prof. L. Eristavi ( ). Since 1997 the cathedra has been headed by Prof. J. Kuchukhidze. Since 1930, the course of botany has added to the Cathedra of Pharmacognosy, which, after organization of Pharmaceutical Institute, was rearranged into the Cathedra of Botany, and from 1953 was joined to the Cathedra of Pharmacognosy. The known scientists and lecturers were performing at the Cathedra of Pharmacognosy at different times, which were: Master of Pharmacy, K. Bakhtadze, Prof. Z. Kanchaveli, Academician D. Sosnovsky, Prof. T. Kezeli, Docent B. Bakradze, Docent T. Kachukhashvili, Docent D. Kavkasidze-Virsaladze, chief lecturer N. Gavasheli, Docent L. Kvitaishvili, Murman Nijharadze, Head teacher Nadia Gavasheli, Assistant professor Maia Kurcikidze etc. Current academic staff at the department involves: - Jumber Kuchukhidze Professor; - David Chincharadze Professor; - Dali Berashvili Associated Professor; - Malkhaz Jokhadze Associated Professor; - Lasha Mskhiladze Assistant-Professor; - Anna Bozhadze Assistant-Professor. Invited pedagogues at the department are: Manana Maisashvili, Lali Zardiashvili. Scientific works are led simultaneously with the study process at the department. The chief direction of scientific activity was and still remain to be the search of herbal treasures in Georgian flora for creation of new medical agents. The scientific grant projects presented by the department were funded in 2008 and 2009 by the National Scientific Fund of Georgia, which were:,,cultivation of rare plants and those under danger of extinction, belonging to the family of..., retrieving and standardization of medical agents from these species Scientific Manager of the project, Associated Professor M. Jokhadze. Polyphenols derived from the Populus family met in Georgia, as the potential source of antioxidant and cytotoxic drugs Scientific manager of the project, Professor J. Kuchukhidze. In 2006 a textbook in Pharmacognosy of Lina Eristavi, and in 2012 a textbook in Botany for Pharmacy students by Jumber Kuchukhidze and Malkhaz Jokhadze have been issued. 41

42 ALLELOPATHY IN THE SEARCH NEW DRUGS 1 Francisco A. Macías, 2 Mariola Macías, 1 Elena Arroyo, 1 Alejandro Santana, 1 Gara R. Barbero, 3 Juan M. Sanchez-Calvo, 1 Guillermo A. Guerrero-Vasquez, 1 José L. G. Galindo, 1 Nuria Chinchilla 1 Grupo de Alelopatía, Departamento de Química Orgánica, Instituto de Biomoléculas (INBIO), Facultad de Ciencias, Universidad de Cádiz, C/ República Saharaui, s/n, Puerto Real (Cádiz) Spain; 2 Departamento de Anatomía Patológica, Biología Celular, Histología, Historia de la Ciencia, Medicina Legal y Forense y Toxicología, Facultad de Medicina, Plaza Fragela, 9, 11003, Cádiz, Spain; 3 Departamento de Biomedicina, Biotecnología y Salud Pública Unidad de Investigación del Hospital Universitario Puerta del Mar, Avda. Ana de Viya, Cádiz Spain Plants have their own communication and defence mechanisms and allelochemicals are, in fact, natural herbicides, bactericides, fungicides, within others. Allelopathic studies develop new compounds that may lead to obtain new drugs since they offer new modes of action and more specific interactions. Following the economy of resources principle one defence metabolite is cheaper in terms of resource investment (energy, NADPH, carbon) if it can defend the plant from more than one organism. Here, we illustrate this principle with several examples where allelochemicals, in addition to phytotoxic activities, have shown other interesting biological properties. Thus, epoxycurcuphenols from Helianthus annuus, that were identified as precursors of heliannuols, (a family of allelochemicals isolated from sunflower), showed potential use as immunosuppressants. Similarly, a secoguaianolide isolated from Artemisia gorgonum showed high activity on the wheat coleoptile bioassay, as well as on STS phytotoxicity bioassay. Additionally, this compound was tested on human cell culture showing apoptosis induction on ovarian cancer cells. In the course of our research toward the synthesis of heliannuol D we obtained two aromatic diasteroisomers, heliannosides that present an oxirane group. They showed interesting biological activities when evaluated in animal and plant cells. Expoxycurcuphenols were evaluated for their effects on cytokine production by human primary CD4+ T cells and on cell division on the human tumoral cell line Jurkat, murine antigen specific CD4+ T cell line D5, murine Primary CD4 T Cells from TcR Transgenic DO11.10 mice, human primary naïve PBMC and human primary CD4+ T cells. In the case of the lymphoid human cell line Jurkat, addition of sesquiterpenes at a final concentration of 1μM impaired cell division in almost 100% of cells. For the evaluation on plant cells the wheat etiolated coleoptiles has been used. In order to gain a deeper understanding of the structural requirements for bioactivity in this family of compounds, heliannosides, we carried out a Structure-Activity Relationship (SAR) study and synthesized 24 derivatives with different side chains and substitution patterns in the aromatic ring and the alkylic side chain. The compounds were classified into three families depending on the length of the side chain and the substitution pattern at the oxirane ring: heliannosides C6 (oxirane ring with two methyl groups in the last carbon, and a side chain that is six carbons in length), heliannosides C5 (with a side chain five carbons long and the oxirane ring without any terminal methyl groups) and heliannosides C4 (with a four-carbon side chain and an oxirane ring without any methyl group). All compounds were obtained as a pair of diastereoisomeric products. Other examples are quinones. Naphthotectone has been proposed as one of the responsible of the allelopathic activity of teak. Preliminary assays have shown that this compound presents citotoxic activity, using HeLa cells, as well. They are privileged structures in medicinal chemistry due to their characteristics, structural properties and biological activities on prokaryotic and eukaryotic. 1,4-naphthoquinones exhibit strong action as antimalarial, antibacterial, antifungal, and anticancer agents. A Structure-activity relationship study (SAR) of 52 naphthoquinone analogues looking for new natural product based drugs has been performed. 52 compounds were prepared and evaluated for its antimicrobial and antifungal activity on Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Enterococcus faecalis ATCC 29212, Staphylococcus aureus, Candida krusei ATTC 6258, Candida parapsilosis ATCC and Cryptococcus neoformans using broth microdilution method. 42

43 MAKING BETTER USE OF DATA IN DRUG DESIGN Johann Gasteiger Computer-Chemie-Centrum and Institute of Organic Chemistry. University Erlangen-Nuremberg The development of a new drug is an expensive and time-consuming process. Reasons are the complex nature of the relationships between chemical structure and biological activity and the huge amount of data to be considered. Furthermore, many additional properties such as adsorption, distribution, metabolism, excretion and toxicity (ADME-Tox) of a compound have to be considered and optimized during the process of developing a new drug. The relationships between the structure of a molecule and its biological activity are too complex to be calculated directly by theoretical methods. In such a situation, one has to try to learn from the data accumulated for a series of compounds. These data on compounds and their associated structures have to be used to generate a model that allows the prediction of new data. A variety of mathematical methods for data analysis and data mining has become available to develop such a model for predicting biological activity and ADME-Tox properties. In this process, the representation of chemical structures is of critical importance. Depending on the amount of chemical compounds that have to be considered an appropriate structure representation has to be chosen. In lead discovery, where sometimes millions of chemical structures have to be handled, quite often only the constitution (2D structure) of a compound is considered. When more and more detailed information on a compound becomes available, the 3D structure of this compound or molecular surface properties such as the molecular electrostatic potential or hydrogen bonding potential can be taken into account. Thus, an entire hierarchy of representing chemical structures has been developed [1]: From the constitution through 3D structures to molecular surface properties. Furthermore, also chemical reactions have to be modeled and methods have been developed for the prediction of the outcome and products of chemical reactions and for the prediction of the metabolism of compounds [2]. Application of all these methods to the - identification of a protein target for a desired biological activity, - discovery of new lead structures, - separation of compounds into different biological activities, - optimization of lead structures to enhance biological activity, - prediction of other physical, chemical and biological properties such as ADME-Tox properties. have been developed and will be presented with examples. This includes the prediction of the solubility of organic compounds in water, of the distribution of a compound between water and lipid phase, of the crossing of a compound of the blood-brain barrier, of intestinal absorption and of the metabolites of a compound. Recent efforts in pharmaceutical industry concentrate on the prediction of a variety of toxicity endpoints of potential drug candidates. The European Union and the European Federation of Pharmaceutical Industries have partnered in the Innovative Medicine Initiative to fund projects where industry and academia collaborate to develop models for the prediction of different toxicity endpoints. To summarize: At the interface of chemistry, pharmacy and computer science a new field, chemoinformatics [3,4], has developed that can assist in the drug design process. Pharmaceutical industry has realized the importance of this field and has heavily invested into chemoinformatics, hiring experts in this field. In all major pharmaceutical companies, chemoinformatics has become, alongside bioinformatics, an integral part of the drug design process. As a consequence, chemoinformatics is being taught at a variety of universities in Europe, USA, Japan and China and the basics of chemoinformatics have been integrated into regular chemistry and pharmacy curricula. REFERANCES 1. J. Gasteiger, J. Med. Chem. 2006; 49: J. Gasteiger, J. Comput. Aided Mol. Design 2007; 21:

44 3. Chemoinformatics A Textbook, J. Gasteiger, T. Engel (Editors), Wiley-VCH: Weinheim; Handbook of Chemoinformatics, J. Gasteiger, Editor, 4 volumes, Wiley-VCH: Weinheim; 2003 BIOACTIVE NATURAL PRODUCTS FROM MARINE ORGANISMS Roussis V., Ioannou E. Department of Pharmacognosy and Chemistry of Natural Products, School of Pharmacy, University of Athens, Panepistimiopolis Zografou, Athens 15771, Greece The marine environment is a rich source of novel and unusual secondary metabolites, many of which have already shown considerable promise for development as therapeutic agents. Chemical studies on marine algae have led to the isolation of a large number of structurally unique secondary metabolites with a wide spectrum of biological activities. The biodiversity of the Mediterranean ecosystem hosts an immense number of indigenous species, as well as organisms that have migrated from the Atlantic Ocean, the Red and Black Seas. As part of our studies on the chemical composition and biological activity of marine organisms, our group has investigated a number of algal species found on the Greek coastline. Among the investigated species red algae of the genera Laurencia and Sphaerococcus have yielded a significant number of halogenated metabolites with cytotoxic and cytostatic activities. Brominated diterpenes from S. coronopifolius have exhibited settlement inhibition activity on the cyprids of Balanus amphitrite without toxic effects on non target organisms. The brown alga Dilophus spiralis was found to contain several new bicyclic and tricyclic diterpenes belonging to the classes of dolastanes and dolabellanes. Ulva rigida, a green cosmopolitan alga usually found in eutrophicated waters, is a rich producer of sulphated carbohydrates that have been incorporated in the production of nanofibers. Besides the isolation and structure elucidation of new natural products, investigations included pharmacological activity evaluations, geographic and seasonal variation studies and the development of in silico methodology for the prediction of biological activity. THE PLANT KINGDOM - A RICH SOURCE FOR POTENTIAL ANTI-INFLAMMATORY LEAD COMPOUNDS Stuppner H. University of Innsbruck, Institute of Pharmacy/Pharmacognosy, Center of Molecular Biosciences Innsbruck (CMBI), CCB, Innrain 80-82, 6020 Innsbruck, Austria Inflammation is part of numerous pathological conditions, including atherosclerosis, the metabolic syndrome, sepsis and cancer; all of them lacking satisfying treatment and/or effective concepts of prevention. Natural products have always been an important source of new drug leads. Almost half of the drugs currently in clinical use are of natural product origin and even today, in the post genomic era, plants, fungi, marine organisms, and microorganisms are still an important source for the development of new drugs [1]. 44

45 In the course of an ongoing Austrian research network project involving scientists from different countries we aim to identify and characterize natural products capable to combat inflammatory processes and disorders associated with inflammation. This is approached by a unique combination of strategies including i) pharmacophore modelling and virtual screening filtering experiments in order to identify compounds promising for pharmacological evaluation (molecular/computational approach) and ii) exploitation of traditional knowledge about plants to select promising candidates for phytochemical and subsequent pharmacological investigation (ethnopharmacology/bioguided approach). Candidates of both approaches are subjected to mechanistic studies as well as preclinical profiling. This lecture will cover some highlights of this interdisciplinary project. Acknowledgements. This work is financially supported by grant no S107 Drugs from Nature Targeting Inflammation from the Austrian Science Fund ( REFERENCES 1. Newman D.J., Cragg G.M. Natural Products As Sources of New Drugs over the 30 Years from 1981 to J Nat Prod. 2012; 75: PHYTOCHEMISTRY SEARCHING FOR A NEW ACTIVE NATURAL COMPOUNDS Oleszek W. Institute of Soil Science and Plant Cultivation, State Research Institute, ul. Czartoryskich 8, Pulawy, Poland Living plants produce a great number of chemicals that are crucial for their function and development. Some of these chemicals are primary metabolites, which include proteins (aminoacids), carbohydrates, fats, nucleic acids etc. However, besides these primary chemicals, the plants also produce so called secondary metabolites, which are specific to some taxonomic groups (families, genera). Their physiological function was questioned already in earlier work, but recent research has shown that they are important constituents of plants. They are formed under environmental pressure and play a crucial function in protecting plants against some environmental stresses. This group includes classes of compounds such as phenolics, carotenoids, alkaloids, saponins, glucosinolates, cyanogenic glycosides, terpenes etc. Each of these groups contains compounds with different biological activities, which in traditional medicine and ethno-pharmacology were used for centuries to cure or to protect from diseases. In Western Europe, the aging of population has been and currently is a driving force for the study of new phytochemical products, able to fight age-related conditions and prevent diseases such as high blood cholesterol level, high blood pressure, arthritis, obesity and cancer. In fact, only a few plants have been the subject of detailed investigations but more than 1000 species have been claimed to offer special benefits. However, in many cases no certainty exists about the real effects of dietary phytochemicals and more epidemiological surveys and clinical studies should be performed. Moreover, in various cases contrary effects are reported. Probably the main reason for this discrepancy is that many clinically tested products are, in fact, multicomponent mixtures since it is frequently very difficult to isolate only one component to study its biological effect. Present lecture focuses on a number of examples of secondary metabolite analysis, their chemical complexity, and challenges of their separation and structure elucidation. 45

46 TRADITIONAL ASIAN MEDICINAL PLANTS AS SOURCE OF ANTIOXIDANT AND ANTI-INFLAMMATORY COMPOUNDS Matkowski A., Ślusarczyk S., Nawrot I., Wożniak D. Department of Pharmaceutical Biology and Botany, Medical University of Wroclaw, Borowska 211, Wroclaw, Poland Medicinal plants are an essential part of traditional phytotherapy systems in many regions of Asia. Two famous and most widely used are Traditional Chinese Medicine and Ayurveda - ancient complex therapies considered today as the most complete complementary medicine systems. However, there are several other examples of such therapies that have been influencing each other through centuries of cultural, social, and political interactions. As a well-known example - Chinese Herbal Medicines included in Chinese Materia Medica listings cover more than 1500 plants and a great number (reaching ) of composite herbal preparations. Recently, several individual plants from eastern Asia have been added to European Pharmacopoeia and many more are on the waiting list. Some of the drugs have been known and valued in Western civilizations for centuries such as rhubarb and ginseng to name just the most recognized. A number of herbs and preparations are available in pharmacies, herbal stores and even more (and uncontrolled) over the Internet. Since the efficiency of traditional phytotherapies is based on the reinforcing of organism s natural healing power and the ability to restore energy homoeostasis, a likely mechanism of at least some of the activities is to interact with redox balance, and prevention of oxidative stress. Another aspect of internal homoeostasis pertains to the immune system as a major player in inflammatory response. Inflammation has been also studied as potential target of herbs that can restore the organism s physiological balance. During the past two/three decades, hundreds of crude herbs, extracts, and isolated compounds have been screened for their antioxidant and antiinflammatory properties in vitro and in vivo. In this context, several case studies will be presented from our research program on Asian medicinal plants acclimated in Central Europe. Specifically, we will show the results of in vitro antioxidant, proinflammatory enzyme inhibition, and phytochemical studies on - Salviae miltiorrhizae radix, Salviae przewalskii radix, Scutellariae baicalensis radix, representing TCM, and Perovskiae radix/perovskiae folium from traditional herbalism of Iran, Afghanistan and Pakistan. In conclusion, at least some of traditional medicinal plants of various Asian countries can be regarded as source of very efficient antioxidant and anti-inflammatory compounds, and this activity could explain some of their beneficial therapeutic and preventive usefulness. awaris regionsi gavrcelebuli lamiani sulfiduri talaxebis antebis sawinaarmdego moqmedeba da gamoyenebis usafrtxoeba n. gongaze, n. antelava, m. okujava, k. bakurize, q. pawkoria, m. RonRaZe Tbilisis saxelmwifo samedicino universiteti, samedicino farmakologiisa da farmakoterapiis departamenti, saqartvelo peloidoterapia mkurnalobis ert-erti uzvelesi metodia. miuxedavad samkurnalo sasualebebis mravalferovnebisa, Terapiuli miznit talaxebis gamoyeneba amjamadac ar kargavs mnisvnelobas. samkurnalo talaxebi, anu peloidebi, mdidaria sxvadasxva mineralebita da organuli nivtierebebit [2,3]. 46

47 samkurnalo talaxebs ganasxvaveben struqturisa da Semadgenlobis mixedvit, rac amave dros mat biologiur aqtivobasac ganapirobebs. am tipis talaxebi fartod gamoiyeneba sayrden-mamozravebeli sistemis daavadebebis, revmatizmis, poliartritis da sxva antebiti daavadebebis samkurnalod. meoce saukunis samocdaatian wlebsi Catarebuli kvlevebis Tanaxmad peloidebs gaacniat gamoxatuli efeqti antebis eqsudaciur fazaze. es, ertis mxriv, kanisa da lorwovanis receptorebze zemoqmedebis gzit qsovilebsa da organoebsi mikrocirkulaciisa da metaboluri procesebis refleqsuri cvlilebit aixsneba, meores mxriv ki makroergebis deficitis xarjze antebiti ubnis energetikuli uzrunvelyofis Semcirebas ukavsirdeba [2,4,5]. arsanisnavia, rom yvela peloids ar gaacnia samkurnalo Tvisebebi, amitom mati axali wyaros armocenis SemTxvevaSi aucilebelia rogorc struqturisa da Semadgenlobis dadgena, aseve biologiuri aqtivobis Sefaseba. kvlevis mizans warmoadgenda awaris regionsi gavrcelebuli lamiani sulfiduri peloidebis WaxaTis, kvirikesa da besumis talaxebis antebis sawinaarmdego efeqtis Sefaseba da mati gamoyenebis usafrtxoebis dadgena. antebis sawinaarmdego efeqtis Seswavla xdeboda vistaris jisis, zrdasrul, mamr TeTr 20 virtagvaze. virtagvebi 4 jgufad iyo dayofili, TiToeul jgufsi xut-xuti virtagva. antebis gamowvevis miznit yvela cxovls marjvena ukana TaTSi subplantarulad Segvyavda karageninis 1%-iani xsnaris 0,1 ml [1]. antebiti reaqciis gamowvevis Semdeg pirvel jgufsi virtagvebs TaTze wasmul iqna WaxaTis talaxi, meore jgufsi kvirikes talaxi, mesame jgufsi besumis talaxi, xolo meotxe, sakontrolo jgufsi gamoviyenet glicerini. talaxis datanidan 3 saatis Semdeg virtagvebis TaTebi suftavdeboda da onkometrulad fasdeboda TaTebis moculoba rogorc sakontrolo, aseve eqsperimentul jgufebsi. sakontrolo virtagvebisa da sakvlevi talaxebit namkurnalebi virtagvebis TaTebis moculobis Sedarebam gamoavlina, rom yvela sakvlev jgufsi antebiti TaTis moculoba statistikurad sarwmunod Semcirda sakontrolo jguftan SedarebiT. Walaxis talaxis zemoqmedebit TaTis moculoba sasualod 15.8%-iT (p<0,05) ufro mcire iyo, kvirikes talaxis zemoqmedebit 10.5%-iT (p<0,05), xolo besumis talaxis efeqti yvelaze metad iyo gamoxatuli da sxvaoba 31.6% (p<0,01) Seadgenda. mirebuli Sedegebis analizis safuzvelze SeiZleba davaskvnat, rom samive sakvlevi talaxis ertjerad gamoyenebas mohyveba antebiti TaTis moculobis sarwmuno Semcireba, rac miutitebs am lamiani sulfiduri peloidebis zemoqmedebit antebis eqsudaciuri fazis Semcirebaze. samedicino da kosmetologiur praqtikasi peloidebis gamoyenebis rekomendaciisatvis, biologiuri efeqturobastan ertad, aucilebelia mati usafrtxoebis gansazrvrac. Cvens mier Seswavlili iyo talaxebis zogadtoqsikuri moqmedeba, kerzod ki mwvave da qvemwvave toqsikuroba, kumulaciuri moqmedeba, agretve adgilobrivad gamarizianebeli da maalergizebeli efeqtebi. mwvave toqsikurobas vswavlobdit 50 araxazovan, zrdasrul, mamr TeTr Tagvze. Tagvebi davyavit 4 jgufad, matgan sami iyo eqsperimentuli (TiToeulSi 15 Tagvi), romlebsic gamoiyeneboda talaxebi, xolo meotxe sakontrolo (5 Tagvi) jgufi, romelsic talaxis nacvlad viyenebdit glicerins. TiToeuli eqsperimentuli jgufi davyavit kidev sam qvejgufad, romlebsic talaxs sxvadasxva dozit viyenebdit, kerzod pirvel qvejgufsi 1 g talaxi 20 g cxovelis sxeulis masaze, meore qvejgufsi 2 g / 20 47

48 g-ze, xolo mesame qvejgufsi ki 4 g/20 g-ze. mwvave toqsikurobis SeswavlisaTvis talaxis datana xdeboda ertjeradad. talaxis datanis Semdeg ori kviris ganmavlobasi Tagvebi imyofebodnen yoveldriuri dakvirvebis qves. dakvirvebis processi xdeboda integraluri macveneblebis - qceviti reaqciebis, nerv-kuntovani agznebadobis, refleqsebis, vegetaturi reaqciebis, garegnobis macveneblebis da letalobis registracia. macveneblebis registracia pirveli satis ganmavlobasi xdeboda at wutiani intervalit, ori saatis Semdeg, Semdgom ki ertxel dresi. Tagvebis masa ganisazrvra eqsperimentis dawyebamde da 14 dris Semdeg. ganxorcielebulma dakvirvebam acvena, rom yvela Seswavlili talaxis - WaxaTis talaxis kvirikes talaxis da besumis talaxis usualod datanis Semdeg, erti saatis ganmavlobasi, ori saatis intervalit da 24 saatis Semdeg integraluri macveneblebis normidan gadaxra ar arinisneboda. yvela cxoveli iyo janmrteli, aqtiuri, pirobiti refleqsebi da reaqcia gare garizianebaze normaluri, sakvebs irebdnen kargad. 14 dris ganmavlobasi Tagvebze yoveldriurma dakvirvebam normidan raime gadaxra ar gamoavlina. letaluri gamosavali ar dafiqsirebula. qvemwvave toqsikurobis Sefasebis miznit eqsperimentuli cxovelebi isetive jgufebad davyavit, rogorc mwvave toqsikurobis kvlevis SemTxvevaSi. sakvlevi talaxis datana Sesabamisi dozebit warmoebda ertxel dresi yoveldriurad 14 dris ganmavlobasi. am periodis ganmavlobasi Tagvebi imyofebodnen yoveldriuri dakvirvebis qves. sakvlevi talaxebis ToTxmeti dris ganamavlobasi gamoyenebam ar ganapiroba sakvlev cxovelebsi integraluri macveneblebis normidan gadaxra. kumulaciuri moqmedebis Sesafaseblad sakvlevi cxovelebis evtanaziis Semdeg ganxorcielda garegani datvaliereba da Sinagani organoebis (gulis, RviZlisa da Tirkmlebis) awonva. sakontrolo da sakvlevi jgufebis monacemebis Sedarebam ar acvena raime gansxvaveba. Catarebuli eqsperimentebis safuzvelze SeiZleba davaskvnat, rom sakvlev talaxebs rogorc ertjeradi, aseve ganmeorebiti gamoyenebisas, rezorbciuli moqmedeba ar gaacnia da Seswavlil dozebsi usafrtxoa garegani gamoyenebisatvis. qvemwvave toqsikurobastan ertad sakvlev cxovelebsi vafasebdit samive sakvlevi talaxis alergiis gamomwvev da gamarizianebel Tvisebebs. adgilobrivi gamarizianebeli da alergiis gamomwvevi efeqtebi kanze fasdeboda specialuri Skalis mixedvit: 0 TvalsaCino reaqcia ar aris 1 Ria vardisferi eritema mtel ubanze an mis periferiaze, 2 mkvetrad vardisferi eritema mtel ubanze an mis periferiaze, 3 witeli eritema mtel ubanze 4 kanis infiltracia da SeSupeba 5 eritema, gamoxatuli infiltracia, kerovani dawyluleba (nekrozi), SesaZloa hemoragiebis arseboba. sakvlevi talaxebis aplikaciidan 14 dris ganmavlobasi alergiuli reaqcia da adgilobrivi garizianeba ar AaRiniSneboda arc ert SemTxvevaSi. kanis reaqcia Sefasda 0 qulit. talaxebis datanis adgilze kani iyo gluvi, sufta, sisxxlcaqcevebi, gamonayari, dawyluleba da SeSupeba ar gamovlinda, kanis naowis gasqeleba ar arinisneboda. kanis Seferiloba da temperatura ar gansxvavdeboda garsemo qsovilebisa da sakontrolo cxovelebis analogiuri monacemebisagan. mirebuli Sedegebis safuzvelze davaskvenit, rom Walaxis, kvirikesa da besumis talaxebs adgilobrivi gamoyenebisas ar gaacnia alergiis gamomwvevi da gamarizianebeli moqmedeba. amrigad, Catarebulma kvlevam gamoavlina, rom awaris regionsi gavrcelebuli lamiani sulfiduri peloidebi xasiatdebian gamoxatuli antebis sawinaarmdego efeqtit da amave dros mat garegan gamoyenebas ar axasiatebs arc adgilobrivi da arc sistemuri 48

49 damazianebeli moqmedeba, rac miutitebs am talaxebis usafrtxoebaze da sasualebas izleva rekomendacia gavuwiot adgilobrivi garegani moxmarebisatvis samedicino da kosmetologiur praqtikasi. literatura 1. Департамент контроля качества, эффективности и безопасности лекарственных средств Министерство Здравоохранения Российской Федерации, Руководство по Экспериментальному изучению новых фармакологических веществ. М.: Холопов А.П., Шашель В.А., Перов Ю.М., Настенко В.П. Грязелечение. "ЭКО НЕДРА": Царфис П. Г., Киселев В. Б. Лечебные грязи и другие природные теплоносители. М.: Fioravanti A, Cantarini L, Guidelli GM, Galeazzi M. Mechanisms of action of spa therapies in rheumatic diseases: what scientific evidence is there? Rheumatol Int. 2011; 31(1): Zivná H, Maric L, Gradosová I, Svejkovská K, Hubená S, Zivný P. The effect of mud-bath therapy on bone status in rats during adjuvant subchronic arthritis. Acta Medica (Hradec Kralove) 2012;55(3): SUMMARY ANTI-INFLAMMATORY ACTION AND SAFETY OF SULPHIDE SILT PELOIDS DISTRIBUTED IN ADJARA REGION Gongadze N., Antelava N., Okujava M., Bakuridze K., Pachkoria K., Ghonghadze M. Tbilisi State Medical University, Department of Medical Pharmacology and Pharmacotherapy, Georgia Peloidotherapy is well known for a long time. Depending from mud structure and composition they can have broad variety of biological activities. The goal of our research was assessment of anti-inflamantory efficacy of Chakhaty mud, Kvirike mud and Beshumi mud - sulphide silt peloids distributed in Adjara region, and testing of their safety. The model of inflammation was developed using subplantar injection of 0,1ml 1% solution of Carageneen in right palm of the rat. Since 3 hours of application of different doses of muds we measured the volume of rat's palms using oncometric method and compared data of experimental and control groups. The comparison of fixed data revealed statistically reliable (p<0,05) reduction of palmar volume in all experimental groups, the most significant reduction was registered for Beshumi mud (p<0,01). Obtained results confirm anti-inflamantory activity of studded peloids and their effect on exudation phase of inflammation. After identification of peloid's efficacy we tested the safety of their external use in white mice. Namely, we studded acute and sub chronic toxicity, cumulative action, allergenic and irritating activity. The provided experiments established and confirmed that all muds under investigation are safe for external use and can be recommended for application in medical practice and cosmetology. reziume awaris regionsi gavrcelebuli lamiani sulfiduri talaxebis antebis sawinaarmdego moqmedeba da gamoyenebis usafrtxoeba n. gongaze, n. antelava, m. okujava, k. bakurize, q. pawkoria, m. RonRaZe Tbilisis saxelmwifo samedicino universiteti, samedicino farmakologiisa da farmakoterapiis departamenti, saqartvelo peloidoterapia mkurnalobis ert-erti uzvelesi metodia. talaxebis biologiuri aqtivoba damokidebulia mat struqturasa da Semadgenlobaze. kvlevis mizans warmoadgenda awaris regionsi gavrcelebuli lamiani sulfiduri peloidebis WaxaTis, kvirikesa da besumis talaxebis antebis sawinaarmdego efeqtis Sefaseba da mati gamoyenebis usafrtxoebis dadgena. virtagvebsi antebis modelis misarebad marjvena ukana TaTSi subplantarulad Segvyavda karageninis 1%-iani xsnaris 0,1ml. 49

50 talaxebis datanidan 3 saatis Semdeg virtagvebis TaTis moculobas vafasebdit onkometrulad. sakontrolo virtagvebisa da sakvlevi talaxebit namkurnalebi virtagvebis TaTebis moculobis Sedarebam gamoavlina, rom yvela sakvlev jgufsi antebiti TaTis moculoba statistikurad sarwmunod (p<0.05) Semcirda sakontrolo jguftan SedarebiT, efeqti gansakutrebit TvalsaCino iyo besumis talaxis gamoyenebisas (p<0.01). talaxebis biologiuri efeqturobis dadgenis Semdeg Cvens mier Seswavlili iyo talaxebis zogadtoqsikuri moqmedeba, kerzod ki mwvave da qvemwvave toqsikuroba, kumulaciuri moqmedeba, agretve adgilobrivad gamarizianebeli da maalergizebeli efeqtebi. Catarebulma kvlevam gamoavlina, rom awaris regionsi gavrcelebuli lamiani sulfiduri peloidebi ar xasiatdebian arc adgilobrivi da arc sistemuri damazianebeli moqmedebit, rac miutitebs am talaxebis usafrtxoebaze da sasualebas izleva rekomendacia gavuwiot garegani moxmarebisatvis samedicino da kosmetologiur praqtikasi. nasromi Sesrulebulia rustavelis erovnuli samecniero fondis mier dafinansebuli samecniero sagranto proeqtis # AR/269/8-403/11 farglebsi. STUDYING THE MECHANISM OF ACTION OF NEW ANTIPLASMODIAL HETEROCYCLIC HIT-COMPOUNDS VIA A SOLID SUPPORTED CHEMISTRY APPROACH 1 Rathelot P., 1 Kieffer C., 1 Verhaeghe P., 2 Hutter S., 3 Renault J., 1 Primas N., 1 Castera-Ducros C., 2 Laget M., 3 Uriac P., 4 Rault S., 2 Azas N., 1 Vanelle P. 1 Laboratoire de Pharmacochimie Radicalaire, Institut de Chimie Radicalaire, UMR CNRS 7273; 2 Infections Parasitaires, Transmission, Pharmacologie et Thérapeutique, UMR MD3, Aix-Marseille Université, Faculté de Pharmacie, 27 Boulevard Jean Moulin-CS 30064, Marseille cedex 05, France; 3 Institut des Sciences Chimiques de Rennes, UMR CNRS 6226, Faculté des Sciences Pharmaceutiques et Biologiques, 2 Avenue du Pr Léon Bernard, Rennes, France; 4 Centre d Etudes et de Recherche sur le Médicament de Normandie, UPRES EA 4258, FR CNRS 3038, UFR des Sciences Pharmaceutiques, Université de Caen Basse Normandie, Boulevard Becquerel, Caen Cedex, France We previously highlighted the antiplasmodial potential of various 2-trichloromethylquinazoline derivatives [1-6]. The hit compounds selected exert their antiplasmodial activity by a mechanism of action which is not shared by commercial antimalarial drugs. In order to elucidate this new original mechanism of action, we developped an affinity chromatography on immobilized inhibitors approach, from the hit presented above [7-8]. Such a project consists in the preparation of a specific matrix in which hit-compounds (inhibitors) are linked to a solid support via a linker located at an appropriate position onto the hit scaffold. The matrix is then put in contact with a plasmodium lysate which contains most of the parasite targets. Then, after washing the matrix, the hit-target complex can be identified by MALDI-TOF spectroscopy. 50

51 1) Mimotopes Lanterns: OH 1) Cl O 2) NH 2 -link-nh 2 3) Br HIT Cl O O H H N N link HIT 1) parasitic lysate with O O H H N N link TARGET HIT 2) Sepharose 4B beads: O C N link 1) H 2 N N H 2) H 2 N OH HIT O NH N H link N H HIT TARGET 2) washings O NH N H link N H TARGET HIT TARGET identification by MALDI-TOF 3) Hit-biotin-streptavidin on beads: parasitic lysate with TARGET biotin link HN N HIT H biotin link HIT HN N H TARGET 1) 2) washings streptavidin streptavidin biotin link HN N HIT H We present herein the synthesis of the linked hits and the anchorage of this functionalized inhibitor onto various solid supports. TARGET REFERENCES 1. Verhaeghe P., Azas N., Gasquet M., Hutter S., Ducros C., Laget M., Rault S., Rathelot P., Vanelle P. Bioorg. Med. Chem. Lett. 2008; 18: Verhaeghe P., Azas N., Hutter S., Castera-Ducros C., Laget M., Dumètre A., Gasquet M., Reboul J-P., Rault S., Rathelot P., Vanelle P. Bioorg. Med. Chem. 2009; 17: Castera-Ducros C., Azas N., Verhaeghe P., Hutter S., Garrigue P., Dumètr A., Mbatchi L., Laget M., Remusat V., Sifredi F., Raul S., Rathelot P., Vanelle P. Eur. J. Med. Chem. 2011; 46: Verhaeghe P. Dumètr A., Castera-Ducros C., Hutter S., Laget M., Fersing C., Prieri M., Yzombard J., Sifredi S., Rault S., Rathelot P., Vanelle P., Azas N. Bioorg. Med. Chem. Lett. 2011; 21: Primas N., Verhaeghe P., Cohen A., Kieffer C., Dumètre A., Hutter S., Rault S., Rathelot P., Azas N., Vanelle P. Molecules 2012; 17: Kieffer C., Verhaeghe P., Primas N,. Castera-Ducros C., Gellis A., Rosas R., Rault S., Rathelot P., Vanelle P. Sonogashira cross-coupling reaction in 4-chloro-2-trichloromethylquinazoline series is possible despite a side dimerization reaction. Tetrahedron 2013; 69: Knockaert M., Gray N., Damiens N., Chang Y.T., Grellier P., Grant K., Fergusson D., Mottram J., Soete M., Dubremetz J.F., Le Roch K., Doering C., Schultz P.G., Meijer L. Chem. Biol. 2000; 7: Doerig C., Meijer L., Mottram J. Trends Parasitols. 2002; 18: wamlis mizanmimartuli miwodebis sistemebisa da formebis Seswavla da SemuSaveba 1 bakurize a., 2 andreu v., 1 bakurize l., 1 bojaze a., 1 vacnaze v., 3 msvildaze v., 3 lego J. 1 Tbilisis saxelmwifo samedicino universiteti, farmacevtuli teqnologiis departamenti, saqartvelo; 2 marselis xmeltasuazrvis universiteti, safrangeti; 3 Sikutimis universiteti, kanada medikamentozuri Terapiis ert-erti umnisvnelovanesi problemaa organizmistvis wamlebis seleqciuri (mizanmimartuli) miwodebis sakitxi. tradiciuli preparatebis umetesoba moqmedebs samizneze da izleva sasurvel efeqts, amave dros moqmedebs organizmis sxva sistemebze da iwvevs arasasurvel gartulebebs. msoflio jandacvis organizaciis monacemebit 300 mln adamiani daavadebulia astmit. astma aris yvelaze fartod gavrcelebuli qronikuli daavadeba bavsvebsi. 51

52 sainhalacio glukokortikosteroidebi 30 welze metia rac didi warmatebit gamoiyeneba bronqialuri astmit daavadebulta mkurnalobasi. marali efeqturobit gamoirceva am jgufis ert-erti warmomadgeneli flutikazon propionati. sainhalacio samkurnalwamlo sasualebebis efeqturoba mnisvnelovanwilad damokidebulia samizne organomde mizanmimartuli miwodebis sistemebis sworad SerCevasa da gamoyenebis teqnologiebze. dadgenilia, rom Cveulebrivi dozirebuli aerozoluri inhalatorebis gamoyenebis dros sainhalacio glukokortikosteroidebis dozis aranakleb 90% deponirdeba piris RruSi, rac iwvevs preparatis efeqturobis Semcirebas da adgilobrivad piris Rrus kandidozebis ganvitarebas. aranakleb problemuria mukoviscidozi. mukoviscidozi autosomnorecesiuli genetikuri daavadebaa. igi sxvadasxva etnikur jgufsi sxvadasxva sixsirit gvxvdeba. sasualod yovel axaldabadebulsi 1 SemTxvevaa dafiqsirebuli. mukoviscidozis dros parenteralurad gamoiyeneba aminoglikozidebi gentamicinis sulfati. amastan aminoglikozidebis xangrzlivi mirebisas vitardeba iseti gverditi movlenebi, rogoricaa: oto- da nefro-toqsikuroba, Sedegad ziandeba smenis nervi, vitardeba qronikuli siyrue, qronikuli renaluri ukmarisoba, Tavbrusxveva da a.s. mukoviscidozis dros didi warmatebit gamoiyeneba sainhalacio Terapia. igi efuzvneba aerozolis saxit antibiotikebis mizanmimartul miwodebas inhalatorebis gamoyenebit. am dros miirweva antibiotikis maqsimaluri koncentracia filtvis qsovilsi da usafrtxo koncentracia sisxlsi, Sedegad Tavidan acilebulia gverditi efeqtebi. nasromis mizans warmoadgenda: gentamicinis sulfatis sainhalacio fxvnilis recepturisa da teqnologiis SemuSaveba xelsawyo,,hendihaler -isatvis da sainhalacio flutikazon propionatis mizanmimartuli miwodebis sistemebis Seswavla; biofarmacevtuli kvlevebis safuzvelze SemuSavebulia gentamicinis sulfatis sainhalacio, mizanmimartuli miwodebis dozirebuli fxvnilis kompozicia inhalator,,hendihaler -isatvis Semdegi SemadgenlobiT: gentamicinis sulfati mg; hidroqsipropil-metilceluloza mg; natriumis qolati _ 0.05 mg; mowodebulia gentamicinis sulfatis sainhalacio dozirebuli fxvnilis Jelatinis kafsulebsi momzadebis teqnologia; eqsperimentaluri kvlevebis safuzvelze dadgenilia, rom flutikazon propionatis sainhalacio wamlis formis mirebisas, aerozoluri nawilakebis pir-xaxasi deponirebis Sedegad ganvitarebuli gverditi movlenebis Tavidan acilebisa da samizne organosi (bronqialuri xe) maqsimaluri deponirebisatvis mizansewonilia speiserebis: Hexal2, Hexal New da sarqveliani Semakavebeli sivrceebis: AC Max, Vortex-is gamoyeneba; STUDY AND DEVELOPMENT OF TARGETED DRUG DELIVERY SYSTEMS AND DOSAGE FORMS 1 Bakuridze A., 2 Andrew V., 1 Bakuridze L., 1 Bozhadze A., 1 Vachnadze V., 3 Mshvildadze V., 3 Legault J. 1 Tbilisi State Medical University Department of Pharmaceutical Technology, Georgia; 2 University of Aix-Marseille II, Marseille, France; 3 Université du Québec à Chicoutimi, Canada One of the main problems of drug therapy is selective (deliberate) drug delivery to body. Majority of the traditional drugs effect on the target giving the desirable results, but they simultaneously impact on other body systems casing some complications. 52

53 According to World Health Organization 300 million people have asthma. It is widely spread chronic disease in Children. Inhaled Glucocorticosteroids are successfully applied for more than 30 years to heal bronchial asthma. Flutikazon propionate, one of the representatives of this group, is distinguished with high efficiency. Efficiency of inhaled medication mainly depends on proper selection of deliberate delivery systems to the target organ as well as application technology. It is determined that during application of dosed aerosol inhalers at least 90% of the inhaled glucocorticosteroids dose is deposited in the mouth which leads to a decrease in the effectiveness of the drug and the development of oral candidiasis locally. Cystic fibrosis is also problem causing. Cystic fibrosis is an autosomno - recessive genetic disease. It can be found in various frequencies in different ethnic groups. An average 1 case is stated in every newborn babies. Cystic fibrosis is healed with gentamicin sulfate - aminoglycosides taken parenterally. However, long lasting usage of aminoglycosides develops side effects such as Otto and nephron toxicity. It results in damage of auditory nerve, chronic deafness, chronic renal failure, dizziness and etc. Inhalation therapy is widely used to cure cystic fibrosis. It is based on the targeted delivery of antibiotics in the form of aerosol using inhalers. The maximum concentration of antibiotic is achieved in the lung tissue; the safe concentration is observed in the blood. As a result of it, the side effects are avoided. Malignant cancer belongs to the number of the most widespread diseases in the world. Mortality caused by the malignant tumors is presented by disturbing statistical data. As WHO forecast notifies number of victims of malignant cancer will be 9 million in 2015 and 11 million in 2030 approximately. Among all other methods of treatment of cancer chemotherapy tends to be one of the most widely applied means. Out of all types of chemotherapeutic drugs widely used in oncology great part comes from the compounds and derivatives obtained from medicinal plants. With the purpose of increasing the efficiency of anti-cancerous medications significant attention is paid to their targeted delivery to the relevant organ, tissue and cell. High level of selectivity is reached when the active substance of the drug is transporting by the liposomes. By means of endocytosis cytotoxic substance encaplsulated liposome is absorbed by cancerous cell. The force of lysosomes will destroy the system in the cell and cytotoxic substances will be released, which further will ensure the death of cancerous cell. Therefore immobilization of the herbal cytotoxic medications with purpose of selective biopenetration, increasing efficiency and reducing toxicity is the one of the most actual ways for effective and rational treatment of the oncological patients. The aim of this paper is to elaborate the recipe and technology for inhalation powder of gentamicin sulfate for the equipment Handyhaller and to study deliberate delivery systems of inhalation Flutikazon Propionate; immobilization of citotoxic total alkaloids obtained from celandine (Chelidonium majus L.), with purpose to increase the level of selective biopenetration and effectiveness in cancerous cells and decrease the index of toxicity. Based on bio-pharmaceutical researches for deliberate delivery the inhalation powder of gentamicin sulfate for the equipment Handyhaller is developed in the following composition: Gentamicin sulfate 49,45mg; Hidropropil - methyl cellulose 0,5mg; Sodium Cholate _ 0,05mg; Preparation technology of gentamicin sulfate dosed inhalation powder in gelatin capsules is submitted. Experimental research base has been established that in order to avoid side effects of taking of Flutikazon propionate inhaled form and deposition of the aerosol particles in the mouth and to deposit fully in the target organ (Bronchial tree) instead, it is reasonable to employ spacers Hexal2, Hexal New and valve restrictive spaces AC Max, Vortex. By pharmacological researches has been studied cytotoxic activity of total and individual alkaloids obtained from aerial and terrestrial parts of celandine growing in Georgia. 53

54 By mean of technological and pharmacologic researches has been developed innovative liposomal solution, which is characterized by selective cytotoxic activity and is safe for healthy normal cells; Has been developed technologies for obtaining liposomal complex-systems; Has been standardized liposomal substance, active substances of the drug were identified by Gas chromatography-mass spectrometry method (GC/MS). Has been determined concentration of incorporated active substances (for the solution obtained by modified shaking method % and for the solution obtained by ethanol injection method 15.7%), size of the liposome particles (for the solution obtained by modified shaking method nm and for the solution obtained by ethanol injection method nm) and zeta-potential (for the solution obtained by modified shaking method - 42 mv and for the solution obtained by ethanol injection method - 12 mv%). BIOLOGICALLY ACTIVE POLYETHERS FROM DIFFERENT SPECIES OF BORAGINACEAE FAMILY AND THEIR SYNTHETIC DERIVATIVES: PROSPECTIVE THERAPEUTIC AGENTS 1 Mulkijanyan K., 1 Barbakadze V., 1 Gogilashvili L., 1 Amiranashvili L., 1 Merlani M., 1 Novikova Zh., 1 Sulakvelidze M., 2 Bakuridze A., 2 Gokadze S. 1 Tbilisi State Medical University I. Kutateladze Institute of Pharmacochemistry; 2 Tbilisi State Medical University, Department of Pharmaceutical Technology, Georgia For centuries, plants belonging to Boraginaceae family such as Symphytum asperum, S.caucasicum, S.officinale and Anchusa italica have been widely used in folk for treatment of different kinds of disorders and wounds [1-4]. The first representative of a new class of natural polyethers - regular dihydroxycinnamate-derived polymer - poly[oxy- 1-carboxy-2-(3,4-dihydroxyphenyl)ethylene] (POCDPE) (Fig.1) has been detected both in Comfrey (S. asperum, S. caucasicum, S. officinale) and Bugloss (A. italica) species [5,6]. Pharmacological studies of water-soluble highmolecular fractions from the roots and stems of these species containing mainly this dihydroxycinnamate-derived polyether revealed its pronounced biological activity. The present communication summarizes recent data on pharmacological efficacy of POCDPE in treatment wounds and burns. a b Fig. 1. Poly[oxy-1-carboxy-2-(3,4-dihydroxyphenyl)ethylene] (a) and its synthetic monomer (b) Material and methods. Isolation and purification. Air dried roots, stems and leaves ground up and fore-extracted exhaustively in a Soxhlet apparatus using chloroform, methanol and acetone to remove pigments, lipids and low molecular compounds. A hot water extraction was performed followed by dialysis and precipitation in 4 volumes of ethanol or acetone yielded water-soluble crude polysaccharides. Fractionation. S.asperum and S.caucasicum crude polysaccharides from roots, stems and leaves were fractionated by ultrafiltration in an Amicon chamber (Amicon Corp. Lexington MA, USA) under nitrogen pressure (3 atmosphere) using ultrafiltration membrane with cut-off value of 1000 kda (NMWL 1 M Filtron omega series). Extraction/detection of alkaloids. Air-dried ground roots, stems and leaves, crude polysaccharides and high molecular (> 1000 kda) preparations were extracted exhaustively with methanol. Then the alkaloids, applied as 54

55 methanol extracts, were placed on silicagel plates (60 F254, Merk or Silufol F254, Chech Republic). The solvent system: chloroform-methanol-25% ammonia (85:14:1, v/v/v). Runs of 10 cm were usual. Plates were air-dried, sprayed lightly with 30% aqueous hydrogen peroxide and heated at o C for about 15 min. The plates were cooled, sprayed with acetic anhydride reagent, and heated as before for 15 min. Alkaloids were viewed in UV light or detected using Ehrlich s reagent, followed by heating for 5-15 min. Test and reference preparations. Pyrrolizidine alkaloids- and allantoin-free medicinal form has been developed - the 2.5 % ointment of water-soluble fraction of comfrey roots containing crude polysaccharides and POCDPE (C). Reference preparations - 2.5% allantoin ointment (A) and combined ointment (CA) (1.25% crude polysaccharides +1.25% allantoin). 2.5% ointment, containing synthesized monomer of POCDPE (SM) was also tested. Mouse excisional wound model. Two 1 cm diameter skin rags were cut out on depilated skin area [7]. Operation was carried out under ether anesthesia. Treatment of animals began through 24 h after operation. Four groups of 6 animals were randomized and investigated: groups 1, 2, 3 and 4 were treated with C, A, CA and SM ointments, respectively, while group 5 stayed untreated and served as treated/untreated control. Wounds were treated with 0.1 ml of ointment per wound once a day. Rat skin burn model. Standardized IIIA-degree skin burns were induced on depilated skin area using special device with the established temperature scale and contact electrical heater (2 cm 2 square copper plate) [7]. The temperature of a contact plate was 150 o С, exposition time 10 sec. Burn induction was carried out under ether anesthesia. Four groups of 6 animals were randomized and investigated: groups 1, 2 and 3 were treated with (C), (A) and (CA) ointments, respectively, while group 4 was left untreated and served as treated/untreated control. Treatment of animals began immediately after burn induction. Wounds were treated with 0.2 ml of ointment per wound once a day. Estimation of healing process. Clinical supervision over wound healing process was led daily, up to full healing. Wounds were examined for the presence of contamination, exudation, scab formation. Once a week wounds were digitally photographed and the wound area was estimated using ImageJ 1.46-r software. Wound healing effect was estimated by the reduction of injured area in relation to initial and calculated under the formula: D = (S exp / S in ) х 100 % where S in - initial wound area on day 1; S exp - wound area on day of inspection. The obtained data were processed statistically using Student s t-test. Results and discussion. Isolation and purification of POCDPE. In purified extracts of roots, stems and leaves PAs appeared as weak brown spots, fluorescent when viewed in UV light. However, much greater sensitivity was achieved by spraying the plates with Ehrlich s reagent. The compounds were thus separated into three groups with the following Rf values: (a) (highest retention); (b) (medium retention); and (c) (lowest retention) detectable under UV light and according to positive reaction with Ehrlich s reagent. No traces of PAs were detected in water-soluble crude polysaccharides and high-molecular (>1000 kda) preparations after ultrafiltration (Fig. 2). Fig. 2. Detection of PAs using TLC.A raw extracts, B high molecular fractions containing POCDPE: a roots, b stems, c leaves 55

56 Mouse excisional wound model. Wound area in animals, treated with ointments C" "A" and «CA», since day 7 of experiment was significantly less (15, 23 and 45 %, accordingly), than in control group (p<0.01). Scab rejection in groups treated with ointments C" "A" and CA began on day 5, whereas in control - on day 7. In mice treated with ointment CA, full reepithelization was completed 4 days earlier (on day 10), than in animals, treated with ointments C" and "A". Full healing of wounds in control group has come to the end on day 17. The synthetic monomer appeared less effective than natural polyether (Fig. 3). 200 Wound area mm 2 0 control 2.5% POCDPE 2.5% alantoin Fig. 3. Healing effect of 2,5% POCDPE and 2,5% SM ointments (excisional wounds in mice) Rat skin burn model. Burn wound area in animals, treated with ointments C, A" and «CA» since day 2 of the experiment was, correspondingly, 40, 10 and 20% less than in control group (p<0.01) (Fig. 4). Primary eschars in groups C" "A" and CA were torn away on day 8-10, while in control - on day Full healing in animals treated with ointment "A", was achieved 3 day earlier, than in "S" and CA treated animals, and 5 days earlier than in control group. 500 Burn area (mm 2 ) 0 Days Control Fig. 4. Healing effect of 2,5% POCDPE ointment (skin burn in rats) Previously it was established that comfrey crude polysaccharides possess antiexudative activity [4] and, whereas POCDPE, in contrast with both allantoin and pure polysaccharides, exhibits marked antioxidant activity. Moreover, it was established, that POCDPE inhibits the TNF- production by human mononuclear cells/macrophages [5]. Taking all above mentioned into consideration it may be suggested that burn healing effect of the investigated composition results from synergistic action of the constituens on the second phase of wound healing, the inflammatory response. Conclusion The proposed isolation scheme permits to remove completely the toxic PAs from the plant raw material. Wound healing activity of ointment containing POCDPE by efficiency does not yield to 2.5% allantoin ointment, whereas in skin burn model it appears fourfold active than allantoin ointment and twice active than combined ointment containing 1.25% each POCDPE high-molecular fraction and allantoin. The obtained results allow assuming with high degree of reliability, that healing activity of comfrey preparations could be associated not only with allantoin but also with POCDPE. The established pharmacological action of ointment allows recommending it for treatment of wounds and second and third-degree burns. Acknowledgments. This work has been fulfilled by financial support of the Shota Rustaveli National Science Foundation Grants #ST and #AR

57 REFERENCES 1. Gviniashvili Ts.N. The Caucasian species of the genus Symphytum L. Tbilisi: Metsniereba; 1976: 145, ( ). 2. Awang D.V.C. The American Herb Association, Quarterly Newsletter 1989; 6(4): Rode D. Trends Pharmacol. Sci. 2002; 23 (11): van den Dungen F.M. Symphytum officinale L. Influence on immune functions and wound-healing processes. Ph.D. Thesis. Utrecht Univ. 1993; Barbakadze V., Kemertelidze E., Targamadze I., Mulkijanyan K., Shashkov A.S., Usov A. I. Molecules 2005; 10(9): Barbakadze V., Merlani M., Amiranashvili L., Gogilashvili L., Mulkijanyan K. Study of Poly[Oxy-1-Carboxy- 2-(3,4-Dihydroxyphenyl)Ethylene] From Symphytum asperum, S.caucasicum, S.officinale, Anchusa italica by Circular Dichroism. Bull. Georg. Natl. Acad. Sci. 2012; 6(1): Wound Healing: Methods and Protocols, L.A. DiPietro, A.L. Burns (Eds.); Humana Press, Inc., Totowa, NJ, USA: 2003; 467. SUMMARY BIOLOGICALLY ACTIVE POLYETHERS FROM DIFFERENT SPECIES OF BORAGINACEAE FAMILY AND THEIR SYNTHETIC DERIVATIVES: PROSPECTIVE THERAPEUTIC AGENTS 1 Mulkijanyan K., 1 Barbakadze V., 1 Gogilashvili L., 1 Amiranashvili L., 1 Merlani M., 1 Novikova Zh., 1 Sulakvelidze M., 2 Bakuridze A., 2 Gokadze S. 1 Tbilisi State Medical University I. Kutateladze Institute of Pharmacochemistry; 2 Tbilisi State Medical University, Department of Pharmaceutical Technology, Georgia Extracts from the plants belonging to Boraginaceae family Symphytum asperum, S.caucasicum and Anchusa italica have been used in folk medicine in the treatment of some kinds of disorders, mainly fractures and wounds. Aforenamed extracts contain allantoin, claimed to be a cell proliferation-stimulating agent responsible for the wound-healing properties of Symphytum, and, on the other hand, hepatotoxic pyrrolizidine alkaloids which strongly restrict internal use of comfrey extracts. Allantoin- and toxic pyrrolizidine alkaloids-free composition containing polysaccharides and novel biopolymer from the roots of aforesaid plants poly[oxy-1-carboxy-2-(3,4- dihydroxyphenyl)ethylene] POCDPE was studied to appraise its pharmacological properties in in vivo experiments (mouse excisional wound and skin burn models). Besides, a monomer of POCDPE was synthesized and examined in excisional wound model. Ointment, containing 2.5% polysaccharides and POCDPE was found to have pronounced wound-healing properties and by efficacy it does not yield to 2.5 % allantoin ointment. Synthetic monomer also exhibited wound healing activity, but its efficacy appeared lower than that of the natural polyether. The obtained results allow assuming that wound healing activity of comfrey preparations could be associated not only with allantoin but also with POCDPE. Keywords: Boraginaceae, wound healing, poly[oxy-1-carboxy-2-(3,4-dihydroxyphenyl)ethylene], allantoin, pyrrolizidine alkaloids. reziume ojaxi BORAGINACEAE-s zogierti saxeobis biologiurad aqtiuri polieterebi da mati sintezuri warmoebulebi: perspeqtiuli Terapiuli agentebi 1 mulkijaniani k., 1 barbaqaze v., 1 gogilasvili l., 1 merlani m., 1 amiranasvili l., 1 novikova J., 1 sulaqvelize m., 2 bakurize a., 2 goqaze s. 1 Tbilisis saxelmwifo samedicino universiteti i. qutatelazis farmakoqimiis instituti; 2 Tbilisis saxelmwifo samedicino universiteti, farmacevtuli teqnologiis departamenti, saqartvelo 57

58 ojaxi Boraginaceae-s saxeobebis Symphytum asperum, S. caucasicum da Anchusa italica-s eqstraqtebs xalxur medicinasi uzvelesi droidan iyenebdnen sxvadasxva saxis daavadebebis samkurnalod, kerzod motexilobebis da Wrilobebis Sesaxorceblad. arnisnuli eqstraqtebi Seicaven ujredis proliferaciis mastimulirebel agents alantoins, romeltan asocirdeba zemot xsenebuli Tvisebebi, da, meores mxriv, hepatotoqsikur pirolizidinis alkaloidebs, romlebic Zlier zrudaven am eqstraqtebis Sinagan gamoyenebas. xsenebul mcenareta fesvebidan mirebulia alantoinis da pirolizidinis alkaloidebisagan Tavisufali polisaqaridebis jamis da axali biopolimeris poli[oqsi-1-karboqsi-2-(3,4-dihidroqsifenil)etileni] (pokdfe) kompozicia da Sefasebulia misi farmakologiuri Tvisebebi in vivo (Wrilobis da kanis damwvrobis modeli) eqsperimentsi. garda amisa, sintezirebulia pokdfe-s monomeri. dadgenilia, rom pokdfe Semcveli 2.5% malamo Wrilobis Semaxorcebeli efeqturobit utoldeba alantoinis 2.5% malamos. Seswavlil eqsperimentul modelze bunebrivi polimeri sintezur monomerze ufro aqtiuri armocnda. mirebuli Sedegebidan gamomdinare, cxadia, rom lasqaras preparatebis Wrilobis Semaxorcebel unars ganapirobebs ara mxolod alantoini, aramed aseve pokdfe. nasromi Sesrulebulia rustavelis erovnuli samecniero fondis mier dafinansebuli samecniero sagranto proeqtis # AR/109/8-403/11 farglebsi. saqartvelos floris zogierti saxeobis meoreuli metabolitebi: fundamenturi da gamoyenebiti aspeqtebi alania m., SalaSvili q., sarareisvili T., qavtaraze n., sutiasvili m. Tbilisis saxelmwifo samedicino universiteti, iovel qutatelazis farmakoqimiis instituti, saqartvelo saqartvelos floris 1386 saxeobis mravalwliani winaswari gamokvlevebit gamovlenilia meoreuli metabolitebit mdidari saxeobebi. perspeqtiul mcenareta Rrma qimiuri gamokvlevis safuzvelze izolirebulia 400-mde flavonoidi flavonebis (apigenini, luteolini), flavonolebis (kemperoli, kvercetini. izoramnetini, miricetini), flavanonolebis (7-metoqsi-aromadendrini), xalkonebis, auronebis da izoflavonebis jgufidan. mat Soris 40-mde axali flavonoidi da 22 cikloartani [1]. mcenareebi Melilotus officinalis, Pueraria hirsuta, Trifolium hibridum, Vinca herbacea, Robinia pseudacacia, Astragalus falcatus armocndnen flavonoid robininis Semcveli. mat Soris Astragalus falcatus Si robininis Semcveloba 2%-s awarbebs, Pueraria hiorsuta Si 1 %-mdea, Robinia pseudacacia-si 0.5%. robininis mnisvnelovani SemcvelobiT Astragalus falcatus-i hipoazotemiuri da diurezuli moqmedebis preparat flaroninis nedleulia, Pueraria hirsuta - damatebiti nedleuli [2,3]. namgalnayofa astragali (Astragalus falcatus) garda robininisa Seicavs hidrofilur flavonoidur glikozidebs, romelta gamoyofa mcenaridan da substanciidan rtuli amocanaa. am naertebis individualizacia SesaZlebeli Seiqmna preparatuli qq da maralefeqturi sitxovani qromatografiis gamoyenebit. Sedegad izolirebula 5 oligozidi- falkozidebi A, B, C, D, E. falkozidebi A, B da E armocndnen kempferolis tetra- da pentaozidebi. sruli arnagoba dadgenilia falkozid C - da D-sTvis [1,4]. 58

59 OH OH OCH 3 O OH OH H O HO OH O OH OH O O O O H 3 C HO HO O OH O OH OHO O O O H O HO OH H 3 C HO O OH O O O HO OH OH falkozid C H O HO H 3C H O O OH O falkozid D O OH HO O OH Astragalus galegiformis galegisebri astragali aris nedleuli maralefeqturi flavonoiduri glikozidebisa: astragalegozidi- diurezuli, izoastragalegozidi - hipoazotemiuri, diurezuli da hipoglikemiuri [2]. H OH H O HO O O HO H OH H H O OH O izoastragalegozidi OCH 3 OH OHH O H OH OH HO H H H HO OH O O O O H HO H OCH 3 H H O OHH OH OH O H HO H H H OHH OH OH astragalegozidi mcenaris fotlebis hidrofiluri laqidan gamoyofilia sxvadasxva polarobis da bunebis flavonoidebi: kempferoli, astragalini da oligozidebi: flagalozidebi A E. sruli arnagoba dadgenilia C da D flagalozidebisatvis. OCH3 OH OH OH HO O HO O O OH O CH2 OH O O OH O CH3 OH O OH O OH OH OH OH flagalozid C O OH O O OH OH O O OH OH OH flagalozid D Astragalus microcephalus marali leikopoezuri aqtivobisaa, Seicavs sxvadasxva jgufis naertebs. misgan gamoyofilia 7-hidroqsiflavoni, izoflavoni kalikozini, kempferol 3 ramno-qsilozidi, 6,3',4'- trihidroqsi auroni sulfuretini da 2',4',4 trihidroqsi xalkoni [1]. fenoluri naertebis rolze mcenaresi miutitebs Hedera colchica s flavonoidebis struqturis cvlileba sezonis mixedvit. SemCneuli iqna, rom mcenare zamtarsi ifereba witlad. zafxulisa da zamtris nimusebis SedarebiTi analizit dadgenilia, rom zafxulis periodsi mcenare asintezirebs rutins (0.57%), zamtarsi ki antocianur pigments cianidin-3-rutinozids (0.52%), romelic glikozid rutinis ardgenili formaa. es monacemebi adasturebs literaturul monacemebs, flavonolebisa da antocianebis monatesaobaze da im faqts, rom zamtarsi mcenaris damcveli funqciis gazliereba antocianebs ukavsirdeba [5]. Koelreuteria paniculata mdidari armocnda triterpenuli naertebit. mati Seswavlisas gamoyofil iqna fenoluri naertebis fraqcia, romlis dayofitac izolirebuli iqna 59

60 acilirebuli flavonoiduri heqsaozidi [1]. es naerti am saxeobidan pirveladaa izolirebuli. Trifolium-is jams armoacnda gonadotropuli aqtivoba. jamis mtavari Semadgeneli komponentebia izoflavonebi [6]. Trifolium hybridum armocnda hiperinis mdidari wyaro, romelsac saintereso kardiotonuri aqtivoba axasiatebs. SavizRvispireTSi introducirebuli Eupatorium micrantum mdidaria flavanonoluri naertebit (4%). misgan gamoyofili ori urtiertizomeruli glikozidi axal naertebs warmoadgenen. isini Zlieri antioqsidanturi da proliferaciul-mastimulirebeli aqtiurobit xasiatdebian Jurkat ujredebis mimart [7,8]. H 3 CO H O OH H 3 CO H O 2 OH OH H RO O mikrantozidi OH H RO O neomikrantozidi 3 R= D-glukoza gvari Verbascum-is saxeobebi gamoircevian iridoiduli naertebis SemcvelobiT. gamoyofilia 4 individi, sruli arnagoba dadgenilia ori naertistvis. erti matgani harpagozidia, meore axali dimeruli naertia, romelsac laqsozidi vuwodet (gamouqveynebeli masalebi). O C O OCH 3 HO H 3 CO O OH O HO O OH D-gal 6' CH2 O O OH OH OH O OH O D-glc CH 2 C O laqsozidi nivtierebata strurturis dadgenas vaxdendit fizikur-qimiuri Tvisebebis SeswavliT, gardaqmnis produqtebis mirebit da speqtruli analizit iw-, ui-, 1 H, 13 C bmr speqtroskopiit, mati 2D eqsperimentebit, mas- speqtrometriit. calkeuli individebisatvis da mati jamuri preparatebisatvis dadgenilia marali antioqsidanturi hipoglikemiuri, hipoazotemiuri, leikemiis sawinaarmdego, hipoqolesterinemuli, androgenuli, estrogenuli, kardiotonuri da sxva efeqtebi in vivo cdebsi. jamuri preparatebis mtavari Semadgeneli komponentebia flavonoidebi, fenolkarbomjavebi, aminomjavebi, cikloartanebi, romlebic xasiatdebian gansxvavebuli farmakologiuri efeqtit. cikloartanebi mravalmxrivi biologiuri aqtivobit xasiatdebian. magalitad ciklogalegigenini da misi glikozidebi avlenen leikicitebis proliferaciis unars, hopoqosterinemul da kardiotonur aqtivobas, diurezul da diabeturi nefropatiis O 60

61 samkurnalo efeqts, amarleben imunur gamzleobas da Trgunaven RviZlisa da tvinis simsivnuri ujredebis ganvitarebas [2,9,10]. O OH H OH ciklogalegigenini es naertebi ZiriTadi Semadgenelia preparat flaroninis warmoebis narcenebisa, romelic gatvaliswinebulia hopoazotemiuri, hipoglikemiuri, kardiotonuli da diurezuli moqmedebis kvebis danamatis SesamuSaveblad. flaroninis warmoebis narcenebidan mirebulia kempferoli (gamosavali 0.5%), romelic mowodebulia ertis mxriv, rogorc standarti flavonoidebis analizsi da meores mxriv, rogorc hipoglikemuri moqmedebis aqtiuri substancia. kempferolis hipoglikemuri aqtivoba (22.29%) farmacvtul bazarze arsebuli samkurnalo preparatebis butamidis (20.10%), qlorpropamidis (24.10%) Sualeduria. yvela savaraudo preparatisatvis SemuSavebulia analizis metodebi da teqnikuri dokumentacia. literatura HO OH 1. Алания М.Д., Шалашвили К.Г., Кавтарадзе Н.Ш., Сагареишвили Т.Г., Сутиашвили М.Г.Фенольные соединения некоторых растений флоры Грузии: структра, физико-химические свойства, биологическая активность. Материалы докладов VIII международного Симпозиума «Фенольные соединения, фундаментальные и прикладные аспекты». 2-5 октября, М.: 2012; Алания М.Д., Кемертелидзе Э.П., Комиссаренко Н.Ф. Флавоноиды некоторых видов Astragalus L., Флоры Грузии. Монография. Тб.: Мецниереба; 2002: Кемертелидзе Э. П., Сыров В.Н.,Алания М. Д., Кавтарадзе Н.Ш., Хушбактова З.А., Чкадуа Н.Ф., Баджелидзе Л.С. Химический состав и фармакологические активность листьев Pueraria hirsuta (Thunb.) Matsum. D В кн.: Фитохимическое и растениеводческое исследование некоторых растений, произрастающих в Аджарии. Тб.: 2010; Алания М.Д, Кавтарадзе Н.Ш., Схиртладзе А.В., Сутиашвили М.Г.. Флавоноидные олигозиды Astragalus falcatus флоры Грузии. Химия природ.соедин. 2011; 3: Алания М.Д., Комиссаренко Н.Ф., Кемертелидзе Э.П. Флавоноиды Astragalus falcatus. Мецниереба. Сообщ. АН ГССР, 1972; 68: Шалашвили К.Г., Польшин В.В., Кемертелидзе Э.П. Некоторые биологические особенности суммы флавоноидов Trifolium hybridum. Тезисы III Всес. Сим. по фенольным соединениям. Тб.: Мецниереба; май 1976: Сагареишвили Т.Г., Цицишвили В.Г. Энантиомер микрантозида. Химия природ.соединений 2006; 4: Сагареишвили Т.Г., Микаутадзе М.М., Инцкирвели Н.А., Енукидзе М.Г., Мачавариани М.Г. Фармакологическая активность флавоноидного гликозида из листьев растения Eupatorium micranthum Less., интродукцированного в Грузии. Медицинские новости Грузии 2008; 4(157): Luisella Verotta, Marco Guerrini, Nadia El-Sebakhy, Aya M. Assad, Saad M. Toaima, Mohamed M. Radwan, Yang-Ge Luo, John M. Pezzuto.Cycloartane and oleanane saponins from Egyptian Astragalus spp. as Modulations of Lymphocyte Proliferation. Planta med. 2002; 68: alania m.. Astragalus is saxeobebis cikloartanuli naertebi. meore samecniero konferencia bunebrivi da sintezuri biologiurad aqtiuri nivtierebebi, noemberi 2013; Tb: 2013;

62 reziume saqartvelos floris zogierti saxeobis meoreuli metabolitebi: fundamenturi da gamoyenebiti aspeqtebi alania m., SalaSvili q., sarareisvili T., qavtaraze n., sutiasvili m. Tbilisis saxelmwifo samedicino universiteti, iovel qutatelazis farmakoqimiis instituti, saqartvelo saqartvelos floris saxeobebis winaswari fitoqimiuri analizit gamovlenilia meoreuli metbolitebit mdidari perspeqtuli saxeobebi. zogierti matganis Rrma qimiuri SeswavliT gamoyofilia 400-mde flavonoidi, 100-ze meti sxvadasxva klasis naerti. mat Soris axali 38 flavonoidi da 22 cikloartani. zogierti saxeoba mowodebulia, rogorc flavonoiduri naertebis nedleuli: Astragalus falcatus, Pueraria hirsuta, A. galegiformis, Eupatorium micranthum, Trifolium hybridum da sxva. gamoyofili individebis qimiuri Seneba dadgenilia kvlevis Tanamedrove fizikurqimiuri da speqtruli analizis metodebit iw-, ui-, 1 H da 13 C bmr- speqtroskopiit, 2D eqsperimentebit da mas- spetrometriit. individualuri da jamuri preparatebisatvis gamovlenilia antioqsidanturi, hipoglikemiuri, hipoazotemiuri, kardiotonuri, leikopoezuri, hipoqolesterinemuli diurezuli efeqtebi in vivo cdebsi. perspeqtuli savaraudo preparatebisatvis SemuSavebulia analizis metodebi da teqnikuri dokumentaciis proeqtebi. SUMMARY SECONDARY METABOLITS FROM SOME PLANTS OF GEORGIAN FLORA: FUNDAMENTAL AND USING ASPECTS Alania M., Shalashvili K., Sagareishvili T., Kavtaradze N., Sutiashvili M. Tbilisi State Medical University, Iovel Kutateladze Institute of Pharmacochemistry, Georgia The perspective species of secondary metabolits were revealed by preliminary phytochemical study of Georgian flora. Some of them by deep chemical study were seperated till 400 induvidual flavonoids, over 100 of different clases names; 38 of them new flavonoids and 25 cycloartanes. Some species were selected as a receve survey the flavonoid compounds. For example: Astragalus falcatus, Pueraria hirsuta, A. galegiformis, A. galegiformis, Eupatorium micranthum, Trifolium hybridum and all. The chemical struqtures flavonoids were established by the modern research of the physical-chemical and spectral analysis methods IR-, UV-, 1 H and 13 C NMR spectroscopy, 2D experiments and mass-spectrometry. Pharmacological study of the individual compounds and summer preparation in vitro experiments showed a high antioxydant, hypoglicemic, cardiotonic, hypoazotemic, diuretic, leucopoietic, hypocholesterinemic activitis. The analytical methods and technical documentation has been elaborated for the perspective compounds. 62

63 awaris regionsi gavrcelebuli mineraluri resursebis kvleva medicinasi gamoyenebis miznit miqaia g., masiukovici T., gafrindasvili a., kakulia n., qurdiani n., alavize z., kamkamize g., bakurize a. Tbilisis saxelmwifo samedicino universiteti, farmacevtuli teqnologiis departamenti, saqartvelo bunebrivi samkurnalo faqtorebis gamoyeneba sxvadasxva daavadebebis mkurnalobisa da profilaqtikis miznit ert-erti aqtualuri amocanaa Tanamedrove medicinisatvis. mkurnalobis balneologiuri metodebis danergva rogorc kurortebze, aseve mis garet xels uwyobs mosaxleobis janmrtelobis mdgomareobis efeqtur gaumjobesebas. samkurnalo talaxebs (peloidebs) Tavisi didi Terapiuli moqmedebis gamo balneologiasi da kurortterapiasi gansakutrebuli adgili ukaviat. mati gamoyenebis istoria uxsovari droidan iwyeba. saqartvelos sxvadasxva regionsi Seswavlilia bentonituri Tixebis 19 sabado. mat Soris, mxolod guriis regionis Tixa-askane gamoiyeneba samkurnalo, profilaqtikuri da kosmetikuri sasualebebis saxit, rbil da mkvriv wamaltformebsi ki rogorc damxmare sasualeba. literaturasi ar gvxvdeba monacemebi awaris regionsi gavrcelebuli peloidebisa da Tixebis samedicino praqtikasi gamoyenebis Sesaxeb. kvlevis mizans Seadgenda awaris regionsi gavrcelebuli mineraluri resursebis (peloidebi, Tixebi) kvleva samedicino praqtikasi gamoyenebis miznit. Catarebuli kvlevebis safuzvelze dadgenilia peloidebisa da Tixebis adgilmdebareobebi awaris regionsi, monacemebi datanilia awaris regionis wiariseuli simdidreebis amsaxvel ruqaze; Seswavlilia 63 peloidis da 10 Tixis qimiuri Semadgenlobebi mikro- da makroelementebis Semcvelobaze; gansazrvrulia peloidebis fizikur-qimiuri da teqnologiuri Tvisebebi; peloidebsi ZiriTad moqmed nivtierebebad micneulia huminis mjaveebi; Sedgenilia zogadi teqnikuri pirobebi sulfidur peloidebze; Seswavlilia nifis, gasalianis, Sratianis, WaxaTisa da kvirikes peloidebis antioqsidanturi aqtiurobebi in vitro cdasi; WaxaTisa da kvirikes peloidebsi dadgenilia baqteriofagebis arseboba, romeltac gaacniat stafilokokisa da nawlavis Cxiris lizirebis unari; dadgenilia WaxaTisa da kvirikes peloidebis usafrtxoeba; biofarmacevtuli kvlevebis Sedegad Tixa besumi mowodebulia rogorc fuze-matarebeli rbil wamaltformebisatvis Tixa-askanes nacvlad Teimurovis pastasi. SemuSavebulia rekomendaciebi Seswavlili peloidebis balneologiur praqtikasi gamoyenebaze. SUMMARY THE STUDY OF THE MINERAL RECOURSES SPREAD IN ADJARA REGION FOR THE PURPOSE OF THEIR USE IN MEDICINE Miqaia G., Masiukovichi T., Gaprindashvili A., Kakulia N., Qurdiani N., Alavidze Z., Kamkamidze G., Bakuridze A. Tbilisi State Medical University, Department of Pharmaceutical Technology, Georgia The use of the natural healing factors for the treatment and prevention of various diseases presents the one of the 63

64 current tasks for the modern medicine. The implementation of the balneological methods of treatment in the resorts, as well as outside of them, promotes the effective improvement of the health status of the population. The healing muds (peloids) have a special role in balneology and resort therapy due to their therapeutic action. The history of their use begins from the ancient times. The 19 layers of bentonite clays have been studied in the various regions of Georgia. Among them only Askana clay obtained in Guria region is used in the form of the medicinal, preventive and cosmetic preparations, in the soft and hard pharmaceutical products even as adjunctive agent. In the literature there is found no data regarding the use in medical practice of peloids and clays spread in Adjara Region. The aim of our research was to study the mineral resources spread in Adjara region for the purpose of their use in medical practice. On the basis of the experimental studies: there are stated the locations of the peloids and clays in Adjara region, the data is marked on the map of the mineral wealth of Adjara region; there are investigated the chemical compositions on micro and macro elementary contents of 64 peloids` and 2 clays` samples; there are defined the physical - chemical and technological properties of peloids; in the peloids the main active ingredient is considered huminic acids; there are compiled the general technical conditions of sulphide peloids; there are studied the antioxidant activities of Niphi, Gasaliani, Shratiani, Chakhati and Kvirike peloids using in vitro trial; there is established the presence of bacteriophages in Chakhati da Kvirike peloids, which have the ability of the lyses of E. Coli and Staphylococcus; the safety of Chakhati da Kvirike peloids is ascertained; based on the biopharmaceutical studies there was determined the possibility of using the Beshumi clay as the base-wearing agent in the soft pharmaceutical products instead of Ascana Clay in Teimurovi paste. There are developed the recommendations of using the studied peloids in the balneological practice. There are developed the recommendations of using the studied peloids in the balneological practice. nasromi Sesrulebulia rustavelis erovnuli samecniero fondis mier dafinansebuli samecniero sagranto proeqtis # AR/269/8-403/11 farglebsi. farmakozedamxedvelobis da wamalta gverditi movlenebis monitoringis principebi jibuti S., CafiCaZe z., gongaze n., gorgaslize n. saqartvelos, Sromis, janmrtelobisa da socialuri dacvis saministro ssip samedicino saqmianobis saxelmwifo regulirebis saagento; Tbilisis saxelmwifo samedicino universiteti, samedicino farmakologiis da farmakoterapiis departamenti, saqartvelo wamalta usafrtxoebis uzrunvelyofa msoflios mraval qveyanasi mnisvnelovan problemad gvevlineba, vinaidan farmacevtuli produqciis moxmarebit gamowveuli adamianis janmrtelobis mdgomareobis gauaresebis SemTxvevaTa arwera, registracia da satanado RonisZiebebis gatareba specifikur organizaciul mxarestan aris asocirebuli. mravali fartod gavrcelebuli Tanamedrove farmacevtuli produqti zogjer garkveul sasisroebas warmoadgens adamianis janmrtelobistvis. amastan dakavsirebuli mosazreba pirvelad gamotqmuli iyo 1961 wlis 16 dekembers, Jurnal,,LANCET -Si, sadac avstralieli doqtori braidi gvamcnobda, rom man Cvil bavsvebsi 64

65 SeniSna defeqturi kidurebis sixsiris zrda, rac misi azrit, gamowveuli iyo dedis mier sazile-sedaciuri wamlis,,thalidomide -is mirebit. zemoarnisnulma publikaciam preparatis teratogenuri moqmedebis Sesaxeb Sesabamisi zegavlena moaxdina farto sazogadoebaze, ris Semdegac daiwyo am mimartebit gamosavlis Zieba. mraval qveyanasi Seiqmna sistema, romelic uzrunvelyofda wamlis gverditi movlenebis Sesaxeb yovelgvari informaciis Segrovebis SesaZleblobas. arnisnul sistemas ADR Monitoring system (wamalta gverditi movlenebis monitoringis sistema) ewoda. es organizaciebi pirvelad Seiqmna: avstraliasi, italiasi, axal zelandiasi, niderlandebsi, SvedeTSi, inglissi, amerikis SeerTebul Statebsa da germaniasi. msgavsi sistemebi amjamad arsebobs msoflios mrval ganvitarebul Tu ganvitarebad qveyanasi wels, 10 qveynis warmomadgenlebma - avstraliidan, evropidan da CrdiloeT amerikidan miarwies konsensuss, rata wamalta gverditi movlenebis irgvliv SeegrovebinaT yvela informacia, romelic SemdgomSi gadaecemoda saertasoriso centrs da misi dafinanseba ganxorcieldeboda msoflio jandacvis organizaciis mier. bunebrivia, rom farmacevtuli mrewvelobis da mecnierebis ganvitareba moitxovs Cvens yuradrebas, adeqvatur reaqcias da badebs axal SekiTxvebs wamlis gverditi efeqtebis monitoringis irgvliv. mraval qveyanasi SeimCneva TviTmkurnalobis tendenciebi da iseti farmacevtuli produqtebis advilad xelmisawvdomoba, romlebic unda gamoiyenebodnen mxolod receptit. amastan dakavsirebit ibadeba kitxva: ra Sedegi SeiZleba mohyves yovelive amas pacientta usafrtxoebis TvalsazrisiT?! aseve sayuradreboa is faqtic, rom msoflios wamalta bazarze xorcieldeba falsificirebuli medikamentebis Semodineba. wamlis satanado monitoringi xelsuwyobs aseti produqtebis gamovlenas da mosaxleobis dacvas uxarisxo da gauvargisebuli medikamentebisgan. msoflios mraval qveyanasi farmacevtuli bazris asortimentisa da wamalta moxmarebis ganuxreli zrda, mat mier gamowveul dadebit efeqtebtan ertad mtel rig SemTxvevebSi ganapirobebs gverditi movlenebis ganvitarebis maral risks, rac moitxovs Sesabamisi prevenciuli RonisZiebebis gatarebas, msoflio jandacvis organizaciisa da sxva saertasoriso organizaciebis rekomendaciebis gatvaliswinebas da ganxorcielebas samkurnalo sasualebata postregistraciuli da postmarketinguli monitoringis irgvliv. farmako zedamxedveloba uzrunvelyofs yvela qveyanasi wamlis gverditi moqmedebebis SemTxvevebisa da wamlebtan dakavsirebuli problemebis gadawras, romlebic gansxvavebulia TiToeuli qveynistvis (qveynebis regionebs Sorisac ki arsebobs garkveuli saxesxvaobebi). samkurnalo sasualebebis gverditi movlenebis sixsires ganapirobeben Semdegi faqtorebi: farmacevtuli produqtis warmoeba; distribucia da gamoyeneba/moxmareba (mag: Cvenebebi, doza, xelmisawvdomoba); adgilobrivad warmoebuli samkurnalo sasualebebis xarisxi da Semadgenloba (damxmare nivtierebebi); tradiciuli medikamentebis (mcenareuli sasualebebi) gamoyeneba, romlebmac SesaZloa gamoiwvion specifikuri toqsikuri efeqtebi sxva preparatebtan kombinaciasi da/an monoterapiis saxit; TviTmkurnaloba; araracionaluri farmakoterapia; polipragmazia. 65

66 zemoarnisnulidan gamomdinare, statiasi warmodgenilia sayoveltaod ariarebuli principebi, romlebic sawiroa farmakozedamxedvelobis gasazliereblad da wamlis gverditi movlenebis monitoringis optimizaciistvis, kerzod: wamlis gverditi movlenebis monitoringi, romelic farmakozedamxedvelobis sistemis ert-erti ZiriTadi komponentia farmacevtuli produqtebis usafrtxoebis SefasebisTvis da postmarketinguli zedamxedvelobistvis; msoflio jandacvis organizaciis wamalta usafrtxoebis programis koncefciis gatvaliswineba; registrirebuli medikamentebis racionaluri da instruqciis Sesabamisad gamoyenebis uzrunvelyofa misi xarjt-efeqturobis gazrdis miznit; sasicocxlod aucilebeli esenciuri medikamentebis nusxis Sedgena, qveyanasi yvelaze gavrcelebuli daavadebebis samkurnalod, mkurnalobis racionalizaciisa da optimizaciistvis, agretve xarjt-efeqturi recepturis sistemis misarebad da wamlebit gamowveuli avadobis da sikvdilianobis Tavidan acilebis miznit. farmakozedamxedvelobis ZiriTadi principebia: a) wamlis gverditi moqmedebis irgvliv informaciis Segroveba samedicino da saaftiaqo dawesebulebebis da pacientebis mesveobit; b) wamlis gverditi moqmedebis (ADR) spontanuri Setyobinebis sistemis optimizacia, rac itvaliswinebs: wamlis gverditi movlenebis Sesaxeb mirebuli informaciis analizs da registrirebuli farmacevtuli produqtebis usafrtxoebis profilis Sefasebas; wamlis receptis sistemit gamoweris da SemdgomSi moxmarebis statistikis gansazrvra da Sefaseba samedicino servisebis sxvadasxva doneebze; wamlis gverditi movlenebis Sesaxeb Segrovebuli informaciis damusaveba specialur formatsi; specialur formatsi damusavebuli informaciis gadagzavna janmo-s wamlebis monitoringis saertasoriso TanamSromlobis centrsi; saertasoriso gamocdilebidan gamomdinare, farmakozedamxedvelobis principebis praqtikasi realizacia, farmacevtuli produqtebis usafrtxoebis Sefaseba da postmarketinguli zedamxedveloba qveynis teritoriaze itvaliswinebs qvemot CamoTvlil mosalodnel Sedegebs, rogoricaa: farmakozedamxedvelobis musaobis xarisxis gazrdas da gaumjobesebas; janmrtelobis dazianebis riskebis Semcirebas da pacientta mkurnalobis xarisxis gaaumjobesebas; medikamentebis usafrtxoebis da riski-sargeblianobis Tanafardobis analizis uzrunvelyofas pacientta mkurnalobis msvlelobisas; informaciis Segrovebis SesaZleblobas wamlis usafrtxoebis Sesaxeb, rac,ytavis mxriv, mosaxleobis janmrtelobis mdgomareobis gauaresebis prevenciis garantiaa; wamalta gverditi movlenebis monitoringis sistemis amusaveba mnisvnelovan SeRavaTs azlevs mosaxleobas wamalta xarjt-efeqturobis TvalsazrisiT; saxelmwifos ezleva SesaZlebloba Seamciros sabiujeto xarjebi wamalta araracionalur da araefeqtur gamoyenebastan dakavsirebit; marali riskis mqone preparatebis gamoyenebis Semcirebis safuzvelze SesaZlebeli xdeba sabiujeto dafinansebis da sayoveltao sadazrveo sistemaze gaweuli danaxarjebis Semcireba. daskvna: mimdinare procesebis fonze usafrtxo Terapia gulisxmobs 3 mimartulebis realizacias ertdrouli amoqmedebit, kerzod: 1) wamlis gverditi movlenebis Setyobinebis sistemis implementacia; 2) wamlis moxmarebis mokvleva (receptit gamowera da moxmareba/xarjva) da 66

67 3) usafrtxo da racionaluri medikamentebis gamoyenebis xelsewyoba publikaciebis sasualebit. amgvari musaobis principebi yvelgan emyareba msoflio jandacvis organizaciis da ufsalas monitoringis centris gaidlainebs -,,Guidelines for setting up and running a Pharmacovigilance Centre (Copyright 2000 the Uppsala Monitoring Centre, ISBN X), romelic miznad isaxavs farmacevtuli produqtebis usafrtxoebis monitorings. reziume farmakozedamxedvelobis da wamalta gverditi movlenebis monitoringis principebi jibuti S., CafiCaZe z., gongaze n., gorgaslize n. saqartvelos, Sromis, janmrtelobisa da socialuri dacvis saministro ssip samedicino saqmianobis saxelmwifo regulirebis saagento; Tbilisis saxelmwifo samedicino universiteti, samedicino farmakologiis da farmakoterapiis departamenti, saqartvelo statiasi warmodgenilia farmakozedamxedvelobis principebi da wamlta usafrtxo gamoyenebastan dakavsirebuli RonisZiebebi, romlebic emyareba msoflio jandacvis organizaciis (janmo) rekomendaciebs. massi gaanalizebulia wamlebis araracionalur gamoyenebastan asocirebuli potenciuri riski da am ukanasknelis prevenciis RonisZiebebi. statiis avtorebi miutiteben wamalta gverditi movlenebis monitoringis aucileblobis Sesaxeb, rac gulisxmobs: spontanuri Setyobinebebis sistemis arsebobis aucileblobas, kompilirebuli informaciis analizs da wamlis usafrtxoebis profilis Sefasebas, receptis institutis introducirebis etapebs, gverditi movlenebis Sesaxeb Segrovebuli informaciis damusavebas specialur formatsi da Sesabamisi korespondenciebis mesveobit ufsalas gverditi movlenebis saertasoriso centrtan urtiertkavsirs. amastan, statiasi ganixileba farmakozedamxedvelobis principebtan dakavsirebuli poziciebi, rogoricaa wamalta postregistraciuli monitoringi, wamlis riski-sargeblianobis Tanafardobis analizi da wamlis mirebit gamowveuli riskis Semcirebis prevenciis gzebi. SUMMARY THE PRINCIPLES OF PHARMACOVIGILANCEAND THE MONITORING OFADVERSE DRUG REACTION Jibuti Sh., Chapichadze Z., Gongadze N., Gorgaslidze N. Ministry of Labour, Health and SocialAffairs of Georgia Legal Entity of Public LawState Regulation Agency for Medical Activities; Tbilisi State Medical University, The Department of Medical pharmacology and Pharmacotherapy, Georgia Pharmacovigilance principles and safe drug use promotion activity, recommended by WHO, are present in this article. Irrational drug use potential risks and its prevention are analyzed in the article. The authors stressed the importance of organization of adverse drug reaction monitoring system that includes: spontaneous adverse drug reaction reporting, analysis of computational material and evaluation of safety profile of the drugs, introduction of the receipt system, analysis of collected adverse drug reaction information in specific format and sending this information to Uppsala ADR monitoring international center. Additionally, the following aspects of pharmacovigilance are considered: drug post-marketing surveillance, risk/benefit ration analysis and ways of prevention the drug risks. 67

68 TARGETED DRUG DELIVERY SYSTEMS FOR ANTHELMINTIC SUBSTANCES OF BENZIMIDAZOLES 1 Khalikov S., 2 Dushkin A., 2 Chistyachenko Yu., 2 Evseenko V., 3 Arkhipov I. 1 A.N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences- 28, Vavilova str., Moscow , Russia; 2 Institute of Solid State Chemistry and Mechanochemistry - 18, Kutateladze str., Novosibirsk, , Russia; 3 K.I. Scriabin State Scientific Institute of Helminthology -28, Bolshaya Cheremushkinskaya str., Moscow , Russia Current treatments based on the use of a wide range of medicines. Many of the drugs used often do not provide the required treatment efficiency and, even worse, their use can cause unwanted side effects. Because of this, in the world of pharmacy and veterinary science is constantly developing new and improved drugs already in use. Helminthosis of animals distributed from arctic latitudes to the equator and dangerous that can infect both humans [1,2]. Helminthes infected more than a billion people. The number of patients infected with intestinal worms is the third largest in the world. According to WHO, the total number of illnesses and deaths from intestinal helminthes higher than from bacterial, viral infections and other parasitic diseases combined. In some cases, treatment of parasitic diseases not effectively and leads to severe consequences - deterioration of the immune system and the emergence of secondary immunodeficiency disorders homeostasis mechanisms, arrhythmia, mental disorders, the formation of tumors, including malignant. Therefore, prevention and treatment of helminthosis - one of the most urgent problems of modern medicine and veterinary medicine. The first time we have developed original products "medapec" and "medapol" by mechanochemical synthesis based on (1H-benzimidazol-2-yl)-carbamic acid methyl ester/active ingredient of anthelmint drug medamin /and polymers ( apple pectin and PMAA )[3]. Medapec shown high efficiency model lavral echinococcosis rats closest to the corresponding human pathology. Unlike medamin, medapec rapidly absorbed and had a high value of the angular distribution volume. Bioavailability study showed that medapec penetrated in larvotsisty alveolar echinococcosis, have a disastrous effect on the parasite germentative layer and at the same time did not accumulate in the organs and tissues of the host. The inclusion of pectin giving lower LD 50 up to 4000 mg/kg. It should be noted that most of the substances used in practice or bad drugs are virtually insoluble in water [4]. To change the water solubility of poorly soluble substances different methods are used: - Physical: A. Reducing the particle size (grinding of substance, obtaining nanosuspensions/nanocrystals) B. Modification of the crystal structure (polymorphic transformation). B. Preparation of dispersions with excipients (mixtures, solid dispersions, solid solutions). - Chemical: A. Changing the ph and the transfer of active ingredient (AI) in the ionized form. B. Education salt forms AI. C. Complexation of AI with various kind of substances. Described previously [3], the method of solid-phase mechanochemical modification of medamin substance can be assigned to one of the methods of complexation (item "C"). These works are further developed in [5-7]. Schematically, the process of conformity to solid complexes presented in these papers is as follows: the joint grinding of two components occurs at the first stage uniform mixing (A), with continued mechanical stress occurs aggregation finely dispersed particles (B). Continued grinding leads to molecular mixing of solid state components (B) and, depending on their nature occurs or the formation of complexes due to the forces hydrophobic interaction, adhesion forces, etc. As the object of investigation were chosen based of substance of benzimidazole anthelmintic drugs row - medamin and albendazole, as well as polymers - Arabinogalactan /AG/, Hydroxyethylstarch /HES/, PVP, MCC, pectin etc. The study of the formation of complexes during mechanochemical treatment of drug substances and polymers was carried out in various grinders - activators. On the basis of the integrated intensity of the peak with retention index was calculated water solubility of albendazole samples analyzed. Data analysis showed that: - all complexes possesses higher solubility than 68

69 themselves substance; - the quantity of water solubility depends on the nature of the polymers and the ratio substance: polymer. - Most-significant increase of aqueous solubility is observed in the case of complexes with arabinogalactan (AG). Apparently for these complexes and should expect a significant increase in anthelmintic activity, which was confirmed in the study [8]. Determination of dispersion was performed on a laser analyzer "SALD " (SALD Nanoparticle Size Analyzer) of "Shimadzu". The results showed that the complexes are highly dispersed system, due to the inclusion of fine particles of albendazole into the pores of the polymer. In addition, complexes of albendazole with AG and HES include nanoparticles, which should help to strengthen the anthelmintic action of these drugs. Nematocidic activity of albendazole complexes at laboratory model of trichinosis (T.spiralis) in white mice experimentally infested showed that the complexes based on polymers (PVP and AG) had 100% efficiency even with reduced rates of albendazole more 10 times. Albendazole complex with HES also possessed relatively high efficiency (97.5%) compared with the substance of albendazole (73%). Here we must also take into account that for content of a.i. of albendazole in the complexes is more than 10 times smaller. Therefore, albendazole complexes obtained polymers were less toxic expected, it was experimentally confirmed. Parameters acute drug toxicity (LD50) was determined by the method of [9] and it was found that the supramolecular complexes of albendazole with AG and PVP were less toxic (LD50=5000 mg/kg) than the base albendazole (LD50 = 2450 mg / kg). Test of cestodic activity of the same drugs as compared to albendazole was carried out on white mice experimentally infested H. nana. As a result, 100 % efficiency at mice showed by complex of albendazole:ag = 1:10. The drug proved to be active against both imaginal and immature cestodes. Albendazole complex with PVP slightly inferior in activity. Effectiveness of the drug was slightly more than 90 %, which is still higher than that for the complex albendazole with HES (24%) and for substance of albendazole ( 0%). Study on trematodic activity (F. hepatica) of albendazole complexes with polymers (AG and PVP) showed 95% efficiency, while the efficacy of albendazole was 45%.Thus we have shown the advantage of the complexes over the known substances both in efficiency and application doses. The results obtained allow us to speak about the benefits of alternative ways for creating of new anthelmintic drugs by mechanochemical modification of substances by polymers [5,6]: - Technology allows drugs with controlled solubility, bioavailability and pharmacological effect. - Derived drugs are highly effective at lower doses of substance, and so they are less toxic. - This technology allows the final product to acquire the beneficial properties of polysaccharides themselves. It was previously shown based on medapec the possibility to reduce the toxicity of the drug. The same advantages can be taken by using of AG because it has the wide spectrum of activity (immunomodulatory, prebiotic and others). So, new complexes based on substances of drugs and AG must be very prospective as well. - solid phase mechanochemical synthesis gives the possibilities to obtain "molecular" mixes of two components in the absence of solvent or liquid phase under intense mechanical working, allowing to obtain the supramolecular systems comprising compounds having no joint area of solubility, for example water-soluble polysaccharides and is practically insoluble in water drug substances. - Proposed technology is a simplified and cost-effective to produce new drugs, because excludes the processes of dissolution and heating of the starting components, the deposition and crystallization of the final product, no wastewater and multistep processes, etc. -This technology makes it possible to adjust the properties of drugs due to the proximity to the polysaccharide structures of biologically active centers of the body and obtain delivery vehicles-drug Delivery Systems. Until about the beginning of the 2000, the main innovative direction in pharmacy (so called Drug Discovery) was the creation of new active substances molecules. This process is to search and multiple trials of newly synthesized or chemically modified natural organic compounds. And on statistical tick of about 10,000 "starting" connections to industrial production comes only one molecule. Drug trials can last for many years, with an average of 9-12 years, and the cost of development, according to various estimates, may be from 0.3 to 2 (average 0.8) billion US $ [10]. Another area of innovation is to improve the pharmacological properties and safety already in use in the pharmaceutical active substances due to their directed transport in a given region of the organism a given region of 69

70 the body, organ or cells, as well as speed control, time and place of action of a drug in the body (so called Drug Delivery Systems). Here, the duration of the development and the cost is usually several times shorter and cheaper. However, and this way allows you to output in high-performance treatment medications. According to the above reasons, the share of economic development Drug Delivery Systems has recently become dominant. So worldwide sales of drugs in 2012, made by technology Drug Delivery, estimated at ~ >140 billion US $ [10], while the market of Drug Discovery is about ~ >40-56 billion US $. This is an important topical issue gets, respectively, and avalanche increase in the number of publications on the topic "nanotechnology and creation of DDS." It should be noted that the accelerated development of Drug Delivery developments particularly advantageous for countries with insufficient manufacturing their own drugs, but seeking to accelerate the development in this area. Combination of materials set forth in this paper favors the development of alternative ways of creating new drugs by modifying the existing and substances used in practice. REFERENCES 1. Shuvalova E.P. Infectious diseases. M.: Medicine; 2001: Methodical instructions. Diagnosis, treatment and prevention of helminthiasis and diseases caused by intestinal protozoa. M.: Medicine; 2004: Khalikov S.S., Pominova T.Yu., Pereverseva E.I., Khodjaeva M.A., Karimov A., Musaev U.N., Aripov Kh.N. Preparation and physicochemical properties of polymeric complexes benzimidazolyl-2-methyl carbamate and apple pectin. Chemistry of Natural Compounds 1995; 6: Takagi T., Ramachandran Ch., Bermejo M., Yamashita S., Yu L.X., Amidon G.L. A Provisional Biopharmaceutical Classification of the Top 200 Oral Drug Products in the United States, Great Britain, Spain, and Japan. MOLECULAR PHARMACEUTICS 2006; 3(6): Dushkin A.V., Meteleva E.S., Chiatyachenko Yu.S., Khalikov S.S. Mechanochemical Synthesis and properties of solid dispersions, forming water-soluble supramolecular systems. Fundamental research 2013; 1(3): Dushkin A.V., Suntcova L.P., Khalikov S.S. Mechanochemical technology to improve solubility of drug. Fundamental research 2013; 1(2): Khalikov S.S., Dushkin A.V., Khalikov M.S. et al. Mechanochemical modification of properties of anthelmintic preparations. Chemistry for Sustainable Development 2011; 19(6): Glamazdin I.I., Arkhipov I.A., Odoevskaya I.M., Khilyuta N.V., Khalikov S.S., Chistyachenko Yu.S., Dushkin A.V. Anthelmintic efficacy in lab of Drug Delivery System based on albendazole obtained by mechanochemical technology. Russian Parasitological Journal 2013; 3: Belenky M.L. Elements of quantitative assessment of pharmacological effect. Leningrad: Gosmedizdat; 1963: Recent Advances in Novel Drug Carrier Systems. Ed. by Ali Demir Sezer. Publisher: InTech, Chapters published; 500. STUDY OF SOME FACTORS INFLUENCING THE BEHAVIOR OF CONSUMERS OF PHARMACEUTICAL PRODUCTS Beglaryan M. Yrevan State Medical University after M.Heratsi, Department of Pharmaceutical Management, Yerevan, Armenia Socio-economic changes that took place in the RA significantly influenced the development of the pharmaceutical market by stimulating competition in pharmacy business. The increase of the number of drugstores created wider pharmacy choice for consumers [1]. That is why knowing the customer will help pharmacy personnel establish ongoing relationships, which, in turn, will help understand the level of customer satisfaction and decision making processes [2]. 70

71 In a pharmaceutical market, as in any other, the customer behavior must be viewed from the marketing point of view as the most appropriate method to describe the interaction of all involved parties [3,4,5]. This approach is based on identifying and analyzing consumers real-world behavioral patterns [6,7]. The objective of the study was to reveal consumers priorities when choosing drugs or other pharmacy medical products (GMS). Materials and methods. Final consumers of pharmaceutical products were surveyed using a questionnaire. It consisted of the two below-mentioned sections, which provided the necessary data about the situation in general and allowed further analysis of consumers behavior: 1. consumers behavioral characteristics when making decision to purchase drugs or other medical products, 2. social-demographic characteristics of consumers. The study was conducted through surveying the consumers of pharmacies throughout the Republic of Armenia by using questionnaires. To evaluate and to make a decision of purchasing of any article of merchandise, including pharmaceutical one is under the influence of consumer s individual psychological and social-demographicfeatures, as well as information of the acquired article. For this reason all the evaluating factors were divided into two groups: 1. the consuming evaluating factors, connected with the consumer s psychological and socialdemographiccharacteristics; 2. the commercial evaluating factors, connected with the article s functional characteristics (Table 1). We considered the influence of some measurable factors on the process of purchase decision making. Variables that are used most frequently when studying consumers behavior are those of socio-demographic dimension. That has two reasons: a) the socio-demographic characteristics compared to other variables can be measured more easily, b) the needs and preferences, as well as intensity of the use of pharmaceutical pruducts are associated with socio-demographic characteristics of the consumers. socio-demographic characteristics Table 1. A theoretical model of consumers behavior in the process of purchasing Factors, influencing onto the consumer s behavior The consuming measurable factors The commercial measurable factors psycho-graphical drug characteristics characteristics functional characteristics of drugs - age - education - gender - social status - income - other - motivation - consumer ethnocentrism - consumer hostility - authority - other - manufacturer country - manufacturer firm - provider - price - packaging - other - indications for use - contraindications - composition - drug interactions - pharmacological properties - other Results and their discussion. The study has revealed that most influential socio-demographic characteristics of the consumers were their age, education and income. As a discipline, psychographics studies the system values of an individual, attitudes toward lifestyle, motivation, psychological parameters and other dimensions [5]. The analysis of drugstore customers behavior shows that drugs or other medical products are purchased for own use in 46% of the cases, while 44% of the buyers made the purchase for their families or friends. So, approximately the half of pharmacy customers can be viewed as consumers, whereas the other half simply buyers. The severity of the problem of choosing drugs or other medical products is determined by the risk the consumers undergo, which is tightly connected with the level of uncertainty of health consequences of the drug 71

72 choice. One of the ways of risk reduction is a thorough search for information. The current study shows that prior to making a purchase consumers refer to a wide range of sources of information. For the majority of consumers (56%) the main source of information is the counseling by doctors and pharmacists (so called official sources). The least frequently referred source of information is commercials (delivered via television, radio and print press) (11%). Ethnocentrism (Greek ethnos = population, and Latin centrum = centre) is an attitude or a worldview of a group of people, which is characterized by valuing their own ethnicity, social belonging or cultural identity higher than those of others [6]. A highly ethnocentric consumer places goods of the domestic production over those of foreign manufacturers. Exploring manifestations of ethnocentrism has shown that up to 12% of customers preferred domestic products, for 39% of consumers the manufacturing country was not important. Finally, about 49% of respondents gave preference to drugs of foreign companies. So, in Armenia drug consumers are characterized by low level of ethnocentrism. Those consumers who prefer drugs of foreign producers, most often purchase products of Western European countries (55%). As far as Eastern European pharmaceutical products are concerned, they constituted 28% of cases. This proves the popular notion among the Armenian people that similar products of developed countries are comparably more reliable in terms of quality and efficacy. Nevertheless, decision making process involved in purchasing a pharmaceutical product is not always lined up with the company or country origin of the product, but is predominantly determined by the price of the product. If a drug of local production is twice as cheap as its foreign counterpart, consumers 57% will purchase the local product, whereas only 35% will prefer foreign drugs. As to the study results, when purchasing expensive drugs, customers are mainly motivated by the manufacturer company and country (Fig. 1) more expencive, higher rating country more expensive higher rating company Fig. 1. Drug Choice Based on Country's and Company's Rating Almost half of the number of the consumers are ready to pay a higher price for company s or country s rating. Some investigators suggest that valuing a foreign manufacturing product could play no role in purchasing decision process if a particular consumer is hostile toward the country of origin of that product. In this case, consumer s attitudes toward that particular country annuls the obvious advantages of the product over its counterparts. Factors involved in commercial estimation of products can be divided into two groups: - valuation factors, associated with drugs functional characteristics, - valuation factors, associated with characteristics attributed to drugs. 72

73 Drugs functional characteristics are connected with their usefulness (drugs composition, indications for use, contraindications, ways of usage, interaction with other drugs). Characteristics attributed to drugs are not connected with therapeutic effectiveness, but have impact on the choice of drug (country and company, distributor, price, packaging, etc.). When choosing a pharmaceutical product, consumers try to get all the available information about functional and attributed characteristics of that product. According to the study results, consumers are most interested in the following functional characteristics of pharmaceutical products: indications for use (22%), way of usage (16%), contraindications (16%) (Fig. 2). storage conditions drug composition contraindications indications 0% 5% 10% 15% 20% 25% Fig. 2. Functional characteristics of drugs that consumers are interested in When trying to get all the available information about two products in order to make a further comparison, consumers tend to value functional characteristics the highest. Since drugs considered special products, i.e. their essential characteristics are associated with their therapeutic effect, consumers tend to overlook their functional characteristics and are basically ignorant of them. That is why factors attributable to drugs tend to be the most determining buying decision process. 0,35 0,3 0,25 0,2 0,15 0,1 0,05 0 Drug price Country of origin Producing Company Packaging Distributing Company Fig. 3. The significance of some drug characteristics in their choice by consumers The study of the consumer behavior conducted in pharmacies of the RA reveals that the main characteristics attributable to drugs are the price (32% of consumers), drug manufacturing country and company (23% and 20%, respectively) (Chart 3.). The majority of consumers believe that the quality of a drug depends on the country of its origin (79%) and company (82%). Conclusion Based on the above-mentioned, the assessment of pharmaceutical products and the process of purchase decision making by consumers is very complex, which is influenced by a group of factors related both to the drug (GMS) and to the consumers personality. An ongoing monitoring and analysis will enable the pharmacy s administration to maximize their profit, improve pharmaceutical care, raising it to a higher level and provide the population with pharmaceutical products of higher quality, safety, efficacy and affordability. 73

74 REFERENCES 1. Бишарян А.К. Ситуационное моделирование системы лекарственного снабжения в Республике Армения. Автореф. дисс д-ра фарм. наук. М.: 2001; Kotler Ph., Trias de Bes F. Lateral Marketing: A New Approach to Finding Product, Market, and Marketing Mix Ideas, John Wiley & Sons: 2003; Крылова Г.Д., Соколова М.И. Маркетинг. Теория и 86 ситуаций. М.: Изд.ЮНИТИ-ДАНА; 1999: Маркетинговые отношения "продавец-покупатель". Экономический вестник фармации 2003; 6: Новиков А.С. Анализ потребностей. Экономический вестник фармации. 2004; 3: Большой психологический словарь. Под редакцией Б. Г. Мещерякова, В. П. Зинченко М.: Изд.: Прайм-Еврознак; 2009; Stewart D.W., Zinkhan G.M. Enhancing Marketing Theory in Academic Research. Journal of the Academy of Marketing Science. 2006; 34: Гантер Б., Фернхам А. Типы потребителей: введение в психографику. Питер: 2001; 304. THE RESEARCH OF CHEMICAL STRUCTURE AND ANTIMICROBIAL ACTIVITY OF ARMENIAN APRICOT GUMS (GUMMI ARMENIACAE) 1 Chichoyan N., 2 Shekoyan V., 3 Mamyan S., 4 Galstyan H. Yerevan State Medical University after M. Heratsi, 1 Department of Pharmacognosy, 2 Department of Medical microbiology, 3 Molecule structure research center NAS RA, Institution of the scientific technological centre of organic and pharmaceutical chemistry of NAS RA, 0014 RA; 4 Institute of Hydroponic problem NAS RA (Armenia), Yerevan, 0082 Polysaccharides have important role in the plants, animals and human metabolism. Plant polysaccharides and their modified derivatives are widely used in medicine. Cellulose, hemicellulose, starch, inulin, gum, mucosa and pectin substances are related to the natural plantar polysaccharides or phytopolysaccharides [1]. Actually, there are some investigations related to different gums of plantar origin, particularly, the Acacia gum (Acacia senegal L., Acacia seyal L.), Guar gum (Cyamopsis tetragonoloba), Prosopis gum (Prosopis spp.) and other gums phytochemical research [2-4]. In this point of view the most urgent are the plantar polysaccharides of Armenia s flora considering an increased interest to the local sources all over the world, so it is becoming an issue of great importance. Nowadays, it is of crucial importance to study the structural peculiarities and the conditioned biological activity of the Gummi Armenicae of native origin as an alternative for the Gummi Arabicae, known as for its significance as effective emulsifier, stabilizer and dietary fiber in medicine and food industry [5-7]. At present gums are of great attention due to their antibacterial activity representing bactericide influence thereby acidic damage of microbial cell surface structures and suppression of intestinal flora [8,9]. Thus, the goal of our work became to separate and study the polysaccharide complex from the Apricot gum followed by its chemical content and antimicrobial activity investigation. Materials and methods. Plant materials The research was carried out in the Department of Pharmacognosy in YSMU and in the laboratory of <<Molecule Structure Research Center NAS RA>>, Institution of the <<Scientific Technological Centre of Organic and Pharmaceutical Chemistry of NAS RA>>. 74

75 The research material was the Apricot trees gum cultivated from different regions of Armenia within May-June Microbiological research was done at the Department of Microbiology and Virology of YSMU. The Analysis of polysaccharide fraction In order to reveal the chemical composition, the collected and dried gums were hydrolized with the help of sulphuric acid (1:50) 2M from 30 minutes to 24 hours (the hydrolysis was supervised by chromatography). The hydrolizate was neutralized, sedimented and refiltered. The ratio of filtered monosaccharides (1:3) was detected with the help of 95% alcohol. The quantity of polysaccharides in gums was determined by the method of gravimetric balance after drying. After the acid monosachharides (uronic acids) filtration the filtrates were evaporated till the dry residue and then dissolved in 70% alcohol to be used in chromatography of the neutral monosaccharides [10]. The refined layer of chromatography was used to establish the fraction composition quality (structure) of polysaccharide complex. Silicagel tins were performed for chromatography (SIL G/UV 254). The chromatography was made in benzene-methanol-acetic solvent system (1:3:1). The standard control materials were xylose, arabinose, glucose and galacstose. The quantitative ratio of monosaccharides in the examined polysaccharide complex was detected by the method of MRI after the monosaccharides separation according to the anilinphtalate reactivity. The amount of acid monosaccharide was determined by carbazole with colorizing reaction in the acidic medium [11,12]. Spectral Analysis The ranges of a nuclear magnetic resonance 1 H and 13 C took out on the Varian-Mercury device 300VX (300 MHz) in D2O solution (99,9%) at 30 C (the internal standard an acetone; δh 2,225 m of, δc m ). Antimicrobial susceptibility testing The examine antimicrobial activity of the Apricot gum to Staphylococcus aureus 1, Staphylococcus aureus 209, Shigella flexneri 6858, Escherichia coli 0-55, Candida albicans, water solution of Apricot gum was prepared and the following dilutions were performed: 1:5, 1:10, 1:50, 1:80, 1: ml of physiological solution was added to the fresh pure cultures of the above mentioned microbes and homogenous microbial suspensions were prepared and uniformly inoculated onto the surface of a nutricional agar medium. Then the drops of different dilutions of Apricot gum are carefully placed on the agar surface. During incubation microorganisms multiplied forming a visible haze of cells. Clear areas, indicating lack of growth were detected, which were measured in milimeters. The test relies on the same principle as the Kirby-Bauer disc diffusion method. To cultivate Staphylococcus aureus the yolk-salt agar was used; for Escherichia coli Endo media; for Candida albicans Sabouraud s media were used [13]. Results and discussion Chemical structure of polysaccharide fraction Results of the study have shown that the Apricot gums cultivated from different regions of Armenia, serving as a material for separation of the polysaccharide complex predominantly consisted of the uronic acids and the neutral monosaccharides. Values of indices of the uronic acids and of the neutral monosaccharides were recorded for the collected samples. Generally, uronic acids in all the samples in mean values were 84,32±0,45% versus the neutral monosaccharides presented as 15,69± 0,2% in mean. The highest content of uronic acids was revealed in the Apricot gums polysaccharide complex harvested from in Eghegnadzor (Chiva) 92.43±0.44%, the highest content of the neutral monosaccharides (almost equal amount) was recorded in Arzni 16,53±0.24% and 16.77±0.34% in Tandzut. Results are given in the table below. According to literary data, the uronic acids are widespread in nature and their significant amount in the Apricot gum s total polysaccharides content, probably, predetermines its therapeutic antimicrobial and anti-inflammatory activities. Particularly, the D-glucouronic acid is the most common composite in polysaccharide-containing plants (gums, hemicelluloses) [10]. 75

76 Therefore, their finding in great amounts in the polysaccharide complex will serve as a basis in the further studies on Apricot gums, considering its antimicrobial anti-inflammatory effect. Based on the native Apricot gums hydrolysis products the following neutral monosaccharides, such as galactosе, arabinosе, xilosе and glucose have been revealed in the polysaccharide complex. Thus, the polysaccharide complex separation from the gums harvested from the Apricot trees of different regions of Armenia was performed and the qualitative and quantitative contents were detected. By means of the chromatographic methods of investigation the presence of galactose, arabinose, xylose, glucose and the uronic acids in the Apricot gums hydrolysate was determined. Predominating components in the studied samples were the uronic acids in the Apricot gum polysaccharide complex assuming their antimicrobial properties. Spectral Analysis The chemical shifts of pyranosyl monosaccharides were also detected in the laboratory of the <<Molecule Structure Research Center NAS RA>> Institute of the <<Scientific Technological Centre of Organic and Pharmaceutical Chemistry of NAS RA>>. The ranges of a nuclear magnetic resonance 1 H and 13 C took out on the Varian-Mercury device 300VX (300 MHz) in D2O solution (99,9%) at 30 C (the internal standard an acetone; δh 2,225 m of, δc m of). The first sample of mixture contained approximately: 35% β-l-arabinopyranoses and 65% α-l- arabinopyranoses (H1- β5.22, d, 3J 3,5Hz, H1-α 4.50, d, 3J 7,8Hz, H2-α 3.50, dd, 3J 7,8Hz, 3J 9,8Hz, , m, 9 H; C1-α 97.9, C2- α 73.0, C3-α 73.6, C4-α 69.6, C5-α 67.5, C1-β 93.7,C2- β 69.6, C3- β 69.8, C4- β 69.8, C5- β 63.6). The second sample of mixture was approximately of: 50% α-d-galactopyranoses and 50% β-d-galactopyranoses (H1-α5.27, d, 3J 3,5Hz, H1-β4.59, d, 3J 7,8Hz, H2-β3.49, dd, 3J 7,8Hz, 3J 9,9Hz, , m, 11H; C1-α 93.6, C2-α 69.7, C3-α 70.5, C4-α 70.6, C5-α 71.8, C6-α 62.5, C1-β 97.8, C2-β 73.2, C3-β 74.1, C4-β 70.1, C5-β 76.5, C6-β 62.3). The third sample of mixture was approximately of: 70% α-d-glucopyranoses and 30% β-d-glucopyranoses (H1-α 5.23, d, 3J 3,7Hz, H1-β 4.64, d, 3J 7,9Hz, H2-β3.24, dd, 3J 7,9Hz, 3J 9,3Hz, , m, 4 H, , m, 7H; C1-α 92.7, C2-α 72.1, C3-α 73.4, C4-α 70.6, C5-α 72.1, C6-α 61.2, C1-β 96.5, C2-β74.8, C3-β 76.4, C4-β 70.2, C5-β 76.6, C6-β 61.4). From the 1 H and 13 C nuclear magnetic resonance analysis the following ranges of polysaccharide complex fractions consisting of the remnants of β-l-arabinopyranoses and α-l-arabinopyranoses, α-d-galactopyranoses and β-dgalactopyranoses, α-d-glucopyranoses and β-d-glucopyranoses were detected Study on the Armenian Apricot gums antibacterial activity The results revealed that the bacteria in the loop plates were without expanded regions in diameter, expressed in millimeters (d-mm). The antimicrobial activity of Apricot gum was compared with the same activity of Furazolidonum. The obtained data regarding 24-hour exposure are represented in the table after. Correlation of the data observed with the corresponding antibacterial properties: d=8 mm 13 mm low antibacterial activity d=14 mm 19 mm moderate antibacterial activity d=20 mm 25 mm high antibacterial activity It became clear that the Apricot gum s water solutions (1:5, 1:10, 1:50, 1:80, 1:500 in dilutions) had low antimicribial activity for Staphylococcus aureus 209, expressing the zone of inhibition of 8 mm in all the dilutions. In case of Staphylococcus aureus 1; it was from low to moderate activity, having d=8mm in 1:5, 1:10, 1:50, 1:80 dilutions, but d=16 mm in case of 1:500 dilution. So, the greater is dilution the higher is the antimicrobial activity provided. 76

77 The same tendency was revealed in plates with Sh. flexneri 6858 and E. coli 0-55, which was expressed from low to moderate activity of acting substance. This may be explained by discrease in viscosity in the highest dilution. Apricot gum had also antimicrobial activity to C. albicans. In the whole dilutions it suppresses the growth by the same way, exhibiting the same clear zone of inhibition. Conclusion Thus, in result of the investigation performed we conclude: - By chromatographic method of investigation the presence of some polysaccharides, such as galactose, arabinose, xylose, glucose and uronic acids in the gums hydrolysate was revealed. - By the method of spectral analysis (PМR 1 Н and NMR 13 C) the structure of apricot gums polysaccharide fraction was detected. - The research results confirmed an antibacterial activity of the Apricot gums. - Antimicrobial activity of Apricot gum to microorganisms was directly proportional to the degree of dilutions. It was revealed that Apricot gums water solutions have from low to moderate antibacterial activity in dilutiondependent manner regarding to Staphylococcus aureus 1, E. coli, and Sh. flexneri 6858, which may be explained by descrease in viscosity of acting substance. - The highest dilution of Apricot gum showed the highest antibacterial activity Escherichia coli 0-55 gram in relation to the negative bacteria. The results obtained will be followed by more deep investigations and will stimulate application of the gums of local origin in the medico-pharmacological aspect. REFERENCES 1. Babeshina L.G., Gorina Ya.V., Kolokolava A.P, Krasnov Е.А., Karpov M.R. The study on some types of polysaccharide sorts Sphagnum L. Journal of Siberian Federal University. Chemistry 2010; 4: Yolanda L.López-Franco, Córdova-Moreno Raúl E., Francisco M. Goycoolea, Miguel A. Valdez, Josue Juárez- Onofre, Jaime Lizardi-Mendoza Elmanan Mona, Saphwan Al-Assaf, Phillips Glyn.O., Williams Peter.A. Studies on Acacia exudate gums: Part VI. Interfacial rheology of Acacia senegal and Acacia seyal. Food Hydrocolloids 2008; 22: Verbecen D., Dierckx S., Dewettinck K. Exudate gums: occurrence, production, and applications. Appl.Microbiol. Biotechnol. 2003; 63: Chichoyan N. Natural raw material resources of apricot gums of republic Armenia and perspectives of their use. Actual problems of Botany in Armenia. Materials of international conference. Inst. of Botany NAS RA. Press.Yerevan; Chichoyan N. Pharmacognostic studies of gums collected from apricot trees growing in 8.Armenia and perspectives of their use. Georgian Medical News 2009; 1: Chichoyan N. Gummi Armeniacae collected from Apricot trees in Armenia- perspective source of arabinigalactan. Georgian Medical News 2011; 3: Torquato D.S., Ferreira M.L., Brito G.C. Sá.E.S., Pinto G.A.S., Azevedo E.H.F. Evaluation of Antimicrobial Activity of Cashew Tree Gum. World Journal of Microbiology and Biotechnology 2004; 20: Bhawna Sunil Negi, Bharti P. Dave In vitro Antimicrobial Activity of Acacia catechu and Its Phytochemical Analysis. Indian J Microbiol. 2010; 50: Soboleva V.A., Chushenko V.N., Kolomiyets A.A., Dankevich O.S. Isolation of polysaccharides horse chestnut and study of its chemical composition Zaitseva GN, Afanas'eva TP. Descending paper filter chromatography in quantitative determination of carbohydrates. Biokhim. 1957; 22: Zhdanov YuA, Dorofeenko TN, Korolchenko TA. Workshop in carbohydrate chemistry (monosaccharides). press:m.: High. School Birger M.O. The directory on microbiological and virologic methods of research. Medicine. Press; M

78 THE SEARCH OF NEW HERBAL ANTICONVULSANTS Prokopenko Yu., Georgiyants V., Tsyvunin V., Mischenko V., Blyznyuk N., Golovchenko O. National University of Pharmacy, Kharkov, Ukraine Epilepsy was one of the first described brain disorders. Firstly it was mentioned more than 3000 years ago, when the early physician Hippocrates suggested that epilepsy was a disorder of the brain. Now it is known that epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiological, cognitive, psychological, and social consequences. Almost 50 million people in the world have experienced an unprovoked seizure and been diagnosed with epilepsy. About 80 percent of those diagnosed with epilepsy can control seizures with modern medicines and surgical techniques. However, about 25 to 30 percent of people with epilepsy will continue to experience seizures even with the best available treatment. Despite the availability of a wide range of antiepileptic medicines a problem of the search for new drugs with anticonvulsant properties among the herbal medicinal products remains acute. It is well known that herbal remedies take a leading position due to their mild assimilation by the human body, application performance, breadth of therapeutic action, along with a minimal risk of side effects, especially during long-term treatment of chronic diseases, which include epilepsy. In addition, herbal medicines usually have a complex influence on the disease pathogenesis. But the problem is that currently pharmaceutical markets of Ukraine and other countries of the world have practically no facilities for treatment of epilepsy by herbal remedies. Literature sources have shown that members of different plant families can provide an anticonvunsant activity. According to the literature data, research of anticonvulsant activity has been carried out. Results of research have distinguished several herbs with pronounced anticonvulsant activity, e. g. members of Fumariaceae family. This family comprises Fumaria schleicheri Soy-Willem, which is a weed plant widespread in Ukraine. Previously studies of chemical compound, pharmacological activity and toxicity of Fumaria schleicheri has been carried out. It was found that chemical composition of Fumaria schleicheri was presented by isoquinoline alkaloids, flavonoids, terpenoids, polysaccharides, etc. Different groups of compounds were isolated from the Fumaria schleicheri Soy-Willem herb by conventional methods. The main alkaloid protopine was isolated from the sum of isoquinoline alkaloids of Fumaria schleicheri herb. On the model of pentylenetetrazole-induced seizures the dry extract of Fumaria schleicheri has shown a potent anticonvulsant activity which resulted in the significant increase in the latency period of the appearance of the first seizures and reducing the duration of the convulsive period in the group. The dry extract of Fumaria chleicheri in experimental dose has had a pronounced anti-seizure effect by the reduction of quantity of mice with clonic and tonic convulsions and the lethality decreasing in the group compared with the control animals. Isoquinoline alkaloid protopine statistically reliably raised the latency period compared with the control group. This effect is dose-dependent that is confirmed by the absence of reliable differences between time indicators in control group and group of animals which received protopine at the higher dose. The increase in the latency period while taking the flavonoid fraction did not reach the level of statistical significance. Other compounds did not have an influence on time indicators of the experimental seizures. Furthermore, studies have shown on the model of closed traumatic brain injury in rats that dry extracts of Fumaria schleicheri had a neuroprotective effect by the reduction of behavioral and cognitive disorders, normalization of the brain mass/body weight ratio and the prooxidative-antioxidative balance in central nervous system. According to the stated results the expressed anticonvulsant properties of the dry extract of Fumaria schleicheri have been determined. Results will be used in our further work in developing of new herbal anticonvulsant. 78

79 VINCA HERBACEA-S WALDST. ET KIT. leikopoezis mastimulirebeli indolis alkaloidebis analizi vacnaze v., CxikvaZe g., mujiri m., kinwurasvili l., sulaze T., vacnaze n., gagua n., moiswrafisvili m., gogitize n., muskiasvili n. Tbilisis saxelmwifo samedicino universiteti, i. qutatelazis farmakoqimiis instituti, Tbilisi, saqartvelo gasuli saukunis 60-ian wlebsi institutis qimiis da analizis ganyofilebasi (drevandel alkaloidebis laboratoriasi) prof. q. mujiris da farm. mecn. kandidatis T.beJaniSvilis mier dawyebuli iyo kvlevebi saqartvelosi fartod gavrcelebul mcenareze Vinca herbacea (balaxovani gvelis suro), rogorc citotoqsiuri moqmedebis preparatis Sesaqmnel wyaroze [2,4]. Semdgom wlebsi, mcenaris miwisqveda nawilebidan, kvlevis Sedegad mirebuli iyo substancia (pirobitad leikobetinad wodebuli), romelsac axasaiatebda mkvetrad gamoxatuli leikopoezis mastimulirebeli aqtioba. farmakologiur kvlevebs xelmzrvanelobda medicinis mecn. doqtori, prof. m. gedevanisvili. am kvlevebis Tanamonawile wlebis manzilze iyvnen aw gardacvlili farm. mecn. kandidati d. jayeli da medicinis mecn. kandidati i. sixarulize [2,6]. leikobetini, leikocitebis ardgenaze periferiul sisxlsi stabilur da kargad gamoxatul dadebit zemoqmedebis unars avlens mielotoqsikuri preparatebit an maionizirebeli dasxivebit damusavebul cxovelebsi. modelur transplantologiur eqsperimentsi am alkaloidebis jamis zemoqmedebam mnisvnelovnad gazarda endogenuri granulocituri koloniebis ricxvi ac-membranebze (acetilcelulozuri-membranebi) da leikocitebis raodenoba periferiul sisxlsi (110%-ze meti). leikobetinis moqmedebis meqanizmi alfa-adrenergul komponents Seicavs, rac farmakologiuri sasualebebit aris dadgenili. leikobetini, rogorc hemopoezuri, kerzod, granulocituri ujredebis stimulatori - rekomendebulia, rogorc rekombinatur G-CSF-Tan (granulocituri koloniebis mastimulirebeli faqtori) ertdrouli an Tanmimdevruli gamoyenebis rejimebsi mielosupresoruli qimioterapiis pirobebsi polipotenturi an winamorbedi ujredebis (PBSC/PBPC) efeqturi mobilizaciisa da periferiuli sisxlidan mati optimaluri gamosvlis TvalsazrisiTac Zvlis tvinis gadanergvis dros. samkurnalo nedleulis gvelis suros fesvebis da fesurebis, leikobetinis substanciis standartizaciebistvis SemuSavebuli iyo satanado analizuri metodikebi [3]. leikobetinis substanciasi Semavali farmakologiurad aqtiuri alkaloidebia: 79

80 tabersonini rezerpini N H 3 CO N H H N H CH 3 N H H H 3 COOC O COOCH 3 maidini kopsinini N N H H H 3 CO OCH 3 N H O H H 3 COOC O CH 3 N H psevdokopsinini COOCH 3 11-meToqsitabersonini N N H 3 C N H COOCH 3 H 3 CO N H norfluorokurarini COOCH 3 H 21 N H 16 CHO farmakologiuri kvlevebit dadgenilia, rom balaxovani gvelis surodan oqsindoluri alkaloidi maidini da misi stereo izomeri izomaidini garda leikopoezis stimulaciisa, xasiatdebian antioqsidanturi da antiradikaluri aqtiurobit, amastan astimulireben apoptozs aramitoqondriuli gzit [1]. leikobetinis substanciasi tabersoninis, rezerpininis, maidinis, norfluorokurarinis, kopsininis raodenobiti gansazrvris qromatospeqtrofotometruli metodika: 0,5g (zusti wona) leikobetinis substancias xsnian qloroform-metanolis (8/2 v/v) narevis 5-ml-Si, gadaaqvt 10ml. moculobis gamzom kolbsi da imave narevit Seavseben nisnulamde (xsnari A). A xsnaris TiTo mililitri gadaaqvt Txelfenovani qromatografiuli firfitis (18x23sm, sorbenti silikageli LS 5/40µ) sastarto xazze. igive firfitaze gverdit SeaqvT saanalizo alkaloidis sarwmuno nimusis xsnari 5 80

81 mkg/0,1ml raodenobit. Txel fenaze qromatografireba tabersoninis, rezerpininis da maidinistvis tardeboda sistemasi benzoli-metanoli (9:1), xolo norfluorokurarinisa da kopsininistvis benzoli-etilacetati-metanoli (2:3:1). sarwmuno nimusis doneze lokalizebul zonas amoireben, alkaloidis eluirebas axdenen etilis spirtit, gamxsnels amoaqroleben, nasts xsnian 2ml etilis spirtsi ganzavebis koeficientis Sesabamisad (xsnari B). mirebuli ganzavebuli xsnarebis optikur simkvrives (D) sazrvraven speqtrofotometrze: tabersoninis nm, rezerpininis nm, maidinis nm, norfluorokurarinis nm, kopsininis nm. Sesadarebel standartad iyeneben etilis spirts. ganzavebis koeficientebia: maidinistvis 1:1000; rezerpininis, norfluorokurarinis da kopsininistvis 1:250; tabersoninistvis 1:100. leikobetinis substanciasi calkeuli alkaloidis procentuli Semcveloba gamoitvleba formulit: xx = D V 1 V 3 V E 1% 1სმ m VV 2 VV 4 (100 WW) % sadac: D sacdeli xsnaris optikuri simkvrive; EE 1% 1სმ saanalizo alkaloidis standartuli nimusis etanoliani xsnaris STanTqmis xvedriti macvenebeli: tabersoninis, rezerpininis, maidinis, norfluorokurarinis, kopsininis 98.8, 185.7, 737.1, da Sesabamisad; m leikobetinis wonaki (g); V 1 A xsnaris moculoba (ml); V 2 firfitaze Setanili A xsnaris moculoba (ml); V 3 B xsnaris moculoba (ml); V 4 gasazaveblad arebuli B xsnaris moculoba (ml); V 5 gazavebuli B xsnaris moculoba (ml); W Srobisas masis danakargi (%). ertdroulad SemuSavda leikobetinis substanciasi dominanti farmakologiurad aqtiuri alkaloidis maidinis Tvisobrivi da raodenobrivi Sefasebis metodika maralefeqturi qromatografiis metodis gamoyenebit Agilent 1100 danadgarze, sveti: Simmetry C-18, (250mm 4,6mm, 5µm, Waters), izokratuli mobiluri faza fosfatis buferi (ph=3), acetonitrili (8/2 v/v), gamosvlis dro 1 ml/wt. injeqtireba 20 mkl., DAD-226nm. saanalizo xsnari: 10mg. leikobetinis substancia gaxsnili 100 ml. mobilur fazasi [5]. maralefeqturi sitxuri qromatografis injeqtorsi cal-calke vaxdendit mkl standartuli da sakvlevi xsnarebis inicirebas. sakvlev nimussi maidinis raodenobas vitvlidit Semdegi formulit:^^ TT = A maj +0, AA EEEE 1, mm EEEE 100 mm eeeeee gantolebis mixedvit Y= ax+b Cvens SemTxvevaSi Y=1, , AA mmmmmm maidinis pikis fartobi; AA EEEE Sida standartis pikis fartobi; mm EEEE maidinis koncentracia; mm eeeeee Sida standartis koncentracia. 81

82 SemoTavazebuli metodis validaciam gvicvena, rom metodika warmoebadi, zusti da swrafia da gvazlevs maidinis gansazrvris sasualebas sxva alkaloidebis arsebobisas. dadgenilia, rom mcenareuli nedleuli unda Segrovdes yvavilobis da nayofmsxmoiarobis fazasi: leikobetinis gamosavali meryeobs 1,15-1,40% farglebsi, maidinis raodenoba leikobetinsi Seadgens 18,4-19,6%. Catarebulia winaklinikuri kvlevebi leikobetinze, rogorc leikopoezis mastimulirebel sasualebaze, SemuSavebulia da Sedgenilia dfs Vinca herbacea-s fesvebze da fesurebze, leikobetinis samkurnalo formaze kafsulebis saxit. literatura 1. n. gagua. mcenareuli alkaloidebis Semcveli wamalt formebis mirebis Tanamedrove teqnologiebis SemuSaveba. dis. doqtoris akademiuri xarisxis mosapoveblad farmaciasi. Tb.: 2012; Джакели Э.З., Сихарулидзе И.С., Моисцрапишвили М.М., Гедеванишвили М.Д. Алкалоиды корней Vinca herbacea W. et K. и их биологическая активность. Международный конгресс фармацевтов Грузии. Тб.: 2002; Джакели Э.З., Вачнадзе В.Ю. Хроматоспектрофотометрический метод количественного определения биологически активных алкалоидов Vinca herbacea W. et K. Georgia Chemiccal News 2002;10: Муджири К.С., Бежанишвили Т.С., Джакели Э.З., Киквидзе И.М. Исследование методов распределительной хроматографии для разделения суммы алкалоидов Vinca herbacea W. et K. IX международный съезд по общей и прикладной химии. М.: Наука; 1965: Gagua N., Baghdikian B., Mabzouki F., Elias R., Vachnadze V., Bakuridze A., Ollivier E. HPLC determination of maydine in Vinca Herbaceae. Natural Products Communications 2011;6: Mertins O., Chana K.I., Job K. Medicinal plants with potential anticancer aqtivities. International Journal of Pharmacy. Tech. Research. 2012; SUMMARY ANALYSIS OF INDOLIC ALKALOIDS FROM VINCA HERBACEA W. ET K. STIMULATORS OF LEUCOPOIESIS Vachnadze V., Chikvadze G., Mujiri M., Kintsurahvili L., Suladze T., Vachnadze N., Gagua N., Moistsrapishvili M., Gogitidze N., Mushkiashvili N. Tbilisi State Medical University, Kutateladze Institute of Pharmakochemistry, Georgia Based on the results of pharmacological studies it has been established that Leikobetine crude indolic alkaloids stimulates leucopoiesis and alcaloid majdin exhibit antioxidant, antiradical aqtivity and stimulate apoptosis through non micochondrial ways. The reproducible technique of qualitative and quantitative determination of majdine, reserpinine, tabersonine, copsinine, pseudocopsinine, 11-metoxytabersonine, norfluorokurarine of chromatospeqtrophotometry, and of majdine high-performance liquid chromatography in the total medication- Leikobetine from different vegetative organs of Vinca herbacea and pharmacologically active alkaloids. The provided methods can be used for standartization of vegetative row material and phytopreparations created on its basis. 82

83 olanzapinis gansazrvra adamianis sisxlsi sitxur qromatografiuli mas speqtrometruli (LC/MS/MS) metodit 1 murtazasvili T., 1 maxaraze r., 1 sivsivaze k., 1 imnaze n., 2 joxaze m., 2 TuSuraSvili p. 1 Tbilisis saxelmwifo samedicino universitetis farmacevtuli da toqsikologiuri qimiis departamenti; 2 ssip levan samxaraulis sasamartlo eqspertizis erovnuli biuros qimiur-narkologiuri departamenti, saqartvelo Sizofrenia warmoadgens ZiriTad fsiqiatriul daavadebas, romelsac axasiatebs azrovnebisa da arqmis Zireuli darrvevebi, Seusabamo emociuri reagirebita da/an emociuri sferos gasadavebit. qimiur-toqsikologiuri TvalsazrisiT, gansakutrebul interess iwvevs meore Taobis antifsiqozuri sasualebebi, kerzod risperidoni, olanzapini da klozapini, romlebic aseve cnobilia atipiuri anatifsiqozuri preparatebis saxelwodebit. arnisnuli samkurnalo sasualebebi Setanilia Sizofreniis da sxva fsiqozuri aslilobebis klinikuri mdgomareobis martvis saxelmwifo standartsi, aseve saertasoriso gaidlainebsi da Sesabamisad aqtiurad inisneba msoflios da mat Soris saqartvelos klinikebsi Sizofreniis sxadasxva stadiis samkurnalod [2,4]. olanzapini (nax. 1) aris antifsiqozuri sasualeba, romelsac axasiatebs naklebad gamoxatuli, mkurnalobastan dakavsirebuli, eqstrapiramiduli simptomebi da efeqturad amcirebs saerto fsiqopatologiur surats. arnisnulidan gamomdinare preparati, sxva antifsiqozur sasualebebtan SedarebiT, ufro xsirad inisneba Sesabamisi jgufis pacientebsi [2]. olanzapini aris susti fuze xasiatis mqone nivtiereba, misi pka meryeobs farglebsi [3]. preparats ireben Semdegi dozit: mg/dresi da plazmasi koncentracia meryeobs mg/l [3,4]. nax. 1. olanzapini gamoqveynebulia rigi samecniero statiebi, sadac arwerilia olanzapinis gansazrvris metodi sxvadasxva biologiur masalasi. am moxsenebebsi arwerilia gazuri qromatografiuli analizis metodi azotfosforul deteqtortan kombinaciasi (GC NPD) [5,6] da maralefeqturi sitxuri qromatografia ultraiisferi, fluorescentuli da eleqtroqimiuri deteqtirebit, obieqtis derivatizaciis Semdeg [7-10]. ukanasknel wlebsi sitxuri qromatografiis tandemma mas speqtrometriastan (LC MS/MS) daamtkica, rom is aris mzlavri iarari, udidesi sizustit adgens preparatebis, Tu sxva toqsikuri nivtierebebis minorul raodenobebs sxvadasxva biologiur obieqtebsi. sainteresoa publikaciebi, sadac arwerilia LC/MS/MS metodis gamoyeneba adamianis plazmasi da Tavis tvinsi olanzapinis raodenobrivi analizis miznit [11-18]. 83

84 arnisnulidan gamomdinare aqtualurad migvacnia axali modificirebuli LC/MS/MS metodis gamoyeneba sisxlsi olanzapinis gansazrvris miznit. olanzapinis cilebtan SekavSirebis procenti aris marali [3], amdenad ufro efeqturia olanzapinis izolireba mtlianad sisxlidan. didi raodenobit toqsikuri eqstrahentebis gamoyenebis Tavidan acilebis miznit, Cvens mier SerCeuli iyo olanzapinis izolireba cilebis daleqvis metodit. winamdebare statiasi arwerilia olanzapinis adaminis sisxlsi gansazrvris martivi, arwarmoebadi da marali mgrznobelobis kvlevis LC/MS/MS metodi, cilebis daleqvit izolirebis teqnologiis gamoyenebit. eqsperimentuli nawili olanzapinis substanciis SeZena moxda SIGMA-ALDRICH katalogit, gamoyenebuli organuli gamxsnelebi iyo maralefeqturi sitxuri qromatografiistvis gankutvnili sisuftavis (Merck). kvlevis miznit momzadebuli iyo 1.00 mg/ml koncentraciis deda xsnari metanolsi, romelic inaxeboda 2-8 C temperaturaze. am xsnaris ganzavebit xdeboda standartuli xsnarebis mireba. intaqturi adamianis sisxlis nimusebi mowodebuli iyo sisxlis gadasxmis institutis mier. nimusebis testirebas tetrahidrokanabinolis, benzoilekgoninis, metadonis, amfetaminebis, opiatebis da benzodiazepinebis Semcvelobaze vaxdendit heterogenuli imunofermentuli analizis (ELISA) eqspres metodit. sisxlis in vitro nimusebis momzadeba xdeboda Semdegi metodit - obieqtsi Segvyavda cnobili koncetraciis standartuli xsnari (5 mg/l), stabilizacias vaxdendit natriumis ftoridit da vinaxavdit 2-8 C temperaturaze. olanzapinis daslis Tavidan asacileblad, rogorc standartul ise saanalizo nimusebs vatavsebdit Suqdamcav qromatografiul flakonebsi. standartuli proceduris Tanaxmad, analizis dawyebamde sisxlis saanalizo nimusebs vwonidit da yovel 0.2 g sisxlis nimusss emateboda 25 mkl 25% askorbinis mjava. nimusebs cilebis daleqvamde frtxilad ematebolda 1000 mkl metanoli 0.6% formaldehidtan ertad. 10 wuti centrifugirebis Semdeg (3500 br/wt), xdeboda organuli nawilis mocileba da aqroleba 40 C temperaturaze azotis nakadis qves. nasts vxsnidit 200 mkl mozrav fazasi da vacentrifugirebdit kidev 10 wuti, gadagvqonda qromatografirebis flakonebsi da vaxdendit nimusis injeqtirebas aparatsi. aparaturuli gaformeba kvlevis dros viyenedit sitxur qromatografs mas spetrometrtan tandemsi (LC MS MS) - AGILENT TECHNOLOGIES 1290 Infinity AGILENT TECHNOLOGIES 6460 Triple quad LC/MS. olanzapini izleoda simetriul piks kargi Sekavebis droit Semdeg svetze - Zorbax Eclipse, stacionaruli faza - C18 ( mm, 1.8µµm). xelsawyo agretve arwurvili iyo winasvetit - UHPLC GUARD Zorbax Eclipse, stacionaruli faza - C18 (5 2.1mm, 1.8µm). ionizacia miirweoda dadebiti eleqtrogafrqvevit (ESI + ). skanireba mimdinareobda mravaljeradi reaqciebis monitoringit (MRM). olanzapinis saanalizod SerCeuli iqna sistema: 0.1% HCOOH (H2O):0.1% HCOOH (CH3CN)=60:40 (v/v). analizis xangrzlivaoba iyo 6 wuti. rejimi izokratuli, mozravi fazis dinebis sicqare 0.6 ml/wt, svetis temperatura 40 C 84

85 olanzapinis optimaluri MRM gadasvlebi aris m/z , m/z da m/z , rac SesaZlebels xdis movaxdinot arnisnuli nivtierebis rogor Tvisobrivi aseve raodenobrivi analizi sxvadasxva biologiur masalasi (nax. 2). nax. 2. olanzapinis tranzaqcia m/z kvlevis Sedegebis ganxilva. Catarebuli kvlevis Sedegad dadgenili iqna, rom olanzapini izleva simetriul, ukudo piks Sekavebis droit tt = wt, Semdegi mozravi fazis pirobebsi 0.1% ZmarmJavis wyalxsnaris da 0.1% ZmarmJavis xsnari acetonitrilsi (60:40)( v/v) SefardebiT, C 18 svetze. (nax. 3). SemuSavebuli metodi warmatebit iqna gamoyenebuli sisxlis in vitro nimusebsi olanzapinis arsebobis dasadastureblad (nax. 3). nax. 3. olanzapinis analizis miznit LC/MS/MS optimaluri pirobebis SerCeva sxvadasxva tranzaqciebis pirobebsi daskvna. SemuSavebuli iqna adaminis sisxlsi olanzapinis gansazrvis martivi, mgrznobiare da efeqturi metodi. igi sasualebas izleva dadgenili iqnas olanzapinis arseboba rogorc individualuri minoruli raodenobis arsebobis, aseve sxva preparatebtan ertdrouli gamoyenebis dros. 85

86 literatura 1. Meltzer H.Y., Fibiger H.C. Olanzapine: A new atypical antipsychotic drug. Neuropsychopharmacology 1996; 14: Medicinal Product Statistic in Denmark /db/filarkiv/6686/kapitel1.pdf, September Baselt R.C. Disposition of Toxic Drugs and Chemicals in Man. 7th ed. Chemical Toxicology Institute. Foster City, CA: 2004; Aravagiri M., Ames D., Wirshing W.C., Marder S.R. Plasma level monitoring of olanzapine in patients with schizophrenia: Determination by high-performance liquid chromatography with electrochemical detection. Ther. Drug Monit. 1997; 19: Robertson M.D., McMullin M.M. Olanzapine concentrations in clinical serum and postmortem blood specimens when does therapeutic become toxic? J. Forensic Sci. 2000; 45: Ulrich S. Assay of olanzapine in human plasma by a rapid and sensitive gas chromatography nitrogen phosphorus selective detection (GC NPD) method: validation and comparison with highperformance liquid chromatography coulometric detection. Ther.Drug Monit. 2005; 27: Sachse J., Koller J., Hartter S., Hiemke C. Automated analysis of quetiapine and other antipsychotic drugs in human blood by high performance-liquid chromatography with column-switching and spectrophotometric detection. J. Chromatogr. B Anal.Technol. Biomed. Life Sci. 2006; 830: Saracino M.A., Gandolfi O., Dall Olio R., Albers L., Kenndler E., Raggi M.A. Determination of Olanzapine in rat brain using liquid chromatography with coulometric detection and a rapid solid-phase extraction procedure. J. Chromatogr. A 2006; 1122: Catlow J.T., Barton R.D., Clemens M., Gillespie T.A., Goodwin M., Swanson S.P. Analysis of olanzapine in human plasma utilizing reversed-phase high-performance liquid-chromatography with electrochemical detection. J. Chromatogr. B 1995; 668: (1995). 10. O.V. Olesen and K. Linnet. Determination of olanzapine in serum by high-performance liquid chromatography using ultraviolet detection considering the easy oxidizability of the compound and the presence of other psychotropic drugs. J. Chromatogr. B. 1998; 714: Nirogi R.V.S., Kandikere V.N., Shukla M., Mudigonda K., Maurya S., Boosi R., Yeffamilli A. Development and validation of a sensitive liquid chromatography/electrospray tandem mass spectrometry assay for the quantification of olanzapine in human plasma. J. Pharm. Biomed. Anal. 2006; 41: Niederlander H.A.G., Koster E.H.M., Hilhorst M.J., Metting H.J., Eilders M., Ooms B., de Jong G.J. High throughput therapeutic drug monitoring of clozapine and metabolites in serum by on-line coupling of solid phase extraction with liquid chromatography mass spectrometry J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2006; 834: Bao J.Q., Potts B.D. Quantitative determination of olanzapine in rat brain tissue by high-performance liquid chromatography with electrochemical detection J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2001;752: Kollroser M., Schober C. Direct-injection high performance liquid chromatography ion trap mass spectrometry for the quantitative determination of olanzapine, clozapine and N-desmethylclozapine in human plasma. Rapid Commun. Mass Spectrom. 2002; 16: Kirchherr H., Kuhn-Velten W.N. Quantitative determination of forty-eight antidepressants and antipsych. in human serum approach. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2006; 843: reziume olanzapinis gansazrvra adamianis sisxlsi sitxur qromatografiuli mas speqtrometruli (LC/MS/MS) metodit 1 murtazasvili T., 1 maxaraze r., 1 sivsivaze k., 1 imnaze n., 2 joxaze m., 2 TuSuraSvili p. 1 Tbilisis saxelmwifo samedicino universitetis farmacevtuli da toqsikologiuri qimiis departamenti; 2 ssip levan samxaraulis sasamartlo eqspertizis erovnuli biuros qimiur-narkologiuri departamenti, saqartvelo 86

87 SemuSavebulia martivi, mgrznobiare da swrafi sitxur qromatografiul - mas speqtrometruli (LC/MS/MS) metodi olanzapinis gansazrvris miznit mtlianad sisxlsi. sisxlis nimusebsi SemJavebuli metanolit cilebis daleqvis Semdeg, saanalizo obieqtebis da olanzapinis referens standartis qromatografireba mimdinareobda Seqcevad fazian svetze Zorbax Eclipse plus C18 ( mm, 1.8µm), romelic arwurvilia wina svetit: UHPLC GUARD Zorbax Eclipse plus C18 (5 2.1 mm, 1.8µm). mozravi fazis saxit mowodebulia: WianWvelmJavas 0.1% xsnari wyalsi : WianWvelmJavas 0.1% xsnari acetonitrilsi = 60 : 40 (v/v), dinebis sicqare 0.6 ml/wt. svetis temperatura qromatografirebis dros iyo 40 C. zemot arwerili metodi sasualebas izleva mivirot olanzapinis simetriuli piki kudis garese, romlis Sekavebis sasualo dro aris wt. deteqtireba mimdinareobda sammag quadropolian mas-speqtrometrze, romelic arwurvilia dadebiti eleqtrogafrqvevis mowyobilobit (ESI + ) da askanerebs mravaljeradi reaqciebis monitoringis (MRM) rejimsi. saerto qromatografirebis dro aris 6 wt. olanzapinis optimaluri MRM gadasvlebi aris m/z , m/z da m/z , rac SesaZlebels xdis movaxdinot arnisnuli nivtierebis rogor Tvisobrivi, aseve raodenobrivi analizi sxvadasxva biologiur masalasi. SemuSavebuli metodi warmatebit iqna gamoyenebuli sisxlis in vitro nimusebsi olanzapinis arsebobis dasadastureblad da misi gamoyeneba SeiZleba rogorc intoqsikaciebis, ise letaluri gamosavlis dros. SUMMARY DETERMINATION OF OLANZAPINE IN WHOLE BLOOD USING LIQUID CHROMATOGRAPHY TANDEM MASS SPECTROMETRY (LC/MS/MS) 1 Murtazashvili T., 2 Jokhadze M., 1 Makharadze R., 1 Sivsivadze K., 1 Imnadze N., 2 Tushurashvili P. 1 Tbilisi State Medical University, Department of Pharmaceutical and Toxicological Chemistry; 2 Levan Samkharauli National Forensics Bureau, Chemical-Narcological Department, Georgia Were developed the simple, sensitive and rapid Liquid Chromatography Tandem Mass Spectrometry (LC/MS/MS) method for determination of olanzapin in whole blood. After acidic methanol-induced protein precipitation of the whole blood samples and olanzapine reference standard were chromatographed on a reversedphase Zorbax Eclipse plus C18 ( mm, 1.8µm) column, equipped with pre-column: UHPLC GUARD Zorbax Eclipse plus C18 (5 2.1 mm, 1.8µm). Was used the mobile phase: 0.1 % water solution of formic acid (H 2 O) : 0.1 % acetonitrile solution of formic acid = 60 : 40 (v/v), flow rate 0.6 ml/min. Column temperature was 40 C. The described condition causes good resolution and without extensive peak tailing and with mean retention time min. Determination was performed on a triple-quadrupole mass spectrometer employing electrospray ionization technique (ESI + ) operating in multiple reaction monitoring (MRM) and positive ion mode. Total chromatographic run time was 6 min. The optimized MRM transitions for olanzapine were m/z , m/z and m/z as the quantitative and confirmative traces, respectively. The method was subsequently applied to in vitro blood samples for determination of olanzapin. The received data gives the opportunity of forensic investigation of the intoxication or postmortem cases. 87

88 CONCEPTUAL APPROACHES TO THE TIERED PHARMACEUTICAL EDUCATION Prokopenko T., Kotvitska A. National University of Pharmacy, Kharkov, Ukraine The modern system of professional education in Ukraine goes through rapid changes that are caused both integration into the European educational space, and focus on the national requirements to the professional level of specialists. Therefore in the country series of steps for the modernization of higher education have been undertaken. The adoption of the National Qualifications Framework of sector standards of higher education is among them. Also the quality training of specialists in pharmacy is given by the approved standards of Good pharmacy practice in Ukraine. The main purpose of pharmaceutical education is to prepare the competent specialist who is ready for professional growth, and is able to self-education and self-improvement. Content of education, and forms and methods of teaching should be focused on the formation of professional competence of specialists in pharmacy to obtain the necessary information, to analyze production problems, to find ways of their rational solutions and to be able to adapt professional knowledge to solve new practical tasks. Realization of idea of continuing (further) education in the pharmaceutical industry has started with the implementation of level system of higher education. It has allowed expanding possibilities to obtain higher education gradually, i. e. by the levels. Educational and professional trainings become more flexible, and specialists professional protection in labor market conditions becomes more enhanced. Every educational level in pharmacy has specific purpose and tasks. However, it is a part of the continuing education. Various durations of studies are set for every level. The layered training of specialists assumes new approaches to the methodical maintenance of the educational process, and development of integrated curricula and programs. Advisability of functioning of each level is due to economic needs. Its professional completion depends on the personality motivation, account of the demand in developing of this educational level among the population of the region, and providing new opportunities for higher educational levels. Currently there are four levels of higher pharmaceutical education in Ukraine. About fifty percent of students which have Junior Specialist Diploma study in National University of Pharmacy over a shortened integrated plan. More than seventy percent of graduates of colleges of pharmacy enter the next level in the University immediately after graduation. About fifteen percent of graduates not continue studying immediately in the first year. The opportunity to combine education and work on a specialty allows many students get a complete pharmaceutical education. Implementation of tiered training of higher education provides great opportunities for personality formation, offers flexibility of a comprehensive, cultural and scientific training of specialists, improving their social status in the labor market and the integration into the global educational community. 88

89 fluoqsetinis raodenobrivi gansazrvris metodis damusaveba adamianis sisxlis plazmis modelze gvritisvili g., kunwulia l., WumburiZe b., joxaze m. Tbilisis saxelmwifo samedicino universiteti farmacevtuli da toqsikologiuri qimiis departamenti, saqartvelo fluoqsetini (prozaki, nuzaki da a.s.) antidepresantuli sasualebaa. igi warmoadgens serotoninis ukusewovis seleqtiur blokators.mmiuxedavad imisa, rom ukanasknel xans farmacevtul bazarze gamocnda mravali axali antidepresanti, fluoqsetini mimdinare etapze lideris pozicias inarcunebs [1]. fluoqsetini farmakokinetikuri parametrebit miekutvneba riskis jgufis preparats [3]. literaturuli monacemebit preparatis ganawilebis moculoba VD=2500l/70kg; naxevargamoyofis periodi T 1/2 =1-3 dre; aqtiuri metabolitis norfluoqsetinis T 1/2 = 4-16 dre. am parametrebis mixedvit organizmsi adgili aqvs fluoqsetinisa da norfluoqsetinis dagrovebas da arasasurveli toqsikuri movlenebis ganvitarebas [3,6]. fluoqsetini warmoadgens R da S enantiomerebis racemul narevs 50/50.Ddadgenil iqna, rom S-enantiomers gaacnia ufro marali antidepresiuli efeqti, vidre R-enantiomers [6]. orive enantiomeri desmetiltransferazas moqmedebit RviZlSi ganicdis metabolizms demetilirebis gzit da warmoiqmneba ufro aqtiuri metabolitis norfluoqsetinis R da S enantiomerebi (sur. 1) [6,7]. sur. 1. fluoqsetinis metabolizmi msoflio mosaxleobis 7% daqveitebuli aqvs fermentuli aqtivoba da wamlebis metabolizmis sicqare. aset adamianebs Rarib metabolurebs uwodeben [4]. fluoqsetinis metabolizmsi monawileobs citoqrom P450, romelsac axasiatebs genetikuri polimorfizmi [6,8] wels armocenil iqna fluoqsetinis metabolizmis sicqaris mixedvit pacientta sxvadasxva fenotibebi _ swrafi da neli demetilatorebi; pirvelad am SemTxvevaSi moxda dozebis koreqcia individualuri pacientis fenotipze dayrdnobit, ramac Seamcira wamlis toqsikuri Tvisebebi [4]. kvlevis mizani saqartvelosi fluoqsetinze farnakokinetikuri kvlevis Casatareblad maralefeqturi sitxuri qromatografiuli metodis damusaveba modelze. 89

90 Qqromatografirebis optimaluri pirobebis dadgena: sorbentisa da mozravi fazis SerCeva; plazmidan fluoqsetinis izolirebis metodebis SedarebiTi daxasiateba: eqstraqciulisa da daleqviti; fluoqsetinis standartuli nimusis mireba prozakis kafsulebidan da misi ketilxarisxovnebis Sefaseba standartizaciis Tanamedrove metodebit. kvlevis masala da metodebi. intaqturi adamianis sisxlis plazma; prozakis kafsulebi (ass). kvlevis metodebi speqtrofotometria _ СФ-46 da Chimazu ; infrawiteli speqtrometria _ Perkinelmer speqtrum 100 ; maralefeqturi sitxuri qromatografia _ WATERS ultraiisferi da dioduri deteqtorit(dad), romelic xasiatdeba speqtris farto diapazonit nm; mass-speqtrometri-sitxuri qromatografia _ tandemuri MS/MS. eqsperimentuli nawili. modelis damusaveba adamianis sisxlis plazmidan moitxovda fluoqsetinze standartis arsebobas. saqartvelosi fluoqsetinis standartis ar arsebobis gamo Cven gamovyavit standarti fluoqsetinis kafsulebidan: fluoqsetinis kafsulebi - dozit 20mg, seria: ; virebdit 20 kafsulas; fuoqsetinis substancias vatavisuflebdit kafsulebidan, vatavsebdit 50ml-ian qimiur WiqaSi, vumatebdit 20ml metanols da vanjrrevdit magnitur sarevelaze 15wT ganmavlobasi, vfiltravdit unacro filtrsi, filtrats vaortqlebdit vakuum aparatsi; vrebulobdit TeTri feris fxvnils da vatarebdit mirebuli fluoqsetinis substanciis analizs Tanamedrove speqtraluri da qromatografiuli metodebit. fluoqsetinis sisuftavis dasadgenad pirvel etapze gamoviyenet speqtrofotometria ultraiisfer ubansi misi qimiuri struqturidan gamomdinare [3]; mnisvnelovania misi sami fragmenti: fenoluri, triftor-metiluri da fenoqsi jgufi (sur. 2). sur. 2. Ffluoqsetini arnisnuli fragmentebi ganapirobeben fluoqsetinis STanTqmis sxvadasxva maqsimumebs sxvadasxva talris sigrzeze. Cven gadaviret fluoqsetinis STanTqmis speqtrebi ultraiisfer ubansi sxvadasxva gamxsnelebsi: qloroformsi da metanolsi. qloroformsi dafiqsirda STanTqmis ori maqsimumi 265 da 350 nm-ze, xolo metanolsi sami STanTqmis maqsimumi 230nm, 280nm da 330nm-ze, rac Seesabameba fluoqsetinis standarts [3]. fluoqsetinis sisuftave davadginet infrawiteli speqtroskopiit da massspeqtrometriuli metodit (sur. 3, 4). 90

91 sur. 3. fluoqsetinis infrawiteli speqtri sur. 4. fluoqsetinis mass-speqtri M/Z-310 fluoqsetini M/Z-148 Svilobili ioni mass-speqtrze arinisneba erti maqsimaluri simarlis piki - M/Z-310, romelic Seesabameba fluoqsetins da erti minimaluri simarlis piki _ Svilobili ioni - M/Z- 148, romelic Seesabameba 3-ftor_fenoqsi_ionis fragments. Mmass-speqtrograma emtxveva literaturul monacemebs. fluoqsetinis standartuli nimusis ketilxarisxovnebis dadgenis Semdeg eqsperimentis meore etapze davamusavet intaqturi adamianis sisxlis plazmidan misi izolirebis modeli, ristvisac viyenebdit daleqvit da eqstraqciul metodebs. plazmasi fluoqsetinis koncentracias vsazrvravdit maralefeqturi sitxuri qromatografiuli metodit _ sitxuri qromatografi (waters), deteqtori dioduri ultraiisferi; talris sigrze 258nm; sveti- sorbenti-silikageli C 18 nawilakta zoma 1.5, mozravi faza- acetonitrili : acetaturi buferi 20:80 TanafardobiT; rejimi izokratuli; gamxsnelta dinebis sicqare 0.3 ml/wt; 91

92 fluoqsetinis indentifikacia xdeba Sekavebis drois mixedvit. (ix. sur. 5). sur. 5. fluoqsetinis qromatograma ( Sekavebis dro_0.57) qromatogramaze vrebulobdit mxolod ert piks Sekavebis droit 0.57wT, rac fluoqsetinis igiveobasa da sisuftaveze miutitebs. fluoqsetinis raodenobas vsazrvravdit absoluturi dakalibrebis metodit, ristvisac vamzadebdit fluoqsetinis substanciis standartuli nimusisgan seriuli koncentraciebis ganzavebul xsnarebs 5-100ng farglebsi. intaqturi adamianis sisxlis plazmis TiTo ml-si Segvqonda fluoqsetinis cnobili koncentraciebi mkg/ml-si. fluoqsetinis izolirebas plazmidan vaxdendit acetonitrilit-daleqviti da qloroformit-eqstraqciuli metodebit. vagebdit sakalibro grafikebs, yvela SemTxvevaSi: wyliani xsnarebis; qloroformit eqstraqciisa da acetonitrilit daleqvisas qromatografsi gatarebuli xsnarebis pikebis simetriuloba sasualebas izleva preparatis koncentracia gamogvetvala misi simarlis (H mm) mixedvit. pikis simarlesa da koncentracias Soris arinisneba sarwmuno korelacia: korelaciis koeficienti meryeobs Soris, ris gamoc fluoqsetinis raodenobrivi gansazrvisatvis SesaZlebelia gamoyenebul iqnas absoluturi dakalibrebis metodi. qloroformit eqstraqciis SemTxvevaSi maralefeqturi sitxuri qromatografiuli metodis cdomileba Seadgens 2.5%, xolo acetonitrilit daleqvisas 3.83%. rogorc metodebis SedarebiTi daxasiatebidan Cans, pirvel SemTxvevaSi metodis cdomileba ufro naklebia, vidre meore SemTxvevaSi, magram meore SemTxvevaSi analizis dro 2-jer naklebia, rac zrdis metodis kvlavwarmoebulobas. daskvnebi. damusavebul iqna fluoqsetinis standartuli nimusis gamoyofis metodika safirmo preparatebidan prozakis kafsulebidan. fluoqsetinis standartisadmi Sesabamisoba Seswavlil iqna: maralefeqturi sitxuri qromatografiuli, ultraiisferi da infrawiteli speqtrofotometriuli da qromatomass-speqtrometriuli metodebit. damusavebul iqna fluoqsetinis izolirebis metodi intaqturi adamianis sisxlis plazmidan: eqstraqciuli da daleqviti. dadgenil iqna fluoqsetinis eqstragirebis xarisxi qloroformit _ 92.35%, metodis cdomileba ±2.5%; dadgenil iqna fluoqsetinis gamontavisuflebis xarisxi acetonitrilit daleqvisas _ 86.5%; metodis cdomileba ±3.83%. damusavebul iqna modeli adamianis sisxlis plazmidan fluoqsetinis izolirebis da raodenobrivi gansazrvris maralefeqturi sitxuri qromatografiuli metodit, 92

93 talris sigrze 258nm; SerCeul iqna qromatografirebis optimaluri pirobebi: mozravi faza: acetonitrili : acetaturi buferi 20:80, sorbenti-silikageli C 18, rejimi izokratuli, metodis mgrznobeloba 1ng, cdomileba ±1.5%. literatura 1. Катцунг Г. Базисная и клиническая фармакология Harvey AT, Preskorn SH. Fluoxetine pharmacokinetics. J. Clinical psychopharmacology 2001; Mandrioli R., Forti Gc, Raqqi MA. Fluoxetine metabolizm. Cuur Drug Metabolizm 2006; Klein Chand T.E., Cho M.K., Easton K.L. Interating genotype and Phenotype information, an overview of the Pharm GRB Project. J. Pharmacogenomics 2001; Mandrioli R., Pucci V., Visini D. Rapid methods for determination of fluoxetine in pharmaceutical formulations. 2002; ; 6. Erturk S., Cetin SM, Atmaca S. A sensitive HPLC method for the determination of fuoxetine and norfluoxetine in human plasma with fluorescence detection. 2005; Bramley RK, Bulock DG, Garcia JR. Quality control and assesment in Clarkes analysis of drugs and poisons,editors. Pharmaceutical press 2005; Darwish I.A, Sawsan M. New Speqtrophotometric methods for determination of fluoxetine. International juornal of Analytical of Chemistry 2009; Wille SMR, Maudes KE, Peteghem CHv Development of a solid phase extraction for 13 new generation antidepressants and their metabolites for gas chromatography-mass speqtrometry.2005; Jagadeesweren M., Mahibalan S. International Journal of Pharmacy and Pharmaceutical science 2009; 1: SUMMARY METHOD FOR DETERMINING THE QUANTITY OF FLUOXETINE ON THE MODEL OF HUMAN BLOOD PLAZMA Gvritishvili G., Kunchulia L., Chumburidze B., Jokhadze M. Tbilisi State Medical University, Department of Pharmaceutical and Toxicological Chemistry, Georgia Fluoxetine takes the leading position in the world among the curing antidepressant means of new generation. It presents the selective medicine of back absorption of serotonin. Fluoxetine belongs to the risk group medicine by pharmacodynamic and pharmacokinetic parameters; Distribution volume Vd = 2500 L/70 kg; the period of half secretion T 1/2 =1-3 day, active metabolism norfluoxetine T 1/2 =4-16 day; form side effects of the medicine there should especially note cardiotoxicity, that is often finished by attempt of suicide and lethal facts. According to the literary data the safe and effective treatment with fluoxetine is in correlation with the peculiarities of its metabolism and the genetic polymorphism of ferments. There were the incidents of patients intoxication after taking the abnormal doze of this medicine in Georgian population. Mentioned medicine is also used for treating bulimia and it is often included in the biological food additives of uncertain origin and non-registered curing means. Due to everything mentioned above, the goal of our research was to work out the high-effective liquid chromatography method for determining the quantity of fluoxetine on human blood plasma (on the model) in Georgian population. The methods of research: high-effective liquid chromatography. Apparatus ultra-effective liquid chromatography water (USA), ultra-violate diode dedector; Definition took place on the wave length λ -258 nm. Sorbent- Silicogel C 12 size 1.5 M ; movable phase acetonitrile acetetive buffer- in proportion 20:80; speed of solvents flow 0.3 ml/m; regime izocrative; sensibility of the method 1ng/ml; fault of the method ±1.5% 93

94 The method provided by us gives possibility to define the quantity of fluoxetine concentration in the plasma of human blood in the frames of ng, that is reliable for making the monitoring of fluoxetine concentration in the plasma of patient s blood for the purpose of safe and effective treatment and also from the view of court-expertise. amlodipinis besilatis qromatografiuli analizi - analizuri metodis ganvitareba cercvaze al., WumburiZe b., kobaxize q., CikvilaZe T., otarasvili T. farmacevtuli kompania,,ji-em-pi -s kvlevisa da testirebis laboratoria Tbilisis saxelmwifo samedicino universiteti, farmacevtuli da toqsikologiuri qimiis departamenti, saqartvelo gul-sisxlzarrvta sistemis daavadebebi Tanamedrove msoflios ert-erti yvelaze mnisvnelovani problemaa. ganvitarebad qveynebsi da mat Soris saqartvelosic, es daavadebebi adamianta Sromisunarianobis dakargvis da sikvdilianobis mtavar gamomwvev mizezad miicneva. cnobilia, rom gulis musaoba da sisxlzarrvebis tonusi mnisvnelovnad aris damokidebuli kalciumis ionebis cvlaze. kerzod, mat ganawilebaze ujredis SigniT da garet. amitom, Zalze sainteresoa kalciumis ionebis kinetikis martvis SesaZleblobis arseboba. ert-erti aseti gzaa kalciumis arxebis blokireba. kalciumis arxebis blokatorebis mravalricxovani jgufidan ert-erti yvelaze gamocdili da efeqturia II Taobis warmomadgeneli - amlodipini. Sromis mizani - amlodipinis besilatis Semcveli medikamentis (,,adipini 10 mg ) analizuri metodis ganvitareba. kvlevis masala da metodebi. kvlevis masalas warmoadgenda: amlodipinis besilatis substancia,sveicaria CHEM Line, (seria AB, vada mde), amlodipinis standartuli nimusi (USP, seria: Lot:GOF133), qartuli farmacevtuli sawarmo GMP-is mier warmoebuli preparati,,adipini 10 mg tableti (seria ), originali preparati,,norvaski 10 mg tableti pfaizeri, germania ( ser: A ), amlodipinis besilatis msgavsi struqturis mqone nivtierebebis Semcveli preparatebi (anu dihidropiridinis warmoebulebi)-,,nifedipini 10,0 mg tableti (Balkanfarma, bulgareti),,,nimotopi 30,0 mg tableti (Bayer AG, germania) da,,lerkameni 10,0 mg tableti (Berlin- Chemie, germania). kvlevisatvis gamoyenebuli iqna maralefeqturi sitxuri qromatografiuli metodi substanciis identifikaciis, raodenobrivi da garese minarevebis gansazrvrisatvis, raodenobrivi gansazrvris da armocenis zrvrebis dadgenisatvis, metodis specifiurobis, sizustis, sworxazovnebis da analizuri metodis mdgradobis Sesaswavlad, agretve adipini 10 mg tabletebis gamowvlilvis xarisxis Sesaswavlad, raodenobrivi, garese minarevebis, identifikaciisa da xsnadobis gansazrvrisatvis, xsnadobis profilis SeswavlisTvis, dozirebis ertgvarovnebis dadgenistvis. eqsperimentuli nawili: substanciaze Catarebuli testebi - metodis damusavebis dros vixelmzrvanelet farm-statiebit amlodipinis besilatze evropis, britanetis da amerikis farmakopeebis moqmed gamocemebsi da svetad SerCeul iqna oqtadecilsilikageli Eclipse XDB C18, nawilakebis zomit 5 mkm. svetis zomebi: 4,6 mm X 250 mm (nacvlad farmakopeasi mititebuli 3,9 mm X 150 mm). nakadis sicqare 1,0 ml/wt, deteqtirebistvis amlodipinis ultraiisfer speqtridan gamomdinare 237±2 nm, Sesayvani 94

95 sinjis moculoba-20 mkl. mozravi faza m fosfaturi buferi/acetonitrili (ph=3,0) (6:4 moc/moc). specifikuroba - mocemuli metodis specifikurobis Sesaswavlad gavaanalizet amlodipinis besilatis msgavsi struqturis mqone nivtierebebi (anu dihidropiridinis warmoebulebi) nifedipini, nimodipini da lerkanidipini. Sesabamisi preparatebidan momzadda 0,1 mg/ml koncentraciis xsnarebi. Sekavebis dro: amlodipinis besilati - 4,3 wt; nifedipini 18,2 wt; lerkanidipini 35,3 wt da nimodipini 61,5 wt. nax. 1. metodis specifikurobis gansaxrvris grafiki (amlodipini besilati, nifedipini, lerkanidipini, nimodipini) sizuste - metodis sizustis Sesafaseblad momzadbul iqna amlodipinis besilatis 0,02 mg/ml koncentraciis xsnari. dadgenil iqna Semdegi parametrebi: a) ganmeorebadobaaamlodipinis besilatis standartuli xsnaris eqvsjeradi inicirebit da gaangarisebul iqna standartuli da fardobiti standartuli gadaxrebi inicirebebs Soris - SD= 0.53%; RSD= 0.07% b) Sidalaboratoriuli sizuste erti analitikosis mier momzadebuli xsnarebi gaanalizebul iqna sam sxvაdasxva dresi ertidaigive xelsawyoze- SD=0,11-0,22-0,48%; RSD=0,01-0,03-0,07%. g) laboratoriatsorisi sizuste (kvlavwarmoebuloba) dasabutebul iqna xsnarebis gaanalizebit sxvadasxva xelsawyoze ( Agilent 1200 QCL/04/30 da Agilent 1200 QCL/04/31) sxvadasxva svetis gamoyenebit (Eclipse XDB C 18 da Zorbax SB C 18). Eclipse XDB - SD =0,28%; RSD= 0,04%; Zorbax SB - SD =0,59%; RSD= 0,08%. metodis sworxazovneba - metodis sworxazovnebis dasadgenad movamzadet amlodipinis besilatis standartuli nimusis ZiriTadi xsnari koncentraciit 0,1 mg/ml, romlis ganzavebebit mirebul iqna Semdegi koncentraciis xsnarebi : 0,02 mg/ml; 0,01 mg/ml; 0,005 mg /ml; 0,0025 mg/ml. xsnarebis samjeradi inicirebita da mirebuli Sedegebis damusavebit agebul iqna koncentraciasa da fartobebs Soris damokidebulebis grafiki. S 4000, , ,00 y = x R² = ,00 C(მკგ/მლ) 0,00 0,00 20,00 40,00 60,00 80,00 100,00 120,00 nax. 2. metodis sworxazovnebis sakalibro grafiki 95

96 raodenobrivi gansazrvrisa da armocenis zrvrებi- dadgenil iqna, rom amlodipinis besilatis raodenobrivi gansazrvris (LOQ) zrvaria 7,8 ng/ml (xmauri /signali 1:11,8), xolo deteqtirebi(lod) 3,9 ng/ml(xmauri /signali 1:5,2). nax. 3. deteqtirebis zrvrებi analizuri metodis mdgradoba - metodis mdgradoba Seswavlil iqna sxvadsxva parametrebis cvlilebebis ganxorcielebit, kerzod, mobiluri fazis ph-isa dahorganuli da araorganuli komponentebis Tanafardobis, deteqtirebistvis SerCeuli talris sigrzis cvlilebis, agretve svetis temperaturisa, tipis da sigrzis cvlilebebis gavlena amlodipinis besilatis Sekavebis droze da fartobze.mirebuli monacemebidan gamomdinare mozrav fazasi organuli nawilis gazrda iwvevs pikis gamosvlis drois Semcirebas,xolo talris sigrzis cvlileba ±2 nm-is farglebsi ar axdens mnisvnelovan gavlenas amlodipinis besilatis STanTqmaze. svetis temperaturis cvlileba 20 C-40 C aseve ar axdens mnisvnelovan gavlenas Sekavebis droze,xolo nakadis sicqaris matebit mcirdeba amlodipinis besilatis Sekavebis dro. rogorc mosalodneli iyo, svetis sigrzis cvlilebam gamoiwvia amlodipinis pikis adre gamosvla (2,7 wt), xolo svetis tipis cvlilebam (Eclipese Seicvala Zorbax-iT) pikis dagvianebit gamosvla (5.5 wt). amlodipinis besilatis substanciis identifikaciis, minarevebis da raodenobrivi Semcvelobis analizi Catarda evropis farmakopeasi arwerili metodis mixedvit. sakvlev substanciasi amlodipinis besilatis raodenobrivi Semcvelobis sasualo macvenebeli iyo % (norma: 97, %-mde). amlodipinis besilatis substanciasi ganvsazrvret specifikuri D (3-eთიl 5-meთიl 2-[(2- aminoeთოქსი)meთიl]-4-(2-ქloroფენილ)-6-meთიlpიridin-3,5-diკarboქსიlate) minarevis Semcveloba %( norma 0,3%), xolo minarebis jami 0.09% (norma 0,3%). nax. 4. amlodipinis besilatis specifiuri D minarevi 96

97 mza wamlis formaze Catarebuli testebi preparat adipinis tab. 10,0 mg gamowvlilvis xarisxis Seswavla mirebuli monacemebidan gamomdinare dadgenil iqna,rom gamxsnelis moculoba(100, 200, 500 ml) da dro(1, 2, 3 st) mnisvnelovan gavlenas ar axdens gamowvlilvis xarisxsze, xolo ultrabgeris(30wt) gamoyeneba mnisvnelovnad aumjobesebs gamowvlilvis xarisxs. raodenobrivi Semcvelobis gansazrvris Sedegi - 9,904 mg (zrvari 9,25-10,75 mg) preparat adipinis xsnadobis profilis Sedareba original preparat norvasktan sam sxvadasxva farmakopeul aresi - adipinisa da norvaskis sxvadsxva aresi xsnadobis msgavsebis dasadastureblad, Catarda sacdeli seriis xsnadobis profilis Sedareba original preparattan sam sxvasxva buferul aresi (qloriduli buferuli xsnari ph 1,2; acetaturi buferuli xsnari ph 4,5 da fosfaturi buferuli xsnari ph 6,8). buferuli xsnarebi momzadda amerikis farmakopeis mixedvit, aris moculoba 500,0 ml, brunvis sicqare 100 br/wt, temperatura 37±0,5 C, sinjebis arebis dro: 5, 10, 15 da 30 wt. mirebuli Sedegebis safuzvelze agebul iqna gamotavisuflebuli aqtiuri nivtierebis raodenobis drostan damokidebulebis grafikebi gaangarisebul iqna msgavsebisa (f 2 ) (norma ) da gansxvavebis (f 1 ) (norma 0-15) koeficientebi. ph1,2 (f 1 2,13 da f 2 85,61); ph4,5 (f 1 3,19 da f 2 79,78); ph6,8 (f 1 1,91da f 2 88,72). G 100 % ნორვასკი ph 1.2 ადიპინი ph 1.2 ადიპინი ph 4.5 ნორვასკი ph 4.5 ადიპინი ph 6.8 ნორვასკი ph წთ 30 nax. 5. adipinisa da norvaskis xsnadobis profili amlodipinis in vitro xsnadobis gansazrvra preparat adipinsa da original preparat norvasksi. preparat adipinis xsnadobis aris SerCevisas vixelmzrvanelet amerikis farmakopeasi arsebuli statiit amlodipinis besilatis tabletebze. xsnadobis ared SerCeul iqna 0,01 n qlorwyalbadmjava. analizi Catarda sitxur qromatografze Agilent 1200, mirebuli Sedegebis safuzvelze agebul iqna gamotavisuflebuli aqtiuri nivtierebis raodenobis drostan damokidebulebis grafikebi. gaangarisebul iqna msgavsebisa (f 1 =2,72) da gansxvavebis (f 2 =81,95) koeficientebi. Sedegebidan gamomdinare koeficientebi normis farglebsia. nimusis arebis dro (wt) norvaski ტაბ. 10,0 მგ (%) ადიპინი ტაბ. 10,0 მგ (%)

98 % norvasc tab. 10 mg adipin tab. 10 mg Ddro(w T) 35 nax. 6. adipinisa da norvaskis in vitro xsnadoba preparat adipinsi 10 mg dozirebis ertgvarovnebis gansazrvra. testis Casatareblad saanalizod aviret preparatis adipini tab 10,0 mg 10 tableti da mirebuli Sedegebis safuzvelze gamoviangariset gadaxris dasasvebi mnisvnelobebi (AV) preparat adipini tab. 10,0 mg-tvis (amerikis farmakopea, tomi 1, ZiriTadi monografia <905>). cxrili 1. adipinsi 10 mg tabletebsi dozirebis ertgvarovnebis gansazrvra mg 9.58 mg 9.58 mg 9.73 mg 9.71 mg 9.86 mg 9.60 mg 9.60 mg 9.76 mg 9.78 mg Sedegi: gadaxra - 4,0982 % (norma ± 7,5%). minarevebis gansazrvra preparatebsi adipini tab. 10,0 mg da norvaski tab. 10,0 mg - analizi Catarda evropis farmakopeasi arwerili metodis mixedvit,specifiuri D minarevis Semcveloba,,adipinis 10 mg tabletsi armocnda -0,04%( norma 0,3%), xolo minarebis jami 0,18% (norma 0,3%). norvaski 10,0 mg tabletsi D minarevis Semcveloba - 0,03% (norma 0,3%),sxva minarevi ar fiqsirdeba. kvlevis Sedegebi: Catarebuli kvleviti samusaoebis safuzvelze davadginet, rom amlodipinis besilatis substancia da,,adipinis 10 mg tabletebi akmayofilebs farmakopeis motxovnebs raodenobrivi gansazrvris, xsnadobis testis da minarevebis Semcvelobis mixedvit. metodi gadaeca validaciis ganyofilebas analizuri validaciis Casatareblad. arnisnuli preparatis sacdel seriaze daigegma stabilurobis testis Catareba. literatura 1. Кукес В.Г., Фисенко B.П. Клиническая фармакология блокаторов медленных кальциевых каналов. М.: Ремедиум; Amlodipine Citizen Petition by Pfizer Inc. Available at: 3. Беликов В.Г. Фармацевтическая химия. М.: 2007; U.S. Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER), Guidance for industry: Bioavailability and bioequivalence studies for orally administered drug products general considerations, March British Pharmacopoeia ; USP34 official10/1/10-1/31/11usp Monografhs:amlodpine besylate tablets(<197>). 7. European Pharmacopoeia reziume amlodipinis besilatis qromatografiuli analizi - analizuri metodis ganvitareba cercvaze al., WumburiZe b., kobaxize q., CikvilaZe T., otarasvili T. 98

99 farmacevtuli kompania,,ji-em-pi -s kvlevisa da testirebis laboratoria Tbilisis saxelmwifo samedicino universiteti, farmacevtuli da toqsikologiuri qimiis departamenti, saqartvelo Seswavlil iqna,,adipini 10 mg tabletis analizuri metodis ganvitarebis testi da dadginda, rom amlodipinis besilatis substancia da,,adipinis 10 mg tabletebi akmayofilebs farmakopeis motxovnebs raodenobrivi gansazrvris, xsnadobis testis da minarevebis Semcvelobis mixedvit. metodi gadaeca validaciis ganyofilebas analizuri validaciis Casatareblad. arnisnuli preparatis sacdel seriaze daigegma stabilurobis testis Catareba. SUMMARY CHROMATOGRAPHIC ANALYSIS OF AMLODIPINE BESYLATE - ANALYTICAL METHOD DEVELOPMENT Tsertsvadze Al., Chumburidze B., Kobakhidze K., Chikviladze T., Otarashvili T. GM Pharmaceuticals Ltd. Research and Testing Laboratory; Tbilisi State Medical University, Department of phrmaceutical and Toxicological Chemistry, Georgia Development test of,,adipine 10 mg tablets was studied. It was established that, Amlodipine besylate substance and,,adipine 10 mg tablets comply with the requirements of the pharmacopeia according to,,asay determination,,,dissolution test and,,impurity content. The methot is transferred to the validation department for analytical method validation. For above mantioned preparation stability test is planned. meloqsikamis Semcveli medikamentebis xarisxis kontroli wiwilasvili e., CikvilaZe T., lasauri n., otarasvili T. Tbilisis saxelmwifo samedicino universiteti, farmacevtuli da toqsikologiuri qimiis departamenti; farmacevtuli kompania,,ji-em-pi -s xarisxis kontrolis laboratoria, saqartvelo antebis sawinaarmdego arasteroiduli preparatebi itvleba msofliosi yvelaze xsirad danisnuli wamlebis jgufad. yoveldriurad, 30 milionze meti adamiani moixmars romelime antebis sawinaarmdego arasteroidul preparats. arnisnuli preparatebis aseti aqtualoba sawiros xdis mati xarisxis uzrunvelyofisa da kontrolistvis gansakuterebuli meqanizmebis SemuSavebas wlis ivnisis Tvidan saqartvelosi igegmeba antebis sawinaarmdego arasteroiduli preparatebis receptit gasacem medikamentta jgufsi gadatana, Sesabamisad, gansakutrebuli yuradreba mieqceva mati xarisxis kontrolisa da uzrunvelyofis sakitxebs da Sesabamisi laboratoriuli kontrolis metodebasac. faqtis gatvaliswinebit, 2005 wlidan meloqsikamis 15 mg-iani tabletebis warmoeba, saxelwodebit kameloti, daiwyo qartulma farmacevtulma sawarmom ji-em-pim. xarisxiani da usafrtxo preparatis warmoebisatvis aucilebelia kamelotis tabletebis droebiti farmakopeis statiis damusaveba meloqsikamis 99

100 standartizaciisatvis ukve arsebuli farmakopeuli statiebis ganxilvisa da gaanalizebis safuzvelze. kvlevis masala da metodebi. kvlevis masalas warmoadgenda: meloqsikamis substancia (Sveicaria CHEMLine, (seria MLAH , vada mde), meloqsikamis standartuli nimusi (USP, kodi: QCL/06/2103 seria: QCL/06/2103-lot: FOE158), meloqsikamis F minarevis standartuli nimusi, kodi: QCL/06/2052GMF; qartuli farmacevtuli sawarmo GMP-is mier damzadebuli meloqsikamis Semcveli preparatis kameloti 15mg tabletebi (seria , vada: ) da preparati,,movalisi 15mg tabletebi (UCB, Sveicaria). kvlevisatvis gamoyenebuli iqna: analizis fizikuri metodebi tabletebis sasualo masis, xsnadobis gansazrvrisatvis; ultraiisferi speqtrofotometria --- substanciis identifikaciisa da raodenobrivi gansazrvrisatvis, agretve kamelotis 15 mg tabletebis xsnadobis, identifikaciisa da raodenobrivi gansazrvrisatvis; infrawiteli speqtrofotometria substanciis polimorfizmis gamosaricxad; maralefeqturi sitxuri qromatografia - meloqsikamis substanciasa da kamelotis 15 mg tabletebsi garese minarevebis gansazrvrisatvis. cxrili 1. meloqsikamis substanciis da kamelotis 15 mg tabletebis speqtrofotometriuli analizisatvis gamoyenebuli xelsawyoaparatura, xsnarebi, reaqtivebi da damxmare masalebi xelsawyo - aparatura xsnarebi, reaqtivebi, damxmare masalebi saswori analizuri LA 120 saswori analizuri CPA 225D ultraiisferi speqtrofotometri Agilent 8453 magnituri sarevela safiltravi sistema vakuum-tumboti qromatografiuli sisuftavis wylismisarebi aparati eleqtronuli wisqvili agatis rodinit. xsnadobis ganmsazrvreli xelsawyo ERWEKA DT LH natriumis hidroqsidi metanoli kaliumis dihidrofosfati qr.s. wyali Spricis filtri-0,45 µm zomis forebit. Sprici ertjeradi cxrili 2. meloqsikamis substanciis da kamelotis 15 mg tabletebis maralefeqturi sitxuri qromatografiuli analizisatvis gamoyenebuli xelsawyo- aparatura, xsnarebi, reaqtivebi da damxmare masalebi xsnarebi, reaqtivebi, damxmare xelsawyo - aparatura masalebi saswori analizuri natriumis hidroqsidi maralefeqturi sitxuri qromatografi: Agilent Technologies metanoli 100

101 magnituri sarevela safiltravi sistema vakuum-tumboti qromat. sufta wylis misarebi aparati ph-metri qr.s. wyali filtri-celulozis nitratis 0,45 µm zomis forebit. filtri-celulozis nitratis 0,45 µm zomis forebit. amoniumis dihidrofosfati amoniumis hidroqsidi izopropilis spirti eqsperimentuli nawili a) meloqsikamis substanciis analizi usualod,,kameloti 15 mg tabletebis farmakopeuli analizis dawyebamde aucilebeli iyo meloqsikamis substanciis Semowmeba. meloqsikamis substancia warmoadgens Ria yviteli feris fxvnils. misi identifikacia da raodenobrivi gansazrvra vawarmoet speqtrofotometriuli metodit meloqsikamis substanciis analizi CavatareT britanuli farmakopeis mixedvit. arnisnuli normatiuli dokumentit, meloqsikamis raodenobrivi gansazrvrisatvis mowodebulia uwylo aresi titvra. Tumca Cven davamusavet igiveobistvis gamoyenebuli speqtrofotometriuli metodi da raodenobrivi gansazrvra CavatareT substanciis identifikaciastan ertad. meloqsikamis raodenobrivi Semcvelobis gamokvlevisatvis speqtrofotometriuli metodis damusaveba mizansewonilad mivicniet im miznitac, rom rom misi gamoyeneba SemdgomSi SesaZlebeli iqneboda kamelotis tabletebis raodenobrivi analizisatvis. speqtrofotometriuli gansazrvris pirobebi: kiuvetis sisqe 10mm; talris sigrzis diapazoni 200nm-1000nm; STanTqmis maqsimumi 365 ± 2nm-ze. standartuli nimusis xsnars STanTqmis maqsimumi hqonda 364 nm talris sigrzeze, xolo sakvlevi substanciis xsnars STanTqmis maqsimumi hqonda 366 nm talris sigrzeze. sakvlev substanciasi meloqsikamis raodenobrivi Semcveloba iyo % (norma: 99,0-100,5%.) meloqsikamis substanciasi wylis Semcveloba ganvsazrvret gamosrobis metodit: wylis procentuli Semcveloba meloqsikamis substenciasi iyo 0.394% (norma 0,5%) meloqsikamis substanciasi garese minarevebi ganvsazrvret maralefeqturi sitxuri qromatografiuli metodis gamoyenebit: 4-hidroqsi-2-meTil-2H-1,2-benzoTiazini-3karbomJavis etilis eteri 1,1 dioqsidi (minarevi A) % (norma 0,1%); 2-amino-5-meTilTiazoli (minarevi B) 0,0026% (norma 0,1%); 4- hidroqsi-2-metil-n-(n-metil-5-metil-2-tiazolil)-2h-1,2 benzotiazini-3-karboqsamidi- 1,1dioqsidi (minarevi C) % (norma 0.005%); 4-hidroqsi-2-meTil-N-(N-eTil-5-meTil-2- Tiazolil)-2H-1,2-benzoTiazini-3-karboqsamidi-1,1dioqsidi (minarevi D) % (norma 0.05%); jamuri minarevebis Semcveloba araidentificirebadi minarevebis gatvaliswinebit Seadgenda 0.077%-s (norma 0.3%). polimorfizmis gamosaricxad meloqsikamis substanciis analizi vawarmoet infrawiteli speqtrometruli metodit. meloqsikamis substanciis infrawiteli speqtri srul TanxvedraSi iyo literaturasi mocemul meloqsikamis standartis speqtrtan. 101

102 nax. 1. meloqsikamis standartuli nimusis da sakvlevi substanciis infrawiteli speqtrebi b) meloqsikamis Semcveli preparatis - kamelotis 15mg-iani tabletebis analizi: meloqsikamis Semcveli kamelotis 15mg tabletebis analizi vawarmoet saxelmwifo farmakopeis meore tomis, amerikuli farmakopeis [USP 3, 2610 Meloxicam / Official monographs] da qartuli farmacevtuli sawarmo GMP-is mier damusavebuli Sida (InHouse) metodebit. kamelotis arwera: Ria yviteli feris tabletebi (s.f. t. 2. gv. 84-is mixedvit). kamelotis sasualo masa ganvsazrvret awonvis metodit sasualo masa 0,1105g-ia, Teoriuli masidan (0,1100 g) sasualod gadaxrilia +0,45%-iT (norma ± 7,5%). kamelotis identifikaciisa da raodenobrivi gansazrvrisatvis gamoyenebul iqna ultraiisferi speqtrofotometruli metodi: standartuli nimusis xsnars STanTqmis maqsimumi hqonda 364 nm talris sigrzeze, xolo sakvlevi substanciis xsnars STanTqmis maqsimumi hqonda 366 nm talris sigrzeze (norma 365 ± 2nm); kamelotis ert tabletsi (15,0mg) meloqsikamis raodenobrivi Semcveloba iyo mg (norma 13,875-16,125mg).,,kamelotis (15 mg GM Pharmaceuticals, saqartvelo) tabletebisa da misi analogis, preparat movalisis (15 mg UCB, Sveicaria) tabletebis xsnadobis SedarebisTvis gamoviyenet ultraiisferi speqtrofotometruli metodi: meloqsikamis gamotavisuflebis sasualo procentuli raodenoba movalisidan aris - 96,42%. kamelotidan ki 92,96%, movalistan SedarebiT kamelotidan moqmedi nivtierebis gamotavisuflebis gadaxra aris - 3,59% (norma - 5%). 102

103 preparat,,kameloti -Si garese minarevebi ganvsazrvret maralefeqturi sitxuri qromatografiuli analizis gamoyenebit: calkeuli araidentificirebuli minarevis Semcveloba ar unda arematebodes 0,2%-s. mirebuli Sedegebia: 1. (1666,7X X110X1,04)/(550X15X3416,5)=0,00064%; 0,00064%<0.2%; 2. (1666,7X X110X2,66)/(550X15X3416,5)=0,00016%; 0,00016%<0.2%; jamuri minarevebis Semcveloba ar unda aremetebodes 0,5%-s 0,00064%++0,00016%= ; <0.5%. kvlevis Sedegebi. meloqsikamis tabletebis xarisxis kontrolisas gansakutrebuli yuradreba unda mieqces gaxsnis macvenebels, aseve substancias, mza produqtsi minarevebis Semcvelobas da substanciis polimorfizmis sakitxs. preparatis qimiuri bunebidan gamomdinare (enoluri bunebis gamo meloqsikami sakmaod labiluri naertia misi fizikur-qimiuri Tvisebebi icvleba garemoze damokidebulad), medikamentis stabilurobis uzrunvelsayofad, sawiroa igi Senaxul iqnas specifiuri SefuTviT. literatura 1. b. WumburiZe farmacevtuli qimia. Tb.: 2009; b. WumburiZe, m. jorjikia, l. kunwulia, T. CikvilaZe. farmacevtuli qimiis laboratoriuli samusaoebis saxelmzrvanelo. Tb.: 2010; ,,problemuri wamlebi bestseleri 4. Sinha P.K., Jeswani R.M., Topagi K.S., Damle M.C. Road K., Near R.T.O. A validated RP-HPLC method for determination of Meloxicam in the Presence of its Impurities. International Journal of PharmTech Research 2009; 1(4): SUMMARY QUALITY CONTROL AND QUALITY ASSURANCE FOR TABLETS CONTAINING MELOXICAM Tsitsilashvili E., Chikviladze T., Lashauri N., Otarashvili T. Tbilisi State Medical University, Department of Pharmaceutical and Toxicological Chemistry; QA Department of Georgian Pharmaceutical Manufacturing Company - GM Pharmaceutical, Georgia From June of 2014 planned changes are coming in regulations of medicines circulation on Georgian market, more precisely, it s planned to move Non Steroidal Anti Inflammatory drugs from the group of OTC medicines into the group of preparation controlled by prescription. Therefore, special attention will be paid on Quality Control and Quality Assurance issues of these medicines. Because of these facts, with QA department of Georgian Pharmaceutical Manufacturing Company - GM Pharmaceutical, we decided to work out the quality control standards for the medicine,,camelot 15 mg (which is Meloxicam containing drug implemented in production by GMP since 2005). Material for the research included Meloxicam substance, finished product,,camelot 15mg and its analogue medicine,,movalis 15mg. Analytical methods used for this reaseach were the following: Physical analytical methods - for measuring Average Tablet Mass and Dissolution; UV Spectrophotometry - for identification and quantitative measuring of Meloxicam in API (Active Pharmaceutical Ingredient) as well as in finished product, also, for measuring dissolution of finished product,,camelot and for comparision of dissolution results with the same measured for the finished product,,movalis. Infrared Spectrophotometry - was used for the control of polymorphism in API. High performance liquid chromatography (HPLC) - was used for measuring of external impurities in API as well as in finished product. As the conclusion we can outline the fact, that while checking the quality of Meloxicam tablets, special attention should be paid on the dissolution profile of the product. Also, quantity of external impurities should be observed 103

104 very carefully in API as well as in finished product and the issue of polymorphism should be taken into account by all means. As a result of our experiment i twas found that all these parameters were within acceptable limits. As a means of quality assurance of the tablets the need of using special packaging material for insuring the stability of the product should be highlighted. These measures should be taken because of the enolic nature of meloxicam which results in the unstability of the product and its dependence on the environmental conditions. ofloqsacinis Semcveli preparatis kafras mg-iani tabletebis bioveiveruli Seswavla, bioeqvivalentobis kvlevisgan gantavisuflebis miznit 2 b. WumburiZe, 1 S. cxadaze, 1 q. kobaxize, 1 n. lasauri, 2 T. CikvilaZe, 2 n. imnaze 1 farmacevtuli kompania,,ji-em-pi, xarisxis kontrolis laboratoria; 2 Tbilisis saxelmwifo samedicino universiteti, farmacevtuli da toqsikologiuri qimiis departamenti samkurnalo sasualebebis usafrtxoebisa da xarisxis problema sul ufro da ufro met aqtualobas izens msofliosi. farmacevtul bazarze jeneriki preparatebis raodenoba yovelwliurad izrdeba. qartul farmacevtul bazarze jenerikebs daaxloebit 95% ukaviat, Sesabamisad, aqtualuria am samkurnalo sasualebebis efeqturobis Seswavla originalur preparatebtan mimartebasi. jeneriki preparatis moqmedi gansazrvreba mititebulia direqtivasi 2001/83/EC, muxli 10(2)(b) [1]. standartul samkurnalo sasualebastan misi bioeqvivalentoba Sesabamisi kvlevebit aris dadasturebuli. aseve mititebulia, rom bioserwevadobis kvlevebi sawiro ar aris, Tu SegviZlia vacvenot, rom jeneriki samkurnalo sasualeba akmayofilebs bioeqvivalentobis kvlevidan gantavisuflebis Sesabamis kriteriumebs [1-3]. rogorc wesi Sesadarebel preparatad gamoiyeneba originali preparati. farmacevtulad aqtiuri nivtierebebi (Active Pharmaceutical Ingredients (API)) biofarmacevtuli klasifikaciis mixedvit (Biopharmaceutics Classification System (BCS)) iyofa otx jgufad: klasi I marali xsnadoba marali SeRwevadoba klasi II dabali xsnadoba marali SeRwevadoba klasi III marali xsnadoba dabali SeRwevadoba klasi IV dabali xsnadoba dabali SeRwevadoba WHO-is Tanaxmad, farmacevtulad aqtiuri nivtiereba xasiatdeba marali xsnadobit, Tu srulad ixsneba ml-ze nakleb moculobasi, ph diapazonsi, 37±1 ⁰ C (FDA-is mixedvit ph ), xolo miicneva maral SeRwevadad, rodesac Seiwoveba 85% an meti, (FDA-is mixedvit 90% da meti) [1,2]. koncefcia gamoiyeneba farmacevtulad eqvivalenturi, swrafad gamontavisuflebadi, myari peroralurad misarebi dozirebuli formebistvis, romeltac sistemuri moqmedeba axasiatebt da farto Terapiuli indeqsi aqvt. biofarmacevtuli klasifikaciis safuzvelze bioeqivalentobis kvlevebisgan gantavisufleba exeba I da III klass. 104

105 BCS klasifikaciis I klasi: - wamlis substancia xasiatdeba marali xsnadobit da sruli absorbciit; - nacvenebia saanalizo da standartuli produqtis Zalian swrafi (rodesac etiketze mititebuli raodenobis 85%-ze meti 15 wutis farglebsi ixsneba) in vitro xsnadobis maxasiateblebi specialuri motxovnebis gatvaliswinebit; - ar arsebobs ewvi, rom Semavseblebi mnisvnelovan gavlenas axdenen bioserwevadobaze; BCS BCS klasifikaciis klasifikaciis III klasi: - wamlis substancias marali xsnadoba da dabali absorbcia axasiatebs; - nacvenebia saanalizo da standartuli produqtis Zalian swrafi (>85% -ze 15 wutis ganmavlobasi) in vitro xsnadobis maxasiateblebi specialuri motxovnebis gatvaliswinebit; - Semavseblebi Tvisobrivad analogiuria da raodenobrivad Zalian msgavsi [1]. WHO da FDA-is wayenebuli motxovnebi bioveiveruli kvlevistvis: -sami sxvadasxva buferuli xsnari: ph 1.2 (an 0.1 M HCl an SGF enzimebis garese), ph 4.5 da ph 6.8 (an SIF enzimebis garese); (mjavianoba uzrunvelyofili unda iyos mteli eqsperimentis ganmavlobasi); - gamxsneli aris moculoba: ml (500.0 ml EMEA-s mixedvit); - gamxsneli aris temperatura: 37±1 ⁰ C; - TiToeuli aresatvis 12 erteulis gamoyeneba, ertze meti seria, nicbebis brunvis sicqare 75 br/wt, kalatebis _ 100 br/wt; - nimusis arebis rekomendebuli dro: mag., 10, 15, 20, 30, 45 da 60 wt; - Sesadarebeli da originali preparatis xsnadobis profilebi unda iyos msgavsi samive buferul aresi (msgavsebis faqtori f 2 50); - Tu 15 wt-si ixsneba etiketze mititebuli dozis 85% da meti, xsnadobis profilebi SeiZleba msgavsad CaiTvalos monacemta statistikuri damusavebis garese; - preparatidan gamontavisuflebuli nivtierebis variaciis koeficienti 20%-ze naklebi unda iyos pirveli wertilisatvis da 10%-ze naklebi meoredan bolo wertilamde [3]. biofarmacevtuli klasifikaciis I da III klasis wamlis substanciebistvis gamoyenebuli unda iyos satanadod gansazrvruli Semavseblebi ( cder/iig/iigfaqweb.htm) da gatvaliswinebuli unda iyos SesaZlo urtiertqmedebebi, romelic gavlenas axdens wamlis bioserwevadobaze da/an xsnadobis maxasiateblebze. Semavseblebis gavlena I klasis substanciebze nakleb savaraudod miicneva, magram srulad gamoricxuli ar aris [6]. arnisnulidan gamomdinare Cveni kvlevis mizans warmoadgenda: biofarmacevtuli klasifikaciis safuzvelze qartuli farmacevtuli sawarmos GMP-is, ofloqsacinis Semcveli (BCS klasifikaciis Iklasi) preparatis kafras mg-iani tabletebis bioveiveruli Seswavla, bioeqvivalentobis kvlevidan gantavisuflebis miznit. kvlevis masala da metodebi. ofloqsacinis referens - standartuli nimusi (USP, seria: G1I182), qartuli farmacevtuli sawarmo GMP-is mier warmoebuli, ofloqsacinis Semcveli preparatis kafra mg-iani tabletebi (seria: ; ; ; vada: 01/2017) ofloqsacinis Semcveli originali preparatis - tarividis mg-iani tabletebi (safrangeti Aventis Pharma/Hoechst Marion Roussel seria: BS8085; BS8086; BS8087; vada: ). kvlevistvis gamoyenebuli xelsawyoebis - analizuri saswori CPA 225D; ultraiisferi speqtrofotometri Agilent 8453; xsnadobis ganmsazrvreli xelsawyo Erweka DT 826 LH - teqnikuri da saeqspluatacio maxasiateblebi mtlianad Seesabameba ass, britanetis da evropis farmakopeebis motxovnebs da damowmebulia ssip `standartebis, teqnikuri 105

106 reglamentebisa da metrologiis erovnuli saagento~-s mier. eqsperimentuli nawili: ofloqsacinis in vitro xsnadobis gansazrvra preparat kafrasa da originali preparatis - tarividis tabletebsi. vixelmzrvanelet USP 37 NF 32-s farmakopeis statiasi arwerili metodikit are ml 0.1 M HCl xsnari, gaxsnis dro 30 wt, nicabis brunvis sicqare 100 br/wt, ares temperatura 37± C [3]. gansazrvra vawarmoet speqtrofotometrulad ultraiisfer ubansi, λ=294 ±2 nm sigrzis talraze, 1 sm fenis sisqis kiuvetsi. Sesadarebeli xsnari M HCl, standartuli xsnari ofloqsacinis standarti C=0.0088mg/ml. nimusebis areba movaxdinet 5, 10, 15, 20 da 30 wt-iani intervalebit. mirebuli Sedegebis safuzvelze (cxrili 1) agebul iqna gamontavisuflebuli aqtiuri nivtierebis raodenobis drostan damokidebulebis grafiki (nax. 1). cxrili 1. preparat kafras K400.0 mg-iani tabletebis 0.1 M HCl -Si xsnadobis monacemebi xut sxvadasxva wertilsi dro (wt) dasaxeleba, seria kafra mg tab tarividi mg tab კაფრა ტარივიდი nax. 1. kafras K400.0 mg-iani tabletebidan gamontavisuflebuli aqtiuri drostan damokidebulebis grafiki 0.1 M HCl -Si nivtierebis preparat kafrasa da originali preparatis tarividis sxnadoba sam sxvadasxva buferul aresi,xut sxvadasxva drois intervalsi. sakvlevi da originali preparatebis sxvadasxva aresi xsnadobis msgavsebis dasadastureblad, xsnadobis profilis Sedareba movaxdinet original preparattan Semdeg buferul aresi: qloriduli buferuli xsnari (ph 1.2); acetaturi buferuli xsnari (ph 4.5) da fosfaturi buferuli xsnari (ph 6.8). ares moculoba ml, brunvis sicqare 100 br/wt, temperatura 37 C, sinjebis arebis droebi: 5, 10, 15, 20 da 30 wt. xsnadobis mirebuli profilebis Sedarebis Sefaseba movaxdinet msgavsebis koeficientis mesveobit, romlis gansazrvris metodi ariarebulia WHO-isa da FDA-is mier. mirebuli monacemebis (cxrili 2) safuzvelze agebul iqna gamontavisuflebuli aqtiuri nivtierebis raodenobis drostan damokidebulebis grafiki (nax. 2). cxrili 2. preparatebis kafras K400.0 mg-iani da tarividis mg-iani tabletebis 106

107 xsnadobis monacemebi sam buferul aresi xut sxvadasxva wertilsi dro (wt) dasaxeleba, seria ph kafra mg tab. ph tarividi mg tab. ph kafra mg tab. ph- 4.5 tarividi mg tab. ph- kafra mg tab. 4.5 ph- 6.8 tarividi mg tab. ph (%) dro (wt) კაფრა ph-1,2 ტარივიდი ph-1,2 კაფრა ph-4,5 ტარივიდი ph-4,5 კაფრა ph-6,8 ტარივიდი ph-6,8 nax. 2. kafrasa da tarividis xsnadobis profilis Sedareba ph-1.2-ze; ph-4.5-ze; ph- 6.8-ze da 5, 10, 15, 20 da 30 wt-is drois intervalsi kvlevis Sedegebis ganxilva. rogorc cxrili #2-dan Cans 15 wt-si gamotavisuflda etiketze mititebuli dozis 85%-ze meti, rac miutitebs xsnadobis profilis msgavsebaze da arar sawiroebs monacemebis statistikur damusavebas. Npreparatidan gamotavisuflebuli nivtierebis variaciis koeficienti (cxrili 3) 20%-ze naklebia pirveli wertilebisatvis, xolo meore wertilidan bolo wertilamde 10%-ze naklebi, rac akmayofilebs bioveiveruli kvlevisatvis wayenebul motxovnebs [1-3]. cxrili 3. preparatebis kafras K400.0 mg-iani da tarividis mg-iani tabletebis variaciis koeficienti sam buferul aresi xut sxvadasxva wertilsi dro (wt) ph variaciis koeficienti (%) ph ph ph

108 daskvna: WHO da FDA-is mier bioveiveruli kvlevistvis wayenebuli motxovnebis mixedvit Seswavlil iqna qartuli farmacevtuli sawarmos GMP-is mier warmoebuli ofloqsacinis Semcveli preparatis kafras K400.0 mg-iani tabletebi originali preparatis mimart. gansazrvra vawarmoet speqtrofotometrulad ultraiisfer ubansi, λ=294 ±2 nm sigrzis talraze, 1 sm fenis sisqis kiuvetsi. Sesadarebeli xsnari M HCl, standartuli xsnari ofloqsacinis standarti C=0.0088mg/ml. nimusebis areba movaxdinet 5, 10, 15, 20 da 30 wt-iani intervalebit. SeviswavleT preparat kafrasa da originali preparatis tarividis sxnadoba sam sxvadasxva buferul aresi. xsnadobis profilis msgavsebis dasadastureblad, Sedarebis Sefaseba movaxdinet msgavsebis koeficientis mesveobit, romlis gansazrvris metodi ariarebulia WHO-isa da FDA-is mier. bioveiveruli kvlevis Sedegad dadginda, rom qartuli farmacevtuli sawarmos GMP-is mier warmoebuli ofloqsacinis Semcveli preparatis kafras K400.0 mg-iani tabletebs da ofloqsacinis Semcveli originali preparatis tarividis mg-iani tabletebs (mwarmoebeli Aventis Pharma/Hoechst Marion Roussel safrangeti) aqvt msgavsi xsnadobis profili da Sesabamisad SesaZlebelia produqtis gantavisufleba bioeqvivalentobis kvlevisgan. produqtis bioeqvivalentobis kvlevebisgan gantavisuflebas ki udidesi mnisvneloba aqvs, vinaidan mcirdeba is materialuri danaxarjebi, rac dakavsirebulia bioeqvialentobis kvlevastan. Lliteratura 1. Guideline on the investigation of Bioequivalenc (Doc. Ref.:CPMP/EWP/QWP/1401/98 EMEA,2008.) 2. WHO multisource document: Working document QAS/04.109/Rev.1; 3. International Journal of Pharmaceutical & Biological Archives 2012; 3(4): ; Biowaivers: Criteria and Requirements; 4. USP 37 NF 32 official Monographs/Ofloxacin WHO Essential Medicines List, 14 th edition, march 2005 can be found under: who.int/hq/2005/a87017_eng.pdf; 6. reziume ofloqsacinis Semcveli preparatis kafras mg-iani tabletebis bioveiveruli Seswavla, bioeqvivalentobis kvlevisgan gantavisuflebis miznit 2 b. WumburiZe, 1 S. cxadaze, 1 q. kobaxize, 1 n. lasauri, 2 T. CikvilaZe, 2 n. imnaze 1 farmacevtuli kompania,,ji-em-pi, xarisxis kontrolis laboratoria; 2 Tbilisis saxelmwifo samedicino universiteti, farmacevtuli da toqsikologiuri qimiis departamenti samkurnalo sasualebebis usafrtxoebis da xarisxis problema ufro met aqtualobas izens msofliosi. farmacevtul bazarze jeneriki preparatebis raodenoba yovelwliurad izrdeba. qartul farmacevtul bazarze jenerikebs daaxloebit 95% ukaviat, Sesabamisad, mnisvnelovania am samkurnalo sasualebebis efeqturobis Seswavla originalur preparatebtan mimartebasi. WHO da FDA-is mier bioveiveruli kvlevistvis wayenebuli motxovnebis mixedvit 108

109 Seswavlil iqna qartuli farmacevtuli sawarmos GMP-is mier warmoebuli ofloqsacinis Semcveli preparatis kafras K400.0 mg-iani tabletebi da ofloqsacinis Semcveli originali preparatis tarividis mg-iani tabletebi (mwarmoebeli Aventis Pharma/Hoechst Marion Roussel safrangeti). dadginda, rom orive nimusis xsnadobis profili msgavsia da aris originali medikamentis eqvivalenturi. mirebuli Sedegebis safuzvelze SesaZlebelia produqti gantavisuflebul iqnas bioeqvivalentobis kvlevebisgan. SUMMARY OFLOXACIN CONTAINING TABLETS,,KAFRA 400 MG, BIOWAIVER STADYING PROCEDURE ON BASED BCS, ACCORDING TO WHO 2 Chumburidze B., 1 Tskhadadze Sh., 1 Kobakhidze K., 1 Lashauri N., 2 Chikviladze T., 2 Imnadze N. 1 GM Pharmaceuticals Ltd, Quality Control Laboratory; 2 TSMU, Department of Pharmaceutical and Toxicological chemistry Nowadays safety and quality issues of medical products is getting more and more frequent topic for discussion all over the world. Every year boost of generic medicines is observed on a pharmaceutical market. The Georgian Pharmaceutical Market is filled with 95% of generic medicaments, therefore, it s important to study efficacy of generic medicines towards original medicines. According to the WHO and FDA requirements for Biowaiver studies, we conducted analysis for Ofloxacin containing tablets Kafra 400 mg, produced by Georgian pharmaceutical manufacturing company GMP, towards the original medicament Tarivid 400 mg tablets (Manufacturer: Aventis Pharma/Hoechst Marion Roussel, France). It was established that dissolution profile for both of medicaments are similar and equivalent to the original medicine. From the results we can conclude, that it s acceptable to exclude bioequivalence studies from planned trials. DEVELOPMENT AND VALIDATION OF EFFICIENT AND SELECTIVE RP-HPLC METHOD FOR SIMULTANEOUS DETERMINATION OF GUAIFENESIN IMPURITIES IN THE PRESENCE OF GUAIFENESIN, AMBROXOL HYDROCHLORIDE AND SALBUTAMOL SULFATE IN MULTI DRUG COMPONENTS PHARMACEUTICAL FORMULATIONS Melikyan L., Grigoryan R., Topchyan H., Davtyan T. Scientific Center of Drug and Medical Technology Expertise JSC Ministry of Health of Armenia, Komitas 49/4, Yerevan 0051, Republic of Armenia ABSTRACT Purpose. Currently recommend consideration for management of mucus hypersecretion is the combination of expectorants, mucoregulators, mucolytics and bronchodilators in different multi drug components pharmaceutical formulations. Therefore, the simultaneous identification and quantification of active pharmaceutical ingredients and its related impurities along with some other active ingredients and excipients in multicomponent pharmaceutical products is a very intensive activity performed at many levels of the drug discovery pipeline and beyond. 109

110 Methods. The different analytical performance parameters such as linearity, precision, accuracy, limit of detection (LOD), limit of Quantification (LOQ) were determined according to International Conference on Harmonization (ICH) Q2B guidelines. The chromatographic separation was achieved on EC NUCLEODUR-100-3C18 (250x4,6 mm, 5µm packing) column using gradient elution. The mobile phase gradient constituted by 75:20:5 v/v mixture of ammonium acetate buffer: acetonitrile and methanol (solvent A) and 25:60:15 v/v mixture of ammonium acetate buffer: acetonitrile and methanol (solvent B) gave sharp and well defined peaks with significant R T values which were desired for quantification of GFN related impurities in the presence of blank, containing GFN, ambroxol hydrochloride, salbutamol sulfate methyl-, propylparaben and citric acid monohydrate The Ultra Violet spectrophotometric determination was performed at 275 nm. Results. The Linearity of the calibration curves for the analytes in the desired concentration range is good (r2 = 0.999) by High Performance Liquid Chromatography. The LOQ were 1 and 0.1 μg/ml respectively for guaifenesin β-isomer and guaiacol. The average percentage recovery of guaifenesin impurities was found to be within % of range. The developed method can be successfully used for identification and quantification of guaifenesin impurities β-isomer and guaiacol in the presence of guaifenesin, ambroxol hydrochloride and salbutamol sulfate in multi drug components pharmaceutical formulations. Conclusion. A new, accurate and selective HPLC method were developed for the determination of guaifenesin impurities, 2-(2-methoxyphenoxy)-propane-1,3-diol (β-isomer) and 2-methoxyphenol (guaiacol) in the presence of guaifenesin, ambroxol hydrochloride, salbutamol sulfate in multi drug components pharmaceutical formulations as per the ICH guidelines. The methods were found to be simple, selective, precise and accurate. Therefore, these methods can be used as routine testing as well as stability analysis of guaifenesin and ambroxol impurities in bulk and in formulations. zogierti biologiurad aqtiuri nivtiereba saqartvelosi mozardi AMARANTHUS RETROFLEXUS L-is TeslebSi da fotlebsi malania m., sulaqvelize c., kikalisvili b., turabelize d. Tbilisis saxelmwifo samedicino universiteti, iovel qutatelazis farmakoqimiis instituti Amaranthus-is jijlayas gvari (ojaxi Amaranthaceae) fartodaa gavrcelebuli msofliosi. saqartvelosi 9 saxeoba izrdeba. rogorc literaturuli wyaroebidan cnobilia, Amaranthus-is Teslebidan mirebuli zeti amcirebs sisxlsi da RviZlSi qolesterinis dones, xels uwyobs imunuri da hormonaluri sistemebis ardgenas, organizmidan gamoyavs mzime metalta marilebi, gamoiyeneba wylulebis, Wrilobebis, damwvrobis Sesaxorceblad. Cveni kvlevis mizans warmoadgenda saqartvelosi velurad mozardi A. retroflexus L-is TeslebSi da fotlebsi biologiurad aqtiuri nivtierebebis Seswavla. Txelfenovani qromatografiis metodis gamoyenebit A. retroflexus L-is fotlebis spirtian eqstraqtsi dadgenil iqna 11 aminomjava: fenilalanini Rf 0,77; leicini Rf 0,74; metionini Rf 0,69; valini Rf 0,66; alanini Rf 0,58; cisteini Rf 0,55; asparagini Rf 0,50; serini Rf 0,52; prolini Rf 0,43; arginini Rf 0,25; lizini Rf 0,18. A. retroflexus L.-is Teslebidan da fotlebidan mirebul heqsanian jamsi speqtrofotometruli metodis gamoyenebit (talris sigrze 451 nm) gansazrvrul iqna karotinoidebis Semcveloba, romelic Seadgens 4,0-8,0 mg %, xolo fotlebidan da 110

111 Teslebidan mirebul wylian eqstraqtsi vsazrvravdit askorbinis mjavas titraciis metodit saxelmwifo farmakopeis mixedvit, romelic meryeobs 0,2-0,4% farglebsi. aseve dadgenil iqna Amaranthus-is Teslebidan mirebul zetsi bunebrivi ujeri naxsirwyalbadis skvalenis arseboba. A. retroflexus L.-is Teslebidan mirebuli zeti SesaZlebelia mowodebul iqnas, rogorc biologiurad aqtiuri kvebiti danamati, xolo karotinoidebis marali Semcvelobis gamo mcenare SeiZleba gamoyenebul iqnas qacvis zetis msgavsi moqmedebis preparatis misarebad. literatura 1. Тутельян В.А. Применение масла амаранта при сердечно-сосудистых заболеваниях. М.: 2006; Berger А., Gremaud G., Baumgartner M., Rein D., Monnard I. Cholesterol- Lowering Properties of Amaranth Grain and oil in Hamsters Int. J. Vitamin. Nutr. Res. 2003; 73(1): Баранова И. Масло амаранта. Косметология и аромалогия 2006;2: Государственная фармакопея. XI издание. Вып 2; saqartvelosi mozardi AMARANTHUS CRUENTUS L, A.RETROFLEXSUS L, A.BLITOIDES S.WATS Teslebis lipidebi turabelize d., sulaqvelize c., kikalisvili b., malania m. Tbilisis saxelmwifo samedicino universiteti, iovel qutatelazis farmakoqimiis instituti, saqartvelo Amaranthus-is jijlayas gvari (ojaxi Amaranthaceae) fartodaa gavrcelebuli msofliosi, saqartvelosi 9 saxeoba gvxvdeba. Cveni kvlevis mizans warmoadgenda saqartvelosi mozardi Amaranthus -is gvaris 3 saxeobis: A.cruentus L-is, A.retroflexsus L-is da A.blitoides s.watsis Teslebis neitraluri lipidebis, fosfolipidebis, glikolipidebis, aminomjavebis, karotinoidebis, askorbinis mjavas, skvalenis da sxva biologirad aqtiuri nivtierebebis Seswavla, romelebic fartod gamoiyenebian samedicino praqtikasi da warmoadgens ert-ert aqtualur sakitxs medicinasi. bolo wlebsi gansakutrebit didi yuradreba eqceva Amaranthus-is gvaris sxvadasxva saxeobis mcenaris lipidebs, vinaidan mati Teslebidan mirebuli zeti mdidaria biologiurad aqtiuri, sxvadasxva klasis organuli nivtierbebit, cnobilia, rom Amaranthus-is gvaris mcenaris Teslebis zeti Seicavs Semdeg mnisvnelovan biologiurad aqtiur nivtierebebs: tokoferols (vitamini E), riboflavins (vitamini B 2 ), Tiamins (vitamini B 1 ), D jgufis vitaminebs, vitamin-a-s provitamins, cximovan mjavebs, skvalens, aminomjavebs, narvlis mjavebs, fitosterinebs da sxva. dadgenilia, rom Teslebidan mirebuli zeti amcirebs sisxlsi da RviZlSi qolesterinis dones, xels uwyobs imunuri da hormonaluri sistemebis ardgenas,aumjobesebs nivtierebata cvlas, organizmidan gamoyavs radionuklidebi, Slakebi, mzime metalta marilebi, aumjobesebs Tirkmlebis da RviZlis funqciebs, zemoqmedebs kuwisa da nawlavebis lorwovan garsze, aradgens ujredebis da epiteliumis musaobas, xels uwyobs wylulebis, Wrilobebis, damwvrobis Sexorcebas, Trgunavs patogenur mikroorganizmebs, azlierebs samkurnalo efeqts onkologiur TerapiaSi, Cirqovan daavadebebis da sxva SemTxvevebSi. 111

112 mecnierebis ganvitarebis Tanamedrove etapze didi mnisvneloba eniweba lipidsemcveli mcenareebis gamovlenas da gamoyenebas medicinasi, SesaZlo samkurnaloprofilaqtikuri preparatebisa da biologiurad aqtiuri danamatebis (bad) saxit [1-6]. institutsi 1960 wlidan mimdinareobda lipidebis Seswavla fitoqimiur ganyofilebasi [7-9] wlidan institutis reorganizaciis Semdeg Seiqmna lipidebisa da antraqinonebis laboratoria, sadac dremde grzeldeba kvlevebi lipidebis mimartulebit. saqartvelosi kultivirebuli Amaranthus cruentus-is Teslebis heqsanit eqstraqciit vrebulobdit neitraluri lipidebis jams gamosavlit 7 %. neitraluri lipidebis jamsi armocenili iqna Semdegi klasis naertebi: naxsirwyalbadebi, triacilgliceridebi, Tavisufali cximovani mjavebi. dominirebuli klasia triacilgliceridebi. standartuli metodebis gamoyenebit dadgenili iqna A.cruentus-is Teslebidan mirebuli zetis fiziko-qimiuri konstantebi [10]. Tavisufali cximovani mjavebis Seswavlas vaxdendit maralefeqturi sitxuri qromatografiuli metodis gamoyenebit, qromatograf-ptg refraqtometriuli deteqtorit R-401, svetze Sebrunebuli fazis sorbentit C 18 porsili. mozrav fazad gamoiyeneboda: 1. metanoli-wyali (1:2), 2. tetrahidrofurani-acetonitrili-wyali (5:7:9)+0,1% ZmarmJavas xsnari. Sedegebis dasamusaveblad gamoiyeneboda programa,,oasis-740,ris Sedegadac dadgenil iqna Semdegi cximovani mjavebi: laurinis 2,3%, miristinis 4,77%, palmitinis 16,7%, stearinis 3,7%, oleinis 3,7%, linolis 14,2%, linolenis 5,2% da araqinonis 1,42%. neitraluri lipidebis mirebis Semdeg darcenil mcenareuli masidan qloroform-metanolis narevit (2:1) vrebulobdit polaruli lipidebis jams gamosavlit 1,6%. arnisnuli jamis gasuftavebis Semde (heqsanit, qrloroformit, acetonit) vrebulobdit da ormxrivi Txelfenovani qromatografiis metodit vadgendit fosfolipidebis Tvisobriv Semadgenlobas. adsorbentad viyenebdit,,l5/40 markis silikagels, sistemebsi: 1. qloroformi-metanoli-amiaki 25% (60:30:5); 2. qloroformi-metanoli-yinulovani ZmarmJava-wyali (170:25:25:6). qromatogramas vamjravnebdit vaskovskis reaqtivit an iodis ortqlit. fosfolipidebis raodenobriv gansazrvras polaruli lipidebis jamsi vaxdendit araorganuli fosforis mixedvit speqtrofotometruli metodit, talris sigrze 820 nm, ris Sedegadac dadginda fosfolipidebis Semdegi Semcveloba: lizofosfatidilqolini- Rf 0,2-4,9%, fosfatidilinoziti- Rf 0,4-14,4%, fosfatidilqolini-rf 0,57-19,5%, fosfatidiletanolamini- Rf 0,74-29,8%, N-acillizofosfatidileTanolamini-Rf 0,83-7,6%, N-acil fosfatidiletanolamini-rf 0,9-9,7% da araidentificirebuli fosfolipidi 12,9% [11]. saqartvelosi velurad mozardi mcenare A.retroflexus L-is Teslebis lipidebidan heqsanit eqstraqciit vrebulobdit neitraluri lipidebis jams gamosavlit 6,7%. neitraluri lipidebis jamsi armocenilia: naxsirwyalbadebi, triacilgliceridebi, Tavisufali cximovani mjavebi. dominirebuli klasia triacilgliceridebi. standartuli metodebis gamoyenebit dadgenilia A.cruentus-is Teslebidan mirebuli zetis fiziko-qimiuri konstantebi. maralefeqturi sitxuri qromatografiuli metodit dadgenil iqna Semdegi cximovani mjavebi: laurinis 2,5 %, miristinis 4,8 %, palmitinis 18,4%, stearinis 2,8%, oleinis 32%, linolis 21,4%, linolenis 6,1% da araqinonis 2,4%. neitraluri lipidebis mirebis Semdeg darcenili mcenareuli masidan vrebulobdit polaruli lipidebis jams gamosavlit 1,4%. fosfolipidebis Tvisobriv da raodenobriv Semcvelobas vadgendit iseve, rogorc A.cruentus-is SemTxvevaSi. speqtrofotometruli metodit dadginda fosfolipidebis Semdegi Semcveloba: lizofosfatidilqolini-rf 0,19-8,79%, fosfatidilinoziti-rf 0,39-14,35%, fosfatidilqolini- Rf 0,61-24,6%, fosfatidiletanolamini- Rf 0,72-20,37%, N- 112

113 acillizofosfatidiletanolamini-rf 0,81-8,9%, N-acilfosfatidileTanolamini-Rf 0,92-9,5% da araidentificirebuli fosfolipidi 11,4%. saangariso periodsi Seswavlili iqna saqartvelosi velurad mozardi Amaranthus blitoides s.wats Teslebis neitraluri lipidebis jami (nl) gamosavlit 6,1%. neitraluri lipidebis jamsi armocenili iqna Semdegi klasebi: naxsirwyalbadebi, triacilgliceridebi, Tavisufali cximovani mjavebi, sterinebis kvali, dominirebuli klasia triacilgliceridebi. Tavisufali cximovani mjavebis Tvisobrivi da raodenobrivi Semadgenloba dadgenil iqna maralefeqturi sitxuri qromatografiuli metodit. ris Sedegadac identificirebulia Semdegi cximovani mjavebi: laurinis 3,4%, miristinis 3,1%, palmitinis 8,1%, stearinis 15,9%, oleinis 38,9%, linolis 15,7%, linolenis 4,4%, araqinonis 3,6%, begenis 3,1% da araidentificirebuli sav. C24 3.1%. fosfolipidebis jamsi dadgenil iqna fosfolipidebis Semdegi Semcveloba: N- acilfosfatidiletanolamini-rf 0,91; N-acillizofosfatidileTanolamini- Rf 0,81; fosfatidiletanolamini- Rf 0.69; fosfatidilqolini-rf 0.57; fosfatidilinoziti-rf 0,42; lizofosfatidilqolini- Rf 0,2 da araidentificirebuli 3.1%. arnisnul mcenareebsi dadgenilia Tavisufali cximovani mjavebi, fosfolipidebi, naxsirwyalbadebi, tokotrienolebi da sxva. yuradrebas ipyrobs triterpenuli naxsirwyalbadi skvaleni da tokotrienolebi. skvalenis gamoyeneba SesaZlebelia dermatologiasa da kosmetologiasi. cnobilia, rom Amaranthus-is gvaris mcenareebi Seicaven tokoferolebs. isini warmodgenili arian tokotrienolebis saxit,romelta antioqsidanturi aqtivoba gacilebit maralia, vidre vitamini E-s. arnisnul naertebs gaacniat kardioproteqtoruli Tvisebebi, amcireben sisxlzarrvebsi qolesterinis folaqebis warmoqmnas, axasiatebt simsivnis sawinaarmdego moqmedeba. yovelive zemoarnisnulidan gamomdinare isaxeba perspeqtiva arnisnuli nivtierebebis medicinasi gamoyenebis miznit, rogorc biologiurad aqtiuri danamatebis, aseve profilaqtikuri da samkurnalo preparatebis saxit. literatura 1. Шиков А.Н., Макаров В.Г., Рыженков В.Е. Растительные масла и масленные экстракты: технология, стандартизация, свойства. Изд. Дом: «Русский врач»; Адекенов С.М. Новые оригинальные фитопретараты. Перспективы применения в медицине и организация их производства. Конференция «Фармация Казахстана». 2009; 1: Коростелева Ю.А., Офицеров Е.Н. Особенности схем комплексного использования надземных частей Амаранта. Конфер. «Химия и технология растительных веществ». М.: 2006; Офицеров Е.Н. Комплексная переработка семян рестении рода Amarantys L. Вестник биотехнологии и физико-химической биологии 2007; 3(3): Баранова И. Масло амаранта. Косметология и Аромалогия 2006; 2: Амаранта масла Форум Aromarti.ru Pagel-9 ( aromarti.tu/showthreed.php) Кемертелидзе Э.П., Далакишвили Ц.М. Биологически активные липиды некоторых растений, произрастающих в Грузии. Тб.: «Мецниереба»: saqartvelos mecnierebata akademiis i. qutatelazis sax. farmakoqimiis institutis 70 wlis saiubileo gamocema, w. aprili, Далакишвили Ц.М. Химическое изучение биологически активных растительных липидов. Докторская диссертация. Тб.: Кейтс. М. Техника липидологии. М.: Мир; Folch J., Less M., Stoane-Stenlay J.H., J.Z Biol.chem. 113

114 SUMMARY LIPIDS OF SEEDS AMARANTHUS CRUENTUS L, A.RETROFLEXSUS L, A.BLITOIDES S.WATS GROWING IN GEORGIA Turabelidze D., Sulakvelidze Ts., Kikalishvili B., Malania M. Tbilisi State Medical University, Kutateladze of Pharmakochemistry, Georgia There is studied chemical composition of neutral and polar lipids of the seeds of: Amaranthus cruentus L, A.retroflexsus L, A.blitoides s.wats growing in Georgia. The composotion of free fatty acids was determined with help HPLC. There is determined class and fatty acidal composition of them, qualitative and quantitativ determination of phospholipids is carried. ELECTROSPUN NANO- AND MICROFIBERS FROM BIODEGRADABLE POLYMERS AS CONTROLLED RELEASE SYSTEMS FOR ANTIBIOTICS Vynias D., Kikionis S., Ioannou E., Roussis V. University of Athens, School of Pharmacy, Department of Pharmacognosy and Chemistry of Natural Products, Panepistimiopolis Zografou, Athens 15771, Greece Electrospinning is a method for the production of nano- and microfibers exhibiting high surface area, affecting the release rate of incorporated bioactive compounds in comparison to conventional polymeric films. The present study focused on the production of nanofibers from biocompatible polymers as carriers of antibiotics and the evaluation of their release rate. Such membranes could replace the conventional dermal patches offering controlled release of the antibiotic for an extended application period, while at the same time they could reduce the side-effects caused by the administration of high doses of antibiotics. In this context the methodology for the preparation of antibacterial nanofiber membranes modified with a number of antibiotics via electrospinning was developed. Specifically, nanofibers of cellulose acetate incorporating fusidic acid, oxotetracycline and neomycine, as well as nanofibers of polylactic acid with either polycaprolactone and/or cellulose acetate incorporating oxotetracycline were prepared. The morphology of the modified nanofibers was characterized using SEM, the chemical integrity of the incorporated antibiotics was evaluated by NMR and their release rates were measured by UV. Nanofibers of cellulose acetate modified with fusidic acid exhibited chemical stability, as well as the best controlled release rates depending on the concentration of the incorporated antibiotic. 114

115 ARNICA MONTANA VALUABLE MEDICINAL PLANT AND SOME TRAITS OF ITS ESTABLISHMENT INTO CULTURE IN BULGARIA 1 Balabanova V., 2 Vitkova A., 1 Zheleva-Dimitrova D., 1 Gevrenova R. 1 Department of Pharmacognosy, Faculty of Pharmacy, Medical University - Sofia, Dunav str. 2, 1000 Sofia, Bulgaria; 2 Institute of Biodiversity and Ecosystem Research, Bulgarian Academy of Science, Akad. G. Bonchev str., bl. 23, 1113 Sofia, Bulgaria Arnica montana L. (Asteraceae) is a high-valued medicinal plant since it has been used for centuries in the treatment of sprains, bruises, muscle pains and etc. [1]. The plant substance Arnicae flos contains sesquiterpene lactones which are responsible for its anti-inflammation effect and properties [2-5]. During the last decades arnica natural populations are rapidly declining [6,7]. Many countries have trials on its introduction and cultivation, but there are some problems concerning with its acclimatization and adaptation [8-10]. In the period two ex situ collections of Arnica montana were established on Vitosha Mt. and Rhodopi Mt. (Bulgaria). This study presents data on the impact of climate and soil conditions. Тhe morphometric parameters were also described and statistically calculated. The yield on the plants from the studied collections was established and the content of sesquiterpene lactones (STL) was determined by pharmacopoeia method [11]. The results reveal that temperature and moisture are the main abiotic factors which are important for its successful growth. Most of the morphometric parameters were highly variable as a result of plants adaptation to the new areas. The most important signs are diameter of anthodium and number of inflorescence per plant in accordance with Principal Component Analyses (PCA). The yield on Vitosha Mt. and Rhodopi Mt. collections is 141 kg/ha and 268 kg/ha, respectively; the quantity of STL is 1.44% and 1.73%, respectively, and it s high above the requirements according to the European Pharmacopoeia. In conclusion, the study reveals that Arnica montana, an important natural resource, has a good acclimatization in Bulgarian areas and the collected plant material is valuable due to its STL content. REFERENCES 1. Kathe W. In: Medicinal and aromatic plants. Netherlands: 2006; Willuhn G, Rottger PM, Mattheisen U. Helenalin- and 11,13-dihydrohelenalinester from flowers of Arnica montana. Planta Med. 1983; 49(12): Lyss G, Knorre A, Scmidt TJ, Merfort I, Pahl HL. Helenalin, an anti-inflammatory sesquiterpene lactone from Arnica, selectively inhibits transcription factor NF- kappaв. Biol. Chem. 1997; 378 (9): Lyss G, Knorre A, Scmidt TJ, Pahl HL, Merfort I. The anti-inflammatory sesquiterpene lactone helenalin inhibits the transcription factor NF- kв by directly targeting p65. The Journal of Biological Chemistry 1998; 273: Klaas Ch A, Wgner G, Laufer St, Sosa S, Loggia R D, Bomme U, Pahl H L, Merfort I. Studies on the antiinflammatory activity of phytopharmaceuticals prepared from arnica flowers. Planta Medica. 2002; 68(5): Ellenberger A. Assuming responsibility for a protected plant: WELEDA, s endeavour to secure the firm, s supply of Arnica montana. In TRAFFIC Europe (Ed.): Medicinal Plant Trade in Europe: conservation and supply. Proceedings of First International Symposium on the Conservation of Medicinal Plants in Trade in Europe. TRAFFIC Europe, Brussels: 1998; Lange D. Europes medicinal and aromatic plants: their use, trade and conservation. TRAFFIC International, Cambridge: Delabays N., Mange N. Culture of Arnica montana L.: the agronomy and plant protection. Rev. Suisse Vitic Arboric Hortic. 1991; 23(5): Bomme U., Mittermeier M., Regenhardt I. Results to develop a procedure for field-cultivation of Arnica montana L. 1 and 2. Mitteilung. Drogenreport. 1995; 8,12,5-10, 13, Galambosi B. Introduction of Arnica montana L. in Finland. Z. Arzn.Gew. Pfl. 2004; 9(4): European Pharmacopoeia. 7 th ed. Strasburg, Council of Europe (COE) - European Directorate for the Quality of Medicines (EDQM), Strasbourg: Council of Europe: 2011;

116 NOVEL COMPOUNDS FROM HELLEBORUS CAUCASICUS AND THEIR ANTIOXIDANT POTENTIAL 1,2 Muzashvili T., 3 Masullo M., 2 Kowalczyk M., 1 Kemertelidze E., 2 Oleszek W., 2 Stochmal A., 3 Piacente S. 1 Iovel Kutateladze Institute of Pharmacochemistry, 36 P. Sarajishvili st., 0159, Tbilisi, Georgia; 2 Department of Biochemistry and Crop Quality, Institute of Soil Science and Plant Cultivation State Research Institute, ul. Czartoryskich 8, Puławy, Poland; 3 Dipartimento di Farmacia, via Giovanni Paolo II, n. 132, Fisciano, Salerno, Italy Helleborus genus combines about 20 species, distributed in Europe and Asia. Mainly subterranean organs of plant species are used and studied. Various compounds of steroid class, including bufadienolids, furo- and spirostanol glycosides, ecdysteroids are described to date. In recent years phenolic glycoside derivatives and quercetin glycosides have been reported from the aerial parts of some European spp. and an antioxidant activity of polar extracts has been evidenced [1-4]. For the first time Helleborus caucasicus A.Br., a Caucasian endemic species was researched for its phenolic composition and antioxidant activity. Plant leaves were defatted with CHCl 3 in a Soxhlet apparatus and further extracted with 80% MeOH two times at 45 C. After solvent removal, dry residue was suspended in water and passed through a preconditioned short preparative column (6 cm 10 cm, LiChroprep RP-18, µm, Merck), followed by washing with water to remove carbohidrates and 40% MeOH for eluting phenolics. Phenolic fraction was subjected to the column chromatography (LiChroprep RP-18, µm, Millipore Corp., Bedford, MA), washed with distilled water and then with increasing concentration of aqueous methanol (2.5 % increments from 0 % to 100% MeOH). Fractions containing 1-3 major compounds were purified on a 2 cm 50 cm, µm RP-18 glass column using an isocratic system (ACN-1% AcOH) optimized for each one based on the analytical separation. This led to the isolation of 7 individual flavonoides: quercetin-3-o-β-d-xylopyranosyl-(1 2)-O-β-D-galactopyranosyl-7-O-β-Dglucopyranoside (1), kaempferol-3-o-[2-(e-caffeoyl)]-β-d-xylopyranosyl-(1 2)-β-D-galactopyranosyl-7-O-β-Dglucopyranoside (2); quercetin 3-O-[2-(E-caffeoyl)]-β-D-xylopyranosyl-(1 2)-β-D-galactopyranosyl-7-O-β-Dglucopyranoside (3); quercetin-3-o-[2-(coumaroyl)]-β-d-xylopyranosyl-(1 2)-β-D-galactopyranosyl-7-O-β-Dglucopyranoside (4); quercetin-3-o-[3-(e-caffeoyl)]-β-d-xylopyranosyl-(1 2)-β-D-galactopyranosyl-7-O-β-Dglucopy-ramnoside (5); quercetin-3-o-β-d-galactopyranosyl-(3-hydroxy-3-methylglutaroyl)-7-o-β-dglucopyranoside (6) and quercetin-3-o-β-d-xylopyranosyl-(1 2)-β-D-galactopyranoside (7), along with the 3- hydroxyl-2-methyl-4-h-pyran-4-one-3-o-(6-o-caffeoyl)-β-d-glucopyranoside (8) and cholest-7-en-3-one (9). The former six flavonoids are novel for plant kingdom and the latter three compounds (7-9) are reported here for the first time in Helleborus genus. The structures of single compounds were elucidated by spectrometric (ESI-MS) and spectroscopic (UV, NMR) means. All isolated compounds were evaluated for their antioxidant potential using trolox equivalent antioxidant capacity measurement (TEAC) and quercetin-3-0-glucoside as a standard. Compounds 1,3,5 and 6 were found to posses the highest activity. Table 1. In vitro trolox equivalent antioxidant capacity (TEAC) of compounds of Helleborus caucasicus A.Br compound TEAC value (mm ± SD) ± ± ± ± ± ± ± ± ± quercetin 3-O-glucoside ±

117 Acknowledgement. The work was supported by the Seventh Framework Program of European Community, PROFICIENCY (Contract No ). The authors declare no competing financial interest. REFERENCES 1. Braca A, Prieto J.M, Tommasi N.D., Tome F, Morelli I. Furostanol saponins and quercetin glycosides from the leaves of Helleborus viridis L. Phytochemistry 2004; 65: Prieto J.M, Siciliano T, Braca A. A new acylated quercetin glycoside and other secondary metabolites from Helleborus foetidus. Fitoterapia 2006; 77: Vitalini S, Braca A, Fico G. Study on secondary metabolite content of Helleborus niger L. leaves. Fitoterapia 2001; 82: Cakar J, Paric A, Vidic D, Haveric Anja, Haveric S, Maksimovic M, Bajrovic K. Antioxidant and antiproliferative activities of Helleborus odorus Waldst. Et Kit, H. multifidus Vis. and H. hercegovinus Martinis. Natural Product Research 2012; 25: SAPONINS WITH HIGHLY HYDROXYLATED OLEANANE-TYPE AGLYCONES FROM SILPHIUM ASTERISCUS Masullo M., 1 Calabria L., 2 Pizza C., 1 Piacente 1 S. 1 Dipartimento di Farmacia, via Giovanni Paolo II, n 132, Fisciano, Salerno, Italy; 2 The Evergreen State College, 2700 Evergreen Parkway, Olympia, WA Silphium L. (Asteraceae) is a small genus of 12 species common to the prairies and woodlands of central North America [1]. This genus is easily recognized by its perennial habit, large flower heads with yellow ray and disc flowers, typical of the sunflower family. Native American tribes considered Silphium spp. medicinal herbs and prepared extracts of the leaves and flowers for respiratory and kidney ailments and also applied the roots of Silphium spp. as poultice for bleeding wounds, backaches and hemorrhaging [2]. Phytochemical investigations of Silphium spp. have resulted in the isolation of almost all traditional classes of secondary metabolites, including flavonoids and phenolic acids [3], essential oils, sesquiterpenes [4], diterpenes [5], and oleanane-type triterpene saponins [6,7]. Silphium asteriscus L., commonly known as starry rosinweed, is found in prairies, glades, woodlands and savannas of the southeastern United States, its taxonomy is complex and several varieties have been named based on basal rosettes, phyllaries and other differentiating characters [1]. In an effort to further characterize triterpene saponins of medicinal significance from Silphium spp., the chemical investigation of S. asteriscus has been undertaken. The leaf MeOH extract of S. asteriscus was purified by different chromatographic steps to afford new eighteen triterpene saponins. Their structures were elucidated by extensive spectroscopic methods including 1D- ( 1 H and 13 C) and 2D-NMR (DQF-COSY, HSQC, HMBC, and TOCSY) experiments as well as ESIMS analysis. The saponins isolated from S. asteriscus possess oleanane aglycones differently hydroxylated at positions C-3, C-6, C- 16, C-23 and C-29. In particular C-23 appears differently oxidized with the replacement of the methyl group with a primary alcoholic function, an aldehydic function or a carboxylic function. These compounds are characterized by the occurrence of aglycone moieties never reported in literature. 117

118 HOH 2C HO HO O OH O O R 2 HOH 2C O O HO HO OR 3 R 2 R1 HOH 2C HO HO O HOH 2C HO HO O OH O R 3 R1 OR 4 Several studies have demonstrated that polyhydroxylated triterpenes isolated from members of the Asteraceae exhibit potent anti-inflammatory effects, as well as, antitumor and cytotoxic activities [8]. Taking into account the unusual structural features of S. asteriscus saponins to determine their possible functional role as cancer preventives, the cytotoxic activities of the isolated compounds were tested against Hela (human epitheloid cervix carcinoma), Jurkat cells (leukaemic T-cell line) and DLD-1 (colorectal adenocarcinoma). REFERENCES 1. Clevinger J.A. New Combinations in Silphium (Asteracaceae: Heliantheae). Novon 2004; 14: Hamel P.H., Chiltoskey M.U. Cherokee Plants and their Uses: A Four Hundred Year History. Herald Publishing, Co., North Carolina: Williams J.D., Wojcińska M., Calabria L.M., Linse K., Clevinger J.A., Mabry T.J. The flavonoids and phenolic acids of the genus Silphium and their chemosystematic value. Nat Prod Commun. 2009; 4: Bohlmann F., Jakupovic J. Natural terpene derivatives New sesquiterpene hydrocarbons with anomalous carbon skeletons from Silphium species. Phytochemistry 1980; 19: Pcolinski M.J., Doskotch R.W., Lee A.Y., Clardy J. Chlorosilphanol and silphanepoxol, labdane diterpenes from Silphium perfoliatum. J. Nat. Prod. 1994; 57: Davidyants E.S., Putieva Zh.M., Bandyukova V.A., Abubakirov N.K. Triterpene glycosides of Silphium perfoliatum. V. Structure of Silphioside A. Chem. Nat. Compd. 1986; 22: Calabria L.M., Piacente S., Kapusta I., Dharmawardhane S.F., Segarra F.M., Pessiki P.J., Mabry T.J. Triterpene saponins from Silphium radula. Phytochemistry 2008; 69: Neukirch H., D Ambrosio M., Sosa S., Altinier G., Loggia R.D.,Guerriero A., Improved anti-inflammatory activity of three new terpenoids derived, by systematic chemical modification from the abundant triterpenes of the flowery plant Calendula officinalis. Chem. Biodivers. 2005; 2: INTEGRATED MASS SPECTROMETRIC AND MULTIVARIATE DATA ANALYSIS APPROACH FOR THE CLASSIFICATION OF STRAWBERRIES (FRAGARIA ANANASSA) CROPS 1 D Urso G., 2 d Aquino L., 1 Pizza C., 1 Montoro P. 1 Dipartimento di Farmacia, Università degli Studi di Salerno, via Giovanni Paolo II, Fisciano (SA); 2 ENEA, Centro di Ricerche Portici, Piazzale E. Fermi Portici (NA) Strawberry [Fragaria ananassa Duch. (Rosaceae family)] fruits are very popular berries widely consumed, both fresh and as an ingredient in processed products [1]. They are a very rich source of bioactive compounds especially phenolic compounds, which are well known for their antioxidative activities; The main phenolic classes in strawberries are anthocyanins, flavonols, flavanols, hydroxycinnamic derivatives, proanthocyanidins, ellagitannins, and ellagic acid derivates [2]. Due to these bioactive compounds, Strawberry fruits are reported to have antioxidant, anticancer, anti-inflammatory and antineurodegenerative biological properties [3]. Several methods, both chemical and physical, may be used in laboratories for food research and control, mainly to evaluate the quality of the product, authenticity/adulteration, and traceability in the production and marketing 118

119 chain. Besides demand for quality parameters, a very important issue is traceability of some chemical markers of food related to its origin and nutritional quality [4]. In the present study, metabolic changes in secondary metabolites during ripening of strawberry fruits were evaluated, and in particular the differences between fruits from organic or traditional crops. Ripe and unripe fruits of Strawberry (Fragaria ananassa) var. Candonga [purchased from Spanish nurseries], were collected from two different farms: Azienda Agricola Barlotti (Salerno, Italy), who produces strawberry with integrated pest and pathogen management technique and Azienda Agricola Concilio (Salerno, Italy), who produces strawberry with organic farming. Collected fruits were frozen, homogenized and extracted with acidic methanol for one night. Resulting extracts were analyzed by direct introduction mass spectrometry using an instrument with an ion trap analyzer (DI-ESI-IT- MS). The obtained data were organized in a data matrix and processed with Multivariate Data Analysis (MVDA) by using the software SIMCA-P +, after manual normalization. Samples were then analyzed by liquid chromatography coupled to high resolution mass spectrometry using a mass spectrometer equipped with an ESI source and an Orbitrap analyzer (LC-ESI-FT-MS). Chromatograms were evaluated using the free software packages MZmine ( and the resulting metabolomics data were processed using SIMCA-P+ software 12.0 (Umetrics AB, Umea, Sweden). Both the data sets were first analyzed by Principal Component Analysis (PCA) to define homogeneous cluster of samples. These clusters were then used as Y classes in partial least squares discriminant analysis (PLS-DA). Both PCA score and loading plots were generated for the entire dataset to visualize clustering by strawberry fruits. The data were also modelled by partial least squares discriminant analysis (PLS-DA) as a supervised approach to exploring clustering relationship. Moreover these data were used to confirm the MVDA (PCA and PLS-DA), through an approach of untargeted analysis. All the difference between fruits collected from organic crops and from traditional crops were underlined. In addition LC-ESI-FT-MS analysis were useful to a comprehensive characterization of metabolic profiles of strawberries (flavonoids, anthocyans and catechins were identified in extracts). Moreover the approach confirm that PCA and PLS analyses could help with predictive information to classify organic crops and traditional crops. In particular with respect to the similar results obtained for the two different mass spectrometric approaches, the present work underlines as a fingerprint analysis could be used to classify two types of products obtained by different cultivations. REFERENCES 1. Seeram N.P., Lee R., Scheuller H.S., Heber D. Identification of phenolic compounds in strawberries by liquid chromatography electrospray ionization mass spectrometry. Food Chemistry 2006; 97: Josuttis M., Verral S., Stewart D., Kruger E., Gordon J., McDougall. Genetic and environmental effects on tannin composition in strawberry (Fragaria ananassa) cultivars grown in different europian countries. Journal of Agricultural and Food Chemistry 2013; 61: Hannum S.M. Potential impact of strawberry on human health: a review of the science, Critical Reviews in Food Science and Nutrition 2004; 44: Pavlovic A. Chemical composition of two different extracts of berries harvested in Serbia. Journal of Agricultural and Food Chemistry 2013; 61:

120 ROOT IN VITRO CULTURES OF GYPSOPHILA GLOMERATA PALL EX M.B. WITHOUT PHYTOCHORMONES AND SAPONIN ACCUMULATION 1,4 Gevrenova R., 2,4 Galante S., 3,4 Pedone G., 4 Henry M. 1 Department of Pharmacognosy, Faculty of Pharmacy, Medical University - Sofia, 2, Dunav street, 1000 Sofia, Bulgaria; 2 Chemical and Physical Biology, Centro de Investigaciones Biolgicas CSIC, Ramiro de Maeztu 9, Madrid, Spain; 3 Universitá degli studi di Bari. Aldo Moro, Facoltá di Farmacia, Dipartimento Farmaco Chimico, Via Orabona, Bari, Italia; 4 Groupe SUCRES, UMR 7565, CNRS Université de Lorraine, Faculté de Pharmacie, 5, rue Albert Lebrun, BP Nancy Cedex, France Saponins are considered as the major bioactive compounds of the roots in vitro cultures of Gypsophila species [1]. A simple and rapid method of excised root cultures from Gypsophila glomerata Pall ex M.B. was performed, allowing continuous growth without phytohormones. Established on MS medium from solid-grown seedlings, these roots were subcultured for 1 year on solid medium before being transferred in a liquid medium to obtain substantial biomass for saponin content analysis. Significant growth for G. glomerata was achieved after 2 months in liquid medium; biomass reached 3 g DW per explant. The sucrose concentration in culture medium (2 and 4%) did not influence the root growth during the first twenty days of rooting and had only a limited effect on saponin content. After acid hydrolysis of the ethanol-aqueous root extracts, two representative prosaponins of the Gypsophila species, gypsogenin 3-O-glucuronide and quillaic acid 3-O-glucuronide, were purified using solid-phase extraction (SPE), then quantified by reversed-phase high-performance liquid chromatography (RP-HPLC). Quantitative analysis of 59-days-old G. glomerata excised roots revealed a higher content of gypsogenin 3-O-glucuronide, up to 3.32±0.26 mg/g DW, as compared with quillaic acid 3-O-glucuronide ±0.17 mg/g DW. However, after 78 days of cultivation, the saponin production in excised roots slowed down but the gypsogenin 3-O-glucuronide in culture medium was able to enhance up to 4 times and reached 1.11± 0.25 mg/g dry weight. In the present study, we found saponins in both excised roots and culture medium which prove that in vitro cultures can contribute in producing saponins from G. glomerata. It could be suggested that selection of cell lines may be effective for enhancing the saponin production in G. glomerata roots. REFERENCES 1. Gevrenova R., Stancheva T., Voynikov Y., Laurain Mattar D., Henry M. Root in vitro cultures of six Gypsophila species and their saponins contents. Enzyme and Microbial Technology 2010; 47(3): kavkasiis endemuri saxeobis SALVIA GAREJI-is qimiuri komponentebi sarareisvili T., alania m., SalaSvili q., qavtaraze n. Tbilisis saxelmwifo samedicino universiteti, iovel qutatelazis farmakoqimiis instituti Seswavlilia armosavlet saqartvelosi gavrcelebuli garejis salbis - Salvia garedji Troitzk. is (oj. Labiatae) qimiuri Sedgeniloba. mcenaris miwiszeda nawilebi fitoqimiuri analizit flavonoidebis, fenolkarbonmjavebis, depsidebis da kondensirebuli taninebis SemcvelobiT mdidari armocnda. mcenaresi mnisvnelovani raodenobit biosintezdeba agretve di- da triterpenuli bunebis nivtierebebi. 120

121 nedleulis spirt-wyliani, qloroformiani, etilacetatiani, eteriani da acetoniani eqstraqtebidan Sesabamisad mirebuli da indentificirebulia naxsirwyalbadi n- nonakozani, lr. temp C; ursolis da oleanolis mjavata stereoizomeruli narevi, kristaluri formit, ormagi lrobis temperaturit ( ; C); C H 5OH salvigenini-5-hidroqsi-6,7,4' trimetoqsiflavoni, lr.temp C, λ 2 330, 280 nm; 1 H bmr-speqtrsi MeOD-Si, δ (m.w.): 8.02 (d, H 2',6''), 7,17 (d, H 3',5'), 6.90 (s, H 3), 6.75 (s, H-8), 4.02 (s, OCH 3-6), 3.95 (s, OCH 3-7), 3.90 (s, OCH 3-4') ; m.m. 328 (mas-speqtrometriit); rozmarinis mjava C H 5OH (kofeinis da α-oqsihidrokofeinis mjavis eteri), lr. temp C; λ 2 max 325, 287 nm. literaturuli monacemebit igi xasiatdeba antivirusuli, antebis sawinaarmdego da antioqsidanturi aqtivobit [1-5]. gamoyofilia agretve kondensirebuli tanini lr. temp C, [α] D (c 0.09; C H 5OH MeOH-H 2 0, 1:1), ui speqtri, λ 2 max 280 nm, iw speqtri ν max, KBr, sm ¹: (OH ), 2931 (- OCH 3 ), 1604, 1527(aromatuli sistema). mas ar gaacnia γ-pironis C=O jgufistvis damaxasiatebeli STanTqmis zoli; 1 H bmr-speqtrsi (MeOD), δ m.w.: 4.48 (s,h 2,epikateqini), 4,43 (d, H 2 kateqini), (dd, H-4); 5.4 (d,h-6). es nivtierebebi garejis salbidan pirveladaa gamoyofili. dadgenilia garejis salbis fenoluri naertebis antioqsidanturi aqtivoba etilendiaminozmarmjavasa da α-tokoferoltan SedarebiT. literatura 1. Lu Y., Foo L.Y. Polyphenolics of Salvia a review. Phytochemistry 2002; 59(2): Прокопенко С.О., Литвиненко В.И. Биологично активнi сполуки рослин роду шавлия. Фармац. журнал 1980; 6: Mabry T.J., Markham K.R. Thomas M.B. The Sistematic Identification of Flavonoids, New York: Academic Press; 1970: Petersen M., Simmonds M.S.J. Rosmarinic acid. Phytochemistry 2003; 62: Rafation G., Khodagholi F., Farimani M.M., Abraki S.B., Gardaneh M. Increase of autophagy and attenuation of apoptosis by Salvigenin promote survival of SH-SY 5Y cells following treatment with H O. Mol Cell. Biochem. 2012; 371(1-2): SUMMARY CHEMICAL COMPONENTS OF THE CAUCASUS ENDEMIC SALVIA GAREDJI TROITZ Sagareishvili T., Alania M., Shalashvili K., Kavtaradze N. Tbilisi State Medical University, Iovel Kutateladze Institute of Pharmacochemistry, Georgia The chemical containing of Salvia gareji (family Labiatae) widely spread in the east Georgia has been studed. Alcohol/aqueous, chloroform, ethyl acetate, petroleum ether and acetone extracts of S. gareji yielded a hydrocarbon, two triterpenoids and three phenolic compounds. By using physical-chemical analysis methods, UV-, IR-, 1 H NMR- spectroscopy and mass spectrometry following compounds were found :n-nonacosane, ursolic and oleanolic acids in the stereoisomeric forms, salvigenin (5-hydroxy-6,7,4'-trimethoxyflavone), rosmarinic acid (easter of coffeic acid with 3,4-dihydroxyphenil lactic acid) and condesed tannin. This compounds from S. gareji were isolatad at first time and it is established their antioxydant activity. max 121

122 SYNTHESIS OF POTENTIAL BIOACTIVE 3Β-SUBSTITUTED STEROIDAL THIOESTERS FROM TIGOGENINE Barbakadze N., Nadaraia N., Kakhabrishvili M.,Onashvili E. Tbilisi State Medical University Iovel Kutateladze Institute of Pharmacochemistry In order to find potential biologically active compounds new steroidal 3β-thioesters were synthesized. The intermediate products obtained by transformation of tigogenine were used as starting materials. Tigogenine was isolated from plant Yucca gloriosa, introduced in Georgia. The reagent of thioacylation - 1-methyl-2-(4-methylphenyl)thioacylthiopyridinium iodide at first was synthesized (yield 65%) by us by interaction of N-methylpyridinium iodide with intermediate complex obtained from carbon disulfide and p-tolylmagnesium bromide. CH 3 NOH CH 3 NOH HO H 1 H R H 3 C S O H 4 H N(CH 3 ) 2 HO 2 R = N(CH 3 ) 2 3 R = OH H 2,3 H H 3 C S O H 5 H S OH O CH 3 H 3 C O H H + H 3 C O H H S 6 S 7 The reactions of O-thioacylation of steroidal alcohols 1-3 were carried out in dry tetrahydrofuran at C during 24 h in presence of catalytic amount of triethylamine. The main products of thioacylation of 20- hydroximino-5α-pregnenolone 1 and 17β-(N,N-dimethylamino)-5α-androstan-3β-ole 2 were 3β-substituted thioesters 4,5 (yield 62% and 75% after recristallisation) and mono- 6 (yield 4%) and disubstituted 7 (yield 45%) thioesters (after purification on the colomn ) from 5α-androstan-3β,17β-diole 3. The structures of the all novel compounds 4-7 were confirmed by IR, 1 H and 13 C NMR spectrums. 122

123 saqartvelosi gavrcelebuli samkurnalo barambos fotlebis fitoqimiuri Seswavla kupravisvili k., joxaze m., bojaze a.,zardiasvili l., WinWaraZe d. berasvili d. Tbilisis saxelmwifo samedicino universiteti, farmakognoziisa da botanikis departamenti samkurnalo barambo Melissa officinalis L. oj. tucosnebi Lamiaceae, barambos latinuri saxelwodeba warmosdga berznuli sityvidan Melissa - rac nisnavs futkars. zogiert qveyanasi mas Taflis yvaviladac moixsenieben. mcenares aqvs limonis damaxasiatebeli suni, amitom mas limnis pitnasac uwodeben. samkurnalo barambo 2000 welze metia warmatebit gamoiyeneba mravali qveynis xalxur da mecnierul medicinasi. is pirvelad arwera Teofrastem SromaSi Historia plantarum. avicenam TiTqmis 1000 wlis win ( ww) saeqimo mecnierebata kanoni - Si miutita arnisnuli mcenaris samkurnalo Tvisebebze /2 /. samkurnalo barambosatvis, iseve rogorc tucosanta ojaxis sxva mcenareebisatvis biologiurad aqtiur nivtierebata ZiriTad jgufs warmoadgens eterovani zeti, romelic gansakutrebul suns aniwebs mas. meore mnisvnelovani jgufi fenilpropanis nawarmebia - kofeinis, qlorogenis, kumaris, ferulis da sinapis mjava etilis eteris saxit. mat Soris gansakutrebit arsanisnavia rozmarinis mjava, romelic tucosanta ojaxisatvis qemotaqsonomiuri nisania. nedleuli Seicavs agretve flavonoidebs, mtrimlav nivtierebebs, kumarinebs, saponinebs, vitaminebs (B 1, B 2, C) /2,3,6,7/. barambo da misi preparatebi gamoiyeneba rogorc sedaciuri sasualeba nevrozis, taqiaritmiis, arteriuli hipertenziis msubuqi formis dros. gaacniat spazmolizuri, tkivilgamayucebeli, antebissawinaarmdego, antia-lergiuli, antimikrobuli antioqsidanturi da imunomodulatoruli Tvisebebi /2,4/. samkurnalo barambo fartod gamoiyeneba yvela qveynis xalxur da mecnierul medicinasi, mat Soris saqartvelosic. Tumca CvenTvis xelmisawvdom literaturasi ar armocnda informacia saqartvelosi gavrcelebuli samkurnalo barambos fitoqimiuri Seswavlis Sesaxeb, aqedan gamomdinare, Cveni kvlevis mizans Seadgenda saqartvelosi gavrcelebuli barambos fitoqimiuri gamokvleva biologiurad aqtiur nivtierebata zogierti jgufis Semcvelobaze. kvlevis obieqtebi: armosavlet saqartvelosi (qartli, kaxeti da Tbilisis midamoebi) Segrovili samkurnalo barambos fotlebi. kvlevis metodebi: Txelfenovani qromatografia, sitxur qromatogra-fiul masspeqtrometruli (LC- DAD/MS) metodi, maralefeqturi sitxuri qromatografia. kvlevis Sedegebi: Txelfenovani qromatografiit silikagelis Txel fenaze (MERCK), gamxsnelta sistemasi : etilacetati - yinulovani ZmarmJava - WianWvelmJava wyali (100:11:11:26) da qloroformi metanoli (8:2) deteqtori: ui λ = nm gamosamjravnebeli reaqtivi: 2-aminoeTildifenilboratis 1% xsnari, samkurnalo barambos fotlebsi dadginda flavonoidebis da fenolkarbonmjavebis Semcveloba. barambos fotlebis metanolian eqstraqtsi ganxorcielda flavonoidebis da fenolkarbonmjavebis identifikacia sitxur qromatografiul masspeqtrometruli (LC - DAD/MS) metodit, Semdegi MS/MS pirobebit qromatografze: AGILENT TECHNOLOGIES 1290 Infinity AGILENT TECHNOLOGIES 6460 Triple quad LC/MS.: gazis temperatura C, 123

124 gazis dinebis sicqare - 10 ml/ wt., nebulaizeri - 45 ml. kapilari 4000 v. denis Zabva v. fragmentoris Zabva v. koliziuri energia - 35 v. samkurnalo barmbos metanolian gamonawvlilsi identificirebulia: fenolkarbonmjavebi, mat Soris rozmarinis, protokatexis, vanilis galis, kofeinis, ferulis, siringis, qlorogenis da litospermis mjava), flavonoidebi - luteolin 7-0- glikozidi apigenin 7-0-rutenozidi, apigenini, luteolini, kvercetini, akacetini, aseve galokatexini; terpenoiduli SenaerTebi - citrali, neroli da Timoli. rozmarinis mjavis raodenobrivi Semcveloba ganisazrvra maralefeqturi sitxuri qromatografiis metodis gamoyenebit. eqsperimentis Sedegad SerCeulia analizis optimaluri pirobebi: sveti, stacionaruli faza: Zorbax Eclipse plus C18 (100 X 2. 1 mm, 1.8µm) winasveti: UHPLC GUARD Zorbax Eclipse plus C18 (5 X 2. 1 mm, 1.8µm) svetis temperatura: 40 0 C mozravi faza: 0.1 % HCOOH (H 2 O) : 0.1 % HCOOH (CH 3 CN) =50 : 50 (V/V) rejimi: izokratuli mozravi fazis sicqare: 0.6 ml/wt, deteqtoris talris sigrze 210, 280 nm. sakvlevi xsnaris momzadeba: 0.1 g (z.w.) dawvrilmanebul barambos amateben 90 ml 50%- iani etilis spirts. acxeleben mdurare wylis abazanaze ukumacivris daxmarebit 30wTis ganmavlobasi. Semdeg filtraven 100ml tevadobis gamzom kolbsi, filtris qaralds Carecxaven 10ml 50%-iani etilis spirtit, avseben Wdemde imave gamxsnelit /5/. ireben 5 mkl sakvlev da 5 mkl rozmarinis mjavis standartuli nimusis xsnars, axdenen qromatografirebas. rozmarinis mjavas standartuli xsnaris momzadeba: g (z.w.) rozmarinis mjavas standartuli nimuss xsnian 30 ml 50%-ian spirtsi 100 ml tevadobis gazom kolbsi. xsnaris moculoba ayavt Wdemde imave gamxsnelit mtrimlavi-, eqstraqtuli nivtierebebi, tenianoba, saerto nacari, minarevebi (fersecvlili nedlulis nawilebi, mocemuli mcenaris sxva nawilebi, organuli da mineraluri minarevebi) gansazrvrulia saxelmwifo farmakopeis mixedvit /1/. organuli mjavebis gansazrvrisatvis gamoyenebulia askilis nayofebze farmakopeis statiasi organuli mjavebis gansazrvris metodika. Sedegebi mocemulia #1 cxrilsi cxrili # 1 samkurnalo barambos fotlebis saqonelmcodneobiti analizis Sedegebi barambos Segrovebis adgili saerto nacari % tenianoba % eqst. nivtierebebi % organuli mjavebi % mtrimlavi nivtierebebi % rozmarinis mjava % qartli Tbilisi kaxeti daskvna samkurnalo barambos fitoqimiuri gamokvlevis Sedegad: metanolian gamonawvlilsi identificirebulia 9 fenolkarbonmjava, flavonoiduri glikozidebi, flavonoidebis aglikonebi da terpenoiduli SenaerTebi. Seswavlilia da dadgenilia mtrimlavi nivtierebebis (12%) organuli mjavebis (4,7%) da rozmarinis mjavas (2%) raodenobiti Semcveloba. dadgenilia nedleulis ketilxarisxovnebis sxva macveneblebic (tenianoba 8.4%, saerto nacari 6.1%, eqstraqtuli nivtierebebi 29.6%). 124

125 mirebuli Sedegebis safuzvelze SesaZlebelia davaskvnat, rom saqartvelosi gavrcelebuli samkurnalo barambo akmayofilebs evropis farmakopeis motxovnebs. literatura 1. saxelwifo farmakopea tomi # 1-2, Tbilisi 1998, 2003w. 2. Зузук Б. М. Мелисса лекарственная (MelіssaoffіcіnalіsL.):Аналитический обзор / Б.М. Зузук, Р.В. Куцик // Провизор С Попова Н.В. Рослини родини ясноткові як джерелакавової та розмаринової кислот та їх похідних / Попова Н.В., Литвиненко В.І., Певнева О.І. // Фармацевтичнийчасопис С Рябинина Е.И. Cравнение химико-аналитических методов определения танидов и антиоксидантной активностирастительного сырья / Е.И. Рябинина, Е.Е. Зотова, Е.Н. Ветрова [и др.] // Аналитика и контроль Т. 15, 2. С European pharmacopoeia Melissa Leaf V.7, 2011, p Evaluation of phenolic acid derivatives and essential oil content in some Melissa officinalis L. varieties / I. Oniga, L. Vlase, A. Toiu [et al.] // Farmacia Vol. 58, 6 P Rosmarіnіc acіd an іmportant phenolіc actіve compound of lemon balm (Melіssa offіcіnalіs L.) / J. Toth, M. Mrlіanova, D. Tekelova [et al.] // Acta Facult. Pharm. Unіv. Comenіanae Vol. 50. P reziume saqartvelosi gavrcelebuli samkurnalo barambos fotlebis fitoqimiuri Seswavla kupravisvili k., joxaze m., bojaze a., zardiasvili l., WinWaraZe d. berasvili d. samkurnalo barambo fartod gamoiyeneba yvela qveynis xalxur da mecnierul medicinasi, mat Soris saqartvelosic. Tumca saqartvelosi gavrcelebuli samkurnalo barambo naklebad Seswavlilia, aqedan gamomdinare Cveni kvlevis mizans Seadgenda saqartvelosi gavrcelebuli barambos fitoqimiuri gamokvleva biologiurad aqtiur nivtierebata zogierti jgufis Semcvelobaze. qromatografiuli metodebis gamoyenebit samkurnalo barambos (Melissa officinalis L.) metanolian gamonawvlilsi identificirebulia 9 fenolkarbonmjava: rozmarinis, protokatexis, vanilis, galis, kofeinis, ferulis, siringis, qlorogenis da litospermis mjava; flavonoiduri glikozidebi: apigenin-7-0-rutenozidi, luteolin-7-0- glikozidi; flavonoidebis aglikonebi: apigenini, luteolini, kvercetini, akacetini, aseve galokatexini; terpenoiduli SenaerTebi: citrali, neroli da Timoli. dadgenilia mtrimlavi nivtierebebis (12%) organuli mjavebis (4.7%) da rozmarinis mjavas (2%) raodenobiti Semcveloba. aseve dadginda nedleulis ketilxarisxovnebis sxva macveneblebic (tenianoba 8.4%, saerto nacari 6.1%, eqstraqtuli nivtierebebi 29.6%). saqartvelosi gavrcelebuli samkurnalo barambo akmayofilebs evropis farmakopeis motxovnebs. SUMMARY PHYTOCHEMICAL STUDY OF LEMON BALM (MELISSA OFFICINALIS L.) LEAVES GROWING IN GEORGIA K Kupravishvili K., Jokhadze M., Bozhadze A., Zardiashvili L., Chincharadze D. Berashvili D. Tbilisi State Medical University Iovel Kutateladze Institute of Pharmacochemistry, Georgia, Lemon balm (Melissa officinalis L.) is a perennial herb in the mint family - Lamiaceae, native to south-central Europe and the Mediterranean region. The goal of the study was phytochemical research of Lemon balm growing in Georgia. By phytochemical study nine phenolcarboxylic acides has been separeted from the methanolic extract of Lemon balm: rosmarinic, protocatechuic, vanillic, gallic, caffeic, ferulic, syringic, chlorogenic and lithospermic acids. Flavonoid glycosides: apigenin-7-0-rutinoside, luteolin-7-0-glucoside; Flavonoid aglycones apigenin, 125

126 luteolin, quercetin, acacetin, gallocatechin; Terpenoids: citral, nerol and thymol. Has been determined quantification of tannins (12%), organic acids (4.7%) and rosmarinic acid (2%). Phytochemical study showed that Lemon balm leaves growing in Georgia is in accordance with european pharmacopoeia. mcenareuli radioproteqtorebis gamoyenebis perspeqtivebi i. gvilava, T. sanikize, m. giorgobiani, b.zurasvili Tbilisis saxelmwifo samedicino universiteti, saqartvelo bolo 30 wlis ganmavlobasi samedicino miznebit (sadiagnostiko da samkurnalo) maionebeli gamosxivebis gamoyenebis done 6 jer gaizarda. maionebeli radiacia intensiurad gamoiyeneba sxivur TerapiaSi simsivnuri da arasimsivnuri procesebis mkurnalobis dros [2,7]. arsanisnavia, rom radioterapia da radiodiagnostika, birtvuli terorizmisa da atomur eleqtrosadgurebze katastrofata mzardi riski dakavsirebulia janmrteli qsovilebis dasxivebastan da radioinducirebuli gartulebebis ganvitarebastan. cocxal organizmsi qsovilebis radiaciuli dasxiveba mimdinareobs ZiriTadad araspecifikuri meqanizmebis mesveobit, romlebic vlindeba sxva saxis dazianebebis (fizikuri da qimiuri) drosac. cocxal qsovilsi gavrcelebisas maionebeli radiacia Jangbadis reaqciuli naertebis lavisebur warmoqmnas ganapirobebs. Teoriuli gatvlebis Tanaxmad, klinikasi gamoyenebuli ertjeradi dozebi (1-2 gr) sawyis periodsi (10-13 wm) ainducirebs superoqsidradikalebis O 2 - da mati dismutaciis produqtis, wyalbadis zejangis (H 2 O 2 ) umnisvnelo raodenobit warmoqmnas. dasxivebis gviani efeqtebi ganpirobebulia pirveladi Jangbadis reaqciuli naertebis oqsidaciuri procesebis jawvur reaqciebsi CarTviT. subujreduli organelebidan oqsidaciuri dazianebis mimart gasakutrebit mgrznobiarea mitoqondriebi. Mmaionebeli radiaciis usualo zemoqmedebis Sedegad qsovilebis Txevad fazebsi warmoqmnili Jangbadis reaqciuli naertebi zemoqmedebas axdens mitoqondriebis metabolizmze (pirveladi efeqtebi), iwvevs mitoqondriul membranebsi tranziciuri forebis gaxsnas, rac uzrunvelyofs mitoqondriul matriqssi Ca 2+ -is ionebis SeRwevas, mitoqondriuli NO-sinTazas (mtnos) aqtivacias da azotis Jangis (NO) gazlierebul warmoqmnas. Aam meqanizmebis sasualebit dasxivebul qsovilebsi Zlieri nitrogen-oqsigenuri stresi inicirdeba. dadgenilia, rom qsovilsi radioinducirebuli dazianebis xarisxi damokidebulia ara mxolod radiaciis dozaze, aramed postradiaciuli oqsidaciuri stresis intensivobaze [6] da endogenuri antioqsidanturi sistemis aqtivobaze [3]. mnisvnelovania am SemTxvevaSi iseti antioqsidanturi bunebis radioproteqtorebis SerCeva, romlebic Seamcireben oqsidaciuri stresis intensivobas da am gzit uzrunvelyofen organizmis postradiaciuli efeqtebisagan dacvas. miuxedavad mravali kvlevebisa, romelic Catarebulia janmrteli qsovilebis radioproteqciis mimartulebit, sagrznobi warmatebebi am dargsi jerjerobit mirweuli ar aris [2]. dreisatvis arsebuli sintezirebuli radioproteqtorebi dabali efeqturobit da/an marali toqsikurobit xasiatdebian [1,7,8]. alternatiuli, ufro metad efeqturi, naklebad toqsikuri da iafi radioproteqtorebis Zieba Tanamedrove samedicino radiologiis mnisvnelovan problemas warmoadgens. bolo 15 wlis ganmavlobasi mecnierebis yuradrebas ipyrobs antioqsidanturi Tvisebebis mqone 126

127 naturaluri naertebi (propolisis eqstraqti, sxvadasxva mcenareuli produqtebi citrusebis hesperidini, Cais polifenoluri naertebi, witeli yurznis eqstraqti da a.s.) [4,5], romlebsac SeswevT ujredebis dacvis unari radioinducirebuli efeqtebisagan. mcenareuli naertebis radioproteqtoruli aqtivoba ganpirobebulia matsi bioaqtiuri antioqsidanturi, imunomodulatoruli aqtivobis mqone nivtierebebis marali SemcvelobiT. literatura 1. Aaron P Brown, Eun Joo Chung, Mary Ellen Urick, William P Shield, III, Anastasia L Sowers, Angela Thetford, Uma T Shankavaram, James B Mitchell, and Deborah E Citrin. Evaluation of the fullerene compound DF-1 as a radiation protector. Radiat Oncol. 2010; 5: Dörr W. Radiation effect in normal tissue - principles of damage and protection Nuklearmedizin. 2010; 49. 1:S El-Assaad W, Kozhaya L, Araysi S, Panjarian S, Bitar FF, Baz E, El-Sabban ME, Dbaibo GS. Ceramide and glutathione define two independently regulated pathways of cell death initiated by p53 in Molt-4 leukaemia cells. Biochem J Dec 15;376(Pt 3): Guo S, Hu Y, Liu P, Wang Y, Guo D, Wang D, Liao H. Protective activity of different concentration of tea polyphenols and its major compound EGCG against whole body irradiation-induced injury in mice. Zhongguo Zhong Yao Za Zhi May;35(10): Hosseinimehr SJ, Mahmoudzadeh A, Ahmadi A, Mohamadifar S, Akhlaghpoor S. Radioprotective effects of hesperidin against genotoxicity induced by gamma-irradiation in human lymphocytes. Mutagenesis May;24(3): Lyng FM, Seymour CB, Mothersill C. Oxidative stress in cells exposed to low levels of ionizing radiation. Biochem Soc Trans May;29(Pt 2): Mettler FA Jr, Brenner D, Coleman CN, Kaminski JM, Kennedy AR, Wagner LK.. Can radiation risks to patients be reduced without reducing radiation exposure? The status of chemical radioprotectants. AJR Am J Roentgenol. 2011, 196(3): Montoro A., J. F. Barquinero, M. Almonacid, A. Montoro, N. Sebastià, G. Verdú, V. Sahuquillo,1 J. Serrano,5 M. Saiz,5 J. I. Villaescusa,1 and J. M. Soriano. Concentration-Dependent Protection by Ethanol Extract of Propolis against γ-ray-induced Chromosome Damage in Human Blood Lymphocytes Evid Based Complement Alternat Med. 2011; 2011: reziume mcenareuli radioproteqtorebis gamoyenebis perspeqtivebi i. gvilava, T. sanikize, m. giorgobiani, b.zurasvili Tbilisis saxelmwifo samedicino universiteti, saqartvelo radioterapia da radiodiagnostika, birtvuli terorizmisa da atomur eleqtrosadgurebze katastrofata mzardi riski dakavsirebulia normaluri janmrteli qsovilebis dasxivebastan da radioinducirebuli gartulebebis ganvitarebastan.cocxal organizmsi qsovilebis radiaciuli dasxiveba mimdinareobs ZiriTadad araspecifikuri meqanizmebis mesveobit, romlebic vlindeba sxva saxis dazianebebis (fizikuri da qimiuri) drosac. cocxal qsovilsi gavrcelebisas maionebeli radiacia Jangbadis reaqciuli naertebis lavisebur warmoqmnas ganapirobebs.dadgenilia, rom qsovilsi radiacia-inducirebuli dazianebis xarisxi damokidebulia ara mxolod radiaciis dozaze, aramed postradiaciuli oqsidaciuri stresis intensivobaze da endogenuri antioqsidanturi sistemis aqtivobaze. mnisvnelovania iseti antioqsidanturi bunebis radioproteqtorebis SerCeba, romlebic Seamcireben oqsidaciuri stresis intensivobas da am gzit uzrunvelyofen organizmis postradiaciuli efeqtebisagan dacvas. 127

128 SUMMARY USING PERSPECTIVES OF PLANT ORIGIN RADIOPROTECTORS Gvilava I., Sanikidze T., Giorgobiani M., Zurashvili B Tbilisi State Medical University, Georgia Radio diagnostic and radiotherapy, nuclear terrorism and nuclear power disaster associated with an increased risk for the development of normal healthy tissue irradiation induced complications. Tissues irradiation in living organism mostly develops by non-specific mechanisms, which are manifested in series of physical and chemicalinjuries. Dissemination of ionizing radiation on living tissue leads to the formation of reactive oxygen species. The level of radiation - induced damage of tissue depends not only on the radiation dose, but also on intensity of post-radiation oxidative stress and activity of endogenous antioxidant system. Selection of effective antioxidant radio protectors, which would reduce the intensity of oxidative stress in the body and thus provide protection from irradiation effects, is very important. profesiuli medicinis ganvitrebis etapebi saqartvelosi xawapurize n., cimakurize m., zurasvili d., cimakurize m., maisuraze e. Tbilisis saxelmwifo samedicino universiteti, saqartvelo profesiuli medicina wamroadgens swavlebas profesiuli riskebis da matgan gamowveuli janmrtelobis efeqtebis Sesaxeb. samecniero teqnikuri progresis Tanamedrove done ganapirobebs umarlesi samedicino ganatlebis sistemis mier zogadi profilis eqimis momzadebisas farto profesiul codnas da momzadebis maral xarisxs. mecnierebisa da teqnologiebis mirwevebit ganpirobebuli mrewvelobisa da soflis meurneobis swraf zrdaganvitarebastan ertad icvleba profesiuli medicina, Tumca ucvleli rceba mizez-sedegobrivi kavsiris Seswavla profesiuli riskebsa da matgan ganvitarebul patologiebs Soris. janmrtelobis mdgomareobaze Sromis mavne pirobebis uaryofit gavlenaze calkeuli cnobebi jer kidev C.w. (VI-VII s.) egviptur damwerlobasi, Zveli saberznetis da romaeli mwerlebis (aristotele, hipokrate, ovidiusi, lukreciusi, galena, aletarqe da sxv) nawarmoebebsi moipoveba. aristoteles da lukreciusis nawarmoebebsi arwerilia vercxlis da oqros sabadoebis mararoelta Soris mzime daavadebebi, ovidiusi da aletarqe metalurgebis Sromis mzime pirobebit gamowveul naadrev sikvdilianobaze weren. specialuri Sromebi janmrtelobis warmoebiti efeqtebis Sesaxeb mxolod XVI saukunidan daiwera, rodesac Tavi icina mrewvelobis ganvitarebam. kerzod, 1556 wels germanelma eqimma da metalurgma agrikolam gamoaqveyna Tavisi nasromi `samto saqmisa da metalurgiis Sesaxeb~, romelsic mtvris SesunTqvis Sedegad mararoelta Soris ganvitrebuli mzime profesiuli daavadebebi arwera wels arorzinebis xanis eqimisa da qimikosis paracelsis wignsi `mtis Wleqis da mtis sxva daavadebebis Sesaxeb~ arwerili iqna mararoelta daavadebebi: cxelebit, qosinit, xvelita da wonasi 128

129 klebit. manve yuradreba miaqcia Sromis mzime pirobebit da xsiri avadmyofobit gamowveul mararoelta sicocxlis xanmokleobas. TviT paracelsis naadrev sikvdilsac istorikosebi ukavsireben mis musaobas tirolis samto metalurgiul warmoebasi. XVII saukunesi gamoqveynda Sromebi (martin ponsi da Semdgom Stokhauzeni) romelsic arwerili iyo mararos musebis da litonis dnobaze momusaveta daavadebebi, mat Soris, tyviit mosxamvis SemTxvevebi. miuxedavad yovelive amisa, pirveli nasromi, romelsic arwerilia sxvadasxva profesiit dasaqmebul pirta Sromis pirobebis sakitxebis sistematizirebuli arwera aris `profesiuli medicinis mamis~, cnobili italieli eqimisa da mecnieris - bernando samacinis mier 1700 wels gamoqveynebuli wigni `xelosanta daavadebebis Sesaxeb~. es wigni im drois codnis enciklopedias warmoadgens da metyvelebs imaze, rom msxvili mrewvelobis ganvitarebis periodma musebsi gazarda astologiuri efeqtebi. fartodaa arwerili mesaxteebis, qimikosebis, mewisqvileebis, mebatqaseebis, abresumis da Tambaqos warmoebis musebis da sxva mravali profesiis xelosanta daavadebebi. profesiuli medicinisadmi mizrvnili pirveli rusuli wigni aris 1847 wels gamocemuli eqim a. nikitinis mier `musebis daavadebebi da matgan dasacavi RonisZiebebis mititebit~. pirveli specializirebuli dawesebuleba am dargsi daarsda 1910 wels italiasi (milani). msoflio profesiuli medicinis samsaxuris mwyobri sistemis Camoyalibeba daemtxva XX saukunes, gansakutrebit mis meore naxevars, rodesac swrafi da mzardi progresi ganicada mrewvelobam (gansakutrebit qimiurma) da soflis meurnoebam wels v. obuxonis iniciativit Camoyalibda profesiul daavadebata Semswavleli instituti, romelsac satavesi Caudga gelmani. amjamad, es instituti cnobilia Sromis medicinis s/k institutis saxelwodebit. yofil sabwota kavsiris teritoriaze propatologiuri klinikebi Camoyalibda yvelgan, sadac funqcionirebda samedicino institutebi da amave saxelwodebit katedrebi, agretve, samedicino sanitaruli nawilebi wels germaniidan dabrunebulma cnobilma qartvelma Terapevtma da sazogado morvawem nikoloz maxvilazem TbilisSi daaarsa saqartvelos musebisatvis pirveli poliklinika, romlis funqciebi imdenad mravalferovani armocnda, rom ukve 1927 wels gadaketda samecniero kvlevit institutad. misi direqtori sicocxlis bolomde brzandeboda b-ni n. maxvilaze, xolo misi gardacvalebis Semdeg instituts mieniwa misi saxeli. am institutis bazaze dremde funqcionirebs Tssu-s garemos janmrtelobis da profesiuli medicinis departamenti. profesiuli medicinis pirvel ganyofilebas xelmzrvanelobs klinicisti mariam (maka) macabeli - pirveli profesori profesiul medicinasi. q-ni salome yifiani, romelmac Seqmna qartvel profesionalta skola arnisnul dargsi, misma armzrdelebma Seqmnes mimartulebebi profesiul medicinasi da pirvelad, msofliosi, Seiswavles da daadgines regionaluri riskebi da janmrtelobis efeqtebi, romlebic saqartvelos samrewvelo obieqtebsa da soflis meurneobasi dasaqmebulebsi SeiZleba ganvitardes. q-n m. macabelis mier msofliosi pirvelad arweril iqna andezitozi pirvelad ariwera da prof. astologuri diagnozi daisva prof. s. yifianis mier. me-20 saukunis 50-ian wlebsi samecniero Sromebi miezrvna manqanizms prof. xavtasis mier [2]. 129

130 profesiuli medicinis ganvitrebasi, aseve, didi Rvawli miuzrvit q-n e. grzelizes, q-n m. weretels, q-n r. manjavizes, q-n f. labazes, q-n n. lomtatizes, q-n a. CageliSvils da sxva mraval sasiqadulo specialists. prof. v. saakazis xelmzrvanelobit Catarebuli kvlevebit Camoyalibda profesiuli alergologiis dargi. dadginda saqartvelosi alergozebis gavrcelebis surati, nozologiuri formebis speqtri, specifikuri da sadiagnostiko kompleqsebi, pirvelad msofliosi ariwera manganumis mier gamowveuli profesiuli bronquli astma (v. saakaze) (3) SemuSavda da praqtikul saqmianobasi gamoiyeneba sxvadasxva sawarmoo alergiit gamowveuli profesiuli astmis specifikuri diagnostika da mkurnaloba. dadginda saqartvelos samxareo patologiis abresumismieri bronquli astma (n. lomtatize, b. RviniaSvili) (5) da imunologiuri Taviseburebani, patologiis riskfaqtorebi da janmrtelobis efeqtebi Tambaqos warmoebasi (m. wereteli, r. TaTabaZe), samtamadno mrewvelobasi dasaqmebulta astologia (r. javaxize, n. ruxaze). manganumismieri patologiis gamomwvevi riskebi da adreuli diagnostikis aspeqtebi (a. xavtasi, r. javaxize, d. zurasvili, n. xawapurize, m cimakurize) [1]. saamseneblo mrewvelobasi Sromis medicinis Taviseburebebi (r. kverencxilaze) saqartvelos qimiur mrewvelobasi dasaqmebulta Sromis pirobebi da samrewvelo patologia (l. baqraze, maia cimakurize, r. kverencxilaze) [4]. aseve msofliosi pirvelad Catarebulia kvleva qartul nacionaluri da klasikuri baletis mocekvaveta Sromis pirobebis da janmrtelobis mdgomareobis Sesaxeb (m. kvaracxelia). mnisvnelovania profesor m. yurasvilis wvlili Sromis higienis ganvitarebasi. mis mier Seswavlilia saqartvelos mrewvelobisa da soflis meurneobis wamyvani dargebis obieqtebis musata Sromis pirobebi, ris safuzvelzec SemuSavebuli da praqtikasi danergilia gamajansarebel RonisZiebaTa kompleqsebi. mas gansakutrebuli wvlili miuzrvis samrewvelo mikroklimatis SeswavlaSi, mis mier mowodebulia cxeli profesiis musata organizmis gadaxurebisagan dacvis mnisvnelovani RonisZieba wylis smis racionaluri rejimi adgilobrivi produqtis mwvane baixis Cais vitaminebit gamdidrebuli nayenis gamoyenebit. mis kalams ekutvnis 200-mde samecniero Sroma; gamocemuli aqvs Sromis higienis metoduri saxelmzrvanelo praqtikuli mecadineobistvis 1989 w. ganvitarebis yvela etapze profesiul medicinasi nebismieri arsebiti daskvna da am daskvnis Sesabamisi RonisZiebebi eyrdnoba profesiuli riskebis Rrmad Seswavlas, rac TavisTavad gulisxmobs seriozul kvlevebs Sromis fiziologiasi, samrewvelo toqsikologiasi da sxva mimartulebebsi. amastan samecniero teqnikuri progresis mirwevebis danergva warmoebasi gulisxmobs axali profesiuli riskebis Seqmnas da axali janmrtelobis efeqtebis ganvitarebas, rac TavisTavad qmnis gamowvevebs, romelta gadawyveta moitxovs Tanamedrove teqnologiebis gamoyenebas kvlevebsi. literatura 1. zurasvili d. qimiuri nivtierebebit gamowveuli nervuli sistemis profesiuli patologiis Taviseburebani konf. `qimiurad sufta garemo janmrteli Taobebi~. masalebi. Tb.: macabeli m. adamianis organizmze marganecis gavlenis sakitxisatvis. n. maxvilazis Sr. higienis da prof. daavadebata s/k institutis Sromebi 1948; t. II. 3. saakaze v. profesiuli daavadebebi. Tbilisi gamomcemloba: `zekari~; kverencxilaze r. Sromis higiena. Tbilisis saxelmwifo samedicino universiteti: Ломтатидзе И. Професиональные аллергические заболевания от воздеиствия натурального щелка (специфическая диагностика и лечение). Авторефю дисс канд. мёед. наук. Тб.: Саакадзе В,П. Степанов С.Л. Профессиональная бронхиальная астма. Саратов изд. ун-та;

131 reziume profesiuli medicinis ganvitrebis etapebi saqartvelosi xawapurize n., cimakurize marina, zurasvili d., cimakurize maia, maisuraze e. Tbilisis saxelmwifo samedicino universiteti, saqartvelo saqartvelos axali socialur-ekonomikuri pirobebi, sakutrebis formis Secvla, mcire sawarmoebis gacena, mozraoba sabazro urtiertobebisken, sazogadoebis demokratizacia da saxalxo meurneobis martvis decentralizacia, mosaxleobis sayoveltao dazrvevis SemoReba-yovelive es gvkarnaxobs momusaveta socialuri dacvis axali formebis danergvasa da msromelta samedicino daxmarebis sistemis srulyofas da evropul standartebze orientirebas. etikis da deontologiis problemebi farmaciasi n. nemsiwverize, v. eriasvili, T. WumburiZe, n. durasvili, n. kvijinaze, s. marularia Tbilisis saxelmwifo samedicino universitetis socialuri da klinikuri farmaciis departamenti, saqartvelo meoce saukunis meore naxevridan samedicino da farmacevtuli etikis ganvitarebaze udidesi zegavlena moaxdina samecniero-teqnikurma revoluciam medicinasi. swored am periods ukavsirdeba rig qveynebsi axali etikuri kodeqsebis Seqmna. Mmsoflios samedicino asociaciam 1948 wels Camoayaliba Jenevis deklaracia romelic hipokrates ficis Tanamedrove variants warmoadgens, xolo 1949 wels Seiqmna ufro detaluri samedicino etikis saertasoriso kodeqsi [1,5].. samedicino da farmacevtuli etika mudmivad ganaxlebadi dargia, vinaidan is realurad arsebul zneobriv aspeqtebs ganixilavs, kerzod urtiertobas pacienttan, dapirispirebis savaraudo mizezebs, savaraudo konfliqtebs. yuradreba etmoba avadmyofis zneobriv, etikur poziciasac. Tanamedrove pacienti ufro aqtiuria, meti pasuxismgeblobit ekideba Tavis janmrtelobas, Sesabamisad, met yuradrebas itxovs eqimisa da farmacevtisagan. xsirad xdeba ori terminis deontologiisa da etikis areva. Ddeontologia aris pasuxismgebloba, valdebuleba sxva adamianis, Cvens SemTxvevaSi pacientis, mimart. Aanu, deontologiis safuzveli aris samedicino etika, xolo TviT deontologia gulisxmobs samedicino etikis principebis praqtikul gamoyenebas [3]. termini deontologia sataves irebs berznuli sityvidan deon (movaleoba),,logos (Seswavla). antebuli santeli aris simboluri emblema, romelic medikosis profesiul qcevas asaxavs. deontologiis ZiriTadi kitxvebia: ra aris Cemi moraluri movaleoba? ra aris Cemi moraluri valdebuleba? rogor avwono erti moraluri valdebuleba meores mimart? situaciidan gamomdinare samedicino profesiis warmomadgeneli 6 ZiriTadi principit sargeblobs: gulisxmiereba, upirvelesad ara avno, avtonomiuroba, samartlianoba, Rirseba, simartle da patiosneba. 131

132 Tumca, amjamad, es principebi xsirad winaarmdegobrivia, rasac mivyavart etikur dilemamde. magalitad: cocxali donoridan Tirkmlis transplantaciis dros eqimi arrvevs princips- ara avno, Tumca mizani humanuria [3,5]. erterti mwvave gansjis sagania reklama. samedicino xasiatis gamocemebsi, samecniero forumebze, masmediis sasualebit eqimebi da farmacevtebi uzadoni unda iyvnen etikuri TvalsazrisiT. isini unda awvdidnen mxolod mecnierulad dasabutebul praqtikul informacias, romelic ar Seicavs reklamas an TviTreklamas. Aam gansazrvrebaze dayrdnobit, etika aris codnis sakitxi, masin, rodesac morali ukve qmedebis safuzvelia [2]. samedicino da farmacevtul etikas saerto fesvebi aqvs. Ffarmacevtuli etika pirveli farmacevtis arsebobistanave gacnda. etika yoveltvis iqneba farmacevtuli praqtikis ganuyofeli nawili. etikuri principebi: pirovnebis pativiscema, informirebuli Tanxmoba da konfidencialoba, aris ZiriTadi pacienttan urtiertobasi. mecnieruli da teqnologiuri siaxleebi gamudmebit iwveven davas socialur Rirebulebebis etikur sakitxebsi. Ffarmacevti valdebulia: - uzrunvelyos profesionaluri konfidencialoba pacientis mkurnalobastan dakavsirebit; - gauwios pacients kvalificiuri momsaxureba, Tavisi kompetenciis farglebsi, mudmivad izrunos profesiuli codnis da ostatobis amarlebaze; - monawileoba miiros saganmanatleblo programebsi; - iyos Tavaziani kolegebtan da pacientebtan urtiertobasi, mimartuli profesiis prestijisa da reputaciis amarlebisaken [2]. rogorc ukve arvnisnet, farmacevtuli deontologiis ert-erti mtavari sakitxia urtiertoba farmacevtsa da pacients (momxmarebels) Soris, gasatvaliswinebelia Semdegi motxovnebi: farmacevtma yuradreba unda miaqcios garegnul, vizualur mxares, rata daimsaxuros pacientis ndoba, gamoamjravnos mis mimart gulisxmiereba, miaqcios yuradreba sakutar mimikasa da Jestebs, radgan pacientebi Zalze mgrznobiareni arian, vicit, rom xsirad sityvac kurnavs adamians. farmacevtmaaar unda daabnios pacienti samedicino terminebit, auxsnas martivad, xandazmulebs gaumeoros ramdenjerme, msvidad da aurelveblad. aucilebelia viqoniot motmineba da movusminot mat, avuxsnat damajerebeli tonit, Secdomis SemTxvevaSi movubodisot [4]. saxelmwifo politika samkurnalo sasualebebis mimoqcevis sferosi itvaliswinebs mosaxleobis uzrunvelyofas efeqtiani, usafrtxo marali xarisxis, xelmisawvdomi samkurnalo sasualebebit; samecniero kvlevis mxardaweras; axali teqnologiebis Seqmnasa da danergvas; samkurnalwamlo sasualebebis warmoebis Semdgom ganvitarebas; amastanave, saxelmwifo afinansebs prioritetul miznobriv programebs, xels uwyobs samkurnalo sasualebebis faswarmoqmnis regulirebas, kompensaciebis sistemas da sxva ekonomikur da samartlebriv RonisZiebebs. farmacevtis valia Tavis saqmianobasi ixelmzrvanelos farmacevtuli kanonebita da kanonqvemdebare aqtebit, instruqciebit, dausvebelia samkurnalo sasualebebis realizacia xarisxis damadasturebeli sertifikatis garese, samkurnalo sasualebebis sacalo realizacias axorcielebs mxolod aftiaqi an misi filiali; saqartvelos teritoriaze mimoqcevasi arsebul wamals Tan unda axldes instruqcia qartul enaze. samkurnalo sasualebebs gascems mxolod satanado licenziis mqone farmacevtuli dawesebuleba. receptis formebs, mat Soris, mkacri arricxvis formebs mati gamoweris wess, ureceptod gasacemi wamlebis nusxas SeimuSavebs da amtkicebs saqartvelos Sromis janmrtelobis da socialuri dacvis saministro. arsanisnavia, rom arnisnuli normativebis darrveva scdeba etika-deontologiis zrvars da isjeba kanonmdeblobit. 132

133 saqartvelosi Tanamedrove, etikuri farmacevtuli bazris Seqmnis xelsewyoba mnisvnelovani amocanaa, arnisna farmacevtuli kompaniebis warmomadgenelta asociaciis armasrulebelma direqtorma i. margvelasvilma misi azrit etikuri, Ria farmacevtuli bazris Seqmna saertasoriso standartebtan da motxovnebtan srul SesabamisobaSi unda iqnes moyvanili, Aam etapze mtavari farmacevtul bazarze etikuri dacvis kontrolis ganxorcielebaa, man arnisna, rom adgilobriv farmacevtul bazarze irrveva medicinis musakis da momxmareblis ufleba, xdeba saaftiaqo qselis personalis araetikuri waxaliseba. Mmomxmarebels eqimis danisnulebas ucvlian da ufro dabalxarisxian an dabalfasian analogs Tavazoben, amit zaraldeba momxmarebeli da saewvo xdeba eqimis reputacia. jandacvis msoflio organizaciis statistikuri monacemebit msofliosi yovelwliurad wamlismieri gartulebebit irupeba adamiani. amastan dakavsirebit sul ufro meti yuradreba eqceva wamlit gamowveuli gartulebebis martvis, aseve wamlis efeqturobis, usafrtxoebis, xarisxis da xelmisawvdomobis problemebs. janmo-s monacemebit sasualod avadmyofi Rebulobs 4-dan 12-mde sxvadasxva medikaments. klinikasi wamlismieri gartulebebi vlindeba33% -Si, xolo ambulatoriul avadmyofebsi 52%-Si [6,7]. AgansakuTrebuli roli SeiZleba Seasrulos klinikurma farmacevtma mkurnal eqimtan ertad, rata Tavidan iqnes acilebuli farmakologiuri SeuTavsebloba, wamlis gverditi efeqtebi da sxva mosalodneli gartulebebi. amave dros klinikuri farmacevti da eqimi Tavis saqmianobasi itvaliswinebs etikis da deontologiis principebs, ramac minimumamde unda daiyvanos profesiuli undobloba da interprofesionaluri gaugebroba, rac samwuxarod, mnisvnelovan etikur problemas warmoadgens. literatura 1. v. eriasvili. socialuri farmacia. Tb.: v. maxaraze. farmaciis menejmenti. Tb.: b. mamulasvili. samedicino etika. Tb.: n. nemsiwverize. farmacevtuli saqminobis menejmenti. Tb.: saqartvelos farmacevtta asociaciis wesdeba/farmacevtis etikuri kodeqsi. farmacevtis fici. Tb.: http// reziume etikis da deontologiis problemebi farmaciasi n. nemsiwverize, v. eriasvili, T. WumburiZe, n. durasvili, n. kvijinaze, s. marularia Tbilisis saxelmwifo samedicino universitetis socialuri da klinikuri farmaciis departamenti, saqartvelo samedicino da farmacevtuli etika da deontologia mudmivad ganaxlebadi dargia. vinaidan is ganixilavs realurad arsebul zneobriv aspeqtebs, kerzod urtiertobas pacienttan da kolegebtan, mati dapirispirebis savaraudo mizezebsa da konfliqtebs. sayuradreboa avadmyofis zneobriv-etikuri poziciac. Tanamedrove pacienti ufro aqtiuria, ufro meti pasuxismgeblobit ekideba Tavis janmrtelobas, Sesabamisad met yuradrebas itxovs eqimisa da farmacevtisagan. etika yoveltvis iqneba praqtikis ganuyofeli nawili. etikuri principebi, rogoricaa, pirovnebis pativiscema, informirebuli Tanxmoba da konfidencialoba, aris ZiriTadi pacienttan urtiertobasi. farmacevtuli deontologiis ert-erti mtavari sakitxia urtiertoba farmacevtsa da pacients (momxmarebels) Soris. farmacevtma yuradreba unda miaqcios garegnul, vizualur mxares,rata daimsaxuros pacientis ndoba, gamoamjravnos 133

134 gulisxmiereba mis mimart, miaqcios yuradreba sakutar mimikas da Jestebs, vicit, rom xsirad sityvac kurnavs adamians. ar unda daabnios pacienti samedicino terminebit, auxsnas garkvevit. Aucilebelia viqoniot motmineba da movusminot mat, avuxsnat damajerebeli tonit, ar ganvsajot. janmo-s monacemebit sasualod avadmyofi Rebulobs 4-dan 12-mde sxvadasxva medikaments. klinikasi wamlismieri gartulebebi vlindeba33%, xolo ambulatoriul avadmyofebsi 52%. gansakutrebuli roli aset SemTxvevaSi SeiZleba Seasrulos klinikurma farmacevtma mkurnal eqimtan ertad, rata Tavidan iqnes acilebuli farmakologiuri SeuTavsebloba, wamlis gverditi efeqtebi da sxva mosalodneli gartulebebi. amave dros klinikuri farmacevtis da eqimis TanamSromloba, itvaliswinebs etikis da deontologiis principebis dacvas, romelic minimumamde daiyvans profesiul undoblobas da interprofesionalur gaugebrobas mat Soris, rac samwuxarod mnisvnelovan etikur problemas warmoadgens. SUMMARY ISSUES OF PHARMACEUTICAL ETHICS AND DEONTOLOGY Nemsitsveridze N., Eriashvili V., Chumburidze T., Dugashvili N., Kvizhinadze N., Magularia S. Tbilisi State Medical University, Department of Sociologic and Clinical Pharmacy, Georgia Medical ethics together with the pharmaceutical ethics are constantly updating fields as it considers really existed moral aspects, in particular, relationship with the patient, presumable causes of conflicts and alleged conflicts. Attention is paid to the patient's moral and ethical position as well. Modern patient is more active and more responsible for his health, consequently asking for more attention from the physicians or pharmacists side.medical and pharmaceutical ethics have common roots.pharmaceutical Ethics appeared at appearing of the first pharmacist.ethics will always be an integral part of pharmaceutical practice. Ethical principles such as respect for persons, informed consent and confidentiality, are considered as major issues in relationship with the patient. As it was noted above, one of the key issues the pharmaceutical deontology is relationship between a pharmacist and a patient (customer), so, the following requirements should be foreseen:pharmacists should pay attention to the appearance, the visual side, to gain the patient's confidence, to express compassion towards him/her, pay attention to their expressions and gestures, as the patients are very sensitive, pharmacists should be very polite and know that even a word often cures They should: not confuse the patient with complicated medical terms, explain clearly, tell the elderly several times and calmly. It is necessary to be patient and listen to them, explain them in a forceful, do not argue and apologize in case of error. According to the data of WHO, in average, a patient receives 4-12 different medications. Drug complications are revealed in 33% of clinical patients and 52% in ambulatory patients, respectively. In this case together with the physician a special role might be given to clinical pharmacist in order to avoid pharmacological incompatibility, adverse drug effects and other possible complications. At the same time, collaboration between clinical pharmacist and physician will minimize inter-professional mistrust and misunderstanding between doctor and pharmacist that is considered as a major ethical problem at modern stage. farmacevtis saqmianobis aspeqtebi farmacevtul dawesebulebebsi durasvili n., eriasvili v., kvijinaze n., nemsiwverize n., WumburiZe T. Tbilisis saxelmwifo samedicino universiteti, socialuri da klinikuri farmaciis departamenti, saqartvelo Cvens qveyanasi jandacvis sistemis ganvitarebis Tanamedrove tendenciebma ganapiroba farmacevtul seqtorsi mnisvnelovani cvlilebebis gatarebis aucilebloba. farmacia - ert-erti yvelaze dinamiurad ganvitarebadi dargia, romelsac udidesi mnisvneloba 134

135 eniweba mosaxleobis janmrtelobis uzrunvelyofis sferosi, romlis warmatebulad funqcionirebisatvis sxvadasxva profilis specialistia sawiro. mat Sorisaa farmacevti adamiani, romelsac usualo kontaqti aqvs pacienttan. gamomdinare musaobis specifikidan, es farmacevtuli infrastruqturis yvelaze mnisvnelovani da rtuli rgolia wels saertasoriso farmacevtulma asociaciam miiro farmacevtta saertasoriso etikuri kodeqsi, romlis safuzvelzec sxvadasxva qveynebis mier SemuSavebul iqna farmacevtis saqmianobis normebi. Tanamedrove saertasoriso etikuri kodeqsi Sedgeba ori nawilisagan: profesiuli da korporaciuli, romelic gansazrvravs farmacevtis qcevis wesebs farmacevtul dawesebulebebsi. kodeqsi moicavs farmacevtis principebsa da qcevis normebis ertobliobas, romelic uzrunvelyofs mosaxleobis droul daxmarebas xelmiswvdomi, maralefeqturi, uvnebeli da xarisxiani medikamentebit [4] wels msoflio jandacvis ansambleam miiro rezolucia farmacevtis rolis Sesaxeb. aqedan gamomdinare, jandacvis msoflio organizaciiis mier SemuSavebuli iqna programa - farmacevtis, rogorc samedicino momsaxurebis eqspertis codnis garrmaveba, romelic cvlis farmacevtis rols momsaxurebis sferosi. cvlilebebis mizans warmoadgens farmacevtuli profesiuli TviTSegnebis axleburi gaazreba [1]. ekonomikurad ganvitarebuli qveynebis gamocdileba adasturebs, rom farmacevtuli saqmianobis ganvitarebis Tanamedrove pirobebsi aucilebelia maralkvalificiuri specialistis arseboba, romelsacuunda SeeZlos miukerzoebeli da kvlevebze damyarebuli rekomendaciebis gacema preparatebtan da mat sworad gamoyenebastan dakavsirebit.l efeqturi farmacevtuli daxmarebis uzrunvelsayofad, mnisvnelovania, rom mudmivad xdebodes farmacevtis profesiuli ganvitareba da informireba samkurnalo sasualebebis Sesaxeb, vinaidan msoflio mastabit izrdeba ureceptod gasacemi medikamentebis CamonaTvali [2]. mkurnalobis usafrtxoebisa da wamlis gamoyenebis racionaluri gzebis misarwevad farmacevtta saertasoriso organizacia, jandacvis sferos sxva specialistebtan ertad, mimartavs xarisxis sertificirebis saertasoriso standartebis SemuSavebas, SeTavazebas da danergvas. saertasoriso standartebi uzrunvelyofen: satanado farmacevtul momsaxurebasa da farmacevtuli produqciis aucilebel maxasiateblebs-xarisxs, efeqturobas, sandoobas, ekologiur sisuftaves da amastan ertad axdenen farmakoekonomikur maxasiateblebit Sefasebas. saertasoriso standartebis gatvaliswinebit farmacevtul dawesebulebebs SeuZliaT pacientebs SesTavazon efeqturi farmacevtuli momsaxureba, romelic sayoveltaod ariarebul motxovnebs akmayofilebs. saertasoriso standartebis danergvisas udidesi mnisvneloba eniweba sam ZiriTad faqtors: - ZiriTadi mizani-pacientis kmayofilebis macveneblis amarleba; - dagegmva, moqmedeba gegmis mixedvit, Sedegebis kontroli da gaumjobeseba; - dokumentireba imisa, rac ketdeba da ketdeba ise, rogorc dokumentirebulia [3]. saertasoriso standartebis safuzvelze, farmacevtuli organizaciebi qmnian Tanamdebobriv instruqciebs, sadac gansazrvrulia farmacevtis funqciuri uflebamovaleobebi; dadgenilia farmacevtuli saqmianobis efeqturd warmartvisatvis motxovnebi savaldebulo ganatlebasa da gamocdilebaze: 135

136 - farmacevtis FmTavari funqcia momxmarebelze orientirebuli saqmianobamaralkvalificiuri momsaxureba, pirveladi samedicino daxmareba da konsultirebaa; - farmacevts unda SeeZlos pacients ganumartos wamlis instruqcia-misi gamoyenebisa da SezRudvebis Sesaxeb.; - aftiaqsi Seqmnas pacientisadmi ketilganwyobili da komfortuli garemo. arnisnuli saqmianobis ganxorcielebasi unda gamoiyenos profesiuli etikisa da deontologiiis sakitxebi; - musaobis processi uzrunvelyos sanitarul-higienur normebi samusao magidastan da zogadad aftiaqsi, amavdroulad daicvas mercandaizingis principebi; - farmacevti valdebulia mkacrad daicvas da ganaxorcielos aftiaqis menejeris mititebebi. izrunos aftiaqis efeqturobasa da mogebis zrdaze; - yoveldriuri samusaos dawyebis win gaecnos axal informacias; - imusaos sacalo realizaciaze, gasces receptit da ureceptod gasacemi medikamentebi, parafarmacevtul saqoneli, amavdroulad daitvalos da gaakontrolos gacemuli farmacevtuli produqtis nasti; - awarmoos motxovnadi saaftiaqo saqonlis arricxvis Jurnali. uzrunvelyos samkurnalo sasualebebis, parafarmacevtuli saqonelis mattvis gankutvnil adgilas (moxmarebis instruqciis gatvaliswinebit, speckontrols daqvemdebarebuli medikamentebi, a siis preparatebi, Termolabiluri medikamentebi) gantavseba; - farmacevti valdebulia gaecnos axali medikamentebis instruqcias da regularulad daeswros saswavlo jgufis leqcia-seminarebs. warmatebit gaiaros sakvalifikacio testireba da mirebuli codna aqtiurad gamoiyenos pacientebtan urtiertobebis sakitxebsi; - sawiroebis SemTxvevaSi valdebulia pacients gauwios pirveladi eqimamdeli momsaxureba; - evaleba konfliqturi situaciis prevencia, xolo rodesac sadao sakitxebi mis kompetencias scdeba, mimartos pasuxismgebel pirs-menejers. pacientze orientirebuli farmacevtuli saqmianobis sworad warmartvisatvis jandacvis msoflio organizaciis da farmacevtta saertasoriso federaciis mier 2000 wels SemoTavazebuli iqna farmacevtis 7 varskvlavi, 7 Tviseba, romelic gansazrvravs farmacevtis profesiul maxasiateblebs [2] farmacevti mzrunveli gadawyvetilebis mimrebi farmacevti moswavle maswavlebeli farmacevti Suamavali menejeri lideri sqema. farmacvetis profesiuli maxasiateblebi farmacevtta saertasoriso federaciam 2006 wels farmacevtis Svidvarskvlavian koncefcias daumata damatebiti funqcia: farmacevti mkvlevari, romelsac samkurnalo sasualebebis racionalurad gamoyenebis sferosi SeuZlia samedicino faqtebze dayrdnobili obieqturi informaciis gamoyeneba. rogorc mkvlevars, farmacevts SeuZlia didi daxmareba armoucinos jandacvis sistemis specialistebs wamalze informaciis miwodebis mxriv. literatura 1. eriasvili v. socialuri farmacia. Tb.: saqartvelos farmacevtta asociaciis wesdeba Karin Wiedenmayer, Rob S. Summers, Clare A. Mackie, Andries G.S. Gous, Marthe Everard. Developing pharmacy practice -A focus on patient care. Dick Tromp index/iso-in-action/health.htm. 136

137 reziume farmacevtis saqmianobis aspeqtebi farmacevtul dawesebulebebsi durasvili n., eriasvili v., kvijinaze n., nemsiwverize n., WumburiZe T. Tbilisis sax. samedicino universiteti, socialuri da klinikuri farmaciis departamenti, saqartvelo Cvens qveyanasi jandacvis sistemis ganvitarebis Tanamedrove tendenciebma ganapiroba farmacevtul seqtorsi mnisvnelovani cvlilebebis gatarebis aucilebloba. farmacia - ert-erti yvelaze dinamiurad ganvitarebadi dargia, romelsac udidesi mnisvneloba eniweba mosaxleobis janmrtelobis uzrunvelyofis sferosi, romlis warmatebulad funqcionirebisatvis sxvadasxva profilis specialistia sawiro. mat Sorisaa farmacevti adamiani, romelsac usualo kontaqti aqvs pacienttan. gamomdinare musaobis specifikidan, es farmacevtuli infrastruqturis yvelaze mnisvnelovani da rtuli rgolia. jandacvis msoflio organizaciis mier SemuSavebulia axali programa- farmacevtis, rogorc samedicino momsaxurebis eqspertis codnis garrmaveba, romelic cvlis farmacevtis rols. cvlilebebis mizezs warmoadgens farmacevtuli TviTSegnebis axleburi gaazreba. farmacevtuli saqmianobis warmartvisas mnisvnelovani gaxda farmacevti flobdes adamianebtan urtiertobis unarcvevebs, fsiqologias da sociologias, iyos adamianze da mis zrunvaze orientirebuli. sakmaod aqtualuria dainergos farmacevtis saqmianobis wesebis Tanamedrove aspeqtebi farmacevtul dawesebulebebsi. SUMMARY A PHARMACOLOGICAL ASPECTS OF PHARMACY INSTITUTIONS Dugashvili N., Eriashvili V., Kvizhinadze N., Nemsitsveridze N., Chumburidze T. Tbilisi State Medical University, Department of Social and Clinical Pharmacy, Georgia The modern tendency of public health reforms in our country caused the necessity of important changes in pharmacy sector. Pharmacy is the dinamyc developing field, and has significant meaning in the providing of the population health, which need the existance of different profile specialists. Pharmacist is among them the human, who has direct contact with patient. Due to the specifics of pharmaceutical activity, this is the main and difficult cyrcle of the pharmaceutical infrustructure. World Health Organization (WHO) implemented new program - Pharmacist as a health care expert to increase the knowledge, which changes the role of pharmacist. The reason of changes is new vision of pharmacy aknowlegment. To manage the pharmacy activity the important thing for pharmacist is to obtain the communication skills, must have a knowledge of scychology and sociology, to be oriented on the patient and care of human. The modern aspects of pharmacological activity is actual in the pharmaceutical institutions. 137

138 HOW CAN PHARMACY ASSISTANTS PLAY A GREATER ROLE IN PUBLIC HEALTH PROGRAMS IN COMMUNITY PHARMACIES Kvizhinadze N., Dugashvili N., Nemsitsveridze N., Chumburidze T. Tbilisi State Medical University, Department of Social and Clinical Pharmacy, Georgia Pharmaceutical technician, is a health care worker who performspharmacy related functions, generally working under the direct supervision of a licensed pharmacist. Pharmacy technicians work in a variety of locations, usually in community/retail and hospital pharmacies but also sometimes in long-term care facilities, pharmaceutical manufacturers, third-party insurance companies, computer software companies, or in government or teaching. Job duties include dispensing prescription drugs and other medical devices to patients and instructing on their use. They may also perform administrative duties in pharmaceutical practice, such as reviewing prescription requests with doctor's offices and insurance companies to ensure correct medications are provided and payment is received. In recent times, they also speak directly with the patients on the phone to aid in the awareness of taking medications on time Little is known about the engagement of pharmacy assistants (PA) in public health service provision. Study was done at the University of Arizona. Used materials are taken from the college of pharmacy and library of the Arizona University Material and methods. To explore the experiences of PA participating in a study to determine whether a cash reward, offered to consumers and pharmacy businesses, increased participation in community pharmacy. PA experience of the study education and training package, participant recruitment and conducting screening were evaluated using knowledge assessment, a questionnaire and focus groups. Results and their discussion. Twenty PA participated in the study: 15 (75%) completed all education and training components, 20 (100%) completed the questionnaire and 10 (50%) attended a focus group. PA rated all education and training components as effective (mean visual analog scale scores >8.5). Most PA (13/18, 72.2%) did not support/were unsure about continuing the program, citing the 25% repeat testing rate (presumed to relate to the cash reward) and privacy/confidentiality issues as reasons. Qualitative analysis suggested that minimizing repeat testing, improved workload management and recognition of, and remuneration for, education and training would make this model more acceptable to PA. Conclusion Findings from this study support the assertion that PA can play a significant role in public health initiatives. It s known that Pharmacy technicians are an essential part of the healthcare field and work in a wide variety of locations including retail/hospital pharmacies, insurance companies and long term care facilities. As a pharmacy technician, you will assist the pharmacist in dispensing medications, keeping inventory and tracking orders, counseling patients on drug usage and many other administrative tasks that make you an indispensable member of the support staff. REFERENCES Anderson C. Community pharmacy health promotion activity in England: A survey of policy and practice. Health Educ J 1996;55: Ramesh A, Nagavi BG, Ramanath KV. A critical review of community pharmacies (Drug stores) in Mysore city. Indian J Hosp Pharm. 2000;37: Bissell P, Traulsen JM, editors. Sociology and pharmacy practice. Manchester, U.K: Pharmaceutical Press;

139 GS-MS DETERMINATION OF COCAINE AND CODEINE IN INTERNAL ORGANS AT THEIR SIMULTANEOUS PRESENCE 1 Yatsynyk A., 2 Bidnychenko Y. 1 Lviv Regional Bureau of Forensic-Medical Investigation, Ukraine, Pekarska str., 61; 2 Lviv National Medical University, Ukraine, Pekarska str., 69 Examination of narcotics and psychotropic poisoning accounts for nearly half of all medicines intoxications research conducted in forensic-chemical laboratories in the Ukraine. Among them is quite common poisoning by multiple toxicologically important substances. Cocaine and codeine are the objects of forensic-chemical investigation in cases of sudden deaths. We tried to detect these drugs in internal organs of unknown person, who died in an ambulance. Material and methods. Unknown poison was isolated from internal organs (liver and kidneys) by infusion with acidified water (oxalic acid to ph 3). Obtained extract was treated with ammonia solution to ph 10 and mixed with chloroform to extract investigated toxic substances. The chloroform extract was concentrated by evaporation in hot air stream. Chemical tests and thin-layer chromatographic (TLC) screening of part of the chloroform extract indicated presence of tropane alcaloids and probably opiates. Extraction residue was dried and resolved in 1 ml of methanol. Methanol solution was purified on Oasis HLB cartridges and used for gas chromatographic investigation. Chromatographic separation was provided on instrument Agilent 6890 with MS detector 5975B on capillary column HP-1 (30 m 250 m 0.25 m of 100 % dimethyl-polysiloxane). Helium flow rate was 1.0 ml/min. Oven temperature programming: 60 ºC 2 min, rate 20 ºC/min to 300 ºC, 300 ºC 10 min. MS parameters: quadrupole temperature 150 ºC, ion source temperature 230 ºC, positive ionization mode with total ions scanning in range m/z, ionization energy 70 ev. Supposed substance were detected on mass-spectra libraries the NIST and the Wiley. Cocaine and codeine were identified and confirmed on retention time and mass-spectra as compared with European Pharmacopoeia reference standards. Results and discussion. In examined internal organs were identified two narcotics: cocaine (retention time min) and codeine (retention time min.). Both substances were identified on retention parameters and massspectra comparing with reference substances. Also in analyzed extract was detected ecgonine the main metabolite of cocaine (retention time min). This compound was identified on mass-spectra libraries only, because there was not reference standard for chromatography. Detection of this metabolite was possible to establish an approximate time of death of the victim. Conclusion. A sensitive and selective gas chromatography-mass spectrometry (GC-MS) method was developed for simultaneous determination of cocaine and codeine in internal organs of human corps. The GC-MS conditions were developed. The analysis was carried out on a HP-1 column (30 m 0.25 mm, 0.25 μm) with temperature programming, and Helium was used as the carrier gas with a flow rate of 1.0 ml/min. This developed method was successfully used for the detection of cocaine and codeine in human body for forensic identification study. 139

140 CREATE A NEW COSMETIC PRODUCTS WITH THE USE OF MEDICINAL PLANTS BIOMASS Fedorova O., Zayarnuk N., Petrina R., Konechna R., Krvavych A., Novikov V. National University "Lviv Polytechnic", Lviv The main direction of cosmetology in in the 21 st century is to usage cosmetic products wich may prevent biological aging and their combination with the with vitamins, medicinal plants, phytohormones, algae extracts, minerals etc. Since the skin reflects the physiological state of the body, there is also need for oral cosmetic products. As a perspective in anti-age therapy we see the combined treatment, for example: simultaneous usage of external skin cream and some internal supplements with antioxidants [1]. The subject of our research is the development of new therapeutic and cosmetic products for anti-aging skin care based on extracts of biomass of medicinal plants - Arnica montana, Gladiolus imbricatus, Echinacea purpurea, Calendula officinalis. They are obtained by in vitro culture techniques, which offers great opportunities conservation of medicinal plants. Arnica montana is a unique medicinal plant of the family Asteracea, which contains biologically active compaunds: essential oils, plant pigments, phytosterol, resinous substance, waxes, gums, alkaloids, tannins, choline, betaine, flavonoids, polyphenols, sulfur compounds, inulin, arnitsyn, organic acid. Preparations of Arnica montana are widely used as a tonic, stimulating, hemostatic, choleretic, anti-anxiety, anti-inflammatory agents. Plant extract is effective in treatment of rosacea, acne, dandruff, hair loss, and used in skincare products for of oily and acne prone skin. Gladiolus imbricatus rare wild species, belonging to the Iridaceae family and Red listed in Ukraine. It shows medicinal properties thanks to glycosides, flavanoids, polysaccharides, vitamins and essential oils. In folk medicine this plant is used as an analgesic, vitamin, antiallergic, lactogenic agent. Additionally its crushed corn demonstrates healing properties and thus applied wounds and ulcers. Echinаcea purpиrea is a unique medicinal plant of the family Asteracea, contains several groups of biologically active compounds, such as flavonoids, coffee acids, polysaccharides, essential lipids, vitamins, alkylamides. In addition, it contains the following minerals: calcium, potassium, cobalt, selenium, lithium and so on. Plant extract is effective in healing wounds, burns, ulcers, under reduced vitality and demonstrates anti-inflammatory, antimicrobial and antiseptic effects. Calеndula officinаlis is a unique medicinal plant of the family Asteracea, contains carotenoids, flavonoids, essential oil, saponins, bitter substances kalenden, resin and tannin, mucilage, inulin, organic acids, phytosterols, enzymes, vitamin C, alkaloids and triterpene oligoglycosides. Plant extract is effective for treatment of cracked skin, herps, and in acne infections cracks in the corners of the mouth. Its extract is widely used during such diseases as pityriasis versicolor, seborrheic dermatitis, eczema, purulent skin rash and freezing. As the raw material for applying are used rhizomes, roots, dried flower baskets of natural habitat. This leads to the destruction of plants wild populations. Thus cultivation and receiving raw materials to industrial plantations are quite expensive [2,3]. Our research is based on classical techniques of isolated cells culture, tissues and organs of plants. We have used Murashige & Skoog medium containing Indole-3-acetic acid, α-naphthaleneacetic acid, kinetin, which results in high viability and rapid germination of seeds on days at о С. We have conducted a quantitative and qualitative analysis of callus mass, and found the following composition of biologically active compounds: flavonoids, tannins, essential oils, carotenoids and chlorophylls. In the studied objects were detected ferulic and other organic acid, quercetin, rutin, hesperidin. The quantitative content of flavonoids in terms of rutin in Arnica montana % [4]. We have used obtained plants extracts with a high content of secondary metabolites, particularly tannins, essential oil, flavonoids and ascorbic acid to create nutrient emulsion for problematic atonic skincare (age 40+) which might be used in a comprehensive program in anti-age therapy. 140

141 Comparative analysis of wholesale price lists of pharmaceutical companies and retail pharmacy network of medicinal products which include in it s composition Arnica montana allowed to establish that cost of the proposed nutrient emulsion is UAH, Is much cheaper, despite the fact that apart from Arnica montana offered samples of writing a prescription contains other ingredients that exhibit specific pharmacological effect. Our results demonstrate prospects for the usage of medicinal plants callus mass as a raw in the cosmetic products. REFERENCES 1. Bashura A.G., Polovko N.P., Kovaleva T.N., Gubchenko T.D. Basics practical cosmetology P.1. Kharkiv: NFaU, Zolotye stranicy; 2004; Lutova L.A. Biotechnology of higher plants. St.-Peterburg University: Solodovnіchenko N.M., Zhuravlev M.S., Kovalev V.M. Medicinal plant material and fitodrags. Kharkov: MTKbook; Pertina R.O, Masnuk Y.T. Calussgenesis in culture in vitro Arnica montana, J. of National Univ. "Lviv Polytechnic" 2008; 609: bavsvta janmrtelobis problemebi da gadawris gzebi saqartvelosi xazaraze q., jafarize n. saqartvelos Sromis, janmrtelobisa da socialuri dacvis saministro, Tbilisi, saqartvelo gansakutrebul aqtualobas izens bavsvta janmrtelobis problemebi saqartvelosi, vinaidan socialurma da ekonomikurma Zvrebma seriozuli zemoqmedeba moaxdina qveynis mosaxleobaze bolo atwleulebsi, rac aisaxa reproduqciuli asakis mosaxleobis janmrtelobasi da am mxriv mnisvnelovania arinisnos Sobadobisa da bunebrivi namatis Semcireba, rac Cveni qveynistvis SemaSfoTebelia. epidemiologiuri monacemebit mosaxleobis cxovrebis donis daqveitebam gamoiwvia misi janmrtelobis mdgomareobis gauareseba. garemos dabinzurebam (haeri, wyali, niadagi), arabalansirebulma kvebam, genmodificirebulma sakvebma produqtebma, arasrulfasovanma samedicino daxmarebam wlebis ganmavlobasi safuzveli Cauyara ekologiurad gapirobebuli daavadebebis zrdis tendencias. miuxedavad mrewvelobis ganvitarebis tempebis Semcirebisa, arinisneba garemos xarisxis mkvetri gauareseba, rac gamowveulia avtotransportis intensivobis swrafi zrdit, avtotransportis gauamartaobit (ar arsebobs teqnikuri datvaliereba), sawvavis xarisxis kontrolis sistemis arasrulyofilebit. zemocamotvlil problemebs amzafrebs isic, rom garemosa Tu yofacxovrebasi mravladaa uaryofitad moqmedi faqtorebi (siraribe, ganatlebis dabali done), rac damatebit uaryofit gavlenas axdens mosaxleobis janmrtelobaze, kerzod, bavsvta janmrtelobaze. dedata da bavsvta janmrtelobis macveneblebi jandacvis erovnuli sistemebisa da qveynebis socialuri ketildreobis Sefasebis umtavres indikatorebs warmoadgens. saqartvelos kanonis janmrtelobis dacvis Sesaxeb 133-e muxlis Sesabamisad, bavsvta sikvdilianobisa da avadobis Semcirebis samedicino aspeqtebis martva, bavsvebistvis realurad SesaZlo umarlesi donis samedicino daxmarebis, mat Soris, upirveles yovlisa, pirveladi samedicino daxmarebis armocena janmrtelobis dacvis sistemis prioritetuli amocanaa. 141

142 Catarebuli kvlevis dokumentis SemuSavebisas gamoyenebuli metodologia itvaliswinebs dokumentebis moziebasa da analizs, kerzod, saqartvelos kanonmdeblobis ganxilvas, qveyanasi moqmedi saxelmwifo programebis mimoxilvas da analizs, raodenobrivi da Tvisobrivi monacemebis analizis safuzvelze arsebuli situaciis Sefasebas. saqartvelosi ukanaskneli ati wlis ganmavlobasi, qveynis ekonomikuri ganvitarebisa da jandacvis seqtorsi gatarebuli reformebis Sedegad, sayuradrebo progresi SeiniSneba dedata da bavsvta sikvdilianobis Semcirebis TvalsazrisiT. Cvil bavsvta sikvdilianobis done arnisnul periodsi TiTqmis orjer Semcirda, Tumca saqartvelosi Cvil bavsvta sikvdilianoba maralia evropis ganvitarebuli qveynebis macvenebeltan SedarebiT. saqartvelo ert wlamde asakis bavsvta sikvdilianobis macveneblis mixedvit 42-e adgilzea. amastanave, wlamde asaksi gardacvalebis SemTxvevaTa 60% neonatalur periodze, xolo 85% adreul neonatalurze modis. rac Seexeba qveyanasi xut wlamde asakis bavsvta sikvdilianobas, 2000 wlidan 2011 wlamde periodsi 24.9-dan 12.4-mde Semcirda. rac Seexeba Sobadobisa da bunebrivi namatis macveneblebs kvlav 1995 wlis monacemebs mivuaxlovdit (cxrili 1). cxrili 1. bunebrivi mozraobis zogadi macveneblebi, saqartvelo, cocxalsobile bi gardacvaleba bunebrivi mateba qorwineba ganqorwineba weli raodenoba macvenebeli 1000 mosaxleze raodenoba macvenebeli 1000 mosaxleze raodenoba macvenebeli 1000 mosaxleze raodenoba macvenebeli 1000 mosaxleze raodenoba macvenebeli 1000 mosaxleze dedata, Cvil da mcirewlovan bavsvta janmrtelobis kutxit arsebuli problemebis gadasawrelad da mati janmrtelobis mdgomareobis gasaumjobeseblad didi yuradreba etmoba saxelmwifo programebsi dedata da bavsvta samedicino servisebis integracias. 142

143 qveyanasi moqmedebs dedata da bavsvta janmrtelobis programa, romlis mizania dedata da axalsobilta sikvdilianobis Semcireba orsulta efeqtiani patronajisa da maralkvalificiuri samedicino daxmarebis geografiuli da finansuri xelmisawvdomobis gazrdis gzit. unda arinisnos, rom saqartvelos Sromis, janmrtelobisa da socialuri dacvis saministrosi Seiqmna dedata da bavsvta janmrtelobis sakoordinacio sabwo (saqartvelos Sromis, janmrtelobisa da socialuri dacvis ministris 2013 wlis 16 maisis # /o brzaneba), romlis mizania qveyanasi dedata da bavsvta janmrtelobis xelsemwyobi RonisZiebebis dagegmvis, ganxorcielebisa da monitoringis meqanizmebis ganvitarebis xelsewyoba. sabwo Seiswavlis dedata da bavsvta avadobisa da sikvdilobis monacemebs da qveyanasi arsebuli ante-, peri- da postnataluri samsaxurebis simzlavreebis Sefasebis safuzvelze amzadebs winadadebebs dedata da bavsvta janmrtelobis erovnuli politikisa da saxelmwifo programebis prioritetebis gansazrvris miznit. sakitxis aqtualobidan gamomdinare kompleqsurad moxda bavsvis janmrtelobaze zrunvis sistemis Sefaseba da Camoyalibda sistemis gaumjobesebis ZiriTadi mimartulebebi. problemis gadawris gzebi. Catarebuli kvlevis Sedegad, movaxdinet problemuri sakitxebis identificireba da davsaxet mati gadawris mimartulebebi, rac itvaliswinebs rogorc mosaxleobis pasuxismgeblobis gazrdas da CarTulobas, iseve saxelmwifo politikis gazlierebas bavsvze zrunvis kutxit (janmrtelobisa da socialuri dacvis sistemis farglebsi). Catarebuli kvlevis Sedegad, SegviZlia davaskvnat, rom bavsvis janmrtelobaze zrunvis sistemis gaumjobesebis miznit mnisvnelovania zrunvis momsaxurebis ganvitareba da gazliereba, janmrtelobis dacvis sistemis gamartva da Tanamedrove teqnologiebis ganvitarebis xelsewyoba, ojaxebis gazliereba siraribis dazlevis kutxit, socialuri samsaxuris gaaqtiureba. aucilebelia socialuri utanasworobis likvidaciis kursis SenarCuneba, arsebuli sizneleebis gadalaxva, mosaxleobis pasuxismgeblobis gazrda sakutari janmrtelobis mimart, saxelmwifo finansebis mobilizeba da mizanmimartuli xarjva miznobrivi programebis ganxorcielebis gzit. literatura 1. gamyrelize amiran, atuni rifat, gocaze giorgi, maklehosi lora, janmrtelobis dacvis sistemebi gardamavali periodisi saqartvelo, jandacvis sistemis evropis observatoria, evropis regionuli ofisi. Kopenhageni: dania. 2. efeqtiani martvis gamowvevebi saqartvelosi, 4 magaliti. Tb.: saqartvelos kanoni janmrtelobis dacvis Sesaxeb, 4. statistikuri cnobari, janmrtelobis dacva, saqartvelo, 2012, Tbilisi, saqartvelos Sromis, janmrtelobisa da socialuri dacvis saministro, daavadebata kontrolisa da sazogadoebrivi janmrtelobis erovnuli centri, 5. urusaze ramaz, sazogadoebrivi jandacva, q. Tbilisi; 6. Cxetia Teimuraz. samedicino daxmarebis xarisxis Sefaseba (metoduri rekomendaciebi), saqartvelos Sromis, janmrtelobisa da socialuri dacvis saministros samedicino daxmarebis, farmacevtuli saqmianobisa da narkotikebis legalur brunvaze kontrolis inspeqcia. Tbilisi, gamomcemloba farmacevtuli macnemedea;

144 kamelinis substanciasi biologiurad aqtiuri nivtierebebis Seswavla gazuri qromatografiuli - mas speqtometruli (GC-MS) metodit 1 murtazasvili T., 1 maxaraze r., 2 joxaze m., 1 imnaze n., 1 nozaze b. 1 Tbilisis saxelmwifo samedicino universiteti, farmacevtuli da toqsikologiuri qimiis departamenti; 2 farmakognoziis departamenti; axvledianis 22, 0108 Tbilisi, saqartvelo eqim benediqte marlakelizis mier, me-20 saukunis 50-ian wlebsi eqsperimentuli da klinikuri kvlevebis safuzvelze, SemuSavebuli iqna preparati kamelini. preprats avtori Rebulobda naturaluri Taflidan gamoyofili naxsirwylebis fraqciis bazaze. is preparats swavlobda Cirqovani Wrilobebis Sexorcebaze, antibaqteriul moqmedebasa da simsivnur daavadebebze [1]. avtoris gardacvalebis gamo arnisnul preparatze kvlevebi SeCerebuli iyo garkveuli droit wlidan qartul farmacevtul bazarze daregistrirebulia kamelinis xuti wamlis forma (saineqcio xsnari-kamelini M1, myari Jelatinis kafsulebi - kamelini M2, malamo kamelini M3, supozitoria kamelini M4 da yelis sprei - kamelini flu). arnisnuli formebi gamoiyenebian sxvadasxva daavadebebis dros rogorc imunuri sistemis mastimulirebeli da antimikrobuli sasualebebi [2]. kamelinis preparatebis mosamzadeblad substanciis saxit gamoiyeneba kamelinis liofilizati, romelic naturaluri Taflis gadamusavebit mirebuli Sualeduri produqtis - kamelini 100%-is (avtori preparatebis mosamzadeblad iyenebda arnisnul fraqcias) liofilizats warmoadgens. arnisnuli produqti Seicavs biologiurad aqtiur nivtierebebs: fenolebs, furanebs, organul mjaveebs da sxva. substanciis da preparatebis standartizaciis miznit normatiul dokumentebsi Setanilia fenoluri da furanuli SenaerTebis jamuri gansazrvris metodebi [3]. Cvens mier gamoqveynebul publikaciebsi moyvanilia masalebi kamelinis substanciebsi da preparatebsi arnisnuli naertebis jamuri gansazrvris sxvadasxva metodebze. kvlevis mizans Seadgenda mravalkomponentiani kamelinis substanciasi Semavali konkretuli ingredientebis identifikacia Tanamedrove gazur qromatografiuli mas speqtrometruli analizis metodit (GC-MS), rac SemdgomSi SesaZlebels gaxdis moxdes mati raodenobrivi Semcvelobis gansazrvra maralefeqturi sitxuri- an gazuri qromatografiis gamoyenebit. eqsperimentul kvlevebs vatarebdit Clarus 500 PerkinElmer markis gazur qromato-mas speqtrometrze. sveti DB5, svetis sigrze 30 m, diametri mkm, ionizaciis xarisxi 70 ev. Eeqsperimentis dros icvleboda nimusis momzadebis wesebi da qromatografirebis pirobebi. obieqtebidan aqroladi naertebis izolirebisatvis eqstrahentad SevarCieT qloroformi - metanolis narevi (8 : 2) (v/v), 4-jerad ultrabgerit gamowvlilvas vawarmoebdit wutis ganmavlobasi, qloroformian gamonawvlils vfiltravdit uwylo natriumis sulfatsi, vaortqlebdit, fialaze darcenil msral nasts vxsnidit metanolsi da mirebul eqstraqts vatarebdit aparatsi Semdeg pirobebsi: mozravi faza -heliumi, misi miwodebis sicqare 1 ml/wt, injeqtoris temperaatura 250 C transferlainis temperatura 295 C, Rumlis temperatura 40 C, dayovneba 3 wt, temperaturuli gradienti 15 C 150 C dayovneba, 20 C/wT 250 C dayovneba 1 wt, 35 C/wT 310 C dayovneba 2 wt. injeqtirebis moculoba 1 mkl, ionebis registraciis rejimi - TIC. ionebis dereqtireba warmoebda amu diapazonsi. 144

145 obieqtebidan araaqroladi naertebis izolirebisatvis obieqts vxsnidit metanolsi, amovaqrolebdit azotis nakadis qves, darcenil masa 20 mg gadagvqonda flakonsi, vamatebdit BSTFA - etilacetati (3:2) (v/v) 50 mkl narevs. Semdeg flakons exureba Tavi, Tavsdeba TermostatSi 70 C temperaturaze 30 wutis ganmavlobasi da mirebuli saanalizo sinjis moculoba qromatografirebistvis Seadgenda 1 mkl. speqtraluri analizis (GC-MS) Sedegad kamelini 100%-is da kamelinis liofilizati - s SemadgenlobaSi ganisazrvra Semdegi naertebi: rzemjava (4.43 wt), levulis mjavas nawarmi (5.26 wt), α-rzemjava (5.30 wt), gliceroni (6.29 wt), 3-meTil 2-furankarboqsimJava (6.80 wt), 2-furankarboqsimJavas nawarmi (7.23 wt), 5-meTil-2-furankarboqsimJava (7.76 wt), furanis nawarmi (7.87 wt), furankarboqsimjavas nawarmi (8.15 wt), 2-furanacetaldehidis nawarmi (8.87 wt), anhidril-beta-glukoza (9.04 wt), qsilofuranoza (9.22 wt), arabinoheqsonis mjavas nawarmi (9.44 wt), fruqtoza (9.57 wt), glukofuranoza (9.76 wt), gulonis mjava (10.29 wt), piranis nawarmi (10.69 wt) (sur. 1-3) sur. 1. kamelini 100%-is gazur-qromatografiuli mas-speqtrometruli (GC-MS) qromatograma sur. 2. kamelin liofilizat -is gazur-qromatografiul mas-speqtrometruli (GC-MS) qromatograma 145

146 (mainlib) Furan-2-carboxylic acid, 3-methyl-, trimethylsilyl ester sur. 3. kamelin liofilizat -Si da kamelini 100%-Si identificirebuli 3-meTil-furan- 2 karboqsimjava mirebuli mas speqtrebidan da qromatogramebidan Cans, rom kamelini 100%-is da kamelinis liofilizati -s Tvisobrivi Semadgenlobis monacemebi ZiriTadad aris ertnairi. mciredi gansxvaveba gamoixateba 100%-Si suqsinilacetonis (8.40 wt) da Saqrovani naertebis (12.1 wt) ufro meti Semcvelobis gamo. Cvens mier SerCeul gazur qromatografiul - mas speqtrometrul analizis pirobebsi (xelsawyos monacemebze dayrdnobit) Seswavlilia kamelinis substanciebis (kamelini 100%-is da kamelinis liofilizati -s) qimiuri Semadgenloba, rac sasualebas izleva mowme-standartebtan SedarebiT moxdes TiToeuli komponentis Tvisobrivi da raodenobrivi gansazrvra. literatura 1. Маглакелидзе В.С. Лечебное свойство препарата Камелин. Тб.: Изд.: Сабчота Сакартвело; 1966: Pharmexpert market research center. ФАРМРЫНКИ СТРАН КАВКАЗСКОГО РЕГИОНА. М.: 2011; T. murtazasvili, baxtaze n. da sxv. maralefeqturi sitxuri qromatografiuli metodit furfurolis Tvisobrivi da raodenobrivi gansazrvris metodis validacia preparat kamelin M1 -Si. eqsperimentuli da klinikuri medicina 2013; 4: reziume kamelinis substanciasi biologiurad aqtiuri nivtierebebis Seswavla gazuri qromatografiuli - mas speqtometruli (GC-MS) metodit 1 murtazasvili T., 1 maxaraze r., 2 joxaze m., 1 imnaze n., 1 nozaze b. 1 Tbilisis saxelmwifo samedicino universiteti, farmacevtuli da toqsikologiuri qimiis departamenti; 2 farmakognoziis departamenti; axvledianis 22, 0108 Tbilisi, saqartvelo Catarebulia kvlevebi gazuri qromatomatografia mas speqtrometruli (GC-MS) metodis gamoyenebit kamelini 100%-is (Sualeduri produqti) da kamelinis liofilizati -s (substancia) qimiuri Semadgenlobis gansazrvrisatvis. eqsperimentuli kvlevis safuzvelze SerCeulia analizis CatarebisTvis optimaluri pirobebi: mozravi faza - heliumi, misi miwodebis sicqare 1 ml/wt, injeqtoris temperaatura 250 C transferlainis temperatura 295 C, Rumlis temperatura 40 C, dayovneba 3 wt, temperaturuli gradienti 15 C 150 C dayovneba, 20 C/wT 250 C dayovneba 1 wt, 146

147 35 C/wT 310 C dayovneba 2 wt. injeqtirebis moculoba 1 mkl, ionebis registraciis rejimi - TIC. ionebis dereqtireba warmoebda amu diapazonsi. dadgenilia kamelinis 100% xsnaris da kamelinis liofilizatis qimiuri Semadgenlobebis identuroba. mciredi gansxvaveba gamoixateba 100%-Si suqsinilacetonis (8.40 wt) da Saqrovani naertebis (12.1 wt) ufro meti Semcvelobis gamo. Catarebuli kvlevebi izleva SesaZleblobas TiToeuli ingredientisatvis SemuSavdes raodenobrivi gansazrvris metodebi da SesaZlebeli iyos arnisnuli substanciisgan damzadebuli preparatebis falsificirebaze kontroli. SUMMARY STUDY OF BIOLOGICALLY ACTIVE COMPOUNDS IN SUBSTANCE OF KAMELIN BY GAS CHROMATOGRAPHY MASS SPECTROMETRY (GC-MS) METHOD 1 Murtazashvili T., 2 Jokhadze M., 1 Makharadze R., 1 Imnadze N., 2 Nozadze B. 1 Tbilisi State Medical University, Department of Pharmaceutical and Toxicological Chemistry; 2 Department of Pharmacognosy, Address: Akhvlediani 22, 0108 Tbilisi, Georgia Was done the study of chemical content of Kamelin 100% (internal product) and Kamelin lyophilisate (substance) using the method of Gas Chromatography Mass Spectrometry. Was developed the optimal chromatographic condition to conduct the respective investigation: mobile phase is helium, flow rate is 1 ml/min, the temperature of injector is 250 C, the temperature of transfer line C, the temperature of the oven is 40 C, retention 3 min, gradient of temperature 15 C 150 C retention, 20 C/min 250 C retention 1 min, 35 C/min 310 C, retention 2 min. the volume of injection is 1 µl, the ion registration in TIC regime and the ion detection in amu frames. Was determined the chemical content identity of Kamelin 100% solution and Kamelin lyophilisate. The non significant difference was admitted in Kamelin 100%, because of little more presence of succinilacetone (8.40 min) and sugary compounds (12.1 min). The conducted study gives the opportunity to develop the quantitative method of analysis for each component in studied substances to control and avoid the falsification of such kind composite product. zogierti sakitxi fsiqoaqtiuri nivtierebebis Semcveli medikamentebis legaluri brunvis axal regulaciebtan dakavsirebit 1 n. nikuraze 2 T. nikuraze, 3 q. buaze 1 Tbilisis saxelmwifo samedicino universitetis socialuri da klinikuri farmaciis departamenti; 2 ivane beritasvilis eqsperimentuli biomedicinis centri; 3 ivane javaxisvilis saxelmwifo universitetis iuridiuli fakulteti Tbilisi, saqartvelo ukanaskneli atwleulis ganmavlobasi narkotikuli sasualebebis, fsiqoaqtiuri nivtierebebis, prekursorebis, mati legaluri brunvis, narkologiuri daxmarebisa da narkodanasaulis winaarmdeg brzolis araerti normatiuli aqti iqna mirebuli. 147

148 mtavrobis iniciativa, jandacvis politika, sakitxis optimizacia-liberalizaciis kutxit, asaxvaa im didi da mzardi sazogadoebrivi interesisa da polemikisa, rac ukavsirdeba am metad mtkivneul sakitxs. Cven mier ganxilul iqna axali regulaciebi, im klinikur-farmakologiuri jgufebis mimart, romelta moxmareba mosaxleobis garkveuli nawilis mier xdeba aramiznobrivad. esenia, ZiriTadad: miorelaqsantebi, sazile, xvelebis, epilefsiis sawinaarmdego sasualebebi. cvlilebata paketi saqartvelos kanonsi wamlisa da farmacevtuli saqmianobis Sesaxeb Seesabameba saertasoriso praqtikis CarCoebsa da analogiebs. eyrdnoba qveyanasi wamlis moxmarebis socialur-kulturul da samartlebriv aspeqtebs (monacemebs) wlebis ZiriTadi cvlilebebi itvaliswinebs narkodanasaulis winaarmdeg brzolas da fsiqoaqtiuri nivtierebebis Semcveli samkurnalo sasualebebis nusxisa da legaluri brunvis wesebis damtkicebas. mravaltagan movitant ramodenimes: - aikrzala I da II jgufistvis mikutvnebuli farmacevtuli produqtis arasrulwlovantatvis miyidva. - II jgufidan I jgufsi gadatanilia: baklofeni, gabapentini, deqstrometorfanis Semcveli konbinirebuli preparatebi (garda sirofebisa), zopikloni, zaleploni da tropekamidi. mat mimoqcevaze gavrcelda igive kontrolis meqanizmebi, rac gansazrvrulia fsiqotropul nivtierebebze. - kodeinis, efedrinis, fsevdoefedrinisa da norefedrinis Semcvel farmacevtul produqtze ganxorcielda sisxlis samartlis pasuxismgebloba. - ganxorcielda II da III jgufis medikamentebis reklasifikacia. Sveicariis, avstriis, gaertianebuli samefos, kviprosisa da sxva mowinave qveynebis, sakanonmdeblo bazata koncefciebis magalitze inicirebul iqna definicia fsiqoaqtiuri nivtierebebis jgufi, romelsic 350-mde nivtierebaa arnusxuli wlistvis mati raodenoba gacilebit naklebi iyo (75 pozicia). jandacvis, Sinagan saqmeta, finansta saministros, aseve parlamentis iuriduli komitetis ZalisxmeviT, momzadda proeqti am jgufis medikamentebis ukanono arxebsi gadinebis, qveynis sazrvarze Semotanis, teritoriaze gamovlenisa da arkvetis RonisZiebaTa Sesaxeb. vinaidan arnisnuli nivtierebebi ar eqvemdebarebian saertasoriso kontrols, mati gamovlena, identifikacia, mraval teqnikur da procedurul winaarmdegobebtan aris dakavsirebuli. amdenad TviTmkurnalobisas wamlis gverditi efeqtebit gamowveuli seriozuli riskebi, ureceptod gacemis pirobebsi mati aramiznobrivi gamoyeneba (ZiriTadad narkotikuli Trobis misarwevad), Savi bazari, saaftiaqo narkomania, iatakqvesa aftiaqebi, regulirebis mirma darca. mati,,teqnologiebis,, Sedegebi ki arafrit Camouvardeba narkotikebis mavne zemoqmedebas. saertasoriso globalurig koncefciis gatvaliswinebit, sakanonmdeblo iniciativasi axali fsiqoaqtiuri nivtierebebis sistematizacia dayvanilia saerto birtvebis definiciaze. Sesabamisad axali mzardi rigis fsiqoaqtiuri nivtierebebi sxvadasxva klinikur - farmakologiuri jgufidan daiyo 9 klasad - rac sagrznoblad aadvilebs identifikaciis laboratoriul metodebs, konkretuli samartaldarrvevebis gamovlenisa da arkvetis faqtebs. 148

149 dreisatvis SeiZleba itqvas, rom Cveni monitoringis jgufi (pirvel da meore etapze) isev afiqsirebs fsiqotropul aftiaqebsi msgavs qmedebebs, naklebad zemoarnisnuli nivtierebebidan, metad sxva fsiqoaqtiuri nivtierebebidan, rogoricaa: ataraqsi, zolofti, grandaqsini, SeiZleba moitxovon mattan ertad antihipertenziulebic an sxva. kvlevis dros gansakutrebit gamoikveta arnisnuli medikamentebis reklasifikaciis pirveli punqtis damsaxureba rac ukavsirdeba im garemoebas, rom sagrznoblad iklo saskolo asakis bavsvta aqtiurma motxovnebma am mediamentebze. daskvnis saxit SegviZlia vtqvat, rom sakanonmdeblo iniciativebi cvlilebata proeqtebi da axali regulaciebi am mimartulebit, arsebuli mwvave problemis gadawris umnisvnelovanesi berketebia, romelebic srul SesabamisobaSia msoflio gamowvevebtan, rogoricaa saaftiaqo da iatakqvesa narkomania, toqsikomania da sxva. literatura 1. v. eriasvili n. nikuraze, socialuri farmacia, Tavi VI. farmacevtuli inforacia. Tbilisi. 2. saqartvelos kanoni wamlisa da farmacevtuli saqmianobis Sesaxeb. 3. saqartvelos kanoni narkotikuli sasualebebis, fsiqotropuli nivtierebebis, prekursorebisa da narkologiuri daxmarebis Sesaxeb. 4. saqartvelos Sromis, janmrtelobisa da socialuri dacvis saministros brzaneba: #331/n 2009w #01-34/n 2011w #01-30/n 2011w #01-32/m 2014w saqartvelos kanonis proeqti wamlisa da farmacevtuli saqmianobis Sesaxeb, saqartvelos kanonsi cvlilebis Setanis Taobaze (#07-3/295, w.) 9. receptis institutis etapobrivi danergva preslerizi. informacia ixilet bmulze: CLINICAL PHARMACY: CURRENT STATUS OF EDUCATION AND PRACTICE IN UKRAINE 1 Krychkovska A., 1 Stasevych M., 2 Lopatynska О., 1 Kurka M., 1 Kushnir N., 3 Bondarchuk О., 1 Novikov V. 1 Lviv Polytechnic National University, Lviv, Ukraine; 2 Danylo Halytsky Lviv National Medical University, Lviv, Ukraine; 3 Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine Current statistics of Clinical Pharmacy and Clinical Pharmacology shows that the U.S. clinical pharmacists working in all hospitals, in the UK clinical pharmacists and only 55 clinical pharmacologists. In the Russian Federation clinical pharmacists, norm 1 per 150 beds or 1 per 500 visits to the clinic. Hospital to be accredited should be doctor and clinical pharmacologist in the state in a number of countries. In studies that have been conducted in the U.S., France, Britain, Germany, Japan and Canada, proved the role of the clinical pharmacist in reducing of the total cost of therapy, the number of complications and drug diseases and related hospitalizations and disability [1, 2]. Therefore, the current is study the dynamics of Clinical Pharmacists in Ukraine conducted by the authors, as well as evaluating the possibilities and prospects of future employment in the labor market. The aim of our study - to analyze the state of higher education for training for the specialty "Clinical Pharmacy" problems and their subsequent employment in health care institutions of Ukraine. The object of study - system of training and employment of specialists for the specialty "Clinical Pharmacy". The subject - the 149

150 theoretical and practical aspects of clinical pharmacy. The study used the methods of systems analysis, monitoring, modeling, and formalization. Results and discussion. Training of specialists in Ukraine for the specialty "Clinical Pharmacy" launched in 1998 by the National Pharmaceutical University (Kharkiv). Since 2001, it began as the Lviv, Ternopil, Bucovina, Crimea and Vinnitsa Medical Universities, as well as the Dnepropetrovsk Medical Academy [3]. In this case, on the State Classification of professions of Ukraine in 2001 on "Professionals in the field of pharmacy" specialty "Clinical pharmacist" provides Code [4]. According to the order of Ministry of Health of Ukraine 385 dated , the specified position is included in the range of pharmaceutical specialties. However, analysis of the experience of health care institutions (hospitals) suggests that experts are not provided with proper jobs. In health care facilities are not prepared to provide separate rooms for clinical pharmacists to provide them with the necessary literature to equip workplaces computer hardware and software connecting to the Internet. Thus the most important thing is that the administration is not ready for the health care institutions of the new workflow system. Studies of providing of the pharmaceutical industry in Ukraine by personnel and analysis of their condition is number of leading national scholars [5-9]. Assessment of the current state and prospects of clinical pharmacy in Ukraine carry our by Prof. Zimenkovsky A. [10]. An earlier analysis of the dynamics of pharmaceutical training staff in higher education institutions of Ministry of Health of Ukraine showed that in years the practical health care was extended with approximately pharmacists and clinical pharmacists around [11]. Thus, the labor market of the pharmaceutical industry annually replenished with new professionals - clinical pharmacists, who are motivated to use knowledge and practical skills for optimal therapeutic effect with minimal financial cost when using the drug. The clinical pharmacist is responsible for reducing morbidity and mortality through pharmaceutical care. However, pharmacoeconomic evaluation of drugs policy provides economic availability of therapy, both for the patient and for society, based on knowledge of drug provision and economic activities of pharmacy school. Therefore, the knowledge and skills necessary future clinical pharmacist directly related to changes in its role and responsibilities in the health care system and the drug of the population. Professor M. Slabyi developed method which studied needs in clinical pharmacist. The methodology served as the provisions of the order of Ministry of Health of Ukraine 33 dated "About the staffing ratios and typical staffing of health facilities of Ukraine", according to which a clinical pharmacist position is provided for each clinic, located in cities with populations over 25 thousand people and which have 25 or more positions of doctors. According to the Ministry of Health of Ukraine established norm was determined the need for clinical pharmacist for polyclinics, which is 1069 clinical pharmacists [12]. In Ukraine, operates clinics in 2310 and 2900 hospitals [12]. The results of our preliminary calculations showed that for the functioning of all health facilities should be approximately 4000 clinical pharmacists. This is assuming that each hospital will provide clinical pharmacist position and the number of clinics that are willing to hire a clinical pharmacist is less than 45%. Thus, the number of trained before 2010 clinical pharmacists, specialists such as 1200 was only a third of the health care needs of Ukraine. We study the readiness of health care and drug provision of the population of Ukraine to the changing role of the pharmacist. Thus, clinical pharmacists to engage in the position of medical representatives, product managers, marketers, etc. have planned many managers of pharmaceutical companies. However, these positions can not be realized all the wealth of knowledge and skills of clinical pharmacists, and for several years he has not only failed to gain the appropriate qualifications, or just pretrain. Employment of clinical pharmacists for the post of pharmacist of the "first table" drug also has failed because the employer is interested in profit and not costly in time dimension, consultations visitors. Even if the owner wants to make a separate pharmacy consultation room, a legitimate influence on the decisions taken by the doctor, as well as feedback from the physician and clinical pharmacist authority will not have. In addition to this, as shown practices, employment of clinical pharmacists for the post of pharmacist of the "first table" pharmacy was only possible after passing a course of post-graduate education and re-training of clinical pharmacists in pharmacy general practitioners. Traditionally, Ukraine has never practiced the right of the last signature of the pharmacist, for example, as in France, and fellow physicians for some time will be taken clinical pharmacist as a pharmacist-informer. To run efficiently, these professionals need to break old stereotypes: clinical pharmacist - not the one who meets the needs of drug provision, and the one who can predict the future consequences of treatment. 150

151 However, appropriate work has not been carried out. Training for the specialty "Clinical Pharmacy" in 2013 year there is already at eight universities in Ukraine. Training for the specialty "Clinical Pharmacy" in Ukraine in 2012 academic year are shown in Table 1. Table 1. The number of students for the specialty "Clinical Pharmacy" in 2012 academic year in Ukraine Institution of higher education City Number of students National University of Pharmacy Kharkiv 18 (1 correspondence) Vinnitsa National Medical University Vinnytsya 24 Dnipropetrovsk State Medical Academy Dnipropetrovsk 7 (44 correspondence) Crimea State Medical University Simferopol 10 Lviv National Medical University Lviv 0 Ternopil State Medical University Ternopil 0 Bukovyna State Medical University Chernivtsi 0 National Medical Academy of Postgraduate Kyiv 0 Education Total However, our research shows that 2005 year, due to the above circumstances, was crucial in training of this specialty. This is clearly evidenced by the number of specialists of "Clinical Pharmacy", which have been prepared in Lviv National Medical University (Table 2). Table 2. Number of LNMU graduates of specialty "Clinical Pharmacy" Year Number of graduates people (6.5%) work as a clinical pharmacist among the 217 graduates of the Lviv National Medical University. 4 people (1.8%) work as clinical pharmacists in health care facilities. Clinical pharmacists work at 4 th City Hospital of Lviv, Lviv National Medical University, pharmacies network D.S, pharmacies of city Lviv, the State Service of quality control of drugs and other health care facilities. Other graduates had retrain Clinical pharmacy on speciality "General pharmacy" for employment. This trend in the dynamics of clinical pharmacists train for the specialty "Clinical Pharmacy" in universities, unfortunately, shows that in Ukraine to experience significant clinical implications of the work of pharmacists will not be achieved soon. In addition to being a skilled specialist will be in 8-10 years, Job do not have created for him at the health care institutions, not addressed the rights and obligations. However, the level of competence acquired knowledge and skills of clinical pharmacists are the most suitable for the positions of pharmacist-inspector and pharmacist-expert in the structure of obligatory health insurance (OHI) [13]. We have developed a draft job descriptions of clinical pharmacist-inspector and pharmacist-expert in OHI system. We have defined also their tasks and obligations. Clinical pharmacist-expert in OHI system: - oversees the selection of drugs and determination of their individual dose for patients based on age, sex, underlying disease and comorbidities; - controls the mode and provides prediction of possible complications with the simultaneous use of several drugs; - carries out information on the most effective and least toxic combination of drugs of specific pharmacological insurance group; - defines analogues of imported drugs and establishes the comparative cost, increasing efficiency and affordability of pharmacotherapy; - monitors compliance with the treatment or medical services provided by medical and economic standards of pharmacotherapy level health facilities, district, region, analyzes of the reasons for the deviation from the standard, if any, and makes the appropriate decision on the need or not to the admissibility of such a correction in the future; - provides information to doctors about new drugs insurance compared with known domestic and foreign agents; 151

152 - provides appropriate pharmaceutical care of doctors and patients in the appointment of insurance prescription drugs; - oversees the side effects of medications; - conducts necessary documentation related to expert assessment appointments medicines to patients; - adheres to the principles of pharmaceutical ethics; - plans work and conducts an analysis of its results, continuously improving their skills. Clinical pharmacist-inspector in OHI system: - provides patients with high quality medical care through redistribution fund and advise doctors and patients about the most effective drugs; - appoints additional financing in the form of charges on individual patient records; - comprises means for individual card from the insurance fund doctors.in negligence, assumption of blunders and shortcomings in the treatment; - selects clinical information about new medications in comparison with well-known domestic and foreign agents; - provides the necessary range and form of insurance formularies of drugs by establishing effective contacts with pharmacies for timely acquisition of necessary volume of medicines according formulary list; - provides accumulation, systematization and dissemination of statistical financial, pharmaceutical and pharmacological information; - participates in clinical trials and bioequivalence of drugs; - conducts necessary documentation associated with the collection and redistribution of funds in the accounts of the fund; - adheres to the principles of pharmaceutical ethics, work plans and analyzes its results, continuously improving their skills. Conducted earlier comparative analysis of the number of trained clinical pharmacists and real need for them of health care system in Ukraine indicates a possible lack of specialists to work within the structure of OHI. Since, the establishment of OHI in the current economic and political realities of Ukraine got a real chance of realization in the near future, which is why the need for such specialists may well increase. Leading Ukrainian pharmaceutical scientists, including Professor Zimenkovsky A., working on the introduction of new directions of professional activity for clinical pharmacists: social pharmacy, social clinical pharmacy, evidence-based social medicine, evidence-based management in health care, historical aspects of clinical pharmacy, modeling of clinical and pharmaceutical activities. Conclusions. Revealed the presence of negative dynamics of the number of trained specialists in "Clinical Pharmacy" in Ukraine. It was established that the prospect of implementing practice clinical pharmacist in the health care system is involved in pharmacological supervision, health insurance, family medicine, disaster medicine, clinical pharmacy management, military medicine, departments of registration and clinical tests of drugs at pharmaceutical companies, State Service for quality control of drugs and medical devices, clinical pharmacists as experts on the quality of therapy, as employees of the regional formulary committees. It is proved that the prospect of further research is to develop new models of clinical pharmacy, including hospital pharmacy (hospital pharmacies), clinical pharmacy (hospital, clinical departments), clinical pharmacy of pharmacists of "first contact" in pharmacies, offices of clinical pharmacist in pharmacies, outpatient clinical pharmacy, clinical pharmacy as a set of private and insurance services, family clinical pharmacy, research clinical pharmacy, clinical pharmacy and pharmacological surveillance, clinical pharmacy in laboratory studies, clinical pharmacy and clinical research, clinical pharmacy for certain types of expertise. REFERENCES 1. Stathoulopoulou F., Papastamatiou L., Lapidakis L., Pharmacy World & Science 1996; 18(6): Munroe WP., Kunz K., Dalmady-Israel C., Potter L., Schonfeld WH. Clinical Therapeutics 1997; 19(1): Chernykh V.P. Visnyk farmatsiyi 2002; 3: Derzhavnyy klasyfikator profesiy. Kyiv: Sotsinform: 2001: Slabyy M.V., Parnovs kyy B.L., Zalis ka O.M., Farmats. Zhurnal. 2005; 2: Slabyy M.V., Farmats. Zhurnal. 2005; 6: Slabyy M.V., Farmats. Zhurnal. 2006; 4: Slabyy M.V., Farmats. Zhurnal. 2006; 3:

153 9. Slabyy M.V., Parnovs kyy B.L., Zalis ka O.M., Farmats. Zhurnal. 2006; 1: Syatynya V.Ya., Nastyukha Yu.S., Zimenkovs kyy A.B., Klinichna farmatsiya, farmakoterapiya ta medychna standartyzatsiya 2012; 12: Slabyy M.V., Farmats. Zhurnal. 2005; 4: Slabyy M.V., Farmats. Zhurnal. 2005; 6: Krychkovs ka, Aelita Myronivna. Naukovo-metodychni pidkhody do formuvannya farmatsevtychnoyi skladovoyi medychnoho strakhuvannya: dys... kand. farm. Nauk. K.: B.v.; 2008:25. SUMMARY CLINICAL PHARMACY: CURRENT STATUS OF EDUCATION AND PRACTICE IN UKRAINE 1 Krychkovska A., 1 Stasevych M., 2 Lopatynska О., 1 Kurka M., 1 Kushnir N., 3 Bondarchuk О., 1 Novikov V. 1 Lviv Polytechnic National University, Lviv, Ukraine; 2 Danylo Halytsky Lviv National Medical University, Lviv, Ukraine; 3 Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine The state of training for the specialty "Clinical Pharmacy" and the prospects for their practice in health care of Ukraine were analyzed. The draft of the job descriptions of clinical expert-pharmacist and inspector-pharmacist for the system of obligatory health insurance was proposed. Keywords: pharmaceutical education, clinical pharmacy, clinical pharmacist, medical insurance. PROLONGS OF DISULFIRAM: IMPROVEMENT OF DOSAGE FORMS 1 Zayarnyuk N., 2 Sobetov B., 1 Vorobii М., 3 Cherpac О., 4 Solovyov O., 1 Krychrovska А., 1 Fedorova О., 1 Novikov V. 1 Lviv Politechnic National University, Lviv, Ukraine; 2 Ukrainian Association of drug dependens and alcoholism, Lviv, Ukraine; 3 Co Ltd «Technolab» Lviv, Ukraine; 4 Shupyk National Medical Academy of Postgraduate Education, Kyiv, Ukraine The task of the development of new dosage forms (LF) prolonged action based on new and well-known active substance with biodegradable polymers as formative excipients using, is solved by researchers of our Department of Technology of Biologically Active Substances, Pharmacy and Biotechnology, Lviv Polytechnic National University. An important component of successful treatment of chronic diseases is to ensure the continuity of the treatment process, which is solved by using drugs (D) prolonged action. For this purpose, use intramuscular injections and implants to create in the subcutaneous tissue (muscle) depot drug substance from which it is slowly released into the general circulation. Compared with implants injectable drugs are more convenient to use, provide precision dosing of the active substance and less traumatic for patients. Injectable drugs - a system with a liquid dispersion medium, which is made by dissolving as well as suspending or emulsifying active substances and excipients in a suitable solvent or mixture of solvents. One way to improve traditional medicine is the creation of combined long-acting drugs, which are complex due to multiple active ingredients affect the pathogenesis of various diseases. However, there are many promising biologically active substances (BAS), the use of which in solution is complicated due to their physicochemical properties. Insoluble substances or combinations of several substances with different physical and chemical properties should be introduced into the liquid dosage form for drug 153

154 development. This goal can be achieved by the use of synthetic polymers that are capable of biodegradation, as excipients [1,2]. Analysis of the literature. Drug addiction and alcoholism are chronic, able to relapse disease. The main problem in the treatment of alcoholism and drug addiction is to maintain compliance. Disulfiram (DSF) (or teturam) is the most common sensitizing tool to create a chemical barrier that prevents alcohol. For over 50 years he was officially registered in all countries as a specific anti-alcohol drug [3-6]. Promising is the use of long-acting DF of DSF into implants and injections intramuscular with different validity and content of 3200 mg of drug substance (DS) for the annual treatment in rehabilitation programs. [7] In EU countries implemented special programs that are designed to assess the significance of DSF in the treatment of addiction. The data obtained show that DSF can be effective treatment for cocaine addiction, which causes a decrease in doses of cocaine use among cocaine -dependent patients with / or without alcohol dependence [8,9]. Research especially the formation of therapeutic remission in patients with opioid addiction, which have shown promising use injectable prolonged drug "Tetlong-250" as a means for the treatment and rehabilitation of patients dependent on opioids been conducted in the Danylo Halytsky Lviv National Medical University in 2009 [10]. Recently, an increasing interest is the possibility of using DSF to treat patients with cancer [11-12]. The objects of study are such as new, biologically active substances synthesized by researchers of our Department of Technology of Biologically Active Substances, Pharmacy and Biotechnology, Lviv Polytechnic National University, also as known DS. The subject of the present study is to develop of new DS prolong action and research and both new and well-known long-acting drugs based on DSF. Results and discussion. Rational choice DF method and the method of obtaining drugs individually selected based on the physicochemical properties of BAS. Excipients - iodegradable polymers selected individually depending on the chosen method and the method of obtaining drugs in a particular DF. Water-soluble preparations and combined preparations with auxiliary co-solvents have been obtained. Constancy of molecular structures of biologically active components have been confirmed by the methods of spectroscopies (Fig. 1,2). Stability of obtaining preparations has been study by thermoanalyses (Fig. 3). Biological activity and toxicity of the obtaining preparations in vitro and in vivo was determined (Fig. 4). The preliminary estimates of prolongation of their action have carried out [13-15]. 154

155 New combined injectable drug prolonged action "Naltetlonh" containing DSF and naltrexon for use in the treatment of alcoholism and drug addiction was developed based on experimental studies. Conditions of interaction of the polymer-carrier with active substances for saving molecules structures of active components and formation of particles in the nanospheres form with a uniform size distribution were proposed. Uniform distribution size of provides to the prolongation of drug activity. Preclinical studies have shown pharmacological activity and moderate toxicity of the drug. Clinical studies have begun [16,17]. We have conducted research on the development of new drugs based on prolonged DSF. Also, we consider the possibility of obtaining a combined injectable drugs based DSF and naltrexone with anti-alcohol and anti-alcohol action by encapsulation of drug substances using copolymers of lactic and glycolic acids (CPLG) in an organic solvent. The obtained preliminary data show promising this method. Microcapsules containing shell in the middle of CPLG active substance DSF and naltrexone were prepared. Development of optimal composition, choice of excipients and methods of deposition are the prospects for further research. Research the possibility of using both new and already known prolongs DSF in the treatment of alcohol and drug addiction and cancer are conducted. Mono-therapy patient-volunteer with the 4 th stage prostate cancer that has spread in the pelvic bones, testes, lymph nodes by using the drug "Tetlonh-250" is conducted by us in conjunction with the Ukrainian Association of drug dependes and alcoholism from 2010 to present. Disease proceeded with constant severe pain in the lower half of the body. Patient lost 15 kg over a period of illness. There were severe depression, suicidal thoughts, insomnia. Following the recommendations of oncologists, who observed the patient, he was offered the following treatments: emergency chemical or surgical castration, radiation or chemotherapy, hormone therapy. Since the doctors prognosis were after 1-3 months to be expected fatal. The patient refused from conventional treatment that was offered to him by oncologists. The patient refused from conventional treatment that was offered to him by oncologists. However, he consented to experimental treatment, under which he has got intramuscular DSF injection of 1 ml 1-2 times a month. General data of blood and urine, and special characteristics improved significantly as of January Prostate specific antigen (PSA) decreased with 697 ng/ml to 12.6 ng/ml at a norm of PSA 4 ng/ml. Sleep is recovered without the use of medication. Regular sex resumed 1-2 times a week. The patient gained 15 kg in weight. Overall improved quality of life. Conclusions. Thus, the development of new dosage forms based on DSF is one of the urgent tasks of Medicine and Pharmacy. Properties of long-acting drugs based on disulfiram significantly expand their use in therapy. REFERENCES 1. Alekseev KV, Hrytskova IA, Kedyk SA. Polymers for pharmaceutical technology: training manual, LSAFCT. M.: 2011; 511 [In Russian]. 2. Uchegbu I. Polymers in drug delivery. CRC Talor&Francis Group 2006; Wilkins JN. Traditional pharmacotherapy of alcohol dependence. J. Clin. Psychiatry 2006; 67(14):

156 4. Suh J, Pettinati H, Kampman K, and other. The status of disulfiram: a half of a century later. J. Clin. Psychopharmacol. 2006; 26(3): Mutschler J, Diehl A, Volmert С. and other. Recent results in relaps prevention of alcoholism with Disulfiram. Neuropsychiatrie 2008; 22(4): Sobetov BG, Zimenkovsky BS, Filz OO. 26/02/1999. Antialcoholic means for injections. Patent of Ukraine No Compendium drugs. Ed. Kovalenko VN, Viktorova AP. Morion: 2012: Carroll R, Nich S, Ball E. One year follow up of disulfiram and psychotherapy for cocaine alcohol users: sustained effects of treatment. Addiction 1999; 92: Petrakis IL, Carroll RM, Nich SA. Disulfiram treatment for cocaine dependence in methadone maintained opioids addicts. Addiction 2000; 95: Sobetov B, Filc O. and other. Injection prolong of disulfiram "TETLONG-250" place in the treatment and rehabilitation of drug-dependent patients. Ukrainian J. Psychoneurology 2002; 10(2): 196. [In Ukrainian]. 11. Schweizer MT, Lin J, Blackford A. and other. Pharmacodynamic study of disulfiram in men with nonmetastatic recurrent prostate cancer. Prostate Cancer and Prostatic Disease 2013;16: Conticello C, Martinetti D, Adamo L. and other. Disulfiram, an old drug with new potential therapeutic uses for human hematological malignancies. Int. J. Cancer 2012; 9: Zayarnyuk N, Homyak S, Chervetsova V. Preparation of solubilized preparations based dithioloilidens. Pharm. J. of Ternopil St. Med. Un. 2007; 1: 41 [In Ukrainian]. 14. Kuharska M, Zayarnyuk N, Raevskaya K. Solubilization derivatives of aminonaftohinons. J. of Natinal Univ. "Lviv polytechnic" Chem., Techn. Subst. 2007; 590: 147 [In Ukrainian]. 15. Zaichenko A, Mitina N, Komarovska O. Functional Interoligoelectrolyte Complexes with Micelle-Like Core as Carriers for Poor Soluble Drug Delivery, Reactiv Polimer in inhomogeneous System, in Melts, and at interfaces 203. Drezden, Germany: Zagoriy G, Zayarnyuk N, Sobetov B. Development of THE optimal composition and THE technology OF NEW combined injectable drug with prolonged action based on disulfiram and naltrexone. RJPBCS 2013;4(2): Sobetov BG, Novіkov VP, Shiyanenko OY. 05/25/2012. Method of production of anti-alcoholic and antinarcotic agent for injections Naltetlong. Patent of Ukraine No SUMMARY PROLONGS OF DISULFIRAM: IMPROVEMENT OF DOSAGE FORMS 1 Zayarnyuk N., 2 Sobetov B., 1 Vorobii М., 3 Cherpac О., 4 Solovyov O., 1 Krychrovska А., 1 Fedorova О., 1 Novikov V. 1 Lviv Politechnic National University, Lviv, Ukraine; 2 Ukrainian Association of drug dependens and alcoholism, Lviv, Ukraine; 3 Co Ltd «Technolab» Lviv, Ukraine; 4 Shupyk National Medical Academy of Postgraduate Education, Kyiv, Ukraine The possibility of developing new dosage forms with prolonged action based on disulfiram been analyzed. The injectable combined drug prolonged action "Naltetlong" containing disulfiram for use in the preventive treatment of alcohol and drug addiction was developed. The necessity of explore the possibility both new and already famous prolongs of disulfiram for use in the treatment of alcohol and drug addiction, and cancer was proved. Data on the positive impact of their use on health and quality of life of patients with prostate cancer been received. Keywords: alcohol and drug dependence syndrome, injectable prolonged (injectable long-acting drug), naltrexone, disulfiram, polymers-prolongers 156

157 DETERMINATION OF SILDENAFIL IN BIOLOGICAL FLUIDS Osypchuk L. Danylo Halytsky Lviv National Medical University, Department Of Toxicological And Analytical Chemistry; 69 Pekarska Str., Lviv, Ukraine Sildenafil is citrate of 1-[4-ethoxy-3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5- yl)phenylsulfonyl]-4-methylpiperazine} and belongs to inhibitors of phosphodiesterase type 5 (IFDE 5) [2]. Inhibitors of FDE 5 are effective and safe for erectile dysfunction treatment, but their application is contraindicated with organic nitrates, because simultaneous administration of these preparations can cause hypotensive effect until severe and deaths [1,4-9]. Therefore, chemical-toxicological research of this preparation is an actual task. Material and methods. To develop optimal conditions of Sildenafil isolation from human body biological fluids (blood and urine) and express methods their detection and quantitative determination. Optimal conditions for Sildenafil isolation was developed on model mixtures of 5 ml blood and 20 ml urine containing different quantities of preparation (from 50 to 200 µg). Elaborated conditions of isolation were tested on biological fluids of animals (rats), which was administered Sildenafil in dosage 100 µg/g. Animals weighed g. Technique of Sildenafil isolation from blood. To 5 ml of blood containing Sildenafil added 5 ml of distilled water and 10 ml mixture of acetonitrile with 70 % perchlorate acid (1:1). Samples infused 1 hour while stirring. The mixture centrifuged 15 min at 5000 rpm, supernatant poured; sediment again infused 30 min with 5 ml mixture of acetonitrile with 70 % perchlorate acid (1:1) and centrifuged. Supernatants united, transferred to separatory funnel and adjusted to ph 8 by 30 % solution of sodium hydroxide. Sildenafil extracted twice with 1,2-dyhlorethan (10-ml portions). Methods of Sildenafil isolation from urine. To 20 ml of urine added on drops 10 % trichloroacetic acid solution to ph 2 and left for one hour. Impurities extracted once from acidic environment by 20 ml of hexane. Hexane extract rejected; acidic solution adjusted to ph 8 by 30 % sodium hydroxide and Sildenafil extracted twice with 1,2- dyhloretan (10-ml portions). Sildenafil presence in the extracts was confirmed by thin layer chromatography (TLC). Was used "Sorbfil" TLC plates. Chromatography was performed in two confirmatory solvents systems: ethyl acetate-acetone-diethyl amine (15:10:1) (system 1) and chloroform-acetone-diethyl amine (6:5:1) (system 2). Spots of investigated substance visualized on UV light (while observed a blue-violet fluorescence, characteristic for Sildenafil), followed processing with the Dragendorff s reagent. Quantitative determination of Sildenafil in studied samples was performed by extraction-photometric technique on formation of ion associate with Bromocresol green at ph 4,5 [3]. Formed ion associate was separated from aqueous phase by extraction with chloroform (twice 10 and 5 ml portions); dye was re-extracted in 0.1 M solution of sodium hydroxide to 15 ml final volume. Optical density of blue aqueous solutions was measured on spectrofotometer at λ = 620 nm). For UV spectrometric determination 5 ml of dichloroethane extracts evaporated to dry, dry residue dissolved in 5 ml of methanol. Optical density measured on UV-spectrophotometer at wavelength 292 nm ( cuvette 10 mm). Results and discussion. Developed techniques allow to isolate % of Sildenafil from blood and % from urine. Sildenafil R f value in TLC system 1 is 0.47 ± 0,02, and in system 2 0,6 ±0,01. At extraction-spectrophotometric determination linear dependence of colour solutions adsorptivity ranging from 8 to 120 mg in 15 ml final volume. 157

158 At UV spectrophotometric determination (λ max =292 nm) specific adsorptivity of Sildenafil methanol solution is 272. Conclusion: 1. Optimal conditions for Sildenafil isolation from blood and urine worked out. Efficiency of isolation techniquess tested on biological fluids of experimental animals (rats). 2. For TLC express detection of Sildenafil proposed the following solvent systems: ethyl acetate-acetone-diethyl amine (15:10:1) and chloroform-acetone- diethyl amine (6:5:1). 3. For quntitative determination of Sildenafil proposed extraction-photocolorimetric method founded on reaction with Bromocresol green, and UV-spectroscopy method also. REFERENCES 1. Гамидов С.И., Иремашвили В.В. Действие ингибиторов фосфодиэстеразы 5 типа на сердечно сосудистую систему. Болезни сердца и сосудов 2006; 2: Компедиум 2006-лекарственные препараты. Под ред. В.Н. Коваленко, А.П. Викторова. К.: Морион; 2006: Осипчук Л.І., Галькевич І.Й Вивчення умов екстракції силденафілу органічними розчинниками. Фармацевтичний журнал 2008; 1: Hellstrom WJ. Current safety and tolerability goes out in men with the capable straightened disfunction, receptive coolants of arbiter PDE-5. Int J Clin Pract. 2007; 61(9): Jackson G., Montorsi P., Cheitlin M.D. Cardiovascular safety of sildenafil citrate (Viagra): an updated perspective. Urology 2006; 68(3): Reffelmann T., Kloner R.A. Cardiovascular effects of phosphodiesterase 5 inhibitors. Curr Pharm Des. 2006; 12(27): Sandner P., Hütter J., Hinel T. PDE-5 inhibitors beyond erectile dysfunction. Int J Impot Res. 2007; 19(6): Salloum F.N., Takenoshita Y., Ockaili R.A. et al. Sildenafil and vardenafil but not nitroglycerin limit myocardial infarction through opening of mitochondrial K(ATP) channels when administered at reperfusion following ischemia in rabbits. J Mol Cell Cardiol. 2007; 42(2): Corona G., Razzoli E., Forti G. et al. The use of phosphodiesterase 5 inhibitors with concomitant medications. J Endocrinol Invest. 2008; 31(9): CONSTRUCTED WETLANDS AS SUSTAINABLE BIOTECNOLOGY FOR WASTEWATER TREATMENT Shved O., Stasevych M., Novikov V. Lviv Polytechnic National University Stepana Bandery 12, Lviv, Ukraine Constructed wetlands (CWs), also known as treatment wetlands, were developed in 1950s in Germany and since then have spread as treatment facilities all over the world. Today CWs are often used for treatment of domestic sewage, agricultural effluent, industrial effluent, landfill leachate, urban and highway runoff, etc. [1]. CWs are low cost and energy efficient systems for wastewater treatment, which are based on the use of natural microbial transformations and phytoremediation processes in an artificial environment. These treatment facilities are able to remove organic contaminants, suspended solids, nutrients and pathogens from wastewater. Also recently the studies about removal of pharmaceuticals from wastewater are conducted. The technology of wastewater treatment in CWs are constructional simple and able to provide the necessary level of purification with minimal economic and energy costs, which makes the CWs an optimal solution for wastewater treatment of small residential or industrial objects in developing countries. However, the current understanding of the mechanisms underlying the treatment process is only superficial, and also for the designing and optimization of such systems «black box» approach is often used, that does not always guarantee optimal results. Science still has a lack of understanding of specific internal removal 158

159 mechanisms such as specific nitrogen removal processes, microbial predatory activities, etc. [2]. Therefore, it is reasonable to study the mechanisms of microbial processes, which play a key role in removing pollutants in CWs. The objects of these studies are CWs with horizontal subsurface flow, which are the most common phytoremediation facilities used for wastewater treatment. CWs of this type consist of a layer of filter material (sand, gravel), higher aquatic plants planted in soil filter and wastewater which is moving horizontally below the surface of the filter material. HSSF CWs show high efficiencies of organic matter, suspended solids and pathogens removal, but nitrogen removal efficiency is relatively low and have been reported between 20 and 50 % [3]. The purpose of the studies is to determine the role of different mechanisms of nitrogen compounds transformation in the CWs in order to intensify their work, including determining the role of anammox bacteria [4] and their effect on the removal efficiency of nitrogen and other physical and chemical parameters in the pore water of CWs. To achieve this goal experimental set-up consisting of three ideal mixing model reactors, four laboratory-scale CWs and enrichment anammox reactor is run. To analyze the efficiency of treatment in experimental reactors the following parameters are monitored: temperature, ph, redox potential, dissolved oxygen concentration, inorganic nitrogen (ammonium ions, nitrites and nitrates) as well as qualitative and quantitative composition of microbial associations. Also there is a big interest and potential to discover the efficiency of the pharmaceuticals removal from wastewater in constructed wetlands. REFERENCES 1. Wu S., Kuschk P., Wiessner A., Kästner M., Pang C., Dong R. Response of removal rates on various organic carbon and ammonium loads in laboratory-scale constructed wetlands treating artificial wastewater. Water Environment Research 2013; 85(1): Kadlec R.H., Wallace S.D. Treatment Wetlands, Second Edition. CRC Press, Boca Raton FL: 2009; Wiessner A., Kappelmeyer U., Kaestner M., Schultze-Nobre L., Kuschk P. Response of ammonium removal to growth and transpiration of Juncus effusus during the treatment of artificial sewage in laboratory-scale wetlands. Water Res. 2013; 47(13): Jetten M.S., Niftrik L.V., Strous M., Kartal B., Keltjens J.T., Opden Camp H.J., Biochemistry and molecular biology of anammox bacteria. Crit. Rev. Biochem. Mol. Biol. 2009; 44: EXPERIENCE TEACHING PHARMACEUTICAL SCIENCES IN THE TERNOPIL STATE MEDICAL UNIVERSITY Trygubchak O., Ravliv Yu., Groshovuy T. Ternopil State Medical University, Ukraine To create a European Research and Education Area, improved capacity graduates to employment, improving the mobility of citizens in the European labor market, raising the competitiveness of European higher education in Ukraine introduced a system of education based on the Bologna system [1,2]. It allows you to best provide systematic training to carry out regular monitoring of the assimilation of individual units of educational material and of a course being taught. For students this learning process, on the one hand, shows the advantage of having to prepare a smaller amount of material for each assembly semantic module allows a deeper and more detailed study of certain topics and sections of the course. On the other - eliminates the possibility of gaps seminars and workshops, all kinds of independent work to get the highest score at the finish [3]. Following the example of many of the leading universities of 47 countries [4] education system in "Ternopil State Medical University I. Ya. Horbachersky of Ministry of Health of Ukraine" is based on the Bologna principles [5-7]. In "Ternopil State Medical University I. Ya. Horbachersky of Ministry of Health of Ukraine" teaching students of pharmaceutical faculty in specialties "Pharmacy", "Clinical Pharmacy", "Technology of perfumery and cosmetics". 159

160 Training is conducted in Ukrainian, Russian and English. Training conducted by 14 departments. In the pharmaceutical department operates four producing departments: pharmacognosy with medical botany, pharmaceutical chemistry, clinical pharmacy, management and economics of pharmacy with medicine technology. A unique feature of Ternopil State Medical University is that has the school Intranet page where students can read the work program, schedule of lectures and workshops, presentations, lectures, preparation for lectures and workshops, guidance. Each week, students of pharmaceutical faculty have lecture day, which includes 4 lectures. For 2 hours experienced professors and associate professors give lectures with multimedia supports. In preparation for practical classes students use materials preparation for practical classes that includes basic materials isolated yellow backgrounds, figures, tables, formulas, graphs, some research on the subject links to other web pages. After mastering these materials the night before the practical classes the student has the opportunity to carry out test on the Test Moodle system. The test consists of 24 random questions to each of the proposed five options. Only one answer is clearly correct. This is confirmed by the validity of the test. In some cases (30%) tests include drawings, formulas or have constructed in the form of a situational task. After completion of the test the student is automatically assigned rating. Practical training lasts 6 hours and consists of three parts: pratical part, seminar discussions and test control. In the practical part, students perform practical tasks close to the real problems in pharmacy. For example, get acquainted with the variety of storage conditions of medicines and medical devices, make commodity-transport documents, the receiving of goods purchase on admission, conduct tasks on recipes inventory. As a result, students fill out guidance on the topic of employment. Seminars portion is in the form of interviews, dialogue, role play. Teachers simulate situations that often arise in pharmacies and students offer their solutions on the basis of regulatory documents and learned the material. Thus, for practical classes students take the role of the pharmacist or medical representative. If the student passed the test control system in Moodle, this estimately count for test control. The student may also be tested after the seminar discussion. He will be offered a printed version of 24 tests with 5 answers. Evaluation system is calculated for the 12 point scale. For each of the classes assigned rating and removed as general average. During the study focuses on independent work. This is reflected in the individual assignments, writing essays, coursework, practical training. Basic practical skills handed down in matricales. After the development of practical classes, students sit skilled teachers made in matricals. After a positive result teachers make a note of enrollment in the student metrical book. At the end of each academic year, students have to pass the comprehensive delivery of practical skills called objective structured comprehensive exam (OSСЕ). After completion of the module in each subject semester examination is carried out by each student that had fully nor successfully completed their pratical classes. It takes place in an independent Test Center, and evaluation is performed by scanning operations and estimated by putting in the computer. Theoretical knowledge is controlled, double step at the time. In the final year students sit practically-oriented state exam in producing items. Thus, the implementation of the Bologna education system is an important and necessary for the Ukrainian society because of the need to solve the problem of recognition of Ukrainian diplomas abroad, improving the efficiency and quality of education and therefore the competitiveness of Ukrainian universities and their graduates in the European and global labor market. Joining the Bologna process of promoting the principle of the autonomy of each university in Ukraine, the disappearance of strict administrative and financial control by the public authorities for the operation of the university, effective involvement and use of their own resources in the learning process, organization of training and exchange programs for students and teachers. 160

161 REFERENCES 1. Кудін А. Реалізація в Україні принципів і завдань Болонського процесу: забезпечення мобільності громадян з можливістю їх працевлаштування. Вища школа. 2006; 1: Язвінська О. До спільного освітнього простору. Політика і час. 2006; 2: Ніколаєнко С. Реформа вищої освіти України і Болонський процес. Голос України 2007; 8: Bologna Secretariat, Brussels (2010). "Welcome to the website of the European Higher Education Area: The official Bologna Process website ". Benelux Bologna Secretariat. Retrieved 21 June Грошовий Т.А., Підгірний В.В., Тригубчак О.В., Лелека М.В., Демчук М.Б. Особливості вивчення управління та економіки фармації при переході до кредитно-модульної системи навчання. Матеріали Всеукраїнської навчально-наукової конференції, присвяченої 55-річчю Тернопільського державного медичного університету імені І.Я.Горбачевського МОЗ України «Впровадження нових технологій за кредитно-модульної системи організації навчального процесц в ВМ(Ф) НЗ ІІІ-ІV рівнів акредитації. Тернопіль, ТДМУ: «Укрмедкнига»; 2012: Лелека М.В., Грошовий Т.А., Тригубчак О.В. Досвід викладання організаційно-економічних дисциплін (на прикладі патентознавства, фармакоекономіки, організації та економіки фармації) для студентів фармацевтичних факультетів. Кредитно-модульна система організації навчального процесу у вищих медичних (фармацевтичному) навчальних закладах України на новому етапі: матеріали X ювілейної всеукраїнської навчально-наукової конференції з міжнародною участю (18-19 квітня 2013 року, м. Тернопіль): у 2 ч./ Терноп. держ. мед. ун-т ім. І.Я. Горбачевського. Тернопіль: ТДМУ: 2013; Ч. 1: Грошовий Т.А., Тригубчак О.В., Демчук М.Б., Калушка О.Б. Досвід викладання управління та економіки фармації згідно Болонського процесу. Матеріали навчально-методичної конференції «Підготовка спеціалістів фармації у вищих навчальних закладах: здобутки та перспективи майбутнього» (Луганськ, 10 листопада 2011 року). Луганськ: 2011; SUMMARY EXPERIENCE TEACHING PHARMACEUTICAL SCIENCES IN THE TERNOPIL STATE MEDICAL UNIVERSITY Trygubchak O., Ravliv Yu., Groshovuy T. Ternopil State Medical University, Ukraine The basic scientific work schedule in pharmaceutical sciences departments of ternopil state medical university. Our goals, vission, mission, achievements and basic responsibilities provided for each student studying in our university. FLAVONOIDS AND URSOLIC ACID FROM Epilobium parviflorum, GROWING IN AZERBAIJAN Yusifova J., Movsumov I., Garayev E. Azerbaijan Medical University, Baku, Bakikhanov str., 23, AZ 1022 Epilobium parviflorum (Schreb) D.C. perennial herb about 100 cm in height [1]. Some representatives are widely used in folk medicine for various diseases [2]. Raw materials for the study were prepared at the end of June 2013 in the vicinity of Altiagaj in Khizi region of Azerbaijan Republic. 1.1 kg of ground air-dried above-ground portion was extracted with 96% ethanol in the ratio of 1:8 for 24 hours at room temperature. The extract was decanted off and the extraction was repeated in the same conditions. The extract 161

162 were combined, evaporated under vacuum to ml, ml of water was added. Further evaporation was continued until an aqueous residue was treated with chloroform and left overnight. The precipitated crystals were separated and the mother liquor was treated with ethyl acetate until exhaustion of flavonoids. The ethyl acetate extracts were combined and evaporated to dryness. Paper chromatography established that the precipitated crystals from the water and the ethyl acetate extract contains three flavonoid nature substances. Based on this part of the amount of flavonoids was acid hydrolysis, they were united. As aglycone myricetin was identified and were detected as sugars D-glucose, L-arabinose and L-rhamnose. Preparative paper chromatography obtained 1-3 substances. Substance 1: composition С 21 Н 20 О 12, mp C, R f 0,66 (solvents system (I) n- butanol-acetic acid-water, 4:1:5), R f 0,60 (solvents system (II) 20% CH 3 COOH). Substance 2: composition С 12 Н 20 О 12, mp С, [α] D ( with 0,4; CH 3 OH), R f 0,62 и 0,61 respectively. Substance 3: composition С 21 Н 20 О 13, mp С (methanol), [α] D (with 0,5; dimethylformamide), R f 0,50 и 0,52 respectively. Substances 1-3 have dark fluorescence. Their aglycones yellow. On the basis of the physico-chemical properties the products of acid hydrolysis substance 1 was identified as myricetin-3-o-β-l-rhamnoside, substance 2 myricetin-3-o-β-l-arabinoside, substance 3 myricetin-3-o-β-dglucoside. Myricetin has choleretic and anti-inflammatory properties. Bile properties of myricetin twice larger than that of quercetin [3]. Triterpene acid was isolated from the extract of chloroform, which was identified as ursolic acid. It should be noted that in recent years, it has been found that ursolic acid as oleanolic acid has a broad spectrum of activity [4]. REFERENCES 1. Флора Азербайджана. Баку: 1955; Т. VI: Растительные ресурсы СССР. Цветковые растения, их химический состав, использование. Семейства Нуdrangeaceae Haloragaceae. Ленинград: 1987; Георгиевский В.П., Комиссаренко Н.Ф., Дмитрук С.Е. Биологически активные вещества лекарственных растений. Новосибирск: «Наука»; 1990: Lie Liu Oleanolic acid and ursolic acid: Research perspectives. Journal of Ethnopharmacology 2005; 100: SYNERGISTIC EFFECT OF RUTIN AND NARCISSIN IN THE HEPATOPROTECTIVE ACTIVITY OF FLAVONOID MIXURE IN BUPLEURUM FLAVUM 1 Zheleva-Dimitrova D., 2 Kondeva-Burdina M., 1 Denkov N., 1 Gevrennova R. 1 Department of Pharmacognosy, Faculty of Pharmacy, Medical University - Sofia, 2, Dunav street, 1000 Sofia, Bulgaria; 2 Laboratory of Drug Metabolism and Drug Toxicity, Department of Pharmacology, Pharmacotherapy and Toxicology, Medical University of Sofia, Faculty of Pharmacy, Sofia, Bulgaria Bupleuri radix [roots of Bupleurum L. spp. (Apiaceae)] is one of the most frequently used herbs in Chinese herbal medicine [1]. Most of the secondary metabolites isolated from Bupleurum species belong to the classes of phenolics, lignans, terpenoids (triterpenoids and sterols), mono- and sesquiterpenes (essential oils) and 162

163 polyacetylenes [2-5]. Recently, anti- immunomodulatory, hepatoprotective and antioxidant activities of the polysaccharides [6], anti-proliferative activity of different lignans, and antibacterial activity of essential oils [5] in Bupleurum species was reported. Moreover, Bupleurum triterpene saponins demonstrated anti-inflammatory [7, 8], anti-tumor [9, 10], hepatoprotective [11] and antiviral activities [12]. Based on all these studies, we aimed at investigating in vitro hepatoprotective activity of B. flavum quantified flavonoid mixture (BFF), rutin, and narcissin, isolated from the same mixture, on carbon tetrachloride (CCl 4 ) and tert-butylhydroperoxide (t-buooh) toxicity models in isolated rat hepatocytes. In addition, hepatoprotective effect was evaluated on isolated rat microsomes. Flavonoids from the methanol-aqueous extracts were quantified by highperformance liquid chromatography (HPLC). At a concentration 1 mg/ml of BFF (rutin mg/g, narcissin mg/g ), a stronger antioxidant effect in microsomes was evidenced in comparison with rutin, narcissi, and classical hepatoprotector silymarin. The hepatoprotective effect of BFF significantly reduced the elevated levels of lactate dehydrogenase (LDH) and malondialdehyde (MDA), and ameliorated glutathione (GSH), being most active in t-buooh-induced injury model as compared with CCl 4 toxicity (p < 0.001). In conclusion, rutin in this extract was found to produce synergic action with narcissin in the protection against mitochondrial induced oxidative stress. REFERENCES 1. Bauer R., Franz G. Planta Med. 2010;76: Barrero A.F., Haidour A., Munoz-Dorado M., Akssirac M., Sedqui A., Mansour I. Phytochemistry 1998; 48: Pistelli L. in Bupleurum Species: Scientific Evaluation and Clinical Applications. Pan S.-L. Ed. CRC/Taylor & Francis, Boca Raton; USA: 2006; Liu Y, Zhang T.-T., Zhou J.-S., Wang Q. Helv. Chim. Acta 2008; 91: Akin M., Saracoglu H.T., Demirci B., Baser K.H.C., Kucukoduk M. Rec. Nat. Prod. 2012; 6: Zhao W., Li J.-J., Yue S.-Q., Zhang L.-Y., Dou K.-F. Carbohyd. Polym. 2012; 89: Shah B.N., Seth A.K., Maheshwari K.M. Res. J. Med. Plant 2011;5: Wang Q., Kuang H., Su Y., Sun Y., Feng J., Guo R., Chan K. J. Ethnopharmacol. 2013; 146: Sun Y., Cai T.-T., Zhou X.-B., Xu Q. Int. Immunopharmacol. 2009; 9: Wong V.K.W, Zhang M.M., Zhou H., Lam K.Y.C., Chan P.L., Law C.K.M., Yue P.Y.K., Liu L.J. Evid. Based Complementary Altern. Med. 2013; Art N Nakahara Y., Okawa M., Kinjo J., Nohara T. Chem. Pharm. Bull. 2011; 59: Li T., Peng T. Antiviral Res. 2013; 97: 1. biologiur sitxeebsi buprenorfinis gansazrvris qromato-mas-speqtrometruli (GC/MS) metodis SemuSaveba 1 adeisvili-andrulaze l., 2 joxaze m., 1 maxaraze r., 1 boqolisvili r., 1 gonasvili m. 1 Tbilisis saxelmwifo samedicino universiteti, farmacevtuli da toqsikologiuri qimiis departamenti; 2 farmakognoziis da botanikis departamenti, saqartvelo buprenorfini da misi prolongirebuli forma - suboteqsi dremde gamoiyeneba CanacvlebiT TerapiaSi, rogorc narkomaniisa da arkvetis sindromis, agretve, postoperaciuli tkivilebis mosaxsneli efeqturi sasualeba [3,4]. 163

164 preparati jer Zlieria morfinze. gamoiyeneba peroralurad da intravenurad, intramuskularulad, sublingvalurad da transdermalurad. ZiriTadad usveben xsnaris saxit ineqciebisatvis 0,3 mg/ml [1,2,5]. skrining-testebit mirebuli dadebiti Sedegebis dasadastureblad fartod gamoiyeneba qromatografia mas-speqtrometriit. igi qimiuri naertebis analizis uzustesi metodia, amitom misi gamoyeneba sasamartlo-qimiur eqspertizasi friad aqtualuria. kvlevis mizans warmoadgenda biologiur obieqtebsi buprenorfinis da misi metabolitebis analizis qromato-mas-speqtrometruli (GC/MS) metodis SemuSaveba. kvlevis amocanebi qromato-mas-speqtrometruli analizis pirobebis SemuSaveba optimaluri derivatebis (silireba, acetilireba; TMS, BSTFA, MSTFA) SerCeva, gazuri qromatografiuli deteqtirebis optimaluri pirobebis dadgena. kvlevis masala da metodebi. cocxali da gvamuri sisxli da Sardi. metodika qromato-mas-speqtrometruli (GC/MS) metodi. igi warmoadgens ori damoukidebeli mowyobilobis gzebi qromatografisa da mas-speqtrometris tandems. nivtierebata dayofa warmoebs airad mdgomareobasi 30 m sigrzis kapilarul svetsi, xolo deteqtireba ert kvadrupolis mqone mas-speqtrometrsi Perkinelmer, Clarus 600. metodi dafuznebulia masis muxttan (m/z) Tanafardobis gansazrvrastan. TiToeuli nivtiereba ionizaciis Sedegad isleba Semadgenel fragmentebad, rac izleva sxvadasxva masisa da muxtis mqone ionebis speqtrs e.w. mas-speqtrs. mas-speqtri yvela nivtierebisatvis individualuria. buprenorfinisatvis damaxasiatebelia m/z = 450, 482, 506, 492, 524 [6, 7, 8] saanalizo obieqtis mas-speqtrebis monacemta bazebtan Sedareba nivtierebata identifikaciis mzlavri iararia. eqsperimentuli nawili. eqsperimentis Sedegad davadginet buprenorfinis analizis optimaluri pirobebi: injeqtoris temperatura: civi deteqtoris temperatura C, sveti: DB m X 0,53 mm ID. temperaturuli programa: 40 0 C-dan C-mde (dayovneba 1 wt), C-dan C-mde 5 wt (dayovneba 3 wt). biologiur obieqtebsi sakvlevi nivtierebis qromatografiuli Tvisebebis guumjobesebis miznit, aseve aqroladobis da maral temperaturaze mdgradobis miniwebis miznit mivmartet derivatizacias. saderivatizaciot gamoviyenet: acetilireba (ZmarmJava anhidridi) da silireba (MSTFA, BSTFA; MSTFA + 1% TMCS; BSTFA + 1% TMCS). kvlevis Sedegad davadginet, rom biologiur obieqtebsi, beprenorfinis derivatizaciisatvis optimaluri Sedegi miireba silirebis (BSTFA) SemTxvevaSi. amisatvis vialas, sadac motavsebulia amoqrolebuli biologiuri obieqti vamatebdit 40 mkl masilirebel reagents da 10 mkl etilacetats, vxufavdit, vanjrrevdit da vdgamdit 70 0 C winaswar gacxelebul TermostatSi 20 wutit. mirebuli qromatogramebi da mas-speqtrebi mocemulia suratebze (sur. 1-4). metodi gamoirceva seleqciurobit da specifikurobit buprenorfinis TMS nimusebi stabiluria da gamosadegia GC/MS analizistvis. GC/MS metodit SesaZlebelia buprenorfinis imunoqimiuri strip-testebit mirebuli dadebiti Sedegebis gadamowmeba da dadastureba. 164

165 sur. 1. buprenorfinis Semcveli sisxlis gazuri qromatograma sur. 2. sisxlsi deteqtirebuli buprenorfinis mas-speqtri sur. 3. buprenorfinisa da norbuprenorfinis Semcveli Sardis gazuri qromatograma sur. 4. buprenorfinisa da norbuprenorfinis mas-speqtri 165

166 daskvna: SemuSavebulia buprenorfinis gansazrvris qromato-mas-speqtrometruli metodika, romelic xasiatdeba marali mgrznobelobit da specifikurobit. madloba. avtorebi madlobas uxdian levan samxaraulis saxelobis sasamartlo eqspertizis erovnuli biuros qimiur-narkologiur departaments qromato-masspeqtrometrze Catarebuli analizebisatvis. literatura 1. adeisvili-andgulaze l. narkotikebi. Tb.: 2007; adeisvili-andgulaze l. narkotikuli da fsiqotropuli sasualebebis qrimiurtoqsikologiuri analizi. Tb.: 2007; Минко А., Линский И. Наркология. Новейший справочник. М.: Изд-во Эксмо; 2004: Симонов Е., Изотов Б., Фесенко А., Наркотики. Методы анализа на коже, в её придатках и выделениях. М.: Анархерсис; 2001: Справочник Видал. Астра. Фарм. сервис: 2012; Kintz P., Trasqui A., Manging P. Edel Y. Sweat in opioids uzers with a sweat patch. J. Anal. Toxical Kuntz P., Cirimele V., Edel Y., Jamey C., Mangin P. Hair analysis for buprenorphine and its deal Kulated metabolite by RIA and confirtam by LC-ECD. J. Forens. Sci. 1994; 39: Kuhlman J., Maguilo J., Levine B., Cone E.J. Simultaneous assay of buprenorphine and norbuprenorphine by negative chemical ionization tandem mass spectrometry. J. Anal. Toxical. 1996; 20: reziume biologiur sitxeebsi buprenorfinis gansazrvris qromato-mas-speqtrometruli (GC/MS) metodis SemuSaveba 1 adeisvili-andrulaze l., 2 joxaze m., 1 maxaraze r., 1 boqolisvili r., 1 gonasvili m. 1 Tbilisis saxelmwifo samedicino universiteti, farmacevtuli da toqsikologiuri qimiis departamenti; 2 farmakognoziis da botanikis departamenti, saqartvelo qimiur-toqsikologiur analizsi fartod gamoiyeneba qromato-mas-speqtro-metriuli (GC/MC) metodebi, romlebic gamoircevian gansakutrebuli sizustit. eqsperimentalurad dadgenilia buprenorfinis analizis optimaluri pirobebi: injeqtoris temperatura da moculoba, Rumelis da transferlainis temperatura, temperaturuli gradienti, airis gadaadgilebis sicqare. deteqtireba tardeboda TIC rejimsi acetilirebis, metilirebis da silirebis gamoyenebit. buprenorfinis derifatizaciis optimaluri Sedegebi miireboda silirebis (BSTFA) SemTxvevaSi. nasromsi moyvanilia buprenorfinis Semcveli Sardisa da sisxlis plazmis gazuri qromatogramebi da mas-speqtrebi. SUMMARY DEVELOPMENT OF GAS CHROMATOGRAPHY-MASS-SPECTROMETRIC (GC-MS) METHOD OF DETERMINATION OF BUPRENORPHINE IN BIOLOGICAL FLUIDS 1 Adeishvili-Andguladze L., 2 Jokhadze M., 1 Makharadze R., 1 Kirvalidze T. 1 Tbilisi State Medical University, Department of Pharmaceutical and Toxicological Chemistry 2 Department of Pharmacognosy and Botany, Georgia In chemichal-toxicological analysis used the metod of Gas Chromatoraphy-Mass Spectometry. It is considerend as 166

167 one of the most exact method of analysis of chemical substances. Respectively utilization of this method in determination of widely spread narcotic in biological fluids is important task. As a result of experimental work, was determined optimal conditions of analysis: temperature of injector, fuel and transferline, the thermal gradient, volume of injection, gass-wearing speed of mobile phase. Detection of Buprenorphine was carried by TIC regime, under the NIST data Base. For derivatisation was selected acetilation, metilation and sylitation were performed. The optimal silitation of Buprenorphine was performed by BSTF. In the current is presented the chromatograme and mass-spectra of Buprenorphine isolated from blood and urine. biologiur sitxeebsi dezomorfinis armocenis qromato-masspeqtrometriuli (GC/MS) metodis SemuSaveba 1 adeisvili-andrulaze l., 2 joxaze m., 1 maxaraze r., 1 kirvalize T., 1 gonasvili m. 1 Tbilisis saxelmwifo samedicino universiteti, farmacevtuli da toqsikologiuri qimiis departamenti; 2 farmakognoziis da botanikis departamenti, saqartvelo dezomorfini 4,5-α-epoqsi-17-meTilmorfinan-3-oli - ramdenime welia mraval qveyanasi, mat Soris saqartvelosic gavrcelda rogorc narkotiki da heroinis iafi Semcvleli. aralegaluri forma cnobilia `krakadilis~ saxelit. misi farmakologiuri aqtiuroba 10-jer, xolo toqsikuroba 5-jer aremateba morfinis moqmedebas [7,8]. `krakadilis~ momxmareblis sicocxlis xangrzlivoba sasualod 1 welia [1,2]. ziani, romelsac igi ayenebs organizms, 15-jer aremateba heroins, amitom mas `TviTmkvlel~ narkotiks ezaxian. biologiur sitxeebsi narkotikul sasualebebze skrining-testebit mirebuli dadebiti Sedegebis dasadasturebelad fartod gamoyeneba qromatografia mas-speqtrometriit. igi qimiuri naertebis analizis uzustesi metodia, amitom biologiur obieqtebsi narkotikul nivtierebebis kvlevis qromatomasspeqtrometruli metodis SemuSaveba da arsebulis daxvewa sasamartlo qimiur eqspertizasi friad aqtualuria [3-5]. kvlevis mizans warmoadgenda biologiur sitxeebsi dezomorfinis armocenis qromatomas-speqtrometruli (GC/MS) metodis SemuSaveba. kvlevis amocanebs Seadgenda optimaluri derivatebis (acetilireba, metilireba, silireba SerCeva; b) gazuri qromatografiuli deteqtirebis optimaluri pirobebis dadgena. kvlevis masala da metodebi. cocxali da gvamuri pirebis sisxli, plazma da Sardi. metodika - qromato-mas-speqtrometruli (GC/MS) metodi. igi warmoadgens ori damoukidebeli mowyobilobis gazuri qromatografisa da mas-speqtrometris tandebs. nivtierebata dayofa warmoebs airad mdgomareobasi 30 m sigrzis kapilarul svetsi, xolo deteqtireba ert (MS) da/an or (MS/MS) kvadropolis mqone mas-speqtrometrebsi. metodi dafuznebulia masis muxttan (m/z) Tanafardobis gansazrvrastan. TiToeuli nivtiereba ionizaciis Sedegad isleba Semadgenel komponentebad, rac izleva sxvadasxva masis da muxtis mqone ionebis speqtrs e.w. mas-speqtrs. mas-speqtri yvela 167

168 nivtierebisatvis individualuria. saanalizo obieqtis mas-speqtrebis monacemta bazebtan Sedareba nivtierebebis identifikaciis mzlavri iararia. eqsperimentuli nawili. eqsperimentis Sedegad davadginet dezomorfinis analizis optimaluri pirobebi: injeqtoris temperatura C, Rumelis temperatura 65 0 C, transferlainis temperatura C; temperaturuli gradienti C 0.5 wt; 60 0 C C 10 wt, C C 15 wt; injeqtoris moculoba 1 mkl, svetis sigrze 30 m, fenis sisqe 250 mkm. ionizacia warmoebda 70 ev-it. airmatarebeli heliumi, airis dinebis sicqare 1 ml/wt. dezomorfinis deteqtirebas vaxdendit TIC (ionebis sruli monitoringi) rejimsi, NIST monacemeta bazis gamoyenebit. biologiur obieqtebsi sakvlevi nivtierebis qromatografiuli Tvisebebis gaumjobesebis, aseve aqroladobis da maral temperaturaze mdgradobis miniwebis miznit mivmartet derivatizacias. saderivatizaciod SevarCieT acetilireba (ZmarmJava anhidridi), metilireba da silireba (MSTFA; BSTFA; MSTFA + 1% TMCS; BSTFA + 1% TMCS). kvlevis Sedegad davadginet, rom biologiuri sitxeebsi dezomorfinis derivatizaciisatvis optimalur Sedegs vrebulobdit silirebis [BSTFA] SemTxvevaSi. amisatvis vialas, sadac motavsebuli iyo amoqrolebuli biologiuri obieqti vamatebdit 40 mkl masilirebul reagents da 10 mkl etilacetats. vxufavdit, vanjrrevdit da vdgamdit 70 0 C winaswar gacxelebul TermostatSi 20 wuti. mirebuli qromatogramebi da mas-speqtrebi mocemulia sur sur. 1. dezomorfinis Semcveli sisxlis gazuri qromatograma sur. 2. sisxlsi deteqtirebuli dezomorfinis masspeqtri 168

169 sur. 3. dezomorfinis Semcveli plazmis gazuri qromatograma sur. 4. dezomorfinis Semcveli Sardis gazuri qromatograma GC/MS metodit SesaZlebelia dezomorfinis imunoqimiuri strip-testebit mirebuli dadebiti Sedegebis gadamowmeba da dadastureba. daskvna: SemuSavda dezomorfinis gansazrvris qromato-mas-speqtrometruli metodika, romelic xasiatdeba marali mgrznobelobit da specifikurobit. madloba. avtorebi madlobas uxdian levan samxaraulis saxelobis sasamartlo eqspertizis erovnuli biuros qimiur-narkologiur departaments qromatomasspeqtrometrze Catarebuli analizebisatvis. literatura 1. adeisvili-andrulaze l. da sxvebi. biologiur obieqtebidan metamfetaminis izolirebis metodebis SemuSaveba. Tssu samecniero SromaTa krebuli, tomi XLVI; Tb.: 2012; Веселовская Н.В., Коваленко А.Е. Наркотики. М.: «Триада Х.»; 2000: Eddy N.B. Howes H.A. Studies of Morphine, Codeine and their Derivatives X. Desoxymorphine-C, Desoxycodeine-C and their Hydrogenated Derioatives. Journal of Pharmacology and Experimental Therapeutics. 1935; 55(3): Gahr M., Joy RW Mann, C. Hiemke, Favor IM., Connemann BJ, Schoenfeldt-Lecuona C. Crocodilerevivalof an old drug with new problems. Subst Use Misuse. 2012; 47(7):

170 5. Gurn I., Kriger S., Terell A. Identification and quantitation of amphetamine, methamphetamine, MDMA, pseudoephedrine, and ephedrine in blood, plasma and serum using gas chromatography mass spectiometry (GC/MS). Metods Mol. Bid. 2010: 603. reziume biologiur sitxeebsi dezomorfinis armocenis qromato-masspeqtrometriuli (GC/MS) metodis SemuSaveba 1 adeisvili-andrulaze l., 2 joxaze m., 1 maxaraze r., 1 kirvalize T., 1 gonasvili m. 1 Tbilisis saxelmwifo samedicino universiteti, farmacevtuli da toqsikologiuri qimiis departamenti; 2 farmakognoziis da botanikis departamenti, saqartvelo qimiur-toqsikologiuri analizsi fartod gamoiyeneba qromato-mas-speqtrometruli (GC/MC) metodebi, romlebic narkotikuli nivtierebebis analizsi gamoircevian gansakutrebuli sizustit. eqsperimentis SedegebiT dadgenilia analizis optimaluri pirobebi: injeqtoris temperatura, Rumelis da transferlainis temperatura, temperaturuli gradienti, svetis sigrze, fenis sisqe, airmatarebeli, airis gadaadgilebis sicqare. deteqtireba tardeboda TIC-is rejimsi. dezomorfinis derivatizaciis optimaluri Sedegebi miireboda silirebis (BSTFA) SemTxvevaSi. nasromsi moyvanilia dezomorfinis Semcveli Sardis, sisxlis da plazmis gazuri qromatogramebi da mas-speqtrebi. SUMMARY DEVELOPMENT OF GAS CHROMATOGRAPHY-MASS-SPECTROMETRIC (GC-MS) METHOD OF DETERMINATION OF DESOMORPHINE IN BIOLOGICAL FLUIDS 1 Adeishvili-Andguladze L., 2 Jokhadze M., 1 Makharadze R., 1 Kirvalidze T. 1 Tbilisi State Medical University, Department of Pharmaceutical and Toxicological Chemistry 2 Department of Pharmacognosy and Botany, Georgia In chemichal toxicological analysis used the method of Gas Chromatography-Mass Spectrometry. It is considered as one of the most exact method of analysis of chemichal substances. Respectively utilization of this method in determination of widely spread narcotic in biological fluids is important task. As a result of experimental work, was determined optimal conditions of analysis: temperature of injector, fuel and transferline, the thermal gradient, volume of injection, length of the column, thickness of the layer, gass-wearing speed of mobile phase. Detection of Desomorphine was carried by TIC regime, under the NIST data base. For derivatisation was selected acitilation (acetate anhydride), metilation and sylitation were performed. The optimal silitation of Desomorphine was performed by BSTFA. In the current is presented the chromatograme of Desomorphine isolated from blood and urine, the mass-specter of Desomorphine detected in blood, as well the referral mass-specter of Desomorphine under NIST database. 170

171 RESEARCHES ON BIOLOGICALLY ACTIVE NATURAL ANTHRAQUINONES Muzychkina R., Korulkin D. Faculty of Chemistry and Chemical Technology, al-farabi Kazakh National University, 71 Al-Farabi Avenue, Almaty, , Kazakhstan Natural anthraquinones are submitted by the wide structural variety in wild-growing and cultivated high plants, glues, lichens, mushrooms, sea animals and seaweed etc. as restored, oxidized, condensed, glycoside forms. About 60 individual and complex anthracenic preparations are also successfully used in public and official medicine of different countries for a long time. More than 400 plants of 120 families are used by itself or as various medical "collections", balms, pilled forms. The antiinflammatory, antitumour, antiasthmatic, antihelmint, antiitch, amebicidic, bactericidic and bacteriostatic, immunostimulating, radiosensibilizating, antidermatic action of them was established. They are used at ulcer gastric illnesses and duodenum, at burns and frostbites; they are repellents for termites, hormonal and growth-regulating remedies for plants. The synthetic analogues have more expressed orientation of action and wider spectrum of bioactivity. As a rule, toxicity of such compounds is low; they are quickly removed from the organism without causing by-effects. It tells us about the perspectives of screening of the BAS in the anthraquinone derivatives series. The obtained products can be used by itself, since they show versatile bioactivity, or as the intermediate for the further transformations of structure. It is shown, that the bioactive compounds can be produced in mono-stage reactions with a high degree of selectivity, for example, the selective catalytic reducing C=O, C=C, C=C, C=N, C=N and nitrate-groups and electrochemical oxidation CH 3 >C(O)H>COOH, nucleophilic exchange of C=O and OH-groups and electrophilic substitution on aromatic system of molecules. The new for hydroxyanthraquinons ways in reactions, for example, vinylization at reaction with acetylene and its analogues, C-glycosidation on a lateral bonds, acilization aminoacids and derived of phosphorus acid, production mono- and diadducts with Gryniar s reagent, α-, and β - sulphurization at conditions of reaction sulphytization, condensation with formation of a various type of bond between monomers, ureido- and tioureidoderivatives, reception of pyrimidinoanthrons etc. were revealed. It was shown by complex bioresearches, which the series of nitrogen-, sulfur- and phosphorus- derivatives of the mentioned above hydroxyanthraquinons considerably surpasses in activity the known radioprotectors when irradiating with 137 Cs γ-quanta. The sulphur acid salts protect plants from the action of ionizing radiation. The phosphoric derivatives named above hydroxyanthraquinons promote earlier and complete recovering of bloodcreation processes and adrenocortical system in postirradiation period at the conditions of prolonging of 137 Cs ray energy. Chrysophanol and emodin phosphates influence on sprout of seeds, stimulate or oppress growth of separate parts of plants, what can find its application in selection and in struggle with weeds. Nitro-, ureido-, alkyltio-, sulphurderivatives and phenylhydrazons are active against the activators mealy dew of cucumbers, defeats of millet, wheat. They are much more active, in comparison with analogues on action, concerning rice boll weevil, cereal vermin, and dry rot of potatoes. More than 60 compounds of a various type have mycocide and bactericide activity, bacteriostatic and antivirus action. Chrysophanol shows hormonal activity with relation to vetch, salads and other food cultures. With the complex influence by various nitrogencontaining derivatives of emodin, physcion and chrysophanol with an irradiation the 96% deceleration of growth of tumors or complete necrosis them with change by scar tissues was achieved. The researches on revealing the correlation of biological activity with thin chemical structure of products of modification of chrysophanol, emodin, physcion, aloe-emodin and some other anthraquinone analogues are under the operation. 171

172 kargi farmacevtuli praqtikis (GPP) Seqmna da ganvitareba Wanturia z. Tbilisis saxelmwifo samedicino universiteti, socialuri da klinikuri farmaciis departamenti, saqartvelo XX saukunis msoflio farmacevtuli bazari warmoadgens preparatebis warmoebisa da realizaciis mzlavr da mzard konglomerats. saertasoriso analitikuri kompaniis IMS Health Consulting 2012 w. monacemebis mixedvit msoflio farmacevtuli bazris moculobam Seadgina 940 mlrd. dolari. wina wlebtan SedarebiT SeiniSneboda zrda 6%. eqspertebi uaxloes moavalsic prognozireben mzard tendencias 3-4%-iT. savaraudod 2016 w. miarwevs 1,2 trilions. aseti zrdis mizezad saxeldeba: - demografiuli situacia, kerzod mosaxleobis sociumis struqturasi bavsvebisa da moxucebis raodenobis xvedriti wilis zrda; 172

173 - araxelsayreli ekologiuri mdgomareoba, romelic iwvevs ara mxolod janmrtelobis mdgomareobis gauaresebas, aramed axali patogenuri mikrofloris ganvitarebas, rac axali daavadebebis gamomwvevia; - saomari konfliqturi situaciebi; - migraciuli procesebi; - teqnologiuri katarstrofebis Sedegad gamowveuli epidemiebi; - bunebrivi kataklizmebi da sxva; bolo atwleulsi mzardma motxovnam gamoiwvia farmacevtuli bazris struqturis kardinaluri cvlileba, ramac gazarda motxovna farmacevtze da mis momsaxurebaze. jandacvis msoflio organizaciis (janmo) eqspertebma farmacevtis rolze aqtiuri interesi gamoavlines gasuli saukunis 80-ian wlebsi. sayuradreboa, rom arnisnuli interesi gamoiwvia samedicino momsaxurebis sferosi farmacevtis funqciuri danisnulebis daqveitebam. industriulad ganvitarebul qveynebsi gamoikveta tendencia farmacevti moiazreboda mxolod samkurnalo sasualebebis gamyidvelad. vinaidan is funqciebi, romlebic dakavsirebuli iyo samk. sasualebebis warmoebasa da eqimebis informirebulebaze, Tavis Tavze aires farmacevtuli produqciis warmomadgenlebma. cxadia, es tendenciebi ar Seesabameboda arc farmacevtebis da arc sazogadoebis interesebs, radganac farmacevtuli funqciis mnisvnelobis satanadod Seufaseblobas udaod mivyavart mati profesionaluri codnisa da potenciuri SesaZleblobebis arasakmaris gamoyenebamde, aseve dargis specialistebs aizulebs orientirdnen mxolod ekonomikur interesebze (gazardon realizacia, gaiyidos umeteswilad ZviradRirebuli medikamentebi da sxva). gasuli saukunis 80-ian wlebsi Seiqmna yvela aucilebeli piroba am problemis gansaxilvelad saertasoriso doneze, vinaidan: - Semcirda eqstemporalur wamlis formebze, praqtikulad samkurnalo preparatebis damzadeba xorcieldeboda ZiriTadad sawarmoo pirobebsi; - wamlis realizaciis sferom ganicada arsebiti cvlileba. mag.; ass da iaponiasi wamlebs gascemdnen mxolod eqimebi. - gafartovda realizacia sazogadoebriv savawro obieqtebsi (mag. supermarketebsi). ufro popularuli gaxda s/sasualebebis realizacia fostit, ukanasknel wlebsi internetit. - s/sasualebeis sabitumo realizacias ganaxorcielebdnen mxolod biznesmenebi, romeltac ar gaacndat farmacevtuli ganatleba; - gartulda sxvadasxva seqtoris funqcionireba, rogoricaa: s/sasualebebis SemuSaveba da warmoeba, xarisxis kontroli, momarageba, racionaluri gamoyeneba, farmacevtuli bazris saxelmwifoebrivi regulireba da sxva. - warmoisva problema falsificirebul preparatebze, ramac gamoiwvia sistemis garkveuli pereorientacia. - iset sferosi, sadac tradiciulad dominirebdnen specialistebi samedicino, qimiuri da ekonomikuri ganatlebit, Seiqmna motxovna farmacevtuli ganatlebis specialistebzec. amrigad, Seiqmna situacia, ertis mxriv farmacevtuli codna armocnda motxovnadi, meores mxriv arasakmarisi. iniciatorad gamocnda profesiuli gaertianeba saertasoroso farmacevtuli federacia, (FIP Federation International Pharmaceutique), romelic, rogorc arasamtavrobo organizacia didi xnis manzilze TanamSromlobda janmo-stan da aqtiurad mxars uwerda mis programebs samkurnalo sasualebebze w. janmo-s eqspertebis mier SemuSavebul iqna strategia `janmrteloba yvelas 2000 wlisatvis~, romlis safuzvelze sawiro gaxda xelaxla gansazrvruliyo 173

174 jandacvis sferos musakebis funqciuri danisnuleba, rac gamoikveta janmo-s konferenciebze: - evropis regionaluri konferencia `farmacevtis roli sacalo vawrobis da savadmyofos aftiaqebsi~ (madridi, espaneti, 1998w) - pirveli saertasoriso konferencia - `farmaciis arsi da farmacevtis funqciebi~ (niu deli, indoeti, 1988 w.) - meore saertasoriso konferencia - `farmacevtuli momsaxurebis xarisxi sargebeli saxelmwifosa da sazogadoebistvis~ (tokio, iaponia, 1993 w.) - mesame saertasoriso konferencia - `farmacevtebis momzadevba saswavlo programebis SemuSaveba~ (kanada, 1997 w.) - meotxe saertasoriso konferencia - `farmacevtis roli TviTmkurnalobaSi~ (haaga, niderlandebi). am konferenciebis daskvnebis analizi cxadyofs, rom aqcenti gaketda ara mxolod ganatlebuli specialistebis aucileblobaze, aramed pirovnuli Tvisebebis srulyofaze, romlebic profesiul unarebtan ertad specialists sasualebas miscems Rirseuli adgili daikavos sazogadoebrivi jandacvis sistemasi. yrilobis monawileebi xazgasmit arnisnavdnen Sesabamisi profilis saswavlo programebis ganaxlebis aucileblobas. mati azrit, am amocanis realizaciisatvis sawiroa yvela dainteresebuli mxaris TanamSromloba (dawesebuleba, organizacia, sawarmo), rogorc adgilobriv, aseve saertasoriso doneze w. saertasoriso farmacevtulma federaciam SeimuSava farmacevtuli momsaxurebis standartebi saxelwodebit - `kargi farmacevtuli praqtika sazogadoebriv da saavadmyofo aftiaqebsi~, igi gansaxilvelad waredgina 1993 w. janmo-s eqspertebs, romlebmac daadasrturesdsisworeze da daamtkices 1994 w wlidan jandacvis msoflio organizaciis evropis regionalur biurosi (kopenhageni. dania) centraluri da armosavlet evropisatvis amoqmedda specialuri farmacevtuli programa, romlis mizani iyo daxmareba gaewios yofil socialistur qveynebs w. saertasoriso farmacevtuli federaciis (FIP Federation International Pharmaceutique), mier SemuSavda farmacevtuli servisis xarisxis standarti (Standards for quality of pharmacy services), romlis safuzvelzec jandacvis msoflio organizaciam SeimuSava kargi farmacevtuli praqtika Good pharmacy practice (GPP). igi Tavis mxriv warmoadgens profesiuli amocanebis CamonaTvals, romelta ganxorcielebac emsaxureba pacientebis interesebs w. tokios yrilobis Sedegebi jandacvis msoflio ansambleis mier ganxilil iqna 1994 w. janmo-s umarles saertasoriso forumze. ansambleis rezoluciis preambula (janmo , maisi 1994 w.) Seicavs umtavres daskvnebs, rom `farmacevts SeuZlia iyos mnisvnelovani specialisti jandacvis sistemasi~. janmo-s rezoluciasi dasabutebulia farmacevtebis monawileobis aucilebloba dadgenilebebisa da wesebis SemuSavebaSi, romlebic aregulireben farmacevtul saqmianobebs. janmo-s wevr qveynebs moewodat ganesazrvrat farmacevtis roli jandacvis sistemis yvela doneze, gansakutarebit nacionaluri politikis SemuSavebaSi. formulirebul iqna farmacevtuli daxmarebis koncefcia, romlis mixedvitac farmacevtis saqmianoba mtlianad orientirdeba pacientze. konferenciebis monawileta 174

175 azrit, farmacevtuli daxmareba moiazreba ara mxolod pacientebze mimartebasi, aramed mtel sazogadoebaze. farmacevtuli daxmareba moicavs: - pacients miewodos sarwmuno da obieqturi informacia preparatze; - monawileobdnen s/sasualebebze sakanonmdeblo da mareglamentirebeli motxovnebis proeqtebis SemuSavebaSi. - SeimuSaon metoduri mititebebi da kriteriumebi farmakologiuri formularebis Sesadgenad. konferenciis monawileni farmacevtul daxmarebas ganixilavdnen, rogorc GPP Semadgenel nawils. mati azrit, farmacevtis movaleobaa sando urtiertobebi daamyaros pacienttan da rekomendireba gauwios maralxarisxian medikamentebs, aseve itanamsromlos jandacvis organizaciis sxva TanamSromlebTan, saxelmwifo da sazogadoebriv organizaciebtan, farmacevtuli warmoebis warmomadgenlebtan da sxva w. daniasi, kopenhagensi jandacvis origanizaciis eqspertebis mier standartebis safuzvelze SemuSavebul iqna dokumenti `kargi farmacevtuli praqtika axal damoukidebel (ganvitarebad) qveynebsi. standartebis SemuSaveba da danergvis saxelmzrvanelo~, es rekomendaciebi gankutvnilia im qveynebistvis, romlebic imyofebian ekonomikuri ganvitarebis gardamaval etapze. dokumentsi moyvanilia aftiaqebis praqtikuli saqminobis analizi, janmrtelobis dacvasa da daavadebata profilaqtikasi farmacevtta sapasuxismgeblo sakitxebi, receptita da ureceptod gasacemi preparatebit mosaxleobis uzrunvelyofa, wamalta gamoyenebaze kontroli da metodikebi satanado farmacevtuli praqtikis etapobrivi danergvisatvis. kargi farmacevtuli praqtikis arsis mixedvit, msoflio jandacvis eqspertebi gvtavazoben, rom standartis motxovnebi dainergos qveynis nacionaluri standartis mixedvit, romelsic unda reglamentirdes evropuli nacionaluri standartebis iseti ZiriTadi motxovnebi. rogoricaa: - recepturuli medikamentebis monacemebi (Cveneba, dozireba, ukucveneba, gverditi movlenebi), romlebzec informirebulebi arian farmacevtebi; - samkurnalo sasualebebze formularebis momzadeba; - samedicino da farmacevtul praqtikasi wamalta gamoyenebaze monacemta analizis Sefaseba; - jandacvis organos TanamSromelTaTvis specialuri saganmanatleblo programis SemuSaveba da realizacia; - sareklamo kampaniebisa da sainformacio sasualebeis sakitxebi; - calkeul pacientebze monacemta konfidencialobis dacvis politika. kargi (satanado) farmacevtuli praqtika unda moicavdes Tanamedrove mdgomareobis yvela monacems da aspeqts, romelic dakavsirebulia farmacevtis roltan medikamentebis gamowerisa da moxmarebis sakitxebsi. GPP wesebi vrceldeba s/sasualebebis sacalo gacemaze da ZiriTadad warmoadgens farmacevtuli daxmarebis realizaciss koncefcias. amastanave farmacevtis profesiul saqmianobasi ZiriTadi mimartulebaa aramxolod medikamentebisa da samedicino danisnulebis sagnebis gacema, aramed kvalificiuri konsultacia da informaciis gacema samkurnalo sasualebebze. aseve farmacevtuli saqmianobis ganuyofeli nawilia maralefeqturi da xarisxiani medikamentebis racionaluri danisnulebis propaganda. arsebuli rekomendaciebis safuzvelze evropis qveynebsi gacilebit gaizarda motxovna s/sasualebata usafrtxoobaze, efeqturobasa da rentabelobaze. amisatvis Seiqmna e.w. 175

176 s/sasualebebisa da Terapiis komitetebi, sadac sxvadasxva profilis specialistebi, kerzod farmacevtebi farmakolog klinicistebtan da eqimebtan ertad SeimuSaveben samkurnalo preparatebis gamoyenebis politikas, farmakologiur formularebs, daavadebebis mkurnalobis sqemebs, romlebic garantias izlevian mkurnalobis safrtxoebasa da efeqturobaze, aseve ekonomikur-racionalur gamoyenebaze. Tavadapirvelad es xdeboda mxolod saavadmyofos doneze, romelic mizanmimartuli iyo mkurnalobis xarjebis minimizaciaze. mag. didi britanetis ert-ert saavadmyofos biujetsi antimikrobul preparatebze xarjebis matebam 10%-dan 15%-mde, aucilebeli gaxada sakitxi ganexilat ara mxolod erti saavadmyofos doneze, aramed mteli regionis doneze. mag. SotlandiaSi arnisnuli komitetebi TanamSromloben nacionalur doneze, rac arwerilia qveynis ganvitarebis nacionalur konsorciumsi, romlic CarCoebSi klinicist farmacevtebi monawileoben wamalt politikis SemuSavebaSi. konsorciumi miznad isaxavs Semcirdes klinikur kvlevaze zedmeti Zalisxmevis dublireba da nacionalur masstabebsi axal preparatebze xelmisawvdomobis uzrunvelyofa. evropis umravles qveyanasi Seqmnilia analogiuri komitetebi, romelta mizania Semcirdes hospitalizaciis xangrzlivoba, pacientis erti ganyofilebidan meoresi gadayvana, Sesabamisad gaizardos ertdriani hospitalizaciis raodenoba. arnisnuli faqti zrdis pirveladi daxmarebis rols, rogoc eqimis, aseve farmacevtis. did britanetsi amas xeli Seuwyo saxelmwifo politikam, romelic pacientis momsaxurebis miznit itxovda jandacvis sistemis gaumjobesebas, rac moiazrebda pacientis mkurnalobis, momsaxurebis uwyvet process. didi britanetis jandacvis sistemasi SemuSavda politika `samkurnalo sasualebebis optimaluri gamoyeneba~. rac Tavis mxriv zegavlenas axdenda mkurnalobis processi farmacevtis rolis mnisvnelobaze mis profesiul rcevasa da dakvirvebaze. drota ganmavlobasi gaizarda motxovna preparatebis damatebit informaciaze, ris sapasuxod farmacevtulma momsaxurebam gadainacvla saavadmyofos palatebsi.aevropis analogiurad ass qveynebsi farmacevtulma momsaxurebam miiro axali saxe farmacevt klinicistis, farmacevt laborantis saxit. isetma sakitxebma, rogoricaa Seyvanili dozis dasazusteblad sxvadasxva nivtierebebis koncentraciis garkveva sisxlis plazmasi (preparatis donis monitoringi), preparatebis urtiertqmedeba, samkurnalwamlo Terapiis gartuleba, preparatis mirebis sirtuleebi da mati Seyvanis gzebi, gverditi movlenebis Sedegad gamovlenili reaqciebi, romelic SesaZelebelia iyos sxva daavadebis simptomebi, aseve danisnulebis zusti dacva da sxva sakitxebis gadawyvetam kidev ufro daaxlova farmacevti eqimis funqciebtan. arnisnulma amerikulma modelma mnisvnelovnad gazarda farmacevtis funqciuri roli pacientis mkurnalobasi. Aam modelma ganvitareba hpova did britanetsi, CrdiloeT amerikasi, avstraliasi, axal zelandiasi, germaniasa da safrangetsi. Sesabamisad cvlileba ganicada farmacevtulma umarlesi ganatlebis programam, sadac axali disciplinis saxit daemata kinikuri farmacia. evropul-amerikuli modelebi aertianeben farmacevtis funqcias ara mxolod aftiaqis, aramed saavadmyofos doneze, iqmneba safuzveli Seiqmnas mecnierulad dasabutebuli farmakologiuri formularebi, mkurnalobis sqemebi, romlebic mnisvnelovnad amcirebs mkurnalobasi mosalodnel riskebs. GPP rekomendaciebidan gamomdinare koncefcia farmacevtuli daxmareba isazrvreba rogorc aftiaqsi, aseve saavadmyofosi da miznad isaxavs gaaumjobesos mkurnalobis Sedegebi samkurnalwamlo Terapiis xarisxze dakvirvebis sasualebit. is arwers metodebs, romelic uzrunvelyofs xarisxian, usafrtxo da efeqtur samkurnalwamlo Terapias. 176

177 aftiaqis socialuri da zogadad funqciuri rolis gafartoebas saboloo jamsi mivyavart samedicino Secdomebis Semcirebisken. kerzod, statistikurad cnobilia, w. ass-si samedicino Secdomebis Sedegad sikvdilianobis ricxvi gaizarda 27%-iT, romelmac gadaawarba sikvdilianobis sxva mizezebs (Phillips and Bredder 2002). kvlevebi adastureben, rom yvelaze gavrcelebuli mizezi iyo ojaxis eqimebis danisnuleba (Dovey at al. 2003). aseve ass-s ert-ert klinikasi Catarebulma kvlevam cxadyo, rom yovel 1000 samedicino danisnulebasi ikveteboda otxi Secdoma, aqedan 70% SeeZlo seriozuli janmrtelobis zianis gamowveva (Lesar et al. 1997). amavdroulad ass-s wamyvan klinikebsi ikveteboda pacientta hospitalizaciis xangrzlivobis zrda daaxloebit 8-12 dremde, ris mtavar mizezad saxeldeboda preparatebis gverditi movlenebis gautvaliswinebloba. Aaqedan pacientta 2-7% gamouvlinda preparatebze reaqciebi, romlis Tavidan acileba mkurnalobis dasawyissive iyo SesaZlebeli (Kohn et al. 2000). did britanetsi Catarebul kvlevebsic fiqsirdeboda analogiuri Sedegebi. Mmag erterti kvlevis mixedvit, samedicino danisnulebasi fiqsirdeboda Secdomebis 49% (Taxis and Baber 2003). rac ZiriTadad ganpirobebuli iyo administraciuli da samecniero cdomilebebit, preparatze araswori informirebulobit, mkurnalobis kursidan gadaxvevit, mkurnalobis anazraurebis sirtulit da mravali sxva (Dovey et al. 2002). ideam farmacevtuli daxmareba situacia mnisvnelovnad Secvala (Cipolle et al. 1998, 2004), ris Sedegadac transformirda farmacevtis tradiciuli roli, ramac Seamcira samedicino danisnulebasi Secdomebis raodenoba, aseve pacientta ganmeorebiti hospitalizaciis riskic. farmacevtebis kvalificiuri momsaxureba sawiro gaxda ara mxolod aftiaqebsi, aramed ambulatoriebsic rogorc pacientebistvis, aseve eqimebistvis. amgvarad, farmacevts unda hqondes SesaZlebloba monawileobdes iseti sakitxebis gadawyvetasi, romlebic exeba samkurnalo sasualebebis gamoyenebas, TanamSromlobdes jandacvis musakebtan. eqimebtan unda hqondes urtiertndobaze dafuznebuli partnioruli damokidebuleba. gansakutrebit iset sakitxebsi, rogoricaa farmakoterapia. farmacevt-klinicistebis monawileoba mnisvnelovania mkurnalobis algoritmis Seqmnis yvela etapze. farmacevt-klinicistma monawileoba unda miiros samkurnalo preparatebis gamoyenebis politikis CamoyalibebaSi, itanamsromlos profesionalebtan ama Tu im daavadebebis mkurnalobis Sesaxeb metoduri rekomendaciebisa da saxelmzrvaneloebis SemuSavebis kutxit, monawileoba unda miiros samkurnalo sasualebebis ganawilebisa da Sesyidvis, samkurnalo formularebis Seqmnis da a.s. procesebsi. saqartvelosi didi xania saubaria klinikuri farmacevtis institutis Camoyalibebaze. magaram rogorc scans menejmentis infrastruqturis inerciis gamo igi formalurad, jerjerobit ver Seiqmna. (2009 wlis aprilis monacemebi). SeniSvna: saqartvelosi daiwyo gaidlainebis momzadeba. samwuxarod, verc erti gaidlainis saavtoro jgufsi jerjerobit ver SevamCnieT farmacevti. vfiqrobt, gaidlainebis momzadebis processi ukve aucilebelia farmacevt-klinicistis monawileoba. amave dros, samedicino, mat Soris farmacevtuli infraqstruqtura saqartvelosi swrafad vitardeba da Tamamad SeiZleba itqvas farmacevtta nawili praqtikam aizula Tavis Tavze aero es funqcia realurad (funqcionalurad) kliniuri farmacevtis instituti cxovrebam Camoayaliba. mag. Ddidi farmacevtuli firmebis farmacevtebi (farmacevtuli kompania PSP) arc Tu isviatad izulebulni arian konsultacia gauwion pacientebs, sadazrvevo kompaniebis farmacevt-konsultantebic faqtiurad klinikuri farmacevtis funqcias asruleben. 177

178 klinikuri farmacia, rogorc avrnisnet, integrirebuli mecnierebaa. Mmisi ert-erti damaxasiatebeli da momijnave samedicino dargebidan ganmasxavebeli nisania integrireba sainformacio teqnologiebis (matematikur, sainjinro) mecnierebebtan. klinikuri farmaciis swavleba saxelmwifo samedicino universitetis farmacevtul fakultetze daaxloebit 10 welia mimdinareobs. mirebulia gadawyvetileba am ganxrit magistrebis momzadebis Sesaxeb, magram, samwuxarod, am specialobit magistraturasi mireba ar ganxorcielebula. jer kidev 2007 wels saqartvelosi daaxloebit 5400 preparati iyo registrirebuli, mati raodenoba swrafad izrdeba. Bbevrad metia preparatta raodenoba ekonomikurad ganvitarebul qveynebsi. Bbunebrivia, am moculobis informaciastan manipulireba, SedarebiTi analizis gaketeba, SeuZlebelia specializebuli sainformacio sistemebis garese, rac moitxovs dasaxelebuli mecnierebebis ara marto gamoyenebas, aramed mattan integrirebas, amistvis aucilebelia: -Ffarmacevtis ganatlebasi klinikuri mecnierebebis ufro fartod Setana. - mkurnali eqimebisatvis klinikuri farmacevtebis SesaZleblobebisa da funqciebis gacnoba. -Aamoqmeddes receptebis instituti; -Aamoqmeddes farmacevtta specializebuli sainformacio sistemebi; -Ddaarsdes wamlis xarisxis kontrolis saarbitrajo laboratoria; - Sesabamisad unda iqnas gamoyenebuli farmacevtis potenciali, rogorc marketologis, romelmac Sesabamisad unda Seasrulos eqspertis roli momxmarebelta mxridan samkurnalo preparatebis motxovnis, xarisxis, fasebis, SefuTvisa da a.s. SefasebaSi. unda gamoikvlios bazris nisa, SeimuSaos axali produqti, ganaxorcielos sareklamosainformacio samusaoebi samamulo warmoebis medikamantebze, Seagrovos da ganavrcos preparatebze klinikuri monacemebi, aseve Seiswavlos momxmarebelta reaqcia axali preparatebis danergvisas. -Uunda arsebobdes bazris kvlevisa da marketinguli jgufebis sainformacio baza. -Aamoqmeddes wamlis gverditi movlenebis monitoringis samsaxuri (Pharmacorigilance). literatura 1. American Society of Health System Pharmacists. Guidelines on Standardized Method for Pharmaceutical Care 1996; 53: Bates DW. Using information technology to reduce rates of medication errors in hospitals, British Medical Journal 2000; 320: Bond C.A., Raehl C.L., Franke T. Clinical pharmacy services, hospital pharmacy staffing, and medication errors in United States hospitals. Pharmacotherapy 2002; 22: Brackenborough S. Views of patients, general practitioners and community pharmacists on medicines-related discharge information. The Pharmaceutical Journal 1997; 259: Burns J.M.A., Sneddon I., Lovell M., MacLean A., Martin B.J. Elderly patients and their medication: a postdischarge follow-up study. Age and Ageing 1992; 21: The Role of the Pharmacist in the Health Care System. Report of a WHO Consultative Group New Delhi December Geneva: 1990; Good Pharmacy Practice in Community and of Hospital Pharmacy Settings. World Health Organization: The Individual and Health Care: Added value through Self-medication. AESGP. Brussels: SUMMARY GOOD PHARMACY PRACTICE (GPP) THE CREATION AND DEVELOPMENT Chanturia Z. Tbilisi State Medical University, Department of Social and Clinical Pharmacy, Georgia 178

179 XX century in the world pharmaceutical market is strong and growing conglomerate of manufacturing and selling of drugs. International intelligence company IMS Health Consulting 2012 sec. According to the World Pharmaceutical Market volume totaled $ 940 billion. There was an increase of 6% compared to previous years. Experts predict the near future as the growing trend of 3-4% up. The last decade has led to a growing demand for drastic changes in the structure of the pharmaceutical market, which has increased demand for its services and the pharmacist. The World Health Organization (WHO) experts showed an active interest in the role of the pharmacist in the last century 80 - ies. It is notable that the interest of the medical services in the field of functional reduction pharmacist. The initiator of a professional association - the International Pharmaceutical Federation (FIP - Federation International Pharmaceutique). According to the participants, not only thinks of pharmaceutical care to patients, but also - for the whole society. Naturally, this volume of information manipulation, comparative analysis, it is impossible without specialized information systems, which requires not only the use of the aforementioned studies, but also to integrate them. For this purpose it is necessary: - clinical pharmacist education in the sciences more broadly. - Medicare physicians for the clinical pharmacist's capabilities and functions. - prescription enacted Institute; - enacted Pharmacists specialized information systems; - Establishment of Drug Quality Control Laboratory of the arbitration; - must be used in accordance with the pharmacist's potential as a marketer. According to the expert's role to be played by consumers who demand drugs, quality, price, packing, etc. Assessment. To explore niche markets, develop new products, carry advertising - media jobs, domestic production of medicines, collect and ganarvtsos drug clinical trial data, as well as exploring users' reactions to the implementation of a new drug. - There should be a market research and database marketing groups. - To be effective monitoring of drug side effects (Pharmacorigilance). SEVERE SKIN REACTIONS AFTER PEMETREXED TREATMENT: A RETROSPECTIVE STUDY 1 Capelle H., 2 Greillierr L., 3 Tummino C., 3 Gouitaa M., 1 Ausias N., 4 Rathelot P., 2 Barlesi F., 1-4 Montana M. 1 Oncopharma, Hôpital Nord, AP-HM, Marseille, France; 2 Aix Marseille Université; Assistance Publique Hôpitaux de Marseille.Oncologie multidisciplinaire et innovations thérapeutiques, Marseille, France; 3 Service de Pneumologie, Hôpital Nord, AP-HM, Marseille, France; 4 Aix-Marseille Université, CNRS, Institut de Chimie Radicalaire ICR, UMR 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Marseille, France Pemetrexed (PEM), a multitargeted antifolate drug, is approved in combination with cisplatin, for first-line medical treatment of advanced or metastatic non-squamous non-small cell lung cancer. This molecule is usually well tolerated but cutaneous adverse reactions (CAR) are reported [1-3]. The aim of this study was to determine the frequency and clinical characteristics of severe CAR due to the administration of PEM. Materiel and method. A retrospective study was conducted at Nord Teaching Hospital (AP-HM) between June 2010 and July Medical data of patients experimenting severe CAR were analyzed to bring out clinical aspects 179

180 of CAR. With CHIMIO software, age, sex, chemotherapy treatments, premedication and cumulative PEM dose of these patients were noted. Results and discussion. During this period, 735 patients were treated with PEM. Among them, 10 (9 men and 1 woman) experimented a severe CAR. Mean age was 67.6 years and mean cumulative PEM dose was mg when the CAR occurred. None of the 10 patients had a specific anti-allergic premedication. Several polymorphic forms of CAR had been diagnosed: 5 pruritus, 3 erythema, 2 urticarial rash and 1 bullous skin denudation. CAR concerned face (1 case), legs (1), trunk (2) or were generalized (5). 6 patients developed a CAR at the first cure of PEM, 2 at cure number 4, 1 at cure number 10 and 1 at cure number 22. In order to determine the cause of this event, allergy assessments were conducted. Intradermal skin tests (dilutions used: 1/10,000; 1/1,000; 1/100 et 1/10) were negative to PEM for 9 patients and 1 test remained unclear. PEM-related CAR are frequently reported under the unspecific "skin rash" term. Cutaneous toxicity of all grades has been observed in up to 14%, and grade 3 or 4 toxicity in % of cases [1]. In our study, severe CAR are described for 1.36% of patients treated with PEM. Only 1 bullous skin toxicity was observed, confirming that severe skin reactions after PEM administration are rare, such symptoms should alert physicians to subsequent potentially more severe CAR. To the best of our knowledge, it is the first description of PEM intradermal skin testing. The benefit of these tests, well documented for other anticancer drugs like platinum salts, remains unclear for PEM, maybe because the origin of CAR is attributed to direct cytotoxicity of PEM [3]. Conclusion: The appearance of skin lesions is an indication for careful follow-up and clinicians must be warranted for the possibility of Lyell's syndrome. REFERENCES 1. Tummino C, Barlesi F, Tchouhadjian C. et al. Severe cutaneous toxicity after Pemetrexed as second line treatment for a refractory non small cell lung cancer Rev Mal Respir. 2007;24(5): Lopes G, Vincek V, Raez LE, Pemetrexed-associated urticarial vasculitis. Lung Cancer 2006;51: Piérard-Franchimont C, Quatresooz P, Reginster MA. et al. Revisiting cutaneous adverse reactions to pemetrexed Oncol Lett 2011;2(5): THE STUDY OF CHEMICAL COMPOSITION OF POLYGONUM AMPHIBIUM Shevchenko A., Muzychkina R., Korulkin D. Faculty of Chemistry and Chemical Technology, al-farabi Kazakh National University As a part of our ongoing phytochemical investigation of plants from Polygonum genus (Polygonaceae), we investigated the chemical composition of Polygonum amphibium collected on Pervomay Lake in Almaty, Kazakhstan. Plants from this genus are used in traditional medicine, diet, and as ornamental plants [1]. Phytochemical analysis showed the presence of flavonoids (1,75%), triterpene saponins (0,78%), coumarins (0,33%), tannins (2,37%) and polysaccharides (4,46%) in its composition, Their quantification was held according to the methods of State Pharmacopoeia of the Republic of Kazakhstan [2]. Were isolated and identified by TLC and PC individual components from herb of Polygonum amphibium L. Flavonoids (quercetin and quercetin glycosides in addition to isorhamnetin), triterpenoid saponins (hederagenin, oleanolic acid), phenolic acids (caffeic acid, cinnamic acid), phenols (catechol, pyrogallol) from ethanolic extract. 180

181 OH OH HO O OH HO O O CH 3 OH O Quercetin OH OH O OH Isorhamnetin Previously reported in the literature about the manifestation of antileukemic activity of two new flavonoid glucuronides, quercetin-3-o-β-glucuronide and quercetin-3-o-α-rhamnosyl-(1 2) -β-glucuronide, and kaempferol-3-o-α-rhamnosyl-(1 2) -β-glucuronide, were isolated from Polygonum amphibium L. It was demonstrated that the glucuronides of quercetin are able to induce apoptosis in the tested human leukaemic cells. These compounds penetrate through cytoplasm to the cellular nucleus of the cultured cells, and give intensive apoptotic responses in the stimulated leukaemic cells [3]. REFERENCES 1. Pavlov N.V. Flora of Kazakhstan. Alma-Ata: Academy of Sciences of the USSR: 1961; State Pharmacopoeia of the Republic of Kazakhstan. Almaty: Publishing House "Silk Joly.": 2008; Smolarz H.D., Budzianowski J., Bogucka-Kocka A., Kocki J., Mendyk E., Flavonoid glucuronides with antileukaemic activity from Polygonum amphibium L. Phytochem. Analysis 2008; THE STUDY OF COUMARIN QUANTITATIVE CONTENT IN THE RAW MATERIALS OF PLANTS FROM THE CELERY FAMILY Ternynko I. Department of Pharmaceutical Chemistry and Pharmacognosy, SI Lugansk State Medical University, Lugansk,Ukraine Coumarins - class of phenolic compounds which have specific pharmacological activity and are selectively localized in the raw materials of plant belonging the Celery family. Among the compounds of this class are devote the most attention to the furcoumarins and their plant sources, because they exhibit antispasmodic activity and are used in nephrology and cardio - vascular diseases [1-3]. In the mid of the 20th century Ukrainian phytochemists investigated content of the coumarin in the fruit of the Celery family [4]. However, the study of other raw materials of these plants for the accumulation of coumarin was not conducted. Herb of the plants of the Celery family has a significant and rapidly recovering phytomass, because the plants are used as spice - aromatic crops [5]. Therefore the aim of the work was to study the content of coumarin in raw materials (grass and fruit) plants of the Celery in a comparative perspective to predict the use of alternative sources of raw materials of this group of BAS. As objects of study used the grass and fruit of dill (g.d., f.d.) (Anaethum graveolens L.), fennel (g.f., f.f.) (Foeniculum vulgare Mill.), coriander (g.cor., f.cor.) (Coriandrum sativum L.), fruit of the caraway (f.car.) (Carum carvi L.) and anise (f.a.) (Anisum vulgare Gaertn.), grass (g.c.) and celery root (r.c.) (Apium graveolens L.). Detection was spend with used of spectrophotometric method in terms of umbelliferone by determining the optical density of the colored complex coumarins with diazotized sulfanilic acid [6]. The study found that the coumarin prevail in fruit of plant from the Celery family: f.d. 0,12,%; g.d.. 0,05 %, f.f. 0,09 %,g.f. 0,05 %; f.cor. 0,07 %, g.cor. 0,04 %; f.car. 0,11%, f.a. 0,13 %, r.c. and g.c. 0,08 %. The 181

182 coumarin source for phytopreparations can be anise fruits (0,13 %), caraway fruits (0,11 %) and fennel fruits (0,12 %). Additionally, it was determined the content of coumarin in umbels of fennel, which remains after the separation of the fruit. Coumarin content in them is 0,11 %, which allows us to recommend umbrellas as an alternative source of this group of BAS and enables more efficient use of the whole plant. REFERENCES 1. Кузнецова Г.А. Природніе кумарині и фукрокумарині. Л.: Наука: 1967; Kovac-Besović E.E., Durić K. Thin layer chromatography-application in qualitative analysis on presence of coumarins and flavonoids in plant material. Bosn. J. Basic. Med. 2003; 3(3): Peter K.V. Handbook of herbs and spices. Cambridge: Woodhead Publishing Ltd,. 2. Аccess mode: Георгиевский В.П., Комиссаренко Н.Ф., Дмитрук С.Е. Биологически активные вещества лекарственных растений. Новосибирск: Наука: 1990; Коршиков Б.М. и др. Лекарственные свойства сельскохозяйственных растений. Под ред. М.И. Борисова, С.Я.Соколова. 2-е изд., перераб. и доп. Мн.: Ураджай: 1985; Ярошенко І.В. Фітохімічне вивчення рослин роду Orchis та розробка рослинних зборів для корекції надмірної ваги. Aвтореф. дисc... на здобуття наук. ступ. канд. фармац. наук. Х.: 2010; 20. ornidazolis (gerali) tabletebis standartis damusaveba TuTberiZe n., WumburiZe b., lasauri n., ioramasvili h., jorjikia m. farmacevtuli sawarmo GGMP-is xarisxis uzrunvelyofis laboratoria, Tbilisis saxelmwifo samedicino universiteti, farmacevtuli da toqsikologiuri qimiis departamenti, saqartvelo 5-nitroimidazolis nawarmebi moqmedebis farto speqtris maralaqtiuri antimikrobuli naertebia, romlebic gamoiyeneba anaerobuli baqteriebit da zogierti umartivesit gamowveuli infeqciuri daavadebebis samkurnalod. es naertebi aqtiuria agretve fakultatiuri anaerobebis (mikroaerofilebis) mimart. qimiuri struqturit, 5- nitroimidazolebi sintezuri dabalmolekuluri naertebia, romlebic imidazolis ciklis me-5 mdgomareobasi Seicaven nitrojgufs (NO 2 ). marali antimikrobuli da optimaluri farmakologiuri da toqsikologiuri Tvisebebis gatvaliswinebit, samedicino praqtikasi gansakutrebit fartod gamoiyeneba 5-nitroimidazolis nawarmi sami preparati: metronidazoli, tinidazoli da ornidazoli. mat garda medicinasi iyeneben: seknidazols, nimorazols, ternidazols, satranidazols da zogiert sxva samkurnalo sasualebas. ornidazoli-1-qlor-3-(2-metil-5-nitroimidazol-1-il)propan-2-oli aris moyvitalo- TeTri feris mikrokristaluri fxvnili. ornidazoli xsnadia wyalsi, etersi, etanolsa da qloroformsi. nax. 1. ornidazolis qimiuri struqtura 182

183 kvlevis masala da metodebi. kvlevis masalas warmoadgenda ornidazolis substancia, ornidazolis Semcveli preparati «gerali» da misi analogi tiberali. kvlevisatvis gamoyenebuli iqna analizis metodebi: fizikuri metodebi tabletebis sasualo masis, xsnadobis, dasladobis gansazrvrisatvis, maralefeqturi sitxuri qromatografia moqmed nivtierebasi da tabletebsi ornidazolis raodenobrivi gansazrvristvis, tabletebsi xsnadobisa da garese minarevebis gansazrvrisatvis, infrawiteli speqtrofotometria moqmedi nivtierebis identifikaciisa da sisuftavis gansazrvrisatvis. eqsperimentuli nawili: ornidazolis igiveobisa da raodenobrivi gansazrvris analizi vawarmoet maralefeqturi sitxuri qromatografiit. moqmedi nivtierebis identifikaciistvis gamoviyenet infrawiteli speqtrofotometria. wylis Semcveloba ganvsazrvret karl-fiseris metodit. nax. 2. standartuli nimusis qromatograma nax. 3. sakvlevi nimusis qromatograma sakvlevi da standartuli nimusis pikis Sekavebis dro aris identuri. ornidazolis Semcveli tabletebis geralis analizi: geralsi ganvsazrvret: preparatis sasualo masa, igiveoba da raodenoba, xsnadoba, garese minarevebi. tabletis sasualo masa (20 tabletidan) mirebuli Sedegi 0,6647 g; Nnorma g; masidan gadaxra %; norma - ± 5.0 %. geralis identifikacia da raodenobrivi gansazrvra vawarmoet maralefeqturi sitxuri qromatografiuli metodit. maralefeqturi sitxuri qromatografis injeqtorsi cal-calke movaxdinet standartuli da sakvlevi xsnarebis inicireba da CaviwereT pikebi. ornidazolis raodenobrivi Semcveloba geralis tabletebsi armocnda mg (norman mg). 183

184 geralis tabletebsi ornidazolis xsnadobis gansazrvra vawarmoet maralefeqturi sitxuri qromatografiuli metodit. xsnadobis pirobebi: gamxsneli are: 900,0 ml 0,1 NHClL temperatura: 37±0,5 C; brunvis sicqare br/wt; dro - 30 wuti geralis tabletebsi ornidazolis xsnadoba armocnda % (norma aranakleb 75%).,,geralSi ornidazolis garese minarevebis raodenobrivi Semcveloba ganvsazrvret maralefeqturi sitxuri qromatografiuli metodit. garese minarevebis raodenobrivi Semcveloba geralis tabletebsi ganisazrvra maralefeqturi sitxuri qromatografiuli metodit (2-meTil-5-nitroimidazolis Semcveloba %, minarevebis jamuri Semcveloba %). geralis da misi analogis - tiberalis gamotavisuflebis Sedareba: eqsperimentulad ganisazrvra geralisa da misi analogis tiberalis gamotavisuflebis xarisxi. geralis gamotavisuflebis sasualo procentuli mnisvnelobaa %; tiberalis %. sxvaoba aris 1.49% (norma ±5%). mirebuli SedegebiT, gerali xasiatdeba kargi gamotavisuflebis xarisxit. reziume ornidazolis (gerali) tabletebis standartis damusaveba TuTberiZe n., WumburiZe b., lasauri n., ioramasvili h., jorjikia m. farmacevtuli sawarmo GGMP-is xarisxis uzrunvelyofis laboratoria, Tsbilisis saxelmwifo samedicino universiteti, farmacevtuli da toqsikologiuri qimiis departamenti, saqartvelo Catarebuli iqna ornidazolis analizi maralefeqturi sitxuri qromatografiuli metodit. raodenobrivi Semcveloba aris 99.97%. axlad atvisebuli preparatis geralis tabletebis sasualo masa aris 0,6647 g. praqtikulad mirebuli sasualo masidan gadaxra aris 0.79%, rac normis farglebsia. geralis tabletebsi ornidazolis raodenobrivi Semcveloba aris mg, rac normis farglebsia. geralis tabletebsi ornidazolis xsnadoba aris %. garese minarevebis raodenobrivi Semcveloba geralis tabletebsi ganisazrvra maralefeqturi sitxuri qromatografiuli metodit (2-meTil-5-nitroimidazolis Semcveloba aris %, minarevebis jamuri Semcveloba %), rac normis farglebsia. Sedgenili iqna droebiti farmakopeis statiis proeqti geralis 500 mgian tabletebze. eqsperimentulad ganisazrvra geralisa da misi analogis tiberalis in vitro gamotavisuflebis xarisxi. geralis gamotavisuflebis sasualo procentuli mnisvnelobaa %; tiberalis %. Catarda moqmedi nivtierebis infrawiteli speqtrofotometruli analizi. ornidazolis speqtri TanxvedraSia standartis speqtrtan. SUMMARY STANDARDITATION OF GERAL (ORNIDAZOLE) TABLETS Tutberidze N., Chumburidze B., Lashauri N., Ioramashvili H. Jorjikia M. QA Department of Georgian Pharmaceutical Manufacturing Company - GM Pharmaceutical 184

185 Tbilisi State Medical University, Department of Pharmaceutical And Toxicological Chemistry, Georgian Analyses of Ornidazole was conducted using High performance liquid chromatography (HPLC). Quantitative content was found to be 99.97%. Average Mass for newly-implemented product Geral was 0,6647g. Deviation from the average mass was 0.79%, which is within the acceptable limits. Quantitative content for finished product (tablets of Geral) was mg, which is within the acceptable limits. Dissolution of Ornidazole in Geral tablets was %. In Geral tablets High performance liquid chromatography (HPLC) was used for quantitative determination of external impurities. For "Geral" 500 mg tablets Inhouse Analytical method documentation were prepared. The level of In vitro release for Geral and its analogue medicine Tiberal was measured. The average release index for Geral was % and for Tiberal %. Infrared Spectrophotometric Analyses for Active substance was conducted and Infrared Spectrum of ornidazole was in Compliance with the spectrum of standard. literatura 1. l. datesize, a. Sengelia, v. Sengelia. qartuli samedicino enciklopedia. T.: b. WumburiZe, T. WumburiZe, T. CikvilaZe. wamalta standartizacia da xarisxis menejmenti. T.: a. bakurize, b. WumburiZe, i. moniava, r. maxaraze da sxv. farmacevtuli sawarmos normatiul-teqnikuri dokumentebis Sedgenis metoduri safuzvlebi. Tb.: 2006; saxelmwifo farmakopea. t. I. Tb.: 1998; saxelmwifo farmakopea. t. II. Tb.: 2003; Беликов В.Г. Фармацевтическая химия. М.: Puranik M., Bhawsar D.V., Rathi P., Yeole P.G. Simultaneous Determination of Ofloxacin and Ornidazole in Solid Dosage Form by RP-HPLC and HPTLC Techniques. Indian J Pharm Sci. 2010; 72(4): gluferalis tabletebsi fenobarbitalis da kofeinis raodenobrivi gansazrvris speqtrofotometruli metodis validacia baramize q., megreli n., tefnaze l., CikvilaZe T., jorjikia m. `globaltesti~-s sagamocdo laboratoria; Tbilisis saxelmwifo samedicino universiteti, farmacevtuli da toqsikologiuri qimiis departamenti, saqartvelo saertasoriso xarisxis (ISO 17025) standartis motxovnis Sesabamisad, samkurnalo sasualebebis normatiul-teqnikur dokumentaciasi (ntd) mocemuli, moqmedi nivtierebebis raodenobrivi gansazrvris metodebi unda iyos validirebuli ICH Q 2 A (CPMP/ICH/381/95). validacia, es aris imisi eqsperimentaluri dadastureba, rom metodika vargisia mocemuli davalebis gadasawrelad (1,6,7). ICH izleva rekomendacias, eqsperimenti ise daigegmos, rom raodenobrivi gansazrvris metodis validacia ertdroulad Catardes Semdegi validaciis maxasiateblebis mixedvit: stabiluroba, specifiuroba, sworxazovneba, sizuste da siswore. amastan unda arinisnos, rom kriteriumebis sistematiuri gamoyeneba, romelic itvaliswinebs samkurnalo sasualebebis specifikas, 185

186 sxvadasxva mizezis gamo samecniero literaturasi isviatad gvxvdeba [2,3]. rac iwvevs garkveul sizneleebs rogorc ntd-s SemmuSaveblebSi, aseve mwarmoeblebsi, saregistracio dosies Sedgenisas. gansakutrebit mwvaved dgas mocemuli problema im mwarmoeblebis winase, romlebic gadadian GMP-s motxovnebze, radgan analizuri metodikebis validacia GMP-s aucilebeli motxovnaa [1,2,4,5]. nasromis mizani: `Tbilqimfarmi~-s (saqartvelo) nawarmi samkurnalo sasualebis, gluferalis tabletebsi fenobarbitalis da kofeinis raodenobrivi gansazrvris sfeqtrofotometruli metodis validacia. kvlevis masala da metodebi. kvleva ganxorcielda xarisxis saertasoriso standartebis (ISO 17025, ICH Q 2 A) motxovnebis Sesabamisad, Semdegi validaciis maxasiateblebis mixedvit: stabiluroba, specifiuroba, sworxazovneba, sizuste da siswore. orive aqtiuri komponentis raodenobrivi analizi ganxorcielda speqtrofotometruli metodit, 220-dan 280 nm STanTqmis diapazonsi, ramac mogvca ertdrouli validaciis Catarebis SesaZlebloba. kvlevas vawarmoebdit xelsawyoze SPECORD-40, romlis teqnikuri da saeqsploatacio maxasiateblebi mtlianad Seesabameba ass, britanetis da evropis farmakopeebis motxovnebs da damowmebulia ssip `standartebis, teqnikuri reglamentebisa da metrologiis erovnuli saagento~-s mier. eqsperimentuli nawili: gamyof ZabrSi vatavsebdit 30 ml 0,1 mol natriumis hidroqsidis xsnars, daaxloebit 0,2 g (zusti wona) dafxvnil tabletebs, 30 ml qloroforms da vanjrrevdit 3 wt-is ganmavlobasi. gansrevebis Semdeg qloroformian gamonawvlils vatavsebdit sxva gamyof ZabrSi. wyliani fazis eqstragirebas vaxdendit 20 ml qloroformit samjer, qloroformian gamonawvlilebs vagrovebdit da CavrecxavdiT 10 ml 0,1 mol natriumis hidroqsidis xsnarit. qloroformian eqstraqtebsi vsazrvravdit kofeins. tute xsnars (30 ml da 10 ml) vfiltravdit biuxneris ZabriT ormag filtrsi. gamyof Zabrs da filtrs CavrecxdiT 10 ml 0,1 mol natriumis hidroqsidis xsnarit. filtrats raodenobrivad gadagvqonda 100 ml-ian gamzom kolbsi da moculobas Wdemde vavsebdit imave gamxsnelit. mirebuli xsnaris 5 ml vatavsebdit 50 ml-ian gamzom kolbsi da Wdemde vavsebdit 0,1 mol natriumis hidroqsidis xsnarit. xsnaris optikur simkvrives vsazrvravdit speqtrofotometrulad, 255 nm sigrzis talraze, 10 mm sisqis kiuvetsi. Sesadareblad viyenebdit natriumis hidroqsidis 0,1 mol xsnars, paralelurad vsazrvravdit fenobarbitalis standartuli nimusis xsnaris optikur simkvrives. ert tabletsi fenobarbitalis Semcvelobas gramebsi (X) vitvlidit formulit: X D в D в = = D0 a 5 D0 a sadac, D 1 _ sakvlevi xsnaris optikuri simkvrivea; D 0 _ fenobarbitalis standartuli nimusis xsnaris optikuri simkvrive; 0, _ fenobarbitalis Semcveloba standartuli nimusis xsnaris 1 ml-si, g-si. a _ nimusis wonaki, g-si; b _ tabletis sasualo masa, g-si. darcenil qloroformian gamonawvlils vfiltravdit qloroformit Sesvelebul 186

187 qaraldis filtrsi, uwylo natriumis sulfatis TanaobiT 200 ml-ian gamzom kolbsi, filtrs CavrecxdiT qloroformit da Wdemde vavsebdit imave gamxsnelit. mirebuli xsnaris optikur simkvrives vsazrvravdit speqtrofotometrulad 275 nm sigrzis talraze, 10 mm sisqis kiuvetsi. Sesadareblad viyenebdit qloroforms. paralelurad vsazrvravdit kofeinis standartuli nimusis xsnaris optikur simkvrives. uwylo kofeinis Semcvelobas ert tabletsi g-si (X) vitvlidit formulit: D в 200 D в X = = D0 a D0 a sadac, D 1 _ sakvlevi xsnaris optikuri simkvrivea; D 0 _ kofeinis standartuli nimusis xsnaris optikuri simkvrive; 0, _ uwylo kofeinis Semcveloba standartuli xsnaris 1ml-Si, g-si; a _ nimusis wonaki, g-si; b _ tabletis sasualo masa, g-si. kriteriumi: fenobarbitalis (С 12 Н 12 N 2 O 3 ) Semcveloba ert tabletsi unda iyos 0,022 0,027g,Duwylo kofeinis (С 8 Н 10 N 4 O 2 ) 0,0018 0,0022 g tabletis sasualo masaze gadaangarisebit. kvlevis Sedegebi: specifiuroba fenobarbitalisa da kofeinisatvis talris sigrzeebis specifiuri sasualo mnisvneloba ganisazrvra samusao dris ganmavlobasi 6-6 standartuli nimusis da sakvlevi xsnaris sinjebis analizit. dadginda, rom fenobarbitalis da kofeinis gansazrvrisatvis specifiuria 255±1nm da 277±1nm sigrzis talrebi Sesabamisad. erti samusao dris ganmavlobasi mirebuli Sedegebis specifiurobis variaciis koeficienti Seadgenda 0,159 da 0,147. xolo samusao kviris ganmavlobasi 0,362 da 0,312 fenobarbitalis da kofeinisatvis Sesabamisad, rac miutitebs analizuri metodebis mimart wayenebuli kriteriumebis mimart metodis specifiurobis Sesabamisobaze (CV 2%). A A 0,2500 0,2500 0,2000 0,2000 0,1500 0,1500 0,1000 0,1000 0,0500 0,0500 0,0000 0, ,0 225,0 250,0 275,0 300,0 325,0 350,0 375,0 nm 200,0 225,0 250,0 275,0 300,0 nm Absorbance Absorbance nax. 1. kofeinis da fenobarbitalis standartuli nimusebis speqtrogramebi ganisazrvra agretve sistemis sizuste, romelic fenobarbitalisatvis Seadgens 0,6085%, kofeinisatvis 0,7983% (kriteriumi 2%), metodis sizuste, romelic fenobarbitalisatvis Seadgens 0,6089%, kofeinisatvis 0,3537% (kriteriumi 2%), siswore (metodis sistematiuri cdomileba), romelic fenobarbitalisatvis Seadgens 4,5548%, kofeinisatvis 1,790% (kriteriumi 5%). metodis sworxazovnebis gansazrvra Catarda eqvs sxvadasxva koncentraciis xsnarze 187

188 (80%, 90%, 100%, 110% da 120% - tabletsi fenobarbitalis da kofeinis nominaluri Semcvelobidan gamomdinare). koncentraciis miuxedavad, CV-s sidide ar aremateba 0,25%- s. korelaciis koeficienti ki Seadgens 0, fenobarbitalistvis da 0,9990-s kofeinistvis (ara umcires 0,998 kritikuli mnisvnelobis dros). amdenad, metodika sworxazovania 0,012 0,018 mg/ml diapazonsi fenobarbitalisatvis da 0,0048 0,0072 mg/ml kofeinisatvis. 0,34 Кофеин Поглощение = 0, ,8*x 0,32 0,30 Поглощение 0,28 0,26 0,24 0,22 0,20 0,0046 0,0050 0,0054 0,0058 0,0062 0,0066 0,0070 0,0074 Концентрация, 0,0048 мг/мл:поглощение: 0,0052 r 0, = 0,9990; 0,0060 r = 0,9995, p 0,0064 = 0,00001; y 0,0068 = 0, , ,8*x Концентрация, мг/мл nax. 2. kofeinis standartuli nimusis xsnarebis sakalibro grafiki (korelaciis koeficienti 0,9990) 0,30 Фенобарбитал Поглощение = 0, *x 0,28 0,26 Поглощение 0,24 0,22 0,20 0,18 0,011 0,012 0,013 0,014 0,015 0,016 0,017 0,018 0,019 Концентрация, мг/мл:поглощение: 2 r = 0,9991; Концентрация, r = 0,9995, мг/мл p = 0,00001; y = 0, *x nax. 3. fenobarbitalis standartuli nimusis xsnarebis sakalibro grafiki (korelaciis koeficienti 0,9991) SemuSavebulia arwarmoebadi, mgrznobiare, zusti da efeqturi metodi gluferalis tabletebsi fenobarbitalis da kofeinis speqtrofotometruli raodenobrivi gansazrvrisatvis; dadgenilia, rom fenobarbitalisa da kofeinis gansazrvrisatvis specifiuria 255 ± 1 нм и 277 ± 1 нм sigrzis talrebi Sesabamisad; mirebuli Sedegebi miutitebs analizuri metodebis mimart wayenebuli kriteriumebis mimart Sesabamisobaze (СV 2%); 188

189 metodis sizuste rogorc kofeinis, aseve fenobarbitalisatvis Seadgens 99%, sistematiuri cdomileba (metodis siswore) naklebia 2%-ze; yvela gansazrvrebsi korelaciis koeficienti metia 0,999-ze (ara umcires 0,998 kritikuli mnisvnelobis dros); fenobarbitalisatvis korelaciis koeficienti 0,9991-ia, kofeinisatvis 0,9990; metodika sworxazovania 0,012 0,018 mg/ml diapazonsi fenobarbitalisatvis da 0,0048 0,0072 mg/ml diapazonsi kofeinisatvis. amdenad, gluferalis tabletebsi fenobarbitalis da kofeinis raodenobrivi gansazrvris metodis validaciis Sedegad dadginda SemuSavebuli speqtrofotometruli metodis sruli Sesabamisoba Guidance for Industry Bioanalytical Method Validation U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Veterinary Medicine (CVM) May 2001-is motxovnebtan Semdegi validaciuri maxasiateblebis mixedvit: stabiluroba specifiuroba, sworxazovneba, sizuste da siswore. literatura 1. Гризодуб А.И. Фармаком 2002; 3: Гризодуб А.И., Леонтьев Д.А., Денисенко Н.Н. Фармаком 2004; 3: Лутцева А.И., Титова А.В., Боковикова Т.Н. Ведомости научного центра экспертизы и государственного контроля лекарственных средств 2001; 6: Barends M. J. Pharm. Pharmacol. 2005; 11: European Pharmacopoeia. 7 th ed. Supplement ICH Q2 A (CPMP/ICH/381/95), Validation of analytical procedure: Methodology, London UK: USP 36 NF 31 rezume gluferalis tabletebsi fenobarbitalis da kofeinis raodenobrivi gansazrvris speqtrofotometruli metodis validacia baramize q., megreli n., tefnaze l., CikvilaZe T., jorjikia m. `globaltesti~-s sagamocdo laboratoria; Tbilisis saxelmwifo samedicino universiteti, farmacevtuli da toqsikologiuri qimiis departamenti, saqartvelo gluferalis tabletebsi fenobarbitalis da kofeinis raodenobrivi gansazrvris metodis validaciis Sedegad dadginda SemuSavebuli speqtrofotometruli metodis sruli Sesabamisoba Guidance for Industry Bioanalytical Method Validation U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Veterinary Medicine (CVM) May 2001-is motxovnebtan Semdegi validaciuri maxasiateblebis mixedvit: specifiuroba, sworxazovneba, sizuste da siswore. SUMMARY VALIDATION UV QUANTITATIVE DEFINITION OF PHENOBARBITAL AND CAFFEINE IN TABLETS GLUFERAL Baramidze K., Megreli N., Tefnadze L., Chikviladze T., Jorjikia M. "Globaltest", Llc, Testing Laboratory; Tbilis State Medical Unversity, Department of Pharmaceutical and Toxicological Chemistry, Georgia 189

190 Thus, the results received during validation of an analytical method of definition of phenobarbital and caffeine in tablets Gluferal have shown full conformity of the developed method to requirements Guidance for Industry Bioanalytical Method Validation U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Veterinary Medicine (CVM) May 2001 on the following validation characteristics: Stability, Specificity, Linearity, Accuracy and precision. DETERMINATION OF POLYPHENOLS IN BETULA MEDWEDIEWII GROWING IN GEORGIA USING HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY WITH DIODE ARRAY DETECTION AND ELECTROSPRAY IONIZATION MASS SPECTROMETRY Zardiashvili L., Jokhadze M., Kuchukhidze J., Chincharadze D., Berashvili D., Bozhadze A. Tbilisi State Medical University, Department of Pharmacognosy and Botany, Georgia Well-known as birch tree, the genus Betula of the family Betulaceae, has a wide distribution in the northern hemisphere from Canada to Japan. Five Betula species, namely B. litwinowii Doluch., B. medwediewii Regel, B. pendula Roth., B. raddeana Trautv. and B. megrelica Sosn. are naturally growing in eastern and northern Georgia, at high altitudes. Only B. megrelica is endemic to Georgia [2]. The Birch tree has a long history of medicinal use in different countries and cultures to cure skin diseases especially eczema, infections, inflammations, rheumatism and urinary disorders. Diverse phytochemical investigations of Betula species have shown that they contain mainly phenolics, flavonoids, tannins, saponins, glycosides, sterols and terpene derivatives [3,6]. The therapeutic benefit of medicinal plants is often attributed to their antioxidant properties [5,7]. Phenolic glycosides are important secondary compounds in trees of the genus Betula as well as other plant species in the family Betulaceae. Flavonoids are one of the most important groups of bioactive compounds in plants, which exist in the free aglycones and the glycoside forms showing a diverse structure and a broad range of biological activities. Flavonoids include several classes of compounds with similar structure having a C6-C3-C6 flavone skeleton. They are differentiated on the degree of unsaturation and oxidation of the three carbon segment. Within different subclasses further differentiation is based on the number and nature of substituent groups attached on the rings. Mostly they occur in O-glycosidic forms with a number of sugars such as glucose, galactose, rhamnose, arabinose, xylose and rutinose but they are also present as C-glycosides. Flavonoid glycosides have many isomers with the same molecular weight but different aglycone and sugar component at different positions attaching on the aglycone ring [1,4]. Materials and methods. The leaves of Betula medwediewii Regel were collected in Georgia in april 2010 and identified by Dr. Tsiala Gviniashvili, a botanist from the Institute of Botany. Voucher specimens N 9708 were deposited in the Herbarium at the Department of Pharmacognosy and Botany, Faculty of Pharmacy, Tbilisi State Medical University. Sample Preparation for LC/MS/MS and HPLC Analysis. The leaves of B. medwediewii Regel were dried and ground into powder. Two grams of powdered leaves were mixed with 100 ml methanol, and then placed on a rotating shaker at 200 rpm for 6 h. Finally, the filtrate was collected, and filtered through a 0.45 _µm nylon filter. A 10 µl volume extract was injected into the HPLC column for analysis by LC-DAD/MS/MS. Standards and solvents. Apigenin, luteolin, kaempferol, myricetin, quercetin, naringenin, rutin, hyperoside, elagic-, ferulic-, galic acid-, vanillic- and p-coumaric acid were purchased from Sigma. Methanol, acetonitrile and formic acid were of HPLC grade (Sigma, Merck). LC-DAD/ESI-MS/MS analysis. Quantification of phenolics was performed by using an AGILENT 190

191 TECHNOLOGIES 1290 Infinity LC system consisting of a solvent degasser, a quaternary pump, an auto sampler, a thermostatic column compartment and a DAD and coupled to a AGILENT TECHNOLOGIES 6460 Triple quadrupole LC/MS.The column was a 200 mm X 4 mm i.d., 3 μm particle size Zorbax Eclipse C18, maintained at 35 0 C and protected with a UHPLC GUARD Zorbax Eclipse column of the same material using 0.5% aqueous formic acid (solvent A) and 0.5% formic acid in 50/50 v/v acetonitrile-methanol (solvent B). A stepwise gradient from 10% to 90% solvent B was applied at a flow rate of 0.5 ml/min for 46 min. The HPLC profiles were monitored at 210, 254, 325 and 340 nm, and the UV/Vis spectra were recorded from 190 to 650 nm. The volume injected was 10 µl. Electrospray mass spectra data were recorded on a negative ionisation mode for a mass range m/z 100 to m/z 1000.The interface was set at the following values: curtain gas 10; ion spray voltage 4.0 kv, source temperature C, nebulizing gas 40 psig; heating gas 10 psig; The acquisition method consisted of an information-dependent acquisition. Precursors were selected by using an enhanced full scan as the survey scan. The three most intense ions were analyzed using an enhanced resolution experiment. The concentration of each substance was measured by comparing it with calibrations made with the pure compound analyzed under the same conditions and linear regression coefficients between and were obtained. The samples were analyzed in duplicate. Results and discussion. Purification of the methanol extract from B. medwediewii Regel by repeated column chromatography yielded fractions rich in phenolic compounds, which were studied by LC/MS/MS. The optimum conditions were applied to the identification of the compounds. The purpose of this research was to identify phenolic compounds, quantify main flavonoids and phenolic acids and to isolate a flavonoid glycoside that was found to be characteristic for B. medwediewii Regel A sensitive, accurate and specific method coupling high performance liquid chromatography (HPLC) with diode array detector (DAD) and electrospray ionization mass spectrometry (MS) was developed for the separation and identification of phenolic acids, flavonoid glycosides and aglycones in the methanolic extract of B. litwinowii Doluch. The molecular masses of phenolic acids and flavonoids were assigned by electrospray ionization mass spectrometry. The subsequent structure characterization was carried out by a tandem mass spectrometric method. Fragmentation behavior of flavonoid glycosides and phenolic acids was investigated using mass spectrometry in negative mode. The MS, MS/MS and UV data together with HPLC retention time (TR) of phenolic acids and flavonoids allowed structural characterization of these compounds. After LC-DAD and MRM analysis Apigenin, rutine, luteolin, kaempferol, myricetin, naringenin, hyperozide, quercetin, p-coumaric-, ellagic-, ferulic-, gallic-, vanillic acides were determined in B. medwediewii Regel (Table). Fragmentation of aglycones provided characteristic ions for each family of flavonoids. In the spectra of the flavanoid glycosides present both ions the deprotonated molecule [M-H] - of the glycosides and the ion corresponding to the deprotonated aglycone [A-H] -. Hyperoside was identified on the bases of the product ion spectrum and comparison with literature data. The HPLC-DAD chromatograms and total ion chromatograms (TIC) in negative mode of the extracts of B. medwediewii Regel are shown in Figure. mau 120 DAD1 A, Sig=254,100 Ref=360,100 (BACKUP\ \VAKH2\ D) MSD1 TIC, MS File (BACKUP\ \VAKH2\ D) APCI, Pos, Scan, Frag: 70 min Fig. HPLC-DAD chromatogram of methanolic extract of B. medwediewii Regel λ=254 nm; TIC chromatogram of methanolic extract of B. medwediewii from HPLC-(-) ESI-MS 191 min

192 Table. LC-MS-MS characteristics of flavonoids and phenolic acids Flavonoids MS m/z [M-H]- MS/MS ions, m/z (rel. Int. %) CV/CE Cone Voltage / Collision Energy Content (mg/g, dw) Apigenin (100), 117 (80) -35/-15 12,4 Rutine (100), 301 (40) -40/-30 9,3 Luteolin (100), 151 (85), 133 (50) -40/-30 5,9 Kaempferol (100), 285 (40) -60/-55 7,9 Myricetin (50), 151 (100), 137 (70) -40/-25 6,8 Naringenin (80), 151 (100), 271 (20) -40/-30 3,3 Hyperozide (5), 301(100) -40/-38 9,3 Quercetin (100), 121 (40), 301(20) -35/-25 10,7 Phenolics p-coumaric (100), 163 (40) -30/-15 17,1 Ellagic (100), 129 (70), 301(35) -40/-30 14,1 Ferulic (100), 149 (30), 178 (55) -30/-20 9,3 Gallic (10), 125 (100) -25/-15 18,4 Vanillic (100), 123 (30) -40/-20 5,7 Conclusion An HPLC ESI-MS/MS based method described in this paper was proven suitable and sensitive to determine different flavonoids in B. medwediewii Regel extract. The existence of polyphenols are observed in B. medwediewii Regel for the first time. In addition, we have proposed an HPLC UV based method for the determination of several flavonoids, which can offer quite good linearity, accuracy, precision and low limit of detection. All results demonstrate this method is suitable for the quality control of B. medwediewii Regel leaves and its products. REFERENCES 1. De Rijke E., Out P., Niessen W.M.A., Ariese F., Gooijer C., Brinkman U.A. Th. Analytical separation and detection methods for flavonoids. J. Chromatogr. A 2006; 1112: Gagnidze R. Vascular Plants of Georgia a Nomenclatural Checklist. Tbilisi, Republic of Georgia: 2005; Gattuso G., Barreca D., Garguilli C., Leuzzi U., Coristi C., Flavonoid composition of citrus juice. Molecules 2007;12: Naczk M., Shahidi F. Extraction and analysis of phenolics in food. J. Chromatogr. A 2004; 1054: Scalbert A, Manach C, Morand C. et al. Dietary polyphenols and the prevention of Diseases. Crit Rev Food Sci Nutr. 2005; 45(4): Vedernikov D., Galashkina N., Roshchin V. Esters of Betula pendula (Betulaceae) buds. Rastitel'nye Resursy 2007; 43(3): Zardiashvili L. Jokhadze M., Kuchukhidze J. Mshvildadze V.Antioxidant polyphenols from Betula raddeana growing in Georgia. Tbilis State Medical University Collection of Scientific Works XLIV. Tb.: 2010; SUMMARY DETERMINATION OF POLYPHENOLS IN BETULA MEDWEDIEWII GROWING IN GEORGIA USING HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY WITH DIODE ARRAY DETECTION AND ELECTROSPRAY IONIZATION MASS SPECTROMETRY Zardiashvili L., Jokhadze M., Kuchukhidze J., Chincharadze D., Berashvili D., Bozhadze A. Tbilisi State Medical University, Department of Pharmacognosy and Botany, Georgia 192

193 Phenolic compounds, including phenolic acids and flavonoids are considered to be the major bioactive compounds in Betula medwediewii Regel A sensitive method coupling high-performance liquid chromatography with diodearray detector and electrospray ionization mass spectrometry was optimized for the separation and identification of phenolic acids, flavonoid glycosides and flavonoid aglycones in the extract of B. medwediewii Regel Fragmentation behavior of flavonoid glycosides and phenolic acids were investigated using ion mass spectrometry in negative electrospray ionization. The MS, MS/MS and UV data of phenolic acids and flavonoids allowed structural characterization of these compounds. An accurate, precise and sensitive LC-DAD method for quantification of five phenolic acids (elagic-, ferulic-, galic acid-, vanilic- and p-coumaric acid), two flavonoid glycosides (rutin and hyperoside) and six flavonoid aglycones (luteolin, apigenin, kaempferol, naringenin, myricetin, quercetin) in B. medwediewii Regel extract was validated for the first time in terms of linearity, limit of detection, limit of quantification, precision and accuracy. reziume saqartvelosi gavrcelebuli Betula medwedewii-s polifenolebis gansazrvra maralefeqturi sitxuri qomatografze dioduri da masspeqtrometruli deteqtorebis gamoyenebit zardiasvili l., joxaze m., kuwuxize j., WinWaraZe d., berasvili d., bojaze a. Tbilisis saxelmwifo samedicino universiteti, farmakognoziis da botanikis departamenti, saqartvelo fenoluri SenaerTebi, kerzod fenolmjavebi da flavonoidebi warmoadgenen saqartvelosi gavrcelebuli mcenaris _ aryis (Betula medwedewii oj. Betulaceae) ZiriTad biologiurad aqtiur nivtierebebs. avtorebis mier SemuSavebulia mgrznobiare maralefeqturi sitxur qromatografiuli metodi ultraiisferi dioduri da eleqtronebis gafrqveviti ionizaciis deteqtorebit rac uzrunvelyofs fenolmjavebis, flavonoiduri glikozidebis da aglikonebis srulad dayofas da identifikacias. MS, MS/MS da ui speqtrebis safuzvelze Seswavlialia polifenolebis struqturuli maxasiateblebi. SemuSavebulia B. medwediewii Regel fotlebsi xuti fenolmjavis (elagis, ferulis, galis, vanilis, p-kumaris), ori flavonoduri glikozidis (rutini, hiperozidi) da eqvsi flavonoiduri aglikonis (luteolini, apigenini, kempferoli, naringenini, miricetini, qvercetini) raodenobrivi gansazrvris metodi. metodis validireba Catarda iseti kriteriumebit rogoricaa sworxazovneba, gansazrvris minimumi, armosaceni minimumi da sizuste. azitromicinis Semcveli preparatebis in vitro bioeqvivalentobis Seswavla CikvilaZe T., baramize q., jorjikia m., koberize n., namgalaze S. Tbilisis saxelmwifo samedicino universitetis farmacevtuli da toqsikologiuri qimiis departamenti; `globaltesti~-s sagamocdo laboratoria, saqartvelo drevandeli mdgomareobit, qlamidiis sawinaarmdego, dadasturebuli moqmedebis mqone medikamentebis raodenoba atamde originaluri preparatia, romlebic warmoadgenen antibiotikebis 3 jgufs makrolidebi, tetraciklinebi da ftorqinolonebi. Tumca, mxolod or matgans, azitromicinsa da doqsiciklins azleven rekomendacias rogorc 193

194 evropis, aseve amerikis Sesabamisi maregulirebeli organoebi [1-3]; magram azitromicinisa da doqsiciklinis `wyvilidanac~ upiratesobas aniweben azitromicins. azitromicini qimiurad (2R,3S,4R,5R,8R, 10R,11R,12S,13S,14R)-13-[(2,6-dideoqsi-C-meTil-3-OmeTil α-l-ribo-heqsopiranozil)oqsi]-2-etil -3,4,10-trihidroqsi -3,5,6,8,10,12,14-heptameTil - 11-[[3,4,6- trideoqsi -3- (dimetilamino)-β-d-qsilo-heqsopiranozil]oqsi]-1- oqsa-6- azaciklopentadekan-15-on-ia, misi qimiuri formulaa C 38 H 72 N 2 O 12 2H 2 O. azitromicini azalidebis qveklasis pirveli warmomadgenelia da klasikuri makrolidebisagan struqturit gansxvavdeba. kerzod, mas aqvs 15 wevriani makrocikluri birtvi, magram birtvsi metilirebuli azotis arseboba gansakutrebul Tvisebebs aniwebs, rogoricaa mjavamdgradoba, antimikrobuli aqtivobis speqtris gafartoeba, unari, SeaRwios ujredis kedelsi [4,5]. nax. 1. azitromicinis qimiuri struqtura azitromicini SigniT mirebisas swrafad Seiwoveba, nawildeba mtels organizmsa da qsovilebsi, arwevs maral koncentracias, rac ganpirobebulia misi marali lipofilobit. SratSi maqsimaluri koncentracia arinisneba 2,5 2,96 saatis Semdeg; bioserwevadoba Seadgens 37%, naxevargamoyofis periodi saati; eliminirdeba ZiriTadad ucvleli saxit, narvelit, mcire nawili TirkmelebiT. azitromicini xasiatdeba marali antimikrobuli (antiqlamidiozuri) aqtivobit, unarit, SeaRwios da dagrovdes ujredsi, damatebit miarwios antebis kerasi. unda arinisnos, rom yvela CamoTvlili Tviseba dadgenilia mxolod originaluri preparatisatvis, anu im preparatisatvis, romelic pirvelad iqna sintezirebuli da romelmac gaiara eqsperimentuli da klinikuri kvlevebis yvela cikli. aset preparats warmoadgens sumamedi (pliva, xorvatia). originaluri preparati yoveltvis ertia, jenerikebi ki bevri. kvlevebi acvenebs, rom jenerikebis xarisxi sxvadasxvaa da mati standartis xarisxic xsirad ar Seesabameba originaluri preparatisadmi wayenebul motxovnebs. cnobilia, rom jenerikisadmi wayenebuli ZiriTadi motxovnaa originalisadmi upirobo bioeqvivalenturoba [6]. winamdebare nasromis mizani - saqartvelos farmacevtul bazarze arsebuli azitromicinis Semcveli preparatebis in vitro bioeqvivalentobis Seswavla. kvlevis masala da metodebi. kvleva ganxorcielda rogorc brma, SedarebiTi randomizebuli, jvaredini kvleva ori periodit da ori TanmimdevrobiT da Sesrulda janmo-s da FDA-s rekomendaciebis Sesabamisad, TiToeuli mwarmoeblis nawarm 12 tabletze. 194

195 sakvlev obieqtebs, konfidencialobis dacvis miznit mieniwa kodebi 2, 3, 4 da 5. referentul preparatad gamoyenebul iqna Osumamedi (pliva, xorvatia), kodit 1. referentuli preparatis arcevani ganpirobebuli iyo imit, rom arnisnuli samkurnalo sasualebis xarisxi, usafrtxoeba da efeqturoba Seswavlilia wina da postmarketinguli kvlevebis dros. kvlevas vawarmoebdit xelsawyoze ERWEKA DT-600, romlis teqnikuri da saeqsploatacio maxasiateblebi mtlianad Seesabameba ass, britanetis da evropis farmakopeebis motxovnebs. gamotavisuflebuli sakvlevi nivtierebis raodenobas vsazrvravdit marali wnevis Txevad qromatografze - СТАЙЕР (Аквилон), sveti - luna 5u C18(2) x4,6mm, romlis teqnikuri da saeqsploatacio maxasiateblebi mtlianad Seesabameba ass, britanetis da evropis farmakopeebis motxovnebs da damowmebulia ssip `standartebis, teqnikuri reglamentebisa da metrologiis erovnuli saagento~-s mier. xsnadobis mirebuli profilebis referentul preparattan Sedarebis Sefasebas vaxdendit msgavsebis koeficientis mesveobit, romlis gansazrvris metodika ariarebulia janmo-s, FDA-sa da evrosaagentos mier: f 2 = 50 log {[1+ (l/n) t=1 n (R t T t ) 2 ] --0,5 100} monacemebis ganzogadebis miznit, vitvlidit gansxvavebis koeficientsac: n t= 1 1 = 100 n f Sedegebis statistikuri damusaveba movaxdinet programa Statistic for Windows 6.0 is mesveobit. gamovtvalet sasualo aritmetikuli mnisvnelobebi, standartuli gadaxra (SD) da variaciis koeficienti (CV); gamoviyenet agretve dispersiul analizsa da stiudentis t-testebze bazirebuli statistikuri metodebi. sarwmunod mivicnevdit P<0,05 mnisvnelobis mqone gansxvavebebs. janmo-s kriteriumebtan Sesabamisobis gansazrvris dros gamoviyenet 95%-iani sarwmuno intervalis qveda da zeda zrvrebi. eqvivalentobis kriteriumebi: referentul preparattan msgavsebis koeficienti ara umcires 50%, gansxvavebis koeficienti ara umetes 15%; SefuTvaze mititebuli, aqtiuri substanciis `azitromicini~-s - raodenobis ara umcires 80%-is gamotavisufleba 30 wutis ganmavlobasi kvlevis yvela obieqti Seesabameboda mwarmoebelta moqmed normatiul dokumentebs da farmakopeis statiebs [6]. eqsperimentuli nawili. `gaxsna~-s testis unificirebuli metodikis SesarCevad ganxorcielda am testis mimart moqmedi normatiuli dokumentebis motxovnebis donis SedarebiTi Sefaseba da mizansewonilad CaiTvala kvlevis Catareba USP 35 NF 30-s farmakopeis statiasi arwerili metodikit are 900 ml fosfaturi buferi (ph=6,0), gaxsnis dro 30 wt, nicabis brunvis sicqare 75 br/wt, ares temperatura 37±1 0 C drois intervalebi ki arebuli iqna amerikis sakvebi produqtebisa da samkurnalo sasualebebis saagentos (FDA) motxovnebidan, kerzod, 5, 10, 15 da 30 wt [7]. sakvlevi xsnari: fiqsirebul drois monakvetsi xsnadobis aredan arebul 10 ml-s vfiltravdit, filtratis 4 ml vatavsebdit 25 ml-ian gamzom kolbsi, moculobas Wdemde vavsebdit mozravi fazit da kargad vurevdit. 195 R( t) T ( t) t= 1 R( t)

196 standartuli xsnari: 29,0 mg (zusti wonaki) azitromicinis standartul nimuss vatavsebdit 100ml-ian gamzom kolbsi, vxsnidit 50 ml `gamxsnel aresi~, moculobas imave gamxsnelit vavsebdit Wdemde da kargad vurevdit. mirebuli xsnaris 4 ml vatavsebdit 25 ml-ian gamzom kolbsi, moculobas Wdemde vavsebdit mozravi fazit da kargad vurevdit. raodenobrivi gansazrvra marali wnevis Txevadi qromatografuli metodit: sveti - C 18, λ -210 nm, nakadis sicqare 1,5 ml/wt, svetis temperatura 50 0 C, mozravi faza: acetonitrili-metanoli xsnari `a~ (9:3:8); xsnari `a~-s 1 ml Seicavda 4,4 mg orfuzian natriumis fosfats da 0,5 mg oqtansulfonat natriums; ph fosformjavit migvyavda 8,20±0,05-mde. ganvsazrvret agretve azitromicinis standartuli nimusis xsnaris stabiluroba ph=6,0-ze. dadginda, rom azitromicinis standartuli nimusis xsnari stabiluria 2 saatis ganmavlobasi otaxis temperaturaze Senaxvisas. K cxrili 1. azitromicinis gamotavisuflebuli raodenoba 30 wutis Semdeg azitromicinis sakvlevi nimusis kodi gamotavisuflebuli raodenoba 30 wutis Semdeg, % 97,9 81,3 80,1 82,6 80,3 kriteriumi % > 80% 150 azitromicinis გამოთავისუფლებ ული რაოდენობა, % dro 20 (wt) nax. #2. referentuli (1) da sakvlevi (2,3,4,5) preparatebis xsnadobis profilebis Sedareba ph 6,0-ze cxrili 2. sakvlevi preparatebis referentultan Sesabamisobis ( f 2 ) da gansxvavebis ( f 1 ) koeficientebi (n=12) sakvlevi medikamentis kodi Sesabamisobis koeficienti Ggansxvavebis koeficienti 2 43,45 17, ,19 24, ,55 15, ,85 25,76 kriteriumi % > 50% < 15% kvlevis Sedegebis ganxilva. Seswavlilia, saqartvelosi registrirebuli, azitromicinis Semcveli otxi myari oraluri wamlis formidan moqmedi nivtierebis in vitro gamotavisufleba. 196

197 dadgenilia, rom yvela obieqti akmayofilebs farmakopeis statiis (USP) motxovnas testze `gaxsna~, imdenad, ramdenadac yvela nimusidan xdeba 80%-ze meti raodenobit azitromicinis gamotavisufleba 30 wutis ganmavlobasi; Sedarebulia sakvlevi nimusebis da referentuli preparatis xsnadobis profilebi; dadgenilia, rom arc erti nimusis xsnadobis profili ar Seesabameba referentuls da Sesabamisad, es nimusebi ar aris referentuli medikamentis eqvivalenturi. amdenad, in vitro kvlevis Sedegebi aradamakmayofilebelia da Terapiuli eqvivalentobis dasadgenad moitxovs damatebit in vivo kvlevas. literatura 1. Европейское руководство по ЗППП. Int J STD/AIDS. 2001; 12(Suppl 3). 2. Руководство по лечению ЗППП Центры по контролю и предупреждению заболеваний (СДС, Атланта, США). САНАМ: 2003; Методические материалы по диагностике и лечению наиболее распространенных ИППП и заболеваний кожи. М.: Геотар-Мед; 2003: Ballow CH, Amsden GW. Azitromycin: the first azahde antibiotic. Ann Pharmacother. 1992; 26: Olsen KM, San Pedro G, Gann LP et al. Intrapulmonary pharmacokinetics of azitromycin in healthy volunteers given five oral doses. Antimicrob Agents Chemother. 1996; 40: WHO Technical Report Series. No. 937; 2006: app. N reziume azitromicinis Semcveli preparatebis in vitro bioeqvivalentobis Seswavla CikvilaZe T., baramize q., jorjikia m., koberize n., namgalaze S. saxelmwifo samedicino universitetis farmacevtuli da toqsikologiuri qimiis departamenti; `globaltesti~-s sagamocdo laboratoria, saqartvelo Seswavlilia, saqartvelosi registrirebuli, azitromicinis Semcveli otxi myari oraluri wamlis formidan moqmedi nivtierebis in vitro gamotavisufleba. dadgenilia, rom yvela obieqti akmayofilebs farmakopeis statiis motxovnas testze `gaxsna~, imdenad, ramdenadac yvela nimusidan xdeba 80%-ze meti raodenobit azitromicinis gamotavisufleba 30 wutis ganmavlobasi. Sedarebulia sakvlevi nimusebis da referentuli preparatis xsnadobis profilebi; dadgenilia, rom arc erti nimusis xsnadobis profili ar Seesabameba referentuls da Sesabamisad, es nimusebi ar aris referentuli medikamentis eqvivalenturi. amdenad, in vitro kvlevis Sedegebi aradamakmayofilebelia da Terapiuli eqvivalentobis dasadgenad moitxovs damatebit in vivo kvlevas. SUMMARY STUDY OF IN VITRO BIOEQUIVALENCE OF THE MEDICINES CONTAINING AZITROMYCIN Chikviladze T., Baramidze K., Jorjikia M., Koberidze N., Namgaladze Sh. Tbilisi State Medical University, Department of Pharmaceutical and Toxicological Chemistry; "Globaltest", LLC, Testing Laboratory, Georgia 197

198 Examined the release of 4-s solid dosage forms of medicines azitromycine from different manufacturers, registered in Georgia. It is established that all of the samples are compliant with monographs USP on test "dissolution". But when comparing profiles dissolve has proved that all samples are not equivalent position. The data in vitro studies are not satisfactory and thus require therapeutic equivalence (optional) in vivo studies. MODELS OF SOME PHYSICAL PROPERTIES OF ADAMANTINE-CONTAINING BIOACTIVE COMPOUNDS Lekishvili G., Arziani B. Tbilisi State Medical University, Department of Medical Chemistry, Georgia The technique of quantitative structure-activity relationship (QSAR) has been in use for designing reliable models of biological activities and physical-chemical properties of organic molecules. The aim is to assist organic and pharmaceutical chemists to plan and to carry out purposeful synthesis of compounds with the given spectrum of desirable characteristics. The aforementioned approach is based on representation of molecular structures with numeric quantities. They are calculated via straightforward algorithms and are known as molecular descriptors. Among the latter, considerable attention is granted to the autocorrelation based descriptors [1], GETEWAY [2], WHIM [3], Burden Eigenvalues, and traditional graph-theoretical invariants [4]; they were selected for our research. Our data set [5] contained 16 compounds. In order to detect outliers i.e., the compounds, which did not belong to the modeling population, we performed PCA [6]. However, unlike our previous contribution [7], we did not identify any of the investigating compounds as outliers. As one can see (Fig. 1), compounds #7, #8, #13, #14, #15 and #16 are placed somehow remotelyfrom the main group. This alone does not allow for their removal. For example, the Burden eigenvalues reveal that only compound #8 is an outlier(fig. 2). When we used the Randic type invariants, none of the compounds left the main group (Fig. 3). Fig. 1. The outlier detection by means of PCA. The descriptor used is GETEWAY 198

199 Therefore, we decided to keep all of the compounds in the training dataset.it is noteworthy that the Randic type invariants clearly output several clusters of compounds. Our final step was establishment of relationships between these descriptors and the physical properties measured experimentally. Our studies show that best model was achieved by employing, again, the GETAWAY descriptors. We used PLS[8]as the number of predictors was much higher than that of cases. We used cross-validation to define the optimal number of latent variables. In our study, we used 13 compounds in training set and 3 for the crossvalidation tests. Of course, the prediction power was lower in case of cross-validation. We modeled both melting points (mp) and retention factors (R f ) within the same model, which, therefore, had 2 responses. The results of modeling look impressive as the square of the average correlation coefficient was as high as The PRESS was also good enough (Table 1). One can examine theexperimental and calculated values (Table 2). A reader should take into account that compounds 4, 13, 16 produced the test (validation) set. Experimental: We used MDL Isis Draw 2.5.SP4 to build molecular models. Afterwards, we concatenated the models into the dataset by use of EdiSDF The textual format of the dataset was SDF. We used VCC-Lab e- Dragon web application for calculation of molecular descriptors.statistic 6.0 was a tool of our choice for building PCA and PLS models. Fig. 2. The outlier detection by meansof PCA. The descriptors used are theburden eigenvalues Fig. 3. The outlier detection by means of PCA.The descriptors used here are the Randic type invariants 199

200 Table 1. The statistical parameters of the model Latent Var. Increase R 2 on Y Average R 2 on Y Increase R 2 on X Average R 2 on X R 2 for mp R 2 for R f Sc. PRESS, mp Sc. PRESS, R f Average Sc.PRESS Table 2. Experimental vs. calculated R/s mp, calc R f, calc mp, R f, exp mp, calc R f, calc mp, exp R f, exp exp REFERENCES 1. Hemmer M C., Steinhauer V., Gasteiger J. Vibrat. Spectr., 1999; 19: Consonni V., Todeschini R., Pavan L. J. Chem. Inf. Comput. Sci. 2002; 42: Todeschini R., Lesagni M., Marengo E. J. Chemom. 1994; 8: Todeschini R., Consonni V. Handbook of Molecular descriptors. Wiley-VCH, Wein Heim 2001; Denisova L.I., Kosareva V.M., Lopukhova K.E., Solonenko I.G. Kh. F. Zh. 1975; 9: Otto M. Chemometrics. Wiley-VCH, Weinheim: 1999; Lekishvili G., Asatiani L., Zurabishvili D. Georgia Chemical Journal 2004; 4(3): Geladi P., Kowalski B.R. Anal. Chim. Acta 1986; 185: CASE STUDY AND PROBLEM BASED METHODOLOGY IN PUBLIC HEALTH Zarnadze Sh., Zarnadze I., Kitovani D., Lomtadze L., Kajrishvili M., Kuparadze M. Tbilisi State Medical University, Department of Public Health, Georgia Case Study and EBM (Evidence-Based Medicine) is a relatively new concept in Public Health, and medical education, but one that is rapidly gaining acceptance as an important approach in assisting medical students, residents, and practicing physicians with their clinical decision-making. Case Study and Problem Based Llearning in Medical education has become a widespread and effective method of using the medical literature. It has four basic steps: the development of a clinical question, the literature search for the appropriate medical literature to address the clinical question, critical appraisal of the acquired paper, and 200

201 application of the results of the research paper to the patient at hand. Goals - analysis of effectiveness of teaching methodology. Methods. Observational Study Results and discussion. The use of CS and PB (EBM) should allow for patient care that is the most effective possible, the most cost-effective, and the safest. The skills to be mastered to use the EBM approach include that of question formulation, literature searching, critical appraisal of articles, and application of evidence. The resources needed include the need for computers and Internet access to full articles, a printer, and functional use of the English language. Moreover, this is a lifelong endeavor, so practice and mentorship are useful. The CS and PB component in Tbilisi State Medical University has the aim of assisting students to learning objectives. Training in the CS AND PB learning method will be provided at the beginning of the Module. The Module Paper has the aim of assisting students to learning objectives. The Annotated Bibliography supports all learning objectives. Students are to select their own reading, in consultation with other students and faculty, amounting to at least 1,000 pages. Students are to maintain an annotated bibliography of their reading, and this must be delivered to the Module Director at the completion of the Module. Seminars, practical lesson, individual work, discussion Critical analyzes of article, project presentation. Characteristics of CS and PBL in Teaching curricula in TSMU : Problems form the organising focus and stimulus for learning, Problems are a vehicle for the development of problem-solving skills, New information is acquired through self- directed learning, Learning is student centred, Learning occurs in small student groups,teachers are facilitators or guides Problems form the organising focus and stimulus for learning. Process of PBL : Students confront a problem, In groups students organise prior knowledge and attempt to identify the nature of the problem, Students pose questions about what they do not understand, Students design a plan to solve the problem and identify the resources they need, Students begin to gather information as they work to solve the problem. Role of the tutor: facilitator, help clarify discussion, suggest avenues of investigation, put problem in context of other learning, suggest prioritising of learning issues, intervene in negative group dynamics, guide discussions about group process. WHY USE EBM- Medicine is a rapidly changing field,huge amount of literature/research Slow dissemination of new data. GOALS of EBM; Improve patient outcome, Improve patient safety, Improve cost-effectiveness DOMAINS of EBM: Diagnosis, Therapy, Prognosis, Harm / Etiology, Clinical Practice Guidelines, Systematic Reviews. How do we practice EBM? Clinical Question, Literature Search, Critical Appraisal Application of Results, Self-Evaluation & Improvement. KEY to EBM PRACTICE: Answerable,Searchable, Appraisal, Applicable SPECIFICS: Cases, Worksheets, Pre & Post tests, Inpatients, Outpatients, Journal Club, Group Sessions, Grand Rounds, Lectures Clinical Queries is a pre-set study design filter that is applied to a concept search entered by the searcher Caveats:Filters were validated for indexing applied but PubMed automatically searches 1966+; results not always dependable Filters are based on assumptions that do not always apply e.g. randomized controlled trials for Harm q s are not included in a Harm filtered search Keep concept search as simple as possible, using MeSH terms, for better success Write out your question PIO 201

202 Identify the key concepts from the question Consider/determine the standard medical terminology for each term and other related terms Group similar terms together (if necessary) using OR; search each concept independently; Gather all concepts together using AND; Evaluate and refine approach as necessary; Understand the various study designs appropriate for therapy trials; Understand the fundamental concepts in appraising a therapy tria;l Ability to appraise a therapy trial; Types of Therapy Studies: Phase I: Safety study: novel intervention; Phase II: Dose Finding: generally not randomized; Phase III: Large Clinical Trial (e.g. Randomized Controlled Trial): comparison to either placebo or standard of care. Meta-Analysis: A summary of individual studies (i.e. RCTs) with homogenous data that is pooled and upon which statistical analysis is performed. Applying limits is useful as it can narrow down large results into a manageable number fairly easily. The following can be applied as limits: Publication type: randomized controlled trial, practice guidelines, reviews, Publication date, Age, Human or animal studies, Language. Resources: Reviews or Clinical Practice Guidelines: PubMed, Cochrane Library, National Guideline Clearinghouse, various association websites. Evidence-Based Resources: Cochrane Library, Clinical Queries filter in PubMed, Clinical Evidence Journals: citation databases such as PubMed. Conclusion: Outcomes of CS and PBL are the Problem-solving skills, Self-directed learning skill, Ability to find and use appropriate resources,critical thinking,measurable knowledge base, Performance ability, Social and ethical skills, Self-sufficient and self-motivated, Leadership skills,ability to work on a team, Communication skills, Proactive thinking, Congruence with workplace skills. REFERENCES 1. Elmslie T., Goldman F., Spasoff B. An Introduction to Evidence-Based Medicine: SOCCS component. Renal Block: Hennekens Ch. Epidemiology in Medicine. Little, Brown, and Company: Oxman A., Sackett D. et al. Users Guides to the Medical Literautre. JAMA How to Get Started. JAMA 1993; 270(17). 4. Sackett D. et al. Clinical Epidemiology: A Basic Science for Clinical Medicine. Second Edition. Little, Brown, and Company: Sackett D., Richardson W.S., Rosenberg W., Haynes R.B. Evidence-Based Medicine: How to Practice & Teach EBM Churchill Livingston, Fagan TJ. Nomogram for Bayes s theorem (C). N Engl J Med. 1975:293: Hankey, G., Warlow, C. Symptomatic carotid ischaemic events: safest and most cost effective way of selecting patients for angiography, before carotid endarterectomy. BMJ 1990; 300: Oxman, A., Sackett, D., et al. Are the Results of the Study Valid? JAMA 1994; 271(5). 9. Oxman, A., Sackett, D., et al. What Are the Results and Will They Help Me in Caring For My Patients?JAMA 1994; 271(9). 10. Sackett D. et al. How to Read Clinical Journals:II. To learn about a diagnostic test. CMAJ 1981; 124: Sackett D. et al. Evidence-Based Medicine: How to Practice & Teach EBM. Churchill Livingstone: Sauve J., Laupacis A. et al. Does This Patient Have a Clinically Important Carotid Bruit? JAMA1993; 270(23):

203 SCREENING OF ANTIDERMATIC ANTHRAQUINONES Muzychkina R., Korulkin D. Faculty of Chemistry and Chemical Technology, al-farabi Kazakh National University, 71 Al-Farabi Avenue, Almaty, , Kazakhstan Creation of high-performance low-toxicity medicine preparations is one of the most important challenges for medicine, pharmacology and organic chemistry. Scientists of many countries screening the biologically active compounds extracted from natural materials, or synthesized, or synthesized as a result of structure change in wellknown biologically active compounds by inclusion of new functional groups, replacement of heteroatoms, creation of new types of chemical bonds and other processes. Among high-performance low-toxicity medicine preparations, especially, preparations received after selective action, an important place is occupied by the derivatives of anthraquinone. The bibliographic data well proven the biological activity of anthracene-containing plants, natural anthraquinones, their synthetic analogues and phytopreparations. Here should be noted that synthetic analogues have wider spectrum of biological activity. Ramon is the new anthraquinone-containing preparation, received from a plant; it destines for external use to treat psoriasis, eczema and other skin diseases. The Ramon has anti-inflammatory, anti-itch, resorptional, emollient and reductional effect. The Ramon is non-toxic preparation, which is easily absorbed by skin and patients stand it well; clinical observations during 7 years have not revealed contraindications during the treatment of grown-ups and children. This preparation does not have allergenic reactions; LD 50 after intraperitoneal injections to mice is 230 mg/kg. It is possible to regenerate the Ramon on the expiration date or when it has been kept in a wrong way. This fact allows saving raw plant material for receiving this preparation. Anti-itch effect is observed after 1-3 times of application for lesion sites. On the 2-4 day, hyperemia decreases, infiltration resorbs and the considerable reduction or full stop of itch is observed; lesion seats are cleared up of psoriatic patches. It could treat herpes; especially effective application of the product at the beginning of the process. In contrast to Synalar (Fluocinolone acetonide), Flutsinar, Larinden C, H, Flumethasone pivate, Ultralan, Oxycort, Nystatin, Kanesten, Klotrimasol it is not an inhibitor for hemopoietic and fermental systems of a human. It is supposed, that mechanism of the Ramon s effect is the following: participation in reduction-oxidation processes of the organism and affect on skin membranes and on subcellular layer. During clinical researches the patients were divided according to the state of the illness: in psoriasis group were the patients from 9 to 28 years, in eczema group - the patients from 3 months to 10 years, the rest from 1 to 17 years. Patient s ages were from 5 up to 57 years. Course of treatment was 1-3 weeks; in the case of recurrence the course was repeated. Concentration of ointments and solutions was from 1 to 10%. The maximal effect was noted when there was application of ointment after removal of patches with the help of thermoprocedures or mechanically. Each 10 days blood tests and urinalysis were taken. Aldolase s and transketolase s activity was checked in blood and on skin. Along with this antitoxic function of liver, carbohydrate (sugar in blood) and protein metabolism (common protein, fractions of protein) were studied. Researches made in dynamic have not revealed departure from the first quantities. All the patients have been discharged from hospital with considerable improvement or full clinic recovery. Ramon preparation was tested on 1248 patients in 11 clinics in Russia, Belarus, Uzbekistan and Kazakhstan in three dosage forms with active substance concentration ranging from 1 to 10%. The results are shown in Table

204 Table1. The results of the clinic tests Diagnosis Psoriasis progressive stage stationary Eczema professional Numb. of pat-s Full disappear. of clin. sings 67% Conside rable improv. 29% Partial improv 2% Absence of effect 2% Side-effect No Light erythema 0.8% 0.5% it increase - - micotic seborrheic Herpes no Lichen ruber planus no Neurodermite eczematous % Deverzhi lichen no Ichthyosis no Darier s dyskeratosis 6 10(1) no Hyperkeratosis of palms & soles of legs no Prurigo no As a result of clinical approbation 2% ointment on the lanoline base was chosen. The main results: complete disappearance of clinical symptoms or significant amelioration for psoriasis were observed in 96% of patients, professional eczema improvement was observed in 97% of cases, mycotic eczema in 89% of cases, seborrhea in 98% of cases, herpes in 96% of cases, lichen rubber planus - in 86% of cases, eczema-like neurodermatitis in 80% of cases, vitiligo in 78% of cases. In the clinic test reports it was pointed out that the main advantage of the preparation in comparison with traditional medicines is reduction of lesion sites infiltration in a shorter period of time (5-10 days), regression of psoriatic disseminated and reduced forms appearance. A disadvantage of the preparation was washing-resistant dyeing of linen. On pastures the preparation was tested on young cattle and was discovered of its efficiency in damaged eye cornea and animal s udder (as anti-inflammatory and wound-healing preparation). According to the data of the Institute of Ophthalmology, 2%, 1% and 0.5% ointments were studied on chinchilla rabbits, on which were modeled mild burns of cornea induced by acid and alkaline. 5% ointment was studied on the group of real patients. No visible symptoms of irritation of mucous membrane were registered. Morphological and cytological investigations confirmed positive influence of the preparation on reparative regeneration of the cornea, acceleration of the period of cornea epithalization, increase of visual acuity by unit. qartuliffarmacevtuli ganatlebis zogierti sakitxi abulaze n., alavize n. j. akaki weretlis saxelmwifo universiteti, qutaisi, saqartvelo bolo wlebsi mimdinare procesebma farmacevtuli kadrebis momzadebazec moaxdina zegavlena. Ffarmaciis itoriis Sesaxeb literaturuli monacemebis Seswavlam gamoavlina, rom saqartvelo arasdros CamorCeboda msoflio civilizacias. 204

205 Cveni kvlevis mizania, garkveva saidan iwyeba Tanamedrove farmacevtuli ganatlebis istoria, ra cvlilebebi ganicada man 1850-iani wlebidan dremde da Sesabamisi daskvnebis gamotana. pirveli aftiaqebis gacenistanave farmacia da provizoris profesia gansakutrebuli prestijulobit gamoirceoda mtels saqartvelosi. istoriisa da kerzod farmaciis istoriis kvlevis deduqciuri da sayoveltaod mirebuli sxva metodebis gamoyenebit arvnisnavt, rom XIX saukunis meore naxevarsi sawarmoo Zalebis dacqarebulma ganvitarebam dadebiti zegavlena moaxdina saqartvelosi farmaciis ganvitarebazec, rac gamovlinda aftiaqebisa da farmacevtuli personalis ricxvis zrdit. Aam periodsi Caeyara safuzveli Tanamedrove aftiaqis winapars viqtorianul aftiaqs. Aadgilze kadrebis momzadebis ararsebobis gamo, saqartvelos aftiaqebsi musaobdnen jer rusi, poloneli, ukraineli, latvieli, mogvianebit ki, qartveli specialistebi, romeltac profesiuli ganatleba moskovis, kievis, novorosiis (odesis), xarkovis, tartus, varsavisa da sxva universitetebsi hqondat mirebuli. XX saukunis 20-ian wlebamde saqartvelosi ar arsebobda farmacevtuli kadrebis mosamzadebeli specialuri umarlesi da sasualo-specialuri saswavleblebi. XIX saukunis meore naxevarsi rusetis mtels imperiasi, romlis Semadgenel nawils saqartveloc warmoadgenda, farmacevtul swavlebas hqonda Semdegi etapebi: - aftiaqaris Segirdoba; - aftiaqaris TanaSemwis wodebis mopoveba Segirdad musaobis 3-5 wlis stajit da sauniversiteto gamocdebis CabarebiT; - provizoris wodebis mopoveba aftiaqaris TanaSemwed 2-3 weli musaobis Semdeg da universitetsi Sesabamisi gamocdebis CabarebiT; - da bolos, sajaro disertaciis dacvit farmaciis magistris xarisxis mopoveba. A adgilze, saqartvelosi, SesaZlebeli iyo mxolod aftiaqaris Segirdebis momzadeba. Segirdisa da sasualo farmacevtuli kadrebis done ki mtlianad aftiaqis mepatronis profesiul momzadebaze iyo damokidebuli. mxolod Tbilisis saxelmwifo universitetis gaxsnit (1918 w.), Caeyara safuzveli farmacevtuli kadrebis momzadebis yvela etaps. aq samkurnalo fakultetze 1919 wlis oqtombersi gaixsna farmacevtuli ganyofileba da mastan farmaciisa da farmakognoziis katedra wels xelmzrvanelobam odesidan gamoiwvia profesori iovel grigolis Ze qutatelaze, romelic satavesi Caudga am katedras. i. g. qutatelazis usualo xelmzrvanelobit Camoyalibda farmacevtuli ganyofileba otxwliani saswavlo kursit wels gaixsna Tbilisis farmacevtuli teqnikumi. arnisnuli saswavleblebi gaxdnen umarlesi da sasualo-profesiuli ganatlebis kerebi saqartvelosi wels Tbilisis samedicino instituttan gaixsna farmacevtuli fakulteti. Aam periodidan momdevno naxevari saukunis manzilze (meoce saukunis ian wlebamde) umarlesi da sasualo farmacevtuli kadrebis momzadebis upiratesoba imasia, rom Seqmnili iyo rogorc sadiplomo, aseve diplomissemdgomi ganatlebis ertiani saxelmwifoebrivi sistema [1-3]. farmacevtuli ganatleba gasuli saukunis 50-iani wlebidan moicavda qvemot CamoTvlil etapebs (cxrili 1). sawiro gaxda cvlilebebis Setana farmacevtta saswavlo gegmebsi mesame, mimdinare etapis motxovnata gatvaliswinebit [4,5]. 205

206 cxrili 1. farmacevtuli ganatlebis etapebi Ffarmacevtuli praqtika Ffarmacevtuli ganatleba Ppirveli etapi wamlis damzadeba da ganawileba Ffizikur-qimiuri disciplinebi, 1980ww. farmacevtuli samsaxuris organizacia da srulyofa sawarmoo aftiaqebis ricxvis Semcireba, saaftiaqo samsaxuris specializacia (nomenklaturis mixedvit), mza wamlis formebis procentuli zrda, pacientis konsultacia ww. samkurnalo sasualebebit momaragebis decentralizebuli sistema, wamlis warmoebis Tanamedrove marali teqnologiebi, sainformacio samsaxuri, wamlis racionaluri gamoyeneba wlidan dremde. Mmeore etapi Mmesame etapi samedicino-biologiuri disciplinebis (patologia, farmakoterapia, biologia, klinikuri farmakologia) gazlierebuli swavleba farmaciis martva da ekonomika (marketingi), informatika, farmacevtuli teqnologia bioteqnologiit, farmakoepidemiologia, farmakoekonomika, standartizacia, metrologia, sertifikacia da wamlis xarisxis kontroli 1999 wlis 19 ivniss evropis 29 qveynis ganatlebisa da mecnierebis ministrebma msoflios uzveles sauniversiteto qalaq boloniasi xeli moaweres deklaracias (boloniis deklaracia), ritac safuzveli Caeyara ertiani evropuli saganmanatleblo sivrcis Seqmnis process, romelic miznad isaxavs erovnuli saganmanatleblo sistemebis dakavsirebas da unifikacias. mogvianebit 2010 wels luvenis komunikes mixedvit, ertiani saganmanatleblo sivrcis CamoyalibebasTan ertad warmocinda Semdegi prioritetebi: socialuri ganzomileba, studentze orientirebuli swavleba, ganatleba-kvleva-inovacia, swavla mteli sicocxlis ganmavlobasi, dasaqmeba, dafinanseba, yovelmxriv gamwvirvale meqanizmebi da a.s. dreisatvis boloniis processi, romelsac saqartvelo 2005 wels bergenis samitze SeuerTda, 49 qveyanaa CarTuli. swored bolo atwleulebis ganmavlobasi mimdinare procesebma gamoiwvia Zireuli cvlilebebi ganatlebis sistemasi zogadad, da farmacevtul ganatlebasi, kerzod. am etapze saqartvelosi moqmedebs 21 akreditebuli umarlesi farmacevtuli saganmanatleblo programa, mat Soris 14 sabakalavro, 7 samagistro da ateulobit profesiuli programa. Sesabamisad, saqartvelosi yovelwliurad kolosalurad izrdeba farmacevtuli `kadrebis~ raodenoba, Tumca saxelmwifos mxridan mati kvalifikaciis dadasturebis meqanizmi ar arsebobs. programebis akreditaciis procesi xorcieldeba akreditaciis zogadi principebis gatvaliswinebit ssip ganatlebis xarisxis ganvitarebis erovnuli centris mesveobit, magram samwuxarod, dreisatvis saqartvelosi ar arsebobs raime standarti, romelic gansazrvravda ra savaldebulo kursebs unda moicavdes an ra aucilebel kompetenciebze unda gadiodes farmaciis saganmanatleblo programebi, Sesabamisad programebi metad mravalferovania da satuoa Sesabamisi materialur-teqnikuri bazis arseboba qvemot CamoTvlili yvela saganmanatleblo dawesebulebisatvis (cxrili 2). Tu am programebs SevadarebT saertasoriso sivrcesi moqmed farmaciis 206

207 saganmanatleblo programebtan, natlad davinaxavt, rom garkveuli xarvezebi namdvilad arsebobs. cxrili 2. umarlesi farmacevtuli ganatlebis Tanamedrove kerebi saqartvelosi # umarlesi saganmanatleblo dawesebulebis dasaxeleba Ffarmacii s sabakalav ro programa Ffarmacii s samagistr o programa 1 ssip Tbilisis saxelmwifo samedicino 3 4 universiteti 2 ssip akaki weretlis saxelmwifo universiteti ssip batumis S. rustavelis saxelmwifo 1 universiteti 4 ssip saqartvelos teqnikuri universiteti a(a)ip SoTa mesxias zugdidis saxelmwifo 1 saswavlo universiteti 6 a(a)ip soxumis saxelmwifo universiteti 1 7 Sps Tbilisis samedicino saswavlo universiteti 1 1 `hipokrate~ 8 Sps saqartvelos ilia WavWavaZis saxelobis saertasoriso samecniero-kulturulsaganmanatleblo kavsiri `sazogadoeba codna~ 1 9 Sps kavkasiis saertasoriso universiteti 1 10 Sps suxisvilis saswavlo universiteti 1 11 Sps zugdidis damoukidebeli universiteti 1 A arc diplomamdel da arc diplomissemdgom farmacevtul ganatlebasi CarTuli ar aris saqartvelos Sromis, janmrtelobisa da socialuri dacvis saministro institucia, romelic unda aregulirebdes am dargis saertasoriso donis specialistebis momzadebas. Ees procesi mxolod saganmanatleblo dawesebulebisa da ramdenime msxvili farmacevtuli firmis `ketil nebazea~ mindobili. saxelmwifo unda itvaliswinebdes, rogorc jandacvis msoflio organizaciis, aseve farmacevtta saertasoriso federaciis mititebebsa da gzamkvlevebs, mat mier gamocemul dokumentebs da nergavdes mat qveyanasi kvalificiuri kadrebis mosamzadeblad, romlis safuzveli diplomamdeli ganatlebaa, xolo udao ganmapirobebeli, `uwyveti farmacevtuli ganatleba~. arsebul mdgomareobas amzafrebs is, rom `farmacia~, rogorc adamianis janmrtelobis xelissemwyobi ert-erti umnisvnelovanesi dargi, ar regulirdeba saxelmwifo doneze masin, roca saqartvelos konstituciasi Cawerilia: `saxelmwifo akontrolebs janmrtelobis dacvis yvela dawesebulebas, samkurnalo sasualebata warmoebas da am sasualebebit vawrobas~ (saq. Kkonstitucia, muxli 37. p.p ). ganvitarebuli saxelmwifoebis konstituciebsi, farmacia ara mxolod biznesi, aramed regulirebadi profesiaa. jmo-m msoflio xalxebis janmrtelobis marali donis mirwevisatvis 1998 wels SeimuSava strategia, `janmrteloba yvelasatvis 21-e saukunesi~. janmrteloba ariqmeba, rogorc adamianuri ganvitarebis umtavresi komponenti. arnisnuli strategia itvaliswinebs adamianta janmrtelobisa da sicocxlis iseti xarisxis mirwevas, romelic SesaZleblobas miscems yvela adamians icxovros srulfasovani cxovrebit. 207

208 WHO-s (jmo) miznidan gamomdinare, misi ZiriTadi funqciebia: janmrtelobis dargsi SeimuSaos mtkicebulebebze damyarebuli standartebi, gzamkvlevebi da rekomendaciebi. saqartvelo jmo-s wevria 1992 wlidan. mastan TanamSromlobis strategiis WHO Country Cooperation Strategy" (CCS) farglebsi dadebuli orwliani xelsekrulebis (Biannual Collaborative Agreement, BCA) mixedvit wlebsi jmo-is evropis regionuli biuro daexmareba saqartvelos jandacvis sistemas sxva ZiriTadi sakitxebis paralelurad gaazlieros farmacevtuli seqtoric [6-10]. farmacevtuli bazari permanentulad cvalebadi warmonaqmnia, axali preparatebit, axali teqnologiebit. Eelvis siswrafit vitardeba bioteqnologia, icvleba mkurnalobis metodebi - farmacevtebis kvalifikaciaze ki saxelmwifo ar zrunavs, qveyanasi ar arsebobs kvalifikaciis asamarlebeli kursebi; rac mtavaria, ar arsebobs kadrebis uwyveti gadamzadebis aucilebeli motxovna. farmacevtuli ganatleba unda izleodes pacientze orientirebuli saqmianobis garantias. Sesabamisad, am processi kompetenciis farglebsi unda monawileobdes saxelmwifo, romelic kanonebit daaregulirebda farmacevtul saqmianobas, romlis upirobo mizania mosaxleobas miawodos efeqturi, usafrtxo, xarisxiani da xelmisawvdomi samkurnalo sasualebani. aqedan gamomdinare, sawiroa maregulirebel dokumentebsi dargis specifikuri Taviseburebebisa da im rekomendaciebis satanadod gawera da gatvaliswineba, romeltac gvtavazoben jmo da farmacevtta saertasoriso federacia. amrigad, davaskvnit: farmacevtuli saqmianoba aris socialurad orientirebuli, marali riskis, sazogadoebisatvis safrtxis Semcveli dargi, romelic dakavsirebulia adamianis janmrtelobastan. Aamitom jandacvis msoflio organizacia farmacias Tvlis regulirebad profesiad da es momenti aucilebelia gamoyenebul iqnas farmacevtuli ganatlebis, mat Soris, diplomamdeli da diplomissemdgomi ganatlebis sistemis mowyobasi. literatura 1. n. abulaze. Ffarmacia dasavlet saqartvelosi wlebsi. qutaisi. akaki weretlis saxelmwifo universitetis gamomcemloba: 2013; m. Sengelia. qartuli medicinis istoria. Tb.: b. WumburiZe. farmacevtta samecniero sazogadoeba. Tb.:^ Арзамасцев А.П., Битерякова АМ. Основные направления развития высшего фармацевтического образования. Фармация 2002; 3: Петров В.И., Луцевич А.Н., Решетько О.В. Новые технологии, регулирование и фармакоэко-номика в сфере обращения лекарственных средств. М.: Медицина; 2006: Надлежащая практика фармацевтического образования GPEP reziume qartuliffarmacevtuli ganatlebis zogierti sakitxi abulaze n., alavize n. j. akaki weretlis saxelmwifo universiteti, qutaisi, saqartvelo 208

209 farmacevtul ganatlebas saqartvelosi mdidari tradicia aqvs, romelic moitxovs gagrzelebas, rata pasuxobdes Tanamedrove gamowvevebs. amjamad saqartvelosi 21 akreditebuli farmacevtul-saganmanatleblo programaa, mat Soris 14 sabakalavro da 7 samagistro, romelta done srulad ver akmayofilebs jmo da farmacevtta saertasoriso federaciis mier saertasoriso farmacevtuli ganatlebisadmi wayenebul ZiriTad motxovnebs. Sesabamisad, farmacevtuli ganatleba, iseve rogorc mteli dargi, moitxovs saxelmwifo regulirebas. SUMMARY SOME ISSUES OF THE GEORGIAN PHARMACEUTICAL EDUCATION Abuladze N., Alavidze N. Akaki Tsereteli State University, Kutaisi, Georgia Pharmaceutical Education in Georgia has a rich traditions, which needs to be continue and at the same time it should respond to the current challenges. Presently here there are 21 pharmaceutical accredited educational programs, including 14 Bachelor, 7 Master programs. Their LOS (Level of Significance) do not completely satisfy the requirements of the general principles offered by International Pharmaceutical Education, which are set by WHO and the International Federation of Pharmacists. So, the pharmaceutical education requires government regulation, as all pharmacy industry. USING H-CLINOPTILOLITE AS A SORBENT FOR PLASMA PURIFICATION IN CHEMICAL-TOXYCOLOGYCAL ANALYSIS Halkevych I. Danylo Halytsky Lviv National Medical University, Department of Toxicological and Analytical Chemistry Solid-phase extraction (SPE) techniques widely are used for toxic substances concentrating and complicated biological matrices purification in chemical-toxicological analysis. Synthetic sorbents modified with specific reactive are commonly used for the selective adsorption of substances in accordance to their physical and chemical properties. Their sorption ability decreases and the modifier reactant washing out them in strong acidic media. Natural sorbents, including zeolites, also have the high rate of sorption equilibrium setting, resistance to aggressive environments, thermal stability, ability for regeneration and low cost. One of them is Clinoptilolite. This sorbents is a zeolite of the natural heulandite group. Clinoptilolite is a microporous crystalline hydrated aluminosilicate mineral characterized by cage-like structure and known composition, with high internal and external surface areas, and high cation exchange capacity. Large deposits of natural clinoptilolite are located in Transcarpathian region of Ukraine. This sorbent are used for adsorption cations of metals, gases and catalysis support and it was not used in forensic chemical analysis for preparation and purification of probes obtained during toxic substances isolation from biological samples. Our studies demonstrate that natural clinoptilolite are efficient absorbent for separation and purification of pharmaceutically active compounds. This sorbent have large cation exchange capability and molecular sieves effect and can used for concentrating and separation of high specifity organic compounds with basic and acidic properties in their mixtures with proteins, fats and other organic species contaminations as well as electrolytes. 209

210 We used bupropion as an example of biologically active compound for evaluation of HPLC-UV assay for its detection development. Bupropion is antidepressant, overdose of which is accompanied with toxic effects, often fatal. The study was focused on the sorption of bupropion micro amounts introduced into plasma by zeolite. The bupropion removal percentage affecting with protein contaminations and trace endogenous substances in the biological fluids was also evaluated. The clinoptilolite samples were obtained from the Sokyrnytsia deposits in Transcarpathian region (Ukraine, TU , ). Chemical composition of the clinoptilolite samples was determined as SiO %; Al 2 O %; Fe 2 O 3 0.9%; TiO 2 0.5%; CaO 3.44%; MgO 0.68%; P 2 O %, K 2 O-Na 2 O 3.03% by mass, respectively; mass ratio SiO 2 /Al 2 O 3 was 5.5. It was found that sorption ability of modified clinoptilolite was enhanced. Analytical purity HCl was used to treat clinoptilolite and to modify it with H + ions. The clinoptilolite modification with H + ions was achieved by the samples treatment with 1 M HCl solution. Adsorption properties of H-clinoptilolite were determined in dynamic conditions using SPE technique. SPE cartridges were filled by 0,6 g of H-clinoptololite with the particles size mm. Before testing the cartridges were firstly rinsed with 2 ml of 0.1 M HCl solution in methanol and 2 ml of distilled water. Various amounts of bupropion solution were added to 4 ml of plasma. Bupropione solutions concentrations were set in the range of its therapeutic dose ( mg/l), toxic dose ( mg/l) and fatal dose 0.45 mg/l. All plasma volume was injected through zeolite packed cartridges at a flow rate of 0.5 ml/min. Cartridges were firstly rinsed with 4 ml of water and 3 ml of water-methanol solution (1:1). Sorbent was dried in a stream of nitrogen and bupropion was eluted with 3 ml of 0.1 M HCl solution in methanol. Methanol elutes were dried in the stream of nitrogen, quantitatively dissolved in 200 µl of methanol and were then subjected to HPLC analyzing (chromatograph Waters 2690 Separation Module, UV diode array detector Waters 996, ACE 5 C18 column, mobile phase consisted of acetonitrile (solution A) 0.05% aqueous solution of tetrafluoroacetic acid (TFA, solution B). The mobile phase flowed in gradient mode. The solutions A and B volumes ratio was 95:5 for the first 2 min, 45:55 during next 20 minutes, 10:90 between 23 and 24 minutes, and 95:5 during 3 final minutes. The volume of the injected sample was 10 µl, the mobile phase flow rate was 1 ml/min. Bupropion was identified by UV spectrum at 248 nm in accordance to its retention time (12.277±0.051 min). The amount of the adsorbed bupropion was determined with calibration curve: Y= Х , with the correlation coefficient r 2 = In blank samples which served as backgrounds during the analysis obtained by passing water and plasma through the clinoptilolite any peaks with similar to bupropion retention parameters were not found. Protein contaminations did not affect the bupropion elution profiles. The obtained results proved bupropion percentage removal on H- modified clinoptilolite packed column from plasma at the level of while the relative standard deviation (RSD) did not exceed 2.47%. Conclusions. H-clinoptilolite was assayed as the efficient sorbent for solid phase extraction of bupropion from plasma and its HPLC-UV detection in chemical-toxicological analysis. The capacities of bupropion extraction from plasma were 74-79% with the RSD under 2.47%. The optimal conditions for bupropion separation using ACE 5 C18 column and its HPLC-UV analytical detection at λ = 248 nm were developed. The relative error of bupropion quantitative determination in its solutions was 1.27%. cofis epidemiologia saqartvelosi Tanamedrove etapze mwedlisvili i., gelovani d., juluxaze j., CoCiSvili r. Tbilisis saxelmwifo samedicino universiteti, sazogadoebrivi janmrtelobis departamenti, epidemiologiisa da biostatistikis mimartuleba, saqartvelo cofi ert-erti yvelaze mnisvnelovani infeqciuri daavadebaa, rac ganpirobebulia SemdegiT: daavadeba gvxvdeba 150-ze met qveyanasi; cofi potenciur safrtxes uqmnis 210

211 aziis da afrikis mkvidr 3,3 miliardze met adamians; yovelwliurad am daavadebit daaxloebit 55 atasi adamiani kvdeba msofliosi; cofze saewvo cxoveltan kontaqtirebul pirta 40% 15 wlamde asakis bavsvia; daavadebis ganvitarebis SemTxvevaSi letalobis macvenebeli 100%-ia [4]. kvlevis mizani: cofis epidemiologiuri Taviseburebebis Seswavla saqartvelosi da daavadebis gavrcelebis xelsemwyobi faqtorebis analizi. kvlevis masala da metodebi. arnisnuli miznis Sesasruleblad SeviswavleT daavadebata kontrolisa da sazogadoebrivi janmrtelobis erovnul centrsi arsebuli statistikuri masala cofit avadobis Sesaxeb, romelic moicavda wlebs. cofit dainficirebis mizezebis dadgenisatvis SeviswavleT wlebsi am daavadebit Sepyrobil pirta avadmyofobis istoriebi da keris epidemiologiuri kvlevis baratebi. mirebuli monacemebi davamusavet Epi info-s sasualebit. kvlevis Sedegebi da gansja. cofit avadobis dinamika ganxilul iqna wlebsi (cxrili 1). SemTxvevaTa maqsimaluri raodenoba saqartvelosi 2007 wels dafiqsirda. gamovlinda daavadebis 10 SemTxveva da avadobis macvenebelma 100 atas mcxovrebze 0,22 Seadgina, rac migvacnia, rom sakmaod marali macvenebelia. SedarebisaTvis arvnisnavt, rom rusetis federaciasi, romlis mosaxleoba, daaxloebit, 145 milions udris, daavadebis maqsimaluri raodenobaa cxrili 1. cofit avadobis dinamika saqartvelosi wlebsi weli SemTxvevaTa raodenoba macvenebeli 100 atas mcxovrebze 0,16 0,22 0,16 0,14 0,11 0,07 0, wels ariricxa - 22, ramac avadobis macvenebelsi 0,015 0 / 0000 Seadgina wlebsi ki sul 57 SemTxveva gamovlinda [1], anu weliwadsi sasualod 14 SemTxveva (macvenebeli - 0,001 0 / 0000 ). saqartvelosi 2007 wels cofi ufro intensiurad iyo gavrcelebuli, vidre, magalitad, CrdiloeT afrikis qveynebsi. sabednierod epidsituacia, bolo wlebsi, uketesobisken Seicvala da 2012 wlebsi qveyanasi daavadebis mxolod 3-3 SemTxveva gamovlinda da macvenebeli 0,07-mde Semcirda. daaxloebit analogiuri mdgomareoba aris TbilisSi. yvelaze meti SemTxveva 2009 wels dafiqsirda 3 (avadobis macvenebeli 0,26 0 / 0000 ) wlebsi ki saqartvelos dedaqalaqsi cofis arc erti SemTxveva arar gamovlenila. daavadeba aratanabrad aris gavrcelebuli saqartvelos regionebsi. yvelaze xsirad cofi imeretsi da samegrelosi gvxvdeba, sadac wlebsi daavadebis 4-4 SemTxveva ariricxa. arnisnul periodsi cofis arc erti SemTxveva ar yofila guriis, awaris, samcxe-javaxetis, mcxeta-mtianetis regionebsi. sainteresoa, Tu vin iyo daavadebuli adamianisatvis infeqciis wyaro wlebsi qveyanasi daavadebis 11 SemTxveva gamovlinda. ert SemTxvevaSi wyaro ver iqna dadgenili, radgan pacientma ver gaixsena Tu rodis da romelma cxovelma ukbina. danarcen 10 SemTxvevaSi infeqciis wyaro iyo ZaRli (80%). 4 SemTxvevaSi es iyo mawanwala ZaRli. 2 SemTxvevaSi adamiani dakbina mezoblis ZaRlma da aseve 2 SemTxvevaSi sakutarma ZaRlma (cxrili 2). erti adamiani 211

212 cxrili 2. cofis infeqciis wyaro wlebsi (11 SemTxveva) ZaRli sxva infeqciis wyaro SemTxvevaTa raodenoba mawanwala ZaRli 4 sakutari ZaRli 2 mezoblis ZaRli 2 sakutari kata 1 tura 1 ucnobia 1 dainficirda sakutari katis mier dakbenis Sedegad da mxolod ert adamians ganuvitarda cofi gareuli cxovelis mier dakbenis Sedegad. qvemo qartlsi, erovnebit azerbaijaneli moqalaqe dakbina turam. Cveni monacemebi emtxveva sxva qveynebis monacemebs, romelta Tanaxmad cofis dros wamyvani infeqciis wyaroa ZaRli. gansxvavebuli mdgomareobaa mxolod rusetis federaciasi, sadac SemTxvevaTa 43%-Si daavadeba ganvitarda gareuli cxovelebis dakbenis Sedegad [1]. Cven gavaanalizet, Tu ram gamoiwvia am TerTmeti adamianis daavadeba cofit. mizezi yoveltvis iyo erti - cxovelebis mier dakbenis Semdeg dazaralebuli adamianebi ar mimartavdnen samedicino dawesebulebas da bunebrivia, mat ar utardebodat antirabiuli specifikuri profilaqtika. gamonaklisi iyo mxolod erti SemTxveva wlis 14 dekembers Tbilisis infeqciuri patologiis centrsi motavsda avadmyofi, 11 wlis, mcxovrebi q. TelavSi. 1 dekembers bavsvi sakutarma ZaRlma dakbina saxis aresi da marjvena zeda kiduris TiTebze. Wriloba adgilobrivad daumusava dedam da 4 dekembers mat mimartes Telavis raionis saavadmyofos antirabiul kabinets, sadac bavsvs daenisna cofis sawinaarmdego acrebi. mas vaqcina gauketda 3-jer: 4, 7 da 11 dekembers, imave dris saramos daewyo daavadeba, ris gamoc igi hospitalizebul iqna TbilisSi. miuxedavad imisa, rom Wrilobebis lokalizaciidan gamomdinare, advili savaraudo iyo, rom mokle inkubaciuri periodi iqneboda, eqimma bavsvs mainc ar gauketa cofis sawinaarmdego specifikuri imunoglobulini, rac gaxda bavsvis daavadebis da gardacvalebis mizezi. cofit daavadebulta asakobrivi struqturis Seswavlam gvicvena, rom daavadeba ZiriTadad aqtiuri asakis pirebis xvedria wlebsi saqartvelosi cofit daavadebis SemTxvevebis 65,9% wlis asakis pirebze modis, rac albat, kanonzomieri movlenaa, radgan swored am asakis adamianebs uwevt yvelaze xsirad kontaqti cxovelebtan, rogorc SinaurTan, ise gareultan. sakmaod maralia xansisesuli asakis pirebis xvedriti wili avadobasi 19,5%. sabednierod, gansxvavebit mravali qveynisagan [3], saqartvelosi bavsvebi cofit isviatad avaddebian. saanalizo periodsi 4 wlamde asakis bavsvebsi daavadebis arc erti SemTxveva ar dafiqsirebula wlis asakis bavsvebsi ki cofis 3 SemTxveva ganvitarda. arsanisnavia, rom yvela es SemTxveva dakavsirebulia sakutar an mezoblis ZaRlTan kontaqtit. amdenad, Zalian didi mnisvneloba eniweba yvela Sinauri ZaRlis da katis acras antirabiuli vaqcinit. rogorc mosalodneli iyo, cofit saqartvelosi ZiriTadad mamrobiti sqesis pirebi xdebian avad. saanalizo wlebsi SemTxvevaTa 73,2% swored matze modioda. anu, qalebtan SedarebiT kacebi 3-jer ufro xsirad xdebian avad am daavadebit. unda itqvas, rom saqartvelosi mosaxleobisatvis antirabiuli daxmareba sakmaod intensiurad xorcieldeba, razec miutitebs cxrilsi #3 moyvanili monacemebi. rogorc vxedavt, 2012 wels adamians armoucines es daxmareba, ramac macveneblebsi Seadgina / unda arinisnos, rom regionebsi, am kutxit, met-naklebad aris gansxvaveba. yvelaze dabali macvenebelia qvemo qartlsi 664,8 0 / 0000, samcxe-javaxetis 212

213 regionsi - 692,3 0 / 0000 da awarasi 736,8 0 / masin, rodesac samegrelosi es macvenebeli arwevs 1518,9 0 / s, Sida qartlsi ,5 0 / s da imeretsi 1664,5 0 / s. am macveneblebit saqartvelos wamyvani adgili ukavia mtel msofliosi. arc ert qveyanasi ase intensiurad ar xorcieldeba mosaxleobis imunizacia antirabiuli vaqcinit [2]. saqme gvaqvs paradoqsul situaciastan. Zalian xsirad adamians ar swirdeba cofis vaqcinis gaketeba, magram pirovnebis dajinebuli motxovnit igi mainc ketdeba. masin rodesac, isini, visac aucileblad unda Cautardes antirabiuli daxmareba, xsirad arc ki midian samedicino dawesebulebasi. Cveni azrit, aucilebelia mosaxleobis meti informireba cofis, kerzod ki misi gadacemis gzebisa da profilaqtikis Taobaze. cxrili 3. antirabiuli daxmarebis macvenebeli saqartvelosi 2012 wels regionebi raodenoba Tbilisi ,4 0 / 0000 awara ,8 0 / 0000 kaxeti / 0000 imereti ,5 0 / 0000 samegrelo ,9 0 / 0000 Sida qartli ,5 0 / 0000 qvemo qartli ,8 0 / 0000 guria ,1 0 / 0000 samcxe javaxeti ,3 0 / 0000 mcxeta-mtianeti ,7 0 / 0000 rawa-lecxumi ,7 0 / 0000 sul ,9 0 / 0000 adamianebisatvis antirabiuli daxmareba yvelaze xsirad ZaRlis mier dakbenis SemTxvevaSi xorcieldeba wlebis monacemebit 78,9% SemTxvevaSi Wriloba miyenebuli iyo ZaRlebis mier. adamianebs xsirad kbens katac. 16,8%-Si adamianebs swored katis nakbenis gamo CautardaT Sesabamisi daxmareba. Zalian dabalia sxva cxovelebisa da mrrrnelebis roli. mxolod 4,3%-Si miires adamianebma matgan dazianeba. daaxloebit analogiuri situaciaa TbilisSi. Tumca mtlianad QქveyanasTan SedarebiT ufro dabalia ZaRlis roli da momatebulia katebis mnisvneloba (p<0,05-ze). sainteresoa, rom TbilisSi saqartvelostan mimartebasi ufro maralia sxva cxovelebis roli (6,0% da 4,3% Sesabamisad). amrigad, cofi saqartvelosi jer kidev fartod aris gavrcelebuli. Zalian xsiria rogorc adamianebis dakბenis SemTxvevebi, ise mattvis antirabiuli daxmarebis Catarebis macvenebeli. Cveni azrit, sawiroa gaizardos ZaRlebisa da katebis antirabiuli vaqcinit acrebis macvenebeli, rac Tavis mxriv Seamcirebs rogorc cofis SemTxvevebis raodenobas adamianebsi, ise antirabiuli daxmarebis odenobas. literatura 1. Постановление Главного государственного санитарного врача Российской Федерации от 1 февраля 2012г. 13. «Об усилении мероприятий, направленных на профилактику бешенства в Российской Федерации». 2. Annual epidemiological report Rabies. 3. WHO. Expert consultation on rabies. World Health Organ Tech. Rep. Ser., 2005, 931, WHO. Wkly Epidemiol. Rec., 2010, 85 (31),

214 reziume cofis epidemiologia saqartvelosi Tanamedrove etapze mwedlisvili i., gelovani d., juluxaze j., CoCiSvili r. Tbilisis saxelmwifo samedicino universiteti, sazogadoebrivi janmrtelobis departamenti, epidemiologiisa da biostatistikis mimartuleba, saqartvelo Seswavlil iqna cofis epidemiologia saqartvelosi wlebis monacemebis safuzvelze. avadobis yvelaze marali done dafiqsirda 2007 wels 0, atas mcxovrebze, rac sakmaod marali macvenebelia. gansakutrebit gavrcelebuli iyo daavadeba imeretisa da samegrelos regionebsi. yvelaze xsirad infeqciis wyarod cofiani ZaRli gvevlineboda, gansakutrebit ki mawanwala ZaRlebi. qveyanasi Zalian maralia antirabiuli daxmarebis macveneblebi wels man Seadgina 1148,9. miuxedavad amisa, adamianebsi cofis ganvitarebis ZiriTadi mizezia Sesabamis pirebsi satanado antirabiuli daxmarebis ar Catareba. SUMMARY RABIES EPIDEMIOLOGIC CHARACTERISTICS AT THE MODERN STAGEIS IN GEORGIA Mchedlishvili I., Gelovani D., Djulukhadze Dj., Chochishvili R. Tbilisi State Medical University, Public Health Department, Division of Epidemiology and Biostatistics, Georgia Epidemiologic characteristics of rabies for a period were studied in Georgia. The highest incidence rate per population revealed in 2007, which is significantly high. The infection mostly was distributed in Imereti and Samegrelo regions. Infected dogs and especially vagrant dogs were identified as sources of infection. Rate of medical services against rabies is very high in the country; it was 1148,9 0 / 0000 in Although the main cause of developing of rabies among humans is not giving appropriate services to target groups. kvebiti qcevis cvlilebebis daxasiateba sxvadasxva konstituciis, sxeulis wonisa da arteriuli wnevis jgufebsi darsania T., sazogadoebrivi jandacvis akademiuri doqtori, yurasvili b., medicinis akademiuri doqtori Tbilisis saxelmwifo samedicino universiteti, kvebisa da asakobrivi medicinis mimartuleba Tanamedrove warmodgenebit konstitucia ar aris statikuri movlena, ucvladi da winaswar mkacrad gansazrvruli. is yalibdeba, realizdeba da SesaZlebelia Seicvalos garemos gavlenit [1]. arsebobs mteli rigi kvlevebi konstituciis sxvadasxva daavadebebtan, fsiqikur funqciebtan, qcevit reaqciebtan urtiertkavsirebis Sesaxeb, mag., problema `konstitucia da profesia~ [2]. amastanave, ucxouri Tu qartuli medicinis dargis samecniero literaturasi Cven ver armovacinet monacemebi adamianis kvebit qcevebsa da konstituciur Taviseburebebs Soris kavsiris arsebobaze. kvlevis masala da metodebi. kvleva Catarda saqartvelos masstabit. kvebiti qcevis higienuri SefasebisaTvis SeirCa izulebit gadaadgilebuli pirebi afxazetidan da 214

215 samacablodan, agretve, studentebi umarlesi saswavleblidan, sajaro skolebis maswavleblebi, adamianebi, romelta Tviuri Semosavali iyo 1000 larze meti, pensionrebi. izulebit gadaadgilebulta Soris SerCeul iqna adamianebi, romlebic cxovrobdnen kompaqturad, iyvnen droebit umusevrebi da Rebulobdnen saxelmwifo daxmarebas 22 laris odenobit. jgufebi daiyo asakisa da ganatlebis mixedvit. umarlesi ganatleba hqonda _ 72,8%-s, sasualo _ 27,1%-s, ojaxuri mdgomareobis mixedvit gamoiyo 2 jgufi: daojaxebuli _ 72,2%, martoxela _ 27,8%. Cven gamoviyenet kvebiti driuris Sevseba, sadac gamokitxulebi arnisnavdnen Svidi dris manzilze mirebul kerzebsa da produqtebs. masalebi gaanalizebuli iyo specialuri kompiuteruli programis mier, romlis monacemta bazas warmoadgenda informacia sakvebi produqtebisa da kerzebis energetikul Rirebulebasa da qimiur Sedgenilobaze [4], kulinaruli damusavebisas sakvebi nivtierebebis danakargis gatvaliswinebit. racionebis energetikuli Rirebuleba da qimiuri Sedgeniloba fasdeboda im kriteriumebis mixedvit, romelic dadgenilia mosaxleobis sxvadasxva jgufisatvis energiasa da sakveb nivtierebata fiziologiuri motxovnilebebis normebit [3]. Semdgom etapze xdeboda kvebiti statusis zogierti komponentis Sefaseba. energiis adekvaturi miwodebis ZiriTadi kriteriumi aris sxeulis masis indeqsi _ ketles indeqsi (smi) - kvebiti statusis ert-erti mnisvnelovani macvenebeli [5]. gamotvla sxeulis wona (kg) Catarda formulit: smi = smi 25,0-30,0 gulisxmobs Warbi wonis 2 simarle (sm) arsebobas; smi 30,0-ze meti ganixileba rogorc simsuqne. kvebis gaumjobesebastan dakavsirebuli RonisZiebebis ganxorcieleba moitxovs mosaxleobis janmrtelobis mdgomareobasa da calkeuli regulatoruli da eferentuli sistemebis funqciebis mdgomareobaze informaciis mirebas. amastan dakavsirebit Seswavlil iqna arteriuli hipertenziis, Warbi wonisa da simsuqnis gavrceleba sxvadasxva kvebiti qcevis upiratesi formebisa da fsiqologiuri tipebis mqone pirebsi. arteriuli hipertenziis arsebobaze saubrobdnen arteriuli wnevis macveneblebis sididit, dadgenili janmoti (diast. art. wn. > 90 mm vercx. sv. /sist. art. wn. >140 mm vercx. sv.). Seuswavleli rceba ama Tu im kvebiti qcevis formebis Camoyalibebis problema sxvadasxva konstituciis mqone pirebsi. amastan dakavsirebit yvela gamokitxuli iyo ganawilebuli sam konstituciur jgufsi: normosteniuri, asteniuri, hipersteniuri. ganawilebis raodenobriv kriteriumad micneuli iyo pinies indeqsi: pinies indeqsi =sxeulis sigrze _ (sx. wona+gulmkerdis garsemoweriloba simsvidesi). yvela gamotvla ganxorcielda SPSS14 programit. kvlevis Sedegebi da gansja. kvlevis Sedegad armocnda, rom hipersteniuri konstituciis mqone pirebsi ufro xsirad arinisneboda kvebiti qcevis emociogenuri tipi (16,8%). asteniurebsi emociogenuri tipi gvxvdeboda 7,3%-Si. eqsternuli tipis farto gavrceleba damaxasiatebelia rogorc hipersteniurebisatvis, aseve asteniurebisatvis normosteniurebtan SedarebiT. kvebiti qcevis eqsternuli darrvevebis mqone pirebi Rebulobdnen met energias dris manzilze sxvebtan SedarebiT. Tumca hipersteniurebi ufro midrekilni arian simsuqnis ganvitarebisken, vidre asteniurebi. magram cnobilia, rom asteniuri konstituciis pirebsi ZiriTadi cvlis done ufro maralia, vidre hipersteniurebsi. Sesabamisad, mraval asteniursi energiis siwarbe sasualo normastan SefardebiT iyo nakleb gamoxatuli, vidre hipersteniurebsi, romlebsac ZiriTadi cvla ufro dabali aqvt. 215

216 Warbi sxeulis wonis jgufsi (smi ) Zalian xsirad Rebulobdnen sakvebs (48,1%). kvebiti qcevis fsiqologiur TaviseburebebTan sxeulis masis indeqsis urtiertkavsiris Sefasebam acvena (nax. 1), rom yvelaze naklebi gadaxra iyo normaluri sxeulis masis mqone pirta jgufsi. darrvevebi xsiri iyo Warbi wonis mqone pirebsa (45,5%) da msuqnebsi (45,5%). normaluri wona racionalu ri 70,5% emociogenu ri 0,9% eqsternalu ri 10,3% SezRuduli 0,9% Warbi wona simsuqne racional uri 45,5% emociogen uri 19,8% racional uri 45,5% emociogen uri 22,3% eqsternal uri 28,3% SezRudul i 12,4% nax.1 sxeulis sxvadasxva wonis mqone pirta Soris kvebiti qcevis fsiqologiuri Taviseburebebis tipebis gavrceleba Tumca kvebiti qcevis cvlilebebis struqtura mat Soris iyo gansxvavebuli. WarbwonianebSi ufro xsirad gvxvdeboda eqsternuli tipi. gamoxatuli simsuqnisas 3- jer xsiri iyo emociogenuri tipi. zomieri uaryofiti emociuri gancdebis drosac ki mat esawiroebodat sakvebis damatebit mireba. msuqnebsi ufro xsirad iyo gavrcelebuli SezRuduli tipi, radganac mat swirdebodat damatebiti nebisyofa sakvebis mirebis SezRudvisTvis. mat Soris ufro isviatad, vidre WarbwonianebSi, gavrcelebuli iyo kvebiti qcevis eqsternuli varianti. radganac emociuri cvlilebebis ganvitarebis ert-ert mizezs warmoadgens serotoninis cvlis darrveva, Warbwonianebi da msuqnebi gazrdili emociuri fonis periodsi iyenebdnen `waxemsebis~ saxit naxsirwylebis Semcvel produqtebs. eqsternuli tipis mqone pirebi arnisnavdnen, rom sakmaod xsirad Rebulobdnen sakvebis did raodenobas saramos periodsi, amastan Wamdnen am periodsi ramdenjerme. aseti kvebiti qceva SinaarsiT iyo relaqsaciis forma. cnobilia, rom kvebiti darrvevebi SesaZloa iwvevdes sxvadasxva daavadebas, mat Soris arteriul hipertenzias. ar aris Seswavlili sakitxi imis Sesaxeb, axdens Tu ara gavlenas kvebiti qcevis fsiqologiuri Taviseburebebi am sindromis gavrcelebaze. amastan dakavsirebit ganxiluli iyo arteriuli hipertenziis SemTxvevaTa sixsire kvebiti qcevis cvlilebebis sxvadasxva fsiqologiur tipta jgufsi (nax. 2). 216

217 gamokitxulta Soris 32,1%-s hqonda momatebuli arteriuli wneva. mati raodenoba arsebitad gansxvavdeboda kvebiti qcevis fsiqologiuri tipebis jgufebsi. yvelaze xsirad arteriuli hipertenziis SemTxvevebi arinisneboda kvebiti qcevis darrvevebis eqsternuli tipis mqone adamianebsi (39,8%). rogorc arvnisnet, adamianebi kvebiti qcevis aseti tipis darrvevebit Rebulobdnen met energetikur wyaros, cximebs, martiv naxsirwylebs. mat Soris gvxvdeboda WarbwonianTa da msuqanta yvelaze didi raodenoba. amas SeeZlo gavlena moexdina arteriuli hipertenziis sixsireze. SedarebiT naklebi (36,9%) raodenobit marali arteriuli hipertenziis mqone pirebi iyo emociogenuri tipis jgufsi. emociuri labiluroba, SfoTvis gacilebit marali done armocnda arsebiti arteriuli hipertenziis sixsiris momatebistvis nax. 2 arteriuli wnevis sxvadasxva donis mqone pirta Soris kvebiti qcevis fsiqologiuri Taviseburebebis daxasiateba cnobilia, rom arteriuli hipertenziis ganvitarebasi gansazrvrul rols TamaSobs kvebis Taviseburebebi. amastan dakavsirebit Seswavlil iqna kvebiti upiratesobebi pirebsi, rogorc normaluri wnevit, aseve arteriuli hipertenziit. am jgufebsi iyo meti adamiani, romelic upiratesobas xorcis (32,9% da 24,5% Sesabamisad), rzis (13,8% da 8,5%), martivi naxsirwylebis Semcvel (8,3% da 4,1%) da Zliercximian (14,1% da 10,3%) produqtebs aniwebda upiratesobas. amave dros, mat Soris gacilebit naklebi raodenobit iyvnen pirebi, romelta racionsi dominirebda rtuli naxsirwylebis Semcveli produqtebi (24,3% da 41,3%) da bostneuli (4,8% da 9,5%). sxvadasxva wonis mqone pirta kvebit racionsi Warbobda produqtta sxvadasxva jgufebi. Warbwonianebi ufro etanebodnen Zliercximian produqtebsa (16,8%) da purfuntuseuls (41,5%). zemotqmulidan gamomdinare SeiZleba davaskvnat: mosaxleobis mier kvebis produqtebis mirebis makrostruqturaze garda demografiuli, socialur-ekonomikuri, sawarmoo faqtorebisa, gavlenas axdens kvebiti qcevis fsiqologiuri cvlilebebi da medikobiologiuri mdgomareobis Taviseburebebi, romelic ganapirobebs energiis Warb mirebas, sakvebi nivtierebebis arabalansirebulobas, cxoveluri cilebis, vitaminebis, mikroelementebis arasakmaris, xolo najeri cximovani mjavebis, qolesterinis Warb mirebas. literatura 1. Гичев Ю.П., Гичев Ю.Ю. Общие представления о биологической и фармакологической активности микронутриентов. Введение в общую микронутриентологию. Новосибирск: 1998; Горбатовский М.А. Типы конституции у больных инфарктом миокарда. Межд. Конф.: Актуальные вопросы биомедицинской и клинической антропологии. Томск-Красноярск: 1996; Маев И.В., Петухов А.Б., Мартинчик А.Н. и др. Методика изучения фактического питания и освоение практических навыков в клинической оценке состояния питания больного: Учебно-метод. Пособие. М.: 1999;

218 4. Химический состав пищевых продуктов: Справочные таблицы содержания аминокислот, жирных кислот, витаминов, макро-миркоэлементов, органических кислот и углеводов. Под. ред. И.М. Скурихина, М.Н. Волгарова. М.: 1987; Bray G.A. Obesity. Part 1: Patohgenesis. West. J. Med. 1988; 149(4): reziume kvebiti qcevis cvlilebebis daxasiateba sxvadasxva konstituciis, sxeulis wonisa da arteriuli wnevis jgufebsi darsania T., sazogadoebrivi jandacvis akademiuri doqtori, yurasvili b., medicinis akademiuri doqtori Tbilisis saxelmwifo samedicino universiteti, kvebisa da asakobrivi medicinis mimartuleba Tanamedrove warmodgenebit konstitucia ar aris statikuri movlena, ucvladi da winaswar mkacrad gansazrvruli. ucxouri Tu qartuli medicinis dargis samecniero literaturasi Cven ver armovacinet monacemebi adamianis kvebit qcevasa da konstituciur Taviseburebebs Soris kavsiris arsebobaze. cnobilia, rom kvebiti darrvevebi SesaZloa iwvevdes sxvadasxva daavadebas, mat Soris arteriul hipertenzias. kvleva Catarda saqartvelos masstabit. SeviswavleT kvebiti qcevis fsiqologiuri darrvevebi sxvadasxva konstituciis, arteriuli wnevisa da sxeulis wonis mqone adamianebsi. kvlevis Sedegad armocnda, rom mosaxleobis mier kvebis produqtebis mirebis makrostruqturaze garda demografiuli, socialur-ekonomikuri, sawarmoo faqtorebisa, gavlenas axdens kvebiti upiratesobebi, kvebiti qcevis fsiqologiuri cvlilebebi da mediko-biologiuri mdgomareobis Taviseburebebi, romelic ganapirobebs energiis Warb mirebasa da sakvebi nivtierebebis arabalansirebulobas. SUMMARY CHARACTERISTICS OF FOOD BEHAVOR IN GROUPS ACCORDING TO DIFFERENT CONSTITUTION, BODY WEIGHT AND ARTERIAL PRESSURE Darsania T., PH.D., Kurashvili B., PH.D. Tbilisi State Medical University, Department of Nutrition and Ageing Medicine According to modern conception constitution is not invariable and strictly predetermined statistical occurrence. Neither in foreign nor domestic literature of medical branch we could not find data about interrelation between human eating behavior and constitutional features. It is known that feeding disturbances can possibly provoke different diseases and, among them, arterial hypertension. We studies psychological disturbances in people of different constitution, arterial pressure and body weight. The study was conducted in all Georgia. Outcome of the research/study enables us to conclude: besides demographic, social and economic factors macrostructure of foodstuffs consumption of population influences food preferences that make conditional consumption of excessive energy intake, non-balanced animal-albumens, inadequate vitamins, micro elements and abundant consumption of fatty acids and cholesterol. 218

219 spiropiranis micela - cocxal organizmsi samkurnalo preparatis gadamtani nanokonteineri devaze l., maisuraze j., petriasvili g., sefasvili n., zurabisvili c., mjavanaze i., axobaze S. saqartvelos teqnikuri universiteti, v.wavwanizis sax. kibernetikis instituti, saqartvelo nanoteqnologia perspeqtiuli mimartulebaa Tanamedrove mecnierebis yvela dargsi, mat ricxvsi medicinasa da farmaciasi. nanoteqnologia sasualebas gvazlevs vimusaot nanometris, anu ZiriTadi biologiuri struqturebis ujredis, makromolekulebis (dnm, cilebi) zomebis doneze. Nnanomedicina (bioteqnologiisa da nanoteqnologiis gadakveta) tradiciuli medicinis msgavsad moicavs avadmyofobis diagnostikas, mkurnalobas da profilaqtikas nanozomis instrumentebit. nanomedicinis saboloo mizania iseti mkurnali nanorobotebis Seqmna, romlebic gadaadgildebian cocxal organizmsi, gaivlian yvela bariers, miawvdian ujreds wamals da sawiroebis SemTxvevaSi moaxdenen masze manipulacias (mag. qolesterolis danaleqebisgan gasuftaveba). Ee.i. ert nanokompozitur sistemasi gaertianebuli unda iyos transportis, samkurnalo da diagnostikuri Tvisebebi. bevri wamali laboratoriul pirobebsi perspeqtiulia ama Tu im daavadebastan sabrzolvelad, magram organizmsi efeqturad ver arwevs sawiro raodenobit sasurvel dros daavadebul adgils. Aam rtuli amocanis gadawyveta SesaZlebeli gaxda nanoteqnologiis mesveobit. nanonawilakis mag. vezikulis, micelis, fuleronebis, nanomilakebis da sxv. nanokonteinerad gamoyenebit. nanokonteiners unda axasiatebdes Semdegi Tvisebebi: ar unda iyos toqsikuri, Seswevdes unari SeaRwios ujredis membranebsi, unda hqondes antena, anu gare zemoqmedebaze moreagire ubani, romlis sasualebitac ganxorcieldeba mizanmimartuli mozraoba da SigTavsisgan dacla moxdeba sasurvel adgilas sasurvel dros. cxovelebze Catarebuli cdebit dadginda, rom daavadebul adgilze nanokonteinerit miwodebuli wamlis moqmedebis efeqturoba Cveulebrivi ineqciit Seyvanilisas 1-2 rigit aremateba. rac gamowveulia imit, rom Teoriulad gamotvlili samkurnalo moqmedebistvis ineqciit Seyvanili sawiro preparatis raodenoba nawildeba mtel sxeulsi da daavadebul adgils srulad ver miewodeba. yovelive es, garda organizmze mavne zemoqmedebisa, finansebsac ukavsirdeba. aramiznobrivad (mag. QqimioTerapiis dros) ixarjeba Zvirad Rirebuli preparatebi. avtorebis mier sintezirebuli fotoqromuli naertebis - spiropiranebis fizikurqimiuri Tvisebebis Seswavlisas armocenilia movlena _ am naertebit dopirebuli qolesteruli Txevadkristaluri kompoziciis nanonawilakebad-micelebad TviTorganizebis unari [1]. aseti micelebi, rogorc nanokonteinerebi, SesaZlebelia gamoicados cocxal organizmsi wamlis miznobrivad transportirebistvis. spiropiranebi organul fotoqromul, bistabilur naertta mnisvnelovani klasia. bistabilur molekulebs da molekulur ansamblebs SeuZlia garkveuli energetikuli barierit gayofil or Termodinamikurad mdgrad mdgomareobasi arseboba. gadartva ertidan meoresi Ggare stimulirebit (sinatle, sitbo, meqanikuri stresi, eleqtruli da magnituri velebi da sxv.) xdeba. spiropiranis moculobiti arnagobis, Seuferavi, arapolaruli molekula ultraiisferi (ui) sinatlis zemoqmedebit gadadis koplanarul, Seferil, marali dipoluri momentis mqone merocianinul formasi. aseti bipolaruli molekulebi garkveul pirobebsi iolad TviTorganizdeba, warmoqmnis nanonawilakebs. 219

220 spiropiranis molekulebis ultraiisferi sxivebit inducirebisas warmoqmnili merocianinuli koplanaruli, bipolaruli, molekulebi azottan grzeli alkilis radikalis arsebobisas SeiZleba ganvixilot rogorc amfifiluri nawilaki, romelsac marali dipoluri momentis mqone Tavi da arapolaruli, grzeli alkilis radikalis kudi aqvs. P polaruli Tavi Aarapolaruli kudi dasxivebis processi merocianinuli formis molekulebis warmoqmnas da koncentraciis matebas Tan sdevs mati micelebad struqturireba. micelirebis kritikuli koncentracia grzeli alkilis radikalis mqone naertebistvis dabalia, radgan es sidide ukuproporciulia molekulis kudis sigrzisa. fotoinducirebis da micelirebis procesebi arainerciulia, e.i. trigeris CarTvisTanve iwyeba. ZiriTad xsnarsi mikrodoneze warmoiqmneba nanonawilakebi. kvlevebis Sedegad dadgenilia, rom mirebuli nanonawilaki warmoadgens spiropiranis nm zomis micelebs. armocnda, rom ui sinatlit eqspoziciis Sedegad dipoluri momentis mnisvnelovanad gazrdis Sedegad mirebuli merocianinis micela ikumseba, misi zoma orjer naklebi xdeba sawyisi spiropiranis micelis zomaze. E Cveni mosazrebit, mirebuli Sedegebi gamoyenebas hpovebs wamlis mizanmimartul transportirebis saqmesi. Pprocesis dros mirebuli spiropiranis micelebi zemot CamoTvlil yvela motxovnas akmayofilebs: 1) mati zoma ar aremateba 100 nm; 2) spiropirani ara Tu toqsikuria, aramed Sedis zogierti samkurnalo preparatis SemadgenlobaSi [2], 3) qolesterol eterebi ki mravladaa cocxal organizmsi (mag. narveli). 4) micelis Semadgenel molekulebs aqvs antena, romlis mesveobitac sistemaze zemoqmedeba distanciuradaa SesaZlebelia. spiropiranis micela aris Rru, mdgradi garsit daculi e.w. amfifiluri polaruli (hidrofiluri) Tavisa da arapolaruli (hidrofoburi) kudis mqone molekulebisgan Seqmnili sfero. datvirtvis dros hidrofoburi wamali moeqceva micelis RruSi da garsit daculi transportirdeba sisxlit. sawiroebis SemTxvevaSi micelas SeiZleba polimerisgan (mag. polietilen- glikolis) damatebiti damcavi fena gauketdes. RruSi magnituri nanonawilakebis motavsebit micela SeiZleba garedan modebuli magnituri velit vmartot. Tu micelas fluorescirebad molekulas mivabamt (mag. Acocxal organizmtan Tavsebad nilosis lurjs), masin micelis traeqtoriasac davakvirdebit. 220

221 aqve SevniSnavT, rom SedarebiT dabali kvanturi gamosavliani fluorescencia merocianinul formasac axasiatebs. sasurvel adgilas misul micelas ui dasxivebit, anu SekumSviT davclit SigTavsisgan, garsi ki bunebrivi gzit datovebs organizms. spiropiranis orfotoniani STanTqmis marali koeficientis gamo mavne ui dasxiveba SeiZleba ori xiluli sxivis fokusirebit SevcvaloT. garda zemot arwerilisa avtorebis mier damusavebulia wamlis targetirebulad miwodebis sruliad axali gza iseti micelebit, romelic warmoiqmneba nemato qiralur Txevadkristalur kompoziciasi e.w. grzelradikaliani 6,8 dinitrowarmoebuli spiropiranebis gaxsnit. aseti tipis naertebsi Termodinamikuri wonasworoba Seferili formiskenaa gadaxrili da kompoziciasi nanostruqturireba trigeris garese iwyeba. warmoqmnili micelebi ui dasxivebis garesea SekumSuli. aseti nanokonteineris dacla daavadebul adgilze misvlisas xdeba xiluli an infrawiteli sinatlit, romelta SeRwevadoba organizmsi aremateba ultraiisferisas da, rac mtavaria, uvnebelia organizmistvis. Amgvarad, fotoqromuli spiropiranis aratoqsikuri micelebi, romelic warmoiqmneba qolesterul Txevadkristalur garemosi, SeiZleba cocxal organizmsi samkurnalo preparatis gadamtan nanokonteinerad iqnas gamoyenebuli. ui sinatlis zemoqmedebit SeiZleba micelis zomis cvlileba da konteineris dacla. samusao Sesrulebulia rustavelis erovnuli samecniero fondis dafinansebit (proeqti 11/12). literatura 1. Japaridze K., Devadze L., Maisuradze J., Petriashvili G., Zurabishvili Ts., Mzhavanadze I., Sepashvili N. A Novel Method of Increasing the Photosensitivity of Spiropyran-Containing Systems. Bulletin of the Georgian National Academy of Sciences, 2013; 7: Ylva Fahleson. Master thesis in Engineering Physics. Photochromic properties of a spiropyran photoswitch molecule in skin tissue models. Department of cell physics, KTH, Stockholm: Sweden: reziume spiropiranis micela - cocxal organizmsi samkurnalo preparatis gadamtani nanokonteineri devaze l., maisuraze j., petriasvili g., sefasvili n., zurabisvili c., mjavanaze i., axobaze S. saqartvelos teqnikuri universiteti, v.wavwanizis sax. kibernetikis instituti, saqartvelo ganxilulia avtorebis mier mikvleuli fotoqromuli spiropiranit dopirebuli nemato-qiraluri Txevadkristaluri kompoziciis nanonawilakebad _ micelebad TviTstruqturirebis movlenis gamoyeneba wamlis gadatanis saqmesi. aratoqsikuri spiropiranis sferuli micelis warmomqmneli molekulebi amfifiluria cviterionuri TaviT da arapolaruli kudit. hidrofoburi wamlit datvirtuli micela gadaadgildeba sisxlis sasualebit. samizne adgilze misuli micela ultraiisferi sinatlit dasxivebisas ikumseba da icleba. garsi bunebrivi gzit tovebs organizms. samusao dafinansebulia SoTa rustavelis erovnuli samecniero fondis mier. proeqti 11/

222 SUMMARY SPIROPYRAN'S MICELLE NANOCONTEINER DELIVERING DRAG IN LIVING ORGANISM Devadze L., Maisuradze J., Petriashvili G., Sepashvili N., Zurabishvili Ts., Mzhavanadze I., Akhobadze Sh. saqartvelos teqnikuri universiteti, v.wavwanizis sax. kibernetikis instituti, saqartvelo Photochromic spiropyran doped nemato-chiralic liquidcrystallic compositions self-structuring as nanoparticles - micells, useful for targeting drug delivery founded by the authors is discussed. Nontoxic spiropyran's spherical micella is formed by amphiphilic molecules with zwitterionic head and nonpolar tail. Loaded by hidrophobic drug, micella is moved by blood. Micella is unloaded shrank by UV irradiation, entered in the targeted place. The coat leaves the organism naturally. saqartvelosi dedata da bavsvta janmrtelobis ZiriTadi maxasiateblebisa da servisebis Sefaseba zarnaze i., zarnaze S.,Ekitovani d., lomtaze l., yajrisvili m., yufaraze m. Tbilisis saxelmwifo samedicino universiteti, sazogadoebrivi janmrtelobis departamenti, saqartvelo saqartvelos jandacvis sistemasi dedata da bavsvta janmrteloba ertert prioritets warmoadgens. jandacvis sistemis reformirebis procesma garkveuli cvlilebebi Seitana, rogorc ZiriTadi maxasiateblebis struqturasi, aseve samedicino daxmarebis raodenobasa da xarisxsi. dedata da bavsvta janmrtelobis ZiriTadi maxasiateblebisa da miwodebuli samedicino servisebis Sefaseba SesaZlebelia, rogorc oficialuri informaciis, registrirebuli monacemebis safuzvelze aseve mosaxleobis dakmayofilebis xarisxis SefasebiT. warmodgenili statia oficialur informaciaze dayrdnobit gvazlevs sasualebas mecnierulad dasabutebuli analizis safuzvelze SemuSavebuli iqnas qmediti da efeqturi RonisZiebebi misawodebeli servisebis xarisxis da janmrtelobis macveneblebis gasaumjobeseblad. kvlevis mizani: arwerilobiti kvlevis safuzvelze oficialuri informaciis analizit saqartvelosi dedata da bavsvta janmrtelobis ZiriTadi maxasiateblebisa da servisebis Sefaseba. kvlevis masala da metodebi. gamoyenebuli iqna eqspertuli analizis metodi da arwerilobiti kvleva. kvlevis Sedegebi da gansja. dedata da bavsvta janmrtelobasi ertert seriozul problemas warmoadgens sameano-ginekologiuri servisebis drouli da xarisxiani miwodeba. magalitad, cxrilsi warmodgenilia orsulta metvalyureobis maxasiateblebi qalta konsultaciasi. 222

223 cxrili 1. orsulta metvalyureobis maxasiateblebi qalta konsultaciasi metvalyureob orsuloba miitana bolomde 4 antenataluri vizitit mocva idan moixsna raoden raoden % oba oba % afxazeti awara Tbilisi kaxeti imereti samegrelo da zemo svaneti Sida qartli qvemo qartli guria samcxe - javaxeti mcxeta - mtianeti rawa - lecxumi da qvemo svaneti saqartvelo sakeisro kvetebis macvenebelis dinamika gvicvenebs, rom zrda mnisvnelovania es tendencia mxolod saqartvelosi ar fiqsirdeba, es problema dres mraval wamyvan qveyanas aqvs diagrama 1. sakeisro kvetebis dinamika saqartvelo

224 diagrama 2. sakeisro kvetis macveneblebi evropis regionsi ertwlamde asakis bavsvta sikvdilianobis dinamika gvicvenebs,rom macvenebeli mnisvnelovnad mcirdeba, rac miutitebs gaumjobesebul servisze. diagrama 3. 1 wlamde asakis bavsvta sikvdilianoba dst-sa da saqartvelosi w. avadobis struqturasi axali SemTxvevebis sixsiris analizis safuzvelze SeiZleba dadgenili iqnas, rom maralia perinatalur periodsi jamrtelobis efeqtebis xvedriti wili. 224

225 ,6 86 8, , პერინატალურ პერიოდში წარმოქმნილი ცალკეული მდგომარეობები თანდაყოლილი ანომალიები ახალშობილთა სხვა დავადებები diagrama 4. avadobis struqturasi axali SemTxvevebis sixsiris analizi amrigad, dedata da bavsvta janmrtelobasi mnisvnelovani adgili unda daetmos msoblebis informirebulobisa da janmrtelobis xelsewyobiti RonisZiebebis SemuSavebasa da ganxorcielebas. literatura 1. WHO World Health Statistics: World Health Organization. Geneva: WHO; Jamieson D, Bremen J, Measham A, et al. Disease Control Priorities in Developing Countries. Oxford: Oxford University Press; Scott B, Curtis V, Rabie T. Protecting children from diarrhoea and acute respiratory infections: the role of handwashing promotion in water and sanitation programmes. WHO Reg Health Forum. 2003;7: Gollwitzer PM, Sheeran P. Implementation intentions and goal achievement: a meta-analysis of effects and processes. Adv Exp Soc Psychol. 2006;38: Kanki B, Curtis V, Mertens T, et al. Measuring hygiene behaviours: experiences of a comprehensive approach in Burkina Faso. In: Cairncross A, Kochar V, editors. Studying 6. Hygiene Behaviour: Issues and Experiences. London: Sage Publications; Little H., Eager D. Risk, challenge and safety: Implications for play quality and playground design. Eur. Early Child Educ. Res. J. 2010;18: saqalaqo transportis sferosi dasaqmebulta Sromis pirobebis da janmrtelobis mdgomareobis kvlevis Tanamedrove mdgomareoba kverencxilaze r., cimakurize marina, xunasvili n., baqraze l., cimakurize maia., kverencxilaze g. Tbilisis saxelmwifo samedicino universitetis garemos janmrtelobisa da profesiuli medicinis mimartuleba, Tbilisi, saqartvelo dasaqmebuli mosaxleobis janmrtelobis dacva, profesiuli da profesiit ganpirobebuli daavadebebis ganvitarebis profilaqtika Sromis medicinis aqtualuri problemaa. misi regulaciis samartlebrivi safuzvelia Sesabamisi kanonqvemdebare sanitarul-higienuri aqti [3]. Sromis racionaluri pirobebis uzrunvelyofa musakta janmrtelobis mdgomareobis ganmtkicebisa da musaobisunarianobis amarlebis ZiriTadi mimartulebaa [1,2]. 225

226 erovnuli meurneobis wamyvan dargebsi mirweulma samecniero-teqnikurma progresma da gamajansarebel RonisZiebaTa kompleqsebis fartod danergvam mnisvnelovnad Seuwyo xeli dasaqmebuli mosaxleobis Sromis pirobebis da, Sesabamisad, janmrtelobis mdgomareobis gaumjobesebas. Tanamedrove profpatologiur klinikasi isviatad gvxvdeba profesiuli daavadebebisa da intoqsikaciebis klasikuri mzime formebi. amastan, sul ufro xsirdeba iseti daavadebebi, romelta ganvitareba SedarebiT naklebi intensiurobis profesiuli faqtorebis kompleqsis moqmedebas ukavsirdeba da xasiatdeba organizmis biologiuri aqtiurobis daqveitebit, adaptaciis meqanizmebis koordinaciis darrvevit [16,17]. sawarmoo garemos aradamakmayofilebeli parametrebisa da Sromis procesis mavne faqtorebis xangrzlivi da mravaljeradi moqmedeba, gancalkevebulad Tu kompleqssi, iwvevs organizmis adaptaciuri meqanizmebis gadazabvas, mis darrvevas, cvlis organizmis mraval homeostazur parametrebs, ganapirobebs organizmis aqtiurobisa da Sromis mwarmoeblurobis daqveitebas, nozologiiswina mdgomareobisa da patologiuri procesis ganvitarebas, saerto avadobis zrdas, profesiuli daavadebis ganvitarebas. sawarmoo faqtorta moqmedebis kompleqsuri xasiatis gamo, dasaqmebuli mosaxleobis Sromisa da janmrtelobis dacvis RonisZiebaTa sistemasi sul ufro mnisvnelovania janmrtelobaze moqmed faqtorta kompleqsuri Sefaseba, rac momusaveta Sromisunarianobis gazrdis, aqtiuri SromiTi saqmianobis periodisa da jansari sicocxlis gaxangrzlivebis, janmrtelobis mdgomareobis gaumjobesebisaken mimartuli RonisZiebebis SemuSavebis safuzvelia. es ki, TavisTavad, umnisvnelovanesi samedicino, socialuri da ekonomikuri problemaa. saqartvelos pirobebsi Sromis medicinis qartveli specialistebis mier mnisvnelovani da Sromatevadi samusaoebia Catarebuli erovnuli meurneobis sxvadasxva dargsi. amastan ertad, naklebadaa Seswavlili mosaxleobis dasaqmebis iseti mnisvnelovani sfero, rogoricaa Sidasaqalaqo transportis eqspluatacia. Tanamedrove msxvil qalaqebsi, mat Soris TbilisSi, Sidasaqalaqo transportis wamyvani saxea metropoliteni. 150-wliani eqspluataciis gamocdilebis miuxedavad, specialur literaturasi metad mwiri monacemebia metropolitenis musakta Sromis medicinis problemebze. arsebul erteul SromebSi ZiriTadad metropolitenis teqnikuri, ekonomikuri, zogad-sanitaruli sakitxebi da arqiteqturuli problemebia ganxiluli. Tbilisis metropolitensi, misi arsebobis TiTqmis naxevarsaukunovani istoriis manzilze, Sromis medicinis TvalsazrisiT, calkeuli kvlevebi Catarda gasuli saukunis 70-ian wlebsi, ris safuzvelzec gaanalizebuli iyo ZiriTadad Ramis cvlasi momusaveta Sromis pirobebisa da janmrtelobis mdgomareobis zogierti aspeqti, agretve memanqaneta organizmis fsiqofiziologiuri funqciis zogierti macvenebeli. kvlevis Sedegad dadginda Seswavlili kontingentis Sromis araxelsayreli rejimis arseboba, rac gavlenas axdens momusaveta organizmis funqciebisa da janmrtelobis mdgomareobaze. calkeuli kvlevebit dadgenilia Tbilisis metropolitenis garemos zogierti riskfaqtoris gavlena aq dasaqmebulta janmrtelobis mdgomareobaze; dasabutebulia kompleqsuri higienuri da klinikuri kvlevebis Catarebis aucilebloba samusao garemos da janmrtelobis mdgomareobis gaumjobesebis, samedicino momsaxurebis sistemis Semdgomi srulyofis TvalsazrisiT [15]. specialur literaturasi arsebuli SedarebiT mcire moculobis informaciis safuzvelze SegviZlia davaskvnat, rom metropolitenis musakta Sromis pirobebi xasiatdeba araxelsayrel faqtorta kompleqsit, ris Sedegadac SesaZlebelia janmrtelobis mteli rigi darrvevebis ganvitareba. 226

227 arsebuli kvlevis analizi gvicvenebs, rom metropolitenis musakta Sroma dakavsirebulia sawarmoo garemosa da Sromis procesis mteli rigi araxelsayreli faqtorეbis generaciastan, rac potenciuri riskis faqtoria mati janmrtelobisatvis. metropolitenis zogierti profesiis musakta Sromis pirobebi, garkveuli pirobitobit, SegviZlia ganvixilot rkinigzis transportis musakta Sromis pirobebtan garkveul korelaciasi. dadgenilia, rom rkinigzis transportis musakta Sroma xasiatdeba araxelsayrel faqtorta kompleqsit. sarkinigzo transportis ZiriTadi profesiebis musakta Sroma mimdinareobs araxelsayrel sawarmoo pirobebsi, rasac Tan axlavs sxvadasxva bunebisa da intensiurobis mavne da sasisi sawarmoo faqtorebis kompleqsuri moqmedeba. mavne Sromis pirobebsi uxdeba profesiuli saqmianoba dargis musakta daaxloebit 73%-s [7,9,11]. teqnikuri arwurvilobisa da mozravi Semadgenlobis eqspluatacias, saremonto da sagzao samusoebis warmoebas Tan axlavs intensiuri mtverwarmoqmna, sxvadasxva qimiuri nivtierebebis gamoyofa, intensiuri xmaurisa da vibraciis generireba, mnisvnelovani fizikuri da fsiqoemociuri datvirtva, mikroklimatisa da mikrobiologiuri dabinzurebis arasasurveli zemoqmedeba. yvela es garemoeba ganapirobebs profesiuli riskis arsebobas da rkinigzelta Soris profesiuli daavadebebis ganvitrebas. gansakutrebul yuradrebas iqcevs sarkinigzo transportis salokomotivo brigadis musakta Sromis pirobebi [6,12,13]. memanqaneebisa da mati TanaSemweebis mnisvnelovani nervul-emociuri gadazabvis gamo, SesaZlebelia arsebiti xasiatis samedicinoekonomikuri xasiatis Sedegebis ganvitareba. es garemoeba ganapirobebs mati janmrtelobis mdgomareobis specifikuri xasiatis formirebas. kerzod, Sromis procesis faqtorebidan yuradrebas iqcevs inteleqtualuri, sensoruli da emociuri datvirtvebi, musaobis rejimi. am faqtorebis arseboba ganapirobebs hipertonuli daavadebis ganvitarebas, ris gamoc memanqaneta 32% dispanserul arricxvazea. profesiul faqtorta kompleqssi wamyvania fizikuri faqtorebis (xmauris da vibraciis) generacia. Sesabamisad, mati janmrtelobis mdgomareobis macveneblebidan gansakutrebulad xsiria profesiuli daavadebebis, ZiriTadad, nervuli sistemis da neirosensoruli siyruis, ganvitareba [8,10]. ukanasknel wlebsi Cvens mier Tbilisis metropolitenis bazaze Catarebuli kvlevebis safuzvelze dadgenilia sawarmoo garemos faqtorebis formirebis kanonzomierebebi da dadgenilia momusaveta janmrtelobaze gavlenis efeqtebi. kerzod, dadginda, rom obieqtis sawarmoo garemo xasiatdeba profesiul faqtorta kompleqsit, romeltagan wamyvania xmauri da vibracia (Sromis pirobebis mavneobis 3.4. klasi). mnisvnelovania, agretve, mtvris faqtori _ mavneobis 3.2 klasi. janmrtelobis mdgomareobis efeqtebidan yuradrebas iqcevs nervuli da sisxlis mimoqcevis sistemebis daavadebebi _ 51,7 da 41,4 SemTxveva 100 gasinjulze [4,5,14]. Tumca, Cvens mier Catarebuli kompleqsuri kvlevebi askarad arasakmarisia problemis srulad gadawrisatvis. zemotqmulidan natelia, rom sarkinigzo transportis da, Sesabamisad, metropolitenis musakta Sromisa da janmrtelobis dacvis uzrunvelyofa moitxovs mati Sromis pirobebis kompleqsur Seswavlasa da Sefasebas, janmrtelobis dacvis RonisZiebaTa srulyofas, profesiuli mavneobebis zemoqmedebis Semcirebisa da, Sesabamisad, daavadebebis ganvitarebis profilaqtikis RonisZiebebis SemuSavebis sistemis Semdgom srulyofas. 227

228 literatura 1. kverencxilaze r., saakaze v., cimakurize m., baqraze l. saqartvelosi Sromis medicinis ganvitarebis ZiriTadi mimartulebebi Tanamedrove etapze.//profilaqtikuri medicina XXI saukunesi./saqartvelos profilaqtikuri medicinis mecnierebata academia. samecniero SromaTa krebuli. t. III. Tbilisi: 2006; saqartvelos kanoni `sazogadoebrivi janmrtelobis~ Sesaxeb. damtkicebulia saqartvelos prezidentis 2007 wlis 22 ivnisis #5049-Is brzanebit. saqartvelos sakanonmdeblo macne 2007; nawili I: calkeul profesiata, saqmianobis uflebata da nebartvata misarebad moqalaqeta janmrtelobis mdgomareobis Semowmebis wesi. saqartvelos Sromis, janmrtelobisa da socialuri dacvis ministris brzaneba #26/n, saqartvelos sakanonmdeblo macne 2006; nawili III: xunasvili n. Tbilisis metropolitenis sawarmoo garemos haeris dabinzurebis higienuri Sefaseba. eqsperimentuli da klinikuri medicina 2010; 2(57): xunasvili n., kverencxilaze r., cimakurize m., baqraze l., Tbilisis metropolitenis garemos fizikuri faqtorebis mdgomareoba. eqsperimentuli da klinikuri medicina 2010; 4(59): Вильк М.Ф., Капцов В.А., Панкова В.Б. Профессиональный риск работников железнодорожного транспорта. М.: РЕИНФОР: 2008; Каськов Ю.Н. Гигиеническое обоснование риска развития профессиональных заболеваний у работников железнодорожного транспорта (на примере работников локомотивных бригад). Автореф. дисс.... канд. мед. наук. М.: 2006; Копейкин Н.Ф., Станкевич А.И., Бондарева А.Р., Боева И.А. Гипертоническая болезнь как профзаболевание работников локомотивных бригад. Гигиена и санитария 2011; 3: Молодцова Е.В. Совершенствование организации профилактической помощи и восстановительного лечения пациентов с дегенеративными заболеваниями суставов. Автореф. дисс... канд. мед. наук. М.: 2010; Молодцова Е.В., Шеметова Г.Н. Актуальные и нерешенные проблемы организации лечебнопрофилактической помощи в условиях железнодорожной медицины. Саратовский научно-медицинский журнал 2010; 1: Тонкова Е.А. Гипертоническая болезнь у работников локомотивных бригад железнодорожного транспорта: факторы риска, особенности течения и основных показателей функционального состояния сердечно-сосудистой системы, их прогностическая значимость. Автореф. дисс... канд. мед. наук. М.: 2006; Хелимская И.В. Совершенствование системы оказания медицинской помощи работникам желенодорожного транспорта с хроническими заболеваниями легких. Автореф. дисс... канд. мед. наук. М.: 2012; Хелимская И.В., Капитоненко Н.А. Анализ медико-социальных факторов низкой выявляемости соматической патологии у работников Дальневосточной железной дороги. Вестник общественного здоровья и здравоохранения Дальнего Востока России. 2011; 1: Хунашвили Н.Г., Цимакуридзе М.П., Кверенчхиладзе Р.Г., Цимакуридзе Майя П., Бакрадзе Л.Ш. Особенности состояния здоровья работников Тбилисского метрополитена с учётом современных производственных и социально-экономическиых условий в Грузии. Georgian Medical News 2012; 2(203): Цимакуридзе М.П., Бакрадзе Л.Ш., Кверенчхиладзе Р.Г., Кварцхава М.Л., Майсурадзе Э.А. Принципы охраны труда и здоровья работников Тбилисского метрополитена в условиях новых социальноэкономических отношений. Georgian Medical News 2006; 4(133): Цфасман А.З. Курс железнодорожной медицины. М.: Репроцентр; 2009: Matheson M.C., Benke G., Raven J. et al. Biological dust exposure in the workplace is a risk factor for chronic obstructiv pulmanary disiseas. Torax 2005; 60(80: 645. reziume saqalaqo transportis sferosi dasaqmebulta Sromis pirobebis da janmrtelobis mdgomareobis kvlevis Tanamedrove mdgomareoba 228

229 kverencxilaze r., cimakurize marina, xunasvili n., baqraze l., cimakurize maia., kverencxilaze g. Tbilisis saxelmwifo samedicino universitetis garemos janmrtelobisa da profesiuli medicinis mimartuleba, Tbilisi, saqartvelo asaqmebuli mosaxleobis janmrtelobis dacva, profesiuli da profesiit ganpirobebuli daavadebebis ganvitarebis profilaqtika Sromis medicinis aqtualuri problemaa. aradamakmayofilebeli parametrebis sawarmoo garemosa da Sromis procesis faqtorebis xangrzlivi da mravaljeradi zemoqmedeba, gancalkevebulad Tu kompleqssi, iwvevs organizmis adaptaciuri meqanizmebs gadazabvas, mis darrvevas, cvlis organizmis mraval homeostazur parametrebs, ganapirobebs organizmis aqtiurobisa da Sromis mwarmoeblurobis daqveitebas, nozologiiswina mdgomareobisa da patologiuri procesis ganvitarebas, saerto avadobis zrdas, profesiuli daavadebis ganvitarebas. teqnikuri arwurvilobisa da mozravi Semadgenlobis eqspluatacias, saremonto da sagzao samusoebis warmoebas Tan axlavs intensiuri mtverwarmoqmna, sxvadasxva qimiuri nivtierebebis gamoyofa, intensiuri xmaurisa da vibraciis generireba, mnisvnelovani fizikuri da fsiqoemociuri datvirtva, mikroklimatisa da mikrobiologiuri dabinzurebis arasasurveli zemoqmedeba. yvela es garemoeba ganapirobebs profesiuli riskis arsebobas da profesiuli daavadebebis ganvitarebis albatobis zrdas. SUMMARY MODERN STATE OF RESEARCH WORKS ABOUT LABOR CONDITIONS AND HEALTH STATE OF THE EMPLOYEES IN THE SPHERE OF CITY TRANSPORT Kverenchxiladze R., Cimakuridze Marina, Khunashvili N., Baqradze L., Cimakuridze Maia, Kverenchxiladze G Tbilisi State Medical University, Department of Environment, Health and Professional Medicine, Tbilisi, Georgia Healthcare of employed population, prophylactic of diseases development conditioned by professional point of view, is the actual problem of labour medicine. Long termed and multiple influence of the factors of enterprise environment and labour process of non-satisfactory parameters, separately or in complex, causes surging adaptive mechanisms of human body, its violation, changes many homeostasic parameters, conditions activity of human body and descends its working productivity, prenosology condition and development of pathologic process, increasing common diseases, development of professional disease. Technologic equipment and rolling stock maintenance, production of repairing and road works are accompanied with intensive dust appearance, emissions of differrent chemical substances, generating intensive noise and vibration, significant physical and psycho-emotional loading, non-willing influence of microbiologic and microclimate pollution. All these circumstances are conditioned by existance of professional risk and increasing probability of professional diseases development. 229

230 BIOLOGICAL CHARACTERS OF ASTRAGALUS GLYCYPHYLLUS UNDER CONDITIONS OF INTRODUCTION 1 Lysiuk R., 2 Skibitska M. 1 Department of Pharmacognosy and Botany, Danylo Halytsky Lviv National Medical University, 69, Pekarska str., 79010, Lviv, Ukraine; 2 Botanical Garden of Ivan Franko National University of Lviv, 44, Cheremshyny, 79014, Lviv, Ukraine Chronic renal failure due to gradual destruction of sufficient nephrons represents a massive problem in the developed world. Diabetic nephropathy is the major culprit. Botanical medicine has much to offer not only to help forestall the need for dialysis by treating the causes and effects of renal failure, but also to reduce the many adverse effects of dialysis itself [1]. Leaves and flowers of Astragalus falcatus are used for obtaining the individual flavone glycoside flaronin (robinin) of hypoazotemic activity. The medicine is successfully applied to treat chronic renal insufficiency caused by pyelonephritis and other kidney diseases [2]. Astragalus glycyphyllus L., Fabaceae family, contains robinin [3]. Among the important tasks currently may be considered an investigation of robinin-yielding and other plants of hypoazotemic activity with sufficient resource stocks in Ukraine, therefore, Astragalus glycyphyllus L. becomes the object of a particular interest. Astragalus glycyphyllus is a perennial, bare, stems cm long, procumbent up to creeping, ascendent, angular, glabrous plant. Seeds reniform or asymmetric cordiform, flattish, hilum sunken, rounded with a narrow white hem; surface egg-yellow to yellowish or pale-brown. Native to most of Europe, mainly in mountains in the south, in forests, shrubberies, embankments [4]. Its leaves are used as substitute for tea. A. glycyphyllos contains sterols and triterpenoid sapogenins, mainly of the cycloartane skeleton. The large variety of flavone and flavonol glycosides (these latter are the most abundant) occurs in Astragalus spp. [5]. The flavonoid portion of A. glycyphyllos is exemplified by apigenin, kaemferol and their glycosides, quercitin, isorhamnetin [3]. The objective of the work comprises analysis of own results concerning introduction of Astragalus glycyphyllus in the Botanical Garden of Ivan Franko National University of Lviv, Ukraine. The plant was introduced in 1998 from the seeds. The primary seed material for introduction was collected in wild in lower mountainous range of the Carpathians. No growth stimulants, fertilizers, additional irrigation were applied within multi-year cultivation experiments. Under outdoor introduction conditions in the Botanical Garden, vegetation of the species begins in the third ten day period of March - the first ten day period of April. The budding period occurs during May-June. The blossoming is observed in the first - second ten day periods of June, becoming abundant in July and August. The fruiting period may last from June till September, and vegetation of not damaged samples till the first frozen (the end of November). The frost injuries of the investigated species were not observed. The corm length varies from 0,5 to 1,2 m, occasionally up to 1,5 m. Fruit a legume, 2.0 3,5 cm in length. Laboratory germination rate of freshly collected Astragalus glycyphyllus seeds (waxed maturity) is 46,8 %. Soil germination of the stratified seeds is 80,2%, and laboratory germination of scarified seeds after stratification 60,4%. The plant propagates from seeds and vegetatively. 230

231 Considering the complex estimation for successfulness of the plant introduction, Astragalus glycyphyllos is a promising species for cultivation in conditions of Lviv region, Western part of Ukraine, for further application with medicinal purposes. REFERENCES 1. Yarnell E., Abascal K., Rountree R. Clinical Botanical Medicine. 2 nd edn. New Rochelle: Mary Ann Liebert, Inc.: 2003; Kemertelidze E.P. Biologically Active Compounds and Medical Preparations from Some Plants Growing in Georgia. Chemistry for Sustainable Development 2008; 16: Kovalyova A.M. Flavonoids of Genus Astragalus L. Plants in the Flora of the C.I.S. Countries Visnyk Farmaciyi, 1998; 1(17): (in Ukrainian). 4. Bojˇnansky V., Fargašova Ag. Atlas of Seeds and Fruits of Central and East-European Flora. The Carpathian Mountains Region. Springer: 2007; Pistelli L. Secondary Metabolites of Genus Astragalus: Structure and Biological Activity. In: Studies in Natural Products Chemistry, 27, Atta-Ur-Rahman (Ed.). Elsevier Science B.V.: 2002; perilas miwiszeda nawilebsi rozmarinis mjavas raodenobrivi Semcvelobis gansazrvra maralefeqturi sitxuri qromatografiiis da qromatomasspeqtrometruli metodebit SaSiaSvili n., joxaze m., kuwuxize j., bakurize a., berasvili d. Tbilisis saxelmwifo samedicino universiteti, farmakognoziis da botanikis departamenti, saqartvelo perilas fotlebi popularuli sakvebia iaponiis, CineTisa da aziis sxva qveynebsi. kvlevebit dadgenilia perilas damtrgunveli efeqti dabali simkvrivis lipoproteidebis Jangvis unarze in vitro da in vivo cdebsi. perilas saxeobebis antioqsidanturi aqtiuroba ganpirobebulia polifenoluri naertebit. antocianidebis, luteolinis, apigeninis, skutelarinis, kofeinis da rozmarinis mjavis aqtivobis Seswavlisas dadginda, rom CamoTvlili naertebidan mnisvnelovan antioqsidantur moqmedebas avlens rozmarinis mjava. misi antioqsidanturi aqtiuroba aremateba E da C vitaminis aqtiurobas [1,2]. perila, rogorc samedicino danisnulebis samkurnalo mcenare, arwerilia alergiuli daavadebebis, mat Soris bronquli astmis dros. gamokvlevebit in vivo cdasi dadgenilia, rom perilas monaxarss da mis Semadgenel komponentebs gansakutrebit ki rozmarinis mjavas gaacnia antialergiuli da antebis sawinaarmdego moqmedeba [3,4]. literaturis mimoxilvis da sakutari kvlevebis safuzvelze dadginda rom perilas SemadgenlobaSi Semaval biologiurad aqtiur nivtierebata Soris antioqsidanturi da antialergiuli moqmedebis TvalsazrisiT mnisvnelovania rozmarinis mjava. kvlevis mizans Seadgenda: saqartvelosi gavrcelebul perilas miwiszeda nawilebsi rozmarinis mjavas raodenobiti Semcvelobis gansazrvra maralefeqturi sitxuri qromatografiis metodit. kvlevis obieqti: kvlevis obieqts warmoadgenda Coxaturis raionis, sofel xidistavsi perilas miwiszeda nawilebi. Segrovili 231

232 kvlevis metodebi: qromatografirebas vatarebdit maralefeqtur sitxur qromatografze, romelic arwurvili iyo vakuum degazerit, binaruli tumboti, fotodiod deteqtorit (DAD) Semdeg pirobebsi: qromatografi: AGILENT TECHNOLOGIES 1290 Infinity AGILENT TECHNOLOGIES 6460 Triple quad LC/MS, sveti, stacionaruli faza: Zorbax Eclipse plus C18 (100 X 2.1 mm, 1.8 mkm) winasveti: UHPLC GUARD Zorbax Eclipse plus C18 (5 X 2.1 mm, 1.8 mkm) svetis temperatura: 40 0 C mozravi faza: 0.02 M amoniumis formiati-acetonitrili (40:60), ph miyvanili 3-mde WianWvelmJaviT. rejimi: izokratuli sinjis moculoba: 5.0 mkl mozravi fazis sicqare: 0.5 ml/wt skanirebis rejimi - MRM, TIC DAD: 254 nm MRM rejimsi rozmarinis mjavas deteqtirebis optimaluri parametrebia: fragmentor energia =120 koloziis energia =15 prekursor ioni [M+H] - =359 produqt ioni [M+H] - =161 kvlevis Sedegebis ganxilva. vinaidan mcenareuli nedleuli Seicavs biologiurad aqtiur nivtierebata kompleqss, individualuri nivtierebis raodenobiti gansazrvrisas gansakutrebit mnisvnelovania eqstraqciis optimaluri pirobebis dadgena, rata ganxorcieldes nedleulis maqsimaluri eqstragireba. mcenaris eqtraqtebi winaswar momzadebuli iyo ultrabgerit abazanaze, sxvadasxva gamxsnelis gamoyenebit, gansxvavebuli eqtraqciis pirobebsi. eqsperimentuli kvlevebit dadginda optimaluri eqstragenti, nedleuli/gamxsnelis Tanafardoba, eqtragirebis dro, jeradoba da temperatura eqtraqciis optimaluri pirobis SerCevis GSedegebi moyvanilia NcxrilSi. cxrili 1. rozmarinis mjavas Semcveloba perilas miwiszeda nawilebidan momzadebul eqstraqtebsi N gamxsneli nedleuli/g amxsnelis Tanafardob a jeradob a 232 eqstraqcii s dro temperatur a koncentrac ia mg/g 1 wyali 1: O C metanoli 1: O C etanoli 40% 1: O C etanoli 70% 1: O C etanoli 96% 1: O C etanoli 70% 1: O C 25.71

233 etanoli 70% etanoli 70% etanoli 70% etanoli 70% etanoli 70% etanoli 70% etanoli 70% etanoli 70% 1: O C : O C : O C : O C : O C : O C : otaxis temperatur a : O C rogorc cxrilis monacemebidan Cans, 70%-iani etilis spirtit, nedleulisa da eqstragentis 1:10-Tan TanafardobiT, otaxis temperaturaze orjerdi eqstrqciit (30 wt da 15wT) miirweva perilas miwiszeda nawilebidan rozmarinis mjavas maqsimaluri gamowvlilva. rozmarinis mjavas standartuli nimusisa da sakvlevi obieqtis sitxuri qromatografirebis Sedegebi moyvanilia NsuraTebze 1, 2 da 3. sur. 1. rozmarinis mjavas standartuli nimusis sitxuri qromatograma sur. 2. perilas eqstraqtis sitxuri qromatograma 233

234 sur. 3. rozmarinis mjavas da perilas sitxovani eqstraqtis MS/MS qromatogramebi daskvnebi 1. maralefeqturi sitxuri qromatografiis metodit dadginda perilas miwiszeda nawilebidan rozmarinis mjavas eqtragirebis optimaluri pirobebi: eqstragenti 70 % etilis spirti, nedleuli/ eqstragentis Tanafardoba 1:10, orjeradi eqstraqcia otaxis temperaturaze (dro 30 wt da 15 wt); 2. SemuSavda rozmarinis mjavas TvisebiT-raodenobiTi gansazrvris metodika maralefeqturi sitxuri qromatografiis da qromatomasspeqtrometruli metodis gamoyenebit; 3. perilas miwiszeda nawilebsi rozmarinis mjavas raodenobiti Semcveloba Seadgens 29 mg/g. literatura 1. Gulcin I, Berashvili D, Gepdiremen A. Antiradical and antioxidant activity of total anthocyanins from Perilla pankinensis decne. J Ethnopharmacol 2005;101(1-3): Linghua Meng, Yves F. Lozano, Emile M. Gaydou and Bin Li Antioxidant Activities of Polyphenols Extracted from Perilla frutescens Varieties. Molecules 2009; 14: Makino T., Furuta Y., Wakushima H., Fujii H., Saito K., Kano Y. Anti-allergic effect of Perillafrutescens and its active constituents. Phytother. Res. 2003; 17: Naomi Osakabe, Akiko Yasuda, Midori Natsume, Toshikazu Yoshikawa. Rosmarinic acid inhibits epidermal inflammatory responses: anticarcinogenic effect of Perilla frutescens extract in the murine two-stage skin model. Carcinogenesis 2004; 25(4): reziume perilas miwiszeda nawilebsi rozmarinis mjavas raodenobrivi Semcvelobis gansazrvra maralefeqturi sitxuri qromatografiiis da qromatomasspeqtrometruli metodebit SaSiaSvili n., joxaze m., kuwuxize j., bakurize a., berasvili d. Tbilisis saxelmwifo samedicino universiteti, farmakognoziis da botanikis departamenti, saqartvelo literaturis mimoxilvis da sakutari kvlevebis safuzvelze dadginda rom perilas SemadgenlobaSi Semaval biologiurad aqtiur nivtierebata Soris antioqsidanturi, 234

235 antebis sawinaarmdego da antialergiuli moqmedebis TvalsazrisiT mnisvnelovania rozmarinis mjava. kvlevis mizans Seadgenda: saqartvelosi gavrcelebul perilas miwiszeda nawilebsi rozmarinis mjavas raodenobiti Semcvelobis gansazrvra maralefeqturi sitxuri qromatografiis da qromatomasspeqtrometruli metodebit. eqsperimentis Sedegad dadginda perilas miwiszeda nawilebidan rozmarinis mjavas eqtragirebis optimaluri pirobebi: eqstragenti 70 % etilis spirti, nedleuli/eqstragentis Tanafardoba 1:10, orjeradi eqstraqcia otaxis temperaturaze, eqstraqciis dro 30 wt da 15 wt. SemuSavda rozmarinis mjavas raodenobiti gansazrvris metodika maralefeqturi sitxuri qromatografiis metodis gamoyenebit. perilas miwiszeda nawilebsi rozmarinis mjavas Semcveloba Seadgens 29 mg/g. SUMMARY QUANTIFICATION OF ROSMARINIC ACID IN PERILLA NANKINENSIS L. GROWING IN GEORGIA, USING HIGH- PERFOMANCE LIQUID CHROMATOGRAPY AND LIQUID CHROMATOGRAPHY MASS SPECTROMETRY Shashiashvili N, Jokhadze M., Kuchukhidze J, Bakuridze A., BeraSvili D. Tbilisi State Medical University, Department of Botany and Pharmacognosy; Faculty of Pharmacy, Georgia Based on the studies Rosmarinic acid (RA) is a one of the important compound found in Perilla. It has a number of interesting biological activities, for example anti-inflammatory and antioxidant. RA helps to prevent cell damage caused by free radicals. Perilla, rich in rosmarinic acid, is used for its anti-allergic activity. High-perfomance liquid chromatograpy (HPLC) and Liquid chromatography mass spectrometry (LC-MS/MS) method were develoed for the qualitive and quantitive determination of rosmarinic acid in the aerial parts of P. nankinensis. The process of extraction of rosmarinic acid (RA), from the of Perilla nankinensis L. is studied. The impact of some main process parameters (solvent concentration, process temperature and process duration) is experimentally determined. The general conditions for better practical extraction of RA from perilla aerial parts are defined. The concentration varied significantly according to the different condition of extraction. The highest content of rosmarinic acid (29 mg/g) was found in the aerial parts of perilla extracted twice by ethanol (70%), during 30 min and 15 min, at room temperature. The results indicated that the developed HPLC method could be used for the quality control of P. nankinensis and for the standardization of its extracts in rosmarinic acid. parodontis daavadebebis samkurnalo-profilaqtikuri firfitebis SemuSaveba cagareisvili n., kobaxize n., qurdiani n., miqaia g., wurwumia i. Tbilisis saxelmwifo samedicino universiteti, farmacevtuli teqnologiis departamenti, saqartvelo stomatologiuri profilis nozologiebs Soris parodontis daavadebebi yvelaze fartodaa gavrcelebuli. dreisatvis mowodebulia arnisnuli daavadebis profilaqtikisa da mkurnalobis mravalricxovani metodi da sasualeba. miuxedavad amisa sakmaod bevri problema jer kidev gadauwreli rceba, - piris Rrus anatomiur 235

236 fiziologiuri Taviseburebebidan gamomdinare swrafad xdeba medikamentebis Camorecxva, rac artulebs mkurnalobis process. arnisnuli problema ganapirobebs axali preparatebisa da mati racionaluri kombinaciebis mudmivi Ziebis aucileblobas [1]. am TvalsazrisiT samkurnalo firfitebis gamoyenebam xeli Seuwyo iseti Terapiuli sistemis Seqmnas, romelebic aqtiuri nivtierebis moqmedebis prolongirebis sasualebas izleva [3]. parodontis daavadebebis dros adgili aqvs qsovilsi antebiti da antebitdestruqciul procesebis mimdinareobas, mikrocirkulaciis funqcionaluri da organuli xasiatis darrvevebs agretve organizmis barieruli sistemis moslas. arnisnulidan gamomdinare, aqtiur farmacevtul ingredientebad SerCeulia or komponentiani kompozicia - TuTiahialuronis mjavas 0.2 %-iani (kuriozinis xsnari) da qlorheqsidinis biglukonatis 0.05 %-iani xsnari [2]. kuriozini warmoadgens hialuronis mjavasa da TuTiis asociats. hialuronis mjava SemaerTebeli qsovilebis SemakavSirebeli bunebrivi struqturis normalizebis xarjze acqarebs parodontis dazianebuli qsovilebis rekonstruqciis process, xolo TuTiis ionebs axasiatebt Zlieri baqteriostatikuri moqmedeba. preparati aseve xasiatdeba tkivilgamayucebeli da SeSupebis sawinaarmdego moqmedebit [5,6]. qlorheqsidini warmoadgens ert-ert yvelaze aqtiur antiseptiks, xasiatdeba baqteriostatikuri, baqteriociduli, fungiciduri da viruliciduri moqmedebebit. igi inarcunebs aqtivobas sisxlisa da Cirqovani eqsudatebis Tanaobisas [4]. zemotarnisnulidan gamomdinare parodontis samkurnalo or komponentiani aqtiuri farmacevtuli ingredientebis Semcveli firfitebis Seqmna ert-erti aqtualuri problemaa praqtikuli stomatologiisatvis. kvlevis mizans warmoadgenda parodontis daavadebebis samkurnalo-profilaqtikuri firfitebis SemuSaveba. kvlevis masala da metodebi. kvlevis obieqts warmoadgenda parodontis samkurnalo firfitebi; aqtiuri farmacevtuli ingredientebi: TuTiahialuronis mjava da qlorheqsidinis biglukonati; damxmare nivtierebebi: karboqsimetil-celulozas natriumi (Nakmc), metilceluloza (mc), natriumis alginati, polivinilpirolidoni (pvp), polivinilis spirti (pvs), Jelatini da glicerini. kvlevis Sedegebis ganxilva. samkurnalo firfitebis optimaluri Semadgenlobis SesarCevad sawyis etapze Seswavlilia apkwarmomqmneli biodegradirebadi polimerebis 20 kompozicia sxvadasxva SemadgenlobiTa da TanafardobiT. SerCevis kriteriumad gamoyenebul iyo firfitebis damakmayofilebeli garegnuli iersaxe - ertgvarovneba, matricidan kargi mocilebis unari, mikronaxetqebis ar arseboba, elastikuroba da adgeziuroba. skriningis Sedegad dadginda, rom natrikarboqsimetilcelulozas da metilcelulozas 5%-ze meti raodenobit gamoyenebis SemTxvevaSi miireba sqeli da myife firfitebi, 2%-ze naklebi raodenobit Zalian Txeli. polivinilpirolidonis da polivinilis spirtis gamoyenebisas 15%-ze naklebi raodenobit miireba webvadi, araelastikuri da Txeli firfitebi. natriumis alginatis 2%-ze naklebi raodenobit gamoye-nebisas miireba Zalian Txeli apkebi, romlebic matricidan moxsnis dros advilad kargavda mtlianobas, xolo 4%-ze meti raodenobit gamoyenebisas warmoiqmneboda mikronaxetqebi. glicerini 4%-ze meti koncentraciit warmoqmnida webvad firfitebs. 236

237 Sedegad, winaswari kvlevebis safuzvelze SerCeulia hidrofiluri bunebis polimerebis 12 kompozicia. yvela kompoziciasi plastifikators warmoadgenda antiseptikuri Tvisebis mqone glicerini 2 3% mde, ph (cxrili 1). cxrili 1. sakvlevi kompoziciebis Semadgenloba fuzeebis Semadgenloba Na kmc 3,0 glicerini_2,0 Na kmc 4,0 glicerini_2,0 mc 3,0 glicerini_2,0 mc 4,0 glicerini_2,3 Na alginate-3,0 glicerini_2,0 Naalginati_4,0 glicerini_2,0 apkwar moqmni s unari adgezi uroba ± fuzeebis Semadgenloba mc 1,0 Jelatini_6,0 glicerini_3,0 mc 4,0 pvp_1,5 Jelatini_5,0 glicerini_3,0 pvp_2,0 pvs_4,5 glicerini_2,0 Na kmc 1,0 Na alginati_1,0 pvp_1,5 glicerini_2,0 Na kmc 3,0 pvs_4,0 glicerini_2,0 mc 2,0 Na alginati_2,0 glicerini_3,0 apkwarm oqmnis unari adgezi uroba -± ± SeniSvna: ±- arasakmarisad gamoxatuli Tviseba + gaacnia Tviseba ++ Zlier gamoxatuli Tviseba mirebuli kompoziciebidan sauketeso macveneblebit xasiatdeba polimeruli firfitebi 1, 3, 5, 11, 12, romlebic gamoyenebulia Semdgomi kvlevebisatvis. Seswavlilia SerCeuli firfitebis teqnologi-uri Tvisebebi. Sedegebi mocemulia 2 cxrilsi. cxrili 2. polimeruli firfitebis teqnologiuri maxasiateblebi Semadgenloba (%) sasualo masa, (g) sisqe (sm) gaxsni s dro, (wt) tensemcv eloba,% airgamta roba g/m 2 st meqanikuri simtkice n/m Na kmc 3,0 glicerini _ 2,0 0,786± 0,003 0,105±0, ,93±0,5 75,4 ± 2, ±1,2 2. mc 3,0 glicerini _ 2,0 0,731± 0,003 0,103±0, ,4±0,5 79,8 ± 2, ±1,2 237

238 3. mc 2,0 Naalginati _2,0 glicerini _ 3,0 4. Naalginati_3,0 glicerini _ 2,0 5. Na kmc 3,0 pvs _ 4,0 glicerini _ 2,0 0,823 ± 0,004 0,109±0, ,2±0,3 82,2±2, ±1,3 0,813 ± 0,004 0,120±0, ,7±0,4 68,8 ± 2, ±0,98 0,923± 0,004 0,132±0, ,23±0,4 61,4± 2, ±1,2 Catarebuli kvlevebis safuzvelze SerCeulia 3 kompozicia. aqtiuri farmacevtuli ingredientebis dozirebis gatvaliswinebita da SerCeuli apkwarmomqmneli kompoziciis safuzvelze mowodebulia parodontis samkurnalo firfitebis Semadgenloba (cxrili 3). cxrili 3. parodontis samkurnalo firfitebis kompoziciis Semadgenloba (%) Naalgina ti mc glicerini kuriozinis 0,2% xsnari qlorheqsidinis 0,05%-iani xsnari 2,0 2,0 3, parodontis samkurnalo firfitebis momzadebis teqnologia Sedgeba Semdegi stadiebisgan: apkwarmomqmneli masis momzadeba, aqtiuri ingredientebis Setana, deaeracia da Sroba. firfitebis standartizacia Catarda fizikuri (feri, gamwvirvaloba, firfitis zoma, forma, sasualo masa) qimiuri (xsnadoba, ph, moqmedi nivtierebebis raodenobrivi Semcveloba, Tvisobrivi analizi) da teqnologiuri (airgamtaroba, tensemcveloba, meqanikuri simtkice, gaxsnis dro) maxasiateblebis mixedvit. daskvnebi: Catarebuli eqsperimentuli kvlevebis safuzvelze SemuSavebulia parodontis daavadebebis samkurnalo-profilaqtikuri firfitebis receptura da teqnologia. Seswavlilia da dadgenilia parodontis daavadebebis samkurnalo-profilaqtikuri firfitebis ketilxarisxovnebis macveneblebi. literatura 1. x. qorize. qronikuli recidiuli afturi stomatitis riskis faqtorebis Sefaseba da mkurnalobis optimizacia. disertacia medicinis mecnierebata kandidatis samecniero xarisxis mosapoveblad Лемецкая Т.И. Этиология, патогенез, классификация заболеваний пародонта. Стоматология. Спец. выпуск 1998; Алексеева И.В., Панцуркин В.И., Триерс В.А., Тамоян Т.Н. Разработка и клиническая апробация биорастворимых лекарственных пленок для лечения стоматологических заболеваний. Рациональное использование лекарств: материалы Рос. науч.-практ. конф. (10-12 марта 2004 года), Пермь). Пермь: 2004; Сирак С.В., Лолаева А.В. Профилактика кариеса зубов и воспалительных заболеваний пародонта с использованием зубных эликсиров. Вестник медицинского стоматологического института. М.: 2011; 1: Moseley R, Waddington RJ, Embery G. Hyaluronan and its potential role in periodontal healing. Dent Update. 2002; 29(3):

239 6. Xu Y, Hofling K, Fimmers R, Frentzen M, Jervoe-Storm PM. Clinical and microbiological effects of topical subgingival application of hyaluronic acid gel adjunctive to scaling and root planing in the treatment of chronic periodontitis. J Periodontol. 2004; 75(8): reziume parodontis daavadebebis samkurnalo-profilaqtikuri firfitebis SemuSaveba cagareisvili n., kobaxize n., qurdiani n., miqaia g., wurwumia i. Tbilisis saxelmwifo samedicino universiteti, farmacevtuli teqnologiis departamenti. saqartvelo kvlevis mizans warmoadgenda stomatologiur daavadebebs Soris fartod gavrcelebuli parodontis daavadebebis samkurnalo-profilaqtikuri prolongirebuli moqmedebis firfitebis Semadgenlobisa da teqnologiis SemuSaveba. winaswari kvlevebis safuzvelze SerCeul iqna hidrofiluri bunebis polimeruli matrica-matarebeli (mc, Na alginati, glicerini 2:2:3) Semdegi teqnologiuri maxasiateblebit: sasualo masa, sisqe, gaxsnis dro, tensemcveloba, airgamtaroba, meqanikuri simtkice. imis gatvaliswinebit, rom parodontis daavadebebis dros adgili aqvs qsovilsi antebiti da antebit-destruqciul procesebis mimdinareobas, mikrocirkulaciis funqcionaluri da organuli xasiatis darrvevebs, organizmis barieruli sistemis moslas, matrica-matarebelsi moqmedi nivtierebebis saxit Setanil iqna cinkhialuronis mjavas 0,2% xsnari (kuriozinis xsnari) da qlorheqsidinis biglukonatis 0,05 % xsnari. (78:15) firfitebis standartizacia Catarda fizikuri (feri, gam-wvirvaloba, firfitis zoma, forma, sasualo masa) qimiuri (xsnadoba, ph, moqmedi nivtierebebis raodenobrivi Semcveloba, Tvisobrivi analizi) da teqnologiuri (airgamtaroba, tensemcveloba, meqanikuri simtkice, gaxsnis dro) maxasiateblebis mixedvit. SUMMARY DEVELOPMENT OF MEDICAL PLATES FOR THE TREATMENT OF PERIODONTAL DISEASES Tsagareishvili N., Kobakhidze N., Kurdiani N., Mikaia G., Tsurtsumia I. Tbilisi State Medical University, Department of Pharmaceutical Technology The purpose of the study was to develop composition and technology of therapeutic/prophylactic plates with prolonged mode of action for use in the treatment of one of the widespread dental problems - periodontal diseases. Based on preliminary studies, hydrophilic polymer carrier matrix (MC, Sodium Alginate, glycerol 2:2:3) with defined technological characteristics was selected: average weight, thickness, dissolution time, water content, airpermeability, mechanical resistance. Given that during periodontal diseases have a place inflammatory and inflammatory/destructive processes in tissues together with functional and organic disorders of microcirculation and organism barrier system disruptions, zinc hyaluronate 0.2% solution (Curiosin solution) and chlorhexidin bigluconate 0.05% solution (78:15) were incorporated into the carrier matrix as active ingredients. 239

240 Medical plates were standardized according to physical (color, clarity/transparency, dimensions, shape, average weight), chemical (solubility, ph, active ingredients identity and assay) and technological (air-permeability, water content, mechanical resistance, dissolution time) characteristics. axali antialergiuli preparati dualer-g T. WumburiZe, z. bendeliani, T. CikvilaZe, n. kvijinaze, n. sulasvili Tbilisis saxelmwifo samedicino universiteti, socialuri da klinikuri farmaciis departamenti, saqartvelo preparati dualer-g warmoadgens ori cnobili antialergiuli wamlis (qvifenadinis da seqvifenadinis) kombinacias. Ddualer-G tabletebsi orive aqtiuri komponenti toli raodenobitaa. aseti kombinaciis ert formasi gamoyeneba ganapiroba winaklinikuri kvlevis Sedegebma, romelta mixedvit, preparatebis ertdrouli moqmedebis dros arinisneba potencirebuli sinergizmi kombinirebuli preparatis efeqti samjer aremateba calcalke komponentebis efeqts imave dozebsi. preparatis aqtiuri komponentebi warmoadgenen meore Taobis antihistaminur preparatebs romlebic blokaven H 1 receptorebs ar gadian hematoencefalur bariers da ar iwveven Zilis momgvrel efeqts. isini agretve amcireben histaminis koncentracias qsovilebsi, rac dakavsirebulia mat TvisebasTan gaaqtiuron diaminoqsidaza histaminis damsleli fermenti. mat ar gaacnit antiadrenerguli da qolinoblkatoruli Tvisebebi, rac SesaZlebels xdis mis gamoyenebas im pacientebsi vistvisac ukunacvenebia antiqolinerguli Tvisebebis mqone antialergiuli preparatebis danisvna mati gverditi efeqtebis gamo (Sardis Sekaveba, mxedvelobis darrveva). kombinacias damatebit gaacnia gamoxatuli antiserotoninuli (5HHT s1 receptorebis mablokirebeli) Tvisebebi rac afartoebs preparatis antialergiuli moqmedebis speqtrs. preparatis klinikuri kvleva Catarda jandacvis saministros farmacevtuli samsaxuris mier damtkicebuli protokolis Sesabamisad 30 pacientze matgan 22-s (sakvlevi jgufi) utardeboda mkurnaloba preparatit dualer-g 8 pacienti Seadgenda Sesadarebel jgufs. monawile pacientebs arenisnebodat dermatozebi (WinWric cieba. neirodermiti, atopiuri dermatiti, Jiberis vardisferi pitiriazi, toqsodermia, witeli brtyeli liqeni, egzema, fsoriazi.) Catarebuli mkurnalobis Sedegad sakvlev jgufsi 22 pacientidan 20-s arenisneboda gamokvetili Terapiuli efeqti. rigi pacientebisa (I jgufi) romlebic adre mkurnalobdnen sxva antialergiuli preparatebit arnisnaven rom dualer-g aranakleb da zogjer ufro karg Sedegs (gansakutrebit rinitisa da qavilis mxriv) vidre sxva preparatebi, kerzod eriusi (desloratadini) WinWris ciebis dros da efeqturobit identuria parlazinis (cetirizini). arsanisnavia, rom preparatis efeqti swrafad iwyeba (15-30wT) da xangrzlivad narcundeba (12-24 saatis ganmavlobasi dozis mixedvit). pacientebi ar arnisnavdnen gverdit efeqtebs im SemTxvevebSic ki rodesac miires preparatis ertjerad rekomendirebul dozaze ornaxevarjer meti (100 mg). 240

241 kvlevis Sedegebidan gamomdinareobs, rom preparati dualer-g G axdens gamokvetil antialergiul efeqts, romelic bevrad aremateba Sesadarebeli preparatis moqmedebas, gansakutrebit WinWris ciebis, atopiuri dermatitis, eritemis, witeli brtyeli liqenis da Jiberis vardisferi pitiriazis SemTxvevebSi. NEW ANTIALLERGIC DRUG DUALLER-G Tchumburidze T., Bendeliani Z., Chikviladze T., Kvizhinadze N., Sulashvili N. Tbilisi State Medical University, Department of Social and Clinical Pharmacy, Georgia Allergic reaction plays leading role in pathogenesis of dermatosis and mechanism of such reactions are based on release of histamine and serotonin. Be course of this development of drug with both antihistamine and antiserotonine activity was the goal of this study. Drugs with close chemical structure and pharmacological activity where selected from derivates of quinuclidin carbinols. The differences in pharmacological activity of different compounds makes Dualler-G a new antiallergic drug with antihistamine and antiserotonine activity. The goal of the stydy was clinical trial of Dualler-G in patients with dermatosis. Obtained data suggest that Dualler-G shows high effectiveness in treatment of different types of dermatozis. Objective: The effect of Dualler-G (DG), an oral antiallergic drug, was evaluated in patients displaying different kinds of dermatozis (urticarea, neirodermitis, lichen ruber planus, eczema). Methods: A total of 30 patients diagnosed with dermatozis were randomized to receive in an open fashion 60 mg of DG per day, or 75 mg of quifenadine (antihistamine H-1 receptor bloker also the derivative of quinuclidine carbinol) as a drug of comparison (controls) for 2 weeks. Efficacy was assessed according to the global improvement rating (GIR) of elements on skin or itching as symptoms or signs. Results: Patients treated with DG (cases of urticarea, neirodermitis and lichen ruber planus) had superior improvements in their symptoms GIRs(elements on skin and itching ) compared to controls overall across the 2 week trial, but not in cases of eczema GIRs. However, even in cases of eczema level of eosinophils was reduced and severity of symptoms as well. Clinical course of patients treated with DG tended to be significantly better than that of patients treated with quifenadine, and the symptom GIRs were significantly correlated in the DG-treated group. Conclusion: These data suggest that DG provide direct efficacy on the symptoms (skin elements and itching) in patients with different kinds of dermatozis, and its efficacy is mach higher then that of relative drug quifenadine. leqsotanis (bromazepami) gansazrvra adamianis nerwyvsi maralefeqturi sitxovani qromatografiuli metodit kunwulia l., surgulaze T., maxaraze r., bojaze a., ioramasvili h. Tbilisis saxelmwifo samedicino universiteti, farmacevtuli da toqsikologiuri qimiis departamenti, saqartvelo leqsotani warmoadgens anqsiolizur sasualebas (Sveicariuli), romelic saqartvelos farmacevtul bazarze Semotanilia farmacevtuli firmis Roche -s mier. leqsotanis arapatenturi saxelwodebaa bromazepami. igi qimiurad benzodiazepinebis warmoebulia, 241

242 mis struqturasi bromis SeyvaniT gazlierebul iqna kruncxvis sawinaarmdego da sedaciuri efeqtebi. leqsotanis farmakokinetikuri kvlevebistvis warmatebit gamoiyeneba maralefeqturi sitxovani qromatografiuli metodebi, ultraiisferi deteqtirebit [3-5]. arsanisnavia amerikeli mecnierebis _ qristina murisa da sintia kulteris mier Catarebuli kvlevebi. 14 benzodiazepinis jgufis preparatis metabolizmisa da farmakokinetikis Seswavlis Sedegad mat mier bromazepamis 3 metaboliti iqna armocenili, romelta struqtura dadgenil iqna [6-9]. dresdreobit sakmaod problemuria stresit gamowveuli wylulebis ganvitarebis marali riskebis Semcirebis gzebis Zieba. am mxriv benzodiazepinebis gamoyeneba wylulis samkurnalo tradiciul preparatebtan ertad sakmaod efeqturi gamodga [1,2]. literaturasi arwerilia omeprazolisa da leqsotanis kombinirebuli mirebisas am preparatebis koncentraciis monitoringi pacientta sisxlis plazmasi. igi xorcieldeba maralefeqturi sitxuri qromatografiuli metodit, ulraiisferi deteqtirebit 302 da 230 nm talris sigrzeze; preparatebis identifikacias axdenen Sekavebis droebis mixedvit. bromazepamis Sekavebis dro - 8wT; omeprazolis wt; Sida standartad iyeneben oqsazepams [3-5]. leqsotanis farmakokinetikuri kvlevebis Sedegad dadgenil iqna, rom igi kargad gadis hematoencefalur bariers, radgan xasiatdeba benzodiazepinis struqturistvis damaxasiatebeli marali lipotropulobit, misi biologiuri SeRwevadoba aris 80-90%. preparatis peroraluri mirebisas maqsimalur koncentracias arwevs mirebidan 2 st-is Semdeeg. sisxlis plazmis cilebs ukavsirdeba 70 %-it. ganawilebis moculoba Seadgens vd=50l/kg; RviZlSi warmoiqmneba ori metaboliti; Tvlian rom klinikuri mnisvneloba gaacnia 3-hidroqsimetabolits [6,7]. naxevargamoyofis periodi t 1/2 =20 st; klirensi Cl= 40ml/wT; preparatis eqskrecia 2%. xandazmul pacientebsi preparatis t 1/2 SedarebiT ufro xangrzlivia st, amitom am kategoriis pacientebistvis leqsotani warmoadgens riskis jgufs. bromazepamis metabolizmsi monawileobs citoqrom-p-450, romelsac axasiatebs polimorfizmi. aseve arsanisnavia is faqtic, rom preparatis t 1/2 damokidebulia pacientis individualur fenotipze, ris gamoc aucilebelia individualuri pacientistvis farmakokinetikuri monitoringis Catareba usafrtxo da efeqturi farmakoterapiis miznit. leqsotanis metabolizmi da farmakokinetika qartul populaciasi dremde ar aris Seswavlili. aqedan gamomdinare, miznad davisaxet piloturi kvlevis Catareba bromazepamisa da misi dominanti metabolitebis gansazrvrisatvis adamianis nerwyvsi maralefeqturi sitxuri qromatografiuli metodit. arnisnuli metodi sasualebas mogvcems farmakokinetikuri monitoringis Catarebis aucileblobis SemTxvevaSi movaxdinot sisxlis plazmis nerwyvit Canacvleba. kvlevis obieqti: intaqturi adamianis nerwyvi; mdedrobiti sqesis 2 moxalisis nerwyvi, Segrovebuli garkveuli drois intervalsi, romeltac ertjeradad mirebuli hqondat leqsotanis peroraruli tableti dozit 3,0 mg; leqsotanis standartuli nimusi eqsperimentis pirvel etapze davamusavet intaqturi adamianis nerwyvze bromazepamis izolirebis metodikis modeli. kvlevis metodi: maralefeqturi sitxuri qromatografi WATERS ulrtaiisferi da dioduri deteqtorit (DAD) speqtris diapazonit nm; mass-speqtrometri sitxuri qromatografia tandemuri MS/MS silikagelis sveti C1 8 ; mobiluri faza: 242

243 acetonitrili: acetaturi buferi 20:80; gamxsnelis dinebis sicqare 0,3 ml/wt; rejimi izokratuli. nerwyvidan leqsotanis izolirebistvis gamoviyenet cilebis daleqvis klasikuri metodi. damleq reagentad viyenebdit samqlorzmarmjavasa da acetonitrils. eqsperimentis Sedegad, davadginet, rom acetonitrilis gamoyenebit nerwyvis cilebidan bromazepamis gamontavisufleba ufro maqsimalurad xdeboda, vidre samqlorzmarmjavas SemTxvevaSi. aseve mnisvnelovania is faqti, rom samqlorzmarmjavas aqvs mzafri suni da marali agresiuloba, amitom damleq reaqtivad SemdgomSi viyenebdit acetonitrils. intaqtiuri adamianis nerwyvidan bromazepamis izolirebis metodikis modelis damusavebisas intaqtiuri adamianis nerwyvs virebdit piris Rrus satanado higienuri procedurebis Catarebis Semdeg, vagrovebdit sterilur WurWelSi 2 ml raodenobit. sul 5 obieqti. Tu sawiro iyo, nerwyvs vacentrifugebdit 10 wt-is ganmavlobasi 5000 br/wt-ze. gamwvirvale zeda fena gadagvqonda 5 ml-is moculobis mqone konteinersi: xutive konteinersi vatavsebdit TiTo ml nerwyvs da Segvqonda preparatis mzardi koncentraciis xsnarebi: 20 ng/ml; 30 ng/ml; 40 ng/ml; 60 ng/ml; 80 ng/ml-si Sesabamisad. konteinerebs vatavsebdit macivarsi C-ze 30 wt-is ganmavlobasi. Semdeg otaxis temperaturaze vumatebdit TiTo ml acetonitrils, vanjrrevdit 5 wt-is ganmavlobasi meqanikur sanjrrevelaze da vacentrifugebdit 1500 br/wt wt-is ganmavlobasi. avtomaturi pipetis daxmarebit virebdit supernantis zeda gamwvirvale fenas da vaortqlebdit rotaciul amaortqlebelze. nasts vxsnidit 50 mkl etanolsi da Segvqonda qromatografsi. deteqtirebas vaxdendit 254 nm-ze. bromazepamis qromatografirebis pirobebi arwerilia zemot. bromazepamis pikebis identifikacia xdeboda Sekavebis drois mixedvit wutebsi. vagebdit sakalibro grafikebs, xuti paraleluri cdis monacemebis safuzvelze. Cvens SemTxvevaSi korelaciis koeficienti K kor = ; rac miutitebs metodis sizustes da saimedoobas (K kor warmoadgens preparatis pikebis simarlesa da koncentraciebs Soris fardobas 5 paraleluri cdis dros). sakalibro grafiki gamodis koordinatta sistemis nulovani wertilidan, rac uzrunvelyofs metodis sworxazovnebas da sizustes. Cvens mier mirebuli eqsperimentuli monacemebis metrologiuri damusavebis Sedegebi warmodgenilia cxrilis saxit (cxrili 1). cxrili 1. intaqturi adamianis nerwyvsi bromazepamis raodenobrivi analizis Sedegebis metrologiuri damusaveba Setanili bromazepamis standartuli substancia ng. - Si bromazepamis armocenili raodenoba %-Si n 243 bromizopamis Semcveloba % S metodis cdomileba %-Si

244 n-eqsperimentebis raodenoba; -,+%- bromazepamis sasualo raodenoba xuti cdis Sedegad; S-TiTo cdaze mirebuli sasualo standartuli gadaxra rogorc cxrilidan Cans, acetonitrilit SesaZlebelia nerwyvidan izolirebuli iqnas preparatis sasualod 83.6%, rac sruliad sakmarisia bromazepamis koncentraciis monitoringis Casatareblad. mowodebuli metodi aprobirebuli iqna klinikur masalaze. moxalise pacientebs ezleodat leqsotanis tableti dozit 3,0 mg dilit, msubuqi sauzmis Semdeg; nerwyvis Segroveba xdeboda preparatis mirebidan drostan dinamikasi: 0.5, 1.5, 4 da 8 st-is ganmavlobasi. nerwyvis damusaveba warmoebda zemot mowodebuli metodikis mixedvit. bromazepamisa da misi metabolitis qromatogramebi warmodgenilia suratebze 1 da 2. sur. 1. bromazepamisa da 3-hidroqsibromazepamis qromatograma (piki #1 bromazepamis Sekavebis dro 0.88wT; piki #2 metaboliti 3-hidroqsibromazepamis Sekavebis dro 1.55wT; piki # 3 ucnobi piki Sekavebis dro wT) qromatogramaze mirebuli bromazepamis pikebis fartobebis mixedvit vsazrvravdit mat koncentraciebs da vagebdit farmakokinetikur mruds (sur. 2). sur. 2. adamianis nerwyvsi bromazepamis koncentraciis dinamika rogorc farmakokinetikuri mrudidan Cans, bromazepamis koncentracia maqsimums arwevs 2 st-si; 2-4 st-mde SenarCunebulia SedarebiT stabiluri koncentracia, xolo 4 st-is Semdeg iwyeba koncentraciis swrafi vardna. 6 st-si preparatis koncentracia nerwyvsi Seadgens 5ng/ml-s. 8sT-is Semdeg ukve verar ganvsazrvret preparatis raodenoba. radgan metodis mgrznobeloba preparatis koncentraciaze dabalia. 244

245 literaturuli monacemebit dadgenilia adamianis sisxlis plazmasi bromazepamis armosaceni minimaluri da maqsimaluri koncentraciis zrvrebi, romelic meryeobs ng/ml-si. swored es gvazlevs sasualebas plazmis nacvlad gamoviyenot nerwyvi. bromazepamis koncentraciis monitoringis Casatareblad. aseve SesaZlebelia bromazepamis identifikaciisa da raodenobrivi gansazrvrisatvis sasamartloeqspertizis miznit biologiur masalad nerwyvis gamoyeneba. daskvna: 1. dadgenil iqna intaqturi adamianis nerwyvidan bromazepamis izolirebis optimaluri pirobebi. acetonitrilit SesaZlebelia nerwyvidan preparatis izolireba 82,5 %-it. 2. damusavebul iqna bromazepamis da misi aqtiuri metabolitis 3-(OH)- hidroqsibromazepamis igiveobisa da raodenobrivi gansazrvris maralefeqturi sitxuri qromatografiuli metodi ui deteqtirebit 254 nm-ze. Catarebul iqna metodis validacia metodi xasiatdeba a) specifikurobit, radgan metodit SesaZlebelia qromatografiulad daiyos bromazepami da misi aqtiuri metaboliti 3- hidroqsibromazepami Sekavebis droebit: 0.88 wt da 1.55 wt Sesabamisad; b) sworxazovnebit, radgan sakalibro grafiki gamodis koordinatta sistemis nulovani wertilidan. g) sarwmunoebit, radgan korelaciis koeficienti is farglebsi, pikis fartobebisa da koncentraciebis Tanafardoba 1.0-Tan miaxloebulia. d) maralmgrznobiarobit SesaZlebelia preparatis koncentraciis gansazrvra 5ng/ml-Si, rac sruliad sakmarisia preparatis analizis Casatareblad racionaluri farmakoterapiis miznit. 3. Seswavlil iqna adamianis nerwyvsi bromazepamis koncentraciis dinamika 3 mg leqsotanis ertjeradi peroraluri tabletis mirebis Semdeg. 4. Catarebuli piloturi kvlevis Sedegebis safuzvelze SegviZlia vivaraudot, rom bromazepamis farmakokinetikuri monitoringis Casatareblad SesaZlebelia adamianis sisxlis plazmis nerwvit Canacvleba pacientta efeqturi da usafrtxo farmakoterapiis miznit. literatura 1. Johnston, M. Anxiety in surgical patients. Psychol. Med. 1980; 10(1): Gomes L.C., Fraga M.N. Illness, hospitalization and anxiety: an approach to mental health. Rev. Bras. Enferm. 1997; 50(3): Le Solleu H., Demotes-Mainard F., Vincon G., Bannwarth B. The determination of bromazepam in plasma by reversed-phase high-performance liquid chromatography. J. Pharm. Biomed. Anal. 1993; 11(8): Andraus MH, Wong A, Silva OA, Wada CY, Toffleto O, Azevedo CP, Salvadori MC. Determination of bromazepam in human plasma by high-performance liquid chromatography with electrospray ionization tandem mass spectrometric detection: application to a bioequivalence study. J Mass Spectrom. 2004; 39(11): Cristina Iuga, Mirela Moldovan, Adina Popa, S.E. Leucuţa. Validation Of Hplc- Uv Method For Analysis Of Omeprazole In Presence Of Its Metabolites In Human Plasma. J. Farmacia 2008; LVI (3): Rieck W., Platt D. High-performance liquid chromatographic method for the determination of alprazolam in plasma using the column-switching technique. J. Chromatogr. 1992; 578 (2): Cook J.M. Marshall R., Masci C., Coyne J.C. Physicians perspectives on prescribing Benzodiazepines for older adults: a qualitative study. J Gen Intern Med 2007; 22(3): Jones W., Holmger A. Concentrations of scheduled prescription drugs in blood of impaired drivers: considerations for interpreting the results. Theirdrug Moint 2007; 29(2): Rezk N.L., Brown K.C., Kashuba A.D. A simple and sensitive bioanalytical assay for simultaneous determination of omeprazole and its three major metabolites in human blood plasma using RP-HPLC after a simple liquid-liquid extraction procedure. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2006; 844 (2): reziume leqsotanis (bromazepamis) gansazrvra adamianis nerwyvsi maralefeqturi sitxovani qromatografiuli metodit 245

246 kunwulia l., surgulaze T., maxaraze r., bojaze a., ioramasvili h. Tbilisis saxelmwifo samedicino universiteti, farmacevtuli da toqsikologiuri qimiis departamenti, saqartvelo leqsotanis arapatenturi saxelwodebaa bromazepami. damusavebul iqna pacientis nerwyvsi bromazepamisa da misi aqtiuri metabolitis 3-(OH)-hidroqsibromazepamis igiveobisa da raodenobrivi gansazrvra maralefeqturi sitxuri qromatografiuli metodi ui deteqtirebit 254 nm-ze. Catarebul iqna metodis validacia. metodi xasiatdeba: specifikurobit, sworxazovnebit, marali mgrznobelobit, kvlavwarmoebulobit, saimedoobit. piloturi kvlevis Sedegebis safuzvelze SesaZlebelia vivaraudot, rom bromazepamis farmakokinetikuri monitoringistvis SesaZlebelia adamianis sisxlis plazmis nerwvit Canacvleba pacientta racionaluri farmakoterapiis miznit. SUMMARY DETERMINATION OF LEXOTAN (BROMAZEPAM) IN SALIVA BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY METHOD Kunchulia L., Surguladze T., Makharadze R., Bozhadze A., Ioramashvili H. Tbilisi State Medical University, Department of Pharmaceutical and Toxicological Chemistry, Georgia Bromazepam is generic name of Lexotan. It belongs to anxiolytic drug. By the authors of presented article was determined bromazepam and its dominant metabolite 3-(OH)- hydroxybromazepame in saliva of patient by high performance liquid chromatography method (DAD, 254 nm). Method was validated according linearity, specificity, sensitivity, repeatability, accuracy. Based on the results of pilot research it is possible to assume that during pharmacokinetic analysis human blood plasma might be replaces by saliva with purpose of rational pharmacotherapy. qsanaqsisa (alprazolamis) da misi dominanti metabolitis gansazrvra adamianis SardSi maralefeqturi sitxuri qromatografiuli metodit lejava l., kunwulia l., bojaze a., joxaze m., lekisvili n. Tbilisis saxelmwifo samedicino universiteti, farmacevtuli da toqsikologiuri qimiis departamenti, saqartvelo qsanaqsi _ axali Taobis trankvilizuri sasualeba sintezirebul iqna 1960 wels. misi arapatenturi saertasoriso saxelwodebaa alprazolami. qsanaqsi saqartvelos farmacevtul bazarze 1990-iani wlebidan gamocnda da maleve miiqcia samedicino sazogadoebis yuradreba, rogorc efeqturma tranqvilizurma preparatma [1-3]. ass Catarebuli premarketinguli fartomasstabiani kvlevebis Sedegad, romelsic 531 pacienti monawileobda dadgenil iqna qsanaqsis farmakokinetikuri parametrebi. ganawilebis moculoba ml/70kg-ze; cilebtan SekavSireba 99%; klirensi 5.4 ml/wt; naxevargamoyofis periodi T 1/2 15.8sT; efeqturi koncentracia 300 ng/ml; toqsikur koncentraciaze ar aris sarwmuno monacemebi [4,5]. Seswavlilia qsanaqsis 246

247 farmakokinetikaze sxvadasxva egzogenuri da endogenuri faqtorebis gavlena. magalitad, preparatis naxevargamoyofis periodis sidide icvleba asakobriv aspeqtsi _ axalgazrdebsi t 1/2 Seadgens 11 st, xolo xandazmulebsi st; msuqan pacientebsi st; alkoholikebsi st [6,7]. alprazolami gadis transplacentur bariers, aseve misi eqstraqcia xdeba rzit. dedis rzestan ertad Cvil bavsvebsi gadadis preparati da iwvevs toqsikur movlenebs, letargiul Zils da suntqvis datrgunvas [8,9]. alprazolamis farmakokinetikaze gavlenas ar axdens sqesi. mwevelebsi alprazolamis koncentracia sisxlsi Semcirebulia 50 %-it, vidre aramwevelebsi. gansakutrebit mnisvnelovania farmakokinetikuri interferenciis gavlena qsanaqsisa da sxva preparatebis ertdrouli danisvnisas. radgan xsir SemTxvevaSi adgili aqvs arasasurveli efeqtebis ganvitarebas. magalitad, dadgenil iqna benzodiazepinebisa da cefalosporinebis ertdrouli mirebisas toqsikuri efeqtebis gazliereba da arwerilia letalobis SemTxvevebi. SvedeTSi Karolinska-s institutsi Seswavlil iqna qsanaqsis metabolizmze sxvadasxva farmakologiuri jgufis preparatebis gavlena. radgan qsanaqsis metabolizmi citoqrom p-450 monawileobit mimdinareobs, aucilebelia im preparatebis codna, romlebic warmoadgenen citoqrom p-450 is induqtorebsa da inhibitorebs [7]. qsanaqsit efeqturi da usafrtxo farmakoterapiis miznit Catarebul iqna sakmaod seriozuli kvlevebi. qsanaqsisa da aminoglikozidebis jgufis preparatebis kombinirebuli mirebis dros. gansakutrebit sasisia eritromicinis, klaritromicinis, oleandromicinisa da qsanaqsis ertdrouli danisvna, radgan am preparatebis metabolizmsi monawileobs ertidaigive fermenti citoqrom p-450 aminoglikozidebi warmoadgenen citoqrom p-450-is inhibitorebs, ris gamoc mcirdeba qsanaqsis metabolizmis sicqare, an saertod arar xdeba misi metabolizmi. mcirdeba eliminacia, izrdeba preparatis koncentracia plazmasi, mrudqvesa farti AUC, ganawilebis moculoba VD, da t 1/2. dadgenil iqna, rom citoqrom p-450 gaacnia izofermentebi. saintereso kvlevebi iqna Catarebuli sxvadasxva erebsi qsanaqsis metabolizmis Seswavlis mxriv. eqsperimentsi monawileobda 144 tanzanieli da 26 Svedi. dadgenil iqna, rom citoqrom p-450-is ori izofermenti monawileobs preparatis metabolizmsi. CYP3A4 SvedebSi ufro aqtiuria da miireba metaboliti alfa-hidroqsialprazolami, xolo tanzanielebsi alprazolamis metabolizmsi monawileobs izofermenti CYP3A5 da miireba 4-hidroqsialprazolami [4]. saqartvelosi alprazolamis farmakokinetika da metabolizmi ar aris Seswavlili. am mimartulebit kvlevebis Catareba upriania, rata dadgenil iqnas qartul populaciasi alprazolamis metabolizmis xasiati, kerzod, citoqrom p-450-is romeli izofermenti irebs monawileobas da dadgenil iqnas dominanti metabolitis struqtura. am kvlevebis Sedegad perspeqtivasi SesaZlebeli iqneba pacientta biologiur masalasi: SardSi, sisxlis plazmasi, nerwyvsi alprazolamisa da misi aqtiuri metabolitebis koncentraciis gansazrvra და farmakokinetikuri monitoringis Catareba pacientis usafrtxo da efeqturi mkurnalobis miznit. kvlevis mizani. alprazolamisa da misi dominantი metabolitis gansazrvra adamianis SardSi maralefeqturi sitxuri qromatografiuli metodit; Sardidan alprazolamis metabolitis izolirebis optimaluri pirobebis dadgena. kvlevis obieqti: qsanaqsis tabletebi dozit 0.25mg. 247

248 alprazolamis laboratoriuli standarti, romelic Cvenს mier iqna gamoyofili tabletebidan. pacientis Sardi, preparatis mirebamde da mirebis Semdeg. kvlevis metodebi: maralefeqturi sitxuri qromatografiა. ქრომატოგრაფი Waters, dioduri deteqtori (DAD). es ukanaskneli xasiatdeba speqtris farto diapazonit nm; sitxuri qromatografia _ tandemuri mass-speqtrometriit MS/MS. Txelfenovani qromatografia silikagelis sorbentit minis firfitaze. eqsperimentsi monawileobda 2 moxalise. erti 60 wlis qalbatoni, meore moxalise 24 wlis qalisvili. orive moxalise dilit msubuqi sauzmis Semdeg Rebulobda 0.5 mg qsanaqsis tablets. Sardis Segroveba xdeboda sterilur WurWelSi 48 st-is ganmavlobasi. Sardi inaxeboda gril adgilas, sibnelesi. Sardis damusaveba: Segrovebuli Sardidan virebdit 200 ml. s, vumatebdit 0.1 mol natriumis hidroqsids ph = მლ; eqstraqcias vaxdendit 100 ml etilis eterit 15 wt is ganmavlobasi. eqstraqts vacentrifugirebdit 1500br/wT 10wT-iT. eterian fazas vamatebdit 10 ml gamoxdil wyals Sardis endogenuri hidrofiluri naertebis mosacileblad, vanjrrevdit 3-5 wt-is ganmavlobasi, Semdeg isev vacentrifugirebdit 1500 br/wt 5-10 wt-it. eterian fenas vacilebdit wylians da vaxdendit reeqstraqcias. eterian fenas vumatebdit 5 ml 0.1 mol gogirdmjavas da vaxdendit eqstragirebas 5 wtit. alprazolami da misi metabolitebi gadadis mjava fazasi. vaxdendit fazebis dayofas mikro gamyofi ZabriT. sabolood qveda mjava fazas ganmeorebit vamatebdit 0.1 mol natriumis hidroqsidit ph= მდე Semdeg vaxdendit eqstraqcias ertxel 10 ml eterit da nasts vxsnidit 5 ml etanolsi. obieqti Segvqonda silikagelis minis firfitaze zomit 15X15 sm. mowmed laboratoriuli alprazolamis standartuli nimusis etanoliani xsnaris 10 mkg. firfitas vatavsebdit gamxsnelta sistemasi: qloroformi - acetoni - amiaki 25% - (50:50:1). firfitas vamjravnebdit ui Suqze 254 nmze. alprazolami izleva cisfer laqas Rf ±0.05; xolo metaboliti fluoresencirebs lurji feris laqad Rf ±0.05. samedicino lancetit vaxdendit alprazolamisa da metabolitis amofxekas sorbentidan cal-calke. TiToeuli nimusis eqstraqcias vaxorcielebdit gamxsnelta narevit: etilis eteri - metanoli (7:3) da vinaxavdit Sesaferis konteinerebsi macivarsi mati Semdgomi kvlevebis miznit. Sardidan mirebuli eqstraqtebis analizs, mati damusavebis Semdeg vatarebdit maralefeqtur sitxur qromatografze. marka - HPLC (Waters). dioduri ultraiisferi deteqtori, talris sigrze 254nm; sveti-silikageli C 18, mobiluri faza : acetonitrili : acetaturi buferi (20:80), gamxsnelis dinebis sicqare 0.3 ml/wt; rejimi izokratuli. alprazolamisa da misi metabolitis identifikacia movaxdinet Sekavebis drois mixedvit (sur 1). 248

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