Citrustem. Orange stem cells. Organizes the inner structure of the skin for a younger appearance ANTI-AGING

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1 December 14

2 Orange stem cells. Organizes the inner structure of the skin for a younger appearance ANTI-AGING

3 » The architect of the skin Stem cells from orange for a sustainable beauty Organizes and redensifies the dermis structure Repairs extracellular matrix Improves cellular adhesion The skin recovers the elasticity it had 12 years ago. Softer and more velvety complexion Global younger appearance

4 » Aging and order When we age, many biological processes in our skin slow down: 1. Fibroblasts lose their proliferative capacity and functionality. 2. They synthesize less structural elements. 3. Collagen and elastin fibers become scarce and disordered. 4. Disorganized and unstable extracellular matrix.

5 » Aging and order As a result, dermis loses density and the skin shows signs of aging: Elasticity decreases and wrinkles appear. The microrelief structure becomes anisotropic skin loses softness and velvety touch. Keeping the skin inner structure organized is essential for a younger looking skin

6 » The architecture of the skin The dermis is the foundation of the skin structure Various components are involved in its assembly and distribution, such as: 1. Collagen VI network. 2. Elastin. 3. ADAMTS2. In the epidermis, essential elements for an ordered structure can also be found, such as: 4. Keratinocyte transglutaminase (TGK).

7 » The architecture of the skin Stratum corneum Epidermis Papillary dermis Reticular dermis Collagen VI network, the organizer It is mainly found in the papillary dermis. Functions: 1. Cell adhesion. 2. Mediator of cell-matrix interactions. Hypodermis With age, the synthesis of collagen VI decreases The skin extracellular matrix becomes disorganized and unstructured

8 » The architecture of the skin Elastin, the protein of youth: Together with fibrillin, it is the structural component of elastic fibers Gives elasticity and resistance to the skin. ADAMTS2, the facilitator: ADAMTS2 is the responsible of cleaving the N-propeptides of procollagen to form collagen. The fibers that give tensile strength will be developed; they are responsible for the dermis structure. Levels of elastin and ADAMTS2 decrease with age Skin loses elasticity and resistance, and wrinkles appear

9 » The architecture of the skin Keratinocyte transglutaminase, epidermal stabilization: TGK is an essential enzyme for the assembly and organization of the epidermal barrier structures. It is expressed in the spinous and granular layers. TGK levels are reduced as years pass by Skin loses density, soft and velvety touch, and the desquamation is altered

10 » What are stem cells? Undifferentiated cells found in all multicellular organisms. In plants, they are totipotent stem cells able of regenerating the entire plant Its maintenance depends on: Signs coming from the microenvironment. Epigenetic control: keeps stem cells undifferentiated.

11 » Provital stem cells collection Provital is developing a new line of active ingredients based on plant stem cells., obtained from orange stem cells (Citrus sinensis) with anti-aging effect, is the first launching of Provital Stem Cells Collection.

12 », sustainable beauty Orange stem cells are obtained from a renewable source of plant material: No dependence on orange natural availability. Origin and traceability known in depth. Sustainable and ecological cultivation. To obtain 1 kg of orange extract = 45 litres of water; 1 kg of = 0.95 litres of water. Obtention of stem cells without genetic modifications. From a cell lysate without solvents. is a natural, sustainable and environmentally responsible active

13 » In vitro efficacy: effect on fibroblasts Modulation of gene expression A study, in which 64 genes were included, was conducted to evaluate the effect of 0.1%. GeneID Gene % Control COL6A1 Collagen, type VI, alpha ELN Elastin 251 ADAMTS2 ADAM metallopeptidase with thrombospondin type 1 motif, increases the expression levels of these genes, which are able to improve the extracellular matrix structure

14 » In vitro efficacy: effect on fibroblasts Stimulation of proliferation Evaluation of the effect on the proliferation capacity of aged human dermal fibroblasts (P17-NHDF). Cell Treatment % Control (0.03%) 108 P17-NHDF (0.1%) 111 (0.3%) 123 stimulates the proliferation of fibroblasts increases the synthesis of collagen and other extracellular matrix key elements

15 » In vitro efficacy: effect on keratinocytes Stimulation of keratinocyte transglutaminase (TGK) production Evaluation of the effect of on the TGK production capacity of keratinocytes. 700% 600% 500% 400% 300% 200% 100% 0% 697% 199% 161% 100% Control (0.03%) (0.1%) CITRUSTEM (0.3%) increases the production of TGK better organization and assembly of epidermal structures more structured skin

16 » In vivo efficacy: protocol The efficacy of has been evaluated in vivo: A panel of 20 women, aged between 41 and 55 years (average=49.4). Application of a 3% formulation and also a placebo. Applied twice a day during 56 days.

17 » In vivo efficacy: effect on skin Sharpness of the microrelief It was evaluated by a trained expert by clinical score on a 13 point scale (0 = no microrelief lines 12 = regular lines with well defined polygons). Sharpness Product T0 T56 % increase Placebo (3%) Placebo 10.4 Active, T0 Active, T56 Microrelief improvement is the visible result of a well organized and structured dermis

18 » In vivo efficacy: effect on skin Stratum corneum quality It was evaluated by clinical score on a 13 point scale (0 = uncohesive stratum corneum with numerous squames; 12 = smooth surface without squames). Skin appearance Product T0 T56 % Increase Placebo (3%) Placebo 11.6 The stratum corneum is more cohesive, with fewer scales, and skin shows a silky aspect and is smooth to the touch

19 » In vivo efficacy: effect on skin Biomechanical properties The ratio Ur/Uf (R7) represents the biological elasticity (retraction to the total deformation). Ur/Ue (R7) Product T0 T56 % Increase Placebo (3%) Placebo With, your skin will recover the elasticity that had 12 years ago

20 » In vivo efficacy: effect on skin Biomechanical properties The ratio of Ur/Ue (R5) represents elastic recovery (the ability of the skin to recover after deformation). Ur/Ue (R5) Product T0 T56 % Increase Placebo (3%) Placebo improves the elastic recovery of the skin

21 » In vivo efficacy: clinical evaluation Skin radiance Skin appearance was evaluated by a trained assessor by visual scoring from 1 to 9 (higher values indicate a better complexion). Radiance Product T0 T56 % Increase Placebo (3%) Placebo 8.5 renews skin overall appearance

22 » In vivo efficacy: clinical evaluation Skin firmness Skin appearance was evaluated by a trained assessor by visual scoring from 1 to 9 (higher values indicate a better complexion). Firmness Product T0 T56 % Increase Placebo (3%) Placebo 6.52 increases skin firmness

23 » In vivo efficacy: clinical evaluation Skin wrinkles Skin appearance was evaluated by a trained assessor by visual scoring from 0 to 6 (lower values indicate a smoother skin). Wrinkles Product T0 T56 % Decrease Placebo (3%) Placebo 6.72 diminishes wrinkles

24 » Conclusions : Increases the expression of some genes, which are able to improve extracellular matrix structure. Organizes and redensifies the dermis structure. Regular and well defined microrelief. The skin recovers the elastic properties it had 12 years ago. Renewed skin appearance, fewer wrinkles and improved overall appearance.

25 » Cosmetic applications Global anti-aging lines Cosmetic products for skin rejuvenation Anti-aging preventive cosmetics Cellular regenerator Intensive facial treatments Treatment make-up

26 » Technical information Viscous liquid. White pale yellow color. Soluble in aqueous solutions. Dose: 2 4 %. China approved

27 PROVITAL. S.A. Pol. Ind. Can Salvatella Gorgs Lladó, Barberà del Vallès Barcelona (España) Tel. (+34)

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