SPE ANTEC Anaheim 2017 / Lubrizol LifeSciences, Brecksville, OH

Transcription

1 Tecobax A New Class of Non-softening Thermoplastic Polyurethanes for Medical Applications Anthony Walder 1, David Cozzens 1, Walid Qaqish 2, Michael J. Wiggins 2, Murty Vyakarnam 2 1 Lubrizol LifeSciences, Wilmington, MA 2 Lubrizol LifeSciences, Brecksville, OH Abstract Thermoplastic polyurethanes (TPUs) are a class of thermoplastic elastomers (TPEs) that are used in a variety of medical applications (1). Their characteristics including low temperature flexibility, excellent abrasion resistance, high tensile strength, good processing characteristics, and biocompatibility make them particularly attractive for medical applications by the device design engineers. In general current medical grade TPUs have the unique property of undergoing a reduction in flex modulus when placed in the body (2). This characteristic is referred to as softening. A new class of TPUs has been developed that retains many of the characteristics found attractive by designers but now offers the non-softening characteristic, broadening the design space for TPUs in medical devices. A non-softening TPU may be an attractive material for use in percutaneous interventional catheters where retention of stiffness is desired to enhance trackability and torqueability. Three grades of non-softening TPUs, covering low to mid durometers have been introduced into the market: Tecobax 25D, 40D, and 45D. The performance characteristics of these TPUs were measured and compared to other softening TPUs as well as non-softening TPEs. These materials maintain many of the typical TPU characteristics which make them widely used. For example, the 25D, 40D and 45D durometers have excellent tensile strengths and abrasion resistance. Softening characteristics were tested by comparing flexural modulus values at ambient conditions (22 C, 50% RH) to body conditions (100% RH, 37 C). The degree to which these new materials soften, especially in the harder grades, is significantly less than other TPUs but is comparable to non-softening TPEs. Torqueability at body conditions is also comparable to common non-softening TPEs. These materials also offer other unique characteristics which are of particular interest to the medical device community. For example, these materials have a high Vicat softening temperature; the 40D and 45D are above 100 C, resulting in compatibility with steam sterilization. In addition, these materials produce excellent quality extrusion components using standard extrusion equipment. Other unique characteristics and potential medical applications will be discussed. Introduction Thermoplastic polyurethanes (TPUs) are a class of thermoplastic elastomers (TPEs) (3). TPUs are generally made from diisocyanates and diols. The diols can either be of high molecular weight, known as a polyol, or low molecular weight, known as a chain extender. These materials are segmented copolymers with alternating hard and soft blocks. The hard segment is comprised of diisocyanate and chain extenders. The soft segment is predominantly comprised of polyol. The hard segment which typically has the high glass transition (Tg) temperature imparts strength while the soft segment which typically has the low glass transition temperature imparts flexibility. Because they are thermoplastic, they can be easily processed by common melt processing techniques such as extrusion to produce film, sheet, or tubing, and injection molding to produce parts with complex three dimensional geometries. Thermoplastic polyurethanes can be classified in many different categories. The major categories include those defined by physical aspects, e.g. hardness, and the chemistry of the diisocyanate SPE ANTEC Anaheim 2017 / 1885

2 and polyol monomers used to synthesize the polymers. The typical hardness range for TPUs is from 70A (elastomeric polymers) to 85D (engineered polymers). Softer TPUs (50A-70A) are also commercially available. TPU hardness is generally controlled by adjusting the hard and soft segments ratio. Plasticizers can also be used to create softer durometer TPUs (4). TPUs can also be categorized by the soft segment or the polyol they are based on, e.g. ether, ester or carbonate. Esters are known for their strength and oxidative stability, while ethers are known for their low temperature performance and hydrolytic stability. Polycarbonates combine the oxidative stability and strength of the esters and the hydrolytic stability of the ethers. The polycarbonate based TPU are generally accepted to be more biostable than esters and ethers when implanted in the body (5). This paper introduces a new class of TPUs that relies on classic polyurethane synthesis routes, but produces a highly resilient polymer with unique non-softening characteristics. These TPUs have been synthesized using both batch and continuous processing and in the range of 25D to 75D. A variety of soft segment chemistries are possible, e.g. polyether, polyester, and polycarbonate. This paper will focus on TPUs based on aliphatic isocyanate and polyether polyol with hardnesses in the range of 25D to 45D. Experimental The polymers studied in this paper were synthesized by Lubrizol using the batch process with commercially available aliphatic isocyanates and polyether polyols. Three grades were studied: Tecobax 25D, 40D, and 45D. For all thermal processing, resins were dried to 0.05% moisture or less using a forced air desiccant drying system prior to processing. Film extrusion was performed on a 25mm diameter single screw extruder with a 24/1 length to diameter ration. A 3 to 1 compression ratio barrier screw (20/40/40 feed/transition/metering) was used. The breaker plate filter used a 250 mesh filter (screen). During extrusion, a standard ramping temperature profile was adjusted to obtain 3 to 15 MPa extruder pressure. To evaluate extrusion quality, a slit die and a 4:1 draw down ratio was used to produce 0.25mm thick films. Extrusion quality was judged by an internal quality system based on the TAPPI Dirt Estimation Chart T564. Imperfections of the films were evaluated based on size and number. Film quality was also evaluated qualitatively by comparing to other commercial polyurethanes. To evaluate tensile strength, the same slit die was used and a 2:1 draw down ratio to produce a 0.5mm thick film. The tensile strength of the film samples were obtained by ASTM D412, Die C. Thickness was measured using a drop gauge. Die-cut dog bones specimens were conditioned at 50% relative humidity and 22 C prior to testing. The strain rate was 50 cm/minute (20 inches/minute). Injection molded samples were prepared using dried resin (0.05% or less moisture content) for Bay Shore rebound and flexural modulus testing. For rebound testing, a 90 ton injection molding unit was used to produce samples; testing was done according to ASTM D2632. For flexural modulus, a 60 ton injection molding unit was used with a cavity that was 1 (25 mm) by ¼ (8 mm) by 6 (150 mm). Injection molded bars were preconditioned at ambient conditions for 5 days minimum prior to testing. To determine the softening characteristics at body conditions, the molded bars were placed in 40 C water bath for a minimum of 3 days. The flexural modulus was then tested using a three point test per ASTM D790 and compared to results from dry samples. A 50 ton hydraulic press was used to make compression molded plaques (7.0 x x 7.0 ) for static coefficient of friction (COF). COF was measured for polymer-on-polymer in both dry and wet (dh2o at 20 C) conditions per ASTM D1894. SPE ANTEC Anaheim 2017 / 1886

3 For torqueability testing, tubing was extruded on a 25mm, 24/1 extruder using a general purpose screw. Final dimensions were outer diameter by inner diameter. In general, a ramping profile was used with the metering section set at 180 C. Torqueability testing was performed at Machine Solutions Inc. (Flagstaff, AZ) using the interventional device testing equipment (IDTE-2000) commonly used to evaluated catheters systems. The testing was performed at 37 C and in normal saline per internal procedure. Samples of other TPUs and TPEs were prepared by Lubrizol in similar ways to those described above, i.e. same dimensions, similar processing parameters, for comparative testing. Biocompatibility testing was performed on the extrusion quality films at Toxikon (Bedford, MA). These films are cleaned/sterilized with a 99% isopropyl alcohol (Aldrich, Milwaukee WI) wipe and allowed to dry 16 hours. Specifically, L929 MEM Cytotoxicity testing per ISO was performed on Tecobax 25D, 40D, and 45D in compliance with good laboratory practices (GLP). In addition, Tecobax 25D and 45D were tested in Hemolysis, Systemic Toxicity, Intracutaneous Toxicity, and Intramuscular Implantation testing in accordance with ISO procedures. Tecobax 25D, 40D, and 45D extruded films were exposed to gamma radiation (25KGy and 50KGy), Ethylene Oxide (standard cycle), and steam (autoclaved steam sterilized at one and ten cycles at 121 C for 30 minutes per cycle). The ultimate tensile strength (UTS) was measured using ASTM D412 following sterilization. Vicat Softening (ASTM D1525) was performed on injection molded Tecobax 25D, 40D, and 45D which were compared to the corresponding copolyamide durometers. The flat molded samples are tested with load applied to a needle penetrator to provide specified maximum force. The test samples are then immersed in a heattransfer medium, which is heated at a specified constant rate (120 C/hr, 10N). The temperature of the medium is recorded when total penetration of the needle has reached a depth of 1mm (0.04 ). Results The three Tecobax grades processed easily on both standard lab scale and production scale thermal processing equipment. The extrusion quality films passed the internal quality system based on the TAPPI Dirt Estimation Chart T564. Extruded tubing showed good clarity and was qualitatively similar to other TPEs used for balloon blowing. The tensile strength and ultimate elongation of Tecobax is compared to other medical grade TPUs and copolyamide in Table 1. Tecobax has strength and ultimate elongations to break typical of TPUs (6). Table 1: Tensile Strength and Ultimate Elongation of Tecobax Compared to Other Common TPUs and Copolyamide. Shore Chemistry Tensile Strength/ Elongation (MPa/%) 25D/75A Tecoflex 41/ 720 Tecothane 37/ 580 Aliphatic 50/ 600 Carbothane Aromatic 55/ 400 Carbothane Tecobax 39/ 800 Copolyamide 29/ D/95A Tecoflex 69/ 410 Tecothane 59/ 420 Aliphatic 66/ 400 Carbothane Aromatic 69/ 370 Carbothane Tecobax 56/ 650 Copolyamide 46/ 850 Shore rebound was used to demonstrate the resiliency of the materials. Table 2 shows the rebound characteristics as a function of material and hardness. Soft TPUs generally have good resiliency characteristics but as the material increases in hardness the rebound decreases. SPE ANTEC Anaheim 2017 / 1887

4 Coefficient of Friction However, with the Tecobax materials the resiliency remains high at harder durometers. Table 2. Resiliency of Tecobax Compared to Polyether TPUs and TPEs as Measured by Shore Rebound. Shore Chemistry 25D/75A Tecoflex 51 Tecothane 44 Tecobax 47 Copolyamide 45 45D/95A Tecoflex 31 Tecothane 30 Tecobax 48 Copolyamide 39 Shore Rebound (%) Flexural modulus measured from molded bars was used to compare the softening characteristics of Tecobax to other TPUs as well as the competitive copolyamide. The molded bar had sufficient mass to provide an accurate measure of the bend force of the soft materials; measuring compression kink of a thin walled tube was not sensitive enough to detect differences in softening due to large errors in measurement. Before testing, samples were placed in water at 40 C for a minimum of 3 days to allow samples to reach equilibrium. Table 3 shows the percent softening of the material as calculated by comparing the flexural modulus of the ambient sample to the water/40 C sample. At the softer 25D durometer, TPUs showed a large range of softening, between 10 and 45%. Tecobax and copolyamide were on the low end of softening at 16 and 21%, respectively. At the harder durometer, 45D, the difference in softening characteristics are more dramatic. For both durometers, Tecobax softening was similar to copolyamide. The dry and wet (dh2o at 20 C) polymer-onpolymer static coefficient of friction (COF) of Tecobax 25D, 40D, and 45D was measured and compared to corresponding durometers of the copolyamide. Figure 1 shows the dry polymeron-polymer static COF and Figure 2 shows the wet polymer-on-polymer static COF. In both wet and dry static COF tests, Tecobax 25D, 40D, and 45D exhibited statistically less COF (p < 0.05) when compared to the corresponding copolyamide durometers. Table 3. Softening Characteristics of Tecobax Compared to Competitive TPUs and TPEs. Shore Chemistry 25D/75A Tecoflex 14 Tecothane 33 Aliphatic 45 Carbothane Aromatic 10 Carbothane Tecobax 16 Copolyamide 21 45D/95A Tecoflex 78 Tecothane 36 Aliphatic 72 Carbothane Aromatic 51 Carbothane Tecobax 21 Copolyamide 20 Tecoflex: Aliphatic Ether Tecothane: Aromatic Ether Aliphatic Carbothane: Aliphatic Carbonate Aromatic Carbothane: Aromatic Carbonate Tecobax: Aliphatic Ether Softening (%) 25D 40D 45D Tecobax Copolyamide Figure 1. Dry polymer-on-polymer static COF of Tecobax 25D, 40D, and 45D compared to the corresponding copolyamide durometers. SPE ANTEC Anaheim 2017 / 1888

5 Coefficient of Friction Wet polymer-on-polymer COF Tecobax Copolyamide competitor copolyamide durometers. Although the Tecobax 25D material melted, 40 and 45D maintained their physical strength which is a unique property for aliphatic TPUs D 40D 45D Figure 2. Wet polymer-on-polymer static COF of Tecobax 25D, 40D, and 45D compared to the corresponding copolyamide durometers. The high rebound and non-softening characteristics of Tecobax suggested favorable performance of Tecobax in some catheter applications requiring 1 to 1 torqueability and strong trackability. Therefore tubing of identical dimensions were extruded and torqueability was measured in saline at 37 C. The torqueability characteristics of Tecobax 45D and a 45D copolyamide are shown in Figure 3. The torque transfer response are the two materials are indistinguishable at long ranges. However, when comparing the first two input revolutions (Figure 3, inset), Tecobax 45D shows a more linear response versus the competitive 45D. The similarity in torqueability were also observed with the 25D and 40D durometers, when compared to the corresponding copolyamide durometer. Because these resilient, non-softening TPUs are being developed for the medical markets, standard biocompatibility testing was done. Tecobax 25D, 40D, and 45D passed the L929 MEM cytotoxicity testing with a Grade 0. Tecobax 25D and 45D passed the hemolysis, systemic toxicity, intracutaneous toxicity, and intramuscular implantation, per ISO To assess compatibility of Tecobax with common sterilization methods, i.e. gamma; ethylene oxide; and steam, the ultimate tensile strength (UTS) of dog bone specimens were measured before and after sterilization. Gamma and ethylene oxide sterilization resulted in no loss in UTS. Figure 4 shows the autoclave results compared to Figure 3. Torqueability of Tecobax 45D versus copolyamide 45D. Figure 4. Effect of Steam Sterilization on Ultimate Tensile Strength of Tecobax 40D and 45D compared to the corresponding copolyamide durometers (Unsterilized versus 1 cycle and 10 cycles). Discussion Thermoplastic polyurethane elastomers are commonly based on two types of polyols, polyester and polyether polyols and the less common polycarbonate polyol. Polyester polyols can be made using several different mechanisms such as the reaction of a diacid and a diol or a molecule that contains both the hydroxyl and acid SPE ANTEC Anaheim 2017 / 1889

6 group. The chemistry may be simple but the number of compounds that can be used to form a polyester polyol is almost endless. The type of the diol(s) and diacid(s) used in polyester polyol impacts the performance of the final TPU that is based on that polyol and its molecular weight. There are many additional molecules that can be used to form a polyester polyol to make polyester based polyurethanes. On the other hand, there are significantly less choices in the polyether class of polyols. Polyether polyols have 2, 3, or 4 carbon chains in their repeating units. The average molecular weight of the commercially available polyether polyols is also limited. The most commonly used polyol in the manufacturing of TPU is poly(tetramethylene ether) glycol (PTMEG) or C4. The poly(ethylene glycol) (PEG) or C2 polyol is not commonly used since PEG is water soluble and brings hydrophilic characteristics to the TPU. The polypropylene glycols (PPG), C3 polyols, are mostly employed to make polyurethane foams rather than TPUs. One of the major reasons is because PPG based TPUs generally have poor physical properties compared to common PTMEG based TPU elastomers. The chemical variety for the polycarbonate polyol is even more limited. The polycarbonate polyols used in this study have poly(alkylene carbonate) structure, which are not based on Bisphenol-A (BPA). The polyol selection also plays an important role in the performance of the TPUs (7). The polyester based TPUs generally have high performance versus cost, are stronger in comparison, have excellent abrasion resistance and oxidative stability. The polyether based TPUs are used where hydrolytic stability is needed with minor sacrifices in strength, abrasion resistance and other attributes when compared to the polyester based TPUs. In general, the polycarbonate based TPU elastomers combine the best performance characteristics between the two categories. They retain their physical properties under thermal aging compared to the polyether TPUs. (8). TPUs are also categorized based on the nature of the diisocyanate used in their structure (i.e. aliphatic and aromatic). The most common aromatic diisocyanate used in manufacturing thermoplastic polyurethanes is methylene diphenyl diisocyanate (MDI). Another wellknown aromatic diisocyanate is 2,4-toluene diisocyanate (TDI). However, TDI is generally not used to make TPUs due to poor performance characteristics of the final polymer. 3,3'- Dimethyl-4,4'-biphenylene diisocyanate (TODI), p-phenylene diisocyanate (PPDI), 1,5- Naphthalene diisocyanates (NDI) are among the other aromatic diisocyanates that are used to make polyurethanes with enhanced physical characteristics. There are also several commercially available aliphatic diisocyanates. Dicyclohexyl methane- 4,4 -diisocyanate, (HMDI), the hydrogenated form of MDI, is probably the most employed aliphatic diisocyanate to make aliphatic TPU elastomers. 1,6-hexamethylene diisocyanate (HDI) is another well-known diisocyanate used in thermoplastic polyurethane formulations for several industrial and medical applications. Other aliphatic diisocyanates such as isophorone diisocyanate (IPDI), have not been used significantly in TPUs and are mostly used in polyurethane dispersions. Similar to TDI in aromatic TPU formulations TPUs based on IPDI exhibit poor physical characteristics. There are also other specialty aliphatic diisocyanates available, however, they are mostly used in niche applications. The way the raw materials are combined determines the final TPU properties. The diisocyanate selection gives the polymer certain physical and chemical attributes. Aromatic diisocyanates based TPUs generally are stronger, have better abrasion resistance, better chemical resistance, and thermal resistance than a similar TPUs produced with an aliphatic diisocyanate. On the other hand, the aliphatic diisocyanates SPE ANTEC Anaheim 2017 / 1890

7 provide better color stability, UV resistance, and flexural characteristics to the final TPU network. In general, the selection of aromatic versus aliphatic TPU is based on performance versus cost. Aliphatic based TPU are more expensive per unit so they are selected for the applications where the performance characteristics outweigh the cost. The specialty diisocyanates also impart unique characteristics. For example, TODI and PPDI are used to produce TPUs with excellent set and hysteresis performance at elevated temperatures. These polymers are used in high end performance applications such as seals and gaskets. The high resilient non-softening Tecobax TPUs are based on the aliphatic isocyanates family. These materials have been made in polyester, polyether and polycarbonate versions. The properties of Tecobax based materials used to show the uniqueness of this type of TPU were determined by shore rebound and softening flexural modulus characteristics. The physical properties were also measured and compared to typical TPUs. A challenge in developing these materials was to make a material with acceptable extrusion quality. The extrusion quality films passed the internal quality system based on the TAPPI Dirt Estimation Chart T564. Normal highly resilient TPUs have a draw back in that the materials can be injection molded but have significant issues in being extruded into tubing with thin walls. The hard segments of these materials are highly organized/crystalline making them difficult to melt properly required to produce good extrusion quality thin films. Manipulating the hard segment by a novel process has resulted in a TPU that does not soften like similar TPUs while maintaining the extrusion quality of a typical thermoplastic polyurethane. Steam sterilization is typically not feasible with traditional aliphatic resins which have Vicat temperature between 35 C and 60 C; these materials melt at autoclave temperatures. Aromatic resins have higher Vicat softening temperature, between 60 C and 140 C, but Lubrizol cannot recommend steam sterilization for aromatic TPUs because of the possibility of the formation of methylene dianiline (MDA). The thermal characteristics of some Tecobax however, may allow the materials to be steam sterilized. The Vicat softening temperature of Tecobax TB-25D is 64 C which explains why the TB-25D melted during the autoclave cycle. However, TB-40D and TB-45D have Vicat temperature of 108 C and 136 C respectively. Tecobax may be found to be useful in a number of new medical device applications. Their compatibility with steam sterilization suggests they could be useful in medical packaging, reusable endoscopic devices, or orthopedic surgical guides. Their non-softening characteristics suggest they could be useful in percutaneous interventional catheters where torqueability and trackability are useful. Examples include epidural catheters and coronary guide catheters. Their high extrusion quality could make them attractive as balloon materials for percutaneous transluminal angioplasty catheters. Additional applications research is ongoing at Lubrizol LifeSciences to further explore the capabilities of these new TPUs and determine in what medical devices these unique materials could fill unmet needs. Conclusions Tecobax represents a new class of nonsoftening thermoplastic polyurethanes. The three grades that are commercially available, 25, 40, and 45D, have resiliency greater than the typical commercially available TPUs. They exhibit nonsoftening characteristics that are generally atypical of TPUs and more consistent with other medical grade copolyamides. The higher durometers are compatible with steam sterilization methods which is unique for aliphatic TPUs. They offer excellent thermal processibility and produce high clarity extruded film and tube. Even with the addition of these unique characteristics, this new class of TPU maintains the properties, e.g. abrasion resistance and strength that has made TPUs so attractive to SPE ANTEC Anaheim 2017 / 1891

8 medical device design engineers. This new class of TPU will broaden the design space for engineers using TPUs within and outside the medical device field of use. Acknowledgements The authors would like to acknowledge the following for help bring Tecobax from a concept to a product: Bryce Steinmetz, Pallavi Kulkarni, Elvin Rodriguez, Carl Ohlson, Shawn Lankowski and Gil Montague. References 1. M.D. Lelah, S.L. Cooper, Polyurethanes in Medicine, CRC Press Boca Raton, (1986). 2. Zdrahala R J, et.al. Journal of biomaterials applications (1988), 2, (4), Walder and D. Meltzer; Thermoplastic Polyurethanes: The Other TPE, Antec 2008, pp Limei, Lu; 8th Thermoplastic Elastomers Topical Conference 2007, TPE TopCon, pp Pinchuk; Leonard. US Patent 5,133,742 July 28, 1992 Crack-resistant polycarbonate urethane polymer prostheses 6. Tecobax, Tecoflex, Tecothane, and Carbothane are trademarks of The Lubrizol Corporation 7. Salazar M. et al. J. of Poly. Sci. Part B. Poly. Physics 2002, 40, Walder, A.J. Makal, U. Kulkarni, P. ANTEC Cincinnati 2014 SPE ANTEC Anaheim 2017 / 1892