Bio-based medical grade thermoplastic polyurethane elastomers, methods of making and use thereof

Abstract

This invention discloses a bio-based medical-grade thermoplastic polyurethane elastomer, its preparation method, and its applications, belonging to the field of medical polymer materials technology. The elastomer uses bio-based polytrimethylene carbonate diol as the soft segment, bio-based 1,5-pentanediisocyanate as the hard segment matrix, and bio-based 1,4-butanediol as the chain extender. It is prepared using a medical-grade tin-free catalyst composed of bismuth isooctanoate / bismuth neodecanoate, through a complete process of prepolymerization-twin-screw continuous chain extension-multi-stage vacuum devolatilization-gradient annealing. The bio-based medical-grade TPU prepared by this invention has a bio-based content of ≥88%, a residual isocyanate monomer content of <5ppm, and a total extractable content that meets the requirements of ISO10993-12 implantable materials. The material has an adjustable Shore hardness of 75A~90A, a tensile strength of ≥35MPa, and an elongation at break of ≥450%. After immersion in simulated body fluid at 37℃ for 180 days, the tensile strength retention rate is ≥85%, the cytotoxicity is grade 0, the hemolysis rate is <2%, and the mechanical properties decrease by <5% after gamma ray sterilization.

Description

Technical Field

[0001] This invention belongs to the field of medical polymer materials technology, specifically relating to a bio-based medical-grade thermoplastic polyurethane elastomer (TPU) and its preparation method, as well as the application of this material in medium- and long-term implantable medical devices. Background Technology

[0002] Thermoplastic polyurethane elastomer (TPU) is a block copolymer composed of alternating hard and soft segments. It combines the high elasticity of rubber with the heat processability of plastic. With its excellent biocompatibility, flexural strength, abrasion resistance and sterilizability, it has become one of the core basic materials in the field of high-end medical devices and is widely used in products such as interventional catheters, artificial blood vessels, cardiac occluders, and implantable drug delivery devices.

[0003] Currently, almost all commercially available medical-grade TPUs are synthesized from petroleum-based raw materials, such as petroleum-based polycarbonate diols and polytetrahydrofuran ether diols as soft segments, and 4,4'-diphenylmethane diisocyanate (MDI) and hexamethylene diisocyanate (HDI) as hard segments. Their production process has a high carbon footprint, and the supply chain is significantly affected by fluctuations in international crude oil prices and geopolitical factors. Driven by the dual demands of green transformation in the global healthcare industry and self-sufficiency in the supply chain, the development of bio-based medical-grade TPUs has become an important direction for industry development.

[0004] Existing bio-based TPU technology suffers from three main technical shortcomings, making it difficult to meet the stringent requirements of implantable medical devices: First, the performance and purity of bio-based systems are insufficient. Existing bio-based TPUs mostly use bio-based polyols such as castor oil, polylactic acid, and polycaprolactone as soft segments, combined with some bio-based isocyanates. The bio-based content of these materials is generally below 60%, and the polyester-type soft segments are prone to hydrolytic breakage under physiological conditions in vivo. Mechanical properties degrade by more than 30% after 3 months of implantation, failing to meet the clinical needs for medium- to long-term implantation (≥6 months). Simultaneously, bio-based raw materials are mostly prepared via bio-fermentation, resulting in complex impurities. Existing purification processes struggle to achieve the required purity of over 99.99% for medical-grade monomers, leading to excessive extractables in the final material and preventing it from passing ISO 10993 series biocompatibility certifications.

[0005] Second, the catalytic system poses potential biosafety risks. Current TPU synthesis commonly employs organotin catalysts (such as dibutyltin dilaurate), which offer high catalytic efficiency but exhibit some cytotoxicity. Furthermore, the heavy metal tin can easily remain in the material, posing potential health risks with long-term implantation. Although some studies have attempted to replace organotin catalysts with organobismuth catalysts, for the reaction system of bio-based polycarbonate diols and bio-based aliphatic isocyanates, single bismuth catalysts suffer from poor reaction selectivity and insufficient post-curing, easily leading to increased oligomer content and poor batch stability in the material.

[0006] Third, the manufacturing process does not meet the requirements for medical-grade mass production. Existing bio-based TPUs are mostly polymerized using one-step or batch methods in the laboratory, resulting in poor reaction uniformity, a wide molecular weight distribution, and a lack of targeted residual monomer removal and post-processing techniques. Implantable TPUs require residual isocyanate monomers below 5 ppm and total extractables below medical limits, while existing bio-based TPUs generally have residual monomers above 20 ppm and oligomer content exceeding 1%, failing to meet the compliance requirements for implantable materials. Furthermore, bio-based TPUs prepared using existing processes are prone to molecular chain degradation after gamma-ray sterilization, resulting in a mechanical property degradation exceeding 10%, making them unsuitable for the routine sterilization procedures of medical devices.

[0007] In summary, developing a bio-based TPU material with high bio-based content, high purity, resistance to in vivo hydrolysis, and compliance with implantable medical standards, along with its mass production preparation process, is a technical problem that urgently needs to be solved in the field of medical biomaterials. Summary of the Invention

[0008] The purpose of this invention is to address the shortcomings of existing technologies by providing a bio-based medical-grade thermoplastic polyurethane elastomer, its preparation method, and its application. This invention solves the technical problems of insufficient biosafety, poor hydrolysis resistance, and inability to meet medium- and long-term implantation medical standards of existing bio-based TPUs, thereby achieving a balance between high bio-based content and implantation-grade medical performance.

[0009] To address the problems existing in the prior art, the present invention provides a bio-based medical-grade thermoplastic polyurethane elastomer, which is prepared by polymerization of the following raw material components, in molar parts: Bio-based polycarbonate diol: 1 part; Bio-based aliphatic diisocyanate: 3.0~4.5 parts; Bio-based small molecule chain extender: 2.0~3.5 parts; Medical-grade composite bismuth catalyst: accounting for 0.005%~0.02% of the total raw material mass; Bio-based capping agent: accounting for 0.1%~0.3% of the total raw material mass; Medical-grade antioxidants: accounting for 0.1%~0.5% of the total raw material mass; The bio-based polycarbonate diol is bio-based polytrimethylene carbonate diol (BIO-PTMC) with a number-average molecular weight of 1000~3000 g / mol; the bio-based aliphatic diisocyanate is bio-based 1,5-pentanediisocyanate (BIO-PDI); and the bio-based small molecule chain extender is bio-based 1,4-butanediol (BIO-BDO).

[0010] Optionally, in the bio-based medical-grade thermoplastic polyurethane elastomer, the medical-grade composite bismuth catalyst is obtained by compounding bismuth isooctanoate and bismuth neodecanoate at a mass ratio of 1:1.5~2.5, and is completely free of heavy metals such as tin, mercury, and lead; the bio-based end-capping agent is bio-based n-octanol, used to end the active isocyanate groups at the ends of the molecular chains, reducing the risk of material precipitation; the medical-grade antioxidant is pentaerythritol tetrakis[β-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate] (antioxidant 1010, medical grade), used to improve the thermal stability and radiation sterilization resistance of the material.

[0011] Optionally, in the bio-based medical-grade thermoplastic polyurethane elastomer, the bio-based polytrimethylene carbonate diol is prepared by transesterification polycondensation of bio-based 1,3-propanediol and dimethyl carbonate, with a bio-based carbon content ≥95%; the bio-based 1,5-pentanediisocyanate is prepared by decarboxylation and phosgenation of bio-based lysine, with a bio-based carbon content ≥99%; and the bio-based 1,4-butanediol is prepared by hydrogenation of bio-based succinic acid, with a bio-based carbon content ≥99%.

[0012] Optionally, in the bio-based medical-grade thermoplastic polyurethane elastomer, the bio-based mass content of the elastomer is ≥88%, the residual 1,5-pentanediisocyanate monomer content is <5ppm, the Shore hardness is 75A~90A, the tensile strength is ≥35MPa, and the elongation at break is ≥450%.

[0013] This invention also provides a method for preparing a bio-based medical-grade thermoplastic polyurethane elastomer, comprising the following steps: Step S1: Raw material pretreatment: Bio-based polytrimethylene carbonate glycol was added to a dehydration reactor, and then vacuum dehydrated at 110-120℃ and an absolute pressure of <100Pa for 2-3 hours. After the moisture content was determined to be <50ppm by Karl Fischer method, the product was discharged for later use. Bio-based 1,5-pentanediisocyanate and bio-based 1,4-butanediol were purified by precision vacuum distillation. After the purity was determined to be ≥99.99% by gas chromatography, they were sealed and stored in a nitrogen-protected raw material tank. Step S2: Prepolymer preparation: In a stainless steel reactor equipped with stirring, temperature control, and nitrogen protection, dehydrated bio-based polytrimethylene carbonate diol is added, and nitrogen purging is initiated for 10 minutes to remove air. The temperature is raised to 70-80°C, and all bio-based 1,5-pentanediisocyanate is added at a uniform rate using a metering pump, with the stirring speed controlled at 80-120 rpm. After the addition is completed, the reaction is maintained at this temperature for 60-90 minutes. Samples are taken every 20 minutes, and the NCO value is determined by di-n-butylamine titration. When the measured NCO mass fraction reaches 3.5%-5.0% and the deviation from the theoretical value is ≤0.1%, the reaction is stopped, yielding an isocyanate-terminated prepolymer. Step S3: Continuous chain extension reaction: The prepolymer is heated to 85-95℃, and medical-grade composite bismuth catalyst, bio-based end-capping agent, and bio-based 1,4-butanediol preheated to 80℃ are added sequentially. After high-speed stirring for 30-60 seconds to mix evenly, the mixture is immediately fed into a twin-screw reactive extruder for continuous chain extension reaction. The temperatures of each section of the twin-screw extruder along the material direction are 120℃, 140℃, 160℃, 170℃, 180℃, 175℃, 165℃, and 150℃, respectively. The screw speed is 150-250 rpm, and the material residence time is 3-5 minutes. The system temperature before entering the twin-screw extruder is controlled at 90±5℃, and the viscosity is controlled at 800~1500 mPa. s, to ensure the chain extension reaction proceeds uniformly and avoid localized explosive polymerization. Step S4: Granulation and Crude Product Collection: The molten material extruded by twin screw extruders is cooled and shaped in a medical-grade deionized water bath at 20-25℃, and then fed into a cantilever pelletizer to obtain TPU coarse pellets with a diameter of 2-3mm and a length of 3-4mm; the deionized water used in the cooling bath has a resistivity ≥18.2MΩ. cm, to avoid introducing impurities; Step S5: Multi-stage vacuum devolatilization purification: TPU coarse particles are added to a vacuum devolatilization reactor equipped with a stirrer, and vacuum devolatilization is carried out in three stages with gradient heating: First stage: Temperature 100℃, absolute pressure <100Pa, stirring speed 20rpm, treatment for 6h, to remove most of the volatile residual monomers; Second stage: Temperature 110℃, absolute pressure <50Pa, stirring speed 30rpm, treatment for 8h, to remove bound residual monomers and small molecule oligomers; Third stage: Temperature 120℃, absolute pressure <30Pa, stirring speed 30rpm, treatment for 4~10h, deep removal of trace residues and oligomers; After devolatilization, the material is discharged at 60°C under nitrogen protection to obtain purified TPU granules. The mass percentage of oligomers with a molecular weight of less than 1000 is <0.2%, and the residual PDI monomer is <5ppm. Step S6: Post-processing after gradient annealing: The devolatilized TPU granules were spread evenly on a stainless steel tray and placed in a Class 1000 cleanroom hot air circulating oven for gradient annealing. First stage: Keep warm at 80℃ for 4 hours to promote the complete crystallization of hard segments; Second stage: Heat to 100℃ and hold for 2 hours to eliminate internal stress and stabilize the phase separation structure; Third stage: Cool down to 60℃ and keep warm for 2 hours to slowly release thermal stress; Finally, the oven was turned off and allowed to cool naturally to room temperature to obtain the finished bio-based medical-grade thermoplastic polyurethane elastomer.

[0014] Optionally, in the preparation method, in step S2, the NCO value is sampled and detected every 20 minutes during the prepolymer reaction. When the measured NCO value deviates from the theoretical NCO value by ≤0.1%, the reaction is stopped and the next step is initiated.

[0015] Optionally, in the preparation method, in step S3, the temperature of the mixture of prepolymer and chain extender before entering the twin-screw extruder is controlled at 90±5℃, and the viscosity of the system is controlled at 800~1500mPa. s.

[0016] Optionally, in the preparation method, after step S5 is completed, the mass percentage of oligomers with a molecular weight of less than 1000 in the TPU coarse granules is <0.2%.

[0017] This invention also provides an application of a bio-based medical-grade thermoplastic polyurethane elastomer, which is used to prepare medium- and long-term implantable medical devices, including cardiac occluder covers, artificial blood vessels, interventional catheters, implantable drug delivery pump assemblies, and neurointerventional microcatheters. It has excellent biocompatibility, resistance to in vivo aging, and sustainability, and solves the technical bottleneck that existing bio-based TPUs cannot meet implantable medical standards.

[0018] Optionally, in the application, the elastomer is processed into medical device parts by extrusion molding, injection molding, electrospinning or 3D printing. Before processing, it needs to be vacuum dried at 80°C for 4-6 hours to control the moisture content to <30ppm, so as to avoid bubbles or hydrolytic degradation during processing.

[0019] Compared with the prior art, the present invention has the following advantages: (1) Fully bio-based system with high sustainability: This invention is the first to use bio-based polytrimethylene carbonate diol, bio-based 1,5-pentanediisocyanate, and bio-based 1,4-butanediol to construct a fully bio-based TPU molecular chain. The overall bio-based mass content of the material is ≥88%, which reduces the carbon footprint by more than 60% compared with traditional petroleum-based medical TPU. This aligns with the global trend of green transformation in the medical device industry and reduces dependence on the petroleum supply chain.

[0020] (2) Implantable biosafety and outstanding compliance: This invention uses a medical-grade composite bismuth catalyst to completely replace organotin, eliminating the risk of heavy metal residues. Combined with precision distillation purification and multi-stage vacuum devolatilization processes, residual isocyanate monomers are controlled to below 5 ppm, oligomer content is <0.2%, and the total extractables are far below the limits of ISO10993-12. The material has a cytotoxicity level of 0, a hemolysis rate of <2%, and no significant difference in clotting time compared to the negative control, fully meeting the biosafety requirements for medium- and long-term implantable materials.

[0021] (3) Excellent resistance to in vivo aging: This invention employs polycarbonate soft segments combined with aliphatic PDI hard segments. The steric hindrance around the urethane bonds in the molecular chain is moderate, and the hard segments are densely crystalline, effectively blocking the erosion of water molecules and oxygen free radicals. After immersion in simulated body fluid (PBS buffer with pH=7.4) at 37℃ for 180 days, the tensile strength retention rate is ≥85%, and the mass loss rate is <1.5%, which is significantly better than existing polyester-based bio-based TPU and can meet the medium- to long-term implantation clinical needs of 6 to 12 months.

[0022] (4) Stable processing and sterilization compatibility: This invention utilizes a twin-screw continuous chain extender + gradient annealing process to achieve a narrow molecular weight distribution (PDI≤1.8) and batch-to-batch mechanical property deviation <3%, making it stably compatible with high-end processing technologies such as precision extrusion and thin-wall injection molding. After sterilization with 25kGy gamma rays, the tensile strength decreases by <5%, and the yellowness index changes by <2, making it suitable for routine sterilization processes in medical devices without significant aging, discoloration, or performance degradation.

[0023] (5) The mass production process is mature and the industrialization feasibility is strong: The preparation process of this invention is based on mature industrial-grade twin-screw reactive extrusion and vacuum devolatilization equipment, which can achieve continuous mass production, with a single production line having an annual capacity of thousands of tons; the process parameters are highly controllable, the product batches are highly stable, and it meets the production quality management standards for medical-grade materials, thus possessing the conditions for rapid industrialization. Detailed Implementation

[0024] The specific embodiments of the present invention will now be described in more detail. The advantages and features of the present invention will become clearer from the following description.

[0025] In the following, if the methods described herein include a series of steps, the order of these steps presented herein is not necessarily the only order in which these steps can be performed, and some of the steps described may be omitted and / or some other steps not described herein may be added to the method.

[0026] I. Description of Experimental Materials: The main raw materials used in the examples and comparative examples are as follows: Bio-based polytrimethylene carbonate diol (BIO-PTMC): number average molecular weight 1000, 2000, 3000 g / mol, bio-based carbon content 96%, custom grade from Yuanli Chemical Group Co., Ltd. Bio-based 1,5-pentanediisocyanate (BIO-PDI): 99.5% purity (crude product), purified to 99.99% by laboratory distillation, Anhui Fengyuan Group Co., Ltd. Bio-based 1,4-butanediol (BIO-BDO): 99.7% purity (crude product), purified to 99.99% by distillation, with a bio-based carbon content of 99%, produced by Shanxi Meijin Energy Co., Ltd. Petroleum-based hexamethylene diisocyanate (HDI): Industrial grade, 99.5% purity, Wanhua Chemical Group Co., Ltd. Petroleum-based polybutylene adipate diol (PBA): Number average molecular weight 2000 g / mol, industrial grade, Shandong Lanxing Dongda Co., Ltd. Bismuth isooctanoate: Medical grade, 20% bismuth content, Guangzhou Yourun Synthetic Materials Co., Ltd. Bismuth neodecanoate: Medical grade, bismuth content 20%, Guangzhou Yourun Synthetic Materials Co., Ltd.; Dibutyltin dilaurate (T-12): Industrial grade, Air Products, Inc., USA; Bio-based n-octanol: Medical grade, 99.9% purity, 99% bio-based carbon content, KLK Company, Malaysia; Antioxidant 1010: Medical grade, BASF AG.

[0027] II. Example 1: This embodiment prepares a bio-based medical-grade TPU with the following raw material molar ratios: 1 mol of BIO-PTMC (2000 g / mol), 3.5 mol of BIO-PDI, and 2.5 mol of BIO-BDO; a composite catalyst (bismuth isooctanoate: bismuth neodecanoate = 1:2) accounts for 0.01% of the total mass, bio-based n-octanol accounts for 0.2% of the total mass, and antioxidant 1010 accounts for 0.3% of the total mass.

[0028] The preparation steps are as follows: Raw material pretreatment: BIO-PTMC (2000) was dehydrated under vacuum at 115℃ and 80Pa absolute pressure for 2.5h, and the moisture content was measured to be 38ppm; BIO-PDI and BIO-BDO were purified by vacuum distillation, and the purity was detected by gas chromatography to be 99.992% and 99.995%, respectively.

[0029] Prepolymer preparation: 1 mol of dehydrated BIO-PTMC was added to the reactor, and after purging with nitrogen, the temperature was raised to 75℃. 3.5 mol of BIO-PDI was added at a uniform rate, and the mixture was stirred at 100 rpm for 75 min. The NCO mass fraction was measured and found to be 4.2%, which was 0.08% lower than the theoretical value. The reaction was then stopped.

[0030] Continuous chain extension: The prepolymer is heated to 90°C, and the composite catalyst, end-capping agent and preheated BIO-BDO are added. After high-speed stirring for 45 seconds, it is fed into a twin-screw extruder. The temperature of each section of the twin screw is 120 / 140 / 160 / 170 / 180 / 175 / 165 / 150°C, the screw speed is 200 rpm, and the material residence time is 4 min.

[0031] Granulation: The extruded strip is cut into pellets after being cooled in a 23°C deionized water bath to obtain coarse pellets.

[0032] Multi-stage devolatilization: Coarse material is added to the devolatilization reactor and treated at 100℃ / 100Pa for 6 hours, 110℃ / 50Pa for 8 hours, and 120℃ / 30Pa for 6 hours; then cooled and discharged.

[0033] Gradient annealing: hold at 80℃ for 4 hours, at 100℃ for 2 hours, at 60℃ for 2 hours, and then cool naturally to obtain the finished product.

[0034] III. Example 2: The difference between this embodiment and Example 1 is that the number-average molecular weight of BIO-PTMC is 1000 g / mol, the amount of BIO-PDI is 4.2 mol, the amount of BIO-BDO is 3.2 mol, the amount of composite catalyst is 0.015%, and the remaining raw materials and process parameters are the same as in Example 1.

[0035] IV. Example 3: The difference between this embodiment and Example 1 is that the number-average molecular weight of BIO-PTMC is 3000 g / mol, the amount of BIO-PDI is 3.2 mol, the amount of BIO-BDO is 2.2 mol, the amount of composite catalyst is 0.008%, and the remaining raw materials and process parameters are the same as in Example 1.

[0036] V. Example 4: The difference between this embodiment and Example 1 is that the ratio of bismuth isooctanoate to bismuth neodecanoate in the composite catalyst is 1:1.5, and the dosage is 0.02%; the third stage of devolatilization treatment time is 10 hours, and the remaining raw materials and process parameters are the same as in Example 1.

[0037] VI. Example 5: The difference between this embodiment and Example 1 is that the ratio of bismuth isooctanoate to bismuth neodecanoate in the composite catalyst is 1:2.5, and the dosage is 0.005%; the third stage of devolatilization treatment time is 4 hours, and the remaining raw materials and process parameters are the same as in Example 1.

[0038] VII. Comparative Example 1: This comparative example is a petroleum-based medical TPU control, using petroleum-based HDI instead of BIO-PDI, petroleum-based polycarbonate diol (PCDL, 2000 g / mol) instead of BIO-PTMC, and petroleum-based BDO as a chain extender; the catalyst is dibutyltin dilaurate (T-12), with a dosage of 0.01%; no multi-stage vacuum devolatilization is performed, only ordinary drying treatment is performed; the remaining process parameters are the same as in Example 1.

[0039] 8. Comparative Example 2: This comparative example is a polyester-based bio-based TPU control, using bio-based polybutylene succinate diol (PBS diol, 2000 g / mol) instead of BIO-PTMC. The remaining raw materials and process parameters are the same as in Example 1.

[0040] IX. Comparative Example 3: This comparative example uses a single bismuth isooctanoate catalyst at a dosage of 0.01%, without multi-stage devolatilization and gradient annealing treatment, and the remaining raw materials and process parameters are the same as in Example 1.

[0041] 10. Performance Testing Methods and Results: (a) Testing methods: Bio-based content: The bio-based carbon content of the material was determined by radiocarbon dating using the ASTM D6866-22 method.

[0042] Mechanical properties: Dumbbell-shaped specimens were prepared according to GB / T 528-2009, and tensile strength and elongation at break were tested by a universal testing machine at a tensile rate of 500 mm / min; Shore hardness was tested according to GB / T 531.1-2008.

[0043] Residual monomer content: The content of free PDI / HDI monomers in the material was determined by high performance liquid chromatography (HPLC).

[0044] Hydrolysis resistance: The sample was immersed in PBS buffer at 37℃ and pH=7.4 for 180 days, then removed, dried and tested for tensile strength, and the strength retention rate was calculated.

[0045] Biocompatibility: Cytotoxicity: Tested according to GB / T 16886.5-2017 using the L929 cell extract method, graded from 0 to 4.

[0046] Hemolysis rate: tested according to GB / T 16886.4-2003.

[0047] Clotting time: Activated partial thromboplastin time (APTT) was used as the test.

[0048] Sterilization stability: After the sample was sterilized by irradiation with 25 kGy gamma rays, the changes in tensile strength and yellowness index were tested.

[0049] Total extractables: The total amount of non-volatiles was determined by extraction with physiological saline and vegetable oil separately according to ISO 10993-12.

[0050] (II) Test Results: The performance test results of each embodiment and comparative example are shown in Table 1.

[0051] Table 1 Comparison of performance test results for each sample

[0052] Table 1:

[0053] (III) Results Analysis: Bio-based content: The bio-based content of Examples 1-5 is ≥88%, which is far higher than the level of existing commercial bio-based TPUs, realizing the medical-grade transformation of the entire bio-based system.

[0054] Mechanical properties: The tensile strength of the material of this invention can reach 35~42MPa, the elongation at break is 450%~580%, and the hardness is adjustable from 76A to 88A. The performance is comparable to that of petroleum-based medical TPU (Comparative Example 1), and meets the mechanical requirements of medical devices.

[0055] Residue and purity: The example controlled the residual monomers to within 5 ppm through a multi-stage devolatilization process, and the total amount of extractables was much lower than that of the comparative example, meeting the purity requirements of implantable materials; the comparative example 3 did not undergo devolatilization treatment, and the residual monomers were as high as 21.5 ppm, which could not meet the medical standards.

[0056] Hydrolysis resistance: The polycarbonate-based bio-based TPU of this invention retains ≥85% of its strength after 180 days of hydrolysis, which is comparable to petroleum-based PCL-based TPU and significantly better than polyester-based bio-based TPU (comparative Example 2: only 62.3%), proving that the material of this invention is suitable for medium- and long-term implantation scenarios.

[0057] Biocompatibility: The materials of this invention have a cytotoxicity of grade 0 and a hemolysis rate of <2%, which is superior to the petroleum-based materials catalyzed by organotin (Comparative Example 1) and the unpurified materials (Comparative Example 3), demonstrating excellent biocompatibility.

[0058] Sterilization stability: The strength of the material of this invention decreases by less than 5% after gamma sterilization, and the yellowness changes little, which is significantly better than the comparative example and can be adapted to the sterilization process of conventional medical devices.

[0059] XI. Application Verification Example: Using the bio-based medical-grade TPU prepared in Example 1, interventional catheter samples with a wall thickness of 0.2 mm and an outer diameter of 3 mm were prepared by precision extrusion; at the same time, a porous membrane with a thickness of 0.1 mm was prepared by electrospinning for use as a cardiac occluder simulation sample.

[0060] Test results showed that the extruded catheter had a dimensional accuracy of ±0.01 mm, a smooth and defect-free inner wall, and a burst pressure ≥1200 psi, meeting the mechanical requirements of interventional catheters. The electrospun coating had an adjustable pore size of 10~30 μm and a porosity ≥70%. Cell seeding experiments showed good endothelial cell adhesion and proliferation with no obvious inflammatory response. The above samples showed no significant change in performance after ethylene oxide sterilization, verifying the feasibility of the material of this invention in implantable medical devices.

Claims

1. A bio-based medical-grade thermoplastic polyurethane elastomer, characterized in that, The bio-based medical-grade thermoplastic polyurethane elastomer is prepared by polymerization of the following raw material components, in molar parts: Bio-based polycarbonate diol: 1 part; Bio-based aliphatic diisocyanate: 3.0~4.5 parts; Bio-based small molecule chain extender: 2.0~3.5 parts; Medical-grade composite bismuth catalyst: accounting for 0.005%~0.02% of the total raw material mass; Bio-based capping agent: accounting for 0.1%~0.3% of the total raw material mass; Medical-grade antioxidants: accounting for 0.1%~0.5% of the total raw material mass; The bio-based polycarbonate diol is bio-based polytrimethylene carbonate diol with a number-average molecular weight of 1000~3000 g / mol; the bio-based aliphatic diisocyanate is bio-based 1,5-pentanediisocyanate; and the bio-based small molecule chain extender is bio-based 1,4-butanediol.

2. The bio-based medical-grade thermoplastic polyurethane elastomer according to claim 1, characterized in that, The medical-grade composite bismuth catalyst is obtained by compounding bismuth isooctanoate and bismuth neodecanoate at a mass ratio of 1:1.5~2.5; the bio-based end-capping agent is bio-based n-octanol; and the medical-grade antioxidant is pentaerythritol tetrakis[β-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate].

3. The bio-based medical-grade thermoplastic polyurethane elastomer according to claim 1, characterized in that, The bio-based polytrimethylene carbonate diol is prepared by transesterification polycondensation of bio-based 1,3-propanediol and dimethyl carbonate, with a bio-based carbon content ≥95%; the bio-based 1,5-pentanediisocyanate is prepared by decarboxylation and phosgenation of bio-based lysine, with a bio-based carbon content ≥99%; the bio-based 1,4-butanediol is prepared by hydrogenation of bio-based succinic acid, with a bio-based carbon content ≥99%.

4. The bio-based medical-grade thermoplastic polyurethane elastomer according to claim 1, characterized in that, The elastomer has a bio-based mass content of ≥88%, a residual 1,5-pentanediisocyanate monomer content of <5ppm, a Shore hardness of 75A~90A, a tensile strength of ≥35MPa, and an elongation at break of ≥450%.

5. A method for preparing a bio-based medical-grade thermoplastic polyurethane elastomer as described in any one of claims 1 to 4, characterized in that, Includes the following steps: Step S1: Raw material pretreatment: Bio-based polytrimethylene carbonate diol was vacuum dehydrated at 110-120℃ and an absolute pressure of <100Pa for 2-3 hours to control the moisture content to <50ppm; bio-based 1,5-pentanediisocyanate and bio-based 1,4-butanediol were purified by vacuum distillation to control the purity to ≥99.99%. Step S2: Prepolymer preparation: Dehydrated bio-based polytrimethylene carbonate diol was added to a nitrogen-protected reactor, the temperature was raised to 70-80℃, all bio-based 1,5-pentanediisocyanate was added, the stirring speed was controlled at 80-120 rpm, and the reaction was carried out for 60-90 min to obtain an isocyanate-terminated prepolymer with an NCO mass fraction of 3.5%-5.0%. Step S3: Continuous chain extension reaction: The prepolymer is heated to 85-95℃, and medical-grade composite bismuth catalyst, bio-based end-capping agent, and bio-based 1,4-butanediol preheated to 80℃ are added sequentially. After high-speed stirring for 30-60 seconds to mix evenly, the mixture is immediately fed into a twin-screw reactive extruder for continuous chain extension reaction. The temperatures of each section of the twin-screw extruder along the material direction are 120℃, 140℃, 160℃, 170℃, 180℃, 175℃, 165℃, and 150℃, respectively. The screw speed is 150-250 rpm, and the material residence time is 3-5 minutes. Step S4: Granulation and Crude Product Collection: The twin-screw extruded strips are cooled in a 20-25°C deionized water bath and then fed into a pelletizer to obtain TPU coarse pellets. Step S5: Multi-stage vacuum devolatilization purification: TPU coarse particles are added to a vacuum devolatilization reactor and devolatilization is carried out in three stages: the first stage temperature is 100℃ and the absolute pressure is <100Pa, and the treatment is 6h; the second stage temperature is 110℃ and the absolute pressure is <50Pa, and the treatment is 8h; the third stage temperature is 120℃ and the absolute pressure is <30Pa, and the treatment is 4~10h; after the devolatilization is completed, the temperature is reduced to 60℃ and the material is discharged. Step S6: Post-processing after gradient annealing: The devolatilized TPU granules were placed in a hot air circulating oven and kept at 80°C for 4 hours. Then the temperature was raised to 100°C and kept for 2 hours. After that, the temperature was lowered to 60°C and kept for 2 hours. Finally, the temperature was allowed to cool naturally to room temperature to obtain the finished bio-based medical-grade thermoplastic polyurethane elastomer.

6. The preparation method according to claim 5, characterized in that, In step S2, the NCO value is sampled and tested every 20 minutes during the prepolymer reaction. When the measured NCO value deviates from the theoretical NCO value by ≤0.1%, the reaction is stopped and the next step is initiated.

7. The preparation method according to claim 5, characterized in that, In step S3, the temperature of the mixture of prepolymer and chain extender before entering the twin-screw extruder is controlled at 90±5℃, and the viscosity of the system is controlled at 800~1500mPa. s.

8. The preparation method according to claim 5, characterized in that, After step S5 is completed, the mass percentage of oligomers with a molecular weight of less than 1000 in the TPU coarse granules is less than 0.2%.

9. An application of the bio-based medical-grade thermoplastic polyurethane elastomer as described in any one of claims 1 to 4, characterized in that, The elastomer is used to prepare medium- and long-term implantable medical devices, which include cardiac occluder covers, artificial blood vessels, interventional catheters, implantable drug delivery pump assemblies, and neurointerventional microcatheters.

10. The application according to claim 9, characterized in that, The elastomer is processed into medical device parts by extrusion molding, injection molding, electrospinning or 3D printing. Before processing, it needs to be vacuum dried at 80℃ for 4~6 hours to control the moisture content <30ppm.

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