Anti-calcification hemocompatible fatigue-resistant multiple silicon integrated polyurethane, and preparation method and application thereof

Abstract

The application provides an anti-calcification blood compatible fatigue-resistant multi-silicon integrated polyurethane and a preparation method and application thereof, and belongs to the field of biomedical materials. The polyurethane uses hydroxyl-terminated polycarbonate (PCDL) and polydimethylsiloxane (PMDS) as soft segments, and is polymerized with diisocyanate to prepare a prepolymer, 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane is selected for preliminary chain extension to introduce a silane structure into the soft segment of the polyurethane, then 3,9-bis(1,1-dimethyl-2-hydroxyethyl)-2,4,8,10-oxospiro is used for secondary chain extension, and beta-cyclodextrin is added for end capping to prepare the polyurethane elastomer. The polyurethane elastomer prepared by the above method has excellent biocompatibility, blood compatibility and anti-calcification. The mechanical property of the polyurethane elastomer is adjustable, fatigue-resistant, creep-resistant and good in shear resistance. The prepared polyurethane molecule is easy to be compounded and modified. The polyurethane is thermoplastic, and can be used for constructing in-vivo implants with specific requirements in different processing modes.

Description

TECHNICAL FIELD

[0001] The application provides an anti-calcification blood compatible fatigue-resistant multi-silicon integrated polyurethane and a preparation method and application thereof, and belongs to the field of biomedical materials. By regulating the distribution of silane in the molecular structure, the anti-calcification ability and blood compatibility of the polyurethane can be realized, and the material has mechanical stability and biocompatibility under long-term use. BACKGROUND

[0002] With the rapid development of medical technology, the demand for high-performance biomaterials is increasing. Especially in the field of in vivo implants, higher requirements are put forward for the stability of materials under long-term use. Polyurethane, as a multifunctional polymer material, is widely used in the medical field due to its excellent mechanical properties, processing convenience and good biocompatibility. However, traditional polyurethane materials may encounter problems such as degradation of mechanical properties, reduction of biocompatibility and insufficient anti-calcification ability during long-term use, which limits their application in high-end medical implants.

[0003] Silane-based materials are generally considered to have good biocompatibility of implants, but such materials are usually difficult to withstand long-term use due to poor mechanical properties. In addition, considering the adaptation to more severe microenvironments, the blood compatibility and anti-calcification ability of the material are more stringent. In the past, the ability was usually improved by surface modification, but under the requirement of long-term use, performance degradation, serious induction of tissue degenerative diseases in the body and even the risk of secondary surgery often occur. How to regulate the structure of polyurethane to obtain the stability of long-term in vivo implantation has become the key to material design.

[0004] The flexible molecular structure of polyurethane provides the possibility for structure design under different environments. By introducing silane segments into polyurethane, the biocompatibility can be improved. However, due to the lack of obvious intermolecular interaction between silanes, the mechanical properties of the material are lost. In order to solve this problem, by regulating the composition of the chain extender and crosslinking agent as the hard segment in polyurethane, the intermolecular interaction mode can be effectively regulated to meet the demand for mechanical properties of polyurethane under different environments. However, in order to realize the good secondary processing ability of polyurethane, the polyurethane needs to be designed as a thermoplastic polyurethane without crosslinking or with low crosslinking degree, which further increases the demand for polyurethane structure design.

[0005] In this context, the present invention aims to improve the biocompatibility, anti-calcification ability and hemocompatibility of polyurethane materials by introducing multiple silane structures, while maintaining their mechanical stability under long-term use. In addition, the thermoplastic polyurethane elastomer developed by the present invention can be processed flexibly to meet the specific needs of material performance for different medical applications, to adapt to different medical device and implant designs. SUMMARY

[0006] The first object of the present invention is to provide an anti-calcification hemocompatible fatigue-resistant multiple silicon integrated polyurethane, which uses hydroxyl-terminated polycarbonate (PCDL) and polydimethylsiloxane (PMDS) as soft segments together, and diisocyanate to prepare a prepolymer. 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane is selected for primary chain extension to introduce silane structures in the soft segment of polyurethane, and then 3,9-bis(1,1-dimethyl-2-hydroxyethyl)-2,4,8,10-oxaspiro is used for secondary chain extension, and finally the polyurethane elastomer is synthesized by β-cyclodextrin capping according to the demand of mechanical properties.

[0007] Among them, polydimethylsiloxane and 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane are introduced at the same time to uniformly integrate silane segments in polyurethane, thereby regulating the adaptability to the microenvironment. Further, 3,9-bis(1,1-dimethyl-2-hydroxyethyl)-2,4,8,10-oxaspiro is used as a chain extender to achieve continuous regeneration of hydrogen bonds between polyurethane molecules, for obtaining an elastomer with good mechanical stability. The β-cyclodextrin is used to improve the hydrophilicity and achieve modification through host-guest interaction. The polyurethane synthesized by this method has thermoplasticity and can be used for material processing through repeated dissolution; the viscosity of the polyurethane during solvent processing can also be regulated by organic solvents. This polyurethane structure is stable and will not cause mechanical property loss due to repeated processing.

[0008] The above-mentioned polyurethane is characterized in that the polyurethane elastomer uniformly integrated with silane has good biocompatibility, and can adapt to different microenvironments such as blood, bile, gastric juice, urine, and tissue fluid. The polyurethane has mechanical stability, including fatigue resistance, creep resistance, shear resistance, tear resistance, and can also be used to maintain stable hemodynamics. The polyurethane has the ability to be secondarily modified through host-guest interaction, and can be applied to drug loading, structure compounding, interface connection, molecular recognition, and substance detection. The polyurethane has thermoplasticity and can be processed into different shapes to meet the needs of different in-vivo implants, including artificial heart valves, heart patches, heart occluders, artificial blood vessels, vascular stents, vascular prostheses, balloon catheters, guide wires, spring coils, and other different medical devices.

[0009] The molecular structure of the polyurethane needs to be designed before preparation, including the following steps:

[0010] (1) Based on the elasticity of the target application scenario, calculate the molecular weight of PCDL and PMDS, and adjust the elastic modulus of polyurethane by controlling the molecular weight and degree of polymerization of the prepolymer. PCDL is used to increase the elastic modulus, while increasing the molecular weight of PDMS will reduce the elasticity. In order to maintain biocompatibility, the molar ratio of PCDL to PDMS is controlled at (1-4):1.

[0011] (2) Based on the application scenario's requirements for blood compatibility and anti-calcification ability, calculate the amount of 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane. The more 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane, the better the polyurethane's anti-adhesion ability. The amount of 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane needs to be always controlled to be no more than half of the total amount of chain extender to prevent a decrease in the material's mechanical properties.

[0012] (3) Adjust the amount of 3,9-bis(1,1-dimethyl-2-hydroxyethyl)-2,4,8,10-oxohelices according to the viscoelasticity requirements of the application scenario. The higher the frequency of deformation in the application environment of the material, the greater the amount of 3,9-bis(1,1-dimethyl-2-hydroxyethyl)-2,4,8,10-oxohelices, and the higher the tan δ of the polyurethane will be.

[0013] (4) Based on the fatigue resistance requirements of the application environment, the remaining isocyanate is cross-linked with cyclodextrin. The degree of cross-linking is adjusted according to the requirements of material toughness, but β-cyclodextrin is used to provide an average of 3 cross-linking points at most, otherwise it will affect the thermoplasticity of polyurethane.

[0014] A second objective of this invention is to provide a method for preparing the aforementioned anti-calcification, blood-compatible, fatigue-resistant multi-silicone integrated polyurethane, comprising the following steps:

[0015] (1) Add PCDL and PMDS to a three-necked flask and heat to a molten state to obtain a mixture. The purpose of heating to melt is to remove water. The purpose of removing water is to ensure precise control in the subsequent reaction process and to eliminate the side reaction between H2O and isocyanate.

[0016] (2) Cool the mixture obtained in (1) to 50-70℃, add hexamethylene diisocyanate and dibutyltin dilaurate catalyst, stir and react for 2-6 hours under nitrogen protection to obtain polyurethane prepolymer; during the reaction, the viscosity of the system needs to be controlled at the same level. The viscosity of the system can be controlled by adding dimethyl sulfoxide to ensure a stable reaction process.

[0017] (3) Add 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane as a chain extender to the polyurethane prepolymer obtained in (2) and react for 1-3 hours. The chain extender needs to be added drop by drop, and the stirring speed should be increased to 200 r / min to prevent the phenomenon of rapid and uneven polymerization caused by the reaction.

[0018] (4) Add 3,9-bis(1,1-dimethyl-2-hydroxyethyl)-2,4,8,10-oxohelices to the product obtained in (3) to continue chain extension, and react for 1-2 hours; 3,9-bis(1,1-dimethyl-2-hydroxyethyl)-2,4,8,10-oxohelices need to be dissolved in DMSO beforehand, and then the solution is added dropwise to the system.

[0019] (5) Add β-cyclodextrin as a crosslinking agent to the product obtained in (4) and react for 1-4 hours; β-cyclodextrin needs to be dried in advance and stored in a desiccator. Solid crosslinking agents need to be dissolved in DMSO beforehand, and then the solution is added dropwise to the system.

[0020] (6) Collect the product obtained in (5), dry it to remove the solvent, and obtain the final product;

[0021] (7) The product obtained in (6) is soaked in deionized water to remove small molecules, and then dried again to obtain medical polyurethane elastomer.

[0022] Preferably, in step (1), the molar ratio of PCDL to PDMS is (1-4):1.

[0023] Preferably, in step (2), the molar ratio of hexamethylene diisocyanate to (PCDL+PDMS) is 1:(2-2.5), where (PCDL+PDMS) is the total amount of macromolecules added in step (1). The molar ratio of dibutyltin dilaurate catalyst to hexamethylene diisocyanate is 0.01:1. The stirring speed is 60~100 r / min.

[0024] Preferably, in step (3), the molar ratio of 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane to (PCDL+PDMS) is 0.4:1.

[0025] Preferably, in step (4), the molar ratio of 3,9-bis(1,1-dimethyl-2-hydroxyethyl)-2,4,8,10-oxohelices to (PCDL+PDMS) is 0.4:1.

[0026] Preferably, in step (5), the molar ratio of β-cyclodextrin to (PCDL+PDMS) is 0.2:1.

[0027] Preferably, in step (6), the drying is carried out in a forced-air drying oven at 80°C.

[0028] Preferably, in step (7), the product obtained in (6) is soaked in deionized water for 5-10 days, with the water changed daily to ensure that all small molecules in the material are released. Then it is dried again.

[0029] Furthermore, PCDL and PDMS in step (1) can be replaced with other macromolecular diols. As long as the product has good biocompatibility, good reactivity, and good stability, one or more macromolecular diols can be used simultaneously, including but not limited to hydroxyl-terminated polycarbonate, hydroxyl-terminated polycaprolactone, poly(terephthalic anhydride-ethylene glycol), 1,4-cyclohexane polyester diol, polytetrahydrofuran, polyisosorbate diol, polyethylene glycol, etc.

[0030] Furthermore, hexamethylene diisocyanate in step (2) can be replaced with other diisocyanates. As long as the product has good biocompatibility, no biotoxicity, good reactivity, and good stability, one or more of the diisocyanates used can be used simultaneously, including but not limited to hexamethylene diisocyanate, lysine diisocyanate, 4,4'-dicyclohexylmethane diisocyanate, and isophorone diisocyanate.

[0031] Furthermore, the 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane in step (3) can be replaced with other chain extenders. As long as the chain extender used has good biocompatibility, no biotoxicity, good reactivity, and good stability, other small molecule substances can be introduced, including but not limited to 1,4-butanediol, 1,6-hexanediol, diethylene glycol, 1,4-cyclohexanediol, hexamethylenediamine, L-cysteine, arginine, dicumyl peroxide, and dimethylsilanediol.

[0032] Furthermore, the β-cyclodextrin in step (5) can be replaced with other crosslinking agents. The crosslinking agents used in the synthesis of polyurethane should have good biocompatibility, no biotoxicity, good reactivity, and good stability. One or more macrocyclic polyhydroxy compounds and their derivatives can be used simultaneously, including but not limited to hydroxypropyl β-cyclodextrin and calixarene.

[0033] A third objective of this invention is to provide applications of the polyurethane, including processing and molding it, including but not limited to casting, spraying, reaction injection molding, extrusion molding, compression molding, and variable fiber injection molding.

[0034] Furthermore, the casting process includes the following steps:

[0035] (1) Weigh the medical polyurethane elastomer prepared above, add it to the dimethyl sulfoxide solution and heat and stir until the elastomer is completely melted to obtain a 20-80 wt% polyurethane solution. The heating temperature is 80-120℃ and the stirring speed is 50 r / min. During the stirring process, condense and reflux to prevent DMSO loss.

[0036] (2) Add the polyurethane solution from (1) into the injection molding machine and inject it into the mold, or pour it directly into the mold to level and form a film.

[0037] (3) Place the polyurethane and mold at -20℃ for cold storage to set and demold, and then place them in a 60℃ forced-air drying oven to remove a large amount of organic solvent until the polyurethane shape is completely fixed.

[0038] (4) Soak the polyurethane material obtained in (3) in ionized water for 7 days, changing the water once a day to ensure that all small molecules in the material are released, and obtain the final product.

[0039] The polyurethane elastomer prepared using the method described above exhibits excellent biocompatibility, blood compatibility, and resistance to calcification. Its mechanical properties are tunable, and it demonstrates good fatigue resistance, creep resistance, and shear strength. The prepared polyurethane molecules are easily compounded and modified. Due to its thermoplasticity, polyurethane can be adapted to different processing methods for constructing implants with specific needs.

[0040] This invention presents a fatigue-resistant polyurethane material with long-term blood compatibility and anti-calcification capabilities. It features versatility in various forms and applications, ease of handling, good biocompatibility, and suitable mechanical properties. It can be used in the design of long-term implants for various complex internal environments, including artificial heart valves, heart patches, heart occluders, artificial blood vessels, vascular stents, vascular prostheses, balloon catheters, guidewires, and coils.

[0041] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0042] 1. This invention provides a polyurethane with multiple silane-introduced structures. This polyurethane incorporates polydimethylsiloxane into its soft segments, achieving good biocompatibility. The polyurethane's adaptability to different tissue microenvironments is regulated by 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane. The elastic modulus of this polyurethane is controlled by adjusting the proportion and molecular weight of the soft segments, and the intermolecular interactions are regulated by 3,9-bis(1,1-dimethyl-2-hydroxyethyl)-2,4,8,10-oxohelices. Good fatigue resistance is achieved through localized high-density hydrogen bonding.

[0043] 2. The polyurethane synthesized in this invention possesses host-guest recognition and inclusion capabilities, allowing it to be combined with other materials; it is thermoplastic, satisfying various processing modes; it meets the requirements for blood compatibility and anti-calcification capabilities for in vivo implantation; it allows for the regulation of viscoelasticity to meet deformation requirements at different frequencies; and it has good shear resistance, enabling suture implantation surgery. Attached Figure Description

[0044] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0045] Figure 1 The polyurethane of Embodiment 1 of the present invention 1 H NMR spectrum;

[0046] Figure 2 This is a DSC diagram of the polyurethane in Embodiment 1 of the present invention;

[0047] Figure 3 Blood compatibility test of polyurethane in Example 2 of the present invention;

[0048] Figure 4 This is the calcium deposition of polyurethane in simulated body fluid in Example 3 of the present invention. Detailed Implementation

[0049] To make the technical problems, technical solutions and advantages of the present invention clearer, a detailed description will be given below in conjunction with the accompanying drawings and specific embodiments.

[0050] Example 1

[0051] To meet the requirements for blood compatibility and anti-calcification capabilities, the molar ratio of 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane to 3,9-bis(1,1-dimethyl-2-hydroxyethyl)-2,4,8,10-oxohelix is ​​1:1. However, it is not cross-linked with β-cyclodextrin and is mainly used to prepare hydrophobic films, while also giving the films lower toughness. The preparation and processing method of the polyurethane with multiple introduced silane structures is as follows:

[0052] Weigh 8.0 g of hydroxyl-terminated polycarbonate 2000 and 0.5 g of hydroxyl-terminated polydimethylsiloxane 500 into a three-necked flask, heat at 110 °C for 30 min to remove moisture; cool to 60 °C, add 1.61 mL of hexamethylene diisocyanate and 1 drop of dibutyltin dilaurate catalyst, add dimethyl sulfoxide to adjust the viscosity of the system, stir the reaction under nitrogen protection for 3 h at a stirring speed of 100 r / min to obtain polyurethane prepolymer;

[0053] 0.69 mL of 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane was added to the polyurethane prepolymer, and the reaction was carried out for 1.5 h; then 0.76 g of 3,9-bis(1,1-dimethyl-2-hydroxyethyl)-2,4,8,10-oxohelicol was added, and the reaction was carried out for 2 h; the sample was collected and placed in an 80℃ forced-air drying oven to remove the solvent, thus obtaining the medical polyurethane material;

[0054] Weigh 2.0g of medical polyurethane material and add it to 6.0mL of dimethyl sulfoxide solution. Heat and stir at 100℃ and 100r / min. After the material is completely melted, pour the polyurethane solution into a polytetrafluoroethylene mold to level and form a film.

[0055] The film was then placed in a 60℃ forced-air drying oven for 24 hours, and then soaked in deionized water for 7 days, with the water changed once a day, to obtain a polyurethane film with good blood compatibility and anti-calcification ability.

[0056] Example 2

[0057] To achieve good toughness in the material, the crosslinking degree of the polyurethane is increased by β-cyclodextrin. To maintain the hydrophobicity of the polyurethane material, high molecular weight polydimethylsiloxane 1000 is used in the soft segment region to maintain the material's blood compatibility and anti-calcification ability. The preparation and processing method of the polyurethane with multiple silane structures is as follows:

[0058] Weigh 5.0 g of polytetrahydrofuran 2000 and 2.5 g of hydroxyl-terminated polydimethylsiloxane 1000 into a three-necked flask, heat at 110 °C for 30 min to remove moisture; cool to 60 °C, add 2.58 mL of dicyclohexylmethane diisocyanate and 1 drop of dibutyltin dilaurate catalyst, add dimethyl sulfoxide to adjust the viscosity of the system, stir the reaction under nitrogen protection for 4 h at a stirring speed of 100 r / min to obtain polyurethane prepolymer;

[0059] 0.55 mL of 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane was added to the polyurethane prepolymer, and the reaction was allowed to proceed for 2 h. Then, 0.61 g of 3,9-bis(1,1-dimethyl-2-hydroxyethyl)-2,4,8,10-oxohelicol was added, and the reaction was allowed to proceed for 3 h. Next, 0.76 g of β-cyclodextrin was dissolved in 2 mL of DMSO and added to a flask, where the reaction was allowed to proceed for 2 h. The sample was collected and placed in an 80°C forced-air drying oven to remove the solvent, yielding the medical-grade polyurethane material.

[0060] Weigh 4.0g of medical polyurethane material and add it to 8.0mL of dimethyl sulfoxide solution. Heat and stir at 100℃ and 100r / min. After the material is completely melted, immerse the artificial blood vessel in the polyurethane, then remove the artificial blood vessel and cool it down to allow the polyurethane to adhere evenly to the surface of the artificial blood vessel.

[0061] The artificial blood vessel was then placed in a 60°C forced-air drying oven for 24 hours, and then soaked in deionized water for 7 days, with the water changed daily. This ultimately achieved surface modification of the material using polyurethane to improve its blood compatibility and resistance to calcification.

[0062] Example 3:

[0063] The hydrophilicity of polyurethane materials can also be achieved by replacing some polycarbonate with polyethylene glycol in the soft segments, and by introducing oxalohydrazide into the chain extender to give the polyurethane a higher elastic modulus. At the same time, 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane is still required in the chain extender to maintain good blood compatibility of the entire polyurethane molecule. The preparation and processing method of the polyurethane with multiple silane structures is as follows:

[0064] Weigh 5.0 g of polycarbonate 2000, 3.0 g of polyethylene glycol 2000 and 0.5 g of hydroxyl-terminated polydimethylsiloxane 1000 and add them to a three-necked flask. Heat at 110 °C for 30 min to remove moisture. Cool to 60 °C, add 2.58 mL of dicyclohexylmethane diisocyanate and 1 drop of dibutyltin dilaurate catalyst, add dimethyl sulfoxide to adjust the viscosity of the system, and stir the reaction under nitrogen protection for 4 h at a stirring speed of 100 r / min to obtain polyurethane prepolymer.

[0065] 0.55 mL of 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane was added to the polyurethane prepolymer, and the reaction was carried out for 2 h; then 0.24 g of oxalohydrazide was added, and the reaction was carried out for 2 h; then 0.46 g of 3,9-bis(1,1-dimethyl-2-hydroxyethyl)-2,4,8,10-oxohelicol was added, and the reaction was carried out for 3 h. The sample was collected and placed in an 80℃ forced-air drying oven to remove the solvent, yielding the medical polyurethane material.

[0066] Weigh 4.0g of medical polyurethane material and add it to 2.0mL of dimethyl sulfoxide solution. Heat and stir at 100℃ and 100r / min. Once the material is completely melted, inject the polyurethane into a mold using an injection molding machine to prepare an implant with a specific shape.

[0067] The mold was placed at -20℃ for 24 hours, then opened. The polyurethane implant was then placed in a 60℃ forced-air drying oven for 24 hours, removed, and then soaked in deionized water for 7 days, with the water changed daily. This resulted in a polyurethane implant with good blood compatibility, anti-calcification properties, and fatigue resistance.

[0068] The polyurethane prepared in the above embodiments was subjected to performance testing, and the specific results are as follows:

[0069] Figure 1 The polyurethane of Embodiment 1 of the present invention 1 H NMR spectrum. 1 The peak at 0.05 ppm in the ¹H NMR spectrum originates from the methyl group in 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane, while the peak at 0.09 ppm originates from polydimethylsiloxane. The triplet at 3.3–3.6 ppm represents the four methylene groups linked to the oxygen atom in the 3,9-bis(1,1-dimethyl-2-hydroxyethyl)-2,4,8,10-oxohelix. The three 1:1:1 peaks at 1.14, 1.70, and 4.14 ppm originate from three different methylene groups in polycarbonate, confirming the presence of numerous polycarbonate units in the polyurethane.

[0070] Figure 2 This is a DSC diagram of the polyurethane in Example 1 of the present invention. The polyurethane has a low glass transition temperature (-27.8℃), indicating that its molecular chains are highly flexible. At room temperature, the polyurethane exhibits high elasticity and thus good mechanical properties.

[0071] Figure 3 This is a blood compatibility test of the polyurethane in Example 2 of the present invention. After treating fresh blood with the film for 5 minutes, the adhesion of the material to red blood cells can be clearly observed. It can be seen that no obvious thrombus or large amount of blood deposition appears on the surface of the polyurethane film. This also verifies the good blood compatibility of the material.

[0072] Figure 4 This is Example 3 of the present invention, illustrating calcium deposition in polyurethane under simulated body fluid conditions. After 28 days of treatment with SBF (Simulated Body Fluid), no significant material deposition was observed on the surface of the polyurethane film. EDS observation of the elemental distribution on the material surface revealed no significant concentration of Ca. This indicates that the material exhibits good resistance to calcification.

[0073] The preparation methods of Comparative Examples 1-4 are similar to those of Example 1, the only difference being the molar ratio of the raw materials. The molar ratios of the raw materials and the performance test results of Examples and Comparative Example 1 are listed in Table 1.

[0074] Table 1. Tensile fatigue rate, hemolysis rate, and calcium deposition rate after 10,000 cycles of polyurethane with different proportions.

[0075]

[0076] The long-term blood compatibility, anti-calcification, and fatigue resistance of polyurethane must simultaneously satisfy the integration of silanes and the enhancement of intermolecular interactions. Table 1 shows that Comparative Example 1, lacking the introduction of silanes, exhibited significantly high hemolysis rates and calcium deposition; Comparative Example 2, lacking the introduction of PDMS in the soft segment, showed poor blood compatibility; Comparative Example 3, lacking the introduction of silanes through 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane in the hard segment, also exhibited poor blood compatibility and some calcium deposition. Comparative Example 4, lacking the enhancement of intermolecular interactions through 3,9-bis(1,1-dimethyl-2-hydroxyethyl)-2,4,8,10-oxohelices, resulted in significant fatigue.

[0077] By comparing the tensile fatigue rate, hemolysis rate, and calcium deposition rate of different polyurethane structures, the effects of uniform silane integration and toughening with 3,9-bis(1,1-dimethyl-2-hydroxyethyl)-2,4,8,10-oxohelices on the comprehensive properties of polyurethane films can be investigated. A lack of sufficient silane segments leads to significant blood cell damage and calcium deposition during long-term use. Only the simultaneous introduction of polydimethylsiloxane and 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane can ensure the material's blood compatibility and anti-calcification ability. Simultaneously, the 3,9-bis(1,1-dimethyl-2-hydroxyethyl)-2,4,8,10-oxohelices can significantly improve the fatigue resistance of polyurethane, giving the material long-term mechanical stability. The samples in Examples 1-3 all exhibited good blood compatibility and fatigue resistance, which is beneficial for long-term in vivo use.

[0078] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. A blood-compatible, fatigue-resistant, multi-silicone integrated polyurethane with anti-calcification properties, characterized in that, The polyurethane uses hydroxyl-terminated polycarbonate (PCDL) and polydimethylsiloxane (PDMS) as soft segments, which are polymerized with diisocyanate to prepare a prepolymer. 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane is selected for initial chain extension to introduce a silane structure into the soft segments of the polyurethane. Then, a secondary chain extension is performed using 3,9-bis(1,1-dimethyl-2-hydroxyethyl)-2,4,8,10-oxohelical chain extension. Finally, β-cyclodextrin is added to end-cap the polyurethane elastomer.

2. The preparation method of the anti-calcification, blood-compatible, fatigue-resistant multi-silicon integrated polyurethane according to claim 1, characterized in that, Includes the following steps: (1) PCDL and PDMS are added to a three-necked flask and heated to a molten state at high temperature to obtain a mixture; (2) Cool the mixture obtained in (1) to 50-70℃, add hexamethylene diisocyanate and dibutyltin dilaurate catalyst, stir and react for 2-6 hours under nitrogen protection to obtain polyurethane prepolymer; (3) Add 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane as a chain extender to the polyurethane prepolymer obtained in (2) and react for 1-3 h. (4) Add 3,9-bis(1,1-dimethyl-2-hydroxyethyl)-2,4,8,10-oxohelices to the product obtained in (3) to continue chain extension, and react for 1-2 h; (5) Add β-cyclodextrin as a crosslinking agent to the product obtained in (4) and react for 1-4 h; (6) Collect the product obtained in (5), dry it to remove the solvent, and obtain the final product; (7) The product obtained in (6) is soaked in deionized water to remove small molecules, and then dried again to obtain medical polyurethane elastomer.

3. The preparation method of the anti-calcification, blood-compatible, fatigue-resistant multi-silicon integrated polyurethane according to claim 2, characterized in that, In step (1), the molar ratio of PCDL to PDMS is (1-4):

1.

4. The preparation method of the anti-calcification, blood-compatible, fatigue-resistant multi-silicon integrated polyurethane according to claim 2, characterized in that, In step (2), the molar ratio of hexamethylene diisocyanate to (PCDL+PDMS) is 1:(2-2.5), the molar ratio of dibutyltin dilaurate catalyst to hexamethylene diisocyanate is 0.01:1, and the stirring speed is 60-100 r / min.

5. The preparation method of the anti-calcification, blood-compatible, fatigue-resistant multi-silicon integrated polyurethane according to claim 2, characterized in that, In step (3), the molar ratio of 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane to (PCDL+PDMS) is 0.4:1; And / or, in step (4), the molar ratio of 3,9-bis(1,1-dimethyl-2-hydroxyethyl)-2,4,8,10-oxohelices to (PCDL+PDMS) is 0.4:1; And / or, in step (5), the molar ratio of β-cyclodextrin to (PCDL+PDMS) is 0.2:

1.

6. The preparation method of the anti-calcification, blood-compatible, fatigue-resistant multi-silicon integrated polyurethane according to claim 2, characterized in that, Replace hexamethylene diisocyanate in step (2) with one or more of hexamethylene diisocyanate, lysine diisocyanate, 4,4'-dicyclohexylmethane diisocyanate, and isophorone diisocyanate.

7. The application of the polyurethane of claim 1 or the polyurethane prepared by the method of any one of claims 2 to 6, characterized in that, This includes processing and shaping them into implants, such as artificial heart valves, heart patches, heart occluders, artificial blood vessels, vascular stents, vascular prostheses, balloon catheters, guidewires, and coils.

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