CN119735783A - A calcification-resistant, blood-compatible, fatigue-resistant multi-silicon-integrated polyurethane and its preparation method and application - Google Patents

Abstract

The invention provides calcification-resistant 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 takes hydroxyl-terminated Polycarbonate (PCDL) and Polydimethylsiloxane (PMDS) as soft segments, prepares a prepolymer by polymerization with diisocyanate, selects 1, 3-bis (3-aminopropyl) -1, 3-tetramethyl disiloxane for preliminary chain extension, introduces a silane structure into the soft segments of the polyurethane, then carries out secondary chain extension through 3, 9-bis (1, 1-dimethyl-2-hydroxyethyl) -2,4,8, 10-oxo spiral, and carries out end capping through adding beta-cyclodextrin, thus preparing the polyurethane elastomer. The polyurethane elastomer with excellent biocompatibility, blood compatibility and calcification resistance is prepared by the method. The mechanical properties of the alloy are adjustable, and the alloy is fatigue-resistant, creep-resistant and good in shearing-resistant performance. The polyurethane molecules prepared are easy to compound and modify. Polyurethane has thermoplastic properties and can be adapted to different processing modes for constructing an intracorporal implant with specific requirements.

Description

Calcification-resistant blood-compatible fatigue-resistant multi-silicon integrated polyurethane and preparation method and application thereof

Technical Field

The invention provides calcification-resistant blood-compatible fatigue-resistant multi-silicon integrated polyurethane and a preparation method and application thereof, and belongs to the field of biomedical materials. Through regulating and controlling the silane distribution in the molecular structure, the calcification resistance and the blood compatibility of polyurethane can be realized, and the material has mechanical stability and biocompatibility under long-term use.

Background

With the rapid development of medical technology, there is an increasing demand for high performance biomaterials. Particularly in the field of in vivo implants, there is a higher requirement for the stability of the material over long periods of use. Polyurethane, which is a multifunctional polymer material, is widely used in the medical field due to its excellent mechanical properties, processing convenience and good biocompatibility. However, conventional polyurethane materials may suffer from degradation of mechanical properties, reduced biocompatibility, insufficient calcification resistance, etc. during long-term use, which limits their application in high-end medical implants.

Silane-based materials are generally considered implants with good biocompatibility, but such materials are often difficult to withstand for long-term use due to poor mechanical properties. In addition, the requirements for the blood compatibility and the anti-calcification ability of the materials are more stringent in view of the more severe microenvironment adaptability. This ability has been generally improved by surface modification, but under the long-term use requirements, performance degradation, severe in-vivo tissue degenerative changes, and even secondary surgery risks often occur. How to obtain the stability of long-term in vivo implantation by regulating the structure of polyurethane becomes a key to material design.

The flexible molecular structure of polyurethane provides possibility for structural design under different environments. The improvement of biocompatibility can be achieved by introducing silane segments into the polyurethane. But this in turn leads to a loss of mechanical properties of the material, since there is no significant intermolecular interaction between the silanes. In order to solve the problem, the intermolecular interaction mode can be effectively regulated and controlled by regulating and controlling the components of the chain extender and the cross-linking agent serving as hard segments in the polyurethane, so as to regulate and control the requirements of the polyurethane on mechanical properties under different environments. However, in order to achieve good secondary processing ability of polyurethane, polyurethane needs to be designed as thermoplastic polyurethane with no crosslinking or low crosslinking degree, which further increases the demand for polyurethane structural design.

Against this background, the present invention aims to improve the biocompatibility, calcification resistance and blood compatibility of polyurethane materials by introducing multiple silane structures, while maintaining the mechanical stability thereof over a long period of use. In addition, the thermoplastic polyurethane elastomers developed by the present invention can be flexibly processed to meet specific requirements for material properties for different medical applications to accommodate different medical device and implant designs.

Disclosure of Invention

The first object of the present invention is to provide a calcified blood compatible fatigue resistant multi-silicon integrated polyurethane, which is prepared by polymerizing hydroxy-terminated Polycarbonate (PCDL) and Polydimethylsiloxane (PMDS) together as soft segments with diisocyanate. 1, 3-bis (3-aminopropyl) -1, 3-tetramethyl disiloxane is selected for preliminary chain extension, a silane structure is introduced into a soft segment of polyurethane, then 3, 9-bis (1, 1-dimethyl-2-hydroxyethyl) -2,4,8, 10-oxo-helix secondary chain extension is carried out, and finally beta-cyclodextrin end capping is carried out according to the requirement of mechanical properties to synthesize the polyurethane elastomer.

Wherein the simultaneous introduction of polydimethylsiloxane and 1, 3-bis (3-aminopropyl) -1, 3-tetramethyldisiloxane is used to uniformly integrate silane segments in polyurethane, thereby regulating adaptation to microenvironment. Further, 3, 9-bis (1, 1-dimethyl-2-hydroxyethyl) -2,4,8, 10-oxo-helices are used as chain extenders for the purpose of achieving continuous regeneration of hydrogen bonds between polyurethane molecules for obtaining elastomers with good mechanical stability. Wherein beta-cyclodextrin is used to promote hydrophilicity and effect modification by host-guest interactions. The polyurethane synthesized by the method has thermoplasticity, can be used for material processing by repeated dissolution, and can regulate the viscosity of the polyurethane solvent in the process of the polyurethane solvent by an organic solvent. The polyurethane has stable structure and no mechanical property loss caused by repeated processing.

The polyurethane has the characteristics that the polyurethane elastomer with the evenly integrated silane has good biocompatibility, and can adapt to different microenvironments such as blood, bile, gastric juice, urine, tissue fluid and the like. Polyurethanes have mechanical stability, including fatigue, creep, shear, tear resistance, and can also be used to maintain stable hemodynamics. The polyurethane has the capability of secondary modification through the host-guest effect, and can be suitable for drug loading, structure compounding, interface connection, molecular recognition, substance detection and the like. The polyurethane has thermoplastic properties, can be used for processing into different shapes, and can meet the requirements of implants in different environments, including different medical instruments such as artificial heart valves, heart patches, heart occluders, artificial blood vessels, vascular stents, vascular prostheses, balloon catheters, guide wires, spring rings and the like.

The molecular structure of the polyurethane is required to be designed before preparation, and the method comprises the following steps:

(1) According to the elasticity of the target application scene, the molecular weights of PCDL and PMDS are calculated, and the elastic modulus of polyurethane is regulated and controlled by controlling the molecular weight and the polymerization degree of the prepolymer. Wherein PCDL is used to increase the elastic modulus, and the molecular weight of PDMS is increased to decrease the elasticity. To maintain biocompatibility, the molar ratio of PCDL to PDMS was controlled to be (1-4): 1.

(2) According to the requirements of application scenes on blood compatibility and calcification resistance, the dosage of 1, 3-bis (3-aminopropyl) -1, 3-tetramethyl disiloxane is calculated, and the more the 1, 3-bis (3-aminopropyl) -1, 3-tetramethyl disiloxane is, the better the adhesion resistance of polyurethane is expressed. The amount of 1, 3-bis (3-aminopropyl) -1, 3-tetramethyldisiloxane is always controlled to be not more than one half of the total amount of the chain extender for preventing the material from having a decrease in mechanical properties.

(3) According to the requirement of application scenes on the viscoelasticity of the material, the dosage of 3, 9-bis (1, 1-dimethyl-2-hydroxyethyl) -2,4,8, 10-oxo-helix is regulated. The higher the frequency of deformation under the application environment of the material, the larger the amount of 3, 9-bis (1, 1-dimethyl-2-hydroxyethyl) -2,4,8, 10-oxo-helix, the higher the tan delta of the polyurethane.

(4) According to the requirement of application environment on fatigue resistance, the rest isocyanate is crosslinked by cyclodextrin. The degree of crosslinking is regulated according to the requirements on the toughness of the material, but beta-cyclodextrin is used at most to provide an average of 3 crosslinking points, which would otherwise affect the thermoplasticity of the polyurethane.

The second object of the invention is to provide a preparation method of the calcification-resistant, hemocompatible and fatigue-resistant multi-silicon integrated polyurethane, which comprises the following steps:

(1) Adding PCDL and PMDS into a three-neck flask, heating to a molten state at high temperature to obtain a mixture, wherein the purpose of heating and melting is to remove water, the purpose of removing water is to accurately control in the subsequent reaction process, and side reactions of H ₂ O and isocyanate are eliminated.

(2) And (3) cooling the mixture obtained in the step (1) to 50-70 ℃, adding hexamethylene diisocyanate and a dibutyl tin dilaurate catalyst, and stirring and reacting for 2-6 hours under the protection of nitrogen to obtain the polyurethane prepolymer, wherein in the reaction process, the viscosity of the system is required to be always controlled at the same level, and the viscosity of the system can be controlled by adding dimethyl sulfoxide so as to ensure a stable reaction process.

(3) Adding 1, 3-bis (3-aminopropyl) -1, 3-tetramethyl disiloxane into the polyurethane prepolymer obtained in the step (2) as a chain extender for reacting for 1-3h, wherein the chain extender needs to be dropwise added, and meanwhile, the stirring rotating speed is increased to 200r/min, so that the phenomenon of polymerization explosion caused by too fast and uneven reaction is prevented.

(4) Adding 3, 9-bis (1, 1-dimethyl-2-hydroxyethyl) -2,4,8, 10-oxo spiral into the product obtained in the step (3), continuing to chain extend, reacting for 1-2h, dissolving the 3, 9-bis (1, 1-dimethyl-2-hydroxyethyl) -2,4,8, 10-oxo spiral in DMSO in advance, and then dropwise adding the solution into a system.

(5) And (3) adding beta-cyclodextrin as a cross-linking agent into the product obtained in the step (4) for reacting for 1-4 hours, wherein the beta-cyclodextrin needs to be dried in advance and stored in a dryer. The solid crosslinking agent needs to be dissolved in DMSO in advance, and then the solution is added dropwise to the system.

(6) Collecting the product obtained in step (5), and drying to remove the solvent to obtain a final product;

(7) And (3) placing the product obtained in the step (6) into deionized water to soak and remove small molecules, and then drying again to obtain the medical polyurethane elastomer.

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

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

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

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

Preferably, in step (5), the molar ratio of β -cyclodextrin to (pcdl+pdms) is 0.2:1.

Preferably, in step (6), the drying is performed in an 80 ℃ forced air drying oven.

Preferably, in the step (7), the product obtained in the step (6) is soaked in deionized water for 5-10 days, and the water is changed once a day to ensure that all small molecules in the material are released. And then dried again.

Further, PCDL and PDMS in the step (1) can be replaced by other macromolecule dihydric alcohol. The macromolecular dihydric alcohol has good biocompatibility, good reactivity and good stability, and can be used together with one or more of hydroxyl-terminated polycarbonate, hydroxyl-terminated polycaprolactone, polyethylene glycol anhydride, 1, 4-cyclohexane polyester dihydric alcohol, polytetrahydrofuran, polybasic carboxylic acid isosorbide diol, polyethylene glycol and the like.

Further, hexamethylene diisocyanate in step (2) may also be replaced with other diisocyanates. The diisocyanate used is only good in biocompatibility, free of biotoxicity, good in reactivity and the like, good in stability, and one or more of hexamethylene diisocyanate, lysine diisocyanate, 4' -dicyclohexylmethane diisocyanate and isophorone diisocyanate can be used simultaneously.

Further, the 1, 3-bis (3-aminopropyl) -1, 3-tetramethyldisiloxane in step (3) may also be replaced with other chain extenders. The chain extender used is good in biocompatibility, no biotoxicity, good in reactivity and the like, good in stability, and other small molecular substances including but not limited to 1, 4-butanediol, 1, 6-hexanediol, diethylene glycol, 1, 4-cyclohexanediol, hexamethylenediamine, L-cystine, arginine, dicumyl peroxide and dimethyl silanediol can be additionally introduced.

Further, the beta-cyclodextrin in step (5) may also be replaced with other cross-linking agents. The cross-linking agent selected for synthesizing polyurethane has good biocompatibility, no biotoxicity, good reactivity and the like, has good stability, and can simultaneously use one or more polyhydroxy compounds with a macrocyclic ring and derivatives thereof, including but not limited to hydroxypropyl beta-cyclodextrin and calixarene.

It is a third object of the present invention to provide applications of the polyurethane, including processing thereof, including but not limited to casting, spray forming, reaction injection molding, extrusion molding, compression molding, variable fiber injection molding, and the like.

Further, the casting molding comprises the following steps:

(1) Weighing the medical polyurethane elastomer prepared by the method, adding the medical polyurethane elastomer into a dimethyl sulfoxide solution, heating and stirring the medical polyurethane elastomer, and preventing DMSO loss when the elastomer is completely melted to obtain a polyurethane solution with the weight percent of 20-80 ℃, wherein the heating temperature is 80-120 ℃, and the stirring speed is 50r/min;

(2) The polyurethane solution in the step (1) is added into an injection molding machine to be injected into a mold, or is directly poured into the mold to be leveled into a film.

(3) And (3) putting polyurethane and a mold into a cooling, shaping and demolding at the temperature of-20 ℃, and then putting the polyurethane and the mold into a blast drying box at the temperature of 60 ℃ for removing a large amount of organic solvent in the polyurethane until the shape of the polyurethane is completely fixed.

(4) And (3) placing the polyurethane material obtained in the step (3) in ionized water for soaking for 7 days, and changing water once a day to ensure that all small molecules in the material are released, so as to obtain a final product.

The polyurethane elastomer with excellent biocompatibility, blood compatibility and calcification resistance is prepared by the method. The mechanical properties of the alloy are adjustable, and the alloy is fatigue-resistant, creep-resistant and good in shearing-resistant performance. The polyurethane molecules prepared are easy to compound and modify. Polyurethane has thermoplastic properties and can be adapted to different processing modes for constructing an intracorporal implant with specific requirements.

The fatigue-resistant polyurethane material with long-term blood compatibility and calcification resistance designed by the invention has the advantages of multi-morphology, multi-occasion adaptability, simple operation, good biocompatibility and proper mechanical properties. Long-term implant designs that can be used in a variety of complex in vivo environments include prosthetic heart valves, cardiac patches, heart occluders, vascular prostheses, vascular stents, vascular prostheses, balloon catheters, guidewires, coils, and the like.

Compared with the prior art, the invention has the following advantages and beneficial effects:

1. The invention provides polyurethane with multiple introduced silane structures. The polyurethane introduces polydimethylsiloxane in the soft segment, so that good biocompatibility can be realized. The polyurethane regulates the adaptation capability of the polyurethane to different tissue microenvironments through 1, 3-bis (3-aminopropyl) -1, 3-tetramethyl disiloxane. The polyurethane controls the elastic modulus by regulating and controlling the proportion and the molecular weight of soft segments, and realizes good fatigue resistance by regulating and controlling the intermolecular interaction through 3, 9-di (1, 1-dimethyl-2-hydroxyethyl) -2,4,8, 10-oxo spiral and local high-density hydrogen bonds.

2. The polyurethane synthesized by the invention has host-guest identification and inclusion capacity, can be used for being combined with other materials, has thermoplasticity, meets various different processing modes, and can meet the blood compatibility and calcification resistance required by in-vivo implantation. Can realize the regulation and control of viscoelasticity, meet the deformation requirements under different frequencies, has good shearing resistance and can realize the operation mode of suture implantation.

Drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for the description of the embodiments will be briefly described below, and it is apparent that the drawings in the following description are only some embodiments of the present invention, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.

FIG. 1 is a ¹ H NMR chart of the polyurethane of example 1 of the present invention;

FIG. 2 is a DSC of the polyurethane of example 1 of the present invention;

FIG. 3 is a blood compatibility test of polyurethane of example 2 of the present invention;

FIG. 4 is a graph showing calcium deposition of the polyurethane of example 3 of the present invention under simulated body fluids.

Detailed Description

In order to make the technical problems, technical solutions and advantages to be solved more apparent, the following detailed description will be given with reference to the accompanying drawings and specific embodiments.

Example 1

To achieve the need for blood compatibility and anti-calcification capacity, the molar ratio of 1, 3-bis (3-aminopropyl) -1, 3-tetramethyldisiloxane to 3, 9-bis (1, 1-dimethyl-2-hydroxyethyl) -2,4,8, 10-oxo-helices is 1:1. But not crosslinked by beta-cyclodextrin, is mainly used for preparing a hydrophobic film, and simultaneously has lower toughness. The preparation and processing method of the polyurethane with multiple introduced silane structures comprises the following steps:

weighing 8.0g of hydroxyl-terminated polycarbonate 2000 and 0.5g of hydroxyl-terminated polydimethylsiloxane 500, adding into a three-neck flask, heating for 30min at 110 ℃, removing water, cooling to 60 ℃, adding 1.61mL of hexamethylene diisocyanate and 1 drop of dibutyltin dilaurate catalyst, adding dimethyl sulfoxide to regulate the viscosity of the system, and stirring under the protection of nitrogen for reaction for 3h at the stirring speed of 100r/min to obtain polyurethane prepolymer;

adding 0.69mL of 1, 3-bis (3-aminopropyl) -1, 3-tetramethyl disiloxane into the polyurethane prepolymer for reaction for 1.5h, then adding 0.76g of 3, 9-bis (1, 1-dimethyl-2-hydroxyethyl) -2,4,8, 10-oxo spiral for reaction for 2h, collecting a sample, and placing the sample in an 80 ℃ air drying oven for removing the solvent to obtain a medical polyurethane material;

Weighing 2.0g of medical polyurethane material, adding the polyurethane material into 6.0mL of dimethyl sulfoxide solution, heating and stirring at 100 ℃ and stirring speed of 100r/min, and pouring the polyurethane solution into a polytetrafluoroethylene mould to be leveled to form a film when the material is completely melted.

And then placing the film in a 60 ℃ air-blast drying box for 24 hours, taking out the film, soaking the film in deionized water, and storing for 7 days, and changing water once a day to obtain the polyurethane film with good blood compatibility and calcification resistance.

Example 2

In order to achieve good toughness of the material, the crosslinking degree of polyurethane is improved through beta-cyclodextrin, and in order to maintain the hydrophobicity of the polyurethane material, polydimethylsiloxane 1000 with higher molecular weight is used in a soft segment area for maintaining the blood compatibility and calcification resistance of the material. The preparation and processing method of the polyurethane with multiple introduced silane structures comprises the following steps:

weighing 5.0g of polytetrahydrofuran 2000 and 2.5g of hydroxyl-terminated polydimethylsiloxane 1000, adding into a three-neck flask, heating for 30min at 110 ℃, removing water, cooling to 60 ℃, adding 2.58mL of dicyclohexylmethane diisocyanate and 1 drop of dibutyltin dilaurate catalyst, adding dimethyl sulfoxide to regulate the viscosity of the system, and stirring under the protection of nitrogen for reacting for 4h at the stirring speed of 100r/min to obtain polyurethane prepolymer;

To the polyurethane prepolymer, 0.55mL of 1, 3-bis (3-aminopropyl) -1, 3-tetramethyldisiloxane was added to react for 2 hours, then 0.61g of 3, 9-bis (1, 1-dimethyl-2-hydroxyethyl) -2,4,8, 10-oxo-helix was added to react for 3 hours, then 0.76g of beta-cyclodextrin was weighed to dissolve in 2mL of DMSO, and added to react for 2 hours. Collecting a sample, and placing the sample in an 80 ℃ air blast drying box to remove the solvent to obtain a medical polyurethane material;

Weighing 4.0g of medical polyurethane material, adding the polyurethane material into 8.0mL of dimethyl sulfoxide solution, heating and stirring at 100 ℃ at the stirring speed of 100r/min, completely melting the material, soaking the artificial blood vessel in the polyurethane, taking out the artificial blood vessel, and cooling to enable the polyurethane to be uniformly adhered on the surface of the artificial blood vessel.

Then the artificial blood vessel is placed in a 60 ℃ blast drying box for 24 hours, taken out, soaked in deionized water and stored for 7 days, and water is changed once a day. Finally, the surface modification of the material by polyurethane is realized, and the polyurethane is used for improving the blood compatibility and calcification resistance of the material.

Example 3:

The hydrophilicity of the polyurethane material can also be realized by replacing part of polycarbonate with polyethylene glycol in the soft segment, and the oxalyl dihydrazide is introduced into the chain extender, so that the polyurethane has higher elastic modulus. At the same time, 1, 3-bis (3-aminopropyl) -1, 3-tetramethyldisiloxane is still needed in the chain extender to maintain good blood compatibility throughout the polyurethane molecule. The preparation and processing method of the polyurethane with multiple introduced silane structures comprises the following steps:

Weighing 5.0g of polycarbonate 2000,3.0g of polyethylene glycol 2000 and 0.5g of hydroxyl-terminated polydimethylsiloxane 1000, adding into a three-neck flask, heating at 110 ℃ for 30min, removing water, cooling to 60 ℃, adding 2.58mL of dicyclohexylmethane diisocyanate and 1 drop of dibutyltin dilaurate catalyst, adding dimethyl sulfoxide to regulate the viscosity of the system, and stirring under the protection of nitrogen for reacting for 4h at the stirring speed of 100r/min to obtain polyurethane prepolymer;

To the polyurethane prepolymer, 0.55mL of 1, 3-bis (3-aminopropyl) -1, 3-tetramethyldisiloxane was added to react for 2 hours, followed by the addition of 0.24g of oxalyl dihydrazide to react for 2 hours, followed by the addition of 0.46g of 3, 9-bis (1, 1-dimethyl-2-hydroxyethyl) -2,4,8, 10-oxo-helix to react for 3 hours. Collecting a sample, and placing the sample in an 80 ℃ air blast drying box to remove the solvent to obtain a medical polyurethane material;

Weighing 4.0g of medical polyurethane material, adding the polyurethane material into 2.0mL of dimethyl sulfoxide solution, heating and stirring at 100 ℃ at the stirring speed of 100r/min, and injecting polyurethane into a mold through an injection molding machine to prepare the implant with a specific shape when the material is completely melted.

The mold was placed at-20 ℃ for 24h and opened. The polyurethane implant was then placed in a 60 ℃ forced air drying oven for 24 hours, removed, immersed in deionized water, and stored for 7 days, changing water once a day. Finally, the polyurethane implant with good blood compatibility, calcification resistance and fatigue resistance is obtained.

The polyurethane prepared in the above example was subjected to performance test, and the specific results are as follows:

FIG. 1 is a ¹ H NMR chart of the polyurethane of example 1 of the present invention. ¹ The peak at 0.05ppm in H NMR was derived from methyl in 1, 3-bis (3-aminopropyl) -1, 3-tetramethyldisiloxane, and the peak at 0.09ppm was derived from polydimethylsiloxane. The triplet at 3.3-3.6ppm is then the four methylene groups in the 3, 9-bis (1, 1-dimethyl-2-hydroxyethyl) -2,4,8, 10-oxo helix attached to the O element. The three 1:1:1 peaks at 1.14, 1.70 and 4.14ppm were derived from three different states of methylene in the polycarbonate, which verifies the presence of a large number of polycarbonate units in the polyurethane.

FIG. 2 is a DSC of the polyurethane of example 1 of the present invention. The polyurethane has a lower glass transition temperature (-27.8 ℃) and has larger flexibility of molecular chains, and the polyurethane has high elasticity at normal temperature and can show good mechanical properties.

FIG. 3 is a blood compatibility test of polyurethane of example 2 of the present invention. After the fresh blood is treated by the film for 5min, the adhesion of the material to red blood cells can be visually observed, and no obvious thrombus or massive blood deposition can be seen on the surface of the polyurethane film. This also verifies the good blood compatibility of the material.

FIG. 4 is a graph showing calcium deposition of the polyurethane of example 3 of the present invention under simulated body fluids. After 28 days of body fluid treatment by SBF simulation, no significant deposition of material on the polyurethane film surface occurred. By observing the elemental distribution of the material surface by EDS, it can be seen that no significant concentration of Ca elements occurs. This indicates that the material has good anti-calcification ability.

The preparation of comparative examples 1 to 4 is similar to example 1, except that the molar ratio of the starting materials is different. The raw material molar ratios and performance test results of the examples and comparative example 1 are shown in table 1.

TABLE 1 cycle 10000 times tensile fatigue, hemolysis and calcium deposition of polyurethanes of different proportions

The long-term blood compatibility, calcification resistance and fatigue resistance of polyurethane are required to meet the requirement of integration of silane and strengthening of intermolecular action. From table 1, it is clear that comparative example 1 shows significantly high hemolysis and calcium deposition due to no silane introduced, comparative example 2 shows poor blood compatibility due to no PDMS introduced in the soft segment, and comparative example 3 shows poor blood compatibility due to no silane introduced through 1, 3-bis (3-aminopropyl) -1, 3-tetramethyldisiloxane in the hard segment, while some calcium deposition occurs. Comparative example 4 the material was significantly fatigued because the intermolecular interactions were not enhanced by 3, 9-bis (1, 1-dimethyl-2-hydroxyethyl) -2,4,8, 10-oxo helices.

By comparing the tensile fatigue rate, the hemolysis rate and the calcium deposition rate of different polyurethane structures, the influence of silane uniform integration and 3, 9-bis (1, 1-dimethyl-2-hydroxyethyl) -2,4,8, 10-oxo spiral toughening on the comprehensive performance of the polyurethane film can be studied. Wherein the lack of sufficient silane linkage leads to significant blood cell destruction and calcium deposition during long-term use, only the simultaneous introduction of polydimethylsiloxane and 1, 3-bis (3-aminopropyl) -1, 3-tetramethyldisiloxane ensures the blood compatibility and anticalcification capability of the material. Meanwhile, 3, 9-di (1, 1-dimethyl-2-hydroxyethyl) -2,4,8, 10-oxo-helix can obviously improve the fatigue resistance of polyurethane, so that the material has long-term use mechanical stability. The samples of examples 1-3 all exhibited good blood compatibility and fatigue resistance. Is beneficial to long-term use in vivo.

The foregoing is merely illustrative of the present invention, and the present invention is not limited thereto, and any person skilled in the art will readily recognize that variations or substitutions are within the scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.

Claims (10)

1. The calcified blood compatible fatigue resistant multi-silicon integrated polyurethane is characterized in that hydroxyl-terminated Polycarbonate (PCDL) and Polydimethylsiloxane (PMDS) are taken as soft segments of the polyurethane, prepolymer is prepared by polymerization with diisocyanate, 1, 3-bis (3-aminopropyl) -1, 3-tetramethyl disiloxane is selected for preliminary chain extension, a silane structure is introduced into the soft segments of the polyurethane, and then 3, 9-bis (1, 1-dimethyl-2-hydroxyethyl) -2,4,8, 10-oxo spiral secondary chain extension is carried out, and beta-cyclodextrin end capping is added to prepare the polyurethane elastomer.

2. The method for preparing the calcified blood compatible fatigue resistant multi-silicon integrated polyurethane according to claim 1, comprising the following steps:

(1) Adding PCDL and PMDS into a three-neck flask, and heating to a molten state at a high temperature to obtain a mixture;

(2) Cooling the mixture obtained in the step (1) to 50-70 ℃, adding hexamethylene diisocyanate and a dibutyltin dilaurate catalyst, and stirring and reacting for 2-6 hours under the protection of nitrogen to obtain polyurethane prepolymer;

(3) Adding 1, 3-bis (3-aminopropyl) -1, 3-tetramethyl disiloxane as a chain extender into the polyurethane prepolymer obtained in the step (2), and reacting for 1-3h;

(4) Adding 3, 9-bis (1, 1-dimethyl-2-hydroxyethyl) -2,4,8, 10-oxo spiral into the product obtained in the step (3) to continue chain extension, and reacting for 1-2h;

(5) Adding beta-cyclodextrin as a cross-linking agent into the product obtained in the step (4), and reacting for 1-4h;

(6) Collecting the product obtained in step (5), and drying to remove the solvent to obtain a final product;

(7) And (3) placing the product obtained in the step (6) into deionized water to soak and remove small molecules, and then drying again to obtain the medical polyurethane elastomer.

3. The method for preparing the calcified blood compatible fatigue resistant multi-silicon integrated polyurethane according to claim 2, wherein in the step (1), the molar ratio of PCDL to PDMS is (1-4): 1.

4. The method for preparing the calcified blood compatible fatigue resistant multi-silicon integrated polyurethane according to claim 2, wherein in the step (2), the molar ratio of the hexamethylene diisocyanate to (PCDL+PDMS) is 1 (2-2.5), the molar ratio of the dibutyl tin dilaurate catalyst to the hexamethylene diisocyanate is 0.01:1, and the stirring speed is 60-100 r/min.

5. The method for preparing the calcified hemocompatible fatigue-resistant multi-silicon integrated polyurethane according to claim 2, wherein in the step (3), the molar ratio of 1, 3-bis (3-aminopropyl) -1, 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-oxo-helic to (pcdl+pdms) is 0.4:1;

and/or, in step (5), the molar ratio of beta-cyclodextrin to (PCDL+PDMS) is 0.2:1.

6. The method for preparing the calcified blood compatible fatigue resistant multi-silicon integrated polyurethane according to claim 2, wherein PCDL and PDMS in the step (1) are replaced by one or more of hydroxyl-terminated polycarbonate, hydroxyl-terminated polycaprolactone, polyethylene terephthalate glycol, 1, 4-cyclohexane polyester diol, polytetrahydrofuran, polysorbates, and polyethylene glycol.

7. The method for preparing the calcified blood compatible fatigue resistant multi-silicon integrated polyurethane according to claim 2, wherein the hexamethylene diisocyanate in the step (2) is replaced by one or more of hexamethylene diisocyanate, lysine diisocyanate, 4' -dicyclohexylmethane diisocyanate and isophorone diisocyanate.

8. The method for preparing the calcified hemocompatible fatigue-resistant multiple silicon integrated polyurethane according to claim 2, wherein 1, 3-bis (3-aminopropyl) -1, 3-tetramethyldisiloxane in the step (3) is replaced by one or more of 1, 4-butanediol, 1, 6-hexanediol, diethylene glycol, 1, 4-cyclohexanediol, hexamethylenediamine, L-cystine, arginine, dicumyl peroxide and dimethylsilanediol.

9. The method for preparing the calcified blood compatible fatigue resistant multi-silicon integrated polyurethane according to claim 2, wherein the beta-cyclodextrin in the step (5) is replaced by one or more of hydroxypropyl beta-cyclodextrin and calixarene.

10. Use of the polyurethane of claim 1 or the polyurethane prepared by the method of any one of claims 2 to 9, comprising shaping it as an in vivo implant for artificial heart valves, heart patches, heart occluders, vascular prostheses, vascular stents, vascular prostheses, balloon catheters, guidewires, spring coils.