Polyurethane materials and methods of making and use

Abstract

The application provides a polyurethane material, a preparation method and application. The obtained polyurethane material has good mechanical properties and biological stability, and meets the long-term implantation requirement.

Description

Technical Field

[0001] This invention relates to the field of biomaterials technology, and in particular to a polyurethane material, its preparation method, and its application. Background Technology

[0002] Polyurethane is a biocompatible material with excellent fatigue resistance. Research on its application in heart valve leaflets began in the 1960s. Polyurethane heart valves show good results in in vitro fatigue testing; reportedly, bileaflet mitral valves with PCU (polyurethane carbonate) have withstood 1 billion fatigue cycles, equivalent to a 26-year lifespan, far exceeding the 200 million cycles required for bioprosthetic valves. However, conventional animal experiments on polyurethane heart valves show poor biostability. Polyester-based polyurethanes are prone to hydrolysis, polyether-based polyurethanes are prone to oxidation, and polycarbonate still carries a risk of hydrolysis with long-term use, and its anti-calcification properties remain insufficient.

[0003] While siloxane-modified polyurethane has demonstrated good biostability through long-term clinical trials, its mechanical properties are insufficient when applied to heart valves, making it prone to structural failure. The development of interventional polymeric heart valves is currently progressing slowly, primarily because the addition of significant amounts of organosilicon to polyurethane materials noticeably affects their mechanical properties. Therefore, there is still a need to develop polyurethane materials with high tensile and tear strength, as well as long-term biostability. Summary of the Invention

[0004] The technical problem to be solved by this invention is the deficiency in existing polyurethane research that mechanical properties and biological stability cannot be simultaneously achieved, thereby providing a polyurethane material with good mechanical properties and biological stability to meet the needs of long-term implantation.

[0005] A method for preparing a polyurethane material includes the following steps:

[0006] S1: Weigh out small molecules with multiple hydrogen bonds, add organic solvent and stir to make the small molecules with multiple hydrogen bonds dispersed and suspended in the organic solvent, add aliphatic diisocyanate, and stir and react at 40-80℃ for 0.5-4h under nitrogen protection to obtain aliphatic diisocyanate-terminated multiple hydrogen bond-enhanced segments.

[0007] S2: Weigh hydroxyl-terminated polydimethylsiloxane, dehydrate it under vacuum at 100-130℃ for 1-3 hours, lower the temperature to 60-80℃, add phenyl diisocyanate, and react at 60-80℃ for 2-4 hours under nitrogen protection to obtain prepolymerized hydroxyl-terminated polydimethylsiloxane.

[0008] S3: Dehydrate the polyol and the prepolymerized hydroxyl-terminated polydimethylsiloxane respectively;

[0009] S4: Weigh the phenyl diisocyanate and the aliphatic diisocyanate end-capped multiple hydrogen bond reinforced segments, stir and heat under nitrogen protection, add the dehydrated polypolyol and the dehydrated prepolymerized hydroxyl-terminated polydimethylsiloxane, and react to obtain the prepolymer.

[0010] S5: Add a chain extender to the prepolymer and react to obtain the polyurethane material, wherein the polyurethane material is a polyurethane material modified with multiple hydrogen bonds and enhanced with organosilicon.

[0011] The polyurethane material prepared by the above method is a polyurethane material modified with multiple hydrogen bonds and reinforced with organosilicon. The beneficial effects of this preparation method are as follows:

[0012] 1. The soft segment portion of the main molecular chain of the polyurethane material includes prepolymerized hydroxyl-terminated polydimethylsiloxane. The silicon segments of the prepolymerized hydroxyl-terminated polydimethylsiloxane can migrate and accumulate to the surface, improving the material's resistance to biodegradation, calcification, and thrombosis, and giving the material good biocompatibility. The soft segment portion also contains polyol segments, giving the material good flexibility and strength.

[0013] 2. The prepolymerized hydroxyl-terminated polydimethylsiloxane in the soft segment is prepared by prepolymerization of dehydrated hydroxyl-terminated polydimethylsiloxane and phenyl diisocyanate. This improves the regularity of the silicon-containing chain segments in the soft segment, which can improve the degree of phase separation of the material and enhance the mechanical and biological properties of the material.

[0014] 3. The main molecular chain of the polyurethane is made of phenyl diisocyanate. Polyurethane prepared by phenyl diisocyanate has good in vivo biological stability and better hydrolysis resistance than polyurethane materials prepared by aliphatic diisocyanate. The aliphatic diisocyanate end-capped multiple hydrogen bond reinforced chain segment used in polyurethane materials contains relatively little aliphatic diisocyanate, which does not affect biological stability.

[0015] 4. Small molecules with multiple hydrogen bonds are readily soluble in water but difficult to dissolve in most organic solvents. Therefore, introducing these small molecules into polyurethane segments is challenging. Directly adding them during preparation can easily lead to incomplete reactions and the formation of insoluble precipitates in the reactants. Before introducing these small molecules into the polyurethane segments, end-capping modification with aliphatic diisocyanates yields well-soluble aliphatic diisocyanate-terminated multi-hydrogen bond-reinforced segments. These segments form clear solutions in organic solvents, allowing for complete reaction with the reactants and the preparation of high-performance polyurethane materials. The aliphatic diisocyanate is chosen for end-capping because while benzene ring-containing diisocyanates offer good bulk stability, they can impede the free rotation of hydrogen-bonded segments and hinder the formation of hydrogen bonds between hydrogen-bonded groups, thus failing to achieve the desired hydrogen bond reinforcement. Therefore, by end-capping the small molecules with multiple hydrogen bonds using aliphatic diisocyanate, the degree of reaction of the small molecules with multiple hydrogen bonds is improved, and the formation of multiple hydrogen bonds in the polyurethane segments is ensured. This results in the prepared polyurethane material having good comprehensive mechanical strength, which compensates for the decrease in mechanical properties caused by the use of polydimethylsiloxane segments, while also ensuring that the material has good flexibility. Attached Figure Description

[0016] Various other advantages and benefits will become apparent to those skilled in the art upon reading the following detailed description of preferred embodiments. The accompanying drawings are for illustrative purposes only and are not intended to limit the invention. Furthermore, the same reference numerals denote the same parts throughout the drawings. Wherein:

[0017] Figure 1 The infrared spectra of the polyurethane materials prepared in Examples 1 and 2 and the polyurethane materials in Comparative Examples 1 and 2 are shown.

[0018] Figure 2 The pathological analysis of the bovine pericardium mentioned in Test Example 3 after 8 weeks (a / b / c are Alizarin Red staining, d / e / f are H&E staining).

[0019] Figure 3 The pathological analysis of the polyurethane material obtained in Example 1 mentioned in Test Example 3 after 8 weeks (a / b / c are Alizarin Red staining, d / e / f are H&E staining). Detailed Implementation

[0020] Exemplary embodiments of the invention will now be described in more detail with reference to the accompanying drawings. While exemplary embodiments of the invention are shown in the drawings, it should be understood that the invention can be implemented in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided to enable a more thorough understanding of the invention and to fully convey the scope of the invention to those skilled in the art.

[0021] It should be understood that the terminology used herein is for the purpose of describing particular exemplary embodiments only and is not intended to be limiting. Unless the context clearly indicates otherwise, the singular forms “a,” “an,” and “described” as used herein may also include the plural forms. The terms “comprising,” “including,” “containing,” and “having” are inclusive and therefore indicate the presence of the stated features, steps, operations, elements, and / or components, but do not exclude the presence or addition of one or more other features, steps, operations, elements, components, and / or combinations thereof. The method steps, processes, and operations described herein are not construed as requiring them to be performed in a particular order described or illustrated unless the order of performance is explicitly indicated. It should also be understood that additional or alternative steps may be used.

[0022] This invention provides a method for preparing a polyurethane material, comprising the following steps:

[0023] S1: Weigh out small molecules with multiple hydrogen bonds, add organic solvent and stir to make the small molecules with multiple hydrogen bonds dispersed and suspended in the organic solvent, add aliphatic diisocyanate, and stir and react at 40-80℃ for 0.5-4h under nitrogen protection to obtain aliphatic diisocyanate-terminated multiple hydrogen bond-enhanced segments.

[0024] S2: Weigh hydroxyl-terminated polydimethylsiloxane, dehydrate it under vacuum at 100-130℃ for 1-3 hours, lower the temperature to 60-80℃, add phenyl diisocyanate, and react at 60-80℃ for 2-4 hours under nitrogen protection to obtain prepolymerized hydroxyl-terminated polydimethylsiloxane.

[0025] S3: Dehydrate the polyol and the prepolymerized hydroxyl-terminated polydimethylsiloxane respectively;

[0026] S4: Weigh the phenyl diisocyanate and the aliphatic diisocyanate end-capped multiple hydrogen bond reinforced segments, stir and heat under nitrogen protection, add the dehydrated polypolyol and the dehydrated prepolymerized hydroxyl-terminated polydimethylsiloxane, and react to obtain the prepolymer.

[0027] S5: Add a chain extender to the prepolymer and react to obtain the polyurethane material, wherein the polyurethane material is a polyurethane material modified with multiple hydrogen bonds and enhanced with organosilicon.

[0028] In step S1, the molecular formula of the aliphatic diisocyanate-terminated multi-hydrogen bond-reinforced segment is either formula (1) or formula (2) as follows:

[0029]

[0030] R1 is an aliphatic segment, and R2 is a segment containing multiple hydrogen bonds.

[0031]

[0032] Specifically, the chemical equations for the preparation of aliphatic diisocyanate-terminated multi-hydrogen bond-reinforced segments are as follows (1) and (2):

[0033] In this embodiment, the aliphatic diisocyanate and the multiple hydrogen-bonded small molecule are mixed in a molar ratio of 2:1. The multiple hydrogen-bonded small molecule includes oxaloacetic dihydrazide, succinic dihydrazide, adipic dihydrazide, imidazolidinyl urea, or ureidinidone. It is understood that in this embodiment, the molecular formula of imidazolidinyl urea contains hydroxyl groups (-OH) at both ends, which meets the reaction conditions of molecular formula (1); the molecular formulas of oxaloacetic dihydrazide, succinic dihydrazide, and adipic dihydrazide contain amino groups (-NH2) at both ends, which meets the reaction conditions of molecular formula (2). In other embodiments, ureidinidone may include 5-(2-hydroxyethyl)-6-methyl-2-aminouracil, wherein the molecular formula of 5-(2-hydroxyethyl)-6-methyl-2-aminouracil contains hydroxyl groups (-OH) and amino groups (-NH2) at both ends, and the above preparation method can also be performed.

[0034] Aliphatic diisocyanates include hexamethylene diisocyanate (HDI), isophorone diisocyanate (IPDI), dicyclohexylmethane diisocyanate (HMDI), or lysine diisocyanate (LDI). Organic solvents can be N,N-dimethylformamide (DMF), dimethylacetamide (DMAC), acetone, toluene, etc.

[0035] In this embodiment, the multi-hydrogen-bonded small molecules are readily soluble in water but difficult to dissolve in most organic solvents. Therefore, introducing these small molecules into the polyurethane chain is challenging. Directly adding them during the preparation process can easily lead to incomplete reactions and the formation of insoluble precipitates in the reactants. Before introducing the multi-hydrogen-bonded small molecules into the polyurethane chain, end-capping modification with aliphatic diisocyanates yields aliphatic diisocyanate-terminated multi-hydrogen-bonded reinforced segments with good solubility. These segments form clear solutions in organic solvents, allowing for complete reaction with the reactants and the preparation of high-performance polyurethane materials. The aliphatic diisocyanate is chosen for end-capping because while benzene ring-containing diisocyanates offer good in-situ stability, they can impair the free rotation of hydrogen-bonded segments and the formation of hydrogen bonds between hydrogen-bonded groups, making it difficult to achieve the desired hydrogen bond enhancement. Therefore, by end-capping the small molecules with multiple hydrogen bonds using aliphatic diisocyanate, the degree of reaction of the small molecules with multiple hydrogen bonds is improved, and the formation of multiple hydrogen bonds in the polyurethane segments is ensured. This results in the prepared polyurethane material having good comprehensive mechanical strength, which compensates for the decrease in mechanical properties caused by the use of polydimethylsiloxane segments, while also ensuring that the material has good flexibility.

[0036] In step S2, the chemical equation for the preparation of prepolymerized hydroxyl-terminated polydimethylsiloxane is as follows:

[0037]

[0038] The hydroxyl-terminated polydimethylsiloxane and phenyl diisocyanate are present in a molar ratio of 2:1. The hydroxyl-terminated polydimethylsiloxane includes one or more of bis(hydroxypropyl)polydimethylsiloxane, α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane, and bis(hydroxybutyl)polydimethylsiloxane. In this embodiment, the number-average molecular weight of the hydroxyl-terminated polydimethylsiloxane is 500-5000, preferably 1000-2000. If the number-average molecular weight of the hydroxyl-terminated polydimethylsiloxane is too low, the prepared material is hard and has poor flexibility; if the number-average molecular weight of the hydroxyl-terminated polydimethylsiloxane is too high, the prepared material is soft but has poor mechanical strength.

[0039] This prepolymerized hydroxyl-terminated polydimethylsiloxane is prepared by prepolymerization of dehydrated hydroxyl-terminated polydimethylsiloxane and phenyl diisocyanate. It improves the regularity of the silicon-containing chain segments in the soft segment, thereby enhancing the degree of microphase separation and improving the material's mechanical properties and antithrombotic and other biological properties. The dehydration of the hydroxyl-terminated polydimethylsiloxane is to remove excess adsorbed water.

[0040] In step S3, in one embodiment, the polyol and the prepolymerized hydroxyl-terminated polydimethylsiloxane are vacuum dehydrated at 100-130°C for 1-3 hours. The polyol includes polycarbonate polyols and polyether polyols. The polycarbonate polyols include poly(1,6-hexyl carbonate) diol, poly(1,6-hexyl-1,2-ethyl carbonate) diol, poly(1,8-octanediol carbonate) diol, and poly(1,10-decanediol carbonate) diol; the polyether polyols include one or more of polytetrahydrofurandiol, poly(1,6-hexanediol), poly(1,8-octanediol), and poly(1,10-decanediol). The number-average molecular weight of the polyol is 1000-4000. If the number-average molecular weight of the polyol is too low, the prepared material is hard and has poor flexibility; if the number-average molecular weight of the polyol is too high, the prepared material is soft but has poor mechanical strength.

[0041] The soft segment of the main molecular chain of this polyurethane material includes polydimethylsiloxane. The silicon segments of polydimethylsiloxane can migrate and accumulate to the surface, improving the material's resistance to biodegradation, calcification, and thrombosis, and giving the material good biocompatibility. The soft segment also contains polypolyol segments, which give the material good flexibility and strength.

[0042] In step S4, in one embodiment, phenyl diisocyanate and aliphatic diisocyanate end-capped multiple hydrogen bond-reinforced segments are weighed, stirred and heated to 60-80°C under nitrogen protection, and then dehydrated polypolyol and dehydrated prepolymerized hydroxyl-terminated polydimethylsiloxane are added. The reaction is carried out for 1-3 hours to obtain the prepolymer. The phenyl diisocyanate includes one or more of toluene diisocyanate (TDI), diphenylmethane diisocyanate (MDI), and naphthalene diisocyanate (NDI).

[0043] In this preparation method, the molar ratio of phenyl diisocyanate to aliphatic diisocyanate-terminated multiple hydrogen bond-reinforced segments is 1:0.05-1.3. The phenyl diisocyanate used in this preparation method includes the phenyl diisocyanate used in steps S2 and S4.

[0044] The main molecular chain of this polyurethane is made of phenyl diisocyanate. Polyurethane prepared from phenyl diisocyanate has good in vivo biological stability and better hydrolysis resistance than polyurethane materials prepared from aliphatic diisocyanate. In contrast, the aliphatic diisocyanate-terminated multi-hydrogen bond-reinforced segments used in polyurethane materials contain relatively little aliphatic diisocyanate, which does not affect biological stability.

[0045] In step S5, in one embodiment, a chain extender is added to the prepolymer. When the chain extender is a small molecule diol, the reaction conditions are 80-130°C for 4-48 hours to obtain the polyurethane material; when the chain extender is a small molecule diamine, the reaction conditions are -10-40°C for 1-8 hours to obtain the polyurethane material. The chain extender may include a small molecule diol or a small molecule diamine. The small molecule diol may include ethylene glycol, 1,4-butanediol, and 1,6-hexanediol, and the small molecule diamine may include ethylenediamine, butanediamine, hexanediamine, and phenylenediamine.

[0046] In one embodiment, the chemical reaction process in steps S4 and S5 is as follows:

[0047]

[0048] in:

[0049]

[0050] In the prepolymer α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane, R4 is an aliphatic carbon segment or an ether-containing carbon segment.

[0051] In this embodiment, the multi-hydrogen bond-reinforced silicone-modified polyurethane material obtained through the above steps is a thermoplastic elastomer. The main molecular chain of this polyurethane material includes hard segments and soft segments. The hard segments are composed of at least phenyl diisocyanate, aliphatic diisocyanate-terminated multi-hydrogen bond-reinforced segments, and a chain extender. The soft segments are composed of at least a polyol and a prepolymerized hydroxyl-terminated polydimethylsiloxane. Introducing hydroxyl-terminated polydimethylsiloxane into the soft segments enhances the hydrolysis resistance and biocompatibility of the polyurethane material, while introducing aliphatic diisocyanate-terminated multi-hydrogen bond-reinforced segments into the hard segments enhances the mechanical properties of the polyurethane material.

[0052] In this embodiment, the mass of phenyl diisocyanate, aliphatic diisocyanate-terminated multiple hydrogen bond-reinforced segments, and chain extenders accounts for 25%-40% of the total mass of both the hard segment and soft segment components, thus ensuring that the prepared polyurethane material possesses certain mechanical properties and good biological properties. In this embodiment, the molar ratio of NCO groups to active hydrogen groups in both the hard and soft segment components is 1.01-1.05, wherein the active hydrogen groups include OH and NH2 groups, resulting in a slightly larger amount of NCO groups than OH groups. At the reaction endpoint, the NCO groups and active hydrogen groups react completely.

[0053] This embodiment provides a polyurethane material prepared by the above-described preparation method. This polyurethane material is a polyurethane reinforced with aliphatic diisocyanate-terminated groups containing multiple hydrogen bonds. The multiple hydrogen bonds provide greater strength, compensating for the adverse effects on the material's mechanical properties caused by the introduction of high-silicon segments, while simultaneously ensuring good flexibility.

[0054] This embodiment also provides an application of polyurethane material in medical devices, including vascular stents, artificial blood vessels, cardiac occluders, balloons, or heart valves.

[0055] Example 1

[0056] The preparation method of the polyurethane material in this embodiment is as follows:

[0057] S1: Weigh adipic acid dihydrazide and add it to the reactor. Add dimethylformamide (DMF) and stir to disperse the adipic acid dihydrazide in the DMF. Add isophorone diisocyanate (IPDI) and stir the reaction at 60°C for 60 min under nitrogen protection to obtain IPDI-terminated adipic acid dihydrazide-reinforced segments. The molar ratio of IPDI to adipic acid dihydrazide is 2:1.

[0058] S2: Weigh 1000 molecular weight α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane into a reactor, dehydrate under vacuum at 110℃ for 2 h, lower the temperature to 80℃, add diphenylmethane diisocyanate (MDI), and react for 4 h under nitrogen protection to obtain prepolymerized α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane. The molar ratio of α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane to diphenylmethane diisocyanate is 2:1.

[0059] S3: Poly(1,6-hexyl carbonate) diol with a molecular weight of 2000 and prepolymerized α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane were placed in a reactor and dehydrated under vacuum at 110°C for 2 hours, and then set aside for later use.

[0060] S4: Weigh diphenylmethane diisocyanate (MDI) and IPDI-terminated adipate dihydrazide reinforcing segments, stir and heat to 80°C under nitrogen protection, add dehydrated poly(1,6-hexyl carbonate) diol and dehydrated prepolymer α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane, react for 2 h to obtain the prepolymer.

[0061] S5: Add 1,4-butanediol (BDO) to the prepolymer for chain extension, and react at 120°C for 24 hours to obtain a polyurethane material. This polyurethane material is a polyurethane material modified with multiple hydrogen bonds and enhanced with organosilicon.

[0062] In the above preparation method, the ratio of diphenylmethane diisocyanate to IPDI-terminated adipate dihydrazide reinforced segment is 1:0.2 (molar ratio), and the ratio of poly(1,6-hexyl carbonate) diol to α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane is 3:1 (molar ratio).

[0063] The polyurethane material obtained in this embodiment comprises a hard segment and a soft segment in its main molecular chain. The hard segment is composed of diphenylmethane diisocyanate, IPDI-terminated adipate dihydrazide reinforcing segments, and 1,4-butanediol. The soft segment is composed of poly(1,6-hexyl carbonate) glycol and prepolymerized α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane. The mass of the hard segment components accounts for 30.5% of the total mass of both the hard and soft segment components. The molar ratio of NCO groups to active hydrogen groups in both the hard and soft segment components is 1.01.

[0064] Example 2

[0065] The preparation method of the polyurethane material in this embodiment is as follows:

[0066] S1: Weigh adipic acid dihydrazide and add it to the reactor. Add DMF and stir to disperse the adipic acid dihydrazide in the DMF. Add IPDI and stir the reaction at 60°C for 60 min under nitrogen protection to obtain IPDI-terminated adipic acid dihydrazide-reinforced segments. The molar ratio of IPDI to adipic acid dihydrazide is 2:1.

[0067] S2: Weigh 1000 molecular weight α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane into a reactor, dehydrate under vacuum at 110℃ for 2 h, lower the temperature to 80℃, add MDI, and react for 4 h under nitrogen protection to obtain prepolymerized α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane. The molar ratio of α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane to diphenylmethane diisocyanate is 2:1.

[0068] S3: Poly(1,6-hexyl carbonate) diol with a molecular weight of 2000 and prepolymerized α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane were placed in a reactor and dehydrated under vacuum at 110°C for 2 hours, and then set aside for later use.

[0069] S4: Weigh out MDI and IPDI-terminated adipate dihydrazide reinforcing segments, stir and heat to 80°C under nitrogen protection, add dehydrated poly(1,6-hexyl carbonate) diol and dehydrated prepolymer α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane, react for 2 h to obtain the prepolymer.

[0070] S5: Add BDO to the prepolymer for chain extension and react at 120°C for 24 hours to obtain a polyurethane material, which is a polyurethane material modified with multiple hydrogen bonds and organosilicon.

[0071] In the above preparation method, the ratio of diphenylmethane diisocyanate to IPDI-terminated adipate dihydrazide reinforcing segment is 1:1.25 (molar ratio), and the ratio of poly(1,6-hexyl carbonate) diol to α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane is 3:1 (molar ratio).

[0072] The polyurethane material obtained in this embodiment comprises a hard segment and a soft segment in its main molecular chain. The hard segment is composed of diphenylmethane diisocyanate, IPDI-terminated adipate dihydrazide reinforcing segments, and 1,4-butanediol. The soft segment is composed of poly(1,6-hexyl carbonate) glycol and prepolymerized α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane. The mass of the hard segment components accounts for 34% of the total mass of the hard and soft segment components. The molar ratio of NCO groups to active hydrogen groups in both the hard and soft segment components is 1.01.

[0073] Example 3

[0074] The preparation method of the polyurethane material in this embodiment is as follows:

[0075] S1: Weigh imidazolidinyl urea and add it to the reactor. Add DMF and stir to disperse and suspend the imidazolidinyl urea in the DMF. Add IPDI and stir the reaction at 80°C for 120 min under nitrogen protection to obtain IPDI-terminated imidazolidinyl urea reinforced segments. The molar ratio of IPDI to imidazolidinyl urea is 2:1.

[0076] S2: Weigh 1000 molecular weight α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane into a reactor, dehydrate under vacuum at 120℃ for 2 h, lower the temperature to 80℃, add MDI, and react for 2 h under nitrogen protection to obtain prepolymerized α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane. The molar ratio of α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane to diphenylmethane diisocyanate is 2:1.

[0077] S3: Poly(1,6-hexyl carbonate) diol with a molecular weight of 2000 and prepolymerized α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane were placed in a reactor and dehydrated under vacuum at 120°C for 3 hours, and then set aside for later use.

[0078] S4: Weigh out the MDI and IPDI-terminated imidazolidinyl urea reinforced segments, stir and heat to 80°C under nitrogen protection, add the dehydrated poly(1,6-hexyl carbonate) glycol and the dehydrated prepolymer α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane, react for 2 h to obtain the prepolymer.

[0079] S5: Add BDO to the prepolymer for chain extension and react at 80°C for 48 hours to obtain a polyurethane material, which is a polyurethane material modified with multiple hydrogen bonds and organosilicon.

[0080] In the above preparation method, the ratio of diphenylmethane diisocyanate to IPDI-terminated imidazolidinyl urea reinforced segment is 1:0.8 (molar ratio), and the ratio of poly(1,6-hexyl carbonate) diol to α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane is 1:1 (molar ratio).

[0081] The polyurethane material obtained in this embodiment has a main molecular chain comprising a hard segment and a soft segment. The hard segment is composed of diphenylmethane diisocyanate, IPDI-terminated imidazolidinyl urea reinforcing segments, and 1,4-butanediol. The soft segment is composed of poly(1,6-hexyl carbonate) glycol and prepolymerized α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane. The mass of the hard segment components accounts for 45% of the total mass of both the hard and soft segment components. The molar ratio of NCO groups to active hydrogen groups in both the hard and soft segment components is 1.05.

[0082] Example 4

[0083] The preparation method of the polyurethane material in this embodiment is as follows:

[0084] S1: Weigh adipic acid dihydrazide and add it to the reactor. Add DMF and stir to disperse the adipic acid dihydrazide in the DMF. Add IPDI and stir the reaction at 70°C for 120 min under nitrogen protection to obtain IPDI-terminated adipic acid dihydrazide-reinforced segments. The molar ratio of IPDI to adipic acid dihydrazide is 2:1.

[0085] S2: Weigh 1000 molecular weight bis(hydroxypropyl)polydimethylsiloxane into a reactor, dehydrate under vacuum at 100°C for 4 hours, lower the temperature to 80°C, add MDI, and react for 2 hours under nitrogen protection to obtain prepolymerized bis(hydroxypropyl)polydimethylsiloxane. The molar ratio of bis(hydroxypropyl)polydimethylsiloxane to diphenylmethane diisocyanate is 2:1.

[0086] S3: Place 2000 molecular weight poly(1,6-hexyl carbonate) glycol and prepolymerized bis(hydroxypropyl)polydimethylsiloxane in a reactor and dehydrate them under vacuum at 120°C for 1.5 h for later use.

[0087] S4: Weigh out MDI and IPDI-terminated adipate dihydrazide reinforcing segments, stir and heat to 70°C under nitrogen protection, add dehydrated poly(1,6-hexyl carbonate) glycol and dehydrated prepolymerized bis(hydroxypropyl)polydimethylsiloxane, react for 3 hours to obtain the prepolymer.

[0088] S5: BDO is added to the prepolymer for chain extension, and the reaction is carried out at 100°C for 36 hours to obtain a polyurethane material, which is a polyurethane material modified with multiple hydrogen bonds and organosilicon.

[0089] In the above preparation method, the ratio of diphenylmethane diisocyanate to IPDI-terminated imidazolidinyl urea reinforced segment is 1:0.05 (molar ratio), and the ratio of poly(1,6-hexyl carbonate) diol to α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane is 1:1 (molar ratio).

[0090] The polyurethane material obtained in this embodiment has a main molecular chain comprising a hard segment and a soft segment. The hard segment is composed of diphenylmethane diisocyanate, IPDI-terminated adipate dihydrazide reinforcing segments, and 1,4-butanediol. The soft segment is composed of poly(1,6-hexyl carbonate) glycol and prepolymerized bis(hydroxypropyl)polydimethylsiloxane. The mass of the hard segment components accounts for 30% of the total mass of both the hard and soft segment components. The molar ratio of NCO groups to active hydrogen groups in both the hard and soft segment components is 1.04.

[0091] Example 5

[0092] The preparation method of the polyurethane material in this embodiment is as follows:

[0093] S1: Weigh imidazolidinyl urea and add it to the reactor. Add DMF and stir to disperse the imidazolidinyl urea in the DMF. Add HMDI and stir the reaction at 80°C for 120 min under nitrogen protection to obtain HMDI-terminated imidazolidinyl urea reinforced segments. The molar ratio of HMDI to adipic acid dihydrazide is 2:1.

[0094] S2: Weigh 2000 molecular weight α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane into a reactor, dehydrate under vacuum at 120℃ for 2 h, lower the temperature to 80℃, add naphthalene diisocyanate, and react for 2 h under nitrogen protection to obtain prepolymerized α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane. The molar ratio of α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane to naphthalene diisocyanate is 2:1.

[0095] S3: Poly(1,6-hexyl-1,2-ethyl carbonate) diol with a molecular weight of 2000 and prepolymerized α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane were placed in a reactor and dehydrated under vacuum at 120°C for 3 hours, and then set aside for later use.

[0096] S4: Weigh naphthalene diisocyanate and HMDI-terminated imidazolidinyl urea reinforced segments, stir and heat to 80°C under nitrogen protection, add dehydrated poly(1,6-hexyl-1,2-ethyl carbonate) diol or dehydrated prepolymer α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane in proportion, react for 2 h to obtain the prepolymer.

[0097] S5: Add BDO to the prepolymer for chain extension and react at 80°C for 48 hours to obtain a polyurethane material, which is a polyurethane material modified with multiple hydrogen bonds and organosilicon.

[0098] In the above preparation method, the ratio of naphthalene diisocyanate to HMDI-terminated imidazolidinyl urea reinforced segment is 1:1 (molar ratio), and the ratio of poly(1,6-hexyl carbonate) diol to α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane is 1:2 (molar ratio).

[0099] The polyurethane material obtained in this embodiment has a main molecular chain comprising a hard segment and a soft segment. The hard segment is composed of naphthalene diisocyanate, HMDI-terminated imidazolidinyl urea reinforcing segments, and 1,4-butanediol. The soft segment is composed of poly(1,6-hexyl-1,2-ethyl carbonate) diol and prepolymerized α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane. The mass of the hard segment components accounts for 35% of the total mass of both the hard and soft segment components. The molar ratio of NCO groups to active hydrogen groups in both the hard and soft segment components is 1.02.

[0100] Example 6

[0101] The preparation method of the polyurethane material in this embodiment is as follows:

[0102] S1: Weigh adipic acid dihydrazide and add it to the reactor. Add DMF and stir to disperse the adipic acid dihydrazide in the DMF. Add IPDI and stir the reaction at 70°C for 120 min under nitrogen protection to obtain IPDI-terminated adipic acid dihydrazide-reinforced segments. The molar ratio of IPDI to adipic acid dihydrazide is 2:1.

[0103] S2: Weigh 1000 molecular weight bis(hydroxypropyl)polydimethylsiloxane into a reactor, dehydrate under vacuum at 100°C for 3 hours, lower the temperature to 80°C, add MDI, and react for 2 hours under nitrogen protection to obtain prepolymerized bis(hydroxypropyl)polydimethylsiloxane. The molar ratio of bis(hydroxypropyl)polydimethylsiloxane to diphenylmethane diisocyanate is 2:1.

[0104] S3: Place 2000 molecular weight poly(1,6-hexyl carbonate) glycol or prepolymerized bis(hydroxypropyl)polydimethylsiloxane in a reactor and dehydrate under vacuum at 120°C for 1.5 h, then set aside.

[0105] S4: Weigh out MDI and IPDI-terminated adipate dihydrazide reinforcing segments, stir and heat to 70°C under nitrogen protection, add dehydrated poly(1,6-hexyl carbonate) glycol and dehydrated prepolymerized bis(hydroxypropyl)polydimethylsiloxane, react for 3 hours to obtain the prepolymer.

[0106] S5: Ethylenediamine is added to the prepolymer for chain extension, and the reaction is carried out at 20°C for 4 hours to obtain a polyurethane material, which is a polyurethane material modified with multiple hydrogen bonds and organosilicon.

[0107] In the above preparation method, the ratio of diphenylmethane diisocyanate to IPDI-terminated adipate dihydrazide reinforced segment is 1:0.05 (molar ratio), and the ratio of poly(1,6-hexyl carbonate) diol to bis(hydroxypropyl)polydimethylsiloxane is 1:1 (molar ratio).

[0108] The polyurethane material obtained in this embodiment comprises a hard segment and a soft segment in its main molecular chain. The hard segment is composed of diphenylmethane diisocyanate, IPDI-terminated adipate dihydrazide reinforcing segments, and ethylenediamine. The soft segment is composed of poly(1,6-hexyl carbonate) glycol or prepolymerized bis(hydroxypropyl)polydimethylsiloxane. The mass of the hard segment component accounts for 30% of the total mass of both the hard and soft segment components. The molar ratio of NCO groups to active hydrogen groups in both the hard and soft segment components is 1.04.

[0109] Comparative Example 1 (excluding multiple hydrogen bond-reinforced segments compared to Example 1)

[0110] The preparation method of the polyurethane material in this comparative example is as follows:

[0111] W1: Weigh 1000 molecular weight α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane into a reactor, dehydrate under vacuum at 110℃ for 2 h, lower the temperature to 80℃, add MDI, and react for 4 h under nitrogen protection to obtain prepolymerized α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane. The molar ratio of α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane to diphenylmethane diisocyanate is 2:1.

[0112] W2: Poly(1,6-hexyl carbonate) diol with a molecular weight of 2000 and prepolymerized α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane were placed in reactors and dehydrated under vacuum at 110°C for 2 hours for later use.

[0113] W3: Weigh MDI and heat it to 80°C under nitrogen protection. Add dehydrated poly(1,6-hexyl carbonate) diol and dehydrated prepolymer α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane. React for 2 hours to obtain the prepolymer.

[0114] W4: Adding BDO to the prepolymer as a chain extender and reacting at 120°C for 24 hours yields a polyurethane material.

[0115] In the above preparation method, the ratio of poly(1,6-hexyl carbonate) diol to α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane is 3:1 (molar ratio).

[0116] The polyurethane material obtained in this embodiment has a main molecular chain comprising a hard segment and a soft segment. The hard segment is composed of diphenylmethane diisocyanate and 1,4-butanediol, while the soft segment is composed of poly(1,6-hexyl carbonate) diol and prepolymerized α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane. The mass of the hard segment component accounts for 30.5% of the total mass of both the hard and soft segment components. The molar ratio of NCO groups to active hydrogen groups in both the hard and soft segment components is 1.01.

[0117] Comparative Example 2 (compared to Example 1, the multi-hydrogen bond-enhanced chain segment was added directly to the reactants without isocyanate end-capping, and only multi-hydrogen bond small molecules were used for chain extension)

[0118] The preparation method of the polyurethane material in this comparative example is as follows:

[0119] W1: Weigh 1000 molecular weight α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane into a reactor, dehydrate under vacuum at 110℃ for 2 h, lower the temperature to 80℃, add MDI, and react for 4 h under nitrogen protection to obtain prepolymerized α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane. The molar ratio of α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane to diphenylmethane diisocyanate is 2:1.

[0120] W2: Poly(1,6-hexyl carbonate) diol with a molecular weight of 2000 and prepolymerized α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane were placed in reactors and dehydrated under vacuum at 110°C for 2 hours for later use.

[0121] W3: Weigh MDI and adipic acid dihydrazide, stir and heat to 80°C under nitrogen protection, add dehydrated poly(1,6-hexyl carbonate) diol and dehydrated prepolymer α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane, react for 2 h to obtain the prepolymer.

[0122] W4: Adding BDO to the prepolymer for chain extension and reacting at 120°C for 24 hours yields a polyurethane material.

[0123] In the above preparation method, the ratio of poly(1,6-hexyl carbonate) diol to α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane is 3:1 (molar ratio).

[0124] The polyurethane material obtained in this embodiment comprises a hard segment and a soft segment in its main molecular chain. The hard segment is composed of diphenylmethane diisocyanate, adipate dihydrazide, and 1,4-butanediol, while the soft segment is composed of poly(1,6-hexyl carbonate) diol and prepolymerized α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane. The mass of the hard segment components accounts for 30.5% of the total mass of the hard and soft segment components, and the molar ratio of NCO groups to active hydrogen groups in both components is 1.01.

[0125] Test Example 1

[0126] The mechanical properties of the polyurethane materials prepared in Examples 1-2 and Comparative Examples 1-2 were tested. Tensile strength, elongation at break, and Young's modulus were tested according to the national standard GB / T528-2009, while right-angle tear and trouser tear were tested according to the national standard GB / T529-2008.

[0127] Table 1. Mechanical property test results

[0128]

[0129] As can be seen from the table above, Examples 1-2 exhibit superior overall mechanical properties compared to Comparative Examples 1-2. In Example 1, the tensile strength is only 13 MPa and the right-angle tear strength is only 30 N / mm, compared to Comparative Example 1. Example 1 uses aliphatic diisocyanate-terminated multi-hydrogen-bonded reinforced segments, resulting in superior tensile and tear properties. In Example 2, compared to Comparative Example 1, Comparative Example 2 directly uses multi-hydrogen-bonded small-molecule chain extensions, resulting in similar tensile strength, but a lower trouser-shaped tear strength (6 N / mm), indicating poor notch tear resistance. Furthermore, the excessively high Young's modulus indicates poor material flexibility, making it unsuitable for applications such as heart valves and cardiovascular stents.

[0130] Test Example 2

[0131] The infrared spectra of the polyurethane materials prepared in Examples 1-2 and Comparative Examples 1-2 were tested using the ATR (Total Reflectance Attenuation) method. The test results are as follows: Figure 1 .

[0132] Figure 1 In the infrared spectrum shown, the curves of Examples 1-2 (i.e., curves 3 and 4) are at 3335 cm⁻¹. -1 A single absorption peak with a smaller NH content appears at 2270 cm⁻¹ in the urethane and hydrogen-bonded small molecules, while the double absorption of NH₂ in the used adipic acid dihydrazide completely disappears, indicating that the adipic acid dihydrazide reacts completely with the isocyanate. -1The complete disappearance of the isocyanate peak indicates that the isocyanate has completely reacted. The carbonyl group (C=O) absorption peak in polycarbonate polyols is at 1740 cm⁻¹. -1 The Si-O-Si absorption peak in the organosilicon segment appears at 1020 cm⁻¹. -1 Compared to Comparative Example 1, in Examples 1-2, the absorption peak of the carbon group (C=O) in the carbamate is due to hydrogen bonding. In the comparative example, the absorption peak of the carbon group (C=O) in the carbamate appears at 1705 cm⁻¹. -1 In Examples 1-2, the carbon group (C=O) absorption peak in the carbamate appeared at 1660 cm⁻¹. -1 The presence of this component indicates that the aliphatic diisocyanate-terminated multiple hydrogen-bonded reinforced segments form strong hydrogen bonds in the elastomer. The urethane ester is obtained by reacting phenyl diisocyanate with a polyol.

[0133] Test Example 3

[0134] To investigate the good biocompatibility of the polyurethane material prepared in this invention, an in vitro animal experiment was conducted to compare the polyurethane material of Example 1 and the bovine pericardium material. The polyurethane material obtained in Example 1 and the bovine pericardium were cut into sheets of the same size and implanted into the backs of mice. The calcification of the materials was examined after 8 weeks.

[0135] The test results are shown in Table 2 below:

[0136] Table 2 Results of Calcification Performance Test

[0137]

[0138] The pathological analysis of the tissue staining surrounding the material is shown in the figure below:

[0139] As can be seen from Table 2, the multi-hydrogen bond-reinforced organosilicon-modified polyurethane material prepared in Example 1 has excellent in vivo anti-calcification properties compared with traditional bovine pericardium materials. The synthesized polyurethane material has extremely low calcification, down to as low as 0.01 g / g.

[0140] Figure 2 Pathological analysis of bovine pericardium 8 weeks post-mortem (a / b / c are alizarin red staining, d / e / f are H&E staining). Figure 3 The pathological analysis of the polyurethane material obtained in Example 1 after 8 weeks is shown in the images (a / b / c are Alizarin Red staining, d / e / f are H&E staining). The pathological analysis shows... Figure 2 Numerous plaques were observed at the pericardial implantation site in the calcified bovine pericardium, indicating significant calcification. Figure 3 The polyurethane material obtained in Example 1 showed no patch formation around its periphery, indicating that no calcification occurred. (This is achieved through...) Figure 3As can be seen, there were no obvious inflammatory cells around the polyurethane material obtained in Example 1, indicating that the material is non-cytotoxic. Therefore, compared with traditional bovine pericardium materials, the polyurethane material prepared by this invention has excellent anti-calcification properties and biological properties.

[0141] The above description is merely a preferred 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 scope of the technology 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 method for preparing a polyurethane material, characterized in that, Includes the following steps: S1: Weigh out small molecules with multiple hydrogen bonds, add organic solvent and stir to make the small molecules with multiple hydrogen bonds dispersed and suspended in the organic solvent, add aliphatic diisocyanate, and stir and react at 40-80℃ for 0.5-4h under nitrogen protection to obtain aliphatic diisocyanate-terminated multiple hydrogen bond-enhanced segments. S2: Weigh hydroxyl-terminated polydimethylsiloxane, dehydrate it under vacuum at 100-130℃ for 1-3 hours, lower the temperature to 60-80℃, add phenyl diisocyanate, and react at 60-80℃ for 2-4 hours under nitrogen protection to obtain prepolymerized hydroxyl-terminated polydimethylsiloxane. S3: Dehydrate the polyol and the prepolymerized hydroxyl-terminated polydimethylsiloxane respectively; S4: Weigh the phenyl diisocyanate and the aliphatic diisocyanate end-capped multiple hydrogen bond reinforced segments, stir and heat under nitrogen protection, add the dehydrated polypolyol and the dehydrated prepolymerized hydroxyl-terminated polydimethylsiloxane, and react to obtain the prepolymer. S5: Add a chain extender to the prepolymer and react to obtain the polyurethane material, wherein the polyurethane material is a polyurethane material modified with multiple hydrogen bonds and enhanced with organosilicon.

2. The method for preparing the polyurethane material as described in claim 1, characterized in that, The multiple hydrogen-bonded small molecules include oxalic acid dihydrazide, succinic acid dihydrazide, adipic acid dihydrazide, imidazolidinyl urea, or ureidopyrimidinone.

3. The method for preparing the polyurethane material as described in claim 1, characterized in that, The fatty diisocyanates include hexamethylene diisocyanate (HDI), isophorone diisocyanate (IPDI), dicyclohexylmethane diisocyanate (HMDI), or lysine diisocyanate (LDI).

4. The method for preparing the polyurethane material as described in claim 1, characterized in that, The molecular formula of the aliphatic diisocyanate-terminated multihydrogen bond-reinforced segment is formula (1) or formula (2): R1 is an aliphatic segment, and R2 is a segment containing multiple hydrogen bonds.

5. The method for preparing the polyurethane material as described in claim 1, characterized in that, The polypolyols include one or more of the following: poly(1,6-hexyl carbonate) diol, poly(1,6-hexyl-1,2-ethyl carbonate) diol, poly(1,8-octanediol carbonate) diol, poly(1,10-decanediol carbonate) diol, polytetrahydrofurandiol, poly(1,6-hexanediol), poly(1,8-octanediol), and poly(1,10-decanediol).

6. The method for preparing the polyurethane material according to claim 1, characterized in that, The terminal hydroxyl polydimethylsiloxane includes one or more of bis(hydroxypropyl)polydimethylsiloxane, α,ω-bis(hydroxyethoxypropyl)polydimethylsiloxane, and bis(hydroxybutyl)polydimethylsiloxane.

7. The method for preparing the polyurethane material according to claim 1, characterized in that, The phenyl diisocyanate includes one or more of toluene diisocyanate (TDI), diphenylmethane diisocyanate (MDI), and naphthalene diisocyanate (NDI).

8. The method for preparing the polyurethane material according to claim 1, characterized in that, The polyurethane material includes a hard segment and a soft segment. The hard segment is composed of at least the phenyl diisocyanate, the aliphatic diisocyanate-terminated multiple hydrogen bond-reinforced segments, and the chain extender. The soft segment is composed of at least the polyol and the prepolymerized hydroxyl-terminated polydimethylsiloxane. The mass of the phenyl diisocyanate, the aliphatic diisocyanate-terminated multiple hydrogen bond-reinforced segments, and the chain extender accounts for 25%-40% of the total mass of the components of the hard segment and the soft segment.

9. A polyurethane material, characterized in that, The polyurethane material is prepared by any one of the preparation methods described in claims 1 to 8.

10. An application of the polyurethane material as described in claim 9 in a medical device, said medical device comprising a vascular stent, an artificial blood vessel, a cardiac occluder, a balloon, or a heart valve.

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