Polysiloxane polycarbonate type polyurethane elastomer containing aromatic disulfide bond and sulphobetaine as well as preparation method and application of polysiloxane polycarbonate type polyurethane elastomer

Abstract

The invention discloses a polysiloxane polycarbonate type polyurethane elastomer containing aromatic disulfide bonds and sulphobetaine as well as a preparation method and application of the polysiloxane polycarbonate type polyurethane elastomer. The elastomer is prepared from polycarbonate diol, amino-terminated polydimethylsiloxane, diisocyanate, a first chain extender, a second chain extender and a first catalyst. The problem that a traditional polyurethane material is poor in calcification resistance, oxidative degradation resistance and thrombus resistance is solved, the material has better physical and mechanical properties while having the self-healing capacity, and the long-term stability of the material serving as a medical implant material in application can be improved.

Description

Technical Field

[0001] This invention belongs to the field of medical implant materials technology of synthetic polymers, specifically relating to a polysiloxane polycarbonate type polyurethane elastomer containing aromatic disulfide bonds and sulfobetaine, its preparation method and application. Background Technology

[0002] Polyurethane (PU) consists of three main building blocks: diols or polyols, diisocyanates, and chain extenders. PU encompasses a wide range of materials composed of various combinations of these three building blocks. Diisocyanates and chain extenders form the hard segments (HS) of PU, while the polyols form the soft segments (SS). The chemical incompatibility between these hard and soft segments determines the microphase separation structure of polyurethane materials. This structure enables PU to be used in numerous industrial applications. PU possesses high modulus and tensile strength, toughness, elasticity, good tear strength, and abrasion resistance. It is adaptable to a wide variety of polymer processing technologies, and its extensive formulation options allow for performance tailored to specific applications. Major industrial applications of PU include flexible and rigid foams in the automotive and furniture industries, thermoplastic elastomers for footwear, coatings, adhesives, and sealants.

[0003] The wide range of mechanical properties and good biocompatibility of polyurethane (PU) have led to its various applications in biomedicine, such as in vascular grafts, catheters, breast implant shells, artificial heart diaphragms, heart valves, and drug delivery systems. However, in the late 1980s, it was discovered that PU pacemaker insulator leads and breast implant shells showed signs of failure due to degradation caused by the bio-environment. This failure was likely closely related to the oxidative degradation of the polyether soft segments, highlighting some of its limitations in the biomedical field.

[0004] Meanwhile, the calcification problem of PU materials in the blood environment also greatly limits their application. Although some researchers have participated in the development of effective anti-calcification pretreatment methods to reduce the calcification rate of these materials, the problem has not been completely eradicated. It can only alleviate calcium phosphate deposition in the short term, and the long-term stability of implantation is therefore difficult to guarantee.

[0005] In environments where implanted materials need to come into direct contact with blood, the hydrophobic surface of unmodified PU materials is difficult to form polar interactions with water, making proteins more prone to adsorption and aggregation on its surface. Therefore, prolonged contact can easily lead to thrombosis. While techniques such as surface coating with heparin can achieve anti-thrombotic effects, these coatings are difficult to chemically bond with the polymer, and thus their anti-thrombotic effect will still be lost within a short period.

[0006] The application environment of implanted materials is often a dynamic environment, and various complex motion processes may occasionally leave various minor damages and cracks in the materials. The presence of these damages and cracks can easily lead to stress concentration in the materials, and thus premature failure.

[0007] Research on the use of PU in long-term medical implants continues, given its excellent properties. While the aforementioned problems can often be solved individually, or even only temporarily, by various methods such as heparin coating, ensuring that PU materials possess sufficient strength and flexibility, and are protected from damage such as oxidative degradation, calcification, thrombosis, and stress concentration after implantation, remains a major challenge for the successful implantation of PU materials in biological systems.

[0008] Patent CN116178666A discloses a polysiloxane polyurethane elastomer containing multiple hydrogen bonds, which has achieved good results in improving the mechanical properties, resistance to oxidative degradation, and biological stability of PU materials. However, the hydrophobic nature of the material itself may still not prevent problems such as thrombosis at the implantation site after long-term implantation. Summary of the Invention

[0009] The primary objective of this invention is to overcome the shortcomings of the prior art and provide a method for preparing a polysiloxane polycarbonate type polyurethane elastomer containing aromatic disulfide bonds and sulfobetaine.

[0010] Another objective of this invention is to provide a polysiloxane polycarbonate type polyurethane elastomer containing aromatic disulfide bonds and sulfobetaine obtained by the above preparation method. This aims to solve the problem of the performance and long-term stability that current polyurethane materials cannot meet in the blood environment, so that the polyurethane material has excellent mechanical properties as well as anti-calcification, anti-oxidative degradation, anti-protein non-specific adsorption ability and self-healing properties, making it a medical implant material that can exist stably in the body for a long time.

[0011] Another object of the present invention is to provide the application of the above-mentioned polysiloxane polycarbonate type polyurethane elastomer containing aromatic disulfide bonds and sulfobetaine in the preparation of medical materials.

[0012] To achieve the above objectives, the present invention adopts the following technical solution:

[0013] A method for preparing a polysiloxane polycarbonate type polyurethane elastomer containing aromatic disulfide bonds and sulfobetaine includes the following steps:

[0014] S1: Dehydrate polycarbonate diol and amino-terminated polydimethylsiloxane;

[0015] S2: In an anhydrous and oxygen-free environment, the dehydrated polycarbonate diol, diisocyanate and the first catalyst are subjected to a first prepolymerization reaction in an organic solvent to obtain the first prepolymer;

[0016] S3: Add dehydrated amino-terminated polydimethylsiloxane to the first prepolymer to carry out a second prepolymerization reaction to obtain the second prepolymer;

[0017] S4: Add the first chain extender and the second chain extender to the second prepolymer to carry out a chain extension reaction, and obtain a polysiloxane polycarbonate type polyurethane elastomer containing aromatic disulfide bonds and sulfobetaine.

[0018] In step S1:

[0019] The polycarbonate diol is preferably polytetramethylene carbonate diol (PCDL); more preferably, it is polytetramethylene carbonate diol with a molecular weight range of 2500-4000 g / mol.

[0020] The polytetramethylene carbonate diol is prepared by the following steps: using diethyl carbonate (DEC) and 1,4-butanediol (BDO) as raw materials, nitrogen gas is introduced and the mixture is stirred. The reaction is carried out under the action of a third catalyst to obtain a crude product, which is then distilled under reduced pressure to obtain polytetramethylene carbonate diol.

[0021] The diethyl carbonate is preferably added after 1,4-butanediol and tetrabutyl titanate; more preferably, it is added dropwise.

[0022] The preferred conditions for adding the drops are 140–160°C and 25–35 drops / min; more preferably, 150°C and 30 drops / min.

[0023] The third catalyst is preferably tetrabutyl titanate.

[0024] The amount of the third catalyst is 0.3-0.5% (w / w) of the total mass of the reactants; more preferably, it is 0.5% (w / w) of the total mass of the reactants. In this invention, the reactants refer to the components that undergo the reaction to form the product, excluding the catalyst and the organic solvent used as a medium.

[0025] The 1,4-butanediol and the diethyl carbonate are preferably mixed in a molar ratio of 1:1.1 to 1.3.

[0026] The stirring speed is preferably 100-300 rpm; more preferably 200 rpm.

[0027] The preferred reaction conditions under the action of the third catalyst are to react at 140-160°C for 2-6 hours and then at 150-180°C for 1-3 hours; more preferably, to react at 150°C for 4 hours and then at 170°C for 2 hours.

[0028] The preferred amino-terminated polydimethylsiloxane (PDMS-NH2) is a polydimethylsiloxane with a molecular weight range of 2500 to 4000 g / mol.

[0029] The aforementioned amino-terminated polydimethylsiloxane is prepared by the following steps: octamethylcyclotetrasiloxane (D4) and 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane (AMM) are mixed, nitrogen gas is introduced, and the mixture is stirred. The mixture is reacted under the action of a second catalyst to obtain a crude product. The crude product is then distilled under reduced pressure to obtain amino-terminated polydimethylsiloxane.

[0030] The second catalyst is preferably tetramethylammonium hydroxide pentahydrate.

[0031] The amount of the second catalyst is 0.3 to 0.5% (w / w) of the total mass of the reaction components; more preferably, it is 0.5% (w / w) of the total mass of the reaction components.

[0032] The 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane and the octamethylcyclotetrasiloxane are preferably in a molar ratio of 1:(7.6-12.6).

[0033] The stirring speed is preferably 100-300 rpm; more preferably 200 rpm.

[0034] The preferred reaction conditions under the action of the second catalyst are to react at 80-100°C for 10-15 hours and then at 130-170°C for 1-4 hours; more preferably, to react at 90°C for 12 hours and then at 150°C for 2 hours.

[0035] The preferred conditions for vacuum distillation are rotary distillation at 130–170°C for 1–4 hours; more preferably, rotary distillation at 150°C for 2 hours.

[0036] The dehydration is preferably carried out at 80-120°C with reduced pressure rotary evaporation for 0-2 hours; more preferably at 100°C with reduced pressure rotary evaporation for 1 hour.

[0037] In step S2:

[0038] The diisocyanate is preferably at least one of isophorone diisocyanate, hexamethylene diisocyanate, and diphenylmethane-4,4'-diisocyanate; more preferably isophorone diisocyanate.

[0039] The first catalyst is preferably at least one of pentamethyldiethylenetriamine, dibutyltin dilaurate, N,N-dimethylcyclohexylamine, and an organobismuth catalyst; more preferably, it is dibutyltin dilaurate.

[0040] The amount of the first catalyst is preferably calculated as 0.3 to 0.5% of the total mass of the reaction components; more preferably, it is calculated as 0.5% of the total mass of the reaction components.

[0041] The organic solvent is preferably at least one of N,N-dimethylamide, N,N-dimethylacetamide and tetrahydrofuran; more preferably tetrahydrofuran.

[0042] The amount of organic solvent used is preferably 1500-2500% (v / w) of the total mass of the reactants; more preferably 2000% (v / w) of the total mass of the reactants.

[0043] The first prepolymerization reaction is preferably carried out under anhydrous and oxygen-free conditions at 55–60°C for 3–6 hours; more preferably, it is carried out under anhydrous and oxygen-free conditions at 60°C for 3 hours.

[0044] In step S3:

[0045] The molar ratio of the total active groups in the diamino-terminated polydimethylsiloxane and polycarbonate diol to the isocyanate groups in the diisocyanate is preferably 1:(1.1-3); more preferably 1:3.

[0046] The preferred molar ratio of the polycarbonate diol to the diamino-terminated polydimethylsiloxane is (4-1):1.

[0047] The second prepolymerization reaction is preferably carried out under anhydrous and oxygen-free conditions at 55-60°C for 3-6 hours; more preferably, it is carried out under anhydrous and oxygen-free conditions at 60°C for 3 hours.

[0048] In step S4:

[0049] The first chain extender is preferably at least one of 2,2'-diaminodiphenyl disulfide, 2,2'-dithiosalicylic acid and bis(4-hydroxyphenyl) disulfide; more preferably 2,2'-diaminodiphenyl disulfide.

[0050] The second chain extender is preferably sulfobetaine, or a complex of at least one of N-methyldiethanolamine, 1,2-ethylene glycol, 1,4-butanediol, 3-methyl-1,5-pentanediol, 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane with sulfobetaine.

[0051] The sulfobetaine was prepared by the following method: using N-methyldiethanolamine and 1,3-propanesulfonic acid lactone as raw materials, nitrogen gas was introduced and stirred, and the ring-opening reaction was carried out in tetrahydrofuran solvent at high temperature. After depressurization and rotary evaporation, washing and drying, sulfobetaine was obtained.

[0052] The preferred mass ratio of the N-methyldiethanolamine to the 1,3-propanesulfonic acid lactone is (1-2):(1-2); more preferably, it is 1.19:1.22.

[0053] The amount of tetrahydrofuran used is preferably calculated based on a mass-volume ratio of 1,3-propanesulfonic acid lactone to tetrahydrofuran of (0.1-1):1 (g:mL); more preferably based on a mass-volume ratio of 1,3-propanesulfonic acid lactone to tetrahydrofuran of 0.244:1 (g:mL).

[0054] The stirring speed is preferably 100-300 rpm; more preferably 200 rpm.

[0055] The preferred reaction conditions are 50–70°C for 10–14 h; more preferably, 60°C for 12 h.

[0056] The reagent used in the washing process is preferably dichloromethane.

[0057] The molar ratio of the active groups in the diamino-terminated polydimethylsiloxane, the active groups in the polycarbonate diol, the active groups in the diisocyanate, and the total active groups in the first chain extender and the second chain extender is preferably 1:(1-4):(4-15):(2-10); more preferably 1:(1-4):(6-15):(4-10).

[0058] The active group in the aforementioned double-terminated amino polydimethylsiloxane refers to an amino group.

[0059] The active group in the polycarbonate diol refers to the hydroxyl group.

[0060] The active group in the diisocyanate refers to the isocyanate group.

[0061] The active groups of the first and second chain extenders refer to at least one of amino and hydroxyl groups.

[0062] The preferred molar ratio of the active groups of the first chain extender and the second chain extender is (4-0.5):1.

[0063] The chain extension reaction is preferably carried out under anhydrous and oxygen-free conditions at 25–60°C for 6–12 hours; more preferably, it is carried out under anhydrous and oxygen-free conditions at 25°C for 3 hours, followed by anoxic conditions at 60°C for 3 hours.

[0064] The oxygen-free conditions described in this invention are achieved by filling the container with an inert protective gas, N2.

[0065] A polysiloxane polycarbonate type polyurethane elastomer containing aromatic disulfide bonds and sulfobetaine is obtained by the above preparation method.

[0066] The above-mentioned polysiloxane polycarbonate type polyurethane elastomers containing aromatic disulfide bonds and sulfobetaine are used in medical materials.

[0067] The medical materials include medical implant materials, which include artificial blood vessels, visceral stents, or artificial heart valves.

[0068] The technical solution of this invention has the following advantages:

[0069] (1) This invention uses diisocyanate and chain extender as the hard segment structure of polyurethane, and polycarbonate diol and amino-terminated polydimethylsiloxane as the soft segment structure of polyurethane. The introduction of sulfobetaine into the hard segment of polyurethane improves the hydrophilicity of the polyurethane, as the soft segments are all hydrophobic, thus reducing the probability of non-specific protein adsorption in the blood environment and better inhibiting thrombus formation. This solves the technical problem of this invention, enabling it to maintain long-term stability in application.

[0070] (2) This invention employs a higher molar ratio of polycarbonate diol to diamino-terminated polysiloxane, allowing polycarbonate diol to act as a solubilizing segment between the soft and hard segments of polyurethane, thereby reducing the damage to the aggregation state of the hard segments caused by the introduction of sulfobetaine. Furthermore, the use of higher molecular weights of polycarbonate diol and diamino-terminated polysiloxane improves the phase separation between the soft and hard segments of the polyurethane, resulting in better mechanical properties.

[0071] (3) In this invention, aromatic disulfide bonds are introduced into the hard segment of polyurethane. The introduction of this dynamic bond enables the polyurethane material to achieve a certain degree of self-healing, avoiding damage and failure caused by micro-cracks during material movement. Furthermore, the presence of benzene rings endows the polyurethane material with stronger tensile strength, tear strength and other mechanical properties.

[0072] (4) The raw materials of polysiloxane polycarbonate type polyurethane supramolecular elastomer provided by the present invention are inexpensive and the preparation method is simple and easy to implement; the self-made double-terminated amino polydimethylsiloxane and polycarbonate diol are easy to control their molecular weight, which facilitates the control of the internal structure and practical performance of the material.

[0073] (5) The presence of polydimethylsiloxane in the polyurethane raw material provided by the present invention greatly improves the anti-calcification performance of polyurethane materials as medical implant materials, further enhancing the biostability of polyurethane. Furthermore, the terminal amino groups of polydimethylsiloxane result in a certain amount of urea bonds within the polyurethane, making the hard segment structure of polyurethane more prone to aggregation. The presence of polycarbonate diol provides sufficient mechanical and dynamic properties for the polyurethane material.

[0074] (6) Compared with existing silicone polyurethane, the polyurethane provided by the present invention can be better applied to the field of long-term implantable medical materials, such as artificial blood vessels, artificial heart valves, artificial valve stents, and various interventional catheters. Attached Figure Description

[0075] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0076] Figure 1 This is a flowchart illustrating the synthesis of the polysiloxane polycarbonate elastomer containing aromatic disulfide bonds and sulfobetaine prepared in a specific embodiment of the present invention.

[0077] Figure 2 The infrared spectra of the polysiloxane polycarbonate type polyurethane elastomers containing aromatic disulfide bonds and sulfobetaine obtained in Examples 1-6 of the present invention are shown.

[0078] Figure 3 The image shows the GPC diagrams of the polysiloxane polycarbonate type polyurethane elastomers containing aromatic disulfide bonds and sulfobetaine obtained in Examples 1-6 of this invention.

[0079] Figure 4 The bar chart shows the platelet adhesion data of the polysiloxane polycarbonate polyurethane elastomer containing aromatic disulfide bonds and sulfobetaine obtained in Examples 1-6 of this invention; where Control represents PP plastic film.

[0080] Figure 5 This is a bar chart showing the protein adsorption data of the polysiloxane polycarbonate-type polyurethane elastomers containing aromatic disulfide bonds and sulfobetaine obtained in Examples 1-6 of this invention. Detailed Implementation

[0081] The following embodiments are provided to better understand the present invention and are not limited to the preferred embodiments described. They do not constitute a limitation on the content and scope of protection of the present invention. Any product that is the same as or similar to the present invention, derived by any person under the guidance of the present invention or by combining the features of the present invention with other prior art, falls within the protection scope of the present invention.

[0082] For experiments where specific steps or conditions are not specified, the procedures and conditions described in the literature within this field can be followed. Reagents or instruments whose manufacturers are not specified are all commercially available standard products.

[0083] The preparation process of the double-amino-terminated polydimethylsiloxane in a specific embodiment of the present invention is as follows:

[0084]

[0085] Octamethylcyclotetrasiloxane (D4), 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane (AMM), and tetramethylammonium hydroxide pentahydrate (TMAH) were added to a 500 mL three-necked flask. The system was purged with nitrogen for protection and mechanically stirred at 200 rpm. After reacting at 90 °C for 12 h, the temperature was raised to 150 °C to decompose the catalyst and the reaction was maintained at this temperature for 2 h to obtain the crude product. The crude product was then removed by rotary evaporation at 150 °C under reduced pressure for 2 h. After the monomers reacted, the product diamino-terminated polydimethylsiloxane (PDMS-NH2) was obtained, wherein the molar ratio of 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane to octamethylcyclotetrasiloxane was 1:(7.6–12.6); the catalyst TMAH was added at a mass ratio of 0.5% (w / w) of the raw materials (octamethylcyclotetrasiloxane and 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane). When the AMM:D4 molar ratio was 1:7.6, the molecular weight of PDMS-NH2 was 2500 g / mol; when the AMM:D4 molar ratio was 1:12.6, the molecular weight of PDMS-NH2 was 4000 g / mol; and when the AMM:D4 molar ratio was 1:6, the molecular weight of PDMS-NH2 was 2000 g / mol.

[0086] The preparation process of polytetramethylene carbonate diol in a specific embodiment of the present invention is as follows:

[0087]

[0088] 1,4-Butanediol (BDO) and tetrabutyl titanate (TBT) were added to a 500 mL three-necked flask, mechanically stirred at 200 rpm, and purged with nitrogen and refluxed. The temperature was raised to 150 °C. Diethyl carbonate (DEC) was then added dropwise to a round-bottom flask at a rate of 30 drops / min via a constant-pressure burette. After 4 h, the temperature was raised to 170 °C and reacted for 2 h. Low-boiling substances were then removed by rotary evaporation to obtain polytetramethylene carbonate diol (PCDL), wherein the molar ratio of 1,4-butanediol to diethyl carbonate was 1:(1.1–1.4); TBT was added at 0.5% (w / w) of the raw materials (1,4-butanediol and diethyl carbonate). When the molar ratio of BDO to DEC is 1:1.1, a PCDL with a molecular weight of 4000 g / mol is obtained; when the molar ratio of BDO to DEC is 1:1.3, a PCDL with a molecular weight of 2500 g / mol is obtained; and when the molar ratio of BDO to DEC is 1:1.4, a PCDL with a molecular weight of 2000 g / mol is obtained.

[0089] The preparation process of the chain extender sulfobetaine in a specific embodiment of the present invention is as follows:

[0090]

[0091] 11.9 g of N-methyldiethanolamine (MDEA), 12.2 g of 1,3-propanesulfonic acid lactone, and 50 mL of tetrahydrofuran (THF) were added to a three-necked flask. The mixture was mechanically stirred at 200 rpm under nitrogen protection and refluxed. The temperature was raised to 60 °C and refluxed for 12 h. After depressurization and rotary evaporation, the product was washed with dichloromethane. It was then dried in a vacuum oven to obtain the chain extender sulfobetaine (SB).

[0092] Example 1

[0093] This embodiment provides a polysiloxane polycarbonate polyurethane elastomer (TPU) containing aromatic disulfide bonds and sulfobetaine, the preparation process of which is as follows: Figure 1 As shown, the specific preparation method is as follows:

[0094] Polytetramethylene carbonate diol and diamino-terminated polydimethylsiloxane were dehydrated by rotary evaporation at 100°C under reduced pressure for 1 hour. In a glove box filled with inert protective gas N2, polytetramethylene carbonate diol (PCDL), isophorone diisocyanate, and dibutyltin dilaurate were first dissolved in a three-necked flask containing tetrahydrofuran solvent and prepolymerized at 60°C for 3 hours. Then, diamino-terminated polydimethylsiloxane (PDMS-NH2) was added at 60°C and the reaction was continued for another 3 hours. Finally, the temperature was lowered to 25°C and the first chain extender 2,2'-diaminodiphenyl disulfide and the second chain extender sulfobetaine were added and the reaction was continued for 3 hours. The temperature was then raised to 60°C and the reaction was continued for another 3 hours. After the reaction was completed, the product was poured into a container and placed in an oven to evaporate the tetrahydrofuran solvent, thus obtaining a polyurethane elastomer film.

[0095] The molecular weight of both polytetramethylene carbonate glycol and diamino-terminated polydimethylsiloxane is 4000 g / mol. The molar ratio of polytetramethylene carbonate glycol to diamino-terminated polydimethylsiloxane is 4:1. The molar ratio of the active groups (amino) in the diamino-terminated polydimethylsiloxane, the active groups (hydroxy) in the polytetramethylene carbonate glycol, the isocyanate groups in isophorone diisocyanate, and the active groups of the chain extender is [missing information]. The molar ratio of the active groups of 2,2'-diaminodiphenyl disulfide (active group is amino) and sulfobetaine (active group is hydroxyl) is 4:1; the mass of dibutyltin dilaurate accounts for 0.5 wt% of the mass of all reactants (excluding tetrahydrofuran); the amount of tetrahydrofuran solvent accounts for 2000% (v / w) of the raw material mass; the resulting polysiloxane polycarbonate type polyurethane elastomer containing aromatic disulfide bonds and sulfobetaine is designated as TPU1.

[0096] Example 2

[0097] This embodiment provides a polysiloxane polycarbonate type polyurethane elastomer containing aromatic disulfide bonds and sulfobetaine, and its preparation process is as follows: Figure 1 As shown, the preparation method is the same as in Example 1, except that the molar ratio of the active groups of 2,2'-diaminodiphenyl disulfide and sulfobetaine is 3:2, resulting in a polysiloxane polycarbonate type polyurethane elastomer containing aromatic disulfide bonds and sulfobetaine, denoted as TPU2.

[0098] Example 3

[0099] This embodiment provides a polysiloxane polycarbonate type polyurethane elastomer containing aromatic disulfide bonds and sulfobetaine, and its preparation process is as follows: Figure 1 As shown, the preparation method is the same as in Example 1, except that the molar ratio of the active groups of 2,2'-diaminodiphenyl disulfide and sulfobetaine is 2:3, resulting in a polysiloxane polycarbonate elastomer containing aromatic disulfide bonds and sulfobetaine, denoted as TPU3.

[0100] Example 4

[0101] This embodiment provides a polysiloxane polycarbonate type polyurethane elastomer containing aromatic disulfide bonds and sulfobetaine, and its preparation process is as follows: Figure 1 As shown, the preparation method is the same as in Example 1, except that the molar ratio of polytetramethylene carbonate diol and diamino-terminated polydimethylsiloxane is 2:1, and the molar ratio of the active group (amino) in diamino-terminated polydimethylsiloxane, the active group (hydroxy) in polytetramethylene carbonate diol, the isocyanate group in isophorone diisocyanate, and the active group of the chain extender is 1:2:9:6. The resulting polysiloxane polycarbonate type polyurethane elastomer containing aromatic disulfide bonds and sulfobetaine is designated as TPU4.

[0102] Example 5

[0103] This embodiment provides a polysiloxane polycarbonate type polyurethane elastomer containing aromatic disulfide bonds and sulfobetaine, and its preparation process is as follows: Figure 1 As shown, the preparation method is the same as in Example 1, except that the molar ratio of polytetramethylene carbonate diol and diamino-terminated polydimethylsiloxane is 1:1, and the molar ratio of the active group (amino) in diamino-terminated polydimethylsiloxane, the active group (hydroxy) in polytetramethylene carbonate diol, the isocyanate group in isophorone diisocyanate, and the active group of the chain extender is 1:1:6:4. The resulting polysiloxane polycarbonate type polyurethane elastomer containing aromatic disulfide bonds and sulfobetaine is designated as TPU5.

[0104] Example 6

[0105] This embodiment provides a polysiloxane polycarbonate type polyurethane elastomer containing aromatic disulfide bonds and sulfobetaine, and its preparation process is as follows: Figure 1 As shown, the preparation method is the same as in Example 1, except that the molecular weight of polytetramethylene carbonate diol is 2500 g / mol and the molecular weight of dimethylsiloxane with amino-terminated ends is 2500 g / mol; the resulting polysiloxane polycarbonate type polyurethane supramolecular elastomer is designated as TPU6.

[0106] Comparative Example 1

[0107] This comparative example provides an elastomer that differs from Example 1 in that it does not contain the first and second chain extenders. The specific preparation method is as follows:

[0108] Polytetramethylene carbonate diol and diamino-terminated polydimethylsiloxane were dehydrated by rotary evaporation at 100°C under reduced pressure for 1 hour. In a glove box filled with inert protective gas N2, polytetramethylene carbonate diol (PCDL), isophorone diisocyanate, and dibutyltin dilaurate were first dissolved in a three-necked flask containing tetrahydrofuran solvent and prepolymerized at 60°C for 3 hours. Then, diamino-terminated polydimethylsiloxane (PDMS-NH2) was added at 25°C and reacted for another 3 hours. The temperature was then raised to 60°C and the reaction continued for another 3 hours. After the reaction was completed, the product was poured into a container and placed in an oven to evaporate the tetrahydrofuran solvent, thus obtaining a polyurethane elastomer film.

[0109] The molecular weight of polytetramethylene carbonate diol was 4000 g / mol, and the molecular weight of diamino-terminated polydimethylsiloxane was 4000 g / mol; the molar ratio of polytetramethylene carbonate diol to diamino-terminated polydimethylsiloxane was 4:1; the molar ratio of the total active groups in diamino-terminated polydimethylsiloxane and polytetramethylene carbonate diol to the isocyanate groups in isophorone diisocyanate was 1:1.1; the mass of dibutyltin dilaurate accounted for 0.5 wt% of the mass of all reactants (excluding tetrahydrofuran); the amount of tetrahydrofuran solvent accounted for 2000% (v / w) of the raw material mass; and the resulting polysiloxane polycarbonate type polyurethane supramolecular elastomer was designated as Comparative Example 1.

[0110] Comparative Example 2

[0111] This comparative example provides an elastomer that differs from Example 1 in that the second chain extender is 1,4-butanediol. The specific preparation method is as follows:

[0112] Polytetramethylene carbonate diol and diamino-terminated polydimethylsiloxane were dehydrated by rotary evaporation at 100°C under reduced pressure for 1 hour. In a glove box filled with inert protective gas N2, polytetramethylene carbonate diol (PCDL), isophorone diisocyanate, and dibutyltin dilaurate were first dissolved in a three-necked flask containing tetrahydrofuran solvent and prepolymerized at 60°C for 3 hours. Then, diamino-terminated polydimethylsiloxane (PDMS-NH2) was added at 60°C and reacted for another 3 hours. Finally, the temperature was lowered to 25°C and the first chain extender 2,2'-diaminodiphenyl disulfide and the second chain extender 1,4-butanediol were added and reacted for 3 hours. The temperature was then raised to 60°C and the reaction was continued for another 3 hours. After the reaction was completed, the product was poured into a container and placed in an oven to evaporate the tetrahydrofuran solvent, resulting in a polyurethane elastomer film.

[0113] The molecular weight of polytetramethylene carbonate diol was 4000 g / mol, and the molecular weight of diamino-terminated polydimethylsiloxane was 4000 g / mol; the molar ratio of polytetramethylene carbonate diol to diamino-terminated polydimethylsiloxane was 4:1; the molar ratio of the active group (amino) in diamino-terminated polydimethylsiloxane, the active group (hydroxy) in polytetramethylene carbonate diol, the isocyanate group in isophorone diisocyanate, and the active group of the chain extender was 1:4:15:10; the molar ratio of the active groups of 2,2'-diaminodiphenyl disulfide (active group is amino) and 1,4-butanediol (active group is hydroxy) was 4:1; the mass of dibutyltin dilaurate accounted for 0.5 wt% of the mass of all reactants (excluding tetrahydrofuran); the amount of tetrahydrofuran solvent accounted for 2000% (v / w) of the raw material mass; the resulting polysiloxane polycarbonate type polyurethane supramolecular elastomer was designated as Comparative Example 2.

[0114] Comparative Example 3

[0115] This comparative example provides an elastomer that differs from Example 1 in that the first chain extender is replaced with ureidinium pyrimidinone, the molecular weight of polytetramethylene carbonate glycol is changed to 2000 g / mol, the molecular weight of diamino-terminated polydimethylsiloxane is changed to 2000 g / mol, the molar ratio of polytetramethylene carbonate glycol to diamino-terminated polydimethylsiloxane is 1:3; the molar ratio of the total active groups in diamino-terminated polydimethylsiloxane and polytetramethylene carbonate glycol, the isocyanate groups of isophorone diisocyanate, and the active groups of the chain extender is 1:1.5:0.5; the molar ratio of the active groups of the first chain extender ureidinium pyrimidinone (hydroxyl) to the second chain extender sulfobetaine (hydroxyl) is 1:4. The specific preparation method is as follows:

[0116] Polytetramethylene carbonate diol and diamino-terminated polydimethylsiloxane were dehydrated by rotary evaporation at 100°C under reduced pressure for 1 hour. In a glove box filled with inert protective gas N2, polytetramethylene carbonate diol, isophorone diisocyanate, and dibutyltin dilaurate were dissolved in a three-necked flask containing tetrahydrofuran solvent and prepolymerized at 60°C for 3 hours. Then, diamino-terminated polydimethylsiloxane (PDMS-NH2) was added at 60°C and the reaction was continued for another 3 hours. Finally, the temperature was lowered to 25°C, and the first chain extender, ureidopyrimidinone, and the second chain extender, sulfobetaine, were added and the reaction was continued for 3 hours. The temperature was then raised to 60°C and the reaction was continued for another 3 hours. After the reaction was completed, the product was poured into a container and placed in an oven to evaporate the tetrahydrofuran solvent, thus obtaining a polyurethane elastomer film.

[0117] The tetramethylene carbonate diol has a molecular weight of 2000 g / mol, and the diamino-terminated polydimethylsiloxane has a molecular weight of 2000 g / mol; the molar ratio of polytetramethylene carbonate diol to diamino-terminated polydimethylsiloxane is 1:3; the molar ratio of the total active groups in diamino-terminated polydimethylsiloxane and polytetramethylene carbonate diol, the isocyanate groups in isophorone diisocyanate, and the active groups in the chain extender is 1:1.5:0.5; the molar ratio of the active groups in the first chain extender, ureidopyrimidinone, and the second chain extender, sulfobetaine, is 1:4; the mass of dibutyltin dilaurate accounts for 0.5 wt% of the mass of all reactants (excluding tetrahydrofuran); the amount of tetrahydrofuran solvent accounts for 2000% (v / w) of the raw material mass; the resulting polysiloxane polycarbonate type polyurethane supramolecular elastomer is designated as Comparative Example 3.

[0118] Experimental Example 1

[0119] The elastomers obtained in Examples 1-6 were tested.

[0120] (1) Infrared testing: Select an infrared spectrometer with attenuated total reflectance (ATR) accessory, and use zinc selenide (ZnSe) with a refractive index of 2.4 as the infrared transmitting material. During the test, first place the ATR accessory in the optical path of the infrared spectrometer and scan the air background. Then, place the sample surface to be tested in close contact with the infrared transmitting crystal surface of the ATR accessory and scan to obtain the infrared spectrum of the sample surface to be tested.

[0121] (2) GPC test: Tetrahydrofuran was used as the mobile phase, the flow rate was 1.0 mL / min, the test column temperature was 40℃, the detector temperature was 35℃, and monodisperse polystyrene was used as the standard sample to determine the molecular weight and distribution of supramolecular elastomer.

[0122] (3) Platelet adhesion test: Cut the PP plastic film and polyurethane elastomer samples into 7mm×7mm sizes, clean them with purified water, soak them in PBS buffer for 30min, dry them, and put them into dry clean test tubes. Add 500 μL of platelet-rich plasma (PRP) to each tube using a pipette, immerse the sample, and incubate at 37°C for 45 min. Then, remove the sample with tweezers and gently rinse it in 0.9% NaCl solution to remove platelets that are not adhering to the material surface. Transfer the sample to a clean centrifuge tube containing 250 μL of 2.5% glutaraldehyde, immerse the sample for 6 h, discard the waste liquid, and rinse three times with 0.9% NaCl. After drying the sample with cold air, add 100 μL of Rhodamine 123 staining solution to the surface of each sample, ensuring the staining solution completely covers the sample surface. Incubate at 37°C in the dark for 20 min. After staining, wash the sample surface three times with 0.9% NaCl solution, dry the sample, and observe the platelet adhesion under a fluorescence microscope. Randomly observe the images of each sample in different regions and manually count the platelets.

[0123] (4) Protein adsorption test: Prepare 200 μg / mL BSA solution and 0.01 M, pH 7.4 PBS buffer, and cut each sample into 1×1 cm pieces. 2 The sample was placed in a test tube containing an appropriate amount of PBS solution and incubated at 37°C for 30 min. After drying the sample surface, it was immersed in a test tube containing 1.5 mL of 200 μg / mL BSA solution and incubated at 37°C with shaking at 100 rpm for 3 h. The sample was then removed and rinsed three times in 1.5 mL of PBS solution to collect any unadsorbed protein. The PBS solution used for rinsing was combined with the BSA solution after sample adsorption. 1 mL of the mixed solution was added to 4 mL of Coomassie Brilliant Blue staining solution. After standing for 10 min, the absorbance was measured at 595 nm using a UV spectrophotometer. This absorbance was used as the absorbance of the BSA solution after sample adsorption, with PBS solution as a blank reference. The concentration was determined according to the standard curve.

[0124] (5) Self-healing efficiency: First, a dumbbell-shaped sample of a specific size was prepared from the dried polyurethane film using a cutting knife. Then, the polyurethane film sample was cut with a clean razor blade. Then, a certain force was used to bring the fracture surfaces of the two half films into close contact. After that, it was transferred to a 60℃ constant temperature oven for 12 hours. The strain recovery was quantitatively evaluated by general tensile tests at different time periods. The self-healing efficiency was defined as: tensile strength after repair / tensile strength before repair × 100%.

[0125] Experimental Example 2

[0126] The mechanical properties of the elastomers obtained in Examples 1-6 and Comparative Examples 1-3 were tested using the test methods in GB / T528-2009. The test results are shown in Table 1.

[0127] Table 1. Mechanical property results of the embodiments and comparative examples.

[0128] Tensile strength (MPa) Elongation at break (%) Self-healing efficiency (%) TPU1 39.4 1981 78.3 TPU2 37.1 1734 73.4 TPU3 31.7 1684 63.1 TPU4 34.9 1763 76.8 TPU5 27.7 1208 77.6 TPU6 36.3 1898 71.4 Comparative Example 1 21.6 1735 24.4 Comparative Example 2 30.4 1615 21.8 Comparative Example 3 25.4 1461 31.3

[0129] As can be seen from Examples 1-6 and Comparative Examples 1-3, when the molar ratio of the first chain extender 2,2'-diaminodiphenyl disulfide and the second chain extender sulfobetaine is higher than 2:3, and the molar ratio of polytetramethylene carbonate glycol to diamino-terminated polydimethylsiloxane is higher than 2:1, the tensile strength and repair rate are both higher than those of Comparative Examples 1-3. Comparative Example 3 is a sample of polysiloxane polyurethane elastomer disclosed in patent CN116178666A, in which the second chain extender was replaced with sulfobetaine. Its mechanical properties are not ideal and are weaker than those of Examples 1-6 of this invention. It can be seen that the introduction of the first and second chain extenders and the adjustment of the proportions of each component can give polyurethane materials excellent mechanical properties. The FT-IR spectra of Examples 1-6 of this invention are as follows: Figure 2 As shown, from Figure 2 The data shows the correspondence between the infrared characteristic peaks of polyurethane elastomers with different structures and the predicted products. The above data proves that the present invention has synthesized products with the target structure.

[0130] The GPC spectra of Examples 1-6 of this invention are as follows: Figure 3 As shown in Table 2, the results of Examples 1-6 were obtained by comparing with the standard curve:

[0131] Table 2 GPC test results of Examples 1-6

[0132]

[0133]

[0134] The data in Table 2 show that the number-average molecular weights of Examples 1-6 of the present invention are all around 4 × 10⁻⁶. 4 above.

[0135] The platelet adhesion data of Examples 1-6 and Comparative Example 2 of this invention are as follows: Figure 4 As shown, from Figure 4 As can be seen from the present invention, the synthesized polyurethane elastomers all have low platelet adsorption values, making them suitable as medical implant materials.

[0136] The protein adsorption data of Examples 1-6 and Comparative Example 2 of this invention are as follows: Figure 5 As shown, from Figure 5It can be seen that Examples 1-6, which contain a sulfobetaine structure in the main chain, have better resistance to non-specific protein adsorption than Comparative Example 2, which does not contain a sulfobetaine structure.

[0137] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. A method for preparing a polysiloxane polycarbonate type polyurethane elastomer containing aromatic disulfide bonds and sulfobetaine, characterized in that, The preparation steps include the following: S1: Dehydrate polycarbonate diol and amino-terminated polydimethylsiloxane; S2: In an anhydrous and oxygen-free environment, the dehydrated polycarbonate diol, diisocyanate and the first catalyst are subjected to a first prepolymerization reaction in an organic solvent to obtain the first prepolymer; S3: Add dehydrated amino-terminated polydimethylsiloxane to the first prepolymer to carry out a second prepolymerization reaction to obtain the second prepolymer; S4: Add the first chain extender and the second chain extender to the second prepolymer to carry out a chain extension reaction, and obtain a polysiloxane polycarbonate type polyurethane elastomer containing aromatic disulfide bonds and sulfobetaine. The first chain extender is at least one of 2,2'-diaminodiphenyl disulfide, 2,2'-dithiosalicylic acid and bis(4-hydroxyphenyl) disulfide; The second chain extender is sulfobetaine, or a complex of at least one of N-methyldiethanolamine, 1,2-ethylene glycol, 1,4-butanediol, 3-methyl-1,5-pentanediol, and 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane with sulfobetaine.

2. The preparation method according to claim 1, characterized in that: The polycarbonate diol is polytetramethylene carbonate diol; The diisocyanate is at least one of isophorone diisocyanate, hexamethylene diisocyanate, and diphenylmethane-4,4'-diisocyanate; The first catalyst is at least one of pentamethyldiethylenetriamine, dibutyltin dilaurate, N,N-dimethylcyclohexylamine, and an organobismuth catalyst; The organic solvent is at least one of N,N-dimethylamide, N,N-dimethylacetamide, and tetrahydrofuran; The aforementioned amino-terminated polydimethylsiloxane is an amino-terminated polydimethylsiloxane with a molecular weight range of 2500–4000 g / mol.

3. The preparation method according to claim 2, characterized in that: The polycarbonate diol is polytetramethylene carbonate diol with a molecular weight range of 2500-4000 g / mol; The diisocyanate mentioned is isophorone diisocyanate; The first catalyst is dibutyltin dilaurate; The organic solvent is tetrahydrofuran; The first chain extender is 2,2'-diaminodiphenyl disulfide.

4. The preparation method according to claim 1, characterized in that: The amount of the first catalyst is calculated as 0.3 to 0.5% of the total mass of the reaction components; The volumetric amount of the organic solvent used is 1500-2500% of the total mass of the reactants; The molar ratio of the total active groups in the diamino-terminated polydimethylsiloxane and polycarbonate diol to the isocyanate groups in the diisocyanate is 1:(1.1-3). The molar ratio of the polycarbonate diol to the amino-terminated polydimethylsiloxane is (4-1):1; The molar ratio of the active groups in the diamino-terminated polydimethylsiloxane, the active groups in the polycarbonate diol, the active groups in the diisocyanate, and the total active groups in the first chain extender and the second chain extender is 1:(1-4):(4-15):(2-10). The molar ratio of the active groups of the first chain extender and the second chain extender is (4-0.5):

1.

5. The preparation method according to claim 1, characterized in that: The dehydration process involves rotary evaporation at 80–120°C under reduced pressure for 0–2 hours. The first prepolymerization reaction is carried out under anhydrous and oxygen-free conditions at 55-60°C for 3-6 hours. The second prepolymerization reaction is carried out under anhydrous and oxygen-free conditions at 55–60°C for 3–6 hours. The chain extension reaction is carried out under anhydrous and oxygen-free conditions at 25–60°C for 6–12 hours. The aforementioned oxygen-free conditions are achieved by filling the gas with inert protective gas N2.

6. The preparation method according to claim 1, characterized in that: The polytetramethylene carbonate diol is prepared by the following steps: using diethyl carbonate and 1,4-butanediol as raw materials, nitrogen gas is introduced, stirring is performed, and the reaction is carried out under the action of a third catalyst to obtain a crude product, which is then distilled under reduced pressure to obtain polytetramethylene carbonate diol. The amino-terminated polydimethylsiloxane is prepared by the following steps: octamethylcyclotetrasiloxane and 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane are mixed, nitrogen gas is introduced, and the mixture is stirred. The mixture is reacted under the action of a second catalyst to obtain a crude product. The crude product is then distilled under reduced pressure to obtain the amino-terminated polydimethylsiloxane. The sulfobetaine is prepared by the following steps: using N-methyldiethanolamine and 1,3-propanesulfonic acid lactone as raw materials, nitrogen gas is introduced and stirred, and the ring-opening reaction is carried out in tetrahydrofuran solvent at high temperature. After depressurization and rotary evaporation, washing and drying, sulfobetaine is obtained.

7. The preparation method according to claim 6, characterized in that: In the preparation steps of the polytetramethylene carbonate diol: The diethyl carbonate is added after 1,4-butanediol and tetrabutyl titanate; The third catalyst is tetrabutyl titanate; The amount of the third catalyst used is 0.3 to 0.5% (w / w) of the mass of the reaction components; The 1,4-butanediol and the diethyl carbonate are mixed in a molar ratio of 1:1.1 to 1.3; In the preparation steps of the aforementioned amino-terminated polydimethylsiloxane: The second catalyst is tetramethylammonium hydroxide pentahydrate; The amount of the second catalyst is 0.3 to 0.5% (w / w) of the mass of the reaction components; The 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane and the octamethylcyclotetrasiloxane are mixed in a molar ratio of 1:(7.6-12.6); In the preparation step of the sulfobetaine described above: The mass ratio of N-methyldiethanolamine to 1,3-propanesulfonic acid lactone is (1-2):(1-2); The amount of tetrahydrofuran used is calculated based on a mass-volume ratio of 1,3-propanesulfonic acid lactone to tetrahydrofuran of (0.1-1):1 (g:mL); The reagent used for the washing process is dichloromethane.

8. The preparation method according to claim 6, characterized in that: In the preparation steps of the polytetramethylene carbonate diol: The reaction conditions are as follows: react at 140–160°C for 2–6 hours, followed by reacting at 150–180°C for 1–3 hours. In the preparation steps of the aforementioned amino-terminated polydimethylsiloxane: The reaction conditions are as follows: react at 80-100℃ for 10-15 hours, followed by reacting at 130-170℃ for 1-4 hours. The conditions for vacuum distillation are rotary distillation at 130–170°C for 1–4 hours; In the preparation step of the sulfobetaine described above: The reaction is carried out at 50–70°C for 10–14 hours.

9. A polysiloxane polycarbonate type polyurethane elastomer containing aromatic disulfide bonds and sulfobetaine, characterized in that: It is obtained by the preparation method according to any one of claims 1 to 8.

10. The application of the polysiloxane polycarbonate type polyurethane elastomer containing aromatic disulfide bonds and sulfobetaine as described in claim 9 in medical materials.

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