Polyurethane composition and preparation method and application thereof

Abstract

The present application relates to a polyurethane composition, comprising 10 to 150 parts of polysiloxane, 10 to 150 parts of a first polyol, 50 to 400 parts of an isocyanate compound, 0 to 0.5 parts of a catalyst, 10 to 150 parts of a second polyol, 0.5 to 8 parts of a polyhydroxy tertiary amine, and 10 to 60 parts of a small molecule siloxane, wherein the molecular weight of the polysiloxane is 200Da to 20000Da, and the end is an active hydrogen functional group, the first polyol comprises 20 to 100% of a polymer polyol and 0 to 60% of a small molecule polyol, and one end of the small molecule siloxane end is an active hydrogen functional group, and the other end is three identical alkoxy groups connected to silicon. The polyurethane composition of the present application can be used to prepare a medical material for promoting tissue repair, has high biological safety, good compatibility with different tissues, good mechanical flexibility, fast and efficient bonding, and high adhesion, and can promote good tissue healing.

Description

Technical Field

[0001] The present application relates to the field of biomedical technology, and in particular to a polyurethane composition and a preparation method and application thereof. Background Art

[0002] In medicine, wound healing is usually promoted by suturing or using staplers, which is not only complicated but also easy to cause secondary damage to the wound, causing great pain to the patient. Medical adhesives for tissue adhesion are an excellent alternative to surgical sutures and staplers. They are easy to operate, less harmful, and can promote wound healing.

[0003] Common medical adhesives include acrylates, biologically extracted proteins and polyurethanes. The adhesive strength of adhesives composed of acrylates is too strong, difficult to peel off, and easy to cause skin damage. The raw materials of biologically extracted proteins are difficult to obtain and cannot meet the needs of industrial production. Polyurethane (PU) is an organic polymer material containing a carbamate structure (-NH-COO-) in the molecular chain. It has suitable viscosity and is easy to prepare, but the water resistance, mechanical strength and other properties of polyurethane adhesives still need to be improved. In addition, compared with conventional adhesives, medical adhesives also need to have good tissue compatibility in order to promote tissue healing, regeneration and repair. Summary of the invention

[0004] Based on this, the purpose of this application includes providing a polyurethane composition that has no solvent addition, high biosafety, good compatibility with different tissues, good mechanical flexibility, fast and efficient bonding and high adhesion, can provide a wet healing environment, is degradable and the degradation products can promote good tissue healing.

[0005] The first aspect of the present application provides a polyurethane composition, comprising the following raw material components in parts by weight: 10 to 150 parts of polysiloxane, 10 to 150 parts of a first polyol, 50 to 400 parts of an isocyanate compound, 0 to 0.5 parts of a catalyst, 5 to 60 parts of a second polyol, 0.5 to 8 parts of a polyhydroxy tertiary amine, and 10 to 60 parts of a small molecule siloxane;

[0006] Wherein, the polysiloxane meets the following characteristics: (a1) the molecular weight is 200Da to 20000Da; (a2) the end is capped with an active hydrogen functional group;

[0007] The first polyol comprises: 20% to 100% of a polymer polyol, the molecular weight of the polymer polyol is 600Da to 10000Da, and 0 to 30% of a small molecule polyol, the molecular weight of the small molecule polyol is 40Da to 500Da;

[0008] The isocyanate compound meets the following characteristics: (b1) a molecular weight of 60Da to 800Da; (b2) an average functionality of 2 to 4;

[0009] The second polyol includes the polymer polyol and / or the small molecule polyol;

[0010] The polyhydroxy tertiary amine meets the following characteristics: (c1) a molecular weight of 60Da to 500Da; (c2) an average functionality of 2 to 4;

[0011] The small molecule siloxane meets the following characteristics: (d1) the molecular weight is 100Da to 1000Da; (d2) one of the end caps directly connected to silicon is an active hydrogen functional group, and the other three ends directly connected to silicon are the same alkoxy groups.

[0012] The first polyol comprises 20% to 100% of a polymer polyol, the molecular weight of the polymer polyol is 600Da to 10000Da, and 0 to 30% of a small molecule polyol, the molecular weight of the small molecule polyol is 40Da to 500Da;

[0013] In some embodiments of the present application, in the polyurethane composition, the active hydrogen functional group includes a hydroxyl group, a thiol group, an amino group, a carboxyl group or a combination thereof.

[0014] In some embodiments of the present application, in the polyurethane composition, the small molecule polyol in the first polyol and the small molecule polyol in the second polyol are independently selected from: glycerol, ethylene glycol, 1,4-butanediol, 1,6-hexanediol, 1,8-octanediol or a combination thereof;

[0015] The polymer polyol in the first polyol and the polymer polyol in the second polyol are independently selected from: polyether polyol, polyester polyol, polyglycerol or a combination thereof.

[0016] In some embodiments of the present application, in the polyurethane composition, the polyvalent hydroxy tertiary amine includes triethanolamine, triisopropanolamine, N-methyldiethanolamine, N-ethyldiethanolamine, N-n-propyldiethanolamine, tert-butyldiethanolamine, N-ethyldiethanolamine, 3-dimethylamino-1-propanol, N,N-dimethylisopropanolamine, 4-hydroxy-1-methylhexahydroazepine or a combination thereof.

[0017] In some embodiments of the present application, in the polyurethane composition, the isocyanate compound includes hexamethylene diisocyanate, 4,4-bis(isocyanate cyclohexyl)methane, toluene cyclohexylene diisocyanate, 2,2,4-trimethylhexane diisocyanate, L-lysine diisocyanate, 2,6-diisocyanate methyl hexanoate, isophorone diisocyanate or a combination thereof.

[0018] In some embodiments of the present application, in the polyurethane composition, the small molecule siloxane includes mercapto-terminated trimethoxysilane, mercapto-terminated triethoxysilane, hydroxyl-terminated trimethoxysilane, hydroxyl-terminated triethoxysilane, amino-terminated trimethoxysilane, amino-terminated triethoxysilane or a combination thereof.

[0019] In some embodiments of the present application, in the polyurethane composition, the catalyst includes an organic tin catalyst, an organic bismuth catalyst, an amine catalyst or a combination thereof.

[0020] The second aspect of the present application provides a method for preparing a polyurethane composition, comprising the following steps:

[0021] Providing various raw materials according to the definition of the polyurethane composition provided in the first aspect of the present application;

[0022] The polysiloxane, the first polyol and the isocyanate compound are mixed, the catalyst is added, and a prepolymerization reaction is carried out under a protective gas atmosphere to obtain a prepolymer;

[0023] Mixing the prepolymer, the second polyol and the polyhydroxy tertiary amine, and performing a chain extension reaction under a protective gas atmosphere; and

[0024] The small molecule siloxane is added to the product of the chain extension reaction to carry out reaction.

[0025] In some embodiments of the present application, the preparation method has one or more of the following technical features:

[0026] (e1) The prepolymerization reaction conditions include: heating at 50°C to 90°C;

[0027] (e2) The conditions of the chain extension reaction include: heating at 50° C. to 90° C.;

[0028] (e3) In the step of adding small molecule siloxane to react, the reaction conditions include: heating at 40°C to 120°C.

[0029] The third aspect of the present application provides the use of the polyurethane composition provided in the first aspect of the present application or the polyurethane composition prepared by the preparation method of the second aspect of the present application in the preparation of medical materials for promoting tissue repair.

[0030] The polyurethane composition of the present application has a multi-crosslinked bonding structure, and the formation of the multi-crosslinked system is based on a large number of hydrogen bonds generated by each raw material in the reaction, micro-crosslinking of silanol hydrolysis bonding, and the bond reaction of isocyanate groups. The bonding reaction of isocyanate groups includes -NCO hydrolysis to produce amino groups, amino groups reacting with unhydrolyzed -NCO, -NCO reacting with amino groups, thiol groups, carboxyl groups, etc. on the skin, and -NCO reacting with silanol groups generated after siloxane hydrolysis. The polyurethane composition of the present application has strong adhesion to human tissue in a wet state, but will not damage the tissue.

[0031] The preparation method of the present application uses appropriate reaction conditions to subject the raw materials to a series of reactions including prepolymerization, chain extension and end-capping to form a multiple cross-linking system. No organic solvent is added, and the method has high biosafety, simple operation and wide applicability.

[0032] The polyurethane composition of the present application has suitable viscosity, good mechanical flexibility after curing, fast and efficient bonding and high adhesion, and the modulus can be adjusted as needed to make it compatible with a variety of tissues.

[0033] The polyurethane composition of the present application can provide a wet healing environment, can be degraded and the degraded substances are beneficial to wound healing, and can be used to prepare medical materials that promote tissue wound healing, inhibit scars, etc. DETAILED DESCRIPTION

[0034] The present application will be further described below in conjunction with the embodiments and examples. It should be understood that these examples are only used to illustrate the present application and are not intended to limit the scope of the present application. In addition, it should be understood that after reading the content taught in the present application, those skilled in the art may make various changes or modifications to the present application, and these equivalent forms also fall within the protection scope of the claims attached to the present application.

[0035] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this application belongs. The terms used herein in the specification of this application are only for the purpose of describing specific embodiments and are not intended to limit this application.

[0036] the term

[0037] Unless otherwise specified or incompatible herewith, the terms and phrases used herein shall have the following meanings:

[0038] In the present application, the selection scope of "and / or" includes any one of two or more related listed items, and also includes any and all combinations of the related listed items, wherein the any and all combinations include any two related listed items, any more related listed items, or a combination of all related listed items.

[0039] In the present application, the terms "preferred", "preferable", "better", etc. are only used to describe implementation methods or examples with better effects. It should be understood that they do not constitute limitations on the scope of protection of the present application.

[0040] In the present application, "further", "further", "particularly" and the like are used for descriptive purposes to indicate differences in content, but should not be construed as limiting the scope of protection of the present application.

[0041] In the present application, the terms "first", "second", "third", etc. in "the first aspect", "the second aspect", "the third aspect", etc. are used only for descriptive purposes and cannot be understood as indicating or implying relative importance or quantity, nor can they be understood as implicitly indicating the importance or quantity of the indicated technical features. Moreover, "first", "second", "third", etc. only serve the purpose of non-exhaustive enumeration and description, and it should be understood that they do not constitute a closed limitation on quantity.

[0042] In the present application, the technical features described in an open manner include closed technical solutions composed of the listed features, and also include open technical solutions containing the listed features.

[0043] In the present application, when it comes to numerical intervals (i.e., numerical ranges), unless otherwise specified, the optional numerical distribution is considered continuous within the above numerical interval, and includes the two numerical endpoints (i.e., the minimum and maximum values) of the numerical range, and each numerical value between the two numerical endpoints. Unless otherwise specified, when the numerical interval only refers to integers within the numerical interval, it includes the two endpoint integers of the numerical range, and each integer between the two endpoints. In addition, when multiple ranges are provided to describe features or characteristics, these ranges can be combined. In other words, unless otherwise specified, the ranges disclosed herein should be understood to include any and all subranges included therein.

[0044] The temperature parameters in this application, unless otherwise specified, are allowed to be either constant temperature treatment or to vary within a certain temperature range. It should be understood that the constant temperature treatment allows the temperature to fluctuate within the accuracy range controlled by the instrument. Fluctuations within the range of ±5°C, ±4°C, ±3°C, ±2°C, and ±1°C are allowed.

[0045] In the present application, weight may be μg, mg, g, kg or other mass units known in the chemical industry.

[0046] In the present application, unless otherwise specified, the molecular weight refers to the average molecular weight, and further, unless otherwise specified, refers to the weight average molecular weight.

[0047] The compounds and their abbreviations involved in the present application include: polydimethylsiloxane (PDMS), polylactic acid (PLG), hexamethylene diisocyanate (HDI), polycaprolactone (PCL), L-lysine diisocyanate (LDI), and polypropylene glycol (PPG).

[0048] In the present application, polyisocyanate refers to an isocyanate compound containing two or more active sites in the molecule, which can extend to the active groups at both ends to form a linear polymer, or cross-link to form a (stereo) polymer by multi-directional polymerization along the active groups during polymerization.

[0049] In the first aspect of the present application, a polyurethane composition is provided, which has no organic solvent added, high biological safety, strong adhesion, and is degradable. The degradation products include small molecule silicones, which have the effect of promoting wound healing and can be used to prepare biomedical materials such as medical adhesives.

[0050] The raw materials for preparing the polyurethane composition of the present application include: siloxane compounds (polysiloxane, small molecule siloxane), polyols (first polyol, second polyol), isocyanate compounds, catalysts (can be used for prepolymerization) and polyhydroxy tertiary amines. Each component undergoes a series of reactions to form a special cross-linking system, which provides more hydrogen bonding sites, so that the composition has strong adhesion in a wet state.

[0051] Furthermore, the polysiloxane includes the following features: (a1) a molecular weight of 200Da to 20000Da; (a2) end-capped with an active hydrogen functional group. In the present application, the active hydrogen functional group may be a hydroxyl group, a thiol group, an amino group, a carboxyl group or a combination thereof.

[0052] In some embodiments, the polysiloxane may be any one or a combination of several active hydrogen-terminated polysiloxanes, such as dual-terminated hydroxyl polysiloxane, dual-terminated amino polysiloxane, dual-terminated mercapto polysiloxane, dual-terminated carboxyl polysiloxane or a combination thereof.

[0053] Further, the first polyol includes the following characteristics: (b1) includes at least 20 parts of a polymer polyol, the molecular weight of the polymer polyol is 600Da to 10000Da; (b2) includes 0 to 30 parts of a small molecule polyol, the molecular weight of the small molecule polyol is 40Da to 500Da. In this application, the meaning of "poly" is at least two, such as two, three, etc., and the meaning of "multiple" is at least two, such as two, three, etc., unless otherwise clearly and specifically defined. The small molecule polyol in this application refers to a polyol having the following characteristics: having multiple (such as at least 2) hydroxyl groups, a small molecular weight (such as 60 to 500Da), and no repeated structural units, and the repeated structural units refer to repeating units formed by more than 10 alkylene groups. The polyols of suitable types and proportions in this application can adjust the modulus of the polyurethane composition, give it more hydrogen bonding sites, change the crosslinking density, and adjust the degradation rate.

[0054] In some embodiments, the small molecule polyol may be glycerol, ethylene glycol, 1,4-butanediol, 1,6-hexanediol, 1,8-octanediol, or a combination thereof.

[0055] In some embodiments, the polymer polyol may be a polyether polyol, a polyester polyol, a polyglycerol, or a combination thereof.

[0056] Furthermore, the polyether polyol may be polytetramethylene glycol polyol, polypropylene glycol polyol, polyethylene glycol polyol, polypropylene glycol-ethylene glycol polyol, polytetramethylene glycol-butylene glycol polyol or a combination thereof.

[0057] Further, the polyester polyol may be poly(ε-caprolactone) polyol, polycarbonate polyol, polyglycolic acid, polylactic acid, poly(lactide-glycolide) polyol or a combination thereof.

[0058] Furthermore, the isocyanate compound includes the following characteristics: (c1) a molecular weight of 60Da to 800Da; (c2) an average functionality of 2 to 4. In the present application, the average functionality refers to: the ratio of the number of functional groups that can actually participate in the reaction to the total amount of monomers in the reaction system in the linear polycondensation stage before reaching the gel point in a mixed polycondensation or co-polycondensation reaction with two or more monomers.

[0059] In some embodiments, the sum of the number of terminal active hydrogen functional groups of the starting reaction raw material polyol is 1, and the number of isocyanate functional groups is 2.2 to 6, and can further be 3 to 5.

[0060] In some embodiments, the isocyanate compound can be hexamethylene diisocyanate, 4,4-bis(isocyanate cyclohexyl)methane, toluene cyclohexylene diisocyanate, 2,2,4-trimethylhexane diisocyanate, L-lysine diisocyanate, 2,6-diisocyanate methyl hexanoate, isophorone diisocyanate or a combination thereof.

[0061] Furthermore, the second polyol includes a small molecule polyol and / or a polymer polyol.

[0062] In some embodiments, the second polyol may be a small molecule polyol, and further, may be glycerol, ethylene glycol, 1,4-butanediol, 1,6-hexanediol, 1,8-octanediol, or a combination thereof.

[0063] In some embodiments, the polyhydroxy tertiary amine includes triethanolamine, triisopropanolamine, N-methyldiethanolamine, N-ethyldiethanolamine, N-n-propyldiethanolamine, tert-butyldiethanolamine, N-ethyldiethanolamine, 3-dimethylamino-1-propanol, N,N-dimethylisopropanolamine, 4-hydroxy-1-methylhexahydroazepine, or a combination thereof.

[0064] In some embodiments, the catalyst includes an organotin catalyst, an organobismuth catalyst, an amine catalyst, or a combination thereof.

[0065] Further, the small molecule siloxane includes the following characteristics: (d1) the molecular weight is 100Da to 1000Da; (d2) one of the end caps directly connected to silicon is an active hydrogen functional group, and the other three ends directly connected to silicon are the same alkoxy groups. Further, the number of carbon atoms in the alkoxy group is 1 to 4, for example, the alkoxy group can be methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, etc.

[0066] In some embodiments, the small molecule siloxane can be mercapto-terminated trimethoxysilane, mercapto-terminated triethoxysilane, hydroxyl-terminated trimethoxysilane, hydroxyl-terminated triethoxysilane, amino (primary and secondary amine)-terminated trimethoxysilane, amino (primary and secondary amine)-terminated triethoxysilane, or a combination thereof.

[0067] In the present application, small molecule siloxane is further reacted with the prepolymer (having -NCO end capping) to introduce small molecule siloxane, so that the composition can undergo reversible hydrolysis and condensation in a wet state.

[0068] The polyurethane composition of the present application is a solvent-free polymer material, and no organic solvent is required in the preparation process. It has high biological safety and strong environmental protection.

[0069] In some embodiments, the polyurethane composition includes the following components in parts by weight: 10 to 150 parts of polysiloxane, 10 to 150 parts of a first polyol, 50 to 400 parts of an isocyanate compound, 0 to 0.5 parts of a catalyst, 10 to 150 parts of a second polyol, 0.5 to 8 parts of a polyhydroxy tertiary amine, and 10 to 60 parts of a small molecule siloxane. Wherein, the weight proportion of polysiloxane can be independently 10 to 150 parts, further can be 50 to 120 parts, and the weight proportions are exemplified as 10, 30, 50, 60, 70, 80, 90, 100, 110, 150, etc.; the weight proportion of the first polyol can be independently 10 to 150 parts, further can be 20 to 60 parts, and the weight proportions are exemplified as 20, 30, 40, 50, 60, etc.; the weight proportion of the isocyanate compound can be independently 50 to 400 parts, further can be 100 to 200 parts, and the weight proportions are exemplified as 100, 110, 130, 140, 150, 160, 180, 200, etc.; the weight proportion of the catalyst can be independently 0 to 0 .5 parts, can further be 0.02-0.08 parts, exemplified by weight such as 0, 0.02, 0.03, 0.05, 0.08, 0.1, 0.3, 0.5, etc.; the weight parts of the second polyol can independently be 5-60 parts, can further be 5-15 parts, exemplified by weight such as 5, 8, 10, 12, 15, etc.; the weight parts of the polyhydroxy tertiary amine can independently be 0.5-8 parts, can further be 2-6 parts, exemplified by weight such as 0.5, 2, 3, 4, 5, 6, 8, etc.; the weight parts of the small molecule siloxane can independently be 10-60 parts, can further be 10-40, exemplified by weight such as 10, 20, 25, 30, 35, 40, etc.

[0070] In a second aspect of the present application, a method for preparing a polyurethane composition is provided, by which the composition can achieve multiple cross-linking bonds, adjustable modulus and multi-scenario mechanical applicability, and the multiple cross-linking includes a large number of hydrogen bonds existing in the polyurethane system, micro-cross-linking of silanol hydrolysis bonds, and isocyanate group reaction bonds (referring to the hydrolysis of NCO to produce amino groups, which then react with other NCOs, or the reaction of NCO with amino groups, thiol groups, carboxyl groups, etc. on the skin, and the reaction of NCO with silanol groups produced by the hydrolysis of siloxane).

[0071] In some embodiments, the method for preparing the polyurethane composition comprises the following steps:

[0072] According to the first aspect of the present application, various raw materials are provided, and some of the raw materials are subjected to dehydration pretreatment as required;

[0073] The polysiloxane, the first polyol and the isocyanate compound are mixed, a catalyst is optionally added, and prepolymerized under a protective gas atmosphere to obtain a prepolymer;

[0074] Mixing the prepolymer, the second polyol and the polyhydroxy tertiary amine, and performing chain extension under a protective gas atmosphere; and

[0075] Add small molecule siloxane to react.

[0076] Dehydration pretreatment can improve the efficiency of polymerization reaction, promote the reaction, enhance the mechanical properties of polymer, etc. For some raw materials that are easy to absorb water, dehydration can be performed before the reaction. For example, siloxane compounds (polysiloxane, small molecule siloxane), polyhydroxy tertiary amines and polyols (first polyol, second polyol) can be pretreated optionally. In some embodiments, the dehydration pretreatment method includes: treating at 80°C to 150°C and -0.100Mpa to -0.098Mpa for 2h to 4h.

[0077] In some embodiments, the polysiloxane and the first polyol are subjected to a dehydration pretreatment. Further, the dehydration pretreatment comprises heating at a vacuum degree of -0.100 MPa to -0.098 MPa and 80°C to 150°C. Further, the heating time is 2h to 4h.

[0078] In some embodiments, the polyhydroxy tertiary amine and the second polyol are subjected to dehydration pretreatment. Further, the dehydration pretreatment method includes heating at a vacuum degree of -0.100Mpa to -0.098Mpa and 80°C to 150°C. Further, the heating time is 2h to 4h.

[0079] In some embodiments, the small molecule siloxane is subjected to a dehydration pretreatment. Further, the dehydration pretreatment comprises heating at a vacuum degree of -0.100 MPa to -0.098 MPa and 80° C. to 150° C., and further, the heating time is 2 h to 4 h.

[0080] In some embodiments, the prepolymerization reaction conditions include heating at 50° C. to 90° C. Further, the reaction time is 4 h to 8 h.

[0081] In some embodiments, the chain extension reaction conditions include heating at 50° C. to 90° C. Further, the reaction time is 4 h to 8 h.

[0082] In some embodiments, in the step of adding small molecule siloxane for reaction, the reaction conditions include: heating at 40° C. to 120° C. Further, the reaction time is 3 h to 6 h.

[0083] In the present application, the reaction mechanism for preparing the polyurethane composition can be summarized as follows: polysiloxane, a first polyol and an isocyanate compound are mixed to carry out a prepolymerization reaction to obtain a prepolymer, and then a second polyol and a polyhydroxy tertiary amine are added to the prepolymer to mix, and a chain extension reaction is carried out to obtain a chain extension product, and then the chain extension product is end-capped with a small molecule siloxane to obtain an end-capped product, and the end-capped product is then cured to obtain.

[0084] In some embodiments, polysiloxane such as As indicated, the first polyol is As indicated, isocyanate compounds such as As indicated, the second polyol is As indicated, polyhydroxy tertiary amines such as As indicated, the products of the chain extension reaction, such as prepolymers, As indicated, small molecule siloxanes such as As indicated, the end-capped product is As indicated, the polyurethane composition is indicated;

[0085] in,

[0086] n is an integer greater than 0 and the molecular weight of the polysiloxane is 200Da to 20000Da, and m is selected from 1, 2, 3 or 4;

[0087] XH is an active hydrogen functional group, further, X is O, S, N or an ester group;

[0088] YH is an active hydrogen functional group, further, Y is O, S, N or an ester group;

[0089] R1 is an alkyl group having 1 to 4 carbon atoms, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, etc.;

[0090] R2 is cyano or

[0091] R3 is selected from Further, the preparation mechanism of the polyurethane composition is shown below:

[0092]

[0093]

[0094] In the third aspect of the present application, a use of a polyurethane composition in preparing a medical material for promoting tissue repair is provided. Preferably, the polyurethane composition is provided in the first aspect of the present application, or is prepared according to the preparation method in the second aspect of the present application.

[0095] In some embodiments, the polyurethane composition can be used to prepare a medical adhesive, which is non-toxic, harmless, has good biocompatibility, has strong adhesion to human tissue in a wet state, and is suitable for tissue wound closure to inhibit scar formation.

[0096] Biomedical materials need to have good tissue compatibility. The polyurethane composition of the present application has good compatibility with a variety of human tissues, and can be applied to a variety of soft / hard tissues such as skin, subcutaneous tissue, internal organs, bones and teeth.

[0097] The following are some specific embodiments.

[0098] For experimental parameters not specified in the following specific examples, reference is made to the instructions given in this application document, and reference may also be made to the experimental manuals in the art or other experimental methods known in the art, or to the experimental conditions recommended by the manufacturer. The raw materials and reagents involved in the following specific examples can be obtained commercially, or can be prepared by those skilled in the art according to known means.

[0099] The polysiloxanes in the following embodiments can be purchased from manufacturers such as Sinopharm Chemical Reagent Co., Ltd., Wuhan Kemeiwo Chemical Co., Ltd., and Shanghai Myrrel Chemical Technology Co., Ltd.; the first polyol can be purchased from Beijing Thompson Biotechnology Co., Ltd., Sinopharm Chemical Reagent Co., Ltd., Shanghai McLean Biochemical Technology Co., Ltd., Shanghai Aladdin Biochemical Technology Co., Ltd., and Nanjing Guochen Chemical Co., Ltd.; isocyanate compounds can be purchased from Wuhan Kamik Technology Co., Ltd., Shanghai Runjie Chemical Reagent Co., Ltd., and Shanghai Aladdin Biochemical Technology Co., Ltd.; catalysts can be purchased from Sinopharm Chemical Reagent Co., Ltd., Shanghai McLean Biochemical Technology Co., Ltd., and Shanghai Aladdin Biochemical Technology Co., Ltd.; the second polyol can be purchased from Shanghai Aladdin Biochemical Technology Co., Ltd., Sinopharm Chemical Reagent Co., Ltd. and other manufacturers; polyhydroxy tertiary amines can be purchased from Shanghai Aladdin Biochemical Technology Co., Ltd., Sinopharm Chemical Reagent Co., Ltd. and other manufacturers; small molecule siloxanes can be purchased from Shanghai McLean Biochemical Technology Co., Ltd., Beijing Bailingwei Technology Co., Ltd., Shanghai Titan Technology Co., Ltd., Shanghai Aladdin Biochemical Technology Co., Ltd. and other manufacturers.

[0100] Example 1

[0101] (1) Preparation

[0102] Weigh the corresponding weight portions of each raw material according to Table 1:

[0103] Table 1 Types, weight fractions and parameters of various raw materials used in Example 1

[0104]

[0105] In Table 1, the weight change before and after dehydration does not exceed 5% of the initial amount. Dehydration is to allow the reaction to proceed smoothly, and the weight loss can be ignored.

[0106] The specific dehydration method is as follows: add polysiloxane and the first polyol into the first reactor, fully stir and maintain the temperature at 110°C, evacuate to a vacuum degree of less than -0.09 MPa and dehydrate for 3 hours to obtain dehydrated amino PDMS (2000 Da) and PLG (800 Da).

[0107] Add the polyhydroxy tertiary amine and the second polyol into the second reactor, maintain the temperature at 110°C, evacuate to a vacuum degree of less than -0.09 MPa and dehydrate for 3 hours.

[0108] Add small molecule siloxane into the third reactor, maintain the temperature at 110°C, evacuate to a vacuum degree of less than -0.09 MPa and dehydrate for 3 hours.

[0109] (2) Prepolymerization

[0110] In the first reaction container, the polysiloxane and the first polyol after dehydration treatment were cooled to 70° C., and isocyanate compounds and catalysts were added under nitrogen protection and stirring conditions, and the reaction was carried out for 4 hours.

[0111] (3) Chain extension reaction

[0112] The dehydrated polyhydroxy tertiary amine and the second polyol were cooled to 70° C., added into the first reactor, and reacted for 4 hours under nitrogen protection.

[0113] (4) Capping reaction

[0114] The dehydrated small molecule siloxane was cooled to 70°C, added into the first reactor, reacted for 5 hours under nitrogen protection, and then free isocyanate compounds were removed by a thin film evaporator.

[0115] Example 2

[0116] (1) Preparation

[0117] Weigh the corresponding weight portions of each raw material according to Table 2:

[0118] Table 2 Types, weight fractions and parameters of raw materials used in Example 2

[0119]

[0120] In Table 2, the weight change before and after dehydration does not exceed 5% of the initial amount. Dehydration is to allow the reaction to proceed smoothly, and the weight loss can be ignored.

[0121] The specific dehydration method is as follows: add polysiloxane and the first polyol into the first reactor, fully stir and maintain the temperature at 110° C., evacuate to a vacuum degree of less than -0.09 MPa and dehydrate for 4 hours.

[0122] Add the polyhydroxy tertiary amine and the second polyol into the second reactor, maintain the temperature at 110°C, evacuate to a vacuum degree of less than -0.09 MPa and dehydrate for 3 hours.

[0123] Add small molecule siloxane into the third reactor, maintain the temperature at 110°C, evacuate to a vacuum degree of less than -0.09 MPa and dehydrate for 3 hours.

[0124] (2) Prepolymerization

[0125] In the first reaction container, the polysiloxane and the first polyol after dehydration treatment were cooled to 60° C., and isocyanate compounds and catalysts were added under nitrogen protection and stirring conditions, and the reaction was carried out for 6 hours.

[0126] (3) Chain extension reaction

[0127] The dehydrated polyhydroxy tertiary amine and the second polyol were cooled to 70° C., added into the first reactor, and reacted for 5 hours under nitrogen protection.

[0128] (4) Capping reaction

[0129] The dehydrated small molecule siloxane was cooled to 60°C, added into the first reactor, reacted for 3 hours under nitrogen protection, and then free isocyanate compounds were removed by a thin film evaporator.

[0130] Example 3

[0131] (1) Preparation

[0132] Weigh the corresponding weight portions of each raw material according to Table 3:

[0133] Table 3 Types, weight fractions and parameters of raw materials used in Example 3

[0134]

[0135] In Table 3, the weight change before and after dehydration does not exceed 5% of the initial amount. Dehydration is to allow the reaction to proceed smoothly, and the weight loss can be ignored.

[0136] The specific dehydration method is as follows: add polysiloxane and the first polyol into the first reactor, fully stir and maintain the temperature at 110° C., evacuate to a vacuum degree of less than -0.09 MPa and dehydrate for 3 hours.

[0137] Add the polyhydroxy tertiary amine and the second polyol into the second reactor, maintain the temperature at 120°C, evacuate to a vacuum degree of less than -0.09 MPa and dehydrate for 2 hours.

[0138] Add small molecule siloxane into the third reactor, maintain the temperature at 110°C, evacuate to a vacuum degree of less than -0.09 MPa and dehydrate for 3 hours.

[0139] (2) Prepolymerization

[0140] In the first reaction container, the polysiloxane and the first polyol after dehydration treatment were cooled to 70° C., and isocyanate compounds and catalysts were added under nitrogen protection and stirring conditions, and the reaction was carried out for 8 hours.

[0141] (3) Chain extension reaction

[0142] The dehydrated polyhydroxy tertiary amine and the second polyol were cooled to 70° C., added into the first reactor, and reacted for 5 hours under nitrogen protection.

[0143] (4) Capping reaction

[0144] The dehydrated small molecule siloxane was cooled to 60°C, added into the first reactor, reacted for 4 hours under nitrogen protection, and then free isocyanate compounds were removed by a thin film evaporator.

[0145] Comparative Example 1

[0146] (1) Preparation (without adding small molecule siloxane)

[0147] Weigh the corresponding weight portions of each raw material according to Table 4:

[0148] Table 4 Types, weight fractions and parameters of raw materials used in Comparative Example 2

[0149]

[0150] In Table 4, the weight change before and after dehydration does not exceed 5% of the initial amount. Dehydration is to allow the reaction to proceed smoothly, and the weight loss can be ignored.

[0151] The specific dehydration method is as follows: add polysiloxane and the first polyol into the first reactor, fully stir and maintain the temperature at 110° C., evacuate to a vacuum degree of less than -0.09 MPa and dehydrate for 4 hours.

[0152] Add the polyhydroxy tertiary amine and the second polyol into the second reactor, maintain the temperature at 110°C, evacuate to a vacuum degree of less than -0.09 MPa and dehydrate for 3 hours.

[0153] (2) Prepolymerization

[0154] In the first reaction container, the polysiloxane and the first polyol after dehydration treatment were cooled to 60° C., and isocyanate compounds and catalysts were added under nitrogen protection and stirring conditions, and the reaction was carried out for 6 hours.

[0155] (3) Chain extension reaction

[0156] The dehydrated polyhydroxy tertiary amine and the second polyol were cooled to 70°C, added into the first reactor, and reacted for 5 hours under nitrogen protection. The free isocyanate compounds were then removed by a thin film evaporator.

[0157] Comparative Example 2

[0158] (1) Preparation (without adding the second polyol and small molecule siloxane)

[0159] Weigh the corresponding weight portions of each raw material according to Table 5:

[0160] Table 5 Types, weight fractions and parameters of raw materials used in Comparative Example 2

[0161]

[0162] In Table 5, the weight change before and after dehydration does not exceed 5% of the initial amount. Dehydration is to ensure the smooth progress of the reaction, and the weight loss can be ignored. The specific dehydration method is as follows: add polysiloxane and the first polyol into the first reactor, stir well and maintain the temperature at 110°C, evacuate to a vacuum degree of less than -0.09MPa and dehydrate for 4h.

[0163] Add polyhydroxy tertiary amine into the second reactor, maintain the temperature at 110°C, evacuate to a vacuum degree of less than -0.09 MPa and dehydrate for 3 hours.

[0164] (2) Prepolymerization

[0165] In the first reaction container, the polysiloxane and the first polyol after dehydration treatment were cooled to 70° C., and isocyanate compounds and catalysts were added under nitrogen protection and stirring conditions, and the reaction was carried out for 5 hours.

[0166] (3) Chain extension reaction

[0167] The dehydrated polyhydroxy tertiary amine was cooled to 60°C and added into the first reactor to react for 4 hours under nitrogen protection. The free isocyanate compounds were then removed by a thin film evaporator.

[0168] Comparative Example 3

[0169] (1) Preparation (without adding polyhydroxy tertiary amine and small molecule siloxane)

[0170] Weigh the corresponding weight portions of each raw material according to Table 6:

[0171] Table 6 Types, weight fractions and parameters of raw materials used in Comparative Example 3

[0172]

[0173] In Table 6, the weight change before and after dehydration does not exceed 5% of the initial amount. Dehydration is to allow the reaction to proceed smoothly, and the weight loss can be ignored.

[0174] The specific dehydration method is as follows: add polysiloxane and the first polyol into the first reactor, fully stir and maintain the temperature at 110° C., evacuate to a vacuum degree of less than -0.09 MPa and dehydrate for 5 hours.

[0175] Add polyhydroxy tertiary amine into the second reactor, maintain the temperature at 110°C, evacuate to a vacuum degree of less than -0.09 MPa and dehydrate for 3 hours.

[0176] (2) Prepolymerization

[0177] In the first reaction container, the polysiloxane and the first polyol after dehydration treatment were cooled to 80° C., and isocyanate compounds and catalysts were added under nitrogen protection and stirring conditions, and the reaction was carried out for 5 hours.

[0178] (3) Chain extension reaction

[0179] The second polyol after dehydration treatment was cooled to 80°C, added into the first reactor, and reacted for 4 hours under nitrogen protection. Then, the free isocyanate compounds were removed by thin film evaporator.

[0180] Performance Testing

[0181] The multi-crosslinked silicone-based polyurethane compositions prepared in Examples 1-3 and Comparative Examples 1-3 were subjected to various performance tests, including adhesive viscosity, initial curing time test, adhesive strength test, skin irritation index (PII) test, skin sensitization test, biodegradation test, and biological toxicity test. The specific test methods are as follows:

[0182] Viscosity test: Use NDJ-79 digital rotational viscometer to test the viscosity of the adhesive at 37°C.

[0183] Initial curing time test (non-sticky time): Apply the multi-cross-linked silicone-based polyurethane composition to the surface of wet pig skin. When the surface of the biofunctional single-component medical adhesive is not sticky when touched, it is the initial curing time of the multi-cross-linked silicone-based polyurethane composition adhesive.

[0184] Adhesion strength test: Take two pieces of pig skin with a size of 60mm×20mm×2mm, keep the surface of the pig skin moist, mark an area of ​​25mm×10mm on the surface of each piece of pig skin, evenly apply the multi-cross-linked silicone-based polyurethane composition on the marked position of the two pieces of pig skin, then stick the two pieces of pig skin together, leave them to cure in a humid state at room temperature for 60 minutes, and then use a tensile testing machine for testing.

[0185] Skin irritation index (PII) test: Conducted according to the method specified in GB / T16886.10-2000, requiring acute contact for 24 hours, and the index should not be greater than 0.5.

[0186] Skin sensitization test: Conducted according to the closed sensitization test method specified in GB / T16886.10-2000.

[0187] Biodegradation test: Weigh an appropriate amount of a multi-cross-linked silicone-based polyurethane composition sample into a round flat-bottomed polytetrafluoroethylene dish, use the fluidity of the colloid itself to make it evenly leveled, and solidify it in a room temperature and humid environment to form a film. After the film is formed, place it in a 60°C vacuum drying oven to dry. Weigh the film that has been dried to a constant weight (cut into 2cm×2cm), and then place it in a 1.5mg / mL PBS buffer solution. Maintain the test environment at a constant temperature of 37°C. After 7 weeks, take out the film, wash it with distilled water, and dry it in a vacuum drying oven for 48 hours, and then calculate the weight change. Calculate the in vitro biodegradation rate using the following formula:

[0188] Degradation rate (%) = (W o -W d ) / W o ×100%;

[0189] Among them, W o and W d Represent the dry weight of samples before and after degradation, respectively.

[0190] Biological toxicity test: 0.2g of the cured adhesive was implanted into the subcutaneous tissue of rats for 4 weeks, and the changes in the skin appearance (color, temperature, exudation) of the material were observed. After 4 weeks, the subcutaneous tissue structure and the amount of inflammatory cells were evaluated by eosin-hematoxylin (HE) staining of paraffin sections of the animal, and the biocompatibility and cytotoxicity of the material were quantitatively analyzed. Biological toxicity test was compared with commercially available α-cyanoacrylate adhesives. The grading standard of inflammatory cells is shown in Table 7.

[0191] Table 7. Inflammatory cell grading criteria

[0192] level Inflammatory cell count + No or only a few lymphocytes were seen around the material ++ A small number of lymphocytes can be seen around the material +++ A small amount of neutrophils, lymphocyte infiltration, and giant cell reaction can be seen around the material ++++ Inflammatory reaction mainly characterized by neutrophil infiltration and phagocytes can be seen around the material.

[0193] The viscosity, initial curing time and bonding strength of the silicone-based polyurethane composition adhesives prepared in Examples 1 to 3 and Comparative Examples 1 to 3 are shown in Table 8 below.

[0194] Table 8. Viscosity, initial curing time, and adhesive strength of polyurethane compositions

[0195] Viscosity (mPa.s) Initial curing time Adhesion strength (kPa) Example 1 5600 3min10s 308 Example 2 5800 4min5s 282 Example 3 6200 3min30s 295 Comparative Example 1 7100 7min30s 126 Comparative Example 2 6800 6min40s 153 Comparative Example 3 7600 8min50s 113

[0196] Skin irritation index (PII) test results: The skin irritation index of the silicone-based polyurethane compositions prepared in Examples 1 to 3 and Comparative Examples 1 to 3 was all 0.

[0197] Skin allergy test results: The silicone-based polyurethane compositions prepared in Examples 1 to 3 and Comparative Examples 1 to 3 had no skin allergy.

[0198] The biodegradation test and biotoxicity test results of the silicone-based polyurethane compositions prepared in Examples 1 to 3 and Comparative Examples 1 to 3 are shown in Table 9 below.

[0199] Table 9. Biodegradation and biotoxicity of polyurethane compositions

[0200]

[0201] It can be seen from the above test results that Examples 1 to 3 can prepare multi-crosslinked silicone-based polyurethane compositions with suitable viscosity, moderate curing speed, greater adhesive strength, faster degradation speed and lower toxicity.

[0202] Compared with commercially available α-cyanoacrylate adhesives, the multi-crosslinked silicone-based polyurethane compositions prepared in Examples 1 to 3 only cause a relatively mild inflammatory response to the organism, have good biocompatibility, and low biological toxicity.

[0203] Compared with Comparative Examples 1, 2 and 3, although the glue viscosity of the multi-cross-linked silicone-based polyurethane composition of Example 1 is relatively small and the prepared polyurethane composition has stronger adhesive strength, it can be seen that the presence of the second small molecule siloxane can improve the cross-linking density of the multi-cross-linked silicone-based polyurethane, enhance the adhesive strength and mechanical strength of the multi-cross-linked silicone-based polyurethane composition, and the inflammatory response and biological toxicity of Comparative Example 2 are relatively large.

[0204] Compared with Comparative Example 1, Example 2 has the same formula, but Example 1 has a faster degradation rate and more significant mechanical properties. It can be seen that the preparation method of Example 1 that first introduces small molecule siloxane end-capping is beneficial for preparing a multi-cross-linked silicone-based polyurethane composition with a faster degradation rate and better mechanical properties.

[0205] All documents mentioned in this application are cited as references in this application, just as each document is cited as reference separately. Unless they conflict with the application purpose and / or technical solution of this application, the cited documents involved in this application are cited with all contents and all purposes. When the cited documents are involved in this application, the definitions of relevant technical features, terms, nouns, phrases, etc. in the cited documents are also cited. When the cited documents are involved in this application, the examples and preferred methods of the cited relevant technical features can also be incorporated into this application as references, but are limited to the implementation of this application. It should be understood that when the cited content conflicts with the description in this application, the present application shall prevail or be modified adaptively according to the description of this application.

[0206] The technical features of the above-mentioned implementation modes and examples can be combined in any appropriate manner. To make the description concise, not all possible combinations of the technical features in the above-mentioned implementation modes and examples are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0207] The above-described embodiments only express several implementation methods of the present application, but they cannot be understood as limiting the scope of the patent application. It should be pointed out that, for those of ordinary skill in the art, without departing from the concept of the present application, several variations and improvements can also be made, which all belong to the protection scope of the present application. In addition, it should be understood that after reading the above-mentioned teaching content of the present application, those skilled in the art can make various changes or modifications to the present application, and the equivalent forms obtained also fall within the protection scope of the present application. It should also be understood that the technical solutions obtained by those skilled in the art on the basis of the technical solutions provided in the present application through logical analysis, reasoning or limited experiments are all within the protection scope of the claims attached to the present application. Therefore, the protection scope of the patent of the present application shall be based on the attached claims, and the description can be used to interpret the content of the claims.

Claims

1. A polyurethane composition, characterized in that The invention comprises the following raw material components in parts by weight: 50 to 120 parts of polysiloxane, 20 to 60 parts of a first polyol, 100 to 200 parts of an isocyanate compound, 0 to 0.5 parts of a catalyst, 5 to 15 parts of a second polyol, 0.5 to 8 parts of a polyhydroxy tertiary amine, and 10 to 40 parts of a small molecular siloxane; Wherein, the polysiloxane meets the following characteristics: (a1) the molecular weight is 200Da to 20000Da; (a2) the end is capped with an active hydrogen functional group; The first polyol is a polymer polyol, and the molecular weight of the polymer polyol is 600Da to 10000Da; The isocyanate compound meets the following characteristics: (b1) a molecular weight of 60Da to 800Da; (b2) an average functionality of 2 to 4; The second polyol is a small molecule polyol; The polyhydroxy tertiary amine meets the following characteristics: (c1) a molecular weight of 60Da to 500Da; (c2) an average functionality of 2 to 4; The small molecule siloxane meets the following characteristics: (d1) the molecular weight is 100Da to 1000Da; (d2) one of the end caps directly connected to silicon is an active hydrogen functional group, and the other three ends directly connected to silicon are the same alkoxy groups; the small molecule siloxane includes mercapto-terminated trimethoxysilane, mercapto-terminated triethoxysilane, hydroxyl-terminated trimethoxysilane, hydroxyl-terminated triethoxysilane, amino-terminated trimethoxysilane, amino-terminated triethoxysilane or a combination thereof; The polyurethane composition does not include a solvent; The preparation method of the polyurethane composition comprises the following steps: The polysiloxane, the first polyol and the isocyanate compound are mixed, the catalyst is added, and a prepolymerization reaction is carried out under a protective gas atmosphere to obtain a prepolymer; Mixing the prepolymer, the second polyol and the polyhydroxy tertiary amine, and performing a chain extension reaction under a protective gas atmosphere; and The small molecule siloxane is added to the product of the chain extension reaction to carry out reaction.

2. The polyurethane composition according to claim 1, characterized in that The active hydrogen functional group includes a hydroxyl group, a thiol group, an amino group, a carboxyl group or a combination thereof.

3. The polyurethane composition according to claim 1, characterized in that The small molecule polyol is selected from: glycerol, ethylene glycol, 1,4-butanediol, 1,6-hexanediol, 1,8-octanediol or a combination thereof; The polymer polyol is selected from: polyether polyol, polyester polyol or a combination thereof.

4. The polyurethane composition according to any one of claims 1 to 3, characterized in that The polyvalent hydroxy tertiary amine includes triethanolamine, triisopropanolamine, N-methyldiethanolamine, N-ethyldiethanolamine, N-n-propyldiethanolamine, tert-butyldiethanolamine or a combination thereof.

5. The polyurethane composition according to any one of claims 1 to 3, characterized in that The isocyanate compound includes hexamethylene diisocyanate, 4,4-bis(isocyanate cyclohexyl)methane, 2,2,4-trimethylhexane diisocyanate, L-lysine diisocyanate, 2,6-diisocyanate methylhexanoate, isophorone diisocyanate or a combination thereof.

6. The polyurethane composition according to any one of claims 1 to 3, characterized in that The catalyst includes an organic tin catalyst, an organic bismuth catalyst, an amine catalyst or a combination thereof.

7. The polyurethane composition according to claim 1, characterized in that It has one or more of the following technical features: (e1) The prepolymerization reaction conditions include: heating at 50°C to 90°C; (e2) The conditions of the chain extension reaction include: heating at 50° C. to 90° C.; (e3) In the step of adding small molecule siloxane to react, the reaction conditions include: heating at 40°C to 120°C.

8. Use of the polyurethane composition according to any one of claims 1 to 7 in the preparation of medical materials for promoting tissue repair.

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