Biological tissue with bending resistance as well as preparation method and application of biological tissue

Abstract

The invention provides a biological tissue with bending resistance as well as a preparation method and application thereof, and belongs to the technical field of biological tissues, the biological tissue is prepared by the following method: degreasing a cross-linked biological tissue to obtain a degreased biological tissue; reacting the degreased biological tissue with a solution containing a prepolymer, and carrying out anti-calcification and dehydration treatment to obtain the biological tissue with anti-bending performance, the prepolymer is formed by isocyanate and polyol, and the biological tissue uses the prepolymer, so that the reaction can be better controlled, and the situation that chain extension cannot be carried out due to rapid polymerization is avoided. The biological tissue contains more hydroxyl groups, the prepolymer can ensure that-NCO of the prepolymer is combined with the hydroxyl groups in the biological tissue, meanwhile, the prepolymer contains not less than three-NCO groups, and after the prepolymer reacts with the hydroxyl groups on the biological tissue, network cross-linking exceeding glutaraldehyde two-point linear cross-linking is formed, so that the toughness and the strength of the material can be better improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biological tissues, in particular to a biological tissue with anti-bending performance, a preparation method and application thereof. BACKGROUND

[0002] The current dry biological valve is the mainstream technical route for further improving the anti-calcification performance of the product. At the same time, the cleaning-free dry valve further shortens the preparation time of the operation, and also provides more packaging methods for the instrument. In order to further simplify the preparation time of the instrument during the operation, a feasible solution is to pre-assemble the instrument.

[0003] When the instrument is pre-assembled, the three valve leaves of the valve are in a bent state. The valve leaf material is in a folded state or even a pressed state during storage for a long time. The traditional animal-derived valve leaf material will form significant folds or indentations under this condition, causing damage to the tissue or abnormality of the valve leaf during opening and closing. SUMMARY

[0004] In view of the technical problems in the prior art, the present application provides a biological tissue with anti-bending performance, a preparation method and application thereof. The biological tissue with anti-bending performance is obtained by reacting a defatted biological tissue with a solution containing a prepolymer. The obtained biological tissue can avoid damage caused by folds or indentations.

[0005] The specific technical solutions of the present application are as follows: The present application provides the use of a prepolymer in the preparation of a biological tissue with anti-bending performance. The prepolymer is a prepolymer formed from isocyanate and polyol.

[0006] Preferably, for the use described above, the isocyanate is selected from one or more of toluene diisocyanate, diphenylmethane diisocyanate, hexamethylene diisocyanate and dicyclohexylmethane diisocyanate.

[0007] Preferably, for any of the uses described above, the polyol is selected from one or more of glycerol, pentaerythritol, sorbitol, mannitol and sucrose.

[0008] The present application provides a method for preparing a biological tissue with anti-bending performance, which comprises: defatting the cross-linked biological tissue to obtain a defatted biological tissue; reacting the defatted biological tissue with a solution containing a prepolymer, and performing anti-calcification and dehydration treatment to obtain a biological tissue with anti-bending performance; The prepolymer is a prepolymer formed from isocyanate and polyol.

[0009] Preferably, for the above-mentioned method, wherein the isocyanate is selected from one or more than two of toluene diisocyanate, diphenyl methane diisocyanate, hexamethylene diisocyanate and dicyclohexyl methane diisocyanate; and / or The polyol is selected from one or more than two of glycerol, pentaerythritol, sorbitol, mannitol and sucrose.

[0010] Preferably, for the above-mentioned method, the molar ratio of -NCO of the isocyanate and -OH in the polyol is 1-3:1, preferably 1.8-2.2:1.

[0011] Preferably, for the above-mentioned method, the reaction temperature in the step of preparing the prepolymer is 50-100°C; and / or The reaction time is 1-48h.

[0012] Preferably, for the above-mentioned method, the reaction temperature in the step of reacting the defatted biological tissue with the solution containing the prepolymer is 20-50°C, and / or The reaction time is 1-48h.

[0013] The application provides a biological tissue with anti-bending performance, which is prepared by the above-mentioned method.

[0014] The application provides the use of the biological tissue in preparing a biological valve.

[0015] Effects of the application The use of the prepolymer in the application can better control the reaction and avoid rapid polymerization leading to chain extension. The biological tissue contains a large number of hydroxyl groups, and the use of the prepolymer can ensure the combination of -NCO of the prepolymer and the hydroxyl groups on the biological tissue. Meanwhile, the prepolymer contains not less than three -NCO groups, and after reacting with the hydroxyl groups on the biological tissue, a network crosslinking structure with more than two linear crosslinking points of glutaraldehyde is formed. The three-dimensional network crosslinking structure can better improve the toughness and strength of the material compared with the linear crosslinking structure of glutaraldehyde.

[0016] The biological tissue described in the application has excellent crease recovery performance, i.e. excellent anti-bending performance. BRIEF DESCRIPTION OF DRAWINGS

[0017] Figure 1 is a flow chart for preparing a biological tissue with anti-bending performance.

[0018] Figure 2 is a schematic diagram of the crease recovery performance of the biological tissue obtained in the examples and comparative examples. DETAILED DESCRIPTION

[0019] The application will be described in detail below with reference to the embodiments described. Although specific embodiments of the application are shown, it is understood that the application can be implemented in various forms and should not be limited by the embodiments set forth herein. On the contrary, these embodiments are provided so that the application can be more thoroughly and completely understood, and so that the scope of the application can be fully conveyed to those skilled in the art.

[0020] It should be noted that some terms are used in the description and claims to refer to certain components. Those skilled in the art will understand that the same component can be referred to by different names. The description and claims of the present application do not distinguish components based on the difference in names, but rather on the difference in functions. As mentioned throughout the description and claims, "comprising" or "including" is an open term, which should be interpreted as "including but not limited to". The subsequent description is a preferred embodiment of implementing the application, but the description is for the purpose of the general principles of the description, and is not intended to limit the scope of the application. The scope of protection of the application is defined by the appended claims.

[0021] The application provides the use of a prepolymer in the preparation of a biological tissue with anti-bending performance, the prepolymer being a prepolymer formed by isocyanate and polyol.

[0022] The prepolymer is a prepolymer formed by isocyanate and polyol, which is used in biological tissue and can enhance the crosslinking of biological tissue. It can improve the elasticity of biological tissue while increasing the crosslinking degree of biological tissue, and can improve the anti-bending performance of biological tissue, so as to avoid damage to biological tissue caused by creases or indentations.

[0023] In the present application, the biological tissue is not limited, and it can be a conventional biological tissue in the art, for example, it can be a biological tissue of a mammal, for example, it can be a pericardium, a heart valve, a covering membrane, a pleura, a small intestinal submucosa, a dura mater, a spinal cord membrane, a ligament or skin, etc. The pericardium can be a pericardium of a mammal, for example, it can be a bovine pericardium, a porcine pericardium, etc.

[0024] In some embodiments, the isocyanate is selected from one or more of toluene diisocyanate, diphenylmethane diisocyanate, hexamethylene diisocyanate and dicyclohexylmethane diisocyanate. In some embodiments, the polyol is selected from one or more of glycerol, pentaerythritol, sorbitol, mannitol and sucrose.

[0025] The application provides a method for preparing a biological tissue with anti-bending performance, comprising: The crosslinked biological tissue is defatted to obtain a defatted biological tissue; The defatted biological tissue is reacted with a solution containing prepolymer, and then subjected to anti-calcification and dehydration treatment to obtain biological tissue with flexural strength. The prepolymer is a prepolymer formed from isocyanate and polyol.

[0026] In this application, no restrictions are placed on the degreasing method. Those skilled in the art can make conventional choices based on actual needs, such as placing the cross-linked biological tissue into a degreasing agent to obtain the degreased biological tissue.

[0027] In this application, no restrictions are placed on the degreasing agent. Those skilled in the art can use conventional degreasing agents for degreasing, such as one or more of acetone, ether, ethanol, isopropanol and limonene.

[0028] In this application, the degreasing temperature and degreasing time can be those conventionally used in the art, as long as they meet the requirements of this application.

[0029] For example, the degreasing temperature can be 1-7℃, and the degreasing time can be 1-5 days.

[0030] For example, the defatting temperature can be 1℃, 2℃, 3℃, 4℃, 5℃, 6℃, 7℃, etc., and the defatting time can be 1 day, 2 days, 3 days, 4 days, 5 days, etc.

[0031] In this application, cross-linked biological tissues can be degreased once or multiple times, as needed, and the same or different degreasing agents can be used each time.

[0032] This application removes fat from cross-linked biological tissues, thereby freeing up the space occupied by fat in the biological tissues.

[0033] Reacting the defatted biological tissue with a solution containing a prepolymer refers to polymerizing the hydroxyl groups of the defatted biological tissue with the prepolymer in the solution.

[0034] In some embodiments, the isocyanate is selected from one or more of toluene diisocyanate, diphenylmethane diisocyanate, hexamethylene diisocyanate, and dicyclohexylmethane diisocyanate; and / or the polyol is selected from one or more of glycerol, pentaerythritol, sorbitol, mannitol, and sucrose.

[0035] In this application, a solution containing the prepolymer refers to a solution obtained by dissolving the prepolymer in a solvent. No restrictions are placed on the solvent used in this application; those skilled in the art can choose conventionally according to actual needs, as long as the requirements of this application are met. For example, the solvent can be butyl acetate, propylene glycol methyl ether acetate, ethylene glycol butyl ether acetate, etc. Similarly, no restrictions are placed on the amount of solvent used in this application, as long as the prepolymer is dissolved in the solvent.

[0036] In some embodiments, the molar ratio of -NCO in the isocyanate to -OH in the polyol is 1-3:1, preferably 1.8-2.2:1.

[0037] For example, the molar ratio (n) of -NCO in the isocyanate and -OH in the polyol. 异氰酸酯的-NCO :n 多元醇中的-OH The ratios can be 1.0:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, 2.0:1, 2.1:1, 2.2:1, 2.3:1, 2.4:1, 2.5:1, 2.6:1, 2.7:1, 2.8:1, 2.9:1, 3.0:1, etc.

[0038] In some embodiments, the reaction temperature is 50-100°C during the prepolymer preparation step; and / or The reaction time is 1-48 hours; In the step of reacting the defatted biological tissue with a solution containing the prepolymer, the reaction temperature is 20-50°C, and / or The reaction time is 1-48 hours.

[0039] For example, in the step of preparing the prepolymer, the reaction temperature can be 50℃, 55℃, 60℃, 65℃, 70℃, 75℃, 80℃, 85℃, 90℃, 98℃, 100℃, etc.; the reaction time can be 1h, 5h, 10h, 15h, 20h, 25h, 30h, 35h, 40h, 45h, 48h, etc.

[0040] In the step of reacting the defatted biological tissue with the solution containing the prepolymer, the reaction temperature can be 20℃, 21℃, 22℃, 23℃, 24℃, 25℃, 26℃, 27℃, 28℃, 29℃, 30℃, 31℃, 32℃, 33℃, 34℃, 35℃, 36℃, 37℃, 38℃, 39℃, 40℃, 41℃, 42℃, 43℃, 44℃, 45℃, 46℃, 47℃, 48℃, 49℃, 50℃, etc.; the reaction time can be 1h, 5h, 10h, 15h, 20h, 25h, 30h, 35h, 40h, 45h, 48h, etc.

[0041] For example, the process for preparing biological tissues with bending resistance is as follows: Figure 1 As shown.

[0042] This application provides a biological tissue with bending resistance, which is prepared by the method described above.

[0043] The biological tissue described in this application uses a prepolymer to cross-link with the biological tissue, which can improve the toughness and strength of the biological tissue and has excellent bending resistance, thus avoiding damage caused by creases or indentations.

[0044] This application provides the use of the biological tissue described above in the preparation of biological valves.

[0045] Example This application provides a general and / or specific description of the materials and test methods used in the experiments. In the following examples, unless otherwise specified, % represents wt%, i.e., weight percentage. Reagents or instruments used, unless otherwise specified, are all commercially available conventional reagent products.

[0046] Example 1 based on Figure 1 The flowchart in the image shows the preparation of calf heart with flexural strength: 1. Cross-linking: Place one piece of veal heart into 1000ml of 0.625 wt% glutaraldehyde solution and cross-link at 35℃ for 48h to obtain fixed veal heart.

[0047] 2. Degreasing: Place the fixed veal heart into 100ml of a 20% ethanol: 80% ether mixture as a degreasing agent and soak at 4℃ for 1.5 days to obtain degreased veal heart.

[0048] 3. Polymerization reaction: The defatted veal heart was placed in 100g of a solution containing the prepolymer, and the hydroxyl groups in the prepolymer and the defatted veal heart heart were subjected to a polymerization reaction at 30°C for 24h. The pH of the reaction system was adjusted to neutral. The solution containing the prepolymer was prepared as follows: Under stirring conditions, 200g of 3% glycerol-butyl acetate solution was slowly added to 800g of 4.1% hexamethylene diisocyanate-butyl acetate solution, the pH was adjusted to neutral, and the reaction was carried out at 70℃ for 2h to obtain a solution of low molecular weight prepolymer with multiple -NCO groups at the end.

[0049] 4. Anti-calcification: The pericardium obtained after polymerization reaction is subjected to calcification treatment according to the method disclosed in Chinese Patent CN 113080187 B to obtain anti-calcification pericardium.

[0050] 5. Dehydration: Soak the anti-calcification bovine pericardium in glycerol at room temperature for 2 hours. Then, lower the temperature of the soaked bovine pericardium from room temperature to -20°C at a rate of 1°C / min, and then lower it from -20°C to -60°C at a rate of 90°C / min. At -60°C, apply a vacuum to 1 Pa and dry for 5 hours. Then, raise the temperature from -60°C to -30°C at a rate of 1°C / min and dry for 1 hour. Finally, adjust the vacuum to 50 Pa and raise the temperature from -20°C to 25°C at a rate of 1°C / min and dry for 1 hour to obtain the dehydrated bovine pericardium.

[0051] 6. Packaging and sterilization: The dehydrated veal heart capsules are packaged and sterilized to obtain veal heart capsules with flexural strength.

[0052] Example 2 The difference between Example 2 and Example 1 is that the molar ratio of -NCO to -OH in the prepolymer preparation process is 3, resulting in a calf heart with flexural strength.

[0053] Example 3 The difference between Example 3 and Example 1 is that the molar ratio of -NCO to -OH in the prepolymer preparation process is 5, resulting in a calf heart with flexural strength.

[0054] Example 4 The difference between Example 4 and Example 1 is that the molar ratio of -NCO to -OH in the prepolymer preparation process is 0.5, resulting in a calf heart with flexural strength.

[0055] Example 5 The difference between Example 5 and Example 1 is that the isocyanate used is toluene diisocyanate, thereby obtaining a calf heart with flexural strength.

[0056] Example 6 The difference between Example 6 and Example 1 is that the polyol used is mannitol, thus obtaining a calf heart with bending resistance.

[0057] Comparative Example 1 The difference between Comparative Example 1 and Example 1 is that glutaraldehyde was used to crosslink and fix defatted bovine pericardium.

[0058] Experimental Example Elastic recovery rate test: The elastic recovery rate of the calf heart obtained from the examples and comparative examples was determined according to the standard test method of ASTM D638 for tensile properties of plastics. The results are shown in Table 1.

[0059] Tensile strength determination: The tensile strength of various bovine pericardiums obtained from the examples and comparative examples was determined according to the method disclosed in QBT2710-2018, and the results are shown in Table 1.

[0060] Table 1

[0061] Crease recovery performance evaluation: The crease recovery performance of the biological tissues obtained in Example 1 and Comparative Example 1 was evaluated according to ISO 9867:2022 Textiles—Assessment of wrinkle recovery in fabrics—Appearance method. Figure 2 As shown, where Figure 2 The left-hand diagram is a schematic diagram of the pericardium obtained in Example 1. Figure 2 The diagram on the right is a schematic diagram of the pericardium obtained in Scale 1.

[0062] from Figure 2 It can be seen that the pericarp obtained in Example 1 has superior bending resistance compared to the pericarp obtained in Comparative Example 1.

[0063] The above description is merely a preferred embodiment of this application and is not intended to limit the application in any other way. Any person skilled in the art may make changes or modifications to the disclosed technical content to create equivalent embodiments. However, any simple modifications, equivalent changes, and modifications made to the above embodiments based on the technical essence of this application without departing from the scope of the technical solution of this application shall still fall within the protection scope of this application.

Claims

1. Use of a prepolymer in the preparation of a biological tissue having anti-kinking property, the prepolymer being a prepolymer formed from an isocyanate and a polyol; the biological tissue being a pericardium; the isocyanate being selected from one or more than two of toluene diisocyanate, diphenylmethane diisocyanate, hexamethylene diisocyanate and dicyclohexylmethane diisocyanate; and / or the polyol being selected from one or more than two of glycerol, pentaerythritol, sorbitol, mannitol and sucrose; and / or the prepolymer containing not less than three -NCO groups.

2. A method for preparing a biological tissue having anti-kinking property, comprising: crosslinking a biological tissue to obtain a crosslinked biological tissue; defatting the crosslinked biological tissue to obtain a defatted biological tissue; reacting the defatted biological tissue with a solution containing a prepolymer, and performing anti-calcification and dehydration treatment to obtain a biological tissue having anti-kinking property; the prepolymer being a prepolymer formed from an isocyanate and a polyol; the biological tissue being a pericardium; the isocyanate being selected from one or more than two of toluene diisocyanate, diphenylmethane diisocyanate, hexamethylene diisocyanate and dicyclohexylmethane diisocyanate; and / or the polyol being selected from one or more than two of glycerol, pentaerythritol, sorbitol, mannitol and sucrose; and / or the prepolymer containing not less than three -NCO groups.

3. The method of claim 2, wherein the molar ratio of -NCO of the isocyanate to -OH of the polyol is 1-3:

1.

4. The method of any one of claims 2-3, wherein in the step of preparing the prepolymer, the reaction temperature is 50-100°C; and / or the reaction time is 1-48 h.

5. The method of any one of claims 2-3, wherein in the step of reacting the defatted biological tissue with the solution containing the prepolymer, the reaction temperature is 20-50°C, and / or the reaction time is 1-48 h.

6. A biological tissue having anti-kinking property, prepared by the method of any one of claims 2-5.

7. Use of the biological tissue of claim 6 in the preparation of a biological valve.

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