Method for producing an elastomeric material, impermeable vascular prosthesis and method for producing the same

Abstract

The application provides a preparation method of an elastomer material, a leakage-proof artificial blood vessel and a preparation method thereof, and belongs to the field of biomedical materials. Polyethylene glycol, hexamethylene diisocyanate and dibutyl tin dilaurate are dissolved in a mixed solution of a first solvent and tetrahydrofuran, a precursor solution is obtained after oil bath reaction at 50-80 DEG C for 3-24 hours, then a chain extender chitooligosaccharide is added for continuous reaction, and a polyurethane elastomer solution is obtained. The first solvent is one of N'N-dimethylacetamide and DMF. The application selects polyethylene glycol with good biocompatibility and degradability as a soft segment raw material, and selects chitooligosaccharide with a molecular weight of 1000-2500 as a chain extender, so that the prepared elastomer material has good in-vivo and in-vitro biocompatibility and degradability. The prepared polyurethane elastomer solution is sprayed on an artificial blood vessel, and a leakage-proof artificial blood vessel can be prepared. The tensile strength of the prepared leakage-proof artificial blood vessel is greater than or equal to 19 MPa, and the tear resistance can reach 162 kJ m ‑2 .

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical materials, and in particular to a preparation method of an elastomeric material, a leakage-proof artificial blood vessel and a preparation method thereof. Background Art

[0002] Currently, commercially available polymer-based artificial blood vessels primarily include polyester, silk, and polytetrafluoroethylene (PTFE) artificial blood vessels. These products are primarily formed through weaving, which primarily involves knitting, braiding, and weaving. Specifically, after being woven into a tubular fabric, post-processing produces a spiral-shaped artificial blood vessel that can bend freely without collapsing. However, since fibers are used in the weaving process, blood leakage between fibers is inevitable. Therefore, selecting the right material to seal the gaps between the artificial blood vessels is crucial for their stable operation.

[0003] Currently, to address leakage in artificial vascular materials, the primary approach to creating leak-proof coatings is to select or prepare biocompatible precursor materials, such as polyhydroxyalkanoates and collagen, from the raw materials. These materials are then dissolved and extracted, and then adhered to the artificial vascular graft. However, these materials are often brittle, tear-resistant, and prone to leakage. This inevitably leads to the material being easily torn and damaged during the grafting procedure, making the long-term use of the graft difficult.

[0004] Currently, a common approach is to increase the flexibility of the coating, such as collagen coating, by soaking it in saline before use. However, its tear resistance remains problematic. Once defects appear in the coating material, cracks quickly develop, rendering the material useless and failing to meet the anti-leakage requirements of artificial blood vessels. Furthermore, currently commercially available coatings lack the tear resistance required for suturing.

[0005] Although coating with a biocompatible material can alleviate the leakage problem of artificial blood vessels, insufficient strength, flexibility, tear resistance, leakage prevention, and biological cell adhesion and growth during use often result in less than ideal performance of these leak-proof artificial blood vessels during long-term use. Summary of the Invention

[0006] In view of the technical problems existing in the background technology, the present application provides a method for preparing an elastomeric material, a leakage-proof artificial blood vessel and a preparation method thereof, aiming to solve the problem of insufficient tear resistance of existing artificial blood vessels.

[0007] In a first aspect, an embodiment of the present application provides a method for preparing an elastomeric material, comprising the following steps:

[0008] S1, dissolving polyethylene glycol, hexamethylene diisocyanate, and dibutyltin dilaurate in a mixture of a first solvent and tetrahydrofuran, and reacting in an oil bath at 50-80° C. for 3-24 hours to obtain a precursor solution; the first solvent is N'N-dimethylacetamide or DMF;

[0009] S2, adding the chain extender chitosan oligosaccharide dissolved in N'N-dimethylacetamide to the precursor solution obtained in step S1 and continuing the reaction for 4-24 hours to obtain a polyurethane elastomer solution.

[0010] In some embodiments, in step S1, the molar ratio of polyethylene glycol to hexamethylene diisocyanate is 1:(2-2.4).

[0011] In some embodiments, the amount of chitosan oligosaccharide is 1%-8% by weight of polyethylene glycol.

[0012] In some embodiments, the amount of dibutyltin dilaurate is 1%-2% by mass of the polyethylene glycol.

[0013] In some embodiments, the molecular weight of the chitosan oligosaccharide is 1000-2500.

[0014] In some embodiments, in step S2, the reaction temperature is 20-50°C.

[0015] In some embodiments, in the mixture of the first solvent and tetrahydrofuran, the volume ratio of the first solvent to tetrahydrofuran is (4-6): (6-4).

[0016] In a second aspect, an embodiment of the present application provides a method for preparing a leakage-proof artificial blood vessel, using a polyurethane elastomer solution prepared by the aforementioned technical solution; the method comprises the following steps:

[0017] S3, placing the artificial blood vessel into the polyurethane elastomer solution for extraction; or spraying the polyurethane elastomer solution onto the artificial blood vessel to obtain an artificial blood vessel containing polyurethane;

[0018] S4, drying the artificial blood vessel containing polyurethane obtained in step S3 for 4-24 hours, then immersing it in pure water to remove impurities, taking it out and drying it to obtain a leakage-proof artificial blood vessel.

[0019] In some embodiments, the artificial blood vessel is a polyester or PTFE woven artificial blood vessel.

[0020] In some embodiments, in step S4, the drying temperature is 25-80°C.

[0021] In a third aspect, an embodiment of the present application provides an anti-leakage artificial blood vessel, which is prepared by the aforementioned preparation method. The anti-leakage artificial blood vessel comprises an artificial blood vessel substrate and a polyurethane anti-leakage coating supported on the surface of the artificial blood vessel substrate; the thickness of the polyurethane anti-leakage coating is 0.1-0.5 mm; the tensile strength of the anti-leakage artificial blood vessel is greater than or equal to 19 MPa, and the tear resistance can reach 162 kJ m -2 .

[0022] The beneficial effects of the present invention are:

[0023] (1) The preparation method of the elastomeric material of the present invention is divided into two steps, namely prepolymerization and chain extension. Specifically, the first step is to react polyethylene glycol with hexamethylene diisocyanate to obtain isocyanate-terminated polyethylene glycol, and the second step is to react the isocyanate group of the prepolymer with the amino group or hydroxyl group on the oligosaccharide to increase its molecular weight. The present invention uses polyethylene glycol with good biocompatibility and degradability as the soft segment raw material, and uses chitosan oligosaccharide with a molecular weight of 1000-2500 as the chain extender (which has good biocompatibility and degradability).

[0024] (2) The present invention uses a mixed solvent of THF and DMF or DMAC. Since oligosaccharides are difficult to dissolve in THF, a mixed solvent is required to ensure the normal progress of the second step chain extension reaction.

[0025] (3) The elastomeric material prepared by the present invention has good in vivo and in vitro biocompatibility and is also biodegradable.

[0026] (4) The method of the present invention is simple and convenient to operate, and the reaction conditions are mild. The obtained material has good mechanical properties, biocompatibility, and in vitro and in vivo degradation properties.

[0027] The above description is only an overview of the technical solution of the present application. In order to more clearly understand the technical means of the present application, it can be implemented in accordance with the contents of the specification. In order to make the above and other purposes, features and advantages of the present application more obvious and easy to understand, the specific implementation methods of the present application are listed below. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] To more clearly illustrate the technical solution of this application, the following is a brief introduction to the drawings used in this application. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be derived from these drawings without inventive effort.

[0029] Figure 1 This is a flow chart of the preparation method of the elastomeric material and the anti-leakage artificial blood vessel of the present application.

[0030] Figure 2Schematic diagram for the preparation of elastomeric materials.

[0031] Figure 3 These are the tensile curves, shapes, and tear performance diagrams of the elastomeric material prepared in Example 1 of the present application before and after soaking in saline; among them, a is a diagram showing the change in tensile properties of the elastomeric material before and after soaking in saline, b is a diagram showing the change in morphology of the elastomeric material before and after soaking in water, and c is a diagram showing the tensile properties and tear resistance of the elastomeric material after soaking in water.

[0032] Figure 4 The in vitro and in vivo compatibility data of the elastomeric material prepared in Example 1 and a blank sample are shown; wherein, a represents in vitro cell compatibility, b represents a cell fluorescence microscopy image, and c represents a subcutaneous tissue HE staining image.

[0033] Figure 5 Graphs showing the in vivo and in vitro degradation of the elastomeric material prepared in Example 1; wherein, a represents the in vivo degradation; and b represents the in vitro degradation.

[0034] Figure 6 These are the test results of hemolysis and coagulation properties of the extract of the elastomeric material prepared in Example 1. DETAILED DESCRIPTION

[0035] The following embodiments of the technical solution of the present application will be described in detail with reference to the accompanying drawings. The following embodiments are only used to more clearly illustrate the technical solution of the present application and are therefore only examples and are not intended to limit the scope of protection of the present application.

[0036] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this application belongs; the terms used herein are only for the purpose of describing specific embodiments and are not intended to limit this application; the terms "including" and "having" and any variations thereof in the specification and claims of this application and the above-mentioned figure descriptions are intended to cover non-exclusive inclusions.

[0037] In the description of the embodiments of this application, the technical terms "first" and "second" are used only to distinguish different objects and should not be understood to indicate or imply relative importance or implicitly specify the quantity, specific order, or primary and secondary relationship of the indicated technical features. In the description of the embodiments of this application, the meaning of "plurality" is more than two, unless otherwise clearly and specifically defined.

[0038] References herein to "embodiments" mean that a particular feature, structure, or characteristic described in connection with the embodiments may be included in at least one embodiment of the present application. The appearance of this phrase in various places in the specification does not necessarily refer to the same embodiment, nor does it constitute an independent or alternative embodiment that is mutually exclusive of other embodiments. It is understood, both explicitly and implicitly, by those skilled in the art that the embodiments described herein may be combined with other embodiments.

[0039] In the description of the embodiments of this application, the term "and / or" is simply a description of the association relationship between associated objects, indicating that three relationships can exist. For example, A and / or B can represent the following three situations: A exists alone, A and B exist simultaneously, and B exists alone. In addition, the character " / " in this document generally indicates that the associated objects are in an "or" relationship.

[0040] In the description of the embodiments of the present application, the term "multiple" refers to more than two (including two). Similarly, "multiple groups" refers to more than two groups (including two groups), and "multiple pieces" refers to more than two pieces (including two pieces).

[0041] For ordinary technicians in this field, the specific meanings of the above terms in the embodiments of this application can be understood according to specific circumstances.

[0042] Existing artificial blood vessels have insufficient anti-leakage performance and their tear resistance does not meet suturing requirements.

[0043] The present application provides a method for preparing an elastomeric material, comprising the following steps:

[0044] S1, dissolving polyethylene glycol, hexamethylene diisocyanate, and dibutyltin dilaurate in a mixture of a first solvent and tetrahydrofuran, and reacting in an oil bath at 50-80° C. for 3-24 hours to obtain a precursor solution;

[0045] The first solvent is N'N-dimethylacetamide or DMF. In the mixture of the first solvent and tetrahydrofuran, the volume ratio of the first solvent to tetrahydrofuran is (4-6): (6-4).

[0046] The molar ratio of the raw materials is: 1 part of polyethylene glycol, 2-2.4 parts of hexamethylene diisocyanate, and the amount of dibutyltin dilaurate is 1%-2% of the mass of polyethylene glycol.

[0047] S2, adding the chain extender chitosan oligosaccharide dissolved in N'N-dimethylacetamide to the precursor solution obtained in step S1 and continuing the reaction for 4-24 hours to obtain a polyurethane elastomer solution.

[0048] The molecular weight of chitosan oligosaccharide is 1000-2500. The amount of chitosan oligosaccharide used is 1%-8% of the mass of polyethylene glycol. The reaction temperature is 20-50°C.

[0049] The technical solution of the embodiment of the present application is divided into two steps: prepolymerization and chain extension. The first step is to react polyethylene glycol with hexamethylene diisocyanate to obtain isocyanate-terminated polyethylene glycol. The second step is to react the isocyanate group of the prepolymer with the amino group or hydroxyl group on the oligosaccharide to increase its molecular weight. Figure 2 shown.

[0050] This application uses biocompatible and degradable polyethylene glycol as the raw material for the soft segment, and the added chain extender is also chitosan oligosaccharide with good biocompatibility and degradability. The prepared elastomer has good in vitro and in vivo biocompatibility while also having degradable properties.

[0051] This application uses THF and DMF or DMAC to form a mixed solvent. Since oligosaccharides are difficult to dissolve in THF, a mixed solvent is required to ensure the normal progress of the second step chain extension reaction.

[0052] The present application also provides a method for preparing a leakage-proof artificial blood vessel, which comprises the following steps:

[0053] S3, leaching the artificial blood vessel in a polyurethane elastomer solution; or spraying the polyurethane elastomer solution onto the artificial blood vessel to obtain an artificial blood vessel containing polyurethane;

[0054] Among them, the artificial blood vessel is an artificial blood vessel woven with polyester and PTFE.

[0055] S4, drying the artificial blood vessel containing polyurethane obtained in step S3 for 4-24 hours, then immersing it in pure water to remove impurities, taking it out and drying it to obtain a leakage-proof artificial blood vessel.

[0056] The drying temperature is 25-80°C.

[0057] The present application also provides a leakage-proof artificial blood vessel, which is prepared using the above-mentioned preparation method. The leakage-proof artificial blood vessel includes an artificial blood vessel matrix and a polyurethane leakage-proof coating loaded on the surface of the artificial blood vessel matrix; the thickness of the polyurethane leakage-proof coating is 0.1-0.5mm.

[0058] The leak-proof artificial blood vessel has strong tear resistance and strength, and can reach a tensile strength of more than 19 MPa and a conductivity of about 162 kJ m -2 Tear resistance.

[0059] Some specific examples are listed below. It should be noted that the examples described below are exemplary and are only used to explain the present application, and should not be construed as limiting the present application. Where specific techniques or conditions are not specified in the examples, the techniques or conditions described in the literature in this area or the product specifications are used. Reagents or instruments used without manufacturer's indication are all commercially available conventional products.

[0060] The performance test method is as follows:

[0061] In vivo and in vitro biocompatibility experiments: CCK-8 method and Live / Dead fluorescence staining were used to detect the in vitro cell compatibility of the material.

[0062] The specific contents are as follows:

[0063] CCK-8 method to detect material cell compatibility:

[0064] Observe the growth status of L929 cells in the culture flask under a microscope. When the cell density reaches about 80%, pour out the old culture medium in the culture flask in a clean bench, add sterile PBS to rinse to remove the residual old culture medium, add 1 mL of trypsin containing EDTA and digest at room temperature for 2 minutes. Observe the cells under a microscope to see if they are completely digested. After confirmation, add 1 mL of fresh culture medium to terminate the digestion. Centrifuge the resulting cell suspension at 1200 rpm / min for 5 minutes. After centrifugation, discard the supernatant, add fresh culture medium to resuspend the cells, and count them using a cell counter. Dilute the cell concentration to 5×10 4 Cells were cultured in a 96-well plate at a concentration of 100 µL / well. The plates were incubated in a cell culture incubator for 24 hours. Culture medium containing the sample extract was then added to the wells of the experimental groups. A control group consisted of wells incubated with culture medium, while a blank group consisted of wells without cells. Three replicates were set up for each group. The 96-well plates were incubated in a cell culture incubator for 24 and 48 hours, respectively. After incubation, the old culture medium was discarded, and 100 µL of culture medium containing 10% CCK-8 was added to each well. After incubation in a dark incubator for 2 hours, the absorbance (OD) at 450 nm was measured using a microplate reader and the data recorded.

[0065] Cell survival rate = [(OD value of experimental group - OD value of blank group) / (OD value of control group - OD value of blank group)] × 100%

[0066] Live / Dead fluorescent staining to detect the cell compatibility of materials:

[0067] Observe the growth of L929 cells in the culture flask under a microscope. When the cell density reaches approximately 80%, pour out the old culture medium in the culture flask in a clean bench, rinse with sterile PBS to remove the remaining old culture medium, add 1 mL of trypsin containing EDTA and digest at room temperature for 2 minutes. Observe the cells under a microscope to see if they are completely digested. Once digestion is complete, add 1 mL of fresh culture medium to terminate digestion. Centrifuge the resulting cell suspension at 1200 rpm / min for 5 minutes. After centrifugation, discard the supernatant, resuspend the cells in fresh culture medium, and count them using a cell counter. Dilute the cells to a concentration of 5 × 10 4 Cells were cultured for 24 hours in a 96-well plate at a volume ratio of 100 μL / well. The plates were then incubated in a cell culture incubator for 24 hours. For the experimental groups, culture medium containing the sample extract was added to the cell wells and cultured for 24 and 48 hours, respectively. For the control group, culture medium was used for 24 and 48 hours, with three replicates per group. Following incubation, a reaction solution containing the AM / PI staining kit and culture medium at a 1:1000 volume ratio was added to the 96-well plate. The plates were then incubated in an incubator for 20 minutes and photographed using a fluorescence microscope.

[0068] The in vivo degradation performance test process is to place the elastomer in the subcutaneous tissue of the mouse back, and the in vitro degradation experiment is carried out in PBS buffer under the condition of lipase.

[0069] In vivo tissue compatibility testing involves implanting sterile samples subcutaneously on both sides of the mouse's back for a set period of time. The skin is then dissected and photographed. Surrounding tissue is then removed, embedded in paraffin, and stained with HE to determine if an inflammatory response is induced.

[0070] Mechanical testing: Tensile strength was tested using a universal testing machine at 30 mm / min. Tear resistance was tested using a pure shear method. For the pure shear test, the grip spacing was 5 mm, the sample was 25 mm long, and a 10 mm notch was made in the middle using a parallel blade. The maximum value was taken.

[0071] Leakage test: The artificial blood vessel integral water permeability tester is used to evaluate the water permeability (16 kPa) of artificial blood vessels in the application environment, referring to the method of "YY / T 0500-2021 Cardiovascular Implants Vascular Prostheses Tubular Vascular Grafts and Vascular Patches".

[0072] Example 1

[0073] See also Figure 1 As shown, this embodiment provides a method for preparing a leakage-proof artificial blood vessel, comprising the following steps:

[0074] S1. Accurately weigh 12 g of dried, dehydrated polyethylene glycol (0.006 mol, with a molecular weight of Mn = 2000), 0.12 g of dibutyltin dilaurate (0.000158 mol), and 2.01 g of hexamethylene diisocyanate (0.012 mol) and dissolve them in 200 ml of a mixture of tetrahydrofuran (THF) and N'N-dimethylacetamide. React in an oil bath at 60°C for 24 hours to obtain a precursor solution.

[0075] The dosage of each raw material is as follows: the molar ratio of polyethylene glycol to hexamethylene diisocyanate is 1:2, and the dosage of dibutyltin dilaurate is 1% of the mass of polyethylene glycol.

[0076] Wherein, in the mixed solution, the volume ratio of THF to N'N-dimethylacetamide is 1:1.

[0077] S2, dissolving 0.36 g of chitosan oligosaccharide (3% by mass of polyethylene glycol) in 20 ml of N'N-dimethylacetamide (DMAc) and injecting the solution into the above reaction vessel, and continuing the reaction at 40°C for 8 hours to obtain a polyurethane elastomer solution; the molecular weight of chitosan oligosaccharide is Mn=2200.

[0078] It should be noted that in order to subsequently test the mechanical properties of the polyurethane elastomer, the obtained polyurethane elastomer solution was dried at 70°C, and then the obtained polyurethane elastomer film was immersed in pure water to remove impurities and dry to obtain the final elastomer material for testing.

[0079] S3, extracting the polyester woven artificial blood vessel in the polyurethane elastomer solution obtained in step S2 to obtain an artificial blood vessel containing polyurethane;

[0080] S4, drying the artificial blood vessel containing polyurethane obtained in step S3 for 12 hours, then immersing it in pure water to remove impurities, taking it out, and drying it to obtain a leakage-proof artificial blood vessel.

[0081] See also Figure 3 The following are the tensile curves, shape, and tearing performance of the elastomer material prepared in Example 1 before and after soaking in saline. The elastomer was soaked for 24 hours (after 24 hours of swelling, the mass of the elastomer remained essentially unchanged and reached swelling equilibrium). It can be seen that after soaking in saline, the material still has good tensile properties and mechanical strength. Figure 3 As shown in a in FIG, it can be seen that after being immersed in physiological saline for 24 hours, the elastomer material can still maintain a strength of about 10 MPa.

[0082] Figure 4The in vitro and in vivo compatibility data for the elastomeric material prepared in Example 1 show that, like the control sample, the material has good cytocompatibility (using mouse fibroblasts), and no obvious inflammation was observed in the mouse tissues two weeks after subcutaneous implantation.

[0083] Figure 5 The in vitro and in vivo degradation diagram of the elastomeric material prepared in Example 1. After the elastomeric material prepared in Example 1 was placed on the back tissue of mice, the degradation performance of the material was observed and it was found that the material could be degraded well, as shown in FIG. Figure 5 As shown in Figure a. In addition, Figure 5 As shown in Figure b, the material degrades rapidly in PBS buffer, at a rate greater than that observed in vivo, indicating that lipase promotes the degradation of the elastomer. Overall, the results indicate that the material exhibits excellent degradation properties both in vitro and in vivo.

[0084] Figure 6 The hemolysis and coagulation properties of the elastomer extract were tested. Data showed that the hemolysis rate of the sample was less than 5%, meeting the standard for biomaterials used in humans. A higher coagulation value indicates more hemoglobin leakage and poorer coagulation performance. The resulting material exhibits poor coagulation properties, making it less likely to cause thrombosis and suitable for use as a coating material for artificial blood vessels to prevent thrombosis.

[0085] Comparative Example 1

[0086] Comparative Example 1 provides a method for preparing a leakage-proof artificial blood vessel. Compared with Example 1, the difference is that the solvent N'N-dimethylacetamide is not used in step S1, that is, only the solvent tetrahydrofuran is used. The rest is roughly the same as Example 1 and will not be repeated here.

[0087] The experiment showed that the first step of prepolymerization proceeded normally, but after the addition of oligosaccharides in the second step, the system became turbid and insoluble substances were present. It was later discovered that oligosaccharides were insoluble in tetrahydrofuran, and the reaction could not proceed normally under this system.

[0088] Comparative Example 2

[0089] Comparative Example 2 provides a method for preparing a leakage-proof artificial blood vessel. Compared with Example 1, the difference is that the solvent tetrahydrofuran is not used in step S1, that is, only the solvent N'N-dimethylacetamide is used. The rest is roughly the same as Example 1 and will not be repeated here.

[0090] The experiment showed that the overall reaction proceeded normally, but the mechanical properties of the resulting material were inferior to those obtained using a mixed solvent. The tensile strength was 8.2 MPa, and the tensile strain was 640%. This was likely due to the excessive amount of N'N-dimethylacetamide. The electrons on the nitrogen element of the solvent affected the catalytic activity of the dibutyltin dilaurate catalyst, thus affecting the polymerization process of the polyurethane.

[0091] Comparative Example 3

[0092] Comparative Example 3 provides a method for preparing a leakage-proof artificial blood vessel. Compared with Example 1, the difference is that the molecular weight of chitosan oligosaccharide is Mn=500. The rest is roughly the same as Example 1 and will not be repeated here.

[0093] Experiments show that the reaction can proceed normally under this system, but the resulting material is brittle and cannot be used normally. This may be because the molecular weight of the oligosaccharide is too small to form a good polyurethane network, resulting in the synthetic material being similar to brittle plastic.

[0094] Comparative Example 4

[0095] Comparative Example 4 provides a method for preparing a leakage-proof artificial blood vessel. Compared with Example 1, the difference is that in step S2, the reaction temperature is 60°C. The rest is roughly the same as Example 1 and will not be repeated here.

[0096] Experimental results indicate that the elastomer synthesis process proceeded normally, but the viscosity was thinner than when reacting at 40°C. The solution became darker yellow, accompanied by decomposition of the urethane bonds. After mold drying, the material became sticky and could not be molded properly. This is likely due to the depolymerization of the isocyanate and amino groups, which reduces the molecular weight and prevents molding.

[0097] Comparative Example 5

[0098] Comparative Example 5 provides a method for preparing a leakage-proof artificial blood vessel. Compared with Example 1, the difference is that the polyethylene glycol used is not dried to remove water. The rest is basically the same as Example 1 and will not be repeated here.

[0099] Experiments show that during the first step of the reaction, a large amount of bubbles are generated in the system, releasing a large amount of heat. This is caused by the reaction of isocyanate with water to produce carbon dioxide. As the reaction progresses, the system begins to gel, making it impossible to stir the rotor, and material synthesis cannot continue.

[0100] Comparative Example 6

[0101] Comparative Example 6 provides a method for preparing a leakage-proof artificial blood vessel. Compared with Example 1, the difference is that the molecular weight of the oligosaccharide is Mn=3000. The rest is roughly the same as Example 1 and will not be repeated here.

[0102] Experimental results indicate that while the first step of the reaction proceeded normally under these experimental conditions, the second, chain extension reaction, became difficult to stir after two hours and formed into a gel, preventing proper formation. This is because the molecular weight is too high, resulting in an increase in the number of functional groups reactive with isocyanate, which cross-links the molecular chain network and increases viscosity, preventing the rotor from stirring and halting material synthesis.

[0103] Examples 2-6 and Comparative Examples 7-8

[0104] Examples 2-6 and Comparative Examples 7-8 provide a method for preparing a leak-proof artificial blood vessel. The differences from Example 1 are that the amount of raw materials used in step S1, the amount of chitosan oligosaccharide used in step S2, and the molecular weight of the chitosan oligosaccharide used are changed, as shown in the table below. The remaining steps are substantially the same as those in Example 1 and are not described again herein.

[0105]

[0106] The elastomeric materials prepared in Examples 1-6 and Comparative Examples 7-8 were tested, and the results are shown in the following table.

[0107]

[0108] As can be seen from the above table, as the amount of chitosan oligosaccharide added increases, the water absorption rate gradually increases. When the amount of chitosan oligosaccharide added increases to 9%, the prepared elastomer material becomes sticky and cannot be molded, and cannot be used further, and subsequent tests cannot be performed. When the amount of chitosan oligosaccharide added is 0.5%, a small amount of oligosaccharide can be added to form, but the performance of the material is weak. The amount of chitosan oligosaccharide added needs to be 1%-8% of the mass of polyethylene glycol. Preferably, the amount of chitosan oligosaccharide added is 3%-6% of the mass of polyethylene glycol.

[0109] When the molecular weight used exceeds Mn=2500, gel coagulation is easily formed in the second step of the reaction and the chain cannot be extended normally, making it difficult for the reaction to proceed normally.

[0110] When the catalyst content was increased to 2% of the mass fraction of polyethylene glycol, the polymerization reaction was not greatly affected.

[0111] The anti-leakage performance of the prepared elastomer was compared with commercial collagen (source: bovine bone collagen) on the market, and the results are shown in the following table.

[0112]

[0113] It can be seen from the above table that with the increase in the amount of chitosan oligosaccharide, the permeability shows a gradually increasing trend, which may be due to the increase in the hydrophilicity of the system, but overall it shows good anti-permeation performance.

[0114] It should be noted that the present application is not limited to the above-mentioned embodiments. The above-mentioned embodiments are merely examples, and any embodiments having substantially the same structure and effect as the technical concept within the scope of the present application are all included in the technical scope of the present application. In addition, without departing from the scope of the present application, any other embodiments that can be conceived by those skilled in the art and that combine some of the constituent elements in the embodiments are also included in the scope of the present application.

Claims

1. A method for preparing an elastomeric material, characterized in that: The following steps are involved: S1, dissolving dried and dehydrated polyethylene glycol, hexamethylene diisocyanate, and dibutyltin dilaurate in a mixture of a first solvent and tetrahydrofuran, and reacting in an oil bath at 50-80°C for 3-24 hours to obtain a precursor solution; the first solvent is N'N-dimethylacetamide or DMF; and the volume ratio of the first solvent to tetrahydrofuran in the mixture of the first solvent and tetrahydrofuran is (4-6):(6-4); S2. Adding a chain extender, chitosan oligosaccharide, dissolved in N'N-dimethylacetamide, to the precursor solution obtained in step S1 and continuing the reaction for 4-24 hours at a reaction temperature of 20-50° C. to obtain a polyurethane elastomer solution; the amount of the chitosan oligosaccharide is 1%-8% of the mass of the polyethylene glycol; and the number average molecular weight of the chitosan oligosaccharide is 1000-2500.

2. The method for preparing an elastomeric material according to claim 1, wherein: In step S1, the molar ratio of polyethylene glycol to hexamethylene diisocyanate is 1:(2-2.4).

3. The method for preparing an elastomeric material according to claim 1, wherein: The amount of dibutyltin dilaurate used is 1%-2% of the mass of polyethylene glycol.

4. A method for preparing a leak-proof artificial blood vessel, characterized in that: The polyurethane elastomer solution prepared using any one of claims 1 to 3 comprises the following steps: S3, placing the artificial blood vessel into the polyurethane elastomer solution for extraction; or spraying the polyurethane elastomer solution onto the artificial blood vessel to obtain an artificial blood vessel containing polyurethane; S4, drying the artificial blood vessel containing polyurethane obtained in step S3 for 4-24 hours, then immersing it in pure water to remove impurities, taking it out and drying it to obtain a leakage-proof artificial blood vessel.

5. The method for preparing the leakage-proof artificial blood vessel according to claim 4, characterized in that: The artificial blood vessel is an artificial blood vessel woven from polyester or PTFE.

6. A leak-proof artificial blood vessel, characterized in that: The anti-leakage artificial blood vessel is prepared by the preparation method according to any one of claims 4-5, comprising an artificial blood vessel matrix and a polyurethane anti-leakage coating supported on the surface of the artificial blood vessel matrix; the thickness of the polyurethane anti-leakage coating is 0.1-0.5 mm; the tensile strength of the anti-leakage artificial blood vessel is greater than or equal to 19 MPa, and the tear resistance can reach 162 kJ m -2 .

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