Expanded polytetrafluoroethylene artificial blood vessel with anticoagulation coating as well as preparation and application of expanded polytetrafluoroethylene artificial blood vessel

Abstract

According to the scheme, the expanded polytetrafluoroethylene artificial blood vessel with the anticoagulant coating and preparation and application are provided, firstly, groups such as carboxyl and amino are formed on the inner surface of the expanded polytetrafluoroethylene artificial blood vessel through co-auto-polymerization reaction of L-dopamine and polyethyleneimine in a Tris aqueous alkali, then epoxy chloropropane serves as a cross-linking agent, and the expanded polytetrafluoroethylene artificial blood vessel with the anticoagulant coating is prepared. Trihydroxymethyl methylamino propanesulfonic acid is cross-linked to the inner surface of the membrane, carboxyl and sulfonic acid groups on the surface of the membrane endow the expanded polytetrafluoroethylene artificial blood vessel with anticoagulation performance, meanwhile, the hydrophobic performance of the outer surface is reserved, anticoagulation finishing is conducted on the inner wall of the expanded polytetrafluoroethylene artificial blood vessel, and the hydrophobic performance of the outer wall of the blood vessel is reserved; the expanded polytetrafluoroethylene artificial blood vessel has an anticoagulation function and does not influence the growth of fiber cells and fiber connective tissues on the surface of the blood vessel.

Description

Technical Field

[0001] The present invention relates to the field of artificial blood vessel coatings, and particularly to an expanded polytetrafluoroethylene artificial blood vessel with an anticoagulant coating, and its preparation and application. Background Art

[0002] Due to its significant advantages such as high porosity, high mechanical strength, low cost, and no toxicity to the human body, the polytetrafluoroethylene microporous membrane has been widely used in the field of artificial blood vessels. The high porosity provides a suitable space for the adhesion and growth of cells, which helps the repair and reconstruction of tissues; the high mechanical strength enables it to withstand the pressure during human blood circulation and maintain the normal shape and function of blood vessels; the low price is conducive to reducing medical costs and improving the accessibility of artificial blood vessels; and the non-toxicity to the human body ensures the safety of human use.

[0003] However, the polytetrafluoroethylene microporous membrane has some defects that cannot be ignored. Its surface tension is small and its surface wettability is poor, which makes it have strong hydrophobicity. When an artificial blood vessel made of this material is implanted into the human body and comes into contact with blood, components such as proteins and platelets in the blood are likely to adsorb and aggregate on its surface, thereby triggering a coagulation reaction. Once the coagulation reaction occurs, thrombus may be generated. The thrombus will block the blood vessel and affect the normal flow of blood, resulting in insufficient blood supply to organs and causing serious health problems. In addition, there may also be abnormal intimal hyperplasia, which makes the blood vessel lumen narrower, further reducing the blood flow efficiency, and ultimately leading to a low long-term patency rate after transplantation. This makes it difficult for the polytetrafluoroethylene microporous membrane to continuously and effectively play its role during the long-term use of replacing human blood vessels, restricting its application effect in clinical treatment.

[0004] At present, although there has been some progress in the research on the anticoagulant coating of the polytetrafluoroethylene microporous membrane, many challenges still remain. For example, Patent CN106729998A reports a coating for the inner wall of an artificial blood vessel modified with mussel adhesive protein and its preparation method. Mussel adhesive protein is first used to modify a bio-artificial blood vessel to construct a bio-artificial blood vessel with an anti-thrombosis function. However, the extraction process of mussel adhesive protein is quite difficult. Mussel adhesive protein usually needs to be obtained from marine organisms such as mussels. Its extraction process is complex and the yield is limited, which leads to difficulties in large-scale production and is difficult to meet the large demand for artificial blood vessels in clinical practice, restricting the wide application of this technology.

[0005] Patent CN208974736U proposed a method for preparing a silk fibroin-modified artificial blood vessel. By using silk fibroin to modify the artificial blood vessel, a blood vessel coating with anticoagulant properties was constructed. However, this preparation process uses low-temperature plasma treatment technology, which has high requirements for equipment and complex operation processes. It not only increases the preparation cost but also has high requirements for the professional skills of operators, is not conducive to large-scale industrial production, and hinders the popularization and application of this technology to a certain extent.

[0006] Patent CN111793232A first synthesizes phosphorylcholine containing amino groups and phosphorylcholine polymers containing carboxyl groups, and then uses dopamine as a cross-linking agent to cross-link the amino and carboxyl groups in the two substances, relying on the phosphorylcholine groups in the polymer to achieve the anticoagulant function. However, when synthesizing amino phosphorylcholine and carboxyl phosphorylcholine polymers, self-polymers are likely to be produced in the products, such as polymethacrylic acid, 2-aminoethyl methacrylate, etc. These self-polymers are difficult to effectively separate. Once they remain in the final product, they may cause certain pollution to the blood, affect the normal physiological functions of the blood, and bring potential risks to clinical applications.

[0007] In summary, developing a polytetrafluoroethylene microporous membrane anticoagulant coating that not only has excellent anticoagulant performance but also can ensure convenient material acquisition, simple preparation process, and low cost has become an urgent problem to be solved in the current field of artificial blood vessels, which is of great significance for improving the clinical application effect of artificial blood vessels and promoting the development of cardiovascular disease treatment technologies. Summary of the Invention

[0008] The purpose of the present invention is to provide an expanded polytetrafluoroethylene artificial blood vessel with an anticoagulant coating and its preparation and application. By performing anticoagulant finishing on the inner wall of the expanded polytetrafluoroethylene artificial blood vessel and retaining the hydrophobic properties of the outer wall of the blood vessel, the expanded polytetrafluoroethylene artificial blood vessel has anticoagulant function without affecting the growth of fibroblast cells and fibrous connective tissue on the surface of the blood vessel.

[0009] To achieve the above purpose, the present technical solution provides a method for preparing an expanded polytetrafluoroethylene artificial blood vessel with an anticoagulant coating, including:

[0010] 1) Dissolve L-dopamine and polyethyleneimine in Tris alkaline solution to prepare a reaction solution;

[0011] 2) Moisten the expanded polytetrafluoroethylene artificial blood vessel with ethanol, and use a peristaltic pump to circulate and inject the reaction solution into the expanded polytetrafluoroethylene artificial blood vessel at a pressure below the ethanol bubble point;

[0012] 3) Wash the expanded polytetrafluoroethylene artificial blood vessel with deionized water, and pour the epichlorohydrin / tris(hydroxymethyl)methylaminopropanesulfonic acid aqueous solution into the tube film of the expanded polytetrafluoroethylene artificial blood vessel;

[0013] 4) Seal both ends of the expanded polytetrafluoroethylene artificial blood vessel and place it in an air shaker for reaction, then take it out;

[0014] 5) Wash the expanded polytetrafluoroethylene artificial blood vessel and then dry it to obtain an expanded polytetrafluoroethylene artificial blood vessel with an anticoagulant coating.

[0015] In this solution, first, through the co-self-polymerization reaction of levodopa and polyethyleneimine in a Tris base solution, groups such as carboxyl and amino groups are formed on the inner surface of the expanded polytetrafluoroethylene artificial blood vessel. Then, using epichlorohydrin as a cross-linking agent, 3-(trimethylammonio)-1-propanesulfonate is cross-linked on the inner surface of the membrane of the expanded polytetrafluoroethylene artificial blood vessel. The carboxyl and sulfonic acid groups on the membrane surface endow the expanded polytetrafluoroethylene artificial blood vessel with anticoagulant properties, while retaining the hydrophobic properties of the outer surface.

[0016] In other words, this solution only conducts anticoagulant finishing on the inner wall of the expanded polytetrafluoroethylene artificial blood vessel. A large number of carboxyl and sulfonic acid groups endow the expanded polytetrafluoroethylene artificial blood vessel with strong anticoagulant properties, while retaining the hydrophobic properties of the outer surface of the expanded polytetrafluoroethylene artificial blood vessel, so that the expanded polytetrafluoroethylene artificial blood vessel has anticoagulant function without affecting the growth of fibroblasts and fibrous connective tissue on the blood vessel surface.

[0017] In some embodiments, in step (1), the concentration of levodopa is 1 - 10 g / L, the concentration of polyethyleneimine is 1 - 10 g / L, and the pH value of Tris base is 8.5. Levodopa and polyethyleneimine will undergo a co-self-polymerization reaction in a Tris alkaline solution environment. Appropriate concentrations of levodopa and polyethyleneimine can ensure that there are sufficient reaction monomers participating in the polymerization to form a sufficient number of active groups. If the concentration is too low, the reaction degree is insufficient, resulting in a small number of active groups, which will affect the subsequent anticoagulant properties. If the concentration is too high, the reaction may be too intense to control, and even adverse phenomena such as agglomeration may occur. The environment with a Tris base pH value of 8.5 provides a stable alkaline condition for the co-self-polymerization reaction.

[0018] It should be noted that the expanded polytetrafluoroethylene itself has strong hydrophobicity, resulting in difficulty for the reaction solution to be evenly dispersed and penetrate when it directly contacts the reaction solution. Ethanol can reduce the surface tension of the blood vessel material, enabling the subsequent reaction solution to better contact the inner surface of the blood vessel and ensuring full reaction. Circulating and injecting the reaction solution below the ethanol bubble point pressure of the expanded polytetrafluoroethylene artificial blood vessel is to avoid generating bubbles. If the injection pressure is higher than the bubble point pressure, gas may form bubbles in the blood vessel, which will affect the full contact between the reaction solution and the inner surface of the blood vessel, hinder the normal progress of the reaction, and may also form defects in the coating, affecting the quality and performance of the anticoagulant coating.

[0019] In some embodiments, in step (2), the in-tube circulation time is 5 - 10 h, and the temperature is 37 °C. This solution sets a sufficiently long reaction time to ensure that components such as levodopa and polyethyleneimine in the reaction solution have sufficient time to undergo a co-self-polymerization reaction on the inner surface of the blood vessel, forming more active groups such as carboxyl and amino groups with anticoagulant functions.

[0020] In some embodiments, in step (3), the concentration of epichlorohydrin is 0.1 - 0.5 g / L, and the concentration of 3-(N-morpholino)propanesulfonic acid is 1 - 10 g / L.

[0021] It should be noted that epichlorohydrin acts as a cross-linking agent in the reaction. It contains active epoxy groups that can react with groups such as carboxyl and amino groups formed on the inner surface of the expanded polytetrafluoroethylene artificial blood vessel before, and interact with groups such as hydroxyl groups in the subsequent 3-(N-morpholino)propanesulfonic acid, thereby cross-linking 3-(N-morpholino)propanesulfonic acid to the inner surface of the blood vessel. Its concentration is controlled at 0.1 - 0.5 g / L. If the concentration is too low, the degree of cross-linking is insufficient, and 3-(N-morpholino)propanesulfonic acid cannot be firmly connected to the inner surface of the blood vessel, which will affect the stability and durability of the anticoagulant coating; if the concentration is too high, it may lead to excessive cross-linking, making the coating structure too tight, affecting its flexibility and biocompatibility, and may also introduce more impurities, having an adverse impact on blood compatibility.

[0022] The 3-(N-morpholino)propanesulfonic acid molecule contains functional groups such as sulfonic acid groups, which endow the expanded polytetrafluoroethylene artificial blood vessel with anticoagulant properties. Its concentration is between 1 - 10 g / L. When the concentration is relatively low, the number of anticoagulant functional groups provided is insufficient, and the anticoagulant effect is not obvious; when the concentration is too high, it may lead to too high a surface charge density of the coating, affecting the normal behavior of components such as proteins and cells in the blood, which is also not conducive to the optimization of anticoagulant performance and may also increase production costs.

[0023] In some embodiments, in step (4), the reaction temperature is 37 °C, the reaction time is 2 - 6 h, and the rotational speed of the air shaker is 120 rpm. The rotational speed of the air shaker is set at 120 rpm, which can provide an appropriate oscillation intensity. When the rotational speed is too low, the flow and mixing of the reaction solution are not sufficient, which may lead to uneven local reactions and affect the quality of the coating. When the rotational speed is too high, it may cause mechanical damage to the blood vessel material and the partially formed coating, destroying the structure and integrity of the coating, and may also cause excessive foaming or splashing of the reaction solution, affecting the normal progress of the reaction. Therefore, a rotational speed of 120 rpm can ensure the full mixing and flow of the reaction solution while avoiding unnecessary damage to the blood vessel and the coating.

[0024] In some embodiments, in step (5), the expanded polytetrafluoroethylene artificial blood vessel is washed with deionized water and absolute ethanol and then dried, and the drying temperature is 60°C.

[0025] In a second aspect, the present solution provides an expanded polytetrafluoroethylene artificial blood vessel with an anticoagulant coating, which is prepared according to the preparation method of the expanded polytetrafluoroethylene artificial blood vessel with an anticoagulant coating mentioned in the first aspect above, and carboxyl groups and sulfonic acid groups are attached to the inner surface.

[0026] In some embodiments, the expanded polytetrafluoroethylene artificial blood vessel can be applied in the fields of blood vessel implantation and cardiovascular disease treatment.

[0027] Compared with the prior art, the present technical solution has the following characteristics and beneficial effects:

[0028] In this solution, L-dopamine and polyethyleneimine co-self-polymerize in a Tris base solution, and epichlorohydrin crosslinks 3-(trimethylammonio)propanesulfonate to introduce a large number of carboxyl groups and sulfonic acid groups on the inner surface of the blood vessel. These groups endow the blood vessel with strong anticoagulant ability, effectively reduce the coagulation risk, improve the blood compatibility of the artificial blood vessel in vivo, reduce the possibility of thrombosis and abnormal intimal hyperplasia, and ensure the long-term patency after blood vessel transplantation. Moreover, this solution retains the hydrophobic property of the outer wall of the blood vessel and does not affect the growth of fibroblasts and fibrous connective tissue on the surface of the blood vessel, which enables the artificial blood vessel to better fuse with the surrounding tissues after being implanted into the human body, promotes tissue repair and blood vessel regeneration, avoids inflammation or other adverse reactions caused by tissue incompatibility, and improves the long-term stability and functionality of the artificial blood vessel.

[0029] In addition, the preparation method of this solution is relatively simple, the raw materials are widely available, and the cost is relatively low. Compared with the traditional technology, it avoids complex extraction or synthesis processes and does not require special equipment, such as the difficult extraction of mussel adhesive protein and the need for low-temperature plasma treatment for silk fibroin modification. It is conducive to large-scale industrial production, increases the output of artificial blood vessels, reduces medical costs, and benefits more patients. The prepared expanded polytetrafluoroethylene artificial blood vessel with an anticoagulant coating can be applied in the fields of blood vessel implantation and cardiovascular disease treatment. It can meet different clinical needs, provide a safer and more effective treatment means for cardiovascular disease patients, and promote the development of cardiovascular disease treatment technology. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 is a schematic diagram of the chemical reaction of the anticoagulant coating of the present invention;

[0031] Figure 2 is a static water contact angle diagram of the inner surface of the sample in Example 2 of the present invention;

[0032] Figure 3 is a static water contact angle diagram of the outer surface of the sample in Example 2 of the present invention;

[0033] Figure 4 Static water contact angle diagram of the inner surface of the sample in Comparative Example 1 of the present invention;

[0034] Figure 5 Static water contact angle diagram of the outer surface of the sample in Comparative Example 2 of the present invention. Detailed implementation manners

[0035] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention belong to the scope of protection of the present invention.

[0036] Those skilled in the art should understand that in the disclosure of the present invention, the orientation or positional relationships indicated by the terms "longitudinal", "lateral", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", etc. are based on the orientation or positional relationships shown in the drawings. These are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation. Therefore, the above terms should not be construed as limiting the present invention.

[0037] In the present invention, first, carboxyl, amino and other groups are formed on the inner surface of the expanded polytetrafluoroethylene artificial blood vessel through the co-self-polymerization reaction of L-dopamine and polyethyleneimine in Tris base solution. Then, using epichlorohydrin as a cross-linking agent, 3-(N-morpholino)propanesulfonic acid is cross-linked on the inner surface of the membrane. The carboxyl and sulfonic acid groups on the membrane surface endow the expanded polytetrafluoroethylene artificial blood vessel with anticoagulant properties, while retaining the hydrophobic properties of the outer surface.

[0038] Example 1:

[0039] 1) Dissolve 1 g of L-dopamine and 10 g of polyethyleneimine in 1 L of Tris alkaline solution with a pH of 8.5 to prepare a reaction solution;

[0040] 2) First, infiltrate the expanded polytetrafluoroethylene artificial blood vessel with ethanol, and then use a peristaltic pump to circulate and inject the reaction solution into the tube at a pressure lower than the ethanol bubble point pressure of the polytetrafluoroethylene tube membrane. The circulation time inside the tube is 10 h, and the temperature is 37 °C;

[0041] 3) Wash the expanded polytetrafluoroethylene artificial blood vessel with deionized water, and then pour the epichlorohydrin and 3-(N-morpholino)propanesulfonic acid aqueous solution into the tube membrane. The concentration of epichlorohydrin is 0.1 g / L, and the concentration of 3-(N-morpholino)propanesulfonic acid is 1 g / L;

[0042] 4) Seal both ends of the expanded polytetrafluoroethylene artificial blood vessel and place it in an air shaker at a temperature of 37°C and a rotation speed of 120 rpm for a reaction time of 6 h;

[0043] 5) Wash the expanded polytetrafluoroethylene artificial blood vessel successively with deionized water and absolute ethanol, and dry it at 60°C to obtain an expanded polytetrafluoroethylene artificial blood vessel with an anticoagulant coating.

[0044] Example 2:

[0045] 1) Dissolve 5 g / L of L-dopamine and 5 g / L of polyethyleneimine in a Tris alkaline solution with a pH of 8.5 to prepare 1 L of reaction solution;

[0046] 2) First, soak the expanded polytetrafluoroethylene artificial blood vessel with ethanol, and then use a peristaltic pump to circulate and inject the reaction solution into the tube at a pressure lower than the ethanol bubble point pressure of the polytetrafluoroethylene tube membrane for flow. The in-tube circulation time is 8 h, and the temperature is 37°C;

[0047] 3) Wash the expanded polytetrafluoroethylene artificial blood vessel with deionized water, and then pour an aqueous solution of epichlorohydrin and 3-(N-morpholino)propanesulfonic acid into the tube membrane. The concentration of epichlorohydrin is 0.3 g / L, and the concentration of 3-(N-morpholino)propanesulfonic acid is 5 g / L;

[0048] 4) Seal both ends of the expanded polytetrafluoroethylene artificial blood vessel and place it in an air shaker at a temperature of 37°C and a rotation speed of 120 rpm for a reaction time of 4 h;

[0049] 5) Wash the expanded polytetrafluoroethylene artificial blood vessel successively with deionized water and absolute ethanol, and dry it at 60°C to obtain an expanded polytetrafluoroethylene artificial blood vessel with an anticoagulant coating.

[0050] Example 3:

[0051] 1) Dissolve 10 g of L-dopamine and 1 g of polyethyleneimine in a Tris alkaline solution with a pH of 8.5 to prepare 1 L of reaction solution;

[0052] 2) First, soak the expanded polytetrafluoroethylene artificial blood vessel with ethanol, and then use a peristaltic pump to circulate and inject the reaction solution into the tube at a pressure lower than the ethanol bubble point pressure of the polytetrafluoroethylene tube membrane for flow. The in-tube circulation time is 5 h, and the temperature is 37°C;

[0053] 3) Wash the expanded polytetrafluoroethylene artificial blood vessel with deionized water, and then pour an aqueous solution of epichlorohydrin and 3-(N-morpholino)propanesulfonic acid into the tube membrane. The concentration of epichlorohydrin is 0.5 g / L, and the concentration of 3-(N-morpholino)propanesulfonic acid is 10 g / L;

[0054] 4) Seal both ends of the expanded polytetrafluoroethylene artificial blood vessel and place it in an air shaker at a temperature of 37°C and a rotation speed of 120 rpm for a reaction time of 2 h;

[0055] 5) The expanded polytetrafluoroethylene artificial blood vessel was successively cleaned with deionized water and absolute ethanol, and dried at 60 °C to obtain an expanded polytetrafluoroethylene artificial blood vessel with an anticoagulant coating.

[0056] Comparative Example 1:

[0057] An untreated expanded polytetrafluoroethylene artificial blood vessel.

[0058] Anticoagulant performance test:

[0059] The activated partial thromboplastin time (APTT) and thrombin time (TT), which are regarded as two important indicators clinically, were adopted. Measured with a coagulation analyzer (PUN-2048A) Clotting time . APTT During the test, first, 0.1 mL of plasma was placed in a test cup, then the membrane (1.0 cm × 1.0 cm) was folded into a suitable size and stuffed into the bottom of the solution. After that, the same volume of APTT reagent was sprayed into the mixture with a pipette. After incubating at 37 °C for 5 minutes, 0.1 mL of CaCl2 (0.025 mol·mL -1 ) was quickly added to the mixture. Then, the APTT value was determined when the first coagulation occurred. Clotting time Finally, it was obtained from the average value of three measurements. For the TT test, first, 0.2 mL of plasma was injected into the test cup, then the sample (1.0 cm × 1.0 cm) was immersed in the plasma. After incubating at 37 °C for 5 minutes in the coagulation analyzer, an equal amount of TT reagent was dropped into the test cup. The TT value was determined by that of PPP Clotting time , and the coagulation time was also proved by the average value of 3 inspections.

[0060] Antiprotein adsorption performance test:

[0061] By dissolving bovine serum albumin (BSA) in physiological In saline to prepare a 1.0 g·L -1 BSA solution. Before the test, all samples were circulated with pure water under a pressure of 0.1 MPa until a stable water flow was obtained. After reaching a stable flux, physiological saline was used instead of pure water. Then, the volume of the permeate at the outlet end was measured every 5 minutes and continuously measured for 25 minutes in the same way. Subsequently, the pre-prepared BSA solution was used instead of physiological saline, and the detection was repeated again. After one cycle, the test samples were washed with deionized water for 40 minutes to wash off the adhered protein, and then the test was repeated with physiological saline for 25 minutes. The test results were expressed by the ultrafiltration rate (UFR):

[0062]

[0063] where UFR (L·m -2 ·h-1 ·mmHg -1 ) represents the ultrafiltration rate of water, S(m 2 ) represents the sample in the effective measurement area, t(h) is the measurement time, P is the transmembrane pressure, and V(L) represents the volume of the permeate. The anti-protein adsorption performance is obtained by the ratio of the ultrafiltration rate of physiological saline before and after cleaning the membrane, which is called the flux recovery rate.

[0064] The test results of the performance tests for each example and comparative example are shown in Table 1 below:

[0065] Table 1 Performance test table of each example and comparative example

[0066]

[0067] As can be seen from Table 1, the anti-thrombogenic expanded polytetrafluoroethylene artificial blood vessel obtained by the method of the present invention not only has good anti-thrombogenicity, but also has high anti-pollution performance against bovine serum albumin. The flux recovery rate of physiological saline is more than 90%, and the APTT and TT times in the coagulation test are greatly extended.

[0068] Figure 1 This is a schematic diagram of the chemical reaction of the anti-thrombogenic coating of the present invention. After a series of chemical reactions, a large number of anticoagulant functional groups such as carboxyl groups and sulfonic acid groups are generated on the membrane surface. Figure 2 This is a diagram of the static water contact angle of the inner surface of the sample in Example 2 of the present invention. Figure 3 This is a diagram of the static water contact angle of the outer surface of the sample in Example 2 of the present invention. Figure 4 This is a diagram of the static water contact angle of the inner surface of the sample in Comparative Example 1 of the present invention. Figure 5 This is a diagram of the static water contact angle of the outer surface of the sample in Comparative Example 2 of the present invention. Compared with the untreated one, the water contact angle of the membrane surface of the anti-thrombogenic polytetrafluoroethylene artificial blood vessel obtained by the present invention is greatly reduced, and the hydrophilicity of the membrane is greatly increased; for the outer wall, the surface water contact angle basically does not change, indicating that the method of the present invention retains the hydrophobicity of the outer wall.

[0069] Those skilled in the art should understand that the technical features of the above embodiments can be combined arbitrarily. For the sake of brevity of description, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, it should be considered as the scope described in this specification.

[0070] The above embodiments merely represent several implementation manners of the present application. The description thereof is relatively specific and detailed, but it should not be construed as a limitation on the scope of the present application. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present application, several modifications and improvements can still be made, and these all fall within the protection scope of the present application. Therefore, the protection scope of the present application shall be subject to the appended claims.

Claims

1. A preparation method of an expanded polytetrafluoroethylene artificial blood vessel with an anticoagulant coating, characterized in that, Including: 1) Dissolve L-dopamine and polyethyleneimine in Tris alkaline solution to prepare a reaction solution; 2) Soak the expanded polytetrafluoroethylene artificial blood vessel with ethanol, and use a peristaltic pump to circulate and inject the reaction solution into the expanded polytetrafluoroethylene artificial blood vessel under a pressure lower than the ethanol bubble point; 3) Wash the expanded polytetrafluoroethylene artificial blood vessel with deionized water, and pour the epichlorohydrin / tris(hydroxymethyl)methylaminopropanesulfonic acid aqueous solution into the tube membrane of the expanded polytetrafluoroethylene artificial blood vessel; 4) Seal both ends of the expanded polytetrafluoroethylene artificial blood vessel and place it in an air shaker for reaction and then take it out; 5) Wash the expanded polytetrafluoroethylene artificial blood vessel and then dry it to obtain an expanded polytetrafluoroethylene artificial blood vessel with an anticoagulant coating.

2. The preparation method of the expanded polytetrafluoroethylene artificial blood vessel with an anticoagulant coating according to claim 1, characterized in that, In step (1), the concentration of L-dopamine is 1-10 g / L, the concentration of polyethyleneimine is 1-10 g / L, and the pH value of Tris base is 8.

5.

3. The preparation method of the expanded polytetrafluoroethylene artificial blood vessel with an anticoagulant coating according to claim 1, characterized in that, In step (2), the in-tube circulation time is 5-10 h, and the temperature is 37 °C.

4. The preparation method of the expanded polytetrafluoroethylene artificial blood vessel with an anticoagulant coating according to claim 1, characterized in that, In step (3), the concentration of epichlorohydrin is 0.1-0.5 g / L, and the concentration of tris(hydroxymethyl)methylaminopropanesulfonic acid is 1-10 g / L.

5. The preparation method of the expanded polytetrafluoroethylene artificial blood vessel with an anticoagulant coating according to claim 1, wherein, In step (4), the reaction temperature is 37 °C, the reaction time is 2-6 h, and the rotational speed of the air shaker is 120 rpm.

6. The preparation method of the expanded polytetrafluoroethylene artificial blood vessel with an anticoagulant coating according to claim 1, characterized in that, In step (5), wash the expanded polytetrafluoroethylene artificial blood vessel with deionized water and absolute ethanol and then dry it. The drying temperature is 60 °C.

7. An expanded polytetrafluoroethylene artificial blood vessel with an anticoagulant coating, characterized in that, Prepared according to the preparation method of the expanded polytetrafluoroethylene artificial blood vessel with an anticoagulant coating described in any one of claims 1 to 6 above, with carboxyl groups and sulfonic groups attached to the inner surface.

8. The expanded polytetrafluoroethylene artificial blood vessel with an anticoagulant coating according to claim 7, characterized in that, Applied in the fields of blood vessel implantation and cardiovascular disease treatment.

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