Composite material having anticoagulant property, preparation method therefor, and use thereof

Abstract

The present application provides a composite material having an anticoagulant property, a preparation method therefor, and use thereof. The composite material is prepared by sequentially preparing a dip coating layer and a coating layer on the surface of a fabric substrate and further grafting zwitterions having an anticoagulant function. In the described process, using fabric as the substrate can impart the softness, elasticity, and other characteristics of fabric to the composite material, so that the composite material is more suitable for use as a biomedical material; the dip coating layer is subjected to chemical microetching to form a microporous structure on the surface of the dip coating layer. Secondly, during chemical microetching, polymer side chains can be opened, and oxygen-containing free radicals are formed in the surface of the dip coating layer and chemically crosslinked to the zwitterions in the coating layer.

Description

Composite material with anticoagulant property and preparation method and application thereof TECHNICAL FIELD

[0001] The present application relates to the technical field of cardiovascular medical devices, and particularly relates to a composite material with anticoagulant property and a preparation method and application thereof. BACKGROUND

[0002] Valvular heart disease (VHD) refers to the occurrence of lesions in one or more valves of the heart due to rheumatic fever, mucovariation, degeneration, congenital malformation, ischemic necrosis, infection or trauma, etc. The diseased valve has structural changes or abnormal activity, causing the valve to open or close, resulting in valve stenosis or regurgitation, affecting the normal flow of blood, and causing abnormal heart function, and eventually leading to heart failure. According to reports, the prevalence rate of moderate to severe disease in the population aged 18-44 is 0.7%, and the prevalence rate of moderate to severe disease in the population aged 75 and above is 13.3%. At present, the most common treatment for VHD is heart valve replacement, using mechanical or biological valves. Globally, there are about 250,000 to 300,000 cases of valve replacement per year, of which about 55% are implanted with mechanical valves and about 45% are implanted with biological valves.

[0003] Mechanical valves have excellent durability, but high shear stress can easily lead to thrombosis, and patients implanted with mechanical valves need lifelong anticoagulant therapy. Patients implanted with biological valves also need short-term anticoagulation, and commercially available biological heart valves are generally prepared by glutaraldehyde crosslinking of pig pericardium, bovine pericardium, etc., and have the problem of easy calcification, which makes the valve rigid, reduces the opening and closing function, causes stenosis or regurgitation, and results in a limited lifespan.

[0004] Polymer valves have excellent mechanical strength and fatigue resistance, as well as the required flexibility, biocompatibility and anti-calcification. Compared with biological valves, polymer valves can be implanted in patients of any age group. A variety of high molecular polymers with biocompatibility and biostability can be used for polymer valves, but anticoagulation is still a problem to be solved. In the past decade, a large number of research reports have reported the development of ideal polymer valves, but the focus is on valve design, and little attention is paid to the properties of the material itself. It is of great significance to develop a high molecular leaflet material with good biocompatibility and mechanical strength, and excellent long-term anticoagulant property.

[0005] Therefore, it is necessary to design an improved composite material with anticoagulant property to solve the above problems. SUMMARY

[0006] The present application aims to provide a composite material with anticoagulant property and a preparation method and application thereof.

[0007] To achieve the above-mentioned application purposes, the application provides a preparation method of a composite material with anticoagulation performance, comprising the following steps:

[0008] S1, immersing a fabric into a first polymer solution to obtain a fabric with at least two immersion coating layers formed on the surface of the fabric;

[0009] S2, immersing the fabric with the immersion coating layers obtained in step S1 into a MnO2-H3PO4-H2O ternary micro-etching system solution to etch the immersion coating layers and form immersion coating layers with micro-porous structures; then, coating a second polymer solution containing zwitterions on the surface of at least one immersion coating layer with micro-porous structures, i.e. forming a coating layer on the surface of the immersion coating layer; after drying, performing a catalytic reaction to obtain the composite material.

[0010] As an embodiment of the application, in step S2, the second polymer solution containing zwitterions is prepared by dispersing zwitterionic monomers in a second polymer solution, the mass-volume fraction of the second polymer solution is 5-30%, and the zwitterionic monomers are one or more of 2-[(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide, methacrylic acid carboxybetaine and 2-methacryloyloxyethylphosphocholine, and the volume fraction of the zwitterionic monomers is 3-30%.

[0011] As an embodiment of the application, in step S2, the concentration of MnO2 in the MnO2-H3PO4-H2O ternary micro-etching system solution is 1-10 g / L, and the ratio of V(H3PO4) / V(H2O) is 1-5.

[0012] As an embodiment of the application, in step S2, the fabric is immersed in the ternary micro-etching system solution for 1-20 min at a temperature of 20-60℃, and the catalytic reaction is performed at a temperature of 60-80℃ for 6-96 h.

[0013] As an embodiment of the application, in step S1, the mass-volume fraction of the first polymer solution is 5-30%, the solute of the first polymer solution and / or the second polymer solution is a polyurethane polymer, the polyurethane polymer is one or more of a polyether type polyurethane, a polyurethane urea, a polycarbonate type polyurethane and a polysiloxane polyurethane, and the solvent of the first polymer solution and / or the second polymer solution is one or more of N,N-dimethylacetamide, toluene, tetrahydrofuran, acetone and dichloromethane.

[0014] As an embodiment of the present application, in step S1, the material of the fabric comprises one or more of polyethylene terephthalate, polyethylene, polylactic acid, polypropylene, polyvinyl chloride, polytetrafluoroethylene; the soaking time of the fabric in the first polymer solution is 60-400s.

[0015] Further, the composite material prepared by the preparation method comprises:

[0016] a fabric;

[0017] at least two dip-coating layers formed on the surface of the fabric;

[0018] two coating layers formed on the surface of the distal dip-coating layer of the fabric, and a microporous structure is formed on the side of the dip-coating layer close to the coating layer, and at least a part of the coating layer is embedded in the microporous structure.

[0019] In particular, the composite material prepared by the preparation method of the present application can be applied in the field of biomedical materials. As an embodiment of the present application, an artificial heart valve is provided, comprising a stent and a plurality of leaflets attached to the stent, wherein the leaflets comprise the composite material prepared by the above method. Further, the artificial heart valve further comprises a skirt arranged on the stent, and the skirt comprises the composite material prepared by the above method. BRIEF DESCRIPTION OF DRAWINGS

[0020] FIG. 1 is an SEM image of the composite material with anticoagulant properties prepared in Example 1 of the present application;

[0021] FIG. 2 is a micro-etching structure in the preparation process of the composite material of Example 1 of the present application;

[0022] FIG. 3 is a comparison diagram of the surface water contact angle of the leaflets prepared in Example 1 and Comparative Example 1 of the present application;

[0023] FIG. 4 is a comparison diagram of the surface fibrinogen adsorption of the leaflets prepared in Example 1 and Comparative Example 1 of the present application;

[0024] FIG. 5 is a comparison diagram of the surface platelet adhesion of the leaflets prepared in Example 1 and Comparative Example 1 of the present application;

[0025] FIG. 6 is a comparison diagram of the surface platelet adhesion of the leaflets prepared in Example 1 and Comparative Example 1 of the present application after in-vitro accelerated fatigue test;

[0026] FIG. 7 is a comparison diagram of the surface platelet adhesion of the leaflets prepared in Comparative Example 2 of the present application after in-vitro accelerated fatigue test. DETAILED DESCRIPTION

[0027] In order to make the purposes, technical solutions and advantages of the present application clearer, the present application will be described in detail below with reference to the drawings and specific embodiments.

[0028] It should also be noted that, in order to avoid obscuring the present application due to unnecessary details, only structures and / or processing steps closely related to the solutions of the present application are shown in the drawings, and other details not closely related to the present application are omitted.

[0029] In addition, it should also be noted that the terms "comprise", "include" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or equipment including a series of elements not only includes those elements, but also includes other elements not explicitly listed or inherent to such a process, method, article or equipment.

[0030] The composite material with anticoagulant properties provided by the present application comprises:

[0031] A fabric;

[0032] At least two dip-coating layers formed on the surface of the fabric;

[0033] Two coating layers formed on the surface of the distal dip-coating layer of the fabric, and a microporous structure is formed on the side of the dip-coating layer close to the coating layer, at least a part of the coating layer is embedded in the microporous structure, and the pore size of the microporous structure is less than 5 μm.

[0034] The preparation method of the above-mentioned composite material comprises the following steps:

[0035] S1, immersing the fabric into a first polymer solution, taking it out after the solution infiltrates the fabric, drying, and obtaining a fabric with a dip-coating layer formed on the surface;

[0036] S2, immersing the fabric with the dip-coating layer obtained in step S1 into a MnO2-H3PO4-H2O ternary micro-etching system solution to etch the dip-coating layer and form a dip-coating layer with a microporous structure; after rinsing and drying, coating an amphoteric ion-containing second polymer solution on the surface of at least one dip-coating layer with a microporous structure, i.e. forming a coating layer on the surface of the dip-coating layer; after drying, the whole is subjected to catalytic reaction to obtain a composite material.

[0037] As an embodiment of the present application, in step S1, the mass fraction of the first polymer solution is 5-30%, and the solute of the first polymer solution includes but is not limited to one of polyether polyurethane (PEU), polyurethane urea (PEUU), polycarbonate polyurethane (PCU), polysiloxane polyurethane (PSU); and the solvent includes but is not limited to one of N,N-dimethylacetamide, toluene, tetrahydrofuran, acetone, dichloromethane.

[0038] As an embodiment of the present application, in step S1, the material of the fabric includes one or more of polyethylene terephthalate, polyethylene, polylactic acid, polypropylene, polyvinyl chloride, polytetrafluoroethylene.

[0039] As an embodiment of the present application, in step S1, the soaking time of the fabric in the first polymer solution is 60-400s. In this step, by adjusting the soaking times and soaking time of the fabric in the polymer solution, the thickness and uniformity of the dip-coating layer can be controlled. In some embodiments, the fabric can be soaked in the first polymer solution once, forming two dip-coating layers on the surface of the fabric, and the two dip-coating layers are located on both sides of the fabric. In other embodiments, multiple soaking can be used to form multiple dip-coating layers on the surface of the fabric.

[0040] As an embodiment of the present application, in step S2, the solute of the second polymer solution includes but is not limited to one of polyether urethane (PEU), polyurethane urea (PEUU), polycarbonate urethane (PCU), polysiloxane polyurethane (PSU); the solvent includes but is not limited to one of N,N-dimethylacetamide, toluene, tetrahydrofuran, acetone, dichloromethane. In order to improve the affinity between the dip-coating layer and the coating layer, in some embodiments, the composition of the dip-coating layer and the coating layer is the same.

[0041] As an embodiment of the present application, in step S2, the mass fraction of the second polymer solution is 5-30%, and the volume fraction of the zwitterionic is 3-30%. The specific preparation method is as follows: the zwitterionic monomer is dispersed in the second polymer solution to obtain the zwitterionic monomer, which includes but is not limited to one of 2-[(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA), carboxybetaine methacrylate (CBMA), 2-methacryloyloxyethylphosphocholine (MPC).

[0042] In addition to hydrogen bonding, the above-mentioned process of zwitterions can also form a hydration layer on the surface through electrostatic interaction, combining a large amount of water, thereby producing strong repulsive force on the protein, further inhibiting platelet adhesion; secondly, due to the difficulty of zwitterionic structure to enter the inside of protein molecules mainly with hydrophobic bond and hydrogen bond, it is beneficial to maintain the normal conformation of protein and reduce the activation of coagulation pathway.

[0043] As an embodiment of the present application, in step S2, the coating process includes but is not limited to one of brushing, rolling, wiping, and scraping.

[0044] As an embodiment of the present application, in step S2, when forming the coating layer, a second zwitterionic polymer solution can be first coated on the surface of the immersion coating layer with the microporous structure, and a coating layer is formed on one side of the fabric. After drying, another coating layer is formed on the other side of the fabric in the same way as described above. In other embodiments, a suitable process can be used to form the coating layer on both sides of the fabric at the same time.

[0045] As an embodiment of the present application, in step S2, the concentration of MnO2 in the MnO2-H3PO4-H2O ternary micro-etching system solution is 1-10 g / L, and the ratio of V(H3PO4) / V(H2O) is 1-5. The fabric is soaked in the ternary micro-etching system solution for 1-20 min at a temperature of 20-60℃. By the above method, the immersion coating layer can be chemically etched to form a microporous structure on the surface of the immersion coating layer, increase the surface roughness of the immersion coating layer, increase the specific surface area, promote mechanical engagement between the two, and improve the surface wettability of the fabric, effectively improving the adhesion of the immersion coating layer and the coating layer. Secondly, during the chemical etching process, the side chain of the first polymer can be opened, and oxygen free radicals can be formed on the surface of the immersion coating layer, which facilitates subsequent chemical crosslinking with the zwitterions in the coating layer, and improves the binding capacity between the zwitterions and the material.

[0046] As an embodiment of the present application, in step S2, the temperature of the catalytic reaction is 60-80℃, and the reaction time is 6-96h. The drying process is carried out at 30-50℃, and the drying time is 10min-30min, as long as the drying purpose can be achieved, which is not limited herein.

[0047] The present application provides a method for preparing a composite material with anticoagulant properties, which is prepared by sequentially preparing an immersion coating layer and a coating layer on the surface of a fabric substrate, and grafting zwitterions with anticoagulant function. In the above process, the fabric is used as a substrate, and the material properties such as softness, thickness, elasticity and mechanical strength can be adjusted by different weaving methods, so that it is more suitable as a biomedical material. A layer of immersion coating layer is formed on the surface of the fabric, which can effectively reduce the permeability of the fabric and improve its structural stability. A coating layer is further formed on the surface of the immersion coating layer, which can give the material a smooth surface, reduce its roughness, thereby reducing protein adsorption and platelet adhesion sites, and improving its blood compatibility. The double-layer structure of the immersion coating layer and the coating layer is more conducive to strengthening the structural stability of the material.

[0048] The application provides a preparation method of a composite material with an anticoagulant property, which comprises the following steps: forming a microporous structure on the surface of the dip-coating layer by chemical etching of the dip-coating layer, increasing the surface roughness of the dip-coating layer, improving the specific surface area, promoting mechanical engagement between the dip-coating layer and the coating layer, improving the surface wettability, and improving the bonding property between the dip-coating layer and the coating layer; in the process of chemical etching, the side chain of the polymer in the dip-coating layer is opened, and oxygen-containing free radicals are formed on the surface of the dip-coating layer; the oxygen-containing free radicals and the zwitterions in the coating layer are chemically crosslinked, the binding capacity between the zwitterions and the material is improved, and a long-term anticoagulation effect is achieved; and the zwitterions added in the coating layer can improve the anticoagulation effect by regulating the concentration of the zwitterions. In the above manner, the composite material with excellent mechanical property, good biocompatibility and long-term anticoagulant property is prepared.

[0049] The application provides a preparation method of a composite material with an anticoagulant property, which comprises the following steps: adding zwitterions with an anticoagulant property into a polymer solution for forming a coating layer, ensuring uniform distribution of the zwitterions in the composite material, and effectively improving the concentration of the zwitterions, so that the composite material has more excellent and stable anticoagulant property. The zwitterions are selected as the anticoagulant substance, and in addition to hydrogen bonds, the zwitterions can also form a hydration layer on the surface through electrostatic action and combine with a large amount of water, so that a strong repulsive force is generated on the protein, and the adhesion of platelets is further inhibited; in addition, the structure of the zwitterions is difficult to enter the inside of a protein molecule mainly in the form of hydrophobic bonds and hydrogen bonds, which is beneficial to maintaining the normal conformation of the protein and reducing the activation of the coagulation pathway, so that the composite material prepared in the application not only has excellent anticoagulant function, but also does not interfere with the physiological process, is not easy to cause postoperative complications, and has no problem of active decay.

[0050] In particular, the composite material prepared by the preparation method provided in the application can be applied to the field of biomedical materials, such as a high polymer leaf, a heart valve and the like.

[0051] The application provides a composite material with an anticoagulant property and a preparation method and application thereof, and the composite material is further limited in combination with the specific examples as follows: Embodiment

[0052] The embodiment prepares a composite material with an anticoagulant property, and the specific preparation method comprises the following steps:

[0053] S1, a fabric with a material of polyethylene is immersed into a polysiloxane polyurethane / N,N dimethylformamide solution with a concentration of 10% for 300s, and is dried at room temperature to obtain a fabric with a dip-coating layer formed on the surface;

[0054] S2, immerging the fabric with the immersion coating layer prepared in step S1 into a MnO2-H3PO4-H2O ternary micro-etching system solution, and reacting at 25℃ for 5 min to form a micro-porous structure on the surface of the immersion coating layer, wherein the concentration of MnO2 in the ternary micro-etching system solution is 5 g / L, and the ratio of V(H3PO4) / V(H2O) is 3; then, a polydimethylsiloxane polyurethane / N,N dimethylformamide solution containing 2-[(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl) ammonium hydroxide is coated on one side of the etched fabric by means of blade coating, i.e. a coating layer is formed on one side of the fabric; after drying at 40℃, the above steps are repeated to prepare another coating layer on the other side of the immersion coating layer, and after catalytic reaction, a composite material is prepared. The preparation steps of the polydimethylsiloxane polyurethane / N,N dimethylformamide solution containing 2-[(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl) ammonium hydroxide are as follows: first, a polydimethylsiloxane polyurethane / N,N dimethylformamide solution with a mass / volume fraction of 18% is prepared, and then 2-[(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl) ammonium hydroxide is added, with a volume fraction of 3% (i.e. 3 g of 2-[(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl) ammonium hydroxide is added to 100 mL of the polydimethylsiloxane polyurethane / N,N dimethylformamide solution), and the catalytic reaction is carried out at a temperature of 60℃ for 48 h. It should be noted that the raw materials and solutions used in the present application can be obtained by market purchase, unless otherwise specified.

[0055] The composite material prepared in the present example can be used as a polymer flap after being cut by a femtosecond laser, and the SEM image thereof is shown in FIG. 1. As can be seen from the figure, the surface of the composite material prepared in the present example is smooth. The SEM image of the micro-porous structure in step S2 is shown in FIG. 2. Example

[0056] A composite material with anticoagulant properties is prepared in the present example, and the specific preparation method comprises the following steps:

[0057] S1, immersing a fabric with a material of polyethylene into a polycarbonate polyurethane / tetrahydrofuran solution with a concentration of 8% for 200 s, and drying at room temperature to prepare a fabric with an immersion coating layer formed on the surface;

[0058] S2, the fabric with the immersion coating layer formed on the surface prepared in step S1 is immersed into a MnO2-H3PO4-H2O ternary micro-etching system solution, and is reacted at 60°C for 5 min to form a micro-porous structure on the surface of the immersion coating layer, wherein the concentration of MnO2 in the ternary micro-etching system solution is 3 g / L, and the V(H3PO4) / V(H2O) ratio is 2; then, a polyurethane / tetrahydrofuran solution containing methacryloyloxyethyl phosphocholine is coated on the surface of the etched fabric by using a rolling coating method, i.e. a coating layer is formed on the surface of the immersion coating layer; after drying at 40°C, the above steps are repeated to prepare another coating layer on the surface of another immersion coating layer, and the whole is subjected to a catalytic reaction to prepare a composite material. The preparation method of the polyurethane / tetrahydrofuran solution containing methacryloyloxyethyl phosphocholine is that a polyurethane solution with a mass / volume fraction of 20% is first prepared, and then methacryloyloxyethyl phosphocholine is added with a volume fraction of 15%; the catalytic reaction temperature is 70°C, and the reaction time is 36 h. Example

[0059] In this example, a composite material with anticoagulant properties is prepared, and the specific preparation method comprises the following steps:

[0060] S1, a fabric with a material of terephthalate glycol is immersed into a polysiloxane polyurethane / toluene solution with a concentration of 5% for 150 s, and is dried at room temperature to prepare a fabric with an immersion coating layer formed on the surface;

[0061] S2, the fabric with the immersion coating layer formed on the surface prepared in step S1 is immersed into a MnO2-H3PO4-H2O ternary micro-etching system solution, and is reacted at 60°C for 5 min to form a micro-porous structure on the surface of the immersion coating layer, wherein the concentration of MnO2 in the ternary micro-etching system solution is 3 g / L, and the V(H3PO4) / V(H2O) ratio is 2; then, a polyurethane / tetrahydrofuran solution containing methacryloyloxyethyl phosphocholine is coated on the surface of the etched fabric by using a rolling coating method, i.e. a coating layer is formed on the surface of the immersion coating layer; after drying at 40°C, the above steps are repeated to prepare another coating layer on the surface of another immersion coating layer, and the whole is subjected to a catalytic reaction to prepare a composite material. The preparation method of the polyurethane / tetrahydrofuran solution containing methacryloyloxyethyl phosphocholine is that a polyurethane solution with a mass / volume fraction of 20% is first prepared, and then methacryloyloxyethyl phosphocholine is added with a volume fraction of 15%; the catalytic reaction temperature is 70°C, and the reaction time is 36 h.

[0062] Comparative Example 1

[0063] The difference between Comparative Example 1 and Example 1 is only that the scraped polymer solution does not contain zwitterions, i.e., a polysiloxane polyurethane / N,N dimethylformamide solution with a mass volume concentration of 15% is used, and the rest of the experimental conditions are the same as those of Example 1, which will not be repeated here.

[0064] The surface water contact angle of the leaflet prepared in Comparative Example 1 is compared with that of Example 1, as shown in FIG. 3. As can be seen from the figure, the water contact angle of the leaflet prepared in Example 1 is 11.5±0.4°, and that of Comparative Example 1 is 97.4±0.9°. The results show that the hydrophilicity of the material can be significantly improved after modification of zwitterions. The surface anti-fibrinogen adsorption capacity of the leaflets of Example 1 and Comparative Example 1 is shown in FIG. 4. As can be seen from the figure, the absorbance value of the leaflet prepared in Example 1 is 0.76±0.05, and that of Comparative Example 1 is 2.33±0.24. The results show that the surface anti-fibrinogen adsorption capacity is significantly improved after modification of zwitterions. Among them, the water contact angle of the material surface is measured by a contact angle meter, and the anti-fibrinogen adsorption capacity of the material surface is measured by enzyme-linked immunosorbent assay (ELISA).

[0065] In addition, the platelet adhesion on the surface of the leaflet was also explored during the experiment. During the test, the leaflet was immersed in human platelet-rich plasma, incubated at 37°C for 1 h, then washed, fixed with 2.5% glutaraldehyde solution, dehydrated and dried, and the platelet adhesion on the surface of the material was observed by scanning electron microscopy, as shown in FIG. 5. As can be seen from the figure, the number of platelets adhered to the surface of the leaflet of Example 1 (FIG. 5a) is significantly less than that of Comparative Example 1 (FIG. 5b). An in vitro accelerated fatigue test was performed using a valve durability tester to make the valve work in a more rapid and more severe state than the actual one. The anti-coagulation effect of the leaflets prepared in Example 1 and Comparative Example 1 after a certain period of accelerated work was tested. The frequency of the test process was 15 Hz, and the cycle number was 150 million times. The results are shown in FIG. 6a and FIG. 6b. As can be seen from the figures, the platelet adhesion of the leaflet prepared in Example 1 (FIG. 6a) is significantly less than that of Comparative Example 1 (FIG. 6b) after a certain period of work, indicating that the long-term anti-coagulation effect of Example 1 is significantly stronger than that of Comparative Example 1.

[0066] Comparative Example 2

[0067] Comparative Example 2 differs from Example 1 only in that the surface micro-etching step is not performed, i.e. the second zwitterionic-containing polymer solution is coated directly onto the dip-coated layer of the fabric, and the remaining steps are the same as in Example 1, which are not repeated here. In-vitro accelerated fatigue testing was performed using a valve durability tester, which subjects the valve to a more rapid and more severe working condition than in reality, to test the anti-coagulation effect of the leaflets prepared in Example 1 and Comparative Example 2 after a certain period of accelerated working, and the results are shown in Figures 6a and 7, with a frequency of 15 Hz and a cycle number of 150 million times. It can be seen that the platelet adhesion of the leaflets prepared in Example 1 (Figure 6a) is significantly less than that of Comparative Example 2 (Figure 7) after a period of working, indicating that the long-term anti-coagulation effect of Example 1 is significantly stronger than that of Comparative Example 2. This is because: the micro-etching treatment in Example 1 forms a microporous structure on the surface of the dip-coated layer, and in the process of micro-etching, the side chains of the first polymer are opened and oxygen-containing free radicals are formed on the surface of the dip-coated layer, which chemically cross-link with the zwitterions in the coating layer, improving the binding ability between the zwitterions and the material. Therefore, after a period of working, the anti-coagulation effect of Example 1 still has a significant advantage.

[0068] The above examples are only used to illustrate the technical solutions of the present application and not to limit the present application. Although the present application has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present application can be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present application.

Claims

1. A method for producing a composite material having an anticoagulant property, characterized by, The method comprises the following steps: S1, immersing the fabric into a first polymer solution to obtain a fabric with at least two layers of dip-coating layers formed on the surface of the fabric; S2, immersing the fabric with the dip-coating layers obtained in step S1 into a MnO2-H3PO4-H2O ternary micro-etching system solution to etch the dip-coating layers and form dip-coating layers with micro-porous structures; Then, applying a second polymer solution containing zwitterions to the surface of at least one of the dip-coating layers with micro-porous structures to form a coating layer on the surface of the dip-coating layers; after drying, the whole is subjected to catalytic reaction to obtain a composite material.

2. The method for preparing the composite material with anticoagulant properties according to claim 1, characterized in that, In step S2, the second polymer solution containing zwitterions is prepared by dispersing zwitterionic monomers in a second polymer solution, the mass-volume fraction of the second polymer solution is 5-30%; the zwitterionic monomers are one or more of 2-[(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide, methacrylic acid carboxybetaine, and 2-methacryloyloxyethylphosphocholine, the volume fraction of which is 3-30%.

3. The method for preparing the composite material with anticoagulant properties according to claim 1, characterized in that, In step S2, the concentration of MnO2 in the MnO2-H3PO4-H2O ternary micro-etching system solution is 1-10 g / L, and the ratio of V(H3PO4) / V(H2O) is 1-5.

4. The method for preparing the composite material with anticoagulant properties according to claim 3, characterized in that, In step S2, the fabric is immersed in the ternary micro-etching system solution for 1-20 min at a temperature of 20-60℃; the catalytic reaction is carried out at a temperature of 60-80℃ for 6-96 h.

5. The method for preparing the composite material with anticoagulant properties according to claim 1, characterized in that, In step S1, the mass-volume fraction of the first polymer solution is 5-30%, the solute of the first polymer solution and / or the second polymer solution is a polyurethane polymer, the polyurethane polymer is one or more of polyether type polyurethane, polyurethane urea, polycarbonate type polyurethane, and polysiloxane polyurethane, and the solvent of the first polymer solution and / or the second polymer solution is one or more of N,N-dimethylacetamide, toluene, tetrahydrofuran, acetone, and dichloromethane.

6. The method for preparing the composite material with anticoagulant properties according to claim 1, characterized in that, In step S1, the fabric is made of one or more of polyethylene terephthalate, polyethylene, polylactic acid, polypropylene, polyvinyl chloride, and polytetrafluoroethylene; and the fabric is immersed in the first polymer solution for 60-400 s.

7. A composite material produced by the method of any one of claims 1 to 6, wherein The method comprises: a fabric; at least two layers of dip-coating layers formed on the surface of the fabric; two layers of coating layers formed on the surface of the distal dip-coating layer of the fabric, and a micro-porous structure is formed on the side of the dip-coating layer close to the coating layer, and at least a part of the coating layer is embedded in the micro-porous structure.

8. Use of the composite material prepared by the method of any one of claims 1-6 in the field of biomedical materials.

9. A prosthetic heart valve, comprising: The stent comprises a plurality of leaflets attached to the stent, and the leaflets comprise the composite material of claim 7.

10. The prosthetic heart valve of claim 9, wherein, The stent further comprises a skirt arranged on the stent, and the skirt comprises the composite material of claim 7.

Images