A functional biological heart valve material and its preparation method and use

Abstract

The present invention provides a functional biological heart valve material and a preparation method and use thereof, belonging to the field of biological heart valve materials. The present invention designs and synthesizes a novel non-glutaraldehyde valve crosslinker OX‑Br, introduces 4‑vinylphenylboronic acid and methacryloyloxyethyl phosphorylcholine into the porcine pericardium treated with OX‑Br through an in-situ polymerization reaction, and obtains a polymer brush block-modified heart valve material MP@OX‑PP. Further, anti-inflammatory drugs are introduced on the basis of MP@OX‑PP to obtain a functional biological heart valve material MPQ@OX‑PP. Compared with the glutaraldehyde-crosslinked biological heart valve material Glut‑PP, the heart valve material provided by the present invention has significantly improved anticoagulant performance, blood safety, anti-inflammatory effect and anti-calcification performance on the basis of maintaining similar mechanical properties and anti-enzymatic ability, and has broad application prospects in artificial biological valves with high comprehensive performance requirements.

Description

Technical Field

[0001] The present invention belongs to the field of biological heart valve materials, and in particular relates to a functional biological heart valve material and a preparation method and application thereof. Background Art

[0002] With the growth of population and the development of aging, more and more people are suffering from heart disease. Valvular heart disease, as a heart disease, threatens the lives of more than 100 million patients worldwide. However, due to the special physiological environment of heart valves, there is currently no specific drug for the treatment of valvular heart disease. Replacing heart valves with artificial heart valves is currently the best way to treat severe valvular heart disease. There are two types of artificial heart valves in clinical use: mechanical valves and biological heart valves (BHV). In recent years, with the development of minimally invasive interventional technology, transcatheter heart valve replacement (THVR), which has less trauma and faster recovery, has become the main solution for heart valve treatment. Compared with mechanical valves, BHV has superior hemodynamic properties, good anticoagulant properties and satisfactory compressibility, and has become the first choice for THVR. In recent years, the demand for BHV in clinical applications has been increasing.

[0003] Commercial artificial BHVs are usually made of porcine pericardium (PP) or bovine pericardium (BP) cross-linked with glutaraldehyde (Glut) to enhance the mechanical properties of the biomaterial and prevent degradation of the biomaterial after implantation. However, the fatal disadvantage of this type of BHV is its short lifespan, and the BHV after THVR can only be used for 10-15 years. Therefore, it is necessary to extend the service life of BHVs to serve a wider patient population. Studies have found that calcification is the primary problem that needs to be urgently solved for BHVs treated with glutaraldehyde. Calcification can harden the BHV, restrict its movement, and ultimately cause the BHV to fail to function normally and reduce its service life. At the same time, thrombosis is another reason why glutaraldehyde-treated BHVs have a short service life in clinical applications. In addition, the high toxicity of the residual aldehyde groups on the surface of the BHV treated with glutaraldehyde will also limit the adhesion and proliferation of endothelial cells, and the loss of the endothelial layer on the valve surface will further aggravate the formation of calcification and thrombosis.

[0004] In the past few decades, researchers have tried many ways to solve the problems of glutaraldehyde-treated artificial heart valves. Some non-glutaraldehyde compounds, such as epoxides, genipin, and carbodiimide, have been used to explore the possibility of cross-linking BHVs. However, most non-glutaraldehyde compounds cannot solve the basic problems of BHV mechanical properties and calcification, and non-glutaraldehyde cross-linked BHVs have not yet been further applied in clinical practice.

[0005] The literature (T.Yu et al; Nonglutaraldehyde treated porcine pericardium with good biocompatibility, reduced calcification and improved Anti-coagulation for bioprosthetic heart valve applications; Chemical Engineering Journal 414(2021)128900) reported a non-glutaraldehyde heart valve cross-linker: hydroxymethylbicyclic oxazolidine (OX-OH), and prepared an OX-OH cross-linked BHV (OX-OH-PP) using OX-OH and porcine pericardium as raw materials. Compared with BHV cross-linked with glutaraldehyde, OX-OH-PP not only maintains similar mechanical properties, but also exhibits better anti-calcification properties and biocompatibility. However, in order to meet clinical needs, the anti-inflammatory and anticoagulant properties of OX-OH-PP still need to be further optimized to expand its application in artificial bioprosthetic valves with high comprehensive performance requirements such as pulmonary valves and venous valves. Summary of the invention

[0006] The purpose of the present invention is to provide a novel non-glutaraldehyde valve crosslinking agent and a functional biological heart valve material prepared by using the non-glutaraldehyde valve crosslinking agent.

[0007] The present invention provides a biological valve material, which is a product obtained by atom transfer free radical polymerization of OX-Br cross-linked pericardium with 4-vinylphenylboronic acid and methacryloyloxyethyl phosphorylcholine; the structure of the OX-Br is as follows:

[0008]

[0009] Furthermore, the pericardium is decellularized pericardium, preferably decellularized porcine pericardium.

[0010] Furthermore, the OX-Br cross-linked pericardium is prepared by the following method: immersing the pericardium in an OX-Br solution, reacting at 35-40° C. for 3-7 days to obtain the OX-Br cross-linked pericardium; the mass concentration of the OX-Br solution is 3%-7%.

[0011] Furthermore, the reaction temperature is 37° C., the reaction time is 5 days, and the mass concentration of the OX-Br solution is 5%.

[0012] The present invention also provides a method for preparing the above-mentioned biological valve material, which comprises the following steps:

[0013] (1) immersing the OX-Br cross-linked pericardium in an organic solvent, removing oxygen, adding 4-vinylphenylboronic acid, a ligand and a catalyst, and performing an atom transfer radical polymerization reaction to obtain an intermediate product;

[0014] (2) Immersing the intermediate product in water to remove oxygen, adding methacryloyloxyethyl phosphorylcholine, a ligand and a catalyst to carry out an atom transfer radical polymerization reaction to obtain a biological valve material.

[0015] Furthermore, in step (1), the organic solvent is ethanol; the ligand is 1,1,4,7,10,10-hexamethyltriethylenetetramine; the catalyst is CuCl2 and CuCl, and the molar ratio of 4-vinylbenzeneboronic acid, 1,1,4,7,10,10-hexamethyltriethylenetetramine, CuCl2 and CuCl is 1:(5-20):(0.5-2):(2.5-10); the temperature of the atom transfer radical polymerization reaction is 20-30°C, and the time is 20-30 hours;

[0016] In step (2), the ligand is 1,1,4,7,10,10-hexamethyltriethylenetetramine, the catalyst is CuCl2 and CuCl, and the molar ratio of methacryloyloxyethyl phosphorylcholine, 1,1,4,7,10,10-hexamethyltriethylenetetramine, CuCl2 and CuCl is 1:(2.5-10):(0.25-1):(1.25-5); the temperature of the atom transfer radical polymerization reaction is 20-30°C and the time is 20-30 hours;

[0017] The molar ratio of 4-vinylbenzeneboronic acid to methacryloyloxyethyl phosphorylcholine is 1:(1-4).

[0018] Furthermore, in step (1), the molar ratio of 4-vinylbenzeneboronic acid, 1,1,4,7,10,10-hexamethyltriethylenetetramine, CuCl2 and CuCl is 1:10:1:5; the temperature of the atom transfer radical polymerization reaction is 25°C and the time is 24 hours;

[0019] In step (2), the molar ratio of the methacryloyloxyethyl phosphorylcholine, 1,1,4,7,10,10-hexamethyltriethylenetetramine, CuCl2 and CuCl is 1:5:0.5:2.5; the temperature of the atom transfer radical polymerization reaction is 25° C. and the time is 24 hours;

[0020] The molar ratio of the 4-vinylbenzeneboronic acid to methacryloyloxyethyl phosphorylcholine is 1:2.

[0021] The present invention also provides a functional biological valve material, which is a product obtained by the reaction of the above biological valve material and an anti-inflammatory drug; the anti-inflammatory drug is preferably quercetin.

[0022] The present invention also provides a method for preparing the above-mentioned functional biological valve material, which comprises the following steps: immersing the biological valve material in an anti-inflammatory drug solution, reacting, and obtaining a functional biological valve material; preferably, the concentration of the anti-inflammatory drug solution is 2 mg / mL, the reaction temperature is 25°C, and the reaction time is 24 hours.

[0023] The present invention also provides the use of the above-mentioned biological valve material and the above-mentioned functional biological valve material in the preparation of an artificial biological valve; the artificial biological valve is preferably an artificial heart valve, an artificial pulmonary valve or an artificial venous valve.

[0024] The invention designs and synthesizes a novel non-glutaraldehyde valve crosslinking agent OX-Br, which has both crosslinking ability and in-situ atom transfer radical polymerization (ATRP) function.

[0025] The present invention introduces 4-vinylphenylboronic acid (VBA) and methacryloyloxyethyl phosphorylcholine (MPC) into OX-Br treated porcine pericardium (OX-Br-PP) through in-situ polymerization to obtain a polymer brush block-modified heart valve material MP@OX-PP. Further, on the basis of MP@OX-PP, the anti-inflammatory drug quercetin is introduced to obtain a functional biological heart valve material MPQ@OX-PP.

[0026] The novel non-glutaraldehyde valve crosslinking agent of the present invention avoids the problem of residual aldehyde groups in the crosslinking process of the traditional glutaraldehyde crosslinking agent, and can fundamentally avoid the inherent risks of the glutaraldehyde crosslinking agent such as poor biocompatibility and easy calcification.

[0027] Compared with Glut-PP, a biological heart valve material cross-linked by glutaraldehyde, the heart valve material provided by the present invention has significantly improved anti-coagulation performance, blood safety, anti-inflammatory effect and anti-calcification performance while maintaining similar mechanical properties and anti-enzymatic ability. It has broad application prospects in the preparation of artificial biological valves with high comprehensive performance requirements such as heart valves, pulmonary valves, and venous valves.

[0028] Obviously, according to the above contents of the present invention, in accordance with common technical knowledge and customary means in the art, without departing from the above basic technical ideas of the present invention, other various forms of modification, replacement or change may be made.

[0029] The above contents of the present invention are further described in detail below through specific implementation methods in the form of embodiments. However, this should not be understood as the scope of the above subject matter of the present invention being limited to the following examples. All technologies realized based on the above contents of the present invention belong to the scope of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 .(A) Schematic diagram of the synthesis process of OX-Br; (B) 1 H NMR spectrum; (C) OX-Br 13 C NMR spectrum, * represents CDCl3.

[0031] Figure 2 .HRMS spectrum of OX-Br.

[0032] Figure 3 .Schematic diagram of the synthesis of MPQ@OX-PP.

[0033] Figure 4 (A) SEM images of Glut-PP, OX-Br-PP, MP@OX-PP and MPQ@OX-PP after platelet adhesion experiment; (B) Quantitative results of platelet adhesion of Glut-PP, OX-Br-PP, MP@OX-PP and MPQ@OX-PP; (C) and (E) Quantitative results of thrombus and sample performance of Glut-PP, OX-Br-PP, MP@OX-PP and MPQ@OX-PP in whole blood coagulation experiment; (D) and (F) Hemolysis results and sample performance (+ represents positive control group, - represents negative group). *** indicates P < 0.001, n = 6.

[0034] Figure 5 .(A) Schematic diagram of the in vitro blood circulation experiment; (B) Intraoperative photograph of establishing in vitro blood circulation; (C) Photographs before and after the Glut-PP, OX-Br-PP, MP@OX-PP and MPQ@OX-PP experiments; (D) Scanning electron microscope images after the Glut-PP, OX-Br-PP, MP@OX-PP and MPQ@OX-PP experiments. Figure 6(A) DAPI (blue) and FITC-phalloidin (green) staining of RAW 246.7 cells cultured with extracts of control group, control group (+LPS), Glut-PP (+LPS), OX-Br-PP (+LPS), MP@OX-PP (+LPS), and MPQ@OX-PP (+LPS), scale bar 200 μm; TNF-α (B), IL-6 (C), and TGF-β1 (D) concentrations of control group, control group (+LPS), Glut-PP (+LPS), OX-Br-PP (+LPS), MP@OX-PP (+LPS), and MPQ@OX-PP (+LPS). *** indicates P < 0.001, n = 6.

[0035] Figure 7 (A) Alizarin red stained sections of Glut-PP, OX-Br-PP, MP@OX-PP and MPQ@OX-PP after 30 and 60 days of implantation; (B) and (C) Quantitative analysis of calcification of Glut-PP, OX-Br-PP, MP@OX-PP and MPQ@OX-PP at 30 and 60 days. *** indicates P < 0.001 compared with Glut-PP; n = 6. DETAILED DESCRIPTION

[0036] Unless otherwise specified, the raw materials and equipment used in the present invention are all known products, which are obtained by purchasing commercially available products.

[0037] Unless otherwise specified, the temperature of the operating steps in the examples is room temperature (i.e. 25±5°C).

[0038] Unless otherwise specified, the solutions described in the examples are aqueous solutions.

[0039] OX-OH was prepared according to the method described in the literature (T. Yu et al; Nonglutaraldehyde treated porcinepericardium with good biocompatibility, reduced calcification and improved Anti-coagulation for bioprosthetic heart valve applications; Chemical Engineering Journal 414 (2021) 128900).

[0040]

[0041] Example 1: Preparation of non-glutaraldehyde valve crosslinker OX-Br

[0042]

[0043] according to Figure 1 The route shown in A is to synthesize OX-Br. The specific operation is as follows:

[0044] OX-OH (20.00 g, 0.14 mol) and triethylamine (18.14 g, 0.18 mol) were placed in a flask and dissolved with 200 mL of tetrahydrofuran. Then, α-bromoisobutyryl bromide was diluted with 150 mL of tetrahydrofuran and dropped into the flask. After reacting for 24 hours, the mixed solution was centrifuged for 20 minutes, and the supernatant was concentrated with a rotary evaporator. Then, it was recrystallized with ethyl acetate / n-hexane (wherein the volume ratio of ethyl acetate to n-hexane was 1:20) at -20°C to obtain purified OX-Br (29.36 g, yield 72.41%).

[0045] The structures of the obtained OX-Br are respectively 1 H NMR, 13 The results were verified by C NMR and high resolution mass spectrometry (HRMS). Figure 1 and Figure 2 shown.

[0046] Example 2: Preparation of a functional biological heart valve

[0047] according to Figure 3 The specific steps are as follows:

[0048] 1. Preparation of Heart Valve OX-Br-PP

[0049] Fresh porcine pericardium was collected and washed with deionized water at 4°C and 100rpm for 2 hours; then, the animal biological tissue was decellularized with a mixture of 0.1wt% sodium dodecyl sulfate and 0.1wt% deoxycholic acid for 3 hours to obtain decellularized porcine pericardium (D-PP). The decellularized porcine pericardium was prepared into a size of 110mm×110mm, immersed in a 5% mass concentration OX-Br solution, reacted at 37°C for 5 days, and then taken out and washed with deionized water to obtain the heart valve OX-Br-PP.

[0050] 2. Preparation of MP@OX-PP Heart Valve

[0051] OX-Br-PP was placed in a reaction vessel containing 30 mL of ethanol, and oxygen was removed by ultrasound and argon flushing. Then, 4-vinylbenzeneboronic acid (VBA, 3.00 g, 0.02 mol), 1,1,4,7,10,10-hexamethyltriethylenetetramine (0.046 g, 0.2 mmol), CuCl2 (0.0025 g, 0.02 mmol) and CuCl (0.0099 g, 0.1 mmol) were added to the vessel for atom transfer radical polymerization (ATRP) reaction. After reacting at 25°C for 24 hours, the reacted sample was washed with ethanol and deionized water to remove unreacted reactants. Next, the sample was placed in 300 mL of deionized water, and oxygen was removed by ultrasound and argon flushing. Then, methacryloyloxyethyl phosphorylcholine (MPC, 12.00 g, 0.04 mol), 1,1,4,7,10,10-hexamethyltriethylenetetramine (0.046 g, 0.2 mmol), CuCl2 (0.0025 g, 0.02 mmol) and CuCl (0.0099 g, 0.1 mmol) were added to carry out ATRP reaction. After reacting at 25°C for 24 hours, the mixture was washed with 1 mg / ml sodium ethylenediaminetetraacetic acid (NaEDTA) solution and deionized water to obtain heart valve MP@OX-PP.

[0052] 3. Preparation of MPQ@OX-PP Heart Valve

[0053] The MP@OX-PP was immersed in a 2 mg / mL quercetin solution, reacted at 25°C for 24 hours, and then washed with deionized water to obtain the heart valve MPQ@OX-PP.

[0054] The following is the preparation method of the control sample Glut-PP.

[0055] Comparative Example 1: Preparation of Glut-PP

[0056] Prepare a 1.5% glutaraldehyde solution (w / v), add 6% NaCl (w / v) to it, and adjust the pH to 5 with 1M hydrochloric acid. Then place the fixed decellularized porcine pericardium (D-PP) vertically in the glutaraldehyde solution and shake at room temperature for 2 hours to allow the glutaraldehyde solution to penetrate into the porcine pericardium as much as possible. Finally, slowly adjust the pH to neutral with a saturated sodium carbonate solution, shake at room temperature at 120 rpm for 24 hours for cross-linking, take out and ultrasonically clean 5 times to obtain a glutaraldehyde-cross-linked biological heart valve: Glut-PP.

[0057] The beneficial effects of the present invention are demonstrated by experimental examples below.

[0058] Experimental Example 1: Anti-thrombotic adhesion and hemolysis experiments

[0059] 1. Experimental methods

[0060] Fresh rabbit blood was collected in a vacuum blood collection tube, centrifuged at 1000 rpm for 10 min, and the precipitate was diluted 10 times with PBS. n=6) were soaked in PBS overnight and placed in a 48-well plate. Then, 200μL of diluent and 800μL of PBS were added to each well and incubated at 37℃ for 2h. The positive control group (+) was H2O and the negative control group (-) was PBS. After incubation, the solution was mixed evenly with the red blood cell sediment on the surface of the sample and transferred to a 2mL centrifuge tube. After centrifugation at 3000rpm for 10min, photos were taken to observe whether there was obvious hemolysis. In addition, 200μL of supernatant was taken and the absorbance value at 541nm was measured. The hemolysis rate of each group of samples was calculated using the absorbance value.

[0061] Glut-PP, OX-Br-PP, MP@OX-PP, MPQ@OX-PP ( n=6) were washed 3 times with PBS and placed in a 96-well plate. Fresh rabbit blood (200μL) was added to CaCl2 solution (100mM, 4μL) and quickly added to the sample well. After incubation in a 37℃ incubator for 15 minutes, the clotted samples were carefully removed and gently washed in PBS solution until the PBS was colorless and transferred to a new 96-well plate. Finally, 300μL of 0.5% triton solution was added to each sample well and incubated at 37℃ for 1h. After the thrombus on the sample surface was completely dissolved, it was diluted 4 times with PBS solution and the absorbance was measured at 405nm with an enzyme reader to quantify the thrombus on the sample surface.

[0062] 2. Experimental results

[0063] The experimental results are as follows Figure 4 As shown, it can be seen that compared with the glutaraldehyde-crosslinked biological heart valve Glut-PP, the MP@OX-PP and MPQ@OX-PP of the present invention have significantly improved anti-platelet adhesion effects (4A, 4B), the MP@OX-PP and MPQ@OX-PP of the present invention have significantly improved anti-thrombotic adhesion effects (4C, 4E), and the MP@OX-PP and MPQ@OX-PP of the present invention have excellent blood safety and will not produce hemolysis.

[0064] Experimental Example 2: Blood Safety Experiment

[0065] 1. Experimental methods

[0066] Samples from different groups were cut into rectangles of 15mm×10mm in size. After sterilization, the samples were repeatedly washed with sterile PBS, and all subsequent operations were performed under sterile conditions. The sterilized samples were placed in PVC tubes and assembled into pipelines that could be connected to arteries and veins. The New Zealand white rabbits were then anesthetized with sodium pentobarbital solution, their neck arteries and veins were separated, and they were connected to the pipelines after puncture to establish a circulation loop. After circulating for 1 hour, the pipeline was removed and the samples were washed three times with saline. After the samples were weighed, they were fixed with 2.5% glutaraldehyde solution. After dehydration, critical point drying, gold spraying, and SEM were used to observe the surface of the samples.

[0067] 2. Experimental results

[0068] The experimental results are as follows Figure 5 As shown, it can be seen that compared with the glutaraldehyde cross-linked biological heart valve Glut-PP, the MP@OX-PP and MPQ@OX-PP of the present invention have significantly improved blood safety. In addition, compared with MP@OX-PP, the blood safety of MPQ@OX-PP is better.

[0069] Experimental Example 3: Anti-inflammatory Function Experiment

[0070] 1. Experimental methods

[0071] Glut-PP, OX-Br-PP, MP@OX-PP, and MPQ@OX-PP were sterilized and the extracts were prepared using 1640 complete medium containing 1 mM hydrogen peroxide. RAW246.7 cells were seeded on glass-bottomed culture dishes using RPMI 1640 complete medium at 2 × 10 cells per well. 4 4×10 cells per well of a 48-well plate 4 cells. After 24 hours of co-culture, 1 mL of 10 μg / mL LPS solution was added to activate RAW 246.7 cells for 2 hours. After the activation of RAW 246.7 was completed, the extracts of each group were added to the culture dish or well plate and cultured for another 24 hours. RAW 246.7 cells on the glass bottom plate were fixed with 2.5% glutaraldehyde, and the cell morphology was stained with FITC-Phalloidin and DAPI solution. The cell supernatant of each group of samples was collected in a 48-well plate, and the levels of IL-6, TNF-α and TGF-β1 in each group were detected according to the instructions of the corresponding ELISA kit.

[0072] 2. Experimental results

[0073] The experimental results are as follows Figure 6As shown, it can be seen that the MPQ@OX-PP of the present invention can prevent macrophages from being activated, downregulate proinflammatory factors TNF-α and IL-6, and upregulate anti-inflammatory factor TGF-β1. Compared with the glutaraldehyde-crosslinked biological heart valve Glut-PP, the MPQ@OX-PP of the present invention has significantly improved anti-inflammatory function.

[0074] Experimental Example 4: Anti-calcification ability experiment

[0075] 1. Experimental methods

[0076] The samples were cut into 1cm×1cm size (n=6x 3) and washed three times with PBS. Then, they were sterilized by soaking in 75% ethanol solution for 12h. After sterilization, they were washed three times with PBS, each time for 15min, to ensure that the residual ethanol was completely removed. Male SD rats were selected as implantation objects, weighing about 50g, and the experiment was carried out after being raised for one week. After the rats were anesthetized by intraperitoneal injection of 10% chloral hydrate, two 1cm incisions were made on both sides of the rats' backs and expanded to the outside to form two pockets that were not connected to each other. The samples were placed in the two pockets, and the membranes were kept flat during implantation. After implantation, the wounds were sutured with sutures, and the wounds were wiped with iodine to prevent bacterial infection. The materials were taken out at 30 days and 60 days, respectively, for quantitative analysis of calcification.

[0077] 2. Experimental results

[0078] The experimental results are as follows Figure 7 As shown, it can be seen that compared with the glutaraldehyde-crosslinked biological heart valve Glut-PP, the MP@OX-PP and MPQ@OX-PP of the present invention have significantly improved anti-calcification ability.

Claims

1. A biological valve material, characterized in that: It is the product obtained by atom transfer radical polymerization of OX-Br cross-linked pericardium with 4-vinylphenylboronic acid and methacryloyloxyethyl phosphorylcholine; the structure of OX-Br is shown below:

2. The bioprosthetic valve material according to claim 1, characterized in that: The pericardium is pericardium after decellularization.

3. The bioprosthetic valve material according to claim 2, characterized in that: The decellularized pericardium is decellularized porcine pericardium.

4. The bioprosthetic valve material according to any one of claims 1 to 3, characterized in that: The OX-Br cross-linked pericardium is prepared by the following method: immersing the pericardium in an OX-Br solution and reacting at 35-40° C. for 3-7 days to obtain the OX-Br cross-linked pericardium; the mass concentration of the OX-Br solution is 3%-7%.

5. The bioprosthetic valve material according to claim 4, characterized in that: The reaction temperature is 37° C., the reaction time is 5 days, and the mass concentration of the OX-Br solution is 5%.

6. A method for preparing the bioprosthetic valve material according to any one of claims 1 to 5, characterized in that: It includes the following steps: (1) immersing the OX-Br cross-linked pericardium in an organic solvent, removing oxygen, adding 4-vinylphenylboronic acid, a ligand and a catalyst, and performing an atom transfer radical polymerization reaction to obtain an intermediate product; (2) Immersing the intermediate product in water to remove oxygen, adding methacryloyloxyethyl phosphorylcholine, a ligand and a catalyst to carry out an atom transfer radical polymerization reaction to obtain a biological valve material.

7. The method according to claim 6, characterized in that: In step (1), the organic solvent is ethanol; the ligand is 1,1,4,7,10,10-hexamethyltriethylenetetramine; the catalyst is CuCl2 and CuCl, and the molar ratio of 4-vinylbenzeneboronic acid, 1,1,4,7,10,10-hexamethyltriethylenetetramine, CuCl2 and CuCl is 1:(5-20):(0.5-2):(2.5-10); the temperature of the atom transfer radical polymerization reaction is 20-30°C and the time is 20-30 hours; In step (2), the ligand is 1,1,4,7,10,10-hexamethyltriethylenetetramine, the catalyst is CuCl2 and CuCl, and the molar ratio of methacryloyloxyethyl phosphorylcholine, 1,1,4,7,10,10-hexamethyltriethylenetetramine, CuCl2 and CuCl is 1:(2.5-10):(0.25-1):(1.25-5); the temperature of the atom transfer radical polymerization reaction is 20-30°C and the time is 20-30 hours; The molar ratio of 4-vinylbenzeneboronic acid to methacryloyloxyethyl phosphorylcholine is 1:(1-4).

8. The method according to claim 7, characterized in that: In step (1), the molar ratio of 4-vinylbenzeneboronic acid, 1,1,4,7,10,10-hexamethyltriethylenetetramine, CuCl2 and CuCl is 1:10:1:5; the temperature of the atom transfer radical polymerization reaction is 25° C. and the time is 24 hours; In step (2), the molar ratio of the methacryloyloxyethyl phosphorylcholine, 1,1,4,7,10,10-hexamethyltriethylenetetramine, CuCl2 and CuCl is 1:5:0.5:2.5; the temperature of the atom transfer radical polymerization reaction is 25° C. and the time is 24 hours; The molar ratio of the 4-vinylbenzeneboronic acid to methacryloyloxyethyl phosphorylcholine is 1:

2.

9. A functional biological valve material, characterized in that: It is a product obtained by the reaction of the biological valve material described in any one of claims 1 to 5 and an anti-inflammatory drug.

10. The functional bioprosthetic valve material according to claim 9, characterized in that: The anti-inflammatory drug is quercetin.

11. A method for preparing the functional biological valve material according to claim 9, characterized in that: It includes the following steps: The biological valve material is immersed in an anti-inflammatory drug solution to react and obtain a functional biological valve material.

12. The method according to claim 11, characterized in that: The concentration of the anti-inflammatory drug solution is 2 mg / mL, the reaction temperature is 25° C., and the reaction time is 24 hours.

13. Use of the biological valve material according to any one of claims 1 to 5 and the functional biological valve material according to claim 9 in the preparation of artificial biological valves.

14. The use according to claim 13, characterized in that: The artificial bio-valve is an artificial heart valve, an artificial pulmonary valve or an artificial venous valve.

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