LONG-ACTING SUPERHYDROPHOBIC ANTICOAGULATION BIOLOGICAL VALVE AND PREPARATION METHOD THEREFOR

Abstract

A long-acting super-hydrophobic anticoagulant biological valve and a preparation method therefor. The preparation method includes the following steps: (1) treating a biological valve material with glutaraldehyde; (2) placing the biological valve material treated in step (1) into an acid liquid containing a polyphenol compound and metal ions, and adding an oxidant for reaction; and (3) reacting the biological valve material treated in step (2) with a hydrophobic substance. According to the method, a super-hydrophobic coating having a long-acting high water contact angle and a low rolling angle is prepared on the surface of the biological valve by means of a simple and stable operation process without affecting the performance of the valve body, and the requirements of long-acting anticoagulation are met by resisting the adsorption of plasma proteins.

Claims

1. A preparation method for a long-acting super-hydrophobic anticoagulant biological valve, comprising the following steps: (1) treating a biological valve material with glutaraldehyde; (2) placing the biological valve material treated in step (1) in an acid solution containing a polyphenol compound and metal ions, and adding an oxidant for reaction; and (3) reacting the biological valve material treated in step (2) with a hydrophobic substance.

2. The preparation method for the long-acting super-hydrophobic anticoagulant biological valve according to claim 1, wherein the treating with glutaraldehyde in step (1) includes immersing the biological valve material in a glutaraldehyde solution for 48 h to 96 h.

3. The preparation method for the long-acting super-hydrophobic anticoagulant biological valve according to claim 1, wherein in step (2), the oxidant has a concentration of 20 μM to 1 mM, and the reaction is performed at 10° C. to 40° C. for 20 min to 120 min.

4. The preparation method for the long-acting super-hydrophobic anticoagulant biological valve according to claim 1, wherein a molar mass ratio of the polyphenol compound and the metal ions is 1:0.01 to 1.

5. The preparation method for the long-acting super-hydrophobic anticoagulant biological valve according to claim 4, wherein the polyphenol compound is at least one of tannic acid, gallic acid, salvianolic acid B, epigallocatechin gallate, epicatechin gallate, epicatechin, epigallocatechin, catechol, pyrogallol, and flavonoid.

6. The preparation method for the long-acting super-hydrophobic anticoagulant biological valve according to claim 4, wherein the metal ions are at least one of copper ions, silver ions and iron ions.

7. The preparation method for the long-acting super-hydrophobic anticoagulant biological valve according to claim 1, wherein the acid solution has a pH value ranging from 4 to 6.

8. The preparation method for the long-acting super-hydrophobic anticoagulant biological valve according to claim 1, wherein the acid solution is acetic acid-acetate buffer, 2-(N-morpholine) ethanesulfonic acid buffer, glycine-hydrochloric acid buffer, phthalic acid-hydrochloric acid buffer, potassium hydrogen phthalate-sodium hydroxide buffer, disodium hydrogen phosphate-citric acid buffer or citric acid-sodium hydroxide-hydrochloric acid buffer.

9. The preparation method for the long-acting super-hydrophobic anticoagulant biological valve according to claim 1, wherein the oxidant is a water-soluble oxidant, which is, in particular, at least one of hydrogen peroxide, ammonium persulfate, cupric chloride, ferric chloride, concentrated nitric acid, sodium periodate, potassium permanganate and potassium dichromate.

10. The preparation method for the long-acting super-hydrophobic anticoagulant biological valve according to claim 1, wherein step (3) includes: immersing the biological valve material treated in step (2) in the hydrophobic substance with a concentration of 50 μM to 1 mM for 10 min to 30 min.

11. The preparation method for the long-acting super-hydrophobic anticoagulant biological valve according to claim 10, wherein the hydrophobic substance is perfluoropentadecane, perfluorododecanoic acid, 1H, 1H, 2H, 2H— perfluorododecanethiol, perfluorobutylethylene, stearoyl chloride or stearic acid.

12. The preparation method for the long-acting super-hydrophobic anticoagulant biological valve according to claim 1, wherein the biological valve material is an aortic valve, a pulmonary valve, a venous valve, a mitral valve or a tricuspid valve.

13. The preparation method for the long-acting super-hydrophobic anticoagulant biological valve according to claim 12, wherein the biological valve material is selected from porcine pericardium or bovine pericardium.

14. A long-acting super-hydrophobic anticoagulant biological valve, comprising a biological valve material, nanoparticles embedded in a surface of the biological valve material and formed by polymerization of a polyphenol compound and metal ions and containing double bond groups, and a hydrophobic coating formed by grafting a hydrophobic substance on surfaces of the nanoparticles.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0029] FIG. 1 is an SEM image of a biological valve super-hydrophobic fluoride coating prepared according to Example 1;

[0030] FIG. 2 shows the contact angle of the coating showing in FIG. 1;

[0031] FIG. 3 shows the platelet adhesion of a traditional glutaraldehyde valve in vitro;

[0032] FIG. 4 shows the platelet adhesion of a super-hydrophobic modified valve material prepared according to Example 2 of the present invention in vitro.

DESCRIPTION OF EMBODIMENTS

[0033] The specific embodiments of the present invention are described below so that those skilled in the art can understand the present invention, but it should be noted that the present invention is not limited to the scope of the specific embodiments. For those skilled in the art, various modifications within the spirit and scope of the present invention defined and determined by the appended claims are obvious, and all inventions using the concept of the present invention fall in the protection scope of the present invention.

EXAMPLE 1

[0034] A method for preparing a long-acting super-hydrophobic anticoagulant biological valve, includes the following steps: [0035] (1) Treat a porcine pericardial valve material cross-linked by glutaraldehyde; [0036] (2) Immerse the porcine pericardial valve material treated in step (1) in a buffer solution containing tannic acid and Cu.sup.2+ ions at a molar mass ratio of 1:0.1. The buffer solution is acetic acid-sodium acetate, and its pH value is 4. Then add an oxidant-sodium periodate with a concentration of 20 μM into the solution, and react at 25° C. for 40 minutes for an oxidative polymerization of the tannic acid and chelation with the Cu.sup.2+ ions at the same time, thereby forming polyphenol nanoparticles containing Cu.sup.2+ ions on the surface of the biological valve material; [0037] (3) Immerse the porcine pericardial valve material with polyphenol nanoparticles containing Cu.sup.2+ on the surface into 1H, 1H, 2H, 2H— perfluorododecanethiol with a molar concentration of 0.8 mM for 20 min, and then generate a uniform fluoride coating on the surface of the valve material by chemical grafting, thereby preparing a biological valve material with a super-hydrophobic coating on the surface.

EXAMPLE 2

[0038] A method for preparing a long-acting super-hydrophobic anticoagulant biological valve, includes the following steps: [0039] (1) Treat a porcine pericardial valve material cross-linked by glutaraldehyde; [0040] (2) Immerse the porcine pericardial valve material treated in step (1) in a buffer solution containing epigallocatechin gallate and Ag.sup.+ ions at a molar mass ratio of 1:0.05. The buffer solution is glycine-hydrochloric acid buffer solution, and its pH value is 4. Then add an oxidant-concentrated nitric acid with a concentration of 80 μM into the solution, and react at 25° C. for 60 minutes for an oxidative polymerization of the epigallocatechin gallate and chelation with the Ag.sup.+ ions at the same time, thereby forming polyphenol nanoparticles containing Ag.sup.+ ions on the surface of the biological valve material; [0041] (3) Immerse the porcine pericardial valve material with polyphenol nanoparticles containing Ag.sup.+ on the surface into perfluorododecanoic acid with a molar concentration of 0.5 mM for 25 min, and then generate a uniform fluoride coating on the surface of the valve material by chemical grafting, thereby preparing a biological valve material with a super-hydrophobic coating on the surface.

EXAMPLE 3

[0042] A method for preparing a long-acting super-hydrophobic anticoagulant biological valve, includes the following steps: [0043] (1) Treat a bovine pericardial valve material cross-linked by glutaraldehyde; [0044] (2) Immerse the bovine pericardial valve material treated in step (1) in a buffer solution containing epicatechin and Ag.sup.+ ions at a molar mass ratio of 1:0.2. The buffer solution is disodium hydrogen phosphate-citric acid, and its pH value is 4. Then add an oxidant-potassium permanganate with a concentration of 0.05 mM into the solution, and react at 20° C. for 40 minutes for an oxidative polymerization of the epicatechin and chelation with the Ag.sup.+ ions at the same time, thereby forming polyphenol nanoparticles containing Ag.sup.+ ions on the surface of the biological valve material; [0045] (3) Immerse the bovine pericardial valve material with polyphenol nanoparticles containing Ag.sup.+ on the surface into stearoyl chloride with a molar concentration of 0.2 mM for 10 min, and then generate a uniform super-hydrophobic coating on the surface of the valve material by chemical grafting, thereby preparing a biological valve material with a super-hydrophobic coating on the surface.

EXAMPLE 4

[0046] A method for preparing a long-acting super-hydrophobic anticoagulant biological valve, includes the following steps: [0047] (1) Treat a bovine pericardial valve material cross-linked by glutaraldehyde; [0048] (2) Immerse the bovine pericardial valve material treated in step (1) in a buffer solution containing pyrogallol and Fe.sup.3+ ions at a molar mass ratio of 1:0.05. The buffer solution is citric acid-sodium hydroxide-hydrochloric acid buffer solution, and its pH value is 4. Then add an oxidant-ammonium persulfate with a concentration of 0.01 mM into the solution, and react at 20° C. for 60 minutes for an oxidative polymerization of the pyrogallol and chelation with the Fe.sup.3+ ions at the same time, thereby forming polyphenol nanoparticles containing Fe.sup.3+ ions on the surface of the biological valve material; [0049] (3) Immerse the bovine pericardial valve material with polyphenol nanoparticles containing Fe.sup.3+ on the surface into stearic acid with a molar concentration of 0.05 mM for 30 min, and then generate a uniform fluoride coating on the surface of the valve material by chemical grafting, thereby preparing a biological valve material with a super-hydrophobic coating on the surface.

EXPERIMENTAL EXAMPLE

[0050] 1. The SEM image of the super-hydrophobic coating of the biological valve material prepared in Example 2 is shown in FIG. 1, and the test result of the contact angle is shown in FIG. 2.

[0051] As shown in FIGS. 1 and 2, the hydrophobic coating prepared by the present application is evenly distributed on the surface of the valve material, and has long-term high water contact angle and low rolling angle.

[0052] 2. Taking a glutaraldehyde valve as a control group and the biological valve material prepared in Example 2 as the experimental group, an in vitro platelet adhesion experiment was carried out to detect the anticoagulant performance, and the results are shown in FIG. 3 and FIG. 4.

[0053] As shown in FIG. 3 and FIG. 4, compared with the glutaraldehyde valve, the biological valve material prepared by the present application has excellent anticoagulant effect.