阅读说明：本技术 生物医用材料及其制备方法 (Biomedical material and preparation method thereof ) 是由 李小丽 陈昌盛 储彬 王松 刘伟强 于 2020-06-12 设计创作，主要内容包括：一种生物医用材料的制备方法,其包括以下步骤提供基底；将所述基底置于包括生物配体的第一溶液中,所述生物配体包括盐酸多巴胺和多酚化合物中的至少一种,所述生物配体能够发生自聚合反应,从而在所述基底的表面形成聚多巴胺链接层；在所述聚多巴胺链接层上形成亲水润滑涂层,从而得到所述生物医用材料。本发明还提供一种生物医用材料。本发明的制备方法过程简单易行,有利于规模化生产,在生物医用材料表面形成亲水润滑且牢固的涂层,亲水润滑性显著,能有效改善生物医用材料的表面性能。(A method for preparing biomedical materials comprises providing a substrate; placing the substrate in a first solution comprising a biological ligand, the biological ligand comprising at least one of dopamine hydrochloride and a polyphenol compound, the biological ligand being capable of undergoing a self-polymerization reaction, thereby forming a polydopamine linker layer on the surface of the substrate; forming a hydrophilic lubricating coating on the polydopamine linking layer, thereby obtaining the biomedical material. The invention also provides a biomedical material. The preparation method disclosed by the invention is simple and feasible in process, is beneficial to large-scale production, forms a hydrophilic lubricating and firm coating on the surface of the biomedical material, is remarkable in hydrophilic lubricating property, and can effectively improve the surface performance of the biomedical material.)

1. A preparation method of a biomedical material is characterized by comprising the following steps:

providing a substrate;

placing the substrate in a first solution comprising a biological ligand, the biological ligand comprising at least one of dopamine hydrochloride and a polyphenol compound, the biological ligand being capable of undergoing a self-polymerization reaction, thereby forming a polydopamine linker layer on the surface of the substrate;

forming a hydrophilic lubricating coating on the polydopamine linking layer, thereby obtaining the biomedical material.

2. The method of claim 1, wherein the first solution further comprises a buffer solution, the buffer solution comprises one or more of tris buffer solution, morpholino sulfonic acid buffer solution, and N-2-hydroxyethylpiperazine-N-3-propanesulfonic acid buffer solution, and the pH of the first solution is 8.0 to 8.9.

3. The method of preparing a biomedical material according to claim 1, wherein the polyphenol compound comprises at least one of a flavonoid, catechol, flavanone, anthocyanidin, catechol, and pyrogallol.

4. The method of preparing a biomedical material according to claim 1, wherein the concentration of said bioligand in said first solution is from 0.01mg/mL to 20 mg/mL.

5. The method of claim 1, wherein the self-polymerization reaction is performed in a shaker at a temperature of 25 ℃ to 60 ℃, for a time of 20h to 28h, and at a rotation speed of 5rpm to 100 rpm.

6. The method of preparing a biomedical material according to claim 1, wherein the preparation of said hydrophilic lubricious coating comprises the steps of:

applying a second solution on the polydopamine linker layer, the second solution comprising a hydrophilic polymer and a photoinitiator; and

and (3) carrying out illumination curing on the second solution, so that the hydrophilic polymer is crosslinked and cured under the action of the photoinitiator, thereby forming the hydrophilic lubricating coating.

7. The method of claim 6, wherein the hydrophilic polymer comprises a first hydrophilic polymer, and the first hydrophilic polymer comprises one or more of hyaluronic acid methacrylate and derivatives thereof, chitosan methacrylate and derivatives thereof, collagen methacrylate, sodium alginate methacrylate and derivatives thereof, gelatin methacrylate and derivatives thereof, chondroitin sulfate methacrylate and derivatives thereof, chitosan methacrylate and derivatives thereof, polyvinyl alcohol, polyethylene glycol methacrylate and derivatives thereof, polyvinylpyrrolidone, and polyvinyl ether.

8. The method of claim 7, wherein the hydrophilic polymer further comprises a second hydrophilic polymer, and the second hydrophilic polymer comprises one or more of poly-2-acrylamide-2-methylpropanesulfonic acid, poly-2-hydroxyethyl methacrylate, hyaluronic acid and derivatives thereof, chitosan and derivatives thereof, xanthan gum, agarose, sodium alginate, gelatin, chondroitin sulfate, chitose, polyvinyl alcohol, polyethylene glycol and derivatives thereof, polyvinylpyrrolidone, and polyvinyl ether.

9. The method of claim 8, wherein the mass ratio of the first hydrophilic polymer to the second hydrophilic polymer is 0.1 to 2, and the concentrations of the first hydrophilic polymer and the second hydrophilic polymer in the second solution are both 1mg/mL to 200 mg/mL.

10. The method of claim 1, wherein the substrate comprises one of stainless steel, cobalt-based alloys, titanium and its alloys, magnesium and its alloys, pure iron, polyethylene, polyvinyl chloride, polytetrafluoroethylene, polypropylene, polymethyl methacrylate, medical polysulfone, medical polysiloxane, polyether sulfone membrane, polyurethane, and natural rubber.

11. A biomedical material produced by the process for producing a biomedical material according to any one of claims 1 to 10, comprising a substrate, a polydopamine linking layer for linking the substrate and the hydrophilic lubricating coating, and a hydrophilic lubricating coating.

Technical Field

The invention relates to the technical field of biomedical materials, in particular to a biomedical material and a preparation method thereof.

Background

The surface of the interventional medical device is directly contacted with the human body, so that friction is generated between the surface of the interventional medical device and the tissue, the tissue is damaged, and the pain of a patient is increased. Through surface modification of medical instruments, the hydrophilicity and lubricity of the surface are increased, so that the friction force can be obviously reduced, the discomfort of a patient is effectively relieved, and complications caused by damage of mucosa and tissue cells in the insertion process are avoided. The hydrophilic polymer is the simplest surface modification technology for coating the surface of the medical appliance, but the hydrophilic coating is weak in firmness and easy to fall off.

Disclosure of Invention

In order to solve the technical problems, the invention provides a method for preparing a biomedical material, which has hydrophilicity, low friction force, firmness and difficult falling.

In addition, the method comprises the following steps. The invention also provides a biomedical material.

The invention provides a preparation method of a biomedical material, which comprises the following steps:

providing a substrate;

placing the substrate in a first solution comprising a biological ligand, the biological ligand comprising at least one of dopamine hydrochloride and a polyphenol compound, the biological ligand being capable of undergoing a self-polymerization reaction, thereby forming a polydopamine linker layer on the surface of the substrate;

forming a hydrophilic lubricating coating on the polydopamine linking layer, thereby obtaining the biomedical material.

Further, the first solution also comprises a buffer solution, the buffer solution comprises one or more of a trihydroxymethyl aminomethane buffer solution, a morpholinosulfonic acid buffer solution and an N-2-hydroxyethylpiperazine-N-3-propanesulfonic acid buffer solution, and the pH value of the first solution is 8.0-8.9.

Further, the polyphenol compound includes at least one of flavonoid, catechol, flavanone, anthocyanin, catechol, and pyrogallol.

Further, the concentration of the biological ligand in the first solution is 0.01 mg/mL-20 mg/mL.

Further, the self-polymerization reaction is carried out in a shaking table, the temperature of the self-polymerization reaction is 25-60 ℃, the time of the self-polymerization reaction is 20-28 h, and the rotating speed of the shaking table is 5-100 rpm.

Further, the preparation of the hydrophilic lubricating coating comprises the following steps:

applying a second solution on the polydopamine linker layer, the second solution comprising a hydrophilic polymer and a photoinitiator; and

and (3) carrying out illumination curing on the second solution, so that the hydrophilic polymer is crosslinked and cured under the action of the photoinitiator, thereby forming the hydrophilic lubricating coating.

Further, the hydrophilic polymer comprises a first hydrophilic polymer, and the first hydrophilic polymer comprises one or more of methacrylic acid hyaluronic acid and derivatives thereof, methacrylic acid chitosan and derivatives thereof, methacrylic acid collagen, methacrylic acid sodium alginate and derivatives thereof, methacrylic acid gelatin and derivatives thereof, methacrylic acid chondroitin sulfate and derivatives thereof, methacrylic acid chitose and derivatives thereof, polyvinyl alcohol, methacrylic acid polyethylene glycol and derivatives thereof, polyvinylpyrrolidone and polyvinyl ether.

Further, the hydrophilic polymer also comprises a second hydrophilic polymer, and the second hydrophilic polymer comprises one or more of poly-2-acrylamide-2-methylpropanesulfonic acid, poly-2-hydroxyethyl methacrylate, hyaluronic acid and derivatives thereof, chitosan and derivatives thereof, xanthan gum, agarose, sodium alginate, gelatin, chondroitin sulfate, chitose, polyvinyl alcohol, polyethylene glycol and derivatives thereof, polyvinylpyrrolidone and polyvinyl ether.

Further, the mass ratio of the first hydrophilic polymer to the second hydrophilic polymer is 0.1-2, and the concentrations of the first hydrophilic polymer and the second hydrophilic polymer in the second solution are both 1-200 mg/mL.

Further, the substrate comprises one of stainless steel, cobalt-based alloy, titanium and its alloy, magnesium and its alloy, pure iron, polyethylene, polyvinyl chloride, polytetrafluoroethylene, polypropylene, polymethyl methacrylate, medical polysulfone, medical polysiloxane, polyether sulfone film, polyurethane and natural rubber.

The invention also provides the biomedical material prepared by the preparation method of the biomedical material, which comprises a substrate, a polydopamine linking layer and a hydrophilic lubricating coating, wherein the polydopamine linking layer is used for linking the substrate and the hydrophilic lubricating coating.

Compared with the prior art, the invention has the beneficial effects that: according to the invention, a polydopamine linking layer is formed on the surface of the substrate material through oxidative autopolymerization deposition of the biological ligand, so that the substrate material and the hydrophilic lubricating coating material can be firmly linked, and a hydrophilic lubricating coating with good firmness is formed on the surface of the biomedical material. Since the biological ligand is oxidized and self-polymerized in a weak alkaline environment and can form a polydopamine linkage layer on the surface of different substrates, the method is suitable for modifying the surface of most biological materials. The method has the advantages of simple and easy process, contribution to large-scale production, remarkable hydrophilic lubricity and capability of effectively improving the surface performance of the biomedical material.

Detailed Description

The technical solution of the present invention will be clearly and completely described below with reference to specific embodiments. It is to be understood that the described embodiments are merely exemplary of the invention, and not restrictive of the full scope of the invention. All other embodiments, which can be obtained by a person skilled in the art without any inventive step based on the embodiments of the present invention, are within the scope of the present invention.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The names of technical means used in the description of the present invention are for the purpose of describing specific embodiments only, and are not intended to limit the present invention.

The embodiments described below and the features of the embodiments can be combined with each other without conflict.

The invention provides a preparation method of a biomedical material, which comprises the following steps:

step S1, providing a substrate, and pre-treating the substrate material.

The substrate material comprises one of stainless steel, cobalt-based alloy, titanium and alloy thereof, magnesium and alloy thereof, pure iron, polyethylene, polyvinyl chloride, polytetrafluoroethylene, polypropylene, polymethyl methacrylate, medical polysulfone, medical polysiloxane, polyether sulfone membrane, polyurethane and natural rubber.

And (3) carrying out ultrasonic cleaning on the different materials, removing dust, dirt, an oxide layer and the like on the surface of the substrate material, and carrying out vacuum drying after cleaning for later use. The specific cleaning method can be realized by selecting the prior art capable of achieving the pretreatment purpose according to different materials.

Step S2, forming a polydopamine linkage layer on the surface of the substrate.

Placing the substrate pretreated in step S1 in a first mixed solution including a buffer solution and a biological ligand, wherein the biological ligand includes at least one of dopamine hydrochloride and polyphenol compound, and the biological ligand is capable of undergoing a self-polymerization reaction in a weak alkaline environment in the presence of the buffer solution, so as to deposit and form a polydopamine-linked layer on the surface of the substrate.

In this embodiment, the buffer solution comprises one or more of Tris-HCl buffer solution (Tris-HCl), morpholinosulfonic acid buffer solution (MES), and N-2-hydroxyethylpiperazine-N-3-propanesulfonic acid (HEPPS) buffer solution. Since the pH value has a great influence on the thickness, firmness and polymer morphology of the formed polydopamine linkage layer, in the present embodiment, when the pH value is 8.0 to 8.9, the biological ligand can form a firmer polydopamine linkage layer in this range, preferably, the pH value is 8.3 to 8.7, more preferably, the pH value is 8.5 to 8.6, and when the pH value is 8.5 to 8.6, the formed polydopamine linkage layer is firmer.

In this embodiment, the polyphenolic compound comprises a mixture of one or more of flavonoids, catechols, flavanones, anthocyanins, catechol, and pyrogallol.

In this embodiment, the concentration of the bioligand in the first solution is 0.01mg/mL to 20 mg/mL.

In this embodiment, the self-polymerization reaction is performed in a shaking table, the temperature of the self-polymerization reaction is 25 ℃ to 60 ℃, the time of the self-polymerization reaction is 20h to 28h, and the rotation speed of the shaking table is 5rpm to 100 rpm.

According to the invention, biological ligands can generate oxidation self-polymerization deposition in a weak alkaline environment in the presence of the buffer solution, a polydopamine linking layer is formed on the surface of the substrate, and the polydopamine linking layer can firmly link a substrate material and a hydrophilic lubricating coating material of a surface layer. Moreover, since the biological ligand is subjected to oxidative self-polymerization in a weak alkaline environment and the polydopamine linkage layer can be formed on different substrate surfaces, the method is suitable for modification of the surfaces of most biological materials. In this embodiment, the dopamine hydrochloride can undergo oxidative autopolymerization deposition to form polydopamine, and the polyphenol compound can also undergo oxidative autopolymerization deposition to form a polydopamine structure. Research finds that Polydopamine (PDA) has super-strong adhesion performance, PDA can be rapidly deposited to form a film on the surfaces of various materials under an alkaline condition, and the film contains a large number of hydrophilic hydroxyl and amino functional groups, so that the hydrophilicity and chemical versatility of the surfaces of the materials can be effectively improved. And the formation process of the PDA is simple, an organic solvent is not needed, and the PDA can promote the adhesion of cells, has good biocompatibility and is more suitable for the modification of the surface of a biological material.

Step S3, drying of the polydopamine coating.

And cleaning the substrate material with the polydopamine linkage layer formed on the surface for 6-10 times by using deionized water, wherein the cleaning time is 1-6 min each time, and then drying the substrate material under a vacuum condition, wherein the drying temperature is 40-60 ℃.

Step S4, forming a hydrophilic lubricating coating on the polydopamine linking layer, thereby obtaining the biomedical material, specifically including the steps of:

applying a second solution on the polydopamine linker layer, the second solution comprising a hydrophilic polymer and a photoinitiator; and

and (3) carrying out illumination curing on the second solution, so that the hydrophilic polymer is crosslinked and cured under the action of the photoinitiator, thereby forming the hydrophilic lubricating coating.

In this embodiment, the hydrophilic polymer includes a first hydrophilic polymer and/or a second hydrophilic polymer, and the first hydrophilic polymer is a hydrophilic polymer containing a photo-curing functional group, and includes one or more of methacrylic acid hyaluronic acid and its derivatives, methacrylic acid chitosan and its derivatives, methacrylic acid collagen, methacrylic acid sodium alginate and its derivatives, methacrylic acid gelatin and its derivatives, methacrylic acid chondroitin sulfate and its derivatives, methacrylic acid chitose and its derivatives, polyvinyl alcohol (PVA), methacrylic acid polyethylene glycol (PEG) and its derivatives, polyvinylpyrrolidone (PVP), and polyvinyl ether. The concentration of the first hydrophilic polymer in the second solution is 1 mg/mL-200 mg/mL.

The second hydrophilic polymer comprises one or more of poly-2-acrylamide-2-methylpropanesulfonic acid, poly-2-hydroxyethyl methacrylate, hyaluronic acid and derivatives thereof, chitosan and derivatives thereof, xanthan gum, agarose, sodium alginate, gelatin, chondroitin sulfate, chitose, polyvinyl alcohol, polyethylene glycol and derivatives thereof, polyvinylpyrrolidone and polyvinyl ether. The concentration of the second hydrophilic polymer in the second solution is 1 mg/mL-200 mg/mL.

In the present embodiment, when the first hydrophilic polymer and the second hydrophilic polymer are added simultaneously, the mass ratio of the first hydrophilic polymer to the second hydrophilic polymer is 0.1 to 2.

In this embodiment, the photoinitiator is 2-hydroxy-4' (2-hydroxyethoxy) -2-methyl propiophenone (Irgacure 2959).

In this embodiment, the solvent includes one or more of water, ethanol, isopropanol, acetone, ethyl acetate, acetic acid, and N, N-dimethylformamide.

In this embodiment, the second solution is cured by Ultraviolet (UV) irradiation for a period of time, so that the poly-dopamine linkage layer and the hydrophilic lubricating coating material are cross-linked and cured, and hydrophilic lubricating functional molecules are attached to the surface of the poly-dopamine linkage layer, thereby forming a hydrophilic lubricating coating.

According to the invention, the poly-dopamine linkage layer is added on the surface of the substrate, so that a network bonding structure can be formed with the hydrophilic lubricating material, and the hydrophilic lubricating material is combined with the substrate more firmly, thereby improving the surface hydrophilic lubricating property of the biomedical material and improving the firmness of the hydrophilic lubricating coating on the surface of the biomedical material.

The invention is further illustrated by the following examples.