Polymer bionic coating and preparation method thereof

文档序号:1317710 发布日期:2020-07-14 浏览:23次 中文

阅读说明:本技术 一种聚合物仿生涂层及其制备方法 (Polymer bionic coating and preparation method thereof ) 是由 石强 项泽鸿 陈润海 马志方 王皓正 于 2020-03-19 设计创作,主要内容包括:本发明涉及医疗技术领域,尤其涉及一种聚合物仿生涂层及其制备方法。所述聚合物仿生涂层包括:衬底;附着在所述衬底上的内层,所述内层包括生物相容性聚合物和抗炎药物;附着在所述内层上的外层,所述外层包括炎症响应性聚合物。将由本发明的聚合物仿生涂层修饰的植介入医疗器械植介入血管的过程中,引起急性炎症,外层炎症响应性聚合物吸附过量的ROS,发生降解,消除急性炎症。外层降解后,露出内层,内层中含有抗炎症药物在血液环境中缓慢释放,实现抗慢性炎症的作用,提高植介入医疗器械安全性以及服役时间。本发明的聚合物仿生涂层具有抗血小板粘附的能力,具有较高的BCI指数,具有优异的抗凝血能力,可以有效抑制炎症和血栓的发生。(The invention relates to the technical field of medical treatment, in particular to a polymer bionic coating and a preparation method thereof. The polymer biomimetic coating comprises: a substrate; an inner layer attached to the substrate, the inner layer comprising a biocompatible polymer and an anti-inflammatory drug; an outer layer attached to the inner layer, the outer layer comprising an inflammation responsive polymer. When the polymer bionic coating modified plant interventional medical device is planted into an interventional blood vessel, acute inflammation is caused, and the outer inflammation responsive polymer adsorbs excessive ROS, is degraded and eliminates the acute inflammation. The outer layer is degraded to expose the inner layer, and the inner layer contains anti-inflammatory drugs which are slowly released in a blood environment, so that the effect of resisting chronic inflammation is realized, and the safety and the service time of the plant intervention medical instrument are improved. The polymer bionic coating has the capability of resisting platelet adhesion, has higher BCI index and excellent anticoagulation capability, and can effectively inhibit inflammation and thrombus.)

1. A polymeric biomimetic coating comprising:

a substrate;

an inner layer attached to the substrate, the inner layer comprising a biocompatible polymer and an anti-inflammatory drug;

an outer layer attached to the inner layer, the outer layer comprising an inflammation responsive polymer.

2. The polymer biomimetic coating according to claim 1, wherein the inflammation responsive polymer comprises one or more of phenylboronate polymers, aryl oxalate polymers, and alkyl thioether polymers;

the polymerization degree of the inflammation-responsive polymer is 2-2000;

the biocompatible polymer comprises one or more of polyethylene glycol polymer, polycaprolactone polymer, polyurethane polymer and heparin polymer.

3. The polymeric biomimetic coating according to claim 1, wherein the inflammation-responsive polymer comprises one or more of 4-methyl-1- (pinacol terephthalate) methoxy-2, 6-dimethanol, poly (butylene-1, 4-terephthalate-tetramethylene oxalate) copolymer, and polyethylene glycol diacrylate-ethylene glycol thiol copolymer;

the biocompatible polymer comprises one or more of heparin sodium, polyethylene glycol and polyvinylpyrrolidone;

the weight average molecular weight of the biocompatible polymer is 50000-130000 Da.

4. The polymeric biomimetic coating of claim 1, wherein the anti-inflammatory drug comprises one or more of an acetylsalicylate anti-inflammatory drug, a non-acetylsalicylate anti-inflammatory drug, and a non-salicylate anti-inflammatory drug.

5. The polymeric biomimetic coating of claim 1, wherein the anti-inflammatory drug comprises aspirin, acetaminophen, indomethacin, naproxen, diclofenac, ibuprofen, nimesulide, rofecoxib, or celecoxib.

6. The polymer biomimetic coating of claim 1, wherein the substrate comprises: a metal substrate composed of iron, magnesium, nickel, tungsten, titanium, zirconium, niobium, tantalum, zinc, or silicon; or a metal substrate composed of one or more of lithium, sodium, potassium, calcium, manganese, iron, and tungsten; or a ceramic substrate composed of zirconium dioxide and/or calcium hydroxy phosphate; or a polymer substrate composed of one or more of polyurethane polymers, polysulfone polymers, polyesters and polyether polymers.

7. The polymer biomimetic coating according to claim 1, wherein the mass fraction of the anti-inflammatory drug in the inner layer is 1-20%.

8. The polymer biomimetic coating according to claim 1, wherein the ratio of the thickness of the inner layer to the thickness of the outer layer is 0.5-3: 0.5 to 2.

9. A preparation method of a polymer bionic coating comprises the following steps:

A) uniformly attaching the inner layer mixed solution to the surface of the substrate by adopting an electrostatic spinning technology or an electrostatic spraying technology, and drying in vacuum to obtain an inner layer; the inner layer mixed solution comprises a biocompatible polymer, an anti-inflammatory drug and a first solvent;

B) uniformly attaching the outer-layer mixed solution to the surface of the inner layer by adopting an electrostatic spinning technology or an electrostatic spraying technology, and drying in vacuum to obtain a polymer bionic coating; the outer layer mixture includes an inflammation-responsive polymer and a second solvent.

10. The preparation method according to claim 9, wherein in step a), the first solvent is one or more selected from tetrahydrofuran, acetic acid, N-dimethylformamide, water and ethanol;

in the inner layer mixed solution, the mass concentration of the biocompatible polymer and the anti-inflammatory drug is 10-30%;

in the step B), the second solvent is one or more selected from dichloromethane, acetone, tetrahydrofuran, acetic acid, N-dimethylformamide, ethyl acetate, ethanol and chloroform;

in the outer layer mixed solution, the mass concentration of the inflammation responsive polymer is 3-15%.

Technical Field

The invention relates to the technical field of medical treatment, in particular to a polymer bionic coating and a preparation method thereof.

Background

Cardiovascular diseases have become the first cause of death in humans. Interventional medical devices such as cardiac stents, artificial blood vessels, heart valves and the like are implanted in cardiovascular systems, and are one of important means for cardiovascular treatment. Such medical devices are prone to thrombus formation on the medical device surface upon contact with blood, resulting in failure of the medical device. Through surface modification, thrombus caused by initial contact of blood and a medical device can be generally inhibited, but due to the fact that the interventional device is implanted in a blood environment for a long time, late and advanced thrombus can be caused by changes of the blood microenvironment, and the health of a patient is threatened. The formation of thrombi is closely related to the inflammatory response in the blood.

Two types of inflammation are usually caused by the implantation of the implant intervention material into the human body: 1) acute inflammation caused by surgical injury aggravates the degree of tissue injury, aggravates the pain of a patient and simultaneously causes thrombus in blood vessels; 2) Chronic inflammation caused by immune rejection of the implant, produced by the human autoimmune system. Such inflammation can lead to implant failure in the human body, and even to excessive proliferation of vascular Smooth Muscle Cells (SMC) in the case of blood contact, leading to a series of blood diseases such as deep vein thrombosis.

Currently, a common modification method for implanting interventional medical devices involves surface coating with drug-containing coatings, such as drug eluting cardiac stents (DES). Drug eluting stents will significantly reduce the probability of restenosis compared to bare metal stents. However, subsequent studies found that the rate of myocardial infarction and cardiovascular mortality increased inversely after implantation of such DES. This is mainly because: firstly, the drug coating is designed singly, and the coating is not designed according to the change of the blood microenvironment, so that the balance of the blood microenvironment can not be adjusted finally; secondly, the medicine is released, so that the surface structure of the coating is usually degraded, the blood compatibility of the instrument is deteriorated, and platelet aggregation and acute thrombosis are easily caused; finally, the coating design ignores the effect of inflammation on the device, which is a major cause of post-implantation and late thrombosis.

Disclosure of Invention

In view of the above, the technical problem to be solved by the present invention is to provide a polymer biomimetic coating and a preparation method thereof, and the polymer biomimetic coating provided by the present invention has excellent anti-inflammatory and anticoagulant effects, and improves the safety and service time of the plant intervention medical device.

The invention provides a polymer bionic coating, which comprises:

a substrate;

an inner layer attached to the substrate, the inner layer comprising a biocompatible polymer and an anti-inflammatory drug;

an outer layer attached to the inner layer, the outer layer comprising an inflammation responsive polymer.

Preferably, the inflammation-responsive polymer comprises one or more of phenylboronic acid ester polymers, aryl oxalate ester polymers and alkyl thioether polymers;

the polymerization degree of the inflammation-responsive polymer is 2-2000;

the biocompatible polymer comprises one or more of polyethylene glycol polymer, polycaprolactone polymer, polyurethane polymer and heparin polymer.

Preferably, the inflammation-responsive polymer comprises one or more of 4-methyl-1- (p-phenylboronic acid pinacol ester) methoxy-2, 6-dimethanol, poly (1, 4-butylene terephthalate-tetramethylene oxalate) copolymer and polyethylene glycol diacrylate-ethylene glycol dithiol copolymer;

the biocompatible polymer comprises one or more of heparin sodium, polyethylene glycol and polyvinylpyrrolidone;

the weight average molecular weight of the biocompatible polymer is 50000-130000 Da.

Preferably, the anti-inflammatory drug comprises one or more of acetylsalicylate anti-inflammatory drug, non-acetylsalicylate anti-inflammatory drug and non-salicylate anti-inflammatory drug.

Preferably, the anti-inflammatory drug comprises aspirin, acetaminophen, indomethacin, naproxen, naproxone, diclofenac, ibuprofen, nimesulide, rofecoxib, or celecoxib.

Preferably, the substrate includes: a metal substrate composed of iron, magnesium, nickel, tungsten, titanium, zirconium, niobium, tantalum, zinc, or silicon; or a metal substrate composed of one or more of lithium, sodium, potassium, calcium, manganese, iron, and tungsten; or a ceramic substrate composed of zirconium dioxide and/or calcium hydroxy phosphate; or a polymer substrate consisting of one or more of polyurethane polymers, polysulfone polymers, polyesters and polyether polymers.

Preferably, the mass fraction of the anti-inflammatory drug in the inner layer is 1-20%.

Preferably, the ratio of the thickness of the inner layer to the thickness of the outer layer is 0.5-3: 0.5 to 2.

The invention also provides a preparation method of the polymer bionic coating, which comprises the following steps:

A) uniformly attaching the inner layer mixed solution to the surface of a substrate by adopting an electrostatic spinning technology or an electrostatic spraying technology, and drying in vacuum to obtain an inner layer; the inner layer mixed solution comprises a biocompatible polymer, an anti-inflammatory drug and a first solvent;

B) uniformly attaching the outer-layer mixed solution to the surface of the inner layer by adopting an electrostatic spinning technology or an electrostatic spraying technology, and drying in vacuum to obtain a polymer bionic coating; the outer layer mixture includes an inflammation-responsive polymer and a second solvent.

Preferably, in the step a), the first solvent is one or more selected from tetrahydrofuran, acetic acid, N-dimethylformamide, water and ethanol;

in the inner layer mixed solution, the mass concentration of the biocompatible polymer and the anti-inflammatory drug is 10-30%;

in the step B), the second solvent is one or more selected from dichloromethane, acetone, tetrahydrofuran, acetic acid, N-dimethylformamide, ethyl acetate, ethanol and chloroform;

in the outer layer mixed solution, the mass concentration of the inflammation responsive polymer is 3-15%.

The invention provides a polymer bionic coating, which comprises: a substrate; an inner layer attached to the substrate, the inner layer comprising a biocompatible polymer and an anti-inflammatory drug; an outer layer attached to the inner layer, the outer layer comprising an inflammation responsive polymer. When the polymer bionic coating modified interventional medical device is implanted into an interventional blood vessel, the blood vessel is damaged and repaired to generate a large number of Reactive Oxygen Species (ROS), acute inflammation is caused, the coating shows self-adaptive behavior, and the outer-layer inflammation responsive polymer absorbs excessive ROS, is degraded and eliminates the acute inflammation. After the outer layer is degraded, the inner layer with high blood compatibility is exposed. The inner layer contains anti-inflammatory drugs which are slowly released in a blood environment, so that the effect of resisting chronic inflammation is realized, and the safety and the service time of the plant intervention medical device are improved. The invention embodies self-adaptability and intelligent responsiveness, reduces pathological reaction caused by implanting interventional medical instruments (such as vascular endoprostheses, intraluminal endoprostheses, stents, coronary stents or peripheral stents and the like), and prolongs the service life of the instruments.

Experiments show that the polymer bionic coating provided by the invention has the capability of resisting platelet adhesion, has a higher BCI index and excellent anticoagulation capability, and can effectively inhibit inflammation and thrombosis.

Drawings

FIG. 1 is a diagram of a process for preparing a polymer biomimetic coating according to an embodiment of the present invention;

FIG. 2 is an electron micrograph of a polymer biomimetic coating according to example 1 of the present invention;

FIG. 3 is an electron micrograph of the platelet adsorption of the polycaprolactone coating;

FIG. 4 shows BCI values of the polymer biomimetic coating and the aluminum foil of example 1 according to the present invention;

FIG. 5 shows the inflammatory factor TNF- α content of the polymeric biomimetic coating and bare substrate of example 1 of the present invention.

Detailed Description

The technical solutions of the present invention will be described clearly and completely with reference to the following embodiments of the present invention, and it should be understood that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. 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.

The invention provides a polymer bionic coating, which comprises:

a substrate;

an inner layer attached to the substrate, the inner layer comprising a biocompatible polymer and an anti-inflammatory drug;

an outer layer attached to the inner layer, the outer layer comprising an inflammation responsive polymer.

The polymer bionic coating provided by the invention comprises a substrate. In some embodiments of the invention, the substrate comprises: a metal substrate composed of iron, magnesium, nickel, tungsten, titanium, zirconium, niobium, tantalum, zinc, or silicon; or a metal substrate composed of one or more of lithium, sodium, potassium, calcium, manganese, iron, and tungsten; or a ceramic substrate consisting of one or more of zirconium dioxide, bioglass, alumina and calcium hydroxy phosphate; or a polymer substrate composed of one or more of polyurethane polymers, polysulfone polymers, polyesters and polyether polymers. The substrate is preferably a metal substrate composed of iron, magnesium, nickel, tungsten, titanium, zirconium, niobium, tantalum, zinc or silicon. In certain embodiments of the present invention, the metal substrate is a titanium alloy. In certain embodiments, the ceramic substrate is a bioglass ceramic (CaO-Na)2O-SiO2-P2O5) A sheet, an alumina bioceramic (VK-L05C) sheet, or a calcium hydroxy phosphate solid in certain embodiments of the invention, the polymer substrate is a polyurethane BASF membrane, a polysulfone P1700 membrane.

The polymeric biomimetic coating also includes an inner layer attached to the substrate. The inner layer includes a biocompatible polymer and an anti-inflammatory drug.

In certain embodiments of the present invention, the biocompatible polymer comprises one or more of a polyethylene glycol-based polymer, a polycaprolactone-based polymer, a polyurethane-based polymer, and a heparin-based polymer. In certain embodiments of the invention, the biocompatible polymer comprises one or more of heparin sodium, polyethylene glycol, and polyvinylpyrrolidone; the weight average molecular weight of the biocompatible polymer is 40000-130000 Da, preferably 50000-130000 Da. In certain embodiments of the invention, the biocompatible polymer has a weight average molecular weight of 40000Da, 50000Da, 60000Da, 70000Da, 80000Da, 86000Da, 100000Da, or 130000 Da.

In certain embodiments of the invention, the anti-inflammatory drug comprises one or more of an acetylsalicylate anti-inflammatory drug, a non-acetylsalicylate anti-inflammatory drug, and a non-salicylate anti-inflammatory drug. In certain embodiments of the invention, the anti-inflammatory drug comprises aspirin, acetaminophen, indomethacin, naproxen, naproxone, diclofenac, ibuprofen, nimesulide, rofecoxib, or celecoxib; preferably aspirin, indomethacin or naproxen.

In certain embodiments of the invention, the mass fraction of the anti-inflammatory drug in the inner layer is 1% to 30%; preferably 1 to 20 percent; more preferably 5% to 15%. In certain embodiments, the mass fraction of the anti-inflammatory drug in the inner layer is 15%, 5%, 6%, 9%, or 17%.

The polymeric biomimetic coating also includes an outer layer attached to the inner layer. The outer layer includes an inflammation responsive polymer. In certain embodiments of the present invention, the inflammation-responsive polymer comprises one or more of a phenylboronate-based polymer, an aryloxalate-based polymer, and an alkyl sulfide-based polymer; the polymerization degree of the inflammation-responsive polymer is 2-2000. In certain embodiments, the degree of polymerization of the inflammation-responsive polymer is 2 to 1000, 10 to 100, 2000, 1000, 2, 100, 10, or 20. In some embodiments, the phenylboronic acid ester polymer is 4-methyl-1- (p-phenylboronic acid pinacol ester) methoxy-2, 6-dimethanol, the aryl oxalate polymer is poly (1, 4-butylene terephthalate-tetramethylene oxalate) copolymer, and the alkyl sulfide polymer is one or more of polyethylene glycol diacrylate-ethylene glycol thiol copolymer.

In some embodiments of the present invention, the ratio of the thickness of the inner layer to the thickness of the outer layer is 0.5 to 4: 0.5 to 5. In certain embodiments, the ratio of the thickness of the inner layer to the thickness of the outer layer is 1: 1. 1.5: 1. 2: 1. 3: 1. 2: 0.7, 2: 1. 1: 2. 3: 2 or 4: 5. in certain embodiments, the outer layer has a thickness of 1500 μm, 1000 μm, 750 μm, 1400 μm, 600 μm, 500 μm, 200 μm, 70 μm, or 80 μm.

In the polymer bionic coating provided by the invention, the outer layer is a self-adaptive layer, and the purpose is that after the implant is implanted into a human body, the outer layer is used as an active ingredient to be rapidly degraded to adapt to environmental change, wherein the inflammation responsive polymer is released into body fluid, so that excessive Reactive Oxygen Species (ROS) caused by surgical injury can be efficiently eliminated, acute inflammation is treated, and the pain of a patient in the early stage after surgery is reduced. After the outer layer is degraded, the inner layer is exposed, and the inner layer is a biocompatible polymer and cannot cause cell damage. However, in order to avoid chronic inflammation caused by immunological rejection, the inner layer material contains anti-inflammatory drugs, preferably aspirin, indomethacin, naproxen. The anti-inflammatory drug is slowly released from the inner layer of the coating to achieve an anti-inflammatory effect.

The invention also provides a preparation method of the polymer bionic coating, which comprises the following steps:

A) uniformly attaching the inner layer mixed solution to the surface of a substrate by adopting an electrostatic spinning technology or an electrostatic spraying technology, and drying in vacuum to obtain an inner layer; the inner layer mixed solution comprises a biocompatible polymer, an anti-inflammatory drug and a first solvent;

B) uniformly attaching the outer-layer mixed solution to the surface of the inner layer by adopting an electrostatic spinning technology or an electrostatic spraying technology, and drying in vacuum to obtain a polymer bionic coating; the outer layer mixture includes an inflammation-responsive polymer and a second solvent.

In the preparation method of the polymer bionic coating provided by the invention, the adopted raw materials and components are the same as above, and are not described again.

Fig. 1 is a preparation process diagram of a polymer biomimetic coating provided by an embodiment of the present invention. Wherein, 1 is a substrate, 2 is an inner layer, 3 is an outer layer, and 4 is an electrostatic spinning device or an electrostatic spraying device.

The invention adopts the electrostatic spinning technology or the electrostatic spraying technology to uniformly adhere the mixed liquid of the inner layer on the surface of the substrate, and the inner layer is obtained after vacuum drying. The inner layer mixed solution includes a biocompatible polymer, an anti-inflammatory drug, and a first solvent.

In certain embodiments of the present invention, the first solvent is selected from one or more of tetrahydrofuran, acetic acid, N-dimethylformamide, water and ethanol.

In some embodiments of the invention, the mass concentration of the biocompatible polymer and the anti-inflammatory drug in the inner layer mixed solution is 10-30%; preferably 15 to 30 percent; more preferably 20% to 25%. In certain embodiments, the concentration by mass of the biocompatible polymer and the anti-inflammatory drug in the inner layer mixture is 12%, 31%, 21%, or 16%.

The method for preparing the inner layer mixed solution is not particularly limited, and a solution preparation method known to those skilled in the art may be used. In certain embodiments of the present invention, the inner layer mixture is prepared according to the following method:

the biocompatible polymer, the anti-inflammatory drug and the first solvent are mixed to obtain an inner layer mixed solution.

In certain embodiments of the present invention, the biocompatible polymer, the anti-inflammatory agent and the first solvent are mixed for 2 to 24 hours.

In the present invention, the spinning voltage or spraying voltage of the inner layer is preferably 10-30 kV, more preferably 15-25 kV, in the present invention 18kV, 19kV, 20kV, 21kV, 22 kV. in the present invention, the spinning speed or spraying injection speed of the inner layer is preferably 0.5-2 m L/h, particularly 0.5m L/h, 0.7m L/h, 0.8m L/h, 0.9m L/h, 1.0m L/h or 1.5m L/h in the present invention, the receiving distance of the receiver for spinning or spraying of the inner layer is preferably 10-20 cm, particularly 10cm, 12cm, 15cm, 18cm or 20 cm. in the present invention, the receiving time of the receiver for spinning or spraying of the inner layer is preferably 10 min-3 h, particularly 2h, 0.5h, 1h or 10min, 19G 17G in the present invention, or the electrostatic spraying process.

In some embodiments of the present invention, the temperature of the vacuum drying is 25 to 80 ℃. In certain embodiments, the temperature of the vacuum drying is 37 ℃. In certain embodiments of the present invention, the vacuum drying time is not less than 24 hours. In some embodiments, the vacuum drying time is 24-72 hours or 37 hours.

In the invention, the inner layer obtained by vacuum drying by adopting the electrostatic spinning technology is a fiber layer. In certain embodiments of the present invention, the fibers in the fiber layer have a diameter of 0.1 to 10 μm. In the invention, the inner layer obtained by adopting the electrostatic spraying technology and vacuum drying is a polymer particle layer. In some embodiments of the present invention, the polymer particles in the polymer particle layer have a diameter of 0.1 to 10 μm.

After the inner layer is obtained, uniformly attaching the outer layer mixed solution to the surface of the inner layer by adopting an electrostatic spinning technology or an electrostatic spraying technology, and drying in vacuum to obtain a polymer bionic coating; the outer layer mixture includes an inflammation-responsive polymer and a second solvent.

In certain embodiments of the present invention, the second solvent is selected from one or more of dichloromethane, acetone, tetrahydrofuran, acetic acid, N-dimethylformamide, ethyl acetate, ethanol, and chloroform.

In some embodiments of the invention, the mass concentration of the inflammation-responsive polymer in the outer layer mixture is 3-15%; preferably 6% to 10%. In certain embodiments, the mass concentration of the inflammation-responsive polymer in the outer layer mixture is 3%.

The preparation method of the outer layer mixed solution is not particularly limited in the present invention, and the solution preparation method known to those skilled in the art may be adopted. In certain embodiments of the present invention, the outer layer mixture is prepared according to the following method:

and mixing the inflammation-responsive polymer and the second solvent to obtain an outer-layer mixed solution.

In certain embodiments of the present invention, the time for mixing the inflammation-responsive polymer and the second solvent is 0.5 to 3 hours.

In the present invention, the spinning voltage or spraying voltage of the outer layer is preferably 5 to 15kV, more preferably 8 to 12kV, in the present invention example may be 7kV, 8kV, 9kV, 10kV, 11kV, 12 kV. the spinning speed or spraying injection speed of the outer layer is preferably 1 to 3m L/h, in the present invention example may be 1m L/h, 1.5m L/h, 2m L/h, 2.5m L/h, 2.8m L/h or 3m L/h, in the present invention, the receiving distance of the receiver of the spinning or spraying of the outer layer is preferably 15 to 30cm, in the present invention example may be 15cm, 20cm, 25cm, 28cm or 30 cm., in the present invention, the receiving time of the receiver of the spinning or spraying of the outer layer is preferably 0.01 to 2h, in the present invention may be 1.5h, 1h, 40min, 10min or 1min, in the present invention may be 15G, in the present invention example may be 15G, 17G, or 15G 17G in the present invention example may be used in the electrostatic spraying process.

In some embodiments of the present invention, the temperature of the vacuum drying is 25 to 80 ℃. In certain embodiments, the temperature of the vacuum drying is 37 ℃. In certain embodiments of the present invention, the vacuum drying time is not less than 24 hours. In some embodiments, the vacuum drying time is 24-72 hours, 37 hours or 48 hours.

In the present invention, the first solvent and the second solvent are mostly organic solvents, and the organic solvents are removed by the vacuum drying in order to eliminate the toxicity of the organic solvents. In certain embodiments of the invention, the vacuum drying is performed in a vacuum drying oven.

In the invention, the principle of the electrostatic spinning technology is basically the same as that of the electrostatic spraying technology, and the solution is attracted and attached to a designated receiver under the action of electrostatic force. In the process, the solvent of the solution is volatilized or partially volatilized, and the solute is precipitated and uniformly distributed on the surface of the receiver. Factors affecting the overall process include dc voltage, fluid injection rate, receiver distance, and needle diameter.

The source of the above-mentioned raw materials is not particularly limited in the present invention, and may be generally commercially available.

To further illustrate the present invention, a polymer biomimetic coating and method for making the same provided by the present invention are described in detail below with reference to examples, but they should not be construed as limiting the scope of the present invention.

The starting materials used in the following examples are all generally commercially available.

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