CN113786518A - Preparation method of composite coating for surface modification of medical material - Google Patents
Preparation method of composite coating for surface modification of medical material Download PDFInfo
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- 239000011248 coating agent Substances 0.000 title claims abstract description 94
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- 239000012567 medical material Substances 0.000 title claims abstract description 36
- 230000004048 modification Effects 0.000 title claims abstract description 31
- 238000012986 modification Methods 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims abstract description 29
- 239000012224 working solution Substances 0.000 claims abstract description 68
- 239000000463 material Substances 0.000 claims abstract description 64
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- 238000000034 method Methods 0.000 claims abstract description 29
- 102000009027 Albumins Human genes 0.000 claims abstract description 24
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- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 3
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- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
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- HLXZNVUGXRDIFK-UHFFFAOYSA-N nickel titanium Chemical compound [Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni] HLXZNVUGXRDIFK-UHFFFAOYSA-N 0.000 description 1
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Images
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/08—Materials for coatings
- A61L31/10—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/0005—Use of materials characterised by their function or physical properties
- A61L33/0011—Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/23—Carbohydrates
- A61L2300/236—Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/42—Anti-thrombotic agents, anticoagulants, anti-platelet agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/606—Coatings
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- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Surgery (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Materials Engineering (AREA)
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Abstract
The invention discloses a preparation method of a composite coating for surface modification of a medical material, which comprises the following steps: s1, polishing the surface of the medical substrate material, sequentially putting the medical substrate material into acetone and absolute ethyl alcohol for ultrasonic cleaning, then taking out the medical substrate material after plasma treatment, putting the medical substrate material into a grafting agent solution for soaking for 2-6 hours, finally cleaning with deionized water and drying in vacuum to obtain the surface-modified medical substrate material; s2, preparing coating working solution, wherein the coating working solution comprises heparin sodium working solution with required concentration, albumin working solution and coupling agent working solution; s3, generating a coating on the medical substrate material by a low-speed flow circulation method. The preparation method of the composite coating has simple and convenient process steps and short production time, and can obviously improve the production efficiency; by controlling the circulating speed, the circulating sequence of the working solution and the selection of the working solution, the thickness of the generated coating is easier to control, the generated coating has better uniformity, and the performance of the heparin-albumin composite coating is improved.
Description
Technical Field
The invention belongs to the technical field of preparation of surface coatings of medical materials, and particularly relates to a preparation method of a composite coating for surface modification of a medical material.
Background
Anticoagulant biomedical materials are important biomaterials and widely applied to medical materials which are in contact with human blood and tissues, such as hemodialysis systems, extracorporeal circulation systems, artificial heart valves, cardiac pacemakers, artificial blood vessels, vascular stents and the like. The application of biomedical materials faces two major problems, biocompatibility and hemocompatibility. The coating technology is to coat the surface of the material with a substance to perform a pre-modification treatment so as to improve the performance of the material. Heparin coating technology is currently the most widely used coating technology.
Heparin belongs to mucopolysaccharide, and can act with various blood coagulation inhibiting factors such as antithrombin III to enhance the activity of the heparin so as to achieve the aim of anticoagulation. The surface of the artificial material is coated with heparin, so that the blood compatibility and the biocompatibility of the material can be effectively improved. The biomedical material surface coating principle can be divided into a chemical grafting method and a physical coating method. The material is heparinized by a physical method, the heparin is easy to run off, and the anticoagulation effect is not long; the material is heparinized by a chemical method, and after heparin is biological macromolecules and is covalently bonded on the surface of a metal material, the conformation of the heparin is limited, so that the anticoagulant activity is reduced. In addition, coating polymers used to immobilize heparin also have biocompatibility problems and do not promote endothelial healing.
Chinese patent CN 102695530A discloses a novel heparin entity and its application method, which comprises bonding heparin and another component such as protein, polysaccharide, polymer, etc. into heparin entity through coupling reaction, and oxidizing the heparin entity to generate heparin entity containing aldehyde group; finally, the polyethyleneimine is fixed on the medical substrate by using a coupling agent, and the aldehyde heparin entity is grafted on the polyethyleneimine of the medical substrate by the steps of Schiff base-reductive amination and the like.
When the heparin entity is used for surface coating of medical materials, the following differences are provided: 1) the process steps are complicated, and the production time is long; 2) when the aldehyde heparin entity is grafted on the polyethyleneimine of the medical substrate, the thickness and the uniformity of the coating are difficult to control, and the performance of the generated medical material is influenced; 3) the production cost is expensive. Therefore, there is a need for improvement of the existing process for forming heparin composite coating on the surface of medical material.
Disclosure of Invention
The invention aims to provide a preparation method of a composite coating for surface modification of a medical material, which can solve the problems that the existing production process of a heparin composite coating on the surface of the medical material in the background art is complicated in steps, long in consumed time, difficult to control the thickness and uniformity of the coating, high in price and the like.
In order to achieve the purpose, the invention is realized by the following technical scheme: a preparation method of a composite coating for surface modification of medical materials is characterized by comprising the following steps: which comprises the following steps:
s1, polishing the surface of the medical substrate material, sequentially putting the medical substrate material into acetone and absolute ethyl alcohol for ultrasonic cleaning, treating the polished and cleaned medical substrate material with plasma, taking out the medical substrate material, putting the medical substrate material into a grafting agent solution for soaking for 2-6 h, finally cleaning with deionized water and drying in vacuum to obtain the surface-modified medical substrate material;
s2, preparing coating working solution, wherein the coating working solution comprises heparin sodium working solution with required concentration, albumin working solution and coupling agent working solution;
s3, generating a coating on the medical substrate material by a low-speed flow circulation method, which comprises the steps of depositing heparin and albumin on the medical substrate material by the coating working solution configured in the step S2 in a low-speed flow circulation mode, carrying out chemical grafting by a coupling agent, and enabling the heparin-albumin composite coating to be stably combined with the medical substrate material to generate the coating, wherein in the coating preparation process, each parameter of the low-speed flow circulation, namely the circulation sequence, the circulation frequency, the flow speed or the circulation time of each working solution, is regulated and controlled, so that the thickness of the generated coating is controlled.
As a further improvement of the preparation method of the composite coating for surface modification of the medical material, the medical substrate material is one of stainless steel, titanium alloy, cobalt-based alloy and nickel-titanium shape memory alloy.
As a further improvement of the above preparation method of the composite coating for surface modification of a medical material, the plasma treatment method of the medical substrate material described in step S1 includes: vacuum at 3X 10 of background-2 ～5×10-2Using N under the conditions of Pa and power of 300-400W2Or Ar gas plasma is used for treating the surface of the medical substrate material for 8-20 min. The surface of the medical substrate material is treated by plasma by setting the vacuum pressure and power, so that the surface of the substrate material is more favorable for generating a heparin-albumin coating.
As a further improvement of the above preparation method for the composite coating for surface modification of medical materials, in step S1, the grafting agent is selected from one or a mixture of several of dopamine, acrylic acid, acrylamide and polyethylene glycol. By selecting the grafting agent, after the heparin and the albumin are deposited on the surface of the medical substrate material, the connection between the heparin and the albumin and the medical substrate material is firmer.
As a further improvement of the preparation method of the composite coating for surface modification of the medical material, the concentration of the heparin sodium working solution is 0.10-1.0 g/L, and the pH value is 2.0-5.0.
As a further improvement of the preparation method of the composite coating for surface modification of the medical material, the concentration of the albumin working solution is 0.10-1.0 g/L, and the pH value is 2.0-5.0.
As a further improvement of the preparation method of the composite coating for surface modification of the medical material, the working solution of the coupling agent is 1- (3-dimethylaminopropyl) -3-Ethylcarbodiimide (EDC) or a saturated calcium chloride solution, the concentration is 0.10-1.0 g/L, and the pH is 2.0-5.0.
By selecting and setting the concentration and pH value of the heparin sodium working solution, the albumin working solution and the coupling agent working solution, the uniformity of the generated heparin-albumin coating is better, the thickness is easier to control, and the performance of the generated coating is better.
As a further improvement of the above method for preparing a composite coating for surface modification of a medical material, the method for circulating each working fluid in the low-speed flow circulation method described in step S3 includes: before the first circulation, the circulation pipeline is firstly washed by deionized water, then the albumin working solution is used for circulation in sequence, then the deionized water is used for washing, then the heparin sodium working solution is used for circulation, and then the deionized water is used for washing, when the second circulation is carried out, the albumin working solution is used for circulation, then the deionized water is used for washing, then the heparin sodium working solution is used for circulation, the repeated circulation is carried out for 3-5 times, and finally the coupling agent working solution is used for circulation, so that the heparin-albumin composite coating with the required thickness is generated. By controlling the circulation sequence and the circulation speed of the low-speed flow circulation system, the generation process of the heparin-albumin coating can be strictly controlled, so that the generation thickness of the heparin-albumin coating is controlled, and the uniformity of the coating is improved.
As a further improvement of the preparation method of the composite coating for surface modification of the medical material, in step S3, the circulation time of the albumin working solution, the heparin sodium working solution and the cross-linking agent working solution is 5-60 min, and the flow rates of the three working solutions are 1-2L/h.
As a further improvement of the preparation method of the composite coating for surface modification of the medical material, the thickness of the generated heparin-albumin composite coating is controlled to be 1-500 mu m. The thickness of the heparin-albumin composite coating can be set and generated according to the requirements of medical materials.
The invention has the beneficial effects that: 1) the preparation method of the composite coating for surface modification of the medical material comprises the following steps of firstly, polishing a medical substrate material, carrying out plasma treatment, soaking a grafting agent, washing with deionized water, carrying out vacuum drying and the like, so that the subsequent deposition of albumin and heparin is smoother; 2) the preparation method of the composite coating for surface modification of the medical material has the advantages of simple and convenient process steps, short production time and capability of obviously improving the production efficiency; 3) the preparation method of the composite coating for surface modification of the medical material generates the heparin-albumin composite coating on the surface of the medical substrate material in a low-speed flow circulation mode, and the generation process of the heparin-albumin coating is easy to control by controlling the circulation speed, the circulation sequence of the working solution and the selection of the working solution, so that the thickness of the generated coating is easier to control, the generated coating has better uniformity, and the performance of the heparin-albumin composite coating is improved.
Drawings
Fig. 1 is a data chart of a water contact angle test before and after the composite coating is prepared by the preparation method of the present invention on the medical base material in the test 1.
Fig. 2 is a graph of data from test 2 for heparin content and durability tests on composite coatings of the present invention.
Detailed Description
The technical solutions of the present invention are described clearly and completely by the following embodiments, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
A preparation method of a composite coating for surface modification of medical materials comprises the following steps:
s1, polishing the surface of a medical substrate material, wherein the medical substrate material can be stainless steel, titanium alloy, cobalt-based alloy, nickel-titanium shape memory alloy and other materials, polishing to enable the surface of the medical substrate material to be flat and uniform without obvious pits and bulges, then sequentially placing the medical substrate material into acetone and absolute ethyl alcohol for ultrasonic cleaning for 3min, then placing the medical substrate material into deionized water for ultrasonic cleaning for 4 min, and then placing the medical substrate material into an oven for drying; then go to medicinePlasma treatment with the substrate material in a background vacuum of 3X 10-2Processing the surface of the medical metal sheet by using Ar gas plasma for 10min under the conditions of Pa and power of 360W, then putting the medical substrate material into 5% acrylic acid solution for soaking for 2h, finally washing by using deionized water and drying in vacuum, and then uniformly fixing the dried and clean medical substrate material in a pipeline of a circulating flow device; the circulating flow device is formed by connecting a peristaltic pump and a circulating pipeline.
S2, preparing coating working solution, wherein the coating working solution comprises heparin sodium working solution with required concentration, albumin working solution and coupling agent working solution; the concentration of the prepared albumin working solution is 0.3g/L, and the pH value is adjusted to 4.5 by citric acid and sodium citrate; the concentration of the prepared heparin sodium working solution is 0.5g/L, and the pH value is adjusted to 2.5 by using citric acid and sodium hydroxide; the prepared coupling agent working solution is 1-ethyl-3- (3-dimethylaminopropyl) -carbodiimide solution (EDC) solution, the concentration is 0.4g/L, and the pH value is adjusted to 5.0 by using sodium dihydrogen phosphate and sodium hydroxide.
S3, generating a coating on the medical substrate material by a low-speed flow circulation method, which comprises the following steps:
a. washing the pipeline with deionized water with the pH value of 4.5, circulating with albumin working solution for 30min, washing with deionized water with the pH value of 4.5 for 2min, circulating with heparin sodium working solution for 15min, and washing with deionized water with the pH value of 4.5 for 2 min;
b. circulating with albumin working solution for 15min, washing with deionized water of pH4.5 for 2min, circulating with heparin sodium working solution for 15min, and washing with deionized water of pH4.5 for 2 min;
C. repeating the process of step b 5 times;
in the steps a-c, the flow rates of the three working liquids are controlled to be 1L/h-2L/h;
d. and circulating the coupling agent EDC solution prepared in the step S2 for 14h to generate the heparin-albumin composite coating on the medical substrate material.
Example 2
On the basis of the embodiment 1, the difference of the embodiment 1 is that the grafting agent adopts 5% dopamine; the concentration of the albumin working solution is 1.0g/L, the concentration of the heparin sodium working solution is 1.0g/L, and the pH value is 4.0; the coupling agent working solution is a saturated calcium chloride solution with the concentration of 1.0g/L and the pH value of 4.0.
Example 3
On the basis of the embodiment 1, the grafting agent is acrylamide with 5% concentration, which is different from the embodiment 1; the concentration of the albumin working solution is 0.1g/L, the concentration of the heparin sodium working solution is 0.1g/L, and the pH value is 2.0; the coupling agent working solution is 1-ethyl-3- (3-dimethylaminopropyl) -carbodiimide solution (EDC) with the concentration of 0.1g/L, and the pH value is 2.0.
The performance of the resulting heparin-albumin coating was tested by several test assays as follows:
Performing a water contact angle test on the heparin-albumin composite coating material generated on the medical substrate material:
heparin/albumin is a hydrophilic molecule that, when grafted, results in a change in the hydrophilicity of the nitinol surface. Dropping 20 uL of purified water on the surface of the sample, respectively shooting the contact section of the water and the surface of the sample at 0, 10, 20, 30, 40, 50 and 60s after dropping, obtaining contact angle data of different time points, and calculating the average contact angle by fitting. As can be seen from the attached figure 1, the contact angle of the medical substrate material before the heparin-albumin composite coating is generated is more than 80 degrees, the contact angle after the heparin-albumin composite coating is generated is 51 degrees, and the test shows that the hydrophilicity of the material after the heparin-albumin composite coating is generated on the medical substrate material is greatly improved.
The anticoagulant coating material is subjected to heparin content and durability tests:
1) preparing a standard heparin sodium solution;
2) preparing toluidine blue solution;
3) mixing and oscillating standard heparin solution with known content and freshly prepared toluidine blue solution according to a certain volume for 3 min;
4) adding n-hexane, shaking for 3min, taking out, measuring the absorbance at 623nm with a spectrophotometer, and drawing an absorbance-heparin standard curve;
5) immersing a sample to be detected in PBS, eluting and shaking 1, 2, 3, 4, 7, 10, 14, 17, 21, 25 and 30 days at 37 ℃, and taking out;
6) soaking the eluted sample in a freshly prepared toluidine blue solution, shaking for 4 hours at room temperature, and taking out the solution to measure the absorbance at the wavelength of 623 nm;
7) heparin durability was calculated according to a standard curve.
As can be seen from FIG. 2, the heparin-albumin composite coating produced on the medical substrate material of the present invention has a heparin content of 8mg/cm when just produced3After 30 days of detection, the heparin content is 7.2mg/cm3The heparin-albumin composite coating prepared by the preparation method has strong durability, and the heparin content can be maintained for a long time, so that the good anticoagulant activity can be maintained for a long time.
Through the tests 1 and 2, the heparin-albumin composite coating is generated on the medical substrate material by adopting the preparation method of the invention, the hydrophilicity and the durability are good, and the good anticoagulant activity can be kept for a long time. The preparation method of the invention has simple and convenient working procedures, short production period, high production efficiency and low production cost, and the prepared coating has good uniformity and high control accuracy of the thickness of the coating, and the performances of the coating in all aspects are far better than those of the prior similar products.
Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (10)
1. A preparation method of a composite coating for surface modification of medical materials is characterized by comprising the following steps:
s1, polishing the surface of the medical substrate material, sequentially putting the medical substrate material into acetone and absolute ethyl alcohol for ultrasonic cleaning, treating the polished and cleaned medical substrate material with plasma, taking out the medical substrate material, putting the medical substrate material into a grafting agent solution for soaking for 2-6 h, finally cleaning with deionized water and drying in vacuum to obtain the surface-modified medical substrate material;
s2, preparing coating working solution, wherein the coating working solution comprises heparin sodium working solution with required concentration, albumin working solution and coupling agent working solution;
s3, generating a coating on the medical substrate material by a low-speed flow circulation method, which comprises the steps of depositing heparin and albumin on the medical substrate material by the coating working solution configured in the step S2 in a low-speed flow circulation mode, carrying out chemical grafting by a coupling agent, and enabling the heparin-albumin composite coating to be stably combined with the medical substrate material to generate the coating, wherein in the coating preparation process, each parameter of the low-speed flow circulation, namely the circulation sequence, the circulation frequency, the flow speed or the circulation time of each working solution, is regulated and controlled, so that the thickness of the generated coating is controlled.
2. The method for preparing the composite coating for the surface modification of the medical material as claimed in claim 1, wherein the medical substrate material is one of stainless steel, titanium alloy, cobalt-based alloy and nickel titanium shape memory alloy.
3. The method for preparing the composite coating for surface modification of the medical material as claimed in claim 1, wherein the plasma treatment method for the medical substrate material in step S1 is as follows: vacuum at 3X 10 of background-2 ～5×10-2Using N under the conditions of Pa and power of 300-400W2Or Ar gas plasma is used for treating the surface of the medical substrate material for 8-20 min.
4. The method for preparing a composite coating for surface modification of medical materials according to claim 1, wherein the grafting agent in step S1 is selected from one or a mixture of several of dopamine, acrylic acid, acrylamide and polyethylene glycol.
5. The preparation method of the composite coating for the surface modification of the medical material according to claim 1, wherein the concentration of the heparin sodium working solution is 0.10-1.0 g/L, and the pH value is 2.0-5.0.
6. The method for preparing the composite coating for the surface modification of the medical material according to claim 1, wherein the concentration of the albumin working solution is 0.10 g/L to 1.0g/L, and the pH is 2.0 to 5.0.
7. The preparation method of the composite coating for the surface modification of the medical material, according to claim 1, wherein the working solution of the coupling agent is a 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide or saturated calcium chloride solution, the concentration is 0.10 g/L-1.0 g/L, and the pH is 2.0-5.0.
8. The method for preparing a composite coating for surface modification of medical materials according to claim 1, wherein the method for circulating each working fluid in the low-speed flow circulation method described in step S3 is: before the first circulation, the circulation pipeline is firstly washed by deionized water, then the albumin working solution is used for circulation in sequence, then the deionized water is used for washing, then the heparin sodium working solution is used for circulation, and then the deionized water is used for washing, when the second circulation is carried out, the albumin working solution is used for circulation, then the deionized water is used for washing, then the heparin sodium working solution is used for circulation, the repeated circulation is carried out for 3-5 times, and finally the coupling agent working solution is used for circulation, so that the heparin-albumin composite coating with the required thickness is generated.
9. The method for preparing the composite coating for the surface modification of the medical material according to claim 1, wherein in the step S3, the circulation time of the albumin working solution, the heparin sodium working solution and the cross-linking agent working solution is 5-60 min, and the flow rate of the three working solutions is 1L/h-2L/h.
10. The method for preparing the composite coating for surface modification of medical materials according to claim 1, wherein the thickness of the produced heparin-albumin composite coating is controlled to be 1-500 μm.
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| CN114634763A (en) * | 2022-03-21 | 2022-06-17 | 东莞市人民医院 | Cross-linked material with protein coating and preparation method thereof |
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