CN115109187A - Hydrophilic polymer for inhibiting generation of bacterial biofilm as well as preparation method and application thereof - Google Patents
Hydrophilic polymer for inhibiting generation of bacterial biofilm as well as preparation method and application thereof Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F226/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen
- C08F226/06—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen by a heterocyclic ring containing nitrogen
- C08F226/10—N-Vinyl-pyrrolidone
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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
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/08—Materials for coatings
- A61L29/085—Macromolecular materials
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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
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
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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
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
- A61L29/16—Biologically active materials, e.g. therapeutic substances
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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
- A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
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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
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
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Abstract
The invention belongs to the technical field of biomedical high molecular materials, relates to synthesis of a hydrophilic polymer, and particularly relates to a hydrophilic polymer for inhibiting generation of a bacterial biofilm, and a preparation method and application thereof. The hydrophilic polymer is prepared by quaternary polymerization of methacrylic acid sulfonic acid zwitterionic monomer, N-vinyl pyrrolidone, hydroxyethyl methacrylate and polymerizable polyethylene glycol monomethyl ether. The hydrophilic polymer is compounded with the blocked isocyanate to form a hydrophilic coating solution capable of inhibiting the generation of bacterial biofilms. The medical catheter with the hydrophilic lubricating surface and the characteristic of inhibiting the generation of bacterial biomembranes is obtained by coating the hydrophilic coating solution on the medical catheter by dip coating and thermal crosslinking technology. The hydrophilic polymer prepared by the invention has the characteristics of hydrophilicity and inhibition of generation of bacterial biofilms. The method for preparing the hydrophilic coating solution is simple, wide in applicable base material range, simple to operate, easy for industrial production and has potential application in the field of biomedical materials.
Description
Technical Field
The invention belongs to the technical field of biomedical high molecular materials, relates to synthesis of a hydrophilic polymer, and particularly relates to a hydrophilic polymer for inhibiting generation of a bacterial biofilm, and a preparation method and application thereof.
Background
With the interpenetration and development of modern life science, material science, medicine, engineering and other subjects, biomedical materials, an important subject which makes important contribution to human health and obtains important development, is more and more generally concerned by people, and becomes a hot spot for competitive research and development of countries in the world. The surface lubricity, inhibition of bacterial biofilm formation and biocompatibility of biomedical materials such as implanted medical devices are critical in clinical use. The biomedical material can rub with human tissues in the process of being inserted into a human body, so that the pain of a patient is increased; second, initial adhesion of bacteria to the surface of the biomedical material can result in the formation of a biofilm that protects the bacteria from the host immune system, thereby causing surgical site infection and posing a serious threat to the health of the patient.
In addition, surgical site infections are the most common surgical complications, accounting for approximately 40% of all healthcare-related infections and 5% of all surgical complications. Resulting in further surgical intervention, prolonged treatment time, and unexpectedly high medical costs. It is generally accepted that initial adhesion of bacteria to the surface of the biomaterial and biofilm formation caused by bacterial adhesion are the primary causes of surgical site infection. Once the biofilm forms, it protects the bacteria from the host immune system, making surgical site infection a problematic issue. Therefore, inhibiting initial bacterial adhesion and biofilm formation on the surface of biomedical materials is an effective strategy to reduce the incidence of surgical site infection.
However, the following problems are generally encountered in the research of the coating material for inhibiting the generation of the biofilm in the related art: one is the lack of consideration for the biocompatibility of zwitterionic type coating materials; secondly, the fixing and preparation method of the hydrophilic polymer coating is complicated and complicated, and the coating has the risk of falling off due to insufficient binding force between the coating and the base material. Thirdly, the related technology that the zwitterion is combined with the hydrophilic substance so as to endow the coating with lubricity and inhibit the generation of bacterial biofilm is less. Therefore, it is necessary to combine zwitterions and hydrophilic substances in a simple way to achieve the preparation of a lubricant coating that inhibits bacterial biofilm formation and is compatible with hydrophilicity.
Disclosure of Invention
Aiming at the problems, the invention provides a hydrophilic polymer for inhibiting the generation of bacterial biofilms, and a preparation method and application thereof. The method specifically comprises the following steps: the invention provides a hydrophilic polymer for inhibiting the generation of bacterial biofilms, which is characterized by having the following structural formula:
wherein: e. f, g and h are the number of repeating units of each monomer.
Further, the present invention provides a method for producing a hydrophilic polymer that inhibits the production of bacterial biofilm, comprising the steps of:
preparing polymerizable polyethylene glycol monomethyl ether in the step (1):
respectively adding a certain amount of polyethylene glycol monomethyl ether, acryloyl chloride and acetonitrile solution into a reaction vessel, heating to 80 ℃, adding a certain amount of triethylamine into the reaction vessel, and continuously heating for reaction for 5 hours at the temperature of 80 ℃. After the reaction was stopped, the reaction solution was slowly cooled to room temperature. Then, slowly dripping the reaction liquid into anhydrous ether while stirring to obtain a large amount of light yellow precipitate, filtering the precipitate, washing the precipitate with anhydrous methanol for multiple times, and drying the precipitate in a vacuum drying oven for 24 hours to obtain white solid powder-shaped polymerizable polyethylene glycol monomethyl ether. The average molecular weight of the polyethylene glycol monomethyl ether is 200-1000.
Step (2) preparation of hydrophilic polymer for inhibiting bacterial biofilm formation:
respectively adding a certain amount of zwitterionic monomer of methacrylic acid sulfobetaine, a hydrophilic monomer of N-vinylpyrrolidone, a crosslinking monomer of hydroxyethyl methacrylate, the polymerizable polyethylene glycol monomethyl ether monomer prepared in the step (1) and a certain amount of water-soluble initiator into an aqueous solution to form a mixed solution, and heating to 60 ℃ under the protection of nitrogen to react for 5 hours to obtain a transparent flowing liquid crude product. And (3) putting the crude product into a vacuum drying oven for drying for 24h, washing for multiple times by using absolute ethyl alcohol, removing unreacted monomers, then putting into the vacuum drying oven for continuously drying for 24h, and obtaining a white solid powder hydrophilic polymer capable of inhibiting the generation of bacterial biofilms.
Further, the preparation method of the hydrophilic polymer for inhibiting the generation of the bacterial biofilm is characterized in that the molar weight of the zwitterionic monomer of the sulfobetaine methacrylate, the hydrophilic monomer of the N-vinylpyrrolidone, the crosslinking monomer of the hydroxyethyl methacrylate and the polymerizable polyethylene glycol monomethyl ether monomer in the step (2) is 0.2-0.4mmol, 2-5mmol, 0.1-0.3mmol and 1-3mmol respectively. The water-soluble initiator is any one of a mixture of potassium persulfate and sodium bisulfite or a mixture of ammonium persulfate and sodium bisulfite, and the content of the initiator is 0.5 percent of the total mass of each monomer.
Further, the present invention provides a hydrophilic coating solution for inhibiting bacterial biofilm formation, which is prepared by using the hydrophilic polymer for inhibiting bacterial biofilm formation, characterized in that the hydrophilic coating solution is prepared by dissolving the hydrophilic polymer for inhibiting bacterial biofilm formation in a mixed solution of an organic solvent and water, and then adding blocked isocyanate to the solution.
Further, the hydrophilic coating solution is characterized in that the hydrophilic polymer for inhibiting the generation of the bacterial biofilm accounts for 2-5% of the total mass of the hydrophilic coating solution; the blocked isocyanate accounts for 0.2-0.5% of the total mass of the hydrophilic coating solution. The organic solvent is any one or more of ethanol, isopropanol, acetone and diacetone alcohol.
Further, the invention provides application of the hydrophilic coating solution, which is characterized in that the hydrophilic coating solution is coated on the surface of the medical catheter by a dip coating mode and is solidified for 1 hour at 100 ℃, so that a hydrophilic polymer for inhibiting the generation of the bacterial biofilm in the hydrophilic coating solution and closed isocyanate are subjected to a thermal crosslinking reaction, and the medical catheter with the functionalized medical coating for inhibiting the generation of the bacterial biofilm on the surface is obtained.
The beneficial effects of the invention are:
1. the hydrophilic polymer for inhibiting the generation of the bacterial biofilm has the characteristics of hydrophilicity and inhibition of the generation of the bacterial biofilm. The method specifically comprises the following steps:
(1) the polymer formed by zwitterions can adsorb water to form a hydration layer through electrostatic interaction in a physiological environment, so that the polymer has good antibacterial adhesion and biocompatibility;
(2) PEO in polymerizable polyethylene glycol monomethyl ether is a flexible chain that can combine with water molecules in water to form a hydrated polyoxyethylene chain. At a solid water interface, polyoxyethylene can diffuse to a water phase through strong interaction with water molecules to form a hydrated polyoxyethylene layer, so that bacteria are prevented from stagnating and adhering on the surface of the biomedical material, and the generation of a biological film on the surface of the material is inhibited;
(3) the introduction of N-vinylpyrrolidone and hydroxyethyl acrylate increases the hydrophilicity and functionalizability of the polymer.
2. The hydrophilic coating solution capable of inhibiting the generation of the bacterial biofilm provided by the invention has a simple preparation method. The hydrophilic polymer for inhibiting the generation of the bacterial biofilm in the hydrophilic coating solution and isocyanate are crosslinked to form a three-dimensional network structure, and the hydrophilic polymer is attached to the surface of the catheter by virtue of intermolecular force, so that the hydrophilic polymer is strong in adhesive force, is not easy to fall off, is easy for industrial production, and has potential application in the field of biomedical materials.
3. The surface of the medical catheter provided by the invention has the hydrophilic lubrication function and also has the characteristic of inhibiting the generation of bacterial biofilms.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the drawings without creative efforts.
FIG. 1 is a molecular structure diagram of a hydrophilic polymer for inhibiting bacterial biofilm formation according to the present invention.
FIG. 2 is a scheme showing the synthesis route of hydrophilic polymers for inhibiting bacterial biofilm formation according to the present invention.
FIG. 3 is an infrared spectrum of a hydrophilic polymer for inhibiting bacterial biofilm formation according to the present invention.
FIG. 4 is a graph of the friction coefficient test of the medical catheter made in accordance with the present invention.
FIG. 5 is a graph showing the results of a test for inhibiting the formation of bacterial biofilm in an optimized medical catheter made according to the present invention.
Detailed Description
The invention will be further elucidated with reference to specific embodiments. It is to be understood that this invention is not limited to the following examples, which are commercially available from the public unless otherwise specified.
Example 1
Step (1) preparation of polymerizable polyethylene glycol monomethyl ethers with different molecular weights: firstly, 1mmol of polyethylene glycol monomethyl ether with an average molecular weight of 200, 1.1mmol of acryloyl chloride and 10ml of acetonitrile solution are respectively added into a 50ml round bottom flask, then the flask is placed in an oil bath and heated to 80 ℃, and then 1.1mmol of triethylamine is added for reaction for 5 h. After the reaction was stopped, the reaction solution was slowly cooled to room temperature. Then, the reaction solution was slowly dropped into anhydrous ether while stirring to obtain a large amount of pale yellow precipitate, and then the precipitate was filtered out and washed with anhydrous methanol several times, and dried in a vacuum drying oven for 24 hours to obtain a white solid powder.
Step (2) preparation of hydrophilic polymer for inhibiting bacterial biofilm formation: preparing the polymer by adopting a solution free radical polymerization method; firstly, 0.2mmol of [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide zwitterionic monomer, 2mmol of N-vinyl pyrrolidone, 0.1mmol of hydroxyethyl methacrylate, 1mmol of polymerizable polyethylene glycol monomethyl ether in the step (1), 0.5% of ammonium persulfate and sodium bisulfite are weighed and added into 6ml of aqueous solution, and the aqueous solution is heated to 60 ℃ under the protection of nitrogen to react for 5 hours, so as to obtain a transparent flowing liquid crude product; and (3) drying the reacted crude product in a vacuum drying oven for 24h, washing the crude product for multiple times by using absolute ethyl alcohol to remove unreacted monomers, and then putting the crude product in the vacuum drying oven for continuous drying for 24h to obtain a white solid powder hydrophilic polymer capable of inhibiting the generation of bacterial biofilms.
And (3) preparing a hydrophilic coating solution capable of inhibiting the generation of bacterial biofilms: firstly, adding the synthesized hydrophilic polymer into a mixed solution of isopropanol and water, stirring for 30 minutes at room temperature, then adding the blocked isocyanate, and continuing stirring for 10 minutes to obtain a hydrophilic coating solution capable of inhibiting the generation of bacterial biofilms. Wherein the mass of the polymer is 3 percent of the total mass of the hydrophilic coating solution, the mass of the blocked isocyanate is 0.5 percent of the total mass of the hydrophilic coating solution, and the mass of the solvent is 96.5 percent of the total mass of the hydrophilic coating solution. And (3) coating the hydrophilic coating solution on the surface of the medical catheter, and curing for 1h at 100 ℃ to obtain the medical catheter with the surface provided with the functional medical coating for inhibiting the generation of the bacterial biofilm.
Example 2
Step (1) the same procedure as in step (1) in example 1 was used except that the average molecular weight of polyethylene glycol monomethyl ether was 350.
Step (2) the same procedure as in step (2) of example 1 was followed, except that the amount of the zwitterionic monomer of [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide was 0.4mmol, the amount of N-vinylpyrrolidone was 5mmol, the amount of hydroxyethyl methacrylate was 0.1mmol, and the amount of the polymerizable polyethylene glycol monomethyl ether in step (1) was 1.5 mmol.
Step (3) the same method as in step (3) in example 1 was used, except that the mass of the polymer was 3% of the total mass of the hydrophilic coating solution, the mass of the blocked isocyanate was 0.3% of the total mass of the hydrophilic coating solution, and the mass of the solvent was 96.7% of the total mass of the hydrophilic coating solution.
Example 3
Step (1) the same procedure as in step (1) in example 1 was used except that the average molecular weight of polyethylene glycol monomethyl ether was 500.
Step (2) the same procedure as in step (2) of example 1 was followed, except that the amount of the zwitterionic monomer of [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide was 0.32mmol, the amount of N-vinylpyrrolidone was 4mmol, the amount of hydroxyethyl methacrylate was 0.3mmol, and the amount of the polymerizable polyethylene glycol monomethyl ether in step (1) was 1.5 mmol.
Step (3) the same procedure as in step (3) in example 1 was used, except that the mass of the polymer was 2% of the total mass of the hydrophilic coating solution, the mass of the blocked isocyanate was 0.3% of the total mass of the hydrophilic coating solution, and the mass of the solvent was 97.7% of the total mass of the hydrophilic coating solution.
Example 4
Step (1) the same procedure as in step (1) in example 1 was used except that the polyethylene glycol monomethyl ether had an average molecular weight of 750.
Step (2) the same procedure as in step (2) of example 1 was followed, except that the amount of the zwitterionic monomer of [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide was 0.3mmol, the amount of N-vinylpyrrolidone was 3mmol, the amount of hydroxyethyl methacrylate was 0.3mmol, and the amount of the polymerizable polyethylene glycol monomethyl ether in step (1) was 2 mmol.
Step (3) the same method as in step (3) in example 1 was used, except that the mass of the polymer was 2% of the total mass of the hydrophilic coating solution, the mass of the blocked isocyanate was 0.2% of the total mass of the hydrophilic coating solution, and the mass of the solvent was 97.8% of the total mass of the hydrophilic coating solution.
Example 5
Step (1) the same procedure as in step (1) in example 1 was used except that the average molecular weight of polyethylene glycol monomethyl ether was 1000.
Step (2) the same procedure as in step (2) of example 1 was followed, except that the amount of the zwitterionic monomer of [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide was 0.2mmol, the amount of N-vinylpyrrolidone was 4mmol, the amount of hydroxyethyl methacrylate was 0.2mmol, and the amount of the polymerizable polyethylene glycol monomethyl ether in step (1) was 3 mmol.
Step (3) the same procedure as in step (3) in example 1 was used, except that the mass of the polymer was 3% of the total mass of the hydrophilic coating solution, the mass of the blocked isocyanate was 0.2% of the total mass of the hydrophilic coating solution, and the mass of the solvent was 96.8% of the total mass of the hydrophilic coating solution.
Examples of the effects of the invention
The structural characterization of the hydrophilic polymer for inhibiting the generation of the bacterial biofilm and the performance test of the prepared medical catheter with the functional medical coating for inhibiting the generation of the bacterial biofilm on the surface are as follows.
Testing one: and (3) testing the infrared performance of the hydrophilic polymer for inhibiting the generation of the bacterial biofilm.
(1) The testing steps are as follows: firstly, 2-4mg of hydrophilic polymer solid powder is put into an agate mortar, 200-400mg of dried KBr powder is added, the mixture is uniformly ground, about 200mg of the mixed powder is moved into a pastille forming container by a stainless steel key, and the pastille is obtained by pressurizing for 30 seconds under 25 MPa. The obtained tablets were then placed on filter paper and dried by irradiation with infrared lamps to prevent water absorption. And then placing the ingot sheet on a shelf of a solid sample, inserting the sample shelf into a sample window of an infrared spectrometer, and closing the sample room to measure the infrared absorption spectrum of the hydrophilic polymer sample.
(2) And (3) testing results: as shown in fig. 3. The results show that: at 3419cm -1 Is a stretching vibration characteristic peak of polymer-OH; 2950cm -1 、2890cm -1 Is a polymer CH 3 、CH 2 C-H stretching vibration characteristic peak of (1); 1667cm -1 Is the stretching vibration characteristic peak of carbonyl in the polymer; 1422cm -1 、1462cm -1 Is a C-H in-plane bending vibration characteristic peak of the polymer; 1288cm -1 Is the stretching vibration characteristic peak of-C-O-C-in the polymer; 1206cm -1 Is a C-N stretching vibration characteristic peak of tertiary amine in the polymer; 1148cm -1 Is a characteristic peak of a sulfonic acid group in the polymer; furthermore, as can be seen from FIG. 3, 3000-3100cm -1 Has no characteristic peak of stretching vibration of unsaturated double bond C-H, thereby indicating that the polymer synthesis is successful and no monomer remains.
And (2) testing: and testing the friction coefficient of the medical catheter with the functionalized medical coating for inhibiting the generation of the bacterial biofilm on the surface.
(1) The testing steps are as follows: and (3) placing the completely coated and cured medical catheter on a friction coefficient tester for testing, wherein the test cycle number is 30 times. The method comprises the following specific steps:
firstly, a sample to be measured penetrates through an upper clamping buckle and a lower clamp, and a clamping screw is rotated to clamp the sample to be measured. Then, test parameters are set, and the test is carried out for 30 times. Clicking a 'clamping' button of a program interface to enable two films of the clamp to be close to a sample to be tested, observing the value of the clamping force in the interface, clicking a 'start testing' button when the clamping force of the sample to be tested is 0.000, stopping testing after 30 times of testing, and deriving friction coefficient test data.
(2) And (3) testing results: as shown in fig. 4. The results show that: the medical catheter prepared by the scheme provided by the invention has good stability. In particular, the medical catheter prepared by the scheme provided by the embodiment 5 has optimal performance, and the surface of the medical catheter has good lubricity and stability, so that the medical catheter can meet the technical requirements of a catheter lubricating coating. It is worth noting that: the technology is not invariable and certain changes may be made with reference to the embodiments and still fall within the scope of the invention.
And (3) testing: testing of inhibition of bacterial biofilm formation by medical catheters having a functionalized medical coating on the surface thereof.
And testing the film forming amount of the bacterial biofilm by adopting a crystal violet staining method.
(1) And (3) testing: 3 medical catheters prepared in example 5 and 3 medical catheters without treatment (specification 16Fr, length 1.5 cm) were taken, sterilized by ethylene oxide, and placed in 3X 107cfu/ml E.coli bacterial suspension. Culturing at 37 deg.C for 48h, wherein 24h later, replacing fresh bacterial liquid. After 48h of culture, the tube was taken out, washed with 20mL of sterile water for 3 times, and stained with 1% crystal violet for 20 minutes. And (4) after dyeing is finished, soaking the tube body in sterile water to remove free dye which is not combined with the bacterial biofilm. And then, 95% ethanol is used for decoloring crystal violet combined with the bacterial biofilm on the surface of the tube, and the OD value is measured at 595nm to indicate the film forming amount of the bacterial biofilm.
(2) And (3) testing results: as shown in fig. 5. The results show that: compared with the untreated medical catheter, the medical catheter prepared by the scheme provided by the invention has the advantages that the generation amount of the bacterial biofilm on the surface of the medical catheter can be reduced by about 85%, and the medical catheter has excellent performance of inhibiting the generation of the bacterial biofilm.
It should be understood that the above detailed description of the present invention is only for illustrating the present invention and is not limited by the technical solutions described in the embodiments of the present invention, and those skilled in the art should understand that the present invention can be modified or substituted equally to achieve the same technical effects; as long as the use requirements are met, the method is within the protection scope of the invention.
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Claims (6)
2. A method for preparing the hydrophilic polymer for inhibiting bacterial biofilm formation of claim 1, comprising the steps of:
preparing polymerizable polyethylene glycol monomethyl ether in the step (1):
respectively adding a certain amount of polyethylene glycol monomethyl ether, acryloyl chloride and acetonitrile solution into a reaction vessel, heating to 80 ℃, adding a certain amount of triethylamine into the reaction vessel, and continuously heating and reacting for 5 hours at the temperature of 80 ℃;
after the reaction is stopped, slowly cooling the reaction solution to room temperature; then slowly dripping the reaction liquid into anhydrous ether while stirring to obtain a large amount of light yellow precipitate, filtering the precipitate, washing the precipitate with anhydrous methanol for multiple times, and drying the precipitate in a vacuum drying oven for 24 hours to obtain white solid powdery polymerizable polyethylene glycol monomethyl ether; the average molecular weight of the polyethylene glycol monomethyl ether is 200-1000;
step (2) preparation of hydrophilic polymer for inhibiting bacterial biofilm formation:
respectively adding a certain amount of zwitterionic monomer of methacrylic acid sulfobetaine, a hydrophilic monomer of N-vinylpyrrolidone, a crosslinking monomer of hydroxyethyl methacrylate, the polymerizable polyethylene glycol monomethyl ether monomer prepared in the step (1) and a certain amount of water-soluble initiator into an aqueous solution to form a mixed solution, and heating to 60 ℃ under the protection of nitrogen to react for 5 hours to obtain a transparent flowing liquid crude product; and (3) putting the crude product into a vacuum drying oven for drying for 24h, washing for multiple times by using absolute ethyl alcohol, removing unreacted monomers, then putting into the vacuum drying oven for continuously drying for 24h, and obtaining a white solid powder hydrophilic polymer capable of inhibiting the generation of bacterial biofilms.
3. The preparation method according to claim 2, characterized in that the molar amounts of the zwitterionic monomer of sulfobetaine methacrylate, the hydrophilic monomer of N-vinylpyrrolidone, the crosslinking monomer of hydroxyethyl methacrylate and the polymerizable polyethylene glycol monomethyl ether monomer in the step (2) are 0.2-0.4mmol, 2-5mmol, 0.1-0.3mmol and 1-3mmol, respectively; the water-soluble initiator is any one of a mixture of potassium persulfate and sodium bisulfite or a mixture of ammonium persulfate and sodium bisulfite, and the content of the initiator is 0.5 percent of the total mass of each monomer.
4. A hydrophilic coating solution for inhibiting the formation of a bacterial biofilm, which is prepared by using the hydrophilic polymer for inhibiting the formation of a bacterial biofilm according to claim 1, and is prepared by dissolving the hydrophilic polymer for inhibiting the formation of a bacterial biofilm in a mixed solution of an organic solvent and water, and then adding a blocked isocyanate to the solution.
5. The hydrophilic coating solution of claim 4, wherein the hydrophilic polymer for inhibiting bacterial biofilm formation comprises 2% to 5% of the total mass of the hydrophilic coating solution; the blocked isocyanate accounts for 0.2 to 0.5 percent of the total mass of the hydrophilic coating solution; the organic solvent is any one or more of ethanol, isopropanol, acetone and diacetone alcohol.
6. The use of the hydrophilic coating solution according to claim 5, wherein the hydrophilic coating solution is applied to the surface of the medical catheter by dip coating and cured at 100 ℃ for 1 hour to allow the hydrophilic polymer inhibiting the formation of the bacterial biofilm in the hydrophilic coating solution to thermally crosslink with the blocked isocyanate, thereby obtaining the medical catheter having the functionalized medical coating on the surface thereof inhibiting the formation of the bacterial biofilm.
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