Dextran backbone zwitterionic polyamino acid side chain brush polymers, preparation and use thereof

Abstract

The present application provides a kind of dextran main chain zwitterionic polyamino acid side chain brush polymer and its preparation and application, the dextran main chain zwitterionic polyamino acid side chain brush polymer provided by the present application can be used to prepare antibacterial coating, when the antibacterial coating is contacted with water molecule, the hydration of hydroxyl group of dextran and zwitterionic group of polyamino acid occurs simultaneously, at this time, the hydration layer is formed on the surface of coating to prevent the initial adhesion of bacteria and the non-specific adsorption of protein;When bacteria infect material surface, the cationic group of polyamino acid can destroy the structure of bacterial cell membrane, at this time, the coating shows bactericidal activity.The present application constructs the antibacterial coating based on brush polymer, non-leaching, anti-sticking and bactericidal dual-functional antibacterial coating on the surface of polymer medical device through crosslinking reaction, the preparation process is simple, the equipment demand is low, easy to operate, and the feasibility is high.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of antibacterial coating materials, and particularly relates to a brush-shaped polymer with a dextran main chain and zwitterionic polyamino acid side chains, and preparation and application thereof. BACKGROUND

[0002] Bacterial infection caused by pathogenic bacteria seriously threatens human health and life, and bacterial infection has become one of the main causes of human death. Hospitals are the main place where bacterial infection occurs and originates, and most of the hospital infections are caused by medical instrument-related infections. The adhesion, colonization and reproduction of bacteria on the surface of medical instruments, especially the surface of implantable / interventional medical instruments, easily lead to the formation of bacterial biofilm on the surface of the materials, which is the main cause of medical instrument-related infections. China is a populous country and the aging is serious, and the patients, mainly the elderly, often need to receive various diagnostic and treatment measures during hospitalization, such as tracheal intubation, urinary catheterization, central venous catheterization, bone implant materials, etc. The surfaces of these materials provide a platform for bacterial adhesion and biofilm formation. Once the biofilm is formed on the surface of the material, it is difficult to remove and treat, causing continuous and repeated infections in patients, which not only increases the morbidity and mortality of patients, but also causes huge economic losses to patients and society. Therefore, it is of great urgency to prevent and treat medical instrument-related infections.

[0003] In view of the problem of medical instrument-related infections, researchers have developed coating materials with antibacterial adhesion function (referred to as antibacterial adhesion coating) and coating materials with bactericidal function (referred to as bactericidal coating). The antibacterial adhesion coating in the prior art can only inhibit the initial adhesion of bacteria on the surface of the material, and bacteria can overcome the water on the surface of the coating to cause bacterial adhesion. Such coating does not have bactericidal function, and bacteria will continue to proliferate and eventually lead to the formation of biofilm. In addition, the bactericidal coating cannot remove the dead bacteria and their debris after killing the bacteria in contact with the surface. These substances cover the surface of the coating and shield the bactericidal function of the coating, so that the coating reduces or completely loses the bactericidal activity. New pathogenic bacteria are easily adhered and proliferated on the surface of these substances to form biofilm. The adhesion of dead bacteria and their debris on the surface of the bactericidal coating also easily causes immune inflammatory response of the human body. Moreover, the bactericidal coating also has problems such as high cytotoxicity and poor biocompatibility.

[0004] Therefore, how to design a coating material with antibacterial adhesion and bactericidal functions, and without toxicity and immune inflammatory response to human cells and tissues, so as to achieve the prevention and treatment of medical instrument-related infections, especially implantable / interventional medical instrument-related infections, has become one of the focuses of many forward-looking researchers in the field. SUMMARY

[0005] To solve the above technical problems, the present application aims to provide a dextran main chain zwitterionic polyamino acid side chain brush polymer and its preparation and application.

[0006] The dextran main chain zwitterionic polyamino acid side chain brush polymer provided by the present application can be used to prepare an antibacterial coating, which, when in contact with water molecules, simultaneously hydrates the hydroxyl groups of dextran and the zwitterionic groups of polyamino acid, at which time a hydration layer is formed on the surface of the coating to prevent the initial adhesion of bacteria and the non-specific adsorption of proteins; when bacteria infect the surface of the material, the cationic groups of polyamino acid can destroy the structure of the bacterial cell membrane, at which time the coating exhibits bactericidal activity.

[0007] The above object of the present application is achieved by the following technical solutions:

[0008] The present application provides a dextran main chain zwitterionic polyamino acid side chain brush polymer, and the structural formula of the dextran main chain zwitterionic polyamino acid side chain brush polymer is shown as formula (I):

[0009]

[0010] wherein x is an integer from 1 to 2000, y is an integer from 1 to 2000, and n is an integer from 1 to 1000.

[0011] x and y are the number of dextran units, and n is the degree of polymerization of polyamino acid, and the configuration of polyamino acid is L type, D type or D / L type.

[0012] The present application provides a preparation method of a dextran main chain zwitterionic polyamino acid side chain brush polymer, comprising the following steps:

[0013] (1) dissolving monomers and cystamine dihydrochloride in a first solvent to obtain a first polymer intermediate shown as formula (II) after ring-opening polymerization; the monomers are γ-(3-methylthiopropyl)-L-glutamate-N-carboxylic anhydride and / or γ-(3-methylthiopropyl)-D-glutamate-N-carboxylic anhydride;

[0014] (2) dissolving the first polymer intermediate obtained in step (1) and tris(2-carboxyethyl)phosphine in a first solvent to obtain a second polymer intermediate shown as formula (III) after reduction;

[0015] (3) dissolving dextran and maleic anhydride in a second solvent to obtain a third polymer intermediate shown as formula (IV) after esterification;

[0016] (4) dissolving the second polymer intermediate obtained in step (2) and the third polymer intermediate obtained in step (3) in a second solvent, and performing a Michael addition reaction to obtain a fourth polymer intermediate represented by formula (V);

[0017] (5) dissolving the fourth polymer intermediate obtained in step (4) and 2-bromoacetic acid in a third solvent, and performing an alkylation reaction to obtain the dextran backbone zwitterionic polyamino acid side chain brush-shaped polymer represented by formula (I);

[0018] The structural formulae of the above formula (I), formula (II), formula (III), formula (IV) and formula (V) are as follows:

[0019]

[0020]

[0021] wherein x is an integer of 1-2000, y is an integer of 1-2000, and n is an integer of 1-1000.

[0022] Further, in step (1), the molar ratio of the monomer to cystamine dihydrochloride is (1-1000):1, preferably (1-100):1.

[0023] Further, in step (1), the first solvent is selected from one or more of dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, tetrahydrofuran, dichloromethane, chloroform and water.

[0024] Further, in step (1), the temperature of the ring-opening polymerization reaction is 0-100°C.

[0025] Further, in step (1), the time of the ring-opening polymerization reaction is 0.1-100 h.

[0026] Further, in step (1), after the ring-opening polymerization reaction, a precipitation step is further included.

[0027] Further, in step (2), the molar ratio of the first polymer intermediate to tris(2-carboxyethyl)phosphine is 1:(1-100).

[0028] Further, in step (2), the ratio of the mass of the first polymer intermediate to the volume of the first solvent is (1-200) mg:1 mL.

[0029] Further, in step (2), the ratio of the mass of the tris(2-carboxyethyl)phosphine to the volume of the first solvent is (1-200) mg:1 mL.

[0030] Further, in step (2), the first solvent is selected from one or more of dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, tetrahydrofuran, dichloromethane, chloroform and water.

[0031] Further, in step (2), the temperature of the reduction reaction is 20-80°C.

[0032] Further, in step (2), the time of the reduction reaction is 12-72h.

[0033] Further, in step (3), the molar ratio of the dextran and maleic anhydride is 1:(1-50).

[0034] Further, in step (3), the ratio of the mass of the dextran to the volume of the second solvent is (1-200) mg: 1 mL.

[0035] Further, in step (3), the ratio of the mass of the maleic anhydride to the volume of the second solvent is (1-200) mg: 1 mL.

[0036] Further, in step (3), the second solvent is selected from one or more of dimethyl sulfoxide, triethylamine, N,N-dimethylformamide (DMF) and N,N-dimethylacetamide.

[0037] Further, in step (3), the temperature of the esterification reaction is 20-80°C.

[0038] Further, in step (3), the time of the esterification reaction is 12-72h.

[0039] Further, in step (4), the molar ratio of the second polymer intermediate and the third polymer intermediate is (1-100): 1.

[0040] Further, in step (4), the ratio of the mass of the second polymer intermediate to the volume of the second solvent is (1-200) mg: 1 mL.

[0041] Further, in step (4), the ratio of the mass of the third polymer intermediate to the volume of the second solvent is (1-200) mg: 1 mL.

[0042] Further, in step (4), the second solvent is selected from one or more of dimethyl sulfoxide, triethylamine, N,N-dimethylformamide and N,N-dimethylacetamide.

[0043] Further, in step (4), the temperature of the Michael addition reaction is 20-80°C.

[0044] Further, in step (4), the time of the Michael addition reaction is 12-72 h.

[0045] Further, in step (5), the molar ratio of the fourth polymer intermediate to 2-bromoacetic acid is 1:(1-100).

[0046] Further, in step (5), the mass of the fourth polymer intermediate to the volume of the third solvent is (1-1000) mg:1 mL.

[0047] Further, in step (5), the mass of the 2-bromoacetic acid to the volume of the third solvent is (1-1000) mg:1 mL.

[0048] Further, in step (5), the third solvent is selected from one or more of dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide and water.

[0049] Further, in step (5), the temperature of the alkylation reaction is 30-100℃.

[0050] Further, in step (5), the time of the alkylation reaction is 12-72 h.

[0051] The present application also protects the use of the dextran backbone zwitterionic polyamino acid side chain brush polymer of the first aspect in the preparation of an antibacterial coating, a medical device.

[0052] The third aspect of the present application provides an antibacterial coating comprising the dextran backbone zwitterionic polyamino acid side chain brush polymer of the first aspect.

[0053] The antibacterial coating provided by the present application has a three-dimensional network structure in which the dextran backbone zwitterionic polyamino acid side chain brush polymers within the molecule and / or between the molecules of the dextran backbone zwitterionic polyamino acid side chain brush polymers are crosslinked to each other.

[0054] Compared with the prior art, the antibacterial coating provided by the present application has antibacterial adhesion and sterilization functions. When the antibacterial coating contacts with water molecules, the hydroxyl groups of the dextran and the zwitterionic groups of the polyamino acid simultaneously hydrate, at which time a hydration layer is formed on the surface of the coating to prevent the initial adhesion of bacteria and the non-specific adsorption of proteins. When bacteria infect the surface of the material, the cationic groups of the polyamino acid can destroy the structure of the bacterial cell membrane, at which time the coating exhibits sterilization activity.

[0055] Further, the thickness of the antibacterial coating is 0.005-100 μm.

[0056] The fourth aspect of the present application provides a method for preparing the antibacterial coating of the third aspect, comprising the following steps:

[0057] S1. Dissolving the zwitterionic polyamino acid side chain brush polymer with dextran backbone of the first aspect of the present application and a cross-linking agent in a solvent to obtain an antibacterial coating solution after cross-linking reaction;

[0058] S2. Coating the antibacterial coating solution obtained in step S1 on a substrate to obtain the antibacterial coating on the substrate.

[0059] Further, in step S1, the concentration of the zwitterionic polyamino acid side chain brush polymer with dextran backbone in the antibacterial coating solution is 0.1-20 wt%, and the concentration of the cross-linking agent in the antibacterial coating solution is 0.1-20 wt%.

[0060] Further, in step S1, the cross-linking agent is selected from one or more of 2-(3,4-dihydroxyphenyl)ethylamine, D-3,4-dihydroxyphenylalanine, L-3,4-dihydroxyphenylalanine and L-3,4-dihydroxyphenylalanine hydrochloride.

[0061] Further, in step S1, the solvent is selected from one or more of water, Tris buffer, ethanol, propanol, butanol, isopropanol, toluene, phthalate, ethyl acetate, dimethyl sulfoxide, tetrahydrofuran, acetone, cyclohexanone, butanone, n-heptane, heptane, cyclohexane, dichloromethane and trichloromethane.

[0062] Further, in step S1, after dissolving the zwitterionic polyamino acid side chain brush polymer with dextran backbone of the first aspect of the present application and the cross-linking agent in the solvent, the step of mixing for 0.1-2 h is further included.

[0063] Further, in step S1, the cross-linking reaction includes free radical reaction, oxidation reaction and Michael addition reaction.

[0064] Further, in step S1, the temperature of the cross-linking reaction is 20-60℃.

[0065] Further, in step S1, the time of the cross-linking reaction is 12-72 h.

[0066] Further, in step S2, the coating method includes dipping, brushing and spraying.

[0067] Further, the material of the substrate in step S2 is selected from one or more of polyethylene, polyvinyl chloride, polypropylene, polybutylene, polyurethane, polyimide, natural rubber, silicone rubber, latex, thermoplastic elastomer, polytetrafluoroethylene, perfluoroethylene propylene copolymer, polystyrene, polycarbonate, polyether ether ketone and acrylonitrile-butadiene-styrene plastic.

[0068] The fifth aspect of the present application provides a medical device comprising the antibacterial coating of the third aspect.

[0069] Further, the medical device is mainly a polymer-based medical device, including a medical catheter.

[0070] The present application is based on the mechanism of initial bacterial adhesion and biofilm formation. Bacterial infection on the surface of a medical device often begins with the initial adhesion of bacteria, which then continuously breeds and eventually evolves into a bacterial biofilm infection. Therefore, the antibacterial coating material needs to have corresponding prevention and treatment functions corresponding to the bacterial infection process. In the initial bacterial adhesion stage, the antibacterial coating should have anti-adhesion function and also consider biocompatibility. Once bacterial adhesion and infection occur, the antibacterial coating should have the ability to relieve and treat bacterial infection. The brush-shaped polymer provided by the present application has a hydrophilic main chain with multiple hydroxyl groups and a hydrophilic side chain with zwitterionic groups. Compared with the antibacterial linear polymer coating, the dual hydration of the main chain and the side chain has higher antibacterial adhesion performance. Compared with the bactericidal linear polymer coating, the zwitterionic polymer side chains in the brush-shaped polymer can synergize to improve the bactericidal activity of the cationic groups in the polymer. At the same time, compared with the antibacterial medical device releasing bactericides, this antibacterial method of fixing the coating on the surface of the material to prevent and treat bacterial infection through contact sterilization can prevent the antibacterials from entering the human body blood, tissue fluid, etc., avoid cell damage, and has higher biological safety.

[0071] The beneficial effects of the present application are:

[0072] The brush-shaped polymer with a dextran main chain and a zwitterionic polyamino acid side chain provided by the present application can be used to prepare an antibacterial coating. When the antibacterial coating contacts with water molecules, the hydroxyl groups of dextran and the zwitterionic groups of polyamino acid simultaneously hydrate, at which time a hydration layer is formed on the surface of the coating to prevent the initial adhesion of bacteria and the non-specific adsorption of proteins. When bacteria infect the surface of the material, the cationic groups of polyamino acid can destroy the structure of bacterial cell membrane, at which time the coating shows bactericidal activity.

[0073] The application constructs a brush-shaped polymer-based, non-leaching, anti-sticking and sterilization dual-functional antibacterial coating on the surface of a high polymer medical device through a cross-linking reaction. The preparation process is simple, the equipment requirement is low, the operation is easy, and the feasibility is high. The experimental results show that the surface treated by the coating provided by the application has better hydrophilicity, and the water contact angle is significantly reduced, which is due to the fact that the hydrophilic groups in the main chain and the side chain of the brush-shaped polymer can all be combined with water, that is, double water combination. The antibacterial experimental results show that the brush-shaped polymer coating surface can effectively prevent initial bacterial adhesion and efficiently kill bacteria contacting the coating surface. The cytotoxicity experimental results show that the brush-shaped polymer coating does not produce toxicity to mammalian cells. BRIEF DESCRIPTION OF DRAWINGS

[0074] Figure 1 Synthesis route diagram of the brush-shaped polymer with a zwitterionic polyamino acid side chain and a dextran main chain.

[0075] Figure 2 GPC diagram of the first polymer intermediate 1 H NMR diagram.

[0076] Figure 3 H NMR diagram of the second polymer intermediate 1

[0077] Figure 4 GPC diagram of the first polymer intermediate and the second polymer intermediate

[0078] Figure 5 H NMR diagram of the fourth polymer intermediate 1

[0079] Figure 6 H NMR diagram of the brush-shaped polymer with a zwitterionic polyamino acid side chain and a dextran main chain 1

[0080] Figure 7 SEM diagram of the surface of the urinary catheter with the antibacterial coating prepared in Example 1 after bacterial adhesion test.

[0081] Figure 8 SEM diagram of the surface of the urinary catheter without modification of the antibacterial coating after bacterial adhesion test.

[0082] Figure 9 Data diagram of the number of colonies on the culture dish after sterilization performance test of the surface of the urinary catheter with the antibacterial coating prepared in Example 1 and the surface of the urinary catheter without modification of the antibacterial coating.

[0083] Figure 10 ​​​This is a statistical graph showing the percentage of cell viability of mouse embryonic fibroblasts after covering the surface of the urinary catheter with the antibacterial coating prepared in Example 1 and the surface of the urinary catheter without the antibacterial coating.

[0084] Figure 11 This is a statistical graph showing the percentage of cell viability after covering human embryonic kidney cells on the surface of the urinary catheter with the antibacterial coating prepared in Example 1 and the surface of the urinary catheter without the antibacterial coating.

[0085] Figure 12 This is a graph showing the biofilm growth rate data of the catheter with an antibacterial coating prepared in Example 1, the catheter with a mixed cross-linked coating prepared in Comparative Example 1, the catheter with a polydopamine coating prepared in Comparative Example 2, and the catheter without antibacterial coating modification after being cultured in Staphylococcus aureus culture medium.

[0086] Figure 13 This is a graph showing the biofilm growth rate data of the catheter with an antibacterial coating prepared in Example 1, the catheter with a mixed cross-linked coating prepared in Comparative Example 1, the catheter with a polydopamine coating prepared in Comparative Example 2, and the catheter without antibacterial coating modification after being cultured in Escherichia coli culture medium.

[0087] Figure 14 This is a graph showing the protein adsorption rate data of the urinary catheter with an antibacterial coating prepared in Example 1, the urinary catheter with a polydopamine coating prepared in Comparative Example 2, the urinary catheter with an antibacterial coating prepared in Comparative Example 3, and the urinary catheter without antibacterial coating modification after incubation in a fibrinogen solution.

[0088] Figure 15 CLSM images of the urinary catheter with antibacterial coating prepared in Example 1, the urinary catheter with antibacterial coating prepared in Comparative Example 3, and the urinary catheter without antibacterial coating modification after culture in mouse mononuclear macrophage leukemia cells.

[0089] Figure 16 This is a data graph showing the cell coverage of the catheter with antibacterial coating prepared in Example 1, the catheter with antibacterial coating prepared in Comparative Example 3, and the catheter without antibacterial coating modification after culture in mouse mononuclear macrophage leukemia cells. DETAILED DESCRIPTION

[0090] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this invention pertains. The terms used in this specification of the present invention are for the purpose of describing specific embodiments only and are not intended to limit the present invention. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0091] The present application provides a preparation method of a dextran main chain zwitterionic polyamino acid side chain brush polymer, a synthetic route of which is shown in Figure 1 The preparation method comprises the following steps:

[0092] (1) dissolving monomers and cystamine dihydrochloride in a first solvent, and performing ring-opening polymerization to obtain a first polymer intermediate (polyamino acid connected by a disulfide bond), a hydrogen spectrum (H NMR) diagram of which is shown in 1 Figure 2

[0093] (2) dissolving the polyamino acid connected by a disulfide bond and tris(2-carboxyethyl)phosphine in the first solvent, and performing reduction to obtain a second polymer intermediate (polyamino acid with a thiol end group), a hydrogen spectrum (H NMR) diagram of which is shown in 1 Figure 3 A gel permeation chromatography (GPC) diagram of the first polymer intermediate and the second polymer intermediate is shown in Figure 4

[0094] (3) dissolving dextran and maleic anhydride in a second solvent, and performing esterification to obtain a third polymer intermediate (maleic acid modified dextran);

[0095] (4) dissolving the polyamino acid with a thiol end group and the maleic acid modified dextran in the second solvent, and performing Michael addition to obtain a fourth polymer intermediate (polyamino acid modified dextran), a hydrogen spectrum (H NMR) diagram of which is shown in 1 Figure 5

[0096] (5) dissolving the polyamino acid modified dextran and 2-bromoacetic acid in a third solvent, and performing alkylation to obtain the dextran main chain zwitterionic polyamino acid side chain brush polymer, a hydrogen spectrum (H NMR) diagram of which is shown in 1 Figure 6

[0097] The present application provides a preparation method of an antibacterial coating, comprising the following steps:

[0098] S1. dissolving the dextran main chain zwitterionic polyamino acid side chain brush polymer provided by the present application and a crosslinking agent in a solvent, and performing crosslinking to obtain an antibacterial coating liquid;

[0099] S2. coating the antibacterial coating liquid obtained in step S1 on a substrate to obtain the antibacterial coating on the substrate.

[0100] The present application will be further described in conjunction with the drawings and specific examples, so that those skilled in the art can better understand the present application and implement it, but the examples are not limiting to the present application.​​​​​​​​

[0101] The experimental methods used in the following examples are conventional methods, and the materials, reagents, etc. used are commercially available unless otherwise specified.

[0102] Example 1

[0103] A method for preparing a urinary catheter with an antibacterial coating, comprising the following steps:

[0104] S1. Dissolve 120 mg of zwitterionic polyamino acid side chain brush polymer of dextran backbone and 8 mg of 2-(3,4-dihydroxyphenyl)ethylamine in 60 mL of Tris buffer, stir at room temperature for 10 min, and obtain an antibacterial coating solution after crosslinking reaction;

[0105] S2. Soak the silica gel material urinary catheter in the antibacterial coating solution obtained in step S1 for 24 h, then take it out, repeatedly rinse the surface of the material with deionized water, and dry at room temperature to obtain a urinary catheter with an antibacterial coating.

[0106] In step S1, the zwitterionic polyamino acid side chain brush polymer of dextran backbone is prepared by the following method:

[0107] (1) Dissolve 3.1 g of γ-(3-methylthiopropyl)-L-glutamate-N-carboxyanhydride and 140 mg of cystamine dihydrochloride in 20 mL of N,N-dimethylformamide, and perform ring-opening polymerization reaction at room temperature for 24 h, then precipitate with diethyl ether, and vacuum dry to obtain a disulfide-linked polyamino acid;

[0108] (2) Dissolve 0.27 g of the disulfide-linked polyamino acid and 30 mg of tris(2-carboxyethyl)phosphine in 10 mL of N,N-dimethylformamide, and perform reduction reaction at room temperature for 24 h, then precipitate with water, and vacuum dry to obtain a polyamino acid with a thiol end group;

[0109] (3) Dissolve 0.5 g of dextran and 9 g of maleic anhydride in 50 mL of DMF solvent, add 36 μL of triethylamine, and perform esterification reaction at 60°C for 24 h, then precipitate with isopropyl alcohol, dialyze in a 3500 Da dialysis bag for 72 h, and freeze-dry to obtain maleic acid-modified dextran;

[0110] (4) Dissolve 0.21 g of the polyamino acid with a thiol end group and 14 mg of the maleic acid-modified dextran in 3 mL of dimethyl sulfoxide, and perform Michael addition reaction at room temperature for 24 h, then precipitate with water, and vacuum dry to obtain polyamino acid-modified dextran;

[0111] (5) 0.2 g of the polyamino acid-modified dextran and 5 g of 2-bromoacetic acid were dissolved in N,N-dimethylformamide, and an alkylation reaction was performed at room temperature. After 48 h, dialysis was performed in a 50000 Da dialysis bag for 72 h, and the dextran main chain zwitterionic polyamino acid side chain brush-shaped polymer was obtained by lyophilization.

[0112] Example 2

[0113] A method for preparing a urinary catheter with an antibacterial coating, comprising the following steps:

[0114] S1. 120 mg of the dextran main chain zwitterionic polyamino acid side chain brush-shaped polymer and 8 mg of 2-(3,4-dihydroxyphenyl)ethylamine were dissolved in 60 mL of Tris buffer, stirred at room temperature for 10 min, and a crosslinking reaction was performed to obtain an antibacterial coating solution;

[0115] S2. The silica gel material urinary catheter was immersed in the antibacterial coating solution obtained in step S1 for 24 h, then taken out and repeatedly washed with deionized water, and dried at room temperature to obtain a urinary catheter with an antibacterial coating.

[0116] In step S1, the dextran main chain zwitterionic polyamino acid side chain brush-shaped polymer was prepared by the following method:

[0117] (1) 3.1 g of γ-(3-methylthiopropyl)-L-glutamate-N-carboxyanhydride and 70 mg of cystamine dihydrochloride were dissolved in 20 mL of N,N-dimethylformamide, and a ring-opening polymerization reaction was performed at room temperature for 24 h. After precipitation with diethyl ether, vacuum drying was performed to obtain a disulfide bond connected polyamino acid;

[0118] (2) 0.27 g of the disulfide bond connected polyamino acid and 30 mg of tris(2-carboxyethyl)phosphine were dissolved in 10 mL of N,N-dimethylformamide, and a reduction reaction was performed at room temperature. After 24 h, precipitation was performed with water, and vacuum drying was performed to obtain a thiol-terminated polyamino acid;

[0119] (3) 0.5 g of dextran and 9 g of maleic anhydride were dissolved in 50 mL of DMF solvent, 36 μL of triethylamine was added, and an esterification reaction was performed at 60°C for 24 h. After precipitation with isopropyl alcohol, dialysis was performed in a 3500 Da dialysis bag for 72 h, and lyophilization was performed to obtain a maleic acid-modified dextran;

[0120] (4) 0.21 g of the thiol-terminated polyamino acid and 14 mg of the maleic acid-modified dextran were dissolved in 3 mL of dimethyl sulfoxide, and a Michael addition reaction was performed at room temperature. After 24 h, precipitation was performed with water, and vacuum drying was performed to obtain a polyamino acid-modified dextran;

[0121] (5) 0.2 g of the polyamino acid-modified dextran and 5 g of 2-bromoacetic acid were dissolved in N,N-dimethylformamide, and an alkylation reaction was performed at room temperature. After 48 h, dialysis was performed in a 50000 Da dialysis bag for 72 h, and the dextran main chain zwitterionic polyamino acid side chain brush-shaped polymer was obtained by lyophilization.

[0122] Example 3

[0123] A method for preparing a urinary catheter with an antibacterial coating, comprising the following steps:

[0124] S1. 120 mg of the dextran main chain zwitterionic polyamino acid side chain brush-shaped polymer and 8 mg of 2-(3,4-dihydroxyphenyl)ethylamine were dissolved in 60 mL of Tris buffer, stirred at room temperature for 10 min, and a crosslinking reaction was performed to obtain an antibacterial coating solution;

[0125] S2. The silica gel material urinary catheter was immersed in the antibacterial coating solution obtained in step S1 for 24 h, then taken out and repeatedly washed with deionized water, and dried at room temperature to obtain a urinary catheter with an antibacterial coating.

[0126] In step S1, the dextran main chain zwitterionic polyamino acid side chain brush-shaped polymer was prepared by the following method:

[0127] (1) 3.1 g of γ-(3-methylthiopropyl)-L-glutamate-N-carboxyanhydride and 140 mg of cystamine dihydrochloride were dissolved in 20 mL of N,N-dimethylformamide, and a ring-opening polymerization reaction was performed at room temperature for 24 h. After precipitation with diethyl ether, vacuum drying was performed to obtain a disulfide bond connected polyamino acid;

[0128] (2) 0.27 g of the disulfide bond connected polyamino acid and 30 mg of tris(2-carboxyethyl)phosphine were dissolved in 10 mL of N,N-dimethylformamide, and a reduction reaction was performed at room temperature. After 24 h, precipitation was performed with water, and vacuum drying was performed to obtain a thiol-terminated polyamino acid;

[0129] (3) 0.5 g of dextran and 5 g of maleic anhydride were dissolved in 50 mL of DMF solvent, 36 μL of triethylamine was added, and an esterification reaction was performed at 60°C for 24 h. After precipitation with isopropyl alcohol, dialysis was performed in a 3500 Da dialysis bag for 72 h, and lyophilization was performed to obtain a maleic acid-modified dextran;

[0130] (4) 0.21 g of the thiol-terminated polyamino acid and 14 mg of the maleic acid-modified dextran were dissolved in 3 mL of dimethyl sulfoxide, and a Michael addition reaction was performed at room temperature. After 24 h, precipitation was performed with water, and vacuum drying was performed to obtain a polyamino acid-modified dextran;

[0131] (5) 0.2 g of the polyamino acid-modified dextran and 5 g of 2-bromoacetic acid were dissolved in N,N-dimethylformamide, and an alkylation reaction was performed at room temperature. After 48 h, dialysis was performed in a 50000 Da dialysis bag for 72 h, and the dextran main chain zwitterionic polyamino acid side chain brush-shaped polymer was obtained by lyophilization.

[0132] Example 4

[0133] A method for preparing a urinary catheter with an antibacterial coating, comprising the following steps:

[0134] S1. 120 mg of the dextran main chain zwitterionic polyamino acid side chain brush-shaped polymer and 8 mg of 2-(3,4-dihydroxyphenyl)ethylamine were dissolved in 60 mL of Tris buffer, stirred at room temperature for 10 min, and a crosslinking reaction was performed to obtain an antibacterial coating solution;

[0135] S2. The silica gel material urinary catheter was immersed in the antibacterial coating solution obtained in step S1 for 24 h, then taken out and repeatedly washed with deionized water, and dried at room temperature to obtain a urinary catheter with an antibacterial coating.

[0136] In step S1, the dextran main chain zwitterionic polyamino acid side chain brush-shaped polymer was prepared by the following method:

[0137] (1) 3.1 g of γ-(3-methylthiopropyl)-D-glutamate-N-carboxyanhydride and 140 mg of cystamine dihydrochloride were dissolved in 20 mL of N,N-dimethylformamide, and a ring-opening polymerization reaction was performed at room temperature for 24 h. After precipitation with diethyl ether, vacuum drying was performed to obtain a disulfide bond connected polyamino acid;

[0138] (2) 0.27 g of the disulfide bond connected polyamino acid and 30 mg of tris(2-carboxyethyl)phosphine were dissolved in 10 mL of N,N-dimethylformamide, and a reduction reaction was performed at room temperature. After 24 h, precipitation was performed with water, and vacuum drying was performed to obtain a thiol-terminated polyamino acid;

[0139] (3) 0.5 g of dextran and 9 g of maleic anhydride were dissolved in 50 mL of DMF solvent, 36 μL of triethylamine was added, and an esterification reaction was performed at 60°C for 24 h. After precipitation with isopropyl alcohol, dialysis was performed in a 3500 Da dialysis bag for 72 h, and lyophilization was performed to obtain a maleic acid-modified dextran;

[0140] (4) 0.21 g of the thiol-terminated polyamino acid and 14 mg of the maleic acid-modified dextran were dissolved in 3 mL of dimethyl sulfoxide, and a Michael addition reaction was performed at room temperature. After 24 h, precipitation was performed with water, and vacuum drying was performed to obtain a polyamino acid-modified dextran;

[0141] (5) 0.2 g of the polyamino acid-modified dextran and 5 g of 2-bromoacetic acid were dissolved in N,N-dimethylformamide, and an alkylation reaction was performed at room temperature. After 48 h, dialysis was performed in a 50000 Da dialysis bag for 72 h, and the dextran main chain zwitterionic polyamino acid side chain brush-shaped polymer was obtained by lyophilization.

[0142] Example 5

[0143] A method for preparing a urinary catheter with an antibacterial coating, comprising the following steps:

[0144] S1. 120 mg of the dextran main chain zwitterionic polyamino acid side chain brush-shaped polymer and 8 mg of 2-(3,4-dihydroxyphenyl)ethylamine were dissolved in 60 mL of Tris buffer, stirred at room temperature for 10 min, and a crosslinking reaction was performed to obtain an antibacterial coating solution;

[0145] S2. The silica gel material urinary catheter was immersed in the antibacterial coating solution obtained in step S1 for 24 h, then taken out and repeatedly washed with deionized water, and dried at room temperature to obtain a urinary catheter with an antibacterial coating.

[0146] In step S1, the dextran main chain zwitterionic polyamino acid side chain brush-shaped polymer was prepared by the following method:

[0147] (1) 3.1 g of γ-(3-methylthiopropyl)-L-glutamate-N-carboxyanhydride and 140 mg of cystamine dihydrochloride were dissolved in 20 mL of N,N-dimethylformamide, and a ring-opening polymerization reaction was performed at room temperature for 24 h. After precipitation with diethyl ether, vacuum drying was performed to obtain a disulfide bond connected polyamino acid;

[0148] (2) 0.27 g of the disulfide bond connected polyamino acid and 30 mg of tris(2-carboxyethyl)phosphine were dissolved in 10 mL of N,N-dimethylformamide, and a reduction reaction was performed at room temperature. After 24 h, precipitation was performed with water, and vacuum drying was performed to obtain a thiol-terminated polyamino acid;

[0149] (3) 0.5 g of dextran and 9 g of maleic anhydride were dissolved in 50 mL of DMF solvent, 36 μL of triethylamine was added, and an esterification reaction was performed at 60°C for 24 h. After precipitation with isopropyl alcohol, dialysis was performed in a 3500 Da dialysis bag for 72 h, and lyophilization was performed to obtain a maleic acid-modified dextran;

[0150] (4) 0.21 g of the thiol-terminated polyamino acid and 14 mg of the maleic acid-modified dextran were dissolved in 3 mL of dimethyl sulfoxide, and a Michael addition reaction was performed at room temperature. After 24 h, precipitation was performed with water, and vacuum drying was performed to obtain a polyamino acid-modified dextran;

[0151] (5) 0.2 g polyamino acid modified dextran and 5 g 2-bromoacetic acid were dissolved in N, N-dimethylformamide, and after the alkylation reaction at room temperature, the solution was dialyzed in a 50000 Da dialysis bag for 72 h, and after lyophilization, the brush-shaped polymer of the dextran main chain and zwitterionic polyamino acid side chains was obtained.

[0152] Comparative Example 1

[0153] A method for preparing a urinary catheter with a mixed cross-linked coating, comprising the following steps:

[0154] S1. 60 mg of maleic acid modified dextran, 60 mg of linear zwitterionic polyamino acid and 8 mg of 2-(3,4-dihydroxyphenyl)ethylamine were dissolved in 60 mL of Tris buffer, stirred at room temperature for 10 min, and after the cross-linking reaction, an antibacterial coating solution was obtained; the structure of the linear zwitterionic polyamino acid is as follows:

[0155]

[0156] S2. The silica gel material urinary catheter was immersed in the antibacterial coating solution obtained in step S1 for 24 h, then taken out, and the surface of the material was repeatedly washed with deionized water, and then dried at room temperature to obtain a urinary catheter with an antibacterial coating.

[0157] Comparative Example 2

[0158] A method for preparing a urinary catheter with a polydopamine coating, comprising the following steps:

[0159] S1. 60 mg of 2-(3,4-dihydroxyphenyl)ethylamine was dissolved in 30 mL of Tris buffer, stirred at room temperature for 10 min, and after the cross-linking reaction, an antibacterial coating solution was obtained;

[0160] S2. The silica gel material urinary catheter was immersed in the antibacterial coating solution obtained in step S1 for 24 h, then taken out, and the surface of the material was repeatedly washed with deionized water, and then dried at room temperature to obtain a urinary catheter with an antibacterial coating.

[0161] Comparative Example 3

[0162] A method for preparing a urinary catheter with an antibacterial coating (brush-shaped polymer coating based on mixed charge polyamino acid), comprising the following steps:

[0163] S1. 60 mg of dextran main chain poly(lysine-random-glutamic acid) side chain brush-shaped polymer and 4 mg of 2-(3,4-dihydroxyphenyl)ethylamine were dissolved in 30 mL of Tris buffer, stirred at room temperature for 10 min, and after the cross-linking reaction, an antibacterial coating solution was obtained; the structure of the dextran main chain poly(lysine-random-glutamic acid) side chain brush-shaped polymer is as follows:

[0164]

[0165] S2. The silicone catheter was immersed in the antibacterial coating solution obtained in step S1 for 24 h, then removed and rinsed with deionized water. The material was dried at room temperature to obtain a catheter with an antibacterial coating.

[0166] Test Example 1

[0167] The change in the water contact angle of the catheter surface before and after modification of the antibacterial coating was tested by the following method:

[0168] The water contact angle of the catheter surface of the catheter with the antibacterial coating prepared in Example 1-5 and the catheter without modification of the antibacterial coating was tested by using a water contact angle measuring instrument. Three points with a distance of 5 mm were tested for each sample, and a total of 6 readings were taken, and the arithmetic mean value was taken.

[0169] The test results are shown in Table 1:

[0170] Table 1

[0171] Contact angle before modification of antibacterial coating (°) Contact angle after modification of antibacterial coating (°) Example 1 101.2 21.5 Example 2 100.1 22.3 Example 3 103.2 26.3 Example 4 101.1 27.8 Example 5 101.2 23.2

[0172] As can be seen from Table 1, the water contact angle of the catheter surface after modification of the antibacterial coating is significantly smaller than that of the unmodified catheter surface, indicating that the antibacterial coating significantly enhances the hydrophilicity of the surface of the device.

[0173] Test Example 2

[0174] The bacterial adhesion test was performed on the surface of the catheter with the antibacterial coating prepared in Example 1 and the surface of the catheter without modification of the antibacterial coating.

[0175] The test method was as follows: the catheter with the antibacterial coating prepared in Example 1 and the catheter without modification of the antibacterial coating were immersed in a bacterial culture solution with a concentration of 1 x 10 8 After 48 h, they were taken out, immersed in a 2.5% glutaraldehyde aqueous solution at 4°C overnight, dehydrated with gradient ethanol, and finally observed for bacterial adhesion on the surface of the device by using a scanning electron microscope (SEM).

[0176] The test results are shown in Figure 7 and Figure 8 , the SEM image of the surface of the catheter with the antibacterial coating prepared in Example 1 after the bacterial adhesion test is shown in Figure 7 , and the SEM image of the surface of the catheter without modification of the antibacterial coating after the bacterial adhesion test is shown in Figure 8 As can be seen from the SEM images, the surface of the catheter with the antibacterial coating has almost no bacterial adhesion, while the surface of the catheter without modification of the antibacterial coating has a large amount of bacterial adhesion.

[0177] Test Example 3

[0178] The bactericidal performance test was conducted on the surface of the urinary catheter with the antibacterial coating prepared in Example 1 and the surface of the urinary catheter without the antibacterial coating.

[0179] The test method is as follows: the urinary catheter with antibacterial coating prepared in Example 1 and the urinary catheter without antibacterial coating are immersed in a solution with a concentration of 1×10 6 After 24 hours, the cells were taken out and the bacteria adhering to the surface were washed with sterile buffer solution and shaken for 0.5 hours. The bacterial suspension was diluted and plated on LB solid culture plates and cultured for 24 hours. The number of colonies on the culture plate was counted using a colony counter.

[0180] The test results are as follows Figure 9 As shown, Figure 9 The data graph of the number of colonies on the culture dish after the sterilization performance test of the catheter surface with antibacterial coating and the catheter surface without antibacterial coating prepared in Example 1 is shown. Figure 9 It can be seen that the surface of the catheter with antibacterial coating can effectively kill bacteria, while the surface of the catheter without antibacterial coating modification has no bactericidal performance.

[0181] Test Example 4

[0182] Cytotoxicity experiments were conducted on the surface of the urinary catheter with the antibacterial coating prepared in Example 1 and the surface of the urinary catheter without the antibacterial coating to verify the effect of the antibacterial coating modified device surface on the viability of mammalian cells.

[0183] The test method is as follows: the surface of the catheter with antibacterial coating prepared in Example 1 and the surface of the catheter without antibacterial coating are lightly covered with mouse embryonic fibroblasts (NIH 3T3) and human embryonic kidney cells (HEK293T), respectively, with a cell concentration of 1×10 6 After 24 hours, the catheter was removed and the cell viability was analyzed and calculated using the MTT assay.

[0184] The test results are as follows Figure 10 and Figure 11 As shown, Figure 10 This is a statistical chart of the percentage of cell viability of mouse embryonic fibroblasts after covering the surface of the catheter with antibacterial coating prepared in Example 1 and the surface of the catheter without antibacterial coating, Figure 11 The figure shows the percentage of cell viability of human embryonic kidney cells after covering the surface of the catheter with an antibacterial coating prepared in Example 1 and the surface of the catheter without antibacterial coating. It can be seen from the figure that the surface of the catheter with an antibacterial coating prepared in Example 1 and the surface of the catheter without antibacterial coating did not produce obvious toxicity to mammalian cells.

[0185] Test Example 5

[0186] The surfaces of the urinary catheter having the antibacterial coating prepared in Example 1, the urinary catheter having the mixed cross-linked coating prepared in Comparative Example 1, the urinary catheter having the polydopamine coating prepared in Comparative Example 2, and the urinary catheter not modified with the antibacterial coating were subjected to a performance test for biofilm formation.

[0187] The test method was as follows: Staphylococcus aureus and Escherichia coli were cultured overnight in LB broth at 37°C. Then, the Staphylococcus aureus suspension was diluted to 1 x 10 8 CFU·mL -1 The Escherichia coli suspension was diluted to the same concentration with M9 minimal medium.

[0188] The urinary catheter having the antibacterial coating prepared in Example 1, the urinary catheter having the mixed cross-linked coating prepared in Comparative Example 1, the urinary catheter having the polydopamine coating prepared in Comparative Example 2, and the urinary catheter not modified with the antibacterial coating were respectively immersed in a bacterial culture solution having a concentration of 1 x 10 8 Each group of the urinary catheters was set in triplicate, and incubated at 37°C for 48 hours. During the incubation, the fresh culture medium was replaced every 24 hours. After 48 hours, the culture medium was carefully aspirated, the urinary catheters were taken out, and gently washed with PBS buffer to remove the loose bacteria that had not formed biofilm. The urinary catheters were subjected to ultrasonic treatment for 5 minutes to disperse the living bacteria into the PBS buffer. Subsequently, the bacterial suspension was serially diluted to an appropriate concentration, and plated on agar plates. After 24 hours, colony counting was performed. The urinary catheter not modified with the antibacterial coating was used as a control group, and the biofilm growth rate of the control group was 100% to calculate the biofilm growth rate on the surface of the urinary catheter.

[0189] The test results are shown in Table 1, Figure 12 and Figure 13 Table 1 Figure 12 Figure 1 is a graph showing the biofilm growth rate data of the urinary catheter having the antibacterial coating prepared in Example 1, the urinary catheter having the mixed cross-linked coating prepared in Comparative Example 1, the urinary catheter having the polydopamine coating prepared in Comparative Example 2, and the urinary catheter not modified with the antibacterial coating after being cultured in the Staphylococcus aureus culture solution, Figure 13The biofilm growth rate data chart of the urinary catheter with antibacterial coating prepared in Example 1, the urinary catheter with mixed cross-linked coating prepared in Comparative Example 1, the urinary catheter with polydopamine coating prepared in Comparative Example 2 and the urinary catheter without antibacterial coating modification after being cultured in the E. coli culture solution can be seen from the chart, and it can be seen that the surface of the urinary catheter with antibacterial coating provided by the application can effectively inhibit the growth of different bacterial biofilms, and has significantly improved antibacterial biofilm formation performance compared with the surface of the mixed cross-linked coating.

[0190] Test Example 6

[0191] The adsorption rate of protein on the surface of the urinary catheter with antibacterial coating prepared in Example 1, the surface of the urinary catheter with polydopamine coating prepared in Comparative Example 2, the surface of the urinary catheter with antibacterial coating prepared in Comparative Example 3 and the surface of the urinary catheter without antibacterial coating modification was determined by BCA method.

[0192] The test method is as follows: the urinary catheter with antibacterial coating prepared in Example 1, the urinary catheter with polydopamine coating prepared in Comparative Example 2, the urinary catheter with antibacterial coating prepared in Comparative Example 3 and the urinary catheter without antibacterial coating modification are soaked in a fibrinogen (Fg) solution with a concentration of 2.5 mg·mL -1 at 37°C for 24 hours. Then, the surface of the instrument is gently cleaned with deionized water. Next, the instrument is soaked in a 2 wt.% SDS solution. Shake on a shaker for 2 hours, then ultrasonic treatment in an ice water bath for 1 hour to ensure that the protein adsorbed on the surface of the instrument is completely detached. Then, 100 μL of the protein solution is taken into a 96-well plate, and 100 μL of BCA reagent is added to each well. After the plate is incubated at 60°C for 1 hour, the absorbance value is read at a wavelength of 560 nm using an enzyme-linked immunosorbent assay instrument to determine the adsorption amount of the protein on the surface of the instrument. The urinary catheter without antibacterial coating modification is used as a control group, and the protein adsorption rate of the control group is 100%, so as to calculate the protein adsorption rate of the coating surface.

[0193] The test results are shown in Table 1, Figure 14 Figure 14 The protein adsorption rate data chart of the urinary catheter with antibacterial coating prepared in Example 1, the urinary catheter with polydopamine coating prepared in Comparative Example 2, the urinary catheter with antibacterial coating prepared in Comparative Example 3 and the urinary catheter without antibacterial coating modification after being incubated in the fibrinogen solution can be seen from the chart, Figure 14 ​It can be seen that the catheter surface prepared in Example 1 having an antibacterial coating (zwitterionic polyamino acid side chain brush polymer coating based on a dextran backbone) can effectively inhibit protein adsorption, and the catheter surface prepared in Comparative Example 3 having an antibacterial coating (brush polymer coating based on a mixed charge polyamino acid) has significantly improved anti-protein adsorption performance.

[0194] Test Example 7

[0195] The catheter surface prepared in Example 1 having an antibacterial coating, the catheter surface prepared in Comparative Example 3 having an antibacterial coating, and the catheter surface without modification of an antibacterial coating were tested for anti-mammalian cell adhesion performance by laser scanning confocal microscopy (CLSM).

[0196] The test method was as follows: the catheter prepared in Example 1 having an antibacterial coating, the catheter prepared in Comparative Example 3 having an antibacterial coating, and the catheter without modification of an antibacterial coating were immersed in a suspension of newly cultured mouse monocyte macrophage leukemia cells (RAW264.7) (5 x 10 4 The cells were incubated in a cell incubator at 37°C for 24 hours to promote cell adhesion and growth. Then, the fresh culture medium was replaced to ensure normal growth of the cells, and the incubation was continued in a cell incubator at 37°C for 24 hours. Then, the culture medium was aspirated, the device was removed, and the device surface was gently washed with PBS buffer to remove loosely adhered cells. Subsequently, the cells adhering to the catheter surface were stained with Hoechest 33258 reagent under light shielding conditions for 20 minutes. After that, the device surface was gently washed, and the cells adhering to the catheter surface were fixed with a PBS solution containing 4 wt.% paraformaldehyde. After 10 minutes, the device was gently washed with PBS buffer. The cells adhering to the catheter surface were observed by CLSM, and the cell coverage was calculated by Image J software.

[0197] The test results are shown in Figure 15 and Figure 16 Figure 15 CLSM images of the catheter prepared in Example 1 having an antibacterial coating, the catheter prepared in Comparative Example 3 having an antibacterial coating, and the catheter without modification of an antibacterial coating after culture in mouse monocyte macrophage leukemia cells, Figure 16 ​The cell coverage data chart of the urinary catheter with antibacterial coating prepared in Example 1, the urinary catheter with antibacterial coating prepared in Comparative Example 3 and the urinary catheter without modification of antibacterial coating after being cultured in mouse mononuclear macrophage leukemia cells, from which it can be seen that the surface of the urinary catheter with antibacterial coating (brush-shaped polymer coating based on zwitterionic polyamino acid side chain of dextran main chain) prepared in Example 1 can effectively inhibit the adhesion of mammalian cells on the surface of the instrument, and has significantly improved anti-cell adhesion performance compared with the surface of the urinary catheter with antibacterial coating (brush-shaped polymer coating based on mixed charge polyamino acid) prepared in Comparative Example 3.

[0198] Obviously, the above embodiments of the present application are only examples for clearly illustrating the present application, and are not intended to limit the embodiments of the present application. It should be understood by those skilled in the art that other different forms of changes or variations can be made on the basis of the above description. Here, it is not necessary and also impossible to exhaust all the embodiments. Any modification, equivalent replacement and improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the claims of the present application.

Claims

1. A dextran backbone zwitterionic polyamino acid side chain brush polymer characterized in that, The structure of the dextran main chain zwitterionic polyamino acid side chain brush polymer is shown as formula (I): Wherein, x is an integer of 1-2000, y is an integer of 1-2000, and n is an integer of 1-1000.

2. A method of preparing a dextran backbone zwitterionic polyamino acid side chain brush polymer, characterized in that, Comprising the following steps: (1) dissolving monomers and cystamine dihydrochloride in a first solvent, and performing ring-opening polymerization to obtain a first polymer intermediate shown as formula (II); the monomers are γ-(3-methylthiopropyl)-L-glutamate-N-carboxylic anhydride and / or γ-(3-methylthiopropyl)-D-glutamate-N-carboxylic anhydride; (2) dissolving the first polymer intermediate obtained in step (1) and tris(2-carboxyethyl)phosphine in a first solvent, and performing reduction to obtain a second polymer intermediate shown as formula (III); (3) dissolving dextran and maleic anhydride in a second solvent, and performing esterification to obtain a third polymer intermediate shown as formula (IV); (4) dissolving the second polymer intermediate obtained in step (2) and the third polymer intermediate obtained in step (3) in a second solvent, and performing Michael addition to obtain a fourth polymer intermediate shown as formula (V); (5) dissolving the fourth polymer intermediate obtained in step (4) and 2-bromoacetic acid in a third solvent, and performing alkylation to obtain the dextran main chain zwitterionic polyamino acid side chain brush polymer shown as formula (I); The structural formulas of the above formula (I), formula (II), formula (III), formula (IV) and formula (V) are as follows: Wherein, x is an integer of 1-2000, y is an integer of 1-2000, and n is an integer of 1-1000.

3. The preparation method according to claim 2, characterized in that In step (1), the molar ratio of the monomers to cystamine dihydrochloride is (1-1000):

1.

4. The production method according to claim 2, characterized by, In step (3), the molar ratio of the dextran to maleic anhydride is 1:(1-100).

5. The preparation method according to claim 2, characterized in that In step (4), the molar ratio of the second polymer intermediate to the third polymer intermediate is (1-100):

1.

6. An antimicrobial coating, characterized in that, The dextran main chain zwitterionic polyamino acid side chain brush polymer of claim 1.

7. A method of producing the antibacterial coating according to claim 6, characterized in that, Comprising the following steps: S1. dissolving the dextran main chain zwitterionic polyamino acid side chain brush polymer of claim 1 and a crosslinking agent in a solvent, and performing crosslinking to obtain an antibacterial coating liquid; S2. coating the antibacterial coating liquid obtained in step S1 on a substrate to obtain the antibacterial coating on the substrate.

8. The production method according to claim 7, characterized by, In step S1, the concentration of the dextran main chain zwitterionic polyamino acid side chain brush polymer in the antibacterial coating liquid is 0.1-20 wt%, and the concentration of the crosslinking agent in the antibacterial coating liquid is 0.1-20 wt%.

9. The preparation method according to claim 7, characterized in that In step S1, the crosslinking agent is selected from one or more of 2-(3,4-dihydroxyphenyl)ethylamine, D-3,4-dihydroxyphenylalanine, L-3,4-dihydroxyphenylalanine and L-3,4-dihydroxyphenylalanine hydrochloride.

10. A medical device, comprising: The antibacterial coating of claim 6.

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