Preparation method and application of gamma-polyglutamic acid-quaternary ammonium salt-mussel protein coating

Abstract

The application discloses a preparation method and application of a gamma-polyglutamic acid-quaternary ammonium salt-mussel protein coating, which is a polyamino acid complex formed through electrostatic self-assembly interaction of a negative-charged gamma-polyglutamic acid, a positive-charged cationic quaternary ammonium salt and a mussel protein; the gamma-polyglutamic acid is directly separated and purified through a microbial fermentation method; and the cationic quaternary ammonium salt is any one of benzalkonium chloride, dodecyltrimethylammonium bromide, dodecyltrimethylammonium chloride, hexadecyltrimethylammonium bromide. The coating can be used as an antibacterial coating on the surface of a medical instrument, and can effectively reduce the risk of acquired infection caused by various medical instruments; and the modification method is suitable for preventing bacterial infection caused by various medical instruments.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of biomedical materials, and particularly relates to a preparation method and application of a gamma-polyglutamic acid-quaternary ammonium salt-mussel protein coating. BACKGROUND

[0002] Bacterial reproduction on the surface of medical devices can cause certain biological pollution. In the field of biomedicine, immune rejection caused by bacterial pollution and poor biocompatibility not only affects the service life of medical devices, but also brings huge economic burden and medical safety problems. In recent years, scholars from various countries have summarized that when two ions with opposite charges reach charge balance, they can solve the problem of bacterial colonization to the greatest extent by using the principle of electrostatic self-assembly. Therefore, preventing biological pollution has very important research significance and application value.

[0003] In the field of biomedical applications, antibacterial coatings will directly contact body fluids or tissues in a physiological environment, so antibacterial coatings are required to have good biocompatibility. Polyethylene glycol is an amphoteric ion antibacterial material, but its shortcomings such as easy oxidation and metabolic toxicity have puzzled many researchers, thus limiting its application in biomedicine. In some current research reports, amphoteric ion graft modification mostly involves some complicated chemical reactions, which to some extent increases the uncontrollability of biomaterials in terms of safety.

[0004] CN111704856A discloses a gamma-polyglutamic acid-poly cation complex and a preparation method and application thereof. The gamma-polyglutamic acid-poly cation complex is formed by the interaction between a small molecular weight gamma-polyglutamic acid with negative charge and a poly cation compound with positive charge. The gamma-polyglutamic acid is obtained by microbial fermentation, and has a molecular weight in the range of 5000-10000 Dalton, preferably 5000 Dalton. The poly cation compound is any one of polylysine, carboxymethyl chitosan, chitosan quaternary ammonium salt, and polylysine hydrochloride. The complex can be used as an anti-pollution coating on the surface of medical devices, can stably adhere to the surface of medical devices, has a long action time, and can effectively isolate the growth of microorganisms on the surface of the device and inhibit the adhesion of microorganisms on the surface. The gamma-polyglutamic acid used in the complex is a pure product purified after microbial fermentation, and is expensive.

[0005] CN114452447A discloses a mussel protein-polyamino acid coating, including a mussel protein layer in contact with the surface of the device to be coated and a polyamino acid layer crosslinked with the mussel protein layer, and its preparation method includes providing a substrate to be coated, pretreating the surface thereof, then soaking the substrate at room temperature in a mussel protein solution, then taking it out and uniformly blowing dry under a nitrogen blower to obtain a mussel protein modified substrate; the obtained mussel protein modified substrate is immersed in a polyglutamic acid solution for self-assembly reaction, then taken out and uniformly blown dry under a nitrogen blower to obtain a mussel protein-polyamino acid coating on the surface of the substrate to be coated. The application enriches the method of polyelectrolyte self-assembly, expands the application of biological macromolecules on medical materials, and provides an integrated solution for the antibacterial and lubricating needs of medical catheters in practice.

[0006] Therefore, it is extremely important to develop a method for surface modification coating with low cost, universality, high biocompatibility and low toxic side effects. SUMMARY

[0007] The technical problem to be solved by the present application is to provide a preparation method and application of a gamma-polyglutamic acid-quaternary ammonium salt-mussel protein coating to solve the problems of how to stably combine, continuously antibacterial and reduce the cost of antibacterial coating on the surface of medical devices.

[0008] To solve the above technical problems, the gamma-polyglutamic acid-quaternary ammonium salt-mussel protein coating is prepared by the following method:

[0009] (1) Dissolve the positively charged quaternary ammonium salt compound in water, fully dissolve, then add gamma-polyglutamic acid supernatant under stirring conditions, and obtain gamma-polyglutamic acid-quaternary ammonium salt complex precipitate after the reaction is complete;

[0010] (2) The complex precipitate obtained in step (1) is subjected to solid-liquid separation, and the obtained solid part is washed with water and dried; preferably, plate and frame pressure filtration is used for solid-liquid separation;

[0011] (3) The obtained product after drying in step (2) is dissolved in an organic solvent with mussel protein to obtain a gamma-polyglutamic acid-quaternary ammonium salt-mussel protein coating,

[0012] The gamma-polyglutamic acid supernatant is prepared by the following method:

[0013] 1) Dilute the gamma-polyglutamic acid fermentation broth with deionized water, preferably dilute with equal amount of deionized water, mix diatomite and pearl powder, then perform solid-liquid separation to remove bacteria, and preferably remove bacteria by plate and frame pressure filtration to recover the liquid part;

[0014] 2) adding activated carbon to the liquid part obtained in step 1), stirring to decolorize, such as mechanical stirring for 0.5-1 h, and then performing solid-liquid separation to recover the liquid part, thereby obtaining the γ-polyglutamic acid clear solution, preferably, the filtrate obtained after decolorization by plate and frame pressure filtration is the γ-polyglutamic acid clear solution.

[0015] In step (1), the quaternary ammonium salt compound is any one of benzalkonium chloride, dodecyltrimethylammonium bromide, dodecyltrimethylammonium chloride, and cetyltrimethylammonium bromide; and the mussel protein is MFP-5 type mussel protein. To further save costs, the mussel protein is obtained by introducing the MFP-5 gene of Mytilus galloprovincialis into the genome of Escherichia coli for expression. Preferably, the quaternary ammonium salt compound is cetyltrimethylammonium bromide (CTAB).

[0016] Preferably, the quaternary ammonium salt compound (such as CTAB) is first dissolved by ultrasonic before forming the complex. The treatment step is as follows: dissolve CTAB with a mass fraction of 0.5%-3% in deionized water, and then perform ultrasonic dissolution for 30 min. Preferably, the mass fraction of CTAB is 1%.

[0017] Specifically, the yield of the γ-polyglutamic acid fermentation broth is 20-40 g / L, and the molecular weight of the γ-polyglutamic acid is 500-2000 kDa; the yield of the γ-polyglutamic acid fermentation broth is 20-40 g / L, and the molecular weight of the γ-polyglutamic acid is 500-2000 kDa; the amount of diatomite is 1-5 wt%, the amount of pearl powder is 1-5 wt%, and the amount of activated carbon is 0.5-3 wt%. Preferably, the yield of the γ-polyglutamic acid fermentation broth is 40 g / L, the mass fraction of diatomite is 2%, the mass fraction of pearl powder is 2%, and the mass fraction of activated carbon is 1%, and the optimal mechanical stirring time is 0.5 h.

[0018] In step (1), the γ-polyglutamic acid-quaternary ammonium salt complex is formed by first mechanically stirring the quaternary ammonium salt solution (such as CTAB solution) and then slowly adding the γ-polyglutamic acid. If the order is reversed, the complex may be "clumped". The stirring rate of the mechanical stirring is controlled at 200-300 rpm, and the time is 5-10 min. Preferably, the stirring rate is 250 rpm, and the time is 8 min.

[0019] The mass ratio of the γ-polyglutamic acid to the quaternary ammonium salt compound is 1:1-1:3, and the concentration of the mussel protein in the final system is 250-1000 μg / mL. Preferably, the concentration of the mussel protein is 500 μg / mL.

[0020] In step (3), the organic solvent is any one of ethanol, acetone, dichloromethane, dimethyl sulfoxide, dimethylformamide, tetrahydrofuran, and the mass fraction of the obtained product in the organic solvent after drying is 1-10%. Preferably, the organic solvent is ethanol. The mass fraction of the complex in the organic solvent is 1-10%. Preferably, the mass fraction of the complex is 5%.

[0021] The application further provides application of the above-mentioned gamma-polyglutamic acid-quaternary ammonium salt-mussel protein coating in preparation of an antibacterial coating.

[0022] The application also provides a preparation method of an antibacterial coating on the surface of a medical device. Specifically, the above-mentioned gamma-polyglutamic acid-quaternary ammonium salt-mussel protein coating is uniformly coated on the surface of the medical device, and then dried in an oven, so as to form the gamma-polyglutamic acid-quaternary ammonium salt-mussel protein antibacterial coating on the surface of the medical device.

[0023] Preferably, the temperature of the oven is 35-40℃, and the drying time is 30-60 min; preferably, the temperature of the oven is 40℃, and the drying time is 30 min.

[0024] The surface material of the medical device is polyurethane, polyvinyl chloride, silicone rubber, iron or titanium alloy, or magnesium alloy. Preferably, the polyurethane base material is used for medical catheters, and the titanium alloy base material is used for medical equipment.

[0025] The antibacterial coating of the application can be applied to the surface of a medical device.

[0026] Advantages: Compared with the prior art, the application has the following advantages:

[0027] (1) The application establishes an antibacterial coating which is simple to operate, has strong universality and firm stability. Traditional antibacterial coatings have some resistant or tolerant bacteria with the increase of the use cycle, thereby slowing down the antibacterial effect of the coating. The coating forms a killing protection mechanism on the surface after electrostatic self-assembly, thereby achieving the antibacterial purpose.

[0028] (2) The protein coating prepared by the application has high and sustained antibacterial performance and good stability. Moreover, the preparation method has mild conditions, simple operation, repeatability, and wide application prospect.

[0029] (3) The application overcomes the defect that the traditional process must use cosmetic-grade gamma-polyglutamic acid as the coating. In addition, the price of the quaternary ammonium salt cationic surfactant is low, thereby saving the production cost. BRIEF DESCRIPTION OF DRAWINGS

[0030] The above and / or other aspects of the application will become more apparent by describing in detail the preferred embodiments thereof with reference to the attached drawings.

[0031] Figure 1 SEM (scanning electron microscope) microstructure of the complex coating prepared for Examples 1-4;

[0032] Figure 2 ATR-FTIR (infrared spectroscopy) analysis of the complex coating prepared for Examples 1-4;

[0033] Figure 3 Evaluation results of cell compatibility of the complex coating prepared for Examples 1-4; DETAILED DESCRIPTION

[0034] The present application will be described in detail below through specific examples. The following examples are used to further illustrate the present application, but should not be construed as limiting the present application. If not specifically indicated, the technical means used in the examples are conventional means well known to those skilled in the art.

[0035] In the following examples, the mussel protein (MFP-5) can be prepared according to the genetic engineering bacteria construction method disclosed in CN116042502A.

[0036] The γ-polyglutamic acid fermentation broth used in the following examples is prepared by the method disclosed in CN111876364A to obtain a γ-polyglutamic acid fermentation broth with a yield of 30 g / L and an average molecular weight of 500 KDa.

[0037] Example 1

[0038] (1) 100 mL of γ-polyglutamic acid fermentation broth (polyglutamic acid molecular weight 500 KDa) with a yield of 30 g / L was diluted with 100 mL of deionized water, then 2% diatomite and 2% pearl powder were added and mixed thoroughly, and then sterilized by plate and frame pressure filtration, and the filtrate was recovered;

[0039] (2) The filtrate obtained in step (1) was added with 1 wt% activated carbon, and then mechanically stirred (200 rpm) for 0.5 h, and then decolorized by plate and frame pressure filtration, and the filtrate was recovered, which was the γ-polyglutamic acid clear liquid;

[0040] (3) 1% CTAB was dissolved in water, and then ultrasonically dissolved for 30 min, and then transferred into a mechanical stirrer, and then γ-polyglutamic acid clear liquid was slowly added while stirring at 200 rpm, and the mass ratio of γ-polyglutamic acid to quaternary ammonium salt compound was 1:1, and then γ-polyglutamic acid-CTAB complex precipitate was obtained after the reaction was completed;

[0041] (4) The complex precipitate obtained in step (3) was subjected to plate and frame pressure filtration, and then washed with water, and then dried at 40°C;

[0042] (5) The complex treated in step (4) is dissolved in 95% ethanol to prepare a γ-polyglutamic acid-CTAB solution with a mass fraction of 5%, and is mixed with mussel protein (MFP-5) to make the final concentration of the mussel protein in the system 500 μg / mL, to obtain an antibacterial coating, which is then uniformly coated on the surface of a polyurethane medical catheter and a titanium alloy substrate, and then dried in a 40°C oven for 30 min, so that a γ-polyglutamic acid-CTAB-mussel protein antibacterial coating (denoted as γ-PGA-CTAB-MFP) is formed on the surface of the polyurethane catheter and the titanium alloy substrate.

[0043] Example 2

[0044] (1) 100 mL of γ-polyglutamic acid fermentation liquor with a yield of 30 g / L is diluted with 100 mL of deionized water, and then mixed with 2% diatomite and 2% pearl powder by mass fraction, and then subjected to plate and frame pressure filtration to remove bacteria, and the filtrate is recovered;

[0045] (2) The filtrate obtained in step (1) is added with 1% activated carbon, and subjected to mechanical stirring for 0.5 h, and then subjected to plate and frame pressure filtration to remove color, and the γ-polyglutamic acid clear liquid is recovered.

[0046] (3) Benzalkonium chloride (BAC) is dissolved in water, and then ultrasonically dissolved for 30 min, and then transferred to mechanical stirring, and γ-polyglutamic acid clear liquid is slowly added while stirring, and then the γ-polyglutamic acid-BAC complex precipitate is obtained after the reaction is completed.

[0047] (4) The complex precipitate obtained in step (1) is subjected to plate and frame pressure filtration, and then washed with water and dried at 40°C, to obtain the product.

[0048] (5) The complex treated in step (4) is dissolved in 95% ethanol to prepare a γ-polyglutamic acid-BAC solution with a mass fraction of 5%. In addition, mussel protein (MFP-5) is mixed to make the final concentration of the mussel protein in the system 500 μg / mL, which is uniformly coated on the surface of a polyurethane medical catheter and a titanium alloy substrate, and then dried in a 40°C oven for 30 min, so that a γ-polyglutamic acid-BAC-mussel protein antibacterial coating (denoted as γ-PGA-BAC-MFP) is formed on the surface of the polyurethane catheter and the titanium alloy substrate.

[0049] Example 3

[0050] (1) 100 mL of γ-polyglutamic acid fermentation liquor with a yield of 30 g / L is diluted with 100 mL of deionized water, and then mixed with 2% diatomite and 2% pearl powder by mass fraction, and then subjected to plate and frame pressure filtration to remove bacteria, and the filtrate is recovered;

[0051] (2) The filtrate obtained in step (1) is added to 1% activated carbon and stirred mechanically for 0.5 h, and then subjected to plate and frame filter decolorization to recover the γ-polyglutamic acid clear solution.

[0052] (3) The dodecyltrimethylammonium bromide (DTAB) is dissolved in water, and after being fully dissolved by ultrasonic for 30 min, it is moved into mechanical stirring, and the γ-polyglutamic acid clear solution is slowly added while stirring, and after the reaction is completed, the γ-polyglutamic acid-DTAB complex precipitate is obtained.

[0053] (4) The complex precipitate obtained in step (1) is subjected to plate and frame filter pressing, and after being washed with water, it is dried at 40°C to obtain;

[0054] (5) The complex after step (4) treatment is dissolved in 95% ethanol to prepare a γ-polyglutamic acid-DTAB solution with a mass fraction of 5%. In addition, the mussel protein (MFP-5) is blended to make the final concentration of the mussel protein in the system be 500 μg / mL, which is uniformly coated on the surface of the polyurethane medical catheter and titanium alloy substrate, and then dried in a 40°C oven for 30 min, and the γ-polyglutamic acid-DTAB-mussel protein antibacterial coating (recorded as: γ-PGA-DTAB-MFP) is formed on the surface of the polyurethane medical catheter and titanium alloy substrate.

[0055] Example 4

[0056] (1) 100 mL of γ-polyglutamic acid fermentation liquid with a yield of 30 g / L is diluted with 100 mL of deionized water, and then mixed with 2% diatomite and 2% pearl powder to remove bacteria by plate and frame filter pressing, and the filtrate is recovered;

[0057] (2) The filtrate obtained in step (1) is added to 1% activated carbon and stirred mechanically for 0.5 h, and then subjected to plate and frame filter decolorization to recover the γ-polyglutamic acid clear solution.

[0058] (3) The dodecyltrimethylammonium bromide (DTAB) is dissolved in water, and after being fully dissolved by ultrasonic for 30 min, it is moved into mechanical stirring, and the γ-polyglutamic acid clear solution is slowly added while stirring, and after the reaction is completed, the γ-polyglutamic acid-DTAB complex precipitate is obtained.

[0059] (4) The complex precipitate obtained in step (1) is subjected to plate and frame filter pressing, and after being washed with water, it is dried at 40°C to obtain;

[0060] (5) The complex treated in step (4) was dissolved in 95% ethanol to prepare a γ-polyglutamic acid-DTAC solution with a mass fraction of 5%. In addition, the mussel protein (MFP-5) was blended to make the final concentration of the mussel protein in the system 500 μg / mL, and then uniformly coated on the surface of the polyurethane medical catheter and titanium alloy substrate. After drying in a 40°C oven for 30 min, the γ-polyglutamic acid-DTAC-mussel protein antibacterial coating (denoted as γ-PGA-DTAC-MFP) was formed on the surface of the polyurethane medical catheter and titanium alloy substrate.

[0061] Example 5

[0062] The complex coating prepared in the above Examples 1-4 was respectively subjected to scanning electron microscopy (SEM) analysis according to the following experimental process. Before checking the morphology under a high-resolution field emission scanning electron microscope (JEOL SEM-7100-EDX), the sample to be tested was prepared on the sample stage after gold spraying, and the coating morphology was observed under an acceleration voltage of 1 kV. The topographic image was obtained under a scale of 2 μm. The following Figure 1 is the topography after measurement. As can be seen from the figure, the coating is stably combined with the substrate and uniformly distributed.

[0063] Example 6

[0064] The complex coating prepared in the above Examples 1-4 was respectively subjected to infrared characterization according to the following experimental process. Attenuated total reflection infrared spectroscopy (ATR-FTIR) was used for analysis, and the freeze-dried complex sample was directly scanned and tested in ATR mode. For each spectrum, a total of 32 scans were accumulated, with a resolution of 4.0 cm -1 -600 em -1 . As can be seen from the figure, the coating absorption peak at around 3000 changes significantly, indicating that the hydroxyl group of the coating increases significantly, thereby increasing the hydrophilicity.

[0065] Example 7

[0066] The complex coating prepared in the above Examples 1-4 was respectively subjected to antibacterial evaluation under dynamic contact conditions (referring to the test standard ASTM E2149-2013a), and the results are shown in Table 1. As can be seen from Table 1, the CTAB as the complex coating shows more significant antibacterial performance.

[0067] Table 1

[0068] Example 1 Example 2 Example 3 Example 4 Escherichia coli 99.5％ 98.2％ 99.1％ 97.2％ Staphylococcus aureus 98.9％ 97.6％ 98.5％ 96.9％

[0069] Example 8

[0070] The composite coatings prepared in the above Examples 1-4 were respectively immersed in PBS for 10 days, and then subjected to antibacterial evaluation under dynamic contact conditions (referring to test standard ASTM E2149-2013a), and the results are shown in Table 2. As can be seen from Table 2, CTAB still showed excellent antibacterial activity after 10 days of continuous immersion, further proving that the composite coating has strong stability.

[0071] Table 2

[0072] Example 1 Example 2 Example 3 Example 4 Escherichia coli 98.2％ 97.4％ 97.9％ 96.2％ Staphylococcus aureus 97.2％ 96.4％ 96.9％ 95.8％

[0073] Example 9

[0074] The composite coatings prepared in the above Examples 1-4 were respectively subjected to biocompatibility evaluation according to the following experimental procedures.

[0075] (1) Preparation of composite coating: First, the polyurethane catheter coated with the coating in each example was cut into a circle with a diameter of 5 mm and subjected to ultraviolet irradiation for 2 h on a clean bench, and then rinsed with sterile PBS for 3 times, and the composite coating material was soaked in DMEM cell culture medium overnight for standby.

[0076] (2) According to the ISO 10993-5 standard, the cytotoxicity of the antibacterial coating of the polyurethane catheter and the antibacterial coating of the titanium alloy was studied by CCK-8 method. L929 mouse fibroblasts were cultured in a (DMEM) medium containing 10 vol% fetal bovine serum (FBS) and 1 vol% penicillin-streptomycin. In the subsequent experiment, the cells were separated from the culture bottle by adding 0.25% trypsin EDTA solution, and resuspended in fresh culture medium for 3 days. 100 μL of cells diluted to 2 x 10 4 CFU / mL were inoculated in a 96-well plate, and the polyurethane catheter to be tested and the titanium alloy substrate were placed on top of the cell layer, with three parallel samples in each group. After incubation at 37°C for 1 day, 3 days and 5 days respectively, the culture medium was removed, and then 90 μL of culture medium and 10 μL of CCK-8 solution were added to the wells. After 2 hours of culture, the absorbance of the samples was measured using a multifunctional enzyme label instrument (Switzerland TECAN M200 PRO) at a wavelength of 450 nm, and the results were expressed as a percentage relative to the control experiment. The cell survival rate was calculated using equation (2):

[0077]

[0078] The results are shown in Figure 3 . Figure 3 In the figure, the abscissa 1, 2, 3, and 4 respectively represent the data of Examples 1-4, and the cell activity of each group of composite catheters is stronger within 1, 3 days, indicating that the coating has a certain affinity to cells.

[0079] In summary, the application innovatively combines the protein and polyglutamic acid through the electrostatic self-assembly method, further applies the biological macromolecule in the medical material, and provides a related solution for the antibacterial coating on the surface of the medical instrument in practice.

Claims

1. A gamma-polyglutamic acid-quaternary ammonium salt-mussel protein coating, characterized in that, It is prepared by the following method: (1) The positively charged quaternary ammonium salt compound is dissolved in water, and after fully dissolving, mechanical stirring is carried out, and γ-polyglutamic acid clear solution is added while stirring, and after the reaction is completed, γ-polyglutamic acid-quaternary ammonium salt complex precipitate is obtained; (2) The complex precipitate obtained in step (1) is subjected to plate and frame pressure filtration, washed with water and dried; (3) The dried product obtained in step (2) is dissolved in an organic solvent with mussel protein to obtain a γ-polyglutamic acid-quaternary ammonium salt-mussel protein coating, Wherein, the γ-polyglutamic acid clear solution is prepared by the following method: 1) After diluting the γ-polyglutamic acid fermentation broth with deionized water, diatomite and pearl powder are fully mixed, then bacteria are removed by plate and frame pressure filtration, and the filtrate is recovered; 2) Add activated carbon to the filtrate obtained in step 1), mechanically stir, then recover the filtrate after plate and frame pressure filtration decolorization to obtain γ-polyglutamic acid clear solution; In step (1), the quaternary ammonium salt compound is any one of benzalkonium chloride, dodecyltrimethylammonium bromide, dodecyltrimethylammonium chloride, and cetyltrimethylammonium bromide; The mussel protein is MFP-5 type mussel protein; The yield of γ-polyglutamic acid fermentation broth is 20~40g / L, the molecular weight of γ-polyglutamic acid is 500~2000 kDa; The amount of diatomite is 1~5wt%, the amount of pearl powder is 1~5wt%, and the amount of activated carbon is 0.5~3wt%; The mass ratio of γ-polyglutamic acid to quaternary ammonium salt compound is 1:1~1:3, and the concentration of mussel protein in the final system is 250~1000 µg / mL.

2. The gamma-polyglutamic acid-quaternary ammonium salt-mussel protein coating according to claim 1, characterized in that, In step (1), the stirring rate of mechanical stirring is controlled at 200 ~ 300 rpm, and the time is 5 ~ 10 min.

3. The gamma-polyglutamic acid-quaternary ammonium salt-mussel protein coating according to claim 1, characterized in that, In step (3), the organic solvent is any one of ethanol, acetone, dichloromethane, dimethyl sulfoxide, dimethylformamide, and tetrahydrofuran, and the mass fraction of the dried product in the organic solvent is 1~10%.

4. Use of the γ-polyglutamic acid-quaternary ammonium salt-mussel protein coating of any one of claims 1-3 in the preparation of an antibacterial coating.

5. A method of preparing an antimicrobial coating on the surface of a medical device, characterized by, The γ-polyglutamic acid-quaternary ammonium salt-mussel protein coating of any one of claims 1-3 is uniformly coated on the surface of a medical device, and then dried in an oven, thereby forming a γ-polyglutamic acid-quaternary ammonium salt-mussel protein antibacterial coating on the surface of the medical device.

6. The production method according to claim 5, wherein The oven temperature is 35-40℃, and the drying time is 30~60min; The surface material of the medical device is polyurethane, polyvinyl chloride, silicone rubber, iron or titanium alloy, magnesium alloy.

7. A medical device, comprising: The surface of the medical device is coated with the γ-polyglutamic acid-quaternary ammonium salt-mussel protein coating of any one of claims 1-3.

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