Antifouling medical coating material with antibacterial function and preparation method thereof

Abstract

This invention relates to the field of medical polymer materials technology, specifically disclosing an antibacterial and antifouling medical coating material and its preparation method. The medical coating material comprises raw materials: a hydrophilic monomer, a fluorinated low surface energy monomer, an antibacterial polymer, a crosslinking agent, a photoinitiator, and a mixed solvent. The antibacterial polymer is obtained by reacting ε-polylysine sequentially with glycidyl methacrylate, 1-bromododecane, and hyaluronic acid oligomers. This invention utilizes in-situ copolymerization cured by ultraviolet light to covalently integrate the functional components into a chemically crosslinked polymer network. The resulting coating surface is highly hydrophilic, effectively resisting non-specific adhesion of proteins and bacteria. It also exhibits specific enzyme responsiveness, displaying low activity and high biocompatibility under normal physiological conditions, but being activated in a microenvironment rich in hyaluronidase caused by bacterial infection, demonstrating a highly efficient bactericidal ability exceeding 99.5% against Staphylococcus aureus and Escherichia coli.

Description

Technical Field

[0001] This invention relates to the field of medical polymer materials technology, specifically to anti-fouling medical coating materials with antibacterial functions and their preparation methods. Background Technology

[0002] Medical devices are widely used in modern clinical diagnosis and treatment, but their surfaces are highly susceptible to becoming breeding grounds for microbial adhesion and colonization, leading to medical device-related infections (DNIs). DNIs are a global health challenge, and to address this challenge, the development of functional medical coatings has become a mainstream research direction, mainly divided into two categories: antifouling coatings and antimicrobial coatings.

[0003] Antifouling coatings aim to create physical or chemical barriers that prevent the initial adhesion of biomolecules such as proteins and bacteria to the surface of medical devices. For example, this can be achieved by grafting hydrophilic polymers such as polyethylene glycol (PEG) to form a dense hydration layer, or by using fluoropolymers (such as polyfluoroalkyl silanes) to create low surface energy interfaces. However, existing single hydrophilic antifouling coatings have limited antifouling capabilities in complex bodily fluid environments, and antifouling coatings themselves do not possess bactericidal properties. When faced with high concentrations of bacterial solutions or minor defects in the coating, once bacteria adsorb and colonize, the coating will be unable to prevent the formation of subsequent biofilms, ultimately leading to the failure of its antifouling function.

[0004] Antimicrobial coatings aim to actively kill bacteria that come into contact with or are near the coating surface. Common methods include loading and releasing antimicrobial agents such as antibiotics, silver ions, and quaternary ammonium salts. These antimicrobial coatings suffer from poor specificity: firstly, the continuously released antimicrobial agents may be toxic to normal host tissue cells, affecting tissue compatibility; secondly, long-term exposure to low doses of antimicrobial agents can easily induce bacterial resistance, posing a more serious public health risk; and thirdly, the explosive release or continuous leaching of antimicrobial agents results in short-term coating functionality, making it difficult to meet the needs of long-term implantable devices. Another type is contact-killing coatings, such as immobilized quaternary ammonium salt polymers. While these avoid the problem of antimicrobial agent release, their sustained strong bactericidal activity may still damage the contacting tissue cells, resulting in poor biocompatibility. Furthermore, some existing pH-responsive charge-reversal coatings rely on anhydride hydrolysis, which is prone to non-specific activation in the slightly acidic physiological environment of the normal human body (such as in early inflammatory states), also posing a risk of tissue toxicity.

[0005] In summary, existing technologies struggle to simultaneously achieve high-efficiency antifouling properties, antibacterial properties, excellent long-term functional stability, and good biocompatibility in a single coating system. Based on the above, this invention proposes an antifouling medical coating material with antibacterial functions and a method for its preparation. Summary of the Invention

[0006] To address the challenges of achieving high-efficiency antifouling, antibacterial properties, excellent long-term functional stability, and good biocompatibility simultaneously in a single coating system using existing technologies, and the frequent occurrence of technical problems such as inducing bacterial resistance, this invention proposes an antifouling medical coating material with antibacterial function and its preparation method. The coating obtained by this invention exhibits an inert antifouling state in normal physiological environments, but its antibacterial function is specifically activated in the microenvironment of bacterial infection (rich in hyaluronidase), while also possessing excellent chemical stability and biocompatibility.

[0007] In a first aspect, the present invention provides a stain-resistant medical coating material with antibacterial function, employing the following technical solution: Antibacterial and antifouling medical coating material includes the following raw materials in parts by weight: 30-40 parts of hydrophilic monomer, 3-5 parts of fluorine-containing low surface energy monomer, 20-30 parts of antibacterial polymer, 3-5 parts of crosslinking agent, 1-3 parts of photoinitiator, and 90-150 parts of mixed solvent.

[0008] Preferably, the antibacterial polymer is obtained by reacting ε-polylysine sequentially with glycidyl methacrylate, 1-bromododecane and hyaluronic acid oligomers.

[0009] Preferably, the hydrophilic monomer is polyethylene glycol diacrylate and / or polyethylene glycol dimethacrylate.

[0010] Preferably, the fluorinated low surface energy monomer is dodecafluoroheptyl methacrylate.

[0011] Preferably, the hydrophilic monomer is obtained by mixing polyethylene glycol diacrylate and polyethylene glycol dimethacrylate in a mass ratio of 1:2-3.

[0012] Preferably, the antibacterial polymer is prepared by the following method: S1. Dissolve ε-polylysine in an aqueous solution of N,N-dimethylformamide with stirring, add glycidyl methacrylate solution dropwise under ice bath, and stir the reaction at room temperature for 15-20 h to obtain a reaction solution containing the intermediate; S2. Add 1-bromododecane to the reaction solution containing the intermediate, stir and mix, heat to 60-70℃, and reflux under nitrogen protection for 20-24 hours to obtain the quaternized polymer solution; S3. The solvent in the quaternized polymer solution is removed by rotary evaporation to obtain the quaternized polymer product. The quaternized polymer product is dissolved in deionized water, and the pH is adjusted to 8-8.5 to obtain an aqueous solution of the quaternized polymer. Hyaluronic acid oligomer, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide are dissolved in deionized water and activated for 1-2 hours to obtain an activated hyaluronic acid oligomer solution. The activated hyaluronic acid oligomer solution is added dropwise to the aqueous solution of the quaternized polymer and reacted at room temperature for 12-14 hours to obtain a reaction solution. S4. After dialysis purification of the reaction solution, freeze-dry to obtain the antibacterial polymer.

[0013] Preferably, the stirring speed in S1 is 600-800 rpm.

[0014] Preferably, the mass ratio of ε-polylysine, N,N-dimethylformamide aqueous solution and glycidyl methacrylate solution in S1 is 8-10:100:1-1.5.

[0015] Preferably, the glycidyl methacrylate solution in S1 is obtained by mixing and dissolving glycidyl methacrylate and N,N-dimethylformamide in a mass ratio of 1:12-15.

[0016] Preferably, the mass concentration of the N,N-dimethylformamide aqueous solution in S1 is 30-50%.

[0017] Preferably, the droplet acceleration rate in S1 is 0.3-0.5 mL / min.

[0018] Preferably, the mass ratio of 1-bromododecane to the reaction solution containing the intermediate in S2 is 1:25-30.

[0019] Preferably, the rotary evaporation temperature in S3 is 35-45℃ and the vacuum degree is 120-140mbar.

[0020] Preferably, the mass ratio of the quaternized polymer product to deionized water in the aqueous solution of the quaternized polymer in S3 is 1:10-15.

[0021] Preferably, the mass ratio of hyaluronic acid oligomer, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N-hydroxysuccinimide and deionized water in the hyaluronic acid oligomer activation solution in S3 is 1:0.5-0.8:0.5-0.8:10-15.

[0022] Preferably, the mass ratio of the hyaluronic acid oligomer activation solution and the quaternized polymer aqueous solution in S3 is 1:1-2.

[0023] Preferably, the molecular weight of the hyaluronic acid oligomer in S3 is 3000-5000 Da.

[0024] Preferably, the drop acceleration rate in S3 is 0.8-1 mL / min.

[0025] Preferably, in step S4, the dialysis purification is performed using a dialysis bag with a molecular weight cutoff of 3500 Da, and dialysis in deionized water for 3-5 days.

[0026] Preferably, the freeze-drying temperature in step S4 is -40 to -60°C.

[0027] Preferably, the crosslinking agent is N,N'-methylenebisacrylamide and / or ethylene glycol dimethacrylate.

[0028] Preferably, the crosslinking agent is N,N'-methylenebisacrylamide and ethylene glycol dimethacrylate in a mass ratio of 1:1-2.

[0029] Preferably, the photoinitiator is an α-hydroxy ketone compound.

[0030] Preferably, the photoinitiator is one or more of Irgacure 2959, Irgacure 1173, and Irgacure 184.

[0031] Secondly, this invention provides a method for preparing an anti-fouling medical coating material with both antibacterial and antimicrobial functions, employing the following technical solution: A method for preparing a stain-resistant medical coating material with both antibacterial and anti-fouling functions includes the following steps: Step 1: Weigh out the hydrophilic monomer, fluorinated low surface energy monomer, antibacterial polymer, crosslinking agent, photoinitiator and mixed solvent by weight and set aside. Step 2: Add the antibacterial polymer to the mixed solvent, seal and stir to obtain a homogeneous premixed solution; Step 3: While stirring, add the hydrophilic monomer, the fluorinated low surface energy monomer and the crosslinking agent, and stir for 30-50 minutes to obtain the prepolymer solution; Step 4: Under light-protected conditions, add photoinitiator to the prepolymer solution, stir for 15-30 min, and let stand at room temperature for 1-2 h to obtain the coating precursor solution. Step 5: After uniformly coating the coating precursor solution onto the surface of the medical substrate, cure it under ultraviolet light irradiation under inert gas protection, and then elute and purify it to obtain an anti-fouling medical coating with antibacterial function.

[0032] Preferably, the mixed solvent in step 2 is an ethanol solution with a mass fraction of 60-80%.

[0033] Preferably, in step 2, the sealing and stirring temperature is 40-50℃, the rotation speed is 100-200rpm, and the time is 3-5h.

[0034] Preferably, the stirring speed in step 3 is 400-600 rpm.

[0035] Preferably, the medical substrate in step 5 is a medical metal or its alloy, a medical polymer material, or a medical inorganic non-metallic material.

[0036] Preferably, the medical substrate in step 5 is an implantable polyurethane (PU) substrate.

[0037] Preferably, the coating method in step 5 is at least one of dip coating, spin coating, spray coating, or scraping coating.

[0038] Preferably, the coating amount of the precursor solution in step 5 is 20-30 mg / cm³. 2 .

[0039] Preferably, the ultraviolet irradiation in step 5 refers to using an ultraviolet lamp with a main wavelength of 365nm at a frequency of 50-150mW / cm². 2 The light intensity, irradiation for 180-300 seconds.

[0040] In summary, the present invention has the following beneficial effects: 1. This invention introduces specifically degradable hyaluronic acid oligomers as shielding groups onto an antibacterial polymer, endowing the coating with specific enzyme-responsive capabilities. Under normal physiological conditions, the shielding groups are stable, and their negative charge neutralizes the positive charge on the polymer backbone, resulting in an electrically neutral or weakly charged coating surface. This manifests as a low-activity, antifouling state. Furthermore, the use of naturally derived ε-polylysine as the polymer backbone significantly reduces the cytotoxicity of conventional cationic polymers, achieving a cell survival rate of over 96%. In the microenvironment caused by bacterial infection, hyaluronidase secreted by pathogenic bacteria (such as Staphylococcus aureus) specifically degrades the hyaluronic acid oligomers, causing the shielding groups to detach, exposing a large number of amine groups that are protonated. This significantly increases the positive charge density on the polymer surface, thereby activating its antibacterial function. The bactericidal rate against Staphylococcus aureus and Escherichia coli can exceed 99.5%. This invention's specific enzyme-triggered mechanism improves the biocompatibility of the coating material while avoiding non-specific activation under normal physiological conditions and significantly reducing the risk of inducing bacterial resistance.

[0041] 2. This invention introduces fluorinated low surface energy monomers. During the in-situ copolymerization process under UV curing, as the cross-linked network forms, fluorinated segments spontaneously accumulate on the surface, forming a "hydrophilic-hydrophobic microphase separation" structure. The dense hydration layer formed with the highly hydrophilic polyethylene glycol network as the matrix provides steric hindrance. Combined with the low surface energy barrier formed by the microphase separation region, it produces a significant synergistic antifouling effect, greatly hindering the non-specific adsorption and adhesion of biomolecules such as proteins and bacteria, thus playing an excellent synergistic physical antifouling role.

[0042] 3. This invention employs photocuring technology to integrate all functional components into a chemically cross-linked polymer network via covalent bonds, fundamentally solving the problems of easy leaching of antibacterial components and rapid functional decay in traditional coatings. Performance tests show that after immersion in simulated body fluids for 30 days, the antibacterial performance of the coating of this invention shows almost no decay, and after 500 cycles of reciprocating friction testing, the coating shows no wear or an extremely low wear rate (<0.5%), demonstrating excellent long-term functional stability and mechanical durability. Detailed Implementation

[0043] The present invention will be further described in detail below with reference to the embodiments.

[0044] For experiments not specifically described in the examples, the procedures or conditions should be followed according to the conventional experimental procedures described in the literature in this field. Reagents or instruments whose manufacturers are not specified are all commercially available conventional reagent products.

[0045] The key raw materials used in this invention are sourced from the following sources: Polyethylene glycol diacrylate: Part number 729094-1G, purchased from MeRck; Polyethylene glycol dimethacrylate: Product number P132873, purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.; Dodecafluoroheptyl methacrylate: CAS No. 2261-99-6, purchased from Hubei Xingyan New Material Technology Co., Ltd.; ε-Polylysine: CAS No. 28211-04-3, Model LBW-567, purchased from Hubei Langbowan Biomedical Co., Ltd.; Glycidyl methacrylate: CAS No. 106-91-2, purchased from Jinan Huijinchuan Chemical Co., Ltd.; 1-Bromododecane: Product No. Y36758, purchased from Shanghai Yuanye Biotechnology Co., Ltd.; Hyaluronic acid oligomer: molecular weight 3431.8 Da, catalog number ZCR-HA-18, purchased from Shanghai Zhenzhun Biotechnology Co., Ltd. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride: CAS No. 25952-53-8, purchased from Wuhan Smike Biotechnology Co., Ltd.; N-hydroxysuccinimide: CAS No. 6066-82-6, purchased from Wuhan Huaxiang Kejie Biotechnology Co., Ltd.; N,N'-Methylenebisacrylamide: CAS No. 110-26-9, purchased from Shandong Guanchang Chemical Technology Co., Ltd.; Ethylene glycol dimethacrylate: CAS No. 97-90-5, purchased from Shanghai Maclean Biochemical Technology Co., Ltd.; Irgacure2959: CAS No. 106797-53-9, purchased from Invevo Chemical Technology (Guangzhou) Co., Ltd.; Hyaluronidase: CAS No. 37326-33-3, Product No. S10060, purchased from Shanghai Yuanye Biotechnology Co., Ltd.; Staphylococcus aureus subsp. Aureus ATCC25923, catalog number 0360P, purchased from China Industrial Microbial Culture Collection Center; Escherichia coli ATCC 25922, catalog number 0335P, purchased from China Industrial Microbial Culture Collection Center; L929 mouse fibroblasts: Model CM0038, Product specification 1×10 6 CFU / mL, purchased from Shanghai Yuchun Biotechnology Co., Ltd.; Micro BCA Protein Quantitative Detection Kit: Brand Thermo Fisher Scientific Pierce, Product No. 23235, purchased from Shanghai Xiyan Scientific Instruments Co., Ltd.

[0046] Preparation Examples 1-3 and Comparative Preparation Examples 1-2 provide a method for preparing an antibacterial polymer.

[0047] Preparation Example 1 The antibacterial polymer is prepared by the following method: S1. The mass ratio of ε-polylysine, N,N-dimethylformamide aqueous solution, and glycidyl methacrylate solution was controlled at 8:100:1. The stirring speed was 600 rpm and the dropping rate was 0.3 mL / min. ε-polylysine was dissolved in 30% N,N-dimethylformamide aqueous solution and cooled in an ice-water bath. The stirring was kept constant. Glycidyl methacrylate solution (obtained by mixing and dissolving glycidyl methacrylate and N,N-dimethylformamide in a mass ratio of 1:12) was added dropwise under ice-water bath conditions. After the addition was completed, the ice bath was removed and the reaction was continuously stirred at room temperature (25℃) for 24 h to obtain a reaction solution containing intermediates. S2. Control the mass ratio of 1-bromododecane to the reaction solution containing the intermediate to 1:25, keep the stirring speed constant, add 1-bromododecane to the reaction solution containing the intermediate and stir for 20 min, then heat to 60℃ and reflux for 24 h under nitrogen protection to obtain the quaternized polymer solution. S3. After cooling the quaternized polymer solution to room temperature, the solvent was removed by rotary evaporation at 35°C and a vacuum of 140 mbar to obtain the quaternized polymer product. The quaternized polymer product was dissolved in deionized water (the mass ratio of the quaternized polymer product to deionized water was 1:10), and the pH was adjusted to 8 using 0.1 M sodium hydroxide solution to obtain an aqueous solution of the quaternized polymer. Hyaluronic acid oligomer, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide were dissolved in deionized water at a mass ratio of 1:0.5:0.8:10 and activated for 1 h to obtain an activated hyaluronic acid oligomer solution. The mass ratio of the activated hyaluronic acid oligomer solution to the aqueous solution of the quaternized polymer was controlled at 1:1. The activated hyaluronic acid oligomer solution was added dropwise to the aqueous solution of the quaternized polymer at a dropping rate of 0.8 mL / min, and the reaction was carried out at room temperature for 12 h to obtain the reaction solution. S4. The reaction solution was placed into a dialysis bag with a molecular weight cutoff of 3500 Da and purified by dialysis in deionized water for 3 days (changing the water 3 times a day). Then it was transferred to a freeze dryer and freeze-dried at -50°C to constant weight to obtain the antibacterial polymer.

[0048] Preparation Example 2 The antibacterial polymer is prepared by the following method: S1. The mass ratio of ε-polylysine, N,N-dimethylformamide aqueous solution, and glycidyl methacrylate solution was controlled at 9:100:1.2, the stirring speed was 700 rpm, and the dropping rate was 0.4 mL / min. ε-polylysine was dissolved in 40% N,N-dimethylformamide aqueous solution by stirring, and the solution was placed in an ice-water bath for cooling. The stirring was kept constant, and glycidyl methacrylate solution (obtained by mixing and dissolving glycidyl methacrylate and N,N-dimethylformamide in a mass ratio of 1:13.5) was added dropwise under ice-water bath conditions. After the addition was completed, the ice bath was removed, and the reaction was continuously stirred at room temperature (25℃) for 22 h to obtain a reaction solution containing intermediates. S2. Control the mass ratio of 1-bromododecane to the reaction solution containing the intermediate to 1:28, keep the stirring speed constant, add 1-bromododecane to the reaction solution containing the intermediate and stir for 15 min, then heat to 65℃ and reflux for 22 h under nitrogen protection to obtain the quaternized polymer solution. S3. After cooling the quaternized polymer solution to room temperature, the solvent was removed by rotary evaporation at 40℃ and a vacuum of 130mbar to obtain the quaternized polymer product. The quaternized polymer product was dissolved in deionized water (the mass ratio of the quaternized polymer product to deionized water was 1:12.5), and the pH was adjusted to 8.2 with 0.1M sodium hydroxide solution to obtain an aqueous solution of the quaternized polymer. Hyaluronic acid oligomer, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide were dissolved in deionized water at a mass ratio of 1:0.6:0.7:12.5 and activated for 1.5h to obtain an activated hyaluronic acid oligomer solution. The mass ratio of the activated hyaluronic acid oligomer solution to the aqueous solution of the quaternized polymer was controlled at 1:1.5. The activated hyaluronic acid oligomer solution was added dropwise to the aqueous solution of the quaternized polymer at a dropping rate of 0.9mL / min, and the reaction was carried out at room temperature for 13h to obtain a reaction solution. S4. The reaction solution was placed in a dialysis bag with a molecular weight cutoff of 3500 Da and purified by dialysis in deionized water for 4 days (changing the water 3 times a day). Then it was transferred to a freeze dryer and freeze-dried at -50°C to constant weight to obtain the antibacterial polymer.

[0049] Preparation Example 3 The antibacterial polymer is prepared by the following method: S1. The mass ratio of ε-polylysine, N,N-dimethylformamide aqueous solution and glycidyl methacrylate solution was controlled at 10:100:1.5, the stirring speed was 800 rpm, and the dropping rate was 0.5 mL / min. ε-polylysine was dissolved in 50% N,N-dimethylformamide aqueous solution by stirring, and the solution was placed in an ice-water bath for cooling. The stirring was kept constant, and glycidyl methacrylate solution (obtained by mixing and dissolving glycidyl methacrylate and N,N-dimethylformamide in a mass ratio of 1:15) was added dropwise under ice-water bath conditions. After the addition was completed, the ice bath was removed, and the reaction was continuously stirred at room temperature (25℃) for 20 h to obtain a reaction solution containing intermediates. S2. Control the mass ratio of 1-bromododecane to the reaction solution containing the intermediate to 1:30, keep the stirring speed constant, add 1-bromododecane to the reaction solution containing the intermediate and stir for 10 min, then heat to 70℃ and reflux for 20 h under nitrogen protection to obtain the quaternized polymer solution. S3. After cooling the quaternized polymer solution to room temperature, the solvent was removed by rotary evaporation at 45°C and 120 mbar to obtain the quaternized polymer product. The quaternized polymer product was dissolved in deionized water (mass ratio of quaternized polymer product to deionized water was 1:15), and the pH was adjusted to 8.5 using 0.1 M sodium hydroxide solution to obtain an aqueous solution of quaternized polymer. Hyaluronic acid oligomer, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide were dissolved in deionized water at a mass ratio of 1:0.8:0.5:15 and activated for 2 h to obtain an activated hyaluronic acid oligomer solution. The mass ratio of the activated hyaluronic acid oligomer solution to the aqueous solution of quaternized polymer was controlled at 1:2. The activated hyaluronic acid oligomer solution was added dropwise to the aqueous solution of quaternized polymer at a dropping rate of 1 mL / min. The reaction was carried out at room temperature for 14 h to obtain the reaction solution. S4. The reaction solution was placed in a dialysis bag with a molecular weight cutoff of 3500 Da and purified by dialysis in deionized water for 5 days (changing the water 3 times a day). Then it was transferred to a freeze dryer and freeze-dried at -50°C to constant weight to obtain the antibacterial polymer.

[0050] Comparative Preparation Example 1 Compare with Preparation Example 1. The preparation is the same as Preparation Example 1, except that step S3 is omitted, as detailed below: The antibacterial polymer is prepared by the following method: S1. The mass ratio of ε-polylysine, N,N-dimethylformamide aqueous solution, and glycidyl methacrylate solution was controlled at 8:100:1. The stirring speed was 600 rpm and the dropping rate was 0.3 mL / min. ε-polylysine was dissolved in 30% N,N-dimethylformamide aqueous solution and cooled in an ice-water bath. The stirring was kept constant. Glycidyl methacrylate solution (obtained by mixing and dissolving glycidyl methacrylate and N,N-dimethylformamide in a mass ratio of 1:12) was added dropwise under ice-water bath conditions. After the addition was completed, the ice bath was removed and the reaction was continuously stirred at room temperature (25℃) for 24 h to obtain a reaction solution containing intermediates. S2. Control the mass ratio of 1-bromododecane to the reaction solution containing the intermediate to 1:25, keep the stirring speed constant, add 1-bromododecane to the reaction solution containing the intermediate and stir for 20 min, then heat to 60℃ and reflux for 24 h under nitrogen protection to obtain the quaternized polymer solution. S3. After cooling the quaternized polymer solution to room temperature, the solvent was removed by rotary evaporation at 45°C and 120 mbar to obtain the quaternized polymer product. The quaternized polymer product was dissolved in anhydrous ethanol at 6 times its mass to obtain a quaternized polymer product solution. The quaternized polymer product solution was added dropwise to diethyl ether at 10 times its volume to precipitate and purify. After repeated purification 3 times, the product was collected by vacuum filtration under reduced pressure and dried under vacuum at 40°C to constant weight to obtain the antibacterial polymer.

[0051] Comparative Preparation Example 2 Comparing Preparation Example 2 with Preparation Example 1, the only difference is that the reaction with glycidyl methacrylate in the original step S1 is omitted. The specific details are as follows: The antibacterial polymer is prepared by the following method: S1. Control the mass ratio of ε-polylysine and N,N-dimethylformamide to 8:100, and the stirring speed to 600 rpm. Dissolve ε-polylysine in a 30% N,N-dimethylformamide aqueous solution to obtain a reaction solution. S2. Control the mass ratio of 1-bromododecane to the reaction solution to 1:25, keep the stirring speed constant, add 1-bromododecane to the reaction solution and stir for 20 min, then heat to 60℃ and reflux for 24 h under nitrogen protection to obtain the quaternization reaction solution; S3. After cooling the quaternized polymer solution to room temperature, the solvent was removed by rotary evaporation at 35°C and a vacuum of 140 mbar to obtain the quaternized polymer product. The quaternized polymer product was dissolved in deionized water (the mass ratio of the quaternized polymer product to deionized water was 1:10), and the pH was adjusted to 8 using 0.1 M sodium hydroxide solution to obtain an aqueous solution of the quaternized polymer. Hyaluronic acid oligomer, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide were dissolved in deionized water at a mass ratio of 1:0.5:0.8:10 and activated for 1 h to obtain an activated hyaluronic acid oligomer solution. The mass ratio of the activated hyaluronic acid oligomer solution to the aqueous solution of the quaternized polymer was controlled at 1:1. The activated hyaluronic acid oligomer solution was added dropwise to the aqueous solution of the quaternized polymer at a dropping rate of 0.8 mL / min, and the reaction was carried out at room temperature for 12 h to obtain the reaction solution. S4. The reaction solution was placed into a dialysis bag with a molecular weight cutoff of 3500 Da and purified by dialysis in deionized water for 3 days (changing the water 3 times a day). Then it was transferred to a freeze dryer and freeze-dried at -50°C to constant weight to obtain the antibacterial polymer.

[0052] Examples 1-3 provide anti-fouling medical coating materials with antibacterial function and their preparation methods.

[0053] Example 1 The antibacterial and antifouling medical coating material comprises the following raw materials in parts by weight: 30 parts hydrophilic monomer, 3 parts fluorine-containing low surface energy monomer, 20 parts antibacterial polymer, 3 parts crosslinking agent, 1 part photoinitiator, and 90 parts mixed solvent.

[0054] The hydrophilic monomers are polyethylene glycol diacrylate and polyethylene glycol dimethacrylate in a mass ratio of 1:2; the fluorinated low surface energy monomer is dodecafluoroheptyl methacrylate; the antibacterial polymer is prepared by Preparation Example 1; the crosslinking agent is N,N'-methylenebisacrylamide and ethylene glycol dimethacrylate in a mass ratio of 1:1; the photoinitiator is Irgacure 2959; and the mixed solvent is a 60% ethanol solution.

[0055] A method for preparing a stain-resistant medical coating material with both antibacterial and anti-fouling functions includes the following steps: Step 1: Weigh out the hydrophilic monomer, fluorinated low surface energy monomer, antibacterial polymer, crosslinking agent, photoinitiator and mixed solvent by weight and set aside. Step 2: Add the antibacterial polymer to the mixed solvent. Under sealed conditions, control the stirring temperature at 40℃ and the stirring speed at 200rpm for 3 hours to obtain a uniform premixed solution. Step 3: Control the stirring speed to 400 rpm. While stirring, add the hydrophilic monomer, the fluorinated low surface energy monomer and the crosslinking agent to the premixed solution and stir for 50 min to obtain the prepolymer solution. Step 4: Under light-protected conditions, add photoinitiator to the prepolymer solution, stir for 15 min, and let stand at room temperature for 1 h to obtain the coating precursor solution. Step 5: Take a clean implantable polyurethane (PU) substrate and control the coating amount to 20 mg / cm³. 2 After the coating precursor solution was uniformly coated onto the substrate surface using spin coating, it was placed in a UV curing machine and cured under nitrogen protection using a 365nm UV lamp at 50mW / cm². 2 After irradiation with light intensity for 180 seconds to achieve complete cross-linking and curing, the coated substrate was sequentially placed in deionized water and 75% ethanol solution, and ultrasonically cleaned three times each for 15 minutes at room temperature to thoroughly remove unreacted monomers, cross-linking agents, and photoinitiator residues. Following washing, the substrate was vacuum-dried to constant weight at 50°C under aseptic conditions to obtain an antibacterial and anti-fouling medical coating.

[0056] Example 2 The antibacterial and antifouling medical coating material comprises the following raw materials in parts by weight: 35 parts hydrophilic monomer, 4 parts fluorine-containing low surface energy monomer, 25 parts antibacterial polymer, 4 parts crosslinking agent, 2 parts photoinitiator, and 120 parts mixed solvent.

[0057] The hydrophilic monomers are polyethylene glycol diacrylate and polyethylene glycol dimethacrylate in a mass ratio of 1:2.5; the fluorinated low surface energy monomer is dodecafluoroheptyl methacrylate; the antibacterial polymer is prepared by Preparation Example 2; the crosslinking agent is N,N'-methylenebisacrylamide and ethylene glycol dimethacrylate in a mass ratio of 1:1.5; the photoinitiator is Irgacure 2959; and the mixed solvent is a 70% ethanol solution.

[0058] A method for preparing a stain-resistant medical coating material with both antibacterial and anti-fouling functions includes the following steps: Step 1: Weigh out the hydrophilic monomer, fluorinated low surface energy monomer, antibacterial polymer, crosslinking agent, photoinitiator and mixed solvent by weight and set aside. Step 2: Add the antibacterial polymer to the mixed solvent. Under sealed conditions, control the stirring temperature at 45℃ and the stirring speed at 150 rpm for 4 hours to obtain a uniform premixed solution. Step 3: Control the stirring speed to 500 rpm. While stirring, add the hydrophilic monomer, the fluorinated low surface energy monomer and the crosslinking agent to the premixed solution, and continue stirring for 40 min to obtain the prepolymer solution. Step 4: Under light-protected conditions, add photoinitiator to the prepolymer solution, stir for 25 min, and let stand at room temperature for 1.5 h to obtain the coating precursor solution. Step 5: Take a clean implantable polyurethane (PU) substrate and control the coating amount to 25 mg / cm³. 2 After the coating precursor solution was uniformly coated onto the substrate surface using spin coating, it was placed in a UV curing machine and cured under nitrogen protection using a 365nm UV lamp at 100mW / cm². 2 After irradiation with light intensity for 240 s to achieve complete cross-linking and curing, the coated substrate was sequentially placed in deionized water and 75% ethanol solution, and ultrasonically cleaned three times each at room temperature for 18 minutes each time to thoroughly remove unreacted monomers, cross-linking agents, and photoinitiator residues. After washing, the substrate was vacuum dried to constant weight at 50°C under aseptic conditions to obtain an antibacterial and anti-fouling medical coating.

[0059] Example 3 The antibacterial and antifouling medical coating material comprises the following raw materials in parts by weight: 40 parts hydrophilic monomer, 5 parts fluorine-containing low surface energy monomer, 30 parts antibacterial polymer, 5 parts crosslinking agent, 3 parts photoinitiator, and 150 parts mixed solvent.

[0060] The hydrophilic monomers are polyethylene glycol diacrylate and polyethylene glycol dimethacrylate in a mass ratio of 1:3; the fluorinated low surface energy monomer is dodecafluoroheptyl methacrylate; the antibacterial polymer is prepared by Preparation Example 3; the crosslinking agent is N,N'-methylenebisacrylamide and ethylene glycol dimethacrylate in a mass ratio of 1:2; the photoinitiator is Irgacure 2959; and the mixed solvent is an 80% ethanol solution.

[0061] A method for preparing a stain-resistant medical coating material with both antibacterial and anti-fouling functions includes the following steps: Step 1: Weigh out the hydrophilic monomer, fluorinated low surface energy monomer, antibacterial polymer, crosslinking agent, photoinitiator and mixed solvent by weight and set aside. Step 2: Add the antibacterial polymer to the mixed solvent. Under sealed conditions, control the stirring temperature at 50℃ and the stirring speed at 100 rpm for 5 hours to obtain a uniform premixed solution. Step 3: Control the stirring speed to 600 rpm. While stirring, add the hydrophilic monomer, the fluorinated low surface energy monomer and the crosslinking agent to the premixed solution, and continue stirring for 30 min to obtain the prepolymer solution. Step 4: Under light-protected conditions, add photoinitiator to the prepolymer solution, stir for 30 min, and let stand at room temperature for 2 h to obtain the coating precursor solution. Step 5: Take a clean implantable polyurethane (PU) substrate and control the coating amount to 30 mg / cm³. 2 After the coating precursor solution was uniformly coated onto the substrate surface using spin coating, it was placed in a UV curing machine and cured under nitrogen protection using a 365nm UV lamp at 150mW / cm². 2 After irradiation with light intensity for 300 s to achieve complete cross-linking and curing, the coated substrate was sequentially placed in deionized water and 75% ethanol solution, and ultrasonically cleaned three times each for 20 min at room temperature to thoroughly remove unreacted monomers, cross-linking agents, and photoinitiator residues. Following washing, the substrate was vacuum dried to constant weight at 50°C under aseptic conditions to obtain an antibacterial and anti-fouling medical coating.

[0062] To verify the comprehensive performance of the antibacterial and antifouling medical coating material provided by the present invention, comparative examples 1-6 were set up, wherein: Comparative Example 1 Comparative Example 1 is the same as Example 1, except that the antibacterial polymer prepared in Preparation Example 1 is replaced with the antibacterial polymer prepared in Comparative Preparation Example 1. Specifically: The antibacterial and antifouling medical coating material comprises the following raw materials in parts by weight: 30 parts hydrophilic monomer, 3 parts fluorine-containing low surface energy monomer, 20 parts antibacterial polymer, 3 parts crosslinking agent, 1 part photoinitiator, and 90 parts mixed solvent.

[0063] The hydrophilic monomers are polyethylene glycol diacrylate and polyethylene glycol dimethacrylate in a mass ratio of 1:2; the fluorinated low surface energy monomer is dodecafluoroheptyl methacrylate; the antibacterial polymer was prepared by Comparative Preparation Example 1; the crosslinking agent is N,N'-methylenebisacrylamide and ethylene glycol dimethacrylate in a mass ratio of 1:1; the photoinitiator is Irgacure 2959; and the mixed solvent is a 60% ethanol solution.

[0064] A method for preparing a stain-resistant medical coating material with both antibacterial and anti-fouling functions includes the following steps: Step 1: Weigh out the hydrophilic monomer, fluorinated low surface energy monomer, antibacterial polymer, crosslinking agent, photoinitiator and mixed solvent by weight and set aside. Step 2: Add the antibacterial polymer to the mixed solvent. Under sealed conditions, control the stirring temperature at 40℃ and the stirring speed at 200rpm for 3 hours to obtain a uniform premixed solution. Step 3: Control the stirring speed to 400 rpm. While stirring, add the hydrophilic monomer, the fluorinated low surface energy monomer and the crosslinking agent to the premixed solution and stir for 50 min to obtain the prepolymer solution. Step 4: Under light-protected conditions, add photoinitiator to the prepolymer solution, stir for 15 min, and let stand at room temperature for 1 h to obtain the coating precursor solution. Step 5: Take a clean implantable polyurethane (PU) substrate and control the coating amount to 20 mg / cm³. 2 After the coating precursor solution was uniformly coated onto the substrate surface using spin coating, it was placed in a UV curing machine and cured under nitrogen protection using a 365nm UV lamp at 50mW / cm². 2 After irradiation with light intensity for 180 seconds to achieve complete cross-linking and curing, the coated substrate was sequentially placed in deionized water and 75% ethanol solution, and ultrasonically cleaned three times each for 15 minutes at room temperature to thoroughly remove unreacted monomers, cross-linking agents, and photoinitiator residues. Following washing, the substrate was vacuum-dried to constant weight at 50°C under aseptic conditions to obtain an antibacterial and anti-fouling medical coating.

[0065] Comparative Example 2 Comparative Example 2 is the same as Example 1, except that the antibacterial polymer prepared in Preparation Example 1 is replaced with the antibacterial polymer prepared in Comparative Preparation Example 2. Specifically: The antibacterial and antifouling medical coating material comprises the following raw materials in parts by weight: 30 parts hydrophilic monomer, 3 parts fluorine-containing low surface energy monomer, 20 parts antibacterial polymer, 3 parts crosslinking agent, 1 part photoinitiator, and 90 parts mixed solvent.

[0066] The hydrophilic monomers were polyethylene glycol diacrylate and polyethylene glycol dimethacrylate in a mass ratio of 1:2; the fluorinated low surface energy monomer was dodecafluoroheptyl methacrylate; the antibacterial polymer was prepared by Comparative Preparation Example 2; the crosslinking agent was N,N'-methylenebisacrylamide and ethylene glycol dimethacrylate in a mass ratio of 1:1; the photoinitiator was Irgacure 2959; and the mixed solvent was a 60% ethanol solution.

[0067] A method for preparing a stain-resistant medical coating material with both antibacterial and anti-fouling functions includes the following steps: Step 1: Weigh out the hydrophilic monomer, fluorinated low surface energy monomer, antibacterial polymer, crosslinking agent, photoinitiator and mixed solvent by weight and set aside. Step 2: Add the antibacterial polymer to the mixed solvent. Under sealed conditions, control the stirring temperature at 40℃ and the stirring speed at 200rpm for 3 hours to obtain a uniform premixed solution. Step 3: Control the stirring speed to 400 rpm. While stirring, add the hydrophilic monomer, the fluorinated low surface energy monomer and the crosslinking agent to the premixed solution and stir for 50 min to obtain the prepolymer solution. Step 4: Under light-protected conditions, add photoinitiator to the prepolymer solution, stir for 15 min, and let stand at room temperature for 1 h to obtain the coating precursor solution. Step 5: Take a clean implantable polyurethane (PU) substrate and control the coating amount to 20 mg / cm³. 2 After the coating precursor solution was uniformly coated onto the substrate surface using spin coating, it was placed in a UV curing machine and cured under nitrogen protection using a 365nm UV lamp at 50mW / cm². 2 After irradiation with light intensity for 180 seconds to achieve complete cross-linking and curing, the coated substrate was sequentially placed in deionized water and 75% ethanol solution, and ultrasonically cleaned three times each for 15 minutes at room temperature to thoroughly remove unreacted monomers, cross-linking agents, and photoinitiator residues. Following washing, the substrate was vacuum-dried to constant weight at 50°C under aseptic conditions to obtain an antibacterial and anti-fouling medical coating.

[0068] Comparative Example 3 Comparative Example 3 is the same as Example 1, except that the antibacterial polymer is ε-polylysine. Details are as follows: The antibacterial and antifouling medical coating material comprises the following raw materials in parts by weight: 30 parts hydrophilic monomer, 3 parts fluorine-containing low surface energy monomer, 20 parts antibacterial polymer, 3 parts crosslinking agent, 1 part photoinitiator, and 90 parts mixed solvent.

[0069] The hydrophilic monomers are polyethylene glycol diacrylate and polyethylene glycol dimethacrylate in a mass ratio of 1:2; the fluorinated low surface energy monomer is dodecafluoroheptyl methacrylate; the antibacterial polymer is ε-polylysine; the crosslinking agent is N,N'-methylenebisacrylamide and ethylene glycol dimethacrylate in a mass ratio of 1:1; the photoinitiator is Irgacure 2959; and the mixed solvent is a 60% ethanol solution.

[0070] A method for preparing a stain-resistant medical coating material with both antibacterial and anti-fouling functions includes the following steps: Step 1: Weigh out the hydrophilic monomer, fluorinated low surface energy monomer, antibacterial polymer, crosslinking agent, photoinitiator and mixed solvent by weight and set aside. Step 2: Add the antibacterial polymer to the mixed solvent. Under sealed conditions, control the stirring temperature at 40℃ and the stirring speed at 200rpm for 3 hours to obtain a uniform premixed solution. Step 3: Control the stirring speed to 400 rpm. While stirring, add the hydrophilic monomer, the fluorinated low surface energy monomer and the crosslinking agent to the premixed solution and stir for 50 min to obtain the prepolymer solution. Step 4: Under light-protected conditions, add photoinitiator to the prepolymer solution, stir for 15 min, and let stand at room temperature for 1 h to obtain the coating precursor solution. Step 5: Take a clean implantable polyurethane (PU) substrate and control the coating amount to 20 mg / cm³. 2 After the coating precursor solution was uniformly coated onto the substrate surface using spin coating, it was placed in a UV curing machine and cured under nitrogen protection using a 365nm UV lamp at 50mW / cm². 2 After irradiation with light intensity for 180 seconds to achieve complete cross-linking and curing, the coated substrate was sequentially placed in deionized water and 75% ethanol solution, and ultrasonically cleaned three times each for 15 minutes at room temperature to thoroughly remove unreacted monomers, cross-linking agents, and photoinitiator residues. Following washing, the substrate was vacuum-dried to constant weight at 50°C under aseptic conditions to obtain an antibacterial and anti-fouling medical coating.

[0071] Comparative Example 4 Comparative Example 4 is the same as Example 1, except that the crosslinking agent is only N,N'-methylenebisacrylamide. Specifically: The antibacterial and antifouling medical coating material comprises the following raw materials in parts by weight: 30 parts hydrophilic monomer, 3 parts fluorine-containing low surface energy monomer, 20 parts antibacterial polymer, 3 parts crosslinking agent, 1 part photoinitiator, and 90 parts mixed solvent.

[0072] The hydrophilic monomers are polyethylene glycol diacrylate and polyethylene glycol dimethacrylate in a mass ratio of 1:2; the fluorinated low surface energy monomer is dodecafluoroheptyl methacrylate; the antibacterial polymer is prepared by Preparation Example 1; the crosslinking agent is N,N'-methylenebisacrylamide; the photoinitiator is Irgacure 2959; and the mixed solvent is a 60% ethanol solution.

[0073] A method for preparing a stain-resistant medical coating material with both antibacterial and anti-fouling functions includes the following steps: Step 1: Weigh out the hydrophilic monomer, fluorinated low surface energy monomer, antibacterial polymer, crosslinking agent, photoinitiator and mixed solvent by weight and set aside. Step 2: Add the antibacterial polymer to the mixed solvent. Under sealed conditions, control the stirring temperature at 40℃ and the stirring speed at 200rpm for 3 hours to obtain a uniform premixed solution. Step 3: Control the stirring speed to 400 rpm. While stirring, add the hydrophilic monomer, the fluorinated low surface energy monomer and the crosslinking agent to the premixed solution and stir for 50 min to obtain the prepolymer solution. Step 4: Under light-protected conditions, add photoinitiator to the prepolymer solution, stir for 15 min, and let stand at room temperature for 1 h to obtain the coating precursor solution. Step 5: Take a clean implantable polyurethane (PU) substrate and control the coating amount to 20 mg / cm³. 2 After the coating precursor solution was uniformly coated onto the substrate surface using spin coating, it was placed in a UV curing machine and cured under nitrogen protection using a 365nm UV lamp at 50mW / cm². 2 After irradiation with light intensity for 180 seconds to achieve complete cross-linking and curing, the coated substrate was sequentially placed in deionized water and 75% ethanol solution, and ultrasonically cleaned three times each for 15 minutes at room temperature to thoroughly remove unreacted monomers, cross-linking agents, and photoinitiator residues. Following washing, the substrate was vacuum-dried to constant weight at 50°C under aseptic conditions to obtain an antibacterial and anti-fouling medical coating.

[0074] Comparative Example 5 Comparative Example 5 is the same as Example 1, except that the crosslinking agent is only ethylene glycol dimethacrylate. Specifically: The antibacterial and antifouling medical coating material comprises the following raw materials in parts by weight: 30 parts hydrophilic monomer, 3 parts fluorine-containing low surface energy monomer, 20 parts antibacterial polymer, 3 parts crosslinking agent, 1 part photoinitiator, and 90 parts mixed solvent.

[0075] The hydrophilic monomers are polyethylene glycol diacrylate and polyethylene glycol dimethacrylate in a mass ratio of 1:2; the fluorinated low surface energy monomer is dodecafluoroheptyl methacrylate; the antibacterial polymer is prepared by Preparation Example 1; the crosslinking agent is ethylene glycol dimethacrylate; the photoinitiator is Irgacure 2959; and the mixed solvent is a 60% ethanol solution.

[0076] A method for preparing a stain-resistant medical coating material with both antibacterial and anti-fouling functions includes the following steps: Step 1: Weigh out the hydrophilic monomer, fluorinated low surface energy monomer, antibacterial polymer, crosslinking agent, photoinitiator and mixed solvent by weight and set aside. Step 2: Add the antibacterial polymer to the mixed solvent. Under sealed conditions, control the stirring temperature at 40℃ and the stirring speed at 200rpm for 3 hours to obtain a uniform premixed solution. Step 3: Control the stirring speed to 400 rpm. While stirring, add the hydrophilic monomer, the fluorinated low surface energy monomer and the crosslinking agent to the premixed solution and stir for 50 min to obtain the prepolymer solution. Step 4: Under light-protected conditions, add photoinitiator to the prepolymer solution, stir for 15 min, and let stand at room temperature for 1 h to obtain the coating precursor solution. Step 5: Take a clean implantable polyurethane (PU) substrate and control the coating amount to 20 mg / cm³. 2 After the coating precursor solution was uniformly coated onto the substrate surface using spin coating, it was placed in a UV curing machine and cured under nitrogen protection using a 365nm UV lamp at 50mW / cm². 2 After irradiation with light intensity for 180 seconds to achieve complete cross-linking and curing, the coated substrate was sequentially placed in deionized water and 75% ethanol solution, and ultrasonically cleaned three times each for 15 minutes at room temperature to thoroughly remove unreacted monomers, cross-linking agents, and photoinitiator residues. Following washing, the substrate was vacuum-dried to constant weight at 50°C under aseptic conditions to obtain an antibacterial and anti-fouling medical coating.

[0077] Comparative Example 6 is the same as Example 1, except that the raw material formulation does not contain fluorinated low surface energy monomers. Details are as follows: The antibacterial and anti-fouling medical coating material comprises the following raw materials in parts by weight: 30 parts hydrophilic monomer, 20 parts antibacterial polymer, 3 parts crosslinking agent, 1 part photoinitiator, and 90 parts mixed solvent.

[0078] The hydrophilic monomers are polyethylene glycol diacrylate and polyethylene glycol dimethacrylate in a mass ratio of 1:2; the antibacterial polymer is prepared by Preparation Example 1; the crosslinking agent is N,N'-methylenebisacrylamide and ethylene glycol dimethacrylate in a mass ratio of 1:1; the photoinitiator is Irgacure 2959; and the mixed solvent is a 60% ethanol solution.

[0079] A method for preparing a stain-resistant medical coating material with both antibacterial and anti-fouling functions includes the following steps: Step 1: Weigh out the hydrophilic monomer, antibacterial polymer, crosslinking agent, photoinitiator and mixed solvent by weight and set aside. Step 2: Add the antibacterial polymer to the mixed solvent. Under sealed conditions, control the stirring temperature at 40℃ and the stirring speed at 200rpm for 3 hours to obtain a uniform premixed solution. Step 3: Control the stirring speed to 400 rpm, add hydrophilic monomer and crosslinking agent to the premixed solution while stirring, and stir for 50 min to obtain prepolymer solution; Step 4: Under light-protected conditions, add photoinitiator to the prepolymer solution, stir for 15 min, and let stand at room temperature for 1 h to obtain the coating precursor solution. Step 5: Take a clean implantable polyurethane (PU) substrate and control the coating amount to 20 mg / cm³. 2 After the coating precursor solution was uniformly coated onto the substrate surface using spin coating, it was placed in a UV curing machine and cured under nitrogen protection using a 365nm UV lamp at 50mW / cm². 2 After irradiation with light intensity for 180 seconds to achieve complete cross-linking and curing, the coated substrate was sequentially placed in deionized water and 75% ethanol solution, and ultrasonically cleaned three times each for 15 minutes at room temperature to thoroughly remove unreacted monomers, cross-linking agents, and photoinitiator residues. Following washing, the substrate was vacuum-dried to constant weight at 50°C under aseptic conditions to obtain an antibacterial and anti-fouling medical coating.

[0080] The comprehensive performance of the antibacterial and antifouling medical coating materials prepared in Examples 1-3 and Comparative Examples 1-6 of this invention was tested respectively.

[0081] 1. Antibacterial performance test The coating samples (1cm × 1cm) from Examples 1-3 and Comparative Examples 1-6 were placed in 24-well plates, and 1mL of bacterial suspension was added to each well, which was 1×10⁻⁶ cm. 6 CFU / mL Staphylococcus aureus (S. aureus) bacterial suspension (prepared with standard pH 7.4 PBS buffer (without enzyme) or pH 7.4 PBS buffer containing 100 U / mL hyaluronidase (HAase)) and 1×106 CFU / mL *E. coli* bacterial suspension (prepared with either standard pH 7.4 PBS buffer (without enzyme) or pH 7.4 PBS buffer containing 100 U / mL hyaluronidase (HAase)) was incubated at 37°C for 24 h on a shaker (150 rpm). The control group consisted of uncoated implantable polyurethane (PU) substrates. After incubation, the bacterial suspension was serially diluted, plated onto nutrient agar plates, and incubated at 37°C for 24 h before viable cell counts were performed. The antibacterial rate was calculated using the following formula: Antibacterial rate (%) = [(number of viable bacteria in control group - number of viable bacteria in experimental group) / number of viable bacteria in control group] × 100%.

[0082] 2. Antibacterial stability test The coating samples of Examples 1-3 and Comparative Examples 1-6 were immersed in PBS buffer (containing 100 U / mL hyaluronidase) at pH 7.4 at 37°C. The coating samples were taken out on day 1, day 15 and day 30, rinsed with sterile water and tested for their antibacterial rate against Staphylococcus aureus according to the above method.

[0083] 3. Antifouling performance test (1) Water contact angle test: The static water contact angle of the coating samples of Examples 1-3 and Comparative Examples 1-6 was measured at room temperature using a contact angle meter (DSA100). Five different locations were tested for each sample, and the average value was taken.

[0084] (2) Bacterial adhesion test: Escherichia coli was cultured in LB medium to the logarithmic growth phase, and the bacterial cells were collected by centrifugation. After washing three times with PBS buffer at pH 7.4, the cells were resuspended in PBS buffer and the bacterial concentration was adjusted to 1×10⁻⁶. 8 CFU / mL. The coated samples from Examples 1-3 and Comparative Examples 1-6 were co-incubated with *E. coli* bacterial suspension for 4 hours, rinsed with PBS buffer, stained with DAPI, and the number of adhered bacteria (CFU / mL) was observed and counted under a fluorescence microscope. 2 ).

[0085] (3) Protein Adsorption Test: The coated samples of Examples 1-3 and Comparative Examples 1-6 were immersed in bovine serum albumin (BSA, 1 mg / mL) and fibrinogen (Fg, 1 mg / mL) solutions dissolved in PBS buffer (pH=7.4) and incubated at 37°C for 2 h. After rinsing the samples with PBS buffer, 2% sodium dodecyl sulfate solution was added and sonicated to elute the adsorbed proteins. The protein concentration in the eluent was determined using the Micro BCA protein quantification kit, and the protein adsorption amount (ng / cm²) was calculated based on the sample surface area. 2 ).

[0086] 4. Mechanical stability test Using a multi-functional friction and wear testing machine (Unite MMW-1), a normal load of 10N was applied to the coating samples of Examples 1-3 and Comparative Examples 1-6, and 500 reciprocating friction tests were performed at a frequency of 1Hz. The mass (m) of the coating samples was accurately weighed before and after the test. 前 and m 后 ), calculate the wear rate of the coating.

[0087] Wear rate (%) = [(m)] 前 -m 后 ) / m 前 ] × 100%.

[0088] 5. Biocompatibility testing 100% extracts of the coating samples of Examples 1-3 and Comparative Examples 1-6 were prepared according to GB / T 16886.5-2017 "Biological evaluation of medical devices - Part 5: In vitro cytotoxicity test". The cell viability of L929 fibroblasts after co-culturing with 100% extract for 24 h was detected by CCK-8 method.

[0089] The test results are shown in Table 1-4.

[0090] Table 1. Test data on the antibacterial properties of the coating material under different microenvironments. As shown in Table 1, Examples 1-3 exhibited low antibacterial rates against Staphylococcus aureus and Escherichia coli under normal physiological conditions without enzymes, demonstrating excellent bioinertness. However, their antibacterial rates significantly increased in a microenvironment containing hyaluronidase. This demonstrates that hyaluronic acid oligomers, acting as shielding groups, can endow the coating with excellent specific enzyme-triggered activation capabilities. In contrast, Comparative Example 1, lacking hyaluronic acid shielding groups, exposed a high density of cations, exhibiting extremely high bactericidal activity in both environments but losing environmental responsiveness. Comparative Example 3, using unquaternized ordinary ε-polylysine, lacked potent antibacterial groups, resulting in a significantly lower activation antibacterial rate in an enzyme-containing environment compared to Example 1.

[0091] Table 2 Test data on the antibacterial stability of the coating materials As shown in Table 2, after immersion in enzyme-containing simulated body fluids for up to 30 days, the antibacterial rate of Examples 1-3 remained stable at over 99.5%, with virtually no significant attenuation. This demonstrates that the photocuring in-situ copolymerization technology firmly anchors the antibacterial polymer within the coating network, achieving excellent long-term stability. In contrast, Comparative Example 2, because its antibacterial polymer lacked glycidyl methacrylate to provide cross-linking double bonds, could not covalently bond with the matrix network. This resulted in the core antibacterial component being easily eluted and lost during immersion, leading to a sharp drop in the antibacterial rate after 30 days.

[0092] Table 3. Data on the antifouling performance of coating materials As shown in Table 3, Examples 1-3 possess moderate surface hydrophilicity and exhibit excellent antifouling performance in bacterial adhesion and protein adsorption tests. Comparative Example 1, lacking hyaluronic acid shielding groups, shows significantly deteriorated antifouling performance due to the large-scale adsorption of negatively charged proteins and bacteria by exposed high-density quaternary ammonium cations via electrostatic attraction. Comparative Example 6, lacking fluorinated low-surface-energy monomers, cannot construct a microphase separation barrier, resulting in severely impaired surface resistance to non-specific protein adsorption.

[0093] Table 4. Test data on mechanical stability and biocompatibility of coating materials As shown in Table 4, Examples 1-3 exhibited extremely low wear rates, and the survival rate of L929 fibroblasts was greater than 97%, demonstrating excellent mechanical stability and biocompatibility. Comparative Example 1, lacking the masking effect of hyaluronic acid, exhibited a high cationic charge over a long period, showing strong non-specific toxicity to normal cells, significantly reducing cell survival rate, and posing a high risk for clinical application. Comparative Example 2, due to the failure to achieve covalent graft crosslinking, had a loose coating network structure and poor cohesion, leading to severe peeling during friction cycles and a high wear rate. Comparative Examples 4 and 5, using a single crosslinking agent, also failed to form a strong and compact polymer network, resulting in varying degrees of decrease in mechanical wear resistance.

[0094] This specific embodiment is merely an explanation of the present invention and is not intended to limit the invention. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they are within the scope of the claims of the present invention.

Claims

1. An anti-fouling medical coating material having an antibacterial function, characterized by, The raw materials include the following parts by weight: 30-40 parts of hydrophilic monomer, 3-5 parts of fluorine-containing low surface energy monomer, 20-30 parts of antibacterial polymer, 3-5 parts of crosslinking agent, 1-3 parts of photoinitiator and 90-150 parts of mixed solvent; The antibacterial polymer was obtained by reacting ε-polylysine sequentially with glycidyl methacrylate, 1-bromododecane, and hyaluronic acid oligomers.

2. The anti-fouling medical coating material with antibacterial function according to claim 1, characterized in that, The hydrophilic monomer is polyethylene glycol diacrylate and / or polyethylene glycol dimethacrylate.

3. The anti-fouling medical coating material with antibacterial function according to claim 1, characterized in that, The antibacterial polymer is prepared by the following method: S1. Dissolve ε-polylysine in an aqueous solution of N,N-dimethylformamide with stirring, add glycidyl methacrylate solution dropwise under ice bath, and stir the reaction at room temperature for 15-20 h to obtain a reaction solution containing the intermediate; S2. Add 1-bromododecane to the reaction solution containing the intermediate, stir and mix, heat to 60-70℃, and reflux under nitrogen protection for 20-24 hours to obtain the quaternized polymer solution; S3. The solvent in the quaternized polymer solution is removed by rotary evaporation to obtain the quaternized polymer product. The quaternized polymer product is dissolved in deionized water, and the pH is adjusted to 8-8.5 to obtain an aqueous solution of the quaternized polymer. Hyaluronic acid oligomer, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide are dissolved in deionized water and activated for 1-2 hours to obtain an activated hyaluronic acid oligomer solution. The activated hyaluronic acid oligomer solution is added dropwise to the aqueous solution of the quaternized polymer and reacted at room temperature for 12-14 hours to obtain a reaction solution. S4. After dialysis purification of the reaction solution, freeze-dry to obtain the antibacterial polymer.

4. The anti-fouling medical coating material with antibacterial function according to claim 3, characterized in that, The mass ratio of ε-polylysine, N,N-dimethylformamide aqueous solution and glycidyl methacrylate solution in S1 is 8-10:100:1-1.

5.

5. The anti-fouling medical coating material with antibacterial function according to claim 3, characterized in that, The mass ratio of 1-bromododecane to the reaction solution containing the intermediate in S2 is 1:25-30.

6. The anti-fouling medical coating material with antibacterial function according to claim 3, characterized in that, In the S3 solution, the mass ratio of the quaternized polymer product to deionized water in the aqueous solution is 1:10-15; the mass ratio of hyaluronic acid oligomer, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N-hydroxysuccinimide, and deionized water in the hyaluronic acid oligomer activation solution is 1:0.5-0.8:0.5-0.8:10-15; and the mass ratio of the hyaluronic acid oligomer activation solution to the aqueous solution of the quaternized polymer is 1:1-2.

7. The anti-fouling medical coating material with antibacterial function according to claim 1, characterized in that, The crosslinking agent is N,N'-methylenebisacrylamide and / or ethylene glycol dimethacrylate.

8. The anti-fouling medical coating material with antibacterial function according to claim 1, characterized in that, The photoinitiator is an α-hydroxy ketone compound.

9. A method for preparing the anti-fouling medical coating material with antibacterial function according to any one of claims 1-8, characterized in that, Includes the following steps: Step 1: Weigh out the hydrophilic monomer, fluorinated low surface energy monomer, antibacterial polymer, crosslinking agent, photoinitiator and mixed solvent by weight and set aside. Step 2: Add the antibacterial polymer to the mixed solvent, seal and stir to obtain a homogeneous premixed solution; Step 3: While stirring, add the hydrophilic monomer, the fluorinated low surface energy monomer and the crosslinking agent, and stir for 30-50 minutes to obtain the prepolymer solution; Step 4: Under light-protected conditions, add photoinitiator to the prepolymer solution, stir for 15-30 min, and let stand at room temperature for 1-2 h to obtain the coating precursor solution. Step 5: After uniformly coating the coating precursor solution onto the surface of the medical substrate, cure it under ultraviolet light irradiation under inert gas protection, and then elute and purify it to obtain an anti-fouling medical coating with antibacterial function.

10. The method for preparing the antibacterial and antifouling medical coating material according to claim 9, characterized in that, The UV irradiation in step 5 means that the UV lamp with a main wavelength of 365 nm is irradiated at an intensity of 50-150 mW / cm 2 for 180-300 s.

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