Preparation method of antibacterial and anti-adhesion catheter coating containing perfluoropolyether

Abstract

The invention provides a preparation method of a perfluoropolyether-containing antibacterial and anti-adhesion catheter coating, and belongs to the technical field of material surface modification, and the preparation method specifically comprises the following three parts: 1, methyl ester terminated perfluoropolyether (PFPE-COOCH) and ethanediamine are subjected to an ester ammonolysis reaction to prepare aminated perfluoropolyether (PFPE-NH), and the structure of the aminated perfluoropolyether (PFPE-NH) is represented by FT-IR; 2, preparing copper particles by taking carboxylated chitosan as a dispersing agent, copper acetate as a copper source and sodium borohydride as a reducing agent, and verifying the matching effect of carboxylated chitosan and copper ions by FT-IR (Fourier Transform-Infrared Spectroscopy); 3, amino active sites are introduced into the MS polyether modified silica gel substrate, polymerization of dopamine (DA) is promoted to form a polydopamine (PDA) middle layer, copper particles and PFPE-NHH are loaded through chemical bonding, and the composite antibacterial coating is constructed. The performance of the coating is represented by static water contact angle test, SEM and the like, and the antibacterial and anti-adhesion effects under different bacterial concentrations and action time are systematically evaluated. The process is simple and controllable, the coating and the substrate are firmly combined, and the method is suitable for the fields of medical instruments and the like and has wide application prospects.

Description

Technical Field

[0001] This invention belongs to the field of medical polymer material surface modification technology, specifically relating to a modified silicone sheet with both antibacterial and hydrophobic properties prepared by multi-step functionalization modification based on copper and perfluoropolyether, and its preparation method, which is suitable for surface functionalization treatment of silicone rubber medical devices. Background Technology

[0002] Implantable medical devices play a vital role in improving healthcare and patients' quality of life. For example, urinary catheters (UCs) are often used as an alternative for bladder drainage and urine collection to prevent urinary retention. However, the catheter surface is prone to bacterial colonization and biofilm formation, leading to catheter-related urinary tract infections (CAUTIs) and other complications. In recent years, catheter coating technology has attracted significant attention, and developing a coating that combines antibacterial and hydrophobic properties has become a core research direction in the biomedical field.

[0003] Copper particles are widely used in the antibacterial field due to their excellent antibacterial activity and lack of drug resistance. For example, copper ions released by copper oxide can kill bacteria by reacting with thiol groups; copper nanoparticles can be internalized by bacteria and then directly interact with organelles, increasing reactive oxygen species levels, leading to DNA damage, mitochondrial dysfunction, and abnormal protein synthesis. In addition, copper oxide has photothermal properties under near-infrared light irradiation, and controllable antibacterial effects can be provided by adjusting the irradiation intensity and duration.

[0004] Perfluoropolyether (PFPE) is a class of fluoropolymers with -OCF2-, -OCF2CF2- and -OCF2CF(CF3)- as common chain units. It has good chemical stability, biocompatibility and hydrophobicity, and can be widely used in various coating materials. By introducing PFPE polymers, hydrophobic and antifouling effects can be achieved.

[0005] However, due to the inertness of the silicone substrate surface, directly loading copper particles and perfluoropolyether polymers onto the substrate surface is challenging, which severely restricts its clinical application in the medical field.

[0006] Against this backdrop, this invention employs modified silane polyether (MS polyether) and dopamine (DA) to modify the surface of an inert silica gel (SR) substrate. The invention uses MS polyether as the main coating material and 3-aminopropyltriethoxysilane (APTES) as the functionalizing molecule. The ethoxy group (-OC2H5) in the APTES molecule undergoes hydrolysis under specific reaction conditions to generate silanol groups (-Si-OH). These silanol groups can, on the one hand, achieve strong anchoring with the silica gel substrate surface through dehydration condensation to form Si-O-Si covalent bonds; on the other hand, they can undergo cross-linking reactions with the active groups contained in the MS polyether molecular chain to construct a three-dimensional network structure. Ultimately, a functionalized MS polyether coating (MS) rich in amino groups (-NH2) is successfully constructed on the silica gel surface. The amino-containing MS polyether coating can accelerate DA polymerization and uniformly deposit it on the silica gel surface, enriching its surface with more active groups, such as catechol, amino groups, and quinone structures. This, in turn, can stabilize the grafted copper antibacterial coating and the perfluoropolyether antifouling coating.

[0007] This invention addresses the susceptibility of traditional silicone catheters to bacterial infection by proposing an innovative surface modification scheme based on a functionalized modified substrate. This scheme prepares a coating with both antibacterial and hydrophobic properties, specifically comprising the following parts: First, copper particles coated with CS are prepared using copper acetate as the copper source, carboxylated chitosan (CS) as the dispersant, and sodium borohydride (NaBH4) as the reducing agent. The copper particles with amino groups on their surface are used to construct the antibacterial functional layer of the coating. Simultaneously, perfluoropolyether amide (PFPE-NH2) is prepared by the ammonolysis reaction of perfluoropolyether methyl ester (PFPE-COOCH3) and ethylenediamine, serving as the core component for the hydrophobic and anti-adhesion function of the coating. Second, using APTES as a crosslinking agent, MS polyether undergoes crosslinking polymerization on the surface of the silicone substrate through a moisture curing process, forming an MS polyether pre-coating. Building upon this, leveraging the self-polymerization properties of DA, a polydopamine (PDA) interfacial coating is generated on the surface of the MS polyether coating. The amino and carboxyl groups on the copper particle surface interact with the quinone structure and active groups such as catechol in the PDA molecule, achieving stable anchoring and high loading of the copper particles on the coating surface. Furthermore, given that the abundant catechol groups on the PDA surface can form covalent bonds with compounds containing thiol and amino groups through Michael addition or Schiff base reactions, the amino-functionalized PFPE-NH2 synthesized in this invention is grafted onto the PDA interfacial coating surface to complete the hydrophobic modification of the coating, ultimately constructing a bilayer functionalized coating with both antibacterial and anti-adhesion properties.

[0008] This invention achieves a dual breakthrough in functional component preparation and interface integration through multi-dimensional design and synergistic regulation. On the one hand, it successfully prepared copper particles with high antibacterial activity and synthesized PFPE-NH2 functional molecules with excellent hydrophobic properties, providing a material basis for the core antibacterial and anti-adhesion functions of the coating. On the other hand, it innovatively introduces a PDA interface coating as a "molecular bridge," which not only constructs abundant active sites in situ on the silicone substrate surface, significantly improving the grafting efficiency and interfacial binding stability of antibacterial components and hydrophobic functional molecules, but also successfully constructs a dense, synergistically effective integrated modification system of "substrate-intermediate layer-functional layer." This approach effectively overcomes the key technical bottlenecks commonly found in the functionalization of medical device surfaces, such as poor component compatibility and insufficient long-term functional effectiveness. It provides a novel technical path for the synergistic functionalization of antibacterial and antifouling properties of medical silicone materials, possessing both scientific innovation and clinical translational value. This has significant practical application and promotional value for reducing the incidence of medical device-associated infections (HAI) and improving medical safety. Summary of the Invention

[0009] The core content of this invention mainly revolves around three key technologies: First, it prepares two types of core functional components—copper-based functional particles with highly efficient antibacterial activity and PFPE-NH2 functional molecules with excellent hydrophobic and anti-adhesion properties, laying the material foundation for the dual functionality of the coating; Second, it innovatively introduces an MS polyether pre-coating modification strategy, utilizing the good compatibility and surface activity of MS polyether with the substrate to provide support for the uniform deposition and firm bonding of the subsequent dopamine (PDA) interfacial coating, achieving efficient modification of the inert silicone substrate and solving the problem of the difficulty in functionalizing the surface of traditional inert silicone substrates; Third, based on the modified substrate, it orderly loads the above-mentioned antibacterial copper particles and hydrophobic perfluoropolyether amide functional molecules through interfacial interaction regulation, ultimately constructing a functional coating with both antibacterial and excellent hydrophobic and anti-adhesion properties.

[0010] The purpose of this invention is to provide a modified silicone sheet with both high-efficiency antibacterial and hydrophobic properties, and its preparation method. This method, through a multi-step synergistic functionalization modification route, achieves the introduction of active groups on the substrate surface, stable loading of antibacterial functional components, and precise construction of a hydrophobic functional layer. It effectively solves the core defects of traditional silicone materials, such as insufficient antibacterial properties and susceptibility to bacterial adhesion, significantly improving the overall performance of the silicone sheet and providing technical support for its application in medical devices, biomaterials, and other fields.

[0011] To achieve the above objectives, the present invention provides a method for preparing a perfluoropolyether-containing antibacterial and anti-adhesion catheter coating, specifically comprising the following steps: The first step is to introduce a silane-modified polyether (MS polyether) pre-coating onto the surface of the silicone sheet, giving it an amino content. The second step involves further introducing a polydopamine (PDA) interfacial coating onto the MS polyether pre-coated surface obtained in the first step, providing sufficient active sites for the subsequent loading of antibacterial and hydrophobic coatings. The third step involves preparing copper particles using carboxylated chitosan (CS) as a dispersant, copper acetate as a copper source, and sodium borohydride (NaBH4) as a reducing agent, which serve as the core component of the antibacterial coating. The fourth step involves preparing perfluoropolyether amide (PFPE-NH2) as the core component of the hydrophobic coating through the ammonolysis reaction of perfluoropolyether methyl ester (PFPE-COOCH3) and ethylenediamine. Step 5: Load the copper particles prepared in step 3 onto the MS polyether pre-coating prepared in step 2 to obtain the antibacterial coating MS-PDA-Cu; then load the perfluoropolyether amide prepared in step 4 onto the MS-PDA-Cu coating to obtain the composite coating MS-PDA-Cu-F, which has both hydrophobic and antibacterial properties.

[0012] Furthermore, the preparation process of the MS polyether pre-coating in the first step is as follows: weigh a certain mass of MS polyether and 3-aminopropyltriethoxysilane (APTES) to a mass ratio of 9:1, fully dissolve them in chloroform (CHCl3), add a certain amount of catalyst dibutyltin dilaurate; use the dip-coating method to dip a silicone sheet into the solution and then place it in air to cure for 24 hours to obtain the MS polyether pre-coating.

[0013] Furthermore, the preparation process of the polydopamine interface coating in the second step is as follows: a DA solution with a concentration of 4 mg / ml is prepared using a Tris solution with a pH of 8.5; the MS polyether pre-coating prepared according to claim 2 is immersed in the DA solution for 24 h, and after the reaction is completed, an interface coating MS-PDA with active groups is obtained.

[0014] Furthermore, the preparation process of the copper particles in the third step is as follows: a certain mass of CS is weighed and dissolved in deionized water; then a copper acetate solution with a concentration of 40 mmol / L is added, and the mixture is stirred continuously until a uniform blue system is formed; then a NaBH4 solution with a concentration of 56 mmol / L is added as a reducing agent, and the molar ratio of copper acetate to NaBH4 is controlled at 1:2. After the addition is complete, the reaction continues for 3 hours; after the reaction is completed, the product is placed in a high-speed centrifuge and centrifuged for 10 minutes, and the bottom precipitate is collected; after redispersing the precipitate with deionized water, the centrifugation-washing operation is repeated 3 times to remove unreacted raw materials and by-products; finally, the washed precipitate is placed in a vacuum drying oven and dried at 60°C to obtain copper particles.

[0015] Furthermore, the preparation process of PFPE-NH2 in step four is as follows: PFPE-COOCH3 and excess ethylenediamine are placed in a round-bottom flask, hydrofluoroether (HFE) is added as a reaction solvent, and then triethylamine is added as a catalyst; the reaction apparatus is placed in a nitrogen protective atmosphere, heated to 80°C, and the reaction is magnetically stirred at this temperature for 6 hours; after the reaction is completed, saturated sodium chloride aqueous solution is added to the round-bottom flask to remove the residual ethylenediamine and triethylamine after the reaction, and finally the residual HFE solvent is removed by rotary evaporator, and the target product PFPE-NH2 with amino functional groups is finally prepared.

[0016] Furthermore, the copper particles prepared in the third step were prepared into a copper particle dispersion with a concentration of 1 mg / ml; the interface coating MS-PDA prepared in the second step was immersed in the dispersion for 24 h to obtain the antibacterial coating MS-PDA-Cu; the PFPE-NH2 prepared in the fourth step was prepared into a 1.5% wt solution; the MS-PDA-Cu coating was immersed in the solution for 24 h to obtain the composite coating MS-PDA-Cu-F with both antibacterial and hydrophobic properties.

[0017] Another aspect of the present invention provides an application of a method for preparing a perfluoropolyether-containing antibacterial and anti-adhesion conduit coating.

[0018] Compared with existing technologies, the preparation method of the perfluoropolyether-containing antibacterial and anti-adhesion catheter coating of the present invention has the following advantages: 1. Enhanced Interfacial Bonding Mechanism: This technology introduces amino groups onto the silicone sheet surface through the silanol condensation reaction between APTES and MS polyether, providing abundant active binding sites for subsequent PDA coating deposition. Utilizing the self-polymerization properties of DA under weakly alkaline conditions, a dense and highly adhesive "universal adhesion layer" can be formed on the surface of the MS polyether modified layer. The surface is rich in amino and catechol active groups, which can form strong interactions (hydrogen bonds, covalent bonds, and electrostatic interactions) with the subsequently loaded copper particles and PFPE-NH2. This fundamentally solves the technical pain points of weak adhesion between traditional coatings and silicone substrates and easy detachment after long-term use, significantly improving the service stability of the coating.

[0019] 2. Optimized Antibacterial Component Design: CS is used as a dispersant, stabilizer, and coating agent for copper particles. The carboxyl and amino groups on its molecular chain can form stable complexes with copper ions through coordination, achieving tight encapsulation during copper particle formation. This effectively inhibits particle aggregation, ensuring uniform dispersion of the antibacterial components in the coating and improving the uniformity of the antibacterial effect. After reduction to copper particles using NaBH4, the biocompatibility of CS significantly reduces the cytotoxicity of the copper particles, allowing the coating to maintain high antibacterial activity while ensuring biocompatibility, making it particularly suitable for applications involving contact with biological tissues, such as medical silicone catheters.

[0020] 3. Achievement of hydrophobic and antifouling functions: Through the amidation reaction of PFPE-COOCH3 with ethylenediamine, amino groups are precisely introduced at the end of the PFPE molecular chain, endowing it with the ability to covalently bond with the active groups (carboxyl groups, catechol, quinone structures, etc.) on the surface of the PDA coating and copper particles, achieving directional grafting and uniform distribution of hydrophobic segments on the coating surface. The unique low surface energy of PFPE can significantly reduce the hydrophilicity of the coating surface, giving the coating excellent hydrophobic and antifouling properties, effectively solving the problem of single antibacterial coatings being easily contaminated by body fluids, secretions, etc., and extending the service life of the coating.

[0021] 4. Summary of Comprehensive Performance Advantages: This invention organically combines antibacterial components (copper particles) and hydrophobic and antifouling components (PFPE segments) through a multi-step modification process to construct a composite coating on the surface of a silicone catheter that possesses highly efficient antibacterial properties, excellent hydrophobicity and antifouling capabilities, and strong interfacial adhesion. This coating solves multiple technical problems of traditional medical silicone catheters, such as easy bacterial growth, easy contamination, and easy coating peeling, providing a practical and feasible technical solution for optimizing the performance of medical catheters and possessing significant practical application value. Attached Figure Description

[0022] Figure 1 This is a synthetic route diagram for perfluoropolyether amides; Figure 2 Infrared characterization of the copper ion-carboxylated chitosan complex. Figure 3 Infrared characterization of the prepared perfluoropolyether amide; Figure 4 A diagram showing the water contact angle of the prepared conduit coating; Figure 5 A scanning electron microscope image of the prepared catheter coating; Figure 6(a) shows the relationship between the antibacterial rate of the coating and the concentration of the bacterial solution; (b) shows the bacterial coating pattern. Figure 7(a) shows the relationship between the antibacterial rate of the coating and the antibacterial time; (b) shows the bacterial coating pattern. Figure 8 Image showing the antibacterial adhesion of the prepared catheter coating; Detailed Implementation

[0023] Example 1 Preparation of core functional components 1. Preparation of copper particles: Dissolve 0.2 g CS in 2 ml of deionized water and stir until completely dissolved. Take 0.5 ml of the above solution and add 1 ml of 40 mM copper acetate solution, and continue stirring for 30 min to allow copper ions to fully coordinate with the carboxyl and amino groups of CS. Then, add 1.5 ml of 56 mM NaBH4 solution dropwise, and continue stirring for 40 min after the addition is complete to obtain a copper particle dispersion. Wash three times with deionized water, centrifuging at 8000 rpm for 10 min each time, and collect the precipitate. Finally, dry the precipitate under vacuum at 60℃ for 2 h to obtain copper particles.

[0024] 2. Synthesis of PFPE-NH2: 2.00 g of PFPE-COOCH3 and 0.4 g of ethylenediamine were dissolved in 5 ml of HFE. 400 μL of triethylamine was added as a catalyst, nitrogen gas was introduced, and the mixture was refluxed at 80 °C for 6 h. After the reaction was complete, an equal volume of saturated sodium chloride solution was added to wash three times to remove unreacted triethylamine and ethylenediamine. The lower organic phase was collected, and the HFE solvent was removed by rotary evaporation at 50 °C to obtain pure, pale yellow, viscous PFPE-NH2. The specific synthetic route is shown in the appendix. Figure 1 .

[0025] 3. Characterization of core components: The complexes of copper ions and CS were characterized by Fourier transform infrared spectroscopy (FTIR). FTIR analysis showed (see attached image). Figure 2 ), 1731cm -1 The disappearance of the carboxyl peak and 1633 cm -1 The enhancement of the peak demonstrates the successful coordination of copper ions with CS.

[0026] PFPE-NH2 was characterized by FTIR, and the FTIR analysis showed (see attached image). Figure 3 ), 1795cm -1 The peak at the ester group disappears at 1705 cm⁻¹. -1 A characteristic peak for amide bonds appeared at 1190 cm⁻¹. -1 The peak at 3370 cm⁻¹ represents the absorption peak of the CF bond. -1 An absorption peak for NH appears at 1540 cm⁻¹. -1 The presence of a CN absorption peak at the specified location, along with the above characteristic peaks, collectively confirms the successful synthesis of PFPE-NH2.

[0027] Example 2 Preparation of antibacterial medical catheter coating: 1. Preparation of MS polyether coating: Accurately weigh 0.9 g of MS polyether and 0.1 g of APTES, add 2 ml of CHCl3 solution, and sonicate to fully dissolve the MS polyether. Then add 0.01 g of dibutyltin dilaurate (1% of the total mass of MS polyether and APTES) as a catalyst to the mixed solution. Immerse the pretreated silicone sheet into the MS polyether solution using the dip-coating method, and then cure in moisture for 24 h to obtain the MS polyether coating.

[0028] 2. Preparation of MS-PDA coating: Weigh an appropriate amount of Tris and dissolve it in deionized water to prepare 20 mL of Tris-HCl buffer solution with pH=8.5. Add 0.08 g of dopamine hydrochloride to this buffer solution and stir magnetically for 15 min until completely dissolved to obtain a DA reaction solution with a concentration of 4 mg / mL. Immerse the MS coating in the DA solution and observe the silica gel sheet surface every 24 h to see if a dense PDA coating has formed. After observing the appearance of a black coating, remove the sheet and rinse it with plenty of deionized water 2-5 times to remove free DA from the surface. Then place it in a vacuum drying oven at 50℃ for 12 h to obtain the MS-PDA coating.

[0029] 3. Preparation of MS-PDA-Cu coating: The copper particles prepared in Example 1 were dispersed in deionized water to prepare a 1 mg / ml dispersion. The MS-PDA-coated silica sheet was immersed in this dispersion and statically soaked for 6 hours to allow the copper particles to fully combine with the amino and catechol groups on the PDA surface. After removal, it was first dried at 60°C for 1 hour, then rinsed with deionized water to remove free copper particles, and dried again to obtain the MS-PDA-Cu-coated silica sheet.

[0030] 4. Preparation of MS-PDA-Cu-F coating: Accurately weigh 0.075 g of PFPE-NH2 obtained in Example 1 and dissolve it in 5.0 ml of HFE to obtain a 1.5% wt solution. Seal and immerse the MS-PDA-Cu coated silicone sheet in the prepared solution and react at room temperature for 12 h. After the reaction, clean the surface of residual PFPE-NH2 with a large amount of HFE. Finally, dry in a vacuum dryer at 80 °C for 12 h to obtain an MS-PDA-Cu-F coated silicone sheet with both antibacterial and hydrophobic properties.

[0031] Characterization of antibacterial medical catheter coatings: The water contact angles of the SR, MS, MS-PDA, MS-PDA-Cu, and MS-PDA-Cu-F coatings were tested using a contact angle meter, and the results are shown in the attached figure. Figure 4As shown, using pure silicone sheet SR as a control group, its inherent hydrophobicity resulted in a contact angle of approximately 110°. After modification with MS polyether, the contact angle of the coating slightly increased to around 113°. When a PDA coating was deposited on the surface, the large number of phenolic hydroxyl and amino groups in the PDA molecular structure imparted hydrophilicity to the surface, causing the contact angle to drop significantly to approximately 60°. However, after loading copper particles onto the surface, the change in surface roughness caused by the copper particles increased the contact angle to 85°, while the coating still maintained strong hydrophilicity. After further modification with PFPE-NH2, the contact angle of the MS-PDA-Cu-F coating reached approximately 120°. These regular changes in contact angle further confirm the successful loading of each functional layer onto the substrate surface.

[0032] The surface morphology of the coating was analyzed using scanning electron microscopy (SEM) (see attached image). Figure 5 Figures (a, b, c, d, and e) show the coatings: SR, MS, MS-PDA, MS-PDA-Cu, and MS-PDA-Cu-F, respectively. As shown in the figures, the coating in Figure a has a relatively rough surface, while the coating in Figure b, loaded with MS polyether, is smoother. Figure c has a rougher surface compared to Figure b, and a dense coating is clearly visible, indicating successful PDA deposition on the SR-MS surface. Figure d shows a large number of particles on the surface, indicating successful loading of copper particles onto the PDA surface. Figure e shows a thin coating covering the surface, and the presence of PDA coating and copper particles at the bottom layer indicates successful bonding of PFPE-NH2.

[0033] Example 3 Antibacterial test: The first part investigated the effect of bacterial concentration on the antibacterial activity of the MS-PDA-CU-F coating. A fixed incubation time of 45 min was set, with bacterial concentrations of 10... 8 CFU / mL, 10 7 CFU / mL, 10 6 CFU / mL, 10 5 CFU / mL of Escherichia coli ( E. coli ) and Staphylococcus aureus ( S.aureusThe test strain was used to evaluate the antibacterial effect by colony counting. The original silica gel sheet was set as a blank control group. The specific operation was as follows: (1) Sample pretreatment: The MS-PDA-Cu-F coated silica gel sheet (finished product) was rinsed with PBS buffer, dried and then placed in a clean bench for UV sterilization for 2 hours. (2) Bacterial culture: The pretreated sample was placed in a sterile culture dish. 20 μL of bacterial solution of different concentrations was dropped onto the coating surface and covered with a 0.5 cm × 0.5 cm sterile PE sheet to ensure that the bacterial solution and coating were in full contact. A bottle cap containing sterile physiological saline was placed in the culture dish to maintain humidity and it was placed in a constant temperature incubator at 37℃ for 45 min. (3) Colony counting: After the culture was completed, the sample was taken out and placed in a sterile beaker containing 2 mL of PBS solution. The sample was sonicated for 2 min to disperse the attached bacteria. 50 μL of a suitable concentration of dispersion was evenly spread on a solid culture medium and cultured at 37℃ for 18 h. The colony count was then performed and the inhibition rate was calculated. The blank control group used a silicone sheet instead of the coated catheter material, and the remaining operating steps were completely consistent with the above process.

[0034] The second part investigates the effect of antibacterial time on the antibacterial rate of the coating. Using a concentration of 10... 6 CFU / mL E. coli and S.aureus Using MS-PDA-CU-F as the research subject, the antibacterial activity was investigated by setting different incubation times. The specific operation was the same as described above.

[0035] Antibacterial test characterization: As shown in Figure 6(a), the colony counting method was used to systematically calculate the effect of MS-PDA-CU-F coating on different initial concentrations (10) under an action time of 45 min. 5 CFU / mL, 10 6 CFU / mL, 10 7 CFU / mL, 10 8 CFU / mL E. coli and S.aureus The antibacterial rate. Figure 6(b) shows a visual photograph of the plate colonies at the corresponding concentrations, intuitively presenting the differences in the antibacterial effect of the coating. The experimental results show that when the initial concentration of the two pathogenic bacteria is 10... 5 ~10 7 At CFU / mL, the coating maintained an antibacterial rate of over 99%, demonstrating highly efficient antibacterial activity. However, when the bacterial concentration increased to 10... 8 At CFU / mL, the antibacterial rate of the coating decreased significantly, and its antibacterial effect was significantly reduced. E. coli The antibacterial rate decreased to 10%, which is effective against... S.aureus The antibacterial rate decreased to approximately 50%. These results indicate that the antibacterial rate of this antibacterial coating decreases with increasing initial concentration of pathogenic bacteria, but remains relatively high for 10... 5~10 7 Bacteria within the CFU / mL concentration range still exhibit excellent antibacterial properties, meeting the antibacterial application requirements in relevant scenarios.

[0036] As shown in Figure 7(a), the colony counting method was used to systematically investigate the effect of MS-PDA-Cu-F coating at different reaction times (15 min, 30 min, 45 min, 60 min) on an initial concentration of 10. 6 CFU / mL E. coli and S.aureus The antibacterial properties of the coating are shown in Figure 7(b), which is a visual photograph of the bacterial colonies on the plate at the corresponding treatment time, intuitively reflecting the change in the antibacterial effect of the coating over time. Experimental results indicate that the coating is effective against *Escherichia coli*. E. coli The antibacterial rate was less than 50% after 15 minutes of application, and less than 80% after 30 minutes. However, when the application time was extended to 45 minutes and 60 minutes, the antibacterial rate reached over 99%. (This is in contrast to the previous description of the coating.) S.aureus The coating exhibited a faster antibacterial response; after 15 minutes of action, the inhibition rate was less than 80%, but it significantly increased to over 95% after 30 minutes, and further reached over 99% after 45 and 60 minutes. These results clearly demonstrate that the antibacterial rate of the MS-PDA-Cu-F coating increases significantly with prolonged action time, and its antibacterial action against Staphylococcus aureus is faster than that against Escherichia coli. It effectively kills both pathogenic bacteria after 45 minutes, exhibiting excellent time-dependent antibacterial properties.

[0037] Example 4 Antibacterial adhesion test To systematically evaluate the antibacterial adhesion performance of the MS-PDA-Cu-F composite coating, blank silicone sheets were used as the control group, and MS-PDA-Cu-F coated silicone sheets were used as the experimental group in parallel experiments. The specific procedures were as follows: Both samples were placed in sterile test tubes, and 1 mL of a 10% concentration of [unspecified substance] was added to each test tube. 6 CFU / mL E. coli or S.aureusThe bacterial suspension was prepared, ensuring the sample was completely submerged. The test tubes were then placed in a constant-temperature shaker and dynamically cultured at 37°C and 200 rpm for 24 hours. After culture, the samples were removed and gently rinsed three times with PBS to remove any loosely adhered airborne bacteria. The samples were then transferred to a small beaker containing 2 mL of PBS and sonicated for 3 minutes to allow the bacteria firmly adhering to the material surface to detach and disperse evenly in the buffer solution. 50 μL of the sonicated bacterial suspension was evenly spread onto the surface of LB solid medium and incubated upside down at 37°C for 18 hours. The number of colonies on each culture medium was counted using a colony counting method to calculate the amount of bacteria adhering to the material surface per unit area, thus quantitatively evaluating the antibacterial adhesion efficacy of the MS-PDA-Cu-F coating.

[0038] Antibacterial adhesion test characterization Appendix Figure 8 For blank silicone sheets and MS-PDA-Cu-F coated modified silicone sheets in E. coli and S.aureus Visual characterization of bacterial colonies after dynamic incubation at 37℃ and 200rpm for 24 hours. As shown in the figure, no clearly visible colonies were observed on the LB solid medium surface of the MS-PDA-Cu-F coated silica sheet in the experimental group, indicating that after PBS washing and ultrasonic desorption treatment, almost no firmly adhered bacteria remained on the coating surface, demonstrating a significant anti-bacterial adhesion effect. In the control group, after treatment with the same experimental procedure, a large number of densely distributed colonies appeared on the surface of the medium. The colonies were well-formed and showed good growth, further confirming that the unmodified silica substrate surface, due to its inherent physicochemical properties, effectively inhibited bacterial adhesion. E. coli and S.aureus All exhibited a strong tendency for bacterial adhesion. However, the MS-PDA-Cu-F composite coating demonstrated excellent anti-adhesion properties against bacteria with different cell wall structures, effectively hindering the initial adhesion and colonization process of bacteria on the material surface.

Claims

1. A method for preparing a perfluoropolyether-containing antibacterial and antiadhesive catheter coating, characterized in that, The method comprises the following steps: The first step is to introduce a silane-modified polyether (MS polyether) pre-coating layer on the surface of a silica gel sheet to make the surface have amino groups. The second step is to further introduce a polydopamine (PDA) interface coating layer on the surface of the MS polyether pre-coating layer obtained in the first step, so as to provide sufficient active sites for the subsequent loading of an antibacterial coating and a hydrophobic coating. The third step is to prepare copper particles by taking carboxymethyl chitosan (CS) as a dispersant, copper acetate as a copper source and sodium borohydride (NaBH4) as a reducing agent, so as to serve as a core component of the antibacterial coating. The fourth step is to prepare a perfluoropolyether amide (PFPE-NH2) by means of an ester aminolysis reaction of perfluoropolyether methyl ester (PFPE-COOCH3) and ethylenediamine, so as to serve as a core component of the hydrophobic coating. The fifth step is to load the copper particles prepared in the third step on the MS polyether pre-coating layer prepared in the second step to obtain an antibacterial coating MS-PDA-Cu, and then load the perfluoropolyether amide prepared in the fourth step on the MS-PDA-Cu coating to obtain a composite coating MS-PDA-Cu-F which has both hydrophobic and antibacterial properties.

2. A method of making a perfluoropolyether-containing antibacterial and antiadhesive catheter coating according to claim 1, characterized in that: The preparation process of the MS polyether pre-coating layer in the first step is as follows: a certain amount of MS polyether and 3-aminopropyltriethoxysilane (APTES) are weighed and dissolved in chloroform (CHCl3) in a mass ratio of 9:1, and a certain amount of a catalyst dibutyltin dilaurate is added; the silica gel sheet is dipped in the solution by using a pulling method and then placed in air for solidification for 24 hours to obtain the MS polyether pre-coating layer.

3. A method of making a perfluoropolyether-containing antibacterial and antiadhesive catheter coating according to claim 1, characterized in that: The preparation process of the polydopamine interface coating layer in the second step is as follows: a DA solution with a concentration of 4 mg / ml is prepared by using a Tris solution with a pH of 8.5; the MS polyether pre-coating layer prepared in the first step is immersed in the DA solution for 24 hours, and an interface coating layer MS-PDA with active groups is obtained after the reaction.

4. A method of making a perfluoropolyether-containing antibacterial and antiadhesive catheter coating according to claim 1, characterized in that: The preparation process of the copper particles in the third step is as follows: a certain amount of CS is weighed and dissolved in deionized water; then a copper acetate solution with a concentration of 40 mmol / L is added, and continuous stirring is performed until a uniform blue system is formed; a NaBH4 solution with a concentration of 56 mmol / L is added as a reducing agent, the molar ratio of copper acetate to NaBH4 is controlled to be 1:2, and after the dropwise addition is completed, the reaction is continued for 3 hours; after the reaction is completed, the product is placed in a high-speed centrifuge and centrifuged for 10 minutes to collect the bottom precipitate; After the precipitate is redispersed with deionized water, the centrifugation-washing operation is repeated for 3 times to remove unreacted raw materials and byproducts, and finally the washed precipitate is placed in a vacuum drying oven and dried at 60°C to obtain the copper particles.

5. A method of making a perfluoropolyether-containing antibacterial and antiadhesive catheter coating according to claim 1, characterized by: The preparation process of PFPE-NH2 in the fourth step is as follows: placing PFPE-COOCH3 and excess ethylenediamine in a round-bottom flask, adding hydrofluoroether (HFE) as a reaction solvent, and then adding triethylamine as a catalyst; placing the reaction device in a nitrogen protective atmosphere, heating to 80°C, and stirring the reaction at this temperature for 6 h; after the reaction is completed, adding saturated sodium chloride aqueous solution to the round-bottom flask to remove the residual ethylenediamine and triethylamine after the reaction, and finally removing the residual HFE solvent by a rotary evaporator to finally prepare the target product PFPE-NH2 with an amino functional group.

6. A method of making a perfluoropolyether-containing antibacterial and antiadhesive catheter coating according to claim 1, characterized by: The preparation process of the antibacterial coating and the hydrophobic coating in the fifth step is as follows: The copper particles prepared by the method of claim 4 are configured into a copper particle dispersion liquid with a concentration of 1 mg / ml; the interface coating MS-PDA coating prepared by the method of claim 3 is immersed in the dispersion liquid for 24 h to obtain an antibacterial coating MS-PDA-Cu; PFPE-NH2 prepared by the method of claim 5 is configured into a solution with a concentration of 1.5%wt; the MS-PDA-Cu coating is immersed in the solution for 24 h to obtain a composite coating MS-PDA-Cu-F with both antibacterial and hydrophobic properties.

7. Use of the coating prepared by the method of claim 1 or 6 in an antibacterial medical device.

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