Preparation of silver ion modified antibacterial medical catheter coating

Abstract

The invention provides a preparation method of a silver ion modified antibacterial medical catheter coating, which comprises the following specific steps: preparing a mixed pre-gel transparent solution from 2-acrylamido-2-methylpropanesulfonic acid (AMPS) and butyl acrylate (BA) according to a mass ratio of 3: 7, adding an MBA cross-linking agent and a TPO photoinitiator, and carrying out ultraviolet curing to form a Poly (AMPS-co-BA) coating with an interpenetrating network structure; after complete sodium ionization of sulfonic groups is achieved through pretreatment of a 10 wt% NaOH solution, an AgNO3 solution is adopted for ion replacement, and the loading amount of silver ions is stabilized in a high range in combination with an ultrasonic-constant current cleaning technology; finally, the Poly (AMPS-co-BA)-Ag coating is formed on the surface layer of the silica gel catheter through the same preparation method, and SR-Ag is obtained, the steps are skilled and ordered, the film has good toughness and good hydrophilicity, and experimental results show that the coating has long-acting antibacterial ability.

Description

Technical Field

[0001] The present invention belongs to the technical field of medical functional polymer materials, and particularly relates to a silver ion modified antibacterial coating of a copolymer hydrogel based on the copolymerization of 2-acrylamido-2-methyl-1-propane sulfonic acid (AMPS) and butyl acrylate (BA), and a preparation method thereof, which is applicable to the surface functionalization treatment of silicone rubber medical devices. Background Art

[0002] With the rapid development of modern medical technology, the usage of interventional medical devices (such as antibacterial dressings, etc.) in clinical treatment has been increasing year by year. However, these medical devices are prone to bacterial contamination during use, leading to the occurrence of infections, seriously threatening the health and life safety of patients. Therefore, the development of medical materials with high antibacterial performance has become one of the important research directions in the current biomedical field. Silver ions (Ag + ) as a broad-spectrum antibacterial agent, its antibacterial effect stems from multiple synergistic mechanisms: disrupting the structural integrity of microbial cell membranes through electrostatic interactions; binding to the active center of bacterial metabolic enzymes to interfere with the energy metabolism pathway; inducing genetic material damage to inhibit pathogen proliferation. However, the silver-containing antibacterial materials prepared by traditional physical blending and chemical deposition methods face key technical challenges: the insufficient dispersion uniformity of the active components in the matrix is prone to cause local concentration gradients, resulting in significant spatial heterogeneity of antibacterial efficacy; the uncontrolled release characteristics of silver ions cause a large amount of loss in the initial stage, making it difficult to maintain the long-term antibacterial threshold concentration. These inherent defects not only weaken the antibacterial persistence of the material, but may also cause biocompatibility problems due to excessive release of silver ions, severely restricting its clinical application in the field of medical device surface modification.

[0003] In this context, ion exchange technology, as an efficient and controllable surface modification method, has attracted much attention due to its precise ion loading characteristics and shows great potential in the research and development of medical antibacterial materials. This technology can achieve the stable loading of antibacterial components through the directional replacement of metal ions by surface functional groups of materials. Among them, sulfonic acid group-containing polymers show unique advantages in silver ion loading due to their abundant negatively charged sites. However, the conventional impregnation method is easily interfered by competing ions, resulting in low silver ion loading efficiency and uneven distribution, seriously affecting the durability of antibacterial performance.

[0004] In response to the limitations of traditional silver ion loading techniques, this study proposes an innovative solution based on a functionalized polymer matrix: First, a gradient copolymerization network of AMPS (2-acrylamido-2-methylpropanesulfonic acid) and butyl acrylate is constructed through molecular structure design, and ordered ion transport channels are formed using the spatial arrangement characteristics of the sulfonic acid groups in AMPS molecules; Second, a stepwise ion exchange process is innovatively adopted. First, the sulfonic acid groups in the polymer are converted into the -SO3Na form through sodium ionization pretreatment, significantly improving the subsequent silver ion exchange efficiency; On this basis, through the directional displacement reaction of a gradient concentration AgNO3 solution, the spatial controllable loading of silver ions in the polymer matrix is achieved; Finally, combined with ultrasonic-constant flow cleaning technology, surface free silver ions are effectively removed to ensure the interfacial stability of the loaded silver ions.

[0005] Through a three-dimensional collaborative strategy of "structural design - process optimization - surface regulation", this technical system successfully solves the key technical bottlenecks such as uneven silver ion distribution, low loading efficiency, and uncontrollable release in traditional methods, providing a new solution with clinical application value for the surface antibacterial functionalization of medical devices. Summary of the Invention

[0006] The content of this invention mainly includes two parts. One is to construct a silver ion-modified Poly(AMPS-co-BA)-Ag antibacterial gel coating based on ion exchange; the other is to form a long-acting antibacterial coating SR-Ag by co-melting the modified gel coating and a silicone catheter through ultraviolet curing technology.

[0007] The purpose of this invention is to provide a method for surface modification of silicone rubber with both long-acting antibacterial and interfacial stability.

[0008] I. Technical Solution of the Invention:

[0009] The preparation method of Poly(AMPS-co-BA)-Ag is as follows:

[0010] 1. Preparation of pre-gel transparent solution:

[0011] Using N,N-dimethylformamide (DMF) as a solvent, add the copolymerization monomers of 2-acrylamido-2-methylpropanesulfonic acid (AMPS) and butyl acrylate (BA) in proportion, and control the mass ratio of the two to be 3:7. Add N,N'-methylenebisacrylamide (MBA) as a cross-linking agent and 2,4,6-trimethylbenzoyl-diphenylphosphine oxide (TPO) as a photoinitiator. Stir and mix at room temperature to form a pre-gel transparent solution.

[0012] 2. Preparation of Poly(AMPS-co-BA) coating:

[0013] The silicone rubber substrate was ultrasonically cleaned and surface-activated pretreated. The substrate was vertically immersed in a transparent solution and slowly withdrawn after sufficient infiltration. A UV light source was used to vertically irradiate the surface of the substrate to initiate a photopolymerization reaction to form a copolymer cross-linked coating (Poly(AMPS-co-BA) copolymer coating), which is abbreviated as Poly(AMPS-co-BA). The cured sample was transferred to a vacuum drying oven and treated at a constant temperature to remove residual solvents and strengthen the interfacial bonding.

[0014] 3. Sodium ionation of the coating:

[0015] The Poly(AMPS-co-BA) coating was immersed in a sodium hydroxide solution for sulfonic acid group sodium ionation treatment. Three washes were carried out in sequence: ultrasonic cleaning, deionized water rinsing, and centrifugal dehydration. Then the prepared coating was vacuum dried to obtain a sodium ionized modified coating.

[0016] 4. Silver + ionation of the coating:

[0017] The Poly(AMPS-co-BA)-Na coating was immersed in a silver nitrate solution, and silver ions were loaded through a displacement reaction between the sulfonic acid group sodium salt and silver ions to obtain a Poly(AMPS-co-BA)-Ag modified coating loaded with silver ions. Three-level washing was carried out in sequence: ultrasonic cleaning to remove free ions, deionized water rinsing, and nitrogen purging. Then, under light-shielded conditions, the Poly(AMPS-co-BA)-Na coating was vacuum dried to obtain a silver ion-modified Poly(AMPS-co-BA)-Ag coating.

[0018] The medical catheter coating of the present invention is obtained by coating Poly(AMPS-co-BA)-Ag on the surface of a silicone catheter, which is formed by means of the hydrophobic effect of the BA monomer and the silicone surface. The preparation method of the antibacterial medical catheter coating is as follows:

[0019] The medical silicone catheter was immersed in a pre-prepared AMPS / BA mixed pre-gel transparent solution, and UV light curing was carried out to form a cross-linked coating. Vacuum drying was carried out to remove solvents and densify the coating. Then the coating was immersed in a sodium hydroxide solution for sulfonic acid group sodium ionation, and ultrasonic assistance was used to strengthen the reaction. It was then transferred to a silver nitrate solution for silver ion displacement to achieve directional loading of silver ions. Finally, three-level washing of ultrasonic cleaning, deionized water rinsing, and nitrogen purging was carried out in sequence. Finally, the modified coating was subjected to light-shielded constant current drying operation to obtain an antibacterial coating SR-Ag.

[0020] Technical analysis of the present invention:

[0021] Silver ions, as the core of the antibacterial function, are stably loaded onto the polymer network through ion exchange technology. Their sustained release characteristics effectively inhibit the proliferation of microorganisms. Based on the copolymerization system of AMPS and butyl acrylate, a three-dimensional interpenetrating network structure is formed by ultraviolet photopolymerization, providing a directional channel for ion transport. The stepwise ion replacement process first activates the sulfonic acid groups through sodium ion pretreatment, and then realizes the spatially controllable loading of silver ions with a certain concentration of silver solution. Combining with surface cleaning technology to eliminate free ions, ensuring the uniform distribution and long-term sustained release of antibacterial components. After surface modification of the medical silicone catheter, a composite interface of chemical bonding and physical anchoring is formed with the antibacterial coating, synergistically with the chemical bactericidal characteristics of silver ions, significantly reducing bacterial adhesion and blocking biofilm formation, thus comprehensively improving the antibacterial performance and clinical safety of medical devices.

[0022] In summary, the present invention provides a preparation of a silver-containing modified Poly(AMPS-co-BA) antibacterial gel coating. And it is coated on the surface of the silicone catheter to design an effective long-acting antibacterial silicone catheter coating. Brief Description of the Drawings

[0023] Figure 1 SEM test diagram for preparing the modified coating.

[0024] Figure 2 Infrared characterization diagram for preparing the AMPS polymer.

[0025] Figure 3 XPS test diagram for preparing the modified coating.

[0026] Figure 4 Water contact angle diagram for the prepared medical catheter coating.

[0027] Figure 5 Bacterial coating diagram for the prepared medical catheter coating. Detailed Description of the Invention

[0028] Example 1

[0029] Preparation of the Modified Coating

[0030] The preparation method of the modified coating includes three steps:

[0031] 1. Using N,N-dimethylformamide (DMF) as a solvent, add 8 wt% to 20 wt% of 2-acrylamido-2-methylpropanesulfonic acid (AMPS) and 20 wt% to 32 wt% of butyl acrylate (BA) as comonomers by mass percentage; add 0.6 mol% of N,N'-methylenebisacrylamide (MBA) as a crosslinking agent based on the molar amount of AMPS, and supplement with 20 mg of 2,4,6-trimethylbenzoyl-diphenylphosphine oxide (TPO) as a photoinitiator. By adjusting the mass ratio of AMPS to BA to 3:7, continuously react for 2 hours under magnetic stirring (800 rpm, 40 °C) to form a uniform transparent solution.

[0032] 2. Immerse the silicone rubber substrate ultrasonically cleaned with an acetone-ethanol mixed solution and pretreated with oxygen plasma vertically into the pre-gel system at a constant rate of 5 cm / min, and keep it for 5 min to ensure that the solution fully infiltrates the surface microstructure of the substrate; then irradiate it vertically with a 365 nm wavelength ultraviolet light source (500 mW / cm 2 ) for 10 min to initiate the photopolymerization reaction of the monomers to form a three-dimensional crosslinked network; finally, transfer the sample to a vacuum drying oven and continuously dry it at a constant temperature of 80 °C for 8 h to completely remove the residual solvent and enhance the interfacial bonding force between the coating and the substrate.

[0033] 3. Immerse the sample in a 10 wt% NaOH aqueous solution at 25 °C for 30 min to fully convert the sulfonic acid groups (-SO3H) in the polymer network into the sodium salt form (-SO3Na); then perform three-level washing treatments in sequence - ① ultrasonic cleaning at 40 kHz for 5 min to remove physically adsorbed ions on the surface, ② constant-flow rinsing with deionized water 2 times, ③ centrifugal dehydration at 800 rpm and then vacuum drying at 60 °C for 2 h

[0034] 4. Immerse the sample in a 0.05 wt% AgNO 3 aqueous solution at 25 °C for 20 min, and use the substitution reaction between the sodium sulfonate group (-SO3Na) and Ag + to achieve the directional loading of silver ions; then perform three-level washing treatments in sequence - ① ultrasonic cleaning at 40 kHz for 5 min to remove unbound ions, ② constant-flow rinsing with deionized water 3 times, ③ nitrogen purging and then vacuum drying at 40 °C in the dark for 4 h. Finally, obtain the Poly(AMPS-co-BA)-Ag silver-containing modified coating.

[0035] Characterization of the modified coating:

[0036] Perform surface morphology analysis on Poly(AMPS-co-BA)-Na and Poly(AMPS-co-BA)-Ag by scanning electron microscopy (SEM) (append Figure 1)。The Poly(AMPS-co-BA)-Na coating exhibits a uniformly distributed microporous structure; after silver ion replacement, the micropores of Poly(AMPS-co-BA)-Ag are filled with silver ions, and the pore size is significantly reduced to the submicron level, indicating that the ion exchange process effectively regulates the microstructure of the coating.

[0037] Fourier transform infrared spectroscopy (FTIR) analysis shows (attached Figure 2 ) that the Poly(AMPS-co-BA) coating shows characteristic absorption peaks at 2955 cm -1 and 2870 cm -1 , corresponding to the stretching vibrations of -CH 3 and -CH 2 - in butyl acrylate, respectively. And with the increase of the BA content, the characteristic peaks become more obvious, confirming that the BA monomer has successfully participated in the copolymerization reaction. X-ray photoelectron spectroscopy (XPS) characterization shows (attached Figure 3 ) that the Poly(AMPS-co-BA)-Ag coating shows an Ag 3d5 / 2 characteristic peak at 368.1 eV. Comparing the binding energy position with the standard values of Ag 0 (368.2 eV) and Ag 2 O (367.8 eV), it is confirmed that silver exists stably in the polymer network in the ionic state (Ag + ), verifying the effectiveness of the surface modification process.

[0038] Example 2

[0039] Preparation of the antibacterial medical catheter coating:

[0040] Using a method similar to that of Example 1, the substrate is replaced from an SR silicone rubber sheet to a medical silicone catheter. First, the medical silicone catheter is immersed in a pre-prepared AMPS / BA mixed pre-gel transparent solution (AMPS:BA = 3:7, containing 0.6 mol% MBA cross-linking agent) at a constant rate of 2 cm / s for 2 min to ensure that the solution fully infiltrates the surface structure of the substrate; then, under a nitrogen protection environment, a 365 nm ultraviolet light source (500 mW / cm 2)Irradiate vertically for 10 min to induce the formation of a three-dimensional cross-linked network structure; transfer the initially cured sample to an 80 °C vacuum drying oven and treat it for 6 h to completely volatilize the solvent and densify the coating. Perform step-by-step ion functionalization on the cured substrate: ① In the sodium ionation treatment stage, immerse it in a 10 wt% NaOH solution at a constant temperature of 25 °C for 30 min, and simultaneously apply 40 kHz ultrasonic assistance (power 100 W) to enhance ion penetration; ② In the silver ion replacement stage, transfer it to a 0.05 wt% AgNO3 solution and treat it for 20 min to achieve the directional distribution of silver ions in the coating thickness direction through concentration regulation. Finally, after three-stage washing (ultrasonic cleaning → constant-flow rinsing with deionized water → nitrogen purging) and light-shielded constant-flow drying (25 °C, nitrogen flow rate 5 L / min, 12 h), the antibacterial medical catheter coating SR-Ag is obtained.

[0041] Characterization of the antibacterial medical catheter coating:

[0042] The water contact angle of the SR-F coating was measured by the sessile drop method (25 °C, 50% RH) (as shown in the appendix Figure 4 ). The contact angle of the modified coating reached 70° ± 2.5°, which was significantly lower than that of the unmodified silicone substrate (105° ± 3.2°). This change in wettability is attributed to the synergistic effect of the hydrophilic properties of the sulfonic acid groups and the surface micro-nano structure. The change in contact angle confirms that the SR-Ag coating successfully endows the material with amphiphilic characteristics - the hydrophilic surface region promotes the dissolution of silver ions, while the hydrophobic region inhibits biofilm formation. This micro-region regulation characteristic provides an interfacial basis for the antibacterial-antifouling synergistic effect.

[0043] Example 3

[0044] Antibacterial test:

[0045] In this experiment, 106 CFU / mL was selected to verify the antibacterial activity of SR-Ag against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) at different culture times. Rinse the coated catheter material with PBS, dry it, and place it in a laminar flow hood for ultraviolet sterilization for 2 h. Place the coated catheter material in a petri dish, take 20 μL of the bacterial solution and drop it on the surface of the antibacterial coated catheter, and then cover the bacterial solution with a 0.5 cm × 0.5 cm sterilized PE sheet. Since a certain humidity condition is required for the bacterial solution culture environment, a bottle cap containing sterilized normal saline needs to be placed in the petri dish and cultured in a constant temperature incubator for a specific time. Take out the coated catheter material and place it in a small beaker containing 2 mL of PBS solution for ultrasonic treatment for 2 min to disperse the attached bacteria in the solution. Take 50 μL of the solution in the small beaker and spread it on a solid medium, and then place it in a constant temperature incubator for culture. In the blank control group, 20 μL of the bacterial solution was added to the PBS solution, and then 50 μL of the bacterial solution was taken and spread on the solid medium, and the remaining steps were repeated as above.

[0046] Antibacterial test characterization:

[0047] As shown in the Figure 5 appendix, the antibacterial effects of the SR-Ag coating against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were evaluated by the agar diffusion method and the colony counting method. The experimental results showed that when the contact time reached 30 min, the antibacterial rates of both pathogens exceeded 99%, indicating that the release of Ag+ gradually exerted an antibacterial effect. This experiment verified that SR-Ag has good antibacterial properties.

Claims

1. Preparation of a silver ion modified antibacterial medical catheter coating.

2. The preparation method of a silver ion modified antibacterial medical catheter coating according to claim 1, characterized in that: AMPS was modified by introducing BA to form a Poly(AMPS-co-BA) polymer film containing sulfonic acid groups.

3. The preparation of a silver ion modified antibacterial medical catheter coating according to claim 2, characterized in that: By immersing the Poly(AMPS-co-BA) polymer film in a NaOH aqueous solution, Na+ is grafted onto the polymer through ion exchange, and Poly(AMPS-co-BA)-Na is formed through sodium ionization.

4. The preparation of a silver ion modified antibacterial medical catheter coating according to claim 3, characterized in that: By immersing the Poly(AMPS-co-BA)-Na polymer film in an AgNO3 aqueous solution, Ag+ is introduced to form Poly(AMPS-co-BA)-Ag through replacement.

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