Preparation method of antibacterial coating material based on synergistic interaction of antibiotics and metal ions as well as product and application of antibacterial coating material

Abstract

The invention discloses a preparation method of an antibacterial coating material based on synergistic interaction of antibiotics and metal ions. The preparation method comprises the following steps: (1) blending antibiotics, soluble salts of metal ions, an absorbable polymer and a mixed solvent to obtain a coating solution; the antibiotics are selected from rifampicin and minocycline hydrochloride; the metal ions are selected from Zn and / or Cu; the mixed solvent is selected from hexafluoroisopropanol and a methanol / aqueous solution, and the volume ratio of hexafluoroisopropanol in the mixed solvent is not less than 25%; and (2) uniformly spraying the coating solution on the surface of the degradable base material through ultrasonic spraying, and then carrying out drying treatment. The preparation method is easy and convenient to operate, the obtained coating is tightly combined with a degradable base material, and the antibacterial rate can still reach 90% or above after 50 times of washing. According to the prepared antibacterial coating material, the synergistic release mode of rapid sterilization and long-acting bacteriostasis is achieved through raw material screening and process optimization, and the short-term and long-acting antibacterial performance can be remarkably improved.

Description

Technical Field

[0001] This invention relates to the technical field of biomedical materials, and in particular to a method for preparing an antibacterial coating material based on the synergistic effect of antibiotics and metal ions, as well as its products and applications. Background Technology

[0002] Medical devices play a vital role in medical practice, but the bacterial infections they cause remain a serious challenge. Implantable medical devices, such as artificial joints, pacemakers, and artificial valves, are particularly vulnerable due to their prolonged contact with human tissue, making them ideal carriers for bacterial adhesion. Studies have shown that biofilm formation on the surface of medical devices is a major cause of infection, and the presence of biofilms significantly enhances bacterial resistance, making infections difficult to eradicate. Furthermore, biofilm-related infections not only increase patient suffering but also lead to exorbitant medical costs. Clinical data shows that in the United States alone, the additional medical expenses caused by implantable medical device infections amount to billions of dollars annually [Mcverry B,Polasko A, Rao E, et al. A readily scalable, clinically demonstrated, antibiofoulingzwitterionic surface treatment for implantable medical devices[J]. Advanced Materials, 2022, 34(20):2200254.]. This not only causes immense physical and psychological suffering for patients but also results in high medical costs.

[0003] With the rapid development of medical technology, biomaterials science, and the demand for antibacterial agents, antibacterial coating materials have demonstrated significant application value in medical devices, wound dressings, and tissue engineering. Traditional antibacterial coatings typically employ metal ion (such as silver, copper, and zinc) antibacterial systems. From an antibacterial perspective, metal ion-based antibacterial coatings exhibit significant antibacterial properties due to the strong bactericidal ability of the released silver, copper, and other metal ions. However, these coatings suffer from poor long-term stability, and excessive application may trigger local inflammatory responses, thereby affecting their biocompatibility.

[0004] For example, Chinese patent document CN105461952A discloses a method for preparing an antibacterial coating, in which a dopamine hydrochloride solution and a silver nitrate solution are spin-coated onto the surface of a substrate in sequence, and an antibacterial coating containing nano-silver is prepared by layer-by-layer assembly combined with ultraviolet reduction technology. Although the steps are simplified, the long-term stability and potential toxicity of nano-silver still need to be verified.

[0005] Rifampin and minocycline are both antibiotics widely used in humans as antibacterial agents. Rifampin achieves rapid bactericidal action by inhibiting bacterial transcription and is a core drug in the treatment of tuberculosis. Minocycline exerts a broad-spectrum antibacterial effect by blocking protein synthesis and is particularly suitable for skin and soft tissue infections and atypical pathogen infections. The two have different mechanisms, and long-term use of either one can easily lead to drug resistance, thus affecting the antibacterial effect.

[0006] Existing absorbable biomaterials (such as polylactic acid, glycolide / lactide copolymer, polyhydroxybutyrate, etc.) have been used in sutures, bone repair materials, and antibacterial coating materials.

[0007] For example, Chinese patent document CN117860950A discloses an antibacterial coating gel, the raw materials of which include antibacterial agents, stearate, glycolide / lactide copolymer, polyhydroxybutyrate, and organic solvents. The preparation system of this coating gel may limit biocompatibility, and the preparation process involves multiple heating and reflux steps, which is highly complex and difficult to industrialize.

[0008] In addition, existing absorbable antimicrobial coatings generally face the following challenges:

[0009] a) The antibacterial effect is not durable and is easily lost due to the rapid release of antibacterial agents;

[0010] b) Insufficient adhesion between the coating and the material, causing antibiotics to easily peel off;

[0011] c) Its antibacterial ability is relatively singular and has certain limitations; it is difficult to achieve a balance between safe and long-lasting antibacterial properties.

[0012] Therefore, developing a synergistic sustained-release antibacterial technology is particularly important for improving antibacterial performance. Summary of the Invention

[0013] To address the shortcomings of existing technologies, this invention discloses a method for preparing an antibacterial coating material based on the synergistic effect of antibiotics and metal ions. The preparation method is simple to operate, and the obtained coating is tightly bonded to the biodegradable substrate. After 50 washes, the antibacterial rate can still reach more than 90%. The prepared antibacterial coating material achieves a synergistic release mode of "rapid sterilization-long-term antibacterial effect" through raw material selection and process optimization, which can significantly improve short-term and long-term antibacterial performance.

[0014] The specific technical solution is as follows:

[0015] A method for preparing an antibacterial coating material based on the synergistic effect of antibiotics and metal ions, comprising:

[0016] (1) A coating solution is obtained by mixing antibiotics, soluble salts of metal ions, absorbable polymers and a mixed solvent;

[0017] The antibiotic was selected from rifampin and minocycline hydrochloride;

[0018] The metal ions are selected from Zn²⁺ and / or Cu²⁺;

[0019] The absorbable polymer is selected from one or more of polyglycolic acid, polylactide, polyglycolic acid-co-lactide, polyglycolic acid-co-caprolactone, and tyrosine polyarylate.

[0020] The mixed solvent is selected from hexafluoroisopropanol and methanol / water solution, and the volume percentage of hexafluoroisopropanol in the mixed solvent is not less than 25%.

[0021] (2) The coating solution is uniformly sprayed onto the surface of the biodegradable substrate by ultrasonic spraying, and then dried to obtain the antibacterial coating material based on the synergistic effect of antibiotics and metal ions.

[0022] This invention discloses a method for preparing an antibacterial coating that synergistically enhances the effects of antibiotics and metal ions. It is anticipated that through innovative material combinations and process design, the following technological breakthroughs will be achieved:

[0023] This invention utilizes highly biocompatible absorbable polymers and combines novel antibacterial agents with traditional ones, achieving excellent results across different release rates and durations, meeting the requirements of both short-term, high-efficiency release and long-term, continuous antibacterial action. A simple coating preparation technology (ultrasonic spraying) has been developed to lower the production threshold and adapt to large-scale manufacturing needs. In summary, this invention aims to fill the gaps in existing absorbable antibacterial coating materials regarding preparation processes, antibacterial durability, and synergistic effects with different antibacterial agents, providing a multifunctional, low-cost novel coating solution for the medical, bioengineering, and other fields, possessing significant technological value and market potential.

[0024] The preparation method disclosed in this invention uses two antibiotics, rifampin and minocycline, combined with the antibacterial properties of zinc and / or copper ions. An absorbable polymer is used as a drug carrier. The antibiotics and absorbable polymer are dissolved in a mixed solvent composed of hexafluoroisopropanol and methanol / water solution. Then, taking advantage of the swelling properties of this specially composed mixed solvent on the surface of a biodegradable substrate, atomized antibacterial agent particles are uniformly and stably fixed on the surface of the biodegradable substrate through an ultrasonic spraying process. At the same time, the atomized particles are insufficient to damage the surface of the substrate. By using ultrasonic spraying and the inherent properties of the solvent, the antibacterial agent and absorbable polymer are embedded in the surface of the biodegradable substrate, thus preparing an absorbable antibacterial material with sustained-release antibiotics. The process is simple, can be mass-produced, and has a more significant price advantage.

[0025] Experiments have shown that if the hexafluoroisopropanol solvent in the mixed solvent of this invention is replaced with acetonitrile or other common solvents in the art, such as tetrahydrofuran, the antibiotics will detach from the surface of the biodegradable substrate, and stable antibacterial effect cannot be achieved.

[0026] In step (1):

[0027] Preferably, the mass ratio of rifampicin to minocycline hydrochloride in the antibiotic is (0.3~3.0):1; more preferably 1:1.

[0028] Preferably, the mass ratio of antibiotic to soluble salt of metal ion is (1~6):1; further preferably (1~3):1; even more preferably (2~3):1, and most preferably 2:1.

[0029] The soluble salts of the metal ions are selected from common types such as acetates and chlorides of the metal ions.

[0030] Experiments have shown that the proportion of absorbable polymer in the raw material has a significant impact on the release rate and antibacterial durability of antibiotics. Preferably, the mass ratio of antibiotic to absorbable polymer is 1:(1~3); more preferably 1:(1.5~2.5); and even more preferably 1:1.5.

[0031] In step (1):

[0032] Preferably, the concentration of antibiotic in the coating solution is (0.5~1.5) wt%; more preferably 1 wt%.

[0033] Preferably, the volume percentage of hexafluoroisopropanol in the mixed solvent is 25-75%; more preferably 50%.

[0034] Preferably, the concentration of the methanol / water solution is 40-60 wt%; more preferably 50 wt%.

[0035] In step (2), the ultrasonic spraying:

[0036] The coating solution is filtered using an organic filter head and transferred to a syringe. The syringe is then fixed to an injection pump and connected to an ultrasonic nozzle via a polytetrafluoroethylene tube.

[0037] Preferably, the spraying flow rate is 0.2~0.4 mL / min, the number of sprays is 4~8, the feed speed is 6~10 mm / s, and the nozzle height is 30~50 mm.

[0038] Further optimizations were made regarding the following parameters: spray flow rate: 0.4 mL / min, number of sprays: 4, feed rate: 10 mm / s, and nozzle height: 30 mm.

[0039] Preferably, the biodegradable substrate is selected from one or more of the following: polyglycolic acid filament, polyglycolic acid nonwoven fabric, polylactide filament, polylactide nonwoven fabric, polyglycolic acid-co-lactide filament, polyglycolic acid-co-lactide nonwoven fabric, polyglycolic acid-co-caprolactone filament, and polyglycolic acid-co-caprolactone nonwoven fabric.

[0040] Preferably, the drying process is carried out at room temperature, in the dark, under vacuum.

[0041] This invention also discloses an antibacterial coating material prepared according to the above method, based on the synergistic effect of antibiotics and metal ions. This antibacterial coating material possesses a long-lasting antibacterial mechanism characterized by the rapid release of one antibiotic and the slow release of another antibiotic through a chelate formation with metal ions. This characteristic ensures that the material rapidly forms a high-concentration antibacterial environment in the initial stages of application, achieving rapid inhibition of the target pathogenic bacteria; while the other antibiotic exhibits a differentiated slow-release characteristic, with its cumulative drug release over 48 hours remaining stably within the range of 25% to 57%, forming a synergistic release mode of "rapid sterilization - long-lasting bacteriostasis".

[0042] The present invention also discloses an implantable medical device, comprising a medical device and the aforementioned antibacterial coating material based on the synergistic effect of antibiotics and metal ions, which is wrapped around the outer surface of the medical device.

[0043] The medical device is selected from cardiac pacemakers, artificial heart valves, vascular stents, defibrillators, or spinal cord stimulators.

[0044] Compared with the prior art, the present invention has the following beneficial effects:

[0045] This invention focuses on improving the antibacterial properties of medical devices to address the serious challenges posed by bacterial infections in the current medical field. Through systematic exploration of material modification strategies and surface coating technologies, several methods with potential application value have been successfully developed. This technology constructs a composite antibacterial system with both high binding stability and controllable sustained release through the chelation of minocycline and metal ions. This not only overcomes the performance limitations of single antibacterial components but also fills the technological gap in antibacterial coating materials for long-term repeated use. It provides a high-performance solution for fields such as medical devices and textiles that have a rigid demand for long-lasting antibacterial effects, demonstrating significant innovation, practicality, and industrial application value, fully reflecting the technological creativity and market competitiveness of this invention. Attached Figure Description

[0046] Figure 1 The in vitro release curves of rifampicin in PBS buffer are shown on the surface of the antibacterial coating materials prepared in Examples 1-3 and Comparative Example 1, respectively.

[0047] Figure 2The in vitro release curves of minocycline hydrochloride on the surface of the antibacterial coating materials prepared in Examples 1-3 and Comparative Example 1 in PBS buffer are shown.

[0048] Figure 3 The in vitro release curves of rifampicin in PBS buffer are shown for the antibacterial coating materials prepared in Example 4 and Comparative Example 5, respectively.

[0049] Figure 4 The images show the in vitro release curves of minocycline hydrochloride from the surface of the antibacterial coating materials prepared in Example 4 and Comparative Example 5 in PBS buffer. Detailed Implementation

[0050] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased commercially. The features and performance of the present invention will be further described in detail below with reference to the embodiments.

[0051] Example 1

[0052] 1) Rifampicin, minocycline hydrochloride, anhydrous zinc acetate (Zn(CH3COO)2), and polyglycolic acid (PGA) were dissolved in a mixed solution of hexafluoroisopropanol and 50% methanol / water solution (volume ratio 1:1). The solution was stirred at 45°C under light-protected conditions until completely dissolved to obtain the coating solution. The mass ratio of rifampicin, minocycline hydrochloride, anhydrous zinc acetate (Zn(CH3COO)2), and PGA was 3:3:1:9, and the total concentration of antibiotics in the coating solution was 1 wt%.

[0053] 2) After filtering the above coating solution through an organic filter head, transfer it to a syringe and adjust the ultrasonic spraying process parameters (spraying flow rate: 0.4 mL / min, spraying times: 4 times, feed speed 10 mm / s, nozzle height 30 mm) to uniformly and stably spray the coating solution onto the surface of the PLGA nonwoven fabric.

[0054] 3) Transfer the sprayed material to a vacuum drying oven and dry it under vacuum conditions at room temperature for 10 hours to obtain the antibacterial coating material.

[0055] Example 2

[0056] The preparation process is basically the same as in Example 1, with the only difference being:

[0057] In step 1), the mass ratio of rifampicin, minocycline hydrochloride, anhydrous zinc acetate (Zn(CH3COO)2) and PGA is replaced with 3:3:2:9, and the total concentration of antibiotics in the resulting coating solution remains unchanged.

[0058] Example 3

[0059] The preparation process is basically the same as in Example 1, with the only difference being:

[0060] In step 1), the mass ratio of rifampicin, minocycline hydrochloride, anhydrous zinc acetate (Zn(CH3COO)2) and PGA is replaced with 1:1:1:3, and the total concentration of antibiotics in the resulting coating solution remains unchanged.

[0061] Example 4

[0062] The preparation process is basically the same as in Example 3, with the only difference being:

[0063] In step 1), the mass ratio of rifampicin, minocycline hydrochloride, anhydrous zinc acetate (Zn(CH3COO)2) and PGA is replaced with 1:1:1:5, and the total concentration of antibiotics in the resulting coating solution remains unchanged.

[0064] Comparative Example 1

[0065] The preparation process is basically the same as in Example 1, with the only difference being:

[0066] In step 1), no anhydrous zinc acetate was added, and the mass ratio of rifampicin, minocycline hydrochloride, and PGA was 1:1:3, so the total concentration of antibiotics in the resulting coating solution remained unchanged.

[0067] Comparative Example 2

[0068] The preparation process is basically the same as in Example 1, with the only difference being:

[0069] In step 1), rifampin and minocycline hydrochloride were not added, and the mass ratio of anhydrous zinc acetate to PGA was replaced with 1:9.

[0070] Comparative Example 3

[0071] The preparation process is basically the same as in Example 1, with the only difference being:

[0072] In step 1), the mixed solvent is replaced with a mixed solution consisting of acetonitrile and 50% methanol / water solution (volume ratio 1:1), while the concentration of antibiotics in the coating solution remains unchanged.

[0073] Comparative Example 4

[0074] The preparation process is basically the same as in Example 1, with the only difference being:

[0075] In step 1), the mixed solvent is replaced with a mixed solution consisting of tetrahydrofuran and 50% methanol aqueous solution (volume ratio 1:1), while the concentration of antibiotics in the coating solution remains unchanged.

[0076] Comparative Example 5

[0077] The preparation process is basically the same as in Example 3, with the only difference being:

[0078] In step 1), the mass ratio of rifampicin, minocycline hydrochloride, anhydrous zinc acetate (Zn(CH3COO)2) and PGA is replaced with 1:1:1:1, and the total concentration of antibiotics in the resulting coating solution remains unchanged.

[0079] Performance testing:

[0080] I. Detection of antibiotics on the surface of antibacterial coating materials

[0081] High performance liquid chromatography (HPLC) conditions: Column: C18 column; Mobile phase: Methanol:acetonitrile:0.075 mol / L potassium dihydrogen phosphate solution:1 mol / L citric acid (30:30:36:4) as the mobile phase, pH adjusted to approximately 7 with 10 mol / L NaOH; Detection wavelength: 254 nm; Injection volume: 10 µL.

[0082] Method for establishing standard curves (methanol / water solution) for rifampin and minocycline hydrochloride: Weigh 10 mg of minocycline hydrochloride and rifampin separately on an electronic balance and place them in centrifuge tubes. Add them to a mixed solution of methanol and deionized water (volume ratio 1:1), stir to dissolve, and prepare a solution with a mass concentration of 1 mg / mL. Quantitatively dilute the solution to the following mass concentrations: 0.5, 1, 5, 10, 15, 20 µg / mL. Detect the absorbance values ​​of minocycline hydrochloride and rifampin at 254 nm and plot the standard curves.

[0083] Method for establishing standard curves (PBS solution) for rifampin and minocycline hydrochloride: Weigh 10 mg of minocycline hydrochloride and rifampin separately on an electronic balance and place them in centrifuge tubes. Add PBS buffer solution (pH=7.4), stir to dissolve, and prepare a solution with a mass concentration of 1 mg / mL. Quantitatively dilute the solution to the following mass concentrations: 0.5, 1, 5, 10, 15, 20 µg / mL. Detect the absorbance values ​​of minocycline hydrochloride and rifampin at 254 nm and plot the standard curves.

[0084] 1.1 In vitro release assay of rifampin and minocycline hydrochloride:

[0085] The antibacterial coating material was cut into 1x1 cm sheets, weighed, and placed in 20 mL of PBS buffer solution (pH=7.4). The sheets were then shaken at 110 rpm in a 37°C incubator. Samples were taken periodically, and the drug concentration released into the medium was determined by high-performance liquid chromatography (HPLC) at 0.5 h, 2 h, 8 h, 24 h, and 48 h. After each sampling, the buffer solution was replaced with 15 mL, 10 mL, 5 mL, and 2 mL of fresh buffer solution to maintain a concentration detectable by the instrument. The percentage of drug release at different time points was determined according to a standard curve.

[0086] In the antibacterial coating materials prepared in Examples 1-4 and Comparative Examples 1 and 5 of this invention, the loading of the two key antibacterial active ingredients (rifampicin and minocycline hydrochloride) on the surface showed high uniformity. Precise detection confirmed that their content was stably controlled within the range of 110±2 µg / cm². This loading level not only ensured the consistency of the initial antibacterial activity of the material, but also reflected the precise controllability of the coating preparation process of this invention, laying a core foundation for the stable performance of subsequent drug release.

[0087] The in vitro release kinetics curves of the two antibiotics in the antibacterial coating materials prepared in Examples 1-3 and Comparative Example 1 are shown below. Figure 1 (Rifampin) and Figure 2 (Minocycline hydrochloride) As shown in the figure, the horizontal axis represents the release time, in hours (h). Among the antibacterial coating materials prepared in Examples 1-3, rifampicin exhibits rapid and efficient release behavior with little difference in release rate. Within a 48-hour in vitro release period, its cumulative drug release can reach over 70%. This characteristic ensures that the material quickly forms a high-concentration antibacterial environment in the early stages of application, achieving rapid inhibition of the target pathogenic bacteria. Minocycline, on the other hand, exhibits a differentiated slow release characteristic, with its cumulative drug release within the 48-hour range remaining stable at 25%-57%, forming a synergistic release mode of "rapid sterilization - long-lasting bacteriostasis." This innovative release behavior is one of the core technical highlights that distinguishes this invention from traditional single antibacterial coating materials. In contrast, the antibacterial coating material prepared in Comparative Example 1 shows consistent release rates for rifampicin and minocycline hydrochloride, with a cumulative release of approximately 74% within 48 hours, showing no difference in release rate.

[0088] Further research revealed a significant correlation between the slow-release characteristics of minocycline hydrochloride and the zinc ion content in the coating system. The mechanism of action involves minocycline hydrochloride coordinating with zinc ions to form a stable chelate. This chelate effectively reduces the release rate of minocycline hydrochloride in the release medium, thereby regulating its release rate and achieving long-acting release. This long-acting release mode avoids excessively high drug concentrations in local tissues, reducing side effects such as local irritation and drug resistance risks caused by sudden increases in drug concentration. This achieves synergistic optimization of efficacy and safety, demonstrating the innovation and application advantages of the material in the field of medical antibacterial applications.

[0089] The in vitro release kinetic curves of the two antibiotics in the antibacterial coating materials prepared in Example 4 and Comparative Example 5 are shown below. Figure 3 (Rifampin) and Figure 4 As shown in (minocycline hydrochloride), the proportion of polymer also has a significant impact on the release rate of antibiotics. When the polymer concentration is low (Comparative Example 5), it cannot effectively encapsulate the antibiotic, resulting in an excessively fast release rate. When the polymer concentration is too high, the antibiotic is almost completely encapsulated, and the thicker coating with lower porosity results in an extremely slow release rate.

[0090] II. Antibacterial Performance Test

[0091] Sample preparation: The antibacterial coating materials prepared in each example and comparative example were cut into 2cm×2cm sheet samples and sterilized by ultraviolet light radiation.

[0092] Antibacterial rate test: Following ISO 22196-2011, Staphylococcus aureus (ATCC 6538) was inoculated at a bacterial concentration of 1×10⁻⁶. 5 CFU / mL. After the sample has been in contact with the bacterial culture for 24 hours, it is eluted and cultured for counting.

[0093] The formula for calculating the inhibition rate is: Inhibition rate = (number of colonies in the blank group - number of colonies in the sample group) / number of colonies in the blank group × 100%.

[0094] Long-lasting antibacterial performance test: The sample was immersed in an aqueous solution containing 1 wt% laundry detergent for 50 cycles (5 minutes each time) to repeat the antibacterial rate test.

[0095] The antibacterial rate test results of each sample under different washing cycles are shown in Table 1.

[0096] Table 1

[0097]

[0098] As shown in Table 1, the antibacterial coating material prepared in this invention maintains an antibacterial rate of over 90% after 50 standard washing cycles, demonstrating excellent antibacterial durability. In stark contrast, the antibacterial performance of Comparative Example 2 shows a more significant decline. The antibacterial performance of a single zinc ion is inherently weak; after only 25 washes, the antibacterial rate drops to 0, indicating a complete loss of antibacterial ability. This phenomenon can be attributed to the use of only a single metal ion as the antibacterial component in Comparative Example 2. Due to the physical property of metal ions being easily soluble in water, they are thoroughly washed away with the washing liquid during repeated washing, leading to the failure of the antibacterial function. Furthermore, comparative testing of the antibacterial coating material containing only a single antibiotic prepared in Comparative Example 1 revealed a significant decrease in its antibacterial rate after multiple washes. The main reason for this is that the single antibiotic lacks a stable binding mechanism in the coating system, resulting in rapid and large-scale release during washing. This leads to a sharp decrease in the effective content of the antibacterial agent within the coating, ultimately causing a significant decline in antibacterial performance. The antibacterial coating materials prepared in Comparative Examples 3 and 4 lacked a swelling mechanism with the substrate due to the solvents used, resulting in weak adhesion between the coating and the substrate. After repeated washing, their antibacterial properties decreased significantly, and they lacked long-lasting antibacterial activity. The antibacterial coating prepared in Comparative Example 5 showed an even more pronounced decrease in antibacterial performance after washing, mainly due to its lower polymer concentration and less encapsulation of the antibacterial agent, making it easier to wash away. In contrast, the antibacterial coating material used in this invention, which utilizes the synergistic effect of antibiotics and metal ions, maintained a good antibacterial rate (≥90%) even after 50 washes.

[0099] The test results fully demonstrate that the composite antibacterial system formed by the chelation of minocycline hydrochloride (antibiotic) and metal ions can significantly improve the binding stability and controlled release of antibacterial components in the coating, effectively avoiding the defects of easy loss and rapid release of single antibacterial components. This results in coatings with more durable and superior antibacterial properties, providing key technical support for the long-term application of antibacterial coating materials.

[0100] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. The specific examples used above to illustrate the present invention are only for the purpose of helping to understand the present invention and are not intended to limit the present invention. Those skilled in the art to which this invention pertains can make several simple deductions, modifications, substitutions, or combinations based on the concept of the present invention. These deductions, modifications, substitutions, or combinations also fall within the scope of the claims of the present invention.

Claims

1. A method for preparing an antibacterial coating material based on the synergistic effect of antibiotics and metal ions, characterized in that, include: (1) A coating solution is obtained by mixing antibiotics, soluble salts of metal ions, absorbable polymers and a mixed solvent; The antibiotic was selected from rifampin and minocycline hydrochloride; The metal ions are selected from Zn²⁺ and / or Cu²⁺; The absorbable polymer is selected from one or more of polyglycolic acid, polylactide, polyglycolic acid-co-lactide, polyglycolic acid-co-caprolactone, and tyrosine polyarylate. The mixed solvent is selected from hexafluoroisopropanol and methanol / water solution, and the volume percentage of hexafluoroisopropanol in the mixed solvent is not less than 25%. (2) The coating solution is uniformly sprayed onto the surface of the biodegradable substrate by ultrasonic spraying, and then dried to obtain the antibacterial coating material based on the synergistic effect of antibiotics and metal ions.

2. The method for preparing the antibacterial coating material based on the synergistic effect of antibiotics and metal ions according to claim 1, characterized in that, In step (1): In the antibiotic, the mass ratio of rifampin to minocycline hydrochloride is (0.3~3.0):1; The mass ratio of antibiotics to soluble salts of metal ions is (1~6):1; The mass ratio of antibiotic to absorbable polymer is 1:(1~3).

3. The method for preparing the antibacterial coating material based on the synergistic effect of antibiotics and metal ions as described in claim 2, characterized in that, The mass ratio of antibiotics to soluble salts of metal ions is (1~3):

1.

4. The method for preparing the antibacterial coating material based on the synergistic effect of antibiotics and metal ions according to claim 1, characterized in that, In step (1): The concentration of antibiotics in the coating solution is (0.5~1.5) wt% In the mixed solvent, hexafluoroisopropanol accounts for 25-75% by volume; The concentration of the methanol / water solution is 40~60 wt%.

5. The method for preparing the antibacterial coating material based on the synergistic effect of antibiotics and metal ions according to claim 1, characterized in that, In step (2), the ultrasonic spraying: The spraying flow rate is 0.2~0.4 mL / min, the number of sprays is 4~8, the feed speed is 6~10 mm / s, and the nozzle height is 30~50 mm.

6. The method for preparing the antibacterial coating material based on the synergistic effect of antibiotics and metal ions according to claim 1, characterized in that, In step (2): The biodegradable substrate is selected from one or more of the following: polyglycolic acid filament, polyglycolic acid nonwoven fabric, polypropylene filament, polypropylene nonwoven fabric, polyglycolic acid-co-propylene filament, polyglycolic acid-co-propylene nonwoven fabric, polyglycolic acid-co-caprolactone filament, and polyglycolic acid-co-caprolactone nonwoven fabric.

7. The method for preparing the antibacterial coating material based on the synergistic effect of antibiotics and metal ions according to claim 1, characterized in that, In step (2): The drying process is carried out at room temperature, in the dark, and under vacuum.

8. An antibacterial coating material based on the synergistic effect of antibiotics and metal ions prepared by the method according to any one of claims 1 to 7.

9. An implantable medical device, characterized in that, Includes medical devices and an antibacterial coating material based on the synergistic effect of antibiotics and metal ions, as described in claim 8, which is wrapped around the outer surface of the medical devices.

10. The implantable medical device according to claim 9, characterized in that, The medical device is selected from cardiac pacemakers, artificial heart valves, vascular stents, defibrillators, or spinal cord stimulators.

Images