Antibacterial coating, preparation method and application thereof and medical instrument

Abstract

The invention belongs to the field of antibacterial functional materials, and discloses an antibacterial coating, a preparation method and application thereof and a medical instrument. The antibacterial coating provided by the invention comprises an anionic polyelectrolyte brush and protonated organic nanoparticles, the anionic polyelectrolyte brush is connected to a substrate material through chemical bonds, and the protonated organic nanoparticles are connected to the anionic polyelectrolyte brush. The antibacterial coating has excellent sterilization function, biocompatibility, stability, stimuli responsiveness and reusability, can be well applied to modification of the antibacterial function of medical instruments, and has wide application prospects.

Description

Technical Field

[0001] The present invention belongs to the technical field of antibacterial functional materials, and in particular relates to an antibacterial coating, a preparation method and application thereof, and a medical device. Background Art

[0002] The probability of bacterial infection during hospitalization is 6-12%, and bacterial infection may induce diseases such as wound infection, bacteremia and tissue inflammation, which not only increases the burden on patients, but may even threaten their lives in severe cases. Clinical studies have shown that the attachment, growth and construction of biofilms on the surfaces of medical devices such as central venous catheters, intravascular catheters, urinary catheters and endotracheal tubes are the main factors causing nosocomial infections, especially for the elderly, infants and pregnant women with weak immune systems. They are more susceptible to bacterial infections caused by medical devices. Therefore, it is of great significance to modify the function of medical devices to give them antibacterial properties for the prevention of bacterial infections.

[0003] At present, directly coating antibacterial substances on the base material of medical devices to form antibacterial coatings is the most commonly used method for functional modification of medical devices to give them antibacterial properties. However, the antibacterial coating prepared by this method has poor stability in combination with the base material, which makes the antibacterial properties of medical devices easily lost, which limits its use in actual clinical applications and has great limitations. Summary of the invention

[0004] The first purpose of the present invention is to solve the problem of poor stability of the antibacterial coating and the base material and easy loss of antibacterial performance in the prior art, and to provide an antibacterial coating. The antibacterial coating has excellent bactericidal function, biocompatibility, stability, stimulus responsiveness and reusability, and can be well applied to the antibacterial function modification of medical devices, with broad application prospects.

[0005] The second object of the present invention is to provide a method for preparing the above antibacterial coating.

[0006] The third object of the present invention is to provide the use of the above antibacterial coating in the preparation of antibacterial functional materials.

[0007] A fourth object of the present invention is to provide a medical device.

[0008] Specifically, the antibacterial coating provided by the present invention comprises anionic polyelectrolyte brushes and protonated organic nanoparticles, wherein the anionic polyelectrolyte brushes are connected to a substrate material via chemical bonds, and the protonated organic nanoparticles are connected to the anionic polyelectrolyte brushes.

[0009] Furthermore, the anionic polyelectrolyte brush is obtained by carrying out surface graft polymerization of unsaturated sulfonate on a substrate material.

[0010] Furthermore, the unsaturated sulfonate is selected from one or more of sodium 2-acrylamido-2-methylpropanesulfonate, sodium styrenesulfonate, sodium 2-methyl-2-propylene-1-sulfonate, sodium vinylsulfonate, sodium 3-allyloxy-2-hydroxy-1-propanesulfonate and potassium salt of 3-sulfonopropyl methacrylate.

[0011] Furthermore, the surface grafting polymerization method is selected from one or more of UV grafting, surface initiated atom transfer radical polymerization, reversible addition-fragmentation chain transfer radical polymerization, ozone grafting and plasma polymerization.

[0012] Furthermore, the surface grafting polymerization method is selected from one or more of UV grafting, surface initiated atom transfer radical polymerization, reversible addition-fragmentation chain transfer radical polymerization, ozone grafting and plasma polymerization.

[0013] Furthermore, the protonated organic nanoparticles are obtained by protonating the organic nanoparticles with a strong acid solution.

[0014] Furthermore, the strong acid solution is selected from one or more of a dilute sulfuric acid solution, a dilute hydrochloric acid solution and a dilute nitric acid solution.

[0015] Furthermore, the organic nanoparticles are selected from one or more of cross-linked polyethyleneimine nanoparticles, cross-linked polylysine nanoparticles, cross-linked chitosan nanoparticles, polytannic acid nanoparticles, polypeptide nanoparticles, peptoid nanoparticles and starch nanoparticles.

[0016] Furthermore, the substrate material is a metal material and / or an organic polymer material.

[0017] Furthermore, the metal material is selected from one or more of stainless steel, cobalt alloy, titanium alloy and magnesium alloy.

[0018] Furthermore, the organic polymer material is selected from one or more of polyurethane, polyester fiber, polyvinyl pyrrolidone, polyetheretherketone, polymethyl methacrylate, polyvinyl alcohol, polylactic acid, polyethylene and silicone.

[0019] Furthermore, the base material is polyurethane and / or silicone.

[0020] The preparation method of the above-mentioned antibacterial coating provided by the present invention specifically comprises: S1, taking the base material for activation treatment to generate olefin reaction active sites to obtain an activated base material; S2, taking unsaturated sulfonate and the activated base material for surface grafting polymerization to obtain a base material grafted with anionic polyelectrolyte brushes; S3, taking the protonated organic nanoparticles to treat the base material grafted with anionic polyelectrolyte brushes to obtain an antibacterial coating connected to the base material by chemical bonds.

[0021] Furthermore, the base material is polyurethane.

[0022] Furthermore, when the base material is polyurethane, in step S1, the activation treatment specifically includes: taking an ultraviolet light initiator to immerse the polyurethane to obtain activated polyurethane.

[0023] Furthermore, when the base material is polyurethane, in step S1, the ultraviolet light initiator is selected from one or more of benzophenone, 4-methylbenzophenone and 2,4,6-trimethylbenzophenone.

[0024] Furthermore, when the base material is polyurethane, in step S1, the concentration of the ultraviolet light initiator in the immersion treatment is 0.1-10 wt%.

[0025] Furthermore, when the base material is polyurethane, in step S1, the soaking treatment time is 5 to 30 minutes.

[0026] Furthermore, when the base material is polyurethane, in step S2, the surface graft polymerization specifically includes: applying the unsaturated sulfonate to the surface of the activated base material, and subjecting the surface to ultraviolet irradiation treatment to obtain polyurethane grafted with anionic polyelectrolyte brushes.

[0027] Furthermore, when the substrate material is polyurethane, in step S2, the amount of unsaturated sulfonate applied in the surface graft polymerization is 0.1 to 0.2 g / cm 2 .

[0028] Furthermore, when the base material is polyurethane, in step S2, the irradiation wavelength of the ultraviolet irradiation is 200-400 nm, the irradiation power is 60-120 W, and the irradiation time is 1-10 min.

[0029] Furthermore, the base material is silicone.

[0030] Furthermore, when the base material is silicone, in step S1, the activation treatment specifically includes: in an inert gas, using plasma to perform surface hydroxylation treatment on the silicone to obtain hydroxylated silicone; and using a halogenating agent to perform a halogenation reaction on the hydroxylated silicone to obtain the activated silicone.

[0031] Furthermore, when the base material is silicone, in step S1, the hydroxylation treatment time is 1 to 10 minutes.

[0032] Furthermore, when the base material is silicone, in step S1, the halogenating agent is α-bromoisobutyryl bromide and / or α-bromoisobutyryl chloride.

[0033] Furthermore, when the base material is organic silicon, in step S1, the added concentration of the halogenating agent is 0.01-1 mmol / L.

[0034] Furthermore, when the base material is silicone, in step S1, the temperature of the halogenation reaction is 0-4° C., and the time is 0.5-5 h.

[0035] Furthermore, when the base material is silicone, in step S2, the surface graft polymerization specifically includes: in the presence of cuprous salt and complexing agent, taking the activated silicone and unsaturated sulfonate for addition polymerization reaction to obtain silicone grafted with anionic polyelectrolyte brush.

[0036] Furthermore, when the base material is silicone, in step S2, the cuprous salt is cuprous chloride, and the complexing agent is 2,2′-bipyridine.

[0037] Furthermore, when the base material is silicone, in step S2, the concentration of unsaturated sulfonate added in the surface graft polymerization is 0.01-4 mmol / L, the concentration of cuprous salt added is 0.01-2 mmol / L, and the concentration of complexing agent added is 0.01-2 mmol / L.

[0038] Furthermore, when the base material is silicone, in step S2, the temperature of the addition polymerization reaction is 40 to 60° C., and the time is 1 to 20 minutes.

[0039] The present invention also provides the use of the antibacterial coating in the preparation of antibacterial functional materials.

[0040] The medical device provided by the present invention comprises the above-mentioned antibacterial coating.

[0041] Beneficial effects:

[0042] The antibacterial coating provided by the present invention comprises anionic polyelectrolyte brushes and protonated organic nanoparticles. The anionic polyelectrolyte brushes are stably connected to the base material through chemical bonds, and the protonated organic nanoparticles carry a certain amount of positive charge and can be stably connected to the anionic polyelectrolyte brushes through electrostatic effects, hydrophobic effects and other forces. The positive charge carried by the protonated organic nanoparticles can effectively capture and kill bacteria, and has excellent bactericidal function and stability. Secondly, the anionic polyelectrolyte brushes are in a curled state under non-strong alkaline conditions and have a strong interaction force with the protonated organic nanoparticles. By utilizing the anionic polyelectrolyte brushes The steric hindrance can achieve selective killing of bacteria without destroying other normal cells. The antibacterial coating has excellent biological compatibility, especially blood compatibility, and the hemolysis rate is only 0.025%. Furthermore, under strong alkaline conditions, the structure of the anionic polyelectrolyte brush stretches and the protonated organic nanoparticles are deprotonated, which gives the antibacterial coating excellent stimulus responsiveness, so that the strong alkaline environment can be used as a stimulus condition to achieve the release of dead bacteria and protonated organic nanoparticles on the antibacterial coating, and the protonated organic nanoparticles can be repeatedly fixed on the anionic polyelectrolyte brush, which has excellent reusability. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] Figure 1 This is an experimental result diagram of the antibacterial rate test of the antibacterial coating provided in Example 1 of the present invention (scale is 10 μm);

[0044] Figure 2 This is an experimental result diagram of the antibacterial rate test of the antibacterial coating provided in Example 8 of the present invention (scale is 10 μm);

[0045] Figure 3 This is an experimental result diagram of the antibacterial rate test of the antibacterial coating provided in Comparative Example 1 of the present invention (scale is 10 μm);

[0046] Figure 4 This is an experimental result diagram of the antibacterial rate test of the antibacterial coating provided in Comparative Example 2 of the present invention (scale is 10 μm);

[0047] Figure 5 This is one of the experimental result graphs of the pH stimulus responsiveness test of the antibacterial coating provided in Example 1 of the present invention (the scale is 100 μm);

[0048] Figure 6 Figure 2 is the experimental result of the pH stimulus responsiveness test of the antibacterial coating provided in Example 1 of the present invention (scale is 100 μm);

[0049] Figure 7 The third figure shows the experimental results of the pH stimulus responsiveness test of the antibacterial coating provided in Example 1 of the present invention (the scale bar is 100 μm). DETAILED DESCRIPTION

[0050] Based on the problems of poor stability and easy loss of antibacterial performance of antibacterial coatings in the prior art, the inventors of the present invention creatively discovered through extensive and in-depth research that an anionic polyelectrolyte brush connected by chemical bonds and negatively charged is constructed on a substrate material by a grafting method, and then protonated organic nanoparticles are introduced into the anionic polyelectrolyte brush by electrostatic and hydrophobic effects. The constructed antibacterial coating has a curled spatial structure under non-strong alkaline conditions, and the anionic polyelectrolyte brush and the protonated organic nanoparticles are stably combined, giving the antibacterial coating excellent stability and excellent selective killing ability for bacteria, while under strong alkaline conditions, the anionic polyelectrolyte brush structure can be stretched, and the anionic polyelectrolyte brush and the protonated organic nanoparticles can be dissociated, giving the antibacterial coating excellent stimulus responsiveness, and the stimulus responsiveness can be used to clean the antibacterial coating, release dead bacteria and organic nanoparticles, and the anionic polyelectrolyte brush can be combined with the protonated organic nanoparticles again to achieve reuse. Based on this, the technical solution of the present invention is obtained.

[0051] In the present invention, the antibacterial coating specifically comprises anionic polyelectrolyte brushes and protonated organic nanoparticles, wherein the anionic polyelectrolyte brushes are connected to the substrate material via chemical bonds, and the protonated organic nanoparticles are connected to the anionic polyelectrolyte brushes.

[0052] In the present invention, the base material is a type of material commonly used in existing medical devices, which specifically includes metal materials and / or organic polymer materials. Specific examples of the metal material include but are not limited to: one or more of stainless steel, cobalt alloy, titanium alloy and magnesium alloy. Specific examples of the organic polymer material include but are not limited to: one or more of polyurethane, polyester fiber, polyvinyl pyrrolidone, polyether ether ketone, polymethyl methacrylate, polyvinyl alcohol, polylactic acid, polyethylene and silicone.

[0053] In the present invention, the anionic polyelectrolyte brush is specifically obtained by taking unsaturated sulfonate and performing surface graft polymerization on a base material.

[0054] In the present invention, the unsaturated sulfonate refers to a class of organic compounds having unsaturated bonds such as carbon-carbon double bonds and / or carbon-carbon triple bonds and sulfonate groups in the molecular structure, and the unsaturated sulfonates are grafted and polymerized with each other and with the surface of the substrate material to form a negatively charged anionic polyelectrolyte brush on the substrate material.

[0055] In some specific embodiments, specific examples of the unsaturated sulfonate include but are not limited to: one or more of sodium 2-acrylamido-2-methylpropanesulfonate, sodium styrenesulfonate, sodium 2-methyl-2-propylene-1-sulfonate, sodium vinylsulfonate, sodium 3-allyloxy-2-hydroxy-1-propanesulfonate and potassium salt of 3-sulfonopropyl methacrylate.

[0056] In the present invention, the surface graft polymerization utilizes the reactivity of carbon-carbon double bonds and / or carbon-carbon triple bonds in the molecular structure of unsaturated sulfonates to achieve polymerization between unsaturated sulfonates and chemical bonding between them and the substrate material. Specific examples of the surface graft polymerization method include but are not limited to: one or more of ultraviolet grafting, surface-initiated atom transfer radical polymerization, reversible addition-fragmentation chain transfer radical polymerization, ozone grafting and plasma polymerization.

[0057] In the present invention, the method, steps, reagents and conditions used in the surface graft polymerization need to be selected according to the substrate material, and the surface graft polymerization method for a specific substrate material described below cannot be understood as a limitation on the anionic polyelectrolyte brush in the antibacterial coating. That is, the antibacterial coating claimed in the present invention can be but is not limited to the one prepared by the preparation method described below.

[0058] In the present invention, the protonated organic nanoparticles are obtained by protonating the organic nanoparticles with an acidic solution.

[0059] In the present invention, the acidic solution refers to a type of solution containing a strong acid as a solute, which can provide a large amount of H + To achieve protonation of organic nanoparticles, specific examples include but are not limited to: one or more of dilute sulfuric acid solution, dilute hydrochloric acid solution and dilute nitric acid solution. Wherein, the concentration of the dilute sulfuric acid solution is preferably 0.1-10 g / mL, such as 0.1 g / mL, 0.3 g / mL, 0.5 g / mL, 1 g / mL, 5 g / mL, 10 g / mL or any value therebetween. The concentration of the dilute hydrochloric acid solution is preferably 0.1-10 g / mL, such as 0.1 g / mL, 0.2 g / mL, 0.8 g / mL, 1 g / mL, 5 g / mL, 10 g / mL or any value therebetween. The concentration of the dilute nitric acid solution is preferably 0.1-10 g / mL, such as 0.1 g / mL, 0.4 g / mL, 1.8 g / mL, 3.6 g / mL, 5.9 g / mL, 8 g / mL, 10 g / mL or any value therebetween.

[0060] In the present invention, the organic nanoparticles refer to a type of particles composed of organic matter and having a size at the nanometer level. Specific examples include but are not limited to: one or more of cross-linked polyethyleneimine nanoparticles, cross-linked polylysine nanoparticles, cross-linked chitosan nanoparticles, polytannic acid nanoparticles, polypeptide nanoparticles, peptoid nanoparticles and starch nanoparticles.

[0061] Based on obtaining the above antibacterial coating, the present invention also provides a method for preparing the antibacterial coating. The preparation method specifically comprises: S1, taking the base material and performing activation treatment to generate olefin reaction active sites to obtain an activated base material; S2, taking unsaturated sulfonate and the activated base material to perform surface graft polymerization to obtain a base material grafted with anionic polyelectrolyte brushes; S3, taking the protonated organic nanoparticles and treating the base material grafted with anionic polyelectrolyte brushes to obtain an antibacterial coating connected to the base material through chemical bonds.

[0062] In the present invention, when the base material is selected as polyurethane, in step S1, the activation treatment specifically includes: taking an ultraviolet light initiator to soak the polyurethane to obtain an activated polyurethane; in step S2, the surface graft polymerization specifically includes: taking the unsaturated sulfonate and applying it to the surface of the activated base material, and performing ultraviolet irradiation treatment to obtain a polyurethane grafted with anionic polyelectrolyte brushes. Wherein, the ultraviolet light initiator refers to a class of compounds that can generate active intermediates such as free radicals or cations under the irradiation of ultraviolet light, and specific examples include but are not limited to: one or more of benzophenone, 4-methylbenzophenone and 2,4,6-trimethylbenzophenone.

[0063] In some specific embodiments, the concentration of the ultraviolet initiator in the immersion treatment is preferably 0.1-10wt%, such as 0.1wt%, 0.5wt%, 0.8wt%, 1wt%, 3wt%, 5wt%, 8wt%, 10wt% or any value therebetween. At this time, the ultraviolet initiator can fully act on the polyurethane to achieve a better activation effect, which is conducive to the subsequent formation of anionic polyelectrolyte brushes on the polyurethane.

[0064] In some specific embodiments, the soaking treatment time is preferably 5 to 30 minutes, such as 5 minutes, 8 minutes, 10 minutes, 20 minutes, 25 minutes, 30 minutes or any value therebetween. At this time, the polyurethane can be fully activated, which is beneficial to the subsequent formation of anionic polyelectrolyte brushes.

[0065] In some specific embodiments, the amount of unsaturated sulfonate applied in the surface graft polymerization is preferably 0.1 to 0.5 g / cm 2 , such as 0.1g / cm 2, 0.2g / cm 2 , 0.25g / cm 2 , 0.4g / cm 2 , 0.5g / cm 2 At this time, it is favorable to realize the reaction between the unsaturated sulfonates and between the unsaturated sulfonates and the substrate material to form an anionic polyelectrolyte brush with a suitable degree of polymerization on the polyurethane, and the polyurethane has a good anionic polyelectrolyte brush grafting rate.

[0066] In some specific embodiments, the conditions of ultraviolet irradiation include: the irradiation wavelength is preferably 200-400nm, such as 200nm, 250nm, 280nm, 300nm, 350nm, 400nm or any value therebetween; the irradiation power is preferably 60-120W, such as 60W, 80W, 90W, 100W, 120W or any value therebetween; the irradiation time is preferably 1-10min, such as 1min, 3min, 5min, 7min, 9min, 10min or any value therebetween. At this time, it is beneficial to achieve the extension of the molecular chain, so that the formed anionic polyelectrolyte brush has a suitable degree of polymerization, the formed spatial structure has a suitable spatial barrier effect and can better load protonated organic nanoparticles, so as to better achieve the selective killing effect on bacteria.

[0067] In the present invention, when the base material is selected as silicone, in step S1, the activation treatment specifically includes: in an inert gas, using plasma to perform surface hydroxylation treatment on the silicone to obtain hydroxylated silicone; using a halogenating agent to react with the hydroxylated silicone to obtain the activated silicone; in step S2, the surface graft polymerization specifically includes: in the presence of a cuprous salt and a complexing agent, using the activated silicone and an unsaturated sulfonate to perform an addition reaction to obtain silicone grafted with anionic polyelectrolyte brushes. The halogenating agent refers to a type of substance that has halogen atoms such as chlorine and bromine in its molecules and can react with hydroxyl groups. The reaction of the halogenating agent with the hydroxylated silicone allows the silicone to be modified with halogen atoms as active sites for reacting with unsaturated sulfonates; specific examples of the halogenating agent include but are not limited to: α-bromoisobutyryl bromide and / or α-bromoisobutyryl chloride. The cuprous salt refers to a substance containing Cu + A class of compounds, which are used in combination with a complexing agent to catalyze the addition reaction of activated organosilicon and unsaturated sulfonate; specific examples of the cuprous salt include but are not limited to: cuprous chloride and / or cuprous bromide. The complexing agent refers to a class of compounds that can react with Cu + A compound that forms a complex, which cooperates with a cuprous salt to catalyze the addition polymerization reaction of activated organic silicon and unsaturated sulfonate; specific examples of the complexing agent include but are not limited to: 2,2'-bipyridine.

[0068] In some specific embodiments, the hydroxylation treatment time is preferably 1 to 10 minutes, such as 1 minute, 3 minutes, 5 minutes, 8 minutes, 10 minutes or any value therebetween. At this time, hydroxyl groups can be effectively introduced on the surface of the organosilicon material to provide more reactive sites.

[0069] In some specific embodiments, the amount of the halogenating agent added is preferably 0.01-1 mmol / L, such as 0.01 mmol / L, 0.05 mmol / L, 0.08 mmol / L, 0.1 mmol / L, 0.5 mmol / L, 1 mmol / L or any value therebetween. In this case, halogen atoms can be effectively introduced onto the surface of the hydroxylated organosilicon to provide more reactive sites.

[0070] In some specific embodiments, the conditions of the halogenation reaction include: the temperature is preferably 0-4°C, such as 0°C, 0.5°C, 1°C, 2°C, 3°C, 4°C or any value therebetween; the time is preferably 0.5-5h, such as 0.5h, 0.8h, 1h, 3h, 5h or any value therebetween. At this time, the hydroxyl groups on the surface of the hydroxylated organosilicon can fully react with the halogen atoms to provide more reactive sites.

[0071] In some specific embodiments, the added concentration of the unsaturated sulfonate in the surface graft polymerization is 0.01-4mmol / L, such as 0.01mmol / L, 0.05mmol / L, 1mmol / L, 1.5mmol / L, 2mmol / L, 3mmol / L, 4mmol / L or any value therebetween; the added concentration of the cuprous salt is preferably 0.01-2mmol / L, such as 0.01mmol / L, 0.1mmol / L, 0.5mmol / L, 1.2mmol / L, 2mmol / L or any value therebetween; the added concentration of the complexing agent is preferably 0.01-2mmol / L, such as 0.01mmol / L, 0.05mmol / L, 0.1mmol / L, 0.4mmol / L, 0.8mmol / L, 1mmol / L, 1.5mmol / L, 2mmol / L or any value therebetween. At this time, it is beneficial to achieve the reaction between the unsaturated sulfonates and between the unsaturated sulfonates and the base material to form anionic polyelectrolyte brushes with a suitable degree of polymerization on the organosilicon, and the organosilicon has a good grafting rate of anionic polyelectrolyte brushes.

[0072] In some specific embodiments, the conditions of the addition polymerization reaction include: the temperature is preferably 40-60°C, such as 40°C, 41°C, 43°C, 45°C, 50°C, 53°C, 58°C, 60°C or any value therebetween; the time is preferably 1-20min; such as 1min, 1.5min, 3min, 8min, 10min, 13min, 18min, 20min or any value therebetween. At this time, it is beneficial to achieve the extension of the molecular chain, so that the formed anionic polyelectrolyte brush has a suitable degree of polymerization, the formed spatial structure has a suitable spatial barrier effect and can better load protonated organic nanoparticles, so as to better achieve the selective killing effect on bacteria.

[0073] Based on the excellent sterilization function, biocompatibility, stability, stimulus responsiveness and reusability of the antibacterial coating, the present invention also provides the use of the antibacterial coating in the preparation of antibacterial functional materials. The actual use of the antibacterial functional materials can be, but is not limited to, in the production and manufacture of medical devices.

[0074] Based on the excellent sterilization function, biocompatibility, stability, stimulus responsiveness and reusability of the antibacterial coating, the present invention also provides a medical device. The medical device includes the antibacterial coating and can effectively prevent bacterial interference caused by the intervention of the medical device.

[0075] Embodiments of the present invention are described in detail below, and the examples of the embodiments are intended to be used to explain the present invention, but should not be construed as limiting the present invention. In the embodiments, if specific techniques or conditions are not specified, the techniques or conditions described in the literature in this area or the product specifications are used. If the manufacturer is not specified for reagents or instruments used, they are all conventional products that can be obtained commercially.

[0076] The raw materials and reagents involved in the following examples and comparative examples specifically include:

[0077] Medical polyurethane (Meirui New Materials Co., Ltd., catalog number );

[0078] Medical silicone (Dow Corning, product number Liveo TM Q7);

[0079] Poly-lysine (B&K Technology Co., Ltd., catalog number 1381204);

[0080] Chitosan (B&K Technology Co., Ltd., catalog number 995947);

[0081] Tannic acid (B&K Technology Co., Ltd., catalog number 120685).

[0082] Example 1

[0083] This example is used to illustrate a method for preparing an antibacterial coating on medical polyurethane, in which an anionic polyelectrolyte brush is grafted onto the surface of medical polyurethane by ultraviolet grafting method, specifically comprising:

[0084] S1. After ultrasonically cleaning the medical polyurethane with deionized water for 3 minutes, take it out and place it in a clean room to dry for 24 hours for use; then completely immerse the medical polyurethane in a 1wt% benzophenone ethanol solution for 20 minutes, take it out and dry it in the dark to obtain activated medical polyurethane.

[0085] S2, according to 1mL / cm 2 A 0.1 g / mL aqueous solution of sodium 2-acrylamide-2-methylpropane sulfonate was uniformly added dropwise to the surface of the activated medical polyurethane, followed by irradiation under a 90 W ultraviolet lamp (wavelength of 280 nm) for 5 min to allow a graft polymerization reaction of sodium 2-acrylamide-2-methylpropane sulfonate to occur on the surface of the medical polyurethane to form an anionic polyelectrolyte brush, and then ultrasonically cleaned and dried with deionized water and ethanol in sequence to obtain a medical polyurethane grafted with anionic polyelectrolyte brushes.

[0086] S3. Completely immerse the medical polyurethane grafted with anionic polyelectrolyte brush in a hydrochloric acid aqueous solution (HCl concentration is 0.01 g / mL) including 0.01 g / mL cross-linked polylysine for 30 min, take it out and wash and dry it with deionized water to fix the cross-linked polylysine nanoparticles on the anionic polyelectrolyte brush to obtain an antibacterial coating grafted on the medical polyurethane.

[0087] Example 2

[0088] The method for preparing an antibacterial coating on medical polyurethane provided in this embodiment is basically the same as that in Example 1, except that in step S2, a 0.1 g / mL sodium styrene sulfonate aqueous solution is used instead of a 2-acrylamido-2-methylpropane sulfonate aqueous solution, and other conditions are the same, and an antibacterial coating is prepared on the surface of the medical polyurethane.

[0089] Example 3

[0090] The method for preparing an antibacterial coating on medical polyurethane provided in this embodiment is basically the same as that in Example 1, except that in step S2, a 0.1 g / mL sodium vinyl sulfonate aqueous solution is used instead of a 2-acrylamido-2-methylpropane sulfonate aqueous solution, and other conditions are the same, and an antibacterial coating is prepared on the surface of the medical polyurethane.

[0091] Example 4

[0092] The method for preparing an antibacterial coating on medical polyurethane provided in this embodiment is basically the same as that in Example 1, except that in step S2, a 0.1 g / mL aqueous solution of 3-sulfonyl propyl methacrylate potassium salt is used instead of a 2-acrylamido-2-methylpropanesulfonate sodium aqueous solution, and other conditions are the same, and an antibacterial coating is prepared on the surface of the medical polyurethane.

[0093] Example 5

[0094] The method for preparing an antibacterial coating on medical polyurethane provided in this embodiment is basically the same as that in Example 1, except that in step S2, the concentration of the aqueous solution of sodium 2-acrylamido-2-methylpropane sulfonate is 0.5 g / mL, and other conditions are the same, and an antibacterial coating is prepared on the surface of the medical polyurethane.

[0095] Example 6

[0096] The method for preparing an antibacterial coating on medical polyurethane provided in this embodiment is basically the same as that in Example 1, except that, in step S3, an aqueous hydrochloric acid solution including 0.01 g / mL of cross-linked polylysine (the concentration of HCl is 0.01 g / mL) is replaced by an aqueous hydrochloric acid solution including 0.01 g / mL of cross-linked chitosan (the concentration of HCl is 0.01 g / mL), and other conditions are the same, and an antibacterial coating is prepared on the surface of the medical polyurethane.

[0097] Example 7

[0098] The method for preparing an antibacterial coating on medical polyurethane provided in this embodiment is basically the same as that in Example 1, except that, in step S3, an aqueous hydrochloric acid solution including 0.01 g / mL of polytannic acid (the concentration of HCl is 0.01 g / mL) is used instead of an aqueous hydrochloric acid solution including 0.01 g / mL of cross-linked polylysine (the concentration of HCl is 0.01 g / mL), and other conditions are the same, and an antibacterial coating is prepared on the surface of the medical polyurethane.

[0099] Example 8

[0100] This example is used to illustrate a method for preparing an antibacterial coating on medical organosilicon, in which an anionic polyelectrolyte brush is grafted onto the surface of medical organosilicon by surface-initiated atom transfer radical polymerization, specifically comprising:

[0101] S1. After ultrasonic cleaning of medical organosilicon with deionized water for 5 minutes, take it out and place it in a clean room for drying for 24 hours for use; then treat the medical organosilicon in oxygen plasma for 3 minutes to generate hydroxyl groups on the surface of the medical organosilicon, and then completely immerse the medical organosilicon in a triethylamine ethyl acetate solution with a concentration of 0.1g / mL, stir it in an ice salt bath for 20 minutes, and then heat it at 0.5mL / cm2 A 1 vol% α-bromoisobutyryl bromide ethyl acetate solution was added dropwise, and the mixture was reacted in an ice-salt bath for 2 h. The mixture was taken out and washed with deionized water and ethanol in turn to obtain activated medical organosilicon.

[0102] S2. Put activated medical silicone, 2,2′-bipyridine and cuprous chloride into a Kjeldahl flask, evacuate and pass nitrogen, then add ethyl acetate to completely immerse the activated medical silicone, and the concentration of 2,2′-bipyridine in the solution is 2 mmol / L, and the concentration of cuprous chloride is 0.6 mmol / L; then add 3-sulfonyl methacrylate potassium salt at a final concentration of 1 mmol / L, seal the Kjeldahl flask and react at 50°C for 5 hours, so that the grafting polymerization reaction of 3-sulfonyl methacrylate potassium salt occurs on the surface of the medical silicone to form anionic polyelectrolyte brushes, and then use deionized water and ethanol for ultrasonic cleaning and drying in turn to obtain medical silicone grafted with anionic polyelectrolyte brushes.

[0103] S3. Completely immerse the medical silicone grafted with anionic polyelectrolyte brushes in a hydrochloric acid aqueous solution (HCl concentration is 0.01 g / mL) including 0.01 g / mL of cross-linked chitosan for 20 min, take out and wash with deionized water, and dry to fix the cross-linked chitosan nanoparticles on the anionic polyelectrolyte brushes to obtain an antibacterial coating grafted on the medical silicone.

[0104] Comparative Example 1

[0105] The comparative example provides a method for preparing an antibacterial coating on medical polyurethane, which specifically comprises: S1, ultrasonically cleaning the medical polyurethane with deionized water for 3 minutes, taking it out and drying it in a clean room for 24 hours for use. S2, completely immersing the medical polyurethane in a hydrochloric acid aqueous solution (the concentration of HCl is 0.01 g / mL) containing 0.01 g / mL polylysine for 30 minutes, taking it out and cleaning it with deionized water and drying it to form an antibacterial coating on the surface of the medical polyurethane.

[0106] Comparative Example 2

[0107] The comparative example provides a method for preparing an antibacterial coating on medical organosilicon, which specifically comprises: S1, ultrasonically cleaning the medical organosilicon with deionized water for 5 minutes, taking it out and drying it in a clean room for 24 hours. S2, completely immersing the medical organosilicon in a hydrochloric acid aqueous solution (the concentration of HCl is 0.01 g / mL) containing 0.01 g / mL cross-linked chitosan for 20 minutes, taking it out and cleaning it with deionized water and drying it to form an antibacterial coating on the surface of the medical organosilicon.

[0108] Test Case

[0109] This test example is used to illustrate the relevant properties of the antibacterial coating provided in the above embodiments and comparative examples, and untreated medical polyurethane and medical silicone are used as blank controls. The test specifically includes:

[0110] (1) Hemolysis rate: The hemolysis rate of the antibacterial coating was tested using the method provided in YY / T 1651.1-2019. The test results are shown in Table 1.

[0111] (2) Antibacterial rate: Take 0.05 mL of Staphylococcus aureus at a concentration of 5 × 10 5 The LB medium with 10 cells / mL was evenly coated on the antibacterial coating provided in the above embodiments and comparative examples and the untreated medical polyurethane and medical silicone, and cultured at 37°C (culture conditions) for 24 hours; the bacterial morphology changes on the surface of the antibacterial coating were photographed using a scanning electron microscope, and the number of bacteria on the sample surface was determined by ultrasonic treatment-dilution-plate culture. The antibacterial rate (%) was calculated according to the following formula. The test results are shown in Figure 2. Figures 1 to 4 And as shown in Table 1.

[0112] Antibacterial rate = number of colonies in the sample group / number of colonies in the control group × 100%

[0113] (3) Storage stability: The antibacterial coatings provided in the above examples and comparative examples were placed at room temperature for 7 days, 30 days, and 360 days, respectively, and then taken out and tested according to the test method described in “(2) Antibacterial rate” to obtain the corresponding antibacterial rate;

[0114] (4) pH stimulus responsiveness: The surface of the antibacterial coating provided in Example 1 was coated with bacteria according to the method provided in “(2) Antibacterial rate”, cultured at 37° C. (culture conditions) for 24 h, and stained with a cell viability detection kit (Invitrogen TM L13152) and dyed according to the instructions, and photographed the bacteria on the surface of the antibacterial coating using a scanning electron microscope. The results are as follows Figure 5 Then the antibacterial coating was immersed in 0.01 g / mL NaOH solution for 30 min and the bacteria on the surface of the antibacterial coating were observed. Figure 6 The antibacterial coating was then placed in a 0.01 g / mL cross-linked polylysine hydrochloric acid aqueous solution (HCl concentration 0.01 g / mL) for 30 min, and the surface of the antibacterial coating provided in Example 1 was coated with bacteria according to the method provided in "(2) Antibacterial Rate". After culturing at 37° C. (culture conditions) for 24 h, the bacteria on the surface of the antibacterial coating were observed. The test results are shown in FIG. Figure 7 shown.

[0115] Table 1.

[0116]

[0117] Depend on Figures 1 to 4 As shown in the test results in Table 1, compared with the untreated medical polyurethane and medical silicone and the antibacterial coating provided by the comparative example, the antibacterial coating constructed by Examples 1 to 8 of the present invention has a curled spatial structure under non-strong alkaline conditions, and the anionic polyelectrolyte brushes and the protonated organic nanoparticles are stably combined, giving the antibacterial coating excellent stability and excellent selective killing ability for bacteria.

[0118] Depend on Figures 5 to 7 From the test results shown, it can be seen that the antibacterial coating constructed by the present invention has excellent pH stimulus responsiveness. Under strong alkaline conditions, the anionic polyelectrolyte brush structure thereon stretches, and the anionic polyelectrolyte brush and the protonated organic nanoparticles dissociate to release the dead bacteria and organic nanoparticles on the antibacterial coating, thereby achieving the cleaning of the antibacterial coating. The cleaned antibacterial coating can also recombine with the protonated organic nanoparticles to restore the antibacterial activity and achieve reuse.

[0119] Although the embodiments of the present invention have been shown and described above, it is to be understood that the above embodiments are exemplary and are not to be construed as limitations on the present invention. A person skilled in the art may change, modify, replace and modify the above embodiments within the scope of the present invention without departing from the principles and intent of the present invention.

Claims

1. An antibacterial coating, characterized in that: The antibacterial coating comprises anionic polyelectrolyte brushes and protonated organic nanoparticles, wherein the anionic polyelectrolyte brushes are connected to a substrate material through chemical bonds, and the protonated organic nanoparticles are connected to the anionic polyelectrolyte brushes.

2. The antibacterial coating according to claim 1, characterized in that: The anionic polyelectrolyte brush is obtained by surface grafting polymerization of unsaturated sulfonate on a substrate material; Optionally, the unsaturated sulfonate is selected from one or more of sodium 2-acrylamido-2-methylpropanesulfonate, sodium styrenesulfonate, sodium 2-methyl-2-propylene-1-sulfonate, sodium vinylsulfonate, sodium 3-allyloxy-2-hydroxy-1-propanesulfonate and potassium salt of 3-sulfonyl methacrylate; Optionally, the surface grafting polymerization method is selected from one or more of UV grafting, surface initiated atom transfer radical polymerization, reversible addition-fragmentation chain transfer radical polymerization, ozone grafting and plasma polymerization.

3. The antibacterial coating according to claim 1, characterized in that The protonated organic nanoparticles are obtained by protonating the organic nanoparticles with a strong acid solution; Optionally, the strong acid solution is selected from one or more of a dilute sulfuric acid solution, a dilute hydrochloric acid solution and a dilute nitric acid solution; Optionally, the organic nanoparticles are selected from one or more of cross-linked polyethyleneimine nanoparticles, cross-linked polylysine nanoparticles, cross-linked chitosan nanoparticles, polytannic acid nanoparticles, polypeptide nanoparticles, peptoid nanoparticles and starch nanoparticles.

4. The antibacterial coating according to claim 1, characterized in that The substrate material is a metal material and / or an organic polymer material; Optionally, the metal material is selected from one or more of stainless steel, cobalt alloy, titanium alloy and magnesium alloy; Optionally, the organic polymer material is selected from one or more of polyurethane, polyester fiber, polyvinyl pyrrolidone, polyetheretherketone, polymethyl methacrylate, polyvinyl alcohol, polylactic acid, polyethylene and silicone; Optionally, the base material is polyurethane and / or silicone.

5. The method for preparing the antibacterial coating according to any one of claims 1 to 4, characterized in that: The preparation method comprises: S1, taking the base material and performing activation treatment to generate olefin reaction active sites to obtain an activated base material; S2, taking unsaturated sulfonate and activated base material to carry out surface graft polymerization to obtain a base material grafted with anionic polyelectrolyte brush; S3, using the protonated organic nanoparticles to treat the base material grafted with the anionic polyelectrolyte brush to obtain an antibacterial coating connected to the base material through chemical bonds.

6. The method for preparing the antibacterial coating according to claim 5, characterized in that: The base material is polyurethane.

7. The method for preparing the antibacterial coating according to claim 6, characterized in that: In step S1, the activation treatment specifically includes: taking an ultraviolet light initiator to soak the polyurethane to obtain an activated polyurethane; Optionally, the ultraviolet light initiator is selected from one or more of benzophenone, 4-methylbenzophenone and 2,4,6-trimethylbenzophenone; Optionally, the concentration of the ultraviolet light initiator in the immersion treatment is 0.1 to 10 wt %; Optionally, the soaking treatment time is 5 to 30 minutes; Optionally, in step S2, the surface graft polymerization specifically comprises: applying the unsaturated sulfonate to the surface of the activated substrate material, and subjecting the surface to ultraviolet irradiation treatment to obtain a polyurethane grafted with anionic polyelectrolyte brushes; Optionally, the amount of unsaturated sulfonate applied in the surface graft polymerization is 0.1 to 0.5 g / cm 2 ; Optionally, the ultraviolet radiation has an irradiation wavelength of 200 to 400 nm, an irradiation power of 60 to 120 W, and an irradiation time of 1 to 10 min.

8. The method for preparing the antibacterial coating according to claim 5, characterized in that: The base material is silicone; Optionally, in step S1, the activation treatment specifically comprises: in an inert gas, using plasma to perform surface hydroxylation treatment on the organosilicon to obtain hydroxylated organosilicon; using a halogenating agent to perform a halogenation reaction on the hydroxylated organosilicon to obtain the activated organosilicon; Optionally, the hydroxylation treatment time is 1 to 10 minutes; Optionally, the halogenating agent is α-bromoisobutyryl bromide and / or α-bromoisobutyryl chloride; Optionally, the halogenating agent is added at a concentration of 0.01 to 1 mmol / L; Optionally, the halogenation reaction temperature is 0 to 4°C and the time is 0.5 to 5h; Optionally, in step S2, the surface graft polymerization specifically comprises: in the presence of a cuprous salt and a complexing agent, taking the activated organosilicon and an unsaturated sulfonate for addition polymerization to obtain organosilicon grafted with anionic polyelectrolyte brushes; Optionally, the cuprous salt is cuprous chloride, and the complexing agent is 2,2′-bipyridine; Optionally, the concentration of the unsaturated sulfonate added in the surface graft polymerization is 0.01 to 4 mmol / L, the concentration of the cuprous salt added is 0.01 to 2 mmol / L, and the concentration of the complexing agent added is 0.01 to 2 mmol / L; Optionally, the temperature of the addition polymerization reaction is 40 to 60° C., and the time is 1 to 20 minutes.

9. Use of the antibacterial coating according to any one of claims 1 to 4 in the preparation of antibacterial functional materials.

10. A medical device, characterized in that: The medical device comprises the antibacterial coating according to any one of claims 1 to 4.

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