Method for preparing anti-fouling and sterilizing dual-functional coating on surface of polymer substrate

Abstract

The invention discloses a method for preparing an anti-fouling and sterilizing dual-function coating on the surface of a polymer substrate, which comprises the following steps: activating the surface of the polymer substrate through oxygen plasma to generate free radical sites, soaking the activated substrate in an aqueous solution containing a vinyl anti-fouling monomer, a vinyl quaternary ammonium salt monomer and a thermal initiator, heating to initiate monomer graft copolymerization, and finally forming an anti-fouling and sterilizing dual-function coating on the surface of the base material; according to the preparation method, plasma treatment is used for replacing a traditional tedious site preparation step, the coating preparation process is remarkably simplified, and the preparation time is shortened; the prepared coating can effectively reduce the adhesion amount and survival rate of protein and bacteria on the surface of a base material, can be widely applied to implantable medical devices made of polymer materials such as PU and PVC, and provides a reliable technical scheme for prevention of medical related infections. The method is simple in process, controllable in cost, high in practicability and good in industrialization prospect.

Description

Technical Field

[0001] This invention belongs to the field of medical device surface modification technology, specifically relating to a method for preparing a dual-functional coating for anti-fouling and antibacterial purposes on the surface of a polymer substrate. Background Technology

[0002] Polyurethane (PU), polyvinyl chloride (PVC), and polydimethylsiloxane (PDMS) are common substrates for implantable medical devices such as catheters and artificial organs due to their excellent biocompatibility, mechanical properties, and processing performance. However, these polymer substrates are prone to protein adsorption and bacterial attachment and proliferation, forming biofilms and leading to healthcare-associated infections (CATIs). CATIs not only increase patient suffering and treatment burden but can also lead to serious complications and even endanger life, while also increasing medical costs and causing significant economic losses. To address these issues, various surface modification technologies for medical devices have been developed, among which the preparation of antifouling-bacterial dual-functional coatings on substrate surfaces is one of the most effective methods. Compared to single antifouling or bactericidal coatings, antifouling-bacterial dual-functional coatings can prevent initial protein and bacterial attachment through antifouling components while simultaneously killing existing bacteria through bactericidal components. The synergistic effect of these two components provides more comprehensive and long-lasting prevention of biofilm formation and CATIs.

[0003] Currently, there are two main methods for preparing antifouling-bacterial dual-functional coatings: one is the surface grafting method, which requires generating grafting sites on the surface of a polymer substrate through wet chemical methods such as coating, impregnation, grafting, and deposition, and then using chemical reactions such as esterification to graft the antifouling-bacterial functional components onto the substrate surface. For example, Chinese invention patent application number CN202510624201.7 first deposits a silica substrate on the substrate surface through plasma-enhanced chemical vapor deposition, and then uses a silane coupling reaction to prepare an antifouling-bacterial dual-functional coating. The second is the surface-initiated atom transfer radical polymerization method, which also requires generating initiation sites on the substrate surface through complex processes such as coating and impregnation, and then using the initiation sites to initiate surface free radical polymerization of antifouling monomers and bactericidal monomers to form a functional coating. For example, Chinese invention patents application numbers CN202310687384.8 and CN201810871927.0 both adopt this technical route.

[0004] The two existing methods mentioned above share a common drawback: both require pre-treatment with cumbersome wet chemicals to prepare graftable / initiating sites on the substrate surface. These steps are not only complex and time-consuming, but may also introduce additional chemical residues, affecting the biocompatibility and safety of the coating. Furthermore, the complex process increases the difficulty of cost control and the risk of quality instability during production, hindering industrial applications. Therefore, there is a need to develop a simple, efficient, rapid, and cost-effective method for preparing a dual-functional antifouling and antibacterial coating for polymer substrates to address these issues. Summary of the Invention

[0005] To address the shortcomings of existing technologies in preparing antifouling-bacterial dual-functional coatings, which involve cumbersome and time-consuming steps, this invention provides a method for preparing such coatings on polymer substrates. This method utilizes plasma activation technology to replace traditional complex site preparation processes, shortening the coating preparation cycle and reducing production difficulty. The dual-functional coating, formed by the graft copolymerization of antifouling and bactericidal monomers, effectively inhibits protein adsorption and bacterial adhesion and proliferation, providing reliable anti-infection protection for implantable medical devices.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows: A method for preparing a dual-functional anti-fouling and antibacterial coating on a polymer substrate surface includes the following steps: Step 1, prepare monomer aqueous solution: It is prepared by mixing vinyl antifouling monomer, vinyl quaternary ammonium salt monomer and thermal initiator in deionized water, wherein the total content of monomer is 0.1-10 mol%, the molar ratio of quaternary ammonium salt monomer to antifouling monomer is 5-80%, and the molar ratio of thermal initiator to monomer is 1-5%; Step 2, Plasma activation of substrate surface: Oxygen is used as the plasma gas. The surface of the polymer substrate is activated through a vacuum plasma chamber or a plasma spray gun. The oxygen flow rate is 10-200 scams, the plasma power is 50-200W, and the activation time is 1-20min, so that free radical sites are generated on the substrate surface. Step 3, graft copolymerization reaction: Immerse the activated substrate in the monomer aqueous solution prepared in step 1, and keep it at 50-90℃ for 20-90 min to allow the monomer to graft copolymerize on the substrate surface. Step 4, Cleaning treatment: Use deionized water to thoroughly clean the substrate surface to remove excess homopolymer and obtain a dual-function coating that is both anti-fouling and antibacterial.

[0007] In a preferred embodiment of the present invention, the vinyl antifouling monomer in step 1 is one or a combination of polyethylene glycol diacrylate, vinylpyrrolidone CAS88-12-0, methacryloylethyl sulfobetaine CAS3637-26-1, methacrylic acid carboxybetaine CAS24249-95-4 and 2-methacryloyloxyethyl phosphorylcholine.

[0008] In a preferred embodiment of the present invention, the vinyl quaternary ammonium salt monomer in step 1 is one or a combination of methacrylamide propyltrimethylammonium chloride, trimethylammonium chloride, acryloyloxyethyltrimethylammonium chloride, methacryloxyethyltrimethylammonium chloride, benzylethyltrimethylammonium chloride, and dimethyl diallyl ammonium chloride.

[0009] In a preferred embodiment of the present invention, the thermal initiator in step 1 is one of potassium persulfate, sodium persulfate, and ammonium persulfate.

[0010] In a preferred embodiment of the present invention, the polymer substrate in step 2 is one of PU, PVC, PDMS, PTFE, PET, PP, and PVDF.

[0011] The present invention also provides a dual-function coating for anti-fouling and antibacterial preparation on the surface of a polymer substrate prepared by the above method. The coating has an adhesion inhibition rate of ≥99% for proteins and an adhesion inhibition rate of ≥99% for Escherichia coli, and can reduce the survival rate of Escherichia coli to below 15%.

[0012] The present invention also provides an application of the above-mentioned polymer substrate surface preparation of an anti-fouling and antibacterial dual-function coating in implantable medical devices.

[0013] Compared with the prior art, the present invention has the following beneficial effects: (1) Simplify the preparation process and shorten the production cycle: The present invention uses oxygen plasma activation technology to generate free radical sites on the substrate surface, which replaces the cumbersome wet chemical treatment steps such as coating, impregnation and deposition in the traditional method, shortens the total coating preparation time, greatly improves production efficiency and reduces process complexity.

[0014] (2) Excellent coating performance and synergistic dual-function effect: This invention achieves both antifouling and bactericidal functions through graft copolymerization of antifouling monomers and quaternary ammonium salt bactericidal monomers. Experiments have shown that the coating inhibits the adhesion of BSA (bovine serum albumin) by more than 99% and also inhibits the adhesion of Escherichia coli by ≥99%, and can reduce the survival rate of Escherichia coli to below 15%, effectively preventing protein adsorption and bacterial proliferation, and preventing biofilm formation and medical-related infections.

[0015] (3) The process is environmentally friendly and safe, and has good biocompatibility: The preparation process of this invention uses water as a solvent, which avoids the use of organic solvents and reduces the risk of environmental pollution and reagent residues; the monomers and initiators selected have good biocompatibility, and after cleaning with deionized water, there are no excess impurities on the coating surface, which meets the biosafety requirements of medical devices.

[0016] (4) Wide range of applicable substrates and good industrialization prospects: The method of the present invention is applicable to a variety of commonly used medical device polymer substrates such as PU, PVC, and PDMS. There is no need to adjust the core process for different substrates, and it has strong versatility. Moreover, the process steps are simple, the equipment requirements are moderate, the cost is controllable, and it is easy to achieve large-scale production, which has broad prospects for industrial application. Attached Figure Description

[0017] To more clearly illustrate the technical solutions in the embodiments or prior art, the drawings used in the description of the embodiments or prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0018] Figure 1 This invention provides a flowchart of a method for preparing a dual-functional anti-fouling and antibacterial coating on the surface of a polymer substrate.

[0019] Figure 2 This is a schematic diagram of the microstructure of a dual-functional anti-fouling and antibacterial coating prepared on the surface of a polymer substrate, as provided in an embodiment of the present invention. Detailed Implementation

[0020] The technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of this application, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this application without creative effort are within the scope of protection of this application.

[0021] like Figure 1 As shown, this embodiment of the invention provides a method for preparing a dual-functional anti-fouling and antibacterial coating on the surface of a polymer substrate, comprising the following steps: Step 1, prepare monomer aqueous solution: It is prepared by mixing vinyl antifouling monomer, vinyl quaternary ammonium salt monomer and thermal initiator in deionized water, wherein the total content of monomer is 0.1-10 mol%, the molar ratio of quaternary ammonium salt monomer to antifouling monomer is 5-80%, and the molar ratio of thermal initiator to monomer is 1-5%.

[0022] Step 2, Plasma activation of substrate surface: Oxygen is used as the plasma gas. The surface of the polymer substrate is activated through a vacuum plasma chamber or plasma spray gun. The oxygen flow rate is 10-200 scams, the plasma power is 50-200W, and the activation time is 1-20min. This generates free radical sites on the substrate surface, providing active centers for the subsequent graft copolymerization reaction.

[0023] Step 3, Graft copolymerization reaction: The activated substrate is immersed in the monomer aqueous solution prepared in Step 1 and kept at 50-90℃ for 20-90 min to allow the monomer to graft copolymerize on the substrate surface. Under the synergistic effect of the thermal initiator and the free radical sites on the substrate surface, the vinyl antifouling monomer and the vinyl quaternary ammonium salt monomer undergo a graft copolymerization reaction on the substrate surface to form a uniform functional coating.

[0024] Step 4, Cleaning treatment: After the reaction is completed, take out the substrate and use deionized water to thoroughly clean the surface of the substrate to remove monomers and homopolymers that did not participate in the grafting reaction, and obtain a dual-function coating that is both anti-fouling and antibacterial.

[0025] The vinyl antifouling monomers mentioned in step 1 are one or more combinations of polyethylene glycol diacrylate, vinylpyrrolidone (CAS88-12-0), methacryloylethyl sulfobetaine (CAS3637-26-1), carboxymethyl betaine (CAS24249-95-4), and 2-methacryloyloxyethyl phosphorylcholine. These monomers have good hydrophilicity and anti-bioadhesion properties, effectively preventing the initial adhesion of proteins and bacteria to the coating surface.

[0026] The vinyl quaternary ammonium salt monomer mentioned in step 1 is one or a combination of methacrylamide propyltrimethylammonium chloride, trimethylammonium chloride, acryloyloxyethyltrimethylammonium chloride, methacryloxyethyltrimethylammonium chloride, benzylethyltrimethylammonium chloride, and dimethyldiallylammonium chloride. The quaternary ammonium salt group has a strong bactericidal effect, can disrupt bacterial cell membrane structure, inhibit bacterial proliferation, and has low biotoxicity, making it suitable for surface modification of medical devices.

[0027] The thermal initiator mentioned in step 1 is one of potassium persulfate, sodium persulfate, or ammonium persulfate. These initiators decompose under heating conditions to generate free radicals, initiating monomer polymerization reactions. They also exhibit good solubility in aqueous solutions, mild reaction characteristics, and low residual toxicity.

[0028] The polymer substrate mentioned in step 2 is one of PU, PVC, PDMS, PTFE, PET, PP, and PVDF. These are all commonly used polymer materials for implantable medical devices, and the method of the present invention is well-suited for them.

[0029] The present invention also provides a dual-function coating for anti-fouling and antibacterial preparation on the surface of a polymer substrate prepared by the above method. The coating has an adhesion inhibition rate of ≥99% for proteins and an adhesion inhibition rate of ≥99% for Escherichia coli, and can reduce the survival rate of Escherichia coli to below 15%. Figure 2 This is the microstructure of a prepared antifouling and antibacterial coating.

[0030] The present invention also provides an application of the above-mentioned polymer substrate surface preparation of an anti-fouling and antibacterial dual-function coating in implantable medical devices.

[0031] The technical principle of this invention is as follows: Plasma is a quasi-neutral gas composed of particles such as electrons, ions, and free radicals, and possesses high reactivity. When oxygen plasma is used to activate the surface of a polymer substrate, high-energy particles collide with the molecules on the substrate surface, breaking the chemical bonds between molecular chains and generating a large number of free radical sites on the surface. Simultaneously, the introduction of oxygen can also introduce polar groups such as hydroxyl and carboxyl groups onto the substrate surface, further enhancing surface reactivity. Subsequently, the activated substrate is immersed in an aqueous solution containing antifouling monomers, bactericidal monomers, and a thermal initiator. Under heating conditions, the thermal initiator decomposes to generate free radicals, which interact with the free radical sites on the substrate surface to initiate a graft copolymerization reaction between the two monomers. The antifouling monomer imparts good hydrophilicity and anti-bioadhesion capabilities to the coating, while the bactericidal monomer imparts strong antibacterial and bactericidal properties. The coating formed through the copolymerization reaction possesses both antifouling and bactericidal functions and is chemically bonded to the substrate, exhibiting strong adhesion and good stability.

[0032] The technical solution of the present invention will be described in detail below with reference to specific embodiments, but the scope of protection of the present invention is not limited to the following embodiments.

[0033] Example 1 describes a scheme for preparing a dual-functional anti-fouling and antibacterial coating using PDMS (polydimethylsiloxane) as the substrate. The specific steps are as follows: Step 1: Prepare an aqueous monomer solution using methacryloylethyl sulfobetaine, methacryloyloxyethyl trimethylammonium chloride, and potassium persulfate. Methacrylethyl sulfobetaine is the antifouling monomer, methacryloyloxyethyl trimethylammonium chloride is the quaternary ammonium salt monomer, and potassium persulfate is the initiator. The total monomer content in the aqueous solution is 2 mol%, the molar ratio of the quaternary ammonium salt monomer to the antifouling monomer is 20%, and the molar ratio of the initiator to the total monomer content is 5%. Step 2: Activate the PDMS surface using oxygen plasma at an oxygen flow rate of 25 scams, a plasma power of 50 W, and an activation time of 10 min to generate free radical sites on the PDMS surface. Step 3: Immerse the activated PDMS substrate in the aqueous monomer solution, then heat the aqueous solution to 60°C and maintain the temperature for 30 min to induce a graft copolymerization reaction of the monomers on the PDMS surface. Step 4: After the reaction is complete, remove the PDMS substrate, rinse the surface repeatedly with deionized water to remove ungrafted monomers and homopolymers, and air dry to obtain a dual-function anti-fouling and antibacterial coating.

[0034] Results: The anti-protein adhesion ability of the coating was tested using a 1 mg / mL BSA solution. Compared with the PDMS substrate itself, the anti-fouling and antibacterial coating reduced the amount of BSA adhesion by 99%. The antibacterial adhesion ability and antibacterial ability of the coating were tested using E. coli. Compared with the PDMS substrate itself, the anti-fouling and antibacterial coating reduced the amount of E. coli adhesion by 99%, and the survival rate decreased from 100% to 15%.

[0035] Example 2 describes a scheme for preparing a dual-functional anti-fouling and antibacterial coating using PVC (polyvinyl chloride) as the substrate. The specific steps are as follows: Step 1: Prepare an aqueous monomer solution using vinylpyrrolidone, benzylethyltrimethylammonium chloride, and ammonium persulfate. Vinylpyrrolidone is the antifouling monomer, benzylethyltrimethylammonium chloride is the quaternary ammonium salt monomer, and ammonium persulfate is the initiator. The total monomer content in the aqueous solution is 3 mol%, the molar ratio of the quaternary ammonium salt monomer to the antifouling monomer is 50%, and the molar ratio of the initiator to the total monomer content is 1%. Step 2: Activate the PVC substrate surface using oxygen plasma at an oxygen flow rate of 50 scams, a plasma power of 100 W, and an activation time of 7 minutes to generate free radical sites on the PVC surface. Step 3: Immerse the activated PVC substrate in the aqueous monomer solution, then heat the solution to 60°C and maintain the temperature for 30 minutes to complete the graft copolymerization reaction. Step 4: Thoroughly rinse the PVC substrate surface with deionized water to remove excess homopolymer. After drying, obtain an antifouling-antibacterial dual-functional coating.

[0036] Results: The coating's resistance to protein adhesion was tested using a 1 mg / mL BSA solution. Compared to the PVC substrate itself, the antifouling and antibacterial coating reduced BSA adhesion by 99%. The coating's resistance to bacterial adhesion and antibacterial activity was tested using E. coli. Compared to the PDMS substrate itself, the antifouling and antibacterial coating reduced E. coli adhesion by 99%, and the survival rate decreased from 100% to 15%.

[0037] Alternative embodiment 1: Replace the oxygen plasma with plasma of other gases, such as argon or helium.

[0038] In the alternative embodiment 2, the thermal initiation in preparation step 3 is replaced with photoinitiation, and the initiator is replaced with a corresponding photoinitiator.

[0039] This invention utilizes plasma graft copolymerization to prepare an antifouling and antibacterial coating on a polymer substrate surface. First, the polymer substrate surface is activated with plasma, generating free radical sites. Then, vinyl antifouling monomers and vinyl quaternary ammonium salt monomers undergo free radical polymerization on the activated substrate surface. Due to the presence of free radical sites, the monomers also undergo graft copolymerization on the substrate surface during free radical polymerization, thereby forming a dual-functional antifouling and antibacterial coating. The method proposed in this invention uses simple plasma treatment to replace cumbersome coating, impregnation, grafting, and deposition methods, thereby generating graftable / initiating sites on the polymer substrate surface. Therefore, compared to existing technologies, this invention simplifies the method for preparing a dual-functional antifouling and antibacterial coating on a polymer substrate surface.

[0040] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely preferred examples and are not intended to limit the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the present invention as claimed. The scope of protection of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for preparing a dual-functional anti-fouling and antibacterial coating on the surface of a polymer substrate, characterized in that, Includes the following steps: Step 1, prepare monomer aqueous solution: It is prepared by mixing vinyl antifouling monomer, vinyl quaternary ammonium salt monomer and thermal initiator in deionized water, wherein the total content of monomer is 0.1-10 mol%, the molar ratio of quaternary ammonium salt monomer to antifouling monomer is 5-80%, and the molar ratio of thermal initiator to monomer is 1-5%; Step 2, Plasma activation of substrate surface: Oxygen is used as the plasma gas. The surface of the polymer substrate is activated through a vacuum plasma chamber or a plasma spray gun. The oxygen flow rate is 10-200 scams, the plasma power is 50-200W, and the activation time is 1-20min, so that free radical sites are generated on the substrate surface. Step 3, graft copolymerization reaction: Immerse the activated substrate in the monomer aqueous solution prepared in step 1, and keep it at 50-90℃ for 20-90 min to allow the monomer to graft copolymerize on the substrate surface. Step 4, Cleaning treatment: Use deionized water to thoroughly clean the substrate surface to remove excess homopolymer and obtain a dual-function coating that is both anti-fouling and antibacterial.

2. The method for preparing an anti-fouling and antibacterial dual-functional coating on the surface of a polymer substrate according to claim 1, characterized in that, The vinyl antifouling monomer mentioned in step 1 is one or a combination of polyethylene glycol diacrylate, vinylpyrrolidone (CAS88-12-0), methacryloyl ethyl sulfobetaine (CAS3637-26-1), carboxymethyl methacrylate betaine (CAS24249-95-4), and 2-methacryloyloxyethyl phosphorylcholine.

3. The method for preparing an anti-fouling and antibacterial dual-functional coating on the surface of a polymer substrate according to claim 1, characterized in that, The vinyl quaternary ammonium salt monomer mentioned in step 1 is one or a combination of methacrylamide propyltrimethylammonium chloride, trimethylammonium chloride, acryloyloxyethyltrimethylammonium chloride, methacryloxyethyltrimethylammonium chloride, benzylethyltrimethylammonium chloride, and dimethyl diallyl ammonium chloride.

4. The method for preparing an anti-fouling and antibacterial dual-functional coating on the surface of a polymer substrate according to claim 1, characterized in that, The thermal initiator mentioned in step 1 is one of potassium persulfate, sodium persulfate, or ammonium persulfate.

5. The method for preparing an anti-fouling and antibacterial dual-functional coating on the surface of a polymer substrate according to claim 1, characterized in that, The polymer substrate mentioned in step 2 is one of PU, PVC, PDMS, PTFE, PET, PP, and PVDF.

6. A dual-functional anti-fouling and antibacterial coating is prepared on the surface of the polymer substrate obtained by the method according to any one of claims 1-5, characterized in that... The coating has an adhesion inhibition rate of ≥99% for proteins and ≥99% for Escherichia coli, and can reduce the survival rate of Escherichia coli to below 15%.

7. The application of the anti-fouling and antibacterial dual-function coating prepared on the surface of the polymer substrate as described in claim 6 in implantable medical devices.

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