Dual-sterilization and anti-sticking composite cross-linked coating as well as preparation method and application thereof

Abstract

The invention discloses a double-sterilization-anti-sticking composite cross-linked coating as well as a preparation method and application thereof, and belongs to the technical field of functional polymer materials. The coating comprises the following raw materials in parts by weight: 5-30 parts of a cross-linkable release type multifunctional branched polymer and 30-95 parts of a cross-linkable functional polymer. According to the double-sterilization-anti-adhesion composite cross-linked coating, the advantages of contact sterilization, antibacterial factor release and adhesion resistance can be combined together, on one hand, the super-hydrophilic component can effectively prevent initial adhesion of bacteria and protein, and even if a small amount of bacteria fall into the surface of the coating, the contact sterilization component can effectively kill a small amount of adhesion bacteria; the formation of bacteria and biological membranes is avoided; in addition, the introduction of releasable antibacterial molecules can effectively enhance the antibacterial effect, and the purpose of deeply killing pathogens is achieved.

Description

Technical Field

[0001] The present invention belongs to the technical field of functional polymer materials, and specifically relates to a dual sterilization-anti-adhesion composite cross-linking coating and a preparation method and application thereof. Background Art

[0002] In recent years, the demand for antibacterial coatings in public health, medical equipment, marine industry, textiles and water purification systems has been increasing. Antibacterial coatings are a kind of solid film that can evenly cover and well adhere to the surface of an object. It is a material with protective, decorative or special functions. If classified according to the dispersion state of film-forming substances and pigments, there are solvent-based antibacterial coatings, water-based antibacterial coatings, powder antibacterial coatings, high-energy ray-cured antibacterial coatings, etc. With the development of society, people's daily lives and many fields such as buildings, ships, and circulating cooling water have antibacterial needs. Therefore, antibacterial coatings with improved antibacterial functions are one of the development directions of the coating industry. Antibacterial coatings can be made by adding certain suitable and stable antibacterial materials to the coating. Antibacterial coatings can be directly applied on various materials and have attracted much attention due to their ease of use.

[0003] The most common methods include anti-bacterial adhesion, contact killing, killing by releasing antibacterial factors, and sterilization-release methods (ACS Appl. Mater. Interfaces 2021, 13, 18, 20921–20937). Anti-bacterial adhesion uses the principles of hydration of hydrophilic coatings to resist protein adsorption and initial adhesion of microorganisms, thereby preventing bacteria from forming biofilms on the surface of materials to a certain extent. For example, the invention patent CN 113881086A uses a copolymer of borneol acrylate (BA) and polyethylene glycol diacrylate (PEGDA) to construct an amphiphilic stereochemical polymer coating with antimicrobial adhesion. However, this type of anti-adhesion coating cannot kill bacteria or completely prevent bacterial attachment. A small number of adhered bacteria will slowly accumulate and eventually form a biofilm. The contact killing coating strategy is to kill bacteria or limit the growth of attached bacteria through contact sterilization or blocking key metabolic or reproductive pathways to inhibit the formation of bacterial biofilms. For example, a type of antibacterial material that is currently widely used, cationic polymers, has an antibacterial mechanism that achieves the antibacterial purpose by destroying the cell wall / membrane of microorganisms, but this type of bactericidal material cannot effectively release antibacterial components and has limited bactericidal performance. Releasing antibacterial factors to kill is to compound cationic polymerization with releasable nanoparticles to achieve the purpose of contact and release sterilization. For example, the invention patent CN105999407A uses chitosan, silver nitrate and polyvinyl alcohol as raw materials to prepare an antibacterial composite gel coating. Among them, silver nanoparticles can achieve efficient sterilization through mechanisms such as contact and silver ion release, thereby greatly improving the bactericidal performance. However, the disadvantage of this bactericidal strategy is that the killed bacteria and debris will accumulate on the surface, covering the surface of the coating, thereby resulting in the loss of the surface bactericidal function. The more popular one is the sterilization-release method, which, on the one hand, utilizes the contact antibacterial mechanism of the antibacterial material-cationic polymer to achieve the antibacterial purpose by destroying the cell wall / membrane of microorganisms, and on the other hand, the hydration of the super-hydrophilic coating and other principles resist the adhesion of proteins, bacteria or the bodies of killed bacteria. For example, the invention patent CN112048223A uses responsive monomers and antifouling monomers to prepare antifouling-releasing microgel balls or responsive polymer brushes, and then combines them with catechol polymers, Fe 3+The solution is co-precipitated to obtain an antibacterial surface with multifunctional response of "anti-fouling-bactericidal-release". CN 109232834 A uses responsive monomers and anti-fouling monomers to prepare a responsive polymer brush, which is then grafted with triclosan antibacterial agent or loaded with silver nanoparticles to obtain an antibacterial surface with multifunctional response of "anti-fouling-bactericidal-release". CN110484062B uses dopamine to construct a method of "anti-fouling-bactericidal-release" surface coating, that is, adding the stimulus-responsive polymer containing epoxy group, bactericidal polymer and anti-fouling polymer to the dopamine solution, and co-precipitating on the substrate. Invention patent CN108755145A uses the super-hydrophobicity of vinyl silicone oil to reduce bacterial adhesion, making it easy to remove bacteria attached to the surface of the material, and uses the characteristics of amphiphilic vinyl nitrogen-containing compounds that can act on cell membranes and cause the release of intracellular substances to inhibit bacterial growth, thereby achieving the purpose of inhibiting bacterial adhesion and reproduction. Invention patent CN105646928A uses thermodynamic spontaneous reaction between active ester end groups of N-hydroxysuccinimide and primary amine groups of collagen to prepare materials that can kill bacteria and prevent adhesion of microorganisms such as bacteria. CN108299667B uses polyimidazole salts and anti-protein adhesion structural units to be grafted onto the surface of polymer materials through free radical reaction, and inhibits the normal physiological function of bacterial cell membranes through the action of surface charge, thereby inhibiting the reproduction of bacteria and achieving antibacterial and anti-protein adhesion. CN110330658A mixes responsive monomers with epoxy monomers and then conducts free radical copolymerization, then mixes with epoxy-containing hydrophilic polymers and dissolves them in a solvent, adds amino-containing bactericides to conduct epoxy ring-opening reaction to obtain bactericidal, low bacterial adhesion, and bacterial release antibacterial hydrogels. CN112048224 B uses free radical polymerization to prepare responsive microgel spheres, and then co-deposits the prepared microgel spheres, catechol derivatives and metal bactericides on a substrate to obtain an antibacterial surface with dual functions of bactericidal-release. Although the "bactericidal-release" surface combines the advantages of contact antibacterial and anti-bacterial adhesion, its antibacterial efficiency and long-term antibacterial effect will be affected, thus limiting its scope of use. In addition, when constructing such coatings, chemical grafting methods are generally used, which is a cumbersome process and requires the use of a large amount of organic reagents, which will cause environmental pollution problems. Summary of the invention

[0004] In view of the above-mentioned problems existing in the prior art, the purpose of the present application is to design and provide a technical solution for a dual sterilization-anti-adhesion composite cross-linked coating and its preparation method and use, which can combine the advantages of contact sterilization, release of antibacterial factors and anti-adhesion. On the one hand, the superhydrophilic component can effectively prevent the initial adhesion of bacteria and proteins. Even if a small amount of bacteria falls on the surface of the coating, the contact sterilization component can effectively kill a small amount of adhered bacteria, thereby avoiding the formation of bacteria and biofilms; in addition, the introduction of releasable antibacterial molecules can effectively enhance the antibacterial effect and achieve the purpose of deep-level killing of pathogens, thereby overcoming the shortcomings of the prior art such as unsatisfactory sterilization effect of the antibacterial surface and inability to remove dead bacteria.

[0005] The dual sterilization-anti-adhesion composite cross-linked coating is characterized in that the raw materials of the coating include 5-30 parts of cross-linkable release-type multifunctional branched polymer and 30-95 parts of cross-linkable functional polymer;

[0006] The cross-linkable and releasable multifunctional branched polymer has a three-dimensional multi-active group branched polymer compound as the core, and is modified with reactive functional groups, antibacterial and antiviral functional groups, anti-adhesive functional groups, functional active molecular groups and releasable antibacterial active substances;

[0007] The cross-linkable functional polymer is at least one of oil, oil processing product, cellulose derivative, natural resin, synthetic polyester, synthetic emulsion or its derivatives.

[0008] The dual sterilization-anti-adhesion composite cross-linked coating is characterized in that: the molecular weight of the cross-linkable and releasable multifunctional branched polymer is 800-60000, preferably 20000-30000; the molar ratio of the reactive functional group elements is 5-10%, the molar content of the antibacterial and antiviral functional groups is 30-50%, the molar content of the anti-adhesion functional groups is 20-50%, and the molar content of the functional active molecular groups is 20-50%.

[0009] The dual sterilization-anti-adhesion composite cross-linked coating is characterized in that: the three-dimensional multi-active group branched polymer compound is at least one of a hyperbranched polymer containing multi-active groups, a dendritic polymer containing multi-active groups or their derivatives; preferably at least one of hyperbranched / dendritic polyamide amine, hyperbranched polyethyleneimine, hyperbranched polyamino acid, hyperbranched polypeptide or their derivatives; more preferably at least one of modified hyperbranched / dendritic polyamide amine, modified hyperbranched polyethyleneimine, modified hyperbranched polyamino acid, and modified hyperbranched polypeptide;

[0010] The reactive group is at least one of an amino group, a carboxyl group, a maleimide group, a N-hydroxysuccinimide group, an azide group, an alkynyl group, a thiol group, an aldehyde group, and a hydroxyl group;

[0011] The antibacterial and antiviral functional group is at least one of quaternary ammonium salts, quaternary phosphonium salts, guanidines, halogenated phenols, halamines or their derivatives;

[0012] The anti-stick functional group is at least one of propane sultone, acrylic acid, methacrylic acid, acryloxyphosphocholine, methacryloyloxyphosphocholine, acrylamidophosphocholine, methacryloylphosphocholine, acryloxysulfonic acid betaine, methacryloyloxysulfonic acid betaine, acrylamidosulfonic acid betaine, methacryloylsulfonic acid betaine, acrylamidosulfonic acid betaine, methacryloylsulfonic acid betaine, acryloxycarboxylic acid betaine, acrylamidocarboxylic acid betaine, methacryloylcarboxylic acid betaine, monopolyethylene glycol acrylate, monopolyethylene glycol methacrylate, hydroxyethyl acrylate, hydroxyethyl methacrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate, acrylamide, methacrylamide, vinyl pyrrolidone, styrene sulfonic acid and 2-acrylamide-2-methylpropane sulfonic acid or its derivatives;

[0013] The functionally active molecular group is at least one of collagen, gelatin, fibrin adhesive, cellulose, starch, alginate, chitosan, agarose, hyaluronic acid or its derivatives;

[0014] The releasable antibacterial active substance is at least one of tetracycline broad-spectrum antibiotics, biguanide compounds, aminoglycoside antibiotics, antibacterial polypeptides, nano-inorganic antibacterial agents, metal ions, plant-derived antibacterial agents or their derivatives, preferably at least one of antibacterial polypeptides, nano-inorganic antibacterial agents, metal ions, and plant-derived antibacterial agents.

[0015] The dual sterilization-anti-adhesion composite cross-linked coating is characterized in that the synthetic polyester is selected from at least one of polyvinyl alcohol ester, polybutylene terephthalate, polycarbonate, polyphenylene terephthalate-butylene terephthalate, polylactic acid polyester, and acrylic polymers; preferably, the functional polymer is acrylic polymer, polyurethane, polybutylene succinate, polybutylene terephthalate-adipate, polybutylene succinate-co-terephthalate, polybutylene succinate-adipate-butylene terephthalate, polycaprolactone, polypropylene carbonate, polyhydroxyalkanoic acid, polyhydroxybutyric acid-hexanoate, poly 3,4-hydroxybutyrate, cellulose ester, cellulose ether, cellulose carbamate, cellulose nitrate, cellulose sulfonate, chitosan, hyaluronic acid, alginate, agarose, collagen, silk fibroin, silk protein, gelatin, polyphenols, polypeptides or at least one of their derivatives.

[0016] The method for preparing the dual sterilization-anti-adhesion composite cross-linked coating is characterized by comprising the following steps:

[0017] 1) Using three-dimensional multi-active group branched polymer compounds to prepare cross-linkable multifunctional branched polymers;

[0018] 2) subjecting the cross-linkable multifunctional branched polymer obtained in step 1) to a composite reaction with a releasable antibacterial active substance, and then dialyzing to obtain a cross-linkable releasable multifunctional branched polymer;

[0019] 3) pre-crosslinking the crosslinkable releasable multifunctional branched polymer obtained in step 2) with the crosslinkable functional polymer;

[0020] 4) preparing a functional coating using the pre-crosslinked solution obtained in step 3);

[0021] 5) Post-processing the sample of step 4) to obtain a dual sterilization-anti-adhesion composite cross-linked coating.

[0022] The dual bactericidal-anti-adhesive composite cross-linked coating is characterized in that the specific method in step 1) is: dissolving a three-dimensional multi-active group branched polymer compound in a solvent, wherein the solvent is at least one of water, ethanol, methanol, and acetone, and adding compounds containing antibacterial and antiviral functional groups, compounds containing anti-adhesive functional groups, and functionally active molecular group substances respectively, removing the solvent after the reaction, and obtaining a cross-linkable multifunctional branched polymer.

[0023] The preparation method of the dual sterilization-anti-adhesion composite cross-linked coating is characterized in that in step 2), the mass proportion of the release-type antibacterial active substance is 5-10%; the conditions of the composite reaction are: temperature 20-80°C, reaction time 6-24 hours, dialysis bag molecular weight cutoff 8000-15000, dialysate is one of distilled water and PBS buffer solution, and dialysis time 12-24 hours; preferably, the temperature is 30-70°C, the reaction time is 10-20 hours, the dialysis bag molecular weight cutoff is 10000-12000, and the dialysis time is 15-20 hours;

[0024] The conditions for pre-crosslinking in step 3) are: temperature 60-80° C., reaction time 12-24 hours.

[0025] The method for preparing a dual sterilization-anti-adhesion composite cross-linked coating is characterized in that in step 4): the functional coating is prepared by dip coating, spin coating or spray coating, and the thickness of the functional coating is 500nm-2mm, preferably 10μm-1mm;

[0026] The dipping conditions are: temperature 60-80°C, time 10-30 seconds;

[0027] The spin coating conditions are: temperature 60-80° C., time 30-60 seconds; the spray coating conditions are: temperature 60-80° C., time 20-60 seconds.

[0028] The method for preparing a dual sterilization-anti-stick composite cross-linked coating is characterized in that in step 5): the post-treatment includes natural drying, vacuum drying, and solution phase transformation. The natural drying conditions are: temperature is room temperature, time is 6-24 hours; the vacuum drying conditions are: temperature is 25-60°C, time is 6-12 hours; the solution phase transformation conditions are: temperature is 15-37°C, time is 15-30 minutes.

[0029] The application of the dual sterilization-anti-adhesion composite cross-linked coating in the preparation of antibacterial coatings includes application as antibacterial coatings on the surfaces of various assets and commodities in public places and households.

[0030] Specifically, the antibacterial coating of the present invention can be applied to public places such as medical treatment, schools, locker rooms, restaurants, bank ATM machines, communication equipment and public transportation. The antibacterial coating is applied to the surface protection of ventilation systems, ceilings, pipes, wall metals and various metal facilities in public places, and can inhibit the residue and growth of pathogens in the equipment and facilities in these places;

[0031] Pregnant women, infants, and children are relatively immune-compromised groups, and are also susceptible to bacteria and viruses. The use of antibacterial coatings by pregnant women or families with children can help them avoid harm from bacteria and mold as much as possible. Therefore, the application of antibacterial coatings on household appliances, doors and windows, and steel furniture in the home is of great practical significance.

[0032] Surfaces such as glass, fiberglass, plastic, metal, wood, ceramic, composites and natural materials can be coated with antimicrobial coatings and can be used in air conditioners, furnace air filters, automobiles, air purification devices, aquarium filters, recirculating air handlers, vehicle parts, etc.

[0033] Roofing materials including granules, shakes, heads, felts, underlayments, membranes, tiles and synthetic exterior antimicrobial coatings, building materials including wood composites, wallboard, lumber, siding, stainless steel, cabinets and insulation, ceilings, conveyors, concrete products and other exterior antimicrobial coatings;

[0034] Antimicrobial coatings can be applied to different surfaces such as floor coverings, healthcare facilities, fiberglass duct boards, general purpose containers, non-food contact tops, furniture, bathrooms, mats, plumbing supplies, vacuum cleaners and filters, sheets, foams for cushioning and packaging, and many more.

[0035] The beneficial effects of the present invention are as follows:

[0036] 1) The three-dimensional multi-active group branched polymer compound used has abundant terminal active functional groups, and the terminal reaction sites are controllable. The terminal functional groups can be functionally designed, thereby giving the coating material multifunctional properties and realizing multiple functions and multiple uses of one material.

[0037] 2) The three-dimensional multi-active group branched polymer compound is highly designable, and its molecular particle size increases from a few nanometers to more than ten nanometers. It has a cavity inside and can be used as a carrier of nano-drugs, or encapsulate a specific number of drug molecules, to achieve the purpose of drug loading and controlled release, and achieve the purpose of deep-level killing of pathogenic microorganisms.

[0038] 3) Three-dimensional multi-active group branched polymer compounds can provide more terminal active functional groups, can combine more functional groups, and can form more cross-linking sites with functional polymers, which can achieve stable intra-layer and inter-layer cross-linking between the coating and the substrate, thereby having better long-term stability.

[0039] 4) The formed dual sterilization-anti-adhesion composite cross-linked coating not only utilizes the functional groups of the cross-linkable and releasable multifunctional branched polymer to kill pathogenic microorganisms that fall on the surface of the coating, but also utilizes the strong hydration of the super-hydrophilic component to make it difficult for bacterial corpses and proteins in the body to adhere to its surface, thereby achieving the purpose of anti-adhesion. In addition, the antibacterial active substances loaded in the cavity can also kill pathogenic microorganisms at a deeper level, achieving a longer-lasting, broader-spectrum, and more lasting antibacterial purpose.

[0040] 5) The thickness of the formed dual bactericidal-anti-adhesive composite cross-linked coating is controllable, which can effectively increase the density of the effective antibacterial components of the coating and has mechanical stability.

[0041] 6) The formed dual sterilization-anti-adhesion composite cross-linked coating is applicable to almost any substrate material and has universal applicability. At the same time, it does not cause any damage to the substrate material, protects the structural properties of the substrate material, and is conducive to industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] Figure 1 Schematic diagram of the structure of the cross-linkable, releasable multifunctional branched polymer of the present invention;

[0043] Figure 2 Schematic diagram of the preparation of the dual sterilization-anti-adhesion composite cross-linked coating of the present invention. DETAILED DESCRIPTION

[0044] The present invention is described clearly and completely below in conjunction with the accompanying drawings and specific embodiments. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0045] The experimental test method used in the present invention is as follows:

[0046] (1) Sterilization performance test:

[0047] Escherichia coli (Gram-negative bacteria) and Staphylococcus aureus (Gram-positive bacteria) were used to test the antifouling, bactericidal and regeneration properties of the polymer surface. The two bacteria were first incubated overnight on Luria-Bertani (LB) agar medium at 37°C, and then the bacterial colonies on the plate were inoculated into 40 mL LB medium and shaken at 37°C for 10 hours. The bacterial solution was diluted with pure LB to a dilute bacterial solution with an OD value of 0.1 for Escherichia coli and 0.05 for Staphylococcus aureus. It was then diluted with phosphate buffered saline (PBS) solution to a final concentration of 10 7 CFU.mL -1 . Place 50 μL of the diluted bacterial solution on a 1 cm × 1 cm film and incubate at 37°C for 6 hours. Then wash out the floating bacteria with PBS, dilute the washed bacterial solution several times and transfer it to the LB agar plate. After incubating at 37°C for 24 hours, count the colonies. The sterilization rate is calculated as follows:

[0048] Sterilization rate = (N B ~N A ) / N B ×100%, where N B is the colony count (CFU) of the negative control sample after 24 hours of culture, N A The colony count (CFU) of the modified sample after 24 hours of culture was obtained. Each sample was subjected to at least three biological independent replicates, with two technical replicates each time.

[0049] (2) Anti-bacterial adhesion test:

[0050] For antibacterial assay, the substrate was sterilized with 75% ethanol solution, rinsed with PBS, and then placed in a 12-well sterile plate. Subsequently, 3 mL of bacterial suspension was added to the wells and cultured at 37 ° C for a predetermined time (24 hours for Escherichia coli and 12 hours for Staphylococcus aureus) at 100 rpm. After the culture was completed, the sample was divided into two parts. The sample for testing the release characteristics was placed in a 1M NaCl solution and gently shaken for 10 minutes, then all samples were washed 3 times with sterile PBS and placed in the dark for 15 minutes using LIVE / DEAD BackLight Viability Kit (Thermo Fisher Scientific Inc.), rinsed with sterile PBS, and then observed using an Axio Observer A1 inverted fluorescence microscope.

[0051] (3) Cytocompatibility test:

[0052] The samples were sterilized by autoclaving at 121°C for 20 minutes. 2 / mL ratio was immersed in fresh HEM, and then incubated at 37 °C in a humidified atmosphere of 5% CO2 and 95% air for 24 hours before using the resulting solution. L929 cells were seeded into 96-well plates with 200 μL of fresh culture medium (MEM) at an initial cell density of 1 × 10 per well. 4 After 1 day of culture, each well of the 96-well plate was replaced with 200 μL of the obtained solution as the test group. The next day of incubation under the same culture conditions, the cell viability of the differential samples was evaluated by the CCK8 kit at an absorbance of 450 nm. The blank group using only the CCK8 solution and the fresh culture medium were used as negative controls. The cell viability (%) was calculated by the following formula:

[0053] Cell survival rate (%) = (B1-B0)(B2-B0)*100

[0054] Where: B1-absorbance of the test group; B2-absorbance of the negative control group; B0-absorbance of the blank control group. The experiment was performed in triplicate and repeated three times.

[0055] (4) Hemolysis test

[0056] Hemolysis assay was performed according to Table 2 of GB / T 16886.5-2003 and GB / T 14233.2-2005.

[0057] Fresh pig blood containing sodium citrate was provided by Beijing Bersee Technology Co., Ltd. (Beijing, China). 2 / mL ratio was immersed in sterile saline, and then incubated in an oscillator at 37°C for 24 hours and 200rpm. The resulting solution was stored at 4°C for use. Then 5mL of the test solution was added to a centrifuge tube. The test tube was positive with distilled water. The test tube was negative with sterile saline. 4.9mL of saline solution was added and incubated at 37°C for 30 minutes. After incubation, 100uL of fresh pig blood was added and incubated at 37°C for 1 hour. Finally, the sample was centrifuged at 3500 for 5 minutes, the supernatant was transferred, and the absorbance was measured at a wavelength of 545nm by an enzyme reader (Thermo Scientific Multiskan FC, America). The hemolysis rate (HR) was calculated by the following formula:

[0058] HR=(C-C0) / (C1-C0)

[0059] Where: C, C0 and C1 are the absorbance of the test group, the absorbance of the negative control group and the absorbance of the positive control group respectively. The experiment was performed in triplicate and repeated three times.

[0060] Embodiment 1:

[0061] (1) 25 parts of hyperbranched polyamide amine with a molecular weight of 30,000 were dissolved in 75 parts of ethanol, nitrogen was introduced into the reaction system for 30 minutes to exclude air, and then 7 parts of 2,3-epoxypropyltrimethylammonium chloride were added, and the mixture was stirred and heated at 60°C for 6 hours. Then 3 parts of methacryloyloxyethyl phosphorylcholine were added, and the mixture was stirred and heated at 60°C for 6 hours. Then 5 parts of fibrin adhesive were added, and the mixture was stirred and heated at 60°C for 6 hours. Finally, a cross-linkable multifunctional branched polymer was obtained, and the final primary amine content was 0.005 mol / g (calculated by acid-base titration).

[0062] (2) reacting 90 parts of the cross-linkable multifunctional branched polymer obtained in step (1) with a PBS solution of 10 parts of vancomycin at 60° C. for 12 hours, then dialyzing in PBS for 24 hours using a dialysis bag with a molecular weight cutoff of 8000, and finally obtaining a cross-linkable releasable multifunctional branched polymer;

[0063] (3) 30 parts of a cross-linkable and releasable multifunctional branched polymer and 70 parts of a terpolymer of methyl acrylate-ethyl acrylate-butyl acrylate are mixed in a solution and mechanically stirred at 80° C. for 24 hours to obtain a pre-cross-linked solution;

[0064] (4) spraying the pre-crosslinking solution obtained in step (3) on the surface of the polyurethane sheet at 60° C. for 15 seconds;

[0065] (5) Dry the sample in step (4) in a 60° C. forced air drying oven for 2 hours.

[0066] Example 2-4: The molecular weight of the hyperbranched polyamidoamine was adjusted, and the rest was the same as Example 1.

[0067] Comparative Example 1: A polyurethane sheet without any modification is used as Comparative Example 1.

[0068] Comparative Example 2: The polyurethane sheet was treated according to steps (1), (4) and (5) of Example 1.

[0069] Comparative Example 3: The polyurethane sheet was treated according to steps (1), (2), (4) and (5) of Example 1.

[0070] The polyurethane sheet with dual sterilization and anti-adhesion functions prepared in Example 14 and Comparative Example 13 was evaluated for sterilization performance, anti-adhesion performance and biosafety. The results are shown in Table 1 below:

[0071] Table 1 Bactericidal performance, anti-adhesion performance and biosafety evaluation table of Example 14 and Comparative Example 13

[0072]

[0073]

[0074] It can be seen from Example 14 and Comparative Example 13 that, compared with the polyurethane sheet without the addition of the cross-linkable and releasable multifunctional branched polymer, the dual sterilization-anti-stick composite cross-linked coating can give the polyurethane sheet excellent sterilization performance and excellent biosafety, and can also effectively inhibit the adhesion of living and dead bacteria. As the molecular weight of the hyperbranched polyamidoamine increases, the polyurethane sheet treated with the dual sterilization-anti-stick composite cross-linked coating has better sterilization performance, biosafety, and adhesion inhibition performance of living and dead bacteria.

[0075] Embodiment 5:

[0076] (1) 25 parts of hyperbranched polyamide amine with a molecular weight of 30,000 were dissolved in 75 parts of ethanol, nitrogen was introduced into the reaction system for 30 minutes to exclude air, and then 7 parts of 2,3-epoxypropyltrimethylammonium chloride were added, and the mixture was stirred and heated at 60°C for 6 hours. Then 3 parts of methacryloyloxyethyl phosphorylcholine were added, and the mixture was stirred and heated at 60°C for 6 hours. Then 5 parts of fibrin adhesive were added, and the mixture was stirred and heated at 60°C for 6 hours. Finally, a cross-linkable multifunctional branched polymer was obtained, and the final primary amine content was 0.02 mol / g (calculated by acid-base titration).

[0077] (2) reacting 90 parts of the cross-linkable multifunctional branched polymer obtained in step (1) with a PBS solution of 10 parts of vancomycin at 60° C. for 12 hours, then dialyzing in PBS for 24 hours using a dialysis bag with a molecular weight cutoff of 8000, and finally obtaining a cross-linkable releasable multifunctional branched polymer;

[0078] (3) 30 parts of a cross-linkable and releasable multifunctional branched polymer and 70 parts of a terpolymer of methyl acrylate-ethyl acrylate-butyl acrylate are mixed in a solution and mechanically stirred at 80° C. for 24 hours to obtain a pre-cross-linked solution;

[0079] (4) spraying the pre-crosslinking solution obtained in step (3) on the surface of the polyurethane sheet at 60° C. for 15 seconds;

[0080] (5) Dry the sample in step (4) in a 60° C. forced air drying oven for 2 hours.

[0081] Example 6-8: The content of the cross-linking active group amine of the cross-linkable multifunctional branched polymer was adjusted, and the rest was the same as Example 5.

[0082] Comparative Example 1: A polyurethane sheet without any modification is used as Comparative Example 1.

[0083] Comparative Example 4: The polyurethane sheet was treated according to steps (1), (4) and (5) of Example 5.

[0084] Comparative Example 5: The polyurethane sheet was treated according to steps (1), (2), (4) and (5) of Example 5.

[0085] The polyurethane sheets with dual sterilization and anti-adhesion functions prepared in Examples 5-8 and Comparative Examples 1, 4, and 5 were evaluated for sterilization performance, anti-adhesion performance, and biosafety. The results are shown in Table 2 below:

[0086] Table 2 Evaluation table of bactericidal performance, anti-adhesion performance and biosafety of Examples 5-8 and Comparative Examples 1, 4, 5

[0087]

[0088]

[0089] It can be seen from Examples 5-8 and Comparative Examples 1, 4, and 5 that, compared with polyurethane sheets without the addition of cross-linkable and releasable multifunctional branched polymers, the dual sterilization-anti-stick composite cross-linked coating can give the polyurethane sheets excellent sterilization performance and excellent biosafety, and can also effectively inhibit the adhesion of living and dead bacteria. As the content of the cross-linking active group amine group mol / g increases, the sterilization performance, biosafety, and adhesion inhibition performance of the polyurethane sheets treated with the dual sterilization-anti-stick composite cross-linked coating are better.

[0090] Embodiment 9:

[0091] (1) 25 parts of hyperbranched polyamide amine with a molecular weight of 30,000 were dissolved in 75 parts of ethanol, nitrogen was introduced into the reaction system for 30 minutes to exclude air, and then 7 parts of 2,3-epoxypropyltrimethylammonium chloride were added, and the mixture was stirred and heated at 60°C for 6 hours. Then 3 parts of methacryloyloxyethyl phosphorylcholine were added, and the mixture was stirred and heated at 60°C for 6 hours. Then 5 parts of fibrin adhesive were added, and the mixture was stirred and heated at 60°C for 6 hours. Finally, a cross-linkable multifunctional branched polymer was obtained, and the final primary amine content was 0.02 mol / g (calculated by acid-base titration).

[0092] (2) reacting 70 parts of the cross-linkable multifunctional branched polymer obtained in step (1) with 30 parts of a PBS solution of vancomycin at 60° C. for 12 hours, then dialyzing in PBS for 24 hours using a dialysis bag with a molecular weight cutoff of 8000, and finally obtaining a cross-linkable releasable multifunctional branched polymer;

[0093] (3) 30 parts of a cross-linkable and releasable multifunctional branched polymer and 70 parts of a terpolymer of methyl acrylate-ethyl acrylate-butyl acrylate are mixed in a solution and mechanically stirred at 80° C. for 24 hours to obtain a pre-cross-linked solution;

[0094] (4) spraying the pre-crosslinking solution obtained in step (3) on the surface of the polyurethane sheet at 60° C. for 15 seconds;

[0095] (5) Dry the sample in step (4) in a 60° C. forced air drying oven for 2 hours.

[0096] Examples 10-12: The amount of the release-type antibacterial agent was adjusted, and the rest was the same as Example 9.

[0097] Comparative Example 1: A polyurethane sheet without any modification is used as Comparative Example 1.

[0098] Comparative Example 6: The polyurethane sheet was treated according to steps (1), (4) and (5) of Example 9.

[0099] Comparative Example 7: The polyurethane sheet was treated according to steps (1), (2), (4) and (5) of Example 9.

[0100] The polyurethane sheets with dual sterilization and anti-adhesion functions prepared by Examples 9-12 and Comparative Examples 1, 6, and 7 were evaluated for sterilization performance, anti-adhesion performance, and biosafety. The results are shown in Table 3 below:

[0101] Table 3 Bactericidal performance, anti-adhesion performance and biosafety evaluation table of Examples 9-12 and Comparative Examples 1, 6, 7

[0102]

[0103] It can be seen from Examples 9-12 and Comparative Examples 1, 6, and 7 that, compared with polyurethane sheets without cross-linkable releasable multifunctional branched polymers, the dual bactericidal-anti-adhesive composite cross-linked coating can give the polyurethane sheets excellent bactericidal properties and excellent biosafety, and can also effectively inhibit the adhesion of living and dead bacteria. As the amount of the releasable antibacterial agent increases, the bactericidal properties, biosafety, and adhesion inhibition properties of the polyurethane sheets treated with the dual bactericidal-anti-adhesive composite cross-linked coating are better.

[0104] Embodiment 13:

[0105] (1) 25 parts of hyperbranched polyamide amine with a molecular weight of 30,000 were dissolved in 75 parts of ethanol, nitrogen was introduced into the reaction system for 30 minutes to exclude air, and then 7 parts of 2,3-epoxypropyltrimethylammonium chloride were added, and the mixture was stirred and heated at 60°C for 6 hours. Then 3 parts of methacryloyloxyethyl phosphorylcholine were added, and the mixture was stirred and heated at 60°C for 6 hours. Then 5 parts of fibrin adhesive were added, and the mixture was stirred and heated at 60°C for 6 hours. Finally, a cross-linkable multifunctional branched polymer was obtained, and the final primary amine content was 0.02 mol / g (calculated by acid-base titration).

[0106] (2) reacting 70 parts of the cross-linkable multifunctional branched polymer obtained in step (1) with 30 parts of a PBS solution of vancomycin at 60° C. for 12 hours, then dialyzing in PBS for 24 hours using a dialysis bag with a molecular weight cutoff of 8000, and finally obtaining a cross-linkable releasable multifunctional branched polymer;

[0107] (3) 5 parts of a cross-linkable and releasable multifunctional branched polymer and 95 parts of a terpolymer of methyl acrylate-ethyl acrylate-butyl acrylate were mixed in a solution and mechanically stirred at 80° C. for 24 hours to obtain a pre-cross-linked solution;

[0108] (4) spraying the pre-crosslinking solution obtained in step (3) on the surface of the polyurethane sheet at 60° C. for 15 seconds;

[0109] (5) Dry the sample in step (4) in a 60° C. forced air drying oven for 2 hours.

[0110] Examples 14-16: The pre-crosslinking content of the crosslinkable multifunctional branched polymer was adjusted, and the rest was the same as Example 13.

[0111] Comparative Example 1: A polyurethane sheet without any modification is used as Comparative Example 1.

[0112] Comparative Example 8: The polyurethane sheet was treated according to steps (1), (4) and (5) of Example 13.

[0113] Comparative Example 9: The polyurethane sheet was treated according to steps (1), (2), (4) and (5) of Example 13.

[0114] The polyurethane sheets with dual sterilization and anti-adhesion functions prepared by Examples 13-16 and Comparative Examples 1, 8, and 9 were evaluated for sterilization performance, anti-adhesion performance, and biosafety. The results are shown in the following table:

[0115] Table 4 Bactericidal performance, anti-adhesion performance and biosafety evaluation table of Examples 13-16 and Comparative Examples 1, 8, 9

[0116]

[0117] It can be seen from Examples 13-16 and Comparative Examples 1, 8, and 9 that, compared with polyurethane sheets without cross-linkable releasable multifunctional branched polymers, the dual sterilization-anti-stick composite cross-linked coating can give the polyurethane sheets excellent sterilization performance and excellent biosafety, and can also effectively inhibit the adhesion of living and dead bacteria. As the content of pre-crosslinked cross-linked multifunctional branched polymers increases, the sterilization performance, biosafety, and adhesion inhibition performance of polyurethane sheets treated with the dual sterilization-anti-stick composite cross-linked coating are better.

[0118] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A dual sterilization-anti-adhesion composite cross-linked coating, characterized in that The raw materials of the coating include 5-30 parts of cross-linkable release-type multifunctional branched polymer and 30-95 parts of cross-linkable functional polymer; The cross-linkable and releasable multifunctional branched polymer has a three-dimensional multi-active group branched polymer compound as the core, and is modified with reactive functional groups, antibacterial and antiviral functional groups, anti-adhesive functional groups, functional active molecular groups and releasable antibacterial active substances; The cross-linkable functional polymer is at least one of oil, oil processing product, cellulose derivative, natural resin, synthetic polyester, synthetic emulsion or its derivatives.

2. A dual sterilization-anti-adhesion composite cross-linked coating as claimed in claim 1, characterized in that: The molecular weight of the cross-linkable and releasable multifunctional branched polymer is 800-60000, preferably 20000-30000; the molar proportion of the reactive functional groups is 5-10%, the molar content of the antibacterial and antiviral functional groups is 30-50%, the molar content of the anti-adhesive functional groups is 20-50%, and the molar content of the functionally active molecular groups is 20-50%.

3. A dual sterilization-anti-adhesion composite cross-linked coating as claimed in claim 1, characterized in that: The three-dimensional multi-active group branched polymer compound is at least one of a multi-active group-containing hyperbranched polymer, a multi-active group-containing dendritic polymer or a derivative thereof; preferably at least one of a hyperbranched / dendritic polyamide amine, a hyperbranched polyethyleneimine, a hyperbranched polyamino acid, a hyperbranched polypeptide or a derivative thereof; more preferably at least one of a modified hyperbranched / dendritic polyamide amine, a modified hyperbranched polyethyleneimine, a modified hyperbranched polyamino acid, and a modified hyperbranched polypeptide; The reactive group is at least one of an amino group, a carboxyl group, a maleimide group, a N-hydroxysuccinimide group, an azide group, an alkynyl group, a thiol group, an aldehyde group, and a hydroxyl group; The antibacterial and antiviral functional group is at least one of quaternary ammonium salts, quaternary phosphonium salts, guanidines, halogenated phenols, halamines or their derivatives; The anti-stick functional group is at least one of propane sultone, acrylic acid, methacrylic acid, acryloxyphosphocholine, methacryloyloxyphosphocholine, acrylamidophosphocholine, methacryloylphosphocholine, acryloxysulfonic acid betaine, methacryloyloxysulfonic acid betaine, acrylamidosulfonic acid betaine, methacryloylsulfonic acid betaine, acrylamidosulfonic acid betaine, methacryloylsulfonic acid betaine, acryloxycarboxylic acid betaine, acrylamidocarboxylic acid betaine, methacryloylcarboxylic acid betaine, monopolyethylene glycol acrylate, monopolyethylene glycol methacrylate, hydroxyethyl acrylate, hydroxyethyl methacrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate, acrylamide, methacrylamide, vinyl pyrrolidone, styrene sulfonic acid and 2-acrylamide-2-methylpropane sulfonic acid or its derivatives; The functionally active molecular group is at least one of collagen, gelatin, fibrin adhesive, cellulose, starch, alginate, chitosan, agarose, hyaluronic acid or its derivatives; The releasable antibacterial active substance is at least one of tetracycline broad-spectrum antibiotics, biguanide compounds, aminoglycoside antibiotics, antibacterial polypeptides, nano-inorganic antibacterial agents, metal ions, plant-derived antibacterial agents or their derivatives, preferably at least one of antibacterial polypeptides, nano-inorganic antibacterial agents, metal ions, and plant-derived antibacterial agents.

4. A dual sterilization-anti-adhesion composite cross-linked coating as claimed in claim 1, characterized in that: The synthetic polyester is selected from at least one of polyvinyl alcohol, polybutylene terephthalate, polycarbonate, polyphenylene terephthalate-butylene terephthalate, polylactic acid polyester, and acrylic polymers; preferably, the functional polymer is at least one of acrylic polymers, polyurethane, polybutylene succinate, polybutylene terephthalate-adipate, polybutylene succinate-co-terephthalate, polybutylene succinate-adipate-butylene terephthalate, polycaprolactone, polypropylene carbonate, polyhydroxyalkanoic acid, polyhydroxybutyric acid-hexanoate, poly 3,4-hydroxybutyrate, cellulose ester, cellulose ether, cellulose carbamate, cellulose nitrate, cellulose sulfonate, chitosan, hyaluronic acid, alginic acid, agarose, collagen, silk fibroin, silk protein, gelatin, polyphenols, polypeptides, or derivatives thereof.

5. The method for preparing a dual sterilization-anti-adhesion composite cross-linked coating according to claim 1, characterized in that The following steps are involved: 1) Using three-dimensional multi-active group branched polymer compounds to prepare cross-linkable multifunctional branched polymers; 2) subjecting the cross-linkable multifunctional branched polymer obtained in step 1) to a composite reaction with a releasable antibacterial active substance, and then dialyzing to obtain a cross-linkable releasable multifunctional branched polymer; 3) pre-crosslinking the crosslinkable releasable multifunctional branched polymer obtained in step 2) with the crosslinkable functional polymer; 4) preparing a functional coating using the pre-crosslinked solution obtained in step 3); 5) Post-processing the sample of step 4) to obtain a dual sterilization-anti-adhesion composite cross-linked coating.

6. A dual sterilization-anti-adhesion composite cross-linked coating as claimed in claim 5, characterized in that The specific method in step 1) is: dissolving the three-dimensional multi-active group branched polymer compound in a solvent, wherein the solvent is at least one of water, ethanol, methanol, and acetone, and adding a compound containing antibacterial and antiviral functional groups, a compound containing anti-adhesive functional groups, and a functionally active molecular group substance respectively, removing the solvent after the reaction, and obtaining a cross-linkable multifunctional branched polymer.

7. The method for preparing a dual sterilization-anti-adhesion composite cross-linked coating according to claim 5, characterized in that In step 2), the mass proportion of the releasable antibacterial active substance is 5-10%; the conditions of the composite reaction are: temperature 20-80°C, reaction time 6-24 hours, dialysis bag molecular weight cutoff 8000-15000, dialysate is one of distilled water and PBS buffer solution, and dialysis time is 12-24 hours; preferably, the temperature is 30-70°C, the reaction time is 10-20 hours, the dialysis bag molecular weight cutoff is 10000-12000, and the dialysis time is 15-20 hours; The conditions for pre-crosslinking in step 3) are: temperature 60-80° C., reaction time 12-24 hours.

8. The method for preparing a dual sterilization-anti-adhesion composite cross-linked coating according to claim 5, characterized in that In step 4), the functional coating is prepared by dip coating, spin coating or spray coating, and the thickness of the functional coating is 500 nm-2 mm, preferably 10 μm-1 mm; The dipping conditions are: temperature 60-80°C, time 10-30 seconds; The spin coating conditions are: temperature 60-80° C., time 30-60 seconds; the spray coating conditions are: temperature 60-80° C., time 20-60 seconds.

9. The method for preparing a dual sterilization-anti-adhesion composite cross-linked coating according to claim 5, characterized in that In step 5), the post-treatment includes natural drying, vacuum drying, and solution phase transformation. The natural drying conditions are: room temperature, time 6-24 hours; the vacuum drying conditions are: temperature 25-60°C, time 6-12 hours; the solution phase transformation conditions are: temperature 15-37°C, time 15-30 minutes.

10. Use of the dual sterilization-anti-adhesion composite cross-linked coating according to claim 1 in the preparation of an antibacterial coating, wherein the application includes use as an antibacterial coating on the surfaces of various assets and commodities in public places and households.

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