A dual biocidal-anti-adhesion composite crosslinked coating and its preparation method and use

Abstract

The application relates to a dual sterilization-anti-adhesion composite crosslinking coating as well as a preparation method and application thereof, and belongs to the technical field of functional polymer materials. The raw materials of the coating include 5-30 parts of crosslinkable release type multifunctional branched polymer and 30-95 parts of crosslinkable functional polymer. The above-mentioned dual sterilization-anti-adhesion composite crosslinking coating can combine the advantages of contact sterilization, release of antibacterial factors and anti-adhesion together. On one hand, the super-hydrophilic component can effectively prevent the initial adhesion of bacteria and proteins. Even if a small amount of bacteria falls into the coating surface, the contact sterilization component can effectively kill the small amount of adhered bacteria, thereby avoiding the formation of bacteria and biofilms. In addition, the introduction of the releaseable antibacterial molecules can effectively enhance the antibacterial effect, so that the purpose of killing pathogenic bacteria in a deep level is achieved.

Description

Technical Field

[0001] This invention belongs to the field of functional polymer materials technology, specifically a dual bactericidal-anti-adhesive composite crosslinking coating, its preparation method, and its uses. Background Technology

[0002] In recent years, the demand for antimicrobial coatings has been increasing in public health, medical equipment, marine industry, textiles, and water purification systems. Antimicrobial coatings are materials that can uniformly cover and adhere well to the surface of an object to form a solid film. They possess protective, decorative, or special functions. Classified according to the dispersion state of the film-forming substances and pigments, they include solvent-based antimicrobial coatings, water-based antimicrobial coatings, powder antimicrobial coatings, and high-energy radiation-cured antimicrobial coatings. With societal development, antimicrobial needs exist in many areas, including daily life, buildings, ships, and circulating cooling water systems. Therefore, improving the antimicrobial function of antimicrobial coatings is one of the directions for the development of the coating industry. Antimicrobial coatings can be made by adding suitable and stable antimicrobial materials to the coating. These coatings can be directly applied to various materials and have attracted much attention due to their ease of use.

[0003] The most common methods include antibacterial adhesion, contact killing, release of antimicrobial agents, and bactericidal-release methods (ACS Appl. Mater. Interfaces 2021, 13, 18, 20921–20937). Antibacterial adhesion utilizes the hydration principle of hydrophilic coatings to resist protein adsorption and initial microbial adhesion, thereby preventing bacteria from forming biofilms on material surfaces to a certain extent. For example, invention patent CN 113881086A utilizes a copolymer of bornyl acrylate (BA) and polyethylene glycol diacrylate (PEGDA) to construct an amphiphilic stereochemical polymer coating with antimicrobial adhesion properties. However, such anti-adhesion coatings cannot kill bacteria, nor can they completely prevent bacterial attachment; a small number of adhered bacteria will slowly accumulate and eventually form a biofilm. Contact killing coating strategies kill bacteria through contact sterilization or by blocking key metabolic or reproductive pathways, thereby inhibiting bacterial biofilm formation. For example, cationic polymers, a widely used type of antibacterial material, achieve their antibacterial effect by disrupting the cell walls / membranes of microorganisms. However, these bactericidal materials cannot effectively release antibacterial components, resulting in limited bactericidal performance. The release-based antibacterial agent method combines cationic polymers with releaseable nanoparticles to achieve contact and release-based bactericidal action. For instance, invention patent CN105999407A uses chitosan, silver nitrate, and polyvinyl alcohol as raw materials to prepare an antibacterial composite gel coating. Silver nanoparticles can achieve highly efficient bactericidal action through contact and silver ion release mechanisms, thus greatly improving bactericidal performance. However, a drawback of this bactericidal strategy is that killed bacteria and debris accumulate on the surface, covering the coating and thus losing its surface bactericidal function. A more popular approach is the bactericidal-release method, which utilizes the contact antibacterial mechanism of cationic polymers to disrupt the cell walls / membranes of microorganisms, while also employing the hydration principle of a superhydrophilic coating to resist the adhesion of proteins, bacteria, or the remains of killed bacteria. For example, invention patent CN112048223A uses responsive monomers and antifouling monomers to prepare antifouling-release microgel spheres or responsive polymer brushes, and then combines them with catechol polymers and Fe... 3+Solution co-precipitation yields an antibacterial surface with a multifunctional response of "antifouling-bactericidal-release". CN 109232834 A uses responsive monomers and antifouling 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 a multifunctional response of "antifouling-bactericidal-release". CN110484062B is a method for constructing an "antifouling-bactericidal-release" surface coating using dopamine, namely, adding the stimuli-responsive polymer, bactericidal polymer and antifouling polymer containing epoxy groups to a dopamine solution, and then co-depositing them on a substrate. Invention patent CN108755145A utilizes the superhydrophobicity of vinyl silicone oil to reduce bacterial adhesion, making it easier to remove bacteria attached to the material surface. It also utilizes the property of amphiphilic vinyl nitrogen-containing compounds that can act on the cell membrane and cause the release of intracellular substances to inhibit bacterial growth, thereby achieving the purpose of inhibiting bacterial adhesion and reproduction. Invention patent CN105646928A utilizes the thermodynamic spontaneous reaction between the active ester end group of N-hydroxysuccinimide and the primary amine group of collagen to prepare a material that can kill bacteria and prevent the adhesion of bacteria and other microorganisms. CN108299667B utilizes polyimide salts and anti-protein adhesion structural units grafted onto the surface of polymer materials via free radical reaction. Through the effect of surface charge, it inhibits the normal physiological function of bacterial cell membranes, thereby inhibiting bacterial reproduction and achieving antibacterial and anti-protein adhesion. CN110330658A mixes responsive monomers and epoxy monomers and performs a free radical copolymerization reaction, then mixes them with an epoxy-containing hydrophilic polymer and dissolves them in a solvent. An amino-containing bactericide is added to perform an epoxy ring-opening reaction to obtain an antibacterial hydrogel with bactericidal, low bacterial adhesion, and bacterial release properties. CN112048224B utilizes free radical polymerization to prepare responsive microgel spheres, then co-deposits the prepared microgel spheres, catechol derivatives, and metal bactericides onto a substrate to obtain an antibacterial surface with dual bactericidal and release functions. While "sterilization-release" surfaces combine the advantages of contact antibacterial and antibacterial adhesion, their antibacterial efficiency and long-lasting antibacterial effect are affected, thus limiting their application range. Furthermore, the construction of such coatings typically employs chemical grafting methods, a cumbersome process requiring large amounts of organic reagents, which can lead to environmental pollution. Summary of the Invention

[0004] To address the aforementioned problems in the existing technology, the purpose of this application is to design and provide a technical solution for a dual bactericidal-anti-adhesion composite cross-linking coating, its preparation method, and its applications. This solution combines 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 number of bacteria fall onto the coating surface, the contact sterilization component can effectively kill the small number of adhering bacteria, thereby preventing the formation of bacteria and biofilms. In addition, the introduction of releaseable antibacterial molecules can effectively enhance the antibacterial effect, achieving the purpose of deep-level killing of pathogens and overcoming the shortcomings of the existing technology, such as unsatisfactory bactericidal effect of antibacterial surfaces and inability to remove dead bacteria.

[0005] The dual bactericidal-anti-sticky composite crosslinking coating is characterized in that the raw materials of the coating include 5-30 parts of crosslinkable release multifunctional branched polymer and 30-95 parts of crosslinkable functional polymer;

[0006] The crosslinkable release-type multifunctional branched polymer is based on a three-dimensional multi-active group branched polymer compound, which is modified by reactive functional groups, antibacterial and antiviral functional groups, anti-adhesion functional groups, functional active molecular groups and release-type antibacterial active substances.

[0007] The crosslinkable functional polymer is at least one of oils, oil-processed products, cellulose derivatives, natural resins, synthetic polyesters, synthetic emulsions, or their derivatives.

[0008] The dual bactericidal-anti-sticking composite crosslinking coating is characterized in that: the molecular weight of the crosslinkable release-type multifunctional branched polymer is 800-60000, preferably 20000-30000; the elemental molar percentage 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-sticking functional groups is 20-50%, and the molar content of the functional active molecular groups is 20-50%.

[0009] The dual bactericidal-anti-sticking composite crosslinking 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 a derivative thereof; preferably at least one of hyperbranched / dendritic polyamide amine, hyperbranched polyethyleneimine, hyperbranched polyamino acid, hyperbranched polypeptide, or a derivative thereof; more preferably at least one of modified hyperbranched / dendritic polyamide amine, modified hyperbranched polyethyleneimine, modified hyperbranched polyamino acid, or modified hyperbranched polypeptide;

[0010] The reactive group is at least one selected from amino group, carboxyl group, maleimide, N-hydroxysuccinimide, azide, alkynyl group, mercapto group, aldehyde group, and hydroxyl group;

[0011] The antibacterial and antiviral functional groups are at least one of quaternary ammonium salts, quaternary phosphonium salts, guanidines, halogenated phenols, halogenated amines, or their derivatives.

[0012] The anti-adhesion functional group is at least one of the following: propanelactone, acrylic acid, methacrylic acid, acryloyloxyphosphocholine, methacryloyloxyphosphocholine, acrylamide phosphocholine, methacryloamide phosphocholine, acryloyloxysulfonate betaine, methacryloyloxysulfonate betaine, acrylamide sulfonate betaine, methacryloamide sulfonate betaine, acryloyloxycarboxylic acid betaine, acrylamide carboxylic acid betaine, methacryloamide carboxylic acid betaine, polyethylene glycol monoacrylate, polyethylene glycol monomethacrylate, hydroxyethyl acrylate, hydroxyethyl methacrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate, acrylamide, methacrylamide, vinylpyrrolidone, styrene sulfonic acid, and 2-acrylamido-2-methylpropanesulfonic acid or its derivatives.

[0013] The functional active molecular groups are at least one of collagen, gelatin, fibrin adhesive, cellulose, starch, alginate, chitosan, agarose, hyaluronic acid, or their derivatives.

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

[0015] The dual-sterilizing-anti-sticking composite crosslinking coating is characterized in that: the synthetic polyester is selected from at least one of polyvinyl alcohol ester, polybutylene terephthalate, polycarbonate, poly(terephthalone-butylene terephthalate), polylactic acid polyester, and acrylate polymers; preferably, the functional polymer is at least one of acrylate polymers, polyurethane, polybutylene succinate, polybutylene terephthalate-adipate, polybutylene succinate-co-butylene terephthalate, polybutylene succinate-adipate-butylene glycol ester, polycaprolactone, polypropylene carbonate, polyhydroxyalkanoic acid, polyhydroxybutyrate-hexanoate, poly3,4-hydroxybutyrate, cellulose ether, cellulose carbamate, cellulose nitrate, cellulose sulfonate, chitosan, hyaluronic acid, alginate, agarose, collagen, silk fibroin, silk protein, gelatin, polyphenols, polypeptides, or their derivatives.

[0016] The method for preparing a dual bactericidal-anti-sticky composite crosslinking coating is characterized by comprising the following steps:

[0017] 1) Preparation of crosslinkable multifunctional branched polymers using three-dimensional multi-active branched polymer compounds;

[0018] 2) The crosslinkable multifunctional branched polymer obtained in step 1) is combined with a release-type antibacterial active substance and then dialyzed to obtain the crosslinkable release-type multifunctional branched polymer.

[0019] 3) Pre-crosslink the crosslinkable release multifunctional branched polymer obtained in step 2) with the crosslinkable functional polymer;

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

[0021] 5) Post-process the sample from step 4) to obtain a dual sterilization-anti-adhesion composite cross-linking coating.

[0022] The dual bactericidal-anti-adhesive composite crosslinking coating is characterized in that the specific method in step 1) is as follows: a three-dimensional multi-active branched polymer compound is dissolved in a solvent, wherein the solvent is at least one of water, ethanol, methanol, and acetone, and compounds containing antibacterial and antiviral functional groups, compounds containing anti-adhesive functional groups, and functional active molecular groups are added respectively. After the reaction, the solvent is removed to obtain a crosslinkable multifunctional branched polymer.

[0023] The method for preparing a dual bactericidal-anti-adhesive composite crosslinking coating is characterized in that, in step 2), the mass percentage of the releasing antibacterial active substance is 5-10%; the conditions for the composite reaction are: temperature 20-80℃, reaction time 6-24 hours, molecular weight cutoff of the dialysis bag 8000-15000, dialysis solution is one of distilled water and PBS buffer solution, and dialysis time 12-24 hours; preferably, the temperature is 30-70℃, the reaction time is 10-20 hours, the molecular weight cutoff of the dialysis bag is 10000-12000, and the dialysis time is 15-20 hours.

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

[0025] The method for preparing a dual bactericidal-anti-adhesive composite crosslinking 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℃, time 10-30 seconds;

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

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

[0029] The application of the aforementioned dual bactericidal-anti-adhesive composite crosslinking coating in the preparation of antibacterial coatings includes its use as an antibacterial coating on the surfaces of various assets and goods in public places and homes.

[0030] Specifically, the antibacterial coating of the present invention can be applied to public places such as medical facilities, schools, changing rooms, restaurants, bank ATMs, communication equipment and public transportation. The antibacterial coating can be applied to the ventilation system, ceiling, pipes, surface protection of metal walls and various metal facilities in public places, and can inhibit the residue and growth of bacteria in equipment and facilities in these places.

[0031] Pregnant women, infants, and children are relatively vulnerable to bacteria and viruses. Using antibacterial coatings in homes with pregnant women or children can help protect them from bacteria and mold. Therefore, applying antibacterial coatings to home appliances, doors, windows, and steel furniture is of great practical significance.

[0032] Antibacterial coatings can be applied to surfaces such as glass, fiberglass, plastic, metal, wood, ceramics, composite materials, and natural materials. They can be used in air conditioners, furnace air filters, automobiles, air purification devices, aquarium filters, circulating air handling units, vehicle parts, etc.

[0033] Roofing materials include granules, sway, head, felt, padding, membrane, ceramic tiles and synthetic exterior antibacterial coatings; building materials include wood composites, wall panels, timber, siding, stainless steel, cabinets and insulation materials, ceilings, conveyors, concrete products and other exterior antibacterial coatings.

[0034] Antimicrobial coatings can be applied to various surfaces, such as floor coverings, healthcare facilities, fiberglass piping, general containers, non-food contact tops, furniture, bathroom fixtures, mats, plumbing supplies, vacuum cleaners and filters, sheets, foam for cushioning and packaging, and more.

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

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

[0037] 2) Three-dimensional branched polymers with multiple active groups are highly designable, with molecular particle sizes ranging from a few nanometers to tens of nanometers. Their internal cavities allow them to serve as carriers for nanomedicines or to encapsulate a specific number of drug molecules, achieving drug loading and controlled release, thus enabling deep-level elimination of pathogenic microorganisms.

[0038] 3) Three-dimensional multi-active branched polymers can provide more terminal active functional groups, can combine more functional groups, and can form more cross-linking sites with functional polymers. This can achieve stable intralayer and interlayer cross-linking between the coating and the substrate, thus having better long-term stability.

[0039] 4) The resulting dual-bacterial and anti-adhesion composite cross-linked coating not only utilizes the functional groups of cross-linkable, release-type multifunctional branched polymers to kill pathogenic microorganisms that fall onto the coating surface, but also leverages the strong hydration of superhydrophilic components to prevent bacterial carcasses and proteins from adhering to its surface, thus achieving anti-adhesion. Furthermore, the antibacterial active substances loaded within the cavity can kill pathogenic microorganisms at a deeper level, achieving a longer-lasting, broader-spectrum, and more durable antibacterial effect.

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

[0041] 6) The resulting dual bactericidal-anti-adhesive composite cross-linking coating is applicable to almost any substrate material, has universality, and does not damage the substrate material, protecting the structural properties of the substrate material, which is conducive to industrial production. Attached Figure Description

[0042] Figure 1 This is a schematic diagram of the crosslinkable release multifunctional branched polymer of the present invention;

[0043] Figure 2 This is a schematic diagram illustrating the preparation of the dual bactericidal-anti-adhesive composite crosslinking coating of the present invention. Detailed Implementation

[0044] The present invention will be clearly and completely described below with reference to the accompanying drawings and specific embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0045] The experimental testing methods used in this invention are as follows:

[0046] (1) Sterilization performance test:

[0047] The antifouling, bactericidal, and regenerability of polymer surfaces were tested using *Escherichia coli* (Gram-negative bacteria) and *Staphylococcus aureus* (Gram-positive bacteria). Both bacteria were first incubated overnight on Luria-Bertani (LB) agar at 37°C. Bacterial colonies were then inoculated into 40 mL of LB medium and shaken at 37°C for 10 hours. The bacterial solutions were diluted with pure LB to OD values ​​of 0.1 for *E. coli* and 0.05 for *Staphylococcus aureus*. These were then diluted with phosphate-buffered saline (PBS) to achieve a final bacterial concentration on the order of 10. 7 CFU.mL -1 50 μL of the diluted bacterial solution was placed on a 1 cm × 1 cm membrane and incubated at 37°C for 6 hours. Airborne bacteria were then eluted with PBS. The eluted bacterial solution was repeatedly diluted and transferred to LB agar plates, incubated at 37°C for 24 hours, and colony counting was performed. The sterilization rate was calculated as follows:

[0048] Sterilization rate = (N) B ~N A ) / N B ×100%, where N B The number of colonies (CFU) in the negative control sample after 24 hours of incubation is N. A The colony count (CFU) of the modified sample after 24 hours of incubation. Each sample should be performed in at least three biologically independent replicates, with two techniques used for each replicate.

[0049] (2) Antibacterial adhesion test:

[0050] For antimicrobial assays, the substrate was sterilized with 75% ethanol and rinsed with PBS before being placed in 12-well sterile plates. Subsequently, 3 mL of bacterial suspension was added to each well and the plates were incubated at 37°C for the predetermined time (24 hours for *E. coli* and 12 hours for *Staphylococcus aureus*) at 100 rpm. After incubation, the samples were divided into two portions. The sample used to test release characteristics was placed in 1M NaCl solution and gently shaken for 10 minutes. All samples were then washed three times with sterile PBS and placed in the dark for 15 minutes using a LIVE / DEAD BackLight Viability Kit (Thermo Fisher Scientific Inc.). After rinsing with sterile PBS, the samples were observed using an Axio Observer A1 inverted fluorescence microscope.

[0051] (3) Cell compatibility test:

[0052] The samples were autoclaved at 121°C for 20 minutes. Afterwards, the samples were placed at a depth of 6 cm. 2 Immerse the cells in fresh HEM at a ratio of 1 / mL, then incubate at 37°C for 24 hours in a humid atmosphere of 5% CO2 and 95% air, and then use the resulting solution. Seed L929 cells in 200 μL of fresh MEM medium into 96-well plates at an initial cell density of 1 × 10⁶ cells per well. 4 After culturing for 1 day, each well of a 96-well plate was replaced with 200 μL of the resulting solution as the test group. On the second day of incubation under the same culture conditions, cell viability of the differentially expressed samples was assessed using a CCK8 kit at an absorbance of 450 nm. A blank group using only CCK8 solution was included, with fresh culture medium serving as a negative control. Cell viability (%) was calculated using the following formula:

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

[0054] Wherein: 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 was determined according to Table 2 of GB / T 16886.5-2003 and GB / T 14233.2-2005. Fresh pig blood containing sodium citrate was provided by Beijing Bersee Technology Co., Ltd. (Beijing, China). First, the sample was placed at a depth of 6 cm... 2Immerse the sample in sterile saline at a ratio of 1 / mL, then incubate at 37°C for 24 hours at 200 rpm. Store the resulting solution at 4°C for use. Then add 5 mL of test solution to centrifuge tubes. The tubes with distilled water are for the positive group. The tubes with sterile saline are for the negative group. Add 4.9 mL of saline solution and incubate at 37°C for 30 minutes. After incubation, add 100 μL of fresh pig blood and incubate at 37°C for 1 hour. Finally, centrifuge the sample at 3500 rpm for 5 minutes, transfer the supernatant, and measure the absorbance at 545 nm using a microplate reader (Thermo Scientific Multiskan FC, America). Calculate the hemolysis rate (HR) using the following formula: HR = (C-C0) / (C1-C0).

[0057] Wherein: C, C0, and C1 are the absorbance of the test group, the negative control group, and the positive control group, respectively. The experiment was performed in triplicate and repeated three times.

[0058] Example 1:

[0059] 25 parts of hyperbranched polyamide amine with a molecular weight of 30,000 were dissolved in 75 parts of ethanol. Nitrogen gas was bubbled into the reaction system for 30 minutes to purge air. Then, 7 parts of 2,3-epoxypropyltrimethylammonium chloride were added, and the reaction was carried out at 60°C with stirring and heating for 6 hours. Next, 3 parts of methacryloxyethyl phosphocholine were added, and the reaction was carried out at 60°C with stirring and heating for 6 hours. Finally, 5 parts of fibrin binder were added, and the reaction was carried out at 60°C with stirring and heating for 6 hours. The final crosslinkable multifunctional branched polymer was obtained, with a final primary amine content of 0.005 mol / g (calculated by acid-base titration).

[0060] (2) 90 parts of the crosslinkable multifunctional branched polymer obtained in step (1) were reacted with 10 parts of vancomycin in PBS solution at 60°C for 12 hours. Then, the polymer was dialyzed in PBS for 24 hours using a dialysis bag with a molecular weight cutoff of 8000. Finally, the crosslinkable release type multifunctional branched polymer was obtained.

[0061] (3) 30 parts of crosslinkable release multifunctional branched polymer and 70 parts of methyl acrylate-ethyl acrylate-butyl acrylate terpolymer were solution blended and mechanically stirred at 80°C for 24 hours to obtain a pre-crosslinked solution;

[0062] (4) The pre-crosslinking solution obtained in step (3) is sprayed onto the surface of the polyurethane board at 60°C for 15 seconds.

[0063] (5) Dry the sample from step (4) in a 60°C forced-air drying oven for 2 hours.

[0064] Examples 2-4: The molecular weight of hyperbranched polyamide amine was adjusted, and the rest was the same as in Example 1.

[0065] Comparative Example 1: An unmodified polyurethane board was used as Comparative Example 1.

[0066] Comparative Example 2: The polyurethane board was treated according to steps (1), (4), and (5) of Example 1.

[0067] Comparative Example 3: The polyurethane board was treated according to steps (1), (2), (4), and (5) of Example 1.

[0068] The bactericidal performance, anti-adhesion performance, and biosafety of the polyurethane boards with dual bactericidal-anti-adhesion functions prepared by Examples 1-4 and Comparative Examples 1-3 were evaluated, and the results are shown in Table 1 below:

[0069]

[0070] As shown in Examples 1-4 and Comparative Examples 1-3, compared to polyurethane boards without the addition of crosslinkable release multifunctional branched polymers, the dual bactericidal-anti-adhesion composite crosslinking coating can impart excellent bactericidal properties and superior biocompatibility to polyurethane boards, and can also effectively inhibit the adhesion of live and dead bacteria. With the increase of the molecular weight of hyperbranched polyamide amine, the bactericidal properties, biocompatibility, and inhibition of live and dead bacteria adhesion of the polyurethane boards treated with the dual bactericidal-anti-adhesion composite crosslinking coating are even better.

[0071] Example 5:

[0072] (1) 25 parts of hyperbranched polyamide amine with a molecular weight of 30,000 were dissolved in 75 parts of ethanol. Nitrogen gas was introduced into the reaction system for 30 minutes to remove air. Then, 7 parts of 2,3-epoxypropyltrimethylammonium chloride were added, and the reaction was carried out at 60°C with stirring and heating for 6 hours. Then, 3 parts of methacryloyloxyethyl phosphocholine were added, and the reaction was carried out at 60°C with stirring and heating for 6 hours. Then, 5 parts of fibrin binder were added, and the reaction was carried out at 60°C with stirring and heating for 6 hours. Finally, a crosslinkable multifunctional branched polymer was obtained, and the final primary amine content was 0.02 mol / g (calculated by acid-base titration).

[0073] (2) 90 parts of the crosslinkable multifunctional branched polymer obtained in step (1) were reacted with 10 parts of vancomycin in PBS solution at 60°C for 12 hours. Then, the polymer was dialyzed in PBS for 24 hours using a dialysis bag with a molecular weight cutoff of 8000. Finally, the crosslinkable release type multifunctional branched polymer was obtained.

[0074] (3) 30 parts of crosslinkable release multifunctional branched polymer and 70 parts of methyl acrylate-ethyl acrylate-butyl acrylate terpolymer were solution blended and mechanically stirred at 80°C for 24 hours to obtain a pre-crosslinked solution;

[0075] (4) The pre-crosslinking solution obtained in step (3) is sprayed onto the surface of the polyurethane board at 60°C for 15 seconds.

[0076] (5) Dry the sample from step (4) in a 60°C forced-air drying oven for 2 hours.

[0077] Examples 6-8: The content of crosslinking active amine groups in the crosslinkable multifunctional branched polymer was adjusted, and the rest was the same as in Example 5.

[0078] Comparative Example 1: An unmodified polyurethane board was used as Comparative Example 1.

[0079] Comparative Example 4: The polyurethane board was treated according to steps (1), (4), and (5) of Example 5.

[0080] Comparative Example 5: The polyurethane board was treated according to steps (1), (2), (4), and (5) of Example 5.

[0081] The bactericidal, anti-adhesion, and biosafety properties of the polyurethane boards with dual bactericidal-anti-adhesion functions prepared by Examples 5-8 and Comparative Examples 1, 4, and 5 were evaluated, and the results are shown in Table 2 below:

[0082]

[0083] As demonstrated in Examples 5-8 and Comparative Examples 1, 4, and 5, compared to polyurethane boards without the addition of crosslinkable release multifunctional branched polymers, the dual-sterilization-anti-adhesion composite crosslinking coating imparts excellent bactericidal properties and superior biocompatibility to the polyurethane boards, and effectively inhibits the adhesion of both live and dead bacteria. With the increase of the content (mol / g) of the crosslinking active amino groups, the polyurethane boards treated with the dual-sterilization-anti-adhesion composite crosslinking coating exhibit better bactericidal properties, biocompatibility, and inhibition of live and dead bacteria adhesion.

[0084] Example 9:

[0085] (1) 25 parts of hyperbranched polyamide amine with a molecular weight of 30,000 were dissolved in 75 parts of ethanol. Nitrogen gas was introduced into the reaction system for 30 minutes to remove air. Then, 7 parts of 2,3-epoxypropyltrimethylammonium chloride were added, and the reaction was carried out at 60°C with stirring and heating for 6 hours. Then, 3 parts of methacryloyloxyethyl phosphocholine were added, and the reaction was carried out at 60°C with stirring and heating for 6 hours. Then, 5 parts of fibrin binder were added, and the reaction was carried out at 60°C with stirring and heating for 6 hours. Finally, a crosslinkable multifunctional branched polymer was obtained, and the final primary amine content was 0.02 mol / g (calculated by acid-base titration).

[0086] (2) 70 parts of the crosslinkable multifunctional branched polymer obtained in step (1) and 30 parts of vancomycin in PBS solution were reacted at 60°C for 12 hours. Then, the polymer was dialyzed in PBS for 24 hours using a dialysis bag with a molecular weight cutoff of 8000. Finally, the crosslinkable release type multifunctional branched polymer was obtained.

[0087] (3) 30 parts of crosslinkable release multifunctional branched polymer and 70 parts of methyl acrylate-ethyl acrylate-butyl acrylate terpolymer were solution blended and mechanically stirred at 80°C for 24 hours to obtain a pre-crosslinked solution;

[0088] (4) The pre-crosslinking solution obtained in step (3) is sprayed onto the surface of the polyurethane board at 60°C for 15 seconds.

[0089] (5) Dry the sample from step (4) in a 60°C forced-air drying oven for 2 hours.

[0090] Examples 10-12: The amount of the release-type antibacterial agent was adjusted, and the rest was the same as in Example 9.

[0091] Comparative Example 1: An unmodified polyurethane board was used as Comparative Example 1.

[0092] Comparative Example 6: The polyurethane board was treated according to steps (1), (4), and (5) of Example 9.

[0093] Comparative Example 7: The polyurethane board was treated according to steps (1), (2), (4), and (5) of Example 9.

[0094] The bactericidal, anti-adhesion, and biosafety properties of the polyurethane sheets with dual bactericidal and anti-adhesion functions prepared by Examples 9-12 and Comparative Examples 1, 6, and 7 were evaluated, and the results are shown in Table 3 below:

[0095]

[0096] As demonstrated in Examples 9-12 and Comparative Examples 1, 6, and 7, compared to polyurethane boards without the addition of crosslinkable release-type multifunctional branched polymers, the dual bactericidal-anti-adhesion composite crosslinking coating imparts excellent bactericidal properties and superior biocompatibility to the polyurethane boards, and effectively inhibits the adhesion of both live and dead bacteria. With increasing amounts of release-type antibacterial agent, the polyurethane boards treated with the dual bactericidal-anti-adhesion composite crosslinking coating exhibit better bactericidal properties, biocompatibility, and inhibition of live and dead bacteria adhesion.

[0097] Example 13:

[0098] (1) 25 parts of hyperbranched polyamide amine with a molecular weight of 30,000 were dissolved in 75 parts of ethanol. Nitrogen gas was introduced into the reaction system for 30 minutes to remove air. Then, 7 parts of 2,3-epoxypropyltrimethylammonium chloride were added, and the reaction was carried out at 60°C with stirring and heating for 6 hours. Then, 3 parts of methacryloyloxyethyl phosphocholine were added, and the reaction was carried out at 60°C with stirring and heating for 6 hours. Then, 5 parts of fibrin binder were added, and the reaction was carried out at 60°C with stirring and heating for 6 hours. Finally, a crosslinkable multifunctional branched polymer was obtained, and the final primary amine content was 0.02 mol / g (calculated by acid-base titration).

[0099] (2) 70 parts of the crosslinkable multifunctional branched polymer obtained in step (1) and 30 parts of vancomycin in PBS solution were reacted at 60°C for 12 hours. Then, the polymer was dialyzed in PBS for 24 hours using a dialysis bag with a molecular weight cutoff of 8000. Finally, the crosslinkable release type multifunctional branched polymer was obtained.

[0100] (3) Five parts of crosslinkable release multifunctional branched polymer and 95 parts of methyl acrylate-ethyl acrylate-butyl acrylate terpolymer were solution blended and mechanically stirred at 80°C for 24 hours to obtain a pre-crosslinked solution;

[0101] (4) The pre-crosslinking solution obtained in step (3) is sprayed onto the surface of the polyurethane board at 60°C for 15 seconds.

[0102] (5) Dry the sample from step (4) in a 60°C forced-air drying oven for 2 hours.

[0103] Examples 14-16: The content of the crosslinkable multifunctional branched polymer precrosslinked was adjusted, and the rest was the same as in Example 13.

[0104] Comparative Example 1: An unmodified polyurethane board was used as Comparative Example 1.

[0105] Comparative Example 8: The polyurethane board was treated according to steps (1), (4), and (5) of Example 13.

[0106] Comparative Example 9: The polyurethane board was treated according to steps (1), (2), (4), and (5) of Example 13.

[0107] The bactericidal, anti-adhesion, and biosafety properties of the polyurethane sheets with dual bactericidal and anti-adhesion functions prepared in Examples 13-16 and Comparative Examples 1, 8, and 9 were evaluated, and the results are shown in the table below:

[0108]

[0109] As demonstrated in Examples 13-16 and Comparative Examples 1, 8, and 9, compared to polyurethane boards without the addition of crosslinkable release multifunctional branched polymers, the dual bactericidal-anti-adhesion composite crosslinking coating imparts excellent bactericidal properties and superior biocompatibility to the polyurethane boards, and effectively inhibits the adhesion of both live and dead bacteria. The higher the content of the pre-crosslinked crosslinkable multifunctional branched polymer, the better the bactericidal properties, biocompatibility, and inhibition of live and dead bacteria adhesion of the polyurethane boards treated with the dual bactericidal-anti-adhesion composite crosslinking coating.

[0110] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A dual-sterilizing-anti-sticking composite cross-linking coating, characterized in that... The raw materials for this coating include 5-30 parts of crosslinkable release-type multifunctional branched polymer and 30-95 parts of crosslinkable functional polymer; The crosslinkable release-type multifunctional branched polymer is obtained by modifying a three-dimensional multi-active group branched polymer compound with reactive functional groups, antibacterial and antiviral functional groups, anti-adhesion functional groups, functional active molecular groups and release-type antibacterial active substances. The crosslinkable functional polymer is at least one of oils, cellulose derivatives, natural resins, synthetic polyesters, synthetic emulsions, or their derivatives. The three-dimensional multi-active group branched polymer compound is at least one of the following: hyperbranched polymer containing multi-active groups, dendritic polymer containing multi-active groups, or derivatives thereof; The reactive functional group is at least one selected from amino, carboxyl, maleimide, N-hydroxysuccinimide, azide, alkynyl, mercapto, aldehyde, and hydroxyl groups. The antibacterial and antiviral functional groups are at least one of quaternary ammonium salts, quaternary phosphonium salts, guanidines, halogenated phenols, halogenated amines, or their derivatives. The anti-adhesion functional group is at least one of the following: propanelactone, acrylic acid, methacrylic acid, acryloyloxyphosphocholine, methacryloyloxyphosphocholine, acrylamide phosphocholine, methacryloamide phosphocholine, acryloyloxysulfonate betaine, methacryloyloxysulfonate betaine, acrylamide sulfonate betaine, methacryloamide sulfonate betaine, acryloyloxycarboxylic acid betaine, acrylamide carboxylic acid betaine, methacryloamide carboxylic acid betaine, polyethylene glycol monoacrylate, polyethylene glycol monomethacrylate, hydroxyethyl acrylate, hydroxyethyl methacrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate, acrylamide, methacrylamide, vinylpyrrolidone, styrene sulfonic acid, and 2-acrylamido-2-methylpropanesulfonic acid or its derivatives. The functional active molecular groups are at least one of collagen, gelatin, fibrin adhesive, cellulose, starch, alginate, chitosan, agarose, hyaluronic acid, or their derivatives. The released antibacterial active substance is at least one of the following: tetracycline broad-spectrum antibiotics, biguanide compounds, aminoglycoside antibiotics, antibacterial peptides, nano-inorganic antibacterial agents, metal ions, plant-derived antibacterial agents, or their derivatives.

2. The dual bactericidal-anti-sticking composite crosslinking coating as described in claim 1, characterized in that: The crosslinkable release-type multifunctional branched polymer has a molecular weight of 800-60000; the elemental molar percentage of the reactive functional groups is 5-10%, the molar content of antibacterial and antiviral functional groups is 30-50%, the molar content of anti-adhesion functional groups is 20-50%, and the molar content of functional active molecular groups is 20-50%.

3. The dual bactericidal-anti-sticking composite crosslinking coating as described in claim 1, characterized in that: The three-dimensional multi-active branched polymer compound is at least one of hyperbranched / dendritic polyamide amine, hyperbranched polyethyleneimine, hyperbranched polyamino acid, hyperbranched clustered peptide or its derivatives; The aforementioned release-type antibacterial active substance is at least one of antibacterial peptides, nano-inorganic antibacterial agents, metal ions, and plant-derived antibacterial agents.

4. The dual bactericidal-anti-sticking composite crosslinking coating as described in claim 1, characterized in that: The synthetic polyester is selected from at least one of polyvinyl alcohol ester, polybutylene terephthalate, polycarbonate, polybutylene terephthalate, polylactic acid polyester, and acrylate polymers.

5. The dual bactericidal-anti-sticking composite crosslinking coating as described in claim 1, characterized in that: The crosslinkable functional polymer is at least one of the following: acrylate polymers, polyurethane, polybutylene succinate, polybutylene terephthalate, polybutylene succinate-co-butylene terephthalate, polybutylene succinate-adipate, polycaprolactone, polypropylene carbonate, polyhydroxyalkanoic acid, polyhydroxybutyrate-hexanoate, poly3,4-hydroxybutyrate, cellulose ether, cellulose carbamate, cellulose nitrate, cellulose sulfonate, chitosan, hyaluronic acid, alginate, agarose, collagen, silk fibroin, silk protein, gelatin, polyphenols, polypeptides, or their derivatives.

6. The dual bactericidal-anti-sticky composite crosslinking coating as described in claim 2, characterized in that: The molecular weight of the crosslinkable release-type multifunctional branched polymer is 20,000-30,000.

7. The dual bactericidal-anti-sticky composite crosslinking coating as described in claim 3, characterized in that: The three-dimensional multi-active branched polymer compound is at least one of the following: modified hyperbranched / dendritic polyamide amine, modified hyperbranched polyethyleneimine, modified hyperbranched polyamino acid, and modified hyperbranched clustered peptide.

8. The method for preparing a dual bactericidal-anti-adhesive composite crosslinking coating as described in claim 1, characterized in that... Includes the following steps: 1) Preparation of crosslinkable multifunctional branched polymers using three-dimensional multi-active group branched polymer compounds; 2) The crosslinkable multifunctional branched polymer obtained in step 1) is combined with a release-type antibacterial active substance and then dialyzed to obtain a crosslinkable release-type multifunctional branched polymer. 3) Pre-crosslink the crosslinkable release multifunctional branched polymer obtained in step 2) with the crosslinkable functional polymer; 4) Prepare a functional coating from the pre-crosslinked solution obtained in step 3); 5) Post-process the sample from step 4) to obtain a dual sterilization-anti-adhesion composite cross-linking coating.

9. The method for preparing a dual bactericidal-anti-adhesive composite crosslinking coating as described in claim 8, characterized in that... The specific method in step 1) is as follows: a three-dimensional multi-active branched polymer compound is dissolved in a solvent, wherein the solvent is at least one of water, ethanol, methanol, and acetone. Compounds containing antibacterial and antiviral functional groups, compounds containing anti-adhesion functional groups, and functional active molecular groups are added respectively. After the reaction, the solvent is removed to obtain a crosslinkable multifunctional branched polymer.

10. The method for preparing a dual bactericidal-anti-adhesive composite crosslinking coating as described in claim 8, characterized in that... In step 2): the mass percentage of the releasing antibacterial active substance is 5-10%; the conditions for the composite reaction are: temperature 20-80℃, reaction time 6-24 hours, molecular weight cutoff of the dialysis bag 8000-15000, dialysis solution is one of distilled water and PBS buffer solution, and dialysis time 12-24 hours. The pre-crosslinking conditions in step 3) are: temperature 60-80℃, reaction time 12-24 hours.

11. The method for preparing a dual bactericidal-anti-adhesive composite crosslinking coating as described in claim 8, 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; The dipping conditions are: temperature 60-80℃, time 10-30 seconds; The spin coating conditions are: temperature 60-80℃, time 30-60 seconds; the spray coating conditions are: temperature 60-80℃, time 20-60 seconds.

12. The method for preparing a dual bactericidal-anti-adhesive composite crosslinking coating as described in claim 8, characterized in that... In step 5): the post-treatment includes natural air drying, vacuum drying, and solution phase inversion. The natural air drying conditions are: room temperature, time 6-24 hours; the vacuum drying conditions are: temperature 25-60℃, time 6-12 hours; and the solution phase inversion conditions are: temperature 15-37℃, time 15-30 minutes.

13. The method for preparing a dual bactericidal-anti-adhesive composite crosslinking coating as described in claim 10, characterized in that... The conditions for the complex reaction in step 2) are: temperature 30-70℃, reaction time 10-20 hours, molecular weight cutoff of dialysis bag 10000-12000, and dialysis time 15-20 hours.

14. The method for preparing a dual bactericidal-anti-sticking composite crosslinking coating as described in claim 11, 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 10μm-1mm.

15. The application of the dual bactericidal-anti-adhesive composite crosslinking coating as described in claim 1 in the preparation of antibacterial coatings, wherein the application includes the use as an antibacterial coating on the surfaces of various assets and goods in public places and homes.

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