阅读说明：本技术 一种含氟聚丙烯酸类共聚物抗菌复合材料的制备方法及所得产品和应用 (Preparation method of fluorine-containing polyacrylic acid copolymer antibacterial composite material, obtained product and application ) 是由 李文婷 李�学 于欢 任玉芳 李森 刘朋 于 2019-11-21 设计创作，主要内容包括：本发明公开了一种含氟聚丙烯酸类共聚物抗菌复合材料的制备方法及所得产品和应用,将无氟丙烯酸类单体和含氟丙烯酸酯单体聚合生成含氟聚丙烯酸类共聚物,然后将该含氟聚丙烯酸类共聚物进行适当交联,形成具有一定交联度的共聚物,最后将交联后的共聚物与抗菌剂复合,形成复合抗菌材料。本发明方法反应条件相对温和,操作简单,样品产率高,所得抗菌复合材料具有抗细菌粘附、杀菌、pH响应性以及荧光特性,可以制成薄膜或涂层用于产品表面,不仅可以阻止细菌、灰尘等的附着,还能将附着其上的细菌高效的杀除,防止死亡的细菌或者活细菌的粘附造成的杀菌效率降低,具有很好的抗污、抗菌作用,在医药、生物、卫生、食品等领域具有很好的应用前景。(The invention discloses a preparation method of a fluorine-containing polyacrylic acid copolymer antibacterial composite material, an obtained product and application thereof. The method disclosed by the invention is relatively mild in reaction conditions, simple to operate and high in sample yield, the obtained antibacterial composite material has antibacterial adhesion, sterilization, pH responsiveness and fluorescence characteristics, can be prepared into a film or a coating for the surface of a product, can prevent the adhesion of bacteria, dust and the like, can efficiently kill the bacteria adhered to the film or the coating, can prevent the sterilization efficiency from being reduced due to the adhesion of dead bacteria or live bacteria, has good anti-fouling and antibacterial effects, and has a good application prospect in the fields of medicines, biology, sanitation, food and the like.)

1. A preparation method of a fluorine-containing polyacrylic acid copolymer antibacterial composite material is characterized by comprising the following steps:

(1) polymerizing a fluorine-free acrylic monomer and a fluorine-containing acrylate monomer to obtain a fluorine-containing polyacrylic copolymer;

(2) dissolving the fluorine-containing polyacrylic acid copolymer obtained in the step (1) in a solvent to prepare a solution, and then adding a cross-linking agent into the solution to carry out a cross-linking reaction to obtain a cross-linked fluorine-containing polyacrylic acid copolymer;

(3) and (3) compounding the crosslinked fluorine-containing polyacrylic acid copolymer obtained in the step (2) with an antibacterial agent to obtain the fluorine-containing polyacrylic acid copolymer antibacterial composite material.

2. The method of claim 1, wherein: the fluorine-containing acrylate is1H,1H,7HPerfluoroheptyl methacrylate, dodecafluoroheptyl methacrylate, pentafluorophenyl methacrylate, hexafluorobutyl methacrylate, perfluoroheptyl methacrylate, perfluorohexyl methacrylate, perfluoroheptyl methacrylate,1H， 1H，2H，2Hone or more of heptadecafluorodecyl acrylate, trifluoroethyl methacrylate and perfluorooctyl ethyl methacrylate, preferably 1H, 1H, 2H, 2H-heptadecafluorodecyl acrylate, perfluorooctyl ethyl methacrylate and1H,1H, 7H-one or two of perfluoroheptyl methacrylate; the fluorine-free acrylic monomer includes acrylic acid or methacrylic acid.

3. The method of claim 1, wherein: the crosslinking agent is an aziridine crosslinking agent, a polyisocyanate crosslinking agent, an epoxy silane crosslinking agent or a polycarbodiimide crosslinking agent, and is preferably one or two of the aziridine crosslinking agent and the epoxy silane crosslinking agent.

4. The method of claim 1, wherein: the antibacterial agent is guanidine, inorganic nano particles, imidazole, quaternary ammonium salts or antibiotics with interaction with carboxyl; preferably, the guanidine antibacterial agent is polyhexamethylene biguanide hydrochloride or polyhexamethylene monoguanidine; preferably, the inorganic nanoparticles are nano silver, nano zinc oxide or nano titanium oxide; preferably, the imidazole antibacterial agent is metronidazole or fluconazole; preferably, the antibiotic interacting with the carboxyl is vancomycin, gentamicin sulfate, chloramphenicol or erythromycin; more preferably, the antibacterial agent is polyhexamethylene biguanide hydrochloride, polyhexamethylene monoguanidine or inorganic nanoparticles.

5. The method of claim 1, wherein: in the step (1), the molar ratio of the fluorine-containing acrylate monomer to the fluorine-free acrylic monomer is 1:10-1:90, preferably 1:30-1: 75; preferably, in step (1), the polymerization reaction is carried out in the presence of an initiator, and the molar ratio of the fluorine-free acrylic monomer to the initiator is 180-220: 1.

6. The method of claim 1, 2 or 5, wherein: in the step (1), the polymerization method is free radical polymerization, atom transfer radical polymerization, RAFT polymerization or anion polymerization; preferably, the polymerization temperature is 50-80 ℃ and the polymerization time is 4-24 h.

7. The method according to claim 1 or 3, wherein: in the step (2), the molar ratio of the cross-linking agent to the carboxyl in the fluorine-free acrylic monomer is 0.03-0.6: 1, preferably 0.05-0.3: 1.

8. The method according to claim 1 or 4, wherein: in the step (3), the molar ratio of the antibacterial agent to the carboxyl in the fluorine-free acrylic monomer is 0.5-20:1, preferably 5-15: 1; preferably, in the step (3), the crosslinked fluorine-containing polyacrylic acid copolymer and the antibacterial agent are compounded by means of impregnation or mixing.

9. The fluorine-containing polyacrylic acid copolymer antibacterial composite material prepared by the preparation method of the fluorine-containing polyacrylic acid copolymer antibacterial composite material according to any one of claims 1 to 8 and application of the fluorine-containing polyacrylic acid copolymer antibacterial composite material in the fields of medicine, biology, health and food.

10. A product characterized by: the surface is covered with an antibacterial coating, and the effective component of the antibacterial coating comprises the fluorine-containing polyacrylic acid copolymer antibacterial composite material of claim 9.

Technical Field

The invention relates to a preparation method of a fluorine-containing polyacrylic acid copolymer antibacterial composite material, an obtained product and application, and belongs to the technical field of high-molecular antibacterial materials.

Background

Bacterial infections, which involve many critical areas of medical health, food safety, biomedical devices, etc., seriously threaten human health and even cause death, have become the biggest public health problem in the world, and are reported in millions every year. Particularly in hospitals, infections are rapidly spread in the medical facilities through various surface-caregiver-patient contact cycles and are difficult to prevent and eradicate, and it is estimated that hospitalized patients are suffering from nosocomial infections, nearly half of which are associated with bacterial contamination of various surfaces. It has been shown that once bacteria adhere to the surface of the material, as the number of cells increases, a biofilm of bacteria is formed which is difficult to remove, microbial cells survive even under harsh conditions, and the tolerance of the bacteria in the biofilm to antibiotics and other antiseptics is improved by more than 1000-fold compared to planktonic bacteria. Therefore, in the research of antibacterial agents, it is important to prevent early bacterial adhesion, prevent the formation of biofilm, kill planktonic bacteria by bactericides before bacterial adhesion, or inhibit bacterial adhesion by surface modification, which has been a hot point of research internationally. In addition, due to abuse of antibiotics, drug-resistant genes diffuse among different bacteria, so that the drug resistance of various pathogenic bacteria is continuously enhanced, and the existing antibacterial materials are difficult to cope with the evolving pathogenic bacteria. In order to deal with disease transmission caused by pathogenic bacteria, the material which can inhibit bacterial adhesion and biofilm formation and has sterilization performance is developed, and is the aim of continuous pursuit.

Due to the unique surface properties of the fluorine-containing polymer, such as low surface energy, low Young modulus and good self-cleaning property, fluorine is introduced into a molecular structure, so that a material with excellent anti-adhesion performance and antibacterial performance is obtained, and the research and development directions of the current antibacterial materials are also provided. However, due to the hydrophobic and oleophobic characteristics of the fluorine-containing polymer, the fluorine-containing polymer is not easy to disperse in a solvent when being used as an antibacterial material alone, so that the application difficulty of the fluorine-containing polymer is increased; and the surface energy of the fluorine-containing polymer is low, the interaction with a substrate is not easy, and a stable coating cannot be obtained.

Disclosure of Invention

The invention aims to provide a preparation method of a fluorine-containing polyacrylic acid copolymer antibacterial composite material, which is characterized in that a hydrophobic fluorine-containing acrylic acid monomer and a hydrophilic fluorine-free acrylic acid monomer are copolymerized, hydrophilic and hydrophobic monomers are linked, and a further composite antibacterial agent is obtained after slight crosslinking.

The invention also provides the fluorine-containing polyacrylic acid copolymer antibacterial composite material prepared by the method, and the antibacterial composite material can resist bacterial adhesion, inhibit bacterial adhesion and biofilm formation, has good bactericidal effect, and has synergistic effect and excellent antifouling and antibacterial properties.

The invention also provides the application of the fluorine-containing polyacrylic acid copolymer antibacterial composite material in the fields of medical treatment, biology, health, food and the like, the material can be used as an effective component of an antibacterial coating and is arranged on the surfaces of various medical, biological, health and food products, so that the material can play a good antifouling and antibacterial role, and the antibacterial performance and the antibacterial durability of the product are improved.

The specific technical scheme of the invention is as follows:

a preparation method of a fluorine-containing polyacrylic acid copolymer antibacterial composite material comprises the following steps:

(1) polymerizing a fluorine-free acrylic monomer and a fluorine-containing acrylate monomer to obtain a fluorine-containing polyacrylic copolymer;

(2) dissolving the fluorine-containing polyacrylic acid copolymer obtained in the step (1) in a good solvent to prepare a solution, and then adding a cross-linking agent into the solution to carry out a cross-linking reaction to obtain a cross-linked fluorine-containing polyacrylic acid copolymer;

(3) and (3) compounding the cross-linked fluorine-containing polyacrylic acid copolymer obtained in the step (2) with an antibacterial agent to obtain the fluorine-containing polyacrylic acid copolymer antibacterial composite material (antibacterial composite material for short, the same below).

Further, in the step (1), the fluorine-free acrylic monomer and the fluorine-containing acrylate monomer are polymerized to obtain a copolymer of the fluorine-free acrylic compound and the fluorine-containing acrylate, so that a certain amount of fluorocarbon side chains are suspended from the side chains of the copolymer. The fluorine-containing acrylate is1H,1H,7HPerfluoroheptyl methacrylate, dodecafluoroheptyl methacrylate, pentafluorophenyl methacrylate, hexafluorobutyl methacrylate, perfluoroheptyl methacrylate, perfluorohexyl methacrylate, perfluoroheptyl methacrylate,1H，1H，2H，2Hone or more fluorine-containing acrylate monomers such as heptadecafluorodecyl acrylate, trifluoroethyl methacrylate and perfluorooctyl ethyl methacrylate. The monomers can be prepared by the existing method. When the fluorocarbon side chain is linear and has a length of more than 8, it is appropriate under other conditionsUnder the condition, the fluorocarbon side chains can be regularly arranged, when the fluorine-containing polyacrylic copolymer antibacterial composite material is prepared into a film, the surface energy of the film can be effectively reduced, and the fluorocarbon side chains cannot play a role in reducing the surface energy of the film when being shorter. Preferably, the fluoroacrylate is1H，1H， 2H，2H-heptadecafluorodecyl acrylate, perfluorooctyl ethyl methacrylate and1H,1H,7H-perfluoroheptyl methacrylate.

Further, in the step (1), the fluorine-free acrylic monomer includes carboxylic acid-containing acrylic monomers such as acrylic acid and methacrylic acid.

Further, in the step (1), the molar ratio of the fluorine-containing acrylate monomer to the fluorine-free acrylic monomer is 1:10 to 1:90, preferably 1:30 to 1: 75. When the molar ratio of the fluorine-containing acrylate to the fluorine-free acrylic monomer is more than 1:10, the hydrophilicity of the obtained copolymer is reduced, the copolymer cannot be uniformly dispersed in water, other organic solvents are needed, the environment is not protected, and the fluorescence intensity of the synthesized copolymer is weakened, so that the macroscopic detection is not facilitated. When the molar ratio of the fluorine-containing acrylate to the fluorine-free acrylic monomer is less than 1:90, the fluorine content of the polymer is too low to effectively reduce the surface energy of the antibacterial composite material film.

Further, in the step (1), the polymerization of the fluorine-containing acrylate monomer and the fluorine-free acrylic monomer may be performed by various polymerization methods disclosed in the prior art, such as radical polymerization, atom transfer radical polymerization, RAFT polymerization, anion polymerization, etc., and those skilled in the art may select a suitable polymerization method and process conditions according to the methods disclosed in the prior art.

Further, the molecular weight of the copolymer is controlled by the amount of the initiator. The molar ratio of the fluorine-free acrylic monomer to the initiator is 180-220: 1. The initiator may be any of the various initiators commonly used in polymer chemistry reported in the art, such as azobisisobutyronitrile, dibenzoyl peroxide, and the like.

Preferably, in the step (1), the polymerization temperature is 50-80 ℃ and the polymerization time is 4-24 h.

Further, in the step (1), the polymerization reaction is carried out in an organic solvent, which may be tetrahydrofuran or the like.

Further, in the step (2), the crosslinking agent is one or more of an aziridine crosslinking agent, a polyisocyanate crosslinking agent, an epoxy silane crosslinking agent and a polycarbodiimide crosslinking agent. The aziridine crosslinking agent and the carboxyl have high reaction speed and obvious effect at room temperature, the antibacterial composite material obtained by the epoxy silane crosslinking agent has strong interaction with a substrate when being prepared into a film or a coating, and the coating is resistant to organic solvents, acids and alkalis. Thus, the crosslinking agent is preferably one or both of an aziridine crosslinking agent and an epoxy silane crosslinking agent.

Further, in the step (2), the molar ratio of the crosslinking agent to the carboxyl group in the fluorine-free acrylic monomer in the step (1) is from 0.03 to 0.6: 1. when the dosage of the cross-linking agent is too small, the cross-linking degree of the copolymer is too low, and the water resistance of the film formed by the finally obtained antibacterial composite material is poor; when the amount of the cross-linking agent is excessively large, the stability of the finally obtained antibacterial composite material in water is poor. Preferably, the molar ratio of the crosslinking agent to the carboxyl groups in the fluorine-free acrylic monomer is from 0.05 to 0.3: 1.

Further, in the step (2), the temperature for crosslinking may be appropriately selected according to the kind of the crosslinking agent.

Further, in the step (2), the crosslinking reaction is preferably carried out at room temperature.

In the step (2), the good solvent is a solvent having a high solubility in the fluorinated polyacrylic acid-based copolymer, and is, for example, water or another organic solvent, preferably water. The dosage of the good solvent can meet the requirement of normal crosslinking reaction without special requirement.

Further, in the step (2), the fluorine-containing polyacrylic acid copolymer is appropriately crosslinked. The fluorine-containing polyacrylic acid copolymer has excellent anti-adhesion performance due to unique surface properties, such as low surface energy, low Young modulus and good self-cleaning property. In addition, the stability of the copolymer can be improved by crosslinking the copolymer to a certain degree. The adhesion resistance of the copolymer can reduce the adsorption of bacteria, prevent the bacteria from forming a large amount of biological films and improve the antibacterial effect of the antibacterial agent.

Further, in the step (3), the antibacterial agent is a substance having bactericidal, antibacterial and bacteriostatic effects and capable of interacting with carboxyl. The interaction with the carboxyl group means that the group or atom in the substance has electrostatic interaction and hydrogen bond interaction with the carboxyl group.

Furthermore, the antibacterial agent is one of guanidine, inorganic nano particles, imidazole, quaternary ammonium salts, antibiotics with interaction with carboxyl, and the like.

Further, the guanidine antibacterial agent may be polyhexamethylene biguanide hydrochloride, polyhexamethylene monoguanidine, or the like. The inorganic nano particles can be nano silver, nano zinc oxide, nano titanium oxide and the like. The imidazole antibacterial agent can be metronidazole, fluconazole and the like. The antibiotic interacting with carboxyl can be vancomycin, gentamicin sulfate, chloramphenicol, erythromycin, etc.

Furthermore, the interaction between the polyhexamethylene biguanide hydrochloride, the polyhexamethylene monoguanidine and the inorganic nano particles and the carboxylic acid is strong, the cytotoxicity is low, and the drug resistance of bacteria can not be caused. Accordingly, the antibacterial agent is preferably polyhexamethylene biguanide hydrochloride, polyhexamethylene monoguanidine or inorganic nanoparticles.

Further, in the step (3), the molar ratio of the antibacterial agent to the carboxyl group in the fluorine-free acrylic acid compound is 0.5 to 20:1, preferably 5 to 15: 1. When the content of the antibacterial agent is too large, the antibacterial adhesion effect of the finally obtained antibacterial composite material is poor when the antibacterial agent is made into a film or a coating, and when the content of the antibacterial agent is too small, the antibacterial effect of the finally obtained antibacterial composite material is reduced when the antibacterial agent is made into a film or a coating.

Further, in the step (3), the crosslinked fluorinated polyacrylic acid copolymer and the antibacterial agent can be effectively compounded in any feasible manner reported in the prior art, and the compounding of the crosslinked fluorinated polyacrylic acid copolymer and the antibacterial agent is realized through the interaction (electrostatic interaction and hydrogen bonding) of carboxyl groups in the copolymer and the antibacterial agent. For example, the composite may be formed by impregnation, mixing, etc. to form the final antimicrobial composite. Because the antibacterial agent contains a group which can interact with carboxyl in the fluorine-containing polyacrylic acid copolymer, the antibacterial agent can be well combined with the cross-linked fluorine-containing polyacrylic acid copolymer and is not easy to fall off.

Further, in a specific embodiment of the present invention, a compounding method of a crosslinked fluorine-containing polyacrylic acid copolymer and an antibacterial agent is provided, specifically: and (3) mixing the water solution of the cross-linked fluorine-containing polyacrylic acid copolymer with the mixed solution of polyhexamethylene biguanide hydrochloride and ammonia water overnight to realize the compounding of the cross-linked fluorine-containing polyacrylic acid copolymer and the antibacterial agent. After complexing, the uncomplexed antimicrobial agent is removed, and excess antimicrobial agent can be removed by dialysis or precipitation. The finally formed antibacterial composite material can be in the form of aqueous solution, and further can be made into a film or coated on the surface of a substrate to form a coating.

The fluorine-containing polyacrylic acid copolymer antibacterial composite material obtained by the invention has the characteristics of fluorescence, adhesion resistance and sterilization, and pH responsiveness, and the product is also in the protection scope of the invention.

The fluorine-containing polyacrylic acid copolymer antibacterial composite material has good application prospects in the fields of medicine, biology, sanitation, food and the like, can be used as an antibacterial component independently or in combination with other components to be prepared into an antibacterial film or an antibacterial coating, and can be used on the surfaces of various products with different functions to play antibacterial and bacteriostatic roles and reduce the propagation and infection of bacteria.

The invention also provides a product, wherein the surface of the product is coated with an antibacterial coating, and the effective component of the antibacterial coating comprises the fluorine-containing polyacrylic acid copolymer antibacterial composite material.

The invention polymerizes a fluorine-free acrylic monomer and a fluorine-containing acrylate monomer to generate a fluorine-containing polyacrylic copolymer, then properly crosslinks the fluorine-containing polyacrylic copolymer to form a copolymer with a certain crosslinking degree, and finally compounds the crosslinked copolymer with an antibacterial agent to form the composite antibacterial material. The method has the advantages of relatively mild reaction conditions, simple operation, high sample yield and large-scale production. The antibacterial composite material has the characteristics of antibacterial adhesion, sterilization, pH responsiveness and fluorescence, can be made into a film or a coating for the surface of a product, can prevent the adhesion of bacteria, dust and the like, can efficiently kill the bacteria adhered to the film or the coating, can prevent the sterilization efficiency reduction caused by the adhesion of dead bacteria or live bacteria, has good antifouling and antibacterial effects, and has better application prospects in the fields of medicine, biology, sanitation, food and the like.

Drawings

FIG. 1 is an infrared image of the fluorinated polyacrylic copolymer complex polyhexamethylene biguanide hydrochloride prepared in example 1.

FIG. 2 is a fluorescence spectrum of the fluorinated polyacrylic copolymer complex polyhexamethylene biguanide hydrochloride prepared in example 1.

FIG. 3 is an SEM image (magnification 2000) of the anti-bacterial adhesion of a silicon wafer (a) and a fluorine-containing polyacrylic copolymer composite polyhexamethylene biguanide hydrochloride film (b) prepared in example 1.

FIG. 4 is a photograph of a silicon wafer (a) and a fluorine-containing polyacrylic copolymer composite polyhexamethylene biguanide hydrochloride film (b) prepared in example 1 as a blanket against bacterial adhesion.

FIG. 5 is a statistical chart of bacteria adhered to the surfaces of silicon wafers in an anti-adhesion experiment and the fluorine-containing polyacrylic acid copolymer composite polyhexamethylene biguanide hydrochloride film prepared in example 1.

FIG. 6 is an SEM image (magnification 2000) of a sterilization experiment of a silicon wafer (a) and a fluorine-containing polyacrylic acid copolymer composite polyhexamethylene biguanide hydrochloride film (b) prepared in example 1.

FIG. 7 is a photograph of a silicon wafer (a) and a fluorine-containing polyacrylic copolymer composite polyhexamethylene biguanide hydrochloride film (b) prepared in example 1 on a plate for a sterilization test.

FIG. 8 shows the statistics of viable bacteria on the surface of the silicon wafer in the sterilization experiment and the fluorine-containing polyacrylic acid copolymer composite polyhexamethylene biguanide hydrochloride film prepared in example 1.

Detailed Description

The present invention will be described in further detail with reference to specific examples. In the following examples, acrylic acid, fluorine-containing acrylate, a crosslinking agent, and an antibacterial agent were all commercially available.

In the following examples, the following methods were used for the anti-adhesion, anti-bacterial and cytotoxicity tests of the antibacterial composite material:

and dripping the water solution of the prepared fluorine-containing polyacrylic acid copolymer antibacterial composite material on a silicon wafer with the thickness of 1 multiplied by 1cm, and performing antibacterial adhesion and sterilization experiments after drying.

Anti-adhesion test: placing a silicon wafer into a container containing 10⁸And (3) culturing the staphylococcus aureus in a PBS (phosphate buffered saline) solution of CFU/mL for 4h, and taking a pure silicon wafer as a negative control. After culturing at 37 ℃ for 4h, slightly washing each silicon wafer by PBS solution for 3 times, adding 2mL PBS to dilute in sequence, taking 200 μ L of the solution to directly plate, culturing at 37 ℃ for 24h, observing the growth condition of surface bacteria and counting the bacterial adhesion quantity, or simultaneously fixing by 4% paraformaldehyde for 30min, washing by sterile water for 3 times, vacuum drying, and observing the quantity and the shape of the surface bacteria by SEM.

And (3) sterilization experiment: placing a silicon wafer into a container containing 10⁶Culturing in LB solution of CFU/mL staphylococcus aureus for 24h, and taking pure silicon chip as negative control. After culturing at 37 ℃ for 24h, slightly washing each silicon wafer by PBS solution for 3 times, adding 2mL PBS to dilute in sequence, taking 200 μ L of the solution to directly pave, after culturing at 37 ℃ for 24h, observing the growth condition of surface bacteria and counting the number of viable bacteria, or after fixing with 4% paraformaldehyde for 30min, washing with sterile water for 3 times, vacuum drying, and observing the number and the shape of the surface bacteria by SEM.

Cytotoxicity experiments: culturing cells in 10% fetal calf serum and 1% penicillin streptomycin culture solution for 24h, adding 0.9% NaCl extract solution for co-culturing for 24h, adding 10 μ L CCK-8 solution, culturing for 2h, and measuring OD₄₅₀Simultaneously, the sample solution is not added as a comparison sample, and the OD of the comparison sample₄₅₀Comparing and calculating the cell survival rate, the cell survival rate of more than 90 percent indicates that the material is less toxic, and the survival rate of less than 90 percent indicates that the material is more toxic.