Antibacterial and anti-adhesion functional emulsion as well as preparation method and application thereof

Abstract

The invention belongs to the field of biomedical materials, and relates to preparation and application of an antibacterial and anti-adhesion functional emulsion. The emulsion is prepared by taking an antibacterial functional monomer and an anti-adhesion functional monomer as core raw materials, adding a hydrophobic unit, a hydrophilic unit, a flatting agent and an adhesion promoter in proportion, and performing polymerization crosslinking under the combined action of a multi-component acrylate functional crosslinking agent, an internal crosslinking agent and an initiator. The emulsion not only can form an antibacterial and anti-adhesion polymer brush on the surface of a material, but also can form an anti-adhesion annular structure of a wire layer and a surface layer, and plays an all-around anti-adhesion role. A medical instrument product containing the emulsion can achieve the antibacterial effect of more than 99% on staphylococcus aureus, escherichia coli and candida albicans, and the coating falling grade is 0 grade; the contact angle is 42-53 degrees, the number of platelets is 81.3%-97.6%, and an excellent blood adhesion resisting effect is achieved; after being eluted in normal saline for 30 days, the anti-bacterial and anti-adhesion effects can still be good, and cytotoxicity and hemolysis are avoided.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedical materials and relates to an antibacterial and anti-adhesion functional emulsion and a preparation method and application thereof. Background Art

[0002] Medium- and long-term implantable medical devices are usually made of polymer materials and can be used to assist in the treatment of a variety of diseases. They are mainly used in critical care departments such as oncology, anesthesiology, and ICU. However, as the implantation time of medical devices increases, the intrinsic hydrophobicity of the material induces significant nonspecific protein adsorption under physiological conditions, which may lead to many potential immune responses, such as cell adhesion, platelet adhesion, blood coagulation, and thrombosis. At the same time, it triggers a series of events involving biological contamination processes, leading to inflammation, local infection, and rejection of implanted materials, which in turn leads to bacteremia, sepsis, and even sepsis, with the risk of death in severe cases.

[0003] Biomaterial-centered infections involve the adhesion and subsequent colonization of bacteria on the surface of biomaterials. Nosocomial infections caused by pathogenic bacteria adhering to the surface of medical devices have become one of the biggest hidden dangers to patient health worldwide, seriously endangering social public health security. Microbial contamination causes bacterial and fungal biofilms to form on the surface of implanted medical devices. Biofilms are complex aggregations of microorganisms that have multiple drug resistance and immune escape capabilities compared to planktonic bacteria. Therefore, they are highly pathogenic and difficult to cure, and can also cause great pain and economic burden to patients. Preventing bacterial adhesion or at least significantly reducing the number of live bacteria, while making the surface of biomaterials have antibacterial functions, is an effective way to minimize bacterial infections. Therefore, it is of great application value to prepare coatings with antibacterial and anti-adhesion functions on the surface of implantable medical devices to reduce the risk of infection and coagulation.

[0004] At present, there are many types of antibacterial and anti-adhesion coatings in China. Chinese patent application CN106075577A proposes an antibacterial coating based on organic guanidine salts and polyethylene glycol. By synthesizing tosyl polyethylene glycol monoallyl ether and combining it with guanidine salts, a functionalized diblock copolymer is obtained. The diblock copolymer is then allyl functionalized, and the polymer is obtained through repeated sedimentation, dissolution and purification processes. The invention uses argon plasma technology for coating pretreatment, and acts on polydimethylsiloxane materials to have good antibacterial and anti-adhesion properties. However, the invention does not verify the firmness and elution resistance of the coating, and it is currently impossible to determine the timeliness of the antibacterial and anti-adhesion functions.

[0005] Chinese patent application CN104327663A discloses a polymer coating with dual antifouling and antibacterial effects, which is prepared by quaternizing a copolymer having a zwitterionic structure, methoxypolyethylene glycol-b-polyethyl methacrylate dimethylsulfopropyl betaine-b-polydimethylaminoethyl methacrylate, and 3-chloropropyltriethoxysilane. Before use, the substrate needs to be placed in a high-concentration hydrogen peroxide and concentrated sulfuric acid mixture for treatment and activation. It is mainly used in ships, marine engineering machinery and sewage treatment equipment on glass and metal surfaces. There are still major problems with the production efficiency and safety of the pretreatment process, and it is not suitable for polymer material products. Chinese patent CN102307955B provides a grafted composite with non-fouling, antibacterial and anti-thrombotic functions formed by a zwitterionic polymer. It is grafted to the surface of the substrate to resist the attachment of biological materials, and has good biocompatibility and no cytotoxicity. However, the construction process is relatively complicated. The substrate needs to be repeatedly immersed in the primer solution four times, and then undergo a grafting polymerization reaction after a long period of drying. In addition, the substrates to which the grafting process can be applied are relatively limited.

[0006] Chinese patent CN104710644B proposes a double-layer structure brush that uses ultraviolet light-induced transfer termination polymerization to construct an antibacterial anti-adhesion brush bottom layer and an antibacterial brush upper layer. The bacterial infection process is usually adhesion first and then growth. This structure easily leads to bacterial adhesion and accumulation of dead bacteria, which in turn affects the surface antibacterial performance. CN111995788B discloses a method for preparing a polymer brush with bacterial responsiveness, which uses ultraviolet light-induced active polymerization to construct a double-layer surface, so that the polymer brush has a double-layer structure with an antibacterial adhesion layer on the top and an antibacterial brush layer on the bottom, which not only gives the material surface antibacterial adhesion properties, but also has excellent blood compatibility and cell compatibility. However, the response surface needs to be affected by the physiological pH value to take effect, and the variability and complexity of the actual clinical application environment also increase the risk of uncontrollable antibacterial function.

[0007] Chinese patent CN109529128B discloses an anti-infection coating and its preparation method. First, the surface of the medical polymer material is coated with a photoinitiator; then it is placed in a mixed solution including anti-adhesion monomers, polymerization monomers and polyethylene glycol diacrylate, and a material with a gel coating is obtained through a UV cross-linking reaction; finally, the material is placed in a coupling reagent for an overnight antibiotic loading reaction to obtain an antibacterial coating. The coating achieves the antibacterial purpose by means of antibiotic dissolution. As time goes by, the antibacterial performance gradually decreases, and long-term contact between antibiotics and the body will reduce the sensitivity of microorganisms to drugs, improve their tolerance and resistance, and drug-resistant microorganisms are prone to invade other parts to cause complications.

[0008] Chinese patent CN107759104B discloses a quaternary ammonium polymer brush antibacterial material based on Si-ATRP method and its preparation method, firstly modifying the surface of the material with active groups, then polymerizing with acrylamide monomers to obtain a polymer brush base material; then performing amide degradation reaction and quaternization reaction to obtain a quaternary ammonium polymer brush antibacterial material. The method of this invention is simple, low in cost, and easy to industrialize, but has high selectivity for substrates, and the safety of this method has not been confirmed.

[0009] At present, the existing antibacterial and anti-adhesion dual-functional combined surfaces are mostly functional polymer brush structures, and the timeliness and scope of anti-adhesion are limited. At the same time, functional emulsions also have problems in safety, drug resistance and limited usage scenarios. There is no ideal functional coating material with antibacterial and anti-adhesion properties and good biocompatibility to provide medical devices with safe implantation and long-lasting antibacterial and anti-adhesion properties. Summary of the invention

[0010] Based on this, the purpose of the present invention is to provide an antibacterial and anti-adhesion functional emulsion, which can be applied to a variety of medical device products, not only has excellent antibacterial and anti-adhesion properties, but also has the characteristics of long-lasting stability and non-cytotoxicity.

[0011] The invention also provides a method for preparing the antibacterial and anti-adhesion functional emulsion and application of the emulsion in medical device products.

[0012] To achieve the above object, the present invention adopts the following technical solutions: The invention provides an antibacterial and anti-adhesion functional emulsion, which is prepared by polymerization and cross-linking with antibacterial functional monomers and anti-adhesion functional monomers as core raw materials, deionized water as solvent, and hydrophobic units, hydrophilic units, leveling agents and adhesion promoters added in proportion, under the joint action of a polyacrylate functional cross-linking agent, an internal cross-linking agent and an initiator.

[0013] Furthermore, each raw material component includes the following components in parts by weight: 10-15 parts of antibacterial functional monomer, 12-18 parts of anti-adhesion functional monomer, 25-40 parts of hydrophobic unit, 6-10 parts of hydrophilic unit, 0.1-1.0 parts of leveling agent, 0.5-1.5 parts of adhesion promoter, 1-3 parts of polyacrylate functional crosslinking agent, 0.5-1.5 parts of internal crosslinking agent, 0.3-0.9 parts of initiator, and 260-400 parts of deionized water.

[0014] Furthermore, the antibacterial functional monomer includes polyhexamethylene biguanide methacrylic acid (PHMB-MA) obtained by grafting modification of polyhexamethylene biguanide hydrochloride, and the polyhexamethylene biguanide hydrochloride with a molecular weight of 2000-3000 Da is first neutralized with a strong base to obtain a polymerized biguanide, and then methacryloyl chloride is added at a molar ratio of 1:1-1.5 at 37±2°C to react with the polymerized biguanide; then, unreacted acryloyl chloride is extracted from the aqueous phase with tetrahydrofuran, and then unreacted substances and tetrahydrofuran are extracted from the aqueous phase with petroleum ether, and finally the aqueous phase is subjected to rotary evaporation and freeze-drying for separation and purification to obtain the obtained product.

[0015] Furthermore, the polyacrylate functional crosslinker includes a bidentate polyethylene glycol acrylate linear functional crosslinker and a tetradentate polyethylene glycol acrylate star-shaped functional crosslinker, which is prepared by dissolving polyethylene glycol diamine or four-arm polyethylene glycol tetraamine and methacrylate-N-succinimide in dimethylformamide, reacting for 8-12 hours at room temperature under nitrogen protection under the catalysis of N,N-diisopropylethylamine to obtain a crude product, then placing the crude product in a dialysis bag with a cutoff of 2000Da for 48-72 hours, and freeze-drying and purification to obtain a bidentate polyethylene glycol acrylate linear functional crosslinker or a tetradentate polyethylene glycol acrylate star-shaped functional crosslinker.

[0016] Furthermore, the molar ratio of the polyethylene glycol diamine to the methacrylate-N-succinimide ester is 1:2-3; the molar ratio of the four-arm polyethylene glycol tetraamine to the methacrylate-N-succinimide ester is 1:4-5; the molecular weight of the polyethylene glycol diamine can be selected to be 5000Da, and the molecular weight of the four-arm polyethylene glycol tetraamine can be selected to be 10000Da.

[0017] Furthermore, the anti-adhesion functional monomer includes a polyethylene glycol methacrylate monomer with a molecular weight of 500-3000 Da; the polyethylene glycol methacrylate monomer includes any one of polyethylene glycol methacrylate, polyethylene glycol methyl ether methacrylate and polyethylene glycol ethyl ether methacrylate.

[0018] Furthermore, the hydrophobic unit is composed of an alkyl acrylate monomer and a tertiary carbon group-containing functional ester monomer; the alkyl acrylate monomer includes any one of methyl methacrylate, ethyl methacrylate, butyl methacrylate and lauryl methacrylate, and the tertiary carbon group-containing functional ester monomer includes any one of tertiary carbon glyceryl acrylate, tertiary carbon glyceryl methacrylate, tertiary carbonic acid maleate and tertiary carbonic acid epoxy acrylate.

[0019] Furthermore, the internal crosslinking agent includes any one of N,N-methylenebisacrylamide, N,N-dihydroxyethylbisacrylamide and N,N-vinylbisacrylamide; the leveling agent is 2,4,7,9-tetramethyl-5-decyne-4,7-diol polyoxyethylene ether; the adhesion promoter includes any one or more of tetrahydrofurfuryl acrylate, 2-tetrahydrofuran methacrylate and 1,6-hexanediol diacrylate; the initiator includes any one of ammonium persulfate, potassium persulfate and sodium persulfate; the hydrophilic unit includes any one of acrylic acid, methacrylic acid, hydroxyethyl acrylate, hydroxyethyl methacrylate, hydroxypropyl methacrylate and glycidyl methacrylate.

[0020] The present invention also provides a method for preparing an antibacterial and anti-adhesion functional emulsion, comprising the following steps: S1, adding a hydrophilic unit, a hydrophobic unit and deionized water into a reaction container, and stirring at a stirring rate of 300±20rpm / min for 20-30min to obtain a solution A; S2, adding antibacterial functional monomer, anti-adhesion functional monomer, polyacrylate functional crosslinking agent and internal crosslinking agent to solution A, stirring and gradually heating to 70-90° C. to obtain solution B; S3, adding part of the initiator to solution B, reacting for 3-6 hours under nitrogen protection, adding the remaining amount of initiator, and continuing the reaction for 1-2 hours to obtain solution C; S4, placing solution C in a dialysis bag for 48-72 hours, with a molecular weight cutoff of 3000-4000Da, removing excess water, adding a leveling agent and an adhesion promoter, and mixing well to obtain an antibacterial and anti-adhesion functional emulsion.

[0021] Finally, the present invention also provides an application of an antibacterial anti-adhesion functional emulsion in an antibacterial anti-adhesion medical product, wherein the antibacterial anti-adhesion functional emulsion described in any one of claims 1 to 8 is applied to the surface of the medical product by dipping, brushing, roller coating or spraying, and cured at 50-70°C for 6-8h to obtain the obtained product. Wherein: the medical product includes any one of a central venous catheter, a peripherally inserted central venous catheter, a hemodialysis catheter, a urinary catheter and an indwelling needle. The medical product can achieve an antibacterial effect of >99% against Staphylococcus aureus, Escherichia coli and Candida albicans, and the coating shedding grade is 0; the contact angle is 42-53°, the platelet count is 81.3%-97.6%, and it has an excellent anti-blood adhesion effect; after elution in physiological saline for 30 days, it can still achieve a good antibacterial and anti-adhesion effect, without cytotoxicity and hemolysis.

[0022] The beneficial effects of the present invention are: 1. Compared with the prior art, the present invention constructs the main chain of the functional emulsion by compounding the hydrophilic unit and the hydrophobic unit system, and then polymerizes the modified polyhexamethylene biguanide methacrylate (PHMB-MA) antibacterial functional monomer and the polyethylene glycol methacrylate anti-adhesion functional monomer with the main chain to construct a polymer brush structure to exert antibacterial and anti-adhesion effects. Based on the polymer brush structure, all end groups of the homemade polyacrylate functional crosslinker can be polymerized with the main chain to form a "line layer" and a "surface layer" ring structure, which can show a full range of anti-adhesion properties, not only anti-bacterial adhesion properties, but also give the surface excellent blood compatibility and cell compatibility.

[0023] 2. The present invention modifies polyethylene glycol diamine and four-arm polyethylene glycol tetraamine by methacrylate-N-succinimidyl ester, introduces acrylate groups, generates bidentate polyethylene glycol acrylate linear functional crosslinkers and tetradentate polyethylene glycol acrylate star functional crosslinkers, further improves the crosslinking density, and covers the polymer surface to form a high-density hydration layer with high stability and steric hindrance effect. The hyperbranched structure formed by the crosslinking network increases the contact area with bacteria and has better stability and anti-adhesion.

[0024] 3. The present invention prepares modified polymeric biguanide functional monomers, which have better designability and controllability, and can be fixed on the surface of medical polymer materials without losing biological activity, and can kill microorganisms without releasing biocides, which can prevent bacteria from developing drug resistance. Modified polymeric biguanide can more efficiently form strong bidentate hydrogen bonds with carboxylates, phosphonates and sulfates on bacterial cell membranes, making it have more efficient antibacterial properties than cationic polymers containing halogenamine groups and quaternary ammonium (phosphonate) salts; in addition, guanidine-containing polymers have lower eukaryotic cell toxicity than amine-containing polymers.

[0025] 4. The anti-adhesion functional monomer used in the present invention is a polyethylene glycol methacrylate monomer, which relies on the CO structure on the main chain and can have a strong binding effect on water molecules through hydrogen bonding, static electricity and van der Waals forces to form a hydration layer, so that bacteria, proteins or cells must overcome these physical obstacles and energy barriers during the adhesion process on the material surface, thereby hindering the formation of protein and bacterial biofilms.

[0026] 5. The hydrophobic monomers used in the present invention are alkyl acrylate monomers and tertiary carbon group-containing functional ester monomers that constitute the main chain of the molecule; the acrylate monomers contain a large molecular hydrophobic group structure, and the double bonds participate in the polymerization reaction under the action of the initiator, and jointly form a polymer network structure through cross-linking with the hydrophilic monomer, which can convert the molecular interaction force between the polymer molecular chains into a strong chemical bond and can exist stably for a long time; the tertiary carbon structure of the functional ester monomer containing a tertiary carbon group has a highly branched carbon-rich umbrella-like structure on the α-carbon atom, which has a large steric hindrance and a strong shielding effect, can effectively prevent the hydrolysis of itself and the adjacent ester group, and has good water resistance. At the same time, the tertiary carbon group can reduce the surface tension of the polymer in which it is located, which is beneficial to improve the adhesion of the coating film to the substrate.

[0027] 6. The hydrophilic monomer used in the present invention is a bifunctional acrylate compound having hydrophilic groups such as carboxyl or hydroxyl groups. Under thermal initiation conditions, active free radicals are easily generated for polymerization reaction, and the carboxyl or hydroxyl groups can be cross-linked and cured. As the amount of monomer increases, the number of active sites for cross-linking reaction increases, the polymer coating molecules are arranged closely, the cross-linking degree of the polymerization system is improved, and the strength and water resistance of the coating film can be improved in the coating polymer.

[0028] 7. The leveling agent used in the present invention is an ethylene oxide adduct of acetylene glycol, which has low static and dynamic surface tension, and good wettability, which allows the coating to fully spread on the surface of the substrate; the adhesion promoter used is an acrylate mixture with a penetrating and etching effect, in which acrylates containing furan groups or 1,6-hexanediol diacrylate can produce micro-erosion on the substrate to roughen the surface of the substrate, promote the cross-linking components in the coating and the surface of the substrate to penetrate each other, form mutual entanglement, and enhance the adhesion between the coating and the substrate. After elution in physiological saline for 30 days, it can still have anti-adhesion and antibacterial properties of ≥90%.

[0029] 8. The polymerization process temperature of the method of the present invention is controllable, the reaction conditions are mild, and the obtained hyperbranched structure polymer functional emulsion can form an anti-adhesion barrier, which first effectively prevents bacterial aggregation, and at the same time plays an antibacterial role, avoids the accumulation of dead bacteria, and has a more lasting antibacterial effect. The polymer can be widely used in the coating of the surface of various Class III medical polymer materials, including polyurethane, silicone, polyethylene, etc.; the processing process is easy to industrialize and can meet the needs of more practical applications. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] In order to more clearly illustrate the technical solution of the present invention, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0031] Attached Figure 1 Schematic diagram of the preparation process of the antibacterial functional monomer in Example 1.

[0032] Attached Figure 2 Schematic diagram of the preparation process of the polyacrylate functional crosslinking agent in Example 1.

[0033] Attached Figure 3 These are graphs showing the anti-blood adhesion effects on the surfaces of the samples prepared in Examples 4, 7, 9 and 17.

[0034] Attached Figure 4 This is the infrared test spectrum of the antibacterial functional monomer in Example 1. DETAILED DESCRIPTION

[0035] The technical solutions in the embodiments of the present invention will be described clearly and completely below in conjunction with the accompanying drawings. The embodiments mentioned are all implemented on the premise of the technical solutions of the present invention, and detailed implementation processes are given, but it should be stated that the protection scope of the present invention is not limited to the following embodiments.

[0036] Example 1 (1) Preparation of antibacterial functional monomers (see the schematic diagram of the preparation process) Figure 1 ): Weigh 73.86g of 2000Da polyhexamethylene biguanide hydrochloride in a 250ml three-necked flask, add 120ml purified water and stir for 20min at a stirring rate of 200r / min to completely dissolve it. Place the dissolved polyhexamethylene biguanide hydrochloride in an ice-water bath at 5°C, add 5ml of 5.65mol / L sodium hydroxide solution to neutralize it, add it for 30min, continue to react for 20min, and after the reaction is completed, the solution is milky white, and the ice-water bath reaction is over. Then transfer the three-necked flask to a 35°C water bath, add 3.85ml of methacryloyl chloride, and mechanically stir the reaction at a speed of 200r / min for 1h to react with the secondary amine on the polymerized biguanide to form an amide bond, introduce a double bond group, and the solution gradually becomes clear. After the reaction is completed, precipitate it in tetrahydrofuran twice, then add petroleum ether to extract and wash the unreacted monomers, and vacuum dry it at 60°C overnight to obtain polyhexamethylene biguanide methacrylic acid (PHMB-MA). PHMB-MA was tested by infrared Figure 4 Representative data show that 3308cm -1 The peak at 2173 cm represents the characteristic absorption peak of NH2 in PHMB. -1 The NH and C=N stretching vibration absorption peaks in PHMB are 1548 cm -1 The NH bending vibration absorption peak in PHMB is 1154 cm -1represents the NH stretching vibration peak in PHMB. At the same time, it represents the C=C stretching vibration absorption peak 1620cm -1 and represents the C=O stretching vibration absorption peak at 1650 cm -1 The appearance of the acrylate group indicates that the grafting is successful. Due to the conjugation and neutralization effect of the carbon-carbon double bond and the amine group on C=O, the C=O stretching vibration absorption peak in the acrylate shifts to a lower wave number at 1650cm -1 Place.

[0037] (2) Preparation of polyacrylate functional crosslinking agent (see the schematic diagram of the preparation process Figure 2 ): Preparation of bidentate polyethylene glycol acrylate linear functional crosslinker: 32.4 g polyethylene glycol diamine and 2.41 g methacrylate-N-succinimidyl ester were weighed separately and dissolved in 68 mL dimethylformamide, 7.12 ml of N,N-diisopropylethylamine catalyst was added, and the reaction was carried out under nitrogen at room temperature for 12 hours. During this process, the acrylate group of methacrylate-N-succinimidyl ester was introduced into the polyethylene glycol diamine, and then placed in a dialysis bag with a cutoff of 2000 Da for 72 hours. After freeze-drying, the bidentate polyethylene glycol acrylate linear functional crosslinker was obtained.

[0038] Preparation of tetradentate polyethylene glycol acrylate star-shaped functional cross-linker: 28.73 g of four-arm polyethylene glycol tetramine and 2.11 g of methacrylate-N-succinimidyl ester were weighed separately and dissolved in 60.3 mL of dimethylformamide, 6.33 ml of N, N-diisopropylethylamine catalyst was added, and the reaction was carried out under nitrogen at room temperature for 12 hours. During this process, the acrylate group of methacrylate-N-succinimidyl ester was introduced into the four-arm polyethylene glycol tetramine, and then placed in a dialysis bag with a retention capacity of 2000 Da for 72 hours, and freeze-dried to obtain a tetradentate polyethylene glycol acrylate star-shaped functional cross-linker.

[0039] (3) Preparation of antibacterial and anti-adhesion functional emulsion: In a three-necked flask equipped with a mechanical stirring device, 8 parts of hydroxyethyl methacrylate, 30 parts of methyl methacrylate, 6 parts of tertiary glycerol acrylate and 300 parts of deionized water were first added in sequence, and stirred at a rate of 300 rpm / min for 30 minutes; then 12 parts of polyhexamethylene biguanide methacrylate (PHMB-MA) with a molecular weight of 2000, 15 parts of polyethylene glycol methyl ether methacrylate with a molecular weight of 2000, 0.8 parts of bidentate polyethylene glycol acrylate linear functional crosslinker, 0.9 parts of tetradentate polyethylene glycol acrylate star functional crosslinker and 0.9 parts of N,N-methylenebisacrylamide were added respectively, and the temperature began to rise while stirring. After the temperature reached 70°C, 0.37 parts of ammonium persulfate initiator was added, and the reaction was carried out for 4 hours under nitrogen protection, and then 0.1 parts of initiator was added to continue the reaction for 1 hour to obtain a milky white polymer solution. The polymer solution was placed in a dialysis bag and dialyzed for 72 hours with a molecular weight cutoff of 3000 Da. Excess water was removed by rotary evaporation, 0.6 parts of 2,4,7,9-tetramethyl-5-decyne-4,7-diol polyoxyethylene ether and 1 part of tetrahydrofurfuryl acrylate were added, and the mixture was stirred at a rotation speed of 200 rpm / min for 30 minutes to obtain an antibacterial and anti-adhesion functional emulsion.

[0040] Example 2 The preparation of antibacterial functional monomer and polyacrylate functional crosslinking agent is the same as that in Example 1. First, 8 parts of hydroxyethyl methacrylate, 32 parts of ethyl methacrylate, 8 parts of tert-butyl maleate and 300 parts of deionized water were added to a three-necked flask equipped with a mechanical stirring device, and stirred for 30 minutes at a rate of 300 rpm / min; then, 12 parts of polyhexamethylene biguanide methacrylate (PHMB-MA) with a molecular weight of 2000, 15 parts of polyethylene glycol methyl ether methacrylate with a molecular weight of 2000, 0.8 parts of bidentate polyethylene glycol acrylate linear functional crosslinking agent, 0.9 parts of tetradentate polyethylene glycol acrylate star-shaped functional crosslinking agent and 0.8 parts of N,N-methylenebisacrylamide were added respectively, and the temperature was stirred and began to rise. After the temperature reached 70°C, 0.31 parts of ammonium persulfate initiator were added, and the reaction was carried out for 4 hours under nitrogen protection, and then 0.1 parts of initiator were added to continue the reaction for 1 hour to obtain a milky white polymer solution. The polymer solution was placed in a dialysis bag and dialyzed for 72 hours with a molecular weight cutoff of 3000 Da. Excess water was removed by rotary evaporation, 0.5 parts of 2,4,7,9-tetramethyl-5-decyne-4,7-diol polyoxyethylene ether and 1 part of tetrahydrofurfuryl acrylate were added, and the mixture was stirred at a rotation speed of 200 rpm / min for 30 minutes to obtain an antibacterial and anti-adhesion functional emulsion.

[0041] Example 3 The preparation of antibacterial functional monomers and multi-acrylate functional crosslinking agents is the same as in Example 1. First, 8 parts of hydroxyethyl methacrylate, 20 parts of lauryl methacrylate, 6 parts of tert-butyl maleate and 300 parts of deionized water were added in sequence to a three-necked flask equipped with a mechanical stirring device, and stirred for 30 minutes at a rate of 300 rpm / min; then 12 parts of polyhexamethylene biguanide methacrylate (PHMB-MA) with a molecular weight of 2000, 15 parts of polyethylene glycol methyl ether methacrylate with a molecular weight of 2000, 0.8 parts of bidentate polyethylene glycol acrylate linear functional crosslinking agent, 0.9 parts of tetradentate polyethylene glycol acrylate star-shaped functional crosslinking agent and 0.8 parts of N,N-methylenebisacrylamide were added respectively, and the temperature was stirred and began to rise. After rising to 70°C, 0.3 parts of ammonium persulfate initiator were added, and the reaction was carried out for 4 hours under nitrogen protection, and then 0.07 parts of initiator were added to continue the reaction for 1 hour to obtain a milky white polymer solution. The polymer solution was placed in a dialysis bag and dialyzed for 72 hours with a molecular weight cutoff of 3000 Da. Excess water was removed by rotary evaporation, 0.5 parts of 2,4,7,9-tetramethyl-5-decyne-4,7-diol polyoxyethylene ether and 1 part of tetrahydrofurfuryl acrylate were added, and the mixture was stirred at a rotation speed of 200 rpm / min for 30 minutes to obtain an antibacterial and anti-adhesion functional emulsion.

[0042] Example 4 The preparation of antibacterial functional monomers and polyacrylate functional crosslinking agents is the same as in Example 1. First, 8 parts of hydroxyethyl methacrylate, 30 parts of butyl methacrylate, 8 parts of tertiary carbon glycerol methacrylate and 300 parts of deionized water were added in sequence to a three-necked flask equipped with a mechanical stirring device, and stirred for 25 minutes at a rate of 300rpm / min; then 12 parts of polyhexamethylene biguanide methacrylate (PHMB-MA) with a molecular weight of 2500, 15 parts of polyethylene glycol methyl ether methacrylate with a molecular weight of 2200, 1.3 parts of bidentate polyethylene glycol acrylate linear functional crosslinking agent, 1 part of tetradentate polyethylene glycol acrylate star-shaped functional crosslinking agent and 1 part of N,N-methylenebisacrylamide were added respectively, and the temperature was stirred and began to rise. After the temperature reached 70°C, 0.65 parts of ammonium persulfate initiator were added, and the reaction was carried out for 5 hours under nitrogen protection, and then 0.08 parts of initiator were added to continue the reaction for 1 hour to obtain a milky white polymer solution. The polymer solution was placed in a dialysis bag and dialyzed for 72 hours with a molecular weight cutoff of 3000 Da. Excess water was removed by rotary evaporation, 0.9 parts of 2,4,7,9-tetramethyl-5-decyne-4,7-diol polyoxyethylene ether and 1 part of tetrahydrofurfuryl acrylate were added, and the mixture was stirred at a rotation speed of 200 rpm / min for 30 minutes to obtain an antibacterial and anti-adhesion functional emulsion.

[0043] Example 5 The preparation of antibacterial functional monomers and multi-acrylate functional crosslinking agents is the same as in Example 1. First, 8 parts of hydroxyethyl methacrylate, 30 parts of butyl methacrylate, 6 parts of tert-butyl carbonate epoxy acrylate and 300 parts of deionized water were added in sequence to a three-necked flask equipped with a mechanical stirring device, and stirred for 25 minutes at a rate of 300 rpm / min; then 12 parts of polyhexamethylene biguanide methacrylate (PHMB-MA) with a molecular weight of 2500, 15 parts of polyethylene glycol methyl ether methacrylate with a molecular weight of 2200, 0.9 parts of bidentate polyethylene glycol acrylate linear functional crosslinking agent, 1 part of tetradentate polyethylene glycol acrylate star-shaped functional crosslinking agent and 1 part of N,N-methylenebisacrylamide were added respectively, and the temperature was stirred and began to rise. After the temperature reached 70°C, 0.42 parts of ammonium persulfate initiator were added, and the reaction was carried out for 5 hours under nitrogen protection, and then 0.1 parts of initiator were added to continue the reaction for 1 hour to obtain a milky white polymer solution. The polymer solution was placed in a dialysis bag and dialyzed for 72 hours with a molecular weight cutoff of 3000 Da. Excess water was removed by rotary evaporation, 0.8 parts of 2,4,7,9-tetramethyl-5-decyne-4,7-diol polyoxyethylene ether and 1 part of tetrahydrofurfuryl acrylate were added, and the mixture was stirred at a rotation speed of 200 rpm / min for 30 minutes to obtain an antibacterial and anti-adhesion functional emulsion.

[0044] Example 6 The preparation of antibacterial functional monomers and polyacrylate functional crosslinking agents is the same as in Example 1. First, 9 parts of acrylic acid, 30 parts of butyl methacrylate, 5 parts of tertiary glycerol acrylate and 300 parts of deionized water were added in sequence to a three-necked flask equipped with a mechanical stirring device, and stirred for 25 minutes at a rate of 300rpm / min; then 12 parts of polyhexamethylene biguanide methacrylate (PHMB-MA) with a molecular weight of 2500, 13 parts of polyethylene glycol methyl ether methacrylate with a molecular weight of 2000, 0.9 parts of bidentate polyethylene glycol acrylate linear functional crosslinking agent, 0.9 parts of tetradentate polyethylene glycol acrylate star-shaped functional crosslinking agent and 0.7 parts of N,N-methylenebisacrylamide were added respectively, and the temperature was stirred and began to rise. After the temperature reached 70°C, 0.6 parts of sodium persulfate initiator were added, and the reaction was carried out for 4 hours under nitrogen protection, and then 0.05 parts of initiator were added to continue the reaction for 1 hour to obtain a milky white polymer solution. The polymer solution was placed in a dialysis bag and dialyzed for 72 hours with a molecular weight cutoff of 3000 Da. Excess water was removed by rotary evaporation, 0.7 parts of 2,4,7,9-tetramethyl-5-decyne-4,7-diol polyoxyethylene ether and 0.8 parts of tetrahydrofurfuryl acrylate were added, and the mixture was stirred at a rotation speed of 200 rpm / min for 30 minutes to obtain an antibacterial and anti-adhesion functional emulsion.

[0045] Example 7 The preparation of antibacterial functional monomer and polyacrylate functional crosslinking agent is the same as that in Example 1. First, 9 parts of methacrylic acid, 30 parts of butyl methacrylate, 5 parts of tertiary carbon glycerol methacrylate and 300 parts of deionized water are added in sequence to a three-necked flask equipped with a mechanical stirring device, and stirred for 30 minutes at a rate of 300rpm / min; then, 12 parts of polyhexamethylene biguanide methacrylate (PHMB-MA) with a molecular weight of 2500, 13 parts of polyethylene glycol methyl ether methacrylate with a molecular weight of 2000, 0.8 parts of bidentate polyethylene glycol acrylate linear functional crosslinking agent, 1 part of tetradentate polyethylene glycol acrylate star-shaped functional crosslinking agent and 0.7 parts of N,N-methylenebisacrylamide are added respectively, and the temperature is stirred and started to rise. After rising to 75°C, 0.65 parts of sodium persulfate initiator are added, and the reaction is carried out for 4 hours under nitrogen protection, and then 0.08 parts of initiator are added to continue the reaction for 1 hour to obtain a milky white polymer solution. The polymer solution was placed in a dialysis bag and dialyzed for 72 hours with a molecular weight cutoff of 3000 Da. Excess water was removed by rotary evaporation, 0.7 parts of 2,4,7,9-tetramethyl-5-decyne-4,7-diol polyoxyethylene ether and 0.8 parts of tetrahydrofurfuryl acrylate were added, and the mixture was stirred at a rotation speed of 200 rpm / min for 30 minutes to obtain an antibacterial and anti-adhesion functional emulsion.

[0046] Example 8 The preparation of antibacterial functional monomers and polyacrylate functional crosslinking agents is the same as in Example 1. First, 7 parts of glycidyl methacrylate, 30 parts of butyl methacrylate, 5 parts of tertiary carbon glycerol methacrylate and 300 parts of deionized water were added in sequence to a three-necked flask equipped with a mechanical stirring device, and stirred for 28 minutes at a rate of 300rpm / min; then, 12 parts of polyhexamethylene biguanide methacrylate (PHMB-MA) with a molecular weight of 2500, 14 parts of polyethylene glycol methyl ether methacrylate with a molecular weight of 2000, 0.9 parts of bidentate polyethylene glycol acrylate linear functional crosslinking agent, 1 part of tetradentate polyethylene glycol acrylate star-shaped functional crosslinking agent and 0.7 parts of N,N-methylenebisacrylamide were added respectively, and the temperature was stirred and began to rise. After the temperature reached 75°C, 0.6 parts of sodium persulfate initiator were added, and the reaction was carried out for 4 hours under nitrogen protection, and then 0.08 parts of initiator were added to continue the reaction for 1 hour to obtain a milky white polymer solution. The polymer solution was placed in a dialysis bag and dialyzed for 72 hours with a molecular weight cutoff of 3000 Da. Excess water was removed by rotary evaporation, 0.7 parts of 2,4,7,9-tetramethyl-5-decyne-4,7-diol polyoxyethylene ether and 0.9 parts of tetrahydrofurfuryl acrylate were added, and the mixture was stirred at a rotation speed of 200 rpm / min for 30 minutes to obtain an antibacterial and anti-adhesion functional emulsion.

[0047] Example 9 The preparation of antibacterial functional monomers and polyacrylate functional crosslinking agents is the same as in Example 1. First, 8 parts of hydroxyethyl acrylate, 30 parts of butyl methacrylate, 5 parts of tertiary carbon glycerol methacrylate and 300 parts of deionized water were added in sequence to a three-necked flask equipped with a mechanical stirring device, and stirred for 27 minutes at a rate of 300rpm / min; then 15 parts of polyhexamethylene biguanide methacrylate (PHMB-MA) with a molecular weight of 2000, 15 parts of polyethylene glycol methyl ether methacrylate with a molecular weight of 2000, 1 part of bidentate polyethylene glycol acrylate linear functional crosslinking agent, 1 part of tetradentate polyethylene glycol acrylate star-shaped functional crosslinking agent and 1.5 parts of N,N-dihydroxyethyl bisacrylamide were added respectively, and the temperature was stirred and began to rise. After the temperature reached 80°C, 0.8 parts of ammonium persulfate initiator was added, and the reaction was carried out for 4 hours under nitrogen protection, and then 0.1 parts of initiator was added to continue the reaction for 1 hour to obtain a milky white polymer solution. The polymer solution was placed in a dialysis bag and dialyzed for 72 hours with a molecular weight cutoff of 3000 Da. Excess water was removed by rotary evaporation, 0.8 parts of 2,4,7,9-tetramethyl-5-decyne-4,7-diol polyoxyethylene ether and 1.2 parts of tetrahydrofurfuryl acrylate were added, and the mixture was stirred at a rotation speed of 200 rpm / min for 30 minutes to obtain an antibacterial and anti-adhesion functional emulsion.

[0048] Example 10 The preparation of antibacterial functional monomers and polyacrylate functional crosslinking agents is the same as in Example 1. First, 8 parts of hydroxyethyl methacrylate, 30 parts of butyl methacrylate, 5 parts of tertiary carbon glycerol methacrylate and 300 parts of deionized water were added in sequence to a three-necked flask equipped with a mechanical stirring device, and stirred for 30 minutes at a rate of 300 rpm / min; then 10 parts of polyhexamethylene biguanide methacrylate (PHMB-MA) with a molecular weight of 3000, 15 parts of polyethylene glycol methyl ether methacrylate with a molecular weight of 2000, 1 part of bidentate polyethylene glycol acrylate linear functional crosslinking agent, 1 part of tetradentate polyethylene glycol acrylate star-shaped functional crosslinking agent and 1.5 parts of N,N-dihydroxyethyl bisacrylamide were added respectively, and the temperature was stirred and began to rise. After the temperature reached 80°C, 0.8 parts of ammonium persulfate initiator was added, and the reaction was carried out for 4 hours under nitrogen protection, and then 0.1 parts of initiator was added to continue the reaction for 1 hour to obtain a milky white polymer solution. The polymer solution was placed in a dialysis bag and dialyzed for 72 hours with a molecular weight cutoff of 4000 Da. Excess water was removed by rotary evaporation, 0.8 parts of 2,4,7,9-tetramethyl-5-decyne-4,7-diol polyoxyethylene ether and 1.2 parts of tetrahydrofurfuryl acrylate were added, and the mixture was stirred at a rotation speed of 200 rpm / min for 30 minutes to obtain an antibacterial and anti-adhesion functional emulsion.

[0049] Embodiment 11 The preparation of antibacterial functional monomers and polyacrylate functional crosslinking agents is the same as in Example 1. First, 8 parts of hydroxyethyl methacrylate, 30 parts of butyl methacrylate, 5 parts of tertiary carbon glycerol methacrylate and 300 parts of deionized water were added in sequence to a three-necked flask equipped with a mechanical stirring device, and stirred for 30 minutes at a rate of 300 rpm / min; then 12 parts of polyhexamethylene biguanide methacrylate (PHMB-MA) with a molecular weight of 2500, 18 parts of polyethylene glycol methacrylate with a molecular weight of 500, 1.2 parts of bidentate polyethylene glycol acrylate linear functional crosslinking agent, 1.1 parts of tetradentate polyethylene glycol acrylate star-shaped functional crosslinking agent and 0.6 parts of N,N-methylenebisacrylamide were added respectively, and the temperature was stirred and began to rise. After the temperature reached 70°C, 0.5 parts of ammonium persulfate initiator were added, and the reaction was carried out for 6 hours under nitrogen protection, and then 0.07 parts of initiator were added to continue the reaction for 1 hour to obtain a milky white polymer solution. The polymer solution was placed in a dialysis bag and dialyzed for 72 hours with a molecular weight cutoff of 3000 Da. Excess water was removed by rotary evaporation, 0.7 parts of 2,4,7,9-tetramethyl-5-decyne-4,7-diol polyoxyethylene ether and 1.5 parts of tetrahydrofurfuryl acrylate were added, and the mixture was stirred at a rotation speed of 200 rpm / min for 30 minutes to obtain an antibacterial and anti-adhesion functional emulsion.

[0050] Example 12 The preparation of antibacterial functional monomers and polyacrylate functional crosslinking agents is the same as in Example 1. First, 8 parts of hydroxyethyl methacrylate, 30 parts of butyl methacrylate, 5 parts of tertiary carbon glycerol methacrylate and 300 parts of deionized water were added in sequence to a three-necked flask equipped with a mechanical stirring device, and stirred for 30 minutes at a rate of 300 rpm / min; then 12 parts of polyhexamethylene biguanide methacrylate (PHMB-MA) with a molecular weight of 2500, 12 parts of polyethylene glycol ethyl ether methacrylate with a molecular weight of 3000, 1.2 parts of bidentate polyethylene glycol acrylate linear functional crosslinking agent, 1.1 parts of tetradentate polyethylene glycol acrylate star-shaped functional crosslinking agent and 0.6 parts of N,N-methylenebisacrylamide were added respectively, and the temperature was stirred and began to rise. After the temperature reached 70°C, 0.48 parts of ammonium persulfate initiator was added, and the reaction was carried out for 6 hours under nitrogen protection, and then 0.13 parts of initiator were added to continue the reaction for 1 hour to obtain a milky white polymer solution. The polymer solution was placed in a dialysis bag and dialyzed for 72 hours with a molecular weight cutoff of 4000 Da. Excess water was removed by rotary evaporation, 0.9 parts of 2,4,7,9-tetramethyl-5-decyne-4,7-diol polyoxyethylene ether and 1.5 parts of tetrahydrofurfuryl acrylate were added, and the mixture was stirred at a rotation speed of 200 rpm / min for 30 minutes to obtain an antibacterial and anti-adhesion functional emulsion.

[0051] Embodiment 13 The preparation of antibacterial functional monomers and polyacrylate functional crosslinking agents is the same as in Example 1. First, 10 parts of hydroxypropyl methacrylate, 30 parts of butyl methacrylate, 5 parts of tertiary carbon glycerol methacrylate and 260 parts of deionized water were added in sequence to a three-necked flask equipped with a mechanical stirring device, and stirred for 30 minutes at a rate of 300rpm / min; then 12 parts of polyhexamethylene biguanide methacrylate (PHMB-MA) with a molecular weight of 2500, 16 parts of polyethylene glycol methacrylate with a molecular weight of 500, 0.5 parts of bidentate polyethylene glycol acrylate linear functional crosslinking agent, 0.5 parts of tetradentate polyethylene glycol acrylate star-shaped functional crosslinking agent and 0.5 parts of N,N-vinyl bisacrylamide were added respectively, and the temperature was stirred and began to rise. After the temperature reached 90°C, 0.2 parts of potassium persulfate initiator were added, and the reaction was carried out for 3 hours under nitrogen protection, and then 0.1 parts of initiator were added to continue the reaction for 2 hours to obtain a milky white polymer solution. The polymer solution was placed in a dialysis bag and dialyzed for 72 hours with a molecular weight cutoff of 3000 Da. Excess water was removed by rotary evaporation, 0.8 parts of 2,4,7,9-tetramethyl-5-decyne-4,7-diol polyoxyethylene ether and 0.7 parts of tetrahydrofurfuryl acrylate were added, and the mixture was stirred at a rotation speed of 200 rpm / min for 30 minutes to obtain an antibacterial and anti-adhesion functional emulsion.

[0052] Embodiment 14 The preparation of antibacterial functional monomers and polyacrylate functional crosslinking agents is the same as in Example 1. First, 10 parts of hydroxypropyl methacrylate, 30 parts of butyl methacrylate, 5 parts of tertiary carbon glycerol methacrylate and 260 parts of deionized water were added in sequence to a three-necked flask equipped with a mechanical stirring device, and stirred for 30 minutes at a rate of 300rpm / min; then 12 parts of polyhexamethylene biguanide methacrylate (PHMB-MA) with a molecular weight of 2500, 16 parts of polyethylene glycol methacrylate with a molecular weight of 500, 1.5 parts of bidentate polyethylene glycol acrylate linear functional crosslinking agent, 1.5 parts of tetradentate polyethylene glycol acrylate star-shaped functional crosslinking agent and 0.5 parts of N,N-vinyl bisacrylamide were added respectively, and the temperature was stirred and started to rise. After rising to 90°C, 0.2 parts of potassium persulfate initiator were added, and the reaction was carried out for 3 hours under nitrogen protection, and then 0.1 parts of initiator were added to continue the reaction for 2 hours to obtain a milky white polymer solution. The polymer solution was placed in a dialysis bag and dialyzed for 72 hours with a molecular weight cutoff of 3000 Da. Excess water was removed by rotary evaporation, 0.8 parts of 2,4,7,9-tetramethyl-5-decyne-4,7-diol polyoxyethylene ether and 0.7 parts of tetrahydrofurfuryl acrylate were added, and the mixture was stirred at a rotation speed of 200 rpm / min for 30 minutes to obtain an antibacterial and anti-adhesion functional emulsion.

[0053] Embodiment 15 The preparation of antibacterial functional monomers and polyacrylate functional crosslinking agents is the same as in Example 1. First, 8 parts of hydroxyethyl acrylate, 30 parts of butyl methacrylate, 5 parts of tertiary carbon glycerol methacrylate and 400 parts of deionized water were added in sequence to a three-necked flask equipped with a mechanical stirring device, and stirred for 20 minutes at a rate of 300rpm / min; then 15 parts of polyhexamethylene biguanide methacrylate (PHMB-MA) with a molecular weight of 2000, 15 parts of polyethylene glycol methyl ether methacrylate with a molecular weight of 2000, 0.8 parts of bidentate polyethylene glycol acrylate linear functional crosslinking agent, 1.2 parts of tetradentate polyethylene glycol acrylate star-shaped functional crosslinking agent and 1.5 parts of N,N-dihydroxyethyl bisacrylamide were added respectively, and the temperature was stirred and began to rise. After the temperature reached 70°C, 0.72 parts of ammonium persulfate initiator were added, and the reaction was carried out for 4 hours under nitrogen protection, and then 0.1 parts of initiator were added to continue the reaction for 1 hour to obtain a milky white polymer solution. The polymer solution was placed in a dialysis bag and dialyzed for 72 hours with a molecular weight cutoff of 3000 Da. Excess water was removed by rotary evaporation, and 1 part of 2,4,7,9-tetramethyl-5-decyne-4,7-diol polyoxyethylene ether and 1.2 parts of 2-tetrahydrofuran methylacrylate were added. The mixture was stirred at a rotation speed of 200 rpm / min for 30 minutes to obtain an antibacterial and anti-adhesion functional emulsion.

[0054] Example 16 The preparation of antibacterial functional monomers and polyacrylate functional crosslinking agents is the same as in Example 1. First, 8 parts of hydroxyethyl methacrylate, 30 parts of butyl methacrylate, 5 parts of tertiary carbon glycerol methacrylate and 400 parts of deionized water were added in sequence to a three-necked flask equipped with a mechanical stirring device, and stirred for 20 minutes at a rate of 300rpm / min; then 12 parts of polyhexamethylene biguanide methacrylate (PHMB-MA) with a molecular weight of 2500, 15 parts of polyethylene glycol methyl ether methacrylate with a molecular weight of 2000, 0.8 parts of bidentate polyethylene glycol acrylate linear functional crosslinking agent, 1.2 parts of tetradentate polyethylene glycol acrylate star-shaped functional crosslinking agent and 0.6 parts of N,N-methylenebisacrylamide were added respectively, and the temperature was stirred and began to rise. After the temperature reached 70°C, 0.74 parts of ammonium persulfate initiator were added, and the reaction was carried out for 4 hours under nitrogen protection, and then 0.1 parts of initiator were added to continue the reaction for 1 hour to obtain a milky white polymer solution. The polymer solution was placed in a dialysis bag and dialyzed for 72 hours with a molecular weight cutoff of 3000 Da. Excess water was removed by rotary evaporation, and 1 part of 2,4,7,9-tetramethyl-5-decyne-4,7-diol polyoxyethylene ether and 1.2 parts of 1,6-hexanediol diacrylate were added. The mixture was stirred at a rotation speed of 200 rpm / min for 30 minutes to obtain an antibacterial and anti-adhesion functional emulsion.

[0055] Embodiment 17 The preparation of antibacterial functional monomer and polyacrylate functional crosslinking agent is the same as that in Example 1. First, 7 parts of glycidyl methacrylate, 30 parts of butyl methacrylate, 5 parts of tertiary carbon glycerol methacrylate and 400 parts of deionized water are added in sequence to a three-necked flask equipped with a mechanical stirring device, and stirred for 20 minutes at a rate of 300rpm / min; then 12 parts of polyhexamethylene biguanide methacrylate (PHMB-MA) with a molecular weight of 2500, 15 parts of polyethylene glycol methyl ether methacrylate with a molecular weight of 2000, 0.8 parts of bidentate polyethylene glycol acrylate linear functional crosslinking agent, 1.2 parts of tetradentate polyethylene glycol acrylate star-shaped functional crosslinking agent and 0.6 parts of N,N-methylenebisacrylamide are added respectively, and the temperature is stirred and started to rise. After rising to 70°C, 0.75 parts of ammonium persulfate initiator are added, and the reaction is carried out for 4 hours under nitrogen protection, and then 0.1 parts of initiator are added to continue the reaction for 1 hour to obtain a milky white polymer solution. The polymer solution was placed in a dialysis bag and dialyzed for 72 hours with a molecular weight cutoff of 3000 Da. Excess water was removed by rotary evaporation, and 1 part of 2,4,7,9-tetramethyl-5-decyne-4,7-diol polyoxyethylene ether, 0.7 parts of 2-tetrahydrofuran methyl acrylate and 0.7 parts of 1,6-hexanediol diacrylate were added respectively. The mixture was stirred at a rotation speed of 200 rpm / min for 30 minutes to obtain an antibacterial and anti-adhesion functional emulsion.

[0056] Comparative Example 1 The preparation of the polyacrylate functional crosslinking agent is the same as in Example 1. The preparation of the antibacterial functional monomer is different from that in Example 1 in that the molecular weight of the polyhexamethylene biguanide hydrochloride is 750 Da. In a three-necked flask equipped with a mechanical stirring device, 8 parts of hydroxyethyl methacrylate, 30 parts of butyl methacrylate, 5 parts of tertiary carbon glycerol methacrylate and 300 parts of deionized water were first added in sequence, and stirred at a rate of 300 rpm / min for 25 minutes; then 12 parts of polyhexamethylene biguanide methacrylate (PHMB-MA) with a molecular weight of 750, 10 parts of polyethylene glycol methyl ether methacrylate with a molecular weight of 2000, 1 part of bidentate polyethylene glycol acrylate linear functional crosslinker, 1 part of tetradentate polyethylene glycol acrylate star functional crosslinker and 0.6 parts of N,N-methylenebisacrylamide were added respectively, and the temperature began to rise while stirring. After the temperature reached 70°C, 0.8 parts of ammonium persulfate initiator was added, and the reaction was carried out for 4 hours under nitrogen protection, and then 0.1 parts of initiator was added to continue the reaction for 1 hour to obtain a milky white polymer solution. The polymer solution was placed in a dialysis bag and dialyzed for 72 hours with a molecular weight cutoff of 3000 Da. Excess water was removed by rotary evaporation, and 1 part of 2,4,7,9-tetramethyl-5-decyne-4,7-diol polyoxyethylene ether and 1.2 parts of tetrahydrofurfuryl acrylate were added. The mixture was stirred at a rotation speed of 200 rpm / min for 30 minutes to obtain an antibacterial and anti-adhesion functional emulsion.

[0057] Comparative Example 2 The preparation of antibacterial functional monomer and polyacrylate functional crosslinking agent is the same as that in Example 1. First, 8 parts of hydroxyethyl methacrylate, 30 parts of butyl methacrylate, 5 parts of tertiary carbon glycerol methacrylate and 300 parts of deionized water are added in sequence to a three-necked flask equipped with a mechanical stirring device, and stirred for 25 minutes at a rate of 300rpm / min; then 12 parts of polyhexamethylene biguanide methacrylate (PHMB-MA) with a molecular weight of 2500, 10 parts of polyethylene glycol methyl ether methacrylate with a molecular weight of 400, 1.2 parts of bidentate polyethylene glycol acrylate linear functional crosslinking agent, 1.1 parts of tetradentate polyethylene glycol acrylate star-shaped functional crosslinking agent and 0.6 parts of N,N-methylenebisacrylamide are added respectively, and the temperature is stirred and started to rise. After rising to 80°C, 0.3 parts of ammonium persulfate initiator are added, and the reaction is carried out for 4 hours under nitrogen protection, and then 0.09 parts of initiator are added to continue the reaction for 2 hours to obtain a milky white polymer solution. The polymer solution was placed in a dialysis bag and dialyzed for 72 hours with a molecular weight cutoff of 3000 Da. Excess water was removed by rotary evaporation, 0.5 parts of 2,4,7,9-tetramethyl-5-decyne-4,7-diol polyoxyethylene ether and 1 part of tetrahydrofurfuryl acrylate were added, and the mixture was stirred at a rotation speed of 200 rpm / min for 30 minutes to obtain an antibacterial and anti-adhesion functional emulsion.

[0058] Comparative Example 3 The preparation of antibacterial functional monomer and polyacrylate functional crosslinking agent is the same as that in Example 1. First, 8 parts of hydroxyethyl methacrylate, 30 parts of butyl methacrylate, 5 parts of tertiary carbon glycerol methacrylate and 300 parts of deionized water were added in sequence to a three-necked flask equipped with a mechanical stirring device, and stirred for 25 minutes at a rate of 300rpm / min; then, 12 parts of polyhexamethylene biguanide methacrylate (PHMB-MA) with a molecular weight of 2500, 10 parts of polyethylene glycol methyl ether methacrylate with a molecular weight of 6000, 1.2 parts of bidentate polyethylene glycol acrylate linear functional crosslinking agent, 1.1 parts of tetradentate polyethylene glycol acrylate star-shaped functional crosslinking agent and 0.6 parts of N,N-methylenebisacrylamide were added respectively, and the temperature was stirred and began to rise. After the temperature reached 80°C, 0.3 parts of ammonium persulfate initiator was added, and the reaction was carried out for 4 hours under nitrogen protection, and then 0.09 parts of initiator were added to continue the reaction for 2 hours to obtain a milky white polymer solution. The polymer solution was placed in a dialysis bag and dialyzed for 72 hours with a molecular weight cutoff of 3000 Da. Excess water was removed by rotary evaporation, 0.5 parts of 2,4,7,9-tetramethyl-5-decyne-4,7-diol polyoxyethylene ether and 1 part of tetrahydrofurfuryl acrylate were added, and the mixture was stirred at a rotation speed of 200 rpm / min for 30 minutes to obtain an antibacterial and anti-adhesion functional emulsion.

[0059] Comparative Example 4 The preparation method of this comparative example is the same as the preparation method of Example 3, except that step (2) the preparation process of the polyacrylate functional crosslinking agent is omitted, and the polyacrylate functional crosslinking agent is not added.

[0060] Comparative Example 5 The preparation method of this comparative example is the same as that of Example 11, except that 30 parts of polyethylene glycol methyl ether methacrylate with a molecular weight of 2000 is added in step (3).

[0061] Comparative Example 6 The preparation method of this comparative example is the same as that of Example 3, except that tertiary methacrylate is not added in step (3).

[0062] Comparative Example 7 The preparation method of this comparative example is the same as the preparation method of Example 14, except that 2,4,7,9-tetramethyl-5-decyne-4,7-diol polyoxyethylene ether is not added in step (4).

[0063] Comparative Example 8 The preparation method of this comparative example is the same as the preparation method of Example 14, except that 2-tetrahydrofuran methyl acrylate is not added in step (4).

[0064] Implementation effect example The performance indicators of Examples 1-17 and Comparative Examples 1-8 were measured by the following methods.

[0065] (1) Antibacterial properties Refer to the provisions of "GB / T31402-2015 Test method for antibacterial properties of plastic surfaces".

[0066] (2) Platelet count Refer to the provisions of "YY / T1649.1-2019 Medical Device and Platelet Interaction Test Part 1: In Vitro Platelet Counting Method".

[0067] (3) Contact angle Refer to the provisions of "GB / T 30693-2014 Measurement of contact angle between plastic film and water".

[0068] (4) Coating firmness Refer to the provisions of GB / T 9286-2021 "Scratch test for paints and varnishes".

[0069] The above performance test results are shown in Table 1: Table 1 Test results of antibacterial property, platelet, contact angle and coating firmness From the test results of Examples 1-17 in Table 1, it can be concluded that the antibacterial and anti-adhesion functional emulsion provided by the present invention, which is prepared by adding a suitable proportion of monomers and functional monomer compositions, a multi-acrylate functional crosslinking agent and related additives in the components, has excellent antibacterial and anti-adhesion properties and stable coating firmness.

[0070] Combined with the data of Comparative Example 1, it can be seen that when polyhexamethylene biguanide hydrochloride with a smaller molecular weight is selected, the charge density of the antibacterial agent molecule is lower than the antibacterial threshold, and it is difficult to achieve an excellent bacterial contact killing effect.

[0071] Combining the data of Comparative Examples 2, 3 and 5, it can be seen that the molecular weight of the anti-adhesion functional monomer has an important influence on its properties and applications. When a polyethylene glycol methacrylate monomer of less than 500Da is selected, water droplets will gather on the surface of the sample, resulting in a significant decrease in the contact angle. This is because low-molecular polyethylene glycol methacrylate monomers have strong hygroscopicity; when a polyethylene glycol methacrylate monomer of greater than 3000Da is selected, due to the increase in molecular length, the hydroxyl groups on the molecular segments are not easy to approach each other, the movement of the molecular segments is hindered, and the effect of hydrogen bonding is not obvious, resulting in the surface of the treated sample being sticky and the anti-adhesion effect being poor; when the amount of polyethylene glycol methacrylate monomer added is too large, it is easy to cause polymer agglomeration, the surface of the coated sample presents a rough granular feel, and the coating firmness decreases.

[0072] Combined with the data of Comparative Example 4, it can be seen that without adding the multi-acrylate functional cross-linking agent, the platelet count is significantly reduced, indicating that the functional emulsion does not play a complete anti-adhesion effect, while the homemade bidentate polyethylene glycol acrylate linear functional cross-linking agent and the tetradentate polyethylene glycol acrylate star functional cross-linking agent can effectively create a bacteria-repellent material surface, which can comprehensively prevent the adhesion of bacteria and proteins on the material surface.

[0073] Combined with the data of Comparative Example 6, it can be seen that failure to add functional hydrophobic monomers will lead to a decrease in overall performance. This is because the functional hydrophobic monomers can promote the main chain to have good affinity and water resistance to the substrate after polymerization, and the tertiary carbon group can reduce the surface tension of the polymer, which is beneficial to improve the adhesion of the antibacterial and anti-adhesion functional emulsion to the substrate.

[0074] Combining the data of Comparative Examples 7 and 8, it can be seen that failure to add a leveling agent will lead to poor uniformity of the sample. The purpose of adding a leveling agent is to reduce the surface tension of the functional emulsion and encourage the functional emulsion to form a flat, smooth and uniform coating film. However, failure to add an adhesion promoter results in the treated sample having almost no antibacterial and anti-adhesion effects. This is because the functional emulsion cannot produce a micro-erosion effect on the substrate to roughen the surface of the substrate, and the cross-linked components in the functional emulsion cannot penetrate the surface of the substrate, thereby failing to act on the surface of the material to exert their effects.

[0075] Example 4, Example 7, Example 9 and Example 17 were selected as representatives, and were coated on the surface of the polyurethane sample by dipping according to the method given in the relevant examples, cured at 70° C. for 6 hours, and then measured according to the following method.

[0076] (5) Antibacterial activity after 30 days of elution The polyurethane samples were placed in physiological saline, which should submerge the samples. The samples were shaken on a mechanical oscillator at a reciprocating rate of 60 times / min and at 37±1°C for 30 days, and then the antibacterial tests were performed.

[0077] (6) Anti-blood adhesion Add 3 mL of sterile anticoagulated sheep blood and 30 μL of CaCl2 standard titration solution (1 mol / L) to 5 mL centrifuge tubes respectively and mix well. At the same time, use a needle to fix the blank and sample on the cap of the centrifuge tube, then immerse each tube completely in the sheep blood and let it stand. Take it out and observe it regularly. After the surface of the TPU tube is adhered by sheep blood, take out all the samples and rinse them three times in purified water. Finally, wipe the surface of each tube dry for comparison.

[0078] (7) Hemolysis rate Refer to the provisions of Part VII of GB / T 14233.2-2005 Test methods for medical infusion, transfusion and injection equipment Part 2: Biological test methods.

[0079] (8) Cell survival rate Refer to the provisions of "GB / T 16886.5-2017 Biological evaluation of medical devices Part 5: In vitro cytotoxicity test".

[0080] The above performance test results are shown in Table 2 and Figure 3 As shown: Table 2 Hemolysis rate, cell survival rate, antibacterial test results after 30 days of elution From Table 2 and Figure 3 It can be seen that the antibacterial and anti-adhesion functional emulsion obtained by the preparation method provided by the present invention still has an antibacterial effect of >99% and excellent anti-blood adhesion effect on Staphylococcus aureus, Escherichia coli and Candida albicans after elution in physiological saline for 30 days, and the cytotoxicity and hemolysis are both within the qualified range.

[0081] The above description of the disclosed embodiments enables those skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. An antibacterial and anti-adhesion functional emulsion, characterized in that: The antibacterial functional monomer and the anti-adhesion functional monomer are used as the core raw materials, deionized water is used as the solvent, hydrophobic units, hydrophilic units, leveling agents and adhesion promoters are added in proportion, and the obtained product is prepared by polymerization cross-linking under the joint action of a polyacrylate functional cross-linking agent, an internal cross-linking agent and an initiator.

2. The antibacterial and anti-adhesion functional emulsion according to claim 1, characterized in that: The raw material components include the following compositions in parts by weight: 10-15 parts of antibacterial functional monomers, 12-18 parts of anti-adhesion functional monomers, 25-40 parts of hydrophobic units, 6-10 parts of hydrophilic units, 0.1-1.0 parts of leveling agents, 0.5-1.5 parts of adhesion promoters, 1-3 parts of polyacrylate functional crosslinking agents, 0.5-1.5 parts of internal crosslinking agents, 0.3-0.9 parts of initiators, and 260-400 parts of deionized water.

3. The antibacterial and anti-adhesion functional emulsion according to claim 1, characterized in that: The antibacterial functional monomer includes polyhexamethylene biguanide methacrylic acid, which is prepared by first neutralizing polyhexamethylene biguanide hydrochloride with a molecular weight of 2000-3000 Da with a strong base to obtain polymerized biguanide, then adding methacrylic chloride at a molar ratio of 1:1-1.5 at 37±2°C to react with the polymerized biguanide; and then extracting, separating, purifying, rotary evaporating and freeze-drying to obtain the obtained product.

4. The antibacterial and anti-adhesion functional emulsion according to claim 1, characterized in that: The polyacrylate functional crosslinking agent includes a bidentate polyethylene glycol acrylate linear functional crosslinking agent and a tetradentate polyethylene glycol acrylate star-shaped functional crosslinking agent. The polyethylene glycol diamine or four-arm polyethylene glycol tetraamine and methacrylate-N-succinimide ester are dissolved in dimethylformamide, and reacted for 8-12 hours at room temperature under nitrogen protection under the catalysis of N,N-diisopropylethylamine to obtain a crude product. The crude product is then placed in a dialysis bag with a cutoff of 2000Da for treatment for 48-72 hours, and freeze-dried and purified to obtain a bidentate polyethylene glycol acrylate linear functional crosslinking agent or a tetradentate polyethylene glycol acrylate star-shaped functional crosslinking agent.

5. The antibacterial and anti-adhesion functional emulsion according to claim 4, characterized in that: The molar ratio of the polyethylene glycol diamine to the methacrylate-N-succinimide ester is 1:2-3; the molar ratio of the four-arm polyethylene glycol tetraamine to the methacrylate-N-succinimide ester is 1:4-5.

6. The antibacterial and anti-adhesion functional emulsion according to claim 1, characterized in that: The anti-adhesion functional monomer includes a polyethylene glycol methacrylate monomer with a molecular weight of 500-3000 Da; the polyethylene glycol methacrylate monomer includes any one of polyethylene glycol methacrylate, polyethylene glycol methyl ether methacrylate and polyethylene glycol ethyl ether methacrylate.

7. The antibacterial and anti-adhesion functional emulsion according to claim 1, characterized in that: The hydrophobic unit is composed of an alkyl acrylate monomer and a functional ester monomer containing a tertiary carbon group; the alkyl acrylate monomer includes any one of methyl methacrylate, ethyl methacrylate, butyl methacrylate and lauryl methacrylate, and the functional ester monomer containing a tertiary carbon group includes any one of tertiary carbon glyceryl acrylate, tertiary carbon glyceryl methacrylate, tertiary carbonic acid maleate and tertiary carbonic acid epoxy acrylate.

8. The antibacterial and anti-adhesion functional emulsion according to claim 1, characterized in that: The internal crosslinking agent includes any one of N,N-methylenebisacrylamide, N,N-dihydroxyethylbisacrylamide and N,N-vinylbisacrylamide; the leveling agent is 2,4,7,9-tetramethyl-5-decyne-4,7-diol polyoxyethylene ether; the adhesion promoter includes any one or more of tetrahydrofurfuryl acrylate, 2-tetrahydrofuran methacrylate and 1,6-hexanediol diacrylate; the initiator includes any one of ammonium persulfate, potassium persulfate and sodium persulfate; the hydrophilic unit includes any one of acrylic acid, methacrylic acid, hydroxyethyl acrylate, hydroxyethyl methacrylate, hydroxypropyl methacrylate and glycidyl methacrylate.

9. A method for preparing the antibacterial and anti-adhesion functional emulsion according to any one of claims 1 to 8, characterized in that: The steps include: S1, adding a hydrophilic unit, a hydrophobic unit and deionized water into a reaction container, and stirring at a stirring rate of 300±20rpm / min for 20-30min to obtain a solution A; S2, adding antibacterial functional monomer, anti-adhesion functional monomer, polyacrylate functional crosslinking agent and internal crosslinking agent to solution A, stirring and gradually heating to 70-90° C. to obtain solution B; S3, adding part of the initiator to solution B, reacting for 3-6 hours under nitrogen protection, adding the remaining amount of initiator, and continuing the reaction for 1-2 hours to obtain solution C; S4, placing solution C in a dialysis bag for 48-72 hours, with a molecular weight cutoff of 3000-4000Da, removing excess water, adding a leveling agent and an adhesion promoter, and mixing well to obtain an antibacterial and anti-adhesion functional emulsion.

10. Application of an antibacterial and anti-adhesion functional emulsion in antibacterial and anti-adhesion medical products, characterized in that: The antibacterial and anti-adhesion functional emulsion according to any one of claims 1 to 8 is applied to the surface of the medical product by dipping, brushing, rolling or spraying, and cured at 50-70° C. for 6-8 hours to obtain the antibacterial and anti-adhesion functional emulsion.

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