Composite material for antibacterial nursing apparatus and preparation method thereof

Abstract

The preparation method comprises the following steps: (1) dissolving liposome in a chloroform-methanol mixed solvent, carrying out rotary evaporation to remove the solvent so as to form a lipid film, dispersing an antibacterial substance in a buffer solution so as to obtain a mixed solution, and drying the mixed solution so as to obtain a lipid film; adding the mixed solution into the dried lipid film, and carrying out vortex oscillation to form a multi-chamber liposome; (2) dissolving polyglutamic acid and a cross-linking agent in water, dropwise adding dimethyl sulfoxide, stirring, adding the multi-chamber liposome in the stirring process, slowly dropwise adding a catalyst, carrying out a catalytic reaction, and collecting solid particles after the reaction; and dispersing the solid particles in an adhesive to obtain the composite material for the antibacterial nursing apparatus. According to the composite material, polyglutamic acid is cross-linked to form a three-dimensional network structure, and liposome is embedded into the three-dimensional network structure, so that the release of an antibacterial agent can be further delayed, the antibacterial period is prolonged, and the requirement of frequently replacing instruments is reduced.

Description

Technical Field

[0001] The present application belongs to the field of medical care equipment materials, and specifically relates to a composite material for antibacterial care equipment and a preparation method thereof. Background Art

[0002] Medical devices refer to instruments, equipment, apparatus, in vitro diagnostic reagents and other similar or related items used to diagnose, prevent or treat various diseases or other medical conditions, but do not achieve their purposes through biochemical effects in the body such as drugs.

[0003] Medical device infection is one of the most common and serious clinical complications. Currently, antibiotics are a common means of clinically treating infections. Their widespread use and abuse lead to bacterial mutations and drug resistance. In addition, although bactericides such as antimicrobial peptides have high bactericidal efficiency, they are toxic to normal tissue cells and cause bacterial resistance, leading to inflammation and immune responses.

[0004] There are three main types of antimicrobial medical materials: bactericidal surfaces, antibacterial adhesion surfaces, and both antimicrobial adhesion and bactericidal surfaces. Antimicrobial nursing devices, with antimicrobial properties, are used in medical or daily care settings to prevent or reduce microbial infections. These antimicrobial or bactericidal properties are typically achieved through material modification, surface coatings, or the addition of antimicrobial ingredients.

[0005] Among the currently disclosed technical information, there are also some that use polyglutamic acid as a coating for medical care devices, such as patent number CN117180520A, patent name is a preparation method and application of a γ-polyglutamic acid-quaternary ammonium salt-mussel protein coating, and patent number CN115058036A, patent name is a cross-linked polyglutamic acid composite gel membrane and its preparation method and application.

[0006] In actual applications, the antibacterial effect of technologies similar to the above is very general, and the antibacterial durability is poor. Summary of the Invention

[0007] In order to solve the above problems, the present application proposes a method for preparing a composite material for antibacterial care devices, comprising the following steps:

[0008] (1) dissolving liposomes in a chloroform-methanol mixed solvent, removing the solvent by rotary evaporation to form a lipid film, dispersing the antibacterial substance in a buffer solution to obtain a mixed solution, adding the mixed solution to the dried lipid film, and vortexing to form multilamellar liposomes;

[0009] (2) Dissolving polyglutamic acid and a cross-linking agent in water, then adding dimethyl sulfoxide (DMSO) dropwise and stirring, adding multilamellar liposomes during the stirring process, then slowly adding a catalyst dropwise to carry out a catalytic reaction, and collecting solid particles after the reaction; dispersing the solid particles in an adhesive to obtain a composite material for antibacterial nursing devices.

[0010] Preferably, the volume ratio of chloroform to methanol in the chloroform-methanol mixed solvent is (1-4):1; 10-30 mL of the chloroform-methanol mixed solvent is used for every 100 mg of liposomes.

[0011] Preferably, the rotary evaporation temperature is 30-50° C., the vacuum degree is 0.05-0.1 MPa, and the rotation speed is 60-100 rpm.

[0012] Preferably, the buffer is phosphate buffered saline (PBS) with a pH of 7.2-7.4. Every 10 mg of the antibacterial substance is dispersed in 1-10 mL of the buffer.

[0013] Preferably, the mass ratio of the dried lipid film to the antibacterial substance is (3-8):1.

[0014] Preferably, the vortexing time is 5-10 minutes.

[0015] Preferably, the mass ratio of polyglutamic acid to the cross-linking agent is (5-10):1.

[0016] Preferably, the mass ratio of polyglutamic acid to water is (5-10):1.

[0017] Preferably, the mass ratio of polyglutamic acid to dimethyl sulfoxide is (20-100):1.

[0018] Preferably, the mass ratio of polyglutamic acid to multilamellar liposome is (2-5):1.

[0019] Preferably, the cross-linking agent is genipin or polyethylene glycol diglycidyl ether.

[0020] Preferably, the catalyst is 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) or N-hydroxysuccinimide (NHS).

[0021] Preferably, the mass ratio of the catalyst to the cross-linking agent is (1-3):1; and the catalytic reaction time is 10-20 hours.

[0022] Preferably, the solid particles can be collected by centrifugation with the rotation speed controlled at 5000-8000 rpm for 10-20 minutes.

[0023] Preferably, the adhesive is one or more of gelatin, sodium alginate, polyurethane, epoxy resin, polylactic acid-glycolic acid copolymer, and acrylic resin.

[0024] Preferably, the mass ratio of solid particles to adhesive is 1:(5-10).

[0025] Furthermore, in step (1), the liposomes are phospholipids and / or cholesterol.

[0026] The antibacterial substance is silver nanoparticles and / or quaternary ammonium salt, and the quaternary ammonium salt is benzalkonium chloride and / or cetyltrimethylammonium bromide.

[0027] Furthermore, the multilamellar liposomes obtained in step (1) are subjected to an amination treatment, the steps of which are:

[0028] S1. Dispersing the multilamellar liposomes in an acetic acid solution with a pH of 5, adding a silver nitrate solution and a hydrogen peroxide solution under stirring, placing the solution in a water bath at 50-60° C. for 2-5 hours, collecting the precipitate by centrifugation, and drying the solution to obtain the carboxylated multilamellar liposomes;

[0029] S2. Disperse the carboxylated multilamellar liposomes obtained in step S1 in phosphate buffer, add EDC and NHS for activation for 20-50 min; add polyethyleneimine, react at room temperature for 8-14 h, collect the precipitate by centrifugation, and dry at room temperature to obtain amino multilamellar liposomes.

[0030] Preferably, in step S1, the mass ratio of multilamellar liposomes to acetic acid is 1:(20-30).

[0031] Preferably, the concentration of the silver nitrate solution is 0.1-0.3 mol / L, and the mass ratio of silver nitrate to multilamellar liposome is 1:(10-15).

[0032] Preferably, the mass fraction of hydrogen peroxide in the hydrogen peroxide solution is 3-5%, and the mass ratio of hydrogen peroxide to multilamellar liposomes is 1:(20-30).

[0033] Preferably, the pH of the phosphate buffer solution (PBS) in step S2 is 7.2-7.4, and the mass ratio of the carboxylated multilamellar liposome to the phosphate buffer solution is 1:(15-30).

[0034] Preferably, the molar ratio of EDC to NHS is 1:(1-1.5), and the sum of the mass of EDC and NHS accounts for 0.05-0.3% of the mass of the carboxylated multilamellar liposomes.

[0035] Preferably, the mass ratio of polyethyleneimine to carboxylated multilamellar vesicles is 1:(1-2).

[0036] The composite material obtained in this application is used in medical care devices, specifically wound dressings, medical bandages, tissue engineering scaffolds, medical device coatings, indwelling catheters, or sutures.

[0037] This application selects different adhesives according to the needs of different nursing devices. Gelatin is used as adhesive for wound dressings, medical bandages and other nursing devices; sodium alginate is used as adhesive for tissue engineering scaffolds and other nursing devices; polyurethane is used as adhesive for the assembly and coating of medical devices; epoxy resin is used as adhesive for dental devices and surgical instruments; polylactic acid-glycolic acid copolymer is used as adhesive for absorbable sutures.

[0038] This application can bring the following beneficial effects:

[0039] 1. The present application prepares multi-compartment liposomes, i.e., multi-layer phospholipid bilayer structures, which can encapsulate antimicrobial substances and achieve sustained release of antimicrobial ingredients through slow degradation or osmotic action of the lipid membrane; and the hydrophobic layer of the liposomes can protect the antimicrobial substances from aggregation and inactivation, which can extend the antimicrobial cycle and reduce the need for frequent device replacement.

[0040] 2. Polyglutamic acid forms a three-dimensional network structure after cross-linking, and liposomes embedded in it can further delay the release of antibacterial agents. The cross-linked network formed by the cross-linker is pH-responsive and can accelerate degradation in a slightly acidic environment at the infection site, thereby achieving targeted release.

[0041] 3. The antibacterial substance of this application is silver nanoparticles, which release silver ions to destroy bacterial cell membranes, interfere with the respiratory chain and DNA replication, and are effective against drug-resistant bacteria and fungi. Liposome coating reduces the oxidative inactivation of silver nanoparticles and maintains long-term activity.

[0042] 4. The antibacterial agent used in this application is a quaternary ammonium salt. The positively charged quaternary ammonium group binds to the negatively charged bacterial membrane, causing membrane rupture and leakage of cellular contents. Combined with silver nanoparticles, it can protect against Gram-positive and Gram-negative bacteria and some viruses.

[0043] 5. Polyglutamic acid is a naturally biodegradable polyamino acid that forms a soft hydrogel after cross-linking, reducing mechanical stimulation to tissues. The resulting composite material can be applied to the surface of a device using an adhesive to form a flexible antibacterial coating that can adapt to complex shapes.

[0044] 6. The cross-linking agent used is genipin, which, in addition to its cross-linking effect, also has the properties of anti-inflammatory and promoting collagen deposition, which can accelerate the healing of infected wounds.

[0045] 7. Silver nitrate and hydrogen peroxide form a strong oxidizing system under acidic conditions, which can selectively oxidize the hydroxyl groups or double bonds in the phospholipid molecules of liposomes to generate carboxyl groups, providing reaction sites for subsequent activation and grafting. In addition, the carboxylated surface can enhance the hydrophilicity of liposomes and improve their dispersibility in buffer solutions or hydrogels.

[0046] 8. EDC converts the carboxyl group into an active O-acylisourea intermediate, which is further converted by NHS into a more stable NHS ester, which is easier to react with the primary amines of PEI; PEI is a polyamine polymer rich in primary, secondary, and tertiary amine groups, which can bind to the activated carboxyl group through amide bonds, while forming a positively charged amino layer on the liposome surface.

[0047] 9. The amino groups of the amino liposomes can form amide bonds with the carboxyl groups of polyglutamic acid, so that the liposomes are firmly embedded in the hydrogel network, avoiding leakage, improving the stability of the composite material, and preventing the sudden release of liposomes during the use of the device.

[0048] 10. The positively charged amino groups of PEI can be adsorbed on the negatively charged bacterial membrane through electrostatic interaction, destroying the membrane integrity, producing a synergistic antibacterial effect with silver nanoparticles / quaternary ammonium salts, and expanding the antibacterial spectrum; the amino groups of PEI will be protonated at the infection site, enhancing hydrophilicity and accelerating the degradation of liposomes, and the release of antimicrobial agents triggered by the infection microenvironment. DETAILED DESCRIPTION

[0049] Unless otherwise specified, the reagents and instruments used in the following examples are commercially available products.

[0050] [Example 1]

[0051] A method for preparing a composite material for antibacterial nursing equipment comprises the following steps:

[0052] (1) Dissolve phospholipids in a chloroform-methanol mixed solvent, wherein the volume ratio of chloroform to methanol is 1:1, and 10 mL of the chloroform-methanol mixed solvent is used for every 100 mg of phospholipids; remove the solvent by rotary evaporation to form a lipid film, the rotary evaporation temperature is 30°C, the vacuum degree is 0.05 MPa, and the rotation speed is 100 rpm; disperse silver nanoparticles in phosphate buffer to obtain a mixed solution, wherein every 10 mg of silver nanoparticles is dispersed in 1 mL of buffer, and add the mixed solution to the dried lipid film, wherein the mass ratio of the dried lipid film to the silver nanoparticles is 3:1, and vortex for 5 minutes to form multilamellar liposomes;

[0053] (2) Dissolve polyglutamic acid and genipin in water, the mass ratio of polyglutamic acid to genipin is 5:1, and the mass ratio of polyglutamic acid to water is 10:1. Then add dimethyl sulfoxide dropwise and stir, the mass ratio of polyglutamic acid to dimethyl sulfoxide is 20:1. During the stirring process, add multilamellar liposomes, the mass ratio of polyglutamic acid to multilamellar liposomes is 5:1. Then slowly add catalyst EDC dropwise to carry out catalytic reaction, the mass ratio of catalyst to genipin is 1:1. After reacting for 20 hours, collect solid particles.

[0054] [Example 2]

[0055] A method for preparing a composite material for antibacterial nursing equipment comprises the following steps:

[0056] (1) Cholesterol was dissolved in a chloroform-methanol mixed solvent, wherein the volume ratio of chloroform to methanol was 4:1, and 30 mL of the chloroform-methanol mixed solvent was used for every 100 mg of cholesterol; the solvent was removed by rotary evaporation to form a lipid film, the rotary evaporation temperature was 50°C, the vacuum degree was 0.1 MPa, and the rotation speed was 60 rpm; benzalkonium chloride was dispersed in phosphate buffer to obtain a mixed solution, wherein 10 mg of benzalkonium chloride was dispersed in 10 mL of buffer, the mixed solution was added to the dried lipid film, the mass ratio of the dried lipid film to benzalkonium chloride was 8:1, and the mixture was vortexed for 10 minutes to form multilamellar liposomes;

[0057] (2) Dissolve polyglutamic acid and polyethylene glycol diglycidyl ether in water, the mass ratio of polyglutamic acid to polyethylene glycol diglycidyl ether is 10:1, and the mass ratio of polyglutamic acid to water is 5:1. Then, dimethyl sulfoxide is added dropwise and stirred, the mass ratio of polyglutamic acid to dimethyl sulfoxide is 100:1. During the stirring process, multilamellar liposomes are added, the mass ratio of polyglutamic acid to multilamellar liposomes is 2:1. Then, catalyst NHS is slowly added dropwise for catalytic reaction, the mass ratio of catalyst to polyethylene glycol diglycidyl ether is 3:1. After reacting for 10 hours, solid particles are collected.

[0058] [Example 3]

[0059] A method for preparing a composite material for antibacterial nursing equipment comprises the following steps:

[0060] (1) Phospholipids and cholesterol (mass ratio of 2:1) were dissolved in a chloroform-methanol mixed solvent, wherein the volume ratio of chloroform to methanol was 2:1, and 20 mL of the chloroform-methanol mixed solvent was used for every 100 mg of liposomes; the solvent was removed by rotary evaporation to form a lipid film, the rotary evaporation temperature was 40°C, the vacuum degree was 0.08 MPa, and the rotation speed was 80 rpm; hexadecyltrimethylammonium bromide was dispersed in phosphate buffer to obtain a mixed solution, wherein every 10 mg of hexadecyltrimethylammonium bromide was dispersed in 6 mL of buffer, and the mixed solution was added to the dried lipid film, wherein the mass ratio of the dried lipid film to hexadecyltrimethylammonium bromide was 5:1, and the mixture was vortexed for 8 minutes to form multilamellar liposomes;

[0061] (2) Polyglutamic acid and polyethylene glycol diglycidyl ether were dissolved in water, the mass ratio of polyglutamic acid to polyethylene glycol diglycidyl ether was 6:1, and the mass ratio of polyglutamic acid to water was 8:1. Dimethyl sulfoxide was then added dropwise and stirred, the mass ratio of polyglutamic acid to dimethyl sulfoxide was 50:1. Multilamellar liposomes were added during the stirring process, the mass ratio of polyglutamic acid to multilamellar liposomes was 4:1, and the catalyst EDC was slowly added dropwise for catalytic reaction, the mass ratio of catalyst to polyethylene glycol diglycidyl ether was 2:1. After the reaction was carried out for 15 hours, the solid particles were collected.

[0062] [Example 4]

[0063] A method for preparing a composite material for antibacterial nursing equipment comprises the following steps:

[0064] (1) Cholesterol was dissolved in a chloroform-methanol mixed solvent, wherein the volume ratio of chloroform to methanol was 2.5:1, and 25 mL of the chloroform-methanol mixed solvent was used for every 100 mg of cholesterol; the solvent was removed by rotary evaporation to form a lipid film, the rotary evaporation temperature was 35°C, the vacuum degree was 0.06 MPa, and the rotation speed was 70 rpm; silver nanoparticles and hexadecyltrimethylammonium bromide (mass ratio was 1:1) were dispersed in phosphate buffer to obtain a mixed solution, and every 10 mg of antibacterial substance was dispersed in 5 mL of buffer, and the mixed solution was added to the dried lipid film, and the mass ratio of the dried lipid film to the antibacterial substance was 6:1. The mixture was vortexed for 8 minutes to form multilamellar liposomes;

[0065] (2) Dissolve polyglutamic acid and genipin in water, the mass ratio of polyglutamic acid to genipin is 6:1, and the mass ratio of polyglutamic acid to water is 8:1. Then add dimethyl sulfoxide dropwise and stir, the mass ratio of polyglutamic acid to dimethyl sulfoxide is 50:1. During the stirring process, add multilamellar liposomes, the mass ratio of polyglutamic acid to multilamellar liposomes is 4:1. Then slowly add catalyst EDC dropwise to carry out catalytic reaction, the mass ratio of catalyst to genipin is 2:1. After the reaction for 15 hours, collect solid particles.

[0066] [Example 5]

[0067] A method for preparing a composite material for antibacterial nursing equipment comprises the following steps:

[0068] (1) Phospholipids and cholesterol (mass ratio of 2:1) were dissolved in a chloroform-methanol mixed solvent, wherein the volume ratio of chloroform to methanol was 2:1, and 20 mL of the chloroform-methanol mixed solvent was used for every 100 mg of liposomes; the solvent was removed by rotary evaporation to form a lipid film, the rotary evaporation temperature was 40°C, the vacuum degree was 0.08 MPa, and the rotation speed was 80 rpm; hexadecyltrimethylammonium bromide was dispersed in phosphate buffer to obtain a mixed solution, wherein every 10 mg of hexadecyltrimethylammonium bromide was dispersed in 6 mL of buffer, and the mixed solution was added to the dried lipid film, wherein the mass ratio of the dried lipid film to hexadecyltrimethylammonium bromide was 5:1, and the mixture was vortexed for 8 minutes to form multilamellar liposomes;

[0069] (2) The multilamellar vesicles were dispersed in an acetic acid solution with a pH of 5, with the mass ratio of the multilamellar vesicles to the acetic acid being 1:20. A 0.1 mol / L silver nitrate solution (the mass ratio of the silver nitrate to the multilamellar vesicles being 1:10) and a 5% hydrogen peroxide solution (the mass ratio of the hydrogen peroxide to the multilamellar vesicles being 1:30) were added under stirring. The mixture was placed in a 60°C water bath for 2 h. The precipitate was collected by centrifugation and dried to obtain the carboxylated multilamellar vesicles.

[0070] (3) The carboxylated multilamellar liposomes were dispersed in phosphate buffer at a mass ratio of 1:15, and EDC and NHS (molar ratio of 1:1) were added for activation for 50 min, with the sum of the mass of EDC and NHS accounting for 0.3% of the mass of the carboxylated multilamellar liposomes. Polyethyleneimine was added at a mass ratio of 1:1 to the carboxylated multilamellar liposomes, and the reaction was carried out at room temperature for 14 h. The precipitate was collected by centrifugation and dried at room temperature to obtain amino multilamellar liposomes.

[0071] (4) Polyglutamic acid and polyethylene glycol diglycidyl ether were dissolved in water, the mass ratio of polyglutamic acid to polyethylene glycol diglycidyl ether was 6:1, and the mass ratio of polyglutamic acid to water was 8:1. Dimethyl sulfoxide was then added dropwise and stirred, the mass ratio of polyglutamic acid to dimethyl sulfoxide was 50:1. Aminated multilamellar liposomes were added during the stirring process, the mass ratio of polyglutamic acid to the amino multilamellar liposomes was 4:1, and the catalyst EDC was slowly added dropwise for catalytic reaction, the mass ratio of the catalyst to polyethylene glycol diglycidyl ether was 2:1. After the reaction was carried out for 15 hours, the solid particles were collected.

[0072] [Example 6]

[0073] Step (1) and step (4) are the same as those in Example 5 and will not be repeated here. The only difference is steps (2) to (3), which are as follows:

[0074] (2) The multilamellar vesicles were dispersed in an acetic acid solution with a pH of 5, with a mass ratio of multilamellar vesicles to acetic acid of 1:30. A 0.3 mol / L silver nitrate solution (the mass ratio of silver nitrate to multilamellar vesicles was 1:15) and a 3% hydrogen peroxide solution (the mass ratio of hydrogen peroxide to multilamellar vesicles was 1:20) were added under stirring conditions. The mixture was placed in a 50°C water bath for 5 h. The precipitate was collected by centrifugation and dried to obtain carboxylated multilamellar vesicles.

[0075] (3) The carboxylated multilamellar liposomes were dispersed in phosphate buffer at a mass ratio of 1:30. EDC and NHS (molar ratio of 1:1.5) were added for activation for 20 min, and the sum of the mass of EDC and NHS accounted for 0.05% of the mass of the carboxylated multilamellar liposomes. Polyethyleneimine was added at a mass ratio of 1:2 to the carboxylated multilamellar liposomes. The reaction was carried out at room temperature for 8 h. The precipitate was collected by centrifugation and dried at room temperature to obtain amino multilamellar liposomes.

[0076] [Example 7]

[0077] Step (1) and step (4) are the same as those in Example 5 and will not be repeated here. The only difference is steps (2) to (3), which are as follows:

[0078] (2) The multilamellar vesicles were dispersed in an acetic acid solution with a pH of 5, with a mass ratio of multilamellar vesicles to acetic acid of 1:25. A 0.2 mol / L silver nitrate solution (the mass ratio of silver nitrate to multilamellar vesicles was 1:12) and a 4% hydrogen peroxide solution (the mass ratio of hydrogen peroxide to multilamellar vesicles was 1:25) were added under stirring. The mixture was placed in a 55°C water bath for 3 h. The precipitate was collected by centrifugation and dried to obtain carboxylated multilamellar vesicles.

[0079] (3) The carboxylated multilamellar liposomes were dispersed in phosphate buffer at a mass ratio of 1:20. EDC and NHS (molar ratio of 1:1.2) were added for activation for 30 min, and the sum of the mass of EDC and NHS accounted for 0.1% of the mass of the carboxylated multilamellar liposomes. Polyethyleneimine was added at a mass ratio of 1:1.5 to the carboxylated multilamellar liposomes. The reaction was carried out at room temperature for 10 h. The precipitate was collected by centrifugation and dried at room temperature to obtain amino multilamellar liposomes.

[0080] [Comparative Example 1]

[0081] A method for preparing a composite material for antibacterial nursing equipment comprises the following steps:

[0082] Polyglutamic acid and genipin were dissolved in water, the mass ratio of polyglutamic acid to genipin was 5:1, and the mass ratio of polyglutamic acid to water was 10:1. Dimethyl sulfoxide was then added dropwise with stirring, and the mass ratio of polyglutamic acid to dimethyl sulfoxide was 20:1. Silver nanoparticles were added during the stirring process (the amount added was the same as in Example 1), and then the catalyst EDC was slowly added dropwise for a catalytic reaction, and the mass ratio of the catalyst to genipin was 1:1. After reacting for 20 hours, solid particles were collected.

[0083] [Comparative Example 2]

[0084] The difference from Example 1 is that there is only step (1) and step (2) is missing.

[0085] A method for preparing a composite material for antibacterial nursing equipment comprises the following steps:

[0086] The phospholipids were dissolved in a chloroform-methanol mixed solvent, wherein the volume ratio of chloroform to methanol was 1:1, and 10 mL of the chloroform-methanol mixed solvent was used for every 100 mg of phospholipids; the solvent was removed by rotary evaporation to form a lipid film, the rotary evaporation temperature was 30°C, the vacuum degree was 0.05 MPa, and the rotation speed was 100 rpm; silver nanoparticles were dispersed in phosphate buffer to obtain a mixed solution, wherein every 10 mg of silver nanoparticles were dispersed in 1 mL of buffer, the mixed solution was added to the dried lipid film, the mass ratio of the dried lipid film to the silver nanoparticles was 3:1, and the film was vortexed for 5 minutes to form multilamellar liposomes.

[0087] [Comparative Example 3]

[0088] A method for preparing a composite material for antibacterial nursing equipment comprises the following steps:

[0089] Polyglutamic acid and genipin were dissolved in water, the mass ratio of polyglutamic acid to genipin was 5:1, and the mass ratio of polyglutamic acid to water was 10:1. Dimethyl sulfoxide was then added dropwise with stirring, and the mass ratio of polyglutamic acid to dimethyl sulfoxide was 20:1. During the stirring process, phospholipids and silver nanoparticles were added (the amount added was the same as in Example 1), and then the catalyst EDC was slowly added dropwise for a catalytic reaction, and the mass ratio of the catalyst to genipin was 1:1. After reacting for 20 hours, solid particles were collected.

[0090]

Characterization

[0091] 1. Antibacterial performance test

[0092] The antibacterial properties of the solid particles prepared in the examples and comparative examples were tested using the following method:

[0093] Staphylococcus aureus (ATCC6538) and Escherichia coli (ATCC25922) were selected, and the bacterial solution was prepared as follows: the bacteria were inoculated into NB medium, cultured at 37°C for 18-24 hours until the logarithmic growth phase (OD600 was 0.5), the bacteria were collected by centrifugation, washed twice with PBS, and resuspended to a concentration of 10 6 cfu / ml.

[0094] Experimental group: 10 mg of solid particles were mixed with 1 mL of bacterial solution and incubated at 37°C for 2 h. 9 mL of PBS was then added to dilute the mixture to terminate the antibacterial effect. 100 μL of the dilution was spread on a NA plate and cultured at 37°C for 24 h before counting the colonies (CFU).

[0095] Control group: 1 mL bacterial solution, PBS

[0096] Antibacterial rate (%) = 100% * (control group CFU - experimental group CFU) / control group CFU

[0097] 2. Antibacterial durability test

[0098] Accelerated aging treatment of solid particles: Soak the solid particles in a 37°C constant temperature water bath for 7 days to simulate long-term use. Sterile PBS was replaced daily to simulate liquid flushing. The antibacterial rate of the aged material was tested according to the antibacterial performance test method.

[0099]

[0100]

[0101] Analyze the data in the above table:

[0102] 1. The material prepared by the preparation method of the present application has excellent antibacterial properties and good antibacterial durability.

[0103] 2. From the data of Example 4, it can be seen that combining silver nanoparticles with quaternary ammonium salts can further improve the antibacterial properties of the material.

[0104] 3. From the data of Examples 5-7, it can be seen that amination treatment of multilamellar liposomes can further improve the antibacterial properties of the material.

[0105] Solid particles are dispersed in adhesives to obtain composite materials for antibacterial care devices. To demonstrate the experimental results, the following products are listed:

[0106] Product 1: The solid particles prepared in Example 3 were dispersed in bisphenol A epoxy resin. The mass ratio of solid particles to bisphenol A epoxy resin was 1:5. After mixing evenly, the material was coated on an aluminum plate at a coating amount of 0.2 g / dm 2 .

[0107] Product 2: The solid particles prepared in Example 4 were dispersed in an aqueous polyurethane emulsion with a mass ratio of solid particles to bisphenol A epoxy resin of 1:10. After mixing evenly, the material was coated on a stainless steel plate at a coating amount of 0.3 g / dm 2 .

[0108] Product 3: The solid particles prepared in Example 7 were dispersed in acrylic resin at a mass ratio of 1:6. After mixing evenly, the material was coated on a polyethylene sheet at a coating amount of 0.1 g / dm 2 .

[0109] Comparative product 1: The solid particles prepared in comparative example 1 were dispersed in bisphenol A epoxy resin. The mass ratio of solid particles to bisphenol A epoxy resin was 1:5. After mixing evenly, the material was coated on an aluminum plate at a coating amount of 0.2 g / dm 2 .

[0110] Comparative product 2: The solid particles prepared in comparative example 2 were dispersed in aqueous polyurethane emulsion, with a mass ratio of solid particles to bisphenol A epoxy resin of 1:10. After mixing evenly, the material was coated on a stainless steel plate at a coating amount of 0.3 g / dm 2 .

[0111] Comparative Product 3: The solid particles prepared in Comparative Example 3 were dispersed in acrylic resin. The mass ratio of solid particles to acrylic resin was 1:6. After mixing evenly, the material was coated on a polyethylene sheet at a coating amount of 0.1 g / dm 2 .

[0112] The product was characterized as follows:

[0113] 1. Adhesion test: Test according to the method of standard GB / T 9286-2021;

[0114] 2. Antibacterial rate test: The antibacterial rate test was carried out according to the method of standard GB / T 21866-2008, and the test bacteria was Staphylococcus aureus.

[0115] Product Number Adhesion / Grade Antibacterial rate% Product 1 0 94.8 Product 2 0 97.2 Product 3 0 99.5 Comparison product 1 2 68.5 Comparison Product 2 2 30.8 Comparison product 3 2 65.2

[0116] Analyze the data in the above table:

[0117] The composite material prepared in this application is coated on common antibacterial care equipment materials, and has very good adhesion without the phenomenon of particle shedding; and the solid particles are dispersed in the adhesive, and experimental inflammation has shown that there is no adverse effect on the antibacterial rate.

[0118] The various embodiments in this specification are described in a progressive manner. Similar parts between the various embodiments can be referred to in conjunction with each other. Each embodiment focuses on the differences between the other embodiments. In particular, the system embodiments are generally similar to the method embodiments, so the description is relatively simple. For relevant parts, refer to the description of the method embodiments.

[0119] The foregoing is merely an embodiment of the present application and is not intended to limit the present application. For those skilled in the art, the present application may have various changes and variations. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present application should all be included within the scope of the claims of the present application.

Claims

1. A method for preparing a composite material for antibacterial nursing equipment, characterized in that: The steps include: (1) dissolving liposomes in a chloroform-methanol mixed solvent, removing the solvent by rotary evaporation to form a lipid film, dispersing the antibacterial substance in a buffer solution to obtain a mixed solution, adding the mixed solution to the dried lipid film, and vortexing to form multilamellar liposomes; (2) Dissolving polyglutamic acid and a cross-linking agent in water, then adding dimethyl sulfoxide dropwise and stirring, adding multilamellar liposomes during the stirring process, then slowly adding a catalyst dropwise to carry out a catalytic reaction, and collecting solid particles after the reaction; dispersing the solid particles in an adhesive to obtain a composite material for antibacterial nursing devices.

2. A preparation method according to claim 1, characterized in that: In step (1), the liposomes are phospholipids and / or cholesterol; The antibacterial substance is silver nanoparticles and / or quaternary ammonium salt, and the quaternary ammonium salt is benzalkonium chloride and / or cetyltrimethylammonium bromide.

3. A preparation method according to claim 1, characterized in that: The mass ratio of the dried lipid film to the antibacterial substance is (3-8):

1.

4. A preparation method according to claim 1, characterized in that: The cross-linking agent in step (2) is genipin or polyethylene glycol diglycidyl ether; The catalyst is 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride or N-hydroxysuccinimide.

5. A preparation method according to claim 1, characterized in that: The mass ratio of the polyglutamic acid to the cross-linking agent is (5-10):1; The mass ratio of the polyglutamic acid to the multilamellar liposome is (2-5):1; The mass ratio of the catalyst to the cross-linking agent is (1-3):

1.

6. A preparation method according to claim 1, characterized in that: The adhesive is one or more of gelatin, sodium alginate, polyurethane, epoxy resin, polylactic acid-glycolic acid copolymer, and acrylic resin; The mass ratio of the solid particles to the adhesive is 1:(5-10).

7. A preparation method according to claim 1, characterized in that: The multilamellar liposomes obtained in step (1) are subjected to an amination treatment, the steps being: S1. Dispersing the multilamellar liposomes in an acetic acid solution with a pH of 5, adding a silver nitrate solution and a hydrogen peroxide solution under stirring, placing the solution in a water bath at 50-60° C. for 2-5 hours, collecting the precipitate by centrifugation, and drying the solution to obtain the carboxylated multilamellar liposomes; S2. The carboxylated multilamellar liposomes obtained in step S1 are dispersed in phosphate buffer, and activated by adding 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide for 20-50 min; polyethyleneimine is added, and the reaction is carried out at room temperature for 8-14 h. The precipitate is collected by centrifugation and dried at room temperature to obtain amino multilamellar liposomes.

8. A preparation method according to claim 7, characterized in that: The concentration of the silver nitrate solution is 0.1-0.3 mol / L, and the mass ratio of silver nitrate to multilamellar liposome is 1:(10-15); The mass fraction of hydrogen peroxide in the hydrogen peroxide solution is 3-5%, and the mass ratio of hydrogen peroxide to multilamellar liposome is 1:(20-30).

9. A preparation method according to claim 7, characterized in that: The molar ratio of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride to N-hydroxysuccinimide is 1:(1-1.5); The sum of the mass of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide accounts for 0.05-0.3% of the mass of the carboxylated multilamellar liposomes; The mass ratio of polyethyleneimine to carboxylated multilamellar vesicles was 1:(1-2).

10. A composite material for antibacterial nursing devices prepared according to any one of claims 1 to 9, characterized in that: Used in wound dressings, medical bandages, tissue engineering scaffolds, medical device coatings, indwelling catheters or sutures.

Images