CN116473997B - Hypochlorous acid disinfectant and preparation method thereof - Google Patents

Hypochlorous acid disinfectant and preparation method thereof Download PDF

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CN116473997B
CN116473997B CN202310736606.0A CN202310736606A CN116473997B CN 116473997 B CN116473997 B CN 116473997B CN 202310736606 A CN202310736606 A CN 202310736606A CN 116473997 B CN116473997 B CN 116473997B
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hypochlorous acid
disinfectant
antibiotic
polysaccharide
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CN116473997A (en
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李晓奉
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Guangzhou Jinglangyuan Environmental Protection Technology Co ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/20Elemental chlorine; Inorganic compounds releasing chlorine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/351Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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    • A61K31/65Tetracyclines
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716Glucans
    • A61K31/717Celluloses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716Glucans
    • A61K31/722Chitin, chitosan
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/74Synthetic polymeric materials
    • A61K31/785Polymers containing nitrogen
    • A61K31/787Polymers containing nitrogen containing heterocyclic rings having nitrogen as a ring hetero atom
    • A61K31/79Polymers of vinyl pyrrolidone
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    • A61K38/00Medicinal preparations containing peptides
    • A61K38/04Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/14Peptides containing saccharide radicals; Derivatives thereof, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0014Skin, i.e. galenical aspects of topical compositions
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/02Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/02Local antiseptics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10Antimycotics
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    • C25B1/00Electrolytic production of inorganic compounds or non-metals
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    • C25B11/073Electrodes formed of electrocatalysts on a substrate or carrier characterised by the electrocatalyst material
    • C25B11/091Electrodes formed of electrocatalysts on a substrate or carrier characterised by the electrocatalyst material consisting of at least one catalytic element and at least one catalytic compound; consisting of two or more catalytic elements or catalytic compounds
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention discloses hypochlorous acid disinfectant and a preparation method thereof, and relates to the technical field of disinfectant, wherein the disinfectant comprises the following components in parts by weight: 2-6 parts of hypochlorous acid, 10-15 parts of polysaccharide antibiotic compound, 2-6 parts of pyridinium bromide, 4-9 parts of stabilizer, 1-4 parts of neutralizer, 12-17 parts of surfactant and 65-80 parts of deionized water. The concentration of available chlorine in the product is 400-800 ppm, the pH value of the whole solution of the disinfectant is kept 5-6, pyridinium bromide is sterilized by being matched with hypochlorous acid, and the polysaccharide antibiotic component is added, so that the stimulation to wound surfaces of wounds can be reduced, pathogens and bacteria are eliminated, the skin permeability of the ointment is increased, the medicine is permeated into the dermis of the skin to perform treatment and auxiliary hypochlorous acid deep sterilization, the effect of promoting is achieved, and the disinfectant is suitable for sterilizing skin wounds with high erosion degrees such as operation, skin diseases and burn.

Description

Hypochlorous acid disinfectant and preparation method thereof
Technical Field
The invention relates to the technical field of disinfectant, in particular to hypochlorous acid disinfectant and a preparation method thereof.
Background
Sodium hypochlorite is a strong electrolyte, firstly ionizes in water to generate hypochlorite ions, and if the hypochlorite ions hydrolyze, hypochlorous acid can be generated, the hypochlorite ions are further decomposed to generate nascent oxygen, and the nascent oxygen has very active chemical property and very strong oxidizing power and plays a great role in the disinfection process. The disinfection principle of the hypochlorous acid disinfectant is that hypochlorous acid is subjected to oxidation-reduction action with bacterial cell walls and virus shells to crack germs; because of unstable decomposition to generate nascent oxygen, the extremely strong oxidizing property of the nascent oxygen denatures the proteins of thalli and viruses, thereby killing pathogenic microorganisms; chloride ions can significantly alter the osmotic pressure of bacteria and virions, resulting in their loss of activity and death.
Antibiotics have been the primary drug to treat bacterial infections since the discovery of penicillin in the 40 th century. With the widespread use of antibiotics, drug-resistant strains have become pathogenic bacteria which are common in clinical infections, and the generation and increasing of multi-drug resistance phenomenon make the treatment of bacterial infections very challenging. For infection caused by intracellular bacteria, antibiotics must first bind to target pathogenic bacteria in the cell to act, and thus the antibacterial effect of the antibiotics is affected by many factors, including the concentration, distribution and duration of action of the antibiotics in the cell. Therefore, the method carries out certain chemical modification on the antibiotics, optimizes the intracellular pharmacokinetic parameters of the antibiotics, and has great significance for expanding the application of the existing antibiotics in the treatment of infection caused by intracellular bacteria.
Publication number CN108079017B discloses a hypochlorous acid wound disinfectant containing antibacterial polysaccharide compounds or derivatives, which has good sterilizing effect and long duration, but the product of the invention is only used for superficial wound disinfection, is not suitable for skin wound surfaces with higher erosion degree, has poor skin permeability of medicines, and cannot deeply sterilize and assist in medicine treatment.
Disclosure of Invention
The invention aims to solve the technical problems and needs, and discloses hypochlorous acid disinfectant which is higher in available chlorine content, stronger in sterilization effect, capable of increasing skin permeability of ointment, capable of promoting medicine penetration into dermis of skin for treatment and assisting hypochlorous acid deep sterilization, and suitable for disinfecting skin wounds with higher erosion degrees such as surgery, skin diseases and burns.
The invention adopts the following technical scheme:
the hypochlorous acid disinfectant comprises the following components in parts by weight: 2-6 parts of hypochlorous acid, 10-15 parts of polysaccharide antibiotic compound, 2-6 parts of pyridinium bromide, 5-9 parts of polyvinylpyrrolidone, 4-9 parts of stabilizer, 1-4 parts of neutralizer, 12-17 parts of surfactant and 65-80 parts of deionized water.
Preferably, the disinfectant comprises the following components in parts by weight: 3-5 parts of hypochlorous acid, 11-14 parts of polysaccharide antibiotic compound, 2-4 parts of pyridinium bromide, 6-8 parts of polyvinylpyrrolidone, 6-8 parts of stabilizer, 1-3 parts of neutralizer, 13-16 parts of surfactant and 68-73 parts of deionized water.
Preferably, the disinfectant comprises the following components in parts by weight: 4 parts of hypochlorous acid, 12 parts of polysaccharide antibiotic compound, 3 parts of pyridinium bromide, 7 parts of polyvinylpyrrolidone, 7 parts of stabilizer, 2 parts of neutralizer, 15 parts of surfactant and 70 parts of deionized water.
Preferably, the concentration of available chlorine in the disinfectant is 400-800 ppm, and the pH value of the whole disinfectant solution is kept to be 5-6.
Preferably, the pyridine ammonium bromide is selected from one of cetyl pyridine ammonium bromide, dodecyl pyridine ammonium bromide, tetradecyl-2-methyl pyridine ammonium bromide, n-butyl pyridine ammonium bromide, more preferably tetradecyl-2-methyl pyridine ammonium bromide. The tetradecyl-2-methylpyridine ammonium bromide is an electrolyte, and the external groups can ionize water and can be used in an electrolysis system of a nano material together with polyvinylpyrrolidone.
Preferably, the hypochlorous acid preparation method comprises the following steps:
s1, pretreating an anode of an electrolytic cell, adding a carbon nano tube into propylene glycol, performing ultrasonic treatment for 30 minutes, coating an electrode reaction catalyst on the anode, and roasting at 200-300 ℃ for 30 minutes to finish the treatment;
s2, introducing 0.1-0.2wt% of sodium chloride or potassium chloride solution into the cathode chamber and the anode chamber, connecting with a power supply of an electrolytic tank, and carrying out electrolysis to obtain hypochlorous acid.
Preferably, the electrode reaction catalyst is a mixture of platinum dioxide and tin tetrachloride in a mass ratio of 3:1.
Preferably, the coating amount of the electrode reaction catalyst on the anode is 8-10 g/m 2
According to the invention, the anode is coated with the catalyst to form the rugged honeycomb coating on the surface of the anode, so that the number of active points on the surface of the anode is increased, the electrochemical activity of the anode is improved, the carbon nano tube provides attachment points for platinum and tin, finer grains are promoted to be obtained, the hypochlorous acid produced by the electrode under the condition of low energy consumption can release stable high-concentration available chlorine, the sterilization and disinfection capability is stronger, and the synergistic sterilization with the polysaccharide antibiotics is facilitated.
Preferably, the preparation method of the polysaccharide antibiotic complex comprises the following steps:
s11, preparing chitosan and antibiotic aqueous solution, wherein the molar ratio of chitosan to antibiotic to deionized water is (1:3) - (5): 10-15, adding sodium cyanoborohydride accounting for 20-30% of the mass of the antibiotic, stirring at room temperature in a dark place, and reacting at 90-100 ℃ for 8-12 h;
s12, transferring the aqueous solution obtained in the step S11 into a 3kDa dialysis bag for dialysis for 2-3 d to obtain a dialysate;
s13, dissolving cellulose in deionized water with the mass of 2 times that of the cellulose, mixing a cellulose aqueous solution and a dialyzate under a stirring condition, and continuously stirring for 2-3 hours at the temperature of 30-40 ℃;
s14, carrying out vacuum freeze drying on the mixed solution obtained in the step S13 for 36-48 hours, wherein the temperature is-30 to-50 ℃, and the vacuum degree is 20-30 Pa, so as to obtain the polysaccharide antibiotic compound.
Preferably, the molecular weight cut-off of the dialysis bag is 3000-7000.
Preferably, the chitosan is carboxymethyl chitosan with a deacetylation degree of more than 80%;
preferably, the cellulose is hydroxypropyl cellulose or sodium carboxymethyl cellulose;
preferably, the antibiotic is one of vancomycin, tetracycline, la Sha Junsu and monensin.
Preferably, the stabilizer comprises one or more of disodium ethylenediamine tetraacetate, sodium silicate and sodium phosphate.
Preferably, the neutralizer is a PBS solution containing 0.5-1wt% of sodium thiosulfate, 0.5-1wt% of lecithin and 1-2wt% of Tween 60.
The chitosan, cellulose and antibiotic compound is added, so that the antibacterial disinfectant has good biocompatibility and excellent film forming performance, is sprayed on the surface of a severe skin erosion wound when being used for medical disinfectant, acts on pathogen or bacterial cell membranes remained on the dermis layer of the skin to cause perforation and destroy ion channels of the pathogen, finally leads to autolysis and death of thalli, can form an antibacterial and bacteriostatic breathable film on the surface of the skin, has a blocking effect on external bacteria, can reduce the stimulation of hypochlorous acid on the skin, and helps to realize drug permeation treatment.
Preferably, the surfactant comprises by weight: 2-8 parts of fatty alcohol polyoxyethylene ether, 3-7 parts of sodium dodecyl diphenyl ether disulfonate, 1-4 parts of sodium hexametaphosphate, 8-12 parts of alkylphenol polyoxyethylene and 5-10 parts of nonylphenol polyoxyethylene.
Preferably, the preparation method of the disinfectant comprises the following steps:
dissolving pyridinium bromide, polyvinylpyrrolidone and hypochlorous acid in deionized water, adding into a vacuum emulsification stirrer, vacuumizing and stirring for 30min; slowly adding a stabilizer and a neutralizer, stirring while adding, and adjusting the pH value to 5.5-6; and adding the polysaccharide antibiotic compound, stirring for 20-30 min at 30-35 ℃, slowly adding the surfactant, and stirring for 10-20 min to obtain the hypochlorous acid disinfectant.
The hypochlorous acid disinfectant is applied to medical disinfection, and is particularly applied to pre-drug disinfection or daily disinfection of surgical wound surfaces, burn wound surfaces, acne ulcer wound surfaces and various skin disease wound surfaces with higher erosion degree; the skin diseases include, but are not limited to, AIDS, syphilis, herpes zoster or herpes simplex, erythema scale skin diseases, acute suppurative skin diseases caused by fungal or bacterial infections.
The invention has the beneficial effects that:
the hypochlorous acid disinfectant disclosed by the invention uses pyridinium bromide and polyvinylpyrrolidone to be matched with hypochlorous acid for sterilization, so that the duration of the sterilizing effect of the hypochlorous acid on wound surfaces is prolonged.
The disinfectant disclosed by the invention is introduced with chitosan, cellulose and antibiotic compound, can kill pathogens, has an antibacterial effect, good biocompatibility and excellent film forming performance, is sprayed on the surface of a severe skin erosion wound when being used for medical disinfection, acts on the cell membrane of pathogens or bacteria which are retained in the dermis of the skin, causes perforation, damages the ion channel of the pathogens, and finally causes autolysis of thalli to die. The antibacterial and bacteriostatic breathable film can be formed on the surface of the skin, so that the antibacterial and bacteriostatic breathable film has a blocking effect on external bacteria, the skin permeability of the ointment is increased, and the antibacterial and bacteriostatic ointment has a promoting effect on the treatment of drug permeation into the dermis of the skin and the auxiliary hypochlorous acid deep sterilization.
According to the invention, the anode of the electrolytic tank for producing hypochlorous acid is coated with the catalyst, the rugged honeycomb coating is formed on the surface of the anode, the number of active points on the surface of the anode is increased, the electrochemical activity of the anode is improved, the carbon nano tube provides attachment points for platinum and tin, finer grains are promoted to be obtained, the hypochlorous acid produced by the electrode under the condition of low energy consumption can release stable high-concentration available chlorine, the sterilizing capacity is more efficient, and the synergistic sterilization with polysaccharide antibiotics is facilitated.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and fully with reference to the accompanying drawings, in which it is evident that the embodiments described are only some, but not all embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Example 1.
The hypochlorous acid disinfectant of the embodiment comprises the following components in parts by weight: 2 parts of hypochlorous acid, 10 parts of polysaccharide antibiotic compound, 2 parts of pyridinium bromide, 5 parts of polyvinylpyrrolidone, 4 parts of stabilizer, 1 part of neutralizer, 12 parts of surfactant and 65 parts of deionized water.
The concentration of available chlorine in the disinfectant of this example was 400ppm, and the pH of the entire solution of the disinfectant was maintained at 5.
The hypochlorous acid preparation method of the embodiment comprises the following steps:
s1, pretreating an anode of an electrolytic cell, adding a carbon nano tube into propylene glycol, performing ultrasonic treatment for 30min, coating an electrode reaction catalyst on the anode, and roasting at 200 ℃ for 30min to finish the treatment;
s2, introducing 0.1wt% of sodium chloride or potassium chloride solution into the cathode chamber and the anode chamber, and connecting with a power supply of an electrolytic tank to electrolyze to obtain hypochlorous acid.
The electrode reaction catalyst of this example was a mixture of platinum dioxide and tin tetrachloride in a mass ratio of 3:1.
The coating amount of the electrode reaction catalyst on the anode of this example was 8g/m 2
The preparation method of the polysaccharide antibiotic complex of the embodiment comprises the following steps:
s11, preparing chitosan and antibiotic aqueous solution, wherein the molar ratio of chitosan to antibiotic to deionized water is 1:3:10, adding 20% of cyano sodium borohydride by mass of antibiotics, stirring at room temperature in a dark place, and reacting at 90 ℃ for 8 hours;
s12, transferring the aqueous solution obtained in the step S11 into a 3kDa dialysis bag for dialysis for 2d to obtain dialysate;
s13, dissolving cellulose in deionized water with the mass of 2 times of that of the cellulose, mixing the cellulose aqueous solution and the dialyzate under the stirring condition, and continuously stirring for 2 hours at 30 ℃;
s14, carrying out vacuum freeze drying on the mixed solution obtained in the step S13 for 36 hours, wherein the temperature is-30 ℃ and the vacuum degree is 20Pa, and thus the polysaccharide antibiotic compound is obtained.
The dialysis bag of this example has a molecular weight cut-off of 3000.
The chitosan of the embodiment is carboxymethyl chitosan with the deacetylation degree of more than 80 percent;
the cellulose of this example is hydroxypropyl cellulose;
the antibiotic of this example is vancomycin.
The stabilizer of this example was disodium ethylenediamine tetraacetate.
The neutralizing agent of this example was a PBS solution containing 0.5wt% sodium thiosulfate, 0.5wt% lecithin, and 1wt% Tween 60.
The surfactant of this embodiment comprises, in parts by weight: 2 parts of fatty alcohol polyoxyethylene ether, 3 parts of sodium dodecyl diphenyl ether disulfonate, 1 part of sodium hexametaphosphate, 8 parts of alkylphenol polyoxyethylene and 5 parts of nonylphenol polyoxyethylene.
The preparation method of the disinfectant of the embodiment comprises the following steps:
dissolving pyridinium bromide, polyvinylpyrrolidone and hypochlorous acid in deionized water, adding into a vacuum emulsification stirrer, vacuumizing and stirring for 30min; slowly adding a stabilizer and a neutralizer, stirring while adding, and regulating the pH value to be 5; adding the polysaccharide antibiotic compound, stirring at 30deg.C for 20min, slowly adding surfactant, and stirring for 10min to obtain hypochlorous acid disinfectant.
Example 2.
The hypochlorous acid disinfectant of the embodiment comprises the following components in parts by weight: 6 parts of hypochlorous acid, 15 parts of polysaccharide antibiotic compound, 2-6 parts of pyridinium bromide, 9 parts of polyvinylpyrrolidone, 9 parts of stabilizer, 4 parts of neutralizer, 17 parts of surfactant and 80 parts of deionized water.
The concentration of available chlorine in the disinfectant in this example was 800ppm, and the pH value of the entire disinfectant solution was maintained at 6.
The hypochlorous acid preparation method of the embodiment comprises the following steps:
s1, pretreating an anode of an electrolytic cell, adding a carbon nano tube into propylene glycol, performing ultrasonic treatment for 30 minutes, coating an electrode reaction catalyst on the anode, and roasting at 300 ℃ for 30 minutes to finish the treatment;
s2, introducing 0.2wt% of sodium chloride or potassium chloride solution into the cathode chamber and the anode chamber, and connecting with a power supply of an electrolytic tank to electrolyze to obtain hypochlorous acid.
The electrode reaction catalyst of this example was a mixture of platinum dioxide and tin tetrachloride in a mass ratio of 3:1.
The coating amount of the electrode reaction catalyst on the anode of this example was 10g/m 2
The preparation method of the polysaccharide antibiotic complex of the embodiment comprises the following steps:
s11, preparing chitosan and antibiotic aqueous solution, wherein the molar ratio of chitosan to antibiotic to deionized water is 1:5:15, adding 30% of cyano sodium borohydride by mass of antibiotics, stirring at room temperature in a dark place, and reacting at 100 ℃ for 12 hours;
s12, transferring the aqueous solution obtained in the step S11 into a 3kDa dialysis bag for dialysis for 3d to obtain a dialysate;
s13, dissolving cellulose in deionized water with the mass of 2 times of that of the cellulose, mixing the cellulose aqueous solution and the dialyzate under the stirring condition, and continuously stirring for 3 hours at 40 ℃;
s14, carrying out vacuum freeze drying on the mixed solution obtained in the step S13 for 48 hours at the temperature of 50 ℃ below zero and the vacuum degree of 30Pa, thus obtaining the polysaccharide antibiotic compound.
The dialysis bag of this example had a molecular weight cut-off of 7000.
The chitosan of the embodiment is carboxymethyl chitosan with the deacetylation degree of more than 80 percent;
the cellulose of this example is sodium carboxymethyl cellulose;
the antibiotic of this example is monensin.
The stabilizer of this example is sodium phosphate.
The neutralizing agent of this example was a PBS solution containing 1wt% sodium thiosulfate, 1wt% lecithin, and 2wt% Tween 60.
The surfactant of this example comprises by weight: 8 parts of fatty alcohol polyoxyethylene ether, 7 parts of sodium dodecyl diphenyl ether disulfonate, 4 parts of sodium hexametaphosphate, 12 parts of alkylphenol polyoxyethylene and 10 parts of nonylphenol polyoxyethylene.
The preparation method of the disinfectant of the embodiment comprises the following steps:
dissolving pyridinium bromide, polyvinylpyrrolidone and hypochlorous acid in deionized water, adding into a vacuum emulsification stirrer, vacuumizing and stirring for 30min; slowly adding a stabilizer and a neutralizer, stirring while adding, and regulating the pH value to be 6; adding the polysaccharide antibiotic compound, stirring at 35deg.C for 30min, slowly adding surfactant, and stirring for 20min to obtain hypochlorous acid disinfectant.
Example 3.
The hypochlorous acid disinfectant of the embodiment comprises the following components in parts by weight: 4 parts of hypochlorous acid, 12 parts of polysaccharide antibiotic compound, 3 parts of pyridinium bromide, 7 parts of polyvinylpyrrolidone, 7 parts of stabilizer, 2 parts of neutralizer, 15 parts of surfactant and 70 parts of deionized water.
The concentration of available chlorine in the disinfectant of this example was 600ppm, and the pH of the entire solution of the disinfectant was maintained at 5.5.
The hypochlorous acid preparation method of the embodiment comprises the following steps:
s1, pretreating an anode of an electrolytic cell, adding a carbon nano tube into propylene glycol, performing ultrasonic treatment for 30 minutes, coating an electrode reaction catalyst on the anode, and roasting at 250 ℃ for 30 minutes to finish the treatment;
s2, introducing 0.15wt% of sodium chloride or potassium chloride solution into the cathode chamber and the anode chamber, and connecting with a power supply of an electrolytic tank to electrolyze to obtain hypochlorous acid.
The electrode reaction catalyst of this example was a mixture of platinum dioxide and tin tetrachloride in a mass ratio of 3:1.
The coating amount of the electrode reaction catalyst on the anode of this example was 9g/m 2
The preparation method of the polysaccharide antibiotic complex of the embodiment comprises the following steps:
s11, preparing chitosan and antibiotic aqueous solution, wherein the molar ratio of chitosan to antibiotic to deionized water is 1:4:13, adding sodium cyanoborohydride accounting for 25% of the mass of the antibiotic, stirring at room temperature in a dark place, and reacting at 95 ℃ for 10 hours;
s12, transferring the aqueous solution obtained in the step S11 into a 3kDa dialysis bag for dialysis for 2.5d to obtain a dialysate;
s13, dissolving cellulose in deionized water with the mass of 2 times of that of the cellulose, mixing the cellulose aqueous solution and the dialyzate under the stirring condition, and continuously stirring for 2.5 hours at 35 ℃;
s14, carrying out vacuum freeze drying on the mixed solution obtained in the step S13 for 42h, wherein the temperature is-40 ℃ and the vacuum degree is 30Pa, and thus the polysaccharide antibiotic compound is obtained.
The dialysis bag of this example has a molecular weight cut-off of 5000.
The chitosan of the embodiment is carboxymethyl chitosan with the deacetylation degree of more than 80 percent;
the cellulose of this example is hydroxypropyl cellulose;
the antibiotic of this example is La Sha Junsu.
The stabilizer of this example is sodium silicate.
The neutralizing agent of this example was a PBS solution containing 0.8wt% sodium thiosulfate, 0.7wt% lecithin, and 1.5wt% Tween 60.
The surfactant of this example comprises by weight: 5 parts of fatty alcohol polyoxyethylene ether, 5 parts of sodium dodecyl diphenyl ether disulfonate, 2 parts of sodium hexametaphosphate, 10 parts of alkylphenol polyoxyethylene and 8 parts of nonylphenol polyoxyethylene.
The preparation method of the disinfectant of the embodiment comprises the following steps:
dissolving pyridinium bromide, polyvinylpyrrolidone and hypochlorous acid in deionized water, adding into a vacuum emulsification stirrer, vacuumizing and stirring for 30min; slowly adding a stabilizer and a neutralizer, stirring while adding, and regulating the pH value to 5.5; adding the polysaccharide antibiotic compound, stirring at 30deg.C for 25min, slowly adding surfactant, and stirring for 15min to obtain hypochlorous acid disinfectant.
Comparative example 1.
The difference from example 3 is that no polysaccharide antibiotic complex is added.
Comparative example 2.
Unlike example 3, polyvinylpyrrolidone was not added.
Comparative example 3.
Unlike example 3, the pyridinium bromide was replaced with benzalkonium bromide.
Comparative example 4.
Unlike example 3, the electrode catalyst was Raney-Ni.
Comparative example 5.
The difference from example 3 is that the cellulose in the polysaccharide antibiotic complex is replaced with starch and the chitosan is replaced with bovine serum albumin.
Comparative example 6.
The antibiotic which is the polysaccharide antibiotic complex is penicillin, unlike example 3.
Comparative example 7.
Unlike example 3, the polysaccharide antibiotic complex was prepared by the following method:
s11, respectively dissolving chitosan and cellulose in water, respectively adding sodium borohydride accounting for 50% of the mass of the antibiotics, respectively stirring uniformly, then mixing the chitosan aqueous solution and the cellulose aqueous solution, adding the antibiotics, and stirring for 30min at room temperature in a dark place;
s12, transferring the mixed solution obtained in the step S11 into a dialysis bag with the molecular weight cut-off of 15000 for dialysis for 1d to obtain a dialysate;
and S13, carrying out infrared drying on the dialysate obtained in the step S12 to obtain the polysaccharide antibiotic compound.
The chitosan of the embodiment is carboxymethyl chitosan with the deacetylation degree of more than 80 percent;
the cellulose of this example is sodium carboxymethyl cellulose;
the antibiotic of this example is La Sha Junsu.
1. Sterilization test
Experimental strain: coli, staphylococcus aureus, listeria, candida albicans, pseudomonas aeruginosa, and beta-hemolytic streptococcus.
The 12-hour liquid cultures of the above bacteria were divided into 6 groups, each group containing 10 strain culture samples, the test was performed using the sterilizing solutions of examples 1-3 and comparative examples 1-7, respectively, uniformly coated on the surfaces of common plates with sterile swabs, slightly dried, and the drug-sensitive paper sheets having the sterilizing solutions of examples 1-3 and comparative examples 1-7 absorbed therein were held by sterile forceps, spread on the surfaces of the above bacteria-inoculated plates, one plate was placed with 3 drug-sensitive paper sheets, incubated at 35℃for 30 minutes, and the results were observed and recorded.
Sterilization rate= (average number of bacteria of sample before sterilization-average number of bacteria of sample after sterilization)/average number of bacteria of sample before sterilization.
The test results are shown in Table 1:
2. skin penetration test
The Franz diffusion cell system was used as a device for transdermal permeation testing using a phosphate buffer solution containing 0.5% sodium azide, which was maintained at 30℃and stirred at 500rpm during the test. The hypochlorous acid disinfectant solutions of examples 1-3 and comparative examples 1-7 were sprayed on skin samples of mice comprising epidermis layer and dermis layer, and after 5min, the ointment was uniformly applied, and then the skin samples of mice were placed in a Franz diffusion cell system.
Samples were collected and analyzed by HPLC to determine the 24 hour cumulative penetration (μg/cm) of the ointment 2 ) Cumulative permeation (%) relative to the initial content and skin permeation (μg/cm) 2 /h)。
The test results are shown in Table 2:
according to the test, chitosan, cellulose and antibiotic compound are introduced into the disinfectant, so that the disinfectant can kill pathogens, has an antibacterial effect, good biocompatibility and excellent film forming performance, is sprayed on the surface of a severe skin erosion wound when being used for medical disinfection, acts on the pathogens or bacterial cell membranes which are retained in dermis layers of the skin, causes perforation, damages ion channels of the pathogens, and finally leads to autolysis of the thalli to die. The antibacterial and bacteriostatic breathable film can be formed on the surface of the skin, so that the antibacterial and bacteriostatic breathable film has a blocking effect on external bacteria, the irritation of hypochlorous acid to the skin is reduced, the skin permeability of the ointment is increased, and the antibacterial and bacteriostatic breathable film has a promoting effect on the treatment of drug penetration into the dermis of the skin and the auxiliary hypochlorous acid deep sterilization.
The anode of the electrolytic tank for producing hypochlorous acid is coated with a catalyst, so that an uneven honeycomb coating is formed on the surface of the anode, the number of active electrons on the surface of the anode is increased, the electrochemical activity of the anode is improved, and carbon nanotubes provide attachment points for platinum and tin to promote finer grains, so that the hypochlorous acid produced by the electrode under the condition of low energy consumption can release stable high-concentration available chlorine, and the coordination efficiency with polysaccharide antibiotics is higher.
It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative embodiments, and that the present invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.
Furthermore, it should be understood that although the present disclosure describes embodiments, not every embodiment is provided with a separate embodiment, and that this description is provided for clarity only, and that the disclosure is not limited to the embodiments described in detail below, and that the embodiments described in the examples may be combined as appropriate to form other embodiments that will be apparent to those skilled in the art.

Claims (5)

1. The hypochlorous acid disinfectant is characterized by comprising the following components in parts by weight: 2-6 parts of hypochlorous acid, 10-15 parts of polysaccharide antibiotic compound, 2-6 parts of pyridinium bromide, 5-9 parts of polyvinylpyrrolidone, 4-9 parts of stabilizer, 1-4 parts of neutralizer, 12-17 parts of surfactant and 65-80 parts of deionized water;
the preparation method of the polysaccharide antibiotic compound comprises the following steps:
s11, preparing chitosan and antibiotic aqueous solution, wherein the molar ratio of chitosan to antibiotic to deionized water is (1:3) - (5): 10-15, adding sodium cyanoborohydride accounting for 20-30% of the mass of the antibiotic, stirring at room temperature in a dark place, and reacting at 90-100 ℃ for 8-12 h;
s12, transferring the aqueous solution obtained in the step S11 into a 3kDa dialysis bag for dialysis for 2-3 d to obtain a dialysate;
s13, dissolving cellulose in deionized water with the mass of 2 times that of the cellulose, mixing a cellulose aqueous solution and a dialyzate under a stirring condition, and continuously stirring for 2-3 hours at the temperature of 30-40 ℃;
s14, carrying out vacuum freeze drying on the mixed solution obtained in the step S13 for 36-48 hours at the temperature of minus 30 to minus 50 ℃ and the vacuum degree of 20-30 Pa, thus obtaining the polysaccharide antibiotic compound;
the chitosan is carboxymethyl chitosan with the deacetylation degree of more than 80%; the cellulose is hydroxypropyl cellulose or sodium carboxymethyl cellulose; the antibiotic is one of vancomycin, tetracycline, la Sha Junsu and monensin;
the preparation method of the hypochlorous acid comprises the following steps:
s1, pretreating an anode of an electrolytic cell, adding a carbon nano tube into propylene glycol, performing ultrasonic treatment for 30 minutes, coating an electrode reaction catalyst on the anode, and roasting at 200-300 ℃ for 30 minutes to finish the treatment;
s2, introducing 0.1-0.2wt% of sodium chloride or potassium chloride solution into the cathode chamber and the anode chamber, connecting with a power supply of an electrolytic tank, and electrolyzing to obtain hypochlorous acid;
the electrode reaction catalyst is a mixture of platinum dioxide and tin tetrachloride in a mass ratio of 3:1;
the stabilizer comprises one or more of disodium ethylenediamine tetraacetate, sodium silicate and sodium phosphate;
the neutralizer is PBS solution containing 0.5-1wt% of sodium thiosulfate, 0.5-1wt% of lecithin and 1-2wt% of Tween 60.
2. The hypochlorous acid disinfectant as set forth in claim 1, wherein the disinfectant comprises, in parts by weight: 3-5 parts of hypochlorous acid, 11-14 parts of polysaccharide antibiotic compound, 2-4 parts of pyridinium bromide, 6-8 parts of polyvinylpyrrolidone, 6-8 parts of stabilizer, 1-3 parts of neutralizer, 13-16 parts of surfactant and 68-73 parts of deionized water.
3. The hypochlorous acid disinfectant as set forth in claim 1, wherein the disinfectant comprises, in parts by weight: 4 parts of hypochlorous acid, 12 parts of polysaccharide antibiotic compound, 3 parts of pyridinium bromide, 7 parts of polyvinylpyrrolidone, 7 parts of stabilizer, 2 parts of neutralizer, 15 parts of surfactant and 70 parts of deionized water.
4. A hypochlorous acid sanitizing liquid as set forth in claim 1 wherein said surfactant comprises by weight: 2-8 parts of fatty alcohol polyoxyethylene ether, 3-7 parts of sodium dodecyl diphenyl ether disulfonate, 1-4 parts of sodium hexametaphosphate, 8-12 parts of alkylphenol polyoxyethylene and 5-10 parts of nonylphenol polyoxyethylene.
5. The hypochlorous acid disinfectant as set forth in claim 1, wherein the disinfectant is prepared by the steps of:
dissolving pyridinium bromide, polyvinylpyrrolidone and hypochlorous acid in deionized water, adding into a vacuum emulsification stirrer, vacuumizing and stirring for 30min; slowly adding a stabilizer and a neutralizer, stirring while adding, and adjusting the pH value to 5-6; and adding the polysaccharide antibiotic compound, stirring for 20-30 min at 30-35 ℃, slowly adding the surfactant, and stirring for 10-20 min to obtain the hypochlorous acid disinfectant.
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CN111188052A (en) * 2020-02-27 2020-05-22 上海广锋生物科技有限公司 Preparation method of high-performance hypochlorous acid
CN112042667A (en) * 2020-08-21 2020-12-08 山东知能环保科技有限公司 Stable hypochlorous acid disinfectant and preparation method thereof
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