CN112999331A - Preparation method and application of biological sterilization preparation - Google Patents

Preparation method and application of biological sterilization preparation Download PDF

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CN112999331A
CN112999331A CN201911314817.5A CN201911314817A CN112999331A CN 112999331 A CN112999331 A CN 112999331A CN 201911314817 A CN201911314817 A CN 201911314817A CN 112999331 A CN112999331 A CN 112999331A
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叶贵子
黄青山
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Kunshan Biogreen Technology Co ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/10—Peptides having 12 to 20 amino acids
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/50—1,3-Diazoles; Hydrogenated 1,3-diazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
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    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • Y—GENERAL 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
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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Abstract

The invention discloses a biological sterilization preparation, a preparation method and application thereof, wherein the biological sterilization preparation takes water as a carrier and comprises the following components in percentage by weight: biological antibacterial peptide K110.001% -10%; 0.01-1% of polyhexamethylene biguanide (PHMB). The invention has good sterilization effect. The core bactericidal component of the preparation is novel antibacterial peptide which has strong bactericidal effect on staphylococcus aureus, escherichia coli, candida albicans and viruses. The sterilization rate of 99.9 percent can be achieved after 2-5 minutes of in vitro experiment. Has high safety, no toxicity or residue, and high stability, and can be used as prophylactic. The main active component of the invention is biological preparation, which overcomes the defects that the traditional chemical preparation has irritation to mucosa and bacteria are easy to generate drug resistance. Is easy to be accepted by organism and has no toxic and side effect. Is suitable for long-term use or preventive medication.

Description

Preparation method and application of biological sterilization preparation
Technical Field
The invention relates to a biological sterilization preparation, a preparation method and application thereof.
Background
Currently, the clinical pathogen infection is quite serious, and it has become a big killer threatening the health of human beings in recent 20 years. Moreover, more and more bacteria are resistant to antibiotic treatment, thereby posing a serious threat to public health. In the united states, 1998, more life is lost due to drug-resistant bacterial infections than on the vietnam battlefield. Pathogens that can be killed by antibiotics at once with ease such as: staphylococcus aureus, pneumococcus, pseudomonas aeruginosa, candida albicans, escherichia coli and the like are increasingly fierce due to drug resistance, and people are increasingly stranded. The drug-resistant staphylococcus aureus is the most active molecule, and the infection caused by the drug-resistant staphylococcus aureus not only has poor or completely ineffective curative effect under conventional treatment, but also can change the ecological condition of normal flora of patients, thereby causing additional pain to the patients, and increasing economic burden and unfortunate property.
The common antibacterial agents in the market at present contain chlorine, aldehydes, alcohols, iodine, phenols, quaternary ammonium salts and the like, and have the problems of stimulation to skin mucosa, narrow antibacterial spectrum, bacterial drug resistance for a long time and the like. Particularly, the antibacterial agent applied to sensitive parts has higher requirements on the formula of the preparation, such as the special antibacterial agent for female private parts. Bacterial, mycotic, trichomonas and nonspecific vaginitis, cervicitis, vulvitis, pudendal pruritus and the like are commonly generated at private parts of women. Due to the sensitivity of the parts, the requirements on treatment medicines are higher, common existing disinfectants can stimulate skin mucosa, the antibacterial spectrum is not wide enough, or bacterial resistance is easily caused due to the antibacterial mechanism, so that the existing disinfectants are not suitable for long-term use and prevention use, and have a plurality of defects and cannot meet the requirements.
Disclosure of Invention
The invention aims to disclose a biological sterilization preparation, a preparation method and application thereof, which aim to overcome the defects in the prior art.
The biological sterilization preparation takes water as a carrier and comprises the following components in percentage by weight:
biological antibacterial peptide K110.001% -10%;
polyhexamethylene biguanide (PHMB) 0.01-1%
Preferably, the carrier is water, and the carrier comprises the following components in percentage by weight:
biological antibacterial peptide K110.001% -2%;
polyhexamethylene biguanide (PHMB) 0.01-0.5%
The biological antibacterial peptide K11 is a polypeptide with an amino acid sequence of Lys Trp Lys Ser Phe Ile Lys Lys Leu Thr Lys Lys Phe Leu His Ser Ala Lys Lys Phe, and the preparation, purification and properties of the biological antibacterial peptide K11 are described in patent of invention No. CN 101570569B;
the biological antibacterial peptide K11 is a biological protein, and in a liquid preparation, the protein activity is important to maintain, but general chemical reagents, especially high molecular materials and surfactant components can influence the protein activity;
the inventor finds that polyhexamethylene biguanide is a compound which has no influence on the activity of the antimicrobial peptide K11, and the two can be used together. Polyhexamethylene biguanide is a good broad-spectrum bactericide, and can be combined with antibacterial peptide K11 to exert the antibacterial effect of the preparation greatly. The protein activity of the antibacterial peptide K11 can be well maintained under the condition that the concentration of the polyhexamethylene biguanide is extremely low (one ten thousandth of the weight content), so that the effect of the antibacterial peptide K11 is exerted to the maximum;
preferably, the biological bactericidal preparation takes water as a carrier, and also comprises pharmaceutically acceptable auxiliary materials, phosphate, such as disodium hydrogen phosphate and potassium dihydrogen phosphate; protective agents, such as glycine; stabilizers, such as chitosan; emollients, such as glycerin; inorganic salts such as sodium chloride, potassium chloride;
further preferably, the biological sterilization preparation takes water as a carrier and comprises the following components in percentage by weight:
Figure BSA0000197736660000021
most preferably, the carrier is water, and the carrier comprises the following components in percentage by weight:
Figure BSA0000197736660000022
Figure BSA0000197736660000031
the preparation method comprises the following steps:
(1) dissolving the disodium hydrogen phosphate and the monopotassium phosphate in water to obtain a solution A;
(2) dissolving biological antibacterial peptide K11, polyhexamethylene biguanide and glycine in the solution A, and then dissolving chitosan and sodium chloride in water to obtain a solution B;
(3) mixing the solution A and the solution B, and adding glycerol to obtain the biological bactericidal preparation;
animal experiments prove that the biological sterilization preparation has very good sterilization effect, particularly has obvious killing effect on staphylococcus aureus, candida albicans, escherichia coli and viruses, can be widely, safely and practically used for sterilizing hands, skins and mucous membranes, and sterilizing the surfaces of common articles including food and drink utensils in places such as families, restaurants, hotels, public transport means, kindergartens, hospitals and the like, and air sterilization, animal sterilization, pet sterilization and the like.
The biological sterilization preparation can be applied to the part needing sterilization through the ways of dipping, smearing and spraying, the dosage is generally 1-3 times a day, and the dosage is used every time to uniformly cover the sterilized surface part.
The biological bactericidal preparation provided by the invention is characterized in that the antibacterial peptide K11 and the polyhexamethylene biguanide compound are not simply added in function, but have a synergistic enhancement effect, and the bactericidal effect of the compound is 2-20 times that of the simple addition of the two bactericidal effects. The bactericidal spectrum of the compound is also obviously expanded, and the compound can achieve good killing effect on gram-positive bacteria, gram-negative bacteria and common viruses, especially on drug-resistant gram-positive bacteria and gram-negative bacteria which are difficult to treat by common bactericides.
The biological bactericidal preparation has the beneficial effects that:
1. the sterilizing effect is good. The core bactericidal component of the preparation is novel antibacterial peptide which has strong bactericidal effect on staphylococcus aureus, escherichia coli and candida albicans. The sterilization rate of 99.9 percent can be achieved after 2 minutes of in vitro experiment, and the sterilization rate can reach 100 percent if 5 to 10 minutes of in vitro experiment is performed.
2. The safety is high: the core bactericidal component of the preparation is biological protein, and can be degraded into amino acid quickly even after being absorbed by tissues, so that the problem of toxicity or residue on human bodies can be avoided.
3. The stability is strong. The product is stored at 25 deg.C for six months, and the bioactivity is not changed basically. The product can be preserved for 2 years at 4-8 deg.C.
4. Can be used as preventive medicine: the main active component of the invention is biological preparation, which overcomes the defects that the traditional chemical preparation has irritation to mucosa and bacteria are easy to generate drug resistance. Is easy to be accepted by organism and has no toxic and side effect. Is suitable for long-term use or preventive medication.
Detailed Description
Example 1
1. The components and the proportion are as follows: (weight percent)
Biological antibacterial peptide K110.001%; 1% of polyhexamethylene biguanide (PHMB); 1% of glycine; 1% of chitosan; 1% of glycerol; 1% of monopotassium phosphate; 1% of disodium hydrogen phosphate; 0.1% of sodium chloride; the rest is distilled water.
2. Preparation step
(1) Dissolving potassium dihydrogen phosphate and disodium hydrogen phosphate in distilled water to obtain solution A;
(2) according to the preparation formula, the required biological antibacterial peptide K11, polyhexamethylene biguanide and glycine are weighed and added into the solution A, and the solution B is obtained by stirring and dissolving.
(3) Weighing chitosan and sodium chloride according to a ratio, and dissolving in distilled water to obtain a solution C;
(4) and mixing the solution B and the solution C, adding glycerol, and uniformly stirring to obtain a finished product.
Subpackaging into plastic or glass bottles for direct use as a disinfectant; or packaging into spray bottle with manual pump to obtain disinfectant spray; can also be used as wet towel additive solution to be adsorbed in nonwoven fabric to make into sanitary wet towel.
Example 2
1. The components and the proportion are as follows: (weight percent)
Biological antibacterial peptide K1110%; polyhexamethylene biguanide (PHMB) 0.01%; 8% of glycine; 10% of chitosan; 5% of glycerol; 20% of monopotassium phosphate; 30% of disodium hydrogen phosphate; 2% of sodium chloride; the balance is distilled water, and the total weight percentage of all the components is 100 percent.
2. The preparation method is the same as that of example 1;
subpackaging into plastic or glass bottles for direct use as a disinfectant; or packaging into spray bottle with manual pump to obtain disinfectant spray; can also be used as wet towel additive solution to be adsorbed in nonwoven fabric to make into sanitary wet towel.
Example 3
1. Composition and proportion
Biological antibacterial peptide K111%; polyhexamethylene biguanide (PHMB) 0.02%; 2% of glycine; 2% of chitosan; 3% of glycerol; 10% of monopotassium phosphate; 20% of disodium hydrogen phosphate; 1% of sodium chloride; the balance is distilled water, and the total weight percentage of all the components is 100 percent.
2. The preparation method is the same as example 1.
Subpackaging into plastic or glass bottles for direct use as a disinfectant; or packaging into spray bottle with manual pump to obtain disinfectant spray; can also be used as wet towel additive solution to be adsorbed in nonwoven fabric to make into sanitary wet towel.
Example 4
1. Composition and proportion
110.1% of biological antibacterial peptide K; polyhexamethylene biguanide (PHMB) 0.01%; 8% of glycine; 10% of chitosan; 80% of glycerol; 5% of monopotassium phosphate; 10% of disodium hydrogen phosphate; 0.75% of sodium chloride; the balance is distilled water, and the total weight percentage of all the components is 100 percent.
2. The preparation method is the same as example 1.
Subpackaging in plastic or glass bottle as smearing agent.
Example 5
The following table shows the comparison of the killing effect of the antimicrobial peptide K11 and the antimicrobial peptide K11 compound on various microorganisms (the microorganism sterilization rate test is carried out according to the relevant regulations of GB15979-2002 _1_2002-03-05_ 0):
Figure BSA0000197736660000051
the above table shows that the bactericidal effect of the antimicrobial peptide K11 and the polyhexamethylene biguanide compound is not the simple superposition of the bactericidal effects of the two substances, and the antimicrobial peptide K11 and the polyhexamethylene biguanide are used together, so that the antimicrobial effect of the antimicrobial peptide K11 can be greatly exerted. And the protein activity of the antibacterial peptide K11 can be well maintained under the condition that the concentration of the polyhexamethylene biguanide is extremely low (one ten thousandth of the weight content), the effective action concentration of the antibacterial peptide K11 is reduced, and the same high-efficiency bactericidal effect can be still achieved.
Example 6
The clinical trial report of the biological bactericidal preparation of the invention shows that the biological bactericidal preparation has the following effects:
test one: sterilization experiment of biological bactericidal preparation on staphylococcus aureus and escherichia coli
First, equipment
1. Test bacteria: staphylococcus aureus generation 6 (provided by the center for testing the Disinfection of the military medical academy of sciences), Escherichia coli generation 6 (provided by the center for testing the Disinfection of the military medical academy of sciences)
2. Sample preparation: the biological fungicidal preparation of example 1
3. Neutralizing agent: D/E broth of 2% histidine, 8% lecithin wax, 10% tween-80
4. PBS: 0.03mol/L phosphate buffer solution
5. GNP-9160 type water-proof constant temperature incubator (Shanghai Jing hong experiment equipment Co., Ltd.)
6. Culture medium: common nutrient agar
7. Mechanical stopwatch (504 type)
8. Adjustable constant temperature water bath box (CBN28-3)
Second, method
1. The inspection basis is as follows: sanitary Standard for Disposable sanitary articles GB15979-2002 appendix C3
2. And (3) identification test of a neutralizer: test strains: concentration of staphylococcus aureus sample: 1: 20 diluent, action time: 0.5min
3. Quantitative sterilization test: sample concentration: 1: 20 dilution
4. The test temperature is 20 ℃, and the test is repeated for 3 times
Three, result in
1. Test temperature 20 ℃, sample 1: the sterilization rate of the diluent to staphylococcus aureus and escherichia coli is 100% in 2 minutes, 5 minutes, 10 minutes and 20 minutes.
TABLE 2 Sterilization effect on the test bacteria
Figure BSA0000197736660000071
Example 7
And (2) test II: experiment of the Biocide preparation of example 1 against Candida albicans
First, equipment
1. Test bacteria: candida albicans generation 6 (provided by military medical science institute disinfection detection center)
2. Sample preparation: biological bactericidal preparation
3. Neutralizing agent: D/E broth of 2% histidine, 8% lecithin wax, 10% tween-80
4. PBS: 0.03mol/L phosphate buffer solution
5. GNP-9160 type water-proof constant temperature incubator (Shanghai Jing hong experiment equipment Co., Ltd.)
6. Culture medium: sabouraud's medium
7. Mechanical stopwatch (504 type)
8. Adjustable constant temperature water bath box (CBN28-3)
Second, method
1. The inspection basis is as follows: sanitary Standard for Disposable sanitary articles GB15979-2002 appendix C3
2. And (3) identification test of a neutralizer: sample concentration: stock solution, action time: 0.5min
3. Quantitative sterilization test: sample concentration: stock solution
4. The test temperature is 20 ℃, and the test is repeated for 3 times
Three, result in
1. Test temperature 20 ℃, sample 1: the sterilization rate of the candida albicans in the dilution liquid is 100% in 2 minutes, 5 minutes, 10 minutes and 20 minutes.
TABLE 4 Sterilization effect on the test bacteria
Figure BSA0000197736660000081
Example 8
And (3) test III: experiment of influenza Virus killing by the Biogermicidal formulation of example 3
1. Materials and methods
1.1 test sample: the biocidal formulation of example 3.
1.2 test strains:
influenza virus (H)3N2)
1.3 test basis:
the Ministry of health, Disinfection technical Specification.
2. Inactivation test results for influenza virus
Under the condition that the test temperature is 20 +/-1 ℃, the test is repeated for 3 times, the test sample stock solution acts for 5.0min, and the average killing logarithm value of the influenza virus is more than 5.00. (results are shown in Table 5)
TABLE 5 inactivation Effect on influenza viruses
Figure BSA0000197736660000082
Note: the positive control mean log value and range 4.32 (4.23-4.50).
Example 9
And (3) test III: vaginal mucosa irritation test of the Biocide formulation of example 2
Materials and animals
1. The test substance: the sample is colorless liquid, the original liquid of the sample is taken as a tested substance,
2. animals: 6 healthy female New Zealand white rabbits, the common grade, provided in the Jinling breeding rabbit farm, the certification number: SCXK (Su) No. 2012-0003, weight 2.0-2.4 kg.
3. The test conditions are as follows: animal environmental facility certification number: SYXK (Su) Nos. 2012-0036; ambient temperature: 22 +/-2 ℃; relative humidity: 40-70 percent; feed source and identification number: jiangsu province, cooperative pharmaceutical bioengineering, Inc., Su A gao Sheng (2002) 009. The main apparatus is as follows: infant scales (05-324), pathological microtomes, microscopes.
Second, method
1. The inspection basis is as follows: the second part of the "Disinfection Specification" of the Ministry of health (2002) 2.3.5 vaginal mucosa irritation test.
2. The test method comprises the following steps: animals were divided into test and control groups of 3 animals each. The animal is fixed on the back, and the perineum and the vaginal orifice are exposed. A small size catheter was connected to a 2mL syringe, moistened with the test substance, gently inserted into the animal's vagina (4-5cm), slowly injected into 2mL of the test substance, and the catheter was withdrawn to complete the staining. The animals in the control group are treated by normal saline in the same way, the animals are killed by an air embolism method after 24mL, the complete vagina is taken out after the abdominal incision, the longitudinal incision is carried out, the appearance of congestion, edema and the like is observed by naked eyes, the vagina is fixed in 10% formalin for more than 24 hours for reference when pathological material is obtained, tissues at two ends and 3 parts in the center of the vagina are selected for flaking, and histopathological examination is carried out after HE staining.
Third, experimental results
The mild moderate edema of the vaginal mucosa of each animal in the control group No. 2 and the test group can be seen by visual observation. Histopathological observations are shown in the table below.
Test substance response to vaginal mucosal irritation in animals
Figure BSA0000197736660000091
Fourth, conclusion
The stimulation index of the tested substance to the rabbit vaginal mucosa is 1.0, and the stimulation intensity of the vaginal mucosa is extremely light stimulation.

Claims (10)

1. The biological sterilization preparation is characterized by taking water as a carrier and comprising the following components in percentage by weight:
biological antibacterial peptide K110.001% -10%;
0.01-1% of polyhexamethylene biguanide (PHMB).
2. The biological sterilization preparation as claimed in claim 1, which is characterized in that water is used as a carrier, and the biological sterilization preparation comprises the following components in percentage by weight:
biological antibacterial peptide K110.001% -2%;
0.01-0.5% of polyhexamethylene biguanide (PHMB).
3. The biological bactericidal preparation according to claim 1 or 2, characterized in that water is used as a carrier and pharmaceutically acceptable auxiliary materials are further included.
4. The biological bactericidal preparation according to claim 3, wherein the biological bactericidal preparation takes water as a carrier and comprises the following components in percentage by weight:
Figure FSA0000197736650000011
5. the biological bactericidal preparation according to claim 3, wherein the biological bactericidal preparation takes water as a carrier and comprises the following components in percentage by weight:
Figure FSA0000197736650000012
Figure FSA0000197736650000021
6. the method for preparing a biological bactericidal agent according to any one of claims 1 to 5, characterized by comprising the steps of:
(1) dissolving the disodium hydrogen phosphate and the monopotassium phosphate in water to obtain a solution A;
(2) dissolving biological antibacterial peptide K17, polyhexamethylene biguanide and glycine in the solution A, and then dissolving chitosan and sodium chloride in water to obtain a solution B;
(3) and mixing the solution A and the solution B, and adding glycerol to obtain the biological bactericidal preparation.
7. The use of the biological bactericidal agent according to any one of claims 1 to 5 for disinfection of hands, skin, mucous membranes, and surfaces of general articles including eating and drinking utensils in home, restaurants, hotels, public transportation vehicles, kindergartens, and hospital settings, and for disinfection of air, animals, and pets.
8. Use according to claim 7, characterized in that it is applied to the area to be disinfected by means of dipping, painting or spraying.
9. Use according to claim 8, wherein the dose is 1 to 3 times a day, each time in an amount to provide uniform coverage of the sterilized surface area.
10. Use of a biocidal formulation according to claim 1 or 2 in the preparation of a disinfectant.
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CN115152793A (en) * 2022-07-25 2022-10-11 独春堂生物科技研究院(菏泽)有限公司 Purifying agent for ICU ward purification and preparation method thereof
CN115399339A (en) * 2022-09-19 2022-11-29 深圳市减化生物科技有限公司 Biological bactericide, preparation method thereof and biological bactericide product

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113841637A (en) * 2021-08-24 2021-12-28 中国水产科学研究院珠江水产研究所 Hybrid snakehead rhabdovirus-free fry breeding method
CN115152793A (en) * 2022-07-25 2022-10-11 独春堂生物科技研究院(菏泽)有限公司 Purifying agent for ICU ward purification and preparation method thereof
CN115399339A (en) * 2022-09-19 2022-11-29 深圳市减化生物科技有限公司 Biological bactericide, preparation method thereof and biological bactericide product

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