CN114916544A - Compound foam type long-acting disinfectant containing citric acid and preparation method and application thereof - Google Patents

Compound foam type long-acting disinfectant containing citric acid and preparation method and application thereof Download PDF

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CN114916544A
CN114916544A CN202210502856.3A CN202210502856A CN114916544A CN 114916544 A CN114916544 A CN 114916544A CN 202210502856 A CN202210502856 A CN 202210502856A CN 114916544 A CN114916544 A CN 114916544A
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citric acid
bromide
disinfectant
stirring
glutaraldehyde
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李秀波
徐飞
张蒙蒙
刘欢
王欢欢
陈孝杰
刘义明
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Feed Research Institute of Chinese Academy of Agricultural Sciences
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Feed Research Institute of Chinese Academy of Agricultural Sciences
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    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01PBIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P1/00Disinfectants; Antimicrobial compounds or mixtures thereof
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION 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
    • A01N33/00Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds
    • A01N33/02Amines; Quaternary ammonium compounds
    • A01N33/12Quaternary ammonium compounds
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION 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
    • A01N25/00Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/16Foams
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION 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
    • A01N35/00Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical
    • A01N35/02Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical containing aliphatically bound aldehyde or keto groups, or thio analogues thereof; Derivatives thereof, e.g. acetals
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION 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
    • A01N37/00Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/36Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a singly bound oxygen or sulfur atom attached to the same carbon skeleton, this oxygen or sulfur atom not being a member of a carboxylic group or of a thio analogue, or of a derivative thereof, e.g. hydroxy-carboxylic acids
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION 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
    • A01N47/00Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/40Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides
    • A01N47/42Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides containing —N=CX2 groups, e.g. isothiourea
    • A01N47/44Guanidine; Derivatives thereof
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01PBIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P3/00Fungicides
    • 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

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  • Wood Science & Technology (AREA)
  • Environmental Sciences (AREA)
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  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Dentistry (AREA)
  • Pest Control & Pesticides (AREA)
  • Agronomy & Crop Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Toxicology (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

The invention discloses a compound foam type long-acting disinfectant containing citric acid, and a preparation method and application thereof. The disinfectant comprises the following components in percentage by mass: 0.5-5.0% of citric acid, 0.5-5.0% of benzalkonium bromide, 0.5-5.0% of decamethyl bromide, 0.25-2.5% of glutaraldehyde, 0.5-5.0% of polyhexamethylene biguanide, 3.0-15.0% of cosolvent, 0.1-0.5% of penetrating agent, 0.5-5.0% of foam emulsifier, stabilizer and citric acid can form a buffer system, the pH value is kept to be 3.0-5.0, and the sterilized water is supplemented to 100%. The compounded disinfectant has synergistic or additive effect, kills all pathogenic microorganisms of animal sources including bacteria, viruses, mycoplasma, fungi and the like existing in the covering culture environment, and has the sterilization efficiency of 100 percent.

Description

Compound foam type long-acting disinfectant containing citric acid and preparation method and application thereof
Technical Field
The invention belongs to the field of biological safety protection articles in livestock and poultry breeding, and particularly relates to a compound foam type long-acting disinfectant containing citric acid, and a preparation method and application thereof.
Background
The serious epidemic diseases of the livestock and poultry seriously damage the development of the breeding industry and threaten the health and public health safety of human beings all the time. Strengthen the prevention and control of animal major epidemic diseases and foreign animal epidemic diseases, and is a great demand for guaranteeing the supply safety of livestock and poultry products and the national biological safety.
The biological safety prevention and control product plays an extremely important role in epidemic disease prevention and control, and the disinfectant is an important component of the biological safety prevention and control product. However, the existing biosafety prevention and control products have some outstanding problems, and the existing products have the problems of low sterilization efficiency, poor safety, poor durability and the like, and lack of breakthrough innovation technology.
The first problem is that: low sterilization efficiency
At present, animal-derived pathogenic microorganisms in a breeding environment comprise bacteria, viruses, mycoplasma, fungi and the like, and often one disinfectant product cannot effectively kill all pathogenic microorganisms, and the commonly used quaternary ammonium salt disinfectant has poor killing effect on spores, mycoplasma and the like of bacteria. Therefore, the problem of low sterilization efficiency is solved by carrying out compound proportioning according to different sterilization spectrums of the disinfectant;
the second problem is that: poor safety
The disinfection of plant is a continuous process, and the product consumption is big, in order to pursue the reduction of cost, often adopt great toxicity disinfection products such as caustic soda (active ingredient is sodium hydroxide), aldehydes (formaldehyde, glutaraldehyde), phenols (phenol), on the one hand has caused the injury to the place animal, also has potential toxic effect to the workman that plant's disinfection used. Many cases of animal death have been reported due to overuse or improper use of disinfectants. The development of a disinfectant which is green, environment-friendly and high in safety is very necessary;
the third problem is that: poor durability
At present, the disinfectant is generally a solution in the using process, and is sprayed on objects such as handrails, cribs or the ground of a livestock house, and due to the high fluidity of the solution, the adhesion and the durability of the disinfectant are poor on irregular surfaces such as handrails and uneven ground, the disinfectant is difficult to fully contact with the objects, the sterilization efficiency is low, and the excessive consumption of the disinfectant is caused by the need of improving the sterilization frequency. This problem makes it possible to develop a disinfecting product with a long-lasting foam, increasing the adhesion and adherence, and giving a long-lasting kill.
Therefore, the development of a green, efficient, safe and low-cost biosafety prevention and control product is urgently needed, the industrial popularization and application are realized, and the green and continuous healthy development of the animal husbandry in China is promoted.
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides a compound foam type long-acting disinfectant containing citric acid and a preparation method thereof, wherein the disinfectant is environment-friendly, efficient, low in price, free of residues, good in sterilization effect and convenient to transport.
The compound foam type long-acting disinfectant containing citric acid provided by the invention comprises the following components in percentage by mass
Figure BDA0003636096500000021
Further, the compound foam type long-acting disinfectant containing citric acid comprises the following components in percentage by mass
Figure BDA0003636096500000022
Preferably, the ratio of the mass of glutaraldehyde to the sum of the masses of benzalkonium bromide and decamethyl bromide may be 1: 2 or more, more preferably 1: (2-4), specifically 1: 2 or 1: 3 or 1: 4;
preferably, the mass ratio of the benzalkonium bromide to the decamethyl bromide can be 1: (1-4), more preferably 1: (1-3), specifically 1: 1 or 1: 2 or 1: 3 or 1: 4;
preferably, the cosolvent can be selected from one or more of alcohol solvents containing 2-10 carbon atoms, such as one or more of alcohol solvents of ethanol, propylene glycol, butanol, isobutanol, octanol and the like;
preferably, the penetrating agent can be selected from one or more of ethanol, glycerol trioleate, tricaprylin, fatty acid polyoxyethylene ether-9, fatty acid polyoxyethylene ether-7, fatty acid polyoxyethylene ether-5 and the like;
preferably, the foam emulsifier can be selected from one or more of dodecyl dimethyl amine oxide, decyl glucoside, coconut oil diethanol amide and hexadecyl trimethyl ammonium bromide; specifically, the foam emulsifier is decyl glucoside, and the mass content of the decyl glucoside is preferably 1%; the foam emulsifier is coconut oil diethanolamide or hexadecyl trimethyl ammonium bromide, and the mass content of the foam emulsifier is preferably 3%.
Preferably, the stabilizer is selected from salts that can form a buffer system with citric acid, such as citrate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, sodium hydrogen phosphate, and the like.
The invention also provides a preparation method of the compound foam type long-acting disinfectant containing citric acid.
The preparation method of the compound foam type long-acting disinfectant containing citric acid provided by the invention comprises the following steps:
(1) introducing nitrogen into part of the sterilized water;
(2) adding the cosolvent into the sterilized water treated in the step (1) and stirring;
(3) adding the decamethyl ammonium bromide and benzalkonium bromide to the system obtained in the step (2) and stirring at a low speed (<150rpm) until complete dissolution;
(4) adding the penetrant and the foam emulsifier into the system obtained in the step (3) and stirring at a low speed (<150rpm) to form a system A;
(5) introducing nitrogen into another part of the sterilized water;
(6) adding the glutaraldehyde and the polyhexamethylene biguanide into the sterilized water treated in the step (5) and stirring at a low speed (<150rpm) until the glutaraldehyde and the polyhexamethylene biguanide are completely dissolved;
(7) adding the citric acid and the stabilizing agent into the system obtained in the step (6), and stirring at a low speed (<150rpm) until the citric acid and the stabilizing agent are completely dissolved; forming a system B;
(8) and transferring the system B into the system A, uniformly stirring at a low speed (<150rpm), metering to 100% by mass with the sterilized water, and keeping the pH value of the system between 3.0 and 5.0.
In the method, the rotation speed of the low-speed stirring is less than 150 rpm.
In the step (4), the stirring time may be 20-60 min.
The compound foam type long-acting disinfectant containing citric acid provided by the invention can effectively kill common pathogenic microorganisms such as bacteria, viruses, mycoplasma, spores, fungi and the like on the ground, railings, food troughs and the like in an animal husbandry environment.
The virus can be hog cholera virus (such as Thiveral hog cholera virus), newcastle disease virus (such as LaSota newcastle disease virus), etc.
The spore is specifically Bacillus subtilis.
The invention also provides a disinfectant composition.
The disinfectant composition protected by the invention comprises citric acid, benzalkonium bromide, decamethyl ammonium bromide, glutaraldehyde and polyhexamethylene biguanide.
Wherein the ratio of the mass of the glutaraldehyde to the sum of the masses of the benzalkonium bromide and the decamethylammonium bromide is 1: 2 and above, preferably 1: (2-4);
the mass ratio of the benzalkonium bromide to the decamethyl bromide is 1: (1-4), preferably 1: (1-3);
the mass ratio of the polyhexamethylene biguanide to the glutaraldehyde is 1: (0.5-5), preferably 1: (1-3);
the mass ratio of the citric acid to the glutaraldehyde is 1: (1-10), preferably 1: (1-8).
Aiming at the problem of low sterilization efficiency of the existing disinfectant. The invention provides a compound formula, which has synergistic effect and can effectively solve the problem of low single-formula sterilization efficiency. The action analysis of each component in the formula is as follows:
1. benzalkonium bromide and decamethyl ammonium bromide are two cationic surfactants, and are enriched on the surface of a cell wall, so that the filtering effect of a microbial cell membrane is disturbed, the permeability of bacterial cells is increased, water permeates into bacteria to cause substance leakage, the metabolism of the bacteria is influenced to destroy the cell structure, and finally the bacteria are dead. The disinfectant has low toxicity and the like, and the disinfectant has high toxicity,
the detergent has strong decontamination capability, is non-corrosive to metal materials, has a synergistic bactericidal effect, has good killing capability to common animal-derived bacteria, but has poor effect on bacterial spores.
2. The killing effect of glutaraldehyde on microbe depends mainly on aldehyde group, and mainly acts on mercapto, hydroxyl, carboxyl and amino of mycoprotein, so that it can make it alkylate to cause protein coagulation to result in bacterial death, and has good killing effect on virus, bacterial spore, fungus and spore and other microbes.
3. Polyhexamethylene biguanide belongs to an environment-friendly disinfectant, guanidino has high activity, and the polymer can be electropositive and can be easily adsorbed by various electronegative bacteria, so that the splitting function of the bacteria and the like is inhibited, and the reproductive capacity of the bacteria and the like is lost.
4. Citric acid, also known as citric acid, having the molecular formula C 6 H 8 O 7 The compound is an important organic acid, is a colorless crystal, is odorless, has strong sour taste, is easy to dissolve in water, can be used as a pH regulator, and has a good killing effect on animal-derived mycoplasma under the condition of low concentration (0.5-1.0%) in the previous experimental study of an inventor.
Test results show that the components of the formula can cooperate with each other to kill all pathogenic microorganisms of animal origin including bacteria, viruses, mycoplasma, fungi and the like existing in the covering culture environment, and the sterilization efficiency is 100%.
Aiming at the problem of poor sterilization safety of the existing disinfectant. In the invention, only glutaraldehyde belongs to aldehyde products and has certain irritation and corrosivity, but due to mutual synergy, the use concentration of glutaraldehyde in the compound is reduced by more than 60-80% compared with that in a single formula, and the toxicity test result shows that the formula product is safe, effective and non-irritating to use.
Aiming at the problem of poor sterilization durability of the existing disinfectant. In the formula of the invention, the SF penetrant containing penetrant, cosolvent, stabilizer and foam forming agent, especially polyhexamethylene biguanide is a high molecular polymer, the product forms a high molecular solution state, and is easy to adsorb various negatively charged bacteria and the like, and rich foam is formed by a foaming gun or a foaming machine when the disinfectant is used, and the foam is attached to the surface of the disinfectant body to play a long-acting and lasting disinfection role.
Compared with the prior art, the invention has the following beneficial effects:
(1) the sterilization range is wide. Because the compounded disinfectant has synergistic or additive effect, the total bactericidal capacity after compounding is enhanced. Quaternary ammonium salts generally cannot kill bacterial spores, and aldehyde disinfectants have good effect on killing bacterial spores. The invention can kill all pathogenic microorganisms of animal origin, including bacteria, viruses, mycoplasma, fungi and the like, existing in the covering and breeding environment by the synergistic action of quaternary ammonium salts, aldehydes, acids and guanidine compounds, and the sterilization efficiency is 100%.
(2) Long-acting and durable. In the formula of the invention, the SF penetrant containing penetrant, cosolvent, stabilizer and foam forming agent, especially polyhexamethylene biguanide is a high molecular polymer, the product forms a high molecular solution state, and is easy to adsorb with various negatively charged bacteria and the like, rich foam is formed by a foaming gun or a foaming machine when the disinfectant is used, and the foam is attached to the surface of a disinfectant body to play a long-acting and lasting disinfection role.
(3) The safety is high. The aldehyde disinfectant has skin irritation and acute toxicity, and in the invention, the dosage of glutaraldehyde is greatly reduced by only 20% of the original dosage through the effective formula synergy, so that the disinfectant has no toxic or side effect on human bodies, and animal toxicological tests show that the formula is efficient, safe and nontoxic.
(4) Can effectively kill mycoplasma. Mycoplasma, as a pathogen, has vertical, horizontal and mechanical transmission capability, and complex and diverse infection routes, and can widely survive in a breeding environment depending on organic biomass. Compared with the prior art, the invention can effectively kill mycoplasma in the culture environment and has important function for effectively controlling the propagation of mycoplasma diseases in the culture farm.
(5) The production process is simple, the stability is good, the expanded production is easy, the on-site disinfection effect is obvious, and the popularization value is very high.
Detailed Description
The present invention will be further illustrated with reference to the following examples, but the present invention is not limited to the following examples. The method is a conventional method unless otherwise specified. The starting materials are commercially available from the open literature unless otherwise specified.
Examples 1,
(1) Synergistic screening of glutaraldehyde and quaternary ammonium salt content
Recovering the glutaraldehyde, the decamethyl ammonium bromide and the benzalkonium bromide to room temperature, wherein the ratio (mass ratio) of the decamethyl ammonium bromide to the benzalkonium bromide is 1: 1, PBS solution is used as a solvent, different disinfectant groups are respectively prepared according to the table 1, bacillus subtilis CMCC (B)63501 is used as an indicator bacterium, a suspension quantitative sterilization test is carried out, and the sterilization rate is used as a screening basis.
TABLE 1 test results for the ratio of glutaraldehyde to quaternary ammonium salt
Figure BDA0003636096500000051
Figure BDA0003636096500000061
Note: the above results are the average of 3 trials; the test conditions are all 20 +/-2 ℃; 1, disinfectant: 2 times of dilution, and the action time is 1 h.
The results show that: in group 8, the quaternary ammonium salt is used alone, the spore killing capability is very low (7.8%), the 1% glutaraldehyde compound mass concentration is 0.1% -4% of the quaternary ammonium salt solution, and the sterilization rate is increased along with the increase of the quaternary ammonium salt content. The test result shows that the ratio of the glutaraldehyde to the quaternary ammonium salt is equal to or more than 1: 2 and above, the sterilization rate can reach more than 99.90 percent, and the disinfection effect is qualified.
(2) Synergistic screening of two quaternary ammonium salt contents
The glutaraldehyde, the decamethylammonium bromide and the benzalkonium bromide bulk drugs are returned to room temperature, disinfectant mixed liquor groups for experiments are respectively prepared according to the table 2, and a suspension quantitative sterilization test is carried out by taking bacillus subtilis 63501 as an indicator bacterium. The results were as follows:
TABLE 2 benzalkonium bromide to decamethylammonium bromide ratio test results
Figure BDA0003636096500000062
Note: the above results are the average of 3 trials; the test conditions are all 20 +/-1 ℃; 1, disinfectant: diluting for 2 times, and acting for 1 h.
The results show that: under the condition that the total content of 1% of glutaraldehyde and 2% of quaternary ammonium salt is constant, the sterilization rate is increased along with the increase of the proportion of decamethyl ammonium bromide. The bactericidal ratio of decamethylammonium bromide to benzalkonium bromide is equal to 1: 1, the bactericidal rate is 99.92%, when being equal to 2: 1, the sterilization rate is 99.98%, and is equal to 3: 1 hour, the sterilization rate is equal to 100 percent, and the disinfection effect is qualified.
(3) Polyhexamethylene biguanide content synergistic screening
The content of polyhexamethylene biguanide is screened, disinfectant mixed liquid groups for experiments are prepared according to the table 3, and a suspension quantitative sterilization test is carried out by taking bacillus subtilis 63501 as an indicator bacterium. The results were as follows:
TABLE 3 polyhexamethylene biguanide formulation test results (%)
Figure BDA0003636096500000063
Figure BDA0003636096500000071
The results show that: the content of the polyhexamethylene biguanide is between 0.5 and 1.5 percent, the sterilization rate of each group is more than 99.9 percent, and the disinfection effect is qualified.
(4) Synergistic screening of citric acid content
Screening the citric acid content, respectively preparing disinfectant mixed liquor for experiments according to table 4, and performing suspension quantitative sterilization test by using 10 clinical bovine mycoplasma pathogens (BS1738-BS1748) as indicator bacteria. The results are as follows:
table 4 screening results of citric acid content in System (%)
Figure BDA0003636096500000072
The results show that: the citric acid content is between 0.5 percent and 4.0 percent, the sterilization rate of each group is more than 99.9 percent, and the disinfection effect is qualified.
(5) Foam emulsifier screening
Screening coconut oil diethanolamide, decyl glucoside and cetyl trimethyl ammonium bromide emulsifier with the content of 1-3% respectively. And (5) testing results. The foam of 1% decyl glucoside is rich and fine, and the foam duration is as long as 60 min. Whereas the 1% coconut oil diethanolamide, 1% cetyltrimethylammonium bromide foam was rare for short duration and at 60min the 1% coconut oil diethanolamide foam completely subsided. 3 percent of coconut oil diethanolamide and 3 percent of hexadecyl trimethyl ammonium bromide can meet the requirement that the foam duration is as long as 60 min.
Example 2 Compound foam type Long-acting disinfectant containing citric acid
The formulation is shown in the following table.
Figure BDA0003636096500000073
Figure BDA0003636096500000081
According to the components and the content (w/w), 1.0kg of compound foam type long-acting disinfectant is prepared, and the specific steps are as follows:
(1) introducing nitrogen into part of the sterilized water;
(2) adding propylene glycol to the sterilized water and stirring;
(3) adding the decamethyl bromide and benzalkonium bromide into the system obtained in the step (2) and stirring at a low speed (<150rpm) until complete dissolution;
(4) adding fatty acid polyoxyethylene ether-9 and decyl glucoside into the system obtained in the step (3), and stirring at a low speed (<150rpm) for 20min to form a body system A;
(5) introducing nitrogen into another part of the sterilized water;
(6) adding glutaraldehyde and polyhexamethylene biguanide to the sterilized water and stirring at low speed (<150rpm) to dissolve completely;
(7) adding the citric acid and sodium citrate into the system obtained in the step (6), and stirring at a low speed (<150rpm) until the citric acid and the sodium citrate are completely dissolved; forming a system B;
(8) and transferring the system B into the system A, stirring at a low speed (<150rpm) for 20min, metering the balance by using the sterilized water according to the mass, and measuring the pH of the system to be between 3.0 and 5.0.
Example 3 Compound foam type Long-acting disinfectant containing citric acid
The formulation is shown in the following table.
Citric acid 0.5%
Benzalkonium bromide 1.5%
Decamethylammonium bromide 3.0%
Glutaraldehyde 0.5%
Polyhexamethylene biguanide 1.0%
Propylene glycol + ethanol 5.0%+5.0%
Fatty acid polyoxyethylene ether-9 0.3%
Cetyl trimethyl ammonium Bromide 3.0%
Disodium hydrogen phosphate-citric acid buffer system pH of 3.0 to 5.0
Sterilized water Make up to the rest
According to the components and the content (w/w), 1.0kg of compound foam type long-acting disinfectant is prepared, and the specific steps are as follows:
(1) introducing nitrogen into part of the sterilized water;
(2) adding propylene glycol and ethanol to the sterilized water and stirring;
(3) adding the decamethyl ammonium bromide and benzalkonium bromide into the system obtained in the step (2) and stirring at a low speed (<150rpm) until complete dissolution;
(4) adding fatty acid polyoxyethylene ether-9 and hexadecyl trimethyl ammonium bromide into the system obtained in the step (3), and stirring at a low speed (<150rpm) for 20min to form a body system A;
(5) introducing nitrogen into another part of the sterilized water;
(6) adding glutaraldehyde and polyhexamethylene biguanide to the sterilized water and stirring at low speed (<150rpm) to dissolve completely;
(7) adding the citric acid and the disodium hydrogen phosphate into the system obtained in the step (6), and stirring at a low speed (<150rpm) until the citric acid and the disodium hydrogen phosphate are completely dissolved; forming a system B;
(8) and transferring the system B into the system A, stirring at a low speed (<150rpm) for 20min, metering the balance by using the sterilized water according to the mass, and measuring the pH of the system to be between 3.0 and 5.0.
Example 4 Compound foam type Long-acting disinfectant containing citric acid
The formulation is shown in the following table.
Citric acid 1.0%
Benzalkonium bromide 1.0%
Decyl methyl ammonium bromide 2.0%
Glutaraldehyde 0.5%
Polyhexamethylene biguanide 1.0%
Propylene glycol 7.5%
Fatty acid polyoxyethylene ether-9 0.25%
Decyl glucoside 1.0%
Sodium citrate-citric acid buffer system pH of 3.0 to 5.0
Sterilized water Make up to the rest
According to the components and the content (w/w), 1.0kg of compound foam type long-acting disinfectant is prepared, and the specific steps are as follows:
(1) introducing nitrogen into part of the sterilized water;
(2) adding propylene glycol to the sterilized water and stirring;
(3) adding the decamethyl ammonium bromide and benzalkonium bromide into the system obtained in the step (2) and stirring at a low speed (<150rpm) until complete dissolution;
(4) adding fatty acid polyoxyethylene ether-9 and decyl glucoside into the system obtained in the step (3), and stirring at a low speed (<150rpm) for 20min to form a body system A;
(5) introducing nitrogen into another part of the sterilized water;
(6) adding glutaraldehyde and polyhexamethylene biguanide to the sterilized water and stirring at low speed (<150rpm) to dissolve completely;
(7) adding the citric acid and sodium citrate into the system obtained in the step (6), and stirring at a low speed (<150rpm) until the citric acid and the sodium citrate are completely dissolved; forming a system B;
(8) and transferring the system B into the system A, stirring at a low speed (<150rpm) for 20min, metering the volume of the rest sterilized water according to the mass, and measuring the pH value of the system to be 3.0-5.0.
Example 5 Compound foam-type Long-acting disinfectant containing citric acid
The formulation is shown in the following table.
Citric acid 1.0%
Benzalkonium bromide 1.5%
Decyl methyl ammonium bromide 3.0%
Glutaraldehyde 0.5%
Polyhexamethylene biguanide 1.5%
Propylene glycol + ethanol 5.0%+5.0%
Fatty acid polyoxyethylene ether-7 0.25%
Decyl glucoside 3.0%
Dipotassium hydrogen phosphate-citric acid buffer system pH of 3.0 to 5.0
Sterilized water Make up to the rest
According to the components and the content (w/w), 1.0kg of compound foam type long-acting disinfectant is prepared, and the specific steps are as follows:
(1) introducing nitrogen into part of the sterilized water;
(2) adding propylene glycol and ethanol to the sterilized water and stirring;
(3) adding the decamethyl ammonium bromide and benzalkonium bromide into the system obtained in the step (2) and stirring at a low speed (<150rpm) until complete dissolution;
(4) adding fatty acid polyoxyethylene ether-7 and decyl glucoside into the system obtained in the step (3), and stirring at a low speed (<150rpm) for 20min to form a body system A;
(5) introducing nitrogen into another part of the sterilized water;
(6) adding glutaraldehyde and polyhexamethylene biguanide to the sterilized water and stirring at low speed (<150rpm) to dissolve completely;
(7) adding the citric acid and the dipotassium hydrogen phosphate into the system obtained in the step (6), and stirring at a low speed (<150rpm) until the citric acid and the dipotassium hydrogen phosphate are completely dissolved; forming a system B;
(8) and transferring the system B into the system A, stirring at a low speed (<150rpm) for 20min, metering the volume of the rest sterilized water according to the mass, and measuring the pH value of the system to be 3.0-5.0.
Example 6 Effect of Compound foam type Long-acting disinfectant containing citric acid
(1) Research on hog cholera virus killing test
The inactivation rate of the disinfectant on Thiveral-strain classical swine fever virus is measured by a suspension quantitative method after the disinfectant acts for 3min, 5min, 7min, 10min and 15min respectively under different concentrations. As a result, it was found that 1: the 600 diluted compound long-acting foam disinfectant prepared in the specific embodiment 4 acts on classical swine fever virus Thviral strains for 10min, and the inactivation rate can reach 100%. 1: the 500-diluted compound long-acting foam disinfectant acts on the classical swine fever virus Thiviral strain for 3min, the inactivation rate reaches 70.4%, the acting time is prolonged to 7min, and the inactivation rate of the classical swine fever virus Thiviral strain is improved to 95.2%; when the action time is prolonged to 10min, the inactivation rate of the classical swine fever virus Thiviral strain is improved to 100 percent, and the inactivation effect reaches the standard. When the ratio of 1: when the disinfectant is diluted by 400 percent, the disinfectant only acts on the classical swine fever virus Thiveral strain for 3min, and the inactivation rate can reach 100 percent. Therefore, the compound long-acting foam disinfectant has a good effect of killing the classical swine fever virus T strain and has good virus killing performance.
TABLE 5 inactivation of classical swine fever virus T-strain by disinfectant
Figure BDA0003636096500000111
Note: the test conditions are all 20 +/-2 ℃, and the results are the average value of 3 tests; the disinfectant diluent here was standard hard water (WS/T798-.
(2) Experimental study on killing of Newcastle disease virus
Suspension killing test is adopted, and chicken embryo infection method is adopted to determine the inactivation rate of the disinfectant on LaSota strain Newcastle disease virus after respectively acting for 5min, 10min and 15min under different concentrations. As a result, it was found that the disinfectant prepared in specific example 4 was diluted up to 1: when 400 hours, the shortest action time is 5min, the inactivation rate of the LaSota strain of the Newcastle disease virus is 100 percent, the LaSota strain acts for 10min and 15min along with the extension of the action time, the inactivation rate is stably kept at 100 percent, and when the inactivation rate is lower than the concentration, the effect is not good. The dilution ratio of the compound long-acting foam disinfectant is 1: has good disinfection effect on the Newcastle disease virus LaSota strain at 400 ℃.
TABLE 6 inactivating effect of disinfectant on Newcastle disease virus
Figure BDA0003636096500000112
Figure BDA0003636096500000121
Note: the disinfectant diluent here was standard hard water (WS/T798-.
(3) Research on clinical natural bacteria surface on-site disinfection effect
According to the requirements of 'veterinary disinfectant identification technical specification', more than 4 animal houses of two livestock and poultry farms which do not use any disinfectant within 1 month are selected to be carried out, and the area of the houses is not less than 50m 2 . The device is used for carrying out a field disinfection effect test of the disinfectant.
TABLE 7 grouping of clinical trials
Figure BDA0003636096500000122
Each experimental colony house was pre-mapped with 3 sampling sites (5X 5 cm) 2 Ground, railing, trough) each site sampled 3 times, the sampling site was adjacent but not the same. Soaking sterilized cotton swab in neutralizer, and placing in a place with area of 5 × 5cm 2 And (3) wiping 10 times horizontally, vertically and forcibly in the area, continuously converting the wiping surface of the swab, cutting the cotton end of the swab into a 10ml sterile centrifugal tube, sealing and marking. Sampling is carried out before disinfection and 30min, 60min and 90min after disinfection respectively. And (3) after the sample is taken back to a laboratory, respectively adding 2ml of sterile normal saline, swirling for 1min, fully eluting as much as possible, then diluting to a proper concentration by using normal saline in a gradient manner, performing bacterial colony counting in an LB culture dish containing 5% calf serum by using a bacterial colony technique, and calculating the sterilization rate.
TABLE 8 killing effect of disinfectant on clinical natural bacteria
Figure BDA0003636096500000123
The result shows that the sterilization effect of the compound long-acting foam disinfectant prepared in the specific embodiment 4 on the ground, the trough and the railing in the livestock and poultry housing is increased along with the increase of the concentration, and the medium concentration can meet the requirement that the clinical sterilization reaches 90%. Compared with a control drug group, the sterilization is more durable and the effect is more obvious.
The disinfection effect can be realized by other specific embodiments provided by the invention.
(4) Disinfectant safety evaluation test
Safety evaluations of examples were carried out in the GLP laboratory, including oral acute toxicity tests in rats, acute skin irritation tests in rabbits, and acute eye irritation tests in rabbits.
SD rats were used to evaluate the acute oral toxicity of the disinfectant in the examples, according to the guidelines for acute toxicity (LD50 assay) in veterinary medicine. 10 SD rats (female and male halves) were orally and gastronasally infected with 1009mg/kg b.w., 1453mg/kg b.w., 2093mg/kg b.w., 3014mg/kg b.w., 4340mg/kg b.w., 6250mg/kg b.w., and 9000mg/kg b.w., respectively. Body weights were taken on day of exposure (day 0), day 7 and day 14. Detailed symptom observations were made before and about 20 minutes, 2 hours, and 4 hours after the infection on day 0, and once a day from day 1 to day 14. All infected animals were dissected gross.
Referring to the Disinfection Specification (2002 edition), Rabbit acute skin irritation/corrosivity test was carried out on disinfectant using Japanese white rabbit as test animal. 3 male rabbits were used for the test, and 0.5mL of the test sample stock solution was evenly spread on the right skin of the back of 3 animals per day, the left skin was used as a control, the test sample was not added, and the exposure time was 4 h. The application is carried out once a day for 14 d. Clinical observations were made once daily 1 day before and 1 day after each application for 24 h. Skin reactions at the sites of administration of the test samples were observed 24h after each day of administration and scored according to skin irritation response scoring criteria.
Referring to the Disinfection technical Specification (2002 edition), Japanese white rabbits were used as test animals to perform rabbit acute eye irritation/corrosion tests on disinfectant. 3 male rabbits were used for the test, each animal was given 0.1mL of test sample in the right eye and control in the left eye. Clinical observation is carried out once a day after infection. Eye examination was performed at 1h, 24h, 48h, 72h post-exposure, and the "mean score" for each animal was calculated for each animal in terms of corneal damage, iris damage, conjunctival hyperemia, and conjunctival edema at different observation times (24h, 48h, 72h) (i.e., the sum of the scores for 24h, 48h, 72h for each animal divided by the number of observations 3). The stimulation intensity of the test sample to the eyes is judged according to the grading standard of the eye stimulation response by respectively carrying out the average scores and the recovery time of the cornea, iris and conjunctiva congestion and edema of the eyes of the animals.
The results were as follows:
TABLE 9 disinfectant safety evaluation test results
Figure BDA0003636096500000131
Figure BDA0003636096500000141
Note: LD (laser diode) 50 Is half-lethal, in units of: mg/kg b.w.
In oral acute toxicity tests, no death was observed in all of the first to fifth groups of animals in the examples, some of the examples began with death in the sixth group (6250mg/kg b.w.), and the half-fatality rate of the disinfectant in examples 2-5 was greater than 5000mg/kg b.w. for both female and male mice, calculated based on the 95% confidence interval, indicating that the disinfectant was non-toxic.
In skin irritation, all test animals showed no skin damage after 14 consecutive days of exposure, indicating no skin irritation.
In the eye irritation test, after 24h, 48h and 72h of infection, corneal lesion, iris lesion, conjunctival congestion and conjunctival edema of the right eye of all test animals are not seen, which indicates that no eye irritation exists.

Claims (10)

1. A compound foam type long-acting disinfectant containing citric acid comprises the following components in percentage by mass:
Figure FDA0003636096490000011
2. the compound foam type long-acting disinfectant containing citric acid according to claim 1, wherein: the compound foam type long-acting disinfectant containing citric acid comprises the following components in percentage by mass:
Figure FDA0003636096490000012
3. the compound foam type long-acting disinfectant containing citric acid according to claim 1 or 2, wherein:
the ratio of the mass of the glutaraldehyde to the sum of the masses of the benzalkonium bromide and the decamethylammonium bromide is 1: 2 or more, preferably 1: (2-4);
the mass ratio of the benzalkonium bromide to the decamethyl bromide is 1: (1-4), preferably 1: (1-3);
the cosolvent is selected from one or more of alcohol solvents containing 2-10 carbon atoms;
the penetrating agent is selected from one or more of ethanol, glycerol trioleate, tricaprylin, fatty acid polyoxyethylene ether-9, fatty acid polyoxyethylene ether-7 and fatty acid polyoxyethylene ether-5;
the foam emulsifier is selected from one or a mixture of dodecyl dimethyl amine oxide, decyl glucoside, coconut oil diethanolamide and hexadecyl trimethyl ammonium bromide;
the stabilizer is selected from salts capable of forming a buffer system with citric acid, including citrate, disodium hydrogen phosphate, dipotassium hydrogen phosphate or sodium hydrogen phosphate.
4. A compound foam type long-acting disinfectant containing citric acid according to any one of claims 1-3, wherein: the compound foam type long-acting disinfectant containing citric acid can kill pathogenic microorganisms including bacteria, viruses, mycoplasma, spores and fungi in the livestock breeding environment.
5. A method for preparing a long-acting disinfectant of the citric acid-containing compound foam type according to any one of claims 1 to 4, comprising the steps of:
(1) introducing nitrogen into part of the sterilized water;
(2) adding the cosolvent into the sterilized water treated in the step (1) and stirring;
(3) adding the decamethyl ammonium bromide and the benzalkonium bromide into the system obtained in the step (2) and stirring at a low speed until the decamethyl ammonium bromide and the benzalkonium bromide are completely dissolved;
(4) adding the penetrant and the foam emulsifier into the system obtained in the step (3) and stirring at a low speed to form a system A;
(5) introducing nitrogen into another part of the sterilized water;
(6) adding the glutaraldehyde and the polyhexamethylene biguanide into the sterilized water treated in the step (5) and stirring at a low speed until the glutaraldehyde and the polyhexamethylene biguanide are completely dissolved;
(7) adding the citric acid and the stabilizing agent into the system obtained in the step (6), and stirring at a low speed (<150rpm) until the citric acid and the stabilizing agent are completely dissolved; forming a system B;
(8) and transferring the system B into the system A, uniformly stirring at a low speed, metering the volume to 100% by mass by using the sterilized water, and keeping the pH value of the system between 3.0 and 5.0.
6. The method of claim 5, wherein: the rotating speed of the low-speed stirring is less than 150 rpm; in the step (4), the stirring time is 20-60 min.
7. The use of a long-acting disinfectant of the citric acid-containing syntactic foam type according to any one of claims 1 to 4, characterized in that: the compound foam type long-acting disinfectant containing the citric acid is diluted by 100-fold and 200-fold with water and is used for disinfecting the environment or objects.
8. Use according to claim 7, characterized in that: the environment is a livestock and poultry breeding environment, and the object is an object in the livestock and poultry breeding environment.
9. A disinfectant composition comprises citric acid, benzalkonium bromide, decamethylammonium bromide, glutaraldehyde and polyhexamethylene biguanide.
10. The disinfectant composition according to claim 9, wherein: the ratio of the mass of the glutaraldehyde to the sum of the masses of the benzalkonium bromide and the decamethylammonium bromide is 1: 2 or more, preferably 1: (2-4);
the mass ratio of the benzalkonium bromide to the decamethyl bromide is 1: (1-4), preferably 1: (1-3);
the mass ratio of the polyhexamethylene biguanide to the glutaraldehyde is 1: (0.5-5), preferably 1: (1-3);
the mass ratio of the citric acid to the glutaraldehyde is 1: (1-10), preferably 1: (1-8).
CN202210502856.3A 2022-05-10 2022-05-10 Compound foam type long-acting disinfectant containing citric acid and preparation method and application thereof Pending CN114916544A (en)

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