A compound foam-type long-acting disinfectant containing citric acid, and its preparation method and application

Abstract

The present invention discloses a compound foam-type long-acting disinfectant containing citric acid, its preparation method and application. The disinfectant includes the following components by weight percentage: citric acid 0.5% to 5.0%, benzalkonium bromide 0.5% to 5.0%, decanium bromide 0.5% to 5.0%, glutaraldehyde 0.25% to 2.5%, polyhexamethylene biguanide 0.5% to 5.0%, cosolvent 3.0% to 15.0%, penetrant 0.1% to 0.5%, foam emulsifier 0.5% to 5.0%, stabilizer and citric acid can form a buffer system, maintain a pH value of 3.0 to 5.0, and sterile water is supplemented to 100%. The compound disinfectant of the present invention has a synergistic or additive effect, killing all pathogenic microorganisms of animal origin including bacteria, viruses, mycoplasmas, fungi, etc. in the breeding environment, with a sterilization efficiency of 100%.

Description

Technical Field

[0001] The invention belongs to the field of biosafety protection products 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 Art

[0002] Major livestock and poultry epidemics not only severely harm the development of the livestock and poultry industry but also pose a constant threat to human health and public health. Strengthening the prevention and control of major animal and foreign animal epidemics is essential to ensuring the safe supply of livestock and poultry products and national biosecurity.

[0003] Biosafety control products play a vital role in disease prevention and control, and disinfectants are a key component. However, existing biosafety control products have significant challenges, including low sterilization efficiency, poor safety, and poor durability, and lack breakthrough innovative technologies.

[0004] Problem 1: Low sterilization efficiency

[0005] Currently, animal pathogenic microorganisms present in aquaculture environments include bacteria, viruses, mycoplasmas, fungi, etc., and it is often not possible for a single disinfectant product to effectively kill all pathogenic microorganisms. Commonly used quaternary ammonium disinfectants are not very effective against bacterial spores and mycoplasmas. Therefore, it is often necessary to formulate a compound disinfectant based on its different bactericidal spectra to solve the problem of low bactericidal efficiency.

[0006] Problem 2: Poor security

[0007] Farm disinfection is an ongoing process with high product consumption. To reduce costs, toxic disinfectants such as caustic soda (the active ingredient is sodium hydroxide), aldehydes (formaldehyde, glutaraldehyde), and phenols (phenol) are often used. This not only harms animals on the farm but also has potential toxic effects on farm workers. There have also been many reports of animal deaths due to excessive or improper use of disinfectants. The development of green, environmentally friendly, and safe disinfectants is extremely necessary.

[0008] Problem 3: Poor durability

[0009] Currently, disinfectants are typically applied as solutions, sprayed onto livestock rails, troughs, or barn floors. Due to the high fluidity of these solutions, they have poor adhesion and durability on irregular surfaces, such as rails and uneven floors, making it difficult for them to fully contact the object. This also results in low sterilization efficiency, requiring increased disinfection frequency and resulting in excessive disinfectant consumption. This problem can be addressed by developing a disinfectant product with a long-lasting foam that increases adhesion and maintains a long-lasting killing effect.

[0010] Therefore, there is an urgent need to develop green, efficient, safe and low-cost biosafety control products, and to promote their industrialization and application to promote the green, sustainable and healthy development of my country's animal husbandry. Summary of the Invention

[0011] In response to the problems existing in the prior art, the present invention provides a compound foam-type long-acting disinfectant containing citric acid, which is environmentally friendly, efficient, low-cost, residue-free, has good bactericidal effect, and is easy to transport, and a preparation method thereof.

[0012] The compound foam-type long-acting disinfectant containing citric acid provided by the present invention comprises the following components in percentage by weight:

[0013] Furthermore, the compound foam-type long-acting disinfectant containing citric acid includes the following components in percentage by mass:

[0014] Preferably, the ratio of the mass of the glutaraldehyde to the sum of the mass of the benzalkonium bromide and the decanium bromide may be 1:2 or above, more preferably 1:(2-4), specifically 1:2 or 1:3 or 1:4;

[0015] Preferably, the mass ratio of benzalkonium bromide to decanium bromide may be 1:(1-4), more preferably 1:(1-3), specifically 1:1 or 1:2 or 1:3 or 1:4;

[0016] Preferably, the cosolvent can be selected from one or more alcohol solvents containing 2-10 carbon atoms, such as one or more mixtures of alcohol solvents such as ethanol, propylene glycol, butanol, isobutanol, and octanol;

[0017] Preferably, the penetrant can be selected from one or more mixtures of ethanol, triolein, tricaprylin, fatty acid polyoxyethylene ether-9, fatty acid polyoxyethylene ether-7, fatty acid polyoxyethylene ether-5, etc.;

[0018] Preferably, the foam emulsifier can be selected from one or more mixtures of dodecyl dimethylamine oxide, decyl glucoside, coconut oil diethanolamide, and cetyl trimethyl ammonium bromide; specifically, the foam emulsifier is decyl glucoside, and its mass content is preferably 1%; the foam emulsifier is coconut oil diethanolamide or cetyl trimethyl ammonium bromide, and its mass content is preferably 3%.

[0019] 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, etc.

[0020] The present invention also provides a method for preparing the compound foam-type long-acting disinfectant containing citric acid.

[0021] The preparation method of the compound foam-type long-acting disinfectant containing citric acid provided by the present invention comprises the following steps:

[0022] (1) introducing nitrogen into a portion of the sterilized water;

[0023] (2) adding the cosolvent to the sterilized water treated in step (1) and stirring;

[0024] (3) adding the decamethyl ammonium bromide and benzalkonium bromide to the system obtained in step (2) and stirring at a low speed (<150 rpm) until completely dissolved;

[0025] (4) adding the penetrant and the foam emulsifier to the system obtained in step (3) and stirring at a low speed (<150 rpm) to form system A;

[0026] (5) taking another portion of the sterilized water and passing nitrogen into it;

[0027] (6) adding the glutaraldehyde and polyhexamethylene biguanide to the sterilized water treated in step (5) and stirring at a low speed (<150 rpm) until completely dissolved;

[0028] (7) adding the citric acid and stabilizer to the system obtained in step (6) and stirring at a low speed (<150 rpm) until completely dissolved to form system B;

[0029] (8) Transfer system B into system A, stir evenly at a low speed (<150 rpm), and dilute to 100% by mass with the sterilized water, maintaining the pH value of the system between 3.0 and 5.0.

[0030] In the above method, the rotation speed of the low-speed stirring is <150 rpm.

[0031] In step (4) of the above method, the stirring time may be 20-60 minutes.

[0032] The citric acid-containing compound foam-type long-acting disinfectant provided by the present invention can effectively kill common pathogenic microorganisms such as bacteria, viruses, mycoplasma, spores, fungi, etc. on the ground, railings, feeding troughs, etc. in animal husbandry environments.

[0033] The virus can specifically be classical swine fever virus (such as Thiveral strain classical swine fever virus), Newcastle disease virus (such as LaSota strain Newcastle disease virus), etc.

[0034] The spores are specifically Bacillus subtilis.

[0035] The present invention also protects a disinfectant composition.

[0036] The disinfectant composition protected by the present invention comprises citric acid, benzalkonium bromide, decanium bromide, glutaraldehyde and polyhexamethylene biguanide.

[0037] wherein the ratio of the mass of the glutaraldehyde to the sum of the masses of the benzalkonium bromide and the decanium methyl bromide is 1:2 or greater, preferably 1:(2-4);

[0038] The mass ratio of the benzalkonium bromide to the decanium bromide is 1:(1-4), preferably 1:(1-3);

[0039] The mass ratio of polyhexamethylene biguanide to glutaraldehyde is 1:(0.5-5), preferably 1:(1-3);

[0040] The mass ratio of the citric acid to glutaraldehyde is 1:(1-10), preferably 1:(1-8).

[0041] To address the problem of low sterilization efficiency of current disinfectants, the present invention provides a compound formula that works synergistically to effectively solve the problem of low sterilization efficiency of a single formula. The functions of each component in the formula are analyzed as follows:

[0042] 1. Benzalkonium bromide and decanium bromide are two cationic surfactants that accumulate on the cell wall surface, thereby interfering with the filtration function of the microbial cell membrane, increasing the permeability of bacterial cells, allowing water to penetrate into the bacteria and causing substance leakage, affecting bacterial metabolism and thus destroying the cell structure, ultimately leading to bacterial death. This type of disinfectant has low toxicity.

[0043] It has strong decontamination ability, is non-corrosive to metal materials, has a synergistic bactericidal effect, and has good killing ability against common animal-derived bacteria, but has poor effect on bacterial spores.

[0044] 2. The killing effect of glutaraldehyde on microorganisms mainly depends on the aldehyde group, which mainly acts on the sulfhydryl, hydroxyl, carboxyl and amino groups of bacterial proteins, causing them to alkylate, causing protein coagulation and bacterial death. It has a good killing effect on microorganisms such as viruses, bacterial spores, fungi and their spores.

[0045] 3. Polyhexamethylene biguanide is an environmentally friendly disinfectant. The guanidine group has high activity and can make the polymer positively charged. It is easily adsorbed by various negatively charged bacteria, thereby inhibiting the division function of bacteria and causing them to lose their reproductive ability.

[0046] 4. Citric acid, also known as citric acid, has a molecular formula of C6H8O7. It is an important organic acid. It is a colorless crystal, odorless, has a strong sour taste, is easily soluble in water, and can be used as a pH regulator. In the inventor's preliminary experimental research, it was found that it has a good killing effect on animal-derived mycoplasma at a relatively low concentration (0.5% to 1.0%).

[0047] The test results show that the above ingredients can work together to kill all pathogenic microorganisms of animal origin in the breeding environment, including bacteria, viruses, mycoplasma, fungi, etc., with a sterilization efficiency of 100%.

[0048] To address the problem of poor sterilization safety of current disinfectants, the present invention addresses the problem that glutaraldehyde, an aldehyde product, has certain irritation and corrosiveness. However, due to the synergistic effect of the two, the concentration of glutaraldehyde in the compound is reduced by more than 60% to 80% compared with that of the single formula. Toxicity test results show that the product of this formula is safe, effective and non-irritating.

[0049] To address the problem of poor sterilization durability of current disinfectants, the present invention's formulation contains a penetrant (SF), a solubilizer, a stabilizer, and a foaming agent, particularly polyhexamethylene biguanide, a high molecular weight polymer. This product forms a high molecular weight solution that easily adsorbs various negatively charged bacteria. During use, a foaming gun or foaming machine forms rich foam that adheres to the surface of the object being disinfected, achieving a long-lasting and durable disinfection effect.

[0050] Compared with the prior art, the present invention has the following beneficial effects:

[0051] (1) Wide sterilization range. Due to the synergistic or additive effects of the compounded disinfectants, the total sterilization ability of the compound is enhanced. Quaternary ammonium salts alone generally cannot kill bacterial spores, while aldehyde disinfectants have a good effect on killing bacterial spores. The present invention uses quaternary ammonium salts, aldehydes, acids and guanidine compounds to synergistically kill all pathogenic microorganisms of animal origin in the breeding environment, including bacteria, viruses, mycoplasmas, fungi, etc., with a sterilization efficiency of 100%.

[0052] (2) Long-lasting and durable. The present invention comprises a penetrant, a cosolvent, a stabilizer, and a foaming agent, particularly polyhexamethylene biguanide, which is a high molecular weight polymer. The product is formed into a high molecular weight solution state, which is easily adsorbed by various negatively charged bacteria. When used, a foaming gun or foaming machine forms rich foam, which adheres to the surface of the disinfected object, achieving a long-lasting and durable disinfection effect. Compared with the prior art, the amount of disinfectant used can be saved.

[0053] (3) High safety. Aldehyde disinfectants are skin irritants and acutely toxic. In the present invention, through effective synergistic combination, the amount of glutaraldehyde used is greatly reduced to only 20% of the original amount, and it has no toxic side effects on the human body. Animal toxicology tests have shown that the formula is highly effective, safe, and non-toxic.

[0054] (4) It can effectively kill mycoplasmas. Mycoplasmas, as pathogens, have the ability to spread vertically, horizontally, and mechanically. Their infection pathways are also complex and diverse. They survive extensively in the aquaculture environment by attaching to organic biomass. Compared with the existing technology, the present invention can effectively kill mycoplasmas in the aquaculture environment, playing an important role in effectively controlling the spread of mycoplasma disease in farms.

[0055] (5) The production process is simple, stable, easy to scale up, and has significant on-site disinfection effects, making it highly valuable for promotion. DETAILED DESCRIPTION

[0056] The present invention is further described below with reference to specific examples, but the present invention is not limited to the following examples. The methods described are conventional methods unless otherwise specified. The raw materials described can be obtained from public commercial channels unless otherwise specified.

[0057] Example 1

[0058] (1) Co-screening of glutaraldehyde and quaternary ammonium salt content

[0059] Glutaraldehyde and decanediamine bromide and benzalkonium bromide raw materials were restored to room temperature, where the ratio (mass ratio) of decanediamine bromide and benzalkonium bromide was 1:1. PBS solution was used as the solvent. Different disinfectant groups were prepared according to Table 1. Bacillus subtilis CMCC (B) 63501 was used as the indicator bacteria. A suspension quantitative bactericidal test was carried out, and the bactericidal rate was used as the screening basis.

[0060] Table 1 Glutaraldehyde and quaternary ammonium salt ratio test results

[0061]

[0062]

[0063] Note: The above results are the average of three tests; the test conditions are 20±2℃; the disinfectant is diluted 1:2 and the action time is 1h.

[0064] The results showed that in Group 8, the quaternary ammonium salt alone had a very low spore-killing ability (7.8%). When 1% glutaraldehyde was mixed with a quaternary ammonium salt solution at a concentration of 0.1%-4%, the sterilization rate increased with increasing quaternary ammonium salt content. The test results showed that when the glutaraldehyde:quaternary ammonium salt ratio was equal to or greater than 1:2, the sterilization rate could reach greater than 99.90%, indicating satisfactory disinfection results.

[0065] (2) Collaborative screening of two quaternary ammonium salt contents

[0066] Glutaraldehyde, decanium bromide, and benzalkonium bromide APIs were returned to room temperature. Experimental disinfectant mixtures were prepared according to Table 2 and grouped. Suspension quantitative bactericidal tests were conducted using Bacillus subtilis 63501 as the indicator bacteria. The results are as follows:

[0067] Table 2 benzalkonium bromide and decylmethyl ammonium bromide ratio test results

[0068]

[0069] Note: The above results are the average of 3 tests; the test conditions are 20±1℃; the disinfectant is diluted 1:2 and the action time is 1h.

[0070] The results showed that, at a constant total content of 1% glutaraldehyde and 2% quaternary ammonium salt, the sterilization rate increased with the increase in the ratio of decanalkonium bromide to benzalkonium bromide. When the sterilization ratio of decanalkonium bromide to benzalkonium bromide was 1:1, the sterilization rate was 99.92%, when it was 2:1, the sterilization rate was 99.98%, and when it was 3:1, the sterilization rate was 100%, indicating that the disinfection effect was qualified.

[0071] (3) Collaborative screening of polyhexamethylene biguanide content

[0072] The polyhexamethylene biguanide content was screened, and the experimental disinfectant mixtures were prepared and divided into groups according to Table 3. A suspension quantitative bactericidal test was conducted using Bacillus subtilis 63501 as the indicator bacteria. The results are as follows:

[0073] Table 3 Polyhexamethylene biguanide ratio test results (%)

[0074]

[0075]

[0076] The results showed that when the polyhexamethylene biguanide content was between 0.5% and 1.5%, the bactericidal rate of each group was greater than 99.9%, and the disinfection effect was qualified.

[0077] (4) Collaborative screening of citric acid content

[0078] The citric acid content was screened, and the experimental disinfectant mixtures were prepared and divided into groups according to Table 4. A suspension quantitative bactericidal test was conducted using 10 clinical bovine Mycoplasma pathogens (BS1738-BS1748) as indicator bacteria. The results are as follows:

[0079] Table 4 Screening results of citric acid content in the system (%)

[0080]

[0081] The results showed that when the citric acid content was between 0.5% and 4.0%, the bactericidal rate of each group was greater than 99.9%, and the disinfection effect was qualified.

[0082] (5) Foam emulsifier screening

[0083] Coconut oil diethanolamide, decyl glucoside, and cetyl trimethyl ammonium bromide emulsifiers were screened at concentrations ranging from 1% to 3%. The test results showed that 1% decyl glucoside produced a rich, smooth foam that lasted up to 60 minutes. However, 1% coconut oil diethanolamide and 1% cetyl trimethyl ammonium bromide produced a thin, short-lived foam, which completely dissipated after 60 minutes. 3% coconut oil diethanolamide and 3% cetyl trimethyl ammonium bromide met the requirement for a foam that lasted up to 60 minutes.

[0084] Example 2: Compound foam-type long-acting disinfectant containing citric acid

[0085] The composition of the prescription is shown in the following table.

[0086]

[0087]

[0088] According to the above components and contents (w / w), 1.0 kg of compound foam-type long-acting disinfectant is prepared. The specific steps are as follows:

[0089] (1) introducing nitrogen into a portion of the sterilized water;

[0090] (2) adding propylene glycol to the sterilized water and stirring;

[0091] (3) adding the decamethyl ammonium bromide and benzalkonium bromide to the system obtained in step (2) and stirring at a low speed (<150 rpm) until completely dissolved;

[0092] (4) adding fatty acid polyoxyethylene ether-9 and decyl glucoside to the system obtained in step (3) and stirring at a low speed (<150 rpm) for 20 min to form system A;

[0093] (5) taking another portion of the sterilized water and passing nitrogen into it;

[0094] (6) adding glutaraldehyde and polyhexamethylene biguanide to the sterilized water and stirring at a low speed (<150 rpm) until completely dissolved;

[0095] (7) adding the citric acid and sodium citrate to the system obtained in step (6) and stirring at a low speed (<150 rpm) until completely dissolved to form system B;

[0096] (8) System B was transferred into system A and stirred at low speed (<150 rpm) for 20 min. The remaining volume was made up by mass with the sterilized water. The pH of the system was measured to be between 3.0 and 5.0.

[0097] Example 3: Compound Foam-Type Long-Acting Disinfectant Containing Citric Acid

[0098] The composition of the prescription is shown in the following table.

[0099] Citric acid 0.5％ Benzalkonium bromide 1.5％ Decylmethylammonium bromide 3.0％ Glutaraldehyde 0.5％ Polyhexamethylene biguanide 1.0％ Propylene glycol + ethanol 5.0％+5.0％ Fatty acid polyoxyethylene ether-9 0.3％ Cetyltrimethylammonium bromide 3.0％ Disodium hydrogen phosphate-citric acid buffer system pH between 3.0 and 5.0 sterile water Replenish to balance

[0100] According to the above components and contents (w / w), prepare 1.0 kg of compound foam-type long-acting disinfectant. The specific steps are as follows:

[0101] (1) introducing nitrogen into a portion of the sterilized water;

[0102] (2) adding propylene glycol and ethanol to the sterilized water and stirring;

[0103] (3) adding the decamethylammonium bromide and benzalkonium bromide to the system obtained in step (2) and stirring at a low speed (<150 rpm) until completely dissolved;

[0104] (4) adding fatty acid polyoxyethylene ether-9 and cetyltrimethylammonium bromide to the system obtained in step (3) and stirring at a low speed (<150 rpm) for 20 min to form system A;

[0105] (5) taking another portion of the sterilized water and passing nitrogen into it;

[0106] (6) adding glutaraldehyde and polyhexamethylene biguanide to the sterilized water and stirring at a low speed (<150 rpm) until completely dissolved;

[0107] (7) adding the citric acid and disodium hydrogen phosphate to the system obtained in step (6) and stirring at a low speed (<150 rpm) until completely dissolved to form system B;

[0108] (8) System B was transferred into system A and stirred at low speed (<150 rpm) for 20 min. The remaining volume was made up by mass with the sterilized water. The pH of the system was measured to be between 3.0 and 5.0.

[0109] Example 4: Compound Foam-Type Long-Acting Disinfectant Containing Citric Acid

[0110] The composition of the prescription is shown in the following table.

[0111] Citric acid 1.0％ Benzalkonium bromide 1.0％ Decylmethylammonium 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 between 3.0 and 5.0 sterile water Replenish to balance

[0112] According to the above components and contents (w / w), prepare 1.0 kg of compound foam-type long-acting disinfectant. The specific steps are as follows:

[0113] (1) introducing nitrogen into a portion of the sterilized water;

[0114] (2) adding propylene glycol to the sterilized water and stirring;

[0115] (3) adding the decamethyl ammonium bromide and benzalkonium bromide to the system obtained in step (2) and stirring at a low speed (<150 rpm) until completely dissolved;

[0116] (4) adding fatty acid polyoxyethylene ether-9 and decyl glucoside to the system obtained in step (3) and stirring at a low speed (<150 rpm) for 20 min to form system A;

[0117] (5) taking another portion of the sterilized water and passing nitrogen into it;

[0118] (6) adding glutaraldehyde and polyhexamethylene biguanide to the sterilized water and stirring at a low speed (<150 rpm) until completely dissolved;

[0119] (7) adding the citric acid and sodium citrate to the system obtained in step (6) and stirring at a low speed (<150 rpm) until completely dissolved to form system B;

[0120] (8) Transfer system B into system A and stir at low speed (<150 rpm) for 20 min. The remaining volume is made up by mass with the sterilized water. The pH of the system is measured to be between 3.0 and 5.0.

[0121] Example 5: Compound Foam-Type Long-Acting Disinfectant Containing Citric Acid

[0122] The composition of the prescription is shown in the following table.

[0123] Citric acid 1.0％ Benzalkonium bromide 1.5％ Decylmethylammonium 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 between 3.0 and 5.0 sterile water Replenish to balance

[0124] According to the above components and contents (w / w), 1.0 kg of compound foam-type long-acting disinfectant is prepared. The specific steps are as follows:

[0125] (1) introducing nitrogen into a portion of the sterilized water;

[0126] (2) adding propylene glycol and ethanol to the sterilized water and stirring;

[0127] (3) adding the decamethyl ammonium bromide and benzalkonium bromide to the system obtained in step (2) and stirring at a low speed (<150 rpm) until completely dissolved;

[0128] (4) adding fatty acid polyoxyethylene ether-7 and decyl glucoside to the system obtained in step (3) and stirring at a low speed (<150 rpm) for 20 min to form system A;

[0129] (5) taking another portion of the sterilized water and passing nitrogen into it;

[0130] (6) adding glutaraldehyde and polyhexamethylene biguanide to the sterilized water and stirring at a low speed (<150 rpm) until completely dissolved;

[0131] (7) adding the citric acid and dipotassium hydrogen phosphate to the system obtained in step (6) and stirring at a low speed (<150 rpm) until completely dissolved to form system B;

[0132] (8) System B was transferred into system A and stirred at low speed (<150 rpm) for 20 min. The remaining volume was made up by mass with the sterilized water. The pH of the system was measured to be between 3.0 and 5.0.

[0133] Example 6: Implementation Effect of Compound Foam-Type Long-Acting Disinfectant Containing Citric Acid

[0134] (1) Experimental study on killing of swine fever virus

[0135] Using a suspension quantitative method, the inactivation rates of the disinfectant against the Thiveral strain of classical swine fever virus were determined at different concentrations for 3, 5, 7, 10, and 15 minutes. The results showed that the compound long-acting foam disinfectant prepared in Specific Example 4, diluted 1:600, achieved a 100% inactivation rate against the Thiveral strain of classical swine fever virus after a 10-minute exposure. The compound long-acting foam disinfectant, diluted 1:500, achieved a 70.4% inactivation rate against the Thiveral strain of classical swine fever virus after a 3-minute exposure. When the exposure time was extended to 7 minutes, the inactivation rate increased to 95.2%. When the exposure time was extended to 10 minutes, the inactivation rate reached 100%, achieving satisfactory inactivation results. At a 1:400 dilution, the disinfectant achieved a 100% inactivation rate against the Thiveral strain of classical swine fever virus after only 3 minutes. Therefore, the compound long-acting foam disinfectant demonstrated excellent virucidal efficacy against the T strain of classical swine fever virus.

[0136] Table 5 Inactivation effect of disinfectants on swine fever virus T strain

[0137]

[0138] Note: The test conditions are all 20±2℃, and the above results are the average of 3 tests; the disinfectant diluent here is standard hard water (WS / T 798-2022).

[0139] (2) Experimental study on killing Newcastle disease virus

[0140] A suspension killing test was conducted using a chicken embryo infection method to determine the inactivation rates of the disinfectant against the LaSota strain of Newcastle disease virus at different concentrations when exposed to water for 5 minutes, 10 minutes, and 15 minutes, respectively. The results showed that the disinfectant prepared in Specific Example 4 had a 100% inactivation rate against the LaSota strain of Newcastle disease virus at a dilution factor of up to 1:400, with a shortest exposure time of 5 minutes. The inactivation rate remained stable at 100% with prolonged exposure time, at 10 minutes and 15 minutes. The effect was poor at concentrations below these limits. The compound long-acting foam disinfectant had a good disinfection effect against the LaSota strain of Newcastle disease virus when exposed to water for a dilution factor of 1:400.

[0141] Table 6 Inactivation effect of disinfectants on Newcastle disease virus

[0142]

[0143]

[0144] Note: The disinfectant dilution liquid here is standard hard water (WS / T 798-2022).

[0145] (3) Study on the effect of on-site disinfection of clinical natural bacteria surfaces

[0146] According to the requirements of the Technical Specifications for the Identification of Veterinary Disinfectants, at least four animal pens in two livestock and poultry farms that have not used any disinfectants within one month were selected for the test, and the average area of ​​the pens should not be less than 50m 2 . Used to conduct on-site disinfection effect tests of disinfectants.

[0147] Table 7 Clinical trial groups

[0148]

[0149] Three sampling sites (5×5 cm 2 Each part was sampled 3 times, and the sampling sites were adjacent but not the same. A sterile cotton swab was soaked with a neutralizer and swabbed on an area of ​​5 × 5 cm 2 Wipe the area vigorously 10 times vertically and horizontally, constantly switching the swab side. Cut the cotton end of the swab and place it in a 10ml sterile centrifuge tube, seal, and label. Sampling should be performed before disinfection and 30, 60, and 90 minutes after disinfection. Once the sample is returned to the laboratory, add 2ml of sterile saline solution to each tube and vortex for 1 minute to fully elute it. Then, dilute the sample to the appropriate concentration using a gradient of saline. Culture the sample in an LB dish containing 5% calf serum, count the colonies, and calculate the bactericidal rate.

[0150] Table 8 Killing effect of disinfectants on clinical natural bacteria

[0151]

[0152] The results showed that the compound long-lasting foam disinfectant prepared in Example 4 had a greater bactericidal effect on the floor, troughs, and railings in livestock and poultry pens as the concentration increased, and a moderate concentration was sufficient to meet the clinical requirement of achieving a 90% bactericidal rate. Compared with the control drug group, the bactericidal effect was more sustained and more significant.

[0153] Other specific embodiments provided by the present invention can all achieve the above disinfection effects.

[0154] (4) Disinfectant safety evaluation test

[0155] The safety evaluation of the examples was carried out in the GLP laboratory, including an acute oral toxicity test in rats, an acute skin irritation test in rabbits, and an acute eye irritation test in rabbits.

[0156] With reference to the Guidelines for Acute Toxicity of Veterinary Drugs (LD50 Determination), SD rats were used to evaluate the acute oral toxicity of the disinfectants in the examples. Ten SD rats (half male and half female) were orally gavaged with the drug at doses of 1009 mg / kg bw, 1453 mg / kg bw, 2093 mg / kg bw, 3014 mg / kg bw, 4340 mg / kg bw, 6250 mg / kg bw, and 9000 mg / kg bw. The rats were weighed before infection on the day of infection (Day 0), on the 7th day, and on the 14th day. Detailed symptom observations were conducted before infection on Day 0, approximately 20 minutes, 2 hours, and 4 hours after infection, and symptoms were observed once a day from Day 1 to Day 14. Gross autopsy was performed on all infected animals.

[0157] With reference to the Technical Specifications for Disinfection (2002 edition), Japanese white rabbits were used as test animals to conduct an acute skin irritation / corrosion test on the disinfectant. Three male rabbits were used for the test. Every day, 0.5 mL of the test sample solution was evenly applied to the skin on the right side of the back of the three animals. The left skin was used as a control without the test sample. The exposure time was 4 hours. Apply once a day for 14 consecutive days. Clinical observations were performed once a day before administration and on the first day of administration, and then clinical observations were performed 24 hours after each application. The skin reaction at the test sample site was observed 24 hours after administration every day and scored according to the skin irritation reaction scoring standard.

[0158] In accordance with the "Technical Specifications for Disinfection" (2002 edition), Japanese white rabbits were used as test animals for acute eye irritation / corrosion testing of the disinfectant in rabbits. Three male rabbits were used for the test, with 0.1 mL of the test sample administered to the right eye of each animal, and the left eye served as a control. Clinical observations were conducted daily after exposure. Eye examinations were performed 1, 24, 48, and 72 hours after exposure. The "average score" for corneal damage, iris damage, conjunctival congestion, and conjunctival edema at each observation time (24, 48, and 72 hours) was calculated for each animal (i.e., the sum of the 24, 48, and 72 hour scores for each animal divided by the number of observations, 3). The average scores for corneal, iris, and conjunctival congestion and edema, as well as the recovery time, were used to determine the eye irritation intensity of the test sample according to the eye irritation response grading standard.

[0159] Here are the results:

[0160] Table 9 Disinfectant safety evaluation test results

[0161]

[0162]

[0163] Note: LD 50 The median lethality rate is mg / kg bw.

[0164] In the oral acute toxicity test, no deaths were observed in animals from Groups 1 to 5 in all examples. In some examples, animal deaths occurred starting from Group 6 (6250 mg / kg bw). Based on the 95% confidence interval, the median lethality of the disinfectants in Examples 2 to 5 for female and male mice was greater than 5000 mg / kg bw, indicating that the disinfectants were non-toxic.

[0165] Regarding skin irritation, all test animals showed no skin damage after 14 consecutive days of exposure, indicating no skin irritation.

[0166] In the eye irritation test, all test animals showed no corneal damage, iris damage, conjunctival congestion or conjunctival edema in the right eye 24h, 48h and 72h after exposure, indicating no eye irritation.

Claims

1. A compound foam-type long-acting disinfectant containing citric acid, comprising the following components in percentage by weight: Citric acid 1.0%; Benzalkonium bromide 1.0%; Decylmethylammonium 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 and citric acid form a buffer system to maintain a pH value of 3.0-5.0; Make up to 100% with sterile water.

2. The use of the compound foam type long-acting disinfectant containing citric acid according to claim 1, characterized in that: The compound foam-type long-acting disinfectant containing citric acid can kill pathogenic microorganisms in animal husbandry environments, and the microorganisms include bacteria, viruses, mycoplasmas or fungi.

3. The method for preparing the compound foam-type long-acting disinfectant containing citric acid according to claim 1, comprising the following steps: (1) introducing nitrogen into a portion of the sterilized water; (2) adding the propylene glycol to the sterilized water treated in step (1) and stirring; (3) adding the decanium bromide and benzalkonium bromide to the system obtained in step (2) and stirring at a low speed until they are completely dissolved; (4) adding the fatty acid polyoxyethylene ether-9 and the decyl glucoside to the system obtained in step (3) and stirring at a low speed to form a system A; (5) Add nitrogen to another portion of the sterilized water; (6) adding the glutaraldehyde and the polyhexamethylene biguanide to the sterilized water treated in step (5) and stirring at a low speed until they are completely dissolved; (7) Adding the citric acid and the sodium citrate to the system obtained in step (6) and stirring at a speed of <150 rpm until completely dissolved to form system B; (8) Transfer system B into system A, stir evenly at a low speed, and dilute to 100% by mass with the sterilized water, maintaining the pH value of the system between 3.0 and 5.

0.

4. The preparation method according to claim 3, wherein: The rotation speed of the low-speed stirring is <150 rpm; in the step (4), the stirring time is 20-60 min.

5. The use of the compound foam type long-acting disinfectant containing citric acid according to claim 1, characterized in that: The compound foam-type long-acting disinfectant containing citric acid is diluted 100-200 times with water and used for disinfecting the environment or objects.

6. The use according to claim 5, characterized in that: The environment is a livestock and poultry breeding environment, and the objects are objects in the livestock and poultry breeding environment.

Images