CN111436429A - Pharmaceutical composition for environmental disinfection and preparation method thereof - Google Patents

Abstract

The invention provides a pharmaceutical composition for environmental disinfection and a preparation method thereof, and relates to the field of veterinary disinfectants. The composition comprises 30-200 g of single-chain quaternary ammonium salt and 50-300 g of double-chain quaternary ammonium salt per 1 L , solution stabilizer 0.005 ~ 0.5g, acid-base regulator 0.5 ~ 3g, and the rest are purified water. The composition of the present invention has simple preparation process, low drug cost, good stability and good disinfection effect. The composition of the present invention, wherein the stabilizer is selected from novel and safe stabilizers on the market, and a suitable pH range, the composition of the present invention The pH and the solution stabilizer interact and complement each other to form the stable system of the composition of the present invention, so that the disinfection effect is more durable.

Description

A kind of pharmaceutical composition for environmental disinfection and preparation method thereof

technical field

The invention relates to the field of veterinary disinfectants, in particular to a pharmaceutical composition containing single-chain quaternary ammonium salt and double-chain quaternary ammonium salt for environmental disinfection and a preparation method thereof.

Background technique

In recent years, the successive major animal diseases have not only caused huge economic losses to my country's animal husbandry, but also directly threatened human health. And at present, the occurrence of animal diseases is on the rise.

The prevalence of zoonotic diseases must meet three basic conditions, namely the source of infection, the route of transmission and the susceptible animals, and only when these three conditions exist at the same time and are connected with each other can infectious diseases become popular in animal groups. At present, the control of animal infectious diseases in my country mainly includes three methods: vaccine immunization, drug prevention and control, and environmental disinfection. However, due to the widespread existence of the idea of "emphasizing maintenance and neglecting prevention, and focusing on prevention and treatment", the control of animal infectious diseases mainly relies on vaccine immunization and drug prevention and treatment.

Disinfection is the primary measure to implement the prevention-oriented policy. Disinfectants are usually used to disinfect livestock and poultry (including animal skin and mucous membranes and superficial body cavities) and their surrounding environment to kill pathogens, reduce the pollution of pathogens to the breeding environment, cut off the transmission route of diseases, and prevent the occurrence and spread of diseases. , and then control and eliminate the purpose of infectious diseases. Therefore, thorough and standardized disinfection is the most effective and convenient method to prevent and control diseases. The use of disinfectants to disinfect livestock and poultry and their surrounding environment to kill pathogens has become an important measure to prevent and control the epidemic of livestock and poultry infectious diseases.

The chemical disinfectants currently used are mostly unilateral disinfectants, such as phenol, formaldehyde, ethanol, bleaching powder, etc. However, due to the fact that unilateral veterinary disinfectants often have a narrow disinfection spectrum and a narrow range of use, poor stability, strong corrosiveness, irritation, and toxicity, the disinfection performance is easily affected by other substances, and the price is expensive. certain restrictions. Therefore, it is particularly necessary to develop compound veterinary disinfectants to improve the bactericidal effect and overcome the shortcomings of unilateral veterinary disinfectants. Therefore, in view of the current situation of frequent outbreaks of epidemic diseases in my country's livestock and poultry breeding industry due to poor breeding environment and the weak innovation ability of veterinary disinfectant manufacturers, carry out investigations on avian influenza virus, circovirus, PRRS virus, foot-and-mouth disease virus, chain The research on efficient and safe broad-spectrum compound disinfectant with killing effect on various pathogenic microorganisms such as cocci is an urgent need to ensure the healthy development of animal husbandry in my country and improve people's living standards. Therefore, it is of great significance to develop a pharmaceutical composition for environmental disinfection with good disinfection effect, high stability and long sterilization and disinfection time.

SUMMARY OF THE INVENTION

The object of the present invention is to provide a pharmaceutical composition for environmental disinfection with simple process, good disinfection effect, high stability, long sterilization and disinfection time and low cost. The pharmaceutical composition of the present invention is composed of components such as single-chain quaternary ammonium salt, double-chain quaternary ammonium salt, solution stabilizer, acid-base regulator, etc. The present invention also provides a preparation method of a pharmaceutical composition for environmental disinfection. The composition of the present invention has obvious effect on bacterial viruses such as RNA virus, parvovirus, adenovirus, poliovirus, avian influenza, Newcastle disease, infectious bursa.

Another object of the present invention is to provide a pharmaceutical composition for environmental disinfection that is superior to conventional pharmaceutical compositions for environmental disinfection. The composition uses the composition of disodium EDTA and Provichem 2203 as a solution stabilizer to obtain a pharmaceutical composition for environmental disinfection, compared with a pharmaceutical composition for environmental disinfection obtained by other inventions, the The composition has higher stability and better sterilization and disinfection effect. And select the composition of disodium EDTA and Provichem 2203 as a solution stabilizer to obtain a pharmaceutical composition for environmental disinfection, when the pH value of the composition system is 8 to 10, the pH value of the system is not in the range of 8 to 10. The composition has a longer sterilization and disinfection time than the composition within the range.

Another object of the present invention is to provide a pharmaceutical composition for environmental disinfection.

For realizing the above-mentioned purpose of the invention, the technical scheme adopted in the present invention is:

A pharmaceutical composition for environmental disinfection, characterized in that each 1L of the composition includes 30-200 g of single-chain quaternary ammonium salt, 50-300 g of double-chain quaternary ammonium salt, 0.005-0.5 g of solution stabilizer, acid-base Conditioner 0.5～3g, the rest is purified water.

Wherein, the single-chain quaternary ammonium salt is selected from: dodecyldimethylbenzyl ammonium bromide, dodecyldimethylbenzyl ammonium chloride, tetradecyldimethylbenzyl chloride Ammonium, Cetyl Dimethyl Ethyl Ammonium Bromide, Cetyl Dimethyl Benzyl Ammonium Bromide, Cetyl Dimethyl Benzyl Ammonium Chloride, Cetyl Dimethyl Ammonium Chloride, Poridium Chloride , one or more compositions of benzethonium chloride; wherein, the dodecyl dimethyl benzyl ammonium chloride is selected from: dodecyl (60% C ₁₄ , 30% C ₁₆ , 5% C ₁₈ , 5% C ₁₂ ) dimethylbenzyl ammonium chloride, dodecyl (50% C ₁₂ , 30% C ₁₄ , 17% C ₁₇ , 3% C ₁₈ ) dimethyl benzyl ammonium chloride, dodecyl (100% C ₁₄ ) dimethylbenzyl ammonium chloride, dodecyl (50% C ₁₄ , 40% C ₁₂ , 10% C ₁₆ ) dimethylbenzyl chloride One of ammonium chloride and dodecyl (58% C ₁₄ , 28% C ₁₆ , 14% C ₁₂ ) dimethylbenzyl ammonium chloride.

Wherein, the described double-chain quaternary ammonium salt is selected from: dioctyl dimethyl ammonium chloride, octyl decyl dimethyl ammonium chloride, bis-decyl dimethyl ammonium chloride, didecyl/dioctyl ammonium chloride A combination of one or more of the group consisting of bis-octyl dimethyl ammonium chloride, bis-octyl dimethyl ammonium chloride and bis-decyl dimethyl ammonium bromide.

Wherein, the solution stabilizer is selected from: polyphosphate, 1,3-diketone, hydroxycarboxylic acid, disodium EDTA, polyamine, aminocarboxylic acid, Provichem 2202, Provichem 2203, HT-944 , polyvinyl alcohol in one or two or more compositions. Preferably, the solution stabilizer is selected from: the composition of disodium EDTA and Provichem 2203; the weight ratio between the disodium EDTA and Provichem 2203 is 1:1 to 10:1 , the most preferred solution stabilizer is selected from: the composition of disodium EDTA and Provichem 2203; the weight ratio of disodium EDTA and the composition of Provichem 2203 is 3:1.

Wherein, the pH value of the composition is 8-10.

Most preferably, the composition of the present invention includes 100 g dodecyl (50% C ₁₄ , 40% C ₁₂ , 10% C ₁₆ ) dimethylbenzyl ammonium chloride, 150 g bisdecyl dichloride per 1 L Methyl ammonium chloride, 0.06g disodium EDTA, 0.02g Provichem2203, appropriate amount of acid-base regulator to pH 8-10, and the rest are purified water.

The preparation method of the composition of the present invention comprises the following steps:

1) Mix the single-chain quaternary ammonium salt bulk drug with an appropriate amount of purified water, and heat it at 70°C to completely melt it into a flowable state;

2) Add the double-chain quaternary ammonium salt and the solution stabilizer successively and stir evenly on the stirrer;

3) The pH value of the pharmaceutical composition for environmental disinfection is adjusted to 8-10 with an acid-base regulator, and the volume is constant.

Preferably, the preparation method of the composition of the present invention includes the following steps: mixing the single-chain quaternary ammonium salt bulk drug with an appropriate amount of purified water, heating at 70° C. to make it completely melted into a flowable state; sequentially adding the double-chain quaternary ammonium salt, The solution stabilizer is stirred evenly on the stirrer; the pH value of the pharmaceutical composition for environmental disinfection is adjusted to 8-10 with an acid-base regulator, and the volume is determined.

The main components of the pharmaceutical composition for environmental disinfection prepared by the invention are dodecyl (50% C ₁₄ , 40% C ₁₂ , 10% C ₁₆ ) dimethylbenzyl ammonium chloride and bisdecyl dimethyl ammonium chloride. Dodecyl (50% C ₁₄ , 40% C ₁₂ , 10% C ₁₆ ) dimethylbenzyl ammonium chloride is a single chain quaternary ammonium salt, and bisdecyl dimethyl ammonium chloride is a double chain quaternary ammonium salt . The microbial killing effect of quaternary ammonium salts originates from the interaction between the cationic head group of quaternary ammonium nitrogen in its molecule and the negatively charged head group of acidic phospholipids in the cell membrane. Once the two are combined, the hydrophobic tail group of quaternary ammonium salts At higher quaternary ammonium salt concentrations, the cell membrane will form mixed micellar aggregates with quaternary ammonium salts and be disintegrated. Quaternary ammonium salt disinfectants have bacteriostatic effect at low concentrations, and can kill most types of bacterial propagules and some viruses at higher concentrations.

The pharmaceutical composition for environmental disinfection prepared by the invention has simple preparation process, good disinfection effect, high stability, long sterilization and disinfection time, low cost, is suitable for large-scale industrial production, and has great significance for the sustainable development of animal husbandry. .

The pharmaceutical composition for environmental disinfection prepared by the present invention is a better pharmaceutical composition for environmental disinfection than conventional pharmaceutical compositions for environmental disinfection. The composition uses a combination of disodium EDTA and Provichem 2203. Compared with a pharmaceutical composition for environmental disinfection obtained by other inventions, the composition has higher stability and better sterilization and disinfection effect. And select the composition of disodium EDTA and Provichem 2203 as a solution stabilizer to obtain a pharmaceutical composition for environmental disinfection, when the pH value of the composition system is 8 to 10, the pH value of the system is not in the range of 8 to 10. The composition has a longer sterilization and disinfection time than the composition within the range.

At present, the existing quaternary ammonium salts on the market kill microorganisms: benzalkonium bromide solution, benzalkonium chloride solution, compound glutaraldehyde solution, wherein each composition and the type of the present invention are: benzalkonium chloride solution, Compound glutaraldehyde solution.

The components include: the main components of the benzalkonium chloride solution are benzalkonium chloride, and the main components of the compound glutaraldehyde solution are glutaraldehyde and benzalkonium chloride.

The disadvantage is: the benzalkonium chloride solution is a single-chain quaternary ammonium salt single preparation, and its disinfection range is narrow, only for specific bacteria; the compound glutaraldehyde solution is a compound preparation of glutaraldehyde and single-chain quaternary ammonium salt, and its disinfection range is narrow. The scope of disinfection is not as wide as that of single-chain quaternary ammonium salts and double-chain quaternary ammonium salts, and the preparation takes a long time to sterilize, generally more than 10 hours, and glutaraldehyde has certain toxicity, which can cause bronchitis and pulmonary edema.

The main difference between it and the present invention is that the known quaternary ammonium salts have a narrow range of killing bacteria and viruses, while the composition of the present invention is effective against RNA viruses, parvoviruses, adenoviruses, and polioviruses. , bird flu, Newcastle disease, infectious bursal disease and other bacteria and viruses have obvious effects; the known quaternary ammonium salts have a short sterilization time for killing microorganisms, and a long sterilization onset time, and the composition of the present invention sterilizes The effect is more durable, and the killing rate of various bacteria and viruses can reach more than 99.9% in about 2.5 minutes.

The currently reported products containing the same components as the present invention include: veterinary disinfectant and preparation method thereof (application number: 200910087914.5, the components similar to the present invention include benzalkonium chloride and didecyldimethylammonium bromide), A novel disinfectant prepared by utilizing quaternary ammonium salt and alcohol (application number: 201410807324.6, and the components similar to the present invention include benzalkonium chloride, benzalkonium bromide, cetyltrimethylammonium, bisdecyldimethylammonium At least one of base ammonium, alkyl trimethyl ammonium carbonate), quaternary ammonium salt polymer and copolymer disinfectant (application number: 200680039366.3, similar components to the present invention include benzalkonium chloride, benzethonium chloride , dimethyl didecyl ammonium chloride or their mixture), disinfectant that can be used in high multiple dilution, preparation method and use (application number: 201010216594.1, similar components to the present invention include dimethyl didecyl Ammonium chloride, benzalkonium bromide, benzalkonium chloride, dodecyldimethylethoxyethylammonium bromide, dimethyl bisdecyl ammonium chloride, dimethyl bisdecyl ammonium bromide, One or more mixtures of dimethyl bisdecyl ammonium carbonate, dimethyl bistetradecyl ammonium chloride, dimethyl bishexadecyl ammonium chloride, benzethonium chloride), food Field disinfectant and preparation method (application number: 201010219496.3, the components similar to the present invention include benzalkonium bromide, benzalkonium chloride, dimethyldidodecylammonium chloride, dimethyldihexadecyl chloride Ammonium bromide, Dodecyldimethylethoxyethylammonium bromide, Dimethylbisdecylammonium chloride, Dimethylbisdecylammonium bromide, Dimethylbisdecylammonium carbonate, Dimethyl bisdecylammonium bromide One or more of ditetradecyl ammonium chloride and benzethonium chloride) and topical antimicrobial composition (application number: 201780025348.8, the components similar to the present invention include didecyl dimethyl chloride ammonium, benzethonium chloride, benzalkonium chloride, polydiallyldimethylammonium chloride or mixtures thereof).

Veterinary disinfectant and its preparation method (application number: 200910087914.5) only announced the average bactericidal rate of Escherichia coli and Staphylococcus aureus within 10min of different multiple dilutions; a new type of disinfectant prepared by utilizing quaternary ammonium salt and alcohol (application No.: 201410807324.6) only published the average bactericidal rate within 5min of Escherichia coli 8099, Staphylococcus aureus ATCC6538, Candida albicans ATCC10231, Pseudomonas aeruginosa ATCC15442 and Aspergillus niger; disinfectants of quaternary ammonium salt polymers and copolymers ( Application No.: 200680039366.3) only published the average bacteriostatic ability against Escherichia coli, Staphylococcus aureus, MSRA, and vancomycin-resistant Enterococcus faecalis within 48 hours; disinfectants that can be used in high multiple dilution, preparation methods and uses (application No. : 201010216594.1) only published the average sterilization rate of Escherichia coli, Candida albicans and Staphylococcus aureus within 20min with different dilutions; Disinfectants and preparation methods in the food field (application number: 201010219496.3) only published the effects of different dilutions on Escherichia coli The average bactericidal effect within 10min; the topical antimicrobial composition (application number: 201780025348.8) only published the average bactericidal effect of different dilutions on Escherichia coli within 3h. The above-reported products containing the same ingredients as the present invention do not reflect its long-term sterilization rate effect.

The main advantage of the present invention compared with the currently reported products containing the same components as the present invention is that the present invention has a relatively obvious disinfection effect on various bacteria and viruses, and the onset time of sterilization and antivirus is short. Better sex and longer lasting disinfection.

Below by experimental data comparison, illustrate that the technology of the present invention is superior to the product technology related to the present invention disclosed at present:

The present invention and the above-mentioned two kinds of disinfectants and the product related to the present invention are diluted into a certain concentration with sterilized hard water according to the instructions for use, and the test grouping is set to see the following table 1, and the test result table 2 and table 3:

Table 1 Test grouping and dilution ratio

Remarks: D1 product is a product prepared according to veterinary disinfectant and its preparation method (application number: 200910087914.5);

D2 product is the product prepared according to a kind of novel disinfectant (application number: 201410807324.6) prepared by utilizing quaternary ammonium salt and alcohol;

D3 product is a product prepared according to the disinfectant of quaternary ammonium salt polymer and copolymer (application number: 200680039366.3);

D4 product is a product prepared according to the disinfectant, preparation method and use that can be used in high multiple dilution (application number: 201010216594.1);

D5 product is a product prepared according to the disinfectant in the food field and its preparation method (application number: 201010219496.3);

D6 product is a product prepared according to the topical antimicrobial composition (application number: 201780025348.8);

Table 2 compares the disinfection effect of Escherichia coli

Note: The above results are the average of 3 experiments.

Table 3 compares the disinfection effect of Staphylococcus aureus

Note: The above results are the average of 3 experiments.

The test results show that the invention has good killing effects on Escherichia coli and Staphylococcus aureus, and the killing rate on Escherichia coli and Staphylococcus aureus has reached more than 99.7% at 2.5min, and it kills at 120h. The rate is still 99.8%. The killing effect of benzalkonium chloride solution and compound glutaraldehyde solution on Escherichia coli and Staphylococcus aureus is relatively poor, there is no killing effect at 2.5min, and the killing effect on Escherichia coli and Staphylococcus aureus at 60min The effect was the highest, and the killing effect decreased significantly with the increase of time. The killing effect of D1-D6 products on Escherichia coli and Staphylococcus aureus is obviously lower than that of the present invention, and with the increase of time, the killing effect has a downward trend, and is obviously lower than the killing effect of the present invention.

The formula of the present invention is obtained through screening, and the screening process is as follows:

1 Active ingredient screening

1.1 Recipe screening

The minimum inhibitory and bactericidal concentrations of various single- and double-chain quaternary ammonium salts were determined by Escherichia coli 8099 and Staphylococcus aureus ATCC6538, and the single- and double-chain quaternary ammonium salts with the best bactericidal effect were screened. The specific screening results are shown in Table 4-1.

Table 4-1 Determination results of minimum inhibitory and bactericidal concentrations (MIC/MBC) of quaternary ammonium salt disinfectants

Note: The above results are the average of 3 experiments. The experimental conditions were 20±1℃, and the action time of MBC group was 5min.

The negative control group grew aseptically.

The results showed that the minimum inhibitory concentration of benzalkonium chloride for Escherichia coli was 0.004μg/ml, and the minimum bactericidal concentration was 0.061μg/ml. The bacteriostatic and bactericidal effects were the best. The minimum inhibitory concentration of Staphylococcus aureus is 0.001μg/ml, and the minimum bactericidal concentration is 0.015μg/ml, and the bacteriostatic and bactericidal effects are the best; the double-chain quaternary ammonium salt of decamethonium chloride has the minimum inhibitory concentration on Escherichia coli The minimum bactericidal concentration is 0.004μg/ml, the minimum bactericidal concentration is 0.030μg/ml, and the antibacterial and bactericidal effects are the best. /ml, the antibacterial and bactericidal effects are the best. Therefore decided to select benzalkonium chloride, decyl ammonium chloride as the compound ingredients of the present invention.

1.2 Proportional screening

The veterinary disinfectant indicator bacteria Escherichia coli 8099 and Staphylococcus aureus ATCC6538 were used as test strains to carry out the combined drug susceptibility test. Using the checkerboard method, using a 96-well sterile microplate, according to the measured MIC values of single- and double-chain quaternary ammonium salts, 9 times MIC, 3 times MIC, 1 times MIC, 1/3 MIC, 1/9 MIC of the two drugs were used respectively. Make a union. The checkerboard test was repeated 3 times for each strain. The test results were based on the partial inhibitory concentration (FIC) index as the judgment basis for the combined drug susceptibility test.

Result judgment: According to the antibacterial situation of the combined drug susceptibility and the single drug susceptibility, the partial inhibitory concentration index (FIC) was used as the judgment basis.

Note: When FIC≤0.5, it means synergy;

When 0.5<FIC≤1, it means additive effect;

When 1<FIC≤2, it means irrelevant effect;

When FIC>2, antagonism is indicated.

Table 4-2 Results of the combined drug susceptibility test of benzalkonium chloride and decamethylammonium chloride to Escherichia coli (8099)

Note: The above results are the average of 3 experiments. The test conditions are all 20±1℃. The positive control group was cloudy, and the negative control group grew sterile.

Benzalkonium chloride-decamethonium chloride (1:2): FIC=0.0004/0.004+0.001/0.004=0.35, synergistic effect

Benzalkonium chloride-decamethonium chloride (1:1): FIC=0.001/0.004+0.001/0.004=0.5, synergistic effect

Benzalkonium chloride-decamethonium chloride (2:1): FIC=0.001/0.004+0.0004/0.004=0.35, synergistic effect

Table 4-3 The results of the combined drug susceptibility test of benzalkonium chloride and decamethonium chloride against Staphylococcus aureus (ATCC 6538)

Note: The above results are the average of 3 experiments. The test conditions are all 20±1℃. The positive control group was cloudy, and the negative control group grew sterile.

Benzalkonium chloride-decamethonium chloride (1:2): FIC=0.0004/0.004+0.001/0.004=0.35, synergistic effect

Benzalkonium chloride-decamethonium chloride (1:1): FIC=0.001/0.004+0.001/0.004=0.5, synergistic effect

Benzalkonium chloride-decamethonium chloride (2:1): FIC=0.001/0.004+0.0004/0.004=0.35, synergistic effect

The results showed that: by MIC/MBC screening of a single quaternary ammonium salt drug, benzalkonium chloride and decamethylammonium chloride with the best antibacterial and bactericidal effects were screened out as the main ingredients of the formula. Through the combined drug susceptibility test of the disinfectant indicator bacteria Escherichia coli 8099 and Staphylococcus aureus ATCC6538, it was found that when the ratio of benzalkonium chloride and decamethonium chloride was between 2:1-1:2, the two drugs showed a synergistic effect , the bacteriostatic effect is the strongest, comprehensive consideration, it is determined that the ratio of benzalkonium chloride of the present invention and decamethylammonium chloride is 1:1.5.

2 Selection of stabilizer types and concentrations

Quaternary ammonium salt disinfectants are all cationic surfactants, so they cannot be used in combination with anionic surfactants, such as soap, lecithin, washing powder, Tween-80, and some other substances have antagonistic effects with quaternary ammonium salt disinfectants. , For example, iodine, potassium iodide, protein silver, salicylic acid, mercuric chloride, peroxide, calcium, magnesium, iron, aluminum and other metal ions have antagonistic effects.

Source of stabilizer:

EDTA·2Na: purchased from Nanjing Chemical Reagent Co., Ltd., analytically pure;

Polyvinyl alcohol: purchased from Jiangxi Alpha Hi-Tech Pharmaceutical Co., Ltd., analytically pure;

Provichem 2203: purchased from Provien Company, pharmaceutical grade, is a new type of copolymerization stabilizer, and has not been reported to be used in the field of disinfection;

2.1 Screening of different types of stabilizer concentrations

Establishment of test conditions: Three commonly used stabilizers, EDTA·2Na, polyvinyl alcohol, and Provichem 2203, were selected, and different concentrations were set to prepare prescription preparations. The optimal type and concentration of stabilizer were screened out. The specific screening results are shown in Tables 4-4 to 4-6.

Table 4-4 Characterization of EDTA·2Na as Stabilizer

Table 4-5 Characterization of polyvinyl alcohol as stabilizer

Table 4-6 Characterization of Provichem 2203 as stabilizer

表示，用字母标记法标示，出现P＜0.05 表示差异显著；P＞0.05表示差异不显著，以期选出最佳的稳定剂种类和浓度。The above test results show that different kinds of stabilizers have no obvious effect on the properties, pH value, clarity and main drug component content of the present invention. The diameter of the inhibition zone of Staphylococcus aureus, Escherichia coli and Candida albicans, the test data were collected by Excel, and SPSS 17.0 software was used for variance analysis.

It is indicated by letter notation, P<0.05 means significant difference; P>0.05 means no significant difference, in order to select the best stabilizer type and concentration.

We first analyzed the optimal concentration data of EDTA·2Na, polyvinyl alcohol, and Provichem 2203, respectively. The specific results are shown in Tables 4-7 to 4-9.

The bacteriostatic effect of table 4-7 different concentrations of EDTA·2Na on Staphylococcus aureus, Escherichia coli and Candida albicans

Note: Different lowercase letters in the same column indicate significant difference, P < 0.05; no mark or the same letter indicates no significant difference, P > 0.05.

It can be seen from the above results that:

Staphylococcus aureus: In the investigated EDTA·2Na concentration, when the added concentration is 0.006%, the present invention has better bacteriostatic effect on Staphylococcus aureus, and is significantly better than the bacteriostatic effect of other concentrations. Therefore, 0.006% EDTA·2Na was chosen to be added to the present invention.

Escherichia coli: In the investigated EDTA·2Na concentration, when the added concentration is 0.006%, the present invention has better bacteriostatic effect on Escherichia coli, and is significantly better than the bacteriostatic effect of other concentrations. Therefore, 0.006% EDTA·2Na was chosen to be added to the present invention.

Candida albicans: in the investigated EDTA·2Na concentration, when the added concentration is 0.002%, the present invention has better bacteriostatic effect on Candida albicans, and is significantly better than the bacteriostatic effect of other concentrations. When the added concentration is 0.006%, its bacteriostatic effect on Candida albicans is second only to that of the present invention with a concentration of 0.002%, and is significantly better than the bacteriostatic effect of other concentrations.

The main function of the disinfectant is to target a variety of bacteria, rather than simply targeting a certain pathogen. Therefore, in view of the above, it is tentatively chosen to add 0.006% EDTA·2Na to the present invention.

Table 4-8 The antibacterial effect of different concentrations of polyvinyl alcohol on Staphylococcus aureus, Escherichia coli and Candida albicans

Note: Different lowercase letters in the same column indicate significant difference, P < 0.05; no mark or the same letter indicates no significant difference, P > 0.05.

It can be seen from the above results that:

Staphylococcus aureus: In the investigated concentration of polyvinyl alcohol, when the added concentration is 0.001%, the present invention has better bacteriostatic effect on Staphylococcus aureus, and is significantly better than the bacteriostatic effect of other concentrations. Therefore, 0.001% polyvinyl alcohol was chosen to be added to the present invention.

Escherichia coli: Among the polyvinyl alcohol concentrations investigated, when the added concentrations are 0.001% and 0.002%, the present invention has better bacteriostatic effect on Escherichia coli, and is significantly better than other concentrations. Therefore, 0.001% or 0.002% polyvinyl alcohol can be added to the present invention.

Candida albicans: In the investigated concentration of polyvinyl alcohol, when the added concentrations are 0.001%, 0.002%, 0.005% and 0.010%, the antibacterial effect of the present invention on Candida albicans is equivalent, and significantly better than the concentration of 0.020 % and the bacteriostatic effect of no added polyvinyl alcohol.

To sum up, 0.001% of polyvinyl alcohol can be temporarily added to the present invention to make the antibacterial effect of the present invention reach a better level.

Table 4-9 The antibacterial effect of different concentrations of Provichem 2203 on Staphylococcus aureus, Escherichia coli and Candida albicans

Note: Different lowercase letters in the same column indicate significant difference, P < 0.05; no mark or the same letter indicates no significant difference, P > 0.05.

It can be seen from the above results that:

Staphylococcus aureus: Among the investigated concentrations of Provichem 2203, when the added concentrations are 0.005% and 0.002%, the present invention has better bacteriostatic effect on Staphylococcus aureus, and is significantly better than other concentrations. Therefore, 0.005% and 0.002% of Provichem 2203 may optionally be added to the present invention.

Escherichia coli: Among the investigated concentrations of Provichem 2203, when the added concentrations are 0.005% and 0.002%, the present invention has better bacteriostatic effect on Escherichia coli, and is significantly better than other concentrations. Therefore, 0.005% and 0.002% of Provichem 2203 can be added to the present invention.

Candida albicans: Among the investigated concentrations of Provichem 2203, when the added concentration is 0.002%, the present invention has better bacteriostatic effect on Candida albicans, and is significantly better than the bacteriostatic effect of other concentrations. Therefore, 0.005% of Provichem 2203 can be added to the present invention.

To sum up, 0.002% of Provichem 2203 can be added to the present invention to make the antibacterial effect of the present invention reach a better level.

2.2 Screening of stabilizer types

Compare the bacteriostatic effects of EDTA·2Na, polyvinyl alcohol, and Provichem 2203 of the above-selected optimal concentrations on Staphylococcus aureus, Escherichia coli, and Candida albicans, in order to screen out the optimal stabilizer. type.

Table 4-10 The antibacterial effect of different proportions of stabilizers on Staphylococcus aureus, Escherichia coli and Candida albicans

Note: Different lowercase letters in the same column indicate significant difference, P < 0.05; no mark or the same letter indicates no significant difference, P > 0.05.

It can be seen from the above results that EDTA·2Na:Provichem 2203=3:1 has good bacteriostatic effect on Staphylococcus aureus, Escherichia coli and Candida albicans, and is significantly better than other combinations of stabilizers. Therefore, EDTA·2Na:Provichem 2203=3:1 was selected as the optimum stabilizer type and concentration in the present invention, that is, the concentration of EDTA·2Na was 0.006%, and the concentration of Provichem 2203 was 0.002%.

3 The choice of pH

Establishment of test conditions: 5 preparation samples were prepared according to the prescription of the present invention, and the pH was adjusted to 2, 4, 6, 8, and 10 with sodium hydroxide or hydrochloric acid test solution, respectively. The properties, clarity, precipitation and bacteriostatic effect of each pH value preparation were investigated in order to screen out the best pH value.

Table 4-11 Investigation on the properties of the present invention with different pH values

表示，用字母标记法标示， 出现P＜0.05表示差异显著；P＞0.05表示差异不显著，以期选出最佳的pH值。具体结果 见表4-12。Take 5 parts of 50ml of the complete test sample packaged under each pH condition, adopt the drug sensitive tablet method, and measure the diameter of the inhibition zone of Staphylococcus aureus, Escherichia coli and Candida albicans of the present invention with different pH values, The experimental data were collected using Excel, and SPSS17.0 software was used for variance analysis.

Indicated by letter notation, P<0.05 means significant difference; P>0.05 means no significant difference, in order to select the best pH value. The specific results are shown in Table 4-12.

Table 4-12 Bacteriostatic effect of different pH values on Staphylococcus aureus, Escherichia coli and Candida albicans

Note: Different lowercase letters in the same column indicate significant difference, P < 0.05; no mark or the same letter indicates no significant difference, P > 0.05.

It can be seen from the above results that:

Staphylococcus aureus: Among the pH values investigated, the bacteriostatic effects of pH 8 and 10 groups were the best, and were significantly higher than those of pH 2, 4, and 6 groups. Therefore, when the pH value is 8-10, the present invention has better bacteriostatic effect on Staphylococcus aureus.

Escherichia coli: Among the pH values investigated, pH 8 group had the best bacteriostatic effect, followed by pH 10 group, which was significantly higher than pH 2, 4, and 6 groups. Therefore, when the pH value is 8-10, the antibacterial effect of the present invention on Escherichia coli is better.

Candida albicans: Among the pH values investigated, pH 8 group had the best bacteriostatic effect, followed by pH 10 group, which was significantly higher than pH 2, 4, and 6 groups. Therefore, when the pH value is 8-10, the antibacterial effect of the present invention on Candida albicans is better.

To sum up, considering that the function of the present invention is mainly used to kill microorganisms such as bacteria and fungi, the pH value of the present invention is set at 8-10, and the pH value is most preferably 8.

Detailed ways

Example 1

Mix 30 g of dodecyl (50% C ₁₄ , 40% C ₁₂ , 10% C ₁₆ ) dimethylbenzyl ammonium chloride bulk drug with an appropriate amount of purified water, and heat it at 70°C to melt it completely into a flowable state ; Add 60g bis-decyl dimethyl ammonium chloride successively, 0.006g disodium EDTA, 0.002g Provichem 2203 and stir on the stirrer; Adjust the pH of the pharmaceutical composition for environmental disinfection with an acid-base regulator The value is 8-10, and the purified water is adjusted to 1L to obtain a pharmaceutical composition for environmental disinfection.

Embodiment 2

Mix 50 g of dodecyl (50% C ₁₄ , 40% C ₁₂ , 10% C ₁₆ ) dimethylbenzyl ammonium chloride bulk drug with an appropriate amount of purified water, and heat it at 70°C to melt it completely into a flowable state ; Add 75g of bis-decyl dimethyl ammonium chloride, 0.015g of disodium EDTA, 0.008g of Provichem 2203 and stir on the stirrer successively; Adjust the pH of the pharmaceutical composition for environmental disinfection with an acid-base regulator The value is 8-10, and the purified water is adjusted to 1L to obtain a pharmaceutical composition for environmental disinfection.

Embodiment 3

Mix 100 g of dodecyl (50% C ₁₄ , 40% C ₁₂ , 10% C ₁₆ ) dimethylbenzyl ammonium chloride raw material drug with an appropriate amount of purified water, and heat at 70°C to completely melt it into a flowable state ; Add 150g of bisdecyl dimethyl ammonium chloride successively, 0.06g of disodium EDTA, 0.02g of Provichem 2203 and stir on the stirrer; Adjust the pH of the pharmaceutical composition for environmental disinfection with an acid-base regulator The value is 8-10, and the purified water is adjusted to 1L to obtain a pharmaceutical composition for environmental disinfection.

Embodiment 4

Mix 100 g of dodecyl (50% C ₁₄ , 40% C ₁₂ , 10% C ₁₆ ) dimethylbenzyl ammonium chloride raw material drug with an appropriate amount of purified water, and heat at 70°C to completely melt it into a flowable state ; Add 200g bisdecyl dimethyl ammonium chloride successively, 0.3g disodium EDTA, 0.2g Provichem 2203 and stir on the stirrer; Adjust the pH of the pharmaceutical composition for environmental disinfection with an acid-base regulator The value is 8-10, and the purified water is adjusted to 1L to obtain a pharmaceutical composition for environmental disinfection.

Embodiment 5

Mix 150 g of dodecyl (50% C ₁₄ , 40% C ₁₂ , 10% C ₁₆ ) dimethylbenzyl ammonium chloride raw material drug with an appropriate amount of purified water, and heat at 70°C to completely melt into a flowable state ; Add 200g of bisdecyl dimethyl ammonium chloride successively, 0.2g of disodium EDTA, 0.08g of Provichem 2203 and stir on the stirrer; Adjust the pH of the pharmaceutical composition for environmental disinfection with an acid-base regulator The value is 8-10, and the purified water is adjusted to 1L to obtain a pharmaceutical composition for environmental disinfection.

Embodiment 6

Mix 200 g of dodecyl (50% C ₁₄ , 40% C ₁₂ , 10% C ₁₆ ) dimethylbenzyl ammonium chloride raw material with an appropriate amount of purified water, and heat it at 70°C to completely melt it into a flowable state ; Add 250g of bis-decyl dimethyl ammonium chloride, 0.006g of disodium EDTA, 0.004g of Provichem 2203 and stir on the stirrer successively; Adjust the pH of the pharmaceutical composition for environmental disinfection with an acid-base regulator The value is 8-10, and the purified water is adjusted to 1L to obtain a pharmaceutical composition for environmental disinfection.

Embodiment 7

Mix 200 g of dodecyl (50% C ₁₄ , 40% C ₁₂ , 10% C ₁₆ ) dimethylbenzyl ammonium chloride raw material with an appropriate amount of purified water, and heat it at 70°C to completely melt it into a flowable state ; Add 300g of bisdecyl dimethyl ammonium chloride successively, 0.15g of disodium EDTA, 0.1g of Provichem 2203 and stir on the stirrer; Adjust the pH of the pharmaceutical composition for environmental disinfection with an acid-base regulator The value is 8-10, and the purified water is adjusted to 1L to obtain a pharmaceutical composition for environmental disinfection.

The dosage of each component described in one of Examples 1 to 7 is increased or decreased according to the same proportion, and the relationship between the weight and the fraction of each component obtained belongs to the protection scope of the present invention.

Embodiment 8

Stability test

The test sample is a pharmaceutical composition for environmental disinfection prepared in Example 1, Example 2, and Example 3; the test items include properties, pH value, clarity, microbial killing effect, and content.

accelerated test

The three batches of samples prepared in Example 1, Example 2, and Example 3 were placed under the conditions of 40±2°C and 65±5% relative humidity for six months, and samples were taken at the end of the 0th, 1st, 2nd, 3rd, and 6th months. , investigate the properties, pH value, clarity, microbial killing effect, content and other items, and compare with the test results of 0 days. The results are shown in Table 1 below.

long term trial

The three batches of samples prepared in Example 1, Example 2 and Example 3 were placed under the conditions of 25±2°C and relative humidity of 60±10%. Sampling was carried out to investigate the properties, pH value, clarity, microbial killing effect, content and other items, and compared with the test results of 0 days, the results are shown in Table 2 below.

Table 1 Accelerated test results of three batches of samples

Note: a represents the sterilization rate;

b represents dodecyl (50% C ₁₄ , 40% C ₁₂ , 10% C ₁₆ ) dimethylbenzylammonium chloride;

c stands for bisdecyldimethylammonium chloride

Table 2 Long-term test results of three batches of samples

Note: a represents the sterilization rate;

b represents dodecyl (50% C ₁₄ , 40% C ₁₂ , 10% C ₁₆ ) dimethylbenzylammonium chloride;

c stands for bisdecyldimethylammonium chloride

It can be seen from the accelerated test and long-term test results that the three batches of samples prepared by Example 1, Example 2 and Example 3 were placed under the conditions of 40±2°C, RH65±5% for 6 months and at 25±2°C, After being placed for 36 months under the condition of RH60±10%, the appearance of the sample has no obvious change, the pH and clarity are in compliance with the regulations, the content change is not significant, and the killing effect of microorganisms has no significant change, indicating that the invention made an environment. The medicinal composition for disinfection has high quality stability, stable sterilization rate and long sterilization and disinfection time.

The combination obtained by increasing or decreasing the dosage of each component described in one of the first to seventh embodiments and one of the first to seventh embodiments, the stability test and the results are all within the protection scope of the present invention.

Claims (8)

1. The pharmaceutical composition for environmental disinfection is characterized in that each 1L of the pharmaceutical composition comprises 30-200 g of single-chain quaternary ammonium salt, 50-300 g of double-chain quaternary ammonium salt, 0.005-0.5 g of solution stabilizer, 0.5-3 g of acid-base regulator and the balance of purified water.

2. The composition of claim 1, wherein said single chain quaternary ammonium salt is selected from the group consisting of: one or more of dodecyl dimethyl benzyl ammonium bromide, dodecyl dimethyl benzyl ammonium chloride, tetradecyl dimethyl benzyl ammonium chloride, hexadecyl dimethyl ethyl ammonium bromide, hexadecyl dimethyl benzyl ammonium chloride, miropyram, polonium chloride and benzethonium chloride; wherein, the dodecyl dimethyl benzyl ammonium chloride is selected from: dodecyl (60% C)₁₄，30％C₁₆，5％C₁₈，5％C₁₂) Dimethyl benzyl ammonium chloride, dodecyl (50% C)₁₂，30％C₁₄，17％C₁₇，3％C₁₈) Dimethyl benzyl ammonium chloride, dodecyl (100% C)₁₄) Dimethyl benzyl ammonium chloride, dodecyl (50% C)₁₄，40％C₁₂，10％C₁₆) Dimethyl benzyl ammonium chloride, dodecyl (58% C)₁₄，28％C₁₆，14％C₁₂) One kind of dimethyl benzyl ammonium chloride.

3. The composition of claim 1, wherein said double-stranded quaternary ammonium salt is selected from the group consisting of: one or more of dioctyl dimethyl ammonium chloride, octyl decyl dimethyl ammonium chloride, didecyl/dioctyl dimethyl ammonium chloride, dioctyl dimethyl ammonium chloride and didecyl dimethyl ammonium bromide.

4. The composition of claim 1, wherein the solution stabilizer is selected from the group consisting of: one or more of polyphosphate, 1, 3-diketone, hydroxycarboxylic acid, disodium ethylene diamine tetraacetate, polyamine, aminocarboxylic acid, Provichem 2202, Provichem2203, HT-944 and polyvinyl alcohol.

5. The composition of claim 1, wherein the solution stabilizer is selected from the group consisting of: a combination of disodium edetate and Provichem 2203; the weight ratio of the disodium ethylene diamine tetraacetate to the Provichem2203 is 1: 1-10: 1.

6. The composition of claim 1, wherein the solution stabilizer is selected from the group consisting of: a combination of disodium edetate and Provichem 2203; the weight ratio of the disodium ethylene diamine tetraacetate to the Provichem2203 composition is 3: 1.

7. The composition of claim 1, wherein the composition has a pH of 8 to 10.

8. The composition of claim 1, comprising 100g dodecyl (50% C) per 1L₁₄，40％C₁₂，10％C₁₆) Dimethyl benzyl ammonium chloride, 150g of didecyl dimethyl ammonium chloride, 0.06g of ethylene diamine tetraacetic acid disodium, 0.02g of Provichem2203, a proper amount of an acid-base regulator until the pH value is 8-10, and the balance of purified water.