CN111328811A - Low-concentration alcohol sterilization disinfectant and application thereof - Google Patents

Abstract

The invention discloses a low-concentration alcohol sterilizing and disinfecting liquid and its application. The bactericidal disinfectant contains 0.01-1% of chloroquine or a chloroquine derivative and 10-30% of ethanol. The bactericidal disinfectant is used in combination with low-concentration alcohol and chloroquine phosphate, and has obvious synergistic effect, which can significantly increase the bacteriostatic rate to 100% at a lower concentration of chloroquine phosphate, and the ethanol concentration is low, with a broad spectrum , efficient and safe disinfection and sterilization activity, and can be further developed into antibacterial and disinfection products of various dosage forms, so it has the potential to be used as a commonly used, safe and efficient bactericidal disinfectant, and has a good application prospect. .

Description

A kind of low-concentration alcohol sterilizing and disinfecting liquid and its application

technical field

The invention relates to the technical field of disinfection and protection. More specifically, it relates to a low-concentration alcohol sterilizing disinfectant and its application.

Background technique

The outbreak of novel coronavirus (2019-nCoV) pneumonia since December 2019 has made people pay more attention to daily antibacterial disinfection. In the research on SARS-related coronaviruses, it was found that chloroquine can effectively prevent the spread of SARS-related coronaviruses in the process of cell culture, and the mechanism of action is to inhibit the terminal glycosylation of ACE2. And existing clinical studies have found that chloroquine phosphate has initially shown good clinical efficacy on the new coronavirus, and it has been written into the "New Coronary Virus Pneumonia Diagnosis and Treatment Program (Trial Version 6)". Chloroquine phosphate is an antimalarial drug that has been used clinically for more than 70 years. Previous studies have clearly indicated that it not only has antimalarial effects, but also has broad-spectrum antiviral effects. However, there is no research and report on chloroquine-based external disinfection and bacteriostatic related cleaning products for the daily needs of antibacterial and antibacterial disinfection for external washing and nursing.

In addition, among the many existing disinfection products, alcohol, as the most commonly used disinfectant, is widely used in daily life, especially in the medical industry. The reason why alcohol can be disinfected is that it can absorb the moisture of bacterial protein, dehydrate, denature and solidify, so as to achieve the purpose of killing bacteria. At the same time, the strength of alcohol sterilization and disinfection ability is directly related to its concentration. Too high or too low will not work. If high concentration of alcohol is used, the dehydration of bacterial proteins is too rapid, so that the surface proteins of bacteria are first denatured and solidified, forming a layer of With a strong envelope, alcohol cannot penetrate into the bacteria well, which affects its bactericidal ability; therefore, 70% to 75% alcohol is usually used in the medical field, which can not only solidify the proteins that make up bacteria, but also cannot form an envelope. , which can make the alcohol continue to penetrate into the interior, and make it completely sterilized and disinfected. Among them, 75% of the alcohol has the strongest sterilization power, which is similar to the osmotic pressure of bacteria, and can gradually and continuously penetrate into the interior of the bacteria before the surface protein of the bacteria is not denatured. , to dehydrate, denature and solidify all bacterial proteins, and finally kill bacteria. For example, 75% alcohol can kill Escherichia coli, Staphylococcus aureus, Candida albicans, Pseudomonas aeruginosa, etc. in one minute at room temperature; while alcohol When the concentration is as low as about 30%, there is almost no bacteriostatic effect.

However, long-term use of high-concentration alcohol to disinfect the skin will have a certain irritating effect on the skin. And research conducted by Science Translational Medicine found that bacteria are becoming more tolerant to alcohol on the skin. The study found that Enterococcus faecium became more resistant to high concentrations of alcohol. Caused bacteria to survive longer after exposure to alcohol; in addition, studies also showed that vancomycin-resistant Enterococcus also began to adapt to alcohol, and the DNA of alcohol-resistant bacteria mutated at specific gene positions related to cellular metabolism Resistance to alcohol appears to have a complex genetic basis, like resistance to antibiotics. Therefore, there are potential risks in completely relying on higher concentrations of alcohol disinfectants. It is important to seek external disinfection and washing products with better antibacterial effect, safer and non-irritating effects for medical disinfection, daily disinfection and prevention and control of virus epidemics. Value.

SUMMARY OF THE INVENTION

The present invention aims to provide a disinfecting and washing care product for external use which is safe, non-irritating, and has remarkable bacteriostatic effect. The research of the present invention shows that chloroquine phosphate has obvious bactericidal and disinfecting effect in vitro and external use, and has a certain dose dependence, and using a lower concentration of chloroquine phosphate and compounding with a low concentration of alcohol (mass concentration below 30%), the bacteriostatic effect That is to say, it can be significantly improved. The combination of the two has an unexpected synergistic effect, and the antibacterial rate has been significantly increased to 100%. It has broad-spectrum, efficient and safe disinfection and sterilization activities, and can be further developed into various dosage forms. Therefore, it has the potential to be used as a common, safe and efficient sterilizing and disinfecting agent.

The primary purpose of the present invention is to provide a chloroquine-containing bactericidal disinfectant.

Another object of the present invention is to provide the application of the above-mentioned sterilizing and disinfecting liquid in the preparation of sterilizing and disinfecting products.

Another object of the present invention is to provide a sterilizing and disinfecting spray.

Another object of the present invention is to provide a sterilizing and disinfecting mouthwash.

In order to achieve the above object, the present invention is achieved through the following schemes:

The invention provides a bactericidal disinfectant, which comprises the following components in terms of mass volume percentage (w/v): 0.01-1% of chloroquine or a chloroquine derivative, 10-30% of ethanol, and the balance is water.

The bactericidal disinfectant of the present invention can significantly enhance the bacteriostatic and bactericidal effect of the low-concentration alcohol or chloroquine alone through the reasonable compounding of low-concentration alcohol and chloroquine. Stimulating, high safety performance, and can effectively reduce the probability of bacteria resistance to alcohol.

Preferably, by mass volume percentage, the sterilizing and disinfecting solution includes the following components: 0.01-0.8% of chloroquine or chloroquine derivatives, 10-20% of ethanol, and the balance is water.

Preferably, in terms of mass volume percentage, the sterilizing and disinfecting solution includes the following components: 0.01-0.5% of chloroquine or a chloroquine derivative, 10-20% of ethanol, and the balance is water.

Preferably, by mass volume percentage, the sterilizing and disinfecting solution includes the following components: 0.05-0.5% of chloroquine or chloroquine derivatives, 10-20% of ethanol, and the balance is water.

Preferably, in terms of mass volume percentage, the bactericidal disinfectant includes the following components: 0.05-0.1% of chloroquine or chloroquine derivatives, 10-20% of ethanol, and the balance is water.

More preferably, in terms of mass volume percentage, the sterilizing and disinfecting solution includes the following components: 0.1% of chloroquine or a chloroquine derivative, 20% of ethanol, and the balance is water.

Preferably, the chloroquine derivative is one or more of chloroquine phosphate, hydroxychloroquine, chloroquine sulfate, and chloroquine hydrochloride.

The present invention also claims to protect the application of the above-mentioned sterilizing and disinfecting liquid in the preparation of sterilizing and disinfecting products. The sterilization and disinfection products include various dosage forms of sterilizers, mouthwashes with sterilization and disinfection functions, hand sanitizers, and the like.

As an optional preferred solution, based on the above sterilizing and disinfecting liquid, the present invention also develops a sterilizing and disinfecting spray, which includes the following components in percentage by mass and volume: 10-30% of ethanol, chloroquine or chloroquine derivatives 0.01-1% of sterilizing agent, 9-12% of moisturizing and penetration enhancer, the balance being water and pH adjusting agent, and the pH of the disinfecting spray is 4-7.

The above sterilization and disinfection spray can be used for the disinfection of clothing, utensils, skin, etc., and is safe and non-irritating.

Preferably, by mass volume percentage, the above-mentioned sterilizing and disinfecting spray comprises the following components: 10-20% of ethanol, 0.05-0.1% of chloroquine or chloroquine derivative, 9-10% of moisturizing and penetration enhancer, the balance being water and pH adjustment The pH of the disinfectant spray is 6-7.

Preferably, the above-mentioned moisturizing and penetration enhancing agent is one or more of glycerin, polyglycol, and lauryl ketone.

Preferably, the above pH adjusting agent is citric acid, tartaric acid or acetic acid.

As a kind of preferably, the above-mentioned sterilization and disinfection spray is prepared from the method comprising the following steps:

S1. chloroquine phosphate is dissolved in water to obtain an aqueous solution of chloroquine phosphate;

S2. the moisturizing and penetration enhancing agent is added to the chloroquine phosphate aqueous solution, and stirring is uniform;

S3. feed ethanol according to the proportion, and add the remaining water, stir evenly;

S4. adding a pH regulator to adjust the pH of the solution, and canning to obtain the sterilizing and disinfecting spray.

In addition, as an optional preferred solution, a sterilizing and disinfecting mouthwash has also been developed based on the sterilizing and disinfecting solution of the present invention, which, in percentage by mass and volume, includes the following components: 10-30% of ethanol, 0.01-1% of chloroquine phosphate, Glycerin 2～8%, Polysorbate 80 0.1～0.5%, Menthol oil 0.02～0.08%, Macrogol 400 0.3～1%, Cyclamate 1～3%, Lemon essence 0.003～0.008%, Purified water balance .

More preferably, by mass volume percentage, the sterilizing and disinfecting mouthwash comprises the following components: 10-20% ethanol, 0.05-0.1% chloroquine phosphate, 2-8% glycerin, 0.1-0.5% polysorbate 80, and peppermint oil 0.02-0.08%, polyethylene glycol 400 0.3-1%, cyclamate 1-3%, lemon essence 0.003-0.008%, and the balance of purified water.

Most preferably, by mass volume percentage, the sterilizing and disinfecting mouthwash comprises the following components: chloroquine phosphate 0.1%, glycerin 5%, polysorbate 80 0.3%, peppermint oil 0.05%, ethanol 20%, polyethylene glycol 400 0.6%, cyclamate 2%, lemon essence 0.005%, and the balance of purified water.

Compared with the prior art, the beneficial effects of the present invention are:

The present invention creatively finds that when low-concentration alcohol is used in combination with lower-dose chloroquine phosphate, its bacteriostatic effect is significantly improved compared with that of low-concentration alcohol or chloroquine phosphate alone, which can make the inhibitory effect of chloroquine phosphate lower at a lower concentration. The bacterial rate is significantly increased to 100%, and the cost is reduced; and the ethanol concentration is low, reducing the potential risks caused by high-concentration alcohol disinfectants.

The invention develops a new field of external application of chloroquine phosphate, uses the old chloroquine phosphate for new use, has a solid clinical safety foundation, and has broad-spectrum, high-efficiency and safe disinfection and sterilization activities, including Escherichia coli, Candida albicans, golden yellow grapes Coccus and other common germs as well as coronavirus, influenza virus, HIV virus, HPV virus, etc., so it has the potential to be used as a common sterilization and disinfectant, and has a good application prospect.

Detailed ways

The present invention is further described below in conjunction with specific embodiments, but the embodiments do not limit the present invention in any form. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the technical field.

Unless otherwise specified, the reagents and materials used in the following examples are commercially available.

Embodiment 1 Different ratios of sterilizing and disinfecting liquids

1. Experimental materials and methods

(1) Samples and bacteria

Chloroquine phosphate standard, Staphylococcus aureus, Candida albicans, and Escherichia coli were purchased from China National Institute for Food and Drug Control; tryptone soy agar medium, tryptone soy liquid medium, Sabouraud dextrose liquid medium, sand Dextrose agar medium, LB agar medium, LB liquid medium, and pH7.0 sodium chloride peptone buffer were purchased from Guangdong Huankai Biological Co., Ltd.; ethanol was medical grade absolute ethanol.

(2) Instruments: biological safety cabinet, biochemical incubator, sterilizer, oven, electronic balance, shaker, PH test paper.

2. Antibacterial test method

(1) Bacterial fluid recovery

Take 200 μl of the frozen original bacterial solution of Staphylococcus aureus into 10 ml of tryptic soy liquid medium, and cultivate at 35°C for 24 hours on a shaker;

Take 200 μl of the frozen original bacterial solution of Candida albicans in Sabouraud dextrose liquid medium, and cultivate at 25°C on a shaker for 48 hours;

Take 200 μl of Escherichia coli frozen original bacterial solution into 10 ml of LB liquid medium, and cultivate at 35°C for 18-24 hours on a shaker;

(2) Preparation of bacterial liquid

Gradient dilution of the final bacterial solution with pH7.0 sodium chloride peptone solution, plate culture of the diluted bacterial solution, 2 replicate plates for each dilution concentration, and tryptic soy agar medium for bacteria, cultured for 3 days, and counted daily. Number of colonies; select the ones that can be read and the data are in the range of 50-100cfu.

(3) Antibacterial test

Take 1 mL of each concentration of disinfectant (as shown in Table 1-Table 3) and inject it into a test tube of nutrient broth medium. Add bacterial solution (1mL/tube) to each test tube.

A positive control group (with bacteria solution, no disinfectant) and a blank control group (pure water, no bacteria solution and no disinfectant) were also set up.

Pipette 100 μL of the liquid in the test tubes of the above groups and spread it evenly on a nutrient agar plate, incubate at 35°C for 18-24 h, count the number of bacteria, observe the results, and calculate the bacteriostatic rate.

2. Test results

Table 1 shows the test results of different concentrations of LK solution or ethanol solution and its bacteriostatic rate.

Table 1

Table 2 and Table 3 are the bactericidal disinfectant of different proportions and the bacteriostatic rate thereof, wherein LK is chloroquine phosphate.

Table 2

table 3

Combined with the results of Table 1-Table 3, it can be seen that the combination of different concentrations of chloroquine phosphate and alcohol can significantly enhance the antibacterial effect, especially when low-concentration alcohol (10-30%) is compounded with low-concentration chloroquine phosphate (0.01- 1%) of bactericidal disinfectant to Escherichia coli, Staphylococcus aureus, Candida albicans inhibition rate can still reach 90 to 100%, has an unexpected bacteriostatic effect, which is not achieved by using low-concentration alcohol or chloroquine phosphate alone. of.

Embodiment 2 Different pH sterilizing and disinfecting solutions

Table 4 is the disinfectant of different pH and its bacteriostatic rate, LK is chloroquine phosphate.

Table 4

As can be seen from the bacteriostatic rate in Table 4, the present invention will have a strong inhibitory effect on Escherichia coli, Staphylococcus aureus and Candida albicans by the sterilizing and disinfecting solution prepared by compounding chloroquine phosphate with low-concentration alcohol under acidic conditions, The antibacterial rate can reach 99-100%.

Embodiment 3 Sterilization and disinfection spray

A sterilizing and disinfecting spray comprises 10% of ethanol, 0.05% of chloroquine phosphate, 9% of glycerin, and the balance of water, the pH of which is adjusted to 6 by tartaric acid.

The preparation method of above-mentioned sterilizing and disinfecting spray is as follows:

S1. chloroquine phosphate is dissolved in water to obtain an aqueous solution of chloroquine phosphate;

S2. glycerol is added to the chloroquine phosphate aqueous solution, stirred evenly;

S3. feed ethanol according to the proportion, and add the remaining amount of water, and stir evenly;

S4. adding tartaric acid to adjust the pH of the solution, and canning to obtain the sterilizing and disinfecting spray.

The bacteriostatic test results show that the bacteriostatic rate of the sterilizing and disinfecting spray to Escherichia coli, Staphylococcus aureus and Candida albicans can reach 99-100%.

Embodiment 4 Sterilization and disinfection spray

A sterilizing and disinfecting spray comprises 10% of ethanol, 0.1% of chloroquine phosphate, 10% of polyglycol, and the balance is water, and its pH is adjusted to 7 by citric acid.

The preparation method of above-mentioned sterilizing and disinfecting spray is as follows:

S1. chloroquine phosphate is dissolved in water to obtain an aqueous solution of chloroquine phosphate;

S2. Polyglycol is added to the chloroquine phosphate aqueous solution, stirring is uniform;

S3. feed ethanol according to the proportion, and add the remaining amount of water, and stir evenly;

S4. adding citric acid to adjust the pH of the solution, and canning to obtain the sterilizing and disinfecting spray.

The bacteriostatic test results show that the sterilizing and disinfecting spray prepared above also has a strong inhibitory effect on Escherichia coli, Staphylococcus aureus and Candida albicans, and the bacteriostatic rates all reach 99-100%.

Embodiment 5 Sterilization and disinfection spray

A sterilizing and disinfecting spray comprises 20% of ethanol, 0.05% of chloroquine phosphate, 9% of lauryl ketone, and the balance is water, and its pH is adjusted to 6 by acetic acid.

The preparation method of above-mentioned sterilizing and disinfecting spray is as follows:

S1. chloroquine phosphate is dissolved in water to obtain an aqueous solution of chloroquine phosphate;

S2. Lauryl ketone is added to the chloroquine phosphate aqueous solution, stirred evenly;

S3. feed ethanol according to the proportion, and add the remaining amount of water, and stir evenly;

S4. adding acetic acid to adjust the pH of the solution, and canning to obtain the sterilizing and disinfecting spray.

The bacteriostatic test results show that the sterilizing and disinfecting spray prepared above has a strong inhibitory effect on Escherichia coli, Staphylococcus aureus and Candida albicans, and the bacteriostatic rate reaches 99-100%.

Embodiment 6 Sterilization and disinfection spray

A sterilizing and disinfecting spray comprises 20 percent of ethanol, 0.01 percent of chloroquine phosphate, 9 percent of glycerin, and the balance of water, and its pH is adjusted to 6 by tartaric acid.

The preparation method of above-mentioned sterilizing and disinfecting spray is as follows:

S1. chloroquine phosphate is dissolved in water to obtain an aqueous solution of chloroquine phosphate;

S2. glycerol is added to the chloroquine phosphate aqueous solution, and stirred evenly;

S3. feed ethanol according to the proportion, and add the remaining amount of water, and stir evenly;

S4. adding tartaric acid to adjust the pH of the solution, and canning to obtain the sterilizing and disinfecting spray.

The bacteriostatic test results show that the bacteriostatic rate of the sterilizing and disinfecting spray to Escherichia coli, Staphylococcus aureus and Candida albicans can reach 99-100%.

Embodiment 7 A kind of antibacterial mouthwash

A bacteriostatic mouthwash comprising the components in Table 5.

table 5

Element mass to volume ratio Chloroquine Phosphate 0.05% glycerin 5% Polysorbate 80 0.3% Peppermint Oil 0.05% Ethanol 10% polyethylene glycol 400 0.6% Cyclamate 2% Lemon Essence 0.005% purified water margin

The antibacterial test results show that the mouthwash of the above formula has a strong inhibitory effect on Escherichia coli, Staphylococcus aureus and Candida albicans, and the antibacterial rates are 99.57%, 80.97% and 100% respectively.

Embodiment 8 A kind of antibacterial mouthwash

A bacteriostatic mouthwash comprising the components in Table 6.

Table 6

Element mass to volume ratio Chloroquine Phosphate 0.1% glycerin 5% Polysorbate 80 0.3% Peppermint Oil 0.05% Ethanol 20% polyethylene glycol 400 0.6% Cyclamate 2% Lemon Essence 0.005% purified water margin

The antibacterial test results show that the mouthwash of the above formula has a strong inhibitory effect on Escherichia coli, Staphylococcus aureus and Candida albicans, and the antibacterial rates are 100%, 98.97% and 100% respectively.

The above-mentioned embodiments only represent part of the embodiments of the present invention, and the descriptions thereof are specific and detailed, but should not be construed as limiting the scope of the patent of the present invention. It should be pointed out that for those skilled in the art, without departing from the concept of the present invention, several changes and improvements can be made, which all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention should be subject to the appended claims.

Claims (10)

1. The low-concentration alcohol sterilization disinfectant containing chloroquine is characterized by comprising the following components in percentage by mass: 0.01-1% of chloroquine or chloroquine derivative, 10-30% of ethanol and the balance of water.

2. The sterilizing and disinfecting liquid of claim 1, wherein the sterilizing and disinfecting liquid comprises the following components: 0.01-0.8% of chloroquine or chloroquine derivatives, 10-20% of ethanol and the balance of water.

3. The sterilizing and disinfecting liquid of claim 1, wherein the sterilizing and disinfecting liquid comprises the following components: 0.01-0.5% of chloroquine or chloroquine derivatives, 10-20% of ethanol and the balance of water.

4. The sterilizing and disinfecting liquid of claim 1, wherein the sterilizing and disinfecting liquid comprises the following components: 0.05-0.5% of chloroquine or chloroquine derivatives, 20% of ethanol and the balance of water.

5. The disinfectant liquid according to any one of claims 1 to 4, wherein the chloroquine derivative is one or more of chloroquine phosphate, hydroxychloroquine, chloroquine sulfate and chloroquine hydrochloride.

6. The use of the disinfectant liquid according to any one of claims 1 to 4 for the preparation of a disinfectant product.

7. The sterilization and disinfection spray is characterized by comprising the following components in percentage by mass: 10-30% of ethanol, 0.01-1% of chloroquine or chloroquine derivatives, 9-12% of a moisturizing penetration enhancer, the balance of water and a pH regulator, wherein the pH of the disinfection spray is 4-7.

8. The sterilization and disinfection spray as claimed in claim 7, which comprises the following components by mass volume percent: 10-20% of ethanol, 0.05-0.1% of chloroquine or chloroquine derivatives, 9-10% of a moisturizing penetration enhancer, the balance of water and a pH regulator, wherein the pH of the disinfection spray is 6-7.

9. The sterilizing and disinfecting mouthwash is characterized by comprising the following components in percentage by mass and volume: 10-30% of ethanol, 0.01-1% of chloroquine phosphate, 2-8% of glycerol, 800.1-0.5% of polysorbate, 0.02-0.08% of dementholized peppermint oil, 4000.3-1% of polyethylene glycol, 1-3% of sodium cyclamate, 0.003-0.008% of lemon essence and the balance of purified water.

10. The mouthwash according to claim 9, comprising the following components in percentage by mass and volume: 10-20% of ethanol, 0.01-0.1% of chloroquine phosphate, 2-8% of glycerol, 800.1-0.5% of polysorbate, 0.02-0.08% of dementholized peppermint oil, 4000.3-1% of polyethylene glycol, 1-3% of sodium cyclamate, 0.003-0.008% of lemon essence and the balance of purified water.