CN111328811B - Low-concentration alcohol sterilization disinfectant and application thereof - Google Patents

Low-concentration alcohol sterilization disinfectant and application thereof Download PDF

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CN111328811B
CN111328811B CN202010298650.4A CN202010298650A CN111328811B CN 111328811 B CN111328811 B CN 111328811B CN 202010298650 A CN202010298650 A CN 202010298650A CN 111328811 B CN111328811 B CN 111328811B
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chloroquine
sterilizing
ethanol
balance
disinfectant
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CN111328811A (en
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王建瑜
李相玲
刘琦
宁华梅
王婷
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Guangzhou Hybribio Technology Co ltd
Guangzhou Kaipu Pharmaceutical Technology Co ltd
Guangzhou Health Medical Technology Co ltd
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Guangzhou Kaipu Pharmaceutical Technology Co ltd
Guangzhou Health Medical Technology Co ltd
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    • AHUMAN NECESSITIES
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    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
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    • AHUMAN NECESSITIES
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Abstract

The invention discloses a low-concentration alcohol sterilization disinfectant and application thereof. The sterilizing disinfectant comprises 0.01-1% of chloroquine or chloroquine derivatives and 10-30% of ethanol. The sterilizing disinfectant is compounded by low-concentration alcohol and chloroquine phosphate, has obvious synergistic effect, can obviously increase the bacteriostasis rate to 100 percent under the lower concentration of the chloroquine phosphate, has low concentration of the alcohol, has broad-spectrum, high-efficiency and safe sterilizing activity, and can be further developed into antibacterial sterilizing products of various dosage forms, so the sterilizing disinfectant has great potential to be used as a common, safe and high-efficiency sterilizing disinfectant, and has good application prospect.

Description

Low-concentration alcohol sterilization disinfectant and application thereof
Technical Field
The invention relates to the technical field of disinfection and protection. More particularly relates to a low-concentration alcohol sterilization disinfectant and application thereof.
Background
Chloroquine phosphate is an antimalarial drug which has been clinically used for over seventy years, and the past research has clearly suggested that the chloroquine phosphate not only has antimalarial effect, but also has broad-spectrum antiviral effect. And no research and report on chloroquine washing and caring products related to external disinfection and bacteriostasis are provided aiming at the daily bacteriostatic and disinfectant requirements for external washing and caring.
In addition, among the existing numerous disinfection products, alcohol is widely applied to daily life, particularly to the medical industry as the most common disinfectant. The alcohol can be used for disinfection because it can absorb the water content of bacterial protein, make it dehydrate, denature and solidify so as to attain the goal of killing bacteria. Meanwhile, the strength of the sterilization and disinfection capacity of the alcohol has a direct relation with the concentration, and the alcohol cannot be too high or too low, if high-concentration alcohol is used, the bacterial protein is dehydrated too quickly, so that the protein on the surface of the bacteria is firstly denatured and solidified to form a firm coating, and the alcohol cannot well permeate into the bacteria instead, so that the sterilization capacity of the bacteria is influenced; therefore, 70% -75% alcohol is generally used in the medical field, which can solidify the protein composing the bacteria, can not form a coating, can continuously permeate the alcohol to the inside to completely sterilize and disinfect the bacteria, wherein the 75% alcohol has the strongest bactericidal power and similar osmotic pressure with the bacteria, can gradually permeate into the bacteria before the protein on the surface of the bacteria is not denatured, dehydrates and denaturates and solidifies all the proteins of the bacteria, and finally kills the bacteria, for example, 75% alcohol can kill escherichia coli, staphylococcus aureus, candida albicans, pseudomonas aeruginosa and the like within one minute at normal temperature; and almost no bacteriostatic effect is achieved when the alcohol concentration is as low as about 30 percent.
However, long-term use of high-concentration alcohol for skin disinfection has certain irritation to the skin. Furthermore, the research investigation conducted by Science relative Medicine found that bacteria are more and more resistant to skin alcohol, and the research found that enterococcus faecium is more and more resistant to high concentration alcohol, and that this increased resistance caused bacteria to survive longer after contacting alcohol; in addition, studies have shown that vancomycin-resistant enterococci also begin to adapt to alcohol, and the DNA of alcohol-resistant bacteria is mutated at specific genetic positions associated with cellular metabolism, and resistance to alcohol appears to have a complex genetic basis as well as resistance to antibiotics. Therefore, the method has potential risk by completely depending on the alcohol disinfectant with higher concentration, seeks an external disinfection and washing product with better antibacterial effect, higher safety and no stimulation, and has important application value for medical disinfection, daily disinfection and prevention and control of virus epidemic situation.
Disclosure of Invention
The invention aims to provide an external disinfection cleaning and protecting product which is safe, non-irritant and remarkable in bacteriostatic effect. The research of the invention shows that the external application of chloroquine phosphate has obvious sterilization and disinfection effects and certain dose dependence, the lower concentration of chloroquine phosphate is compounded with low concentration alcohol (the mass concentration is below 30 percent), the bacteriostasis effect can be obviously improved, the combination of the two has unexpected synergistic effect, the bacteriostasis rate is obviously improved to 100 percent, the product has broad-spectrum, high-efficiency and safe sterilization and disinfection activities, and can be further developed into bacteriostatic and disinfectant products of various formulations, thereby having great potential to be used as a common, safe and high-efficiency sterilization and disinfection agent.
The invention aims to provide a chloroquine-containing sterilizing disinfectant.
The invention also aims to provide the application of the sterilizing and disinfecting liquid in preparing sterilizing and disinfecting products.
Still another object of the present invention is to provide a germicidal disinfectant spray.
Still another object of the present invention is to provide a sterilizing mouthwash.
In order to achieve the purpose, the invention is realized by the following scheme:
the invention provides a sterilizing disinfectant, which comprises the following components in percentage by mass (w/v): 0.01-1% of chloroquine or chloroquine derivative, 10-30% of ethanol and the balance of water.
The sterilizing disinfectant disclosed by the invention can obviously enhance the bacteriostatic and bactericidal effects of low-concentration alcohol or chloroquine by reasonably compounding the low-concentration alcohol and the chloroquine, and can effectively reduce the probability of generating resistance to alcohol by bacteria because the alcohol concentration is low, the irritation is avoided, the safety performance is high and the bacteriostatic effect is obviously improved.
Preferably, the sterilizing and disinfecting liquid comprises the following components in percentage by mass and volume: 0.01-0.8% of chloroquine or chloroquine derivatives, 10-20% of ethanol and the balance of water.
Preferably, the sterilizing and disinfecting liquid comprises the following components in percentage by mass and volume: 0.01-0.5% of chloroquine or chloroquine derivatives, 10-20% of ethanol and the balance of water.
Preferably, the sterilizing and disinfecting liquid comprises the following components in percentage by mass and volume: 0.05-0.5% of chloroquine or chloroquine derivatives, 10-20% of ethanol and the balance of water.
Preferably, the sterilizing and disinfecting liquid comprises the following components in percentage by mass and volume: 0.05-0.1% of chloroquine or chloroquine derivatives, 10-20% of ethanol and the balance of water.
More preferably, the sterilizing and disinfecting liquid comprises the following components in percentage by volume by mass: 0.1% of chloroquine or chloroquine derivative, 20% of ethanol and the balance of water.
Preferably, the chloroquine derivative is one or more of chloroquine phosphate, hydroxychloroquine, chloroquine sulfate and chloroquine hydrochloride.
The invention also requests to protect the application of the sterilizing disinfectant in preparing sterilizing and disinfecting products. The sterilization and disinfection products comprise various formulations of sterilization and disinfection agents, mouthwash with sterilization and disinfection functions, hand sanitizer and the like.
As a selectable preferred scheme, based on the sterilization disinfectant, the invention also develops a sterilization and disinfection spray, which comprises 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.
The sterilization and disinfection spray can be used for disinfecting clothes, appliances, skin and the like, and is safe and non-irritant.
Preferably, the sterilizing and disinfecting spray comprises the following components in percentage by mass: 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.
Preferably, the moisture-retention penetration enhancer is one or more of glycerol, polyglycol and laurocapram.
Preferably, the pH adjuster is citric acid, tartaric acid or acetic acid.
Preferably, the disinfectant and disinfection spray is prepared by the method comprising the following steps:
s1, adding water to chloroquine phosphate for dissolving to obtain a chloroquine phosphate aqueous solution;
s2, adding the moisturizing penetration enhancer into the chloroquine phosphate aqueous solution, and uniformly stirring;
s3, feeding ethanol according to a proportion, adding the rest water, and uniformly stirring;
and S4, adding a pH regulator to regulate the pH value of the solution, and canning to obtain the sterilization and disinfection spray.
In addition, as an optional preferred scheme, the sterilizing and disinfecting mouth wash is developed based on the sterilizing and disinfecting liquid, and comprises the following components in percentage by mass: 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.
More preferably, the germicidal disinfectant mouthwash comprises the following components in percentage by mass volume: 10-20% of ethanol, 0.05-0.1% 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.
Most preferably, the germicidal disinfectant mouthwash comprises the following components in percentage by mass volume: 0.1% of chloroquine phosphate, 5% of glycerol, 800.3% of polysorbate, 0.05% of dementholized peppermint oil, 20% of ethanol, 4000.6% of polyethylene glycol, 2% of sodium cyclamate, 0.005% of lemon essence and the balance of purified water.
Compared with the prior art, the invention has the beneficial effects that:
the invention creatively discovers that the bacteriostatic effect of the low-concentration alcohol and the lower-dose chloroquine phosphate is remarkably improved compared with that of the single low-concentration alcohol or the single chloroquine phosphate, the bacteriostatic rate can be remarkably improved to 100 percent under the lower concentration of the chloroquine phosphate, and the cost is reduced; and the ethanol concentration is low, so that the potential risk brought by high-concentration alcohol disinfectant is reduced.
The invention develops a new external application field of chloroquine phosphate, and the new application of the old chloroquine phosphate has a solid clinical safety foundation, has broad-spectrum, high-efficiency and safe disinfection and sterilization activity, and comprises common pathogenic bacteria, influenza virus, HIV virus, HPV virus and the like such as escherichia coli, candida albicans, staphylococcus aureus and the like, so that the new chloroquine phosphate has the potential to be used as a common disinfectant and has good application prospect.
Detailed Description
The present invention is further illustrated by the following specific examples, which are not intended to limit the invention in any way. Reagents, methods and apparatus used in the present invention are conventional in the art unless otherwise indicated.
Unless otherwise indicated, reagents and materials used in the following examples are commercially available.
Example 1 different proportions of sterilizing and disinfecting solutions
1. Experimental materials and methods
(1) Samples and pathogens
The chloroquine phosphate standard, staphylococcus aureus, candida albicans and escherichia coli are purchased from China food and drug testing research institute; tryptone soy peptone agar medium, tryptone soy peptone liquid medium, Sa's glucose agar medium, LB liquid medium, pH7.0 sodium chloride peptone buffer were purchased from Guangdong Huaqiao biology GmbH; the ethanol is medical grade absolute ethanol.
(2) The instrument comprises the following steps: biological safety cabinet, biochemical incubator, sterilizer, oven, electronic balance, shaking table, PH test paper.
2. Bacteriostatic test method
(1) Recovery of bacterial liquid
Respectively taking 200 mul of staphylococcus aureus frozen original bacterial liquid into 10ml of trypticase soybean liquid culture medium, and carrying out shake culture at 35 ℃ for 24 hours;
taking 200 mul of candida albicans frozen original bacterial liquid, putting the candida albicans frozen original bacterial liquid into a Sabouraud's dextrose liquid culture medium, and carrying out shake culture at 25 ℃ for 48 hours;
respectively taking 200 mul of escherichia coli frozen original bacterial liquid into 10ml of LB liquid culture medium, and carrying out shake cultivation at 35 ℃ for 18-24 hours;
(2) preparation of bacterial liquid
Diluting the final bacterial liquid by using a sodium chloride peptone solution with the pH value of 7.0 in a gradient manner, performing plate culture on the diluted bacterial liquid, performing plate culture on each diluted concentration by using 2 repeated plates, culturing the bacteria by using a trypticase aged soybean agar medium for 3 days, and counting the number of bacterial colonies day by day; selecting readable data with the data in the range of 50-100 cfu.
(3) Experiment for inhibiting bacteria
1mL of each concentration of disinfectant (see Table 1-Table 3) was poured into 1 tube of nutrient broth. Bacterial suspension (1 mL/tube) was added to each tube.
A positive control group (adding bacteria liquid and not adding disinfectant) and a blank control group (adding pure water, not adding bacteria liquid and not adding disinfectant) are additionally arranged.
And (3) sucking 100 mu L of liquid in each group of test tubes, uniformly coating the liquid on a nutrient agar plate, culturing for 18-24 h at 35 ℃, calculating the number of bacteria, observing the result and calculating the bacteriostasis rate.
2. Test results
Table 1 shows the results of testing LK solutions or ethanol solutions with different concentrations and their bacteriostatic ratios.
TABLE 1
Figure GDA0003016308970000051
Figure GDA0003016308970000061
Tables 2 and 3 show the sterilizing disinfectant and the bacteriostatic rate thereof in different proportions, wherein LK is chloroquine phosphate.
TABLE 2
Figure GDA0003016308970000062
TABLE 3
Figure GDA0003016308970000071
The results shown in tables 1 to 3 are combined for analysis, so that the inhibition effect of the chloroquine phosphate and the alcohol with different concentrations can be remarkably enhanced, particularly, when the low-concentration alcohol (10-30%) is compounded with the low-concentration chloroquine phosphate (0.01-1%), the inhibition rate of the sterilization disinfectant on escherichia coli, staphylococcus aureus and candida albicans can still reach 90-100%, and the unexpected inhibition effect is achieved, and the inhibition effect cannot be achieved by singly using the low-concentration alcohol or the chloroquine phosphate.
EXAMPLE 2 Sterilization/Disinfection solutions with different pH values
Table 4 shows the disinfectant solutions with different pH values and the bacteriostatic ratios thereof, and LK is chloroquine phosphate.
TABLE 4
Figure GDA0003016308970000072
Figure GDA0003016308970000081
As can be seen from the bacteriostasis rates in Table 4, the sterilizing disinfectant prepared by compounding low-concentration alcohol with chloroquine phosphate has a strong inhibiting effect on escherichia coli, staphylococcus aureus and candida albicans under an acidic condition, and the bacteriostasis rate can reach 99-100%.
Example 3 Disinfection spray
A sterilization and disinfection spray comprises 10% of ethanol, 0.05% of chloroquine phosphate, 9% of glycerol and the balance of water, and the pH value of the sterilization and disinfection spray is adjusted to 6 by tartaric acid.
The preparation method of the sterilization and disinfection spray comprises the following steps:
s1, adding water to chloroquine phosphate for dissolving to obtain a chloroquine phosphate aqueous solution;
s2, adding glycerol into a chloroquine phosphate aqueous solution, and uniformly stirring;
s3, feeding ethanol according to a proportion, adding the balance of water, and uniformly stirring;
s4, adding tartaric acid to adjust the pH value of the solution, and canning to obtain the sterilization and disinfection spray.
The bacteriostasis test result shows that the bacteriostasis rate of the sterilization and disinfection spray to escherichia coli, staphylococcus aureus and candida albicans can reach 99-100%.
Example 4 Disinfection spray
A sterilization and disinfection spray comprises 10% of ethanol, 0.1% of chloroquine phosphate, 10% of polyglycol and the balance of water, and the pH value of the sterilization and disinfection spray is adjusted to 7 by citric acid.
The preparation method of the sterilization and disinfection spray comprises the following steps:
s1, adding water to chloroquine phosphate for dissolving to obtain a chloroquine phosphate aqueous solution;
s2, adding polyglycol into a chloroquine phosphate aqueous solution, and uniformly stirring;
s3, feeding ethanol according to a proportion, adding the balance of water, and uniformly stirring;
and S4, adding citric acid to adjust the pH value of the solution, and canning to obtain the sterilizing and disinfecting spray.
The bacteriostasis test result shows that the prepared sterilization and disinfection spray also has strong inhibition effect on escherichia coli, staphylococcus aureus and candida albicans, and the bacteriostasis rate reaches 99-100%.
Example 5 Disinfection spray
A sterilization and disinfection spray comprises 20% of ethanol, 0.05% of chloroquine phosphate, 9% of laurocapram and the balance of water, and the pH value of the sterilization and disinfection spray is adjusted to 6 by acetic acid.
The preparation method of the sterilization and disinfection spray comprises the following steps:
s1, adding water to chloroquine phosphate for dissolving to obtain a chloroquine phosphate aqueous solution;
s2, adding laurocapram into a chloroquine phosphate aqueous solution, and uniformly stirring;
s3, feeding ethanol according to a proportion, adding the balance of water, and uniformly stirring;
and S4, adding acetic acid to adjust the pH value of the solution, and canning to obtain the sterilizing and disinfecting spray.
The bacteriostatic test result shows that the prepared sterilizing and disinfecting spray has a strong inhibiting effect on escherichia coli, staphylococcus aureus and candida albicans, and the bacteriostatic rate reaches 99-100%.
Example 6 Disinfection spray
A disinfecting spray is prepared from alcohol (20%), chloroquine phosphate (0.01%), glycerin (9%), and water (the pH value of which is regulated to 6) by tartaric acid.
The preparation method of the sterilization and disinfection spray comprises the following steps:
s1, adding water to chloroquine phosphate for dissolving to obtain a chloroquine phosphate aqueous solution;
s2, adding glycerol into a chloroquine phosphate aqueous solution, and uniformly stirring;
s3, feeding ethanol according to a proportion, adding the balance of water, and uniformly stirring;
s4, adding tartaric acid to adjust the pH value of the solution, and canning to obtain the sterilization and disinfection spray.
The bacteriostasis test result shows that the bacteriostasis rate of the sterilization and disinfection spray to escherichia coli, staphylococcus aureus and candida albicans can reach 99-100%.
Example 7A bacteriostatic mouth wash
A bacteriostatic mouth wash comprises the components in table 5.
TABLE 5
Figure GDA0003016308970000091
Figure GDA0003016308970000101
The bacteriostatic test result shows that the mouthwash of the formula has a strong inhibitory effect on escherichia coli, staphylococcus aureus and candida albicans, and the bacteriostatic rates are 99.57%, 80.97% and 100% respectively.
Example 8A bacteriostatic mouthwash
A bacteriostatic mouth wash comprises the components in table 6.
TABLE 6
Composition (I) Mass to volume ratio
Chloroquine phosphate 0.1%
Glycerol 5%
Polysorbate 80 0.3%
Peppermint oil 0.05%
Ethanol 20%
Polyethylene glycol 400 0.6%
Sodium cyclamate 2%
Lemon essence 0.005%
Purified water Balance of
The bacteriostatic test result shows that the mouthwash of the formula has a strong inhibitory effect on escherichia coli, staphylococcus aureus and candida albicans, and the bacteriostatic rates are 100%, 98.97% and 100% respectively.
The above examples only represent some embodiments of the present invention, and the description thereof is more specific and detailed, but not to be construed as limiting the scope of the present invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.

Claims (9)

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 derivatives, 10-30% of ethanol and the balance of water;
the chloroquine derivative is one or more of chloroquine phosphate, hydroxychloroquine, chloroquine sulfate and chloroquine hydrochloride.
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 use of the disinfectant liquid according to any one of claims 1 to 4 for the preparation of a disinfectant product.
6. 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; the chloroquine derivative is one or more of chloroquine phosphate, hydroxychloroquine, chloroquine sulfate and chloroquine hydrochloride.
7. The sterilization and disinfection spray as claimed in claim 6, 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.
8. 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.
9. The mouthwash according to claim 8, which comprises 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.
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