CN116617254A - Anti-pathogenic microorganism composition containing boric acid and nitrite and application thereof - Google Patents

Anti-pathogenic microorganism composition containing boric acid and nitrite and application thereof Download PDF

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CN116617254A
CN116617254A CN202310588696.3A CN202310588696A CN116617254A CN 116617254 A CN116617254 A CN 116617254A CN 202310588696 A CN202310588696 A CN 202310588696A CN 116617254 A CN116617254 A CN 116617254A
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boric acid
nitrite
acid
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袁鑫
陈文腾
黄张建
杜雨棽
钟秀文
李雨婷
朱琪
刘祖东
俞永平
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Hangzhou Zehnder Medical Technology Co ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/22Boron compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0014Skin, i.e. galenical aspects of topical compositions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10Antimycotics
    • AHUMAN NECESSITIES
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    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
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    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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Abstract

The invention provides an antipathogenic microorganism composition containing boric acid and nitrite and application thereof. The composition is a non-antibiotic, and the active ingredients of the composition respectively comprise boric acid and nitrite, wherein the composition shows that pathogenic microorganisms such as antivirus, bacteria, fungi and the like have synergistic effect, so that the pathogenic microorganisms are eradicated, and the composition can be used for preventing and treating diseases caused by various pathogenic microorganisms. The invention provides a broad-spectrum antipathogenic microorganism composition which can inhibit the growth and/or eradication of various pathogenic microorganisms including viruses, bacteria, fungi and the like, and can be used for preparing medicines for preventing and treating infectious diseases caused by various pathogenic microorganisms.

Description

Anti-pathogenic microorganism composition containing boric acid and nitrite and application thereof
The application number is 202211176204.1, the application date is 2022.9.26, and the invention name is an antipathogenic microorganism composition containing boric acid and nitrite and a divisional application of the composition.
Technical Field
The invention belongs to the field of pharmacy, and relates to an antipathogenic microorganism composition containing boric acid and nitrite, and a preparation method and application thereof.
Background
Pathogenic microorganisms such as viruses, bacteria, fungi and the like can form infection after invading a human body, and diseases such as pneumonia, warts, ulcers, herpes, tinea, acne, conjunctivitis, hand-foot-mouth disease, eczema and the like can be caused by the infection, and the infection diffusion can be aggravated by untimely intervention and prevention, so that the personal health and the public health safety of society are greatly endangered. External environmental disinfection is commonly performed by using alcohol, 84 disinfectant and the like to block infection and transmission of pathogenic microorganisms. The most important means in clinic is to use specific antiviral drugs or antibiotic drugs to control infection for the corresponding disease treatment caused by the pathogenic microorganisms, but long-term repeated use of such antipathogenic microorganism agents is extremely easy to induce drug resistance, and the drug resistant pathogenic microorganisms can further acquire multiple drug resistance and are also the main cause of causing the fatal microorganism infection. The main means for solving the drug resistance of pathogenic microorganisms in the past is to improve the original antibiotics/antiviral drugs or discover new antibiotics/new antiviral drugs, but the obtained results can not meet the clinical demands, and the new antibiotics/new antiviral drugs also face the drug resistance of pathogenic microorganisms. In addition, most infectious diseases are caused by a variety of pathogenic microorganisms, such as viral infections combined with infection by pathogenic microorganisms such as bacteria and fungi, are clinically common complications, and treatment regimens directed against only one pathogenic microorganism, i.e., one source of infection, tend to be limited in effectiveness. There is therefore a need to develop non-antibiotic, highly effective, broad spectrum agents against a variety of pathogenic microorganisms for the treatment and prevention of infectious diseases.
Disclosure of Invention
In order to solve the above problems, an object of the present invention is to provide an antipathogenic microorganism composition comprising boric acid, nitrite, the composition consisting of a first component and a second component, the first component consisting of 0.02 to 10.0w% of boric acid and 90.0 to 99.98w% of an excipient; the second component consists of 0.02-8.0 w% nitrite and 92.0-99.98 w% excipient.
Preferably, the nitrite is one or more of sodium nitrite and potassium nitrite.
Further preferably, the first component of the antipathogenic microbial composition of the invention comprises 0.02 to 8.0w% boric acid and the second component comprises 0.02 to 6.0w% nitrite.
Further preferably, the first component of the antipathogenic microbial composition of the invention comprises 0.1 to 6.0w% boric acid and the second component comprises 0.02 to 4.0w% nitrite.
Further preferably, the first component of the antipathogenic microbial composition of the invention comprises 0.2 to 4.0w% boric acid and the second component comprises 0.1 to 4.0w% nitrite.
Further preferably, the first component of the antipathogenic microbial composition of the invention comprises 0.5 to 4.0w% boric acid and the second component comprises 0.4 to 4.0w% nitrite.
Further preferably, the first component of the antipathogenic microbial composition of the invention comprises 6.0w% boric acid and the second component comprises 3.0w% nitrite.
Further preferably, the first component of the antipathogenic microbial composition of the invention comprises 4.0w% boric acid and the second component comprises 1.0w% nitrite.
Further preferably, the first component of the antipathogenic microbial composition of the invention comprises 4.0w% boric acid and the second component comprises 0.9w% nitrite.
Further preferably, the antipathogenic microorganism composition of the invention comprises 3.0w% boric acid in the first component and 6.0w% nitrite in the second component.
Further preferably, the antipathogenic microorganism composition of the invention comprises 3.0w% boric acid in the first component and 4.0w% nitrite in the second component.
Further preferably, the first component of the antipathogenic microbial composition of the invention comprises 2.0w% boric acid and the second component comprises 2.0w% nitrite.
Further preferably, the first component of the antipathogenic microbial composition of the invention comprises 2.0w% boric acid and the second component comprises 1.0w% nitrite.
Further preferably, the first component of the antipathogenic microbial composition of the invention comprises 2.0w% boric acid and the second component comprises 0.4w% nitrite.
Further preferably, the first component of the antipathogenic microbial composition of the invention comprises 2.0w% boric acid and the second component comprises 0.1w% nitrite.
Further preferably, the first component of the antipathogenic microbial composition of the invention comprises 2.0w% boric acid and the second component comprises 0.02w% nitrite.
Further preferably, the first component of the antipathogenic microbial composition of the invention comprises 0.2w% boric acid and the second component comprises 0.02w% nitrite.
Further preferably, the first component of the antipathogenic microbial composition of the invention comprises 0.1w% boric acid and the second component comprises 0.02w% nitrite.
Further preferably, the first component of the antipathogenic microbial composition of the invention comprises 0.02w% boric acid and the second component comprises 0.02w% nitrite.
Further preferably, the first component of the antipathogenic microbial composition of the invention comprises 0.5w% boric acid and the second component comprises 0.5w% nitrite.
Excipients included in the antipathogenic microbial compositions of the invention include, but are not limited to, one or more of solvents, diluents, wetting agents, antioxidants, chelating agents, emulsifiers, preservatives, antibacterial agents, opacifiers, colorants, gelling agents, flavoring agents, pH adjusters, thickening agents and other suitable oily and aqueous substances.
The excipient in the antipathogenic microbial composition of the invention comprises a viscosity thickener present in the composition in an amount of 0.3 to 0.6w% of the composition.
The viscosity thickener comprises one or more, including but not limited to, polyacrylic acid polymers, such as polyacrylic acid, polyacrylate polymers; cellulose ethers such as hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, methyl cellulose, carboxymethyl cellulose and sodium carboxymethyl cellulose; copolymers of methyl vinyl ether and maleic anhydride; carbomers; gums such as sodium alginate, xanthan gum or chitosan.
The excipients in the antipathogenic microbial compositions of the invention comprise a wetting agent present in the composition in an amount of from 10% to 30% by weight of the composition.
The humectant comprises one or more, including but not limited to glycerin or propylene glycol.
The excipient in the antipathogenic microbial composition of the invention comprises a preservative present in the composition in an amount of 0.1w% of the composition.
The preservative comprises one or more, including but not limited to sorbic acid, benzoic acid, or ethyl paraben.
The excipient in the antipathogenic microbial composition of the invention comprises a pH regulator in the composition in an amount of 0.12 to 0.9w% of the first component.
The pH adjustor comprises one or more of a variety of buffer salts including, but not limited to, sodium dihydrogen phosphate, ascorbic acid, salicylic acid, malic acid, lactic acid, citric acid, tartaric acid, various buffer salts such as phosphate buffers, citrate buffers, and the like.
The excipient in the antipathogenic microbial composition of the invention comprises a solvent present in the composition in an amount of more than 50w% of the composition.
The solvent comprises one or more, including but not limited to, physiological saline, sterile water.
The antipathogenic microorganism composition of the invention is prepared by mixing the first component and the second component.
The antipathogenic microorganism composition of the invention comprises 1 part of the first component and 1 part of the second component.
It is another object of the present invention to provide the use of said antipathogenic microbial composition for the preparation of a medicament for the topical treatment and/or prevention of viral, bacterial and/or fungal infections.
The viral, bacterial and/or fungal infections include, but are not limited to, infections caused by influenza, avian influenza, human papilloma virus, coronavirus, herpes zoster virus, herpes simplex virus, enterovirus, coxsackievirus, epox virus, rhinovirus, norovirus, measles virus, molluscum contagiosum virus, staphylococcus aureus, pseudomonas aeruginosa, propionibacterium acnes, escherichia coli, yeast, candida albicans, trichophyton rubrum, salmonella, acinetobacter baumannii, bacillus, methicillin resistant staphylococcus aureus, pseudomonas aeruginosa, and any combination thereof.
The preparation forms of the external medicine of the invention include, but are not limited to, aqueous solution, cream, ointment, emulsion, gel, external liquid, paste, liniment, external powder, aerosol and percutaneous absorption agent.
Such dosage forms are described in the literature (Remington's Pharmaceutical Science,15th Edition,1975.Mack Publishing Company,Easton,Pennsylvania,18042,Chapter 87:Blaug,Seymour) as a prescription for all pharmaceutical chemistry. The principles, classification, preparation and composition of the inactive ingredients of these dosage forms are obvious to the expert in the field of dosage forms and are included in the present invention.
The invention has the beneficial effects that: the composition is a non-antibiotic, and the active ingredients of the composition respectively comprise boric acid and nitrite, wherein the composition shows that pathogenic microorganisms such as antivirus, bacteria, fungi and the like have synergistic effect, so that the pathogenic microorganisms are eradicated, and the composition can be used for preventing and treating diseases caused by various pathogenic microorganisms. The present invention provides a broad spectrum composition of pathogenic microorganisms and a method for preparing the same, which can inhibit the growth and/or eradication of a variety of pathogenic microorganisms including viruses, bacteria, fungi, etc., to prevent and/or treat infectious diseases.
Drawings
FIG. 1 boric acid activity against influenza virus.
FIG. 2 anti-influenza virus activity of various compositions containing boric acid.
Figure 3 anti-influenza virus activity of boric acid in combination with varying concentrations of sodium nitrite.
Figure 4. Antibacterial activity of aqueous formulations containing boric acid, sodium nitrite compositions.
Figure 5. Antifungal activity of aqueous formulations containing boric acid, sodium nitrite compositions.
Figure 6 shows the anti-influenza virus activity of a gel containing boric acid and sodium nitrite composition.
Figure 7 gel containing boric acid, sodium nitrite composition against herpes simplex virus activity.
Detailed Description
The invention will be further described with reference to the drawings and the specific examples. The invention is applicable to the prior art where it is not described. Specific examples of the present invention are given below, but the examples are only for further detailed description of the present invention and do not limit the claims of the present invention.
Example 1: boric acid anti-influenza virus activity
TCID using A/WSN/33 influenza Virus Strain 50 Assay to evaluateAntiviral activity of boric acid at different concentrations, physiological saline served as a blank. Antiviral activity test experimental procedure: different boric acid solutions (directly mixed with virus samples without 1:1 volume dilution) and a blank (normal saline) were prepared with normal saline, the above samples/blank were mixed with influenza A virus at a volume ratio of 9:1, incubated at 25℃for 20min, diluted with stop solution (1:10), and stored at-80 ℃. Taking a mixed solution of a sample and virus, diluting the mixed solution by a culture medium for 20 times and 10 times serial dilution, then taking 100 mu L of detection solution, inoculating the detection solution on a single-layer cell culture plate, inoculating 6 holes for each titer, culturing in an incubator for 3 days, and recording cytopathic conditions to obtain the virus titer TCID 50 The method comprises the steps of carrying out a first treatment on the surface of the Calculation of TCID of sample group and blank control group 50 Difference Δlg=tcid 50 (sample group-blank group). A larger Deltalg value indicates a stronger antiviral activity. A0 < Deltalg<1;B:1≤Δlg<3;C:3≤Δlg<5.5;D:5.5≤Δlg。
TABLE 1 anti-influenza Virus Activity of boric acid alone
Test sample Anti-influenza Virus Activity (Deltalg)
Physiological saline 0
0.05% boric acid solution 0
0.1% boric acid solution 0
0.5% boric acid solution A
1.0% boric acid solution B
1.5% boric acid solution C
2% boric acid solution D
3% boric acid solution D
4% boric acid solution D
5% boric acid solution D
As shown in Table 1, when boric acid was used alone, a dose-dependent effect was observed, and a weak influenza virus inhibitory activity was exhibited at a final concentration of 0.5% and a significant anti-influenza virus activity was exhibited at a final concentration of 1.5% or more, TCID 50 Compared with physiological saline group, is reduced by 10 5.5 More than two times.
Example 2: anti-influenza virus activity of different compositions containing boric acid
TCID using A/WSN/33 influenza Virus Strain 50 The effect of different compositions on the antiviral activity of boric acid was evaluated by the assay, with normal saline as a blank. In this test, sodium chloride, zinc chloride, copper sulfate, sodium nitrite were selected for combination studies, and the two components of the composition were mixed in a volume ratio of 1:1. Experimental procedure reference example 1, A:0 < Deltalg<1;B:1≤Δlg<3;C:3≤Δlg<5.5;D:5.5≤Δlg。
TABLE 2 anti-influenza Virus Activity of different compositions containing boric acid
As a result, as shown in Table 2, when 1% boric acid was used alone, it exhibited a certain inhibitory activity (1. Ltoreq. Deltalg < 3), and when combined with sodium chloride (composition 1), there was no difference in antiviral activity of composition 1. However, when combined with zinc chloride (composition 2) or copper sulfate (composition 3), the influenza virus titer in compositions 2 and 3 was significantly reduced, and the anti-influenza virus activity was superior to that of the boric acid group alone. More importantly, when boric acid is combined with nitrite (composition 4 and composition 5), the anti-influenza virus activity of compositions 4-5 is significantly better than that of composition 2, composition 3 or boric acid alone.
Example 3: anti-influenza virus activity of boric acid combined with sodium nitrite of different concentrations
TCID using A/WSN/33 influenza Virus Strain 50 The antiviral activity of the combination of boric acid and sodium nitrite with different concentrations is evaluated by a detection method, physiological saline is used as a blank control, and the two components of the composition are mixed in a volume ratio of 1:1. Experimental procedure reference example 1, A:0 < Deltalg<1;B:1≤Δlg<3;C:3≤Δlg<5.5;D:5.5≤Δlg。
TABLE 3 anti-influenza Virus Activity of boric acid in combination with sodium nitrite at different concentrations
Test substance Anti-influenza Virus Activity (Deltalg)
Physiological saline 0
1% boric acid B
0.2% sodium nitrite 0
Composition 4:2% boric acid +0.4% sodium nitrite D
0.05% sodium nitrite 0
Composition 6:2% boric acid +0.1% sodium nitrite D
Composition 7:2% boric acid +0.1% potassium nitrite D
0.01% sodium nitrite 0
Composition 8:2% boric acid +0.02% sodium nitrite D
Composition 9:0.2% boric acid +0.02% sodium nitrite D
Composition 10:0.1% boric acid +0.02% sodium nitrite D
Composition 11:0.02% boric acid+0.02% sodium nitrite D
As shown in table 3, sodium nitrite alone at different concentrations (0.01% -0.2%) had no anti-influenza virus activity, and when boric acid was combined with sodium nitrite at different concentrations (0.02% -0.4%) at 1:1, influenza virus titer in the composition was significantly reduced, and anti-influenza virus activity of the composition was superior to that of the 1% boric acid group alone.
Example 4: aqueous antibacterial activity of boric acid and sodium nitrite containing compositions
The antibacterial activity of boric acid and sodium nitrite composition aqueous solution (volume ratio 1:1 mixture) was evaluated using a quantitative sterilization method of staphylococcus aureus (ATCC 6538, supplied by the north narrative biotechnology company, ltd, culture passage 3) and escherichia coli (8099, supplied by the food safety engineering technology research development center, guangdong province, culture passage 3). Taking a sterile test tube, adding a composition sample to be tested, adding a bacterial suspension for test, and rapidly mixing and timing. The bacteria to be tested interacted with the composition for 10 minutes or 30 minutes, 1.0mL of sample liquid is respectively sucked, the number of viable bacteria is measured according to a viable bacteria culture counting method, and each tube of sample liquid is inoculated with 2 plates. If the number of colonies growing on the plate is large, the plate may be serially diluted 10 times with PBS and then subjected to viable bacteria culture counting. Parallel experiments were also performed with PBS as positive control. The number of colonies recovered by positive control was 1.0X10 4 CFU/mL~9.0×10 4 CFU/mL. All test and control samples were incubated at 36.+ -. 1 ℃ and the final results were observed for 48h of bacterial propagule culture. The test was repeated 3 times, and the sterilization rate was calculated.
TABLE 4 antibacterial Activity of aqueous solutions containing boric acid and sodium nitrite compositions
As shown in Table 4, the 2% boric acid alone has only weak bactericidal effect on staphylococcus aureus and escherichia coli, the 0.45% sodium nitrite alone has no obvious bactericidal effect on staphylococcus aureus and escherichia coli, and when the 4% boric acid and the 0.9% sodium nitrite are combined in a ratio of 1:1, the bactericidal effect of the composition 12 is obviously enhanced, and the bactericidal activity of more than 99.9% can be achieved after the composition is acted for 10 min.
Example 5: antifungal activity of aqueous solutions containing boric acid and sodium nitrite compositions
The antifungal activity of the boric acid and sodium nitrite composition (1:1 mixture by volume) was evaluated by quantitative sterilization of the suspension using Candida albicans (ATCC 10231, available from North Narah Biotechnology Co., ltd., culture passage 3), and the final result was observed by culturing Candida albicans for 72 hours in the same experimental procedure as in example 4.
TABLE 5 antifungal Activity of aqueous formulations containing boric acid and sodium nitrite compositions
As shown in Table 5, 2% boric acid alone has only weak bactericidal effect on candida albicans, 0.45% sodium nitrite alone has no obvious bactericidal effect on candida albicans and trichophyton rubrum, and when 2% boric acid and 0.45% sodium nitrite are combined, the bactericidal effect of the composition 12 is obviously enhanced, and the bactericidal activity of more than 99.9% can be achieved after 10 minutes of action.
Example 6: preparation of hydrogel containing boric acid and sodium nitrite composition
TABLE 6 exemplary hydrogel formulations containing boric acid
The preparation process comprises the following steps: according to the proportions shown in table 6, hydroxyethyl cellulose was taken and added with water to dissolve completely, then glycerin and boric acid were added, and after the mixture was mixed and stirred to dissolve completely, ethylparaben and a pH adjuster (ph=4 to 5) were added, and stirring was continued for 5 hours, and the gel became clear and transparent after standing for 24 hours.
TABLE 7 exemplary hydrogels with sodium nitrite
Composition of the components NA-01 NA-02 NA-03 NA-04 NA-05 NA-06
Hydroxyethyl cellulose 0.6% 0.6% 0.3% 0.5% 0.6% 0.6%
Glycerol 15% 15% 10% 10% 15% 15%
Sodium nitrite 1.0% 6.0% 4.0% 2.0% 1% 0.5%
Methyl paraben 0.1% 0.1% 0.1% 0.1% 0.1% 0.1%
Purified water Allowance of Allowance of Allowance of Allowance of Allowance of Allowance of
The preparation process comprises the following steps: according to the proportions shown in Table 7, hydroxyethyl cellulose was taken and added with water to be completely dissolved, then sodium nitrite was added, and after the mixture was mixed and stirred to be completely dissolved, ethylparaben was added and stirring was continued for 5 hours, and the gel became clear and transparent after standing for 24 hours.
Example 7: anti-influenza virus activity of hydrogels containing boric acid and sodium nitrite compositions
The usage is as follows: exemplary hydrogels containing boric acid and sodium nitrite were prepared according to example 6, respectively, and mixed in a volume ratio of 1:1 to form a composition for antiviral activity testing, operating as in example 1, a:0 < Δlg <1; b is 1-delta lg <3; c is 3-delta lg <5.5; d is less than or equal to 5.5 and delta lg.
TABLE 8 anti-influenza Virus Activity of hydrogels containing boric acid and sodium nitrite compositions
As shown in Table 8, the hydrogel containing the boric acid and nitrous acid composition has remarkable anti-influenza virus activity, and its TCID is compared with that of physiological saline group 50 Drop by 10 5.5 Multiple times and above. And the hydrogel of the boric acid and sodium nitrite composition has a long-acting antiviral effect, and can be effectively inhibited after 24 hours.
Example 8: anti-herpes simplex virus activity of hydrogel containing boric acid and sodium nitrite composition
The usage is as follows: exemplary hydrogels containing boric acid and sodium nitrite were prepared separately according to example 6 and mixed in a volume ratio of 1:1 to form a composition for anti-herpes simplex virus activity testing, antiviral activity testing procedure: the sample/blank is mixed with HSV-1KOS virus strain suspension with a titer of 1 x 10e≡8/mL in a volume ratio of 20:3, incubated at 25 ℃ for 20min, and then added with suspension (1:10) for dilution. The samples were diluted in gradient with DMEM high sugar medium, the supernatant from the well plate was aspirated, 200uL of the diluted virus solution was added to a twenty-four well plate plated with Vero cells, each dilution was repeated two times, 37℃and 5% CO 2 Culturing for 1h, shaking every 15min to make virus be adsorbed on Vero cell uniformly; after 1h of incubation, 1mL of DMEM methylcellulose broth was added to twenty-four well plates and incubation was continued for three days, and plaques produced by virus erosion of cells in the well plates were observed and counted.
TABLE 9 anti-herpes simplex Virus Activity of hydrogels containing boric acid and sodium nitrite compositions
The results are shown in Table 9, in which the hydrogels containing boric acid and nitrous acid compositions have significant anti-herpes simplex virus activity compared to the saline group. And the hydrogel of the boric acid and sodium nitrite composition has a long-acting antiviral effect, and can be effectively inhibited after 4 hours.
Example 9: preparation of emulsion containing boric acid and sodium nitrite composition
The preparation process comprises the following steps: according to the proportions of Table 10, the aqueous phase and the oil phase were heated to 65℃respectively, the oil phase was slowly added to the aqueous phase while stirring, and the mixture was completely emulsified and cooled to room temperature.
TABLE 10 exemplary emulsion BA-07 containing boric acid
The preparation process comprises the following steps: according to the proportions of Table 11, the aqueous phase and the oil phase were heated to 65℃respectively, the oil phase was slowly added to the aqueous phase while stirring, and the mixture was completely emulsified and cooled to room temperature.
TABLE 11 exemplary emulsion NA-07 containing sodium nitrite
Example 10: antibacterial Activity of compositions containing boric acid and sodium nitrite
The usage is as follows: an exemplary emulsion containing boric acid and sodium nitrite was prepared separately according to example 9 and mixed in a volume ratio of 1:1 to form a composition for antimicrobial activity testing, the antimicrobial activity testing procedure being described in reference to example 4.
TABLE 12 antibacterial Activity of aqueous solutions containing boric acid and sodium nitrite compositions
The results are shown in Table 12, where the emulsion containing the boric and nitrous acid compositions had significant activity against E.coli, staphylococcus aureus and Candida albicans.

Claims (15)

1. The composition containing boric acid and nitrite is characterized by comprising a first component and a second component, wherein the first component of the composition contains 0.5-4.0 w% of boric acid, the second component contains 0.4-4.0 w% of nitrite, the first component and the second component are respectively added into excipients to form 100%, and the first component and the second component are mixed according to a ratio of 1:1.
2. The composition of claim 1, wherein the nitrite is one or more of sodium nitrite and potassium nitrite.
3. The composition of claim 1, wherein boric acid is 6.0w% in the first component of the composition and nitrite is 3.0w% in the second component.
4. The composition of claim 1, wherein boric acid is 4.0w% in the first component and nitrite is 0.9w% in the second component of the composition.
5. The composition of claim 1, wherein boric acid is 3.0w% in the first component of the composition and nitrite is 6.0w% in the second component.
6. The composition of claim 1, wherein boric acid is 3.0w% in the first component of the composition and nitrite is 4.0w% in the second component.
7. The composition of claim 1, wherein boric acid is 2.0w% in the first component of the composition and nitrite is 1.0w% in the second component.
8. The composition of claim 1, wherein the excipient comprises one or more of solvents, diluents, wetting agents, antioxidants, chelating agents, emulsifiers, preservatives, antibacterial agents, opacifiers, colorants, gelling agents, flavoring agents, pH adjusters, thickening agents, and other suitable oily and aqueous substances.
9. The composition of claim 8, wherein the thickener is present in the composition in an amount of 0.3 to 0.6% by weight of the composition; the thickener is one or more of polyacrylic acid polymer, cellulose ether, copolymer of methyl vinyl ether and maleic anhydride, carbomer or gum, wherein the polyacrylic acid polymer is polyacrylic acid and polyacrylate polymer, the cellulose ether is hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, methyl cellulose, carboxymethyl cellulose or carboxymethyl cellulose sodium salt, and the gum is sodium alginate, xanthan gum or chitosan.
10. The composition of claim 8, wherein the humectant is present in the composition in an amount of from 10% to 30% by weight of the composition, the humectant being one or more of glycerin or propylene glycol.
11. The composition of claim 8, wherein the preservative is present in the composition in an amount of 0.1% by weight of the composition, and wherein the preservative is one or more of sorbic acid, benzoic acid, or ethylparaben.
12. The composition of claim 9, wherein the pH adjuster is present in the composition in an amount of 0.12 to 0.9w% of the first component, and wherein the pH adjuster is selected from one or more of sodium dihydrogen phosphate, ascorbic acid, salicylic acid, malic acid, lactic acid, citric acid, tartaric acid, and buffer salts.
13. The composition of claim 9, wherein the solvent is present in the composition in an amount greater than 50% by weight of the composition, and the solvent is one or more of physiological saline, sterile water.
14. Use of a composition according to claim 1 for the preparation of a medicament for external use for the treatment and/or prophylaxis of viral, bacterial and/or fungal infections, including infections caused by herpes simplex virus, staphylococcus aureus, escherichia coli, candida albicans, trichophyton rubrum or any combination thereof.
15. The use according to claim 14, wherein the topical medicament is in the form of a preparation comprising an aqueous solution, a cream, an ointment, an emulsion, a gel, a topical liquid, a paste, a wipe, a topical powder, an aerosol or a percutaneous absorbent.
CN202310588696.3A 2022-09-26 2022-09-26 Anti-pathogenic microorganism composition containing boric acid and nitrite and application thereof Pending CN116617254A (en)

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