Bacteriostatic compositions, methods of making and use thereof

Abstract

Disclosed is a bacteriostatic composition, a method for preparing the same, and use thereof. The bacteriostatic composition of the present invention comprises one or more fatty acids and / or salts thereof, one or more dibasic acids and / or salts thereof, one or more aromatic alcohols, and one or more aromatic acids and / or salts thereof. The bacteriostatic composition can be prepared as an aqueous solution, a water-soluble gel, a foam, a spray, an ointment, a powder, a film, a capsule, a suppository, or a tablet, and can be used to inhibit harmful microorganisms, particularly abnormal flora in the vagina.

Description

TECHNICAL FIELD

[0001] The present application relates to a bacteriostatic composition, to a method for inhibiting harmful microorganisms, to a method for regulating vaginal flora, to the use of fatty acids and / or salts thereof for the preparation of a bacteriostatic composition for regulating vaginal flora, and to a method for preparing a bacteriostatic composition. BACKGROUND

[0002] Human skin and mucosal sites are in communication with the outside world, are prone to be contaminated by various pathogenic bacteria, and can further develop into pathogenic bacteria colonization, infection, or carry and spread pathogenic bacteria at the skin and / or mucosal sites. Cleaning the skin and / or mucosal sites with bacteriostatic products can effectively reduce the pathogenic bacterial load at the skin and / or mucosal sites, and even kill the pathogenic bacteria, thereby helping to prevent pathogenic bacterial infection and transmission.

[0003] Various personal care products, such as skin care products, or cosmetic products, or bath products, or hair washing products, etc., and various products for medical use, pharmaceuticals, etc., need to inhibit the growth of microorganisms, and even kill the contaminating microorganisms, such as inhibiting or killing mold, yeast, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, etc., in order to prevent deterioration due to microbial contamination during storage and use.

[0004] Especially on the surface of human vaginal mucosa, there are a large number of microorganisms such as bacteria and fungi. Under healthy conditions, the bacteria in the female vagina are mainly lactobacilli, which metabolize glycogen in vaginal mucosal epithelial cells to produce acid, keeping the pH value of the vagina in the range of 3.5-4.5, and producing hydrogen peroxide, bacteriocin and other substances, which have inhibitory effect on pathogenic bacteria and opportunistic pathogens, and thus are beneficial bacteria in the vagina, or called "normal vaginal flora".

[0005] There are also Gardnerella vaginalis, Prevotella, Mobiluncus, Escherichia coli, Staphylococcus, Candida albicans, etc. in the vagina, which are not pathogenic when the number is small, but can produce harmful metabolites, toxins and other substances when the number is large, leading to pathological changes and diseases in the human body, and thus are called "opportunistic pathogens". Among Staphylococcus, Staphylococcus aureus is the most representative with strong pathogenicity; among Candida albicans, Candida albicans is the most representative, accounting for more than 70% of the total number of vaginal and / or vulvar Candida albicans infections.

[0006] When the vaginal flora is abnormal and the number of lactobacilli is small, not only the number of opportunistic pathogens such as Gardnerella vaginalis increases, but also the resistance to pathogenic bacteria with strong virulence and pathogenicity decreases, thus increasing the risk of sexually transmitted diseases, such as gonococcal, trichomonas, chlamydia, mycoplasma, HIV, HPV, etc.

[0007] The treatment of vaginal microbial diseases is currently still mainly antibacterial. Although antibacterial treatment can inhibit or kill pathogenic bacteria, it often also has inhibitory or even killing effect on beneficial lactobacilli, resulting in decreased vaginal anti-infective ability, repeated vaginal infection, or persistent infection. How to protect beneficial bacteria in the vagina during antibacterial treatment, thereby improving the prevention and treatment effect of vaginal infection, is still a hot issue in medical research.

[0008] Thus, a safe and effective bacteriostatic product is suitable for cleaning and hygiene bacteriostasis of human skin and mucosa, for preservation of personal washing and care products such as bath products, skin care products, and cosmetics, for preservation of products for medical use and pharmaceuticals, and for inhibiting abnormal vaginal flora, restoring and / or maintaining vaginal lactobacilli, restoring and / or maintaining normal vaginal flora, and restoring and / or maintaining normal vaginal microecology, thus having strong practicability and great market demand.

[0009] The information in the background art is merely intended to explain the general background of the application and should not be considered as admitting or in any form suggesting that these information constitutes prior art commonly known by those skilled in the art. SUMMARY

[0010] An object of the present application is to provide a bacteriostatic composition.

[0011] Another object of the present application is to provide a method for inhibiting harmful microorganisms.

[0012] Still another object of the present application is to provide a method for regulating vaginal flora, including inhibiting abnormal vaginal flora and restoring and / or maintaining vaginal lactobacilli.

[0013] Still another object of the present application is to provide use of fatty acids and / or salts thereof in the preparation of a bacteriostatic composition for regulating vaginal flora.

[0014] Still another object of the present application is to provide a method for preparing a bacteriostatic composition.

[0015] The present application provides a bacteriostatic composition, which comprises the following components:

[0016] (1) one or more fatty acids and / or salts thereof, the fatty acid being selected from the group consisting of acetic acid, glycolic acid, lactic acid, propionic acid, levulinic acid, butyric acid, isobutyric acid, hydroxybutyric acid, valeric acid, caproic acid, heptanoic acid, caprylic acid, pelargonic acid, capric acid, undecanoic acid, undecylenic acid, and lauric acid, preferably from the group consisting of propionic acid, butyric acid, caproic acid, caprylic acid, capric acid, and undecanoic acid, the total content of component (1) being in the range of 0.001-3.00% (w / w) based on the fatty acid;

[0017] (2) one or more dibasic acids selected from the group consisting of glutaric acid, adipic acid, and pimelic acid, and / or salts thereof, preferably the dibasic acid is adipic acid, the total content of component (2) in terms of dibasic acid is in the range of 0.05-5.00% (w / w);

[0018] (3) one or more aromatic alcohols selected from the group consisting of benzyl alcohol, 2,4-dichlorobenzyl alcohol, phenethyl alcohol, phenoxyethyl alcohol, and cinnamyl alcohol, preferably the group consisting of phenethyl alcohol and cinnamyl alcohol, the total content of component (3) is in the range of 0.03-1.00% (w / w);

[0019] (4) one or more aromatic acids selected from the group consisting of benzoic acid, p-hydroxybenzoic acid, p-methoxybenzoic acid, salicylic acid, cinnamic acid, gentisic acid, and caffeylic acid, and / or salts thereof, preferably the group consisting of benzoic acid, cinnamic acid, and p-hydroxybenzoic acid, the total content of component (4) in terms of aromatic acid is in the range of 0.03-1.00% (w / w);

[0020] The bacteriostatic composition is in one of the following dosage forms: aqueous solution, water-soluble gel, foam, spray, ointment, powder, film, capsule, suppository, and tablet, preferably aqueous solution, water-soluble gel, foam, spray, and ointment.

[0021] In some embodiments, the total content of one or more fatty acids and / or salts thereof is preferably in the range of 0.001-2.00% (w / w), more preferably in the range of 0.001-1.50% (w / w), most preferably in the range of 0.002%-1.25% (w / w) in terms of fatty acid; and / or the total content of one or more dibasic acids and / or salts thereof is preferably in the range of 0.10-3.50% (w / w), more preferably in the range of 0.50-2.50% (w / w), most preferably in the range of 0.50-1.50% (w / w) in terms of dibasic acid; and / or the total content of one or more aromatic alcohols is preferably in the range of 0.03-0.70% (w / w), more preferably in the range of 0.05-0.60% (w / w), most preferably in the range of 0.08-0.50% (w / w); and / or the total content of one or more aromatic acids and / or salts thereof is preferably in the range of 0.03-0.50% (w / w), more preferably in the range of 0.05-0.25% (w / w), most preferably in the range of 0.08-0.20% (w / w) in terms of aromatic acid.

[0022] In some embodiments, the bacteriostatic composition further contains one or more dibasic and / or polybasic acids selected from the group consisting of malic acid, citric acid, succinic acid, tartaric acid, maleic acid, isocitric acid, suberic acid, azelaic acid, and sebacic acid, and / or salts thereof, in a total amount ranging from 0.10 to 2.50% (w / w), preferably one or more dibasic and / or polybasic acids selected from the group consisting of malic acid, citric acid, and succinic acid, and / or salts thereof. The acids and / or salts thereof have a buffering effect, which can enhance the pH stability of the bacteriostatic composition of the present disclosure, and further enhance the pH adjustment effect of the bacteriostatic composition of the present disclosure on the skin and / or mucosal sites of the human body.

[0023] In some embodiments, the bacteriostatic composition optionally contains one or more monosaccharides and / or oligosaccharides and / or polysaccharides selected from the group consisting of glucose, fructose, mannose, galactose, maltose, isomaltose, sucrose, isomaltulose, lactose, lactulose, trehalose, cellobiose, melibiose, gentiobiose, raffinose, stachyose, melezitose, isomaltotriose, isomaltotetraose, isomaltopentaose, low maltose, raffinose, panose, isomaltulose oligomers, fructooligosaccharides, glucomannan, galactooligosaccharides, dextrin, starch, and glycogen, in a total amount ranging from 0.01 to 20.00% (w / w), preferably isomaltulose, lactose, lactulose, maltose, isomaltose, trehalose, glycogen, or a mixture thereof in a total amount ranging from 0.10 to 2.00% (w / w). The sugar-containing bacteriostatic composition of the present disclosure can not only inhibit Candida, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Gardnerella vaginalis, Prevotella, Mobiluncus, Aspergillus niger, and abnormal flora at the skin and / or mucosal sites, but also promote and / or maintain lactic acid bacteria at the skin and / or mucosal sites, promote and / or maintain the acidity at the skin and / or mucosal sites, and can be used for preventing and / or treating the decrease of lactic acid bacteria at the skin and / or mucosal sites, the dysbiosis of the flora at the skin and / or mucosal sites, such as for preventing and / or treating bacterial vaginosis, or aerobic vaginitis, or atrophic vaginitis, or for adjuvant therapy of vaginitis, or for recovery after vaginitis treatment, or for the treatment of infections of the genital tract, and the like.

[0024] In some embodiments, the bacteriostatic composition optionally contains one or more amino acids and / or salts thereof selected from the group consisting of L-glutamic acid, glutamine, L-aspartic acid, asparagine, leucine, isoleucine, phenylalanine, valine, proline, and threonine, in a total amount ranging from 0.10 to 6.00% (w / w), preferably glutamic acid and / or salts thereof and / or aspartic acid and / or salts thereof, or mixtures thereof, in a total amount ranging from 0.50 to 3.00% (w / w). The bacteriostatic composition containing amino acids and / or salts thereof of the present disclosure can reduce the acid production of lactic acid bacteria, thereby reducing the acidity of the skin and / or mucosal sites, and is suitable for adjusting the microenvironment of the skin and / or mucosal sites, such as for treating or assisting in the treatment of cytolytic vaginosis, vulvovaginal candidiasis, and the like.

[0025] In some embodiments, the bacteriostatic composition optionally contains one or more monoterpenes or sesquiterpenes, including but not limited to citronellol, linalool, geraniol, nerol, eucalyptol, terpinen-4-ol, carvesol, menthol, and lavandulol, in a total amount ranging from 0.001 to 0.50% (w / w). The monoterpenes or sesquiterpenes can not only enhance the bacteriostatic effect of the composition, but also provide a fragrant odor to the composition.

[0026] In some embodiments, the bacteriostatic composition optionally contains one or more plant fragrant oils, including but not limited to rose essential oil, clove oil, musk oil, lavender oil, mint oil, wormwood leaf oil, eucalyptus oil, camphor oil, Chinese bayberry essential oil, cinnamon essential oil, bay leaf oil, and thyme oil, in a total amount ranging from 0.0001 to 0.05% (w / w). The plant fragrant oils can not only enhance the bacteriostatic effect of the composition, but also provide a fragrant odor to the composition.

[0027] In some embodiments, the bacteriostatic composition optionally contains one or more vitamin substances selected from the group consisting of vitamin A, vitamin C, vitamin D, and vitamin E, in a total amount ranging from 0.001 to 0.50% (w / w), which can be high-purity vitamin substances or plant extracts containing the vitamin substances. The vitamin substances have the effects of antioxidation, promoting skin cell growth, regulating immune function, maintaining the integrity of mucosal epithelial cells, and the like, can enhance the stability of the bacteriostatic composition, or have a protective effect on the human skin and / or mucosa.

[0028] In some embodiments, the bacteriostatic composition optionally comprises one or more components selected from the group consisting of dehydroacetic acid, sodium dehydroacetate, sorbic acid, potassium sorbate, sodium sorbate, natamycin, everninic acid, ambrettolide, cinnamaldehyde, adonitol, chlorogenic acid, 1,2-pentanediol, 1,2-hexanediol, 1,6-hexanediol, 1,2-octanediol, 1,2-decanediol, p-acetolactone, 2,4-dihydroxyacetophenone, methyl paraben, ethyl paraben, propyl paraben, lysozyme, glycerol monocaprylate, glycerol monocaprate, and glycerol monolaurate. The components are used to further enhance the bacteriostatic effect of the bacteriostatic composition of the present disclosure on Candida spp., Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Gardnerella vaginalis, Prevotella spp., Mobiluncus spp., Aspergillus niger, abnormal flora at skin and / or mucosal sites, and other harmful microorganisms including, but not limited to, viruses such as HIV, HPV, and the like.

[0029] In some embodiments, the bacteriostatic composition further comprises one or more antibacterial drugs including, but not limited to, nitroimidazoles such as metronidazole, tinidazole, ornidazole, aminoglycosides such as gentamicin, tobramycin, amikacin, sisomicin, netilmicin, quinolones such as ciprofloxacin, ofloxacin, levofloxacin, furans such as nifuratel, nifursemux, furacillin, furazolidone, nitrofurantoin, sulfonamides such as silver sulfadiazine, sodium sulfacetamide, azoles such as clotrimazole, fluconazole, miconazole, ketoconazole, propenamides such as naftifine, terbinafine, polyenes such as amphotericin B, nystatin, candidin, natamycin. Preferably, metronidazole, nifuratel, clotrimazole, or a mixture thereof. The bacteriostatic composition of the present disclosure comprising an antibacterial drug is suitable for use on skin and / or mucosa, such as for preventing and / or treating bacterial and / or fungal infections of the skin, for preventing and / or treating bacterial or fungal infections of the oral mucosa, and for preventing and / or treating bacterial vaginosis, or aerobic vaginitis, or vulvovaginal candidiasis of the vaginal mucosa, and the like.

[0030] In some embodiments, the bacteriostatic composition is in one of the following dosage forms: an aqueous solution, a water-soluble gel, a foam, a spray, and an ointment; the aqueous solution, or the water-soluble gel, or the foam, or the spray, or the ointment has a pH in the range of 3.1-4.8, preferably a pH in the range of 3.6-4.6, more preferably a pH in the range of 3.8-4.4.

[0031] In some embodiments, the bacteriostatic composition is a water-soluble gel further comprising one or more non-flowing, viscous, water-soluble colloidal bases including, but not limited to, xanthan gum, carbomer, polycarbophil, dextran, glucomannan, tragacanth gum, gum acacia, methylcellulose (MC), carboxymethylcellulose (CMC), hydroxyethylcellulose (HEC), hydroxyethylmethylcellulose (HEMC), hydroxypropylmethylcellulose (HPMC), preferably xanthan gum, carbomer.

[0032] The bacteriostatic composition of the present disclosure has inhibitory effect on harmful microorganisms, including but not limited to Candida albicans, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Gardnerella vaginalis, Prevotella, Mobiluncus, Aspergillus niger, abnormal flora of skin and / or mucosa, other various pathogenic or conditionally pathogenic aerobic bacteria, facultative anaerobic bacteria, anaerobic bacteria, molds, and viruses such as HPV, HIV, and the like.

[0033] Thus, the bacteriostatic composition of the present disclosure can be used for cleaning and / or bacteriostasis and / or disinfection of human skin and / or mucosa, such as cleaning and / or bacteriostasis and / or disinfection of vaginal mucosa, and can also be used for the preservation of various bath products, hair washing products, skin care products, cosmetics, and other personal care products, or for the preservation of products for medical use, pharmaceutical products, and the like.

[0034] In some embodiments, the bacteriostatic composition of the present disclosure can be used as a therapeutic product, or an effective component thereof, or a preservative thereof, including but not limited to pharmaceutical products, disinfectants, mucosal surface microbicides, antibacterial agents, bacteriostatic agents, microecological modulators, flora modulators, microenvironment modulators, microbial modulators, single-use medical products, and the like, or in the form of a component of medical devices, pharmaceutical devices, disinfecting devices, and vaginal devices.

[0035] In some embodiments, the bacteriostatic composition of the present disclosure is a non-therapeutic product, or an effective component thereof, or a preservative thereof, wherein the non-therapeutic product is in the form of one of the following groups: health care products, hygiene products, personal care products, cosmetics, single-use hygiene products, cleaning products, daily use products, microecological care products, odor-removing agents, lubricants, moisturizers, lotions, detergents, maintenance agents, anti-itching agents, fresheners, or in the form of a component of sanitary napkins, sanitary pads, and sanitary tampons.

[0036] In some embodiments, the bacteriostatic composition of the present disclosure is a vaginal bacteriostatic composition comprising the following components:

[0037] (1) one or more fatty acids and / or salts thereof selected from the group consisting of acetic acid, hydroxyacetic acid, lactic acid, propionic acid, levulinic acid, butyric acid, valeric acid, caproic acid, heptanoic acid, caprylic acid, pelargonic acid, capric acid, undecanoic acid, undecylenic acid, and lauric acid, in a total amount ranging from 0.001 to 2.00% (w / w), preferably propionic acid, butyric acid, caproic acid, caprylic acid, capric acid, undecanoic acid, or a mixture thereof in a total amount ranging from 0.001 to 1.50% (w / w), more preferably in a total amount ranging from 0.002 to 1.25% (w / w);

[0038] (2) one or more dibasic acids and / or salts thereof selected from the group consisting of glutaric acid, adipic acid, pimelic acid, in a total amount ranging from 0.50 to 2.50% (w / w), preferably adipic acid in a total amount ranging from 0.50 to 1.50% (w / w);

[0039] (3) one or more aromatic alcohols selected from the group consisting of benzyl alcohol, 2,4-dichlorobenzyl alcohol, phenethyl alcohol, phenoxyethyl alcohol, cinnamic alcohol, in a total amount ranging from 0.05 to 0.60% (w / w), preferably phenethyl alcohol, cinnamic alcohol, or a mixture thereof in a total amount ranging from 0.08 to 0.50% (w / w);

[0040] (4) one or more aromatic acids and / or salts thereof selected from the group consisting of benzoic acid, p-hydroxybenzoic acid, p-methoxybenzoic acid, salicylic acid, cinnamic acid, gentisic acid, and caffeic acid, in a total amount ranging from 0.05 to 0.25% (w / w), preferably benzoic acid, cinnamic acid, p-hydroxybenzoic acid, or a mixture thereof in a total amount ranging from 0.08 to 0.20% (w / w).

[0041] The vaginal bacteriostatic composition of the present disclosure adopts one of the following dosage forms: aqueous solution, water-soluble gel, foam, spray, ointment, powder, film, capsule, suppository, and tablet, preferably aqueous solution, water-soluble gel, foam, spray, and ointment.

[0042] In some embodiments, the vaginal bacteriostatic composition of the present disclosure further contains one or more estrogenic substances selected from the group consisting of stilbestrol, hexestrol, estradiol, estrone, estriol, nylestriol, ethinyl estradiol, ethinyl estradiol cypionate, quinestrol, and proligestone, in a total amount ranging from 0.001 to 1.00% (w / w), preferably estriol and proligestone. The vaginal bacteriostatic composition of the present disclosure containing estrogenic substances can promote the synthesis of glycogen by vaginal mucosal epithelial cells and promote the growth of beneficial lactobacilli, and is particularly suitable for use during or after menopause or postpartum.

[0043] In some embodiments, the bacteriostatic composition for vagina of the present disclosure further contains one or more phytoestrogens selected from the group consisting of daidzin, daidzein, glycitein, puerarin, coumestrol, genistein, equol, apigenin, genistin, genistein, biochanin A, formononetin, formononetin, resveratrol, secoisolaricirecinol, and lignan, in a total amount ranging from 0.001 to 1.00% (w / w). The bacteriostatic composition for vagina of the present disclosure containing phytoestrogens can promote the synthesis of glycogen by vaginal mucosal epithelial cells, promote the growth of beneficial lactobacilli, and is particularly suitable for use in menopausal or postmenopausal or postpartum women.

[0044] The bacteriostatic composition for vagina of the present disclosure can optionally contain different dosage form bases such as water or xanthan gum or carbomer, or further contain one or more components as described above, such as dibasic acid and / or salt thereof, polybasic acid and / or salt thereof, and / or antibacterial agent, and / or sugar substance, and / or amino acid substance, and / or monoterpenes or sesquiterpenes, and / or plant aromatic oil substance, and / or vitamin, and / or antibacterial drug substance, in a total amount ranging from 0.10 to 2.50% (w / w), 0.01 to 20.00%, 0.10 to 6.00% (w / w), 0.001 to 0.50% (w / w), 0.0001 to 0.05% (w / w), 0.001 to 0.50% (w / w), and 0.001 to 0.50% (w / w), respectively.

[0045] The bacteriostatic composition for vagina of the present disclosure has inhibitory effect on abnormal flora in the vagina, but has restoring and / or maintaining and / or promoting effect on lactobacilli in the vagina, and can be used to restore and / or maintain normal flora in the vagina, restore and / or maintain normal microecology in the vagina, and restore and / or maintain normal acidity in the vagina.

[0046] Thus, the bacteriostatic composition for vagina of the present disclosure can be used for cleaning and caring for the vagina and / or vulva, and / or relieving and / or eliminating itching, and / or pain, and / or dryness, and / or irritation, and / or sexual discomfort of the vagina and / or vulva, and / or relieving and / or eliminating abnormal discharge, and / or abnormal odor of the discharge, and the like, and for preventing and / or treating and / or assisting in the treatment of vaginal flora disorder, and / or bacterial vaginosis, and / or aerobic vaginitis, and / or cytolytic vaginosis, and / or vulvovaginal candidiasis, and / or atrophic vaginitis, and the like.

[0047] The present application also provides a method of inhibiting harmful microorganisms comprising the step of using the bacteriostatic composition, wherein the bacteriostatic composition comprises:

[0048] (1) one or more fatty acids selected from the group consisting of acetic acid, glycolic acid, lactic acid, propionic acid, levulinic acid, butyric acid, isobutyric acid, hydroxybutyric acid, valeric acid, caproic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, undecylenic acid, and lauric acid, preferably from the group consisting of propionic acid, butyric acid, caproic acid, octanoic acid, decanoic acid, and undecanoic acid; the total content of component (1) is in the range of 0.001-3.00% (w / w), preferably in the range of 0.001-2.00% (w / w), more preferably in the range of 0.001-1.50% (w / w), most preferably in the range of 0.002%-1.25% (w / w) based on the fatty acid;

[0049] (2) one or more dibasic acids selected from the group consisting of glutaric acid, adipic acid, and pimelic acid, preferably adipic acid; the total content of component (2) is in the range of 0.05-5.00% (w / w), preferably in the range of 0.10-3.50% (w / w), more preferably in the range of 0.50-2.50% (w / w), most preferably in the range of 0.50-1.50% (w / w) based on the dibasic acid;

[0050] (3) one or more aromatic alcohols selected from the group consisting of benzyl alcohol, 2,4-dichlorobenzyl alcohol, phenethyl alcohol, phenoxyethyl alcohol, and cinnamyl alcohol, preferably phenethyl alcohol, cinnamyl alcohol, or a mixture thereof; the total content of component (3) is in the range of 0.03-1.00% (w / w), preferably in the range of 0.03-0.70% (w / w), more preferably in the range of 0.05-0.60% (w / w), most preferably in the range of 0.08-0.50% (w / w);

[0051] (4) one or more aromatic acids selected from the group consisting of benzoic acid, p-hydroxybenzoic acid, p-methoxybenzoic acid, salicylic acid, cinnamic acid, gentisic acid, and caffeylic acid, preferably from the group consisting of benzoic acid, cinnamic acid, and p-hydroxybenzoic acid; the total content of component (4) is in the range of 0.03-1.00% (w / w), preferably in the range of 0.03-0.50% (w / w), more preferably in the range of 0.05-0.25% (w / w), most preferably in the range of 0.08-0.20% (w / w) based on the aromatic acid.

[0052] The bacteriostatic composition is in one of the following dosage forms: an aqueous solution, a water-soluble gel, a foam, a spray, an ointment, a powder, a film, a capsule, a suppository, and a tablet, preferably an aqueous solution, a water-soluble gel, a foam, a spray, and an ointment.

[0053] In some embodiments, the harmful microorganism in the method for inhibiting harmful microorganism of the present disclosure includes, but is not limited to, at least one of the following microorganisms: Candida albicans, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Gardnerella vaginalis, Prevotella, Mobiluncus, Aspergillus niger, abnormal flora of skin and / or mucous membrane, other various pathogenic or conditionally pathogenic aerobic bacteria, facultative anaerobic bacteria, anaerobic bacteria, molds, and viruses HPV, HIV, etc.

[0054] Thus, the bacteriostatic composition in the method for inhibiting harmful microorganism of the present disclosure can be used for cleaning and / or bacteriostasis and / or disinfection of human skin and / or mucous membrane, such as cleaning and / or bacteriostasis and / or disinfection of vaginal mucous membrane, and can also be used for the preservation of various bath products, or shampoo products, or skin care products, or cosmetic products, and other personal care products, or for the preservation of products for medical use, pharmaceutical products, etc.

[0055] In some embodiments, the bacteriostatic composition in the method for inhibiting harmful microorganism of the present disclosure is a therapeutic product, or an effective component thereof, or a preservative thereof, which includes, but is not limited to, pharmaceutical products, disinfectants, antibacterial agents, bacteriostatic agents, mucous membrane surface microbicides, flora modulators, microecological modulators, microenvironment modulators, microbial modulators, single-use medical products, etc., or is a component of medical devices, pharmaceutical devices, disinfection devices, and vaginal devices.

[0056] In some embodiments, the bacteriostatic composition in the method for inhibiting harmful microorganism of the present disclosure is a non-therapeutic product, or an effective component thereof, or a preservative thereof, which includes, but is not limited to, health care products, personal care products, cosmetic products, sanitary products, disposable sanitary products, cleaning products, daily necessities, microecological care products, odor-removing agents, lubricants, moisturizers, lotions, detergents, maintenance agents, anti-itching agents, fresheners, etc., or can be a component of sanitary products or cleaning care products, such as a component of sanitary napkins, sanitary pads, or sanitary tampons.

[0057] When the bacteriostatic composition described in the method for inhibiting harmful microorganisms of the present disclosure is used for preservation, the content of each component of the bacteriostatic composition described in the present disclosure, i.e., the total content of one or more fatty acids and / or salts thereof calculated as fatty acid, the total content of one or more dibasic acids and / or salts thereof calculated as dibasic acid, the total content of one or more aromatic alcohols, the total content of one or more aromatic acids and / or salts thereof calculated as aromatic acid, etc., contained in a product such as a bath product, or a shampoo product, or a skin care product, or a cosmetic product, or a pharmaceutical product, and other medical use products, etc., must be within the range of the total content of the four components of the bacteriostatic composition described in the present disclosure.

[0058] The present disclosure also provides a method for regulating vaginal flora, wherein regulating vaginal flora comprises at least one of inhibiting abnormal vaginal flora, restoring and / or maintaining lactobacilli in the vagina, the method comprising the step of using a vaginal bacteriostatic composition, wherein the vaginal bacteriostatic composition contains one or more fatty acids and / or salts thereof in a total content ranging from 0.001 to 2.00% (w / w) calculated as fatty acid, the fatty acid being selected from the group consisting of butyric acid, valeric acid, caproic acid, heptanoic acid, caprylic acid, pelargonic acid, capric acid, undecanoic acid, undecylenic acid, and lauric acid, preferably a fatty acid selected from the group consisting of butyric acid, caproic acid, caprylic acid, capric acid, undecanoic acid, or a mixture thereof in a total content ranging from 0.001 to 1.50% (w / w), more preferably from 0.002 to 1.25% (w / w), and / or salts thereof.

[0059] The vaginal bacteriostatic composition described in the method for regulating vaginal flora of the present disclosure can be in any one of the following dosage forms: an aqueous solution, a water-soluble gel, a foam, a spray, an ointment, a powder, a film, a capsule, a suppository, and a tablet; preferably an aqueous solution, a water-soluble gel, a foam, a spray, and an ointment.

[0060] In some embodiments, the vaginal bacteriostatic composition described in the method for regulating vaginal flora of the present disclosure further contains one or more dibasic acids and / or salts thereof in a total content ranging from 0.50 to 2.50% (w / w) calculated as dibasic acid, the dibasic acid being selected from the group consisting of glutaric acid, adipic acid, and pimelic acid, preferably adipic acid and / or salts thereof in a total content ranging from 0.50 to 1.50% (w / w). The combination of adipic acid and / or salts thereof and the fatty acid and / or salts thereof of the present disclosure, such as butyric acid, can enhance the bacteriostatic effect of the fatty acid and / or salts thereof on Candida albicans.

[0061] In some embodiments, the bacteriostatic composition for vagina used in the method of modulating vaginal flora of the present application further contains one or more aromatic alcohols selected from the group consisting of benzyl alcohol, 2,4-dichlorobenzyl alcohol, phenyl ethyl alcohol, phenoxy ethyl alcohol, cinnamyl alcohol, preferably phenyl ethyl alcohol, cinnamyl alcohol, or a mixture thereof, in a total content ranging from 0.05 to 0.60% (w / w). The aromatic alcohols such as phenyl ethyl alcohol in combination with the fatty acids such as butyric acid and / or salts thereof of the present disclosure can enhance the bacteriostatic effect of the fatty acids and / or salts thereof on Candida albicans, Staphylococcus aureus, Escherichia coli, and abnormal vaginal flora, etc.

[0062] In some embodiments, the bacteriostatic composition for vagina used in the method of modulating vaginal flora of the present application further contains one or more aromatic acids and / or salts thereof in a total content ranging from 0.05 to 0.25% (w / w) as aromatic acid, the aromatic acid being selected from the group consisting of benzoic acid, p-hydroxybenzoic acid, p-methoxybenzoic acid, salicylic acid, cinnamic acid, gentisic acid, and coffee acid, preferably benzoic acid, cinnamic acid, p-hydroxybenzoic acid, or a mixture thereof in a total content ranging from 0.08 to 0.20% (w / w). The aromatic acids such as benzoic acid and / or salts thereof in combination with the fatty acids such as butyric acid and / or salts thereof of the present disclosure can enhance the bacteriostatic effect of the fatty acids and / or salts thereof on Candida albicans, Staphylococcus aureus, Escherichia coli, and abnormal vaginal flora, etc.

[0063] In some embodiments, the bacteriostatic composition for vagina used in the method of modulating vaginal flora of the present application contains: (1) one or more fatty acids and / or salts thereof in a total content ranging from 0.001 to 2.00% (w / w) as fatty acid, the fatty acid being selected from the group consisting of butyric acid, valeric acid, caproic acid, heptanoic acid, caprylic acid, nonanoic acid, capric acid, undecanoic acid, undecylenic acid, and lauric acid, preferably a fatty acid selected from the group consisting of butyric acid, caproic acid, caprylic acid, capric acid, undecanoic acid, or a mixture thereof in a total content ranging from 0.001 to 1.50% (w / w), more preferably from 0.002 to 1.25% (w / w), and / or salts thereof; (2) one or more dibasic acids and / or salts thereof in a total content ranging from 0.50 to 2.50% (w / w) as dibasic acid, the dibasic acid being selected from the group consisting of glutaric acid, adipic acid, and pimelic acid, preferably adipic acid in a total content ranging from 0.50 to 1.50% (w / w), and / or salts thereof; (3) one or more aromatic alcohols selected from the group consisting of benzyl alcohol, 2,4-dichlorobenzyl alcohol, phenyl ethyl alcohol, phenoxy ethyl alcohol, cinnamyl alcohol in a total content ranging from 0.05 to 0.60% (w / w), preferably phenyl ethyl alcohol, cinnamyl alcohol, or a mixture thereof in a total content ranging from 0.08 to 0.50% (w / w).

[0064] The combination of adipic acid or the like dicarboxylic acid and / or its salt, phenyl ethanol or the like aromatic alcohol, and butyric acid or the like fatty acid and / or its salt of the present disclosure has a synergistic bacteriostatic effect on Candida albicans, Staphylococcus aureus, Escherichia coli, and the like, and an inhibitory effect on abnormal vaginal flora.

[0065] In some embodiments, the bacteriostatic composition for vagina described in the method of modulating vaginal flora of the present disclosure contains: (1) one or more fatty acids and / or salts thereof in a total content ranging from 0.001 to 2.00% (w / w) based on the fatty acid, the fatty acid being selected from the group consisting of butyric acid, valeric acid, caproic acid, heptanoic acid, caprylic acid, pelargonic acid, capric acid, undecanoic acid, undecylenic acid, and lauric acid, preferably a fatty acid selected from the group consisting of butyric acid, caproic acid, caprylic acid, capric acid, undecanoic acid, or a mixture thereof in a total content ranging from 0.001 to 1.50% (w / w), more preferably ranging from 0.002 to 1.25% (w / w), and / or a salt thereof; (2) one or more dicarboxylic acids and / or salts thereof in a total content ranging from 0.50 to 2.50% (w / w) based on the dicarboxylic acid, the dicarboxylic acid being selected from the group consisting of glutaric acid, adipic acid, and pimelic acid, preferably adipic acid in a total content ranging from 0.50 to 1.50% (w / w), and / or a salt thereof; (3) one or more aromatic acids and / or salts thereof in a total content ranging from 0.05 to 0.25% (w / w) based on the aromatic acid, the aromatic acid being selected from the group consisting of benzoic acid, p-hydroxybenzoic acid, p-methoxybenzoic acid, salicylic acid, cinnamic acid, gentisic acid, and caffeic acid, preferably an aromatic acid selected from the group consisting of benzoic acid, cinnamic acid, p-hydroxybenzoic acid, or a mixture thereof in a total content ranging from 0.08 to 0.20% (w / w), and / or a salt thereof.

[0066] The combination of adipic acid or the like dicarboxylic acid and / or its salt, benzoic acid or the like aromatic acid and / or its salt, and butyric acid or the like fatty acid and / or its salt of the present disclosure has a synergistic bacteriostatic effect on Candida albicans, Staphylococcus aureus, Escherichia coli, and the like, and an inhibitory effect on abnormal vaginal flora.

[0067] In some embodiments, the bacteriostatic composition for vagina described in the method of modulating vaginal flora of the present disclosure contains: (1) one or more fatty acids and / or salts thereof in a total content ranging from 0.001 to 2.00% (w / w) as a fatty acid, the fatty acid being selected from the group consisting of butyric acid, valeric acid, caproic acid, heptanoic acid, caprylic acid, pelargonic acid, capric acid, undecanoic acid, undecylenic acid, and lauric acid, preferably a fatty acid selected from the group consisting of butyric acid, caproic acid, caprylic acid, capric acid, undecanoic acid, or a mixture thereof in a total content ranging from 0.001 to 1.50% (w / w), more preferably ranging from 0.002 to 1.25% (w / w), and / or salts thereof; (2) one or more aromatic alcohols selected from the group consisting of benzyl alcohol, 2,4-dichlorobenzyl alcohol, phenethyl alcohol, phenoxyethanol, and cinnamyl alcohol in a total content ranging from 0.05 to 0.60% (w / w), preferably phenethyl alcohol, cinnamyl alcohol, or a mixture thereof in a total content ranging from 0.08 to 0.50% (w / w); (3) one or more aromatic acids and / or salts thereof in a total content ranging from 0.05 to 0.25% (w / w) as an aromatic acid, the aromatic acid being selected from the group consisting of benzoic acid, p-hydroxybenzoic acid, p-methoxybenzoic acid, salicylic acid, cinnamic acid, gentisic acid, and caffeic acid, preferably an aromatic acid selected from the group consisting of benzoic acid, cinnamic acid, p-hydroxybenzoic acid, or a mixture thereof in a total content ranging from 0.08 to 0.20% (w / w), and / or salts thereof.

[0068] The combination of the aromatic alcohol such as phenethyl alcohol, the aromatic acid such as benzoic acid, and / or salts thereof, and the fatty acid such as butyric acid, and / or salts thereof of the present disclosure has a synergistic bacteriostatic effect on Candida albicans, Staphylococcus aureus, Escherichia coli, and the like, and an inhibitory effect on abnormal vaginal flora.

[0069] In some embodiments, the bacteriostatic composition for the vagina in the method of modulating vaginal flora of the present disclosure contains: (1) one or more fatty acids and / or salts thereof in a total amount ranging from 0.001 to 2.00% (w / w) based on the fatty acid, the fatty acid being selected from the group consisting of butyric acid, valeric acid, caproic acid, heptanoic acid, caprylic acid, pelargonic acid, capric acid, undecanoic acid, undecylenic acid, and lauric acid, preferably a fatty acid selected from the group consisting of butyric acid, caproic acid, caprylic acid, capric acid, undecanoic acid, or a mixture thereof in a total amount ranging from 0.001 to 1.50% (w / w), more preferably from 0.002 to 1.25% (w / w), and / or salts thereof; (2) one or more dibasic acids and / or salts thereof in a total amount ranging from 0.50 to 2.50% (w / w) based on the dibasic acid, the dibasic acid being selected from the group consisting of glutaric acid, adipic acid, and pimelic acid, preferably adipic acid in a total amount ranging from 0.50 to 1.50% (w / w), and / or salts thereof; (3) one or more aromatic alcohols selected from the group consisting of benzyl alcohol, 2,4-dichlorobenzyl alcohol, phenyl ethanol, phenoxy ethanol, and cinnamic alcohol in a total amount ranging from 0.05 to 0.60% (w / w), preferably phenyl ethanol, cinnamic alcohol, or a mixture thereof in a total amount ranging from 0.08 to 0.50% (w / w); (4) one or more aromatic acids and / or salts thereof in a total amount ranging from 0.05 to 0.25% (w / w) based on the aromatic acid, the aromatic acid being selected from the group consisting of benzoic acid, p-hydroxybenzoic acid, p-methoxybenzoic acid, salicylic acid, cinnamic acid, gentisic acid, and caffeic acid, preferably an aromatic acid selected from the group consisting of benzoic acid, cinnamic acid, p-hydroxybenzoic acid, or a mixture thereof in a total amount ranging from 0.08 to 0.20% (w / w), and / or salts thereof.

[0070] The combination of the dibasic acid such as adipic acid and / or salts thereof, the aromatic alcohol such as phenyl ethanol, the aromatic acid such as benzoic acid and / or salts thereof, and the fatty acid such as butyric acid and / or salts thereof of the present disclosure has a synergistic bacteriostatic effect on Candida albicans, Staphylococcus aureus, Escherichia coli, and the like, and an inhibitory effect on abnormal vaginal flora. After the application of the bacteriostatic composition to the vagina, the abnormal flora in the vagina is significantly reduced, and the Lactobacillus is significantly increased, and the composition has an effect of inhibiting abnormal vaginal flora, restoring and / or maintaining and / or promoting Lactobacillus in the vagina, and restoring and / or maintaining the normal acidity of the vagina.

[0071] In some embodiments, the bacteriostatic composition for vaginal use as described in the method of modulating vaginal flora of the present disclosure further comprises one or more estrogenic substances selected from the group consisting of diethylstilbestrol, hexestrol, estradiol, estrone, estriol, nylestriol, ethinyl estradiol, ethinyl estradiol cypionate, ethinyl estradiol valerate, progestin, and proligestril, preferably estriol, and proligestril, in a total amount ranging from 0.001 to 1.00% (w / w). Estrogenic substances can promote glycogen synthesis in vaginal mucosal epithelial cells, promote the growth of beneficial lactobacilli, and the bacteriostatic composition of the present disclosure containing estrogenic substances is particularly suitable for use during or after menopause or postpartum.

[0072] In some embodiments, the bacteriostatic composition for vaginal use as described in the method of modulating vaginal flora of the present disclosure further comprises one or more phytoestrogenic substances selected from the group consisting of daidzin, daidzein, glycitein, puerarin, coumestrol, genistein, equol, apigenin, genistin, genistin, biochanin A, formononetin, formononetin, pterostilbene, secoisolaricirecinol, and lignan, preferably in a total amount ranging from 0.001 to 1.00% (w / w). Phytoestrogenic substances can promote glycogen synthesis in vaginal mucosal epithelial cells, promote the growth of beneficial lactobacilli, and the bacteriostatic composition of the present disclosure containing phytoestrogenic substances is particularly suitable for use during or after menopause or postpartum.

[0073] In some embodiments, the method of modulating vaginal flora of the present disclosure comprises the use of a bacteriostatic composition for vaginal use for restoring and / or maintaining the normal vaginal flora, and / or restoring and / or maintaining the normal microecosystem of the vagina, and / or restoring and / or maintaining the normal acidity of the vagina, and / or for the sanitary care of the vagina and / or vulva, and / or for reducing and / or eliminating itching, and / or pain, and / or dryness, and / or irritation, and / or dyspareunia of the vulva, and / or for reducing and / or eliminating abnormal discharge, and / or abnormal odor of the discharge.

[0074] In some embodiments, the method of modulating vaginal flora of the present disclosure comprises the use of a bacteriostatic composition for vaginal use for preventing and / or treating vaginal flora dysbiosis, and / or bacterial vaginosis, and / or aerobic vaginitis, and / or cytolytic vaginosis, and / or vulvovaginal candidiasis, and / or atrophic vaginitis.

[0075] The present application also provides the use of a fatty acid and / or a salt thereof in the manufacture of an antibacterial composition for regulating vaginal flora, said fatty acid being at least one selected from the group consisting of butyric acid, valeric acid, caproic acid, heptanoic acid, caprylic acid, pelargonic acid, capric acid, undecanoic acid, undecylenic acid, and lauric acid, the total content of said fatty acid and / or a salt thereof in the composition being in the range of 0.001-2.00% (w / w) based on the fatty acid; preferably the total content is in the range of 0.001-1.50% (w / w), more preferably in the range of 0.002-1.25% (w / w) of a fatty acid and / or a salt thereof selected from the group consisting of butyric acid, caproic acid, caprylic acid, capric acid, undecanoic acid, or a mixture thereof.

[0076] In some embodiments, the use of a fatty acid and / or a salt thereof according to the present application in the manufacture of an antibacterial composition for regulating vaginal flora, wherein the fatty acid and / or a salt thereof has the same concentration or property as the fatty acid and / or a salt thereof used in the method of regulating vaginal flora in the present disclosure.

[0077] In some embodiments, the use of a fatty acid and / or a salt thereof according to the present application in the manufacture of an antibacterial composition for regulating vaginal flora, wherein the regulating vaginal flora is the same type of regulating vaginal flora as in the method of regulating vaginal flora in the present disclosure, i.e. comprising at least one of the following: inhibiting abnormal vaginal flora, restoring and / or maintaining lactobacilli in the vagina.

[0078] In some embodiments, the use of a fatty acid and / or a salt thereof according to the present application in the manufacture of an antibacterial composition for regulating vaginal flora, wherein said regulating vaginal flora comprises using the antibacterial composition for the vagina to restore and / or maintain normal vaginal flora, and / or restore and / or maintain normal microecology of the vagina, and / or restore and / or maintain normal acidity of the vagina, and / or clean and care for the vagina and / or vulva, and / or reduce and / or eliminate itching, and / or pain, and / or dryness, and / or irritation, and / or sexual discomfort of the vagina and vulva, and / or reduce and / or eliminate abnormal discharge, and / or abnormal odor of the discharge.

[0079] In some embodiments, the use of a fatty acid and / or a salt thereof according to the present application in the manufacture of an antibacterial composition for regulating vaginal flora, wherein said regulating vaginal flora comprises using the antibacterial composition for the vagina to prevent and / or treat vaginal flora imbalance, and / or bacterial vaginosis, and / or aerobic vaginitis, and / or cytolytic vaginosis, and / or vulvovaginal candidiasis, and / or atrophic vaginitis.

[0080] The present application also provides a method of preparing an antibacterial composition, said method comprising the step of adding the following components to an excipient base, wherein the excipient base is an excipient base of an aqueous solution or a water-soluble colloid or a foam or a suppository or a tablet:

[0081] (1) one or more fatty acids and / or salts thereof in a total content ranging from 0.001 to 3.00% (w / w) as fatty acid, said fatty acid being selected from the group consisting of acetic acid, glycolic acid, lactic acid, propionic acid, levulinic acid, butyric acid, isobutyric acid, hydroxybutyric acid, valeric acid, caproic acid, heptanoic acid, caprylic acid, pelargonic acid, capric acid, undecanoic acid, undecylenic acid, and lauric acid, preferably propionic acid, butyric acid, caproic acid, caprylic acid, capric acid, undecanoic acid, or mixtures thereof;

[0082] (2) one or more dibasic acids and / or salts thereof selected from the group consisting of glutaric acid, adipic acid, pimelic acid, preferably adipic acid, in a total content ranging from 0.05 to 5.00% (w / w) as dibasic acid;

[0083] (3) one or more aromatic alcohols selected from the group consisting of benzyl alcohol, 2,4-dichlorobenzyl alcohol, phenethyl alcohol, phenoxyethyl alcohol, and cinnamyl alcohol, preferably phenethyl alcohol, cinnamyl alcohol, or mixtures thereof, in a total content ranging from 0.03 to 1.00% (w / w);

[0084] (4) one or more aromatic acids and / or salts thereof selected from the group consisting of benzoic acid, p-hydroxybenzoic acid, p-methoxybenzoic acid, salicylic acid, cinnamic acid, gentisic acid, and caffeic acid, preferably benzoic acid, cinnamic acid, p-hydroxybenzoic acid, or mixtures thereof, in a total content ranging from 0.03 to 1.00% (w / w) as aromatic acid;

[0085] said composition is in one of the following dosage forms: aqueous solution, water-soluble gel, foam, spray, ointment, powder, film, capsule, suppository, and tablet, preferably aqueous solution, or water-soluble gel, or foam, or spray, or ointment.

[0086] In some embodiments, the total content of the one or more fatty acids and / or salts thereof added in the preparation method, calculated as fatty acids, is preferably in the range of 0.001-2.00% (w / w), more preferably in the range of 0.001-1.50% (w / w), most preferably in the range of 0.002%-1.25% (w / w); and / or the total content of the one or more dibasic acids and / or salts thereof added, calculated as dibasic acids, is preferably in the range of 0.10-3.50% (w / w), more preferably in the range of 0.50-2.50% (w / w), most preferably in the range of 0.50-1.50% (w / w); and / or the total content of the one or more aromatic alcohols added is preferably in the range of 0.03-0.70% (w / w), more preferably in the range of 0.05-0.60% (w / w), most preferably in the range of 0.08-0.50% (w / w); and / or the total content of the one or more aromatic acids and / or salts thereof added, calculated as aromatic acids, is preferably in the range of 0.03-0.50% (w / w), more preferably in the range of 0.05-0.25% (w / w), most preferably in the range of 0.08-0.20% (w / w).

[0087] In preparing the water-soluble gel, a non-flowing, viscous, water-soluble gel base is selected that allows uniform contact of the composition with the vaginal mucosa and a prolonged residence time to allow the composition to exert its effect. In some embodiments, the base is xanthan gum, and / or carbomer, and / or polycarbophil, and / or dextran, and / or glucomannan, and / or tragacanth, and / or gum acacia, and / or methylcellulose (MC), and / or carboxymethylcellulose (CMC), and / or hydroxyethylcellulose (HEC), and / or hydroxyethylmethylcellulose (HEMC), and / or hydroxypropylmethylcellulose (HPMC), preferably xanthan gum, carbomer.

[0088] In some embodiments, the composition can be prepared by the following process: proportionally quantifying (1) one or more fatty acids and / or salts thereof, such as propionic acid and / or sodium salt thereof, (2) one or more dibasic acids and / or salts thereof, such as adipic acid and / or salts thereof, (3) one or more aromatic alcohols, such as phenyl ethanol, (4) one or more aromatic acids and / or salts thereof, such as benzoic acid and / or sodium salt thereof, (5) one or more colloidal bases, such as xanthan gum, and other components, etc., mixing them, quantitatively adding distilled water, stirring and mixing, dissolving the components and swelling the colloidal base to form a uniform gel; adjusting the pH of the composition to the range of 3.1-4.8, preferably 3.6-4.6, more preferably 3.8-4.4, using an acid and / or a base. In some embodiments, sterilization can be further performed, which can be selected from the following processes: radiation sterilization, high temperature sterilization (e.g., using 115.6°C for 15-20 minutes; or 100°C for 30 minutes), or intermittent sterilization (e.g., first treating at 80°C for 30 minutes, then placing at 36°C for 5-10 hours, again treating at 80°C for 30 minutes, then placing at 36°C for 5-10 hours, and finally treating at 80°C for 30 minutes). Alternatively, in some embodiments, the components such as benzoic acid and / or sodium salt thereof are separately formulated into a solution, which is then filtered to remove bacteria, and then added to the sterilized water-soluble gel base.

[0089] In some embodiments, when preparing a solution, the above components other than xanthan gum can be mixed, water can be added, the components can be dissolved, and sterilization can be performed, followed by dispensing; or the components can be dissolved, filtered, and then dispensed.

[0090] In some embodiments, when preparing an emulsion-type ointment, the selection of the base and the specific preparation process can refer to methods known to those skilled in the art, such as those described in Fang Liang, ed., Pharmaceutical Sciences (see Reference 1).

[0091] In some embodiments, when preparing a tablet, the quantitatively prepared fatty acids and / or salts thereof, dibasic acids and / or salts thereof, aromatic alcohols, aromatic acids and / or salts thereof, and other components, etc., can be mixed with filling excipients, and then directly compressed to obtain a tablet, according to methods known to those skilled in the art, such as those described in Fang Liang, ed., Pharmaceutical Sciences (see Reference 2). Alternatively, lubricants such as magnesium stearate or disintegrants such as sodium carboxymethyl starch can be added, mixed, and then compressed. In some embodiments, the prepared tablets can be further dispensed in a delivery device, a sterilization device, a medical device, or a pharmaceutical device.

[0092] In some embodiments, when preparing a film, a suppository, etc., methods known to those skilled in the art, such as those described in Fang Liang, ed., Pharmaceutical Sciences (see References 3, 4), can be referred to.

[0093] In some embodiments, when a sanitary napkin, or a panty liner, or a tampon containing the bacteriostatic composition of the present disclosure is prepared, the components of the present disclosure, such as fatty acids and / or their salts, dibasic acids and / or their salts, aromatic alcohols, aromatic acids and / or their salts, and the like, for example, sodium benzoate, sodium propionate, hexanoic acid, phenethyl alcohol, adipic acid, and other components, etc., can be quantitatively weighed, appropriate excipient components are added to form a powder, or a film, or a tablet, or a capsule, and then the powder, or the film, or the tablet, or the capsule is inserted into the interior of the sanitary napkin, or the panty liner, or the tampon, etc. by a suitable method or process; or the components of the present disclosure, such as sodium propionate, hexanoic acid, phenethyl alcohol, sodium benzoate, adipic acid, and other components, etc., are attached to the inner layer material of the sanitary napkin, or the panty liner, or the tampon, etc. by a suitable process, together with appropriate excipient components.

[0094] In some embodiments, when a capsule, or a suppository, or a tablet, and the like, dosage form is prepared, each component of the composition of the present disclosure is contained in a specific content range per unit dosage form. For example, one or more fatty acids and / or their salts in a total amount of 0.00005-0.15 grams as fatty acids, one or more dibasic acids and / or their salts in a total amount of 0.0025-0.25 grams as dibasic acids and / or polybasic acids, one or more aromatic alcohols in a total amount of 0.0015-0.050 grams, and one or more aromatic acids and / or their salts in a total amount of 0.0015-0.05 grams as aromatic acids; preferably, one or more fatty acids and / or their salts in a total amount of 0.00005-0.100 grams as fatty acids, one or more dibasic acids and / or their salts in a total amount of 0.005-0.175 grams as dibasic acids and / or polybasic acids, one or more aromatic alcohols in a total amount of 0.0015-0.035 grams, and one or more aromatic acids and / or their salts in a total amount of 0.0015-0.025 grams as aromatic acids per unit dosage form.

[0095] The various organic acids or their salts used in the preparation method of the present disclosure, such as fatty acids and / or their salts, or dibasic acids and / or their salts, or aromatic acids and / or their salts, and the like, are dissolved in water as un-ionized molecules and ionized ions, and the ratio of un-ionized molecules to ionized ions depends on the pH value of the solution and the ionization constant pKa value of the organic acid. It can be seen that after the organic acid and its salt are dissolved in water, they are both organic acid molecules or organic acid root ions, and from this perspective, there is no substantial difference between them. DETAILED DESCRIPTION

[0096] The following detailed description of various example embodiments of the application should not be considered to be limiting of the application, but rather a description of certain example aspects, features and embodiments of the application. It is understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the application. Additionally, for a numerical range recited in this disclosure, it is contemplated that each and every value and sub-range within the recited range is specifically included and explicitly made a part of this disclosure. The upper and lower limits of these smaller ranges can independently be included or excluded in the range.

[0097] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. Although preferred methods and materials are described, any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present application. All documents mentioned herein are incorporated by reference to disclose and describe in further detail the methods and / or materials associated with the documents. In the event of a conflict between the content of the specification and the documents incorporated herein by reference, the content of the specification controls. Unless otherwise indicated, "%" is a percentage by weight.

[0098] Antibacterial agents commonly used for skin and / or mucosa cleaning or bacteriostasis or disinfection, such as povidone iodine, chlorhexidine, etc., are mostly broad-spectrum antibacterial agents, which not only inhibit Escherichia coli, Staphylococcus aureus, fungi, etc., but also inhibit lactobacillus, etc. Lactic acid bacteria. The preservatives commonly used in skin care products, cosmetics, bath products, etc., and the preservatives commonly used in medical products, pharmaceuticals, such as chlorobutanol, benzalkonium chloride, etc., usually also have inhibitory effect on lactobacillus, etc. Lactic acid bacteria. There is still a lack of high selectivity antibacterial agents or antibacterial compositions that have strong inhibitory effect on harmful bacteria and weak inhibitory effect on lactobacillus, etc. Beneficial bacteria.

[0099] Prior art (e.g. PCT / CN2017 / 105296, ZL201080036139, US8765819) discloses some compositions by low concentration of antibacterial agents, such as low concentration of phenylethanol, propionic acid and / or its salt, and / or benzoic acid and / or its salt, etc. Combination, these compositions containing low concentration of antibacterial agents can inhibit Escherichia coli, Staphylococcus aureus, such as according to the test method and result judgment standard in the People's Republic of China national standard "Hygienic standard for disposable hygienic products" (GB15979-2002), the antibacterial rate of Escherichia coli and Staphylococcus aureus can reach more than 50%, and the antibacterial rate of Candida albicans is low, and the antibacterial rate is less than 50%.

[0100] Increasing the concentration of the bacteriostatic agent can enhance the bacteriostatic effect on Candida albicans. Studies have shown that appropriately increasing the concentration of each component in the bacteriostatic agent combination of "propionic acid and / or its salt + benzoic acid and / or its salt + phenethyl alcohol" can not only enhance the bacteriostatic effect of the bacteriostatic agent combination, but also more effectively inhibit Escherichia coli, Staphylococcus aureus, etc., and the inhibition rate on Candida albicans is also greater than 50%. However, the higher the concentration of the bacteriostatic agent, the stronger the inhibition effect on lactic acid bacteria such as lactobacillus. As shown in Example 1 disclosed in PCT / CN2017 / 105296, when the concentration of sodium propionate is 0.40% (w / v), 0.50% (w / v), the growth of lactobacillus is not significantly inhibited; when the concentration of sodium propionate is 0.70% (w / v), the growth of lactobacillus is inhibited. When the concentration of phenethyl alcohol is 0.40% (w / v), the growth of lactobacillus is not significantly inhibited; but when the concentration of phenethyl alcohol is 0.50% (w / v), the growth and acid production of lactobacillus are inhibited.

[0101] In order to further develop an effective bacteriostatic composition for inhibiting harmful microorganisms but not inhibiting lactobacillus and other beneficial bacteria, which can be used for skin and / or mucosa cleaning or bacteriostasis or disinfection, and can be used as a preservative for skin care products, cosmetics, bath products, etc., and as a preservative for medical products, pharmaceuticals, etc., the inventors have conducted in-depth research. It is found that appropriate fatty acids and / or their salts are selectively combined with dibasic acids, aromatic alcohols, aromatic acids, etc., not only have a synergistic bacteriostatic effect on Staphylococcus aureus and Escherichia coli, but also have a synergistic bacteriostatic effect on Candida albicans, etc., and the growth of Pseudomonas aeruginosa and Aspergillus niger is also significantly inhibited. The bacteriostatic composition prepared accordingly can significantly reduce the abnormal flora of the vagina and significantly increase lactobacillus when used in the vagina, and has the effect of regulating vaginal flora and vaginal acidity. Therefore, the bacteriostatic composition of the present disclosure can be used for skin and / or mucosa cleaning or bacteriostasis or disinfection; and for the preservation of bath products, skin care products, cosmetics, and for the preservation of medical products, pharmaceuticals, etc.

[0102] In order to facilitate the accurate meaning of the related terms or phrases or expressions or standards mentioned in this text, the meanings of the terms are defined as follows:

[0103] "Lactobacillus" refers to bacteria of the genus Lactobacillus, which is a gram-positive, rod-shaped, non-spore-forming bacterium that can ferment and metabolize sugars to produce a large amount of lactic acid. It contains hundreds of species and subspecies.

[0104] "Lactic acid bacteria" is a general term for bacteria that can metabolize fermentable carbohydrates to produce a large amount of lactic acid, and contains more than 200 species of bacteria in 18 genera. Among them, lactobacillus is also a kind of lactic acid bacteria.

[0105] "Normal vaginal flora" refers to the Nugent score of 1-3 for the vaginal flora. The bacteria in the vagina are mainly Lactobacillus, and the number of other types of bacteria is small. The "other types of bacteria" include Gram-positive cocci such as Staphylococcus, Streptococcus, etc., Gram-negative bacilli such as Gardnerella vaginalis, Escherichia coli, etc., Gram-negative cocci such as Veillonella, etc., obligate anaerobic Prevotella, Mobiluncus, etc.

[0106] "Abnormal vaginal flora" refers to the Nugent score of 5-10 for the vaginal flora. The number of Lactobacillus in the vagina is small, and the number of other types of bacteria is large. The "other types of bacteria" include Gram-positive cocci such as Staphylococcus, Streptococcus, etc., Gram-negative bacilli such as Gardnerella vaginalis, Escherichia coli, etc., Gram-negative cocci such as Veillonella, etc., obligate anaerobic Prevotella, Mobiluncus, etc.

[0107] "Harmful microorganisms" refer to various pathogenic microorganisms with strong pathogenicity, or various conditional pathogenic microorganisms that cause diseases when the immune system of the human body is weakened, or microorganisms that cause food, medicine, cosmetics, and sanitary products to spoil, including but not limited to the following microorganisms: Candida albicans, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Gardnerella vaginalis, Prevotella, Mobiluncus, Aspergillus niger, abnormal flora of skin and / or mucosa, and viruses HPV, HIV, etc.

[0108] "Components" refer to various ingredients in the composition, including bacteriostatic agents and other ingredients without bacteriostatic effect.

[0109] "Bacteriostatic agents" refer to various ingredients or combinations thereof with bacteriostatic effect, and are not limited to conventional bacteriostatic agents or combinations thereof recognized by those skilled in the art.

[0110] "Bacteriostatic rate" refers to the bacteriostatic rate of bacteriostatic agents on Escherichia coli, Staphylococcus aureus, Candida albicans, etc. according to the test method and judgment standard in Appendix C of GB 15979-2002 "Hygienic Standard for Disposable Sanitary Products".

[0111] "Bacteriostatic effect" refers to the inhibitory effect of bacteriostatic agents on bacteria, fungi, etc. In this document, the strength of the bacteriostatic effect is determined by the level of the bacteriostatic rate, as follows: > 50% for "bacteriostatic effect"; > 90% for "strong bacteriostatic effect".

[0112] "Low-concentration bacteriostatic agent" refers to a bacteriostatic agent with a bacteriostatic rate on Candida albicans < 50% and a relatively low concentration.

[0113] "High-concentration bacteriostatic agent" refers to a bacteriostatic agent with a bacteriostatic rate on Candida albicans > 50% and a relatively high concentration.

[0114] "no difference in bacteriostatic rate" or "no effect on bacteriostatic action" means a difference in bacteriostatic rates of < 15%.

[0115] "significant difference in bacteriostatic rate" or "significant effect on bacteriostatic action" means a difference in bacteriostatic rates of > 30%.

[0116] "significant difference in bacteriostatic rate" or "significant effect on bacteriostatic action" means a difference in bacteriostatic rates of > 30%.

[0117] "synergistic bacteriostatic action" means a combination of two or more bacteriostatic agents has a bacteriostatic rate on E. coli or S. aureus or C. albicans that is more than 15% higher than the sum of the bacteriostatic rates of each bacteriostatic agent acting alone.

[0118] Example 1

[0119] This example is a variety of exemplary compositions of bacteriostatic compositions. In the following, unless otherwise specifically stated, the exemplary components in the compositions refer to the following:

[0120] Propionic acid CAS: 79-09-4, Adipic acid CAS: 124-04-9, Phenyl ethanol (2-phenylethanol) CAS: 60-12-8, Butyric acid (n-butyric acid) CAS: 107-92-6, Caproic acid (n-caproic acid) CAS: 142-62-1, Pimelic acid CAS: 111-16-0, Malic acid (L-hydroxybutanedioic acid) CAS: 97-67-6, Cinnamic acid (trans-cinnamic acid) CAS: 140-10-3, Salicylic acid (2-hydroxybenzoic acid) CAS: 69-72-7, Lauric acid: n-dodecanoic acid CAS: 143-07-7, Valeric acid (n-valeric acid) CAS: 109-52-4, Heptanoic acid (n-heptanoic acid) CAS: 111-14-8, Octanoic acid (n-octanoic acid) CAS: 124-07-2, Nonanoic acid (n-nonanoic acid) CAS: 112-05-0, Decanoic acid (n-decanoic acid) CAS: 334-48-5, Undecanoic acid (undecylic acid) CAS: 112-37-8, Cinnamyl alcohol (3-phenyl-2-propen-l-ol) CAS: 104-54-1, Succinic acid (butanedioic acid) CAS: 110-15-6, Tartaric acid (L-tartaric acid) CAS: 87-69-4, Maleic acid (butenedioic acid) CAS: 110-16-7, Citric acid CAS: 77-92-9, Fumaric acid (butenedioic acid) CAS: 110-17-8, Undecylenic acid (10-undecenoic acid) CAS: 112-38-9, Glutaric acid CAS: 110-94-1.

[0121] Example 1:

[0122] Take adipic acid 1.50 grams, propionic acid 2.00 grams, phenethyl alcohol 0.25 grams, citric acid 1.00 grams, maltose 2.50 grams, add 80 grams of purified water, stir to dissolve adipic acid, propionic acid, phenethyl alcohol, citric acid, maltose, then add xanthan gum 2.15 grams, and make up with purified water to a total weight of 100 grams, stir to swell into a uniform sticky gel, adjust the pH to 3.1 with 1.0 mol / L sodium hydroxide solution, sterilize at 115.6°C for 15 minutes, and the water-soluble colloidal composition of the present disclosure is obtained.

[0123] Example 2:

[0124] The raw materials were weighed according to the following proportions, and 100 grams of composition was prepared according to the method of Example 1:

[0125]

[0126] Example 3:

[0127] The raw materials were weighed according to the following proportions, and 100 grams of composition was prepared according to the method of Example 1:

[0128]

[0129] Example 4:

[0130] The raw materials were weighed according to the following proportions, and 100 grams of composition was prepared according to the method of Example 1:

[0131]

[0132] Example 5:

[0133] The raw materials were weighed according to the following proportions, and 100 grams of composition was prepared according to the method of Example 1:

[0134]

[0135] Example 6:

[0136] The raw materials were weighed according to the following proportions, and 100 grams of composition was prepared according to the method of Example 1:

[0137]

[0138]

[0139] Example 7:

[0140] The raw materials were weighed according to the following proportions, and 100 grams of composition was prepared according to the method of Example 1:

[0141]

[0142] Example 8:

[0143] The ingredients were weighed out in the proportions given below and 100 g of composition was prepared essentially as in Example 1.

[0144]

[0145] Example 9:

[0146] The ingredients were weighed out in the proportions given below and 100 g of composition was prepared essentially as in Example 1.

[0147] Benzoic acid 1.00 g

[0148] Phenyl ethyl alcohol 0.50 g

[0149] Add purified water to 100 g

[0150] Adjust pH to 4.8

[0151] Example 10:

[0152] The ingredients were weighed out in the proportions given below and 100 g of composition was prepared essentially as in Example 1.

[0153]

[0154] Example 11:

[0155] The ingredients were weighed out in the proportions given below and 100 g of composition was prepared essentially as in Example 1.

[0156]

[0157] Example 12:

[0158] The ingredients were weighed out in the proportions given below and 100 g of composition was prepared essentially as in Example 1.

[0159]

[0160]

[0161] Example 13:

[0162] The ingredients were weighed out in the proportions given below and 100 g of composition was prepared essentially as in Example 1.

[0163]

[0164] Example 14:

[0165] The ingredients were weighed out in the proportions given below and 100 g of composition was prepared essentially as in Example 1.

[0166] Adipic acid 1.50 g, benzoic acid 0.20 g, propionic acid 1.25 g;

[0167] Glutamic acid 0.76 g, glutamine 0.34 g, aspartic acid 0.60 g, asparagine 0.98 g, isoleucine 0.31 g, methionine 0.35 g, phenylalanine 0.20 g, valine 0.46 g, leucine 0.78 g, proline 0.89 g;

[0168] Xanthan gum 2.50 g, add purified water to a total weight of 100 g, pH adjusted to 4.0

[0169] Example 15

[0170] The raw materials were weighed according to the following proportions, and a 100 g composition was prepared according to the method of Example 1.

[0171]

[0172]

[0173] Example 16

[0174] According to the method of Reference 1, tablets were prepared, each containing 60 mg of adipic acid, 5 mg of sodium benzoate, 30 mg of propionic acid, and 60 mg of sucrose.

[0175] Example 17

[0176] According to the method of Reference 3, vaginal suppositories were prepared, each containing 60 mg of adipic acid, 5 mg of sodium benzoate, 30 mg of propionic acid, and 60 mg of maltose.

[0177] Example 2

[0178] This example is used to verify the effect of the composition.

[0179] In vitro experiment one

[0180] According to the method of Appendix C of GB 15979-2002 "Hygienic Standard for Disposable Hygienic Products", the bacteriostatic rate of different component combinations on Candida albicans ATCC 10231 was studied after 20 minutes of action, wherein the percentage concentration of each component was weight percentage concentration % (w / w), and the pH value was 3.8. The experimental results are shown in Table 1:

[0181] Table 1 Bacteriostatic effect of different solution combinations on Candida albicans ATCC 10231

[0182] No. Propionic acid (%) Adipic acid (%) Benzyl alcohol (%) Sodium benzoate (%) Bacteriostatic rate (%) 1 0.50 1.50 -- 0.20 61.29 2 0.50 1.50 0.50 0.20 81.52 3 0.50 1.50 0.70 0.20 99.27

[0183] The results show that:

[0184] 1. As shown in Table 1, the solution of the combination of 0.50% propionic acid, 1.50% adipic acid and 0.20% sodium benzoate has inhibitory effect on Candida albicans at pH 3.8, and the inhibitory rate is 61.29%.

[0185] 2. As shown in Table 1, the solution of the combination of 0.50% propionic acid, 1.50% adipic acid and 0.20% sodium benzoate has inhibitory effect on Candida albicans at pH 3.8, and the inhibitory rate is 61.29%.

[0186] As shown in Table 1, the solution of the combination of 0.50% propionic acid, 1.50% adipic acid and 0.20% sodium benzoate has inhibitory effect on Candida albicans at pH 3.8, and the inhibitory rate is 61.29%.

[0187] In vitro experiment two

[0188] According to the method of Appendix C of GB 15979-2002 "Hygienic Standard for Disposable Hygienic Products", the inhibitory rate of Candida albicans ATCC 10231 treated with different component combinations for 20 minutes was studied, wherein the percentage concentration of each component was weight percentage concentration (w / w), and the pH value was 4.0. The experimental results are shown in Table 2.

[0189] Table 2 Inhibitory effect of different solution combinations on Candida albicans ATCC 10231

[0190] No. Propionic acid (%) Adipic acid (%) Phenyl ethanol (%) Benzoic acid (%) Bacteriostatic rate (%) 1 1.50 -- 0.35 0.20 15.91 2 1.50 -- 0.35 0.25 46.09 3 1.50 1.50 0.35 0.20 67.39 4 1.50 1.50 0.35 0.25 92.17

[0191] The results show that:

[0192] 1. As shown in Table 2, the solution of the combination of 1.50% propionic acid, 0.35% phenethyl alcohol and 0.20% benzoic acid has inhibitory effect on Candida albicans at pH 4.0, and the inhibitory rate is 15.91%.

[0193] 2. As shown in Table 2, the solution of the combination of 1.50% propionic acid, 0.35% phenethyl alcohol and 0.25% benzoic acid has inhibitory effect on Candida albicans at pH 4.0, and the inhibitory rate is 46.09%.

[0194] 3. As shown in Table 2, the solution of the combination of 1.50% propionic acid, 1.50% adipic acid, 0.35% phenethyl alcohol and 0.20% benzoic acid has inhibitory effect on Candida albicans at pH 4.0, and the inhibitory rate is 67.39%.

[0195] 4. From the results of the 4th group in Table 2, it can be seen that the solution of 1.50% propionic acid, 1.50% adipic acid, 0.35% phenethyl alcohol and 0.25% benzoic acid has strong inhibitory effect on Candida albicans at pH 4.0, and the inhibitory rate is 92.17%.

[0196] In summary:

[0197] 1. From the results of the 1st group and the 2nd group, and the 3rd group and the 4th group, it can be seen that the increase of the concentration of benzoic acid from 0.20% to 0.25% has influence or significant influence on the inhibitory effect of the solution containing "1.50% propionic acid, 0.35% phenethyl alcohol" and the solution containing "1.50% propionic acid, 1.50% adipic acid, 0.35% phenethyl alcohol" on Candida albicans at pH 4.0, and the inhibitory effect is enhanced.

[0198] 2. From the results of the 1st group and the 3rd group, and the 2nd group and the 4th group, it can be seen that 1.50% adipic acid has significant influence on the inhibitory effect of the solution of "1.50% propionic acid, 0.35% phenethyl alcohol, 0.20% benzoic acid" and "1.50% propionic acid, 0.35% phenethyl alcohol, 0.25% benzoic acid" on Candida albicans at pH 4.0, and the inhibitory effect is enhanced.

[0199] In vitro experiment three

[0200] According to the method of Appendix C of GB 15979-2002 "Hygienic Standard for Disposable Hygienic Products", the inhibitory rate of Candida albicans ATCC 10231 was studied after being treated with different component combinations for 20 minutes, wherein the percentage concentration of each component was weight percentage concentration % (w / w), and the pH value was 3.8. The experimental results are shown in Table 3:

[0201] Table 3 Inhibitory effect of different solution combinations on Candida albicans ATCC 10231

[0202] No. Propionic acid (%) Adipic acid (%) Benzyl alcohol (%) Sodium benzoate (%) Bacteriostatic rate (%) 1 -- 1.35 0.25 0.20 45.12 2 0.50 1.35 0.25 0.20 61.60 3 1.25 1.35 0.25 0.20 89.72 4 1.50 1.35 0.25 0.20 94.42 5 3.00 1.35 0.25 0.20 100.00

[0203] The results show that:

[0204] 1. From the results of the 1st group in Table 3, it can be seen that the solution of 1.35% adipic acid, 0.25% benzyl alcohol and 0.20% sodium benzoate has an inhibitory rate of 45.12% on Candida albicans at pH 3.8.

[0205] 2. From the results of the experiments of groups 2-5 in Table 3, it can be seen that the solutions of 4 different concentrations of propionic acid (0.50%, 1.25%, 1.50%, 3.00%) combined with "1.35% adipic acid, 0.25% benzyl alcohol, 0.20% sodium benzoate" respectively have inhibitory effect or strong inhibitory effect on Candida albicans at pH 3.8, and the inhibitory rates are 61.60%, 89.72%, 94.42%, and 100.00% respectively.

[0206] In summary, comparing groups 2-5 and group 1, the effect of propionic acid on the inhibition of Candida albicans in the solution containing "1.35% adipic acid, 0.25% benzyl alcohol, 0.20% sodium benzoate" has an influence or a significant influence at pH 3.8, the inhibitory effect is enhanced, and the higher the concentration of propionic acid, the stronger the inhibitory effect on Candida albicans.

[0207] In vitro experiment four

[0208] According to the method of Appendix C of GB 15979-2002 "Hygienic Standard for Disposable Hygienic Products", the inhibitory rates of Candida albicans ATCC 10231 treated with different component combinations for 20 minutes were studied, wherein the percentage concentrations of each component were weight percentage concentrations (w / w), and the pH values were all 4.3. The experimental results are shown in Table 4:

[0209] Table 4 Inhibitory effect of different solution combinations on Candida albicans ATCC 10231

[0210] No. Propionic acid (%) Adipic acid (%) Phenyl ethanol (%) Benzoic acid (%) Bacteriostatic rate (%) 1 0.54 1.50 0.30 -- 26.05 2 0.54 1.50 0.30 0.50 64.80 3 0.54 1.50 0.30 1.00 100.00

[0211] The results show that:

[0212] 1. From the results of the experiments of group 1 in Table 4, it can be seen that the solution of 0.54% propionic acid, 1.50% adipic acid, and 0.30% phenethyl alcohol has an inhibitory rate of 26.05% on Candida albicans at pH 4.3.

[0213] 2. From the results of the experiments of groups 2 and 3 in Table 4, it can be seen that the solutions of "0.54% propionic acid, 1.50% adipic acid, 0.30% phenethyl alcohol" combined with 0.50% and 1.00% benzoic acid respectively have inhibitory effect or strong inhibitory effect on Candida albicans at pH 4.3, and the inhibitory rates are 64.80% and 100.00% respectively.

[0214] In summary, the effect of 0.50% and 1.00% benzoic acid on the inhibition of Candida albicans in the solution containing "0.54% propionic acid, 1.50% adipic acid, 0.30% phenethyl alcohol" has a significant influence at pH 4.3, the inhibitory effect is enhanced, and the higher the concentration of benzoic acid, the stronger the inhibitory effect on Candida albicans.

[0215] In vitro experiment five

[0216] The bacteriostatic rate of different solution combinations on Candida albicans ATCC 10231 was studied according to the method of Appendix C of GB 15979-2002 "Hygienic standard for single-use hygienic products", and the solutions were allowed to act on Candida albicans ATCC 10231 for 20 minutes, wherein the percentage concentration of each component was weight percentage concentration % (w / w), and the pH value was 4.6. The experimental results are shown in Table 5:

[0217] Table 5 Bacteriostatic effect of different solution combinations on Candida albicans ATCC 10231

[0218] No. Propionic acid (%) Adipic acid (%) Phenyl ethanol (%) Sodium benzoate (%) Bacteriostatic rate (%) 1 -- 1.50 0.30 1.18 84.12 2 2.00 1.50 0.30 1.18 100.00

[0219] The results show that:

[0220] 1. As can be seen from the experimental results of Table 5, at pH 4.6, the solution of 1.50% adipic acid, 0.30% phenylethanol, and 1.18% sodium benzoate has bacteriostatic effect on Candida albicans, and the bacteriostatic rate is 84.12%;

[0221] 2. As can be seen from the experimental results of Table 5, at pH 4.6, the solution of 2.00% propionic acid, 1.50% adipic acid, 0.30% phenylethanol, and 1.18% sodium benzoate has strong bacteriostatic effect on Candida albicans, and the bacteriostatic rate is 100.00%.

[0222] In summary, comparing the experimental results of the first group and the second group, it can be seen that at pH 4.6, 2.00% propionic acid has an effect on the solution containing "1.50% adipic acid, 0.30% phenylethanol, and 1.18% sodium benzoate" to inhibit Candida albicans, and the bacteriostatic effect is enhanced.

[0223] In vitro experiment six

[0224] The bacteriostatic rate of different solution combinations on Candida albicans ATCC 10231 was studied according to the method of Appendix C of GB 15979-2002 "Hygienic standard for single-use hygienic products", and the solutions were allowed to act on Candida albicans ATCC 10231 for 20 minutes, wherein the percentage concentration of each component was weight percentage concentration % (w / w), and the pH value was 4.6. The experimental results are shown in Table 5:

[0225] Table 6 Bacteriostatic effect of different solutions on Candida albicans ATCC 10231

[0226]

[0227]

[0228] The results show that:

[0229] 1. As can be seen from the experimental results of groups 1-2 in Table 6, at pH 3.8, the solutions of "0.20% sodium benzoate and 0.40% phenylethanol" combined with two different concentrations of fatty acids (0.88% butyric acid and 0.12% hexanoic acid) have an inhibitory effect on Candida albicans, with inhibition rates of 71.52% and 70.65%, respectively.

[0230] 2. As can be seen from the experimental results of groups 3-4 in Table 6: at pH 3.8, the combined solution of "0.20% sodium benzoate, 0.40% phenoxyethanol, and 0.88% butyric acid" has an inhibitory effect on Candida albicans, with an inhibition rate of 56.75%; the combined solution of "0.20% sodium benzoate, 0.40% phenoxyethanol, and 0.12% hexanoic acid" has an inhibition rate of 35.88% on Candida albicans.

[0231] 3. As can be seen from the experimental results of groups 5-6 in Table 6, at pH 3.8, the solutions of "1.46% adipic acid, 0.20% sodium benzoate, and 0.40% phenylethanol" combined with two different concentrations of fatty acids (0.88% butyric acid and 0.12% hexanoic acid) have a strong inhibitory effect on Candida albicans, with an inhibition rate of 100% in each case.

[0232] 4. As can be seen from the experimental results of groups 7-8 in Table 6, at pH 3.8, the solutions of "1.46% adipic acid, 0.20% sodium benzoate, and 0.40% phenoxyethanol" combined with two different concentrations of fatty acids (0.88% butyric acid and 0.12% hexanoic acid) have a strong inhibitory effect on Candida albicans, with an inhibition rate of 100% in each case.

[0233] In summary,

[0234] 1. Comparing the experimental results of groups 5-6 and 1-2 in Table 6, it can be seen that at pH 3.8, 1.46% adipic acid has a significant effect on the inhibition of Candida albicans by the solutions of "0.20% sodium benzoate, 0.40% phenylethanol, 0.88% butyric acid" and "0.20% sodium benzoate, 0.40% phenylethanol, 0.12% hexanoic acid", respectively, and the antibacterial effect is enhanced.

[0235] 2. As can be seen from the experimental results of groups 7-8 and 3-4 in Table 6, at pH 3.8, 1.46% adipic acid has a significant effect on the inhibition of Candida albicans by the solutions of the combinations of "0.20% sodium benzoate, 0.40% phenoxyethanol, 0.88% butyric acid" and "0.20% sodium benzoate, 0.40% phenoxyethanol, 0.12% hexanoic acid", respectively, and the antibacterial effect is enhanced.

[0236] In vitro experiment seven

[0237] Following the methods outlined in Appendix C of GB15979-2002 "Hygienic Standard for Disposable Sanitary Products," the inhibition rates of different component combinations against *Candida albicans* ATCC 10231 were studied after 20 minutes of contact with the solution. All component concentrations were expressed as weight percentages (w / w), and the pH value was 3.8. The experimental results are shown in Table 7.

[0238] Table 7. Antibacterial effects of different solutions on Candida albicans ATCC 10231

[0239] No. Propionic acid (%) Pimelic acid (%) Malic acid (%) Phenyl ethanol (%) p-Hydroxy benzoic acid (%) Bacteriostatic rate (%) 1 2.50 -- -- 0.06 0.21 62.76 2 2.50 1.60 -- 0.06 0.21 94.84 3 2.50 -- 1.34 0.06 0.21 65.68

[0240] The results show:

[0241] 1. As can be seen from the experimental results of Group 1 in Table 7, at pH 3.8, the solution of the three components "0.21% p-hydroxybenzoic acid, 0.06% phenylethanol, and 2.50% propionic acid" has an inhibitory effect on Candida albicans, with an inhibition rate of 62.76%.

[0242] 2. As can be seen from the experimental results in Group 2 of Table 7, at pH 3.8, the solution of 1.60% pimelic acid combined with "0.21% p-hydroxybenzoic acid, 0.06% phenylethanol, and 2.50% propionic acid" has a strong inhibitory effect on Candida albicans, with an inhibition rate of 94.84%.

[0243] 3. As can be seen from the experimental results of Group 3 in Table 7, at pH 3.8, the solution of 1.34% malic acid combined with "0.21% p-hydroxybenzoic acid, 0.06% phenylethanol and 2.50% propionic acid" has an inhibitory effect on Candida albicans, with an inhibition rate of 65.68%.

[0244] In summary, comparing the experimental results of groups 2 and 3 with those of group 1, it can be seen that at pH 3.8, 1.60% pimelic acid significantly affects the inhibitory effect of the solution containing the combination of "0.21% p-hydroxybenzoic acid, 0.06% phenylethanol, and 2.50% propionic acid" on Candida albicans, enhancing its antibacterial effect; while 1.34% malic acid has no effect on the inhibitory effect of the solution containing the combination of "0.21% p-hydroxybenzoic acid, 0.06% phenylethanol, and 2.50% propionic acid" on Candida albicans.

[0245] In vitro experiment eight

[0246] Following the methods outlined in Appendix C of GB 15979-2002 "Hygienic Standard for Disposable Sanitary Products," the inhibitory effects of aqueous solutions containing different components on *Candida albicans* ATCC10231 were studied after 20 minutes of treatment. All component concentrations were expressed as weight percentages (w / w), and the pH value was 3.9. The experimental results are shown in Table 8.

[0247] Table 8. Antibacterial effects of different solutions on Candida albicans ATCC10231

[0248] No. Adipic acid (%) Butyric acid (%) Sodium benzoate (%) Phenyl ethanol (%) Bacteriostatic rate (%) 1 1.46 -- -- -- 11.52 2 -- 0.60 -- -- 1.57 3 -- -- 0.14 -- 19.90 4 -- -- -- 0.40 -1.05 5 1.46 0.60 -- -- 13.61 6 -- 0.60 0.14 -- 17.80 7 -- 0.60 -- 0.40 8.90 8 1.46 0.60 0.14 -- 27.23 9 1.46 0.60 -- 0.40 25.65 10 -- 0.60 0.14 0.40 2.62 11 1.46 -- 0.14 0.40 42.41 12 1.46 0.60 0.14 0.40 89.53

[0249] The results show:

[0250] 1. As can be seen from the experimental results of groups 1-4 in Table 8: at pH 3.9, the inhibition rates of 1.46% adipic acid, 0.60% butyric acid, 0.14% sodium benzoate, and 0.40% phenylethanol against Candida albicans were 11.52%, 1.57%, 19.90%, and -1.05%, respectively, when used individually.

[0251] 2. As can be seen from the experimental results of Group 5 in Table 8, at pH 3.9, the solution of "1.46% adipic acid and 0.60% butyric acid" had an inhibition rate of 13.61% against Candida albicans.

[0252] 3. As can be seen from the experimental results of Group 6 in Table 8, at pH 3.9, the solution of "0.60% butyric acid and 0.14% sodium benzoate" had an inhibition rate of 17.80% against Candida albicans.

[0253] 4. As can be seen from the experimental results of Group 7 in Table 8, at pH 3.9, the solution of "0.60% butyric acid and 0.40% phenylethanol" had an inhibition rate of 8.90% against Candida albicans.

[0254] 5. As can be seen from the experimental results of Group 8 in Table 8, at pH 3.9, the solution of the combination of "1.46% adipic acid, 0.60% butyric acid, and 0.14% sodium benzoate" had an inhibition rate of 27.23% against Candida albicans.

[0255] 6. As can be seen from the experimental results in Group 9 of Table 8, at pH 3.9, the solution of "1.46% adipic acid, 0.60% butyric acid, and 0.40% phenylethanol" had an inhibition rate of 25.65% against Candida albicans.

[0256] 7. As can be seen from the experimental results of Group 10 in Table 8, at pH 3.9, the solution of the combination of "0.60% butyric acid, 0.40% phenylethanol, and 0.14% sodium benzoate" had an inhibition rate of 2.62% against Candida albicans.

[0257] 8. As can be seen from the experimental results of Group 11 in Table 8, at pH 3.9, the solution of "1.46% adipic acid, 0.14% sodium benzoate, and 0.40% phenylethanol" has an inhibition rate of 42.41% against Candida albicans.

[0258] 9. As can be seen from the experimental results of Group 12 in Table 8, at pH 3.9, the solution of "1.46% adipic acid, 0.60% butyric acid, 0.14% sodium benzoate and 0.40% phenylethanol" has an inhibitory effect on Candida albicans, with an inhibition rate of 89.53%.

[0259] In summary, it is evident that at pH 3.9, the combination of four components—1.46% adipic acid, 0.60% butyric acid, 0.14% sodium benzoate, and 0.40% phenylethanol—exhibited a significantly higher inhibition rate against Candida albicans than the individual, paired, or combined effects of the aforementioned components. This suggests that the combination of these four components exhibits a synergistic antibacterial effect against Candida albicans.

[0260] In vitro experiment nine

[0261] Following the methods outlined in Appendix C of GB 15979-2002 "Hygienic Standard for Disposable Sanitary Products," the inhibitory effects of aqueous solutions containing different component combinations on *Candida albicans* ATCC10231 were studied after 20 minutes of treatment. All component concentrations were expressed as weight percentages (w / w), and the solution pH was 4.3. The experimental results are shown in Table 9.

[0262] Table 9. Antibacterial effects of different solutions on Candida albicans ATCC10231

[0263] No. Caproic acid (%) Adipic acid (%) Sodium benzoate (%) Phenyl ethanol (%) Bacteriostatic rate (%) 1 0.18 -- -- -- 2.82 2 -- 1.35 -- -- 5.81 3 -- -- 0.20 -- 6.95 4 -- -- -- 0.30 0.59 5 0.18 1.35 0.20 0.30 58.86 6 0.18 1.35 0.20 -- 25.17 7 0.18 1.35 -- 0.30 9.33 8 -- 1.35 0.20 0.30 15.37 9 0.18 -- 0.20 0.30 28.78

[0264] The results show:

[0265] 1. As can be seen from the experimental results of groups 1-4 in Table 9, at pH 4.3, the inhibition rate of the four components 1.35% adipic acid, 0.20% sodium benzoate, 0.18% hexanoic acid and 0.30% phenylethanol against Candida albicans was <10% when used alone.

[0266] 2. As can be seen from the experimental results of Group 5 in Table 9, at pH 4.3, the solution of the four components "1.35% adipic acid, 0.20% sodium benzoate, 0.18% hexanoic acid, and 0.30% phenylethanol" has an inhibitory effect on Candida albicans, with an inhibition rate of 58.86%.

[0267] 3. As can be seen from the experimental results of groups 6-9 in Table 9, at pH 4.3, the inhibition rate of Candida albicans in any combination of the four components (1.35% adipic acid, 0.20% sodium benzoate, 0.18% hexanoic acid, and 0.30% phenylethanol) is less than 50%.

[0268] In summary, it is evident that the solution containing the four components—1.35% adipic acid, 0.20% sodium benzoate, 0.18% hexanoic acid, and 0.30% phenylethanol—exhibited a significantly higher inhibition rate against Candida albicans than any combination of any three components, and was also significantly higher than the sum of the inhibition rates of the four components acting individually. This suggests that these four components have a synergistic antibacterial effect against Candida albicans.

[0269] In vitro experiments 10

[0270] Following the methods outlined in Appendix C of GB 15979-2002 "Hygienic Standard for Disposable Sanitary Products," the inhibitory effects of aqueous solutions containing different component combinations on *Candida albicans* ATCC10231 were studied after 20 minutes of treatment. All component concentrations were expressed as weight percentages (w / w), and the solution pH was 3.8. The experimental results are shown in Table 10.

[0271] Table 10. Antibacterial effects of Candida albicans ATCC10231 in different solutions.

[0272]

[0273]

[0274] The results show:

[0275] 1. As can be seen from the experimental results in Group 1 of Table 10, at pH 3.8, the solution of the combination of 1.50% adipic acid, 0.45% phenylethanol and 1.50% propionic acid had an inhibition rate of 30.96% against Candida albicans.

[0276] 2. As can be seen from the experimental results of groups 2-5 in Table 10, at pH 3.8, solutions of four different concentrations of cinnamic acid (0.03%, 0.05%, 0.08%, and 0.10%) combined with "1.50% adipic acid, 0.45% phenylethanol, and 1.50% propionic acid" showed inhibitory or strong inhibitory effects on Candida albicans, with inhibition rates of 59.04%, 71.19%, 96.38%, and 100.00%, respectively.

[0277] 3. As shown in the experimental results of groups 6-9 in Table 10, at pH 3.8, the solution of 0.03% salicylic acid combined with "1.50% adipic acid, 0.45% phenylethanol, and 1.50% propionic acid" had an inhibition rate of 37.40% against Candida albicans. The solutions of three higher concentrations of salicylic acid (0.05%, 0.08%, and 0.10%) combined with "1.50% adipic acid, 0.45% phenylethanol, and 1.50% propionic acid" respectively had an inhibitory effect or a strong inhibitory effect on Candida albicans, with inhibition rates of 55.58%, 86.96%, and 94.81%, respectively.

[0278] In summary, it can be seen that 0.03-0.10% cinnamic acid and 0.05-0.10% salicylic acid have an effect or a significant effect on the inhibitory effect of the solution containing the combination of "1.50% adipic acid, 0.45% phenylethanol, and 1.50% propionic acid" on Candida albicans, and the antibacterial effect increases with the increase of the concentration of cinnamic acid or salicylic acid.

[0279] In vitro experiment eleven

[0280] Following the methods outlined in Appendix C of GB 15979-2002 "Hygienic Standard for Disposable Sanitary Products," the inhibitory effects of aqueous solutions containing different component combinations on *Candida albicans* ATCC10231 were studied after 20 minutes of treatment. All component concentrations were expressed as weight percentages (w / w), and the solution pH was 3.8. The experimental results are shown in Table 11.

[0281] Table 11. Antibacterial effects of different solutions on Candida albicans ATCC10231

[0282]

[0283]

[0284] The results show:

[0285] 1. As can be seen from the experimental results of groups 1-6 in Table 11, at pH 3.8, the inhibition rate of 0.001-0.002% undecanoic acid, 0.001-0.002% undecenoic acid, and 0.001-0.002% lauric acid alone against Candida albicans was less than 15%.

[0286] 2. As can be seen from the experimental results of Group 7 in Table 11, at pH 3.8, the solution of the three components "0.20% sodium benzoate, 0.25% phenylethanol, and 1.50% adipic acid" has an inhibitory effect on Candida albicans, with an inhibition rate of 50.02%.

[0287] 3. As can be seen from the experimental results of groups 8-9 in Table 11, at pH 3.8, the solutions of the three components "0.20% sodium benzoate, 0.25% phenylethanol, and 1.50% adipic acid" combined with two different concentrations of undecanoic acid (0.001% and 0.002%) showed strong antibacterial effects against Candida albicans, with inhibition rates all exceeding 90%.

[0288] 4. As can be seen from the experimental results of groups 10-11 in Table 11, at pH 3.8, the solutions of the three components "0.20% sodium benzoate, 0.25% phenylethanol, and 1.50% adipic acid" combined with two different concentrations of undecenoic acid (0.001% and 0.002%) have an inhibitory effect on Candida albicans, with an inhibition rate of more than 50%.

[0289] 5. As can be seen from the experimental results of groups 12-13 in Table 11, at pH 3.8, the solutions of the three components "0.20% sodium benzoate, 0.25% phenylethanol, and 1.50% adipic acid" combined with two different concentrations of lauric acid (0.001% and 0.002%) showed strong antibacterial effects against Candida albicans, with an inhibition rate of 100% in both cases.

[0290] In summary, it can be seen that 0.001-0.002% undecanoic acid, 0.002% undecenoic acid, and 0.001-0.002% lauric acid have significant effects on the inhibitory effect of solutions containing the combination of "0.20% sodium benzoate, 0.25% phenylethanol, and 1.50% adipic acid" on Candida albicans, and the antibacterial effect is enhanced.

[0291] In vitro experiment twelve

[0292] Following the methods outlined in Appendix C of GB 15979-2002 "Hygienic Standard for Disposable Sanitary Products," the inhibitory effects of aqueous solutions containing different component combinations on *Candida albicans* ATCC10231 were studied after 20 minutes of treatment. All component concentrations are expressed as weight percentages (w / w). The experimental results are shown in Table 12-14.

[0293] Table 12. Antibacterial effects of different solutions alone on Candida albicans ATCC 10231

[0294]

[0295] Table 13. Antibacterial effects of solutions containing different combinations of components on Candida albicans ATCC 10231

[0296]

[0297] Table 14. Antibacterial effects of three different component combinations on Candida albicans ATCC 10231

[0298]

[0299]

[0300] The results show:

[0301] 1. As can be seen from the experimental results in Table 12, at pH values ​​of 3.6-3.8, the inhibition rates of 10 different concentrations of fatty acids (2.00% propionic acid, 2.20% butyric acid, 0.60% valeric acid, 0.20% hexanoic acid, 0.07% heptanoic acid, 0.02% octanoic acid, 0.009% nonanoic acid, 0.002% decanoic acid, 0.001% undecanoic acid, 0.001% lauric acid) and 0.25% sodium benzoate, when used alone, were all <20% against Candida albicans.

[0302] 2. As shown in Table 13, at pH values ​​of 3.6-3.8, solutions of 0.20-0.25% sodium benzoate combined with 10 different concentrations of fatty acids (2.00% propionic acid, 2.20% butyric acid, 0.60% valeric acid, 0.20% hexanoic acid, 0.07% heptanoic acid, 0.02% octanoic acid, 0.009% nonanoic acid, 0.002% decanoic acid, 0.001% undecanoic acid, and 0.001% lauric acid) exhibit antibacterial activity against Candida albicans, with inhibition rates all >50%. This suggests that the combination of these two components has a synergistic antibacterial effect against Candida albicans, enhancing the antibacterial activity.

[0303] 3. As shown in Table 14, at pH values ​​of 3.6-3.8, solutions of "0.20% sodium benzoate, 0.40% phenylethanol" combined with 10 different concentrations of fatty acids (2.00% propionic acid, 2.20% butyric acid, 0.60% valeric acid, 0.20% hexanoic acid, 0.07% heptanoic acid, 0.02% octanoic acid, 0.009% nonanoic acid, 0.002% decanoic acid, 0.001% undecanoic acid, and 0.001% lauric acid) exhibit antibacterial activity or strong antibacterial activity against Candida albicans, with inhibition rates between 50% and 90% or >90%. This suggests that the combination of these three components has a synergistic antibacterial effect against Candida albicans, with enhanced antibacterial activity.

[0304] In vitro experiment thirteen

[0305] Following the methods outlined in Appendix C of GB 15979-2002 "Hygienic Standard for Disposable Sanitary Products," the inhibitory effects of aqueous solutions containing different component combinations on *Candida albicans* ATCC10231 were studied after 20 minutes of treatment. All component concentrations were expressed as weight percentages (w / w), and the pH value was 3.8. The experimental results are shown in Table 15.

[0306] Table 15. Antibacterial effects of different solutions on Candida albicans ATCC 10231

[0307]

[0308]

[0309] The results show:

[0310] 1. As can be seen from the experimental results of groups 1-10 in Table 15, at pH 3.8, the inhibition rates of nine different concentrations of fatty acids (2.00% propionic acid, 2.20% butyric acid, 0.60% valeric acid, 0.20% hexanoic acid, 0.07% heptanoic acid, 0.02% octanoic acid, 0.005% decanoic acid, 0.003% lauric acid, and 0.003% undecanoic acid) and 0.30% cinnamyl alcohol on Candida albicans were all less than 25% when used alone.

[0311] 2. As can be seen from the experimental results of groups 11-19 in Table 15, at pH 3.8, solutions of nine different concentrations of fatty acids (2.00% propionic acid, 2.2% butyric acid, 0.60% valeric acid, 0.20% hexanoic acid, 0.07% heptanoic acid, 0.02% octanoic acid, 0.005% decanoic acid, 0.003% lauric acid, and 0.003% undecanoic acid) combined with 0.30% cinnamyl alcohol have antibacterial effects or strong antibacterial effects against Candida albicans, with inhibition rates between 50-90% or >90%. This suggests that the combination of these two components has a synergistic antibacterial effect against Candida albicans, and the antibacterial effect is enhanced.

[0312] In vitro experiment fourteen

[0313] Following the methods outlined in Appendix C of GB15979-2002 "Hygienic Standard for Disposable Sanitary Products", the inhibition rates of different component combinations against Candida albicans ATCC 10231 were studied after 20 minutes of contact with the solution. All component concentrations are expressed as weight percentages (w / w), and the pH value was 3.8. The experimental results are shown in Table 16.

[0314] Table 16. Antibacterial effects of different solution combinations on Candida albicans ATCC 10231

[0315] No. Butyric acid (%) Pimelic acid (%) Phenyl ethanol (%) Bacteriostatic rate (%) 1 1.00 -- -- 1.22 2 -- 1.00 -- 2.09 3 -- -- 0.60 4.98 4 1.00 -- 0.60 11.09 5 1.00 1.00 0.60 65.22

[0316] The results show:

[0317] 1. As can be seen from the experimental results of groups 1-3 in Table 16, at pH 3.8, the inhibition rate of 1.00% butyric acid, 1.00% pimelic acid and 0.60% phenylethanol against Candida albicans was <10% when used alone.

[0318] 2. As can be seen from the experimental results of Group 4 in Table 16: at pH 3.8, the solution of 1.00% butyric acid and 0.60% phenylethanol had an inhibition rate of 11.09% against Candida albicans.

[0319] 3. As can be seen from the experimental results of Group 5 in Table 16, at pH 3.8, the solution of 1.00% butyric acid, 1.00% pimelic acid and 0.60% phenylethanol has an inhibitory effect on Candida albicans, with an inhibition rate of 65.22%.

[0320] In summary, it can be seen that the solution of 1.00% pimelic acid, 1.00% butyric acid, and 0.60% phenylethanol has a synergistic antibacterial effect on Candida albicans, and the antibacterial effect is enhanced.

[0321] Experimental Example 15

[0322] Following the methods outlined in Appendix C of GB 15979-2002 "Hygienic Standard for Disposable Sanitary Products," the inhibitory effect of sodium propionate combined with a dicarboxylic acid / tricarboxylic acid solution on *Candida albicans* ATCC10231 was experimentally investigated after 20 minutes of contact. All components were expressed as weight percentages (w / w), and the solution pH was 3.6. The experimental results are shown in Table 17.

[0323] Table 17. Antibacterial effects of solutions with different component combinations on Candida albicans ATCC10231

[0324]

[0325]

[0326] The results show:

[0327] 1. As can be seen from the experimental results of groups 1-8 in Table 17, at pH 3.6, the inhibition rate of 2.88% sodium propionate and 7 different concentrations of dicarboxylic acid or polycarboxylic acid (4.38% adipic acid, 3.54% succinic acid, 4.02% malic acid, 4.50% tartaric acid, 3.50% maleic acid, 5.76% citric acid, and 3.50% fumaric acid) against Candida albicans was <25% when used alone.

[0328] 2. As can be seen from the experimental results of Group 9 in Table 17, at pH 3.6, the solution of 1.25% sodium propionate and 4.38% adipic acid has an inhibitory effect on Candida albicans, with an inhibition rate of 72.46%.

[0329] 3. As can be seen from the experimental results of groups 10-15 in Table 17, at pH 3.6, the solutions of 1.25% sodium propionate combined with six different concentrations of dicarboxylic or polycarboxylic acids (3.54% succinic acid, 4.02% malic acid, 4.50% tartaric acid, 3.50% maleic acid, 5.76% citric acid, and 3.50% fumaric acid) all showed an inhibition rate of <25% against Candida albicans.

[0330] In conclusion, it is evident that the combination of adipic acid and sodium propionate has a synergistic antibacterial effect against Candida albicans.

[0331] Experimental Example Sixteen

[0332] Following the methods outlined in Appendix C of GB15979-2002 "Hygienic Standard for Disposable Sanitary Products", the inhibitory effects of citric acid, malic acid, and succinic acid on Candida albicans ATCC10231 were investigated using a basic antibacterial solution composed of "1.46% (w / w) adipic acid + 0.16% (w / w) sodium benzoate + 0.62% (w / w) propionic acid + 0.35% (w / w) phenylethanol". The solution was left to act for 20 minutes. All percentage concentrations of the components were expressed as weight percentages (w / w), and the pH of the basic antibacterial solution was 3.6. The experimental results are shown in Table 18.

[0333] Table 18 Effects of citric acid, malic acid, and succinic acid on antibacterial activity

[0334]

[0335] The results show:

[0336] 1. The basic antibacterial solution has an antibacterial effect against Candida albicans, with an inhibition rate of 53.77%.

[0337] 2. The basic antibacterial solution, with the addition of 1.00% citric acid, 0.70% malic acid, and 0.61% succinic acid, respectively, showed antibacterial rates of 49.25%, 54.77%, and 53.27% against Candida albicans.

[0338] In conclusion, it is evident that citric acid, malic acid, and succinic acid have no effect on the inhibitory effect of the basic antibacterial solution composed of "1.46% adipic acid, 0.16% sodium benzoate, 0.62% propionic acid, and 0.35% phenylethanol" on Candida albicans.

[0339] In vitro experiment 17

[0340] Following the methods outlined in Appendix C of GB15979-2002 "Hygienic Standard for Disposable Sanitary Products", the inhibition rates of different component combinations on Candida albicans ATCC 10231 were studied after 20 minutes of contact with the solution. All component concentrations are expressed as weight percentages (w / w), and the pH value was 3.8. The experimental results are shown in Table 19.

[0341] Table 19. Antibacterial effects of different solution combinations on Candida albicans ATCC 10231

[0342]

[0343]

[0344] The results show:

[0345] 1. As can be seen from the experimental results of groups 1-9 in Table 19, at pH 3.8, the inhibition rates of seven different concentrations of fatty acids (1.32% butyric acid, 0.70% valeric acid, 0.20% hexanoic acid, 0.12% heptanoic acid, 0.03% octanoic acid, 0.0075% nonanoic acid, and 0.005% decanoic acid) and two different concentrations of dicarboxylic acids (1.50% adipic acid and 2.00% pimelic acid) against Candida albicans were all <35% when used alone.

[0346] 2. As can be seen from the experimental results of groups 10-16 in Table 19, at pH 3.8, solutions of seven different concentrations of fatty acids (1.32% butyric acid, 0.70% valeric acid, 0.20% hexanoic acid, 0.12% heptanoic acid, 0.03% octanoic acid, 0.0075% nonanoic acid, and 0.005% decanoic acid) combined with 1.50% adipic acid have an inhibitory effect or a strong inhibitory effect on Candida albicans, with an inhibition rate between 50% and 90% or >90%.

[0347] 3. As can be seen from the experimental results of groups 17-23 in Table 19, at pH 3.8, solutions of seven different concentrations of fatty acids (1.32% butyric acid, 0.70% valeric acid, 0.20% hexanoic acid, 0.12% heptanoic acid, 0.03% octanoic acid, 0.0075% nonanoic acid, and 0.005% decanoic acid) combined with 2.00% pimelic acid have an inhibitory effect or a strong inhibitory effect on Candida albicans, with an inhibition rate between 50% and 90% or >90%.

[0348] In summary, it can be seen that at pH 3.8, solutions of seven different concentrations of fatty acids (1.32% butyric acid, 0.70% valeric acid, 0.20% hexanoic acid, 0.12% heptanoic acid, 0.03% octanoic acid, 0.0075% nonanoic acid, and 0.005% decanoic acid) combined with 1.50% adipic acid and 2.00% pimelic acid exhibit synergistic antibacterial effects against Candida albicans, all of which enhance the antibacterial effect.

[0349] In vitro experiment 18

[0350] Following the methods outlined in Appendix C of GB15979-2002 "Hygienic Standard for Disposable Sanitary Products", the inhibition rates of different component combinations on Escherichia coli ATCC25922, Staphylococcus aureus ATCC6538, and Candida albicans ATCC10231 were studied after 20 minutes of contact with the solution. All component concentrations are expressed as weight percentages (w / w), and the pH value was 3.8. The experimental results are shown in Table 20.

[0351] Table 20. Antibacterial effects of different solutions on Escherichia coli, Staphylococcus aureus, and Candida albicans.

[0352]

[0353] As shown in Table 20, at pH 3.8, nine different concentrations of fatty acids (3.00% butyric acid, 0.45% hexanoic acid, 0.30% heptanoic acid, 0.05% octanoic acid, 0.03% nonanoic acid, 0.008% decanoic acid, 0.006% undecanoic acid, 0.006% undecenoic acid, and 0.006% lauric acid) and 5.00% pimelic acid, when used individually, exhibited strong or 50% inhibitory effects against Candida albicans, with inhibition rates ranging from 50% to 90% or exceeding 90%. They also showed strong inhibitory effects against Escherichia coli and Staphylococcus aureus, with inhibition rates of 100.00% in both cases.

[0354] In vitro experiment 19

[0355] Following the methods outlined in Appendix C of GB 15979-2002 "Hygienic Standard for Disposable Sanitary Products," the inhibitory effects of aqueous solutions containing different component combinations on *Candida albicans* ATCC10231 were studied after 20 minutes of treatment. All component concentrations were expressed as weight percentages (w / w), and the pH value was 3.8. The experimental results are shown in Table 21.

[0356] Table 21. Antibacterial effects of different solutions on Candida albicans ATCC 10231

[0357] No. Propionic acid (%) Pimelic acid (%) Cinnamic alcohol (%) Sodium benzoate (%) Bacteriostatic rate (%) 1 2.00 1.50 -- 0.20 41.25 2 2.00 1.50 0.03 0.20 72.15 3 2.00 1.50 0.05 0.20 84.54 4 2.00 1.50 0.08 0.20 95.21

[0358] The results show:

[0359] 1. As can be seen from the experimental results of Group 1 in Table 21, at pH 3.8, the solution of 1.50% pimelic acid, 0.20% sodium benzoate and 2.00% propionic acid has an inhibition rate of 41.25% against Candida albicans.

[0360] 2. As can be seen from the experimental results of groups 2-4 in Table 21, at pH 3.8, the solution of 0.03-0.08% cinnamyl alcohol combined with "1.50% pimelic acid, 0.20% sodium benzoate, and 2.00% propionic acid" has an inhibitory effect on Candida albicans or a strong inhibitory effect, with an inhibition rate of 50%-90% or >90%.

[0361] In summary, 0.03-0.08% cinnamyl alcohol significantly affects the inhibitory effect of the solution containing the combination of 1.50% pimelic acid, 0.20% sodium benzoate, and 2.00% propionic acid on Candida albicans, enhancing its antibacterial activity.

[0362] In vitro experiment 20

[0363] Following the methods outlined in Appendix C of GB 15979-2002 "Hygienic Standard for Disposable Sanitary Products," the inhibitory effects of aqueous solutions containing different component combinations on *Candida albicans* ATCC10231 were studied after 20 minutes of treatment. All component concentrations were expressed as weight percentages (w / w), and the pH value was 4.8. The experimental results are shown in Table 22.

[0364] Table 22 Antibacterial effects of different solutions on Candida albicans ATCC 10231

[0365] No. Propionic acid (%) Pimelic acid (%) Sodium benzoate (%) Bacteriostatic rate (%) 1 -- 5.00 -- 15.42 2 -- -- 1.18 15.92 3 0.10 -- -- 2.90 4 0.10 5.00 1.18 61.02

[0366] The results show:

[0367] 1. As can be seen from the experimental results of groups 1-3 in Table 22, at pH 4.8, the inhibition rates of 5.00% pimelic acid, 1.18% sodium benzoate, and 0.10% propionic acid against Candida albicans were all less than 20% when used alone.

[0368] 2. As can be seen from the experimental results of Group 4 in Table 22, at pH 4.8, the solution of "5.00% pimelic acid, 1.18% sodium benzoate, and 0.10% propionic acid" has an inhibitory effect on Candida albicans, with an inhibition rate of 61.02%.

[0369] In summary, at pH 4.8, the solution containing the three components "5.00% pimelic acid, 1.18% sodium benzoate, and 0.10% propionic acid" exhibits a synergistic antibacterial effect against Candida albicans, with enhanced antibacterial activity.

[0370] In vitro experiment 21

[0371] Following the methods outlined in Appendix C of GB 15979-2002 "Hygienic Standard for Disposable Sanitary Products," the inhibitory effects of aqueous solutions containing different component combinations on *Escherichia coli* ATCC25922 and *Staphylococcus aureus* ATCC6538 were studied after 20 minutes of treatment. All component concentrations were expressed as weight percentages (w / w), and the pH value was 4.0. The experimental results are shown in Table 23.

[0372] Table 23. Antibacterial effects of different solutions on Escherichia coli ATCC25922 and Staphylococcus aureus ATCC6538

[0373]

[0374] The results show:

[0375] 1. As can be seen from the experimental results of groups 1-4 in Table 23, at pH 4.0, solutions of 0.06% sodium benzoate combined with 0.30% phenylethanol, 0.50% propionic acid, 0.45% butyric acid, and 0.06% hexanoic acid have antibacterial effects against Escherichia coli and Staphylococcus aureus, with antibacterial rates all higher than 50%.

[0376] 2. As can be seen from the experimental results of groups 5-7 in Table 23, at pH 4.0, the solutions of 0.30% phenylethanol combined with 0.50% propionic acid, 0.45% butyric acid and 0.06% hexanoic acid have antibacterial effects on Escherichia coli and Staphylococcus aureus, with antibacterial rates all higher than 50%.

[0377] 3. As can be seen from the experimental results of groups 8-10 in Table 23, at pH 4.0, the solution of "0.045% sodium benzoate, 0.30% phenylethanol" combined with 0.35% propionic acid has an inhibitory effect on Escherichia coli and Staphylococcus aureus, with inhibition rates higher than 50%; the solutions of "0.045% sodium benzoate, 0.30% phenylethanol" combined with 0.30% butyric acid and 0.06% hexanoic acid respectively have strong inhibitory effects on Escherichia coli and Staphylococcus aureus, with inhibition rates higher than 90%.

[0378] 4. As can be seen from the experimental results of groups 11-13 in Table 23, at pH 4.0, the solutions of "1.50% adipic acid, 0.045% sodium benzoate, and 0.30% phenylethanol" combined with three different concentrations of fatty acids (0.35% propionic acid, 0.30% butyric acid, and 0.06% hexanoic acid) have a strong antibacterial effect on Escherichia coli, with inhibition rates all above 90%, and also have an antibacterial effect on Staphylococcus aureus, with inhibition rates between 50% and 90%.

[0379] In vitro experiment 22

[0380] Following the methods outlined in Appendix C of GB 15979-2002 "Hygienic Standard for Disposable Sanitary Products," the inhibitory effects of aqueous solutions containing different component combinations on *Candida albicans* ATCC10231 were studied after 20 minutes of treatment. All component concentrations are expressed as weight percentages (w / w). The experimental results are shown in Table 24.

[0381] Table 24. Antibacterial effects of different solutions on Candida albicans ATCC 10231

[0382]

[0383] As shown in the experimental results of groups 1-3 in Table 24, the combined solution of "0.06% citric acid, 1.17% adipic acid, 0.20% propionic acid, 0.60% butyric acid, 0.20% sodium benzoate, and 0.40% phenylethanol" has an inhibitory effect on Candida albicans at pH values ​​of 4.0 and 4.2, with inhibition rates of 86.56% and 66.74%, respectively. At pH value of 4.4, the inhibition rate of the above combined solution on Candida albicans is 37.61%.

[0384] In conclusion, it is evident that the lower the pH value of the solution containing the combination of "0.06% citric acid, 1.17% adipic acid, 0.20% propionic acid, 0.60% butyric acid, 0.20% sodium benzoate, and 0.40% phenylethanol", the stronger the antibacterial effect against Candida albicans.

[0385] In vitro experiment 23

[0386] Following the methods outlined in Appendix C of GB 15979-2002 "Hygienic Standard for Disposable Sanitary Products," the inhibitory effects of aqueous solutions containing different component combinations on *Candida albicans* ATCC10231 were studied after 20 minutes of treatment. All component concentrations were expressed as weight percentages (w / w), and the solution pH was 3.86. The experimental results are shown in Table 25.

[0387] Table 25. Antibacterial effects of different solutions on Candida albicans ATCC 10231

[0388]

[0389] The results show:

[0390] 1. As can be seen from the experimental results of Group 1 in Table 25, at pH 3.86, the solution of the combination of "1.46% adipic acid, 0.20% malic acid, 0.12% sodium benzoate, 0.20% propionic acid, 0.45% butyric acid, 0.30% phenylethanol, and 1.80% palaginose" has an inhibitory effect on Candida albicans, with an inhibition rate of 75.14%.

[0391] 2. As can be seen from the experimental results in Group 2 of Table 25, at pH 3.86, the solution containing the combination of "1.46% adipic acid, 0.20% malic acid, 0.12% sodium benzoate, 0.20% propionic acid, 0.45% butyric acid, 0.30% phenylethanol, 1.80% palaginose, and 0.04% puerarin" has an inhibitory effect on Candida albicans, with an inhibition rate of 78.45%.

[0392] 3. As can be seen from the experimental results of Group 3 in Table 25, at pH 3.86, the solution containing the combination of "1.46% adipic acid, 0.20% malic acid, 0.12% sodium benzoate, 0.20% propionic acid, 0.45% butyric acid, 0.30% phenylethanol, 1.80% palaginose, and 0.06% puerarin" has an inhibitory effect on Candida albicans, with an inhibition rate of 76.24%.

[0393] In conclusion, at a solution pH of 3.86, the 0.04% and 0.06% puerarin components in the solution had no effect on the inhibitory effect of Candida albicans, and the antibacterial effect was not weakened.

[0394] Understandably, other estrogenic substances, such as diethylstilbestrol, hexanestilbestrol, estradiol, estrone, estriol, soliestrol, ethinylestradiol, ethinylestradiol cyclopentyl ether, ethinylestradiol methyl ether, proestrene, and other phytoestrogens, such as daidzein, genistein, daidzein, puerarin, estradiol, genistein, valerol, apigenin, genistein, genistein, gentianin, coumarin, gentianin, resveratrol, linolenic acid, and lignans, have similar properties and mechanisms of action to puerarin. Therefore, it can be inferred that the aforementioned estrogenic substances and phytoestrogens will not significantly weaken the inhibitory effect of the composition on Candida albicans.

[0395] In vitro experiments 24

[0396] Following the methods outlined in Appendix C of GB 15979-2002 "Hygienic Standard for Disposable Sanitary Products," the inhibitory effects of aqueous solutions containing different component combinations on *Candida albicans* ATCC10231 were studied after 20 minutes of treatment. All component concentrations were expressed as weight percentages (w / w), and the pH value was 4.0. The experimental results are shown in Table 26.

[0397] Table 26. Antibacterial effects of different solutions on Candida albicans ATCC 10231

[0398]

[0399] The results show:

[0400] Comparing the experimental results of Group 1 and Group 2 in Table 26, it can be seen that at pH 4.0, 0.55% glutamic acid has no effect on the inhibitory effect of the solution of "0.14% malic acid, 1.46% adipic acid, 0.20% sodium benzoate, 1.67% propionic acid, and 0.40% phenylethanol" on Candida albicans.

[0401] Understandably, other suitable amino acids, such as glutamine, L-aspartic acid, asparagine, leucine, isoleucine, phenylalanine, valine, proline, and threonine, have similar properties and mechanisms of action to glutamic acid. Therefore, it can be inferred that the aforementioned amino acids will not affect the inhibitory effect of the composition on Candida albicans.

[0402] In vitro experiment 25

[0403] Following the methods outlined in Appendix C of GB 15979-2002 "Hygienic Standard for Disposable Sanitary Products," the inhibitory effects of aqueous solutions containing different component combinations on *Escherichia coli* ATCC25922 and *Staphylococcus aureus* ATCC6538 were studied after 20 minutes of treatment. All component concentrations were expressed as weight percentages (w / w), and the pH value was 3.8. The experimental results are shown in Table 27.

[0404] Table 27. Antibacterial effects of different solutions on Escherichia coli ATCC25922 and Staphylococcus aureus ATCC6538

[0405]

[0406] The results show:

[0407] 1. As can be seen from the experimental results of groups 1-4 in Table 27, at pH 3.8, solutions of 1.75% adipic acid combined with 1.50% propionic acid, 1.30% butyric acid, 0.50% valeric acid, and 0.20% hexanoic acid have strong antibacterial effects against Escherichia coli, with an inhibition rate of 100.00% in all cases. They also have antibacterial effects or strong antibacterial effects against Staphylococcus aureus, with an inhibition rate between 50% and 90% or >90%.

[0408] 2. As can be seen from the experimental results of groups 5-8 in Table 27, at pH 3.8, the solutions of 0.03% cinnamyl alcohol and 1.75% adipic acid combined with 1.50% propionic acid, 1.30% butyric acid, 0.50% valeric acid, and 0.20% hexanoic acid respectively have strong antibacterial effects against Escherichia coli and Staphylococcus aureus, with an inhibition rate of 100.00% for both.

[0409] 3. As can be seen from the experimental results of groups 9-12 in Table 27, at pH 3.8, solutions of 0.03% cinnamic acid and 1.75% adipic acid combined with 1.50% propionic acid, 1.30% butyric acid, 0.50% valeric acid, and 0.20% hexanoic acid, respectively, have strong antibacterial effects against Escherichia coli and Staphylococcus aureus, with an inhibition rate of 100.00% for all of them.

[0410] In vitro experiments 26

[0411] The antibacterial efficacy test method and result judgment criteria in Part IV of the 2020 edition of the Pharmacopoeia of the People's Republic of China were basically followed. The antibacterial effects of each antibacterial agent in the composition against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans and Aspergillus niger were studied. The experimental results are shown in Table 28.

[0412] Table 28 Compositions 1 Antibacterial efficacy test

[0413]

[0414] Note:

[0415] 1. The composition contains: 1.50% (w / w) adipic acid, 0.14% (w / w) sodium benzoate, 0.32% (w / w) phenylethyl alcohol, 0.54% (w / w) propionic acid, 0.20% (w / w) hexanoic acid, 0.20% (w / w) paraffinose, 0.60% (w / w) maltose, 0.0005% (w / w) rose essential oil, and 2.15% (w / w) xanthan gum.

[0416] 2. The difference between the lg value of the bacterial count measured at each time interval and the lg value of the bacterial count inoculated into 1 ml (g) of test sample.

[0417] 3. No increase means that the number of experimental bacteria increased by no more than 0.5lg from the previous measurement time.

[0418] As can be seen from the experimental results in Table 28, at pH 4.2, the lg value of the decrease in bacterial concentration after 14 days compared to day 0 was 5 for each experimental bacteria, and the lg value of the decrease after 28 days compared to day 14 days did not increase, which meets the requirements; it can be seen that the composition at pH 4.2 in this experiment has a preservative effect.

[0419] It is worth noting that even if the experimental conditions and methods are exactly the same, the results of in vitro antibacterial experiments, such as the antibacterial rate, may still differ when the experiment is repeated due to experimental errors. However, this difference is reasonable and understandable to those skilled in the art. Therefore, if there is any inconsistency between the in vitro experimental data in this disclosure and the data in prior applications, the data in this disclosure shall prevail.

[0420] In vivo experiment 1

[0421] Three groups of gels containing different components were administered vaginally to cynomolgus monkeys once daily at a dose of 0.5 ml for 5 consecutive days. Vaginal swabs were collected to measure pH value and smears were stained and examined under a microscope to observe the effects of the gels on the pH value and vaginal flora of the cynomolgus monkeys. The experimental results are shown in Table 29.

[0422] Table 29 Effects of antibacterial gels containing different components on vaginal acidity and flora in cynomolgus monkeys.

[0423]

[0424] Note:

[0425] Group B gels contain 2.50% (w / w) maltose, 0.20% (w / w) isomaltulose, 0.16% (w / w) sodium benzoate, 0.60% (w / w) sodium propionate, 0.35% (w / w) phenylethyl alcohol, 1.00% (w / w) citric acid, 1.168% (w / w) adipic acid, and 2.15% (w / w) xanthan gum, adjusted to pH 3.6.

[0426] 2: Group C gel contains 2.50% (w / w) maltose, 0.20% (w / w) isomaltulose, 0.16% (w / w) sodium benzoate, 0.60% (w / w) sodium propionate, 0.35% (w / w) phenylethyl alcohol, 0.61% (w / w) succinic acid, 1.168% (w / w) adipic acid, and 2.15% (w / w) xanthan gum, adjusted to pH 3.6.

[0427] 3: Group 2 gels contain 1.15% (w / w) sodium propionate, 0.45% (w / w) phenylethyl alcohol, 0.20% (w / w) sodium benzoate, 1.50% (w / w) maltose, 1.00% (w / w) citric acid, and 2.15% (w / w) xanthan gum, adjusted to pH 3.6.

[0428] 4. The Nugent score is determined by microscopic examination of vaginal secretion smears after Gram staining, based on the staining, morphology, and quantity of bacteria, as detailed below:

[0429] ≥7 points, vaginal bacteria are mainly Gram-negative bacilli and / or Gram-negative cocci and Gram-positive cocci, with no or very few large Gram-positive bacilli;

[0430] A score of 4-6 indicates that vaginal bacteria are mainly Gram-negative bacilli and / or Gram-negative cocci and / or Gram-positive cocci, with fewer large Gram-positive bacilli.

[0431] A score of 0-3 indicates normal vaginal flora, with large Gram-positive bacilli predominating.

[0432] The results show:

[0433] 1. As can be seen from the experimental results of Group B in Table 29: A gel containing "2.50% (w / w) maltose, 0.20% (w / w) isomaltulose, 0.16% (w / w) sodium benzoate, 0.60% (w / w) sodium propionate, 0.35% (w / w) phenylethanol, 1.00% (w / w) citric acid, 1.168% (w / w) adipic acid, and 2.15% (w / w) xanthan gum" with a pH of 3.6, after 5 applications, resulted in a decrease in the pH of vaginal secretions of all 3 cynomolgus monkeys to 3.8, and a decrease in the Nugent score of vaginal flora to 0-3 points.

[0434] 2. As can be seen from the experimental results of Group C in Table 29: A gel containing "2.50% (w / w) maltose, 0.20% (w / w) isomaltulose, 0.16% (w / w) sodium benzoate, 0.60% (w / w) sodium propionate, 0.35% (w / w) phenylethanol, 0.61% (w / w) succinic acid, 1.168% (w / w) adipic acid, and 2.15% (w / w) xanthan gum" with a pH of 3.6, after 5 applications, the pH of the vaginal secretions of all 3 cynomolgus monkeys decreased to 3.8, and the Nugent score of the vaginal flora decreased to 0-3 points in 1 of the 3 monkeys and 4-6 points in 2 of the 3 monkeys.

[0435] 3. As can be seen from the experimental results of Group 2 in Table 29: With a pH value of 3.6, a gel containing "1.15% (w / w) sodium propionate, 0.45% (w / w) phenylethanol, 0.20% (w / w) sodium benzoate, 1.50% (w / w) maltose, 1.00% (w / w) citric acid, and 2.15% (w / w) xanthan gum" was administered 5 times. In 3 of the 5 cynomolgus monkeys, the pH value of vaginal secretions decreased to 3.8, 1 decreased to 4.4, and 1 was due to menstrual shedding; the Nugent score of vaginal flora decreased to 0-3 in 3 of the 3 monkeys, 1 was still >7, and 1 was due to menstrual shedding.

[0436] In summary, all three gels with a pH of 3.6 in this experiment showed that they all inhibited abnormal vaginal flora, restored vaginal acidity, and restored vaginal lactobacilli. Among the gels containing adipic acid and the two gels containing citric acid and succinic acid respectively (groups B and C), group B was more effective than group C and the second gel without adipic acid. The second gel without adipic acid had the weakest effect in inhibiting abnormal vaginal flora, restoring vaginal acidity, and restoring vaginal lactobacilli among the three gels.

[0437] In vivo experiment 2

[0438] Three groups of gels containing different components were administered intravaginally to rhesus monkeys once daily at a dose of 0.5 ml for 5 consecutive days. Vaginal secretions were collected to measure pH and smears were stained and examined under a microscope to observe the effects of the gels on the pH value and vaginal flora of the rhesus monkeys' vaginal secretions. The experimental results are shown in Table 30.

[0439] Table 30 Effects of antibacterial gels containing different components on vaginal acidity and flora in rhesus monkeys.

[0440]

[0441]

[0442] Note:

[0443] 1: Group A gel contains 2.00% (w / w) isomaltulose, 0.12% (w / w) sodium benzoate, 0.60% (w / w) butyric acid, 1.31% (w / w) adipic acid, 0.30% (w / w) phenylethyl alcohol, 0.35% (w / w) malic acid, and 2.15% (w / w) xanthan gum, adjusted to pH 4.1.

[0444] 2: Group B gel contains 2.00% (w / w) isomaltulose, 0.12% (w / w) sodium benzoate, 0.60% (w / w) butyric acid, 0.0010% (w / w) decanoic acid, 1.31% (w / w) adipic acid, 0.30% (w / w) phenylethyl alcohol, 0.35% (w / w) malic acid, and 2.15% (w / w) xanthan gum, adjusted to pH 4.1.

[0445] 3: Group C gel contains 2.00% (w / w) isomaltulose, 0.12% (w / w) sodium benzoate, 0.60% (w / w) butyric acid, 0.0015% (w / w) decanoic acid, 1.31% (w / w) adipic acid, 0.30% (w / w) phenylethyl alcohol, 0.35% (w / w) malic acid, and 2.15% (w / w) xanthan gum, adjusted to pH 4.1.

[0446] 4: Note 4 of Experiment 1 in vivo

[0447] The results show:

[0448] 1. The results of Group A show that: a gel containing "1.31% (w / w) adipic acid, 0.35% (w / w) malic acid, 0.30% (w / w) phenylethanol, 0.12% (w / w) sodium benzoate, 0.60% (w / w) butyric acid", 2.00% (w / w) isomaltulose, and 2.15% (w / w) xanthan gum" was administered 5 times. In 3 out of 4 rhesus monkeys, the pH of their vaginal secretions decreased to 3.8, and the Nugent score of their vaginal flora decreased to 0-3. In the remaining 1 rhesus monkey, the pH of its vaginal secretions remained at 5.4, and the Nugent score of its vaginal flora decreased to 4-6.

[0449] 2. The results of Group B show that: a gel with a pH of 4.1 containing "1.31% (w / w) adipic acid, 0.35% (w / w) malic acid, 0.30% (w / w) phenylethanol, 0.12% (w / w) sodium benzoate, 0.60% (w / w) butyric acid, 0.0010% (w / w) decanoic acid", 2.00% (w / w) isomaltulose, and 2.15% (w / w) xanthan gum" was used 5 times. In 3 out of 5 rhesus monkeys, the pH of their vaginal secretions decreased to 3.8, and the Nugent score of their vaginal flora decreased to 0-3 points; in 1 monkey, the pH of their vaginal secretions decreased to 4.1, and the Nugent score of their vaginal flora decreased to 4-6 points; and in 1 monkey, the pH of their vaginal secretions remained at 5.4, and the Nugent score of their vaginal flora decreased to 4-6 points.

[0450] 3. The results of Group C show that: a gel with a pH of 4.1 containing "1.31% (w / w) adipic acid, 0.35% (w / w) malic acid, 0.30% (w / w) phenylethanol, 0.12% (w / w) sodium benzoate, 0.60% (w / w) butyric acid, 0.0015% (w / w) decanoic acid", 2.0% (w / w) isomaltulose, and 2.15% (w / w) xanthan gum" was used 5 times. In one of the two rhesus monkeys, the pH of the vaginal secretions decreased to 3.8 and the Nugent score of the vaginal flora decreased to 0-3. In the other monkey, the pH of the vaginal secretions decreased to 4.1 and the Nugent score of the vaginal flora decreased to 4-6.

[0451] In summary, the three gels containing 0.60% (w / w) butyric acid, 0.00125% (w / w) decanoic acid, and 0.0015% (w / w) decanoic acid in this experiment have the effects of inhibiting abnormal vaginal flora, regulating vaginal flora, restoring vaginal lactobacilli, and restoring normal vaginal acidity.

[0452] In vivo experiment 3

[0453] Five groups of gels containing different components were administered vaginally to cynomolgus monkeys once daily at a dose of 0.5 ml for five consecutive days. Vaginal swabs were collected to measure pH values ​​and smears were stained and examined under a microscope to observe the effects of the gels on the pH value and vaginal flora of the cynomolgus monkeys. The experimental results are shown in Table 31.

[0454] Table 31 Effects of antibacterial gels containing different components on vaginal acidity and flora in cynomolgus monkeys.

[0455]

[0456] Note:

[0457] 1: Group 1 gels contain 0.14% (w / w) sodium benzoate, 0.54% (w / w) propionic acid, 1.46% (w / w) adipic acid, 0.30% (w / w) phenylethyl alcohol, 0.35% (w / w) malic acid, and 2.15% (w / w) xanthan gum, adjusted to pH 3.8.

[0458] 2: Group 2 gels contain 2.00% (w / w) maltose, 0.14% (w / w) sodium benzoate, 0.54% (w / w) propionic acid, 1.46% (w / w) adipic acid, 0.30% (w / w) phenylethyl alcohol, 0.35% (w / w) malic acid, and 2.15% (w / w) xanthan gum, adjusted to pH 3.8.

[0459] 3: Group 3 gels contain 2.0% (w / w) isomaltulose, 0.14% (w / w) sodium benzoate, 0.54% (w / w) propionic acid, 1.46% (w / w) adipic acid, 0.30% (w / w) phenylethyl alcohol, 0.35% (w / w) malic acid, and 2.15% (w / w) xanthan gum, adjusted to pH 3.8.

[0460] 4: Group 4 gels contain 2.00% (w / w) isomaltulose, 0.12% (w / w) sodium benzoate, 0.38% (w / w) propionic acid, 1.31% (w / w) adipic acid, 0.0015% (w / w) decanoic acid, 0.30% (w / w) phenylethyl alcohol, 0.35% (w / w) malic acid, and 2.15% (w / w) xanthan gum, adjusted to pH 3.9.

[0461] 5: Group 5 gel contains 2.00% (w / w) isomaltulose, 0.12% (w / w) sodium benzoate, 0.38% (w / w) propionic acid, 1.31% (w / w) adipic acid, 0.01% (w / w) caprylic acid, 0.30% (w / w) phenylethyl alcohol, 0.35% (w / w) malic acid, and 2.15% (w / w) xanthan gum, adjusted to pH 3.9.

[0462] 6: Note 4 of Experiment 1 in vivo

[0463] The results show:

[0464] 1. As can be seen from the experimental results of Groups 1 to 3 in Table 31: Group 1 gel without sugar, Group 2 gel containing 2.00% (w / w) maltose, and Group 3 gel containing 2.00% (w / w) isomaltulose, are completely identical in other components except for the sugar component. The pH value of all three groups is 3.8, and they all contain "0.14% (w / w) sodium benzoate, 0.54% (w / w) propionic acid, 1.46% (w / w) adipic acid, 0.30% (w / w) phenylethanol, 0.35% (w / w) malic acid, and 2.15% (w / w) xanthan gum".

[0465] After three doses of medication, the pH value of vaginal secretions in all three groups decreased to 4.1 or below. In terms of vaginal flora Nugent scores, in the sugar-free group 1, two of the four cynomolgus monkeys decreased to 4-6 points, and two decreased to 0-3 points. In the maltose-containing group 2, both of the two cynomolgus monkeys decreased to 0-3 points. In the isomaltulose-containing group 3, two of the three cynomolgus monkeys decreased to 0-3 points, and one decreased to 4-6 points.

[0466] 2. As can be seen from the experimental results of Group 4 in Table 31: After five applications of a gel containing "2.00% (w / w) isomaltulose, 0.12% (w / w) sodium benzoate, 0.38% (w / w) propionic acid, 1.31% (w / w) adipic acid, 0.30% (w / w) phenylethanol, 0.35% (w / w) malic acid, 0.0015% (w / w) decanoic acid, and 2.15% (w / w) xanthan gum" with a pH of 3.9, the pH of the vaginal secretions of the two cynomolgus monkeys decreased to 3.8, and the Nugent score of the vaginal flora decreased to 0-3 points in one monkey and 4-6 points in the other monkey.

[0467] 3. As can be seen from the experimental results of Group 5 in Table 31: After three applications of a gel containing "2.00% (w / w) isomaltulose, 0.12% (w / w) sodium benzoate, 0.38% (w / w) propionic acid, 1.31% (w / w) adipic acid, 0.30% (w / w) phenylethanol, 0.35% (w / w) malic acid, 0.01% (w / w) caprylic acid, and 2.15% (w / w) xanthan gum" with a pH of 3.9, the pH of the vaginal secretions of the two cynomolgus monkeys decreased to 3.8, and the Nugent score of the vaginal flora decreased to 0-3.

[0468] In conclusion:

[0469] 1. The gel in this experiment, with a pH of 3.8 and containing a combination of 1.46% (w / w) adipic acid, 0.35% (w / w) malic acid, 0.54% (w / w) propionic acid, 0.30% (w / w) phenylethanol, and 0.14% (w / w) sodium benzoate, but without sugar, exhibited the effects of inhibiting abnormal vaginal flora, restoring vaginal acidity, and restoring vaginal lactobacilli, as shown in the results of Group 1. However, the gels in Groups 2 and 3, which further contained maltose or isomaltulose, showed a faster and stronger effect in restoring vaginal lactobacilli than the sugar-free gel in Group 1, as shown in the results of Groups 2 and 3.

[0470] 2. The gels in this experiment, with a pH of 3.9 and containing "1.31% (w / w) adipic acid, 0.35% (w / w) malic acid, 0.38% (w / w) propionic acid, 0.30% (w / w) phenylethanol, 0.12% (w / w) sodium benzoate, and 2.0% (w / w) isomaltulose", as well as gels containing 0.0015% (w / w) decanoic acid and 0.01% (w / w) caprylic acid respectively, have the effects of inhibiting abnormal vaginal flora, restoring vaginal acidity, and restoring vaginal lactobacilli, as shown in the results of experiments group 4 and group 5.

[0471] In vivo experiment four

[0472] Three groups of gels containing different components were administered vaginally to cynomolgus monkeys once daily at a dose of 0.5 ml for 5 consecutive days. Vaginal swabs were collected to measure pH value and smears were stained and examined under a microscope to observe the effects of the gels on the pH value and vaginal flora of the cynomolgus monkeys' vaginal secretions. The experimental results are shown in Table 32.

[0473] Table 32 Effects of antibacterial gels containing different components on vaginal acidity and flora in cynomolgus monkeys.

[0474]

[0475] Note:

[0476] 1: Group 1 gel contains 2.00% (w / w) isomaltulose, 0.12% (w / w) sodium benzoate, 0.38% (w / w) propionic acid, 1.31% (w / w) adipic acid, 0.04% (w / w) heptanoic acid, 0.30% (w / w) phenylethyl alcohol, 0.35% (w / w) malic acid, and 2.15% (w / w) xanthan gum, adjusted to pH 3.9.

[0477] Note 2: Group 2 gels contain 2.00% (w / w) isomaltulose, 0.12% (w / w) sodium benzoate, 0.38% (w / w) propionic acid, 1.31% (w / w) adipic acid, 0.10% (w / w) hexanoic acid, 0.30% (w / w) phenylethyl alcohol, 0.35% (w / w) malic acid, and 2.15% (w / w) xanthan gum, adjusted to pH 3.9.

[0478] Note 3: Group 3 gels contain 2.00% (w / w) isomaltulose, 0.12% (w / w) sodium benzoate, 0.38% (w / w) propionic acid, 1.31% (w / w) adipic acid, 0.20% (w / w) valeric acid, 0.30% (w / w) phenylethyl alcohol, 0.35% (w / w) malic acid, and 2.15% (w / w) xanthan gum, adjusted to pH 3.9.

[0479] Note 4: Same as Note 4 in in vivo experiment 1

[0480] The results show:

[0481] 1. As can be seen from the experimental results of Group 1 in Table 32: A gel containing "2.00% (w / w) isomaltulose, 0.12% (w / w) sodium benzoate, 0.38% (w / w) propionic acid, 1.31% (w / w) adipic acid, 0.30% (w / w) phenylethanol, 0.35% (w / w) malic acid, 0.04% (w / w) heptanoic acid, and 2.15% (w / w) xanthan gum" with a pH of 3.9, after 5 applications, reduced the pH of vaginal secretions in cynomolgus monkeys to 3.8 and reduced the Nugent score of vaginal flora to 0-3 points.

[0482] 2. As can be seen from the experimental results of Group 2 in Table 32: After five applications of a gel containing "2.00% (w / w) isomaltulose, 0.12% (w / w) sodium benzoate, 0.38% (w / w) propionic acid, 1.31% (w / w) adipic acid, 0.30% (w / w) phenylethanol, 0.35% (w / w) malic acid, 0.10% (w / w) hexanoic acid, and 2.15% (w / w) xanthan gum" with a pH of 3.9, the pH of the vaginal secretions of the two cynomolgus monkeys decreased to 4.1 or below, and the Nugent score of the vaginal flora decreased to 0-3 points.

[0483] 3. As can be seen from the experimental results of Group 3 in Table 32: With a pH of 3.9, a gel containing "2.00% (w / w) isomaltulose, 0.12% (w / w) sodium benzoate, 0.38% (w / w) propionic acid, 1.31% (w / w) adipic acid, 0.30% (w / w) phenylethanol, 0.35% (w / w) malic acid, 0.20% (w / w) valeric acid, and 2.15% (w / w) xanthan gum" was administered 5 times. The pH of the vaginal secretions of the two cynomolgus monkeys remained at 5.4. The Nugent score of the vaginal flora decreased to 0-3 points in one cynomolgus monkey and 4-6 points in the other.

[0484] In summary, the three gels tested in this experiment—one with a pH of 3.9 containing 2.00% (w / w) isomaltulose, 0.12% (w / w) sodium benzoate, 0.38% (w / w) propionic acid, 1.31% (w / w) adipic acid, 0.30% (w / w) phenylethanol, and 0.35% (w / w) malic acid, and the other containing 0.04% (w / w) heptanoic acid, 0.10% (w / w) hexanoic acid, 0.20% (w / w) valeric acid, and 2.15% (w / w) xanthan gum—all exhibited the effect of inhibiting abnormal vaginal flora and restoring vaginal lactobacilli. The other two gels, containing 0.04% (w / w) heptanoic acid and 0.10% (w / w) hexanoic acid respectively, also had the effect of restoring vaginal acidity.

[0485] In vivo experiment five

[0486] Six gels containing different components were administered vaginally to cynomolgus monkeys once daily at a dose of 0.5 ml for five consecutive days. Vaginal swabs were collected to measure pH and smears were stained and examined under a microscope to observe the effects of the gels on the pH value and vaginal flora of the cynomolgus monkeys' vaginal secretions. The experimental results are shown in Table 33.

[0487] Table 33 Effects of antibacterial gels containing different components on vaginal acidity and flora in cynomolgus monkeys.

[0488]

[0489]

[0490] Note:

[0491] 1: Group 1 gels contain 0.10% (w / w) hexanoic acid, 1.50% (w / w) adipic acid, 2.00% (w / w) maltose, and 2.15% (w / w) xanthan gum, adjusted to pH 3.1.

[0492] 2: Group 2 gels contain 2.00% (w / w) propionic acid, 0.30% (w / w) cinnamyl alcohol, 0.60% (w / w) succinic acid, 2.00% (w / w) maltose, and 2.15% (w / w) xanthan gum, adjusted to pH 3.8.

[0493] 3: Group 3 gels contain 0.02% (w / w) caprylic acid, 0.25% (w / w) benzoic acid, 1.00% (w / w) citric acid, 2.00% (w / w) maltose, and 2.15% (w / w) xanthan gum, adjusted to pH 3.8.

[0494] 4: Group 4 gels contain 0.20% (w / w) benzoic acid, 0.25% (w / w) benzyl alcohol, 0.001% (w / w) undecanoic acid, 1.00% (w / w) malic acid, 2.00% (w / w) maltose, and 2.15% (w / w) xanthan gum, adjusted to pH 3.80.

[0495] 5: Group 5 gels contain 0.20% (w / w) benzoic acid, 0.50% (w / w) propionic acid, 1.50% (w / w) adipic acid, 2.00% (w / w) maltose, and 2.15% (w / w) xanthan gum, adjusted to pH 3.8.

[0496] 6: Group 6 gels contain 1.00% (w / w) pimecrolic acid, 0.60% (w / w) phenylethanol, 1.25% (w / w) butyric acid, 2.00% (w / w) maltose, and 2.15% (w / w) xanthan gum, adjusted to pH 3.8.

[0497] 7: Note 4 of Experiment 1 in vivo

[0498] The results show:

[0499] 1. As can be seen from the experimental results of Group 1 in Table 33: When the pH value was 3.1 and the gel containing "0.10% (w / w) hexanoic acid, 1.50% (w / w) adipic acid, 2.00% (w / w) maltose, and 2.15% (w / w) xanthan gum" was administered 5 times, the experiment was terminated in 1 of the 3 cynomolgus monkeys due to menstruation. The pH value of the vaginal secretions of the other 2 monkeys remained at 5.4 in one monkey and dropped to 3.8 in the other monkey. The Nugent score of the vaginal flora dropped to 4-6 points in one monkey and to 0-3 points in the other monkey.

[0500] 2. As can be seen from the experimental results of Group 2 in Table 33: A gel containing "2.00% (w / w) propionic acid, 0.30% (w / w) cinnamyl alcohol, 0.60% (w / w) succinic acid, 2.00% (w / w) maltose, and 2.15% (w / w) xanthan gum" with a pH of 3.8, after 5 applications, the pH of vaginal secretions in 1 of the 2 cynomolgus monkeys decreased to 4.1, while the pH remained at 5.4. The Nugent score of vaginal flora decreased to 4-6 in 1 monkey and 0-3 in 2 monkeys.

[0501] 3. As can be seen from the experimental results of Group 3 in Table 33: With a pH value of 3.8 and containing "0.02% (w / w) caprylic acid, 0.25% (w / w) benzoic acid, 1.00% (w / w) citric acid, 2.00% (w / w) maltose, and 2.15% (w / w) xanthan gum", after 5 doses, the pH value of the vaginal secretions of the two cynomolgus monkeys decreased to 3.8 in one monkey and 4.1 in the other; the Nugent score of the vaginal flora of both monkeys decreased to 0-3 points.

[0502] 4. As can be seen from the experimental results of Group 4 in Table 33: With a pH value of 3.8, after five administrations of a drug containing "0.20% (w / w) benzoic acid, 0.25% (w / w) benzyl alcohol, 0.001% (w / w) undecanoic acid, 1.00% (w / w) malic acid, 2.00% (w / w) maltose, and 2.15% (w / w) xanthan gum", the pH value of vaginal secretions in the two cynomolgus monkeys decreased to 4.6 in one and 3.8 in the other; the Nugent score of vaginal flora decreased to 4-6 in one and 0-3 in the other.

[0503] 5. As can be seen from the experimental results of Group 5 in Table 33: With a pH value of 3.8 and containing "0.20% (w / w) benzoic acid, 0.50% (w / w) propionic acid, 1.50% (w / w) adipic acid, 2.00% (w / w) maltose, and 2.15% (w / w) xanthan gum", after 5 treatments, the pH value of vaginal secretions in 1 of the cynomolgus monkeys decreased to 4.6 and that of 1 monkey decreased to 3.8; the Nugent score of vaginal flora decreased to 4-6 in 1 monkey and to 0-3 in 1 monkey.

[0504] 6. As can be seen from the experimental results of Group 6 in Table 33: With a pH value of 3.8 and containing "1.00% (w / w) pimelic acid, 0.60% (w / w) phenylethanol, 1.25% (w / w) butyric acid, 2.00% (w / w) maltose, and 2.15% (w / w) xanthan gum", after 5 doses, the pH value of vaginal secretions in 1 of the cynomolgus monkeys decreased to 3.8 and that of 1 monkey decreased to 4.1; the Nugent score of vaginal flora decreased to 0-3 in 1 monkey and to 4-6 in 1 monkey.

[0505] In summary, it can be seen that the above six gel compositions have the effects of inhibiting abnormal vaginal flora, restoring vaginal acidity, and restoring vaginal lactobacilli.

[0506] In vivo experiment six

[0507] A gel containing adipic acid and fumaric acid was administered vaginally to cynomolgus monkeys once daily for 5 consecutive days at a dose of 0.5 ml. Vaginal swabs were collected to measure pH and smears were stained and examined under a microscope to observe the effects of the gel on the pH value and vaginal flora of the cynomolgus monkeys. The experimental results are shown in Table 34.

[0508] Table 34 Effects of gels containing adipic acid and fumaric acid on vaginal acidity and flora in cynomolgus monkeys.

[0509]

[0510] Note:

[0511] 1: Group 1 gels contain 1.50% (w / w) fumaric acid, 1.00% (w / w) propionic acid, 0.08% (w / w) cinnamic acid, 0.25% (w / w) phenylethyl alcohol, 1.40% (w / w) maltose, and 2.15% (w / w) xanthan gum, adjusted to pH 3.8.

[0512] 2: Group 2 gels contain 1.50% (w / w) adipic acid, 1.00% (w / w) propionic acid, 0.08% (w / w) cinnamic acid, 0.25% (w / w) phenylethyl alcohol, 1.40% (w / w) maltose, and 2.15% (w / w) xanthan gum, adjusted to pH 3.8.

[0513] 3: Note 4 of Experiment 1 in vivo

[0514] The results show:

[0515] 1. As can be seen from the experimental results of Group 1 in Table 34: A gel containing "1.50% (w / w) fumaric acid, 1.00% (w / w) propionic acid, 0.08% (w / w) cinnamic acid, 0.25% (w / w) phenylethanol, 1.40% (w / w) maltose, and 2.15% (w / w) xanthan gum" with a pH of 3.8, administered 5 times, still resulted in a vaginal secretion pH of 5.4 in two cynomolgus monkeys. The Nugent score of the vaginal flora remained >7 in one monkey, while it decreased to 4-6 in the other.

[0516] 2. As can be seen from the experimental results of Group 2 in Table 34: After five administrations of a gel containing "1.50% (w / w) adipic acid, 1.00% (w / w) propionic acid, 0.08% (w / w) cinnamic acid, 0.25% (w / w) phenylethanol, 1.40% (w / w) maltose, and 2.15% (w / w) xanthan gum" with a pH of 3.8, the pH of the vaginal secretions of the two cynomolgus monkeys decreased to 4.1, and the Nugent score of the vaginal flora decreased to 0-3.

[0517] In conclusion, the gel containing 1.50% (w / w) adipic acid in this experiment has the effects of inhibiting abnormal vaginal flora, restoring vaginal lactobacilli, and restoring vaginal acidity.

[0518] Clinical observation 1

[0519] Ten patients with bacterial vaginosis (BV) and five healthy volunteers were included in this study. Gel A was administered vaginally once daily at a dose of 4.5g for five consecutive days. On day 3 of treatment (V1) and three days after treatment (V2), vaginal swabs were collected to measure pH and smears were stained and examined under a microscope to observe the effects of the gel on the pH of vaginal secretions and vaginal flora. The experimental results are shown in Table 35.

[0520] Table 35 Effects of Gel A on Vaginal Acidity and Microbiota in BV Patients and Healthy Volunteers

[0521]

[0522]

[0523] Note 1: Gel A contains 1.46% (w / w) adipic acid, 0.70% (w / w) sodium propionate, 0.14% (w / w) sodium benzoate, 0.32% (w / w) phenylethyl alcohol, 1.00% (w / w) citric acid, 1.60% (w / w) maltose, 0.20% (w / w) paraffinose, 0.0005% (w / w) rose essential oil, and 2.15% (w / w) xanthan gum, adjusted to pH 3.70.

[0524] Note 2: pH values ​​were measured using a pH standard range colorimetric card. The colorimetric card has two ranges: 3.8-4.1 indicates normal, and 4.6-5.4 indicates abnormal.

[0525] Note 3: Same as Note 7 in in vivo experiment 1

[0526] The results show:

[0527] 1. As shown in Table 35, the experimental results of BV patients showed that: a gel containing "1.46% (w / w) adipic acid, 0.70% (w / w) sodium propionate, 0.14% (w / w) sodium benzoate, 0.32% (w / w) phenylethanol, 1.00% (w / w) citric acid, 1.60% (w / w) maltose, 0.20% (w / w) palaginose, 0.0005% (w / w) rose essential oil, and 2.15% (w / w) xanthan gum" with a pH of 3.70, after 3 applications, resulted in a pH decrease of 3.8-4.1 in 7 out of 10 BV patients, a decrease in vaginal flora Nugent score of 3 or below in 3 cases, and a decrease of 4-6 in 4 cases.

[0528] After 5 doses of medication, the medication was stopped for 3 days for observation. Among the 10 BV patients, the pH value of 9 patients dropped to 3.8-4.1 and the vaginal flora Nugent score dropped to below 3. The pH value of 1 patient remained at 4.6-5.4 and the vaginal flora Nugent score dropped to 6.

[0529] 2. As shown in Table 35, the experimental results of healthy volunteers showed that a gel with a pH of 3.70 containing "1.46% (w / w) adipic acid, 0.70% (w / w) sodium propionate, 0.14% (w / w) sodium benzoate, 0.32% (w / w) phenylethanol, 1.00% (w / w) citric acid, 1.60% (w / w) maltose, 0.20% (w / w) palaginose, 0.0005% (w / w) rose essential oil, and 2.15% (w / w) xanthan gum" had no effect on the pH of vaginal secretions or vaginal flora in healthy volunteers after three applications.

[0530] After 5 doses of medication, the medication was stopped for 3 days for observation. It had no effect on the pH value and flora of vaginal secretions in healthy volunteers.

[0531] In summary, the gel containing 1.46% (w / w) adipic acid, 0.70% (w / w) sodium propionate, 0.14% (w / w) sodium benzoate, 0.32% (w / w) phenylethanol, 1.00% (w / w) citric acid, 1.60% (w / w) maltose, 0.20% (w / w) palaginose, 0.0005% (w / w) rose essential oil, and 2.15% (w / w) xanthan gum in the vagina of BV patients significantly reduced abnormal flora, significantly increased lactobacilli, and decreased pH. However, it had no effect on the pH or normal flora of normal vaginal secretions in healthy volunteers. This suggests that the gel has the function of inhibiting abnormal vaginal flora, restoring and / or maintaining vaginal lactobacilli, and restoring and / or maintaining normal vaginal acidity.

[0532] References:

[0533] 1. Fang Liang (ed.), Pharmaceutics, People's Medical Publishing House, 8th edition, 2016, pp. 243-252;

[0534] 2. Fang Liang (ed.), Pharmaceutics, People's Medical Publishing House, 8th edition, 2016, pp. 211-228;

[0535] 3. Fang Liang (ed.), Pharmaceutics, People's Medical Publishing House, 8th edition, 2016, pp. 234-237;

[0536] 4. Fang Liang (ed.), Pharmaceutics, People's Medical Publishing House, 8th edition, 2016, pp. 280-284.

[0537] Although the invention has been described with reference to exemplary embodiments, it should be understood that the invention is not limited to the disclosed exemplary embodiments. Various adjustments or changes may be made to the exemplary embodiments described in this specification without departing from the scope or spirit of the invention. The scope of the claims should be interpreted in the broadest possible sense to cover all modifications and equivalent structures and functions.

Claims

1. A bacteriostatic composition, characterized in that, The bacteriostatic composition comprises the following components: (1) one or more fatty acids and / or salts thereof, the fatty acid being selected from the group consisting of acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, undecylic acid, undecenoic acid, and lauric acid, the total content of component (1) being in the range of 0.10-3.0% (w / w) based on the fatty acid; (2) one or more dibasic acids and / or salts thereof, the dibasic acid being selected from the group consisting of glutaric acid, adipic acid, and pimelic acid, the total content of component (2) being in the range of 0.10-3.5% (w / w) based on the dibasic acid; (3) one or more aromatic alcohols, the aromatic alcohol being selected from the group consisting of benzyl alcohol, phenethyl alcohol, phenoxyethanol, and cinnamic alcohol, the total content of component (3) being in the range of 0.03-0.70% (w / w); (4) one or more aromatic acids and / or salts thereof, the aromatic acid being selected from the group consisting of benzoic acid, p-hydroxybenzoic acid, p-methoxybenzoic acid, salicylic acid, cinnamic acid, gentisic acid, and caffeic acid, the total content of component (4) being in the range of 0.03-0.50% (w / w) based on the aromatic acid; The bacteriostatic composition is in the form selected from the group consisting of an aqueous solution, a water-soluble gel, a foam, a spray, an ointment, a powder, a film, a capsule, a suppository, and a tablet.

2. The bacteriostatic composition according to claim 1, characterized in that, The bacteriostatic composition further comprises component (5): one or more dibasic and / or polybasic acids selected from the group consisting of malic acid, citric acid, succinic acid, tartaric acid, maleic acid, and isocitric acid, and / or salts thereof, the total content being in the range of 0.10-2.50% (w / w).

3. The bacteriostatic composition of claim 1, wherein The bacteriostatic composition further comprises one or more sugars selected from the group consisting of glucose, fructose, mannose, galactose, maltose, isomaltose, sucrose, isomaltulose, lactose, lactulose, trehalose, cellobiose, melibiose, gentiobiose, raffinose, stachyose, melezitose, isomaltotriose, isomaltotetraose, isomaltopentaose, oligogentiobiose, raffinose, panose, malto-oligosaccharides, isomaltulose-oligosaccharides, fructo-oligosaccharides, glucomannan, galacto-oligosaccharides, dextrin, starch, and glycogen, the total content being in the range of 0.01-20.00% (w / w).

4. The bacteriostatic composition of claim 1, wherein The bacteriostatic composition further comprises one or more amino acids and / or salts thereof selected from the group consisting of L-glutamic acid, glutamine, L-aspartic acid, asparagine, leucine, isoleucine, phenylalanine, valine, proline, and threonine, the total content being in the range of 0.10-6.00% (w / w).

5. The bacteriostatic composition of claim 1, wherein The bacteriostatic composition further comprises one or more monoterpenes or sesquiterpenes selected from the group consisting of citronellol, linalool, geraniol, nerol, eucalyptol, terpineol, carvesol, menthol, and lavandulol.

6. The bacteriostatic composition of claim 1, wherein The bacteriostatic composition further comprises one or more plant aromatic oil substances selected from the group consisting of rose essential oil, clove oil, sage oil, lavender oil, mint oil, wormwood leaf oil, eucalyptus leaf oil, sassafras oil, litsea cubeba essential oil, cinnamon essential oil, bay leaf oil, and thyme oil.

7. The bacteriostatic composition of claim 1, wherein The bacteriostatic composition further comprises one or more vitamins selected from the group consisting of vitamin A, vitamin C, vitamin D, and vitamin E.

8. The bacteriostatic composition of claim 1, wherein, The bacteriostatic composition further comprises one or more substances selected from the group consisting of dehydroacetic acid, sodium dehydroacetate, sorbic acid, potassium sorbate, sodium sorbate, natamycin, ushinsun, ambrettolide, cinnamaldehyde, adonitol, chlorogenic acid, 1,2-pentanediol, 1,2-hexanediol, 1,6-hexanediol, 1,2-octanediol, 1,2-decanediol, p-hydroxyacetophenone, 2,4-dihydroxyacetophenone, methyl paraben, ethyl paraben, propyl paraben, lysozyme, glycerol monocaprylate, glycerol monocaprate, and glycerol monolaurate.

9. The bacteriostatic composition of claim 1, wherein, The bacteriostatic composition further comprises one or more antibacterial drugs selected from the group consisting of metronidazole, tinidazole, ornidazole, gentamicin, tobramycin, amikacin, sisomicin, netilmicin, ciprofloxacin, ofloxacin, levofloxacin, nitrofurazone, nitrofural oxime, furacillin, furazolidone, furantoin, silver sulfadiazine, sodium sulfacetamide, clotrimazole, fluconazole, miconazole, ketoconazole, naftifine, terbinafine, amphotericin B, nystatin, zymonistatin, and natamycin.

10. The bacteriostatic composition of claim 1, wherein The bacteriostatic composition is an aqueous solution, a water-soluble gel, a foam, a spray, and an ointment having a pH in the range of 3.1 to 4.

8.

11. The bacteriostatic composition of claim 1, wherein The bacteriostatic composition is a therapeutic product, or an effective component thereof, or a preservative thereof, wherein the therapeutic product is in one of the following forms: a pharmaceutical product, a disinfectant, an antibacterial agent, a bacteriostatic agent, a skin-mucous surface microbicide, a microecological regulator, a microenvironment regulator, a microbial regulator, a single-use medical product, or in the form of a component of a medical device, a pharmaceutical device, and a sterilized device.

12. The bacteriostatic composition of claim 11, wherein, The medical device includes a vaginal device.

13. The bacteriostatic composition of claim 11, wherein, The microbial regulator includes a flora regulator.

14. The bacteriostatic composition of claim 1, wherein, The bacteriostatic composition is a non-therapeutic product, or an effective component thereof, or a preservative thereof, wherein the non-therapeutic product is in one of the following forms: a health care product, a sanitary product, a personal care product, a cosmetic product, a cleaning product, a daily product, a microecological care product, an odor-removing agent, a lubricant, a moisturizer, a lotion, a cleanser, a maintenance agent, an anti-itching agent, a freshener.

15. The bacteriostatic composition according to claim 14, wherein The sanitary product includes a single-use sanitary product, a sanitary napkin, a sanitary pad, and a sanitary tampon.

16. The bacteriostatic composition of claim 1, wherein, The bacteriostatic composition is a vaginal bacteriostatic composition comprising the following components: (1) one or more fatty acids selected from the group consisting of acetic acid, propionic acid, butyric acid, valeric acid, caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, undecylic acid, undecylenic acid, and lauric acid, the total content of component (1) being in the range of 0.10 to 2.00% (w / w) as fatty acid; (2) one or more dibasic acids selected from the group consisting of glutaric acid, adipic acid, and pimelic acid, the total content of component (2) being in the range of 0.50 to 2.50% (w / w) as dibasic acid; (3) one or more aromatic alcohols selected from the group consisting of benzyl alcohol, phenyl ethyl alcohol, phenoxy ethanol, and cinnamic alcohol, the total content of component (3) being in the range of 0.05 to 0.60% (w / w); (4) one or more aromatic acids selected from the group consisting of benzoic acid, p-hydroxy benzoic acid, p-methoxy benzoic acid, salicylic acid, cinnamic acid, gentisic acid, and caffeic acid, and / or salts thereof, the total content of component (4) being in the range of 0.05 to 0.25% (w / w) as aromatic acid; the dosage form of the vaginal bacteriostatic composition is selected from the group consisting of an aqueous solution, a water-soluble gel, a foam, a spray, an ointment, a powder, a film, a capsule, a suppository, and a tablet.

17. A method of inhibiting unwanted microorganisms, characterized by, The method is a non-disease diagnosis and treatment purpose method, and the harmful microorganism includes Candida albicans, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Gardnerella vaginalis, Prevotella, Mobiluncus, and Aspergillus niger.

18. The method of claim 17, wherein, 19. Use of a combination of a fatty acid and / or a salt thereof and a dibasic acid and / or a salt thereof in the manufacture of a vaginal bacteriostatic composition for regulating vaginal flora, characterized in that, (1) the fatty acid is selected from the group consisting of propionic acid, acetic propionic acid, butyric acid, valeric acid, caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, undecylic acid, undecylenic acid, and lauric acid, the total content of the fatty acid and / or a salt thereof being in the range of 0.10 to 2.00% (w / w) as fatty acid; (2) the dibasic acid is selected from the group consisting of glutaric acid, adipic acid, and pimelic acid, the total content of the dibasic acid and / or a salt thereof being in the range of 0.50 to 2.50% (w / w) as dibasic acid; wherein the dosage form of the vaginal bacteriostatic composition is selected from the group consisting of an aqueous solution, a water-soluble gel, a foam, a spray, an ointment, a powder, a film, a capsule, a suppository, and a tablet; the regulating of the vaginal flora includes at least one of inhibiting abnormal vaginal flora, restoring and / or maintaining lactobacilli in the vagina. wherein the total content of the fatty acid and / or a salt thereof is 0.10 to 1.50% (w / w) as fatty acid; and wherein the dibasic acid and / or a salt thereof is 0.50 to 1.50% (w / w) of adipic acid and / or a salt thereof as adipic acid.

20. Use according to claim 19, characterized in that, ​ 21. Use according to claim 19, characterized in that, The use is a use of a combination of a fatty acid and / or a salt thereof and a dibasic acid and / or a salt thereof in the manufacture of a bacteriostatic composition for vagina for inhibiting abnormal vaginal flora, wherein the inhibiting abnormal vaginal flora comprises inhibiting one or more bacteria selected from the group consisting of Staphylococcus, Streptococcus, Candida albicans, Gardnerella vaginalis, Escherichia coli, Veillonella, Prevotella, Mobiluncus.

22. The use according to claim 19, characterized in that, The bacteriostatic composition for vagina further comprises one or more aromatic alcohols selected from the group consisting of benzyl alcohol, 2,4-dichlorobenzyl alcohol, phenethyl alcohol, phenoxyethyl alcohol, and cinnamic alcohol, in a total content of 0.05-0.60% (w / w).

23. The use according to claim 19, characterized in that, The bacteriostatic composition for vagina further comprises one or more aromatic acids and / or salts thereof selected from the group consisting of benzoic acid, p-hydroxybenzoic acid, p-methoxybenzoic acid, salicylic acid, cinnamic acid, gentisic acid, and caffeic acid, in a total content of 0.05-0.25% (w / w) of the aromatic acid.

24. The use according to claim 19, characterized in that, The bacteriostatic composition for vagina further comprises one or more estrogens or phytoestrogens selected from the group consisting of dienestrol, diethylstilbestrol, estradiol, estrone, estriol, nylestriol, ethinylestradiol, ethinylestradiol cypionate, quinestrol, promestriene, daidzin, daidzein, glycitein, puerarin, coumestrol, formononetin, equol, apigenin, genistein, biochanin, calycosin, pterostilbene, secoisolaricirecinol, and lignan, in a total content of 0.001-1.00% (w / w).

25. The use according to claim 19, characterized in that, The bacteriostatic composition for vagina further comprises one or more sugars selected from the group consisting of glucose, fructose, mannose, galactose, maltose, isomaltose, sucrose, isomaltulose, lactose, lactulose, trehalose, cellobiose, melibiose, gentiobiose, raffinose, stachyose, melezitose, isomaltotriose, isomaltotetraose, isomaltopentaose, oligogentiobiose, raffinose, panose, malto-oligosaccharides, isomaltulose oligomers, fructo-oligosaccharides, glucomannan, galacto-oligosaccharides, dextrin, starch, and glycogen, in a total content of 0.01-20.00% (w / w).

26. The use according to claim 19, characterized in that, The bacteriostatic composition for vagina further comprises one or more amino acids and / or salts thereof selected from the group consisting of L-glutamic acid, glutamine, L-aspartic acid, asparagine, leucine, isoleucine, phenylalanine, valine, proline, and threonine, in a total content of 0.10-6.00% (w / w).

27. The use according to claim 19, characterized in that, The use is the use of a combination of a fatty acid and / or a salt thereof and a dibasic acid and / or a salt thereof in the manufacture of an antiseptic vaginal composition for restoring and / or maintaining the normal vaginal flora, and / or restoring and / or maintaining the normal microflora of the vagina, and / or restoring and / or maintaining the normal acidity of the vagina, and / or for the cleansing care of the vagina and / or vulva, and / or for reducing and / or eliminating itching, and / or pain, and / or dryness, and / or irritation, and / or sexual discomfort of the vagina and vulva, and / or for reducing and / or eliminating abnormal discharge, and / or abnormal odour of the vagina.

28. The use according to claim 19, characterized in that, The use is the use of a combination of a fatty acid and / or a salt thereof and a dibasic acid and / or a salt thereof in the manufacture of an antiseptic vaginal composition for preventing and / or treating a vaginal flora disorder, and / or bacterial vaginosis, and / or aerobic vaginitis, and / or cytolytic vaginosis, and / or vulvovaginal candidiasis, and / or atrophic vaginitis.

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