CN115515556A - Bacteriostatic composition and preparation method and application thereof - Google Patents
Bacteriostatic composition and preparation method and application thereof Download PDFInfo
- Publication number
- CN115515556A CN115515556A CN202180014214.2A CN202180014214A CN115515556A CN 115515556 A CN115515556 A CN 115515556A CN 202180014214 A CN202180014214 A CN 202180014214A CN 115515556 A CN115515556 A CN 115515556A
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- Prior art keywords
- acid
- bacteriostatic
- vaginal
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Abstract
The invention discloses a bacteriostatic composition and a preparation method and application thereof. The bacteriostatic composition 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 antibacterial composition can be made into water solution, water soluble gel, foam, spray, ointment, powder, pellicle, capsule, suppository or tablet, and can be used for inhibiting harmful microorganism, especially abnormal flora in vagina.
Description
The invention relates to a bacteriostatic composition, relates to a method for inhibiting harmful microorganisms, also relates to a method for regulating vaginal flora, and also relates to application of fatty acid and/or salt thereof in preparing the bacteriostatic composition for regulating vaginal flora, and relates to a preparation method of the bacteriostatic composition.
The skin and the mucous membrane of the human body are communicated with the outside, are easy to be infected with various germs and can be further developed into the germs on the skin and/or the mucous membrane for permanent planting and infection or carrying and spreading the germs. The antibacterial product is used for cleaning the skin and/or the mucous membrane part, so that the germ load of the skin and/or the mucous membrane part can be effectively reduced, even the germs can be killed, and the antibacterial product is helpful for preventing germ infection and transmission.
In order to prevent deterioration of various personal care products such as skin care products, cosmetics, bath products, hair washing products, etc., and various products for medical use, drugs, etc., due to microbial contamination during storage and use, it is necessary to inhibit the growth of microorganisms, and even to kill contaminating microorganisms, such as mold, yeast, escherichia coli, pseudomonas aeruginosa, staphylococcus aureus, etc.
Especially on the surface of human vaginal mucosa, a large number of microorganisms such as bacteria and fungi inhabit. Under the healthy state, the bacteria in the vagina of women mainly comprise lactobacillus, which metabolizes glycogen to produce acid in epithelial cells of the vaginal mucosa, keeps the pH value of the vagina within the range of 3.5-4.5, produces substances such as hydrogen peroxide, bacteriocin and the like, has inhibition effect on pathogenic bacteria and conditioned pathogenic bacteria, and is beneficial bacteria in the vagina, or is called as 'normal vaginal flora'.
The vagina also inhabits gardnerella vaginalis, prevotella, curvulus mobilis, escherichia coli, staphylococcus, candida and the like, and when the quantity is small, the vagina is not pathogenic, and when the quantity is large, substances such as harmful metabolites, toxins and the like can be generated, so that the human body is subjected to pathological changes and diseases, and the vagina is called as 'conditioned pathogen'. Among staphylococcus, staphylococcus aureus has strong pathogenicity and is representative; the candida is representative, and the most candida albicans accounts for more than 70% of the total number of the infection of the candida vaginalis and/or the candida vulvae.
When the vaginal flora is abnormal and the number of lactobacilli is small, the number of conditional pathogenic bacteria such as gardnerella vaginalis is increased, and the resistance to pathogenic bacteria with strong toxicity and strong pathogenicity is also reduced, so that the risk of infectious diseases of the genital tract is increased, such as the risk of infectious diseases caused by gonococcus, trichomonas, chlamydia, mycoplasma, HIV, HPV and the like.
The treatment of vaginal microbial diseases is currently still predominantly antibacterial. Although antibacterial treatment can inhibit or kill pathogenic bacteria, beneficial lactobacilli are often inhibited or even killed, so that the vaginal infection resistance is reduced, and vaginal infection is repeated or delayed. How to protect beneficial bacteria in vagina during antibacterial treatment so as to improve the prevention and treatment effects of vaginal infection still remains a hot problem in medical research.
Therefore, the safe and effective bacteriostatic product is suitable for cleaning, sanitation and bacteriostasis of skin and mucous membrane parts of a human body, is suitable for the corrosion prevention of personal washing products such as bath products, skin care products, cosmetics and the like, is suitable for the corrosion prevention of products for medical use, medicines and the like, and can be used for inhibiting abnormal vaginal flora, recovering and/or maintaining lactobacillus in vagina, recovering and/or maintaining normal vaginal flora and recovering and/or maintaining normal vaginal microecology, thereby having strong practicability and great market demand.
The information in this background is only for the purpose of illustrating the general background of the invention and should not be taken as an acknowledgement or any form of suggestion that this information forms the prior art that is known to a person skilled in the art.
Disclosure of Invention
An object of the present invention is to provide a bacteriostatic composition.
It is another object of the present invention to provide a method for inhibiting harmful microorganisms.
It is yet another object of the present invention to provide a method of modulating vaginal flora comprising inhibiting abnormal vaginal flora, restoring and/or maintaining vaginal lactobacilli.
It is a further object of the present invention to provide the use of a fatty acid and/or a salt thereof for the preparation of a bacteriostatic composition for modulating vaginal flora.
Still another object of the present invention is to provide a method for preparing a bacteriostatic composition.
The invention provides a bacteriostatic composition, which comprises the following components:
(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, caprylic acid, nonanoic acid, capric acid, undecanoic acid, undecylenic acid, and lauric acid, preferably from propionic acid, butyric acid, caproic acid, caprylic acid, decanoic acid, and undecanoic acid, and/or salts thereof, the total content of component (1) in terms of fatty acids being in the range of 0.001-3.00% (w/w);
(2) One or more dibasic acids selected from the group consisting of glutaric acid, adipic acid, and pimelic acid, preferably adipic acid, and the total content of component (2) in terms of dibasic acid is in the range of 0.05-5.00% (w/w);
(3) One or more aromatic alcohols selected from the group consisting of benzyl alcohol, 2,4-dichlorobenzyl alcohol, phenethyl alcohol, phenoxyethanol, and cinnamyl alcohol, preferably from the group consisting of phenethyl alcohol, cinnamyl alcohol, the total content of component (3) being in the range of 0.03-1.00% (w/w);
(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 from the group consisting of benzoic acid, cinnamic acid and p-hydroxybenzoic acid, the total content of component (4) in terms of aromatic acids being in the range of 0.03-1.00% (w/w);
the bacteriostatic composition adopts one of the following formulations: aqueous solutions, water-soluble gels, foams, sprays, ointments, powders, films, capsules, suppositories, and tablets, preferably aqueous solutions, water-soluble gels, foams, sprays, and ointments.
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), based on fatty acids; and/or the total content of the one or more dibasic acids and/or salts thereof is preferably in the range of 0.10 to 3.50% (w/w), more preferably in the range of 0.50 to 2.50% (w/w), most preferably in the range of 0.50 to 1.50% (w/w), based on the dibasic acid; and/or the total content of the 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 the 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), based on the aromatic acid.
In some embodiments, the bacteriostatic composition further comprises 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, preferably one or more dibasic and/or polybasic acids selected from malic acid, citric acid, and succinic acid, and/or salts thereof, in a total amount ranging from 0.10-2.50% (w/w). The acid and/or the salt thereof has a buffering effect, can enhance the pH stability of the bacteriostatic composition disclosed by the invention, and further enhances the regulating effect of the bacteriostatic composition disclosed by the invention on the pH value of human skin and/or mucous membrane parts.
In some embodiments, the bacteriostatic composition optionally contains one or more monosaccharides and/or oligosaccharides and/or polysaccharides in a total content ranging from 0.01-20.00% (w/w) selected from the group consisting of: glucose, fructose, mannose, galactose, maltose, isomaltose, sucrose, isomaltulose, lactose, lactulose, trehalose, cellobiose, melibiose, gentiobiose, kestose, nystose, kestose, kestopentaose, isomaltotriose, isomaltopentaose, gentiooligosaccharide, raffinose, panose, maltooligosaccharides, isomaltooligosaccharide, fructooligosaccharides, glucomannan, galactooligosaccharides, dextrins, starch, and glycogen; preferably isomaltulose, lactose, lactulose, maltose, isomaltose, trehalose, glycogen, or mixtures thereof in a total content in the range of 0.10-2.00% (w/w). The sugar-containing antibacterial composition disclosed by the invention can inhibit candida, staphylococcus aureus, escherichia coli, pseudomonas aeruginosa, gardnerella vaginalis, prevotella, campylobacter mobilis, aspergillus niger, abnormal flora of skin and/or mucous membrane parts and the like, can promote and/or maintain lactic acid bacteria of the skin and/or mucous membrane parts, promote and/or maintain acidity of the skin and/or mucous membrane parts, and can be used for preventing and/or treating reduction of lactic acid bacteria of the skin and/or mucous membrane parts and dysbacteriosis of the skin and/or mucous membrane parts, such as preventing and/or treating bacterial vaginosis, aerobic bacterial vaginitis, atrophic vaginitis, or auxiliary treatment of vaginitis, recovery after vaginitis treatment, treatment of genital tract infection and the like.
In some embodiments, the bacteriostatic composition optionally contains a total content of one or more amino acids and/or salts thereof selected from the group consisting of in the range of 0.10-6.00% (w/w): l-glutamic acid, glutamine, L-aspartic acid, asparagine, leucine, isoleucine, phenylalanine, valine, proline, and threonine, preferably glutamic acid and/or a salt thereof, and/or aspartic acid and/or a salt thereof, or a mixture thereof, in a total content in the range of 0.50 to 3.00% (w/w). The antibacterial composition containing the amino acid and/or the salt thereof can reduce acid production of lactic acid bacteria, so that the acidity of the skin and/or the mucous membrane is weakened, and the antibacterial composition is suitable for regulating the microenvironment of the skin and/or the mucous membrane, such as treating or assisting in treating cytolytic vaginosis, vaginal vulvocandidiasis and the like.
In some embodiments, the bacteriostatic composition optionally contains one or more monoterpene or sesquiterpene compounds in a total content ranging from 0.001-0.50% (w/w), including but not limited to: citronellol, linalool, geraniol, nerol, eucalyptol, terpineol, carveol, menthol, and lavandiol. The monoterpene or sesquiterpene compound can enhance the bacteriostatic action of the bacteriostatic composition and provide aromatic smell for the composition.
In some embodiments, the bacteriostatic composition optionally contains one or more plant aromatic oil-like substances in a total content ranging from 0.0001-0.05% (w/w), including but not limited to: rose essential oil, clove oil, thyme oil, lavender oil, peppermint oil, mugwort oil, eucalyptus oil, sassafras oil, litsea cubeba essential oil, cinnamon essential oil, bay leaf oil, and thyme oil. The plant aromatic oil can enhance the bacteriostatic action of the composition and can provide aromatic smell for the composition.
In some embodiments, the bacteriostatic composition optionally contains a total content of one or more vitamins selected from the group consisting of 0.001-0.50% (w/w): the vitamin substances can be high-purity vitamin substances or plant extracts containing the vitamin substances, have the effects of resisting oxidation, promoting the growth of skin cells, regulating the immune function, maintaining the integrity of mucous epithelium cells and the like, can enhance the stability of the antibacterial composition, or have a protective effect on human skin and/or mucous membranes.
In some embodiments, the bacteriostatic composition optionally contains one or more components selected from the group consisting of: dehydroacetic acid, sodium dehydroacetate, sorbic acid, potassium sorbate, sodium sorbate, natamycin, bergenin, tropolone, cinnamaldehyde, pseudolaric acid, chlorogenic acid, 1,2-pentanediol, 1,2-hexanediol, 1,6-hexanediol, 1,2-octanediol, 1,2-decanediol, p-hydroxyacetophenone, 2,4-dihydroxyacetophenone, methyl p-hydroxybenzoate, ethyl p-hydroxybenzoate, propyl p-hydroxybenzoate, lysozyme, glyceryl monocaprylate, glyceryl monocaprate, and glyceryl monolaurate. The components are used to further enhance the bacteriostatic or antibacterial effect of the bacteriostatic compositions of the present disclosure against candida, staphylococcus aureus, escherichia coli, pseudomonas aeruginosa, gardnerella vaginalis, prevotella, campylobacter, aspergillus niger, abnormal flora of skin and/or mucosal sites, etc., as well as other harmful microorganisms including but not limited to viruses such as HIV, HPV, etc.
In some embodiments, the bacteriostatic composition further comprises one or more antibacterial agents, 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, nifuroxime, nitrofurazone, furazolidone, nitrofurantoin, sulfonamides such as silver sulfadiazine, sulfacetamide sodium, pyrroles such as clotrimazole, fluconazole, miconazole, ketoconazole, allylamines such as naftifine, terbinafine, polyenes such as amphotericin B, nystatin, zymostatin, natamycin. Metronidazole, nifuratel, clotrimazole or mixtures thereof are preferred. The antibacterial composition containing the antibacterial drug is suitable for skin and/or mucosa, such as prevention and/or treatment of bacterial and/or fungal infection of skin, prevention and/or treatment of bacterial or fungal infection of oral mucosa, and prevention and/or treatment of bacterial vaginosis of vaginal mucosa, or aerobic bacterial vaginitis, or vaginal vulvocandidiasis, and the like.
In some embodiments, the bacteriostatic composition is in the form of one of the following: aqueous solutions, water-soluble gels, foams, sprays, and ointments; the pH value of the water solution, the water-soluble gel, the foam, the spray or the ointment ranges from 3.1 to 4.8, the pH value ranges from 3.6 to 4.6 preferably, and the pH value ranges from 3.8 to 4.4 more preferably.
In some embodiments, the bacteriostatic composition is a water-soluble gel further comprising one or more non-flowable, viscous, water-soluble colloidal matrices including, but not limited to, xanthan gum, carbomer, polycarbophil, dextran, glucomannan, tragacanth, methyl Cellulose (MC), carboxymethyl cellulose (CMC), hydroxyethyl cellulose (HEC), hydroxyethyl methyl cellulose (HEMC), hydroxypropyl methyl cellulose (HPMC), preferably xanthan gum, carbomer.
The bacteriostatic compositions of the present disclosure have inhibitory effects on harmful microorganisms including, but not limited to, candida, staphylococcus aureus, escherichia coli, pseudomonas aeruginosa, gardnerella vaginalis, prevotella, campylobacter, aspergillus niger, abnormal flora of skin and/or mucous membranes, other various pathogenic or conditionally pathogenic aerobic bacteria, facultative aerobic bacteria, anaerobic bacteria, molds, and viruses such as HPV, HIV, etc.
Therefore, the bacteriostatic composition disclosed by the invention 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 preserving personal care products such as various bath products, shampoo products, skin care products, cosmetics and the like, or preserving products for medical use, medicines and the like.
In some embodiments, the bacteriostatic compositions of the present disclosure may be used as therapeutic products, or effective components thereof, or preservatives thereof, including, but not limited to, pharmaceuticals, disinfectants, mucosal surface microbicides, antibacterial agents, bacteriostatic agents, microecological modulators, flora modulators, microenvironment modulators, microbial modulators, single use medical devices, and the like, or in the form of components of medical, pharmaceutical, disinfectant, and vaginal devices.
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 products, hygiene products, personal care products, cosmetics, disposable hygiene products, cleaning products, household products, micro-ecological care products, deodorants, lubricants, moisturizers, lotions, cleansers, maintenance agents, antipruritics, fresheners, or in the form of sanitary napkins, panty liners, and tampons.
In some embodiments, the bacteriostatic composition for vagina comprises the following components:
(1) One or more fatty acids and/or salts thereof selected from the group consisting of fatty acids in a total content in the range of 0.001-2.00% (w/w) based on fatty acids: acetic acid, glycolic acid, lactic acid, propionic acid, levulinic acid, butyric acid, valeric acid, caproic acid, enanthic 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 a mixture thereof in a total amount in the range of 0.001-1.50% (w/w), more preferably in a total amount in the range of 0.002-1.25% (w/w);
(2) One or more dibasic acids and/or salts thereof selected from the group consisting of: glutaric, adipic, pimelic, preferably adipic acid in a total content in the range of 0.50-1.50% (w/w);
(3) One or more aromatic alcohols selected from the group consisting of: benzyl alcohol, 2,4-dichlorobenzyl alcohol, phenethyl alcohol, phenoxyethanol, cinnamyl alcohol, preferably phenethyl alcohol, cinnamyl alcohol, or mixtures thereof, in a total content in the range of 0.08-0.50% (w/w);
(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 a mixture thereof in a total amount in the range of 0.08-0.20% (w/w).
The bacteriostatic composition for the vagina adopts one of the following formulations: aqueous solutions, water-soluble gels, foams, sprays, ointments, powders, films, capsules, suppositories, and tablets, preferably aqueous solutions, water-soluble gels, foams, sprays, and ointments.
In some embodiments, the bacteriostatic vaginal composition of the present disclosure further comprises one or more estrogens selected from the group consisting of: diethylstilbestrol, hexestrol, estradiol, estrone, estriol, nilestriol, ethinylestradiol cyclopentyl ether, ethinylestradiol methyl ether, and promestrene, with estriol and promestrene being preferred. The vaginal antibacterial composition containing the estrogen substances can promote the synthesis of glycogen by vaginal mucosa epithelial cells and promote the growth of beneficial lactobacillus, and is particularly suitable for menopause, postmenopause or postpartum.
In some embodiments, the bacteriostatic vaginal composition of the present disclosure further comprises one or more phytoestrogens selected from the group consisting of: daidzin, daidzein, glycitein, puerarin, coumestrol, genistein, equol, apigenin, genistin, genistein, biochanin, coumestrol, formononetin, resveratrol, secoisolariciresinol diglucoside, and lignan. The vaginal antibacterial composition containing the phytoestrogens can promote the synthesis of glycogen by vaginal mucosal epithelial cells and the growth of beneficial lactobacilli, and is particularly suitable for menopause, postmenopausal or postpartum.
The vaginal bacteriostatic composition disclosed by the invention can selectively contain water or different dosage form matrixes such as xanthan gum or carbomer and the like according to different application requirements, or selectively further contains one or more components as described above, such as dibasic acids such as malic acid, citric acid and succinic acid and/or salts thereof, polybasic acid and/or salts thereof, and/or antibacterial agents such as dehydroacetic acid and glyceryl monocaprylate, wherein the total content of the antibacterial agents is within the range of 0.10-2.50% (w/w), and/or carbohydrate substances such as isomaltulose, lactose and maltose, wherein the total content of the antibacterial agents is within the range of 0.01-20.00%, and/or amino acid substances such as glutamic acid and/or salts thereof, aspartic acid and/or salts thereof, and/or monoterpenes or compounds such as citronellol and linalool, wherein the total content of the antibacterial agents is within the range of 0.10-6.00% (w/w), and/or monoterpenes or essential oil substances such as citronellol and linalool, and/or essential oil substances such as clove and/05% (w/w) and/w essential oil, rose oil, vitamin A and vitamin C and vitamin A and/w) and/w are within the range of 0.001-0.50% and/w.
The bacteriostatic composition for the vagina has an inhibiting effect on abnormal flora in the vagina, has a restoring and/or maintaining and/or promoting effect on lactobacillus in the vagina, and can be used for restoring and/or maintaining normal flora of the vagina, restoring and/or maintaining normal microecology of the vagina and restoring and/or maintaining normal acidity of the vagina.
Thus, the vaginal bacteriostatic composition disclosed by the invention can be used for cleaning and nursing vagina and/or vulva, and/or relieving and/or eliminating vaginal vulvar pruritus, and/or pain, and/or dryness, and/or irritation, and/or dyspareunia, and/or relieving and/or eliminating abnormal leucorrhea, and/or abnormal leucorrhea and the like, and preventing and/or treating and/or assisting in treating vaginal dysbacteriosis, and/or bacterial vaginosis, and/or aerobic vaginitis, and/or cytolytic vaginosis, and/or vaginal vulvovaginal candidiasis, and/or atrophic vaginitis and the like.
The present invention also provides a method of inhibiting harmful microorganisms comprising the step of using a bacteriostatic composition, wherein the bacteriostatic composition comprises:
(1) One or more fatty acids and/or salts thereof 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, nonanoic acid, decanoic acid, undecanoic acid, undecylenic acid, and lauric acid, preferably from the group consisting of propionic acid, butyric acid, caproic acid, caprylic 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 fatty acids;
(2) One or more dibasic acids selected from the group consisting of glutaric acid, adipic acid, and pimelic acid, preferably adipic acid, and/or salts thereof; the total content of component (2) based on the dibasic acid is in the range of 0.05 to 5.00% (w/w), preferably in the range of 0.10 to 3.50% (w/w), more preferably in the range of 0.50 to 2.50% (w/w), most preferably in the range of 0.50 to 1.50% (w/w);
(3) One or more aromatic alcohols selected from the group consisting of benzyl alcohol, 2,4-dichlorobenzyl alcohol, phenethyl alcohol, phenoxyethanol, 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 to 1.00% (w/w), preferably in the range of 0.03 to 0.70% (w/w), more preferably in the range of 0.05 to 0.60% (w/w), most preferably in the range of 0.08 to 0.50% (w/w);
(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 from the group consisting of benzoic acid, cinnamic acid, and p-hydroxybenzoic acid; the total content of component (4) based on the aromatic acid is in the range of 0.03 to 1.00% (w/w), preferably in the range of 0.03 to 0.50% (w/w), more preferably in the range of 0.05 to 0.25% (w/w), and most preferably in the range of 0.08 to 0.20% (w/w).
Wherein the bacteriostatic composition adopts one of the following formulations: aqueous solutions, water-soluble gels, foams, sprays, ointments, powders, films, capsules, suppositories, and tablets, preferably aqueous solutions, water-soluble gels, foams, sprays, and ointments.
In some embodiments, the detrimental microorganisms in the methods of inhibiting detrimental microorganisms of the present disclosure include, but are not limited to, at least one of the following groups of microorganisms: candida, staphylococcus aureus, escherichia coli, pseudomonas aeruginosa, gardnerella vaginalis, prevotella, campylobacter, aspergillus niger, abnormal flora of the skin and/or mucous membranes, other various pathogenic or conditionally pathogenic aerobic bacteria, facultative aerobes, anaerobes, molds, as well as viruses HPV, HIV, and the like.
Thus, the bacteriostatic composition described in the method for inhibiting harmful microorganisms 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 preservation of personal care products such as various bath products, shampoo products, skin care products, cosmetics and the like, or for preservation of products for medical use, drugs and the like.
In some embodiments, the bacteriostatic composition in the method for inhibiting harmful microorganisms of the present disclosure is a therapeutic product, or an effective component thereof, or a preservative thereof, the therapeutic product includes, but is not limited to, drugs, disinfectants, antibacterial agents, bacteriostatic agents, mucosal surface microbicides, flora modulators, microecological modulators, microenvironment modulators, microbial modulators, disposable medical supplies, and the like, or is a component of medical devices, or pharmaceutical devices, or disinfecting devices, and vaginal devices.
In some embodiments, the bacteriostatic composition described in the methods of inhibiting harmful microorganisms of the present disclosure is a non-therapeutic product, or an effective component thereof, or a preservative thereof, including, but not limited to, health care products, personal care products, cosmetics, sanitary products, disposable sanitary products, cleaning products, household products, probiotics care products, odor removing agents, lubricants, humectants, lotions, cleansers, care agents, antipruritic agents, fresheners, and the like, or may be a component of a sanitary product or a cleaning care product, such as a sanitary napkin, or a pantiliner, or a tampon.
When the bacteriostatic composition described in the method for inhibiting harmful microorganisms of the present disclosure is used for preserving, the content of each component of the bacteriostatic composition described in the present disclosure, that is, the total content of the one or more fatty acids and/or salts thereof in terms of fatty acids, the total content of the one or more dibasic acids and/or salts thereof in terms of dibasic acids, the total content of the one or more aromatic alcohols, the total content of the one or more aromatic acids and/or salts thereof in terms of aromatic acids, and the like, contained in the products such as bath products, shampoo products, skin care products, cosmetics, or medicines, and other products for medical use, should all meet the range of the total content of the four components in the bacteriostatic composition described in the present disclosure.
The present invention also provides a method of modulating vaginal flora, wherein modulating vaginal flora comprises at least one of: lactobacillus to inhibit vaginal abnormal flora, restore and/or maintain the vagina, the method comprising the step of using a bacteriostatic vaginal composition, wherein the bacteriostatic vaginal composition contains one or more fatty acids and/or salts thereof in a total content in the range of 0.001-2.00% (w/w) calculated on fatty acids selected from the group consisting of butyric acid, valeric acid, caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, undecanoic acid, undecylenic acid, and lauric acid, preferably in a total content in the range of 0.001-1.50% (w/w), more preferably in a total content in the range of 0.002-1.25% (w/w) selected from the group consisting of butyric acid, caproic acid, caprylic acid, capric acid, undecanoic acid, or mixtures thereof.
Wherein the bacteriostatic composition for the vagina adopts one of the following formulations: aqueous solutions, water-soluble gels, foams, sprays, ointments, powders, films, capsules, suppositories, and tablets; aqueous solutions, water-soluble gels, foams, sprays, and ointments are preferred.
In some embodiments, the bacteriostatic vaginal composition for use in the method for modulating vaginal flora according to the present invention further comprises one or more dibasic acids and/or salts thereof in a total content of 0.50-2.50% (w/w) based on the dibasic acids, wherein the dibasic acids are selected from the group consisting of glutaric acid, adipic acid, and pimelic acid, preferably adipic acid in a total content of 0.50-1.50% (w/w), and/or salts thereof. The combination of the dibasic acid such as adipic acid and/or the salt thereof and the fatty acid such as butyric acid and/or the salt thereof disclosed by the invention can enhance the bacteriostatic action of the fatty acid and/or the salt thereof on candida albicans.
In some embodiments, the bacteriostatic vaginal composition for use in the method for modulating vaginal flora according to the present invention further comprises one or more aromatic alcohols selected from the group consisting of: benzyl alcohol, 2,4-dichlorobenzyl alcohol, phenethyl alcohol, phenoxyethanol, cinnamyl alcohol, preferably phenethyl alcohol, cinnamyl alcohol, or mixtures thereof, in a total content in the range of 0.08-0.50% (w/w). The combination of aromatic alcohols such as phenylethyl alcohol and the like and fatty acids such as butyric acid and/or salts thereof of the present disclosure can enhance the bacteriostatic action of the fatty acids and/or salts thereof on candida albicans, staphylococcus aureus, escherichia coli, abnormal vaginal flora and the like.
In some embodiments, the vaginal bacteriostatic composition used in the method for modulating vaginal flora of the present invention further comprises one or more aromatic acids and/or salts thereof in a total content ranging from 0.05 to 0.25% (w/w) based on aromatic acids 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 0.08 to 0.20% (w/w). The combination of the aromatic acid such as benzoic acid and/or a salt thereof and the fatty acid such as butyric acid and/or a salt thereof of the present disclosure can enhance the bacteriostatic action of the fatty acid and/or the salt thereof on candida albicans, staphylococcus aureus, escherichia coli, abnormal vaginal flora, and the like.
In some embodiments, the bacteriostatic vaginal composition for use in the method for modulating vaginal flora according to the present invention comprises: (1) One or more fatty acids and/or salts thereof in a total amount in the range of 0.001-2.00% (w/w) based on fatty acids 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 in a total amount in the range of 0.001-1.50% (w/w), more preferably in a total amount in the range of 0.002-1.25% (w/w) selected from the group consisting of butyric acid, caproic acid, caprylic acid, decanoic acid, undecanoic acid, or mixtures thereof; (2) One or more dibasic acids and/or salts thereof in a total content in the range of 0.50-2.50% (w/w) based on 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 in the range of 0.50-1.50% (w/w), and/or salts thereof; (3) One or more aromatic alcohols selected from the group consisting of: benzyl alcohol, 2,4-dichlorobenzyl alcohol, phenethyl alcohol, phenoxyethanol, cinnamyl alcohol, preferably phenethyl alcohol, cinnamyl alcohol, or mixtures thereof, in a total content in the range of 0.08-0.50% (w/w).
The combination of dibasic acid such as adipic acid and/or salt thereof, aromatic alcohol such as phenethyl alcohol and fatty acid such as butyric acid and/or salt thereof has synergistic bacteriostatic action on candida albicans, staphylococcus aureus, escherichia coli and the like, and has inhibitory action on abnormal vaginal flora.
In some embodiments, the bacteriostatic vaginal composition for use in the method for modulating vaginal flora of the present disclosure comprises: (1) One or more fatty acids and/or salts thereof in a total amount in the range of 0.001-2.00% (w/w) based on fatty acids 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 in a total amount in the range of 0.001-1.50% (w/w), more preferably in a total amount in the range of 0.002-1.25% (w/w) selected from the group consisting of butyric acid, caproic acid, caprylic acid, capric acid, undecanoic acid, or mixtures thereof, and/or salts thereof; (2) One or more dibasic acids and/or salts thereof in a total amount in the range of 0.50-2.50% (w/w) based on dibasic acid selected from the group consisting of glutaric acid, adipic acid, and pimelic acid, preferably adipic acid in a total amount in the range of 0.50-1.50% (w/w), and/or salts thereof; (3) One or more aromatic acids and/or salts thereof in a total content in the range of 0.05-0.25% (w/w) based on 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 mixtures thereof in a total content in the range of 0.08-0.20% (w/w), and/or salts thereof.
The combination of dibasic acid such as adipic acid and/or salt thereof, aromatic acid such as benzoic acid and/or salt thereof, and fatty acid such as butyric acid and/or salt thereof has a synergistic bacteriostatic action on candida albicans, staphylococcus aureus, escherichia coli and the like, and has an inhibitory action on abnormal vaginal flora.
In some embodiments, the bacteriostatic vaginal composition for use in the method for modulating vaginal flora of the present disclosure comprises: (1) One or more fatty acids and/or salts thereof in a total amount in the range of 0.001-2.00% (w/w) based on fatty acids 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 in a total amount in the range of 0.001-1.50% (w/w), more preferably in a total amount in the range of 0.002-1.25% (w/w) selected from the group consisting of butyric acid, caproic acid, caprylic acid, capric acid, undecanoic acid, or mixtures thereof, 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, preferably phenethyl alcohol, cinnamyl alcohol, or mixtures thereof, in a total content in the range of 0.08-0.50% (w/w); (3) One or more aromatic acids and/or salts thereof in a total content in the range of 0.05-0.25% (w/w) based on 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 mixtures thereof in a total content in the range of 0.08-0.20% (w/w), and/or salts thereof.
The combination of aromatic alcohol such as phenethyl alcohol, aromatic acid such as benzoic acid and/or salt thereof and fatty acid such as butyric acid and/or salt thereof has a synergistic bacteriostatic action on candida albicans, staphylococcus aureus, escherichia coli and the like, and has an inhibitory action on abnormal vaginal flora.
In some embodiments, the vaginal bacteriostatic composition of the methods of modulating vaginal flora of the present disclosure comprises: (1) One or more fatty acids and/or salts thereof in a total amount in the range of 0.001-2.00% (w/w) based on fatty acids 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 in a total amount in the range of 0.001-1.50% (w/w), more preferably in a total amount in the range of 0.002-1.25% (w/w) selected from the group consisting of butyric acid, caproic acid, caprylic acid, capric acid, undecanoic acid, or mixtures thereof, and/or salts thereof; (2) One or more dibasic acids and/or salts thereof in a total content in the range of 0.50-2.50% (w/w) based on 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 in the range of 0.50-1.50% (w/w), and/or salts thereof; (3) One or more aromatic alcohols selected from the group consisting of: benzyl alcohol, 2,4-dichlorobenzyl alcohol, phenethyl alcohol, phenoxyethanol, and cinnamyl alcohol, preferably phenethyl alcohol, cinnamyl alcohol, or a mixture thereof, in a total amount in the range of 0.08-0.50% (w/w); (4) One or more aromatic acids and/or salts thereof in a total amount in the range of 0.05-0.25% (w/w) based on aromatic acids selected from the group consisting of benzoic acid, p-hydroxybenzoic acid, p-methoxybenzoic acid, salicylic acid, cinnamic acid, gentisic acid and caffeic acid, preferably in a total amount in the range of 0.08-0.20% (w/w) of benzoic acid, cinnamic acid, p-hydroxybenzoic acid or mixtures thereof.
The combination of dibasic acid such as adipic acid and/or salt thereof, aromatic alcohol such as phenethyl alcohol, aromatic acid such as benzoic acid and/or salt thereof and fatty acid such as butyric acid and/or salt thereof has a synergistic bacteriostatic action on candida albicans, staphylococcus aureus, escherichia coli and the like, and has an inhibitory action on abnormal vaginal flora. The bacteriostatic composition is used for remarkably reducing abnormal flora and remarkably increasing lactobacillus in the vagina after being used for the vagina, and has the effects of inhibiting the abnormal flora in the vagina, restoring and/or maintaining and/or promoting the lactobacillus in the vagina and restoring and/or maintaining the normal acidity of the vagina.
In some embodiments, the bacteriostatic vaginal composition for use in the method for modulating vaginal flora according to the present disclosure further comprises one or more estrogens selected from the group consisting of: diethylstilbestrol, hexestrol, estradiol, estrone, estriol, nilestriol, ethinylestradiol cyclopentyl ether, ethinylestradiol methyl ether, and promestrene, with estriol and promestrene being preferred. The estrogen substances can promote epithelial cells of vaginal mucosa to synthesize glycogen and promote beneficial lactobacillus to grow, and the bacteriostatic composition containing the estrogen substances is particularly suitable for menopause, postmenopause or postpartum.
In some embodiments, the bacteriostatic vaginal composition for use in the method for modulating vaginal flora of the present disclosure further comprises one or more phytoestrogens in a total amount ranging from 0.001-1.00% (w/w): daidzin, daidzein, glycitein, puerarin, coumestrol, genistein, equol, apigenin, genistin, genistein, biochanin, coumestrol, formononetin, resveratrol, secoisolariciresinol diglucoside, and lignan. The phytoestrogens can promote the vaginal mucous membrane epithelial cells to synthesize glycogen and promote the growth of beneficial lactobacillus, and the bacteriostatic composition containing the phytoestrogens is particularly suitable for menopause, postmenopause or postpartum.
In some embodiments, the vaginal bacteriostatic composition is used for restoring and/or maintaining normal vaginal flora, and/or restoring and/or maintaining normal vaginal microecology, and/or restoring and/or maintaining normal acidity, and/or cleaning and caring vagina and/or vulva, and/or relieving and/or eliminating vaginal vulvar pruritus, and/or pain, and/or dryness, and/or irritation, and/or dyspareunia, and/or relieving and/or eliminating abnormal leucorrhea, and/or abnormal leucorrhea.
In some embodiments, the vaginal bacteriostatic composition for regulating vaginal flora according to the invention is used for preventing and/or treating vaginal flora imbalance, and/or bacterial vaginosis, and/or aerobic vaginitis, and/or cytolytic vaginosis, and/or vulvocandidiasis vaginosis, and/or atrophic vaginitis.
The present invention also provides the use of a fatty acid and/or a salt thereof in the manufacture of a bacteriostatic composition for modulating vaginal flora, said fatty acid being selected from at least one of the group consisting of butyric acid, valeric acid, caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, undecanoic acid, undecylenic acid, and lauric acid, said fatty acid and/or salt thereof being present in a total amount in the composition in the range of 0.001-2.00% (w/w), calculated as 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 fatty acids and/or salts thereof selected from the group consisting of butyric acid, caproic acid, caprylic acid, capric acid, undecanoic acid, or mixtures thereof.
In some embodiments, the use of a fatty acid and/or salt thereof according to the present invention in the manufacture of a bacteriostatic composition for modulating vaginal flora, wherein the fatty acid and/or salt thereof has the same concentration or properties as the fatty acid and/or salt thereof used in the methods of modulating vaginal flora of the present disclosure.
In some embodiments, the use of a fatty acid and/or salt thereof according to the present invention in the manufacture of a bacteriostatic composition for modulating vaginal flora, wherein modulating vaginal flora is of the same type as modulating vaginal flora in the methods of modulating vaginal flora of the present disclosure, i.e., comprising at least one of: inhibiting vaginal abnormal flora, restoring and/or maintaining vaginal lactobacilli.
In some embodiments, the fatty acid and/or salt thereof according to the invention is used for preparing a bacteriostatic composition for modulating vaginal flora, wherein the vaginal flora modulation comprises the vaginal bacteriostatic composition used for restoring and/or maintaining normal vaginal flora, and/or restoring and/or maintaining normal vaginal micro-ecology, and/or restoring and/or maintaining normal acidity of vagina, and/or cleaning and caring vagina and/or vulva, and/or reducing and/or eliminating vaginal vulvar pruritus, and/or pain, and/or dryness, and/or irritation, and/or dyspareunia, and/or reducing and/or eliminating abnormal leucorrhea, and/or abnormal leucorrhea taste.
In some embodiments, the use of a fatty acid and/or a salt thereof according to the invention for the preparation of a bacteriostatic composition for modulating vaginal flora, wherein said modulating vaginal flora comprises the use of a bacteriostatic vaginal composition for the prevention and/or treatment of disorders of vaginal flora, and/or bacterial vaginosis, and/or aerobic vaginitis, and/or cytolytic vaginosis, and/or vulvocandidiasis vaginosis, and/or atrophic vaginitis.
The invention also provides a preparation method of the antibacterial composition, which comprises the following steps: adding the following components into an excipient matrix, wherein the excipient matrix is an aqueous solution or a water-soluble colloid or a foaming agent or an excipient matrix of a suppository or a tablet:
(1) One or more fatty acids and/or salts thereof in a total content in the range of 0.001-3.00% (w/w) based on 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, 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;
(2) One or more dibasic acids and/or salts thereof selected from the group consisting of: glutaric, adipic, pimelic, preferably adipic acid;
(3) One or more aromatic alcohols selected from the group consisting of: benzyl alcohol, 2,4-dichlorobenzyl alcohol, phenethyl alcohol, phenoxyethanol, and cinnamyl alcohol, preferably phenethyl alcohol, cinnamyl alcohol, or mixtures thereof.
(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;
the composition adopts one of the following dosage forms: the medicament can be water solution, water-soluble gel, foam, spray, ointment, powder, membrane, capsule, suppository and tablet, preferably water solution, water-soluble gel, foam, spray or ointment.
In some embodiments, wherein the total content of the one or more fatty acids and/or salts thereof added in the preparation process, 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 said 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 said added aromatic alcohol(s) 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 said one or more aromatic acids and/or salts thereof added, based on the aromatic acid, 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 the preparation of the water-soluble colloid agent, a non-flowable, viscous and water-soluble colloid matrix is selected, and the matrix enables the composition to be in uniform contact with vaginal mucosa and stay for a long time so as to play a role. In some embodiments, the matrix is xanthan gum, and/or carbomer, and/or polycarbophil, and/or dextran, and/or glucomannan, and/or tragacanth, and/or Methylcellulose (MC), and/or carboxymethylcellulose (CMC), and/or Hydroxyethylcellulose (HEC), and/or Hydroxyethylmethylcellulose (HEMC), and/or Hydroxypropylmethylcellulose (HPMC), preferably xanthan gum, carbomer.
In some embodiments, the composition may be prepared according to the following process scheme: quantitatively measuring (1) one or more fatty acids and/or salts thereof such as propionic acid and/or sodium salts 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 phenethyl alcohol, (4) one or more aromatic acids and/or salts thereof such as benzoic acid and/or sodium salts thereof, (5) one or more colloid matrixes such as xanthan gum and other components, and the like according to the proportion, uniformly mixing, quantitatively adding distilled water, stirring, uniformly mixing, dissolving each component, and swelling the colloid matrix to form uniform colloid; the pH of the composition is adjusted with an acid and/or a base to a range of 3.1-4.8, preferably 3.6-4.6, more preferably 3.8-4.4. In some embodiments, a sterilization process may be further performed, and the sterilization process may be selected from the following processes: sterilizing by radiation, high temperature (such as 115.6 deg.C, 15-20 min; or 100 deg.C, 30 min), or intermittent (such as treating at 80 deg.C for 30 min, then at 36 deg.C for 5-10 hr, then at 80 deg.C for 30 min, then at 36 deg.C for 5-10 hr, and finally at 80 deg.C for 30 min). Alternatively, in some embodiments, the benzoic acid and/or its sodium salt, etc. are formulated separately as a solution, filter sterilized, and then added to a sterilized water-soluble gum base.
In some embodiments, when preparing a solution, the above components except xanthan gum can be mixed well, water is added to dissolve the components, and the solution is sterilized and packaged separately; or dissolving the above components, filtering, and packaging.
In some embodiments, when preparing a cream-type ointment, the choice of matrix and the specific preparation process may be made by methods known to those skilled in the art, for example, as described in pharmacy, eds Fang Liang (see reference 1 for details).
In some embodiments, when preparing tablets, the fatty acid and/or its salt, the dibasic acid and/or its salt, the aromatic alcohol, the aromatic acid and/or its salt, and other components are quantitatively mixed with the filling excipients uniformly and directly compressed to obtain tablets, which can be prepared by methods known to those skilled in the art, for example, the method described in "pharmacy" of Fang Liang, the main edition of 5363 (see reference 2 for details); optionally adding adjuvants such as lubricant such as magnesium stearate or disintegrant such as carboxymethyl starch sodium, mixing, and tabletting. In some embodiments, the prepared tablet may also be dispensed into a drug delivery device, or a sterile device, or a medical device, or a pharmaceutical device.
In some embodiments, when preparing films, suppositories, and the like, reference may be made to methods known to those of skill in the art, for example, as described in pharmacy, eds Fang Liang (see in particular references 3, 4).
In some embodiments, when preparing a sanitary napkin, a sanitary pad, or a tampon containing the bacteriostatic composition of the present disclosure, the components of the fatty acid and/or its salt, the dibasic acid and/or its salt, the aromatic alcohol, the aromatic acid and/or its salt, such as sodium benzoate, sodium propionate, caproic acid, phenethyl alcohol, adipic acid, and other components, etc., can be quantitatively weighed, added with the corresponding adjuvant components, made into powder, or film, or tablet, or capsule, and then placed inside the sanitary napkin, the sanitary pad, or the tampon, etc., by a suitable manner or process; or by attaching the components of the fatty acid and/or salt thereof, dibasic acid and/or salt thereof, aromatic alcohol, aromatic acid and/or salt thereof, such as sodium propionate, caproic acid, phenethyl alcohol, sodium benzoate, adipic acid, and other components, and the like, of the present disclosure, and suitable auxiliary components, to the inner layer material of the sanitary napkin, panty liner, tampon, or the like, by a suitable process.
In some embodiments, when prepared in dosage forms such as capsules, or suppositories, or tablets, each unit dosage form contains a specific range of content of each component of the composition of the present disclosure. For example, one or more fatty acids and/or salts thereof in a total amount of 0.00005 to 0.15 grams, one or more dibasic acids and/or salts thereof in a total amount of 0.0025 to 0.25 grams, one or more aromatic alcohols in a total amount of 0.0015 to 0.050 grams, one or more aromatic acids and/or salts thereof in a total amount of 0.0015 to 0.05 grams, based on the total amount of the aromatic acids, per unit dosage form; preferably, each unit dosage form contains a total amount of one or more fatty acids and/or salts thereof in the range of 0.00005 to 0.100 grams of a total amount of fatty acids, one or more dibasic acids and/or salts thereof in the range of 0.005 to 0.175 grams of a total amount of dibasic acids and/or salts thereof in the range of dibasic acids and/or polybasic acids, one or more aromatic alcohols in the total amount of 0.0015 to 0.035 grams of a total amount of aromatic acids, and one or more aromatic acids and/or salts thereof in the total amount of 0.0015 to 0.025 grams of a total amount of aromatic acids and/or salts thereof in the range of aromatic acids.
Various organic acids or salts thereof used in the preparation method of the present disclosure, such as fatty acids and/or salts thereof, or dibasic acids and/or salts thereof, or aromatic acids and/or salts thereof, and the like, are dissolved in water to form unionized molecules and ionized ions, and the ratio of unionized molecules to ionized ions depends on the pH of the solution and the ionization constant pKa of the organic acid. It can be seen that both the organic acid and the salt thereof are organic acid molecules or organic acid radical ions after being dissolved in water, and from this viewpoint, the two are not substantially different.
Reference will now be made in detail to various exemplary embodiments of the invention, the detailed description should not be construed as limiting the invention but as a more detailed description of certain aspects, features and embodiments of the invention. It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. Further, for numerical ranges in this disclosure, it is understood that the upper and lower limits of the range, and each intervening value therebetween, is specifically disclosed. Every smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in a stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range.
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 invention belongs. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference herein for the purpose of disclosing and describing the methods and/or materials associated with the documents. In case of conflict with any incorporated document, the present specification will control. Unless otherwise indicated, "%" is percent by weight.
The bacteriostatic agents commonly used for skin and/or mucous membrane cleaning, bacteriostasis or disinfection, such as povidone iodine, chlorhexidine and the like, are broad-spectrum bacteriostatic agents which not only inhibit escherichia coli, staphylococcus aureus, fungi and the like, but also inhibit lactic acid bacteria such as lactobacillus and the like. Commonly used antiseptics for skin care products, cosmetics, bath products and the like, and commonly used antiseptics for medical products and medicines, such as chlorobutanol, benzalkonium chloride and the like, also have inhibiting effect on lactobacillus and the like. There is no highly selective bacteriostatic agent or bacteriostatic composition having a strong inhibitory effect on harmful bacteria and a weak inhibitory effect on beneficial bacteria such as lactobacillus.
The prior art (for example, PCT/CN2017/105296, zl201080036139 and US 8765819) disclose compositions comprising low-concentration bacteriostatic agents, such as low-concentration phenethyl alcohol, propionic acid and/or salts thereof, and/or benzoic acid and/or salts thereof, and the like, wherein the compositions containing the low-concentration bacteriostatic agents can inhibit escherichia coli and staphylococcus aureus, and the bacteriostatic rate of the escherichia coli and staphylococcus aureus can reach more than 50% and the bacteriostatic rate of candida albicans is lower and is less than 50% according to a test method and a result judgment standard in the national standard of people's republic of health standard for disposable sanitary products (GB 15979-2002).
The concentration of the bacteriostatic agent is increased, and the bacteriostatic action on candida albicans can be enhanced. Research shows that the concentration of each component in the bacteriostatic agent combination of propionic acid and/or propionic salt, benzoic acid and/or benzoic alcohol and phenethyl alcohol is properly increased, so that the bacteriostatic action of the bacteriostatic agent combination can be enhanced, escherichia coli, staphylococcus aureus and the like can be more effectively inhibited, and the inhibition rate of candida albicans is more than 50%. However, the higher the concentration of the bacteriostatic agent is, the stronger the inhibitory effect on lactic acid bacteria such as lactobacillus is. As shown in experimental example one disclosed in PCT/CN2017/105296, when the concentration of sodium propionate is 0.40% (w/v), 0.50% (w/v), lactobacillus growth is not significantly inhibited; the growth of Lactobacillus was inhibited at a sodium propionate concentration of 0.70% (w/v). When the concentration of phenethyl alcohol was 0.40% (w/v), the growth of lactobacillus was not significantly inhibited; however, at a concentration of 0.50% (w/v) phenethyl alcohol, growth and acid production of Lactobacillus were inhibited.
The inventors have continued intensive studies in order to further develop a bacteriostatic composition which is effective in inhibiting harmful microorganisms but not inhibiting beneficial bacteria such as lactobacilli and which is useful for skin and/or mucous membrane cleaning, or bacteriostatic or disinfecting, and a bacteriostatic composition which is useful as a preservative for skin care products, cosmetics, bath products and the like, and as a preservative for medical products and medicines. It is found that the proper fatty acid and/or salt thereof is selectively combined with dibasic acid, aromatic alcohol, aromatic acid and the like, so that the synergistic bacteriostatic action is realized on staphylococcus aureus and escherichia coli, the synergistic bacteriostatic action is also realized on candida albicans and the like, and the growth of pseudomonas aeruginosa and aspergillus niger is also remarkably inhibited. The prepared antibacterial composition is applied to the vagina, can obviously reduce abnormal flora in the vagina and obviously increase lactobacillus, and has the effect of regulating vaginal flora and vaginal acidity. Thus, the bacteriostatic compositions of the present disclosure may be used for cleansing or bacteriostatic or disinfecting the skin and/or mucous membranes; and for the preservation of bath products, skin care products, cosmetics, and for the preservation of medical products, pharmaceuticals, and the like.
To facilitate an understanding of the precise meaning of a term or phrase, or expression, or standard set forth herein, the following meaning will be understood, unless otherwise indicated:
"Lactobacillus" refers to a bacterium of the genus Lactobacillus, lactobacillus in English, which is a gram-positive, rod-shaped, spore-free bacterium capable of fermenting metabolizable sugars to produce large amounts of lactic acid, and comprises hundreds of species and subspecies.
"lactic acid bacteria" is a general term for bacteria capable of metabolizing fermentable carbohydrates to produce a large amount of lactic acid, and includes bacteria of 18 genera and 200 species or more. Among them, lactobacillus is also a lactic acid bacterium.
"vaginal normal flora" means vaginal flora Nugent score of 1-3. The bacteria in the vagina are mainly lactobacillus, and the number of the bacteria is large, and the number of the bacteria in other kinds is small. The "other kinds of bacteria" include gram-positive cocci such as staphylococci, streptococci, etc., gram-negative bacilli such as Gardnerella vaginalis, escherichia coli, etc., gram-negative cocci such as Veillonella, etc., obligate anaerobic Prevotella, curvulus mobilis, etc.
"vaginal abnormal flora" means vaginal flora Nugent score of 5-10. The number of lactobacilli in the vagina is small and the number of other species is high. The "other kinds of bacteria" include gram-positive cocci such as staphylococci, streptococci, etc., gram-negative bacilli such as Gardnerella vaginalis, escherichia coli, etc., gram-negative cocci such as Veillonella, etc., obligate anaerobic Prevotella, curvulus mobilis, etc.
"harmful microorganism" broadly refers to various strongly pathogenic microorganisms, or various conditionally pathogenic microorganisms that are pathogenic when human immunity is reduced, or microorganisms that cause spoilage of foods, pharmaceuticals, cosmetics, sanitary products, etc., including but not limited to microorganisms of the following groups: candida, staphylococcus aureus, escherichia coli, pseudomonas aeruginosa, gardnerella vaginalis, prevotella, campylobacter mobilis, aspergillus niger, abnormal flora of the skin and/or mucosa, and viruses HPV, HIV, etc.
"component" refers to various ingredients in the composition, including bacteriostats, as well as other ingredients that are not bacteriostatic.
"bacteriostatic agent" refers to various ingredients or combinations thereof having bacteriostatic effects, and is not limited to conventional bacteriostatic agents or combinations thereof recognized by those skilled in the art.
The bacteriostat rate refers to the bacteriostat rate of the bacteriostat on Escherichia coli, staphylococcus aureus, candida albicans and the like according to the inspection method and judgment standard in appendix C of GB15979-2002 hygienic Standard for Disposable sanitary articles.
"bacteriostatic action" refers to the inhibitory action of a bacteriostatic agent on bacteria, fungi, etc. The strength of the bacteriostatic action is judged by the bacteriostatic rate, which is as follows: the bacteriostasis rate is more than 50 percent, which is 'has bacteriostasis function'; the bacteriostasis rate is more than 90 percent, which is 'strong bacteriostasis'.
The 'low-concentration bacteriostatic agent' refers to bacteriostatic agent with the bacteriostatic rate of less than 50% and lower concentration on candida albicans.
The high-concentration bacteriostatic agent refers to bacteriostatic agent with higher concentration and higher bacteriostatic rate of Candida albicans.
"no difference in bacteriostatic rate" or "no influence on bacteriostatic action", means that the difference between the two bacteriostatic rates is less than 15%.
"differential bacteriostasis rate" or "influence on bacteriostasis" means that the difference between the two bacteriostasis rates is 15-30%.
"significant difference in bacteriostatic rate" or "significant influence on bacteriostatic action" means that the difference between the two bacteriostatic rates is greater than 30%.
The synergistic bacteriostasis refers to that the bacteriostasis rate of the combination of two or more than two bacteriostats to Escherichia coli, staphylococcus aureus or Candida albicans is higher than the sum of the bacteriostasis rates of the bacteriostats acting alone by more than 15 percent.
Example 1
This example is a variety of exemplary compositions of bacteriostatic compositions. Hereinafter, unless otherwise specifically stated, exemplary components in the composition refer to the following:
propionic acid CAS:79-09-4, adipic acid CAS:124-04-9, phenethyl alcohol (2-phenylethanol) CAS:60-12-8, butyric acid (n-butyric acid) CAS:107-92-6, caproic acid (n-hexanoic acid) CAS:142-62-1, pimelic acid CAS:111-16-0, malic acid (L-malic 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, caprylic acid (n-caprylic acid) CAS:124-07-2, nonanoic acid (n-nonanoic acid) CAS:112-05-0, capric acid (n-capric acid) CAS:334-48-5, undecanoic acid (undecanoic acid) CAS:112-37-8, cinnamyl alcohol (3-phenyl-2-propen-1-ol) CAS:104-54-1, succinic acid (succinic acid) CAS:110-15-6, tartaric acid (L-tartaric acid) CAS:87-69-4, maleic acid (maleic acid) CAS:110-16-7, CAS citrate: 77-92-9, fumaric acid (fumaric acid) CAS:110-17-8, undecylenic acid (10-undecylenic acid) CAS:112-38-9, glutaric acid CAS:110-94-1.
Example 1:
adding 1.50 g of adipic acid, 2.00 g of propionic acid, 0.25 g of phenethyl alcohol, 1.00 g of citric acid and 2.50 g of maltose into 80 g of purified water, stirring to dissolve the adipic acid, the propionic acid, the phenethyl alcohol, the citric acid and the maltose, adding 2.15 g of xanthan gum, supplementing the purified water to 100 g of total weight, stirring and swelling to form uniform viscous jelly, adjusting the pH to 3.1 by using 1.0mol/L of sodium hydroxide solution, adjusting the temperature to 115.6 ℃, and sterilizing for 15 minutes to obtain the water-soluble colloid composition.
Example 2:
the following raw materials were weighed out in the following proportions and prepared essentially as in example 1 to give 100 g of the composition:
example 3:
the following raw materials were weighed out in the following proportions and prepared essentially as in example 1 to give 100 g of the composition:
example 4:
the following raw materials were weighed out in the following proportions and 100 g of the composition was prepared essentially as in example 1:
example 5:
the following raw materials were weighed out in the following proportions and 100 g of the composition was prepared essentially as in example 1:
example 6:
the following raw materials were weighed out in the following proportions and 100 g of the composition was prepared essentially as in example 1:
example 7:
the following raw materials were weighed out in the following proportions and prepared essentially as in example 1 to give 100 g of the composition:
example 8:
the following raw materials were weighed out in the following proportions and prepared essentially as in example 1 to give 100 g of the composition:
example 9:
the following raw materials were weighed out in the following proportions and 100 g of the composition was prepared essentially as in example 1:
example 10:
the following raw materials were weighed out in the following proportions and 100 g of the composition was prepared essentially as in example 1:
example 11:
the following raw materials were weighed out in the following proportions and 100 g of the composition was prepared essentially as in example 1:
example 12:
the following raw materials were weighed out in the following proportions and 100 g of the composition was prepared essentially as in example 1:
example 13:
the following raw materials were weighed out in the following proportions and 100 g of the composition was prepared essentially as in example 1:
example 14:
the raw materials were weighed out in the proportions described below and 100 g of the composition was prepared essentially as in example 1.
1.50 g of adipic acid, 0.20 g of benzoic acid and 1.25 g of propionic acid;
0.76 g of glutamic acid, 0.34 g of glutamine, 0.60 g of aspartic acid, 0.98 g of asparagine, 0.31 g of isoleucine, 0.35 g of methionine, 0.20 g of phenylalanine, 0.46 g of valine, 0.78 g of leucine and 0.89 g of proline;
xanthan gum 2.50 g, adding purified water to total weight of 100 g, adjusting pH to 4.0
Example 15:
the ingredients were weighed out in the proportions described below and 100 g of the composition was prepared essentially as in example 1.
Example 16
Tablets each containing 60 mg of adipic acid, 5 mg of sodium benzoate, 30 mg of propionic acid, 60 mg of sucrose were prepared substantially in accordance with the method of reference 1.
Example 17
Pessaries containing 60 mg of adipic acid, 5 mg of sodium benzoate, 30 mg of propionic acid, and 60 mg of maltose were prepared per granule substantially in accordance with the method of reference 3.
Example 2
This example serves to verify the effect of the composition.
In vitro experiment 1
Basically according to the method of GB15979-2002 appendix C of sanitary Standard for Disposable sanitary articles, the bacteriostasis rate of the solution of different component combinations on Candida albicans ATCC10231 is studied for 20 minutes, wherein the percentage concentrations of the components are weight percentage concentration% (w/w), the pH values are 3.8, and the experimental results are shown in Table 1:
TABLE 1 bacteriostatic effect of different combinations of solutions on Candida albicans ATCC10231
Numbering | Propionic acid (%) | Adipic acid (%) | Benzyl alcohol (%) | Sodium benzoate (%) | Bacteriostatic ratio (%) |
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 |
The results show that:
1. as can be seen from the experimental results of group 1 in Table 1, when the pH value is 3.8, the combined solution of the three components, namely '0.50% propionic acid, 1.50% adipic acid and 0.20% sodium benzoate', has an antibacterial effect on Candida albicans, and the antibacterial rate is 61.29%;
2. as shown in the experimental results of the groups 2-3 in Table 1, when the pH value is 3.8, the combined solution of the three components, namely '0.50% propionic acid, 1.50% adipic acid and 0.20% sodium benzoate', and 2 kinds of benzyl alcohol with different concentrations (0.50% and 0.70%) has a strong bacteriostatic action or bacteriostatic action on Candida albicans, and the bacteriostatic rates are 81.52% and 99.27%, respectively.
In summary, comparing the experimental results of groups 2-3 with those of group 1 shows that: when the pH value is 3.8, 0.50% and 0.70% of benzyl alcohol have obvious influence on the effect of a solution formed by combining three components of 0.50% of propionic acid, 1.50% of adipic acid and 0.20% of sodium benzoate on inhibiting candida albicans, and can enhance the bacteriostatic action.
In vitro experiment 2
Basically according to the method of GB15979-2002 appendix C of sanitary Standard for Disposable sanitary articles, the bacteriostasis rate of the solution of different component combinations on Candida albicans ATCC10231 is studied for 20 minutes, wherein the percentage concentrations of the components are weight percentage concentration% (w/w), the pH values are 4.0, and the experimental results are shown in Table 2:
TABLE 2 bacteriostatic effect of different combinations of solutions on Candida albicans ATCC10231
Numbering | Propionic acid (%) | Adipic acid (%) | Phenethyl alcohol (%) | 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 |
The results show that:
1. as can be seen from the experimental results of group 1 of table 2: when the pH value is 4.0, the bacteriostatic rate of 1.50% propionic acid, 0.35% phenethyl alcohol and 0.20% benzoic acid on candida albicans is 15.91%;
2. as can be seen from the experimental results of group 2 of table 2: when the pH value is 4.0, the bacteriostasis rate of 1.50 percent of propionic acid, 0.35 percent of phenethyl alcohol and 0.25 percent of benzoic acid to the candida albicans is 46.09 percent;
3. as can be seen from the experimental results of group 3 of table 2: when the pH value is 4.0, the solution of 1.50% propionic acid, 1.50% adipic acid, 0.35% phenethyl alcohol and 0.20% benzoic acid has an antibacterial effect on candida albicans, and the antibacterial rate is 67.39%;
4. as can be seen from the 4 th set of experimental results of table 2: when the pH value is 4.0, the solution of 1.50% propionic acid, 1.50% adipic acid, 0.35% phenethyl alcohol and 0.25% benzoic acid has strong bacteriostatic action on candida albicans, and the bacteriostatic rate is 92.17%.
In summary, the following steps:
1. comparing the experimental results of the groups 1 and 2, and the groups 3 and 4, it can be seen that: when the pH value is 4.0, the concentration of the benzoic acid is increased from 0.20% to 0.25%, the effect of a solution containing 1.50% of propionic acid and 0.35% of phenethyl alcohol and a solution containing the combination of 1.50% of propionic acid, 1.50% of adipic acid and 0.35% of phenethyl alcohol on inhibiting the candida albicans is influenced or remarkably influenced, and the bacteriostatic effect is enhanced;
2. comparing the experimental results of the groups 1 and 3, and the groups 2 and 4, it can be seen that: when the pH value is 4.0, 1.50% of adipic acid has obvious influence on the effect of a solution formed by combining 1.50% of propionic acid, 0.35% of phenethyl alcohol and 0.20% of benzoic acid and a solution formed by combining 1.50% of propionic acid, 0.35% of phenethyl alcohol and 0.25% of benzoic acid on inhibiting candida albicans, and the antibacterial effect is enhanced.
In vitro experiment III
Basically according to the method of GB15979-2002 appendix C of sanitary Standard for Disposable sanitary articles, the bacteriostasis rate of the solution of different component combinations on Candida albicans ATCC10231 is studied for 20 minutes, wherein the percentage concentrations of the components are weight percentage concentration% (w/w), the pH values are 3.8, and the experimental results are shown in Table 3:
TABLE 3 bacteriostatic effect of different combinations of solutions on Candida albicans ATCC10231
Number of | Propionic acid (%) | Adipic acid (%) | Benzyl alcohol (%) | Sodium benzoate (%) | Bacteriostatic ratio (%) |
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 |
The results show that:
1. as can be seen from the experimental results of group 1 of table 3: when the pH value is 3.8, the bacteriostasis rate of a solution formed by combining 1.35% of adipic acid, 0.25% of benzyl alcohol and 0.20% of sodium benzoate on the candida albicans is 45.12%;
2. as can be seen from the results of the experiments in groups 2-5 of Table 3: at a pH value of 3.8, solutions of 4 propionic acids (0.50%, 1.25%, 1.50% and 3.00%) with different concentrations, which are respectively combined with 1.35% adipic acid, 0.25% benzyl alcohol and 0.20% sodium benzoate, have strong bacteriostatic action or bacteriostatic action on candida albicans, and the bacteriostatic rates are respectively 61.60%, 89.72%, 94.42% and 100.00%.
In conclusion, compared with groups 2-5 and 1, when the pH value is 3.8, propionic acid has an influence or significant influence on the candida albicans inhibition effect of a solution containing the combination of 1.35% of adipic acid, 0.25% of benzyl alcohol and 0.20% of sodium benzoate, the bacteriostatic action is enhanced, and the higher the propionic acid concentration is, the stronger the bacteriostatic action on candida albicans is.
In vitro experiment four
Basically according to the method of GB15979-2002 appendix C of sanitary Standard for Disposable sanitary articles, the bacteriostasis rate of the solution of different component combinations on Candida albicans ATCC10231 is studied for 20 minutes, wherein the percentage concentrations of the components are weight percentage concentration% (w/w), the pH values are 4.3, and the experimental results are shown in Table 4:
TABLE 4 bacteriostatic effect of different combinations of solutions on Candida albicans ATCC10231
Numbering | Propionic acid (%) | Adipic acid (%) | Phenethyl alcohol (%) | 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 |
The results show that:
1. as can be seen from the experimental results of group 1 of table 4: when the pH value is 4.3, the bacteriostasis rate of the solution of 0.54 percent of propionic acid, 1.50 percent of adipic acid and 0.30 percent of phenethyl alcohol to the candida albicans is 26.05 percent;
2. as can be seen from the experimental results of groups 2 and 3 of table 4: at a pH value of 4.3, solutions of 0.54% propionic acid, 1.50% adipic acid and 0.30% phenethyl alcohol respectively combined with 0.50% benzoic acid and 1.00% benzoic acid have strong bacteriostatic action or bacteriostatic action on candida albicans, and the bacteriostatic rates are 64.80% and 100.00% respectively.
In conclusion, at a pH of 4.3, 0.50% and 1.00% benzoic acid significantly affect the inhibition effect of the solution containing the combination of "0.54% propionic acid, 1.50% adipic acid, and 0.30% phenethyl alcohol" on candida albicans, and the bacteriostatic effect is enhanced, and the higher the benzoic acid concentration is, the stronger the bacteriostatic effect on candida albicans is.
In vitro experiment five
Basically according to the method of annex C of GB15979-2002 hygienic Standard for Disposable sanitary products, the bacteriostasis rate of the solution with different component combinations on the Candida albicans ATCC10231 is researched for 20 minutes, wherein the percentage concentration of each component is weight percentage concentration (w/w), the pH value is 4.6, and the experimental result is shown in Table 5:
TABLE 5 bacteriostatic action of different solution combinations on Candida albicans ATCC10231
Numbering | Propionic acid (%) | Adipic acid (%) | Phenethyl alcohol (%) | Sodium benzoate (%) | Bacteriostatic ratio (%) |
1 | -- | 1.50 | 0.30 | 1.18 | 84.12 |
2 | 2.00 | 1.50 | 0.30 | 1.18 | 100.00 |
The results show that:
1. as can be seen from the experimental results of group 1 of table 5: when the pH value is 4.6, the combined solution of 1.50% of adipic acid, 0.30% of phenethyl alcohol and 1.18% of sodium benzoate has an antibacterial effect on candida albicans, and the antibacterial rate is 84.12%;
2. as can be seen from the experimental results of group 2 of table 5: when the pH value is 4.6, the solution of 2.00% propionic acid, 1.50% adipic acid, 0.30% phenethyl alcohol and 1.18% sodium benzoate has strong bacteriostatic action on the candida albicans, and the bacteriostatic rate is 100.00%.
In summary, comparing the experimental results of the group 1 and the group 2 shows that: at a pH of 4.6, 2.00% propionic acid had an effect on the Candida albicans inhibition by a solution containing 1.50% adipic acid, 0.30% phenethyl alcohol, and 1.18% sodium benzoate, and the bacteriostatic effect was enhanced.
In vitro experiment six
According to the method of appendix C of GB15979-2002 hygienic Standard for Disposable sanitary articles, the bacteriostasis rate of the solution of different component combinations on the Candida albicans ATCC10231 is studied for 20 minutes, wherein the percentage concentration of each component is weight percentage concentration (w/w), and the pH value is 3.8. The results of the experiment are shown in table 6:
TABLE 6 bacteriostatic effect of different solutions on Candida albicans ATCC10231
Number of | Butyric acid (%) | Hexanoic acid (%) | Adipic acid (%) | Phenethyl alcohol (%) | Phenoxyethanol (%) | Sodium benzoate (%) | Bacteriostatic ratio (%) |
1 | 0.88 | -- | -- | 0.40 | -- | 0.20 | 71.52 |
2 | -- | 0.12 | -- | 0.40 | -- | 0.20 | 70.65 |
3 | 0.88 | -- | -- | -- | 0.40 | 0.20 | 56.75 |
4 | -- | 0.12 | -- | -- | 0.40 | 0.20 | 35.88 |
5 | 0.88 | -- | 1.46 | 0.40 | -- | 0.20 | 100.00 |
6 | -- | 0.12 | 1.46 | 0.40 | -- | 0.20 | 100.00 |
7 | 0.88 | -- | 1.46 | -- | 0.40 | 0.20 | 100.00 |
8 | -- | 0.12 | 1.46 | -- | 0.40 | 0.20 | 100.00 |
The results show that:
1. as can be seen from the results of the experiments in groups 1-2 of Table 6: when the pH value is 3.8, the solutions of 0.20% sodium benzoate and 0.40% phenethyl alcohol which are respectively combined with 2 kinds of fatty acid (0.88% butyric acid and 0.12% caproic acid) with different concentrations have the bacteriostatic action on candida albicans, and the bacteriostatic rates are 71.52% and 70.65% respectively;
2. as can be seen from the results of the experiments in groups 3-4 of Table 6: when the pH value is 3.8, the combined solution of 0.20% sodium benzoate, 0.40% phenoxyethanol and 0.88% butyric acid has an antibacterial effect on candida albicans, and the antibacterial rate is 56.75%; the bacteriostasis rate of the solution of the combination of 0.20 percent of sodium benzoate, 0.40 percent of phenoxyethanol and 0.12 percent of caproic acid on the candida albicans is 35.88 percent;
3. as can be seen from the results of the 5 th to 6 th sets of experiments in Table 6: when the pH value is 3.8, solutions of 1.46% adipic acid, 0.20% sodium benzoate and 0.40% phenethyl alcohol which are respectively combined with 2 kinds of fatty acids (0.88% butyric acid and 0.12% caproic acid) with different concentrations have strong bacteriostatic action on the candida albicans, and the bacteriostatic rate is 100%;
4. as can be seen from the results of the 7 th to 8 th sets of experiments in Table 6: when the pH value is 3.8, solutions of 1.46% adipic acid, 0.20% sodium benzoate and 0.40% phenoxyethanol which are respectively combined with 2 fatty acids (0.88% butyric acid and 0.12% caproic acid) with different concentrations have strong bacteriostatic action on candida albicans, and the bacteriostatic rate is 100%.
In view of the above, it is desirable to provide,
1. comparing the results of the experiments in groups 5-6 and 1-2 of Table 6, it can be seen that: when the pH value is 3.8, 1.46% of adipic acid respectively has obvious influence on the effect of a solution formed by combining 0.20% of sodium benzoate, 0.40% of phenethyl alcohol, 0.88% of butyric acid, 0.20% of sodium benzoate, 0.40% of phenethyl alcohol and 0.12% of caproic acid on inhibiting candida albicans, and the bacteriostatic action is enhanced;
2. from the results of the experiments in groups 7-8 and 3-4 of Table 6, it can be seen that: when the pH value is 3.8, 1.46% of adipic acid respectively has obvious influence on the effect of a solution formed by combining 0.20% of sodium benzoate, 0.40% of phenoxyethanol, 0.88% of butyric acid, 0.20% of sodium benzoate, 0.40% of phenoxyethanol and 0.12% of caproic acid on the inhibition of candida albicans, and the antibacterial effect is enhanced.
Seven in vitro experiments
According to the method of appendix C of GB15979-2002 hygienic Standard for Disposable sanitary articles, the bacteriostasis rate of the solution of different component combinations on the Candida albicans ATCC10231 is studied for 20 minutes, wherein the percentage concentration of each component is weight percentage concentration (w/w), and the pH value is 3.8. The results of the experiment are shown in table 7:
TABLE 7 bacteriostatic action of different solutions on Candida albicans ATCC10231
Numbering | Propionic acid (%) | Pimelic acid (%) | Malic acid (%) | Phenethyl alcohol (%) | P-hydroxybenzoic 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 |
The results show that:
1. as can be seen from the experimental results of group 1 of table 7: when the pH value is 3.8, the solution formed by combining three components, namely 0.21 percent of p-hydroxybenzoic acid, 0.06 percent of phenethyl alcohol and 2.50 percent of propionic acid, has an antibacterial effect on candida albicans, and the antibacterial rate is 62.76 percent;
2. as can be seen from the experimental results of group 2 of table 7: when the pH value is 3.8, the solution of 1.60 percent pimelic acid, 0.21 percent p-hydroxybenzoic acid, 0.06 percent phenethyl alcohol and 2.50 percent propionic acid has strong bacteriostatic action on the candida albicans, and the bacteriostatic rate is 94.84 percent;
3. as can be seen from the experimental results of group 3 of table 7: when the pH value is 3.8, the solution of 1.34 percent malic acid combined with 0.21 percent p-hydroxybenzoic acid, 0.06 percent phenethyl alcohol and 2.50 percent propionic acid has the bacteriostasis function on candida albicans, and the bacteriostasis rate is 65.68 percent.
In summary, the following steps: comparing the experimental results of groups 2, 3 and 1, it can be seen that: when the pH value is 3.8, 1.60 percent pimelic acid has obvious influence on the effect of a combined solution containing 0.21 percent of p-hydroxybenzoic acid, 0.06 percent of phenethyl alcohol and 2.50 percent of propionic acid on inhibiting the candida albicans, and the bacteriostatic action is enhanced; while 1.34% malic acid has no effect on the effect of the combination of 0.21% p-hydroxybenzoic acid, 0.06% phenethyl alcohol and 2.50% propionic acid on the inhibition of candida albicans.
Eight in vitro experiments
According to the method of appendix C of GB15979-2002 hygienic Standard for Disposable sanitary articles, the antibacterial effect of the aqueous solution containing different components on Candida albicans ATCC10231 is researched, wherein the percentage concentration of each component is weight percentage concentration (w/w), and the pH value is 3.9. The results of the experiment are shown in table 8:
TABLE 8 bacteriostatic action of different solutions on Candida albicans ATCC10231
Numbering | Adipic acid (%) | Butyric acid (%) | Sodium benzoate (%) | Phenethyl alcohol (%) | Bacteriostatic ratio (%) |
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 |
The results show that:
1. as can be seen from the results of the experiments in sets 1-4 of Table 8: when the pH value is 3.9, 1.46 percent of adipic acid, 0.60 percent of butyric acid, 0.14 percent of sodium benzoate and 0.40 percent of phenethyl alcohol respectively and independently act, and the bacteriostasis rates to candida albicans are respectively 11.52 percent, 1.57 percent, 19.90 percent and-1.05 percent;
2. as can be seen from table 8, set 5 of experimental results: when the pH value is 3.9, the bacteriostasis rate of the solution of the combination of 1.46 percent of adipic acid and 0.60 percent of butyric acid on the candida albicans is 13.61 percent;
3. as can be seen from table 8, set 6 experimental results: when the pH value is 3.9, the bacteriostasis rate of the solution of the combination of 0.60 percent of butyric acid and 0.14 percent of sodium benzoate on the candida albicans is 17.80 percent;
4. as can be seen from table 8, set 7 of experimental results: when the pH value is 3.9, the bacteriostasis rate of the solution of the combination of 0.60 percent of butyric acid and 0.40 percent of phenethyl alcohol to the candida albicans is 8.90 percent;
5. as can be seen from table 8, set 8 of experimental results: when the pH value is 3.9, the bacteriostasis rate of the combined solution of 1.46 percent of adipic acid, 0.60 percent of butyric acid and 0.14 percent of sodium benzoate on the candida albicans is 27.23 percent;
6. as can be seen from table 8, set 9 of experimental results: when the pH value is 3.9, the bacteriostasis rate of the solution of the combination of 1.46 percent of adipic acid, 0.60 percent of butyric acid and 0.40 percent of phenethyl alcohol to the candida albicans is 25.65 percent;
7. as can be seen from table 8, set 10 of experimental results: when the pH value is 3.9, the bacteriostasis rate of the solution of the combination of 0.60 percent of butyric acid, 0.40 percent of phenethyl alcohol and 0.14 percent of sodium benzoate on the candida albicans is 2.62 percent;
8. as can be seen from table 8, set 11 of experimental results: when the pH value is 3.9, the bacteriostasis rate of the solution of the combination of 1.46 percent of adipic acid, 0.14 percent of sodium benzoate and 0.40 percent of phenethyl alcohol to the candida albicans is 42.41 percent;
9. as can be seen from table 8, set 12 of experimental results: when the pH value is 3.9, the combined solution of 1.46 percent of adipic acid, 0.60 percent of butyric acid, 0.14 percent of sodium benzoate and 0.40 percent of phenethyl alcohol has the bacteriostatic action on the candida albicans, and the bacteriostatic rate is 89.53 percent.
In summary, it can be seen that: when the pH value is 3.9, the bacteriostatic rate of the combination of 1.46% of adipic acid, 0.60% of butyric acid, 0.14% of sodium benzoate and 0.40% of phenethyl alcohol on the candida albicans is far higher than that of the combination of the single action, the combination of two or three components, and the synergistic bacteriostatic action of the combination of the four components on the candida albicans is suggested.
Nine in vitro experiments
According to the method of annex C of GB15979-2002 hygienic Standard for Disposable sanitary articles, the antibacterial effect of the aqueous solution of different component combinations on Candida albicans ATCC10231 is researched for 20 minutes, wherein the percentage concentration of each component is weight percentage concentration% (w/w), and the pH value of the solution is 4.3. The results of the experiment are shown in table 9:
TABLE 9 bacteriostatic action of different solutions on Candida albicans ATCC10231
Numbering | Hexanoic acid (%) | Adipic acid (%) | Sodium benzoate (%) | Phenethyl alcohol (%) | Bacteriostatic ratio (%) |
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 |
The results show that:
1. as can be seen from the results of the experiments in sets 1-4 of Table 9: when the pH value is 4.3, 1.35% of adipic acid, 0.20% of sodium benzoate, 0.18% of caproic acid and 0.30% of phenethyl alcohol respectively act independently, and the bacteriostasis rate to candida albicans is less than 10%;
2. as can be seen from table 9, set 5 of experimental results: when the pH value is 4.3, the solution formed by combining four components of 1.35 percent of adipic acid, 0.20 percent of sodium benzoate, 0.18 percent of caproic acid and 0.30 percent of phenethyl alcohol has an antibacterial effect on the candida albicans, and the antibacterial rate is 58.86 percent;
3. from the results of the 6 th to 9 th groups of experiments in Table 9, it can be seen that: when the pH value is 4.3, the bacteriostatic rate of the candida albicans strain is lower than 50% by using four components of 1.35% adipic acid, 0.20% sodium benzoate, 0.18% caproic acid and 0.30% phenethyl alcohol, and any solution lacking one component combination.
In summary, it can be seen that: the bacteriostasis rate of the solution formed by combining 1.35% of adipic acid, 0.20% of sodium benzoate, 0.18% of caproic acid and 0.30% of phenethyl alcohol on the candida albicans is obviously higher than that of the solution formed by combining any three of the adipic acid, the sodium benzoate, the caproic acid and the phenethyl alcohol and is also obviously higher than the sum of the bacteriostasis rates of the four components which respectively act independently, and the four components are prompted to have a synergistic bacteriostasis effect on the candida albicans.
Ten experiments in vitro
According to the method of appendix C of GB15979-2002 hygienic Standard for Disposable sanitary articles, the antibacterial effect of the aqueous solution of different component combinations on Candida albicans ATCC10231 is studied for 20 minutes, wherein the percentage concentration of each component is weight percentage concentration% (w/w), and the pH value of the solution is 3.8. The results of the experiment are shown in table 10:
TABLE 10 bacteriostatic action of different solutions of Candida albicans ATCC10231
Number of | Propionic acid (%) | Adipic acid (%) | Cinnamic acid (%) | Phenethyl alcohol (%) | Salicylic acid (%) | Bacteriostatic rate (%) |
1 | 1.50 | 1.50 | -- | 0.45 | -- | 30.96 |
2 | 1.50 | 1.50 | 0.03 | 0.45 | -- | 59.04 |
3 | 1.50 | 1.50 | 0.05 | 0.45 | -- | 71.19 |
4 | 1.50 | 1.50 | 0.08 | 0.45 | -- | 96.38 |
5 | 1.50 | 1.50 | 0.10 | 0.45 | -- | 100.00 |
6 | 1.50 | 1.50 | -- | 0.45 | 0.03 | 37.40 |
7 | 1.50 | 1.50 | -- | 0.45 | 0.05 | 55.58 |
8 | 1.50 | 1.50 | -- | 0.45 | 0.08 | 86.96 |
9 | 1.50 | 1.50 | -- | 0.45 | 0.10 | 94.81 |
The results show that:
1. as can be seen from table 10, set 1 experimental results: when the pH value is 3.8, the bacteriostasis rate of the solution with 1.50 percent of adipic acid, 0.45 percent of phenethyl alcohol and 1.50 percent of propionic acid on candida albicans is 30.96 percent;
2. as can be seen from the results of the experiments in Table 10, groups 2-5: when the pH value is 3.8, the solution of the combination of four cinnamic acids with different concentrations (0.03%, 0.05%, 0.08% and 0.10%) and 1.50% adipic acid, 0.45% phenethyl alcohol and 1.50% propionic acid has strong bacteriostatic action or bacteriostatic action on candida albicans, and the bacteriostatic rates are 59.04%, 71.19%, 96.38% and 100.00% respectively;
3. as can be seen from the results of the 6 th to 9 th sets of experiments in Table 10: at a pH value of 3.8, a solution of 0.03% salicylic acid combined with 1.50% adipic acid, 0.45% phenethyl alcohol and 1.50% propionic acid has an antibacterial rate of 37.40% on Candida albicans, and three solutions of salicylic acid with higher concentration (0.05%, 0.08% and 0.10%) combined with 1.50% adipic acid, 0.45% phenethyl alcohol and 1.50% propionic acid respectively have a strong antibacterial effect or bacteriostatic effect on Candida albicans, and the antibacterial rates are 55.58%, 86.96% and 94.81% respectively.
In summary, it can be seen that: 0.03-0.10% of cinnamic acid and 0.05-0.10% of salicylic acid have influence or obvious influence on the effect of a solution containing the combination of three components of 1.50% of adipic acid, 0.45% of phenethyl alcohol and 1.50% of propionic acid on inhibiting candida albicans, and the bacteriostasis is enhanced along with the increase of the concentration of the cinnamic acid or the salicylic acid.
Eleven in vitro experiments
According to the method of appendix C of GB15979-2002 hygienic Standard for Disposable sanitary articles, the antibacterial effect of the aqueous solution of different component combinations on Candida albicans ATCC10231 is studied for 20 minutes, wherein the percentage concentration of each component is weight percentage concentration% (w/w), and the pH value of the solution is 3.8. The results of the experiment are shown in table 11:
TABLE 11 bacteriostatic effect of different solutions on Candida albicans ATCC10231
The results show that:
1. as can be seen from the results of the experiments in Table 11, groups 1-6: when the pH value is 3.8, 0.001-0.002% of undecanoic acid, 0.001-0.002% of undecylenic acid and 0.001-0.002% of lauric acid have independent effects, and the bacteriostasis rate to candida albicans is lower than 15%;
2. as can be seen from table 11, set 7 experimental results: when the pH value is 3.8, the solution formed by combining three components, namely 0.20% sodium benzoate, 0.25% phenethyl alcohol and 1.50% adipic acid, has an antibacterial effect on candida albicans, and the antibacterial rate is 50.02%;
3. as can be seen from the results of the experiments in sets 8-9 of Table 11: when the pH value is 3.8, the solution formed by respectively combining three components of 0.20% sodium benzoate, 0.25% phenethyl alcohol and 1.50% adipic acid with two types of undecanoic acid (0.001% and 0.002%) with different concentrations has strong bacteriostatic action on candida albicans, and the bacteriostatic rate is higher than 90%;
4. as can be seen from the results of the experiments in Table 11, groups 10-11: when the pH value is 3.8, the solution formed by respectively combining three components of 0.20% sodium benzoate, 0.25% phenethyl alcohol and 1.50% adipic acid with two types of undecylenic acid (0.001% and 0.002%) with different concentrations has an antibacterial effect on candida albicans, and the antibacterial rate is higher than 50%;
5. from the results of the experiments in groups 12-13 of Table 11, it can be seen that: when the pH value is 3.8, the solution formed by combining three components, namely 0.20% sodium benzoate, 0.25% phenethyl alcohol and 1.50% adipic acid, with two lauric acids (0.001% and 0.002%) with different concentrations respectively has strong bacteriostatic action on candida albicans, and the bacteriostatic rate is 100%.
In summary, it can be seen that: 0.001-0.002% of undecanoic acid, 0.002% of undecylenic acid and 0.001-0.002% of lauric acid respectively have obvious influence on the effect of a solution containing the combination of 0.20% of sodium benzoate, 0.25% of phenethyl alcohol and 1.50% of adipic acid on inhibiting candida albicans, and the bacteriostatic action is enhanced.
Twelve in vitro experiments
According to the method of annex C of GB15979-2002 hygienic Standard for Disposable sanitary articles, the antibacterial effect of the aqueous solution of different component combinations on Candida albicans ATCC10231 is researched for 20 minutes, wherein the percentage concentration of each component is weight percentage concentration% (w/w). The results of the experiments are shown in tables 12-14:
TABLE 12 bacteriostatic effect of different solutions alone on Candida albicans ATCC10231
TABLE 13 bacteriostatic action of solutions of different components combined two by two on Candida albicans ATCC10231
TABLE 14 bacteriostatic action of the solutions of the three different combinations of components on Candida albicans ATCC10231
The results show that:
1. as can be seen from the experimental results of table 12: when the pH value is 3.6-3.8, 10 fatty acids (2.00% propionic acid, 2.20% butyric acid, 0.60% valeric acid, 0.20% caproic acid, 0.07% heptanoic acid, 0.02% caprylic acid, 0.009% pelargonic acid, 0.002% capric acid, 0.001% undecanoic acid and 0.001% lauric acid) and 0.25% sodium benzoate with different concentrations respectively act independently, and the bacteriostasis rate of the candida albicans is less than 20%;
2. as can be seen from the experimental results of table 13: when the pH value is 3.6-3.8, 0.20-0.25% of sodium benzoate and solutions respectively combined with 10 fatty acids (2.00% of propionic acid, 2.20% of butyric acid, 0.60% of valeric acid, 0.20% of caproic acid, 0.07% of heptanoic acid, 0.02% of caprylic acid, 0.009% of pelargonic acid, 0.002% of capric acid, 0.001% of undecanoic acid and 0.001% of lauric acid) with different concentrations have an antibacterial effect on candida albicans, and the antibacterial rate is more than 50%, so that the two components have synergistic antibacterial effect on candida albicans and enhanced antibacterial effect;
3. as can be seen from the experimental results of table 14: when the pH value is 3.6-3.8, the combined solution of 0.20% sodium benzoate and 0.40% phenethyl alcohol and 10 fatty acids (2.00% propionic acid, 2.20% butyric acid, 0.60% valeric acid, 0.20% caproic acid, 0.07% heptanoic acid, 0.02% caprylic acid, 0.009% pelargonic acid, 0.002% capric acid, 0.001% undecanoic acid and 0.001% lauric acid) with different concentrations has strong bacteriostatic action or bacteriostatic action on the candida albicans, and the bacteriostatic rate is between 50% and 90% or more than 90%, which indicates that the three component combination has synergistic bacteriostatic action on the candida albicans and enhanced bacteriostatic action.
Thirteen in vitro experiments
According to the method of appendix C of GB15979-2002 hygienic Standard for Disposable sanitary articles, the antibacterial effect of the aqueous solution of different component combinations on Candida albicans ATCC10231 is studied for 20 minutes, wherein the percentage concentration of each component is weight percentage concentration% (w/w), and the pH value is 3.8. The results of the experiment are shown in table 15:
TABLE 15 bacteriostatic action of different solutions on Candida albicans ATCC10231
The results show that:
1. as can be seen from the results of the experiments in sets 1-10 of Table 15: when the pH value is 3.8, 9 fatty acids (2.00% propionic acid, 2.20% butyric acid, 0.60% valeric acid, 0.20% caproic acid, 0.07% heptanoic acid, 0.02% caprylic acid, 0.005% capric acid, 0.003% lauric acid and 0.003% undecanoic acid) with different concentrations and 0.30% cinnamyl alcohol respectively act independently, and the bacteriostasis rate to candida albicans is less than 25%;
2. as can be seen from the results of the experiments in Table 15, groups 11-19: at a pH value of 3.8, 9 fatty acids (2.00% propionic acid, 2.2% butyric acid, 0.60% valeric acid, 0.20% caproic acid, 0.07% heptanoic acid, 0.02% caprylic acid, 0.005% capric acid, 0.003% lauric acid and 0.003% undecanoic acid) with different concentrations are respectively combined with 0.30% cinnamyl alcohol to have a strong bacteriostatic action or bacteriostatic action on the candida albicans, and the bacteriostatic rate is between 50 and 90% or more than 90%, which indicates that the combination of the two components has a synergistic bacteriostatic action on the candida albicans and the bacteriostatic action is enhanced.
Fourteen in vitro experiments
Basically according to the method of GB15979-2002 appendix C of sanitary Standard for Disposable sanitary articles, the bacteriostasis rate of the solution of different component combinations on Candida albicans ATCC10231 is studied for 20 minutes, wherein the percentage concentrations of the components are weight percentage concentration% (w/w), the pH values are 3.8, and the experimental results are shown in Table 16:
TABLE 16 bacteriostatic effect of different combinations of solutions on Candida albicans ATCC10231
Number of | Butyric acid (%) | Pimelic acid (%) | Phenethyl alcohol (%) | 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 |
The results show that:
1. as can be seen from the results of the experiments in Table 16, groups 1-3: when the pH value is 3.8, 1.00 percent of butyric acid, 1.00 percent of pimelic acid and 0.60 percent of phenethyl alcohol respectively and independently act, and the bacteriostasis rate to candida albicans is less than 10 percent;
2. as can be seen from table 16, set 4 experimental results: when the pH value is 3.8, the bacteriostasis rate of the solution of 1.00 percent butyric acid and 0.60 percent phenethyl alcohol to the candida albicans is 11.09 percent;
3. as can be seen from table 16, set 5 experimental results: when the pH value is 3.8, the solution of 1.00 percent of butyric acid, 1.00 percent of pimelic acid and 0.60 percent of phenethyl alcohol has the bacteriostatic action on the candida albicans, and the bacteriostatic rate is 65.22 percent.
In summary, it can be seen that: the solution of the combination of 1.00 percent pimelic acid, 1.00 percent butyric acid and 0.60 percent phenethyl alcohol has synergistic bacteriostatic action on candida albicans, and the bacteriostatic action is enhanced.
Experimental example fifteen
According to the method of appendix C of GB15979-2002 hygienic Standard for Disposable sanitary articles, experimental study is carried out to study the bacteriostasis of the combination solution of sodium propionate and dibasic acid/tribasic acid on Candida albicans ATCC10231 for 20 minutes, wherein the percentage concentration of each component is weight percentage concentration (w/w), and the pH value of the solution is 3.6. The results of the experiment are shown in table 17:
TABLE 17 bacteriostatic effect of solutions of different combinations of components on Candida albicans ATCC10231
The results show that:
1. as can be seen from the results of the experiments in sets 1-8 of Table 17: when the pH value is 3.6, 2.88% of sodium propionate, 7 kinds of dibasic acids or polybasic acids (4.38% of adipic acid, 3.54% of succinic acid, 4.02% of malic acid, 4.50% of tartaric acid, 3.50% of maleic acid, 5.76% of citric acid and 3.50% of fumaric acid) with different concentrations respectively act independently, and the bacteriostasis rate of the candida albicans is less than 25%;
2. as can be seen from table 17, set 9 of experimental results: when the pH value is 3.6, the solution of the combination of 1.25% sodium propionate and 4.38% adipic acid has the bacteriostatic action on the candida albicans, and the bacteriostatic rate is 72.46%;
3. as can be seen from the results of the experiments in groups 10-15 of Table 17: when the pH value is 3.6, the bacteriostasis rate of the solution of 1.25 percent sodium propionate and 6 kinds of dibasic acid or polybasic acid (3.54 percent succinic acid, 4.02 percent malic acid, 4.50 percent tartaric acid, 3.50 percent maleic acid, 5.76 percent citric acid and 3.50 percent fumaric acid) with different concentrations to the candida albicans is less than 25 percent.
In summary, it can be seen that: adipic acid and sodium propionate are combined, and the synergistic bacteriostatic effect on candida albicans is achieved.
Experimental example sixteen
According to the method of appendix C of GB15979-2002 hygienic Standard for Disposable sanitary articles, a basic antibacterial solution prepared by respectively combining citric acid, malic acid and succinic acid with 1.46% (w/w) adipic acid, 0.16% (w/w) sodium benzoate, 0.62% (w/w) propionic acid and 0.35% (w/w) phenethyl alcohol is studied, the basic antibacterial solution acts for 20 minutes and has an antibacterial effect on Candida albicans ATCC10231, wherein the percentage concentrations of the components are weight percentage concentrations% (w/w), the pH value of the basic antibacterial solution is 3.6, and the experimental results are shown in Table 18.
TABLE 18 influence of citric acid, malic acid, succinic acid on the bacteriostatic action
The results show that:
1. the basic antibacterial liquid has an antibacterial effect on candida albicans, and the antibacterial rate is 53.77%;
2. 1.00 percent of citric acid, 0.70 percent of malic acid and 0.61 percent of succinic acid are respectively added into the basic antibacterial liquid, and the antibacterial rates to candida albicans are 49.25 percent, 54.77 percent and 53.27 percent respectively.
In summary, it can be seen that: the citric acid, malic acid and succinic acid have no influence on the effect of the basic antibacterial liquid combined by 1.46% of adipic acid, 0.16% of sodium benzoate, 0.62% of propionic acid and 0.35% of phenethyl alcohol on the inhibition of candida albicans.
Seventeen in vitro experiments
Basically, according to the method in annex C of GB15979-2002 hygienic Standard for Disposable sanitary products, the bacteriostasis rate of the solution with different component combinations on Candida albicans ATCC10231 is studied for 20 minutes, wherein the percentage concentration of each component is weight percentage concentration (w/w), the pH value is 3.8, and the experimental results are shown in Table 19:
TABLE 19 bacteriostatic action of different combinations of solutions on Candida albicans ATCC10231
The results show that:
1. as can be seen from the results of the experiments in sets 1-9 of Table 19: when the pH value is 3.8, 7 fatty acids (1.32% butyric acid, 0.70% valeric acid, 0.20% caproic acid, 0.12% enanthic acid, 0.03% caprylic acid, 0.0075% pelargonic acid, 0.005% capric acid) with different concentrations and 2 dibasic acids (1.50% adipic acid and 2.00% pimelic acid) with different concentrations respectively act independently, and the bacteriostasis rate to candida albicans is less than 35%;
2. as can be seen from the results of the experiments in groups 10-16 of Table 19: when the pH value is 3.8, solutions of 7 fatty acids (1.32% of butyric acid, 0.70% of valeric acid, 0.20% of caproic acid, 0.12% of enanthic acid, 0.03% of caprylic acid, 0.0075% of pelargonic acid and 0.005% of capric acid) with different concentrations and 1.50% of adipic acid respectively have a strong bacteriostatic action or bacteriostatic action on candida albicans, and the bacteriostatic rate is between 50% and 90% or is more than 90%;
3. as can be seen from the results of the 17 th to 23 rd groups of experiments in Table 19: when the pH value is 3.8, solutions of 7 fatty acids (1.32% of butyric acid, 0.70% of valeric acid, 0.20% of caproic acid, 0.12% of heptanoic acid, 0.03% of caprylic acid, 0.0075% of pelargonic acid and 0.005% of capric acid) with different concentrations and 2.00% of pimelic acid respectively have a strong bacteriostatic action or bacteriostatic action on candida albicans, and the bacteriostatic rate is between 50% and 90% or is more than 90%.
In summary, it can be seen that: at a pH value of 3.8, solutions of 7 fatty acids (1.32% butyric acid, 0.70% valeric acid, 0.20% caproic acid, 0.12% enanthic acid, 0.03% caprylic acid, 0.0075% pelargonic acid, 0.005% capric acid) with different concentrations, respectively, combined with 1.50% adipic acid and 2.00% pimelic acid, have a synergistic bacteriostatic effect on Candida albicans, and all enhance the bacteriostatic effect.
Eighteen in vitro experiments
Basically according to the method of GB15979-2002 appendix C of sanitary Standard for Disposable sanitary articles, the antibacterial rate of a solution of different component combinations on Escherichia coli ATCC25922, staphylococcus aureus ATCC6538 and Candida albicans ATCC10231 is studied for 20 minutes, wherein the percentage concentrations of the components are weight percentage concentration% (w/w), the pH values are 3.8, and the experimental results are shown in Table 20:
TABLE 20 bacteriostatic action of different solutions on Escherichia coli, staphylococcus aureus and Candida albicans
As can be seen from the experimental results of table 20: when the pH value is 3.8, 9 fatty acids (3.00% of butyric acid, 0.45% of caproic acid, 0.30% of heptanoic acid, 0.05% of caprylic acid, 0.03% of pelargonic acid, 0.008% of capric acid, 0.006% of undecanoic acid, 0.006% of undecylenic acid and 0.006% of lauric acid) and 5.00% of pimelic acid with different concentrations respectively act independently, have a strong bacteriostatic action or bacteriostatic action on candida albicans, and the bacteriostatic rate is between 50% and 90% or more than 90%; has strong bacteriostatic action on Escherichia coli and Staphylococcus aureus, and the bacteriostatic rate is 100.00 percent.
Nineteen in vitro experiments
According to the method of annex C of GB15979-2002 hygienic Standard for Disposable sanitary articles, the antibacterial effect of the aqueous solution of different component combinations on Candida albicans ATCC10231 is researched for 20 minutes, wherein the percentage concentration of each component is weight percentage concentration% (w/w), and the pH value is 3.8. The results of the experiment are shown in table 21:
TABLE 21 bacteriostatic effect of different solutions on Candida albicans ATCC10231
Number of | Propionic acid (%) | Pimelic acid (%) | Cinnamyl 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 |
The results show that:
1. as can be seen from table 21, set 1 experimental results: when the pH value is 3.8, the bacteriostasis rate of the solution of 1.50 percent pimelic acid, 0.20 percent sodium benzoate and 2.00 percent propionic acid on the candida albicans is 41.25 percent;
2. as can be seen from the results of the experiments in sets 2-4 of Table 21: when the pH value is 3.8, the solution of 0.03-0.08% cinnamyl alcohol, 1.50% pimelic acid, 0.20% sodium benzoate and 2.00% propionic acid has strong bacteriostatic action or bacteriostatic action on candida albicans, and the bacteriostatic rate is 50-90% or more than 90%.
In summary, 0.03-0.08% cinnamyl alcohol has significant effect on the effect of the solution of 1.50% pimelic acid, 0.20% sodium benzoate and 2.00% propionic acid on inhibiting candida albicans, and the bacteriostatic effect is enhanced.
Twenty vitro experiments
According to the method of annex C of GB15979-2002 hygienic Standard for Disposable sanitary articles, the antibacterial effect of the aqueous solution of different component combinations on Candida albicans ATCC10231 is researched for 20 minutes, wherein the percentage concentration of each component is weight percentage concentration% (w/w), and the pH value is 4.8. The results of the experiment are shown in table 22:
TABLE 22 bacteriostatic effect of different solutions on Candida albicans ATCC10231
Numbering | Propionic acid (%) | Pimelic acid (%) | Sodium benzoate (%) | Bacteriostatic ratio (%) |
1 | -- | 5.00 | -- | 15.42 |
2 | -- | -- | 1.18 | 15.92 |
3 | 0.10 | -- | -- | 2.90 |
4 | 0.10 | 5.00 | 1.18 | 61.02 |
The results show that:
1. as can be seen from the results of the experiments in Table 22, groups 1-3: when the pH value is 4.8, 5.00 percent of pimelic acid, 1.18 percent of sodium benzoate and 0.10 percent of propionic acid respectively act independently, and the bacteriostasis rate to candida albicans is lower than 20 percent;
2. as can be seen from table 22, set 4 experimental results: when the pH value is 4.8, the combined solution of 5.00 percent pimelic acid, 1.18 percent sodium benzoate and 0.10 percent propionic acid has the bacteriostatic action on the candida albicans, and the bacteriostatic rate is 61.02 percent.
In summary, at a pH of 4.8, a solution of a combination of three components, i.e., pimelic acid 5.00%, sodium benzoate 1.18%, and propionic acid 0.10%, has a synergistic bacteriostatic effect on candida albicans, and the bacteriostatic effect is enhanced.
Twenty one in vitro experiment
According to the method of appendix C of GB15979-2002 hygienic Standard for Disposable sanitary articles, the antibacterial effect of aqueous solutions of different component combinations on Escherichia coli ATCC25922 and Staphylococcus aureus ATCC6538 is studied for 20 minutes, wherein the percentage concentrations of the components are weight percentage concentration% (w/w), and the pH value is 4.0. The results of the experiment are shown in table 23:
TABLE 23 bacteriostatic effect of different solutions on Escherichia coli ATCC25922 and Staphylococcus aureus ATCC6538
The results show that:
1. as can be seen from the results of the experiments in sets 1-4 of Table 23: when the pH value is 4.0, a solution of 0.06% sodium benzoate respectively combined with 0.30% phenethyl alcohol, 0.50% propionic acid, 0.45% butyric acid and 0.06% caproic acid has an antibacterial effect on Escherichia coli and staphylococcus aureus, and the antibacterial rate is higher than 50%;
2. as can be seen from the results of the 5 th to 7 th sets of experiments in Table 23: when the pH value is 4.0, the solution of 0.30 percent of phenethyl alcohol, 0.50 percent of propionic acid, 0.45 percent of butyric acid and 0.06 percent of caproic acid which are respectively combined has the bacteriostasis to Escherichia coli and staphylococcus aureus, and the bacteriostasis rate is higher than 50 percent;
3. as can be seen from the results of the experiments in sets 8-10 of Table 23: when the pH value is 4.0, the solution of the combination of sodium benzoate with 0.045%, phenethyl alcohol with 0.30% and propionic acid with 0.35% has the bacteriostatic action on Escherichia coli and staphylococcus aureus, and the bacteriostatic rate is higher than 50%; the solution of 0.045% sodium benzoate and 0.30% phenethyl alcohol which are respectively combined with 0.30% butyric acid and 0.06% caproic acid has strong bacteriostatic action on Escherichia coli and staphylococcus aureus, and the bacteriostatic rate is higher than 90%;
4. as can be seen from the results of the 11 th to 13 th sets of experiments in Table 23: at a pH value of 4.0, solutions of 1.50% of adipic acid, 0.045% of sodium benzoate and 0.30% of phenethyl alcohol which are respectively combined with 3 kinds of fatty acids (0.35% of propionic acid, 0.30% of butyric acid and 0.06% of caproic acid) with different concentrations have strong bacteriostatic action on Escherichia coli, the bacteriostatic rate is higher than 90%, the bacteriostatic action on staphylococcus aureus is between 50% and 90%.
Twenty two in vitro experiments
According to the method of appendix C of GB15979-2002 hygienic Standard for Disposable sanitary articles, the antibacterial effect of the aqueous solution of different component combinations on Candida albicans ATCC10231 is studied for 20 minutes, wherein the percentage concentration of each component is weight percentage concentration% (w/w). The results of the experiment are shown in table 24:
TABLE 24 bacteriostatic effect of different solutions on Candida albicans ATCC10231
As can be seen from the results of the experiments in sets 1-3 of 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% phenethyl alcohol has bacteriostasis to candida albicans when the pH values are 4.0 and 4.2 respectively, the bacteriostasis rates are 86.56% and 66.74% respectively, and the bacteriostasis rate of the combined solution to candida albicans is 37.61% when the pH value is 4.4 respectively.
In summary, it can be seen that: the lower the pH value of 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% phenethyl alcohol, the stronger the bacteriostatic action on Candida albicans.
Twenty three in vitro experiments
According to the method of appendix C of GB15979-2002 hygienic Standard for Disposable sanitary articles, the antibacterial effect of the aqueous solution of different component combinations on Candida albicans ATCC10231 is studied for 20 minutes, wherein the percentage concentration of each component is weight percentage concentration% (w/w), and the pH value of the solution is 3.86. The results of the experiment are shown in table 25:
TABLE 25 bacteriostatic effects of different solutions on Candida albicans ATCC10231
The results show that:
1. as can be seen from table 25, set 1 experimental results: when the pH value is 3.86, the combined solution of 1.46% adipic acid, 0.20% malic acid, 0.12% sodium benzoate, 0.20% propionic acid, 0.45% butyric acid, 0.30% phenethyl alcohol and 1.80% palatinose has an antibacterial effect on candida albicans, and the antibacterial rate is 75.14%;
2. as can be seen from the experimental results of group 2 of table 25: when the pH value is 3.86, the combined solution of 1.46 percent of adipic acid, 0.20 percent of malic acid, 0.12 percent of sodium benzoate, 0.20 percent of propionic acid, 0.45 percent of butyric acid, 0.30 percent of phenethyl alcohol, 1.80 percent of palatinose and 0.04 percent of puerarin has the bacteriostatic action on candida albicans, and the bacteriostatic rate is 78.45 percent;
3. as can be seen from table 25, set 3 experimental results: when the pH value is 3.86, the combined solution of 1.46 percent of adipic acid, 0.20 percent of malic acid, 0.12 percent of sodium benzoate, 0.20 percent of propionic acid, 0.45 percent of butyric acid, 0.30 percent of phenethyl alcohol, 1.80 percent of palatinose and 0.06 percent of puerarin has the bacteriostatic action on the candida albicans, and the bacteriostatic rate is 76.24 percent.
In conclusion, when the pH value of the solution is 3.86, the puerarin in the amounts of 0.04% and 0.06% has no influence on the inhibition effect of the candida albicans, and the bacteriostasis effect is not weakened. .
It will be appreciated that other estrogenic substances, such as diethylstilbestrol, hexestrol, estradiol, estrone, estriol, nilestriol, ethinylestradiol cyclopentylether, ethinylestriol, promestrene, and other phytoestrogens, such as daidzin, daidzein, glycitein, puerarin, coumestrol, equol, apine, genistin, genistein, biochanin, coumestrol, formononetin, resveratrol, secoisolariciresinol, lignan, and lignan, have properties and principles similar to those of puerarin, and thus it is contemplated that the aforementioned estrogenic and phytoestrogens do not significantly reduce the inhibitory effect of the composition on candida albicans.
Twenty four in vitro experiments
According to the method of appendix C of GB15979-2002 hygienic Standard for Disposable sanitary articles, the antibacterial effect of the aqueous solution of different component combinations on Candida albicans ATCC10231 is studied for 20 minutes, wherein the percentage concentration of each component is weight percentage concentration% (w/w), and the pH value is 4.0. The results are shown in table 26:
TABLE 26 bacteriostatic action of different solutions on Candida albicans ATCC10231
The results show that:
comparing the results of the experiments in groups 1 and 2 in table 26, it can be seen that: at a pH of 4.0, 0.55% glutamic acid had no effect on the inhibition of Candida albicans by a solution of the combination "0.14% malic acid, 1.46% adipic acid, 0.20% sodium benzoate, 1.67% propionic acid, 0.40% phenethyl alcohol".
It will be appreciated that other suitable amino acids, such as glutamine, L-aspartic acid, asparagine, leucine, isoleucine, phenylalanine, valine, proline, threonine, have properties and principles of action similar to that of glutamic acid, and thus it is also contemplated that the aforementioned amino acids do not affect the Candida albicans inhibitory effect of the composition.
Twenty five of in vitro experiments
According to the method of appendix C of GB15979-2002 hygienic Standard for Disposable sanitary articles, the antibacterial effect of aqueous solutions of different component combinations on Escherichia coli ATCC25922 and Staphylococcus aureus ATCC6538 is studied for 20 minutes, wherein the percentage concentrations of the components are weight percentage concentration% (w/w), and the pH value is 3.8. The results of the experiment are shown in table 27:
TABLE 27 bacteriostatic action of different solutions on Escherichia coli ATCC25922 and Staphylococcus aureus ATCC6538
The results show that:
1. as can be seen from the results of the experimental groups 1-4 of Table 27: when the pH value is 3.8, the solution of 1.75 percent of adipic acid respectively combined with 1.50 percent of propionic acid, 1.30 percent of butyric acid, 0.50 percent of valeric acid and 0.20 percent of caproic acid has strong bacteriostatic action on Escherichia coli, the bacteriostatic rates of the solutions are all 100.00 percent, and the solution has strong bacteriostatic action or bacteriostatic action on staphylococcus aureus, and the bacteriostatic rate is between 50 percent and 90 percent or more than 90 percent;
2. as can be seen from the results of the 5 th to 8 th sets of experiments in Table 27: when the pH value is 3.8, the solution of 0.03 percent of cinnamyl alcohol and 1.75 percent of adipic acid respectively combined with 1.50 percent of propionic acid, 1.30 percent of butyric acid, 0.50 percent of valeric acid and 0.20 percent of caproic acid has strong bacteriostatic action on Escherichia coli and staphylococcus aureus, and the bacteriostatic rate is 100.00 percent;
3. as can be seen from the results of the 9 th to 12 th sets of experiments in Table 27: when the pH value is 3.8, the solution of 0.03 percent of cinnamic acid and 1.75 percent of adipic acid respectively combined with 1.50 percent of propionic acid, 1.30 percent of butyric acid, 0.50 percent of valeric acid and 0.20 percent of caproic acid has strong bacteriostatic action on Escherichia coli and staphylococcus aureus, and the bacteriostatic rate is 100.00 percent.
Twenty-six in vitro experiments
The bacteriostatic action of each bacteriostatic agent in the composition on staphylococcus aureus, pseudomonas aeruginosa, escherichia coli, candida albicans and aspergillus niger was studied with reference to the method of the bacteriostatic efficacy test method and the result judgment standard of the fourth 1121 of the pharmacopoeia of the people's republic of China, 2020 edition, and the experimental results are shown in table 28.
TABLE 28 compositions 1 Experiment of bacteriostatic efficacy
Note:
1. the composition comprises: 1.50% (w/w) adipic acid, 0.14% (w/w) sodium benzoate, 0.32% (w/w) phenethyl alcohol, 0.54% (w/w) propionic acid, 0.20% (w/w) hexanoic acid, 0.20% (w/w) palatinose, 0.60% (w/w) maltose, 0.0005% (w/w) rose essential oil, 2.15% (w/w) xanthan gum
2. The difference between the lg value of the number of bacteria measured at each interval and the lg value of the number of bacteria inoculated in 1ml (g) of the test sample
3. Not increased means that the amount of the test bacteria increased by not more than 0.5lg for the previous measurement time
From the results of the experiment in table 28, it can be seen that: when the pH value is 4.2, the lg value of each experimental bacterium which is reduced by 14 days relative to the bacterium concentration added by 0 day is 5, and the lg value which is reduced by 28 days relative to 14 days is not increased, so that the requirement is met; therefore, the composition with the pH value of 4.2 in the experiment has the preservative effect.
It is worth noting that even though the experimental conditions, methods and the like are all the same, due to experimental errors, the results of in vitro bacteriostasis experiments, such as bacteriostasis rate, still have differences when the experiments are repeated, but the differences are reasonable and can be understood by those skilled in the art. Thus, the data of the present disclosure controls in vitro experimental data of the present disclosure if there is inconsistency with the data in the prior application.
In vivo experiment 1
The 3 groups of gels containing different components are administrated in the vagina of the cynomolgus monkey 1 time a day and 0.5 ml each time for 5 days continuously, the vaginal swab is taken to measure the pH value and smear stauroscopy, the influence of the gel on the pH value of the vaginal secretion of the cynomolgus monkey and the vaginal flora is observed, and the experimental results are shown in a table 29:
TABLE 29 Effect of different compositions of the bacteriostatic gels on cynomolgus monkey vaginal acidity and flora
Note:
1: group B gels 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) phenethyl alcohol, 1.00% (w/w) citric acid, 1.168% (w/w) adipic acid, 2.15% (w/w) xanthan gum, adjusted to pH 3.6
2: group C gels 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) phenethyl alcohol, 0.61% (w/w) succinic acid, 1.168% (w/w) adipic acid, 2.15% (w/w) xanthan gum, adjusted to pH 3.6
3: group 2 gels containing 1.15% (w/w) sodium propionate, 0.45% (w/w) phenethyl alcohol, 0.20% (w/w) sodium benzoate, 1.50% (w/w) maltose, 1.00% (w/w) citric acid, 2.15% (w/w) xanthan gum, adjusted to pH 3.6
4: nugent scores are microscopic examination after vaginal secretion smear and gram staining, and scores are carried out according to staining, morphology and quantity of bacteria, and specifically comprise the following steps:
the number of the vaginal bacteria is more than or equal to 7, the vaginal bacteria mainly comprise gram negative bacilli and/or negative cocci and positive cocci, and large positive bacilli are absent or extremely few;
4-6 points, the vaginal bacteria mainly comprise gram negative bacilli and/or negative cocci and/or positive cocci, and the gram positive bacilli are less;
0-3 points, normal vaginal flora, and large gram-positive bacilli as main bacteria.
The results show that:
1. from the results of the experiment in group B of Table 29, it can be seen that: 3 cynomolgus monkey vaginal secretion pH value is reduced to 3.8 and vaginal flora Nugent score is reduced to 0-3 when 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) phenethyl alcohol, 1.00% (w/w) citric acid, 1.168% (w/w) adipic acid and 2.15% (w/w) xanthan gum' is applied for 5 times;
2. from the results of the experiment in group C of table 29, it can be seen that: 3 cynomolgus monkey vaginal secretion pH values are all reduced to 3.8 after 5 times of application of 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) phenethyl alcohol, 0.61% (w/w) succinic acid, 1.168% (w/w) adipic acid and 2.15% (w/w) xanthan gum', the vaginal flora Nugent scores 3, 1 of 3 cynomolgus monkeys is reduced to 0-3 minutes, and 2 is reduced to 4-6 minutes;
3. from the results of the experiment in group 2 of table 29, it can be seen that: the pH value is 3.6, and the gel containing 1.15% (w/w) sodium propionate, 0.45% (w/w) phenethyl 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 is applied for 5 times, 3 vaginal secretion pH values in 5 cynomolgus monkeys are reduced to 3.8,1 and 4.4,1 only due to menstrual shedding; the Nugent score of vaginal flora 3 were reduced to 0-3 points, 1 was still > 7 points, and 1 was due to menstrual drop.
In conclusion, 3 groups of gels with the pH value of 3.6 in the experiment have the effects of inhibiting abnormal vaginal flora, recovering vaginal acidity and recovering lactobacillus vaginalis, the effect of the group B in 2 groups of gels (B, C group) containing adipic acid and respectively containing citric acid and succinic acid is better than that of the group C and the group 2 gels without adipic acid, and the effect of the group 2 gels without adipic acid in inhibiting abnormal vaginal flora, recovering vaginal acidity and recovering lactobacillus vaginalis is the weakest in the three groups of gels.
In vivo experiment 2
The 3 groups of gels containing different components are administrated in the vagina of the rhesus monkey for 5 days continuously with 1 time per day and 0.5 ml per time, the vaginal secretion is taken to measure the pH value and smear staphyloscopy, the influence of the gel on the pH value of the vaginal secretion of the rhesus monkey and vaginal flora is observed, and the experimental results are shown in table 30:
TABLE 30 Effect of different component containing bacteriostatic gels on vaginal acidity and flora of rhesus monkeys
Note:
1: group A gel containing 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) phenethyl alcohol, 0.35% (w/w) malic acid, 2.15% (w/w) xanthan gum, adjusted to pH 4.1
2: group B gels containing 2.00% (w/w) isomaltulose, 0.12% (w/w) sodium benzoate, 0.60% (w/w) butyric acid, 0.0010% (w/w) capric acid, 1.31% (w/w) adipic acid, 0.30% (w/w) phenethyl alcohol, 0.35% (w/w) malic acid, 2.15% (w/w) xanthan gum, adjusted to pH 4.1
3: group C gels containing 2.00% (w/w) isomaltulose, 0.12% (w/w) sodium benzoate, 0.60% (w/w) butyric acid, 0.0015% (w/w) capric acid, 1.31% (w/w) adipic acid, 0.30% (w/w) phenethyl alcohol, 0.35% (w/w) malic acid, 2.15% (w/w) xanthan gum, adjusted to pH 4.1
4: note 4 of in vivo experiment I
The results show that:
1. from the experimental results in group a, it can be seen that: gel with pH value of 4.1 and containing 1.31% (w/w) adipic acid, 0.35% (w/w) malic acid, 0.30% (w/w) phenethyl alcohol, 0.12% (w/w) sodium benzoate, 0.60% (w/w) butyric acid, 2.00% (w/w) isomaltulose and 2.15% (w/w) xanthan gum, the gel is applied for 5 times, pH values of vaginal secretions of 3 rhesus monkeys are all reduced to 3.8, and Nugent scores of vaginal flora are all reduced to 0-3 points; the pH value of the vaginal secretion of 1 rhesus monkey is still 5.4, and the Nugent score of the vaginal flora is reduced to 4-6.
2. From the experimental results in group B it can be seen that: gel of pH 4.1 containing "1.31% (w/w) adipic acid, 0.35% (w/w) malic acid, 0.30% (w/w) phenethyl alcohol, 0.12% (w/w) sodium benzoate, 0.60% (w/w) butyric acid, 0.0010% (w/w) capric acid", and 2.00% (w/w) isomaltulose, 2.15% (w/w) xanthan gum, using 5 times, 3 of 5 rhesus monkeys had their vaginal secretion pH reduced to 3.8, vaginal flora Nugent score reduced to 0-3 min; the pH value of the vaginal secretion of 1 vaginal is reduced to 4.1, and the Nugent score of the vaginal flora is reduced to 4-6 points; the pH of the vaginal secretion of 1 patient was still 5.4, and the Nugent score of vaginal flora was reduced to 4-6 points.
3. From the results of the experiment in group C: 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) phenethyl alcohol, 0.12% (w/w) sodium benzoate, 0.60% (w/w) butyric acid, 0.0015% (w/w) capric acid", and 2.0% (w/w) isomaltulose, 2.15% (w/w) xanthan gum, using 5 times, the pH of 1 vaginal secretion in 2 rhesus monkeys was reduced to 3.8, the nucent score for vaginal flora was reduced to 0-3 min; the pH of another 1 vaginal secretion dropped to 4.1, and the Nugent score of vaginal flora dropped to 4-6.
In conclusion, the components of the experiment respectively comprise three groups of gels of 0.60% (w/w) butyric acid, 0.00125% (w/w) capric acid and 0.0015% (w/w) capric acid, and the three groups of gels have the effects of inhibiting abnormal vaginal flora, regulating vaginal flora, recovering lactobacillus vaginalis and recovering normal vaginal acidity.
Experiment in vivo
The 5 gel groups containing different components are administrated in the vagina of the cynomolgus monkey 1 time a day and 0.5 ml each time for 5 days continuously, the vaginal swab is taken to measure the pH value and smear stauroscopy, the influence of the gel on the pH value of the vaginal secretion of the cynomolgus monkey and the vaginal flora is observed, and the experimental results are shown in a table 31:
TABLE 31 Effect of different component containing bacteriostatic gels on cynomolgus monkey vaginal acidity and flora
Note:
1: group 1 gels containing 0.14% (w/w) sodium benzoate, 0.54% (w/w) propionic acid, 1.46% (w/w) adipic acid, 0.30% (w/w) phenethyl alcohol, 0.35% (w/w) malic acid, 2.15% (w/w) xanthan gum, adjusted to pH 3.8
2: group 2 gels containing 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) phenethyl alcohol, 0.35% (w/w) malic acid, 2.15% (w/w) xanthan gum, adjusted to pH 3.8
3: group 3 gels containing 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) phenethyl alcohol, 0.35% (w/w) malic acid, 2.15% (w/w) xanthan gum, adjusted to pH 3.8
4: group 4 gels containing 2.00% (w/w) isomaltulose, 0.12% (w/w) sodium benzoate, 0.38% (w/w) propionic acid, 1.31% (w/w) adipic acid, 0.0015% (w/w) decanoic acid, 0.30% (w/w) phenethyl alcohol, 0.35% (w/w) malic acid, 2.15% (w/w) xanthan gum, adjusted to pH 3.9
5: group 5 gels containing 2.00% (w/w) isomaltulose, 0.12% (w/w) sodium benzoate, 0.38% (w/w) propionic acid, 1.31% (w/w) adipic acid, 0.01% (w/w) octanoic acid, 0.30% (w/w) phenethyl alcohol, 0.35% (w/w) malic acid, 2.15% (w/w) xanthan gum, adjusted to pH 3.9
6: note 4 of in vivo experiment I
The results show that:
1. from the results of the experiments in groups 1 to 3 of table 31, it can be seen that: group 1 gels without sugar, group 2 gels with 2.00% (w/w) maltose, group 3 gels with 2.00% (w/w) isomaltulose, the other components of group 3 gels except the sugar component being identical, all having a pH of 3.8 and all containing "0.14% (w/w) sodium benzoate, 0.54% (w/w) propionic acid, 1.46% (w/w) adipic acid, 0.30% (w/w) phenethyl alcohol, 0.35% (w/w) malic acid, 2.15% (w/w) xanthan gum".
The medicine is taken for 3 times, and the pH value of vaginal secretion is reduced to 4.1 or below in 3 groups; vaginal flora Nugent scores, two of 4 cynomolgus monkeys of group 1 without sugar are reduced to 4-6 points, and two are reduced to 0-3 points; the number of 2 cynomolgus monkeys in group 2 containing maltose decreased to 0-3 points; 2 out of 3 cynomolgus monkeys of group 3 containing isomaltulose dropped to 0-3 points and 1 dropped to 4-6 points.
2. From the results of the 4 th set of experiments in table 31, it can be seen that: the gel containing the pH value of 3.9, 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) phenethyl alcohol, 0.35% (w/w) malic acid, 0.0015% (w/w) capric acid and 2.15% (w/w) xanthan gum is applied for 5 times, the pH value of the vaginal secretion of 2 cynomolgus monkeys is reduced to 3.8, the Nugent score of vaginal flora is reduced to 0-3, and the other 1 cynomolgus monkey is reduced to 4-6.
3. From table 31, set 5 experimental results it can be seen that: 3 times of 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) phenethyl alcohol, 0.35% (w/w) malic acid, 0.01% (w/w) octanoic acid and 2.15% (w/w) xanthan gum', the pH value of the vaginal secretion of 2 cynomolgus monkeys is reduced to 3.8, and the Nugent score of the vaginal flora is reduced to 0-3 minutes.
In summary, it can be seen that:
1. the gel which is at the pH value of 3.8 and contains the combination of 1.46% (w/w) adipic acid, 0.35% (w/w) malic acid, 0.54% (w/w) propionic acid, 0.30% (w/w) phenethyl alcohol and 0.14% (w/w) sodium benzoate and does not contain sugar in the experiment has the effects of inhibiting abnormal vaginal flora, recovering vaginal acidity and recovering vaginal lactobacilli, as shown in the experiment result of the group 1. However, the gels of groups 2 and 3, which further contained maltose or isomaltulose, had a faster and stronger action of restoring vaginal lactobacilli than the gel of group 1, which did not contain sugar, as shown by the results of experiments of groups 2 and 3.
2. The pH value of the test is 3.9, and the gel respectively containing 1.31% (w/w) adipic acid, 0.35% (w/w) malic acid, 0.38% (w/w) propionic acid, 0.30% (w/w) phenethyl alcohol, 0.12% (w/w) sodium benzoate and 2.0% (w/w) isomaltulose has the effects of inhibiting abnormal vaginal flora, restoring vaginal acidity and restoring lactobacillus vaginalis, as shown by the results of the experiments in groups 4 and 5.
Experiment in vivo
The 3 groups of gels containing different components are administrated in the vagina of the cynomolgus monkey 1 time a day and 0.5 ml each time for 5 days continuously, the vaginal swab is taken to measure the pH value and smear stauroscopy, the influence of the gel on the pH value of the vaginal secretion of the cynomolgus monkey and the vaginal flora is observed, and the experimental results are shown in a table 32:
TABLE 32 Effect of different compositions of the bacteriostatic gels on cynomolgus monkey vaginal acidity and flora
Note:
1: group 1 gels containing 2.00% (w/w) isomaltulose, 0.12% (w/w) sodium benzoate, 0.38% (w/w) propionic acid, 1.31% (w/w) adipic acid, 0.04% (w/w) heptanoic acid, 0.30% (w/w) phenethyl alcohol, 0.35% (w/w) malic acid, 2.15% (w/w) xanthan gum, adjusted to pH 3.9
Note 2: group 2 gels containing 2.00% (w/w) isomaltulose, 0.12% (w/w) sodium benzoate, 0.38% (w/w) propionic acid, 1.31% (w/w) adipic acid, 0.10% (w/w) hexanoic acid, 0.30% (w/w) phenethyl alcohol, 0.35% (w/w) malic acid, 2.15% (w/w) xanthan gum, adjusted to pH 3.9
Note 3: group 3 gels containing 2.00% (w/w) isomaltulose, 0.12% (w/w) sodium benzoate, 0.38% (w/w) propionic acid, 1.31% (w/w) adipic acid, 0.20% (w/w) valeric acid, 0.30% (w/w) phenethyl alcohol, 0.35% (w/w) malic acid, 2.15% (w/w) xanthan gum, adjusted to pH 3.9
Note 4: note 4 from in vivo experiment one
The results show that:
1. as can be seen from table 32, group 1 experimental results: the pH value is 3.9, and the 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) phenethyl alcohol, 0.35% (w/w) malic acid, 0.04% (w/w) heptanoic acid and 2.15% (w/w) xanthan gum is applied for 5 times, the pH value of the vaginal secretion of the cynomolgus monkey is reduced to 3.8, and the Nugent score of the vaginal flora is reduced to 0-3.
2. From table 32, set 2 experimental results, it can be seen that: 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) phenethyl alcohol, 0.35% (w/w) malic acid, 0.10% (w/w) hexanoic acid, 2.15% (w/w) xanthan gum" at a pH of 3.9, the pH of vaginal secretions of 2 cynomolgus monkeys decreased to 4.1 or below, and the vaginal flora Nugent score decreased to 0-3 points, for 5 administrations.
3. From table 32, set 3 experimental results it can be seen that: a gel 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) phenethyl alcohol, 0.35% (w/w) malic acid, 0.20% (w/w) valeric acid, 2.15% (w/w) xanthan gum" was administered 5 times, the pH of the vaginal secretions of 2 cynomolgus monkeys remained 5.4, the vaginal flora Nugent score of 1 cynomolgus monkey dropped to 0-3 minutes, and another 1 cynomolgus monkey dropped to 4-6 minutes.
As can be seen from the above, 3 groups of gels having a pH of 3.9 and 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) phenethyl alcohol, 0.35% (w/w) malic acid" and containing 0.04% (w/w) heptanoic acid, 0.10% (w/w) hexanoic acid, 0.20% (w/w) valeric acid, 2.15% (w/w) xanthan gum, respectively, have the effects of inhibiting abnormal vaginal flora and restoring lactobacillus vaginalis. Group 2 gels containing 0.04% (w/w) heptanoic acid and 0.10% (w/w) hexanoic acid, respectively, also have the effect of restoring vaginal acidity.
Experiment in vivo five
The 6 gel groups containing different components are administrated in the vagina of the cynomolgus monkey for 5 days continuously by 1 time per day and 0.5 ml per time, a vaginal swab is taken to test the pH value and smear stauroscopy, the influence of the gel on the pH value of the vaginal secretion of the cynomolgus monkey and the vaginal flora is observed, and the experimental results are shown in a table 33:
TABLE 33 Effect of different component bacteriostatic gels on cynomolgus monkey vaginal acidity and flora
Note:
1: group 1 gels containing 0.10% (w/w) hexanoic acid, 1.50% (w/w) adipic acid, 2.00% (w/w) maltose, 2.15% (w/w) xanthan gum, adjusted to pH 3.1
2: gel group 2 contained 2.00% (w/w) propionic acid, 0.30% (w/w) cinnamyl alcohol, 0.60% (w/w) succinic acid, 2.00% (w/w) maltose, 2.15% (w/w) xanthan gum, and pH was adjusted to 3.8
3: group 3 gels containing 0.02% (w/w) caprylic acid, 0.25% (w/w) benzoic acid, 1.00% (w/w) citric acid, 2.00% (w/w) maltose, 2.15% (w/w) xanthan gum, pH adjusted to 3.8
4: group 4 gels contained 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, 2.15% (w/w) xanthan gum, adjusted to pH 3.80
5: group 5 gels contained 0.20% (w/w) benzoic acid, 0.50% (w/w) propionic acid, 1.50% (w/w) adipic acid, 2.00% (w/w) maltose, 2.15% (w/w) xanthan gum, and pH adjusted to 3.8
6: group 6 gels containing 1.00% (w/w) pimelic acid, 0.60% (w/w) phenethyl alcohol, 1.25% (w/w) butyric acid, 2.00% (w/w) maltose, 2.15% (w/w) xanthan gum, adjusted to pH 3.8
7: note 4 from in vivo experiment one
The results show that:
1. as can be seen from table 33, set 1 experimental results: the pH value is 3.1, a 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 is applied for 5 times, 1 of 3 cynomolgus monkeys stops the experiment due to menstruation, the pH values of the rest 2 vaginal secretions are still 5.4, the other vaginal secretions are reduced to 3.8, the vaginal flora Nugent score is reduced to 4-6 points by 1, and the other vaginal flora Nugent score is reduced to 0-3 points;
2. as can be seen from table 33, set 2 experimental results: a gel with a pH value of 3.8 and 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 is taken 5 times, the pH value of 1 vaginal secretion in 2 cynomolgus monkeys is reduced to 4.1,1 which is still 5.4, the vaginal flora Nugent score is reduced to 4-6 points and 1 vaginal flora is reduced to 0-3 points;
3. as can be seen from table 33, set 3 experimental results: the pH value is 3.8, the medicine contains 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, the medicine is taken for 5 times, and the pH value of vaginal secretion of 2 cynomolgus monkeys is reduced from 1 to 3.8,1 to 4.1; the Nugent scores of the vaginal flora are reduced to 0-3 points;
4. from table 33, set 4 experimental results it can be seen that: the pH value of the vaginal secretion of 2 cynomolgus monkeys is 3.8, and the pH value of the vaginal secretion of the 2 cynomolgus monkeys is 1 to 4.6 and 1 to 3.8 after 5 times of medication of 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 Nugent score of the vaginal flora is reduced to 4-6 points for 1, and is reduced to 0-3 points for 1;
5. as can be seen from table 33, set 5 experimental results: the pH value is 3.8, the medicine contains 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, the pH value of vaginal secretion in 2 cynomolgus monkeys is reduced to 4.6, and 1 cynomolgus monkey is reduced to 3.8 after 5 times of medication; the Nugent score of the vaginal flora is reduced to 4-6 points for 1, and is reduced to 0-3 points for 1;
6. from table 33, set 6 experimental results it can be seen that: the pH value is 3.8, and the pH value of vaginal secretion in 2 cynomolgus monkeys is reduced to 3.8 and 1 cynomolgus monkeys is reduced to 4.1 after the drug is taken for 5 times, wherein the drug contains 1.00% (w/w) pimelic acid, 0.60% (w/w) phenethyl alcohol, 1.25% (w/w) butyric acid, 2.00% (w/w) maltose and 2.15% (w/w) xanthan gum; the Nugent score of vaginal flora is reduced to 0-3 points for 1, and 4-6 points for 1.
In summary, it can be seen that: the composition gel of the above 6 has effects of inhibiting vaginal abnormal flora, recovering vaginal acidity, and recovering vaginal Lactobacillus.
Experiment in vivo six
The gel containing adipic acid and fumaric acid in the components is administrated in the vagina of the cynomolgus monkey for 5 days continuously for 1 time and 0.5 ml each time every day, a vaginal swab is taken to test the pH value and smear stauroscopy, the influence of the gel on the pH value of the vaginal secretion of the cynomolgus monkey and the vaginal flora is observed, and the experimental result is shown in a table 34:
TABLE 34 Effect of adipic acid and fumaric acid containing gels on cynomolgus monkey vaginal acidity and flora
Note:
1: group 1 gels containing 1.50% (w/w) fumaric acid, 1.00% (w/w) propionic acid, 0.08% (w/w) cinnamic acid, 0.25% (w/w) phenethyl alcohol, 1.40% (w/w) maltose, 2.15% (w/w) xanthan gum, adjusted to pH 3.8
2: group 2 gels containing 1.50% (w/w) adipic acid, 1.00% (w/w) propionic acid, 0.08% (w/w) cinnamic acid, 0.25% (w/w) phenethyl alcohol, 1.40% (w/w) maltose, 2.15% (w/w) xanthan gum, adjusted to pH 3.8
3: note 4 of in vivo experiment I
The results show that:
1. as can be seen from table 34, group 1 experimental results: pH 3.8, gel containing "1.50% (w/w) fumaric acid, 1.00% (w/w) propionic acid, 0.08% (w/w) cinnamic acid, 0.25% (w/w) phenethyl alcohol, 1.40% (w/w) maltose, 2.15% (w/w) xanthan gum", administered 5 times, the pH of vaginal secretion of 2 cynomolgus monkeys remained 5.4, vaginal flora Nugent scored 1 still > 7 points, and another 1 dropped to 4-6 points
2. From the results of the experiment in group 2 of table 34, it can be seen that: a gel with a pH value of 3.8 and containing 1.50% (w/w) adipic acid, 1.00% (w/w) propionic acid, 0.08% (w/w) cinnamic acid, 0.25% (w/w) phenethyl alcohol, 1.40% (w/w) maltose and 2.15% (w/w) xanthan gum, the pH value of the vaginal secretion of 2 cynomolgus monkeys is reduced to 4.1 for 2 times, and the Nugent score of the vaginal flora is reduced to 0-3 points.
As can be seen from the above, the gel containing 1.50% (w/w) adipic acid in the experiment has the effects of inhibiting abnormal vaginal flora, recovering lactobacillus in vagina and recovering vaginal acidity.
Clinical observation one
10 patients with Bacterial Vaginosis (BV), 5 healthy volunteers, 1 time per day and 4.5g per time of gel A, continuous 5-day intravaginal administration, 3 days (V1) after administration and 3 days (V2) after cessation of administration, taking vaginal swabs to measure pH and smear staining microscopy, and observing the influence of the gel on the pH of vaginal secretions and vaginal flora, wherein the experimental results are shown in Table 35:
TABLE 35 Effect of gel A on vaginal acidity and flora in BV patients and healthy volunteers
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) phenethyl alcohol, 1.00% (w/w) citric acid, 1.60% (w/w) maltose, 0.20% (w/w) palatinose, 0.0005% (w/w) rose essential oil, 2.15% (w/w) xanthan gum, and is adjusted to pH 3.70
Note 2: the pH value is measured by using a colorimetric card with a pH standard range, the colorimetric card is divided into two ranges, 3.8-4.1 shows normal, 4.6-5.4 shows abnormal
Note 3: note 7 of in vivo experiment I
The results show that:
1. as can be seen from the BV patient test results in table 35: 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) phenethyl alcohol, 1.00% (w/w) citric acid, 1.60% (w/w) maltose, 0.20% (w/w) palatinose, 0.0005% (w/w) rose essential oil, 2.15% (w/w) xanthan gum" was administered 3 times, and 7 of 10 BV patients had their pH reduced to 3.8-4.1, 3 of vaginal flora Nugent scores reduced to 3 and below, and 4 to 4-6.
After 5 times of administration, the administration is stopped for 3 days for observation, and the pH value of 9 patients with 10 BV is reduced to 3.8-4.1, the pH value of vaginal flora Nugent is reduced to below 3 points, the pH value of 1 patient is still 4.6-5.4, and the pH value of vaginal flora Nugent is reduced to 6 points.
2. From the results of the experiments in healthy volunteers in table 35 it can be seen that: 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) phenethyl alcohol, 1.00% (w/w) citric acid, 1.60% (w/w) maltose, 0.20% (w/w) palatinose, 0.0005% (w/w) rose essential oil and 2.15% (w/w) xanthan gum has a pH value of 3.70, and has no influence on the pH value of vaginal secretion and vaginal flora of healthy volunteers after being applied for 3 times.
After 5 times of administration, the medicine is stopped for 3 days for observation, and the pH value and the flora of vaginal secretion of healthy volunteers are not affected.
In summary, it can be seen that: 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) phenethyl alcohol, 1.00% (w/w) citric acid, 1.60% (w/w) maltose, 0.20% (w/w) palatinose, 0.0005% (w/w) rose essential oil and 2.15% (w/w) xanthan gum' with the pH value of 3.70 in the experiment can obviously reduce abnormal flora, obviously increase lactobacillus and reduce the pH value in the vagina of BV patients, but has no influence on the pH value and normal flora of normal vaginal secretion of healthy volunteers, and the gel is prompted to have the effects of inhibiting abnormal vaginal flora, recovering and/or maintaining vaginal lactobacillus and recovering and/or maintaining normal vaginal acidity.
Reference documents:
1. fang Liang main braiding: pharmacy, national institutes of health, 2016, 8 th edition, pages 243-252;
2. fang Liang master code: pharmacy, national institutes of health, 2016, 8 th edition, pages 211-228;
3. fang Liang main braiding: pharmacy, national institutes of health, 2016, 8 th edition, pages 234-237;
4. fang Liang main braiding: pharmacy, min health Press, 2016, 8 th edition, pages 280-284.
While the present invention has been described with reference to exemplary embodiments, it is to be understood that the invention is not limited to the disclosed exemplary embodiments. Many modifications and variations may be made to the exemplary embodiments of the present description without departing from the scope or spirit of the present invention. The scope of the claims is to be accorded the broadest interpretation so as to encompass all modifications and equivalent structures and functions.
Claims (24)
- A bacteriostatic composition is characterized by comprising the following components:(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, caprylic acid, nonanoic acid, capric acid, undecanoic acid, undecylenic acid, and lauric acid, in a total content of component (1) in terms of fatty acids in the range of 0.001-3.00% (w/w);(2) One or more dibasic acids selected from the group consisting of glutaric acid, adipic acid, and pimelic acid, in a total content of component (2) in the range of 0.05-5.00% (w/w) based on dibasic acid, and/or salts thereof;(3) One or more aromatic alcohols selected from the group consisting of benzyl alcohol, 2,4-dichlorobenzyl alcohol, phenethyl alcohol, phenoxyethanol, and cinnamyl alcohol, the total content of component (3) being in the range of 0.03-1.00% (w/w);(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, the total content of component (4) being in the range of 0.03-1.00% (w/w) based on aromatic acids;the formulation of the antibacterial composition is one selected from the group consisting of an aqueous solution, a water-soluble gel, a foam, a spray, an ointment, a powder, a membrane, a capsule, a suppository and a tablet.
- Bacteriostatic composition according to claim 1, wherein the total content of component (1) in the bacteriostatic composition is in the range of 0.001-2.00% (w/w); and/orThe total content of the component (2) is in the range of 0.10-3.50% (w/w); and/orThe total content of the component (3) is in the range of 0.03-0.70% (w/w); and/orThe total content of component (4) is in the range of 0.03-0.50% (w/w).
- Bacteriostatic composition according to claim 1, further comprising component (5): one or more dibasic and/or polybasic acids selected from the group consisting of malic, citric, succinic, tartaric, maleic, and isocitric acid, and/or salts thereof, in a total amount ranging from 0.10 to 2.50% (w/w).
- Bacteriostatic composition according to claim 1, further comprising one or more sugars selected from the group consisting of glucose, fructose, mannose, galactose, maltose, isomaltose, sucrose, isomaltulose, lactose, lactulose, trehalose, cellobiose, melibiose, gentiobiose, kestose, nystose, kestose, isomaltotriose, gentiooligosaccharide, raffinose, panose, maltooligosaccharides, isomaltooligosaccharides, fructooligosaccharides, glucomannas, galactooligosaccharides, dextrins, starches, and glycogen, in a total content in the range of 0.01-20.00% (w/w), preferably in a total content in the range of 0.10-2.00% (w/w).
- Bacteriostatic composition according to 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 in a total amount in the range of 0.10-6.00% (w/w), preferably in a total amount in the range of 0.50-3.00% (w/w).
- Bacteriostatic composition according to claim 1, wherein the bacteriostatic composition further comprises one or more monoterpene or sesquiterpene compounds selected from the group consisting of citronellol, linalool, geraniol, nerol, eucalyptol, terpineol, carveol, menthol and lavandulol.
- Bacteriostatic composition according to claim 1, wherein the bacteriostatic composition further comprises one or more plant aromatic oils selected from the group consisting of rose essential oil, clove oil, thyme oil, lavender oil, peppermint oil, mugwort oil, eucalyptus oil, sassafras oil, litsea cubeba essential oil, cinnamon essential oil, bay leaf oil, and thyme oil.
- Bacteriostatic composition according to claim 1, wherein said bacteriostatic composition further comprises one or more vitamins selected from the group consisting of vitamin A, vitamin C, vitamin D, and vitamin E.
- Bacteriostatic composition according to 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, bergenin, tropolone, cinnamaldehyde, pseudolaric acid, chlorogenic acid, 1,2-pentanediol, 1,2-hexanediol, 1,6-hexanediol, 1,2-octanediol, 1,2-decanediol, p-hydroxyacetophenone, 2,4-dihydroxyacetophenone, methyl p-hydroxybenzoate, ethyl p-hydroxybenzoate, propyl p-hydroxybenzoate, lysozyme, glyceryl monocaprylate, glyceryl monocaprate, and glyceryl monolaurate.
- Bacteriostatic composition according to claim 1, wherein the bacteriostatic composition further comprises one or more antibacterial agents selected from the group consisting of nitroimidazoles, such as metronidazole, tinidazole, ornidazole; aminoglycoside drugs such as gentamicin, tobramycin, amikacin, sisomicin, netilmicin; quinolones, such as ciprofloxacin, ofloxacin, levofloxacin; furans, such as nifuratel, nifuratel oxime, nitrofurazone, furazolidone, nitrofurantoin; sulfonamides, such as silver sulfadiazine, sodium sulfacetamide; azoles, such as clotrimazole, fluconazole, miconazole, ketoconazole; allylamines, such as naftifine, terbinafine; polyene antibiotics, such as amphotericin B, nystatin, zymostatin, and natamycin.
- Bacteriostatic composition according to claim 1, wherein the bacteriostatic composition is an aqueous solution, a water-soluble gel, a foam, a spray, and an ointment having a pH value in the range of 3.1-4.8, preferably in the range of 3.6-4.6, more preferably in the range of 3.8-4.4.
- Bacteriostatic composition according to 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 the form of one of the following groups: pharmaceuticals, disinfectants, antimicrobials, bacteriostats, skin mucosal surface microbicides, flora modulators, microecologics, microenvironment modulators, microbiology modulators, disposable medical supplies or in the form of components of medical devices, pharmaceutical devices, disinfection devices and vaginal devices.
- Bacteriostatic composition according to 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 present in the form of one of the following groups: health products, hygiene products, personal care products, cosmetics, disposable hygiene products, cleaning products, household products, micro-ecological care products, deodorants, lubricants, moisturizers, lotions, cleansers, maintenance agents, antipruritics, fresheners, or in the form of sanitary napkins, panty liners, and tampons.
- The bacteriostatic composition according to claim 1, wherein the bacteriostatic composition is a bacteriostatic composition for vagina, and the bacteriostatic composition for vagina comprises the following components:(1) One or more fatty acids selected from the group consisting of acetic acid, glycolic acid, lactic acid, propionic acid, levulinic acid, butyric acid, valeric acid, caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, undecanoic acid, undecylenic acid, and lauric acid, wherein the total content of component (1) in terms of fatty acids is in the range of 0.001-2.00% (w/w);(2) One or more dibasic acids and/or salts thereof, selected from the group consisting of glutaric acid, adipic acid, and pimelic acid, the total content of component (2) based on dibasic acids being in the range of 0.50-2.50% (w/w);(3) One or more aromatic alcohols selected from the group consisting of benzyl alcohol, 2,4-dichlorobenzyl alcohol, phenethyl alcohol, phenoxyethanol, and cinnamyl alcohol, component (3) having a total content in the range of 0.05-0.60% (w/w);(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, the total content of component (4) based on aromatic acids being in the range of 0.05-0.25% (w/w).The formulation of the bacteriostatic composition for vagina 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.
- A method of inhibiting harmful microorganisms comprising the step of using the bacteriostatic composition according to any one of claims 1 to 14.
- The method of claim 15, wherein said detrimental microorganisms comprise: candida, staphylococcus aureus, escherichia coli, pseudomonas aeruginosa, gardnerella vaginalis, prevotella, campylobacter, aspergillus niger, and abnormal flora of human skin and/or mucosal sites.
- A method of modulating vaginal flora comprising the step of using a vaginal bacteriostatic composition comprising one or more fatty acids and/or salts thereof selected from the group consisting of butyric acid, valeric acid, caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, undecanoic acid, undecylenic acid, and lauric acid, wherein the total content of said fatty acids and/or salts thereof, calculated as fatty acids, is in the range of 0.001-2.00% (w/w);wherein the formulation of the bacteriostatic composition for vagina is selected from the group consisting of aqueous solution, water-soluble gel, foam, spray, ointment, powder, membrane, capsule, suppository and tablet;the modulation of vaginal flora comprises at least one of the following: inhibiting vaginal abnormal flora, restoring and/or maintaining vaginal lactobacilli.
- The method according to claim 17, wherein the bacteriostatic vaginal composition further comprises one or more dibasic acids and/or salts thereof selected from the group consisting of glutaric acid, adipic acid, and pimelic acid, in a total amount ranging from 0.50 to 2.50% (w/w) based on dibasic acid.
- The method of claim 17, wherein the bacteriostatic vaginal composition further comprises 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 amount ranging from 0.05-0.60% (w/w).
- The method of claim 17, wherein the vaginal bacteriostatic composition 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, wherein the total content of the aromatic acids and/or salts thereof is in the range of 0.05-0.25% (w/w) based on aromatic acids.
- The method of claim 17, wherein the bacteriostatic vaginal composition further comprises one or more estrogens or phytoestrogens selected from the group consisting of diethylstilbestrol, hexestrol, estradiol, estrone, estriol, nilestriol, ethinylestradiol cyclopentyl ether, ethinylestradiol, protamestrolene, daidzin, daidzein, glycitein, puerarin, coumestrol, equol, apine, genistin, genistein, biochanin, coumestrol, formononetin, resveratrol, secoisolariciresinol, and lignans in a total amount ranging from 0.001 to 1.00% (w/w).
- The method according to claim 17, wherein the bacteriostatic vaginal composition is used for restoring and/or maintaining normal vaginal flora and/or restoring and/or maintaining normal vaginal microecology and/or restoring and/or maintaining normal vaginal acidity and/or cleaning and caring vagina and/or vulva and/or reducing and/or eliminating vaginal vulvar pruritus and/or pain and/or dryness and/or irritation and/or dyspareunia and/or reducing and/or eliminating abnormal leucorrhea and/or abnormal leucorrhea.
- The method according to claim 17, wherein the bacteriostatic vaginal composition is used for the prevention and/or treatment of vaginal dysbacteriosis, and/or bacterial vaginosis, and/or aerobic vaginosis, and/or cytolytic vaginosis, and/or vaginal candidiasis, and/or atrophic vaginitis.
- Use of a fatty acid and/or a salt thereof for the preparation of a bacteriostatic composition for modulating vaginal flora, characterized in that the fatty acid is selected from at least one of the group consisting of butyric acid, valeric acid, caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, undecanoic acid, undecylenic acid, and lauric acid, the total content of the fatty acid and/or salt thereof in the bacteriostatic composition, calculated as fatty acid, being in the range of 0.001-2.00% (w/w), the modulating vaginal flora comprising at least one of the following: inhibiting vaginal abnormal flora, restoring and/or maintaining vaginal lactobacilli.
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CN102470117A (en) * | 2009-10-08 | 2012-05-23 | 曾忠铭 | Composition comprising benzoic acid in combination with organic acid preservatives as active components and use thereof |
WO2018064978A1 (en) * | 2016-10-09 | 2018-04-12 | 曾忠铭 | Uses of bacteriostatic agent formula in preparing composition for vaginal use and composition for vaginal use |
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