Skin microbiome balance improving agent

Abstract

To provide skin flora balance improvers that selectively grow Staphylococcus epidermidis and selectively reduce Staphylococcus aureus.SOLUTION: A skin flora balance improver is prepared, which contains: one or more or two or more oily ingredients selected from the group consisting of soybean oil, almond oil, and cholesterol; and / or one or more or two or more selected from the group consisting of soy lecithin, ceramide or analogues thereof, urea, pyrrolidone carboxylic acid and salts thereof, casein and salts thereof, and cyclodextrin.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to an agent for improving the skin microbiota balance.

Background Art

[0002] Many bacteria (resident skin bacteria) inhabit the epidermis of human skin, and due to the action of these bacteria, it is possible to prevent damage by ultraviolet rays and reactive oxygen species, the invasion of viruses into the body, skin dryness, etc. Staphylococcus epidermidis is cited as a representative bacterium having the function of protecting the epidermis, and it is actually known that Staphylococcus epidermidis is less in sensitive skin compared to healthy skin.

[0003] Although the optimal pH of the skin is weakly acidic, when this balance is disrupted and it tends to become alkaline, it is said that Staphylococcus aureus which is a kind of bad bacteria proliferates. As a result, the barrier function decreases and it becomes easier to be affected by external adverse effects, and it is known that skin troubles such as acne occur and atopic skin diseases are worsened.

[0004] The balance of the inhabitation of such various bacteria that normally inhabit the human skin in the epidermis maintains the skin barrier function, but when the inhabitation balance is disrupted, it develops into skin troubles. Skin troubles include, in addition to dryness and inflammation, infectious diseases. For example, suppurative skin diseases such as folliculitis, boils, and carbuncles are also known as one of them. In addition, it has also been reported that an abnormal composition of microbial species called Dysbiosis is observed in many skin diseases such as vitiligo and psoriasis, and it is considered that the balance of skin resident bacteria is deeply involved in the disease state in all cases.

[0005] It has been proposed to adjust the balance of resident skin bacteria by a specific plant extract (Patent Document 1).

Prior Art Documents

Patent Documents

[0006] [Patent Document 1] Japanese Patent Publication No. 2007-153800 [Overview of the project] [Problems that the invention aims to solve]

[0007] Currently, there are not many reported formulations that directly have an effect on restoring this balance of skin microbiota.

[0008] The present invention has been made in view of the above, and aims to provide an agent for improving the balance of habitation on the surface of fungi. [Means for solving the problem]

[0009] In view of the above-mentioned problems, the present inventors conducted diligent studies and found that the balance of the skin microbiota can be restored by using one or more selected ingredients from the group consisting of a specific type of oily component, soy lecithin, ceramide or its analogues, urea, pyrrolidone carboxylic acid and its salts, casein and its salts, and cyclodextrin, thus completing the present invention.

[0010] In other words, the present invention provides the following skin microbiota balance improving agent, Staphylococcus epidermidis growth agent, or Staphylococcus aureus antibacterial agent. Section 1. One or more oily components selected from the group consisting of soybean oil, almond oil, and cholesterol; and / or One or more substances selected from the group consisting of soy lecithin, ceramide or its analogues, urea, pyrrolidone carboxylic acid and its salts, casein and its salts, and cyclodextrin; A skin microbiome balance improving agent containing [specific ingredient]. Section 2. One or more oily components selected from the group consisting of soybean oil, almond oil, and cholesterol; and / or One or more substances selected from the group consisting of soy lecithin, ceramide or its analogues, urea, pyrrolidone carboxylic acid and its salts, casein and its salts, and cyclodextrin; A Staphylococcus epidermidis growth agent containing the above-mentioned ingredients. Section 3. One or more oily components selected from the group consisting of soybean oil, almond oil, and cholesterol; and / or One or more substances selected from the group consisting of soy lecithin, ceramide or its analogues, urea, pyrrolidone carboxylic acid and its salts, casein and its salts, and cyclodextrin; An antibacterial agent for Staphylococcus aureus containing [specific ingredient].

[0011] Furthermore, the present invention relates to one or more oily components selected from the group consisting of soybean oil, almond oil, and cholesterol; and / or One or more substances selected from the group consisting of soy lecithin, ceramide or its analogues, urea, pyrrolidone carboxylic acid and its salts, casein and its salts, and cyclodextrin; This invention relates to a topical skin composition for improving the balance of skin microbiota, a topical skin composition for promoting the growth of Staphylococcus epidermidis, or a topical skin composition for antibacterial action against Staphylococcus aureus, which contains [the specified ingredient]. [Effects of the Invention]

[0012] The present invention's skin microbiome balance improving agent can restore the balance of resident skin bacteria, leading to healthier skin. [Modes for carrying out the invention]

[0013] [Skin microbiome balance improving agent] The present invention's skin microbiome balance improving agent is One or more oily components selected from the group consisting of soybean oil, almond oil, and cholesterol; and / or One or more substances selected from the group consisting of soy lecithin, ceramide or its analogues, urea, pyrrolidone carboxylic acid and its salts, casein and its salts, and cyclodextrin; It contains.

[0014] Here, the "bacteria" in the skin flora balance improver of the present invention refers to bacteria that normally inhabit the skin, mainly including Staphylococcus epidermidis and Staphylococcus aureus. "Balance improvement" specifically means growing bacteria that have a favorable effect on the skin, such as Staphylococcus epidermidis, reducing pathogenic bacteria such as Staphylococcus aureus, and making the skin condition good or maintaining it in a good condition.

[0015] Therefore, the skin flora balance improver of the present invention includes a Staphylococcus epidermidis growth agent and / or a Staphylococcus aureus antibacterial agent. Here, "antibacterial" means inhibiting the generation, growth, and proliferation of bacteria.

[0016] (Oil component) The skin flora balance improver of the present invention contains one or more oil components selected from the group consisting of soybean oil, almond oil, and cholesterol. One or more oil components selected from the group consisting of soybean oil, almond oil, and cholesterol may be commercially available and are not particularly limited.

[0017] When the skin flora balance improver, Staphylococcus epidermidis growth agent, or Staphylococcus aureus antibacterial agent of the present invention is contained in a topical skin composition or is in the form of a topical skin composition, the content of one or more oil components selected from the group consisting of soybean oil, almond oil, and cholesterol is, based on the total amount of the topical skin composition, from the viewpoint of more significantly exhibiting the effects of the present invention, preferably 0.00001% by mass to 55% by mass, more preferably 0.01% by mass to 3% by mass, and still more preferably 0.1% by mass to 1% by mass.

[0018] The soybean oil in the present invention is not limited, but commercially available ones may also be used. Examples of commercially available soybean oils include "Soybean Oil YM" (Nisshin Oillio Group, Ltd.), "Soybean White Press Oil" (Summit Oil Co., Ltd.), "SR Soybean" (Kroda Japan Co., Ltd.), "Soybean Oil" (Kaneda Co., Ltd.), and the like.

[0019] When the skin microbiota balance improver, Staphylococcus epidermidis growth promoter, or Staphylococcus aureus antibacterial agent of the present invention is contained in a topical skin composition or is in the form of a topical skin composition, from the viewpoint of exerting the effects of the present invention, the content of soybean oil is preferably 0.00001% by mass to 40% by mass, more preferably 0.01% by mass to 1% by mass, and still more preferably 0.1% by mass to 1% by mass with respect to the total amount of the composition.

[0020] The almond oil in the present invention is not limited, and commercially available almond oil may be used. Examples of commercially available almond oil include "NIKKOL Sweet Almond Oil" (Nikao Chemicals Co., Ltd.), "Almond Oil" (Summit Oil Co., Ltd.), "Almond Oil" (GP TEXTRON Co., Ltd.), "CROPURE ALMOND" (Croda Japan Co., Ltd.), "SWEET ALMOND OIL" (GP TEXTRON Co., Ltd.), and the like.

[0021] When the skin microbiota balance improver, Staphylococcus epidermidis growth promoter, or Staphylococcus aureus antibacterial agent of the present invention is contained in a topical skin composition or is in the form of a topical skin composition, from the viewpoint of exerting the effects of the present invention, the content of almond oil is preferably 0.00001% by mass to 53% by mass, more preferably 0.001% by mass to 1% by mass, and still more preferably 0.01% by mass to 0.1% by mass with respect to the total amount of the composition.

[0022] When the skin microbiota balance improver, Staphylococcus epidermidis growth promoter, or Staphylococcus aureus antibacterial agent of the present invention is contained in a topical skin composition or is in the form of a topical skin composition, from the viewpoint of exerting the effects of the present invention, the content of cholesterol is preferably 0.005% by mass to 5% by mass, more preferably 0.01% by mass to 1% by mass, and still more preferably 0.05% by mass to​​​(Soy lecithin, ceramide or its analogues, urea, pyrrolidone carboxylic acid and its salts, casein and its salts, or cyclodextrin) In this invention, the soy lecithin used is preferably that which is listed in official standards such as the Japanese Pharmaceutical Additives Standards (Yakuji Nippo Co., Ltd.).

[0024] In the present invention, ceramide or its analogues are those in which a fatty acid is acid-amide bonded to the amino group of a sphingoid base. Examples include sphingophospholipids such as sphingomyelin and sphingosylphosphorylcholine, α-galactosylceramide, and sphingoglycolipids such as cerebroside and ganglioside.

[0025] The ceramide analog may be a pseudo-ceramide that has a chemical structure and properties similar to natural ceramide, and examples include N-(2-hydroxy-3-hexadecyloxypropyl)-N-2-hydroxyethylhexadecanamide, trihydroxypalmitamide hydroxypropyl myristyl ether, and cetylhydroxyproline palmitamide.

[0026] The cyclodextrin in this invention is a type of cyclic oligosaccharide having a structure in which glucose molecules are linked cyclically by α-1,4 bonds. Cyclodextrins are called α-type (α-cyclodextrin, 6 glucose molecules), β-type (β-cyclodextrin, 7 glucose molecules), γ-type (γ-cyclodextrin, 8 glucose molecules), etc., depending on the number of glucose molecules they contain. It is known that cyclodextrins composed of even more glucose molecules also exist in nature. The cyclodextrin compound used in this invention may be cyclodextrin or a salt thereof, and any pharmaceutically or physiologically acceptable salt can be used.

[0027] In this specification, "salt" is not limited to, but examples include salts with alkali metals, alkaline earth metals, organic bases, etc., and salts with sodium, potassium, calcium, magnesium, ammonium, or diethanolamine, ethylenediamine, etc. Furthermore, examples include salts of amines such as ammonia, methylamine, dimethylamine, trimethylamine, dicyclohexylamine, tris(hydroxymethyl)aminomethane, N,N-bis(hydroxyethyl)piperazine, 2-amino-2-methyl-1-propanol, ethanolamine, N-methylglucamine, L-glucamine, etc., or salts with basic amino acids such as lysine, δ-hydroxylysine, arginine, etc.

[0028] In the present invention, the salts of pyrrolidone carboxylic acid and casein are not limited, but preferably include sodium pyrrolidone carboxylic acid, zinc pyrrolidone carboxylic acid, and sodium caseinate. In the present invention, the pyrrolidone carboxylic acid and its salts are particularly preferably "dl-sodium pyrrolidone carboxylic acid solution" as described in the Pharmaceutical Additives Standards (Yakuji Nippo Co., Ltd.).

[0029] When the skin microbiome balance improving agent, Staphylococcus epidermidis growth agent, or Staphylococcus aureus antibacterial agent of the present invention is included in a topical skin composition or is in the form of a topical skin composition, the soy lecithin content is preferably 0.05% to 16% by mass, more preferably 0.1% to 2% by mass, and even more preferably 0.1% to 0.8% by mass, relative to the total amount of the composition, from the viewpoint of exhibiting the effects of the present invention.

[0030] When the skin microbiome balance improving agent, Staphylococcus epidermidis growth agent, or Staphylococcus aureus antibacterial agent of the present invention is included in a topical skin composition or is in the form of a topical skin composition, the content of ceramide or its analogue is preferably 0.01% to 5% by mass, more preferably 0.05% to 1% by mass, and even more preferably 0.1% to 0.5% by mass, based on the total amount of the composition, from the viewpoint of exhibiting the effects of the present invention.

[0031] When the skin microbiome balance improving agent, Staphylococcus epidermidis growth agent, or Staphylococcus aureus antibacterial agent of the present invention is included in a topical skin composition or is in the form of a topical skin composition, the urea content is preferably 0.005% to 20% by mass, more preferably 0.05% to 10% by mass, and even more preferably 0.1% to 5% by mass, based on the total amount of the composition, from the viewpoint of exhibiting the effects of the present invention.

[0032] When the skin microbiome balance improving agent, Staphylococcus epidermidis growth agent, or Staphylococcus aureus antibacterial agent of the present invention is included in a topical skin composition or is in the form of a topical skin composition, the content of pyrrolidone carboxylic acid and its salt is preferably 0.0005% to 5% by mass, more preferably 0.005% to 1% by mass, and even more preferably 0.05% to 0.1% by mass, based on the total amount of the composition, from the viewpoint of exhibiting the effects of the present invention.

[0033] When the skin microbiome balance improving agent, Staphylococcus epidermidis growth agent, or Staphylococcus aureus antibacterial agent of the present invention is included in a topical skin composition or is in the form of a topical skin composition, the content of casein and its salt is preferably 0.001% to 5% by mass, more preferably 0.01% to 1% by mass, and even more preferably 0.05% to 0.3% by mass, relative to the total amount of the composition, from the viewpoint of exhibiting the effects of the present invention.

[0034] When the skin microbiome balance improving agent, Staphylococcus epidermidis growth agent, or Staphylococcus aureus antibacterial agent of the present invention is included in a topical skin composition or is in the form of a topical skin composition, the cyclodextrin content is preferably 0.001% to 5% by mass, more preferably 0.01% to 1% by mass, and even more preferably 0.05% to 0.3% by mass, relative to the total amount of the composition, from the viewpoint of exhibiting the effects of the present invention.

[0035] [Optional ingredients] The skin microbiome balance improving agent, Staphylococcus epidermidis growth agent, Staphylococcus aureus antibacterial agent, or topical skin composition of the present invention may contain optional components as long as they do not impair the effects of the present invention. Examples of optional components include soybean oil, almond oil, oils other than cholesterol, thickeners, anti-inflammatory components, antioxidants, cooling agents, antibacterial / bactericidal agents, vitamins, organic acids, moisturizing components, alcohols, amino acids or their derivatives, surfactants, colorants, pH adjusters, chelating agents, etc. In the present invention, each of these components may be blended individually or in combination of two or more.

[0036] Examples of the above-mentioned lubricants include polar oils and non-polar oils. Examples of polar oils include ester oils and waxes, but are not limited to these. Ester oils and waxes are preferred as polar oils, with ester oils being more preferred. Examples of non-polar oils include hydrocarbon oils and silicone oils, but are not limited to these.

[0037] Examples of hydrocarbon oils include petrolatum, squalane, squalene, liquid paraffin, paraffin, pristane, and polyisobutylene. Of these, petrolatum, liquid paraffin, paraffin, and squalane are preferred.

[0038] Examples of ester oils include isopropyl myristate, butyl myristate, decyl myristate, myristyl myristate, cetyl myristate, isopropyl palmitate, cetyl palmitate, ethyl stearate, butyl stearate, stearyl stearate, isocetyl stearate, hexyl laurate, ethyl oleate, ethyl linoleate, isopropyl linoleate, cetyl caprylate, decyl oleate, oleyl oleate, isodecyl oleate, cetyl octanoate, 2-octyldodecyl myristate, and dimethylocta. 2-Octyldodecyl Sebacate, Hexyldecyl Dimethyloctanoate, Diethyl Sebacate, Diisopropyl Sebacate, Di-2-Ethylhexyl Sebacate, 2-Hexyldecyl Myristate, 2-Hexyldecyl Palmitate, Diisopropyl Adipate, 2-Hexyldecyl Adipate, Isocetyl Isostearate, Isostearyl Isostearate, Isononyl Isononanoate, Isotridecyl Isononanoate, Cholesteryl 12-Hydroxystearylate, Cholesteryl Stearate, Cholesteryl Oleate, Macadamia Nut Fatty Acid Phytosteryl Phytosteryl oleate, inulin stearate, ethylene glycol di-2-ethylhexylate, cetyl 2-ethylhexanoate, N-alkyl glycol monoisostearate, neopentyl glycol dicaprate, glycerin di-2-heptylundecanoate, tri-2-ethylhexyl trimellitate, tridecyl trimellitate, trimethylolpropane tri-2-ethylhexylate, trimethylolpropane triisostearate, pentaerythritol tetra-2-ethylhexanoate, glycerin tri-2-ethylhexanoate, triiso Trimethylolpropane stearate, cetyl 2-ethylhexanoate, glyceryl trimyristate, caprylic / capric triglyceride, medium-chain triglyceride, caprylic / capric / myristic / stearic triglyceride, castor oil fatty acid methyl ester, diisobutyl adipate, phytosteryl / octyldodecyl lauroyl glutamate, octyldodecyl / phytosteryl / behenyl lauroyl glutamate, di-2-heptylundecyl adipate, diisostearyl malate, cetyl lactate,Examples include myristyl lactate, diethoxyethyl succinate, diethylhexyl succinate, bisethoxydiglycol cyclohexane-1,4-dicarboxylic acid, lanolin acetate, ethyl acetate, butyl acetate, amyl acetate, triethyl citrate, dimer dilinoleyl (phytosteryl / isostearyl / cetyl / stearyl / behenyl) dimer dilinoleate, dipentaerythrityl tripolyhydroxystearate, and glyceryl tri(behenate / isostearate / eicosanedioate). Of these, isopropyl palmitate, 2-ethylhexyl palmitate, 2-hexyldecyl palmitate, 2-heptylundecyl palmitate, and diethyl sebacate are preferred, with isopropyl palmitate and diethyl sebacate being more preferred.

[0039] Examples of silicone oils include methylpolysiloxane, dimethylpolysiloxane, methylphenylpolysiloxane, decamethyltetrasiloxane, methylcyclopentasiloxane, highly polymerized methylpolysiloxane, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, methylhydrogenpolysiloxane, siloxanes such as methyltrimethicone, dimethiconol, and dimethiconol crosspolymer, alkyl-modified silicones such as caprylyl methicone, amino-modified silicones such as aminopropyl dimethicone and amodimethicone, cross-linked methylpolysiloxane, cross-linked alkyl-modified silicone, amino-modified silicone, polyether-modified silicone, polyglycerin-modified silicone, cross-linked polyether-modified silicone, cross-linked alkyl polyether-modified silicone, silicone-alkyl chain-comodified polyether-modified silicone, silicone-alkyl chain-comodified polyglycerin-modified silicone, polyether-modified branched silicone, polyglycerin-modified branched silicone, acrylic silicone, phenyl-modified silicone, and silicone resins. Of these, dimethylpolysiloxane is preferred.

[0040] Examples of waxes include candelilla wax, rice bran wax, cotton wax, carnauba wax, lanolin, isopropyl lanolin fatty acid, POE lanolin alcohol ether, POE lanolin alcohol acetate, polyethylene glycol lanolin fatty acid, POE hydrogenated lanolin alcohol ether, shellac wax, and beeswax.

[0041] Examples of the thickening agents mentioned above include hydroxypropyl methylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, carboxyethylcellulose, hydrophobized hydroxypropyl methylcellulose, guar gum, pectin, pullulan, gelatin, locust bean gum, carrageenan, agar, xanthan gum, gellan gum, polysaccharides such as alginic acid, propylene glycol alginate, sodium chondroitin sulfate, hyaluronic acid, and sodium hyaluronate, vinyl-based thickening agents such as polyvinyl alcohol, polyvinylpyrrolidone, and carboxyvinyl polymer, alkyl acrylate methacrylate copolymer, polyethylene glycol, bentonite, (hydroxyethyl acrylate / sodium acryloyldimethyltaurate) copolymer, and (ammonium acryloyldimethyltaurate / vinylpyrrolidone) copolymer.

[0042] Examples of the above anti-inflammatory components include allantoin and its derivatives, calamine, tranexamic acid, glycyrrhizic acid or its derivatives or salts thereof, glycyrrhetinic acid or its derivatives or salts thereof, zinc oxide, aminocaproic acid, azulene and its derivatives, tocopherol acetate, pyridoxine hydrochloride, menthol, camphor, turpentine oil, indomethacin, salicylic acid or its derivatives, steroids and their salts, ufenamate, bufexamac, ibuprofen piconol, calamine, azelaic acid, and components derived from plants (e.g., comfrey, coptis japonica, houttuynia cordata, chamomile, bilberry, rosehip, and sorrel).

[0043] Examples of the above-mentioned antioxidants and preservatives include butylhydroxyanisole, dibutylhydroxytoluene, sodium bisulfite, sodium pyrosulfite, sorbic acid and its salts, erythorbic acid and its salts, ascorbic acid and its salts, tocopherol and its derivatives, tocotrienol, L-cysteine ​​hydrochloride, ubiquinones such as coenzyme Q10, flavonoids, glutathione, glutathione peroxidase, glutathione-S-transferase, catalase, and superoxide dismutase. Examples include ze, thioredoxin, taurine, thiotaurine, hypotaurine, and components derived from plants (for example, St. John's wort, kudzu, bilberry, scutellaria, passion fruit, grapefruit, peony, meadowsweet, perilla, honeysuckle, sage, yarrow, mallow, meadowsweet, mulberry bark, clove, dried tangerine peel, geranium, loquat, safflower, peony peel, hops, eucalyptus, saxifrage, rooibos, lemongrass, mugwort, evening primrose, rosemary, lavender, etc.).

[0044] Examples of the cooling agents mentioned above include terpenes such as menthol, camphor, and geraniol (these may be d-isomers, l-isomers, or dl-isomers), and essential oils such as eucalyptus oil, bergamot oil, peppermint oil, cool mint oil, spearmint oil, and peppermint oil.

[0045] Examples of the above-mentioned antibacterial, disinfectant, and preservative agents include chlorhexidine, salicylic acid, benzalkonium chloride, acrinol, ethanol, benzethonium chloride, cetyltrimethylammonium chloride, cresol, gluconic acid and its derivatives, povidone-iodine, potassium iodide, iodine, isopropylmethylphenol, triclocarban, triclosan, zinc pyrithione, photosensitizer 101, photosensitizer 201, parabens, phenoxyethanol, alkyldiaminoglycine hydrochloride, cetylpyridinium chloride, piroctoolamine, miconazole or its salts, chlorobutanol, ethylhexylglycerin, iodidepropynyl butylcarbamate, caprylhydroxamic acid, phenethyl alcohol, methylisothiazolinone, sorbic acid, β-glycyrrhetinic acid, and components derived from azelaic acid.

[0046] The above vitamins may be either water-soluble or fat-soluble vitamins, for example, vitamin B6, pantothenic acid, nicotinic acid, vitamin B1, vitamin B2, biotin, folic acid, vitamin B 12 Examples include water-soluble vitamin C compounds, oil-soluble vitamin C compounds, tocopherol and its derivatives, vitamin K compounds, and vitamin-like factors such as ferulic acid.

[0047] Examples of the above organic acids include gluconic acid, aspartic acid, aminoethylsulfonic acid, citric acid, glutamic acid, oxalic acid, fumaric acid, propionic acid, malic acid, salicylic acid, glycolic acid, phytic acid, acetic acid, lactic acid, and salts thereof. Examples of salts include salts of mineral acids such as sulfuric acid, hydrochloric acid, or phosphoric acid, salts of organic acids such as maleic acid or methanesulfonic acid, alkali metal salts such as sodium or potassium, and alkaline earth metal salts.

[0048] Examples of the above moisturizing ingredients include hyaluronic acid or its salts or derivatives (e.g., sodium hyaluronate, zinc hyaluronate, low molecular weight hyaluronic acid, acetylated hyaluronic acid, cross-linked hyaluronic acid derivatives, cationized hyaluronic acid, etc.); chondroitin sulfate or its salts; heparin-like substances, amino acids such as alanine, serine, aspartic acid, glycine, arginine and their derivatives; polyhydric alcohols such as glycerin, dipropylene glycol, and 1,3-butanediol; sorbitol, xylitol, erythritol, maltose-sucrose condensate (gluco-oligosaccharide), hydrolyzed xylan ( Examples include sugar alcohols such as xylooligosaccharides; alkylene oxides such as PPG-17 buteth-17, PPG-25 sorbitol, polyoxyalkylene alkyl glucoside, PEG / PPG / polybutylene glycol-8 / 5 / 3 glycerin, and polyoxyalkylenediglyceryl; glycosyl trehalose, trehalose; phytosterols, cholesterol derivatives, phytosterol derivatives; MPC polymers; NMF-derived components such as lactic acid and sodium lactate; collagen, elastin, keratin, chitin, chitosan, etc. and their hydrolysates; and components derived from hydroxyethyl urea.

[0049] Examples of the alcohols mentioned above include lower alcohols such as ethanol and isopropyl alcohol, higher alcohols, and polyhydric alcohols. Examples of higher alcohols include linear alcohols (lauryl alcohol, cetyl alcohol, stearyl alcohol, arachidyl alcohol, behenyl alcohol, myristyl alcohol, oleyl alcohol, cetostearyl alcohol, etc.) and branched alcohols (monostearyl glyceryl ether ((batyl alcohol)), 2-decyltetradecacinol, hexyldodecanol, isostearyl alcohol, octyldodecanol, etc.). As polyhydric alcohols, those having 2 to 10 carbon atoms are preferred, and examples include glycerin, diglycerin, triglycerin, propylene glycol, dipropylene glycol, 1,3-butanediol, ethylene glycol, diethylene glycol, isoprene glycol, 1,3-butylene glycol, 1,3-propanediol, 1,2-pentanediol, 1,2-hexanediol, 1,2-octanediol, sorbitol, xylitol, erythritol, mannitol, decanediol, neopentyl glycol, and the like.

[0050] Examples of the above amino acids or their derivatives include betaine (trimethylglycine), proline, hydroxyproline, arginine, lysine, serine, glycine, alanine, phenylalanine, β-alanine, threonine, glutamic acid, glutamine, asparagine, aspartic acid, cysteine, cystine, methionine, leucine, isoleucine, valine, histidine, taurine, γ-aminobutyric acid, γ-amino-β-hydroxybutyric acid, carnitine, carnosine, creatine, and the like.

[0051] The above surfactants may be nonionic surfactants, cationic surfactants, anionic surfactants, amphoteric surfactants, etc., for example, sorbitan fatty acid esters such as sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan diglycerol penta-2-ethylhexyl sorbitan, sorbitan diglycerol tetra-2-ethylhexyl sorbitan; propylene glycol fatty acid esters such as propylene glycol monostearate; hydrogenated castor oil derivatives such as polyoxyethylene hydrogenated castor oil 40 (HCO-40), polyoxyethylene hydrogenated castor oil 50 (HCO-50), polyoxyethylene hydrogenated castor oil 60 (HCO-60), polyoxyethylene hydrogenated castor oil 80; polyoxyethylene monolauric acid Preferred surfactants include polyoxyethylene sorbitan fatty acid esters such as ethylene(20) sorbitan (polysorbate 20), polyoxyethylene(20) sorbitan monostearate (polysorbate 60), polyoxyethylene(20) sorbitan monooleate (polysorbate 80), and polyoxyethylene(20) sorbitan isostearate; polyoxyethylene monococonut oil fatty acid glyceryl; glycerin alkyl ethers; alkyl glucosides; polyoxyalkylene alkyl ethers such as polyoxyethylene cetyl ether; amines such as stearylamine and oleylamine; and silicone-based surfactants such as polyoxyethylene methylpolysiloxane copolymers, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, and PEG-9 polydimethylsiloxyethyl dimethicone.

[0052] Examples of the above-mentioned colorants include inorganic pigments and natural pigments.

[0053] Examples of the pH adjusting agents mentioned above include inorganic acids (hydrochloric acid, sulfuric acid, etc.), organic acids (lactic acid, sodium lactate, etc.), inorganic bases (potassium hydroxide, sodium hydroxide, etc.), and organic bases (triethanolamine, diisopropanolamine, triisopropanolamine, arginine, etc.).

[0054] Examples of the chelating agents mentioned above include ethylenediaminetetraacetic acid (EDTA), ethylenediaminetetraacetic acid salt (sodium salt (sodium edetate: Japanese Pharmacopoeia, EDTA-2Na, etc.), potassium salt, etc.), phytic acid, gluconic acid, polyphosphate, metaphosphate, etc.

[0055] (pH) When the skin microbiome balance improving agent, Staphylococcus epidermidis growth agent, or Staphylococcus aureus antibacterial agent of the present invention is included in a topical skin composition or is in the form of a topical skin composition, its pH is not limited as long as it is within a physiologically or pharmaceutically acceptable range, but for example, the pH can be 3 to 9, preferably 3.5 to 8.5, more preferably 4 to 8, and even more preferably 4.5 to 7.

[0056] (Dosage form) The skin microbiota balance improving agent, Staphylococcus epidermidis growth agent, or Staphylococcus aureus antibacterial agent of the present invention is preferably included in or in the form of an external composition, and is not particularly limited as long as it is a known form as a pharmaceutical, quasi-drug, or cosmetic. For example, it can be formulated by known methods in the form of a liquid, suspension, emulsion, cream, ointment, gel, liniment, lotion, aerosol, powder, or sheet impregnated with the components of the present invention. From the viewpoint of more significantly exhibiting the effects of the present invention, liquid, emulsion, or cream formulations are preferred as lotions, emulsions, or serums. By formulating in such forms, the effects can be fully exhibited. Thus, since the skin microbiota balance improving agent, Staphylococcus epidermidis growth agent, or Staphylococcus aureus antibacterial agent of the present invention can be applied in a so-called leave-on manner, unlike cleansing agents, it does not cause the loss of sebum or beneficial bacteria, and it is possible to balance the skin microbiota simply by applying it.

[0057] When formulated in liquid or semi-solid form, such as a liquid, suspension, emulsion, cream, ointment, gel, or lotion, the present invention's skin microbiota balance improving agent, Staphylococcus epidermidis growth agent, or Staphylococcus aureus antibacterial agent can be applied directly or indirectly to the desired affected area by housing it in a nozzle-equipped container, pump-equipped container, jar container, tube container, container with a hole in the inner stopper, hinge-capped container, sponge-head container, etc. The nozzle or sponge can also be designed to be tapered or have a large diameter to allow application to a narrow or wide area of ​​the affected area. After applying the present invention's skin microbiota balance improving agent, Staphylococcus epidermidis growth agent, or Staphylococcus aureus antibacterial agent to the affected area, it can also be spread using a non-woven fabric or fingers. In another embodiment, if the skin microbiome balance improving agent is formulated in liquid form such as a liquid, suspension, emulsion, cream, gel, or lotion, it can also be used by directly spraying the skin microbiome balance improving agent, Staphylococcus epidermidis growth agent, or Staphylococcus aureus antibacterial agent of the present invention onto the affected area by housing it in a spray container, although this is not limited to the present invention.

[0058] The application sites for the skin microbiota balance improving agent, Staphylococcus epidermidis growth agent, or Staphylococcus aureus antibacterial agent of the present invention are not particularly limited, but include the skin (including hair, nails, mucous membranes, etc.). Among these, the skin of the hands (palms, fingers), face, feet, head, neck, chest, armpits, and back is more preferred, with the palms, fingers, and skin being particularly preferred.

[0059] The appropriate settings may be determined depending on the use and formulation of the present invention's skin microbiome balance improving agent, Staphylococcus epidermidis growth agent, or Staphylococcus aureus antibacterial agent.

[0060] Since the skin microbiota influences barrier function, such as preventing the colonization of harmful microorganisms, applying the skin microbiota balance improving agent, Staphylococcus epidermidis growth agent, or Staphylococcus aureus antibacterial agent of the present invention to the skin is expected to maintain a healthy skin microbiota and contribute to the suppression of skin problems. Alternatively, it may be possible to achieve a skin condition that can be described as an increase in beneficial barrier bacteria. Furthermore, the skin microbiota balance improving agent, Staphylococcus epidermidis growth agent, or Staphylococcus aureus antibacterial agent of the present invention facilitates the secretion of fatty acids that maintain the skin's slightly acidic pH, thus making it easier to achieve beautiful skin. In addition, since Staphylococcus epidermidis secretes glycerin, a moisturizing component, it is expected that the skin will become moisturized, and the barrier function that protects the skin from dryness and external stimuli will be enhanced. Therefore, it may contribute to alleviating the symptoms of atopic dermatitis and sensitive skin, and to creating a skin condition that is less prone to infections.

[0061] (Manufacturing method) The skin microbiome balance improving agent, Staphylococcus epidermidis growth agent, or Staphylococcus aureus antibacterial agent of the present invention can be manufactured by known methods. Sterilization steps may be included as needed. [Examples]

[0062] Next, the present invention will be specifically described with reference to examples, but the present invention is not limited to the following examples.

[0063] [Test Example 1: Evaluation Test of Effects on Skin Resident Bacteria] The test substances listed in Table 3 were investigated to determine whether they affect the growth of Staphylococcus epidermidis and Staphylococcus aureus, which are commensal bacteria of the skin. The test substances listed in Table 3 were added to cultures of Staphylococcus epidermidis and Staphylococcus aureus, and DNA extraction was performed after 24 hours. The copy numbers of Staphylococcus epidermidis and Staphylococcus aureus were calculated using the quantitative PCR method determined in preliminary studies, and the increase or decrease in copy numbers after the addition of the test substances was confirmed.

[0064] The equipment used is as follows: Real-time PCR system: LightCycler 96 (Roche) High-speed refrigerated centrifuge: KUBOTA 7000 (manufactured by Kubota Shoji Co., Ltd.) Micro-volume spectrophotometer: DS-11 (manufactured by DeNovix) Spectrophotometer: Ultraspec2100 pro (Central Science Trading Co., Ltd.)

[0065] The reagents and test solutions used are shown in Table 1 below. [Table 1]

[0066] (Preliminary examination) 1. Examination of dissolution and suspension (1) Of the test substances in the examples, the water-soluble substance (urea) was dissolved in sterile water and sterilized by filtration using a 0.22 μm filter. (2) The solubility or suspension of each component was confirmed, and the concentration of the sample to be used in the test was determined. (3) Components that are difficult to dissolve or suspend, or components that increase viscosity when sterile water is added (i.e., sodium caseinate, β-cyclodextrin, soy lecithin, N-(2-hydroxy-3-hexadecyloxypropyl)-N-2-hydroxyethylhexadecanamide, dl-sodium pyrrolidone carboxylate solution, cholesterol) were suspended in the culture medium and sterilized by autoclaving (121°C for 20 minutes). (4) Lipid-soluble components (almond oil, soybean oil) were added directly to the culture medium to the final concentrations v / v% shown in Table 3.

[0067] 2. Culturing of Staphylococcus epidermidis and Staphylococcus aureus and confirmation of the effects of solvents. (1) A culture medium was prepared by adding 1.0 mL of ethanol (100% and 50%) or sterile water and citrate buffer to 8.9 mL of culture medium. This medium was dispensed into Falcon® round tubes in 990 μL portions. (2) Each prepared culture medium was divided into an ethanol group, a sterile water group, and a citrate buffer group, with 10 bottles prepared for each group. (3) Perform a culture test. 10 μL each of Staphylococcus epidermidis (EZ-shot bacterial suspension) and Staphylococcus aureus (preliminary culture medium) were added to two bottles of the respective prepared culture medium from 2) (initial culture). The bacteria were thoroughly dispersed using a vortex mixer, and 10 μL of each was taken from there and inoculated into 990 μL of the newly prepared culture medium from 2) (bacterial volume 1 / 100 dilution culture). This procedure was repeated once more (bacterial volume 1 / 10000 dilution culture), and the culture was incubated with shaking at 37°C for 18 to 24 hours. (4) The amount of bacteria required to achieve a turbidity of 2.0 or less was determined using a spectrophotometer.

[0068] 3. DNA extraction 200 μL of the bacterial culture medium prepared in step 2 above was added to a 1.5 mL tube, and 200 μL of 2×lysing solution (200 mM Tris-HCl (pH 8.0) / 60 mM EDTA / 1% SDS) was added. The mixture was then slowly pipetted and heated at 100°C for 15 minutes. Subsequently, 300 μL of phenol / chloroform / isoamyl alcohol (25:24:1) was added and mixed by vortex mixing. After centrifugation at 1200 rpm at room temperature for 10 minutes, 200 μL of the aqueous layer was transferred to a new 1.5 mL tube, and 6.6 μL of 3 M sodium acetate, 2 μL of ethanol precipitate mate, and 500 μL of ethanol were added and mixed by vortex mixing. The precipitate was dissolved in 20 μL of TE (10 mM Tris-HCl / 1 mM EDTA, pH 8.0), and the amount of DNA was measured using a micro spectrophotometer. The number of copies per DNA molecule was calculated from the amount of DNA and the total genome size.

[0069] 4. Real-time PCR (1) Calibration standards were prepared as shown in Table 2. [Table 2]

[0070] (2) A PCR mix was prepared in a 1.5 mL tube with the following composition and gently mixed. (Composition of PCR mix) 10 μM forward primer 0.4 μL 10 μM reverse primer 0.4 μL KAPA SYBR Fast qPCR Kit 10.0 μL Water (PCR grade) 6.2 μL 3.0 μL of each template DNA Total volume: 20.0 μL

[0071] Primer sequence Forward primer “Bac349F” 5'-AGGCAGCAGTDRGGAAT-3' Reverse primer “Bac806R” 5'-GGACTACYVGGGTATCTAAT-3'

[0072] (3) PCR was performed under the following conditions. Amplification at 95°C for 10 seconds, 65°C for 10 seconds, and 72°C for 1 second, repeated 45 times. (4) A calibration curve was created using the Ct values ​​of the standard DNA for the calibration curve, and this was used for the quantification in the following main test.

[0073] (This exam) Effects on DNA copy number of Staphylococcus epidermidis and Staphylococcus aureus (1) Add 1 mL of culture medium, diluted or suspended, of the test substance of the example or comparative example to a Falcon® round tube to the final concentration shown in Table 3. Inoculate 10 μL of Staphylococcus epidermidis and Staphylococcus aureus in the bacterial load determined in the preliminary test, and incubate with shaking at 37°C for 18 to 24 hours. (2) DNA was extracted using the same procedure as in (3) above, and real-time PCR was performed under the conditions set in (4). The DNA copy number of both Staphylococcus aureus strains was calculated from the obtained results. The ratio compared to the copy number without the test substance is shown below.

[0074] [Table 3]

[0075] As a result, it was found that almond oil, cholesterol, soybean oil, urea, sodium caseinate, ceramide analog, sodium pyrrolidone carboxylate, soy lecithin, and β-cyclodextrin have the effect of increasing Staphylococcus epidermidis and decreasing Staphylococcus aureus. These substances are thought to have the effect of improving the balance of the skin microbiota.

[0076] The following are examples of formulations for topical skin compositions used as skin microbiome balance improving agents according to the present invention. Note that all formulation examples in the table are cream formulations.

[0077] [Table 4]

[0078] [Table 5]

Claims

1. A skin microbiome balance improving agent containing only one or more active ingredients selected from the group consisting of almond oil, cholesterol, and pyrrolidone carboxylic acid or its salts.

2. A Staphylococcus epidermidis growth agent containing one or more selected from the group consisting of soybean oil, almond oil, cholesterol, soybean lecithin, N-(2-hydroxy-3-hexadecyloxypropyl)-N-2-hydroxyethylhexadecanamide, urea, pyrrolidone carboxylic acid or its salt, casein or its salt, and cyclodextrin.

3. An antibacterial agent for Staphylococcus aureus containing one or more selected from the group consisting of almond oil, casein or a salt thereof, and pyrrolidone carboxylic acid or a salt thereof.

4. A skin microbiome balance improving agent containing one or more selected from the group consisting of soybean oil, almond oil, cholesterol, soybean lecithin, N-(2-hydroxy-3-hexadecyloxypropyl)-N-2-hydroxyethylhexadecanamide, urea, pyrrolidone carboxylic acid or its salt, casein or its salt, and cyclodextrin, which promotes the growth of Staphylococcus epidermidis and suppresses the growth of Staphylococcus aureus.

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