Cell activator and composition for cell activation

Abstract

To provide a novel cell activator and a composition for cell activation.SOLUTION: A cell activator containing naringenin. Also, a composition for cell activation containing naringenin.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a cell activator and a composition for cell activating activity. [Background technology]

[0002] Flavonoids, a type of polyphenol found in plants, share a common structure of two benzene rings connected by three carbons and one oxygen atom, and thousands of variations are thought to exist in nature due to various modifications and sugar additions to this common structure. Some flavonoids are used as natural pigments, but there are also compounds that are believed to have beneficial effects on maintaining and promoting health through antioxidant and hormone-like effects, and these compounds are being investigated for application in foods, cosmetics, and pharmaceuticals.

[0003] Naringenin (4',5,7-trihydroxyflavanone) is a C 15 H 12 Naringenin is a flavonoid with a relatively simple structure of O5. Previous reports have shown that naringenin has antioxidant and anti-inflammatory properties. For example, Patent Document 1 discloses an invention that uses naringenin non-therapeutically in cosmetics or dermatology for the purposes of skin whitening, promoting skin tone uniformity, reducing pigmentation and darkening, and improving skin brightness. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] European Patent No. 2862600 Summary of the Invention [Problem to be solved by the invention]

[0005] In recent years, cosmetics have been required to have various functions to lead to beautiful skin. From the viewpoint of anti-aging, etc., there is a high demand for compounds having cell-activating effects.

[0006] Therefore, an object of the present invention is to provide a novel cell activator and a novel composition for cell activating activity. [Means for solving the problem]

[0007] The present invention includes the following aspects. (1) A cell activator containing naringenin. (2) The cell activator according to (1), which enhances the expression of at least one gene selected from the group consisting of KRT14, PCNA, EGFR, GRHL3, and HBEGF. (3) A cell-stimulating composition containing naringenin and a pharmaceutically acceptable carrier. (4) The cell-stimulating composition according to (3), which is a cosmetic. [Effects of the Invention]

[0008] According to the present invention, a novel cell activator and a novel cell activating composition are provided. [Brief explanation of the drawings]

[0009] [Figure 1] 1 shows the results of a cell activation test in Experimental Example 1. DETAILED DESCRIPTION OF THE INVENTION

[0010] Gene names in this specification are represented by the human gene symbols (official symbols of the Human Genome Nomenclature Committee (HGNC)) used in the NCBI nucleotide sequence database (GenBank®). When a specific gene name is represented by a human gene symbol, in animals other than humans, it refers to the ortholog of the gene for each animal (for example, one identified in the above-mentioned Gene database, etc.).

[0011] [Cell activators] A first aspect of the present invention is a cell activator containing naringenin, which contains naringenin as an active ingredient.

[0012] <Naringenin> Naringenin refers to 4',5,7-trihydroxyflavanone (also known as (2S)-2,3-dihydro-5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one). Naringenin is a compound represented by the following chemical formula:

[0013] [ka]

[0014] The method for producing naringenin is not particularly limited, and naringenin can be produced by known methods. The method for producing naringenin is not particularly limited, and known methods can be used. Naringenin may be a naturally occurring compound, a compound chemically synthesized using natural or artificial raw materials, or a compound obtained by precision fermentation using microorganisms, etc. Naturally occurring naringenin includes naringenin extracted and purified from plants such as citrus fruits (e.g., grapefruit, orange, etc.). Naringenin obtained by precision fermentation includes naringenin extracted and purified from a naringenin-producing microorganism (e.g., genetically modified Escherichia coli, etc.) cultured in the presence of an organic carbon source (e.g., glycerol, sugar, organic acid, amino acid, or biomass containing these, etc.).

[0015] <Application> A cell activator is a preparation that has a cell activating effect. "Cell activation" means enhancing the proliferation of normal cells. "Cell activating effect" means promoting the proliferation of normal cells. Cells that are the target of cell activation are not particularly limited, but examples thereof include skin cells. Skin cells may be cells present in the epidermis layer or cells present in the dermis layer. Examples of cells present in the epidermis layer include granular cells, spinous cells, Langerhans cells, basal cells, etc. Examples of cells present in the dermis layer include fibroblasts. It is believed that activating cells in the epidermal layer promotes normal epidermal turnover and maintains skin homeostasis, which is expected to improve skin problems (decreased barrier function, dry skin, itchiness, dullness, pigmentation, and pimples). It is believed that activating cells in the dermis layer promotes the production of collagen, hyaluronic acid, etc., and is therefore expected to have an anti-aging effect.

[0016] The cell activator of this embodiment may be used to enhance the expression of at least one gene selected from the group consisting of KRT14, PCNA, EGFR, GRHL3, and HBEGF. Enhancement of the expression of these genes in normal cells can produce a cell inactivating effect.

[0017] The "KRT14 gene" is a gene that encodes KRT14 (keratin 14). Keratin 14 is present in the basal layer of the epidermis and is involved in the normal division and proliferation of basal cells. Increased expression of the KRT14 gene is thought to promote the division and proliferation of basal cells in the epidermis, which is thought to strengthen the basement membrane. An example of the nucleotide sequence of the human KRT14 gene is the nucleotide sequence registered in the GenBank database under accession number NM_000526. The nucleotide sequence of the KRT14 gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as KRT14. The KRT14 gene encompasses homologs, paralogs, and orthologs of the KRT14 gene, as long as they encode a protein that functions as KRT14.

[0018] The "PCNA gene" is a gene that encodes PCNA (epidermal growth factor receptor; proliferating cell nuclear antigen). PCNA is a cofactor for DNA polymerase δ and is involved in DNA replication and repair, as well as cell cycle regulation. Increased expression of the PCNA gene is thought to promote epidermal turnover. An example of the nucleotide sequence of the human PCNA gene is the nucleotide sequence registered in the GenBank database under accession number NM_182649. The nucleotide sequence of the PCNA gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as PCNA. The PCNA gene encompasses homologs, paralogs, and orthologs of the human PCNA gene, as long as they encode a protein that functions as PCNA.

[0019] The "EGFR gene" is a gene that encodes EGFR (epidermal growth factor receptor). EGFR is a cell surface protein that induces cell proliferation by signal transduction through binding to epidermal growth factor. In normal skin, EGFR is expressed in the basal layer of the epidermis, outer root sheath, eccrine sweat glands, sebaceous glands, etc., and plays an important role in skin proliferation and differentiation. It is thought that increased expression of the EGFR gene promotes normal proliferation of epidermal cells and accelerates epidermal turnover. An example of the nucleotide sequence of the human EGFR gene is the nucleotide sequence registered in the GenBank database under accession number NM_005228. The nucleotide sequence of the EGFR gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as EGFR. The PCNA gene encompasses homologs, paralogs, and orthologs of the human EGFR gene, as long as it encodes a protein that functions as EGFR.

[0020] The "GRHL3 gene" encodes GRHL3 (grainyhead-like transcription factor 3). GRHL3 functions as a transcription factor. Deletion of GRHL3 results in decreased expression of many genes important for skin barrier formation, such as genes encoding lipid-processing enzymes, cell adhesion molecules, and structural proteins. Increased expression of the GRHL3 gene is thought to maintain normal epidermal differentiation and promote epidermal turnover. An example of the nucleotide sequence of the human GRHL3 gene is the nucleotide sequence registered in the GenBank database under accession number NM_001195010. The nucleotide sequence of the GRHL3 gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as GRHL3. The GRHL3 gene encompasses homologs, paralogs, and orthologs of the human GRHL3 gene, as long as they encode a protein that functions as GRHL3.

[0021] The "HBEGF gene" is a gene that encodes HB-EGF (heparin-binding EGF-like growth factor). HB-EGF is an epidermal growth factor with heparin-binding activity. HB-EGF functions as a growth factor for epidermal keratinocytes and as a growth factor necessary for the epithelialization process of wound healing. It is thought that increased expression of the HBEGF gene activates the proliferation of epidermal cells and promotes epidermal turnover. An example of the nucleotide sequence of the human HBEGF gene is the nucleotide sequence registered in the GenBank database under accession number NM_001945. The nucleotide sequence of the HBEGF gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as HB-EGF. The HBEGF gene encompasses homologs, paralogs, and orthologs of the human HBEGF gene, as long as it encodes a protein that functions as HB-EGF.

[0022] As used herein, "enhanced gene expression" refers to an increase in the expression level of a target gene in cells cultured in the presence of the cell activator of this embodiment, compared to the expression level of the target gene in control cells (control group) cultured in the absence of the cell activator of this embodiment. The expression level of a target gene in cells cultured in the presence of the cell activator of this embodiment may be increased by, for example, 1% or more, 3% or more, 5% or more, 10% or more, 15% or more, 20% or more, 25% or more, 30% or more, 35% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, 98% or more, or 100% or more, compared to the expression level of the target gene in the control group.

[0023] Changes in gene expression levels can be confirmed by known methods. For example, a method for measuring gene expression levels can be used, such as transcriptome analysis, which comprehensively obtains transcripts of target genes and enables measurement of the state of gene expression. Specific examples of transcriptome analysis methods include microarrays, real-time PCR (qPCR), RNA-seq, Northern blotting, and in situ hybridization.

[0024] The cell activator of the present embodiment may be used as it is, or may be incorporated into pharmaceuticals or cosmetics for the purpose of imparting cell activating function, or may be incorporated into a cell activating composition described below.

[0025] [Cell stimulating composition] A second aspect of the present invention is a cell activating composition containing naringenin. The cell activating composition contains naringenin as an active ingredient. The cell activating composition may also contain the cell activator according to the first aspect.

[0026] The cell-stimulating composition of this embodiment may contain other ingredients in addition to naringenin. Examples of such other ingredients include pharmaceutically acceptable carriers. A "pharmaceutically acceptable carrier" refers to a carrier that does not inhibit the physiological activity of the active ingredient and is not substantially toxic to the intended recipient. "Substantially non-toxic" means that the ingredient is not toxic to the intended recipient at the amount typically used. Pharmaceutically acceptable carriers include, but are not limited to, oily ingredients, moisturizers, texture enhancers, surfactants, various polymers, thickeners, gelling agents, antioxidants, preservatives, antibacterial agents, chelating agents, pH adjusters, acids and alkalis, powders, UV absorbers, various active ingredients (e.g., whitening agents, anti-inflammatory agents, hair growth agents, blood circulation promoters, stimulants, anti-aging agents), vitamins and their derivatives, hormones, various extracts, fragrances, and coloring materials (dyes, colorants, dyes, pigments).

[0027] Oily components include higher alcohols such as cetanol, myristyl alcohol, oleyl alcohol, lauryl alcohol, cetostearyl alcohol, stearyl alcohol, arachyl alcohol, behenyl alcohol, jojoba alcohol, chimyl alcohol, selachyl alcohol, batyl alcohol, hexyldecanol, isostearyl alcohol, 2-octyldodecanol, and dimer diol; aralkyl alcohols and derivatives such as benzyl alcohol; lauric acid, myristic acid, palmitic acid, stearic acid, and isostearic acid. Higher fatty acids such as behenic acid, undecylenic acid, 12-hydroxystearic acid, palmitoleic acid, oleic acid, linoleic acid, linolenic acid, erucic acid, docosahexaenoic acid, eicosapentaenoic acid, isohexadecanoic acid, anteisohenicosanoic acid, long-chain branched fatty acids, dimer acids, hydrogenated dimer acids, and their aluminum salts, calcium salts, magnesium salts, zinc salts, sodium salts, potassium salts, and other metal soaps, amine salts such as ethanolamine salts, and nitrogen-containing derivatives such as amides; liquid paraffin (mineral oil), heavy liquid isopropyl alcohol, Carbonates such as isoparaffin, light liquid isoparaffin, α-olefin oligomer, polyisobutene, hydrogenated polyisobutene, polybutene, squalane, olive-derived squalane, squalene, petrolatum, and solid paraffin; waxes such as candelilla wax, carnauba wax, rice wax, Japan wax, beeswax, montan wax, ozokerite, ceresin, paraffin wax, microcrystalline wax, petrolatum, Fischer-Tropsch wax, polyethylene wax, and ethylene-propylene copolymer; coconut oil, Vegetable oils and fats such as palm oil, palm kernel oil, safflower oil, olive oil, castor oil, avocado oil, sesame oil, tea oil, evening primrose oil, wheat germ oil, macadamia nut oil, hazelnut oil, kukui nut oil, rosehip oil, meadowfoam oil, persic oil, tea tree oil, peppermint oil, corn oil, rapeseed oil, sunflower oil, wheat germ oil, linseed oil, cottonseed oil, soybean oil, peanut oil, rice bran oil, cocoa butter, shea butter, hydrogenated coconut oil, hydrogenated castor oil, jojoba oil, and hydrogenated jojoba oil; animal oils and fats such as beef tallow, milk fat, horse fat, egg yolk oil, mink oil, and turtle oil;Animal waxes such as spermaceti, lanolin, and orange roughy oil; lanolin derivatives such as liquid lanolin, reduced lanolin, adsorbed purified lanolin, acetated lanolin, acetated liquid lanolin, hydroxylanolin, polyoxyethylene lanolin, lanolin fatty acids, hard lanolin fatty acids, lanolin alcohol, acetated lanolin alcohol, and cetyl lanolyl acetate; lecithin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol. phospholipids such as phosphatidylinositol, sphingomyelin, etc., phosphatidic acid, lysolecithin, etc.; phospholipid derivatives such as hydrogenated soybean phospholipid, partially hydrogenated soybean phospholipid, hydrogenated egg yolk phospholipid, partially hydrogenated egg yolk phospholipid, etc.; sterols such as cholesterol, dihydrocholesterol, lanosterol, dihydrolanosterol, phytosterol, cholic acid, etc.; sapogenins; saponins; cholesteryl acetate, cholesteryl nonanoate , Cholesteryl stearate, Cholesteryl isostearate, Cholesteryl oleate, N-Lauroyl-L-glutamic acid di(cholesteryl / behenyl / octyldodecyl), N-Lauroyl-L-glutamic acid di(cholesteryl / octyldodecyl), N-Lauroyl-L-glutamic acid di(phytosteryl / behenyl / octyldodecyl), N-Lauroyl-L-glutamic acid di(phytosteryl / octyldodecyl), N-Lauroyl sarcosine isopropyl Sterol esters such as acyl sarcosine alkyl esters, cholesteryl 12-hydroxystearate, cholesteryl macadamiate, phytosteryl macadamiate, phytosteryl isostearate, cholesteryl soft lanolinate, cholesteryl hard lanolinate, cholesteryl long-chain branched fatty acids, and cholesteryl long-chain α-hydroxy fatty acids; lipid complexes such as phospholipid-cholesterol complexes and phospholipid-phytosterol complexes;Octyldodecyl myristate, hexyldecyl myristate, octyldodecyl isostearate, cetyl palmitate, octyldodecyl palmitate, cetyl octanoate, hexyldecyl octanoate, isotridecyl isononanoate, isononyl isononanoate, octyl isononanoate, isotridecyl isononanoate, isodecyl neopentanoate, isotridecyl neopentanoate, isostearyl neopentanoate, octyldodecyl neodecanoate, oleyl oleate, octyldodecyl oleate, ricinoleic acid Monoalcohol carboxylic acid esters such as octyldodecyl, lanolin fatty acid octyldodecyl, hexyldecyl dimethyloctanoate, octyldodecyl erucate, hydrogenated castor oil isostearate, ethyl oleate, avocado oil fatty acid ethyl, isopropyl myristate, isopropyl palmitate, octyl palmitate, isopropyl isostearate, lanolin fatty acid isopropyl, and triethyl citrate; oxyacid esters such as cetyl lactate, diisostearyl malate, and hydrogenated castor oil monoisostearate;Glyceryl trioctanoate, glyceryl trioleate, glyceryl triisostearate, glyceryl diisostearate, caprylic / capric triglyceride, caprylic / capric / myristic / stearic triglyceride, hydrogenated rosin triglyceride (hydrogenated ester gum), rosin triglyceride (ester gum), glyceryl behenate eicosandioate, glyceryl tetradecanedioate / eicosandioate, polyglyceryl-10 tetradecanedioate / eicosandioate, trimethylolpropane trioctanoate, trimethylolpropane triisostearate, neopentyl glycol dioctanoate, neopentyl glycol dicaprate, 2-butyl-2-ethyl-1,3-propanediol dioctanoate, 3-methyl-1,5-pentanediol dineopentanoate polyhydric alcohol fatty acid esters such as ethanol, 2,4-diethyl-1,5-pentanediol dineopentanoate, propylene glycol dioleate, pentaerythrityl tetraoctanoate, hydrogenated pentaerythrityl rosin, ditrimethylolpropane triethylhexanoate, ditrimethylolpropane isostearate / sebacic acid, pentaerythrityl triethylhexanoate, dipentaerythrityl hydroxystearate / stearate / rosinate, diglyceryl diisostearate, polyglyceryl tetraisostearate, polyglyceryl-10 nonaisostearate, polyglyceryl-8 deca(erucate / isostearate / ricinoleate), diglyceryl hexyldecanoate / sebacic acid oligoester, glycol distearate (ethylene glycol distearate), etc.;Diisopropyl Dimer Dilinoleate, Diisostearyl Dimer Dilinoleate, Di(isostearyl / phytosteryl) Dimer Dilinoleate, Phytosteryl / Behenyl Dimer Dilinoleate, Phytosteryl / Isostearyl / Cetyl / Stearyl / Behenyl) Dimer Dilinoleate, Dimer Dilinoleyl Dimer Dilinoleate, Dimer Dilinoleyl Bis(phytosteryl / behenyl / isostearyl) Dimer Dilinoleate, Dimer Dilinoleyl Diisostearate, Dimer Dilinoleyl Hydrogenated Rosin Condensate, Hydrogenated Castor Oil Dimer Dilinoleate, Hydroxyalkyl Dimer Derivatives of dimer acid or dimer diol such as immerdilinoleyl ether; fatty acid alkanolamides such as coconut oil fatty acid monoethanolamide (cocamide MEA), coconut oil fatty acid diethanolamide (cocamide DEA), lauric acid monoethanolamide (lauramide MEA), lauric acid diethanolamide (lauramide DEA), lauric acid monoisopropanolamide (lauramide MIPA), palmitic acid monoethanolamide (palmitamide MEA), palmitic acid diethanolamide (palmitamide DEA), and coconut oil fatty acid methylethanolamide (cocamide methyl MEA);Dimethicone (dimethylpolysiloxane), highly polymerized dimethicone (highly polymerized dimethylpolysiloxane), cyclomethicone (cyclic dimethylsiloxane, decamethylcyclopentasiloxane), phenyl trimethicone, diphenyl dimethicone, phenyl dimethicone, stearoxypropyl dimethylamine, (aminoethyl aminopropyl methicone / dimethicone) copolymer, dimethiconol, dimethiconol crosspolymer, silicone resin, silicone rubber, amino-modified silicones such as aminopropyl dimethicone and amodimethicone, cation-modified silicone, polyether-modified silicones such as dimethicone copolyol, polyglycerin Preferred examples of the silicone include silicones such as phosphorus-modified silicone, sugar-modified silicone, carboxylic acid-modified silicone, phosphate-modified silicone, sulfate-modified silicone, alkyl-modified silicone, fatty acid-modified silicone, alkyl ether-modified silicone, amino acid-modified silicone, peptide-modified silicone, fluorine-modified silicone, cation-modified and polyether-modified silicone, amino-modified and polyether-modified silicone, alkyl-modified and polyether-modified silicone, and polysiloxane-oxyalkylene copolymer; and fluorine-based oils such as perfluorodecane, perfluorooctane, and perfluoropolyether.

[0028] Moisturizing agents and feel improvers include polyols and their polymers such as glycerin, 1,3-butylene glycol, propylene glycol, 3-methyl-1,3-butanediol, 1,3-propanediol, 2-methyl-1,3-propanediol, trimethylolpropane, pentaerythritol, hexylene glycol, diglycerin, polyglycerin, diethylene glycol, polyethylene glycol, dipropylene glycol, polypropylene glycol, and ethylene glycol-propylene glycol copolymers; glycol alkyl ethers such as diethylene glycol monoethyl ether (ethoxydiglycol), ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, and diethylene glycol dibutyl ether; sugar alcohols such as sorbitol, xylitol, erythritol, mannitol, and maltitol; glucose, fructose, galactose, mannose, threose, xylose, arabinose, fucose, ribose, deoxyribose, maltose, trehalose, lactose, Natural products include raffinose, gluconic acid, glucuronic acid, β-glucan, chitin, chitosan, heparin and derivatives, pectin, arabinogalactan, dextrin, dextran, glycogen, ethyl glucoside, glucosyl ethyl methacrylate polymers or copolymers, and other sugars and derivatives thereof; hyaluronic acid, sodium hyaluronate; sodium chondroitin sulfate; mucoitin sulfate, caronin sulfate, keratosulfate, dermatan sulfate; Tremella fuciformis extract, Tremella fuciformis polysaccharides; fucoidan; and tuberose polysaccharides. derived polysaccharides; organic acids such as citric acid, tartaric acid, and lactic acid and their salts; urea; 2-pyrrolidone-5-carboxylic acid and its sodium salts, etc.; amino acids such as betaine (trimethylglycine), proline, hydroxyproline, arginine, lysine, serine, glycine, alanine, phenylalanine, tyrosine, β-alanine, threonine, glutamic acid, glutamine, asparagine, aspartic acid, cysteine, cystine, methionine, leucine, isoleucine, valine, tryptophan, histidine, and taurine and their salts;Collagen, fish collagen, atelocollagen, gelatin, elastin, collagen degradation peptides, hydrolyzed collagen, hydroxypropylammonium chloride hydrolyzed collagen, elastin degradation peptides, keratin degradation peptides, hydrolyzed keratin, conchiolin degradation peptides, hydrolyzed conchiolin, silk proteolytic peptides, hydrolyzed silk, sodium lauroyl hydrolyzed silk, soybean proteolytic peptides, wheat proteolytic peptides, hydrolyzed wheat protein, casein degradation peptides, acylated peptides and their derivatives; acylated peptides such as palmitoyl oligopeptide, palmitoyl pentapeptide, palmitoyl tetrapeptide Preferred examples of such ceramides include lactic acid bacteria culture medium, yeast extract, eggshell membrane protein, bovine submandibular gland mucin, hypotaurine, sesame lignan glycoside, glutathione, albumin, whey, choline chloride, phosphorylcholine, animal and plant extracts such as placenta extract, alastin, collagen, witch hazel water, loofah water, chamomile extract, licorice extract, comfrey extract, silk extract, rose rouge extract, yarrow extract, eucalyptus extract, and melilot extract, and natural ceramides (types 1, 2, 3, 4, 5, and 6), hydroxyceramides, pseudoceramides, sphingoglycolipids, ceramides, and glycoceramide-containing extracts.

[0029] Preferred surfactants include anionic surfactants, nonionic surfactants, cationic surfactants, amphoteric surfactants, polymer surfactants, etc. There are no particular limitations on the HLB of the surfactant, and surfactants from as low as about 1 to as high as about 20 can be used, and it is also preferable to combine surfactants with low and high HLBs. Examples of preferred surfactants include anionic surfactants such as fatty acid salts, potassium laurate, and potassium myristate; alkyl sulfate salts, such as sodium lauryl sulfate, triethanolamine lauryl sulfate, and ammonium lauryl sulfate; polyoxyethylene alkyl sulfates, such as sodium laureth sulfate and triethanolamine laureth sulfate; acyl N-methylamino acid salts, such as sodium cocoyl methyl taurate, potassium cocoyl methyl taurate, sodium lauroyl methyl taurate, sodium myristoyl methyl taurate, sodium lauroyl methyl alanine, sodium lauroyl sarcosine, triethanolamine lauroyl sarcosine, and sodium lauroyl methyl alanine glutamate; sodium cocoyl glutamate, triethanolamine cocoyl glutamate, sodium lauroyl glutamate, sodium myristoyl glutamate, sodium stearoyl glutamate, and palmitoyl glutamate. Acyl amino acid salts such as ditriethanolamine aspartate and triethanolamine cocoyl alanine; polyoxyethylene alkyl ether acetates such as sodium laureth acetate; succinate esters such as sodium lauroyl monoethanolamide succinate; fatty acid alkanolamide ether carboxylates; acyl lactates; polyoxyethylene fatty amine sulfates; fatty acid alkanolamide sulfates; fatty acid glyceride sulfates such as sodium hydrogenated coconut oil fatty acid glycerin sulfate; alkyl benzene polyoxyethylene sulfates; olefin sulfonates such as sodium α-olefin sulfonate; alkyl sulfosuccinates such as disodium lauryl sulfosuccinate and dioctyl sodium sulfosuccinate; alkyl ether sulfosuccinates such as disodium laureth sulfosuccinate, sodium monolauroyl monoethanolamide polyoxyethylene sulfosuccinate, and sodium lauryl polypropylene glycol sulfosuccinate;Alkylbenzenesulfonates such as sodium tetradecylbenzenesulfonate and triethanolamine tetradecylbenzenesulfonate; alkylnaphthalenesulfonates; alkanesulfonates; α-sulfofatty acid methyl ester salts; acylisethionates; alkylglycidyl ether sulfonates; alkyl sulfoacetates; alkyl ether phosphate ester salts such as sodium laureth phosphate, sodium dilaureth phosphate, sodium trilaureth phosphate, and sodium monooleth phosphate; alkyl phosphate ester salts such as potassium lauryl phosphate; sodium caseinate; alkylaryl ether phosphates; fatty acid amide ether phosphates; phospholipids such as phosphatidylglycerol, phosphatidylinositol, and phosphatidic acid; silicone-based anionic surfactants such as carboxylic acid-modified silicone, phosphate-modified silicone, and sulfate-modified silicone; and nonionic surfactants such as laureth (polyoxyethylene lauryl ether), ceteth (polyoxyethylene lauryl ether), and Polyoxyethylene alkyl ethers with various polyoxyethylene addition numbers, such as polyoxyethylene cetyl ethers, steareths (polyoxyethylene stearyl ethers), beheneths (polyoxyethylene behenyl ethers), isosteareths (polyoxyethylene isostearyl ethers), and octyldodeceths (polyoxyethylene octyldodecyl ethers); polyoxyethylene alkyl phenyl ethers; castor oil and hydrogenated castor oil derivatives, such as polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil monoisostearate, polyoxyethylene hydrogenated castor oil triisostearate, polyoxyethylene hydrogenated castor oil monopyroglutamic acid monoisostearate diester, and polyoxyethylene hydrogenated castor oil maleic acid; polyoxyethylene phytosterols; polyoxyethylene cholesterol; polyoxyethylene cholestanol; polyoxyethylene lanolin; and polyoxyethylene reduced lanolin.Polyoxyethylene-polyoxypropylene alkyl ethers such as polyoxyethylene-polyoxypropylene cetyl ether, polyoxyethylene-polyoxypropylene 2-decyltetradecyl ether, polyoxyethylene-polyoxypropylene monobutyl ether, polyoxyethylene-polyoxypropylene hydrogenated lanolin, and polyoxyethylene-polyoxypropylene glycerin ether; polyoxyethylene-polyoxypropylene glycol; polyoxyethylene-polyoxypropylene diglyceryl; ) Glycerin polyoxypropylene glycol; glycerin fatty acid partial esters such as glyceryl stearate, glyceryl isostearate, glyceryl palmitate, glyceryl myristate, glyceryl oleate, glyceryl coconut oil fatty acid, glycerin mono-cottonseed oil fatty acid, glycerin mono-erucate, glycerin sesquioleate, glycerin α,α'-oleic acid pyroglutamate, glycerin monostearate malate, etc.; polyglyceryl-2, 3, 4, 5, 6, and 8 stearate , 10, Polyglyceryl-6 distearate, 10, Polyglyceryl-2 tristearate, Polyglyceryl-10 decaisostearate, Polyglyceryl-2 isostearate, 3, 4, 5, 6, 8, 10, Polyglyceryl-2 diisostearate (diglyceryl diisostearate), 3, 10, Polyglyceryl-2 triisostearate, Polyglyceryl-2 tetraisostearate, Polyglyceryl-10 decaisostearate, Polyglyceryl-2 oleate, 3, Nos. 4, 5, 6, 8, and 10, polyglycerin fatty acid esters such as polyglyceryl-6 dioleate, polyglyceryl-2 trioleate, and polyglyceryl-10 decaoleate; ethylene glycol mono-fatty acid esters such as ethylene glycol monostearate; propylene glycol mono-fatty acid esters such as propylene glycol monostearate; pentaerythritol partial fatty acid esters; sorbitol partial fatty acid esters; maltitol partial fatty acid esters; maltitol ethers;Sorbitan fatty acid esters such as sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, sorbitan trioleate, diglycerol sorbitan penta-2-ethylhexylate, and diglycerol sorbitan tetra-2-ethylhexylate; partial esters of sugar derivatives such as sucrose fatty acid esters, methyl glucoside fatty acid esters, and trehalose undecylenate; alkyl glucosides such as caprylyl glucoside; alkyl polyglycols Coside; Lanolin alcohol; Reduced lanolin; Polyoxyethylene fatty acid mono- and diesters such as polyoxyethylene distearate, polyethylene glycol diisostearate, polyoxyethylene monooleate, and polyoxyethylene dioleate; Polyoxyethylene propylene glycol fatty acid esters; Polyoxyethylene glycerin fats such as polyoxyethylene glycerin monostearate, polyoxyethylene glycerin monoisostearate, and polyoxyethylene glycerin triisostearate. Fatty acid esters; polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monooleate, and polyoxyethylene sorbitan tetraoleate; polyoxyethylene sorbitol fatty acid esters such as polyoxyethylene sorbitol monolaurate, polyoxyethylene sorbitol monooleate, polyoxyethylene sorbitol pentaoleate, and polyoxyethylene sorbitol monostearate; polyoxyethylene methyl glucoside fatty acid esters; polyoxyethylene alkyl ether fatty acid esters; polyoxyethylene animal and vegetable oils and fats such as polyoxyethylene sorbitol beeswax; alkyl glyceryl ethers such as isostearyl glyceryl ether, chimyl alcohol, selachyl alcohol, and batyl alcohol; polyhydric alcohol alkyl ethers; polyoxyethylene alkylamines; tetrapolyoxyethylene-tetrapolyoxypropylene-ethylenediamine condensates; natural surfactants such as saponin and sophorolipids; polyoxyethylene fatty acid amides;Fatty acid alkanolamides such as coconut oil fatty acid monoethanolamide (cocamide MEA), coconut oil fatty acid diethanolamide (cocamide DEA), lauric acid monoethanolamide (lauramide MEA), lauric acid diethanolamide (lauramide DEA), lauric acid monoisopropanolamide (lauramide MIPA), palmitic acid monoethanolamide (palmitamide MEA), palmitic acid diethanolamide (palmitamide DEA), coconut oil fatty acid methylethanolamide (cocamide methyl MEA), etc.; lauramine oxide Alkyl dimethylamine oxides such as cocamine oxide, stearamine oxide, and behenamine oxide; alkyl ethoxydimethylamine oxide; polyoxyethylene alkyl mercaptan; silicone-based nonionic surfactants such as polyether-modified silicones such as dimethicone copolyol, polysiloxane-oxyalkylene copolymers, polyglycerin-modified silicones, and sugar-modified silicones; cationic surfactants include behentrimonium chloride, steartrimonium chloride, cetrimonium chloride, and lauryltrimonium chloride. alkyltrimethylammonium chlorides such as ammonium chloride; alkyltrimethylammonium bromides such as stearyltrimonium bromide; dialkyldimethylammonium chlorides such as distearyldimonium chloride and dicocodimonium chloride; fatty acid amidoamines and their salts such as stearamidopropyldimethylamine and stearamidoethyldiethylamine; alkyl ether amines and their salts or quaternary salts such as stearoxypropyldimethylamine; fatty acid amide quaternary ammonium salts such as ethyl sulfate of long-chain branched fatty acid (12-31) aminopropylethyldimethylammonium and ethyl sulfate of lanolin fatty acid aminopropylethyldimethylammonium; polyoxyethylene alkylamines and their salts or quaternary salts; alkylamine salts; fatty acid amide guanidinium salts; alkyl ether amine ammonium salts; alkyl trialkylene glycol ammonium salts; benzalkonium salts; benzethonium salts; pyridinium salts such as cetylpyridinium chloride; imidazolinium salts; alkylisoquinolinium salts; dialkylmorphonium salts; polyamine fatty acid derivatives;Silicone-based cationic surfactants such as amino-modified silicones such as aminopropyl dimethicone and amodimethicone, cation-modified silicones, cation-modified and polyether-modified silicones, and amino-modified and polyether-modified silicones; amphoteric surfactants include N-alkyl-N,N-dimethyl amino acid betaines such as lauryl betaine (lauryl dimethyl amino acetate betaine); fatty acid amidoalkyl-N,N-dimethyl amino acid betaines such as cocamidopropyl betaine and lauramidopropyl betaine; imidazoline-type betaines such as sodium cocoamphoacetate and sodium lauroamphoacetate; alkyl sulfobetaines such as alkyldimethyltaurine; sulfate-type betaines such as alkyldimethylaminoethanol sulfate esters; phosphate-type betaines such as alkyldimethylaminoethanol phosphate esters; sphingolipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and sphingomyelin; Preferred examples of suitable surfactants include phospholipids such as lecithin, lysolecithin, hydrogenated soybean phospholipid, partially hydrogenated soybean phospholipid, hydrogenated egg yolk phospholipid, partially hydrogenated egg yolk phospholipid, and hydroxide lecithin; silicone-based amphoteric surfactants; and polymer surfactants such as polyvinyl alcohol, sodium alginate, starch derivatives, tragacanth gum, acrylic acid / alkyl methacrylate copolymer, and 2-methacryloyloxyethyl phosphorylcholine / stearyl methacrylate copolymer; and various silicone-based surfactants.

[0030] Various polymers, thickeners, and gelling agents include guar gum, locust bean gum, queen seed, carrageenan, galactan, gum arabic, tara gum, tamarind, furcellaran, karaya gum, aoi, caragam, tragacanth gum, pectin, pectinic acid and salts such as sodium salt, alginic acid and salts such as sodium salt, mannan; starch from rice, corn, potato, wheat, etc.; xanthan gum, dextran, succinoglucan, curdlan, hyaluronic acid and its salt, xanthan gum, pullulan, gellan gum, chitin, chitosan cellulose, agar, cassou extract, chondroitin sulfate, casein, collagen, gelatin, albumin; cellulose and its derivatives such as methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose and its sodium salts, methylhydroxypropyl cellulose, sodium cellulose sulfate, dialkyldimethylammonium cellulose sulfate, crystalline cellulose, cellulose powder; soluble starch, carboxymethyl starch, methylhydroxypropyl starch, methyl starch, etc. Starch-based polymers, starch derivatives such as hydroxypropyltrimonium starch chloride and corn starch aluminum octenylsuccinate; alginic acid derivatives such as sodium alginate and propylene glycol alginate; polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), vinylpyrrolidone-vinyl alcohol copolymer, polyvinyl methyl ether; polyethylene glycol, polypropylene glycol, polyoxyethylene-polyoxypropylene copolymer; amphoteric methacrylate copolymers such as (methacryloyloxyethyl carboxybetaine / alkyl methacrylate) copolymer and (acrylates / stearyl acrylate / ethylamine oxide methacrylate) copolymer; (dimethicone / vinyl dimethicone) crosspolymer, (alkyl acrylate / diacetone acrylamide) copolymer, (alkyl acrylate / diacetone acrylamide) copolymer AMP; partially saponified polyvinyl acetate, maleic acid copolymer; vinylpyrrolidone-dialkylaminoalkyl methacrylate copolymer; acrylic resins with alkanolamine; polyesters, water-dispersible polyesters;Polyacrylamide; polyacrylic acid ester copolymers such as polyethyl acrylate, carboxyvinyl polymers, polyacrylic acid and its salts such as sodium salt, acrylic acid-methacrylic acid ester copolymers; acrylic acid-alkyl methacrylate copolymers; cationized cellulose such as Polyquaternium-10, diallyldimethylammonium chloride-acrylamide copolymers such as Polyquaternium-7, acrylic acid-diallyldimethylammonium chloride copolymers such as Polyquaternium-22, acrylic acid-diallyldimethylammonium chloride-acrylamide copolymers such as Polyquaternium-39, acrylic acid-cationized methacrylic acid ester copolymers, acrylic acid-cationized methacrylic acid amide copolymers, acrylic acid-methyl acrylate-methacrylamidopropyltrimethylammonium chloride copolymers such as Polyquaternium-47, methacrylic acid choline ester chloride polymers; cationized oligosaccharides, cationized dextran, cationized guar hydroxypropyltrimonium chloride, etc. Preferred examples of the polymer include polysaccharides, polyethyleneimine, cationic polymers, 2-methacryloyloxyethyl phosphorylcholine polymers such as polyquaternium-51 and copolymers with butyl methacrylate copolymers, polymer emulsions such as acrylic resin emulsions, polyethyl acrylate emulsions, polyacrylic alkyl ester emulsions, polyvinyl acetate resin emulsions, natural rubber latex, and synthetic latex; nitrocellulose; polyurethanes and various copolymers; various silicones; various silicone copolymers such as acrylic-silicone graft copolymers; various fluorine-containing polymers; 12-hydroxystearic acid and its salts; dextrin fatty acid esters such as dextrin palmitate and dextrin myristate; silicic anhydride, fumed silica (ultrafine silicic anhydride particles), aluminum magnesium silicate, sodium magnesium silicate, metal soaps, dialkyl phosphate metal salts, bentonite, hectorite, organically modified clay minerals, sucrose fatty acid esters, and fructooligosaccharide fatty acid esters.

[0031] Preferred antioxidants include α-lipoic acid, α-lipoic acid salts, and α-lipoic acid derivatives; tocopherol derivatives such as tocopherol (vitamin E), tocotrienol, and tocopherol acetate; BHT, BHA; gallic acid derivatives such as propyl gallate; vitamin C (ascorbic acid) and / or its derivatives; erythorbic acid and its derivatives; sulfites such as sodium sulfite; bisulfites such as sodium bisulfite; thiosulfates such as sodium thiosulfate; metabisulfites; thiotaurine, hypotaurine; thioglycerol, thiourea, thioglycolic acid, and cysteine ​​hydrochloride. Preferred reducing agents include thioglycolic acid, cysteine, and cysteamine. Preferred oxidizing agents include hydrogen peroxide, ammonium persulfate, sodium bromate, and percarbonate.

[0032] Examples of preservatives and antibacterial agents include hydroxybenzoic acids and their salts or esters such as methylparaben, ethylparaben, propylparaben, and butylparaben; salicylic acid; sodium benzoate; phenoxyethanol; 1,2-diols such as 1,2-pentanediol and 1,2-hexanediol; isothiazolinone derivatives such as methylchloroisothiazolinone and methylisothiazolinone; imidazolinium urea; dehydroacetic acid and its salts; phenols; halogenated bisphenols such as triclosan; and acid amines. Preferred examples of the antibacterial agent include amides, quaternary ammonium salts; trichlorocarbanide, zinc pyrithione, benzalkonium chloride, benzethonium chloride, sorbic acid, chlorhexidine, chlorhexidine gluconate, halocarban, hexachlorophene, hinokitiol; other phenols such as phenol, isopropylphenol, cresol, thymol, parachlorophenol, phenylphenol, and phenylphenol sodium; phenylethyl alcohol, photosensitizers, antibacterial zeolites, and silver ions.

[0033] Preferred examples of the chelating agent include edetates (ethylenediaminetetraacetates) such as EDTA, EDTA2Na, EDTA3Na, and EDTA4Na; hydroxyethylethylenediaminetriacetates such as HEDTA3Na; pentetates (diethylenetriaminepentaacetate); phytic acid; phosphonic acids such as etidronic acid and salts thereof such as sodium salts; sodium oxalate; polyamino acids such as polyaspartic acid and polyglutamic acid; sodium polyphosphate, sodium metaphosphate, phosphoric acid; sodium citrate, citric acid, alanine, dihydroxyethylglycine, gluconic acid, ascorbic acid, succinic acid, and tartaric acid.

[0034] Preferred examples of the pH adjuster and acid / alkali include citric acid, sodium citrate, lactic acid, sodium lactate, glycolic acid, succinic acid, acetic acid, sodium acetate, malic acid, tartaric acid, fumaric acid, phosphoric acid, hydrochloric acid, sulfuric acid, monoethanolamine, diethanolamine, triethanolamine, isopropanolamine, triisopropanolamine, 2-amino-2-methyl-1,3-propanediol, 2-amino-2-hydroxymethyl-1,3-propanediol, arginine, sodium hydroxide, potassium hydroxide, aqueous ammonia, guanidine carbonate, and ammonium carbonate.

[0035] Powders include mica, talc, kaolin, sericite, montmorillonite, kaolinite, mica, muscovite, phlogopite, synthetic mica, lepidolite, biotite, vermiculite, magnesium carbonate, calcium carbonate, aluminum silicate, barium silicate, calcium silicate, magnesium silicate, strontium silicate, metal tungstate, magnesium, zeolite, barium sulfate, calcined calcium sulfate, calcium phosphate, fluorapatite, hydroxyapatite, ceramic powder, bentonite, smectite, clay, mud, metal soaps (e.g., zinc myristate, calcium palmitate, aluminum stearate), calcium carbonate, red iron oxide, yellow iron oxide, black iron oxide, ultramarine, Prussian blue, carbon black, titanium oxide, fine and ultrafine titanium oxide particles, zinc oxide, fine and ultrafine zinc oxide particles, alumina, silica, fumed silica (ultrafine silicic anhydride particles), titanium mica Preferred examples include inorganic powders of various sizes and shapes, such as fish scale foil, boron nitride, photochromic pigments, synthetic fluorine-containing phlogopite, fine particle composite powders, gold, and aluminum, and inorganic powders obtained by treating these with silicones such as hydrogen silicone and cyclic hydrogen silicone, or other silanes, or various surface treatment agents such as titanium coupling agents to make them hydrophobic or hydrophilic; organic powders of various sizes and shapes, such as starch, cellulose, nylon powder, polyethylene powder, polymethyl methacrylate powder, polystyrene powder, styrene-acrylic acid copolymer resin powder, polyester powder, benzoguanamine resin powder, polyethylene terephthalate-polymethyl methacrylate laminate powder, polyethylene terephthalate-aluminum-epoxy laminate powder, urethane powder, silicone powder, and Teflon (registered trademark) powder, as well as surface-treated powders and organic-inorganic composite powders.Preferred examples of inorganic salts include sodium chloride-containing salts such as table salt, regular salt, rock salt, sea salt, and natural salt; potassium chloride, aluminum chloride, calcium chloride, magnesium chloride, bittern, zinc chloride, and ammonium chloride; sodium sulfate, aluminum sulfate, aluminum-potassium sulfate (alum), aluminum-ammonium sulfate, barium sulfate, calcium sulfate, potassium sulfate, magnesium sulfate, zinc sulfate, iron sulfate, and copper sulfate; and sodium phosphates such as mono-, di-, and tri-Na phosphate, potassium phosphates, calcium phosphates, and magnesium phosphates.

[0036] Examples of ultraviolet absorbers include benzoic acid-based ultraviolet absorbers such as para-aminobenzoic acid, para-aminobenzoic acid monoglycerin ester, N,N-dipropoxypara-aminobenzoic acid ethyl ester, N,N-diethoxypara-aminobenzoic acid ethyl ester, N,N-dimethylpara-aminobenzoic acid ethyl ester, N,N-dimethylpara-aminobenzoic acid butyl ester, and N,N-dimethylpara-aminobenzoic acid ethyl ester; anthranilic acid-based ultraviolet absorbers such as homomenthyl-N-acetylanthranilate; salicylic acid-based ultraviolet absorbers such as salicylic acid and its sodium salt, amyl salicylate, menthyl salicylate, homomenthyl salicylate, octyl salicylate, phenyl salicylate, benzyl salicylate, and p-isopropanol phenyl salicylate; octyl cinnamate, Cinnamic acid-based UV absorbers such as ethyl 4-isopropyl cinnamate, methyl 2,5-diisopropyl cinnamate, ethyl 2,4-diisopropyl cinnamate, methyl 2,4-diisopropyl cinnamate, propyl p-methoxycinnamate, isopropyl p-methoxycinnamate, isoamyl p-methoxycinnamate, 2-ethylhexyl p-methoxycinnamate (octyl p-methoxycinnamate), 2-ethoxyethyl p-methoxycinnamate (cinoxate), cyclohexyl p-methoxycinnamate, ethyl α-cyano-β-phenylcinnamate, 2-ethylhexyl α-cyano-β-phenylcinnamate (octocurine), glyceryl mono-2-ethylhexanoyl di-paramethoxycinnamate, ferulic acid and its derivatives;Benzophenone-based UV absorbers such as 2,4-dihydroxybenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone, 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, 2,2',4,4'-tetrahydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone (oxybenzone-3), 2-hydroxy-4-methoxy-4'-methylbenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonate, 4-phenylbenzophenone, 2-ethylhexyl-4'-phenyl-benzophenone-2-carboxylate, 2-hydroxy-4-n-octoxybenzophenone, and 4-hydroxy-3-carboxybenzophenone; 3-(4'-methylbenzylidene)-d,l-camphor, 3-benzylidene-d,l-camphor; 2-phenyl-5-methylbenzoxazole; 2,2'-hydroxy-5-methylphenylbenzotriazole; 2-(2'-hydroxy 2-(2'-hydroxy-5'-methylphenylbenzotriazole; Dibenzalazine; Dianisoylmethane; 5-(3,3-dimethyl-2-norbornylidene)-3-pentan-2-one; Dibenzoylmethane derivatives such as 4-t-butylmethoxydibenzoylmethane; Octyltriazone; Urocanic acid derivatives such as urocanic acid and ethyl urocanate; 2-(2'-hydroxy-5'-methylphenyl)benzotriazole Preferred examples thereof include hydantoin derivatives such as 1-(3,4-dimethoxyphenyl)-4,4-dimethyl-1,3-pentanedione, 2-ethylhexyl dimethoxybenzylidene dioxoimidazolidinepropionate, phenylbenzimidazolazole sulfonic acid, terephthalylidene dicamphor sulfonic acid, drometrizole trisiloxane, methyl anthranilate, rutin and its derivatives, and oryzanol and its derivatives;

[0037] Preferred examples of the whitening agent include ascorbic acid, ascorbic acid phosphate salts such as sodium ascorbyl phosphate and magnesium ascorbyl phosphate, ascorbic acid fatty acid esters such as ascorbic acid tetraisopalmitate, ascorbic acid alkyl ethers such as ascorbic acid ethyl ether, ascorbic acid glucoside and its fatty acid esters such as ascorbic acid-2-glucoside, ascorbic acid derivatives such as ascorbic acid sulfate and tocopheryl ascorbyl phosphate; and plant extracts such as kojic acid, ellagic acid, tranexamic acid and derivatives thereof, ferulic acid and derivatives thereof, placenta extract, glutathione, oryzanol, butylresorcinol, oil-soluble chamomilla extract, oil-soluble licorice extract, Nishikawa willow extract, and saxifrage extract.

[0038] Preferred examples of the anti-inflammatory agent include glycyrrhizinic acid and its derivatives, glycyrrhetinic acid derivatives, salicylic acid derivatives, hinokitiol, guaiazulene, allantoin, indomethacin, zinc oxide, hydrocortisone acetate, prednisone, diphedramine hydrochloride, chlorpheniramine maleate; and plant extracts such as peach leaf extract and mugwort leaf extract.

[0039] Preferred examples of hair growth agents, blood circulation promoters, and stimulants include plant extracts and tinctures such as Swertia japonica extract, capsicum tincture, ginger tincture, ginger extract, and cantharis tincture; capsaicin, nonylic acid valenylamide, zingerone, ichthammol, tannic acid, borneol, cyclandelate, cinnarizine, tolazoline, acetylcholine, verapamil, cepharanthine, γ-oryzanol, cepharanthine, vitamin E, and derivatives thereof such as tocopherol nicotinate and tocopherol acetate, γ-oryzanol, nicotinic acid, and derivatives thereof such as nicotinamide, nicotinic acid benzyl ester, inositol hexanicotinate, and nicotine alcohol, allantoin, photosensitizer 301, photosensitizer 401, capronium chloride, pentadecanoic acid monoglyceride, flavanonol derivatives, stigmasterol or stigmastanol and their glycosides, and minoxidil.

[0040] Other medicinal agents such as anti-wrinkle agents, anti-aging agents, firming agents, cooling agents, warming agents, wound healing promoters, irritation soothing agents, analgesics, and cell activators include retinols, retinoic acids, and tocopheryl retinoate; lactic acid, glycolic acid, gluconic acid, fruit acids, salicylic acid, and their derivatives such as glycosides and esters; α- or β-hydroxy acids and their derivatives such as hydroxycapric acid, long-chain α-hydroxy fatty acids, and long-chain α-hydroxy fatty acid cholesteryl; γ-aminobutyric acid, γ-amino-β-hydroxybutyric acid; carnitine; carnosine; creatine; ceramides; sphingosines; caffeine, xanthine, and their derivatives; coenzyme Q10, carotene, lycopene, astaxanthin, lutein, etc. Preferred examples include antioxidants and active oxygen scavengers such as catechins; flavones such as quercetin; isoflavones; gallic acid and ester sugar derivatives; polyphenols such as tannin, sesamin, protoanthocyanidin, chlorogenic acid, and apple polyphenols; rutin and its derivatives; hesperidin and its derivatives; lignan glycosides; licorice extract-related substances such as glabridin, glabrene, liquiritin, and isoliquiritin; lactoferrin; shogaol, gingerol; fragrance substances and their derivatives such as menthol, camphor, and cedrol; capsaicin, vanillin, and their derivatives; insect repellents such as diethyltoluamide; and complexes of physiologically active substances and cyclodextrins.

[0041] Examples of antipruritic agents include diphenhydramine hydrochloride, chlorpheniramine maleate, camphor, substance P inhibitors, etc. Examples of keratin exfoliating / dissolving agents include salicylic acid, sulfur, resorcinol, selenium sulfide, pyridoxine, etc. Examples of antiperspirants include aluminum chlorohydrate, aluminum chloride, zinc oxide, zinc paraphenolsulfonate, etc. Examples of cooling agents include menthol and methyl salicylate, etc. Examples of astringents include citric acid, tartaric acid, lactic acid, aluminum potassium sulfate, tannic acid, etc. Examples of enzymes include superoxide dismutase, catalase, lysozyme chloride, lipase, papain, pancreatin, protease, etc. Examples of nucleic acids include ribonucleic acid and salts thereof, deoxyribonucleic acid and salts thereof, and adenosine triphosphate disodium, etc.

[0042] Vitamins and their derivatives include vitamin A such as retinol, retinol acetate, and retinol palmitate; vitamin B such as thiamine hydrochloride, thiamine sulfate, riboflavin, riboflavin acetate, pyridoxine hydrochloride, pyridoxine dioctanoate, pyridoxine dipalmitate, flavin adenine dinucleotide, cyanocobalamin, folic acids, nicotinic acids such as nicotinamide and benzyl nicotinate, and choline; vitamin C such as ascorbic acid and its sodium salts; vitamin D; vitamin E such as α-, β-, γ-, and δ-tocopherol; other vitamins such as pantothenic acid and biotin; and vitamin B such as ascorbic acid phosphate sodium salt and ascorbic acid phosphate magnesium salt. Preferred examples include ascorbic acid phosphate salts, ascorbic acid fatty acid esters such as ascorbic acid tetraisopalmitate, ascorbyl stearate, ascorbyl palmitate, and ascorbyl dipalmitate, ascorbic acid alkyl ethers such as ascorbic acid ethyl ether, ascorbic acid glucoside and its fatty acid esters such as ascorbic acid-2-glucoside, and ascorbic acid derivatives such as tocopheryl ascorbyl phosphate; vitamin derivatives such as tocopherol nicotinate, tocopherol acetate, tocopherol linoleate, tocopherol ferulate, and tocopherol phosphate; tocotrienols; and various other vitamin derivatives.

[0043] Preferred examples of hormones include estradiol, estrone, ethinylestradiol, cortisone, hydrocortisone, and prednisone.

[0044] Various extracts of plants, animals, microorganisms, etc. include iris extract, angelica extract, dolabrata extract, asparagus extract, avocado extract, hydrangea extract, almond extract, althea extract, arnica extract, apricot extract, apricot kernel extract, ginkgo extract, chinko extract, fennel extract, turmeric extract, oolong tea extract, uva-ursi extract, angelica tree extract, echinacea leaf extract, emmeiso extract, scutellaria root extract, phellodendron bark extract, coptis japonica extract, barley extract, ginseng extract, St. John's wort extract, and nettle extract. Grass extract, Ononis extract, Netherlands mustard extract, orange extract, dried seawater, seaweed extract, oyster leaf extract, oak extract, hydrolyzed elastin, hydrolyzed wheat powder, hydrolyzed silk, Pueraria root extract, chamomilla extract, oil-soluble chamomilla extract, carrot extract, artemisia capillaris extract, oat extract, kalk extract, licorice extract, oil-soluble licorice extract, kiwi extract, angelica tree extract, wood ear extract, cinchona extract, cucumber extract, paulownia leaf extract, guanosine, guava extract, lily of the valley extract, gardenia extract, kumazasa extract , Sophora flavescens extract, walnut extract, chestnut extract, grapefruit extract, clematis extract, black rice extract, brown sugar extract, black vinegar, chlorella extract, mulberry extract, gentian extract, geranium extract, black tea extract, yeast extract, magnolia bark extract, coffee extract, burdock extract, rice extract, fermented rice extract, fermented rice bran extract, rice germ oil, comfrey extract, collagen, cowberry extract, Chinese radish extract, Bupleurum Root extract, umbilical cord extract, saffron extract, salvia extract, soapwort extract, bamboo grass extract, hawthorn extract, Chinese radish extract , Zanthoxylum extract, Shiitake mushroom extract, Rehmannia root extract, Lithospermum root extract, Perilla extract, Tilia extract, Meadowsweet extract, Jatoba extract, Peony extract, Angelica root extract, Calamus root extract, Birch extract, White wood ear extract, Horsetail extract, Stevia extract, Stevia fermented product, Nishikawa willow extract, Ivy extract, Hawthorn extract, Elderberry extract, Yarrow extract, Peppermint extract, Sage extract, Mallow extract, Cnidium extract, Swertia japonica extract, Sophora japonica extract, Rhubarb extract,Soybean extract, Chinese laurel extract, thyme extract, dandelion extract, lichen extract, tea extract, clove extract, Imperata cylindrica extract, tangerine extract, tea tree oil, sweet tea extract, chili pepper extract, angelica extract, calendula extract, peach kernel extract, spruce extract, Houttuynia cordata extract, tomato extract, natto extract, carrot extract, garlic extract, wild rose extract, hibiscus extract, burdock extract, lotus extract, parsley extract, birch extract, honey, witch hazel extract, parietaria extract, jasmine extract, bisabolol, cypress extract, bifidobacteria extract, loquat extract, coltsfoot extract, butterbur shoot extract, poria cocos extract, butcher's broom extract, grape extract Examples of extracts that can be used include ginseng, grape seed extract, propolis, loofah extract, safflower extract, peppermint extract, linden extract, peony extract, hop extract, squid extract, pine extract, horse chestnut extract, skunk cabbage extract, soapberry extract, melissa extract, mozuku extract, peach extract, cornflower extract, eucalyptus extract, saxifrage extract, lily extract, coix seed extract, mugwort extract, lavender extract, green tea extract, eggshell membrane extract, apple extract, rooibos tea extract, lychee extract, lettuce extract, lemon extract, forsythia extract, astragalus extract, rose extract, rosemary extract, Roman chamomile extract, royal jelly extract, and burnet extract.

[0045] Fragrance: acetyl cedrene, amyl cinnamaldehyde, allyl amyl glycolate, β-ionone, isoe super, isobutylquinoline, iris oil, iron, indole, ylang-ylang oil, undecanal, undecenal, γ-undecalactone, estragole, eugenol, oakmoss, opoponax resinoid, orange oil, eugenol, aurantiol, galacsolids, carvacrol, L-carvone, camphor, cannon, carrot seed oil, clove oil, methyl cinnamate, geraniol, geranyl nitrile, isobornyl acetate, geranyl acetate, dimethylbenzylcarbinyl acetate, styraryl acetate, cedryl acetate, terpineol acetate, pt-butylcyclohexyl acetate Al, vetiveryl acetate, benzyl acetate, linalyl acetate, isopentyl salicylate, benzyl salicylate, sandalwood oil, santalol, cyclamen aldehyde, cyclopentadecanolide, methyl dihydrojasmonate, dihydromyrcenol, jasmine absolute, jasmine lactone, cis-jasmone, citral, citronenol, citronellal, cinnamon bark oil, 1,8-cineole, cinnamaldehyde, styrax resinoid, cedarwood oil, cedrene, cedrol, celery seed oil, thyme oil, damascone, damascenone, thymol, tuberose absolute, decanal, decalactone, terpineol, gamma-terpinene, tripluran, nerol, nonanal, 2,6-Nonadienol, Nonalactone, Patchouli Alcohol, Vanilla Absolute, Vanillin, Basil Oil, Patchouli Oil, Hydroxycitronellal, Alpha-Pinene, Piperitone, Phenethyl Alcohol, Phenylacetaldehyde, Petitgrain Oil, Hexyl Cinnamaldehyde, cis-3-Hexenol, Balsam of Peru, Vetiver Oil, Vetiverol, Peppermint Oil, Pepper Oil, Heliotropin, Bergamot Oil, Benzyl Benzene Preferred examples of the fragrance include synthetic and natural fragrances such as maltodextrin, borneol, myrrhizoid, musk ketone, methylnonylacetaldehyde, γ-methylionone, menthol, L-menthol, L-menthone, eucalyptus oil, β-ionone, lime oil, lavender oil, D-limonene, linalool, lyral, lilial, lemon oil, rose absolute, rose oxide, rose oil, rosemary oil, and various essential oils, as well as various blended fragrances.

[0046] Colorants, dyes, and pigments include Brown No. 201, Black No. 401, Purple No. 201, Purple No. 401, Blue No. 1, Blue No. 2, Blue No. 201, Blue No. 202, Blue No. 203, Blue No. 204, Blue No. 205, Blue No. 403, Blue No. 404, Green No. 201, Green No. 202, Green No. 204, Green No. 205, Green No. 3, Green No. 401, Green No. 402, and Red Color No. 102, Red No. 104-1, Red No. 105-1, Red No. 106, Red No. 2, Red No. 201, Red No. 202, Red No. 203, Red No. 204, Red No. 205, Red No. 206, Red No. 207, Red No. 208, Red No. 213, Red No. 214, Red No. 215, Red No. 218, Red No. 219, Red No. 220, Red No. 221, Red No. 223, Red No. 22 No. 5, Red No. 226, Red No. 227, Red No. 228, Red No. 230-1, Red No. 230-2, Red No. 231, Red No. 232, Red No. 3, Red No. 401, Red No. 404, Red Color No. 405, Red No. 501, Red No. 502, Red No. 503, Red No. 504, Red No. 505, Red No. 506, Orange No. 201, Orange No. 203, Orange No. 204, Orange No. 205, Orange No. 206, Orange No. 207, Orange No. 401, Orange No. 402, Orange No. 403, Yellow No. 201, Yellow No. 202-1, Yellow No. 202-2, Yellow No. 203, Yellow No. 204, Yellow Legal dyes such as No. 205, Yellow No. 4, Yellow No. 401, Yellow No. 402, Yellow No. 403-1, Yellow No. 404, Yellow No. 405, Yellow No. 406, Yellow No. 407, Yellow No. 5; Acid Other acidic dyes such as Red 14; Basic dyes such as Arianor Sienna Brown, Arianor Madder Red, Arianor Steel Blue, Arianor Straw Yellow; HC Yellow 2, HC Yellow 5, HC Red 3, 4-hydroxypropylamino-3-nitrophenol, N,N'-bis(2-hydroxyethyl)-2-nitro-p- Nitro dyes such as phenylenediamine, HC Blue 2, and Basic Blue 26; disperse dyes; inorganic white pigments such as titanium dioxide and zinc oxide; inorganic red pigments such as iron oxide (red iron oxide) and iron titanate; inorganic brown pigments such as gamma-iron oxide; inorganic yellow pigments such as yellow iron oxide and ochre; inorganic black pigments such as black iron oxide and low-order titanium oxide; inorganic purple pigments such as mango violet and cobalt violet; inorganic green pigments such as chromium oxide, chromium hydroxide, and cobalt titanate; inorganic blue pigments such as ultramarine and iron blue; titanium dioxide-coated mica, titanium dioxide-coated oxy Pearl pigments such as bismuth chloride, titanium dioxide-coated talc, colored titanium dioxide-coated mica, bismuth oxychloride, and fish scale foil; aluminum powder, copper powder, gold, and other metal powder pigments; surface-treated inorganic and metal powder pigments; Red No. 201, Red No. 202, Red No. 204, Red No. 205, Red No. 220, Red No. 226, Red No. 228, Red No. 405, Orange No. 203, Orange No. 204, Yellow No. 205, Yellow No. 401, Blue No. 404, Red No. 3, Red No. 104, Red No. 106, and Red No. 22 Organic pigments such as zirconium, barium or aluminum lakes, such as No. 7, Red 230, Red 401, Red 505, Orange 205, Yellow 4, Yellow 5, Yellow 202, Yellow 203, Green 3, and Blue 1; surface-treated organic pigments; anthraquinones such as astaxanthin and alizarin, anthocyanidins, β-carotene, catenal, capsanthin, chalcone, carthamine, quercetin, crocin, chlorophyll, curcumin, cochineal, and shikonin, naphthoquinones, bixylanthus, benzoin, benzoyl benzoates ... Preferred examples thereof include natural pigments and dyes such as amines, flavones, betacyanidin, henna, hemoglobin, lycopene, riboflavin, and rutin; oxidation dye intermediates and couplers such as p-phenylenediamine, toluene-2,5-diamine, o-, m-, or p-aminophenol, m-phenylenediamine, 5-amino-2-methylphenol, resorcinol, 1-naphthol, 2,6-diaminopyridine, and salts thereof; autoxidation dyes such as indoline; and dihydroxyacetone.

[0047] The other ingredients may be ingredients listed in the Cosmetic Ingredient Standards, Cosmetic Type Ingredient Standards, Japan Cosmetic Industry Association Ingredient Labeling Name List, INCI Dictionary (The International Cosmetic Ingredient Dictionary and Handbook), Quasi-drug Ingredient Standards, Japanese Pharmacopoeia, Pharmaceutical Additive Standards, and Food Additives Official Specification, as well as known cosmetic ingredients and pharmaceutical ingredients, etc. The above-mentioned ingredients can be contained in the cell-stimulating composition of this embodiment to the extent that the cell-stimulating effect of naringenin can be obtained.

[0048] The cell-stimulating composition of this embodiment may contain an effective amount of naringenin. "An effective amount" refers to the amount of naringenin that is effective for the cell-stimulating effect of naringenin to be exerted. The effective amount may vary depending on the age, sex, weight, etc. of the subject. In the cell-stimulating composition of this embodiment, the effective amount of naringenin is, for example, 0.001 to 10% by mass, 0.01 to 5% by mass, 0.01 to 1% by mass, 0.01 to 0.5% by mass, or 0.01 to 0.1% by mass, as the content of naringenin in the cell-stimulating composition.

[0049] The dosage form of the cell-stimulating composition of this embodiment is not particularly limited, and examples of dosage forms of the cell-stimulating composition of this embodiment include ampoules, capsules, pills, tablets, powders, granules, solids, liquids, gels, bubbles, emulsions, sheets, mists, sprays, and the like.

[0050] The cell-stimulating composition of the present embodiment may be a pharmaceutical product, a quasi-drug, or a cosmetic. The cell-stimulating composition of the present embodiment is preferably a skin topical preparation. The cell-stimulating composition of the present embodiment is preferably a cosmetic, and more preferably a skin cosmetic.

[0051] When the cell stimulating composition of this embodiment is a cosmetic, examples thereof include basic cosmetics such as lotion, emulsion, cream, ointment, lotion, oil, and pack; skin cleansing products such as face wash and body cleanser; massage cosmetics such as massage agents; cleansing cosmetics such as cleansing agents; body hair treatment cosmetics such as depilatories and hair removers; shaving cosmetics such as shaving treatment products, aftershave lotion, pre-shave lotion, and shaving cream; makeup cosmetics such as foundation, lipstick, blush, eye shadow, eyeliner, and mascara; and other topical cosmetics such as perfumes, nail enamel, nail enamel remover, poultices, plasters, tapes, sheets, patches, and aerosols. The cell-stimulating composition of the present embodiment may be a preparation for scalp and / or hair. Examples of scalp and / or hair preparations include shampoos, rinses, hair treatments, pre-hair treatments, permanent solutions, hair dyes, hair styling products, hair tonics, hair growth and tonics, scalp poultices, scalp plasters, scalp tapes, scalp sheets, scalp patches, and aerosols for hair or scalp. The cell-stimulating composition of the present embodiment may also be a bath additive to be added to bathwater. The cell-stimulating composition of the present embodiment may also be used in anti-armpit odor agents, deodorants, deodorants, antiperspirants, sanitary products, sanitary cotton, wet tissues, toothpastes, mouth fresheners, mouthwashes, dishwashing agents, and the like.

[0052] The cell-stimulating composition of this embodiment contains naringenin as an active ingredient, thereby exhibiting a cell-stimulating effect. Furthermore, the cell-stimulating composition contains naringenin as an active ingredient, thereby enhancing the expression of at least one gene selected from the group consisting of KRT14, PCNA, EGFR, GRHL3, and HBEGF. Enhanced expression of these genes is thought to promote normal cell proliferation and cell turnover. The cell-stimulating composition of the present embodiment has a cell-stimulating effect and can therefore be used to improve and / or prevent skin wrinkles, skin firmness, etc. The cell-stimulating composition of the present embodiment can also be used for skin anti-aging.

[0053] In another aspect, the present invention provides an agent for enhancing the expression of at least one gene selected from the group consisting of KRT14, PCNA, EGFR, GRHL3, and HBEGF. In another aspect, the present invention provides use of naringenin for producing a cell activator or a cell activating composition. In another aspect, the present invention provides a method for activating cells, comprising administering naringenin to a subject. The cells to be activated are preferably skin cells. In another aspect, the present invention provides a use of naringenin for cell activation, preferably for non-therapeutic purposes, more preferably for cosmetic purposes. In another aspect, the present invention provides naringenin for cell stimulation. [Example]

[0054] The present invention will be described below with reference to examples, but the present invention is not limited to the following examples.

[0055] [Experimental Example 1] (Cell activation test) The cell-activating effect of naringenin was investigated using the following procedure. β-Eudesmol was used as a positive control compound. β-Eudesmol is a sesquiterpenoid found in the herbal medicine Atractylodes rhizome, and has been reported to have cell-activating effects by promoting the production of hyaluronic acid.

[0056] 5 × 10 cells were cultured in a 2% FBS-containing medium (FibroLife, Kurabo Industries, Ltd.). 4 A cell suspension of human normal fibroblasts (NHDF-AD) was prepared at 160 μL / mL. 160 μL of this cell suspension was seeded into a 96-well tissue culture plate. The well plate was then cultured in a CO2 incubator at 37°C for 24 hours. Next, 80 μL of a DMSO solution of naringenin (product number 5893, Sigma-Aldrich) or β-eudesmol (product number 056-05161, Fujifilm Wako Pure Chemical Industries) was prepared and added to the 96-well plate. For the negative control, 80 μL of a DMSO solution without the test substance was added. The well plate was then cultured in a CO2 incubator at 37°C for 48 hours. The number of NHDF-AD cells was then determined using Cell Counting Kit-8 (Dojindo Laboratories, Inc.) according to the instructions attached to the kit. The cell viability was calculated relative to the cell viability in the negative control, which was set at 100%.

[0057] The results are shown in Figure 1. Naringenin showed concentration-dependent cell-activating activity equivalent to that of β-eudesmol.

[0058] [Experimental Example 2] (Evaluation of expression levels of cell activation-related genes) The effect of naringenin on promoting the expression of cell activation-related genes was evaluated according to the following procedure.

[0059] The 3D epidermal model was prepared using LabCyte EPI-MODEL from Japan Tissue Engineering Co., Ltd. (J-TEC). The 3D epidermal model was pre-cultured for 24 hours in a CO2 incubator at 37°C according to the manufacturer's instructions. Naringenin was then added to the 3D epidermal model at a concentration of 0.1% (w / v). The 3D epidermal model was then incubated at 37°C in a CO2 incubator for 24 hours. Each well was washed with Dulbecco's phosphate-buffered saline (D-PBS) and then post-cultured at 37°C in a CO2 incubator for 24 hours. The cells in the wells were then treated with RNAlater (Thermo Fisher Scientific). The cells were then collected using a spatula or similar. RNA was extracted and purified from the cells using QIAzol Lysis Reagent (QIAGEN) and the spin column of the RNeasy Mini kit (QIAGEN) according to the protocol provided with the product. The purity and concentration of the purified RNA were measured using Nanodrop (registered trademark; Thermo Fisher Scientific). RNA that was not sufficiently purified was purified again using a spin column. RT-qPCR was performed using the RNA purified as described above. The primers used are shown in Table 1. In Table 1, "F" indicates the forward primer and "R" indicates the reverse primer.

[0060] [Table 1]

[0061] The results are shown in Table 2. The expression level of each gene was calculated relative to the expression level of each gene in cells cultured without the addition of naringenin, which was set at 1.00.

[0062] [Table 2]

[0063] It was confirmed that the expression of the KRT14, PCNA, EGFR, GRHL3, and BEGF genes was increased by the addition of naringenin. The increased expression of these genes is thought to contribute to the division and proliferation of basal cells (KRT14) and the turnover of epidermal cells (PCNA, EGFR, GRHL3, HBEGF), and to have a cell-activating effect.

[0064] The above results confirmed that naringenin has a cell-activating effect.

Claims

1. A cell activator containing naringenin.

2. The cell activator according to claim 1, which enhances the expression of at least one gene selected from the group consisting of KRT14, PCNA, EGFR, GRHL3, and HBEGF.

3. A cell-stimulating composition comprising naringenin and a pharmaceutically acceptable carrier.

4. The cell-stimulating composition according to claim 3, which is a cosmetic.

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