Anti-inflammatory agents and compositions for suppressing chronic inflammation

Abstract

To provide an anti-inflammatory agent and a composition for suppressing chronic inflammation that can suppress inflammation and contains naturally derived ingredients. [Solution] An anti-inflammatory agent characterized by containing naringenin; a composition for suppressing chronic inflammation characterized by containing naringenin and a pharmaceutically acceptable carrier.

Description

Technical Field

[0001] The present invention relates to an anti-inflammatory agent and a composition for suppressing chronic inflammation.

Background Art

[0002] In the skincare market, demand for naturally derived ingredients having antioxidant and anti-inflammatory effects is rising. In particular, the increase in skin troubles caused by environmental stress (ultraviolet rays, air pollution, dryness, etc.) has been recognized as a problem, and development of ingredients capable of addressing this issue, as well as cosmetics and external skin preparations using such ingredients, is in progress. Recent studies have revealed that polyphenols have antioxidant and anti-inflammatory effects and contribute to maintaining skin health, but detailed studies on the action mechanisms and effectiveness of individual components are limited.

[0003] Naringenin is a type of flavonoid, and is a polyphenol abundantly contained in citrus fruits. Regarding naringenin, antioxidant effects, anti-inflammatory effects, and anti-aging properties have been reported. For example, Patent Document 1 discloses an external skin preparation containing naringenin and 4-alkylresorcinol and / or a salt thereof as an external skin preparation for use by patients with atopic dermatitis that suppresses allergic inflammatory reactions. In addition, Non-Patent Documents 1 and 2 report that in a cellular inflammation model induced by lipopolysaccharide (LPS), naringenin can exert anti-inflammatory and antioxidant functions in LPS-induced inflammation by regulating the transcription of cytokines involved in inflammation.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Non-Patent Documents

[0005]

Non-Patent Document 1

[0006] As mentioned above, there is a growing demand for naturally derived ingredients that improve skin problems caused by everyday environmental stress, as well as cosmetics containing these ingredients. Naringenin is one such candidate substance. However, the effects and mechanism of action of naringenin on mild, non-pathological chronic inflammation remain unclear. Specifically, the invention described in Patent Document 1 is limited to patients with atopic dermatitis, and the topical skin preparation is a combination of flavonoids including naringenin and 4-alkylresosinol and / or its salts, so the effect of naringenin alone on non-pathological skin is unknown. In the inventions described in Non-Patent Documents 1 and 2, the effect of naringenin was confirmed after inducing inflammation in test cells using LPS present in the cell walls of Gram-negative bacteria, so this can be said to be a model of acute inflammation rather than chronic inflammation. In addition, Non-Patent Documents 1 and 2 use human dermal fibroblasts as cells. Dermal fibroblasts are cells that exist in the dermis, which is the layer below the epidermis, the outermost layer of the skin, while cosmetics are said to have the ability to penetrate to the epidermis, so the results of the cell tests in Non-Patent Documents 1 and 2 are not relevant from the perspective of cosmetics. Therefore, the effect of naringenin on chronic inflammation has not been clarified, and the anti-inflammatory effect of cosmetics has not been confirmed.

[0007] The present invention has been made in view of the above circumstances, and aims to provide an anti-inflammatory agent and a composition for suppressing chronic inflammation that can suppress inflammation, particularly chronic inflammation, and that contains naturally derived components. [Means for solving the problem]

[0008] In other words, the present invention provides the following invention. (1) An anti-inflammatory agent characterized by containing naringenin. (2) The anti-inflammatory agent described in (2) above, wherein the inflammation is chronic inflammation of the human epidermis. (3) The anti-inflammatory agent according to (1) or (2) above, which alters the expression of at least one gene selected from the group consisting of COX2, IL-6, TNF-α, MMP-1, and HO-1. (4) Any of the anti-inflammatory agents described in (1) to (3) above that inhibit the translocation of NF-κB protein to the nucleus. (5) A composition for suppressing chronic inflammation, characterized by containing naringenin and a pharmaceutically acceptable carrier. (6) A composition for suppressing chronic inflammation according to (5), which is a cosmetic or a topical skin preparation. (7) Use of naringenin on healthy human epidermis to suppress chronic inflammation. (8) A method for suppressing inflammation of human epidermis, characterized by administering a composition containing naringenin and a pharmaceutically acceptable carrier to healthy human epidermis. [Effects of the Invention]

[0009] The present invention provides novel anti-inflammatory agents and compositions for suppressing chronic inflammation. [Brief explanation of the drawing]

[0010] [Figure 1] This is a schematic diagram illustrating the estimated effects of naringenin on the skin. [Modes for carrying out the invention]

[0011] In this specification, gene names are represented by the human gene symbols used in the NCBI's nucleotide sequence database (GenBank®) (official symbols of the Human Genome Nomenclature Committee (HGNC)). When a particular gene name is represented by a human gene symbol, in animals other than humans, it refers to the ortholog of that gene for that animal (for example, the one identified in the aforementioned Gene database).

[0012] [Anti-inflammatory drugs] A first aspect of the present invention is an anti-inflammatory agent containing naringenin. In the anti-inflammatory agent, naringenin is contained as an active ingredient.

[0013] <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.

[0014] [ka]

[0015] The production method of naringenin is not particularly limited, and naringenin can be produced by a known method. The production method of naringenin is not particularly limited, and a known method can be used. Naringenin may be a naturally derived compound, a compound chemically synthesized using naturally derived or artificial raw materials, or a compound obtained by precision fermentation using a microorganism or the like. Examples of naturally derived naringenin include naringenin extracted and purified from plants such as citrus fruits (e.g., grapefruit, orange, etc.). Examples of naringenin obtained by precision fermentation include naringenin extracted and purified from the culture after culturing a naringenin-producing microorganism (e.g., genetically modified Escherichia coli, etc.) in the presence of an organic carbon source (e.g., glycerol, sugar, organic acid, amino acid, or biomass containing these, etc.).

[0016] <Use> An anti-inflammatory agent is a preparation having an action of suppressing an inflammatory reaction. Inflammation may be directly suppressed, or may be suppressed via an antioxidant action (reduction of oxidative stress) or the like. The anti-inflammatory agent of the present invention is preferably targeted at human skin cells. The skin cells may be cells present in the epidermis layer or cells present in the dermis layer, and it is more preferable that the anti-inflammatory agent is targeted at the epidermis layer. Examples of cells present in the epidermis layer include granular cells, spinous cells, Langerhans cells, basal cells and the like. Examples of cells present in the dermis layer include fibroblasts.

[0017] The anti-inflammatory agent of the present embodiment may be used to change the expression of at least one gene selected from the group consisting of COX2, IL-6, TNF-α, MMP-1 and HO-1. More specifically, the anti-inflammatory agent of the present embodiment may be used to suppress the expression of at least one gene selected from the group consisting of COX2, IL-6, TNF-α and MMP-1, and may be used to enhance the expression of the HO-1 gene. Furthermore, the anti-inflammatory agent of this embodiment may suppress the progression of the inflammatory response by directly or indirectly inhibiting the release and translocation of NF-κB protein present in the cytoplasm of target cells to the nucleus.

[0018] The "COX2 gene" is the gene that encodes COX2 (cyclooxygenase-2; also known as PTGS2 (prostaglandin-endoperoxide synthase 2)). Increased COX2 levels lead to excessive production of prostaglandin E2 (PGE2). Prostaglandin E2 is involved in vasodilation of the dermis and causes erythema. Therefore, suppressing COX2 gene expression is expected to have the effect of suppressing excessive inflammation, including erythema and edema, caused by UV exposure. An example of the nucleotide sequence of the human COX2 gene is the nucleotide sequence registered in the GenBank database with accession number: NM_000963. The nucleotide sequence of the COX2 gene is not limited to the aforementioned nucleotide sequence, as long as it encodes a protein that functions as COX2. The COX2 gene includes human COX2 gene nohomlogs, paralogs, and orthologs, as long as it encodes a protein that functions as COX2.

[0019] The "IL-6 gene" is the gene that codes for IL-6 (interleukin-6). Excessive production of IL-6 can cause dysregulation of the immune system, abnormalities in blood components, promotion of cancer cell proliferation and metastasis, bone destruction, and induction of inflammatory responses. Therefore, suppressing the expression of the IL-6 gene can be expected to have an anti-inflammatory effect. An example of the nucleotide sequence of the human IL-6 gene is the nucleotide sequence registered in the GenBank database with accession number: NM_000600. The nucleotide sequence of the IL-6 gene is not limited to the aforementioned nucleotide sequence, as long as it codes for a protein that functions as IL-6. The IL-6 gene includes human IL-6 gene nohomlogs, paralogs, and orthologs, as long as it codes for a protein that functions as IL-6.

[0020] The "TNF-α gene" is the gene that codes for TNF-α (tumor necrosis factor alpha). TNF-α induces the production of various cytokines and further induces cell adhesion factors present in vascular endothelial cells of the dermis, thereby increasing the vascular permeability of inflammatory cells (leukocytes) present in the blood and strengthening the inflammatory response. Therefore, suppressing the expression of the TNF-α gene is expected to reduce skin redness and suppress inflammation. An example of a nucleotide sequence of the human TNF-α gene is the nucleotide sequence registered in the GenBank database with accession number: NM_000594. The nucleotide sequence of the TNF-α gene is not limited to the aforementioned nucleotide sequence, as long as it codes for a protein that functions as TNF-α. The TNF-α gene includes human TNF-α gene nohomlogs, paralogs, and orthologs, as long as it codes for a protein that functions as TNF-α.

[0021] The "MMP-1 gene" is the gene that encodes MMP-1 (Matrix Metallopeptidase 1). MMP-1 is a proteolytic enzyme involved in the degradation of the extracellular matrix (elastin, collagen, proteoglycans) and the secretion of inflammatory cytokines. Therefore, suppressing the expression of the MMP-1 gene is expected to have anti-aging effects such as anti-wrinkle and anti-inflammatory effects. An example of the nucleotide sequence of the human MMP-1 gene is the nucleotide sequence registered in the GenBank database with accession number: NM_002421. The nucleotide sequence of the MMP-1 gene is not limited to the aforementioned nucleotide sequence, as long as it codes for a protein that functions as MMP-1. The MMP-1 gene includes human MMP-1 gene nohomlogs, paralogs, and orthologs, as long as it codes for a protein that functions as MMP-1.

[0022] The "HO-1 gene" is the gene that encodes HO-1 (Heme Oxygenase 1). HO-1 is strongly induced by various factors that induce oxidative stress, such as heat shock, heavy metals, hypoxia, inflammatory cytokines, ultraviolet radiation, H2O2, and LPS. HO-1 is an enzyme that breaks down heme and has a cytoprotective effect against oxidative stress. Therefore, increased expression of the HO-1 gene can be expected to have anti-aging effects through antioxidant and cytoprotective effects. An example of the nucleotide sequence of the human HO-1 gene is the nucleotide sequence registered in the GenBank database with accession number: NM_002133. The nucleotide sequence of the HO-1 gene is not limited to the aforementioned nucleotide sequence, as long as it codes for a protein that functions as HO-1. The HO-1 gene includes human HO-1 gene nohomlogs, paralogs, and orthologs, as long as it codes for a protein that functions as HO-1.

[0023] NF-κB is a protein that functions as a transcription factor. Under normal circumstances, NF-κB is retained in the cytoplasm and inactivated by binding to the IκB protein. However, when a cell receives some kind of stimulus, the IκB protein is degraded, and the freed NF-κB can move into the cell nucleus. Once in the nucleus, NF-κB activates the transcription of inflammation-related genes (e.g., COX-2, IL-6, TNF-α, MMP-1, etc.), thereby promoting the progression of the inflammatory response. In other words, naringenin inhibits the translocation of NF-κB to the nucleus, thereby suppressing the development of excessive and chronic inflammatory responses.

[0024] Figure 1 shows the effects of naringenin (NAR) on the skin as estimated by the inventors' studies. Environmental stress such as UV radiation and other stimuli (e.g., LPS) that occur daily lead to the degradation of IκB protein, resulting in NFκB translocation into the nucleus and activation of the NF-κB pathway. Activation of the NF-κB pathway leads to increased expression of inflammatory cytokines (COX-2, TNF-α, IL-6) and increased expression of collagen-degrading enzymes MMP-1 and MMP-3 through positive feedback by SASP factors amplified from mild inflammation. In contrast, naringenin is thought to suppress the NF-κB pathway by preventing NF-κB translocation into the nucleus, thereby preventing skin aging.

[0025] In this specification, "enhanced gene expression" means that the expression level of the target gene in cells cultured in the presence of the anti-inflammatory agent of this embodiment increases compared to the expression level of the target gene in control cells (control group) cultured in the absence of the anti-inflammatory agent of this embodiment. The expression level of the target gene in cells cultured in the presence of the anti-inflammatory agent 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.

[0026] In this specification, "suppression of gene expression" means that the expression level of the target gene in cells cultured in the presence of the anti-inflammatory agent of this embodiment is reduced compared to the expression level of the target gene in control cells (control group) cultured in the absence of the anti-inflammatory agent of this embodiment. The expression level of the target gene in cells cultured in the presence of the anti-inflammatory agent of this embodiment may be reduced 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, or 98% or more compared to the expression level of the target gene in the control group.

[0027] Changes in gene expression levels can be confirmed by known methods. One method for measuring gene expression levels is transcriptome analysis, which involves comprehensively obtaining transcripts of the target gene and measuring 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.

[0028] The anti-inflammatory agent of this embodiment may be used as is, or it may be incorporated into cosmetics, topical skin preparations, quasi-drugs, pharmaceuticals, etc., for the purpose of imparting a function to suppress inflammatory responses. It may also be incorporated into the chronic inflammation suppression composition described later.

[0029] [Composition for suppressing chronic inflammation] A second aspect of the present invention is a composition for suppressing chronic inflammation, comprising naringenin and a pharmaceutically acceptable carrier. The composition for suppressing chronic inflammation contains naringenin as an active ingredient. The composition for suppressing chronic inflammation may also contain an anti-inflammatory agent according to the first aspect.

[0030] The chronic inflammation suppression composition of this embodiment can be manufactured by compounding naringenin and, optionally, other components according to a conventional method (for example, a method described in the Japanese Pharmacopoeia).

[0031] Other components include pharmaceutically acceptable carriers. A "pharmaceutically acceptable carrier" means a carrier that does not inhibit the physiological activity of the active ingredient and does not exhibit substantial toxicity to the target of use. "Exhibiting substantial toxicity" means that the ingredient does not exhibit toxicity to the target of use at the amount normally used. Pharmaceutically acceptable carriers are not particularly limited and include oily components, humectants, 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 (whitening agents, anti-inflammatory agents, hair growth agents, blood circulation promoters, stimulants, anti-aging agents, etc.), vitamins and their derivatives, hormones, various extracts, fragrances, colorants (pigments, colorants, dyes, pigments), etc.

[0032] Oily components include higher alcohols such as cetanol, myristyl alcohol, oleyl alcohol, lauryl alcohol, cetostearyl alcohol, stearyl alcohol, arachidodecanol, behenyl alcohol, jojoba alcohol, chimyl alcohol, cerachidodecanol, batyl alcohol, hexyldecanol, isostearyl alcohol, 2-octyldodecanol, and dimergol; aralkyl alcohols and their derivatives such as benzyl alcohol; lauric acid, myristic acid, palmitic acid, stearic acid, and isostearic acid. , behenic acid, undecylenic acid, 12-hydroxystearic acid, palmitoleic acid, oleic acid, linoleic acid, erucic acid, docosahexaenoic acid, eicosapentaenoic acid, isohexadecanoic acid, anteisohenicosanic acid, long-chain branched fatty acids, dimer acids, hydrogenated dimer acids and other higher fatty acids, and their aluminum salts, calcium salts, magnesium salts, zinc salts, sodium salts, potassium salts and other metal soaps, and amine salts such as ethanolamine salts, and nitrogen-containing derivatives such as amides; liquid paraffin (mineral oil), heavy liquid ion Carbides such as soparaffins, light liquid isoparaffins, α-olefin oligomers, polyisobutenes, hydrogenated polyisobutenes, polybutenes, squalanes, olive-derived squalanes, squalenes, petrolatum, and solid paraffins; waxes such as candelilla wax, carnauba wax, rice wax, wood wax, beeswax, montan wax, ozokerite, ceresin, paraffin wax, microcrystalline wax, petrolatum, Fischer-Tropsch wax, polyethylene wax, and ethylene-propylene copolymers; coconut oil, Vegetable oils 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, peach kernel 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, hydrogenated jojoba oil, etc.; animal fats such as beef tallow, milk fat, horse fat, egg yolk oil, mink oil, turtle oil, etc.Animal waxes such as whale wax, lanolin, and orange roughy oil; lanolin compounds such as liquid lanolin, reduced lanolin, adsorbed and purified lanolin, lanolin acetate, liquid lanolin acetate, hydroxylanolin, polyoxyethylene lanolin, lanolin fatty acids, hard lanolin fatty acids, lanolin alcohol, lanolin acetate alcohol, and (cetyl lanolyl) acetate; lecithin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol Phosphatidylinositol, sphingomyelin and other sphingophospholipids, phosphatidic acid, lysolecithin and other phospholipids; phospholipid derivatives such as hydrogenated soybean phospholipid, partially hydrogenated soybean phospholipid, hydrogenated egg yolk phospholipid, partially hydrogenated egg yolk phospholipid; cholesterol, dihydrocholesterol, lanosterol, dihydrolanosterol, phytosterol, cholic acid and other sterols; 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 sarcosinate isopropyl Sterol esters such as acyl sarcosinate alkyl esters, cholesteryl 12-hydroxystearate, macadamia nut oil fatty acid cholesteryl, macadamia nut oil fatty acid phytosteryl, phytosteryl isostearate, soft lanolin fatty acid cholesteryl, hard lanolin fatty acid cholesteryl, long-chain branched fatty acid cholesteryl, long-chain α-hydroxy fatty acid cholesteryl; lipid complexes such as phospholipid-cholesterol complexes and phospholipid-phytosterol complexes;Octyldodecyl myristate, hexyldecyl myristate, octyldodecyl isostearate, cetyl palimitate, 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 Monoalcoholic carboxylic acid esters such as octyldodecyl, octyldodecyl lanolate, hexyldecyl dimethyloctanoate, octyldodecyl erucate, hydrogenated castor oil isostearate, ethyl oleate, ethyl avocado oil fatty acid, isopropyl myristate, isopropyl palmitate, octyl palmitate, isopropyl isostearate, isopropyl lanolate, triethyl citrate; oxyacid esters such as cetyl lactate, diisostearyl malate, 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 eicosanedioate behenate, glyceryl tetradecanediol / eicosanedioate, polyglyceryl-10 tetradecanediol / eicosanedioate, 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 2,4-diethyl-1,5-pentanediol dineopentanoate, propylene glycol dioleate, pentaerythrityl tetraoctanoate, hydrogenated rosin pentaerythrityl, ditrimethylolpropane triethylhexanoate, ditrimethylolpropane (isostearate / sebacate), pentaerythrityl triethylhexanoate, dipentaerythrityl (hydroxystearate / stearate / rosinate), diglyceryl diisostearate, polyglyceryl tetraisostearate, polyglyceryl-10 nonaisostearate, polyglyceryl-8 dec(erucate / isostearate / ricinoleate), diglyceryl oligoester (hexyldecanoate / sebacate), glycol distearate (ethylene glycol distearate);Diisopropyl dimer dilinoleate, diisostearyl dimer dilinoleate, di(isostearyl / phytosteryl) dimer dilinoleate, (phytosteryl / behenyl) dimer dilinoleate, (phytosteryl / isostearyl / cetyl / stearyl / behenyl) dimer dilinoleate, dimer dilinoleyl bis(phytosteryl / behenyl / isostearyl) dimer dilinoleate, dimer dilinoleyl diisostearate, hydrogenated rosin condensate of dimer dilinoleate, hydrogenated castor oil dimer dilinoleate, hydroxyalkylated Dimer acid or dimer ol derivatives such as imergerinoleyl 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, (aminoethylaminopropyl methicone / dimethicone) copolymer, dimethiconol, dimethiconol crosspolymer, silicone resin, silicone rubber, amino-modified silicones such as aminopropyl dimethicone and amodimethicone, cationic-modified silicones, polyether-modified silicones such as dimethicone copolyol, polyglycerides Silicones such as phosphorus-modified silicones, sugar-modified silicones, carboxylic acid-modified silicones, phosphate-modified silicones, sulfuric acid-modified silicones, alkyl-modified silicones, fatty acid-modified silicones, alkyl ether-modified silicones, amino acid-modified silicones, peptide-modified silicones, fluorine-modified silicones, cation-modified and polyether-modified silicones, amino-modified and polyether-modified silicones, alkyl-modified and polyether-modified silicones, and polysiloxane-oxyalkylene copolymers are preferred. Fluorine-based oils such as perfluorodecane, perfluorooctane, and perfluoropolyether are also preferred.

[0033] As humectants and texture enhancers, these include: 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, ethylene glycol-propylene glycol copolymers and other polyols and their polymers; 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 sugars and their derivatives such as raffinose, gluconic acid, glucuronic acid, β-glucan, chitin, chitosan, heparin and derivatives, pectin, arabinogalactan, dextrin, dextran, glycogen, ethyl glucoside, glucosylethyl methacrylate polymer or copolymer; hyaluronic acid, sodium hyaluronate; sodium chondroitin sulfate; mucoitin sulfate, caronin sulfate, kerato sulfate, dermatan sulfate; Tremella fuciformis extract, Tremella fuciformis polysaccharide; fucoidan; tuberose polysaccharide, etc. 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 salt and other salts; 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;Protein peptides and their derivatives such as collagen, fish-derived collagen, atelocollagen, gelatin, elastin, collagen-degraded peptides, hydrolyzed collagen, hydroxypropylammonium chloride hydrolyzed collagen, elastin-degraded peptides, keratin-degraded peptides, hydrolyzed keratin, conchiolin-degraded peptides, hydrolyzed conchiolin, silk protein-degraded peptides, hydrolyzed silk, sodium lauroyl hydrolyzed silk, soy protein-degraded peptides, wheat protein-degraded peptides, hydrolyzed wheat protein, casein-degraded peptides, acylated peptides, etc.; palmitoyl oligopeptides, palmitoyl pentapeptides, palmitoyl tetrapeptides, etc. Preferred ingredients include ceramides; silylated peptides; lactic acid bacteria culture solution, yeast extract, eggshell membrane protein, bovine submandibular gland mucin, hypotaurine, sesamin glycosides, glutathione, albumin, whey; choline chloride, phosphorylcholine; placental extract, aerlastin, collagen, witch hazel water, loofah water, chamomile extract, licorice extract, comfrey extract, silk extract, rose extract, yarrow extract, eucalyptus extract, sweet clover extract, and other animal and plant extracts; natural ceramides (types 1, 2, 3, 4, 5, 6), hydroxyceramides, pseudoceramides, sphingoglycolipids, ceramides, and ceramide-containing extracts; and other ceramides.

[0034] Preferred surfactants include anionic surfactants, nonionic surfactants, cationic surfactants, amphoteric surfactants, and polymeric surfactants. There are no particular restrictions on the HLB of the surfactant; those with a low HLB of around 1 to a high HLB of around 20 can be used, and it is also preferable to combine those with low and high HLB values. Examples of preferred surfactants include anionic surfactants such as fatty acid salts like potassium laurate and potassium myristate; alkyl sulfate esters 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-methyl amino acid salts such as sodium cocoyl methyl taurate, potassium cocoyl methyl taurate, sodium lauroyl methyl taurate, sodium myristoyl methyl taurate, sodium lauroyl methylalanine, sodium lauroyl sarcosinate, triethanolamine lauroyl sarcosinate, and sodium lauroyl glutamate methylalanine; 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 ester salts such as sodium lauroyl monoethanolamide succinate; fatty acid alkanolamide ether carboxylates; acyl lactates; polyoxyethylene fatty acid amine sulfates; fatty acid alkanolamide sulfates; fatty acid glyceride sulfates such as sodium hydrogenated coconut oil fatty acid glycerin sulfate; alkylbenzene polyoxyethylene sulfates; olefin sulfonates such as sodium α-olefin sulfonate; alkyl sulfosuccinates such as disodium lauryl sulfosuccinate and sodium dioctyl sulfosuccinate; alkyl ether sulfosuccinates such as disodium laureth sulfosuccinate, monolauroyl monoethanolamide polyoxyethylene sulfosuccinate sodium, and sodium lauryl polypropylene glycol sulfosuccinate sodium;Alkylbenzenesulfonates such as sodium tetradecylbenzenesulfonate and triethanolamine tetradecylbenzenesulfonate; alkylnaphthalene sulfonates; alkanesulfonates; α-sulfo fatty acid methyl ester salts; acyl isethionates; alkyl glycidyl ether sulfonates; alkyl sulfoacetates; alkyl ether phosphate salts such as sodium laureth phosphate, sodium dilaureth phosphate, sodium trilaureth phosphate, and sodium monooleth phosphate; alkyl phosphate 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 silicones, phosphate-modified silicones, and sulfate-modified silicones; nonionic surfactants include laureth (polyoxyethylene lauryl ether) and ceteth (polyoxyethylene lauryl ether). Polyoxyethylene alkyl ethers of 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 alkylphenyl ethers; castor oil and hydrogenated castor oil derivatives such as polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil monoisostearate, polyoxyethylene hydrogenated castor oil triisostearate, polyoxyethylene hydrogenated castor oil monopyroglutamic acid monoisostearate diester, and polyoxyethylene hydrogenated castor oil maleic acid; polyoxyethylene phytosterol; polyoxyethylene cholesterol; polyoxyethylene cholestanol; polyoxyethylene lanolin; 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, polyoxyethylene / polyoxypropylene glycerin ether; polyoxyethylene / polyoxypropylene glycol; (poly) such as PPG-9 diglyceryl. ) Glycerin polyoxypropylene glycol; glyceryl stearate, glyceryl isostearate, glyceryl palmitate, glyceryl myristate, glyceryl oleate, coconut oil fatty acid glyceryl, monocottonseed oil fatty acid glycerin, monoerucate glycerin, sesquioleate glycerin, α,α'-oleate pyroglutamate glycerin, monostearate glycerin malic acid and other glycerin fatty acid partial esters; polyglyceryl-2, 3, 4, 5, 6, 8 stearate , same 10, polyglyceryl-6 distearate, same 10, polyglyceryl-2 tristearate, polyglyceryl-10 decaisostearate, polyglyceryl-2 isostearate, same 3, same 4, same 5, same 6, same 8, same 10, polyglyceryl-2 diisostearate (diglyceryl diisostearate), same 3, same 10, polyglyceryl-2 triisostearate, polyglyceryl-2 tetraisostearate, polyglyceryl-10 decaisostearate, polyglyceryl-2 oleate, same 3, Polyglycerin fatty acid esters such as Polyglyceryl-6 dioleate, Polyglyceryl-2 trioleate, Polyglyceryl-10 decaoleate; Ethylene glycol monofatty acid esters such as Ethylene glycol monostearate; Propylene glycol monofatty acid esters such as Propylene glycol monostearate; Pentaerythritol partial fatty acid ester; Sorbitol partial fatty acid ester; Maltitol partial fatty acid ester; Maltitol ether;Sorbitan fatty acid esters such as sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, sorbitan trioleate, sorbitan penta-2-ethylhexyl diglycerol sorbitan, sorbitan tetra-2-ethylhexyl diglycerol sorbitan; sugar derivative partial esters such as sucrose fatty acid esters, methyl glucoside fatty acid esters, and trehalose undecylenate; alkyl glucosides such as caprylyl glucoside; alkyl polyglycerides Coside; lanolin alcohol; reduced lanolin; polyoxyethylene fatty acid mono and diesters such as polyoxyethylene distearate, polyethylene glycol diisostearate, polyoxyethylene monooleate, polyoxyethylene dioleate; polyoxyethylene propylene glycol fatty acid esters; polyoxyethylene glycerin fats such as polyoxyethylene monooleate, polyoxyethylene glycerin monoisostearate, polyoxyethylene glycerin triisostearate, and other polyoxyethylene monooleates. 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, chymyl alcohol, cerakyl alcohol, and batyl alcohol; polyhydric alcohol alkyl ethers; polyoxyethylene alkylamines; tetrapolyoxyethylene-tetrapolyoxypropylene-ethylenediamine condensates; natural surfactants such as saponins 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); lauramine oxide nonionic silicone surfactants such as: alkyldimethylamine oxides such as cocamine oxide, stearamine oxide, and behenamine oxide; alkylethoxydimethylamine oxide; polyoxyethylene alkyl mercaptan; polyether-modified silicones such as dimethicone copolyol, polysiloxane-oxyalkylene copolymers, polyglycerin-modified silicones, sugar-modified silicones, etc.; cationic surfactants such as behentrimonium chloride, steartrimonium chloride, cetrimonium chloride, lauryltrimonium Alkyltrimethylammonium chlorides such as nium chloride; alkyltrimethylammonium bromides such as stearyltrimonium bromide; dialkyldimethylammonium chlorides such as distearyldimonium chloride and dicocodimonium chloride; fatty acid amide amines and their salts such as stearamidopropyldimethylamine and stearamidoethyldiethylamine; alkyl etheramines and their salts or quaternary salts such as stearoxypropyldimethylamine; fatty acid amide-type quaternary ammonium salts such as ethyl sulfate long-chain branched fatty acid (12-31) aminopropylethyldimethylammonium and ethyl sulfate lanolin fatty acid aminopropylethyldimethylammonium; polyoxyethylene alkylamines and their salts or quaternary salts; alkylamine salts; fatty acid amide guanidium salts; alkyl etheramine mononium salts; alkyl trialkylene glycol ammonium salts; benzalkonium salts; benzethonium salts; pyridinium salts such as cetylpyridinium chloride; imidazolinium salts; alkylisoquinolinium salts; dialkylmolyphonium salts; polyamine fatty acid derivatives;Silicone-based cationic surfactants such as aminopropyl dimethicone and amodimethicone (amino-modified silicones), cationic-modified silicones, cationic and polyether-modified silicones, amino-modified and polyether-modified silicones, etc.; amphoteric surfactants such as N-alkyl-N,N-dimethylamino acid betaines such as lauryl betaine (lauryldimethylaminoacetic acid betaine); fatty acid amide alkyl-N,N-dimethylamino acid betaines such as cocamidopropyl betaine and lauramidopropyl betaine; imidazoline-type betaines such as sodium cocoamphoacetate and sodium lauroamphoacetate; alkyl sulfobetaines such as alkyldimethyl taurine; sulfate-type betaines such as alkyldimethylaminoethanol sulfate; phosphate-type betaines such as alkyldimethylaminoethanol phosphate; sphingolin lipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and sphingomyelin; Phospholipids such as lysolecithin, hydrogenated soybean phospholipid, partially hydrogenated soybean phospholipid, hydrogenated egg yolk phospholipid, partially hydrogenated egg yolk phospholipid, and hydroxylated lecithin; silicone-based amphoteric surfactants; and polymeric surfactants such as polyvinyl alcohol, sodium alginate, starch derivatives, tragacanth gum, acrylic acid / alkyl methacrylate copolymer, and 2-methachloroyloxyethyl phosphorylcholine / stearyl methacrylate copolymer; and various silicone-based surfactants are preferred.

[0035] Various polymers, thickeners, and gelling agents include guar gum, locust bean gum, queen seed gum, carrageenan, galactan, gum arabic, tara gum, tamarind, fercerelan, karaya gum, okra gum, tragacanth gum, pectin, pectic acid and its salts, alginic acid and its salts, mannan; starches from rice, corn, potato, wheat, etc.; xanthan gum, dextran, succinoglucan, curdlan, hyaluronic acid and its salts, xanthan gum, pullulan, gellan gum, chitin, chitosa Cellulose, agar, cassia seed extract, chondroitin sulfate, casein, collagen, gelatin, albumin; methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose and its sodium salts, methylhydroxypropylcellulose, sodium cellulose sulfate, dialkyldimethylammonium sulfate, crystalline cellulose, cellulose powder, and other cellulose and its derivatives; soluble starch, carboxymethyl starch, methylhydroxypropyl starch, methyl starch, and other derivatives Starch derivatives such as corn starch aluminum octenyl succinate, hydroxypropyltrimonium chloride, and octenyl succinate; alginic acid derivatives such as sodium alginate and propylene glycol alginate; polyvinylpyridone (PVP), polyvinyl alcohol (PVA), vinylpyridone-vinyl alcohol copolymer, and polyvinyl methyl ether; polyethylene glycol, polypropylene glycol, and 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, and (alkyl acrylate / diacetone acrylamide) copolymer AMP; partially saponified polyvinyl acetate and maleic acid copolymer; vinylpyrrolidone-dialkylaminoalkyl methacrylate copolymer; acrylic resin alkanolamine; polyesters and water-dispersible polyesters.Polyacrylamide; polyacrylic acid ester copolymers such as ethyl polyacrylate, carboxyvinyl polymers, salts such as polyacrylic acid and its 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 methacrylamide copolymers, acrylic acid / methyl acrylate / methacrylamidopropyltrimethylammonium chloride copolymers such as polyquaternium-47, choline methacrylate ester polymers; cationized oligosaccharides, cationized dextran, cationized guar hydroxypropyltrimonium chloride, etc. Polysaccharides; polyethyleneimines; cationic polymers; copolymers of 2-methacryloyloxyethyl phosphorylcholine polymers such as polyquaternium-51 and butyl methacrylate copolymers; polymer emulsions such as acrylic resin emulsions, ethyl polyacrylate emulsions, polyacrylic alkyl ester emulsions, polyvinyl acetate resin emulsions, natural rubber latex, and synthetic latex; nitrocellulose; polyurethanes and various copolymers; various silicones; various silicone-based copolymers such as acrylic-silicone graft copolymers; various fluorine-based polymers; 12-hydroxystearic acid and its salts; dextrin fatty acid esters such as dextrin palmitate and dextrin myristate; anhydrous silicic acid, fuzzy silica (ultrafine particle anhydrous silicic acid), magnesium aluminum silicate, magnesium sodium silicate, metal soaps, dialkyl phosphate metal salts, bentonite, hectorite, organically modified clay minerals, sucrose fatty acid esters, and fructooligosaccharide fatty acid esters are among the preferred materials.

[0036] Preferred antioxidants include alpha-lipoic acid, salts of alpha-lipoic acid, and derivatives of alpha-lipoic acid; 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.

[0037] As preservatives and antibacterial agents, 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; acid ammonium compounds Preferred materials include dihydrogen ammonium compounds, quaternary ammonium salts; trichlorocarbanides, zinc pyrithione, benzalkonium chloride, benzethonium chloride, sorbic acid, chlorhexidine, chlorhexidine gluconate, halocarban, hexachlorophene, hinokitiol; phenols, isopropylphenol, cresol, thymol, parachlorophenol, phenylphenol, sodium phenylphenol, and other phenols; phenylethyl alcohol, photosensitizers, antibacterial zeolites, and silver ions.

[0038] Preferred chelating agents 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 their 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.

[0039] Preferred pH adjusters and acids / alkalis 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.

[0040] Powders include mica, talc, kaolin, sericite, montmorillonite, kaolinite, mica, muscovite, phlogopite, synthetic mica, red mica, biotite, vermiculite, magnesium carbonate, calcium carbonate, aluminum silicate, barium silicate, calcium silicate, magnesium silicate, strontium silicate, tungstate metal salts, 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 dioxide, fine and ultrafine titanium dioxide, zinc oxide, fine and ultrafine zinc oxide, alumina, silica, fuzzy silica (ultrafine anhydrous silicic acid), and titanium mica. Preferred materials include inorganic powders of various sizes and shapes such as fish scale foil, boron nitride, photochromic pigments, synthetic fluorphlogopite, fine particle composite powders, gold, aluminum, and inorganic powders that have been hydrophobized or hydrophilized by treating them with various surface treatment agents such as hydrogen silicone, cyclic hydrogen silicone, or other silanes or titanium coupling agents; 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 laminated powder, polyethylene terephthalate-aluminum-epoxy laminated powder, urethane powder, silicone powder, Teflon® powder, and other organic powders and surface-treated powders, as well as organic-inorganic composite powders.Preferred 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 1Na, 2Na, and 3Na phosphates, potassium phosphates, calcium phosphates, and magnesium phosphates.

[0041] UV absorbers include benzoic acid-based UV absorbers such as para-aminobenzoic acid, para-aminobenzoic acid monoglycerol ester, N,N-dipropoxypara-aminobenzoate ethyl ester, N,N-diethoxypara-aminobenzoate ethyl ester, N,N-dimethylpara-aminobenzoate ethyl ester, N,N-dimethylpara-aminobenzoate butyl ester, and N,N-dimethylpara-aminobenzoate ethyl ester; anthranilic acid-based UV absorbers such as homomenthyl-N-acetylanthranilate; salicylic acid-based UV absorbers such as salicylic acid and its sodium salt, amyl salicylate, menthyl salicylate, homomenthyl salicylate, octyl salicylate, phenyl salicylate, benzyl salicylate, and p-isopropanolphenyl salicylate; and 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-methoxy cinnamate, isopropyl-p-methoxy cinnamate, isoamyl-p-methoxy cinnamate, 2-ethylhexyl-p-methoxy cinnamate (octyl paramethoxycinnamate), 2-ethoxyethyl-p-methoxy cinnamate (cinoxate), cyclohexyl-p-methoxy cinnamate, ethyl-α-cyano-β-phenyl cinnamate, 2-ethylhexyl-α-cyano-β-phenyl cinnamate (octocrine), glyceryl mono-2-ethylhexanoyl-diparamethoxy cinnamate, 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'-phenylbenzophenone-2-carboxylate, 2-hydroxy-4-n-octoxybenzophenone, 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'-hydro Xy-5'-t-octylphenyl)benzotriazole; 2-(2'-hydroxy-5'-methylphenylbenzotriazole; dibenzarazine; dianisioylmethane; 5-(3,3-dimethyl-2-norbornylidene)-3-pentan-2-one; dibenzoylmethane derivatives such as 4-t-butyl methoxydibenzoylmethane; octyltriazone; urocanic acid derivatives such as urocanic acid and ethyl urocanic acid; 2-(2'-hydroxy-5'-methylphenyl)benzotriazole; Preferred materials include benzotriazole (nyl), 1-(3,4-dimethoxyphenyl)-4,4-dimethyl-1,3-pentanedione, 2-ethylhexyl dimethoxybenzylidene dioxoimidazolidinepropionate, and other hydantoin derivatives, phenylbenzimidazol sulfonic acid, terephthalylidene dicamphor sulfonic acid, drometrizole trisiloxane, methyl anthranilate, rutin and its derivatives, and oryzanol and its derivatives.

[0042] Preferred whitening agents include ascorbic acid, ascorbic acid phosphate salts such as sodium ascorbic acid phosphate and magnesium ascorbic acid phosphate, ascorbic acid fatty acid esters such as tetraisopalmitic ascorbic acid, alkyl ascorbic acid ethers such as ethyl ascorbic acid, ascorbic acid glucosides such as ascorbic acid-2-glucoside and their fatty acid esters, ascorbic acid derivatives such as ascorbic acid sulfate and tocopheryl ascorbyl phosphate; kojic acid, ellagic acid, tranexamic acid and its derivatives, ferulic acid and its derivatives, placenta extract, glutathione, oryzanol, butylresorcinol, oil-soluble chamomile extract, oil-soluble licorice extract, willow extract, saxifrage extract, and other plant extracts.

[0043] Preferred anti-inflammatory agents include glycyrrhizic 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.

[0044] Preferred 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, gingerol, ichthammol, tannic acid, borneol, cyclandelate, cinnarizine, trazoline, acetylcholine, verapamil, cepharanthine, γ-oryzanol, cepharanthine, vitamin E and derivatives such as tocopherol nicotinate and tocopherol acetate; γ-oryzanol, nicotinic acid and derivatives such as nicotinamide, benzyl nicotinate, inositol hexanicotinate, and nicotinic alcohol; allantoin, photosensitizer 301, photosensitizer 401, capronium chloride, pentadecanoic acid monoglyceride, flavanonol derivatives, stigmasterol or stigmamanol and its glycosides; and minoxidil.

[0045] Other medicinal agents such as anti-wrinkle agents, anti-aging agents, firming agents, cooling agents, warming agents, wound healing promoters, irritation relievers, analgesics, and cell activators include retinols, retinoic acids, retinoic acid tocopheryl; lactic acid, glycolic acid, gluconic acid, fruit acids, salicylic acid and its glycosides and esters and their derivatives; hydroxycapric acid, long-chain α-hydroxy fatty acids, long-chain α-hydroxy fatty acid cholesteryl and other α- or β-hydroxy acids and their derivatives; 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 materials include antioxidants and free radical scavengers; catechins; flavonoids such as quercetin; isoflavones; gallic acid and ester sugar derivatives; polyphenols such as tannins, sesamin, protoanthocyanidins, chlorogenic acid, and apple polyphenols; rutin and glycoside derivatives; hesperidin and glycoside derivatives; lignan glycosides; licorice extract-related substances such as glabridin, glabrene, liquiritin, and isoliquiritin; lactoferrin; 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 with cyclodextrins.

[0046] Examples of antipruritic agents include diphenhydramine hydrochloride, chlorpheniramine maleate, camphor, and substance-P inhibitors. Examples of exfoliating and dissolving agents include salicylic acid, sulfur, resorcinol, selenium sulfide, and pyridoxine. Examples of antiperspirants include aluminum chlorohydrate, aluminum chloride, zinc oxide, and zinc paraphenolsulfonate. Examples of cooling agents include menthol and methyl salicylate. Examples of astringent agents include citric acid, tartaric acid, lactic acid, potassium aluminum sulfate, and tannic acid. Examples of enzymes include superoxide dismutase, catalase, lysozyme chloride, lipase, papain, pancreatin, and protease. Preferred nucleic acids include ribonucleic acid and its salts, deoxyribonucleic acid and its salts, and adenosine triphosphate disodium.

[0047] Vitamins and their derivatives include vitamin A compounds such as retinol, retinyl acetate, and retinyl palmitate; vitamin B compounds such as thiamine hydrochloride, thiamine sulfate, riboflavin, riboflavin acetate, pyridoxine hydrochloride, pyridoxine dioctanoate, pyridoxine dipalmitate, flavin adenine dinucleotide, cyanocobalamin, folic acid compounds, nicotinic acid compounds such as nicotinamide and benzyl nicotinate, and choline compounds; vitamin C compounds such as ascorbic acid and its sodium salts; vitamin D; vitamin E compounds such as α, β, γ, and δ-tocopherols; other vitamins such as pantothenic acid and biotin; and ascorbic acid phosphate sodium salt and ascorbic acid phosphate magnesium salt. Preferred materials include ascorbic acid phosphate salts, ascorbic acid fatty acid esters such as tetraisopalmitic ascorbate, ascorbyl stearate, ascorbyl palmitate, and ascorbyl dipalmitate, alkyl ascorbic acid ethers such as ethyl ascorbate, ascorbic acid glucosides such as ascorbic acid-2-glucoside and their fatty acid esters, ascorbic acid derivatives such as tocopheryl ascorbyl phosphate; vitamin derivatives such as tocopherol nicotinate, tocopherol acetate, tocopherol linoleate, tocopherol ferulate, and tocopherol phosphate esters, tocotrienols, and various other vitamin derivatives.

[0048] Preferred hormones include estradiol, estrone, ethinylestradiol, cortisone, hydrocortisone, and prednisone.

[0049] Various extracts from plants, animals, and microorganisms include iris extract, angelica extract, Thujopsis dolabrata extract, asparagus extract, avocado extract, Hydrangea macrophylla extract, almond extract, Althaea extract, Arnica extract, apricot extract, apricot kernel extract, Ginkgo biloba extract, Inca extract, fennel extract, turmeric extract, oolong tea extract, bearberry extract, rosehip extract, Echinacea leaf extract, Enmeisou extract, Scutellaria baicalensis extract, Phellodendron amurense extract, Coptis japonica extract, barley extract, Panax ginseng extract, St. John's wort extract, and Lamium album. Grass extract, Ononis extract, Nasturtium officinale extract, Orange extract, Dried seawater, Seaweed extract, Persimmon leaf extract, Arctium moniliforme extract, Hydrolyzed elastin, Hydrolyzed wheat powder, Hydrolyzed silk, Pueraria lobata extract, Chamomile extract, Oil-soluble chamomile extract, Carrot extract, Artemisia capillaris extract, Oat extract, Chloranthus erythrosora extract, Licorice extract, Oil-soluble licorice extract, Kiwi extract, Kelpodium extract, Wood ear mushroom extract, Cinchona extract, Cucumber extract, Paulownia leaf extract, Guanosine, Guava extract, Sophora flavescens extract, Gardenia extract, Sasa veitchii 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 thunbergii extract, black tea extract, yeast extract, Magnolia bark extract, coffee extract, burdock extract, rice extract, rice fermentation extract, rice bran fermentation extract, rice germ oil, comfrey extract, collagen, lingonberry extract, Asarum sieboldii extract, Bupleurum chinense extract, umbilical cord extract, saffron extract, sage extract, soapwort extract, bamboo extract, hawthorn extract, sunflower extract Sodium, Japanese pepper extract, shiitake mushroom extract, rehmannia extract, lithospermum extract, perilla extract, linden extract, meadowsweet extract, jatoba extract, peony extract, ginger extract, calamus root extract, birch extract, white fungus extract, horsetail extract, stevia extract, stevia ferment, iris extract, ivy extract, hawthorn extract, elderflower extract, yarrow extract, peppermint extract, sage extract, mallow extract, chuanxiong extract, swertia japonica extract, mulberry bark extract, rhubarb extract,Soybean extract, jujube extract, thyme extract, dandelion extract, lichen extract, tea extract, clove extract, cogongrass extract, citrus peel 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, Ophiopogon extract, lotus extract, parsley extract, birch extract, honey, witch hazel extract, parietaria extract, Isodon japonicus extract, bisabolol, cypress extract, bifidobacteria extract, loquat extract, coltsfoot extract, butterbur extract, Poria cocos extract, butcher's broom extract, grape extract Examples of extracts include grape seed extract, propolis, loofah extract, safflower extract, peppermint extract, linden extract, peony extract, hop extract, cypress extract, pine extract, horse chestnut extract, skunk cabbage extract, soapberry extract, lemon balm extract, seaweed 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, reishi mushroom extract, lettuce extract, lemon extract, forsythia extract, astragalus extract, rose extract, rosemary extract, Roman chamomile extract, royal jelly extract, and burnet extract.

[0050] The fragrance ingredients include acetylcedrene, amyl cinnamaldehyde, allyl amyl glycolate, β-ionone, iso-esuper, isobutylquinoline, iris oil, ylone, indole, ylang-ylang oil, undecanal, undecenal, γ-undecalactone, estragol, eugenol, oakmoss, opoponax resinoid, orange oil, eugenol, aurantiol, galacsolid, carvacrol, L-carbone, camphor, canone, carrot seed oil, clove oil, methyl cinnamate, geraniol, geranyl nitrile, isobornyl acetate, geranyl acetate, dimethylbenzylcarbinyl acetate, styraryl acetate, cedyl acetate, terepinel acetate, and pt-butylcyclohexyl acetate. Lu, vetiveryl acetate, benzyl acetate, linalyl acetate, isopentyl salicylate, benzyl salicylate, sandalwood oil, santalol, cyclamenaldehyde, cyclopentadecanol, 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, γ-terpinene, tripral, nerol, nonanal, 2,6-Nonadienol, Nonalactone, Patchouli Alcohol, Vanilla Absolute, Vanillin, Basil Oil, Patchouli Oil, Hydroxycitronellal, α-Pinene, Piperitone, Phenethyl Alcohol, Phenylacetaldehyde, Petitgrain Oil, Hexyl Cinnamaldehyde, cis-3-Hexenol, Peruvian Balsam, Vetiver Oil, Vetiverol, Peppermint Oil, Pepper Oil, Heliotropin, Bergamot Oil, Benzyl Benzoate Preferred examples include synthetic and natural fragrances such as benzoate, borneol, myrrhizinoid, musk ketone, methylnonylacetaldehyde, γ-methylionone, menthol, L-menthol, L-menthone, eucalyptus oil, β-ionone, lime oil, lavender oil, D-limonene, linalool, liral, lilial, lemon oil, rose absolute, rose oxide, rose oil, rosemary oil, various essential oils, and various blended fragrances.

[0051] As pigments, colorants, dyes, and dyes, they 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 γ-iron oxide; inorganic yellow pigments such as yellow iron oxide and ochre; inorganic black pigments such as black iron oxide and lower 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 Prussian 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; metal powder pigments such as aluminum powder, copper powder, and gold; surface-treated inorganic and metal powder pigments; Red 201, Red 202, Red 204, Red 205, Red 220, Red 226, Red 228, Red 405, Orange 203, Orange 204, Yellow 205, Yellow 401, Blue 404, Red 3, Red 104, Red 106, Red 22 Organic pigments such as zirconium, barium, or aluminum lake, including No. 7, Red No. 230, Red No. 401, Red No. 505, Orange No. 205, Yellow No. 4, Yellow No. 5, Yellow No. 202, Yellow No. 203, Green No. 3, Blue No. 1, etc.; surface-treated organic pigments; anthraquinones such as astaxanthin and alizarin, anthocyanidins, β-carotene, catenal, capsanthin, chalcone, calsamine, quercetin, crocin, chlorophyll, curcumin, cochineal, shikonin, and other naphthoquinones, bixy Natural pigments and dyes such as flavonoids, betacyanidin, henna, hemoglobin, lycopene, riboflavin, and rutin; oxidative 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 their salts; auto-oxidative dyes such as indoline; and dihydroxyacetone are preferred.

[0052] Other ingredients may include those listed in the Cosmetic Ingredient Standards, Cosmetic Ingredient Formulation 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 Additives Standards, and the Food Additives Compendium, as well as known cosmetic ingredients and pharmaceutical ingredients. Such ingredients can be included in the chronic inflammation suppression composition of this embodiment to the extent that a naringenin chronic inflammation suppression composition can be obtained.

[0053] The chronic inflammation suppression composition of this embodiment can contain an effective amount of naringenin. "Effective amount" means the amount of naringenin that is effective in exerting the cell-activating effect of naringenin. The effective amount may vary depending on the age, sex, and weight of the target user. In the chronic inflammation suppression 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, 0.01 to 0.1% by mass, etc., as the naringenin content in the chronic inflammation suppression composition.

[0054] The dosage form of the chronic inflammation suppression composition of this embodiment is not particularly limited. Examples of dosage forms of the chronic inflammation suppression composition of this embodiment include ampoules, capsules, pills, tablets, powders, granules, solids, liquids, gels, bubbles, emulsions, sheets, mists, sprays, etc.

[0055] The chronic inflammation suppression composition of this embodiment may be a pharmaceutical product, a quasi-drug, or a cosmetic. Preferably, the chronic inflammation suppression composition of this embodiment is a topical skin preparation. Preferably, the chronic inflammation suppression composition of this embodiment is a cosmetic, and more preferably a skin cosmetic.

[0056] When the chronic inflammation-suppressing composition of this embodiment is a cosmetic, examples include basic cosmetics such as lotions, emulsions, creams, ointments, oils, and packs; skin cleansing products such as facial cleansers and body washes; massage cosmetics such as massage agents; cleansing cosmetics such as cleansing agents; hair removal cosmetics such as depilatory agents and hair removal agents; shaving cosmetics such as shaving products, aftershave lotions, pre-shave lotions, and shaving creams; makeup cosmetics such as foundations, lipsticks, blushes, eyeshadows, eyeliners, and mascaras; and other topical cosmetics such as perfumes, nail care products, nail enamels, nail enamel removers, poultices, plasters, tapes, sheets, patches, and aerosols. The chronic inflammation-suppressing composition of this embodiment may also be a preparation for the scalp and / or hair. Examples of preparations for the scalp and / or hair include shampoos, conditioners, hair treatments, pre-hair treatments, permanent wave solutions, hair dyes, hair styling products, hair tonics, hair growth and nourishing products, scalp poultices, scalp plasters, scalp tapes, scalp sheets, scalp patches, hair or scalp aerosols, etc. The chronic inflammation-suppressing composition of this embodiment may also be a bath additive used by adding it to bathwater. The chronic inflammation-suppressing composition of this embodiment can also be used in body odor prevention agents, deodorants, antiperspirants, sanitary products, sanitary cotton, wet wipes, toothpastes, mouth fresheners, mouthwashes, dishwashing detergents, etc.

[0057] The chronic inflammation suppression composition of this embodiment has an anti-inflammatory effect by containing naringenin as an active ingredient. The chronic inflammation suppression composition of this embodiment contains naringenin as an active ingredient and has the effect of altering the expression of at least one gene selected from the group consisting of COX2, IL-6, TNF-α, MMP-1, and HO-1. More specifically, the chronic inflammation suppression composition of this embodiment contains naringenin as an active ingredient and has the effect of suppressing the expression of at least one gene selected from the group consisting of COX2, IL-6, TNF-α, and MMP-1, and has the effect of enhancing the expression of the HO-1 gene. Furthermore, the chronic inflammation suppression composition of this embodiment contains naringenin as an active ingredient, and has the effect of directly or indirectly inhibiting the release and translocation of NF-κB protein present in the cytoplasm of target cells to the nucleus. Because the chronic inflammation-suppressing composition of this embodiment has the above-mentioned effects (changes in gene expression, inhibition of NF-κB nuclear translocation), it can be used to improve dry skin, rough skin, acne, etc., promote wound healing, and provide anti-aging benefits for the skin by suppressing and improving chronic inflammation.

[0058] In another aspect, the present invention provides an inhibitor of expression of at least one gene selected from the group consisting of COX2, IL-6, TNF-α, MMP-1, and HO-1, which contains naringenin. The present invention also provides an enhancer of expression of the HO-1 gene, which contains naringenin. In another embodiment, the present invention provides the use of naringenin for producing an anti-inflammatory agent or a composition for suppressing chronic inflammation. In another embodiment, the present invention provides the use of naringenin to suppress chronic inflammation. Such use is preferably non-therapeutic, more preferably on healthy human epidermis, and even more preferably on human epidermis for cosmetic purposes. In another embodiment, the present invention provides a method for suppressing inflammation, comprising administering a composition containing naringenin and a pharmaceutically acceptable carrier to a subject. The method is preferably a non-therapeutic method, more preferably the subject is healthy human epidermis, and even more preferably the subject is human epidermis used for cosmetic purposes. In another embodiment, the present invention provides naringenin for improving skin function. The skin function includes at least one selected from the group consisting of skin moisturizing function, barrier function, skin antioxidant function, skin wound healing function, and skin anti-aging function. [Examples]

[0059] The present invention will be described below with reference to examples, but the present invention is not limited to the following examples.

[0060] (Experimental Example 1: Evaluation of Inflammation-Related Gene Expression Levels 1) The effects of naringenin on the expression levels of inflammation-related genes were evaluated using the following procedure.

[0061] The effect of naringenin on the expression levels of inflammation-related genes was evaluated using the following procedure. A human normal epidermis three-dimensional culture model (LabCyte EPI-MODEL, manufactured by Japan Tissue Engineering Co., Ltd.) was pre-cultured for 24 hours in a CO2 incubator at 37°C according to the instructions provided with the product. Next, naringenin (manufactured by Sigma-Aldrich) was dissolved in DMSO and water to a final naringenin concentration of 0.1% (w / v), which was added to the epidermal three-dimensional culture model. After incubation at 37°C for 24 hours, the cells were washed with D-PBS and incubated again at 37°C for 24 hours. Subsequently, the cells were treated with RNAlater, harvested using a spatula, and RNA was extracted and purified using QIAzol Lysis Reagent and the RNeasy Mini kit. After measuring the purity and concentration of RNA using Nanodrop, gene expression was analyzed using a gene expression microarray ("GeneChip" (registered trademark), Thermo Fisher Scientific) with the specified purity and concentration of extracted RNA as a sample. Genes whose expression levels were significantly altered in cells cultured in the presence of naringenin were extracted compared to expression in control cells without naringenin. Expression levels were calculated relative to the expression level of each gene in control cells, which was set to 1.00. The results are shown in the table below.

[0062] [Table 1]

[0063] The results above confirm that the expression of each gene related to inflammation is suppressed by the addition of naringenin. It is thought that suppressing the expression of inflammation-related genes suppresses the weak chronic inflammatory response that normally occurs in epidermal cells, thereby maintaining skin health.

[0064] (Experimental Example 2: Evaluation of Inflammation-Related Gene Expression Levels 2) The effects of naringenin on the expression levels of inflammation-related genes were evaluated using the following procedure.

[0065] Using a medium containing 10% FBS (DMEM, Kurabo Industries Ltd.), 3 × 10 5 A cell suspension of human normal fibroblasts (NHDF-NB) was prepared to a concentration of cells / mL. This cell suspension was seeded in 1000 μL portions into 12-well tissue culture plates. Next, the well plate was cultured in a CO2 incubator at 37°C for 24 hours. Next, a DMSO solution containing naringenin (NAR; Sigma-Aldrich) was prepared and added to the 12-well plates in 1 μL increments to achieve a final concentration of 5 ppm or 20 ppm. For control cells, 1 μL of DMSO solution without naringenin was added. To confirm changes in the expression of inflammation-related genes during inflammation, lipopolysaccharide (LPS; Sigma-Aldrich "Lipopolysaccharides from Escherichia coli O127:B8" (trade name)) was added to some cells at a final concentration of 1 μg / mL as an anti-inflammatory agent. Next, the cells were cultured in a CO2 incubator at 37°C for 6 hours, then treated with RNAlater. The cells were collected using a spatula, and RNA was extracted and purified using QIAzol Lysis Reagent and RNeasy Mini kit. Only the HO-1 measured cells were cultured at 37°C for 24 hours before RNA extraction and purification. After measuring the purity and concentration of RNA using Nanodrop, the expression levels of each gene were confirmed by RT-qPCR using the extracted RNA with the specified purity and concentration as a sample. Table 4 shows the primers used, and Tables 5 and 6 show the expression levels of each gene. "F" indicates a forward primer, and "R" indicates a reverse primer. Expression levels were calculated relative to the expression level of each gene in control cells, which was set to 1.00. Table 5 shows the results without LPS addition, while Table 6 shows the results when cells with only LPS added were used as control cells, and cells with both LPS and naringenin added were used as test cells.

[0066] [Table 2]

[0067] [Table 3]

[0068] [Table 4]

[0069] The results above confirm that the expression of each inflammation-related gene is altered by the addition of naringenin. Furthermore, it was suggested that suppressing the expression of each inflammation-related gene suppresses not only acute inflammation induced by LPS, etc., but also the mild chronic inflammation that normally occurs in fibroblasts. It is thought that by suppressing the expression of inflammation-related genes, chronic inflammatory responses in fibroblasts and acute inflammatory responses caused by allergens are suppressed, thereby maintaining healthy skin.

[0070] (Experimental Example 3: Evaluation of nuclear translocation of NF-κB) The following procedure was used to evaluate the effects of naringenin on inflammatory responses via NF-κB nuclear translocation.

[0071] Using a medium containing 10% FBS (DMEM, Kurabo Industries Ltd.), 3 × 10 5A cell suspension of human normal fibroblasts (NHDF-NB) was prepared to a concentration of cells / mL. This cell suspension was seeded into 35 mm tissue culture dishes and then cultured in a CO2 incubator at 37°C for 48 hours. Next, a DMSO solution containing naringenin (NAR; manufactured by Sigma-Aldrich) was prepared, and the culture medium was prepared so that the final concentration of naringenin was 5 ppm or 20 ppm. The culture medium was then changed using this medium. In some cells, the culture medium was 4 J / cm³ after the medium change. 2 UVA light was then applied. Four hours after changing the culture medium, fibroblasts were fixed with 4% paraformaldehyde (PFA) and permeabilized and blocked with PBS containing 1% bovine serum albumin (BSA) and 0.1% Triton X-100 (Sigma-Aldrich). Next, they were incubated at 4°C for 18 hours with NF-κB antibody (Cell Signaling Technology, "NFκB p65(D14E12)XP Rabbit mAb #8242" (trade name)). Subsequently, they were incubated at room temperature for 1 hour with anti-rabbit secondary antibody (Thermo Fisher, "Goat anti-Rabbit IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor® 488" (trade name)). Finally, they were stained with nuclear stain (Thermo Fisher, "NucBlue" (brand name)). TM Incubation was performed at room temperature for 30 minutes using "Fixed Cell Stain ReadyProbes® reagent" (trade name). Subsequently, the number of nuclear positive cells was measured using a fluorescence microscope.

[0072] [Table 5]

[0073] The results above confirmed that UV irradiation significantly localizes NF-κB within the nucleus. On the other hand, it was revealed that even with UV irradiation, the addition of 5 ppm or 20 ppm of naringenin significantly inhibited the nuclear localization of NF-κB. These results suggest that naringenin may have an inhibitory effect on the NF-κB activation pathway.

Claims

1. An anti-inflammatory agent characterized by containing naringenin.

2. The anti-inflammatory agent according to claim 1, wherein the inflammation is chronic inflammation of the human epidermis.

3. An anti-inflammatory agent according to claim 1 or 2, which alters the expression of at least one gene selected from the group consisting of COX2, IL-6, TNF-α, MMP-1, and HO-1.

4. An anti-inflammatory agent according to claim 1 or 2, which inhibits the translocation of NF-κB protein to the nucleus.

5. A composition for suppressing chronic inflammation, characterized by containing naringenin and a pharmaceutically acceptable carrier.

6. The composition for suppressing chronic inflammation according to claim 5, which is a cosmetic or a topical skin preparation.

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