Composition for suppressing skin sagging caused by fatigue

Abstract

To identify a component capable of more effectively suppressing a decrease in adipose stem cells in the skin, and to provide a composition that contributes to the suppression of skin sagging based on a decrease in the number of adipose stem cells caused by fatigue-transmitting substances.SOLUTION: The present invention provides a composition for suppressing skin sagging caused by fatigue, comprising an adipose layer decrease inhibitor. By using the adipose layer decrease inhibitor, a decrease in the number of adipose stem cells caused by fatigue-transmitting substances can be suppressed, thereby significantly suppressing sagging of the skin.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a composition for preventing sagging skin caused by fatigue. [Background technology]

[0002] Fatigue is known to increase various factors in the blood.

[0003] Deep within the epidermis and dermis of the skin is subcutaneous adipose tissue, which acts as a cushion against external physical forces. A decrease in subcutaneous adipose tissue reduces skin tension (Non-Patent Document 1), and a further decrease in skin tension promotes wrinkle formation. Subcutaneous adipose tissue is permeated with blood vessels, and is known to be susceptible to the influence of blood vessels. However, the effects of fatigue mediators in the blood on subcutaneous fat and adipose stem cells, which give rise to various tissues, are unknown. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] Quatresooz P, Thirion L, Pierard-Franchimont C, Pierard GE. The riddle of genuine skin microrelief and wrinkles. Int J Cosmet Sci. 2006 Dec;28(6):389-95. Summary of the Invention [Problem to be solved by the invention]

[0005] The present invention has newly discovered that fatigue mediators reduce the number of adipose stem cells in the skin. Based on this new finding, the present invention aims to discover components that can further suppress the decrease in the number of adipose stem cells in the skin, and to provide a composition that contributes to suppressing fatigue-induced skin sagging. [Means for solving the problem]

[0006] After extensive research, the inventors discovered that a specific active ingredient is effective in solving these problems, leading to the completion of this research. The composition of the present invention contains a fatigue mediator, i.e., an ingredient that can suppress the decrease in the number of adipose stem cells caused by blood factors that increase with fatigue, thereby suppressing the loss of fat layer and preventing skin sagging.

[0007] That is, the gist of the present invention is as follows.

[0008] [1] A composition for inhibiting sagging skin caused by fatigue, containing an agent for inhibiting fat layer reduction. [2] A composition for inhibiting sagging skin due to fatigue described in [1], characterized in that the reduction in the fat layer is due to a decrease in the number of adipose stem cells. [3] A composition for inhibiting skin sagging due to fatigue described in [2], characterized in that the decrease in the number of adipose stem cells is due to fatigue transmitters. [4] A composition for inhibiting skin sagging due to fatigue according to [3], wherein the fatigue transmitter is 7β-hydroxycholesterol. [5] A composition for inhibiting sagging skin due to fatigue according to any one of [1] to [4], wherein the agent for inhibiting fat layer reduction is at least one selected from the group consisting of pyrroloquinoline quinone (PQQ), its salts, and evening primrose extract. [Effects of the Invention]

[0009] By using the present invention, it is possible to effectively prevent sagging skin caused by fatigue. DETAILED DESCRIPTION OF THE INVENTION

[0010] The composition of the present invention contains an effective amount of an agent for inhibiting fat layer reduction.

[0011] (Fat layer reduction inhibitor) As mentioned above, the present inventors have newly discovered that fatigue mediators affect the decrease in the number of adipose stem cells in the skin. Fatigue mediators refer to blood factors that increase due to fatigue, including, but not limited to, 7β-hydroxycholesterol, inflammatory cytokines, oxidative stress, lactic acid, cortisol, and adrenaline.

[0012] Types of fatigue include physical fatigue, mental and nervous fatigue, pathological fatigue, etc. Although not particularly limited, physical fatigue and mental and nervous fatigue are preferred. Fatigue can be caused by everyday life, sports, illness, etc., but physiological fatigue that occurs in everyday life is preferred. Examples of daily life include housework, childcare, commuting to work or school, nursing care, work, school life, etc., and fatigue caused by lack of sleep, desk work, and exposure to ultraviolet rays is particularly preferred, with fatigue caused by lack of sleep and desk work being more preferred.

[0013] These fatigue mediators can be produced by various tissues in the body, but the effects of these substances on the skin have not been fully investigated until now.In the examples described below, it has been newly discovered that 7β-hydroxycholesterol produced by whole-body fatigue reaches skin tissue via the blood and causes a decrease in the number of adipose stem cells localized in the skin.Therefore, when the number of adipose stem cells localized in the skin decreases, the differentiation of adipose stem cells is inhibited, leading to thinning (decrease) of the fat layer, which ultimately causes the skin to lose firmness and sag.

[0014] Therefore, it has become clear that, although not limited to, by finding a component that can inhibit the thinning (reduction) of the fat layer due to the involvement of fatigue transmitters produced by tissues other than the skin, sagging skin can be significantly inhibited.

[0015] In the examples described below, it has been discovered that salts of pyrroloquinoline quinone (hereinafter also referred to as PQQ) and evening primrose extract are useful ingredients that can suppress the decrease in the number of adipose stem cells caused by fatigue transmitters produced in tissues other than the skin.

[0016] Examples of salts of pyrroloquinoline quinone include alkali metal salts, alkaline earth metal salts, and ammonium salts. Examples of alkali metal salts include sodium salts, potassium salts, and lithium salts. Examples of alkaline earth metal salts include calcium salts and magnesium salts.

[0017] As pyrroloquinoline quinone or a salt thereof, an alkali metal salt of pyrroloquinoline quinone is preferred, a sodium salt of pyrroloquinoline quinone is more preferred, and a disodium salt of pyrroloquinoline quinone is even more preferred.

[0018] Commercially available pyrroloquinoline quinone or a salt thereof may be used. Furthermore, pyrroloquinoline quinone or a salt thereof may be, for example, natto, soybean, cocoa powder, cacao mass, cacao, parsley, bell pepper, or other products containing pyrroloquinoline quinone or a salt thereof. Commercially available pyrroloquinoline quinone or a salt thereof may also be used. Furthermore, pyrroloquinoline quinone or a salt thereof may be used singly or in combination of two or more.

[0019] In this specification, the plant extract may be a crude extract extracted from the whole plant or from an extracting part (flower, inflorescence, flower bud, spike, leaf, branch, branch, leaf, rhizome, root bark, root, bark, fruit, pericarp, legume, seed, etc.) of the plant as is, or may be a product obtained by further purification or concentration, or may be obtained by synthesis, or a commercially available product may be used. The method for obtaining the plant extract is not particularly limited, and conventional extraction methods, purification methods, concentration methods, synthesis methods, dry powdering methods, etc. may be used. Although not limited, the part from which evening primrose extract is extracted is preferably, for example, the seeds and / or flowers, and more preferably the seeds.

[0020] For example, evening primrose extract can be extracted from the seeds of evening primrose, a plant of the Onagraceae family, with at least one solvent selected from the group consisting of water, 1,3-butylene glycol (BG), and ethanol. Alternatively, plant extracts commercially available as cosmetic ingredients may also be used.

[0021] The total content of the fat layer reduction inhibitor is not particularly limited as long as the effects of the present invention are achieved, but examples include 0.000001 mass% or more, 0.00001 mass% or more, 0.00005 mass% or more, 0.0001 mass% or more, 0.0005 mass% or more, 0.001 mass% or more, 0.005 mass% or more, and 0.01 mass% or more. The total content of the fat layer reduction inhibitor is, for example, 1% by mass or less, 0.5% by mass or less, 0.1% by mass or less, 0.05% by mass or less, or 0.03% by mass or less. The total content of the fat layer reduction inhibitor may be, for example, 0.000001 to 1 mass%, 0.00001 to 1 mass%, 0.0001 to 0.5 mass%, 0.001 to 0.1 mass%, 0.005 to 0.05 mass%, or 0.01 to 0.03 mass%.

[0022] In one embodiment, when pyrroloquinoline quinone or a salt thereof is contained as the fat layer reduction inhibitor, the content of pyrroloquinoline quinone or a salt thereof alone may be, for example, 0.0001% by mass or more, 0.0005% by mass or more, 0.001% by mass or more, 0.005% by mass or more, or 0.01% by mass or more. The content of pyrroloquinoline quinone or a salt thereof alone is, for example, 1% by mass or less, 0.1% by mass or less, or 0.03% by mass or less. The content of pyrroloquinoline quinone or a salt thereof is, for example, 0.0001 to 1 mass%, 0.0005 to 0.1 mass%, 0.001 to 0.03 mass%, 0.005 to 0.03 mass%, or 0.01 to 0.03 mass%.

[0023] In one embodiment, when evening primrose extract is contained as the fat layer reduction inhibitor, the content of evening primrose extract alone is, for example, 0.0000001 mass% or more, 0.0000005 mass% or more, 0.000001 mass% or more, 0.000005 mass% or more, etc. The content of evening primrose extract alone may be, for example, 1% by mass or less, 0.1% by mass or less, 0.01% by mass or less, 0.005% by mass or less, 0.001% by mass or less, 0.0005% by mass or less, 0.0001% by mass or less, 0.00005% by mass or less, and the like. The content of evening primrose extract alone can be, for example, 0.0000001 to 1 mass%, 0.0000005 to 0.5 mass%, 0.000001 to 0.1 mass%, 0.000005 to 0.05 mass%, 0.000005 to 0.01 mass%, or 0.000005 to 0.001 mass%.

[0024] In another embodiment, two or more types of fat layer reduction inhibitors may be contained. For example, when pyrroloquinoline quinone and evening primrose extract are used in combination, the blending ratio thereof is not particularly limited as long as the effects of the present invention are achieved. However, examples of the content of evening primrose extract relative to 1 part by mass of pyrroloquinoline quinone include 0.00001 parts by mass or more, 0.00005 parts by mass or more, 0.0001 parts by mass or more, 0.0005 parts by mass or more, and the like. The content of evening primrose extract relative to 1 part by mass of pyrroloquinoline quinone is, for example, 0.05 parts by mass or less, 0.01 parts by mass or less, 0.005 parts by mass or less, 0.001 parts by mass or less, 0.0008 parts by mass or less, etc. The content of evening primrose extract relative to 1 part by mass of pyrroloquinoline quinone is, for example, 0.00001 to 0.05 parts by mass, 0.00005 to 0.01 parts by mass, 0.0001 to 0.005 parts by mass, 0.0005 to 0.001 parts by mass, or 0.0005 to 0.0008 parts by mass.

[0025] The composition of the present invention may contain other ingredients in addition to the above-mentioned fat layer reduction inhibitor, as long as the effects of the present invention are not impaired.The composition of the present invention can be used in combination with, for example, drugs used in ordinary external treatments.The combination with drugs that make the effects of the present invention more likely to be exhibited is particularly preferred.

[0026] Examples of these other ingredients include anti-inflammatory agents, refreshing agents, disinfectants, vitamins, organic acids, moisturizing ingredients, polyhydric alcohols, scrubbing agents, UV-absorbing ingredients, UV-scattering ingredients, astringent ingredients, peptides or derivatives thereof, amino acids or derivatives thereof, cleansing ingredients, keratin softening ingredients, cell activating ingredients, anti-aging ingredients, anti-glycation ingredients, blood circulation promoting ingredients, whitening ingredients, polyphenols, etc. In the composition of the present invention, these ingredients may be used alone or in combination of two or more.

[0027] Examples of the anti-inflammatory agent include plant-derived components, allantoin and derivatives thereof, glycyrrhetinic acid and derivatives thereof, glycyrrhizinic acid and salts or derivatives thereof, salicylic acid derivatives, aminocaproic acid, azulene and derivatives thereof, zinc oxide, calamine, tocopherol acetate, hydrocortisone, prednisolone, and salts thereof.

[0028] Examples of the cooling agent include menthol and its derivatives, camphor, terpenes such as borneol, geraniol, cineole, anethole, limonene, and eugenol (which may be in the d-, l-, or dl-form); and essential oils such as eucalyptus oil, bergamot oil, peppermint oil, cool mint oil, spearmint oil, fennel oil, peppermint oil, cinnamon oil, rose oil, and turpentine.

[0029] Examples of the disinfectants include isopropylmethylphenol, chlorhexidine, salicylic acid, benzalkonium chloride, acrinol, ethanol, benzethonium chloride, cresol, gluconic acid and its derivatives, povidone-iodine, potassium iodide, iodine, triclocarban, triclosan, photosensitizer No. 101, photosensitizer No. 201, paraben, phenoxyethanol, 1,2-pentanediol, alkyldiaminoglycine hydrochloride, piroctoolamine, and miconazole.

[0030] The vitamins may be either water-soluble or oil-soluble, and examples thereof include vitamin B6s such as pyridoxine, pyridoxal, pyridoxamine, 5'-pyridoxal phosphate, and salts thereof (e.g., pyridoxine hydrochloride, pyridoxine acetate, pyridoxal hydrochloride, pyridoxamine hydrochloride); pantothenic acids such as pantothenic acid, calcium pantothenate, pantothenyl alcohol (panthenol), D-pantetheine, D-pantethine, coenzyme A, pantothenyl ethyl ether, and salts thereof; nicotinic acids such as nicotinic acid, dl-α-tocopherol nicotinate, benzyl nicotinate, methyl nicotinate, β-butoxyethyl nicotinate, 1-(4-methylphenyl)ethyl nicotinate, nicotinamide, and salts thereof; γ-oryzanol, thiamine, dibenzoylthiamine, thiamine cetyl, thiamine monophosphate, thiamine diphosphate, and thiamine triphosphate. Vitamin B1 compounds such as esters and their salts (e.g., dibenzoylthiamine hydrochloride, thiamine hydrochloride, thiamine cetyl hydrochloride, thiamine thiocyanate, thiamine lauryl hydrochloride, thiamine nitrate, thiamine monophosphate, thiamine lysine salt, thiamine triphosphate, thiamine monophosphate phosphate, thiamine diphosphate hydrochloride, thiamine triphosphate monophosphate); vitamin B2 compounds such as riboflavin, flavin mononucleotide, flavin adenine dinucleotide, riboflavin butyrate, riboflavin tetrabutyrate, riboflavin 5'-phosphate sodium, riboflavin tetranicotinate, and their salts; biotin compounds such as biotin, biocytin, and their salts; folates such as folic acid, pteroylglutamic acid, and their salts; vitamin B12 compounds such as cyanocobalamin, hydroxocobalamin, deoxyadenosylcobalamin, and their salts;Water-soluble vitamin C compounds such as ascorbic acid, dehydroascorbic acid, ascorbic acid phosphate, ascorbic acid 2-glucoside, 2-O-ethyl ascorbic acid, 3-O-ethyl ascorbic acid, glyceryl ascorbic acid, bisglyceryl ascorbic acid, and alkylglyceryl ascorbic acid, and their salts (e.g., sodium ascorbate, sodium ascorbyl phosphate, and magnesium ascorbyl phosphate); vitamin E compounds such as dl-α-tocopherol, dl-α-tocopherol acetate, dl-α-tocopherol succinate, dl-α-tocopherol calcium succinate, tocopherol linoleate, tocopherol (linoleate / oleate), tocopherol, and potassium (ascorbyl / tocopheryl) phosphate; ascorbigen-A, ascorbic acid stearate, and ascorbyl palmitate. Vitamin C and its salts, such as ascorbyl tetra-2-hexyldecanoate, L-ascorbyl dipalmitate, and ascorbyl tetra-2-hexyldecanoate; vitamin Ds, such as ergocalciferol and cholecalciferol; vitamin Ks, such as phylloquinone and falnoquinone; vitamin A, such as retinol, retinal, retinoic acid, 3-dehydroretinol, 3-dehydroretinal, 3-dehydroretinoic acid, and hydrogenated retinol, and their derivatives, palmitic acid, Vitamin A derivatives such as retinol phosphate, retinol propionate, retinol linoleate, and retinol acetate; provitamin A derivatives such as α-carotene, β-carotene, γ-carotene, and cryptoxanthin; hesperidin derivatives such as ferulic acid, hesperidin, and glucosyl herperidin; vitamin-like factors such as ubiquinone, glucurolactone, glucuronic acid amide, orotic acid, L-carnitine, α-lipoic acid, and orotic acid;

[0031] Examples of the organic acids include gluconic acid, aspartic acid, aminoethylsulfonic acid, citric acid, glutamic acid, succinic acid, oxalic acid, fumaric acid, malonic acid, maleic acid, propionic acid, malic acid, salicylic acid, glycolic acid, phytic acid, tartaric acid, acetic acid, lactic acid, pantothenic acid, glycyrrhetinic acid, alginic acid, ascorbic acid, benzoic acid, adipic acid, glutamic acid, azelaic acid, and salts thereof. Examples of the salts include salts of mineral acids such as sulfuric acid, hydrochloric acid, and phosphoric acid, salts of organic acids such as maleic acid and methanesulfonic acid, salts of alkali metals such as sodium and potassium, alkaline earth metal salts, ammonium salts, salts of basic amino acids, and amine salts such as triethanolamine.

[0032] Examples of the moisturizing components include diglycerin trehalose; mucopolysaccharides such as heparinoids and sodium chondroitin sulfate; MPC polymers; collagen, elastin, keratin, chitin, chitosan, and the like, and their hydrolysates; amino acids such as glycine, aspartic acid, and arginine; natural moisturizing factors such as sodium lactate, urea, and sodium pyrrolidonecarboxylate; lipids such as ceramide, cholesterol, phytosterol, and phospholipids; plant extracts such as chamomile extract, hamamelis extract, tea extract, perilla extract, and grapefruit extract; polyhydric alcohols or derivatives thereof such as glycerin, polyoxyalkylene alkyl glucoside, PEG / PPG / polybutylene glycol-8 / 5 / 3 glycerin, and glyceryl glucoside, and hydroxyethyl urea.

[0033] The polyhydric alcohol is preferably one having 2 to 10 carbon atoms, and examples thereof include glycerin, diglycerin, triglycerin, propylene glycol, dipropylene glycol, 1,3-butanediol, ethylene glycol, diethylene glycol, isoprene glycol, 1,3-butylene glycol, sorbitol, xylitol, erythritol, mannitol, pentanediol, hexanediol, octanediol, decanediol, and neopentyl glycol.

[0034] Examples of the scrubbing agent include apricot kernel powder, almond shell powder, apricot kernel powder, sodium chloride granules, olive kernel powder, seawater dried granules, candelilla wax, walnut shell powder, cherry kernel powder, coral powder, charcoal powder, hazelnut shell powder, polyethylene powder, and silicic anhydride.

[0035] Examples of the ultraviolet absorbing component include octyl triazone, dimethoxybenzylidene dioxoimidazolidine octyl propionate, 2-ethylhexyl paramethoxycinnamate, phenylbenzimidazole sulfonic acid, diethylaminohydroxybenzoyl hexyl benzoate, bisethylhexyloxyphenol methoxyphenyl triazine, trisethylhexyloxycarbonylanilinotriazine, t-butylmethoxydibenzoylmethane, paraaminobenzoic acid and derivatives thereof, octyl paradimethylaminobenzoate, dihydroxybenzophenone, and methylenebisbenzotriazolyltetramethylbutylphenol.

[0036] Examples of the ultraviolet scattering component include inorganic compounds such as hydrous silicic acid, zinc silicate, cerium silicate, titanium silicate, zirconium oxide, cerium oxide, titanium oxide, zinc oxide, iron oxide, and silicic anhydride; these inorganic compounds coated with inorganic powder such as hydrous silicic acid, aluminum hydroxide, mica, and talc; compounds composited with resin powder such as polyamide, polyethylene, polyester, polystyrene, and nylon; and compounds further treated with silicone oil, aluminum salt of a fatty acid, or the like.

[0037] Examples of the astringent component include metal salts such as ethanol, zinc sulfate, aluminum chloride, and zinc sulfocarbonate, and organic acids such as tannic acid.

[0038] Examples of the above peptides or derivatives thereof include keratin hydrolyzed peptides, hydrolyzed keratin, collagen, fish-derived collagen, atelocollagen, gelatin, elastin, elastin hydrolyzed peptides, collagen hydrolyzed peptides, hydrolyzed collagen, hydroxypropylammonium chloride hydrolyzed collagen, elastin hydrolyzed peptides, conchiolin hydrolyzed peptides, hydrolyzed conchiolin, silk proteolytic peptides, hydrolyzed silk, sodium lauroyl hydrolyzed silk, soybean proteolytic peptides, hydrolyzed soybean protein, wheat protein, wheat proteolytic peptides, hydrolyzed wheat protein, casein hydrolyzed peptides, and acylated peptides (palmitoyl oligopeptide, palmitoyl pentapeptide, palmitoyl tetrapeptide, etc.).

[0039] Examples of the amino acids or derivatives thereof include betaine (trimethylglycine), proline, hydroxyproline, arginine, lysine, serine, glycine, alanine, phenylalanine, β-alanine, threonine, glutamic acid, glutamine, asparagine, aspartic acid, cysteine, cystine, methionine, leucine, isoleucine, valine, histidine, threonine, tyrosine, taurine, γ-aminobutyric acid, γ-amino-β-hydroxybutyric acid, carnitine, carnosine, creatine, epsilon-aminocaproic acid, tryptophan, ornithine, etc. Furthermore, these amino acids or derivatives thereof may be in the form of a solvate such as a hydrate, and may be in any of the d-, l-, or dl-forms.

[0040] Examples of the cleansing component include soaps selected from alkali metal salts such as potassium laurate, potassium myristate, potassium palmitate, and potassium stearate, alkanolamide salts, and amino acid salts; amino acid surfactants such as sodium cocoyl glutamate, sodium cocoyl methyl taurate, sodium cocoyl methyl taurate, and potassium cocoyl methyl glutamate; ether sulfate ester salts such as sodium laureth sulfate; ether carboxylate salts such as sodium lauryl ether acetate; sulfosuccinate ester salts such as sodium alkyl sulfosuccinate; and fatty acids such as coconut oil fatty acid monoethanolamide and coconut oil fatty acid diethanolamide. Examples of such surfactants include fatty acid alkanolamides; monoalkyl phosphate ester salts such as sodium lauryl phosphate and sodium polyoxyethylene lauryl ether phosphate; betaine-type amphoteric surfactants such as coconut oil fatty acid amidopropyl dimethylaminoacetic acid betaine, lauryl dimethylaminoacetic acid betaine, 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazolinium betaine, lauryl hydroxysulfobetaine, cocamidopropyl betaine, and lauroyl amidoethyl hydroxyethyl carboxymethyl betaine hydroxypropyl sodium phosphate; and amino acid-type amphoteric surfactants such as sodium lauryl aminopropionate.

[0041] Examples of the keratin softening ingredients include lanolin, lactic acid, salicylic acid, gluconic acid, glycolic acid, citric acid, malic acid, fruit acid, phytic acid, urea, sulfur, and the like.

[0042] Examples of the cell-activating components include components derived from plants (e.g., bilberry), amino acids such as γ-aminobutyric acid; vitamins such as retinol, thiamine, riboflavin, pyridoxine hydrochloride, and pantothenic acids; α-hydroxy acids such as glycolic acid and lactic acid; tannins, flavonoids, saponins, and photosensitizer No. 301.

[0043] Examples of the anti-aging ingredients include hydrolyzed soy protein, retinoids (retinol and its derivatives, retinoic acid, retinal, etc.), pangamic acid, kinetin, ursolic acid, turmeric extract, sphingosine derivatives, silicon, silicic acid, N-methyl-L-serine, mevalonolactone, etc.

[0044] Examples of the anti-glycation component include plant extracts such as Budreja axillaris leaf extract, Amla fruit, fruit juice or extracts thereof, L-arginine, L-lysine, hydrolyzed casein, hydrolyzable tannin, carnosine, etc.

[0045] Examples of the blood circulation-promoting component include components derived from plants (e.g., ginseng, angelica tree, arnica, ginkgo, fennel, emmeisou, Dutch oak, chamomile, Roman chamomile, carrot, gentian, burdock, rice, hawthorn, shiitake mushroom, ginger, European hawthorn, European juniper, cnidium rhizome, Swertia japonica, thyme, clove, tangerine peel, chili pepper, angelica acutiloba, peach kernel, spruce, carrot, garlic, butcher's broom, grape, peony, horse chestnut, melissa, yuzu, coix seed, ryokucha, rosemary, rose hip, tangerine peel, angelica acutiloba, spruce, peach, apricot, walnut, corn, golden chamomile, etc.); acetylcholine, ichthammol, cantharides tincture, gamma-oryzanol, cepharanthine, tolazoline, tocopherol nicotinate, glucosyl hesperidin, etc.

[0046] Examples of the whitening ingredients include tocopherol, tranexamic acid, ascorbic acid and its salts, vitamin C such as ascorbic acid derivatives (sodium ascorbyl phosphate, magnesium ascorbyl phosphate, ascorbyl tetra-2-hexyldecanoate, 2-O-ethyl ascorbic acid, 3-O-ethyl ascorbic acid, ascorbic acid glucoside, etc.), arbutin, kojic acid, placenta, ellagic acid, nicotinamide, hydroquinone, potassium 4-methoxysalicylate, linoleic acid and its derivatives.

[0047] Examples of the polyphenols include flavonoid polyphenols such as curcuminoids, flavanones, stilpenoids, polymethoxyflavonoids, flavonols, xanthonoids, chalcones, lignoids, flavanols, and isoflavones, and phenolic acid polyphenols.

[0048] (pH) The pH of the composition of the present invention is usually 2.0 to 9.0, preferably 3.0 to 8.5, more preferably 3.5 to 8.0, and even more preferably 4.0 to 8.0. This pH can be adjusted by using a pH adjuster.

[0049] (Method of producing the composition of the present invention) The method for producing the composition of the present invention is not particularly limited, and the composition can be produced by a conventional method by appropriately selecting and mixing the above-mentioned other components to be blended as needed, bases or carriers required for producing various preparations, additives, etc., with the fat layer reduction inhibitor. As the fat layer reduction inhibitor, a commercially available product or a synthetic product may be used.

[0050] The composition of the present invention can also be prepared into an external composition in various formulations by mixing the fat layer reduction inhibitor and other ingredients described above, if necessary, with a base or carrier commonly used in cosmetics, pharmaceuticals, quasi-drugs, foods, etc., and the additives described below, according to a conventional method, and emulsifying or solubilizing as necessary.

[0051] Examples of the base or carrier include hydrocarbons such as liquid paraffin, squalane, petrolatum, gelling hydrocarbons (such as Plastibase), ozokerite, α-olefin oligomers, polyethylene wax, and light liquid paraffin; silicone oils such as methyl polysiloxane, highly polymerized methyl polysiloxane, cyclic silicone, alkyl-modified silicone, amino-modified silicone, polyether-modified silicone, polyglycerin-modified silicone, silicone / alkyl chain co-modified polyether-modified silicone, silicone / alkyl chain co-modified polyglycerin-modified silicone, polyether-modified branched silicone, polyglycerin-modified branched silicone, acrylic silicone, phenyl-modified silicone, and silicone resin; oils and fats such as coconut oil, olive oil, rice bran oil, and shea butter; waxes such as jojoba oil, beaucospray, candelilla wax, and lanolin; cetanol, cetostearyl alcohol, and the like. Higher alcohols such as ethanol, stearyl alcohol, behenyl alcohol, octyldodecanol, isostearyl alcohol, phytosterol, and cholesterol; cellulose derivatives such as ethyl cellulose, hydroxypropyl cellulose, and hydroxypropylmethyl cellulose; polyvinylpyrrolidone; carrageenan; polyvinyl butyrate; polyethylene glycol; dioxane; butylene glycol adipate polyester; esters such as diisopropyl adipate, isopropyl myristate, octyldodecyl myristate, isopropyl palmitate, cetyl palmitate, isononyl isononanoate, and pentaerythritol tetra-2-ethylhexanoate; polysaccharides such as dextrin and maltodextrin; vinyl polymers such as carboxyvinyl polymers and alkyl-modified carboxyvinyl polymers; lower alcohols such as ethanol and isopropanol;Examples of suitable bases or carriers include glycol ethers such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monopropyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monopropyl ether, diethylene glycol monobutyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monoethyl ether, and dipropylene glycol monopropyl ether; and water. The bases or carriers described above may be used alone or in combination of two or more. The amounts used are appropriately selected from ranges known to those skilled in the art.

[0052] The composition of the present invention may contain known additives added to cosmetics, pharmaceuticals, quasi-drugs, foods, etc., within the scope of not impairing the effects of the present invention, such as surfactants, stabilizers, antioxidants, colorants, pearlescent agents, dispersants, chelating agents, pH adjusters, preservatives (antiseptics), thickeners, irritation reducers, texture improvers, excipients, lubricants, binders, disintegrants, solvents, oils and fats, emulsifiers, dispersants, suspending agents, stabilizers, thickeners, sweeteners, colorants, flavorings, antioxidants, acidulants, and food additives such as fruit juice. These additives may be used alone or in combination of two or more.

[0053] The surfactant may be any of a nonionic surfactant, a cationic surfactant, an anionic surfactant, an amphoteric surfactant, and the like, and examples thereof include sorbitan fatty acid esters such as sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, diglycerol sorbitan penta-2-ethylhexylate, and diglycerol sorbitan tetra-2-ethylhexylate; propylene glycol fatty acid esters such as propylene glycol monostearate; hydrogenated castor oil derivatives such as polyoxyethylene hydrogenated castor oil 40 (HCO-40), polyoxyethylene hydrogenated castor oil 50 (HCO-50), polyoxyethylene hydrogenated castor oil 60 (HCO-60), and polyoxyethylene hydrogenated castor oil 80; polyoxyethylene monolaurate; Examples of surfactants include polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene (20) sorbitan (polysorbate 20), polyoxyethylene (20) sorbitan monostearate (polysorbate 60), polyoxyethylene (20) sorbitan monooleate (polysorbate 80), and polyoxyethylene (20) sorbitan isostearate; polyoxyethylene monoglyceryl cocoate; glycerin alkyl ethers; alkyl glucosides; polyoxyalkylene alkyl ethers such as polyoxyethylene cetyl ether; amines such as stearylamine and oleylamine; and silicone surfactants such as polyoxyethylene-methylpolysiloxane copolymer, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, and PEG-9 polydimethylsiloxyethyl dimethicone.

[0054] Examples of the stabilizer include sodium polyacrylate, dibutylhydroxytoluene, and butylhydroxyanisole.

[0055] Examples of the antioxidant include dibutylhydroxytoluene, butylhydroxyanisole, sorbic acid, sodium sulfite, ascorbic acid, sodium ascorbate, ascorbyl stearate, ascorbyl sodium stearate, ascorbyl palmitate, tocopherol, tocopherol acetate, tocotrienol, bisulfite, sodium hyposulfite, sulfur dioxide, calcium disodium EDTA, erythorbic acid, sodium erythorbate, L-cysteine ​​hydrochloride, ubiquinones such as coenzyme Q10, lignans such as sesamin, curcumin, capsaicin, gingerol, resveratrol, anthocyanin, cyanidin, bilberry extract, and analogs or derivatives thereof. Of these, dibutylhydroxytoluene, ascorbic acid, ascorbyl palmitate, tocopherol, tocopherol acetate, coenzyme Q10, resveratrol, anthocyanin, sesamin, curcumin, capsaicin, gingerol, and bilberry extract are preferred.

[0056] Examples of the colorant include inorganic pigments and natural dyes.

[0057] Examples of the pearly luster imparting agent include ethylene glycol distearate, ethylene glycol monostearate, and triethylene glycol distearate.

[0058] Examples of the dispersant include sodium pyrophosphate, sodium hexametaphosphate, polyvinyl alcohol, polyvinylpyrrolidone, methyl vinyl ether / maleic anhydride crosslinked copolymer, and organic acids.

[0059] Examples of the chelating agent include EDTA disodium salt, EDTA calcium disodium salt, and the like.

[0060] Examples of the pH adjuster include inorganic acids (phosphoric acid, hydrochloric acid, sulfuric acid, etc.), organic acids (lactic acid, sodium lactate, citric acid, sodium citrate, succinic acid, sodium succinate, gluconic acid, sodium malate, etc.), potassium carbonate, sodium bicarbonate, carbon dioxide, inorganic bases (potassium hydroxide, sodium hydroxide, etc.), and organic bases (triethanolamine, diisopropanolamine, triisopropanolamine, etc.).

[0061] Examples of the preservative (antiseptic) include benzoic acid, sodium benzoate, dehydroacetic acid, sodium dehydroacetate, isobutyl parahydroxybenzoate, isopropyl parahydroxybenzoate, butyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, benzyl parahydroxybenzoate, methyl parahydroxybenzoate, phenoxyethanol, chlorobutanol, benzyl alcohol, phenethyl alcohol, sorbic acid, and salts thereof.

[0062] Examples of the thickener include vinyl thickeners such as polyvinyl alcohol, polyvinylpyrrolidone, and carboxyvinyl polymers; cellulose thickeners such as methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, and carboxyethylcellulose; guar gum, pectin, pullulan, gelatin, locust bean gum, carrageenan, agar, glucomannan, curdlan, gellan gum, xanthan gum, acrylates / alkyl methacrylate copolymers, polyethylene glycol, bentonite, alginic acid, propylene glycol alginate, macrogol, sodium chondroitin sulfate, hyaluronic acid, sodium hyaluronate, (hydroxyethyl acrylate / sodium acryloyldimethyltaurate) copolymer, and (ammonium acryloyldimethyltaurate / vinylpyrrolidone) copolymer.

[0063] Examples of the irritation reducer include cellulose derivatives such as methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, and hydroxypropylmethyl cellulose, polyvinylpyrrolidone, polyvinyl alcohol, acrylic acid polymers, gelatin, gum arabic, pullulan, pregelatinized starch, agar, tragacanth, sodium alginate, propylene glycol alginate, licorice extract, and 2-methacryloyloxyethyl phosphorylcholine.

[0064] Examples of the feel improver include diisostearyl malate.

[0065] Examples of the excipient include lactose, sucrose, sodium chloride, glucose, starch, calcium carbonate, kaolin, microcrystalline cellulose, silicic acid, and the like.

[0066] Examples of the binder include polysaccharides such as refined sucrose, glucose, trehalose, lactose, maltose, saccharin sodium, aspartame, acesulfame potassium, and maltodextrin; corn starch, potato starch, wheat starch, and pregelatinized starches thereof; sugar alcohols such as mannitol, sorbitol, xylitol, erythritol, and sucralose; cellulose-based polymers such as crystalline cellulose, methyl cellulose, ethyl cellulose, hypromellose, hydroxypropyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, carmellose calcium, hypromellose phthalate, and cellulose acetate phthalate; calcium phosphate; and polyvinylpyrrolidone.

[0067] Examples of the disintegrants include starch, low-substituted hydroxypropyl cellulose, carboxymethylcellulose calcium, croscarmellose sodium, hydroxypropyl starch, partially pregelatinized starch, sodium alginate, agar powder, sodium hydrogen carbonate, calcium carbonate, sodium lauryl sulfate, monoglyceride stearate, and lactose.

[0068] Examples of the lubricant include stearic acid, magnesium stearate, calcium stearate, polyoxyl stearate, cetanol, talc, hydrogenated oil, sucrose fatty acid ester, dimethylpolysiloxane, beeswax, white beeswax, borax, and polyethylene glycol.

[0069] Examples of the fats and oils include natural vegetable oils such as palm oil, palm kernel oil, coconut oil, corn oil, sunflower oil, safflower oil, peanut oil, cocoa butter, cottonseed oil, soybean oil, rapeseed oil, rice oil, rice germ oil, perilla oil, and linseed oil; animal fats and oils such as beef tallow, milk fat, lard, cacao butter, fish oil, whale oil, butter, and butter oil; hardened oils of these; glycerides (e.g., glycerides, diglycerides, and triglycerides) of fatty acids (including medium-chain fatty acids); meadowfoam oil; and beeswax.

[0070] Examples of the emulsifiers, dispersants, suspending agents, and stabilizers include polyhydric alcohols such as polyethylene glycol, propylene glycol, glycerin, and sorbitol; synthetic emulsifiers such as glycerin fatty acid esters, sucrose fatty acid esters, and polyglycerin fatty acid esters; natural emulsifiers such as lecithins, saponin, plant sterols, and milk fat globule membranes; and sodium carboxymethylcellulose, kaolin, xanthan gum, methylcellulose, and tragacanth.

[0071] Examples of the sweetener include sucrose, fructose, maltose, trehalose, licorice extract, saccharin, saccharin sodium, sucralose, stevia processed sweetener, Monk fruit extract, aspartame, acesulfame potassium, erythritol, sorbitol, xylitol, maltitol, reduced starch syrup, and reduced maltose starch syrup.

[0072] Examples of the acidulant include adipic acid, itaconic acid, citric acid, potassium citrate, glucono-delta-lactone, gluconic acid, succinic acid, sodium succinate, sodium acetate, tartaric acid, sodium tartrate, carbon dioxide, lactic acid, sodium lactate, glacial acetic acid, phytic acid, fumaric acid, sodium fumarate, malic acid, and phosphoric acid.

[0073] Examples of the fruit juice include lemon juice, orange juice, berry juice, apple juice, banana juice, and the like.

[0074] The form of the composition of the present invention is not particularly limited, and examples thereof include ointments, solutions, suspensions, emulsions (milky lotions and creams), gels, liniments, lotions, patches, mists, foams, aerosols, sticks, powders, granules, tablets (including plain tablets, sugar-coated tablets, orally disintegrating tablets, chewable tablets, effervescent tablets, troches, and film-coated tablets), detergents, soaps, solid preparations, capsules, films, confectioneries (including candies, gummies, and nougat), syrups, drinks, juices, soft drinks, and tea; solid preparations such as biscuits, tablets, granular powders, powders, and capsules; and semi-liquid preparations such as pastes, jellies, soups, seasonings, and dressings. These preparations can be produced by conventional methods, for example, the methods described in the General Provisions for Preparations of the Japanese Pharmacopoeia, 17th Edition.

[0075] When the composition of the present invention is in the form of a cosmetic, it can be used in the form of, for example, basic cosmetics such as creams, milky lotions, lotions, serums, essences, facial cleansers, cleansing agents, packs, lip balms, etc., makeup cosmetics such as sunscreens, lipsticks, foundations, eye colors, etc., toiletries such as body washes, soaps, shampoos, rinses, conditioners, etc., hair cosmetics such as hair setting agents, etc. The composition of the present invention is suitably used as an anti-aging cosmetic that improves wrinkles and sagging.

[0076] (How to use) When the composition of the present invention is a cosmetic product, it is used by taking an appropriate amount in the palm of one's hand and applying it to the skin. It is recommended to use it as part of morning and evening skin care. [Example]

[0077] The present invention will be specifically explained below based on test examples, but the present invention is not limited to these. Furthermore, blending amounts in the following test examples are expressed as % by mass unless otherwise specified.

[0078] [Test Example 1: Test to inhibit the decrease in the number of adipose stem cells] Adipose stem cell samples were prepared as follows. A human-derived adipose stem cell line (Lifeline Cell Technology) was used. The cells were cultured in StemLife Basal Medium (Lifeline Cell Technology) at 37°C under conditions of 5% carbon dioxide and 95% air. StemLife Basal Medium supplemented with MSC LifeFactor (Lifeline Cell Technology) was used for culture.

[0079] Adipose stem cells (1.0×10 4Cells / ml) were seeded into each well of a Corning® CellBIND® 96-well, clear, flat-bottom polystyrene microplate (Corning). 1500 μg / ml of 7β-hydroxycholesterol (Sigma-Aldrich) was added (Comparative Example 1), or 1500 μg / ml of 7β-hydroxycholesterol, 100 μM of pyrroloquinoline quinone disodium salt (Bio PQQ, Mitsubishi Gas Chemical Company), and 0.001% of evening primrose seed extract (Luna White B, Ichimaru Pharcos) (0.00001% content in the composition as evening primrose seed extract) were added (Example 1). Culture was performed for 48 hours at 37°C under conditions of 5% carbon dioxide and 95% air. A control was prepared using normal medium without the test substance. Thereafter, absorbance was measured using Cell Counting Kit-8 (wst-8) REF: 343-07623, and the cell viability of each test example was calculated, with the viability of the control adipose stem cells set at 100.

[0080] The results are shown in Table 1 below.

[0081] [Table 1]

[0082] As shown in Table 1, while 7β-hydroxycholesterol alone reduced the viability of adipose stem cells, the addition of pyrroloquinoline quinone disodium salt and evening primrose extract inhibited the decrease in adipose stem cell number caused by 7β-hydroxycholesterol. These results demonstrate that fatigue mediators produced by various tissues in the body affect the decrease in adipose stem cell number, i.e., the decrease in adipose tissue. Therefore, it has become clear that the use of an adipose tissue decrease inhibitor can inhibit the decrease in adipose stem cell number caused by fatigue mediators and significantly reduce skin sagging.

[0083] [Test Example 2: Skin sagging prevention test] Twenty-three female subjects, aged between their late 40s and 60s, who reported feeling fatigued in their daily lives, were given a test product containing pyrroloquinoline quinone disodium salt (0.01-0.1% by weight) and evening primrose extract (evening primrose seed extract content in the composition: 0.000001-0.0001% by weight), which was applied to the entire face twice daily, morning and evening. A VAS questionnaire was administered at the start of continuous use and after 4 and 8 weeks of continuous use to assess improvement in skin texture, firmness and elasticity, wrinkles, nasolabial folds, sagging, pores, and facial impression. Skin images were also taken using VISIA®-CRP, VECTRA Handy, ANTERA 3D, and other devices.

[0084] The results are shown in Table 2 below. The table shows the percentage of subjects who showed improvement in each item using the VAS method after 4 or 8 weeks of continuous use.

[0085] [Table 2]

[0086] As described above, there was a significant improvement in items such as skin sagging, suggesting that the use of the fat layer reduction inhibitor can suppress the decline in the number of adipose stem cells caused by fatigue transmitters, thereby improving skin sagging caused by fatigue.

[0087] Furthermore, Table 3 below shows the changes in facial images of six representatives of the 23 female subjects at the start of continuous use of the test product and after eight weeks of continuous use, as well as comments from the subjects regarding their subjective symptoms.

[0088] [Table 3]

[0089] As can be seen from the images above, it can be seen that the fine lines around the eyes and beside the nose, nasolabial folds (wrinkles that extend in an eight-shape from the sides of the nose to both ends of the lips, also known as nasolabial folds), and marionette lines (wrinkles that extend downward from the corners of the mouth towards the chin) have become shallower, suggesting that the use of a fat layer reduction inhibitor can inhibit the decline in the number of fat stem cells caused by fatigue transmitters, thereby improving sagging skin.

Claims

1. A composition for inhibiting sagging skin caused by fatigue, comprising an agent for inhibiting fat layer reduction.

2. 2. The composition for preventing sagging skin due to fatigue according to claim 1, wherein the decrease in the fat layer is due to a decrease in the number of adipose stem cells.

3. The composition for preventing skin sagging due to fatigue according to claim 2, wherein the decrease in the number of adipose stem cells is due to fatigue mediators.

4. 4. The composition for suppressing skin sagging due to fatigue according to claim 3, wherein the fatigue transmitter is 7β hydroxycholesterol.

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