Autophagy inducers

Abstract

To provide useful agents for inducing autophagy.SOLUTION: The agent is composed of a quercetin glycoside or a safflower component (safflower extract, and the like).SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an agent that is useful for inducing autophagy, etc. [Background technology]

[0002] Autophagy is a cellular metabolic function that serves to degrade unnecessary proteins and organelles within cells.

[0003] Thus, components effective in inducing such autophagy are being sought. For example, Patent Document 1 discloses an autophagy inducer containing cyclic glucooligosaccharide as an active ingredient. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] International Publication No. 2018-173653 Brochure Summary of the Invention [Problem to be solved by the invention]

[0005] An object of the present invention is to provide a novel agent that is useful for inducing autophagy, etc. [Means for solving the problem]

[0006] As a result of intensive research into achieving the above-mentioned objectives, the inventors have discovered that quercetin glycosides (in particular, glycosides containing quercetin-7-glucoside) and safflower extract are useful for inducing (improving, enhancing, expressing) autophagy and for anti-aging (e.g., preventing and improving skin aging), and have thus completed the present invention.

[0007] That is, the present invention relates to the following inventions, etc. [1] Contains quercetin glycoside (as an active ingredient) and is an autophagy inducer (autophagy activator, autophagy expresser). [2] Contains quercetin glycoside (as an active ingredient), an anti-aging agent. [3] Contains safflower ingredients (as active ingredients) and is an autophagy inducer (autophagy activator, autophagy expresser). [4] Contains safflower ingredients (as an active ingredient), an anti-aging agent. [5] The agent described in [3] or [4], wherein the safflower component is a safflower extract containing quercetin glycoside. [6] The agent according to any one of [1] to [5], wherein the quercetin glycoside or safflower component contains quercetin-7-glucoside. [7] The agent according to any one of [3] to [6], wherein the safflower component is a safflower extract containing at least safflower leaves. [8] The agent according to any one of [3] to [7], wherein the safflower component is a safflower extract (extract) in a solvent containing at least alcohol (such as ethanol). [9] The agent according to any one of [3] to [8], wherein the safflower component contains quercetin-7-glucoside in an amount of 0.03% by mass or more.

[10] The agent according to any one of [1] to [9], which is used for preventing and / or improving skin aging.

[11] A composition comprising the agent (quercetin glycoside, safflower component) according to any one of [1] to

[10] .

[12] The composition described in

[11] , which is used for preventing and / or improving skin aging.

[13] The composition according to

[11] or

[12] , containing quercetin-7-glucoside in an amount of 0.00003% by mass or more.

[14] The composition according to any one of

[11] to

[13] , which is for use in cosmetics.

[15] The agent or composition according to any one of [1] to

[14] , for inducing autophagy in epidermal keratinocytes and / or fibroblasts. Effect of the Invention

[0008] According to the present invention, it is possible to provide a novel agent and the like that is useful for inducing autophagy. [Brief description of the drawings]

[0009] [Figure 1] FIG. 1 is a diagram (graph) showing the results obtained in Example 1. [Diagram 2] FIG. 2 is a graph showing the results obtained in Example 2. [Diagram 3] FIG. 3 is a graph showing the results obtained in Example 3. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] [Agent] (First aspect) In a first aspect of the present invention, an agent containing (containing as an active ingredient) a quercetin glycoside (a glycoside of quercetin) is provided.

[0011] Quercetin is the compound shown below, and quercetin glycoside is a compound in which a sugar is substituted (bonded) to the hydroxyl group of quercetin (this compound).

[0012] [ka]

[0013] In the quercetin glycoside, the sugar is not particularly limited, and may be, for example, a monosaccharide (monosaccharides), an oligosaccharide, a polysaccharide (polysaccharides), etc. The sugar (oligosaccharide or polysaccharide) may be either a homopolysaccharide or a heteropolysaccharide.

[0014] The number of carbon atoms in the monosaccharide is not particularly limited, and the monosaccharide may be, for example, a pentose or a hexose. The monosaccharide may also be, for example, a furanose or a pyranose.

[0015] Specific sugars include monosaccharides [e.g., pentoses (e.g., ribose, arabinose, xylose, deoxyribose, etc.), hexoses (e.g., fructose, tagatose, allose, altrose, glucose, mannose, galactose, rhamnose, glucosamine, galactosamine, glucuronic acid), etc.], and oligosaccharides or polysaccharides formed by combining these monosaccharides [e.g., disaccharides (e.g., maltose, kojibiose, cellobiose, isomaltose, gentibiose, lactose, rutinose, neohesperidose, etc.)], etc.

[0016] Among these, representative sugars include monosaccharides (for example, hexoses such as glucose and galactose).

[0017] The sugar may be in the D-form, the L-form, or a mixture thereof.

[0018] In quercetin glycosides, the substitution (bond) position of the sugar is not particularly limited and may be any of the hydroxyl groups of quercetin. In addition, the number of sugars (quercetin or hydroxyl groups of quercetin) [substitution (bond) number] in quercetin glycosides is also not particularly limited and may be 1 or 2 or more (e.g., 2 to 5, 2 to 4, 2 to 3, 2, etc.).

[0019] When the number of sugars is two or more, the sugars may be the same or different.

[0020] In addition, the quercetin glycoside may be any of the α-form (α anomer, α-glycoside (O-glycoside)), the β-form (β anomer, β-glycoside (O-glycoside)), or a mixture thereof.

[0021] Specific examples of quercetin glycosides include quercetin glucoside (e.g., quercetin-3-glucoside, quercetin-7-glucoside), quercetin galactoside (e.g., quercetin-3-galactoside), quercetin rhamnoside (e.g., quercetin-3-rhamnoside), quercetin glucuronide (e.g., quercetin-3-glucuronide), and quercetin rutinoside (e.g., quercetin-3-rutinoside).

[0022] The quercetin glycosides may be used alone or in combination of two or more kinds.

[0023] Among these, quercetin glucoside and / or quercetin-7-glycoside are preferred, and quercetin-7-glucoside is particularly preferred, and therefore the quercetin glycoside may contain at least such a glycoside (e.g., quercetin-7-glucoside).

[0024] In such cases, the quercetin glycoside may contain quercetin glucoside and / or quercetin-7-glycoside in a proportion of, for example, 10% by mass or more, 30% by mass or more, 50% by mass or more, 60% by mass or more, 70% by mass or more, 80% by mass or more, 90% by mass or more, relative to the total quercetin glycoside, or may contain substantially 100% by mass.

[0025] In particular, when the quercetin glycoside contains quercetin-7-glucoside, the proportion of quercetin-7-glucoside relative to the total quercetin glycoside may be, for example, 1% by mass or more (e.g., 5% by mass or more), preferably 10% by mass or more (e.g., 15% by mass or more), more preferably 20% by mass or more, and particularly 30% by mass or more.

[0026] The quercetin glycoside may be a commercially available product or may be one synthesized by a conventional method, or may be derived from a plant (the plant itself or a product separated or extracted from a plant) like the safflower component described below.

[0027] (Second aspect) In a second aspect of the present invention, there is provided an agent containing a safflower component (containing the safflower component as an active ingredient). Examples of safflower components include safflower, safflower extract, etc., and these may be used in combination. As the safflower component, safflower extract is typically used in many cases.

[0028] As the safflower, for example, parts such as flowers, leaves, seeds (seeds and seed coats), stems and roots may be used, or a combination of these may be used, or the whole plant may be used.

[0029] As safflower, in particular safflower including at least the leaves may be used.

[0030] The safflower extract may be a commercially available product, or may be obtained by subjecting safflower to an extraction process.

[0031] In the extraction, the solvent (extraction solvent) can be selected depending on the part of the safflower to be used, and examples of the solvent include water, alcohols [e.g., alkanols (e.g., C solubility oils such as methanol, ethanol, isopropanol, n-butanol, etc.], 1-4 alkanols), polyols (e.g., ethylene glycol, propylene glycol, 1,3-butylene glycol, glycerin, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), ethers (e.g., diethyl ether, etc.), esters (e.g., ethyl acetate, etc.), etc. The extraction solvents may be used alone or in combination of two or more kinds.

[0032] Representative extraction solvents include water, alcohols (such as ethanol), and mixtures thereof.

[0033] In particular, the solvent may be a solvent containing at least a polar solvent (e.g., alcohols), particularly a solvent containing ethanol (e.g., a solvent containing ethanol at 30% by mass or more, preferably 50% by mass or more, and more preferably 70% by mass or more (e.g., 90% by mass or more)). By using such a solvent, it is easy to efficiently obtain a safflower extract containing quercetin glycosides (e.g., quercetin-7-glucoside).

[0034] The extraction temperature and extraction time are not particularly limited and can be appropriately selected depending on the extraction solvent and extraction method.

[0035] In addition, when performing the extraction, the safflower may be subjected to an appropriate treatment (such as crushing, heating, or drying) as necessary. The extract may be further subjected to concentration or drying (such as drying at room temperature or freeze-drying).

[0036] The form of the safflower component is not particularly limited, and may be, for example, a liquid (such as an extract containing an extraction solvent) or a powder (or granular powder).

[0037] The safflower component may particularly contain quercetin glycoside. Such safflower components containing quercetin glycoside can be efficiently obtained by selecting the part of the safflower to be used and, in the case of an extract, the extraction conditions, etc.

[0038] Examples of the quercetin glycoside include the same glycosides as those exemplified in the first embodiment, and preferred embodiments thereof are also the same.

[0039] For example, the safflower component may contain at least quercetin glucoside and / or quercetin-7-glycoside, in particular quercetin-7-glucoside.

[0040] The safflower component containing quercetin glycoside may contain other components (components other than quercetin glycoside). Such other components may include, for example, quercetin, luteolin, luteolin glycoside (e.g., luteolin-7-glucoside), etc., depending on the part of the safflower and the extraction conditions.

[0041] The other ingredients may be contained in the safflower ingredient either alone or in combination of two or more.

[0042] When a safflower component (e.g., safflower extract) contains quercetin glycoside, the proportion of quercetin glycoside in the safflower component (proportion to the total solids content when a solvent is included) may be, for example, 0.01 mass% or more (e.g., 0.03 mass% or more), preferably 0.1 mass% or more (e.g., 0.3 mass% or more), and more preferably 1 mass% or more (e.g., 3 mass% or more). The upper limit of the proportion of quercetin glycoside in the safflower components (proportion to the total solids when a solvent is included) is not particularly limited, but may be, for example, 0.3 mass%, 1 mass%, 3 mass%, 5 mass%, 10 mass%, 20 mass%, 30 mass%, etc.

[0043] When a safflower component (e.g., safflower extract) contains quercetin-7-glucoside, the proportion of quercetin-7-glucoside in the safflower component (proportion to the total solids when a solvent is included) may be, for example, 0.001 mass% or more (e.g., 0.003 mass% or more, 0.005 mass% or more, 0.01 mass% or more), preferably 0.01 mass% or more (e.g., 0.03 mass% or more, 0.05 mass% or more, 0.1 mass% or more), and more preferably 0.1 mass% or more (e.g., 0.3 mass% or more, 0.5 mass% or more, 1 mass% or more). The upper limit of the proportion of quercetin-7-glucoside in the safflower components (proportion relative to the total solids content when a solvent is included) is not particularly limited, but may be, for example, 0.1 mass%, 1 mass%, 3 mass%, 5 mass%, 10 mass%, etc.

[0044] When a safflower component (e.g., safflower extract) contains luteolin-7-glucoside, the proportion of luteolin-7-glucoside in the safflower component (proportion to the total solids when a solvent is included) may be, for example, 0.01 mass% or more, preferably 0.1 mass% or more, and more preferably 1 mass% or more. The upper limit of the proportion of luteolin-7-glucoside in the safflower components (proportion relative to the total solids content when a solvent is included) is not particularly limited, but may be, for example, 0.1 mass%, 1 mass%, 3 mass%, 5 mass%, 10 mass%, etc.

[0045] (Application of the agent) The agents of the present invention (the agent of the first embodiment and the agent of the second embodiment) can be used for specific purposes.

[0046] First, the agent of the present invention can be used as an autophagy inducer [agent for inducing (expressing, improving, enhancing, activating) autophagy]. As described above, autophagy (function) plays a role in, for example, breaking down unnecessary proteins and organelles within cells, and the agent of the present invention can induce (express, improve, enhance, activate) such autophagy (function). Such an agent may induce autophagy in skin cells. Examples of skin cells include epidermal keratinocytes, fibroblasts, and the like. In particular, the agent of the present invention can induce autophagy in epidermal keratinocytes and fibroblasts, and can efficiently exert the autophagy function (and the associated skin prevention or improvement function).

[0047] The agent of the present invention can also be used as an anti-aging agent.

[0048] In particular, the agent of the present invention may be an agent for preventing and / or improving skin aging.

[0049] In addition, in anti-aging agents (and further agents for preventing and / or improving skin aging), the anti-aging effect / function (and further the effect / function of preventing and / or improving skin aging) may be accompanied by the induction of autophagy (function).

[0050] The agent of the present invention may also be used as an agent for a specific application, for example, for medicine, food and beverage, cosmetics, etc.

[0051] [Composition] The present invention also includes a composition comprising the agent (the first or second embodiment).

[0052] Such compositions can also be used for the same functions and uses as the above-mentioned agents. For example, they can be used for autophagy induction, anti-aging, and prevention and / or improvement of skin aging. They can also be used for medicines, foods and beverages, cosmetics, etc.

[0053] In particular, the composition of the present invention may be suitably used as a cosmetic (composition for cosmetic use) from the viewpoint of having an autophagy-inducing effect and an anti-aging effect. The composition for cosmetic use is not particularly limited, and may be classified as a quasi-drug, such as medicated cosmetics, according to the definition of the Pharmaceutical Affairs Law.

[0054] The composition of the present invention only needs to contain the above-mentioned agent (quercetin glycoside or safflower component), and may contain other ingredients depending on the intended use, form, etc.

[0055] Such other components include bases or carriers, additives, other active ingredients, etc. Such other components and their ratios can be appropriately selected depending on the form, properties, etc. of the composition.

[0056] The base or carrier is not particularly limited, but examples thereof include hydrocarbons such as paraffin, liquid paraffin, squalane, white wax, gelling hydrocarbons (such as Plastibase), ozokerite, ceresin, petrolatum, hard fat, microcrystalline wax, α-olefin oligomers, and light liquid paraffin; fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, and isostearic acid; glyceryl tri-2-ethylhexanoate (trioctanoin), tri(caprylic acid / capric acid)glyceryl; triglycerides such as glyceryl triglyceride; higher alcohols such as cetanol, stearyl alcohol, and behenyl alcohol; methylpolysiloxane, highly polymerized methylpolysiloxane, dimethylsiloxane-methyl(polyoxyethylene)siloxane-methyl(polyoxypropylene)siloxane copolymer, dimethylsiloxane-methyl(polyoxyethylene)siloxane copolymer, dimethylsiloxane-methyl(polyoxypropylene)siloxane copolymer, polyoxyethylene-methylpolysiloxane copolymer, poly(oxyethylene-oxypropylene)-methylpolysiloxane copolymer, dimethylsiloxane-methylcetyloxysiloxane copolymer, dimethylsiloxane-methylstearoxysiloxane copolymer, alkyl acrylate copolymer methylpolysiloxane ester, crosslinked methylpolysiloxane, crosslinked methylphenylpolysiloxane, crosslinked polyether modified silicone, crosslinked alkylpolyether modified silicone, crosslinked alkyl modified silicone, decamethylcyclopentasiloxane, ethyltrisiloxane, methyl Silicone oils such as ethyl trimethicone, methylsiloxane network polymer, polyoxyethylene-methylpolysiloxane copolymer, methylhydrogenpolysiloxane, triethoxysilylethyl polydimethylsiloxyethylhexyl dimethicone, and dimethylpolysiloxane; glycol acetates such as ethylene glycol monoacetate, ethylene glycol diacetate, triethylene glycol diacetate, hexylene glycol diacetate, and 2-methyl-2-propene-1,1-diol diacetate;Glycol esters such as triethylene glycol divalerate, 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate, and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate; glycol acrylates such as ethylene glycol diacrylate, diethylene glycol diacrylate, propylene glycol monoacrylate, 2,2-dimethyl-trimethylene glycol diacrylate, and 1,3-butylene glycol diacrylate; glycol dinitrates such as ethylene glycol dinitrate, diethylene glycol dinitrate, triethylene glycol dinitrate, and propylene glycol dinitrate; 2,2'-[1,4-phenylenedioxy]diethanol; cellulose derivatives such as ethyl cellulose, hydroxypropyl cellulose, and hydroxypropyl methyl cellulose; polyvinylpyrrolidone; carrageenan; polyvinyl butyrate; polyethylene glycol dioxane; butylene glycol adipic acid polyester; esters such as isopropyl myristate, octyldodecyl myristate, isopropyl palmitate, cetyl palmitate, isononyl isononanoate, and pentaerythritol tetra 2-ethylhexanoate; polysaccharides such as dextrin and maltodextrin; lower alcohols such as ethanol and isopropanol; 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 aqueous bases such as water. These bases or carriers can be used alone or in combination of two or more.

[0057] The additives are not particularly limited, but examples thereof include antioxidants, surfactants, thickeners, preservatives, pH adjusters, stabilizers, antiseptics, colorants, and fragrances. These additives may be used alone or in combination of two or more.

[0058] Examples of the antioxidant include dibutylhydroxytoluene, butylhydroxyanisole, sorbic acid, sodium sulfite, ascorbic acid, ascorbic acid derivatives (such as ascorbic acid phosphate), tocopherol, tocopherol derivatives, erythorbic acid, and L-cysteine ​​hydrochloride.

[0059] Examples of surfactants 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; glycerin alkyl ethers; alkyl glucosides; amines such as stearylamine and oleylamine; and silicone-based surfactants such as polyoxyethylene-methylpolysiloxane copolymer, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, and PEG-9 polydimethylsiloxyethyl dimethicone.

[0060] Examples of thickeners include guar gum, locust bean gum, carrageenan, xanthan gum, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, acrylates / alkyl methacrylate copolymers, polyethylene glycol, bentonite, alginic acid, macrogol, and cellulose-based thickeners (methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, carboxyethyl cellulose, etc.) and salts thereof.

[0061] Examples of preservatives and antiseptics include benzoic acid, sodium benzoate, dehydroacetic acid, sodium dehydroacetate, isobutyl parahydroxybenzoate, isopropyl parahydroxybenzoate, butyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, benzyl parahydroxybenzoate, methyl parahydroxybenzoate, phenoxyethanol, benzyl alcohol, chlorobutanol, sorbic acid and its salts, chlorhexidine gluconate, alkanediols, and glycerin fatty acid esters.

[0062] Examples of pH adjusters include inorganic acids (hydrochloric acid, sulfuric acid, etc.), organic acids (lactic acid, sodium lactate, citric acid, sodium citrate, succinic acid, sodium succinate, etc.), inorganic bases (potassium hydroxide, sodium hydroxide, etc.), and organic bases (triethanolamine, diisopropanolamine, triisopropanolamine, etc.).

[0063] Examples of the stabilizer include sodium polyacrylate, dibutylhydroxytoluene, butylhydroxyanisole, and edetate.

[0064] Other active ingredients are not particularly limited, but examples thereof include moisturizing ingredients, anti-inflammatory ingredients, antibacterial or germicidal ingredients, vitamins, peptides or derivatives thereof (esters, amides, etc.), cell activating ingredients, anti-aging ingredients, blood circulation promoting ingredients, keratin softening ingredients, whitening ingredients, astringent ingredients, etc. These active ingredients may be used alone or in combination of two or more.

[0065] Examples of moisturizing components include polymeric compounds such as collagen, elastin, keratin, chitin, and chitosan; natural moisturizing factors such as sodium lactate, urea, and sodium pyrrolidone carboxylate; lipids such as ceramide, cholesterol, and phospholipids; and plant extracts such as chamomile extract, witch hazel extract, tea extract, and perilla extract.

[0066] Anti-inflammatory components include, for example, components derived from plants (eg, comfrey), allantoin, glycyrrhizic acid or a derivative thereof, zinc oxide, pyridoxine hydrochloride, tocopherol acetate, salicylic acid or a derivative thereof, ε-aminocaproic acid, and the like.

[0067] Examples of antibacterial or bactericidal components include ethanol, chlorhexidine, salicylic acid, benzalkonium chloride, acrinol, sulfur, resorcinol, benzethonium chloride, adapalene, benzoyl peroxide, clindamycin, cresol, gluconic acid and its derivatives, povidone-iodine, potassium iodide, iodine, isopropylmethylphenol, triclocarban, triclosan, photosensitizer No. 101, photosensitizer No. 201, paraben, phenoxyethanol, 1,2-pentanediol, alkyldiaminoglycine hydrochloride, chlorhexidine gluconate, and zinc paraphenolsulfonate.

[0068] Examples of vitamins include retinol derivatives such as retinol, retinol acetate, and retinol palmitate, vitamin A such as retinal, retinoic acid, methyl retinoate, ethyl retinoate, retinol retinoic acid, d-δ-tocopheryl retinoate, α-tocopheryl retinoate, and β-tocopheryl retinoate; vitamin E such as dl-α-tocopherol, dl-α-tocopherol acetate, dl-α-tocopherol succinate, and dl-α-tocopherol calcium succinate; and riboflavin. Vitamin B2 such as flavin mononucleotide, flavin adenine dinucleotide, riboflavin butyrate, riboflavin tetrabutyrate, riboflavin sodium 5'-phosphate, and riboflavin tetranicotinate; nicotinic acids such as dl-α-tocopherol nicotinate, benzyl nicotinate, methyl nicotinate, β-butoxyethyl nicotinate, and 1-(4-methylphenyl)ethyl nicotinate; ascorbigen-A, ascorbyl stearate, and palmitic ascorbate. Vitamin C such as L-ascorbyl dipalmitate; Vitamin D such as methylhesperidin, ergocalciferol, cholecalciferol; Vitamin K such as phylloquinone and farnoquinone; gamma-oryzanol, dibenzoylthiamine, 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 Vitamin B1 compounds such as thiamine monophosphate, thiamine diphosphate, thiamine diphosphate hydrochloride, thiamine triphosphate, and thiamine triphosphate monophosphate; Vitamin B6 compounds such as pyridoxine hydrochloride, pyridoxine acetate, pyridoxal hydrochloride, 5'-pyridoxal phosphate, and pyridoxamine hydrochloride; Vitamin B12 compounds such as cyanocobalamin, hydroxocobalamin, and deoxyadenosylcobalamin; folic acids such as folic acid and pteroylglutamic acid; nicotinic acids such as nicotinic acid and nicotinamide;Pantothenic acids such as pantothenic acid, calcium pantothenate, pantothenyl alcohol (panthenol), D-panthesine, D-pantethine, coenzyme A, and pantothenyl ethyl ether; biotins such as biotin and bioticin; ascorbic acid derivatives of vitamin C such as ascorbic acid, sodium ascorbate, dehydroascorbic acid, sodium ascorbyl phosphate, and magnesium ascorbyl phosphate; vitamin-like action factors such as carnitine, ferulic acid, α-lipoic acid, and orotic acid;

[0069] Examples of 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.).

[0070] Examples of cell activation components include vitamins such as retinol, thiamine, riboflavin, pyridoxine hydrochloride, and pantothenic acids; α-hydroxy acids such as glycolic acid and lactic acid; tannins, flavonoids, saponin, allantoin, and photosensitizer No. 301.

[0071] Anti-aging ingredients include pangamic acid, kinetin, ursolic acid, turmeric extract, sphingosine derivatives, silicon, silicic acid, N-methyl-L-serine, mevalonolactone, and the like.

[0072] Examples of blood circulation-promoting ingredients include ingredients derived from plants (e.g., ginseng, angelica, arnica, ginkgo, fennel, emmeisou, Dutch oak, chamomile, Roman chamomile, carrot, gentian, burdock, rice, hawthorn, shiitake mushroom, European hawthorn, European juniper, cnidium rhizome, Swertia japonica, thyme, clove, tangerine peel, angelica tree, peach kernel, spruce, carrot, garlic, butcher's broom, grape, peony, horse chestnut, melissa, yuzu, coix seed, rosemary, rose hip, peach, apricot, walnut, corn); glucosyl hesperidin, etc.

[0073] Examples of keratin softening ingredients include salicylic acid, glycolic acid, fruit acid, phytic acid, sulfur, and the like.

[0074] Examples of whitening ingredients include ascorbic acid and its derivatives (phosphate esters, etc.), arbutin, tocopherol, and the like.

[0075] Examples of astringent ingredients include zinc paraphenolsulfonate, zinc oxide, menthol, and ethanol.

[0076] The form of the composition of the present invention is not particularly limited and can be appropriately selected depending on the application, etc. Examples of the form include liquid, fluid, semi-solid, etc. The form of the composition of the present invention (cosmetic composition, etc.) is not particularly limited, and examples thereof include liquids, suspensions, emulsions, creams, ointments, gels, liniments, lotions, aerosols, sheets in which nonwoven fabric is impregnated with a drug solution, etc. Among these, preferred are liquids, suspensions, emulsions, creams, etc.

[0077] Specific uses of the composition of the present invention are not particularly limited, but examples thereof include basic cosmetics such as lotions, cosmetic milky lotions, cosmetic oils, gels, creams, beauty serums, sunscreen cosmetics, packs, masks, hand creams, body lotions, and body creams; cleansing cosmetics such as facial cleansers, makeup removers, body shampoos, shampoos, rinses, and treatments; makeup cosmetics such as makeup bases, foundations, face powders, water-based powders, powders, grease guns, eye shadow bases, eye shadows, nose shadows, lip pencils, lipsticks, lip glosses, blushers, and various colors; hair care products such as shampoos, dry shampoos, conditioners, rinses, rinse-in shampoos, treatments, hair tonics, hair styling products, hair oils, pomades, and hair coloring agents; dentifrices, lip balms, soaps, and body soaps. Among these, preferred are lotions, cosmetic emulsions, cosmetic oils, gels, creams, beauty essences, sunscreen cosmetics, etc., and more preferred are lotions, cosmetic emulsions, creams, beauty essences, etc.

[0078] Specific uses of the composition of the present invention when it is a quasi-drug are not particularly limited, and examples thereof include medicated cosmetics, medicated soaps, medicated dentifrices, antiperspirants, medicated creams, hair restorers, hair dyes, mouthwashes, energy drinks, mouth fresheners, contact lens wearers, germicides, antiseptics, chilblains, digestive aids, herbal medicine-containing health medicines, vitamin-containing health medicines, bath additives, etc. Among these, medicated cosmetics, medicated creams, hair restorers, etc. are preferred.

[0079] The method for producing the composition of the present invention is not particularly limited as long as it uses the agent of the present invention (quercetin glycoside, safflower component), and any conventionally known method can be used depending on the application and properties of the composition. For example, the composition can be produced by adding the agent of the present invention as it is or after emulsification, solubilization or dispersion during production of the composition by a conventional method.

[0080] In the composition of the present invention, the proportion of the agent of the present invention can be appropriately selected depending on the type of composition, the blended ingredients, etc., and is not particularly limited. For example, the proportion of quercetin glycoside (proportion relative to the total solid content when a solvent is included) may be, for example, 0.00003 mass% or more, preferably 0.0003 mass% or more, and more preferably 0.003 mass% or more. The upper limit of the proportion of quercetin glycoside in the composition (proportion relative to the total solids content when a solvent is included) is not particularly limited, and may be, for example, 0.0001 mass%, 0.0003 mass%, 0.001 mass%, 0.003 mass%, 0.01 mass%, 0.03 mass%, etc.

[0081] When the composition of the present invention contains quercetin-7-glucoside, the proportion of quercetin-7-glucoside in the composition (proportion relative to the total solids when a solvent is included) may be, for example, 0.00001 mass% or more, preferably 0.0001 mass% or more, and more preferably 0.001 mass% or more. The upper limit of the proportion of quercetin-7-glucoside in the composition (proportion relative to the total solids content when a solvent is included) is not particularly limited, and may be, for example, 0.0001 mass%, 0.0003 mass%, 0.001 mass%, 0.003 mass%, 0.01 mass%, 0.03 mass%, etc.

[0082] Furthermore, when the composition of the present invention contains a safflower component (e.g., safflower extract), the proportion of the safflower component in the composition (the proportion relative to the total solids when a solvent is included) may be, for example, 0.01 mass% or more, preferably 0.1 mass% or more, and more preferably 1 mass% or more. The upper limit of the proportion of safflower components in the composition (proportion relative to the total solids content when a solvent is included) is not particularly limited, but may be, for example, 0.1 mass %, 1 mass %, 10 mass %, etc.

[0083] [How to use, etc.] The present invention includes various methods using the agent or composition. Such a method may be, for example, a method of using the agent or composition on a subject of use (application).

[0084] Such a method may involve the above-mentioned functions and actions (for example, induction of autophagy, anti-aging, prevention and / or improvement of skin aging).

[0085] The method of using (applying) the agent or composition of the present invention is not particularly limited and can be appropriately selected depending on the subject of use (application), etc. For example, when used as a cosmetic, etc., the method can be appropriately selected depending on the skin condition, age, sex, etc., and for example, an appropriate amount (e.g., about 0.005 to 0.5 g) may be applied to the skin (painted, sprayed, pasted, etc.) several times a day (e.g., 1 to 5 times a day, preferably 1 to 3 times a day). It can also be applied to any skin, such as the face, neck, hands, feet, fingers, trunk, scalp, etc.

[0086] The amount of the agent or composition of the present invention to be used (applied) is also not particularly limited and may be appropriately changed depending on the type and components of the composition. For example, the amount of quercetin glycoside (particularly quercetin glycoside containing quercetin-7-glucoside) or safflower component to be used (applied) for an adult per day is preferably about 0.001 to 10 mg / cm. 2 (skin area), more preferably about 0.01 to 1 mg / cm 2 (skin area). EXAMPLES

[0087] The present invention will be described in detail below with reference to examples, but the present invention is not limited to these.

[0088] [Quantitative analysis of quercetin-7-glucoside and quercetin glycosides] The samples were analyzed according to a known high performance liquid chromatography (HPLC) method, and the peak area of ​​quercetin-7-glucoside was calculated by comparing it with the peak area of ​​a standard sample. The calculations were also performed in the same manner for quercetin glycosides other than quercetin-7-glucoside.

[0089] Synthesis example (safflower extract) 10 g of safflower leaf powder was suspended in 100 mL of 90% by mass ethanol aqueous solution and stirred at room temperature for 1 hour. The extract was separated by filtration, evaporated under reduced pressure, and then freeze-dried to obtain 1 g of safflower extract.

[0090] Example 1 Human epidermal fibroblasts (derived from a 51-year-old Caucasian woman) (hereafter referred to as NHDF) were seeded onto a 6-well plate and incubated at 37°C in 5% CO in DMEM medium (Thermo Fisher Scientific) supplemented with 10% fetal bovine serum, 1% penicillin-streptomycin, and 1% L-glutamine. 2 The mixture was incubated overnight under Safflower extract was added to the medium at 10 and 100 μg / mL and cultured for 24 hours. At the same time, for autophagy flux analysis, safflower extract was added in the same manner and cultured for 8 hours, after which lysosomal inhibitor chloroquine (CQ) was added at 5 μM and cultured for another 16 hours. After culture, the cells were collected with RIPA buffer (Millipore) and samples for SDS-PAGE were prepared using SDS sample buffer. The amount of LC3-II, a marker protein for autophagy, was measured by Western blotting using an LC3 antibody (Cell Signaling Technology, Inc.) Band intensity was measured using the image analysis software ImageJ. When comparing and quantifying the LC3-II band intensity, GAPDH, which is produced in a constant amount in vivo, was used as an internal standard, and the ratio of the LC3-II band intensity to the GAPDH band intensity was calculated and normalized. In the autophagy flux analysis, if the following two conditions are met: the LC3-II band intensity increases upon treatment with the test substance, and the band intensity further increases upon treatment with a lysosomal inhibitor, the test substance is judged to have an autophagy-inducing effect. The expression level of LC3-II normalized with GAPDH as an internal standard is shown in Figure 1. The expression level of LC3-II in untreated cells was set to "1," and the relative values ​​of various cells were calculated. As shown in Figure 1, the LC3-II band intensity increased in the groups to which 10 and 100 μg / mL safflower extract was added, compared to the control group. Furthermore, a further increase in the band intensity was confirmed by the addition of CQ.

[0091] Example 2 Normal human epidermal keratinocytes (derived from a 47-year-old Caucasian woman) (hereafter referred to as NHEK) were seeded onto a 6-well plate and incubated at 37°C in 5% CO in Epilife medium (Thermo Fisher Scientific) supplemented with human keratinocyte growth factor (HKGS). 2 The mixture was incubated overnight under Safflower extract was added to the medium at 1, 10, and 100 μg / mL and cultured for 24 hours. At the same time, for autophagy flux analysis, safflower extract was added in the same manner and cultured for 8 hours, after which lysosomal inhibitor chloroquine (CQ) was added at 5 μM and cultured for another 16 hours. After culture, the cells were collected with RIPA buffer (Millipore) and samples for SDS-PAGE were prepared using SDS sample buffer. The amount of LC3-II, a marker protein for autophagy, was measured by Western blotting using an LC3 antibody (Cell Signaling Technology). The image analysis software ImageJ was used to measure band intensity. When comparatively quantifying the LC3-II band intensity, GAPDH, which is produced in a constant amount in vivo, was used as an internal standard, and the ratio of the LC3-II band intensity to the GAPDH band intensity was calculated and standardized. The expression level of LC3-II normalized with GAPDH as an internal standard is shown in Figure 2. The expression level of LC3-II in untreated cells was set to "1," and the relative values ​​of various cells were calculated. As shown in Figure 2, the LC3-II band intensity increased in the groups to which 1, 10, and 100 μg / mL safflower extract was added, compared to the control group. In addition, a further increase in the band intensity was confirmed by the addition of CQ.

[0092] Example 3 Human epidermal fibroblasts (neonatal origin) (hereafter referred to as NHDF) were seeded in a 6-well plate and incubated at 37°C and 5% CO in DMEM medium (Thermo Fisher Scientific) supplemented with 10% fetal bovine serum, 1% penicillin-streptomycin, and 1% L-glutamine. 2 The mixture was incubated overnight under Quercetin-7-glucoside was added to the medium at 0.05, 0.5, and 5 μg / mL and cultured for 24 hours. At the same time, safflower extract was added in the same manner for autophagy flux analysis, and the cells were cultured for 8 hours, after which lysosomal inhibitor chloroquine (CQ) was added at 5 μM and cultured for another 16 hours. After culture, the cells were collected with RIPA buffer (Millipore), and samples for SDS-PAGE were prepared using SDS sample buffer. The amount of LC3-II, a marker protein for autophagy, was measured by Western blotting using an LC3 antibody (Cell Signaling Technology). The image analysis software ImageJ was used to measure band intensity. When comparatively quantifying the LC3-II band intensity, GAPDH, which is produced in a constant amount in vivo, was used as an internal standard, and the ratio of the LC3-II band intensity to the GAPDH band intensity was calculated and standardized. The expression level of LC3-II normalized with GAPDH as an internal standard is shown in Figure 3. The expression level of LC3-II in untreated cells was set to "1," and the relative values ​​of various cells were calculated. As shown in Figure 3, the LC3-II band intensity increased in the groups to which 0.05, 0.5, and 5 μg / mL of quercetin-7-glucoside was added compared to the control group. Furthermore, a further increase in the band intensity was confirmed by the addition of CQ.

[0093] Specific formulations of compositions containing the agent of the present invention are exemplified below.

[0094] Formulation example 1: Lotion A lotion having the following composition is prepared according to the following preparation method. The following ingredients are formulated so that the total is 100% by weight. All ingredients are mixed and stirred at room temperature to make a uniform solution, and the pH is adjusted to 5.5 to obtain a lotion. Ingredients Weight% Concentrated glycerin 4.0 Sorbitol 4.0 Sodium citrate 0.3 Polyoxyethylene hydrogenated castor oil 0.5 Safflower Extract 0.1 Ethanol 15.0 Fragrance 0.005 Citric acid (appropriate amount) Purified water remainder

[0095] Formulation example 2: Facial cleansing cream A facial cleansing cream having the following composition is prepared according to the following preparation method. Components A to C are formulated in the following proportions so that the total of components A, B and C is 100% by weight. First, the mixture of component A is heated and dissolved, and maintained at 80°C. Next, the mixture of component B, which has been separately heated and dissolved at 80°C, is added to the mixture of component A and thoroughly stirred. After that, the mixture is cooled with stirring, and the mixture of component C is added at 50°C to obtain a face wash cream. "Component A" Ingredients Weight% Myristic acid 14.0 Stearic acid 12.0 Lauric acid 3.5 Oleyl alcohol 1.5 Coconut oil fatty acid amidopropyl betaine 10.5 "Component B" Ingredients Weight% Concentrated glycerin 18.0 Potassium hydroxide 7.0 Paraoxybenzoic acid ester (appropriate amount) Purified water remainder "Ingredient C" Ingredients Weight% Safflower Extract 0.1 Fragrance (appropriate amount)

[0096] Formulation example 3: Emulsion An emulsion having the following composition is prepared according to the following preparation method. Components D to F are formulated in the following proportions so that the total of components D, E, and F is 100% by weight. First, the component D mixture is heated and dissolved, and maintained at 80°C. Next, the component E mixture, which has been separately heated and dissolved at 80°C, is added to the component D mixture and thoroughly stirred. After that, the mixture is cooled with stirring, and the component F mixture is added at 50°C to obtain an emulsion. "Ingredient D" Ingredients Weight% Sucrose fatty acid ester 1.0 Carboxyvinyl polymer 0.06 Potassium hydroxide 0.028 Paraoxybenzoic acid ester (appropriate amount) Purified water remainder "Ingredient E" Ingredients Weight% Olive oil 4.0 Jojoba Oil 4.0 Myristyl Lactate 2.0 Self-emulsifying glyceryl monostearate 1.5 Lipophilic glyceryl monostearate 1.5 "Component F" Ingredients Weight% Safflower Extract 0.1 Fragrance 0.2 [Industrial Applicability]

[0097] The agent of the present invention can be used as an autophagy inducer or the like.

Claims

1. An autophagy inducer containing quercetin-7-glucoside as an active ingredient.

2. An anti-aging agent containing quercetin-7-glucoside as an active ingredient.

3. An autophagy inducer containing safflower components containing quercetin-7-glucoside as an active ingredient.

4. The agent according to claim 3, wherein the safflower component is a safflower extract containing quercetin-7-glucoside in a proportion of 0.001% by mass or more.

5. The agent according to claim 3 or 4, wherein the safflower component is a safflower extract containing at least safflower leaves.

6. The agent according to any one of claims 3 to 5, wherein the safflower component is a safflower extract in a solvent containing at least alcohol.

7. The agent according to any one of claims 3 to 6, wherein the safflower component contains quercetin-7-glucoside in an amount of 0.03% by mass or more.

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