Novel compound and use thereof

Abstract

To provide a novel compound isolated from rice bran extract and a use thereof.SOLUTION: The present invention provides a compound represented by chemical formula (1), an immunoactivator comprising the compound of chemical formula (1), and a humectant comprising the compound of chemical formula (1).SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a novel compound and its use. This invention is widely used in medicines, quasi-drugs, foods (including health foods, functional foods, and foods with specified health uses), cosmetics, skin care products, etc. [Background technology]

[0002] The active ingredients contained in rice-derived ceramide compositions are β-sitosterol-3-O-glucoside (BSG) and elasticamide, which are known to improve transepidermal water loss (TEWL) in a 3D human epidermis model.

[0003] Macrophages also have stronger phagocytic ability than neutrophils. By phagocytosis, they release antigen-presenting and inflammatory cytokines, which act on other cells and strengthen the immune response. There are various inflammatory cytokines, but it is known that IL-6, TNF-α, etc. activate dendritic cells when stimulated with LPS, and can be used as immunostimulants. DISCLOSURE OF THEINVENTION [Problem to be solved by the invention]

[0004] Against this background, the inventor discovered that rice bran extract contains a new compound and that this compound has moisturizing and immunostimulating effects, thus completing the present invention. That is, the present invention provides a novel compound and its use. [Means for solving the problem]

[0005] The features of the present invention for solving the above problems are as follows. 1. A compound represented by the following chemical formula (1). [ka] 2. An immunostimulant containing the compound shown in 1 above as an active ingredient. 3. A moisturizer containing the compound shown in 1 above as an active ingredient. 4. A method for producing the compound described in 1 above, comprising a step of isolating compound A from an extract of rice bran. Effect of the Invention

[0006] The compound of the present invention (hereinafter referred to as "Compound A") has an immunostimulating effect and a TEWL reducing effect, as described below. This allows it to be used in medicines, quasi-drugs, foods (including health foods, functional foods, and foods for specified health uses), cosmetics, skin care products, etc. In addition, it was found that the above-mentioned compound A has an effect of promoting IL-6 gene expression in macrophages. As a result, compound A has an effect of activating natural immunity and stimulating immunity. For these reasons, it is useful as an immunostimulant. Furthermore, the compound A has a TEWL-reducing effect, which makes the compound A useful as a moisturizing agent. Furthermore, since the above-mentioned compound A has been found to be contained in rice bran, it can be obtained by isolating compound A from an extract of rice bran. [Brief description of the drawings]

[0007] [Figure 1] FIG. 2 shows proton-carbon correlations (arrows) and proton-proton correlations (thick lines) of compound A. [Diagram 2] 1 is a graph showing the effect of compound A on the TEWL of a human epidermis 3D model. [Diagram 3] 1 is a graph showing the gene expression level of IL-6 in macrophage-derived cells (Raw264.7). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0008] The present invention will now be described in detail. The present invention relates to compound A represented by the following chemical formula (1). [ka]

[0009] The method for obtaining compound A is not particularly limited, but for example, a method for isolating compound A from an extract of rice bran is preferable because it contains compound A at a high concentration. The "rice bran extract" is not particularly limited as long as it is produced during the process of manufacturing rice bran oil. For example, the rice bran extract can be obtained by extracting rice bran with an organic solvent and then precipitating the extract, but is not limited to this method. Also, the rice bran extract may be a by-product produced in the manufacturing process from rice bran oil.

[0010] Here, the method for isolating compound A from the extract is not particularly limited, but it can be isolated, for example, by chromatography using activated clay, activated carbon, silica gel, alumina, diatomaceous earth, synthetic adsorbents, ion exchange resins, etc., or by a method of removing components other than compound A by adsorption, decomposition, precipitation, filtration, dissolution, distillation, etc. After that, appropriate purification may be carried out by HPLC or the like. Specifically, it can be produced according to the examples of the present specification.

[0011] The above-mentioned compound A of the present invention can be used as a TEWL lowering agent.

[0012] Furthermore, the above compound A can be used as an immunostimulant.

[0013] Compound A of the present invention can be used as a material for various foods and beverages (including health foods, functional foods, foods with specified health uses, etc.). Examples of foods and beverages include general foods such as confectionery (gum, candy, caramel, chocolate, cookies, snacks, jellies, gummies, tablets, etc.), noodles (soba, udon, ramen, etc.), dairy products (milk, ice cream, yogurt, etc.), seasonings (miso, soy sauce, etc.), soups, beverages (juice, coffee, black tea, tea, carbonated drinks, sports drinks, etc.), health foods (tablets, capsules, etc.), nutritional supplements (nutritional drinks, etc.), foods with specified health uses, and foods with functional uses. The agent of the present invention may be appropriately mixed into these foods and beverages. Compound A may be added as it is, or may be used as a composition containing enough compound A to be used as an active ingredient, such as a plant extract, particularly preferably a rice bran extract. In this case, the content of compound A contained in the rice bran extract is not particularly limited as long as it is an amount contained as an active ingredient, but it is preferable to use one containing, for example, 0.01 to 1 wt%, or even 0.05 to 0.5 wt%.

[0014] These foods and beverages can contain a variety of ingredients depending on their type, for example, the following food ingredients can be used: glucose, fructose, sucrose, maltose, sorbitol, stevioside, corn syrup, lactose, citric acid, tartaric acid, malic acid, succinic acid, lactic acid, L-ascorbic acid, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid esters, polyglycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, propylene glycol fatty acid esters, gum arabic, carrageenan, casein, gelatin, pectin, agar, B vitamins, nicotinamide, calcium pantothenate, amino acids, calcium salts, colorants, flavorings, and preservatives.

[0015] As a specific manufacturing method, the agent of the present invention can be easily incorporated into food and beverages (instant foods, etc.) by spray-drying or freeze-drying the agent together with powdered cellulose and forming it into a powder, granules, tablets, or solution. The agent of the present invention can also be dissolved in, for example, fats and oils, ethanol, glycerin, or a mixture of these to form a liquid, which can then be added to beverages or solid foods. If necessary, it can also be mixed with a binder such as gum arabic or dextrin to form a powder or granules, which can then be added to beverages or solid foods.

[0016] The compound A of the present invention may be used as a material for medicines (including pharmaceuticals and quasi-drugs). The medicines can be produced by appropriately mixing the agent of the present invention with raw materials for pharmaceutical preparations. Examples of pharmaceutical raw materials that can be incorporated into the agent of the present invention include excipients (glucose, lactose, sucrose, sodium chloride, starch, calcium carbonate, kaolin, crystalline cellulose, cocoa butter, hardened vegetable oil, kaolin, talc, etc.), binders (distilled water, saline, ethanol water, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethylcellulose, potassium phosphate, polyvinylpyrrolidone, etc.), disintegrants (sodium alginate, agar, sodium bicarbonate, calcium carbonate, sodium lauryl sulfate, stearate monoglyceride, starch, lactose, powdered gum arabic, gelatin, ethanol, etc.), disintegration inhibitors (sucrose, stearin, cocoa butter, hydrogenated oil, etc.), absorption enhancers (quaternary ammonium bases, sodium lauryl sulfate, etc.), adsorbents (glycerin, starch, lactose, kaolin, bentonite, silicic acid, etc.), lubricants (purified talc, stearates, polyethylene glycol, etc.), etc. Compound A may be added as it is, or may be used as a composition, such as a plant extract, particularly preferably a rice bran extract, that contains a sufficient amount of compound A to be able to use it as an active ingredient. In this case, the content of compound A contained in the rice bran extract is not particularly limited as long as it is an amount that is contained as an active ingredient, but it is preferable to use one that contains 0.01 to 1 wt%, or even 0.05 to 0.5 wt%.

[0017] The method of administration of compound A of the present invention can be generally orally administered in the form of tablets, pills, soft or hard capsules, fine granules, powders, granules, liquids, etc., but may also be parenterally administered. When administered parenterally, it can be administered in the form of a solution or with the addition of a dispersant, suspending agent, stabilizer, etc., by local tissue administration, intradermal, subcutaneous, intramuscular, or intravenous injection. It may also be in the form of a suppository, etc. Furthermore, it can be administered as eye drops. Compound A may be added as it is, or may be used as a composition containing compound A sufficiently to be able to be used as an active ingredient, such as a plant extract, particularly preferably a rice bran extract. In this case, the content of compound A contained in the rice bran extract is not particularly limited as long as it is the amount contained as an active ingredient, but it is preferable to use one containing 0.01 to 1 wt%, or more preferably 0.05 to 0.5 wt%.

[0018] The dosage may vary depending on the method of administration, the condition, the patient's age, etc., but adults can usually be given 0.5 to 5,000 mg of active ingredient per day, and children can usually be given 0.5 to 3,000 mg. The compounding ratio of compound A can be appropriately changed depending on the dosage form, but it is usually about 0.001 to 1.0 wt% when administered orally or via mucosal absorption, and about 0.0001 to 1.0 wt% when administered parenterally. Note that the dosage varies depending on various conditions, so in some cases a smaller dosage than the above is sufficient, and in other cases it is necessary to administer more than the range. Compound A may be added as it is, or may be used as a composition, such as a plant extract, particularly preferably a rice bran extract, that contains a sufficient amount of compound A to be used as an active ingredient. In this case, the content of compound A contained in the rice bran extract is not particularly limited as long as it is an amount that is contained as an active ingredient, but it is preferable to use one that contains, for example, 0.01 to 1 wt%, or even 0.05 to 0.5 wt%.

[0019] Compound A of the present invention can be used as a material for external skin preparations (including cosmetics, medicines and quasi-drugs). Examples of forms of the present invention include lotions, soaps, facial cleansers, bath additives, creams, lotions, skin toners, cologne, shaving cream, shaving lotions, cosmetic oils, sunscreen lotions, face powders, foundations, perfumes, masks, nail creams, enamel, enamel removers, eyebrow pencils, blushers, eye creams, eye shadows, mascara, eyeliners, lipsticks, lip balms, shampoos, conditioners, hair dyes, dispersions, cleansers, etc. Examples of the form of pharmaceuticals or quasi-drugs that can be formulated with the present invention include ointments, creams, and liquids for external use. Compound A may be added as is, or may be used as a composition that contains enough compound A to be able to use it as an active ingredient, such as a plant extract, and particularly preferably a rice bran extract. In this case, the content of compound A contained in the rice bran extract is not particularly limited as long as it is an amount that is contained as an active ingredient, but it is preferable to use one that contains, for example, 0.01 to 1 wt%, or even 0.05 to 0.5 wt%.

[0020] In addition to the present invention, topical skin preparations of the above form can contain ingredients that are incorporated into topical skin preparations such as cosmetics and quasi-drugs, as long as they do not impair the function of the present invention, such as oils, higher alcohols, fatty acids, ultraviolet absorbers, powders, pigments, surfactants, polyhydric alcohols / sugars, polymers, physiologically active ingredients, solvents, antioxidants, fragrances, preservatives, etc. Examples are listed below, but the present invention is not limited to these examples.

[0021] (1) Example of oil Ester-based oil phase components: glyceryl tri-2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, isocetyl isostearate, butyl stearate, butyl myristate, ethyl linoleate, isopropyl linoleate, ethyl oleate, isocetyl myristate, isostearyl myristate, isostearyl palmitate, octyldodecyl myristate, isocetyl isostearate, diethyl sebacate, diisopropyl adipate isopropyl, isoarachyl neopentanoate, caprylic / capric triglyceride, trimethylolpropane tri-2-ethylhexanoate, trimethylolpropane triisostearate, pentaerythritol tetra-2-ethylhexanoate, cetyl caprylate, decyl laurate, hexyl laurate, decyl myristate, myristyl myristate, cetyl myristate, stearyl stearate, decyl oleate, cetyl ricinoleate, isostearyl laurate, isotridecyl myristate, isocetyl myristate, isostearate Tearyl, isocetyl palmitate, isostearyl palmitate, octyl stearate, isocetyl stearate, isodecyl oleate, octyldodecyl oleate, octyldodecyl linoleate, isopropyl isostearate, cetostearyl 2-ethylhexanoate, stearyl 2-ethylhexanoate, hexyl isostearate, ethylene glycol dioctanoate, ethylene glycol dioleate, propylene glycol dicaprate, propylene glycol dicaprylate, propylene glycol dicaprylate, dicaprin Neopentyl glycol dioctanoate, neopentyl glycol dioctanoate, glyceryl tricaprylate, glyceryl triundecylate, glyceryl triisopalmitate, glyceryl triisostearate, octyldodecyl neopentanoate, isostearyl octanoate, octyl isononanoate, hexyldecyl neodecanoate, octyldodecyl neodecanoate, isocetyl isostearate, isostearyl isostearate, octyldecyl isostearate, polyglycerin oleate, polyglycerin isostearate, dipropyl carbonate,Dialkyl carbonate (C12-18), triisocetyl citrate, triisoarachidyl citrate, triisooctyl citrate, lauryl lactate, myristyl lactate, cetyl lactate, octyldecyl lactate, triethyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, trioctyl citrate, diisostearyl malate, 2-ethylhexyl hydroxystearate, di-2-ethylhexyl succinate, diisobutyl adipate, diisopropyl sebacate propyl, dioctyl sebacate, cholesteryl stearate, cholesteryl isostearate, cholesteryl hydroxystearate, cholesteryl oleate, dihydrocholesteryl oleate, phytosteryl isostearate, phytosteryl oleate, isocetyl 12-stearoyl hydroxystearate, stearyl 12-stearoyl hydroxystearate, isostearyl 12-stearoyl hydroxystearate, etc. Hydrocarbon-based oil phase components: squalane, liquid paraffin, α-olefin oligomer, isoparaffin, ceresin, paraffin, liquid isoparaffin, polybutene, microcrystalline wax, petrolatum, etc. Animal and vegetable oils and their hydrogenated oils, and waxes of natural origin: beef tallow, hydrogenated beef tallow, lard, hydrogenated lard, horse oil, hydrogenated horse oil, mink oil, orange roughy oil, fish oil, hydrogenated fish oil, egg yolk oil, and other animal oils and their hydrogenated oils, avocado oil, almond oil, olive oil, cocoa butter, kiwi seed oil, apricot kernel oil, kukui nut oil, sesame oil, wheat germ oil, rice germ oil, rice bran oil, safflower oil, shea butter, soybean oil, evening primrose oil, perilla oil, tea seed oil, camellia oil, corn oil, rapeseed oil, These include vegetable oils such as hydrogenated rapeseed oil, palm kernel oil, hydrogenated palm kernel oil, palm oil, hydrogenated palm oil, peanut oil, hydrogenated peanut oil, castor oil, hydrogenated castor oil, sunflower oil, grape seed oil, jojoba oil, hydrogenated jojoba oil, macadamia nut oil, medicamentoil, cottonseed oil, hydrogenated cottonseed oil, coconut oil, hydrogenated coconut oil, and other hydrogenated oils, as well as beeswax, high acid value beeswax, lanolin, reduced lanolin, hydrogenated lanolin, liquid lanolin, carnauba wax, montan wax, and other waxes. Silicone-based oil phase components: dimethylpolysiloxane, methylphenylpolysiloxane, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, methylhydrogenpolysiloxane, polyether-modified organopolysiloxane, dimethylsiloxane-methylcetyloxysiloxane copolymer, dimethylsiloxane-methylstearoxysiloxane copolymer, alkyl-modified organopolysiloxane, terminal-modified organopolysiloxane, amino-modified silicone oil, amino-modified organopolysiloxane, dimethiconol, silicone gel, acrylic silicone, trimethylsiloxysilicate, silicone RTV rubber, etc. Fluorine-based oil phase components: Perfluoropolyether, fluorine-modified organopolysiloxane, fluorinated pitch, fluorocarbon, fluoroalcohol, fluoroalkyl-polyoxyalkylene co-modified organopolysiloxane, etc.

[0022] (2) Examples of higher alcohols Examples include lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, behenyl alcohol, 2-ethylhexanol, hexadecyl alcohol, and octyldodecanol.

[0023] (3) Examples of fatty acids Examples of these acids include caprylic acid, capric acid, undecylenic acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, isostearic acid, oleic acid, linoleic acid, linolenic acid, arachidic acid, arachidonic acid, behenic acid, erucic acid, and 2-ethylhexanoic acid.

[0024] (4) Examples of UV absorbers p-aminobenzoic acid, amyl p-aminobenzoate, dihydroxypropyl ethyl p-aminobenzoate, glyceryl p-aminobenzoate, ethyl p-aminobenzoate, octyl p-aminobenzoate, dimethyl octyl p-aminobenzoate, ethylene glycol salicylate, octyl salicylate, triethanolamine salicylate, phenyl salicylate, butylphenyl salicylate, benzyl salicylate, homomenthyl salicylate, benzyl cinnamate, octyl p-methoxycinnamate, 2-ethylhexyl p-methoxycinnamate, glyceryl di-p-methoxycinnamate mono 2-ethylhexanoate, isopropyl p-methoxycinnamate, diethanolamine salt of p-methoxyhydrocinnamic acid, mixture of diisopropyl and diisopropyl cinnamate, urocanic acid, ethyl urocanate, hydroxymethoxybenzophenone, hydroxymethoxybenzophenone sulfonic acid and its salts, di Hydroxymethoxybenzophenone, dihydroxymethoxybenzophenone sodium disulfonate, dihydroxybenzophenone, dihydroxydimethoxybenzophenone, hydroxyoctoxybenzophenone, tetrahydroxybenzophenone, butyl methoxydibenzoylmethane, 2,4,6-trianilino-p-(carbo-2-ethylhexyl-1-oxy)-1,3,5-triazine, 2-(2-hydroxy-5-methylphenyl)benzotriazole, methyl-O-aminobenzoate, 2-ethylhexyl-2-cyano-3,3-diphenylacrylate, phenylbenzimidazole sulfate, 3-(4-methylbenzylidene)camphor, isopropyl dibenzoylmethane, 4-(3,4-dimethoxyphenylmethylene)-2,5-dioxo-1-imidazolidinepropionic acid 2-ethylhexyl, and the like, as well as their polymer derivatives and silane derivatives.

[0025] (5) Examples of powders and pigments Dyes such as Red No. 104, Red No. 201, Yellow No. 4, Blue No. 1, Black No. 401, lake dyes such as Yellow No. 4 AL Lake, Yellow No. 203 BA Lake, nylon powder, silk powder, urethane powder, Teflon (registered trademark) powder, silicone powder, polymethyl methacrylate powder, cellulose powder, starch, silicone elastomer spherical powder, polyethylene powder and other polymers, yellow iron oxide, red iron oxide, black iron oxide, chromium oxide, carbon black, ultramarine, Prussian blue and other colored pigments, zinc oxide, titanium oxide, acid Examples of such pigments include white pigments such as cerium chloride, extender pigments such as talc, mica, sericite, kaolin, and plate-like barium sulfate, pearl pigments such as titanium mica, metal salts such as barium sulfate, calcium carbonate, magnesium carbonate, aluminum silicate, and magnesium silicate, inorganic powders such as silica and alumina, metal soaps such as aluminum stearate, magnesium stearate, zinc palmitate, zinc myristate, magnesium myristate, zinc laurate, and zinc undecylenate, bentonite, smectite, and boron nitride. There are no particular limitations on the shape (spherical, rod-like, needle-like, plate-like, irregular, flaky, spindle-like, etc.) and particle size of these powders. These powders may or may not have been previously surface-treated using conventional surface treatments, such as fluorine compound treatment, silicone treatment, silicone resin treatment, pendant treatment, silane coupling agent treatment, titanium coupling agent treatment, oil treatment, N-acylated lysine treatment, polyacrylic acid treatment, metal soap treatment, amino acid treatment, lecithin treatment, inorganic compound treatment, plasma treatment, mechanochemical treatment, etc.

[0026] (6) Examples of surfactants Anionic surfactants: fatty acid soap, α-acylsulfonate, alkylsulfonate, alkylarylsulfonate, alkylnaphthalenesulfonate, alkyl sulfate, POE alkyl ether sulfate, alkylamide sulfate, alkyl phosphate, POE alkyl phosphate, alkylamide phosphate, alkyloylalkyl taurine salt, N-acylamino acid salt, POE alkyl ether carboxylate, alkylsulfosuccinate, sodium alkylsulfoacetate, acylated hydrolyzed collagen peptide salt, perfluoroalkyl phosphate ester, etc. Cationic surfactants: alkyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, cetostearyltrimethylammonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, behenyltrimethylammonium bromide, benzalkonium chloride, behenic acid amidopropyldimethylhydroxypropylammonium chloride, stearic acid diethylaminoethylamide, stearic acid dimethylaminopropylamide, lanolin derivative quaternary ammonium salts, etc. Amphoteric surfactants: Examples of amphoteric surfactants include carboxybetaine type, amidobetaine type, sulfobetaine type, hydroxysulfobetaine type, amidosulfobetaine type, phosphobetaine type, aminocarboxylate type, imidazoline derivative type, and amidoamine type. Nonionic surfactants: Propylene glycol fatty acid esters, glycerin fatty acid esters, polyglycerin fatty acid esters, sorbitan fatty acid esters, POE sorbitan fatty acid esters, POE sorbitol fatty acid esters, POE glycerin fatty acid esters, POE alkyl ethers, POE fatty acid esters, POE hydrogenated castor oil, POE castor oil, POE·POP copolymers, POE·POP alkyl ethers, polyether modified silicone lauric acid alkanolamide, alkylamine oxide, hydrogenated soybean phospholipids, etc. Natural surfactants: These include lecithin, saponin, sugar-based surfactants, etc.

[0027] (7) Examples of polyhydric alcohols and sugars Examples of suitable sugars include ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, glycerin, diglycerin, polyglycerin, 3-methyl-1,3-butanediol, 1,3-butylene glycol, sorbitol, mannitol, raffinose, erythritol, glucose, sucrose, fructose, xylitol, lactose, maltose, maltitol, trehalose, alkylated trehalose, mixed isomerized sugar, sulfated trehalose, pullulan, etc. Chemically modified versions of these sugars can also be used.

[0028] (8) Examples of polymers Acrylic acid ester / methacrylic acid ester copolymer (Pluscise, GOO Chemical Co., Ltd.), vinyl acetate / crotonic acid copolymer (Resin 28-1310, NSC Co., Ltd.), vinyl acetate / crotonic acid / vinyl neodecanoate copolymer (28-2930, NSC Co., Ltd.), methyl vinyl ether maleic acid half ester (Gantrez ES, ISP Co., Ltd.), t-butyl acrylate / ethyl acrylate / methacrylic acid copolymer (Ruvimer, BASF Co., Ltd.), vinyl pyrrolidone / vinyl acetate / vinyl propionate copolymer (Ruviscol VAP, BASF Co., Ltd.), vinyl acetate Vinyl acetate / crotonic acid copolymer (Rubyset CA, BASF), vinyl acetate / crotonic acid / vinyl pyrrolidone copolymer (Rubyset CAP, BASF), vinyl pyrrolidone / acrylate copolymer (Rubyflex, BASF), acrylate / acrylamide copolymer (Ultrahold, BASF), vinyl acetate / butyl maleate / isobornyl acrylate copolymer (Advantage, ISP), carboxyvinyl polymer (Carbopol, BFGoodrich), acrylic acid / alkyl methacrylate copolymer (Pemulen, BF Examples of such polymer compounds include anionic polymer compounds such as dialkylaminoethyl methacrylate polymer acetic acid amphoteric acid (Yukaformer, manufactured by Mitsubishi Chemical Corporation) and octylacrylamide acrylate / hydroxypropyl acrylate / butylaminoethyl methacrylate copolymer (AMPHOMER, manufactured by NSC Corporation); cationic polymer compounds such as vinylpyrrolidone / dimethylaminoethyl methacrylate quaternary acid (GAFQUAT, manufactured by ISP Corporation) and methylvinylimidazolium chloride / vinylpyrrolidone copolymer (Rubycoat, manufactured by BASF Corporation); and nonionic polymer compounds such as polyvinylpyrrolidone (Ruviscol K, manufactured by BASF Corporation), vinylpyrrolidone / vinyl acetate copolymer (Ruviscol VA, manufactured by BASF Corporation), vinylpyrrolidone / dimethylaminoethyl methacrylate copolymer (Copolymer 937, manufactured by ISP Corporation), and vinylcaprolactam / vinylpyrrolidone / dimethylaminoethyl methacrylate copolymer (Copolymer VC713, manufactured by ISP Corporation).In addition, naturally occurring polymeric compounds such as cellulose or its derivatives, keratin and collagen or its derivatives, calcium alginate, pullulan, agar, gelatin, tamarind seed polysaccharides, xanthan gum, carrageenan, high methoxyl pectin, low methoxyl pectin, guar gum, gum arabic, crystalline cellulose, arabinogalactan, karaya gum, tragacanth gum, alginic acid, albumin, casein, curdlan, gellan gum, and dextran can also be suitably used.

[0029] (9) Examples of physiologically active ingredients Examples of physiologically active ingredients include substances that impart some kind of physiological activity to the skin when applied to the skin. For example, whitening ingredients, immune activators, anti-aging agents, UV protection agents, slimming agents, tightening agents, antioxidants, hair growth agents, hair restorers, moisturizers, blood circulation promoters, antibacterial agents, bactericides, drying agents, cooling agents, warming agents, vitamins, amino acids, wound healing promoters, irritation relievers, painkillers, cell activators, enzyme ingredients, etc. Examples of suitable ingredients include angelica extract, avocado extract, amacha extract, altea extract, arnica extract, aloe extract, apricot extract, apricot kernel extract, ginkgo extract, fennel extract, turmeric extract, oolong tea extract, eijitsu extract, echinacea leaf extract, scutellaria extract, phellodendron bark extract, coptis extract, barley extract, hypericum extract, white nettle extract, watercress extract, orange extract, Dried seawater, seaweed extract, hydrolyzed elastin, hydrolyzed wheat powder, hydrolyzed silk, chamomile extract, carrot extract, artemisia capillaris extract, licorice extract, kalk extract, kakyoku extract, cinchona extract, cucumber extract, guanosine, gardenia extract, kumazasa extract, sophora flavescens extract, walnut extract, grapefruit extract, clematis extract, chlorella extract, mulberry extract, gentiana extract, black tea extract, yeast extract, burdock extract, cocos Fermented rice bran extract, rice germ oil, comfrey extract, collagen, bilberry extract, Chinese ivy extract, Chinese rhizome extract, umbilical cord extract, salvia extract, soapwort extract, bamboo extract, hawthorn extract, Japanese pepper extract, shiitake mushroom extract, rehmannia extract, lithospermum extract, perilla extract, linden extract, meadowsweet extract, peony extract, calamus root extract, white birch extract, horsetail extract, ivy extract, hawthorn extract, se Elderberry extract, yarrow extract, peppermint extract, sage extract, mallow extract, cnidium extract, swertia britannica extract, soybean extract, chinese laurel extract, thyme extract, tea extract, clove extract, imperata cylindrica extract, tangerine extract, angelica extract, calendula extract, peach kernel extract, spruce extract, houttuynia extract, tomato extract, natto extract, carrot extract, garlic extract, wild rose extract, hibiscus extract,Bakumondou extract, parsley extract, honey, witch hazel extract, parietaria extract, yarrow extract, bisabolol, loquat extract, coltsfoot extract, butterbur bud extract, bupleurum extract, butcher's broom extract, grape extract, propolis, loofah extract, safflower extract, peppermint extract, linden extract, peony extract, hop extract, pine extract, horse chestnut extract, skunk cabbage extract, soapberry extract, melissa extract, peach extract, cornflower extract, eu Examples of such extracts include potassium extract, saxifrage extract, coix seed extract, mugwort extract, lavender extract, apple extract, lettuce extract, lemon extract, astragalus extract, rose extract, rosemary extract, Roman chamomile extract, royal jelly extract, placenta, yuzu seed extract, blueberry extract, lingonberry extract, Cistanche Tubulosa extract, black rice extract, green coffee bean extract, resveratrol, kiwi seed extract, strawberry seed extract, cherry blossom extract, and kudzu lactic acid bacteria. In addition, it contains biopolymers such as deoxyribonucleic acid, mucopolysaccharides, sodium hyaluronate, sodium chondroitin sulfate, collagen, elastin, chitin, chitosan, and hydrolyzed eggshell membrane, moisturizing ingredients such as amino acids, hydrolyzed peptides, sodium lactate, urea, sodium pyrrolidone carboxylate, betaine, whey, and trimethylglycine, oily ingredients such as sphingolipids, ceramides, phytosphingosine, cholesterol, cholesterol derivatives, and phospholipids, ε-aminocaproic acid, glycyrrhizic acid, β-glycyrrhetinic acid, lysozyme chloride, and guaiazure. immune stimulants such as sucrose and hydrocortisone; vitamins such as vitamin A, vitamin B2, vitamin B6, vitamin C, vitamin D, vitamin E, calcium pantothenate, biotin, nicotinamide, vitamin C ester; active ingredients such as allantoin, diisopropylamine dichloroacetate, and 4-aminomethylcyclohexane carboxylic acid; antioxidants such as tocopherol, carotenoids, flavonoids, tannins, lignans, and saponins; cell stimulants such as alpha-hydroxy acids and beta-hydroxy acids; blood circulation promoters such as gamma-oryzanol and vitamin E derivatives. Wound healing agents such as retinol and retinol derivatives, skin whitening agents such as arbutin, kojic acid, placenta extract, sulfur, ellagic acid, linoleic acid, tranexamic acid, and glutathione, cepharanthine, licorice extract, capsicum tincture, hinokitiol, iodized garlic extract, pyridoxine hydrochloride, DL-α-tocopherol, DL-α-tocopherol acetate, nicotinic acid, nicotinic acid derivatives, calcium pantothenate, D-pantothenyl alcohol, acetyl pantothenyl ethyl ether, biotin, allantoin, isopropyl methylphenol, estradiol, All, ethinyl estradiol, capronium chloride, benzalkonium chloride, diphenhydramine hydrochloride, tacanal, camphor, salicylic acid, vanillylamide nonylate, vanillylamide nonanoate, piroctone olamine, glyceryl pentadecanoate, L-menthol, mononitroguaiacol, resorcinol, gamma-aminobutyric acid, benzethonium chloride, mexiletine hydrochloride, auxin, female hormones, cantharides tincture, cyclosporine, zinc pyrithione, hydrocortisone, minoxidil, polyoxyethylene sorbitan monostearate, peppermint oil,These include hair growth agents such as Sasanishiki extract, placenta, yuzu seed extract, blueberry extract, lingonberry extract, Cistanche Tubulosa extract, black rice extract, green coffee bean extract, resveratrol, kiwi seed extract, strawberry seed extract, cherry blossom extract, and kudzu lactic acid bacteria.

[0030] (10) Examples of antioxidants Examples of antioxidants include sodium bisulfite, sodium sulfite, erythorbic acid, sodium erythorbate, dilauryl thiodipropionate, tocopherol, tolylbiguanide, nordihydroguaiaretic acid, parahydroxyanisole, butylated hydroxyanisole, dibutylhydroxytoluene, ascorbyl stearate, ascorbyl palmitate, octyl gallate, propyl gallate, carotenoids, flavonoids, tannins, lignans, saponin, and plant extracts such as apple extract and clove extract that are known to have antioxidant effects.

[0031] (11) Examples of solvents Examples include purified water, ethanol, lower alcohols, ethers, LPG, fluorocarbons, N-methylpyrrolidone, fluoroalcohols, volatile linear silicones, and next-generation fluorocarbons. EXAMPLES

[0032] Examples of the present invention will be described below. Note that the examples shown below are described to confirm the various actions and effects of the agent of the present invention obtained by the present invention, and the scope of the present invention is not limited to these products and manufacturing methods.

[0033] Example: Preparation of Compound A 1. Preparation of Compound A A fraction (15.4 g) enriched in glucosylceramide (GlcCer) from a by-product obtained during the rice bran oil manufacturing process was subjected to medium-pressure silica gel chromatography (column: Universal Column Premium, 3 L, Yamazen Corporation), washed with ethyl acetate for 20 min, and then eluted with a gradient of chloroform:methanol (95:5→50:50, v / v, 50 min). The fraction (580 mg) obtained by concentrating and drying the eluate from the 95:5→90:10 gradient was crudely purified by HPLC [column: CAPCELLPAK C18, 250 mm × inner diameter 20 mm (Shiseido), eluent: methanol:THF=90:10, detection: RI, flow rate 9 mL / min], and then further purified by HPLC [column: Sunrise C30, 250 mm × inner diameter 20 mm (Chromanik Technologies), eluent: methanol:THF=90:10, detection: RI, flow rate 9 mL / min] to obtain a new component (8.0 mg) as a white powder.

[0034] 2. Identification of the structure of compound A The optical rotation, mass spectrometry and infrared absorption spectrum of the obtained components were 1 H and 13 C-NMR spectrum was measured. 1) Physicochemical data White powder. [α] D 25 199.1° (c=0.15, MeOH). High resolution ESI-MS Calcd for C 60 H 113 NO 10 Na (M+Na) + : ; Found: 1030.8243, IR (KBr, cm -1 ): 3410, 2918, 2843, 1732, 1653, 1527, 1467, 1078. 1H-NMR (C5D5N, 800 MHz) δ: 0.88 (3H×2, t, J=7.3 Hz 18, 20'-H), 0.89 (3H, t, J=7.3 Hz 16'''-H), 1.27 (2H×3, m, 16, 18', 14'''-H), 1.28 (2H×3, m, 17, 19', 15'''-H), 1.28-1.31 (m, 11-15, 5'-17', 4'''-13'''-H) 1.65 (2H, tt, J=7.6, 7.8 Hz, 3'''-H), 1.72 (1H, m, 4'a-H), 1.80 (1H, m, 4'b-H), 2.00 (1H, m, 3'a-H), 2.10 (2H, m, 10-H), 2.20 (2H, m, 6-H), 2.20 (1H, m, 3'b-H), 2.22 (2H, m, 7-H), 2.36 (2H, m, 2'''-H), 3.98 (1H, ddd, J=2.1, 5.7, 9.2 Hz, 5''-H), 4.00 (1H, dd, J=7.8, 8.9 Hz, 2''-H), 4.04 (1H, dd, J=8.9, 9.2 Hz, 4''-H), 4.16 (1H, dd, J=8.7, 8.7 Hz, 3''-H), 4.26 (1H, dd, J=3.9, 10.7 Hz, 1a-H), 4.55 (1H, m, 2'-H), 4.71 (1H, dd, J=6.2, 10.7 Hz, 1b-H),4.73 (1H, m, 3-H), 4.75 (1H, dd, J=5.7, 11.7 Hz, 6''a-H), 4.78 (1H, m, 2-H), 4.88 (1H, d, J=7.8 Hz, 1''-H), 4.96 (1H, dd, J=2.1, 11.7 Hz, 6''b-H), 5.50 (2H, m, 8,9-H), 5.95 (1H, dd, J=15.6, 6.4 Hz, 5-H), 6.00 (1H, dd, J=6.2, 15.6 Hz, 4-H), 8.29 (1H, d, J=8.9 Hz, NH). 13 C-NMR (C5D5N, 200 MHz) δ C: 70.2 (C-1), 54.6 (C-2), 72.5 (C-3), 132.2 (C-4), 132.1 (C-5), 32.9 (C-6), 27.4 (C-7), 129.5 (C-8), 130.7 (C-9), 27.6 (C-10), 29.5, 29.6, 29.8, 29.9, 30.0, 30.1 (C-11-15), 32.1 (C-16), 22.9 (C-17), 14.3 (C-18), 175.7 (C-1'), 72.5 (C-2'), 34.4 (C-3'), 25.9 (C-4'), 29.5, 29.6, 29.8, 29.9, 30.0, 30.1 (C-5'-17'), 32.1 (C-18'), 22.9 (C-19'), 14.3 (C-20'), 105.5 (C-1''), 75.4 (C-2''), 78.3 (C-3''), 71.5 (C-4''), 75.0 (C-5''), 64.6 (C-6''), 173.7 (C-1'''), 34.4 (C-2'''), 25.3 (C-3'''), 29.5, 29.6, 29.8, 29.9, 30.0, 30.1 (C-4'''-13'''), 32.1 (C-14'''), 22.9 (C-15'''), 14.3 (C-16'''). Positive-ion ESI-MS: m / z 1030 (M+Na) + .

[0035] 2) Two-dimensional NMR HMQC ( 1 H-detected multiple quantum coherence spectrum), HMBC ( 1 H-detected multi-bond heteronuclear multiple quantum coherence spectrum) and 1 H- 1 As a result of H COSY (correlation spectroscopy) analysis, the proton-carbon correlation shown by the arrows in Figure 1 and the proton-proton correlation shown by the thick line were observed.

[0036] 3) Identification of acyl groups and GlcCer molecular species Identification of the acyl groups by solvolysis was carried out as follows. The new compound (1.0 mg) was dissolved in 0.5% sodium methoxide / methanol solution (500 μL) and reacted on ice for 3 hours, after which 1% acetic acid / methanol solution (500 μL) was added to the reaction solution. To identify the acyl groups, the reaction solution was subjected to reversed-phase HPLC [column: CAPCELLPAK C18 SG-120, 250 mm × inner diameter 4.6 mm (Shiseido), eluent: acetonitrile:methanol:water = 75:11:14, detection: CAD, flow rate 1 mL / min; column temperature: 40 °C], and the retention time of the fatty acid methyl ester of the derivative was compared with the retention time of the standard (t R The acyl group was identified as palmitic acid by comparing the retention times (t : methyl palmitate; 25.4 min, methyl oleate; 26.3 min, methyl linoleate; 13.8 min) of the standard samples. The GlcCer molecular species was identified by subjecting the reaction mixture to a column (CAPCELLPAK C18 SG-120, 250 mm × 4.6 mm inner diameter (Shiseido), eluent: methanol, detection: CAD, flow rate: 1 mL / min; column temperature: 40 °C) and comparing the retention time of the derivative GlcCer with that of the standard sample (t R : GlcCer[d18:2(4E,8Z / 20:0)]; 7.1 min,GlcCer[d18:2(4E,8E / 20:0)]; 7.3 min) and identified the GlcCer molecular species as GlcCer[d18:2(4E,8Z / 20:0)]. From the above physicochemical data, it was determined that this novel component is 6"-O-palmitoyl-GlcCer[d18:2(4E,8Z / 20:0)] (compound A), in which palmitic acid is ester-linked to the 6" position of the glucose unit of GlcCer[d18:2(4E,8Z / 20:0)].

[0037] Test Example 1: Effect of Compound A on transepidermal water loss in a 3D human epidermis model 1. Test Method For the human epidermis 3D model, J-Tec's LabCyte EPI-MODEL (24-well) was used. 6"-O-palmitoyl-GlcCer[d18:2(4E,8Z / 20:0)] was added to the culture medium to final concentrations of 1, 3, and 10 μM, and transmembrane TEWL was measured on days 0, 1, 3, 5, and 7 of culture. TEWL was measured using Integral's Tewitro24, and evaluated as the amount of change from day 0 of addition. The results are shown in Figure 2.

[0038] 2. Measurement Results and Effects of the Example in Test Example 1 As shown in Figure 2, the change in TEWL of a human epidermis 3D model cultured with the addition of compound A is shown. As a result of the experiment, compound A reduced TEWL in a concentration-dependent manner, and a significant reduction was confirmed at 10 μM. As a result of evaluating the effect of compound A on the TEWL of a human epidermis 3D model, a concentration-dependent TEWL improvement effect was confirmed.

[0039] Test Example 2: Immunostimulatory effect of Compound A 1. Test Method (1) Cultivation method of mouse macrophage-derived cells (Raw264.7) Raw264.7 cells derived from mouse macrophages were cultured and used for the experiment. The medium used was Dulbecco's Modified Eagles Medium (D-MEM containing 1000 mg / L glucose) supplemented with 10 (v / v) % FBS (and 100 units / mL penicillin G and 100 μg / mL streptomycin). The cells were cultured in a 75 cm 2 The culture was carried out in a culture flask at 37°C in the presence of 5% CO2. The cultured cells were washed twice with PBS(-) and then detached from the flask with a phenol red-containing 0.25 w / v% Trypsin-1 mM EDTA·4Na solution for use in the experiment.

[0040] (2) Evaluation of the effect of cytokines (IL-6) on gene expression in mouse macrophage-derived Raw264.7 cells Raw264.7 cells were seeded in a 12-well plate (1.0 × 10 5 The cells were cultured for 48 hours (100 x 100 cells / well). After that, the medium was replaced with medium containing the test substance, and the cells were cultured for 24 hours. After the culture, RNA was extracted from the cells, and gene expression levels were measured according to the RT-PCR method. The results are shown in Figure 3.

[0041] 2. Results and Effects of the Examples in Test Example 2 As shown in Figure 3, the addition of compound A to macrophages (Raw264.7) significantly increased the amount of IL-6 gene expression in the cells. Therefore, it was revealed that compound A has an immunostimulatory effect in macrophages.

[0042] The following are formulation examples of the rice bran extract (compound A 0.05 to 0.5%) containing compound A of the present invention. Note that the following formulation examples do not limit the present invention. Formulation example 1: Chewing gum Sugar 53.0wt% Gum base 20.0 Glucose 10.0 Starch syrup 16.0 Fragrance 0.5 Rice bran extract 0.5 100.0wt%

[0043] Mixture Example 2: Gummies Reduced starch syrup 40.0wt% Granulated sugar 20.0 Glucose 20.0 Gelatin 4.7 Wednesday 9.68 Yuzu juice 4.0 Yuzu flavor 0.6 Dye 0.02 Rice bran extract 1.0 100.0wt%

[0044] Mixture example 3: Candy Sugar 50.0wt% Syrup 33.0 Wednesday 14.4 organic acid 2.0 Fragrance 0.2 Rice bran extract 0.4 100.0wt%

[0045] Mixture example 4: Yogurt (hard / soft) Milk 41.5wt% Skim milk powder 5.8 Sugar 8.0 Agar 0.15 Gelatin 0.1 Lactic acid bacteria 0.005 Rice bran extract 0.4 fragrance trace amount water residue 100.0wt%

[0046] Formulation example 5: Soft drink Fructose glucose liquid sugar 30.0wt% Emulsifier 0.5 Rice bran extract 0.3 Fragrance (appropriate amount) Purified water remainder 100.0wt%

[0047] Formulation example 6: Tablet confectionery Sugar 76.4wt% Glucose 19.0 Sucrose fatty acid ester 0.2 Rice bran extract 0.5 Purified water 3.9 100.0wt%

[0048] Formulation example 7: Soft capsule Brown rice germ oil 47.0wt% Yuzu seed oil 40.0 Emulsifier 12.0 Rice bran extract 1.0 100.0wt%

[0049] Formulation Example 8: Tablets Lactose 54.0wt% Crystalline cellulose 30.0 Starch decomposition product 10.0 Glycerin fatty acid ester 5.0 Rice bran extract 1.0 100.0wt%

[0050] Formulation example 9: Cosmetic cream Squalane 20.0wt% Beeswax 5.0 Refined Jojoba Oil 5.0 Glycerin 5.0 Glycerin Monostearate 2.0 Polyoxyethylene (20) Sorbitan- Monostearate 2.0 Strawberry Seed Extract 0.1 Glucosylceramide 0.1 Rice bran extract 1.0 Preservatives (appropriate amount) Fragrance (appropriate amount) Purified water remainder 100.0wt%

[0051] Formulation example 10: Lotion Ethanol 5.0wt% Glycerin 2.0 1,3-Butylene glycol 2.0 Polyethylene oleyl ether 0.5 Sodium citrate 0.1 Citric acid 0.1 Strawberry Seed Extract 0.1 Glucosylceramide 0.1 Rice bran extract 0.1 Purified water remainder 100.0wt%

[0052] Formulation example 11: Body gel Macadamia nut oil 2.0wt% Octyldodecyl myristate 10.0 Methylphenylpolysiloxane 5.0 Behenyl Alcohol 3.0 Stearic Acid 3.0 Batyl alcohol 1.0 Glyceryl Monostearate 1.0 Polyoxyethylene sorbitol tetraoleate 2.0 Hydrogenated soy phospholipids 1.0 Ceramide 0.1 Retinol Palmitate 0.1 Preservatives (appropriate amount) Centella asiatica extract 1.0 Strawberry Seed Extract 0.1 Glucosylceramide 0.1 Rice bran extract 1.0 1,3-Butylene glycol 5.0 Purified water remainder 100.0wt%

[0053] Formulation example 12: Emulsion Squalane 4.0wt% Vaseline 2.5 Cetanol 2.0 Glycerin 2.0 Lipophilic glyceryl monostearate 1.0 Stearic acid 1.0 L-Arginine 1.0 Strawberry Seed Extract 0.1 Glucosylceramide 0.1 Rice bran extract 0.5 Potassium hydroxide 0.1 fragrance trace amount Purified water remainder 100.0wt%

[0054] Formulation example 13: Bath additive (liquid) Propylene glycol 50.0wt% Ethanol 20.0 Sodium sulfate 5.0 Strawberry Seed Extract 0.1 Glucosylceramide 0.1 Rice bran extract 0.5 Lanolin 0.5 Avocado oil 0.5 Dye 1.5 Fragrance 22.0 100.0wt% Formulation example 14: Shampoo Sodium polyoxyethylene alkyl ether sulfate (E.O2 moles) 15.0 Coconut oil fatty diethanolamide 5.0 Glycerin 3.0 Strawberry Seed Extract 0.1 Glucosylceramide 0.1 Rice bran extract 0.4 Ethanol 5.0 Fragrances and preservatives Appropriate amount Ion exchange water Residual Total 100wt%

[0055] Formulation example 15: Hair cream Liquid paraffin 20.0wt% Solid Paraffin 3.0 Polyoxyethylene cetyl ether (E.O 15 moles) 2.0 Sorbitan Sesquioleate 1.0 Strawberry Seed Extract 0.1 Glucosylceramide 0.1 Rice bran extract 0.2 Ethanol 10.0 Potassium hydroxide 0.1 Glycerin 3.0 Fragrances and preservatives Appropriate amount Total 100wt%

[0056] Formulation example 16: Ointment White beeswax 5.0wt% Refined Lanolin 5.0 Strawberry Seed Extract 0.1 Glucosylceramide 0.1 Rice bran extract 1.0 Fragrance 0.1 Vaseline Residue Total 100wt% [Industrial Applicability]

[0057] As described above, the present invention can provide a novel compound and its use.

Claims

1. A compound represented by the following chemical formula (1): 【Chemistry 1】

2. 13. An immunostimulant comprising the compound of claim 1 as an active ingredient.

3. A moisturizing agent comprising the compound according to claim 1 as an active ingredient.

4. A method for producing the compound of claim 1, comprising the step of isolating the compound of claim 1 from an extract of rice bran.

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