Body odor-causing substance secretion inhibitor

Abstract

To provide a novel agent for inhibiting secretion of a body odor-causing substance.SOLUTION: An agent for inhibiting the secretion of a body odor-causing substance contains flavonoid as an active ingredient. The flavonoid is at least one selected from the group consisting of isoflavonoid, flavanonol, flavone, flavanone, flavonol, chalcone, catechin and glycosides thereof, and salts thereof.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to an inhibitor for suppressing the secretion of body odor-causing substances.

Background Art

[0002] ABCC11, which is a type of ATP-Binding Cassette (ABC) transporter, is a protein that is expressed in apocrine glands and transports various substrates. ABCC11 is known to have a wild type in which the 180th amino acid is Gly and a mutant type in which this is mutated to Arg. Also, wild-type ABCC11 / mutant-type ABCC11 determines the earwax type in humans, resulting in a wet-type / dry-type expression system, respectively.

[0003] In recent years, the relationship between wild-type ABCC11 / mutant-type ABCC11 and body odor (for example, axillary osmidrosis) has attracted attention. For example, Non-Patent Document 1 describes that in the secretory cells of apocrine glands, ABCC11 takes up body odor-causing substances into vesicles, and the vesicles that have taken up the body odor-causing substances separate from the secretory cells, move from the dermis to the epidermis, and release the body odor-causing substances on the skin surface, and these are converted into body odor components by skin commensal bacteria.

Prior Art Documents

Non-Patent Documents

[0004]

Non-Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] Currently, as body odor care products, products that apply methods such as killing skin commensal bacteria and suppressing the secretion of sweat (moisture) to suppress the activities of skin commensal bacteria are mainstream. Almost none are known to suppress the secretion of the body odor-causing substances themselves.

[0006] The inventors have found that flavonoids have the effect of inhibiting the transport activity of ABCC11. By inhibiting the transport activity of ABCC11, it is possible to suppress the uptake of body odor-causing substances into vesicles in the secretory cells of apocrine glands, and thus it is considered that the secretion of body odor-causing substances can be suppressed at the source. The present invention is based on this new finding and aims to provide a novel body odor-causing substance secretion inhibitor.

Means for Solving the Problems

[0007] The present invention relates to a body odor-causing substance secretion inhibitor containing flavonoids as an active ingredient.

[0008] The body odor-causing substance secretion inhibitor according to the present invention contains flavonoids as an active ingredient. Therefore, due to the action of flavonoids inhibiting the transport activity of ABCC11, it is possible to suppress the uptake of body odor-causing substances into vesicles in the secretory cells of apocrine glands, and it is possible to suppress the secretion of body odor-causing substances from apocrine glands to the epidermis.

[0009] The above flavonoids may be at least one selected from the group consisting of isoflavonoids, flavananols, flavones, flavanones, flavonols, chalcones, catechins and their glycosides, and salts thereof. Thereby, the above-described effects can be exhibited more remarkably.

[0010] The present invention also relates to a food composition for suppressing the secretion of body odor-causing substances, containing flavonoids as an active ingredient.

[0011] The present invention further relates to a pharmaceutical composition, quasi-drug composition or cosmetic composition for suppressing the secretion of body odor-causing substances, containing flavonoids as an active ingredient.

Effects of the Invention

[0012] According to the present invention, a novel body odor-causing substance secretion inhibitor can be provided.

Modes for Carrying Out the Invention

[0013] Hereinafter, embodiments for carrying out the present invention will be described in detail. However, the present invention is not limited to the following embodiments.

[0014] The body odor-causing substance secretion inhibitor according to this embodiment contains flavonoids as an active ingredient.

[0015] The body odor-causing substance secretion inhibitor according to this embodiment has an action of inhibiting the transport activity of ABCC11 (transporter), and thus can suppress the uptake of body odor-causing substances into vesicles in the secretory cells of apocrine glands, and can suppress the secretion of body odor-causing substances from apocrine glands to the epidermis. In this specification, the "body odor-causing substance" includes a substance that has an odor by itself and is one of the causes of body odor, and a substance that is converted into a substance having an odor by the action of skin commensal bacteria and is one of the causes of body odor.

[0016] The flavonoids as the active ingredient are a group of plant-derived aromatic compounds having a basic skeleton composed of 15 carbon atoms of C6-C3-C6. In this embodiment, the flavonoids may be derived from natural products (plants, microorganisms, etc.) or may be artificially synthesized. Also, if there are commercially available ones, they may be used. The flavonoids may be obtained, for example, by extracting from plant seeds, leaves, branches, roots, flowers, etc. with water, hot water, ethanol, methanol, etc.

[0017] Examples of flavonoids include isoflavonoids, flavanols, flavones, flavanones, flavonols, chalcones, catechins and their glycosides, and salts thereof.

[0018] In this specification, isoflavonoids refer to isoflavones and isoflavans, and their metabolites.

[0019] In this specification, isoflavone refers to a compound having an isoflavone skeleton. The isoflavone may be, for example, a compound represented by the following formula (1). In the general formula (1), R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 and R 19 each independently represent a hydrogen atom, a hydroxyl group (-OH) or a methoxy group (-OCH 3 ). Examples of isoflavones include genistein (R 12 , R 15 and R 17 : hydroxyl group, R 10 , R 11 , R 13 , R 14 , R 16 , R 18 and R 19 : hydrogen atom), daidzein (R 12 and R 17 : hydroxyl group, R 10 , R 11 , R 13 , R 14 , R 15 , R 16 , R 18 and R 19 : hydrogen atom), and the like.

[0020]

Chemical formula

[0021] In this specification, isoflavan refers to a compound having an isoflavan skeleton. The isoflavan may be, for example, a compound represented by the following formula (2). In the general formula (2), R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 and R29 each independently represents a hydrogen atom, a hydroxyl group (-OH) or a methoxy group (-OCH 3 ). Examples of isoflavans include equol (R 22 and R 27 : hydroxyl group, R 20 , R 21 , R 23 , R 24 , R 25 , R 26 , R 28 and R 29 : hydrogen atom), etc.

[0022]

Chemical formula

[0023] Examples of metabolites of isoflavones and isoflavans include dihydrodaidzein, dihydrogenistein, O-desmethylangolensin, 6-hydroxy-O-desmethylangolensin, genistein 7-β-D-glucuronide 4'-sulfate. In this specification, among the metabolites of isoflavones and isoflavans, compounds that meet the above definitions of isoflavones or isoflavans are regarded as isoflavones or isoflavans.

[0024] Examples of glycosides of isoflavonoids include puerarin, daidzin, etc. The salts of isoflavonoids may be salts acceptable as foods, pharmaceuticals, quasi-drugs or cosmetics, and examples include alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as magnesium salt and calcium salt, ammonium salt, etc.

[0025] In this specification, flavanol refers to a compound having a flavanol skeleton. Flavanol may be, for example, a compound represented by the following formula (3). In the general formula (3), R 30 , R 31 , R 32 , R 33 , R 34 , R 35, R 36 , R 37 and R 38 each independently represents a hydrogen atom, a hydroxyl group (-OH) or a methoxy group (-OCH 3 ). Examples of flavononols include, for example, taxifolin (R 32 , R 33 , R 35 and R 37 : hydroxyl group, R 30 , R 31 , R 34 , R 36 and R 38 : hydrogen atom), dihydromyricetin (R 31 , R 32 , R 33 , R 35 and R 37 : hydroxyl group, R 30 , R 34 , R 36 and R 38 : hydrogen atom), etc.

[0026]

Chemical formula

[0027] Examples of glycosides of flavononols include, for example, astilbin, etc. Examples of salts of flavononols may be salts acceptable as foods, pharmaceuticals, quasi-drugs or cosmetics, for example, alkali metal salts such as sodium salts and potassium salts, alkaline earth metal salts such as magnesium salts and calcium salts, ammonium salts, etc.

[0028] In this specification, flavone refers to a compound having a flavone skeleton. The flavone may be, for example, a compound represented by the following general formula (4). In general formula (4), R 40 , R 41 , R 42 , R 43 , R 44 , R 45 , R 46 , R 47 and R 48is, independently of each other, a hydrogen atom, a hydroxyl group (-OH) or a methoxy group (-OCH 3 ). Examples of flavones include, for example, nobilitin (R 42 , R 43 , R 45 , R 46 , R 47 and R 48 : methoxy group, R 40 , R 41 and R 44 : hydrogen atom), luteolin (R 41 , R 42 , R 45 and R 47 : hydroxyl group, R 40 , R 43 , R 44 , R 46 and R 48 : hydrogen atom), apigenin (R 42 , R 45 and R 47 : hydroxyl group, R 40 , R 41 , R 43 , R 44 , R 46 and R 48 : hydrogen atom), etc.

[0029]

Chemical formula

[0030] Examples of flavone glycosides include, for example, orientin, sinaroside, apiin, apigetrin, vitexin, leucoanthocyanidin, diosmin, etc. Examples of flavone salts may be salts acceptable as foods, pharmaceuticals, quasi-drugs or cosmetics, for example, alkali metal salts such as sodium salts and potassium salts, alkaline earth metal salts such as magnesium salts and calcium salts, ammonium salts, etc.

[0031] In this specification, flavanone refers to a compound having a flavanone skeleton. The flavanone may be, for example, a compound represented by the following general formula (5). In general formula (5), R 50 , R 51, R 52 , R 53 , R 54 , R 55 , R 56 , R 57 and R 58 are each independently a hydrogen atom, a hydroxyl group (-OH) or a methoxy group (-OCH 3 ). Examples of flavanones include hesperetin (R 51 , R 55 and R 57 : hydroxyl group, R 52 : methoxy group, R 50 , R 53 , R 54 , R 56 and R 58 : hydrogen atom), naringenin (R 52 , R 55 and R 57 : hydroxyl group, R 50 , R 51 , R 53 , R 54 , R 56 and R 58 : hydrogen atom), etc.

[0032]

Chemical formula

[0033] Examples of flavanone glycosides include hesperidin, narirutin, naringin, eriocitrin, etc. Examples of flavanone salts may be salts acceptable as foods, pharmaceuticals, quasi-drugs or cosmetics, for example, alkali metal salts such as sodium salts and potassium salts, alkaline earth metal salts such as magnesium salts and calcium salts, ammonium salts, etc.

[0034] In this specification, flavonol refers to a compound having a flavonol skeleton. The flavonol may be, for example, a compound represented by the following general formula (6). In general formula (6), R 60 , R 61 , R 62 , R 63 , R 64 , R65 , R 66 , R 67 and R 68 each independently represents a hydrogen atom, a hydroxyl group (-OH) or a methoxy group (-OCH 3 ). Examples of flavonols include myricetin (R 61 , R 62 , R 63 , R 65 and R 67 : hydroxyl group, R 60 , R 64 , R 66 and R 68 : hydrogen atom), quercetagetin (R 62 , R 63 , R 65 , R 66 and R 67 : hydroxyl group, R 60 , R 61 , R 64 and R 68 : hydrogen atom), fisetin (R 62 , R 63 and R 67 : hydroxyl group, R 60 , R 61 , R 64 , R 65 , R 66 and R 68 : hydrogen atom), morin (R 60 , R 62 , R 65 and R 67 : hydroxyl group, R 61 , R 63 , R 64 , R 66 and R 68 : hydrogen atom), quercetin (R 61 , R 62 , R 65 and R 67 : hydroxyl group, R 60 , R 63 , R 64 , R 66 and R 68 : hydrogen atom), kaempferol (R 62 , R 65 and R 67 : hydroxyl group, R 60 , R61 , R 63 , R 64 , R 66 and R 68 : a hydrogen atom), gossypetin (R 61 , R 62 , R 65 , R 67 and R 68 : a hydroxyl group, R 60 , R 63 , R 64 and R 66 : a hydrogen atom), etc. may be mentioned.

[0035]

Chemical formula

[0036] Examples of flavonol glycosides include myricitrin, quercetagetin-6-O-β-D-glucopyranoside, morin-3-O-arabinoside, rutin, quercitrin, hyperoside, astragalin, kaempferitrin, etc. Examples of flavonol salts may be salts acceptable as foods, pharmaceuticals, quasi-drugs or cosmetics, such as alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as magnesium salt and calcium salt, ammonium salt, etc.

[0037] In this specification, chalcone refers to a compound having a chalcone skeleton or a dihydrochalcone skeleton. Chalcone may be, for example, a compound represented by the following general formula (7) or general formula (8). In general formula (7) and general formula (8), R 70 , R 71 , R 72 , R 73 , R 74 , R 75 , R 76 , R 77 , R 78 , R 79 , R 80 , R 81 , R 82 , R 83 , R 84 , R 85 , R 86 , R87 , R 88 , R 89 , R 90 , R 91 and R 92 are each independently a hydrogen atom, a hydroxyl group (-OH), a methoxy group (-OCH 3 ), or a dimethylallyl group (-CH 2 -CH=C(CH 3 ) 2 ). Examples of chalcones include isoliquiritigenin (in general formula (7), R 72 , R 77 and R 79 : hydroxyl group, R 70 , R 71 , R 73 , R 74 , R 75 , R 76 and R 78 : hydrogen atom), phloretin (in general formula (8), R 82 , R 87 , R 89 and R 91 : hydroxyl group, R 80 , R 81 , R 83 , R 84 , R 85 , R 86 , R 88 , R 90 and R 92 : hydrogen atom), naringenin chalcone (in general formula (7), R 72 , R 75 , R 77 and R 79 : hydroxyl group, R 70 , R 71 , R 73 , R 74 , R 76 and R 78 : hydrogen atom), xanthohumol (in general formula (7), R 72 , R 77 and R 79 : hydroxyl group, R 75 : methoxy group, R 78 : dimethylallyl group, R 70 , R 71 , R 73 , R 74 and R76 : Examples include a hydrogen atom).

[0038]

Chem.

[0039]

Chem.

[0040] Examples of glycosides of chalcone include phloridzin and the like. The salts of chalcone may be salts acceptable as foods, pharmaceuticals, quasi-drugs or cosmetics, and examples thereof may include alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as magnesium salt and calcium salt, ammonium salt and the like.

[0041] In the present specification, catechins refer to compounds having a catechin skeleton. Catechins may be, for example, compounds represented by the following general formula (9). In general formula (9), R 100 represents a hydrogen atom or a hydroxyl group, and R 101 represents a hydrogen atom or a galloyl group. Examples of catechins include catechin (R 100 , R 101 : hydrogen atom, (2R,3S) and (2S,3R)), epicatechin (R 100 , R 101 : hydrogen atom, (2R,3R) and (2S,3S)), gallocatechin (R 100 : hydroxyl group, R 101 : hydrogen atom, (2R,3S) and (2S,3R)), epigallocatechin (R 100 : hydroxyl group, R 101 : hydrogen atom, (2R,3R) and (2S,3S)), catechin gallate (R 100 : hydrogen atom, R 101 : galloyl group, (2R,3S) and (2S,3R)), epicatechin gallate (R 100 : hydrogen atom, R 101 : galloyl group, (2R,3R) and (2S,3S)), gallocatechin gallate (R100 : Hydroxyl group, R 101 : Galloyl group, (2R,3S) and (2S,3R)), epigallocatechin gallate (R 100 : Hydroxyl group, R 101 : Galloyl group, (2R,3R) and (2S,3S)), etc. may be mentioned.

[0042]

Chemical formula

[0043] As salts of catechins, any salts acceptable as foods, pharmaceuticals, quasi-drugs or cosmetics may be used. For example, alkali metal salts such as sodium salts and potassium salts, alkaline earth metal salts such as magnesium salts and calcium salts, ammonium salts, etc. may be used.

[0044] Among the above-mentioned flavonoids, some may have stereoisomers. Unless otherwise specified, all possible stereoisomers are included in the scope of the present invention.

[0045] The body odor-causing substance secretion inhibitor according to the present embodiment may contain one kind of flavonoids alone, or may contain two or more kinds in combination.

[0046] The body odor-causing substance secretion inhibitor according to the present embodiment may be in any form such as solid (for example, powder), liquid (water-soluble or fat-soluble solution or suspension), paste, etc. Further, the body odor-causing substance secretion inhibitor according to the present embodiment may be in any dosage form such as tablets (orally disintegrating tablets, chewable tablets, film-coated tablets, etc.), capsules, powders, granules, liquids (syrups, jelly agents, etc.), ointments, plasters, etc.

[0047] The body odor-causing substance secretion inhibitor according to the present embodiment may consist only of flavonoids as the active ingredient, or may contain, in addition to the active ingredient, other ingredients acceptable for foods, pharmaceuticals, quasi-drugs or cosmetics according to the specific form of the body odor-causing substance secretion inhibitor.

[0048] Examples of other components include, for example, excipients, binders, lubricants, disintegrants, emulsifiers, surfactants, bases, solubilizing agents, suspending agents, etc., as well as coloring agents, fragrances, sweeteners, bittering agents, acidulants, preservatives, antifungal agents, antioxidants, emulsifiers, pH adjusters, thickening stabilizers, etc.

[0049] For example, examples of excipients include lactose, sucrose, starch, dextrin, etc. Examples of binders include polyvinyl alcohol, gum arabic, tragacanth, gelatin, hydroxypropyl methylcellulose, hydroxypropyl cellulose, sodium carboxymethylcellulose, polyvinyl pyrrolidone, etc. Examples of lubricants include magnesium stearate, calcium stearate, talc, etc. Examples of disintegrants include crystalline cellulose, agar, gelatin, calcium carbonate, sodium bicarbonate, dextrin, etc. Examples of emulsifiers or surfactants include Tween60, Tween80, Span80, glyceryl monostearate, etc. Examples of bases include cetostearyl alcohol, lanolin, polyethylene glycol, rice bran oil, fish oil (DHA, EPA, etc.), olive oil, etc. Examples of solubilizing agents include polyethylene glycol, propylene glycol, sodium carbonate, sodium citrate, Tween80, etc. Examples of suspending agents include Tween60, Tween80, Span80, glyceryl monostearate, polyvinyl alcohol, polyvinyl pyrrolidone, methylcellulose, hydroxymethylcellulose, sodium alginate, etc.

[0050] For example, examples of coloring agents include beta-carotene, caramel, or red yeast rice pigment, etc. Examples of fragrances include ethyl acetoacetate, acetophenone, anisaldehyde, etc. Examples of sweeteners include saccharides or sugar alcohols, stevia, or aspartame, etc. Examples of bitter agents include caffeine, etc. Examples of salt seasonings include table salt, or potassium chloride, etc. Examples of acidulants include acetic acid, lactic acid, or gluconic acid, etc. Examples of preservatives include methyl paraben, propyl paraben, etc. Examples of antifungal agents include imazalil, orthophenylphenol, thiabendazole, fludioxonil, etc. Examples of antioxidants include tocopherol, or tea extract, etc. Examples of emulsifiers include glycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, glycerin organic acid fatty acid ester, polyglycerin fatty acid ester, calcium stearoyl lactate, sodium stearoyl lactate, polyoxyethylene sorbitan fatty acid ester, etc. Examples of pH adjusters include citric acid, malic acid, phosphoric acid, etc. Examples of thickening stabilizers include locust bean gum, carrageenan, alginic acids, pectin, xanthan gum, crystalline cellulose, carboxymethyl cellulose, methyl cellulose, agar, glucomannan, gelatin, starch, or chemical modified starch, etc.

[0051] The body odor-causing substance secretion inhibitor according to this embodiment can be prepared, for example, as a food composition (including beverages and foods), a pharmaceutical composition, a quasi-drug composition, or a cosmetic composition. That is, as one embodiment of the present invention, there are provided a food composition (beverages and foods) for inhibiting the secretion of body odor-causing substances containing flavonoids as an active ingredient, a pharmaceutical composition for inhibiting the secretion of body odor-causing substances, a quasi-drug composition for inhibiting the secretion of body odor-causing substances, and a cosmetic composition for inhibiting the secretion of body odor-causing substances.

[0052] Specific forms of beverages include, for example, water, soft drinks, fruit juices, carbonated beverages, milk beverages, alcoholic beverages, sports drinks, nutritional drinks, etc. Specific forms of foods include breads, noodles, soups, rice, tofu, dairy products, soy sauce, miso, confectioneries, etc. Further, food compositions include, for example, health foods, foods with functional claims, foods for special dietary uses, dietary supplements, supplements, and foods for specified health uses, etc.

[0053] The pharmaceutical composition, quasi-drug composition, or cosmetic composition for suppressing the secretion of body odor-causing substances according to the present embodiment can be administered in any dosage form. Upon administration, the active ingredient can be mixed with a solid or liquid non-toxic pharmaceutical carrier suitable for administration methods such as oral administration, transdermal administration, injection, etc., and administered in the form of a conventional pharmaceutical preparation, quasi-drug preparation, or cosmetic preparation.

[0054] When used as a pharmaceutical composition, quasi-drug composition, or cosmetic composition for orally administering the pharmaceutical composition, quasi-drug composition, or cosmetic composition for suppressing the secretion of body odor-causing substances according to the present embodiment, the dosage form is not particularly limited, and examples include tablets such as orally disintegrating tablets, chewable tablets, effervescent tablets, dispersible tablets, soluble tablets, troches, powders, suspensions, emulsions, syrups, etc.

[0055] When the pharmaceutical composition, quasi-drug composition, or cosmetic composition for suppressing the secretion of body odor-causing substances according to the present embodiment is used as a topical skin composition, for example, dosage forms such as creams, lotions, sprays, sticks, etc. can be adopted. In particular, when the cosmetic composition for suppressing the secretion of body odor-causing substances according to the present embodiment is used as a topical skin composition, it can be prepared, for example, as an antiperspirant deodorant lotion, lotion, deodorant lotion, beauty lotion, emulsion, hand soap, deodorant powder spray, roll-on, etc.

[0056] Since the body odor-causing substance secretion inhibitor according to this embodiment can be easily ingested on a daily basis, it is preferably a food composition (a food composition for suppressing the secretion of body odor-causing substances). As the form of the food composition for suppressing the secretion of body odor-causing substances according to this embodiment, those described above can be mentioned, and from the viewpoint of being easily ingested on a daily basis, it is preferably a beverage (a beverage for suppressing the secretion of body odor-causing substances).

[0057] The food composition for suppressing the secretion of body odor-causing substances according to this embodiment may be labeled, for example, with indications such as "For those who are concerned about body odor" and "Suppress the odor that concerns you from within the body".

[0058] The content of the active ingredient in the body odor-causing substance secretion inhibitor according to this embodiment can be appropriately set according to the specific form of the body odor-causing substance secretion inhibitor (for example, form, usage, dosage, etc.).

[0059] For example, when the body odor-causing substance secretion inhibitor according to this embodiment is administered orally (ingested orally), the active ingredient may be used such that 1 mg or more is administered orally (ingested orally) per day. By administering 1 mg or more of the active ingredient orally (ingested orally) per day, a sufficient body odor-causing substance secretion inhibitory effect can be obtained. For example, when the body odor-causing substance secretion inhibitor according to this embodiment is used such that it is administered orally (ingested orally) three times a day, by containing 0.34 mg or more of the active ingredient in the body odor-causing substance secretion inhibitor, the oral administration (oral ingestion) amount per day becomes 1 mg or more.

[0060] The above daily oral administration (oral intake) amount (amount of active ingredient) may be, for example, 2 mg or more, 3 mg or more, 4 mg or more, 5 mg or more, 6 mg or more, 7 mg or more, 8 mg or more, 9 mg or more, or 10 mg or more. Also, from the perspective of the effect of suppressing the secretion of body odor-causing substances, there is no particular limitation on the upper limit of the above-mentioned daily oral administration (oral intake) amount. However, from the perspective of reducing manufacturing costs, it may be, for example, 1000 mg or less, 900 mg or less, 800 mg or less, 700 mg or less, 600 mg or less, 500 mg or less, 400 mg or less, 300 mg or less, 200 mg or less, or 100 mg or less. Further, the above-mentioned daily oral administration (oral intake) amount is preferably the amount per 60 kg of body weight. However, when there are publicly determined intake guidelines and upper limits depending on the type of active ingredient, it is desirable to follow such guidelines.

[0061] The content of the active ingredient in the body odor-causing substance secretion inhibitor according to this embodiment is appropriately set according to the specific form of the body odor-causing substance secretion inhibitor (for example, form, usage, dosage, etc.). However, in one aspect, the content of the active ingredient in the body odor-causing substance secretion inhibitor according to this embodiment, based on the total amount of the body odor-causing substance secretion inhibitor, may be, for example, 2 mg or more, 3 mg or more, 4 mg or more, 5 mg or more, 6 mg or more, 7 mg or more, 8 mg or more, 9 mg or more, or 10 mg or more. Thereby, the above-mentioned daily oral administration (oral intake) amount can be easily achieved. The upper limit of the content of the active ingredient in the body odor-causing substance secretion inhibitor according to this embodiment may be, for example, 1000 mg or less, 900 mg or less, 800 mg or less, 700 mg or less, 600 mg or less, 500 mg or less, 400 mg or less, 300 mg or less, 200 mg or less, or 100 mg or less.

[0062] The body odor-causing substance secretion inhibitor according to this embodiment may be administered (ingested) to humans or non-human mammals.

[0063] The body odor-causing substance secretion inhibitor according to this embodiment may be administered orally (orally ingested) or parenterally, but oral administration (oral ingestion) is preferred. The body odor-causing substance secretion inhibitor according to this embodiment may be administered (ingested) once a day or divided into multiple times a day.

[0064] The body odor-causing substance secretion inhibitor according to this embodiment can be obtained, for example, by blending flavonoids as an active ingredient according to its specific form (for example, form, usage, dosage, etc.). At this time, as the flavonoids as the active ingredient, flavonoids themselves may be used, or a composition containing flavonoids (for example, a plant extract such as soybeans) may be used.

[0065] The body odor-causing substance secretion inhibitor according to this embodiment can inhibit the transport activity of ABCC11 and suppress the uptake of body odor-causing substances into vesicles in the secretory cells of apocrine glands due to the action of flavonoids, so that the secretion of body odor-causing substances can be suppressed at the source. Therefore, the body odor-causing substance secretion inhibitor according to this embodiment can be used, for example, for the suppression, prevention or improvement of body odors such as fatigue odor, stress odor, aging odor, axillary osmidrosis, etc.

Example

[0066] Hereinafter, the present invention will be described more specifically based on examples. However, the present invention is not limited by the following examples.

[0067] 〔Test Example 1: Evaluation of ABCC11 inhibitory effect〕 Membrane vesicles (inverted membrane vesicles. ABCC11 is arranged to transport substrates from outside the vesicles to inside the vesicles.) were prepared from ABCC11-expressing cells and used for the evaluation of the ABCC11 inhibitory effect.

[0068] (1) Preparation of soybean extract 100 g of ground soybeans were added with 1000 g of water, and after stirring, the solid content was removed by filtration to obtain a soybean water extract. The extract was dialyzed using a dialysis membrane (MWCO 3.5 - 5 kDa), and the external dialysis solution was collected. The external dialysis solution of the obtained soybean extract was fractionated by liquid chromatography (LC), and the fraction obtained under the following conditions was used as the soybean extract. YMC DispoPack AT 120 g, flow rate 40 mL / min Mobile phase: A: 0.2% aqueous formic acid solution, B: 0.2% formic acid - acetonitrile solution Elution conditions: B 5% (0 - 5 minutes), B 5% - 100% Gradient (5 - 25 minutes) The eluate from the elution time of 19.5 - 22.9 minutes under the above conditions was collected, dried, and the concentration was adjusted.

[0069] (2) Preparation of ABCC11-expressing cells Human embryonic kidney cell-derived 293A cells were seeded in a 15 cm dish (manufactured by Greiner), and incubated at 37 °C, 5% CO 2Cells were cultured until they reached 90 - 95% confluence under the given conditions. Polyethylenimine MAX (hereinafter referred to as "PEI - MAX") was used as the gene transfection reagent. 100 μL of PEI - MAX prepared to 1 mg / mL (pH 7.0) with sterile MilliQ was taken per dish, diluted with high - glucose DMEM medium containing 1000 μL of 1×MEM Non - Essential Amino Acids Solution (NEAA) and 1×L - Glutamine (L - Gln) (hereinafter referred to as "Serum - Free DMEM"), and then left standing at room temperature for 5 minutes (hereinafter referred to as "PEI - Free DMEM"). 20 μg per dish (for example, 100 μL if it is a 200 ng / μL plasmid solution) of the human ABCC11 (NCBI accession; NM_033151) expression vector and the control vector (pcDNA3.1) were diluted with 1000 μL of Serum - Free DMEM and left standing for 5 minutes (hereinafter referred to as "Plasmid - Free DMEM"). Plasmid - Free DMEM and PEI - Free DMEM were mixed, left standing at room temperature for 20 minutes or more, and then 2200 μL per dish was added to 293A cells. After 8 hours, the medium was replaced with DMEM, and the cells were harvested 2 days after transfection. The cells were harvested by washing the cells with 5 mL / dish of sterile PBS to remove the medium, then scraping the cells off with a cell scraper and transferring them to a 50 mL Falcon tube. After centrifugation at 1500 rpm for 5 minutes, the supernatant was removed, PBS was added again for washing, and centrifugation was performed at 1500 rpm for 5 minutes. The supernatant was removed and stored at - 80°C until membrane vesicle preparation.

[0070] (3) Preparation of membrane vesicles (2) The ABCC11 - expressing cells prepared in (2) were expanded and lysed, and ultracentrifuged under 4°C conditions. The supernatant was discarded, and after completely removing the water, the pellet was resuspended with an isotonic buffer, and the cells were completely lysed using a Dounce - type homogenizer. The cell suspension was layered on 38% Sucrose and ultracentrifuged again.

[0071] After sucking out the upper part of the aqueous layer after ultracentrifugation, the membrane proteins floating on the intermediate interface were collected, and isotonic buffer was added and washed by ultracentrifugation under 4°C conditions. After washing, after removing the supernatant, isotonic buffer was added and pipetted and mixed, and then syringe homogenized to obtain membrane vesicles. The membrane vesicles were cryopreserved at -80°C until use. Also, membrane vesicles were prepared from control cells by the same procedure and used as control membrane vesicles.

[0072] (4) Evaluation of ABCC11 inhibitory effect As a substrate of ABCC11 (substance transported by ABCC11), 3 [³H] estrone sulfate (E 1 S) or 3 [³H] dehydroepiandrosterone sulfate (DHEAS) (both manufactured by Perkin-Elmer Japan) was used.

[0073] ]> The reaction solution was incubated for 5 minutes under the following 4 types of conditions, and the radioactivity (number of disintegrations) derived from the substrate incorporated into the membrane vesicles was measured. (a) In the reaction solution, control membrane vesicles 5.0 or 7.5 μg / 20 μL, without ATP, substrate 100 nM (Mock ATP (-)). (i) In the reaction solution, control membrane vesicles 5.0 or 7.5 μg / 20 μL, ATP 5 mM, substrate 100 nM (Mock ATP (+)). (u) In the reaction solution, membrane vesicles 5.0 or 7.5 μg / 20 μL, without ATP, substrate 100 nM (ABCC11 ATP (-)). (e) In the reaction solution, membrane vesicles 5.0 or 7.5 μg / 20 μL, ATP 5 mM, substrate 100 nM (ABCC11 ATP (+)).

[0074] The ATP-dependent transport activity in the control membrane vesicles (= radioactivity of Mock ATP (+) - radioactivity of Mock ATP (-)) was calculated from the measured radioactivity. Then, based on that, the ABCC11-dependent transport activity (= ABCC11 ATP (+) - ABCC11 ATP (-) - ATP-dependent transport activity in the control membrane vesicles) was calculated.

[0075] In addition, the soybean extract prepared in (1) was added to the reaction solution so that the final concentration was 100 ppm (100 mg / L), and measurement was performed under the same conditions. Subsequently, according to the following formula, the inhibition rate of the transport activity of ABCC11 by the soybean extract was calculated. Inhibition rate = {1 - (ABCC11-dependent transport activity when soybean extract is added / ABCC11-dependent transport activity when soybean extract is not added)} × 100 (%)

[0076] The results are shown in Table 1.

Table 1

[0077] As shown in Table 1, an ABCC11 inhibitory effect (inhibitory effect on the transport activity of ABCC11) was observed in the soybean extract. Also, in this evaluation system, there was no significant difference in the measurement results of the inhibition rate of the transport activity of ABCC11 due to the difference in the substrate.

[0078] 〔Test Example 2: Evaluation of the ABCC11 inhibitory effect of flavonoids〕 (1) Preparation of ABCC11-expressing cells (Preparation of adenovirus for human ABCC11 expression) The full-length amino acid coding sequence of human ABCC11 was cloned into the Gateway pDONR221 vector by BP cloning to obtain an entry clone. An in vitro recombination reaction was performed between the obtained entry clone and the pAD / CMV / V5-DEST (registered trademark) Gateway (registered trademark) vector to obtain a vector for producing adenovirus for ABCC11 expression. The obtained recombinant plasmid and the control plasmid without the ABCC11 gene were each purified and linearized by treatment with the restriction enzyme PacI at 37°C for 2 hours. The linearized plasmids were each transfected into 293A cells derived from human fetal kidney, which are packaging cells, and cultured for several weeks to produce ABCC11-expressing adenovirus or control adenovirus. Each adenovirus contained in the cultured cells and culture supernatant was recovered and roughly purified, and the adenovirus was amplified by infecting fresh 293A cells. After repeating the amplification, each recombinant adenovirus was purified using cesium chloride density gradient ultracentrifugation and stored at -80°C until use.

[0079] (Preparation of ABCC11-expressing cells) 293A cells were seeded in a 10 cm dish (manufactured by Greiner) at a cell density of 3.0×10 6 cells / dish and cultured at 37°C under 5% CO 2 conditions for 24 hours. The cells were infected with the ABCC11 expression vector and the control vector (EGFP-expressing adenovirus) at 2.5 MOI (multiplicity of infection) / dish, and the cells were harvested 48 hours later. The cells were harvested by washing the cells with 5 mL / dish of sterile PBS after removing the medium, then scraping the cells off with a cell scraper and transferring them to a 50 mL Falcon tube. After centrifugation at 1500 rpm for 5 minutes, the supernatant was removed, PBS was added again for washing, and centrifugation was performed at 1500 rpm for 5 minutes. The supernatant was removed and stored at -80°C until membrane vesicle preparation.

[0080] (2) Preparation of membrane vesicles Using the ABCC11-expressing cells prepared in (1), membrane vesicles were prepared in the same procedure as in Test Example 1. Control membrane vesicles were also prepared in the same procedure.

[0081] (3) Evaluation of the ABCC11 inhibitory effect of flavonoids As flavonoids, the compounds shown in Table 2 were subjected to evaluation. As a substrate, 3 [³H] dehydroepiandrosterone sulfate (DHEAS) (manufactured by Perkin-Elmer Japan) was used. The reaction solution was incubated for 5 minutes under the following four conditions, and the radioactivity (number of disintegrations) derived from the substrate incorporated into the membrane vesicles was measured. (a) In the reaction solution, 10.0 μg / 20 μL of control membrane vesicles, without ATP, 100 nM of substrate (Mock ATP (-)). (i) In the reaction solution, 10.0 μg / 20 μL of control membrane vesicles, 5 mM of ATP, 100 nM of substrate (Mock ATP (+)). (u) In the reaction solution, 10.0 μg / 20 μL of membrane vesicles, without ATP, 100 nM of substrate (ABCC11 ATP (-)). (e) In the reaction solution, 10.0 μg / 20 μL of membrane vesicles, 5 mM of ATP, 100 nM of substrate (ABCC11 ATP (+)).

[0082] From the measured radioactivity, the ATP-dependent transport activity in the control membrane vesicles (= radioactivity of Mock ATP (+) - radioactivity of Mock ATP (-)) was calculated. Then, based on that, the ABCC11-dependent transport activity (= ABCC11 ATP (+) - ABCC11 ATP (-) - ATP-dependent transport activity in the control membrane vesicles) was calculated.

[0083] Also, flavonoids were added to the reaction solution to a final concentration of 100 ppm (100 mg / L), and measurements were performed under the same conditions. Then, according to the following formula, the inhibition rate of the transport activity of ABCC11 by flavonoids was calculated. Each flavonoid was measured with n = 3. Inhibition rate = {1 - (ABCC11-dependent transport activity when flavonoids are added / ABCC11-dependent transport activity when flavonoids are not added)} × 100 (%)

[0084] The results are shown in Table 2.

Table 2

[0085] As shown in Table 2, an ABCC11 inhibitory effect (inhibitory effect on the transport activity of ABCC11) was observed for flavonoids.

Claims

1. An axillary osmidrosis causative substance secretion inhibitor containing flavonoids as an active ingredient (excluding evening primrose seed extract and perilla seed extract).

2. The axillary osmidrosis causative substance secretion inhibitor according to Claim 1, wherein the flavonoids are at least one selected from the group consisting of isoflavonoids, flavanonols, flavones, flavanones, flavonols, chalcones, catechins and their glycosides, and salts thereof.

3. A food composition for inhibiting the secretion of axillary osmidrosis causative substances containing flavonoids as an active ingredient (excluding evening primrose seed extract and perilla seed extract).

4. A pharmaceutical composition for inhibiting the secretion of axillary osmidrosis causative substances containing flavonoids as an active ingredient (excluding evening primrose seed extract and perilla seed extract), a quasi-drug composition for inhibiting the secretion of axillary osmidrosis causative substances (excluding evening primrose seed extract and perilla seed extract), or a cosmetic composition for inhibiting the secretion of axillary osmidrosis causative substances (excluding evening primrose seed extract and perilla seed extract).

Images