Agent for inhibiting secretion of body odor-causing substance

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.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an agent for suppressing the secretion of substances that cause body odor. [Background technology]

[0002] ABCC11, a type of ATP-Binding Cassette (ABC) transporter, is a protein that is expressed in apocrine glands and transports various substrates. There are two types of ABCC11: wild type, in which the 180th amino acid is Gly, and mutant type, in which this is mutated to Arg. In addition, wild type ABCC11 / mutant ABCC11 determine the human earwax type, resulting in wet / dry phenotypes, respectively.

[0003] In recent years, the relationship between wild-type ABCC11 / mutant ABCC11 and body odor (e.g., axillary odor) has been attracting attention. For example, Non-Patent Document 1 describes that in the secretory cells of the apocrine gland, ABCC11 takes up substances causing body odor into vesicles, and the vesicles that have taken up the substances causing body odor leave the secretory cells and move from the dermis to the epidermis, releasing the substances causing body odor onto the skin surface, which are then converted into body odor components by resident skin bacteria. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] Practical Manual for the Treatment of Axillary Odor and Hyperhidrosis, All Japan Hospital Publishing, March 2012 Summary of the Invention [Problem to be solved by the invention]

[0005] Currently, the mainstream body odor care products are those that apply methods to kill bacteria that normally reside on the skin, or methods to suppress the activity of bacteria that normally reside on the skin by suppressing the secretion of sweat (moisture), etc. Almost nothing is known that can suppress the secretion of the substances that cause body odor themselves.

[0006] The present inventors have found that flavonoids have the effect of inhibiting the transport activity of ABCC11. It is believed that by inhibiting the transport activity of ABCC11, the uptake of body odor-causing substances into vesicles in secretory cells of the apocrine gland can be inhibited, and therefore the secretion of body odor-causing substances can be inhibited from the root. The present invention is based on this novel finding, and aims to provide a novel agent for inhibiting the secretion of body odor-causing substances. [Means for solving the problem]

[0007] The present invention relates to an agent for suppressing the secretion of substances that cause body odor, which contains flavonoids as active ingredients.

[0008] The body odor-causing substance secretion inhibitor of the present invention contains flavonoids as active ingredients, and the flavonoids have the effect of inhibiting the transport activity of ABCC11, thereby suppressing the uptake of body odor-causing substances into vesicles in the secretory cells of the apocrine glands, and suppressing the secretion of body odor-causing substances from the apocrine glands to the epidermis.

[0009] The flavonoid may be at least one selected from the group consisting of isoflavonoids, flavanonol, flavones, flavanones, flavonols, chalcones, catechins, glycosides thereof, and salts thereof, thereby making the above-mentioned effects more pronounced.

[0010] The present invention also relates to a food composition for suppressing the secretion of substances that cause body odor, which contains flavonoids as active ingredients.

[0011] The present invention further relates to a pharmaceutical composition, a quasi-drug composition, or a cosmetic composition for suppressing the secretion of substances that cause body odor, which contains flavonoids as active ingredients. Effect of the Invention

[0012] According to the present invention, a novel agent for suppressing the secretion of substances that cause body odor can be provided. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0013] Hereinafter, an embodiment of the present invention will be described in detail. However, the present invention is not limited to the following embodiment.

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

[0015] The body odor-causing substance secretion inhibitor according to this embodiment has an effect of inhibiting the transport activity of ABCC11 (transporter), and therefore can inhibit the uptake of body odor-causing substances into vesicles in secretory cells of the apocrine gland, and can inhibit the secretion of body odor-causing substances from the apocrine gland to the epidermis. In this specification, "body odor-causing substances" includes substances that themselves have an odor and are one of the causes of body odor, and substances that are converted into odorous substances by the action of resident skin bacteria and are one of the causes of body odor.

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

[0017] Examples of flavonoids include isoflavonoids, flavanonols, flavones, flavanones, flavonols, chalcones, catechins, and glycosides thereof, as well as salts thereof.

[0018] As used herein, isoflavonoids refer to isoflavones and isoflavans, as well as metabolites thereof.

[0019] In the present 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 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 represents a hydrogen atom, a hydroxyl group (-OH), or a methoxy group (-OCH3). 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), etc.

[0020] [ka]

[0021] In the present 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 general formula (2), R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 and R 29Each independently represents a hydrogen atom, a hydroxyl group (-OH), or a methoxy group (-OCH3). Examples of isoflavan 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] [ka]

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

[0024] Examples of glycosides of isoflavonoids include puerarin, daidzin, etc. Salts of isoflavonoids may be any salt acceptable for use as food, medicine, quasi-drug, or cosmetic, and may be, for example, 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, flavanonol refers to a compound having a flavanonol skeleton. The flavanonol may be, for example, a compound represented by the following formula (3). In general formula (3), R 30 , R 31 , R 32 , R 33 , R 34 , R 35 , R 36 , R37 and R 38 Each independently represents a hydrogen atom, a hydroxyl group (-OH), or a methoxy group (-OCH3). Examples of flavanonols include 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] [ka]

[0027] An example of a glycoside of flavanonol is astilbin, etc. The salt of flavanonol may be any salt acceptable for use as a food, pharmaceutical, quasi-drug, or cosmetic, and may be, for example, an alkali metal salt such as a sodium salt or a potassium salt, an alkaline earth metal salt such as a magnesium salt or a calcium salt, or an ammonium salt.

[0028] In this specification, flavone refers to a compound having a flavone skeleton. For example, flavone may be 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 48Each independently represents a hydrogen atom, a hydroxyl group (-OH), or a methoxy group (-OCH3). Examples of flavones include nobiletin (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] [ka]

[0030] Examples of glycosides of flavone include orientin, cynalloside, apiin, apigetrin, vitexin, rhoifolin, diosmin, etc. Examples of salts of flavone include salts that are acceptable for use as foods, medicines, quasi-drugs, or cosmetics, and may be, 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 , R52 , R 53 , R 54 , R 55 , R 56 , R 57 and R 58 Each independently represents a hydrogen atom, a hydroxyl group (-OH), or a methoxy group (-OCH3). 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] [ka]

[0033] Examples of glycosides of flavanone include hesperidin, narirutin, naringin, eriocitrin, etc. The salts of flavanone may be any salt acceptable for use as foods, medicines, quasi-drugs, or cosmetics, and may be, 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 , R 65 , R66 , R 67 and R 68 Each independently represents a hydrogen atom, a hydroxyl group (-OH), or a methoxy group (-OCH3). 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 , R 61 , R 63 , R64 , R 66 and R 68 : hydrogen atom), gossypetin (R 61 , R 62 , R 65 , R 67 and R 68 : Hydroxyl group, R 60 , R 63 , R 64 and R 66 : hydrogen atom), etc.

[0035] [ka]

[0036] Examples of glycosides of flavonols include myricitrin, quercetagetin-6-O-β-D-glucopyranoside, morin-3-O-arabinoside, rutin, quercitrin, hyperoside, astragalin, kaempferitrin, etc. Examples of salts of flavonols include salts that are acceptable for use as foods, medicines, quasi-drugs, or cosmetics, and may be, 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.

[0037] In the present 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 , R 87 , R 88 , R89 , R 90 , R 91 and R 92 Each independently represents a hydrogen atom, a hydroxyl group (-OH), a methoxy group (-OCH3), or a dimethylallyl group (-CH2-CH=C(CH3)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 R 76 : hydrogen atom), etc.

[0038] [ka]

[0039] [ka]

[0040] An example of a glycoside of chalcone is phloridzin, etc. The salt of chalcone may be any salt acceptable for use as a food, pharmaceutical, quasi-drug, or cosmetic, and may be, for example, an alkali metal salt such as a sodium salt or a potassium salt, an alkaline earth metal salt such as a magnesium salt or a calcium salt, or an ammonium salt.

[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, 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 (R 100 : Hydroxyl group, R 101 : Galloyl group, (2R,3S) and (2S,3R)), epigallocatechin gallate (R 100: Hydroxyl group, R 101 : galloyl groups, (2R,3R) and (2S,3S)).

[0042] [ka]

[0043] The salt of catechins may be any salt acceptable for use as a food, pharmaceutical, quasi-drug, or cosmetic, and may be, for example, an alkali metal salt such as sodium salt or potassium salt, an alkaline earth metal salt such as magnesium salt or calcium salt, or an ammonium salt.

[0044] Some of the flavonoids described above may exist in stereoisomers, and unless otherwise specified, all possible stereoisomers are within the scope of the present invention.

[0045] The body odor-causing substance secretion inhibitor according to this embodiment may contain one type of flavonoid alone or two or more types in combination.

[0046] The body odor causative substance secretion inhibitor according to this embodiment may be in any form, such as a solid (e.g., powder), liquid (water-soluble or fat-soluble solution or suspension), paste, etc. In addition, the body odor causative substance secretion inhibitor according to this embodiment may be in any form, such as a tablet (orally disintegrating tablet, chewable tablet, film-coated tablet, etc.), capsule, powder, granule, liquid (syrup, jelly, etc.), ointment, plaster, etc.

[0047] The body odor-causing substance secretion inhibitor of this embodiment may consist only of flavonoids, which are the active ingredient, or, depending on the specific form of the body odor-causing substance secretion inhibitor, may contain, in addition to the active ingredient, other ingredients that are acceptable for use in, for example, foods, medicines, quasi-drugs, or cosmetics.

[0048] Other components include, for example, excipients, binders, lubricants, disintegrants, emulsifiers, surfactants, bases, solubilizers, suspending agents, etc., as well as colorants, flavorings, sweeteners, bittering agents, acidulants, preservatives, anti-mold agents, antioxidants, emulsifiers, pH adjusters, thickening stabilizers, etc.

[0049] For example, excipients include lactose, sucrose, starch, dextrin, etc. Binders include polyvinyl alcohol, gum arabic, tragacanth, gelatin, hydroxypropylmethylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, etc. Lubricants include magnesium stearate, calcium stearate, talc, etc. Disintegrants include crystalline cellulose, agar, gelatin, calcium carbonate, sodium bicarbonate, dextrin, etc. Emulsifiers or surfactants include Tween 60, Tween 80, Span 80, glycerin monostearate, etc. Bases include cetostearyl alcohol, lanolin, polyethylene glycol, rice bran oil, fish oil (DHA, EPA, etc.), olive oil, etc. Dissolution aids include polyethylene glycol, propylene glycol, sodium carbonate, sodium citrate, Tween 80, etc. Suspending agents include Tween 60, Tween 80, Span 80, glyceryl monostearate, polyvinyl alcohol, polyvinylpyrrolidone, methylcellulose, hydroxymethylcellulose, sodium alginate, and the like.

[0050] Further, for example, colorants include beta-carotene, caramel, red koji coloring, and the like. Flavorings include ethyl acetoacetate, acetophenone, anisaldehyde, and the like. Sweeteners include sugars or sugar alcohols, stevia, aspartame, and the like. Bittering agents include caffeine, and the like. Salt seasonings include table salt, potassium chloride, and the like. Acidulants include acetic acid, lactic acid, gluconic acid, and the like. Preservatives include methylparaben, propylparaben, and the like. Antifungal agents include imazalil, orthophenylphenol, thiabendazole, fludioxonil, and the like. Antioxidants include tocopherol, tea extract, and the like. Emulsifiers include glycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, propylene glycol fatty acid esters, glycerin organic acid fatty acid esters, polyglycerin fatty acid esters, calcium stearoyl lactate, sodium stearoyl lactate, polyoxyethylene sorbitan fatty acid esters, and the like. 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, and modified starch.

[0051] The inhibitor for the secretion of body odor-causing substances 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 (including beverages and foods) for suppressing the secretion of body odor-causing substances, a pharmaceutical composition for suppressing the secretion of body odor-causing substances, a quasi-drug composition for suppressing the secretion of body odor-causing substances, and a cosmetic composition for suppressing the secretion of body odor-causing substances, each of which contains flavonoids as an active ingredient.

[0052] Specific examples of beverages include water, soft drinks, fruit juices, carbonated drinks, dairy drinks, alcoholic drinks, sports drinks, and nutritional drinks. Specific examples of foods include breads, noodles, soups, rice, tofu, dairy products, soy sauce, miso paste, confectionery, and the like. Food compositions include, for example, health foods, functional foods, special dietary foods, dietary supplements, supplements, and foods for specified health uses.

[0053] The pharmaceutical composition, quasi-drug composition, or cosmetic composition for suppressing the secretion of body odor-causing substances according to this embodiment can be administered in any dosage form. When administered, 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, and injection, and administered in the form of a conventional pharmaceutical formulation, quasi-drug formulation, or cosmetic formulation.

[0054] When the pharmaceutical composition, quasi-drug composition, or cosmetic composition for suppressing the secretion of substances that cause body odor according to this embodiment is used as a pharmaceutical composition, quasi-drug composition, or cosmetic composition for oral administration, the dosage form is not particularly limited, and examples include tablets such as orally disintegrating tablets, chewable tablets, effervescent tablets, dispersible tablets, and dissolving tablets, as well as lozenges, powders, suspensions, emulsions, syrups, and the like.

[0055] Furthermore, when the pharmaceutical composition, quasi-drug composition, or cosmetic composition for suppressing the secretion of body odor-causing substances according to this embodiment is used as a composition for external application to the skin, it may be in the form of, for example, a cream, lotion, spray, stick, etc. In particular, when the cosmetic composition for suppressing the secretion of body odor-causing substances according to this embodiment is used as a composition for external application to the skin, it may be prepared as, for example, an antiperspirant deodorant lotion, a skin lotion, a deodorant skin lotion, a beauty skin lotion, an emulsion, a hand soap, a deodorant powder spray, a roll-on, etc.

[0056] The body odor causative substance secretion inhibitor according to this embodiment is preferably a food composition (food composition for suppressing the secretion of body odor causative substances) because it can be easily ingested on a daily basis. The form of the food composition for suppressing the secretion of body odor causative substances according to this embodiment can be any of those described above, and is preferably a beverage (beverage for suppressing the secretion of body odor causative substances) from the viewpoint of easy daily intake.

[0057] The food composition for suppressing the secretion of substances that cause body odor according to this embodiment may be labeled, for example, as "for those who are concerned about body odor" or "suppresses unpleasant odors 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 depending on the specific aspects of the body odor-causing substance secretion inhibitor (e.g., form, method of use, dosage, etc.).

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

[0060] The above-mentioned oral administration (oral intake) amount (amount of active ingredient) per day 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. From the viewpoint of the body odor causative substance secretion suppression effect, there is no particular limit to the upper limit of the above-mentioned oral administration (oral intake) amount per day, but from the viewpoint of reducing the manufacturing cost, 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. The above-mentioned oral administration (oral intake) amount per day is preferably an amount per 60 kg of body weight. However, if there is a publicly determined guideline or upper limit of the intake amount depending on the type of active ingredient, it is desirable to follow the guideline.

[0061] The content of the active ingredient in the body odor causative substance secretion inhibitor according to this embodiment is appropriately set according to the specific aspect of the body odor causative substance secretion inhibitor (for example, form, usage, dosage, etc.), but in one aspect, the content of the active ingredient in the body odor causative substance secretion inhibitor according to this embodiment 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 based on the total amount of the body odor causative substance secretion inhibitor. This makes it possible to easily achieve the above-mentioned daily oral administration (oral intake) amount. The upper limit of the content of the active ingredient in the body odor causative 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 causative substance secretion inhibitor according to the present embodiment may be administered orally (ingested orally) or parenterally, but is preferably administered orally (ingested orally). The body odor causative substance secretion inhibitor according to the present embodiment may be administered (ingested) once a day, or may be administered (ingested) in multiple doses a day.

[0064] The body odor causative substance secretion inhibitor according to the present embodiment can be obtained by, for example, blending flavonoids as active ingredients, depending on the specific aspect (e.g., form, method of use, dosage, etc.). In this case, as the flavonoids as active ingredients, the flavonoids themselves may be used, or a composition containing flavonoids (e.g., a plant extract such as soybean) may be used.

[0065] The body odor causative substance secretion inhibitor according to the present embodiment can inhibit the transport activity of ABCC11 by the action of flavonoids, and can inhibit the uptake of body odor causative substances into vesicles in secretory cells of apocrine glands, thereby suppressing the secretion of body odor causative substances from the root. Therefore, the body odor causative substance secretion inhibitor according to the present embodiment can be used to suppress, prevent, or improve body odors such as fatigue odor, stress odor, aging odor, and armpit odor. EXAMPLES

[0066] The present invention will be described in more detail below with reference to examples, although the present invention is not limited to the following examples.

[0067] [Test Example 1: Evaluation of ABCC11 inhibitory effect] Membrane vesicles (inverted membrane vesicles, in which ABCC11 is positioned so as to transport substrates from the outside to the inside of the vesicle) were prepared from ABCC11-expressing cells and used to evaluate the inhibitory effect of ABCC11.

[0068] (1) Preparation of soybean extract 1000g of water was added to 100g of ground soybeans, stirred, and the solids were removed by filtration to obtain a soybean water extract. The extract was dialyzed using a dialysis membrane (MWCO 3.5-5kDa) and the dialysate was collected. The dialysate of the obtained soybean extract was fractionated by liquid chromatography (LC), and the fraction obtained under the following conditions was designated as the soybean extract. YMC DispoPack AT120g, flow rate 40mL / min Mobile phase: A: 0.2% formic acid in water, B: 0.2% formic acid-acetonitrile solution Elution conditions: B 5% (0~5 minutes), B 5%-100% Gradient (5~25 minutes) Under the above conditions, the eluate from elution time 19.5 to 22.9 minutes was collected, dried, and the concentration was adjusted.

[0069] (2) Preparation of ABCC11-expressing cells Human fetal kidney cell-derived 293A cells were seeded on a 15 cm dish (Greiner) and cultured at 37°C and 5% CO2 until 90-95% confluent. Polyethylenimine MAX (hereinafter referred to as "PEI-MAX") was used as the gene transfer reagent. PEI-MAX was adjusted to 1 mg / mL (pH 7.0) using sterilized MilliQ, and 100 μL was taken per dish, diluted with 1000 μL of 1×MEM Non-Essential Amino Acids Solution (NEAA) and 1×L-Glutamine (L-Gln)-containing high-glucose DMEM medium (hereinafter referred to as Serum-Free DMEM) and left to stand at room temperature for 5 minutes (hereinafter referred to as "PEI-Free DMEM"). 20μg of human ABCC11 (NCBI accession; NM_033151) expression vector and control vector (pcDNA3.1) per dish (for example, 100μL for 200ng / μL plasmid solution) were diluted with 1000μL of Serum-Free DMEM and left to stand for 5 minutes (hereinafter referred to as "Plasmid-Free DMEM"). Plasmid-Free DMEM and PEI-Free DMEM were mixed and left to stand for 20 minutes or more at room temperature, and then 2200μL per dish was added to 293A cells. After 8 hours, the medium was replaced with DMEM, and the cells were collected 2 days after transfection. Cells were collected by removing the medium, washing the cells with 5mL of sterile PBS / dish, then detaching the cells with a cell scraper and transferring them to a 50mL Falcon tube. After centrifugation at 1500rpm for 5min, the supernatant was removed, PBS was added again, washed, and centrifuged at 1500rpm for 5min. The supernatant was removed and stored at -80°C until membrane vesicle preparation.

[0070] (3) Preparation of membrane vesicles The ABCC11 expressing cells prepared in (2) were expanded and ruptured, and then ultracentrifuged at 4°C. The supernatant was discarded, and the water was thoroughly removed. The pellet was then resuspended in an isotonic buffer, and the cells were completely ruptured using a Dounce homogenizer. The cell suspension was layered on 38% sucrose, and ultracentrifuged again.

[0071] After the upper aqueous layer was sucked out after ultracentrifugation, the membrane proteins floating on the intermediate interface were collected, and washed by adding an isotonic buffer solution and ultracentrifuging at 4°C. After washing, the supernatant was removed, and an isotonic buffer solution was added and mixed by pipetting, followed by syringe homogenization to obtain membrane vesicles. The membrane vesicles were frozen and stored at -80°C until use. In addition, membrane vesicles were prepared from control cells using the same procedure and used as control membrane vesicles.

[0072] (4) Evaluation of ABCC11 inhibitory effect As a substrate of ABCC11 (a substance transported by ABCC11), 3 H]estrone sulfate (E1S) or [ 3 H]dehydroepiandrosterone sulfate (DHEAS) (both manufactured by Perkin-Elmer Japan) was used.

[0073] The reaction solution was incubated for 5 minutes under the following four conditions, and the radioactivity (decomposition parameter) derived from the substrate incorporated into the membrane vesicles was measured. (a) In the reaction solution, control membrane vesicles were 5.0 or 7.5 μg / 20 μL, no ATP was contained, and substrate was 100 nM (Mock ATP(-)). (i) In the reaction solution, control membrane vesicles were 5.0 or 7.5 μg / 20 μL, ATP was 5 mM, and substrate was 100 nM (Mock ATP(+)). (c) In the reaction solution, membrane vesicles were 5.0 or 7.5 μg / 20 μL, no ATP was added, and substrate was 100 nM (ABCC11 ATP(-)). (e) In the reaction solution, membrane vesicles were 5.0 or 7.5 μg / 20 μL, ATP was 5 mM, and substrate was 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, the ABCC11-dependent transport activity (= ABCC11 ATP(+) - ABCC11 ATP(-) - ATP-dependent transport activity in the control membrane vesicles) was calculated based on the calculated radioactivity.

[0075] In addition, the soybean extract prepared in (1) was added to the reaction solution to a final concentration of 100 ppm (100 mg / L), and measurements were performed under the same conditions. The inhibition rate of ABCC11 transport activity by the soybean extract was then calculated according to the following formula. Inhibition rate = {1-(ABCC11-dependent transport activity with soybean extract added / ABCC11-dependent transport activity without soybean extract added)} x 100 (%)

[0076] The results are shown in Table 1. [Table 1]

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

[0078] [Test Example 2: Evaluation of ABCC11 inhibitory effect of flavonoids] (1) Preparation of ABCC11-expressing cells (Construction of adenovirus for expressing human ABCC11) The full length amino acid coding sequence of human ABCC11 was inserted 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 an adenovirus for expressing ABCC11. The obtained recombinant plasmid and a control plasmid not containing the ABCC11 gene were each purified and linearized by treating with the restriction enzyme PacI at 37°C for 2 hours. The linearized plasmid was each introduced into human fetal kidney-derived 293A cells, which are packaging cells, and cultured for several weeks to produce ABCC11-expressing adenovirus or control adenovirus. Each adenovirus contained in the cells and culture medium after culture was collected and roughly purified, and each was infected into new 293A cells to amplify the adenovirus. After repeated 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 cultured in a 10 cm dish (Greiner) at 3.0 × 10 6 The cells were seeded at a cell density of 1000 cells / dish and cultured at 37°C under 5% CO2 for 24 hours. The cells were infected with ABCC11 expression vector and control vector (EGFP-expressing adenovirus) at 2.5 MOI (multiplicity of infection) / dish, and harvested 48 hours later. Cells were harvested by removing the medium, washing the cells with 5 mL of sterile PBS / dish, detaching the cells with a cell scraper, and transferring them to a 50 mL Falcon tube. After centrifugation at 1500 rpm for 5 min, the supernatant was removed, PBS was added again, washed, and centrifuged at 1500 rpm for 5 min. The supernatant was removed, and the cells were 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 by the same procedure as in Test Example 1. Control membrane vesicles were also prepared by the same procedure.

[0081] (3) Evaluation of ABCC11 inhibitory effects of flavonoids The compounds shown in Table 2 were evaluated as flavonoids. 3 H] dehydroepiandrosterone sulfate (DHEAS) (Perkin-Elmer Japan) was used. The reaction solution was incubated for 5 minutes under the following four conditions, and the radioactivity (decay parameter) derived from the substrate taken up into the membrane vesicles was measured. (a) In the reaction solution, control membrane vesicles were 10.0 μg / 20 μL, no ATP was added, and substrate was 100 nM (Mock ATP(-)). (i) In the reaction solution, control membrane vesicles were 10.0 μg / 20 μL, ATP was 5 mM, and substrate was 100 nM (Mock ATP(+)). (c) In the reaction solution, membrane vesicles 10.0 μg / 20 μL, ATP-free, substrate 100 nM (ABCC11 ATP(-)). (e) In the reaction mixture, membrane vesicles were 10.0 μg / 20 μL, ATP was 5 mM, and substrate was 100 nM (ABCC11 ATP(+)).

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

[0083] Flavonoids were also added to the reaction solution to a final concentration of 100 ppm (100 mg / L), and measurements were performed under the same conditions. The inhibition rate of ABCC11 transport activity by flavonoids was then calculated according to the following formula. Each flavonoid was measured in triplicate. Inhibition rate = {1-(ABCC11-dependent transport activity with the addition of flavonoids / ABCC11-dependent transport activity without the addition of flavonoids)} x 100 (%)

[0084] The results are shown in Table 2. [Table 2]

[0085] As shown in Table 2, flavonoids were found to have an ABCC11 inhibitory effect (inhibitory effect on the transport activity of ABCC11).

Claims

[Claim 1] An agent that suppresses the secretion of substances that cause body odor, containing flavonoids as active ingredients.

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