Foot odor suppressant

Abstract

To provide a foot odor inhibitor that inhibits foot odors by suppressing the production of isovaleric acid, a substance mainly responsible for foot odors.SOLUTION: A foot odor inhibitor includes at least one selected from the group consisting of biflorin and isobiflorin. as an active ingredient.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a foot odor inhibitor.

Background Art

[0002] Body odor is a general term for odors generated from various parts of the body. The main sites of generation include the head (scalp and hair odor), oral cavity (halitosis), axilla (bromhidrosis axillaris), groin, sole of the foot (foot odor), etc.

[0003] Isovaleric acid (IVA) is known as a main causative substance of foot odor. Isovaleric acid is produced by the metabolism of L-leucine derived from sweat and keratin by skin commensal bacteria, continuously volatilizes to emit an odor, and also adheres to shoes and socks. With the increasing emphasis on cleanliness, the number of people concerned about body odor is increasing, and for foot odor, which is an unpleasant odor, the technology for suppressing it is increasingly desired.

[0004] On the other hand, bifrorin and isobiflorin are trace components contained in various plants, and for bifrorin, it has been reported to have an antitumor effect (Non-Patent Document 1). However, it is not known what effects bifrorin and isobiflorin have on foot odor and isovaleric acid, which is its main causative substance.

Prior Art Documents

Non-Patent Documents

[0005]

Non-Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0006] The present invention relates to providing a foot odor inhibitor that suppresses foot odor by inhibiting the production of isovaleric acid, which is the main cause of foot odor. [Means for solving the problem]

[0007] In view of the above problems, the present inventors conducted research and found that biflorin and isobiflorin have the effect of suppressing the production of isovaleric acid by commensal skin bacteria and inhibiting leucine dehydrogenase, which is involved in the isovaleric acid production pathway, and can be used to suppress foot odor.

[0008] In other words, the present invention relates to the following 1) to 3). 1) A foot odor inhibitor comprising at least one selected from the group consisting of biflorin and isobiflorin as an active ingredient. 2) An isovaleric acid production inhibitor comprising at least one selected from the group consisting of biflorin and isobiflorin as an active ingredient. 3) A leucine dehydrogenase inhibitor comprising at least one selected from the group consisting of biflorin and isobiflorin as an active ingredient. [Effects of the Invention]

[0009] According to the present invention, foot odor can be suppressed by inhibiting the production of isovaleric acid, which is the main cause of foot odor. [Modes for carrying out the invention]

[0010] In this invention, biflorin refers to 5,7-dihydroxy-2-methyl-6-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]-4H-chromen-4-one, which is represented by the following formula.

[0011] [ka]

[0012] Biflorin is commercially available and sold by manufacturers such as Nagara Science Co., Ltd. Alternatively, biflorin may be obtained by extraction and purification from plants containing biflorin, such as Capraria biflora L. and Baeckea frutescens.

[0013] In this invention, isobiflorin refers to 5,7-dihydroxy-2-methyl-8-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]-4H-chromen-4-one, which is represented by the following formula.

[0014] [ka]

[0015] Isobiflorin is commercially available and sold by manufacturers such as Analytical Discovery. Isobiflorin may also be obtained by extraction and purification from plants containing isobiflorin, such as Capraria biflora L. and Baeckea frutescens.

[0016] Biflorin and isobiflorin may be used individually or in combination.

[0017] As shown in the examples described later, biflorin and isobiflorin (hereinafter collectively referred to as "the compounds of the present invention") each have the effect of suppressing the production of isovaleric acid (IVA) by commensal skin bacteria. Furthermore, the compounds of the present invention each have the effect of inhibiting leucine dehydrogenase. Isovaleric acid is the main cause of foot odor and is produced from L-leucine derived from sweat and keratin through the action of leucine dehydrogenase possessed by commensal skin bacteria. Therefore, it is believed that the compounds of the present invention can suppress foot odor by inhibiting the production of isovaleric acid based on the inhibition of leucine dehydrogenase in commensal skin bacteria.

[0018] Therefore, the compounds of the present invention can be used as foot odor suppressants, isovaleric acid production inhibitors, leucine dehydrogenase inhibitors (hereinafter referred to as "foot odor suppressants, etc."), and can also be used for producing such foot odor suppressants, etc. In addition, the compounds of the present invention can be used for suppressing foot odor, suppressing the production of isovaleric acid, and inhibiting leucine dehydrogenase. Here, such use can be in humans or non-human animals, or in specimens derived therefrom, and can be either therapeutic use or non-therapeutic use. Note that "non-therapeutic" is a concept that does not include medical acts, that is, a concept that does not include methods of operating on, treating, or diagnosing humans. More specifically, it is a concept that does not include methods by which a doctor or a person under the doctor's instruction performs surgery, treatment, or diagnosis on a human.

[0019] In the present invention, "foot odor" refers to the odor emitted from the feet, and also refers to the odor of the feet emitted from clothing such as socks and footwear that have come into contact with the feet. Since the main causative substance of foot odor is isovaleric acid, foot odor is preferably the odor of isovaleric acid. "Suppression of foot odor" includes attenuation, disappearance, or suppression of the occurrence of such foot odor, and is preferably suppression of the occurrence of foot odor by suppressing the production of isovaleric acid. "Foot" refers to the part from the ankle joint to the tip, and includes parts such as the instep (dorsum pedis), the sole (plantar surface), the heel, and the toes. Suppression of foot odor is preferably suppression of the odor emitted from the sole of the foot.

[0020] Isovaleric acid, which is the main causative substance of foot odor, is typically produced when L-leucine derived from sweat or the stratum corneum is oxidized to 4-methyl-2-oxopentanoic acid by leucine dehydrogenase possessed by skin commensal bacteria, and then undergoes oxidative decarboxylation. Here, "leucine dehydrogenase" refers to water and NAD +It is an oxidoreductase (EC 1.4.1.9) that catalyzes the oxidation of L-leucine to 4-methyl-2-oxopentanoic acid in the presence of [unspecified substance]. While not limited to these, common skin flora include bacteria of the genus Corynebacterium such as Corynebacterium striatum and Corynebacterium xerosis; bacteria of the genus Bacillus such as Bacillus subtilis; bacteria of the genus Staphylococcus such as Staphylococcus aureus; and bacteria of the genus Propionibacterium such as Propionibacterium acnes. "Leucine dehydrogenase inhibition" includes inhibiting the activity of leucine dehydrogenase, reducing the amount of the enzyme's protein, and reducing the expression of the gene encoding the enzyme, and preferably inhibiting the activity of leucine dehydrogenase. Furthermore, the amount of isovaleric acid produced can be measured using known measurement methods such as LC / MS. In addition, the inhibition rate of leucine dehydrogenase can be calculated using known measurement methods, for example, by capturing the amount of NADH produced as a by-product during the reaction by the enzyme as absorbance and using this as an indicator.

[0021] The foot odor inhibitors of the present invention may themselves be pharmaceuticals, quasi-drugs, or cosmetics for human or animal use that exert the effects of foot odor suppression, isovaleric acid production suppression, and leucine dehydrogenase inhibition, or they may be materials or formulations used when incorporated into such pharmaceuticals, quasi-drugs, or cosmetics.

[0022] When the foot odor inhibitor of the present invention is used as a pharmaceutical product (including quasi-drugs), the pharmaceutical product can be administered in any dosage form, but parenteral administration is preferred, and parenteral administration by topical preparation is more preferred. For example, the pharmaceutical product or quasi-drug may be in the form of a topical skin preparation such as an ointment, cream, emulsion, lotion, gel, aerosol, patch, tape, or spray. Pharmaceutical formulations of various dosage forms can be prepared by appropriately combining the compound of the present invention with other pharmaceutically acceptable excipients, binders, bulking agents, disintegrants, diluents, thickeners, emulsifiers, lubricants, dispersants, coating agents, surfactants, coating agents, osmotic pressure regulators, buffers, pH adjusters, preservatives, stabilizers, antioxidants, colorants, flavoring agents, deodorizers, fragrances, etc.

[0023] When the foot odor suppressant of the present invention is used as a cosmetic, the form of the cosmetic can be any form that can be used as a cosmetic, such as a cream, emulsion, lotion, suspension, foam, gel, powder, pack, sheet, patch, stick, cake, etc. Such cosmetics can be prepared by conventional methods by appropriately combining the compound of the present invention with a carrier acceptable as a cosmetic composition (for example, a diluent, dispersant, buffer, pH adjuster, emulsifier, surfactant, preservative, stabilizer, antioxidant, colorant, UV absorber, humectant, thickener, bactericide, fragrance, etc.).

[0024] The content of the compound of the present invention in the pharmaceutical or cosmetic product is preferably 0.00001% by mass or more, more preferably 0.0001% by mass or more, even more preferably 0.001% by mass or more, and preferably 5% by mass or less, more preferably 2% by mass or less, and even more preferably 1% by mass or less. Furthermore, the content is preferably 0.00001 to 5% by mass, more preferably 0.0001 to 2% by mass, even more preferably 0.0001 to 1% by mass, and even more preferably 0.001 to 1% by mass.

[0025] The dosage of the foot odor inhibitor, etc., of the present invention may be an amount that can achieve the effects of the present invention. The dosage may vary depending on the species, weight, sex, age, condition, or other factors of the subject. The dosage, route, interval, and amount and interval of administration may be appropriately determined by those skilled in the art. For example, the dosage, in terms of the compound of the present invention, is preferably 0.01 mg or more, more preferably 0.1 mg or more, even more preferably 1 mg or more, and preferably 1000 mg or less, more preferably 500 mg or less, and even more preferably 100 mg or less per day for one adult (weighing 60 kg). Also, it is preferably 0.01 to 1000 mg per day, more preferably 0.1 to 500 mg, and even more preferably 1 to 100 mg. In the case of administration by applying topical preparations such as cosmetics, 100 cm 2 The single dose per administration is preferably 0.01 mg or more, more preferably 0.05 mg or more, even more preferably 0.1 mg or more, and preferably 1000 mg or less, more preferably 500 mg or less, and even more preferably 100 mg or less, in terms of the compound of the present invention. Also preferably 0.01 to 1000 mg, more preferably 0.05 to 500 mg, and even more preferably 0.1 to 100 mg.

[0026] The foot odor inhibitor of the present invention can be administered once to several times a day, or at any duration and interval. The duration of administration can be determined as appropriate; for example, it is preferably 1 day or more, more preferably 7 days or more, and even more preferably 30 days or more.

[0027] The target of administration includes animals, preferably humans, and is not particularly limited if it is necessary, but more preferably humans who wish to suppress foot odor, humans who are at risk of developing foot odor, or humans who wish to prevent the development of foot odor. The foot odor is preferably one mainly caused by isovaleric acid. It is generally preferable to apply the present invention directly to the area where the effect is expected to manifest, such as the top of the foot (dorsal surface), the sole of the foot (sole), the heel, and the toes, with the sole of the foot being preferred. [Examples]

[0028] The present invention will be described in more detail below based on examples, but the present invention is not limited thereto.

[0029] Example 1: Inhibitory effect on isovaleric acid (IVA) production (1) Compound Biflorin (manufactured by Nagara Science Co., Ltd.) and isobiflorin (manufactured by Analyticon Discovery Co., Ltd.) were used.

[0030] (2) Evaluation of IVA production by bacteria Corynebacterium striatum (NBRC15291), cultured on SCD agar at 37°C for 24 hours, was suspended in 2 mL of physiological saline using 10 loops of platinum. 100 μL of this suspension was inoculated into 2 mL of 5 / 5 medium (final concentrations: meat extract: 0.05%, polypeptone S: 0.5%, leucine: 0.2%, sodium chloride: 0.75%), and 20 μL of a test sample (28 μM biflorin or 28 μM isobiflorin) or solvent control (solvent component of the test sample) was added. This mixture was then cultured in a closed system with shaking for 24 hours.

[0031] (3) IVA determination by LC / MS 40 μL of the above permeation culture solution was filtered through a 0.20 μm disc membrane filter to obtain a test solution. 20 μL of deuterium-labeled isovaleric acid (IVA-d7, 100 μM) was added as an internal standard, followed by 20 μL of 3-nitrophenyl hydrazine (3-NPH) solution (200 mM) and 20 μL of EDC solution (containing 6% pyridine, 120 mM). The mixture was reacted at 40°C for 30 minutes. After the reaction, 2 mL of 10% acetonitrile was added, and the solution was further diluted 10-fold with 10% acetonitrile to obtain the measurement sample. The measurement sample was subjected to LC / MS under the following conditions to quantify the amount of IVA produced. LC / MS conditions HPLC system: SHIMADZU Nexera Column: CAPCELL CORE (2.7 μm, 2.1 × 50 mm) Mobile phase: A) 0.1% HCOOH aq B)CH3CN Flow rate: 0.5mL / min Injection volume: 10μL

[0032] [Table 1]

[0033] (4) Evaluation of IVA production rate The IVA production rate was calculated using the following formula (1). As shown in Table 2, biflorin and isobiflorin suppressed IVA production by Corynebacterium striatum.

[0034]

number

[0035] [Table 2]

[0036] Example 2: Leucine dehydrogenase inhibitory effect 10 μL of leucine dehydrogenase (Fujifilm Wako Pure Chemical Industries) prepared to 12 U / mL in 250 mM glycine buffer (pH 9.5), 100 μL of 250 mM glycine buffer (pH 10.5), 10 μL of 400 mM leucine, and 60 mM NAD. + 10 μL of water and 66 μL of distilled water were mixed, and 4 μL of the test sample (biflolin with final concentrations of 250 and 500 μM, or isobiflolin with final concentrations of 250 and 500 μM), the comparative test sample (citral with a final concentration of 700 μM (manufactured by Tokyo Chemical Industry Co., Ltd.)), or the solvent control (solvent component of the test sample) was added. The mixture was incubated at 30°C for 5 minutes, and the absorbance was measured at 340 nm. The leucine dehydrogenase inhibition rate was calculated using the following formula (2). As shown in Table 3, biflorin and isobiflorin inhibited the activity of leucine dehydrogenase. Their inhibitory effect was significantly stronger than that of citral, which is known to inhibit leucine dehydrogenase.

[0037]

number

[0038] [Table 3]

Claims

1. An isovaleric acid production inhibitor comprising at least one active ingredient selected from the group consisting of biflorin and isobiflorin.

2. A leucine dehydrogenase inhibitor comprising at least one selected from the group consisting of biflorin and isobiflorin as an active ingredient.

3. The agent according to claim 1 or 2, used for suppressing foot odor.

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