JP7728042B2 - Olfactory receptor-mediated sweating control - Google Patents

Description

The present invention relates to a sweating regulator comprising an agonist or antagonist for at least one receptor selected from the group consisting of olfactory receptors OR6C74, OR51A7, and OR4A15, and a method for screening candidate substances for sweating regulators.

Sweating is an important human physiological function for maintaining health. Decreased sweating (anhidrosis) leads to a rise in body temperature, heatstroke, and dry skin. Excessive sweating (hyperhidrosis) can lead to hypothermia, making it difficult to engage in social activities, for example. Methods for controlling sweating include blocking sweat ducts with aluminum chloride in the case of hyperhidrosis, or using drugs (anticholinergics) that suppress the action of acetylcholine, which induces sweating. However, aluminum chloride is likely to cause irritant dermatitis, and anticholinergics are likely to cause side effects such as dry eyes, dry mouth, headaches, and tachycardia, so they cannot be said to have a wide range of application (Non-Patent Documents 1 and 2). Furthermore, there is currently no established method for inducing sweating in anhidrosis. Given this situation, the establishment of a more harmless and effective method for controlling sweating is desired.

S. Gregoriou et al., Clin Cosmet Investig Dermatol. 2019; 12: 733-744 I. Hoorens et al., J Eur Acad Dermatol Venereol. 2012; 26: 1-8

An object of the present invention is to provide a sweating regulator comprising an agonist or antagonist for at least one receptor selected from the group consisting of olfactory receptors OR6C74, OR51A7, and OR4A15, and a method for screening candidate substances for sweating regulators.

The present inventors first hypothesized that there may be differences in gene expression between the sweat glands of anhidrotic and sweating areas of patients with anhidrotic syndrome, and that these differences may be responsible for anhidrosis. Therefore, the present inventors comprehensively analyzed the genes expressed in sweat glands by RNA sequencing using sweat gland tissues from anhidrotic and sweating areas of patients with anhidrotic syndrome. Surprisingly, they found that olfactory receptors are expressed in sweat glands. Among these olfactory receptors, three types (OR6C74, OR51A7, and OR4A15) showed significantly different expression between the sweat glands of anhidrotic and sweating areas of patients with anhidrotic syndrome. Further investigation was conducted on these three olfactory receptors (OR6C74, OR51A7, and OR4A15) that showed significant differences (p<0.01) in their expression between the sweat glands of anhidrotic and sweating areas of patients with anhidrotic syndrome. As a result, we found that β-ionone (fragrance), an agonist for OR51E2, a receptor related to OR51A7, significantly increased the sweat rate (mg/min) in a quantitative axon reflex sweating test, while α-ionone (fragrance), an antagonist for the same receptor, decreased the sweat rate, leading to the completion of the present invention.

That is, the present invention relates to the following.
[1] A sweat regulating agent comprising an agonist or antagonist for at least one receptor selected from the group consisting of olfactory receptors OR6C74, OR51A7, and OR4A15.
[2] The sweat regulating agent according to [1], which contains an agonist for at least one receptor selected from the group consisting of olfactory receptors OR6C74, OR51A7, and OR4A15.
[3] The sweat regulating agent according to [1], wherein the sweat regulating agent is a sweat promoter.
[4] The sweat regulating agent according to any one of [1] to [3], wherein the agonist is β-ionone.
[5] The sweat regulating agent according to [1], which contains an antagonist for at least one receptor selected from the group consisting of olfactory receptors OR6C74, OR51A7, and OR4A15.
[6] The sweat regulating agent according to [5], wherein the sweat regulating agent is an antiperspirant.
[7] The sweat regulating agent according to any one of [1], [5] and [6], wherein the antagonist is α-ionone.
[8] A method for screening a sweat regulating agent, comprising:
(1) contacting a test substance with at least one receptor protein selected from the group consisting of olfactory receptors OR6C74, OR51A7, and OR4A15;
(2) measuring the binding affinity between the test substance and the receptor protein; and (3) selecting the test substance as a candidate substance for a sweat regulating agent using the measured binding affinity as an index.

According to the present invention, there is provided a sweating regulating agent comprising an agonist or antagonist for at least one receptor selected from the group consisting of olfactory receptors OR6C74, OR51A7, and OR4A15. Use of the agent of the present invention enables effective sweating control that is harmless to the human body.
Furthermore, the present invention provides a screening method for candidate substances for sweating regulators using olfactory receptor proteins (hereinafter sometimes abbreviated as "olfactory receptors"), such as OR6C74 protein (hereinafter sometimes abbreviated as "OR6C74"), OR51A7 protein (hereinafter sometimes abbreviated as "OR51A7"), or OR4A15 protein (hereinafter sometimes abbreviated as "OR4A15"). By using the screening method of the present invention, it is possible to obtain substances that are harmless to the human body and can effectively control sweating.

Figure 1 shows the results of transcriptome analysis in sweating and non-sweating areas. FIG. 2 shows the effects of β-ionone on the olfactory receptors OR6C74, OR51A7, and OR4A15. FIG. 3 shows the effects of a compound other than β-ionone (α-ionone) on the olfactory receptors OR6C74, OR51A7, and OR4A15.

1. Sweat Regulator of the Present Invention The sweat regulator of the present invention comprises an agonist or antagonist for at least one receptor selected from the group consisting of olfactory receptors OR6C74, OR51A7, and OR4A15. As used herein, "olfactory receptor" refers to a receptor that belongs to the G protein-coupled receptor (hereinafter sometimes abbreviated as "GPCR") family, and more specifically, to a class A rhodopsin-like receptor.

As used herein, "OR6C74" refers to an olfactory receptor protein (SEQ ID NO: 2) classified as Olfactory Receptor Family 6 Subfamily C Member 74, and the nucleic acid encoding this protein is also referred to as the "OR6C74 gene" (SEQ ID NO: 1).
As used herein, "OR51A7" refers to an olfactory receptor protein (SEQ ID NO: 4) classified as Olfactory Receptor Family 51 Subfamily A Member 7, and the nucleic acid encoding this protein is also referred to as the "OR51A7 gene" (SEQ ID NO: 3).
As used herein, "OR4A15" refers to Olfactory Receptor Family 4 Subfamily A Member
It is an olfactory receptor protein (SEQ ID NO: 5) classified as er 15, and the nucleic acid encoding this protein is also referred to as the "OR4A15 gene" (SEQ ID NO: 6).

In the present invention, the term "agonist" refers to a substance that binds to a specific receptor and induces a response within a cell, and positive allosteric modulators (PAMs) are also included in the term agonists. An allosteric modulator refers to a molecule that binds to an allosteric site and exerts its action by enhancing or inhibiting the binding or signal transduction of an orthosteric ligand. Allosteric modulators are classified into PAMs according to their effect on the activity of the orthosteric ligand, which can be enhanced, attenuated, or left unchanged.
They can be classified into NAM (Negative Allosteric Modulator), NAM (Negative Allosteric Modulator), and SAM (Silent (or neutral) Allosteric Modulator). Suitable agonists contained in the agent of the present invention include, for example, β-ionone, pelargonic acid, and capric acid.
The agent of the present invention functions as a sweat promoter when it contains an agonist for specific receptors (R6C74, OR51A7, and OR4A15). The sweat promoter can be used, for example, to prevent or treat congenital/genetic or acquired anhidrosis, preferably idiopathic anhidrosis, more preferably acquired idiopathic generalized anhidrosis. Furthermore, since the sweat promoter can lower body temperature through sweating, it can also be used, for example, to treat heatstroke. Furthermore, the sweat promoter can also be used to protect dry skin caused by aging.

As used herein, the term "antagonist" refers to a substance that reduces, inhibits, or prevents the action of another molecule or the activity of a receptor site. Antagonists include, but are not limited to, competitive antagonists, noncompetitive antagonists, uncompetitive antagonists, ion channel inhibitors, and NAMs. Competitive antagonists reversibly bind to the receptor at the same binding site (active site) as the endogenous ligand or agonist, but do not activate the receptor. Noncompetitive antagonists (also known as allosteric antagonists) bind to a site different from the agonist's binding site and act on the receptor via an alternative binding site. Noncompetitive antagonists do not compete with agonists for binding. A bound antagonist may reduce the affinity of an agonist for the receptor or prevent the conformational changes in the receptor required for receptor activation after agonist binding. Uncompetitive antagonists differ from non-competitive antagonists in that they require receptor activation by an agonist before binding to the allosteric binding site. Antagonists also include antibodies, aptamers, dominant-negative mutants, and the like that inhibit the function of receptors or calcium channels. Suitable antagonists included in the agent of the present invention include, for example, α-
Ionone, 2-ethylhexanoic acid.
When the agent of the present invention contains an antagonist for specific receptors (R6C74, OR51A7, and OR4A15), it functions as an antiperspirant, which can be used to prevent or treat, for example, hyperhidrosis and body odor.

The agent of the present invention can be incorporated into cosmetics or pharmaceuticals (including quasi-drugs), or the agent of the present invention may itself be used as a cosmetic or pharmaceutical (including quasi-drugs).

When the agent of the present invention is incorporated into cosmetics, or when the composition of the present invention itself is used as a cosmetic, the types of cosmetics include, for example, skin cosmetics such as facial cleansers, lotions, emulsions, creams, gels, serums, packs, and masks; makeup cosmetics such as face powder, foundation, lipstick, blush, eyeliner, mascara, eye shadow, and eyebrow pencil; and hair cosmetics such as shampoos, rinses, hair conditioners, hair styling agents, hair treatments, and hair mists.

When the agent of the present invention is incorporated into a cosmetic preparation, or when the agent of the present invention itself is used as a cosmetic preparation, the cosmetic preparation may contain ingredients that may be added to conventional cosmetic preparations to the extent that the effects of the present invention are not impaired. Specific examples of such ingredients include oils, chelating agents, surfactants, powders, sugar alcohols and their alkylene oxide adducts, lower alcohols, animal and plant extracts, nucleic acids, enzymes, anti-inflammatory agents, disinfectants, preservatives, antioxidants, UV absorbers, antiperspirants, pigments, colorants, oxidation dyes, organic and inorganic powders, pH adjusters, pearlizing agents, humectants, etc.

Examples of oils include higher alcohols such as cetyl alcohol, isostearyl alcohol, lauryl alcohol, hexadecyl alcohol, and octyldodecanol; fatty acids such as isostearic acid, undecylenic acid, and oleic acid; esters such as myristyl myristate, hexyl laurate, decyl oleate, isopropyl myristate, hexyldecyl dimethyloctanoate, glycerin monostearate, diethyl phthalate, ethylene glycol monostearate, octyl oxystearate, alkyl benzoate, di(phytosteryl/octyldodecyl) lauroyl glutamate, and cetyl octanoate;
Examples include hydrocarbons such as liquid paraffin, polyisobutene, petrolatum, and squalane; waxes such as lanolin, reduced lanolin, and carnauba wax; oils and fats such as mink oil, cocoa oil, coconut oil, palm kernel oil, camellia oil, sesame oil, castor oil, and olive oil; ethylene-α-olefin co-oligomers; and silicone oils.

Specific examples of silicone oils include ether-modified silicones such as methylpolysiloxane, highly polymerized methylpolysiloxane, polyoxyethylene-methylpolysiloxane copolymer, polyoxypropylene-methylpolysiloxane copolymer, and poly(oxyethylene, oxypropylene)-methylpolysiloxane copolymer; stearoxytrimethylsilane, methylhydrogenpolysiloxane, decamethylcyclopentasiloxane, octamethylcyclotetrasiloxane, tetrahydrotetramethylcyclotetrasiloxane, methylcyclopolysiloxane, and dodecamethylcyclohexylsiloxane. Examples of silicone oils include silicone oils selected from the group consisting of cyclic silicones such as cyclohexanesiloxane; amino-modified silicones such as methylphenylpolysiloxane, trimethylsiloxysilicate, and aminoethylaminopropylsiloxane-dimethylsiloxane copolymer; alkoxy-modified polysiloxanes such as silanol-modified polysiloxane and stearoxymethylpolysiloxane, fatty acid-modified polysiloxane, fluorine-modified polysiloxane, epoxy-modified polysiloxane, alkoxy-modified polysiloxane perfluoropolyether, polyvinyl acetate dimethylpolysiloxane, and mixtures thereof.

The chelating agent is not particularly limited, but preferred are triethylenetetramine, 2-thenoyltrifluoroacetone, thioglycolic acid, tartaric acid, succinic acid, 8-quinolinol, pyridine-2,6-dicarboxylic acid, pyridine, 1,10-phenanthroline, lactic acid, 8-hydroxyquinoline-5-sulfonic acid, glycine, 2,2'-pyridylethylenediamine, aurintricarboxylic acid, xylenol orange, 5-sulfosalicylic acid, salicylic acid, pyrocatechol-3,5-disulfonate, 4,5-dihydroxybenzene-1,3-disulfonic acid, 1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid, citric acid, oxalate, nitrilotriacetic acid, ethylenediamine-
Included are chelating agents selected from the group consisting of N,N,N',N-tetraacetic acid, acetylacetone and salts thereof, and mixtures thereof.

Examples of surfactants include anionic surfactants such as N-long-chain acyl amino acid salts, such as N-long-chain acyl acidic amino acid salts and N-long-chain acyl neutral amino acid salts, N-long-chain fatty acid acyl-N-methyl taurine salts, alkyl sulfates and their alkylene oxide adducts, fatty acid amide ether sulfates, metal salts and weak base salts of fatty acids, sulfosuccinic acid surfactants, alkyl phosphates and their alkylene oxide adducts, and alkyl ether carboxylic acids; ether-type surfactants, such as glycerin ethers and their alkylene oxide adducts and polyoxyethylene polyoxypropylene alkyl ethers; ether ester-type surfactants, such as alkylene oxide adducts of glycerin esters, alkylene oxide adducts of sorbitan esters, and polyoxyalkylene hydrogenated castor oil; and polyoxyalkylene alkyl esters. Examples of such surfactants include ester surfactants such as olefin fatty acid esters, glycerin esters, fatty acid polyglycerin esters, sorbitan esters, and sucrose fatty acid esters; nitrogen-containing nonionic surfactants such as alkyl glucosides, hydrogenated castor oil pyroglutamic acid diesters and their ethylene oxide adducts, and fatty acid alkanolamides; cationic surfactants such as aliphatic amine salts such as alkyl ammonium chloride and dialkyl ammonium chloride; quaternary ammonium salts such as alkyl triethyl ammonium chloride and dialkyl dimethyl ammonium chloride; aromatic quaternary ammonium salts such as benzalkonium salts; and fatty acid acyl arginine esters; as well as amphoteric surfactants such as betaine surfactants such as carboxybetaine, aminocarboxylic acid surfactants, and imidazoline surfactants.

Examples of powders include resin powders such as nylon beads and silicone beads, nylon powder, metal fatty acid soap, yellow iron oxide, red iron oxide, black iron oxide, chromium oxide, cobalt oxide, carbon black, ultramarine, Prussian blue, zinc oxide, titanium oxide, zirconium oxide, silicon oxide, aluminum oxide, cerium oxide, titanium mica, boron nitride, barium sulfate, calcium carbonate, magnesium carbonate, aluminum silicate, magnesium silicate, silicon carbide, pigments, lake, sericite, mica, talc, kaolin, plate-shaped barium sulfate, butterfly-shaped barium sulfate, fine titanium oxide particles, fine zinc oxide particles, fine iron oxide particles, acylamino acids such as acyl lysine, acyl glutamic acid, acyl arginine, and acyl glycine, and may be surface-treated with silicone, fluorine compound, silane coupling agent, silane-treated organic titanate, acylated lysine, fatty acid, metal soap, oil, or amino acid.

Examples of sugar alcohols and their alkylene oxide adducts include mannitol.

Examples of lower alcohols include ethanol and propanol.

When the agent of the present invention is incorporated into a medicine (including quasi-drugs), or when the agent of the present invention itself is used as a medicine (including quasi-drugs), examples of the dosage form of the medicine include topical preparations such as ointments (aqueous ointments, oily ointments, etc.), creams, liquids, emulsions, gels, lotions, liniments, and pastes; adhesive preparations such as poultices, plasters, tapes, and patches; spray preparations such as aerosols and sprays; and suppositories.

When the agent of the present invention is incorporated into a medicine (including quasi-drugs), or when the agent of the present invention itself is used as a medicine (including quasi-drugs), the medicine may contain pharmacologically acceptable carriers, excipients, diluents, soothing agents, preservatives, antioxidants, etc., to the extent that the effects of the present invention are not impaired.

The agent of the present invention is a skin composition, and is preferably incorporated into a skin cosmetic or skin pharmaceutical (including quasi-drugs for skin), or the agent of the present invention itself is preferably made into a skin cosmetic or skin pharmaceutical (including quasi-drugs for skin). Here, "skin" is a concept that encompasses not only the epidermis of the body (e.g., face, head, neck, chest, abdomen, waist, back, buttocks, arms, legs, hands, etc.) but also mucous membranes, and "for skin" means to be applied to the skin.

Examples of subjects to which the agent of the present invention can be applied include, but are not limited to, mammals (e.g., humans, mice, rats, hamsters, rabbits, cats, dogs, cows, sheep, monkeys, etc.).

The dosage of the agent of the present invention and the number of times it is administered to a subject can be adjusted appropriately depending on the form of the agent, the subject to which it is administered, the body weight of the subject, and the like.

In addition to the above, the agent of the present invention can also be incorporated into cleaning agents, or the agent of the present invention can itself be used as a cleaning agent.

When the detergent is a liquid, the pH is typically 6 to 10, preferably 7 to 10, and more preferably 7.5 to 9.5. This range allows for the provision of a detergent composition with excellent usability. When the detergent is not a liquid, the pH is defined as the pH of a 10% aqueous solution (25°C), and conforms to the above pH range.

Various commonly used additives may be added to the above-mentioned cleaning agent within the range that does not impair the effects of the present invention. Examples of such ingredients include higher alcohols such as cetyl alcohol, stearyl alcohol, behenyl alcohol, isostearyl alcohol, octyldodecanol, oleyl alcohol, and myristyl alcohol; higher fatty acids such as hydrogenated beef tallow fatty acid, coconut oil fatty acid, and palm oil fatty acid, and salts thereof (excluding fatty acids having 6 to 24 carbon atoms or salts thereof); moisturizers such as trimethylglycine; surfactants such as anionic surfactants, cationic surfactants, amphoteric surfactants, and nonionic surfactants; vegetable oils, animal fats and oils, natural fat derivatives, mineral fats and oils, synthetic fats and oils such as lower and higher fatty acid esters; silicone compounds, polymeric substances, animal and plant extracts, amino acids, nucleic acids, vitamins, enzymes, anti-inflammatory agents, bactericides, preservatives, antioxidants, UV absorbers, chelating agents, antiperspirants, oxidative dyes, pH adjusters, and pearlizing agents, as well as raw materials described in various official standards such as the Standards for Cosmetic Raw Materials, Standards for Ingredients by Cosmetic Type, Standards for Quasi-drug Raw Materials, Japanese Pharmacopoeia, Standards for Ingredients of Non-Pharmacopoeia Drugs in Japan, and the Official Standards for Food Additives.

Depending on the purpose of use, the above detergents can be used in shampoos, facial cleansers, body shampoos, hand soaps, shaving products, kitchen cleaners, and laundry detergents.

2. Screening Method for Perspiration Regulators of the Present Invention The screening method for perspiration regulators of the present invention comprises the following steps:
(1) contacting a test substance with at least one receptor protein selected from the group consisting of olfactory receptors OR6C74, OR51A7, and OR4A15;
(2) measuring the binding affinity between the test substance and the receptor protein; and (3) selecting the test substance as a candidate substance for a sweat regulating agent using the measured binding affinity as an index.

The binding affinity of an olfactory receptor protein to a test substance (i.e., a candidate substance for a sweat regulator) can be measured, for example, by directly measuring the binding between the test substance and the olfactory receptor protein, or by measuring the activation of the olfactory receptor protein by the test substance and using this measured value as an index of binding. Furthermore, there are no particular limitations on the method for measuring the binding affinity of an olfactory receptor protein to a test substance, as long as it is possible to measure the above-mentioned binding or activation, but examples include the following methods.

The binding between a test substance and an olfactory receptor protein can be measured by known methods for measuring binding between substances, such as the binding between the protein and a ligand, including, for example, isothermal titration calorimetry (ITC), surface plasmon resonance (SPR), nuclear magnetic resonance (NMR), and fluorescence correlation spectroscopy (FCS).

The activation of olfactory receptor proteins by a test substance can be measured, for example, by known methods for measuring the activity of receptors such as olfactory receptors. Specific examples include intracellular calcium level measurement and intracellular cAMP level measurement. The activation of olfactory receptor proteins by a test substance can be measured, for example, using the intracellular calcium level or intracellular cAMP level as an indicator. For example, in HEK293T cells, it is known that when olfactory receptors are activated by aroma components, they couple with intracellular G proteins (such as Golf) to activate adenylate cyclase and increase the intracellular cAMP level (Kajiya K. et al., Journal of Neuroscience, 2001, 21:6018-6025).

Methods for measuring the intracellular cAMP level include, for example, ELISA and reporter assay. Examples of reporter assays include luciferase assay. Reporter assays allow the measurement of intracellular cAMP levels using a reporter gene (e.g., luciferase gene) whose expression is configured to depend on the cAMP level. Methods for measuring intracellular calcium levels include, for example, calcium imaging and patch clamping. Calcium imaging allows the measurement of intracellular calcium levels using calcium indicators. Examples of calcium indicators include calcium-sensitive fluorescent dyes and calcium-sensitive fluorescent proteins. Examples of calcium-sensitive fluorescent dyes include Fura 2 and Fluo 4. Examples of calcium-sensitive fluorescent proteins include Cameleon, TN-XL, GCaMP, and G-GECO.

The measured value of the binding activity of olfactory receptor proteins to the test substance (i.e., a candidate substance for a sweat regulating agent) obtained by the method described above can be used to select a candidate substance by setting an appropriate standard value in accordance with the desired level of sweat regulating ability and comparing the measured value with the standard value.

The present invention will be explained in detail below using examples, but the present invention is not limited to these examples in any way.

Example 1 Transcriptome Analysis Using paraffin block samples of skin obtained from the sweating areas (skin with remaining sweating function) and anhidrosis areas (skin with impaired sweating function) of three anhidrosis patients, sweat glands were collected by laser microdissection. Total RNA was extracted from the sweat glands using the Rneasy (registered trademark) FFPE kit (QIAGEN) according to the manufacturer's recommended protocol, and RNA sequencing was performed.
Library preparation was performed using the TruSeq® Strand mRNA Sample Preparation Kit (Illumina) according to the manufacturer's recommended protocol. Sequencing was performed on a HiSeq® 2500 platform (Illumina). Casava® 1.8.2 software (Illumina) was used for base calling. Reads were mapped to the human genome reference using TopHat® v2.0.13 and Bowtie (John Hopkins University).
A combination of SAMtools® ver. 2.2.3 and SAMtools® ver. 0.1.19 was used. Mapped fragments were calculated using Cufflinks® ver. 2.2.1. Sweat glands in the sweating and non-sweating areas of the same individual were compared, and genes whose RNA expression changed by 2-fold or more with a p-value of <0.01 and showed the same change in all three individuals were extracted.
As a result, we discovered the presence of olfactory receptors (OR6C74, OR51A7, and OR4A15) that are expressed in sweating areas and whose expression is reduced in anhidrotic areas (Figure 1).

Example 2 Olfactory Receptor Evaluation Test 1
Olfactory receptors (OR6C74, OR51A7, and OR4A15) whose expression is decreased in anhidrotic areas found in Example 1
A test to evaluate the sweating function of the olfactory receptor using β-ionone, which selectively stimulates acetylcholine (Ach), was conducted (acetylcholine (Ach)-stimulated sweating was measured using a real-time sweat meter).
Axon reflex sweating test (QSART) was performed.
The experimental method involved applying a base and β-ionone-containing formulation to one arm, and applying only the base to the other arm, and measuring the amount of sweating per 5 minutes on both the left and right sides simultaneously. As can be seen from the results, the arm to which the base and β-ionone-containing formulation was applied had a sweating rate of 1.829 mg/5 min, while the arm to which the base and β-ionone-containing formulation was applied had a sweating rate of 1.829 mg/5 min.
With the base alone, the sweating rate was 0.568 mg/5 min (Figure 2), a 3.22-fold increase. These results confirmed that β-ionone can be used as an agonist for olfactory receptors (OR6C74, OR51A7, and OR4A15) and can promote sweating.

Example 3 Olfactory Receptor Evaluation Test 2
A QSART test was conducted to evaluate the effects of compounds other than β-ionone on olfactory receptors (OR6C74, OR51A7, and OR4A15). The test was conducted in the same manner as in Example 2, except that α-ionone was used instead of β-ionone. As can be seen from the results, the sweat rate on the arm where the formulation containing base and α-ionone was applied was 1.182 mg/5 min, compared to 2.119 mg/5 min with base alone (Figure 3), a reduction of approximately 0.56-fold. These results demonstrate that α-ionone can be used as an antagonist for olfactory receptors (OR6C74, OR51A7, and OR4A15) and can suppress sweating.

The sweat regulating agent of the present invention, which comprises an agonist or antagonist for at least one receptor selected from the group consisting of olfactory receptors OR6C74, OR51A7, and OR4A15, is harmless to the human body and can be used to effectively control sweating.

Claims (7)

1. A method for screening a sweat regulating agent, comprising:
(1) contacting a test substance with at least one receptor protein selected from the group consisting of olfactory receptors OR51E2, OR51A7, OR6C74, and OR4A15;
(2) measuring the binding affinity between the test substance and the receptor protein; and (3) selecting the test substance as a candidate substance for a sweating regulator using the measured binding affinity as an index. Step (1) is a step of contacting a test substance with at least one receptor protein selected from the group consisting of olfactory receptors OR51E2 and OR51A7;
The screening method according to claim 1. Step (1) is a step of contacting a test substance with a receptor protein of the olfactory receptor OR51E2;
The screening method according to claim 1. The screening method according to any one of claims 1 to 3, wherein in step (1), the test substance is a fragrance. In step (3), a test substance whose measured binding ability indicates agonistic activity against the receptor is selected as a candidate substance for a sweat promoter.
The screening method according to any one of claims 1 to 4. In step (3), a test substance whose measured binding ability indicates antagonist activity against the receptor is selected as a candidate substance for an antiperspirant.
The screening method according to any one of claims 1 to 4. A skin perspiration promoter containing beta-ionone as a perspiration-promoting ingredient.