COMPOSITION FOR ACTIVATING HAIR FOLLICLE STEM CELLS, COMPOSITION FOR INHIBITING EXPRESSION OF wnt3 GENE IN HAIR FOLLICLE STEM CELLS, AND COMPOSITION FOR INHIBITING EXPRESSION OF bmp4 GENE IN HAIR FOLLICLE STEM CELLS

Abstract

The purpose of the present invention is to provide a composition for activating hair follicle stem cells, the composition being naturally derived, being considered to have safety, and containing an ingredient capable of activating hair follicle stem cells as an active ingredient. The purpose is achieved by a composition for activating hair follicle stem cells, the composition comprising: at least one first active ingredient selected from the group consisting of 10-hydroxy-2-decenoic acid, a derivative thereof, and salts thereof; and at least one second active ingredient selected from the group consisting of 2-decenedioic acid, a derivative thereof, and salts thereof.

Description

Composition for activating hair follicle stem cells, composition for inhibiting the expression of the wnt3 gene in hair follicle stem cells, and composition for inhibiting the expression of the bmp4 gene in hair follicle stem cells

[0001] The present invention relates to a composition for activating hair follicle stem cells, a composition for inhibiting the expression of the wnt3 gene in hair follicle stem cells, and a composition for inhibiting the expression of the bmp4 gene in hair follicle stem cells.

[0002] The Wnt signaling pathway and the Bmp (Bone Morphogenetic Protein) signaling pathway are both composed of multiple factors and transmit signals into cells via cell surface receptors. Both of these signaling pathways play important roles in early development, regulating intercellular signals related to cell differentiation and tissue arrangement, and functioning to appropriately control intercellular interactions.

[0003] Wnt3 (Wnt Family Member 3) in the Wnt signaling pathway and Bone Morphogenetic Protein 4 (Bmp4) in the Bmp signaling pathway are known to be involved in maintaining the stemness of hair follicle stem cells (see, for example, Non-Patent Documents 1 and 2).

[0004] Hair follicle stem cells remain quiescent while maintaining their stemness until the telogen phase. During the transition from telogen to anagen, hair follicle stem cells proliferate and differentiate. When the expression levels of Wnt3 protein and Bmp4 protein decrease, hair follicle stem cells are released from their quiescent state and transition from telogen to anagen. That is, the decrease in Wnt3 protein and Bmp4 protein in hair follicle stem cells induces hair follicle stem cells in telogen to anagen, promoting their proliferation and activating hair follicle stem cells to promote their differentiation. As a result of the activation of hair follicle stem cells, the proportion of hair matrix cells increases.

[0005] Hair growth agents are known as therapeutic agents for baldness and male pattern baldness. Various substances are known as active ingredients of hair growth agents, among which are unsaturated fatty acids. That is, hair growth agents containing unsaturated fatty acids as active ingredients are known (see, for example, Patent Document 1 and Non-Patent Document 3).

[0006] On the other hand, royal jelly is a naturally occurring substance containing various unsaturated fatty acids, and it is known that 10-hydroxy-2-decenoic acid and 10-hydroxydecanoic acid contained in royal jelly are effective in improving female pattern hair loss (see, for example, Patent Document 2).

[0007] JP 2017-81962 A Patent No. 6808737

[0008] Plikus MV et al., Nature. 2008 Jan 17;451(7176):340-4.Lim X et al., Proc Natl Acad Sci US A. 2016 Mar 15;113(11): E1498-505.Brotzu G et al., Dermatol Ther. 2019 Jan;32(1):e12778.

[0009] The compounds described in Patent Documents 1 and 2 and Non-Patent Document 3 are useful for treating or improving baldness, male pattern baldness, and female pattern baldness. However, these documents do not state that the active ingredients described in these documents can activate hair follicle stem cells.

[0010] Furthermore, little is known about naturally occurring, safe components that can activate hair follicle stem cells.

[0011] Therefore, an object of the present invention is to provide a composition for activating hair follicle stem cells, which contains as an active ingredient a naturally occurring, recognized safe ingredient capable of activating hair follicle stem cells.Furthermore, an object of the present invention is to provide a composition for inhibiting the expression of the wnt3 gene in hair follicle stem cells and a composition for inhibiting the expression of the bmp4 gene in hair follicle stem cells, which are capable of activating hair follicle stem cells.

[0012] The present inventors have conducted extensive research to solve the above problems, and have tried many ingredients, either alone or in appropriate combinations, through trial and error in an attempt to obtain an active ingredient that activates hair follicle stem cells.

[0013] After extensive investigations, they finally found that a combination of 10-hydroxy-2-decenoic acid and 2-decenedioic acid can activate hair follicle stem cells through their inhibitory effects on the expression of the wnt3 gene and bmp4 gene in hair follicle stem cells. 10-hydroxy-2-decenoic acid and 2-decenedioic acid are components contained in royal jelly and are recognized as safe.

[0014] Based on these findings, the present inventors have succeeded in creating a composition for activating hair follicle stem cells, which contains active ingredients that are naturally derived and recognized as safe, in order to solve the problems of the present invention. The present invention has been completed based on these findings and successful examples first discovered by the present inventors.

[0015] Therefore, each aspect of the present invention provides the following embodiments: [1] A composition for activating hair follicle stem cells, comprising at least one first active ingredient selected from the group consisting of 10-hydroxy-2-decenoic acid and its derivatives and salts thereof, and at least one second active ingredient selected from the group consisting of 2-decenedioic acid and its derivatives and salts thereof. [2] A composition for inhibiting the expression of the wnt3 gene in hair follicle stem cells or a composition for inhibiting the expression of the bmp4 gene in hair follicle stem cells, comprising at least one first active ingredient selected from the group consisting of 10-hydroxy-2-decenoic acid and its derivatives and salts thereof, and at least one second active ingredient selected from the group consisting of 2-decenedioic acid and its derivatives and salts thereof. [3] The composition according to [1] or [2], which is a food or drink, cosmetic, quasi-drug, or pharmaceutical. [4] A method for activating hair follicle stem cells, comprising applying to a subject at least one first active ingredient selected from the group consisting of 10-hydroxy-2-decenoic acid, its derivatives, and salts thereof, and at least one second active ingredient selected from the group consisting of 2-decenedioic acid, its derivatives, and salts thereof, to activate the hair follicle stem cells of the subject. [5] A method for suppressing expression of the wnt3 gene in hair follicle stem cells, comprising applying to a subject at least one first active ingredient selected from the group consisting of 10-hydroxy-2-decenoic acid, its derivatives, and salts thereof, and at least one second active ingredient selected from the group consisting of 2-decenedioic acid, its derivatives, and salts thereof, to suppress the expression of the wnt3 gene in the hair follicle stem cells of the subject. [6] A method for suppressing the expression of the bmp4 gene in hair follicle stem cells, comprising applying to a subject at least one first active ingredient selected from the group consisting of 10-hydroxy-2-decenoic acid, derivatives thereof, and salts thereof, and at least one second active ingredient selected from the group consisting of 2-decenedioic acid, derivatives thereof, and salts thereof, to the subject, thereby suppressing the expression of the bmp4 gene in the hair follicle stem cells of the subject.[7] Use of at least one first active ingredient selected from the group consisting of 10-hydroxy-2-decenoic acid and derivatives thereof and salts thereof, and at least one second active ingredient selected from the group consisting of 2-decenedioic acid and derivatives thereof and salts thereof, for the manufacture of a composition for at least one effect selected from the group consisting of hair follicle stem cell activation, suppression of wnt3 gene expression in hair follicle stem cells, and suppression of bmp4 gene expression in hair follicle stem cells. [8] The use according to [7], wherein the composition is a food or beverage, cosmetic, quasi-drug, or pharmaceutical.

[0016] According to the present invention, hair follicle stem cells can be activated through the suppression of WNT3 gene expression and BMP4 gene expression in hair follicle stem cells. Furthermore, the compositions for activating hair follicle stem cells, for suppressing WNT3 gene expression in hair follicle stem cells, and for suppressing BMP4 gene expression in hair follicle stem cells according to one embodiment of the present invention are highly safe because their active ingredients are related to components contained in naturally occurring royal jelly and their metabolites. Thus, the compositions for activating hair follicle stem cells, for suppressing WNT3 gene expression in hair follicle stem cells, and for suppressing BMP4 gene expression in hair follicle stem cells according to one embodiment of the present invention can be used for hair follicle stem cell activation in various forms, such as foods and beverages, cosmetics, pharmaceuticals, and quasi-drugs.

[0017] Figure 1 shows the results of evaluation of the inhibitory effect on the expression of the Wnt3 gene, as described in the Examples below. Figure 2 shows the results of evaluation of the inhibitory effect on the expression of the Bmp4 gene, as described in the Examples below.

[0018] Each aspect of the present invention will be described in detail below, but the present invention is not limited to the details of these items and can take various forms as long as the object of the present invention is achieved.

[0019] Unless otherwise specified, the terms used in this specification are used in the sense commonly used by those skilled in the art of foods and beverages, cosmetics, pharmaceuticals, and quasi-drugs, and should not be construed as having an unduly restrictive meaning. Furthermore, the speculations and theories made in this specification are based on the inventors' knowledge and experience to date, and therefore the present invention is not limited solely to such speculations and theories.

[0020] The term "composition" is not particularly limited to the commonly used meaning, and examples thereof include a combination of two or more ingredients. "Component" refers to a substance used (added) in producing a composition, and is synonymous with substance and (raw) material. In a composition, a component may exist in a state that is maintained or changed qualitatively and / or quantitatively compared to before use. "Content" is synonymous with concentration and amount added (amount used), and refers to the ratio of the amount of a component to the total amount of a composition. However, the total amount of component content does not exceed 100%. When a commercially available product is used, the component content is preferably the amount of the component contained in the commercially available product, but may also be the amount of the commercially available product itself. "Food and beverage" is a comprehensive term meaning food products, beverages, or both. The terms "comprise," "contain," and "include" mean that elements other than those explicitly stated as included may be added (equivalent to "comprise at least"), but also encompass "consist of" and "essentially consist of." That is, "comprise" can mean including the explicitly stated elements and any one or more elements, consisting of the explicitly stated elements, or essentially consisting of the explicitly stated elements. Elements include components, steps, conditions, parameters, and other limitations. "And / or" means any one of the listed related items, or any or all combinations of two or more. The term "to" in a numerical range includes both the preceding and following numerical values, and also includes ranges excluding either of the included limits. For example, "0% to 100%" can mean 0% or more, 100% or less, or 0% or more and 100% or less. "About" means an amount within ±10% of the quantity that follows the term. For example, "about 100" means 100 ±10%, i.e., 90-110.

[0021] The term "hair follicle stem cell" is not particularly limited to the commonly used meaning, but refers, for example, to epithelial stem cells that are present mainly in the bulge region of hair follicles and have the ability to differentiate into hair matrix cells. "Activation of hair follicle stem cells" refers to any one, two, or all three of the following events: promoting hair follicle stem cell differentiation, promoting hair follicle stem cell proliferation, and inducing hair follicle stem cells in telogen phase to anagen phase through the inhibitory effect on the expression of the wnt3 gene and bmp4 gene in hair follicle stem cells. Therefore, the composition of one embodiment of the present invention can also be used as a composition for promoting hair follicle stem cell differentiation, a composition for promoting hair follicle stem cell proliferation, and / or a composition for inducing telogen phase hair follicle stem cells in anagen phase. "Gene expression inhibitory effect" refers to at least one action selected from the group consisting of reducing the expression level of a gene (i.e., the amount of mRNA), reducing the translation level of a gene product (protein) (i.e., the amount of protein), and inhibiting the production of a gene product.

[0022] [Summary of the Invention] One aspect of the present invention is a composition for activating hair follicle stem cells, used to activate hair follicle stem cells. Another aspect of the present invention is a composition for inhibiting the expression of the Wnt3 gene in hair follicle stem cells, used to inhibit the expression of the Wnt3 gene in hair follicle stem cells. Another aspect of the present invention is a composition for inhibiting the expression of the BMP4 gene in hair follicle stem cells, used to inhibit the expression of the BMP4 gene in hair follicle stem cells. The composition for activating hair follicle stem cells, the composition for inhibiting the expression of the Wnt3 gene in hair follicle stem cells, and the composition for inhibiting the expression of the BMP4 gene in hair follicle stem cells according to one aspect of the present invention are characterized by comprising two active ingredients. The first active ingredient is at least one ingredient selected from the group consisting of 10-hydroxy-2-decenoic acid, derivatives thereof, and salts thereof. The second active ingredient is at least one ingredient selected from the group consisting of 2-decenedioic acid, derivatives thereof, and salts thereof. In this specification, the first active ingredient and the second active ingredient may be collectively referred to as the active ingredients. The composition for activating hair follicle stem cells, the composition for inhibiting the expression of the wnt3 gene in hair follicle stem cells, and the composition for inhibiting the expression of the bmp4 gene in hair follicle stem cells of one embodiment of the present invention are preferably not used for the treatment or prevention of female pattern baldness.Furthermore, the composition for activating hair follicle stem cells, the composition for inhibiting the expression of the wnt3 gene in hair follicle stem cells, and the composition for inhibiting the expression of the bmp4 gene in hair follicle stem cells of one embodiment of the present invention preferably do not contain unsaturated fatty acids other than the active ingredient.

[0023] The wnt3 gene is a gene that encodes the Wnt3 protein, which is one of the proteins that constitute the commonly known Wnt signaling pathway. The bmp4 gene is a gene that encodes the Bmp4 protein, which is one of the proteins that constitute the commonly known Bmp signaling pathway. Specific examples of the wnt3 gene and bmp4 gene include the human wnt3 gene registered under accession number NM_030753.5 and the human bmp4 gene registered under accession number NM_001202.6.

[0024] Hair follicle stem cells in the telogen phase hardly proliferate or differentiate, and express relatively high amounts of the wnt3 and bmp4 genes. In contrast, hair follicle stem cells in the anagen phase actively proliferate and differentiate, and express relatively low amounts of the wnt3 and bmp4 genes. Thus, when the expression levels of the wnt3 and bmp4 genes decrease, hair follicle stem cells transition from the telogen phase to the anagen phase, and begin to proliferate and differentiate (see, for example, Maksim V. Plikus et al., Nature. 2008 January 17; 451(7176): 340-344. doi:10.1038 / nature06457; Krzysztof Kobielak et al., PNAS June 12, 2007, vol. 104, no. 24, 10063-10068). As described in the Examples below, the active ingredient suppresses the expression of the wnt3 gene and the bmp4 gene in hair follicle stem cells. As a result, hair follicle stem cells that were in the telogen phase are induced to enter the anagen phase, where they proliferate and differentiate. Therefore, the active ingredient's inhibitory effect on the expression of the wnt3 gene and the bmp4 gene in hair follicle stem cells activates hair follicle stem cells, causing them to be induced from the telogen phase to the anagen phase, where they proliferate and differentiate. Through these phenomena, the present invention, by containing the active ingredient, can take the form of a composition for activating hair follicle stem cells, a composition for inhibiting the expression of the wnt3 gene in hair follicle stem cells, and a composition for inhibiting the expression of the bmp4 gene in hair follicle stem cells.

[0025] [Active ingredient] 10-hydroxy-2-decenoic acid is, as is commonly known, a compound represented by the following formula (I): (I) is a compound having a structure represented by the formula:

[0026] 2-Decenedioic acid can be prepared by the conventional method represented by the following formula (II): (II) is a compound having a structure represented by the formula:

[0027] 10-hydroxy-2-decenoic acid is metabolized in the human body and converted to 2-decenedioic acid. As the 10-hydroxy-2-decenoic acid, 10-hydroxy-2-decenoic acid itself may be used, or a 10-hydroxy-2-decenoic acid-containing product containing 10-hydroxy-2-decenoic acid may be used. Similarly, as the 2-decenedioic acid, 2-decenedioic acid itself may be used, or a 2-decenedioic acid-containing product containing 2-decenedioic acid may be used. When using 10-hydroxy-2-decenoic acid itself and / or 2-decenedioic acid itself, commercially available products may be used, or products chemically synthesized by known methods or extracted from natural products may be used.

[0028] The 10-hydroxy-2-decenoic acid-containing material and the 2-decenedioic acid-containing material are not particularly limited as long as they contain 10-hydroxy-2-decenoic acid and 2-decenedioic acid, respectively. Examples thereof include royal jelly, which contains both 10-hydroxy-2-decenoic acid and 2-decenedioic acid.

[0029] Royal jelly is a milky white gel-like substance produced by honeybee worker bees that are 3 to 12 days old, by mixing secretions from the hypopharyngeal and mandibular glands. The main physiologically active components in royal jelly include organic acids such as saturated and unsaturated fatty acids that are unique to royal jelly, as well as proteins, amino acids, peptides, lipids, sugars, vitamin B, folic acid, nicotinic acid, pantothenic acid, and other vitamins, and various minerals.

[0030] Royal jelly includes fresh royal jelly, dried royal jelly, dried royal jelly powder, enzyme-treated royal jelly, royal jelly extract, royal jelly fermentation product, etc. Royal jelly may be produced in any of Europe, Oceania, America, Brazil, Japan, China, other Asian countries, etc.

[0031] Dried royal jelly powder is obtained by drying and powdering fresh royal jelly. As a drying method, any known method employed in general food processing can be used, such as natural drying such as ventilation drying or sun drying, forced drying in which heating is performed by electricity or the like, or freeze-drying. Freeze-drying is preferred.

[0032] Enzyme-treated royal jelly is royal jelly treated with a protease. Preferably, it is hypoallergenic enzyme-treated royal jelly, in which allergic reactions caused by proteins contained in royal jelly are suppressed by protease treatment. Therefore, in addition to protease-decomposed products of proteins contained in royal jelly, enzyme-treated royal jelly may contain organic acids such as the saturated fatty acids and unsaturated fatty acids described above, lipids, sugars, vitamins, and various minerals.

[0033] The royal jelly used to produce enzyme-treated royal jelly is not particularly limited, and examples include raw royal jelly, royal jelly powder obtained by drying and powdering raw royal jelly, and raw royal jelly extracted with water or aqueous ethanol.

[0034] Enzyme-treated royal jelly can be produced by treating royal jelly raw materials with an enzyme having at least endopeptidase activity, an enzyme having at least exopeptidase activity, and / or an enzyme having both endopeptidase activity and exopeptidase activity.

[0035] Examples of proteolytic enzymes having at least endopeptidase activity include endopeptidases derived from animals (e.g., trypsin, chymotrypsin, etc.), plants (e.g., papain, etc.), and microorganisms (e.g., lactic acid bacteria, yeast, mold, Bacillus subtilis, actinomycetes, etc.).

[0036] Examples of proteolytic enzymes having at least exopeptidase activity include carboxypeptidase, aminopeptidase, exopeptidases derived from microorganisms (e.g., lactic acid bacteria, Aspergillus, Rhizopus, etc.), and pancreatin and pepsin, which also have endopeptidase activity.

[0037] Among these various enzymes, preferred examples of enzymes having both exopeptidase activity and endopeptidase activity include peptidase produced by Streptomyces griseus (trade name: Actinase AS), peptidase produced by Aspergillus oryzae (trade name: Protease A, Flavorzyme, Proteax), and peptidase produced by Aspergillus melleus (trade name: Protease P). Also, preferred examples of enzymes having exoprotease activity include peptidase produced by Aspergillus oryzae (trade name: Umamizyme G, Promod 192P, Promod 194P, Sumizyme FLAP), peptidase produced by Aspergillus sojae (trade name: Sternzyme B15024), peptidase produced by the genus Aspergillus (trade name: Coclase P), and peptidase produced by Rhizopus oryzae (trade name: Peptidase R). Further, preferred examples of enzymes having endoprotease activity include peptidases produced by Bacillus subtilis (trade names: Orientase 22BF, Nucleicin), peptidases produced by Bacillus licheniformis (trade name: Alcalase), peptidases produced by Bacillus stearothermophilus (trade name: Protease S), peptidases produced by Bacillus amyloliquefaciens (trade name: Neutrase), and peptidases produced by the genus Bacillus (trade name: Protamex).

[0038] Enzyme treatment to reduce the allergenicity of royal jelly can be carried out according to the description in, for example, Japanese Patent Application Laid-Open Nos. 2007-295919 and 2007-295920.

[0039] Royal jelly extract is obtained by extracting royal jelly (including raw, dried and crushed royal jelly) with water or aqueous ethanol.

[0040] The royal jelly fermented product can be produced by a conventional method using microorganisms such as yeast and lactic acid bacteria.

[0041] Commercially available royal jelly may be used, such as Enzyme-Hydrolyzed Royal Jelly King (manufactured by Yamada Bee Farm), Royal Jelly FD Powder (manufactured by Nakahara Co., Ltd.), Royal Jelly Extract SF (manufactured by Matsuura Pharmaceutical Co., Ltd.), Deproteinized Royal Jelly Powder F (manufactured by Maruzen Pharmaceutical Co., Ltd.), and Deproteinized Royal Jelly Extract (manufactured by API Pharmaceuticals).

[0042] As described above, 10-hydroxy-2-decenoic acid and 2-decenedioic acid are both types of fatty acids contained in royal jelly. 10-hydroxy-2-decenoic acid and 2-decenedioic acid may be synthetic products or may be derived from natural products such as royal jelly. 10-hydroxy-2-decenoic acid and 2-decenedioic acid derived from royal jelly can be obtained, for example, by extraction and purification from royal jelly using an organic solvent or the like. 10-hydroxy-2-decenoic acid and 2-decenedioic acid may be cis or trans.

[0043] The derivatives of 10-hydroxy-2-decenoic acid and 2-decenedioic acid are not particularly limited as long as they have the effect of suppressing the expression of the wnt3 gene and the bmp4 gene in hair follicle stem cells, and examples include their chlorides, esters, amides, acid anhydrides, glycosides, etc. The derivatives of 10-hydroxy-2-decenoic acid and 2-decenedioic acid may be synthesized from 10-hydroxy-2-decenoic acid and 2-decenedioic acid by a method known to date, or may be obtained by extraction and purification from natural products such as royal jelly using an organic solvent, etc.

[0044] 10-Hydroxy-2-decenoic acid and derivatives thereof, and 2-decenedioic acid and derivatives thereof may be in the form of a salt. These salts are not particularly limited as long as they have the effect of suppressing the expression of the wnt3 gene and the bmp4 gene in hair follicle stem cells. Examples of such salts include alkali metal salts such as sodium salts and potassium salts; alkaline earth metal salts such as calcium salts and magnesium salts; ammonium salts; aliphatic amine salts such as trimethylamine salts, triethylamine salts, cyclohexylamine salts, ethanolamine salts, diethanolamine salts, triethanolamine salts, and procaine salts; aralkylamine salts such as N,N-dibenzylethylenediamine; heterocyclic aromatic amine salts such as pyridine salts, picoline salts, quinoline salts, and isoquinoline salts; tetramethylammonium salts, tetraethylamine salts, and tetraethylamine salts. quaternary ammonium salts such as ammonium salt, benzyltrimethylammonium salt, benzyltributylammonium salt, methyltrioctylammonium salt, and tetrabutylammonium salt; amino acid salts such as arginine salt, lysine salt, histidine salt, arginine salt, aspartate, and glutamate; inorganic acid salts such as hydrochloride, sulfate, nitrate, phosphate, carbonate, bicarbonate, and perchlorate; organic acid salts such as acetate, propionate, lactate, maleate, fumarate, tartrate, malate, citrate, and ascorbate; and sulfonate salts such as methanesulfonate, isethionate, benzenesulfonate, and p-toluenesulfonate.

[0045] [Composition for activating hair follicle stem cells] The composition for activating hair follicle stem cells of one embodiment of the present invention contains an active ingredient, thereby activating hair follicle stem cells.

[0046] The content of the active ingredient in the composition for activating hair follicle stem cells of one embodiment of the present invention is not particularly limited as long as the composition for activating hair follicle stem cells of one embodiment of the present invention has the effect of suppressing the expression of the wnt3 gene and the bmp4 gene in hair follicle stem cells. However, the content of the active ingredient in the composition for activating hair follicle stem cells of one embodiment of the present invention is, for example, any of the following lower and upper limits, or a combination of the lower and upper limits, in terms of solid content relative to the total amount of the composition for activating hair follicle stem cells: the lower limit is 0.1% by mass or more, 1% by mass or more, 3% by mass or more, 3.5% by mass or more, 5% by mass or more, 7% by mass or more, 10% by mass or more, 15% by mass or more, 20% by mass or more, 25% by mass or more, 30% by mass or more, 35% by mass or more, 40% by mass or more, 45% by mass or more, 50% by mass or more, 55% by mass or more, 60% by mass or more. , 65% by mass or more, 70% by mass or more, 75% by mass or more, 80% by mass or more, 85% by mass or more, 90% by mass or more, 93% by mass or more, 95% by mass or more, 98% by mass or more, 99% by mass or more or 100% by mass; and the upper limit is 100% by mass or less, 99% by mass or less, 98% by mass or less, 95% by mass or less, 93% by mass or less, 90% by mass or less, 85% by mass or more. Lower, 80% by mass or less, 75% by mass or less, 70% by mass or less, 65% by mass or less, 60% by mass or less, 55% by mass or less, 50% by mass or less, 45% by mass or less, 40% by mass or less, 35% by mass The content may be 30% by mass or less, 25% by mass or less, 20% by mass or less, 15% by mass or less, 10% by mass or less, 8% by mass or less, 5% by mass or less, 3% by mass or less, or 1% by mass or less.

[0047] The content of the active ingredients is the total amount of the first active ingredient and the second active ingredient. Because both the first active ingredient and the second active ingredient have the effect of suppressing the expression of the wnt3 gene and the bmp4 gene in hair follicle stem cells, the ratio of the content of the first active ingredient to the content of the second active ingredient in the active ingredient content is not particularly limited and may be set as appropriate. However, for example, because the effect of 10-hydroxy-2-decenoic acid on the expression of the wnt3 gene and the bmp4 gene in hair follicle stem cells is comparable to or greater than that of 2-decenedioic acid, the content of the first active ingredient is preferably comparable to or greater than the content of the second active ingredient, and more preferably the content of the first active ingredient is greater than the content of the second active ingredient.

[0048] The subject of application of the composition for activating hair follicle stem cells of one embodiment of the present invention is not particularly limited, and examples thereof include animals, particularly mammals. Mammals include humans, dogs, cats, cows, horses, pigs, sheep, and rabbits, with humans being preferred. The subject may be a healthy subject, but is preferably a subject in which activation of hair follicle stem cells is desired. Mammalian hair follicles shrink with age, regardless of gender (see, for example, Hiroyuki Matsumura et al., Science, Vol. 351, ISSUE 6273, p. 575). Furthermore, hair follicle stem cells are maintained at the onset of androgenetic alopecia. From this perspective, the age and gender of the subject are not particularly limited, and examples include adults, preferably middle-aged to elderly men and women, preferably men, and more preferably men in the early stages of androgenetic alopecia.

[0049] The route of administration of the composition for activating hair follicle stem cells according to one embodiment of the present invention is not particularly limited, and may be oral or parenteral. Oral administration includes enteral administration, and parenteral administration includes topical administration, such as transdermal administration.

[0050] The dosage of the composition for activating hair follicle stem cells when administered orally according to one embodiment of the present invention can be determined as appropriate depending on the active ingredient, the form of the composition, and the application method and amount. For example, when the active ingredient is in the form of royal jelly as a 10-hydroxy-2-decenoic acid-containing product and a 2-decenedioic acid-containing product, the amount of active ingredient, calculated as dry solids, per day for an adult weighing 60 kg is preferably 10 mg to 30,000 mg, more preferably 100 mg to 20,000 mg, 150 mg to 15,000 mg, 600 mg to 12,000 mg, 1,200 mg to 10,000 mg, or 2,400 mg to 8,000 mg. The dosage can be increased or decreased as appropriate depending on factors such as the health condition of the subject, the method of administration, the type of active ingredient, and the combination with other agents.

[0051] When the active ingredient is 10-hydroxy-2-decenoic acid or a derivative thereof, or a salt thereof, the dosage of the composition for activating hair follicle stem cells of one embodiment of the present invention is, for example, preferably 1 mg to 200 mg, and more preferably 10 mg to 100 mg, of the total amount of active ingredient, calculated on dry solids, per day for an adult weighing 60 kg. Furthermore, when the active ingredient is 2-decenedioic acid or a derivative thereof, or a salt thereof, the dosage of the composition for activating hair follicle stem cells of one embodiment of the present invention is, for example, preferably 0.1 mg to 30 mg, and more preferably 1 mg to 15 mg, of the total amount of active ingredient, calculated on dry solids, per day for an adult weighing 60 kg. The dosage can be increased or decreased as appropriate depending on factors such as the health condition of the subject, the method of administration, the type of active ingredient, and the combination with other agents.

[0052] The composition for activating hair follicle stem cells of one embodiment of the present invention may be administered once a day or in divided doses, such as twice or three times a day, as long as the effective daily dose is within the above-mentioned range. The composition for activating hair follicle stem cells of one embodiment of the present invention is preferably administered continuously or intermittently, and more preferably, for example, for one to four weeks, one month or more, six months or more, or one year or more.

[0053] When a composition for activating hair follicle stem cells according to one embodiment of the present invention is administered parenterally, the dosage may vary depending on the active ingredient, the area to which it is applied, and the range of application. For example, when the active ingredient is royal jelly, the amount to be applied to the skin is preferably 0.01 mg to 50 mg of the active ingredient, more preferably 0.02 mg to 40 mg, and even more preferably 0.02 mg to 35 mg, or 0.025 mg to 30 mg.

[0054] When the active ingredient is 10-hydroxy-2-decenoic acid or a derivative thereof, or a salt thereof, the dosage of the composition for activating hair follicle stem cells of one embodiment of the present invention to be applied to the skin is, for example, preferably 0.001 mg to 0.3 mg, and more preferably 0.01 mg to 0.1 mg, of the total amount of the active ingredient. Also, when the active ingredient is 2-decenedioic acid or a derivative thereof, or a salt thereof, the dosage of the composition for activating hair follicle stem cells of one embodiment of the present invention to be applied to the skin is, for example, preferably 0.0001 mg to 0.05 mg, and more preferably 0.001 mg to 0.04 mg, of the total amount of the active ingredient.

[0055] The composition for activating hair follicle stem cells according to one embodiment of the present invention may contain other ingredients in addition to the active ingredient. The other ingredients are not particularly limited as long as they do not interfere with the solution of the problems of the present invention, and may include, for example, powder ingredients, liquid oils and fats, solid oils and fats, waxes, hydrocarbon oils, higher fatty acids, higher alcohols, ester oils, silicone oils, anionic surfactants, cationic surfactants, amphoteric surfactants, nonionic surfactants, moisturizers, water-soluble polymers, thickeners, film-forming agents, UV absorbers, sequestering agents, lower alcohols, polyhydric alcohols, sugars, amino acids, organic amines, polymer emulsions, pH adjusters, skin nutrients, vitamins, antioxidants, antioxidant aids, fragrances, water, preservatives (e.g., ethylparaben, butylparaben), anti-inflammatory agents (e.g., glycyrrhizinic acid derivatives, glycyrrhetinic acid derivatives, salicylic acid derivatives, hinokitiol, zinc oxide, allantoin), whitening agents (e.g., placenta extract, saxifrage extract, arbutin), various extracts (e.g., Phellodendron bark, Coptis chinensis, Lithospermum root, Peony root, Swertia japonica, birch, sey Root, loquat, carrot, aloe, mallow, iris, grape, coix seed, loofah, lily, saffron, cnidium, ginger, St. John's wort, ononis, garlic, chili pepper, tangerine, angelica, seaweed, etc.), activators (photosensitizers, cholesterol derivatives, etc.), blood circulation promoters (nonylic acid valenylamide, nicotinic acid benzyl ester, nicotinic acid β-butoxyethyl ester, capsaicin, zingerone, cantharides tincture, Examples of anti-inflammatory agents include ichthammol, tannic acid, α-borneol, tocopherol nicotinate, inositol hexanicotinate, cyclandelate, cinnarizine, tolazoline, acetylcholine, verapamil, cepharanthine, γ-oryzanol, etc.), antiseborrheic agents (sulfur, thianthol), anti-inflammatory agents (tranexamic acid, thiotaurine, hypotaurine), beekeeping products (propolis, honey, honeycomb, beeswax, pollen, bee venom, etc.).

[0056] The hair follicle stem cell activation composition of one embodiment of the present invention can be prepared by mixing the active ingredient with one or more other ingredients and using conventional methods to obtain a desired form. The form of the hair follicle stem cell activation composition of one embodiment of the present invention is not particularly limited as long as it exhibits the inhibitory effect of the active ingredient on the expression of the wnt3 gene and the bmp4 gene in hair follicle stem cells, and examples of the form of the composition include solid, liquid, gel, suspension, cream, sheet, stick, powder, granule, tablet, rod, plate, block, paste, capsule, caplet, aerosol, and foam.

[0057] The composition for activating hair follicle stem cells according to one embodiment of the present invention may be a packaged composition filled in a sealable airtight or hermetically sealed container. The container is not particularly limited as long as it is an airtight or hermetically sealed container, but examples include packaging containers such as single-layer or laminated film bags, retort pouches, vacuum packs, molded containers, bottles, and cans made from metals such as aluminum and steel, paper, plastics such as PET, and glass. Packaged compositions can be sold independently and commercially available. Note that lidded containers used for storing food at home are hermetically sealed containers, and are strictly distinguished from airtight containers and hermetically sealed containers, particularly hermetically sealed containers.

[0058] The hair follicle stem cell activation effect of the hair follicle stem cell activation composition of one embodiment of the present invention can be confirmed by confirming the suppression of wnt3 gene expression and bmp4 gene expression in hair follicle stem cells. Thus, the hair follicle stem cell activation effect of the hair follicle stem cell activation composition of one embodiment of the present invention may be, for example, to the extent that the expression of wnt3 gene in hair follicle stem cells and the expression of bmp4 gene in hair follicle stem cells are suppressed compared to a composition (control) that does not contain the active ingredient under the same conditions.

[0059] [Composition for inhibiting the expression of the wnt3 gene in hair follicle stem cells and composition for inhibiting the expression of the bmp4 gene in hair follicle stem cells] A composition for inhibiting the expression of the wnt3 gene in hair follicle stem cells according to one embodiment of the present invention comprises an active ingredient, thereby being able to inhibit the expression of the wnt3 gene in hair follicle stem cells. A composition for inhibiting the expression of the bmp4 gene in hair follicle stem cells according to one embodiment of the present invention comprises an active ingredient, thereby being able to inhibit the expression of the bmp4 gene in hair follicle stem cells.

[0060] For the composition for inhibiting the expression of the wnt3 gene in hair follicle stem cells according to one embodiment of the present invention and the composition for inhibiting the expression of the bmp4 gene in hair follicle stem cells according to one embodiment of the present invention, the type and amount of active ingredient, the method and amount of administration, the components contained, the shape, the manufacturing method, etc., please refer to the section above titled ``Composition for activating hair follicle stem cells.''

[0061] The effect of the composition for inhibiting the expression of the wnt3 gene in hair follicle stem cells of one embodiment of the present invention on inhibiting the expression of the wnt3 gene in hair follicle stem cells may be to the same extent that the expression of the wnt3 gene in hair follicle stem cells is suppressed compared to a composition (control) that does not contain an active ingredient under the same conditions.Similarly, the effect of the composition for inhibiting the expression of the bmp4 gene in hair follicle stem cells of one embodiment of the present invention on inhibiting the expression of the bmp4 gene in hair follicle stem cells may be to the same extent that the expression of the bmp4 gene in hair follicle stem cells is suppressed compared to a composition (control) that does not contain an active ingredient under the same conditions.

[0062] The effect of suppressing the expression of the wnt3 gene in hair follicle stem cells can be confirmed by the method described in the Examples below. For example, a composition for suppressing the expression of the wnt3 gene in hair follicle stem cells according to one aspect of the present invention preferably has the effect of suppressing the expression of the wnt3 gene in hair follicle stem cells such that the expression level of the wnt3 gene in hair follicle stem cells is 90% or less, and more preferably such that the expression level of the wnt3 gene in hair follicle stem cells is 85% or less, relative to a control in which DMSO is used instead of the active ingredient, by the method described in the Examples below.

[0063] The effect of suppressing bmp4 gene expression in hair follicle stem cells can be confirmed by the method described in the Examples below. For example, a composition for suppressing bmp4 gene expression in hair follicle stem cells according to one embodiment of the present invention preferably has the effect of suppressing bmp4 gene expression in hair follicle stem cells such that the expression level of the bmp4 gene is 90% or less, more preferably such that the expression level of the bmp4 gene is 80% or less, and even more preferably such that the expression level of the bmp4 gene is 75% or less, relative to a control using DMSO instead of the active ingredient, by the method described in the Examples below.

[0064] [Foods and beverages, cosmetics, quasi-drugs and pharmaceuticals] The composition for activating hair follicle stem cells, the composition for inhibiting the expression of the wnt3 gene in hair follicle stem cells and the composition for inhibiting the expression of the bmp4 gene in hair follicle stem cells according to one embodiment of the present invention can be used as foods and beverages (particularly foods and beverages intended for health, maintaining or improving health (e.g., health foods, functional foods, nutritional compositions, dietary supplements, supplements, health foods, foods for specified health uses, foods with nutrient functions or foods with functional claims)), cosmetics, quasi-drugs, pharmaceuticals and the like. Therefore, another aspect of the present invention is a food, beverage, cosmetic, quasi-drug or pharmaceutical that comprises or is the composition for activating hair follicle stem cells, the composition for inhibiting the expression of the wnt3 gene in hair follicle stem cells and the composition for inhibiting the expression of the bmp4 gene in hair follicle stem cells according to one embodiment of the present invention.

[0065] The content of the active ingredient in the food and beverage products, cosmetics, quasi-drugs and pharmaceuticals of one embodiment of the present invention is not particularly limited, and may be an effective amount that can achieve the oral or parenteral administration dose of the composition for activating hair follicle stem cells, the composition for inhibiting the expression of the wnt3 gene in hair follicle stem cells and the composition for inhibiting the expression of the bmp4 gene in hair follicle stem cells.

[0066] When the food and beverage products, cosmetics, quasi-drugs and pharmaceuticals of one embodiment of the present invention contain as one component a composition for activating hair follicle stem cells, a composition for inhibiting the expression of the wnt3 gene in hair follicle stem cells and a composition for inhibiting the expression of the bmp4 gene in hair follicle stem cells of one embodiment of the present invention, they can be produced, for example, by adding a composition for activating hair follicle stem cells, a composition for inhibiting the expression of the wnt3 gene in hair follicle stem cells and a composition for inhibiting the expression of the bmp4 gene in hair follicle stem cells of one embodiment of the present invention to an intermediate product in the manufacturing process of these products.

[0067] In addition to the active ingredient, the cosmetic product of one embodiment of the present invention can be appropriately blended with ingredients typically used in cosmetics, such as disinfectants, preservatives, surfactants, alcohols, aqueous components, water, colorants, pH adjusters, solubilizers, abrasives, foaming agents, enzymes, flavoring agents, chelating agents, excipients, thickeners, bases, emulsifiers, solvents, stabilizers, oils, cleaning agents (lactic acid bacteria), whitening agents, moisturizers, antioxidants, UV absorbers, powder components, coloring materials, and various skin nutrients, as needed.

[0068] The cosmetic raw material may be in any form, such as a solid, liquid, or paste. The cosmetic may be a medicated cosmetic (i.e., a quasi-drug). The cosmetic includes any cosmetic that can be applied to the skin, mucous membranes, body hair, head hair, scalp, nails, teeth, facial skin, lips, and other areas of animals (including humans).

[0069] Cosmetics can take a wide range of formulations, including aqueous solutions, solubilized solutions, emulsions, powders, oils, gels, ointments, aerosols, water-oil two-layer systems, and water-oil-powder three-layer systems.

[0070] The use of the cosmetics is also arbitrary, and examples thereof include basic cosmetics such as facial cleansers, lotions, emulsions, creams, gels, essences, beauty serums, packs, masks, mists, and UV protection cosmetics; makeup cosmetics such as foundations, lipsticks, blushers, eye shadows, eyeliners, and mascaras; nail cosmetics such as nail polish, base coats, top coats, and nail polish removers; and other examples include facial cleansers, (paste or liquid) dentifrices, mouth rinses, oral cosmetics, massage agents, cleansing agents, aftershave lotions, pre-shave lotions, shaving creams, body soaps, soaps, shampoos, rinses, hair treatments, hair styling products, hair tonics, hair mists, hair foams, hair liquids, hair gels, hair sprays, hand creams, hand soaps, hair growth agents, antiperspirants, and bath additives.

[0071] In addition to the active ingredient, the food and beverage of one embodiment of the present invention may contain ingredients that are normally used in food and beverage, such as minerals, vitamins, flavonoids, quinones, polyphenols, amino acids, nucleic acids, essential fatty acids, cooling agents, binders, sweeteners, disintegrants, lubricants, colorants, flavorings, stabilizers, gelling agents, preservatives, sustained-release regulators, surfactants, solubilizers, and humectants.

[0072] Food and drink products include all foods and drink products that can be consumed by animals (including humans). The types of foods and drink products are not particularly limited, and examples thereof include dairy products, fermented foods (such as yogurt), beverages (soft drinks such as coffee, juice, and tea drinks, dairy drinks, lactic acid bacteria drinks, lactic acid bacteria-containing drinks, yogurt drinks, carbonated drinks, sake, Western liquor, and alcoholic beverages such as fruit wine), spreads (such as custard cream), pastes (such as fruit paste), Western confectionery products (such as chocolate, donuts, pies, cream puffs, gum, gummies, jellies, candies, cookies, cakes, and puddings), Japanese confectionery products (such as daifuku, mochi, manju, castella cakes, anmitsu, and yokan), frozen desserts (such as ice cream, popsicles, and sherbet), foods (such as curry, beef bowls, rice porridge, miso soup, soup, meat sauce, pasta, pickles, and jam), and seasonings (such as dressings, sprinkles, umami seasonings, and soup bases).

[0073] The method for producing the food or drink is not particularly limited, and any known method can be used as appropriate.

[0074] A specific example of a food or drink is a supplement. The dosage unit form when used as a supplement is not particularly limited and can be selected appropriately, and examples include chewable tablets, troches, capsules, granules, liquids, powders, syrups, pastes, drinks, gummies, and the like.

[0075] The pharmaceutical product of one embodiment of the present invention can be used by mixing, in addition to the active ingredient, other medicinal ingredients such as vitamins and herbal medicines described in the Japanese Pharmacopoeia.

[0076] In one aspect of the pharmaceutical of the present invention, the active ingredient can be prepared into a pharmaceutical formulation by preparing it together with ingredients acceptable for pharmaceuticals into the form of tablets (including plain tablets, sugar-coated tablets, effervescent tablets, film-coated tablets, chewable tablets, troches, etc.), capsules, pills, powders (dispersed medicines), fine granules, granules, liquids, suspensions, emulsions, syrups, pastes, injections (including cases where the active ingredient is mixed with distilled water or an infusion such as an amino acid infusion or an electrolyte infusion at the time of use to prepare it as a liquid), etc.

[0077] Pharmaceuticals may be administered locally or systemically. There are no particular limitations on the administration method, and they may be administered orally or parenterally. Parenteral administration routes include subcutaneous, intradermal, intramuscular, intraperitoneal, intravenous or intraarterial administration, and transdermal administration.

[0078] In addition to the active ingredient, the pharmaceutical product of one embodiment of the present invention can be appropriately formulated with pharmaceutically acceptable ingredients such as ingredients normally used in pharmaceutical products, for example, excipients, binders, disintegrants, lubricants, colorants, suspending agents, thickeners, antioxidants, absorption enhancers, pH adjusters, preservatives, antiseptics, stabilizers, surfactants, sweeteners, flavoring agents, and fragrances.

[0079] Cosmetics and pharmaceuticals according to one embodiment of the present invention include quasi-drugs.

[0080] The composition for activating hair follicle stem cells, the composition for inhibiting the expression of the wnt3 gene in hair follicle stem cells, and the composition for inhibiting the expression of the bmp4 gene in hair follicle stem cells according to one embodiment of the present invention are intended for use in foods and beverages, cosmetics, pharmaceuticals, and quasi-drugs, and are therefore intended for use in mammals including humans (preferably humans). As such, the composition for activating hair follicle stem cells, the composition for inhibiting the expression of the wnt3 gene in hair follicle stem cells, and the composition for inhibiting the expression of the bmp4 gene in hair follicle stem cells according to one embodiment of the present invention are highly safe because they contain naturally occurring ingredients such as royal jelly, which has traditionally been used as a food ingredient, as their active ingredients.

[0081] Another aspect of the present invention is a method for activating hair follicle stem cells, comprising applying an active ingredient to a subject to activate the hair follicle stem cells of the subject. Another aspect of the present invention is a method for suppressing expression of the wnt3 gene in hair follicle stem cells, comprising applying an active ingredient to a subject to suppress expression of the wnt3 gene in the hair follicle stem cells of the subject. Another aspect of the present invention is a method for suppressing expression of the bmp4 gene in hair follicle stem cells, comprising applying an active ingredient to a subject to suppress expression of the bmp4 gene in the hair follicle stem cells of the subject. Another aspect of the present invention is a method for using an active ingredient to produce a composition for activating hair follicle stem cells, a composition for suppressing expression of the wnt3 gene in hair follicle stem cells, or a composition for suppressing expression of the bmp4 gene in hair follicle stem cells.

[0082] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples, and the present invention can take various forms as long as the object of the present invention can be achieved.

[0083] Using an organoid culture system of whisker tissue, the expression levels of genes involved in hair follicle stem cell activation after 72 hours were evaluated for 10-hydroxy-2-decenoic acid and 2-decenedioic acid. As a result, the expression levels of genes encoding Wnt3 protein and Bmp4 protein, which are involved in the activation of hair follicle stem cell stemness, were significantly reduced by 10-hydroxy-2-decenoic acid and 2-decenedioic acid. These results demonstrate that 10-hydroxy-2-decenoic acid and 2-decenedioic acid, through their inhibitory effects on the expression levels of the Wnt3 gene and Bmp4 gene, are responsible for hair follicle stem cell activation, such as promoting hair follicle stem cell differentiation, promoting hair follicle stem cell proliferation, and inducing hair follicle stem cells in the anagen phase.

[0084] [1. Test Sample] Four fatty acids contained in royal jelly were used. The fatty acids used were 10-hydroxydecanoic acid (manufactured by Combi-Blocks; also referred to as "decanoic acid"), 10-hydroxy-2-decenoic acid (manufactured by Hangzhou Eastbiopharm; also referred to as "decenoic acid"), 2-decenedioic acid (manufactured by Sundia Meditech; also referred to as "decenedioic acid"), and sebacic acid (manufactured by Sigma-Aldrich).

[0085] [2. Evaluation Method] Using the following method, changes in gene expression levels due to the addition of fatty acids to an organoid culture system of whisker tissue were analyzed to evaluate the effect on differentiation markers of hair follicle stem cells.

[0086] Mouse whisker hair follicles and their surrounding tissues (organoids) were collected using surgical scissors and placed in a 96-well plate at 37°C and 5% CO ２ After 24 hours of incubation, the wells were filled with 150 μl of DMEM / 10% FBS medium containing fatty acids (100 μM), antibiotics (penicillin-streptomycin-amphotericin; PSA), HEPES (10 mM), and glutamine (2 mM). The plate was incubated at 37°C and 5% CO ２ The tissue was incubated under ambient conditions and the tissue pieces were harvested after 48 hours.

[0087] Total RNA for gene expression analysis was extracted from the collected tissue fragments according to the NucleoSpin® RNA Plus XS (TakaraBio, Sharp U0990C) manual. The extracted pre-RNA was reverse transcribed using PrimeScript™ RT Master Mix (TakaraBio, Sharp RR036B) to prepare cDNA. The expression levels of each gene in the cDNA were quantified by qPCR using the primers listed in Table 1 and THUNDERBIRD® Next SYBR® qPCR Mix (TOYOBO, Sharp QPX-201). Beta-actin was used as the reference gene for this test.

[0088]

[0089] All results are shown as mean ± standard deviation. The gene expression level of each fatty acid was evaluated using Dunnett's test, in comparison with the DMSO group as a control group.

[0090] 3. Evaluation Results The quantitative results of the Wnt3 gene expression level are shown in FIG. 1, and the quantitative results of the Bmp4 gene expression level are shown in FIG. 2 (n=3 or 4, *p<0.05; vs. control).

[0091] As shown in Figures 1 and 2, when the gene expression levels of whisker tissue organoids were compared with those of the control when decenoic acid or decenedioic acid was added, it was found that the addition of decenoic acid and decenedioic acid reduced the expression levels of the Wnt3 protein and Bmp4 protein genes. In particular, it was found that the addition of decenoic acid significantly reduced the expression levels of the Wnt3 protein and Bmp4 protein genes, and the addition of decenedioic acid significantly reduced the expression level of the Bmp4 protein gene.

[0092] These results indicate that the combination of decenoic acid and decenedioic acid, through its inhibitory effect on the expression levels of the wnt3 gene and bmp4 gene, is responsible for activating hair follicle stem cells, such as promoting the differentiation of hair follicle stem cells, promoting the proliferation of hair follicle stem cells, and inducing hair follicle stem cells in the telogen phase into the anagen phase.

[0093] The composition for activating hair follicle stem cells, the composition for inhibiting the expression of the wnt3 gene in hair follicle stem cells, and the composition for inhibiting the expression of the bmp4 gene in hair follicle stem cells according to one aspect of the present invention are naturally derived and contain active ingredients that are recognized as safe, and are capable of activating hair follicle stem cells through the inhibitory effect of the wnt3 gene and the bmp4 gene in hair follicle stem cells, and can be used in various forms such as foods and beverages, cosmetics, pharmaceuticals, and quasi-drugs. CROSS-REFERENCE TO RELATED APPLICATIONS

[0094] This application claims priority from Japanese Patent Application No. 2023-167245, filed September 28, 2023, the entire disclosure of which is incorporated herein by reference. In addition, the entire disclosures of all documents referenced in the detailed description of the invention of this application, including Patent Documents 1 and 2 and Non-Patent Documents 1 to 3, are incorporated herein by reference.

Claims

1. A composition for activating hair follicle stem cells comprising at least one first active ingredient selected from the group consisting of 10-hydroxy-2-decenoic acid, its derivatives, and salts thereof, and at least one second active ingredient selected from the group consisting of 2-decenedioic acid, its derivatives, and salts thereof.

2. A composition for inhibiting the expression of the wnt3 gene in hair follicle stem cells or a composition for inhibiting the expression of the bmp4 gene in hair follicle stem cells, comprising at least one first active ingredient selected from the group consisting of 10-hydroxy-2-decenoic acid and its derivatives, and salts thereof, and at least one second active ingredient selected from the group consisting of 2-decenedioic acid and its derivatives, and salts thereof.

3. The composition according to claim 1 or 2, which is a food or beverage, a cosmetic, a quasi-drug or a pharmaceutical.

4. A method for activating hair follicle stem cells, comprising applying to a subject at least one first active ingredient selected from the group consisting of 10-hydroxy-2-decenoic acid, its derivatives, and salts thereof, and at least one second active ingredient selected from the group consisting of 2-decenedioic acid, its derivatives, and salts thereof, to the subject, thereby activating the subject's hair follicle stem cells.

5. A method for suppressing expression of the wnt3 gene in hair follicle stem cells, comprising applying to a subject at least one first active ingredient selected from the group consisting of 10-hydroxy-2-decenoic acid, its derivatives, and salts thereof, and at least one second active ingredient selected from the group consisting of 2-decenedioic acid, its derivatives, and salts thereof, to the subject, thereby suppressing expression of the wnt3 gene in the subject's hair follicle stem cells.

6. A method for suppressing expression of the bmp4 gene in hair follicle stem cells, comprising applying to a subject at least one first active ingredient selected from the group consisting of 10-hydroxy-2-decenoic acid, its derivatives, and salts thereof, and at least one second active ingredient selected from the group consisting of 2-decenedioic acid, its derivatives, and salts thereof, to the subject, thereby suppressing expression of the bmp4 gene in the subject's hair follicle stem cells.

7. Use of at least one first active ingredient selected from the group consisting of 10-hydroxy-2-decenoic acid and its derivatives, and salts thereof, and at least one second active ingredient selected from the group consisting of 2-decenedioic acid and its derivatives, and salts thereof, to manufacture a composition for at least one effect selected from the group consisting of activation of hair follicle stem cells, inhibition of expression of wnt3 gene in hair follicle stem cells, and inhibition of expression of bmp4 gene in hair follicle stem cells.

8. The use according to claim 7, wherein the composition is a food or beverage, a cosmetic, a quasi-drug or a pharmaceutical.

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