Dairy papilla cell activator and hair agent

Abstract

The purpose of the present invention is to provide a novel component capable of activating hair papilla cells, for example, for hair growth, hair growth, prevention of white hair, and the like. The hair papilla cell activator according to the present invention is characterized by containing at least one type of miR selected from the group consisting of miR-27a-3p, miR-140-5p, and miR-224-5p.

Description

Technical Field

[0001] This invention relates to hair papilla cell activators and hair care products. Background Technology

[0002] Thinning hair and gray hair are hair problems that can occur in both genders and at any age, and are generally believed to be caused by factors such as stress, aging, diet and lifestyle, sleep, and genetics. In recent years, various effective ingredients have been explored to address this problem, and compositions containing low-molecular-weight compounds have been reported (Patent Document 1). Existing technical documents Patent documents

[0003] Patent Document 1: Japanese Patent Application Publication No. 2023-050280 Summary of the Invention The problem that the invention aims to solve

[0004] Therefore, the object of the present invention is to provide a new ingredient that can activate hair papilla cells, thereby being used for purposes such as hair growth, hair development, and prevention of gray hair. Methods for solving problems

[0005] To achieve the above objectives, the dermal papilla cell activator of the present invention is characterized in that it comprises at least one miRNA selected from the group consisting of miR-27a-3p, miR-140-5p and miR-224-5p.

[0006] The hair product of the present invention is characterized in that it contains the hair papilla cell activator of the present invention. The effects of the invention

[0007] The inventors discovered that specific miRNAs can activate dermal papilla cells, thus establishing this invention. According to this invention, dermal papilla cells are activated, thereby enabling, for example, hair growth and prevention of gray hair. Attached Figure Description

[0008] Figure 1 A graph showing the expression levels of the VEGF and COL17A1 genes in dermal papilla cells in the presence of miRNA in Example 1. Detailed Implementation

[0009] [1] A dermal papilla cell activator, characterized in that it comprises at least one miRNA selected from the group consisting of miR-27a-3p, miR-140-5p and miR-224-5p. [2] A hair treatment, characterized in that it comprises a hair papilla cell activator according to [1]. [3] The hair treatment according to [2], wherein the hair treatment is used for hair growth and hair regrowth. [4] The hair treatment according to [2] or [3], wherein the hair treatment is used to prevent gray hair. [5] A method for activating dermal papilla cells, characterized in that it includes a step of administering at least one miRNA selected from the group consisting of miR-27a-3p, miR-140-5p and miR-224-5p to the scalp. [6] According to the method for activating hair papilla cells described in [5], the administration of the drug to the scalp is transdermal or subcutaneous. [7] A miRNA, wherein the miRNA is selected from at least one of the group consisting of miR-27a-3p, miR-140-5p and miR-224-5p, and the miRNA is used to activate dermal papilla cells. [8] A miRNA, wherein the miRNA is selected from at least one of the group consisting of miR-27a-3p, miR-140-5p and miR-224-5p, the miRNA being used to manufacture a dermal papilla activator.

[0010] Unless otherwise stated, the terms used in this specification may be used in the sense commonly understood in this technical field.

[0011] In this specification, "improving hair" refers to improving phenomena related to hair, such as hair growth, hair development, hair care, hair removal, and graying. Hair growth refers to, for example, promoting new hair growth; hair development refers to, for example, promoting hair growth; and hair care refers to, for example, inhibiting hair loss and protecting hair. "Improvement" can mean maintaining the current state, improving (becoming a better state, promoting), or preventing deterioration (preventing it from becoming a worse state). Preventing deterioration includes, for example, inhibiting deterioration and delaying deterioration. In this invention, improving hair also includes improving the scalp. In this invention, improvement also includes the meaning of treatment. Treatment can be any of the following meanings regarding the suppression, mitigation (improvement), relief, or cure of the symptoms being treated; in a broad sense, it can also include "prevention." "Prevention" includes, for example, inhibiting the onset of the symptoms being treated and delaying the onset of the symptoms. In this specification, for example, when "treatment" is defined in a narrow sense, "treatment" in this specification can be understood as prevention.

[0012] The present invention is illustrated by specific examples below, but the invention is not limited to these examples. Furthermore, the examples in each invention can be referenced mutually.

[0013] (1) Hair papilla cell activator As described above, the dermal papilla cell activator of the present invention is characterized by comprising at least one miRNA selected from the group consisting of miR-27a-3p, miR-140-5p, and miR-224-5p. In the present invention, miR-27a-3p, miR-140-5p, and miR-224-5p are referred to below as the miRNAs of the present invention.

[0014] In this invention, activating dermal papilla cells means, for example, significantly increasing the expression of at least one of the COL17A1 gene and the VEGF gene in dermal papilla cells compared to dermal papilla cells in the absence of the miRNA of this invention. The COL17A1 gene and the VEGF gene are known to be genes associated with hair growth, hair regrowth, and prevention of gray hair, respectively.

[0015] The gene name of COL17A1 (gene symbol) is type XVII collagen alpha 1. The gene symbol for VEGF is VEGFA, and its gene name is vascular endothelial growth factor A.

[0016] miR-27a-3p, miR-140-5p, and miR-224-5p are microRNAs (miRNAs). These three miRNAs are registered in the database (MiRBase: https: / / www.mirbase.org) with the following accession numbers. miR-27a-3p login ID MIMAT0000084 miR-140-5p login ID MIMAT0000431 miR-224-5p login ID MIMAT0000281

[0017] Since the sequence of the miRNA is publicly known, it can be synthesized, for example, by organic chemical methods or by genetic engineering methods. The miRNA may be chemically modified or unmodified.

[0018] In the dermal papilla cell activator of the present invention, the miRNA of the present invention is preferably a miRNA in a state not contained in biologically derived vesicles, and may also be referred to as free miRNA. Examples of the dermal papilla cell activators of the present invention include forms containing the miRNA of the present invention but not containing biologically derived vesicles.

[0019] The dermal papilla cell activator of the present invention comprises at least one miR selected from the group consisting of miR-27a-3p, miR-140-5p, and miR-224-5p as an active ingredient. The dermal papilla cell activator of the present invention may, for example, contain only the stated active ingredient, or it may contain the stated active ingredient and other additives.

[0020] The dermal papilla cell activator of the present invention may, for example, contain any one of the three miRNAs, or any combination of two (a combination of miR-27a-3p and miR-140-5p, a combination of miR-27a-3p and miR-224-5p, a combination of miR-140-5p and miR-224-5p), or may contain all three miRNAs. When two or three miRNAs are combined and used together, their ratio is not particularly limited.

[0021] The dermal papilla cell activator of the present invention may contain only the miR of the present invention as an active ingredient, or it may contain the miRNA of the present invention and other dermal papilla cell activating ingredients as active ingredients. The other dermal papilla cell activating ingredients are simply those that activate dermal papilla cells; for example, they may be known ingredients or ingredients that became known after the filing of this application.

[0022] The hair papilla cell activator of the present invention can be used, for example, to improve the hair of the subject organism. As a specific example, it can be used as the hair agent of the present invention.

[0023] The dermal papilla cell activator of the present invention is used, for example, by administering it to an organism. The organism may be a human or a non-human animal, and examples of non-human animals include mammals such as mice, rats, dogs, cats, monkeys, rabbits, cattle, goats, and camels.

[0024] The administration of the drug to the organism may be, for example, non-oral administration. Examples of non-oral administration include transdermal administration and subcutaneous administration. Examples of transdermal administration include application to the scalp, and examples of subcutaneous administration include injection into the subcutaneous tissue of the scalp.

[0025] The dosage of the dermal papilla activator of the present invention is not particularly limited, but it is preferably administered at a pharmaceutically effective amount. A pharmaceutically effective amount can be determined, for example, based on the route of administration, the type of hair-related improvement program, the presence and severity of symptoms related to the improvement program, age, and gender. Furthermore, the content of the miRNA of the present invention in the dermal papilla cell activator of the present invention is not particularly limited, but a pharmaceutically effective amount is preferred.

[0026] As a specific example, when the dermal papilla cell activator of the present invention is applied to the scalp, for example, the concentration of the miRNA of the present invention can be set to 0.1 to 100 nmol / L and applied to the entire scalp, for example, once a day. Furthermore, the daily application amount of the miRNA of the present invention, for example, is 0.1 to 100 nmol / L over the entire scalp, and the daily application frequency is, for example, once a day. Considering the hair cycle, the application interval is, for example, once a week, once a month, or once every three months. As described above, the content of the miRNA of the present invention in the dermal papilla cell activator of the present invention is not particularly limited, for example, it can be formulated in a manner that satisfies the exemplified dosage. Furthermore, the concentration of the miRNA of the present invention in the dermal papilla cell activator of the present invention is not particularly limited, for example, it can be a concentration that can be used directly, or a concentration that can be diluted before use.

[0027] As described above, the hair papilla cell activator of the present invention may, for example, contain the aforementioned active ingredient and other additives. Examples of additives include pharmaceutically acceptable ingredients. Specific examples include excipients and carriers (substrate). Examples of excipients and carriers include aqueous solvents such as water, physiological saline, and buffer solutions; oils such as soybean oil; petrolatum; alcohols such as glycerin; sugars such as maltose, glucose, and dextrin; sugar alcohols such as xylitol; phospholipids; and liposomes. In addition, examples of additives include binders, disintegrants, surfactants, emulsifiers, antioxidants, lubricants, humectants, thickeners, stabilizers, UV shielding agents, preservatives, vitamins, minerals, and colorants. Examples of additives include DDS such as liposome formulations; specific examples include phospholipid nanoparticles.

[0028] The dosage form of the hair papilla cell activator of the present invention is not particularly limited and can be appropriately selected according to the route of administration. Specific examples of the formulation include topical preparations (topical drugs) and injections. Topical preparations include transdermal preparations, and transdermal preparations are preferably applied to the scalp. The forms of the topical preparations include, for example, liquids, emulsions, gels, sols, ointments, etc.

[0029] The hair papilla cell activator of the present invention may be, for example, a pharmaceutical composition. The pharmaceutical composition may be, for example, a pharmaceutical product, a quasi-pharmaceutical, or a health supplement.

[0030] (2) Hair treatment As described above, the hair treatment of the present invention is characterized in that it comprises the dermal papilla cell activator of the present invention, and more specifically, it is characterized in that it comprises the miRNA of the present invention, that is, it comprises at least one miRNA selected from the group consisting of miR-27a-3p, miR-140-5p, and miR-224-5p. The hair treatment of the present invention may refer to the description in the dermal papilla cell activator of the present invention.

[0031] The hair growth regulator of the present invention, by containing the miRNA of the present invention, can increase the expression of genes related to hair growth, hair development, and prevention of gray hair, as described above. Therefore, the hair growth regulator of the present invention can, for example, be used to improve the condition of hair. The hair growth regulator of the present invention can, for example, improve hair-related symptoms, and therefore can also be called a hair improver or a hair symptom improver.

[0032] (3) Methods for activating hair papilla cells and methods for improving hair health The method for activating dermal papilla cells according to the present invention is characterized in that at least one miRNA selected from the group consisting of miR-27a-3p, miR-140-5p, and miR-224-5p is brought into contact with dermal papilla cells. In this embodiment, the miRNA of the present invention can be understood, for example, as the dermal papilla activator of the present invention.

[0033] The method for activating hair papilla cells of the present invention can be used, for example, in vitro or in vivo.

[0034] The method for activating dermal papilla cells according to the present invention, for example in vitro, includes a step of coexisting the dermal papilla cells with the miRNA of the present invention. This step preferably involves, for example, coexisting the dermal papilla cells with the miRNA of the present invention in a culture medium and then culturing them. The type of culture medium and the culture conditions are not particularly limited; for example, the general conditions for dermal papilla cells can be used.

[0035] Furthermore, the method for activating dermal papilla cells according to the present invention, for example in vivo, includes a drug delivery step of administering the miRNA of the present invention to an organism. This drug delivery step can be, for example, oral administration or non-oral administration, preferably non-oral administration. Examples of non-oral administration include transdermal administration and subcutaneous administration. Transdermal administration includes, for example, applying to the scalp, and subcutaneous administration includes, for example, injecting into the subcutaneous tissue of the scalp. Non-oral administration is preferably applied to the scalp. The conditions for administering the miRNA of the present invention are not particularly limited, and the conditions exemplified in the dermal papilla cell activator of the present invention can be referenced.

[0036] According to the present invention, the dermal papilla cells of an organism can be activated by administering the miRNA of the present invention to the organism. Specifically, the dermal papilla cells can be activated by significantly increasing the expression of at least one of the COL17A1 gene and the VEGF gene in the dermal papilla cells of an organism.

[0037] The hair improvement method of the present invention is characterized by a drug delivery step of administering the miRNA of the present invention to an organism. The miRNA of the present invention can be understood, for example, as the hair papilla activator or the hair treatment of the present invention.

[0038] There are no particular limitations on the conditions for administering the miRNA of the present invention, and the conditions exemplified in the hair papilla cell activator of the present invention can be referenced. The hair improvement method of the present invention can also be referred to as a hair care method, and hair care also includes scalp care.

[0039] According to the present invention, hair can be improved by administering the miRNA of the present invention to an organism. As described above, hair improvement includes, for example, hair growth, hair development, and improvement of gray hair. Specific examples include maintaining or improving hair growth, maintaining or improving hair development, preventing gray hair, and inhibiting the development of gray hair.

[0040] (4) Uses This invention relates to the application of at least one miR selected from the group consisting of miR-27a-3p, miR-140-5p, and miR-224-5p in activating dermal papilla cells. Additionally, this invention relates to the application of at least one miR selected from the group consisting of miR-27a-3p, miR-140-5p, and miR-224-5p in the manufacture of dermal papilla cell activators.

[0041] This invention relates to the application of at least one miR selected from the group consisting of miR-27a-3p, miR-140-5p, and miR-224-5p in hair improvement. Additionally, this invention relates to the application of at least one miR selected from the group consisting of miR-27a-3p, miR-140-5p, and miR-224-5p in the manufacture of hair growth products.

[0042] The present invention will now be described in detail through examples, but the present invention is not limited thereto. Example

[0043] [Example 1] Increased expression of the COL17A1 and VEGF genes was confirmed for miR-27a-3p, miR-140-5p, and miR-224-5p, which are miRNAs of the present invention.

[0044] (Reagents and conditions) Human Follicle Dermal Papilla Cells (HFDPC): Trade name 602-05A, Sigma-Aldrich Culture medium: Hair Follicle Dermal Papilla Cell Growth Medium, trade name 611-500, specialized culture medium, Sigma-Aldrich Collagen-coated flask: Trade name Collagen Coated T-75 Flask (125-75), Corning Incorporated Culture conditions: 37℃, 5% CO2, 95% Air

[0045] First, HFDPCs were pre-cultured in 6 mL of the aforementioned culture medium in a T-25 flask for 72 hours. Then, 6 mL of the pre-cultured medium was added to the flask containing 6 mL of fresh culture medium. After 18 hours of incubation, the miRNA was added to bring the final concentration in the medium to 10 nmol / L. To facilitate the introduction of the miRNA into the cells, an introduction reagent (trade name JetPEI (registered trademark), PPU Corporation) was added according to the instructions. Following the addition of the miRNA, the cells were cultured for another 72 hours, and then the HFDPCs were recovered (N=2).

[0046] Then, RNA was extracted from the recovered HEDPCs, and the expression levels of the COL17A1 gene (Assay ID: Hs00990076_g1) and the VEGF gene (Assay ID: Hs00900054_m1) were confirmed using TaqMan (registered trademark) gene expression analysis. It should be noted that, as a control (N=2), the expression levels of each gene were also confirmed for HEDPCs cultured in the same manner, except for the absence of miRs. Then, the expression levels of each gene in the control were set to 1, and the relative values ​​of the expression levels of each gene in cells cultured in the presence of each miR were calculated. These results are presented in… Figure 1 The chart.

[0047] Figure 1 This is a chart showing the relative expression levels of the COL17A1 and VEGF genes. The top chart shows the relative expression levels of the COL17A1 gene, and the bottom chart shows the relative expression levels of the VEGF gene. In each chart, the vertical axis represents the relative expression level. Figure 1As shown, for any given gene, increased expression was confirmed by culturing HEDPCs in the presence of each miR. miR-140-5p and miR-224-5p showed relatively high expression levels, with miR-224-5p showing a particularly significant increase in expression. These genes are known to be associated with hair growth, hair development, and prevention of gray hair. Therefore, it can be said that by promoting the expression of these genes through the miRs of the present invention, hair growth, hair development, and prevention of gray hair can be achieved.

[0048] The present invention has been described above with reference to the embodiments, but the present invention is not limited to the above embodiments. Within the scope of the present invention, various changes that can be understood by those skilled in the art can be made to the structure and details of the present invention.

[0049] This application claims priority based on Japanese Patent Application No. 2023-85976, filed on May 25, 2023, the entire contents of which are incorporated herein by reference. Industrial applicability

[0050] According to the present invention, hair papilla cells are activated, thereby enabling, for example, hair growth, hair development, and prevention of gray hair.

Claims

1. A hair papilla cell activator, characterized in that, It includes at least one miRNA selected from the group consisting of miR-27a-3p, miR-140-5p and miR-224-5p.

2. A hair growth tonic, characterized in that, It contains the hair papilla cell activator as described in claim 1.

3. The hair treatment according to claim 2, wherein, The hair growth product is used for hair growth and regrowth.

4. The hair treatment according to claim 2 or 3, wherein, The hair treatment is used to prevent gray hair.

5. A method for activating dermal papilla cells, characterized in that, The procedure includes administering at least one miRNA selected from the group consisting of miR-27a-3p, miR-140-5p, and miR-224-5p to the scalp.

6. The method for activating dermal papilla cells according to claim 5, wherein, Administering medication to the scalp is either transdermal or subcutaneous.

7. A miRNA, wherein, The miRNA is selected from at least one of the group consisting of miR-27a-3p, miR-140-5p and miR-224-5p, and the miRNA is used to activate dermal papilla cells.

8. A miRNA, wherein, The miRNA is selected from at least one of the group consisting of miR-27a-3p, miR-140-5p and miR-224-5p, and the miRNA is used to manufacture a dermal papilla activator.

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