JP2023028376A - White hair inhibitor - Google Patents

Abstract

To provide an agent for preventing or improving white hair, an agent for inhibiting DNA damage or promoting its repair, or an agent for promoting the production of SCF.SOLUTION: The present invention provides an agent for preventing or improving white hair, an agent for inhibiting cellular DNA damage or promoting its repair, or an agent for promoting the production of SCF, comprising at least one selected from the group consisting of raspberry extract, Gardenia fruit extract, and perilla extract as an active ingredient.SELECTED DRAWING: Figure 2

Description

TECHNICAL FIELD The present invention relates to an agent for preventing or improving gray hair, an agent for suppressing or promoting repair of DNA damage, and an agent for promoting SCF (Stem cell factor, KITL, KIT ligand, Steel factor, Mast cell growth factor) production.

Pigment in body hair is produced by pigment cells present in the hair bulb of the hair follicle, which is the tissue of the hair. Body hair with it occurs. When the body hair regrows, the region existing below the bulge region of the hair follicle such as the old hair bulb disappears, and the pigment cells in the hair bulb disappear accordingly. When a new hair cycle begins and new body hair is produced, pigment cells are supplied from the melanocyte stem cells present in the bulge region of the hair follicle to produce pigmented body hair again. Due to aging and various stresses, melanocyte stem cells are reduced or depleted, and problems occur in the supply process of melanocytes. If melanocytes are not properly supplied, gray hair without pigment occurs.

In addition, hair follicle keratinocytes such as hair follicle epithelial stem cells (hereinafter referred to as hair follicle stem cells) are present adjacent to melanocyte stem cells in the bulge region. Hair follicle stem cells supply hair follicle epithelial cells, such as hair matrix cells, when body hair regrows, and these cells form new hair follicle tissue. Furthermore, hair follicle stem cells may have a function of forming a microenvironment for maintaining melanocyte stem cells existing adjacently (hereinafter referred to as a niche function) in addition to the function of reconstructing the epithelial cells of the hair follicle. (Non-Patent Document 1, Patent Document 1). Hair follicle stem cells maintain melanocyte stem cells by controlling the maintenance and activation of melanocyte stem cells by TGFβ and WNT signals. From this, it is thought that the decrease in melanocyte stem cells is caused by the loss of the niche function of hair follicle stem cells as a result of accumulated damage to hair follicle stem cells due to aging and various stresses (Non-Patent Document 2). .

It has also been found that mice in which SCF is forcedly expressed in keratinocytes, including hair follicles, show resistance to gray hair development stress. Therefore, enhancing SCF expression in epithelial cells leads to maintenance of melanocyte stem cells and melanocytes, and is useful for prevention and improvement of gray hair (Non-Patent Document 3).

SCF is also known as a factor that promotes the proliferation and differentiation of various cells such as hematopoietic cells, mast cells and pigment cells, and plays an important role in hematopoiesis, spermatogenesis and melanogenesis. In the skin, keratinocytes and fibroblasts are produced, and by promoting pigment cell proliferation and melanin production, it contributes to the maintenance and improvement of healthy skin color. In hair follicles, hair follicle epithelial cells, their stem cells, and dermal papilla cells are produced, and by improving the growth and viability of pigment cells and their stem cells, hair, eyelashes, and other body hair colors are maintained and improved. It is expected to prevent and improve gray hair.

JP 2009-035514 A

Tanimura S et al (2011) Cell Stem Cell., 6(2):130-40. Aoki H et al (2013) J Invest Dermatol., 133(9):2143-51. Aoki H et al (2011) J Invest Dermatol. 131(9):1906-15.

An object of the present invention is to provide an agent for preventing or improving gray hair, an agent for suppressing DNA damage or promoting repair, and an agent for promoting SCF production.

As a result of intensive studies, the inventors found that SCF is involved in suppression of DNA damage or promotion of repair because it reduces the number of γH2AX Forsythocytes, which is an indicator of DNA damage, in experiments using epidermal pigment cells. . Furthermore, since it has been reported that SCF is involved in the reduction of gray hair development, the present inventors have found that a component that promotes SCF production can be used to prevent and improve gray hair. As a result of material screening, it was found that the raspberry extract, the garden extract and the perilla extract have an SCF production-promoting effect.

That is, the present invention
(1) an agent for preventing or improving gray hair, containing as an active ingredient at least one selected from the group consisting of raspberry extract, gardenia extract, and perilla extract;
(2) an agent for suppressing DNA damage or promoting repair of cells, containing as an active ingredient at least one selected from the group consisting of raspberry extract, sansis extract, and perilla extract;
(3) The agent for suppressing DNA damage or promoting repair according to claim 2, wherein the cells are pigment cells;
(4) an SCF production promoter containing as an active ingredient at least one selected from the group consisting of a raspberry extract, a garden extract, and a perilla extract;
is.

The agent for preventing or improving gray hair, the agent for suppressing or repairing DNA damage, and the agent for promoting SCF production of the present invention prevent the occurrence of gray hair caused by aging, stress, etc. by promoting SCF production in hair follicle keratinocytes. or can be improved. In addition, by promoting the production of SCF, it is possible to suppress DNA damage or promote repair of pigment cells. Also, it is possible to provide a novel material capable of promoting the production of SCF.

1 is a graph showing the DNA damage-inhibiting or repair-promoting action of SCF in Test Example 1. FIG. 4 is a graph showing the SCF expression level in Test Example 2. FIG.

The raspberry extract used in the present invention is an extract obtained from the fruit of Raspberries of the genus Rubus (scientific name: Rubus idaeus) belonging to the family Rosaceae. Moreover, the gardenia extract used in the present invention is an extract obtained from the fruit of Gardenia jasminoides (scientific name: Gardenia jasminoides) belonging to the family Rubiaceae of the Gentian order. The perilla extract is an extract obtained from leaves or leaves and branch tips of Perilla frutescens (scientific name: Perilla frutescens) or other related plants Labiatae.

The raspberry extract and perilla extract used in the present invention are extracted with a solvent such as water, polyhydric alcohol (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.) or a mixture thereof. In addition to polyhydric alcohols, it may contain lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), lower aliphatic ketones (acetone, etc.), etc., and the raspberry extract is extracted with polyhydric alcohols. is most preferred. The perilla extract is most preferably extracted with a mixture of polyhydric alcohol and water. The polyhydric alcohol preferably includes 1,3-butylene glycol or propylene glycol, with 1,3-butylene glycol being most preferred. When extracting with a solvent consisting of water and 1,3-butylene glycol, the content of 1,3-butylene glycol in the solvent is preferably 30 to 70% by volume.

The honeycomb extract used in the present invention is diluted with a solvent such as water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (propylene glycol, 1,3-butylene glycol, glycerin, dipropylene glycol, etc.). Although an extracted product can be used, it is preferable to extract with a mixture of ethanol and water or a mixture of polyhydric alcohol and water, and most preferably a mixture of 1,3-butylene glycol and water. When extracting with a solvent consisting of water and 1,3-butylene glycol, the content of 1,3-butylene glycol in the solvent is preferably 30 to 70% by volume.

Also, the form of the extract is not particularly limited, and can be made into dry extract powder, extract powder, soft extract, liquid extract, etc. by heat treatment, freeze-drying or vacuum drying. Commercially available raspberry extracts include Rubus extract liquid BG100 (manufactured by Maruzen Pharmaceutical Co., Ltd.) and Falcorex Rubus B (manufactured by Ichimaru Falcos). Gardenia B (manufactured by Ichimaru Pharcos), gardenia extract (manufactured by Koei Kogyo), and perilla extract commercially available include perilla extract BG (manufactured by Maruzen Pharmaceutical), Falcolex perilla HB (manufactured by Ichimaru Farcos), and perilla extract. (manufactured by Koei Kogyo Co., Ltd.) and the like.

The pigment in the present invention is melanin, and the pigment cell in the present invention is a pigment, that is, a cell capable of producing melanin, such as a melanocyte or a melanoma cell, regardless of the biological species of origin. Also included are immature pigment cells, chromoblasts (melanoblasts) and melanocyte stem cells.

The agent for preventing or improving gray hair of the present invention can be provided as cosmetics, quasi-drugs, pharmaceuticals, food and drink, and the like. In addition, it can also be used as a reagent.

Furthermore, the gray hair preventive or improving agent of the present invention includes jersey extract, carrot extract, capsicum tincture, ginger tincture, loquat leaf extract, glycyrrhetinic acid, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, pantothenic acid, panthenol, vitamin E and its It can also be used in combination with hair growth substances such as derivatives, hinokitiol, salicylic acid, piroctone olamine, minoxidil, adenosine, t-flavanone, cytopurine, pentadecanoic acid glyceride, allantoin, nicotinic acid amide. By combining them, hair growth is accelerated, and an effect of preventing or improving gray hair can be obtained at an early stage.

The DNA damage inhibitor or repair promoter of the present invention protects cells from factors that induce DNA damage, such as radiation, ultraviolet rays, aging, and oxidative stress, and suppresses DNA damage. Although it is not limited whether it is a tissue cell, for example, it suppresses DNA damage of epidermal tissue cells such as hair follicle stem cells and pigment cells, and cells of the cornea and conjunctiva. Factors that induce cellular DNA damage include, but are not limited to, radiation such as X-rays, α-rays, β-rays, γ-rays, and neutron beams, ultraviolet irradiation, aging, and oxidative stress. The DNA damage inhibitor of the present invention exerts an effect on DNA damage induced by aging, irradiation or ultraviolet irradiation.

According to the SCF production promoting agent of the present invention, through excellent SCF production promoting action, for example, melanin production action based on the proliferation activation of pigment cells, prevention and / or improvement of gray hair and vitiligo, or healthy skin Can be used for skin color purposes. In addition, SCF is a cytokine that plays a central role in hematopoiesis. Since it promotes differentiation, it can be used for the prevention and/or treatment of these hematopoiesis-related conditions and diseases, such as neutropenia and agranulocytosis. In addition to these uses, it can be used for all uses that are significant in exhibiting the SCF production-promoting action.

The dosage form is not particularly limited, but includes external use and internal use, preferably external use applied to the skin including the scalp. Dosage forms for external application of the present invention include, for example, lotions, liquids, creams, ointments, gels, sprays, shampoos, conditioners, soaps, etc., and agents for internal application. Forms include tablets, powders, powders, granules, liquids, capsules, dry syrups, jellies, liquid foods, semi-solid foods, solid foods and the like.

These can be produced by known methods. During production, various additives that can be contained in cosmetics, quasi-drugs, pharmaceuticals, food and drink, or reagents can be blended within limits that do not impair the effects of the present invention.

The amount of the raspberry extract or sansis extract or perilla extract of the present invention is 0.000001 to 10 mass with respect to the entire composition when provided as cosmetics, quasi-drugs, pharmaceuticals, food and drink, or reagents. %, preferably 0.0001 to 5 mass %, more preferably 0.001 to 1 mass %.

EXAMPLES The present invention will be described in more detail with reference to examples and test examples below, but the present invention is not limited to the examples.

(Test Example 1) Evaluation of DNA damage inhibition or repair promotion effect of SCF on normal human epidermal pigment cells <Test method>
Normal human epidermal pigment cells (Kurashiki Spinning Co., Ltd.) were seeded on a culture plate and cultured in an incubator set at 37°C and 5% CO2 until subconfluent. DermaLife M Comp kit (Kurashiki Boseki) was used as the medium. After culturing, the medium was replaced with the same medium supplemented with 1/10 times the specified amount of StiMel 8 Life Factor, recombinant human SCF protein was added, and the cells were cultured for 3 days, and then irradiated with X-rays (4 Gy). After 5 hours, γH2AX, which is an index of DNA damage, was stained by immunofluorescence, and the number of γH2AX Forsy's per cell was counted. Recombinant human SCF protein dissolved in 0.1% BSA/PBS was used as the test substance at the final concentration shown in FIG. A 0.1% BSA/PBS addition group was used as a control.

<Test results>
FIG. 1 shows the evaluation results of the DNA damage suppression or repair promotion action. SCF significantly reduced the number of γH2AX Forsy's. Therefore, it was shown that SCF and substances having SCF production-promoting action are effective in suppressing DNA damage or promoting repair of cells.

(Test Example 2) Evaluation of SCF production promotion effect on human hair follicle keratinocytes <Test method>
Human hair follicle keratinocytes (Cosmo Bio) were seeded on culture plates and cultured in an incubator set at 37° C. and 5% CO ₂ . Humedia-KG2 (Kurashiki Boseki) was used as the medium. On the day after seeding, the medium was replaced, the test substance was added, and the cells were cultured for 2 days. After that, a lysate buffer was added to lyse the cells, and the cell lysate was collected. RNA was recovered from the cell lysate using RNeasy Mini Kit (Qiagen) according to the attached protocol, and using this as a template, cDNA was synthesized by reverse transcription using Prime Script RT Master mix (Takara Bio). From the synthesized cDNA, the expression levels of RPLP2 and SCF mRNA were measured using a real-time PCR system (Step One Plus, Thermo Fisher Scientific) (SYBR Green method), and the SCF expression level was corrected by the RPLP2 expression level. . The following primers were used. RPLP2: HA067804 (Takara Bio), SCF: HA122146 (Takara Bio). The test substances were a raspberry extract extracted with 100% by volume of 1,3-butylene glycol, and a sansis extract and perilla extract extracted with a mixture of 50% by volume of 1,3-butylene glycol and 50% by volume of water. Used at the final concentrations indicated. The control group was obtained by omitting the extracts from the group added with the raspberry extract, the gardenia extract and the perilla extract (all other conditions such as the solvent were the same as those for the raspberry extract, the gardenia extract and the perilla extract).

<Test results>
FIG. 2 shows the results of evaluation of the SCF production-enhancing effects of a raspberry extract, a garden extract and a perilla extract. The SCF relative expression level of each group is shown when the expression level of the control group to which no test substance is added is set to 1. The raspberry extract, the Japanese shiso extract and the perilla extract significantly increased the amount of SCF expression. Therefore, it was shown that the raspberry extract, the garden extract and the perilla extract are effective in preventing and improving gray hair.

The agent for preventing or improving gray hair, the agent for suppressing or promoting repair of DNA damage, and the agent for promoting SCF production of the present invention have an effect of promoting SCF production. are available in the field of

Claims (4)

An agent for preventing or improving gray hair, comprising at least one selected from the group consisting of a raspberry extract, a garden extract and a perilla extract as an active ingredient. An agent for suppressing DNA damage or promoting repair of cells, containing as an active ingredient at least one selected from the group consisting of a raspberry extract, a garden extract, and a perilla extract. 3. The agent for suppressing DNA damage or promoting repair according to claim 2, wherein the cells are pigment cells. An SCF production promoter comprising, as an active ingredient, at least one selected from the group consisting of a raspberry extract, a garden extract, and a perilla extract.

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