JP6945273B2 - Hair agent - Google Patents

Description

The present invention relates to a bFGF (basic Fibroblast Growth Factor, FGF-2) production promoter, which is a preventive or ameliorating agent for gray hair caused by aging, stress, or the like.

The pigment of the body hair is produced by the pigment cells existing in the hair bulb, and the hair matrix cells supplied with this pigment form the body hair to generate the pigmented body hair. When the hair grows, the hair bulb disappears, and the pigment cells in the hair bulb disappear accordingly. When a new hair cycle begins and new hair is produced, pigment cells are supplied from pigment stem cells existing in the bulge region, so that pigmented hair is produced again. Due to aging and various stresses, pigment stem cells are reduced or depleted, or problems occur in the pigment cell supply process, and if pigment cells are not properly supplied, pigment-free white hair Occurs.
Hair dyes are generally used as a treatment for gray hair, but it is not always sufficient because of the inconvenience of requiring continuous hair dyeing, damage to the hair due to its irritation, and contact dermatitis. I can't say.

As a preventive or ameliorating agent for white hair, a large number of substances have been found with the action of activating enzymes such as tyrosinase involved in pigment synthesis of pigment cells as an index (Patent Documents 1 to 5 and Non-Patent Documents). 1). However, even if the pigment-producing system is activated, if the number of pigment cells in the hair bulb is insufficient in the first place, the effect of the substance found by such an index cannot be expected so much.

In order to prevent gray hair, it is considered important to prevent the decrease of pigment stem cells, promote the transfer to the hair matrix, and increase the pigment cells of the decreased hair matrix. Since bFGF is known as a factor showing cell proliferation on all cells of the pigment cell lineage (Non-Patent Document 2), it stops the decrease of pigment cells in the hair bulb and pigment stem cells in the bulge region, and increases the number. It is considered to be effective for proliferation and prevention or improvement of gray hair. In fact, it has been clarified that applying bFGF to the scalp exerts an effect of preventing or improving white hair (Patent Document 6). Furthermore, it has been clarified that a substance that acts on dermal papilla cells and promotes the expression of factors such as bFGF from dermal papilla cells prevents and improves white hair (Patent Document 7). In order to act on the pigment cells in the hair bulb and the pigment stem cells in the bulge region, it is important to interact with various cells that make up the hair follicle and promote the production of bFGF in the hair papilla cells, which is called the control tower of the hair follicle. Is.

Patent 4433241 JP 2001-131032 Patent 4921732 JP 2011-157317 JP 2002-47130 Japanese Patent Application Laid-Open No. 5-43424 Japanese Patent Application Laid-Open No. 2003-171240 JP 2010-126475

Hideaki Matsuda et al., "Anti-Aging Series 1 Practice of White Hair, Hair Loss, and Hair Growth" NTS, July 4, 2005, p.37-48 Hirobe T et al., Life cycle of human melanocytes is regulated by endothelin-1 and stem cell factor in synergy with cyclic AMP and basic fibroblast growth factor, J Dermatol Sci, 57 (2), 123-131, (2010) Sasaki S et al., Influence of prostaglandin F2alpha and its analogues on hair regrowth and follicular melanogenesis in a murine model, Exp Dermatol, 14 (5), 323-328, (2005) Bellandi S et al., Repigmentation of hair after latanoprost therapy, J Eur Acad Dermatol Teleel, 25 (12), 1485-1487, (2010)

An object of the present invention is to provide a means for preventing or improving white hair caused by aging, stress, or the like. Another object of the present invention is to provide a material that promotes the production of bFGF.

Therefore, as a result of diligent studies, the inventors have found that Hibamata has an excellent whitening hair improving or preventing action and that the action is due to a very high bFGF production promoting action, and has completed the present invention. We also found that this effect was enhanced when combined with Phellodendron amur.

That is, the present invention
(1) A white hair preventive or improving agent containing Hibamata or its extract as an active ingredient.
(2) The white hair preventive or ameliorating agent according to (1), which further contains Phellodendron amurensis or an extract thereof.
(3) The white hair preventive or ameliorating agent according to (1) or (2), which further contains a hair growth substance.
(4) The white hair preventive or ameliorating agent according to (1) to (3), which is for external use on the skin.
(5) A bFGF production promoter containing Hibamata or an extract thereof as an active ingredient.
(6) The bFGF production promoter according to (5), which further contains Phellodendron amurensis or an extract thereof.
(7) The bFGF production promoter according to (6), which is characterized by having a bFGF production promoting effect and is labeled to be used for promoting bFGF production.
Is.

The white hair preventive or ameliorating agent of the present invention can prevent or improve the development of white hair caused by aging, stress, etc. by promoting the production of bFGF in the dermal papilla cells. In addition, it is possible to provide a novel material capable of promoting the production of bFGF.

FIG. 1 is a graph showing the relative expression level of bFGF in Test Example 1. In the figure, Hibamata B is a Hibamata extract obtained from a mixture of 1,3-butylene glycol and water, and Hibamata E: a Hibamata extract obtained from a mixed solution of ethanol and water. FIG. 2 is a graph showing the relative expression level of bFGF in Test Example 1. In the figure, Phellodendron amur B is a Phellodendron amur extract obtained by mixing 1,3-butylene glycol and water.

The rockweed (scientific name: Fucus vesiculosus) used in the present invention is a brown alga belonging to the genus Fucales of the order Fucales. The Phellodendron amurense used in the present invention is a crude drug derived from the bark of Phellodendron amurense (scientific name: Phellodendron amurense) of the family Rutaceae of the order Sapindales or other plants of the same genus. Hibamata and Oubaku are used in the form of crude drug powder and crude drug extract. The crude drug powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The hibamata extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (propylene glycol, 1,3-butylene glycol, glycerin, dipropylene glycol, etc.), and lower aliphatic ketones. A mixture extracted with a solvent such as (acetone, etc.) can be used, but it is preferable to extract with a mixed solution of ethanol and water or a mixed solution of polyhydric alcohol and water, and a mixed solution of 1,3-butylene glycol and water. Is the most preferable. 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 Oubaku extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (propylene glycol, 1,3-butylene glycol, glycerin, dipropylene glycol, etc.), and lower aliphatic ketones. Those extracted with a solvent such as (acetone or the like) can be used, but those extracted with a solvent containing a polyhydric alcohol (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin) are preferable. In addition to polyhydric alcohol, water, lower fatty alcohol (methanol, ethanol, isopropyl alcohol, etc.), lower aliphatic ketone (acetone, etc.), etc. may be contained, of which a mixed solution consisting of polyhydric alcohol and water. It is most preferable to extract with. The polyhydric alcohol preferably includes 1,3-butylene glycol or propylene glycol, but 1,3-butylene glycol is most preferable. 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 form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying.

The whitening hair preventing or improving agent of the present invention can be provided as cosmetics, quasi-drugs, pharmaceuticals, foods and drinks, and the like. In addition, it can also be used as a reagent. The administration form is not particularly limited, and examples thereof include external use and internal use, and is preferably external use applied to the skin including the scalp. Examples of the dosage form when the present invention is applied externally include lotions, liquids, creams, ointments, gels, sprays, shampoos, conditioners, soaps, etc. Examples of the form 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. In the production, various additives that can be contained in cosmetics, quasi-drugs, pharmaceuticals, foods and drinks, or reagents can be blended as long as the effects of the present invention are not impaired.

Further, the white hair preventive or ameliorating agent of the present invention includes sembly extract, carrot extract, capsicum tincture, ginger tincture, biwa leaf extract, glycyrrhetinic acid, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, pantothenic acid, panthenol, vitamin E and the like. It can also be used in combination with hair growth substances such as derivatives, hinokithiol, salicylic acid, pyrocton olamine, minoxidil, adenosine, t-flabanone, cytopurine, pentadecanoic acid glyceride, allantin, and nicotinic acid amide. By combining them, hair production is accelerated, and the effect of preventing or improving white hair can be obtained at an early stage.

The blending amount of Hibamata or its extract, or Oubaku or its extract of the present invention is 0.000001 to 10% by mass, preferably 0.000001 to 10% by mass, based on the entire composition when provided in cosmetics, quasi-drugs, pharmaceuticals, foods and drinks or reagents. It is 0.0001 to 5% by mass, more preferably 0.001 to 1% by mass.

In addition, the product (pharmaceutical product, quasi-drug, cosmetics, food or drink, or reagent) containing the bFGF production promoter of the present invention or its instruction manual is labeled as being used for promoting bFGF production. Is. Here, "indication is attached to the product or its instruction manual" means that the indication is attached to the main body, container, packaging, etc. of the product, or the instruction manual, package insert, advertisement, application that discloses the information of the product. It means that a display is attached to materials, other printed matter, advertisements, etc. In addition, these indications can include information regarding being used for the prevention or treatment of diseases and symptoms caused by the promotion of bFGF production.

Hereinafter, the present invention will be described in more detail with reference to Examples and Test Examples, but the present invention is not limited to the Examples.

(Test Example 1) Evaluation of bFGF production promoting action on human dermal papilla cells <Test method>
Human hair papilla cells were seeded at a density of 2 × 10 ⁴ cells / mL, 2 days, 37 ° C., were pre-cultured in an incubator set at CO ₂ 5%. As the medium, Earle's MEM containing 12% FBS and a specified amount of penicillin / streptomycin was used. After preculture, the cell surface was washed with PBS and then replaced with serum-free Earle's MEM. After culturing for another 1 day, a test substance or a control substance was added and the cells were cultured for 24 hours. Then, the medium was aspirated and removed, lysate buffer was added to lyse the cells, and the cytolytic solution was collected. RNA was recovered from the cell lysate according to the attached protocol using RNeasy Mini Kit (Qiagen), and cDNA was synthesized by reverse transcription reaction using Prime Script RT Master mix (Takara Bio) using this as a template. Using the synthesized cDNA, the expression levels of GAPDH and bFGF mRNA were measured by a real-time PCR system (Step One Plus, Applied Biosystems), and the bFGF expression level was corrected by the GAPDH expression level. As the primer probe, TaqMan Gene Expression Assays (GAPDH: Hs99999905_m1, bFGF: Hs00266645_m1, Applied Biosystems) were used. The test substances were Hibamata extract (Hibamata B) extracted with a mixture of 50% by volume of 1,3-butylene glycol and 50% by volume of water, and Hibamata extract (Hibamata extract) extracted with a mixture of 10% by volume of ethanol and 90% by volume of water. Hibamata E) and Oubaku extract (Oubaku B) extracted by a mixed solution of 50% by volume of 1,3-butylene glycol and 50% by volume of water were used.

<Test results>
FIG. 1 shows the results of evaluating the bFGF production promoting effect of Hibamata alone. The bFGF relative expression level of each group is shown when the bFGF relative expression level of the control group is 1. Hibamata extract (Hibamata B) extracted with a mixture of 1,3-butylene glycol and water significantly increased the expression level of bFGF in hair papilla cells at a concentration of 3 to 10 μg / mL as compared with the control group. .. It is known that prostaglandin F _2α and its derivatives have a whitening prevention or ameliorating effect (Patent Document 8, Non-Patent Documents 3 and 4), but the bFGF production promoting effect of Hibamata extract is prostaglandin F _2α 10 μM. It exceeded (concentration showing the maximum effect in this test system). The same effect was observed in the Hibamata extract (Hibamata E) extracted with a mixed solution of ethanol and water. However, its action was weaker than that of the rockweed extract extracted by a mixed solution of 1,3-butylene glycol and water.
From the above results, it was clarified that the rockweed has an effect of promoting the production of bFGF in the dermal papilla cells, and it was shown that the rockweed has a preventive or ameliorating effect on white hair based on this action.
FIG. 2 shows the results of evaluating the bFGF production promoting effect when the Hibamata extract and the Oubaku extract are combined. Both Hibamata and Oubaku show a bFGF production promoting effect alone, but by combining these, the action was synergistically promoted.
Therefore, it was shown that the combination of Hibamata and Oubaku enhances the effect of preventing or improving white hair.

Since the Hibamata or its extract of the present invention has a bFGF production promoting action, it can be used in the fields of cosmetics, quasi-drugs, pharmaceuticals or foods and drinks for preventing or improving white hair caused by aging, stress, etc. .. In addition, the bFGF production promoter of the present invention can also be used as a positive control agent when performing material screening and the like.

Claims (7)

A white hair preventive or improving agent containing Hibamata or an extract thereof as an active ingredient. The white hair preventive or ameliorating agent according to claim 1, further containing Phellodendron amurensis or an extract thereof. The white hair preventive or ameliorating agent according to claim 1 or 2, further comprising a hair growth substance. The white hair preventive or ameliorating agent according to claims 1 to 3, which is for external use on the skin. A bFGF production promoter containing Hibamata or an extract thereof as an active ingredient. The bFGF production promoter according to claim 5, further containing Phellodendron amurensis or an extract thereof. The bFGF production promoter according to claim 5 or 6, which is characterized by having a bFGF production promoting effect and is labeled to be used for promoting the production of bFGF.

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