JP5175437B2 - Hair restorer and hair restorer composition - Google Patents

Description

  The present invention relates to a hair restoration agent, a hair restoration composition, and a hair restoration method, and more specifically, a hair restoration agent comprising an inhibitor of apoptosis induction promoting protein as an active ingredient, and a hair restoration composition comprising the hair restoration agent. The present invention relates to a hair growth method using an inhibitor of a product, an apoptosis induction promoting protein.

  For humans, hair greatly affects the appearance and occupies a very important position in beauty. In addition, there is still no accurate treatment for alopecia, which is a source of deep concern for people with alopecia or its tendency. Although alopecia is congenital and acquired, there are many unclear points although many studies have been conducted on the cause and mechanism of alopecia areata. Therefore, the present condition is that a great number of hair-growth nourishing agents developed frantically are on the market.

  As the hair restoring agent, various hair restoration agents for hair restoration containing various chemicals have been provided so far. For example, a composition comprising a compound such as vitamin E, alloxazine, pyridine N-oxide, adenosine 3 ′, 5′-cyclic monophosphate (see, for example, Patent Documents 1 to 3), Yokuinin, Ginkgo biloba, Kashu, etc. The composition (for example, refer patent documents 4-6) formed by mix | blending herbal medicine extract of this is provided. In addition, vitamin E compounds and assembly extracts that have an effect of improving blood circulation, and compositions containing cysteine and methionine as amino acids as nutritional supplements and estradiol and ethinyl estradiol as female hormones are provided. ing. Furthermore, hair cosmetics for hair growth nourishing in which these active ingredients correspond to various causes of hair loss and are appropriately combined have been developed and used for the prevention and / or treatment of alopecia.

  Such conventional hair cosmetics for hair restoration are effective in improving dandruff and kayumi and preventing hair loss and promoting hair growth and hair growth. However, the effect varies greatly between individuals, and the effect is not sufficient. For this reason, there are still no products that can produce satisfactory results.

  On the other hand, recently, a hair loss inhibitor / hair nourishing agent using a caspase inhibitor that inhibits the apoptosis phenomenon has been proposed (see, for example, Patent Documents 7 and 8).

JP-A 64-56608 JP-A-1-261321 JP-A-2-204406 Japanese Patent Publication No. 1-13451 JP-A-2-48512 JP-A-2-48514 JP 2002-87937 A JP 2002-87938 A

  However, the hair loss suppressing and hair nourishing agents described in Patent Documents 7 and 8 contain a caspase inhibitor as an active ingredient, and this caspase inhibitor has an action of directly inhibiting the apoptosis phenomenon. This apoptotic phenomenon is essentially an important action for maintaining the homeostasis of the living body, and is not limited to the hair part, but the action extends to the entire living body. Therefore, the inhibition of the apoptotic phenomenon using a hair loss inhibitor / hair nourishing agent containing the caspase inhibitor suppresses the apoptotic phenomenon involved in the metabolic balance of the entire living body, and may cause side effects on the living body. There is.

  In addition, in the hair-growth nourishing agents provided so far, extracts such as the above-mentioned various compounds and herbal medicines are applied. Moreover, even if it has a certain effect, there is a drawback that continuous use is difficult, such as skin irritation and side effects.

  The present invention has been made in view of the above, and is excellent in hair-growth hair-growth effects, has sufficient safety to withstand long-term use, and promotes more effective hair-growth hair growth in mammals. It is an object of the present invention to provide a highly safe hair restoration agent, a hair restoration composition containing the hair restoration agent, a hair restoration effect, and a highly safe hair restoration method.

  In order to solve the above-mentioned problems, the present inventors have searched for a drug that is effective in preventing hair loss, hair growth, and the like and has excellent safety. Specifically, in order to elucidate the cause of alopecia, first, gene expression comparison was performed in the hair papilla cells of the hair loss site of the hair loss person and the corresponding site of the non-hair loss person. That is, the gene expressed in each cell of the hair loss site of the hair loss person and the corresponding site of the non-hair loss person was comprehensively analyzed using DNA array analysis. As a result, a group of factors with increased gene expression and a group of factors with decreased gene expression were compared between the hair papilla cells at the hair loss site of the hairless person and the hair papilla cells at the corresponding site of the non-haired person. I found out that it exists. Furthermore, as a result of studying these factor groups, genes that are particularly expressed in hair loss have genes that encode proteins involved in promoting apoptosis induction, and conversely, genes that have decreased expression have apoptosis. It was revealed that many proteins encode proteins involved in suppression of induction.

  It is known that the apoptosis-related protein newly associated with alopecia thus found is increased or decreased in male pattern alopecia caused by the action of male hormones. Therefore, the present inventors can return the hair to a normal state by controlling the action of these proteins and returning it to a normal state. We thought that it would be possible to provide a hair restorer with no side effects.

  Based on this idea, the present inventors focused on a protein whose expression is increased in male pattern baldness caused by the action of the male hormone, and searched for a drug that inhibits the action of the protein. It was. As a result, a drug that effectively suppresses the action of the protein has been found.

  That is, the hair growth method of the present invention promotes hair growth by suppressing the action of an apoptosis-related protein whose expression is increased by the action of male hormones in at least the part of the mammal in which hair growth is desired. It is characterized by that.

  More specifically, hair growth is promoted by suppressing the activity of a protein involved in promoting apoptosis induction (hereinafter also referred to as “apoptosis induction promoting protein”) with its inhibitor.

  That is, the hair growth agent of the present invention is characterized by containing an inhibitor of apoptosis induction promoting protein as an active ingredient.

  The inhibitor is not particularly limited as long as it does not cause a problem in safety. Examples of such inhibitory substances include natural product extracts and synthetic compounds.

  Examples of the inhibitor include Chinhi, Kusetsu-sho, Syakuka, Astragalus, Phytocollage (derived from pea (soybean)), Shioyogi (Shuyoboku), Tachibana ( Preferable is at least one extract selected from the group consisting of Kita-raku) and Guangxi.

  In addition, as the inhibitor, at least one extract selected from the group consisting of Asaku, Echonia, Darus, Okakusa, Tsutsuregusa, Tochaka, Calophyllus, Okinawa Mozuku, Ginnan, Dragusa, Fruceraria, Willow Moku, Mozuku is also preferable.

  Moreover, the composition for hair growth nourishment of this invention contains the said hair growth agent. Preferred examples of the hair-restoring hair-restoring composition include hair-restoring hair-growth pharmaceuticals and hair-restoring hair-care agents.

  Further, the hair growth composition of the present invention further comprises at least one selected from the group consisting of odd chain fatty acids having carbon chain lengths of 11, 13, 15, and 17, thereby further improving hair growth effects. Demonstrate.

  The hair growth method of the present invention is characterized by using an inhibitor of the apoptosis induction promoting protein.

  In addition, the "hair growth nourishing agent" as used in the field of this invention has the effect | action which accelerates | stimulates hair growth and hair restoration, and it added to the target composition, and the composition for hair restoration hair growth which provided the effect of promoting hair growth hair restoration was added. Means an agent for preparing The effect of promoting hair growth can be obtained by applying the hair growth composition containing the hair growth agent of the present invention mainly to the scalp.

The hair growth agent according to the present invention has an excellent hair growth promotion effect and has safety sufficient to withstand long-term use, and hair growth including hair cosmetics and pharmaceuticals for hair growth. Suitable as an active ingredient for hair nourishing compositions.
Moreover, since the hair growth method of the present invention has an excellent hair growth promotion effect and high safety, it can be carried out on a daily basis.

Hereinafter, embodiments of the present invention will be described.
The hair growth agent of the present invention is characterized by containing an inhibitor of apoptosis induction promoting protein as an active ingredient.

  The inhibitor of the apoptosis induction promoting protein is not particularly limited as long as it does not cause a problem in safety. Examples of such inhibitory substances include natural product extracts and synthetic compounds.

  Examples of the inhibitor include Chinhi, Kusetsu-sho, Syakuka, Astragalus, Phytocollage (derived from pea (soybean)), Shioyogi (Shuyoboku), Tachibana ( Preferable is at least one extract selected from the group consisting of Kita-raku) and Guangxi. These are plant-derived extracts. Among these plant-derived extracts, a chinhi extract is particularly preferable. In addition, the said Astragalus refers to the thing of the above-ground part.

  In addition, as the inhibitor, at least one extract selected from the group consisting of Asaku, Echonia, Darus, Okakusa, Tsutsuregusa, Tochaka, Calophyllus, Okinawa Mozuku, Ginnan, Dragusa, Fruceraria, Willow Moku, Mozuku is also preferable. These are plant or seaweed extracts. Among these plant or seaweed extracts, extracts of asaku, echronia, dallus, and okasa are particularly preferred.

  The plant or seaweed used for the extraction of the plant or seaweed extract is not particularly limited in its use, but from the viewpoint of exerting its effectiveness, asaku is made of wood, echronia, dulls, okusa, tsutsuregusa, tochaka, It is preferable to use the whole plant or seaweed for Calophyllus, Okinawa Mozuku, Ginnan Sou, Dragusa, Fruceraria, Willow Mok, and Mozuku. The “wood” means the woody part of the stem of a woody plant.

  As the plant-derived material and plant extract, commercially available products or those obtained by known extraction methods can be used. Examples of the solvent used in the extraction method (hereinafter referred to as “extraction solvent”) include water; alcohols such as methanol, ethanol, propanol, and butanol; and polyhydric alcohols such as propylene glycol and butylene glycol. Can be used alone or as a mixed solvent of two or more.

  Various conditions in the extraction method are not particularly limited, but the ratio of the extraction raw material to the extraction solvent is usually in a range of about 1: 2 to 1:50 extraction raw material: extraction solvent = 1: 50 by mass ratio. preferable. The extraction temperature is preferably in the range of 5 to 80 ° C., and is preferably performed by immersing or stirring in the extraction solvent for 1 hour to 1 week. The extraction pH is not particularly limited as long as it is not extremely acidic or alkaline.

  When the extraction solvent is a non-toxic solvent such as water, ethanol, water / ethanol (hydrous ethanol) or the like, the extract may be used as it is as a hair growth agent or as a diluent. Further, the extract may be a concentrated extract, which may be formed into a dry powder by freeze-drying or the like, or may be prepared as a paste. When other solvents are used, it is desirable to dilute the dried portion with a non-toxic solvent after distilling off the solvent.

  By adding the hair-restoring agent of the present invention to a predetermined target composition, a hair-restoring composition that imparts a hair-restoring effect to the target composition can be obtained.

  When the hair growth agent of the present invention is added to a predetermined target composition, the blending amount of the extract in the target composition varies depending on the product form and frequency of use, and cannot be specified unconditionally. On the other hand, the extract is preferably 0.001 to 1.0% by mass (hereinafter abbreviated as%), particularly 0.01 to 1.0% as described above. If the amount is less than 0.001%, a sufficient effect cannot be expected, and if it exceeds 1.0%, the effect may reach a peak or a problem may occur in the stability of the preparation. .

  The hair growth composition of the present invention preferably further contains at least one fatty acid selected from the group consisting of odd chain fatty acids having carbon chain lengths of 11, 13, 15, and 17. It is because a synergistic hair growth effect can be obtained by including the fatty acid. The concentration of these fatty acids is preferably 0.0005 to 50%, particularly preferably 0.25 to 25%. This is because if the amount is less than 0.0005%, a sufficient effect cannot be expected, and if it exceeds 50%, the effect may reach a peak or a problem may occur in the stability of the preparation.

  The hair restoring composition for hair growth of the present invention may further contain an existing hair restoring component. Examples of existing hair nurturing ingredients include chemistry such as PDG (pentadecanoic acid glyceride), Coleus extract described in JP-A No. 09-157136, Gentianana extract described in JP-A No. 10-45539, Matsukasa extract, royal jelly extract, and kumazasa extract. Mention may be made of substances and extracts. Among these, PDG and Coleus extract are preferable from the viewpoint of hair restoration effect.

  As the chemical substances and extracts exemplified as the existing hair growth component, commercially available products or those obtained by known methods can be used. In particular, the extracts can be obtained by extraction of plant components. In this case, the solvent used for extraction includes water; alcohols such as methanol, ethanol, propanol, and butanol; polyhydric alcohols such as propylene glycol and butylene glycol, and the like. These may be used alone or in combination of two or more. Can be used as a mixture. The extraction method may be carried out in accordance with a method such as the extraction method of an ordinary plant extract, and may be used after performing treatment such as deodorization and decolorization by a known method if necessary. Commercially available extracts can also be used.

  Moreover, arbitrary components other than the said active ingredient can be mix | blended with the composition for hair growth nourishment of this invention according to the intended purpose. Examples of such components include purified water, ethanol, nonionic surfactants, saccharide surfactants and other surfactants, celluloses, fats and oils, ester oils, polymer resins, colorants, Examples include fragrances, ultraviolet absorbers, vitamins, hormones, vasodilators, amino acids, anti-inflammatory agents, skin function enhancers, medicinal ingredients such as keratolytic agents, and the like.

  Examples of the celluloses include hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, and the like.

  Examples of the surfactant include sorbitan fatty acid esters (sorbitan monolaurate, sorbitan monooleate, etc.), polyoxyethylene hydrogenated castor oil, polyoxyethylene hydrogenated castor oil mono- or isostearate, glycerin fatty acid ester, polyglycerin. Fatty acid ester (monomyristic acid decaglycerol, monomyristic acid pentaglycerol), etc. are mentioned.

  Examples of the fats and oils include polyhydric alcohol fatty acid esters (such as glycerin tri-2-ethylhexanoate and trimethylolpropanoic acid triisostearate), safflower oil, evening primrose oil, jojoba oil, and the like.

  Examples of the ester oil include unsaturated fatty acid alkyl esters (such as ethyl oleate and isopropyl linoleate) methyl myristate and isopropyl myristate.

  Examples of the amino acids include methionine, serine, glycine, cystine and the like.

  Examples of the keratolytic agent include salicylic acid and resorcin.

  Examples of the polymer resin include amphoteric, cationic, anionic and nonionic polymers.

  Examples of the ultraviolet absorber include octyl methoxycinnamate (Neoheliopan AV), oxybenzone, urocanic acid, and the like.

  When other proteins are blended in the hair growth composition of the present invention, they can be blended in any amount.

  The field of application of the hair-restoring composition of the present invention includes various external preparations (including preparations used for animals) in general. Specifically, capsules, powders, granules, solids, liquids, gels, ointments, or foams (1) pharmaceuticals, (2) quasi drugs, (3) topical or systemic (4) Medicinal and / or cosmetic preparations applied to the scalp and hair (eg shampoos, rinses, treatments, permanent liquids, hair dyes, hair preparations, hair styling agents, hair growth / Hair nourishing etc.).

  Examples of the hair-growth nourishing composition of the present invention include hair-growth hair-growth hair cosmetics and hair-growth hair-growth medicinal products containing the hair-growth nourishing agent as an active ingredient. In the hair cosmetic for hair growth and the pharmaceutical for hair growth, a known medicinal component can be appropriately blended as needed within a range not impairing the effects of the present invention. As known medicinal components, for example, antibacterial agents, anti-inflammatory agents, humectants and the like can be blended.

  The hair cosmetic for hair growth and the pharmaceutical for hair growth of the present invention can be used by external application in the form of a uniform solution, lotion, gel, etc. according to a conventional method. Moreover, the hair cosmetic for nurturing hair of the present invention can take the form of an aerosol, in which case, in addition to the above components, lower alcohols such as n-propyl alcohol or isopropyl alcohol: butane, propane, isobutane, Combustible gas such as liquefied petroleum gas and dimethyl ether: compressed gas such as nitrogen gas, oxygen gas, carbon dioxide gas and nitrous oxide gas can be contained.

  Hereinafter, the present invention will be described in more detail based on examples. In addition, this invention is not limited to the following Example.

<Example 1-2 and Reference Example 1-19>
The plant-derived materials and plants shown in the following "Table 1" as test samples were extracted with 70% ethanol and seaweed with water, and the obtained extract was dried to obtain a solid extract. This solid was dissolved in ethanol to a concentration of 100 mg / ml. The extract thus prepared was added to keratinocytes previously cultured at 20,000 cells / well so that the final concentration was 100 μg / ml. At the same time, apoptosis induction promoting protein (Neurotrophin-4, hereinafter abbreviated as “NT-4”) was added to the well so that the final concentration was 1 ng / ml. After 24 hours, the apoptosis induction rate was measured using the TUNEL method. The apoptosis induction rate was determined by staining the cells causing apoptosis using a TUNEL staining kit “TACS _™ 2 TdT DAB” (manufactured by TREVIGEN) and determining the ratio thereof.

  Table 1 below shows the results of the apoptosis induction suppression test. As shown in “Table 1”, the extract was found to suppress apoptosis induction of keratinocytes. In addition, it was revealed that apoptosis induction is particularly excellent in scab, asaku, echronia, dallus, and geek. Therefore, it was recognized that the said extract is an active ingredient of a hair growth nourishing agent.

<Comparative Example 1>
As Comparative Example 1, ethanol was added to keratinocytes previously cultured at 20,000 cells / well so that the final concentration was 0.1%, and at the same time, NT-4 was adjusted to a final concentration of 1 ng / ml. Added. It was determined apoptosis induction rate in the same manner as in Example 1-2 and Reference Example 1-19. As a result, the action of the apoptosis induction promoting protein was not suppressed, and apoptosis was induced.

◎： ＮＴ−４のみ添加の場合に比べ８０％以上抑制
○： ＮＴ−４のみ添加の場合に比べ５０〜８０％抑制
×： ＮＴ−４のみ添加の場合と変わらない

◎: Suppressed by 80% or more compared to the case of adding only NT-4 ○: Suppressed by 50 to 80% compared to the case of adding only NT-4 ×: Same as the case of adding only NT-4

<Examples 3 to 4 and Reference Examples 20 to 21 >
In the same manner as in Examples 1 and 2 and Reference Examples 1 to 19 , solids of the extract of husk, kushi kushi, liquor and asaku were obtained. Next, hair growth agent samples were prepared with the compositions shown in “Table 2”. Using this hair-restoring agent sample, a hair-restoration test in mice was conducted as follows.

First, almost the entire back of the C3H mouse was shaved with an electric clipper. As a group of 7 animals, the hair-restoring agent compounded as shown in the following “Table 2” was applied to the shaved part at 100 μl per day for 5 consecutive days, and after that, it was not applied for 2 days. Performed once. The growth of the coat at the application site was evaluated by visual observation. For the hair restorer sample of Reference Example 20 , use a scab extract, for the hair restorer sample of Example 3 , use the kushi koji extract, for the hair restorer sample of Reference Example 21 , use the liquor flower extract, Asaku extract was used for the hair restorer sample of Example 4 .

As shown in the following "Table 2", the hair-growth-promoting effect was recognized in the example hair-growth agent sample containing the extract. In particular, an excellent hair-growth-promoting effect was observed with scab and Asaku. Therefore, it was recognized that the hair restorer samples of Examples 3 to 4 are excellent hair restorer compositions.

<Comparative example 2>
As Comparative Example 2, 0.1% ethanol was used instead of the hair restorer sample. The test results of the hair growth effect of the mice after 15 days are shown in “Table 2” below. As a result, as shown in “Table 2”, hair growth was only observed in some parts of the cut hair.

5： 全面に毛が生える
4： ほぼ全面に毛が生える
3： 半面程度に毛が生える
2： ところどころ発毛が認められるが半面に毛が生えるまでには至らない
1： ほとんど毛が生えない

5: Hair grows on the entire surface
4: Hair grows almost on the entire surface
3: Hair grows on one side
2: Some hair growth is observed in some places, but it does not lead to hair growing on one side
1: Almost no hair

  As described above, the hair-growth nourishing agent of the present invention has an excellent hair-growth nourishing effect, and has safety sufficient to withstand long-term use. The hair growth composition of the present invention has an excellent hair growth effect and is suitable as a hair cosmetic for hair growth and a pharmaceutical product for hair growth having safety sufficient to withstand long-term use. It is.

Claims (6)

A hair restoration agent comprising a neurotrophin-4 (NT-4) -dependent apoptosis inhibitor as an active ingredient, wherein the inhibitor is an extract of Kusetsu-shobu A hair growth nourishing agent characterized by. A hair restorer comprising a neurotrophin -4 (NT-4) -dependent apoptosis inhibitor as an active ingredient, wherein the inhibitor is an extract of Asakut.   A hair growth nourishing composition comprising the hair growth nourishing agent according to claim 1 or 2.   The hair growth composition according to claim 3, further comprising at least one fatty acid selected from the group consisting of odd chain fatty acids having carbon chain lengths of 11, 13, 15, and 17.   5. The hair growth composition according to claim 4, wherein the composition is a hair growth medicine.   5. The hair-growth composition for hair growth according to claim 4, which is a hair cosmetic for hair growth.