JP6690220B2 - Agent for hair - Google Patents
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- JP6690220B2 JP6690220B2 JP2015244763A JP2015244763A JP6690220B2 JP 6690220 B2 JP6690220 B2 JP 6690220B2 JP 2015244763 A JP2015244763 A JP 2015244763A JP 2015244763 A JP2015244763 A JP 2015244763A JP 6690220 B2 JP6690220 B2 JP 6690220B2
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Description
本発明は、加齢やストレス等により生じる白髪の予防又は改善剤、bFGF(塩基性線維芽細胞増殖因子、basic Fibroblast Growth Factor、FGF-2)産生促進剤に関する。 The present invention relates to a preventive or ameliorating agent for gray hair caused by aging, stress, etc., a bFGF (basic fibroblast growth factor, FGF-2) production promoter.
体毛の色素は毛球部に存在する色素細胞により産生され、この色素を供給された毛母細胞が体毛を形成することにより、色素を持った体毛が発生する。体毛が生え変わる際に毛球部は消失し、それに伴って毛球部の色素細胞も消失する。新たな毛周期が始まり、新たな体毛が生じる際には、バルジ領域に存在する色素幹細胞より色素細胞が供給されることにより、再び色素を持った体毛が生じる。加齢や種々のストレスが原因となって、色素幹細胞が減少又は枯渇したり、色素細胞の供給過程に問題が生じることで、適切に色素細胞の供給が行なわれないと、色素を持たない白髪が発生する。
白髪の対処法として、一般に染毛剤が用いられているが、継続的な染毛が必要である煩わしさや、その刺激性からの髪へのダメージ、また接触皮膚炎が生じるなど、必ずしも十分とはいえない。
白髪の予防又は改善剤としては、色素細胞の色素合成に関わるチロシナーゼをはじめとする酵素を活性化する作用を指標として、数多くの物質が見出されている(特許文献1〜5、非特許文献1)。しかし、色素産生系を活性化しても、そもそも毛球部の色素細胞の数が不十分である場合等は、このような指標により見出された物質の効果はあまり期待できない。
The pigment of body hair is produced by pigment cells existing in the bulb portion, and the hair mother cells supplied with this pigment form body hair, so that the pigment-containing body hair is generated. When the hair grows, the bulb part disappears, and the pigment cells in the bulb part also disappear with it. When a new hair cycle begins and a new body hair is generated, pigment cells are supplied from the pigment stem cells existing in the bulge region, so that the pigmented body hair is generated again. Pigment stem cells are reduced or depleted due to aging and various stresses, and problems occur in the pigment cell supply process. Occurs.
Hair dyes are generally used as a coping method for gray hair, but the annoyance that requires continuous hair dyeing, damage to hair due to its irritative properties, contact dermatitis, etc. are not always sufficient. I can't say.
As a preventive or ameliorating agent for gray hair, many 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, Non-Patent Documents). 1). However, even if the pigment production 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.
白髪を予防するためには、色素幹細胞の減少を防いだり、毛母への移行を促進したり、減少した毛母の色素細胞を増加させることが重要であると考えられる。bFGFは色素細胞系譜の細胞全般に対して、細胞増殖作用を示す因子として知られることから(非特許文献2)、毛球部の色素細胞やバルジ領域の色素幹細胞の減少を食い止め、また数を増やし、白髪予防又は改善に対して有効であると考えられる。実際に、bFGFを頭皮に適用することで白髪予防又は改善効果を発揮することが明らかにされている(特許文献 6)。さらに毛乳頭細胞に作用し、bFGFをはじめとする因子の毛乳頭細胞からの発現を促す物質は、白髪を予防及び改善することが明らかにされている(特許文献7)。毛球部の色素細胞やバルジ領域の色素幹細胞に作用させるためには、毛包を構成する種々の細胞とインタラクションし、毛包の司令塔といわれる、毛乳頭細胞におけるbFGFの産生を促すことが重要である。 In order to prevent gray hair, it is considered important to prevent the decrease of pigment stem cells, promote the transfer to hair matrix, and increase the number of decreased pigment matrix of hair matrix. Since bFGF is known as a factor that exerts a cell proliferation effect on all cells of the pigment cell lineage (Non-patent Document 2), it suppresses the decrease of pigment cells in the bulb part and pigment stem cells in the bulge region and also It is considered to be effective in increasing or preventing gray hair. In fact, it has been clarified that applying bFGF to the scalp exerts a gray hair preventing or improving effect (Patent Document 6). Furthermore, it has been clarified that a substance that acts on dermal papilla cells and promotes expression of factors including bFGF from dermal papilla cells prevents and improves gray hair (Patent Document 7). In order to act on pigment cells in the hair bulb and pigment stem cells in the bulge region, it is important to interact with various cells that make up the hair follicle and promote bFGF production in hair papilla cells, which is called the control tower of the hair follicle. Is.
本発明の目的は、加齢やストレス等により生じる白髪を予防又は改善する手段を提供することである。本発明のもう一つの目的は、bFGFの産生を促す素材を提供することである。 An object of the present invention is to provide means for preventing or improving gray hair caused by aging, stress and the like. Another object of the present invention is to provide a material that promotes the production of bFGF.
そこで発明者らは鋭意検討した結果、多価アルコールを含む溶媒にて抽出したオウバクエキスが優れた白髪改善、または防止作用を有すると共に、その作用が非常に高いbFGF産生促進作用に起因することを見出し、本発明を完成するに至った。 Therefore, as a result of diligent studies, the inventors of the present invention have found that the psyllium extract extracted with a solvent containing a polyhydric alcohol has an excellent effect of improving or preventing gray hair, and that the effect is due to a very high bFGF production promoting effect. Heading out, the present invention has been completed.
すなわち、本発明は、
(1)多価アルコールを含む溶媒にて抽出したオウバクエキスを有効成分とする、白髪予防又は改善剤、
(2)さらに、発育毛物質を含有する、(1)に記載の白髪予防又は改善剤、
(3)皮膚外用である、(1)又は(2)に記載の白髪予防又は改善剤、
(4)多価アルコールを含む溶媒にて抽出したオウバクエキスを有効成分とする、bFGF産生促進剤、
(5)bFGF産生促進効果を有することを特徴とし、bFGFの産生を促進するために用いるものである旨の表示をした、(4)に記載のbFGF産生促進剤、
である。
That is, the present invention is
(1) A preventive or improver for gray hair, which contains, as an active ingredient, an oat extract extracted with a solvent containing polyhydric alcohol
(2) The agent for preventing or improving gray hair according to (1), which further contains a hair growth substance,
(3) The agent for preventing or improving gray hair according to (1) or (2), which is for external use on the skin.
(4) A bFGF production promoter, which contains, as an active ingredient, Oat extract extracted with a solvent containing polyhydric alcohol,
(5) The bFGF production-promoting agent according to (4), which has a bFGF production-promoting effect and is labeled as being used to promote the production of bFGF.
Is.
本発明の白髪予防又は改善剤は、毛乳頭細胞に対しbFGFの産生を促すことで、加齢やストレス等により生じる白髪の発生を予防し又は改善することができる。また、bFGFの産生を促進し得る新規な素材を提供することが出来る。 The agent for preventing or improving gray hair of the present invention can prevent or improve the occurrence of gray hair caused by aging, stress, etc. by promoting the production of bFGF in hair papilla cells. Further, it is possible to provide a novel material capable of promoting the production of bFGF.
本発明に用いるオウバクはムクロジ目ミカン科キハダ属キハダ(学名Phellodendron amurense)又はその他同属植物の周皮を除いた樹皮に由来する生薬である。
本発明に用いるオウバクエキスは、多価アルコール(1,3−ブチレングリコール、プロピレングリコール、ジプロピレングリコール、グリセリン)を含有する溶媒により抽出したものである。多価アルコールに加えて、水、低級脂肪族アルコール(メタノール、エタノール、イソプロピルアルコールなど)、低級脂肪族ケトン(アセトンなど)などを含有していても良く、このうち多価アルコールと水からなる混液で抽出することが最も好ましい。多価アルコールとしては、好ましくは1,3−ブチレングリコール、またはプロピレングリコールが挙げられるが、1,3−ブチレングリコールが最も好ましい。水と1,3−ブチレングリコールからなる溶媒で抽出する場合、溶媒中における1,3−ブチレングリコールの含有量は、30〜70体積%が好ましい。また、エキスの形態は特に制限されるものではなく、加熱処理、凍結乾燥あるいは減圧乾燥などの処理により、乾燥エキス末、エキス末、軟エキス、流エキスなどにすることができる。
The psyllium used in the present invention is a crude drug derived from the bark excluding the pericarp of the genus Phellidendron amurense of the citrus family Rutaceae (Scienceae) (scientific name Phellodendron amurense).
The psyllium extract used in the present invention is extracted with a solvent containing a polyhydric alcohol (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin). In addition to polyhydric alcohol, it may contain water, lower aliphatic alcohol (methanol, ethanol, isopropyl alcohol, etc.), lower aliphatic ketone (acetone, etc.), etc. Of these, a mixed liquid of polyhydric alcohol and water Most preferably, it is extracted with. The polyhydric alcohol is preferably 1,3-butylene glycol or propylene glycol, with 1,3-butylene glycol being most preferred. When extracting with a solvent composed 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 it can be made into a dry extract powder, an extract powder, a soft extract, a flow extract, etc. by a treatment such as heat treatment, freeze-drying or vacuum drying.
本発明の白髪予防又は改善剤は、化粧品、医薬部外品、医薬品又は飲食品等として提供することができる。その他、試薬として用いることも可能である。投与形態としては、特に限定されるものではないが、外用や内服が挙げられ、好ましくは頭皮を含む皮膚に適用する外用剤である。本発明を外用で適用する場合の剤形としては、例えば、ローション剤、液剤、クリーム剤、軟膏剤、ゲル剤、スプレー剤、シャンプー、コンディショナー、石鹸等が挙げられ、内服で適用する場合の剤形としては、錠剤、粉末剤、散剤、顆粒剤、液剤、カプセル剤、ドライシロップ剤、ゼリー剤、液状食品、半固形食品、固形食品等が挙げられる。これらは、公知の方法で製造することができる。製造に際しては、本発明の効果を損なわない範囲で、化粧品、医薬部外品、医薬品、飲食品又は試薬に含有可能な種々の添加物を配合することができる。 The agent for preventing or improving gray hair of the present invention can be provided as a cosmetic, a quasi drug, a drug, a food or drink, and the like. In addition, it can be used as a reagent. The dosage form is not particularly limited, but may be external use or internal use, and is preferably an external preparation applied to the skin including the scalp. Examples of dosage forms 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, and solid foods. These can be manufactured by a known method. At the time of production, various additives that can be contained in cosmetics, quasi-drugs, pharmaceuticals, foods and drinks or reagents can be blended within a range that does not impair the effects of the present invention.
さらに本発明の白髪予防又は改善剤は、センブリエキス、ニンジンエキス、トウガラシチンキ、ショウキョウチンキ、ビワ葉エキス、グリチルレチン酸、グリチルリチン酸ジカリウム、グリチルリチン酸モノアンモニウム、パントテン酸、パンテノール、ビタミンE及びその誘導体、ヒノキチオール、サリチル酸、ピロクトンオラミン、ミノキシジル、アデノシン、t-フラバノン、サイトプリン、ペンタデカン酸グリセリド、アラントイン、ニコチン酸アミドをはじめとした発育毛物質と組み合わせて使用することもできる。組み合わせることにより、毛の産生が早まり、早期に白髪予防又は改善効果を得ることができる。 Further, the preventive or improving agent for gray hair of the present invention is an assembly 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 a hair growth substance such as a derivative, hinokitiol, salicylic acid, piroctone olamine, minoxidil, adenosine, t-flavanone, cytopurine, pentadecanoic acid glyceride, allantoin or nicotinic acid amide. By combining them, the production of hair is accelerated, and the effect of preventing or improving gray hair can be obtained at an early stage.
本発明の多価アルコールを含む溶媒にて抽出したオウバクエキスの配合量は、化粧品、医薬部外品、医薬品、飲食品又は試薬で提供する場合、組成物全体に対して0.000001〜10質量%、好ましくは0.0001〜5質量%、より好ましくは0.001〜1質量%である。 The compounding amount of the psyllium extract extracted with the solvent containing the polyhydric alcohol of the present invention is 0.000001 to 10% by mass relative to the entire composition when provided as a cosmetic, a quasi drug, a drug, a food or drink or a reagent. The amount is preferably 0.0001 to 5% by mass, more preferably 0.001 to 1% by mass.
また、本発明のbFGF産生促進剤を含む製品(医薬品、医薬部外品、化粧品、飲食品、又は試薬)又はその説明書は、bFGF産生を促進するために用いられる旨の表示を付したものである。ここで、「製品またはその説明書に表示を付した」とは、製品の本体、容器、包装などに表示を付したこと、あるいは製品の情報を開示する説明書、添付文書、宣伝物、申請資料、その他の印刷物又は広告などに表示を付したことを意味する。また、これら表示においては、bFGF産生の促進に起因する疾患の予防又は治療のために用いられることに関する情報を含むことができる。 In addition, products containing the bFGF production promoter of the present invention (medicines, quasi drugs, cosmetics, foods and drinks, or reagents) or their instructions are labeled with an indication that they are used to promote bFGF production. Is. Here, "the product or its description is labeled" means that the product body, container, packaging, etc. is labeled, or a product information disclosure manual, package insert, advertising material, application This means that a display is attached to materials, other printed materials, advertisements, or the like. In addition, these indications can include information regarding use for prevention or treatment of diseases caused by promotion of bFGF production.
以下に実施例および試験例を挙げ、本発明をさらに具体的に説明するが、本発明は実施例に限定されない。 Hereinafter, the present invention will be described more specifically with reference to Examples and Test Examples, but the present invention is not limited to the Examples.
(試験例1)ヒト毛乳頭細胞に対するbFGF産生促進作用の評価
<試験方法>
ヒト毛乳頭細胞は2×104細胞/mLの密度で播種し、2日間、37℃、CO2 5%にセットしたインキュベーター内で予備培養した。培地には、12%FBS及び規定量のペニシリン・ストレプトマイシンを含むEarle’s MEMを用いた。予備培養後、PBSにて細胞表面を洗浄した後、無血清Earle’s MEMに交換した。さらに1日間培養した後、被験物質または対照物質を添加して24時間培養した。その後、培地を吸引除去し、ライセートバッファーを添加して細胞を溶解し、細胞溶解液を回収した。細胞溶解液より、RNeasy Mini Kit(キアゲン)を用いて添付のプロトコールに従いRNAを回収し、これを鋳型として、Prime Script RT Master mix(タカラバイオ)を用いた逆転写反応によりcDNAを合成した。合成したcDNAを用いてリアルタイムPCRシステム(Step One Plus、アプライドバイオシステムズ)により、GAPDH及びbFGFそれぞれのmRNAの発現量を測定し、bFGF発現量をGAPDH発現量により補正した。プライマー・プローブとしては、TaqMan Gene Expression Assays(GAPDH: Hs99999905_m1、bFGF: Hs00266645_m1、アプライドバイオシステムズ)を用いた。なお、被験物質としては、1,3−ブチレングリコール50体積%と水50体積%の混液により抽出したオウバクエキス(オウバクB)及びエタノール90体積%と水10体積%の混液により抽出したオウバクエキス(オウバクE)を用いた。
(Test Example 1) Evaluation of bFGF production promoting action on human hair papilla cells <Test method>
Human dermal papilla cells were seeded at a density of 2 × 10 4 cells / mL, and precultured for 2 days in an incubator set at 37 ° C. and CO 2 5%. Earle's MEM containing 12% FBS and a specified amount of penicillin-streptomycin was used as the medium. After pre-culturing, the cell surface was washed with PBS and then replaced with serum-free Earle's MEM. After further culturing for 1 day, a test substance or a control substance was added and culturing was continued for 24 hours. Then, the medium was removed by suction, lysate buffer was added to lyse the cells, and the cell lysate was collected. RNA was recovered from the cell lysate using the RNeasy Mini Kit (Qiagen) according to the attached protocol, and using this as a template, cDNA was synthesized by a reverse transcription reaction using Prime Script RT Master mix (Takara Bio). The mRNA expression levels of GAPDH and bFGF were measured by a real-time PCR system (Step One Plus, Applied Biosystems) using the synthesized cDNA, and the bFGF expression level was corrected by the GAPDH expression level. TaqMan Gene Expression Assays (GAPDH: Hs99999905_m1, bFGF: Hs00266645_m1, Applied Biosystems) were used as the primers and probes. In addition, as a test substance, an oat extract (Owaku B) extracted with a mixed solution of 50% by volume of 1,3-butylene glycol and 50% by volume of water and an extracted extract of Oataku (a mixture of 90% by volume of ethanol and 10% by volume of water). Oataku E) was used.
<試験結果>
図1は、オウバクのbFGF産生促進効果を評価した結果である。コントロール群のbFGF相対発現量を1としたときの各群のbFGF相対発現量を示す。1,3−ブチレングリコールと水の混液により抽出したオウバク抽出エキスは、3〜10μg/mLの濃度において、コントロール群と比較して有意に毛乳頭細胞におけるbFGFの発現量を上昇させた。プロスタグランジンF2α及びその誘導体には白髪予防又は改善作用があることが知られるが(特許文献8、非特許文献3、4)、オウバクエキスによるbFGF産生促進効果は、プロスタグランジンF2α 10μM(本試験系で最大の作用を示す濃度)と同等かそれ以上であった。一方、エタノールと水の混液により抽出したオウバクエキスは、コントロール群よりは高値を示したものの、1,3−ブチレングリコールと水の混液により抽出したオウバクエキスと比較するとその効果は非常に弱かった。
<Test results>
FIG. 1 shows the results of evaluating the bFGF production promoting effect of Oataku. The bFGF relative expression level of each group is shown when the bFGF relative expression level of the control group is 1. Oat extract extracted with a mixture of 1,3-butylene glycol and water at a concentration of 3 to 10 μg / mL significantly increased the expression level of bFGF in hair papilla cells compared with the control group. It is known that the prostaglandin F 2.alpha and its derivatives have white hair preventing or ameliorating action (Patent Document 8,
以上の結果から、オウバクの多価アルコール抽出エキスは毛乳頭細胞におけるbFGF産生を促進する効果を有することが明らかとなったので、本作用に基づき、オウバクの多価アルコール抽出エキスは白髪の予防又は改善効果を有することが示された。 From the above results, it was revealed that the polyhydric alcohol extract of Oatuba has the effect of promoting bFGF production in hair papilla cells, and therefore, based on this action, the polyhydric alcohol extract of Oataku prevents gray hair or It was shown to have an improving effect.
本発明のオウバクの多価アルコール抽出エキスはbFGF産生促進作用を有するため、加齢やストレス等により生じる白髪を予防及び改善用の化粧品、医薬部外品医薬品又は飲食品の分野に利用可能である。また、本発明のbFGF産生促進剤は、素材スクリーニング等を行なうに際し、陽性対照薬として用いることができる。 Since the extract of polyhydric alcohol of Oataku of the present invention has a bFGF production promoting action, it can be used in the fields of cosmetics, quasi-drugs, and foods and drinks for preventing and improving gray hair caused by aging, stress, etc. . In addition, the bFGF production promoter of the present invention can be used as a positive control drug in material screening and the like.
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