JP2016121133A - Hair improving agent - Google Patents
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Images
Abstract
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 an agent for preventing or improving gray hair caused by aging, stress, etc., and an agent for promoting production of bFGF (basic fibroblast growth factor, FGF-2).
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。
The pigment of the hair is produced by pigment cells present in the hair bulb, and the hair matrix cells supplied with this pigment form body hair, so that the hair with the pigment is generated. When the hair changes, the hair bulb disappears, and the pigment cells in the hair bulb also disappear. When a new hair cycle starts and a new body hair is generated, a pigment cell is supplied from a pigment stem cell present in the bulge region, so that a hair with a pigment is generated again. Gray hair without pigment, if pigment cells are not properly supplied due to decrease or depletion of pigment stem cells due to aging and various stresses, or problems in the pigment cell supply process Will occur.
Hair dyes are generally used as a countermeasure for gray hair, but it is not always sufficient, such as the annoyance that requires continuous hair dyeing, damage to the hair from its irritation, and contact dermatitis. I can't say that.
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。 As an agent for preventing or improving gray hair, a large number of substances have been found by using an 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 part 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 in pigment stem cells, promote the transition to the hair matrix, and increase the pigment cells in the decreased hair matrix. Since bFGF is known as a factor that shows cell proliferation action on all cells of the pigment cell lineage (Non-patent Document 2), it stops the decrease of pigment cells in the hair bulb and bulge region and stems the number. It is considered effective for preventing or improving gray hair. In fact, it has been clarified that bFGF is applied to the scalp to exhibit the effect of preventing or improving white hair (Patent Document 6). Furthermore, substances that act on hair papilla cells and promote the expression of factors such as bFGF from hair papilla cells have been shown to prevent and improve gray hair (Patent Document 7). In order to act on pigment cells in the hair bulb and bulge pigment stem cells, it is important to interact with the various cells that make up the hair follicle and promote bFGF production in the dermal papilla cells, called the follicle control tower It 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、冬虫夏草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。 Thus, as a result of intensive studies, the present inventors have found that Cordyceps extract has an excellent white hair improvement or prevention action, and that the action is attributed to a very high bFGF production promoting action, and has led to the completion of the present invention. .
すなわち、本発明は、
（１）冬虫夏草エキスを有効成分とすることを特徴とする、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）冬虫夏草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、請求項４に記載のbFGF産生促進剤、
である。
That is, the present invention
(1) An agent for preventing or improving gray hair, characterized by comprising Cordyceps extract as an active ingredient,
(2) The white hair preventing or improving agent according to (1), further comprising a growth hair substance,
(3) The agent for preventing or improving white hair according to (1) or (2), wherein the agent is for external use on the skin.
(4) a bFGF production promoter containing Cordyceps extract as an active ingredient,
(5) The bFGF production promoter according to claim 4, characterized by having an effect of promoting bFGF production and displaying that it is used for promoting production of bFGF,
It 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 white hair according to the present invention can prevent or improve the generation of white hair caused by aging, stress, or the like by promoting the production of bFGF to the hair papilla cells. Moreover, a novel material that can promote the production of bFGF can be provided.
本発明に用いる冬虫夏草（学名Cordyceps sinensis）は、ボタンタケ目バッカクキン科冬虫夏草属に属するきのこの一種であり、その子実体とその宿主であるコウモリガ科Hepialidaeの昆虫、Hepialus armoricanus Oberthurなどの幼虫の複合体であってもよい。
本発明に用いる冬虫夏草エキスは、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）、多価アルコール（プロピレングリコール、１，３−ブチレングリコール、グリセリン、ジプロピレングリコールなど）、低級脂肪族ケトン（アセトンなど）などの溶媒により抽出したものを使用することができるが、エタノールと水の混液で抽出することが最も好ましい。水とエタノールからなる溶媒で抽出する場合、溶媒中におけるエタノールの含有量は、30〜90質量％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。
Cordyceps sinensis used in the present invention is a kind of mushroom belonging to the genus Cordycaceae, and is a complex of larvae such as its fruiting body and its host, Hepialidae, Hepialus armoricanus Oberthur. May be.
Cordyceps 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.), lower aliphatic ketones. Although what was extracted with solvents, such as (acetone etc.), can be used, it is most preferable to extract with the liquid mixture of ethanol and water. When extracting with the solvent which consists of water and ethanol, as for content of ethanol in a solvent, 30-90 mass% is preferable. 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 reduced pressure 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 cosmetics, quasi drugs, pharmaceuticals, foods and drinks, and the like. In addition, it can be used as a reagent.
Although it does not specifically limit as a dosage form, External application and internal use are mentioned, Preferably it is the external application applied to the skin containing a scalp.
Examples of the dosage form when the present invention is applied externally include, for example, lotions, liquids, creams, ointments, gels, sprays, shampoos, conditioners, soaps, and the like. 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 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 agent for preventing or improving gray hair of the present invention includes assembly extract, carrot extract, capsicum tincture, ginger tincture, loquat leaf extract, glycyrrhetinic acid, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, pantothenic acid, panthenol, vitamin E and its Derivatives, hinokitiol, salicylic acid, piroctone olamine, minoxidil, adenosine, t-flavanone, cytopurine, pentadecanoic acid glyceride, allantoin, and nicotinic acid amide can also be used in combination. By combining, hair production is accelerated, and the effect of preventing or improving gray hair can be obtained early.
本発明の冬虫夏草エキスの配合量は、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 amount of Cordyceps extract of the present invention is 0.000001 to 10% by mass, preferably 0.0001 to 5% by mass, more preferably, based on the whole composition when provided as a cosmetic, quasi-drug, pharmaceutical, food or drink, or reagent. Is 0.001-1 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 (pharmaceuticals, quasi-drugs, cosmetics, foods and drinks, or reagents) containing the bFGF production promoter of the present invention or instructions thereof are labeled with indication that they are used to promote bFGF production It is. Here, “labeled product or its instructions” means that the product body, container, packaging, etc. are labeled, or that the product information is disclosed, attached document, promotional material, application It means that a label is attached to a document, other printed matter or an advertisement. In addition, these displays can include information relating to use for the prevention or treatment of diseases caused by the 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。 EXAMPLES The present invention will be described more specifically with reference to examples and test examples. However, 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、エタノール70質量％と水30質量％の混液により抽出した冬虫夏草エキス（冬虫夏草E）を用いた。
(Test Example 1) Evaluation of bFGF production promoting action on human hair papilla cells <Test method>
Human hair papilla cells were seeded at a density of 2 × 10 4 cells / mL and pre-cultured in an incubator set at 37 ° C. and 5% CO 2 for 2 days. Earle's MEM containing 12% FBS and a prescribed amount of penicillin / streptomycin was used as the medium. After pre-culture, 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 cultured for 24 hours. Thereafter, the medium was removed by suction, lysate buffer was added to lyse cells, and the cell lysate was collected. RNA was collected from the cell lysate using RNeasy Mini Kit (Qiagen) according to the attached protocol, and cDNA was synthesized by reverse transcription using Prime Script RT Master mix (Takara Bio) using this as a template. Using the synthesized cDNA, mRNA expression levels of GAPDH and bFGF 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. TaqMan Gene Expression Assays (GAPDH: Hs99999905_m1, bFGF: Hs00266645_m1, Applied Biosystems) was used as a primer / probe. In addition, as a test substance, Cordyceps extract (Cycium Cordisus E) extracted with a mixed solution of 70% by mass of ethanol and 30% by mass of water was used.
＜試験結果＞
図１は、冬虫夏草の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。冬虫夏草エキスは、3μg/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）、冬虫夏草エキスによる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。
<Test results>
FIG. 1 shows the results of evaluating the bFGF production promoting effect of Cordyceps sinensis. The bFGF relative expression level of each group when the bFGF relative expression level of the control group is 1 is shown. Cordyceps extract significantly increased the expression level of bFGF in dermal papilla cells compared to the control group at a concentration of 3 μg / mL. Prostaglandin F 2α and its derivatives are known to have an effect of preventing or improving gray hair (Patent Document 8, Non-Patent Documents 3 and 4), but the bFGF production promoting effect by Cordyceps sinensis extract is prostaglandin F 2α 10 μM (Concentration showing maximum effect in this test system) or higher.
以上の結果から、冬虫夏草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、冬虫夏草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 clarified that Cordyceps extract has an effect of promoting bFGF production in hair papilla cells, and based on this action, Cordyceps extract has an effect of preventing or improving white hair.
本発明の冬虫夏草エキスは、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の予防又は改善用の化粧品、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。 The Cordyceps extract of the present invention has a bFGF production promoting action, and thus can be used in the fields of cosmetics, quasi-drugs, pharmaceuticals, and foods and drinks for preventing or improving gray hair caused by aging, stress, and the like. In addition, the bFGF production promoter of the present invention can be used as a positive control agent when performing material screening and the like.
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| JP6921284B1 (en) * | 2020-09-01 | 2021-08-18 | 株式会社 資生堂 | Adenosine-containing composition and a method for suppressing the precipitation of adenosine |
| WO2022050034A1 (en) * | 2020-09-01 | 2022-03-10 | 株式会社 資生堂 | Adenosine-containing composition and method for suppressing precipitation of adenosine |
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| JP6921284B1 (en) * | 2020-09-01 | 2021-08-18 | 株式会社 資生堂 | Adenosine-containing composition and a method for suppressing the precipitation of adenosine |
| JP6921348B1 (en) * | 2020-09-01 | 2021-08-18 | 株式会社 資生堂 | Adenosine-containing composition and a method for suppressing the precipitation of adenosine |
| WO2022050034A1 (en) * | 2020-09-01 | 2022-03-10 | 株式会社 資生堂 | Adenosine-containing composition and method for suppressing precipitation of adenosine |
| JP2022041622A (en) * | 2020-09-01 | 2022-03-11 | 株式会社 資生堂 | Adenosine-containing composition and method for suppressing precipitation of adenosine |
| JP2022041817A (en) * | 2020-09-01 | 2022-03-11 | 株式会社 資生堂 | Adenosine-containing composition and method for suppressing precipitation of adenosine |
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