JP2016183137A - Hair growth or hair restoration promoter - Google Patents

Hair growth or hair restoration promoter Download PDF

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JP2016183137A
JP2016183137A JP2015065407A JP2015065407A JP2016183137A JP 2016183137 A JP2016183137 A JP 2016183137A JP 2015065407 A JP2015065407 A JP 2015065407A JP 2015065407 A JP2015065407 A JP 2015065407A JP 2016183137 A JP2016183137 A JP 2016183137A
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JP6655296B2 (en
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隆司 藤田
Takashi Fujita
隆司 藤田
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Ritsumeikan Trust
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Abstract

PROBLEM TO BE SOLVED: To provide a hair growth or hair restoration promoter.SOLUTION: The present invention provides a hair growth or hair restoration promoter that comprises extract derived from at least one plant selected from the group consisting of Forsythia, Pouzolzia, Barringtonia, Anogeissus, Ailanthus and Indigofera.SELECTED DRAWING: None

Description

本発明は、植物から収得した発毛促進活性および育毛促進活性を有する抽出物に関する。より詳しくは、レンギョウ属(Forsythia)、オオバヒメマオ属(Pouzolzia)、サガリバナ属(Barringtonia)、アノゲイスス属(Anogeissus)、ニワウルシ属(Ailanthus)およびコマツナギ属(Indigofera)からなる群から選択される属に属する少なくとも1つの植物由来の抽出物を有効成分として含有する、発毛または育毛促進剤に関する。   The present invention relates to an extract having hair growth promoting activity and hair growth promoting activity obtained from a plant. More particularly, at least belonging to the genus selected from the group consisting of Forsythia, Pouzolzia, Barringtonia, Anogeissus, Ailanthus and Indigofera. The present invention relates to a hair growth or hair growth promoter containing an extract derived from one plant as an active ingredient.

毛髪は、成長期、退行期及び休止期からなる周期的な毛周期に従って成長及び脱落を繰り返している。この毛周期のうち、休止期から成長期にかけての新たな毛包が形成されるステージが、発毛に最も重要であると考えられており、このステージにおける毛包上皮系細胞の増殖・分化に重要な役割を果たしているのが、毛乳頭細胞であると考えられている。毛乳頭細胞は、毛根近傍にある外毛根鞘細胞とマトリックス細胞とからなる毛包上皮系細胞の内側にあって、基底膜に包まれている毛根の根幹部分に位置する細胞であり、毛包上皮系細胞に働きかけてその増殖を促進する等、毛包上皮系細胞の増殖・分化及び毛髪の形成において重要な役割を担っている。   Hair repeats growth and loss according to a periodic hair cycle consisting of a growth phase, a regression phase, and a resting phase. Of these hair cycles, the stage at which new hair follicles are formed from the resting stage to the growing stage is considered to be the most important for hair growth. In this stage, the proliferation and differentiation of hair follicle epithelial cells are considered. It is believed that the dermal papilla cells play an important role. The dermal papilla cell is a cell located inside the hair follicle epithelial cell composed of outer root sheath cells and matrix cells in the vicinity of the hair root, and located in the root portion of the hair root wrapped in the basement membrane. It plays an important role in the growth and differentiation of hair follicle epithelial cells and the formation of hair, such as by promoting the proliferation of epithelial cells.

毛周期が停滞又は短縮した状態は脱毛症と呼ばれ、医療現場で日常的に見られる脱毛症は、加齢に伴う壮年性脱毛症や精神的ストレスに伴う円形脱毛症のほか、癌や内分泌異常などの疾病に伴うものや抗癌剤等の薬剤による脱毛などが知られている。脱毛は、患者の容姿に大きく影響を及ぼすものであることから、根本的な治療法や予防法の開発が望まれている。   A state in which the hair cycle is stagnant or shortened is called alopecia, and alopecia that is routinely seen in the medical field includes not only alopecia areata associated with aging and alopecia areata associated with mental stress, but also cancer and endocrinology. Hair loss caused by diseases such as abnormalities and drugs such as anticancer agents is known. Since hair loss greatly affects the patient's appearance, the development of a fundamental treatment and prevention method is desired.

脱毛症に対する治療又は予防に用いられる薬剤としてはフィナステリド又はミノキシジルが市販されているが、フィナステリドに関しては性機能障害、ミノキシジルに関してはかゆみや炎症といった副作用が生じることが知られている。   Finasteride or minoxidil is commercially available as a drug used for the treatment or prevention of alopecia, but it is known that finasteride has side effects such as sexual dysfunction, and minoxidil has itching and inflammation.

一方、民間療法や伝統医学(例えば、漢方医学)で古くから用いられてきた植物抽出エキスは、副作用等の恐れが少なく、長期間、安全に服用、又は摂取可能であるという長所を有している。このため、医薬品や食料品の分野において植物由来の有効成分の探索研究が国内外において盛んに行われており、脱毛症の予防または治療に用いることができる植物抽出エキスもまた、探索の対象となっている。例えば、鎮咳作用、利尿作用などが知られる桑白皮の抽出物は、育毛活性があることが報告されている(特許文献1)。   On the other hand, plant extracts that have been used for a long time in folk remedies and traditional medicine (eg, Kampo medicine) have the advantage that they can be taken or ingested safely for a long period of time with little risk of side effects. Yes. For this reason, research on active ingredients derived from plants has been actively conducted in Japan and overseas in the field of pharmaceuticals and foodstuffs, and plant extracts that can be used for the prevention or treatment of alopecia are also subject to search. It has become. For example, it has been reported that an extract of mulberry skin known to have an antitussive action, a diuretic action, and the like has hair growth activity (Patent Document 1).

このような現状において、より効果的かつ副作用のない発毛または育毛促進剤が望まれている。   Under such circumstances, hair growth or hair growth promoters that are more effective and have no side effects are desired.

特開2014-218479号公報JP 2014-218479 A

本発明は、植物由来の抽出物を有効成分として含有する発毛または育毛促進剤を提供することを目的とする。   An object of this invention is to provide the hair growth or the hair growth promoter which contains the plant-derived extract as an active ingredient.

本発明者は、レンギョウ属(Forsythia)、オオバヒメマオ属(Pouzolzia)、サガリバナ属(Barringtonia)、アノゲイスス属(Anogeissus)、ニワウルシ属(Ailanthus)、コマツナギ属(Indigofera)に属する植物由来の抽出物が、毛周期の休止期から成長期への移行期間を短縮する効果および毛の伸長速度を高める効果があることを初めて見出し、該抽出物を含有する発毛または育毛促進剤を完成した。   The inventor of the present invention is an extract derived from a plant belonging to the genus Forsythia, Pouzolzia, Barringtonia, Anogeissus, Ailanthus, Indigofera. The inventors discovered for the first time that they had the effect of shortening the transition period from the rest period of the cycle to the growth period and the effect of increasing the hair elongation rate, and completed the hair growth or hair growth promoter containing the extract.

すなわち、本発明は、
[1]レンギョウ属(Forsythia)、オオバヒメマオ属(Pouzolzia)、サガリバナ属(Barringtonia)、アノゲイスス属(Anogeissus)、ニワウルシ属(Ailanthus)およびコマツナギ属(Indigofera)からなる群から選択される属に属する少なくとも1つの植物由来の抽出物を含む、発毛または育毛促進剤;
[2]レンギョウ属(Forsythia)に属する植物由来の抽出物が地上部由来の抽出物である、[1]に記載の発毛または育毛促進剤;
[3]レンギョウ属(Forsythia)に属する植物がヤマトレンギョウ(Forsythia japonica Makino)である、[1]または[2]に記載の発毛または育毛促進剤;
[4]オオバヒメマオ属(Pouzolzia)に属する植物由来の抽出物が地上部由来の抽出物である、[1]に記載の発毛または育毛促進剤;
[5]オオバヒメマオ属(Pouzolzia)に属する植物がオトギリマオ(Pouzolzia pentandra (Roxb.) Benn.)である、[1]または[4]に記載の発毛または育毛促進剤;
[6]サガリバナ属(Barringtonia)に属する植物由来の抽出物が樹皮由来の抽出物である、[1]に記載の発毛または育毛促進剤;
[7]サガリバナ属(Barringtonia)に属する植物がバリントニア・ペディセラタ(Barringtonia pedicellata Ridl.)である、[1]または[6]に記載の発毛または育毛促進剤;
[8]アノゲイスス属(Anogeissus)に属する植物由来の抽出物が樹皮由来の抽出物である、[1]に記載の発毛または育毛促進剤;
[9]アノゲイスス属(Anogeissus)に属する植物がヨン(Anogeissus acuminata Wall.)である、[1]または[8]に記載の発毛または育毛促進剤;
[10]ニワウルシ属(Ailanthus)に属する植物由来の抽出物が枝由来の抽出物である、[1]に記載の発毛または育毛促進剤;
[11]ニワウルシ属(Ailanthus)に属する植物がマラバルニワウルシ(Ailanthus triphysa (Dennst.) Alston)である、[1]または[10]に記載の発毛または育毛促進剤;
[12]コマツナギ属(Indigofera)に属する植物由来の抽出物が全草由来の抽出物である、[1]に記載の発毛または育毛促進剤;
[13]コマツナギ属(Indigofera)に属する植物がコマツナギ(Indigofera pseudotinctoria Matsum.)である、[1]または[12]に記載の発毛または育毛促進剤;
[14]抽出物が有機溶媒によって抽出された抽出物である、[1]〜[13]のいずれか1つに記載の発毛または育毛促進剤;
[15]有機溶媒が100%メタノールである、[14]に記載の発毛または育毛促進剤;
を提供する。
That is, the present invention
[1] At least one member belonging to the genus selected from the group consisting of Forsythia, Pouzolzia, Barringtonia, Anogeissus, Ailanthus and Indigofera Hair growth or hair growth promoter comprising an extract from one plant;
[2] The hair growth or hair growth promoter according to [1], wherein the plant-derived extract belonging to the genus Forsythia is an extract derived from the above-ground part;
[3] The hair growth or hair growth promoter according to [1] or [2], wherein the plant belonging to Forsythia is Forsythia japonica Makino;
[4] The hair growth or hair growth promoter according to [1], wherein the plant-derived extract belonging to the genus Pouzolzia is an extract derived from the aerial part;
[5] The hair growth or hair growth promoter according to [1] or [4], wherein the plant belonging to the genus Pouzolzia is Pouzolzia pentandra (Roxb.) Benn.
[6] The hair growth or hair growth promoter according to [1], wherein the plant-derived extract belonging to the genus Barringtonia is a bark-derived extract;
[7] The hair growth or hair growth promoter according to [1] or [6], wherein the plant belonging to the genus Barringtonia is Barringtonia pedicellata Ridl.
[8] The hair growth or hair growth promoter according to [1], wherein the plant-derived extract belonging to the genus Anogeissus is a bark-derived extract;
[9] The hair growth or hair growth promoting agent according to [1] or [8], wherein the plant belonging to the genus Anogeissus is Anogeissus acuminata Wall.
[10] The hair growth or hair growth promoter according to [1], wherein the plant-derived extract belonging to the genus Ailanthus is a branch-derived extract;
[11] The hair growth or hair growth promoter according to [1] or [10], wherein the plant belonging to the genus Ailanthus is Ailanthus triphysa (Dennst.) Alston;
[12] The hair growth or hair growth promoter according to [1], wherein the plant-derived extract belonging to the genus Indigofera is an extract derived from whole grass;
[13] The hair growth or hair growth promoter according to [1] or [12], wherein the plant belonging to the genus Indigofera is Indigofera pseudotinctoria Matsum.
[14] The hair growth or hair growth promoter according to any one of [1] to [13], wherein the extract is an extract extracted with an organic solvent;
[15] The hair growth or hair growth promoter according to [14], wherein the organic solvent is 100% methanol;
I will provide a.

レンギョウ属(Forsythia)、オオバヒメマオ属(Pouzolzia)、サガリバナ属(Barringtonia)、アノゲイスス属(Anogeissus)、ニワウルシ属(Ailanthus)およびコマツナギ属(Indigofera)からなる群から選択される属に属する少なくとも1つの植物由来の抽出物を、発毛または育毛促進剤として提供することができる。   From at least one plant belonging to the genus selected from the group consisting of Forsythia, Pouzolzia, Barringtonia, Anogeissus, Ailanthus and Indigofera Can be provided as a hair growth or hair growth promoter.

各試験群における各観察日のスコアの平均値を示すグラフである。It is a graph which shows the average value of the score of each observation day in each test group.

本発明は、レンギョウ属(Forsythia)、オオバヒメマオ属(Pouzolzia)、サガリバナ属(Barringtonia)、アノゲイスス属(Anogeissus)、ニワウルシ属(Ailanthus)およびコマツナギ属(Indigofera)からなる群から選択される属に属する少なくとも1つの植物由来の抽出物を含む、発毛または育毛促進剤を提供する。   The present invention is at least a genus selected from the group consisting of Forsythia, Pouzolzia, Barringtonia, Anogeissus, Ailanthus and Indigofera. A hair growth or hair growth promoting agent comprising an extract derived from one plant is provided.

本明細書においてレンギョウ属(Forsythia)に属する植物とは、レンギョウ属(Forsythia)に属する植物であれば、特に制限されず、例えば、ヤマトレンギョウ(Forsythia japonica Makino)、レンギョウ(Forsythia suspensa (Thunb.) Vahl)、シナレンギョウ(Forsythia viridissima Lindl.)、チョウセンレンギョウ(Forsythia viridissima Lindl. var. koreana Rehder)などが挙げられ、好ましくは、ヤマトレンギョウ(Forsythia japonica Makino)である。   In the present specification, the plant belonging to the genus Forsythia is not particularly limited as long as it belongs to the genus Forsythia, for example, Forsythia japonica Makino, Forsythia suspensa (Thunb.) Vahl), Forsythia viridissima Lindl., Forsythia viridissima Lindl. Var. Koreana Rehder, and the like, preferably Forsythia japonica Makino.

レンギョウ属(Forsythia)に属する植物由来の抽出物は、該植物全体に由来する抽出物であってもよいし、一部分に由来する抽出物であってもよい。一部分としては、地上部(例えば、幹、枝、樹皮、葉、花、果実および種子)または地下部(例えば、根)が挙げられる。本発明のレンギョウ属(Forsythia)に属する植物由来の抽出物は、地上部由来が好ましく、幼木であれば地上部全体、成木であれば枝及び葉などを用いることが好ましい。   The extract derived from a plant belonging to the Forsythia genus may be an extract derived from the whole plant or an extract derived from a part thereof. Some include the aerial parts (eg trunks, branches, bark, leaves, flowers, fruits and seeds) or the underground parts (eg roots). The plant-derived extract belonging to the genus Forsythia of the present invention is preferably derived from the above-ground part, and if it is a young tree, it is preferable to use the entire above-ground part, and if it is an adult tree, it uses branches and leaves.

本明細書においてオオバヒメマオ属(Pouzolzia)に属する植物とは、オオバヒメマオ属(Pouzolzia)に属する植物であれば、特に制限されず、例えば、オトギリマオ(Pouzolzia pentandra (Roxb.) Benn.)、オオバヒメマオ(Pouzolzia zeylanica (L.) Benn.)などが挙げられ、好ましくは、オトギリマオ(Pouzolzia pentandra (Roxb.) Benn.)である。   In the present specification, the plant belonging to the genus Pouzolzia is not particularly limited as long as it is a plant belonging to the genus Pouzolzia, for example, Pougolzia pentandra (Roxb.) Benn., Pouzolzia zeylanica. (L.) Benn.), And the like, preferably Pouzolzia pentandra (Roxb.) Benn.

オオバヒメマオ属(Pouzolzia)に属する植物由来の抽出物は、該植物全体に由来する抽出物であってもよいし、一部分に由来する抽出物であってもよい。一部分としては、地上部(例えば、幹、枝、樹皮、葉、花、果実および種子)または地下部(例えば、根)が挙げられる。本発明のオオバヒメマオ属(Pouzolzia)に属する植物由来の抽出物は、地上部由来が好ましく、幼木であれば地上部全体、成木であれば枝及び葉などを用いることが好ましい。   An extract derived from a plant belonging to the genus Pouzolzia may be an extract derived from the whole plant or an extract derived from a part thereof. Some include the aerial parts (eg trunks, branches, bark, leaves, flowers, fruits and seeds) or the underground parts (eg roots). The plant-derived extract belonging to the genus Pouzolzia of the present invention is preferably derived from the above-ground part, and if it is a young tree, the whole above-ground part is preferably used, and if it is an adult tree, it is preferable to use branches and leaves.

本明細書においてサガリバナ属(Barringtonia)に属する植物とは、サガリバナ属(Barringtonia)に属する植物であれば、特に制限されず、例えば、バリントニア・ペディセラタ(Barringtonia pedicellata Ridl.)、ゴバンノアシ(Barringtonia asiatica (L.) Kurz)などが挙げられ、好ましくは、バリントニア・ペディセラタ(Barringtonia pedicellata Ridl.)である。   In the present specification, the plant belonging to the genus Barringtonia is not particularly limited as long as it belongs to the genus Barringtonia, for example, Barringtonia pedicellata Ridl., Barringtonia asiatica (L .) Kurz) and the like, and preferably Barringtonia pedicellata Ridl.

サガリバナ属(Barringtonia)に属する植物由来の抽出物は、該植物全体に由来する抽出物であってもよいし、一部分に由来する抽出物であってもよい。一部分としては、地上部(例えば、幹、枝、樹皮、葉、花、果実および種子)または地下部(例えば、根)が挙げられる。本発明のサガリバナ属(Barringtonia)に属する植物由来の抽出物は、地上部由来が好ましく、樹皮由来がより好ましい。   The extract derived from a plant belonging to the genus Barringtonia may be an extract derived from the whole plant or an extract derived from a part thereof. Some include the aerial parts (eg trunks, branches, bark, leaves, flowers, fruits and seeds) or the underground parts (eg roots). The plant-derived extract belonging to the genus Barringtonia of the present invention is preferably derived from the above-ground part, and more preferably derived from bark.

本明細書においてアノゲイスス属(Anogeissus)に属する植物とは、アノゲイスス属(Anogeissus)に属する植物であれば、特に制限されず、例えば、ヨン(Anogeissus acuminata Wall.)、ガティノキ(Anogeissus latifolia)などが挙げられ、好ましくは、ヨン(Anogeissus acuminata Wall.)である。   In the present specification, the plant belonging to the genus Anogeissus is not particularly limited as long as it is a plant belonging to the genus Anogeissus. Yon (Anogeissus acuminata Wall.) Is preferable.

アノゲイスス属(Anogeissus)に属する植物由来の抽出物は、該植物全体に由来する抽出物であってもよいし、一部分に由来する抽出物であってもよい。一部分としては、地上部(例えば、幹、枝、樹皮、葉、花、果実および種子)または地下部(例えば、根)が挙げられる。本発明のアノゲイスス属(Anogeissus)に属する植物由来の抽出物は、地上部由来が好ましく、樹皮由来がより好ましい。   An extract derived from a plant belonging to the genus Anogeissus may be an extract derived from the whole plant or an extract derived from a part thereof. Some include the aerial parts (eg trunks, branches, bark, leaves, flowers, fruits and seeds) or the underground parts (eg roots). The plant-derived extract belonging to the genus Anogeissus of the present invention is preferably derived from the above-ground part, and more preferably derived from bark.

本明細書においてニワウルシ属(Ailanthus)に属する植物とは、ニワウルシ属(Ailanthus)に属する植物であれば、特に制限されず、例えば、マラバルニワウルシ(Ailanthus triphysa (Dennst.) Alston)、ニワウルシ(Ailanthus altissima (Mill.) Swingle)などが挙げられ、好ましくは、マラバルニワウルシ(Ailanthus triphisa (Dennst.) Alston)である。   In the present specification, the plant belonging to the genus Ailanthus is not particularly limited as long as it is a plant belonging to the genus Ailanthus, for example, Ailanthus triphysa (Dennst.) Alston, Ailanthus altissima (Mill.) Swingle) and the like, preferably Ailanthus triphisa (Dennst.) Alston.

ニワウルシ属(Ailanthus)に属する植物由来の抽出物は、該植物全体に由来する抽出物であってもよいし、一部分に由来する抽出物であってもよい。一部分としては、地上部(例えば、幹、枝、樹皮、葉、花、果実および種子)または地下部(例えば、根)が挙げられる。本発明のニワウルシ属(Ailanthus)に属する植物由来の抽出物は、地上部由来が好ましく、枝由来がより好ましい。   The extract derived from a plant belonging to the genus Ailanthus may be an extract derived from the whole plant or an extract derived from a part thereof. Some include the aerial parts (eg trunks, branches, bark, leaves, flowers, fruits and seeds) or the underground parts (eg roots). The plant-derived extract belonging to the genus Ailanthus of the present invention is preferably derived from the above-ground part, and more preferably derived from a branch.

本明細書においてコマツナギ属(Indigofera)に属する植物とは、コマツナギ属(Indigofera)に属する植物であれば、特に制限されず、例えば、コマツナギ(Indigofera pseudotinctoria Matsum.)、ギンアイ(Indigofera argentea)、ナンバンコマツナギ(Indigofera suffruticosa Mill.)、タイワンコマツナギ(Indigofera tinctoria L.)、ニワフジ(Indigofera decora Lindl.)、コダチニワフジ(Indigofera heterantha)などが挙げられ、好ましくは、コマツナギ(Indigofera pseudotinctoria Matsum.)である。   In the present specification, the plant belonging to the genus Indigofera is not particularly limited as long as it is a plant belonging to the genus Indigofera, for example, Indigofera pseudotinctoria Matsum., Indigofera argentea, Namban Komatsuna (Indigofera suffruticosa Mill.), Taiwan Komatsunagi (Indigofera tinctoria L.), Niwafuji (Indigofera decora Lindl.), Kodachiniwafuji (Indigofera heterantha), etc., and Komatsunagi (Indigofera pseudotinctoria Matsum.) Is preferred.

コマツナギ属(Indigofera)に属する植物由来の抽出物は、該植物全体(全草)に由来する抽出物であってもよいし、一部分に由来する抽出物であってもよい。一部分としては、地上部(例えば、茎、葉、花、果実および種子)または地下部(例えば、根)が挙げられる。本発明のコマツナギ属(Indigofera)に属する植物由来の抽出物は、全草由来が好ましい。   The plant-derived extract belonging to the genus Indigofera may be an extract derived from the whole plant (whole plant) or an extract derived from a part thereof. Some include the aerial parts (eg stems, leaves, flowers, fruits and seeds) or the underground parts (eg roots). The plant-derived extract belonging to the genus Indigofera of the present invention is preferably derived from whole plants.

本発明のレンギョウ属(Forsythia)、オオバヒメマオ属(Pouzolzia)、サガリバナ属(Barringtonia)、アノゲイスス属(Anogeissus)、ニワウルシ属(Ailanthus)およびコマツナギ属(Indigofera)からなる群から選択される属に属する植物由来の抽出物は、公知の抽出方法で抽出することができる。   Derived from a plant belonging to the genus selected from the group consisting of Forsythia, Pouzolzia, Barringtonia, Anogeissus, Ailanthus and Indigofera of the present invention The extract can be extracted by a known extraction method.

抽出前の植物は、抽出作業の直前に採取してもよいし、予め採取し、乾燥処置等を施して保存されたものであってもよい。また、抽出前は、適度に細断又は粉砕した状態にして抽出に用いることが望ましい。あるいは、磨砕、擂潰、粉末化等した状態にして抽出に用いても良い。   The plant before extraction may be collected immediately before the extraction operation, or may be collected in advance and stored after being subjected to a drying treatment or the like. Moreover, before extraction, it is desirable to use it for extraction after appropriately chopped or pulverized. Alternatively, it may be used for extraction after being ground, crushed, or powdered.

抽出に用いる溶媒としては、有機溶媒が挙げられる。抽出溶媒としては、通常、エタノール、メタノール、アセトンなどから選ばれた1種以上の親水性有機溶媒又はその水溶液(含水有機溶媒)を用いることができ、その中でもメタノールが好ましい。抽出溶媒として、100%有機溶媒を用いることが好ましい。また抽出溶媒として有機溶媒水溶液(含水有機溶媒)を使用する場合は、有機溶媒濃度20〜80%、好ましくは30〜70%、より好ましくは40〜60%、さらに好ましくは45〜55%の有機溶媒水溶液(含水有機溶媒)を用いることが望ましい。
抽出溶媒の使用量としては、植物(重量)に対して前記抽出溶媒を2〜50倍量、好ましくは5〜25倍量が好適である。
An organic solvent is mentioned as a solvent used for extraction. As the extraction solvent, one or more hydrophilic organic solvents selected from ethanol, methanol, acetone and the like or an aqueous solution thereof (water-containing organic solvent) can be used. Of these, methanol is preferable. It is preferable to use a 100% organic solvent as the extraction solvent. When an organic solvent aqueous solution (hydrous organic solvent) is used as the extraction solvent, the organic solvent concentration is 20 to 80%, preferably 30 to 70%, more preferably 40 to 60%, still more preferably 45 to 55%. It is desirable to use a solvent aqueous solution (hydrous organic solvent).
The amount of the extraction solvent used is 2 to 50 times, preferably 5 to 25 times the amount of the extraction solvent relative to the plant (weight).

抽出時間としては、常温(10〜30℃)で行う場合は、1日以上、好ましくは2日以上、より好ましくは3日以上、さらに好ましくは5日以上、特に好ましくは7日以上行うことが望ましい。上限としては、14日以内、好ましくは10日以内が目安である。
加熱条件(例えば40〜80℃)で抽出を行う場合は、0.5〜48時間、好ましくは1〜24時間、より好ましくは1.5〜12時間、さらに好ましくは2〜10時間、特に好ましくは3〜8時間かけて行うことが好ましい。
当該抽出操作は静置で十分であるが、好ましくは撹拌や混合を行うことが望ましい。また、メタノール又は含水メタノールを抽出溶媒として用いる場合は、高温加熱還流させて行ってもよい。
The extraction time is 1 day or more, preferably 2 days or more, more preferably 3 days or more, further preferably 5 days or more, particularly preferably 7 days or more when performed at room temperature (10 to 30 ° C.). desirable. The upper limit is within 14 days, preferably within 10 days.
When the extraction is performed under heating conditions (for example, 40 to 80 ° C.), 0.5 to 48 hours, preferably 1 to 24 hours, more preferably 1.5 to 12 hours, further preferably 2 to 10 hours, and particularly preferably 3 to 8 hours. It is preferable to carry out over time.
The extraction operation may be left still, but it is desirable to perform stirring and mixing. Moreover, when using methanol or hydrous methanol as an extraction solvent, you may carry out by heating-refluxing at high temperature.

抽出後、懸濁液から濾過等により固形分を分離して得られた抽出物は、そのまま、又は必要により濃縮、乾燥して本発明の発毛または育毛促進剤として用いることができる。本明細書において発毛促進とは、毛周期において、休止期から成長期への移行期間を短縮させることをいう。また、本明細書において育毛促進とは、毛髪の成長速度を向上させることをいう。上記の溶媒で抽出された抽出液は、その純度で、本発明の発毛または育毛促進剤として有用であるが、更に自体公知の方法により精製しても良い。   After the extraction, the extract obtained by separating the solid content from the suspension by filtration or the like can be used as it is or after concentration and drying as necessary, as the hair growth or hair growth promoter of the present invention. In this specification, hair growth promotion means shortening the transition period from the resting phase to the growth phase in the hair cycle. Moreover, in this specification, hair growth promotion means improving the growth rate of hair. The extract extracted with the above solvent is useful as a hair growth or hair growth promoter of the present invention because of its purity, but may be further purified by a method known per se.

さらに、当該抽出物は、濃縮等を行って親水性有機溶媒や水分を除去した後、親油性有機溶媒を用いて液-液抽出を行ってもよい。ここで親油性有機溶媒としては、酢酸エチル、ジエチルエーテル、ベンゼン、トルエン、キシレンなどが挙げられる。
親油性有機溶媒の使用量としては、植物(重量)に対して0.1〜3倍量、好ましくは0.2〜2倍量、より好ましくは0.3〜1倍量が好適である。当該操作は撹拌混合した後に静置して行えば良い。
分配操作としては、例えば、液-液向流分配が適当である。当該有機溶媒層を分取し、溶媒を留去して乾燥すると、発毛促進活性および育毛促進活性を有する抽出物が得られる。
Further, the extract may be subjected to liquid-liquid extraction using a lipophilic organic solvent after concentration or the like is performed to remove the hydrophilic organic solvent or moisture. Examples of the lipophilic organic solvent include ethyl acetate, diethyl ether, benzene, toluene, xylene and the like.
The amount of the lipophilic organic solvent used is preferably 0.1 to 3 times, preferably 0.2 to 2 times, more preferably 0.3 to 1 times the amount of the plant (weight). The operation may be performed after stirring and mixing.
As the distribution operation, for example, liquid-liquid countercurrent distribution is appropriate. When the organic solvent layer is collected, and the solvent is distilled off and dried, an extract having hair growth promoting activity and hair growth promoting activity is obtained.

本発明の抽出物は、発毛促進活性および育毛促進活性を有する成分の作用により、頭皮に外用塗布することで顕著な発毛および育毛効果が発揮される。従って、本発明の抽出物は、発毛または育毛促進剤として使用することができる。   The extract of the present invention exhibits remarkable hair growth and hair growth effects when applied externally to the scalp due to the action of components having hair growth promotion activity and hair growth promotion activity. Therefore, the extract of the present invention can be used as a hair growth or hair growth promoter.

本発明の発毛または育毛促進剤に含まれる本発明の抽出物は、レンギョウ属(Forsythia)、オオバヒメマオ属(Pouzolzia)、サガリバナ属(Barringtonia)、アノゲイスス属(Anogeissus)、ニワウルシ属(Ailanthus)およびコマツナギ属(Indigofera)からなる群から選択される属に属する少なくとも1つの植物由来の抽出物であってよい。本発明の発毛または育毛促進剤は、例えば、2つの植物由来の抽出物、3つの植物由来の抽出物、4つの植物由来の抽出物、5つ以上の植物由来の抽出物を含むものであってもよい。   The extract of the present invention contained in the hair growth or hair growth promoting agent of the present invention includes Forsythia, Pouzolzia, Barringtonia, Anogeissus, Ailanthus and Komatsunagi. It may be an extract from at least one plant belonging to the genus selected from the group consisting of the genus (Indigofera). The hair growth or hair growth promoter of the present invention includes, for example, two plant-derived extracts, three plant-derived extracts, four plant-derived extracts, and five or more plant-derived extracts. There may be.

本発明の発毛または育毛促進剤は、ヒト、ヒト以外の動物(例えば、ヒト以外の哺乳類(ブタ、ウシ、ウマ、イヌ、ネコ等の家畜)、鳥類(シチメンチョウ、ニワトリ等の家禽)等)等に適用することが有用である。   The hair growth or hair growth promoter of the present invention is a human, non-human animal (eg, non-human mammals (domestic animals such as pigs, cows, horses, dogs, cats), birds (turkeys such as turkeys and chickens), etc.) Etc. are useful.

本発明の抽出物は、エタノール、つばき油などの油脂類、クリームなどに溶解して、発毛または育毛促進剤として使用することができる。
抽出物の配合量としては、固形分換算で、発毛または育毛促進剤重量の全体の0.001%(w/w)以上、好ましくは0.01(w/w)以上、より好ましくは0.1%(w/w)以上の割合で配合することが好適である。配合量が少なすぎる場合、発毛または育毛促進効果が十分に得られず好ましくない。
上限としては、例えば、5%(w/w)以下、好ましくは2%(w/w)以下を挙げることができる。
The extract of the present invention can be dissolved in oils and fats such as ethanol and camellia oil, creams and the like and used as a hair growth or hair growth promoter.
The blending amount of the extract is 0.001% (w / w) or more, preferably 0.01 (w / w) or more, more preferably 0.1% (w / w) of the total weight of the hair growth or hair growth promoter in terms of solid content. It is preferable to blend in the proportion of w) or more. When the blending amount is too small, the effect of promoting hair growth or hair growth cannot be sufficiently obtained, which is not preferable.
Examples of the upper limit include 5% (w / w) or less, preferably 2% (w / w) or less.

また、当該発毛または育毛促進剤に配合する他の原料成分としては、通常の発毛または育毛促進剤に適用されるものを用いることができる。例えば、炭化水素類、ロウ類、油脂類、エステル類、高級脂肪酸類、高級アルコール類、界面活性剤、香料、色素、防腐剤、保存剤、賦形剤、清涼剤、湿潤剤、抗酸化剤、紫外線防御剤、アルコール類、pH調整剤などを配合することができる。また、他の発毛または育毛促進剤である表皮の角質溶解剤、血行促進剤、細胞賦活剤、局所刺激剤などを配合することができる。また、殺菌剤、消炎剤、抗脂漏剤、止痒剤などを配合することができる。   Moreover, as another raw material component mix | blended with the said hair growth or hair growth promoter, what is applied to normal hair growth or a hair growth promoter can be used. For example, hydrocarbons, waxes, fats and oils, esters, higher fatty acids, higher alcohols, surfactants, fragrances, pigments, preservatives, preservatives, excipients, cooling agents, wetting agents, antioxidants , UV protective agents, alcohols, pH adjusters and the like can be blended. In addition, other epidermal keratolytic agents, blood circulation promoters, cell activators, local stimulants, and the like, which are other hair growth or hair growth promoters, can be blended. Moreover, a disinfectant, an anti-inflammatory agent, an antiseborrheic agent, an antidiarrheal agent, etc. can be mix | blended.

本発明の発毛または育毛促進剤は、頭皮に対して外用塗布が可能な形態であれば如何なる形態であってもよい。例えば、医薬品又は医薬部外品として、クリーム、軟膏、ローション等の形態とすることができる。   The hair growth or hair growth promoter of the present invention may be in any form as long as it can be externally applied to the scalp. For example, it can be in the form of cream, ointment, lotion, etc. as a medicine or quasi drug.

本発明の発毛または育毛促進剤はまた、頭髪用化粧品、整髪料、又は洗髪料の成分として配合することができる。例えば、ヘアクリーム、ヘアトニック、ヘアローション、ヘアーリキッド、ヘアコンディショナー、ヘアトリートメント、ヘアスプレー、シャンプー、リンス、シャンプーアンドリンスなどに配合することができる。
この場合の含有量としては、上記発毛または育毛促進剤で挙げた配合量の範囲に準じて調整することが望ましい。配合量が少なすぎる場合、発毛または育毛促進効果が十分に得られず好ましくない。
なお、頭髪用化粧品、整髪料、洗髪料に配合するその他の原料成分としては、通常の製造に用いる原料成分を配合することができる。
The hair growth or hair growth-promoting agent of the present invention can also be blended as a component of a cosmetic product for hair, a hair styling product, or a hair washing product. For example, it can be blended in hair cream, hair tonic, hair lotion, hair liquid, hair conditioner, hair treatment, hair spray, shampoo, rinse, shampoo and rinse.
The content in this case is desirably adjusted according to the range of the blending amount mentioned in the hair growth or hair growth promoter. When the blending amount is too small, the effect of promoting hair growth or hair growth cannot be sufficiently obtained, which is not preferable.
In addition, the raw material component used for normal manufacture can be mix | blended as another raw material component mix | blended with cosmetics for hair, a hairdressing agent, and a hair-washing agent.

以下において、実施例により本発明をより具体的にするが、この発明はこれらに限定されるものではない。   In the following, the present invention will be more specifically described with reference to examples, but the present invention is not limited thereto.

実施例1 発毛活性の評価
C3H/HeNマウスは、生後45日から背部体毛の毛周期が休止期に入ることが知られている。休止期は通常、生後90日までに続き、その後、毛周期は成長期に入る。本実施例においては、毛周期が休止期であるC3H/HeNマウスの背部体毛を剃毛し、該剃毛部分に試験化合物を塗布し、休止期から成長期への移行期間を測定することによって、該試験化合物の発毛活性を評価した。
Example 1 Evaluation of hair growth activity
In C3H / HeN mice, it is known that the hair cycle of the dorsal body hair enters a resting phase from 45 days after birth. The rest period usually lasts until 90 days after birth, after which the hair cycle enters the growth period. In this example, by shaving the back body hair of C3H / HeN mice whose hair cycle is at rest, applying a test compound to the shaved portion, and measuring the transition period from rest to growth The hair growth activity of the test compound was evaluated.

試験化合物
生薬として表1に記載の植物の各部位を細断または破砕し、60℃で一晩乾燥させ、乾燥重量で500gを秤量した。該乾燥生薬に該乾燥重量の5〜25倍量の100%メタノールを加えて、室温で一週間、時々撹拌しながら静置し、有効成分を溶出させた。該溶液をろ紙(No.2)で濾過し、エバポレーターで濃縮し、凍結乾燥機を用いて乾燥粉末を得た。該乾燥粉末を試験化合物として、滅菌蒸留水およびエタノールをそれぞれ等量混合した溶媒(以下、50% EtOH)に溶解し、各試験化合物含有溶液(1% w/v)(#1801, #3126, #543, #330, #133, #2112)を得た。また、コントロールとして、上記の50% EtOHを用いた。
Each part of the plant described in Table 1 as a test compound crude drug was shredded or crushed, dried overnight at 60 ° C., and weighed 500 g in dry weight. 100% methanol of 5 to 25 times the dry weight was added to the dry herbal medicine and allowed to stand at room temperature for 1 week with occasional stirring to elute the active ingredients. The solution was filtered through a filter paper (No. 2), concentrated by an evaporator, and a dry powder was obtained using a freeze dryer. Using the dry powder as a test compound, each of the test compound-containing solutions (1% w / v) (# 1801, # 3126, # 543, # 330, # 133, # 2112). As a control, the above 50% EtOH was used.

実験手順
8週齢のC3H/HeN雄マウス(日本SLC)を1週間馴化させた後、背部領域から毛衣を刈り取った。剃毛した皮膚表面の色が桃色であるマウスを毛周期が休止期であるマウスとして各試験群(50% EtOH, #1801, #3126, #543, #330, #133, #2112)に分けた。
上記の各試験化合物含有溶液または50% EtOHを、各試験群の剃毛した背部領域に、塗布量が6.7μL/cm2かつ100μL/匹になるように毛流に逆らって塗布した。塗布は、1回/日で5日間/週ずつ実施した。
剃毛し、最初に各試験化合物含有溶液または50% EtOHをマウスに塗布した日をday 0とし、day 1, 6, 8, 12, 14, 16, 17においてマウスを観察し、各試験化合物の発毛活性の評価を行った。発毛活性の評価は、塗布領域における毛成長の兆候を観察し、観察結果に基づくスコアを算出することによって実施した。毛成長の兆候としては、毛包中のメラノサイトがメラニンを合成し、皮膚の色が桃色から灰色に変化することが挙げられる。従って、各観察日において皮膚の色の変化した面積または毛の伸長が見られた面積に基づいてスコアを割り当てることによって、各試験化合物の発毛活性の評価を行った。皮膚の色の変化面積または毛の伸長面積とスコアの関係を表2に示す。また、各試験群における各観察日のスコアの平均値を表3および図1に示す。
Experimental Procedure After acclimating an 8-week-old C3H / HeN male mouse (Japan SLC) for 1 week, the fur coat was cut from the back region. Mice whose shaved skin surface is pink are divided into test groups (50% EtOH, # 1801, # 3126, # 543, # 330, # 133, # 2112) as mice with a resting hair cycle. It was.
Each test compound-containing solution or 50% EtOH was applied against the hair flow so that the application amount was 6.7 μL / cm 2 and 100 μL / animal on the shaved back region of each test group. Application was carried out once / day for 5 days / week.
The day when the mice were shaved and each test compound-containing solution or 50% EtOH was first applied to the mice was defined as day 0, and the mice were observed on days 1, 6, 8, 12, 14, 16, 17 The hair growth activity was evaluated. The evaluation of hair growth activity was carried out by observing signs of hair growth in the application area and calculating a score based on the observation results. As an indication of hair growth, melanocytes in the hair follicle synthesize melanin and the skin color changes from pink to gray. Therefore, the hair growth activity of each test compound was evaluated by assigning a score based on the area where the skin color changed or the area where hair elongation was observed on each observation day. Table 2 shows the relationship between the skin color change area or the hair extension area and the score. Moreover, the average value of the score of each observation day in each test group is shown in Table 3 and FIG.

実施例2 育毛活性の評価
C57BL6/Nマウスは、背部体毛を抜毛すると、抜毛領域の毛周期が強制的に退行期に移行され、結果として抜毛領域の毛周期が同期化されることが知られている(Ya-Chieh Hsu et al., Cell, 144, 92-105, 2011)。抜毛後7日程で、成長期の兆候として、色素のある毛の生成に加え、毛包中のメラノサイトがメラニンを合成し始めるにつれ、皮膚が灰色に変色する様子が観察される。さらに、抜毛後10日後程で、抜毛領域における発毛が確認される。本実施例においては、C57BL6/Nマウスの背部体毛を脱毛し、該脱毛部分に試験化合物を塗布し、成長期における1日当たりの毛の伸長速度を測定することによって、該試験化合物の育毛活性を評価した。
Example 2 Evaluation of Hair Growth Activity
In C57BL6 / N mice, it is known that when the dorsal body hair is removed, the hair cycle of the hair removal region is forcibly shifted to the regression phase, and as a result, the hair cycle of the hair removal region is synchronized (Ya-Chieh Hsu et al., Cell, 144, 92-105, 2011). About 7 days after hair removal, as a sign of the growth period, it is observed that the skin turns gray as melanocytes in the hair follicle begin to synthesize melanin in addition to the production of pigmented hair. Furthermore, hair growth in the hair removal region is confirmed about 10 days after hair removal. In this example, the back hair of C57BL6 / N mice was depilated, a test compound was applied to the depigmented portion, and the hair growth activity of the test compound was measured by measuring the hair growth rate per day during the growth phase. evaluated.

試験化合物
実施例1と同様の試験化合物を使用し、同様の手法で各試験化合物含有溶液(1% w/v)(#1801, #3126, #543, #330, #133, #2112)を調製した。また、コントロールとして、50% EtOHを用いた。
Test compound Using the same test compound as in Example 1, each test compound-containing solution (1% w / v) (# 1801, # 3126, # 543, # 330, # 133, # 2112) was prepared in the same manner. Prepared. As a control, 50% EtOH was used.

実験手順
7週齢のC57BL6/N雌マウス(日本SLC)を1週間馴化させた後に抜毛し、脱毛した皮膚表面の色が桃色であるマウスを各試験群(50% EtOH, #1801, #3126, #543, #330, #133, #2112)に分けた。
上記の各試験化合物含有溶液または50% EtOHを、各試験群の抜毛した背部領域に、塗布量が6.7μL/cm2かつ100μL/匹になるように毛流に逆らって塗布した。塗布は、1回/日で5日間/週ずつ実施した。
脱毛し、最初に各試験化合物含有溶液または50% EtOHをマウスに塗布し、発毛後のマウスを観察し、各試験化合物の育毛活性の評価を行った。育毛活性の評価は、塗布領域における毛を定期的に採取し、発毛後4日目から12日目の間における1日あたりのマウス背部体毛の平均伸長速度を計測することによって実施した。各試験群における伸長速度の平均値を表4に示す。
Experimental procedure Seven-week-old C57BL6 / N female mice (Japan SLC) were acclimated for one week, and then hair was removed, and mice with hair color pink were removed from each test group (50% EtOH, # 1801, # 3126). , # 543, # 330, # 133, # 2112).
Each test compound-containing solution or 50% EtOH was applied against the hair flow so that the application amount was 6.7 μL / cm 2 and 100 μL / animal to the back region of each test group. Application was carried out once / day for 5 days / week.
First, each test compound-containing solution or 50% EtOH was applied to the mice, and the mice after hair growth were observed to evaluate the hair-growth activity of each test compound. Evaluation of hair growth activity was carried out by periodically collecting hair in the application area and measuring the average elongation rate of the mouse back body hair per day during the 4th to 12th days after hair growth. Table 4 shows the average value of the elongation rate in each test group.

本発明のレンギョウ属(Forsythia)、オオバヒメマオ属(Pouzolzia)、サガリバナ属(Barringtonia)、アノゲイスス属(Anogeissus)、ニワウルシ属(Ailanthus)、コマツナギ属(Indigofera)に属する植物由来の抽出物は、毛周期の休止期から成長期への移行期間を短縮する効果(発毛促進効果)および毛の伸長速度を高める効果(育毛促進効果)を有するため、発毛または育毛促進剤として利用できる。   An extract derived from a plant belonging to the genus Forsythia, the genus Pouzolzia, the genus Barringtonia, the genus Anogiesus, the genus Ailanthus, and the genus Indigofera has a hair cycle. Since it has the effect of shortening the transition period from the rest period to the growth period (hair growth promoting effect) and the effect of increasing the hair elongation rate (hair growth promoting effect), it can be used as a hair growth or hair growth promoting agent.

Claims (15)

レンギョウ属(Forsythia)、オオバヒメマオ属(Pouzolzia)、サガリバナ属(Barringtonia)、アノゲイスス属(Anogeissus)、ニワウルシ属(Ailanthus)およびコマツナギ属(Indigofera)からなる群から選択される属に属する少なくとも1つの植物由来の抽出物を含む、発毛または育毛促進剤。   From at least one plant belonging to the genus selected from the group consisting of Forsythia, Pouzolzia, Barringtonia, Anogeissus, Ailanthus and Indigofera A hair growth or hair growth promoter comprising an extract of レンギョウ属(Forsythia)に属する植物由来の抽出物が地上部由来の抽出物である、請求項1に記載の発毛または育毛促進剤。   The hair growth or hair growth-promoting agent according to claim 1, wherein the plant-derived extract belonging to the Forsythia genus is an above-ground extract. レンギョウ属(Forsythia)に属する植物がヤマトレンギョウ(Forsythia japonica Makino)である、請求項1または2に記載の発毛または育毛促進剤。   The hair growth or hair growth promoter according to claim 1 or 2, wherein the plant belonging to Forsythia is Forsythia japonica Makino. オオバヒメマオ属(Pouzolzia)に属する植物由来の抽出物が地上部由来の抽出物である、請求項1に記載の発毛または育毛促進剤。   The hair growth or hair growth promoter according to claim 1, wherein the plant-derived extract belonging to the genus Pouzolzia is an extract derived from the above-ground part. オオバヒメマオ属(Pouzolzia)に属する植物がオトギリマオ(Pouzolzia pentandra (Roxb.) Benn.)である、請求項1または4に記載の発毛または育毛促進剤。   The hair growth or hair growth promoter according to claim 1 or 4, wherein the plant belonging to the genus Pouzolzia is Pouzolzia pentandra (Roxb.) Benn. サガリバナ属(Barringtonia)に属する植物由来の抽出物が樹皮由来の抽出物である、請求項1に記載の発毛または育毛促進剤。   The hair growth or hair growth promoter according to claim 1, wherein the plant-derived extract belonging to the genus Barringtonia is an extract derived from bark. サガリバナ属(Barringtonia)に属する植物がバリントニア・ペディセラタ(Barringtonia pedicellata Ridl.)である、請求項1または6に記載の発毛または育毛促進剤。   The hair growth or hair growth promoter according to claim 1 or 6, wherein the plant belonging to the genus Barringtonia is Barringtonia pedicellata Ridl. アノゲイスス属(Anogeissus)に属する植物由来の抽出物が樹皮由来の抽出物である、請求項1に記載の発毛または育毛促進剤。   The hair growth or hair growth-promoting agent according to claim 1, wherein the plant-derived extract belonging to the genus Anogeissus is a bark-derived extract. アノゲイスス属(Anogeissus)に属する植物がヨン(Anogeissus acuminata Wall.)である、請求項1または8に記載の発毛または育毛促進剤。   The hair growth or hair growth promoter according to claim 1 or 8, wherein the plant belonging to the genus Anogeissus is Anogeissus acuminata Wall. ニワウルシ属(Ailanthus)に属する植物由来の抽出物が枝由来の抽出物である、請求項1に記載の発毛または育毛促進剤。   The hair growth or hair growth promoter according to claim 1, wherein the plant-derived extract belonging to the genus Ailanthus is a branch-derived extract. ニワウルシ属(Ailanthus)に属する植物がマラバルニワウルシ(Ailanthus triphysa (Dennst.) Alston)である、請求項1または10に記載の発毛または育毛促進剤。   The hair growth or hair growth promoter according to claim 1 or 10, wherein the plant belonging to the genus Ailanthus is Ailanthus triphysa (Dennst.) Alston. コマツナギ属(Indigofera)に属する植物由来の抽出物が全草由来の抽出物である、請求項1に記載の発毛または育毛促進剤。   The hair growth or hair growth promoting agent according to claim 1, wherein the plant-derived extract belonging to the genus Indigofera is an extract derived from whole grass. コマツナギ属(Indigofera)に属する植物がコマツナギ(Indigofera pseudotinctoria Matsum.)である、請求項1または12に記載の発毛または育毛促進剤。   The hair growth or hair growth promoter according to claim 1 or 12, wherein the plant belonging to the genus Indigofera is Indigofera pseudotinctoria Matsum. 抽出物が有機溶媒によって抽出された抽出物である、請求項1〜13のいずれか1項に記載の発毛または育毛促進剤。   The hair growth or hair growth promoter according to any one of claims 1 to 13, wherein the extract is an extract extracted with an organic solvent. 有機溶媒が100%メタノールである、請求項14に記載の発毛または育毛促進剤。   The hair growth or hair growth promoter according to claim 14, wherein the organic solvent is 100% methanol.
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