JP6563175B2 - VEGF production promoter, hair growth and / or hair growth promoter - Google Patents
VEGF production promoter, hair growth and / or hair growth promoter Download PDFInfo
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- JP6563175B2 JP6563175B2 JP2014067274A JP2014067274A JP6563175B2 JP 6563175 B2 JP6563175 B2 JP 6563175B2 JP 2014067274 A JP2014067274 A JP 2014067274A JP 2014067274 A JP2014067274 A JP 2014067274A JP 6563175 B2 JP6563175 B2 JP 6563175B2
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- aloe
- hair growth
- hair
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- growth
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Description
本発明は、アロエエキスを有効成分とするＶＥＧＦ産生促進剤に関する。 The present invention relates to a VEGF production promoter containing aloe extract as an active ingredient.
また、本発明は、アロエエキスを有効成分とする育毛及び／又は発毛促進剤に関する。 Moreover, this invention relates to the hair growth and / or hair growth promoter which uses an aloe extract as an active ingredient.
血管内皮増殖因子（VEGF、vascular endothelial growth factor）は、下垂体星状濾胞細胞の培養液より単離された、血管内皮細胞に特異的に作用する増殖因子である。そして、VEGFの産生細胞として、下垂体星状濾胞細胞はもとより、マクロファージ、平滑筋細胞、胚線維芽細胞等の多様な正常細胞、並びに腫瘍細胞の報告がある。 Vascular endothelial growth factor (VEGF) is a growth factor isolated from a culture medium of pituitary astrocytes and specifically acting on vascular endothelial cells. As VEGF producing cells, there are reports of not only pituitary astrocytes, but also various normal cells such as macrophages, smooth muscle cells, embryonic fibroblasts, and tumor cells.
毛髪には毛周期があることが知られており、成長期、退行期及び休止期からなる周期的なヘアサイクル（毛周期）に従って、成長と脱落とを繰り返している。そして、薄毛及び脱毛を防止する、又は進行を止めるためには、毛髪が休止期から速やかに成長期に移行されることが重要であると考えられる。これら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。 It is known that hair has a hair cycle, and growth and shedding are repeated according to a periodic hair cycle (hair cycle) consisting of a growth phase, a regression phase, and a resting phase. And, in order to prevent thinning and hair loss or to stop progress, it is considered important that the hair is promptly shifted from the rest period to the growth period. It is considered that hair papilla cells play an important role in the proliferation and differentiation of hair follicle epithelial cells in these stages.
毛は、毛包角化細胞の増殖、分化（角化）により形成される。そして、毛乳頭（毛乳頭細胞）は、毛包角化細胞の増殖、分化及びアポトーシスを制御し、毛周期調節の中心的な役割を担っている。この毛乳頭には毛細血管が入りこんでおり、毛細血管は栄養供給等の役割を果している。また、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る。 Hair is formed by the proliferation and differentiation (keratinization) of hair follicle keratinocytes. The hair papilla (hair papilla cell) controls the proliferation, differentiation and apoptosis of hair follicle keratinocytes and plays a central role in hair cycle regulation. Capillaries have entered the nipples, and the capillaries play a role in nutrient supply and the like. 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.
毛乳頭細胞についての報告は多く、例えば、毛乳頭細胞は、成長期に毛乳頭内の血管内皮細胞、つまり毛細血管を構成する細胞を増殖することが報告されている（非特許文献１）。また、アスペルギルス菌から見つかった血管新生阻害剤（TNP-470）をマウスの腹腔に注射した場合、体毛の毛周期が遅れ、成長期が始まらないことが報告されている（非特許文献２）。 There have been many reports on dermal papilla cells. For example, it has been reported that dermal papilla cells proliferate vascular endothelial cells in the dermal papilla, that is, cells constituting capillaries during the growth phase (Non-patent Document 1). It has also been reported that when an angiogenesis inhibitor (TNP-470) found from Aspergillus is injected into the abdominal cavity of a mouse, the hair cycle of body hair is delayed and the growth phase does not start (Non-patent Document 2).
一方、毛包では、外毛根鞘細胞及び毛乳頭細胞がVEGFを発現することが報告されている（非特許文献３及び４）。また、毛周期の進行には毛乳頭細胞が重要な役割を担っており、毛乳頭細胞から産生される種々の因子（血管内皮増殖因子（VEGF）、線維芽細胞増殖因子-7（FGF-7）等）が、成長期の維持や成長期から退行期及び休止期への移行に関与していると考えられている。また、VEGFの動きを阻害する特異抗体をマウス腹腔に注射すると、成長期が遅れるとともに毛包のサイズが小さくなり、毛包の発達や再生に血管新生が重要であることが報告されている（非特許文献５）。反対に、外毛根鞘でのVEGF合成量を増加させた場合、毛包のサイズが増大し、作られる毛の直径も太くなることが報告されている。更に、毛乳頭細胞から産生されるVEGFは発毛を促進することや、医薬品の育毛剤に用いられているミノキシジルの作用に関与すること等が知られている（非特許文献６）。 On the other hand, in hair follicles, it has been reported that outer root sheath cells and dermal papilla cells express VEGF (Non-patent Documents 3 and 4). In addition, dermal papilla cells play an important role in the progression of the hair cycle, and various factors produced from dermal papilla cells (vascular endothelial growth factor (VEGF), fibroblast growth factor-7 (FGF-7)) ) Etc.) are considered to be involved in maintaining the growth period and transitioning from the growth period to the regression and rest periods. It has also been reported that when a specific antibody that inhibits VEGF movement is injected into the abdominal cavity of mice, the growth phase is delayed and the size of the hair follicle is reduced, and angiogenesis is important for hair follicle development and regeneration ( Non-patent document 5). On the other hand, it has been reported that when the amount of VEGF synthesis in the outer root sheath increases, the size of the hair follicle increases and the diameter of the hair produced increases. Furthermore, it is known that VEGF produced from dermal papilla cells promotes hair growth and is involved in the action of minoxidil used in pharmaceutical hair restorers (Non-patent Document 6).
また、アロエ抽出物を有効成分とする毛乳頭活性化剤が報告されている（特許文献１）。しかしながら、特許文献１では、育毛に関して、毛乳頭における毛周期のうち、成長期を延長させる作用及び休止期から成長期への移行を促進する作用を見たものであり、育毛におけるVEGF産生促進作用を評価したものではない。 Moreover, the hair papilla activator which uses an aloe extract as an active ingredient has been reported (patent document 1). However, in Patent Document 1, regarding hair growth, among the hair cycles in the hair papilla, the effect of prolonging the growth phase and the effect of promoting the transition from the resting phase to the growth phase were observed. It is not something that was evaluated.
また、従来、例えばキダチアロエやアロエベラ等は、古くから医薬品や医薬部外品、化粧品等の外用組成物の有効成分として使用されている。これらのアロエ品種については、既に育毛分野での種々の研究が報告されている（非特許文献７〜９、及び特許文献２〜９）。 Conventionally, for example, Kidachi Aloe, Aloe Vera and the like have been used as active ingredients for external compositions such as pharmaceuticals, quasi drugs and cosmetics. For these aloe varieties, various studies in the field of hair growth have already been reported (Non-Patent Documents 7 to 9 and Patent Documents 2 to 9).
以上のことから、脱毛や薄毛といった症状の予防・改善のために、優れたVEGF産生促進剤、育毛剤及び発毛促進剤の開発が期待されている。また、VEGF産生促進効果を高めることで、血管新生が促され、毛細血管の生成も高められるので、育毛・発毛効果、創傷治癒効果、肌の血色改善効果、冷え改善効果、腸内の吸収促進効果等が期待できる。そして、育毛剤及び発毛促進剤に対するニーズは、ストレスの増加、女性の社会進出等に伴い増加傾向にある。 From the above, development of excellent VEGF production promoters, hair growth agents and hair growth promoters is expected for the prevention and improvement of symptoms such as hair loss and thinning hair. In addition, by enhancing the VEGF production promoting effect, angiogenesis is promoted and the formation of capillaries is also enhanced, so hair growth / hair growth effect, wound healing effect, skin color improvement effect, cooling improvement effect, absorption in the intestine A promotion effect can be expected. And the needs for hair growth agents and hair growth promoters are on the rise due to increased stress and the advancement of women into society.
また、脱毛の症例には、円形脱毛症等の成長期性（棍棒毛性）脱毛症、男性型脱毛症等の休止期性（萎縮毛性）脱毛症がある。脱毛の悩みを抱える対象者が、育毛剤を適切に用いることで、薄毛・抜け毛の進行を遅らせ、現状を維持できることから、対象者の生活の質（QOL）を向上させることができる。 In addition, examples of hair loss include growth phase (rod hair) alopecia such as alopecia areata and resting (atrophic) alopecia such as male pattern alopecia. Since the subject who has worries about hair loss can appropriately maintain the current state by delaying the progress of thinning and hair loss by appropriately using a hair-restoring agent, the quality of life (QOL) of the subject can be improved.
本発明は、ＶＥＧＦ産生促進剤を提供することを目的とする。 An object of this invention is to provide a VEGF production promoter.
また、本発明は、育毛及び／又は発毛促進剤を提供することを目的とする。 Moreover, an object of this invention is to provide the hair growth and / or hair growth promoter.
本発明者は、鋭意検討した結果、特定の種のアロエから抽出されたエキスが、VEGF産生促進効果をもたらすことを見出した。 As a result of intensive studies, the present inventor has found that an extract extracted from a specific species of aloe has an effect of promoting VEGF production.
本発明者は、更に、特定の種のアロエから抽出されたエキスが、育毛及び発毛促進効果をもたらすことを見出した。 The inventor has further found that an extract extracted from a specific species of aloe provides a hair growth and hair growth promoting effect.
すなわち、本発明は、以下の通りである。 That is, the present invention is as follows.
項１．アロエ・エルー、アロエ・カメロニー、アロエ・ケドンゲンシス、アロエ・フェロックス、アロエ・アフリカーナ、アロエ・アンドンゲンシス及びアロエ・トーメントーサ、並びにキダチアロエとアロエベラとの交配種からなる群より選択される少なくとも１種のアロエ植物体から抽出されたアロエエキスを有効成分とするＶＥＧＦ産生促進剤。 Item 1. At least one selected from the group consisting of Aloe Elue, Aloe Camellony, Aloe Kedongensis, Aloe Ferrox, Aloe Africana, Aloe Andungensis and Aloe Tormentosa, and a hybrid of Kidachi Aloe and Aloe Vera A VEGF production promoter comprising, as an active ingredient, an aloe extract extracted from an aloe plant body.
項２．前記アロエエキスが、前記アロエ植物体の水、エタノール及び１，３−ブチレングリコールよりなる群から選ばれる少なくとも１種の抽出溶媒で抽出されたものである、前記項１に記載のＶＥＧＦ産生促進剤。 Item 2. Item 2. The VEGF production promoter according to Item 1, wherein the aloe extract is extracted with at least one extraction solvent selected from the group consisting of water, ethanol and 1,3-butylene glycol of the aloe plant. .
項３．アロエ・エルー、アロエ・カメロニー、アロエ・ケドンゲンシス、アロエ・フェロックス、アロエ・アフリカーナ、アロエ・アンドンゲンシス及びアロエ・トーメントーサ、並びにキダチアロエとアロエベラとの交配種からなる群より選択される少なくとも１種のアロエ植物体から抽出されたアロエエキスを有効成分とする育毛及び／又は発毛促進剤。 Item 3. At least one selected from the group consisting of Aloe Elue, Aloe Camellony, Aloe Kedongensis, Aloe Ferrox, Aloe Africana, Aloe Andungensis and Aloe Tormentosa, and a hybrid of Kidachi Aloe and Aloe Vera A hair-growth and / or hair growth-promoting agent comprising, as an active ingredient, an aloe extract extracted from an aloe plant body.
項４．アロエエキスが、アロエ・エルー、アロエ・ケドンゲンシス及びアロエ・トーメントーサ、並びにキダチアロエとアロエベラとの交配種からなる群より選択される少なくとも１種のアロエ植物体から抽出されたアロエエキスである、前記項３に記載の育毛及び／又は発毛促進剤。 Item 4. The above-mentioned item, wherein the aloe extract is an aloe extract extracted from at least one aloe plant selected from the group consisting of aloe eru, aloe kedongensis and aloe tomentosa, and a hybrid of Kidachi aloe and aloe vera. 4. The hair growth and / or hair growth promoter according to 3.
項５．前記アロエエキスが、前記アロエ植物体の水、エタノール及び1,3-ブチレングリコールよりなる群から選ばれる少なくとも１種の抽出溶媒で抽出されたものである、請求項３又は４に記載の育毛及び／又は発毛促進剤。 Item 5. The hair growth according to claim 3 or 4, wherein the aloe extract is extracted with at least one extraction solvent selected from the group consisting of water, ethanol and 1,3-butylene glycol of the aloe plant. / Or hair growth promoter.
項６．アロエ・エルー、アロエ・カメロニー、アロエ・ケドンゲンシス、アロエ・フェロックス、アロエ・アフリカーナ、アロエ・アンドンゲンシス及びアロエ・トーメントーサ、並びにキダチアロエとアロエベラとの交配種からなる群より選択される少なくとも１種のアロエ植物体から抽出されたアロエエキスを有効成分とする細胞寿命延長剤。 Item 6. At least one selected from the group consisting of Aloe Elue, Aloe Camellony, Aloe Kedongensis, Aloe Ferrox, Aloe Africana, Aloe Andungensis and Aloe Tormentosa, and a hybrid of Kidachi Aloe and Aloe Vera A cell life extension agent comprising, as an active ingredient, an aloe extract extracted from an aloe plant.
本発明のVEGF産生促進剤は、アロエエキスが有するVEGF産生促進作用に基づいて、ヒト頭髪毛乳頭細胞等のVEGFの産生を促進することができる。 The VEGF production promoter of the present invention can promote the production of VEGF such as human hair hair papilla cells based on the VEGF production promoting action of aloe extract.
本発明のVEGF産生促進剤を用いると、VEGF産生量が高められ、血管新生が促され、毛細血管の生成も高められるので、脱毛の発生を防止し、発毛及び育毛を効果的に促進することが可能になる。また、創傷治癒効果、肌の血色改善効果、冷え改善効果、腸内の吸収促進効果等も期待できる。 When the VEGF production promoter of the present invention is used, the amount of VEGF production is increased, angiogenesis is promoted, and the formation of capillaries is also enhanced, thus preventing the occurrence of hair loss and effectively promoting hair growth and hair growth. It becomes possible. In addition, a wound healing effect, a skin color improvement effect, a cold improvement effect, an absorption promotion effect in the intestine, and the like can be expected.
また、本発明の育毛及び／又は発毛促進剤は、特定の種のアロエから抽出されたエキスを含有することにより、育毛及び／又は発毛を促進することができる。 Moreover, the hair growth and / or hair growth promoter of the present invention can promote hair growth and / or hair growth by containing an extract extracted from a specific species of aloe.
この様に、薄毛又は脱毛症に対して、本発明のVEGF産生促進剤、育毛及び／又は発毛促進剤を適切に用いることで、薄毛・抜け毛の進行を遅らせ、現状を維持することが期待できる。 As described above, the use of the VEGF production promoter, hair growth and / or hair growth promoter of the present invention for thinning hair or alopecia is expected to delay the progress of thinning / hair loss and maintain the current state. it can.
また、本発明の細胞寿命延長剤は、特定の種のアロエから抽出されたエキスを含有することにより、細胞の寿命を延長させることができる。 Moreover, the cell life extension agent of this invention can prolong the life of a cell by containing the extract extracted from the aloe of a specific kind.
以下、本発明について説明する。 The present invention will be described below.
本発明のVEGF産生促進剤は、有効成分として特定の種のアロエエキスを含有する。 The VEGF production promoter of the present invention contains a specific species of aloe extract as an active ingredient.
また、本発明の育毛及び／又は発毛促進剤は、有効成分として特定の種のアロエエキスを含有する。本発明でいう、育毛及び／又は発毛促進剤とは、発毛（毛を生やすこと）及び／又は育毛（毛を発育させたり、増やしたり、丈夫で太いものに育てること）を促進させるものである。 Further, the hair growth and / or hair growth promoter of the present invention contains a specific species of aloe extract as an active ingredient. The hair growth and / or hair growth-promoting agent referred to in the present invention is an agent that promotes hair growth (raising hair) and / or hair growth (growing or increasing hair, or growing it to be strong and thick). It is.
(1)アロエエキス
本発明のVEGF産生促進剤及び育毛及び／又は発毛促進剤に用いるアロエエキスを調製するためのアロエは、優れたVEGF産生促進作用、育毛促進作用及び／又は発毛促進作用を有することに加え、効果安全性、栽培の容易さ、又は日本薬局方でアロエとして使用が認められているという理由から、アロエ・エルー（学名：Aloe eru）、アロエ・カメロニー（又はアロエ・カメロン）（学名：Aloe cameronii）、アロエ・ケドンゲンシス（学名：Aloe kedongensis）、アロエ・フェロックス（学名：Aloe ferox）、アロエ・アフリカーナ（学名：Aloe africana）、アロエ・アンドンゲンシス（学名：Aloe andongensis）及びアロエ・トーメントーサ（学名：Aloe tomentosa）、並びにキダチアロエ（学名：Aloe arborescens）とアロエベラ（学名：Aloe vera）との交配種からなる群より選択される少なくとも１種である。
(1) Aloe extract Aloe for preparing an aloe extract for use in the VEGF production promoter and hair growth and / or hair growth promoter of the present invention has an excellent VEGF production promoting action, hair growth promoting action and / or hair growth promoting action. Aloe eru (Aloe eru), Aloe Camerony (or Aloe Cameron) due to its safety, effectiveness in cultivation, and the fact that it is approved for use as an aloe in the Japanese Pharmacopoeia ) (Scientific name: Aloe cameronii), Aloe kedongensis (scientific name: Aloe kedongensis), Aloe ferrox (scientific name: Aloe africana), Aloe africana (scientific name: Aloe andongensis) And Aloe tomentosa (scientific name: Aloe tomentosa) and crossbreds of Kidachi aloe (scientific name: Aloe arborescens) and aloe vera (scientific name: Aloe vera) Is at least one selected from the group consisting of
育毛及び／又は発毛促進剤に用いるアロエエキスとしては、前記アロエの中でも、特にアロエ・エルー（学名：Aloe eru）、アロエ・ケドンゲンシス（学名：Aloe kedongensis）及びアロエ・トーメントーサ（学名：Aloe tomentosa）、並びにキダチアロエ（学名：Aloe arborescens）とアロエベラ（学名：Aloe vera）との交配種からなる群より選択される少なくとも１種のアロエ植物体からの抽出物を好適に挙げることができる。 Among aloe extracts used as hair growth and / or hair growth promoters, aloe eru (scientific name: Aloe edong), aloe kedongensis (scientific name: Aloe kedongensis) and aloe tomentosa (scientific name: Aloe tomentosa) And an extract from at least one aloe plant selected from the group consisting of hybrids of Kidachi aloe (scientific name: Aloe arborescens) and aloe vera (scientific name: Aloe vera).
前記特定の種のアロエエキスは、植物由来であり、安全性が高く、日常的に摂取又は塗布し易いという利点を有する。 The specific species of aloe extract is derived from plants, has high safety, and has the advantage of being easy to ingest or apply on a daily basis.
本発明では、前記種から任意に選択した種間の交配種を使用することも可能であり、かかる交配種としては、アロエ・フェロックスとアロエ・アフリカーナとの交配種を挙げることができる。 In the present invention, it is also possible to use a hybrid between species arbitrarily selected from the above species, and examples of such a hybrid include a hybrid between Aloe Ferrox and Aloe Africana.
また、本発明で使用するアロエは、前記種の改良種を含むものである。 Moreover, the aloe used by this invention contains the improved kind of the said kind.
(2)アロエエキスの調製方法
本発明の有効成分であるアロエエキスの原料には、アロエ植物の全体をそのまま使用しても良い。またアロエの葉の外皮を使用しても良く、葉内部のゼリー質を使用しても良い。調製が容易という理由から、アロエ植物の全体を使用して、アロエエキスを調製することが好ましい。
(2) Preparation method of aloe extract As a raw material of the aloe extract which is an active ingredient of the present invention, the whole aloe plant may be used as it is. Moreover, the outer skin of an aloe may be used and the jelly quality inside a leaf may be used. For the reason that preparation is easy, it is preferable to prepare an aloe extract using the whole aloe plant.
抽出するアロエは、植物体（例えば、葉、茎、根等）の生の状態のもの（未乾燥物）、乾燥させたもの（乾燥物）、又は凍結したもの（凍結物）を用いることができる。また、アロエ植物体の未乾燥物、乾燥物又は凍結物を適切な大きさに細砕し粉末化したものを用いることもできる。 As the aloe to be extracted, a plant body (eg, leaf, stem, root, etc.) in a raw state (undried product), dried product (dried product), or frozen product (frozen product) may be used. it can. Further, an aloe plant body that has been pulverized into an appropriate size by pulverizing an undried product, a dried product, or a frozen product can also be used.
本発明に関するアロエのエキスを作製する方法としては、抽出工程及び分離工程を組み合わせる方法、上記方法に更に分画工程を組み合わせる方法等があげられるが、これらに限定されない。 Examples of the method for producing an aloe extract according to the present invention include, but are not limited to, a method of combining an extraction step and a separation step, a method of further combining a fractionation step with the above method, and the like.
抽出工程は、アロエ植物体から抽出溶媒を用いて、抽出物として必要な成分を取り出す工程であり、抽出方法や抽出条件は特に限定されない。 An extraction process is a process of taking out a component required as an extract from an aloe plant using an extraction solvent, and an extraction method and extraction conditions are not particularly limited.
抽出溶媒の種類は特に限定されないが、水、有機溶媒及びこれらの混合溶媒が挙げられる。上記の水としては、冷水、常温水、温水、熱水及び水蒸気等の全ての温度における水が挙げられ、また、殺菌処理、イオン交換処理、浸透圧調整又は緩衝化されていてもよい。有機溶媒としては、親水性有機溶媒が好ましく、例えば、炭素数１〜５の1価アルコール（エタノール、メタノール、プロパノール、イソプロパノール等）、炭素数2〜5の多価アルコール（グリセリン、イソプロピレングリコール、プロピレングリコール及び1,3-ブチレングリコール等）、エステル（酢酸メチル等）、ケトン（アセトン等）等を用いることができる。これらの親水性有機溶媒は、１種のみを用いてもよいし、２種以上を併用してもよい。本発明では、安全性及び有効成分の抽出効率の点から、水、エタノール、1,3-ブチレングリコールよりなる群から選ばれる少なくとも１種の抽出溶媒を用いることが好ましい。 Although the kind of extraction solvent is not specifically limited, Water, an organic solvent, and these mixed solvents are mentioned. Examples of the water include water at all temperatures such as cold water, room temperature water, hot water, hot water, and water vapor, and may be sterilized, ion exchanged, osmotic pressure adjusted or buffered. The organic solvent is preferably a hydrophilic organic solvent, for example, a monohydric alcohol having 1 to 5 carbon atoms (ethanol, methanol, propanol, isopropanol, etc.), a polyhydric alcohol having 2 to 5 carbon atoms (glycerin, isopropylene glycol, Propylene glycol and 1,3-butylene glycol), esters (such as methyl acetate), ketones (such as acetone), and the like can be used. These hydrophilic organic solvents may use only 1 type and may use 2 or more types together. In the present invention, it is preferable to use at least one extraction solvent selected from the group consisting of water, ethanol, and 1,3-butylene glycol from the viewpoint of safety and extraction efficiency of active ingredients.
抽出溶媒として水及び1,3-ブチレングリコールの混合液を用いる場合は、混合液中の1,3-ブチレングリコールの含有率は、0.1〜70重量%程度が好ましく、5〜60重量%程度がより好ましく、10〜50重量%程度が更に好ましい。 When a mixed solution of water and 1,3-butylene glycol is used as the extraction solvent, the content of 1,3-butylene glycol in the mixed solution is preferably about 0.1 to 70% by weight, and about 5 to 60% by weight. More preferred is about 10 to 50% by weight.
抽出溶媒として、水及びエタノールの混合液を用いる場合は、混合液中のエタノールの含有率は、0.1〜99.5重量%程度が好ましく、5〜95重量%程度がより好ましく、50〜90重量%程度が更に好ましく、60〜80重量%程度が最も好ましい。 When a mixed solution of water and ethanol is used as the extraction solvent, the ethanol content in the mixed solution is preferably about 0.1 to 99.5% by weight, more preferably about 5 to 95% by weight, and about 50 to 90% by weight. Is more preferable, and about 60 to 80% by weight is most preferable.
抽出手法としては、浸漬抽出、攪拌抽出、還流抽出、振とう抽出及び超音波抽出があげられ、抽出条件としては、室温抽出、加熱抽出（加温抽出ともいう）、加圧抽出、超臨界抽出等があげられるが、好ましくは、室温又は加熱抽出である。抽出時間は特に限定されない。また、ｐＨ調整してもよい。上記抽出操作は、１回でもよく、抽出操作を行った後に得られる抽出残渣を再度抽出することを複数回数繰り返すことにより行ってもよい。更に、抽出工程の前後に、必要に応じて濾過等の処理を行ってもよい。 Examples of extraction methods include immersion extraction, stirring extraction, reflux extraction, shaking extraction, and ultrasonic extraction. Extraction conditions include room temperature extraction, heat extraction (also called warm extraction), pressure extraction, and supercritical extraction. Among them, room temperature or heating extraction is preferable. The extraction time is not particularly limited. Moreover, you may adjust pH. The extraction operation may be performed once, or may be performed by repeating extraction of the extraction residue obtained after the extraction operation a plurality of times. Furthermore, before and after the extraction step, a treatment such as filtration may be performed as necessary.
分離工程は、上記で得られた抽出物から、抽出残渣である不溶物と抽出液とを分離する固液方法であり、例えば、遠心分離、フィルタプレス、濾過（加圧、常圧）、クロマトグラフィー等の吸着剤・吸収剤を用いた抽出分離等による方法が挙げられる。抽出液から分取された抽出物はそのまま用いてもよく、更に分画等により精製してもよい。 The separation step is a solid-liquid method for separating the insoluble matter that is the extraction residue and the extract from the extract obtained above. For example, centrifugation, filter press, filtration (pressurization, normal pressure), chromatography Examples thereof include a method by extraction separation using an adsorbent / absorbent such as graphy. The extract collected from the extract may be used as it is, or further purified by fractionation or the like.
分画工程は、上記で得られた抽出物から必要な成分を分画して精製及び濃縮する方法である。分画工程に用いられる方法としては、担体として活性炭、陰イオン交換樹脂、陽イオン交換樹脂、シリカゲル、芳香族化合物を吸着するポリスチレン系の樹脂等を用いるクロマトグラフィー、透析、分子ふるい、減圧濃縮、凍結乾燥等の方法があげられるがこれらに限定されない。更に、本工程後に、必要に応じて遠心分離等により上清を回収する工程を行ってもよい。 The fractionation step is a method of fractionating and purifying and concentrating necessary components from the extract obtained above. As a method used in the fractionation step, activated carbon, anion exchange resin, cation exchange resin, silica gel, chromatography using a polystyrene-based resin that adsorbs an aromatic compound, dialysis, molecular sieve, vacuum concentration, Although methods, such as freeze-drying, are mentioned, it is not limited to these. Furthermore, you may perform the process of collect | recovering supernatants by centrifugation etc. as needed after this process.
なお、上記各工程の前後に、必要に応じて濾過等の処理を行ってもよい。濾過には、ガーゼや濾過フィルター、市販の濾過器等を用いることができる。また、必要に応じて、滅菌処理等を施すことができる。 In addition, you may perform processes, such as filtration, before and after each said process as needed. A gauze, a filtration filter, a commercially available filter, etc. can be used for filtration. Moreover, a sterilization process etc. can be given as needed.
上記方法により、本発明のアロエエキスを得ることができる。得られたアロエエキスは、そのままの液状形態を有していてもよいが、噴霧乾燥、真空乾燥、凍結乾燥等の乾燥工程により粉末化することもできる。 The aloe extract of the present invention can be obtained by the above method. The obtained aloe extract may have a liquid form as it is, but can also be pulverized by a drying process such as spray drying, vacuum drying, freeze drying and the like.
(3)ＶＥＧＦ産生促進剤
本発明のVEGF（血管内皮増殖因子、vascular endothelial growth factor）産生促進剤は、前記アロエエキスを有効成分として含有するものである。
(3) VEGF production promoter The VEGF (vascular endothelial growth factor) production promoter of the present invention contains the aloe extract as an active ingredient.
本発明のVEGF産生促進剤におけるアロエエキスの配合割合は、本発明の効果が発揮されることを限度として制限されないが、例えば、VEGF産生促進剤中に、アロエエキスが100重量%含まれていてもよく、好ましくは10〜90重量%程度、より好ましくは20〜80重量%程度が挙げられる。 The blending ratio of the aloe extract in the VEGF production promoter of the present invention is not limited as long as the effect of the present invention is exerted. For example, the VEGF production promoter contains 100% by weight of aloe extract. Preferably, it is about 10 to 90% by weight, more preferably about 20 to 80% by weight.
本発明のVEGF産生促進剤（医薬品の形態を含む）は、その形態は特に制限されず、非経口投与形態及び経口投与形態のいずれもが含まれる。 The form of the VEGF production promoter (including pharmaceutical forms) of the present invention is not particularly limited, and includes both parenteral and oral dosage forms.
非経口投与形態としては、注射剤、点滴剤、経皮吸収剤等が挙げられる。経皮吸収剤とする場合、軟膏剤、ゲル剤、ペースト剤、クリーム剤、ローション剤、噴霧剤、溶液剤、懸濁液剤等の外用製剤とすることができる。また、注射剤とする場合、局所注入、腹腔内投与、選択的静脈注入、静脈注射、皮下注射、臓器灌流液注入等の方法を選択することができる。 Examples of parenteral dosage forms include injections, infusions, transdermal absorption agents, and the like. When it is used as a transdermal absorption agent, it can be made into external preparations such as ointments, gels, pastes, creams, lotions, sprays, solutions and suspensions. In the case of an injection, methods such as local injection, intraperitoneal administration, selective intravenous injection, intravenous injection, subcutaneous injection, and organ perfusate injection can be selected.
本発明のVEGF産生促進剤を外用製剤として使用する場合、基剤として、低級アルコール及び水を使用することができる。低級アルコールとしては、メタノール；エタノール；n-プロピルアルコール、イソプロピルアルコール；1,3-ブチルアルコール、sec-ブチルアルコール、イソブチルアルコール、tert-ブチルアルコール；ベンジルアルコール等の炭素数１〜７のアルコールを例示することができる。 When the VEGF production promoter of the present invention is used as an external preparation, lower alcohol and water can be used as a base. Examples of lower alcohols include methanol; ethanol; n-propyl alcohol, isopropyl alcohol; 1,3-butyl alcohol, sec-butyl alcohol, isobutyl alcohol, tert-butyl alcohol; benzyl alcohol and other alcohols having 1 to 7 carbon atoms. can do.
外用製剤として使用する場合、肌への刺激性軽減という理由から、そのｐＨが４〜８の範囲にあることが好ましい。ｐＨ調整は、塩基性物質又は酸性物質を用いて行うことができる。塩基性物質としては、水酸化ナトリウムや水酸化カリウム等の無機塩基；トリエタノールアミンやジイソプロパノールアミン等の有機アミン類；アルギニン、リジン、オルニチン等の塩基性アミノ酸等を挙げることができる。また、酸性物質としては、塩酸、硝酸、メタスルホン酸、硫酸、p-トルエンスルホン酸、リン酸、クエン酸、リンゴ酸、酒石酸、コハク酸等の無機酸及び有機酸を挙げることができる。 When used as a preparation for external use, the pH is preferably in the range of 4 to 8 for the reason of reducing irritation to the skin. The pH adjustment can be performed using a basic substance or an acidic substance. Examples of the basic substance include inorganic bases such as sodium hydroxide and potassium hydroxide; organic amines such as triethanolamine and diisopropanolamine; basic amino acids such as arginine, lysine and ornithine. Examples of the acidic substance include inorganic acids and organic acids such as hydrochloric acid, nitric acid, metasulfonic acid, sulfuric acid, p-toluenesulfonic acid, phosphoric acid, citric acid, malic acid, tartaric acid, and succinic acid.
外用製剤として使用する場合、他成分として薬効補助剤を配合することも可能である。薬効補助剤としては、カンフル、テレピン油、ハッカ油、メントール及びその誘導体、ユーカリ油、乳酸メンチル等の清涼化剤；ノナン酸バニリルアミド、カプサイシン等の局所刺激剤；グリチルリチン酸等の抗炎症剤；ジフェニルイミダゾール、ジフェンヒドラミン及びその塩、マレイン酸クロルフェニラミン等の抗ヒスタミン剤；酢酸トコフェロール、ニコチン酸ベンジル等の血行促進剤；アルニカチンキ、オウバクエキス、サンシシエキス、セイヨウトチノキエキス、ロートエキス、ベラドンナエキス、トウキエキス、シコンエキス、サンショウエキス、トウガラシエキス等の生薬等が挙げられる。上記の成分の他、適当な併用可能な活性成分、防腐剤、保存剤、酸化防止剤、安定化剤等の通常の皮膚外用剤に使用される添加剤を適宜用いることができる。 When used as a preparation for external use, a medicinal aid can be blended as another component. Medicinal aids include: camphor, turpentine oil, peppermint oil, menthol and its derivatives, eucalyptus oil, lactic acid menthyl, etc .; local stimulants such as nonanoic acid vanillylamide, capsaicin; anti-inflammatory agents such as glycyrrhizic acid; diphenyl Antihistamines such as imidazole, diphenhydramine and salts thereof, chlorpheniramine maleate; blood circulation promoters such as tocopherol acetate and benzyl nicotinate; And herbal medicines such as salamander extract and pepper extract. In addition to the above-mentioned components, suitable additives that can be used in combination with active ingredients such as preservatives, preservatives, preservatives, antioxidants, stabilizers and the like, which are used in normal external preparations for skin, can be used as appropriate.
本発明のVEGF産生促進剤は、外用製剤として調製され、局所的に外用投与することができる。本発明のVEGF産生促進剤の投与量は、対象者の年齢や性別、脱毛症状の程度等によって異なり、一律に規定することはできないが、VEGF産生を促進できれば良い。VEGF産生促進剤の投与量は、アロエエキスの乾燥重量に換算して、成人１日用量として、好ましくは0.00001〜1g、より好ましくは0.0001〜0.1g程度となる量であることが望ましい。 The VEGF production promoter of the present invention is prepared as an external preparation and can be locally administered externally. The dose of the VEGF production promoter of the present invention varies depending on the age and sex of the subject, the degree of hair loss symptoms, etc., and cannot be defined uniformly, but it is only required to promote VEGF production. The dose of the VEGF production promoter is preferably an amount that is preferably about 0.00001 to 1 g, more preferably about 0.0001 to 0.1 g as an adult daily dose in terms of the dry weight of the aloe extract.
経口投与形態としては、慣用の形態がいずれも含まれ、特に制限されない。通常、液剤（シロップ等を含む）等の液状製剤（懸濁剤含む）；及び錠剤、丸剤、散剤、細粒剤、顆粒剤、カプセル剤（ソフトカプセルを含む）等の固形製剤が含まれる。 The oral dosage form includes any conventional form and is not particularly limited. Usually, liquid preparations (including suspensions) such as liquids (including syrups); and solid preparations such as tablets, pills, powders, fine granules, granules, and capsules (including soft capsules).
本発明のVEGF産生促進剤は、経口投与可能な形態とする場合、製剤には薬剤的に許容できる種々の担体を加えることができる。例えば、賦形剤、結合剤、崩壊剤、滑沢剤、着香剤、着色剤、甘味剤、矯味剤、溶解補助剤、懸濁化剤、乳化剤、コーティング剤、抗酸化剤等を含むことができる。 When the VEGF production promoter of the present invention is in a form that can be administered orally, various pharmaceutically acceptable carriers can be added to the preparation. For example, including excipients, binders, disintegrants, lubricants, flavoring agents, coloring agents, sweeteners, corrigents, solubilizers, suspending agents, emulsifiers, coating agents, antioxidants, etc. Can do.
本発明のVEGF産生促進剤を、経口投与形態とする場合、摂取量は、VEGFの産生を促進できる量であれば良い。VEGF産生促進剤の投与量は、アロエエキスの乾燥重量に換算して、成人１日用量として、好ましくは0.0006〜6g（0.01〜100mg／kg体重）、より好ましくは0.006〜6g（0.1〜100mg／kg体重）を使用する。勿論個別的に、投与されるヒトの年齢、体重、症状、投与経路、投与期間及び治療経過等に応じて変化させることもできる。１日あたりの量を数回に分けて投与することもできる。 When the VEGF production promoter of the present invention is used as an oral administration form, the intake may be an amount that can promote the production of VEGF. The dose of the VEGF production promoter is preferably 0.0006 to 6 g (0.01 to 100 mg / kg body weight), more preferably 0.006 to 6 g (0.1 to 100 mg / kg) as the daily dose for adults in terms of the dry weight of aloe extract. kg body weight). Of course, it can be changed individually according to the age, weight, symptom, administration route, administration period, treatment course, etc. of the administered human. The daily dose can be administered in several divided doses.
また、本発明のVEGF産生促進剤は、一成分として食品に配合させることもできる。この場合は、本発明のVEGF産生促進剤を、例えば、食品添加物の形態とすることもできる。また医薬品又は医薬部外品の形態に調製して皮膚の脱毛改善用に使用したり、育毛及び／又は発毛促進用の医薬品又は医薬部外品に適用したりすることも可能である。 Moreover, the VEGF production promoter of this invention can also be mix | blended with foodstuffs as one component. In this case, the VEGF production promoter of the present invention can be in the form of a food additive, for example. It can also be prepared in the form of pharmaceuticals or quasi-drugs and used for improving skin hair loss, or applied to pharmaceuticals or quasi-drugs for promoting hair growth and / or hair growth.
VEGF産生促進剤を配合する食品として、好ましくは、保健機能食品（栄養機能食品及び特定保健用食品）、所謂健康食品、栄養補助食品又は特別用途食品（病者用食品等）等を挙げることができる。形態としては、例えば、散剤、錠剤、カプセル剤、シロップ剤、ゼリー等の形態のものが挙げられる。水を抽出溶媒として用いて得られるアロエエキスはそのまま飲用することができるので、該抽出液自体、又はその濃縮液や希釈液を飲料形態の食品としてもよい。 The food containing the VEGF production promoter preferably includes health functional foods (nutrient functional foods and foods for specified health use), so-called health foods, nutritional supplements or special use foods (foods for the sick, etc.). it can. Examples of forms include powders, tablets, capsules, syrups, jelly, and the like. Since the aloe extract obtained by using water as an extraction solvent can be drunk as it is, the extract itself or a concentrated solution or a diluted solution thereof may be used as a beverage-type food.
本発明のVEGF産生促進剤は、非経口投与形態又は経口投与形態である他の育毛剤と組み合わせて使用してもよく、これによって育毛効果をより顕著に発現することもある。 The VEGF production promoter of the present invention may be used in combination with other hair growth agents that are in a parenteral administration form or an oral administration form, and thereby, the hair growth effect may be more remarkably exhibited.
本発明は、アロエエキスを有効成分とするので、後述する実験データで示される通り、VEGFの産生を促進することができる。 Since the present invention uses aloe extract as an active ingredient, the production of VEGF can be promoted as shown in the experimental data described later.
(4)アロエエキスのVEGF産生促進の評価方法
アロエエキスのVEGF産生促進作用は、ヒト頭髪毛乳頭細胞（HFDPC）等の哺乳類の毛乳頭細胞を使用して、評価することができる。
(4) Evaluation Method for Promoting VEGF Production by Aloe Extract The VEGF production promoting action of aloe extract can be evaluated using mammalian hair papilla cells such as human hair papilla cells (HFDPC).
毛乳頭細胞が産生するVEGF量の測定
以下の手順で、毛乳頭細胞によって培養液中に分泌されたVEGFをELISAにより測定する。
Measurement of VEGF amount produced by dermal papilla cells VEGF secreted into the culture medium by dermal papilla cells is measured by ELISA according to the following procedure.
1.毛乳頭細胞を、専用の毛乳頭細胞増殖培地（PCGM、東洋紡績（株）より購入）で調製し、植え継ぎを行い、37℃の条件で一晩培養する。次に細胞の生育状況を確認し、培養液全量を交換する。 1. Prepare dermal papilla cells in a dedicated dermal papilla cell growth medium (PCGM, purchased from Toyobo Co., Ltd.), inoculate and culture overnight at 37 ° C. Next, the growth state of the cells is confirmed, and the whole culture solution is exchanged.
2.培養液中に被検物質（アロエエキス）を添加してインキュベートを開始する。 2. Add the test substance (aloe extract) to the culture medium and start the incubation.
この際、VEGFの産生を促進するモデル薬剤として、ミノキシジル（Minoxidil）を使用してもよい。 At this time, minoxidil may be used as a model drug for promoting VEGF production.
3.培養液をサンプリングし、市販のHuman VEGF ELISAキット（R&D SYSTEMS:DY293B）を用いて、培養液中のVEGF濃度を測定する。 3. The culture solution is sampled and the VEGF concentration in the culture solution is measured using a commercially available Human VEGF ELISA kit (R & D SYSTEMS: DY293B).
陰性対照として、被検物質の代わりに、使用する抽出溶媒のみを添加した培養液を用いる。この陰性対照に対して、被検物質を添加したサンプル中のVEGF濃度が高いとき、そのサンプルはVEGF産生促進作用が有ると判断できる。 As a negative control, a culture solution containing only the extraction solvent to be used is used instead of the test substance. In contrast to this negative control, when the VEGF concentration in the sample to which the test substance is added is high, it can be determined that the sample has an effect of promoting VEGF production.
(5)育毛及び／又は発毛促進剤
前記アロエエキスによれば、VEGF産生量が高められる結果、血管新生が促され、毛細血管の生成も高められるので、育毛効果及び発毛効果を発揮することが出来る。
(5) Hair growth and / or hair growth promoter According to the above aloe extract, VEGF production is increased, and as a result, angiogenesis is promoted and capillaries are also increased. I can do it.
よって、本発明は、前記アロエエキスを有効成分とする育毛及び／又は発毛促進剤を提供する。本発明の育毛及び／又は発毛促進剤を使用することで、育毛及び／又は発毛を促進することができる。 Therefore, this invention provides the hair growth and / or hair growth promoter which uses the said aloe extract as an active ingredient. By using the hair growth and / or hair growth promoter of the present invention, hair growth and / or hair growth can be promoted.
本発明の育毛及び／又は発毛促進剤は、アロエ・エルー、アロエ・カメロニー、アロエ・ケドンゲンシス、アロエ・フェロックス、アロエ・アフリカーナ、アロエ・アンドンゲンシス及びアロエ・トーメントーサ、並びにキダチアロエとアロエベラとの交配種からなる群より選択される少なくとも１種のアロエ植物体から抽出されたアロエエキスを有効成分とすることが好ましい。 The hair-growth and / or hair growth-promoting agent of the present invention includes Aloe Elue, Aloe Camellony, Aloe Kedongensis, Aloe Ferrox, Aloe Africana, Aloe Andogensis and Aloe Tormentosa, and Kidachi Aloe and Aloe Vera. It is preferable to use as an active ingredient an aloe extract extracted from at least one aloe plant selected from the group consisting of:
本発明の育毛及び／又は発毛促進剤におけるアロエエキスの配合割合は、前記VEGF産生促進剤の項で記載した配合割合を適用することができる。 The blending ratio of the aloe extract in the hair growth and / or hair growth promoter of the present invention can be the blending ratio described in the section of the VEGF production promoter.
また、本発明の育毛及び／又は発毛促進剤の形態も、前記VEGF産生促進剤の項で記載した非経口投与形態（外用製剤等）及び経口投与形態のいずれも適用することができる。 In addition, the form of the hair growth and / or hair growth promoter of the present invention can be applied to any of the parenteral dosage forms (external preparations, etc.) and oral dosage forms described in the section of the VEGF production promoter.
また、本発明の育毛及び／又は発毛促進剤は、前記VEGF産生促進剤の項で記載した投与量又は摂取量を適用することができる。 The hair growth and / or hair growth promoting agent of the present invention can be applied to the dosage or intake described in the section of the VEGF production promoter.
また、本発明の育毛及び／又は発毛促進剤は、前記VEGF産生促進剤の項で記載したように、一成分として食品（保健機能食品等）に配合させることもできる。本発明の育毛及び／又は発毛促進剤を、例えば、食品添加物の形態とすること等も可能である。 Moreover, the hair growth and / or hair growth promoter of the present invention can be added to foods (health functional foods, etc.) as one component, as described in the section of the VEGF production promoter. The hair growth and / or hair growth promoter of the present invention can be in the form of, for example, a food additive.
本発明の育毛及び／又は発毛促進剤は、前記アロエエキスの中でも、優れた育毛効果及び発毛効果が得られるという理由から、アロエ・エルー、アロエ・ケドンゲンシス、アロエ・トーメントーサ及びキダチアロエとアロエベラとの交配種からなる群より選択される少なくとも１種のアロエ植物体から抽出されたアロエエキスを有効成分とすることが好ましい。 The hair-growth and / or hair growth-promoting agent of the present invention is the aloe extract, because of the excellent hair-growth effect and hair-growth effect. It is preferable to use as an active ingredient an aloe extract extracted from at least one kind of aloe plant selected from the group consisting of the hybrids.
薄毛又は脱毛症に対して、本発明の育毛及び／又は発毛促進剤を適切に用いることで、薄毛・抜け毛の進行を遅らせ、現状を維持することが期待できる。 By appropriately using the hair growth and / or hair growth promoter of the present invention against thinning hair or alopecia, it is expected that the progress of thinning and hair loss is delayed and the current state is maintained.
本発明の本発明の育毛及び／又は発毛促進剤を、脱毛の防止及び育毛を目的とする外用剤である、育毛剤（養毛剤）の医薬品又は医薬部外品への適用が可能である。医薬品及び医薬部外品の剤型として、液剤及びエアゾール剤の剤型等への応用が可能である。 The hair-growth and / or hair growth-promoting agent of the present invention can be applied to pharmaceuticals or quasi-drugs of hair-growth agents (hair-growth agents), which are external preparations for the purpose of preventing hair loss and hair growth. As dosage forms of pharmaceuticals and quasi drugs, it can be applied to liquid dosage forms and aerosol dosage forms.
本発明の育毛及び／又は発毛促進剤を、医薬品又は医薬部外品として使用することで、育毛、薄毛・かゆみ・脱毛の予防、毛生促進、発毛促進、ふけ・病後・産後の脱毛の予防、及び養毛の効果を得ることができる。 By using the hair growth and / or hair growth promoter of the present invention as a pharmaceutical product or quasi-drug, hair growth, prevention of hair thinning / itching / hair loss, hair growth promotion, hair growth promotion, dandruff / post-disease / postpartum hair loss Prevention and hair nourishing effects can be obtained.
本発明の育毛及び／又は発毛促進剤を、薬用化粧品への適用が可能である。薬用化粧品として、シャンプー及びリンスへの応用が可能である。 The hair growth and / or hair growth promoting agent of the present invention can be applied to medicinal cosmetics. As a medicated cosmetic, it can be applied to shampoos and rinses.
本発明の育毛及び／又は発毛促進剤を、薬用化粧品のシャンプーとして使用することで、毛髪をすこやかに保つ、又は毛髪をしなやかにする効果を得ることができる。また、本発明の育毛及び／又は発毛促進剤を、薬用化粧品のリンスとして使用することで、裂毛・切毛・枝毛を防ぐ、毛髪をすこやかに保つ、又は毛髪をしなやかにする効果を得ることができる。 By using the hair growth and / or hair growth promoter of the present invention as a shampoo for medicinal cosmetics, it is possible to obtain an effect of keeping the hair smooth or supple. In addition, by using the hair growth and / or hair growth promoter of the present invention as a rinse for medicinal cosmetics, the effect of preventing fissures, cuts, split ends, keeping hair smooth, or supple hair is obtained. be able to.
本発明の育毛及び／又は発毛促進剤を、化粧品（化粧料）への適用が可能である。化粧品としては、化粧水、ローション等の乳液、クリーム、ジェル等が好ましい。化粧品の剤型として、固形化粧料、液状化粧料、練状化粧料、粉状化粧料、ゼリー状化粧料、ジェル状化粧料、ペースト状化粧料、スプレー型化粧料等の剤型への応用が可能である。 The hair growth and / or hair growth promoter of the present invention can be applied to cosmetics (cosmetics). As cosmetics, lotion such as lotion, lotion, cream, gel and the like are preferable. As cosmetic dosage forms, application to solid cosmetics, liquid cosmetics, paste-like cosmetics, powdery cosmetics, jelly-like cosmetics, gel-like cosmetics, paste-like cosmetics, spray-type cosmetics, etc. Is possible.
本発明の育毛及び／又は発毛促進剤を、化粧料として使用することで、（1）頭皮、毛髪をすこやかに保つ、（2）毛髪にはり、こしを与える、（3）頭皮、毛髪にうるおいを与える、（4）頭皮、毛髪のうるおいを保つ、（5）毛髪をしなやかにする、（6）毛髪のつやを保つ、（7）毛髪につやを与える、（8）フケ、カユミがとれる、（9）フケ、カユミを抑える、（10）毛髪の水分、油分を補い保つ、（11）裂毛、切毛、枝毛を防ぐ、等の効果を得ることができる。 By using the hair-growth and / or hair growth-promoting agent of the present invention as a cosmetic, (1) keep the scalp and hair healthy, (2) give the hair a scalp, and (3) apply it to the scalp and hair Moisturize, (4) Keep the scalp and hair moist, (5) Make the hair supple, (6) Keep the hair shiny, (7) Give the hair shine, (8) Dandruff, Kayumi , (9) Suppresses dandruff and damaging, (10) supplements and keeps moisture and oil in hair, (11) prevents cracks, cuts, split ends, and the like.
(6)アロエエキスの育毛及び発毛促進の評価方法
アロエエキスの育毛及び発毛促進作用は、直接的には、マウス等の哺乳類を用いた発毛試験により、評価することができる。また、間接的には、線虫寿命延長作用に基づいて評価することも出来る。その測定方法については、実施例に記載する。
(6) Evaluation Method for Hair Growth and Hair Growth Promotion of Aloe Extract The hair growth and hair growth promoting action of the aloe extract can be directly evaluated by a hair growth test using a mammal such as a mouse. Moreover, indirectly, it can also evaluate based on a nematode lifetime extension effect | action. About the measuring method, it describes in an Example.
マウス育毛及び発毛の試験
以下の手順で、マウスの皮膚に対する育毛及び発毛促進効果を評価する。
Mouse hair growth and hair growth test The following procedures evaluate hair growth and hair growth promoting effects on mouse skin.
1.被験物質（アロエエキス）をエタノール水溶液（50重量%程度）に溶解し、試験サンプルとする（例：固形分3重量%）。陰性対照として、エタノール水溶液を用いる。 1. Dissolve the test substance (aloe extract) in an aqueous ethanol solution (about 50% by weight) to give a test sample (eg, 3% by weight solids). As a negative control, an aqueous ethanol solution is used.
2.除毛したマウスの背部皮膚に、1日1回、数日間、連日で、試験サンプルを塗布投与する。 2. Apply and administer the test sample once a day for several days on the dorsal skin of the mouse after hair removal.
3.投与開始日（投与1日）〜投与最終日の投与期間で、除毛部位内を観察する。 3. The inside of the hair removal site is observed during the administration period from the administration start date (administration day 1) to the final administration date.
陰性対照として、被検物質の代わりに、50重量%エタノール水溶液等を用いる。この陰性対照群に対して、被検物質のエタノール水溶液（試験サンプル）群で発毛及び育毛が認められたとき、その試験サンプルは育毛及び発毛促進作用が有ると判断できる。 As a negative control, a 50 wt% aqueous ethanol solution or the like is used instead of the test substance. In contrast to this negative control group, when hair growth and hair growth are observed in the ethanol aqueous solution (test sample) group of the test substance, it can be determined that the test sample has a hair growth and hair growth promoting action.
(7)細胞寿命延長剤
前記アロエエキスによれば、後述の線虫寿命延長試験により、細胞の寿命に対する延長作用を示すことが明らかとなった。
(7) Cell Life Extension Agent According to the aloe extract described above, it was revealed by the nematode life extension test described later that the cell life extension action was exhibited.
よって、本発明は、前記アロエエキスを有効成分とする細胞寿命延長剤を提供する。 Therefore, the present invention provides a cell life extension agent comprising the aloe extract as an active ingredient.
本発明の細胞寿命延長剤は、アロエ・エルー、アロエ・カメロニー、アロエ・ケドンゲンシス、アロエ・フェロックス、アロエ・アフリカーナ、アロエ・アンドンゲンシス及びアロエ・トーメントーサ、並びにキダチアロエとアロエベラとの交配種からなる群より選択される少なくとも１種のアロエ植物体から抽出されたアロエエキスを有効成分とすることが好ましい。 The cell life extension agent of the present invention includes Aloe Elue, Aloe Camellony, Aloe Kedongensis, Aloe Ferrox, Aloe Africana, Aloe Andogensis and Aloe Tormentosa, and a cross between Kidachi aloe and Aloe vera. It is preferable to use as an active ingredient an aloe extract extracted from at least one aloe plant selected from the group consisting of:
本発明の細胞寿命延長剤におけるアロエエキスの配合割合は、前記VEGF産生促進剤の項で記載した配合割合を適用することができる。 As the compounding ratio of the aloe extract in the cell life extending agent of the present invention, the compounding ratio described in the section of the VEGF production promoter can be applied.
また、本発明の細胞寿命延長剤の形態も、前記VEGF産生促進剤の項で記載した非経口投与形態（外用製剤等）及び経口投与形態のいずれも適用することができる。 In addition, as the form of the cell life extension agent of the present invention, any of a parenteral administration form (external preparation, etc.) and an oral administration form described in the section of the VEGF production promoter can be applied.
また、本発明の細胞寿命延長剤は、前記VEGF産生促進剤の項で記載した投与量又は摂取量を適用することができる。 Moreover, the dosage amount or ingestion amount described in the section of the VEGF production promoter can be applied to the cell life extension agent of the present invention.
また、本発明の細胞寿命延長剤は、前記VEGF産生促進剤の項で記載したように、一成分として食品（保健機能食品等）に配合させることもできる。本発明の細胞寿命延長剤を、例えば、食品添加物の形態とすること等も可能である。 Moreover, the cell life extension agent of this invention can also be mix | blended with foodstuffs (health functional food etc.) as one component, as described in the term of the said VEGF production promoter. The cell life extension agent of the present invention can be, for example, in the form of a food additive.
本発明の細胞寿命延長剤は、前記アロエエキスの中でも、優れた細胞寿命の延長作用が得られるという理由から、アロエ・エルー、アロエ・ケドンゲンシス、アロエ・トーメントーサ及びキダチアロエとアロエベラとの交配種からなる群より選択される少なくとも１種のアロエ植物体から抽出されたアロエエキスを有効成分とすることが好ましい。 The cell life extension agent of the present invention is, among the aloe extracts, from the reason that an excellent cell life extension action can be obtained, from Aloe Elue, Aloe Kedongensis, Aloe Tormentosa, and a cross between Aloe vera and Aloe Vera. It is preferable to use as an active ingredient an aloe extract extracted from at least one aloe plant selected from the group consisting of:
以下、実施例により本発明をさらに詳細に説明するが、本発明は実施例によって限定されるものではない。 EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited by an Example.
実験例１ アロエエキスによるVEGF産生促進作用
(1)アロエエキスの調製
各種アロエ（生の植物体として1kg）を細かく刻んだ後に乾燥し、その乾燥物全量（30〜70g）に、8倍量のエタノール水溶液（90重量%エタノール）を加えて50℃で5時間攪拌し、ろ過、濃縮、凍結乾燥の工程を経てエキス（抽出物）を得た（表１）。
Experimental Example 1 VEGF production promotion effect by aloe extract
(1) Preparation of aloe extract Various aloe (1kg as a raw plant) is finely chopped and dried, and 8 times the amount of ethanol aqueous solution (90 wt% ethanol) is added to the total amount of the dried product (30-70g) The mixture was stirred at 50 ° C. for 5 hours, and an extract (extract) was obtained through the steps of filtration, concentration, and lyophilization (Table 1).
参考例として、キダチアロエ及びアロエベラ（乾燥物の植物体として10g）を細かく刻み、その粉砕物に、10倍量の水、エタノール又は1,3-ブチレングリコール（100mL）を加えて、２日間静置し、エキス（抽出液）を調製した（表２）。 As a reference example, Kidachi aloe vera and aloe vera (10 g as a dried plant) are finely chopped, and 10 times the amount of water, ethanol or 1,3-butylene glycol (100 mL) is added to the pulverized product, and left for 2 days. Then, an extract (extract) was prepared (Table 2).
比較例として、アロエ以外の植物体のエキスも同様にして得た（表２）。 As a comparative example, plant extracts other than aloe were obtained in the same manner (Table 2).
アロエエキスを含む各エキスの詳細を表１に示した。表中、EtOHはエタノールを示し、BGは1,3-ブチレングリコールを示す。 Details of each extract including the aloe extract are shown in Table 1. In the table, EtOH represents ethanol, and BG represents 1,3-butylene glycol.
(2)VEGF産生作用の評価
1.毛乳頭細胞が産生したVEGF量の測定
上記調製した各サンプルのVEGF産生量を、ヒト頭髪毛乳頭細胞（HFDPC）（東洋紡績株式会社製）を使用して、評価した。
(2) Evaluation of VEGF production
1. Measurement of the amount of VEGF produced by hair papilla cells The amount of VEGF produced by each sample prepared above was evaluated using human hair hair papilla cells (HFDPC) (manufactured by Toyobo Co., Ltd.).
1-1.専用の増殖培地（PCGM）とT-75フラスコ（collagen-coated）を用いて、37℃、CO2インキュベーター（5%）内で細胞を培養した。 1-1. Cells were cultured in a CO2 incubator (5%) at 37 ° C. using a dedicated growth medium (PCGM) and a T-75 flask (collagen-coated).
1-2.対数増殖期にある毛乳頭細胞を、専用の毛乳頭細胞増殖培地（PCGM、東洋紡績（株）より購入）で3×10４cells／mlに調製し、1mlを24-well plate（collagen-coated）に植え継いで、37℃の条件で一晩培養した。顕微鏡観察によって細胞の生育状況を確認した後、培養液全量を交換した。 1-2. Prepare the dermal papilla cells in the logarithmic growth phase to 3 × 10 4 cells / ml using a dedicated dermal papilla cell growth medium (PCGM, purchased from Toyobo Co., Ltd.). (Collagen-coated), and cultured overnight at 37 ° C. After confirming the growth state of the cells by microscopic observation, the whole culture solution was exchanged.
1-3.培養液中に表１の被検サンプル又は表２の参考及び比較サンプルを添加してインキュベートを開始した。 1-3. The test sample in Table 1 or the reference and comparison samples in Table 2 were added to the culture medium, and incubation was started.
この際、VEGFを産生促進するモデル薬剤として、ミノキシジルを30μM（最終濃度）で使用した。ミノキシジルは不安定で分解されやすいため、１日毎に培養液中に添加した。 At this time, minoxidil was used at 30 μM (final concentration) as a model drug for promoting VEGF production. Since minoxidil is unstable and easily decomposed, it was added to the culture every day.
1-4.1日毎に250μlの培養液をサンプリングし、4℃で保存した。 1-4. Every day, 250 μl of the culture solution was sampled and stored at 4 ° C.
1-5.2日目のサンプリングを行った後、Human VEGF ELISAキット（R&D SYSTEMS:DY293B）を用いて各サンプル中のVEGF濃度を測定した。 After sampling on day 1-5.2, the VEGF concentration in each sample was measured using a Human VEGF ELISA kit (R & D SYSTEMS: DY293B).
陰性対照試験は、被検サンプルを添加せずに、抽出溶媒のみを添加した反応液とした。 The negative control test was a reaction solution to which only the extraction solvent was added without adding the test sample.
2.毛乳頭細胞でのFGF-7の遺伝子発現の解析
以下の手順で、毛乳頭細胞からtotal RNAを抽出し、FGF-7の遺伝子発現解析を行った。
2. Analysis of gene expression of FGF-7 in dermal papilla cells Total RNA was extracted from dermal papilla cells and analyzed for gene expression of FGF-7 by the following procedure.
2-1.毛乳頭細胞（3×10４cells／ml）を24-well plate（collagen-coated）に植え継ぎ、37℃の条件で一晩培養した。 2-1. Papilla cells (3 × 10 4 cells / ml) were transplanted to a 24-well plate (collagen-coated) and cultured overnight at 37 ° C.
2-2.培養液全量を交換した後、表１の被検サンプル又は表２の参考及び比較サンプルを培養液中に添加し、37℃で1〜2時間インキュベートした。この際、FGF-7の発現誘導剤としてアデノシンを100μM（最終濃度）で使用した。これまで、FGF-7は、毛乳頭細胞から産生され、毛母細胞に作用し、毛母細胞の増殖、分裂を促すことで毛髪を成長させること、そして、アデノシンが毛乳頭細胞表面の受容体に直接作用し、FGF-7（fibroblast growth factor 7、発毛因子）の産生を高めることが、報告されている。 2-2. After exchanging the total amount of the culture solution, the test sample in Table 1 or the reference and comparison samples in Table 2 were added to the culture solution and incubated at 37 ° C. for 1-2 hours. At this time, adenosine was used at 100 μM (final concentration) as an expression inducer of FGF-7. Until now, FGF-7 has been produced from dermal papilla cells and acts on hair matrix cells to promote hair matrix cell proliferation and division to grow hair, and adenosine is a receptor on the surface of dermal papilla cells It has been reported that it acts directly on FGF-7 and increases the production of FGF-7 (fibroblast growth factor 7, hair growth factor).
2-3.培養液を除き、細胞を1mlのISOGEN（株式会社ニッポンジーン製）に溶解し、5分間静置した。細胞溶解液を1.5mlチューブに採取し、0.2mlのクロロホルムを加えて激しく転倒混和した。遠心分離（12,000rpm、4℃、10分）し、水層を新しい1.5mlチューブに採取し、等量の70重量%エタノールを加えた。この溶液全量をRNeasy Mini Kit（株式会社キアゲン製）に付属するスピンカラムにアプライし、製造会社が推奨するプロトコルに従ってtotal RNAを精製した。100ngのtotal RNAを鋳型とし、SuperScript III Reverse Transcriptase （Invitrogen社製）を用いてcDNAを合成した。 2-3. The culture solution was removed, and the cells were dissolved in 1 ml of ISOGEN (manufactured by Nippon Gene Co., Ltd.) and allowed to stand for 5 minutes. The cell lysate was collected in a 1.5 ml tube, 0.2 ml of chloroform was added, and the mixture was vigorously inverted. Centrifugation (12,000 rpm, 4 ° C., 10 minutes), the aqueous layer was collected in a new 1.5 ml tube, and an equal amount of 70 wt% ethanol was added. The total amount of this solution was applied to a spin column attached to RNeasy Mini Kit (manufactured by Qiagen), and total RNA was purified according to a protocol recommended by the manufacturer. Using 100 ng of total RNA as a template, cDNA was synthesized using SuperScript III Reverse Transcriptase (Invitrogen).
2-4.この反応液２μl（合成したcDNA）を鋳型とし、SYBR Premix EX Taq II（タカラバイオ株式会社製）及びLightCycler 480（ロシュ・ダイアグノスティックス株式会社製）を用いてreal-time PCRを行った。 2-4. Real-time PCR using SYBR Premix EX Taq II (manufactured by Takara Bio Inc.) and LightCycler 480 (manufactured by Roche Diagnostics) using 2 μl of this reaction solution (synthesized cDNA) as a template. Went.
対照試験は、被検サンプルを添加せずに、抽出溶媒のみを添加した反応液とした。 In the control test, a reaction solution in which only the extraction solvent was added without adding the test sample was used.
3.5-α-リダクターゼ活性測定
更に、以下の手順で、5-α-リダクターゼの活性測定を行った。
3.5-α-Reductase Activity Measurement Furthermore, the activity of 5-α-reductase was measured according to the following procedure.
5-α-リダクターゼは、NADPHの存在下で、テストステロンをジヒドロテストステロン（DHT）に変換する働きを持つ酵素である。DHTは、その後3α-HSD(3α-hydroxysteroid dehydrogenase)により、A-diol（3α-Androstanediol）に変換される。これまで、変換されたDHTは脱毛を引き起こす直接的な原因物質であり、5-α-リダクターゼ活性を抑制することで、脱毛抑制に繋がることが、報告されている。そして、DHT及びA-diolの合計量を定量することで、5-α-リダクターゼの活性を評価することができる。5-α-リダクターゼとして、ラット肝臓ホモジネートS-9（オリエンタル酵母：636-00221）を使用した。 5-α-reductase is an enzyme that functions to convert testosterone to dihydrotestosterone (DHT) in the presence of NADPH. DHT is then converted to A-diol (3α-Androstanediol) by 3α-HSD (3α-hydroxysteroid dehydrogenase). So far, it has been reported that the converted DHT is a direct causative substance that causes hair loss, and that it suppresses hair loss by suppressing 5-α-reductase activity. Then, by quantifying the total amount of DHT and A-diol, the activity of 5-α-reductase can be evaluated. Rat liver homogenate S-9 (Oriental yeast: 636-00221) was used as 5-α-reductase.
3-1.2ml チューブ内に、下記表３に従って被検サンプルを含む反応液を調製した。ネガティブコントロールは、DHTの合成に必須であるNADPHを含まない反応液とした。ポジティブコントロールは、既存の5-α-リダクターゼ阻害剤であるフィナステリド（Finasteride）を最終濃度0.5μMで使用し、抽出溶媒（エタノール、1,3-ブチレングリコール又は水）を含む反応液とした。 A reaction solution containing a test sample was prepared in a 3-1.2 ml tube according to Table 3 below. The negative control was a reaction solution that did not contain NADPH, which is essential for DHT synthesis. As a positive control, finasteride, an existing 5-α-reductase inhibitor, was used at a final concentration of 0.5 μM, and a reaction solution containing an extraction solvent (ethanol, 1,3-butylene glycol or water) was used.
3-2.調製した反応液を37℃で１時間インキュベートした。 3-2. The prepared reaction solution was incubated at 37 ° C. for 1 hour.
3-3.500μlのジクロロメタン（塩化メチレン）を加え、ボルテックスミキサーで激しく混合した。遠心分離（9,000 rpm、10分）を行い、ジクロロメタン層をガラス瓶に回収した。窒素ガスを吹き付け、溶媒を揮発させた。 3-3.500 μl of dichloromethane (methylene chloride) was added and mixed vigorously with a vortex mixer. Centrifugation (9,000 rpm, 10 minutes) was performed, and the dichloromethane layer was collected in a glass bottle. Nitrogen gas was blown to volatilize the solvent.
3-4.試料を40μlのメタノールに溶解し、10μlをガスクロマトグラフィ（GC）で分析した。GC分析条件は、使用装置：GC-2014（株式会社島津製作所製）、カラム：TC-1（ジーエルサイエンス株式会社製）、カラム温度：240℃、気化室温度：300℃、検出器（温度）：FID（300℃）、入口圧：100kPa、スプリット比：50、キャリアガス：ヘリウム、注入量：10μl、RUN time：25分である。 3-4. A sample was dissolved in 40 μl of methanol, and 10 μl was analyzed by gas chromatography (GC). GC analysis conditions are as follows: Equipment used: GC-2014 (manufactured by Shimadzu Corporation), column: TC-1 (manufactured by GL Sciences Inc.), column temperature: 240 ° C, vaporization chamber temperature: 300 ° C, detector (temperature) : FID (300 ° C.), inlet pressure: 100 kPa, split ratio: 50, carrier gas: helium, injection amount: 10 μl, RUN time: 25 minutes.
3-5.GC分析によって得られたDHTとA-diolの物質量を合計し、テストステロンから生成されたDHTの総量を算出した。算出したDHTの総量から、5-α-リダクターゼ活性の程度を評価した。つまり、反応液にフィナステリドを添加した場合の5-α-リダクターゼに対する阻害率を100%とし（ポジティブコントロール）、各被検サンプルの相対的な阻害率をそれぞれ算出した。 3-5. The amounts of DHT and A-diol obtained by GC analysis were added together to calculate the total amount of DHT produced from testosterone. From the calculated total amount of DHT, the degree of 5-α-reductase activity was evaluated. That is, the inhibition rate with respect to 5-α-reductase when finasteride was added to the reaction solution was defined as 100% (positive control), and the relative inhibition rate of each test sample was calculated.
(3)試験結果
毛乳頭細胞が産生したVEGF量及びFGF-7の遺伝子発現量について、下記の基準に従って評価した。
(3) Test Results The amount of VEGF produced by hair papilla cells and the gene expression level of FGF-7 were evaluated according to the following criteria.
◎：陰性対照に対して50%以上向上
○：陰性対照に対して20%以上向上
△：陰性対照に対して10%以上向上
×：陰性対照に対して数値の向上が10%未満
また、5-α-リダクターゼ活性阻害効果について、下記の基準に従って評価した。
◎: More than 50% improvement over negative control ○: More than 20% improvement over negative control △: More than 10% improvement over negative control ×: Less than 10% improvement over negative control The -α-reductase activity inhibitory effect was evaluated according to the following criteria.
◎：50%以上阻害
○：20%以上阻害
△：10%以上阻害
×：阻害効果が10%未満
被検サンプルの試験結果を下記表４に示した。
◎: 50% or more inhibition ○: 20% or more inhibition Δ: 10% or more inhibition ×: Inhibitory effect is less than 10% Table 4 below shows the test results of the test samples.
参考及び比較サンプルの試験結果は下記表５に示した。 The test results of the reference and comparative samples are shown in Table 5 below.
更に前記アロエ（アロエ・エルー、アロエ・カメロニー、アロエ・ケドンゲンシス、アロエ・フェロックス、アロエ・アフリカーナ、アロエ・アンドンゲンシス及びアロエ・トーメントーサ、並びにキダチアロエとアロエベラとの交配種）に換えて、アロエ・フェロックスとアロエ・アフリカーナとの交配種、アロエ・スピカータ（学名：Aloe spicata）、アロエ・ノビリス（学名：Aloe nobilis）、アロエ・コンパクタ（学名：Aloe compacta）、アロエ・サポナリア（学名：Aloe saponaria）、アロエ・マルロシー／アロエ・マーロシー（学名：Aloe marlothii）、アロエ・ベラ・バリエイタス・キネンシス（学名：Aloe vera var. chinensis）、アロエ・マウイー（学名：Aloe mawii）、アロエ・ルーペストリス（学名：Aloe rupestris）、アロエ・マイクロスティグマ（学名：Aloe microstigma）、アロエ・バイネシー（学名：Aloe bainesii）、アロエ・ボルケンシー（学名：Aloe volkensii）、アロエ・アローイデス（学名：Aloe alooides）、アロエ・アキュレアータ／アロエ・アクレアータ（学名：Aloe aculeata）、アロエ・トラスキー（学名：Aloe thraskii）、アロエ・デラエティ（学名：Aloe delaetii）、アロエ・エスクレンタ（学名：Aloe esculenta）、アロエ・フォルケンジー（学名：Aloe volkensii）及びアロエ・ドロセア（学名：Aloe dorotheae）を用いて、前記アロエと同様にアロエエキスを調製した。そして、これらアロエエキスについても、前記アロエと同様にVEGF産生量を測定した。 In addition, the aloe (aloe vera, aloe camerony, aloe kedongensis, aloe ferrox, aloe africana, aloe andongensis and aloe tormentosa, and a hybrid of alga vera and aloe vera) -Hybrids between Ferrox and Aloe Africana, Aloe spicata (scientific name: Aloe spicata), Aloe nobilis (scientific name: Aloe nobilis), Aloe compacta (scientific name: Aloe compacta), Aloe saponaria (scientific name: Aloe saponaria) ), Aloe Marrothy / Aloe Marlothii (scientific name: Aloe marlothii), Aloe vera var. Chinensis (scientific name: Aloe vera var. Chinensis), Aloe mawii (scientific name: Aloe mawii), Aloe Lupestris (scientific name: Aloe) rupestris), aloe microstigma (scientific name) Aloe microstigma), Aloe banesii (scientific name: Aloe bainesii), Aloe volkensii (scientific name: Aloe alooides), Aloe aculeata / Aloe aculeata (scientific name: Aloe aculeata), Aloe Using Truskey (scientific name: Aloe thraskii), Aloe de laeti (scientific name: Aloe delaetii), Aloe Escrenta (scientific name: Aloe esculenta), Aloe Falkens (scientific name: Aloe volkensii) and Aloe dorothea (scientific name: Aloe dorotheae) Then, an aloe extract was prepared in the same manner as the aloe. And also about these aloe extracts, the amount of VEGF production was measured similarly to the said aloe.
その結果、アロエ・フェロックスとアロエ・アフリカーナとの交配種、アロエ・スピカータ、アロエ・ノビリス、アロエ・コンパクタ、アロエ・サポナリア、アロエ・マルロシー／アロエ・マーロシー、アロエ・ベラ・バリエイタス・キネンシス、アロエ・マウイー、アロエ・ルーペストリス、アロエ・マイクロスティグマ、アロエ・バイネシー、アロエ・ボルケンシー、アロエ・アローイデス、アロエ・アキュレアータ／アロエ・アクレアータ、アロエ・トラスキー、アロエ・デラエティ及びアロエ・エスクレンタ、アロエ・フォルケンジー、アロエ・ドロセアから抽出されたアロエエキスについても、VEGF産生促進効果が確認された。 As a result, crosses between Aloe Ferrox and Aloe Africana, Aloe Spicata, Aloe Nobilis, Aloe Compactor, Aloe Saponaria, Aloe Marlosi / Aloe Marrosy, Aloe Bella Varietas Kinensis, Aloe Maui, Aloe Lupestris, Aloe Microstigma, Aloe Vinecy, Aloe Volkensee, Aloe Arroides, Aloe Acureata / Aloe Acreata, Aloe Trusky, Aloe Delaetti and Aloe Escrenta, Aloe Falkens, Aloe Aloe extract extracted from Dorothea was also confirmed to promote VEGF production.
これらのことから、上記種のアロエ植物体も、本発明と同様に、VEGF産生促進剤、育毛及び／又は発毛促進剤の有効成分となるアロエエキスの原料として用いることができると考えられる。 From these facts, it is considered that the aloe plant of the above kind can also be used as a raw material for an aloe extract that is an active ingredient of a VEGF production promoter, hair growth and / or hair growth promoter, as in the present invention.
試験結果から、表４に記載のアロエエキスにおいて、VEGF産生促進の効果が確認された。 From the test results, in the aloe extract shown in Table 4, the effect of promoting VEGF production was confirmed.
また、表５より、FGF-7遺伝子の発現量を増加させる成分及び5-α-リダクターゼ活性を阻害させる成分が、必ずしもVEGF産生を促進するものではないことが明らかとなった。例えば、アセンヤクエキス及びカワラヨモギエキスは、5-α-リダクターゼ活性を阻害させるが、VEGF産生促進効果は見られなかった。また、ローヤルゼリー酸は、FGF-7遺伝子発現量を増加させるが、VEGF産生促進効果は見られなかった。 Table 5 also revealed that components that increase the expression level of the FGF-7 gene and components that inhibit 5-α-reductase activity do not necessarily promote VEGF production. For example, Acacia yak extract and Kawara mugwort extract inhibit 5-α-reductase activity, but no VEGF production promoting effect was observed. Furthermore, royal jelly acid increased the expression level of FGF-7 gene, but did not show an effect of promoting VEGF production.
つまり、使用するアロエエキスによっては、これまで育毛促進及び脱毛抑制に関与すると報告されていたFGF-7遺伝子発現量及び5-α-リダクターゼ活性阻害と、VEGF産生促進効果との間には、必ずしも相関関係があるわけではないことが明らかになった。 In other words, depending on the aloe extract used, the FGF-7 gene expression level and 5-α-reductase activity inhibition, which have been reported to be involved in hair growth promotion and hair loss suppression, and the VEGF production promotion effect are not necessarily It became clear that there was no correlation.
そして、本発明によって、初めて、特定の種のアロエ（アロエ・エルー、アロエ・カメロニー、アロエ・ケドンゲンシス、アロエ・フェロックス、アロエ・アフリカーナ、アロエ・アンドンゲンシス及びアロエ・トーメントーサ、並びにキダチアロエとアロエベラとの交配種）から抽出されたアロエエキスには、育毛促進及び脱毛抑制の中でも、VEGF産生を促進する効果に優れることが確認された。 And for the first time, according to the present invention, certain species of aloe (Aloe Elue, Aloe Camellony, Aloe Kedongensis, Aloe Ferrox, Aloe Africana, Aloe Andogensis and Aloe Tormentosa, as well as Kidachi Aloe and Aloe Vera It has been confirmed that the aloe extract extracted from the hybrid species) is excellent in the effect of promoting VEGF production among hair growth promotion and hair loss inhibition.
また、特定の種のアロエエキスにより、VEGFの産生量が高められる結果、血管新生が促され、毛細血管の生成も高められ、また、特定の種のアロエエキスを用いることにより、優れた育毛効果及び発毛効果が期待できる。 In addition, as a result of increasing the amount of VEGF produced by a specific species of aloe extract, angiogenesis is promoted, and the generation of capillaries is also enhanced. Moreover, the hair growth effect can be expected.
そこで、更に、特定の種のアロエエキスを用いて、発毛促進作用及び育毛促進作用の効果を確認した。 Then, the effect of hair growth promoting action and hair growth promoting action was further confirmed using a specific species of aloe extract.
実験例２ アロエエキスによる育毛及び発毛促進作用
(1)アロエエキスの調製
アロエ植物体として、アロエ・エルー、アロエ・ケドンゲンシス、アロエ・トーメントーサ、及びキダチアロエとアロエベラとの交配種を用いて、上記実験例１と同様にして、アロエエキス（抽出溶媒：90重量%エタノール水溶液）を調製した。
Experimental Example 2 Hair growth and hair growth promoting action by aloe extract
(1) Preparation of Aloe Extract Aloe extract (extraction) was carried out in the same manner as in Experimental Example 1 above, using aloe vera, aloe kedongensis, aloe tomentosa, and a hybrid of alba vera and aloe vera. Solvent: 90 wt% aqueous ethanol solution) was prepared.
得られた各アロエエキスの詳細を表６に示した。表中、EtOHはエタノールを示す。 The details of each obtained aloe extract are shown in Table 6. In the table, EtOH represents ethanol.
(2)マウスの育毛及び発毛促進作用の評価
以下の手順で、マウスの皮膚に対する育毛及び発毛促進効果を評価した。
(2) Evaluation of mouse hair growth and hair growth promoting action The following procedures evaluated hair growth and hair growth promoting effects on mouse skin.
1.アロエエキスを固形分3重量%となるように50重量%エタノール水溶液に溶解し、試験サンプルとした。陰性対照として、50重量%エタノール水溶液（50%EtOH）を用いた。 1. Aloe extract was dissolved in a 50 wt% aqueous ethanol solution to a solid content of 3 wt% to prepare a test sample. As a negative control, a 50 wt% aqueous ethanol solution (50% EtOH) was used.
2.バリカン及びカミソリで除毛したマウスの背部皮膚に、1日1回、18日間の連日で、試験サンプルを塗布投与した。マウスはC3H/HeNCrlCrlj（SPF）を用いて、各群10匹とした。 2. The test sample was applied and administered once a day for 18 days on the back skin of mice that had been depilated with hair clippers and razors. There were 10 mice in each group using C 3 H / HeNCrlCrlj (SPF).
3.投与開始日を投与1日目とし、最終投与翌日までの除毛部位内（約3×5cm）の様子を観察した。 3. The first day of administration was taken as the first day of administration, and the appearance within the hair removal site (about 3 × 5 cm) until the day after the last administration was observed.
4.育毛及び発毛促進の程度を、表７の毛再生スコアで判定し、各スコアの平均値を求めた（「皮膚と美容」,Vol31 No.4,5512-5518,1999参照）。更に毛の状態を示す写真を一定条件下にて撮影した。 4. The degree of hair growth and hair growth promotion was determined by the hair regeneration score in Table 7, and the average value of each score was obtained (see “Skin and Beauty”, Vol 31 No. 4, 5512-5518, 1999). Furthermore, photographs showing the state of hair were taken under certain conditions.
(3)試験結果
陰性対照、アロエ・エルー、アロエ・ケドンゲンシス及びアロエ・トーメントーサ、並びにキダチアロエとアロエベラとの交配種の11日目の毛再生スコアの平均値に基づき、各アロエエキスの育毛及び発毛促進効果を、陰性対照を100%とした育毛・発毛率で表８に示した。
(3) Hair growth and development of each aloe extract based on the average value of the hair regeneration score on the 11th day of the negative control, aloe eru, aloe kedongensis and aloe tormentosa, and the hybrid of Kidachi aloe and aloe vera The hair promoting effect is shown in Table 8 in terms of hair growth / growth rate with the negative control as 100%.
試験結果から、陰性対照（50%EtOH）と比較して、アロエ・エルー、アロエ・ケドンゲンシス及びアロエ・トーメントーサ、並びにキダチアロエとアロエベラとの交配種は、優れた育毛及び発毛促進効果を示した。また、上記実験例１と同様にしてキダチアロエのエキス（抽出溶媒：90重量%エタノール水溶液）を調製し、実験例２と同様に育毛及び発毛促進効果を評価したところ、アロエ・エルー、アロエ・ケドンゲンシス及びアロエ・トーメントーサ、並びにキダチアロエとアロエベラとの交配種のいずれも、キダチアロエに比べて優れた効果を示した。 From the test results, compared with the negative control (50% EtOH), the hybrids of Aloe Elue, Aloe Kedon Gensis and Aloe Tormentosa, and Kidachi Aloe and Aloe Vera showed excellent hair growth and hair growth promoting effects. . In addition, a Kidachi aloe extract (extraction solvent: 90 wt% ethanol aqueous solution) was prepared in the same manner as in Experimental Example 1 and evaluated for hair growth and hair growth promoting effects in the same manner as in Experimental Example 2. Kedon Gensis and Aloe Tormentosa, as well as hybrids of Kidachi Aloe and Aloe Vera all showed superior effects compared to Kidachi Aloe.
特にアロエ・ケドンゲンシス及びアロエ・トーメントーサ、並びにキダチアロエとアロエベラとの交配種では、その効果が顕著であった。
また、アロエ・トーメントーサは、試験期間中のいずれにおいても、キダチアロエを上回る良好な育毛・発毛率を示した。更に、陰性対照、キダチアロエ及びアロエ・トーメントーサの１９日目における育毛及び発毛促進効果を図１に示す。図１からも分かるように、アロエ・トーメントーサは、キダチアロエに比べて非常に優れた育毛及び発毛促進効果を示した。
In particular, the effects were remarkable in aloe kedon gensis and aloe tomentosa, as well as in hybrids of Kidachi aloe and aloe vera.
In addition, aloe tomentosa showed good hair growth / growth rate higher than that of Kidachi aloe in any of the test periods. Further, FIG. 1 shows the effects of hair growth and hair growth on the 19th day of the negative control, Kidachi aloe and Aloe tomentosa. As can be seen from FIG. 1, aloe tomentosa showed excellent hair growth and hair growth promoting effects as compared with Kidachi aloe.
また、キダチアロエ（従来種、比較例）と比較して、アロエ・エルーは、試験期間11日目、13日目、19日目において、優れた育毛及び発毛促進効果を示した。キダチアロエとアロエベラとの交配種は、試験期間11日目、17日目において、優れた育毛及び発毛促進効果を示した。 In addition, compared with Kidachi aloe (conventional species, comparative example), Aloe EL showed excellent hair growth and hair growth promoting effects on the 11th, 13th, and 19th days of the test period. The hybrid of Kidachi aloe and aloe vera showed excellent hair growth and hair growth promoting effects on the 11th and 17th days of the test period.
参考として、表９にキダチアロエ、アロエ・エルー及びアロエ・トーメントーサにおけるアロエニン含有量を示す。アロエニンは、キダチアロエ等に含まれ、発毛及び育毛を促進する効果が有ると言われている有効成分である。なお、各種アロエに含まれるアロエニンの含有量については、高速液体クロマトグラフィー法にて定量した。 For reference, Table 9 shows the content of aloenin in Kidachi aloe, Aloe leu and Aloe tomentosa. Aloenin is an active ingredient which is contained in Kidachi aloe and is said to have an effect of promoting hair growth and hair growth. In addition, about the content of aloenin contained in various aloe, it quantified by the high performance liquid chromatography method.
一方、アロエ・エルー及びアロエ・トーメントーサには、アロエニンが検出されず、アロエニンが含有されていないことがわかった。しかしながら、試験結果から、アロエ・エルー及びアロエ・トーメントーサにおいて、発毛促進の効果が確認された。このことは、特定の種から抽出されたアロエエキスでは、アロエニンが含まれていなくても、発毛促進の効果を奏することが明らかとなった。つまり、使用するアロエエキスによっては、アロエニンと発毛促進及び育毛促進の効果との間には、必ずしも相関関係があるわけではないことが明らかになった。 On the other hand, it was found that no aloenin was detected in aloe elu and aloe tomentosa, and no aloenin was contained. However, the test results confirmed the effect of promoting hair growth in Aloe Elue and Aloe Tormentosa. This indicates that the aloe extract extracted from a specific species has an effect of promoting hair growth even if it does not contain aloenin. That is, depending on the aloe extract used, it has been clarified that there is not necessarily a correlation between aloenin and the effects of promoting hair growth and promoting hair growth.
この様に、本発明によって、初めて、特定の種のアロエエキスには、アロエニンが含まれていなくとも、発毛促進及び育毛促進の効果を奏することが確認された。更に、特定の種のアロエエキスは、従来のキダチアロエ（従来種、比較例）と比較して、優れた育毛促進及び発毛促進の効果を奏することも確認された。 Thus, according to the present invention, for the first time, it has been confirmed that a specific type of aloe extract has an effect of promoting hair growth and promoting hair growth even if it does not contain aloenin. Furthermore, it was also confirmed that the aloe extract of a specific species has an excellent effect of promoting hair growth and promoting hair growth as compared with the conventional Kidachi aloe (conventional species, comparative example).
実験例３ アロエエキスによる線虫寿命延長作用
線虫寿命延長試験は、細胞の寿命に対する延長作用を評価するために利用されている。ここでは、線虫寿命延長試験を用いて、アロエエキスの細胞（毛乳頭細胞）の寿命に対する延長作用を評価した。
Experimental Example 3 Nematode Life Extension Action by Aloe Extract The nematode life extension test is used to evaluate the extension action on cell life. Here, the extension effect | action with respect to the lifetime of the cell (hair papilla cell) of an aloe extract was evaluated using the nematode lifetime extension test.
(1)線虫寿命延長の試験
以下の手順で、線虫（Caenorhabditis elegans）を用いて、毛乳頭細胞の寿命の延長効果を評価した。
1.同一生育ステージの線虫を得るため、産卵期にある成虫から卵を回収した。具体的には、卵を抱えた線虫をS-bufferで回収し、漂白剤及びNaOH溶液を用いて成虫を溶解することにより卵のみを得た。
2.卵はS-bufferに入れ、20℃で一晩かけて孵化させた。
3.生育ステージを合わせたL1期幼虫を、大腸菌を加えたS-mediumに移した。線虫2,000匹を液体培地10mLに加え、50mLの三角フラスコで3日間培養し、成虫とした。
4. アンピシリン20μl（Final 200μg/ml）と陰性対照（0.25%重量エタノール,被験物質の溶媒）若しくは被験物質（アロエエキス）を入れ培養した。
5.線虫寿命の測定は2〜3日に一度、一定量をサンプリングしてその中の線虫の生死数をカウントした。線虫の生死数カウントは4回行い、統計処理に用いた。線虫の生存率については、以下の式(1）にしたがって算出した。
(1) Test of extension of nematode life The effect of extending the life of hair papilla cells was evaluated using nematodes (Caenorhabditis elegans) by the following procedure.
1. In order to obtain nematodes of the same growth stage, eggs were collected from adults in the spawning season. Specifically, nematodes carrying eggs were collected with S-buffer, and only eggs were obtained by dissolving adults using bleach and NaOH solution.
2. Eggs were placed in S-buffer and allowed to hatch overnight at 20 ° C.
3. The L1 stage larvae combined with the growth stage were transferred to S-medium supplemented with E. coli. 2,000 nematodes were added to 10 mL of liquid medium and cultured in a 50 mL Erlenmeyer flask for 3 days to form adults.
4. 20 μl of ampicillin (Final 200 μg / ml) and negative control (0.25% by weight ethanol, test substance solvent) or test substance (aloe extract) were added and cultured.
5. The nematode lifespan was measured once every 2-3 days, and a certain amount was sampled to count the number of live nematodes. The nematode viability count was performed 4 times and used for statistical processing. The nematode survival rate was calculated according to the following equation (1).
式(1）：線虫の生存率(%)＝100×生存している線虫／(生存している線虫+死んだ線虫) Formula (1): Survival rate of nematode (%) = 100 × surviving nematode / (surviving nematode + dead nematode)
(2)線虫寿命延長の試験の評価結果
キダチアロエ（従来種、比較例）及びアロエ・トーメントーサの線虫寿命延長試験を実施した。
(2) Evaluation results of the nematode life extension test A nematode life extension test was carried out for Kidachi aloe (conventional species, comparative example) and aloe tomentosa.
寿命延長効果を示したアロエ・トーメントーサの結果を表１０に示した。 Table 10 shows the results of Aloe tomentosa showing the effect of extending the life.
＊p＜0.05 (vs. Ethanol)、＊＊p＜0.01 (vs. Ethanol) * P <0.05 (vs. Ethanol), ** p <0.01 (vs. Ethanol)
試験結果から、アロエ・トーメントーサは、陰性対照（0.25%重量エタノール）と比べて、有意に寿命を延長させることが示された。つまり、本発明によって、初めて、特定の種のアロエエキスには、線虫の寿命を延長させる効果を奏することが確認され、細胞の寿命を延長させる可能性があることが示された。 The test results showed that aloe tomentosa significantly extended life compared to the negative control (0.25% ethanol by weight). That is, for the first time according to the present invention, it has been confirmed that a specific species of aloe extract has an effect of extending the life of nematodes, and has the possibility of extending the life of cells.
この試験結果から、特定の種のアロエから抽出したアロエエキスは、毛乳頭細胞の寿命を延長させる効果があることが示唆された。 From this test result, it was suggested that an aloe extract extracted from a specific species of aloe has an effect of extending the life of hair papilla cells.
実験例４ アロエエキス安定性の試験
以下の手順で、アロエエキスの安定性を評価した。
Experimental Example 4 Aloe extract stability test The stability of the aloe extract was evaluated by the following procedure.
1.被験物質（アロエエキス）が固形分濃度0.75重量%となるよう、90重量%エタノール水溶液（90%EtOH水溶液）に溶解し、試験サンプルとした。 1. The test substance (aloe extract) was dissolved in a 90 wt% aqueous ethanol solution (90% EtOH aqueous solution) so that the solid content concentration was 0.75 wt%, and used as a test sample.
2.試験サンプルを、5℃、1週間程度静置し、外観を観察した。 2. The test sample was allowed to stand at 5 ° C for about 1 week, and the appearance was observed.
アロエエキス安定性の試験及び評価結果
キダチアロエ（従来種、比較例）及びアロエ・ケドンゲンシスの90%EtOH水溶液中の安定性の試験の結果を示した。
Aloe extract stability test and evaluation results The results of stability test in 90% EtOH aqueous solution of Kidachi aloe (conventional species, comparative example) and aloe kedongensis were shown.
各試験サンプルの90%EtOH水溶液中での透明度を観察した（表１１）。 The transparency of each test sample in 90% EtOH aqueous solution was observed (Table 11).
表中「○」評価は外観性状が均一で透明であることを示し、「×」評価は外観性状に濁りがあり不均一であることを示す。 In the table, “◯” indicates that the appearance is uniform and transparent, and “x” indicates that the appearance is turbid and non-uniform.
キダチアロエ（従来種）は、90%EtOH水溶液中において濁りが生じた。 Kidachi aloe (conventional species) was turbid in 90% EtOH aqueous solution.
一方、アロエ・ケドンゲンシスは、90%EtOH水溶液中において濁りが生じず、透明であった。つまり、キダチアロエ（従来種）と比較して、アロエ・ケドンゲンシスは、エタノール水溶液中での安定性が優れていることが確認できた。 On the other hand, Aloe Kedongensis was transparent with no turbidity in 90% EtOH aqueous solution. In other words, it was confirmed that aloe ketogensis is superior in stability in an aqueous ethanol solution as compared to Kidachi aloe (conventional species).
育毛剤及び発毛剤は、通常多量のエタノールを含む。そのため、特定の種のアロエエキスが、エタノール水溶液中で安定に存在することは、育毛剤及び発毛剤へ配合することに適していることが示唆された。 Hair growth agents and hair growth agents usually contain large amounts of ethanol. Therefore, it was suggested that the presence of a specific species of aloe extract stably in an aqueous ethanol solution is suitable for blending into a hair restorer and a hair growth agent.
上記試験結果より、種々のアロエエキスの中でも、アロエ・エルー、アロエ・ケドンゲンシス及びアロエ・トーメントーサ、並びにキダチアロエとアロエベラとの交配種からなる群より選択される少なくとも１種から抽出されたアロエエキスが、優れた育毛効果及び発毛効果を奏することが立証された。 From the above test results, among the various aloe extracts, aloe extract extracted from at least one selected from the group consisting of aloe eru, aloe kedongensis and aloe tomentosa, and a hybrid of kidachi aloe and aloe vera It was proved that the hair growth effect and the hair growth effect were excellent.
更に、本発明の育毛及び／又は発毛促進剤は、特定の種のアロエエキスを有効成分とすることにより、育毛剤及び発毛剤に適用しても、製品としての優れた安定性を奏することが期待できる。 Furthermore, the hair growth and / or hair growth promoter of the present invention exhibits excellent stability as a product even when applied to a hair growth agent and a hair growth agent by using a specific species of aloe extract as an active ingredient. I can expect that.
処方例
以下、本発明に係る育毛及び／又は発毛剤原料を配合した、育毛及び／又は発毛剤組成物の処方例を表１２〜１６に示す。いずれの組成物においても、優れた育毛及び発毛促進効果が示された。
Formulation Examples Hereinafter, Tables 12 to 16 show formulation examples of the hair growth and / or hair growth composition containing the hair growth and / or hair growth material according to the present invention. In any composition, excellent hair growth and hair growth promoting effects were shown.
育毛及び発毛用ローション（表１２）Hair growth and hair growth lotion (Table 12)
育毛シャンプー（表１３）Hair growth shampoo (Table 13)
育毛クリーム（表１４）Hair growth cream (Table 14)
頭皮用美容液（表１５）Scalp serum (Table 15)
錠剤（表１６）Tablet (Table 16)
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| JP7064820B2 (en) * | 2016-03-31 | 2022-05-11 | ピアス株式会社 | Use of hair restorer, and ε-polylysine and / or peony extract |
| JP6974928B2 (en) | 2017-10-10 | 2021-12-01 | ザ プロクター アンド ギャンブル カンパニーThe Procter & Gamble Company | Compact shampoo composition |
| CA3159404A1 (en) | 2019-12-06 | 2021-06-10 | The Procter & Gamble Company | Sulfate free composition with enhanced deposition of scalp active |
| CN114945410A (en) * | 2020-01-13 | 2022-08-26 | 宝洁公司 | Personal care compositions comprising aloe vera |
| US11986543B2 (en) | 2021-06-01 | 2024-05-21 | The Procter & Gamble Company | Rinse-off compositions with a surfactant system that is substantially free of sulfate-based surfactants |
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