JP5852854B2 - メラノサイト分化誘導抑制剤及びその使用方法 - Google Patents
メラノサイト分化誘導抑制剤及びその使用方法 Download PDFInfo
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- JP5852854B2 JP5852854B2 JP2011250946A JP2011250946A JP5852854B2 JP 5852854 B2 JP5852854 B2 JP 5852854B2 JP 2011250946 A JP2011250946 A JP 2011250946A JP 2011250946 A JP2011250946 A JP 2011250946A JP 5852854 B2 JP5852854 B2 JP 5852854B2
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Description
(1)アイヌワカメの抽出物を有効成分として含有するメラノサイト分化誘導抑制剤。
(2)前記抽出物が水、低級アルコール、液状多価アルコール及び無機酸から成る群より選択される溶媒により抽出された抽出物である、(1)記載のメラノサイト分化誘導抑制剤。
(4)液状多価アルコールが1,3-ブチレングリコールである、(2)記載のメラノサイト分化誘導抑制剤。
(6)(1)〜(5)のいずれか1記載のメラノサイト分化誘導抑制剤を含有する色素異常症改善又は治療用組成物。
(8)幹細胞をメラノサイト分化誘導系において候補物質と接触させる工程と、該候補物質非存在下での該幹細胞と比較して、該候補物質と接触した該幹細胞においてメラニン合成量又はメラノサイトマーカー遺伝子の発現が調節されていることにより、該候補物質がメラノサイト分化誘導調節剤であると判定する工程とを含む、メラノサイト分化誘導調節剤のスクリーニング方法。
上述のように、従来のメラノーマ細胞や最終分化後のメラノサイト及びマッシュルーム由来チロシナーゼ等を用いて行う従来のスクリーニング系ではなく、未分化な幹細胞からメラノサイトへの分化誘導系をスクリーニング系として用いていることにより、メラノサイトの分化自体を抑制する素材の探索を行ったところ、チガイソ科に属するアイヌワカメ(学名:Alaria praelonga Kjellman)の抽出物が、幹細胞からメラノサイトへの分化誘導抑制活性を有することを見出した。
以下に、アイヌワカメを用いた溶媒抽出物の製造例を示す。
1.製造例1 アイヌワカメの熱水抽出物
アイヌワカメの乾燥物20gに精製水800mLを加え、95〜100℃で2時間抽出を行った。抽出後、抽出液を濾過に供し、得られた濾液を濃縮及び凍結乾燥に供することで、アイヌワカメの熱水抽出物を3.4g得た。
アイヌワカメの乾燥物20gに0.1N HCl 800mlを加え、4℃で7日間抽出を行った。抽出後、抽出液を濾過に供し、得られた濾液を濃縮及び凍結乾燥に供することで、アイヌワカメのHCl抽出物を3.1g得た。
アイヌワカメの乾燥物20gに50(v/v)%エタノール400mLを加え、常温で7日間抽出を行った。抽出後、抽出液を濾過に供し、得られた濾液を濃縮乾固に供することで、アイヌワカメの50%エタノール抽出物を3.7g得た。
アイヌワカメの乾燥物100gにエタノール1Lを加え、常温で7日間抽出を行った。抽出後、抽出液を濾過に供し、得られた濾液を濃縮乾固に供することで、アイヌワカメのエタノール抽出物を6.7g得た。
アイヌワカメの乾燥物20gに50%1,3-ブチレングリコール水溶液400mLを加え、常温で7日間抽出を行った。抽出後、抽出液を濾過に供することで、アイヌワカメの50%1,3-ブチレングリコール抽出物を370g得た。
以下に、実施例1において製造した製造例1〜5のアイヌワカメ抽出物を用いて、幹細胞からメラノサイトへの分化誘導抑制効果を評価し、該抽出物のメラノサイトへの分化誘導抑制剤としての効果について確認した。
本実験例では、過去に山根らが開発したマウス胚性幹細胞(ES cell:embryonic stem cell)からのメラノサイト分化誘導系(Yamane T., Hayashi S., Mizoguchi M., Yamazaki H., Kunisada T., Developmental Dynamics, 1999年, Vol. 216, Issue 4-5, pp. 450-458)を用いて、アイヌワカメ抽出物の効果を検討した。本誘導系を用いることで、メラノサイトの発生から成熟までの全ての段階において素材の評価を行うことが可能となる。以下に詳細を説明する。
これらの試験結果を以下の表1に示す。
試験例1と同様に、マウスES細胞からメラノサイトへの分化誘導を実施し、メラノサイトへの分化効率についてメラノサイトの特異的マーカー遺伝子(Mitf-M及びTyrp1)の発現を指標に評価した。
Mitf-M用のプライマーセット:
5'-TGCCTTGTTTATGGTGCCTTCT-3'(配列番号1)、及び
5'-TCCCTCTACTTTCTGTAATTCCAATTC-3'(配列番号2)
Tyrp1用のプライマーセット:
5'-CAACGCTATGCTGAGGACTATGA-3'(配列番号3)、及び
5'-GCGGCTATCAGACCATGGA-3'(配列番号4)
GAPDH用のプライマーセット:
5'-TGCACCACCAACTGCTTAGC-3'(配列番号5)、及び
5'-TCTTCTGGGTGGCAGTGATG-3'(配列番号6)
その結果を下記の表2に示す。
実施例1で製造したアイヌワカメ抽出物について、処方例として下記の製剤化を行った。
成分1〜6及び12と、成分7〜11をそれぞれ均一に溶解した後、双方を混合し、濾過することで製品とした。
処方例1において、アイヌワカメ抽出物を精製水に置き換えたものを従来のローションとした。
成分2〜9を加熱溶解して混合し、70℃に保ち油相とした。また、成分1及び成分11〜14を加熱溶解して混合し、75℃に保ち水相とした。次いで、油相に水相を加えて乳化して、かき混ぜながら冷却し、45℃で成分10を加え、さらに30℃まで冷却することで製品とした。
処方例2において、アイヌワカメ抽出物を精製水に置き換えたものを従来のクリームとした。
成分1〜5を混合し、次いで10%の水を結合剤として加えて、押出し造粒に供した後、乾燥させた。成形した顆粒に成分6を加えて混合し、打錠した。1錠を0.52gとした。
処方例3において、アイヌワカメ抽出物を精製水に置き換えたものを従来の錠剤とした。
成分1〜4を成分5の一部の水に撹拌溶解した。次いで、成分5の残りの水を加えて混合した。
処方例4において、アイヌワカメ抽出物を水に置き換えたものを従来の飲料とした。
実施例3で製造した処方例1のローション及び処方例2のクリーム並びに比較処方例1のローション及び比較処方例2のクリームを用いて、シミ及びくすみに悩む女性30人(18才〜50才)を対象に2ヶ月間の使用試験を行った。
使用後、シミ及びくすみの改善作用をアンケートにより判定した。
結果を表7に示す。
Claims (3)
- アイヌワカメの熱水抽出物又は塩酸抽出物を有効成分として含有する、幹細胞からメラノサイトへの分化誘導抑制剤。
- 請求項1記載の幹細胞からメラノサイトへの分化誘導抑制剤を含有する色素異常症改善又は治療用組成物。
- 請求項1記載の幹細胞からメラノサイトへの分化誘導抑制剤を含有するシミ改善用組成物。
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