JP7277571B2 - イノトジオール化合物を有効成分として含む、アレルギー疾患の予防又は治療用組成物 - Google Patents
イノトジオール化合物を有効成分として含む、アレルギー疾患の予防又は治療用組成物 Download PDFInfo
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- JP7277571B2 JP7277571B2 JP2021516338A JP2021516338A JP7277571B2 JP 7277571 B2 JP7277571 B2 JP 7277571B2 JP 2021516338 A JP2021516338 A JP 2021516338A JP 2021516338 A JP2021516338 A JP 2021516338A JP 7277571 B2 JP7277571 B2 JP 7277571B2
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Description
実施例1-1. カバノアナタケ抽出物の製造及びイノトジオール化合物の含有量の確認
本発明のイノトジオール化合物は、カバノアナタケ(Inonotus obliquus)抽出物から分離した。
前記実施例1-1で得られたカバノアナタケのジクロロメタン画分からイノトジオール化合物を分離した。
Inotodiol;
白色アモルファス粉末;
ESI―MS:[M+ Na]+ 465.37m/z(C30H50O2:442.27);
1H NMR及び13C NMRデータは表1参照;
ESI―MS分析の結果と13C NMRデータによって分子式がC30H50O2であることが確認された。
以上の結果を論文に報告されたデータ(Du.D.,et al.,2011)と比較してイノトジオール化合物の構造を確証することができた。
アレルギーマウスモデルを作製するために、5週齢の雄BALB/Cマウスを用いた。アレルギー誘導物質(アレルゲン、allergen)として鶏の卵白アルブミン(ovalbumin)を用いて食物アレルギーモデルを作製した。
実験例2-1. 直腸(rectal)温度変化の確認
食物アレルギー誘発及び薬物処理による直腸の温度変化を確認するために、各群のマウスを用いて直腸の温度を測定した。直腸の温度は、直腸体温計のセンサーの先端を直腸に挿入して測定し、その結果を図1(A)に示す。
本発明のカバノアナタケから分離したイノトジオール化合物及びこれを含むカバノアナタケのジクロロメタン画分の食物アレルギーによるアナフィラキシー症状の改善又は治療効果を確認するために、各実験群のマウスの反応を観察し、下記表3に基づいてアナフィラキシー症状を点数化し、その結果を図1(B)に示す。
本発明のカバノアナタケから分離したイノトジオール化合物及びこれを含むカバノアナタケのジクロロメタン画分の食物アレルギーによる糞便の形態変化を観察した。各実験群のマウスの大腸内便の形を肉眼で観察し、下記の表4に基づいて下痢症状を点数化し、その結果を図1(C)に示す。
実験例3-1. 小腸の好酸球(eosinophils)の観察
好酸球は、食物アレルギーに重要な役割を果たすと知られている。つまり、好酸球は、小腸でアレルギー性炎症を引き起こす。そこで、小腸における好酸球の変化を観察することによって、本発明のイノトジオール化合物及びこれを含むカバノアナタケのジクロロメタン画分のアレルギー予防及び治療効果を確認した。
アレルギー反応を誘発すると知られている肥満細胞(mast cell)を観察することによって、本発明のイノトジオール化合物及びこれを含むカバノアナタケのジクロロメタン画分のアレルギー予防及び治療効果を確認した。
アレルギー反応は、アレルゲンに反応するIgEの発現に起因してアレルゲンとIgEの結合により、肥満細胞がヒスタミン(histamine)、セリンプロテアーゼ(serine protease)、プロテオグリカン(proteoglycan)などのアレルギー炎症に関連する顆粒物質を分泌するようになる。したがって、本発明のイノトジオール化合物及びこれを含むカバノアナタケのジクロロメタン画分のアレルギー予防及び治療効果を確認するために、マウスの血清中のIgE及び肥満細胞の特異的セリンプロテアーゼであるMCPT-1(mast cell protease- 1)の濃度を測定した。
実験例5-1. CD4+T細胞活性調節効果の確認
Th2(T helper 2)CD4+T細胞によって生成されるサイトカインがIgEの生成を増進し、かつ肥満細胞と好酸球の分化(differentiation)を促進し、アレルギー症状を深めると知られている。また、抗アレルギー効果があると報告されている植物抽出物の場合、CD4+T細胞の活性化とTh2 CD4+T細胞のサイトカイン生成を抑制する効果を同時に持つと多数報告されている。
上記実験例4におけるイノトジオール化合物又はこれを含有するカバノアナタケ抽出物のMCPT-1発現の減少は、イノトジオール化合物による肥満細胞の免疫活性抑制と関連していることが分かった。
製剤例1-1. 錠剤の製造
本発明のカバノアナタケのジクロロメタン画分200gを、ラクトース175.9g、ジャガイモデンプン180g及びコロイド性ケイ酸32gと混合した。この混合物に10%ゼラチン溶液を添加した後、粉砕して14メッシュのふるいに通した。これを乾燥させ、ここにジャガイモデンプン160g、タルク50g及びステアリン酸マグネシウム5gを添加して得られた混合物を錠剤にした。
本発明のイノトジオール化合物1g、塩化ナトリウム0.6g及びアスコルビン酸0.1gを蒸留水に溶解させて100mlを作った。この溶液を瓶に入れて20℃で30分間加熱して滅菌した。
製剤例2-1. 調理用調味料の製造
本発明のイノトジオール化合物を調理用調味料の1重量%で添加して健康増進のための調理用調味料を製造した。
本発明のイノトジオール化合物を小麦粉に0.1重量%で添加し、この混合物を用いてパン、ケーキ、クッキー、クラッカー及び麺類を作ることのよって健康増進用食品を製造した。
本発明のイノトジオール化合物をスープ及び肉汁に0.1重量%で添加して健康増進用スープと肉汁を製造した。
本発明のイノトジオール化合物を牛乳に0.1重量%で添加し、前記牛乳を用いてバター、アイスクリームなどの様々な乳製品を製造した。
本発明のイノトジオール化合物0.5gをトマトジュース又はニンジンジュース1,000mlに加え、健康増進用野菜ジュースを製造した。
本発明のイノトジオール化合物0.1gをリンゴジュース又はグレープジュース1,000mlに加え、健康増進用フルーツジュースを製造した。
Claims (8)
- 前記医薬組成物は、肥満細胞の脱顆粒を抑制することを特徴とする、請求項1に記載のアレルギー疾患の予防又は治療用医薬組成物。
- 前記アレルギーは、花粉、薬物、植物繊維、細菌、食物、染毛剤、化学物質からなる群から選択される1種以上によって誘導されることを特徴とする、請求項1に記載のアレルギー疾患の予防又は治療用医薬組成物。
- 前記アレルギーは、食物によって誘導されるアレルギーであることを特徴とする、請求項3に記載のアレルギー疾患の予防又は治療用医薬組成物。
- 前記健康機能食品組成物は、肥満細胞の脱顆粒を抑制することを特徴とする、請求項5に記載のアレルギー疾患の予防又は改善用健康機能食品組成物。
- 前記アレルギーは、花粉、薬物、植物繊維、細菌、食物、染毛剤、化学物質からなる群から選択される1種以上によって誘導されることを特徴とする、請求項5に記載のアレルギー疾患の予防又は改善用健康機能食品組成物。
- 前記アレルギーは、食物によって誘導されるアレルギーであることを特徴とする、請求項7に記載のアレルギー疾患の予防又は改善用健康機能食品組成物。
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China Journal of Chinese Materia Medica(中国中薬雑誌), 2011, Vol.36, No.8, pp. 1067-1070 |
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International Immunopharmacology, 2017.11.24, Vol.54, pp.286-295 |
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