JP2020523294A - 新規なクエルセチン系化合物を含む抗炎症組成物 - Google Patents
新規なクエルセチン系化合物を含む抗炎症組成物 Download PDFInfo
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
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- A—HUMAN NECESSITIES
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
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- A—HUMAN NECESSITIES
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- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
Description
緑茶(Camellia sinensis var. Yabukita)葉で作った緑茶に水を添加して水分含量を40重量%に調整した。これにバチルス・サブチリス(Bacillus subtillis)5×106cfu/gを接種し、50℃で3日間醗酵させた後に80℃で4日間醗酵させた。
前記後発酵茶試料150gをアセトンで分画してカテキン誘導体及びカフェインを除去し、他の化合物が濃縮された可溶物を収得した。前記アセトン可溶物40gに対し一次的にシリカゲルコラムクロマトグラフィーを利用して、クロロホルム:メタノールの5:1(v/v)混合物を溶媒として分画物を得た。
ヒト線維芽細胞(fibroblast)(PromoCell、Germany)を6ウェル培養板に1×105細胞の濃度で接種し、24時間、37℃、5%CO2インキュベーターで培養した。H2O2 500μMをウェルに処理し、24時間刺激を与えた後、クエルセチン3−O−[3−O”−(E)−p−クマロイル][β−D−グルコピラノシル−(1→3)−O−α−L−ラムノピラノシル−(1→6)−O−β−D−グルコピラノシド](「新規物質31」)と、クエルセチン3−O−[3−O”−(E)−p−クマロイル][α−L−ラムノピラノシル−(1→6)−O−β−D−グルコピラノシド](「新規物質32」)をそれぞれ100μg/mlの濃度で処理し、48時間反応させた。反応完了後、培養液を収去してELISA分析を行った。このとき、抗炎症及び刺激緩和剤として多用される物質であるα−ビサボロール(α−bisabolol)を対照群として用いた。PGE2は、アッセイデザイン(Assay Design)社製のキット、IL−6、IL−8はエンドジェン(Endogen)社製のキットを用い、各会社のマニュアルに明記された方法に従い実験を進行した。抑制効果は下記の数学式1によって求め、その測定結果を下記の表3に表した。(「31」は新規物質31を意味し、「32」は新規物質32を意味する)
クエルセチン3−O−[3−O”−(E)−p−クマロイル][β−D−グルコピラノシル−(1→3)−O−α−L−ラムノピラノシル−(1→6)−O−β−D−グルコピラノシド]と、クエルセチン3−O−[3-O”−(E)−p−クマロイル][α−L−ラムノピラノシル−(1→6)−O−β−D−グルコピラノシド]の皮膚累積刺激性の有無を確認し、皮膚に使用できる濃度範囲を算出するために、HRIPT(Human repeated insult patch tests)を実施した。
クエルセチン3−O−[3−O”−(E)−p−クマロイル][β−D−グルコピラノシル−(1→3)−O−α−L−ラムノピラノシル−(1→6)−O−β−D−グルコピラノシド]又はクエルセチン3−O−[3−O”−(E)−p−クマロイル][α−L−ラムノピラノシル−(1→6)−O−β−D−グルコピラノシド]10mg、L−カルニチン80〜140mg、大豆油180mg、パーム油2mg、植物性硬化油8mg、黄蝋4mg及びレシチン6mgを混合し、通常の方法に従い1カプセルに充填して軟質カプセル剤を製造した。
クエルセチン3−O−[3−O”−(E)−p−クマロイル][β−D−グルコピラノシル−(1→3)−O−α−L−ラムノピラノシル−(1→6)−O−β−D−グルコピラノシド]又はクエルセチン3−O−[3−O”−(E)−p−クマロイル][α−L−ラムノピラノシル−(1→6)−O−β−D−グルコピラノシド]10mg、ガラクトオリゴ糖200mg、乳糖60mg及び麦芽糖140mgを混合し、流動層乾燥機を用いて顆粒化した後、糖エステル(sugar ester)6mgを添加して、打錠機で打錠して錠剤を製造した。
クエルセチン3−O−[3−O”−(E)−p−クマロイル][β−D−グルコピラノシル−(1→3)−O−α−L−ラムノピラノシル−(1→6)−O−β−D−グルコピラノシド]又はクエルセチン3−O−[3−O”−(E)−p−クマロイル][α−L−ラムノピラノシル−(1→6)−O−β−D−グルコピラノシド]5mg、無水結晶ブドウ糖250mg及び澱粉550mgを混合し、流動層造粒機を用いて顆粒に成形した後、包に充填して顆粒剤を製造した。
クエルセチン3−O−[3−O”−(E)−p−クマロイル][β−D−グルコピラノシル−(1→3)−O−α−L−ラムノピラノシル−(1→6)−O−β−D−グルコピラノシド]又はクエルセチン3−O−[3−O”−(E)−p−クマロイル][α−L−ラムノピラノシル−(1→6)−O−β−D−グルコピラノシド]2mg、ブドウ糖10g、クエン酸0.6g、及び液状オリゴ糖25gを混合した後、精製水300mlを加えて各瓶に200mlずつ充填する。瓶に充填した後、130℃で4〜5秒間殺菌してドリンク剤を製造した。
クエルセチン3−O−[3−O”−(E)−p−クマロイル][β−D−グルコピラノシル−(1→3)−O−α−L−ラムノピラノシル−(1→6)−O−β−D−グルコピラノシド]又はクエルセチン3−O−[3−O”−(E)−p−クマロイル][α−L−ラムノピラノシル−(1→6)−O−β−D−グルコピラノシド]20mg、適量の注射用滅菌蒸留水、適量のpH調節剤を用いて通常の方法に従い注射剤を製造した。
下記の表5に記載された組成にて通常の方法に従い健康食品を製造した。
クエルセチン3−O−[3−O”−(E)−p−クマロイル][β−D−グルコピラノシル−(1→3)−O−α−L−ラムノピラノシル−(1→6)−O−β−D−グルコピラノシド]又はクエルセチン3−O−[3−O”−(E)−p−クマロイル][α−L−ラムノピラノシル−(1→6)−O−β−D−グルコピラノシド]0.2重量%、L−アスコルビン酸−2−リン酸マグネシウム塩1.00重量%、水溶性コラーゲン(1%水溶液)5.00重量%、クエン酸ナトリウム0.10重量%、クエン酸0.05重量%、甘草エキス0.20重量%、1,3−ブチレングリコール3.00重量%、残量として精製水を用いて柔軟化粧水(スキンローション)を製造した。
クエルセチン3−O−[3−O”−(E)−p−クマロイル][β−D−グルコピラノシル−(1→3)−O−α−L−ラムノピラノシル−(1→6)−O−β−D−グルコピラノシド]又はクエルセチン3−O−[3−O”−(E)−p−クマロイル][α−L−ラムノピラノシル−(1→6)−O−β−D−グルコピラノシド]0.2重量%、ポリエチレングリコールモノステアレート2.00重量%、自己乳化型モノステアリン酸グリセリン5.00重量%、プロピレングリコール4.00重量%、スクアレン6.00重量%、トリ2−エチルヘキサングリセリル6.00重量%、スフィンゴ糖脂質1.00重量%、1,3−ブチレングリコール7.00重量%、蜜蝋5.00重量%、残量として精製水を用いてクリーム状製剤を製造した。
クエルセチン3−O−[3−O”−(E)−p−クマロイル][β−D−グルコピラノシル−(1→3)−O−α−L−ラムノピラノシル−(1→6)−O−β−D−グルコピラノシド]又はクエルセチン3−O−[3−O”−(E)−p−クマロイル][α−L−ラムノピラノシル−(1→6)−O−β−D−グルコピラノシド]0.2重量%、ポリビニルアルコール21.00重量%、L−アスコルビン酸−2−リン酸マグネシウム塩3.00重量%、ラウロイルヒドロキシプロリン5.00重量%、水溶性コラーゲン(1%水溶液)8.00重量%、1,3−ブチレングリコール7.00重量%、エタノール7.00重量%、残量として精製水を用いて組成物を製造し、これを用いてパックを製造した。
Claims (16)
- 下記の化学式1で表される化合物、その光学異性体、その薬学的に許容可能な塩、その水和物、その溶媒和物、又はこれを含む後発酵茶抽出物を有効成分として含む抗炎症組成物。
- 前記R1は下記の化学式2で表される、請求項1に記載の抗炎症組成物。
- 前記R2は下記の化学式3で表される、請求項1に記載の抗炎症組成物。
- 前記R3は下記の化学式4で表される、請求項1に記載の抗炎症組成物。
- 前記化合物は、クエルセチン3−O−[3−O”−(E)−p−クマロイル][β−D−グルコピラノシル−(1→3)−O−α−L−ラムノピラノシル−(1→6)−O−β−D−グルコピラノシド](Quercetin3−O−[3−O”−(E)−p−coumaroyl][β−D−glucopyranosyl−(1→3)−O−α−L−rhamnopyranosyl−(1→6)−O−β−D−glucopyranoside])である、請求項1に記載の抗炎症組成物。
- 前記化合物は、クエルセチン3−O−[3−O”−(E)−p−クマロイル][α−L−ラムノピラノシル−(1→6)−O−β−D−グルコピラノシド](Quercetin3−O−[3−O”−(E)−p−coumaroyl][α−L−rhamnopyranosyl−(1→6)−O−β−D−glucopyranoside])である、請求項1に記載の抗炎症組成物。
- 前記抽出は、熱水、C1〜C6の低級アルコール、及びこれらの混合溶媒から選ばれた一種以上の溶媒による抽出である、請求項1に記載の抗炎症組成物。
- 前記低級アルコールはエタノールである、請求項7に記載の抗炎症組成物。
- 前記抽出物は、抽出後にケトンで分画した分画物である、請求項1に記載の抗炎症組成物。
- 前記ケトンはアセトンである、請求項9に記載の抗炎症組成物。
- 前記組成物中の化学式1で表される化合物、その光学異性体、その薬学的に許容可能な塩、その水和物、又はその溶媒和物の含量は、前記組成物の総重量に対し、0.00001重量%〜10重量%の範囲である、請求項1に記載の抗炎症組成物。
- 前記組成物中の後発酵茶抽出物の含量は、前記組成物の総重量に対し、0.1重量%〜90重量%の範囲である、請求項1に記載の抗炎症組成物。
- 前記抽出物は、前記化学式1で表される化合物、その光学異性体、その薬学的に許容可能な塩、その水和物、又はその溶媒和物が、抽出物の総重量を基準に、0.00001重量%〜20重量%の範囲で含まれたものである、請求項1に記載の抗炎症組成物。
- 前記組成物の投与による前記化学式1で表される化合物、その光学異性体、その薬学的に許容可能な塩、その水和物、又はその溶媒和物の投与量は、0.00001mg/kg/日〜100mg/kg/日の範囲である、請求項1に記載の抗炎症組成物。
- 前記組成物は、PGE2(Prostaglandin E2)、IL−6(Interleukin 6)及びIL−8(Interleukin 8)からなる群より選ばれる一種以上の生成を抑制する、請求項1〜14のいずれか一項に記載の抗炎症組成物。
- 前記組成物は、食品組成物、化粧料組成物、又は薬学組成物である、請求項1〜14のいずれか一項に記載の抗炎症組成物。
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