JP6095615B2 - 器質的脳障害に起因する高次脳機能の低下に対する改善作用を有する組成物 - Google Patents
器質的脳障害に起因する高次脳機能の低下に対する改善作用を有する組成物 Download PDFInfo
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- JP6095615B2 JP6095615B2 JP2014149230A JP2014149230A JP6095615B2 JP 6095615 B2 JP6095615 B2 JP 6095615B2 JP 2014149230 A JP2014149230 A JP 2014149230A JP 2014149230 A JP2014149230 A JP 2014149230A JP 6095615 B2 JP6095615 B2 JP 6095615B2
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- docosahexaenoic
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Images
Description
したがって、器質的脳障害による高次脳機能の低下を改善又は向上させ、医薬、さらには食品への適応に優れた副作用の少ない化合物の開発が強く望まれている。
本発明の組成物を医薬品として使用する場合、組成物中の有効成分の配分量は、本発明の目的が達成される限り特に限定されず、適宜適当な配合割合で使用が可能である。
本発明の組成物を医薬品として使用する場合、投与単位形態で投与するのが望ましく、特に、経口投与が好ましい。
実施例1. アラキドン酸を構成脂肪酸とするトリグリセリドの製造方法
アラキドン酸生産菌としてモルティエレラ・アルピナ(Mortierella alpina)を用いた。グルコース1.8%、脱脂大豆粉3.1%、大豆油1.2%、KH2PO4 0.3%、Na2SO4 0.1%、CaCl2・2H2O 0.05%及びMgCl2・6H2O 0.05%を含む培地6kLを、10kL培養槽に調製し、初発pHを6.0に調整した。前培養液30Lを接種し、温度26℃、通気量 360m3/h、槽内圧200kPaの条件で8日間の通気撹拌培養を行った。なお、攪拌数は溶存酸素濃度を10-15ppmを維持するように調整した。さらに、グルコース濃度を4日目までは流加法によって培地中のグルコース濃度が1-2.5%の範囲内となるように、それ以降は0.5-1%を維持した(上記の%は、重量(W/V)%を意味する)。
ゼラチン100重量部及び食添グリセリン35重量部に水を加え50〜60℃で溶解し、粘度2000cpのゼラチン被膜を調製した。次に実施例1で得たアラキドン酸含有油脂(トリグリセリド)60重量%と魚油(ツナ油:全脂肪酸に占めるドコサヘキサエン酸の割合は、40.5%)40重量%で混合し、ビタミンE油0.05重量%を混合して内容物1を調製した。これら内容物1を用いて、常法によりカプセル成形及び乾燥を行い、一粒240mgの内容物を含有するソフトカプセルを製造した。人試験用の擬似カプセルとして、内容物をオリーブ油(オリーブ油に対してビタミンE油0.05重量%を混合)としたソフトカプセルを同時に製造した。
RBANS神経心理テスト(Repeatable Battery for the Assessment of Neuropsychological Status)は、その開発者であるRandolphの方法[J Clin Exp Neuropsychol Vol.20 310-319 (1998)]を日本語訳した日本版アーバンス神経心理テスト[脳神経 Vol.54 463-471 (2002)]を用いた。すなわち、即時記憶、視空間・構成、言語、注意および遅延記憶の5つの認知領域について、12の下位検査により評価した。なお、本発明のヒト試験は、ヘルシンキ宣言の精神に則り十分な配慮の下に実施した。
このように、アラキドン酸およびドコサヘキサエン酸含有食用油脂を服用することで器質的脳障害に起因する高次脳機能の低下を改善することを初めて明らかにした。
実施例1で得たアラキドン酸含有油脂(トリグリセリド)200g、魚油を精製したドコサヘキサエン酸含有油脂(トリグリセリド)200g、精製卵黄レシチン48g、オレイン酸20g、グリセリン100g及び0.1N 苛性ソーダ40mlを加え、ホモジナイザーで分散させたのち、注射用蒸留水を加えて4リットルとする。これを高圧噴霧式乳化機にて乳化し、脂質乳液を調製した。該脂質乳液を200mlずつプラスチック製バッグに分注したのち、121℃、20分間、高圧蒸気滅菌処理して脂肪輸液剤とする。
β-シクロデキストリン2gを20%エタノール水溶液20mlに添加し、ここにスターラーで撹拌しながら、実施例1で得たアラキドン酸含有油脂(トリグリセリド)と魚油を精製したドコサヘキサエン酸含有油脂(トリグリセリド)の混合液(ビタミンEを0.05%配合)100mgを加え、50℃で2時間インキュベートした。室温冷却(約1時間)後、さらに撹拌を続けながら4℃で10時間インキュベートした。生成した沈殿を、遠心分離により回収し、n-ヘキサンで洗浄後、凍結乾燥を行い、アラキドン酸およびドコサヘキサエン酸含有トリグリセリドを含有するシクロデキストリン包接化合物1.8gを得た。この粉末1gをジュース10Lに均一に混ぜ合わせ、アラキドン酸およびドコサヘキサエン酸含有トリグリセリドを含有するジュースを調製した。
ゼラチン100重量部及び食添グリセリン35重量部に水を加え50〜60℃で溶解し、粘度2000cpのゼラチン被膜を調製した。次に実施例1で得たアラキドン酸含有油脂(トリグリセリド)にビタミンE油0.05重量%を混合し、内容物2を調製した。実施例1で得た99%アラキドン酸エチルエステルに、ビタミンE油0.05重量%を混合し内容物3を調製した。これら内容物2から3を用いて、常法によりカプセル成形及び乾燥を行い、一粒当たり180mgの内容物を含有するソフトカプセルを製造した。
Claims (4)
- アラキドン酸を構成脂肪酸とするトリグリセリド及びドコサヘキサエン酸を構成脂肪酸とするトリグリセリドを含んでなる、ヒトに対してアラキドン酸及びドコサヘキサエン酸を経口投与するための、脳挫傷又は脳梗塞に基因するアーバンス神経心理テストにより測定される高次脳機能障害における即時記憶又は遅延記憶の低下に対する改善用飲食物。
- 前記アラキドン酸とドコサヘキサエン酸との組み合せにおいて、アラキドン酸/ドコサヘキサエン酸比(重量)が0.1〜15の範囲にある、請求項1に記載の飲食物。
- 経腸栄養剤、粉末、顆粒、トローチ、内服液、懸濁液、乳濁液、シロップ又はカプセル剤の形態である、請求項1又は2に記載の飲食物。
- 機能性食品、栄養補助食品、特定保健用食品又は老人用食品である、請求項1〜3のいずれか1項に記載の飲食物。
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