JP2009001564A - 抗鬱・抗ストレス組成物 - Google Patents
抗鬱・抗ストレス組成物 Download PDFInfo
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- JP2009001564A JP2009001564A JP2008151136A JP2008151136A JP2009001564A JP 2009001564 A JP2009001564 A JP 2009001564A JP 2008151136 A JP2008151136 A JP 2008151136A JP 2008151136 A JP2008151136 A JP 2008151136A JP 2009001564 A JP2009001564 A JP 2009001564A
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- tryptamine
- acid
- acyl derivative
- indol
- ethyl
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- 230000002180 anti-stress Effects 0.000 title claims abstract description 25
- 239000000203 mixture Substances 0.000 title claims abstract description 20
- APJYDQYYACXCRM-UHFFFAOYSA-N Tryptamine Natural products C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 claims abstract description 70
- 150000001875 compounds Chemical class 0.000 claims abstract description 7
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 7
- 229930195734 saturated hydrocarbon Natural products 0.000 claims abstract description 7
- 239000012453 solvate Substances 0.000 claims abstract description 7
- 229930195735 unsaturated hydrocarbon Natural products 0.000 claims abstract description 7
- 244000299461 Theobroma cacao Species 0.000 claims description 31
- 239000000935 antidepressant agent Substances 0.000 claims description 26
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- 229940005513 antidepressants Drugs 0.000 claims description 25
- NVUGEQAEQJTCIX-UHFFFAOYSA-N N-acetyltryptamine Chemical compound C1=CC=C2C(CCNC(=O)C)=CNC2=C1 NVUGEQAEQJTCIX-UHFFFAOYSA-N 0.000 claims description 20
- HAWFHRQOMIMGFR-UHFFFAOYSA-N N-[2-(1H-Indol-3-yl)ethyl]docosanamide Chemical compound C1=CC=C2C(CCNC(=O)CCCCCCCCCCCCCCCCCCCCC)=CNC2=C1 HAWFHRQOMIMGFR-UHFFFAOYSA-N 0.000 claims description 18
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 claims description 18
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 claims description 18
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Abstract
Description
トリプタミンのN−アシル誘導体の合成方法
各種トリプタミンのN−アシル誘導体は、トリプタミンと各種脂肪酸の塩化物を縮合させることにより容易に合成することが可能である。また脂肪酸の種類を替えることにより任意のトリプタミンのN−アシル誘導体を合成することができる。具体例としてN−リグノセロイルトリプタミン(tetraeicosanoic
acid [2-(1H-indol-3-yl) ethyl] amide)の合成方法を以下に示した。トリプタミンの塩酸塩(2mmol)、トリエチルアミン(2mmol)、塩化リグノセリン酸(2mmol)を10mlのクロロホルム中で2時間室温で反応させた。反応液に水10ml、クロロホルム10mlを加え抽出を行い、クロロホルム層を飽和食塩水で3回洗浄し、さらに無水硫酸ナトリウムで水分を除いた。クロロホルム層を減圧濃縮し、析出物をアセトンで再結晶することによりN−リグノセロイルトリプタミンを得た(収率75%)。以下にN−リグノセロイルトリプタミンの融点及び1H-NMRデータを示した。
融点:120℃
1H-NMR (CDCl3) : δ 8.05 (1H, brs), 7.61 (1H, d, J=7.6Hz), 7.38 (1H, d, J=7.6Hz), 7.21 (1H, t, J=7.6Hz), 7.13 (1H, t, J=7.6Hz), 7.04 (1H, d, J=1.8Hz), 5.47 (1H, brs), 3.62 (2H, m), 2.98 (2H, t, J=6.4Hz), 2.09 (2H, t, J=7.6), 1.56 (2H, m), 1.26 (42H, brs), 0.88 (3H, t, J=6.6Hz)
トリプタミンのN−アシル誘導体の天然物からの抽出精製例
粉砕したカカオ豆の皮(カカオハスク)100gをジエチルエーテルで2時間ソックスレー抽出を行った。抽出液を濃縮、乾燥後シリカゲルカラムに負荷し、ベンゼン/ジエチルエーテル(6:4v/v)でトリアシルグリセライド類を除去した。次にジエチルエーテル400mlで溶出させ、溶出液を濃縮後、HPLCによる精製を行った。ODSシリカゲルカラムを用い、アセトニトリル/THF/水(90:7:3v/v)で溶出させ、蛍光検出器(励起波長281nm、測定波長330nm)でモニターしながら、検出されるピークを分取した。各フラクションを濃縮し、適宜再結晶等を行うことによりトリプタミンのN−アシル誘導体を得た(カカオハスクからはN−リグノセロイルトリプタミン、N−ベヘノイルトリプタミンが主要成分として得られる)。これらの抽出精製方法の詳細についてはZ Levensm Unters Forsch A, 208, 39-46 (1999)に記述されている。
マウス強制水泳試験による精神安定作用の評価
本発明の抗鬱及び抗ストレス作用を評価する方法として、向精神薬のスクリーニング法として1977年にPorsoltにより開発されたマウス強制水泳試験を採用した。本試験は鬱病の動物モデル実験として最も多用される方法のひとつである。本試験では、マウスをある限られたスペースの中で強制的に泳がせて「無動状態」を惹起させる。この無動状態は、ストレスを負荷された動物が水からの逃避を放棄した一種の「絶望状態」を反映するものと考えられ、ヒトにおける鬱状態、ストレス状態と関連づけられている。事実、抗鬱薬は特異的にこの状況下における無動状態の持続時間を短縮させることがわかっており、この短縮作用は臨床力価との間に有意な相関を有することが認められている。
〈散剤〉
乳糖 60部
馬鈴薯でんぷん 30部
N−リグノセロイルトリプタミン 10部
〈錠剤〉
D−マンニトール 40部
乳糖 35部
結晶セルロース 10部
N−アセチルトリプタミン 10部
ヒドロキシプロピルセルロース 5部
〈チョコレート〉
粉糖 41.8部
カカオビター 20部
全脂粉乳 20部
カカオバター 17部
N−オレイルトリプタミン 1部
香料 0.2部
〈キャンディ〉
グラニュー糖 50部
水飴 33部
クエン酸 2部
N−リグノセロイルトリプタミン 0.5部
香料 0.2部
水 14.3部
〈チューインガム〉
粉糖 54部
ガムベース 20部
水飴 14.5部
ブドウ糖 10部
香料 1部
N−ベヘノイルトリプタミン 0.5部
Claims (6)
- Rが、CH3(N−アセチルトリプタミン:ethanoic acid[2-(1H-indol-3-yl) ethyl] amide)、C17H33(N−オレイルトリプタミン:9-octadecenoic acid [2-(1H-indol-3-yl) ethyl] amide)、C21H43(N−ベヘノイルトリプタミン:doeicosanoic acid [2-(1H-indol-3-yl) ethyl] amide)、C23H47(N−リグノセロイルトリプタミン:tetraeicosanoic acid [2-(1H-indol-3-yl) ethyl] amide)であるトリプタミンのN−アシル誘導体であることを特徴とする請求項1〜4のいずれかに記載の抗鬱・抗ストレス組成物。
- トリプタミンのN−アシル誘導体を0.5重量%以上含有する請求項1〜5のいずれかに記載の抗鬱・抗ストレス組成物。
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
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US7794965B2 (en) | 2002-03-13 | 2010-09-14 | Signum Biosciences, Inc. | Method of identifying modulators of PP2A methylase |
US7923041B2 (en) | 2005-02-03 | 2011-04-12 | Signum Biosciences, Inc. | Compositions and methods for enhancing cognitive function |
US8221804B2 (en) | 2005-02-03 | 2012-07-17 | Signum Biosciences, Inc. | Compositions and methods for enhancing cognitive function |
US9486441B2 (en) | 2008-04-21 | 2016-11-08 | Signum Biosciences, Inc. | Compounds, compositions and methods for making the same |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
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JPH09206026A (ja) * | 1996-02-08 | 1997-08-12 | Meiji Seika Kaisha Ltd | ストレスの予防および適応形成を促進させる飲食品 |
JPH09227393A (ja) * | 1996-02-28 | 1997-09-02 | Lotte Co Ltd | 精神安定性素材及び食品 |
JP2001069946A (ja) * | 1999-09-03 | 2001-03-21 | Meiji Seika Kaisha Ltd | 更年期障害を改善する飲食品 |
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2008
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JPH09206026A (ja) * | 1996-02-08 | 1997-08-12 | Meiji Seika Kaisha Ltd | ストレスの予防および適応形成を促進させる飲食品 |
JPH09227393A (ja) * | 1996-02-28 | 1997-09-02 | Lotte Co Ltd | 精神安定性素材及び食品 |
JP2001069946A (ja) * | 1999-09-03 | 2001-03-21 | Meiji Seika Kaisha Ltd | 更年期障害を改善する飲食品 |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7794965B2 (en) | 2002-03-13 | 2010-09-14 | Signum Biosciences, Inc. | Method of identifying modulators of PP2A methylase |
US7923041B2 (en) | 2005-02-03 | 2011-04-12 | Signum Biosciences, Inc. | Compositions and methods for enhancing cognitive function |
US8221804B2 (en) | 2005-02-03 | 2012-07-17 | Signum Biosciences, Inc. | Compositions and methods for enhancing cognitive function |
US9486441B2 (en) | 2008-04-21 | 2016-11-08 | Signum Biosciences, Inc. | Compounds, compositions and methods for making the same |
US10583119B2 (en) | 2008-04-21 | 2020-03-10 | Signum Biosciences, Inc. | Compounds, compositions and methods for making the same |
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