JP2006513214A - 睡眠/覚醒サイクルの正規化のための化合物 - Google Patents
睡眠/覚醒サイクルの正規化のための化合物 Download PDFInfo
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- JP2006513214A JP2006513214A JP2004563786A JP2004563786A JP2006513214A JP 2006513214 A JP2006513214 A JP 2006513214A JP 2004563786 A JP2004563786 A JP 2004563786A JP 2004563786 A JP2004563786 A JP 2004563786A JP 2006513214 A JP2006513214 A JP 2006513214A
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- Prior art keywords
- sleep
- containing compound
- cytidine
- compound
- adenosine
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Abstract
Description
本発明は、睡眠/覚醒サイクルの正規化のための方法および睡眠障害の治療のための方法に関する。
本発明は概して、シチジン含有化合物、シトシン含有化合物、クレアチン含有化合物、ウリジン含有化合物、アデノシン含有化合物、またはアデノシン上昇性の化合物の治療上有効な量を哺乳類に投与することによる、哺乳類の睡眠/覚醒サイクルの正規化方法を特徴とする。この方法は、例えば、倦怠感もしくは疲労感を緩和するために、昼間の覚醒状態を高めるために、または哺乳類の睡眠の質を向上させるために使用することができる。
本明細書に記載される本発明は、睡眠/覚醒サイクルの正規化のための方法、睡眠障害の治療のための方法、および睡眠不足の哺乳類で認知機能を増加させるための方法を特徴とする。そのような正規化の効果により、個体が知覚する「睡眠の質」の改善がもたらされる可能性がある。このために、本発明は、望ましい結果をもたらすためのシチジン含有化合物、シトシン含有化合物、ウリジン含有化合物、クレアチン含有化合物、アデノシン含有化合物、およびアデノシン上昇性の化合物の使用を特徴とする。好ましいシチジン含有化合物はCDP-コリン(シチコリンまたはCDPコリン[ナトリウム塩]とも呼ばれる)であり、好ましいアデノシン含有化合物はS-アデノシルメチオニン(SAMe)であり、および好ましいウリジン含有化合物はトリアセチルウリジンである。
驚いたことに、本発明者らは、シチコリン(CDP-コリン)が睡眠/覚醒サイクルの正規化に有用であることを発見した。シチコリン治療の2週間〜4週間後、睡眠の質が改善されて、睡眠/覚醒サイクルが正規化される。この睡眠/覚醒サイクルの正規化によりさらに、覚醒状態の高まりを促進するかまたは昼間の倦怠感もしくは疲労感を緩和することができる。シチコリンの投与は同様に、不眠症、睡眠時無呼吸症(中枢性または閉塞性)、問題となる眠気、不穏下肢症候群、周期性四肢運動、および睡眠発作のような睡眠障害に関与する恒常性プロセスを安定化させる可能性が高いものと思われる。さらに、シチコリンは認知機能を増加させることができ(Alvarez et al. Methods Find Exp Clin Pharmacol 21:633-44, 1999; Fioravanti et al. Cochrane Database Syst. Rev. 4: CD000269, 2000)、睡眠不足の個体、例えば、パイロット、医師、学生、または不眠のまま長い時間を経験し得る他の者において認知動作を高めるのに使用することができる。図1のデータは、10点満点制で被験者により判断した場合、シチコリンの投与が、偽薬を投与された被験者と比べて、ヒト被験者の睡眠の質および気分を高めていることを示している。CDP-コリンは投与後、シチジンおよびコリンに素早く代謝されて、シチジンはウリジンに変換されるので、これらの化合物のいずれかを投与することは、有益な効果を有する可能性がある。
有用なシチジン含有化合物またはシトシン含有化合物としては、以下のうちの一つを含んだ任意の化合物を挙げることができる: シトシン、シチジン、CMP、CDP、CTP、dCMP、dCDP、およびdCTP。好ましいシチジン含有化合物としては、CDP-コリンおよびシチジン5'-ジホスホコリン[ナトリウム塩]が挙げられる。このシチジン含有化合物およびシトシン含有化合物の羅列は、本発明を限定するためではなく、説明するために示されており、上記の化合物は、例えば、Sigma Chemical社(St. Louis, MO)から入手することができる。
アデノシン含有化合物またはアデノシン上昇性の化合物により同様に、有用な治療法が提供される。動物実験のデータから、アデノシン類似体の投与により、徐波睡眠の量が増加することが示されている(Radulovacki M et al. J Pharmacol Exp Ther 228:268-74, 1984; Satoh S et al. Eur J Pharmacol 351:155-62, 1998; Scammell TE et al. Neuroscience 107:653-63, 2001)。さらに、磁気共鳴データから、断眠によりアデノシンの蓄積が起こることが示唆されている。この蓄積は「睡眠の圧力」に関する神経生物学的な根拠であるとすることができ、このアデノシンの蓄積により回復睡眠を可能とすることができる。従って、これらの化合物は、睡眠の恒常性の維持に不可欠な役割を果たすことができる。
ウリジンおよびウリジン含有化合物は、PC生合成の律速因子であるCTPに変換されることができるので、有用な治療法を与える(Wurtman et al., Biochemical Pharmacology 60:989-992, 2000)。有用なウリジン含有化合物としては、ウリジン、UTP、UDP、またはUMPを含んだ任意の化合物が挙げられるがこれに限定されることはない。好ましいウリジン含有化合物は、トリアセチルウリジンである。ウリジンおよびウリジン含有化合物ならびに類似体は、ヒトにおいて耐用性良好である。
クレアチンおよびクレアチン含有化合物は、脳のリン脂質レベルを増加させることにより、ATPのレベルを上昇させることができるので、有用な治療法を与える。クレアチンおよびクレアチン含有化合物は、ヒトにおいて比較的高用量で耐用性良好であることが知られている。
患者への投与に適した製剤または組成物を提供するため、従来の製薬学的実践を採用する。経口投与が好ましいが、任意の他の適当な投与経路、例えば、非経口投与、静脈内投与、皮下投与、筋肉内投与、頭蓋内投与、眼窩内投与、眼投与、脳室内投与、関節内投与、髄腔内投与、嚢内投与、腹腔内投与、鼻腔内投与、またはエアロゾル投与を採用することができる。治療用製剤は溶剤または懸濁剤の形態とすることができる(例えば、静脈内投与の場合); 経口投与の場合、製剤は液剤、錠剤、またはカプセル剤の形態とすることができる; および鼻腔内投与の場合、散剤、点鼻薬、または煙霧剤の形態とすることができる。
本発明のシチジン含有化合物、シトシン含有化合物、ウリジン含有化合物、クレアチン含有化合物、アデノシン含有化合物、およびアデノシン上昇性の化合物は、単剤療法として、お互いと併用して、または異常な睡眠/覚醒サイクルもしくは睡眠障害または他の関連する生理的症状もしくは精神的症状を治療するための他の化合物と併用して投与することができる。
本明細書に記載される全ての刊行物、特許、および特許出願は、それぞれ個別の刊行物または特許出願が具体的かつ個別に参照として組み入れられると示されるかのごとく、参照として本明細書に組み入れられる。
Claims (18)
- シチジン含有化合物、シトシン含有化合物、ウリジン含有化合物、クレアチン含有化合物、アデノシン含有化合物、およびアデノシン上昇性の化合物からなる群より選択される化合物の治療上有効な量を哺乳類に投与する段階、それにより該哺乳類の睡眠/覚醒サイクルを正規化する段階を含む、哺乳類の睡眠/覚醒サイクルの正規化方法。
- 投与により、倦怠感もしくは疲労感が減少するか、覚醒状態が高まるか、または昼間の哺乳類の睡眠の質が向上する、請求項1記載の方法。
- シチジン含有化合物がシチジンである、請求項1記載の方法。
- シチジン含有化合物がコリンをさらに含む、請求項1記載の方法。
- シチジン含有化合物がCDP-コリンである、請求項1記載の方法。
- CDP-コリンが経口的に投与される、請求項5記載の方法。
- シチジン含有化合物がCDPである、請求項1記載の方法。
- 投与段階が長期的である、請求項1記載の方法。
- 哺乳類がヒトである、請求項1記載の方法。
- ヒトが小児または青年である、請求項9記載の方法。
- ヒトが高齢者である、請求項9記載の方法。
- シチジン含有化合物、シトシン含有化合物、ウリジン含有化合物、クレアチン含有化合物、アデノシン含有化合物、およびアデノシン上昇性の化合物からなる群より選択される化合物の治療上有効な量を哺乳類に投与する段階を含む、睡眠障害の治療方法。
- 睡眠障害が物質乱用障害により引き起こされる、請求項12記載の方法。
- 物質乱用障害はアルコール、カフェイン、またはコカインの使用または依存である、請求項13記載の方法。
- 睡眠障害は不眠症、構造性もしくは閉塞性の睡眠時無呼吸症、不穏下肢症候群、周期性四肢運動(periodic limb movement)、問題となる眠気(problem sleepiness)、または睡眠発作である、請求項12記載の方法。
- シチジン含有化合物がCDP-コリンである、請求項12記載の方法。
- シチジン含有化合物、シトシン含有化合物、ウリジン含有化合物、クレアチン含有化合物、アデノシン含有化合物、およびアデノシン上昇性の化合物からなる群より選択される化合物の治療上有効な量を、睡眠遮断(sleep deprivation)で苦しむ哺乳類に投与する段階、それにより該哺乳類の認知機能を増加させる段階を含む、認知機能の増加方法。
- シチジン含有化合物はCDP-コリンである、請求項17記載の方法。
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PCT/US2003/040450 WO2004058160A2 (en) | 2002-12-20 | 2003-12-17 | Compounds for the normalization of the sleep/wake cycle |
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WO2008050853A1 (fr) * | 2006-10-26 | 2008-05-02 | Kyowa Hakko Kirin Co., Ltd. | Agents therapeutiques pour lutter contre le syndrome du colon irritable |
JP2010248161A (ja) * | 2009-04-20 | 2010-11-04 | Ito En Ltd | ウリジンを含有する抗疲労剤又は体力向上剤 |
JP2011502539A (ja) * | 2007-11-16 | 2011-01-27 | バイオ クリニカル デベロップメント,インコーポレイテッド | 低カフェイン可食性活力組成物 |
JP2011032232A (ja) * | 2009-08-04 | 2011-02-17 | Ito En Ltd | 興奮抑制用又は鎮静用組成物及びこれを含む飲食品 |
WO2013051728A1 (ja) | 2011-10-06 | 2013-04-11 | ライオン株式会社 | 睡眠の質改善剤 |
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EP1565055B1 (en) * | 2002-11-08 | 2013-06-12 | THE McLEAN HOSPITAL CORPORATION | Compounds for the treatment of tobacco dependence and withdrawal |
US20050113449A1 (en) * | 2003-10-08 | 2005-05-26 | Renshaw Perry F. | Enhanced efficacy of omega-3 fatty acid therapy in the treatment of psychiatric disorders and other indications |
CA2542023A1 (en) * | 2003-10-08 | 2005-09-22 | The Mclean Hospital Corporation | Methods of treating psychiatric, substance abuse, and other disorders using combinations containing omega-3 fatty acids |
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PL1888081T3 (pl) * | 2005-05-23 | 2017-07-31 | Massachusetts Institute Of Technology | Kompozycje zawierające PUFA i sposoby ich zastosowania |
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JP4717444B2 (ja) | 2011-07-06 |
RU2005122934A (ru) | 2006-01-20 |
MXPA05006781A (es) | 2005-09-30 |
US20040176316A1 (en) | 2004-09-09 |
EP1589979A2 (en) | 2005-11-02 |
JP2011102319A (ja) | 2011-05-26 |
BR0317586A (pt) | 2005-11-22 |
CN100563660C (zh) | 2009-12-02 |
EP1589979A4 (en) | 2009-04-01 |
CN1750833A (zh) | 2006-03-22 |
CA2508995A1 (en) | 2004-07-15 |
RU2366428C2 (ru) | 2009-09-10 |
AU2003299715A8 (en) | 2004-07-22 |
WO2004058160A3 (en) | 2005-03-31 |
NO20052987L (no) | 2005-08-29 |
NO20052987D0 (no) | 2005-06-17 |
UA88869C2 (ru) | 2009-12-10 |
WO2004058160A2 (en) | 2004-07-15 |
AU2003299715A1 (en) | 2004-07-22 |
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