JP6672264B2 - 過眠症を治療するための方法 - Google Patents
過眠症を治療するための方法 Download PDFInfo
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- JP6672264B2 JP6672264B2 JP2017506256A JP2017506256A JP6672264B2 JP 6672264 B2 JP6672264 B2 JP 6672264B2 JP 2017506256 A JP2017506256 A JP 2017506256A JP 2017506256 A JP2017506256 A JP 2017506256A JP 6672264 B2 JP6672264 B2 JP 6672264B2
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Description
ペンチレンテトラゾール(PTZ)の投与により、対象において過眠症を治療するための方法、ならびに、過眠症を治療するために有益な、製剤および投与計画が、本明細書中に提供されている。
過眠症は、人口の約5%を襲い、例えば自動車を操作する能力、社会活動を行う能力、または仕事を維持する能力を阻害することによって、罹患した個人を苦しめ得る。過眠症は、日中の過剰な眠気(EDS)によって特徴づけられる障害である。大雑把な分類では、原発性過眠症および続発性過眠症がある。原発性過眠症は、睡眠および覚醒を調節する個人の脳の機能に伴う問題に起因する、と確信されている。原発性過眠症は、他の基礎疾患または他の基礎的な健康状態に関係なく生じる、と考えられている。続発性過眠症は、夜間の睡眠に伴う問題、十分な睡眠を得ることができないこと、または、眠気という結果を招く他の医学上の問題、によって引き起こされると確信されている。夜間の睡眠に伴う問題、十分な睡眠を得ることができないこと、または、眠気という結果を招く他の医学上の問題は、例えば、感染症、うつ病、腎不全、慢性疲労症候群、ならびに、パーキンソン病および筋強直性ジストロフィーのような神経変性病を、含む。過眠症のより具体的な分類は、例えば、睡眠障害国際分類第2版(ICSD−2)(American Academy of Sleep Medicine, Westchester IL 2005)および精神障害の診断と統計マニュアル第5版(DSM−V)(American Psychiatric Association, Washington DC 2013)を含む。過眠症の臨床的特徴を記載している他の出版物は、例えば、Ali et al., 2009, J. Clin. Sleep Med. 5, 562-568、Harris et al., 2012, Neurol. Clin. 30, 1027-1044、である。
対象において過眠症を治療するための方法が本明細書中に提供されており、上記方法は、過眠症を有する上記対象に、ペンチレンテトラゾール(PTZ)を投与することを含み、ここでは、上記投与は上記過眠症を治療するために有効である。
本明細書において用いられるとき、用語「薬学的に許容可能な」とは、薬学的組成物または薬学的製剤の、他の含有物と両立可能である成分、および、対象の組織との接触において使用に適している成分であり、必要以上の毒性、炎症、アレルギー反応、免疫原性または他の合併症を伴わず、相応の、利益/危険度の比率、と釣り合った成分、を表している。
一態様において、対象において過眠症を治療するための方法が本明細書中に提供されており、上記方法は、過眠症を有する上記対象に、GABAA塩素イオンチャネル遮断薬を投与することを含み、ここでは、上記投与は上記過眠症を治療するために有効である。
GABAA塩素イオンチャネル遮断薬は、眠気の望ましい改善という結果を招くことが可能である任意の簡便な手段、を用いて対象に投与されてもよい。投与の経路は、経口の、直腸の、非経口の、静脈内の、頭蓋内の、腹腔内の、皮内の、経皮的な、髄膜下の、鼻腔内の、気管内の(intracheal)、毛細血管内の(intracapillary)、皮下の(subcutaneous)、真皮下の(subdermal)、局所の、筋内の、直腸の、鼻の、吸入の、膣の経路、脳脊髄液の中への注入、空洞内の中への注入、または脳の中への直接の注入、を含むが、これらに限定されない。経口投与は、例えば、口内の、舌の、または舌下の投与、を含み得る。経皮的投与は、例えば、局所投与を含み得る。ニューロンの阻害を減少することが可能である化合物は、投与後に全身性であってもよく、または、局部的な投与の使用、壁内(intramural)投与の使用、もしくは、埋め込みの場所において活性投与量を保つために働く埋没物の使用、によって局部的であってもよい。ドラッグ・デリバリーのための方法の、簡潔な総説のために、例えば、Langer 1990 Science 249:1527-1533を参照せよ。
過眠症を有するヒトの患者にPTZを投与することによる、過眠症の治療を、この予言的実施例に記載する。
過眠症を有するヒトの患者にPTZを投与することによる、過眠症の治療を、この実施例に記載する。
過眠症を有し、かつ、PTZの投与に先立って、フルマゼニル(患者1)またはクラリスロマイシン(患者2)の投与で治療した二人のヒトの患者に、PTZを投与することによる、過眠症の治療を、この実施例に記載する。
Claims (34)
- 対象において特発性過眠症を治療するための、ペンチレンテトラゾール(PTZ)を含む薬学的組成物。
- 上記PTZは、少なくとも毎日一度、少なくとも五日間連続で投与されるものである、請求項1の薬学的組成物。
- 上記PTZは、一日一度、一日二度、一日三度、または一日四度投与されるものである、請求項1の薬学的組成物。
- 上記PTZは、約1mgから1,500mgの投与量で投与されるものである、請求項1の薬学的組成物。
- 上記PTZは、約5mgから1,000mgの投与量で投与されるものである、請求項1の薬学的組成物。
- 上記PTZは、約10mgから800mgの投与量で投与されるものである、請求項1の薬学的組成物。
- 上記PTZは、約25mgから600mgの投与量で投与されるものである、請求項1の薬学的組成物。
- 上記PTZは、約25から25,000ng/mlの平均Cmaxを達成するために十分な投与量で投与されるものである、請求項1の薬学的組成物。
- 上記PTZは、約50から20,000ng/mlの平均Cmaxを達成するために十分な投与量で投与されるものである、請求項1の薬学的組成物。
- 上記PTZは、約100から15,000ng/mlの平均Cmaxを達成するために十分な投与量で投与されるものである、請求項1の薬学的組成物。
- 上記PTZは、約500から10,000ng/mlの平均Cmaxを達成するために十分な投与量で投与されるものである、請求項1の薬学的組成物。
- 上記PTZは、約1,000から8,000ng/mlの平均Cmaxを達成するために十分な投与量で投与されるものである、請求項1の薬学的組成物。
- 上記PTZは、約3,000から6,000ng/mlの平均Cmaxを達成するために十分な投与量で投与されるものである、請求項1の薬学的組成物。
- 上記PTZは、上記対象の夜間の睡眠に先立って、または、上記対象の夜間の睡眠の間に投与されるものである、請求項1の薬学的組成物。
- 上記PTZは、上記対象の朝の目覚めの期間に先立って、または、上記対象の朝の目覚めの期間に投与されるものである、請求項1の薬学的組成物。
- 上記Cmaxは、脳において達成される、請求項1の薬学的組成物。
- 上記PTZは、経口製剤で投与されるものである、請求項1の薬学的組成物。
- 上記PTZは、遅延放出製剤で投与されるものである、請求項1の薬学的組成物。
- 上記遅延放出製剤は、投与の時間から、30分後から12時間後まで、脳におけるPTZの最高濃度を延期する、請求項18の薬学的組成物。
- 上記遅延放出製剤は、上記対象の夜間の睡眠の間に、または、上記対象の朝の目覚めの期間に、PTZを放出する、請求項18の薬学的組成物。
- 上記PTZは、持続放出製剤で投与されるものである、請求項1の薬学的組成物。
- 上記持続放出製剤は、投与後、30分間から12時間、上記PTZの治療的有効投与量を維持する、請求項21の薬学的組成物。
- 上記PTZは、約500ng*hr/mLから150,000ng*hr/mLのAUCを達成するために調剤される、請求項1の薬学的組成物。
- 上記PTZは、約1,000ng*hr/mLから100,000ng*hr/mLのAUCを達成するために調剤される、請求項1の薬学的組成物。
- 上記PTZは、約5,000ng*hr/mLから50,000ng*hr/mLのAUCを達成するために調剤される、請求項1の薬学的組成物。
- 上記PTZは、約10,000ng*hr/mLから20,000ng*hr/mLのAUCを達成するために調剤される、請求項1の薬学的組成物。
- 上記PTZは、約1,000ng*hr/mLから50,000ng*hr/mLのAUCを達成するために調剤される、請求項1の薬学的組成物。
- 上記対象はヒトである、請求項1の薬学的組成物。
- 上記特発性過眠症を有する上記対象の脳脊髄液(CSF)は、上記特発性過眠症を有さない対象の上記CSFと相対的に、高水準の内在性ポジティブGABAA受容体アロステリック調節物質を含む、請求項1の薬学的組成物。
- 上記特発性過眠症候群(hypersomnia symdrome)は、上記対象における内在性ポジティブアロステリックGABAA受容体調節物質によって仲介される、請求項1の薬学的組成物。
- 特発性過眠症を有する上記対象は、スタンフォード眠気尺度(SSS)、エプワース眠気尺度(ESS)、睡眠潜時反復(MSL)検査、覚醒維持検査(MWT)、客観的精神運動警戒タスク(objective psychomotor vigilance tasks)(PVT)、睡眠機能転帰質問票(Functional Outcomes of Sleep Questionnaire)(FOSQ)、多角的疲労評価尺度(Multidimensional Fatigue Inventory)(MFI)、重症度の臨床的全般印象度(Clinical Global Impression of Severity)(CGI−S)、改善度の臨床的全般印象度(Clinical Global Impression of Change)(CGI−C)、ベックうつ病質問票(Beck Depression Inventory)(BDI−II)、自己報告性の頭が朦朧とすることのスコア(self-reported fogginess scores)、自己報告性憂鬱スコア(self-reported mood scores)、または自己報告性眠気スコア(self-reported sleepiness scores)、に基づいて評価される、請求項1の薬学的組成物。
- 特発性過眠症を有する上記対象は、上記ESSについて少なくとも約3点、MWTにおける入眠潜時(SOL)に対して少なくとも約2分間、上記FOSQについて少なくとも約8点、一つ以上のMFI尺度について少なくとも約4点、CGI−SもしくはCGI−Cについて少なくとも1点、上記BDI−IIについて少なくとも約4点、または、自己報告性の頭が朦朧とすることのスコアについて、少なくとも約1.0点、の差で改善する、請求項1の薬学的組成物。
- PTZは、毎日二度、100mgの投与量で、少なくとも一週間の期間、投与される、請求項1の薬学的組成物。
- 特発性過眠症を有する対象の、頭が朦朧とすること(fogginess)を治療するための、ペンチレンテトラゾール(PTZ)を含む薬学的組成物。
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