JP2016502990A - ボルチオキセチンとドネペジルとを含む組成物 - Google Patents
ボルチオキセチンとドネペジルとを含む組成物 Download PDFInfo
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- JP2016502990A JP2016502990A JP2015547020A JP2015547020A JP2016502990A JP 2016502990 A JP2016502990 A JP 2016502990A JP 2015547020 A JP2015547020 A JP 2015547020A JP 2015547020 A JP2015547020 A JP 2015547020A JP 2016502990 A JP2016502990 A JP 2016502990A
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- vortioxetine
- dementia
- donepezil
- disease
- cognitive impairment
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Abstract
Description
これらの実験には成体雄性ウィスターラットを使用した。ラットは手術前に麻酔した。各動物を定位固定枠(Kopf Instruments、米国)に配置し、頭蓋頂部に切開を設けた。4mm2の曝露面を有する微小透析プローブ(ポリアクリルニトリル膜、Brainlink,オランダ)を腹側海馬に植え込んだ。座標はAP=−5.3mm(ブレグマまで)、外側+4.8mm(正中線まで)、腹側−8.0mm(脳硬膜まで)であり、切歯棒を−3.3mmに設定した[Paxinos and Watson,The rat brain in stereotaxic coordinates,Academic Press,6th edition,New York,2008]。プローブをステンレス鋼ネジ及び歯科用セメントで頭蓋に装着した。1日回復させた後に実験を開始した。
この実験は、本質的に実施例1に記載されるとおり行った。分析セットアップは以下のとおりいくらか変更した。クロマトグラフ分離は、4×2.0mmガードカラム(Phenomenex Synergy MAX−RP AJO−6073、Bester)で保護した逆相150×2.00mm(4μm)分析カラム(Phenomenex Synergy MAX−RP、Bester)で、いずれも温度を30℃に保ち実施した。移動相(均一濃度)は流量0.200ml/分の水、アセトニトリル(ACN)、及びトリフルオロ酢酸(TFA)(水:ACN:TFA=95.0:5:0.1v/v/v%)からなった。
これらの実験には成体雄性スプラーグドーリーラットを使用した。ラットは手術前に麻酔した。動物を定位固定枠(Kopf instruments、米国)に配置し、CMA12ガイドカニューレ(CMA Microdialysis、スウェーデン)を腹側海馬中に向けて植え込んだ。プローブ先端の座標は、AP=ブレグマまで−5.3mm、外側(ML)=正中線まで−4.8mm及び腹側=脳硬膜まで−8.0mmであった(Paxinos and Watson)。
実施例4は、試験化合物を除き本質的に実施例3と同様に行った。リバスチグミンは0.9%生理食塩水中に調製し、0.2mg/kg及び0.6mg/kgで皮下投与した。(S)−N−エチル−N−メチル−3[1−(ジメチルアミノ)エチル]−フェニルカルバメートを化学名とするリバスチグミンを、酒石酸塩として投与した。
新規物体認識課題(NOR)を使用して、単独又は併用でのボルチオキセチン及びドネペジルがスコポラミン誘発記憶障害を有するラットの記憶に及ぼす影響を評価した。スプラーグドーリーラットを使用した。
Claims (12)
- ボルチオキセチンとドネペジルとを薬学的に許容可能な賦形剤と共に含む医薬組成物。
- 5〜25mgのドネペジルを含む、請求項1に記載の組成物。
- 5〜20mgのボルチオキセチンを含む、請求項1又は2に記載の組成物。
- 認知機能障害;アルツハイマー病における認知症;血管性認知症;ピック病における認知症;クロイツフェルトヤコブ病における認知症;ハンチントン病における認知症;パーキンソン病における認知症;HIV(ヒト免疫不全ウイルス)における認知症;乱用者(アルコール又は薬物)における認知症;MCI(軽度認知障害);うつ病に付随する認知機能障害;及び統合失調症に付随する認知機能障害から選択される疾患の治療用薬剤を製造するためのボルチオキセチン及びドネペジルの使用。
- 前記薬剤が5〜25mgのドネペジルを含む、請求項4に記載の使用。
- 前記薬剤が5〜20mgのボルチオキセチンを含む、請求項4又は5に記載の使用。
- 認知機能障害;アルツハイマー病における認知症;血管性認知症;ピック病における認知症;クロイツフェルトヤコブ病における認知症;ハンチントン病における認知症;パーキンソン病における認知症;HIV(ヒト免疫不全ウイルス)における認知症;乱用者(アルコール又は薬物)における認知症;MCI(軽度認知障害);うつ病に付随する認知機能障害;及び統合失調症に付随する認知機能障害から選択される疾患の治療方法における使用のためのボルチオキセチン及びドネペジル。
- 前記ドネペジルが5〜25mgのドネペジルである、請求項7に記載の使用。
- 前記ボルチオキセチンが5〜20mgのボルチオキセチンである、請求項7又は8に記載の使用。
- 認知機能障害;アルツハイマー病における認知症;血管性認知症;ピック病における認知症;クロイツフェルトヤコブ病における認知症;ハンチントン病における認知症;パーキンソン病における認知症;HIV(ヒト免疫不全ウイルス)における認知症;乱用者(アルコール又は薬物)における認知症;MCI(軽度認知障害);うつ病に付随する認知機能障害;及び統合失調症に付随する認知機能障害から選択される疾患の治療方法であって、必要性のある患者に対するボルチオキセチンとドネペジルとの併用投与を含む方法。
- 前記患者に5〜25mgのドネペジルが投与される、請求項11に記載の使用。
- 前記患者に5〜20mgのボルチオキセチンが投与される、請求項10又は11に記載の使用。
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BR112018000841A8 (pt) * | 2015-07-17 | 2022-11-22 | Pasteur Institut | Agente estimulante de receptor 5-hidroxitriptamina1b para uso como um promotor de auto-renovação e/ou diferenciação de células satélites |
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