JP6178799B2 - アプレピタントl−プロリン溶媒和化合物−組成物及び共結晶 - Google Patents
アプレピタントl−プロリン溶媒和化合物−組成物及び共結晶 Download PDFInfo
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Description
本出願は、2011年11月25日に出願された米国出願第61/563,647号に対する優先権を請求し、その開示を参照により本明細書に組み込む。
サブスタンスP(ニューロキニン−1:NK−1)用の神経ペプチド受容体は、哺乳類の神経系、循環系及び末梢組織の至る所に分布しており、嗅覚、視覚、疼痛、血管拡張、胃運動性及び運動制御の知覚を含む幾つかの生物学的プロセスの調節に関与している。サブスタンスP拮抗薬は、神経精神疾患、炎症性疾患、疼痛(偏頭痛を含む)、皮膚疾患、喘息並びにその他の呼吸器疾患及び嘔吐に対するそれらの有用性に関して研究されている。サブスタンスPは、かゆみとしても一般的に知られた掻痒症の主要なメディエーターであることが知られている。研究は、サブスタンスP拮抗薬としてのアプレピタントが、掻痒症の処置における治療的効果を有し得ることが報告されてきた(S.Stander.「アプレピタントを用いたニューロキニン受容体1のターゲッティング:新規な止痒戦略(Targeting the neurokinin Receptor 1 with aprepitant:a novel antipruritic strategy)」PLoS One.2010年;5(6)e10968)。かゆみ又は皮膚刺激の種類としては、限定されるわけではないが、a)乾癬性掻痒症、血液透析によるかゆみ、水因性掻痒症、及び、皮膚障害(例えば、接触皮膚炎)、全身性障害、ニューロパチー、心因性の因子又はこれらの混合により起きるかゆみ、b)アレルギー反応、昆虫刺咬症、過敏症(例えば、乾皮症、座瘡、湿疹、乾癬)、炎症性状態又は怪我により起きるかゆみ、c)外陰部前庭炎に伴うかゆみ、並びに、d)例えば抗生物質、抗ウイルス剤及び抗ヒスタミン薬等の別の治療薬の投与からの皮膚刺激又は炎症性効果が挙げられる。
表1:GVS実験に関する方法パラメータ
試料は、等温線の完了後に回収し、XRPDにより再分析した。
1:1:1アプレピタントL−プロリンMeOH共結晶
1H NMRスペクトルにおける1.97ppmでのピークは、L−プロリンのピロリジン環上の2つのプロトンに対応する。このピークと、アプレピタントの芳香族プロトンの1つに対応する7.86ppmにおけるピークとの一体性の比較は、共結晶が1:1のアプレピタント:L−プロリン化学量論比を有することを示している。
1:1:1アプレピタントL−プロリンEtOH共結晶
1H NMRスペクトルにおける1.97ppmでのピークは、L−プロリンのピロリジン環上の2つのプロトンに対応する。このピークと、アプレピタントの芳香族プロトンの1つに対応する7.86ppmにおけるピークとの一体性の比較は、共結晶が1:1のアプレピタント:L−プロリン化学量論比を有することを示している。
1:1:1アプレピタントL−プロリンn−PrOH共結晶
Claims (13)
- 1:1:1アプレピタントL−プロリンメタノール組成物、1:1:1アプレピタントL−プロリンエタノール組成物、及び1:1:1アプレピタントL−プロリンn−プロパノール組成物から選択される、アプレピタントL−プロリン溶媒和化合物組成物。
- 1:1:1アプレピタントL−プロリンメタノール共結晶、1:1:1アプレピタントL−プロリンエタノール共結晶、及び1:1:1アプレピタントL−プロリンn−プロパノール共結晶から選択される、アプレピタントL−プロリン共結晶。
- 請求項1に記載のアプレピタントL−プロリン組成物又は請求項2に記載のアプレピタントL−プロリン共結晶及び薬学的に許容される担体を含む、医薬組成物。
- 嘔吐、神経精神疾患、炎症性疾患、疼痛、がん、皮膚疾患、かゆみ、呼吸器疾患、及び/又は中毒に関連する障害を処置する又は予防するための請求項3に記載の医薬組成物。
- 7.1、9.1、10.5、16.4、21.6及び21.9°2θ±0.2°2θにおけるピークから選択される少なくとも3つのピークを有する粉末X線回折パターン、
図1に示される粉末X線回折パターンに対応する粉末X線回折パターン、並びに
100KにおけるP212121空間群
の少なくとも1つを特徴とする、1:1:1アプレピタントL−プロリンメタノール共結晶。 - 請求項5に記載の1:1:1アプレピタントL−プロリンメタノール共結晶及び薬学的に許容される担体を含む、医薬組成物。
- 嘔吐、神経精神疾患、炎症性疾患、疼痛、がん、皮膚疾患、かゆみ、呼吸器疾患、及び/又は中毒に関連する障害を処置する又は予防するための請求項6に記載の医薬組成物。
- 7.2、9.1、10.4、16.2、21.6及び22.0°2θ±0.2°2θにおけるピークから選択される少なくとも3つのピークを有する粉末X線回折パターン、
図9に示される粉末X線回折パターンに対応する粉末X線回折パターン、並びに
100KにおけるP212121空間群
の少なくとも1つを特徴とする、1:1:1アプレピタントL−プロリンエタノール共結晶。 - 請求項8に記載の1:1:1アプレピタントL−プロリンエタノール共結晶及び薬学的に許容される担体を含む、医薬組成物。
- 嘔吐、神経精神疾患、炎症性疾患、疼痛、がん、皮膚疾患、かゆみ、呼吸器疾患、及び/又は中毒に関連する障害を処置する又は予防するための請求項9に記載の医薬組成物。
- 6.3、7.1、9.0、10.4、13.7及び17.3°2θ±0.2°2θにおけるピークから選択される少なくとも3つのピークを有する粉末X線回折パターン、
図14に示される粉末X線回折パターンに対応する粉末X線回折パターン、並びに
100KにおけるP212121空間群
の少なくとも1つを特徴とする、1:1:1アプレピタントL−プロリンn−プロパノール共結晶。 - 請求項11に記載の1:1:1アプレピタントL−プロリンn−プロパノール共結晶及び薬学的に許容される担体を含む、医薬組成物。
- 嘔吐、神経精神疾患、炎症性疾患、疼痛、がん、皮膚疾患、かゆみ、呼吸器疾患、及び/又は中毒に関連する障害を処置する又は予防するための請求項12に記載の医薬組成物。
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