JP2021518438A - 男性の避妊のための非ホルモン性組成物および方法 - Google Patents
男性の避妊のための非ホルモン性組成物および方法 Download PDFInfo
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Abstract
Description
α−1−アドレナリン受容体アンタゴニストと、
少なくとも1つの薬学的に許容される担体と
を含む徐放製剤であり、
前記避妊法が、毎日ほぼ同じ時間での前記組成物の1日1回の投与を含み、前記男性対象に持続的であり可逆性の無精液症、無精子症、または重篤な精子減少症をもたらし、
連続して少なくとも2日間の最初の期間の後、避妊が、その後の1日1回の摂取の遅延により損なわれない、
使用に関する。
1日1回の投与レジメンで投与した場合に、男性対象の避妊効果にとって十分である、無精液症、無精子症、または重篤な精子減少症の可逆的な状態を誘導するために有効な量のα−1−アドレナリン受容体アンタゴニストの徐放製剤と、
薬学的に許容される担体と
を含む組成物の1日1回の用量を投与するステップを含み、
連続した2日間の最初の期間の後に1日1回の投与を行うことができなくとも、男性対象の避妊効果にとって十分である、無精液症、無精子症、または重篤な精子減少症の持続的な状態に影響を与えない、
方法に関する。
1日1回の投与レジメンで投与される場合に、男性対象の避妊効果にとって十分である、無精液症、無精子症、または重篤な精子減少症の可逆的な状態を誘導するために有効な量のα−1−アドレナリン受容体アンタゴニストの徐放製剤と、
薬学的に許容される担体と
を含む組成物の1日1回の用量を投与するステップを含み、
連続した2日間の最初の期間の後に1日1回の投与を行うことができなくとも、男性対象の避妊効果にとって十分である、無精液症、無精子症、または重篤な精子減少症の持続的な状態に影響を与えない、
方法に関する。
1日1回の投与レジメンで投与される場合に、男性対象の避妊効果にとって十分である、無精液症、無精子症、または重篤な精子減少症の可逆的な状態を誘導するために有効な量のα−1−アドレナリン受容体アンタゴニストの徐放製剤と、
薬学的に許容される担体と
を含む組成物の1日1回の用量を男性対象に投与するステップを含み、
連続した2日間の最初の期間の後に1日1回の投与を行うことができなくとも、男性対象の避妊効果にとって十分である、無精液症、無精子症、または重篤な精子減少症の持続的な状態に影響を与えない、
方法に関する。
α−1−アドレナリン受容体アンタゴニストを含む組成物の使用
本発明は、男性対象のための非ホルモン性避妊法における組成物の使用であって、前記組成物が、α−1−アドレナリン受容体アンタゴニスト、好ましくはα−1a−アドレナリン受容体アンタゴニスト、より好ましくはシロドシンと、薬学的に許容される担体とを含む、使用に関する。非ホルモン性避妊法は、本発明に係る組成物の1日1回の投与を含む。男性対象に対し有効な曝露を維持するために、避妊法は、少なくとも2日間行われる。
一実施形態では、上述の本組成物の使用は、生物学的に有効な量のα−1−アドレナリン受容体アンタゴニストを含む。α−1−アドレナリン受容体アンタゴニストの生物学的に有効な量は、当業者の知識、α−1−アドレナリン受容体アンタゴニストの薬物動態のパラメータ、対象の年齢、健康状態などに基づき、当業者により決定され得る。
本発明の使用で投与される組成物の製剤の実施形態は、当該分野でよく知られている様々な剤形であり得るか、これらを含むか、またはこれらに類似し得る。たとえば、これは、カプセル剤、錠剤、カプレット剤、軟シェルカプセル剤、ゲルカプセル剤(ゲルカプセル)、液体組成物、散剤、濃縮粉末、液体と混合した濃縮粉末、咀嚼可能形態、嚥下可能形態、水溶性フィルム、顆粒形態、ペレットの形態、および経口液体懸濁剤を含み得る。
本発明は、いずれかのα−1−アドレナリン受容体アンタゴニストと共に実施され得る。当業者は、上記α−1−アドレナリン受容体アンタゴニストの薬力学的および薬物動態的な性質に関する一般的な知識を使用して、本組成物を適合させることができる。一実施形態では、α−1−アドレナリン受容体アンタゴニストは、シロドシン、テラゾシン、ドキサゾシン、タムスロシン、およびフィズキソシンを含む群から選択される。
i)約3時間〜約8時間の範囲のTmaxと、
ii)約70ng/mL未満の平均Cmaxと
を有するα−1−アドレナリン受容体アンタゴニストの薬物動態プロファイルを提供する。
i)約3時間〜約8時間の範囲のTmaxと、
ii)約50ng/mL未満の平均Cmaxと
を有するα−1−アドレナリン受容体アンタゴニストの薬物動態プロファイルを提供する。
本発明の一実施形態では、上述のα−1−アドレナリン受容体アンタゴニストは、上に記載されたいずれかの特定の形態の非ホルモン性避妊組成物に含まれ得るかまたは使用され得る。別の実施形態では、非ホルモン性避妊組成物は、上述のα−1−アドレナリン受容体アンタゴニストまたは当該分野で一般的に知られている範囲もしくは量の他の成分の組み合わせを含むかまたは使用し得る。
特定の実施形態では、様々な有効成分が、キットとして複数の組成物に組み込まれ得る。一部の実施形態では、本明細書中開示される非ホルモン性避妊組成物は、当業者に知られている物質を使用したキットとしてパッケージングされ得る。
本発明は、しかしながら、例えばカプセル剤、錠剤などの経口投与に限定されない。本発明の実施形態は、注射、経皮パッチ、または皮下インプラントなどの他の剤形または方法であり得るかこれを含み得る。これらもまた当該分野でよく知られており、本発明の実施形態において、たとえばそれぞれDepo−Provera(登録商標)、Ortho Evra(登録商標)、およびNexplanon(登録商標)などの比較可能な女性の避妊用製品と類似し得る。
一態様において、本発明は、男性の避妊のための方法に関する。この方法は、α−1−アドレナリン受容体アンタゴニストおよび薬学的に許容される担体を含む組成物の投与を含み、ここで本組成物は、男性対象に妊娠を行わせなくする無精液症、無精子症、または重篤な精子減少症を誘導することによる避妊効果を有する。
本発明において、以下の用語は以下の意味を有する。
この実施例は、(R)−シロドシンの徐放製剤に関する。
参照物質の即時放出(Urorec(登録商標))製剤および実施例1に係る実験上の徐放製剤Aからの(R)−シロドシンの溶解速度を比較するための溶解試験を、USP2型の装置の0.1NのHCl溶液900mlにおいて25℃、50rpmで行った。この比較した溶解速度の結果を、図1に提示する。
男性対象の処置における本発明の組成物の有効性を評価するための試験を行う。この試験の目的は、(R)−シロドシンの経口摂取が避妊効果をもたらすかどうかを決定することである。
(R)−シロドシン(SIL)の薬物動態の性質は、8mgの(R)−シロドシンを健常な志願者に単回投与した後に得られる血漿中濃度−対−時間プロファイルに基づき、モデル化される。(R)−シロドシンのデータは、一次速度定数と共に2コンパートメントモデルにより記載される。(R)−シロドシンの薬物動態の性質は、観察される血漿中濃度に基づき測定した。観察した血漿中濃度により、(R)−シロドシンの血漿中濃度のシミュレーション方法が有効であることが確認される。
このモデルは、8mgの(R)−シロドシンの少なくとも2回〜少なくとも5回の毎日の投与後の(R)−シロドシンの薬物動態の性質をシミュレートするために使用される。(R)−シロドシン製剤Aの投与の後、(R)−シロドシンの血漿中濃度は、図2に示されるように一定してC24を超えている。
製剤Aによる8および12mgの(R)−シロドシン徐放製剤の投与は、摂取が遅延する場合および1回飲み忘れる場合を含む、1日1回処置を通しての避妊の維持を可能にする。
Claims (15)
- 男性対象のための非ホルモン性避妊法における組成物の使用であって、前記組成物が、
α−1−アドレナリン受容体アンタゴニストと、
少なくとも1つの薬学的に許容される担体と
を含む徐放製剤であり、
前記避妊法が、毎日ほぼ同じ時間での前記組成物の1日1回の投与を含み、前記男性対象に持続的で可逆性の無精液症、無精子症、または重篤な精子減少症をもたらし、
連続して少なくとも2日間の最初の期間の後、避妊が、その後の1日1回の摂取が遅延しても損なわれない、
使用。 - 前記組成物が、経口投与される、請求項1に記載の使用。
- 連続した日数の最初の期間の後に、次回の用量の摂取が、最後の通常の毎日の投与時間から6〜18時間後まで遅延することができ、無精液症、無精子症、または重篤な精子減少症の状態が前記男性対象で維持される、請求項1または2に記載の使用。
- 連続した日数の最初の期間の後に、1日1回摂取できなくとも、無精液症、無精子症、または重篤な精子減少症の持続的な状態に影響を与えず、最後の摂取時間以後36〜48時間前記避妊法を維持する、請求項1〜3のいずれか1項に記載の使用。
- 前記避妊法が、少なくとも8日間行われる、請求項1〜4のいずれか1項に記載の使用。
- α−1−アドレナリン受容体アンタゴニストが、約0.1〜約30mg、好ましくは約0.2〜約20mgの範囲の量である、請求項1〜5のいずれか1項に記載の使用。
- α−1−アドレナリン受容体アンタゴニストが、(R)−シロドシンである、請求項1〜6のいずれか1項に記載の使用。
- (R)−シロドシンが、多形またはアモルファスの形態である、請求項1〜7のいずれか1項に記載の使用。
- 前記組成物が、徐放製剤で製剤化されている、請求項1〜8のいずれか1項に記載の使用。
- 前記組成物が、少なくとも1つの粒子、好ましくは少なくとも1つのコーティングされた粒子を含むかまたはからなり、平均粒径が、0.01〜5mm、好ましくは0.1〜2mmである、請求項1〜9のいずれか1項に記載の使用。
- 前記粒子が、カプセルに包有されており、各カプセルが、1日用量に達するために十分な数の粒子により充填されている、請求項1〜10のいずれか1項に記載の使用。
- 前記避妊が、前記男性対象による食物摂取とは無関係に達成される、請求項1〜11のいずれか1項に記載の使用。
- 毎日の投与の避妊法が、勃起不全の処置に適したさらなる組成物の同時投与または逐次投与をさらに含み;好ましくは前記さらなる組成物が、ホスホジエステラーゼ5阻害剤を含む、請求項1〜12のいずれか1項に記載の使用。
- それぞれの単位用量が1日用量である、請求項1〜12のいずれか1項に記載の組成物の少なくとも7、14、28、56、84、もしくは168〜365単位用量を含むか、または10、20、30、60、90、もしくは180〜360単位用量を含むパッケージング。
- 前記組成物が、約0.1〜約30mg、好ましくは約0.2〜約20mgの範囲の量のα−1−アドレナリン受容体アンタゴニストを含み、好ましくはα−1−アドレナリン受容体アンタゴニストが、8〜12mgの量の(R)−シロドシンである、請求項14に記載のパッケージング。
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