JP2018080208A - トロスピウムの使用による膀胱排尿機能障害及び他の下部尿路疾患の治療のための薬物送達システム及び方法 - Google Patents
トロスピウムの使用による膀胱排尿機能障害及び他の下部尿路疾患の治療のための薬物送達システム及び方法 Download PDFInfo
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- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Abstract
Description
本出願は、2012年9月18日に出願された米国仮特許出願第61/702,576号に対する優先権を主張するものであり、参照によりその全体が本明細書に組み込まれる。
留置膀胱及び頸静脈カニューレを装着したラットに、塩化オキシブチニン、トルテロジンタータラート、又は塩化トロスピウムを膀胱内灌流する研究を実施した。手術後、ラットは完全に可動性があった。
酢酸と共に上昇する濃度の様々な投薬量の塩化オキシブチニン、トルテロジンタータラート、又は塩化トロスピウムで、頸動脈及び膀胱カテーテルを挿入したラットを膀胱内灌流した。対照期間及び治療期間の間、収縮間隔及び膀胱内圧を測定した。
囲を超える活動を示した。この観察に基づいて、適切なトロスピウムの膀胱内用量は、最
大180日間にわたって、約0.075mg/日〜約150mg/日の範囲であり得る。
150mgの高用量は、180日間続くことが一般的には意図されないが、より急性の適
用例に使用され得る。
生体外実験を行い、長期間にわたる塩化トロスピウムのゼロ次放出を示した。各デバイスに平均約77mgの塩化トロスピウムを装填した状態で、シリコーンチューブのデバイス筺体を使用した。シリコーンチューブ内径は1.5mmであった。グループ1(N=3)については、シリコーンチューブ壁は0.2mm厚であり、グループ2(N=3)については、シリコーンチューブ壁は0.8mmであった。各デバイスが、チューブの1つの端部に位置する放出用オリフィスを有する状態で、装填されたシリコーンチューブの端部を封鎖した。全デバイスのオリフィスの直径は、0.28mmであった。塩化トロスピウムは錠剤の形態であり、該錠剤の長さはおよそ3.8cmであり、該錠剤は、90%の塩化トロスピウム(TrosCl)、5%のPVP、及び5%のPEG8kから成る製剤を有した。
Claims (32)
- 膀胱組織内でトロスピウムの治療濃度を生じさせるために十分な、膀胱内の尿中トロスピウムの持続的な濃度を達成するために、患者の膀胱内に前記トロスピウムを局所的に投与することによる膀胱機能障害の治療に使用するための、トロスピウムを含む薬剤であって、
前記患者の膀胱内への前記局所的投与が、最大180日の治療期間にわたって、トロスピウム0.075mg/日〜約150mg/日の平均量においてである、薬剤。 - 前記患者の膀胱内への前記局所的投与が、トロスピウム0.15mg/日〜15mg/日の平均量においてである、請求項1に記載の薬剤。
- 前記治療期間が1日〜90日である、請求項1又は2に記載の薬剤。
- 前記治療期間が1日〜60日である、請求項1又は2に記載の薬剤。
- 前記患者の膀胱内への前記局所的投与が継続的である、請求項1に記載の薬剤。
- 前記患者の膀胱内への前記局所的投与が間欠的である、請求項1に記載の薬剤。
- 前記トロスピウムが、膀胱内の尿中にトロスピウムを放出する膀胱内薬物送達デバイスから膀胱内に送達される、請求項1に記載の薬剤。
- 前記膀胱内薬物送達デバイスが、前記治療期間にわたって、膀胱内の尿中にトロスピウムを継続的に放出する、請求項7に記載の薬剤。
- 前記膀胱内薬物送達デバイスが、トロスピウムを収容して制御可能に放出する筺体を備え、かつ前記デバイスを患者の膀胱内に保持するように構成される保持形状と、前記患者の尿道を通る前記デバイスの通過のための配置形状との間で弾性的に変形可能な筺体を備える、請求項7又は8に記載の薬剤。
- 前記筺体に収容される前記トロスピウムが非液体形態である、請求項9に記載の薬剤。
- 前記非液体形態が、錠剤、顆粒剤、半固体剤、カプセル剤、及びそれらの組み合わせから成る群から選択される、請求項10に記載の薬剤。
- トロスピウムが、膀胱に塗布されるコーティング物質から膀胱内に送達され、前記コーティング物質は、前記治療期間にわたって、膀胱内の尿中にトロスピウムを継続的に放出する、請求項1に記載の薬剤。
- 前記コーティング物質が粘膜付着性製剤を含む、請求項12に記載の薬剤。
- 前記局所的投与が、膀胱内に配置される尿道カテーテルを通じて、膀胱内に前記トロスピウムの液体形態をポンピングすることを含む、請求項1に記載の薬剤。
- 前記膀胱機能障害が、頻尿、切迫感、夜間多尿、排尿筋不安定に関連する切迫性尿失禁、切迫症候群、及び排尿筋反射亢進から成る群から選択される、請求項1に記載の薬剤。
- 前記トロスピウムが、塩化トロスピウム又はトロスピウムの別の薬学的に許容される塩の形態である、請求項1に記載の薬剤。
- 請求項1〜16のいずれか1項に記載の薬剤を含む薬物送達デバイスであって、前記薬物送達デバイスが膀胱内に挿入されるとトロスピウムを放出するように構成される、薬物送達デバイス。
- 膀胱機能障害の治療を必要とする患者にトロスピウムを投与する方法であって、
膀胱組織内でトロスピウムの治療濃度を生じさせるために十分な、膀胱内の尿中トロスピウムの持続的な濃度を達成するために、患者の膀胱内にトロスピウムを局所的に投与することを含む、方法。 - 前記患者の膀胱内への前記局所的投与が、最大180日の治療期間にわたって、トロスピウム0.075mg/日〜約150mg/日の平均量においてである、請求項18に記載の方法。
- 少なくとも第2の治療薬を前記患者に投与することをさらに含む、請求項18に記載の方法。
- 前記第2の治療薬が膀胱内に投与される、請求項20に記載の方法。
- 前記膀胱機能障害が、頻尿、切迫感、夜間多尿、排尿筋不安定に関連する切迫性尿失禁、切迫症候群、及び排尿筋反射亢進から成る群から選択される、請求項18に記載の方法。
- 前記トロスピウムが、塩化トロスピウム又はトロスピウムの別の薬学的に許容される塩の形態である、請求項18〜22のいずれか1項に記載の方法。
- 膀胱内挿入のために構成される筺体と、
トロスピウムの薬学的に許容される塩を含む投薬形態と、を備える、医療デバイスであって、
前記筺体が、前記投薬形態を保持し、膀胱機能障害の治療に対する治療有効量で、膀胱内に前記トロスピウムを放出するように構成される、医療デバイス。 - 最大180日の治療期間にわたって、0.075mg/日〜約150mg/日の平均量のトロスピウムを放出するように構成される、請求項24に記載のデバイス。
- 0.15mg/日〜15mg/日の平均量のトロスピウムを放出するように構成される、請求項25に記載のデバイス。
- 前記治療期間が1日〜90日である、請求項25又は26に記載のデバイス。
- 前記治療期間が1日〜60日である、請求項25又は26に記載のデバイス。
- 膀胱内挿入のために構成される筺体と、
トロスピウムを含む投薬形態と、を備える、医療デバイスであって、
前記筺体が、前記投薬形態を保持し、最大180日の治療期間にわたって、0.075mg/日〜約150mg/日の平均量のトロスピウムを放出するように構成される、医療デバイス。 - 0.15mg/日〜15mg/日の平均量のトロスピウムを放出するように構成される、請求項29に記載のデバイス。
- 前記治療期間が1日〜90日である、請求項29又は30に記載のデバイス。
- 前記治療期間が1日〜60日である、請求項29又は30に記載のデバイス。
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