JP6441267B2 - 過活動膀胱を治療するためのβ−3アドレナリン受容体アゴニストおよびムスカリン受容体アンタゴニストの組み合わせ - Google Patents
過活動膀胱を治療するためのβ−3アドレナリン受容体アゴニストおよびムスカリン受容体アンタゴニストの組み合わせ Download PDFInfo
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Description
本出願は、2010年8月3日に出願された米国仮特許出願第61/370,171号の関連出願であり、米国特許法第119条(e)項に基づいて優先権の利益を主張し、その開示が全体として参照により本明細書に取り込まれる。
(i)治療有効量の化学式(I)の化合物、
(ii)治療有効量、または治療有効量以下の量の化学式(II)の化合物、
(i)治療有効量の化学式(I)の化合物、
(ii)治療有効量、または治療有効量以下の量の化学式(II)の化合物、
(i)治療有効量の化学式(I)の化合物、
(ii)治療有効量、または治療有効量以下の量の化学式(II)の化合物、
(i)治療有効量の化学式(I)の化合物、
(ii)治療有効量、または治療有効量以下の量の化学式(II)の化合物、
(i)治療有効量の化学式(I)の化合物、
(ii)治療有効量、または治療有効量以下の量の化学式(II)の化合物、
(i)治療有効量のβ−3アドレナリン受容体アゴニスト;
および
(ii)治療有効量、または治療有効量以下の量のムスカリン受容体アンタゴニスト、を投与することを含み、この際、(i)および(ii)両方の投与は、成分(i)および(ii)の個々での投与に比べて、相乗的に過活動膀胱(OAB)に関連する一連の症候を軽減するのに有効的である。
(i)治療有効量の化学式(I)のβ−3アドレナリン受容体アゴニスト、
および
(ii)治療有効量、または治療有効量以下の量の化学式(II)のムスカリン受容体アンタゴニスト、
BID 1日2回
ECG 心電図
g(グラム) mg(ミリグラム)
IR 即時放出(immediate release)
L(リットル) mL(ミリリットル)
μL(マイクロリットル) mol(モル)
M(モル濃度、モーラー) mM(ミリモーラー)
N(規定) Kg(キログラム)
mmol(ミリモル) RT(室温)
min(分) h(時間)
QID 1日4回
XL 持続放出(extended release)
1.健康ヒト被検体における薬物間相互作用の試験
薬物間相互作用の試験が健康ヒトボランティアにおいて行われた。それは、ソラベグロンおよびオキシブチニンの単独でまたはそれらの組み合わせでの重複経口投与を用いて、排尿後の(post void residual、PVR)残量を測定することにより薬物動態および薬力学のパラメーターを評価した。PVRは、それぞれの薬剤の単独投与治療およびそれらの組み合わせの投与治療を行った被検体の定常状態下で測定された。
−ソラベグロンおよび以下に示すその一次活性代謝産物
−R−オキシブチニン、S−オキシブチニンおよび以下に示すR−デスエチルオキシブチに代謝産物およびS−デスエチルオキシブチニン代謝産物。
組成物Aは、表1に示す成分(a)〜(e)を適切な高剪断ミキサー/製粒機で、ブレンドすることおよび湿式顆粒化をすることによって製造された。成分(f)〜(h)はドライの顆粒に添加され、ブレンドされ、圧縮された。圧縮されたタブレットは、水性フィルム層で覆われた。
PVR量を測定するために膀胱超音波走査を、それぞれの試験期間における、第1日目(投与期間より前の一日)および第6日目(投与期間の第6日目)に行った。
オキシブチニンXLを単独で投与した被検体におけるPVR量は、ベースラインに対して20.2の平均増加を示した一方、ソラベグロンとオキシブチニンXLとの組み合わせを投与した被検体におけるPVR量は、ベースラインに対して50.8の平均増加を示した。これらのデータは表2に示される。
膀胱遠心性神経の刺激がアセチルコリン(ACh)の放出をもたらし、それによって、膀胱平滑筋において接合後部(post−junctional)ムスカリン(M3)受容体を刺激し、収縮およびその後の排尿をもたらす。M2受容体は、ヒトの膀胱平滑筋において機能的に発現しており、膀胱収縮性においても役割を果たしている可能性があるが、これはおそらく、間接的にM3媒介性の収縮を増強し、β−3アドレナリン受容体仲介の弛緩を抑制することによるものであろう。抗ムスカリン剤は、主にM3受容体を阻害する作用を示し、これにより過活動膀胱に関連する収縮を抑制するものと考えられている。
Claims (18)
- (i)治療有効量のβ−3アドレナリン受容体アゴニスト、および
(ii)治療有効量、または治療有効量以下の量のムスカリン受容体アンタゴニスト、を含み、前記個々の成分(i)および(ii)に比べて相乗的に過活動膀胱(OAB)に関連する一以上の症候を治療するための組み合わせ剤であって、
前記β−3アドレナリン受容体アゴニストは、ソラベグロン、またはその製薬上許容可能な塩、その製薬上許容可能な溶媒和物、もしくはその製薬上許容可能な溶媒で溶媒和した製薬上許容可能な塩を含み、
前記ムスカリン受容体アンタゴニストは、オキシブチニン、トルテロジン、およびソリフェナシン、またはその製薬上許容可能な塩、その製薬上許容可能な溶媒和物、もしくはその製薬上許容可能な溶媒で溶媒和した製薬上許容可能な塩からなる群から選択される、組み合わせ剤。 - 前記過活動膀胱に関連する一以上の症候は、切迫の頻尿(frequency of urgency)、夜間頻尿、および尿失禁からなる群より選択される、請求項1に記載の組み合わせ剤。
- 前記ムスカリン受容体アンタゴニストは、オキシブチニン、またはその製薬上許容可能な塩、その製薬上許容可能な溶媒和物、もしくはその製薬上許容可能な溶媒で溶媒和した製薬上許容可能な塩を含む、請求項1または2に記載の組み合わせ剤。
- 前記ソラベグロンの製薬上許容可能な塩は、塩酸塩を含む、請求項1〜3のいずれか1項に記載の組み合わせ剤。
- 請求項1〜4のいずれか1項に記載の組み合わせ剤に、一以上の製薬上許容可能なキャリア、希釈剤、または賦形剤をさらに含む、医薬組成物。
- 哺乳類における過活動膀胱に関連する一以上の症候を治療するために、治療有効量でそれを必要とする哺乳類に投与されるように用いられる、請求項5に記載の医薬組成物。
- 哺乳類における過活動膀胱に関連する一以上の症候を治療するために投与される、
(i)治療有効量のβ−3アドレナリン受容体アゴニスト、および
(ii)治療有効量、または治療有効量以下の量のムスカリン受容体アンタゴニスト、
を含み、
前記β−3アドレナリン受容体アゴニストは、ソラベグロン、またはその製薬上許容可能な塩、その製薬上許容可能な溶媒和物、もしくはその製薬上許容可能な溶媒で溶媒和した製薬上許容可能な塩を含み、
前記ムスカリン受容体アンタゴニストは、オキシブチニン、トルテロジン、およびソリフェナシン、またはその製薬上許容可能な塩、その製薬上許容可能な溶媒和物、もしくはその製薬上許容可能な溶媒で溶媒和した製薬上許容可能な塩からなる群から選択される、組み合わせ剤。 - 前記過活動膀胱に関連する一以上の症候は、切迫の頻尿、夜間頻尿、および尿失禁からなる群より選択される、請求項7に記載の組み合わせ剤。
- 前記ムスカリン受容体アンタゴニストは、オキシブチニン、またはその製薬上許容可能な塩、その製薬上許容可能な溶媒和物、もしくはその製薬上許容可能な溶媒で溶媒和した製薬上許容可能な塩を含む、請求項7または8に記載の組み合わせ剤。
- 成分(i)および(ii)を、同時投与する(co−administered)、請求項7〜9のいずれか1項に記載の組み合わせ剤。
- 成分(i)および(ii)を、単一の剤形に包含する、請求項7〜10のいずれか1項に記載の組み合わせ剤。
- 成分(i)および(ii)を、個別で投与する、請求項7〜10のいずれか1項に記載の組み合わせ剤。
- 成分(i)および(ii)の投与の間に、時間差がある、請求項7〜9および12のいずれか1項に記載の組み合わせ剤。
- 前記ソラベグロンの製薬上許容可能な塩は、塩酸塩を含む、請求項7〜13のいずれか1項に記載の組み合わせ剤。
- 請求項7〜14のいずれか1項に記載の組み合わせ剤に、一以上の製薬上許容可能なキャリア、希釈剤、または賦形剤をさらに含む、医薬組成物。
- 哺乳類における過活動膀胱に関連する一以上の症候を治療するために、治療有効量でそれを必要とする哺乳類に投与されるように用いられる、請求項15に記載の医薬組成物。
- 過活動膀胱に関連する一以上の症候を治療するための薬剤の調製における、
化学式(I)
ムスカリン受容体アンタゴニスト、との組み合わせの、使用であって、
前記ムスカリン受容体アンタゴニストは、オキシブチニン、トルテロジン、およびソリフェナシン、またはその製薬上許容可能な塩、その製薬上許容可能な溶媒和物、もしくはその製薬上許容可能な溶媒で溶媒和した製薬上許容可能な塩からなる群から選択される、使用。 - 哺乳類における過活動膀胱に関連する一以上の症候を治療するために投与される、
化学式(I)
ムスカリン受容体アンタゴニスト、との組み合わせ剤であって、
前記ムスカリン受容体アンタゴニストは、オキシブチニン、トルテロジン、およびソリフェナシン、またはその製薬上許容可能な塩、その製薬上許容可能な溶媒和物、もしくはその製薬上許容可能な溶媒で溶媒和した製薬上許容可能な塩からなる群から選択される、組み合わせ剤。
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CN103269692A (zh) | 2013-08-28 |
SG187689A1 (en) | 2013-03-28 |
NZ607485A (en) | 2015-04-24 |
AU2011285928B2 (en) | 2016-06-16 |
AR084122A1 (es) | 2013-04-24 |
CA2807135A1 (en) | 2012-02-09 |
WO2012018773A1 (en) | 2012-02-09 |
CL2013000342A1 (es) | 2013-06-28 |
CN103269692B (zh) | 2018-02-23 |
MX2013001342A (es) | 2013-03-22 |
US8642661B2 (en) | 2014-02-04 |
MX353105B (es) | 2017-12-19 |
US20120035118A1 (en) | 2012-02-09 |
CA2807135C (en) | 2019-05-14 |
CO6680685A2 (es) | 2013-05-31 |
AP2013006742A0 (en) | 2013-02-28 |
KR20130135239A (ko) | 2013-12-10 |
SG10201506076TA (en) | 2015-09-29 |
AU2011285928A1 (en) | 2013-03-07 |
PE20131341A1 (es) | 2013-12-07 |
EA030145B1 (ru) | 2018-06-29 |
EP2600859A1 (en) | 2013-06-12 |
JP2013535486A (ja) | 2013-09-12 |
EA201390066A1 (ru) | 2013-07-30 |
KR20180008918A (ko) | 2018-01-24 |
BR112013002511A2 (pt) | 2017-06-27 |
JP2017002074A (ja) | 2017-01-05 |
TW201208667A (en) | 2012-03-01 |
AU2011285928B9 (en) | 2018-08-02 |
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