JP2009029828A - Rhoキナーゼ阻害剤とβ遮断薬からなる緑内障治療剤 - Google Patents
Rhoキナーゼ阻害剤とβ遮断薬からなる緑内障治療剤 Download PDFInfo
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- JP2009029828A JP2009029828A JP2008245694A JP2008245694A JP2009029828A JP 2009029828 A JP2009029828 A JP 2009029828A JP 2008245694 A JP2008245694 A JP 2008245694A JP 2008245694 A JP2008245694 A JP 2008245694A JP 2009029828 A JP2009029828 A JP 2009029828A
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- blocker
- kinase inhibitor
- rho kinase
- glaucoma
- therapeutic agent
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Abstract
【解決手段】Rhoキナーゼ阻害剤とβ遮断薬との組み合わせからなる緑内障治療剤であって、
該Rhoキナーゼ阻害剤が(R)−(+)−N−(1H−ピロロ[2,3−b]ピリジン−4−イル)−4−(1−アミノエチル)ベンズアミドであり、該β遮断薬がチモロール、ベフノロール、カルテオロール、ニプラジロール、ベタキソール、レボブノロールまたはメチプラノールである、緑内障治療剤である。
【選択図】図1
Description
本発明におけるRhoキナーゼ阻害剤((R)−(+)−N−(1H−ピロロ[2,3−b]ピリジン−4−イル)−4−(1−アミノエチル)ベンズアミド二塩酸塩)とβ遮断薬(チモロール)とを配合した点眼剤の一般的な製剤例を以下に示す。
(R)−(+)−N−(1H−ピロロ[2,3−b]ピリジン−4−イル)−4−(1−
アミノエチル)ベンズアミド二塩酸塩 0.1g
マレイン酸チモロール 0.34g
ホウ酸 0.2g
濃グリセリン 0.25g
塩化ベンザルコニウム 0.005g
希塩酸 適量
水酸化ナトリウム 適量
精製水 適量
上記処方において、Rhoキナーゼ阻害剤ならびにβ遮断薬の種類および量を変えて、また、添加剤の量を適宜変化させることで、所望の組合わせおよび所望の濃度の点眼剤を調整することができる。
Rhoキナーゼ阻害剤とβ遮断薬との組み合わせによる有用性を調べるため、実験動物にRhoキナーゼ阻害剤とβ遮断薬を併用投与した時の眼圧下降効果を検討した。Rhoキナーゼ阻害剤としては(R)−(+)−N−(1H−ピロロ[2,3−b]ピリジン−4−イル)−4−(1−アミノエチル)ベンズアミド二塩酸塩[化合物A]を、β遮断薬としてチモロールを使用した。
1.Rhoキナーゼ阻害剤溶液の調製
Rhoキナーゼ阻害剤を生理食塩水に溶解した後、水酸化ナトリウムを加えて溶液を中和し(pH6.0〜7.0)とし、所望の濃度のRhoキナーゼ阻害剤溶液を調製した。
市販のβ遮断薬点眼液をそのまま、または、生理食塩水で希釈して、所望の濃度のβ遮断薬溶液を調製した。
Rhoキナーゼ阻害剤とβ遮断薬とを併用投与した時の眼圧下降効果を検討した。比較対照として、Rhoキナーゼ阻害剤を単独投与またはβ遮断薬を単独投与した時の眼圧下降効果についても検討した。コントロールには基剤(生理食塩水)のみを投与した。
Rhoキナーゼ阻害剤溶液:0.1%化合物A溶液(点眼量:50μl)
β遮断薬溶液:チモロール点眼液(商品名:チモプトール0.25%、点眼量:50μl)
実験動物:日本白色ウサギ(系統:JW、性別:雄性、一群4匹)
(投与方法および測定方法)
1.Rhoキナーゼ阻害剤とβ遮断薬との併用投与
1) 4%塩酸オキシブプロカイン点眼液(商品名:ベノキシール0.4
%液)を実験動物の両眼に一滴点眼し局所麻酔をした。
β遮断薬溶液を生理食塩水に代え、他は上記併用投与試験と同じ方法で試験をした。
Rhoキナーゼ阻害剤溶液を生理食塩水に代え、他は上記併用投与試験と同じ方法で試験をした。
Rhoキナーゼ阻害剤溶液およびβ遮断薬溶液を生理食塩水に代え、他は上記併用投与試験と同じ方法で試験をした。
試験の結果を図1に示す。眼圧は初期眼圧からの変化値を示す。
Claims (2)
- Rhoキナーゼ阻害剤とβ遮断薬との組み合わせからなる緑内障治療剤であって、
該Rhoキナーゼ阻害剤が(R)−(+)−N−(1H−ピロロ[2,3−b]ピリジン−4−イル)−4−(1−アミノエチル)ベンズアミドであり、
該β遮断薬がチモロール、ベフノロール、カルテオロール、ニプラジロール、ベタキソール、レボブノロールまたはメチプラノール(Metipranolol)である、
緑内障治療剤。 - Rhoキナーゼ阻害剤とβ遮断薬との組み合わせからなり、お互いにその作用を補完および/または増強することを特徴とする緑内障治療剤であって、
該Rhoキナーゼ阻害剤が(R)−(+)−N−(1H−ピロロ[2,3−b]ピリジン−4−イル)−4−(1−アミノエチル)ベンズアミドであり、
該β遮断薬がチモロール、ベフノロール、カルテオロール、ニプラジロール、ベタキソール、レボブノロールまたはメチプラノール(Metipranolol)である、
緑内障治療剤。
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US11433090B2 (en) | 2017-06-16 | 2022-09-06 | The Doshisha | mTOR-inhibitor-containing medicine for treating or preventing ophthalmic symptoms, disorders, or diseases, and application thereof |
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ES2444841T3 (es) | 2014-02-27 |
CA2506464A1 (en) | 2004-06-03 |
EP1568382B1 (en) | 2013-11-06 |
KR101223886B1 (ko) | 2013-01-17 |
CA2506464C (en) | 2012-07-31 |
CN1323719C (zh) | 2007-07-04 |
EP1568382A1 (en) | 2005-08-31 |
JP2004182723A (ja) | 2004-07-02 |
KR20110045101A (ko) | 2011-05-03 |
JP4934653B2 (ja) | 2012-05-16 |
KR101103141B1 (ko) | 2012-01-04 |
EP1568382A4 (en) | 2007-08-01 |
US7972612B2 (en) | 2011-07-05 |
US20060052367A1 (en) | 2006-03-09 |
JP4314433B2 (ja) | 2009-08-19 |
CN1711107A (zh) | 2005-12-21 |
AU2003280812A1 (en) | 2004-06-15 |
WO2004045644A1 (ja) | 2004-06-03 |
US20110263638A1 (en) | 2011-10-27 |
KR20050075000A (ko) | 2005-07-19 |
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