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1. 发明授权

US06514934B1 Imidazoline &agr;-adrenergic receptor antagonist compounds in combination with nitric oxide donors, compositions and methods of use 失效
标题翻译：咪唑啉α-肾上腺素能受体拮抗剂化合物与一氧化氮供体的组合物和使用方法
公开(公告)号：US06514934B1
公开(公告)日：2003-02-04
申请号：US09280540
申请日：1999-03-30
申请人： David S. Garvey , Joseph D. Schroeder , Inigo Saenz de Tejada
发明人： David S. Garvey , Joseph D. Schroeder , Inigo Saenz de Tejada
IPC分类号： A61K3800
CPC分类号： C07D459/00 , A61K45/06 , C07C381/00 , C07D211/62 , C07D233/24 , C07D239/95 , C07D401/04 , C07D405/12 , Y10S514/929 , Y10S514/968
摘要： The present invention is directed to nitrosated or nitrosylated &agr;-adrenergic receptor antagonists, compositions comprising &agr;-adrenergic receptor antagonists that are optionally substituted with at least one NO or NO2 moiety and compounds that donate, transfer or release nitric oxide or elevate levels of endogenous endothelium-derived relaxing factor, and methods for treating sexual dysfunctions in males and females.
摘要翻译：本发明涉及亚硝基化或亚硝基化的α-肾上腺素能受体拮抗剂，其包含任选被至少一个NO或NO 2部分取代的α-肾上腺素能受体拮抗剂的组合物和捐赠，转移或释放一氧化氮或升高内源性内皮水平的化合物来源的放松因子，以及治疗男性和女性性功能障碍的方法。

2. 发明授权

US06294517B1 Compositions and kits comprising alpha-adrenergic receptor antagonists and nitric oxide donors and methods of use 失效
标题翻译：包含α-肾上腺素能受体拮抗剂和一氧化氮供体的组合物和试剂盒及使用方法
公开(公告)号：US06294517B1
公开(公告)日：2001-09-25
申请号：US09145143
申请日：1998-09-01
申请人： David S. Garvey , Joseph D. Schroeder , Inigo Saenz de Tejada
发明人： David S. Garvey , Joseph D. Schroeder , Inigo Saenz de Tejada
IPC分类号： A01N4354
CPC分类号： C07D459/00 , A61K45/06 , C07C381/00 , C07D211/62 , C07D233/24 , C07D239/95 , C07D401/04 , C07D405/12 , Y10S514/929 , Y10S514/968
摘要： The present invention describes novel compositions and kits comprising alpha-adrenergic receptor antagonists and compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, or stimulate nitric oxide synthesis. In preferred embodiments, the alpha-adrenergic receptor antagonist is an alkaloid selected from the group consisting of rauwolscine, corynanthine, yohimbine, apoyohimbine, beta-yohimbine, yohimbol, pseudoyohimbine and epi-3&agr;-yohimbine, and the compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, or stimulates nitric oxide synthesis is selected from the group consisting of L-arginine, S-nitroso-N-acetylcysteine, S-nitroso-captopril, S-nitroso-homocysteine, S-nitroso-cysteine and S-nitroso-glutathione. In other embodiments, the present invention describes novel compositions comprising yohimbine and L-arginine. In still other embodiments, the invention describes novel compositions comprising yohimbine and L-arginine where the yohimbine is derived from yohimbe bark or Rauwolfia root. The novel compositions of the invention are useful for treating impotence in males and females.
摘要翻译：本发明描述了包含α-肾上腺素能受体拮抗剂和捐赠，转移或释放一氧化氮，提高内源性松弛因子的内源水平或刺激一氧化氮合成的化合物的新型组合物和试剂盒。在优选的实施方案中，α-肾上腺素能受体拮抗剂是选自以下的生物碱：羊尿苷，色氨酸，育亨宾，去氨嘌呤，β-育亨宾，育亨宾，假蛋黄嘌呤和epi-3α-育亨宾，以及捐赠，转移或释放的化合物一氧化氮提高内源性舒张因子的内源水平，或刺激一氧化氮合成选自L-精氨酸，S-亚硝基-N-乙酰半胱氨酸，S-亚硝基卡托普利，S-亚硝基高半胱氨酸，S 亚硝基半胱氨酸和S-亚硝基 - 谷胱甘肽。在其它实施方案中，本发明描述了包含育亨宾和L-精氨酸的新型组合物。在其它实施方案中，本发明描述了包含育亨宾和L-精氨酸的新型组合物，其中育亨宾衍生自yohimbe树皮或Rauwolfia根。本发明的新型组合物可用于治疗男性和女性的阳。。

3. 发明授权

US06417162B1 Nitrosated and nitrosylated &agr;-adrenergic receptor antagonist compounds, compositions and their uses 失效
公开(公告)号：US06417162B1
公开(公告)日：2002-07-09
申请号：US09306809
申请日：1999-05-07
申请人： David S. Garvey , Joseph D. Schroeder , Inigo Saenz de Tejada
发明人： David S. Garvey , Joseph D. Schroeder , Inigo Saenz de Tejada
IPC分类号： A01N4354
CPC分类号： C07D459/00 , A61K45/06 , C07C381/00 , C07D211/62 , C07D233/24 , C07D239/95 , C07D401/04 , C07D405/12 , Y10S514/929 , Y10S514/968
摘要： The present invention is directed to nitrosated or nitrosylated &agr;-adrenergic receptor antagonists, compositions comprising &agr;-adrenergic receptor antagonists that are optionally substituted with at least one NO or NO2 moiety and compounds that donate, transfer or release nitric oxide or elevate levels of endogenous endothelium-derived relaxing factor, and methods for treating sexual dysfunctions in males and females.

4. 发明授权

US06433182B1 Nitrosated and nitrosylated &agr;-adrenergic receptor antagonist compounds, compositions and their uses 失效
标题翻译：亚硝化和亚硝酰化的α-肾上腺素能受体拮抗剂化合物，组合物及其用途
公开(公告)号：US06433182B1
公开(公告)日：2002-08-13
申请号：US09306805
申请日：1999-05-07
申请人： David S. Garvey , Joseph D. Schroeder , Inigo Saenz de Tejada
发明人： David S. Garvey , Joseph D. Schroeder , Inigo Saenz de Tejada
IPC分类号： C07D23500
CPC分类号： C07D459/00 , A61K45/06 , C07C381/00 , C07D211/62 , C07D233/24 , C07D239/95 , C07D401/04 , C07D405/12 , Y10S514/929 , Y10S514/968
摘要： The present invention is directed to nitrosated or nitrosylated &agr;-adrenergic receptor antagonists, compositions comprising &agr;-adrenergic receptor antagonists that are optionally substituted with at least one NO or NO2 moiety and compounds that donate, transfer or release nitric oxide or elevate levels of endogenous endothelium-derived relaxing factor, and methods for treating sexual dysfunctions in males and females.
摘要翻译：本发明涉及亚硝基化或亚硝基化的α-肾上腺素能受体拮抗剂，其包含任选被至少一个NO或NO 2部分取代的α-肾上腺素能受体拮抗剂的组合物和捐赠，转移或释放一氧化氮或升高内源性内皮水平的化合物来源的放松因子，以及治疗男性和女性性功能障碍的方法。

5. 发明授权

US5994294A Nitrosated and nitrosylated .alpha.-adrenergic receptor antagonist compounds, compositions and their uses 失效
标题翻译：亚硝化和亚硝酰化的α-肾上腺素能受体拮抗剂化合物，组合物及其用途
公开(公告)号：US5994294A
公开(公告)日：1999-11-30
申请号：US714313
申请日：1996-09-18
申请人： David S. Garvey , Joseph D. Schroeder , Inigo Saenz de Tejada
发明人： David S. Garvey , Joseph D. Schroeder , Inigo Saenz de Tejada
IPC分类号： C07D295/08 , A61K31/00 , A61K31/22 , A61K31/222 , A61K31/415 , A61K31/4164 , A61K31/4178 , A61K31/475 , A61K31/495 , A61K31/505 , A61K31/506 , A61K31/517 , A61K38/00 , A61P15/00 , A61P15/10 , C07C217/60 , C07C311/37 , C07C381/00 , C07D211/62 , C07D233/24 , C07D239/95 , C07D401/04 , C07D405/12 , C07D459/00 , C07D487/04 , C07K5/06 , C07K5/08
CPC分类号： C07D459/00 , C07C381/00 , C07D211/62 , C07D233/24 , C07D239/95 , C07D401/04 , C07D405/12 , Y10S514/929
摘要： Disclosed are nitrosated and nitrosylated .alpha.-adrenergic receptor antagonists, compositions of an .alpha.-adrenergic receptor antagonist (.alpha.-antagonist), which can optionally be substituted with at least one NO or NO.sub.2 moiety, and a compound that donates, transfers or releases nitric oxide as a charged species, i.e., nitrosonium (NO.sup.+) or nitroxyl (NO.sup.-), or as the neutral species, nitric oxide (NO.cndot.); and uses for each of them in treating human impotence or erectile dysfunction.
摘要翻译：公开了亚硝化和亚硝基化的α-肾上腺素能受体拮抗剂，可以任选被至少一个NO或NO 2部分取代的α-肾上腺素能受体拮抗剂（α-拮抗剂）的组合物，以及捐赠，转移或释放一氧化氮作为带电物种，即亚硝酸盐（NO +）或硝酰基（NO-），或作为中性物质，一氧化氮（NO）; 并用于每个人治疗人类阳ence或勃起功能障碍。

6. 发明授权

US06323211B1 Compositions and methods for treating sexual dysfunctions 失效
标题翻译：用于治疗性功能障碍的组合物和方法
公开(公告)号：US06323211B1
公开(公告)日：2001-11-27
申请号：US09285048
申请日：1999-04-02
申请人： David S. Garvey , Joseph D. Schroeder , Inigo Saenz de Tejada
发明人： David S. Garvey , Joseph D. Schroeder , Inigo Saenz de Tejada
IPC分类号： A61K3144
CPC分类号： A61K31/475 , A61K45/06 , C07C381/00 , C07D211/62 , C07D233/24 , C07D239/95 , C07D401/04 , C07D405/12 , C07D459/00 , Y10S514/929 , Y10S514/968 , A61K31/195 , A61K2300/00
摘要： The present invention describes methods for preventing and treating sexual dysfunctions in patients by orally administering at least one &agr;-adrenergic receptor antagonist and at least one compound that elevates endogenous nitric oxide or endothelium-derived relaxing factor in vivo. The present invention also describes orally administrable compositions comprising at least one &agr;-adrenergic receptor antagonist and at least one compound that elevates endogenous nitric oxide or endothelium-derived relaxing factor in vivo. In the present invention, the &agr;-adrenergic receptor antagonist is preferably yohimbine or phentolamine, and the compound that elevates endogenous nitric oxide or endothelium-derived relaxing factor in vivo is preferably L-arginine.
摘要翻译：本发明描述了通过口服施用至少一种α-肾上腺素能受体拮抗剂和至少一种在体内升高内源性一氧化氮或内皮衍生的松弛因子的化合物来预防和治疗患者的性功能障碍的方法。本发明还描述了包含至少一种α-肾上腺素能受体拮抗剂和至少一种在体内升高内源性一氧化氮或内皮衍生的松弛因子的化合物的可口服给药的组合物。在本发明中，α-肾上腺素能受体拮抗剂优选育亨宾或酚妥拉明，并且在体内升高内源性一氧化氮或内皮衍生的松弛因子的化合物优选为L-精氨酸。

7. 发明授权

US5932538A Nitrosated and nitrosylated .alpha.-adrenergic receptor antagonist compounds, compositions and their uses 失效
标题翻译：亚硝化和亚硝酰化的α-肾上腺素能受体拮抗剂化合物，组合物及其用途
公开(公告)号：US5932538A
公开(公告)日：1999-08-03
申请号：US595732
申请日：1996-02-02
申请人： David S. Garvey , Joseph D. Schroeder , Inigo Saenz de Tejada
发明人： David S. Garvey , Joseph D. Schroeder , Inigo Saenz de Tejada
IPC分类号： C07D295/08 , A61K31/00 , A61K31/22 , A61K31/222 , A61K31/415 , A61K31/4164 , A61K31/4178 , A61K31/475 , A61K31/495 , A61K31/505 , A61K31/506 , A61K31/517 , A61K38/00 , A61P15/00 , A61P15/10 , C07C217/60 , C07C311/37 , C07C381/00 , C07D211/62 , C07D233/24 , C07D239/95 , C07D401/04 , C07D405/12 , C07D459/00 , C07D487/04 , A01N43/54 , A61K31/13
CPC分类号： C07D459/00 , C07C381/00 , C07D211/62 , C07D233/24 , C07D239/95 , C07D401/04 , C07D405/12
摘要： Disclosed are nitrosated and nitrosylated .alpha.-adrenergic receptor antagonists, compositions of an .alpha.-adrenergic receptor antagonist (.alpha.-antagonist), which can optionally be substituted with at least one NO or NO.sub.2 moiety, and a compound that donates, transfers or releases nitric oxide as a charged species, i.e., nitrosonium (NO.sup.+) or nitroxyl (NO.sup.-), or as the neutral species, nitric oxide (NO.circle-solid.); and uses for each of them in treating human male impotence or erectile dysfunction.
摘要翻译：公开了亚硝化和亚硝基化的α-肾上腺素能受体拮抗剂，可以任选被至少一个NO或NO 2部分取代的α-肾上腺素能受体拮抗剂（α-拮抗剂）的组合物，以及捐赠，转移或释放一氧化氮作为带电物种，即亚硝酸盐（NO +）或硝酰基（NO-），或作为中性物质，一氧化氮（NO + 574）; 并用于每个人治疗人类男性阳ence或勃起功能障碍。

8. 发明授权

US06693122B2 Nitrosated and nitrosylated potassium channel activators, compositions and methods of use 失效
标题翻译：亚硝化和亚硝基化钾通道激活剂，组合物和使用方法
公开(公告)号：US06693122B2
公开(公告)日：2004-02-17
申请号：US10154916
申请日：2002-05-28
申请人： David S. Garvey , Inigo Saenz de Tejada
发明人： David S. Garvey , Inigo Saenz de Tejada
IPC分类号： A61K3144
CPC分类号： C07D213/82 , A61K31/4406 , A61K31/455
摘要： The present invention describes novel nitrosated and/or nitrosylated potassium channel activators, and novel compositions comprising at least one nitrosated and/or nitrosylated potassium channel activator, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one vasoactive agent. The present invention also provides novel compositions comprising at least one potassium channel activator, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one vasoactive agent. The present invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses in males and females, and for treating or preventing cardiovascular disorders, cerebrovascular disorders, hypertension, asthma, baldness, urinary incontinence, epilepsy, sleep disorders, gastrointestinal disorders, migraines, irritable bowel syndrome and sensitive skin.
摘要翻译：本发明描述了新的亚硝化和/或亚硝基化的钾通道激活剂，以及包含至少一种亚硝化和/或亚硝基化钾通道活化剂的新组合物，以及任选的至少一种捐赠，转移或释放一氧化氮的化合物，提高内源性水平的内皮衍生的松弛因子，刺激一氧化氮的内源性合成或者是一氧化氮合酶和/或至少一种血管活性剂的底物。本发明还提供了包含至少一种钾通道活化剂和至少一种捐赠，转移或释放一氧化氮的化合物的新型组合物，提高内源性内皮衍生的舒张因子水平，刺激一氧化氮的内源性合成，或者是用于一氧化氮合酶和/或至少一种血管活性剂。本发明还提供了治疗或预防男性和女性性功能障碍的方法，用于增强男性和女性的性反应，以及治疗或预防心血管疾病，脑血管障碍，高血压，哮喘，秃发，尿失禁，癫痫，睡眠障碍胃肠道疾病，偏头痛，肠易激综合征和敏感性皮肤。

9. 发明授权

US06172068B2 Nitrosated and nitrosylated phosphodiesterase inhibitor compounds, compositions and their uses 失效
公开(公告)号：US06172068B2
公开(公告)日：2001-01-09
申请号：US09247322
申请日：1999-02-10
申请人： David S. Garvey , Inigo Saenz de Tejada
发明人： David S. Garvey , Inigo Saenz de Tejada
IPC分类号： C07D40104
CPC分类号： C07D487/04 , C07D405/14
摘要： Disclosed are nitrosated and/or nitrosylated phosphodiesterase inhibitors having the formula NOn-PDE inhibitor where n is 1 or 2. The invention also provides compositions comprising such compounds in a pharmaceutically acceptable carrier. The invention also provides a composition comprising a therapeutically effective amount of an phosphodiesterase inhibitor (PDE inhibitor), which can optionally be substituted with at least one NO or NO2 moiety, and one to ten fold molar excess of a compound that donates, transfers or releases nitrogen monoxide as a charged species, i. e., nitrosonium (NO+) or nitroxyl (NO−), or as the neutral species, nitric oxide (NO•) or which stimulates endogenous EDRF production. The invention also provides compositions comprising such compounds in a pharmaceutically acceptable carrier. The invention also provides methods for treating sexual dysfunctions in males and females.

10. 发明授权

US06172060B2 Nitrosated and nitrosylated phosphodiesterase inhibitor compounds, compositions and their uses 失效
公开(公告)号：US06172060B2
公开(公告)日：2001-01-09
申请号：US09247296
申请日：1999-02-10
申请人： David S. Garvey , Inigo Saenz de Tejada
发明人： David S. Garvey , Inigo Saenz de Tejada
IPC分类号： C07D20712
CPC分类号： C07D487/04 , C07D405/14
摘要： Disclosed are nitrosated and/or nitrosylated phosphodiesterase inhibitors having the formula NOn-PDE inhibitor where n is 1 or 2. The invention also provides compositions comprising such compounds in a pharmaceutically acceptable carrier. The invention also provides a composition comprising a therapeutically effective amount of an phosphodiesterase inhibitor (PDE inhibitor), which can optionally be substituted with at least one NO or NO2 moiety, and one to ten fold molar excess of a compound that donates, transfers or releases nitrogen monoxide as a charged species, i.e., nitrosonium (NO+) or nitroxyl (NO−), or as the neutral species, nitric oxide (NO•) or which stimulates endogenous EDRF production. The invention also provides compositions comprising such compounds in a pharmaceutically acceptable carrier. The invention also provides methods for treating sexual dysfunctions in males and females.

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