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1.发明授权Nitrosated and nitrosylated prostaglandins, compositions and methods of use 失效亚硝化和亚硝酰化前列腺素，组合物和使用方法公开(公告)号：US07449595B2
公开(公告)日：2008-11-11
申请号：US11641050
申请日：2006-12-19
申请人： David S. Garvey , Ricky D. Gaston , L. Gordon Letts , Inigo Saenz de Tejada , Sang William Tam , Manuel Worcel
发明人： David S. Garvey , Ricky D. Gaston , L. Gordon Letts , Inigo Saenz de Tejada , Sang William Tam , Manuel Worcel
IPC分类号： C07C405/00 , A61K31/557
CPC分类号： A61K31/5575
摘要： The invention describes novel nitrosated and/or nitrosylated prostaglandins, and novel compositions comprising at least one nitrosated and/or nitrosylated prostaglandin, 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 invention also provides novel compositions comprising at least one prostaglandin and at least one S-nitrosothiol compound, and, optionally, at least one vasoactive agent. The prostaglandin is preferably a prostaglandin E1 compound, more preferably alprostadil, and the S-nitrosothiol compound is preferably S-nitrosoglutathione. The 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 cerebrovascular disorders, cardiovascular disorders, benign prostatic hyperplasia (BPH), glaucoma, peptic ulcers or for inducing abortions.
摘要翻译： 本发明描述了新的亚硝化和/或亚硝基化的前列腺素，以及包含至少一种亚硝化和/或亚硝基化的前列腺素的新组合物，以及任选的至少一种捐赠，转移或释放一氧化氮的化合物，提高内源性内皮水平的放松 因子，刺激一氧化氮的内源性合成或是一氧化氮合酶的底物和/或至少一种血管活性剂。 本发明还提供了包含至少一种前列腺素和至少一种S-亚硝基硫醇化合物和任选的至少一种血管活性剂的新型组合物。 前列腺素优选为前列腺素E 1化合物，更优选前列地尔，S-亚硝基硫醇化合物优选为S-亚硝基谷胱甘肽。 本发明还提供用于治疗或预防男性和女性的性功能障碍的方法，用于增强男性和女性的性反应，以及用于治疗或预防脑血管疾病，心血管疾病，良性前列腺增生（BPH），青光眼，消化性溃疡或诱导 堕胎
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2.发明授权Nitrostated and nitrosylated prostaglandins, compositions and methods of use 失效硝基化和亚硝酰化前列腺素，组合物和使用方法公开(公告)号：US07176238B1
公开(公告)日：2007-02-13
申请号：US09516194
申请日：2000-03-01
申请人： David S. Garvey , Ricky D. Gaston , L. Gordon Letts , Inigo Saenz de Tejada , Sang William Tam , Manuel Worcel
发明人： David S. Garvey , Ricky D. Gaston , L. Gordon Letts , Inigo Saenz de Tejada , Sang William Tam , Manuel Worcel
IPC分类号： A61K31/557 , C07C405/00
CPC分类号： A61K31/5575
摘要： The present invention describes novel nitrosated and/or nitrosylated prostaglandins, and novel compositions comprising at least one nitrosated and/or nitrosylated prostaglandin, 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 prostaglandin and at least one S-nitrosothiol compound, and, optionally, at least one vasoactive agent. The prostaglandin is preferably a prostaglandin E1 compound, more preferably alprostadil, and the S-nitrosothiol compound is preferably S-nitrosoglutathione. 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 cerebrovascular disorders, cardiovascular disorders, benign prostatic hyperplasia (BPH), glaucoma, peptic ulcers or for inducing abortions. The compounds and/or compositions of the present invention can also be provided in the form of a pharmaceutical kit.
摘要翻译： 本发明描述了新的亚硝基化和/或亚硝基化的前列腺素，以及包含至少一种亚硝基化和/或亚硝基化的前列腺素的新组合物，以及任选的至少一种捐赠，转移或释放一氧化氮的化合物，提高内源性的内皮水平 舒张因子，刺激一氧化氮的内源性合成或者是一氧化氮合酶的底物和/或至少一种血管活性剂。 本发明还提供了包含至少一种前列腺素和至少一种S-亚硝基硫醇化合物和任选的至少一种血管活性剂的新型组合物。 前列腺素优选为前列腺素E 1化合物，更优选前列地尔，S-亚硝基硫醇化合物优选为S-亚硝基谷胱甘肽。 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，以及用于治疗或预防脑血管疾病，心血管疾病，良性前列腺增生（BPH），青光眼，消化性溃疡或 诱导堕胎。 本发明的化合物和/或组合物也可以以药物试剂盒的形式提供。
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3.发明授权Nitrosated and nitrosylated prostaglandins, compositions and methods of use 失效亚硝化和亚硝酰化前列腺素，组合物和使用方法公开(公告)号：US07772278B2
公开(公告)日：2010-08-10
申请号：US12237117
申请日：2008-09-24
申请人： David S. Garvey , Ricky D. Gaston , L. Gordon Letts , Inigo Saenz de Tejada , Sang William Tam , Manuel Worcel
发明人： David S. Garvey , Ricky D. Gaston , L. Gordon Letts , Inigo Saenz de Tejada , Sang William Tam , Manuel Worcel
IPC分类号： A61K31/557 , C07C405/00
CPC分类号： A61K31/5575
摘要： The invention describes novel nitrosated and/or nitrosylated prostaglandins, and novel compositions comprising at least one nitrosated and/or nitrosylated prostaglandin, 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 invention also provides novel compositions comprising at least one prostaglandin and at least one S-nitrosothiol compound, and, optionally, at least one vasoactive agent. The prostaglandin is preferably a prostaglandin E1 compound, more preferably alprostadil, and the S-nitrosothiol compound is preferably S-nitrosoglutathione. The 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 cerebrovascular disorders, cardiovascular disorders, benign prostatic hyperplasia (BPH), glaucoma, peptic ulcers or for inducing abortions.
摘要翻译： 本发明描述了新的亚硝化和/或亚硝基化的前列腺素，以及包含至少一种亚硝化和/或亚硝基化的前列腺素的新组合物，以及任选的至少一种捐赠，转移或释放一氧化氮的化合物，提高内源性内皮水平的放松 因子，刺激一氧化氮的内源性合成或是一氧化氮合酶的底物和/或至少一种血管活性剂。 本发明还提供了包含至少一种前列腺素和至少一种S-亚硝基硫醇化合物和任选的至少一种血管活性剂的新型组合物。 前列腺素优选为前列腺素E1化合物，更优选前列地尔，S-亚硝基硫醇化合物优选为S-亚硝基谷胱甘肽。 本发明还提供用于治疗或预防男性和女性的性功能障碍的方法，用于增强男性和女性的性反应，以及用于治疗或预防脑血管疾病，心血管疾病，良性前列腺增生（BPH），青光眼，消化性溃疡或诱导 堕胎
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4.发明申请公开(公告)号：US20090088366A1
公开(公告)日：2009-04-02
申请号：US12237117
申请日：2008-09-24
IPC分类号： A61K38/02 , A61K31/215 , A61K31/4164 , A61K31/4375 , A61P15/00 , A61K31/496 , A61K31/7076
CPC分类号： A61K31/5575
摘要： The invention describes novel nitrosated and/or nitrosylated prostaglandins, and novel compositions comprising at least one nitrosated and/or nitrosylated prostaglandin, 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 invention also provides novel compositions comprising at least one prostaglandin and at least one S-nitrosothiol compound, and, optionally, at least one vasoactive agent. The prostaglandin is preferably a prostaglandin E1 compound, more preferably alprostadil, and the S-nitrosothiol compound is preferably S-nitrosoglutathione. The 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 cerebrovascular disorders, cardiovascular disorders, benign prostatic hyperplasia (BPH), glaucoma, peptic ulcers or for inducing abortions.
摘要翻译： 本发明描述了新的亚硝化和/或亚硝基化的前列腺素，以及包含至少一种亚硝化和/或亚硝基化的前列腺素的新组合物，以及任选的至少一种捐赠，转移或释放一氧化氮的化合物，提高内源性内皮水平的放松 因子，刺激一氧化氮的内源性合成或是一氧化氮合酶的底物和/或至少一种血管活性剂。 本发明还提供了包含至少一种前列腺素和至少一种S-亚硝基硫醇化合物和任选的至少一种血管活性剂的新型组合物。 前列腺素优选为前列腺素E1化合物，更优选前列地尔，S-亚硝基硫醇化合物优选为S-亚硝基谷胱甘肽。 本发明还提供用于治疗或预防男性和女性的性功能障碍的方法，用于增强男性和女性的性反应，以及用于治疗或预防脑血管疾病，心血管疾病，良性前列腺增生（BPH），青光眼，消化性溃疡或诱导 堕胎
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5.发明授权公开(公告)号：US06331543B1
公开(公告)日：2001-12-18
申请号：US09387727
申请日：1999-09-01
IPC分类号： A61K314985
CPC分类号： A61K31/195 , A61K31/075 , A61K31/21 , A61K31/34 , A61K31/40 , A61K31/44 , A61K31/47 , A61K31/4709 , A61K31/497 , A61K31/50 , A61K31/501 , A61K31/519 , A61K45/06 , C07D405/14 , C07D487/04
摘要： The present invention describes novel nitrosated and/or nitrosylated phosphodiesterase inhibitors, and novel compositions containing at least one nitrosated and/or nitrosylated phosphodiesterase inhibitor, and, optionally, one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or one or more vasoactive agents. The present invention also provides novel compositions containing at least one phosphodiesterase inhibitor, and one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or one or more vasoactive agents. 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 diseases induced by the increased metabolism of cyclic guanosine 3′,5′-monophosphate (cGMP), such as hypertension, pulmonary hypertension, congestive heart failure, renal failure, myocardial infraction, stable, unstable and variant (Prinzmetal) angina, atherosclerosis, cardiac edema, renal insufficiency, nephrotic edema, hepatic edema, stroke, asthma, bronchitis, chronic obstructive pulmonary disease (COPD), cystic fibrosis, dementia, immunodeficiency, premature labor, dysmenorrhoea, benign prostatic hyperplasis (BPH), bladder outlet obstruction, incontinence, conditions of reduced blood vessel patency, e.g., postpercutaneous transluminal coronary angioplasty (post-PTCA), peripheral vascular disease, allergic rhinitis, glucoma, and diseases characterized by disorders of gut motility, e.g., irritable bowel syndrome (IBS).
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6.发明授权Nitrosated and nitrosylated phosphodiesterase inhibitor compounds, compositions and their uses 失效亚硝化和亚硝基化磷酸二酯酶抑制剂化合物，组合物及其用途公开(公告)号：US06221881B1
公开(公告)日：2001-04-24
申请号：US09247292
申请日：1999-02-10
IPC分类号： C07D215227
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.
摘要翻译： 公开了具有式NOn-PDE抑制剂的亚硝基化和/或亚硝基化磷酸二酯酶抑制剂，其中n为1或2.本发明还提供了包含在药学上可接受的载体中的这些化合物的组合物。 本发明还提供了一种组合物，其包含治疗有效量的磷酸二酯酶抑制剂（PDE抑制剂），其可以任选地被至少一个NO或NO 2部分取代，以及一至十倍摩尔过量的捐赠，转移或释放的化合物 一氧化氮作为带电物质， 例如，亚硝酸盐（NO +）或硝酰基（NO-），或作为中性物质，一氧化氮（NO））或刺激内源性EDRF产生。 本发明还提供在药学上可接受的载体中包含这些化合物的组合物。 本发明还提供了治疗男性和女性性功能障碍的方法。
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7.发明授权Nitrosated and nitrosylated potassium channel activators, compositions and methods of use 失效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
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。
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8.发明授权Imidazoline &agr;-adrenergic receptor antagonist compounds in combination with nitric oxide donors, compositions and methods of use 失效咪唑啉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
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。
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9.发明授权Compositions and kits comprising alpha-adrenergic receptor antagonists and nitric oxide donors and methods of use 失效包含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
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。。
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10.发明授权公开(公告)号：US06172068B2
公开(公告)日：2001-01-09
申请号：US09247322
申请日：1999-02-10
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.
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