公开(公告)号：US20060063774A1

公开(公告)日：2006-03-23

申请号：US10943982

申请日：2004-09-20

申请人： David Garvey ,  Inigo Tejada

发明人： David Garvey ,  Inigo Tejada

IPC分类号： A61K31/54 ,  A61K31/519 ,  A61K31/50 ,  A61K31/44 ,  A61K31/4015

CPC分类号： A61K31/4015 ,  A61K31/44 ,  A61K31/50 ,  A61K31/519 ,  A61K31/54

摘要： The invention provides phosphodiesterase inhibitors and/or nitric oxide donors that are useful in treating male impotence, female sexual dysfunction and anal diseases.

摘要翻译： 本发明提供了可用于治疗男性阳ence，女性性功能障碍和肛门疾病的磷酸二酯酶抑制剂和/或一氧化氮供体。

公开(公告)号：US20070032533A1

公开(公告)日：2007-02-08

申请号：US11499770

申请日：2006-08-07

申请人： David Garvey ,  Xiong Cai ,  Xinqin Fang ,  Ramani Ranatunge ,  Shiow-Jyi Wey ,  Hai-Xiao Zhai

发明人： David Garvey ,  Xiong Cai ,  Xinqin Fang ,  Ramani Ranatunge ,  Shiow-Jyi Wey ,  Hai-Xiao Zhai

IPC分类号： A61K31/433 ,  A61K31/4245 ,  A61K31/42

CPC分类号： C07D257/04 ,  C07D401/12 ,  C07D403/10 ,  C07D403/12 ,  C07D471/04

摘要： The invention describes compositions and kits comprising at least one nitric oxide enhancing angiotensin II antagonist compound, or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitric oxide enhancing angiotensin II antagonist compound, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating cardiovascular diseases; (b) treating renovascular diseases; (c) treating diabetes; (d) treating diseases resulting from oxidative stress; (e) treating endothelial dysfunctions; (f) treating diseases caused by endothelial dysfunctions; (g) treating cirrhosis; (h) treating pre-eclampsia; (j) treating osteoporosis; (k) treating nephropathy; (l) treating peripheral vascular diseases; (m) treating portal hypertension (o) treating central nervous system disorders; (p) treating metabolic syndrome; and (q) treating hyperlipidemia. The nitric oxide enhancing angiotensin II antagonist compounds comprise at least one nitric oxide enhancing group linked to the angiotensin II antagonist compound through one or more sites such as carbon, oxygen and/or nitrogen via a bond or moiety that cannot be hydrolyzed.

摘要翻译： 本发明描述了包含至少一种一氧化氮增强型血管紧张素II拮抗剂化合物或其药学上可接受的盐的组合物和试剂盒，以及包含至少一种一氧化氮增强型血管紧张素II拮抗剂化合物和任选的至少一种一氧化氮增强化合物 和/或至少一种治疗剂。 本发明还提供了（a）治疗心血管疾病的方法; （b）治疗血管性疾病; （c）治疗糖尿病; （d）治疗由氧化应激引起的疾病; （e）治疗内皮功能障碍; （f）治疗由内皮功能障碍引起的疾病; （g）治疗肝硬化; （h）治疗先兆子痫; （j）治疗骨质疏松症; （k）治疗肾病; （l）治疗外周血管疾病; （m）治疗门静脉高压（​​o）治疗中枢神经系统疾病; （p）治疗代谢综合征; 和（q）治疗高脂血症。 一氧化氮增强型血管紧张素II拮抗剂化合物包含通过一个或多个位点如碳，氧和/或氮通过不能水解的键或部分与血管紧张素II拮抗剂化合物连接的至少一个一氧化氮增强基团。

公开(公告)号：US20080009498A1

公开(公告)日：2008-01-10

申请号：US11819514

申请日：2007-06-27

申请人： David Garvey ,  Inigo de Tejada ,  Richard Earl ,  Subhash Khanapure

发明人： David Garvey ,  Inigo de Tejada ,  Richard Earl ,  Subhash Khanapure

IPC分类号： A61K31/50 ,  A61K31/195 ,  A61K31/21 ,  A61K31/34 ,  A61K31/40 ,  A61K31/501 ,  A61P15/10 ,  A61P9/02 ,  A61P15/12 ,  A61K31/519 ,  A61K31/44 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/497

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 invention provides novel compositions containing at least one phosphodiesterase inhibitor, 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 one or more vasoactive agents. 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 diseases induced by the increased metabolism of cyclic guanosine 3′,5′-monophosphate (cGMP).

摘要翻译： 本发明提供含有至少一种磷酸二酯酶抑制剂的新组合物，以及至少一种捐赠，转移或释放一氧化氮的化合物，提高内源性内皮衍生的松弛因子水平，刺激一氧化氮的内源性合成，或是一氧化氮合酶的底物 和/或一种或多种血管活性剂。 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，以及治疗或预防环鸟苷3'，5'-单磷酸（cGMP）代谢增加所引起的疾病。

公开(公告)号：US20070037821A1

公开(公告)日：2007-02-15

申请号：US10573030

申请日：2004-09-27

申请人： David Garvey ,  Richard Earl ,  Malko Ezawa ,  Xinqin Fang ,  Ricky Gaston ,  Subhash Khanapure ,  Chia-En Lin ,  Ramani Ranatunga ,  Cheri Stevenson ,  Shiow-Jyi Wey

发明人： David Garvey ,  Richard Earl ,  Malko Ezawa ,  Xinqin Fang ,  Ricky Gaston ,  Subhash Khanapure ,  Chia-En Lin ,  Ramani Ranatunga ,  Cheri Stevenson ,  Shiow-Jyi Wey

IPC分类号： A61K31/495 ,  C07D241/04 ,  A61K31/21 ,  C07C203/02

CPC分类号： C07C271/22 ,  C07C229/24 ,  C07C237/12 ,  C07D295/185

摘要： The invention describes novel nitrosated glutamic acid compounds and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated glutamic acid compound, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated glutamic acid compound, and, and, optionally, at least one nitric oxide donor compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating cardiovascular diseases; (b) treating renovascular diseases; (c) treating diabetes; (d) treating diseases resulting from oxidative stress; (e) treating endothelial dysfunctions; (f) treating diseases caused by endothelial dysfunctions; (g) treating cirrhosis; (h) treating pre-eclampsia; (j) treating osteoporosis; (k) treating nephropathy; (l) treating diseases resulting from elevated levels of gamma-glutamyl transpeptidase and (m) the targeted delivery of compounds and nitric oxide to organs, cells or tissues containing the enzyme gamma-glutamyl transpeptidase.

摘要翻译： 本发明描述了新的亚硝酸化谷氨酸化合物及其药学上可接受的盐，以及包含至少一种亚硝酸化谷氨酸化合物和任选的至少一种一氧化氮供体和/或至少一种治疗剂的新型组合物。 本发明还提供了包含至少一种亚硝酸化谷氨酸化合物和任选的至少一种一氧化氮供体化合物和/或至少一种治疗剂的新型试剂盒。 本发明还提供了（a）治疗心血管疾病的方法; （b）治疗血管性疾病; （c）治疗糖尿病; （d）治疗由氧化应激引起的疾病; （e）治疗内皮功能障碍; （f）治疗由内皮功能障碍引起的疾病; （g）治疗肝硬化; （h）治疗先兆子痫; （j）治疗骨质疏松症; （k）治疗肾病; （l）治疗由γ-谷氨酰转肽酶水平升高引起的疾病和（m）将化合物和一氧化氮靶向递送至含有γ-谷氨酰转肽酶的器官，细胞或组织。

公开(公告)号：US20060009513A1

公开(公告)日：2006-01-12

申请号：US11135418

申请日：2005-07-13

申请人： David Garvey

发明人： David Garvey

IPC分类号： C07D493/00 ,  A61K31/353

CPC分类号： A61K31/353 ,  C07D311/22 ,  C07D311/58

摘要： The invention describes novel compositions comprising nebivolol and/or at least one metabolite of nebivolol and at least one nitric oxide donor, and, optionally, at least one antioxidant or a pharmaceutically acceptable salt thereof, and/or at least one compound used to treat cardiovascular diseases or a pharmaceutically acceptable salt thereof, and/or at least one nitrosated compound used to treat cardiovascular diseases. The compounds and compositions of the invention can also be bound to a matrix. The nitric oxide donor is a 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 may preferably be isosorbide dinitrate and/or isosorbide mononitrate. The antioxidant may preferably be a hydralazine compound or a pharmaceutically acceptable salt thereof. The invention also provides methods for treating and/or preventing vascular diseases characterized by nitric oxide insufficiency; and for treating and/or preventing Raynaud's syndrome; and for treating and/or preventing cardiovascular diseases or disorders.

摘要翻译： 本发明描述了新颖的组合物，其包含奈比洛尔和/或至少一种奈比洛尔代谢物和至少一种一氧化氮供体，以及任选的至少一种抗氧化剂或其药学上可接受的盐，和/或至少一种用于治疗心血管的化合物 疾病或其药学上可接受的盐，和/或用于治疗心血管疾病的至少一种亚硝化化合物。 本发明的化合物和组合物也可以结合到基质上。 一氧化氮供体是一种捐赠，转移或释放一氧化氮的化合物，提高内源性内皮衍生的松弛因子水平，刺激一氧化氮的内源性合成，或是一氧化氮合酶的底物，并且可以优选为硝酸异山梨酯和/或异山梨醇 一硝酸盐 抗氧化剂可优选为肼屈嗪化合物或其药学上可接受的盐。 本发明还提供治疗和/或预防以一氧化氮不足为特征的血管疾病的方法; 并用于治疗和/或预防雷诺氏综合征; 并用于治疗和/或预防心血管疾病或病症。

公开(公告)号：US20050209266A1

公开(公告)日：2005-09-22

申请号：US11135308

申请日：2005-05-24

申请人： David Garvey

发明人： David Garvey

IPC分类号： A61K20060101 ,  A61K31/395 ,  A61K31/4745 ,  C07D498/18

CPC分类号： C07D498/18

摘要： The invention describes novel nitrosated and/or nitrosylated rapamycin compounds, and novel compositions comprising at least one nitrosated and/or nitrosylated rapamycin compound, and, optionally, at least one nitric oxide donor compound. The invention also provides novel compositions comprising at least one rapamycin compound and at least one nitric oxide donor compound and/or at least one therapeutic agent. The compounds and compositions of the invention can also be bound to a matrix. The invention also provides methods for treating and/or preventing cardiovascular diseases, for the prevention of platelet aggregation and platelet adhesion caused by the exposure of blood to a medical device, for treating and/or preventing pathological conditions resulting from abnormal cell proliferation; transplantation rejections; autoimmune, inflammatory, proliferative, hyperproliferative or vascular diseases; for reducing scar tissue or for inhibiting wound contraction, particularly the prophylactic and/or therapeutic treatment of restenosis by administering nitrosated and/or nitrosylated rapamycin compounds or rapamycin compounds in combination with nitric oxide donors that are capable of releasing nitric oxide or indirectly delivering or transferring nitric oxide to targeted sites under physiological conditions.

摘要翻译： 本发明描述了新的亚硝化和/或亚硝基化的雷帕霉素化合物，以及包含至少一种亚硝化和/或亚硝基化的雷帕霉素化合物和任选的至少一种一氧化氮供体化合物的新型组合物。 本发明还提供了包含至少一种雷帕霉素化合物和至少一种一氧化氮供体化合物和/或至少一种治疗剂的新型组合物。 本发明的化合物和组合物也可以结合到基质上。 本发明还提供了治疗和/或预防心血管疾病的方法，用于预防由血液暴露于医疗器械引起的血小板聚集和血小板粘附，用于治疗和/或预防由异常细胞增殖引起的病理状况; 移植排斥 自身免疫，炎症，增殖，过度增生或血管疾病; 用于减少瘢痕组织或抑制伤口收缩，特别是通过将硝基化和/或亚硝基化的雷帕霉素化合物或雷帕霉素化合物与能够释放一氧化氮或间接递送或转移的一氧化氮供体组合的预防和/或治疗性再狭窄进行治疗 一氧化氮到生理条件下的靶点。

公开(公告)号：US20050187222A1

公开(公告)日：2005-08-25

申请号：US11109761

申请日：2005-04-20

申请人： David Garvey ,  Inigo De Tejada ,  Ricky Gaston ,  Subhash Khanapure ,  Tatiana Shelekhin ,  Tiansheng Wang

发明人： David Garvey ,  Inigo De Tejada ,  Ricky Gaston ,  Subhash Khanapure ,  Tatiana Shelekhin ,  Tiansheng Wang

IPC分类号： A61K45/06 ,  C07C381/00 ,  C07D211/62 ,  C07D233/24 ,  C07D239/95 ,  C07D401/04 ,  C07D405/12 ,  C07D459/00 ,  C07D43/02 ,  A61K31/517

CPC分类号： C07D459/00 ,  A61K45/06 ,  C07C381/00 ,  C07D211/62 ,  C07D233/24 ,  C07D239/95 ,  C07D401/04 ,  C07D405/12

摘要： The present invention describes novel nitrosated and/or nitrosylated α-adrenergic receptor antagonists, and novel compositions containing at least one nitrosated and/or nitrosylated α-adrenergic receptor antagonist, 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 are a substrate for nitric oxide synthase, and/or one or more vasoactive agents. The present invention also provides novel compositions containing at least one α-adrenergic receptor antagonist, 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 benign prostatic hyperplasia, hypertension, congestive heart failure, variant (Printzmetal) angina, glaucoma, neurodegenerative disorders, vasospastic diseases, cognitive disorders, urge incontinence, or overactive bladder, and for reversing the state of anesthesia.

摘要翻译： 本发明描述了新的亚硝化和/或亚硝基化的α-肾上腺素能受体拮抗剂，以及含有至少一种亚硝化和/或亚硝基化的α-肾上腺素能受体拮抗剂的新组合物，以及任选的一种或多种捐赠，转移或释放一氧化氮的化合物 提高内源性舒张因子的内源水平，刺激一氧化氮的内源性合成，或是一氧化氮合酶的底物和/或一种或多种血管活性剂。 本发明还提供含有至少一种α-肾上腺素能受体拮抗剂和一种或多种捐赠，转移或释放一氧化氮的化合物的新型组合物，提高内源性内皮水平的内源性松弛因子，刺激一氧化氮的内源性合成，或是一种 一氧化氮合酶的底物和/或一种或多种血管活性剂。 本发明还提供了用于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良性前列腺增生，高血压，充血性心力衰竭，变体（印刷金属）心绞痛，青光眼，神经变性 疾病，血管痉挛性疾病，认知障碍，急迫性尿失禁或膀胱过度活动，以及扭转麻醉状态。

公开(公告)号：US20050065161A1

公开(公告)日：2005-03-24

申请号：US10951778

申请日：2004-09-29

申请人： David Garvey ,  Joseph Schroeder ,  Inigo De Tejada

发明人： David Garvey ,  Joseph Schroeder ,  Inigo De Tejada

IPC分类号： A61K45/06 ,  C07C381/00 ,  C07D211/62 ,  C07D233/24 ,  C07D239/95 ,  C07D401/04 ,  C07D405/12 ,  C07D459/00 ,  A61K31/517 ,  C07D43/02

CPC分类号： C07D459/00 ,  A61K45/06 ,  C07C381/00 ,  C07D211/62 ,  C07D233/24 ,  C07D239/95 ,  C07D401/04 ,  C07D405/12

摘要： The invention is directed to nitrosated or nitrosylated alpha-adrenergic receptor antagonists, compositions comprising alpha-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. The invention also provides methods for treating female sexual dysfunctions by administering S-nitrosothiol compounds.

摘要翻译： 本发明涉及亚硝化或亚硝酰化的α-肾上腺素能受体拮抗剂，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提高内源性内皮 - 衍生松弛因子，以及治疗男性和女性性功能障碍的方法。 本发明还提供了通过施用S-亚硝基硫醇化合物治疗女性性功能障碍的方法。

公开(公告)号：US20050059665A1

公开(公告)日：2005-03-17

申请号：US10969079

申请日：2004-10-21

申请人： Subhash Khanapure ,  David Garvey ,  Richard Earl ,  Maiko Ezawa ,  Xinqin Fang ,  Ricky Gaston

发明人： Subhash Khanapure ,  David Garvey ,  Richard Earl ,  Maiko Ezawa ,  Xinqin Fang ,  Ricky Gaston

IPC分类号： A61K31/10 ,  A61K31/357 ,  A61K31/36 ,  A61K31/443 ,  A61K31/4525 ,  A61K45/00 ,  A61K45/06 ,  A61P1/04 ,  A61P1/14 ,  A61P7/02 ,  A61P7/04 ,  A61P9/10 ,  A61P11/00 ,  A61P11/06 ,  A61P11/08 ,  A61P13/02 ,  A61P13/12 ,  A61P15/04 ,  A61P15/08 ,  A61P17/00 ,  A61P17/02 ,  A61P19/02 ,  A61P21/02 ,  A61P25/28 ,  A61P27/02 ,  A61P27/16 ,  A61P29/00 ,  A61P31/04 ,  A61P35/00 ,  A61P35/02 ,  A61P37/08 ,  A61P39/02 ,  A61P43/00 ,  C07C317/14 ,  C07C317/22 ,  C07C317/24 ,  C07D317/56 ,  C07D319/08 ,  C07D319/18 ,  C07D319/20 ,  C07D405/06 ,  C07D413/06 ,  A61K31/501 ,  A61K31/21 ,  A61K31/444

CPC分类号： C07D319/08 ,  A61K45/06 ,  C07D317/56 ,  C07D319/18 ,  C07D319/20 ,  C07D405/06

摘要： The invention describes novel substituted aryl compounds that are cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or, optionally, at least one therapeutic agent, such as, steroids, nonsterodal anti-inflammatory compounds (NSAID), 5-lipoxygenase (5-LO) inhibitors, leukotriene B4 (LTB4) receptor antagonists, leukotriene A4 (LTA4) hydrolase inhibitors, 5-HT agonists, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitors, H2 antagonists, antineoplastic agents, antiplatelet agents, thrombin inhibitors, thromboxane inhibitors, decongestants, diuretics, sedating or non-sedating anti-histamines, inducible nitric oxide synthase inhibitors, opioids, analgesics, Helicobacter pylori inhibitors, proton-pump-inhibitors, isoprostane inhibitors, and mixtures thereof. The invention also provides novel kits comprising at least one COX-2 selective inhibitor, and, optionally, at least one nitric oxide donor, and/or, optionally, at least one therapeutic agent. The novel cyclooxygenase 2 selective inhibitors of the invention can be optionally nitrosated and/or nitrosylated. The invention also provides methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 selective inhibitors; for facilitating wound healing; for treating and/or preventing renal toxicity or other toxicities; for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2; and for improving the cardiovascular profile of COX-2 selective inhibitors.