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    • 1. 发明申请
    • NITRIC OXIDE ENHANCING GLUTAMIC ACID COMPOUNDS, COMPOSITIONS AND METHODS OF USE
    • 硝酸氧化物增强谷氨酸化合物,组合物和使用方法
    • WO2007075541A3
    • 2008-11-27
    • PCT/US2006048193
    • 2006-12-19
    • NITROMED INCGARVEY DAVID S
    • GARVEY DAVID S
    • A01N65/00A61K36/00
    • A61K31/4245
    • The invention provides novel compositions and kits comprising at least one nitric oxide enhancing glutamic acid compound, or a pharmaceutically acceptable salt thereof, 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; (1) treating peripheral vascular diseases; (m) treating portal hypertension; (n) treating diseases resulting from elevated levels of gamma-glutamyl transpeptidase and (o) targeting the delivery of compounds and nitric oxide to organs, cells or tissues that contain the enzyme gamma-glutamyl transpeptidase. The nitric oxide enhancing glutamic acid compounds comprise at least one heterocyclic nitric oxide donor group and/or at least one nitroxide group.
    • 本发明提供了包含至少一种一氧化氮增强型谷氨酸化合物或其药学上可接受的盐,以及任选的至少一种一氧化氮增强化合物和/或至少一种治疗剂的新型组合物和试剂盒。 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; (1)治疗外周血管疾病; (m)治疗门静脉高压; (n)治疗由γ-谷氨酰转肽酶水平升高引起的疾病,和(o)靶向化合物和一氧化氮向含有γ-谷氨酰转肽酶的器官,细胞或组织的递送。 一氧化氮增强型谷氨酸化合物包含至少一种杂环一氧化氮供体基团和/或至少一种氮氧自由基。
    • 2. 发明申请
    • ORGANIC NITRIC OXIDE ENHANCING SALTS OF PROSTAGLANDINS, COMPOSITIONS AND METHODS OF USE
    • 有机氮氧化物增强前列腺素,组合物和使用方法
    • WO2007123818A2
    • 2007-11-01
    • PCT/US2007/008427
    • 2007-04-04
    • NITROMED, INC.GARVEY, David, S.
    • GARVEY, David, S.
    • A61K31/4245
    • C07C405/00C07C2601/08C07C2601/10C07D207/40C07D211/28C07D211/54C07D211/94C07D213/82C07D413/04C07D413/12C07D453/02
    • The invention provides compositions and kits comprising at least one organic nitric oxide enhancing salt of a prostaglandin, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods, for'(a) treating ophthalmic disorders; (b) treating cerebrovascular disorders; (c) treating cardiovascular disorders; (d) treating benign prostatic hyperplasia (BPH); (e) treating peptic ulcers; (e) treating sexual dysfunctions and (f) inducing abortions. The organic nitric oxide enhancing compounds that form salts with the prostaglandins are organic nitrates, organic nitrites, nitrosothiols, thionitrites, thionitrates, NONOates, heterocyclic nitric oxide donors and/or nitroxides. The heterocyclic nitric oxide donors are furoxans, sydnonimines, oxatriazole-5-ones and/or oxatriazole-5-imines.
    • 本发明提供了包含前列腺素的至少一种有机一氧化氮增强盐和任选的至少一种一氧化氮增强化合物和/或至少一种治疗剂的组合物和试剂盒。 本发明还提供了(a)治疗眼科疾病的方法, (b)治疗脑血管障碍; (c)治疗心血管疾病; (d)治疗良性前列腺增生(BPH); (e)治疗消化性溃疡; (e)治疗性功能障碍和(f)诱导堕胎。 与前列腺素形成盐的有机一氧化氮增强化合物是有机硝酸盐,有机亚硝酸盐,亚硝基硫醇,硫堇啶,硫堇酸盐,非硝酸盐,杂环一氧化氮供体和/或氮氧化物。 杂环一氧化氮供体是呋喃糖,苏氨酸,恶三唑-5-酮和/或氧杂三唑-5-亚胺。
    • 4. 发明申请
    • NITRIC OXIDE ENHANCING GLUTAMIC ACID COMPOUNDS, COMPOSITIONS AND METHODS OF USE
    • 硝酸氧化物增强谷氨酸化合物,组合物和使用方法
    • WO2007075541A2
    • 2007-07-05
    • PCT/US2006/048193
    • 2006-12-19
    • NITROMED, INC.GARVEY, David, S.
    • GARVEY, David, S.
    • A61K31/4245
    • A61K31/4245
    • The invention provides novel compositions and kits comprising at least one nitric oxide enhancing glutamic acid compound, or a pharmaceutically acceptable salt thereof, 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; (1) treating peripheral vascular diseases; (m) treating portal hypertension; (n) treating diseases resulting from elevated levels of gamma-glutamyl transpeptidase and (o) targeting the delivery of compounds and nitric oxide to organs, cells or tissues that contain the enzyme gamma-glutamyl transpeptidase. The nitric oxide enhancing glutamic acid compounds comprise at least one heterocyclic nitric oxide donor group and/or at least one nitroxide group.
    • 本发明提供了包含至少一种一氧化氮增强型谷氨酸化合物或其药学上可接受的盐,以及任选的至少一种一氧化氮增强化合物和/或至少一种治疗剂的新型组合物和试剂盒。 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; (1)治疗外周血管疾病; (m)治疗门静脉高压; (n)治疗由γ-谷氨酰转肽酶水平升高引起的疾病,和(o)靶向化合物和一氧化氮向含有γ-谷氨酰转肽酶的器官,细胞或组织的递送。 一氧化氮增强型谷氨酸化合物包含至少一种杂环一氧化氮供体基团和/或至少一种氮氧自由基。
    • 5. 发明申请
    • DIURETIC COMPOUNDS COMPRISING HETEROCYCLIC NITRIC OXIDE DONOR GROUPS, COMPOSITIONS AND METHODS OF USE
    • 含有杂环氧化物离子基团的化合物,组合物和使用方法
    • WO2006055542A3
    • 2006-09-08
    • PCT/US2005041321
    • 2005-11-15
    • NITROMED INCGARVEY DAVID SRANATUNGE RAMANI R
    • GARVEY DAVID SRANATUNGE RAMANI R
    • C07D285/16A61K31/41A61K31/5375A61K31/54C07D269/00C07D295/00
    • A61K31/541C07D271/08C07D413/12
    • The invention describes novel diuretic compounds comprising at least one heterocyclic nitric oxide donor group, or pharmaceutically acceptable salts thereof, and novel composition comprising at least one diuretic compound comprising at least one heterocyclic nitric oxide donor group, and optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides novel compositions and kits comprising at least one diuretic compound of the invention comprising at least one heterocyclic nitric oxide donor group, and optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating conditions resulting from excessive water and/or electrolyte retention; (b) treating cardiovascular diseases; (c) treating renovascular diseases; (d) treating diabetes; (e) treating diseases resulting from oxidatives stress; (f) treating endothelial dysfunctions; (g) treating diseases caused by endothelial dysfunctions; (h) treating cirrhosis; (j) treating pre-eclampsia; (k) treating osteoporosis; (1) treating nephropathy; (m) treating peripheral vascular diseases; (n) treating portal hypertension; (o) treating central nervous system disorders; and (p) treating sexual dysfunctions. The heterocyclic nitric oxide donors are preferably furoxans, sydnonimines, oxatriazole-5-ones and/or oxatriazole-5-imines.
    • 本发明描述了包含至少一种杂环一氧化氮供体基团的新型利尿剂化合物或其药学上可接受的盐,以及包含至少一种包含至少一种杂环一氧化氮供体基团的至少一种利尿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。 本发明还提供了包含至少一种本发明的利尿剂化合物的新型组合物和试剂盒,其包含至少一种杂环一氧化氮供体基团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)处理由过量水和/或电解质滞留导致的条件的方法; (二)治疗心血管疾病; (c)治疗血管性疾病; (d)治疗糖尿病; (e)治疗由氧化应激引起的疾病; (f)治疗内皮功能障碍; (g)治疗由内皮功能障碍引起的疾病; (h)治疗肝硬化; (j)治疗先兆子痫; (k)治疗骨质疏松症; (1)治疗肾病; (m)治疗外周血管疾病; (n)治疗门静脉高压; (o)治疗中枢神经系统疾病; 和(p)治疗性功能障碍。 杂环一氧化氮供体优选呋喃香糖,苏氨酸亚胺,氧杂三唑-5-酮和/或氧杂三唑-5-亚胺。
    • 7. 发明申请
    • CYCLOOXYGENASE- 2 SELECTIVE INHIBITORS, COMPOSITIONS AND METHODS OF USE
    • CYCLOOXYGENASE-2选择性抑制剂,组合物和使用方法
    • WO2004010945A2
    • 2004-02-05
    • PCT/US2003/023605
    • 2003-07-29
    • NITROMED, INC.GARVEY, David, S.KHANAPURE, Subhash, P.RANATUNGE, Ramani, R.RICHARDSON, Stewart, K.SCHROEDER, Joseph, D.
    • GARVEY, David, S.KHANAPURE, Subhash, P.RANATUNGE, Ramani, R.RICHARDSON, Stewart, K.SCHROEDER, Joseph, D.
    • A61K
    • C07D213/55C07D213/50C07D231/12C07D231/14
    • The invention describes novel 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 endothelium­derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one COX-2 selective inhibitor, optionally nitrosated and/or nitrosylated, 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 and/or respiratory toxicity; 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.
    • 本发明描述了新颖的环加氧酶2(COX-2)选择性抑制剂和包含至少一种环氧合酶2(COX-2)选择性抑制剂和任选地至少一种化合物的新型组合物, 或释放一氧化氮,刺激一氧化氮的内源性合成,提高内皮细胞和内皮细胞水平的内皮细胞衍生的舒张因子或是一氧化氮合酶的底物,和/或至少一种治疗剂。 本发明还提供了包含至少一种选择性抑制剂(任选亚硝化和/或亚硝基化)和任选地至少一种一氧化氮供体和/或任选地至少一种治疗剂的新型试剂盒。 本发明的新型环加氧酶2选择性抑制剂可以任选地亚硝化和/或亚硝基化。 本发明还提供治疗炎症,疼痛和发热的方法; 用于治疗和/或改善COX-2选择性抑制剂的胃肠道特性; 用于促进伤口愈合; 用于治疗和/或预防肾和/或呼吸毒性; 用于治疗和/或预防由环氧合酶-2水平升高引起的其他疾病; 并用于改善COX-2选择性抑制剂的心血管特征。
    • 10. 发明申请
    • NITROSATED AND/OR NITROSYLATED CYCLOOXYGENASE-2 SELECTIVE INHIBITORS, COMPOSITIONS AND METHODS OF USE
    • WO2003103602A3
    • 2003-12-18
    • PCT/US2003/018052
    • 2003-06-10
    • NITROMED, INC.LETTS, L., GordonGARVEY, David, S.
    • LETTS, L., GordonGARVEY, David, S.
    • A61K31/34
    • The invention describes novel nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at least one nitrosated and/or nitrosylated 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. The invention also provides novel compositions comprising at least one COX-2 selective inhibitor, that is optionally sitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent 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 and/or respiratory toxicity; 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. The invention also provides novel kits comprising at least one COX-2 selective inhibitor optionally nitrosated and/or nitrosylated, 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 are preferably 2(2-((2-chloro-6-fluorophenyl) amino)5-methylphenyl)acetic acid and nitrosated derivatives thereof.