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公开(公告)号：EP1441712A2
公开(公告)日：2004-08-04
申请号：EP02773498.7
申请日：2002-10-10
申请人： CORNELL RESEARCH FOUNDATION, INC. , The Research Foundation of the State University of New York
IPC分类号： A61K31/155
CPC分类号： A61K31/155
摘要： remature vascular senescence is reversed or prevented in tissue or cells by contacting the tissue or cells with hydroxyguanidine.This finds application in treatment of patients with a disorder associated with elevated levels of advanced glycation end products in blood or tissue, e.g., patients with end stage renal disease or poorly controlled diabetes, and in contacting vascular tissue or cells ex vivo to prevent occurence of premature senescence.
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2.发明公开TREATMENTS BASED ON DISCOVERY THAT NITRIC OXIDE SYNTHASE IS A PARAQUAT DIAPHORASE 有权联吡啶化合物的特征为增殖细胞含有硝酸合酶疾病治疗中的用途
公开(公告)号：EP1244460A1
公开(公告)日：2002-10-02
申请号：EP00975204.9
申请日：2000-10-23
IPC分类号： A61K31/70 , A61K31/495 , A61K31/44 , A61K31/24
CPC分类号： A61K31/44 , A61K31/00 , A61K31/223 , A61K31/4425 , A61K31/444 , A61K31/4985 , A61K33/00 , A61K31/22 , A61K2300/00
摘要： Paraquat has been found to accept electrons from nitric oxide synthase (NOS) whereupon the reduced paraquat generates toxic O2- and prevents NOS from giving electrons to arginine and thereby inhibits NO production. This is generalized for compounds with a redox potential greater than nitric oxide synthase. The compounds inhibit nitric oxide synthase and kill cells including NOS by generating O¿2?- and also by depriving the cells of the NO which they need. Applications include treating paraquat-induced injury and pathologically proliferating cells (tumors, restenosis benign prostatic hypertrophy, pulmonary hypertension, infective pathogens).
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3.发明授权NITRIC OXIDE SYNTHESIS INHIBITORS FOR POTENTIATING THE ACTION OF PRESSOR AGENTS IN CERTAIN HYPOTENSIVE PATIENTS 失效一氧化氮抑制剂强化血压有效手段的效果FOR SOME HYPO TONI CORE
公开(公告)号：EP0592557B1
公开(公告)日：2000-02-02
申请号：EP92914870.8
申请日：1992-07-01
IPC分类号： A61K31/195 , A61K38/00 , A61K45/00 , A61K38/21
CPC分类号： A61K38/085 , A61K31/195 , A61K31/198 , A61K31/223 , A61K45/06 , Y10S514/93 , A61K38/217 , A61K31/135 , A61K38/20 , A61K38/191 , A61K38/19 , A61K38/04 , A61K2300/00
摘要： A method for treatment of an animal for systemic hypotension induced by internal nitric oxide production caused by endotoxin or cytokines. The method involves administering an α1 adrenergic agonist and an amount of an inhibitor of nitric oxide formation from arginine restoring vascular contractile sensitivity to $(a)1 adrenergic agonists. Preferable NG-substituted arginine (having at least one hydrogen on a guanidino amino group replaced by another atomic or molecular species). The inhibitor is administered to an animal having such induced systemic hypotension. Arginine derivative inhibitors are preferably of the L configuration and include pharmaceutically acceptable addition salts. Treatment of systemic hypotension in a patient which has been induced by chemotherapy with biologic response modifiers such as tumor necrosis factor or interleukin-2 may be likewise accomplished. Treatment of an animal for systemic hypotension induced by endotoxin, or other bacterial toxins, e.g., septic shock, may also be accomplished by treatment with α¿1? adrenergic agonists and an inhibitor such as an arginine derivative, restoring vascular contractile sensitivity to the α1 adrenergic agonists.
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4.发明公开PHARMACOTHERAPY FOR VASCULAR DYSFUNCTION ASSOCIATED WITH DEFICIENT NITRIC OXIDE BIOACTIVITY 审中-公开药物治疗血管功能障碍相关的硝酸赤字生物活性相关的
公开(公告)号：EP1351674A1
公开(公告)日：2003-10-15
申请号：EP01969029.6
申请日：2001-04-03
IPC分类号： A61K31/195 , A61K31/155
CPC分类号： A61K31/44 , A61K31/155 , A61K31/198 , A61K31/445 , A61K31/495 , A61K31/505 , A61K31/519 , A61K31/525 , A61K31/70 , A61K2300/00
摘要： A patient with a disorder involving endothelial dysfunction associated with deficient nitric oxide bioactivity, e.g., coronary artery disease, atherosclerosis, hypertension, diabetes or neurodegenerative condition stemming from ischemia and/or inflammation, is treated by administering nitric oxide bioactivity increasing agent having formula (I) wherein R?1, R2, R3 and R4¿ are the same or different and are independently selected from the group consisting hydrogen, amino, imino, alkyl, substituted alkyl, phenyl, substituted phenyl, cycloalkyl, benzyl, acyl, pyridyl, piperidyl, amino acid, lipid and carbohydrate and where R?3 and R4¿ can optionally join to form a ring. Treating agents include Nφ-hydroxyarginine and hydroxyguanidine.
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5.发明公开ARGININE ANTAGONISTS FOR INHIBITION OF SYSTEMIC HYPOTENSION ASSOCIATED WITH NITRIC OXIDE PRODUCTION OR ENDOTHELIAL DERIVED RELAXING FACTOR 失效精氨酸拮抗剂 - 氮氧化物的形成或内皮松弛因子连接系统性抑制血液压力。
公开(公告)号：EP0597831A1
公开(公告)日：1994-05-25
申请号：EP90913926.0
申请日：1990-09-13
发明人： KILBOURNE, Robert, G. , GROSS, Steven, S. , LEVI, Roberto , GRIFFITH, Owen, W. , LODATO, Robert
CPC分类号： A61K31/00 , A61K31/195 , A61K31/198 , A61K31/223 , Y10S514/93
摘要： Méthode de prophylaxie ou de traitement d'un animal souffrant d'hypotension systémique provoquée par la production interne d'oxyde nitrique. Ladite méthode comprend l'administration d'une dose thérapeutiquement efficace de certains dérivés d'arginine de manière à inhiber la formation d'oxyde d'azote à partir de l'arginine. De préférence, on administre de l'arginine NG-substitué ou un arginine disubstitué-NG,NG (au moins un hydrogène sur un groupe amin o guanidino terminal étant remplacé par une autre espèce atomique) à un animal en train de développer ou souffrant déjà de ladite hypotension systémique. Les dérivés d'arginine sont, de préférence, de la configuration L, et comprennent des sels d'addition acceptables en pharmaceutique. On accomplit ainsi chez un patient une prophylaxie ou un traitement de l'hypotension systémique provoquée par un traitement chimiothérapeutique utilisant des modificateurs de réponse biologiques tels que le facteur de nécrose tumorale ou l'interleukine-2. On peut également réaliser ainsi un traitement d'un animal souffrant d'hypotension provoquée par l'endotoxine, c'est-à-dire, le choc septique, en utilisant lesdits dérivés d'arginine.
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6.发明授权USE OF DIPYRIDINIUM COMPOUNDS FOR TREATING A DISEASE CHARACTERIZED BY PROLIFERATING CELLS CONTAINING NITRIC OXIDE SYNTHASE 有权化合物用于疾病治疗中的用途联吡啶的特征在于增殖细胞含有硝酸合酶
公开(公告)号：EP1244460B8
公开(公告)日：2010-05-19
申请号：EP00975204.9
申请日：2000-10-23
申请人： Duke University , CORNELL RESEARCH FOUNDATION, INC. , National Jewish Medical and Research Center
IPC分类号： A61K31/44 , A61K31/495 , A61K31/24 , A61K31/70 , A61P35/00 , A61P13/08 , A61P9/10 , A61P9/12
CPC分类号： A61K31/44 , A61K31/00 , A61K31/223 , A61K31/4425 , A61K31/444 , A61K31/4985 , A61K33/00 , A61K31/22 , A61K2300/00
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7.发明授权USE OF DIPYRIDINIUM COMPOUNDS FOR TREATING A DISEASE CHARACTERIZED BY PROLIFERATING CELLS CONTAINING NITRIC OXIDE SYNTHASE 有权二吡啶鎓化合物用于治疗以增加含一氧化氮合酶的细胞为特征的疾病的用途
公开(公告)号：EP1244460B1
公开(公告)日：2010-03-31
申请号：EP00975204.9
申请日：2000-10-23
IPC分类号： A61K31/44 , A61K31/495 , A61K31/24 , A61K31/70 , A61P35/00 , A61P13/08 , A61P9/10 , A61P9/12
CPC分类号： A61K31/44 , A61K31/00 , A61K31/223 , A61K31/4425 , A61K31/444 , A61K31/4985 , A61K33/00 , A61K31/22 , A61K2300/00
摘要： Paraquat has been found to accept electrons from nitric oxide synthase (NOS) whereupon the reduced paraquat generates toxic O2- and prevents NOS from giving electrons to arginine and thereby inhibits NO production. This is generalized for compounds with a redox potential greater than nitric oxide synthase. The compounds inhibit nitric oxide synthase and kill cells including NOS by generating O¿2?- and also by depriving the cells of the NO which they need. Applications include treating paraquat-induced injury and pathologically proliferating cells (tumors, restenosis benign prostatic hypertrophy, pulmonary hypertension, infective pathogens).
摘要翻译： 已经发现百草枯接受来自一氧化氮合酶（NOS）的电子，因此百草枯降低产生有毒的O2-并防止NOS将电子给予精氨酸从而抑制NO产生。 对于氧化还原电位高于一氧化氮合酶的化合物，这是一般化的。 这些化合物抑制一氧化氮合成酶并通过产生O 2 - 并且通过剥夺它们所需的NO的细胞来杀死包括NOS的细胞。 应用包括治疗百草枯诱导的损伤和病理性增殖细胞（肿瘤，再狭窄，良性前列腺肥大，肺动脉高压，感染性病原体）。
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8.发明授权ARGININE ANTAGONISTS FOR INHIBITION OF SYSTEMIC HYPOTENSION ASSOCIATED WITH NITRIC OXIDE PRODUCTION OR ENDOTHELIAL DERIVED RELAXING FACTOR 失效精氨酸拮抗剂 - 氮氧化物的形成或内皮连接系统性抑制血液压力舒张因子
公开(公告)号：EP0597831B1
公开(公告)日：1999-01-20
申请号：EP90913926.3
申请日：1990-09-13
发明人： KILBOURNE, Robert, G. , GROSS, Steven, S. , LEVI, Roberto , GRIFFITH, Owen, W. , LODATO, Robert
IPC分类号： A61K31/195
CPC分类号： A61K31/00 , A61K31/195 , A61K31/198 , A61K31/223 , Y10S514/93
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9.发明公开NITRIC OXIDE SYNTHESIS INHIBITORS FOR POTENTIATING THE ACTION OF PRESSOR AGENTS IN CERTAIN HYPOTENSIVE PATIENTS 失效一氧化氮抑制剂强化血压有效手段了一段HYPO TONI CORE的效果。
公开(公告)号：EP0592557A1
公开(公告)日：1994-04-20
申请号：EP92914870.0
申请日：1992-07-01
CPC分类号： A61K38/085 , A61K31/195 , A61K31/198 , A61K31/223 , A61K45/06 , Y10S514/93 , A61K38/217 , A61K31/135 , A61K38/20 , A61K38/191 , A61K38/19 , A61K38/04 , A61K2300/00
摘要： Procédé de traitement d'un mammifère souffrant d'hypotension générale induite par une production interne d'oxyde nitrique provoquée par des endotoxines ou des cytokines. Le procédé consiste à administrer un agoniste adrénergique alpha1 et une certaine quantité d'un inhibiteur de formation d'oxyde nitrique à partir de l'arginine, permettant de rétablir la sensibilité contractile vasculaire par rapport aux agonistes adrénergiques alpha. L'arginine utilisée de préférence est l'arginine à substitution NG (dont au moins un hydrogène sur un groupe amino guanidino est remplacé par une autre espèce moléculaire ou atomique). L'inhibiteur est administré à un animal souffrant d'une hypotension générale ainsi induite. Des inhibiteurs de dérivés d'arginine présentent de préférence une configuration L et comprennent des sels d'addition pharmaceutiquement acceptables. Il est également possible de traiter un patient souffrant d'hypotension générale induite par une chimiothéraphie effectuée à l'aide de modificateurs de réponse biologiques tels que le facteur de nécrose tumorale ou l'Interleukine-2. Il est aussi possible de soigner un mammifère souffrant d'hypotension générale induite par une endotoxine ou d'autres toxines bactériennes, par exemple provoquée par un choc septique, par l'intermédiaire d'un traitement avec des agonistes adrénergiques alpha1 et un inhibiteur tel qu'un dérivé d'arginine, qui permet de rétablir la sensibilité contractile vasculaire par rapport aux agonistes adrénergiques alpha1.
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