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1. 发明授权

US5443836A Methods for protecting tissues and organs from ischemic damage 失效
标题翻译：保护组织和器官免受缺血损伤的方法
公开(公告)号：US5443836A
公开(公告)日：1995-08-22
申请号：US33310
申请日：1993-03-15
申请人： James M. Downey , Kevin Mullane
发明人： James M. Downey , Kevin Mullane
IPC分类号： A61F2/02 , A61K9/14 , A61K9/20 , A61K9/48 , A61M31/00 , C07H20060101
CPC分类号： A61K31/70 , Y10S514/936
摘要： Methods for protecting tissues and organs including the heart central nervous system, and kidney from ischemic damage are described and claimed based upon the recognition that protection against infarction is mediated by A3 rather than A1 adenosine receptors, as was previously thought, and that the receptor mediating protection in other organs and tissues has not been defined. Methods for selectively stimulating A3 adenosine receptors are described and claimed, as such selection is shown to prevent or substantially reduce cell death resulting from ischemia with or without reperfusion in humans. According to this invention, the A3 adenosine receptor is selectively stimulated by administering a compound which is an A3 adenosine receptor-selective agonist. Prevention of tissue death is also achieved by administering a compound which is a non-selective adenosine receptor agonist together with compounds that act as antagonists to the A1 and A2 adenosine receptors.
摘要翻译：基于以前认为由APC而不是A1腺苷受体介导的对梗塞的保护的认识描述和要求保护包括心脏中枢神经系统在内的组织和器官以及来自缺血性损伤的肾脏的方法，并且受体介导其他器官和组织的保护尚未定义。描述和要求保护选择性刺激A3腺苷受体的方法，因为这样的选择被证明可预防或显着减少由于在人或不伴有再灌注的局部缺血导致的细胞死亡。根据本发明，通过给予作为A3腺苷受体选择性激动剂的化合物来选择性地刺激A3腺苷受体。还通过将作为非选择性腺苷受体激动剂的化合物与作为Aβ和腺苷受体的拮抗剂的化合物一起施用来预防组织死亡。

2. 发明授权

US4353843A Preparation of nitrite esters 失效
标题翻译：亚硝酸酯的制备
公开(公告)号：US4353843A
公开(公告)日：1982-10-12
申请号：US239761
申请日：1981-03-12
申请人： Arthur R. Doumaux, Jr. , James M. Downey , Joseph P. Henry , John M. Hurt
发明人： Arthur R. Doumaux, Jr. , James M. Downey , Joseph P. Henry , John M. Hurt
IPC分类号： C07C201/04 , C07C203/00 , C07C77/00
CPC分类号： C07C201/04
摘要： A vapor phase process for making methyl or ethyl nitrite from methanol or ethanol, respectively, by reacting a nitrogen oxide composition with methanol or ethanol.
摘要翻译：通过使氮氧化物组合物与甲醇或乙醇反应，分别由甲醇或乙醇制备亚硝酸甲酯或乙酯的气相方法。

3. 发明授权

US11612615B2 Combined administration of cysteine-aspartic protease inhibitors with P2Y12 receptor antagonists protects the heart against myocardial infarction 有权
公开(公告)号：US11612615B2
公开(公告)日：2023-03-28
申请号：US16608262
申请日：2018-04-27
申请人： Jonathon P. Audia , James M. Downey , Diego Alvarez , Michael V. Cohen
发明人： Jonathon P. Audia , James M. Downey , Diego Alvarez , Michael V. Cohen
IPC分类号： A61K31/7076 , A61P9/10 , A61K31/519 , A61K38/55
摘要： The present disclosure generally pertains to methods of treating myocardial infarct involving administering a platelet anti-aggregate, a cysteine-aspartic protease inhibitor, and reperfusion therapy. In certain embodiments, the platelet anti-aggregate is at least one P2Y12 receptor antagonist or Glycoprotein IIb/IIIa inhibitor, the cysteine-aspartic protease inhibitor is selected from the group consisting of Caspase-1, 4, 5, 11 and 12 inhibitors, and reperfusion therapy is percutaneous coronary intervention. In certain embodiments, the at least one P2Y12 receptor antagonist is selected from the group consisting of cangrelor, ticagrelor, clopidogrel and prasugrel. The disclosed methods provide an improved cardioprotective effect against infarction when compared with the current standard of care.

4. 发明申请

US20210100827A1 COMBINED ADMINISTRATION OF CYSTEINE-ASPARTIC PROTEASE INHIBITORS WITH P2Y12 RECEPTOR ANTAGONISTS PROTECTS THE HEART AGAINST MYOCARDIAL INFARCTION 有权
公开(公告)号：US20210100827A1
公开(公告)日：2021-04-08
申请号：US16608262
申请日：2018-04-27
申请人： Jonathon P. Audia , James M. Downey , Diego Alvarez , Michael V. Cohen
发明人： Jonathon P. Audia , James M. Downey , Diego Alvarez , Michael V. Cohen
IPC分类号： A61K31/7076 , A61K31/519 , A61K38/55 , A61P9/10
摘要： The present disclosure generally pertains to methods of treating myocardial infarct involving administering a platelet anti-aggregate, a cysteine-aspartic protease inhibitor, and reperfusion therapy. In certain embodiments, the platelet anti-aggregate is at least one P2Y12 receptor antagonist or Glycoprotein IIb/IIIa inhibitor, the cysteine-aspartic protease inhibitor is selected from the group consisting of Caspase-1, 4, 5, 11 and 12 inhibitors, and reperfusion therapy is percutaneous coronary intervention. In certain embodiments, the at least one P2Y12 receptor antagonist is selected from the group consisting of cangrelor, ticagrelor, clopidogrel and prasugrel. The disclosed methods provide an improved cardioprotective effect against infarction when compared with the current standard of care.

5. 发明申请

US20090221649A1 Use of substituted 2-thio-3,5-dicyano-4-phenyl-6-aminopyridines for the treatment of reperfusion injury and reperfusion damage 审中-公开
标题翻译：取代的2-硫代-3,5-二氰基-4-苯基-6-氨基吡啶用于治疗再灌注损伤和再灌注损伤
公开(公告)号：US20090221649A1
公开(公告)日：2009-09-03
申请号：US11887062
申请日：2006-03-11
申请人： Thomas Krahn , Thomas Krämer , Ulrich Rosentreter , James M. Downey , Natalia Solenkova
发明人： Thomas Krahn , Thomas Krämer , Ulrich Rosentreter , James M. Downey , Natalia Solenkova
IPC分类号： A61K31/44 , C07D211/72 , A61P9/00
CPC分类号： A61K31/44
摘要： The invention relates to substituted 2-thio-3,5-dicyano-4-phenyl-6-aminopyridines of formula (I) and their use in medicaments for the prophylaxis and/or treatment of reperfusion injury and damage.
摘要翻译：本发明涉及式（I）的取代的2-硫代-3,5-二氰基-4-苯基-6-氨基吡啶及其在药物中的用途，用于预防和/或治疗再灌注损伤和损伤。

6. 发明授权

US5914242A Method for diminishing myocardial infarction using protein phosphatase inhibitors 失效
标题翻译：使用蛋白磷酸酶抑制剂减少心肌梗死的方法
公开(公告)号：US5914242A
公开(公告)日：1999-06-22
申请号：US941964
申请日：1997-10-01
申请人： Richard Eric Honkanen , James M. Downey
发明人： Richard Eric Honkanen , James M. Downey
IPC分类号： A61K31/665 , A61K38/00 , C12Q1/42 , C12Q1/00 , G01N33/53
CPC分类号： A61K31/665 , A61K38/005 , C12Q1/42
摘要： Fostriecin and a compounds structurally related to fostriecin diminish myocardial infarction and delay the onset of cell injury in an ischemic heart. There is a strong correlation between myocardial protection and the inhibition of certain serine/threonine protein phosphatases. The present invention is drawn to a method for administering fostriecin as a pharmacological compound to reduce the size of a myocardial infarction. Further, administration of fostriecin is useful also as an adjunct therapy to treatment with thrombolytic agents or angioplasty to limit the size of infarction. The most advantageous feature of the method of the present invention is that administration of fostriecin diminishes infarct volume and cell injury even when added after ischemia conditions occurred. In addition to the use of the method of the present invention for limiting damage due to myocardial infarction, the method of the present invention can be employed to delay damage associated with tissue storage for organ transplantation.
摘要翻译：福斯特因及其与fostriecin结构相关的化合物减少心肌梗塞并延缓缺血性心脏细胞损伤的发生。心肌保护与某些丝氨酸/苏氨酸蛋白磷酸酶的抑制有很强的相关性。本发明涉及一种施用作为药理化合物的骨菌素以减少心肌梗塞的大小的方法。此外，对于治疗血栓溶解剂或血管成形术来限制梗塞的大小，福斯特林的给药也可用作辅助治疗。本发明方法的最有利特征在于，即使在局部缺血病症发生后加入，三聚氰胺的施用也会降低梗死体积和细胞损伤。除了使用本发明的方法以限制由于心肌梗塞引起的损伤之外，本发明的方法可用于延迟与用于器官移植的组织储存有关的损伤。

7. 发明授权

US5573772A Methods for protecting tissues and organs from ischemic damage 失效
标题翻译：保护组织和器官免受缺血损伤的方法
公开(公告)号：US5573772A
公开(公告)日：1996-11-12
申请号：US214942
申请日：1994-03-17
申请人： James M. Downey , Kevin M. Mullane
发明人： James M. Downey , Kevin M. Mullane
IPC分类号： A61F2/02 , A61K9/14 , A61K9/20 , A61K9/48 , A61M31/00 , C07H20060101
CPC分类号： A61K31/70 , Y10S514/936
摘要： Methods for protecting tissues and organs including the heart central nervous system, and kidney from ischemic damage are described and claimed based upon the recognition that protection against infarction is mediated by A3 rather than A1 adenosine receptors, as was previously thought, and that the receptor mediating protection in other organs and tissues has not been defined. Methods for selectively stimulating A3 adenosine receptors are described and claimed, as such selection is shown to prevent or substantially reduce cell death resulting from ischemia with or without reperfusion in humans. According to this invention, the A3 adenosine receptor is selectively stimulated by administering a compound which is an A3 adenosine receptor-selective agonist. Prevention of tissue death is also achieved by administering a compound which is a non-selective adenosine receptor agonist together with compounds that act as antagonists to the A1 and A2 adenosine receptor.
摘要翻译：基于以前认为由APC而不是A1腺苷受体介导的对梗塞的保护的认识描述和要求保护包括心脏中枢神经系统在内的组织和器官以及来自缺血性损伤的肾脏的方法，并且受体介导其他器官和组织的保护尚未定义。描述和要求保护选择性刺激A3腺苷受体的方法，因为这样的选择被证明可预防或显着减少由于在人或不伴有再灌注的局部缺血导致的细胞死亡。根据本发明，通过给予作为A3腺苷受体选择性激动剂的化合物来选择性地刺激A3腺苷受体。还通过将作为非选择性腺苷受体激动剂的化合物与作为Aβ和腺苷受体的拮抗剂的化合物一起施用来预防组织死亡。

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