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1. 发明授权

US07179791B2 Inhibiting GS-FDH to modulate NO bioactivity 有权
标题翻译：抑制GS-FDH调节NO生物活性
公开(公告)号：US07179791B2
公开(公告)日：2007-02-20
申请号：US09757610
申请日：2001-01-11
申请人： Jonathan S. Stamler , Limin Liu , Alfred Hausladen , Raphael Nudelman
发明人： Jonathan S. Stamler , Limin Liu , Alfred Hausladen , Raphael Nudelman
IPC分类号： A61K38/00 , A61K31/34 , A61K31/195
CPC分类号： A61K38/063 , A61K31/365 , A61K31/7056 , Y10S514/824
摘要： Patients needing NO donor therapy or inhibition of pathologically proliferating cells or increased NO bioactivity are treated with a therapeutically effective amount of an inhibitor of glutathione-dependent formaldehyde dehydrogenase.
摘要翻译：需要NO供体治疗或抑制病理增殖细胞或增加NO生物活性的患者用治疗有效量的谷胱甘肽依赖性甲醛脱氢酶抑制剂治疗。

2. 发明授权

US07112563B2 Therapies using hemoproteins 有权
标题翻译：使用血液蛋白的疗法
公开(公告)号：US07112563B2
公开(公告)日：2006-09-26
申请号：US09756478
申请日：2001-01-08
申请人： Jonathan S. Stamler , Alfred Hausladen
发明人： Jonathan S. Stamler , Alfred Hausladen
IPC分类号： A61K38/16 , A61K38/00
CPC分类号： A61K38/50 , A61K38/41 , A61K38/42 , A61K31/70 , A61K2300/00
摘要： Herein it is shown that hemoproteins (e.g., Ascaris hemoglobin, myoglobin, flavohemoglobins) have NO-consuming and deoxygenase activities. The invention provides a method of reducing the concentration of oxygen and/or nitric oxide in a mammal. The method of the invention comprises administering a therapeutically effective amount of a hemoprotein having NO-activated deoxygenase activity or an enzymatically active fragment thereof to a mammal. The method can be used to treat a mammal having pathologically proliferating cells, such as a tumor. In one embodiment, the hemoprotein is administered to reduce the oxygen concentration of a tumor. In another embodiment, the hemoprotein is administered together with a cytotoxic agent to treat a mammal having a tumor. The invention also provides a method of enzymatically generating toxic reactive oxygen species in a mammal for therapeutic purposes. The method comprises administering a therapeutically effective amount of a hemoprotein to a mammal. The invention also provides a composition comprising a hemoprotein having deoxygenase activity or an enzymatically active fragment thereof and a physiologically acceptable carrier. In one embodiment, the composition further comprises a cytotoxic agent and/or a reducing agent. The invention further provides a method of treating a mammal infected with Ascaris sp., comprising administering to said mammal a therapeutically effective amount of an inhibitor of NO synthase. The NO-consuming activity of a hemoprotein (e.g., a flavohemoglobin) can be used in a treatment where constriction of blood vessels is desirable, or where it is otherwise desirable to reduce NO concentration, as in inflammation.
摘要翻译：在本文中，显示出血蛋白（例如蛔虫血红蛋白，肌红蛋白，黄素血红蛋白）具有消耗NO和脱氧酶的活性。本发明提供了降低哺乳动物氧和/或一氧化氮浓度的方法。本发明的方法包括向哺乳动物施用治疗有效量的具有NO活化的脱氧酶活性的血液蛋白或其酶活性片段。该方法可用于治疗具有病理增殖细胞（例如肿瘤）的哺乳动物。在一个实施方案中，施用血液蛋白以降低肿瘤的氧浓度。在另一个实施方案中，血细胞蛋白与细胞毒素一起施用以治疗具有肿瘤的哺乳动物。本发明还提供了一种为了治疗目的而在哺乳动物中酶促产生毒性活性氧的方法。该方法包括向哺乳动物施用治疗有效量的血蛋白。本发明还提供包含具有脱氧酶活性的血蛋白或其酶活性片段和生理学上可接受的载体的组合物。在一个实施方案中，组合物还包含细胞毒性剂和/或还原剂。本发明还提供了治疗感染蛔虫感染的哺乳动物的方法，其包括向所述哺乳动物施用治疗有效量的NO合酶抑制剂。血红蛋白（例如，黄素血红蛋白）的消耗消耗的活性可以用于需要血管收缩的处理，或者在炎症中如减少NO浓度是其它方面。

3. 发明申请

US20120245116A1 Inhibiting GS-FDH to Modulate No Bioactivity 审中-公开
标题翻译：抑制GS-FDH调节无生物活性
公开(公告)号：US20120245116A1
公开(公告)日：2012-09-27
申请号：US13491752
申请日：2012-06-08
申请人： Jonathan S. Stamler , Limin Liu , Alfred Hausladen , Raphael Nudelman
发明人： Jonathan S. Stamler , Limin Liu , Alfred Hausladen , Raphael Nudelman
IPC分类号： A61K31/7056 , A61K31/197 , A61K31/343
CPC分类号： A61K38/063 , A61K31/365 , A61K31/7056 , Y10S514/824
摘要： Patients needing NO donor therapy or inhibition of pathologically proliferating cells or increased NO bioactivity are treated with a therapeutically effective amount of an inhibitor of glutathione-dependent formaldehyde dehydrogenase.
摘要翻译：需要NO供体治疗或抑制病理增殖细胞或增加NO生物活性的患者用治疗有效量的谷胱甘肽依赖性甲醛脱氢酶抑制剂治疗。

4. 发明申请

US20070111949A1 Inhibiting GS-FDH to modulate no bioactivity 失效
标题翻译：抑制GS-FDH调节无生物活性
公开(公告)号：US20070111949A1
公开(公告)日：2007-05-17
申请号：US11648406
申请日：2006-12-29
申请人： Jonathan Stamler , Limin Liu , Alfred Hausladen , Raphael Nudelman
发明人： Jonathan Stamler , Limin Liu , Alfred Hausladen , Raphael Nudelman
IPC分类号： A61K38/05 , A61K31/365
CPC分类号： A61K38/063 , A61K31/365 , A61K31/7056 , Y10S514/824
摘要： Patients needing NO donor therapy or inhibition of pathologically proliferating cells or increased NO bioactivity are treated with a therapeutically effective amount of an inhibitor of glutathione-dependent formaldehyde dehydrogenase.
摘要翻译：需要NO供体治疗或抑制病理增殖细胞或增加NO生物活性的患者用治疗有效量的谷胱甘肽依赖性甲醛脱氢酶抑制剂治疗。

5. 发明申请

US20100015121A1 INHIBITING GS-FDH TO MODULATE NO BIOACTIVITY 有权
标题翻译：抑制GS-FDH来调节无生物活性
公开(公告)号：US20100015121A1
公开(公告)日：2010-01-21
申请号：US12566006
申请日：2009-09-24
申请人： Jonathan S. Stamler , Limin Liu , Alfred Hausladen , Raphael Nudelman
发明人： Jonathan S. Stamler , Limin Liu , Alfred Hausladen , Raphael Nudelman
IPC分类号： A61K38/44 , A61K38/06 , A61P11/00 , A61P15/10 , A61K31/34 , A61P9/10 , A61P7/00 , A61P1/16 , A61P9/00
CPC分类号： A61K38/063 , A61K31/365 , A61K31/7056 , Y10S514/824
摘要： Patients needing NO donor therapy or inhibition of pathologically proliferating cells or increased NO bioactivity are treated with a therapeutically effective amount of an inhibitor of glutathione-dependent formaldehyde dehydrogenase.
摘要翻译：需要NO供体治疗或抑制病理增殖细胞或增加NO生物活性的患者用治疗有效量的谷胱甘肽依赖性甲醛脱氢酶抑制剂治疗。

6. 发明授权

US07615535B2 Inhibiting GS-FDH to modulate no bioactivity 失效
标题翻译：抑制GS-FDH调节无生物活性
公开(公告)号：US07615535B2
公开(公告)日：2009-11-10
申请号：US11648406
申请日：2006-12-29
申请人： Jonathan S. Stamler , Limin Liu , Alfred Hausladen , Raphael Nudelman
发明人： Jonathan S. Stamler , Limin Liu , Alfred Hausladen , Raphael Nudelman
IPC分类号： A61K38/05
CPC分类号： A61K38/063 , A61K31/365 , A61K31/7056 , Y10S514/824
摘要： Patients needing NO donor therapy or inhibition of pathologically proliferating cells or increased NO bioactivity are treated with a therapeutically effective amount of an inhibitor of glutathione-dependent formaldehyde dehydrogenase.
摘要翻译：需要NO供体治疗或抑制病理增殖细胞或增加NO生物活性的患者用治疗有效量的谷胱甘肽依赖性甲醛脱氢酶抑制剂治疗。

7. 发明授权

US08217006B2 Inhibiting GS-FDH to modulate no bioactivity 有权
标题翻译：抑制GS-FDH调节无生物活性
公开(公告)号：US08217006B2
公开(公告)日：2012-07-10
申请号：US12566006
申请日：2009-09-24
申请人： Jonathan S. Stamler , Limin Liu , Alfred Hausladen , Raphael Nudelman
发明人： Jonathan S. Stamler , Limin Liu , Alfred Hausladen , Raphael Nudelman
IPC分类号： A61K38/44
CPC分类号： A61K38/063 , A61K31/365 , A61K31/7056 , Y10S514/824
摘要： Patients needing NO donor therapy or inhibition of pathologically proliferating cells or increased NO bioactivity are treated with a therapeutically effective amount of an inhibitor of glutathione-dependent formaldehyde dehydrogenase.
摘要翻译：需要NO供体治疗或抑制病理增殖细胞或增加NO生物活性的患者用治疗有效量的谷胱甘肽依赖性甲醛脱氢酶抑制剂治疗。

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