公开(公告)号：US20020099330A1

公开(公告)日：2002-07-25

申请号：US10026851

申请日：2001-12-18

Applicant: Duke University Medical Center

Inventor： Eric J. Toone ,  Jonathan S. Stamler

IPC: A61M031/00 ,  C07C381/10 ,  A61K031/215

CPC classification number: A61L2/23 ,  A61L2/20 ,  A61L29/16 ,  A61L2300/114 ,  A61L2300/216 ,  C07C381/00

Abstract: Disclosed are novel NO-releasing compounds which comprise a stabilized S-nitrosyl group and a free alcohol or a free thiol group. Also disclosed is a method of preparing the NO-releasing compounds. The method comprises reacting a polythiol or a thioalcohol with a nitrosylating agent. Also disclosed are medical devices coated with the disclosed compounds, methods of delivering NO to treatments sites in a subject by utilizing the medical devices and methods of sterilizing surfaces.

公开(公告)号：US20010031727A1

公开(公告)日：2001-10-18

申请号：US09756478

申请日：2001-01-08

Applicant: Duke University Medical Center

Inventor： Jonathan S. Stamler ,  Alfred Hausladen

IPC: A61K038/42

CPC classification number: A61K38/50 ,  A61K38/41 ,  A61K38/42 ,  A61K31/70 ,  A61K2300/00

Abstract: 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.

Abstract translation: 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。