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    Therapies using hemoproteins
    4.
    发明申请
    Therapies using hemoproteins 有权
    使用血液蛋白的疗法

    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。

    Novel polymers for delivering nitric oxide in vivo
    5.
    发明申请
    Novel polymers for delivering nitric oxide in vivo 失效
    用于在体内递送一氧化氮的新型聚合物

    公开(公告)号：US20030078365A1

    公开(公告)日：2003-04-24

    申请号：US10164366

    申请日：2002-06-05

    Applicant: Duke University

    Inventor： Jonathan S. Stamler ,  Eric J. Toone ,  Richard S. Stack

    IPC: C08G075/00

    CPC classification number: A61K31/785 ,  A61K47/61 ,  A61K47/6951 ,  A61L29/10 ,  A61L29/16 ,  A61L31/10 ,  A61L31/16 ,  A61L33/068 ,  A61L33/08 ,  A61L2300/114 ,  A61L2300/416 ,  A61L2300/42 ,  B82Y5/00 ,  C08B37/0012 ,  C08G75/00 ,  C08L5/16 ,  C09D105/16 ,  G06F19/00 ,  Y10T428/1393

    Abstract: Disclosed are novel polymers derivatized with at least one nullSNO group per 1200 atomic mass unit of the polymer. In one embodiment, the S-nitrosylated polymer has stabilized nullS-nitrosyl groups. In another embodiment the S-nitrosylated polymer prepared by polymerizing a compound represented by the following structural formula: 1 R is an organic radical. Each Xnull is an independently chosen aliphatic group or substituted aliphatic group. Preferably, each Xnull is the same and is a C2-C6 alkylene group, more preferably nullCH2null, nullCH2CH2null, nullCH2CH2CH2null or nullCH2CH2CH2CH2null. p and m are independently a positive integer such that pnullm is greater than two. The polymers of the present invention can be used to coat medical devices to deliver nitric oxide in vivo to treatment sites.

    Abstract translation: 公开了每聚合物的每1200原子质量单位衍生自至少一个-SNO基团的新型聚合物。 在一个实施方案中，S-亚硝基化聚合物具有稳定的-S-亚硝酰基。 在另一个实施方案中，通过聚合由以下结构式表示的化合物制备的S-亚硝基化聚合物：R是有机基团。 每个X'是独立选择的脂族基团或取代的脂族基团。 优选地，每个X'相同且为C2-C6亚烷基，更优选为-CH2-，-CH2CH2-，-CH2CH2CH2-或-CH2CH2CH2CH2-。 p和m独立地为正整数，使得p + m大于2。 本发明的聚合物可用于涂覆医疗装置以将体内的一氧化氮输送到治疗部位。

    Treating pulmonary disorders with gaseous agent causing repletion of GSNO
    6.
    发明申请
    Treating pulmonary disorders with gaseous agent causing repletion of GSNO 失效
    用导致GSNO补充的气体药物治疗肺部疾病

    公开(公告)号：US20010012834A1

    公开(公告)日：2001-08-09

    申请号：US09782077

    申请日：2001-02-14

    Applicant: DUKE UNIVERSITY

    Inventor： Jonathan S. Stamler

    IPC: A61K033/04 ,  A61K033/00

    CPC classification number: A61K31/375 ,  A61K31/197 ,  A61K31/21 ,  A61K31/221 ,  A61K33/00 ,  A61K33/04 ,  A61K45/06 ,  A61M2202/0275 ,  Y10S514/826 ,  Y10S514/851 ,  Y10S514/929 ,  Y10S514/958 ,  Y10S514/959 ,  A61K2300/00

    Abstract: Pulmonary disorders in which the GSNO pool or glutathione pool in the lung is depleted and where reactive oxygen species in lung are increased, are treated by delivering into the lung as a gas, agent causing repletion or increase of the GSNO pool or protection against toxicity and does so independently of reaction with oxygen. Agents include ethyl nitrite, NOCl, NOBr, NOF, NOCN, N2O3, HNO, and H2S. Optionally, N-acetylcysteine, ascorbate, H2S or HNO is administered in addition to other GSNO repleting agent to potentiate the effect of said agent.

    Abstract translation: 其中肺中的GSNO池或谷胱甘肽池被耗尽并且肺中的活性氧物质增加的肺部疾病通过作为气体递送到肺中，导致GSNO池的补充或增加或防止毒性的药物， 独立于与氧的反应。 试剂包括亚硝酸乙酯，NOCl，NOBr，NOF，NOCN，N2O3，HNO和H2S。 任选地，除了其他GSNO补充剂之外还施用N-乙酰半胱氨酸，抗坏血酸盐，H 2 S或HNO以增强所述药剂的作用。

    Use of a blood-flow decrease preventing agent in conjunction with insufflating gas
    8.
    发明申请
    Use of a blood-flow decrease preventing agent in conjunction with insufflating gas 有权
    使用血流减少预防剂与吸入气体联合使用

    公开(公告)号：US20030032917A1

    公开(公告)日：2003-02-13

    申请号：US09919931

    申请日：2001-08-02

    Applicant: DUKE UNIVERSITY

    Inventor： Jonathan S. Stamler

    IPC: A61M031/00

    CPC classification number: A61K33/00 ,  A61B17/34 ,  A61B17/3474 ,  A61K31/04 ,  A61K31/21 ,  A61M31/00 ,  A61M2202/02 ,  A61M2210/1017 ,  A61K2300/00

    Abstract: A blood-flow decrease preventing agent is used to negate or reduce the decreased oxygen delivery in abdominal organs caused by insufflating gas. Preferably a gas is delivered into the abdominal cavity consisting essentially of the insufflating gas and the blood-flow decrease preventing agent. Very preferably, a gas is used consisting essentially of carbon dioxide as the insufflating gas and ethyl nitrite as the blood-flow to abdominal organ decrease preventing agent.

    Abstract translation: 使用血流减少预防剂来抵消或减少由吹入气体引起的腹部器官中的氧传递减少。 优选地，将气体输送到基本上由吹入气体和血液流减少预防剂组成的腹腔中。 非常优选地，使用气体主要由二氧化碳作为吹入气体和亚硝酸乙酯作为血液流向腹部器官减少预防剂。

    Red blood cells loaded with S-nitrosothiol and uses therefor
    9.
    发明申请
    Red blood cells loaded with S-nitrosothiol and uses therefor 失效
    装有S-亚硝基硫醇的红细胞并用于此

    公开(公告)号：US20030008300A1

    公开(公告)日：2003-01-09

    申请号：US10045603

    申请日：2001-10-23

    Applicant: Duke University

    Inventor： Jonathan S. Stamler ,  Joseph Bonaventura ,  John R. Pawloski ,  Timothy J. McMahon

    IPC: C12Q001/68

    CPC classification number: A61K31/00 ,  A61K31/04 ,  A61K31/095 ,  A61K31/195 ,  A61K33/00 ,  A61K38/1816 ,  A61K47/54 ,  A61K47/6445 ,  A61K47/6901 ,  C07K14/00 ,  G01N21/631 ,  G01N21/76 ,  G01N33/721

    Abstract: Red blood cells can be loaded with low molecular weight nitrosylating agents, such as S-nitrosothiols, to act as a delivery system for NOnull groups to tissues. Loaded red blood cells can be used in methods of therapy for conditions which are characterized by abnormal O2 metabolism of tissues, oxygen-related toxicity, abnormal vascular tone, abnormal red blood cell adhesion, or abnormal O2 delivery by red blood cells. Such treatment of red blood cells can be extended to in vivo therapies, with the object to achieve an increase in the ratio of red blood cell S-nitrosothiol to hemoglobin.

    Abstract translation: 红细胞可以装载低分子量亚硝酰化剂，如S-亚硝基硫醇，作为NO +组组织的递送系统。 加载的红细胞可用于以组织异常氧代谢，氧相关毒性，异常血管紧张，红细胞异常粘附或红细胞异常氧传递为特征的病症的治疗方法。 红细胞的这种治疗可以延伸到体内治疗，其目的是实现红细胞S-亚硝基硫醇与血红蛋白的比例的增加。

    Stable no-delivering compounds
    10.
    发明申请
    Stable no-delivering compounds 有权
    稳定的不输送化合物

    公开(公告)号：US20040019105A1

    公开(公告)日：2004-01-29

    申请号：US10387116

    申请日：2003-03-11

    Applicant: Duke University

    Inventor： Eric J. Toone ,  Jonathan S. Stamler

    IPC: A61K031/21 ,  C07C381/00

    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.

    Abstract translation: 公开了包含稳定的S-亚硝酰基和游离醇或游离巯基的新型NO释放化合物。 还公开了制备释放NO的化合物的方法。 该方法包括使多硫醇或硫代醇与亚硝酰化剂反应。 还公开了涂覆有所公开的化合物的医疗装置，通过利用医疗装置和灭菌表面的方法将NO递送到受试者的治疗部位的方法。

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