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31. 发明申请

US20080220095A1 Red blood cells loaded with s-nitrosothiol and uses therefor 审中-公开
标题翻译：红细胞装载有s-nitrosothiol并用于此
公开(公告)号：US20080220095A1
公开(公告)日：2008-09-11
申请号：US12012791
申请日：2008-02-05
申请人： Jonathan S. Stamler , Joseph Bonaventura , John R. Pawloski , Timothy J. McMahon
发明人： Jonathan S. Stamler , Joseph Bonaventura , John R. Pawloski , Timothy J. McMahon
IPC分类号： A61K33/00 , A61K31/195 , A61P9/00
CPC分类号： A61K33/00 , A61K31/00 , A61K31/04 , A61K31/095 , A61K31/195 , A61K35/18 , A61K47/54 , A61K47/6445 , A61K47/6901 , C07K14/00 , G01N21/631 , G01N21/76 , G01N33/721 , Y02A50/411 , Y02A50/423
摘要： Red blood cells can be loaded with low molecular weight nitrosylating agents, such as S-nitrosothiols, to act as a delivery system for NO+ 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.
摘要翻译：红细胞可以装载低分子量亚硝酰化剂，如S-亚硝基硫醇，作为组织的NO + +组的递送系统。加载的红细胞可以用于治疗方法，其特征在于组织的异常O 2代谢，氧相关毒性，异常血管紧张度，异常红细胞粘附或异常的O < 通过红细胞递送SUB> 2 。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。

32. 发明申请

US20060024283A1 Red blood cells loaded with S-nitrosothiol and uses therefor 有权
标题翻译：装有S-亚硝基硫醇的红细胞并用于此
公开(公告)号：US20060024283A1
公开(公告)日：2006-02-02
申请号：US11179349
申请日：2005-07-12
申请人： Jonathan Stamler , Joseph Bonaventura , John Pawloski , Timothy McMahon
发明人： Jonathan Stamler , Joseph Bonaventura , John Pawloski , Timothy McMahon
IPC分类号： C12Q1/68 , A61K35/18
CPC分类号： 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
摘要： Red blood cells can be loaded with low molecular weight nitrosylating agents, such as S-nitrosothiols, to act as a delivery system for NO+ 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.
摘要翻译：红细胞可以装载低分子量亚硝酰化剂，如S-亚硝基硫醇，作为组织的NO + +组的递送系统。加载的红细胞可以用于治疗方法，其特征在于组织的异常O 2代谢，氧相关毒性，异常血管紧张度，异常红细胞粘附或异常的O < 通过红细胞递送SUB> 2 。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。

33. 发明授权

US6103690A Prevention or inhibition of pathogenic syndromes caused by nitric oxide overproduction using iron-containing hemoprotein 失效
标题翻译：使用含铁血红蛋白预防或抑制由一氧化氮过量产生引起的致病综合征
公开(公告)号：US6103690A
公开(公告)日：2000-08-15
申请号：US204392
申请日：1998-12-02
申请人： Robert G. Kilbourn , Joseph De Angelo , Joseph Bonaventura
发明人： Robert G. Kilbourn , Joseph De Angelo , Joseph Bonaventura
IPC分类号： A61K38/16 , A61K38/42 , A61P9/00 , A61P9/12
CPC分类号： A61K38/42
摘要： The invention is directed to a method for the prophylaxis or treatment of an animal for deleterious physiological effects such as systemic hypotension caused by nitric oxide production induced by a biological response modifier. Examples of such biological response modifiers include but are not limited to a cytokine and an endotoxin. The invention is also directed to a method for the treatment of septic shock.
摘要翻译：本发明涉及一种用于预防或治疗由生物反应调节剂引起的一氧化氮产生引起的全身性低血压的有害生理作用的动物的方法。这种生物反应调节剂的实例包括但不限于细胞因子和内毒素。本发明还涉及一种治疗败血性休克的方法。

34. 发明授权

US5827693A Expression of recombinant hemoglobin and hemoglobin variants in yeast 失效
标题翻译：酵母中重组血红蛋白和血红蛋白变体的表达
公开(公告)号：US5827693A
公开(公告)日：1998-10-27
申请号：US484686
申请日：1995-06-07
申请人： Joseph De Angelo , Nalini M. Motwani , Wajeeh Bajwa , Joseph Bonaventura
发明人： Joseph De Angelo , Nalini M. Motwani , Wajeeh Bajwa , Joseph Bonaventura
IPC分类号： A61K38/00 , C07K14/805 , C12N15/81 , C12P21/06 , C12N15/00 , C12N1/14
CPC分类号： C12N15/81 , C07K14/805 , A61K38/00
摘要： The invention is directed to a substantially pure mammalian globin chain or heme-binding fragment thereof. The invention is further directed to recombinant DNA vectors capable of expressing at least one globin chain or substantially homologous variant thereof in yeast. The invention also relates to methods for expressing at least one globin chain or substantially homologous variant thereof in yeast. Expressed alpha-like globin and beta-like globin chains or variants thereof may be combined with a source of heme to produce hemoglobin or a substantially homologous variant thereof. Additionally, expressed gamma-globin chains may be combined with a source of heme to produce hemoglobin or a substantially homologous variant thereof. The invention also relates to methods for expressing hemoglobin or variants thereof in yeast where the heme is produced by the yeast and ligated to globins to form hemoglobin in vivo. The hemoglobin produced by the methods of the present invention may be used in applications requiring a physiological oxygen carrier such as in blood substitute solutions and as in plasma expanders or in applications requiring a physiological oxygen carrier.
摘要翻译：本发明涉及基本上纯的哺乳动物球蛋白链或其血红素结合片段。本发明还涉及能够在酵母中表达至少一种珠蛋白链或基本上同源的变体的重组DNA载体。本发明还涉及用于在酵母中表达至少一种珠蛋白链或基本上同源的变体的方法。表达的α样球蛋白和β样球蛋白链或其变体可以与血红素来源组合以产生血红蛋白或其基本上同源的变体。此外，表达的γ-珠蛋白链可以与血红素来源组合以产生血红蛋白或其基本上同源的变体。本发明还涉及在酵母中表达血红蛋白或其变体的方法，其中血红素由酵母产生并与球蛋白结合以在体内形成血红蛋白。通过本发明的方法产生的血红蛋白可以用于需要生理氧载体的应用中，例如在血液替代溶液中，以及在等离子体扩张器中或在需要生理氧载体的应用中。

35. 发明授权

US5554638A Methods for improving therapeutic effectiveness of agents for the treatment of solid tumors and other disorders 失效
标题翻译：提高治疗实体瘤和其他疾病的药物治疗效果的方法
公开(公告)号：US5554638A
公开(公告)日：1996-09-10
申请号：US246882
申请日：1994-05-20
申请人： Mark W. Dewhirst , Robert E. Meyer , Joseph Bonaventura , Joseph DeAngelo
发明人： Mark W. Dewhirst , Robert E. Meyer , Joseph Bonaventura , Joseph DeAngelo
IPC分类号： A61N5/02 , A61F7/00 , A61K31/00 , A61K31/195 , A61K31/198 , A61K31/4045 , A61K31/42 , A61K38/16 , A61K38/42 , A61K41/00 , A61K45/06 , A61P35/00 , A61P43/00 , A61K31/22 , A61K31/415
CPC分类号： A61K41/0052 , A61K31/00 , A61K31/195 , A61K31/198 , A61K31/4045 , A61K38/42 , Y10S514/832 , Y10S514/833 , Y10S514/929 , Y10S514/93
摘要： The present invention is directed to the use of an inhibitor of NO activity, such as a nitric oxide scavenger or an NO synthase inhibitor, as an antitumor therapy to reduce tumor blood flow and oxygenation. The invention is also directed to administration of a nitric oxide scavenger or a nitric oxide synthase inhibitor to enhance the effectiveness of tumor therapy with hypoxic or acidic chemotherapeutic agents or hyperthermia. The invention is also directed to the administration of a nitric oxide synthase substrate to a subject previously administered a nitric oxide synthase inhibitor, in order to selectively inhibit tumor perfusion. In a specific example, administration of cell free hemoglobin, a nitric oxide scavenger, in conjunction with mitomycin C, a hypoxic cytotoxin, results in a significant delay in tumor growth of a human tumor xenograft in a mouse compared to mitomycin C alone. In another example, the administration of an inhibitor of nitric oxide synthase followed by the administration of a substrate of the enzyme causes a specific irreversible reduction of tumor blood flow, while normal blood flow is restored.
摘要翻译：本发明涉及NO活性抑制剂如一氧化氮清除剂或NO合成酶抑制剂作为抗肿瘤疗法以减少肿瘤血流和氧合的用途。本发明还涉及一氧化氮清除剂或一氧化氮合酶抑制剂的施用，以增强用缺氧或酸性化学治疗剂或热疗的肿瘤治疗的有效性。本发明还涉及向先前施用一氧化氮合酶抑制剂的受试者施用一氧化氮合酶底物，以选择性地抑制肿瘤灌注。在具体实例中，与丝裂霉素C单独相比，将无细胞血红蛋白（一氧化氮清除剂）与丝裂霉素C（缺氧细胞毒素）联合导致小鼠中人肿瘤异种移植物的肿瘤生长显着延迟。在另一个实例中，一氧化氮合酶抑制剂的施用随后施用酶底物导致肿瘤血流的特异性不可逆降低，同时正常血流恢复。

36. 发明授权

US5349054A Activated benzenepentacarboxylate-crosslinked low oxygen affinity hemoglobin 失效
标题翻译：活性苯甲酸交联低氧亲和力血红蛋白
公开(公告)号：US5349054A
公开(公告)日：1994-09-20
申请号：US745587
申请日：1991-08-15
申请人： Joseph Bonaventura , Marius Brouwer , Robert E. Cashon
发明人： Joseph Bonaventura , Marius Brouwer , Robert E. Cashon
IPC分类号： A61K38/00 , A61K38/42 , A61M1/36 , C07K14/805 , A61K37/00 , A61K35/14 , A61K37/02 , C07K13/00
CPC分类号： A61K38/42 , C07K14/805 , A61M1/3693 , A61M2202/0433
摘要： The invention is directed to a stroma-free tetrameric mammalian hemoglobin which is crosslinked with benzenepentacarboxylate, in which the crosslinking is carried out by a method comprising the step of activating at least two carboxylate groups of the benzenepentacarboxylate with an activating agent prior to reaction with the hemoglobin as well as methods for its production. Crosslinked stroma-free hemoglobin produced by methods of the present invention may be used in applications requiring physiological oxygen carriers such as in blood substitute solutions, or as in a plasma expander.
摘要翻译：本发明涉及一种与苯甲羧酸酯交联的无基因四聚体哺乳动物血红蛋白，其中通过包括以下步骤的方法进行交联，所述方法包括以下步骤：用活化剂在活化剂下与活化剂一起活化至少两个羧酸酯基团血红蛋白以及其生产方法。通过本发明的方法产生的交联的无基质血红蛋白可用于需要生理性氧载体的应用中，例如在血液替代溶液中，或在等离子体扩张器中。

37. 发明授权

US5296466A Inhibition of nitric oxide-mediated hypotension and septic shock with iron-containing hemoprotein 失效
标题翻译：用含铁血红蛋白抑制一氧化氮介导的低血压和败血性休克
公开(公告)号：US5296466A
公开(公告)日：1994-03-22
申请号：US838603
申请日：1992-02-19
申请人： Robert G. Kilbourn , Joseph De Angelo , Joseph Bonaventura
发明人： Robert G. Kilbourn , Joseph De Angelo , Joseph Bonaventura
IPC分类号： A61K38/16 , A61K38/42 , A61P9/00 , A61P9/12 , A61K37/02
CPC分类号： A61K38/42
摘要： The invention is directed to a method for the prophylaxis or treatment of an animal for deleterious physiological effects such as systemic hypotension caused by nitric oxide production induced by a biological response modifier. Examples of such biological response modifiers include but are not limited to a cytokine and an endotoxin. The invention is also directed to a method for the treatment of septic shock.
摘要翻译：本发明涉及一种用于预防或治疗由生物反应调节剂引起的一氧化氮产生引起的全身性低血压的有害生理作用的动物的方法。这种生物反应调节剂的实例包括但不限于细胞因子和内毒素。本发明还涉及一种治疗败血性休克的方法。

38. 发明授权

US5252630A Antifouling coating and method for using same 失效
标题翻译：防污涂料及其使用方法
公开(公告)号：US5252630A
公开(公告)日：1993-10-12
申请号：US961158
申请日：1992-10-15
申请人： Donald J. Gerhart , Dan Rittschof , Joseph Bonaventura
发明人： Donald J. Gerhart , Dan Rittschof , Joseph Bonaventura
IPC分类号： C09D5/16 , C09D5/14 , C07J43/00
CPC分类号： C09D5/1625
摘要： A method of controlling the attachment of organisms to an underwater surface is disclosed. The method comprises contacting the organisms with a compound of Formula I ##STR1## wherein R.sub.1 is hydrogen, hydroxyl, C.sub.1-C.sub.20 alkyl, C.sub.1-C.sub.20 alkoxy, C.sub.1-C.sub.20 aryl, C.sub.1-C.sub.20 alkyl aryl, or carbohydrate; R.sub.2 is hydrogen or hydroxyl, and R.sub.3 is hydrogen, or R.sub.2 and R.sub.3 together form an epoxide; R.sub.4 is hydrogen, hydroxyl, C.sub.1 -C.sub.4 alkoxy, or carboxylic acid; and L is selected from the group consisting of a moiety of Formula II, a moiety of Formula III, and a moiety of Formula IV ##STR2## wherein R.sub.5 is CH.sub.2, NH, O or S, R.sub.6 is CH.sub.2, NH, O or S, R.sub.7 is N or CH, and R.sub.8 is NH or O, and wherein the compound is optionally substituted from 1 to five times with halogen, hydroxyl, C.sub.1-C.sub.3 alkyl, or C.sub.1-C.sub.3 alkoxy groups at positions 1, 2, 4, 5, 6, 7, 8, 9, 10, 11, and 12. Antifouling coatings and cementitious compositions containing a compound of Formula I are also disclosed.
摘要翻译：公开了一种控制生物体附着到水下表面的方法。该方法包括使生物与式I化合物（I）接触，其中R 1是氢，羟基，C 1 -C 20烷基，C 1 -C 20烷氧基，C 1 -C 20芳基，C 1 -C 20烷基芳基或碳水化合物; R2是氢或羟基，R3是氢，R2和R3一起形成环氧化物; R4是氢，羟基，C1-C4烷氧基或羧酸; 并且L选自式II的部分，式III的部分和式IV的部分，其中R 5是CH 2，其中R 5是CH 2， NH，O或S，R 6是CH 2，NH，O或S，R 7是N或CH，并且R 8是NH或O，并且其中所述化合物任选地被卤素，羟基，C 1 -C 3烷基取代1至5次，或在1,2,4,5,6,7,8,9,10,11和12位的C 1 -C 3烷氧基。还公开了含有式I化合物的防结垢涂料和水泥组合物。

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