公开(公告)号：US08466110B2

公开(公告)日：2013-06-18

申请号：US13449932

申请日：2012-04-18

申请人： Mark W. Dewhirst ,  Jonathan S. Stamler ,  Timothy J. McMahon ,  Pierre Sonveaux

发明人： Mark W. Dewhirst ,  Jonathan S. Stamler ,  Timothy J. McMahon ,  Pierre Sonveaux

IPC分类号： A61K38/00

CPC分类号： A61K38/1709 ,  A61K31/21 ,  A61K33/00 ,  A61K35/18 ,  A61K38/00 ,  A61K38/42 ,  A61K45/06 ,  A61K47/08 ,  A61K47/16 ,  A61K47/6445 ,  A61K2300/00

摘要： The presently disclosed subject matter provides methods for increasing perfusion in hypoxic regions of tissues in subjects. Also provided are methods for treating diseases and/or disorders associated with hypoxia in subjects, methods for increasing sensitivity of tumors to radiation and/or chemotherapy treatments, methods for delaying tumor growth in subjects, and methods for inhibiting tumor blood vessel growth in subjects. In some embodiments, the presently disclosed methods involve administering to subjects in need thereof a first composition selected from the group consisting of a nitrosylated hemoglobin and an agent that induces nitrosylation of endogenous hemoglobin in the subject and a second composition comprising a hyperoxic gas. In some embodiments, the presently disclosed methods also include treating a tumor with radiation therapy, chemotherapy, photodynamic therapy, immunotherapy, or combinations thereof. Also provided are inhalable gases that can be employed in the presently disclosed methods.

公开(公告)号：US20120121720A1

公开(公告)日：2012-05-17

申请号：US13256954

申请日：2010-03-31

申请人： Jonathan S. Stamler ,  Liang Xie

发明人： Jonathan S. Stamler ,  Liang Xie

IPC分类号： A61K31/225 ,  A61K31/713 ,  A61K38/10 ,  A61K31/403 ,  A61K33/00 ,  A61P11/06 ,  A61P11/00 ,  A61P9/00 ,  A61P7/10 ,  A61P9/12 ,  A61P3/00 ,  A61P39/04 ,  A61P9/04 ,  A61P9/06 ,  A61P9/10 ,  A61P27/06 ,  A61P25/06 ,  A61P25/08 ,  A61P25/22 ,  A61K35/14 ,  A61K35/28 ,  A61P7/06 ,  A61K38/06

CPC分类号： A61K31/00 ,  A61K31/198 ,  A61K45/06

摘要： This present invention relates to methods, compositions, and kits useful for treating a patient having or at risk for developing a disorder associated with decreased expression of β2 adrenergic receptors or need for increased 132 adrenergic receptor activity.

摘要翻译： 本发明涉及可用于治疗患有或具有发展与减少的二肾上腺素能受体表达相关的病症或有风险的患者或需要增加132肾上腺素能受体活性的患者的方法，组合物和试剂盒。

公开(公告)号：US20100266581A1

公开(公告)日：2010-10-21

申请号：US12723282

申请日：2010-03-12

申请人： JONATHAN S. STAMLER ,  LIMIN LIU

发明人： JONATHAN S. STAMLER ,  LIMIN LIU

IPC分类号： A61K39/395 ,  A61K31/155 ,  A61P25/16 ,  A61P25/28 ,  A61P9/10 ,  A61P35/00 ,  A61P9/12 ,  A61K31/7088 ,  A61K31/713 ,  A61K31/416 ,  A61K31/198

CPC分类号： G01N33/573 ,  A01K67/0276 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/035 ,  A61K31/155 ,  A61K31/41 ,  A61K38/44 ,  C12N9/0008 ,  C12N15/8509 ,  C12Q1/26 ,  C12Y102/01046 ,  G01N2333/90212 ,  G01N2800/00 ,  A61K2300/00

摘要： Disclosed herein are methods and compositions for modulating the levels and/or activity of S-nitrosoglutathione reductase (GSNOR) in vivo or in vitro. Specifically disclosed are GSNOR deletion constructs, host cells and non-human mammals comprising GSNOR deletions, and methods of screening employing GSNOR deletion mutants. Also specifically disclosed are reagents and procedures for measuring, monitoring, or altering GSNOR levels or activity (as well as nitric oxide and S-nitrosothiol levels) in connection with various medical conditions.

摘要翻译： 本文公开了用于在体内或体外调节S-亚硝基谷胱甘肽还原酶（GSNOR）的水平和/或活性的方法和组合物。 具体公开的是GSNOR缺失构建体，宿主细胞和包含GSNOR缺失的非人哺乳动物，以及使用GSNOR缺失突变体进行筛选的方法。 还具体公开了用于测量，监测或改变与各种医学状况有关的GSNOR水平或活性（以及一氧化氮和S-亚硝基硫醇水平）的试剂和程序。

公开(公告)号：US07776925B2

公开(公告)日：2010-08-17

申请号：US10980801

申请日：2004-11-04

申请人： Jonathan S. Stamler ,  Zhiqiang Chen ,  Thomas Munzel

发明人： Jonathan S. Stamler ,  Zhiqiang Chen ,  Thomas Munzel

IPC分类号： A61K31/095 ,  A61K31/045

CPC分类号： A61K31/41 ,  A61K31/04 ,  A61K31/52

摘要： A patient in need of nitroglycerin therapy is treated with nitroglycerin and agent that prevents inhibition of or reverses inhibition of mtALDH and/or the generation of reactive oxygen species from mitochondria, e.g., a mitochondrial antioxidant which is not a reducing agent or a dithiol, e.g., ebselen or uric acid. Nitroglycerin dosage can be regulated and inhibiting agent dosage can be regulated and tolerance postponed by monitoring blood level of active mtALDH and dosing in response to determined level of active mtALDH.

摘要翻译： 需要硝酸甘油治疗的患者用硝酸甘油和药剂治疗，其防止抑制或逆转mtALDH的抑制和/或从线粒体产生活性氧，例如不是还原剂或二硫醇的线粒体抗氧化剂，例如 ，依勃硒或尿酸。 通过监测活性mtALDH的血液水平和给药以响应确定的活性mtALDH水平，可以调节硝酸甘油剂量并且可以调节抑制剂剂量并进行耐受性推迟。

公开(公告)号：US20100010019A1

公开(公告)日：2010-01-14

申请号：US12554249

申请日：2009-09-04

申请人： Jonathan S. Stamler ,  Eric J. Toone ,  Joshua M. Hare

发明人： Jonathan S. Stamler ,  Eric J. Toone ,  Joshua M. Hare

IPC分类号： A61K31/519 ,  A61P29/00

CPC分类号： C07D487/04 ,  A61K31/519

摘要： A reactive oxygen generating enzyme inhibitor with NO donor bioactivity, e.g., nitrated allopurinol, is useful to treat heart failure, stable angina, ischemic disorder, ischemic reperfusion injury, atherosclerosis, sickle cell disease, diabetes, Alzheimer's disease, Parkinson's disease, ALS and asthma and to obtain proper contraction of heart, skeletal and smooth muscle.

摘要翻译： 具有NO供体生物活性的活性氧产生酶抑制剂，例如硝化别嘌呤醇，可用于治疗心力衰竭，稳定性心绞痛，缺血性障碍，缺血再灌注损伤，动脉粥样硬化，镰状细胞病，糖尿病，阿尔茨海默病，帕金森病，ALS和哮喘 并获得心脏，骨骼和平滑肌的适当收缩。

公开(公告)号：US07625907B2

公开(公告)日：2009-12-01

申请号：US11430986

申请日：2006-05-10

申请人： Jonathan S. Stamler ,  Eric J. Toone ,  Joshua M. Hare

发明人： Jonathan S. Stamler ,  Eric J. Toone ,  Joshua M. Hare

IPC分类号： A61K31/519 ,  A61P9/10 ,  C07D487/04

CPC分类号： C07D487/04 ,  A61K31/519

摘要： A reactive oxygen generating enzyme inhibitor with NO donor bioactivity, e.g., nitrated allopurinol, is useful to treat heart failure, stable angina, ischemic disorder, ischemic reperfusion injury, atherosclerosis, sickle cell disease, diabetes, Alzheimer's disease, Parkinson's disease, ALS and asthma and to obtain proper contraction of heart, skeletal and smooth muscle.

摘要翻译： 具有NO供体生物活性的活性氧产生酶抑制剂，例如硝化别嘌呤醇，可用于治疗心力衰竭，稳定性心绞痛，缺血性障碍，缺血再灌注损伤，动脉粥样硬化，镰状细胞病，糖尿病，阿尔茨海默病，帕金森病，ALS和哮喘 并获得心脏，骨骼和平滑肌的适当收缩。

公开(公告)号：US20090232909A1

公开(公告)日：2009-09-17

申请号：US12082698

申请日：2008-04-11

申请人： Jonathan S. Stamler ,  Andrew J. Gow ,  David J. Singel

发明人： Jonathan S. Stamler ,  Andrew J. Gow ,  David J. Singel

IPC分类号： A61K33/00 ,  C07K14/435

CPC分类号： G01N33/721 ,  A61K31/00 ,  A61K31/04 ,  A61K31/12 ,  A61K31/122 ,  A61K31/18 ,  A61K31/255 ,  A61K31/26 ,  A61K31/381 ,  A61K31/382 ,  A61K31/433 ,  A61K31/465 ,  A61K31/519 ,  A61K33/22 ,  A61K33/26 ,  A61K33/42 ,  A61K35/18 ,  A61K38/42 ,  G01N2333/805 ,  A61K2300/00

摘要： NO preferentially binds to the minor population of the hemoglobin's vacant hemes in a cooperative manner, nitrosylates hemoglobin thiols, or reacts with liberated superoxide in solution. The distribution of minor forms of hemoglobin can be tested and the results can be used to predict whether a composition of hemoglobin will scavenge, load, eliminate, or donate NO. Hemoglobin thus serves to regulate the chemistry of NO. SNO-hemoglobin transfers NO equivalents to the red blood cell anion transport protein AE1, which serves to export NO from red blood cells. Regulation of AE1 function is the basis for methods of therapy to affect levels of NO or its biological equivalent.

摘要翻译： NO以合作的方式优先结合血红蛋白的空白血小板的次要群体，亚硝酰化血红蛋白硫醇，或与溶液中释放的超氧化物反应。 可以测试次要形式的血红蛋白的分布，结果可用于预测血红蛋白组成是否会清除，加载，消除或捐赠NO。 因此，血红蛋白用于调节NO的化学。 SNO-血红蛋白转移到红细胞阴离子转运蛋白AE1的NO当量，用于从红细胞中输出NO。 AE1功能的调节是影响NO或其生物学等效水平的治疗方法的基础。

公开(公告)号：US20080145873A1

公开(公告)日：2008-06-19

申请号：US12037411

申请日：2008-02-26

申请人： Jonathan S. STAMLER

发明人： Jonathan S. STAMLER

IPC分类号： G01N33/53

CPC分类号： C12Q1/6809 ,  G01N33/5091 ,  G01N33/6803 ,  Y10S977/924

摘要： Genomic actions and/or proteomic interactions for pathophysiological processes and for physiological processes are determined at associated redox state conditions. Protein interactions are correlated with oxygen tensions. Identification of markers for disease including epitopes is effected in the presence of simulated redox state perturbations. Screening for previously unknown receptors and activating ligands is carried out in the presence of alteration of redox state.

摘要翻译： 在相关的氧化还原状态下测定病理生理过程和生理过程的基因组作用和/或蛋白质组学相互作用。 蛋白质相互作用与氧气张力相关。 在模拟氧化还原状态扰动的情况下，鉴定包括表位的疾病的标志物。 在先前未知的受体和活化配体的筛选在氧化还原状态改变的情况下进行。

公开(公告)号：US20080139669A1

公开(公告)日：2008-06-12

申请号：US11975136

申请日：2007-10-16

申请人： Jonathan S. Stamler

发明人： Jonathan S. Stamler

IPC分类号： A61K31/04 ,  A61P1/00

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

摘要： 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.

摘要翻译： 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。

公开(公告)号：US07259250B2

公开(公告)日：2007-08-21

申请号：US11052141

申请日：2005-02-08

申请人： Jonathan S. Stamler ,  Eric J. Toone

发明人： Jonathan S. Stamler ,  Eric J. Toone

IPC分类号： C07D211/90 ,  C07D405/14 ,  C07D413/04 ,  C07D231/12 ,  A61P29/00

CPC分类号： C07C245/04 ,  A61K31/00 ,  A61K31/195 ,  A61K31/785 ,  A61L31/10 ,  A61L31/16 ,  A61L2300/114 ,  A61L2300/606 ,  C07C207/00 ,  C07C207/04 ,  C07C219/06 ,  A61K2300/00

摘要： A C-nitroso compound having a molecular weight ranging from 225 to 1,000 (from 225 to 600 for oral administration) on a monomeric basis wherein a nitroso group is attached to a tertiary carbon, which is obtained by nitrosylation of a carbon acid having a pKa less than about 25, is useful as an NO donor. When the compound is obtained from a carbon acid with a pKa less than about 10, it provides vascular relaxing effect when used at micromolar concentrations and this activity is potentiated by glutathione to be obtained at nanomolar concentrations. When the compound is obtained from a carbon acid with a pKa ranging from about 15 to about 20, vascular relaxing effect is obtained at nanomolar concentrations without glutathione. In another embodiment, a biocompatible polymer incorporates a C-nitroso moiety.

摘要翻译： 一种分子量范围为225〜1000（口服给药时为225〜600）的C-亚硝基化合物，其中亚硝基连接到叔碳上，其通过具有pKa的碳酸的亚硝化而得到 小于约25，可用作NO供体。 当化合物从pKa小于约10的碳酸获得时，当以微摩尔浓度使用时，其提供血管松弛效果，并且该活性由以纳摩尔浓度获得的谷胱甘肽加强。 当化合物由pKa为约15至约20的碳酸获得时，在没有谷胱甘肽的纳摩尔浓度下获得血管松弛效果。 在另一个实施方案中，生物相容性聚合物包含C-亚硝基部分。