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1. 发明申请

US20070092512A1 Preventing bacterial or viral infectivity and composition containing infection preventing additive 失效
标题翻译：预防细菌或病毒感染性和含有感染预防添加剂的组合物
公开(公告)号：US20070092512A1
公开(公告)日：2007-04-26
申请号：US11544559
申请日：2006-10-10
申请人： Yehia Daaka , Jonathan Stamler
发明人： Yehia Daaka , Jonathan Stamler
IPC分类号： A61K39/395 , A61K31/65
CPC分类号： C07K16/2863 , A61K31/65 , A61K2039/505 , C07K2317/77
摘要： A nitric oxide synthesis inhibitor or nitric oxide scavenger is administered to prevent development of infection, to prevent development of a cancer where overstimulation of a receptor contributes to the cancer development, and to prevent loss of beta agonist responsivity and as a treatment in combination with a receptor blocker. Compositions include nitric oxide synthesis inhibitor or nitric oxide scavenger containing spermicidal compositions, nasal steroid compositions, urinary tract infection prophylaxis compositions, compositions for prophylaxis of EGFR associated cancer and human blood component(s) composition for transfusion.
摘要翻译：施用一氧化氮合成抑制剂或一氧化氮清除剂以防止感染的发展，以防止受体过度刺激导致癌症发展的癌症的发展，并且防止β激动剂反应性的丧失以及作为与受体阻断剂。组合物包括一氧化氮合成抑制剂或含有杀精组合物的一氧化氮清除剂，鼻型类固醇组合物，尿路感染预防组合物，用于预防EGFR相关癌症的组合物和用于输血的人血液成分组合物。

2. 发明申请

US20070066546A1 Compositions for the reversible thioesterification of signaling proteins and methods of using same 有权
标题翻译：信号蛋白的可逆硫酯化的组合物及其使用方法
公开(公告)号：US20070066546A1
公开(公告)日：2007-03-22
申请号：US11488992
申请日：2006-07-18
申请人： Jonathan Stamler , Jordan Gutterman
发明人： Jonathan Stamler , Jordan Gutterman
IPC分类号： A61K31/704 , C07H15/24 , C12Q1/26 , C12P33/00 , C12N5/08 , C12N1/21
CPC分类号： A61K47/48246 , A61K38/00 , A61K47/64 , A61K47/65 , C07H15/24 , C07K1/1077 , C07K1/1133 , G01N33/5011 , G01N33/5023 , G01N33/5041 , Y02A50/473
摘要： Avicins and other thioesterification agents are used to modify cysteine groups of signaling proteins in order to modify their activity. Pathologies associated with signaling proteins which are regulatable through this method are treated using these thioesterification agents. These pathologies include those involving proteins which modulate physiologic redox status of organisms including arthersclerosis, cancer, bacterial infection, inflammation, and neurological disorders.
摘要翻译： Avicins和其他硫酯化试剂用于修饰信号蛋白的半胱氨酸基团以改变其活性。使用这些硫酯化试剂处理通过该方法可调节的与信号蛋白相关的病理学。这些病理学包括涉及调节生物体的生理氧化还原状态的蛋白质，包括硬脑膜炎，癌症，细菌感染，炎症和神经障碍。

3. 发明申请

US20060198831A1 Nitrosylation of protein SH groups and amino acid residues as a therapeutic modality 审中-公开
公开(公告)号：US20060198831A1
公开(公告)日：2006-09-07
申请号：US11418367
申请日：2006-05-05
申请人： Jonathan Stamler , Joseph Loscalzo , Daniel Simon , David Singel
发明人： Jonathan Stamler , Joseph Loscalzo , Daniel Simon , David Singel
IPC分类号： A61K38/43 , A61K38/38 , A61K38/17 , C12N9/00 , C07K14/775 , C07K14/765
CPC分类号： C12N9/6472 , A61K38/00 , C07K1/1077 , C07K14/3153 , C07K14/4702 , C07K14/76 , C07K14/765 , C07K14/805 , C07K16/00 , C12N9/6459 , C12Y304/21069
摘要： Nitrosylation of proteins and amino acid groups enables selective regulation of protein function, and also endows the proteins and amino acids with additional smooth muscle relaxant and platelet inhibitory capabilities. Thus, the invention relates to novel compounds achieved by nitrosylation of protein thiols. Such compounds include: S-nitroso-t-PA, S-nitroso-cathepsin; S-nitroso-lipoprotein; and S-nitroso-immunoglobulin. The invention also relates to therapeutic use of S-nitroso-protein compounds for regulating protein function, cellular metabolism and effecting vasodilation, platelet inhibition, relaxation of non-vascular smooth muscle, and increasing blood oxygen transport by hemoglobin and myoglobin. The compounds are also used to deliver nitric oxide in its most bioactive form in order to achieve the effects described above, or for in vitro nitrosylation of molecules present in the body. The invention also relates to the nitrosylation of oxygen, carbon and nitrogen moieties present on proteins and amino acids, and the use thereof to achieve the above physiological effects.

4. 发明申请

US20060194820A1 Reactive oxygen generating enzyme inhibitor with nitric oxide bioactivity and uses thereof 有权
公开(公告)号：US20060194820A1
公开(公告)日：2006-08-31
申请号：US11430986
申请日：2006-05-10
申请人： Jonathan Stamler , Eric Toone , Joshua Hare
发明人： Jonathan Stamler , Eric Toone , Joshua Hare
IPC分类号： A61K31/519 , C07D487/02
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.

5. 发明申请

US20060100159A1 Preventing desensitization of receptors 审中-公开
公开(公告)号：US20060100159A1
公开(公告)日：2006-05-11
申请号：US11274047
申请日：2005-11-15
申请人： Jonathan Stamler , Robert Lefkowitz , Erin Whalen , Walter Koch , Claude Plantadosi
发明人： Jonathan Stamler , Robert Lefkowitz , Erin Whalen , Walter Koch , Claude Plantadosi
IPC分类号： A61K38/05
CPC分类号： A61K31/21 , A61K31/19 , A61K31/223 , A61K31/5377 , A61K38/063
摘要： Desensitization of receptors that control disease is prevented by inhibiting G-protein receptor kinases. This has applicability, e.g., for patients with heart failure or on a left ventricular heart device or a heart pump after surgery or about to undergo surgery and at high risk for a cardiac event or on an opiate or addicted to opiate or with cystic fibrosis or rheumatoid arthritis.

6. 发明申请

US20050203295A1 C-nitroso compounds and use thereof 失效
标题翻译： C-亚硝基化合物及其用途
公开(公告)号：US20050203295A1
公开(公告)日：2005-09-15
申请号：US11052777
申请日：2005-02-09
申请人： Jonathan Stamler , Eric Toone
发明人： Jonathan Stamler , Eric Toone
IPC分类号： A61K31/00 , A61K31/194 , A61K31/195 , A61K31/222 , A61K31/553 , A61K31/635 , A61K38/00 , A61L27/00 , A61L31/00 , A61P7/02 , A61P9/10 , A61P29/00 , A61P31/04 , A61P31/12 , C07C207/00 , C07C291/08 , C07D231/12 , C07D267/04 , C07D279/02 , C07D267/02
CPC分类号： C07C207/00 , A61K31/00 , A61K31/195 , A61K2300/00
摘要： A C-nitroso compound having a molecular weight ranging from about 225 to about 1,000 (from about 225 to about 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. The compound is preferably water-soluble and preferably contains a carbon alpha to the nitrosylated carbon which is part of a ketone group. In one embodiment, the C-nitroso compound is obtained by nitrosylation of a conventional drug or such drug modified to modify the carbon acid pKa thereof When such drug is a nonsteroidal anti-inflammatory drug, the resulting C-nitroso compound functions as a COX-1 and COX-2 inhibitor without the deleterious effects associated with COX-1 inhibition but with the advantageous effects associated with COX-1 and COX-2 inhibition. One such C-nitroso compound is a nitrosoketoibuprofen. A specific example of this kind of compound is isolated as dimeric 2-[4′-(α-nitroso)isobutyrylphenyl]propionic acid. In another case, the C-nitroso compound contains the moiety where X is S, O or NR. One embodiment is directed to COX-2 inhibitors where a tertiary carbon atom and/or an oxygen atom and/or a sulfur atom is nitrosylated.
摘要翻译：单体基团的分子量范围为约225至约1,000（约225至约600）的C-亚硝基化合物，其中亚硝基连接到叔碳上，其通过碳的亚硝基化获得 pKa小于约25的酸可用作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。该化合物优选是水溶性的并且优选地含有作为酮基的一部分的亚硝基化碳的碳α。在一个实施方案中，C-亚硝基化合物通过常规药物的亚硝基化或经修饰以改变其碳酸pKα的药物而获得。当这种药物是非甾体抗炎药物时，所得的C-亚硝基化合物起COX- 1和COX-2抑制剂，没有与COX-1抑制相关的有害作用，但具有与COX-1和COX-2抑制相关的有利效果。一种这样的C-亚硝基化合物是亚硝基基布洛芬。这种化合物的具体实例被分离为二聚2- [4' - （α-亚硝基）异丁酰苯基]丙酸。在另一种情况下，C-亚硝基化合物包含其中X是S，O或NR的部分。一个实施方案涉及其中叔碳原子和/或氧原子和/或硫原子被亚硝酰化的COX-2抑制剂。

7. 发明申请

US20050148612A1 Reversing, postponing or preventing the occurrence of GTN tolerance and/or generation of reactive oxygen species from mitochondria 失效
标题翻译：逆转，推迟或预防GTN耐受和/或从线粒体产生活性氧的发生
公开(公告)号：US20050148612A1
公开(公告)日：2005-07-07
申请号：US10980801
申请日：2004-11-04
申请人： Jonathan Stamler , Zhiqiang Chen , Thomas Munzel
发明人： Jonathan Stamler , Zhiqiang Chen , Thomas Munzel
IPC分类号： A61K31/04 , A61K31/21 , A61K31/41 , A61K31/513 , A61K31/52
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。

8. 发明授权

US5574068A S-nitrosothiols as smooth muscle relaxants and therapeutic uses thereof 失效
标题翻译： S-亚硝基硫醇作为平滑肌松弛剂及其治疗用途
公开(公告)号：US5574068A
公开(公告)日：1996-11-12
申请号：US338893
申请日：1994-11-14
申请人： Jonathan Stamler , Joeseph Loscalzo , Adam Slivka , Daniel Simon , Robert Brown , Jeffrey Drazen
发明人： Jonathan Stamler , Joeseph Loscalzo , Adam Slivka , Daniel Simon , Robert Brown , Jeffrey Drazen
IPC分类号： A61K38/00 , C07C381/00 , C07K5/02 , A61K31/195
CPC分类号： C07C381/00 , C07K5/0215 , A61K38/00
摘要： S-nitrosothiols exert a potent relaxant effect, mediated both by guanylate cyclase, and a cGMP-independent mechanism, upon non-vascular smooth muscle. Such types of smooth muscle include airway, gastrointestinal, bladder, uterine and corpus cavernosal. Thus, S-nitrosothiols may be used for the treatment or prevention of disorders associated with relation of smooth muscle, such as airway obstruction, and other respiratory disorders, bladder dysfunction, premature labor and impotence. Additionally, S-nitrosothiols may be used to alleviate smooth muscle contraction and spasm, and thus facilitate procedures involving diagnostic instrumentation, such as endoscopy, bronchoscopy, laparoscopy and cystoscopy. S-nitrosothiols also increase the binding affinity between hemoglobin and oxygen, and therefore, may be used to improve hemoglobin-oxygen binding, and oxygen transport to bodily tissues.
摘要翻译：在非血管平滑肌上，S-亚硝基硫醇发挥强效的松弛作用，由鸟苷酸环化酶和cGMP非依赖性机制介导。平滑肌的这种类型包括气道，胃肠道，膀胱，子宫和海绵体。因此，S-亚硝基硫醇可用于治疗或预防与平滑肌（例如气道阻塞）和其它呼吸系统疾病，膀胱功能障碍，早产和阳with有关的疾病。此外，S-亚硝基硫醇可用于缓解平滑肌收缩和痉挛，从而促进涉及诊断仪器的手术，如内窥镜检查，支气管镜检查，腹腔镜检查和膀胱镜检查。 S-亚硝基硫醇还增加血红蛋白和氧之间的结合亲和力，因此可用于改善血红蛋白 - 氧结合，以及氧输送到身体组织。

9. 发明授权

US09770500B2 S-nitrosylation of glucosylating toxins and uses therefor 有权
公开(公告)号：US09770500B2
公开(公告)日：2017-09-26
申请号：US13485801
申请日：2012-05-31
申请人： Tor C. Savidge , Jonathan Stamler
发明人： Tor C. Savidge , Jonathan Stamler
IPC分类号： A61K31/6615 , A61K39/08 , A61K45/06 , A61K31/198 , A61K31/21 , A61K38/06
CPC分类号： A61K39/08 , A61K31/198 , A61K31/21 , A61K31/6615 , A61K38/063 , A61K45/06 , Y02A50/469 , A61K2300/00
摘要： Provided herein are methods for ameliorating the pathophysiology cysteine protease exotoxin comprising the step of administering to said individual an effective dose of an S-nitrosylating agent and an inositol phosphate or analog thereof.

10. 发明申请

US20070191478A1 Methods of treating cardio pulmonary diseases with NO group compounds 审中-公开
标题翻译：用NO组化合物治疗心肺疾病的方法
公开(公告)号：US20070191478A1
公开(公告)日：2007-08-16
申请号：US11231162
申请日：2005-09-20
申请人： Jonathan Stamler , Eric Toone , Andrew Gow
发明人： Jonathan Stamler , Eric Toone , Andrew Gow
IPC分类号： A61K31/21
CPC分类号： C12N5/0641 , A61K31/197 , A61K31/21 , A61K33/00 , A61K33/04 , A61M2202/0275 , A61K2300/00
摘要： Treatment of pulmonary disorders associated with hypoxemia and/or smooth muscle constriction and/or inflammation comprises administering into the lungs as a gas a compound with an NO group which does not form NO2/NOx in the presence of oxygen or reactive oxygen species at body temperature. Treatment of cardiac and blood disorders, e.g., angina, myocardial infarction, heart failure, hypertension, sickle cell disease and clotting disorders, comprises administering into the lungs as a gas, a compound which reacts with cysteine in hemoglobin and/or dissolves in blood and has an NO group which is bound in said compound so that it does not form NO2/NOx in the presence of oxygen or reactive oxygen species at body temperature. Exemplary of the compound administered in each case is ethyl nitrite. Treatment of patient in need of improved oxygenation, blood flow of and/or thinning of blood comprises providing in the patient a therapeutic amount of red blood cells loaded with nitrosylated hemoglobin. A method is directed to screening drugs that increase level of nitrosoglutathione in airway lining fluid.
摘要翻译：与低氧血症和/或平滑肌收缩和/或炎症相关的肺部疾病的治疗包括以肺部作为气体给予具有不形成NO 2的NO组的化合物在体温存在氧或活性氧的情况下。治疗心脏和血液疾病，例如心绞痛，心肌梗死，心力衰竭，高血压，镰状细胞病和凝血障碍，包括作为气体给予肺，与血红蛋白中的半胱氨酸反应和/或溶解于血液中的化合物和具有在所述化合物中结合的NO基团，使得其在体温存在氧或活性氧的情况下不形成NO 2 / NO x 2 x。在每种情况下施用的化合物的实例是亚硝酸乙酯。治疗需要改善氧合，血流和/或血液变薄的患者包括在患者体内提供加载有亚硝基化血红蛋白的治疗量的红细胞。一种方法是用于筛选增加气道衬里液中亚硝基谷胱甘肽水平的药物。

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