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    Method of using pyruvate and/or its derivatives for the treatment of cytokine-mediated inflammatory conditions
    2.
    发明申请
    Method of using pyruvate and/or its derivatives for the treatment of cytokine-mediated inflammatory conditions 审中-公开
    使用丙酮酸和/或其衍生物治疗细胞因子介导的炎性病症的方法

    公开(公告)号：US20050245609A1

    公开(公告)日：2005-11-03

    申请号：US11095031

    申请日：2005-03-31

    申请人： Mitchell Fink ,  Luis Ulloa ,  Kevin Tracey ,  Russell Delude

    发明人： Mitchell Fink ,  Luis Ulloa ,  Kevin Tracey ,  Russell Delude

    IPC分类号： A61K47/02 ,  A61K31/16 ,  A61K31/19 ,  A61K31/22 ,  A61P1/04 ,  A61P7/00 ,  A61P11/06 ,  A61P17/00 ,  A61P17/06 ,  A61P19/02 ,  A61P29/00

    CPC分类号： A61K31/22 ,  Y02A50/411

    摘要： This invention is directed to a method of using a therapeutic composition comprising an ester of an alpha-ketoalkanoic acid for the treatment of cytokine-mediated inflammatory conditions. The cytokine-mediated inflammatory conditions are mediated by, for example, Tumor Necrosis Factor (TNF), interleukin-1β (IL-1β)) or High Mobility Group B-1 (HMGB-1) mediator of inflammation. Exemplary cytokine-mediated inflammatory conditions include, but are not limited to, rheumatoid spondylitis, osteoarthritis, gouty arthritis, endotoxic shock, cerebral malaria, silicosis, pulmonary sarcoidosis, bone resorption disease, graft versus host disease, allograft rejections, fever and myalgia due to infection, AIDS related complex (ARC), Crohn's disease, rheumatoid arthritis, cachexia and septic shock.

    摘要翻译： 本发明涉及使用包含α-酮链烷酸酯的治疗组合物用于治疗细胞因子介导的炎性病症的方法。 细胞因子介导的炎性病症由例如肿瘤坏死因子（TNF），白细胞介素-1β（IL-1β））或高迁移率组B-1（HMGB-1）炎症介质介导。 示例性细胞因子介导的炎性病症包括但不限于类风湿性脊椎炎，骨关节炎，痛风性关节炎，内毒素性休克，脑疟疾，矽肺，肺结节病，骨吸收疾病，移植物抗宿主病，同种异体移植排斥，发热和肌肉酸痛 感染，AIDS相关复合物（ARC），克罗恩病，类风湿关节炎，恶病质和败血性休克。

    Two-part drug discovery system
    4.
    发明申请
    Two-part drug discovery system 审中-公开
    两部分药物发现系统

    公开(公告)号：US20050154536A1

    公开(公告)日：2005-07-14

    申请号：US10925862

    申请日：2004-08-25

    申请人： Carson Chow ,  Yoram Vodovotz ,  Gilles Clermont ,  Mitchell Fink ,  John Bartels ,  Steven Chang

    发明人： Carson Chow ,  Yoram Vodovotz ,  Gilles Clermont ,  Mitchell Fink ,  John Bartels ,  Steven Chang

    IPC分类号： A61B20060101 ,  G01N33/48 ,  G01N33/50 ,  G06F19/00

    CPC分类号： G01N33/5091 ,  G16B5/00 ,  G16C20/30

    摘要： A mathematical prognostic in which changes in a number of physiologically significant factors are measured and interpolated to determine a “damage fluction” incident to bacterial infection or other serious inflammation, followed by either or both of in vitro or in vivo investigations of a particular active agent (drug) and adjustment of the model so as better to evaluate the particular active agent. By measuring a large number of physiologically significant factors including, but not limited to, Interleukin 6 (IL-6), Interleukin 10 (IL-10), Nitric Oxide (NO), and others, it is possible to predict life versus death by the damage function, dD/dt. To evaluate one or more drug candidates against inflammation, the mathematical model is applied first, followed by in vivo and/or in vitro investigations, and the in vivo and/or in vitro investigations are in turn used to adjust or to enhance, if applicable, the mathematical model as it is applied to the particular drug candidate.

    摘要翻译： 一种数学预测，其中测量和内插多个生理学重要因素的变化以确定对细菌感染或其他严重炎症的“损伤流感”事件，随后是特定活性剂的体外或体内研究中的任一个或两者 （药物）和模型的调整，以便更好地评估特定的活性剂。 通过测量大量的生理学显着因子，包括但不限于白细胞介素6（IL-6），白细胞介素10（IL-10），一氧化氮（NO）等），可以预测寿命与死亡 损伤函数dD / dt。 为了评估一种或多种抗炎症候选药物，首先应用数学模型，然后进行体内和/或体外研究，并且如果适用，体内和/或体外研究又被用于调节或增强 ，它被应用于特定药物候选人的数学模型。

    Pyruvate ester composition and method of use for resuscitation after events of ischemia and reperfusion
    5.
    发明申请
    Pyruvate ester composition and method of use for resuscitation after events of ischemia and reperfusion 审中-公开
    丙酮酸酯组合物和缺血再灌注事件后复苏的方法

    公开(公告)号：US20050059738A1

    公开(公告)日：2005-03-17

    申请号：US10948026

    申请日：2004-09-23

    申请人： Alfred Ajami ,  Carrie Sims ,  Mitchell Fink

    发明人： Alfred Ajami ,  Carrie Sims ,  Mitchell Fink

    IPC分类号： A61K31/22 ,  A61K31/235 ,  A61K33/00 ,  A61K33/06

    CPC分类号： A61K31/235 ,  A61K31/22 ,  A61K33/00 ,  A61K2300/00

    摘要： A therapeutic composition comprising an alkyl, aralkyl, alkoxyalkyl or carboxyalkyl ester of 2ketoalkanoic acid and a component for inducing and stabilizing the enol resonance form of the ester at physiological pH values is disclosed. The composition of the invention further comprises a pharmaceutically acceptable carier vehicle in which the enol resonance form of the ester is stabilized at physiological pH values. Formulations containing the compositions of the invention permit the successful use of 2-ketoalkanoic acid esters, e.g., pyruvic acid esters, to treat, e.g., is chemic events, shock, organ reanimation, resuscitation and other recognized pyruvate-effective treatments. The compositions of the inventions are also useful in a process for preserving organ parts, organs or limbs removed from a living mammal and in need of preservation, e.g., for later transplantation to an organ recipient.

    摘要翻译： 公开了一种治疗组合物，其包含2-酮链烷酸的烷基，芳烷基，烷氧基烷基或羧烷基酯，以及用于在生理pH值下诱导和稳定酯的烯醇共振形式的组分。 本发明的组合物还包含药学上可接受的载体，其中酯的烯醇共振形式在生理pH值下稳定。 含有本发明组合物的制剂允许成功地使用2-酮链烷酸酯，例如丙酮酸酯，以治疗例如化学事件，休克，器官恢复，复苏和其他公认的丙酮酸有效治疗。 本发明的组合物还可用于保存从活的哺乳动物中除去并需要保存的器官部分，器官或四肢的方法，例如用于随后移植至器官接收者。

    Extracellular NAD+ and cADPR as potent anti-inflammatory agents
    7.
    发明申请
    Extracellular NAD+ and cADPR as potent anti-inflammatory agents 失效
    胞外NAD +和cADPR作为有效的抗炎剂

    公开(公告)号：US20050065109A1

    公开(公告)日：2005-03-24

    申请号：US10659063

    申请日：2003-09-10

    申请人： Mitchell Fink ,  Russell Delude ,  Xianonan Han

    发明人： Mitchell Fink ,  Russell Delude ,  Xianonan Han

    IPC分类号： A61K31/7076

    CPC分类号： A61K31/7076 ,  Y10S514/886 ,  Y10S514/921

    摘要： A method of prophylaxis or treatment of inflammatory conditions, including, but not limited to, intestinal epithelial inflammation due to intestine-specific conditions (e.g., Crohn's disease or ulcerative colitis) or systemic causes of inflammation (e.g., endotoxemia, sepsis, hemorrhagic shock/resuscitation or pancreatitis) is disclosed. In the method of the invention, an affected patient is administered a therapeutically effective amount of a composition including an NAD-related compound, in a form that is accessible to a receptor molecule, conveyed in a pharmaceutically acceptable carrier vehicle. NAD-related compounds include nicotinamide adenine dinucleotide (NAD+), cyclic adenosine diphosphate ribose (cADPR), or functionally equivalent analogues, derivatives, metabolites or agonists thereof or prodrugs therefor. Also disclosed are ex vivo and in vivo assay methods to test candidate compounds for activity, kits for carrying out the therapeutic methods or the assay methods of the invention and articles of manufacture that include compositions for use in the methods of the invention and instructions for the use thereof.

    摘要翻译： 包括但不限于由肠特异性病症引起的肠上皮炎症（例如克罗恩病或溃疡性结肠炎）或全身性炎症原因（例如，内毒素血症，败血症，出血性休克/ 复苏或胰腺炎）。 在本发明的方法中，给受影响的患者施用治疗有效量的包含NAD-相关化合物的组合物，其以在药学上可接受的载体载体中转运的受体分子可接近的形式。 NAD相关化合物包括烟酰胺腺嘌呤二核苷酸（NAD +），环状腺苷二磷酸核糖（cADPR）或功能等同的类似物，衍生物，代谢物或其激动剂或其前体药物。 还公开了用于测试候选化合物活性的离体和体内测定方法，用于实施本发明的治疗方法或测定方法的试剂盒和制品，其包括用于本发明方法的组合物和用于本发明方法的说明书 使用它。