NITROXIDE THERAPY FOR INFLAMMATORY BOWEL DISEASE

炎症性肠病的氮氧化物疗法

• 批准号: 6311264
• 负责人: Carleton Hsia
• 金额: $ 10万
• 依托单位: SYNZYME TECHNOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2001-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6311264
• 关键词: antioxidants; biotechnology; colitis; drug administration rate /duration; drug administration routes; drug design /synthesis /production; drug screening /evaluation; female; histology; inflammatory bowel diseases; laboratory mouse; nitrogen oxides; oxidative stress; pharmacokinetics; pharmacology; superoxides; tissue /cell preparation

DESCRIPTION (Adapted from the application): Free radicals play important roles in inflammatory bowel disease (IBD), and the reduction or elimination of the adverse effects of these oxidants could provide novel therapies. Antioxidants have been reported to reduce tissue injury in colitis models, but more potent, stable and bioavailable antioxidant compounds are required. This project will test a new class ofantioxidants based on polynitroxylation technology, or linkage of nitroxides (stable N-oxyl radicals) to biological macromolecules. In a preliminary study, polynitroxyl-starch (PNS) acted synergistically with the free (unbound) nitroxide compound Tempol to reduce oxidants (especially superoxide) and attenuate inflammation in TNBS-induced murine colitis. We hypothesize that TNBS colitis involves significant superoxide-mediated injury, and that PNS and Tempol can attenuate this injury. Specific aims are: (1) Produce PNS and characterize its antioxidant activity. (2) Pharmacokinetically define optimal dose and route of administration. (3) Define efficacy in TNBS-induced mouse colitis. If this is successful, Phase II will define mechanisms of action in animal models of IBD (including the IL-10-/- knockout mouse which spontaneously develops colitis) and other studies required for progression to clinical testing in IBD. PROPOSED COMMERCIAL APPLICATION: Inflammatory bowel disease is a significant health problem. If successful this research will lead to the development of a novel therapeutic agent(s) for the treatment of IBD. This would represent a significant commercial opportunity and provide substantial benefit to patients.

描述（根据应用程序改编）：自由基发挥重要作用 在炎症性肠病（IBD）中，减少或消除 这些氧化剂的不良影响可以提供新颖的疗法。抗氧化剂 据报道，在结肠炎模型中减少组织损伤，但更有效， 需要稳定和生物利用的抗氧化剂化合物。这个项目将 测试基于多硝基化技术的新类抗氧化剂或 氮氧化物（稳定的N-氧基自由基）与生物大分子的联系。在 一项初步研究，多硝基酰亚胺淀粉（PNS）与 游离（未结合的）硝基化合物tempol以降低氧化剂（尤其是 超氧）并减弱了TNBS诱导的鼠结肠炎的炎症。我们 假设TNBS结肠炎涉及明显的超氧化物介导的损伤， PNS和Tempol可以减轻这种伤害。具体目的是：（1） 产生PN并表征其抗氧化活性。 （2）在药物上 定义最佳剂量和给药途径。 （3）定义功效 TNBS诱导的小鼠结肠炎。如果成功，第二阶段将定义 IBD动物模型中的作用机理（包括IL-10 - / - 敲除 自发发展结肠炎的小鼠和其他研究 IBD中的临床测试进展。 拟议的商业应用： 炎症性肠病是一个重大的健康问题。 如果成功的话，这项研究将 导致开发新型治疗剂以治疗IBD。 这会 代表了一个巨大的商业机会，并为患者带来了可观的好处。