POLYNITROXYL HEMOGLOBIN:NEUROPROTECTIVE OXYGEN CARRIER

聚硝基血红蛋白：神经保护性氧载体

• 批准号: 6298968
• 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: 2001-03-15 至 2001-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6298968
• 关键词: antiinflammatory agents; blood /plasma substitute; drug design /synthesis /production; hemoglobin; laboratory mouse; neuroprotectants; neurotoxicology; nitric oxide; oxidative stress; oxygen transport; pharmacokinetics

DESCRIPTION: (Investigator's abstract) Polynitroxyl hemoglobin (PNH) will be developed as a neuroprotective oxygen carrier. PNH is different from 1st generation hemoglobin-based oxygen carriers (HBOCs) in that it has added anti-inflammatory activity in addition to oxygen carrier function. PNH is created by covalently attached nitroxides, an analogue of nitric oxide (NO) in a piperdine "cage," to HBOC. We have shown that PNH is an oxygen carrier with anti-inflammatory superoxide dismutase and catalase mimetic activities. In the Phase I of the present application, we propose to develop PNH as an anti-inflammatory oxygen carrier and demonstrate that it is resistant to oxidative damage in vitro and neuroprotective in vivo. In Phase II of this SBIR application, we propose to elucidate the mechanisms and efficacy of PNH with a hemodilution protocol in clinically relevant brain injury models. In a companion Phase I/Il SBIR entitled "Polynitroxyl Hemoglobin (PNH) : Preclinical Safety," we propose to conduct toxicology studies of PNH for an IND submission to FDA. PROPOSED COMMERCIAL APPLICATION: An oxygen carrying resuscitative fluid with anit-inflammatory activities such as PNH is highly desirable. HBOC products in advanced clinical development, provide only oxygen delivery. Unfortunately, during severe hemorrhage, or trauma, there is significant inflammatory (ischemia and reperfusion) injury. The inflammatory injury often lead to multiple organ failure (MOF). Therefore the use of PNH is to provide better protection against MOF in trauma resuscitation and can be used as a neuroprotective oxygen carrier in ischemic, hemorrhagic and traumatic head injury. The market potential for a 2nd generation HBOC is established to be 3 billion/year.

描述：（研究者摘要）多硝酰血红蛋白（PNH）将 作为一种神经保护性的氧气载体。PNH不同于第一次 第二代血红蛋白氧载体（HBOCs），因为它添加了 除了氧载体功能之外，还具有抗炎活性。PNH是 由共价连接的氮氧化物产生，一氧化氮（NO）的类似物， 一个哌啶“笼”到HBOC。我们已经证明PNH是氧载体， 抗炎超氧化物歧化酶和过氧化氢酶模拟活性。在 在本申请的第一阶段，我们提出将PNH开发为 抗炎氧载体，并证明它是耐 体外氧化损伤和体内神经保护。在本SBIR的第二阶段 应用，我们建议阐明PNH的机制和疗效与 临床相关脑损伤模型中血液稀释方案。中 标题为“多硝酰血红蛋白（PNH）：临床前”的I/II期SBIR 安全性，”我们建议为IND提交进行PNH的毒理学研究 FDA。 拟定商业应用： 一种具有抗炎活性如PNH的携氧复苏液， 非常可取。 HBOC产品处于高级临床开发阶段，仅提供氧气 交付. 不幸的是，在严重出血或创伤期间， （缺血和再灌注）损伤。 炎症损伤常导致多器官功能衰竭 （财政部）。 因此，使用PNH是为了提供更好的保护，防止多器官功能衰竭的创伤 复苏，并可用作缺血性、出血性 和头部创伤 第二代HBOC的市场潜力已经确定， 30亿/年。