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：（研究者的摘要）聚硝酸血红蛋白（PNH）将是 发展为神经保护氧载体。 PNH与第一个不同 产生的血红蛋白基氧载体（HBOC）已增加 除氧载体功能外，抗炎活性。 PNH是 由共同附着的硝酸二氧化物，一氧化氮（NO）中的类似物创建 吹笛的“笼”，送给HBOC。我们已经证明PNH是一个氧气载体 抗炎超氧化物歧化酶和过氧化氢酶模拟活性。在 本应用程序的第一阶段，我们建议将PNH作为一个 抗炎氧载体，并证明它具有抗性 体外的体外和神经保护性损伤。在此SBIR的第二阶段 应用，我们建议阐明PNH的机制和功效 临床相关的脑损伤模型中的血液稀释方案。在 伴侣I/IL SBIR标题为“聚硝氧基血红蛋白（PNH）：临床前 安全，“我们建议对PNH进行毒理学研究以进行IND提交 到FDA。 拟议的商业应用： 带有抗炎活性（如PNH）的携带复苏液的氧气是 非常可取。 高级临床开发中的HBOC产品，仅提供氧气 送货。 不幸的是，在严重的出血或创伤期间，有明显的炎症 （缺血和再灌注）受伤。 炎症损伤通常会导致多器官衰竭 （MOF）。 因此，PNH的使用是在创伤中更好地保​​护MOF 复苏，可以用作缺血性，出血性的神经保护氧载体 和头部受伤。 建立了第二代HBOC的市场潜力 是30亿/年。