DESIGN OF MATERIAL FOR REMOVAL OF BLOOD TOXIC AGENTS

去除血液毒剂的材料设计

• 批准号: 3359694
• 负责人: Martin M. Klinger
• 金额: $ 9.49万
• 依托单位: SOUTHERN RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-01-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3359694
• 关键词: blood toxicology; detoxification; electrofocusing; gel; gel electrophoresis; glucuronosyltransferase; hemotoxin; histocompatibility; liposomes; liver failure; nuclear magnetic resonance spectroscopy; phosphatidylcholines; polymerization; thin layer chromatography

Fulminant hepatic failure is a rare but serious condition caused primarily by viral hepatitis or acetaminophen overdose. The disorder is characterized by severe plasma protein imbalance, coma, loss of detoxification ability and subsequent accumulation of toxic metabolic products. When treatment consists of conventional supportive therapy, patient survival is only 10 to 20%. This has prompted many investigators to attempt to remove the accumulated toxins by perfusing the blood over various sorbents. Although there have been some dramatic successes, sorbent hemoperfusion suffers from a marked lack of specificity and relatively poor hemocompatibility. In the present application we intend to address the disadvantages of the previous approaches. We plan to prepare a hemocompatible polymer membrane with the ability to selectively detoxify a wide range endogenous and exogenous toxins. We plan to accomplish this by encapsulating an enzyme central to detoxification, UDP glucuronyl transferase, and its cofactor in phosphatidylcholine- base polymerized vesicles. We have chosen polymerized vesicles because of their superior stability relative to conventional liposomes. These vesicles will then be trapped in flexible hydrogel membranes in order to provide a convenient configuration. We intend to evaluate these membranes on the basis of their ability to enzymatically convert phenol to the nontoxic product, phenylglucuronide. The activity of the immobilized enzymes will be compared to that of an equivalent quantity of the free enzyme. Furthermore, we will examine the hemocompatibility of the bound-enzyme membranes by determining the type and quantity of plasma protein deposited on the membrane and by estimating erythrocyte and platelet viability after exposure to the membrane. These studies should provide the basis for the preparation of immobilizedenzyme materials suitable for the treatment of a wide variety of systemic intoxications.

暴发性肝衰竭是一种罕见但严重的疾病 主要由病毒性肝炎或对乙酰氨基酚过量引起。 这 疾病的特点是严重的血浆蛋白失衡， 昏迷、解毒能力丧失及随后的蓄积 有毒代谢产物。 当治疗包括 传统的支持治疗，患者的生存期只有10到10年 20%。 这促使许多调查人员尝试删除 通过将血液灌注到各个部位而积累的毒素 吸附剂。 尽管取得了一些戏剧性的成功， 吸附剂血液灌流明显缺乏特异性 且血液相容性相对较差。 在本申请中，我们打算解决缺点 以前的方法。 我们计划准备一个血液相容剂 聚合物膜具有广泛的选择性解毒能力 内源性和外源性毒素的范围。 我们计划完成 这是通过封装一种解毒核心酶 UDP 来实现的 葡萄糖醛酸转移酶及其磷脂酰胆碱中的辅因子- 基础聚合囊泡。 我们选择了聚合囊泡 因为它们相对于传统的稳定性优越 脂质体。 然后这些囊泡将被困在柔性的 水凝胶膜，以提供方便 配置。 我们打算评估这些膜 其基础是能够将苯酚酶促转化为 无毒产品，苯基葡萄糖苷酸。 的活动 固定化酶将与同等酶进行比较 游离酶的量。 此外，我们将检查 通过测定结合酶膜的血液相容性 沉积在膜上的血浆蛋白的类型和数量 并通过评估红细胞和血小板活力后 暴露于膜。 这些研究应该为准备 固定化酶材料适用于多种疾病的治疗 各种全身中毒。