DESIGN OF MATERIAL FOR REMOVAL OF BLOOD TOXIC AGENTS

去除血液毒剂的材料设计

• 批准号: 3359693
• 负责人: DENNIS J MC CARTHY
• 金额: $ 10万
• 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 1991-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3359693
• 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， 主要是因为病毒性肝炎或扑热息痛过量 的 病症的特征在于严重的血浆蛋白失衡， 昏迷、丧失解毒能力和随后的积累 有毒的代谢产物。 当治疗包括 传统的支持疗法，病人的生存率只有10至 百分之二十 这促使许多调查人员试图删除 通过将血液灌注到各种 吸附剂。 虽然取得了一些巨大的成功， 吸附剂血液灌流明显缺乏特异性， 血液相容性较差。 在本申请中，我们打算解决以下缺点： 以前的方法。 我们计划准备血液相容性 聚合物膜具有选择性解毒的能力， 包括内源性和外源性毒素。 我们计划完成 这是通过封装一种对解毒至关重要的酶，UDP 葡萄糖醛酸基转移酶及其在磷脂酰胆碱中的辅因子， 碱基聚合的囊泡。 我们选择了聚合囊泡 由于它们相对于常规的、具有上级稳定性的 脂质体。 这些囊泡将被困在柔韧的 水凝胶膜以提供方便的 配置. 我们打算评估这些膜上 它们能够将苯酚酶促转化为 无毒产品，苯基葡萄糖醛酸苷。 的活性 将固定化酶与等同物的酶进行比较 游离酶的量。 此外，我们将研究 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的活力， 暴露在膜上。 这些研究报告应作为编写 固定化酶材料适用于治疗广泛的 各种系统性中毒