DESIGN OF MATERIAL FOR REMOVAL OF BLOOD TOXIC AGENTS

暴发性肝功能衰竭是一种罕见但严重的疾病。 主要由病毒性肝炎或醋氨酚过量引起。这个 紊乱的特征是严重的血浆蛋白失衡， 昏迷、排毒能力丧失和随后的蓄积 有毒新陈代谢产物。当治疗包括 传统的支持性治疗，患者的存活率只有10%到 20%这促使许多调查人员试图将 通过将血液灌流到不同的 吸着剂。尽管已经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 和相对较差的血液相容性。 在本申请中，我们打算解决这些缺点 以前的方法。我们计划准备一种血液相容的 具有选择性脱毒能力的聚合物膜 各种内源性和外源性毒素。我们计划完成 这是通过封装解毒关键的酶UDP来实现的 磷脂酰胆碱中的葡萄糖醛酸基转移酶及其辅因子。 碱基聚合囊泡。我们选择了聚合的囊泡 因为它们的稳定性相对于传统的 脂质体。然后这些囊泡将被困在可弯曲的 为水凝胶膜提供了一种方便 配置。我们打算对这些膜进行评估 根据它们将苯酚酶转化为 无毒产品苯基葡萄糖醛酸苷。该组织的活动 固定化的酶将与同等的酶进行比较。 游离酶的数量。此外，我们还将研究 通过测定结合酶膜的血液相容性 膜上沉积的血浆蛋白的种类和数量 并通过评估红细胞和血小板活性在治疗后 暴露在膜中。 这些研究应为编制 适用于治疗广泛性肺炎的固定化酶材料 各种全身中毒。

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.