レシチン化SOD : 臨床応用可能なSOD製剤を目指して

概要

論文の詳細を見る
Superoxide dismutase (SOD), an enzyme that scavenges superoxide anion (O2-), has been suggested as a possible therapeutic tool, for treating diseases related to active oxygen spiecies. However, its low cell membrane affinity and rapid metabolic clearance limit its clinical application. We synthesized SOD, in which cytotropic phosphatidylcholine derivatives were covalently bound to recombinant human SOD, in order to target SOD to cell membrane. Lecithinized SOD was shown to have a high cell membrane affinity using laser confocal imaging technique, showed a longer plasma half-life, and efficiently scavenged O2- produced by phorbol myristate acetate(PMA). Lecithinized SOD showed more potent inhibitory effect on human endothelial cells injury by O2- produced by PMA stimulated neutrophils and on ischemia-reperfusion mouse paw edema than, that of unmodified SOD. Moreover, other potent pharmacological activities of lecithinized SOD has been reported, and toxicological and antigenic findings of lecithinized SOD had no particullar in comparison with unmodified SOD. Accordingly, lecithinized SOD seems to have the potential for clinical applications.
日本DDS学会の論文
1995-01-10