聚乳酸的直接合成及其红霉素肺靶向药物微球的应用

STUDIES ON THE DIRECT SYNTHESIS OF POLYLACTIC ACID AND ITS APPLICATION IN ERYTHROMYCIN-POLY(DL-LACTIC ACID) MICROSPHERES FOR LUNG TARGETING

以DL-乳酸为原料,通过熔融聚合法直接合成外消旋聚乳酸(PDLLA)。以SnCl2为催化剂,用量0.5%(质量),在170℃、70Pa下反应10h,获得了粘均分子量为4100的PDLLA,将其应用于红霉素肺靶向微球的载体。用正交试验确定了红霉素-聚乳酸微球(ERY-PDLLA-MS)最佳成型工艺条件,用DSC和SEM表征其成球性能。微球体外缓释半衰期为28h,175h后累积释药百分率约为80%。注射微球混悬剂的兔肺组织中药物含量为普通市售红霉素注射剂的6倍,达到了肺靶向的目的。

Staring from D,Llactic acid, poly(DLlactic acid) (PDLLA) was directly synthesized through melt polycondensation. Catalyzed by SnCl2 (0.5 mass%) under 170 ℃ and 70 Pa, PDLLA with viscosityaverage molecular weight 4100 was produced, which was applied in erythromycinpoly(D,Llactic acid) microsphere (ERYPDLLAMS) for lung targeting. The optimal conditions for the preparation of ERYPDLLAMS were determined with orthogonal test. The ERYPDLLAMS was characterized with DSC and SEM. The halftime of release in vitro was 28h, after 175 h its accumulated release percent arrived 80%. The experiment with rabbits proved that, the drug content in lung tissue injected in the form of suspending ERYPDLLAMS mixture was 6 times as much as that injected with common injection, and ERYPDLLAMS could meet for lung targeting.