罂粟碱明胶微球治疗脑血管痉挛的实验研究

目的 研制罂粟碱明胶微球，探索微球药物控释系统治疗脑血管痉挛的可行性。方法 采用改良的双相乳化冷凝聚合法制备明胶微球。并将其与盐酸罂粟碱复合。观察微球分散度、粒径及外观形态；计算微球包封率、载药率及体外释药特性。将自体动脉血分二次注入枕大池制备兔蛛网膜下腔出血（SAH）模型，随后将罂粟碱明胶微球注入该模型兔的枕大池；第7天时，观察并计算基底动脉血管横截面积。结果 微球大小均匀，平均直径（18．36±3．56）μm，载药量为28．0％，包封率为93-3％，体外14d内药物缓释91．0％。兔的基底动脉横截面积：正常组为（0．91±0．19）mm^2，SAH模型组为（0.3l±0．44）mm^2，明胶微球（不含罂粟碱）组为（0．21±0．05）mm^2，罂粟碱明胶微球组为（0．71±0．11）mm^2；罂粟碱明胶微球与SAH模型组和明胶微球组间有明显差异（P〈0．05）。结论 在蛛网膜下腔早期注入罂粟碱缓释明胶微球对实验性脑血管痉挛有防治作用。

Treatment of Cerebral Vasospasm Following Subarachnoid Hemorrhage by Papaverine-gelatin Microspheres in Rabbits

Objectives To prepare papavefine-gelatin microspheres and explore the feasibility for treating vasospasm following subarachnoid hemorrhage （SAH） by controlled releasing system of the microspheres. Methods Gelatin microspheres were prepared by improved biphasic emulsification and cold-condensation method and loaded with papavefine. The morphology of the microspheres was observed by election and light microscopes. The encapsulation rate, drug content and the drug release of the microspheres were tested and calculated. The papavefine -gelatin microspheres were injected into magna cistern of rabbits with vasospasm induced by injecting themselves artery blood into the magna cisterns in twice. The areas of transverse sections of the rabbit basilar arteries were determined 7 days after injection of themselves blood into the magna cisterns. Results The diameter of the microspheres was （18.36±3.56）μm. The encapsulation rate was 93.3%, and drug content was 28.0%. The total amount of the sustained-releasing drug within 14 days was 91.0%. The areas of transverse sections of basilar arteries in the treatment group with papavefine-gelatin microspheres, blank control group, control group treated with gelatin mierosphere without papavefine and normal group （without injection of the arterial blood and the microspheres） were （0.71μ0.11）mm^2, （0.31±0.44）mm^2, （0.21±0.05）mm^2 and （0.91±0.19）mm^2 respectively. There was significant difference in the areas of the transverse section of the basilar arteries between papaverine-gelatin microsphere group and blank control group, or and control group treated with gelatin microsphere without papaverine group （P〈0.05）. Conclusion It is suggested that papaverine-gelatin microspheres may be of good preventing and curative effect on the cerebral vasospasm after SAH.