碘醚柳胺脂质体定向剂防治牛羊肝片吸虫病研究 Ⅰ.碘醚柳胺脂质体定向剂的制备

THE PROPHYLAXIS AND TREATMENT OF FASCIOLIASIS IN CATTLEAND SHEEP WITH RAFOXANIDE LIPOSOMES . THE PREPARATION OF RAFOXANIDE LIPOSOMES

用改良的冷冻融溶法制备出碘醚柳胺（Ｒａｆｏｘａｎｉｄｅ，Ｒａｆ）脂质体定向剂，并对其药物特性进行了观察与测定。用Ｒａｆ与聚乙烯吡咯烷酮（Ｐｏｌｙｖｉｎｙｌｐｙｒｏｌｉｄｏｎｅ，ＰＶＰ）共沉法解决了Ｒａｆ在水性介质中不溶的问题，从而为制备该药脂质体创造了必要条件。采用单因素比较法优选出制备碘醚柳胺脂质体的最佳处方组成：药脂比为１∶２７（ｗ／ｗ）；Ｐｃ与Ｃｈｏｌ比为２∶１（ｍｏｌ／ｍｏｌ）。结果显示，用此法制备的脂质体包封率可高达５８％；电镜下显示以多层脂质体为主，粒径大者４μｍ～６μｍ，小者０．１μｍ～１．０μｍ，后者约占６０％。在室温条件下贮存７５ｄ后，其包封率由原来的５６．９７％下降到５１．８３％，表明用本法制备的脂质体具有良好稳定性。

Rafoxanide(Raf) liposomes were prepared by modified freezethawing method. To improve solubility of Raf, Raf was made into Rafpolyvinylpyrrolidone(PVP) coprecipitate. Through singlefactor comparison, the optimal prescription selected was 127(w/w) for druglipid and 21(molmol) for lecithincholesterol. Under these conditions, the encapsulated rate of Rafliposomes was up to 58%. The size of Rafliposomes was observed and measured under electron microscope. The results indicated that most of vesicles were multilamellar and the size ranged from 0.1-6.0 m. To determine the stability, Rafliposomes were stored in room temperature for 75 days. The results showed that the encapsulated rate dropped from 56.97% to 51.83%, which indicated that Rafliposomes had a better stability.