醋酸地塞米松静注乳剂的制备及性质研究

Studies on preparation and properties of intravenous dexamethasone acetate emulsion

目的 研究醋酸地塞米松静注乳剂的处方及制备工艺 ,并对其性质进行考察。方法 以国产注射用大豆磷脂、泊洛沙姆 (poloxamer)为复合乳化剂 ,加入适量的稳定剂及助表面活性剂 ,用正交设计筛选出较优的处方及工艺 ,并经过中试放大制备出醋酸地塞米松静注乳剂。结果 制备的乳剂符合中国药典 2 0 0 0年版对静注乳剂的要求 ,与日本产品相比 ,粒度分布无明显差异 ,30℃下考察 6个月 ,物理及化学性质稳定。结论 筛选出的处方工艺经中试放大制备的静注乳剂性质稳定 。

Objective: To study the anti-inflammatory activity and tissue distribution patterns of intravenous emulsion of dexamethasone acetate in mice. Methods: The anti-inflammatory solution for injection and Limethasone(Jepanese product) given intravenously were evaluated by using the preformed carrageenan granuloma pouch method in rats. Results: The anti-inflammatory activity of dexamethasone acetate emulsion at low dose of 0.05 mg·kg^(-1) was as potent as dexamethasone sodium phosphate solution at high dose of 0.3 mg·kg^(-1). The distribution patterns in mice tissues of [3H]dexamethasone acetate emulsion and [3H]dexamethasone sodium phosphate solution in mice were markedly different. Dexamethasone acetate emulsion showed a much higher concentration in the liver, spleen, lung, and inflamed tissues, whereas dexamethasone sodium phosphate had a high concentration in the muscles of vastus lateralis. These results may indicate that dexamethasone incoporated in lipid emulsion was taken up by the reticuloendothelial system and inflammatory cells much more than dexamethasone sodium phosphate solution. Conclusion: When dexamethasone acetate was incorporated in emulsion, the distribution patterns in tissues were changed and they had a stronger anti-inflammatory activity.