醋酸地塞米松静注乳剂的抗炎活性及动物组织分布研究

Tissue distribution and anti-inflammatory activity of dexamethasone ac etate incorporated in lipid emulsion

目的 观察醋酸地塞米松静注乳剂的抗炎活性及在小鼠体内组织分布特征。方法 以大鼠角叉胶肉芽肿为抗炎模型进行药效学研究 ,用放射性同位素3H示踪法考察在小鼠体内组织分布特征。结果 与地塞米松磷酸钠水针剂相比 ,醋酸地塞米松静注乳剂样品在低剂量 (0 .0 5mg·kg- 1 )下与水针剂高剂量 (0 .3mg·kg- 1 )的抑制率相当 ;与日本产品相比 ,二者无显著差异 ;醋酸地塞米松静注乳剂在脾、肺、炎症组织内有较高分布 ,而地塞米松磷酸钠水针剂在肌肉组织具有较高浓度。结论 将醋酸地塞米松制备成乳剂能够改变其在动物组织内的分布 。

OBJECTIVE: To study the anti-inflammatory activity and distribution patterns in tissues of dexamethasone acetate emulsion. METHODS The anti-inflammatory activity of dexamethasone acetate emulsion, dexamethasone sodium phosphate and Japanese product given intravenously were evaluated by using the preformed carrageenan granuloma pouch method. RESULTS: The anti-inflammatory activity of dexamethasone acetate emulsion at the low dose of 0.05 mg&middotkg-1 was as potent as free dexamethasone at the high dose of 0.3 mg&middotkg-1. The distribution patterns in tissues of [3H] dexamethasone acetate given as lipid emulsion and [3H] dexamethasone phosphate given as aqueous solution in mice were markedly different. Dexamethasone acetate emulsion showed much higher concentrations in the liver, spleen, lung, and inflammed tissues respectively, whereas dexamethasone sodium phosphate had a high concentration in the muscles. These results indicated that dexamethasone incorporated in lipid emulsion were taken up by the reticuloendothelial system and inflammatory cells much more than the free dexamethasone. CONCLUSION: When dexamethasone acetate were incorporated into emulsion, its distribution patterns in tissues were changed and they had a stronger anti-inflammatory activity and may decrease its side-effects.