羟基喜树碱脂肪乳的制备及其在人血浆中稳定性考察  

Preparation and stability of hydroxycamptothecin lipid emulsion

作　　者：董隽[1] 郭建新[1] 平其能[1] 

机构地区：[1]中国药科大学药剂教研室,南京210009

出　　处：《中国新药杂志》2005年第6期720-723,共4页Chinese Journal of New Drugs

摘　　要：目的:制备羟基喜树碱(HCPT)静脉注射脂肪乳,研究其在人血浆中对内酯型药物的保护作用。方法:采用乳化均质法,以注射级大豆油为油相,大豆卵磷脂为乳化剂制备O/W型的HCPT脂肪乳;测定乳剂的粒径和Zeta电位,考察含药脂肪乳的稳定性。通过体外血浆实验研究脂肪乳和注射液中的药物在人血浆中的稳定性。结果:HCPT静脉注射脂肪乳的物理稳定性良好,含量为(78.6±1.1)mg·L^(-1),平均粒径为(161.7±2.4)nm,Zeta电位为(-42.4±1.1)mV,115℃高压灭菌30min脂肪乳性状维持良好。与普通HCPT注射液相比,4h内脂肪乳可以显著降低血浆中药物内酯型向羧酸盐型的转化速率。结论:HCPT静脉注射脂肪乳剂可以显著提高血浆中内酯型药物的比例,从而提高药物的抗癌活性。Objective: To evaluate the stability of the serum hydroxycamptothecin (HCPT) with a lactone fragment in the lipid emulsion for intravenous injection. Methods: A HCPT lipid O/W emulsion was prepared by using a high-pressure homogenization, whose oily phase was soybean oil and emulsifier was soya lecithin. The stability of the lipid emulsion was assessed based on the emulsion droplet size, zeta potential and the amount of serum HCPT with the lactone fragment. Results: HCPT was incorporated into the lipid emulsion by (78.6±1.1)mg·L^(-1). The mean droplet size and zeta potential of the emulsion were (161.7±2.4) nm and (-42.4±1.1) mV, respectively. No deterioration in the emulsion stability was found when the emulsion was sterilized at 115℃ for 30 minutes. Compared with a commercial HCPT for injection, this lipid emulsion significantly decreased the transformation of serum HCPT structure, i. e., the conversion of lactone to carboxylate. Conclusion: This lipid emulsion provides a higher proportion of the serum HCPT with the lactone fragment, improving HCPT activities against carcinomas.

关 键 词：羟基喜树碱 脂肪乳 内酯型 羧酸盐型 

分 类 号：R944.9[医药卫生—药剂学] R979.1[医药卫生—药学]