【作者】 张雪梅；

【导师】 王晶； 潘卫三； 林东海； 刘珂；

【作者基本信息】 沈阳药科大学 ， 药物制剂， 2004， 硕士

【摘要】 本文研究了人参皂苷C-K静脉乳剂的处方及制备工艺，并对其稳定性、药效学及安全性进行了评价。 以界面张力为评价指标，筛选出蛋黄卵磷脂和进口F-68作为本文使用的混合乳化剂，确定了混合乳化剂的最佳配比。以粒径分布（或稳定参数）为评价指标考察了制备工艺对乳剂粒径的影响。参照zeta电位的测定结果，确定了乳剂的pH值和灭菌条件。以正交试验法对乳剂的处方进行优化，确定了乳剂的处方。对制备乳剂的稳定性进行考察：影响因素和加速试验的考察结果说明自制C-K静脉乳剂较稳定。以超速离心机分离C-K乳剂的各相，HPLC法测定药物在各相中的分布。结果表明C-K大部分分布于乳剂的界面相，仅少量分布于油相和水相中。C-K静脉乳剂与C-K注射液的体外释药均较符合一级释药动力学。药效学试验结果表明，C-K注射液和静脉乳剂在30mg／kg和15mg／kg剂量下均能显著抑制小鼠H₂₂肝癌、lewis肺癌、U₁₄宫颈癌和B₁₆黑色素瘤的生长，且静脉乳剂的毒性较低，其抑瘤作用强于注射液。利用S₁₈₀腹水瘤小鼠研究了C-K注射液和静脉乳剂对小鼠存活期的影响。结果表明，相同剂量下，静脉乳剂对荷瘤小鼠生命存活期的延长作用明显强于注射液。小鼠急性毒性研究表明，C-K静脉乳剂的LD₅₀是注射液的2.3倍，毒性明显小于注射液。 本文研制的C-K静脉乳剂理化性质稳定，毒性低，具有良好的开发前景。更多还原

【Abstract】 In this article, we had studied on the formulation and preparation technique of ginsenoside C-K intravenous emulsion and evaluated its physico-chemical stabilities、pharmacodynamics and safety.Refined soybean phospholipid and F-68 were chose as emulsifiers when the judgemental criterion was interfacial tension. According with the particle size distribution （or Ke ）of emulsion we found the best proportion of the two emulsifiers. The pH values and the condition of steam sterilization were confirmed referring to the zeta potential. The preparation techniques were selected by orthogonal method and had a good result. The C-K intravenous emulsion had steady physico-chemical properties after storing in accelerative test for 6 months and in influencing factor test for 10 days . All phases of C-K intravenous emulsion were separated by overspeed centrifuge and were determined by HPLC. Most of the C-K in the intravenous emulsion were in the interfacial phase and a small quantity of C-K distributed in water phase and oil phase. The release kinetics of C-K emulsion and solution in vitro complied with first order model. C-K intravenous emulsion and solution could effectively restrain the growth of H₂₂ liver cancer、 lewis lung cancer、 U₁₄ cervices cancer and B₁₆ melanin tumour at the dosage of 15mg/kg and 30mg/kg respectively. In contrast to the solution ,the C-K intravenous emulsion had better effect on antitumour. Using S₁₈₀ ascites tumour mice we studied the effect of C-K intravenous emulsion and solution on the life-timeof mice.The result displayed that the intravenous emulsion could prolong the更多还原