摘要
目的:考察甘草酸对紫杉醇溶解度的增溶作用。方法:将不同比例甘草酸和紫杉醇,不同比例乙醇和紫杉醇进行配伍,采用高效液相色谱法检测紫杉醇的浓度;并采用电导率法检测甘草酸-紫杉醇溶液的临界胶束浓度。结果:在乙醇比例为7.5%且甘草酸浓度为10 mmol·L^(-1)时,紫杉醇达到最佳溶解度(823.38±14.41)μg·mL^(-1),较紫杉醇水中溶解度增加约1 000倍(0.67→823μg·mL^(-1)),较紫杉醇在7.5%乙醇液中溶解度增加约100倍(8.51→823μg·mL^(-1))。紫杉醇-甘草酸溶液(含7.5%乙醇)的临界胶束浓度为0.42 mmol·L-1,证明其在更低浓度下能形成胶束状态。结论:首次发现在甘草酸和低体积分数乙醇的协同作用下,紫杉醇水中溶解度得到有效增加,鉴于甘草酸的两亲性,安全性和一些特殊的药理活性,为制备基于甘草酸为载体的新型紫杉醇制剂奠定基础。
OBJECTIVE To study solubilization effects of glycyrrhizic acid on paclitaxel in water.METHODS Concentrations of paclitaxel were detected by high performance liquid chromatography（HPLC）methods.Glycyrrhizic acid was added in water co-existed with low concentration of ethanol,and critical micelle concentration of paclitaxel-glycyrrhizic acid solution was also detected by conductivity method.RESULTS Phase-solubility test of paclitaxel showed that PTX solubility could reach to（823.38±14.41）μg·mL-1 as the optimal ethanol percentage（7.5%）and the optimal concentration of GA（10 mmol·L-1）was used,which was about 1 000-folds（0.67→823μg·mL-1）compared with solubility of PTX in water,and about 100-folds（8.51→823μg·mL-1）compared with solubility of PTX in ethanol solution（7.5%）.Critical micelle concentration of paclitaxel-glycyrrhizic acid solution was 0.42 mmol·L-1,which proved that paclitaxel-glycyrrhizic acid solution tended to be more stable.CONCLUSION It is for the first time to find that solubility of PTX can be greatly improved by synergistic effects of ethanol at low concentration and glycyrrhizic acid,which has laid a good foundation for new preparations of paclitaxel,based on amphipathic properties and safety and special pharmacological activities of glycyrrhizic acid.
作者
杨富恒
刘旭东
刘思佳
梁倩莹
蔡云
张韫琪
李国锋
YANG Fu-heng LIU Xu-dong LIU Si-jia LIANG Qian-ying CAI Yun ZHANG Yun -qi LI Guo-feng(Nanfang Hospital, Southern Medical University, Guangzhou Guangdong 510515, China Maternal and Child Health Care Hospital of Zhuhai, Guangdong Zhuhai 519000, China)
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2016年第21期1873-1877,共5页
Chinese Journal of Hospital Pharmacy
基金
广东省自然科学基金项目(编号:2015A030313281)
关键词
紫杉醇
甘草酸
溶解度
临界胶束浓度
palitaxel
glycyrrhizic acid
solubility
critical micelle concentration
