摘要
目的:研究盐酸常山碱的理化性质并考察其脂质体包封率的测定方法。方法:采用HPLC测定盐酸常山碱的含量,流动相乙睛-水-三乙胺-冰乙酸(9∶91∶0.35∶0.75),检测波长265nm;通过摇瓶法测定其在不同pH范围内的油水分配系数,并考察在125℃,30min灭菌后盐酸常山碱在不同pH磷酸盐缓冲液中的稳定性,利用硫酸铵梯度法制备盐酸常山碱脂质体,分别用葡聚糖凝胶和阳离子交换树脂制备微柱,采用离心法使游离药物和脂质体分离,测定药物含量,计算包封率。运用SPSS20.0软件进行t检验,比较上述2种方法测定结果的差异。结果:在pH6~9时,盐酸常山碱的油水分配系数随着pH的升高而增大,油水分配系数处于0.016~1.44,盐酸常山碱灭菌后回收率在37.16%~57.91%,葡聚糖凝胶微柱离心法和阳离子交换树脂微柱离心法测得脂质体的包封率结果无显著性差异。结论:盐酸常山碱适合制成脂质体,但其稳定性并不理想,故在制备工艺中应严格控制实验温度。葡聚糖凝胶微柱离心法和阳离子交换树脂微柱离心法均可以较好地测定盐酸常山碱脂质体的包封率,但比较后建议选择阳离子交换树脂微柱离心法。
Objective: To study on the physical and chemical properties of dichroa alkali hydrochloride and to establish a method for the determination of entrapment efficiency of dichroa alkali hydrochloride liposomes.Method: HPLC was used to determine the content of dichroa alkali hydrochloride with mobile phase of acetonitrilewater-triethylamine-glacial acetic acid(9 ∶ 91 ∶ 0. 35 ∶ 0. 75) and detection wavelength at 265 nm. The oil-water partition coefficient of this compound in different pH range was measured by shake flask method. The stability of the dichroa alkali hydrochloride in phosphate buffer solution with different pH after sterilization at 125 ℃ for 30 min was investigated. Ammonium sulfate gradient method was used to prepare dichroa alkali hydrochloride liposomes.The microcolumn was prepared by dextran gel and cation exchange resin,respectively. Then the free drug and liposome were separated by centrifugation,the drug content was measured,and the encapsulation efficiency was calculated. The t-test was performed using SPSS 20. 0 software,the differences between these two methods were compared. Result: In the pH 6-9,the oil-water partition coefficient of dichroa alkali hydrochloride increased with increasing of pH,which was between 0. 016 and 1. 44;the recovery rate of dichroa alkali hydrochloride after sterilization was 37. 16%-57. 91%. Between the dextran gel microcolumn centrifugation and the cation exchange resin microcolumn centrifugation,there was no significant difference in the entrapment efficiency of the liposomes.Conclusion: Dichroa alkali hydrochloride is suitable for preparation of liposomes. However,its stability is not ideal,so the experimental temperature should be strictly controlled in the preparation process. Dextran gel microcolumn centrifugation and cation exchange resin microcolumn centrifugation can be used to determine the entrapment efficiency of dichroa alkali hydrochloride liposomes, and the cation exchange resin microcolumn centrifugation is suggested after comparison.
作者
王凤玉
张保献
张广平
聂其霞
臧琛
马丽娜
苏萍
侯红平
杨依霏
张钟秀
马梦
叶祖光
WANG Feng-yu;ZHANG Bao-xian;ZHANG Guang-ping;NIE Qi-xia;ZANG Chen;MA Li-na;SU Ping;HOU Hong-ping;YANG Yi-fei;ZHANG Zhong-xiu;MA Meng;YE Zu-guang(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2019年第1期177-182,共6页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家“重大新药创制”科技重大专项(2015ZX09501004,2017ZX09101002-001-006)
北京市自然科学基金项目(7174327)
关键词
盐酸常山碱
脂质体
油水分配系数
稳定性
包封率
微柱离心法
硫酸铵梯度法
dichroa alkali hydrochloride
liposomes
oil-water partition coefficient
stability
encapsulation efficiency
microcolumn centrifugation method
ammonium sulfate gradient method
作者简介
第一作者:王凤玉,在读博士,从事中药新剂型研究,E-mail:yiyun1888@163.com;通信作者:叶祖光,研究员,从事中药药理及毒理学研究,Tel:010-84252805,E-mail:yezuguang@sina.com.
