超微粉碎对七味广枣散体外溶出度及大鼠体内药动学的影响

Effect of ultrafine grinding on the in vitro dissolution and pharmacokinetics of Qiwei Guangzao powder in rats

目的研究超微粉碎对七味广枣散中没食子酸、原儿茶酸和丁香酚的体外溶出度及其在大鼠体内药动学的影响。方法采用高效液相色谱(HPLC)法测定没食子酸、原儿茶酸和丁香酚3种指标成分含量,以普通粉为对照,对七味广枣散超微粉中指标成分在水、人工胃液和人工肠液3种溶出介质中的溶出性能进行评价;SD大鼠灌胃给予七味广枣散普通粉或超微粉(用0.5%CMC-Na混悬),给药后眼眶取血,采用HPLC法测定血浆中丁香酚的质量浓度,LC-MS法测定没食子酸和原儿茶酸的血药浓度,使用DAS 3.0软件计算药动学参数,利用SPSS 19.0软件进行统计学分析,以普通粉为参比,评价七味广枣散超微粉中3种指标成分在大鼠体内的药动学特性。结果七味广枣散超微粉中丁香酚在3种溶出介质中的溶出度始终高于普通粉,而没食子酸和原儿茶酸在溶出开始的短时间内不同程度地高于普通粉,但随着时间的延长,累积溶出率与普通粉趋于一致;七味广枣散超微粉组丁香酚的AUC_(0~720 min)和AUC_(0~∞)分别为普通粉组的1.76倍和2.56倍(P<0.05),没食子酸和原儿茶酸的各药动学参数在七味广枣散超微粉组和普通粉组间差异不具有统计学意义。结论超微粉碎对药材中不同理化性质成分影响不同,难溶性成分所受影响较水溶性成分可能更为显著。

Objective To determine the effect of ultrafine grinding on the in vitro dissolution and pharmacokinetics of gallic acid,protocatechuic acid and eugenol in Qiwei Guangzao powder in rats.Methods The content of gallic acid,protocatechuic acid and eugenol was determined by HPLC,and the dissolution of the index components in water,artificial gastric juice,and artificial intestinal juice was evaluated.SD rats were given common powder or ultrafine powder(suspended with 0.5%CMC-Na)by gavage,and blood was taken from the orbit after the administration.The concentration of eugenol in the plasma was determined by HPLC,and the plasma concentration of gallic acid and protocatechuic acid were determined by LC-MS.The pharmacokinetic parameters were calculated by DAS 3.0 software,and the statistical analysis by SPSS 19.0 software.With common powder as the reference,we evaluated the pharmacokinetics of 3 index components in the ultrafine powder in rats.Results The dissolution rate of eugenol in the ultrafine powder in the 3 dissolution media was much higher than that of the common powder;while the dissolution of gallic acid and protocatechuic acid in the ultrafine powder in the 3 dissolution media was higher than that of the common powder to various degrees shortly after the dissolution,but with time,the cumulative dissolution rate tended to be consistent with that of the common powder.The AUC_(0~720 min) and AUC_(0~∞)of eugenol in the ultrafine powder group were 1.76 times and 2.56 times higher than those in the common powder group,respectively(P<0.05).The pharmacokinetic parameters of gallic acid and protocatechuic acid had no significant difference between the two groups.Conclusion Ultrafine grinding affects components with different physical and chemical properties in medicinal materials.Insoluble components are more easily affected than the water-soluble ones.