炼蜜用量对附子理中丸中9种生物碱类成分药代动力学的影响  

Effect of Refined Honey Amount on Pharmacokinetics of 9 Different Alkaloids in Fuzi Lizhongwan

作　　者：甘嘉荷 王淳 宋志前 刘元艳[2] 宁张弛 马新玲 赵思宇[2] 刘振丽 

机构地区：[1]中国中医科举院中医基础理论研究所,北京100700 [2]北京中医药大学中药学院,北京100102

出　　处：《中国实验方剂学杂志》2018年第3期90-96,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：中央级科研院所自主选题项目(YZ-1542)

摘　　要：目的：建立大鼠口服附子理中丸2种剂型后不同时间点血浆中9种生物碱类成分含量的测定方法,考察辅料炼蜜对附子中主要生物碱类成分药代动力学行为的影响。方法：SD大鼠分别给予2种含炼蜜量不同的附子理中丸大蜜丸（19.44 g·kg^-1）和水蜜丸（19.22 g·kg^-1）,于给药后不同时间点取血,采用RRLC-TQ-MS测定血浆中9种生物碱类成分的血药浓度,绘制血药浓度-时间曲线,计算药物动力学参数。结果：在大鼠血浆中检测到9种生物碱中的8种。双酯型生物碱乌头碱、新乌头碱、次乌头碱的药-时曲线下面积（AUC）,药峰浓度（Cmax）,达峰时间（Tmax）和半衰期（t1/2）均为大蜜丸〉水蜜丸,而清除率（CL）为大蜜丸〈水蜜丸;单酯型生物碱苯甲酰新乌头原碱、苯甲酰次乌头原碱的AUC,Tmax和t1/2均为大蜜丸〈水蜜丸,而Cmax和CL为大蜜丸〉水蜜丸,苯甲酰乌头原碱未被检测到;醇胺型生物碱乌头原碱、新乌头原碱和次乌头原碱的AUC,Tmax和t1/2均为大蜜丸〈水蜜丸,而Cmax和CL为大蜜丸〉水蜜丸。结论：炼蜜能够影响附子理中丸中制附子主要生物碱成分的药动学特征,炼蜜量大的大蜜丸与炼蜜量小的水蜜丸比较,作为制附子的特征性标志物双酯型生物碱在体内达到药峰时间延长,消除速度减慢,提示炼蜜在复方中能够起到延缓吸收的作用。Objective： To establish a method for the determination of nine alkaloids in plasma at different time points after oral administration of two dosage forms of Fuzi Lizhongwan,in order to determine refined honey whether have any impact on the pharmacokinetic behavior of the main alkaloids. Method： SD rats were given two different kinds of Fuzi Lizhongwan（big honeyed pill of 19. 44 g·kg^-1 and water-honeyed pill of 19. 22 g·kg^-1）with different amount of honey. Blood concentrations were measured at different time points after administration,and the concentrations of 9 alkaloids in the plasma were determined by RRLC-TQ-MS. The plasma concentrationtime curves were drawn and the pharmacokinetic parameters were calculated. Result： Eight of nine alkaloids were detected in rat plasma. For diester alkaloids, the AUC, Cmax,Tmaxand t1/2 of aconitine, mesaconitine and hypaconitine were big honeyed pill water-honeyed pill,and clearance rate（CL） was the big honeyed pill water-honeyed pill. For monoester alkaloids,the AUC,Tmaxand t1/2 of benzoylmesaconine and benzoylhypaconine were big honeyed pill water-honeyed pill, and Cmaxand CL were big honeyed pill water-honeyed pill.Benzoylaconine was not detected. For alcohol amine alkaloids,the AUC,Tmaxand t1/2 of aconine,mesaconine and hypaconine were big honeyed pill water-honeyed pill,and Cmaxand CL were big honeyed pill water-honeyed pill. Conclusion： The refined honey can affect the pharmacokinetic characteristics of the main alkaloid components in Fuzi Lizhongwan. Compared with the water-honeyed pill,times to peak of diester alkaloids in big honeyed pill are extended and the elimination rates are slowed down,which suggesting that refined honey in the formula can play a role in delaying absorption.

关 键 词：药物动力学 炼蜜 附子理中丸 双酯型生物碱 单酯型生物碱 醇胺型生物碱 快速液相色谱串联质谱 

分 类 号：R969.1[医药卫生—药理学] R945[医药卫生—药学]