叶下珠配方颗粒与饮片汤剂化学等量相关性及药效等效性研究  

Chemical equivalence correlation and pharmacodynamic equivalence of dispensing granules of Phyllan-thus urinaria and slice decoction

作　　者：朱仙慕 黄群[1] 陈丹[1] 谢平[1] 马国萍[1] ZHU Xianmu;HUANG Qun;CHEN Dan;XIE Ping;MA Guoping(Department of Pharmacy,Fujian Univer-sity of TCM,Fujian Fuzhou 350122,China)

机构地区：[1]福建中医药大学药学院,福建福州350122

出　　处：《中国医院药学杂志》2024年第20期2346-2356,共11页Chinese Journal of Hospital Pharmacy

基　　金：福建省科技计划项目(编号:2010Y2004);福建省科技引导性项目(编号:2019Y0037);福建省科技引导性项目(编号:2019Y0038)。

摘　　要：目的:考察叶下珠配方颗粒与饮片汤剂的化学等量相关性,评价二者保肝护肝药效等效性。方法:建立叶下珠配方颗粒与饮片汤剂高效液相色谱(HPLC)特征图谱共有模式,高效液相色谱-四极杆飞行时间串联质谱(LC-QTOF-MS/MS)法辨识指认共有峰;紫外-可见分光光度(UV)法测定有效部位总多酚含量,HPLC法测定柯里拉京、没食子酸、鞣花酸3个特征效应组分含量;并结合上述多指标综合评价等效比模型计算,研究二者间的化学等量性及剂量比。采用四氯化碳致小鼠肝损伤模型,考察比较分别给予小鼠等量等效剂量比的配方颗粒、饮片汤剂后,血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平及肝脏组织的肝指数、丙二醛(MDA)水平、总超氧化物歧化酶(SOD)活性,考察新鲜肝脏外观和肝组织病理切片的形态学,探究二者对肝脏损伤的保护程度及保肝护肝药效等效性。结果:辨识指认配方颗粒与饮片汤剂特征图谱共有峰12个,二者相似度均>0.900;叶下珠配方颗粒与饮片的等量等效剂量比约为1∶5,以此剂量比给药,配方颗粒、饮片汤剂均能显著降低肝脏指数及MDA含量,提高SOD活性,降低血清ALT、AST含量(均P<0.05),且肝脏外观及肝组织病理切片的病变程度均有所改善,提示二者具有等效的抗肝损伤及保肝作用。结论:叶下珠配方颗粒与饮片汤剂的效应组分群整体表征出良好的相似性和化学等量相关性及稳定性,1 g叶下珠配方颗粒相当于5 g饮片;以1∶5等量等效剂量比用药,二者具有保肝护肝药效等效性。OBJECTIVE To explore the chemical equivalence correlation between dispensing granules of Phyllanthus uri-naria and slice decoction and evaluate the equivalence of the two for hepatic protection.METHODS High performance liquid chromatography(HPLC)was utilized for establishing a common pattern of the characteristic spectrum of P.urinaria dispensing granules and slice decoction,and identify the common peaks by LC-QTOF-MS/MS method.Based upon established ultraviolet(UV)method for determining total polyphenol content of effective parts,HPLC was employed for determining the contents of three characteristic effective components of corilagin,gallic acid and ellagic acid.The above-mentioned multi-indicator compre-hensive evaluation equivalence ratio calculation model was used for examining chemical equivalence and dose ratio between the two.Using murine hepatic injury model induced by carbon tetrachloride,serum levels of alanine transaminase(ALT)and aspar-tate transaminase(AST),liver index,malondialdehyde(MDA)and superoxide dismutase(SOD)of hepatic tissue were mea-sured after equal doses of dispensing granules and slice decoction.Appearance of fresh liver and morphology of hepatic tissue pathological sections were utilized for assessing the degree of protection against liver injury and the efficacy equivalence of hepato-protective drug.RESULTS A total of 12 characteristic peaks with a common pattern in the spectra of formula granules and decoc-tion pieces were identified.The similarity between the two was>0.900.The equivalent dose ratio of dispensing granules of P.urinaria to slice decoction was approximately 1∶5.At this dose ratio,both dispensing granules and slice decoction demonstrated marked reductions in hepatic parameters and MDA content and higher SOD activity.Additionally,serum levels of ALT and AST declined(all P<0.05).Furthermore,hepatic appearance and degree of lesions in pathological sections of hepatic tissue improved.It suggested that both dispensing granules of P.urinaria and slice decoction exerted equiv

关 键 词：叶下珠配方颗粒 饮片汤剂 特征图谱 化学等量相关性 等量等效比 保肝护肝 等效性 

分 类 号：R917[医药卫生—药物分析学] R284.1[医药卫生—药学]