西黄方主要活性成分在乳腺癌癌前病变大鼠体内血浆药动学及尿排泄比较研究  

Comparison of in vivo plasma pharmacokinetics and urine excretion of main components in Xihuang Formula in rats with precancerous lesions of breast cancer

作　　者：谢建絮 张咏佳 黄潘雯 张永太[1] 王志[1] 冯年平[1] XIE Jian-xu;ZHANG Yong-jia;HUANG Pan-wen;ZHANG Yong-tai;WANG Zhi;FENG Nian-ping(Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;the Tenth People's Hospital of Shanghai,Shanghai 200072,China)

机构地区：[1]上海中医药大学,上海201203 [2]上海市第十人民医院,上海200072

出　　处：《中国中药杂志》2023年第6期1642-1651,共10页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金青年基金项目(81603308);上海中医药大学预算内科研项目(2021LK106)。

摘　　要：分别建立西黄方中乳香-没药提取物主要活性成分11-羰基-β-乙酰乳香酸(AKBA)、β-乳香酸(β-BA)在大鼠血浆、尿中的UPLC-MS/MS分析方法,考察配伍对AKBA、β-BA在大鼠体内的药动学影响,比较其在正常与乳腺癌癌前病变大鼠体内的药动学行为差异。结果显示,与乳香-没药+牛黄提取物组(RM-NH组)、乳香-没药+麝香提取物组(RM-SX组)相比,西黄方正常组血浆中β-BA的AUC_(0-t)、AUC_(0-∞)显著增加(P<0.05或P<0.01),T_(max)减少(P<0.05或P<0.01),C_(max)增加(P<0.01);AKBA与β-BA趋势相同,与RM-SH组相比,西黄方正常组T_(max)减小(P<0.05),C_(max)增加(P<0.01),吸收速率加快;尿排泄结果表明,复方配伍后β-BA、AKBA尿排速率和尿排总量呈减少趋势,但差异无统计学意义。与西黄方正常组相比,乳腺癌癌前病变组血浆中的β-BA表现出AUC_(0-t)、AUC_(0-∞)增加(P<0.05),T_(max)增加(P<0.05),清除率(CL_(Z/F))降低的趋势;AKBA的AUC_(0-t)、AUC_(0-∞)呈增加趋势,体内滞留时间(MRT_(0-t))延长,CL_(Z/F)降低,但与西黄方正常组比较差异无统计学意义;病理状态下β-BA、AKBA的累积尿排泄量与尿排速率降低,表明病理状态可影响β-BA、AKBA的体内过程,使其以原型药物的形式排出量减少,表现出与正常生理状体下不同的药动学特征。该研究建立了UPLC-MS/MS的分析方法,适用于β-BA、AKBA体内药代动力学研究,为西黄方新剂型的开发奠定了一定基础。The UPLC-MS/MS was established for the determination of acetyl-11-keto-beta-boswellic acid(AKBA)andβ-boswellic acid(β-BA),the main active components of Olibanum and Myrrha extracts in Xihuang Formula,in rat plasma and urine.The effects of compatibility on the pharmacokinetic behaviors of AKBA andβ-BA in rats were investigated,and the differences in pharmacokinetic behaviors between healthy rats and rats with precancerous lesions of breast cancer were compared.The results showed that compared with RM-NH and RM-SH groups,the AUC_(0-t)and AUC_(0-∞)ofβ-BA increased(P<0.05 or P<0.01),T_(max)decreased(P<0.05 or P<0.01),and C_(max)increased(P<0.01)after compatibility.The trends of AKBA andβ-BA were the same.Compared with RM-SH group,the T_(max)decreased(P<0.05),C_(max)increased(P<0.01),and the absorption rate increased in the normal group of Xihuang Formula.The results of urinary excretion showed that there was a decreasing trend in the urinary excretion rate and total urinary excretion ofβ-BA and AKBA after compatibility,but there was no statistical difference.Compared with normal group of Xihuang Formula,the AUC_(0-t)and AUC_(0-∞)ofβ-BA increased(P<0.05),T_(max)increased(P<0.05),and the clearance rate decreased in the breast precancerous lesion group.AUC_(0-t)and AUC_(0-∞)of AKBA showed an increasing trend,the in vivo retention time was prolonged,and the clearance rate was reduced,but there was no significant difference compared with the normal group.The cumulative urinary excretion and urinary excretion rate ofβ-BA and AKBA decreased under pathological conditions,indicating that pathological conditions could affect the in vivo process ofβ-BA and AKBA,and reduce their excretion in the form of prototype drugs,showing different pharmacokine-tic characteristics from normal physiological conditions.In this study,UPLC-MS/MS analysis method was established,which was sui-table for in vivo pharmacokinetic analysis ofβ-BA and AKBA.This study laid a foundation for the development of new dosage forms of Xihuang F

关 键 词：西黄方 乳腺癌癌前病变 血浆药动学 尿排泄 

分 类 号：R285.5[医药卫生—中药学]