基于序贯分析策略的双黄连注射液与注射用氨苄西林钠联合用药合理性评价  

Rationality evaluation of Shuanghuanglian Injection combined with Ampicillin Sodium for Injection based on sequential analysis

作　　者：许杨 李江玲 刘爽 王真真 黄明月 王爱婷 刘贤武[1] 鄢丹 XU Yang;LI Jiang-ling;LIU Shuang;WANG Zhen-zhen;HUANG Ming-yue;WANG Ai-ting;LIU Xian-wu;YAN Dan(School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China;Beijing Institute of Clinical Pharmacy,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China;Beijing Key Laboratory of Bio-characteristic Profiling for Evaluation of Rational Drug Use,Beijing 100038,China)

机构地区：[1]成都中医药大学药学院,四川成都611137 [2]首都医科大学附属北京友谊医院北京市临床药学研究所,北京100050 [3]临床合理用药生物特征谱学评价北京重点实验室,北京100038

出　　处：《中国中药杂志》2022年第12期3380-3385,共6页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81773891,82130112);北京市优秀人才“青年拔尖团队”项目(2018000021223TD09);北京市医院管理中心“登峰”计划专项(DFL20190702)。

摘　　要：体现药物联合应用的合理性评价方法的薄弱长期制约了其临床使用。为突破现有评价方法的局限,该文以双黄连注射液为模式药,建立“物理-化学-生物”序贯分析评价方法,为提升临床联合用药的安全性与有效性提供新的思路。采用不溶性微粒、等温滴定量热(isothermal titration calorimetry,ITC)、实时无标记细胞(real time cellular analysis,RTCA)方法,评价双黄连注射液与注射用氨苄西林钠临床联合用药的合理性。结果显示,通过不溶性微粒检测仪检测,两者配伍后的溶液不溶性微粒数大于10μm,符合《中国药典》标准,而不溶性微粒数大于25μm,不符合《中国药典》标准;且ITC检测发现两者在溶合过程中,吉布斯自由能变化ΔG小于0,说明该过程自发进行,为焓驱动反应,提示两者之间的相互作用以化学反应为主,内在物质可能发生改变;RTCA法进一步研究发现与对照组相比:单药组对HEK293T细胞的生长基本无抑制作用,而联合用药组对HEK293T细胞的生长产生较强的抑制作用,提示其对HEK293T细胞具有毒性作用。该研究表明,双黄连注射液与注射用氨苄西林钠联用时发生了药物相互作用,易产生毒性作用,提示临床不宜联用。该研究依托等温滴定量热、细胞动态分析关键技术,通过物理、化学、生物角度序贯分析,获得药物分子相互作用的特征,不仅适用于该文模式药的研究,也为其他中西药注射剂合理用药提供参考。The lack of rationality evaluation method for drug combination has long restricted its clinical application.In view of this,this study took Shuanghuanglian Injection as model drug and established a"physical-chemical-biological"sequential analysis method,which is expected to provide clues for improving the safety and effectiveness of clinical drug combination.With the methods of insoluble particle testing,isothermal titration calorimetry(ITC),and real time cellular analysis(RTCA),the rationality of Shuanghuanglian Injection combined with Ampicillin Sodium for Injection was assessed.The results showed that the number of insoluble particles>10μm in the solution of the combination met the standard of Chinese Pharmacopoeia,while the number of insoluble particles>25μm did not meet the standard.ITC detection demonstrated that the change of Gibbs free energy(ΔG)was less than 0 during the fusion process,indicating that the process was spontaneous and enthalpy-driven reaction.Therefore,the interaction between the two was mainly chemical reaction,and the internal substances may change.RTCA found that Shuanghuanglian Injection alone and Ampicillin Sodium for Injection alone basically had no inhibitory effect on the growth of HEK293 T cells,while the combination of the two suppressed the growth of HEK293 T cells,suggesting that the combination was toxic to HEK293 T cells.This study showed that Shuanghuanglian Injection and Ampicillin Sodium for Injection reacted,yielding toxicity.This suggested that the two should not be combined for application.With the"physical-chemical-biological"sequential analysis,the molecular interaction of drugs was clarified.The method can be further applied for evaluating the rationality of other Chinese and western medicine injections.

关 键 词：联合用药 双黄连注射液 注射用氨苄西林钠 合理性 序贯分析 

分 类 号：R969.3[医药卫生—药理学]