基于体内过程分析的中西药注射剂联合序贯用药“时间窗”的探索性研究

项目名称： 基于体内过程分析的中西药注射剂联合序贯用药“时间窗”的探索性研究

项目编号： No.81503247

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 张雅铭

作者单位： 中国人民解放军总医院

项目金额： 18万元

中文摘要： 中西药注射剂联用的不良反应日益严峻。临床上为了避免中西药注射剂联用产生不良反应，仅凭经验在两种药物之间输入生理盐水，缺乏相应的临床/实验研究基础，这或将导致潜在的安全性问题。合理的给药间隔时间（“时间窗”）研究作为减少中西药注射剂联用不良反应、指导临床安全用药的重要课题之一，目前并没有受到应有的重视。本项目以中西药注射剂的体内过程分析倒推“时间窗”为切入点，采用UPLC-Q-TOF/MS、模式识别技术，以双黄连注射剂与利巴韦林注射剂为研究对象,以单用组为对照，重点考察两药不同联用时间间隔下体内成分动态变化规律（血清指纹图谱、消除曲线等），根据血清代谢轮廓对比分析不同联用时间的体内过程信息差异，采用模式识别技术，初步确定中西药注射剂序贯联用“时间窗”（阈值范围），全程辅以活细胞指纹谱监测与药理学验证，以期为“时间窗”研究的模式探索、中西药注射剂联用的规范完善提供依据。

中文关键词： 联合用药；时间窗；体内过程分析；中药注射剂；西药注射剂

英文摘要： The adverse reaction of the combination of Chinese and western medicine injection is increasingly serious. In order to avoid the injection-mix adverse reaction in vivo, physiological saline is used clinically between the two drugs only by experience, lack of corresponding clinical/laboratory research foundation, which may lead to potential safety problems. As one of the important topics in the clinical medication safety, reasonable combination time interval ( time window ) research are currently no worthy attention. Based on injection process analysis in vivo ascending time window, UPLC-Q-TOF/MS & pattern recognition technology was applied in this project, to investigate the body composition and its dynamic change rule (serum fingerprint, eliminate curve, etc.) of Shuanghuanglian injection combined with ribavirin injection under different combination interval. According to the serum metabolic profile analysis of process information in the body of different combination interval, discriminant equation and initial time limit are supposed to be established to ensure the safety of the Chinese and western medicine injection sequential combination (threshold range), accompanied by combination evaluation in vitro, bio-response profile of living cells and pharmacology validation. In order to provide the basis for exploring time window research model and perfect the Chinese and western medicine injection combination specification.

英文关键词： combined medication;time window ;process analysis in vivo ;Chinese medicine injection;western medicine injection