热毒宁注射液中绿原酸的降解动力学研究  

Study on degradation kinetics of chlorogenic acid in reduning injection

作　　者：邱喜龙[1] 任晓亮[1] 张慧杰[1] 萧伟[2,3] 戚爱棣[1] 

机构地区：[1]天津中医药大学中药学院,天津300193 [2]江苏康缘药业股份有限公司,连云港222001 [3]中药制药过程新技术国家重点实验室(筹),连云港222001

出　　处：《药物分析杂志》2012年第12期2240-2245,2179,共7页Chinese Journal of Pharmaceutical Analysis

基　　金：中药制药过程新技术国家重点实验室开放基金课题(SKL2010Z0401);高等学校博士学科点专项科研基金项目(20111210120006);国家自然科学基金青年基金项目(81102732)

摘　　要：目的:研究热毒宁注射液中绿原酸(chlorogenic acid,CHA)在不同pH和温度条件下降解反应的动力学特征。方法:采用高效液相色谱法(HPLC)考察不同pH和温度下绿原酸对照品水溶液及热毒宁注射液中绿原酸的含量变化,利用化学反应动力学的方法计算绿原酸在不同环境下的降解反应动力学参数,用阿仑尼乌斯公式预测其有效期(t0.9)、半衰期(t0.5)和活化能(energy of activation,Ea)。结果:绿原酸在不同pH和温度下的降解反应均遵循一级动力学规律,在pH7水溶液中绿原酸的t0.9=22 d、t0.5=104 d、Ea=90.89 kJ.mol-1;在热毒宁注射液中绿原酸的t0.9=31 d、t0.5=203 d、Ea=140.49 kJ.mol-1。结论:绿原酸在水溶液及热毒宁注射液中均在酸性、低温条件下较稳定。同样条件下,绿原酸在热毒宁注射液中的稳定性都要高于绿原酸水溶液。可根据绿原酸降解动力学模型,用于热毒宁注射液有效性和稳定性的评价。Objective：To investigate the degradation kinetic characteristics of chlorogenic acid（CHA） in reduning injection under different pH and temperature conditions. Methods：HPLC was employed for the study;the concentra- tion changes of CHA in aqueous solution and reduning injection under different pH and temperature conditions were determined. Based on the chemical reaction kinetic, the parameters of degradation kinetics were calculated. The acti- vation energy and shelf life were evaluated with Arrhenius equation. Results： Our results indicated that thermal deg- radation kinetic model of CHA in aqueous solution and reduning injection was a first - order degradation kinetic process. The period of validity （t0.9） were 22 and 31 days ;the half - life period （t0.5） were 104 and 203 days un- der pH7 in aqueous solution and reduning injection. The energy of activation （Ea） was 90. 89 kJ · mol-Xin aqueous solution and 140. 49 kJ · tool-1 in reduning injection. Conclusions：CHA is more stable in acidic and low tempera- ture conditions both in aqueous solution and reduning injection. Under the same condition, CHA in reduning injec- tion was more stable than in aqueous solution. The kinetic profile can be used for the evaluation of effectiveness and stability of reduning injection.

关 键 词：热毒宁注射液 水溶液 pH 温度 绿原酸 降解动力学 药物稳定性 

分 类 号：R917[医药卫生—药物分析学]