基于等温滴定量热技术的清开灵注射液临床联合用药相互作用表征研究  

Characterization of interaction in Qingkailing Injection with clinic administration based on isothermal titration calorimetry

作　　者：鄢丹[1] 陈龙虎[1,2] 冯雪[1] 邱玲玲[1] 闫琰[1] 张萍[1] 杜晓曦[3] 肖小河[1] 

机构地区：[1]解放军第302医院全军中药研究所,北京100039 [2]成都中医药大学药学院,四川成都611137 [3]国家食品药品监督管理局药品评价中心,北京100045

出　　处：《中草药》2012年第11期2217-2221,共5页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81173542;81274078);北京市自然科学基金资助项目(7112128);中药资源系统研究与开发利用省部共建国家重点实验室培育基地开发基金资助项目(ZYCD028)

摘　　要：目的建立一种揭示中西药注射剂临床联合用药相互作用表征的新方法。方法以清开灵注射液为模式药,分别加入注射用头孢唑肟钠与5%葡萄糖注射液(简称葡糖液),采用等温滴定量热法(ITC)分别考察药物间相互作用,以热力学参数吉布斯自由能(ΔG)、焓变(ΔH)、熵变(ΔS)判断溶合反应类型,通过对比不同注射剂混合前后化学指纹图谱特征信息对结果进行佐证。结果清开灵注射液与头孢唑肟钠滴定过程中测得|ΔH|>T|ΔS|,为焓驱动反应,且释放热量较大,提示两者之间的相互作用以化学反应为主,内在物质发生改变。清开灵注射液与5%葡糖液溶合时|ΔH|<T|ΔS|,为熵驱动反应,且反应活性谱显示放热较少,提示两者之间的相互作用以物理反应为主,活性成分仅被溶解稀释,未发生质变。上述结果也得到了化学指纹图谱的佐证。结论 ITC具有简便快捷、高灵敏度等优势,可用于清开灵注射液临床联合用药相互作用表征的研究,也为其他中西药注射剂联合用药的相容性评价提供了参考。Objective To establish a new method used for revealing the charcterization of interaction between Chinese and Western medicinal injections. Methods Isothermal titration calorimetry （ITC） was applied to evaluating the interaction in Qingkailing Injection （QKLI, as mode drug） with Ceftizoxime Sodium Injection （CSI） and 5% Glucose Injection （5% GI）. The diversification of Gibbs free energy （AG）, enthalpy （△H）, and entropy （AS） were determined to judge the reaction types of colliquefaction procedures of different injections. Meanwhile, the fingerprints of QKLI before and after combined with the various injections were compared to validate the results. Results During the titration procedure of QKLI and CSI, IAHI 〉 T ]ASp, that was to say the reaction was enthalpy-driving. And the reactive profile indicated that a great deal of heat gave out during the procedure. Obviously, chemical reactions happened and the internal component changed. On the other side, the reaction of QKLI combined with 5% GI was entropy-driving, because 丨△H丨 〈 T 丨△S丨. The reactive profile showed there was only a little heat released. So non-chemical reactions happened and the major ingredients did not change. In addition, the results of ITC were validated by the fingerprints. Conclusion ITC, with the virtue of convenience, speediness as well as highsensitivity, could be utilized to evaluate the interaction in QKLI with clinic administration. Meanwhile, ITC could be applied to the evaluation on compatibility of other kinds of Chinese and Western medicinal injection combination.

关 键 词：清开灵注射液 头孢唑肟钠注射液 葡萄糖注射液 药物相互作用 等温滴定量热法 

分 类 号：R969.2[医药卫生—药理学]