一种蒽吡唑类抗肿瘤药物DuP 937在水溶液中与七（2,6-二-O-甲基）-β-环糊精络合时的稳定性。

Stabilization of an anthrapyrazole antitumour agent, DuP 937, on complexation with heptakis(2,6-di-O-methyl)-beta-cyclodextrin in aqueous solution.

作者信息

Raghavan K, Nemeth G, Gray D, Hussain M A

机构信息

DuPont Merck Pharmaceutical Co., Experimental Station, Wilmington, DE 19880-0400.

出版信息

J Pharm Biomed Anal. 1994 Oct;12(10):1259-64. doi: 10.1016/0731-7085(94)00063-8.

DOI:10.1016/0731-7085(94)00063-8

PMID:7841220

Abstract

DuP 937, an anthrapyrazole antitumour agent that is chemically unstable in aqueous solution, was shown, by absorption spectroscopy, to form an inclusion complex with heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DM beta CD) in aqueous solution. Proton nuclear magnetic resonance spectroscopy was used to determine the stoichiometry and association constant of the complex. The 1:1 stoichiometry of the complex was established by the continuous variation method by following changes in the chemical shifts of aromatic protons of DuP 937. The complex association constants determined by different techniques used in this study were in the same order of magnitude. The kinetics of degradation of DuP 937 in aqueous solution were investigated as a function of DM beta CD concentration at pH 5.5 and 60 degrees C. The results indicated about a seven-fold increase in the stability of DuP 937 in the presence of DM beta CD in aqueous solution.

摘要

DuP 937是一种在水溶液中化学性质不稳定的蒽吡唑类抗肿瘤药物。通过吸收光谱法表明，它在水溶液中能与七（2,6 - 二 - O - 甲基）-β-环糊精（DMβCD）形成包合物。利用质子核磁共振光谱法测定该复合物的化学计量比和缔合常数。通过连续变化法，跟踪DuP 937芳香族质子化学位移的变化，确定了复合物的1:1化学计量比。本研究中使用不同技术测定的复合物缔合常数在同一数量级。在pH 5.5和60℃条件下，研究了DuP 937在水溶液中的降解动力学与DMβCD浓度的关系。结果表明，在水溶液中存在DMβCD时，DuP 937的稳定性提高了约7倍。