七（2,6-二-O-甲基）-β-环糊精与抗肿瘤药物苯丁酸氮芥的络合作用

Heptakis(2,6-di-O-methyl)-beta-cyclodextrin complexation with the antitumor agent chlorambucil.

作者信息

Green A R, Guillory J K

机构信息

College of Pharmacy, University of Iowa, Iowa City 52242.

出版信息

J Pharm Sci. 1989 May;78(5):427-31. doi: 10.1002/jps.2600780517.

DOI:10.1002/jps.2600780517

PMID:2746481

Abstract

The effects of heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DIMEB) and of beta-cyclodextrin (beta-CD) on the aqueous solubility and stability of chlorambucil (CHL) have been compared. In the presence of 1.3 x 10(-3) M DIMEB, there is a greater than 20-fold increase in the stability of chlorambucil at 37 degrees C, pH 4.13. Aqueous solubility of CHL is increased more than 40-fold in the presence of 1.74 x 10(-2) M DIMEB when the solubility is studied under conditions where degradation is minimized (3.0 degrees C, pH 4.13). In the presence of 1.3 x 10(-3) M beta-CD, there is a fourfold increase in the stability, and with 1.74 x 10(-2) M beta-CD, there is a threefold increase in the aqueous solubility of CHL under similar conditions. Stability constants of the CHL complex with DIMEB were determined kinetically and spectrophotometrically under various experimental conditions assuming 1:1 inclusion complex formation.

摘要

已比较了七（2,6 - 二 - O - 甲基）-β - 环糊精（DIMEB）和β - 环糊精（β - CD）对苯丁酸氮芥（CHL）的水溶性和稳定性的影响。在存在1.3×10⁻³ M DIMEB的情况下，在37℃、pH 4.13时苯丁酸氮芥的稳定性增加超过20倍。当在降解最小化的条件下（3.0℃、pH 4.13）研究溶解度时，在存在1.74×10⁻² M DIMEB的情况下，CHL的水溶性增加超过40倍。在存在1.3×10⁻³ M β - CD的情况下，稳定性增加四倍，而在1.74×10⁻² M β - CD存在下，在类似条件下CHL的水溶性增加三倍。在各种实验条件下，假设形成1:1包合物，通过动力学和分光光度法测定了CHL与DIMEB络合物的稳定常数。