布洛芬前药及其聚乙二醇化衍生物的合成与水解行为

Synthesis and hydrolytic behavior of ibuprofen prodrugs and their PEGylated derivatives.

作者信息

Davaran Soodabeh, Rashidi Mohammad Reza, Hanaee Jalal, Hamidi Ali A, Hashemi Mahdi

机构信息

Drug Applied Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Drug Deliv. 2006 Sep-Oct;13(5):383-7. doi: 10.1080/10717540500456007.

DOI:10.1080/10717540500456007

PMID:16877314

Abstract

Polyethylene glycol (PEG) derivatives of ibuprofen were prepared by esterification of PEG monosuccinate with hydroxy ethyl ester (HEE), hydroxy ethylamide (HEA), and hydroxy ethyl thioester (HET) of ibuprofen. Hydrolysis of HEE-PEG, HEA-PEG, and HET-PEG were studied in vitro with or without esterases to investigate the applicability of these PEGylated prodrugs. The polymeric prodrugs released major fraction of the parent drug (ibuprofen) and a small fraction of hydroxy ethyl derivatives after 48 hr. In HET-PEG, the amount of drug release was higher than HEE-PEG and HEA-PEG. The difference between acidic and alkali buffered solutions was considerable. In human plasma, 50% of drug was released after 150 hr incubation at 37 degrees C from HET-PEG.

摘要

通过布洛芬的聚乙二醇单琥珀酸酯与布洛芬的羟乙酯（HEE）、羟乙酰胺（HEA）和羟乙硫酯（HET）进行酯化反应，制备了布洛芬的聚乙二醇（PEG）衍生物。在有或没有酯酶的情况下，对HEE-PEG、HEA-PEG和HET-PEG的水解进行了体外研究，以考察这些聚乙二醇化前药的适用性。48小时后，这些聚合物前药释放出大部分母体药物（布洛芬）和一小部分羟乙衍生物。在HET-PEG中，药物释放量高于HEE-PEG和HEA-PEG。酸性和碱性缓冲溶液之间的差异相当大。在人血浆中，HET-PEG在37℃孵育150小时后释放出50%的药物。