大分子前药 XI. 聚合物 - 雌二醇缀合物的合成与表征

Macromolecular prodrugs XI. Synthesis and characterization of polymer-estradiol conjugate.

作者信息

Zovko M, Zorc B, Novak P, Tepes P, Cetina-Cizmek B, Horvat M

机构信息

Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovacića, 1, 10000 Zagreb, Croatia.

出版信息

Int J Pharm. 2004 Nov 5;285(1-2):35-41. doi: 10.1016/j.ijpharm.2004.07.013.

DOI:10.1016/j.ijpharm.2004.07.013

PMID:15488677

Abstract

Estradiol-3-benzoate (EB), an ester derivative of the main oestrogen hormone estradiol, was chemically modified and bound to poly(alpha,beta-(N-2-hydroxyethyl-DL-aspartamide))-poly(alpha,beta-(N-2-aminoethyl-DL-aspartamide)) copolymer (PAHA). EB was first converted to estradiol-3-benzoate-17-(benzotriazole-1-carboxylate), which readily reacted with amino groups in PAHA affording the polymer-drug conjugate PAHA-EB. In PAHA-EB estradiol moiety was covalently bound to the polymeric carrier by carbamate linkage, through non-toxic ethylenediamine spacer. The synthesized compound is a potential hydrosoluble estradiol prodrug.

摘要

雌二醇-3-苯甲酸酯（EB）是主要雌激素激素雌二醇的酯衍生物，经过化学修饰后与聚（α，β-（N-2-羟乙基-DL-天冬酰胺））-聚（α，β-（N-2-氨基乙基-DL-天冬酰胺））共聚物（PAHA）结合。EB首先转化为雌二醇-3-苯甲酸酯-17-（苯并三唑-1-羧酸酯），它能与PAHA中的氨基迅速反应，得到聚合物-药物缀合物PAHA-EB。在PAHA-EB中，雌二醇部分通过无毒的乙二胺间隔基，经氨基甲酸酯键共价连接到聚合物载体上。合成的化合物是一种潜在的水溶性雌二醇前药。