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STUDIES ON THE DEVELOPMENT OF VARIOUS TYPES OF DRUG DERIVERY SYSTEM USING CHITIN DERIVATIVES

利用甲壳素衍生物开发各类药物衍生系统的研究

基本信息

批准号：
02555183
负责人：
TOKURA Seiichi
金额：
$ 11.39万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research (B)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1992
项目状态：
已结题

项目摘要

The study has been achieved to apply of water-soluble and biodegradable carboxymethyl-chitin(CM-chitin) for the drug derivery system as a drug carrier. The sustained release of drug of prodrug was achieved by the lysozymic hydrolysis of drug carrier in animal body, since CM-chitin tended to adsorb phenyl group drug in the presence of calcium ion and to entrapp the drug or prodrug by the addition of trivalent iron to CM-chitin through the rigid gel formation. A two step hydrolysis was proposed to the controlled release of drug in animal body, when pendant type of polymeric drug was designed by applying peptides as a specific spacer that linkage with drug was able to be hydrolyzed by peptidases. The immunogenicity of each polymeric drug with CM-chitin was also investigated together with metabolic pathway in mice. CM-chitin was found to be accumulated in bone marrow following to the intravenous injection of ^<14>C or FITC labeled CM-chitin derivatives. But accumulations in bone marrow and spleen were found through oral administration. The strong fluorescent was observed both in macrophages and granulocytes, when FITC-labeled CM-chitin was cultured with bone marrow of mouce. Chitosan porous beads were also applied to concentrate the drug and then controlled release of drug was observed through oral administration into rats. A alginate fiber has also been applied to the carrier of peptide drug for oral administration and an effective release of peptide drug was observed.

本论文研究了水溶性可生物降解的羧甲基甲壳素（CM-chitin）作为药物载体在药物衍生系统中的应用。由于羧甲基甲壳素在钙离子存在下易于吸附苯基药物，并通过与三价铁形成刚性凝胶而包封药物或前药，因此，药物或前药的缓释是通过药物载体在动物体内的溶菌酶水解来实现的。提出了一种两步水解的药物在动物体内的控制释放方法，即利用肽作为特定的间隔基，与药物键合的肽可以被肽酶水解，从而设计出侧链型聚合物药物。还研究了每种与CM-甲壳素聚合的药物的免疫原性以及在小鼠中的代谢途径。发现在静脉内注射14 <14>C或FITC标记的CM-几丁质衍生物后，CM-几丁质在骨髓中积累。但口服给药后发现在骨髓和脾脏中有蓄积。将FITC标记的CM-甲壳素与小鼠骨髓共同培养，在巨噬细胞和粒细胞中均观察到强烈的荧光。采用壳聚糖多孔微球对药物进行浓缩，并通过大鼠口服给药观察药物的控制释放。海藻酸纤维也被应用于口服给药的肽类药物的载体，并观察到肽类药物的有效释放。