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

将水溶性可生物降解的羧甲基甲壳素(CM-甲壳素)作为药物载体应用于药物衍生体系。由于CM-甲壳素在有钙离子存在的情况下容易吸附苯基药物，并通过三价铁与CM-甲壳素形成刚性凝胶来包埋药物或前药，因此前药药物在动物体内的缓释是通过药物载体的溶酶水解实现的。为了实现药物在动物体内的控释，提出了一种两步水解法，即利用多肽作为特定的间隔基，利用多肽酶对药物进行水解，从而设计出悬挂式聚合物药物。同时考察了每种CM-甲壳素聚合物药物在小鼠体内的免疫原性和代谢途径。在静脉注射14&gt；C或FITC标记的CM-甲壳素衍生物后，发现CM-甲壳素在骨髓中积聚。但口服给药可在骨髓和脾组织中发现蓄积。FITC标记的CM-甲壳素与小鼠骨髓共同培养时，巨噬细胞和粒细胞均有较强的荧光。用壳聚糖多孔珠对药物进行浓缩，通过大鼠灌胃给药，观察药物的控释作用。将海藻酸纤维应用于多肽药物载体的口服给药，观察到多肽药物的有效释放。

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.