壳寡糖及其新型衍生物的制备和抗肿瘤活性初步研究

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	壳寡糖及其新型衍生物的制备和抗肿瘤活性初步研究
其他题名	The preparation of Oligochitosan and new Derivatives of Oligochitosan and Study the anti-cancer activity
	蔡圣宝
学位类型	博士
	2009-05-19
学位授予单位	中国科学院海洋研究所
学位授予地点	海洋研究所
关键词	壳寡糖制备木瓜蛋白酶壳寡糖衍生物制备抗肿瘤
摘要	壳聚糖具有多种生物活性且无毒、无污染，可生物降解，但分子量大，水溶性差，其应用受到很大限制。壳寡糖具有良好的水溶性，其制备方法和应用近年来成为研究的热点。本论文详细研究了酶法和化学法制备壳寡糖的工艺条件，并对酶降解和化学氧化降解的产物进行了比较，结果表明氧化降解的壳寡糖氨基含量有所下降，而酶法降解的产物氨基含量基本没有变化。研究发现在木瓜蛋白酶中加入Vc可以一定程度上降低降解产物的粘度。对几种酶联合降解效果进行了研究，结果表明三种酶的联合降解可得到分子量为1800左右的壳寡糖产物，同时可获得较高产率。本论文还制备了三种新型壳寡糖衍生物，并研究了壳寡糖和三种衍生物的抗肿瘤活性。通过在壳寡糖上引入胍基乙酸，首次合成了壳寡糖胍基乙酰衍生物(N-2-胍基乙酰-壳寡糖)；引入烟酰氯、烟酰异硫氰酸酯合成了(N-2-烟酰-壳寡糖、N-2-烟酰异硫氰酸酯-壳寡糖)。通过对BEL•7402肝癌细胞进行了抑制肿瘤活性研究表明：烟酰壳寡糖衍生物的抗肿瘤活性较其他两种衍生物和壳寡糖的活性要好(1mg/ml浓度下抑制率为21.54%)，在较低浓度下有一定的抑制活性（50ug/ml浓度下抑制率为3.57%）。随着浓度的升高，抑制活性也随之提高。烟酰异硫氰酸酯壳寡糖衍生物和胍基乙酰壳寡糖衍生物在低浓度条件下对肿瘤细胞基本没有抑制活性，在高浓度条件下有一定的抑制活性。
其他摘要	Chitosan is a kind of natural polysaccharide, which is reproducible and it has non-toxicity, good biocompatibility and biodegradability; it has many bioactivities. Because of its high molecular weight, it has poor-solubility which limited its use. The preparation methods and applications of oligochitosan which has good-solubility have received considerable interests. In this paper, we study the technic condition of the enzyme method and the chemical method in detail. And we compared the products prepared by this two method. And found that the amino contents of the products prepared by chemical method were lower than that of the material. The amino contents of the products prepared by enzyme method almost had no change. Through the study, we found that it could reduce the viscosity of the depolymerization product when added Vc into the depolymerization system. And then we research the enzyme-depolymerziation by several enzymes. It could get oligochitosan whose molecular weight is about 1800 by using three enzymes. And the product yield is also high. Three new kinds of oligochitosan derivatives, clycocyamine derivative of oligochitosan, nicotinoyl derivative of oligochitosan, nicotinoyl isothiocyanates derivative of oligochitosan, were obtained. The inhibition effects of the derivatives on BEL•7402 of liver cancer were studied. The results showed that nicotinoyl derivative of oligochitosan had a better anti-cancer activity than that of other two derivatives and the oligochitosan (inhibitory ratio is 21.54% at 1mg/mL). It has anti-cancer activity at low concentration (inhibitory ratio is 3.57% at 50ug/mL). And the anti-cancer activity depended on derivative concentration. The clycocyamine derivative and nicotinoyl isothiocyanates derivative had no anti-cancer activity at low concentration. But at high concentration, they also had anti-cancer activity.
页数	61
语种	中文
文献类型	学位论文
条目标识符	http://ir.qdio.ac.cn/handle/337002/791
专题	海洋环流与波动重点实验室
推荐引用方式 GB/T 7714	蔡圣宝. 壳寡糖及其新型衍生物的制备和抗肿瘤活性初步研究[D]. 海洋研究所. 中国科学院海洋研究所,2009.

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