壳聚糖硫酸酯的制备及其药用价值的研究

IOCAS-IR > 海洋环流与波动重点实验室

	壳聚糖硫酸酯的制备及其药用价值的研究
	严共鸿
学位类型	博士
	1999
学位授予单位	中国科学院海洋研究所
学位授予地点	中国科学院海洋研究所
学位专业	海洋化学
关键词	壳聚糖硫酸酯纯化磺化降血糖增强免疫
摘要	壳聚糖是甲壳质脱去乙酰基的产物，本身可生物降解，具有良好的生物相容性，经过磺化引入硫酸根功能团，改变了其理化性质，授予化合物重要生理功能，具有增强机体免疫力，抑制肿瘤，抑制病毒，降糖，降脂，抗凝血，防治血栓、溃疡和肾衰等方面的作用，国内外对其开发十分活跃。本文对壳聚糖硫酸酯衍生物的制备及生物活性进行了比较系统的研究，通过二种方法制备出二个不同含硫量和分子量的样品，分别进行了急性毒性试验和药效试验，结果表明样品毒副作用小，动物对其具有很大耐受性，小鼠i.g和i.p给药的一日最大耐受量分别大于10g/kg和2.5g/kg。该衍生物具有极显著的降血糖和增强免疫作用；在同等剂量下，对防治血栓和抗凝血有一定作用，但不显著；降胆固醇及甘油三酯效果不明显。作为药用的壳聚糖原料应预处理，纯化后原料分子量在20万-30万道尔顿范围，然后采用ClSO_3H/DMF, ClSO_3H/浓 H_2SO_4磺化方法得到硫酸酯衍生物，其 SO_4~(2-)含量分别为 21.6%， 30.5%，取代度分别为 0.44， 0.68。由 IR、 NMR及无素分析证实壳聚糖分子引入了 SO_4~(2-)，取代位点发生以 C_3和 C_6位点。本文对壳聚糖硫酸酯降糖和增强免疫作用机理进行了探讨。壳聚糖硫酸酯具有天然多糖的非细胞毒性特点，可能通过诱导白介素-I、II，活化B细胞、T细胞和巨噬细胞而增强细胞免疫，促进行液免疫；并通过促进胰岛素分泌，提高胰岛素敏感性，增强葡萄糖的代谢利用，从而降低血糖。研究发现，壳聚糖硫酸酯具有剂量依赖生物活性，随首剂量增加，降糖、增强免疫、降胆固醇和甘油三酯、抗凝血和防治血栓形成的作用都增大，随着分子量减小和磺化程度提高，这些药效作用都有所增强。通过本研究工作确定了壳聚糖磺化衍生物进一步开发成为新药的可能性，对深入开发利用甲壳质资源、促进我国海洋药物的发展具有十分重要的意义。
其他摘要	Chitosan is the N-deacetylated product of chitin, with function of bio-degradation, excellent compatibility, no toxicity, it is particularly fit for medical use. The physical and chemical properties of chitosan are changed through introduction of sulfate group by sulphonation and the compound showed many new important physiological functions, such as: increasing immunity, inhibiting tumor and virus, decreasing blood glucose and blood lipid, anticoagulating, preventing and treating thrombus, ulcer and renal failure. So chitosan has very great developmental prospect and is being actively developed throught the world. We have studied the preparation of chitosan sulfate and its bioactivities systematically. Two samples with different sulfate contents and molecular weights were prepared with two methods. Their acute toxicitic tests showed that the two samples have little side effects, experimental animals have great resistance to them, the maxium tolerances of mice through i.g and i.p administration are 10g/kg.day and 2.5g/kg.day respectively. The pharmacologic tests showed, the two samples have remarkable function of decreasing blood glucose and increasing immunity, and have some effect in preventing and treating thrombus and anticoagulating, no obvious effect on decreasing cholesterol and triglyceride. Chitosan for medical use must have high purity, so the raw materials should be pre-treated. The molecular weight of material after purification is 2.0 * 10~5-3.0 * 10~5 dalton. SO_4~(2-) Contents in derivatives from purified chitosan through ClSO_3H/DMF and ClSO_3H/conc. H_2SO_4 sulfonation methods, are 21.6% and 30.5% respectively, and their degrees of substitution are 0.44 and 0.68 respectively. Results of I. R, NMR and elements analyses showed that chitosan have been introduced with SO_4~(2-) group, substitution took place at the position of C_3, C_6. The mechanism of chitosan sulfate's effect on decreasing blood glucose and promoting immunity are discussed in this paper. With the non-cytotoxicity characteristic of natural polysaccharides, chitosan can enhance cellular-immunity and promote humoral immunity through inducing interleukin I, II and activating B-cell, T-cell and macrophage; can decrease blood glucose through promoting insulin's secretion, improving insulin's sensitivity and enhancing glucose's metabolic use. Chitosan sulfate has dosage-dependent biological activity. The effects of improving immunity, decreasing level of blood glucose, cholestorin and triglyceride, anticoagulating and preventing and treating thrombus can be increased with higher dosage, higher sulfate content and lower molecular weight. Our work on chitosan sulfates is very important to further exploition of chitosan, and promotion of our national marine drugs industry.
页数	43
语种	中文
文献类型	学位论文
条目标识符	http://ir.qdio.ac.cn/handle/337002/1391
专题	海洋环流与波动重点实验室
推荐引用方式 GB/T 7714	严共鸿. 壳聚糖硫酸酯的制备及其药用价值的研究[D]. 中国科学院海洋研究所. 中国科学院海洋研究所,1999.

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