论文总字数：18772字

摘 要

壳聚糖（NSC），因为它本身独特的降解性和抗菌、无毒以及生物相容性和无免疫原性等性质而被广泛在医药等领域应用。壳聚糖的本身是甲壳素的一种高脱乙酰化产物。而甲壳素需要的来源有蟹、虾的壳，这也表明其来源广泛，也正是因他来源广泛，所以多被选择使用，而成为一种广受重视的材料，被重视程度只低于蛋白质骨胶。如今，NSC及其衍生物已经广泛应用于很多产品领域，如，组织工程支架，创伤敷料，以及药物载体等相关领域。例如它早己以微囊（球）等形式在其他领域得到应用。总之，他的各项优点及特殊性造就了今天他被使用的宽广性，形式的广泛性。也是本实验的绝佳选择。

蛇床子素（OST）——中药蛇床子的主要活性成分。有具体的研究表明，在OST所有广泛的药理作用中，抗骨质疏松这一项是极其重要的一项。其作用机制是OST体外可刺激成骨细胞增殖、分化及成熟，刺激新骨形成，可能是一种潜在的蛋白同化制剂。然而OST具有难溶于水和吸收性差的缺点，再加上血流量低、骨组织硬度大、渗透性差，于是更难以顺利到达骨基质。针对此限定，为了在骨的组织中到达有效的治疗浓度，OST通常使用时需全身给药，但这一措施不但降低了OST的药物治疗指数，而且对非骨组织也产生了一些不必要的毒副作用，因此限定了OST在骨质疏松症防治中的临床转化应用。

本研究利用NSC在药物载体领域的功能，通过对其进行结构修饰得到衍生物的方法，形成两亲性聚合物胶束。再通过物理包埋蛇床子素，可提高蛇床子素的相应溶解度以及提高它的相对稳定性，从而提高药物OST的利用程度。从另一方面来说，也相当于想方法对OST进行化学的合成，将其与亲骨性的壳聚糖衍生物相连，合成具有骨靶向性的反应物，增加OST得有效治疗浓度，从而取得更好的最佳的临床疗效。

关键词：壳聚糖；蛇床子素；结构修饰；骨质疏松症；衍生物

The chemical modification of KJT

Abstract

Chitosan (NSC) has been widely used in the fields of medicine because of its unique properties, such as its own degradation and antibacterial, non-toxic, biocompatibility and non immunogenicity. Chitosan is a kind of high deacetylation product of chitin. And chitin from shrimp and crab shell, which also shows the source widely, is because of his extensive sources, so many were choose to use, and become a wide attention of the material, is the degree of attention just below the level of bone glue protein. Today, NSC and its derivatives have been widely used in many product areas, such as tissue engineering scaffold, wound dressing, drug carrier and other related fields. For example, it has been in the form of microcapsules (balls) in other areas to be applied. In a word, his various advantages and special characteristics make him widely used today. Is also an excellent choice for this experiment.

Osthole (OST) - the main active ingredients of Fructus cnidii. Specific studies have indicated that, in all of the pharmacological actions of OST, this one is a very important one. The mechanism is that OST can stimulate the proliferation, differentiation and maturation of osteoblasts in vitro, and stimulate the formation of new bone, which may be a potential protein assimilation agent. However OST has hardly soluble in water and the absorption of the shortcomings of, and blood flow is low, bone tissue hardness, penetration is poor, so more difficult to successfully reach the bone matrix. In this limit, in order to get the effective therapeutic concentration in bone tissue, OST commonly used to systemic administration, but this measure not only reduces the OST therapeutic index, and also produced some unwanted side effects of bone tissue and therefore limit the OST in osteoporosis prevention translational clinical application.

In this study, we use NSC to function in the field of drug carrier, and get the method of its structure modification to get the derivative of the function, and the formation of the two amphiphilic polymer micelle. By physical entrapment of Osthol

can improve osthole corresponding solubility and improve its relative stability, so as to improve the degree of the use of drug OST. From on the other hand, equivalent to the OST for chemical synthesis, and connects it with the pro bony chitosan derivatives, synthesis of bone target to the reactants, increase OST effective therapeutic concentration, so as to achieve better the best clinical curative effect.

Key words: chitosan; Osthol; structure modification; osteoporosis; derivatives

目 录

摘要 I

Abstract II

第一章 文献综述 1

1.1 骨质疏松症的现状 1

1.2 骨质疏松症的简介 1

1.2.1 骨质疏松的病因 2

1.2.2 骨质疏松的症状 3

1.2.3 骨质疏松症的危害 3

1.3 骨质疏松症的相关治疗 3

1.3.1 基础措施 3

1.3.2 药物干预 4

1.3.3 外科治疗 5

1.3.4 预防措施 5

1.4 蛇床子素的相关简介 6

1.4.1 蛇床子素的介绍 6

1.4.2 蛇床子素的作用机制 6

1.4.3 蛇床子素的局限性 7

1.5 壳聚糖的相关介绍 7

1.5.1 壳聚糖简介 7

1.5.2 壳聚糖的相关应用 8

1.6 本课题的主要研究内容 8

1.6.1 本课题的研究目标 8

1.6.2 本课题的研究方法 9

第二章 壳聚糖衍生物的合成 10

2.1 实验原料和器材 10

2.1.1 实验仪器 10

2.1.2 实验原料 10

2.2 壳聚糖衍生物的合成步骤 11

2.2.1还原亚胺反应 11

2.2.2上载磺酰基 11

2.3蛇床子素/壳聚糖衍生物（NOSC-OST）胶束的合成 12

第三章 化合物结构确证 14

3.1 红外分析 14

3.2 ¹H NMR图谱 14

3.3 ¹³C NMR 图谱 15

3.4 壳聚糖衍生物的X衍射分析 16

3.5壳聚糖衍生物热重分析 16

第四章 实验结论与展望 18

4.1实验结论 18

4.2 展望 18

参考文献 19

致 谢 21

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