论文总字数：24523字

摘 要

水凝胶作为生物医药高分子材料领域蒸蒸日上的新兴材料，由于其良好的生物相容性、可注射性、可精确控制形状、适宜的降解性以及对人体无害等优势，在形形色色的医用材料中占有着重要一隅之地。其中又以作为人体局部药物递送的材料受到研究人员的特别关注，本课题的目的是设计合成出一类能在人体患病部位对环境变换进行响应的智能水凝胶，基于我们前期关于AF127/HA-ADH/O-HA-DOP水凝胶的工作，尝试通过将HA-ADH换成含双硫键的小分子交联剂，在交联成胶的同时赋予它氧化还原、pH和温度多重响应性，然后评价它的多重响应性，具体研究氧化还原、pH和温度响应性能的影响因素和控制规律。

本课题设计构建的水凝胶原料是嵌段共聚物聚氧乙烯-聚氧丙烯-聚氧乙烯（PEO-PPO-PEO）、透明质酸和小分子交联剂（3,3'-二硫代双（丙酰肼）），水凝胶成胶原理基于Pluronic^®F127水溶液体系的胶束化和凝胶化以及酰腙键的作用，得到具有氧化还原、pH和温度多重响应性能的水凝胶材料。通过对Pluronic^®F127进行醛基功能化修饰以及透明质酸的氧化，为其与小分子交联剂进行动态共价键交联提供了位点；通过Pluronic^®F127水溶液体系的胶束化，为水凝胶体系提供规整的疏水区，也将醛基位点曝露于胶束的外部；结合动态共价键交联、胶束化作用和疏水作用，酰腙键的形成，以及含二硫键小分子交联剂“3,3'-二硫代双（丙酰肼）”的引入，同时赋予了水凝胶氧化还原、pH和温度响应的特性，实现了水凝胶的温和成胶和多重响应性构筑的双重目标。

关键词：水凝胶 多重响应性 小分子交联剂 酰腙键

Preparation and properties of redox, pH and temperature multiple responsive hydrogels

Abstract

As a new material in the field of biomedical polymer materials, hydrogels are widely used in medical materials due to their advantages of good biocompatibility, injectable, precise shape control, suitable degradability and harmless to human body. Occupies an important place. Among them, it is particularly concerned by researchers as a material for drug delivery. The purpose of this topic is to design and synthesize a type of smart hydrogel that can respond to environmental changes in the diseased part of the human body, based on our previous work on the AF127/HA-ADH/O-HA-DOP hydrogel, we tried to replace HA-ADH with a small molecule cross-linking agent containing disulfide bonds and give it a redox, pH and temperature multiple responsiveness, and then evaluate its multiple responsiveness, specifically study the influencing factors and control laws of redox, pH and temperature response performance.

The hydrogel materials designed and constructed in this project are block copolymer (PEO-PPO-PEO), hyaluronic acid and small molecule cross-linking agent (3,3'-dithiobis(propionohydrazide)), the principle of hydrogel formation is based on the micelle and gelation of the Pluronic^® F127 aqueous solution system and the role of the acylhydrazone bond, resulting in a hydrogel with multiple response properties of redox, pH and temperature。 Hydrogel material by functionally modifying the aldehyde group of Pluronic^® F127 and oxidizing hyaluronic acid, it provides sites for dynamic covalent bond crosslinking with small molecule crosslinking agents; by micelle of the Pluronic^® F127 aqueous solution system, The hydrogel system provides a regular hydrophobic area and also exposes the aldehyde site to the outside of the micelle; combining dynamic covalent bond crosslinking, micelle and hydrophobicity, acylhydrazone bond formation, and disulfide-containing bonds The introduction of the small molecule cross-linking agent "3,3'-dithiobis(propionohydrazide)" at the same time endows the hydrogel with redox, pH and temperature response characteristics, achieving a gentle gel formation and The dual goal of multiple responsive construction.

Key words: Hydrogels ；Multiple responsiveness ；Cross-linking agent of molecule ；Acylhydrazone bond.

目录

摘 要 I

Abstract II

第一章 绪论 １

1.1前言 １

1.2环境响应性水凝胶的研究现状 １

1.2.1pH响应性水凝胶 ２

1.2.2温敏性水凝胶 ２

1.2.3光响应性水凝胶 ３

1.2.4氧化还原响应性水凝胶 ３

1.2.5酶响应性水凝胶 ４

1.2.6电场响应性水凝胶 ４

1.3构筑环境响应性水凝胶的常用策略 ４

1.3.1基于丙烯酸类的pH敏感性水凝胶 ５

1.3.2基于聚（N-异丙基丙烯酰胺）的温敏性水凝胶 ５

1.3.3基于丙烯酰胺类的pH敏感性水凝胶 ５

1.3.4基于席夫碱反应交联的智能水凝胶 ６

1.3.5基于二硫键的pH自愈性水凝胶 ６

1.4当前研究存在的优点和不足 ６

1.4.1优点 ６

1.4.2缺点 ６

1.5本文的研究内容 ７

第二章 多重响应性水凝胶的构建 ８

2.1引言 ８

2.2 实验药品及仪器部分 ９

2.2.1实验药品 ９

2.2.2实验仪器 ９

2.3实验过程部分 ９

2.3.1O-HA的制备 ９

2.3.2O-HA-DOP的制备 １０

2.3.3AF127的制备 １１

2.3.4HA-ADH的制备 １１

2.3.5合成物的结构表征 １２

2.3.6水凝胶的制备 １２

2.3.7水凝胶成胶时间的测定 １３

2.3.8冻干水凝胶的扫描电镜（SEM）形貌表征 １３

2.3.9水凝胶流变性能测试 １４

第三章 结果与讨论 １５

3.1水凝胶前驱体的表征 １５

3.1.1醛基与邻苯二酚基团双功能化的透明质酸衍生物（O-HA-DOP）的表征 １５

3.1.2酰肼化的透明质酸衍生物（HA-ADH）的表征 １６

3.1.3醛基封端的Pluronic®三嵌段聚合物（AF127）的表征 １７

3.2水凝胶的制备与分析 １８

3.2.1水凝胶的制备 １８

3.2.2水凝胶的成胶时间测定 １８

3.2.3水凝胶的微观表征 １９

3.2.4流变性能的讨论 ２０

第四章 结论与展望 ２２

4.1结论 ２２

4.2展望 ２３

参考文献 ２４

致谢 ２７

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