论文总字数：23997字

摘 要

研究发现，当生物体机体出现不能被细胞中的抗氧化剂中和的活性氧自由基(ROS)水平升高的情况时，将会导致慢性氧化应激，从而引起如炎症等多种疾病。极大可能会破坏细胞稳态平衡以及细胞组分，包括膜质，蛋白质和DNA。因此探索如何构建活性氧自由基响应的抗炎载药水凝胶具有非同寻常的意义。在炎症部位高水平的ROS作用下，一方面ROS响应水凝胶会受ROS触发实验抗炎药物的定点释放，另一方面ROS响应水凝胶在做出响应行为的同时会消耗炎症部位的ROS，达到协同抑制炎症反应的目的。

本次实验主要探索ROS响应水凝胶的构建方法及其成胶机理：通过酰胺化反应，加入羧基活化剂（等摩尔比的EDC·HCL与NHS），将多巴胺接枝到透明质酸钠上，形成活性氧自由基响应水凝胶的成胶前体化合物，即多巴胺修饰的透明质酸钠（简称HA-DA）。并通过偶联反应，将4-溴甲苯硼酸偶联至四甲基丙二胺的两端，得到另一个成胶前体化合物，即两端为苯硼酸基团的连接分子（简称TSPBA）。将两个成胶前体的水溶液混合,利用TSPBA的苯硼酸基团与HA-DA上多巴胺的邻位酚羟基形成动态共价苯硼酸酯键，构建以动态共价苯硼酸酯键为交联位点的透明质酸三维网络体系。由于动态共价苯硼酸酯键能够在ROS促发下解离，破坏透明质酸三维网络体系，因此所制得的水凝胶为活性氧自由基响应的水凝胶。实验中利用核磁共振氢谱（¹HNMR）表征两个成胶前体化合物的结构。同时通过考察不同多巴胺修饰度的透明质酸钠(23%、24%和27%)对水凝胶成胶的影响。通过调整pH值和2个成胶前体物的浓度以及配比，优化水凝胶的成胶条件。当所采用的HA-DA修饰度越高， pH值越大，成胶时间越快且具有自愈合特性。

关键词：透明质酸；活性氧响应；炎症；水凝胶

Study on Preparation of Active Oxygen Radical Response Hydrogel

Abstract

Studies have found that when the organism of the antioxidants in the body appear cannot be cells and active oxygen free radicals (ROS) levels, will lead to chronic oxidative stress, leading to a variety of diseases such as inflammation.It is highly likely to disrupt the homeostasis of cells and their components, including membranes, proteins and DNA.Therefore, it is of great significance to explore how to construct anti - inflammatory potion gel with reactive oxygen species.In the role of inflammation place a high level of ROS, on the one hand, ROS response hydrogels by ROS fixed-point release trigger experimental anti-inflammatory drugs, on the other hand, ROS response hydrogels in the responsive behavior of inflammation at the same time consumes part of ROS, achieve the goal of synergistic inhibition of inflammation reaction.

This experiment is mainly to explore the way to construct ROS response hydrogels and the gelling mechanism: by amidation reaction, join the carboxyl activator (such as mole ratio of EDC · HCL and NHS), the dopamine grafted onto hyaluronic acid sodium, the formation of active oxygen free radical response hydrogels gel precursor compounds, namely the dopamine modified sodium hyaluronate (HA - DA).By coupling reaction, 4-bromotoluene boric acid was conjugated to both ends of tetramethylalandiamine to obtain another precursors of gelatinization, namely the connecting molecules (TSPBA for short) with benzene borate group at both ends.Mix two gel precursor solution, using TSPBA phenylboronic acid group and HA - DA dopamine ortho phenolic hydroxyl forming dynamic covalent benzene boric acid ester bond, build dynamic covalent benzene boric acid ester bond as crosslinking sites of hyaluronic acid three-dimensional network system.Due to dynamic covalent benzene boric acid ester bond can disintegrate under conscious and ROS, destroy the hyaluronic acid three-dimensional network system, so hydrogel was prepared by reactive oxygen free radical response experiment of water gel using nuclear magnetic resonance hydrogen spectrum (1 HNMR) characterization of the structure of the two gel precursor compound.The effects of sodium hyaluronate (23%, 24% and 27%) with different dopamine modifications on hydrogels were also investigated.The gelation conditions of hydrogels were optimized by adjusting pH value, concentration and ratio of two precursors.The higher the HA-DA modification, the higher the pH value, the faster the gelatinization time and the self-healing property.

Keywords: Hyaluronic acid; Active oxygen response; Inflammation; Hydrogel

目 录

中文摘要 I

Abstract II

第一章引言 1

1.1活性氧自由基响应材料的研究价值 1

1.2各种类型的活性氧响应材料 1

1.2.1 含硫醚聚合物 1

1.2.2 含硒聚合物 3

1.2.3含碲聚合物 3

1.2.4聚（硫缩酮） 4

1.2.5苯基硼酸/苯基硼酸酯聚合物 4

1.2.6用于ROS响应药物释放的水凝胶 5

1.3水凝胶的研究现状 5

1.3.1水凝胶响应材料的背景 5

1.3.2ROS响应的透明质酸（HA）水凝胶的发展 6

第二章 实验部分 8

2.1实验依据 8

2.2实验准备 9

2.2.1实验试剂 9

2.2.2实验仪器 10

2.3实验过程 10

2.3.1透明质酸钠的纯化和降解 10

2.3.2多巴胺修饰的透明质酸（HA-DA）的合成 10

2.3.3两端为苯硼酸基团的连接分子（TSPBA）的合成 11

2.3.4活性氧自由基响应水凝胶的合成 12

2.4结果分析 13

2.4.1透明质酸钠的纯化结果分析 13

2.4.2不同配比的透明质酸钠的接枝率分析 14

2.4.3TSPBA的核磁谱图分析 16

2.4.4水凝胶成胶原理及其自愈合 16

第三章 实验结论 18

参考文献 19

致 谢 23

第一章引言

1.1 活性氧自由基响应材料的研究价值

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