本文選題：透明質酸 + 可注射原位形成�。� 參考：《海南大學》2014年碩士論文

【摘要】：透明質酸是一種生物相容、生物可降解的直鏈高分子多糖聚合物。它廣泛分布于人體各部位,并且發(fā)揮著重要的生理作用。本課題研究探索了一種新的、高效的、在溫和條件下通過透明質酸的羥基修飾和功能化透明質酸的方法,并且合成得到了一種半胱氨酸透明質酸結合物。通過修飾透明質酸的羥基,得到通過穩(wěn)定的醚鍵連接的半胱氨酸透明質酸結合物。本課題研究的重大突破是在透明質酸的修飾反應中引入了四丁基氫氧化銨作為助溶劑與催化劑。據查閱文獻結果表明,此方法是一種新的并且第一次應用于多糖的修飾方法中,大大提高了透明質酸的溶解度,并且提高了反應的修飾率,克服了以往修飾透明質酸的過程中溶解度受限,并且反應需要在有機溶劑中進行等一系列導致修飾失敗的問題。 本課題研究所得到的半胱氨酸透明質酸結合物不修飾其結構中的羧基功能團,保留了其具有細胞CD44受體識別能力而通過穩(wěn)定的醚健修飾其羥基得到了具有巰基活性基團的結合物。這些巰基基團可被進一步功能化,將會擴大透明質酸在醫(yī)藥與生物材料領域的應用。 合成得到的半胱氨酸透明質酸結合物可用于制備可注射的原位形成的共價交聯透明質酸水凝膠,延長透明質酸在體內的滯留時間,發(fā)揮更廣泛的作用。 本課題研究運用兩種交聯方法得到了共價交聯的水凝膠：(1)使用半胱氨酸透明質酸結合物與聚乙二醇丙烯酸酯結合物運用邁克爾加成反應得到可注射的原位形成的共價交聯透明質酸水凝膠；(2)使用半胱氨酸透明質酸結合物與不同分支的聚乙二醇硫酯結合物運用自然化學連接反應得到的共價交聯透明質酸水凝膠。通過這兩種方法都能在短時間內獲得水凝膠。水凝膠的形成過程和形成的水凝膠的流變學研究表明,該水凝膠可在十分鐘內形成,并且所形成的水凝膠為共價交聯、具有高度的粘彈性。本研究獲得的水凝膠可注射原位形成,不經過手術而通過針管注射,以最小程度地對機體組織侵入填充任意形狀的缺損,且能與治療藥物混合注射發(fā)揮藥物緩釋作用,預期將可廣泛地應用于外科封閉劑和粘合劑、藥物釋放、組織填充、組織修復和組織工程。
[Abstract]:Hyaluronic acid is a biocompatible, biodegradable polymer with straight chain polysaccharides. It is widely distributed in various parts of the human body and plays an important physiological role. In this paper, a new and efficient method of modification and functionalization of hyaluronic acid by hydroxyl group of hyaluronic acid under mild conditions was studied, and a cysteine hyaluronic acid conjugate was synthesized. By modifying the hydroxyl group of hyaluronic acid, a stable cysteine hyaluronic acid bond was obtained. An important breakthrough in this research is the introduction of tetra ammonium hydroxide as a co-solvent and catalyst in the modification of hyaluronic acid. According to the results of literature review, this method is a new and first time applied to the modification of polysaccharides, which greatly improves the solubility of hyaluronic acid and the modification rate of the reaction. It overcomes a series of problems that lead to the failure of modification, such as the limited solubility in the process of modification of hyaluronic acid and the reaction needs to be carried out in organic solvents. In this study, the cysteine hyaluronic acid conjugate did not modify the carboxyl functional group in its structure. The conjugate with mercapto active group was obtained by modifying its hydroxyl group with stable ether binding. These mercapto groups can be further functionalized, which will expand the application of hyaluronic acid in medicine and biomaterials. The synthesized cysteine hyaluronic acid conjugate can be used in the preparation of injectable covalent crosslinked hyaluronic acid hydrogels, which can prolong the retention time of hyaluronic acid in vivo and play a more extensive role. In this study, two cross-linking methods were used to obtain covalent crosslinked hydrogel: 1) by using cysteine hyaluronic acid conjugate and polyethylene glycol acrylate conjugate, the injectable in situ formation was obtained by Michael addition reaction. The covalent crosslinked hyaluronic acid hydrogels were obtained by using cysteine hyaluronic acid conjugate and polyethylene glycol sulfur ester conjugate with different branches. Hydrogels can be obtained in a short time by both methods. The hydrogel formation process and the rheology of the formed hydrogel show that the hydrogel can be formed in ten minutes and the hydrogel formed is covalent crosslinked with high viscoelasticity. The hydrogel obtained in this study can be injected in situ and injected through needle tube without operation to minimize the invasion of the body tissue to fill any shape defect, and can be combined with the treatment drug injection to play a drug release effect. It is expected to be widely used in surgical sealants and adhesives, drug release, tissue filling, tissue repair and tissue engineering.
【學位授予單位】：海南大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R914.5

【參考文獻】

相關期刊論文 前1條

1 金星,楊春生,宋今詞,翟良全,滕英飛;透明質酸鈉治療膝關節(jié)骨性關節(jié)炎[J];中國骨傷;2000年02期

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本文編號：1824011