CN115531602A - 一种促进胃溃疡愈合的氨基酸水凝胶及其制备方法 - Google Patents
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Abstract
本发明公开了一种促进胃溃疡愈合的氨基酸水凝胶及其制备方法，该氨基酸水凝胶在pH=3‑7条件下制备且用于胃溃疡愈合，效果优于奥美拉唑，其制备方法为：取氨基酸在二甲基亚砜中溶解成溶液，再加入硝酸银溶液，最后加入羟乙基纤维素、丙三醇和Tris‑HCl溶液组成的缓冲溶液进行pH调控，室温下静置即形成不依赖pH成型的氨基酸水凝胶且不易变质。本发明利用三羟基氨基甲烷将Ag+原位还原成AgNPs，避免了使用有机溶剂和有害还原剂，制备方法绿色且重复性好，获得的不依赖pH成型的水凝胶具有优异的抗菌性能和细胞相容性，胃溃疡愈合效果好，可以作为细胞递送载体，在生物医用、无菌处理、伤口敷料等领域具有潜在的应用价值。
Description
技术领域
本发明涉及生物医用材料，属于生物体的伤口敷料技术领域，具体涉及一种促进胃溃疡愈合的氨基酸水凝胶及其制备方法。
技术背景
超分子化学最初由J.M Lehn定义为“超越分子的化学”，泛指利用分子间的非共价键作用形成一维、二维和三维有序结构的一门学科（Matson J.B. and Stupp, S.I.,Self-assembling peptide scaffolds for regenerative medicine[J]. ChemicalCommunication, 2012, 48(1): 26-33. Babu,S.S., Prasanthkumar,S., andAjayaghosh,A
.,Self-Assembled gelators for organic electronics[J]. AngewandteChemie International Edition, 2012, 5l(8): 1766 - 1776.）而分子自组装是超分子化学的重要分支之一。
其中，肽自组装是组装领域最有前景的研究方向之一，因为它们具有内在的自组装能力，能够自组装成其中，肽自组装是组装领域最有前景的研究方向之一，因为它们具有内在的自组装能力，能够自组装成天然的生物结构，例如所有生命系统中的氨基酸和短肽等，作为一类生物材料已经引起了人们的兴趣，因为它们可以提供形成有序结构所需的所有分子信息，这些信息可以在从简单细菌到人类细胞的各种生命形式中找到。
近年来金属-配体相互作用也被用于构建超分子凝胶，将金属中心结合到超分子凝胶中将产生在传统水凝胶中不能实现的多功能水凝胶。天然氨基酸代替传统的合成分子与金属离子配位形成生物配位聚合物（BCPs），有配位作用通过金属离子连接的氨基酸单元组成的BCP在结构上类似于肽链并且被认为是用于“程序化设计”的材料。这种BCP结构的设计和制造将有助于我们利用天然配体的仓库并扩大其备用库。
单个氨基酸是允许Fmoc修饰的最简单的生物分子，越来越多的Fmoc修饰的氨基酸能够自组装，并且其中一些（大部分具有芳族侧链的）能够形成延伸的三维（3-D）结构，捕获溶剂分子并形成凝胶。但是根据现有报道，由氨基酸制备的水凝胶材料通常只能在中性（pH=7.4）环境下制备成功且稳定存在，这制约了我们想在上消化道术后消炎止血的初衷，并制约其发展。
其中，因为纳米银所具有的优异的光谱抗菌性，基于纳米银的水凝胶材料，在生物医学领域发挥这重要的作用，然而，现有报道的纳米银水凝胶材料制备过程繁琐，生物相容性差，讲解困难且分布不均等缺点，制约了纳米银水凝胶材料的广泛应用和发展。
因此，基于以上内容，我们开发了一种含银氨基酸水凝胶材料的方法。本发明方法简单，可重复性好，且解决了在酸性条件下能够实现其功能的目的，在胃溃疡愈合等生物医用领域的应用前景广阔。
发明内容
针对目前存在的技术问题，本发明旨在提供一种能够在酸性条件以及中性条件下基于氨基酸的含纳米银的抗菌水凝胶，其步骤简单，原料廉价易获得，具有普适性，在生物医用材料、无菌处理、体外伤口敷料记忆体内术后伤口处理等方面的用途。本发明的氨基酸自组装水凝胶是通过银离子和芴基氨基酸上的侧链上的基团以金属-配体相互作用的方式而构筑的超分子水凝胶，具有广范围的凝胶环境、良好的生物相容性、优秀的抗菌性能；此外，还能够使得生物体内术后所形成的创面进行保护，达到尽早愈合的目的，减少患者术后疼痛等相关临床症状，更有助于防止术后穿孔、狭窄、出血等并发症的发生。
为了实现上述目的，本发明采用以下技术方案：
一种促进胃溃疡愈合的氨基酸水凝胶的制备方法包括以下步骤：取Fmoc基氨基酸，先用二甲基亚砜溶解成150-200mg/mL溶液，再超声溶解2min，然后加入一定浓度的硝酸银溶液，最后加入羟乙基纤维素（HEC）、丙三醇和Tris-HCl溶液组成的缓冲溶液进行pH值的调控，室温静置3-10min，即得到促进胃溃疡愈合的氨基酸水凝胶。
进一步地，本发明选用的氨基酸是Fmoc-Glu-OMe，Fmoc基氨基酸中含有一个羧基和酰胺键，可以提供两个氢键结合位点，方便其余缓冲溶液中HEC以氢键的方式结合，同时，羧基和酰胺键作为富电子集体，也可以与缺电子基团形成配位键；同时，Fmoc基团的引入，为体系提供了π-π堆积作用，大大增加了分子间作用力。
进一步地，Fmoc-Glu-OMe结构式为
，羟乙基纤维素结构式为
。
进一步地，硝酸银溶液的浓度为4-15mM，优选为8-15mM，加入的硝酸银既可以和芴基氨基酸以配位键的形式组装成水凝胶。
进一步地，缓冲溶液中的配比是1.3wt％丙三醇（作为缓冲液的混合溶剂），5wt％wtHEC，93.7wt％Tris-HCl溶液；pH值为3-7.4，通过缓冲溶液中的HEC和芴氨基酸形成氢键的方式自组装成水凝胶。
有益效果：
（1）本发明基于π-π堆积作用，通过芴基修饰氨基酸小分子，引入银纳米颗粒，制备了不依赖pH（pH=3-7.4）的自组装水凝胶材料。制备方法简单有效。
（2）本发明通过加入三（羟甲基）氨基甲烷（具有一定的还原性），成功的利用三羟基氨基甲烷将Ag+还原成AgNPs，这完全避免了使用有机溶剂和有害的还原剂，完全符合绿色化学的基本原则，因此原料及方法均能够提高自组装水凝胶材料的生物相容性。
（3）本发明制备的水凝胶材料具有高效的抗菌性能（≥ 99.9%）及生物相容好（≥80%），止血及促进胃溃疡愈合的效果优异，有望在促进胃溃疡愈合的消炎抗菌材料、抗菌止血材料、药物缓释材料及其它生物医药等方面有潜在的应用。
附图说明
图1是自组装水凝胶的结构示意图；
图2是水凝胶的数码图片；
图3是水凝胶的红外谱图；
图4是水凝胶的紫外吸收光谱图；
图5是水凝胶的抑菌环实验；
图6是水凝胶胃溃疡治疗效果图。
具体实施方式
本发明公开了一种具有长效抗菌作用的酸性条件下自组装水凝胶（促进胃溃疡愈合的氨基酸水凝胶）的制备方法。制备材料包括：Fmoc-Glu-OMe、硝酸银、二甲基亚砜、三（羟甲基）氨基甲烷、HEC、丙三醇、盐酸、超纯水、生理盐水。
实施案例1：
首先将Fmoc-Glu-OMe（7mg）在DMSO（40µL）进行超声溶解，溶解时间2min，使其能够充分溶解，得到175mg/mL的Fmoc-Glu-OMe溶液；
配置硝酸银溶液，称取4.079mg的硝酸银，然后加入30mL超纯水，超声溶解，待其充分溶解，便能得到8mM的硝酸银储备溶液。
配置缓冲溶液，首先称取一定量的三（羟甲基）氨基甲烷，加入超纯水，超声溶解，得到10mM的三（羟甲基）氨基甲烷储备液，然后以5wt％的占比加入HEC，1.3wt％的占比加入丙三醇，并以盐酸调节pH=3.0。
制备自组装凝胶材料：在Fmoc-Glu-OMe储备溶液中，加入硝酸银储备液（600µL），然后加入缓冲溶液（pH=3.0），最后使用涡旋混合仪使其混合均匀，静置几分钟，便能够得到自组装氨基酸水凝胶，命名为Fmoc-Glu-Ome/Ag/HEC@8，简称F/Ag/H@8，水凝胶自组装结构如图1所示。凝胶如图2所示，倒立放置，样品不流动，为凝胶状态。
实施案例2：
首先将Fmoc-Glu-OMe（7mg）在DMSO（40µL）进行超声溶解，溶解时间2min，使其能够充分溶解，得到175mg/mL的Fmoc-Glu-OMe溶液；
配置硝酸银溶液，称取5.096mg的硝酸银，然后加入30mL超纯水，超声溶解，待其充分溶解，便能得到10mM的硝酸银储备溶液。
配置缓冲溶液，首先称取一定量的三（羟甲基）氨基甲烷，加入超纯水，超声溶解，得到10mM的三（羟甲基）氨基甲烷储备液，然后以5wt％的占比加入HEC，1.3wt％的占比加入丙三醇，并以盐酸调节pH=4.0。
制备自组装凝胶材料：在Fmoc-Glu-OMe储备溶液中，加入硝酸银储备液（600µL），然后加入缓冲溶液（pH=4.0），最后使用涡旋混合仪使其混合均匀，静置几分钟，便能够得到自组装氨基酸水凝胶，命名为Fmoc-Glu-Ome/Ag/HEC@10，简称F/Ag/H@10。水凝胶自组装结构如图1所示。凝胶如图2所示，倒立放置，样品不流动，为凝胶状态。
实施案例3：
首先将Fmoc-Glu-OMe（7mg）在DMSO（40µL）进行超声溶解，溶解时间2min，使其能够充分溶解，得到175mg/mL的Fmoc-Glu-OMe溶液，水凝胶自组装结构如图1所示；
配置硝酸银溶液，称取7.620mg的硝酸银，然后加入30mL超纯水，超声溶解，待其充分溶解，便能得到15mM的硝酸银储备溶液。
配置缓冲溶液，首先称取一定量的三（羟甲基）氨基甲烷，加入超纯水，超声溶解，得到10mM的三（羟甲基）氨基甲烷储备液，然后以5wt％的占比加入HEC，1.3wt％的占比加入丙三醇，并以盐酸调节pH=5.0。
制备自组装凝胶材料：在Fmoc-Glu-OMe储备溶液中，加入硝酸银储备液（600µL），然后加入缓冲溶液（pH=5.0），最后使用涡旋混合仪使其混合均匀，静置几分钟，便能够得到自组装氨基酸水凝胶，命名为Fmoc-Glu-Ome/Ag/HEC@15，简称F/Ag/H@15。水凝胶自组装结构如图1所示。凝胶如图2所示，倒立放置，样品不流动，为凝胶状态；红外谱图如图3所示；紫外光谱谱图如图4所示。
通过抑菌环的方法来评估水凝胶的抗菌性能。准备直径为6 mm的纸片若干，由生理盐水浸泡过后的纸片作为空白对照组，分别由Fmoc-Glu-Ome溶液，Fmoc-Glu-Ome/HEC水凝胶（不包含Ag）、Fmoc-Glu-Ome/Ag/HEC@15水凝胶浸泡过后的纸片作为实验组；将事先处理好的菌液接种在培养皿上之后，并将纸片放置在培养皿中间；随后放置在细菌培养箱中，培养16 h，观察水凝胶的抗菌效果。图5为空白组和不同实验组的抗菌效果图片，经过16 h的培养， Fmoc-Glu-Ome/Ag/HEC@15水凝胶浸泡过后的纸片周围均有明显的抑菌环存在，表现出优异的抗菌性能。
通过胃溃疡伤口模型实验来评估Fmoc-Glu-Ome/Ag/HEC@15水凝胶促进胃溃疡伤口愈合能力。如图6所示为水凝胶治疗胃溃疡9 h、24 h的实验结果，与空白对照组或奥美拉唑相比，Fmoc-Glu-Ome/Ag/HEC@15水凝胶组具有优异的创面愈合功能，对胃黏膜损伤较小，展现了良好的促胃溃疡伤口愈合能力。
以上所述均是本发明的优选实施方式，并不局限本发明保护范围，本技术领域的普通专业人员阅读本发明之后，在没有做出创造性劳动的前提下所获得的所有其它实施实例，都属于本发明保护的范围。
Claims (7)
1.一种促进胃溃疡愈合的氨基酸水凝胶的制备方法，其特征在于，取氨基酸，先用二甲基亚砜溶解到150-200mg/mL溶液，然后超声溶解，再加入硝酸银溶液，随后利用羟乙基纤维素、丙三醇和Tris-HCl溶液组成的缓冲溶液调控pH值，室温静置3-10min，即得到促进胃溃疡愈合的氨基酸水凝胶。
2.根据权利要求1所述的制备方法，其特征在于，所述氨基酸为Fmoc基氨基酸中的一种。
3.根据权利要求1所述的制备方法，其特征在于，硝酸银溶液浓度为8-15mM。
4.根据权利要求1所述的制备方法，其特征在于，超声溶解的时间为2min。
5.根据权利要求1所述的制备方法，其特征在于，pH值为3-7.4。
6.根据权利要求1所述的制备方法，其特征在于，所述缓冲溶液中羟乙基纤维素质量分数为1.3%，丙三醇质量分数为5%，Tris-HCl溶液质量分数为93.7%。
7.一种如权利要求1-6任一项所述的制备方法制得的促进胃溃疡愈合的氨基酸水凝胶。
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2015057170A1 (en) * | 2013-10-18 | 2015-04-23 | Agency For Science, Technology And Research | Nanoparticle-containing hydrogels |
| CN106146862A (zh) * | 2015-03-31 | 2016-11-23 | 中南大学 | 一种抗菌性的超分子杂合水凝胶及其制备方法和应用 |
| CN107625725A (zh) * | 2017-09-08 | 2018-01-26 | 中国科学院过程工程研究所 | 基于氨基酸的含纳米银的抗菌水凝胶及其制备方法和用途 |
| CN108926574A (zh) * | 2018-09-20 | 2018-12-04 | 天津科技大学 | 一种杂化抗菌水凝胶及其制备方法 |
| CN109251325A (zh) * | 2018-09-20 | 2019-01-22 | 天津科技大学 | 一种氨基酸衍生物水凝胶及其制备方法 |
| CN113045774A (zh) * | 2021-04-19 | 2021-06-29 | 江汉大学 | 一种含纳米银的双网络复合水凝胶或水凝胶球及其制备方法和应用 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106146862A (zh) * | 2015-03-31 | 2016-11-23 | 中南大学 | 一种抗菌性的超分子杂合水凝胶及其制备方法和应用 |
| CN107625725A (zh) * | 2017-09-08 | 2018-01-26 | 中国科学院过程工程研究所 | 基于氨基酸的含纳米银的抗菌水凝胶及其制备方法和用途 |
| CN108926574A (zh) * | 2018-09-20 | 2018-12-04 | 天津科技大学 | 一种杂化抗菌水凝胶及其制备方法 |
| CN109251325A (zh) * | 2018-09-20 | 2019-01-22 | 天津科技大学 | 一种氨基酸衍生物水凝胶及其制备方法 |
| CN113045774A (zh) * | 2021-04-19 | 2021-06-29 | 江汉大学 | 一种含纳米银的双网络复合水凝胶或水凝胶球及其制备方法和应用 |
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