CN114736398B - 一种铜纳米粒子-丁香油双层抑菌水凝胶及其制备方法 - Google Patents
一种铜纳米粒子-丁香油双层抑菌水凝胶及其制备方法 Download PDFInfo
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- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
本发明还公开了一种铜纳米粒子‑丁香油双层抑菌水凝胶及其制备方法,该水凝胶为双层水凝胶,双层水凝胶在形貌结构、性质、性能方面有极大的改善。相比单层CuNPs/PVA、Oil/PVA/PEG水凝胶,双层CuNPs‑Oil/PVA/PEG水凝胶的整体抑菌性、机械性能得到了显著提升。制备的双层CuNPs‑Oil/PVA/PEG水凝胶,具有较强抑菌能力的上层与皮肤直接接触,可解决细胞毒性、生物不相容性等问题。下层用于促进上皮组织的生长,吸收伤口渗出物,具有优异的生物相容性,在抑制抑菌生长的同时促进伤口愈合。上层具有抗氧化性的丁香油向下层渗透,可缓解CuNPs的氧化,提高水凝胶下层的抑菌性及稳定性。
Description
技术领域
本发明属于水凝胶技术领域,具体涉及一种铜纳米粒子-丁香油双层抑菌水凝胶及其制备方法。
背景技术
皮肤创伤作为最常见的创伤之一,极易发生细菌感染,导致伤口愈合延迟和严重的组织损伤。用伤口敷料覆盖受损皮肤是防止细菌入侵最普遍的方法之一。在医学领域中,伤口敷料是护理伤口、避免感染和促进伤口愈合的重要医用物品。一些传统的敷料,如绷带、纱布等,在涂覆抗菌感染的药物之后作用于伤口,会起到防止体液渗漏和保护伤口感染的作用。经研究,伤口环境的变化会影响伤口愈合的速度,湿润和一定温度会加速伤口的愈合。随着社会节奏的加快,越来越多的人经受着不同程度的皮肤创伤,如糖尿病患者手术、慢性伤口等。开发具有特定功能的伤口敷料具有重要的实践价值及理论意义。
对于传统的伤口敷料现阶段还是存在一些不足,如缺乏生物活性和生物降解性、潜在的过敏性、清洗更换不方便等,因此不能完全满足临床需要。理想的皮肤创面敷料应具有保护创面不受微生物感染、有效促进伤口愈合、保湿和吸收伤口渗出物的能力。水凝胶敷料是实现这一目的的最佳选择之一,因为它们能够保持伤口床的清洁,并提供适当的水分和对伤口愈合的抗菌作用。然而,抗菌水凝胶通常包含抗生素或其他抑菌剂,这可能带来一些潜在的副作用,如细菌耐药性、细胞毒性,对于伤口的愈合有阻碍作用。
在此基础上,避免细菌侵入引起的伤口感染是愈合过程中的一个重要问题,抗菌水凝胶具有高吸水性和结构多样性,为对抗细菌感染提供了新的可能性。抗菌水凝胶通常包含抗生素以防止细菌感染,然而,由于抗生素的过度使用和误用,抗生素耐药性的发展已经加剧,迫使细菌产生逃避药物致命作用的机制。其他抗菌水凝胶将杀菌剂纳入水凝胶网络,包括银纳米颗粒,这可能导致细胞毒性。此外,抗菌水凝胶太强的抑菌性对于伤口的愈合有阻碍作用。因此,含有杀菌剂的水凝胶的生物相容性和适当强度的抑菌性是一个主要问题。
发明内容
本发明的目的在于克服上述现有技术的缺点,提供一种铜纳米粒子-丁香油双层抑菌水凝胶及其制备方法,以解决现有技术中含有杀菌剂的水凝胶生物相容性和抑菌性难以结合的问题。
为达到上述目的,本发明采用以下技术方案予以实现:
一种铜纳米粒子-丁香油双层抑菌水凝胶的制备方法,包括以下步骤:
步骤1,在水中混合硫酸铜和十六烷基四甲基溴化铵,超声溶解后,加热,滴加氨水生成铜氨络合物;将抗坏血酸溶液和环糊精溶液加入至铜氨络合物中,制备得到片状铜纳米粒子;
步骤2,将片状铜纳米粒子加入到聚乙烯醇溶液中,均匀搅拌后的冷冻结冰得到双层抑菌水凝胶的下层;
步骤3,重新制备聚乙烯醇溶液,将重新制备的聚乙烯醇溶液和聚乙二醇混合,然后加入丁香油,得到溶胶;将得到的溶胶倒在双层抑菌水凝胶的下层上,形成过程产物,将过程产物冻融后,得到双层水凝胶。
本发明的进一步改进在于:
优选的,步骤1中,硫酸铜和十六烷基四甲基溴化铵的混合质量比为:0.4:(0.1~0.5)。
优选的,步骤1中,加热温度为85~90℃。
优选的,步骤1中,滴加的氨水和硫酸铜的比例为(50-300)μL:0.4g。
优选的,步骤1中,抗坏血酸溶液的浓度为(0.8~1.5)g/25mL,环糊精溶液的浓度为(0.1~0.4)g/25mL。
优选的,步骤2中,片状铜纳米粒子和聚乙烯醇溶液的混合比例为0.155g:15mL。
优选的,步骤3中,重新制备的聚乙烯醇溶液浓度为2g/15mL,聚乙烯醇和聚乙二醇的混合质量比为2:(0.2-1)。
优选的,步骤3中,重新制备的聚乙烯醇溶液在85-90℃下搅拌均匀。
优选的,步骤3中,加入的丁香油和聚乙烯醇溶液的体积比为1:15。
一种通过上述任意一项所述制备方法制得的铜纳米粒子-丁香油双层抑菌水凝胶,所述双层抑菌水凝胶中,下层为掺杂有片状铜纳米粒子的聚乙烯醇水凝胶,上层为包含丁香精油的聚乙烯醇/聚乙二醇水凝胶。
与现有技术相比,本发明具有以下有益效果:
本发明公开了一种铜纳米粒子-丁香油双层抑菌水凝胶的制备方法,该制备方法首先在制备过程中通过硫酸铜和氨水制备出铜氨络合物,通过抗坏血血酸将铜氨络合物中的Cu2+还原为CuNPs,环糊精能够保护CuNPs不被迅速氧化,制备过程中加入的十六烷基四甲基溴化铵能够使得制备出的CuNPs不是粒子状,而是片状;片状铜纳米粒子相对于常规颗粒状的铜纳米粒子粒径更小,体积更小,且在后续的应用过程中不易聚集。上层水凝胶的制备过程中加入了丁香油,强化整个凝胶的抑菌性能。同时因为上层的丁香油能够不断的向下层的PVA中渗透,使得丁香油能够遏制片状铜纳米粒子被氧化,延长片状的铜纳米粒子的使用寿命,有效促进伤口的愈合,同时丁香油向下渗透增强了整个双层水凝胶的抑菌性能。
本发明还公开了一种铜纳米粒子-丁香油双层抑菌水凝胶,该水凝胶为双层水凝胶,双层水凝胶在形貌结构、性质、性能方面有极大的改善。相比单层CuNPs/PVA、Oil/PVA/PEG水凝胶,双层CuNPs-Oil/PVA/PEG水凝胶的整体抑菌性、机械性能得到了显著提升。制备的双层CuNPs-Oil/PVA/PEG水凝胶,具有较强抑菌能力的上层与皮肤直接接触,可解决细胞毒性、生物不相容性等问题。下层用于促进上皮组织的生长,吸收伤口渗出物,具有优异的生物相容性,在抑制抑菌生长的同时促进伤口愈合。上层具有抗氧化性的丁香油向下层渗透,可缓解CuNPs的氧化,提高水凝胶下层的抑菌性及稳定性。双层水凝胶中的下层用于促进上皮组织的生长,吸收伤口渗出物,具有优异的生物相容性,上层设计用于防止微生物感染,具有强抑菌性,可避免与皮肤直接接触。该水凝胶材料具有应用于伤口敷料领域的潜力。
附图说明
图1为CuNPs-Oil/PVA/PEG水凝胶在制备过程中各阶段产物的SEM对比图;
(a)图和(b)图是PVA的扫描电镜图,(c)图和(d)图是添加了CuNPs的CuNPs/PVA水凝胶的表面形貌图,(e)图和(f)图显示了PVA/PEG水凝胶的多孔表面,(g)图和(h)图显示了Oil/PVA/PEG水凝胶的表面形貌,(i)图、(j)图和(k)图是双层CuNPs-Oil/PVA水凝胶的断面图。
图2为CuNPs-Oil/PVA/PEG水凝胶在制备过程中各阶段产物的红外图;
图3为CuNPs粉末的XRD图;
图4为CuNPs-Oil/PVA/PEG水凝胶在制备过程中各阶段产物的溶胀曲线(a)和应力-应变曲线(b)。
图5为CuNPs(a)-(d)、EO(e)-(l)不同添加量对双层水凝胶抑菌性的影响
图6为CuNPs-Oil/PVA/PEG水凝胶在制备过程中各阶段产物的抑菌性(a)-(f)以及CuNPs-Oil/PVA/PEG双层水凝胶的上、下层抑菌耐久性(g)-(l)。
具体实施方式
下面结合附图和具体的实施例对本发明做进一步详细描述:
本发明的一个实施例公开了一种CuNPs-Oil/PVA/PEG双层抑菌水凝胶的制备方法,具体包括以下步骤:
步骤一,片状CuNPs的合成
首先,在25mL去离子水中加入0.4g硫酸铜和0.1~0.5g的十六烷基三甲基溴化铵,优选的,十六烷基三甲基溴化铵作为即将合成的片状CuNPs的分散剂,使用量最优的为0.4g,超声溶解,加热到85~90℃,滴加50-300μL氨水生成铜氨络合物;十六烷基三甲基溴化铵均匀的分散在溶液中。
以水作为溶剂,分别配置浓度为(0.8~1.5)g/25mL的抗坏血酸水溶液和浓度为(0.1~0.4)g/25mL的环糊精水溶液;优选的,抗坏血酸溶液的浓度为1.1g/25mL,环糊精溶液的浓度为0.25g/25mL。
将抗坏血酸溶液和环糊精溶液快速加入至铜氨络合物中,三者的体积比为1:1:1。溶液颜色由蓝色变为暗黄色,最终生成红棕色沉淀,搅拌5min后,离心得到片状铜纳米粒子,简写为CuNPs。
该过程中抗坏血酸可将铜氨络合物中的Cu2+还原为CuNPs,环糊精能够保护CuNPs不被迅速氧化,制备出的铜纳米粒子为片状。片状铜纳米粒子相对于常规颗粒状的铜纳米粒子粒径更小,体积更小,且在后续的应用过程中不易聚集。
步骤2,CuNPs-Oil/PVA/PEG双层抑菌水凝胶的制备
将0.15g的片状铜纳米粒子加入到15mL聚乙烯醇(PVA)溶液中,搅拌均匀后倒入六孔培养皿中在0℃冷冻结冰,即为双层抑菌水凝胶的下层。其中聚乙烯醇溶液为聚乙烯醇和水按照2g:15mL混合的溶液,聚乙烯醇溶液能够使加入铜纳米粒子生成的溶液体积更小;
将2g聚乙烯醇PVA加入15mL水中,在85~90℃下搅拌溶解均匀,加入(0.2-1)g的聚乙二醇(PEG),然后缓慢滴加1mL丁香油溶解;聚乙二醇能够溶解丁香油,优选的,加入的聚乙二醇的质量为0.4g,得到溶胶。将得到的溶胶倒在冻好的下层铜纳米粒子水凝胶上,即为上层,形成过程产物,将过程产物冻融循环3~5次,得到双层水凝胶。双层的水凝胶厚度为1~3mm。
最终形成的双层水凝胶中,下层为掺杂有片状铜纳米粒子的聚乙烯醇水凝胶,上层为包含丁香精油的聚乙烯醇/聚乙二醇水凝胶。
下面结合具体实施例对本发明进一步的描述。
实施例1
步骤一,片状CuNPs的合成:首先,在25mL去离子水中加入0.4g硫酸铜和0.4g十六烷基三甲基溴化铵,超声溶解,加热到85℃,滴加150μL氨水生成铜氨络合物,将配置好的1.1g/25mL抗坏血酸、0.25g/25mL环糊精溶液快速加入,抗坏血酸可将Cu2+还原为CuNPs,环糊精能够保护CuNPs不被迅速氧化。溶液颜色由蓝色变为暗黄色,最终生成红棕色沉淀,搅拌5分钟。离心得到片状铜纳米粒子。
步骤2,CuNPs-Oil/PVA/PEG双层抑菌水凝胶的制备:将合成的铜纳米粒子溶液2.5mL加入到溶解的聚乙烯醇(PVA)中,搅拌均匀。倒入六孔培养皿中冷冻结冰,即为下层。2g PVA加入15mL水中,85℃下搅拌溶解15min,加入0.4g聚乙二醇(PEG),缓慢滴加1mL丁香油溶解。将得到的溶胶倒在冻好的下层铜纳米粒子水凝胶上,即为上层。将其冻融循环3次,得到双层水凝胶。
(1)SEM分析
图1为CuNPs-Oil/PVA/PEG水凝胶在制备过程中各阶段产物的SEM对比图。图1中(a)图和(b)图是PVA的扫描电镜图,图中可以显示出PVA致密的表面形貌。经反复冻融制备的PVA水凝胶,在冷冻干燥的过程中,低温使水凝胶进一步交联,且冰慢慢融化,水凝胶的孔隙结构渐渐塌陷变得致密。图1中(c)图和(d)图是添加了CuNPs的CuNPs/PVA水凝胶的表面形貌。可以看到片状CuNPs的加入使PVA表面变得凹凸不平,片状CuNPs在与PVA溶胶混合过程中进一步碎裂成更小的不规则粒子,且CuNPs均匀地分散在PVA中。经测量PVA水凝胶中CuNPs的粒径大约为280nm。图1(e)(f)显示了PVA/PEG水凝胶的多孔表面,由于加入的PEG具有制孔作用。图1(g)和(h)显示了Oil/PVA/PEG水凝胶的表面形貌,Oil的加入填补了原有的孔洞,且小油滴均匀分散在水凝胶中,表明丁香油溶解完全。图1(i),(j)和(k)是双层CuNPs-Oil/PVA水凝胶的断面图,可以看出上下层水凝胶的形貌是不同的,且上下两层紧密结合。经放大后比较,上层Oil/PVA/PEG水凝胶(图1(k))与下层CuNPs/PVA水凝胶相比(图1(j)),具有更多更大的孔隙,增加了CuNPs-Oil/PVA/PEG水凝胶作为伤口敷料的透气性。
(2)红外分析
FT-IR结果如图2.所示。对于纯的PVA水凝胶来说,在3700-3000cm-1之间出现了强而宽的吸收峰,这也出现在所有复合水凝胶中,归因于-OH的对称伸缩振动峰,PVA多聚物分子间的缔合,缔合体峰形较宽;2946.745cm-1,2910.586cm-1和1436.247cm-1为C-H的非对称伸缩振动和弯曲振动,1342.717cm-1处为C-H的对称弯曲,1087cm-1对应C-O键的伸缩。在942cm-1和948cm-1处可以观察到PVA、PEG的C-OH基团的吸收峰。CuNPs的加入没有改变PVA的峰形及峰强。在PVA/PEG中,PEG的-OH在3640cm-1处消失了,推测是在制备过程中已经被消耗完了。在1280.523cm-1和1242.435cm-1处发现,与没有添加PEG的水凝胶相比(如PVA、CuNPs/PVA),添加了PEG的水凝胶的吸收峰明显增强了(如PVA/PEG、Oil/PVA/PEG、共混CuNPs、Oil/PVA/PEG),这归因于PEG当中的-CH2。Oil/PVA/PEG水凝胶与共混的CuNPs、Oil的红外曲线相同,说明CuNPs的加入对原有物质不会产生影响。在1518.96cm-1处新增了烯烃RCH2=CH2的吸收峰,这是由于丁香油的加入。
(3)XRD分析
利用XRD测定了CuNPs的相纯度和晶体结构,显示出良好的结晶性和稳定性,只有与CuNPs相关的衍射峰(图3中(a)图所示)。对应的标准卡片为PDF-#99-0034。CuNPs的衍射峰出现在2θ为43.32°(111),50.45°(200),74.12°(220)。图3中(b)图和(c)图显示合成的CuNPs为片状,其平均厚度为185.45nm。
(4)机械性能及溶胀性能
为了验证不同材料复合水凝胶的机械性能,进行了拉伸试验。测试结果如图4.及表1.所示,随着CuNPs和Oil的加入,与纯PVA和PVA/PEG相比,CuNPs/PVA、Oil/PVA/PEG及CuNPs-Oil/PVA/PEG双层水凝胶的力学性能均得到了显著提升。CuNPs/PVA水凝胶的弹性模量、断裂应力、拉伸强度、最大力分别是PVA的2.6、2.3、2.6、2.1倍,断裂伸长率有所下降。PVA/PEG的弹性模量、断裂伸长率、断裂应力、拉伸强度在Oil加入后稍微有所降低,但其最大力有所提高,丁香精油与PVA/PEG之间的分子氢键增强了整体机械性能。对于双层CuNPs-Oil/PVA/PEG水凝胶,相比单层CuNPs/PVA、Oil/PVA/PEG水凝胶,其弹性模量、断裂应力和拉伸强度稍有下降。而断裂伸长率介于之间,最大力则得到了明显的增长,这是上、下两层水凝胶协同作用的结果,因此双层水凝胶的力学性能介于单层CuNPs/PVA和Oil/PVA/PEG水凝胶之间。为了检测双层水凝胶是否结合紧密,将水凝胶进行纵向的拉伸,结果发现其最大力增长了,其他力学参数相对横向测试时降低了。但足以证明,双层水凝胶结合紧密。
水凝胶的溶胀性能与力学性能是有一定关系的。如图所示4中的(a)图,各种水凝胶的溶胀性能是十分优异的。其中PVA的吸水能力最强,PVA的溶胀率在20h后达到其自身质量的1300%,CuNPs加入后PVA的溶胀性能稍微减弱,可能是因为CuNPs填补了PVA水凝胶的三维孔隙。对PVA/PEG来说,柔性PEG链与PV A链相互渗透,PEG作为造孔剂,如SEM图所示,PVA/PEG显示大量的孔隙,但其溶胀率低于PVA水凝胶的。疏水性的丁香油加入后Oil/PVA/PEG的溶胀性进一步降低,由于疏水性丁香油的加入。而由于下层CuNPs/PVA的优异溶胀性,双层CuNPs-Oil/PVA/PEG水凝胶的溶胀性有所上升。
综上所述,CuNPs-Oil/PVA/PEG双层水凝胶,上层具有杰出的力学性能,相对较弱的溶胀性及疏水性,下层具有优异的溶胀性及亲水性。
表1.机械性能测试结果
(5)抑菌性测试
本实验中,涉及到的抑菌实验具体方法如下:
1)抑菌实验开始前准备工作
实验台清洁干净后,用紫外灯杀菌消毒1h。
固体培养基的配置(500mL):5.0g蛋白胨、2.5g氯化钠、1.5g牛肉膏、6g琼脂,加热溶解于500mL去离子水中,调节pH在7.5左右。
将固体培养基以及实验所用玻璃仪器等置入高压灭菌蒸汽锅中处理20分钟左右。
菌种的活化:适量固体培养基倒入已灭菌试管并放置斜面使其冷却,取冷藏的细菌菌种,用灭菌的接种环刮取斜面菌种呈W字涂至新的试管斜面,并在恒温培养箱中(37℃,24h)活化细菌。待长出一层细菌后将斜面用0.9%的生理盐水刚好没过斜面,刮下斜面菌种溶于生理盐水中,最后将此液体倒入灭菌的锥形试管中,得到菌悬液。
2)抑菌圈法抑菌实验过程
配置固体培养基,同50mL离心管、若干培养皿、若干3mL和1mL移液枪枪头一起置于高压蒸汽灭菌锅中灭菌20分钟。待灭菌完毕,趁热将培养基分别倒入无菌培养皿中,使其静置冷却凝固。
用移液枪移取0.25mL菌悬液放入离心管中,添加10mL无菌水,此即为108菌悬液浓度,并做标记108。将108离心管充分震荡,使菌液混合均匀。另取一支1mL枪头,取108中菌悬液0.25mL置于新的离心管中,添加10mL无菌水稀释10倍,此即为107菌悬液,标记为107。重复上述过程直至得到106菌悬液。
取若干支1mL无菌移液枪头,分别吸取106的菌悬液0.1mL加入到若干固体培养基中,并用涂布器进行均匀涂布。最后将培养皿置于生化培养箱中(37℃)培养数小时,直至固体培养基上的菌液干燥。
将水凝胶切成直径为9mm的圆盘,放置在涂有大肠杆菌悬浮液的固体平板培养基上。膜在37℃恒温生化培养箱中培养。24h后测定抑菌区大小,计算抑菌活性比,计算公式如下:
其中A是测量的抑菌圈大小,A0是最大抑菌圈大小。
3)抑菌测试结果
①添加量对抑菌性的分析
从图5.中可以看出CuNPs(a)-(d)、丁香油(e)-(l)不同添加量对抑菌性的影响。整体来看,纯CuNPs水凝胶具有很小的抑菌性,水凝胶中的CuNPs随着时间逐渐被氧化为二价的Cu2+,表现为蓝色的水凝胶。然而,丁香油具有很强的抑菌性,添加0.5mL的丁香油时,由于水凝胶中的水份挥发而缩小。当逐渐增加丁香油的添加量时,抑菌性得到加强。当加入1mL油时,抑菌圈最大,同时发现,在制备和使用过程中,丁香油会从上层逐渐渗透至下层中,因此丁香油的存在,抑制了Cu2+子被氧化的程度,进而提升了下层水凝胶的抗氧化性。而后再增加油的量,抑菌性不变。考虑成本,选择1mL油作为最佳添加量。
②水凝胶的抑菌试验分析及抗菌耐久性试验
本实验采用抑菌圈法对双层水凝胶在制备各阶段的产物的抗菌性能(图6(a)-(f)),及抑菌持久性(图6(g)-(l))进行测试,结果如图6所示。研究发现,PVA、PVA/PEG水凝胶对大肠杆菌的抑制作用几乎为零。Oil/PVA/PEG、CuNPs/PVA水凝胶作为单层水凝胶,对大肠杆菌分别有较强、较弱的抑菌性,如图6.(c),(d)所示。与单层水凝胶相比,双层CuNPs-Oil/PVA/PEG水凝胶的上(Oil/PVA/PEG)、下(CuNPs/PVA)层对大肠杆菌的抑菌性均得到加强,尤其是下层CuNPs/PVA的抑菌性是原单层CuNPs/PVA水凝胶的2倍以上。这归因于上层Oil/PVA/PEG水凝胶中抑菌剂丁香油的向下渗透,而增强了下层的抑菌性。
伤口敷料在治愈过程中的抗菌耐久性是检验敷料使用性能的重要标准。图6(g)-(l)为CuNPs-Oil/PVA/PEG双层水凝胶应用耐久性试验结果(抗菌测试是连续的)。从图6(i)和(l)中可以看出,水凝胶上、下层在使用超过72小时后仍能保持良好的抗菌效果(使用双层水凝胶分别对其上、下层进行抑菌测试)。本实施例中所做的抗菌测试是连续的。由于抑菌剂在抑制细菌生长的过程中被消耗,抑制范围减小。与12h的抑菌圈(图6(g)和(j))相比,水凝胶的抑菌圈持续工作72h,尺寸略有减小,但抗菌性能仍达到最佳性能的83%左右。
实施例2
步骤一,片状CuNPs的合成:首先,在25mL去离子水中加入0.4g硫酸铜和0.1g十六烷基三甲基溴化铵,超声溶解,加热到86℃,滴加50μL氨水生成铜氨络合物,将配置好的1.2g/25mL抗坏血酸、0.4g/25mL环糊精溶液快速加入,抗坏血酸可将Cu2+还原为CuNPs,环糊精能够保护CuNPs不被迅速氧化。溶液颜色由蓝色变为暗黄色,最终生成红棕色沉淀,搅拌5分钟。离心得到片状铜纳米粒子。
步骤2,CuNPs-Oil/PVA/PEG双层抑菌水凝胶的制备:将合成的铜纳米粒子溶液2.5mL加入到溶解的聚乙烯醇(PVA)中,搅拌均匀。倒入六孔培养皿中冷冻结冰,即为下层。2g PVA加入15mL水中,86℃下搅拌溶解15min,加入0.3g聚乙二醇(PEG),缓慢滴加1mL丁香油溶解。将得到的溶胶倒在冻好的下层铜纳米粒子水凝胶上,即为上层。将其冻融循环4次,得到双层水凝胶。
实施例3
步骤一,片状CuNPs的合成:首先,在25mL去离子水中加入0.4g硫酸铜和0.4g十六烷基三甲基溴化铵,超声溶解,加热到87℃,滴加100μL氨水生成铜氨络合物,将配置好的1.3g/25mL抗坏血酸、0.1g/25mL环糊精溶液快速加入,抗坏血酸可将Cu2+还原为CuNPs,环糊精能够保护CuNPs不被迅速氧化。溶液颜色由蓝色变为暗黄色,最终生成红棕色沉淀,搅拌5分钟。离心得到片状铜纳米粒子。
步骤2,CuNPs-Oil/PVA/PEG双层抑菌水凝胶的制备:将合成的铜纳米粒子溶液2.5mL加入到溶解的聚乙烯醇(PVA)中,搅拌均匀。倒入六孔培养皿中冷冻结冰,即为下层。2g PVA加入15mL水中,87℃下搅拌溶解15min,加入0.42g聚乙二醇(PEG),缓慢滴加1mL丁香油溶解。将得到的溶胶倒在冻好的下层铜纳米粒子水凝胶上,即为上层。将其冻融循环5次,得到双层水凝胶。
实施例4
步骤一,片状CuNPs的合成:首先,在25mL去离子水中加入0.4g硫酸铜和0.3g十六烷基三甲基溴化铵,超声溶解,加热到88℃,滴加150μL氨水生成铜氨络合物,将配置好的1.4g/25mL抗坏血酸、0.2g/25mL环糊精溶液快速加入,抗坏血酸可将Cu2+还原为CuNPs,环糊精能够保护CuNPs不被迅速氧化。溶液颜色由蓝色变为暗黄色,最终生成红棕色沉淀,搅拌5分钟。离心得到片状铜纳米粒子。
步骤2,CuNPs-Oil/PVA/PEG双层抑菌水凝胶的制备:将合成的铜纳米粒子溶液2.5mL加入到溶解的聚乙烯醇(PVA)中,搅拌均匀。倒入六孔培养皿中冷冻结冰,即为下层。2g PVA加入15mL水中,88℃下搅拌溶解15min,加入0.45g聚乙二醇(PEG),缓慢滴加1mL丁香油溶解。将得到的溶胶倒在冻好的下层铜纳米粒子水凝胶上,即为上层。将其冻融循环3次,得到双层水凝胶。
实施例5
步骤一,片状CuNPs的合成:首先,在25mL去离子水中加入0.4g硫酸铜和0.45g十六烷基三甲基溴化铵,超声溶解,加热到89℃,滴加200μL氨水生成铜氨络合物,将配置好的1.5g/25mL抗坏血酸、0.3g/25mL环糊精溶液快速加入,抗坏血酸可将Cu2+还原为CuNPs,环糊精能够保护CuNPs不被迅速氧化。溶液颜色由蓝色变为暗黄色,最终生成红棕色沉淀,搅拌5分钟。离心得到片状铜纳米粒子。
步骤2,CuNPs-Oil/PVA/PEG双层抑菌水凝胶的制备:将合成的铜纳米粒子溶液2.5mL加入到溶解的聚乙烯醇(PVA)中,搅拌均匀。倒入六孔培养皿中冷冻结冰,即为下层。2g PVA加入15mL水中,89℃下搅拌溶解15min,加入0.7g聚乙二醇(PEG),缓慢滴加1mL丁香油溶解。将得到的溶胶倒在冻好的下层铜纳米粒子水凝胶上,即为上层。将其冻融循环4次,得到双层水凝胶。
实施例6
步骤一,片状CuNPs的合成:首先,在25mL去离子水中加入0.4g硫酸铜和0.3g十六烷基三甲基溴化铵,超声溶解,加热到90℃,滴加250μL氨水生成铜氨络合物,将配置好的0.8g/25mL抗坏血酸、0.4g/25mL环糊精溶液快速加入,抗坏血酸可将Cu2+还原为CuNPs,环糊精能够保护CuNPs不被迅速氧化。溶液颜色由蓝色变为暗黄色,最终生成红棕色沉淀,搅拌5分钟。离心得到片状铜纳米粒子。
步骤2,CuNPs-Oil/PVA/PEG双层抑菌水凝胶的制备:将合成的铜纳米粒子溶液2.5mL加入到溶解的聚乙烯醇(PVA)中,搅拌均匀。倒入六孔培养皿中冷冻结冰,即为下层。2g PVA加入15mL水中,98℃下搅拌溶解15min,加入0.4g聚乙二醇(PEG),缓慢滴加1mL丁香油溶解。将得到的溶胶倒在冻好的下层铜纳米粒子水凝胶上,即为上层。将其冻融循环5次,得到双层水凝胶。
实施例7
步骤一,片状CuNPs的合成:首先,在25mL去离子水中加入0.4g硫酸铜和0.5g十六烷基四甲基溴化铵,超声溶解,加热到85℃,滴加300μL氨水生成铜氨络合物,将配置好的1g/25mL抗坏血酸、0.35g/25mL环糊精溶液快速加入,抗坏血酸可将Cu2+还原为CuNPs,环糊精能够保护CuNPs不被迅速氧化。溶液颜色由蓝色变为暗黄色,最终生成红棕色沉淀,搅拌5分钟。离心得到片状铜纳米粒子。
步骤2,CuNPs-Oil/PVA/PEG双层抑菌水凝胶的制备:将合成的铜纳米粒子溶液2.5mL加入到溶解的聚乙烯醇(PVA)中,搅拌均匀。倒入六孔培养皿中冷冻结冰,即为下层。2g PVA加入15mL水中,85℃下搅拌溶解15min,加入0.49g聚乙二醇(PEG),缓慢滴加1mL丁香油溶解。将得到的溶胶倒在冻好的下层铜纳米粒子水凝胶上,即为上层。将其冻融循环4次,得到双层水凝胶。
以上所述仅为本发明的较佳实施例而已,并不用以限制本发明,凡在本发明的精神和原则之内,所作的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。
Claims (10)
1.一种铜纳米粒子-丁香油双层抑菌水凝胶的制备方法,其特征在于,包括以下步骤:
步骤1,在水中混合硫酸铜和十六烷基四甲基溴化铵,超声溶解后,加热,滴加氨水生成铜氨络合物;将抗坏血酸溶液和环糊精溶液加入至铜氨络合物中,制备得到片状铜纳米粒子;
步骤2,将片状铜纳米粒子加入到聚乙烯醇溶液中,均匀搅拌后的冷冻结冰得到双层抑菌水凝胶的下层;
步骤3,重新制备聚乙烯醇溶液,将重新制备的聚乙烯醇溶液和聚乙二醇混合,然后加入丁香油,得到溶胶;将得到的溶胶倒在双层抑菌水凝胶的下层上,形成过程产物,将过程产物冻融后,得到双层水凝胶。
2.根据权利要求1所述的一种铜纳米粒子-丁香油双层抑菌水凝胶的制备方法,其特征在于,步骤1中,硫酸铜和十六烷基四甲基溴化铵的混合质量比为:0.4:(0.1~0.5)。
3.根据权利要求1所述的一种铜纳米粒子-丁香油双层抑菌水凝胶的制备方法,其特征在于,步骤1中,加热温度为85~90℃。
4.根据权利要求1所述的一种铜纳米粒子-丁香油双层抑菌水凝胶的制备方法,其特征在于,步骤1中,滴加的氨水和硫酸铜的比例为(50-300)μL:0.4g。
5.根据权利要求1所述的一种铜纳米粒子-丁香油双层抑菌水凝胶的制备方法,其特征在于,步骤1中,抗坏血酸溶液的浓度为(0.8~1.5)g/25mL,环糊精溶液的浓度为(0.1~0.4)g/25mL。
6.根据权利要求1所述的一种铜纳米粒子-丁香油双层抑菌水凝胶的制备方法,其特征在于,步骤2中,片状铜纳米粒子和聚乙烯醇溶液的混合比例为0.155g:15mL。
7.根据权利要求1所述的一种铜纳米粒子-丁香油双层抑菌水凝胶的制备方法,其特征在于,步骤3中,重新制备的聚乙烯醇溶液浓度为2g/15mL,聚乙烯醇和聚乙二醇的混合质量比为2:(0.2-1)。
8.根据权利要求1所述的一种铜纳米粒子-丁香油双层抑菌水凝胶的制备方法,其特征在于,步骤3中,重新制备的聚乙烯醇溶液在85-90℃下搅拌均匀。
9.根据权利要求1所述的一种铜纳米粒子-丁香油双层抑菌水凝胶的制备方法,其特征在于,步骤3中,加入的丁香油和聚乙烯醇溶液的体积比为1:15。
10.一种通过权利要求1-9任意一项所述制备方法制得的铜纳米粒子-丁香油双层抑菌水凝胶,其特征在于,所述双层抑菌水凝胶中,下层为掺杂有片状铜纳米粒子的聚乙烯醇水凝胶,上层为包含丁香精油的聚乙烯醇/聚乙二醇水凝胶。
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