CN113956508A - 一种温敏型聚阳离子抗菌凝胶、制备方法及其应用 - Google Patents
一种温敏型聚阳离子抗菌凝胶、制备方法及其应用 Download PDFInfo
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Abstract
本发明涉及水凝胶制备技术领域，具体涉及一种温敏型聚阳离子抗菌凝胶、制备方法及其应用；将阳离子单体与温敏型单体共聚得到共聚物，随后与一定比例的水互溶，即可得到温敏型聚阳离子抗菌凝胶。本发明公开的温敏型聚阳离子抗菌凝胶在低温下呈流动的溶液态，温度升至25℃时，即可转为凝胶态；本发明公开的温敏型聚阳离子抗菌凝胶能够与带负电荷的细菌细胞膜结合，导致细菌细胞膜结构发生破坏，使细菌死亡，是一种高效安全的抗菌凝胶。
Description
技术领域
本发明涉及水凝胶制备技术领域，具体涉及一种温敏型聚阳离子抗菌凝胶、制备方法及其应用。
背景技术
近些年来，由于抗生素的广泛开发和应用，许多细菌产生耐药性，导致部分细菌感染难以治疗。为了有效杀伤细菌并避免产生耐药性，许多金属盐、金属纳米、阳离子抗菌剂被开发并应用于抗菌领域。由于部分用于抗菌的金属盐、金属纳米使用不当会对健康造成一定损害，所以在实际应用中存在一定限制。对于阳离子抗菌剂来说，由于细菌细胞膜呈电负性，携带正电荷的阳离子抗菌剂很容易与细菌细胞膜产生静电吸附作用，从而破坏细菌细胞膜的完整性，进而杀死细菌。此外，由于人体细胞由于人体环境的复杂性，一般不携带电荷，因此大部分阳离子抗菌剂具有较好的特异性识别细菌和较高的安全性的特点，非常适用于创面抗菌。
对于大部分抗菌剂来说，一般都呈液体形式，由于粘度较低，非常容易在创面流失，从而降低抗菌效果。因此抗菌凝胶作为一种长期稳定的抗菌制剂，非常适用于创面抗菌。但是部分凝胶的粘附力较强，在更换敷料时难以除尽，存在一定的安全隐患。此外，大部分抗菌凝胶在制备时直接呈凝胶状，流动性较差，因此对于深层的创口很难有较高的覆盖。
鉴于上述缺陷，本发明创作者经过长时间的研究和实践终于获得了本发明。
发明内容
本发明的目的在于解决现有的抗菌凝胶在制备时直接呈凝胶状，流动性较差，对深层创口很难有较高的覆盖的问题，提供了一种温敏型聚阳离子抗菌凝胶、制备方法及其应用。
为了实现上述目的，本发明公开了一种温敏型聚阳离子抗菌凝胶，包括聚阳离子链段和温敏型链段组成的共聚物和水，所述共聚物分子量为10000-200000。
所述聚阳离子链段由甲基丙烯酰氧乙基三甲基氯化铵、丙烯酰氧乙基三甲基氯化铵、丙烯酰氧乙基二甲基苄基氯化铵和二甲基二烯丙基氯化铵中的任意一种聚合所得，所述温敏型链段由N-异丙基丙烯酰胺聚合所得。
本发明还公开了上述温敏型聚阳离子抗菌凝胶的制备方法，包括以下步骤：
S1：制备温敏型阳离子共聚物：通过自由基聚合，将所述阳离子单体和N-异丙基丙烯酰胺共聚，即可得到温敏型阳离子共聚物；
S2：制备温敏型聚阳离子抗菌凝胶：将所述的温敏型阳离子共聚物与一定比例的水共溶，即可得到温敏型小聚阳离子抗菌凝胶。
所述步骤S1中阳离子单体与N-异丙基丙烯酰胺的摩尔比为5:1～1:10。
所述步骤S1中共聚方法为无规共聚和嵌段共聚。
所述步骤S2中温敏型阳离子共聚物与水的质量比为1:1～1:10。
本发明还公开了上述温敏型聚阳离子抗菌凝胶在创面抗菌中的应用。
与现有技术比较本发明的有益效果在于：
(1)本发明利用易获得的原料，制备过程主要在水中，极大的减少有机溶剂的使用，并且合成过程简单。
(2)本发明的温敏型聚阳离子抗菌凝胶，在低温下具有良好的水溶性，当与皮肤接触时，可以转变为凝胶态，可以更好的覆盖不规则的创口，并且避免抗菌剂的流失。
(3)本发明的温敏型聚阳离子抗菌凝胶，具有良好的抗菌性能，同时对正常组织具有良好的安全性，是一种高效、安全的抗菌凝胶。
附图说明
图1为实施例1制备的温敏型聚阳离子抗菌凝胶在不同温度的水中成胶照片；
图2为温敏型阳离子抗菌凝胶的最小抑菌浓度曲线；
图3为不同浓度温敏型阳离子抗菌凝胶与金葡萄菌共培养图；
图4为温敏型阳离子抗菌凝胶与市购的抗菌凝胶与金葡萄菌共培养图。
具体实施方式
以下结合附图，对本发明上述的和另外的技术特征和优点作更详细的说明。
实施例1
一种温敏型聚阳离子抗菌凝胶的制备：
S1：制备温敏型阳离子共聚物：
(1)合成聚丙烯酰氧乙基三甲基氯化铵(P-DAC)：21mg S-硫代苯甲酰巯基乙酸、0.78g丙烯酰氧乙基三甲基氯化铵和6mg AIBN溶于10mL去离子水中，通过通氮除氧后，70℃聚合16h。反应结束后在乙醇中沉降，干燥后即得0.7g P-DAC。
(2)合成P-DAC-b-NIPAM：将0.7g P-DAC、1.13g N-异丙基丙烯酰胺和9mg AIBN溶于20mL去离子水中，通过通氮除氧后，70℃聚合24h。反应结束后在乙醇中沉降，干燥后即得1.6g P-DAC-b-NIPAM。
S2：制备温敏型聚阳离子抗菌凝胶：
将S1所得的P-DAC-b-NIPAM(1g)溶于3mL去离子水，即得温敏型聚阳离子抗菌凝胶。
将上述所得的温敏型聚阳离子抗菌凝胶，装入注射器中，随后，分别向16℃、30℃的水中挤入0.2mL温敏型聚阳离子抗菌凝胶，如图1所示，在16℃的水中无法成胶并且具有良好的水溶性，在30℃的水中成胶效果明显，证明所制备的温敏型聚阳离子抗菌凝胶具有良好的热成胶性能。
实施例2
一种温敏型聚阳离子抗菌凝胶的制备：
S1：制备温敏型阳离子共聚物：
1.5g丙烯酰氧乙基三甲基氯化铵、5g N-异丙基丙烯酰胺和20mg AIBN溶于50mL去离子水中，除氧通氮后，70℃聚合物8h。反应结束在乙醇中沉降，干燥后即得5.2g温敏型阳离子共聚物P-DAC-co-NIPAM。
S2：制备温敏型聚阳离子抗菌凝胶：
将1g步骤S1所得P-DAC-co-NIPAM溶于4mL去离子水，即得温敏型聚阳离子抗菌凝胶。通过向30℃的水中注射，证明了该抗菌凝胶具有温敏性。
实施例3
将实施例1所制备的温敏型阳离子共聚物P-DAC-b-NIPAM进行抗菌实验：首先在液态培养基中将金黄色葡萄球菌培养至数量为108CFU/mL(通过紫外-可见吸收光谱仪测试600nm吸收值所计算而得)，稀释至1000倍至105CFU/mL。随后取0.1mL菌液分别与5mg/mL、10mg/mL、20mg/mL、40mg/mL、80mg/mL的P-DAC-b-NIPAM水溶液1mL在37℃恒温箱中共培养24h，每4h取样测试600nm处吸收值，对照组为等体积的水与相同量的菌液混合。如图2所示，在浓度为10mg/mL时，细菌的增殖被有效抑制，因此其最小抑菌浓度为10mg/mL。
取0.1mL浓度为105CFU/mL的金葡菌液分别与0.1mL的浓度为5mg/mL、10mg/mL、20mg/mL、40mg/mL、80mg/mL的P-DAC-b-NIPAM水溶液共混，随后共培养2h。培养结束后进行涂板，在37℃恒温培养箱中共培养24h，观察菌落数。如图3所示，在浓度为20mg/mL时，培养板上几乎无菌群可以被观察到，因此其最小杀菌浓度为20mg/mL。
实施例4
将实施例1所制备的温敏型阳离子抗菌凝胶进行抗菌测试：取0.1mL浓度为105CFU/mL的金葡菌液进行涂板，随后滴入所制备的抗菌凝胶，对照组采用市购的抗菌凝胶，在37℃恒温培养箱中共培养24h。如图4所示，实施例1所制备的温敏型阳离子抗菌凝胶的抑菌圈明显大于市购的抗菌凝胶，证明本发明所制备的温敏型抗菌凝胶具有良好的抗菌性能。
以上所述仅为本发明的较佳实施例，对本发明而言仅仅是说明性的，而非限制性的。本专业技术人员理解，在本发明权利要求所限定的精神和范围内可对其进行许多改变，修改，甚至等效，但都将落入本发明的保护范围内。
Claims (7)
1.一种温敏型聚阳离子抗菌凝胶，其特征在于，包括聚阳离子链段和温敏型链段组成的共聚物和水，所述共聚物分子量为10000-200000。
2.如权利要求1所述的一种温敏型聚阳离子抗菌凝胶，其特征在于，所述聚阳离子链段由甲基丙烯酰氧乙基三甲基氯化铵、丙烯酰氧乙基三甲基氯化铵、丙烯酰氧乙基二甲基苄基氯化铵和二甲基二烯丙基氯化铵中的任意一种聚合所得，所述温敏型链段由N-异丙基丙烯酰胺聚合所得。
3.一种如权利要求1或2所述的温敏型聚阳离子抗菌凝胶的制备方法，其特征在于，包括以下步骤：
S1：制备温敏型阳离子共聚物：通过自由基聚合，将所述阳离子单体和N-异丙基丙烯酰胺共聚，即可得到温敏型阳离子共聚物；
S2：制备温敏型聚阳离子抗菌凝胶：将所述的温敏型阳离子共聚物与一定比例的水共溶，即可得到温敏型小聚阳离子抗菌凝胶。
4.如权利要求3所述的一种温敏型聚阳离子抗菌凝胶的制备方法，其特征在于，所述步骤S1中阳离子单体与N-异丙基丙烯酰胺的摩尔比为5:1～1:10。
5.如权利要求3所述的一种温敏型聚阳离子抗菌凝胶的制备方法，其特征在于，所述步骤S1中共聚方法为无规共聚和嵌段共聚。
6.如权利要求3所述的一种温敏型聚阳离子抗菌凝胶的制备方法，其特征在于，所述步骤S2中温敏型阳离子共聚物与水的质量比为1:1～1:10。
7.一种如权利要求1或2所述的温敏型聚阳离子抗菌凝胶在创面抗菌中的应用。
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