CN113413485A - 一种抗菌聚丙烯补片及其制备方法和应用 - Google Patents

一种抗菌聚丙烯补片及其制备方法和应用 Download PDF

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CN113413485A
CN113413485A CN202110827892.2A CN202110827892A CN113413485A CN 113413485 A CN113413485 A CN 113413485A CN 202110827892 A CN202110827892 A CN 202110827892A CN 113413485 A CN113413485 A CN 113413485A
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胡俊丽
刘益春
张慧
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Northeastern University China
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Abstract

本发明提供一种抗菌聚丙烯补片及其制备方法和应用，属于医用高分子材料领域。该补片包括聚丙烯网和设置在聚丙烯网上的抗菌性薄膜；所述的抗菌性薄膜是将壳聚糖醋酸盐、水溶性柔性高分子和抗菌肽通过静电纺丝得到的。本发明还提供一种抗菌聚丙烯补片的制备方法，本发明的补片具有优异的抗菌性能，且无毒作用，用于具有感染风险的疝修补手术，具有很好的前景。

Description

一种抗菌聚丙烯补片及其制备方法和应用
技术领域
本发明属于医用高分子材料领域，具体地涉及一种抗菌聚丙烯补片及其制 备方法。
背景技术
腹壁疝是我国的常见病和多发病，发病率为3‰～5‰，它无法自愈，必须通 过疝修补手术治疗，即使用补片对腹壁的薄弱部位进行修补和增强(唐健雄，《我 国疝外科的进展和存在的问题》，国际外科学杂志，2010年37卷第1期，3–5)。 然而，病人抵抗力差、手术复杂时间长、出血多、术前存在疝坎顿造成的肠管 坏死或局部污染等情况均可能引起补片感染并发症，发病率可高达1％～8％ (Falagas,M.E.and Kasiakou,S.K.,Mesh-relatedinfections after hernia repair surgery,Clin Microbiol Infect 2005,11,3–8)。补片感染一旦发生，处理非常困难， 导致住院时间延长、患者痛苦增加、费用升高，甚至需要二次手术或造成不可 逆转的恶性后果。因此，补片感染的防治是腹壁疝治疗亟需解决的关键问题。
使用具有抗菌功能的疝修补补片是预防补片感染的有效手段(Guillaume，O.， etal.Infections associated with mesh repairs of abdominal wall hernias：Areantimicrobial biomaterials the longed-for solution Biomaterials，167，2018，15–31)。 抗菌补片的开发自上世纪末以来就引起了国际上各大补片生产商的关注。例如， 美国戈尔公司(GORE)在1999年推出了负载碳酸银和醋酸氯己定的膨化聚四 氟乙烯抗菌合成补片(
Figure RE-GDA0003207845990000011
PLUS) (https：//www.goremedical.com/products/dualmeshplus)，美国巴德公司(BARD) 在2014年推出了含有利福平和米诺环素的脱细胞猪皮抗菌生物补片 (XenmatrixTMAB Surgical Graft)(https：//www.crbard.com/davol/en-us/products /xenmatrix-ab-surgical-graft)。然而，由于使用的抗菌试剂存在毒性高(碳酸银和 醋酸氯己定)和可能引起耐药性(利福平和米诺环素)的问题，这些抗菌补片 在临床上并未得到广泛应用。因此，亟需发展安全性和有效性更好的抗菌补片。
发明内容
本发明的目的是提供一种抗菌聚丙烯补片及其制备方法和应用，该补片具 有优异的抗菌性能，且无毒作用。
本发明首先提供一种抗菌聚丙烯补片，包括聚丙烯网和设置在聚丙烯网上 的抗菌性薄膜；所述的抗菌性薄膜是将壳聚糖醋酸盐、水溶性柔性高分子和抗 菌肽通过静电纺丝得到的。
优选的是，所述的水溶性高分子为聚氧化乙烯、聚乙烯醇或聚乙烯吡咯烷 酮。
优选的是，所述的抗菌肽包括粘菌素、多粘菌素、万古霉素、短杆菌素D、 杆菌素、达托霉素、特拉万星、奥利万星或达巴万星中的一种或几种。
本发明还提供一种抗菌聚丙烯补片的制备方法，包括：
步骤一：将壳聚糖乙酸盐、水溶性柔性高分子和抗菌肽混合，然后通过静 电纺丝，得到纳米纤维膜；
步骤二：将壳聚糖乙酸盐溶液涂抹在聚丙烯网的表面，再平铺步骤一得到 的纳米纤维膜，风干后得到抗菌聚丙烯补片。
优选的是，所述的步骤一中抗菌肽的质量百分含量为5％～30％，水溶性柔 性高分子的质量百分含量为5％～30％。
优选的是，所述的静电纺丝的条件为：6～30kV电压，10～30cm喷丝头与接 收器距离。
优选的是，所述的步骤二中壳聚糖乙酸盐溶液的浓度为0.5％～5％。
本发明还提供上述抗菌聚丙烯补片作为修补材料在治疗腹壁疝中的应用。
本发明的有益效果
本发明首先提供一种抗菌聚丙烯补片，具有优异的抗菌性能，且无毒作用， 该抗菌性薄膜同时具有优异的耐水性能，能在腹壁存留较长时间，从而防止手 术后肠管等腹腔内器官与补片之间的粘连，避免疼痛等并发症的发生。因此本 发明提供的抗菌聚丙烯补片用于具有感染风险的疝修补手术，具有很好的前景。
本发明的制备方法简易，易于规模化生产。
附图说明
图1为本发明实施例1中空白的(a)和复合含20％粘菌素的壳聚糖纳米纤 维膜(b)的聚丙烯补片对大肠杆菌的抑制效果；
图2为本发明实施例2中复合含5％粘菌素和5％万古霉素的壳聚糖纳米纤 维膜的聚丙烯补片对大肠杆菌(a)和金黄色葡萄球菌(b)的抑制效果；
图3为本发明实施例2中L929小鼠成纤维细胞在复合含5％粘菌素和5％万 古霉素的壳聚糖纳米纤维膜的聚丙烯补片的浸出液中的存活率；
图4为本发明实施例3中复合含2.5％粘菌素和2.5％万古霉素的壳聚糖纳米 纤维膜的聚丙烯补片对大肠杆菌(a)和金黄色葡萄球菌(b)的抑制效果。
具体实施方式
本发明首先提供一种抗菌聚丙烯补片，包括聚丙烯网和设置在聚丙烯网上 的抗菌性薄膜；所述的抗菌性薄膜是将壳聚糖醋酸盐、水溶性柔性高分子和抗 菌肽通过静电纺丝得到的。所述的聚丙烯网为医用聚丙烯网，来源为商购。
按照本发明，所述的水溶性高分子优选为聚氧化乙烯、聚乙烯醇或聚乙烯 吡咯烷酮，更优选为聚氧化乙烯。
按照本发明，所述的抗菌肽优选包括粘菌素、多粘菌素、万古霉素、短杆 菌素D、杆菌素、达托霉素、特拉万星、奥利万星或达巴万星中的一种或几种。
本发明还提供一种抗菌聚丙烯补片的制备方法，包括：
步骤一：将壳聚糖乙酸盐、水溶性柔性高分子和抗菌肽混合，然后通过静 电纺丝，得到纳米纤维膜；所述的壳聚糖乙酸盐是将壳聚糖溶解到乙酸水溶液 中，搅拌溶解，然后用水透析，冻干，或者用醇类溶剂沉降、洗涤，再真空干 燥；所述的乙酸水溶液的浓度优选为0.1～10％，更优选为0.5～2％；所述的抗菌 肽的质量百分含量优选为5％～30％，水溶性柔性高分子的质量百分含量优选为 5％～30％；所述的静电纺丝的条件优选为：6～30kV电压，10～30cm喷丝头与接 收器距离。
步骤二：将壳聚糖乙酸盐溶液涂抹在聚丙烯网的表面，再平铺步骤一得到 的纳米纤维膜，使聚丙烯补片和纳米纤维膜粘贴良好，风干后得到抗菌聚丙烯 补片。所述的壳聚糖乙酸盐溶液的浓度优选为0.5％～5％，壳聚糖乙酸盐溶液的 涂抹量优选为10μL/cm2。
本发明还提供上述抗菌聚丙烯补片作为修补材料在治疗腹壁疝中的应用。
下面采用具体的实施例进一步说明本发明，但本发明并不限于此。
实施例1：复合含20％粘菌素的壳聚糖纳米纤维膜的聚丙烯补片
(1)配制壳聚糖醋酸盐、粘菌素和聚氧化乙烯(分子量500万)的混合溶 液，其中壳聚糖醋酸盐与聚氧化乙烯的质量比为80：20，粘菌素占溶质总质量 的20％。向混合溶液施加24kV的高压，静电纺丝，在25cm处接收纳米纤维 膜。
(2)配制1％的壳聚糖醋酸盐的水溶液，按照10μL/cm2的用量将其涂抹在 医用聚丙烯网片的光滑面，再在其上平铺第一步所得纳米纤维膜，使聚丙烯补 片和纳米纤维膜粘贴良好，自然风干。
以大肠杆菌作为代表性的革兰氏阴性菌，测试样品的抗菌性能。切取直径 为8mm的圆片形样品，放置于涂有大肠杆菌的琼脂糖培养板，37度恒温培养 24小时，观察抑菌圈的大小，评价样品对大肠杆菌的抗菌性能。如图1所示， 原空白聚丙烯补片(a)周围无抑菌圈产生，表明其不具有抗菌性，而复合含20％ 粘菌素的壳聚糖纳米纤维膜的聚丙烯补片(b)周围产生明显的抑菌圈，表明其 对大肠杆菌具有优异的抗菌性能。
实施例2：复合含5％粘菌素和5％万古霉素的壳聚糖纳米纤维膜的聚丙烯补 片。
(1)配制壳聚糖醋酸盐、粘菌素、万古霉素和聚氧化乙烯(分子量500万) 的混合溶液，其中壳聚糖醋酸盐与聚氧化乙烯的质量比为80：20，粘菌素和万 古霉素分别占溶质总质量的5％。向混合溶液施加20kV的高压，静电纺丝，在 25cm处接收纳米纤维膜。
(2)配制1％的壳聚糖醋酸盐的水溶液，按照10μL/cm2的用量将其涂抹在 医用聚丙烯网片的光滑面，再在其上平铺第一步所得纳米纤维膜，使聚丙烯补 片和纳米纤维膜粘贴良好，自然风干。
以大肠杆菌作为代表性的革兰氏阴性菌，以金黄色葡萄球菌为代表性的革 兰氏阳性菌，测试样品的抗菌性能。切取直径为8mm的圆片形样品，分别放置 于涂有大肠杆菌和金黄色葡萄球菌的琼脂糖培养板，分别测试样品对大肠杆菌 和金黄色葡萄球菌的抗菌性能。如图2所示，在两种细菌的培养板上，样品周 围都产生明显的抑菌圈，表明其对革兰氏阴性菌和阳性菌都具有优异的抗菌性 能，样品具有广谱抗菌性。
以L929小鼠成纤维细胞为例，测试实施例2样品的生物相容性。将10mg 样品浸泡于2mLDMEM培养基中，37度恒温培养24小时，之后去除样品，得 到浸出液，使用DMEM稀释不同程度，得到不同浓度的浸出液。将不同浓度的 浸出液加入到种植好L929小鼠成纤维细胞的96孔细胞培养板孔中(5000个细 胞/孔)，以纯DMEM培养基作为对照，37度恒温培养24小时，用MTT法对孔 内细胞定量，测定细胞存活率。结果如图3所示，在0.031～5mg/mL的浸出液浓 度范围内，细胞存活率都在80％以上，表明样品具有良好的生物相容性。
实施例3：复合含2.5％粘菌素和2.5％万古霉素的壳聚糖纳米纤维膜的聚丙 烯补片。
(1)配制壳聚糖醋酸盐、粘菌素、万古霉素和聚氧化乙烯(分子量500万) 的混合溶液，其中壳聚糖醋酸盐与聚氧化乙烯的质量比为80：20，粘菌素和万 古霉素分别占溶质总质量的2.5％。向混合溶液施加20kV的高压，静电纺丝， 在25cm处接收纳米纤维膜。
(2)配制1％的壳聚糖醋酸盐的水溶液，按照10μL/cm2的用量将其涂抹在 医用聚丙烯网片的光滑面，再在其上平铺第一步所得纳米纤维膜，使聚丙烯补 片和纳米纤维膜粘贴良好，自然风干。
以实施例2所述方法测试样品对大肠杆菌和金黄色葡萄球菌的抗菌性能。如 图4所示，在两种细菌的培养板上，样品周围都产生明显的抑菌圈，表明其对 革兰氏阴性菌和阳性菌都具有优异的抗菌性能，样品具有广谱抗菌性。

Claims (8)

1.一种抗菌聚丙烯补片，包括聚丙烯网和设置在聚丙烯网上的抗菌性薄膜；其特征在于，所述的抗菌性薄膜是将壳聚糖醋酸盐、水溶性柔性高分子和抗菌肽通过静电纺丝得到的。
2.根据权利要求1所述的一种抗菌聚丙烯补片，其特征在于，所述的水溶性高分子为聚氧化乙烯、聚乙烯醇或聚乙烯吡咯烷酮。
3.根据权利要求1所述的一种抗菌聚丙烯补片，其特征在于，所述的抗菌肽包括粘菌素、多粘菌素、万古霉素、短杆菌素D、杆菌素、达托霉素、特拉万星、奥利万星或达巴万星中的一种或几种。
4.根据权利要求1所述的一种抗菌聚丙烯补片的制备方法，其特征在于，包括：
步骤一：将壳聚糖乙酸盐、水溶性柔性高分子和抗菌肽混合，然后通过静电纺丝，得到纳米纤维膜；
步骤二：将壳聚糖乙酸盐溶液涂抹在聚丙烯网的表面，再平铺步骤一得到的纳米纤维膜，风干后得到抗菌聚丙烯补片。
5.根据权利要求4所述的一种抗菌聚丙烯补片的制备方法，其特征在于，所述的步骤一中抗菌肽的质量百分含量为5％～30％，水溶性柔性高分子的质量百分含量为5％～30％。
6.根据权利要求4所述的一种抗菌聚丙烯补片的制备方法，其特征在于，所述的静电纺丝的条件为：6～30kV电压，10～30cm喷丝头与接收器距离。
7.根据权利要求4所述的一种抗菌聚丙烯补片的制备方法，其特征在于，所述的步骤二中壳聚糖乙酸盐溶液的浓度为0.5％～5％。
8.权利要求1所述的抗菌聚丙烯补片作为修补材料在治疗腹壁疝中的应用。
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