论文总字数：18252字

摘 要

医疗器械植入感染已经成为了制约现代医学发展的一大难题，其中最为常见的就是医用导管相关感染。现役医用导管多为聚氨酯（TPU）和硅胶等疏水性材料，抗菌性能差，在使用过程中极易引起细菌感染，造成医疗感染提高病人发病率和致死率，所以抗菌涂层的研发具有必要性和迫切性。聚赖氨酸（PL）是一种生物毒性低且热稳定性好的高分子广谱抗菌聚合物，但是由于PL极易溶于水的特性，它很难长期稳定的附着在医用导管等疏水性固体表面，以形成良好的抗菌涂层。所以本论文主要研究了基于PL的生物相容性好、涂层稳定、广谱抗菌的抗菌涂层的构建和表征，具体内容分为以下几部分：（1）把阳离子聚电解质聚赖氨酸（PL）通过静电相互作用和阴离子表面活性剂1,4-双（2-乙基己基）磺基琥珀酸钠（AOT）复合，制备出溶于乙醇但不溶于水的抗菌复合物PL-AOT，通过¹H NMR检测，验证PL-AOT的具体结构。¹H NMR谱图表明，PL-AOT复合成功。（2）通过浸泡法，使PL-AOT在TPU表面形成一层抗菌涂层，并通过接触角测试和XPS元素组成分析，验证涂层是否构建成功。涂层成功的TPU表面接触角从92.36°骤降至44.15°，且表面元素组成中N、S元素含量大大提高，表明涂层的成功构建。（3）用PL-AOT对聚氨酯导管（Cat）进行涂层，并对比涂层成功的聚氨酯导管（Cat/PL-AOT）和未涂层的Cat对革兰氏阴性菌大肠杆菌和革兰氏阳性菌金黄色葡萄球菌的抑菌能力差异，表征涂层的抗菌性能。铺板菌落计数结果显示，PL-AOT涂层能在短时间内杀死几乎100%的细菌，表明该复合物杀菌能力强、广谱抗菌活性高。

关键词：医用导管 抗菌涂层 聚赖氨酸 静电作用

Construction and characterization of the antibacterial and super-lubricated surface coating of a medical catheter

ABSTRACT

Implantable infection of medical devices has become a major problem that restricts the development of modern medicine, among which the most common one is catheter-related infection.Currently, most of the active medical catheters are hydrophobic materials such as polyurethane (TPU) and silicone, which have poor antibacterial performance. During the use, they are easy to cause bacterial infection, resulting in higher morbidity and mortality of patients. Therefore, the research and development of antibacterial coating is of necessity and urgency.Polylysine (PL) is a very safe antibacterial polymer with good biocompatibility, bactericidal ability and thermal stability. However, due to the fact that PL is easily soluble in water, it is difficult for PL to adhere to the hydrophobic solid surface such as medical catheter for a long time to form a good antibacterial coating. Therefore, this paper mainly studies the construction and characterization of the antibacterial coating based on PL，which has good biocompatibility, long-term stability and broad-spectrum antibacterial.，specific content can be divided into the following.(1) The antibacterial compound PL-AOT, soluble in ethanol but insoluble in water, was synthesized by electrostatic interaction between the cation polyelectrolyte polylysine (PL) and the anionic surfactant 1,4-bis（2-ethylhexyl）sulfosuccinate (AOT). The structure of PL-AOT was verified by ¹H NMR. ¹H NMR spectra showed that PL-AOT was successfully compounded. (2) Pl-AOT was used to form an antibacterial coating on the TPU surface by immersion method, and the coating was verified to be successfully constructed by Contact Angle test and XPS element composition analysis. The surface Contact Angle of TPU successfully adhered by the coating decreased sharply from 92.36° to 44.15°, and the content of N and S elements in the surface element composition increased greatly, indicating the successful construction of the coating.(3) The polyurethane catheter (Cat) was coated with PL-AOT. The antibacterial properties of the coated polyurethane catheter (Cat/PL-AOT) were compared with those of the uncoated Cat against gram-negative escherichia coli and gram-positive staphylococcus aureus.The results showed that PL-AOT coating could kill almost 100% bacteria in a short time, indicating that the complex had strong bactericidal capacity and high broad-spectrum antibacterial activity.

Key Words：Medical catheter;Antibacterial coating;Polylysine;Electrostatic interaction

目 录

摘 要 I

ABSTRACT II

第一章 前言 1

1.1 医用导管相关感染 1

1.1.1 医用导管相关感染现状 1

1.1.2 医用导管相关感染产生机理 2

1.1.3 医用导管抗菌表面的构建 2

1.2 聚赖氨酸（PL） 3

1.2.1 PL的结构 4

1.2.2 PL的生物学性质 4

1.2.3 PL的抗菌机理 4

1.3 本文思路 4

1.3.1 PL-AOT的合成 4

1.3.2 PL-AOT的表征 5

1.3.3 构建并表征PL-AOT抗菌涂层 5

1.3.4 PL-AOT抗菌涂层抗菌性能的表征 5

第二章 基于聚赖氨酸的抗菌表面的构建及表征 7

2.1 引言 7

2.2 药品与仪器 8

2.3 实验方法 9

2.3.1 PL-AOT 复合物的合成及表征 9

2.3.2 抗菌表面的构建 9

2.3.3 TPU表面亲疏水性能表征 10

2.3.4 XPS样品表面元素组成表征 10

2.3.5 聚氨酯医用导管内的涂层 10

2.3.6 Cat导管内侧抗菌涂层抗菌性实验 10

第三章 结果与讨论 11

3.1 PL-AOT抗菌复合物的表征 11

3.2 TPU表面亲疏水性能表征结果 11

3.3 XPS样品表面元素组成表征结果 12

3.4 Cat导管内侧抗菌涂层抗菌性实验结果 14

3.5 结论 15

第四章 结论与展望 16

4.1 结论 16

4.2 展望 16

参考文献 17

致谢 20

前言

1.1 医用导管相关感染

与医疗植入物相关的感染正变得越来越普遍，并导致显著的发病率，在某些情况下，还会导致死亡。自1987年以来，GRISTINA等研究人员一直强调植入类医疗器械的主要缺点仍然是“细菌可能会粘附于生物材料表面，导致以生物材料为中心的感染”^[1]。虽然政府和医院方面已经在防治医疗感染方面花费了大量精力，例如设置隔离室杜绝病人接触致病菌从而引起感染或者通过规范和提高医生护士的诊疗手段来降低诊疗期间植入体所受到的污染，但是由细菌引起的植入类医疗器械感染依然无法杜绝。细菌极易在植入物的表面定植并形成生物膜，在体内时由于局部免疫抑制的存在，这一过程还会被加速。万一发生植入体感染，唯一的办法就是手术取出植入体，这一过程不仅需要严苛的技术条件和高昂的治疗经费，还会对病患和医护人员产生极大的潜藏风险。所以，防患植入物相关感染最简单有效的方法是在植入物表面构建抗菌涂层。

请支付后下载全文，论文总字数：18252字