高声阻抗聚合物介入导管材料制备及其超声成像性能研究

Interventional catheterization is a widely used clinical treatment, which enables timely and accurate assessment of patient situation and early diagnosis. However, catheter is easy to migrate away from the right path and position during insertion procedure, which may cause serious infection or complications and result in fatal consequence. As the risk of catheter malposition is quite high, accurate guidance of catheter becomes imperative. X-ray and computed tomography (CT) are currently common used for confirming catheter position. Nonetheless, these methods bring a risk to the patient of radiation exposure. Besides, expensive equipment and complicated procedure are required to conduct the guidance for catheter placement using X-ray or CT. Therefore, it is almost impossible to achieve bedside assessment by these methods. Ultrasound probe is a convenient, non-invasive, non-ray radiation technique and is safe to patient. These advantages exhibit great potential to real-time track moving catheter inside body and to accurately confirm catheter placement via ultrasonic guidance. Unfortunately, polymeric catheters currently used have similar acoustic impedance (AI) to that of human tissues, which results in poor visibility of catheter. This project aims to obtain composite catheter material with high AI by filling catheter polymer with inorganic powder possessing a large AI value. Intensive investigation will be completed to improve dispersion of highly polar inorganic fillers in a non-polar polyolefin matrix and enhance the interfacial interaction. Experiments will be carried out to reveal the effects of the composition, morphology, filling amount of the inorganic filler and its dispersion level in the polymer matrix, and the processing condition for the composite obtained et al on various properties of the material and catheter, including acoustic property, mechanical property, medical safety and ultrasonic visibility. The proposed research may provide key scientific basis for developing novel ultrasonic visible catheters, which is believed to significantly promote the establishment of high-accuracy ultrasound-guided catheter placement system.

介入置管是临床中常见诊疗手段，但置管失败或置管位置的偏移常常延误救治，导致严重并发症甚至死亡。因此确保快速、准确和安全的介入置管极为关键。目前介入置管的导入和位置确认主要依赖X射线透视和CT检查等方法，这些方法都有射线暴露，且所需检查条件高、操作实施复杂。超声探测具有便利、无创、无辐射的优势，是置管导入和定位的可能选择。目前常用聚合物导管材料的声阻抗与人体组织接近，置入体内的导管在超声图像中模糊不清，难以准确定位。本研究拟在导管聚合物中填充高声阻抗无机粉体，解决极性的无机粉体在非极性聚烯烃聚合物基体中的均匀分散难题，强化界面相互作用，获得高声阻抗复合导管材料，揭示填料组成、形态、添加量及其在聚合物基体中的分散状况、加工成型工艺等对导管声学性能、力学性能、医学安全性及超声显像性能的影响规律，为超声可视化新型介入导管的开发应用提供科学依据。课题的实施对建立精确超声引导介入置管术意义重大。

超声引导介入置管是临床诊疗尤其是急诊诊疗的新手段，但现有介入导管的超声成像效果较差，限制了超声引导介入置管的推广应用。为了解决上述问题，本课题通过在导管聚合物中填充高声阻抗无机粉体，开发了一种具有良好超声显影效果的医用介入导管材料。研究了无机粉体种类、添加量以及分散状况对于复合材料超声成像性能的影响。并考察了超声显影导管材料的力学性能、加工性能和生物安全性能。主要研究工作包括：.1.确定了高声阻抗介入导管材料的基本配方体系，并通过实验验证了本研究基本思路的可行性。.2.基于Image J图像分析软件，通过分析不同无机粉体-聚合物复合材料样品的超声图像灰度（光点亮度）曲线和辉度（光密度）比值，建立了一种导管材料超声成像性能的量化表征方法。.3.通过理论预测和实验探究了无机填料种类及添加量对复合材料声学性能的影响规律。结果显示：当无机填料的声阻抗高于聚合物基体声阻抗的5倍后，无机填料声阻抗的进一步增大对所得复合材料的声阻抗影响较小；随着复合材料中无机填料含量的增加，材料的复合声阻抗有所提高，材料的超声成像效果改善显著。.4.揭示了无机填料粒径对复合材料超声成像性能的影响规律。结果表明：增大无机填料在聚合物基体中的分散尺寸有助于提高材料的超声显影效果。结合声波散射特性，建议无机填料在聚合物中的分散尺寸应大于超声波长的1/10。.5.考察了超声显影导管材料的灭菌耐受性和浸提液特性，结果表明：所得Al2O3/聚烯烃导管材料能够经受水蒸汽灭菌的湿热条件（即121℃，30min）考验，灭菌前后材料的DSC曲线和力学性能未见明显变化。导管材料在不同浸提条件下得到的生理盐水浸提液的HPLC谱图与空白对照样无明显差别，未出现新峰，说明材料中的添加剂不会迁移出材料。同时，不溶性颗粒检测结果和溶血率亦符合相关规定的要求。.6.考察了复合材料导管在动物体内的超声影像，结果表明：Al2O3/聚烯烃导管在动物体内的超声影像清晰度优于现有商业介入导管。.