Non-coating anti-microbial, anti-host protein deposition, anti-inflammatory urinary catheter

摘要：导尿管相关性尿路感染(CAUTI)是尿路感染最常见的类型。 与医疗保健相关的感染，但目前还没有有效的技术来解决 问题就在这里。导管表面的抗微生物(抗生物膜)功能是一个重要的领域 这已经获得了很多关注；然而，由于缺乏 临床感染控制结果(银水凝胶涂层)或刺激性/不适感(呋喃西林) 审判。最近的研究表明，生物膜的形成是由蛋白质沉积引起的。 这也会引起炎症和免疫反应。因此，下一代 技术既需要抗微生物功能，也需要抗免疫反应能力 以产生控制感染的复合效果。我们公司发明了一种新的 可经济高效地混合到现有硅中的聚合物添加剂产品(HaloAddTM) 橡胶树脂生产硅胶导尿管，可提供多种功能，如 抗菌、抗蛋白黏附、抗炎。这一阶段的努力是为了 回答关于这种方法的一些基本的可行性、有效性和安全性问题 体外和体内检测方法。我们提出三个具体目标： 1)优化聚合物 开发卤代加成共混型硅橡胶配方的合成和共混参数 最大的抗菌防污效果；2)测定尿路病原体附着 卤代硅胶管的预防、生物相容性和稳定性；3)在 在体内，HaloAdd导管提供了可测量的抗炎和抗生物被膜结果 小鼠感染模型。第一阶段工作的成功将为FDA奠定基础 允许进行人体试验。

Abstract: Catheter-associated urinary tract infection (CAUTI) is the most common type of healthcare-associated infection, however currently there is no effective technology to address the problem. Antimicrobial (anti-biofilm) functionality on the catheter surface is an important field that has gained a lot of attention; however, commercial applications are limited due to a lack of infection control outcomes (silver-hydrogel coating) or irritation/discomfort (nitrofural) in clinical trials. Recent research has now shown that biofilm formation is caused by protein deposition which will also cause inflammation and immunoreaction. Therefore, the next generation technology needs both antimicrobial functionalities along with anti-immunoreaction capabilities to produce a compound effect for infection control. Our company invented a new category of polymer additive product (HaloAddTM) that can be cost-effectively blended into existing silicon rubber resins to produce silicone urinary catheters that can provide multiple functions such as antimicrobial, anti-protein adhesion and anti-inflammation. This phase I effort is geared towards answering some basic feasibility, efficacy, and safety questions about this approach using both in vitro and in vivo testing methods. We propose three specific aims: 1) optimize polymer synthesis and blending parameters to develop HaloAdd-blended silicone rubber formulas with maximum antimicrobial and anti-fouling efficacy; 2) determine uropathogen attachment prevention, biocompatibility, and stability of HaloAdd-blended silicone tubes; 3) demonstrate in vivo that HaloAdd catheter provides measurable anti-inflammation and anti-biofilm outcomes in a mouse infection model. Success with this phase I effort will lay the groundwork for FDA clearance for human trials.