Tethered liquid perfluorocarbon coating for preventing urinary catheter colonization

项目摘要 尿路感染（UTIs）是全球最常见的感染之一，影响约1.5亿人 每年，导尿管（UC）是UTI的主要原因。有> 100万个导管相关 美国每年发生尿路感染（CAUTI），治疗费用超过3.5亿美元/年。 未经治疗的尿路感染可导致肾脏和血液感染，败血症，甚至死亡。虽然抗生素 治疗可以成功治疗尿路感染并降低脓毒症的风险，但通常使用不适当的抗生素 并促进抗生素耐药性和艰难梭菌结肠炎的风险。因此，更好的方法是 需要 FreeFlow Medical Devices（FreeFlow）正在优化和商业化系留液体全氟化碳（TLP） 医疗器械上的涂层。该SBIR项目的目标是验证TLP涂层UC （TLP-UC）将抵抗病原体的粘附和随后的生物膜形成，这是导致 我的天我们的长期目标是通过降低UC的发生率来改善需要UC的患者的结局。 感染引起的并发症。我们的全憎性涂层可阻止所有生物成分的粘附 （细菌、真菌、血液成分、尿液）到医疗器械的表面，通过固定薄 高度惰性和生物相容的全氟化液体层。我们优化的涂层技术结合了 借助化学气相沉积技术在各种表面上形成薄的含氟聚合物层。 第一阶段提案的目的是获得我们的TLP-UC将抵抗 在生理性尿流条件下，导致尿路感染的病原体粘附≥30天。虽然 我们以前实现了这些目标，针对负责血液感染的病原体， 静脉导管（CVC）、CVC和UC之间的固有差异及其生理暴露 这意味着确保这些属性保留在UC中至关重要。第一阶段申请的目标是 将通过研究以下具体目标来实现。目的1：测量TLP涂层与 导尿管，并评估抑制病原体定植的能力。目的2：确定TLP的能力- 涂覆UC以承受生理流动条件和病原体定殖。目标3：确定 TLP包被的UC可耐受来自人类样本的多种CITTI病原体的定殖。一旦证明 概念已经获得，我们将进展到cGMP生产和FDA推荐的第二阶段 生物相容性测试准备上市前批准。

PROJECT SUMMARY Urinary tract infections (UTIs) are one of the most common infections worldwide, effecting ~150 million people annually, and urinary catheters (UCs) are a major cause of UTIs. There are >1 million Catheter-Associated Urinary Tract Infections (CAUTIs) each year in the US, with treatment costs exceeding $350 million/year. Untreated CAUTIs can lead to kidney and bloodstream infections, sepsis, or even death. While antibiotic treatment can successfully treat CAUTIs and reduce the risk of sepsis, inappropriate antibiotic use is common and promotes antimicrobial resistance and risk of Clostridium difficile colitis. Thus, better approaches are needed FreeFlow Medical Devices (FreeFlow) is optimizing and commercializing tethered liquid perfluorocarbon (TLP) coatings on medical devices. The goal of this SBIR project is to validate the hypothesis that TLP-coated UCs (TLP-UCs) will resist the adhesion of pathogens and subsequent biofilm formation that are responsible for CAUTI. Our long-term goal is to improve outcomes for patients requiring UCs by reducing the rate of complications caused by infection. Our omniphobic coating stops the adhesion of all biological components (bacteria, fungi, blood components, urine) to the surface of medical devices through the immobilization of a thin layer of highly inert and biocompatible perfluorinated liquid. Our optimized coating technology incorporates a thin fluoropolymer layer on various surfaces with the help of chemical vapor deposition technique. The objective of this phase I proposal is to obtain the proof of concept that our TLP-UCs will resist the adhesion of pathogens responsible for CAUTI for ≥30 days under physiological urine flow conditions. Although we previously achieved these goals against the pathogens responsible for bloodstream infections with central venous catheters (CVC), the inherent differences between CVC and UC and their physiological exposure mean that it is critical to ensure that these properties are retained in UCs. The goals of this phase I application will be achieved by investigating the following Specific Aims. Aim 1: Measure adherence of the TLP coating to urinary catheters and assess the ability to inhibit pathogen colonization. Aim 2: Determine the ability of TLP- coated UC to withstand physiological flow conditions and pathogen colonization. Aim 3: Determine the ability of TLP-coated UC to withstand colonization by diverse CAUTI pathogens from human specimens. Once proof of concept has been obtained, we will progress to Phase II for cGMP manufacturing and FDA-recommended biocompatibility testing ready for premarket approval.