Dual Function Catheter to Prevent Thrombus and Infection

描述（由申请人提供）：本工作的目的是完成新型抗菌急性血液透析导管的开发，并进行FDA批准所需的临床前试验。该产品将通过以下方式解决静脉导管的3个主要未满足需求：（1）提供抗生物膜和血栓的双功能涂层，（2）采用不会刺激抗生素耐药菌生长的抗菌技术，以及（3）相对于现有产品，改善抗菌活性的持续时间。该涂层基于新型抗蛋白质嵌段共聚物和抗微生物肽的组合。将通过以两种模式（通过柔性系链和通过包埋）将肽结合到表面来产生涂层。最近的研究表明，这是一种基于肽的行为的可行方法，并表明如果保持足够的溶剂可及性和分子移动性，则当结合到表面时可以保持抗微生物活性。以这种方式制备的抗菌肽层应该是安全的、功能性的和持久的。该技术的一个关键特点是，它通过一种多层次的机制杀死细菌，这种机制与临床抗生素的机制有着根本的不同，不太可能导致细菌产生耐药性。在拟议的支持期间，将优化涂料成分和施工工艺。将评价涂层导管对临床相关细菌菌株的涂层有效性、耐久性和机械性能，以确保开发的涂层工艺不会改变导管的必要机械性能。涂层组件将按照药品生产质量管理规范（GMP）生产，并将开发和实施GMP生产工艺，用于生产完全涂层和组装的导管。还将完成FDA批准涂层导管所需的临床前试验。在这个开发项目结束时，该公司将准备提交510 k申请，并计划开始批准后的临床试验。这项工作的结果将对向急性和终末期肾病血液透析患者提供优质护理的能力产生重大影响，并将降低他们因感染而发病和死亡的风险。它还将对通过预防昂贵的导管相关血流感染来控制治疗这些患者群体的快速增长的成本的能力产生重大影响。 公共卫生相关性：抗菌涂层是预防医疗器械相关感染的关键，这是高发病率和死亡率、较长住院时间和不必要的治疗费用的原因。该项目旨在开发一种新的抗菌涂层技术，并将其应用于生产抗菌血液透析导管，该导管将防止生物膜，而不会影响有限的临床抗生素库的功效。该技术有望大幅降低急性和慢性血液透析患者的发病率和死亡率，并通过预防感染帮助控制治疗成本。这项研究计划将有可能解决医疗器械上生物膜形成的基本问题，并将成为负责任的感染控制的重要一步。

DESCRIPTION (provided by applicant): The objective of this work is to complete development of a novel antibacterial, acute hemodialysis catheter and conduct the preclinical testing required for FDA approval. This product will address 3 major unmet needs for intravenous catheters by: (1) providing dual function coatings that are resistant to both biofilm and thrombus, (2) incorporating antimicrobial technology that will not stimulate the growth of antibiotic resistant bacteria, and (3) improving the duration of antimicrobial activity relative to existing products. The coating is based on a combination of a novel protein resistant block copolymer and an antimicrobial peptide. Coatings will be produced by binding the peptide to surfaces in two modes (via a flexible tether and via entrapment). Recent studies indicate that this is a viable approach based on the peptide's behavior and suggests antimicrobial activity can be maintained when bound to a surface if sufficient solvent accessibility and molecular mobility are preserved. A layer of the antibacterial peptide prepared in this way should be safe, functional, and long-lasting. A key feature of this technology is that it kills bacteria through a multi-tiered mechanism that is fundamentally different from that of clinical antibiotics and is unlikely to cause bacteria to develop resistance. During the proposed period of support, the coating composition and application process will be optimized. Coated catheters will be evaluated for coating efficacy against clinically relevant bacteria strains, durability and mechanical properties to ensure that the coating process developed does not alter the necessary mechanical properties of the catheter. Coating components will be produced under Good Manufacturing Practice (GMPs) and a GMP manufacturing process will be developed and implemented for production of the fully coated and assembled catheter. Preclinical testing required for FDA approval of the coated catheters will also be completed. At the end of this development program, the company will be ready to submit a 510k application and plan to begin post approval clinical testing. The results of this work will have a significant impact on the ability to deliver quality care to both acute and end stage renal disease hemodialysis patients and will decrease their risks of morbidity and mortality due to infections. It will also have a significant impact on the ability to control the rapidly growing cost of treating these patient populations by preventing costly catheter related blood stream infections. PUBLIC HEALTH RELEVANCE: Antibacterial coatings are key to the prevention of medical device related infections, which are a cause of high morbidity and mortality, longer hospital stays, and unnecessary treatment costs. This project aims to develop a new antimicrobial coating technology and apply it to produce an antimicrobial hemodialysis catheter that will prevent biofilms without compromising the efficacy of the limited arsenal of clinical antibiotics. This technology is expected to substantially decrease morbidity and mortality for acute and chronic hemodialysis patients as well as help contain their treatment cost by preventing infections. This research program will potentially yield a solution to the fundamental problem of biofilm formation on medical devices and will be an important step toward responsible infection control.