Dual Function Catheter to Prevent Thrombus and Infection

预防血栓和感染的双功能导管

基本信息

批准号：
8058437
负责人：
Jennifer Ann Neff
金额：
$ 99.94万
依托单位：
ALLVIVO VASCULAR, INC.
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-20 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8058437
关键词：
Achievement Acute Address Agreement Anti-Bacterial Agents Antibiotic Resistance Antibiotics Bacteria Behavior Binding Blood Catheters Chemicals Chronic Clinical Clinical Trials Contracts DNA Sequence Rearrangement Development Device Approval Devices Dimensions End stage renal failure Ensure Exposure to Goals Growth Health Care Costs Hemodialysis Infection Infection Control Infection prevention Intravenous Lead Length of Stay Manufacturer Name Marketing Mechanics Medical Device Methods Microbial Biofilms Molecular Morbidity - disease rate Patient Care Patients Peptides Performance Phase Polyethylene Glycols Polyurethanes Positioning Attribute Preclinical Testing Prevention Process Product Approvals Production Program Development Property Proteins Quality of Care Recording of previous events Relative (related person)Research Resistance Resistance development Risk Sales Small Business Innovation Research Grant Solutions Solvents Source Sterilization Stream Structure Surface Surface Properties Technology Thrombus Treatment Cost Validation Work antimicrobial antimicrobial drug antimicrobial peptide bacterial resistance base clinically relevant combat comparative efficacy copolymer cost design experience flexibility improved irradiation killings manufacturing process meetings mortality novel patient population polybutadiene prevent process optimization programs research clinical testing success ultraviolet irradiation

项目摘要

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.

描述（由申请人提供）：这项工作的目标是完成新型抗菌、急性血液透析导管的开发，并进行 FDA 批准所需的临床前测试。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) 结合不会刺激抗生素耐药细菌生长的抗菌技术，以及 (3)相对于现有产品，提高抗菌活性的持续时间。该涂层基于新型抗蛋白嵌段共聚物和抗菌肽的组合。涂层将通过将肽以两种模式（通过柔性系绳和通过包埋）结合到表面来产生。最近的研究表明，这是一种基于肽行为的可行方法，并表明如果保留足够的溶剂可及性和分子迁移率，则在与表面结合时可以保持抗菌活性。以这种方式制备的一层抗菌肽应该是安全的、功能性的和持久的。该技术的一个关键特点是，它通过多层机制杀死细菌，与临床抗生素的机制根本不同，并且不太可能导致细菌产生耐药性。在建议的支持期内，涂料成分和施工工艺将得到优化。将评估涂层导管针对临床相关细菌菌株的涂层功效、耐用性和机械性能，以确保开发的涂层工艺不会改变导管必要的机械性能。涂层组件将根据良好制造规范 (GMP) 进行生产，并将开发和实施 GMP 制造工艺来生产完全涂层和组装的导管。 FDA 批准涂层导管所需的临床前测试也将完成。在此开发计划结束时，该公司将准备好提交 510k 申请并计划开始批准后的临床测试。这项工作的结果将对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。公共健康相关性：抗菌涂层是预防医疗器械相关感染的关键，这些感染是导致高发病率和死亡率、更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，该导管可防止生物膜的形成，同时又不影响有限的临床抗生素的功效。该技术预计将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其治疗成本。该研究计划将有可能解决医疗器械上生物膜形成的根本问题，并将成为负责任的感染控制的重要一步。