Dual Function Catheter to Prevent Thrombus and Infection

预防血栓和感染的双功能导管

• 批准号: 8249463
• 负责人: Jennifer Ann Neff
• 金额: $ 98.03万
• 依托单位: ALLVIVO VASCULAR, INC.
• 依托单位国家: 美国
• 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/8249463
• 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; public health relevance; research clinical testing; success; ultraviolet irradiation

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批准所需的临床前测试。该产品将通过：（1）提供对生物膜和血栓具有抗药性的双重功能涂层的3个主要未满足需求，（2）结合抗菌技术不会刺激抗生素耐药细菌的生长，以及（3）改善相对现有产品的抗生素活性持续时间。涂层基于新型抗蛋白抗块共聚物和抗菌肽的组合。涂层将通过将肽与两种模式（通过柔性系绳和通过捕集）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，则可以保持抗菌活性。以这种方式制备的抗菌肽的一层应该是安全，功能性和持久的。该技术的一个关键特征是，它通过一种与临床抗生素的多层机制杀死细菌，并且不太可能引起细菌发展抗性。在建议的支持期间，将优化涂料组成和施用过程。将评估涂层导管对临床相关细菌，耐用性和机械性能的涂料功效，以确保开发的涂层过程不会改变导管的必要机械性能。将在良好的制造实践（GMP）下生产涂料组件，并将开发和实施GMP制造工艺，以生产完全涂层和组​​装导管。 FDA批准涂层导管所需的临床前测试也将完成。在此开发计划的结尾，公司将准备提交510K申请，并计划开始批准临床测试。这项工作的结果将对向急性和末期肾脏疾病血液透析患者提供优质护理的能力产生重大影响，并将降低由于感染引起的发病率和死亡率的风险。这也将对控制这些患者种群的快速增长成本的能力产生重大影响，通过预防昂贵的导管相关的血流感染。 公共卫生相关性：抗菌涂料是预防医疗器械相关感染的关键，这是高发病和死亡率，更长的住院时间以及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，而不会损害有限的临床抗生素疗法的疗效。预计这项技术将大大降低急性和慢性血液透析患者的发病率和死亡率，并通过预防感染来帮助控制其治疗成本。该研究计划可能有可能解决医疗设备上生物膜形成的基本问题的解决方案，这将是朝着负责任的感染控制迈出的重要一步。