PREVENTION OF BIOFILMS IN MEDICAL DEVICES

预防医疗器械中的生物膜

• 批准号: 6694275
• 负责人: Saraswathi Mandapati
• 金额: $ 10万
• 依托单位: ALTUS PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2004-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6694275
• 关键词: SDS polyacrylamide gel electrophoresis; bacterial disease; bioassay; biofilm; biomedical equipment; biotechnology; blood transfusion; catheterization; crosslink; crystallization; disease /disorder prevention /control; drug delivery systems; enzyme activity; gel filtration chromatography; growth inhibitors; high performance liquid chromatography; implant; infection; infrared spectrometry; microorganism growth; orthopedics; peptidases; prosthesis; streptokinase; surface coating; transplantation

DESCRIPTION (provided by applicant): Design of new efficient drug delivery systems for proteins is one of the major themes of modern biotechnology and biopharmaceutical industry. We found that cross-linked enzyme crystals (CLECs) show remarkable stability at various pHs, on storage, against proteolysis and organic solvents. These properties make them ideal for treatment against biofilm formation on medical devices /implants such as urethral catheters, ureteric and prostatic stents, penile and testicular implants, artificial urinary sphincters, prostheses for hip and knee replacements, shunts for hydrocephalus, vascular grafts, heart valves, vascular access devices, voice prostheses, etc. In addition, the CLECS can be used for the prevention of blood clot formation, for example, in venous catheters. The CLEC agent will be used to coat the medical devices for the prevention of formation of bacterial biofilms on these devices as well as the prevention of blood clots. The biofilms form on the above medical devices by colonization of bacteria embedded in a matrix, which become resistant to commonly used antibiotics. In this Phase I study, we propose to develop two prototypes of CLECs of enzyme - Serratiopeptidase and Streptokinase for prevention of biofilms by Pseudomonas aeruginosa and Staphylococcus aureus microorganisms. The coating will prevent the adherence of these bacteria to medical devices. Currently, there are more than 850,000 case infections associated with aid devices annually in the United States. These may be associated with as many as 100,000 deaths per year. The CLECs of Serratiopeptidase and Streptokinase have enormous commercial potential over the currently available treatment for the prevention of contamination of medical devices by minimizing the need for replacement once they are implanted. The CLECs of Serratiopeptidase and Streptokinase will also be important in preventing biofilm-related infections which are resistant to commercially available antibiotics.

描述（由申请人提供）： 设计新型高效的蛋白质药物递送系统是现代生物技术和生物制药行业的主题之一。我们发现交联酶晶体 (CLEC) 在各种 pH 值、储存、蛋白水解和有机溶剂下均表现出显着的稳定性。这些特性使其成为治疗医疗器械/植入物上生物膜形成的理想选择，例如导尿管、输尿管和前列腺支架、阴茎和睾丸植入物、人工尿道括约肌、髋关节和膝关节置换假体、脑积水分流器、血管移植物、心脏瓣膜、血管通路装置、发声假体等。此外，CLECS 还可以 可用于预防血凝块形成，例如在静脉导管中。 CLEC 剂将用于涂覆医疗设备，以防止这些设备上形成细菌生物膜以及防止血栓。通过嵌入基质中的细菌定植，在上述医疗设备上形成生物膜，这些细菌对常用抗生素产生抗药性。在这项第一阶段研究中，我们建议开发两种酶的 CLEC 原型 - 沙雷肽酶和链激酶，用于预防铜绿假单胞菌和金黄色葡萄球菌微生物的生物膜。涂层将防止这些细菌粘附在医疗器械上。目前，美国每年有超过 85 万例与援助设备相关的感染病例。这些可能与每年多达 100,000 人的死亡有关。与目前可用的预防医疗器械污染的治疗方法相比，沙雷肽酶和链激酶的 CLEC 通过最大限度地减少植入后的更换需求，具有巨大的商业潜力。沙雷肽酶和链激酶的 CLEC 对于预防对市售抗生素具有抗药性的生物膜相关感染也很重要。