PREVENTION OF BIOFILMS IN MEDICAL DEVICES

描述(申请人提供)：设计新型高效的蛋白质药物输送系统是现代生物技术和生物制药工业的主要主题之一。我们发现，交联酶晶体(CLECs)在不同的PHS、储存、抗蛋白水解性和有机溶剂中表现出显著的稳定性。这些特性使其成为治疗医疗设备/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、人造尿括约肌、髋关节和膝关节置换的假体、脑积水的分流术、血管移植物、心脏瓣膜、血管通路装置、语音假体等。此外，CLEC还可用于防止血液凝块的形成，例如静脉导管。CLEC试剂将被用于涂覆医疗器械，以防止这些器械上形成细菌生物膜，以及防止血液凝块。这些生物膜通过植入基质中的细菌在上述医疗器械上形成定植，这些细菌对常用的抗生素产生抗药性。在这项第一阶段的研究中，我们建议开发两种CLECs的原型--沙雷菌肽酶和链激酶，以防止铜绿假单胞菌和金黄色葡萄球菌的生物被膜。这种涂层将防止这些细菌附着在医疗设备上。目前，美国每年有超过85万例与援助设备有关的感染病例。这可能与每年多达10万人的死亡有关。与现有的预防医疗器械污染的治疗方法相比，沙雷多肽酶和链激酶的CLECs具有巨大的商业潜力，因为它将医疗器械植入后的更换需求降至最低。沙雷多肽酶和链激酶的CLECs在预防对商业抗生素具有耐药性的生物被膜相关感染方面也将是重要的。

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.