Advanced Bactericidal Urinary Catheters Based on Electromodulated Nitric Oxide Release

描述（由申请人提供）：我们提出了一种全新的、低成本的和耐用的杀菌性100%硅胶导尿管，其具有> 3 - 6个月的保质期，其将利用电调节递送一氧化氮（NO）长达45 - 60天，以用作有效的抗菌剂/抗菌膜剂。第一代装置将在管腔内具有稳定的无机亚硝酸盐储库，其中亚硝酸盐可以电化学地（在表面）转化 的微丝）通过简单的Cu（II）-配体氧化还原介体转化为NO。释放的NO迅速扩散出硅胶壁，到达尿液收集腔和导管的外表面，以防止/破坏生物膜形成，从而消除导管相关的尿路感染（CITTI）。特殊的、符合ISO13485标准的20 Fr三腔100%硅胶Foley导管已由OEM公司制造，其独特的第三腔将由Biocrede Inc用于容纳和密封NO释放制剂，该制剂通过锁定在导管近端的微型10 x 10 x 20 mm功率控制器进行电化学（e-chem）激活。为了继续研究和开发这种先进的产品，我们建议：（1）研究从导管壁释放的调制NO的寿命（每天3小时，长达45 - 60天），含有我们专有的亚硝酸盐配方，以了解有效预防生物膜的阈值（奇异变形杆菌、金黄色葡萄球菌和铜绿假单胞菌或肠杆菌假单胞菌）;（2）进行保质期、扭结稳健性和灭菌研究，以了解产品在储存> 3 - 6个月后的可靠性和性能;和（3）通过ETO或伽马辐射进行灭菌研究，使包装在LLDPE袋中的组装导管达到SAL 106。尿路感染每年导致50 - 70万例医院感染，每天导管插入的累积发生率为3 - 6（10天时50%，28天时> 90%，长期100%）导致并发症，如膀胱炎、肾盂肾炎、革兰氏阴性菌血症、前列腺炎、附睾炎、尿脓毒症、败血症、睾丸炎、心内膜炎、脊椎骨髓炎、脓毒性关节炎，眼内炎，和 所有患者均为脑膜炎。这种新的电调制NO释放技术将有助于降低与RESTTI相关的成本，并仅在美国每年减少或潜在消除近10，000例死亡。Fortune Medical是一家FDA批准和ISO13485认证的公司，是Biocrede导管的OEM供应商; Biocrede（100%美国所有，安阿伯，MI）将增加专有组件，并进行质量控制、灭菌和包装。该专有技术由Biocrede Inc通过密歇根大学（安阿伯，密歇根州）的技术转让办公室进行选择。

DESCRIPTION (provided by applicant): We propose a completely new, low cost and robust bactericidal urinary 100% silicone Foley catheter with a >3-6 month shelf-life, that will utilize electromodulated delivery of nitric oxide (NO) for up to 45-60 d to serve as a potent antimicrobial/antibiofilm agent. The first generation device will possess a stable inorganic nitrit salt reservoir within on lumen, in which the nitrite can be converted electrochemically (at surface of microwire) to NO via a simple Cu(II)-ligand redox mediator. The NO released quickly diffuses out of the silicone walls onto the urine collection lumen and the catheter's outer surface to prevent/disrupt biofilm formation that will eliminate catheter-associated urinary tract infections (CAUTI). The special, ISO13485 compliant, 20Fr triple-lumen 100% silicone Foley catheter has been manufactured via an OEM company, and its unique third lumen will be employed by Biocrede Inc to contain and seal off the NO releasing formulation that is electrochemically (e-chem) activated via a miniature 10 x 10 x 20 mm power controller locked at the catheter's proximal end. To continue research and development of this advanced product, we propose: (1) to study the longevity of modulated NO release from the walls of the catheters (3 h per day for up to 45-60 d) containing our proprietary nitrite formulation to understand thresholds for effectiv biofilm prevention (Proteus mirabilis, Staphylococcus saprophyticus, and Pseudomona aeruginosa or Pseudomona Enterobacter ); (2) to perform shelf-life, kink robustness, and sterilization studies to understand product reliability and performance after >3-6 months of storage; and (3) to perform sterilization studies via ETO or Gamma radiation to reach SAL 106 of assembled catheters packaged in LLDPE bags. CAUTIs contribute to 0.5-0.7 million nosocomial hospital infections annually with a cumulative incidence of 3-6% per day of catheterization (50% at 10 days, >90% at 28 days, 100% long term) leading to complications such as cystitis, pyelonephritis, gram-negative bacteremia, prostatitis, epididymitis, urosepsis, septicemia, orchitis, endocarditis, vertebral osteomyelitis, septic arthritis, endophthalmitis, and meningitis in all patients. This new electromodulated NO release technology will help lower CAUTI related costs, and reduce or potentially eliminate near 10,000 deaths/year in the US alone. Fortune Medical, an FDA approved and ISO13485 certified company, is Biocrede's catheter OEM provider; and Biocrede (100% US owned, Ann Arbor, MI) will add the proprietary components, and perform quality control, sterilization and packaging. This proprietary technology is being optioned by Biocrede Inc through the Offices of Tech Transfer at the University of Michigan (Ann Arbor, MI).