Advanced Nitric Oxide Release Bactericidal Urinary Catheters

 描述(申请人提供)：在第一阶段，Biocrede开发了一种全新的尿路硅胶Foley导管，保质期为4.5个月，由专利聚合物配方制成，可通过释放一氧化氮(NO)有效减少导管相关性尿路感染(CAUTI)，持续&gt；2周。新技术的主要特点包括：(1)导管在37℃下连续14天以杀菌率提供NO；(2)体外数据显示，导管表面的活细菌数量(与CAUTI相关的关键细菌菌株)减少了10,000倍，并有能力在14天防止生物膜形成；(3)正在进行的研究表明，在ETO灭菌后，货架期可以很容易地延长到&gt；&gt；4.5个月之后；(4)ISO/GLP浸出试验(1-3d)和相关的细胞毒性研究(3d)和小鼠毒性研究(3d)获得了最安全的分数；(5)泌尿科医生赞扬了这种一致性、弹性和 与其他产品相比，该产品的灵活性。从导管表面释放的NO迅速从硅胶壁扩散到尿液收集管腔和导管外表面，以防止/破坏生物膜的形成，从而消除CAUTIs。CAUTIs每年造成50万-70万人的医院感染，每天导尿的累积发病率为3-6%(10天为50%，28天为90%，长期为100%)，导致患者出现膀胱炎、肾盂肾炎、革兰氏阴性菌血症、前列腺炎、附睾炎、尿毒症和败血症等并发症。这项技术将有助于降低与CAUTIs相关的成本(每次感染700美元)，并有可能防止仅在美国每年因CAUTIs而死亡的1万人中的大部分。为了继续研究和开发这一先进的产品，我们建议：(1)证明无释放导管在ETO灭菌后可以保存12个月或更长时间；(2)开发/组装受控的Allan Bradley自动化系统，以允许重复的SNAP(S-亚硝基-N-乙酰青霉胺)浸泡和瘦手术；(3)通过动物研究(兔)在7d和14d(n=8)后证明我们新的NO释放导管设计的安全性、预防CAUTI的有效性和生物相容性；(4)验证和设计可能最低的SNAP浸出；(5)在2015年为未来的510k应用进行所有GLP第三方生物兼容性研究；(6)并在2016年前获得FDA IDE批准。实现这些目标将使Biocrede能够与投资者合作，为我们的510k(从头开始)应用程序资助未来的临床第一阶段试点研究和临床第二阶段最终研究。获得FDA批准和ISO13485认证的财富医疗公司是Biocrede的导管OEM供应商；Biocrede(美国100%拥有，Ann Arbor，MI)将添加专有组件(SNAP浸渍技术)，并执行质量控制、灭菌和包装。这项专利技术由Biocrede Inc.通过密歇根大学(密歇根大学安娜堡)的技术转移办公室获得许可。

 DESCRIPTION (provided by applicant): In Phase I, Biocrede developed a completely new urinary tract silicone Foley catheter with a >4.5 month shelf-life, made from a proprietary polymeric formulation to effectively reduce catheter-associated urinary tract infections (CAUTI) via nitric oxide (NO) release for >2 weeks. Key features of the new technology include: (1) catheters continuously deliver NO at bactericidal rates for >14 d at 37°C; (2) In vitro data demonstrate a 10,000 fold reduction of live bacteria counts (for key bacteria strains associated with CAUTI) on catheter surfaces and ability to prevent biofilm formation at 14 days; (3) ongoing study shows that shelf- life can easily be extended beyond >>4.5 months after ETO sterilization; (4) ISO/GLP leaching tests (1-3 d) and associated toxicity studies on cells (3 d) and in mice (3 d) received the safest scores possible; and (5) urologists praised the consistency, elasticity, and flexibility of the product compared to others. The NO released from the surfaces of the catheter quickly diffuses out of the silicone walls into the urine collection lumen and from the catheter's outer surface to prevent/disrupt biofilm formation that will eliminate CAUTIs. 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, etc., in patients. This technology will help reduce the costs associated with CAUTIs ($700 per infection) and potentially prevent most of the 10,000 deaths/year due to CAUTIs in the US alone. To continue research and development of this advanced product, we propose to: (1) prove that NO releasing catheters can be stored for 12 months or more after EtO sterilization; (2) develop/assemble a controlled Allan Bradley automated system to allow repeatable SNAP (S-nitroso-N-acetyl-penicillamine) impregnation and lean operation efforts; (3) prove the safety, CAUTI prevention efficacy, and biocompatibility of our new NO releasing Foley catheter design via animal studies (rabbits) after 7 d and 14 d (n=8 each); (4) verify and design for lowest possible SNAP leaching; (5) perform all of the required GLP third party biocompatibility studies for future 510k application in 2015; (6) and receive the FDA IDE approval by 2016. Achieving these goals will allow Biocrede to work with investors to fund a future clinical Phase I pilot study, and clinical Phase II final study for our 510k (De novo) applications. 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 (SNAP impregnation technology), and perform quality control, sterilization and packaging. This proprietary technology is being licensed by Biocrede Inc. through the Offices of Tech Transfer at the University of Michigan (Ann Arbor, MI).