Image-Guided Transurethral HIFU for Genitourinary Therapy

摘要 女性压力性尿失禁(SUI)是盆底顺应性增加，导致 尿路压力降低，通常是通过分娩，在腹部时表现为尿漏 紧张。穗对妇女的健康有重大影响，包括与增加的水平有关 抑郁症。治疗方法仅限于带状植入物的侵入性外科插入，这限制了 尿路的活动度。在尿路周围组织内注射扩张剂是一种长期有效的方法，但 临时治疗。药品相对较新，价格高得令人望而却步，而且没有记录 可能会产生长期疗效和不良反应。大约有1400万妇女被降级到 一整天都穿着吸收垫或尿布的治标方法。存在大量的临床需求 以一种非侵入性的方法替代传统的外科手术方法，并承诺减少发病率和恢复 时间、更快的程序时间和更低的成本。微创热疗的临床研究近况 技术已经证明，对骨盆组织进行有针对性的热修改和硬化可以减少 SUI的症状。这些技术显示出了希望，但它们比目前的外科手术更具侵入性 选项和效率较低。我们的第二阶段发育研究显示，体内结果令人鼓舞，表明 我们创新的基于治疗性超声导管的非侵入性技术可以有效地传递热量 在不损伤周围组织(阴道和尿路)的情况下治疗盆内筋膜靶组织 墙)，基于组织病理学分析，具有提供动态空间控制的能力 有选择的加热模式、良好控制的径向热渗透和快速的治疗时间。相比之下， 与现有的热方法相比，我们的第二阶段结果清楚地表明了技术的重大进步 以及用于治疗SUI的方法，承诺更准确和彻底地定向热诱导 胶原蛋白再生，保护关键的非靶向组织(例如，尿道和阴道粘膜)，短 手术时间，从而增加了更多SUI患者的可及性。这样做的目的是 第二阶段计划是设计-冻结我们的治疗敷贴器设计，然后与我们的GLP进行体内研究 超声波SUI导管和FDA 510(K)清除了TheraVision®系统的数据，以支持后续临床 在FDA的指导下进行研究，并围绕该技术进一步建立更多强大的知识产权。 将进行市场分析，以制定导致商业化的战略。设备设计，工作台 实验，生物热学和声学模拟，以及对两名女性的实验测试 结合工作流研究的绵羊胃肠道骨盆身体研究和体内GLP依从性研究 将进行冻结设备设计，广泛表征设备性能，并应用于 为产品定稿和临床的最终目标做准备的潜在治疗方法 实施。设备将在我们现有的符合ISO标准的质量管理体系下生产。

Abstract Stress urinary incontinence (SUI) in women is an increase of pelvic floor compliance which results in decreased urethral pressure, typically through childbirth, and presents as urine leakage during abdominal strain. SUI has significant impact on women’s health, including an association with increased levels of depression. Curative options are limited to the invasive surgical insertion of a tape implant which limits the mobility of the urethra. Bulking agents injected in the peri-urethral tissue are a longstanding effective but temporary treatment. Pharmaceuticals are relatively new, prohibitively expensive, and there is no track record of long-term efficacy and negative side effects can occur. Approximately 14 million women are relegated to the palliative approaches of wearing absorptive pads or diapers through the day. A substantial clinical need exists for a noninvasive alternative to traditional surgical approaches with the promise of less morbidity and recovery time, faster procedure time, and lower cost. Recent clinical investigations of minimally-invasive thermal techniques have demonstrated targeted thermal modification and stiffening of pelvic tissue can reduce symptoms of SUI. These techniques have shown promise, but are more invasive than the current surgical options and are less effective. Our Phase II development study showed encouraging in vivo results suggesting that our innovative therapeutic ultrasound catheter based noninvasive technology can efficiently deliver thermal therapy at the target tissue of endopelvic fascia without damaging surrounding tissue (vaginal and urethal wall), based on histopathological analysis, with demonstrated capabilities to provide dynamic spatial control of selective heating patterns, well-controlled radial thermal penetration, and fast treatment times. In comparison to existing thermal approaches, our Phase II results clearly demonstrate a significant advance in technology and approach for treating SUI with the promise of more accurate and thorough targeting of heat-induced collagen regeneration, protection of critical non-targeted tissue (e.g., urethral and vaginalmucosa), short procedure times, and thereby increasing accessibility to a larger number of SUI patients. The objective of this Phase IIB plan is to design-freeze our therapy applicator design and then conduct a GLP in-vivo study with our ultrasound SUI catheter and FDA 510(k) cleared TheraVision® system for data to support a follow-on clinical study under FDA Guidance and to further build additional strong intellectual property around the technology. Market analyses will be conducted to develop strategies leading to commercialization. Device design, bench experiments, biothermal and acoustic modeling, together with experimental testing in both human female pelvis cadaveric studies and an in-vivo GLP compliant study in ewes GU tract, combined with workflow study will be conducted to freeze device design, extensively characterize device performance, and applied to potential treatment approaches in preparation for the ultimate goal of product finalization and clinical implementation. Devices will be manufactured under our existing ISO compliant Quality Management System.