Improvement and validation of the Spring System for Permanent Relief of Urinary Obstruction related to Benign Prostatic Hyperplasia (BPH)

摘要 良性前列腺增生（BPH）是下尿路梗阻症状的最常见原因， 男人随着年龄的增长，前列腺逐渐增大，它阻碍了尿液从膀胱流出，导致 尿急、尿频、尿急、尿痛。在Zenflow，我们开发了Spring系统， 由单线镍钛（镍钛诺）弹簧圈植入物组成，设计用于永久缓解BPH相关的尿 阻塞，和一个灵活的经尿道输送系统，包括一个膀胱镜与内置的可视化。我们 开发此解决方案，以满足长期以来对安全、有效、经济高效、基于办公室的临床需求 BPH治疗在一次手术中提供持久的症状缓解，无副作用。该装置旨在 改进了以前的技术，如支架和前列腺尿道提升装置。2014年至 2017年，我们开发了第一代Spring系统，并成功完成了临床前工作，包括 尸体和慢性动物研究，然后是首次人体研究。2017年，我们获得了NIH SBIR II期 格兰特.该项目涉及改进设计的开发，以提高临床安全性、有效性和易用性 的使用。这个II期项目的目标是，结合正在进行的试点临床试验，准备Zenflow 美国关键IDE研究。虽然该项目的目标是成功的，但临床试验揭示了机会 进一步改进弹簧系统，我们相信这将导致一个更安全，更可靠的 手术达到了一个新的前沿的有效性，也将扩大范围的解剖 系统可以处理的配置。这些改进分为两类，我们提供测试 目前的拨款建议：在具体目标1中，我们将改进植入物和输送系统， 有效的程序，可以治疗更广泛的患者，并在具体目标2，我们将提高我们的 专有的一次性膀胱镜，使更好的可视化，并允许泌尿科医生放置植入物更多 准确和自信。接下来，在具体目标3中，我们将验证上述所有改进，我们将 在尸体上测试完整的弹簧系统，以证明弹簧系统在模拟使用中的功能 泌尿科医生在完成所有植入和输送后，将在第1年年底对两具尸体进行系统测试 目标1中描述的系统工作，然后在完成所有范围开发后，在第2年底再进行两项工作 目标2.这两项研究的成功完成将代表我们第二阶段工作的完成。我们将 将Aim 1植入物工作的结果纳入我们的美国关键IDE研究。Aim 2范围改进 将纳入后续临床研究。虽然我们专门开发了Spring Scope来放置 弹簧植入物，它可用于部署植入物，以治疗尿道狭窄或 膀胱疼痛综合征、递送药物或能量以治疗BPH相关的LUTS、前列腺癌或其他 条件我们将继续探索这些可能性，并为替代应用程序提交知识产权。

ABSTRACT Benign Prostatic Hyperplasia (BPH) is the most common cause of obstructive lower urinary tract symptoms in men. As the prostate progressively enlarges with age, it obstructs the flow of urine from the bladder, leading to urinary straining, frequency, urgency, and nocturia. At Zenflow, we have developed the Spring System, which consists of a single-wire nickel titanium (nitinol) coil implant designed to permanently relieve BPH-related urinary obstruction, and a flexible transurethral delivery system that includes a cystoscope with built-in visualization. We developed this solution to meet the long-standing clinical need for a safe, effective, cost-efficient, office-based BPH therapy that provides durable symptom relief in a single procedure without side effects. The device aims to improve upon previous technologies such as stents and the prostatic urethral lift device. Between 2014 and 2017, we developed the first-generation Spring System and successfully completed preclinical work including cadaver and chronic animal studies, then first-in-man studies. In 2017, we were awarded a Phase II NIH SBIR grant. This project involved development of a refined design to improve clinical safety, effectiveness, and ease of use. The goal of this Phase II project was, in conjunction with ongoing pilot clinical trials, to prepare Zenflow for a US pivotal IDE study. While the aims of this project were successful, clinical testing revealed opportunities for further improvements to the Spring System, which we believe will result in an even safer and more reliable procedure that reaches a new frontier in effectiveness, and will also expand the range of anatomical configurations that the system can treat. These improvements fall into two categories which we offer to test under the current grant proposal: in Specific Aim 1 we will improve the implant and delivery system to yield a more effective procedure that can treat a broader range of patients, and in Specific Aim 2 we will improve our proprietary single-use cystoscope to enable better visualization and allow urologists to place the implant more accurately and confidently. Next, in Specific Aim 3 we will validate all improvements described above, we will test the full Spring System in cadavers to demonstrate functionality of the Spring System in simulated use by a urologist. The system will be tested on two cadavers at the end of year 1 after completing all implant and delivery system work described in Aim 1, then two more at the end of year 2 after completing all scope developments in Aim 2. Successful completion of both of these studies will represent completion of our Phase II work. We will incorporate the results of the Aim 1 implant work into our US pivotal IDE study. The Aim 2 Scope improvements will be incorporated into later clinical studies. While we developed the Spring Scope specifically to place the Spring Implant, it could be used for deployment of implants to treat conditions such as urethral strictures or painful bladder syndrome, delivery of drugs or energy to treat BPH-related LUTS, prostate cancer, or other conditions. We will continue to explore these possibilities and file intellectual property on alternative applications.