Internal Polymeric Vessel Occluder for Temporary Vascular Occlusion of the Kidney

描述（由申请人提供）：Pluromed，Inc. NIH SBIR第一阶段资助申请内部聚合物血管封堵器用于部分肾切除术期间暂时性肾血管闭塞项目摘要/摘要保留肾单位的手术在肾肿块的治疗中变得越来越常见。随着经验的增加，控制术中肾出血的必要性越来越重要。这种需求被泌尿外科手术向机器人和微创技术发展的趋势所放大，即使是少量的血液也会严重限制可视性。因此，已经开发了许多技术来实现止血，包括传统缝合修复、组织封闭剂、射频消融、激光消融、水切割和微波组织凝固。 Pluromed开发了一种生物相容性凝胶，其中血管充满凝胶并被凝胶堵塞。凝胶的工作原理是基于聚合物的反向热敏特性。在低温下，聚合物溶液是液体。当温度升高到体温时，溶液的粘度迅速增加几个数量级，达到硬凝胶的稠度。冷却闭塞部位，例如通过施加冰，将粘度降低回液体的粘度，将凝胶溶解在血液中并重建血流。该凝胶已开发用于吻合术，如非体外循环旁路手术（OPCAB）、血液透析通路和胫骨吻合术。它已经被证明是非常温和的工作，既不损害也不改变动脉壁的生化组成，如通过测量填充和打开血管后的微血管反应性所证明的。该I期申请的建议是将相同的原则应用于保留肾单位的手术。在这种方法中，通向患病肾脏的肾动脉被注入反向热敏凝胶。这已被证明会导致肾实质内血流停止。看起来，在适当的注射速率下，聚合物向下游流动以闭塞循环的动脉侧和静脉侧上的小的肾内血管。这产生了一个完全无血的手术野，允许快速切除。大约20分钟后，血流逐渐恢复，对肾脏没有明显的不良后果。如果需要，可以通过冷却肾脏来加速血流的回流。初步的短期体内实验表明了这种方法的可行性。然而，在这些初步实验中使用的聚合物具有低于固体器官的最佳转变温度。在实体器官中，如肾脏，手术过程中的温度可能高于暴露的动脉，因为该公司有更多的实验经验。对于实体器官应用，具有较高转变温度的聚合物溶液可能优于本发明制剂的上级。此外，需要进行更广泛的动物研究，以确定注射速率/体积与预期下游缺血时间之间的关系。还需要开发一种注射系统，该注射系统不会由于需要长时间的动脉解剖或由于需要额外的手术来修复注射部位处的动脉而过度地增加手术时间。这些参数的描述将允许在II期进行慢性动物实验，并为随后的临床应用提供明确的途径，John A.利伯蒂诺说，主席的泌尿科在Lahey诊所医疗中心。Pluromed公司NIH SBIR I期资助申请：用于肾部分切除术中暂时性肾血管闭塞的内部聚合物血管闭塞器

DESCRIPTION (provided by applicant): Pluromed, Inc. NIH SBIR Phase I Grant Application Internal Polymeric Vessel Occluder for Temporary Vascular Occlusion of the Kidney During Partial Nephrectomy Project Summary/Abstract Nephron-sparing surgery has become more common for the treatment of renal masses. With increasing experience, the need to control intraoperative renal bleeding is increasingly significant. This need is amplified by the trend in urologic surgery towards robotic and minimally invasive techniques where visibility can be severely limited by even small volumes of blood. As a result, many techniques have been developed to achieve hemostasis, including conventional suture repair, tissue sealants, radiofrequency ablation, laser ablation, water dissection, and microwave tissue coagulation. Pluromed has developed a biocompatible gel in which the blood vessel is filled with and occluded by the gel. The gel's working principle is based on the reverse thermosensitive properties of the polymer. At low temperatures, the polymeric solution is a liquid. As the temperature increases to body temperature, the viscosity of the solution rapidly increases several orders of magnitude to the consistency of a hard gel. Cooling the occlusion site, for example by applying ice, lowers the viscosity back to that of a liquid, dissolving the gel in blood and reestablishing blood flow. The gel has been developed for applications in anastomosis such as Off-Pump Bypass surgery (OPCAB), hemodialysis access, and tibial anastomosis. It has been shown to work very gently, neither compromising nor changing the biochemical make-up the arterial wall, as evidenced by measurements of the microvascular reactivity after filling and opening up the blood vessel. The proposal of this Phase I application is to apply the same principle to nephron-sparing surgery. In this approach, the renal artery leading to the diseased kidney is infused with the reverse thermosensitive gel. This has been shown to lead to cessation of blood flow within the renal parenchyma. It appears that, with the appropriate injection rate, the polymer flows downstream to occlude small, intra-renal vessels on both the arterial and venous sides of the circulation. This produces a completely bloodless surgical field, allowing speedy resection. After about 20 minutes the flow gradually resumes, with no apparent adverse consequences to the kidney. Return of blood flow may then be accelerated, if necessary, by cooling the kidney. Initial short-term in-vivo experiments indicate the feasibility of this approach. However, the polymer used in these preliminary experiments has a lower than optimal transition temperature for a solid organ. In a solid organ, such as the kidney, temperatures during the surgery may be higher than in exposed arteries where the company has greater experimental experience. A polymer solution with a higher transition temperature may be superior to the present formulation for solid organ applications. Furthermore, a more extensive animal study is needed to ascertain the relationship between rate/volume of injection and the expected downstream ischemic time. It is also necessary to develop an injection system that does not unduly increase the procedural time by requiring a long dissection of the artery or by requiring additional surgery to repair the artery at the injection site. Delineation of these parameters will allow for chronic animal experiments in Phase II and a clear path forward to subsequent clinical application with the declared involvement of Dr. John A. Libertino, Chairman of the Department of Urology at Lahey Clinic Medical Center. Pluromed, Inc. NIH SBIR Phase I Grant Application Internal Polymeric Vessel Occluder for Temporary Vascular Occlusion of the Kidney During Partial Nephrectomy