Novel Dense Hollow Fiber for Blood Gas Exchange

描述（由申请人提供）：MedArray已经成功开发了一种用于血液氧合器的新型硅膜中空纤维。我们的专利硅胶中空纤维在长期体外膜氧合（ECMO）和常规体外循环中具有巨大的商业潜力。由于ECMO可以持续1天以上，因此通常使用致密膜而不是微孔膜来防止等离子体泄漏。ECMO的膜选择是硅酮，因为它具有良好的血液相容性，并且因为它没有孔供血浆泄漏。在美国，目前FDA唯一批准用于长期应用的氧合器是美敦力的ECMO氧合器。然而，这种螺旋伤口，平板硅胶氧合器的设计可以追溯到1963年，并且有许多缺点，包括血液停滞区域，最小的对流混合，大的血液接触表面积和高血液动力学阻力。美国缺乏适合长期使用的致密膜中空纤维，这阻碍了美国制造商开发更高效的基于中空纤维的长期充氧器。我们在I期和II期的研究表明，我们的硅胶中空纤维的性能优于螺旋缠绕的硅胶膜，在气体传递和血小板趋势上与微孔膜相当。然而，我们的硅胶膜不会像微孔膜那样泄漏血浆或严重栓塞气体进入血液。此外，我们在一项为期11天的体内研究中表明，我们的膜可以执行和维持长期心肺支持的严酷条件。MedArray的硅膜中空纤维将成为美国和国外ECMO氧合器市场的有力竞争者。本提案旨在继续发展我们专有的致密膜中空纤维，同时专注于在临床氧合器中实施我们的膜的所有相关方面。具体来说，我们将根据FDA指南调查膜材料在安全性、有效性和生物相容性方面的影响，以最终满足临床使用前的要求和期望。我们还将在长期体内研究中严格测试我们的膜在氧合器中的气体传递性能和血栓形成性。最后，我们将通过评估与质量控制和降低成本相关的参数，继续改进我们的膜制造工艺，最终建立一个符合良好生产规范（GMP）的可靠和可控的工艺。这项研究和开发工作将产生一种长期血液气体传输的膜，可以取代目前可追溯到1963年的膜技术。与目前使用的长期膜相比，该膜将能够制造高效的血液氧合器，具有优越的气体传输能力，并降低致命并发症的风险。

DESCRIPTION (provided by applicant): MedArray has successfully developed under SBIR Phase I and II, a novel silicone membrane hollow fiber for use in blood oxygenators. Our patented silicone hollow fiber has great commercial potential for use in long term extracorporeal membrane oxygenation (ECMO) as well as routine cardiopulmonary bypass. Because ECMO can last more than 1 day, dense rather than microporous membranes are typically used to prevent plasma leakage. The membrane of choice for ECMO is silicone because of its excellent blood compatibility, and because it has no pores for plasma leakage. In the US, the only oxygenator currently FDA approved for use in long term applications is Medtronic's ECMO oxygenator. However, this spiral wound, flat sheet silicone oxygenator's design dates back to 1963, and has many disadvantages including areas of blood stagnation, minimal convective mixing, large blood contact surface areas, and high hemodynamic resistance. The lack of a suitable dense membrane hollow fiber for long term use in the US has prevented US manufacturers from developing a more efficient hollow fiber based long term oxygenator. Our studies in Phase I and II have shown that our silicone hollow fibers' performance is superior to the spiral wound silicone membranes, and comparable to microporous membranes in gas transfer and platelet trends. However, our silicone membrane cannot leak plasma or grossly embolize gas into the blood side like microporous membranes. Moreover, we have shown in an 11-day in-vivo study that our membrane can perform and sustain the rigors of long- term cardiorespiratory support. MedArray's silicone membrane hollow fiber will enable a strong ECMO oxygenator market contender in the US and abroad. This proposal is aimed at continuing the development of our proprietary dense membrane hollow fiber while focusing on all aspects relevant to implementing our membrane in clinical oxygenators. Specifically, we will investigate the effects of membrane materials on safety, effectiveness, and biocompatibility following FDA guidelines to ultimately meet their requirements and expectations prior to clinical use. We will also rigorously test our membrane in oxygenators for gas transfers performance, and thrombogenicity in long-term in-vivo studies. Finally, we will continue refining our membrane fabrication processes by assessing the parameters pertinent to quality control and cost reduction to ultimately establish a robust and controlled process compliant with good manufacturing practices (GMP).This research and development work will result in a membrane for long-term blood-gas transfer that can replace current membrane technology dating back to 1963. The proposed membrane will enable the manufacture of highly efficient blood oxygenators with superior gas transfer, and reduced risk of deadly complications compared to currently used long term membranes.