Novel Dense Hollow Fiber for Blood Gas Exchange

描述(申请人提供)：MedArray在SBIR一期和二期下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。因为ECMO可以持续1天以上，所以通常使用致密的膜而不是微孔膜来防止血浆泄漏。ECMO的首选膜是硅胶，因为它具有良好的血液相容性，而且没有血浆渗漏的孔。在美国，目前FDA批准用于长期应用的唯一氧合器是美敦力的ECMO氧合器。然而，这种螺旋缠绕的平板硅氧合器的设计可以追溯到1963年，它有许多缺点，包括血液停滞、最小对流混合、较大的血液接触表面积和高血流动力学阻力。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有效的基于中空纤维的长期氧合器。我们在第一阶段和第二阶段的研究表明，我们的硅酮中空纤维的性能优于螺旋缠绕硅胶膜，在气体传输和血小板趋势方面与微孔膜相当。然而，我们的硅胶膜不能像微孔膜那样泄漏血浆或大量栓塞气体进入血液侧。此外，我们已经在11天的体内研究中表明，我们的膜可以发挥并维持长期心肺支持的严酷。MedArray的硅胶膜中空纤维将使ECMO氧合器在美国和海外成为强大的市场竞争者。这项建议旨在继续开发我们的专利致密膜中空纤维，同时专注于与在临床氧合器中实施我们的膜相关的所有方面。具体地说，我们将按照FDA的指导方针调查膜材料对安全性、有效性和生物相容性的影响，以最终满足临床使用前的要求和期望。我们还将在长期的体内研究中严格测试我们的氧合器膜的气体传输性能和血栓形成能力。最后，我们将继续改进我们的膜制造工艺，通过评估与质量控制和成本降低相关的参数，最终建立一个符合良好制造规范(GMP)的健壮和受控工艺。这项研究和开发工作将产生一种用于长期血液气体传输的膜，可以取代可追溯到1963年的现有膜技术。与目前使用的长期膜相比，建议的膜将使高效血液氧合器的制造具有更好的气体传输能力，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.