Novel outside-in dialyzer with long filter life and reduced anticoagulation therapies

新型由外向内透析器，过滤器寿命长，并减少抗凝治疗

基本信息

批准号：
10264173
负责人：
MOHAMED E LABIB
金额：
$ 100万
依托单位：
NOVAFLUX, INC.
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-15 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10264173
关键词：
3-Dimensional Acute Aftercare Air Animal Testing Animals Anticoagulants Anticoagulation Area Biological Sciences Blood Blood Cells Blood Platelets Blood coagulation Blood flow Brain Chemistry Chronic Citrates Clinical Coagulation Process Complex Costs and Benefits Country Data Dementia Deposition Development Dialysis patients Dialysis procedure Diffuse Embolism Engineering Equipment Excision FDA approved Fiber Filtration Frequencies Future Geometry Health Personnel Healthcare Hemodialysis Hemofiltration Hemorrhage Heparin Hour Housing In Vitro Industry Kidney Kidney Diseases Legal patent Life Liquid substance Lung Membrane Minor Modality Modeling Modification Organ Pathway interactions Patients Performance Phase Povidone Procedures Process Production Renal Replacement Therapy Research Risk Running Skin Surface System Technology Testing Thinness Thrombus Time Translating Treatment Cost base blood filter blood formation blood pressure regulation cost design hemocompatibility heparin-induced thrombocytopenia improved in vivo innovation ischemic lesion manufacturing process multidisciplinary new technology novel optimal treatments pressure prevent programs prototype scale up sheep model solute treatment duration wearable device

项目摘要

7. Project Summary/Abstract [Revised] For the past 60 years all hollow fiber dialyzers have had intraluminal blood flow. Novaflux outside-in filtration (OIF) creates a new design paradigm for hollow fiber dialyzers, changing dialyzer flow distribution so that blood flows on the outside of the fiber and dialysate flows in the intraluminal space. This development reduces the need for anticoagulation for acute or chronic dialytic therapies, including hemodialysis (HD) and provides increased filter life for continuous renal replacement therapies (CRRT). In vitro data using conventional dialyzers with OIF flow have found increased filter life to over 100 hours as compared to ~24 h with standard flow with statistically equivalent clearance. In OIF, thrombi have a minimal effect on the blood flow or filter pressure, diffusive clearance, or filtrate flux due to dynamic three-dimensional interconnected flow channels created in the inter fiber space. Novaflux research has developed prototype fibers that reverse the conventional dialyzer membrane structure to provide a thin tight smooth hemocompatible outer skin. The OI fiber will prevent damage to blood cells or formation of platelet aggregates. Novaflux OI filter housings optimize the blood inlet design using novel flow geometries, modeling and computation flow dynamics to provide steady blood velocity and uniform blood flow distribution. OIF dialyzers will be able to be produced by current dialyzer production equipment with relatively minor modifications. The value proposition of OI dialyzers is to reduce or eliminate the need for anticoagulation for chronic hemodialysis. This brings about key benefits including: 1) Lowering risk of heparin related complications such as bleeding and blood loss post treatment; 2) Providing a no-anticoagulation alternative for Heparin-Induced Thrombocytopenia; 3) Lowering the cost by $0.70 to $1.60 per treatment due to reduction in the use of heparin; 4) Reduction of microemboli which may pass from the extracorporeal circuit to the patient, causing ischemic lesions in organs such as the brain, which may contribute to dialysis dementia; and 5) Lower clotting potential facilitates development of wearable renal treatments. The OI filter can help acute dialytic renal treatments by providing no or reduced anticoagulation and longer filter life in CRRT, which translates into: 1) Lower cost and complexity for the healthcare provider; and 2) Reduced need for complex anticoagulation regimes, e.g., regional citrate anticoagulation. The Phase II will scale up the OIF membrane and housings to produce prototype OI dialyzers for in vitro and animal studies to characterize performance and hemocompatibility. These studies will quantify the potential of OI technology to eliminate or reduce anticoagulation for dialytic therapies and to provide clinical benefits and cost reductions compared to current acute and chronic therapies. The Specific Aims of this two year program are: Aim 1: Development of pilot scale production of OI fiber; Aim 2: Design the housing for the outside-in filter based on CFD analysis and develop the dialyzer manufacturing/construction process for limited production runs; Aim 3: To perform Ex vivo testing for the OI membrane and OI filter; and Aim 4: To perform in vivo animal testing in the sheep model. The OI technology will also enable the development of wearable technologies due to inherent benefits of longer filter life.

7. 项目总结/摘要[修订] 在过去的 60 年里，所有中空纤维透析器都具有腔内血流。 Novaflux 由外向内过滤 (OIF) 为中空纤维透析器创建了新的设计范例，改变了透析器的流量分布，使血液透析液在纤维外侧流动，透析液在管腔内流动。这一发展减少了急性或慢性透析治疗（包括血液透析 (HD)）需要抗凝，并提供延长连续肾脏替代疗法 (CRRT) 的过滤器寿命。使用常规的体外数据与标准的约 24 小时相比，采用 OIF 流量的透析器过滤器寿命延长至 100 小时以上流量具有统计上等效的间隙。在 OIF 中，血栓对血流或过滤器的影响很小由于动态三维互连流道而产生的压力、扩散间隙或滤液通量在纤维间空间中创建。 Novaflux 研究开发出原型纤维，可逆转传统透析膜结构提供薄而紧密、光滑的血液相容性外皮。 OI 纤维可防止血液受损细胞或血小板聚集体的形成。 Novaflux OI 过滤器外壳采用新颖的技术优化了血液入口设计流动几何形状、建模和计算流动动力学，以提供稳定的血流速度和均匀的血液流量分布。 OIF 透析器将能够通过现有的透析器生产设备进行生产相对较小的修改。 OI 透析器的价值主张是减少或消除慢性病患者抗凝的需要血液透析。这带来的主要好处包括： 1) 降低肝素相关并发症的风险，例如治疗后出血和失血； 2) 为肝素诱导的抗凝提供一种非抗凝替代方案血小板减少症； 3) 由于减少了使用，每次治疗的成本降低了 0.70 美元至 1.60 美元肝素; 4) 减少可能从体外回路传递至患者的微栓子，从而导致大脑等器官的缺血性病变，可能导致透析性痴呆； 5) 降低凝血水平潜力促进了可穿戴肾脏治疗的发展。 OI 过滤器可以通过不提供或减少抗凝作用来帮助急性透析肾脏治疗 CRRT 中的过滤器寿命更长，这意味着： 1) 医疗保健提供者的成本和复杂性更低；和 2) 减少对复杂抗凝方案（例如区域柠檬酸盐抗凝）的需求。第二阶段将扩大 OIF 膜和外壳的规模，以生产用于体内的原型 OI 透析器。体外和动物研究来表征性能和血液相容性。这些研究将量化 OI 技术消除或减少透析治疗抗凝作用并为临床提供治疗的潜力与目前的急性和慢性疗法相比，具有益处并降低成本。两者的具体目标年度计划为：目标 1：开发 OI 纤维的中试规模生产；目标 2：设计外壳基于 CFD 分析的由外向内过滤器，并开发有限的透析器制造/施工工艺生产运行；目标3：对OI膜和OI过滤器进行离体测试；目标 4：执行在绵羊模型中进行体内动物测试。 OI技术也将推动可穿戴设备的发展技术，因为具有更长的过滤器寿命的固有优势。