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

• 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
• 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

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.项目摘要/摘要[修订版] 在过去的60年里，所有的中空纤维透析器都有管腔内血流。Novelux由外向内过滤 (OIF)为中空纤维透析器创造了一种新的设计范例，改变了透析器的流量分布， 在纤维的外部流动，而透析液在管腔内空间流动。这一发展减少了 需要抗凝治疗急性或慢性透析治疗，包括血液透析（HD），并提供 延长连续性肾脏替代治疗（CRRT）的滤器寿命。体外数据使用常规 OIF流透析器的过滤器寿命延长至100小时以上，而标准透析器的过滤器寿命约为24小时 具有统计学等效间隙的流量。在OIF中，血栓对血流或滤器的影响极小 由于动态三维互连流动通道而产生的压力、扩散间隙或滤液通量 在纤维间空间中形成。 Novelux研究公司已经开发出了一种原型纤维，它可以逆转传统的透析器膜 结构以提供薄的紧密光滑的血液相容性外皮。OI纤维可以防止血液损伤 细胞或血小板聚集体的形成。Novelix OI过滤器外壳采用新颖的 流动几何形状、建模和计算流动动力学，以提供稳定的血液速度和均匀的血液 流量分配OIF透析器将能够通过当前的透析器生产设备生产， 相对较小的修改。 OI透析器的价值主张是减少或消除慢性透析患者的抗凝需求。 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， 治疗后出血和失血; 2）为肝素诱导的 血小板减少症; 3）由于减少使用抗血小板药物，每次治疗的费用降低了0.70美元至1.60美元。 肝素; 4）减少可能从体外回路进入患者的微栓子， 脑等器官的缺血性病变，可能导致透析性痴呆;以及5）凝血功能降低 潜在的促进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来帮助急性透析肾脏治疗， CRRT中的滤器寿命更长，这意味着：1）医疗保健提供者的成本和复杂性更低;以及2） 减少对复杂抗凝方案的需求，例如，局部柠檬酸盐抗凝。 第二阶段将扩大OIF膜和外壳的规模，以生产原型OI透析器， 体外和动物研究，以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的抗凝作用并提供临床 与目前的急性和慢性治疗相比，两人的具体目标 目标1：开发OI纤维的中试规模生产;目标2：设计 基于CFD分析的由外向内过滤器，并开发有限的透析器制造/构造过程 生产运行;目标3：对OI膜和OI过滤器进行离体试验;目标4：进行 在绵羊模型中的体内动物试验。OI技术还将使可穿戴设备的发展成为可能。 过滤器寿命更长的固有优势使其成为技术优势。