Rapid Reconstitution of a Lyophilized, Bio-inspired, Artificial Red Blood Cell

冻干仿生人造红细胞的快速重建

基本信息

批准号：
10010242
负责人：
Esma Alp
金额：
$ 37.32万
依托单位：
KALOCYTE, 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：
2020-05-01 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10010242
关键词：
Address Adverse effects Affinity Albumins American Authorization documentation Benign Blood Blood Pressure Blood Substitutes Caring Cell physiology Characteristics Clinical Trials Design Collaborations Colloids Complex Country Department of Defense Development Environment Erythrocytes Event Freeze Drying Funding Goals Grant Hemoglobin Hemorrhage Hemorrhagic Shock Home environment Hospitals Human Immune response Individual Industry Intellectual Property Lactated Ringer&apos s Solution Life Liquid substance Lung Nitric Oxide Normal saline Osmolalities Osmolar Concentration Oxygen Patients Phase Physiological Plasma Plasmalyte A Pre-hospitalization care Process Production Publishing Red Cross Research Resources Resuscitation Risk Secure Small Business Innovation Research Grant Solid Sterility Testing Therapeutic Time Tissues Training Transfusion Translating Trauma Vascular blood supply Water Whole Blood base blood product cost effective crystalloid design expectation experience human study in vivo innovation mass casualty nanoencapsulated operation preclinical development pressure prevent preventable death prototype rapid technique reconstitution transfusion medicine vasoconstriction

项目摘要

PROJECT SUMMARY There is need for an artificial oxygen (O2) carrier to substitute for stored blood products, which at times are unavailable (pre-hospital care, austere environments, resource-limited countries), undesirable (risk of immune response), or in short supply to meet demand (mass casualty event). Moreover, transfusion of a crystalloid or colloid solution alone will lead to dilutional deficiencies of blood components such as red blood cells (RBCs), which are critical for delivering oxygen (O2) to the various tissues. KaloCyte's focus is to develop ErythroMer (EM), a lyophilized, bio-inspired, artificial RBC, which will transform how patients who need a transfusion are treated when stored RBCs or whole blood are not an option. Previous oxygen carrier products have had two major design flaws preventing them from mimicking RBC physiology: (1) inability to appropriately release O2 to tissues after capture in the lungs and (2) sequestration of nitric oxide (NO) resulting in vasoconstriction. EM is designed to not only carry O2 but also surmount the barriers encountered by prior oxygen carriers (intended as red blood cell substitutes). EM accomplishes this by emulating physiologic RBC O2 capture and delivery along with benign interaction with the vasculature. These key bio-inspired design features differentiate EM from previous attempts. Moreover, EM is designed for sterile lyophilization and so, is amenable to facile, rapid reconstitution after extended dry storage under ambient conditions. EM offers a pragmatic approach to a complex need and is designed for cost-effective production at scale. Our prototype has passed rigorous initial ex vivo and in vivo “proof of concept” testing. KaloCyte was founded so that we may translate EM innovations into a pragmatic therapeutic and as well as realize the commercial potential of a disruptive introduction into transfusion medicine. Our project goals are to enable rapid, facile reconstitution and establish the optimal colloid (albumin and freeze-dried plasma), and crystalloid (normal saline, lactated ringers, PlasmaLyte A) ratios for EM resuspension, while not disrupting the osmolality and oncotic pressure of blood. EM intellectual property is robust and secured by KaloCyte, which is supported by a solid research team, our CEO with a strong therapeutic industry background and scientific advisors, with experience in hemoglobin-based oxygen carrier development, lyophilization, transfusion medicine, hemorrhage & resuscitation, pre-clinical development and trial design. SBIR funding will enable KaloCyte to critical pre-clinical development in EM production and initiate groundwork required for IND authorization. Of note, our initial studies and the approach herein meet published FDA expectations for blood substitutes. Given the significant need and market potential we have hemorrhagic shock as the first indication for FDA approval. Following a successful trial for hemorrhagic shock, we would expand EM into other settings and exploit the design to extend efficacies beyond that of stored blood.

项目概要需要人工氧 (O2) 载体来替代储存的血液制品，而储存的血液制品有时会无法获得（院前护理、严峻的环境、资源有限的国家）、不可取（免疫风险）响应），或供应不足以满足需求（大规模伤亡事件）此外，输注晶体或单独的胶体溶液会导致红细胞（RBC）等血液成分稀释不足，对于向各种组织输送氧气 (O2) 至关重要，KaloCyte 的重点是开发 ErythroMer。 (EM)，一种冻干的仿生人工红细胞，它将改变需要输血的患者的治疗方式当无法选择储存红细胞或全血时进行治疗以前的氧载体产品有两种。阻止它们模仿红细胞生理学的主要设计缺陷：(1) 无法适当释放 O2 肺部捕获后的组织和（2）一氧化氮（NO）的隔离导致血管收缩。设计不仅可以携带氧气，还可以克服先前氧气载体遇到的障碍（旨在作为红细胞替代品）通过模拟生理红细胞 O2 捕获和输送来实现这一点。这些关键的仿生设计特征使 EM 与脉管系统产生良性相互作用。此外，EM 是为无菌冻干而设计的，因此可以方便、快速地进行。环境条件下长期干燥储存后的重构为复杂的情况提供了一种实用的方法。我们的原型是为大规模生产而设计的，并且已经通过了严格的初步体外和测试。 KaloCyte 的成立是为了让我们可以将 EM 创新转化为体内“概念验证”测试。务实的治疗，并实现颠覆性输血的商业潜力我们的项目目标是实现快速、简便的重构并建立最佳的胶体（白蛋白）。和冻干血浆）和晶体（生理盐水、乳酸林格氏液、PlasmaLyte A）比例用于 EM 重悬，同时不破坏血液的渗透压和渗透压，EM 知识产权是强大的。并由 KaloCyte 担保，KaloCyte 得到了坚实的研究团队的支持，我们的首席执行官拥有强大的治疗能力行业背景和科学顾问，具有血红蛋白氧载体开发经验，冻干、输血医学、出血和复苏、临床前开发和试验设计。资金将使 KaloCyte 能够进行 EM 生产的关键临床前开发并启动基础工作值得注意的是，我们的初步研究和本文的方法符合 FDA 公布的要求。鉴于对血液替代品的巨大需求和市场潜力，我们有失血性休克。作为 FDA 批准的第一个适应症，在成功进行失血性休克试验后，我们将扩大 EM 的范围。进入其他环境并利用该设计将功效扩展到储存血液之外。