SBIR Phase I: Manufacturing and Characterization of a Synthetic Platelet (SynthoPlateTM) Technology

SBIR 第一阶段：合成血小板 (SynthoPlateTM) 技术的制造和表征

• 批准号: 1745881
• 负责人: Michael Bruckman
• 金额: $ 22.5万
• 依托单位: Haima Therapeutics, LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-01 至 2019-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1745881&HistoricalAwards=false
• 关键词: SBIR; Phase; Manufacturing; Characterization; Synthetic

This SBIR Phase I project aims to further the development a novel nanoparticle-based synthetic platelet technology for the treatment of internal, non-compressible hemorrhage after traumatic injury. Trauma is the leading killer of people aged 1-46, and uncontrollable hemorrhage after injury is the cause of 35% of pre-hospital trauma deaths and 90% of military combat casualties. This is because there are currently no pre-hospital treatment options for internal, non-compressible hemorrhage. If the patient reaches a medical treatment facility in time, the current standard of care is transfusion with blood products, including platelets. However, natural platelet products suffer from shortage in supply (due to donor shortage), difficulty in portability, high risk of bacterial contamination, very short shelf life (3-5 days), requirement of blood typing and cross matching, and multiple biologic side effects (e.g. immune response). Therefore, there exists a significant clinical need for a synthetic platelet surrogate that can address the above limitations and can be administered at point-of-injury or during en route care to stop the bleeding earlier and potentially save lives. Beyond the potential clinical and commercial impact, the proposed research will also provide multi-disciplinary educational and research opportunities in major STEM areas at undergraduate level to create future scientists and engineers.A synthetic platelet technology has been developed that can simulate the hemostatic mechanisms and capabilities of natural platelets while allowing large-scale manufacturing, sterilization, long shelf-life and portability. The technology consists of a platelet-mimetic lipid-based nanoparticle, heteromultivalently surface-decorated with three types of small synthetic peptide ligands that render cooperative mechanisms of binding to von Willebrand Factor (vWF) and collagen (platelet-mimetic injury site-selective adhesion mechanisms) and binding to stimulated form of GPIIb-IIIa on active platelets (platelet-mimetic injury site-directed aggregation mechanism). This patented design is unique in that it is currently the only design that combines these adhesion and aggregation properties of natural platelets on a single synthetic platform. Preliminary studies have established the platelet-mimetic functional mechanisms in vitro as well as its significant hemostatic therapy capability in vivo in small (mouse) and large (pig) animal models of hemorrhage in both prophylactic and emergency administration frameworks. Building on these promising results, this project aims to conduct translationally-directed studies to address technical hurdles associated with manufacturing the synthetic platelets with batch-to-batch consistency and long shelf life (1 year) at a range of storage conditions (widely varying temperatures, altitudes, etc), which would be highly relevant in austere civilian and military applications.

该SBIR I期项目旨在进一步开发一种新型的基于纳米颗粒的合成血小板技术，用于治疗创伤性损伤后内部，不可压缩的出血。创伤是1-46岁的人的主要杀手，受伤后无法控制的出血是院前创伤前死亡的35％的原因，而军事作战人员伤亡的90％。这是因为目前尚无院前治疗方案的内部，不可压缩的出血。如果患者及时到达医疗机构，那么当前的护理标准是血液产品（包括血小板）的输血。然而，天然血小板产品的供应不足（由于供体短缺），可移植性难度，细菌污染的高风险，搁板寿命非常短（3-5天），血液键入和交叉匹配的需求以及多种生物学副作用（例如，免疫反应）。因此，存在对可以解决上述局限性的合成血小板替代物的巨大临床需求，并且可以在伤害点或在途中护理期间进行管理，以阻止早期出血并可能挽救生命。除了潜在的临床和商业影响外，拟议的研究还将在本科级别的主要STEM地区提供多学科的教育和研究机会，以创建未来的科学家和工程师。已经开发了一种合成的血小板技术，可以模拟自然血液的止血机制和能力，同时允许大规模制造，消毒，长期和端口。该技术由一种基于血小板脂质的纳米颗粒组成，具有三种类型的小型合成肽配体的异性表面分配，这些配体具有与von Willebrand因子（VWF）结合的合作机制（VWF）和胶原蛋白（血小板模拟的位点性受伤粘附机制）的刺激性GOMIAS IMIAS INSISIS IMIA，刺激性粘合剂的形式（血小板模拟损伤部位指导的聚集机制）。该专利设计的独特之处在于目前，它是唯一将天然血小板在单个合成平台上结合的粘合剂和聚集特性的设计。初步研究已经在体外建立了体外的血小板模拟功能机制及其在预防和紧急给药框架中的小（小鼠）和大（小鼠）和大型（猪）动物模型的体内的明显止血治疗能力。在这些令人鼓舞的结果的基础上，该项目旨在进行翻译指导的研究，以解决与制造具有批处理一致性的合成血小板相关的技术障碍，并在一系列的存储条件下（广泛变化的温度，高度等），这在Anusteriernile公民和军事应用中与之高度相关。