Optimization of a Combined Drug and Delivery Device for Treatment of Cyanide Poisoning

氰化物中毒治疗联合给药装置的优化

基本信息

批准号：
10474983
负责人：
STEVEN E PATTERSON
金额：
$ 66.29万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-15 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10474983
关键词：
Accidents Acute Address Animal Model Antidotes Award Ballistics Biological Models Characteristics Charge Chemicals Conduct Clinical Trials Custom Cyanides Development Devices Dose Drug Combinations Drug Delivery Systems Drug Design Drug Kinetics Evaluation Exposure to Family suidae Formulation Funding Gel Genetic Polymorphism Goals Histopathology Human Injections Intellectual Property Intervention Lead Legal patent Licensure Liquid substance Lysine Magnetic Resonance Imaging Medical Methods Military Personnel Minnesota Modeling Mus Oryctolagus cuniculus Particle Size Pharmaceutical Preparations Pharmacology Pilot Projects Poisoning Powder dose form Principal Investigator Property Rights Protocols documentation Research Personnel Risk Risk Assessment Safety Secure Security Site Source System Terrorism Therapeutic Therapeutic Uses Tissues Toxic effect United States National Institutes of Health Work analytical method animal rule antagonist aqueous chemical threat clinical translation commercialization design drug development drug discovery efficacy study in vivo mass casualty medical countermeasure method development mortality novel programs prototype response safety assessment

项目摘要

Principal Investigator/Program Director (Last, First, Middle): Patterson, Steven E. Project Summary/Abstract The risk of cyanide use in a terrorist attack resulting in a mass casualties is genuine and cyanide is included on the Chemical Threat Risk Assessment (CTRA) list. In response the NIH CounterACT charge to develop effective medical countermeasures, this project is focused on development of an effective drug/device combination to deliver our rapidly acting antidote, sulfanegen, to victims of cyanide exposure. We have previously demonstrated that sulfanegen, a novel cyanide antagonist discovered in our labs, (Patterson, Center for Drug Design) is effective in reversing lethal cyanide toxicity in murine, swine and rabbit models of cyanide exposure. Our demonstration of sulfanegen’s efficacy includes dose optimization, pharmacokinetics, species justification, formulation optimization, and safety assessment. In order to furthere develop our countermeasure, Windgap Medical’s autoinjector design will be customized to accommodate sulfanegen’s dosing characteristics. The Windgap Medican-Minnesota consortium’s ultimate goals are to 1) obtain an IND/IDE from the FDA, 2) conduct clinical trials and 3) FDA approval under the animal rule. The focus of this proposal is therefore on development of an optimized combined autoinjector/sulfanegen lead, demonstration of this lead’s efficacy and safety in non-GLP studies according to PAR-16-331, and establish the basis for a later round of funding under BARDA that will allow IND enabling studies.

首席研究员/项目总监（最后、第一、中间）：Patterson, Steven E. 项目概要/摘要在恐怖袭击中使用氰化物造成大规模人员伤亡的风险是真实存在的，并且氰化物已包含在恐怖袭击中化学威胁风险评估 (CTRA) 清单是为了响应 NIH CounterACT 的要求而制定的。有效的医疗对策，该项目的重点是开发有效的药物/设备组合，为氰化物暴露的受害者提供我们的速效解毒剂 sulfanegen。先前证明了我们实验室发现的一种新型氰化物拮抗剂 sulfanegen（Patterson，药物设计中心）可有效逆转鼠、猪和兔模型中致命的氰化物毒性我们对 sulfanegen 功效的论证包括剂量优化、药代动力学、物种合理性、配方优化和安全性评估，以进一步发展我们的产品。对策，Windgap Medical 的自动注射器设计将进行定制，以适应 sulfanegen 的要求 Windgap Medican-明尼苏达联盟的最终目标是 1) 获得 FDA 的 IND/IDE，2）进行临床试验，3）根据动物规则获得 FDA 批准。因此，建议结合开发优化的自动注射器/sulfanegen 引线，根据 PAR-16-331 在非 GLP 研究中证明该先导药物的有效性和安全性，以及为 BARDA 下一轮资助奠定基础，以支持 IND 的研究。