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

• 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
• 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

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/项目主任(最后、第一、中间)：Patterson，Steven E. 项目摘要/摘要 在恐怖袭击中使用氰化物导致大规模伤亡的风险是真实的，氰化物包括在 化学威胁风险评估(CTRA)清单。作为回应，NIH反击指控发展 有效的医学对策，这个项目的重点是开发一种有效的药物/装置 将我们的速效解毒剂磺胺根联合应用于氰化物暴露的受害者。我们有 先前证明了我们实验室中发现的一种新的氰化物拮抗剂磺胺根(Patterson， 药物设计中心)在小鼠、猪和兔模型上有效地逆转致命的氰化物毒性 接触氰化物。我们对磺胺类药物疗效的论证包括剂量优化、药代动力学、 物种论证、配方优化和安全评估。为了进一步发展我们的事业 对策，WindGap Medical的自动注射器设计将被定制以适应Sulanegen的 给药特性。WindGap Medican-明尼苏达州财团的最终目标是1)获得 FDA的IND/IDE，2)进行临床试验，3)根据动物规则获得FDA的批准。这件事的重点是 因此，建议是关于开发优化的组合自动注射器/磺酸铅， 根据PAR-16-331，在非GLP研究中证明该铅的有效性和安全性，以及 为BARDA下的下一轮资金奠定基础，这将使IND能够进行研究。