Development of BIO 300 as a MCM for lethal radiation pneumonitis/fibrosis

项目摘要 迫切需要有效的医学对策来治疗放射性肺炎和 与急性辐射暴露的延迟效应相关的肺纤维化。伟大的 重要的是可以在没有医疗监督的情况下分发使用的对策，使 口服力强的对策具有较高的趣味性和重要性。为了解决这一未得到满足的需求， 人文公司正在开发BIO 300口服混悬剂(活性成分染料木素)以治疗 急性辐射暴露(DEARE)在肺部的延迟效应。金雀异黄素，一种非特异性酪氨酸 激酶抑制剂，有很强的安全性历史，并具有实质性的辐射防护作用，与其相关 具有较强的抗氧化能力、抗炎性能及其对细胞周期分裂的影响。在……里面 在这项提案中总结的临床前研究表明，bio300已经显著改善了 全胸肺移植后存活、减轻肺组织损伤和改善肺功能 辐射。这项建议的目的是确定BIO 300的最佳治疗剂量方案。 减少急性辐射对肺的损伤并最大限度地提高存活的可能性 胸部。放射性肺损伤的剂量反应和时间过程模型 损害的定义很好，将在拟议的研究中使用。还建议进行研究，以进一步 了解全身或局部照射对BIO300‘S药代动力学特性的影响。 拟议研究的总体目标是推动BIO 300作为一种医疗手段的发展 FDA批准的对策。拟议的工作建立在以下研发经验的基础上 人文公司将BIO 300作为急性呼吸道感染的医学对策 辐射暴露。未来发展的重点将是推动BION300的发展 进入大型动物药效试验，以确定在啮齿动物模型中观察到的阳性药效数据 转化为更大的动物。BIO300的持续发展无疑将扩大科学 知识库，并支持持续评价和开发代理，以预防和/或 治疗辐射暴露的急性和慢性影响。此外，随着BIO300的领先，S 作为一种医学放射对策，以及作为癌症放射治疗的辅助手段，它的发展 提供了通过关键的疗效试验加速开发过程的机会，并 执照。

Project Summary A significant need exists for effective medical countermeasures for radiation-induced pneumonitis and pulmonary fibrosis associated with the delayed effects of acute radiation exposure. Of great importance are countermeasures that can be distributed for use without medical supervision, making orally effective countermeasures of high interest and importance. To address this unmet need, Humanetics Corporation is developing BIO 300 Oral Suspension (active ingredient genistein) to treat the delayed effects of acute radiation exposure (DEARE) in the lung. Genistein, a non-specific tyrosine kinase inhibitor, has a strong history of safety, and has substantial radioprotective effects linked to its strong antioxidant capacity, anti-inflammatory properties, and its effects on cell cycle division. In preclinical studies summarized in this proposal BIO 300 has been shown to significantly improve survival, mitigate lung tissue injury, and improve pulmonary function following whole thoracic lung irradiation. The aim of this proposal is to determine the optimum therapeutic dosing regimen of BIO 300 to reduce lung damage and maximize the likelihood for survival following acute radiation exposure to the thoracic region. Models in which the dose response and timecourse of radiation induced pulmonary damage are well defined will be used in the proposed studies. Studies are also proposed to further understand the effect that total or partial body irradiation has on BIO 300’s pharmacokinetic properties. The overall goal of the proposed studies is to advance the development of BIO 300 as a medical countermeasure towards FDA approval. The proposed work builds on the R&D experience of Humanetics Corporation toward the development of BIO 300 as a medical countermeasure for acute radiation exposure. The main emphasis of future development will be to move BIO 300 development into large animal efficacy testing to determine if the positive efficacy data observed in the rodent model translates to a larger animal. Continued development of BIO 300 will undoubtedly expand the scientific knowledge base and support the continued evaluation and development of agents to prevent and/or treat the acute and chronic effects of radiation exposure. Moreover, with BIO 300’s advanced development as a medical radiation countermeasure, and as an adjunct to cancer radiotherapy, it presents an opportunity for an accelerated development course through pivotal efficacy trials and to licensure.