SBIR Phase II: Scale-up Manufacturing of Nitric Oxide Nanotechnology for Healthcare Infections

这个小型企业创新研究(SBIR)第二阶段项目旨在开发必要的工艺和工程控制，以扩大一氧化氮释放活性药物成分(API)的生产。其中一个应用是治疗糖尿病足部溃疡的伤口愈合产品。该项目将侧重于1)优化将一氧化氮释放原料药的生产规模扩大到可重复的1公斤批次所需的工艺参数，以及2)实施分析方法，以满足研究新药(IND)申请的化学、制造和控制(CMC)部分的要求。预期的结果是一种能够生产大批量原料药的制造方法，这些原料药适合用于糖尿病足部溃疡的伤口愈合产品或其他一氧化氮释放药物的IND提交。该项目的更广泛/商业影响将是为糖尿病足部溃疡的治疗提供新的护理标准的潜力。目前，还没有一种产品可以同时解决糖尿病足溃疡的伤口愈合和感染问题。糖尿病足溃疡的感染问题尤其严重，原因是缺乏正常的皮肤屏障功能，伤口长期暴露于外部环境(数月至数年)，肢体血液循环不良，限制了炎症细胞向感染部位的迁移，以及最近对生物膜形成的了解，生物膜的形成可以保护细菌免受局部应用的抗菌剂和全身应用的抗生素的影响。一氧化氮释放的伤口愈合疗法有可能解决糖尿病足部溃疡的感染和愈合问题。

This Small Business Innovation Research (SBIR) Phase II project aims to develop the process and engineering controls necessary to scale up the manufacturing of a nitric-oxide-releasing active pharmaceutical ingredient (API). One of the applications is a wound-healing product for diabetic foot ulcers. This project will focus on 1) optimizing the process parameters required to scale production of a nitric-oxide-releasing API to reproducible 1 kg batches, and 2) implementing the analytical methodologies to meet the requirements of the Chemistry, Manufacturing and Control (CMC) sections of an Investigational New Drug (IND) application. The expected outcome is a manufacturing process capable of producing large batches of the API that are suitable for an IND submission of a wound-healing product for diabetic foot ulcers or other nitric-oxide-releasing drug. The broader/commercial impacts of this project will be the potential to provide a new standard of care for the treatment of diabetic foot ulcers. Currently, there are no products that address both wound healing and infection in diabetic foot ulcers. Infection is particularly problematic in diabetic foot ulcers due to the lack of normal skin barrier function, long duration of wound exposure to the external environment (months to years), poor blood circulation to the extremities that limits the migration of inflammatory cells to the site of infection, and the recent understanding of biofilm formation which protects bacteria from topically applied antimicrobials and systemically administered antibiotics. Nitric-oxide-releasing wound-healing therapeutics have the potential of addressing both infection and healing in diabetic foot ulcers.