Abuchowski Abraham
Prolong Pharmaceuticals, South Plainfield, NJ, USA.
Artif Organs. 2017 Apr;41(4):346-350. doi: 10.1111/aor.12934.
Historically, blood substitutes were under development that would provide oxygen carrying capacity as well as fluid replacement for both trauma and surgical indications. Their development was halted by the inability of the products to deliver therapeutic amounts of oxygen targeted to hypoxic tissue as well as from the inherent toxicity of the molecules. This led to the concept of an oxygen therapeutic that would be targeted for indications caused by anemia/ischemia/hypoxia but would not exhibit the toxicity that plagued earlier products. The complex pathophysiology of diseases such as sickle cell and hemorrhagic stroke not only has hypoxia as a pivotal event but also includes inflammation and vasoconstriction that perpetuate the oxygen deprivation. There is a need for an effective therapeutic that addresses the multiple events of inflammation and oxygen deprivation. SANGUINATE acts as a dual mode carbon monoxide (CO) and oxygen delivery therapeutic. SANGUINATE is designed not only to treat hypoxia but also to act on concurrent pathologies such as inflammation and reperfusion injury. This expands the potential therapeutic utility of SANGUINATE beyond anemia into indications such as early brain injury and delayed kidney graft function, where inflammation plays a pivotal pathological role as well as in indications such as sickle cell disease where the inflammation and hypoxia contribute to the development of comorbidities such as vaso-occlusive crisis. Clinical trials in multiple indications are underway.
从历史上看，曾有血液替代品处于研发中，这类产品旨在为创伤和手术适应症提供携氧能力以及补充液体。然而，由于产品无法向缺氧组织输送治疗剂量的氧气，且分子本身具有毒性，其研发工作被迫停止。这催生了一种氧疗药物的概念，该药物将针对由贫血/缺血/缺氧引起的适应症，但不会表现出困扰早期产品的毒性。镰状细胞病和出血性中风等疾病复杂的病理生理学不仅以缺氧为关键事件，还包括炎症和血管收缩，这些会使缺氧状况持续存在。因此，需要一种有效的治疗方法来应对炎症和缺氧等多种情况。SANGUINATE作为一种一氧化碳（CO）和氧气输送的双重模式治疗药物。SANGUINATE不仅旨在治疗缺氧，还对诸如炎症和再灌注损伤等并发病症起作用。这将SANGUINATE的潜在治疗用途从贫血扩展到了诸如早期脑损伤和移植肾延迟功能恢复等适应症，在这些病症中炎症起着关键的病理作用，同时也适用于镰状细胞病等适应症，在这些病症中炎症和缺氧会导致血管闭塞性危机等合并症的发生。针对多种适应症的临床试验正在进行中。
