SBIR-STTR Award

Clinical Challenge: In acute trauma, in the civilian setting, hemorrhage is the second most leading cause of death.1 In the military setting, 90% of potentially preventable deaths are caused by hemorrhage due to trauma.2,3 56% of civilian and 87% of military mortality caused by traumatic hemorrhage occurs pre-hospitalization. Adverse outcome in trauma patients during prehospital resuscitation is due to the unavailability of blood transfusions in the field leading to insufficient oxygenation. Traumatic brain injury (TBI) is the leading cause of disability in both civilians and military.4 Specifically, in the pre-hospital setting, hypoxia in TBI may be the most important secondary injury affecting mortality.5,6 A therapy that can be deployed rapidly, and safely en route to the hospital in the civilian and the battlefield settings could greatly reduce the trauma mortality rates due to both hemorrhage and TBI. We are developing an oxygen therapeutic, dodecafluoropentane emulsion (DDFPe), which has the potential to be administered in the prehospital setting. This could greatly prolong the time window for administration of follow-on therapies to trauma patients, thus increasing the likelihood of successful recovery. All fluorocarbon emulsions undergo a gradual increase in particle size due to Ostwald ripening.7 DDFPe has a two-year shelf-life at 4°C, about one year at room temperature and shorter shelf-life at higher temperatures due to particle size increase beyond specifications. We have discovered a means of maintaining the particle size of DDFPe within specification that affords at least a two-year shelf life even under potentially extreme conditions. Availability of an oxygen therapeutic in field conditions would allow it to be used in emergent settings maintaining vital oxygenation in civilian and military trauma. Overarching Hypotheses: Sonication of pre-filled syringes of DDFPe can be employed to produce in spec nanoemulsion suitable for IV administration. Ultimately, battery powered, portable, easy to use pre-filled syringe/sonication systems can be developed for field based applications. Specific Aims: 1. Demonstration of optimal acoustic parameters. 2. Demonstration that product composition is not affected by sonication. Expected Outcome: Successful completion of the study will determine the optimal ultrasound parameters to enable design of a portable, battery powered syringe/sonication device in Phase II of this development program.

Public Health Relevance Statement:
A therapy that can be deployed rapidly, and safely en route to the hospital for civilians and also for soldiers on the battlefield could greatly reduce the trauma mortality rates due to both hemorrhage and traumatic brain injury. Sonication of pre-filled syringes of dodecafluoropentane emulsion (DDFPe), an oxygen therapeutic, can be employed to produce in spec nanoemulsion suitable for IV administration. Ultimately, a battery powered, portable, easy to use, pre-filled syringe/sonication system can be developed for DDFPe administration in the pre-hospital setting.

Project Terms:
Acoustics; Acute; adverse outcome; Affect; base; Blood Transfusion; Brain; Brain hemorrhage; Caliber; Cause of Death; Cerebrovascular system; Clinical; Clinical Trials; Contrast Media; Data; design; Development; Devices; disability; Dose; Early Intervention; Emulsions; Excipients; experimental study; Family suidae; Fluorocarbon Emulsions; Frequencies; Glioblastoma; Hemorrhage; High temperature of physical object; Hospitals; Hour; Hypoxia; Injury; Ischemic Stroke; Legal patent; Life; meetings; Military Personnel; Modeling; mortality; nanoemulsion; neuroprotection; Outcome; Outcomes Research; Oxygen; particle; Particle Size; Patients; perfluoropentane; Pharmaceutical Preparations; Phase; Physiologic pulse; portability; Pre-hospital setting; pressure; Program Development; Property; Rattus; Recovery; Research; Resuscitation; Route; Sickle Cell Anemia; Soldier; Sonication; stroke; Syringes; System; Temperature; Testing; Therapeutic; Time; Trauma; Trauma patient; Traumatic Brain Injury; Traumatic Hemorrhage; Ultrasonography