Hemorrhage is the leading cause of death from combat trauma and the second leading cause of civilian death. Trauma is mainly treated with intravenous liquids, such as isotonic crystalloid solutions. Although volume expansion is desirable, none of these solutions is capable of overcoming tissue oxygen deficits (ischemia). Proper use of transfused blood can assist in resuscitation;however there are significant problems with its use, including storage restraints, availability, typing, risk of disease transmission and immune suppression. These issues make the routine use of stored human blood for use outside the hospital impractical. In an attempt to overcome many of these issues, efforts have been made to develop hemoglobin based oxygen carrier (HBOCs) blood substitutes which have advantages such as decreased chance of disease transmission, lack of a need for typing, and most importantly improved availability with decreased storage demands. Prolong Pharmaceuticals has developed a unique HBOC product for the treatment of severe hemorrhagic shock consisting of a combination of PEGylated bovine hemoglobin (PEG-Hb) and hypertonic saline (HS). It is specifically designed to increase the oxygen carrying capacity of blood as well as to enhance the delivery of oxygen to tissues by keeping the vasculature open through its hypertonic-oncotic actions. We have found this product to be capable of rapidly restoring tissue oxygenation and repaying oxygen debt in an animal model of severe traumatic shock. In this Fast- Track SBIR grant, we will conduct the preclinical studies needed to support an IND to conduct clinical testing of the product. In the phase I component, we will conduct pharmacokinetic analysis of PEG-Hb/HS to define optimal dosing for follow up efficacy and toxicology assessment and to establish dosing parameters for future clinical studies. In the phase II SBIR component we will conduct additional efficacy studies to determine the extent of survival that PEG-Hb/HS induces in our animal model of trauma and will also perform toxicology assessment to support the future use of this product in the treatment of trauma.
The studies proposed in this grant are designed to further the development of PEG- Hb/HS as a hemoglobin based oxygen carrier to treat traumatic shock. We have shown that this product can reverse oxygen debt in an animal model of severe hemorrhagic shock and studies proposed in this grant will move forward the preclinical development of this product including additional efficacy studies and IND supporting pharmacokinetic and toxicology studies.
