IPOXYN™, a universal oxygen carrier, is an injectable Rx for prevention of necrosis and treatment of ischemic conditions which may lead to necrosis. IPOXYN™ oxygen carriers are in pre-clinical stage of drug development.
Necrosis and Ischemia
Cell death can occur through two main mechanisms, apoptosis and necrosis. Apoptosis is a tightly regulated process in the body and many of the intracellular proteins and enzymes involved are well characterized. Necrosis has been viewed in the past as an accidental pathological mode of cell death. Recently, evidence has indicated that some forms of necrotic cell death could be related to intrinsic cellular mechanisms.
Necrosis is always the outcome of severe and acute injury. It is involved in many pathological conditions such as, heart attack, brain injuries and stroke, neurodegenerative diseases such as Alzheimer’s Disease, dementia and Lou Gherig’s Disease, septic shock, liver cirrhosis, chronic hepatitis, pancreatitis, muscle necrosis, diabetes mellitus, acute or critical limb ischemia, gangrene, chronic pressure ulcers and many others.
Necrosis occurs following ischemia (shortage of oxygen supply to the tissue due to restriction in blood supply). The only treatment available at present for necrosis is providing oxygen by a high pressure facility. Thus, there is a crucial need to develop drugs for prevention and treatment of this pathology.
Limb ischemia is a chronic condition of severe obstruction of the peripheral circulation that results in severe pain in the extremities. Due to the constriction of blood vessels, especially capillaries, red blood cells are unable to flow through them and this disruption in the microcirculation leads to the deprivation of oxygen, or ischemia. Complications include gangrenous sores and wounds that won’t heal, typically in the legs and feet. If left untreated, these lesions can result in amputation of the affected limb. Lower limb ischemia is a life-threatening complication for patients with poorly-controlled diabetes and affects 10% of the diabetic population. Brem Harold, Tomic-Canic Marjana (2007). "Cellular and Molecular basis of wound healing in diabetes". JCI 117 (5): 1219–1222. doi:10.1172/JCI32169. PMC 1857239. PMID 17476353. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1857239
For decades, oxygen carriers have been developed for perfusion and oxygenation of ischemic tissue None have yet succeeded. These products were either blood-derived elements, synthetic perfluorocarbons or red blood cell modifiers. Several of the Hemoglobin-Based Oxygen Carriers (HBOC), contained nonfunctional methemoglobin impurities. These products failed to secure FDA approval based upon either poor outcomes in clinical trials or poorly formulated product.
Our approach to treatment of ischemic tissue and prevention of necrosis is fundamentally different. Boston Therapeutics’ injectable drug, IPOXYN™ is a New Chemical Entity (NCE) and not a biologic blood substitute. IPOXYN™ is a modified Heme chemical structure. A significant improvement over HBOCs, IPOXYN™ prevents methemoglobin formation associated with the adverse effects of vasoconstriction and myocardial infarction. Furthermore, because of IPOXYN™’s extremely small molecular size, roughly 1/5,000th the size of a red blood cell, IPOXYN™ is able to perfuse constricted, ischemic capillaries which are inaccessible to red blood cells. This small molecular size has particular significance in treating vascular complications of diabetes since red blood cells may already be enlarged and lower limb vasculature may be compromised.