Tissue Oxygenation and Prevention of Necrosis
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 the outcome of severe and acute injury. It is involved in many pathological conditions such as, heart attack, brain injuries (TBI, CTE) and stroke, neurodegenerative diseases such as Alzheimer’s, dementia, Lou Gherig’s disease (ALS), 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 in a hyperbaric chamber. This pressurized oxidative environment is not without its risk. 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.
For decades, oxygen carriers have been developed for perfusion and oxygenation of ischemic tissue. None have succeeded through the FDA for human. These products were either blood-derived elements, synthetic perfluorocarbons or red blood cell modifiers. Several of the Hemoglobin-Based Oxygen Carriers (HBOC), contained nonfunctional impurities. These products failed to secure FDA approval. Our approach to treatment of ischemic tissue and prevention of necrosis is fundamentally different. Boston Therapeutics’ injectable investigative material, IPOXYN™ is a New Chemical Entity (NCE) and not considered a biologic blood substitute. IPOXYN™ is a modified heme chemical structure. Furthermore, because of IPOXYN™’s extremely small molecular size, roughly 1/5,000th the size of a red blood cell, it is able to perfuse constricted, ischemic capillaries which are inaccessible to red blood cells. This small molecular size has been proposed to be of particular significance in treating vascular complications of diabetes since red blood cells may already be enlarged and lower limb vasculature may be compromised.
We also intend to file a registration for an investigative material-like IPOXYN™ for veterinary applications under a proposed a proposed trade name OXYFEX™. We are unaware of any drug currently on the market for animals that can deliver oxygen, and there is only limited “blood banking” for animals despite a constant need. OXYFEX™ could serve as the only available oxygen delivery mechanism for animals suffering ischemic or traumatic and surgical blood loss events. We anticipate to commence in the marketing OXYFEX™, or a similar material, which we view as a potentially lucrative market in 2019. We anticipate that there are at least 15,000 small animal veterinary practices in the U.S., another 4,000 mixed animal practices treating small and large animals in the U.S. and approximately 22,000 small animal practices in Europe.
The FDA Center for Veterinary Medicine approved a bio-similar product to OXYFEX™ named Oxyglobin® in 1998 and the European Commission approved Oxyglobin® in 1999, in both cases for the treatment of canine anemia, regardless of the cause. Since Oxyglobin® is no longer available, we believe that the potential veterinary market for OXYFEX™ in the U.S., EU and Japan could exceed $250 million in sales annually within the five years after introduction due to the very large internet data base and opportunity of distribution. In addition, China as an emerging veterinary market with collateral market extensions such as The Shanghai Forum into Central Asian as well as BRICS Forum for the world’s most populous countries provide exciting market horizons for the product.