Necrosis and Ischemia
A separate potential application of carbohydrate chemistry is as an injectable antinecrosis drug, both for the prevention of necrosis and the treatment of ischemic conditions that may lead to necrosis. The drug consists of a stabilized glycoprotein composition contain oxygen-rechargeable iron, targeting both human and animal tissues and organ systems deprived of oxygen and in need of metabolic support.
Necrosis is 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 dementia, Lou Gehrig’s disease (ALS), septic shock, liver cirrhosis, chronic hepatitis, pancreatitis, diabetes, acute or critical limb ischemia, gangrene, chronic pressure ulcers, and many others. Necrosis occurs following ischemia (a 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.
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.
The new approach to treatment of ischemic tissue and prevention of necrosis is fundamentally different; it is a new chemical entity (NCE), not a biologic blood substitute, with a modified Heme chemical structure. The new compound prevents methemoglobin formation associated with the adverse effects of vasoconstriction and myocardial infarction. Furthermore, because of its extremely small molecular size—roughly 1/5,000th the size of a red blood cell—it is able to perfuse constricted, ischemic capillaries that 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.
One such complication is limb ischemia, a chronic condition of severe obstruction of the peripheral circulation that results in severe pain in the extremities; lower-limb ischemia is a life-threatening complication for patients with poorly controlled diabetes and affects 10 percent of the diabetic population. The new compound is a glycoprotein-derived substance that is sourced from a biological mixture, which is prone to immunologic activity, and the agent is purified by a novel processing technology. In general, the human body conserves the protein and recaptures amino acid moiety. The compound is broken down and eventually is collected in the spleen or liver, or it is simply eliminated by reversible endocytic processes in the kidneys.
A veterinary facsimile of this compound is also under development, due to an unmet need in this market for blood replacement and oxygen delivery to damaged or ischemic tissue due to trauma, surgery anemia, and other disease conditions. This can serve as an oxygen delivery mechanism for animals suffering ischemia or traumatic and surgical blood loss events.