| 摘要 |
USE OF DISULFIRAM TO PROTECT CELLS AGAINST HYPOXIC OR ISCHEMIC DAMAGE This invention discloses a method of reducing hypoxic or ischemic damage to cells or organs, by administering a therapeutically effective quantity of disulfiram or a suitable salt or analog thereof. Previously, disulfiram has been used as alcohol-aversion therapy for alcoholics, and has been shown to be very safe and well-tolerated. This invention also discloses that it can be used as a cytoprotetive agent. When administered during or immediately after a hypoxic/ischemic crisis (such as a stroke, heart attack, cardiac arrest, asphyxiation, hemorrhage, or trauma involving blood loss) or before a patient is subjected to cardiac arrest or bypass during surgery, disulfiram can suppress damage by oxygenated free radicals, it can chelate copper and iron which would otherwise promote lipid peroxidation of cell membranes, and it can generate metabolites such as tryptophol that can suppress metabolic activity and demands in neurons and affected tissue. This invention also discloses rapid-release injectable formulations comprising disulfiram mixed with water, an organic compound having a plurality of hydroxyl groups (such as propylene glycol, dextrans, an cyclodextrins), and a buffer. Unlike slow-release injectable formulations designed to ensure that chronic alcoholics have significant quantities of disulfiram in their blood over prolonged periods of time, rapid-release injectable formulations are designed to reduce hypoxic or ischemic damage caused by crisis events.
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