Patent EA-000176-B1 (EA)
Title: Iron chelator as inhibitor of iron-mediated oxidation
Inventor: HORWITZ LAWRENCE
IPC: A61K31/55
Filed: 1996-01-26
Abstract: 1. A composition for protecting live tissue in a mammal from injury resulting from exposure to the hydroxyl free radical formed following reestablishment of fluid flow to a body organ after restriction of blood flow to that body organ comprising an effective amount of a desferriexochelin, and physiologically acceptable carrier characterized in that as desferriexochelin it contains an effective amount of at least one desferriexochelin of formula   wherein R1, is selected from the group consisting of (CH2)n COOCH3 and (CH2)xCH=CH(CH2)yCOOCH3 with n being from 1 to 7 and (x + y) being from 1 to 5 R2 is a chemical moiety substituted at any of the 4 open sites on the ring, said chemical moiety being selected from the group consisting of alkyl group, sulfonamide group, hydroxyl, halogen, acetyl, carbamyl, amino group and NO2 and combinations thereof; and R3 is selected from the group consisting of H and CH3, said desferriexochelins having a molecular weight of from about 716 to about 826 daltons. 2. The composition of Claim 1 wherein the live tissue is myocardium and the fluid is selected from the group consisting of reperfusion solution and cardioplesia solution. 3. The composition of Claim 1, said composition including a mixture of desferriexochelins having a molecular weight of 772 and 782 daltons. 4. The composition of Claim 1, said composition including a mixture of relatively nonpolar desferriexochelins characterized by n being a whole number from 5 to 7. 5. The composition of Claim 1, said composition including a mixture of relatively nonpolar desferriexochelins characterized by (x+y) being 4 or 5. 6. A composition for preventing injury to living tissue in a mammal from the presence of ion mediated, hydroxyl radical formation comprising an effective amount of at least one desferriexochelin and physiologically acceptable carrier characterized in that as desferriexochelin it contains an effective amount of at least one desferriexochelin of formula   wherein R1, is selected from the group consisting of (CH2)n COOCH3 and (CH2)xCH=CH(CH2)yCOOCH3 with n being from 1 to 7 and (x + y) being from 1 to 5 R2 is a chemical moiety substituted at any of the 4 open sites on the ring, said chemical moiety being selected from the group consisting of alkyl group, sulfonamide group, hydroxyl, halogen, acetyl, carbamyl, amino group and NO2 and combinations thereof; and R3 is selected from the group consisting of H and CH3, said desferriexochelins having a molecular weight of from about 716 to about 826 daltons. 7. Composition of formula   wherein R1 is a chemical moiety selected from the group consisting of (CH2)n CH3, (CH2)n COOH,, (CH2)n COO R, where R is an alkyl group and (CH2)n. CONH2; R2 is a chemical moiety substituted at any of the 4 open sites on the ring, said chemical moiety being selected from the group consisting of alkyl groups, sulfonamide group, hydroxyl, halogen, acetyl, carbamyl, amino group and NO2 and combinations thereof; R3 is a chemical moiety selected from the group consisting of side chains found on β-hydroxy amino acids which are capable of forming cyclic oxazoline structures; R4a, R4b, R5a, R5b are chemical moieties selected from the group consisting of H, alkyl groups or substituted alkyl groups, and *represents chiral centers which may be R or S. 8. The composition of Claim 7 wherein said compound is selected from the group consisting of saturated and unsaturated compounds, the saturated compounds having masses of 660, 674, 688, 702, 716, 730, 744, 758, 772, 786, 800. 814 and 828 daltons, the unsaturated compounds having masses of 686, 700, 714, 728, 742, 756, and 770 daltons. 9. The process of metal chelate forming of formula:   characterized in that said process includes the treatment of the composition by a solution, comprising ion metal M where M is selected from the group consisting of iron, lead, aluminum, cadmium, nickel, silver, gold, arsenic, magnesium, manganese, zinc, copper, rubidium, niobium, zirconium, tantalum, vanadium, gallium, platinum, chromium, scandium, yttrium, cobalt, titanium, sodium and potassium. 10. The metal chelate of formula   where M is selected from the group consisting of iron, lead, aluminum, cadmium, nickel, silver, gold, arsenic, magnesium, manganese, zinc, copper, rubidium, niobium, zirconium, tantalum, vanadium, gallium, platinum, chromium, scandium, yttrium, cobalt, titanium, sodium and potassium. 11. The metal chelate of Claim 10 wherein M is iron.