Synthetic catalytic free radical scavengers useful as antioxidants for prevention and therapy of disease
AssigneeEukarion, Inc.
InventorsBernard Malfroy-Camine, Susan Robin Doctrow
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Abstract
The invention provides antioxidant salen-metal complexes, compositions of such antioxidant salen-metal complexes having superoxide activity, catalase activity, and/or peroxidase activity, compositions of salen-metal complexes in a form suitable for pharmaceutical administration to treat or prevent a disease associated with cell or tissue damage produced by free radicals such as superoxide, and cosmetic and free radical quenching formulations of salen metal compounds.
Claims25
A method for preventing, arresting, or treating a free radical-associated disease state by administering to a patient a therapeutically-effective dose of an antioxidant salen-metal complex pharmaceutical composition comprising an antioxidant salen metal complex of the formula:
- 15
- wherein M is selected from the group consisting of Mn, Co, Fe, V, Cr. and Ni;
- A is an anion;
- n is either 0, 1, or 2;
- X1, X2, X3 and X4 are independently selected from the group consisting of hydrogen, silyls, aryls, arylalkyls, primary alkyls, secondary alkyls, tertiary alkyls, alkoxys, aryloxys, aminos, quaternary amines, heteroatoms, and hydrogen;
- Y1, Y2, Y3, Y4, Y5, and Y6 are independently selected from the group consisting of hydrogen, halides, alkyls, aryls, arylalkyls, silyl groups, aminos, alkyls or aryls bearing heteroatoms, alkoxys, and halide;
- and
- R1, R2, R3 and R4 are independently selected from the group consisting of hydrogen, aryl, fatty acid esters, substituted alkoxyaryls, heteroatom-bearing aromatic groups, arylalkyls, primary alkyls, secondary alkyls, and tertiary alkyls.
A method for treating cardiac tissue necrosis resulting from cardiac ischemia or acute lung injury from sepsis or endotoxemia, neuronal damage resulting from anoxia, or iatrogenic free-radical neurotoxicity toxicity resulting from MPTP intoxication, comprising administering a therapeutically effective dose of an antioxidant salen-metal complex selected from the group consisting of:
- C1, C4, C6, C7, C9, C15, C17, C20, C22, C23, C25, C27, C28, C31, C32, C33, C34, C35, C36, C37, C38, C39, C40, C41, C42, C43, C44, C45, C46, C47, C48, C49, C50, C51, and C52.
A method for treating ischemia/reoxygenation injury, comprising administering to a patient a therapeutically-effective dose of an antioxidant salen-metal complex pharmaceutical composition comprising an antioxidant salen metal complex of the formula:
- 16
- wherein M is selected from the group consisting of Mn, Co, Fe, V, Cr, and Ni;
- A is an anion;
- n is either 0, 1, or 2;
- X1, X2, X3 and X4 are independently selected from the group consisting of hydrogen, silyls, aryls, arylalkyls, primary alkyls, secondary alkyls, tertiary alkyls, alkoxys, aryloxys, aminos, quaternary amines, heteroatoms, and hydrogen;
- Y1, Y2, Y3, Y4, Y5, and Y6 are independently selected from the group consisting of hydrogen, halides, alkyls, aryls, arylalkyls, silyl groups, aminos, alkoxys, alkyls or aryls bearing heteroatoms, and halide;
- and
- R1, R2, R3 and R4 are independently selected from the group consisting of hydrogen, aryl, fatty acid esters, substituted alkoxyaryls, heteroatom-bearing aromatic groups, arylalkyls, primary alkyls, secondary alkyls, and tertiary alkyls.
A pharmaceutically acceptable composition comprising an antioxidant salen-metal compound having the structural formula selected from the group of compounds consisting of:
- C31, C32, C33, C34, C35, C36, C37, C38, C39, C40, C41, C42, C43, C44, C45, C46, C47, C48, C49, C50, C51, and C52.
A salen-metal complex having the structural formula selected from the group of compounds consisting of:
- C31, C32, C33, C34, C35, C36, C37, C38, C39, C40, C41, C42, C43, C44, C45, C46, C47, C48, C49, C50, C51, and C52.
A composition comprising a predetermined amount of a salen-metal complex selected from the group of compounds consisting of:
- C31, C32, C33, C34, C35, C36, C37, C38, C39, C40, C41, C42, C43, C44, C45, C46, C47, C48, C49, C50, C51, and C52, wherein said preselected amount comprises a predetermined level of superoxide dismutase activity and/or catalase activity per mmole dissolved in an aqueous solution.
Dependencies are inferred from the claim text.