Compositions and methods utilizing hydroxamates to scavenge oxidant toxins
OwnerDeanna Jean Nelsoninventor
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Abstract
Macromolecule compositions using hydroxamate or oxime groups covalently coupled with biological cells and macromolecules, and in particular, with albumin and acellular hemoglobin, are provided. In particular embodiments, hydroxamate or oxime groups are covalently coupled with acellular hemoglobin and compounded to provide several formulations for a red cell substitute that will possess oxidant toxin-scavenging properties. The invention also provides a method of preventing and treating pathologies related to the actions of oxidant toxins or oxidative stress in a mammal. The method comprises administering to a mammal a therapeutically effective amount of a macromolecule composition comprising a macromolecule coupled with at least one hydroxamate or oxime group.
Claims31
A macromolecule composition comprising a macromolecule covalently coupled with at least one group having the formula
- —C(═Q)—NH—OH,
- where Q is O, NH, or S, a thiohydroxamate, amidoxime, urea, thiourea, isourea, isothiourea, carbamate, thiocarbamate, or guanidine moiety, thereby imparting oxidant-toxin scavenging capabilities to the composition.
A macromolecule composition comprising a macromolecule covalently coupled with at least one group having the formula
- —C(═Q)—NH—OH,
- where Q is O, NH, or S, a thiohydroxamate, amidoxime, urea, thiourea, isourea, isothiourea, carbamate, thiocarbamate, or guanidine moiety, thereby imparting oxidant-toxin scavenging capabilities to the composition, wherein the oxidant toxin is a hydroxyl radical (HO.).
A macromolecule composition comprising a macromolecule covalently coupled with at least one group having the formula
- —C(═Q)—NH—OH,
- where Q is O, NH, or S, a thiohydroxamate, amidoxime, urea, thiourea, isourea, isothiourea, carbamate, thiocarbamate, or guanidine moiety, thereby imparting oxidant-toxin scavenging capabilities to the composition, wherein the oxidant toxin is a peroxyl radical.
A macromolecule composition comprising a macromolecule covalently coupled with at least one group having the formula
- —C(═Q)—NH—OH,
- where Q is O, NH, or S, a thiohydroxamate, amidoxime, urea, thiourea, isourea, isothiourea, carbamate, thiocarbamate, or guanidine moiety, thereby imparting oxidant-toxin scavenging capabilities to the composition, wherein the oxidant toxin is peroxynitrite.
A macromolecule composition comprising a macromolecule covalently coupled with at least one group having the formula
- —C(═Q)—NH—OH,
- where Q is O, NH, or S, a thiohydroxamate, amidoxime, urea, thiourea, isourea, isothiourea, carbamate, thiocarbamate, or guanidine moiety, thereby imparting oxidant-toxin scavenging capabilities to the composition, wherein the oxidant toxin is ferryl hemoglobin.
A macromolecule composition comprising a macromolecule covalently coupled with at least one group having the formula
- —C(═Q)—NH—OH,
- where Q is O, NH, or S, a thiohydroxamate, amidoxime, urea, thiourea, isourea, isothiourea, carbamate, thiocarbamate, or guanidine moiety, thereby imparting oxidant-toxin scavenging capabilities to the composition, wherein the oxidant toxin is the superoxide radical-anion.
A macromolecule composition comprising a macromolecule covalently coupled with at least one having the formula
- —CH═NH—OH.
A red cell substitute comprising an acellular hemoglobin composition in a physiologically compatible solution, wherein said hemoglobin composition comprises an acellular hemoglobin stabilizingly and covalently coupled with at least one group having the formula
- —C(═Q)—NH—OH,
- wherein Q is O, NH, or S, a thiohydroxamate, amidoxime, urea, thiourea, isourea, isothiourea, carbamate, thiocarbamate, or guanidine moiety.
A red cell substitute comprising an acellular hemoglobin composition in a physiologically compatible solution, wherein said hemoglobin composition comprises an acellular hemoglobin stabilizingly and covalently coupled with at least one group having the formula
- —CH═NH—OH.
A method for the prevention or treatment of an oxidative stress-related pathology in a patient, comprising the step of administering to said patient a therapeutically effective amount of a macromolecule composition comprising a macromolecule covalently coupled with at least one group having the formula:
- —C(═Q)—NH—OH,
- where Q is O, NH, or S, a thiohydroxamate, amidoxime, urea, thiourea, isourea, isothiourea, carbamate, thiocarbamate, or guanidine moiety.
A method for the prevention or treatment of an oxidative stress-related pathology in a patient, comprising the step of administering to said patient a therapeutically effective amount of a macromolecule composition, wherein said macromolecule composition comprises a macromolecule covalently coupled with at least one oxime group.
Dependencies are inferred from the claim text.