Nitroxides for use in treating or preventing diabetes and obesity
Inventors
Habash, Louis • Jones, Clarence
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10245256-B2
Publication Date
2019-04-02
Expiration Date
Abstract
Pharmaceutical compositions are provided that are useful in treating diabetes. The compositions comprise a pharmaceutically acceptable carrier, and an effective therapeutic or prophylactic amount of a nitroxide antioxidant that alters the expression of genes related to diabetes. Methods are also provided for the use of the pharmaceutical compositions in the treatment or prevention of diabetes. In a preferred embodiment, the nitroxide antioxidant is Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl).
Core Innovation
The invention discloses nitroxide antioxidant pharmaceutical compositions comprising a pharmaceutically acceptable carrier, wherein the nitroxide antioxidant is a selected nitroxide antioxidant structure including 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol) and other representative nitroxide structural formulae. The disclosed method involves preventing and treating diabetes by altering expression of diabetes-related genes in a subject.
The disclosed approach includes identifying a subject having elevated TNFα levels and administering an amount of a nitroxide antioxidant effective to reduce said levels in the subject. The text further relates intracellular levels of diabetes-related proteins to the administration of Tempol and reports increased cardiac expression of keratinocyte growth factor (KGF/FGF7) and increased adipose expression of adiponectin (ADIPOQ) after Tempol administration.
Claims Coverage
The provided independent claim is a method of treatment using a nitroxide antioxidant to reduce elevated TNFα levels, with one core inventive feature and dependent refinements directed to biomarker expression, subject context, and dose range.
Treating elevated TNFα by administering a nitroxide antioxidant
Identifying a subject having elevated TNFa levels, and administering to the subject an amount of a nitroxide antioxidant effective to reduce said levels in the subject.
Nitroxide antioxidant selected from specified formulas and listed 4,2,2,6,6-tetramethylpiperidine-1-oxyl derivatives
Selecting the nitroxide antioxidant from nitroxide antioxidant formulas wherein X is selected from O— and OH, R is selected from COOH, CONH2, CN, and CH2NH2; or R1 is CH3 and R2 is C2H5; or R1 and R2 taken together are spirocyclohexyl; and additionally selecting from the group consisting of 4-Oxo-2,2,6,6-tetramethylpiperidine-1-oxyl and multiple specified 4-substituted 2,2,6,6-tetramethylpiperidine-1-oxyl nitroxides including 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl.
Dose range for the effective amount of nitroxide antioxidant
Using an effective amount of one or more nitroxide antioxidants within a range of 0.01–300 mg/kg.
Reducing TNFα expression
Reducing the level of TNF-α expression.
Increasing adiponectin expression
Increasing the level of adiponectin expression.
Treating a subject with silent diabetes or not diagnosed with diabetes
Applying the method to a subject who has not been diagnosed with diabetes or has silent diabetes.
Treating a subject having vascular disease
Applying the method for a subject who has a vascular disease.
Across the independent claim and its dependent refinements, the core coverage is a nitroxide antioxidant method that targets elevated TNFα by administering a nitroxide antioxidant selected from specified structural formulas and listed derivatives, with further refinements including TNF-α expression, adiponectin expression, subject context, and an effective dose range in mg/kg.
Stated Advantages
Reduces elevated TNFa levels in the subject.
Reduces TNF-α expression.
Increases adiponectin expression.
Documented Applications
Preventing and treating diabetes by altering expression of diabetes-related genes using nitroxide antioxidant pharmaceutical compositions.
Interested in licensing this patent?