# US 10,245,256 B2 · Nitroxides for use in treating or preventing diabetes and obesity

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- Number: US 10,245,256 B2
- Document ID: US10245256B2
- Status: Granted
- Kind: B2
- Application number: 15/382,398
- Filed: 2016-12-16
- Published: 2017-04-06
- Granted: 2019-04-02
- Earliest claimed: 2005-02-02
- Assignees: Mitos Pharmaceuticals, Inc.
- Applicants: Mitos Pharmaceuticals, Inc.
- Inventors: Louis Habash; Clarence Jones
- Web page: https://patentgrep.com/patent/US10245256B2

## CPC

- A61K 31/445: Non condensed piperidines, e.g. piperocaine
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 5/50: for increasing or potentiating the activity of insulin
- A61K 31/40: having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## 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).

## Claims

### Claim 1

A method of treatment comprising:
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, wherein the nitroxide antioxidant is selected from the following formulas:
wherein X is selected from O— and OH, and R is selected from COOH, CONH2, CN, and CH2NH2;
wherein X is selected from O— and OH, and R1 is CH3, R2 is C2H5, or R1 and R2 taken together are spirocyclohexyl;
wherein X is selected from O— and OH and R is selected from CONH2; and
wherein X is selected from O— and OH and R is selected from H, OH, and NH2, or wherein the nitroxide antioxidant is selected from the group consisting of 4-Oxo-2,2,6,6-tetramethylpiperidine-1-oxyl, 4-(2-bromoacetamido)-2,2,6,6-tetramethylpiperidine-1-oxyl, 4-(ethoxyfluorophosphonyloxy)-2,2,6,6-tetramethylpiperidine-1-oxyl, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl, 4-(2-iodoacetamido)-2,2,6,6-tetramethylpiperidine-1-oxyl, 4-isothiocyanato-2,2,6,6-tetramethylpiperidine-1-oxyl, 4-maleimido-2,2,6,6-tetramethylpiperidine-1-oxyl, 4-(4-nitrobenzoyloxyl)-2,2,6,6-tetramethylpiperidine-1-oxyl, and 4-phosphonooxy-2,2,6,6-tetramethylpiperidine-1-oxyl.

### Claim 2 (depends on 1)

The method of claim 1, wherein the subject has not been diagnosed with diabetes, or wherein the subject has silent diabetes.

### Claim 3 (depends on 1)

The method of claim 1, wherein the effective amount of the one or more nitroxide antioxidants is within a range of 0.01-300 mg/kg.

### Claim 4 (depends on 1)

The method of claim 1, wherein the effective amount of the one or more nitroxide antioxidants is within a range of 0.1-250 mg/kg.

### Claim 5 (depends on 1)

The method of claim 1, wherein the subject is predisposed or at risk for developing diabetes.

### Claim 6 (depends on 1)

The method of claim 1, wherein the subject has a family history of diabetes.

### Claim 7 (depends on 1)

The method of claim 1, wherein the subject has an eye disease.

### Claim 8 (depends on 1)

The method of claim 1, wherein the subject has a nephropathy.

### Claim 9 (depends on 1)

The method of claim 1, wherein the subject has a sensory or motor neuropathy.

### Claim 10 (depends on 1)

The method of claim 1, wherein the subject has a vascular disease.

### Claim 11 (depends on 1)

The method of claim 1, wherein the subject has a gastrointestinal dysfunction.

### Claim 12 (depends on 1)

The method of claim 1, wherein the subject has a genitourinary dysfunction.

### Claim 13 (depends on 1)

The method of claim 1, wherein the subject has a diabetic risk factor and the amount of nitroxide antioxidant is effective to reduce the diabetic risk factor.

### Claim 14 (depends on 1)

The method of claim 1, wherein the level of TNF-α expression is reduced.

### Claim 15 (depends on 1)

The method of claim 1, wherein the level of adiponectin expression is increased.