# US 11,304,971 B2 · Metformin compositions and methods for treatment of diabetes

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- Number: US 11,304,971 B2
- Document ID: US11304971B2
- Status: Granted
- Kind: B2
- Application number: 16/264,595
- Filed: 2019-01-31
- Published: 2019-08-01
- Granted: 2022-04-19
- Earliest claimed: 2018-01-31
- Assignees: William H. Cross, III
- Applicants: William H. Cross, III
- Inventors: William H. Cross, III
- Web page: https://patentgrep.com/patent/US11304971B2

## CPC

- A61K 31/714: Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
- A61K 31/155: Amidines ([IMAGE cpc-sch-A61K-1029.gif]), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
- A61K 31/185: Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids (hydroxamic acids A61K31/16; peroxy acids A61K31/327)
- A61K 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00)
- A61K 31/4045: Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- 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

The invention provides compositions and methods to treat diabetes with improved formulations in which metformin is combined with at least three antioxidants that contain a stabilizing heteroatom adjacent to a saturated carbon and which help maintain a balance between antioxidant and pro-oxidant properties. The antioxidants include at least the combination of taurine, citrulline and methylcobalamin, and optionally include melatonin. The composition provides management of blood glucose levels comparable to metformin in the same dose without antioxidants, without the phenomenon of undermining metformin performance that is commonly observed in the presence of co-administered antioxidants.

## Claims

### Claim 1

A composition for treatment of diabetes comprising a pharmaceutically effective amount of metformin and
(a) taurine in an amount from 50 mg to 200 mg;
(b) citrulline in an amount from 25 mg to 100 mg;
(c) methylcobalamin in an amount from 40 μg to 440 μg; and
(d) beta-alanine in an amount from 10 mg to 90 mg.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the composition further comprises melatonin.

### Claim 3 (depends on 1)

The composition of claim 1 wherein the composition comprises metformin in an amount from 500 mg to 2,500 mg.

### Claim 4 (depends on 1)

The composition of claim 1 wherein the composition comprises metformin in an amount from 500 mg to 2,500 mg;
melatonin in an amount from 1 to 50 mg.

### Claim 5 (depends on 1)

The composition of claim 1 wherein the composition comprises:
a) metformin in an amount of 1,500 mg;
b) taurine in an amount of 125 mg;
c) citrulline in an amount of 60 mg; and
d) methylcobalamin in an amount of 240 μg.

### Claim 6 (depends on 1)

The composition of claim 1 wherein the composition comprises:
a) metformin in an amount of 1,500 mg;
b) taurine in an amount of 125 mg;
c) citrulline in an amount of 60 mg;
d) methylcobalamin in an amount of 240 μg; and
e) melatonin in an amount of 25 mg.

### Claim 7 (depends on 1)

The composition of claim 1 wherein the amount of taurine is selected from a range that is from 8% to 12% of the amount of metformin by weight.

### Claim 8 (depends on 1)

The composition of claim 1 wherein the amount of citrulline is selected from a range that is from 3% to 7% of the amount of metformin by weight.

### Claim 9 (depends on 1)

The composition of claim 1 wherein the amount of taurine is selected from a range that is from 150% to 250% of the amount of citrulline by weight.

### Claim 10 (depends on 1)

A method for treatment of diabetes comprising administering to a diabetic patient having the composition of claim 1.

### Claim 11 (depends on 10)

The method of claim 10, wherein the composition further comprises melatonin.

### Claim 12 (depends on 10)

The method of claim 10 wherein the composition comprises metformin in an amount from 500 to 2,500 mg.

### Claim 13 (depends on 10)

The method of claim 10 wherein the composition comprises metformin in an amount selected from the range of 500 to 2,500 mg;
melatonin in an amount from 1 mg to 50 mg.

### Claim 14 (depends on 10)

The method of claim 10 wherein the composition comprises:
a) metformin in an amount of 1,500 mg;
b) taurine in an amount of 125 mg;
c) citrulline in an amount of 60 mg; and
d) methylcobalamin in an amount of 240 μg.

### Claim 15 (depends on 10)

The method of claim 10 wherein the composition comprises:
a) metformin in an amount of 1,500 mg;
b) taurine in an amount of 125 mg;
c) citrulline in an amount of 60 mg;
d) methylcobalamin in an amount of 240 μg; and
e) melatonin in an amount of 25 mg.

### Claim 16 (depends on 10)

The method of claim 10 wherein the amount of taurine is selected from a range that is from 8% to 12% of the amount of metformin by weight.

### Claim 17 (depends on 10)

The method of claim 10 wherein the amount of citrulline is selected from a range that is from 3% to 7% of the amount of metformin by weight.

### Claim 18 (depends on 10)

The method of claim 10 wherein the amount of taurine is selected from a range that is from 150% to 250% of the amount of citrulline by weight.