# US 10,946,011 B2 · Stable oral liquid formulation of trimetazidine

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- Number: US 10,946,011 B2
- Document ID: US10946011B2
- Status: Granted
- Kind: B2
- Application number: 16/277,986
- Filed: 2019-02-15
- Published: 2019-08-22
- Granted: 2021-03-16
- Earliest claimed: 2018-02-19
- Assignees: Martin Pharmaceuticals, Inc.
- Applicants: Martin Pharmaceuticals Inc.
- Inventors: Thomas MacAllister
- Web page: https://patentgrep.com/patent/US10946011B2

## CPC

- A61K 31/495: having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53})
- A61K 9/0095: {Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches (A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006)}
- A61K 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 47/02: Inorganic compounds
- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
- A61K 47/24: containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- A61K 47/36: Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- 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)

## Abstract

Disclosed is a stable oral liquid pharmaceutical composition of trimetazidine having a pH of about pH 4 to about pH 8, comprising a therapeutically effective amount of trimetazidine or a pharmaceutically acceptable salt thereof, one or more orally acceptable buffers, and one or more orally acceptable preservatives that is effective in said pH range. Also disclosed are methods of treating patients with stable oral liquid pharmaceutical composition. The pharmaceutical composition is particularly suitable for treating a patient having a condition treatable by trimetazidine, such as cirrhosis and renal deficiency, and who has a decreased tolerance for acidic or highly basic oral solutions.

## Claims

### Claim 1

A stable oral liquid pharmaceutical composition of trimetazidine having a pH of pH 5 to pH 7, comprising a therapeutically effective amount of trimetazidine or a pharmaceutically acceptable salt thereof, one or more orally acceptable buffers, and one or more orally acceptable preservatives that is effective in said pH range.

### Claim 2 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the one or more orally suitable buffers comprises a phosphate buffer.

### Claim 3 (depends on 1)

The pharmaceutical composition according to claim 1 which comprises a single orally suitable buffer selected from the group consisting of acetate, carbonate, and phosphate.

### Claim 4 (depends on 3)

The pharmaceutical composition according to claim 3, wherein the pH of the composition is from about 5.5 to about 6.5.

### Claim 5 (depends on 4)

The pharmaceutical composition according to claim 4, wherein the one or more orally acceptable preservatives includes methylparaben.

### Claim 6 (depends on 5)

The pharmaceutical composition according to claim 5, wherein the one or more orally acceptable preservatives includes ethylparaben.

### Claim 7 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the therapeutically effective amount of trimetazidine or a pharmaceutically acceptable salt thereof is less than 5% w/v trimetazidine as free base or a pharmaceutically acceptable salt.

### Claim 8 (depends on 7)

The pharmaceutical composition according to claim 7, wherein the therapeutically effective amount of trimetazidine or a pharmaceutically acceptable salt thereof is from about 0.1% to about 2% w/v trimetazidine as free base or a pharmaceutically acceptable salt.

### Claim 9 (depends on 8)

The pharmaceutical composition according to claim 8, wherein the therapeutically effective amount of trimetazidine or a pharmaceutically acceptable salt thereof is from about 0.1% to about 1% w/v trimetazidine as free base or a pharmaceutically acceptable salt.

### Claim 10 (depends on 9)

The pharmaceutical composition according to claim 9, wherein the therapeutically effective amount of trimetazidine or a pharmaceutically acceptable salt thereof is from about 0.1% to about 0.5% trimetazidine as free base or a pharmaceutically acceptable salt; the one or more orally acceptable buffers is a phosphate buffer; and the one or more orally acceptable preservatives is one or more parabens.

### Claim 11 (depends on 9)

The pharmaceutical composition according to claim 9, wherein the wherein the therapeutically effective amount of trimetazidine or a pharmaceutically acceptable salt thereof is from about 0.1% to about 0.3% trimetazidine as free base or a pharmaceutically acceptable salt; the one or more orally acceptable buffers is a phosphate buffer; and the one or more orally acceptable preservatives is one or more parabens.

### Claim 12 (depends on 1)

A method of treating a condition treatable with trimetazidine in a patient having a said condition and who has a decreased tolerance for acidic or highly basic oral solutions, comprising administering to said patient the composition according to claim 1.

### Claim 13 (depends on 11)

A method of treating a condition treatable with trimetazidine in a patient having a said condition and who has a decreased tolerance for acidic or highly basic oral solutions, comprising administering to said patient the composition according to claim 11.

### Claim 14 (depends on 12)

The method according to claim 12, wherein the patient has liver cirrhosis.

### Claim 15 (depends on 14)

The method according to claim 14, wherein said patient has renal insufficiency.

### Claim 16 (depends on 12)

The method according to claim 12, wherein the therapeutically effective amount of trimetazidine or a pharmaceutically acceptable salt thereof is from about 0.1% to about 1% w/v trimetazidine as free base or a pharmaceutically acceptable salt; and wherein the one or more orally acceptable buffers is a single buffer selected from the group consisting of acetate, carbonate, and phosphate, and wherein the pH is from about 5.5 to about 6.5.

### Claim 17 (depends on 16)

The method according to claim 16, wherein the preservative is a mixture of methylparaben sodium and ethylparaben sodium.