# US 11,304,897 B2 · Pharmaceutical formulation containing umeclidinium bromide and vilanterol trifenatate

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 11,304,897 B2
- Document ID: US11304897B2
- Status: Granted
- Kind: B2
- Application number: 17/342,781
- Filed: 2021-06-09
- Published: 2021-12-09
- Granted: 2022-04-19
- Earliest claimed: 2020-06-09
- Assignees: Anovent Pharmaceutical (U.S.), LLC
- Applicants: Anovent Pharmaceutical (U.S.), LLC
- Inventors: Cai Gu Huang; Ning He
- Web page: https://patentgrep.com/patent/US11304897B2

## CPC

- A61K 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 9/0078: {for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions}
- A61K 9/12: Aerosols; Foams {(A61K9/0043, A61K9/0056, A61K9/006, A61K9/0073 take precedence; spray-films A61K9/7015)}
- A61K 31/137: Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone}
- A61K 31/138: Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine (atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377)
- A61K 31/439: the ring forming part of a bridged ring system, e.g. quinuclidine (8-azabicyclo [3.2.1] octanes A61K31/46)
- A61K 47/02: Inorganic compounds
- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- A61K 47/186: {Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide}
- 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 47/40: Cyclodextrins; Derivatives thereof
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- 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 present invention relates to a liquid pharmaceutical preparation and a method for administering the pharmaceutical preparation by nebulizing the pharmaceutical preparation in an inhaler. The propellant-free pharmaceutical preparation comprises: (a) active substances selected from umeclidinium bromide and vilanterol trifenatate; (b) a solvent; (c) a pharmacologically acceptable solubilizing agent; (d) a pharmacologically acceptable preservative; and (e) a pharmacologically acceptable stabilizer; and optionally includes other pharmacologically acceptable additives.

## Claims

### Claim 1

A liquid, propellant-free pharmaceutical formulation comprising:
(a) umeclidinium bromide and vilanterol trifenatate;
(b) a solvent;
(c) a pharmacologically acceptable solubilizing agent,
wherein the pH of the formulation ranges from about 2.5 to about 6.

### Claim 2 (depends on 1)

The pharmaceutical formulation of claim 1, wherein the umeclidinium bromide is present in an amount ranging from about 2 mg/100 ml to about 1050 mg/100 ml.

### Claim 3 (depends on 1)

The pharmaceutical formulation of claim 1, wherein the vilanterol trifenatate is present in an amount ranging from about 1 mg/100 ml to about 550 mg/100 ml.

### Claim 4 (depends on 1)

The pharmaceutical formulation of claim 1, wherein the solvent is water.

### Claim 5 (depends on 1)

The pharmaceutical formulation of claim 1, wherein the solubilizing agent is selected from the group consisting of tween-80 and cyclodextrin derivatives.

### Claim 6 (depends on 1)

The pharmaceutical formulation of claim 1, wherein the solubilizing agent is present in an amount ranging from about 1 g/100 ml to about 40 g/100 ml.

### Claim 7 (depends on 6)

The pharmaceutical formulation of claim 6, wherein the solubilizing agent is sulfobutylether β-cyclodextrin in an amount ranging from about 1 g/100 ml to about 40 g/100 ml.

### Claim 8 (depends on 1)

The pharmaceutical formulation of claim 1, further comprising a preservative selected from the group consisting of benzalkonium chloride, benzoic acid, and sodium benzoate.

### Claim 9 (depends on 8)

The pharmaceutical formulation of claim 8, wherein the preservative is present in an amount ranging from about 2 mg/100 ml to about 300 mg/100 ml.

### Claim 10 (depends on 1)

The pharmaceutical formulation of claim 1, further comprising a stabilizer selected from the group consisting of edetic acid, edetate disodium dehydrate, edetate disodium, citric acid, and combinations thereof.

### Claim 11 (depends on 1)

The pharmaceutical formulation of claim 1, wherein the stabilizer is present in an amount ranging from about 1 mg/100 ml to about 500 mg/100 ml.

### Claim 12 (depends on 1)

A method for administering the pharmaceutical formulation of claim 1 comprising nebulizing a defined amount of the pharmaceutical formulation with an inhaler by using pressure to force the pharmaceutical preparation through a nozzle to form an inhalable aerosol.

### Claim 13 (depends on 12)

The method of claim 12, wherein the defined amount of the pharmaceutical formulation is less than about 70 microliters.

### Claim 14 (depends on 12)

The method of claim 12, wherein the mass median aerodynamic diameter (MMAD) of vilanterol trifenatate and umeclidinium bromide are less than about 10 μm.

### Claim 15 (depends on 12)

The method of claim 12, wherein the geometric standard deviation (GSD) of vilanterol trifenatate and umeclidinium bromide are less than about 5%.

### Claim 16 (depends on 12)

The method of claim 12, wherein the aerosol has a particle size distribution having a Dv(10) of less than about 4 μm, a Dv(50) of less than about 7 μm, and a Dv(90) of less than about 12 μm.

### Claim 17 (depends on 12)

The method of claim 12, wherein the pharmaceutical formulation is administered using an inhaler as depicted in FIG. 1.

### Claim 18 (depends on 1)

A method of treating asthma or COPD in a patient, comprising administering to the patient the pharmaceutical formulation of claim 1 by inhalation.

### Claim 19 (depends on 18)

The method of claim 18, wherein the daily dose of umeclidinium bromide is about 15 micrograms to about 110 micrograms and the daily dose of vilanterol trifenatate is about 9 micrograms to about 60 micrograms.

### Claim 20

A liquid, propellant-free pharmaceutical formulation comprising:
an aqueous solution of:
(a) umeclidinium bromide in an amount of about 2 mg/100 mL to about 1050 mg/100 mL of the formulation;
(b) vilanterol trifenatate in an amount of about 1 mg/100 mL to about 550 mg/100 mL of the formulation;
(c) sulfobutylether β-cyclodextrin (SBECD) in an amount of about 1 g/100 mL to about 40 g/100 mL of the formulation;
(d) sodium chloride in an amount of about 100 mg/100 mL to about 900 mg/100 mL of the formulation;
wherein the pH of the solution ranges from about 2.5 to about 6.