# US 11,026,941 B2 · Concentrated, inhalable ciprofloxacin formulation

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- Number: US 11,026,941 B2
- Document ID: US11026941B2
- Status: Granted
- Kind: B2
- Application number: 16/540,552
- Filed: 2019-08-14
- Published: 2019-12-26
- Granted: 2021-06-08
- Earliest claimed: 2006-10-24
- Assignees: Grifols, S.A.
- Applicants: Gripols, S.A.
- Inventors: David C. Cipolla; James Blanchard
- Web page: https://patentgrep.com/patent/US11026941B2

## CPC

- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61K 9/0043: {Nose}
- A61K 9/0073: {Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; (nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M)}
- 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 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/22: Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
- A61P 11/08: Bronchodilators
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61K 9/5084: {Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs (tablets containing such a mixture A61K9/2077)}
- 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

A concentrated inhalable formulation of an antibiotic drug such as ciprofloxacin is disclosed. The antibiotic is formulated with sodium acetate and liposome which incorporate antibiotic. The formulation is aerosolized and inhaled for treatment of respiratory tract infections and other medical conditions.

## Claims

### Claim 1

A method of treating bronchiectasis in a patient, comprising:
administering to lungs of the patient an aerosolized formulation comprising:
free unencapsulated ciprofloxacin;
a pharmaceutically acceptable excipient; and
liposome-encapsulated ciprofloxacin wherein the liposomes are unilamellar, have an average particle size of 1 nanometer to 10 microns, and comprise cholesterol and hydrogenated soy phosphatidyl-choline (HSPC);
wherein the liposomes maintain integrity when aerosolized and provide a ciprofloxacin release rate of 0.5% to 20% per hour over a period of time of 1-12 hours.

### Claim 2 (depends on 1)

The method of claim 1, wherein the liposomes have a diameter in a range from 20 nanometers to 1 micron.

### Claim 3 (depends on 2)

The method of claim 2, wherein the free unencapsulated ciprofloxacin comprises between about 1 and about 75% of the total free unencapsulated and liposome-encapsulated ciprofloxacin.

### Claim 4 (depends on 1)

The method of claim 1, wherein the liposomes provide a ciprofloxacin release rate of 2% to 10% per hour over a period of time of 1-6 hours.

### Claim 5 (depends on 1)

The method of claim 1, wherein the aerosolized formulation further comprises an isotonic histidine buffer.

### Claim 6 (depends on 1)

The method of claim 1, wherein the aerosolized formulation has a pH of 6.0.

### Claim 7 (depends on 1)

The method of claim 1, wherein the aerosolized formulation has an osmolarity of 300 mOsm/kg.

### Claim 8 (depends on 1)

The method of claim 1, wherein the aerosolized formulation further comprises an isotonic histidine buffer at pH 6.0, and an osmolarity of 300 mOsm/kg.

### Claim 9

A method of treating bronchiectasis in a patient, comprising:
administering to lungs of the patient an aerosolized formulation comprising: free unencapsulated ciprofloxacin;
a pharmaceutically acceptable excipient; and
liposome-encapsulated ciprofloxacin wherein the liposomes comprise cholesterol and hydrogenated soy phosphatidyl-choline (HSPC), are unilamellar, 90% or more of the liposomes maintain integrity when aerosolized, and provide a ciprofloxacin release rate of 0.5% to 20% per hour over a period of time of 1-12 hours.

### Claim 10 (depends on 9)

The method of claim 9, wherein the liposomes provide a ciprofloxacin release rate of 2% to 10% per hour over a period of time of 1-6 hours.

### Claim 11 (depends on 9)

The method of claim 9, wherein the liposomes have a diameter in a range from 20 nanometers to 1 micron.

### Claim 12 (depends on 9)

The method of claim 9, wherein the free unencapsulated ciprofloxacin comprises between about 1 and about 75% of the total free unencapsulated and liposome-encapsulated ciprofloxacin.

### Claim 13 (depends on 9)

The method of claim 9, wherein the aerosolized formulation further comprises an isotonic histidine buffer.

### Claim 14 (depends on 9)

The method of claim 9, wherein the aerosolized formulation has a pH of 6.0.

### Claim 15 (depends on 9)

The method of claim 9, wherein the aerosolized formulation has an osmolarity of 300 mOsm/kg.

### Claim 16 (depends on 9)

The method of claim 9, wherein the aerosolized formulation further comprises an isotonic histidine buffer at pH 6.0, and an osmolarity of 300 mOsm/kg.