Aerosolized fosfomycin/aminoglycoside combination for the treatment of bacterial respiratory infections
AssigneeGilead Sciences, Inc.
InventorsWilliam Baker, David MacLeod
Life of this patent
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Abstract
A fosfomycin plus tobramycin combination formulation for delivery by aerosolization is described. The concentrated fosfomycin tobramycin combination formulation containing an efficacious amount of fosfomycin plus tobramycin is able to inhibit susceptible bacteria. Fosfomycin and tobramycin are formulated separately in a dual ampoule such that when reconstituted, the pH is between 4.5 and 8.0 or as a dry powder. The method for treatment of respiratory tract infections by a formulation delivered as an aerosol having mass medium average diameter predominantly between 1 to 5 μ, produced by a jet or ultrasonic nebulizer (or equivalent) or dry powder inhaler.
Claims14
An aerosol formulation for the treatment of infection caused by bacteria in the respiratory tract of a patient
- said formulation comprising from about 1 mg to about 300 mg of fosfomycin, about 1 mg to about 300 mg of tobramycin, and about 0.5-7 mL of a physiologically suitable solution containing a chloride concentration >30 mM;
- wherein
- said formulation is to be administered by aerosolization using a nebulizer able to produce an aerosol with a predominant particle size distribution between 1 and 5 μm and wherein the weight ratio of fosfomycin to tobramycin is selected from the group consisting of:
- (i) from about 7 parts by weight of fosfomycin to about 3 parts by weight of tobramycin;
- (ii) from about 8 parts by weight of fosfomycin to about 2 parts by weight of tobramycin;
- and (iii) from about 9 parts by weight of fosfomycin to about 1 part by weight of tobramycin.
An aerosol dry powder formulation for the treatment of infection caused by bacteria in respiratory tract of a patient
- said formulation comprising from about 1 mg to about 300 mg of fosfomycin, about 1 mg to about 300 mg tobramycin and wherein the weight ratio of fosfomycin to tobramycin is selected from the group consisting of:
- (i) from about 7 parts by weight of fosfomycin to about 3 parts by weight of tobramycin;
- (ii) from about 8 parts by weight of fosfomycin to about 2 parts by weight of tobramycin;
- and (iii) from about 9 parts by weight of fosfomycin to about 1 part by weight of tobramycin, and pharmaceutically acceptable excipients
- said formulation having a particle size between 1-5μ;
- and
- said formulation adapted to be administered to the pulmonary airway by a dry powder inhaler.
A kit for an aerosol formulation consisting of fosfomycin and tobramycin, comprising a dual ampoule blow-fill seal container wherein said fosfomycin and said tobramycin are separated and individually formulated in solution and pH adjusted such that the fosfomycin solution has a pH between 8 and 13 and said tobramycin solution has a pH between 1 and 6 and the fosfomycin solution consists of from about 1 to about 300 mg of fosfomycin and the tobramycin solution consists of from about 1 to about 300 mg of tobramycin wherein the weight ratio of fosfomycin to tobramycin is selected from the group consisting of:
- (i) from about 7 parts by weight of fosfomycin to about 3 parts by weight of tobramycin;
- (ii) from about 8 parts by weight of fosfomycin to about 2 parts by weight of tobramycin;
- and (iii) from about 9 parts by weight of fosfomycin to about 1 part by weight of tobramycin.
Dependencies are inferred from the claim text.