Claims for Patent: 8,679,532

Summary for Patent: 8,679,532

Title:	Lipid-based compositions of antiinfectives for treating pulmonary infections and methods of use thereof
Abstract:	A system for treating or providing prophylaxus against a pulmonary infection is disclosed comprising: a) a pharmaceutical formulation comprising a mixture of free antiinfective and antiinfective encapsulated in a lipid-based composition, and b) an inhalation delivery device. A method for providing prophylaxis against a pulmonary infection in a patient and a method of reducing the loss of antiinfective encapsulated in a lipid-based composition upon nebulization comprising administering an aerosolized pharmaceutical formulation comprising a mixture of free antiinfective and antiinfective encapsulated in a lipid-based composition is also disclosed.
Inventor(s):	Jeff Weers
Assignee:	Insmed Inc
Application Number:	US13/664,181
Patent Claims:	1. A method for treating or providing prophylaxis against a mycobacterial infection in a patient comprising, administering to the lungs of the patient an aerosolized pharmaceutical formulation comprising an aminoglycoside encapsulated in a liposome, wherein the lipid component of the liposome consists of electrically neutral lipids, the pharmaceutical formulation is a solution or a suspension, and the aerosol comprises free aminoglycoside in an amount effective to provide immediate bactericidal activity against the mycobacterial infection and liposomal encapsulated aminoglycoside in an amount effective to provide sustained bactericidal activity against the mycobacterial infection, wherein the aerosolized pharmaceutical formulation is administered to the lungs of the patient with an inhalation delivery device capable of generating an aerosol. 2. The method of claim 1, wherein the aminoglycoside is amikacin. 3. The method of claim 1, wherein the aminoglycoside is gentamicin, kanamycin, neomycin, netilmicin, streptomycin, tobramycin or paromomycin. 4. The method of claim 1, wherein the electrically neutral lipids comprise a phosphatidylcholine and a sterol. 5. The method of claim 1, wherein the electrically neutral lipids comprise a dipalmitoylphosphatidylcholine (DPPC) and a sterol. 6. The method of claim 1, wherein the electrically neutral lipids comprise a dipalmitoylphosphatidylcholine (DPPC) and cholesterol. 7. The method of claim 1, wherein the mycobacterial infection is a Mycobacterium abscessus. 8. The method of claim 1, wherein the mycobacterial infection is a Mycobacterium avium-intracellulaire. 9. The method of claim 1, wherein the liposome comprises a mixture of unilamellar vesicles and multilamellar vesicles. 10. The method of claim 1, wherein the electrically neutral lipids consist of an electrically neutral phospholipid and a sterol. 11. The method of claim 1, wherein the aminoglycoside is amikacin, the electrically neutral lipids consist of dipalmitoylphosphatidylcholine (DPPC) and cholesterol, and the liposome comprises a mixture of unilamellar vesicles and multilamellar vesicles. 12. The method of claim 1, wherein the ratio by weight of free aminoglycoside to the aminoglycoside encapsulated in the liposome is between about 1:100 and about 100:1. 13. The method of claim 1, wherein the ratio by weight of free aminoglycoside to the aminoglycoside encapsulated in the liposome is between about 1:10 and about 10:1. 14. The method of claim 1, wherein the ratio by weight of free aminoglycoside to the aminoglycoside encapsulated in the liposome is between about 1:2 and about 2:1. 15. The method of claim 1, wherein the pharmaceutical formulation is an aqueous solution or suspension. 16. The method of claim 1, wherein the pharmaceutical formulation is administered at least once per week. 17. The method of claim 1, wherein the ratio of the area under a lung concentration/time curve to the MIC at 24 hours is greater than 25. 18. The method of claim 2, wherein the electrically neutral lipids consist of an electrically neutral phospholipid and a sterol. 19. The method of claim 2, wherein the electrically neutral lipids consist of a phosphatidylcholine and a sterol. 20. The method of claim 2, wherein the electrically neutral lipids consist of a dipalmitoylphosphatidylcholine (DPPC) and a sterol. 21. The method of claim 2, wherein the electrically neutral lipids consist of a dipalmitoylphosphatidylcholine (DPPC) and cholesterol. 22. The method of claim 2, wherein the ratio by weight of free amikacin to the amikacin encapsulated in the liposome is between about 1:100 and about 100:1. 23. The method of claim 2, wherein the ratio by weight of free amikacin to the amikacin encapsulated in the liposome is between about 1:10 and about 10:1. 24. The method of claim 2, wherein the ratio by weight of free amikacin to the amikacin encapsulated in the liposome is between about 1:2 and about 2:1. 25. The method of claim 2, wherein the pharmaceutical formulation is an aqueous solution or suspension. 26. The method of claim 2, wherein the mycobacterial infection is a Mycobacterium abscessus. 27. The method of claim 2, wherein the mycobacterial infection is a Mycobacterium avium-intracellulaire. 28. The method of claim 2, wherein the liposome comprises a mixture of unilamellar vesicles and multilamellar vesicles. 29. The method of claim 2, wherein the pharmaceutical formulation is administered at least once per week. 30. The method of claim 2, wherein the ratio of the area under a lung concentration/time curve to the MIC at 24 hours is greater than 25.