Claims for Patent: 8,226,975

Summary for Patent: 8,226,975

Title:	Lipid-based compositions of antiinfectives for treating pulmonary infections and methods of use thereof
Abstract:	A system for treating or providing prophylaxis 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):	Weers; Jeff (Belmont, CA)
Assignee:	Insmed Incorporated (Monmouth Junction, NJ)
Application Number:	11/634,343
Patent Claims:	1. A system for treating or providing prophylaxis against a pulmonary infection comprising: a) a pharmaceutical formulation comprising an aminoglycoside encapsulated in a liposome, wherein the formulation is a solution or a suspension, and wherein a lipid component of the liposome consists of electrically neutral lipids, and b) an inhalation delivery device capable of generating an aerosol, wherein the aerosol comprises free aminoglycoside in an amount effective to provide immediate bactericidal activity and encapsulated aminoglycoside in an amount effective to provide sustained bactericidal activity. 2. The system of claim 1, wherein the aminoglycoside is amikacin. 3. The system of claim 1, wherein the aminoglycoside is gentamicin. 4. The system of claim 1, wherein the aminoglycoside is tobramycin. 5. The system of claim 1, wherein the liposome comprises a mixture of unilamellar vesicles and multilamellar vesicles. 6. The system of claim 1, wherein the electrically neutral lipids consist of an electrically neutral phospholipid and a sterol. 7. The system of claim 1, wherein the electrically neutral lipids consist of a phosphatidylcholine and a sterol. 8. The system of claim 1, wherein the electrically neutral lipids consist of dipalmitoylphosphatidylcholine (DPPC) and cholesterol. 9. The System of claim 1, wherein the electrically neutral lipids consist of dipalmitoylphosphatidylcholine (DPPC) and cholesterol. 10. The system of claim 1, wherein the aminoglycoside is amikacin, the electrically neutral lipids consist of DPPC and cholesterol, and the liposome comprises a mixture of unilamellar vesicles and multilamellar vesicles. 11. The system of claim 1, wherein a ratio by weight of free aminoglycoside to the aminoglycoside encapsulated in the liposome is between about 1:100 and about 100:1. 12. The system of claim 1, wherein a ratio by weight of free aminoglycoside to the aminoglycoside encapsulated in the liposome is between about 1:10 and about 10:1. 13. The system of claim 1, wherein a ratio by weight of free aminoglycoside to the aminoglycoside encapsulated in the liposome is between about 1:2 and about 2:1. 14. A method for providing prophylaxis against a pulmonary infection in a patient comprising administering an aerosolized pharmaceutical formulation to the lungs of the patient, with the system of claim 1. 15. The method of claim 14, wherein the method first comprises determining the minimum inhibitory concentration (MIC) of the aminoglycoside for inhibiting pulmonary infections, and wherein the amount of free aminoglycoside is at least 2 times the MIC. 16. The method of claim 15, wherein the amount of free aminoglycoside is at least 4 times the MIC. 17. The method of claim 15, wherein the amount of free aminoglycoside is at least 10 times the MIC. 18. The method of claim 15, wherein the ratio of the area under a lung concentration/time curve to the MIC at 24 hours is greater than 25. 19. The method of claim 15, wherein the ratio of the area under a lung concentration/time curve to the MIC at 24 hours is greater than 100. 20. The method of claim 15, wherein the ratio of the area under a lung concentration/time curve to the MIC at 24 hours is greater than 250. 21. The method of claim 14, wherein the aminoglycoside is amikacin. 22. The method of claim 14, wherein the aminoglycoside is gentamicin. 23. The method of claim 14, wherein the aminoglycoside is tobramycin. 24. The method of claim 14, wherein the liposome comprises a mixture of unilamellar vesicles and multilamellar vesicles. 25. The method of claim 14, wherein the electrically neutral lipids comprise a phosphatidylcholine and a sterol. 26. The method of claim 14, wherein the electrically neutral lipids comprise dipalmitoylphosphatidylcholine (DPPC) and a sterol. 27. The method of claim 14, wherein the electrically neutral lipids comprise dipalmitoylphosphatidylcholine (DPPC) and cholesterol. 28. The method of claim 25, wherein the liposome comprises a mixture of unilamellar vesicles and multilamellar vesicles. 29. The method of claim 14, wherein the ratio by weight of free aminoglycoside to aminoglycoside encapsulated in the liposome is between about 1:1.00 and about 100:1. 30. The method of claim 14, wherein the ratio by weight of free aminoglycoside to aminoglycoside encapsulated in the liposome is between about 1:10 and about 10:1. 31. The method of claim 14, wherein the ratio by weight of free aminoglycoside to aminoglycoside encapsulated in the liposome is between about 1:2 and about 2:1. 32. The method of claim 14, wherein the aerosolized pharmaceutical formulation is administered at least once a week. 33. The method of claim 14, wherein the pulmonary infection is selected from the group consisting of chronic obstructive pulmonary disease (COPD), bronchi ectasis, bacterial pneumonia, acute bronchial exacerbations of chronic bronchitis (ABECB), Mycobacterium tuberculosis, Mycobacterium leprae, Mycobacterium africanum, Mycobacterium asiaticum, Mycobacterium avium-intracellulaire, Mycobacterium chelonei abscessus, Mycobacterium fallax, Mycobacterium fortuitum, Mycobacterium kansasii, Mycobacterium leprae, Mycobacterium malmoense, Mycobacterium shimoidei, Mycobacterium simiae, Mycobacterium szulgai, Mycobacterium xenopi, infections caused by inhaled agents of bioterror, and opportunistic fungal infections. 34. The system according to claim 1, wherein the solution is an aqueous solution. 35. The method of claim 33, wherein the patient has cystic fibrosis.