Claims for Patent: 8,802,137

Summary for Patent: 8,802,137

Title:	Sustained release of antiinfectives
Abstract:	Provided are lipid antiinfective formulations substantially free of anionic lipids with a lipid to antiinfective ratio is about 1:1 to about 4:1, and a mean average diameter of less than about 1 μm. Also provided is a method of preparing a lipid antiinfective formulation comprising an infusion process. Also provided are lipid antiinfective formulations wherein the lipid to drug ratio is about 1:1 or less, about 0.75:1 or less, or about 0.50:1 or less prepared by an in line fusion process. The present invention also relates to a method of treating a patient with a pulmonary infection comprising administering to the patient a therapeutically effective amount of a lipid antiinfective formulation of the present invention. The present invention also relates to a method of treating a patient for cystic fibrosis comprising administering to the patient a therapeutically effective amount of a lipid antiinfective formulation of the present invention.
Inventor(s):	Lawrence T. Boni, Brian S. Miller, Vladimir Malinin, Xingong Li
Assignee:	Insmed Inc
Application Number:	US12/748,756
Patent Claims:	1. A liposomal aminoglycoside formulation comprising a liposome having a lipid bilayer and an aminoglycoside encapsulated therein, wherein the lipid bilayer comprises a neutral phospholipid and a sterol, the weight ratio of lipid to aminoglycoside in the formulation is 2:1 or less, and the liposome has a mean diameter of 0.1 microns to 0.5 microns. 2. The liposomal aminoglycoside formulation of claim 1, wherein the aminoglycoside is selected from the group consisting of amikacin, gentamicin, and tobramycin. 3. The liposomal aminoglycoside formulation of claim 1, wherein the aminoglycoside is amikacin. 4. The liposomal aminoglycoside formulation of claim 1, wherein the aminoglycoside is gentamicin. 5. The liposomal aminoglycoside formulation of claim 1, wherein the aminoglycoside is tobramycin. 6. The liposomal aminoglycoside formulation of claim 1, wherein the neutral phospholipid is dipalmitoylphosphatidylcholine (DPPC). 7. The liposomal aminoglycoside formulation of claim 1, wherein the sterol is cholesterol. 8. The liposomal aminoglycoside formulation of claim 1, wherein the neutral phospholipid is DPPC, and the sterol is cholesterol. 9. The liposomal aminoglycoside formulation of claim 1, wherein the aminoglycoside is amikacin, the neutral phospholipid is DPPC and the sterol is cholesterol. 10. The liposomal aminoglycoside formulation of claim 1, wherein the aminoglycoside is an aminoglycoside sulfate. 11. The liposomal aminoglycoside formulation of claim 1, wherein the aminoglycoside is amikacin sulfate. 12. The liposomal aminoglycoside formulation of claim 1, wherein the aminoglycoside is tobramycin sulfate. 13. The liposomal aminoglycoside formulation of claim 1, wherein the aminoglycoside is gentamicin sulfate. 14. A method of treating a patient for a pulmonary infection comprising administering to the patient a therapeutically effective amount of the liposomal aminoglycoside formulation of claim 1. 15. The method of claim 14, wherein the pulmonary infection is a Pseudomonas, staphylococcal, streptococcal, Escherichia, Kiebsiella, Enterobacter, Serratia, Haemophilus, Yersinia, Burkholderia, or mycobacterial infection. 16. A method of treating a cystic fibrosis patient for a pulmonary infection comprising administering to the cystic fibrosis patient a therapeutically effective amount of the liposomal aminoglycoside formulation of claim 1. 17. The method of claim 16, wherein the pulmonary infection is a Pseudomonas, staphylococcal, streptococcal, Escherichia, Kiebsiella, Enterobacter, Serratia, Haemophilus, Yersinia, Burkholderia, or mycobacterial infection. 18. The method of claim 15, wherein the pulmonary infection is a mycobacterial infection. 19. The method of claim 17, wherein the pulmonary infection is a mycobacterial infection. 20. The method of claim 18, wherein the mycobacterial infection is Mycobacterium tuberculosis, Mycobacterium avium complex (MAC) (Mycobacterium avium and Mycobacterium intracellulare), Mycobacterium kansasii, Mycobacterium xenopi, Mycobacterium marinum, Mycobacterium ulcerans, or Mycobacterium fortuitum complex (M. fortuitum and M chelonae). 21. The method of claim 19, wherein the mycobacterial infection is Mycobacterium tuberculosis, Mycobacterium avium complex (MAC) (Mycobacterium avium and Mycobacterium intracellulare), Mycobacterium kansasii, Mycobacterium xenopi, Mycobacterium marinum, Mycobacterium ulcerans, or Mycobacterium fortuitum complex (M. fortuitum and M. chelonae). 22. The method of claim 15, wherein the pulmonary infection is a Pseudomonas infection. 23. The method of claim 16, wherein the pulmonary infection is a chronic Pseudomonas infection. 24. The method of claim 17, wherein the pulmonary infection is a Pseudomonas infection. 25. The method of claim 22, wherein the Pseudomonas infection is a Pseudomonas aeruginosa infection. 26. The method of claim 22, wherein the Pseudomonas infection is a Pseudomonas aeruginosa infection. 27. The method of claim 14, wherein the weight ratio of lipid to aminoglycoside is 0.75:1 or less. 28. The method of claim 15, wherein the weight ratio of lipid to aminoglycoside is 0.75:1 or less. 29. The method of claim 16, wherein the weight ratio of lipid to aminoglycoside is 0.75:1 or less. 30. The method of claim 17, wherein the weight ratio of lipid to aminoglycoside is 0.75:1 or less. 31. The method of claim 18, wherein the weight ratio of lipid to aminoglycoside is 0.75:1 or less. 32. The method of claim 22, wherein the weight ratio of lipid to aminoglycoside is 0.75:1 or less. 33. The method of claim 23, wherein the weight ratio of lipid to aminoglycoside is 0.75:1 or less. 34. The method of claim 24, wherein the weight ratio of lipid to aminoglycoside is 0.75:1 or less. 35. The method of claim 25, wherein the weight ratio of lipid to aminoglycoside is 0.75:1 or less. 36. The method of claim 14, wherein the weight ratio of lipid to aminoglycoside is about 2:1 to about 0.5:1. 37. The method of claim 15, wherein the weight ratio of lipid to aminoglycoside is about 2:1 to about 0.5:1. 38. The method of claim 16, wherein the weight ratio of lipid to aminoglycoside is about 2:1 to about 0.5:1. 39. The method of claim 17, wherein the weight ratio of lipid to aminoglycoside is about 2:1 to about 0.5:1. 40. The method of claim 18, wherein the weight ratio of lipid to aminoglycoside is about 2:1 to about 0.5:1. 41. The method of claim 22, wherein the weight ratio of lipid to aminoglycoside is about 2:1 to about 0.5:1. 42. The method of claim 23, wherein the weight ratio of lipid to aminoglycoside is about 2:1 to about 0.5:1. 43. The method of claim 24, wherein the weight ratio of lipid to aminoglycoside is about 2:1 to about 0.5:1. 44. The method of claim 25, wherein the weight ratio of lipid to aminoglycoside is about 2:1 to about 0.5:1. 45. The method of claim 14, wherein the weight ratio of lipid to aminoglycoside is about 1:1 to about 0.5:1. 46. The method of claim 15, wherein the weight ratio of lipid to aminoglycoside is about 1:1 to about 0.5:1. 47. The method of claim 16, wherein the weight ratio of lipid to aminoglycoside is about 1:1 to about 0.5:1. 48. The method of claim 17, wherein the weight ratio of lipid to aminoglycoside is about 1:1 to about 0.5:1. 49. The method of claim 18, wherein the weight ratio of lipid to aminoglycoside is about 1:1 to about 0.5:1. 50. The method of claim 22, wherein the weight ratio of lipid to aminoglycoside is about 1:1 to about 0.5:1. 51. The method of claim 23, wherein the weight ratio of lipid to aminoglycoside is about 1:1 to about 0.5:1. 52. The method of claim 24, wherein the weight ratio of lipid to aminoglycoside is about 1:1 to about 0.5:1. 53. The method of claim 25, wherein the weight ratio of lipid to aminoglycoside is about 1:1 to about 0.5:1. 54. A nebulized spray comprising the liposomal aminoglycoside formulation of claim 1. 55. A nebulized spray comprising the liposomal aminoglycoside formulation of claim 3. 56. A nebulized spray comprising the liposomal aminoglycoside formulation of claim 6. 57. A nebulized spray comprising the liposomal aminoglycoside formulation of claim 7. 58. A nebulized spray comprising the liposomal aminoglycoside formulation of claim 8. 59. A nebulized spray comprising the liposomal aminoglycoside formulation of claim 9.