SUSTAINED RELEASE OF ANTIINFECTIVES
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.
1 - 92 . (canceled)
93 . A method of treating a mycobacterial pulmonary infection in a patient in need thereof, comprising,
nebulizing a therapeutically effective amount of a liposomal aminoglycoside composition comprising amikacin, or a pharmaceutically acceptable salt thereof, encapsulated in a liposome having a lipid bilayer comprising a neutral phospholipid and cholesterol, wherein the weight ratio of lipid to the aminoglycoside, or the pharmaceutically acceptable salt thereof, in the composition is 0.75:1 or less, to form a nebulized spray, and
administering the nebulized spray to the patient.
94 . The method of claim 93 , wherein the amikacin, or pharmaceutically acceptable salt thereof is amikacin sulfate.
95 . The method of claim 93 , wherein the neutral phospholipid is a phosphatidylcholine.
96 . The method of claim 94 , wherein the neutral phospholipid is a phosphatidylcholine.
97 . The method of claim 95 , wherein the phosphatidylcholine is dipalmitoylphosphatidylcholine (DPPC).
98 . The method of claim 96 , wherein the phosphatidylcholine is dipalmitoylphosphatidylcholine (DPPC).
99 . The method of claim 93 , 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 ).
100 . The method of claim 94 , 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 ).
101 . The method of claim 95 , 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 ).
102 . The method of claim 96 , 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 ).
103 . The method of claim 97 , 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 ).
104 . The method of claim 98 , 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 ).
105 . The method of claim 99 , wherein the mycobacterial infection is Mycobacterium avium complex (MAC) ( Mycobacterium avium and Mycobacterium intracellulare ).
106 . The method of claim 100 , wherein the mycobacterial infection is Mycobacterium avium complex (MAC) ( Mycobacterium avium and Mycobacterium intracellulare ).
107 . The method of claim 101 , wherein the mycobacterial infection is Mycobacterium avium complex (MAC) ( Mycobacterium avium and Mycobacterium intracellulare ).
108 . The method of claim 102 , wherein the mycobacterial infection is Mycobacterium avium complex (MAC) ( Mycobacterium avium and Mycobacterium intracellulare ).
109 . The method of claim 103 , wherein the mycobacterial infection is Mycobacterium avium complex (MAC) ( Mycobacterium avium and Mycobacterium intracellulare ).
110 . The method of claim 104 , wherein the mycobacterial infection is Mycobacterium avium complex (MAC) ( Mycobacterium avium and Mycobacterium intracellulare ).
111 . The method of claim 93 , wherein the liposome has a mean diameter of about 1 um to about 1.0 um.
112 . The method of claim 111 , wherein the liposome has a mean diameter of about 0.2 μm to about 0.5 μm.