Dry powder formulations and methods for treating pulmonary diseases

Abstract

The present invention is directed toward respirable dry particles for delivery of divalent metal cation salts and/or monovalent cation salts to the respiratory tract and methods for treating a subject having a respiratory disease and/or infection.

What is claimed: 
     
         1 . A respirable dry powder comprising respirable dry particles comprising magnesium lactate, one or more therapeutic agents, and optionally one or more excipients, wherein the respirable dry particles comprise about 20% (w/w) to about 80% (w/w) magnesium lactate, and a total amount of about 20% (w/w) to about 60% (w/w) therapeutic agents; and wherein all components of the respirable dry particles amount to 100 weight percent, wherein the respirable dry particles have a volume median geometric diameter (VMGD) of 10 microns or less, a dispersibility ratio (1/4 bar) of 2.0 or less as measured by laser diffraction (RODOS/HELOS system), and a tap density of greater than 0.4 g/cc. 
     
     
         2 . The respirable dry powder of  claim 1 , wherein the respirable dry particles have a tap density of about 0.5 g/cc to about 1.2 g/cc. 
     
     
         3 . The respirable dry powder of  claim 1 , wherein the one or more additional therapeutic agents are independently selected from the group consisting of LABAs, short-acting beta agonists, corticosteroids, LAMAs, antibiotics, dornase alpha, sodium channel blockers, and combinations thereof. 
     
     
         4 . The respirable dry powder of  claim 1 , wherein the respirable dry powder has a Fine Particle Fraction (FPF) of less than 5.6 microns of at least 45%. 
     
     
         5 . The respirable dry powder of  claim 1 , wherein the excipient is selected from the group consisting of sugars, polysaccharides, sugar alcohols, amino acids, and any combination thereof. 
     
     
         6 . The respirable dry powder of  claim 5 , wherein the excipient is leucine. 
     
     
         7 . The respirable dry powder of  claim 1 , wherein the respirable dry particles have a dispersibility ratio (1/4 bar) of 1.5 or less. 
     
     
         8 . The respirable dry powder of  claim 1 , wherein the respirable dry particles have a VMGD of 5 microns or less. 
     
     
         9 . A method of treating a respiratory disease comprising administering to the respiratory tract of a patient in need thereof an effective amount of a respirable dry powder of  claim 1 . 
     
     
         10 . A method of treating or preventing an infectious disease of the respiratory tract comprising administering to the respiratory tract of a patient in need thereof an effective amount of a respirable dry powder of  claim 1 . 
     
     
         11 . A method of reducing inflammation comprising administering to the respiratory tract of a patient in need thereof an effective amount of a respirable dry powder of  claim 1 . 
     
     
         12 . A method of treating a fungal infection comprising administering to the respiratory tract of a patient in need thereof an effective amount of a respirable dry powder of  claim 1 . 
     
     
         13 . A respirable dry powder comprising respirable dry particles comprising magnesium lactate, one or more therapeutic agents, and optionally one or more excipients, wherein the respirable dry particles comprise about 5% (w/w) to about 40% (w/w) magnesium lactate, and about 60% (w/w) to about 95% (w/w) therapeutic agent(s); and wherein all components of the respirable dry particles amount to 100 weight percent, wherein the respirable dry particles have a volume median geometric diameter (VMGD) of 10 microns or less, a dispersibility ratio (1/4 bar) of 2.0 or less as measured by laser diffraction (RODOS/HELOS system), and a tap density of at least about 0.4 g/cc. 
     
     
         14 . The respirable dry powder of  claim 13 , wherein the respirable dry particles have a tap density of about 0.5 g/cc to about 1.2 g/cc. 
     
     
         15 . The respirable dry powder of  claim 3 , wherein the one or more additional therapeutic agents are independently selected from the group consisting of LABAs, short-acting beta agonists, corticosteroids, LAMAs, antibiotics, dornase alpha, sodium channel blockers, and combinations thereof. 
     
     
         16 . The respirable dry powder of  claim 13 , wherein the respirable dry powder has a Fine Particle Fraction (FPF) of less than 5.6 microns of at least 45%. 
     
     
         17 . The respirable dry powder of  claim 1 , wherein the excipient is selected from the group consisting of sugars, polysaccharides, sugar alcohols, amino acids, and any combination thereof. 
     
     
         18 . The respirable dry powder of  claim 17 , wherein the excipient is leucine. 
     
     
         19 . A method of treating a respiratory disease comprising administering to the respiratory tract of a patient in need thereof an effective amount of a respirable dry powder of  claim 13 . 
     
     
         20 . A method of treating a fungal infection comprising administering to the respiratory tract of a patient in need thereof an effective amount of a respirable dry powder of  claim 13 . 
     
     
         21 . The respirable dry powder of  claim 13 , wherein the respirable dry particles have a dispersibility ratio (1/4 bar) of 1.5 or less. 
     
     
         22 . The respirable dry powder of  claim 13 , wherein the respirable dry particles have a VMGD of 5 microns or less.