Cromolyn compositions and methods thereof

Abstract

Methods of delivering cromolyn to a patient in need thereof, methods of treating amyloid-associated conditions and inflammatory or allergic lung diseases, and packs and kits comprising cromolyn are described.

1 .- 28 . (canceled) 
     
     
         29 . A method of treatment of an amyloidosis-associated condition, comprising administering a composition comprising cromolyn or a pharmaceutically acceptable salt or ester of cromolyn to a subject in need thereof, wherein the amyloidosis-associated condition is selected from:
 diabetes mellitus type 2, Parkinson's disease (PD), idiopathic myeloma, amyloid polyneuropathy, amyloid cardiomyopathy, systemic senile amyloidosis, transmissible spongiform, Down's syndrome, Huntington's disease (HD), medullary carcinoma of the thyroid, rheumatoid arthritis, prolactinoma, familial amyloid polyneuropathy (FAP), frontotemporal lobar degeneration-tau, familial British dementia, familial Danish dementia, hereditary non-neuropathic systemic amyloidosis, dialysis-related amyloidosis, Finnish amyloidosis, atrial amyloidosis, transthyretin familial amyloidosis, hereditary fibrinogen alpha-chain amyloidosis, motor neuron disease, lattice corneal dystrophy, amyotrophic lateral sclerosis, and cerebral amyloid angiopathy.   
     
     
         30 . The method of  claim 29 , comprising administering the composition via pulmonary delivery, nasal inhalation, or oral inhalation. 
     
     
         31 . The method of  claim 29 , wherein the cromolyn or a pharmaceutically acceptable salt or ester of cromolyn is in a form of particles. 
     
     
         32 . The method of  claim 31 , wherein:
 the composition is formulated as a powder for inhalation;   the particles of cromolyn or the pharmaceutically acceptable salt or ester of cromolyn have a Mass Median Aerodynamic Diameter (MMAD) of about 2 to about 5 microns; and   when the composition is delivered to a Next Generation Pharmaceutical Impactor cascade impactor device (NGI) at a flow rate of 20-90 L/min, at least 20% by weight of the administered amount of cromolyn or the pharmaceutically acceptable salt or ester of cromolyn is delivered to Stage 4 or higher of the NGI.   
     
     
         33 . The method of  claim 32 , wherein the composition further comprises one or more pharmaceutically acceptable excipients. 
     
     
         34 . The composition of  claim 29 , wherein the composition comprises about 50% to about 60% (w/w) of the pharmaceutically acceptable salt or ester of cromolyn and about 40% to about 50% of one or more excipients. 
     
     
         35 . The composition of  claim 34 , wherein the excipient is selected from a monosaccharide, a disaccharide, an oligosaccharide, a polysaccharide, a polyalcohol, and lactose. 
     
     
         36 . The composition of  claim 34 , wherein the excipient is selected from lactose, mannitol, and sorbitol. 
     
     
         37 . The method of  claim 29 , wherein cromolyn or the pharmaceutically acceptable salt or ester of cromolyn is formulated as a solution for oral and/or nasal inhalation. 
     
     
         38 . The method of  claim 37 , wherein the solution comprises from about 5 mg/mL to about 20 mg/mL of cromolyn or the pharmaceutically acceptable salt or ester of cromolyn in the form of solution droplets. 
     
     
         39 . The method of  claim 37 , wherein:
 the solution droplets have an MMAD of about 2 to about 5 microns, and   when the solution droplets are delivered to an NGI at a flow rate of 20-90 L/min, at least 20% by weight of the administered amount of cromolyn or the pharmaceutically acceptable salt or ester of cromolyn is delivered to Stage 4 or higher of the NGI.   
     
     
         40 . The method of  claim 29 , comprising administering from about 16.1 mg to about 19.9 mg of cromolyn or the pharmaceutically acceptable salt or ester of cromolyn. 
     
     
         41 . The method of  claim 29 , comprising administering about 17.1 mg of cromolyn or the pharmaceutically acceptable salt or ester of cromolyn. 
     
     
         42 . The method of  claim 29 , wherein the pharmaceutically acceptable salt or ester of cromolyn is cromolyn sodium. 
     
     
         43 . The method of  claim 29 , wherein the pharmaceutically acceptable salt or ester of cromolyn is an ester of cromolyn. 
     
     
         44 . The method of  claim 29 , wherein the pharmaceutically acceptable salt or ester of cromolyn is a methyl, ethyl, propyl, or butyl ester of cromolyn. 
     
     
         45 . The method of  claim 29 , wherein the pharmaceutically acceptable salt or ester of cromolyn is an ethyl or tert-butyl ester of cromolyn.