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 . A solution for oral and/or nasal inhalation, comprising about 5 mg/mL to about 20 mg/mL of a pharmaceutically acceptable salt or ester of cromolyn in the form of solution droplets, the majority of solution droplets having a Mass Median Aerodynamic Diameter (MMAD) of about 2 to about 5 microns, wherein said solution is capable of being delivered using a device that deposits (a) at least 3.0 mg and (b) at least 20% by weight of the administered amount of pharmaceutically acceptable salt or ester of cromolyn to Stage 4 and higher of a Next Generational Pharmaceutical Impactor (NGI) cascade impactor device at a flow rate of 60-80 L/min. 
     
     
         2 . The solution of  claim 1 , wherein the solution comprises about 8.5 mg/mL of the pharmaceutically acceptable salt or ester of cromolyn. 
     
     
         3 . The solution of  claim 1 , wherein the device is a nebulizer selected from the group consisting of a jet nebulizer, an ultrasonic nebulizer, and an electronic nebulizer. 
     
     
         4 . The solution of  claim 1 , wherein the device is an inhalation device that delivers the solution as an aerosol. 
     
     
         5 . The solution of  claim 1 , wherein the solution further comprises one or more pharmaceutically acceptable excipients. 
     
     
         6 . The solution of  claim 1 , wherein the solution is hypotonic or isotonic. 
     
     
         7 .- 8 . (canceled) 
     
     
         9 . The solution of  claim 1 , wherein the solution does not comprise an active ingredient other than the pharmaceutically acceptable salt or ester of cromolyn. 
     
     
         10 . The solution of  claim 1 , wherein the solution does not comprise a non-steroidal anti-inflammatory drug. 
     
     
         11 . The solution of  claim 1 , wherein the solution does not comprise ibuprofen. 
     
     
         12 . A method of delivering cromolyn to a patient in need thereof, the method comprising administering the solution of  claim 1  to the patient via oral and/or nasal inhalation, wherein the solution droplets have a mass median particle size (D50) of less than about 5 microns; and wherein the solution is administered using a device that deposits about 4 mg to about 5 mg of cromolyn to the secondary bronchi at a flow rate of 60-80 L/min. 
     
     
         13 . The method of  claim 12 , wherein the method comprises administering about 17.1 mg to of the pharmaceutically acceptable salt or ester of cromolyn, and wherein said solution optionally comprises one or more pharmaceutically acceptable excipients. 
     
     
         14 . The method of  claim 12 , wherein the device is a nebulizer selected from the group consisting of a jet nebulizer, an ultrasonic nebulizer, and an electronic nebulizer. 
     
     
         15 . The method of  claim 12 , wherein administering comprises suspending the solution droplets into an inhaled gas stream. 
     
     
         16 .- 27 . (canceled) 
     
     
         28 . The method of  claim 12 , wherein said solution is administered at a frequency of one or two times daily. 
     
     
         29 . A method of treating or preventing a disease or disorder in a subject in need thereof, comprising administering the solution of  claim 1 , wherein the disease or disorder is an amyloid-associated condition, an inflammatory lung disease, or an allergic lung disease. 
     
     
         30 . The method of  claim 29 , wherein the disease or disorder is an amyloid-associated condition selected from dementia, a motor neuron disease, and traumatic brain injury. 
     
     
         31 . The method of  claim 29 , wherein the amyloid-associated condition is selected from Alzheimer's disease, diabetes mellitus type 2, Parkinson's disease, amyloid polyneuropathy, amyloid cardiomyopathy, systemic senile amyloidosis, transmissible spongiform encephalopathy, Down's syndrome, Huntington's Disease, medullary carcinoma of the thyroid, atherosclerosis, rheumatoid arthritis, aortic medial amyloid, prolactinoma, familial amyloid polyneuropathy, frontotemporal lobar degeneration-tau, Familial British and Danish dementia, hereditary non-neuropathic systemic amyloidosis, dialysis-related amyloidosis, Finnish amyloidosis, atrial amyloidosis, transthyretin familial amyloidosis, hereditary fibrinogen alpha-chain amyloidosis, lattice corneal dystrophy, amyotrophic lateral sclerosis, and cerebral amyloid angiopathy. 
     
     
         32 . The method of  claim 29 , wherein the disease or disorder is an inflammatory lung disease or an allergic lung disease. 
     
     
         33 . The method of  claim 32 , wherein the inflammatory lung disease or the allergic lung disease is selected from asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), pulmonary fibrosis, and cystic fibrosis.