An Inhalable Rapamycin Formulation for Treating Age-Related Conditions

Abstract

The present invention relates to methods and compositions for anti-aging therapy and for the treatment and prophylaxis of age-related diseases and disorders in a human subject in need of such therapy or treatment, the methods comprising the pulmonary administration to the subject, preferably via inhalation, of composition comprising rapamycin, or a prodrug or derivative thereof.

1 .- 43 . (canceled) 
     
     
         44 . A method for anti-aging therapy or for the treatment and prophylaxis of an age-related disease or disorder in a human subject in need of such therapy or treatment, the method comprising administering to the subject by pulmonary delivery a pharmaceutical dry powder comprising microparticles of rapamycin and particles of a carrier. 
     
     
         45 . The method of  claim 44 , wherein the rapamycin persists in lung tissue in a therapeutically effective amount for at least 12 or 24 hours after pulmonary delivery. 
     
     
         46 . The method of  claim 45 , wherein the lung to blood concentration ratio of the rapamycin at 12 or 24 hours after pulmonary delivery is at least 100. 
     
     
         47 . The method of  claim 44 , wherein the rapamycin is present in the pharmaceutical dry powder in an amount of from 5 to 500 micrograms. 
     
     
         48 . The method of  claim 47 , wherein the amount of rapamycin is from about 0.1% to 20% (w/w), based upon the total weight of the powder. 
     
     
         49 . The method of  claim 45 , wherein the rapamycin is present in the lung tissue in an amount of from 1 ng/g to 1 microgram (ug)/g. 
     
     
         50 . The method of  claim 46 , wherein the rapamycin achieves a blood trough level in the subject of less than 5 ng/ml. 
     
     
         51 . The method of  claim 44 , wherein the microparticles of rapamycin consist of particles having diameters from 0.1 to 10 microns and a mean diameter of from 1 to 5 microns. 
     
     
         52 . The method of  claim 44 , wherein the carrier is selected from the group consisting of arabinose, glucose, fructose, ribose, mannose, sucrose, trehalose, lactose, maltose, starches, dextran, mannitol, lysine, leucine, isoleucine, dipalmitylphosphatidylcholine, lecithin, polylactic acid, poly (lactic-co-glutamic) acid, and xylitol, or mixtures of any of the foregoing. 
     
     
         53 . The method of  claim 44 , wherein the administering is effective to achieve a respirable dose of rapamycin of from 5 to 500 micrograms delivered to the lung. 
     
     
         54 . The method of  claim 44 , wherein the pharmaceutical dry powder is produced by a wet polishing process comprising the steps of preparing an aqueous suspension of the rapamycin, subjecting the rapamycin suspension to microfluidization, and spray-drying the resulting particles to form a dry powder. 
     
     
         55 . The method of  claim 44 , wherein the rapamycin has an isomeric B:C ratio of greater than 30:1 or greater than 35:1. 
     
     
         56 . The method of  claim 44 , wherein the age-related disease or disorder is selected from a cancer, prostate enlargement, cardiovascular disease, stroke, atherosclerosis, hypertension, osteoporosis, insulin-resistance and type II diabetes, Alzheimer's disease, Parkinson's disease, age-related macular degeneration, chronic heart failure, liver failure, chronic kidney disease, kidney failure, and chronic lung disease. 
     
     
         57 . The method of  claim 44 , wherein the age-related disease is a cancer. 
     
     
         58 . The method of  claim 44 , wherein the subject is a geriatric subject. 
     
     
         59 . A pharmaceutical dry powder comprising microparticles of rapamycin and particles of a carrier. 
     
     
         60 . The pharmaceutical dry powder of  claim 59 , wherein rapamycin is present in an amount of from 5 to 500 micrograms. 
     
     
         61 . The pharmaceutical dry powder of  claim 60 , wherein the amount of rapamycin is from about 0.1% to 20% (w/w), based upon the total weight of the powder. 
     
     
         62 . The pharmaceutical dry powder of  claim 60 , wherein the microparticles of rapamycin consist of particles having diameters from 0.1 to 10 microns and a mean diameter of from 1 to 5 microns. 
     
     
         63 . The pharmaceutical dry powder of  claim 60 , wherein the carrier is selected from the group consisting of arabinose, glucose, fructose, ribose, mannose, sucrose, trehalose, lactose, maltose, starches, dextran, mannitol, lysine, leucine, isoleucine, dipalmitylphosphatidylcholine, lecithin, polylactic acid, poly (lactic-co-glutamic) acid, and xylitol, or mixtures of any of the foregoing. 
     
     
         64 . The pharmaceutical dry powder of  claim 60 , wherein the rapamycin has an isomeric B:C ratio of greater than 30:1 or greater than 35:1.