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.

What is claimed is: 
     
         1 . A pharmaceutical composition in the form of an inhalable dry powder comprising microparticles of rapamycin and particles of a carrier. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the amount of rapamycin in the composition is from 0.1% to 20% (w/w) or from 0.25% to 2% (w/w), based upon the total weight of the composition. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the microparticles of rapamycin comprise particles having a Mass Median Aerodynamic Diameter (MMAD) of from 1 to 5 microns. 
     
     
         4 . The pharmaceutical composition of  claim 3 , wherein the microparticles of rapamycin have an MMAD of from 2 to 3 microns. 
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein the carrier is selected from the group consisting of arabinose, glucose, fructose, ribose, mannose, sucrose, trehalose, lactose, maltose, starches, dextran, and mannitol. 
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein the particles of the carrier have diameters ranging from 1 to 200 microns, from 30 to 100 microns, or less than 10 microns. 
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein the carrier is a blend of two different carriers, a first carrier and a second carrier. 
     
     
         8 . The pharmaceutical composition of  claim 7 , wherein the first carrier consists of particles having diameters ranging from 30-100 microns and the second carrier consists of particles having diameters of less than 10 microns. 
     
     
         9 . The pharmaceutical composition of  claim 7 , wherein the carrier consists of a blend of two different lactose carriers. 
     
     
         10 . The pharmaceutical composition of  claim 1 , wherein the rapamycin has an isomeric B:C ratio of greater than 30:1 or greater than 35:1. 
     
     
         11 . The pharmaceutical composition of  claim 1 , wherein the surfactant additive excluded from the composition includes polyethylene glycol (PEG)-fatty acids and PEG-fatty acid mono and diesters, PEG glycerol esters, alcohol-oil transesterification products, polyglyceryl fatty acids, propylene glycol fatty acid esters, sterol and sterol derivatives, polyethylene glycol sorbitan fatty acid esters, polyethylene glycol alkyl ethers, sugar and its derivatives, polyethylene glycol alkyl phenols, polyoxyethylene-polyoxypropylene (POE-POP) block copolymers, sorbitan fatty acid esters, ionic surfactants, fat-soluble vitamins and their salts, water-soluble vitamins and their amphiphilic derivatives, amino acids and their salts, and organic acids and their esters and anhydrides. 
     
     
         12 . A pharmaceutical composition in the form of an inhalable dry powder consisting essentially of microparticles of rapamycin and particles of a carrier, wherein the microparticles of rapamycin consist of particles having a Mass Median Aerodynamic Diameter (MMAD) of from 1 to 5 microns. 
     
     
         13 . The pharmaceutical composition of  claim 12 , wherein the carrier is a lactose carrier or a blend of two different lactose carriers. 
     
     
         14 . The pharmaceutical composition of  claim 13 , wherein the microparticles of rapamycin have an MMAD of from 2 to 3 microns. 
     
     
         15 . The pharmaceutical composition of  claim 14 , wherein the surfactant additive excluded from the composition includes polyethylene glycol (PEG)-fatty acids and PEG-fatty acid mono and diesters, PEG glycerol esters, alcohol-oil transesterification products, polyglyceryl fatty acids, propylene glycol fatty acid esters, sterol and sterol derivatives, polyethylene glycol sorbitan fatty acid esters, polyethylene glycol alkyl ethers, sugar and its derivatives, polyethylene glycol alkyl phenols, polyoxyethylene-polyoxypropylene (POE-POP) block copolymers, sorbitan fatty acid esters, ionic surfactants, fat-soluble vitamins and their salts, water-soluble vitamins and their amphiphilic derivatives, amino acids and their salts, and organic acids and their esters and anhydrides. 
     
     
         16 . The composition of  claim 1 , wherein the amount of the rapamycin in the composition is an amount effective to produce a concentration of drug in the lung tissue of from 1 ng/g to 1 ug/g. 
     
     
         17 . The composition of  claim 12 , wherein the amount of the rapamycin in the composition is an amount effective to produce a concentration of drug in the lung tissue of from 1 ng/g to 1 ug/g. 
     
     
         18 . The composition of  claim 1 , wherein the amount of the rapamycin composition is an amount that produces a blood trough level in the subject of less than 5 ng/ml, less than 2 ng/ml, less than 1 ng/ml, less than 0.5 ng/ml, or less than 0.25 ng/ml. 
     
     
         19 . The composition of  claim 12 , wherein the amount of the rapamycin composition is an amount that produces a blood trough level in the subject of less than 5 ng/ml, less than 2 ng/ml, less than 1 ng/ml, less than 0.5 ng/ml, or less than 0.25 ng/ml.