5-CNAC as oral delivery agent for parathyroid hormone fragments

Abstract

Pharmaceutical compositions for the effective oral delivery of a parathyroid hormone, PTH, as well as methods for administration of the compositions are provided. Additionally, methods for stimulating new bone formation and treating and/or preventing osteoporosis are also provided.

1 . A pharmaceutical composition for oral delivery comprising a PTH fragment and N-(5-chlorosalicviovl)-8-aminocaprylic acid and pharmaceutically acceptable salts and esters thereof, said PTH fragment selected from PTH (1-28) to PTH (1-41).  
     
     
         2 . A pharmaceutical composition according to  claim 1  wherein the PTH fragment is selected from PTH (1-28), PTH (1-31), PTH (1-34), PTH (1-37), PTH (1-38) and PTH (1-41).  
     
     
         3 . A pharmaceutical composition according to  claim 1  wherein the PTH fragment is PTH (1-34).  
     
     
         4 . A pharmaceutical composition according to  claim 1  wherein the PTH fragment is recombinant PTH.  
     
     
         5 . A pharmaceutical composition according to  claim 3  wherein the PTH fragment is recombinant PTH.  
     
     
         6 . A pharmaceutical composition according to  claim 1  wherein the PTH fragment is human parathyroid hormone.  
     
     
         7 . A pharmaceutical composition according to  claim 6  wherein the human parathyroid hormone is hPTH (1-34).  
     
     
         8 . A pharmaceutical composition for oral delivery comprising a PTH fragment and a compound selected from the free acid, the disodium salt of N-(5-chlorosalicyloyl)-8-aminocaprylic acid and the monohydrate thereof, said PTH fragment selected from PTH (1-28) to PTH (1-41).  
     
     
         9 . A pharmaceutical composition according to  claim 8  wherein the compound is N-(5-chloro-salicyloyl)-8-aminocaprylic acid.  
     
     
         10 . A pharmaceutical composition for oral delivery comprising a PTH fragment and the disodium salt of N-(5-chloro-salicyloyl)-8-aminocaprylic acid.  
     
     
         11 . A method for orally administering an effective dose of PTH comprising orally administering to a patient in need of PTH a pharmaceutical composition comprising a therapeutically effective amount of a PTH fragment and 5-CNAC, said PTH fragment selected from PTH (1-28)-PTH (1-41).  
     
     
         12 . A method according to  claim 11  wherein the PTH is selected from PTH (1-28), PTH (1-31), PTH (1-34), PTH (1-37), PTH (1-38) and PTH (1-41).  
     
     
         13 . A method according to  claim 11  wherein the PTH is hPTH (1-34).  
     
     
         14 . A method according to  claim 11  wherein the PTH is recombinant PTH.  
     
     
         15 . A method according to  claim 11  wherein the PTH is recombinant hPTH.  
     
     
         16 . A method according to  claim 11  wherein the 5-CNAC is selected from the free acid, the disodium salt of N-(5-chlorosalicyloyl)-8-aminocaprylic acid and the monohydrate thereof.  
     
     
         17 . A method according to  claim 11  wherein the 5-CNAC is N-(5-chloro-salicyloyl)-8-aminocaprylic acid.  
     
     
         18 . A method according to  claim 11  wherein the 5-CNAC is the disodium salt of N-(5-chloro-salicyloyl)-8-aminocaprylic acid.  
     
     
         19 . A method of stimulating new bone formation comprising orally administering to a patient in need of new bone formation a pharmaceutical composition comprising a therapeutically effective amount of a PTH fragment and 5-CNAC, said PTH fragment selected from PTH (1-28)-PTH (1-41).  
     
     
         20 . A method of treatment or prevention of osteoporosis comprising orally administering to a patient in need of said treatment or prevention a pharmaceutical composition comprising a therapeutically effective amount of a PTH fragment and 5-CNAC, said PTH fragment selected from PTH (1-28)-PTH (1-41).  
     
     
         21 . The use of 5-CNAC for the preparation of a pharmaceutical composition suitable for the oral delivery of PTH fragments selected from PTH (1-28)-PTH (1-41).