Pharmaceutically active ornitihine derivatives, ammonium salts thereof and methods of making same

Abstract

The present invention relates to pharmaceutically active ornithine compounds, particularly to pharmaceutically acceptable ammonium salts of N δ -acyl derivatives of N α (4-amino-4-deoxypteroyl)-L-ornithine compounds; and methods of treatment and pharmaceutical compositions that utilize or comprise one or more of such ammonium salts. The ammonium salts provided by the invention exhibit superior chemical stability than corresponding acidic N δ -acyl derivatives of N δ -acyl derivatives of N α (4-amino-4-deoxypteroyl)-L-ornithine compounds.

1 - 52 . (canceled)  
   
   
       53 . An isolated salt comprising anionic N α -(4-amino-4-deoxypteroyl)-N δ -hemiphthaloyl-L-ornithine (“PT 523”).  
   
   
       54 . The salt of  claim 53 , wherein the salt is an ammonium salt.  
   
   
       55 . The salt of  claim 53 , which is a precipitated salt.  
   
   
       56 . The salt of  claim 53 , which is a lyophilized salt.  
   
   
       57 . The salt of  claim 53 , wherein the salt has a solubility in water equal to or greater than 20 mg/ml.  
   
   
       58 . The salt of  claim 53 , wherein the salt is at least 96.5% pure.  
   
   
       59 . The salt of  claim 53 , wherein the salt is at least 97.3% pure.  
   
   
       60 . A process for producing a composition comprising contacting PT 523 free acid with a base under conditions suitable to produce a PT 523 salt and isolating the PT 523 salt.  
   
   
       61 . The process of  claim 60 , wherein the salt is isolated by precipitation.  
   
   
       62 . The process of  claim 60 , wherein the salt is isolated by lyophilization.  
   
   
       63 . The process of  claim 60 , wherein the salt is isolated in a purity of at least 96.5%.  
   
   
       64 . The process of  claim 60 , wherein the salt is isolated in a purity of at least 97.3%.  
   
   
       65 . The process of  claim 60 , wherein the base comprises an ammonium cation.  
   
   
       66 . A salt produced by the process of  claim 60 .  
   
   
       67 . A pharmaceutical composition comprising a PT 523 salt of  claim 53  and a pharmaceutically acceptable carrier.  
   
   
       68 . The pharmaceutical composition of  claim 67 , wherein the PT 523 salt is an ammonium salt of PT 523.  
   
   
       69 . A dosage unit formulation comprising a PT 523 salt of  claim 53 .  
   
   
       70 . The dosage unit formulation of  claim 69 , wherein the PT 523 salt is an ammonium salt.  
   
   
       71 . A method for the treatment of cancer in a mammal comprising administering an effective amount of the salt of  claim 53  to a mammal in need thereof.