Novel pharmaceutical salts and polymorphs of a factor xa inhibitor

Abstract

The present invention provides for salts comprising a compound of Formula I and an acid that has activity against mammalian factor Xa. The present invention is also directed to methods of making the compound of Formula I.

1 .- 28 . (canceled) 
     
     
         29 . A method for preventing venous thrombosis in a mammal in need thereof, the method comprising administering to the mammal a therapeutically effective amount of a salt represented by formula II: 
       
         
           
           
               
               
           
         
       
       and aspirin, wherein the salt is in a crystalline form characterized by a powder X-ray diffraction pattern having at least four approximate characteristic peak locations selected from 4.9, 9.7, 13.8, 14.1, 15.2, 17.6, 18.5, 20.8, 21.6, 22.7, 24.1, 26.3, and 26.8 degrees 2θ. 
     
     
         30 . The method of  claim 29 , wherein the salt has a powder X-ray diffraction pattern having at least eight approximate characteristic peak locations selected from 4.9, 9.7, 11.8, 13.8, 14.1, 15.2, 17.6, 18.5, 19.9, 20.8, 21.6, 22.7, 24.1, 25.0, 26.3, and 26.8 degrees 2θ. 
     
     
         31 . The method of  claim 29 , wherein the salt has a powder X-ray diffraction pattern approximate to the powder X-ray diffraction pattern shown in  FIG. 1A . 
     
     
         32 . The method of  claim 29 , wherein the salt has a differential scanning calorimetry approximate to the differential scanning calorimetry pattern shown in  FIG. 2A . 
     
     
         33 . The method  claim 29 , wherein the salt is administered to the mammal in the form of a pharmaceutical composition comprising the salt and a pharmaceutically acceptable carrier. 
     
     
         34 . The method of  claim 33 , wherein the pharmaceutical composition is in capsule form. 
     
     
         35 . The method of  claim 34 , wherein the method comprises administering the capsule once or several times daily. 
     
     
         36 . A method for preventing deep venous thrombosis in a mammal in need thereof, the method comprising administering to the mammal a therapeutically effective amount of a salt represented by formula II: 
       
         
           
           
               
               
           
         
       
       and aspirin, wherein the salt is in a crystalline form characterized by a powder X-ray diffraction pattern having at least four approximate characteristic peak locations selected from 4.9, 9.7, 13.8, 14.1, 15.2, 17.6, 18.5, 20.8, 21.6, 22.7, 24.1, 26.3, and 26.8 degrees 2θ. 
     
     
         37 . The method of  claim 36 , wherein the salt has a powder X-ray diffraction pattern having at least eight approximate characteristic peak locations selected from 4.9, 9.7, 11.8, 13.8, 14.1, 15.2, 17.6, 18.5, 19.9, 20.8, 21.6, 22.7, 24.1, 25.0, 26.3, and 26.8 degrees 2θ. 
     
     
         38 . The method of  claim 36 , wherein the salt has a powder X-ray diffraction pattern approximate to the powder X-ray diffraction pattern shown in  FIG. 1A . 
     
     
         39 . The method of  claim 36 , wherein the salt has a differential scanning calorimetry approximate to the differential scanning calorimetry pattern shown in  FIG. 2A . 
     
     
         40 . The method  claim 36 , wherein the salt is administered to the mammal in the form of a pharmaceutical composition comprising the salt and a pharmaceutically acceptable carrier. 
     
     
         41 . The method of  claim 40 , wherein the pharmaceutical composition is in capsule form. 
     
     
         42 . The method of  claim 41 , wherein the method comprises administering the capsule once or several times daily.