Pharmaceutical co-crystal composition and use thereof

Abstract

The current invention relates to series of co-crystals of platinum analogues and their pharmaceutical use. The co-crystals of the subject invention may be used in the treatment or prevention of cancers and virus infections.

1 - 31 . (canceled) 
     
     
         32 . A co-crystal comprising a platinum analogue of formula Pt-02: 
       
         
           
           
               
               
           
         
         and a diacid selected from the group consisting of: 
       
       
         
           
           
               
               
           
         
       
     
     
         33 . The co-crystal of  claim 32 , wherein the diacid is selected from the group consisting of formulas CF-01, CF-02, and CF-08. 
     
     
         34 . The co-crystal of  claim 32 , which is
 a co-crystal comprising the platinum analogue of formula Pt-02 and the diacid of formula CF-02 and having an XRPD pattern comprising peaks at diffraction angles 2-Theta of 7.3°, 9.4°, 10.1°, 12.5°, 13.6° and 23.4°±0.2, an XRPD pattern comprising peaks as set forth in  FIG. 14  or an XRPD pattern substantially similar to the pattern as set forth in  FIG. 14 ; or   a co-crystal comprising the platinum analogue of formula Pt-02 and the diacid of formula CF-08 and having an XRPD pattern comprising peaks at diffraction angles 2-Theta of 7.9°, 11.9°, 14.5°, 15.8°, 17.0°, 17.4° and 17.8°±0.2, an XRPD pattern comprising peaks as set forth in  FIG. 17  or an XRPD pattern substantially similar to the pattern as set forth in  FIG. 17 .   
     
     
         35 . The co-crystal of  claim 32 , which is a co-crystal comprising the platinum analogue of formula Pt-02 and the diacid of formula CF-01 and having an XRPD pattern comprising peaks at diffraction angles 2-Theta of 7.1°, 9.2°, and 10.1°±0.2. 
     
     
         36 . The co-crystal of  claim 32 , which is a co-crystal comprising the platinum analogue of formula Pt-02 and the diacid of formula CF-08 and having an XRPD pattern comprising peaks as set forth in  FIG. 15  or an XRPD pattern substantially similar to the pattern as set forth in  FIG. 15 . 
     
     
         37 . A pharmaceutical composition comprising the co-crystal of  claim 32 . 
     
     
         38 . A pharmaceutical composition comprising the co-crystal of  claim 34 . 
     
     
         39 . A pharmaceutical composition comprising the co-crystal of  claim 35 . 
     
     
         40 . A pharmaceutical composition comprising the co-crystal of  claim 36 . 
     
     
         41 . The pharmaceutical composition of  claim 37 , which is an aqueous composition, wherein the co-crystal is dissolved or dispersed in a pharmaceutically acceptable carrier or aqueous media. 
     
     
         42 . The pharmaceutical composition of  claim 37 , further comprising a therapeutic agent or adjuvant therapy agent selected from the group consisting of folic acid, coenzyme Q10, curcumin, glutathione (GSH), aloe vera, oryzanol, 5-fluorouracil, and bortezomib. 
     
     
         43 . A method of treating cancer in a subject in need thereof, comprising administering to the subject the pharmaceutical composition of  claim 37 , wherein the co-crystal is in a therapeutically effective amount. 
     
     
         44 . A method of treating cancer in a subject in need thereof, comprising administering to the subject the pharmaceutical composition of  claim 39 , wherein the co-crystal is in a therapeutically effective amount. 
     
     
         45 . A method of treating cancer in a subject in need thereof, comprising administering to the subject the pharmaceutical composition of  claim 40 , wherein the co-crystal is in a therapeutically effective amount. 
     
     
         46 . The method of  claim 43 , wherein the cancer is prostate cancer, colorectal cancer, or renal adenocarcinoma. 
     
     
         47 . A method of preparing a co-crystal comprising:
 a) mixing a platinum analogue and a diacid in water,   b) slurrying or stirring the mixture from step a) for a sufficient period of time to form a co-crystal of the platinum analog and the diacid; and optionally   c) isolating the co-crystal,   wherein the platinum analog is a platinum analogue of formula Pt-02:   
       
         
           
           
               
               
           
         
         and the diacid is selected from the group consisting of: 
       
       
         
           
           
               
               
           
         
       
     
     
         48 . The method of  claim 47 , wherein the molar ratio of the platinum analogue to the diacid is in range of 1:0.1 to 1:20. 
     
     
         49 . The method of  claim 48 , wherein the diacid is CF-01. 
     
     
         50 . The co-crystal produced by the method of  claim 47 . 
     
     
         51 . The co-crystal produced by the method of  claim 49 .