Crystals of 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione

Abstract

The invention relates to type A crystal of 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione characterized to have characteristic absorption peaks (2θ) at 11.5°±0.3°, 14.5°±0.2°, 16.2°±0.3°, 17.0°±0.3°, 17.7°±0.20, 18.6°±0.3°, 19.1°±0.2°, 21.3°±0.4°, 22.4°±0.5°, 25.7°±0.5° and 28.3°±0.5° in a powder X-ray diffraction pattern, and also to a method for preparation thereof, and a pharmaceutical composition comprising the same. The crystal is excellent in stability, and has advantages in handling, storage, and pharmaceutical preparation. The invention also relates to type B, C and D crystals of said compound.

1 . Type A crystal of 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione characterized to have characteristic absorption peaks (2θ) at 11.5°±0.3° in a powder X-ray diffraction pattern.  
     
     
         2 . Type A crystal of 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione characterized to have characteristic absorption peaks (2θ) at 11.5°±0.3° and 25.7°±0.5° in a powder X-ray diffraction pattern.  
     
     
         3 . Type A crystal of 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione characterized to have characteristic absorption peaks (2 0) at 22.4°±0.5° and 25.7°±0.5° in a powder X-ray diffraction pattern.  
     
     
         4 . Type A crystal of 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione characterized to have characteristic absorption peaks (2 0) at 11.5°±0.3° and 22.4°±0.5° in a powder X-ray diffraction pattern.  
     
     
         5 . Type A crystal of 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione characterized to have characteristic absorption peaks (2θ) at 11.5°±0.3°, 17.0°±0.3°, 17.7°±0.2°, 22.4°±0.5° and 25.7°±0.5° in a powder X-ray diffraction pattern.  
     
     
         6 . Type A crystal of 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione characterized to have characteristic absorption peaks (2θ) at 11.5°±0.3°, 14.5°±0.2°, 16.2°±0.3°, 17.0°±0.3°, 17.7°±0.2°, 18.6°±0.3°, 19.1°±0.2°, 21.3°±0.4°, 22.4°±0.5°, 25.7°±0.5° and 28.3°±0.5° in a powder x-ray diffraction pattern.  
     
     
         7 . A method for preparing the type A crystal of 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione according to  claim 1 , which comprises the step of heating and stirring 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione in an alcoholic solvent.  
     
     
         8 . The method according to  claim 7  wherein the alcoholic solvent is an aliphatic alcohol.  
     
     
         9 . The method according to  claim 7  or  claim 8  wherein the alcoholic solvent is an aliphatic alcohol having 1 to 4 carbon atoms.  
     
     
         10 . The method according to any one of  claims 7  to  9  wherein the heating and stirring are carried out under atmospheric pressure or under pressure at a temperature within the range of about 50° C. to refluxing temperature.  
     
     
         11 . A pharmaceutical composition comprising the type A crystal of 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione according to any one of  claims 1  to  6  and a pharmaceutically acceptable carrier.  
     
     
         12 . The pharmaceutical composition according to  claim 11  which is used for therapeutic treatment of diabetes and a complication thereof, hyperlipidemia and a complication thereof, hyperuricemia, leukemia, and pancreatitis.  
     
     
         13 . Type B crystal of 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione characterized to have characteristic diffraction peaks (2θ) at 10.5°±0.5° in a powder X-ray diffraction pattern.  
     
     
         14 . Type B crystal of 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione characterized to have characteristic diffraction peaks (2θ) at 10.5°±0.5° and 20.9°±0.5° in a powder X-ray diffraction pattern.  
     
     
         15 . Type B crystal of 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione characterized to have characteristic diffraction peaks (2θ) at 20.9°±0.5° and 23.0°±0.5° in a powder X-ray diffraction pattern.  
     
     
         16 . Type B crystal of 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione characterized to have characteristic diffraction peaks (2θ) at 10.5°±0.5° and 23.0°±0.5° in a powder X-ray diffraction pattern.  
     
     
         17 . Type B crystal of 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione characterized to have characteristic diffraction peaks (2θ) at 10.5°±0.5°, 20.9°±0.5°, 23.0°±0.5° and 29.2 °±0.5° in a powder X-ray diffraction pattern.  
     
     
         18 . Type B crystal of 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione characterized to have characteristic diffraction peaks (2θ) at 10.5°±0.5°, 18.4°±0.5°, 20.9°±0.5°, 23.0°±0.5°, 26.7°±0.5° and 29.2°±0.5° in a powder X-ray diffraction pattern.  
     
     
         19 . Type C crystal of 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione characterized to have characteristic diffraction peaks (2θ) at 12.5°±0.5° in a powder X-ray diffraction pattern.  
     
     
         20 . Type C crystal of 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione characterized to have characteristic diffraction peaks (2θ) at 12.5°±0.5° and 14.5°±0.5° in a powder X-ray diffraction pattern.  
     
     
         21 . Type C crystal of 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione characterized to have characteristic diffraction peaks (2θ) at 14.5°±0.5° and 22.1°±0.5° in a powder X-ray diffraction pattern.  
     
     
         22 . Type C crystal of 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione characterized to have characteristic diffraction peaks (2θ) at 12.5°±0.5° and 22.1°±0.5° in a powder X-ray diffraction pattern.  
     
     
         23 . Type C crystal of 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione characterized to have characteristic diffraction peaks (2θ) at 12.5°±0.5°, 14.5°±0.5°, 17.6°±0.5° and 22.1°±0.5° in a powder X-ray diffraction pattern.  
     
     
         24 . Type C crystal of 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione characterized to have characteristic diffraction peaks (2 0) at 12.5°±0.5°, 14.5°±0.5°, 17.6°±0.5°, 18.8°±0.5°, 22.1°±0.5°, 25.9°±0.5°, 26.6°±0.5° and 28.3°±0.5° in a powder X-ray diffraction pattern.  
     
     
         25 . Type D crystal of 5-[{G-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione characterized to have characteristic diffraction peaks (2θ) at 17.4°±0.2° and 22.2°±0.2° in a powder X-ray diffraction pattern.  
     
     
         26 . Type D crystal of 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione characterized to have characteristic diffraction peaks (2 0) at 22.2°±0.2° and 25.3°±0.2° in a powder X-ray diffraction pattern.  
     
     
         27 . Type D crystal of 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione characterized to have characteristic diffraction peaks (2θ) at 17.4°±0.2° and 25.3°±0.2° in a powder X-ray diffraction pattern.  
     
     
         28 . Type D crystal of 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione characterized to have characteristic diffraction peaks (2θ) at 10.7°±0.2°, 17.4°±0.2°, 22.2°±0.2° and 25.3°±0.2° in a powder X-ray diffraction pattern.  
     
     
         29 . Type D crystal of 5-[{6-(2-fluorobenzyl)oxy-2-naphthyl}methyl]-2,4-thiazolidinedione characterized to have characteristic diffraction peaks (2θ) at 10.7°±0.2°, 14.5°±0.2°, 15.1°±0.2°, 15.8°±0.2°, 17.4°±0.2°, 18.5°±0.2°, 20.5°±0.2°, 22.2°±0.2°, 25.3°±0.2°, 26.8°±0.2° and 27.8°±0.2° in a powder X-ray diffraction pattern.