Novel crystal form of pyrrolidylthiocarbapenem derivative

Abstract

Novel crystals of a pyrrolidylthiocarbapenem derivative having excellent stability is provided. According to the present invention, a crystal of (+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3[[(3S,5S)-5-(sulfamoylaminomethyl)pyrrolidin-3-yl]thio]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid having a diffraction pattern in powder X-ray diffraction having main peaks at diffraction angles (2θ) of about 6.62, 13.04, 15.44, 16.58, 17.64, 20.88, 23.26, 25.02 and 25.52 (degrees) are provided.

1 - 4 . (canceled) 
     
     
         5 . A crystal of a dihydrate of (+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3[[(3S,5S)-5-(sulfamoylaminomethyl)pyrrolidin-3-yl]thio]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid having a powder X-ray diffraction pattern with main peaks at diffraction angles (2θ) of about 6.62, 13.04, 15.44, 16.58, 17.64, 20.88, 23.26, 25.02 and 25.52 (degrees). 
     
     
         6 . A method for producing a crystal according to  claim 5 , comprising the steps of:
 (A) dissolving (+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3[[(3S,5S)-5-(sulfamoylaminomethyl)pyrrolidin-3-yl]thio]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid or a hydrate thereof in water;   (B) depositing crystals from the aqueous solution obtained in step (A);   (C) determining the powder X-ray diffraction pattern of the crystals deposited in step (B); and   (D) selecting a crystal having a diffraction pattern with main peaks at diffraction angles (2θ) of about 6.62, 13.04, 15.44, 16.58, 17.64, 20.88, 23.26, 25.02 and 25.52 (degrees).   
     
     
         7 . (canceled) 
     
     
         8 . A method for producing a crystal of a dihydrate of (+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3[[(3S,5S)-5-(sulfamoylaminomethyl)pyrrolidin-3-yl]thio]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid having a powder X-ray diffraction pattern with main peaks at diffraction angles (2θ) of about 6.62, 13.04, 15.44, 16.58, 17.64, 20.88, 23.26, 25.02 and 25.52 (degrees), said method comprising the steps of:
 (A) dissolving (+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3[[(3S,5S)-5-(sulfamoylaminomethyl)pyrrolidin-3-yl]thio]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid or a hydrate thereof in water; 
 (B) placing a seed crystal produced according to  claim 6  or recited in  claim 5  in the aqueous solution obtained in step (A); 
 (C) depositing crystals from the seeded aqueous solution obtained in step (B); and 
 (D) isolating the crystals formed in step (C). 
 
     
     
         9 . A method for producing a crystal of a monohydrate of (+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3[[(3S,5S)-5-(sulfamoylaminomethyl)pyrrolidin-3-yl]thio]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid having a powder X-ray diffraction pattern with main peaks at diffraction angles (2θ) of about 13.04, 14.98, 15.88, 16.62, 20.62, 21.06, 22.18, 23.90, 26.08, 28.22 and 28.98 (degrees), said method comprising the steps of:
 (A) dissolving (+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3[[(3S,5S)-5-(sulfamoylaminomethyl)pyrrolidin-3-yl]thio]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid or a hydrate thereof in water; 
 (B) placing a seed crystal produced according to  claim 6  or recited in  claim 5  in the aqueous solution obtained in step (A); 
 (C) depositing crystals from the seeded aqueous solution obtained in step (B) 
 (D) isolating the crystals formed in step (C); and 
 (E) drying the crystals obtained in step (D). 
 
     
     
         10 . A method for preparing an injectable solution comprising the step of dissolving the crystal according to  claim 5  or the crystal produced by the method according to any one of  claim 6 ,  8  or  9  in a physiologically acceptable agent.