Filler for separation of enantiomeric isomers in simulated moving bed chromatography

Abstract

The present invention provides a filler having a high productivity suitable for preparative separation by simulated moving bed chromatography. That is, there is provided a filler for enantiomeric isomer separation by simulated moving bed chromatography, which has a porous carrier carrying a polysaccharide derivative thereon and has a TS coefficient in a range of 0.55 to 1.20, the TS coefficient being defined by the below-shown formula (I), abd obtained by using an enantiomeric isomer separation column for simulated moving bed chromatography in which the filler is filled in a column tube by a slurry filling method: TS coefficient=[ Vc−[t ( TS )− t (blank)]× FR]/[t ( TS )− t (blank)]× FR   (I) (wherein abbreviations mean the following: Vc (cm 3 ): a column volume; FR (ml/min.): a flow velocity; t(TS) (min.): an elution time for tetrakis(trimethylsilyl)silane (=TS); and t(blank) (min.): an elution time for TS in the state where the column is not connected).

What is claimed is:  
     
         1 . A filler for enantiomeric isomer separation for simulated moving bed chromatography having a porous carrier carrying a polysaccharide derivative thereon, wherein the filler has a TS coefficient in a range of 0.55 to 1.20, the TS coefficient being defined by the below shown formula (I), obtained by using an enantiomeric isomer separation column for simulated moving bed chromatography in which the filler is filled in a column tube by a slurry filling method:  
         TS  coefficient=[ Vc−[t ( TS )− t (blank)]× FR]/[t ( TS )− t (blank)]× FR    (I)  
       (wherein abbreviations mean the following: 
 Vc (cm 3 ) : a column volume;  
 FR (ml/min.): a flow velocity;  
 t(TS) (min.): an elution time for tetrakis(trimethylsilyl)silane (=TS); and  
 t(blank) (min.) : an elution time for TS in the state where the column is not connected).  
 
     
     
         2 . The filler for enantiomeric isomer separation for simulated moving bed chromatography according to  claim 1 , wherein the TS coefficient is 0.55 to 1.0.  
     
     
         3 . The filler for enantiomeric isomer separation for simulated moving bed chromatography according to  claim 1 , wherein the TS coefficient is above 1.0 and not greater than 1.20.  
     
     
         4 . The filler for enantiomeric isomer separation for simulated moving bed chromatography according to  claim 1 , wherein the porous carrier is silica gel having a particle diameter of 1 μm to 300 μm and an average pore diameter of 200 Angstroms to 8,000 Angstroms.  
     
     
         5 . The filler for enantiomeric isomer separation for simulated moving bed chromatography according to any one of  claims 1  to  4 , wherein the polysaccharide derivative is cellulose ester derivatives, cellulose carbamate derivatives, amylose ester derivatives or amylose carbamate derivatives.  
     
     
         6 . The filler for enantiomeric isomer separation for simulated moving bed chromatography according to  claim 1 , wherein the carrying amount of polysaccharide derivative in the enantiomeric isomer separation filler for simulated moving bed chromatography is 23 to 40% by mass.  
     
     
         7 . The filler for enantiomeric isomer separation for simulated moving bed chromatography according to  claim 1 , wherein the carrying amount of polysaccharide derivative in the enantiomeric isomer separation filler for simulated moving bed chromatography is 25 to 35% by mass.  
     
     
         8 . The filler for enantiomeric isomer separation for simulated moving bed chromatography according to  claim 1 , wherein the filler has an ability of treating a mixture of enantiomeric isomers (racemic form) at a rate such that mass (kg) of racemic form treated per 1 kg of the filler a day is 0.1 to 4 kg-rac./kg-CSP/day.  
     
     
         9 . A method of producing the enantiomeric isomer separation filler for simulated moving bed chromatography according to  claim 1 , comprising coating a porous carrier with a polysaccharide derivative dope in a plurality of times.  
     
     
         10 . An enantiomeric isomer separation column for simulated moving bed chromatography, comprising a column having packed therein the enantiomeric isomer separation filler for simulated moving bed chromatography as set forth in  claim 1 .  
     
     
         11 . The enantiomeric isomer separation column for simulated moving bed chromatography according to  claim 10 , wherein the column has a ratio of column length (L) to column inner diameter (D), L/D, of 0.01 to 100.  
     
     
         12 . A method of separating enantiomeric isomers, comprising performing preparative separation of enantiomeric isomers by simulated moving bed chromatography by using the enantiomeric isomer separation filler for simulated moving bed chromatography as set forth in  claim 1 .  
     
     
         13 . A method of separating enantiomeric isomers, comprising performing preparative separation of enantiomeric isomers by simulated moving bed chromatography by using the enantiomeric isomer separation column for simulated moving bed chromatography as set forth in  claim 10  or  11 .