Filler for separation of enantiomeric isomers in simulated moving bed chromatography

#The present invention relates to a filler for enantiomeric isomer separation, in particular a filler for enantiomeric isomer separation for simulated moving bed chromatography, which is suitable for preparative separation of enantiomeric isomers by simulated moving bed chromatography. The present invention also relates to a method of producing such a filler for separation, to an enantiomeric isomer separation column for simulated moving bed chromatography using such a filler for separation, and to a method of separating enantiomeric isomers using them.

#Organic compounds have many enantiomeric isomers that have exactly the same physical and chemical properties with respect to the boiling point, melting point and solubility but have different physiological activities. Proteins composed of L-amino acids are important constituents of organisms; high-dimensional asymmetric spaces constructed by these proteins recognize organic compounds differently, which results in expression of different physiological activities. In the case of pharmaceuticals, differences in pharmacological activities due to easiness of their binding to specified receptors in an organism have been studied and cases where significant differences in efficacy or toxicity are observed between enantiomeric isomers are well known. Under the circumstances, Guideline for the Production of Pharmaceuticals issued by Ministry of Health, Labour and Welfare describes that “in the case where the drug is of a racemic form, it is desirable that absorption, distribution, metabolism, and excretion kinetics of each isomer be studied in advance”.

#Since as described above the physical and chemical properties of enantiomeric isomers are exactly the same, analysis cannot be performed by ordinary separation means and accordingly studies have been intensely made on a technique for easily and precisely analyzing a wide variety of enantiomeric isomers. As a result, as an analyzing technique that meets these requirements, an optical separation method by high performance liquid chromatography (HPLC), in particular an optical separation method by use of a chiral column for HPLC has been developed. The term “chiral column” as used herein refers to a column with an asymmetry recognition agent (or chiral selector) itself or with a chiral stationary phase composed of a carrier having carried thereon an asymmetry recognition agent. For example, optically active poly(triphenylmethyl methacrylate) (JP 57-150432 A), cellulose or amylose derivative (Y. Okamoto, M. Kawashima and K. Hatada, J. Am. Chem. Soc., 106, 5337, 1984), ovomucoid, which is a protein (JP 63-307829 A) and so on have been developed.

#In the accompanying drawings:

#FIG. 1 is a schematic diagram illustrating one example of simulated moving bed according to the present invention;

#FIG. 2 is a schematic diagram illustrating another example of simulated moving bed according to the present invention;

#In the drawings,

#Reference numerals 1 to 12: chambers containing filler (adsorption chambers), which are connected to each other;

#Reference numeral 13: an eluant feed line;