• 专利标题:   Chromatographic column used for purifying tacrolimus, includes lower portion filled with chromatographic medium filler e.g. chromatographic silica gel or aluminum oxide, upper portion filled with mixed filler e.g. graphene powder.
  • 专利号:   CN111450574-A
  • 发明人:   YUE Z, QIN J, WANG X, LIN C
  • 专利权人:   FUZHOU AONIDUO BIOTECHNOLOGY CO LTD
  • 国际专利分类:   B01D015/20, B01D015/22, C07D498/18
  • 专利详细信息:   CN111450574-A 28 Jul 2020 B01D-015/22 202067 Pages: 13 Chinese
  • 申请详细信息:   CN111450574-A CN10056612 22 Jan 2019
  • 优先权号:   CN10056612

▎ 摘  要

NOVELTY - A chromatographic column is divided into upper portion and lower portion. The lower portion of chromatographic column is filled with first chromatographic medium filler. The upper portion of chromatographic column is filled with first mixed filler. The height of first chromatography medium filler at lower portion of the chromatography column accounts for 5-10% of total height of chromatography column filler. The diameter to height ratio of chromatography column is 1:5-25. The first chromatographic medium filler is chromatographic silica gel or aluminum oxide with granularity of 200-500 meshes. The first mixed filler is 1-50 pts. wt. graphene powder and 100 pts. wt. first chromatographic medium filler. The granularity of graphene powder is 500-5000 meshes. USE - The chromatographic column is used for purifying tacrolimus (claimed). ADVANTAGE - The column can absorb olefin structure with unsaturated bond on side chain of tacrolimus and two major analog impurities of tacrolimus including dihydrotacrolimus and ascomycin. It can be separated by chromatography column without olefin or other unsaturated key structure. The method is separates pigment and tacrolimus on chromatographic column, and solves technical problem in industry. DETAILED DESCRIPTION - INDEPENDENT CLAIMS are included for: (1) purification method of tacrolimus comprising dissolving tacrolimus crude product in ethyl acetate, adding non-polar alkane or petroleum ether, preparing first liquid to be separated, loading into chromatographic column, forming first chromatographic column containing tacrolimus, gradient eluting using first eluting solvent, and collecting eluent with greater than or equal to 98% tacrolimus content; (2) chromatographic column dividing into upper portion and lower portion; and (3) purification method of tacrolimus comprising dissolving tacrolimus crude product in ethanol, acetone, methanol or acetonitrile solution, adding water to stir and dilute, preparing second liquid to be separated, loading into chromatographic column, forming second chromatographic column containing tacrolimus, gradient eluting using second eluting solvent, and collecting eluent with greater than or equal to 98% tacrolimus content. The lower portion of chromatographic column is filled with second chromatographic medium filler. The upper portion of chromatographic column is filled with second mixed filler. The height of second chromatography medium filler at lower portion of the chromatography column accounts for 5-10% of total height of chromatography column filler. The diameter to height ratio of chromatography column is 1:10-25. The second chromatographic medium filler is octadecyl-bonded silica gel having granularity of 200-500 meshes, octane-bonded silica gel, cyano-bonded silica gel or phenyl-bonded silica gel. The second mixed filler is 1-50 pts. wt. graphene powder and 100 pts. wt. second chromatographic medium filler. The first eluting solvent is prepared by mixing non-polar alkane or petroleum ether and ethyl acetate.