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A kind of biapenem compound and its preparation method

A technology for biapenem and compounds, which is applied in the field of biapenem compounds and their purification, and can solve the problems of low purity of biapenem

Inactive Publication Date: 2011-12-07
HAINAN MEILAN SMITH KLINE PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] How to improve the purity of biapenem is an urgent problem to be solved
In order to overcome the defect of low purity of biapenem prepared in the prior art, the present invention provides a biapenem compound and a method for refining and purifying it

Method used

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  • A kind of biapenem compound and its preparation method
  • A kind of biapenem compound and its preparation method
  • A kind of biapenem compound and its preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045]Take 10 g of crude biapenem prepared according to the synthetic route 1 of the background art, and the content of biapenem was determined to be 92% by high performance liquid chromatography. Dissolve the crude biapenem in 80ml of water and stir thoroughly to dissolve the biapenem. Then add 0.4 g of activated carbon, keep warm at 40°C, stir for 15 min, filter and decarbonize, and collect the filtrate.

[0046] Add 50ml of a mixed solution of methanol and phosphate buffer (pH 4.0) with a volume ratio of 0.05:1 to the above filtrate, and add it to the top of the silica gel column. The filler is a fine hole with a particle size of 100-175 μm and a pore size of 30-50A Silica gel, column length 20cm, diameter 3cm, column pressure 1.0Pa. Then pump the mixed solution of methanol and phosphate buffer (pH4.0) with a volume ratio of 0.05:1 to carry out column chromatography. Collect in sections to obtain the eluate containing biapenem.

[0047] The obtained biapenem aqueous solu...

Embodiment 2

[0050] Take 10 g of crude biapenem prepared according to the synthetic route 2 of the background technology, and the content of biapenem was determined to be 93% by high performance liquid chromatography. Dissolve the crude biapenem in 100ml of water and stir thoroughly to dissolve the biapenem, then add 1.0g of activated carbon, keep warm at 30°C, stir for 30min, filter and decarbonize, and collect the filtrate.

[0051] Add 60ml of a mixed solution of methanol and phosphate buffer (pH4.0) with a volume ratio of 0.12:1 to the above filtrate, and add it to the top of the silica gel column. Pore ​​silica gel, column length 20cm, diameter 3cm, column pressure 2.5Pa. Then pump the mixed solution of 0.12:1 methanol and phosphate buffer (pH4.0) in volume ratio to carry out column chromatography. Collect in sections to obtain the eluate containing biapenem.

[0052] The obtained biapenem aqueous solution was raised to 55-65°C for concentration. Then add ethanol and acetone mixed ...

Embodiment 3

[0055] Take 10 g of biapenem raw material with a long production date (Hebei Zhongrun Pharmaceutical Co., Ltd. of CSPC, batch number: 20080907), and the content of biapenem was determined to be 96% by high performance liquid chromatography. Dissolve the crude product of biapenem in 120ml of water, stir thoroughly to dissolve the biapenem, then add 0.9g of activated carbon, keep warm at 35°C, stir for 20min, filter and decarbonize, and collect the filtrate.

[0056] Add 70ml of a mixed solution of methanol and phosphate buffer (pH4.0) with a volume ratio of 0.1:1 to the above filtrate, and add it to the top of the silica gel column. Pore ​​silica gel, column length 20cm, diameter 3cm, column pressure 1.8Pa. Then pump the mixed solution of 0.1:1 methanol and phosphate buffer (pH4.0) in volume ratio to carry out column chromatography. Collect in sections to obtain the eluate containing biapenem.

[0057] Raise the obtained biapenem aqueous solution to 70-80°C for concentration....

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Abstract

The invention relates to a biapenem compound and a preparation method thereof, which comprises the following steps: 1) dissolving crude biapenem in water, then adding activated carbon, keeping warm, fully stirring, filtering the deactivated carbon, and collecting the filtrate; 2) dissolving The filtrate obtained in the previous step is separated and purified by column chromatography, and the eluent is collected; 3) the temperature is increased to concentrate the above-mentioned eluent solution, and then adding ethanol and acetone with a volume ratio of 1: 0.5~2 mixed solvent solvent, and control temperature for crystallization, the precipitated crystals are centrifuged, washed, and dried to obtain a refined biapenem compound; 4) Optionally, the crystallization mother liquor is returned to step 3), that is, added to the eluting solution obtained in step 2) together with a mixed solvent. By adopting the method of the invention, the purity of crude biapenem can be greatly improved, the quality of preparation products can be improved, and toxic and side effects can be reduced.

Description

technical field [0001] The invention relates to a biapenem compound and a method for purifying it, belonging to the technical field of medicine. Background technique [0002] Biapenem, chemical name: (-)6-[[(4R,5S,6S)-2-carboxy-6-[(1R)-1-hydroxyethyl]-4-methyl- 7-Oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]thio]-6,7-dihydro-5H-pyrazol[1,2-a][1,2 , 4] triazole-4-inner salt, the molecular formula is: C 15 h 18 N 4 o 4 S, molecular weight: 350.40, structural formula: [0003] [0004] Biapenem is a salt-like white or off-white powder that is soluble in water but insoluble in common organic solvents. Biapenem is a 1β-methyl carbapenem antibiotic for injection developed by Lederle Corporation of Japan and Cyamide Corporation of the United States. It was approved for marketing in Japan in March 2002. Biapenem exerts an antibacterial effect by inhibiting the synthesis of cell walls, has broad-spectrum antibacterial activity against gram-positive and gram-negative bacteria and a...

Claims

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Application Information

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IPC IPC(8): C07D519/06
Inventor 杨明贵
Owner HAINAN MEILAN SMITH KLINE PHARMA
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