Method for preparing imipenem monohydrate crystal

A monohydrate, imipenem technology, applied in organic chemistry and other directions, can solve problems such as solubility that is not involved, and achieve the effects of easy control, high purity, rapidity, and uniform crystallinity

Active Publication Date: 2010-11-24
SHENZHEN HAIBIN PHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Moreover, none of the above-reported preparation methods for the crystallization of imipenem monohydrate involved its solubility

Method used

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  • Method for preparing imipenem monohydrate crystal
  • Method for preparing imipenem monohydrate crystal

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Under nitrogen atmosphere, distilled water (200ml) was heated to 45°C-50°C. The crude imipenem (4.0 g, test = 92%) was added to distilled water, stirred at 45°C-50°C for 2 minutes, 1.2 g of activated carbon was added, and then rapidly cooled to 5°C-10°C. Filter the activated charcoal. Add acetone (100ml) to the filtrate, cool down to -5°C--20°C, and freeze the system. Vigorous stirring was maintained at this temperature for 30 minutes. The temperature of the system was then raised to 5°C-10°C, at which temperature acetone (300ml) was added. Then lower the temperature to 0°C-5°C and stir for 3-4 hours. The crystalline solid was filtered, washed with acetone, and dried under reduced pressure at 40°C for 3-4 hours to obtain white crystal imipenem monohydrate (2.80g, test external standard content 98.5%, dissolution time 10 Second).

[0036] The physical characterization data of the obtained imipenem monohydrate:

[0037] UV max H2O nm: 298

[0038] NMR (δ, D 2 O)...

Embodiment 2

[0041] Under nitrogen atmosphere, distilled water (250ml) was heated to 30°C-35°C. The crude imipenem (4.0 g, test = 92%) was added to distilled water, stirred at 30°C-35°C for 2 minutes, 1.2 g of activated carbon was added, and then rapidly cooled to 5°C-10°C. Filter the activated charcoal. Acetone (125ml) was added to the filtrate, the temperature was lowered to -5°C--20°C, and the system was frozen. Vigorous stirring was maintained at this temperature for 30 minutes. The temperature of the system was then raised to 5°C-10°C, at which temperature acetone (375ml) was added. Then lower the temperature to 0°C-5°C and stir for 3-4 hours. The crystalline solid was filtered, washed with acetone, and dried under reduced pressure at 40°C for 3-4 hours to obtain white crystal imipenem monohydrate (2.40g, external standard content 98.7%, dissolution time 15 Second).

Embodiment 3

[0043] The method of Example 1 was repeated using crude imipenem (4.0 g, assay = 80%) to obtain imipenem monohydrate (2.60 g, assay 98.0%, dissolution time 50 seconds) as white crystals.

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Abstract

The invention relates to a method for preparing an imipenem monohydrate crystal (I), which comprises the following steps of: 1) dissolving the crude product of imipenem in water in the nitrogen atmosphere to obtain solution; 2) performing activated carbon treatment on the solution; 3) adding an organic solvent into the solution and reducing the temperature to make the solution in a solid-liquid mixed state so as to form a crystal nucleus; and 4) raising the temperature to melt the crystal nucleus and adding the organic solvent to crystallize and precipitate imipenem monohydrate so as to obtain the imipenem monohydrate crystal. The method for preparing the imipenem monohydrate crystal does not comprise the step of thickening and dewatering or adding acid or alkali to adjust the pH value, so the method is simpler and effective and is easy to control; and the imipenem monohydrate crystal prepared by the method has the advantages of uniform crystallinity, high purity and quick solubility.

Description

technical field [0001] The invention relates to a method for preparing a compound, in particular to a method for preparing imipenem monohydrate crystals with good solubility. Background technique [0002] Imipenem (imipenem, I) is a carbapenem extended-spectrum β-lactam antibiotic developed by Merck, and it is a compound preparation (commercial product) with organic ion transport inhibitor cilastatin sodium (cilastatin sodium). Name: Taineng) is the first marketed carbapenem β-lactam antibiotic. [0003] Imipenem crystal monohydrate is a relatively stable form of imipenem, and its preparation method has been reported. [0004] Among them, U.S. patents such as US4194047, US4260543, and US4292436 all purify the crude product of imipenem or a solution containing imipenem by column chromatography and then lyophilize to obtain amorphous imipenem, or subsequently crystallize it to obtain Imipenem monohydrate was obtained. Later, Crocker and Connolly etc. also reported the metho...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D477/20C07D477/02
Inventor 任鹏朱喜宗汪小华
Owner SHENZHEN HAIBIN PHARMA
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