Method for preparing high-purity pseudo-polymorphic lavo-ofloxacin hemihydrate

A technology of levofloxacin and hydrate, which is applied in the field of preparation of high-purity polymorphic levofloxacin hemihydrate, can solve the problems of unfavorable quality and yield of finished levofloxacin hemihydrate, difficult microbial degradation, complicated operation procedures, etc. The effect of recovery, good solubility and simple operation process

Inactive Publication Date: 2009-11-11
ZHEJIANG JINGXIN PHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0012] Through the analysis of the above patent documents, it is concluded that there are mainly the following defects: first, the operating procedures in the industrial production process are relatively complicated, and the production cycle is relatively long; , and it is difficult to recycle; thirdly, using halogenated hydrocarbons, DMSO and DMA as organic solvents, it is not only difficult for microorganisms to degrade when discharged into wastewater, but also inhibits or even poisons the growth of microorganisms; fourthly, using polar solvents that are too strong Purifying the crude product of levofloxacin with an organic solvent that is too weak in polarity is detrimental to the quality and yield of the finished product of levofloxacin hemihydrate

Method used

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  • Method for preparing high-purity pseudo-polymorphic lavo-ofloxacin hemihydrate
  • Method for preparing high-purity pseudo-polymorphic lavo-ofloxacin hemihydrate
  • Method for preparing high-purity pseudo-polymorphic lavo-ofloxacin hemihydrate

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Experimental program
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Effect test

Embodiment 1

[0026] Embodiment 1 ethanol: water (85: 15, w / w)

[0027] Put 20g of levofloxacin crude product into a reaction bottle equipped with a reflux device, then add 170g of ethanol and 30g of water, add 2g of activated carbon after heating and dissolving, reflux for decolorization for 45 minutes, suction filter while it is hot, and use 15g of alcohol with a moisture content of 15%. (w / w) Rinse the carbon cake, combine the filtrates, cool down and crystallize under stirring conditions, vacuum filter, rinse the product with 15g of refrigerated alcohol (w / w) with a moisture content of 15%, and vacuum dry at 60-65°C for 8 hours , 17.3 g (86.5%) of pseudopolymorph levofloxacin hemihydrate was obtained.

Embodiment 2

[0028] Embodiment 2 methanol: water (90: 10, w / w)

[0029] Put 20g of levofloxacin crude product into a reaction flask equipped with a reflux device, then add 180g of ethanol and 20g of water, add 2g of activated carbon after heating and dissolving, reflux for decolorization for 45 minutes, suction filter while it is hot, and use 15g of methanol with a moisture content of 10%. (w / w) Rinse the carbon cake, combine the filtrates, cool down and crystallize under stirring conditions, vacuum filter, rinse the product with 15g of frozen methanol (w / w) with a moisture content of 10%, and vacuum dry at 60-65°C for 8 hours , 16.9 g (84.5%) of pseudopolymorphic levofloxacin hemihydrate was obtained.

Embodiment 3

[0030] Embodiment 3 Ethanol: tetrahydrofuran: water (70: 15: 15, w / w / w)

[0031] Put 20g of levofloxacin crude product into a reaction bottle equipped with a reflux device, then add 140g of ethanol, 30g of tetrahydrofuran and 30g of water, heat and dissolve, then add 2g of activated carbon, reflux for decolorization for 45 minutes, suction filter while it is hot, and use 15g of the same proportioning Rinse the charcoal cake with a mixed solvent, combine the filtrates, cool down and crystallize under stirring conditions, vacuum filter, rinse the product with 15 g of the frozen mixed solvent, and vacuum dry for 10 hours at 55-60 ° C to obtain 17.0 g (85.0%) of pseudopolymorphs type levofloxacin hemihydrate.

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Abstract

The invention discloses a method for preparing high-purity pseudo-polymorphic lavo-ofloxacin hemihydrate. The existing method adopts organic solvents with over-strong polarity and over-weak polarity to purify a crude lavo-ofloxacin product so as to be not beneficial to the quality and the recovery rate of a finished lavo-ofloxacin hemihydrate product. The organic solvents have higher boiling points, consume more energy when being recovered and are difficult to recover. Under a heating condition, the crude lavo-ofloxacin product is dissolved in a mixed solvent system consisting of two or more solvents, wherein one solvent in the solvent system is water accounting for 2-25 percent of total weight of the solvent system. A counter solvent is added to crystallize by cooling or during cooling, and an obtained crystallized product is dried to prepare the high-purity pseudo-polymorphic lavo-ofloxacin hemihydrate with a single crystalline form. The mixed solvent containing water and having moderate polarity, low boiling point, easy recovery and small energy consumption is adopted by the method, thus the purity of the product is high, and the bioavailability of the lavo-ofloxacin hemihydrate preparation is high after the lavo-ofloxacin hemihydrate preparation is taken by a person.

Description

technical field [0001] The invention relates to a preparation method of high-purity pseudopolymorph levofloxacin hemihydrate. Background technique [0002] Levofloxacin (Levofloxacin) is a high-efficiency, broad-spectrum, low-toxic antibacterial fluoroquinolone drug developed by Japan's Daiichi Pharmaceutical Company. Its chemical name is (-)-(S)-9-fluoro-2,3-dihydro-3 -Methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3,-de]-[1,4]benzoxazine-6- Carboxylic acid (CAS Registry No. 100986-85-4), structural formula as shown in I. [0003] [0004] Levofloxacin with structural formula I is a strong water-absorbing agent and is extremely unstable during preparation, storage and transportation. Anhydrous levofloxacin of a certain crystalline form is easy to absorb water and will be transformed into pseudopolymorphic levofloxacin hemihydrate (II) and monohydrate (III) respectively, while the appearance gradually changes from white powder to light yellow crystalline powder....

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D498/06A61P31/04
Inventor 张永塘陈翔刘卫省盛利飞
Owner ZHEJIANG JINGXIN PHARMA
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