Antofloxacin hydrochloride crystallization mode, preparation method and medical composition comprising same

Abstract

The invention relates a crystallization mode of (S)-9-fluorine-2,3-dihydro-3-methyl-8-amino-10-(4-methyl-1-piperazinyl)-7-oxo-7H-naphthyridine[1,2,3-de][1,4]benzoxazine-6-carboxylic hydrochloride and a preparation method thereof. The invention also relates to a crystal medical composition comprising antofloxacin and the application of the composition for treating patients who need antibacterial treatment.

Description

technical field

[0001] The present invention relates to (S)-9-fluoro-2,3-dihydro-3-methyl-8-amino-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyridine A crystalline form of a[1,2,3-de][1,4]benzodiazepine-6-carboxylate hydrochloride and a process for its preparation. The present invention also relates to the pharmaceutical composition containing the crystal form of Antofloxacin and the application of the composition in treating patients needing antibacterial treatment. Background technique

[0002] Antofloxacin hydrochloride is (S)-9-fluoro-2,3-dihydro-3-methyl-8-amino-10-(4-methyl-1-piperazinyl)-7-oxo -7H-pyrido[1,2,3-de][1,4]benzodiazepine-6-carboxylate hydrochloride has the following structure:

[0003]

[0004] Antofloxacin hydrochloride exerts antibacterial effect by interfering with topoisomerase, and is clinically used in the treatment of diseases such as respiratory system infection, urinary system infection, reproductive system infection, skin and soft tissue infection...

Examples

Embodiment 1

[0024] Add 1 gram of Antofloxacin hydrochloride into 30 ml of water, heat to dissolve under stirring, and reflux for 1 hour, then concentrate the filtrate under reduced pressure until a small amount of crystals precipitate, place the precipitated solid at room temperature, and filter out the crystals with suction, at 35°C Dry under vacuum for 20 hours, then expose to ambient humidity to yield 0.9 g.

[0025] The crystal is used as a sample, and powder X-ray powder diffraction is measured to obtain figure 1 X-ray powder diffraction pattern shown.

Embodiment 2

[0027] Add 1 gram of Antofloxacin hydrochloride into 14 milliliters of ethanol-water mixture (40% water content), heat to dissolve under stirring, after reflux for 1 hour, stop heating, stir and cool to room temperature, filter out crystals, 95% Washed twice with ethanol, dried under vacuum at 35°C for 20 hours, and then exposed to ambient humidity to obtain 0.8 g.

[0028] The crystal is used as a sample, and powder X-ray powder diffraction is measured to obtain figure 1 X-ray powder diffraction pattern shown.

Embodiment 3

[0030] Add 0.5 gram of Antofloxacin hydrochloride into 100 milliliters of methanol-water mixture (4% water content), heat to dissolve under stirring, after reflux for 1 hour, stop heating, stir and cool to room temperature for 16 hours, filter out the crystals, Then exposed to ambient humidity for 7 days.

[0031] The crystal is used as a sample, and powder X-ray powder diffraction is measured to obtain figure 1 X-ray powder diffraction pattern shown.

technical field

[0001] The present invention relates to (S)-9-fluoro-2,3-dihydro-3-methyl-8-amino-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyridine A crystalline form of a[1,2,3-de][1,4]benzodiazepine-6-carboxylate hydrochloride and a process for its preparation. The present invention also relates to the pharmaceutical composition containing the crystal form of Antofloxacin and the application of the composition in treating patients needing antibacterial treatment. Background technique

[0002] Antofloxacin hydrochloride is (S)-9-fluoro-2,3-dihydro-3-methyl-8-amino-10-(4-methyl-1-piperazinyl)-7-oxo -7H-pyrido[1,2,3-de][1,4]benzodiazepine-6-carboxylate hydrochloride has the following structure:

[0003]

[0004] Antofloxacin hydrochloride exerts antibacterial effect by interfering with topoisomerase, and is clinically used in the treatment of diseases such as respiratory system infection, urinary system infection, reproductive system infection, skin and soft tissue infection...

Examples

Embodiment 1

[0024] Add 1 gram of Antofloxacin hydrochloride into 30 ml of water, heat to dissolve under stirring, and reflux for 1 hour, then concentrate the filtrate under reduced pressure until a small amount of crystals precipitate, place the precipitated solid at room temperature, and filter out the crystals with suction, at 35°C Dry under vacuum for 20 hours, then expose to ambient humidity to yield 0.9 g.

[0025] The crystal is used as a sample, and powder X-ray powder diffraction is measured to obtain figure 1 X-ray powder diffraction pattern shown.

Embodiment 2

[0027] Add 1 gram of Antofloxacin hydrochloride into 14 milliliters of ethanol-water mixture (40% water content), heat to dissolve under stirring, after reflux for 1 hour, stop heating, stir and cool to room temperature, filter out crystals, 95% Washed twice with ethanol, dried under vacuum at 35°C for 20 hours, and then exposed to ambient humidity to obtain 0.8 g.

[0028] The crystal is used as a sample, and powder X-ray powder diffraction is measured to obtain figure 1 X-ray powder diffraction pattern shown.

Embodiment 3

[0030] Add 0.5 gram of Antofloxacin hydrochloride into 100 milliliters of methanol-water mixture (4% water content), heat to dissolve under stirring, after reflux for 1 hour, stop heating, stir and cool to room temperature for 16 hours, filter out the crystals, Then exposed to ambient humidity for 7 days.

[0031] The crystal is used as a sample, and powder X-ray powder diffraction is measured to obtain figure 1 X-ray powder diffraction pattern shown.

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