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Levolactate ulifloxacin crystal and preparation method and application thereof

A technology of ulifloxacin and crystals, which is applied in the field of new crystals of levo-ulifloxacin lactate, can solve problems such as unstable properties, unstable water content, strong moisture absorption, etc., and achieve good reproducibility, good clinical application potential, The effect of simple preparation method

Active Publication Date: 2012-07-18
GUANGZHOU PHARMACEUTICAL INDUSTRIAL RESEARCH INSTITUTE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] However, the above-mentioned L-ulifloxacin crystal A has obvious disadvantages such as the following in the field of pharmaceutical industry: poor stability, which is reflected in strong hygroscopicity, and leads to insufficient stability of water content, which in turn leads to inaccurate stoichiometry in the preparation process, and properties Unstable, easy to produce decomposition products; strong static electricity, which makes some preparation process steps (such as sieving, bottling, etc.) difficult to operate

Method used

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  • Levolactate ulifloxacin crystal and preparation method and application thereof
  • Levolactate ulifloxacin crystal and preparation method and application thereof
  • Levolactate ulifloxacin crystal and preparation method and application thereof

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preparation example Construction

[0058] Specifically, the preparation method adopted in the present invention can exemplarily include:

[0059] 1. (S)-6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-1H,4H-[1,3]thiazetidine[3,2 -a] the preparation of quinoline-3-carboxylic acid (levo-ulifloxacin)

[0060] 105 grams of racemic ulifloxacin were dissolved in 1500 ml of dimethyl sulfoxide, and a dimethyl sulfoxide solution of 405 ml of D-tartaric acid (27 grams) was added dropwise with stirring, turbidity and precipitation occurred, and stirred at room temperature for 20 hours; Filtration, the obtained solid was dried under vacuum to obtain 86 g, and the solid was recrystallized and purified in dimethyl sulfoxide to obtain (S)-6-fluoro-1-methyl-4-oxo-7-(1- Piperazinyl)-1H, 4H-[1,3]thiazetidino[3,2-a]quinoline-3-carboxylic acid-D-tartrate 37 grams. Add this salt into water to form a suspension, adjust the pH value to 7-8 with 2% NaOH aqueous solution under stirring, and filter and dry the precipitate to obtain (S)-6-fl...

Embodiment 1

[0071] Preparation of L-ulifloxacin Lactate Crystal A (prepared with reference to the method of Chinese invention patent application CN200810027211.9)

[0072]At room temperature 20°C, add 30ml of water to the reaction flask, add 2.1 grams of lactic acid while stirring, and then add 5 grams of (S)-6-fluoro-1-methyl-4-oxo-7-(1-piperazine base)-1H, 4H-[1,3]thiazetidino[3,2-a]quinoline-3-carboxylic acid, after stirring for 60 minutes to obtain a substantially clear solution, adding (S)-6 -Fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-1H,4H-[1,3]thiazetidino[3,2-a]quinoline-3 5% of the weight of the carboxylic acid was decolorized by activated carbon for 30 minutes and then filtered, and the filtrate was added dropwise with 200 ml of absolute ethanol within 1 hour under stirring, at this time, a solid was precipitated, and the stirring was continued for 2 hours, the solid was filtered, and vacuum-dried at 60°C to obtain 4.0 grams Lactic acid (S)-6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl...

Embodiment 2

[0075] Preparation of L-ulifloxacin Lactate Crystal B

[0076] At room temperature, add 150ml of water to the reaction flask, add 14.7 grams of lactic acid under stirring, and then add 35 grams of (S)-6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl) -1H, 4H-[1,3]thiazetidino[3,2-a]quinoline-3-carboxylic acid, add (S)-6-fluoro-1-methyl-4-oxo -7-(1-piperazinyl)-1H, 4H-[1,3]thiazetidin[3,2-a]quinoline-3-carboxylic acid weight of 5% activated carbon 50 ℃ insulation Stir for 30 minutes to decolorize and filter, evaporate the filtrate to remove the solvent under reduced pressure, add 100ml of ethanol, filter, collect the solid and dry it in vacuum at 60°C to obtain 34 grams of lactic acid (S)-6-fluoro-1-methyl-4-oxo-7 Crude -(1-piperazinyl)-1H,4H-[1,3]thiazetidino[3,2-a]quinoline-3-carboxylic acid.

[0077] 5 grams of lactic acid (S)-6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-1H,4H-[1,3]thiazetidine[3, 2-a] Quinoline-3-carboxylic acid crude product, 0.25 g of activated carbon, 100 ml of ...

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Abstract

The invention provides a levolactate ulifloxacin crystal. The crystal has the following peaks shown as 2theta in an X-ray powder diffraction pattern in which Cu-Kalpha radiation is used: 5.1+ / -0.2 degrees, 10.3+ / -0.2 degrees and 25.6+ / -0.2 degrees. The invention further provides a preparation method of the crystal, a medicinal composition comtaining the crystal, and pharmaceutical applications of the crystal and the medicinal composition. The crystal provided by the invention has high repeatability, and the preparation method is simple and rapid. As proved by an experiment, the crystal is superior to the conventional crystal of the compound on the aspects of solubility, stability, hydroscopic property and in-vivo treatment effect, can be prepared into multiple dosage forms, and has high clinical application potential.

Description

technical field [0001] The present invention relates to a new crystal of L-ulifloxacin lactate, a preparation method thereof, a pharmaceutical composition containing the new crystal and their use in preparing medicines for treating infectious diseases. Background technique [0002] Lactate L-ulifloxacin is a fluoroquinolone drug, its chemical name is: lactic acid (S)-6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-1H, 4H -[1,3]thiazetidino[3,2-a]quinoline-3-carboxylic acid (structural formula 1), its bactericidal mechanism is to take the DNA of bacteria as the target, by hindering the DNA topological Constructase prevents bacterial DNA from forming supercoils, further causing irreversible damage to chromosomes, resulting in the inability of bacterial cells to divide and reproduce. [0003] [0004] Compared with the racemate, levo-ulifloxacin has stronger activity and lower toxicity, so it has broad application prospects in the field of biomedicine. Levo-ulifloxacin lactate h...

Claims

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Application Information

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IPC IPC(8): C07D513/04C07C59/08C07C51/43A61K31/496A61P31/00
Inventor 彭锋应军王玉平倪庆纯林丽薇郑浩君陈洁斌冯颂延
Owner GUANGZHOU PHARMACEUTICAL INDUSTRIAL RESEARCH INSTITUTE