Method for reducing residual butanol in tetracycline hydrochloride finished product

A technology of tetracycline hydrochloride and tetracycline, which is applied in the field of biology and medicine, can solve the problems of high dissolved concentration of tetracycline urea double salt, fast steam heating speed, and affecting the quality of tetracycline hydrochloride finished products.

Inactive Publication Date: 2021-03-12
NINGXIA QIYUAN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

With this method, because the dissolved concentration of tetracycline urea double salt is too large and the steam heating speed is fast, tetracycline hydrochloride crystals are precipitated rapidly, and the solvent n-butanol is easily wrapped in the crystals, so that the residual n-butanol in the tetracycline hydrochloride finished product reaches more than 2000ppm, which is serious. Affect the finished product quality of tetracycline hydrochloride

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0014] Put 1Kg of tetracycline urea double salt (dried, potency 880u / mg) into a glass reactor, then add 7L of n-butanol (about 20°C), turn on magnetic stirring to stir the solid and liquid evenly to form tetracycline urea double salt and n-butanol Butanol suspension, then slowly drop hydrochloric acid into the reaction kettle through the feed port of the reaction kettle, detect the pH of the solution during the process, stop adding concentrated hydrochloric acid when the pH of the solution reaches 1.75, and the solution is clear, and detect the solution unit 125700u / ml . After suction filtering the solution, put it into a glass crystallization kettle with an interlayer, start the crystallization kettle to stir, inject 60°C hot water into the interlayer of the crystallization kettle through a peristaltic pump, add 70ml of purified water in 10 minutes, and then check the crystallization kettle every 5 minutes Control the rotation speed of the peristaltic pump to control the inte...

Embodiment 2

[0016] Put 1Kg of tetracycline urea double salt (dried, potency 880u / mg) into a glass reactor, then add 8L of n-butanol (about 20°C), turn on magnetic stirring to stir the solid and liquid evenly to form tetracycline urea double salt and n-butanol Butanol suspension, then slowly drop concentrated hydrochloric acid into the reaction kettle through the feed port of the reaction kettle, detect the pH of the solution in the process, stop adding concentrated hydrochloric acid when the pH of the solution reaches 1.75, and the solution is clear, and detect the solution unit 107480u / ml. After the solution is suction-filtered, put it into a glass crystallization kettle with an interlayer, start the crystallization kettle to stir, inject 70°C hot water into the interlayer of the crystallization kettle through a peristaltic pump, add 60ml of purified water at 10 minutes, and check the crystallization kettle every 5 minutes Material temperature, control the number of rotations of the per...

Embodiment 3

[0018] Put 1Kg of tetracycline urea double salt (dried, potency 880u / mg) into a glass reactor, then add 9L of n-butanol (about 20°C), turn on magnetic stirring to stir the solid and liquid evenly to form tetracycline urea double salt and n-butyl For suspension of alcohol, slowly drop concentrated hydrochloric acid into the reaction kettle through the feeding port of the reaction kettle. During the process, the pH of the solution is detected. When the pH of the solution reaches 1.75 and the solution is clear, stop adding concentrated hydrochloric acid. The unit of the solution is 97570u / ml. Vacuum filter the solution, put it into a glass crystallization kettle with an interlayer, start the crystallization kettle to stir, inject 80°C hot water into the interlayer of the crystallization kettle through a peristaltic pump, add 50ml of purified water at 10 minutes, and check the crystallization kettle every 5 minutes Material temperature, control the number of rotations of the perist...

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PUM

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Abstract

The invention relates to a method for reducing residual n-butyl alcohol in a tetracycline hydrochloride finished product, and the method is characterized in that the method the following steps: mixingtetracycline urea double salt and n-butyl alcohol to form a suspension, slowly dropwise adding concentrated hydrochloric acid until the pH value is 1.5-3 and the solution is clear, carrying out suction filtration, performing heating with hot water at 60-70 DEG C for crystallization, and adding purified water at the beginning of crystallization; performing cooling to 25-28 DEG C, carrying out suction filtration, performing washing with acetone, and performing drying. According to the method, a steam heating mode in a traditional tetracycline hydrochloride crystallization process is changed into a hot water heating mode, the feeding ratio of tetracycline urea double salt to n-butyl alcohol and the unit of a dissolved solution are strictly controlled, and purified water is added to adjust the polarity of a solvent when tetracycline hydrochloride crystallization starts, so the crystallization speed is controlled; the influence on the quality of a finished product due to the fact that solvent n-butyl alcohol is wrapped in crystals caused by rapid crystallization of tetracycline hydrochloride is avoided. According to the method disclosed by the invention, the residual butanol in the tetracycline hydrochloride finished product can be reduced to 500ppm or below under the condition that the yield is not influenced.

Description

technical field [0001] The invention relates to the technical fields of biology and medicine, in particular to a method for reducing residual butanol in tetracycline hydrochloride finished products. Background technique [0002] The current salt-forming crystallization process of tetracycline hydrochloride is as follows: use 5 times of n-butanol (L) to make a suspension of tetracycline urea double salt (dry Kg), add reagent grade concentrated hydrochloric acid to adjust the pH to 1.5-2.0 to dissolve and clarify, dissolve The concentration of the solution is 180,000-220,000 u / ml, and the solution starts to form salt and crystallize after being filtered by a plate frame or a suction filter tank. The crystallization is divided into three stages: the heating stage, using the interlayer steam of the crystallization tank to heat up, and 30-50 minutes to dissolve the urea solution. The temperature rises to 35-40°C; in the heat preservation stage, close the steam inlet and use the w...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C237/26C07C231/24
CPCC07C231/24
Inventor 孙瑞君张志朱娜
Owner NINGXIA QIYUAN PHARMA
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