Refining method of doxycycline hydrochloride

A technology of doxycycline hydrochloride and a refining method, which is applied in the field of chemical substance purification, can solve the problems of increased side effects, low content, and high total impurity content of preparations, and achieve the effects of reducing toxic and side effects, simple refining steps, and improving product quality

Pending Publication Date: 2020-08-18
HAINAN GENERAL & KANGLI PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The impurity greater than 0.1% (high performance liquid chromatography area normalized purity) in the commercially available doxycycline hydrochloride crude drug has β-doxycycline (the impurity A in the European Pharmacopoeia, and the pharmacopoeia stipulates that the impurity content must not exceed 2.0%) and 2-acetyl-2-decarbamide doxycycline (the impurity F in the European Pharmacopoeia, the pharmacopoeia stipulates that the impurity content should not be greater than 2.0%), the excessive content of the above-mentioned impurities will make the total impurity content of the preparation too high , will also seriously affect the quality of doxycycline hydrochloride preparations, and cause side effects to increase; but the physical and chemical properties of impurity A and impurity F are very close to doxycycline, and it is difficult to remove
[0006] Regarding the refined crystallization of doxycycline hydrochloride, absolute ethanol suspension free base has been used to add hydrochloric acid refined crystallization, but the purity of doxycycline hydrochloride obtained by this method is not high; or impurity A or impurity F after refining The content of one of the impurities is significantly reduced, but the content of both impurities cannot be reduced to a lower level at the same time

Method used

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  • Refining method of doxycycline hydrochloride
  • Refining method of doxycycline hydrochloride
  • Refining method of doxycycline hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] A method for refining doxycycline hydrochloride, comprising the steps of:

[0036] Step S1, adding 400 g of raw material doxycycline hydrochloride into a mixed solvent of water and acetone until dissolved, then filtering under reduced pressure to obtain the first filtrate and the first filter residue, washing the first filter residue with a mixed solvent of water and acetone and filtering to obtain the second Two filtrates, the second filtrate is combined with the first filtrate to obtain filtrate; wherein the volume ratio of water and acetone in the mixed solvent of water and acetone is 1:1, wherein the volume mass of the mixed solvent of water and acetone and raw material doxycycline hydrochloride The ratio is 8:1;

[0037] Step S2, control the temperature to 25°C, add concentrated ammonia water to the filtrate obtained in step S1 to adjust the pH to 6.0, stir and lower the temperature to 15°C, keep warm and crystallize, and then centrifugally filter to obtain the fir...

Embodiment 2

[0042] A method for refining doxycycline hydrochloride, comprising the steps of:

[0043] Step S1, adding 400 g of raw material doxycycline hydrochloride into a mixed solvent of water and acetone until dissolved, then filtering under reduced pressure to obtain the first filtrate and the first filter residue, washing the first filter residue with a mixed solvent of water and acetone and filtering to obtain the second Two filtrates, the second filtrate is combined with the first filtrate to obtain filtrate; wherein the volume ratio of water and acetone in the mixed solvent of water and acetone is 2:1, wherein the volume mass of the mixed solvent of water and acetone and raw material doxycycline hydrochloride The ratio is 7:1;

[0044] Step S2, control the temperature at 28°C, add concentrated ammonia water to the filtrate obtained in step S1 to adjust the pH to 6.5, stir and cool down to 18°C, keep warm and crystallize, and then centrifugally filter to obtain the first solid cry...

Embodiment 3

[0049] A method for refining doxycycline hydrochloride, comprising the steps of:

[0050] Step S1, adding 400 g of raw material doxycycline hydrochloride into a mixed solvent of water and acetone until dissolved, then filtering under reduced pressure to obtain the first filtrate and the first filter residue, washing the first filter residue with a mixed solvent of water and acetone and filtering to obtain the second Two filtrates, the second filtrate is combined with the first filtrate to obtain filtrate; wherein the volume ratio of water and acetone in the mixed solvent of water and acetone is 1:2, wherein the volume mass of the mixed solvent of water and acetone and raw material doxycycline hydrochloride The ratio is 9:1;

[0051] Step S2, control the temperature at 23°C, add concentrated ammonia water to the filtrate obtained in step S1 to adjust the pH to 5.5, stir and lower the temperature to 13°C, keep warm and crystallize, and then centrifugally filter to obtain the fir...

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Abstract

The invention discloses a refining method of doxycycline hydrochloride, which belongs to the technical field of chemical substance purification, and comprises the following steps: S1, adding raw materials into a mixed solvent until the raw materials are dissolved clearly, and filtering; S2, adding concentrated ammonia water into the filtrate, stirring, cooling, carrying out heat preservation crystallization, carrying out centrifugal filtration, and drying to obtain a doxycycline solid; S3, adding the doxycycline solid into the mixed solvent to prepare turbid liquid, stirring, controlling the temperature, and dropwise adding a concentrated hydrochloric acid solution; S4, controlling the temperature, stirring, preserving heat, crystallizing, filtering, washing and drying to obtain a refineddoxycycline hydrochloride solid; and S5, crushing the refined doxycycline hydrochloride solid, and packaging to obtain the final product doxycycline hydrochloride. According to the refining method, high-purity doxycycline hydrochloride can be obtained, the refining steps are simple, the product yield is high, the refining method is suitable for industrial large-scale production, and when doxycycline hydrochloride obtained through refining is used for subsequent product preparation, the quality of preparation products can be improved, and toxic and side effects can be reduced.

Description

technical field [0001] The invention relates to doxycycline hydrochloride, in particular to a method for refining doxycycline hydrochloride, which belongs to the technical field of chemical substance purification. Background technique [0002] Doxycycline hydrochloride, the chemical name is 6-methyl-4-(dimethylamino)-3,5,10,12,12a-pentahydroxy-1,11-dioxo-1,4 , 4a, 5, 5a, 6, 11, 12a-octahydro-2-tetracenecarboxamide hydrochloride hemihydrate and hemiethanolate, molecular formula C 22 h 24 N 2 o 8 ·HCl·1 / 2H 2 O 1 / 2C 2 h 5 OH; molecular weight: 512.94, structural formula: [0003] [0004] Doxycycline hydrochloride is a broad-spectrum semi-synthetic tetracycline antibiotic, effective against gram-positive bacteria, gram-negative bacteria and chlamydia, clinically used for respiratory tract infection, biliary tract infection, tonsillitis, lymphadenitis, cellulitis , treatment of chronic bronchitis in the elderly, mycoplasma pneumonia, syphilis, gonorrhea, typhus, chole...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C231/24C07C237/26
CPCC07C231/24C07C2603/46C07C237/26
Inventor 符永红彭先芬符成龙林方育肖汉文
Owner HAINAN GENERAL & KANGLI PHARMA
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