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Preparation method of erythromycin impurity D

A technology for erythromycin and impurities, which is applied in the field of preparation of erythromycin impurity D, can solve the problems of difficulty in obtaining monomer impurities, affecting drug safety, impurity carcinogenicity, etc., to reduce process steps, meet quality research needs, and reaction conditions mild effect

Pending Publication Date: 2020-04-24
PI & PI BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Impurities of erythromycin are a kind of ingredients without any medicinal effect in medicines, and some impurities are carcinogenic and teratogenic. These impurities have adverse reactions, seriously affect the safety of medication, and bring immeasurable risks to drug users
[0004] The preparation process of domestic generic drugs is diverse, resulting in different impurities. Different from the original research drug, the content and type of impurities will also be different. However, domestic research on the production mechanism, synthesis and preparation, separation and purification, pharmacology None of them have been studied systematically and comprehensively. Some impurities have multiple tautomers. Due to the limitation of separation and purification technology, it is difficult to obtain monomeric impurities, which cannot be systematically studied, resulting in the quality of generic drugs being significantly worse than that of original drugs.

Method used

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  • Preparation method of erythromycin impurity D
  • Preparation method of erythromycin impurity D
  • Preparation method of erythromycin impurity D

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] The preparation method of erythromycin impurity D described in the present embodiment may further comprise the steps:

[0030] (1) Weigh 5 g of erythromycin, add 100 mL of water, slowly add concentrated hydrochloric acid dropwise under stirring at room temperature, keep the pH of the reaction solution at 1.0, stir and react for 0.5 h to obtain the reaction solution;

[0031] (2) Adjust the pH of the reaction solution to 8-9 with 1mol / L sodium hydroxide to obtain the reaction solution of erythromycin impurity D;

[0032] (3) Add methanol to dissolve the erythromycin impurity D reaction solution, separate on a 600mL C18 column, and elute with acetonitrile:water solution=40:60 (V / V), 50:50 (V / V), and 60:40 1.5 L, to obtain the fraction of the pure erythromycin impurity D, freeze-dried to obtain the pure erythromycin impurity D, with a purity of over 90% and a yield of 15.7%.

Embodiment 2

[0034] The preparation method of erythromycin impurity D described in the present embodiment may further comprise the steps:

[0035] (1) Weigh 5 g of erythromycin, add 125 mL of water, slowly add concentrated hydrochloric acid dropwise under stirring at room temperature, keep the pH of the reaction solution at 1.5, and stir for 0.7 h to obtain the reaction solution;

[0036] (2) Adjust the pH of the reaction solution to 8-9 with 1mol / L sodium hydroxide to obtain the reaction solution of erythromycin impurity D;

[0037] (3) Add methanol to dissolve the erythromycin impurity D reaction solution, separate it on a 600mL C18 column, use acetonitrile:water solution=40:60(V / V), 50:50(V / V), 60:40(V / V) V) 1.5 L of each was eluted to obtain the pure product of erythromycin impurity D, which was freeze-dried to obtain the pure product of erythromycin impurity D with a purity of over 90% and a yield of 12.6%.

Embodiment 3

[0039] The preparation method of erythromycin impurity D described in the present embodiment may further comprise the steps:

[0040] (1) Weigh 5 g of erythromycin, add 150 mL of water, slowly add concentrated hydrochloric acid dropwise under stirring at room temperature, keep the pH of the reaction solution at 2.0, and stir for 1 hour to obtain the reaction solution;

[0041] (2) Adjust the pH of the reaction solution to 8-9 with 0.5mol / L sodium hydroxide to obtain the reaction solution of erythromycin impurity D;

[0042] (3) Add methanol to dissolve the erythromycin impurity D reaction solution, separate it on a 600mL C18 column, use acetonitrile:water solution=40:60(V / V), 50:50(V / V), 60:40(V / V) V) 1.5 L of each was eluted to obtain the pure product of erythromycin impurity D, which was freeze-dried to obtain the pure product of erythromycin impurity D with a purity of over 90% and a yield of 11.3%.

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Abstract

The invention discloses a preparation method of an erythromycin impurity D. The preparation method comprises the following steps: adding water into erythromycin, carrying out stirring reaction at thetemperature of 25-30 DEG C and under acidic conditions, and carrying out separation and purification on the reaction solution to obtain the erythromycin impurity D. The preparation method of the erythromycin impurity D is mild in reaction condition, does not involve ultralow-temperature reaction, reduces process steps, and is suitable for pilot scale-up in laboratories. The purity of the preparederythromycin impurity D reaches 90% or above, the quality research requirement can be met, and meanwhile a technical basis is provided for improving the national quality standard of erythromycin.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a preparation method of erythromycin impurity D. Background technique [0002] Erythromycin (Erythromycin) belongs to the macrolide antibiotics, is a fermentation antibiotics, has been widely developed and applied in the medical field. The antibacterial spectrum is similar to that of penicillin, and it is effective against Gram-positive bacteria, such as Staphylococcus, Streptococcus pyogenes, Streptococcus viridans, Streptococcus pneumoniae, Streptococcus faecalis, Streptococcus hemolyticus, Clostridia, Bacillus diphtheriae, Bacillus anthracis, etc. Strong inhibitory effect. It also has a certain inhibitory effect on Gram-negative bacteria, such as Neisseria gonorrhoeae, Helicobacter, Bacillus pertussis, Brucella, Legionella, Neisseria meningitidis, Haemophilus influenzae, Bacteroides, some Shigella and Escherichia coli. In addition, it has inhibitory effect on m...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H17/08C07H1/00
CPCC07H17/08C07H1/00
Inventor 袁晓林顺权
Owner PI & PI BIOTECH