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Preparation method of amoxicillin impurity E

An amoxicillin and impurity technology, applied in the field of medicinal chemistry, can solve the problems of affecting drug safety, difficult to obtain monomer impurities, carcinogenic teratogenicity of impurities, etc., to meet the needs of quality research, high purity and yield, and reaction conditions. mild effect

Pending Publication Date: 2020-04-17
PI & PI BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] Amoxicillin impurities are a class of ingredients that have no 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 generic amoxicillin in China is various, resulting in different impurities. Different from the process of the original drug, the content and type of impurities will also be different. However, the domestic production mechanism, synthesis preparation, Separation, purification, and pharmacology have not been systematically and comprehensively studied. Some impurities have multiple tautomers. Due to the limitation of separation and purification technology, it is difficult to obtain monomeric impurities and cannot be systematically studied. As a result, the quality of generic drugs is significantly worse than that of original research. medicine

Method used

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  • Preparation method of amoxicillin impurity E
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  • Preparation method of amoxicillin impurity E

Examples

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Effect test

Embodiment 1

[0036] A kind of embodiment of the preparation method of amoxicillin impurity E of the present invention, the preparation method of amoxicillin impurity E described in this embodiment is:

[0037] (1) Weigh 5g of amoxicillin, add 100mL of 0.5mol / L hydrochloric acid solution to the amoxicillin, heat and react at 50°C for 1h;

[0038] (2) adopting 1mol / L sodium hydroxide solution to adjust the pH value of the product obtained in step (1) to a pH value of 3.0 to obtain the amoxicillin impurity E reaction solution;

[0039] (3) Separation for the first time: Mix potassium dihydrogen phosphate aqueous solution and acetonitrile according to different volume ratios to obtain a plurality of mixed solutions; The second mixed solution taken off and the third mixed solution used for eluting for the third time; in the first mixed solution, the volume percentage of potassium dihydrogen phosphate aqueous solution is 97%, and the volume percentage of acetonitrile is 3%; the described In the...

Embodiment 2

[0042] A kind of embodiment of the preparation method of amoxicillin impurity E of the present invention, the preparation method of amoxicillin impurity E described in this embodiment is:

[0043] (1) Weigh 5g of amoxicillin, add 250mL of 0.3mol / L hydrochloric acid solution to the amoxicillin, and heat at 75°C for 1.5h;

[0044] (2) adopting 1mol / L sodium hydroxide solution to adjust the pH value of the product obtained in step (1) to a pH value of 4.0 to obtain the amoxicillin impurity E reaction solution;

[0045] (3) Separation for the first time: Mix potassium dihydrogen phosphate aqueous solution and acetonitrile according to different volume ratios to obtain a plurality of mixed solutions; The second mixed solution taken off and the third mixed solution used for eluting for the third time; in the first mixed solution, the volume percentage of potassium dihydrogen phosphate aqueous solution is 96%, and the volume percentage of acetonitrile is 4%; the described In the sec...

Embodiment 3

[0048] A kind of embodiment of the preparation method of amoxicillin impurity E of the present invention, the preparation method of amoxicillin impurity E described in this embodiment is:

[0049] (1) Weigh 5g of amoxicillin, add 500mL of 0.1mol / L hydrochloric acid solution to the amoxicillin, heat and react at 90°C for 2h;

[0050] (2) adopting 1mol / L sodium hydroxide solution to adjust the pH value of the product obtained in step (1) to a pH value of 5.0 to obtain the amoxicillin impurity E reaction solution;

[0051] (3) Separation for the first time: Mix potassium dihydrogen phosphate aqueous solution and acetonitrile according to different volume ratios to obtain a plurality of mixed solutions; The second mixed solution taken off and the third mixed solution used for eluting for the third time; in the first mixed solution, the volume percentage of potassium dihydrogen phosphate aqueous solution is 98%, and the volume percentage of acetonitrile is 2%; the described In the...

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Abstract

The invention relates to a preparation method of an amoxicillin impurity E. The preparation method comprises the following steps: (1) adding an acid solution into amoxicillin, heating and reacting; (2) adjusting a pH value of the product obtained in the step (1) to 3-5 to obtain an amoxicillin impurity E reaction solution; (3) primary separation: mixing a potassium dihydrogen phosphate aqueous solution and acetonitrile according to different volume ratios to obtain a plurality of mixed solutions; sequentially eluting the amoxicillin impurity E reaction solution obtained in the step (2) by taking a C18 column as a separation column and taking a plurality of mixed solutions as eluents to obtain an amoxicillin impurity E crude product; and (4) secondary separation: diluting the amoxicillin impurity E crude product obtained in the step (3), then taking the C18 column as the separation column, sequentially adopting acetonitrile aqueous solutions with different concentrations as eluents to separate the diluted product, and drying the eluents to obtain the amoxicillin impurity E. The preparation method is simple and convenient, and reaction conditions are mild.

Description

technical field [0001] The invention relates to a preparation method of amoxicillin impurity E, which belongs to the technical field of medicinal chemistry. Background technique [0002] Amoxicillin belongs to β-lactam antibiotics, is a semi-synthetic acid-resistant broad-spectrum penicillin antibiotics, and has been widely developed and applied in the medical field. Amoxicillin has strong bactericidal effect and strong ability to penetrate cell walls. It is one of the most widely used oral penicillins at present. Its preparations include capsules, tablets, granules, dispersible tablets and so on. It can be used for upper respiratory tract infections such as otitis media, sinusitis and tonsillitis caused by hemolytic Streptococcus, Streptococcus pneumoniae, Staphylococcus or Haemophilus influenzae. [0003] Amoxicillin impurities are a class of ingredients that do not have any medicinal effect in medicines, and some impurities are carcinogenic and teratogenic. These impurit...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D277/06
CPCC07D277/06C07B2200/07
Inventor 袁晓林顺权
Owner PI & PI BIOTECH
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