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A kind of preparation method and application of pteridine folic acid

A technology of pteridine folic acid and glutamic acid, applied in the field of preparation of pteridine folic acid, can solve the problems such as the production mechanism and control method of finished folic acid products that are not deeply studied, and achieve the effect of improving the quality control level of folic acid

Active Publication Date: 2019-04-26
ZHEJIANG SHENGDA BIO PHARM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these methods are only from the perspective of how to remove pteridine impurities, and have not studied in depth the production mechanism and control methods of other impurities in folic acid products such as pteridine folic acid

Method used

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  • A kind of preparation method and application of pteridine folic acid
  • A kind of preparation method and application of pteridine folic acid
  • A kind of preparation method and application of pteridine folic acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] (1) Synthesis of pteridine folic acid crude product

[0044] P-aminobenzoyl glutamic acid, triaminopyrimidine sulfate, trichloroacetone are dissolved in water, wherein based on mass ratio, p-aminobenzoyl glutamic acid: triaminopyrimidine sulfate: trichloroacetone: water = 1:2:3:100, control the pH of the reaction solution to 1, heat to 80°C, keep warm for 5 hours, cool down to 20°C, filter, adjust the pH of the filtrate to 5 with NaOH, and filter to obtain a crude product with a purity of 26.23%;

[0045] (2) Purification of pteridine folic acid

[0046] The crude product was dissolved with ammonia water, filtered, and the filtrate was put into semi-preparative chromatography, 10ml each time, the effluent was collected, combined, concentrated under reduced pressure, and the concentrated solution was diluted 2 times with purified water, then into semi-preparative chromatography, washed with 10% methanol by mass fraction out, collect the effluent, concentrate and freeze-...

Embodiment 2

[0052] (1) Synthesis of pteridine folic acid crude product

[0053] P-aminobenzoyl glutamic acid, triaminopyrimidine sulfate, trichloroacetone are dissolved in water, wherein based on mass ratio, p-aminobenzoyl glutamic acid: triaminopyrimidine sulfate: trichloroacetone: water = 1:3:4:120, control the pH of the reaction solution to 2, heat to 90°C, keep warm for 8 hours, cool down to 30°C, filter, adjust the pH of the filtrate to 3 with NaOH, and filter to obtain a crude product with a purity of 22.51%;

[0054] (2) Purification of pteridine folic acid

[0055] The crude product was dissolved with ammonia water, filtered, and the filtrate was put into semi-preparative chromatography, 10ml each time, the effluent was collected, combined, concentrated under reduced pressure, and the concentrated solution was diluted 2 times with purified water, then into semi-preparative chromatography, washed with 10% methanol by mass fraction out, collect the effluent, concentrate and freeze-...

Embodiment 3

[0058] (1) Synthesis of pteridine folic acid crude product

[0059] P-aminobenzoyl glutamic acid, triaminopyrimidine sulfate, trichloroacetone are dissolved in water, wherein based on mass ratio, p-aminobenzoyl glutamic acid: triaminopyrimidine sulfate: trichloroacetone: water = 1:3:5:150, control the pH of the reaction solution to 2.5, heat to 93°C, keep warm for 9 hours, cool down to 35°C, filter, adjust the pH of the filtrate to 4 with NaOH, and filter to obtain a crude product with a purity of 18.47%;

[0060] (2) Purification of pteridine folic acid

[0061] The crude product was dissolved with ammonia water, filtered, and the filtrate was put into semi-preparative chromatography, 10ml each time, the effluent was collected, combined, concentrated under reduced pressure, and the concentrated solution was diluted 4 times with purified water, then into semi-preparative chromatography, washed with 20% methanol by mass fraction out, collect the effluent, concentrate and freez...

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Abstract

The present invention relates to a method for preparing pteridine folic acid and its application. Using p-aminobenzoyl glutamic acid, triaminopyrimidine sulfate and trichloroacetone as raw materials, the chemical synthesis method can significantly increase the pteridine folic acid crude product. content, and then separated by preparative chromatography to obtain pteridine folic acid with a purity greater than 95%. The research of the invention is conducive to further research on the production mechanism and control method of pteridine folic acid, and can effectively improve the quality control level of folic acid.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and in particular relates to a preparation method of pteridine folic acid and its application in folic acid quality control. Background technique [0002] 6-pterinylfolic acid [0003] [0004] English name: N,N-bis-[4-[(2-amido-4-oxo-1,4-dihydro-6-terene)methylamino]]benzoyl-L-glutamic acid [0005] Chinese name: N,N-di-(4-((2-amino-4-hydroxy-6-pteridinyl)methylamino))benzoyl-L-glutamic acid [0006] Pteridine folic acid, that is, EP pharmacopoeia folic acid impurity E. [0007] Folic acid, also known as vitamin B9, is a water-soluble vitamin that was extracted and purified by Mitchell (H.K. Mitchell, 1941) from spinach leaves, hence the name folic acid. It can promote the maturation of immature cells in the bone marrow. If humans lack folic acid, it can cause megaloblastic anemia and leukopenia, which is especially important for pregnant women. [0008] Insufficient intake of folic acid ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D519/00G01N1/28
CPCC07D519/00G01N1/28
Inventor 庞正查张仲景王程鹏许文韬陈优富陈敏陈蒙刘露
Owner ZHEJIANG SHENGDA BIO PHARM