Refining method of disodium phosphocreatine

A technology of creatine phosphate disodium salt and creatine phosphate disodium salt is applied in the refining field of creatine phosphate disodium salt, can solve the problems of poor timeliness, long crystallization time, long process time, etc., and can meet the requirements of industrialized large-scale production , the conditions are mild and easy to control, and the process method is simple.

Active Publication Date: 2014-05-07
重庆莱美隆宇药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These two methods are obtained and it is easier to obtain crystalline high-water-containing hexahydrate. Although this kind of crystal has medicinal prospects, its research is not yet mature.
[0005] As for the tetrahydrate of creatine phosphate disodium salt (i.e. creatine phosphate sodium), Chinese patent CN101812088A uses a preparation chromatographic column for separation and purification to obtain creatine phosphate sodium Refined products, this method uses chromatographic columns to refine, not only the cost is high, the process conditions are complicated, and it is not conducive to industrial production
Chinese patent CN101492470A uses high-volume ethanol for repeated recrystallization. This method takes a long time to crystallize and uses a large amount, and needs to be repeated many times. Not only is the cost high, but the timeliness is poor
Chinese patent CN101486730A directly adds water-containing ethanol and crystallizes after standing still for a long time. This process takes a long time, the product quality is not high, and the yield is low, which is not conducive to large-scale production.
However, the yield of methanol refining crystallization is very low, and the scale of ultrasonic crystallization of ethanol is small, which are not conducive to industrial production.
[0007] None of the above methods can obtain high-quality and high-yield creatine phosphate sodium under low-cost conditions, and the timeliness is not good, and some links are difficult to control, and Leading to unstable product quality, it is difficult to achieve large-scale production

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

[0030] Take 15.0 g of crude creatine phosphate disodium (purity 92.1%), add 15 ml of water at room temperature and stir for 10 minutes to dissolve, filter, and add 45 ml of ethanol to the filtrate with stirring to precipitate a large amount of oil; let it stand for 1 hour and separate Remove the supernatant liquid, add 30ml methanol to the oily substance with stirring, a large amount of crystals will be precipitated, be slurried and crystallized for 1 hour, and then filtered; the filter cake is transferred to the reaction flask, 30ml ethanol is added and washed for 1 hour, filtered, the filter cake is at 40 After drying under reduced pressure at ~45°C, 13.0 g of creatine phosphate disodium salt tetrahydrate compound was obtained, with a purity of 99.1% and a yield of 86.7%.

example 2

[0032] Take 15.0 g of creatine disodium phosphate (purity 88.5%), add 75ml of water at room temperature and stir for 10 minutes to dissolve, filter, add 225ml of ethanol to the filtrate with stirring, and precipitate a large amount of oil; let it stand for 1 hour and separate Remove the supernatant liquid, add 75ml of methanol to the oily substance under stirring to precipitate a large number of crystals, beating and crystallizing for 1 hour, filter; transfer the filter cake to the reaction flask, add 75ml of ethanol, stir and wash for 1 hour, filter, filter the cake at 40~ After drying under reduced pressure at 45°C, 10.5 g of creatine phosphate disodium salt tetrahydrate compound was obtained, with a purity of 99.2% and a yield of 70.0%.

example 3

[0034] Take 15.0 grams of crude creatine phosphate disodium (purity 92.1%), add 15ml of water at room temperature and stir for 10 minutes to dissolve, filter, and add 45ml of isopropanol to the filtrate with stirring to precipitate a large amount of oil; let it stand for 1 hour Afterwards, the supernatant liquid was separated and removed. Under stirring, 30ml of methanol was added dropwise to the oily substance to precipitate a large number of crystals, which were slurried for 1 hour and filtered; the filter cake was transferred to the reaction flask, and 30ml of isopropanol was added and washed for 1 hour, filtered, filtered After the cake was dried under reduced pressure at 40-45°C, 13.5 g of creatine phosphate disodium salt tetrahydrate compound was obtained, with a purity of 99.0% and a yield of 90.0%.

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Abstract

The invention discloses a refining method of disodium phosphocreatine. The method comprises steps that: a sodium phosphocreatine crude product is dissolved in water, the solution is filtered, and a micro-molecular solvent is dropped into the filtrate while stirring, such that a large amount of oily matters are precipitated; the oily matters are settled and precipitated, a supernatant is removed, methanol is dropped into the oily matters while stirring, a large amount of crystals are precipitated, and the crystals are beaten and filtered; the filter cake is transferred into a reaction bottle, washed by using a micro-molecular solvent while stirring, and is filtered; the filter cake is dried with reduced pressure at a temperature of 40 to 45 DEG C, such that disodium phosphocreatine tetrahydrate with a high quality is obtained. The refining method provided by the invention has advantages of mild technical condition, simple and easy-to-control method, high yield, and stable product quality. The method satisfies the requirement of large-scale productions, and brings in good social and economic benefits.

Description

technical field [0001] The invention relates to a method for refining creatine phosphate disodium salt, in particular to a method for refining creatine phosphate disodium salt tetrahydrate. Background technique [0002] Creatine phosphate disodium salt (also known as creatine phosphate sodium salt) is an important derivative of creatine and a high-energy storage substance in the human body. Its tetrahydrate (that is, creatine phosphate sodium) has been widely used as One of the prevention and treatment medicines for various heart diseases, in addition to being taken directly as a nutritional product, it can also be widely used in clinical diagnosis as a biochemical agent. At present, the forms of creatine phosphate disodium salt recognized by researchers include creatine phosphate disodium salt hexahydrate and creatine phosphate disodium salt tetrahydrate, and now the tetrahydrate can be directly used in pharmaceuticals , and the relevant pharmaceutical and clinical researc...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07F9/22
Inventor 李小林
Owner 重庆莱美隆宇药业有限公司
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