Method for preparing high-content creatine phosphate disodium salt

A creatine phosphate disodium salt, high-content technology, applied in chemical instruments and methods, compounds of periodic table Group 5/15 elements, organic chemistry, etc., can solve the problem that creatine phosphate disodium salt cannot effectively increase the content , high production costs, difficult industrial production and other problems, to avoid waste of human and material resources, improve safety and effectiveness, and reduce production costs

Active Publication Date: 2012-10-03
SHANGHAI LONGXIANG BIO MEDICINE DEV CO LTD
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Problems solved by technology

But because phosphocreatine disodium salt itself has very strong polarity, the very strong inorganic sodium salt and inorganic phosphate produced in the reaction will also be brought in during the refining process, so it is still very difficult to produce in its preparation even through repeated refining. It is difficult to obtain the final product creatine phosphate disodium salt with a high content of 99%, such as US3632603, CN101492470A
Simple repeated refining of the final product creatine phosphate disodium salt cannot effectively increase its content, which is also the bottleneck where the drug has not been able to obtain high content at the industrial level
In addition, it has been reported that dibenzyl phosphite is used to prepare creatinine phosphate intermediates, such as US3036087A, CN101274943A, but this method has a total of four steps of reaction, and finally needs to use precious metal palladium carbon hydrogenation to remove benzyl group, its operability is not strong, production High cost, difficult to industrial production

Method used

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preparation example Construction

[0016] The invention provides a method for preparing high-content creatine phosphate disodium salt, comprising the following steps:

[0017] 1. Preparation of Crude Creatinine Phosphoryl Chloride

[0018] Creatinine and phosphorus oxychloride are used as starting materials for condensation. After the reaction is completed, most of the phosphorus oxychloride (recyclable) is evaporated under reduced pressure. Body rough.

[0019] Wherein, the mass ratio of creatinine to phosphorus oxychloride is 1:30-90.

[0020] 2. Refined creatinine phosphoryl chloride

[0021] The obtained crude creatinine phosphorus oxychloride was dissolved in solvent A at room temperature, stirred at room temperature for 2 hours, and suction filtered to remove insoluble matter. The solvent B was slowly added dropwise to the above solution in an ice bath with continuous stirring, and crystals were gradually precipitated. Suction filtration, rinse with solvent B, and dry under reduced pressure at 45°C to...

Embodiment 1

[0029] 1: Preparation of Crude Creatinine Phosphoryl Chloride

[0030] At room temperature, put 10 g of creatinine into a 500 ml three-neck flask, then add 450 g of phosphorus oxychloride, and heat to reflux in an oil bath at 105° C. for 30 minutes. Then immediately lower the temperature to 30±5°C, and distill off most of the phosphorus oxychloride (about 400g) under reduced pressure. Cool to room temperature, add 20ml of toluene, control the temperature to 0-5°C for crystallization, and obtain a viscous product which is crude creatinine phosphorus oxychloride.

[0031] 2: Refining of creatinine phosphoryl chloride

[0032] The crude product of creatinine phosphorus oxychloride was rapidly dissolved in 100ml of dichloromethane, stirred for 2 hours, and viscous insoluble matter was precipitated. Suction filtration to remove insoluble matter. Add 200ml of n-hexane dropwise to the filtrate under temperature control at 0±5°C, gradually precipitate white crystals, rinse with n-h...

Embodiment 2

[0036] 1: Preparation of Crude Creatinine Phosphoryl Chloride

[0037] At room temperature, put 100g of creatinine into a 5000ml three-necked flask, then add 3000g of phosphorus oxychloride, and heat to reflux in an oil bath at 105°C for 30 minutes. Then immediately lower the temperature to 30±5°C, and distill most of the phosphorus oxychloride (about 2700g) under reduced pressure. Cool to room temperature, add 200ml of toluene, control the temperature to 0-5°C for crystallization, and obtain a viscous product which is crude creatinine phosphorus oxychloride.

[0038] 2: Refining of creatinine phosphoryl chloride

[0039] The crude product of creatinine phosphorus oxychloride was quickly dissolved in 1000ml of dichloromethane, stirred for 2 hours, and viscous insoluble matter was precipitated. Suction filtration to remove insoluble matter. Add 2000ml of n-heptane dropwise to the filtrate under temperature control at 0±5°C, gradually precipitate white crystals, rinse with n-...

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Abstract

The invention discloses a method for preparing high-content creatine phosphate disodium salt, comprising the steps as follows: (1) conducting a condensation reaction on creatinine and phosphorus oxytrichloride to obtain crude creatinine phosphorus oxychloride; (2) dissolving the crude creatinine phosphorus oxychloride in a solvent A, then stirring and filtering, adding a solvent B to the filtrate to separate out the crystal and obtain fine creatinine phosphorus oxychloride; (3) hydrolyzing fine creatinine phosphorus oxychloride in sodium hydroxide aqueous solution to obtain the high-content creatine phosphate disodium salt, wherein the solvent A is halohydrocarbon and the solvent B is aliphatic hydrocarbon.

Description

technical field [0001] The invention relates to a preparation method of high-content creatine phosphate disodium salt. Background technique [0002] Creatine phosphate disodium salt, as a cardioprotective drug, has been widely used in the prevention and treatment of various heart diseases. It has high curative effect and low side effects, and its medical value ranks first among similar drugs. At present, the preparation methods of creatine phosphate disodium salt include synthetic method, biological extraction method and enzymatic method. In the synthesis of creatine phosphate disodium salt without a specific stereostructure, the macromolecular kinase does not reflect its advantages of chiral synthesis or chiral induction, and the reaction yield is low, and the overall production cost is high. The biological extraction method mainly uses animal muscle tissue as raw material, but the relative content of creatine phosphate in muscle tissue is relatively low, and the process i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F9/22
Inventor 冯虓唐方强周志成陆洋琼景桂香计平
Owner SHANGHAI LONGXIANG BIO MEDICINE DEV CO LTD
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