A method for refining troxerutin

Abstract

The invention discloses a method for refining troxerutin, belongs to the technical field of chemical pharmacy, and mainly solves the problems of low purity and complicated operation of troxerutin in the prior art, comprising the following steps: (1) troxerutin is placed in a beaker, phenylboric acid is added, heated for reaction, filtered and washed to obtain an intermediate; (2) methanol is added to the intermediate, pH is adjusted, crystallization is filtered, and washing and drying are performed. The invention provides a method for refining troxerutin, which solves the problems of low purity and complicated operation of troxerutin, wherein phenylboric acid is added to generate an intermediate through complexation reaction, and some impurities that cannot undergo complexation reaction are removed, and the intermediate is subjected to acid hydrolysis in hot methanol to obtain troxerutin, and the troxerutin is obtained by cooling, crystallization, recrystallization and purification, and the operation is simple, and the purity of the refined troxerutin is ≥97.5%.

Description

Technical Field

[0001] The invention relates to the technical field of chemical pharmacy, and more specifically to a method for refining troxerutin. Background Art

[0002] Troxerutin is also known as vitamin P4, hydroxyethyl rutin, vinorutin, toxerutin, etc. Its chemical formula is C 33 H 42 O 19 It can be used as an anticoagulant and has the effect of preventing thrombosis. It is suitable for hemiplegia, aphasia, myocardial infarction, arteriosclerosis, etc. caused by cerebral thrombosis and cerebral embolism.

[0003] This product is a semi-synthetic flavonoid compound made from rutin by hydroxyethylation. It has the function of inhibiting the aggregation of red blood cells and platelets, preventing thrombosis, and at the same time increasing the oxygen content in the blood, improving microcirculation, and promoting the formation of new blood vessels to enhance collateral circulation. It has a protective effect on endothelial cells, can resist vascular damage caused by 5-hydroxytryptamine and bradykinin, increase the resistance of capillaries, reduce the permeability of capillaries, and prevent edema caused by increased vascular permeability. It also has the functions of resisting radiation damage, inflammation, allergy and ulcer.

[0004] The purification methods of troxerutin include alcohol solvent recrystallization and ion exchange resin. Among them, the alcohol solvent recrystallization process method has a higher yield, but its purity is not high, mainly because a large amount of sodium chloride is produced by the reaction of sodium hydroxide and chloroethanol. The generated impurities are similar to the chemical structure of troxerutin, have similar properties, and are difficult to remove; and the ethylene chloride method uses rutin and ethylene chloride as raw materials, reacts in an alcohol solution, and adds an alkaline catalyst to cause a substitution reaction. However, a strong base is used as a catalyst, and side reactions such as hydrolysis and oxidation are prone to occur in the later stage, which increases the difficulty of purification, has a low yield and a high industrial cost. Therefore, it is necessary to provide a purification method for troxerutin to solve the problems of low purity and complicated operation. Summary of the invention

[0005] The purpose of the present invention is to provide a method for refining troxerutin. The method solves the problems of low purity and complicated operation of troxerutin, wherein phenylboric acid is added to generate an intermediate for complex reaction, and some impurities that cannot undergo complex reaction are removed. The intermediate is subjected to acid hydrolysis in hot methanol to obtain troxerutin, and the troxerutin is purified by cooling, crystallization, recrystallization, and purification, and the purity is ≥97.5%.

[0006] The technical solution of the present invention is: a method for refining troxerutin, comprising the following steps:

[0007] (1) Troxerutin is placed in a beaker, phenylboric acid is added, heated for reaction, filtered and washed to obtain an intermediate;

[0008] (2) Add methanol to the intermediate, heat it, adjust the pH, crystallize, filter, wash and dry.

[0009] Preferably, in g / mL, the mass volume ratio of the troxerutin and the methanol solution is 1:4-8, and the weight ratio of phenylboric acid to troxerutin is 0.2-0.4:1.

[0010] Preferably, the heating temperature is 40-60° C. and the reaction time is 1-4 h.

[0011] Preferably, in step (1), the washing is methanol washing.

[0012] Preferably, the mass volume ratio of the intermediate to the methanol solution is 1:8-20 in g / mL.

[0013] Preferably, hydrochloric acid is used to adjust the solution pH to 2-4.

[0014] Preferably, the crystallization temperature is 10-30°C and the crystallization time is 3-8h.

[0015] Preferably, in step (2), the washing is methanol washing.

[0016] Beneficial Effects

[0017] 1. The present invention provides a method for refining troxerutin, wherein an intermediate is generated by complexing troxerutin with phenylboric acid, and some impurities that cannot undergo complexing reaction are removed. The intermediate is hydrolyzed by acid in hot methanol to obtain troxerutin, thereby improving the purity of troxerutin.

[0018] 2. The invention provides a method for refining troxerutin, wherein troxerutin and phenylboric acid react to form an intermediate by using methanol as a solvent, and then the intermediate is filtered and washed with methanol, and then heated in methanol, hydrochloric acid is added to adjust the pH, crystallized and filtered, and then washed and dried. The process for refining troxerutin is simple to operate and has high purity. DETAILED DESCRIPTION

[0019] The present invention will be further described below in conjunction with specific embodiments.

[0020] Example 1

[0021] 50g of troxerutin was placed in a flask, 200ml of methanol and 10g of phenylboric acid were added, and the mixture was heated to 40°C with stirring, reacted for 1h, cooled to room temperature, filtered, and washed with methanol. The solid was placed in 400ml of methanol, heated to 40°C, adjusted to a solution pH of 2 with hydrochloric acid, cooled to 10°C for crystallization for 3h, filtered, washed with methanol, and dried to obtain 45g of troxerutin finished product with a purity of 97.5%.

[0022] Example 2

[0023] 50g of troxerutin was placed in a flask, 300ml of methanol and 15g of phenylboric acid were added, and the mixture was stirred and heated to 50°C for 2h. After cooling to room temperature, the mixture was filtered and washed with methanol. The solid was placed in 600ml of methanol, heated to 50°C, and the solution pH was adjusted to 3 with hydrochloric acid. The solid was cooled to 20°C for crystallization for 5h, filtered, washed with methanol, and dried to obtain 45g of troxerutin finished product with a purity of 97.8%.

[0024] Example 3

[0025] 50g of troxerutin was placed in a flask, 400ml of methanol and 20g of phenylboric acid were added, and the mixture was stirred and heated to 60°C for 4h. After cooling to room temperature, the mixture was filtered and washed with methanol. The solid was placed in 800ml of methanol, heated to 60°C, and the solution pH was adjusted to 4 with hydrochloric acid, and the temperature was lowered to 30°C for crystallization for 8h, filtered, washed with methanol, and dried to obtain 46g of troxerutin finished product with a purity of 97.6%.

[0026] The above are only preferred embodiments of the present invention. It should be pointed out that for those skilled in the art, several modifications and improvements can be made without departing from the structure of the present invention, which will not affect the effect and practicality of the implementation of the present invention.

Claims

1. A method for refining troxerutin, characterized in that, The method is as follows: (1) Troxerutin is placed in a beaker, methanol and phenylboric acid are added, heated for reaction, filtered and washed to obtain an intermediate; (2) adding methanol to the intermediate, heating, adjusting the pH, crystallizing, filtering, washing and drying; Wherein, in terms of g / mL, the mass volume ratio of the troxerutin and the methanol solution is 1:4-8, and the weight ratio of phenylboric acid to troxerutin is 0.2-0.4:1; in terms of g / mL, the mass volume ratio of the intermediate and the methanol solution is 1:8-20.

2. The method for refining troxerutin according to claim 1, wherein The heating temperature is 40-60°C and the reaction time is 1-4h.

3. The method for refining troxerutin according to claim 1, characterized in that In the step (1), the washing is methanol washing.

4. The method for refining troxerutin according to claim 1, characterized in that The solution pH was adjusted to 2-4 with hydrochloric acid.

5. The method for refining troxerutin according to claim 1, characterized in that The crystallization temperature is 10-30°C, and the crystallization time is 3-8h.

6. The method for refining troxerutin according to claim 1, characterized in that In the step (2), the washing is methanol washing.