Hydrolysis crude extraction method of galanthamine

Abstract

The invention provides a galanthamine hydrolysis crude extraction method. The method comprises the following steps: drying plant raw materials, and crushing the dried plant raw materials to 20-40 meshes; pouring a solvent and the crushed plant raw materials into a hydrolysis tank according to a weight ratio of 1: (10-15); heating and refluxing the stock solution; filtering the refluxed stock solution, and separating residues from hydrolysate; adding a regulator into the hydrolysate, and filtering to form a crude product liquid; adding an extraction liquid to extract the crude product liquid to obtain a purified crude product; concentrating the purified crude product by 5 times, and performing spray drying to obtain a galanthamine crude extract. According to the scheme, the hydrolysis efficiency and the component stability are balanced by optimizing the acid concentration, the temperature and the time. Dichloromethane or ethyl acetate is adopted to improve the extraction efficiency and safety, and finally, the extraction process is monitored through an external TLC or HPLC system by recovering a solvent and reducing waste liquid discharge, so that the purpose of rapid extraction is achieved.

Description

Technical Field

[0001] The present invention relates to the technical field of galantamine extraction, and in particular to a hydrolysis and crude extraction method of galantamine. Background Art

[0002] With the increase in the global elderly population, the disease burden caused by Alzheimer's disease is increasing day by day. As a central cholinesterase inhibitor with mild effects and minor adverse reactions, galantamine has been re - emphasized.

[0003] At present, there are various methods to obtain galantamine. Lycoris radiata contains about 0.1‰ of galantamine. Then hydrobromic acid is added to synthesize galantamine hydrobromide, and finally anhydrous ethanol is used for recrystallization to obtain high - quality galantamine hydrobromide. Therefore, separating galantamine from plant materials is still an effective alternative way for its large - scale production.

[0004] The extract is used to treat senile dementia, myasthenia gravis, progressive muscular dystrophy, sequelae of poliomyelitis, childhood cerebral palsy, sensory or motor disorders caused by nervous system diseases, polyneuritis, etc. However, the traditional extraction methods are complex in operation and high in cost. Summary of the Invention

[0005] The purpose of the present invention is to provide a hydrolysis and crude extraction method of galantamine with reasonable process and good extraction effect.

[0006] To achieve the above purpose, the technical solution provided by the present invention is: a hydrolysis and crude extraction method of galantamine, The first step: drying the plant raw material and then crushing it to 20 - 40 mesh; The second step: pouring the solvent and the crushed plant raw material into the hydrolysis tank according to a weight ratio of 1:10 - 15; The third step: heating the stock solution, refluxing, and hydrolyzing the glycosidic bond to release free alkaloids; The fourth step: filtering the stock solution after refluxing, separating the residue and the hydrolysis solution, and repeating the second step and the third step for extracting the residue; The fifth step: adding a regulator to the hydrolysis solution, adjusting the pH of the filtrate to 9 - 10, and filtering through a filter tank to form a crude product solution; The sixth step: adding an extraction solution to extract the crude product solution, with the extraction times being 1 - 4 times to obtain a purified crude product; The seventh step: concentrating the purified crude product by 5 times, and obtaining a paste - like or powdery galantamine crude extract after spray drying.

[0007] In the first step, the bulb or the above - ground part of the Amaryllidaceae plant is dried and crushed to 20 - 40 mesh to increase the surface area to improve the extraction efficiency; when the lipid content in the raw material is too high, it is defatted with petroleum ether or n - hexane.

[0008] The solvent in the second step is a 0.5%-2% dilute hydrochloric acid or sulfuric acid solution.

[0009] The third step is to reflux for 2-4 hours at 80-90 °C to hydrolyze the glycosidic bond and release the free alkaloid.

[0010] The regulator in the fourth step is ammonia water or NaOH, which adjusts the pH of the filtrate to 9-10 to free the alkaloid and reduce its water solubility.

[0011] The extraction liquid in the sixth step is extracted multiple times with an organic solvent such as chloroform, dichloromethane or ethyl acetate, and the organic phases are combined.

[0012] After adopting the above scheme, the present invention balances the hydrolysis efficiency and component stability by optimizing the acid concentration, temperature and time. Dichloromethane or ethyl acetate is used to improve the extraction efficiency and safety. Finally, by recovering the solvent, the waste liquid discharge is reduced, and the extraction process is monitored by an external TLC or HPLC system, so as to achieve the purpose of rapid extraction. Description of the Drawings

[0013] Figure 1 It is the process schematic diagram of the present invention. Detailed Embodiments

[0014] The following further describes the present invention in conjunction with all the drawings. The preferred embodiment of the present invention is as follows: Refer to the attached Figure 1 , a galanthamine hydrolysis and crude extraction method described in this embodiment: First step: Dry and crush the bulbs or aerial parts of the Amaryllidaceae plants to 20-40 meshes to increase the surface area and improve the extraction efficiency; when the lipid content in the raw material is too high, degrease with petroleum ether or n-hexane; Second step: Pour the solvent and the crushed plant raw material into the hydrolysis tank at a weight ratio of 1:10-15; the solvent is a 0.5%-2% dilute hydrochloric acid or sulfuric acid solution; the solid-liquid ratio is 1:10~1:15 (raw material: solvent); Third step: Heat up the stock solution and reflux to hydrolyze the glycosidic bond and release the free alkaloid; the above is to reflux for 2-4 hours at 80-90 °C to hydrolyze the glycosidic bond and release the free alkaloid; the purpose is to destroy the cell structure and convert the bound galanthamine into the free form.

[0015] Fourth step: Filter the stock solution after refluxing to separate the residue and the hydrolysis solution, and repeat the second step and the third step for the residue for extraction; filter while it is hot to separate the residue and the hydrolysis solution, and the residue can be repeatedly extracted to improve the yield; Fifth step: Add the regulator to the hydrolysis solution, adjust the pH of the filtrate to 9-10, and filter through the filter tank to form a crude product solution; the regulator is ammonia water or NaOH, which adjusts the pH of the filtrate to 9-10 to free the alkaloid and reduce its water solubility; Sixth step: Add the extraction solution to extract the crude product solution. The number of extraction times is 1 - 4 times to obtain the purified crude product. The extraction solution is obtained by extracting with organic solvents such as chloroform, dichloromethane or ethyl acetate for multiple times, and combining the organic phases. After cooling, adjust the pH to neutral (neutralized with NaOH) to avoid the degradation of alkaloids in strong acid for a long time. Seventh step: Concentrate the purified crude product by 5 times, and obtain the crude extract of galanthamine in paste or powder form after spray drying; or wash the precipitate with distilled water until neutral, and dry it under vacuum at 40 - 50 °C to obtain the crude product of galanthamine. Eighth step: Dissolve the crude product of galanthamine with dilute acid (such as 1% HCl), and filter to remove insoluble substances. Ninth step: Dissolve the crude product in an ethanol - water mixed solvent, and conduct preliminary purification by low - temperature crystallization.

[0016] When the above process is used, avoid long - term high temperature or extreme pH during extraction to prevent the degradation of galanthamine, thereby increasing the extraction stability. Protective equipment should be worn during the operation of acids, alkalis and organic solvents, and good ventilation should be ensured. The crude extract can be further purified by silica gel column chromatography (eluent: chloroform - methanol gradient), crystallization (ethanol - water system) or HPLC. At the same time, degrease with petroleum ether or n - hexane to remove non - polar impurities. This solution optimizes the acid concentration, temperature and time to balance the hydrolysis efficiency and component stability. Use dichloromethane or ethyl acetate to improve the extraction efficiency and safety. Finally, reduce the waste liquid discharge by recycling the solvent, and monitor the extraction process through an external TLC or HPLC system to achieve the purpose of rapid extraction.

[0017] The above - mentioned embodiments are only the preferred embodiments of the present invention, and do not limit the scope of implementation of the present invention. Therefore, all changes made according to the shape and principle of the present invention should be covered within the protection scope of the present invention.

Claims

1. A method for the crude extraction of galanthamine by hydrolysis, characterized in that: The first step: drying the plant raw materials and then pulverizing them to 20-40 mesh; The second step: pouring the solvent and the pulverized plant raw materials into the hydrolysis tank according to a weight ratio of 1:10-15; The third step: heating the stock solution, refluxing, and hydrolyzing the glycosidic bond to release free alkaloids; The fourth step: filtering the stock solution after refluxing, separating the residue and the hydrolyzate, and repeating the second step and the third step for the residue extraction; The fifth step: adding a regulator to the hydrolyzate, adjusting the pH of the filtrate to 9-10, and filtering through a filter tank to form a crude product solution; The sixth step: adding an extraction solution to extract the crude product solution, with the extraction times being 1-4 times to obtain a purified crude product; The seventh step: concentrating the purified crude product by 5 times and spray-drying to obtain a paste-like or powdered crude extract of galanthamine.

2. The galanthamine hydrolysis crude extraction method according to claim 1, characterized in that: In the first step, the bulbs or aerial parts of plants of the Amaryllidaceae family are dried and then pulverized to 20-40 mesh to increase the surface area and improve the extraction efficiency; when the lipid content in the raw materials is too high, they are defatted with petroleum ether or n-hexane.

3. A galanthamine hydrolysis crude extraction method according to claim 1, characterized in that: The solvent in the second step is a 0.5%-2% dilute hydrochloric acid or sulfuric acid solution.

4. A galanthamine hydrolysis crude extraction method according to claim 1, characterized in that: In the third step, refluxing is carried out at 80-90 °C for 2-4 hours to hydrolyze the glycosidic bond and release free alkaloids.

5. A galanthamine hydrolysis crude extraction method according to claim 1, characterized in that: The regulator in the fifth step is ammonia water or NaOH, adjusting the pH of the filtrate to 9-10 to free the alkaloids and reduce their water solubility.

6. A galanthamine hydrolysis crude extraction method according to claim 1, characterized in that: The extraction solution in the sixth step is to use an organic solvent such as dichloromethane or ethyl acetate for multiple extractions and combine the organic phases.

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