CN101838273B - Method for Extracting Strychnine from Nuxychnium - Google Patents

Abstract

The invention discloses a method for extracting strychnine from the traditional Chinese medicine Nuxychnium, which comprises the following steps: (1) Nuxychnium coarse powder is extracted with water reflux, and the extract is concentrated; (2) The concentrated solution is added with a polymer flocculant for adsorption Clarification; (3) add alkali to the clarified liquid to adjust the alkalinity, and collect the precipitate A; (4) dissolve the precipitate A with dilute sulfuric acid, filter off the insoluble matter, adjust the filtrate to alkalinity and precipitate the precipitate B; (5) dissolve the precipitate B with dilute hydrochloric acid, crystallize, Obtain coarse crystallization of strychnine hydrochloride; (6) recrystallization of strychnine hydrochloride. Compared with the traditional strychnine preparation technology, the method has the advantages of little environmental pollution, low production cost and high product purity.

Description

Method for Extracting Strychnine from Nuxychnium

technical field

The invention relates to a method for extracting strychnine from Nuxychnium.

Background technique

Nuxychia is bitter in nature and flavor, cold, has great poison, returns to liver, spleen meridian, has the effect of dispelling stagnation, reducing swelling, dredging collaterals and relieving pain, and is used for bruises, swelling and pain, rheumatic paralysis, rheumatoid arthralgia, numbness and paralysis and other diseases. Nuxychnium main active ingredients are indole alkaloids, the total alkaloid content is about 3%-5%, of which strychnine (strychnine) and strychnine (brucine) account for about 80%. Hypoxine, strychnine, pseudo strychnine, pseudo strychnine, strychnine N oxide, strychnine N oxide and other alkaloids. Strychnine can competitively bind to glycine receptors in the spinal cord, blocking glycine has an inhibitory effect on the spinal cord, and can increase the tension of skeletal muscles; small doses of strychnine can excite the sensory analyzer of the cerebral cortex, making vision, hearing and smell Sharper. Strychnine nitrate injection is a species included in the second part of the Pharmacopoeia, with specifications of 1ml: 1mg and 1ml: 2mg. It is clinically used for the treatment of barbiturate poisoning, hemiplegia, and amblyopia.

The water extract of Nyx nuxica is very turbid, and it is a complex solid-liquid dispersion system, which is a mixed dispersion system composed of true solution, colloidal solution, emulsion and suspension. The microparticles of the water extract of Nyxa nuxicae can be divided into medicinal dregs microparticles (medicinal material tissue), multi-molecular aggregates of insoluble and insoluble components, cell fragments and aggregates according to the composition. Particles generally have hydrophilicity, charge and electric double layer, and there are interactions such as Van der Waals force, electric double layer mutual repulsion, solvation, hydrophobization, steric hindrance effect and other interactions between particles; Seed medicinal materials contain a large amount of water-soluble macromolecules such as starch and protein. Water-soluble macromolecules are natural surfactants, which have the functions of solubilizing, suspending, emulsifying, and wetting, and can be used as protective materials for hydrophobic colloids. Therefore, insoluble components, emulsion droplets, and solid particles have strong stability in water. The surface of Nuxynum is covered with fine and dense hairs, and its water extract contains a large amount of hairs, which are difficult to remove even by ethanol precipitation. After concentrating the water extract of Nyxa nuxica, adjust the pH value to alkaline, and it is very easy to emulsify during the extraction process with a lipophilic organic solvent, and the extraction operation is difficult to complete. The organic flocculant is a kind of high molecular weight polymer, its molecular weight is very large, and some active functional groups on the long carbon chain can absorb the particles of the water extract of Nuxebra chinensis. Since the flocculant is a long linear structure with many functional groups, it can adsorb multiple particles on the same molecule, so it acts as a link between the particles. This effect is called bridging. Therefore, the flocculant can link many particles together to form a floc, which gradually grows into a larger floc, thus accelerating the settling speed of the particles. After adsorption and clarification, the water extract of Nuxebra chinensis can change from a turbid state to a clear liquid, and the impurities in the extract are greatly reduced.

Contents of the invention

The purpose of the present invention is to provide an environment-friendly and low-cost method for extracting strychnine from Nuxychnium.

The object of the present invention is achieved through the following technical solutions, comprising the following steps:

(1) Nuxychnium coarse powder (all passing through a 10-mesh sieve, no more than 20% of the powder passing through a 50-mesh sieve), water reflux extraction, and concentrated extract;

(2) The concentrated solution is added with a polymer flocculant for adsorption and clarification;

(3) add alkali to the clarified liquid to adjust the alkalinity, and collect the precipitate A;

(4) Precipitate A is dissolved with dilute acid, the insoluble matter is filtered off, and the filtrate is adjusted to be alkaline to precipitate Precipitate B;

(5) Dilute hydrochloric acid dissolves the precipitate B, crystallizes, and obtains strychnine hydrochloride coarse crystals;

(6) Recrystallization.

Step (1) The amount of water used is 5-16 times the mass of Nuxyche, heated to reflux and extracted 1-4 times, and the time is 60-180 minutes; the concentration can be at room temperature or under reduced pressure, preferably under reduced pressure; the concentration ratio is Qianzi coarse powder: concentrated solution = 1g: 2-10ml.

Step (2) The flocculant can be gelatin, sodium alginate, agar, chitin and its derivatives, chitosan, 101 fruit juice clarifying agent, polycondensate, ZTC1+1 natural clarifying agent, crospovidone, polyvinyl alcohol A kind of in sodium acrylate, polyethylene terephthalate phenol, preferred flocculant is chitosan; Concrete is the acetic acid solution that adds 1% chitosan (1g chitosan is dissolved in 100ml1% acetic acid solution) 10-50ml, preferably 20-35ml; the flocculation temperature is 20-90°C, preferably 60-80°C, and the clarification time is 30-300 minutes.

The alkali used in step (3) can be alkaline substances such as sodium hydroxide, potassium hydroxide, calcium hydroxide and ammonia water, preferably 5-15% sodium hydroxide.

The dilute acid used in step (4) can be sulfuric acid, phosphoric acid and other 0.1-15% inorganic medium strong acid, preferably 1-5% sulfuric acid; used alkali is the same as step (3).

According to literature reports, the classic method of extracting strychnine from Strychnine is as follows: Soak Strychnine with lime water, then use benzene as a solvent to extract and recover most of the benzene, then extract with hydrochloric acid, the extract solution precipitates strychnine coarse crystals, and recrystallizes Obtain High Purity Strychnine Hydrochloride. The disadvantages are that the price of the solvent is high, the environment is polluted, the safety is poor (benzene is highly toxic), and the equipment is strictly required to prevent solvent leakage. Compared with the traditional strychnine preparation technology, this method uses water as the extraction solvent, which has little environmental pollution; the production equipment has low requirements, no organic solvent is consumed, and the production cost is low. The solubility of strychnine in water is very small. Stychnine precipitates when the pH value of the water-extracted concentrate of Nuxychnium is adjusted to alkaline, but the precipitate contains a large amount of impurities, and subsequent preparation work is difficult to carry out. Therefore, the water-extracted concentrate of Nuxychnium Adsorption clarification is carried out, and the pH value of the clarified liquid is adjusted to alkaline, the impurity content in the precipitate is greatly reduced, which is convenient for subsequent refining. At the same time, strychnine contains the most another alkaloid - strychnine. Strychnine has a significantly higher solubility in water than strychnine, so it contains less in the precipitate. Compared with the traditional method for preparing strychnine, the product prepared by this method has high purity. Therefore the present invention, as a whole brand-new scheme, is very suitable for extracting and preparing strychnine from Semen Nuxychia.

Detailed ways

The present invention is further illustrated below by way of examples. It should be understood that the embodiments of the present invention are for illustration rather than limitation of the present invention. The simple improvements made to the present invention according to the essence of the present invention all belong to the protection scope of the present invention. The crystals obtained in each embodiment of the present invention all adopt high performance liquid chromatography to measure the content of strychnine, and the chromatographic conditions are as follows: chromatographic column C-18 column (4.6mm * 250mm, 5m), Dalian Yite Company; mobile phase is acetonitrile -Water (containing 0.01mol/L potassium dihydrogen phosphate and 0.005mol/L sodium heptanesulfonate, 10% phosphoric acid to adjust pH2.8) (21:79); detection wavelength: 260nm; column temperature: 40°C; flow rate : 0.8ml/min.

Embodiment one:

Get 200 grams of nux nuxya powder, add 2000ml of water and decoct for 2 hours for the first time, add 1600ml of water for decocting for 1.5 hours for the second time, add 1200ml of water for decocting and decoct for 1.0 hour for the third time. Leave to stand to remove the filter residue, combine the filtrates, and concentrate according to the concentration ratio of Nuxychon seed coarse powder: concentrated solution = 1g: 5ml; add 200ml of acetic acid solution containing 1% chitosan, and adsorb and clarify in a water bath at 80°C. Use 10% NaOH to adjust the pH value of the clarified solution to 12, and collect the precipitate A; dissolve the precipitate A with 5% H ₂ SO ₄ , filter to remove the insoluble matter, then adjust the pH value to 12 with 10% NaOH, and collect the precipitate b. Precipitate B was dissolved with 5% HCl, filtered and crystallized; the crude crystals were dissolved and recrystallized to obtain 0.86 g of 95.3% strychnine hydrochloride.

Embodiment two:

Get 200 grams of nux nuxya powder, add 1600ml of water and decoct for 2 hours for the first time, add 1200ml of water for decocting for 1.5 hours for the second time, add 1200ml of water for decocting for 1.0 hour for the third time. Leave to stand to remove the filter residue, combine the filtrates, concentrate according to the concentration ratio of Nuxychon seed coarse powder: concentrated solution = 1g: 4ml; add 250ml of acetic acid solution containing 1% chitosan, and adsorb and clarify in a water bath at 60°C. Use 10% NaOH to adjust the pH value of the clarified solution to 12, and collect the precipitate A; dissolve the precipitate A with 3% H ₂ SO ₄ , filter to remove the insoluble matter, then adjust the pH value to 12 with 10% NaOH, and collect the precipitate b. Precipitate B was dissolved with 5% HCl, filtered and crystallized; the crude crystals were dissolved and recrystallized to obtain 0.81 g of 94.9% strychnine hydrochloride.

Embodiment three:

Get 200 grams of Nuxychnium seed meal, add 2000ml of water and decoct for 2 hours for the first time, add water and decoct for 1600ml for 1.5 hours for the second time. Leave to stand to remove filter residue, combine filtrate, concentrate according to the concentration ratio of Nuxychon seed coarse powder:concentrate=1g:5ml; Add 220ml of acetic acid solution containing 1% chitosan, 80 ℃ water bath adsorption clarification. Use 10% NaOH to adjust the pH value of the clarified solution to 12, and collect the precipitate A; dissolve the precipitate A with 5% H ₂ SO ₄ , filter to remove the insoluble matter, then adjust the pH value to 12 with 10% NaOH, and collect the precipitate b. Precipitate B was dissolved with 5% HCl, filtered and crystallized; the crude crystals were dissolved and recrystallized to obtain 0.73 g of 94.7% strychnine hydrochloride.

Embodiment four:

Get 200 grams of Nuxychnium seed meal, add 2000ml of water and decoct for 2 hours for the first time, add water and decoct for 1600ml for 1.5 hours for the second time. Leave to stand to remove the filter residue, combine the filtrates, and concentrate according to the concentration ratio of Nuxychon seed coarse powder: concentrated solution = 1g: 4ml; add 180ml of acetic acid solution containing 1% chitosan, and adsorb and clarify in a water bath at 80°C. Use 10% NaOH to adjust the pH value of the clarified solution to 12, and collect the precipitate A; dissolve the precipitate A with 5% H ₂ SO ₄ , filter to remove the insoluble matter, then adjust the pH value to 12 with 10% NaOH, and collect the precipitate b. Precipitate B was dissolved with 5% HCl, filtered and crystallized; the crude crystals were dissolved and recrystallized to obtain 0.71 g of 95.7% strychnine hydrochloride.

Comparative example

Take 200 grams of nux nuxya powder, soak in 300ml of lime water, add 2000ml of chloroform for the first time and decoct for 2 hours, add 1600ml of chloroform for the second time and decoct for 1.5 hours, add chloroform for the third time and decoct 1200ml was decocted for 1.0 hour, combined filtrates, recovered chloroform to 400ml, extracted with 40ml 6% HCl, and the extract crystallized; the crude crystals were dissolved and recrystallized to obtain 0.92 g of 91.3% strychnine hydrochloride.

Claims (8)

1. from Yunnan Dog Button, extract the method for Strychnine, it is characterized in that, may further comprise the steps:

(1) Yunnan Dog Button meal, the water refluxing extraction, extracting solution concentrates, and concentrated ratio is Yunnan Dog Button meal: liquid concentrator=1g: 2-10ml;

(2) liquid concentrator adds the polymeric flocculant adsorption clarification, and described polymeric flocculant is a chitosan;

(3) clear liquor is regulated the pH value to 10-13, collecting precipitation A;

(4) 0.1-15% sulfuric acid or phosphoric acid solution dissolution precipitation A, the elimination insolubles, filtrating is regulated the pH value to 10-13, separates out precipitate B;

(5) diluted hydrochloric acid dissolution precipitate B, crystallization gets the strychnine hydrochloride coarse crystallization;

(6) recrystallization promptly gets finished product.

2. method according to claim 1 is characterized in that, described Yunnan Dog Button meal is no more than 20wt% all through 10 mesh sieves through 50 mesh sieve powder.

3. method according to claim 1 is characterized in that, step (1) water consumption is 5-16 a times of Yunnan Dog Button meal quality, heating and refluxing extraction 1-4 time, each 60-180 minute.

4. method according to claim 1; It is characterized in that; Earlier the 1g chitosan is dissolved in the acetate of 100ml 1%, obtains the acetic acid soln of chitosan, in every 100ml liquid concentrator, add the acetic acid soln 10-50ml of described chitosan again; Flocculation temperature is 20-90 ℃, and settling time is 30-300min.

5. method according to claim 4 is characterized in that, every 100ml liquid concentrator adds the acetic acid soln 20-35ml of described chitosan, and temperature is 60-80 ℃.

6. method according to claim 1 is characterized in that, step (4) is middle with 1-5% sulfuric acid dissolution precipitate A.

7. method according to claim 1 is characterized in that, when step (3) and step (4) adjust pH with sodium hydroxide, Pottasium Hydroxide, calcium hydroxide or ammonia soln.

8. according to claim 1 or 7 described methods, it is characterized in that, when step (3) and step (4) adjust pH with the sodium hydroxide solution of 5-15%.