CN103393780A - Extraction method of high-purity coptis total alkaloid - Google Patents
Extraction method of high-purity coptis total alkaloid Download PDFInfo
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Abstract
The invention relates to an extraction method of high-purity coptis total alkaloid, which comprises the following steps: preparing a raw material (coptis or coptis fibril or coptis ash), pulverizing (not required if the raw material is coptis fibril or coptis ash), immersing in 0.1-5% sulfuric acid, heating and extracting four times, filtering, neutralizing with calcium oxide (or calcium hydroxide), filtering, washing the precipitate, preconcentrating, regulating the acid, precipitating with sodium chloride, filtering, recovering alkaloid from the mother liquor, and drying the precipitate to obtain the coptis total alkaloid product. The main active components of the product are coptis effective components, such as berberine, coptisine, palmatine, epiberberine, jateorhizine and the like; the coptis total alkaloid content is more than 50%; and the berberine content is more than 25%. The product provided by the invention has favorable actions of lowering blood sugar and blood fat, losing weight and the like, and is an ideal raw material for treating diabetes and cardiovascular diseases.
Description
Technical field
The invention belongs to the biological extraction technology, be specifically related to a kind of high-purity Rhizoma Coptidis total alkaloids extractive technique.
Background technology
Rhizoma Coptidis begins to be stated from
Shennong's Herbal, classify as top grade.The Rhizoma Coptidis bitter in the mouth, cold in nature, the function of pathogenic fire purging, detoxifcation, heat clearing away, dampness is arranged.Be used for dysphoria with smothery sensation coma, vexed insomnia, damp and hot feeling of fullness, vomiting, stomachache dysentery, conjunctival congestion toxic swelling, aphtha of the mouth and tongue, eczema, scald, haematemesis, epistaxis etc.The modern pharmacy result of study shows, the Rhizoma Coptidis main active is Rhizoma Coptidis total alkaloids, mainly comprises berberine (berberine), palmatine, coptisine, epiberberine and jateorhizine etc. (" Chinese pharmacopoeia 2010 editions); Rhizoma Coptidis (element) has the pharmacologically active widely such as blood fat reducing and blood sugar lowering.Nearest research discovery, except berberine, Rhizoma Coptidis related alkaloids active component (coptisine, palmatine etc.) also has the effect (Hou Hong etc. such as blood fat reducing and blood sugar lowering.Rhizoma Coptidis alkaloid hyperlipidemia disease and atherosclerosis experimentation.The time precious traditional Chinese medical science traditional Chinese medicines, 2011,22(10): 2462.); Also find simultaneously, highly purified Rhizoma Coptidis alkaloid safety is very high, and the Rhizoma Coptidis alkaloid crude product will cause the safety issues (Jun Yi etc. Safety evaluation of main alkaloids from Rhizoma Coptidis. Journal of Ethnopharmacology, 2013.145:303-310) such as liver function rising.Therefore, extract highly purified Rhizoma Coptidis total alkaloids and have good exploitation value, and the Rhizoma Coptidis alkaloid of low-purity value is very little.In addition, the Rhizoma Coptidis price is very expensive, and the yield that improves Rhizoma Coptidis total alkaloids is reduce production costs and improve the key of overall economic efficiency.
At present, about the existing more bibliographical information of the extraction process technology of Rhizoma Coptidis total alkaloids.
Chinese patent literature (200510044345.8) has been reported a kind of Rhizoma Coptidis total alkaloids extractive technique, mainly comprises: Rhizoma Coptidis, and water decocts, and upper macroporous resin purifies, washing, the aquiferous ethanol eluting, reclaim ethanol, and concentrate drying, obtain the processes such as product.Its Rhizoma Coptidis total alkaloids content reaches 25～100%.According to our research experience, the direct water of Rhizoma Coptidis decocts, and the extraction ratio of the total alkaloidss such as berberine is poor; On Rhizoma Coptidis alkaloid, after resin, during eluting, resin is difficult to 100% regeneration, and the resin utilization rate is not high; While reclaiming ethanol, ethanol is loss and high energy consumption etc. inevitably, causes cost rising etc.
Chinese patent literature (
200810069671.8) reported a kind of coptis chinensis total alkaloid extracting technique technology, mainly comprise: raw material (Rhizoma Coptidis or Rhizoma Coptidis fibrous root or leaf of Rhizoma Coptidis) and---pulverize (as for Rhizoma Coptidis fibrous root or leaf of Rhizoma Coptidis, not pulverizing) that------heating up and extract four times,---pre-concentration---purifies---sodium chloride and high-valency metal salt precipitation---filtration---oven dry---Rhizoma Coptidis total alkaloids product to add appropriate 0.01～10% soak with sulphuric acid.The main active of product is the Rhizoma Coptidis effective ingredient such as berberine, coptisine, jateorhizine, palmatine, epiberberine, and Rhizoma Coptidis total alkaloids content is more than 20%, and wherein the content of berberine is more than 10%.The Rhizoma Coptidis total alkaloids content (25%) on the low side that this Technology is produced, Product Safety is not high; Also contain a large amount of alkaloids in mother solution after extract total alkaloids, be not recovered utilization, the alkaloid total recovery is not high; In order to improve the purity of Rhizoma Coptidis total alkaloids, need to utilize adsorbent (as active hargil, silica gel, active carbon or various macroporous resins etc.) to purify, and the operation such as recrystallization, technique is comparatively complicated, and production cost is high.
Chinese patent literature (02103880.5) has been reported extraction process and the new purposes thereof of Rhizoma Coptidis total alkaloids, mainly comprise: the Rhizoma Coptidis water soaking and the time ultrasonic Treatment, carrying out total alkaloids under the warm macerating condition extracts, the gained extracting solution carries out concentrating under reduced pressure, then regulate the pH value of concentrated extracting solution with concentrated hydrochloric acid, add again sodium chloride, standing, then by the precipitate in sucking filtration or centrifuge dripping collection extracting solution, precipitate is dried, precipitate after oven dry is pulverized, and can obtain Rhizoma Coptidis total alkaloids hydrochlorate finished product.This explained hereafter is not owing to there is no purification process, and the purity of total alkaloids is not high; Simultaneously, due to the total alkaloids that does not reclaim in mother solution, the yield of total alkaloids is not high yet.
Chinese patent literature (200610024364.9) has been reported a kind of total alkaloids of meadowrueleaf corydalis root and purification process and pharmaceutical composition, mainly comprise: filter after the total alkaloids of meadowrueleaf corydalis root crude extract is dissolved with sour water, filtrate is passed through macroporous adsorptive resins, first water carries out eluting, then carry out eluting with the ethanol of 10-45%, collect the eluent of ethanol part, concentrated, be drying to obtain total alkaloids of meadowrueleaf corydalis root.This technique needs a large amount of ethanol elution purification, and production cost is difficult to control.
Chinese patent literature (201110053453.7) has been reported a kind of method of utilizing polyamide separation and purification Rhizoma Coptidis alkaloid, mainly comprise: the Rhizoma Coptidis crude extract goes up polyamide column after mixing sample with polyamide, with the dichloromethane eluting or with the mixed solvent gradient elution of dichloromethane and methanol, with thin layer chromatography check stream part, merge same stream part, drying, i.e. separable seven alkaloids such as berberine, palmatine, coptisine, Columbamine, jateorhizine, magnoflorine, Groenlandcine that obtain.What this Technology was separated is the Rhizoma Coptidis alkaloid monomer, and owing to relating to the very large dichloromethane equal solvent of toxicity in the separation and purification process, safety is difficult to ensure.
Chinese patent literature (200810218824.0) has been reported the application of Rhizoma Coptidis total alkaloids in preparing the diabetic complication medicine, mainly comprises: 1) Rhizoma Coptidis is ground into coarse powder; 2) 5-10 doubly measures 60-80% ethanol with Rhizoma Coptidis coarse powder reflux, extract, 1-3 time, and 1-2h/ time, gradation is filtered, merging filtrate.Concentrating under reduced pressure, drying, obtain Rhizoma Coptidis extract; 3) Rhizoma Coptidis extract is added 5 times of amount 0.5% sulfuric acid dissolutions, filter, filtrate is transferred pH9 with lime cream respectively, filters, and with hydrochloric acid, transfers respectively pH1～2, adds sodium chloride and makes salinity reach 10%, shakes up, and is standing, obtains Rhizoma Coptidis total alkaloids.This technique does not relate to the problems such as recovery of Rhizoma Coptidis total alkaloids in the rear mother solution of Rhizoma Coptidis total alkaloids precipitation yet.
Chinese patent literature (201110243033.5) has been reported the purposes of Rhizoma Coptidis total alkaloids effervescent tablet method for making and treatment disease in the female sexual system, mainly comprise: get Rhizoma Coptidis plant herb appropriate, be crushed to coarse powder, adding 4～15 times of amount concentration is 0.1～1% aqueous sulfuric acid, soak at room temperature extracted 24 hours, 2～5 filtrations; Get extracting solution and add lime cream to transfer pH7, placed 8～12 hours, filter; Get extracting solution and add concentrated hydrochloric acid to transfer pH2-3, placed 8～12 hours, filter: get precipitation and add 50 times of water gagings to boil dissolving, lime cream is transferred pH8-9, filtered while hot; Get filtrate washing, drain, drying, obtaining Rhizoma Coptidis total alkaloids is a; 2～5 parts of polyethylene glycol 6000s add 5～15 parts of dissolve with ethanols, add 15～30 parts of sodium bicarbonate, and obtaining sodium bicarbonate, Polyethylene Glycol, alcohol mixeding liquid is b; Adopt the spray starch absorption dehydration method of microencapsulation preparation method, with b through atomizer spray in the rotation coating pan of splendid attire a, cross finally No. two sieve granulate and become c; Citric acid is crossed and sieved into granule and c for No. two and cross together with No. seven sieves and mix, tabletting, every heavy 1g, feeding port place infrared ray radiation during tabletting.This invention is easy to carry, rapid-action, treatment disease in the female sexual system effect and definite and high curative effect.After this technique does not relate to the Rhizoma Coptidis total alkaloids precipitation yet, the problems such as recovery of Rhizoma Coptidis alkaloid in mother solution.
Chinese patent literature (201010246367.3) has been reported the new purposes of coptis total alkaloid extract, mainly comprises: the preparation method of coptis total alkaloid extract; After so-called Rhizoma Coptidis total alkaloids refers to that Rhizoma Coptidis is with certain water gaging heating extraction, be concentrated into dried.The Rhizoma Coptidis total alkaloids that this technique obtains is actually the full extractum of Rhizoma Coptidis, and purity is very low.
Chinese patent literature (200710099687.9) has been reported total alkaloids of meadowrueleaf corydalis root and preparation method thereof and purposes, the production method of its total alkaloids is: after raw material adds 0.1～1% sulphuric acid extraction, extracting solution adds the sodium chloride precipitation and saltouts, obtain total alkaloids and be dissolved in again ethanol, the decolouring purification, obtain the higher total alkaloids of purity.After this technique precipitation total alkaloids, do not consider the recovery of total alkaloids in mother solution, affect final yield; Crude product is dissolved in ethanol, and the decolouring purification, will further affect the yield of total alkaloids.
" Rhizoma Coptidis alkaloid extracts and purifying process research " (Tu Yaosheng etc.New Chinese medicine and clinical pharmacology.2012,23(2): 208) reported that a kind of Rhizoma Coptidis total alkaloids extracts and purification process, mainly comprises: the Rhizoma Coptidis decoction pieces adds the sulfuric acid solution of 8 times of amount 1.5 %, decocts each 40 min 3 times; Rhizoma Coptidis extract Ca (OH)
2Regulate pH5～6, sucking filtration, it is that every mL contains the 0.24g crude drug that the filtrate heating is concentrated into concentration, sucking filtration, filtrate salt adding acid for adjusting pH 1.5～2, add 5% sodium chloride solution and make dissolving, standing over night in refrigerator, sucking filtration, filtering residue vacuum drying (50 ℃), collect purified.Rhizoma Coptidis total alkaloids extraction ratio 93% left and right, total alkaloids yield 60% left and right, total alkaloids purity 84% left and right.This technique total alkaloids yield (60%), and the purity of product is also general.
In sum, although it is very many to extract the Technology of Rhizoma Coptidis total alkaloids,, ubiquity total alkaloids yield is not high, and perhaps purity is undesirable, and perhaps complex process, perhaps relate to the problems such as toxic solvent in the course of processing.
In the art, extraction ratio refers to be dissolved into the biological alkali number in solution from Rhizoma Coptidis, and yield is the product volume that finally obtains after extracting operation.But the amount that is dissolved in solution is many, and what might not obtain finally is many, because can have various losses in subsequent processes, some loss meetings are very large.
And from the report of prior art as can be known, prior art does not consider all in mother solution that alkaloid reclaims and precipitation is taken away alkaloidal recovery, be mainly to have blind spot in research: namely many research workers did not carry out systematic analysis, and do not know how many alkaloids sealed Belt walks, how many alkaloids mother solution takes away, namely and do not know that alkaloid lost in which in step, thereby do not want to reclaim alkaloidal problem.
Summary of the invention
The object of the present invention is to provide a kind of high-purity Rhizoma Coptidis total alkaloids extracting method, it, take Rhizoma Coptidis and by-product thereof as raw material, namely extracts the total alkaloids in Rhizoma Coptidis and Rhizoma Coptidis fibrous root and Rhizoma Coptidis lime-ash, improves simultaneously purity and the yield of its final products.
The present invention is take Rhizoma Coptidis and coptis plant as raw material, adopts sulfuric acid solution to soak to extract to produce Rhizoma Coptidis total alkaloids, and described method comprises:
1), raw material is prepared
, with Rhizoma Coptidis or Rhizoma Coptidis fibrous root or Rhizoma Coptidis lime-ash removal silt, pulverize or shredding (as for Rhizoma Coptidis fibrous root or Rhizoma Coptidis lime-ash, not pulverizing or shredding), as the raw material of processing.
2), soak
Raw material is joined fermentation vat or extract in still, adding appropriate (3～15 times of volumes) concentration is that 0.1～5% aqueous sulfuric acid (W/V) soaked 1～48 hour.
3), extract
After immersion, be warmed up to 20～100 ℃, insulation was extracted 0.1～5 hour, extracted four times.For the first time and for the second time extracting solution is for the production of product; Extracting solution is used for the soak of next group raw material for the third time, and soak is directly as primary extracting solution; The 4th extracting solution is used for the extracting solution for the second time of next group raw material.
4), feed liquid neutralization
Will be for the first time and for the second time extracting solution merge, filter; Filtrate uses Calx (or calcium hydroxide) neutralization to arrive the pH=2 of solution～12, filters; Residue is used in right amount (0.1～3 times of level of residue) water washing 1～3 time again, reclaims the alkaloid that residue is taken away.Cleaning mixture stays, and to the 8th step and total alkaloids mother liquor of precipitation of ammonium, merges, and utilizes macroporous resin treatment.
5), saltout
With the pH=1 of neutralizer use concentrated hydrochloric acid regulator solution～5; Then, add the sodium chloride of liquor capacity 1～20% ratio, low temperature (0～30 ℃) was placed 1～48 hour, the precipitation total alkaloids.
For the 4th) step filtration after neutralizer, also can carry out pre-concentration, namely carry out 1～20 times of concentrating under reduced pressure, and then carry out the 5th the step.
6), filter and wash
Precipitation (total alkaloids) adopts natural filtration or centrifugal filtration,, with the suitable quantity of water washing, is Rhizoma Coptidis total alkaloids simultaneously.
7), total alkaloids mother liquid disposal
The washing liquid of the mother solution after the precipitation total alkaloids and the operation of the 4th step merges, according to macroporous resin on the speed of 0.1～5% times of resin volume per minute, after macroporous resin adsorption, with the water washing resin of 0.1～5 times of macroporous resin volume; Then 10～90% ethanol elution, after reclaiming ethanol, obtain Rhizoma Coptidis total alkaloids.
8), oven dry
Merge the Rhizoma Coptidis total alkaloids that the operation of two steps obtains, oven dry, be high-purity Rhizoma Coptidis total alkaloids product.The main active of this product is the Rhizoma Coptidis total alkaloidss such as berberine (berberine), coptisine, epiberberine, palmatine, jateorhizine.The yield of total alkaloids is more than 90%, and the content of Rhizoma Coptidis total alkaloids is more than 50%, and wherein the content of berberine is more than 25%.
Under normal circumstances, in this product, total alkaloid content is generally 90% left and right, and berberine content can reach 45%, and the other biological alkali content can reach 45%, is more than 9 times of total alkaloid content in Rhizoma Coptidis.
Alkaloid yield of the present invention is high, and the yield of total alkaloids is more than 90%, and is simple to operate, and industrial cost is reduced greatly, and productivity effect significantly improves; The product purity that the present invention produces is high, generally can reach more than 90%, and safety is fabulous; The Rhizoma Coptidis total alkaloids that the present invention obtains and composition thereof, very similar with the composition of Rhizoma Coptidis total alkaloids, have pharmacological properties like Rhizoma Coptidis, have more preferably blood sugar lowering, blood fat reducing and fat-reducing texts than single Rhizoma Coptidis.
Product of the present invention (Rhizoma Coptidis total alkaloids) can be used as the succedaneum of the products such as Rhizoma Coptidis, Rhizoma Coptidis concentrated product, berberine, can be used for the treatment of diabetes, hyperlipidemia, obesity and cardiovascular disease.
Below Rhizoma Coptidis total alkaloids and the contrast experiment of common berberine aspect safety and treatment relevant disease that relevant the present invention obtains:
1., subchronic toxicity testing
Test material is Rhizoma Coptidis total alkaloids (content 90%), berberine (content 95%), the Rhizoma Coptidis total alkaloids crude product (total alkaloid content 40%) that the present invention makes.
The subchronic toxicity testing method is carried out with reference to " natural drug (Chinese medicine) new drug research guideline ": the SD rat is divided into four groups, be respectively Normal group, Rhizoma Coptidis total alkaloids group, berberine group, Rhizoma Coptidis total alkaloids crude product group, every group 10, dosage is 1g/Kg; Continuous irrigation was fed 3 months, then adopted the biochemical indicators such as fasting blood monitoring liver function.
From the table can see, compare with Normal group, the Rhizoma Coptidis total alkaloids sterling on liver function without any impact; The liver also not impact of berberine on laboratory animal; The liver function of Rhizoma Coptidis total alkaloids crude product group mouse obviously raises, and the Rhizoma Coptidis total alkaloids that shows low-purity has adverse effect to the liver of animal.The result of this result and bibliographical information similar (Jun Yi etc. Safety evaluation of main alkaloids from Rhizoma Coptidis. Journal of Ethnopharmacology, 2013.145:303-310).
2., hypolipidemic activity experiment
Test material is Rhizoma Coptidis total alkaloids (total alkaloid content 90%), berberine (content 95%), the Rhizoma Coptidis total alkaloids crude product (total alkaloid content 40%) that the present invention makes.
The lipid-lowering test method is carried out with reference to " natural drug (Chinese medicine) new drug research guideline ": Golden Hamster is divided into 5 groups, and one group (10) give normal feedstuff, and one group (40) give high lipid food; After 4 weeks, detect blood lipids index, then the Golden Hamster of modeling success is divided into 4 groups (8～10 every group): high fat matched group, Rhizoma Coptidis total alkaloids group, berberine group, Rhizoma Coptidis total alkaloids crude product group.The medicine group gives the 500mg/Kg medicine; Continuous irrigation fed for 4 weeks, then adopted fasting blood and detected blood lipids index.
Can see from table, compare with Normal group, each test group blood fat all has rising, shows the modeling success; Compare with high fat group, each medicine group cholesterol (TC) all descends to some extent, shows hypolipidemic activity is all arranged; Wherein the hypolipidemic activity of high-purity total alkaloids is better than berberine, also is better than the total alkaloids crude product.
Above-mentioned result of study shows, no matter from safety still from the drug effect aspect, highly purified Rhizoma Coptidis total alkaloids value of exploiting and utilizing obviously is better than the Rhizoma Coptidis total alkaloids of low-purity.
The present invention has the following advantages:
1., this Technology is take Rhizoma Coptidis and by-product thereof as raw material, especially, take by-products such as Rhizoma Coptidis fibrous root and Rhizoma Coptidis lime-ash as raw material, belongs to the comprehensive utilization of resources scope, low cost product, the course of processing is simple, is easy to preparation.
2., in the product that obtains of this Technology except berberine, still contain the Rhizoma Coptidis related alkaloids such as a large amount of palmatines, coptisine, epiberberine, jateorhizine, biological value is higher, the utilization of resources is more abundant.
3., extracting solution is by Calx (or calcium hydroxide) neutralisation of sulphuric acid, utilizes calcium sulfate absorption to remove impurity in extracting solution, guaranteed the quality of salt precipitation total alkaloids.Compare with other impurity and purification techniques, this technological operation is simple, and is with low cost.
4., utilize mother solution after macroporous resin treatment Rhizoma Coptidis total alkaloids precipitation and the washing liquid of calcium sulfate precipitation, not only reclaimed the total alkaloids that mother solution and calcium sulfate precipitation are taken away, guaranteed the yield of Rhizoma Coptidis total alkaloids; And, by after macroporous resin adsorption, wash remove impurity, significantly improved the purity of total alkaloids.The overall extraction ratio of this technique Rhizoma Coptidis total alkaloids is more than 90%, the content of total alkaloids (purity) 90% left and right.Simple to operate, practicality.
5.,This technology utilization calcium sulfate precipitation adsorption-edulcoration, reclaim the most of Rhizoma Coptidis alkaloid (60% left and right) that extracts; The recycling macroporous resin adsorption reclaims the Rhizoma Coptidis alkaloid in mother solution and precipitation, has not only reduced cost, has improved product purity, and has guaranteed total recovery.Technology is simple, and comparative costs is low.
The specific embodiment
Embodiment 1:
1 kilogram of Rhizoma Coptidis is pulverized or section, adds the sulfuric acid solution of 3 liter 5%, soaks after 1 hour, is warmed up to 100 ℃ of reflux, extract, 0.1 hour, filters; Residue is warmed up to 100 ℃ of extractions three times with the sulfuric acid solution of 3 liter 5% again; Merge for the first time with the second extracting solution (three times extract and extract the processing that is used for the next group raw material four times), supernatant is separated (perhaps filtration obtains supernatant) after cooling; Supernatant utilizes Calx (calcium oxide) neutralization to pH=2, filters, and precipitation utilizes the water washing of 0.1 times of precipitation capacity to precipitate 3 times; Neutralizer utilizes the pH=1 left and right of concentrated hydrochloric acid regulator solution, and the sodium chloride of interpolation 1% fully stirred rear room temperature (30 ℃) static 48 hours; Filter, precipitation, with suitable quantity of water washing three times, obtains total alkaloids; The washing liquid of mother solution and neutralization precipitation merges, and utilizes macroporous resin adsorption (upper prop speed is 0.1% times of resin volume),, with 5 times of water washings, then uses 10% ethanol elution; Reclaim ethanol, solid and the total alkaloids that precipitates above merge; Under 50～70 ℃, oven dry, obtain product.High performance liquid chromatography (HPLC) analysis result shows, in product, total alkaloid content 96%, and wherein berberine content 48%, other biological alkali content 48%; The yield 92% of Rhizoma Coptidis total alkaloids.
Embodiment 2
1 kilogram of Rhizoma Coptidis fibrous root, add the sulfuric acid solution of 10 liter 1%, soaks after 12 hours, is warmed up to 60 ℃ and extracted 1 hour, filters; Residue is warmed up to 60 ℃ of extractions three times with the sulfuric acid solution of 10 liter 1% again; Merge for the first time with the second extracting solution (three times extract and extract the processing that is used for the next group raw material four times), supernatant is separated (perhaps filtration obtains supernatant) after cooling; Supernatant utilizes Calx (calcium oxide) neutralization to pH=12, filters, and precipitation utilizes the water washing of 3 times of precipitation capacities to precipitate 1 time; 5 times of neutralizer concentrating under reduced pressure, filter, and about the pH=5 of filtrate with the concentrated hydrochloric acid regulator solution, the sodium chloride of interpolation 10% fully stirred rear low temperature (0 ℃) static 1 hour; Filter, precipitation, with suitable quantity of water washing three times, obtains total alkaloids; The washing liquid of mother solution and neutralization precipitation merges, and utilizes macroporous resin adsorption (upper prop speed is 5% times of resin volume),, with 1 times of water washing, then uses 90% ethanol elution; Reclaim ethanol, solid and the total alkaloids that precipitates above merge; Under 50～70 ℃, oven dry, obtain product.High performance liquid chromatography (HPLC) analysis result shows, in product, total alkaloid content 80%, and wherein berberine content 40%, other biological alkali content 40%; The yield 93% of Rhizoma Coptidis total alkaloids.
Embodiment 3
1 kilogram of Rhizoma Coptidis lime-ash, add the sulfuric acid solution of 15 liter 0.1%, soaks after 48 hours, is warmed up to 20 ℃ (, if temperature surpasses 20 ℃, can heat up) and extracted 5 hours, filters; Residue is warmed up to 20 ℃ of extractions three times with the sulfuric acid solution of 15 liter 0.1% again; Merge for the first time with the second extracting solution (three times extract and extract the processing that is used for the next group raw material four times), supernatant is separated (perhaps filtration obtains supernatant) after cooling; Supernatant utilizes Calx (calcium oxide) neutralization to pH=6, filters, and precipitation utilizes the water washing of 1 times of precipitation capacity to precipitate 2 times; 20 times of neutralizer concentrating under reduced pressure, filter, and about the pH=3 of filtrate with the concentrated hydrochloric acid regulator solution, the sodium chloride of interpolation 20% fully stirred rear low temperature (10 ℃) static 12 hours; Filter, precipitation, with suitable quantity of water washing three times, obtains total alkaloids; The washing liquid of mother solution and neutralization precipitation merges, and utilizes macroporous resin adsorption (upper prop speed is 2% times of resin volume),, with 0.1 times of water washing, then uses 40% ethanol elution; Reclaim ethanol, solid and the total alkaloids that precipitates above merge; Under 50～70 ℃, oven dry, obtain product.High performance liquid chromatography (HPLC) analysis result shows, in product, total alkaloid content 50%, and wherein berberine content 25%, other biological alkali content 25%; The yield 95% of Rhizoma Coptidis total alkaloids.
Claims (6)
1. one kind take Rhizoma Coptidis and coptis plant as raw material, adopts sulfuric acid solution to soak the method for extracting production high-purity Rhizoma Coptidis total alkaloids, and described method comprises:
1), raw material is prepared
, with Rhizoma Coptidis or Rhizoma Coptidis fibrous root or Rhizoma Coptidis lime-ash removal silt, pulverize or shredding;
2), soak
Add aqueous sulfuric acid to soak raw material;
3), extract
After immersion, extract at least twice;
4), feed liquid neutralization
Will be for the first time and for the second time extracting solution merge, filter; Filtrate, with Calx or the calcium hydroxide pH=2 of solution～12 that neutralize, is filtered; Residue washes with water again, reclaims the alkaloid that residue is taken away, and obtains cleaning mixture;
5), saltout
With the pH=1 of neutralizer use concentrated hydrochloric acid regulator solution～5; Then, add the sodium chloride of liquor capacity 1～20% ratio, placed 1～48 hour under 0～30 ℃ of low temperature, the precipitation total alkaloids;
6), filter and wash
The total alkaloids that precipitation is obtained adopts natural filtration or centrifugal filtration, washes with water simultaneously, is Rhizoma Coptidis total alkaloids;
7), total alkaloids mother liquid disposal
The cleaning mixture that the mother solution that precipitation is obtained after total alkaloids and step 4) stay merges, according to macroporous resin on the speed of 0.1～5% times of resin volume per minute, after macroporous resin adsorption,, with the water washing resin of 0.1～5 times of macroporous resin volume, remove the impurity in total alkaloids; Then 10～90% ethanol elution, after reclaiming ethanol, obtain Rhizoma Coptidis total alkaloids;
8), oven dry
Merge the Rhizoma Coptidis total alkaloids that the operation of two steps obtains, oven dry, be high-purity Rhizoma Coptidis total alkaloids product.
2. the method for extraction production high-purity Rhizoma Coptidis total alkaloids according to claim 1, is characterized in that: for the 4th) neutralizer after the filtration in step, also can carry out pre-concentration, namely carry out 1～20 times of concentrating under reduced pressure, process carrying out for the 5th step.
3. the method for extraction production high-purity Rhizoma Coptidis total alkaloids according to claim 1 and 2 is characterized in that: it is 0.1～5% aqueous sulfuric acid (W/V) that soak time described 2) adds 3～15 times of volumes, concentration with raw material, soaks 1～48 hour.
4. the method for extraction production high-purity Rhizoma Coptidis total alkaloids according to claim 1 and 2 is characterized in that: the extraction of described step 3) is to be incubated after being warmed up to 20～100 ℃ to extract 0.1～5 hour.
5. the method for extraction production high-purity Rhizoma Coptidis total alkaloids according to claim 1 and 2 is characterized in that: being extracted as four times of described step 3), and for the first time and for the second time extracting solution is for the production of product; Extracting solution is used for the soak as the next group raw material for the third time, and directly as primary extracting solution; The 4th extracting solution is used for the extracting solution for the second time of next group raw material.
6. the method for extraction production high-purity Rhizoma Coptidis total alkaloids according to claim 1 and 2, it is characterized in that: the main active of Rhizoma Coptidis total alkaloids is that berberine is the Rhizoma Coptidis total alkaloidss such as berberine, coptisine, epiberberine, palmatine, jateorhizine, the content of total alkaloids is more than 50%, and wherein the content of berberine is more than 25%.
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Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103655664A (en) * | 2013-12-03 | 2014-03-26 | 辽宁中医药大学 | Preparation method of berberis poiretii total alkaloids extract |
| CN103751313A (en) * | 2014-01-28 | 2014-04-30 | 西南大学 | Traditional Chinese herbal medicine composite preparation for prevention and treatment of fish diseases |
| CN104327072A (en) * | 2014-11-25 | 2015-02-04 | 中国药科大学 | Method for extraction and preparation of jatrorrhizine and application of jatrorrhizine in preparation of medicine for prevention and treatment of colon cancer |
| CN104644793A (en) * | 2015-03-20 | 2015-05-27 | 西南大学 | Efficient extraction method of total coptis alkaloids |
| CN105596457A (en) * | 2016-03-01 | 2016-05-25 | 河南中医学院 | Traditional Chinese medicine preparation heart-fire clearing and restlessness relieving tablets for preventing and treating excess-heat anxiety disorder |
| CN106831758A (en) * | 2016-12-20 | 2017-06-13 | 长兴众化生物科技有限公司 | A kind of extracting method of high-purity coptisine |
| CN107126471A (en) * | 2017-05-15 | 2017-09-05 | 北京大学 | Treat pharmaceutical composition of diabetes and its production and use |
| CN109369529A (en) * | 2018-12-29 | 2019-02-22 | 西南大学 | Mother liquor is extracted as method, high-purity magnoflorine prepared therefrom and the application of raw material preparation high-purity magnoflorine using the coptis |
| CN110882246A (en) * | 2018-09-08 | 2020-03-17 | 西南大学 | Extraction method and application of coptis alkaloid with different biological activities |
| CN110960583A (en) * | 2018-09-29 | 2020-04-07 | 西南大学 | Pharmaceutical composition for treating acne and application thereof |
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| CN101429197A (en) * | 2008-12-17 | 2009-05-13 | 西南大学 | Extraction method for joint production of coptis chinensis with coptis chinensis fibrous root as raw material |
| CN101723950A (en) * | 2009-11-26 | 2010-06-09 | 西南大学 | Method for extracting coptisine |
| CN101972320A (en) * | 2010-10-21 | 2011-02-16 | 西南大学 | Method for extracting ferulic acid, chlorogenic acid and other aicd components from coptis chinensis franch |
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| CN101429197A (en) * | 2008-12-17 | 2009-05-13 | 西南大学 | Extraction method for joint production of coptis chinensis with coptis chinensis fibrous root as raw material |
| CN101723950A (en) * | 2009-11-26 | 2010-06-09 | 西南大学 | Method for extracting coptisine |
| CN101972320A (en) * | 2010-10-21 | 2011-02-16 | 西南大学 | Method for extracting ferulic acid, chlorogenic acid and other aicd components from coptis chinensis franch |
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| CN103655664A (en) * | 2013-12-03 | 2014-03-26 | 辽宁中医药大学 | Preparation method of berberis poiretii total alkaloids extract |
| CN103751313A (en) * | 2014-01-28 | 2014-04-30 | 西南大学 | Traditional Chinese herbal medicine composite preparation for prevention and treatment of fish diseases |
| CN104327072A (en) * | 2014-11-25 | 2015-02-04 | 中国药科大学 | Method for extraction and preparation of jatrorrhizine and application of jatrorrhizine in preparation of medicine for prevention and treatment of colon cancer |
| CN104644793A (en) * | 2015-03-20 | 2015-05-27 | 西南大学 | Efficient extraction method of total coptis alkaloids |
| CN105596457A (en) * | 2016-03-01 | 2016-05-25 | 河南中医学院 | Traditional Chinese medicine preparation heart-fire clearing and restlessness relieving tablets for preventing and treating excess-heat anxiety disorder |
| CN106831758A (en) * | 2016-12-20 | 2017-06-13 | 长兴众化生物科技有限公司 | A kind of extracting method of high-purity coptisine |
| CN107126471A (en) * | 2017-05-15 | 2017-09-05 | 北京大学 | Treat pharmaceutical composition of diabetes and its production and use |
| CN110882246A (en) * | 2018-09-08 | 2020-03-17 | 西南大学 | Extraction method and application of coptis alkaloid with different biological activities |
| CN110960583A (en) * | 2018-09-29 | 2020-04-07 | 西南大学 | Pharmaceutical composition for treating acne and application thereof |
| CN109369529A (en) * | 2018-12-29 | 2019-02-22 | 西南大学 | Mother liquor is extracted as method, high-purity magnoflorine prepared therefrom and the application of raw material preparation high-purity magnoflorine using the coptis |
| CN109369529B (en) * | 2018-12-29 | 2022-03-04 | 西南大学 | Method for preparing high-purity magnoflorine by taking coptis chinensis extraction mother liquor as raw material, high-purity magnoflorine prepared by method and application |
| CN111686086A (en) * | 2020-07-24 | 2020-09-22 | 焦作福瑞堂制药有限公司 | Compound dandelion and scutellaria tablet and production process thereof |
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