CN101491631A - Method for separating verticine total alkaloids in traditional Chinese medicine extract - Google Patents
Method for separating verticine total alkaloids in traditional Chinese medicine extract Download PDFInfo
- Publication number
- CN101491631A CN101491631A CNA2007100984424A CN200710098442A CN101491631A CN 101491631 A CN101491631 A CN 101491631A CN A2007100984424 A CNA2007100984424 A CN A2007100984424A CN 200710098442 A CN200710098442 A CN 200710098442A CN 101491631 A CN101491631 A CN 101491631A
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- China
- Prior art keywords
- bulbus fritillariae
- total alkaloids
- fritillariae uninbracteatae
- separation
- bases total
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- 150000007949 saponins Chemical class 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
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- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
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- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a method for separating total alkaloid from traditional Chinese medicine, in particular a method for separating verticine total alkaloid from traditional Chinese medicine extract, which belongs to the field of traditional Chinese medicines. The method comprises the following technical proposal that the traditional Chinese medicine extract is taken and filtered, the pH value of the traditional Chinese medicine extract is adjusted to be between 1 and 7; filtrate is added to a cation exchange resin column, eluted with water to remove impurities and then eluted by use of 0.5 to 15 percent acid liquid; and eluent is collected, added with alkali for neutralization and desalted so as to prepare verticine total alkaloid. The method overcomes the deficiency that the prior art is low in extraction ratio, large in the amount of organic solvents, complex in process, incapable of mass production and the like, and can efficiently separate high-purity verticine total alkaloid from the traditional Chinese medicine extract.
Description
Technical field
The present invention relates to a kind of in the extraction separation method of pharmaceutically active ingredient, particularly relate to a kind of from Chinese medicine extraction liquid the method for extraction separation Bulbus Fritillariae Uninbracteatae bases total alkaloids, belong to the field of Chinese medicines.
Background technology
Chinese traditional medicine biology alkali is the class important substance that occurring in nature exists, be separated to kind more than 700 at present, they are maximum class determined curative effects in the Chinese medicine, broad-spectrum effective ingredient, especially cancer, hepatopathy and cardiovascular and cerebrovascular vessel, rheumatism major disease etc. there is unique curative effect, be used for anti-inflammation as the berberine in the Rhizoma Coptidis, ephedrine in the Herba Ephedrae is used to relieving asthma, reserpine in the Radix Rauvolfiae is used for blood pressure lowering, galantamine in the Bulbus Lycoridis Radiatae is effective in cure to poliomyelitis sequela, and contained morphine base is famous analgesics in the Semen Papaveris peel; Quinine alkali is valuable antipyretic; Capsaicin has many physiologically actives and strong and persistent anti-inflammatory analgesic action; Camptothecine in the Fructus seu radix camptothecae acuminatae (Fructus Camptothecae Acuminatae) and the vincristine in the Herba Catharanthi Rosei are used for antitumor etc.With kashmirine and peimine is the peimine Alkaloid of representative, be present in the liliaceous plant more, for example Bulbus Fritillariae Cirrhosae, Bulbus Fritillariae Thunbergii, Bulbus Fritillariae Pallidiflorae, Bulbus Fritillariae Ussuriensis, Hupeh Fritillary Bulb etc., this Alkaloid has very strong preventing phlegm from forming and stopping coughing effect, is the very high alkaloid of a class clinical value.
At present, contain the extraction of Chinese traditional medicine biology bases medical material, how according to alkaloidal physicochemical property, adopt The suitable solvent such as water, sour water, acid alcohol and alkali alcohol etc., utilize dipping, percolation, decoction, backflow, technology such as ultrasonic that the alkaloids composition is extracted, extraction process is more perfect, and the alkaloid extraction ratio can reach more than 90%.But because the relative amount of alkaloid in Chinese medicine lower (most content are 0.01%～1%), certainly will introduce a large amount of impurity class compositions during extraction, as a large amount of starch, natural gum, pectin, phlegmatic temperament, pigment etc., giving further discards the dross and selects the essential has brought very big difficulty, thereby real technical bottleneck just is how to be further purified the alkaloid that enrichment extracts.At present, the purification process of extensive use mainly is alkalization back organic solvent extractionprocess and macroporous adsorbent resin method (" Chemistry for Chinese Traditional Medicine ", Xiao Chonghou chief editor,, Shanghai science tech publishing house in 1997 in the alkaloid purifying process; " in the Chinese herbal medicine alkaloid extraction with separate ", Cai Yanhua, Sichuan chemical industry, 2005. (1) 39).
Organic solvent extractionprocess is to utilize the lipotropy alkaloid to be dissolved in the lipotropy organic solvent, and the water-soluble character of its salt, the alkaloid soda acid is transformed, utilize organic solvent (commonly used as benzene, chloroform, ether etc.) extraction, remove a large amount of impurity, organic solvent extractionprocess is used comparatively extensive, but impurity such as a large amount of neutrality in alkalization back and nonpolar pigment easily are brought into, therefore separation efficiency and purity are lower, and use a large amount of organic solvents (generally extracting 5 times), and (extractor efficient is not high in operation inconvenience, and easily emulsifying) not good (organic solvent toxicity is big in safety, and inflammable and explosive), be laboratory process, be not suitable for the big production of industry.
The macroporous adsorbent resin isolation technics, effective ingredient in the selective absorption Chinese medicine extraction liquid is removed impurity.Compare with technology with traditional impurity-removing method, can dwindle medication dose, improved the quality of preparation, this method to water solublity preferably flavone, saponin etc. good separation and purification effect is arranged, as Semen Ginkgo class preparation at present commonly used and ginsenoside's preparation etc.But make with extra care for alkaloidal, the deficiency of this law maximum is: at first be the absorption difficulty, last sample medicinal liquid must be a weak solution, and basicity will suit, the low then alkaloid of basicity still is an ionization state, the adsorption rate of resin is low, the basicity height, and alkaloid is free type, macromole alkaloid poorly water-soluble and separating out, still can't upper prop, suitable alkaloid scope is very little, and kind is very little; Secondly, the nonpolar electrostatic absorption principle of macroporous adsorbent resin is too poor to the separation selectivity of alkaloid active ingredient and oil-soluble impurities, and in the solvent elution process owing to there is not a specific eluting solvent, alkaloid and a large amount of oil-soluble impurities are often eluted together, and the total alkaloids purity that final refining obtains is not high.
Also having emerging ion exchange resin isolation technics, is the purpose that reaches separation and purification by ion-exchange reactions.At present the technology that generally adopts in field of Chinese medicines institute is, after will containing alkaloidal solution and crossing post, with ammoniacal liquor or NaOH eluant solution, behind the collection eluent again with the organic solvent extraction alkaloid; The resin that perhaps will go up sample is with dipping by lye, and then with organic solvent reflux, extract, alkaloid.But this method step is loaded down with trivial details, organic solvent extraction, resin column is carried out steps such as organic solvent reflux, extract, in industrial very difficult realization, and very low with the efficient of alkali liquor eluting, only stays in the level of prepared in laboratory small sample, also can't realize big production.
More than these methods, ubiquity cost height, organic solvent consumption are big, poor selectivity, total alkaloids purity is low and can't realize deficiency such as big production, therefore, purification technique is still " bottleneck " problem of Chinese medicine separating bio alkali.
Summary of the invention
The method that the purpose of this invention is to provide a kind of safe, low-cost, high efficiency extraction separation Bulbus Fritillariae Uninbracteatae bases total alkaloids.
This goal of the invention realizes by following technology: get the Chinese medicine extraction liquid that contains Bulbus Fritillariae Uninbracteatae bases total alkaloids, adjust pH value 1 to 7, filter, get filtrate and be added on the cation exchange resin column, earlier with the water elution remove impurity, reuse 0.5%～15% acid solution eluting, collect eluent, add the alkali neutralization,, promptly get Bulbus Fritillariae Uninbracteatae bases total alkaloids through desalting processing.
In above-mentioned technical process, after the extracting solution that will contain total alkaloids transfers to proper acidity, alkaloid ionization becomes cation, nonbasic substances is not ionized, after extracting solution was crossed cation exchange resin column, the hydrion on ionized alkaloid organic ion and the resin column exchanged and is adsorbed on the resin column securely.Here the pH value of extracting solution is unsuitable too high or too low, if too high, it is neutral or alkaline that extracting solution is, and alkaloid can not ionization, also just can not finish the exchange process on the resin; If cross lowly, the hydrogen ion concentration in the extracting solution is too high, has hindered the hydrion on the resin column and has dissociated, and can not finish the resins exchange process well equally, thereby the pH value of finding to adjust extracting solution in the experiment is 1 to 7 to be proper.During with water elution, use be deionized water, to guarantee not introducing new ion interference, those just are not easy to be got off by water elution by the nonbasic substances of resin absorption during eluting, thus be attracted to resin column on the alkaloid organic ion separated.After this acid solution that adds higher concentration is again carried out eluting, because the hydrogen ion concentration in the acid solution is very high at this moment, will combine with resin competitively, thereby the alkaloid organic ion that will be adsorbed on the resin column exchanges, be dissolved in the sour eluent, flow out resin column, finish alkaloidal enrichment process.Afterwards, in eluent, add alkali and neutralize unnecessary acid,, can obtain Bulbus Fritillariae Uninbracteatae bases total alkaloids that purity is higher again through conventional desalting processing.
This technical process compared with prior art, technological process is not simple, not with an organic solvent, residual, the alkaloid rate of transform height of no resin monomer composition; Its important contribution also is, has broken ion-exchange capacity order rule, that is: Ca that traditional theory is thought
2+＞K
+≈ NH
4 +＞Na
+＞H
+Just under the influence of this traditional theory, in the ionic exchange resin of Bulbus Fritillariae Uninbracteatae bases total alkaloids all is that alkali liquor or ammoniacal liquor carry out eluting, perhaps earlier with in the alkali liquor and the free in theory alkaloid of resin column reuse organic solvent reflux, extract,, and the effect in the practical application is very undesirable and be unsuitable for big production.In technical scheme of the present invention, though hydrionic exchange capacity is the most weak, but by improving hydrionic concentration in the sour eluent, thereby offset the weak shortcoming of its exchange capacity, simultaneously under acid condition, the alkaloid that exchanges is dissolved in the acid solution rapidly, and is rushed out pillar, guarantee alkaloidal elute effect thus.And, carry out eluting with acid solution, in eluting, cation exchange resin column is regenerated, thereby can recycle, reduced the process of regenerating resin post behind the alkali liquor eluting, reduced cost.Technology of the present invention has broken through in the prior art traditional view and the technical process with the alkali liquor eluting fully, obtained beyond thought effect, improved the yield of Bulbus Fritillariae Uninbracteatae bases total alkaloids greatly, making cation exchange resin be used for the refining Bulbus Fritillariae Uninbracteatae bases total alkaloids that separates in commercial production becomes possibility.
Based on above-mentioned technical process, the inventor has carried out further research again, and the parameter of each step of refinement filters out optimal case, and particular content is as follows:
1, the pH value scope of adjustment medicinal liquid is preferably 2 to 5 before the upper prop, and effect is more obvious.
2, used cation exchange resin can be macroporous type or gel-type strong acid ion exchange resin, can according to circumstances be processed in Hydrogen, sodium type or the ammonium type any when reality is used.
3, the post of used cation exchange resin column footpath there is no a fixed pattern with the ratio of post height, but considers to produce reality, post footpath: post height=1: 5～can obtain best effect at 1: 10 o'clock.
4, the liquor strength to sample on the resin column is that every ml is equivalent to crude drug 0.1～3g, and concrete condition can determine that if adopt modes such as dipping, percolation, the medicinal liquid that obtains will be rarer according to the pre-treatment mode of medicinal liquid; And if modes such as reflux, extract,, decoction are especially passed through concentration, the concentration of medicinal liquid will be bigger, but so long as in this scope, can both realize sample.Simultaneously, last sample speed is also adjusted according to the concentration of medicinal liquid in good time, satisfies substantially at 0.5～5 times of column volume/hour get final product.
5, go up sample loading mode and be typically chosen in from the post upper end upward sample, medicinal liquid flows through whole pillar by gravity flow power; The inventor finds, if sample on the adverse current, be about to medicinal liquid sample from the pillar bottom, by certain pressure, make medicinal liquid fill with whole pillar, thisly go up the maximum exchange efficient that sample loading mode can be brought into play pillar, when also having avoided from the upper end sample since the alkaloid exchange not exclusively take place shift to an earlier date penetration problem.This point also is the creationary discovery of inventor.
6, the used acid solution of eluting is preferably hydrochloric acid solution or sulfuric acid solution, and its concentration all is preferably 3%～6%.
7, the flow velocity of eluent is unsuitable too fast or slow excessively during eluting, if too fast, then the exchange of hydrion and alkaloid organic ion is insufficient, and acid solution is wasted more; If cross slowly, the alkaloid organic ion that then disintegrates down may adsorb back on the resin column again, influences elution efficiency.Experiment finds, elution speed remains on 2～6 times of column volumes/hour be advisable.Further preferred, elution speed remains on 4～6 times of column volumes/hour best.
8, the inventor also finds, improves elution efficiency if think more the highland, can not carry out the acid solution eluting immediately after the water elution remove impurity, but is full of acid solution earlier in resin column and leaves standstill more than 2 hours, generally need not surpass 12 hours, carry out eluting again.Through after leaving standstill, a large amount of alkaloid organic ions are exchanged by hydrion, perhaps are in half absorption, half dissociated state, and carry out eluting this moment, and the alkaloid concentration effect is obvious, and elution efficiency obviously improves.
9, in order further to improve elution efficiency, can also in the acid solution that eluting is used, add small amount of N H
4Cl, NaCl or CaCl
2, addition is unsuitable very few or too much, if very few, does not then have effect; If then easily saltouing because of salinity is too high influences the dissolubility of alkaloid organic ion too much.Experiment finds, in the eluent with NH
4 +, Na
+Or Ca
2+Be good when concentration is 0.1～1mol/L, further preferred, NH
4 +, Na
+Or Ca
2+Concentration best when being 0.1～0.3mol/L.
10, said desalination process can be the desalination method that dialysis desalination, membrane filtration are crossed desalination and other various medicine biological field routines in the technology, these methods comparative maturity all at present, and can channelization production.
11, in this method said Chinese medicine extraction liquid can be by dipping, percolation, ultrasonic, microwave or any mode in decocting extract and make, and the solvent that extracts can be in water, sour water, alcoholic solution, the acid ethanol solution any, but all belongs to the conventional extracting method of the present field of Chinese medicines.Distinctive points is, if make with dipping or percolation method, can directly go up sample; Obtain if extract, also will pass through steps such as precipitate with ethanol, filtration or centrifugal remove impurity, to guarantee the smooth of sample with additive method.
Need to prove that above-mentioned preferred technical parameter can carry out combination in any with basic technology according to the needs of practical situation, all can obtain good effect, the technical solution problem reaches purpose of the present invention.
Below by the contrast experiment advantage of the present invention is described.
One, experimental program:
Get Bulbus Fritillariae Thunbergii medical material 5000g, add 8 times of amounts of sour water of pH=3, soak a night, percolation is collected percolate to do not have a precipitation with the silico-tungstic acid inspection till, merges percolate, and is centrifugal, supernatant; Supernatant is five parts, carries out alkaloidal separation by following five kinds of methods respectively and purify:
(1) ion exchange resin+acid solution eluting: supernatant is regulated pH=3, on handled strong cation-exchanging resin 001 * 7 (Hydrogen well, blade diameter length ratio is 1: 8), last sample speed be 3 times of column volumes/hour, there is precipitation to stop to go up sample with the silico-tungstic acid inspection to effluent, it is colourless substantially that water is eluted to eluent, reuse 3% hydrochloric acid solution eluting, elution speed be 4 times of column volumes/hour the speed eluting, eluent has precipitation the time to begin to receive with the silico-tungstic acid inspection, receive eluent to do not have with the silico-tungstic acid inspection precipitation up to, merge eluent, be neutralized to neutrality with sodium hydroxide, desalination, drying gets the Bulbus Fritillariae Thunbergii total alkaloids.
(2) the acid solution eluting of ion exchange resin+salt: supernatant is regulated pH=3, on handled strong cation-exchanging resin 001 * 7 (Hydrogen well, blade diameter length ratio is 1: 8), last sample speed be 3 times of column volumes/hour, there is precipitation to stop to go up sample with the silico-tungstic acid inspection to effluent, water is not eluted to when eluent has color substantially and stops, and 0.5% hydrochloric acid solution of reuse 2% calcium chloride soaks resin.0.5% hydrochloric acid solution eluting of reuse 2% calcium chloride, elution speed be 4 times of column volumes/hour, eluent begins to receive when with the silico-tungstic acid inspection precipitation being arranged, receive eluent to do not have with the silico-tungstic acid inspection precipitation up to, merge eluent, be neutralized to about pH=7 desalination with calcium hydroxide, concentrate drying gets the Bulbus Fritillariae Thunbergii total alkaloids.
(3) ion exchange resin+reflux, extract: supernatant is regulated pH=3, on handled strong cation-exchanging resin 001 * 7 (Hydrogen, blade diameter length ratio are 1: 8) well, last sample speed be 3 times of column volumes/hour, there is precipitation to stop to go up sample with the silico-tungstic acid inspection to effluent, water is not eluted to when eluent has color substantially and stops eluting, and resin by pouring out in the post, is put in the porcelain dish and dried, it is an amount of to add 10% ammonia, stir, touched damp, be not advisable but do not touch with one's hand with hands.This resin is put in the apparatus,Soxhlet's,, chloroform solution is added anhydrous Na with chloroform reflux, extract, 2 hours
2SO
4After the dehydration, reclaim chloroform, the dry Bulbus Fritillariae Thunbergii total alkaloids that gets to the dried molassed pulpous state.
(4) macroporous adsorbent resin method: supernatant is regulated PH=10, on the DF01 type macroporous adsorbent resin handled well, last sample speed be 4 times of column volumes/hour, have precipitation to stop to go up sample with the silico-tungstic acid inspection to effluent, water is eluted to and stops eluting when eluent does not have color substantially.With alcohol-water (70: 30) is eluant, with 2.5 times of column volumes/hour speed carry out eluting, eluent has precipitation the time to begin to receive with the silico-tungstic acid inspection, receive eluent to do not have with the silico-tungstic acid inspection precipitation up to, merge eluent, reclaim ethanol, drying gets the Bulbus Fritillariae Thunbergii total alkaloids.
(5) organic solvent extractionprocess: supernatant is regulated PH=10, divide three extractions with 10 times of amount chloroforms earlier, 10 times of amounts of reuse ethyl acetate extraction three times merges all extracts, and evaporate to dryness gets the Bulbus Fritillariae Thunbergii total alkaloids.
Two, the result calculates: distinguish the weight of five kinds of technology gained of weighing total alkaloids, and be divided by with the medical material amount, get the yield of total alkaloids; Adopt the quantitative approach of acid base titration respectively, five kinds of method gained total alkaloidss are carried out assay, calculate the purity of total alkaloids.
Three, result's contrast, see the following form:
The effect assessment table of five kinds of technologies
By above comparing result as seen, technical scheme of the present invention can solve deficiency of the prior art, and improve significantly product quality, reduce cost, improve safety and producing feasibility, the present invention has reached goal of the invention.
Technical scheme of the present invention is suitable for the refining purification of Bulbus Fritillariae Uninbracteatae bases total alkaloids effective site.Bulbus Fritillariae Cirrhosae records in 2005 editions one one 141 pages of Chinese Pharmacopoeia pharmacopeia, is the dry bulb of Liliaceae (Liliaceae) Bulbus Fritillariae Cirrhosae Fritillaria cirrhosa D.Don, dark violet Bulbus Fritillariae Uninbracteatae Fritillaria unibracteata Hsiao et K.C.Hsia, Gansu Bulbus Fritillariae Uninbracteatae Fritillaria przewalskiiMaxim. or Bulbus Fritillariae cirrhosae Fritillaria delavayi Ftanch..Former three is practised title " loose shellfish " and " blue or green shellfish " respectively by the character difference, and the latter practises title " lubei ", has effects such as clearing heat and moistening lung, preventing phlegm from forming and stopping coughing.Bulbus Fritillariae Thunbergii is the dry bulb of Liliaceae Fritillaria plant Bulbus Fritillariae Thunbergii Fritillatia thunbergii Miq., has effects such as heat clearing away eliminating stagnation, preventing phlegm from forming and stopping coughing.Bulbus Fritillariae Ussuriensis records in 2005 editions one one 65 pages of Chinese Pharmacopoeia pharmacopeia, is the dry bulb of liliaceous plant Bulbus Fritillariae Ussuriensis Fritillariaussuriensis Maxim., effects such as tool clearing heat and moistening lung, preventing phlegm from forming and stopping coughing.Bulbus Fritillariae Pallidiflorae is the dry bulb of liliaceous plant Fritillaria walujewii Regel Fritillaria walujewii Regel or Fritillaria pallidiflora Schrenk Fritillaria palli diflora Schrenk, has effects such as clearing heat and moistening lung, preventing phlegm from forming and stopping coughing.Hupeh Fritillary Bulb records in 2005 editions one one 242 pages of Chinese Pharmacopoeia pharmacopeia, and the dry bulb of liliaceous plant Hupeh Fritillary Bulb Fritillaria hupehensis Hsiao et K.C.Hsia has the effect of removing heat-phlegm, cough-relieving, eliminating stagnation.Above-mentioned five kinds of medical materials all derive from Liliaceae, and contained chemical constituent is also substantially the same, and mostly is steroid alkaloid.Studies show that, their total alkaloidss separately are its main effective site, comprise that Bulbus Fritillariae Uninbracteatae third element (Fritimine), Min shellfish alkali (Minpeimine), the Min shellfish in the Bulbus Fritillariae Cirrhosae divided alkali (Minpeiminine), chinpeimine (Chinpeimine), lu pei alkali (Fritiminine) etc.; Peimine in the Bulbus Fritillariae Thunbergii (peimine, peimine, verticine), peiminine (peiminine, peimi-nine, verticinone), (-)-Zhebeinine (zhebeinine), zhebeirine (zheberine), Bulbus Fritillariae Thunbergii ketone (zhebeinone) etc.; Imperialine in the Bulbus Fritillariae Ussuriensis (sipeimine) etc.; Imperialine in the Bulbus Fritillariae Pallidiflorae (sipeimine) etc.; Hubei first element (peimine) in the Hupeh Fritillary Bulb, Hubei second element (peiminine), Hupeh Fritillary Bulb first element (hupehenine), hupehenirine alkaloid components such as (hupehenirine).Clinical Bulbus Fritillariae Uninbracteatae bases total alkaloids preparation has been used for the treatment of cough with asthma etc., has shown good curative effect.Confirm through a large amount of tests, the technology of cation exchange resin sour water eluting Bulbus Fritillariae Uninbracteatae bases total alkaloids, have that cost is low, organic solvent consumption less, the selectivity height, total alkaloids purity is high and help realizing advantage such as the big production of industry, for a brand-new platform has been created in the R﹠D and production of Chinese medicine Bulbus Fritillariae Uninbracteatae bases total alkaloids preparation.
The specific embodiment
Embodiment 1:
Get Bulbus Fritillariae Cirrhosae decoction pieces 1000g, decoct with water 2 times, each 10 times of amounts decocted 2 hours, merged decoction liquor, centrifugal, regulate pH=3, centrifugal, supernatant is with 4 times of column volumes/hour by cation exchange resin (001 * 7, Hydrogen, blade diameter length ratio 1: 8), being washed to effluent does not have color, adds 3% sulphuric acid eluting, elution speed be 2 times of column volumes/hour, collect eluent, check negative (effluent drips 10% silico-tungstic acid does not have precipitation), be neutralized to neutrality with sodium hydroxide to alkaloid, desalination, the filtrate concentrate drying gets the Bulbus Fritillariae Cirrhosae total alkaloids.
Embodiment 2:
Get Bulbus Fritillariae Cirrhosae decoction pieces 1000g, the sour water percolation that adds pH=5, merge the percolate thin up to 10000ml, centrifugal, regulate pH=1, centrifugal, supernatant is with 5 times of column volumes/hour by cation exchange resin (001 * 12, the sodium type, blade diameter length ratio 1: 5), being washed to effluent does not have color, reuse 0.5% hydrochloric acid solution eluting, elution speed be 4 times of column volumes/hour, soaked behind 2 times of column volumes of eluting 5 hours, be eluted to alkaloid again and check negative (effluent drips 10% silico-tungstic acid does not have precipitation), collect this part eluent, be neutralized to neutrality with calcium hydroxide, desalination, the filtrate concentrate drying gets the Bulbus Fritillariae Cirrhosae total alkaloids.
Embodiment 3:
Get Bulbus Fritillariae Cirrhosae decoction pieces 5kg, add 70% ethanol ultrasonic extraction twice, add 5 times of amounts at every turn, ultrasonic 0.5 hour, merge extractive liquid,, centrifugal, reclaim ethanol, add water to 5000ml, regulate pH=2, centrifugal, supernatant is with 2 times of column volumes/hour by last cation exchange resin (001 * 10, sodium type, blade diameter length ratio 1: 7), being washed to effluent does not have color, the hydrochloric acid solution of the reuse 6% (CaCl that contains 1mol/L
2) eluting, elution speed be 5 times of column volumes/hour, collect eluent, check negative (effluent drips 10% silico-tungstic acid does not have precipitation) to alkaloid, be neutralized to neutrality with sodium hydroxide, desalination, the filtrate concentrate drying gets the Bulbus Fritillariae Cirrhosae total alkaloids.
Embodiment 4:
Get Bulbus Fritillariae Thunbergii decoction pieces 10kg, decoct with water 2 times, each 10 times of amounts decocted 2 hours, merge decoction liquor, filter, it is 1.1 (60 ℃) that filtrate is concentrated into relative density, and adding ethanol to concentration is 70%, leave standstill, supernatant reclaims ethanol, adds water to 3000ml, regulates pH=4, centrifugal, supernatant is with 3 times of column volumes/hour by last cation exchange resin (011 * 6, ammonia type, blade diameter length ratio 1: 9), be washed to effluent and do not have color, reuse 15% sulfuric acid solution eluting, elution speed be 6 times of column volumes/hour, collect eluent, to alkaloid inspection negative (effluent drips 10% silico-tungstic acid does not have precipitation), be neutralized to neutrality with sodium hydroxide, desalination, the filtrate concentrate drying gets the Bulbus Fritillariae Thunbergii total alkaloids.
Embodiment 5:
Bulbus Fritillariae Uninbracteatae decoction pieces 10kg makes even, decoct with water 2 times, each 10 times of amounts decocted 2 hours, merge decoction liquor, filter, it is 1.1 (60 ℃) that filtrate is concentrated into relative density, and adding ethanol to concentration is 70%, leave standstill, supernatant reclaims ethanol, adds water to 5000ml, regulates pH=5, centrifugal, supernatant is with 3 times of column volumes/hour by last cation exchange resin (D001 * 4, Hydrogen, blade diameter length ratio 1: 10), be washed to effluent and do not have color, reuse 3% hydrochloric acid solution eluting, elution speed be 3 times of column volumes/hour, collect eluent, to alkaloid inspection negative (effluent drips 10% silico-tungstic acid does not have precipitation), be neutralized to neutrality with sodium hydroxide, desalination, the filtrate concentrate drying gets the Bulbus Fritillariae Ussuriensis total alkaloids.
Embodiment 6:
Get Bulbus Fritillariae Pallidiflorae decoction pieces 10kg, decoct with water 2 times, each 10 times of amounts decocted 2 hours, merge decoction liquor, filter, it is 1.1 (60 ℃) that filtrate is concentrated into relative density, and adding ethanol to concentration is 70%, leave standstill, supernatant reclaims ethanol, adds water to 4000ml, regulates pH=4, centrifugal, supernatant is with 0.5 times of column volume/hour by last cation exchange resin (001 * 18, Hydrogen, blade diameter length ratio 1: 6), be washed to effluent and do not have color, reuse 0.5% sulfuric acid solution (sodium chloride that contains 0.1mol/L) eluting, elution speed be 5 times of column volumes/hour, collect eluent, to alkaloid inspection negative (effluent drips 10% silico-tungstic acid does not have precipitation), be neutralized to neutrality with sodium hydroxide, desalination, the filtrate concentrate drying gets the Bulbus Fritillariae Pallidiflorae total alkaloids.
Embodiment 7:
Get Hupeh Fritillary Bulb decoction pieces 10kg, decoct with water 2 times, each 10 times of amounts decocted 2 hours, merge decoction liquor, filter, it is 1.1 (60 ℃) that filtrate is concentrated into relative density, and adding ethanol to concentration is 70%, leave standstill, supernatant reclaims ethanol, adds water to 10000ml, regulates pH=3, centrifugal, supernatant is with 3 times of column volumes/hour by last cation exchange resin (001 * 5, Hydrogen, blade diameter length ratio 1: 8), be washed to effluent and do not have color, reuse 15% hydrochloric acid solution (calcium chloride that contains 0.3mol/L) eluting, elution speed be 6 times of column volumes/hour, collect eluent, to alkaloid inspection negative (effluent drips 10% silico-tungstic acid does not have precipitation), be neutralized to neutrality with sodium hydroxide, desalination, the filtrate concentrate drying gets the Hupeh Fritillary Bulb total alkaloids.
Embodiment 8:
Get Bulbus Fritillariae Cirrhosae decoction pieces 1000g, decoct with water 2 times, each 10 times of amounts decocted 2 hours, merge decoction liquor, filter, it is 1.1 (60 ℃) that filtrate is concentrated into relative density, and adding ethanol to concentration is 70%, leave standstill, supernatant reclaims ethanol, adds water to 1000ml, regulates pH=3, centrifugal, supernatant is with 3 times of column volumes/hour by last cation exchange resin (001 * 5, Hydrogen, blade diameter length ratio 1: 8), be washed to effluent and do not have color, reuse 6% sulfuric acid solution eluting, elution speed be 4 times of column volumes/hour, collect eluent, to alkaloid inspection negative (effluent drips 10% silico-tungstic acid does not have precipitation), be neutralized to neutrality with sodium hydroxide, desalination, the filtrate concentrate drying gets the Bulbus Fritillariae Cirrhosae total alkaloids.
Embodiment 9:
Get Bulbus Fritillariae Thunbergii decoction pieces 2000g, the hydrochloric acid solution that adds pH=3, microwave extraction 2 times adds 5 times of volume microwave extractioies 0.5 hour at every turn, filters, the filtrate thin up is to 1600ml, regulate pH=6, centrifugal, supernatant is with 2 times of column volumes/hour by last cation exchange resin (001 * 15, Hydrogen, blade diameter length ratio 1: 6), being washed to effluent does not have color, reuse 5% hydrochloric acid solution (ammonia chloride that contains 0.2mol/L) eluting, elution speed be 5 times of column volumes/hour, collect eluent, check negative (effluent drips 10% silico-tungstic acid does not have precipitation), be neutralized to neutrality with sodium hydroxide to alkaloid, desalination, the filtrate concentrate drying gets the Bulbus Fritillariae Thunbergii total alkaloids.
Embodiment 10:
Get Hupeh Fritillary Bulb decoction pieces 5kg, add twice of 70% ethanol ultrasonic extraction, add 5 times of amounts at every turn, ultrasonic 0.5 hour, merge extractive liquid,, centrifugal, reclaim ethanol, add water to 5000ml, regulate pH=7, centrifugal, supernatant is so that 2 times of column volumes/hour by last large pores cation exchange resin, being washed to effluent does not have color, the sulfuric acid solution of reuse 4% (ammonia chloride of 0.6mol/L) eluting, elution speed be 5 times of column volumes/hour, collect eluent, check negative (effluent drips 10% silico-tungstic acid does not have precipitation), be neutralized to neutrality with sodium hydroxide to alkaloid, desalination, the filtrate concentrate drying gets the Hupeh Fritillary Bulb total alkaloids.
Embodiment 11:
Get Bulbus Fritillariae Pallidiflorae decoction pieces 5kg, decoct with water 2 times, each 10 times of amounts decocted 1 hour, merge decoction liquor, filter, it is 1.05 (60 ℃) that filtrate is concentrated into relative density, and adding ethanol to concentration is 80%, leave standstill, supernatant reclaims ethanol, adds water to 2000ml, regulates pH=4, centrifugal, supernatant is with 4 times of column volumes/hour by last cation exchange resin (D001 * 7, sodium type, blade diameter length ratio 1: 7), be washed to effluent and do not have color, reuse 3% hydrochloric acid solution eluting, elution speed be 3 times of column volumes/hour, collect eluent, to alkaloid inspection negative (effluent drips 10% silico-tungstic acid does not have precipitation), be neutralized to neutrality with sodium hydroxide, desalination, the filtrate concentrate drying gets the Bulbus Fritillariae Pallidiflorae total alkaloids.
Claims (13)
1, a kind of method of from Chinese medicine extraction liquid, separating Bulbus Fritillariae Uninbracteatae bases total alkaloids, it is characterized in that this method is: get the Chinese medicine extraction liquid that contains Bulbus Fritillariae Uninbracteatae bases total alkaloids, adjust pH value 1 to 7, be added on the cation exchange resin column, earlier with the water elution remove impurity, reuse 0.5%～15% acid solution eluting, collect eluent, add the alkali neutralization,, promptly get Bulbus Fritillariae Uninbracteatae bases total alkaloids through desalting processing.
2, the method for separation Bulbus Fritillariae Uninbracteatae bases total alkaloids as claimed in claim 1 is characterized in that the preceding pH value scope of adjusting medicinal liquid of upper prop is 2 to 5.
3, the method for separation Bulbus Fritillariae Uninbracteatae bases total alkaloids as claimed in claim 1 is characterized in that used cation exchange resin can be macroporous type or gel-type strong acid ion exchange resin.
4, the method for separation as claimed in claim 3 Bulbus Fritillariae Uninbracteatae bases total alkaloids is characterized in that the post footpath of used cation exchange resin column: post height=1: 5～1: 10.
5, the method for separation as claimed in claim 1 Bulbus Fritillariae Uninbracteatae bases total alkaloids, the concentration that it is characterized in that going up in this method the sample medicinal liquid is that every ml is equivalent to crude drug 0.1～3g, last sample speed be 0.5～5 times of column volume/hour.
6, the method for separation Bulbus Fritillariae Uninbracteatae bases total alkaloids as claimed in claim 5 is characterized in that sample loading mode is preferably sample on the adverse current.
7, the method for separation as claimed in claim 1 Bulbus Fritillariae Uninbracteatae bases total alkaloids is characterized in that eluting is used in this method acid solution is 3%～6% hydrochloric acid solution or 3%～6% sulfuric acid solution.
8, the method for separation as claimed in claim 7 Bulbus Fritillariae Uninbracteatae bases total alkaloids, it is characterized in that elution speed be 2～6 times of column volumes/hour.
9, the method for separation as claimed in claim 8 Bulbus Fritillariae Uninbracteatae bases total alkaloids, it is characterized in that elution speed be 4～6 times of column volumes/hour.
10, the method for separation as claimed in claim 1 Bulbus Fritillariae Uninbracteatae bases total alkaloids is characterized in that after the water elution remove impurity, can be full of eluting earlier with acid solution and left standstill 2～12 hours in resin column, carries out eluting again.
11, the method for separation as claimed in claim 7 Bulbus Fritillariae Uninbracteatae bases total alkaloids is characterized in that can also adding in the acid solution that eluting uses the NH of 0.1～1mol/L
4Cl, NaCl or CaCl
2
12, the method for separation Bulbus Fritillariae Uninbracteatae bases total alkaloids as claimed in claim 11 is characterized in that the concentration of salt is preferably 0.1～0.3mol/L in the acid solution.
13, the Bulbus Fritillariae Uninbracteatae bases total alkaloids of any one described method preparation among the claim 1-12.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007100984424A CN101491631A (en) | 2007-04-18 | 2007-04-18 | Method for separating verticine total alkaloids in traditional Chinese medicine extract |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007100984424A CN101491631A (en) | 2007-04-18 | 2007-04-18 | Method for separating verticine total alkaloids in traditional Chinese medicine extract |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105770375A (en) * | 2016-04-15 | 2016-07-20 | 中国科学院新疆理化技术研究所 | Preparing method and application of fritillaria pallidiflora extract |
| CN111018698A (en) * | 2019-12-25 | 2020-04-17 | 新疆维吾尔自治区中药民族药研究所 | Monomer compound separated from Fritillaria pallidiflora extract and preparation method and application thereof |
| CN114720576A (en) * | 2021-01-05 | 2022-07-08 | 中国科学院大连化学物理研究所 | Method for enriching and purifying steroid alkaloid in fritillaria medicinal material |
-
2007
- 2007-04-18 CN CNA2007100984424A patent/CN101491631A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105770375A (en) * | 2016-04-15 | 2016-07-20 | 中国科学院新疆理化技术研究所 | Preparing method and application of fritillaria pallidiflora extract |
| CN111018698A (en) * | 2019-12-25 | 2020-04-17 | 新疆维吾尔自治区中药民族药研究所 | Monomer compound separated from Fritillaria pallidiflora extract and preparation method and application thereof |
| CN114720576A (en) * | 2021-01-05 | 2022-07-08 | 中国科学院大连化学物理研究所 | Method for enriching and purifying steroid alkaloid in fritillaria medicinal material |
| CN114720576B (en) * | 2021-01-05 | 2024-01-23 | 中国科学院大连化学物理研究所 | Method for enriching and purifying steroid alkaloids in fritillaria medicinal materials |
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Open date: 20090729 |