CN1295230C - Production of high-purity glabrene - Google Patents
Production of high-purity glabrene Download PDFInfo
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- CN1295230C CN1295230C CNB2005100238608A CN200510023860A CN1295230C CN 1295230 C CN1295230 C CN 1295230C CN B2005100238608 A CNB2005100238608 A CN B2005100238608A CN 200510023860 A CN200510023860 A CN 200510023860A CN 1295230 C CN1295230 C CN 1295230C
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Abstract
The present invention relates to a producing method for high-purity glabridin. Glycyrrhiza glabra is leached by water or is extracted without water, and is extracted by organic solvent or is extracted and concentrated by a back flow. An obtained concentrated substance or the glabridin with the purity at most 40% is ultrafiltered by an ultrafiltration membrane or is directly absorbed by high-molecular resin without ultrafiltration, and is eluted by water, ethanol and acetone or the mixed liquids of the water, the ethanol and the acetone so as to be concentrated, dissolved and recrystallized. All of used solvent, adsorbing agents and eluting liquid can be recycled. The present invention is an industrialized recycle type production technology with low cost.
Description
Technical field:
The present invention relates to the scale production process of separation and purification acquisition high purity (＞90%) glabridin (Glabridin) from glycyrrhiza glabra (Glycyrrhiza glabra linne) extracting solution.
Background technology:
Glabridin now proved a kind of extremely effectively and the natural whiting agent that has no side effect, extensively be applied the clear 62-29528 of JP at present in the makeup field of whitening; JP2-204495 has reported and extracted the method that contains glabridin from glycyrrhiza glabra.JP1-311011; USP5609875 has narrated prescription and method that Glabridin uses as whitening agent.Yet, because its content in glycyrrhiza glabra only is about 2/1000ths, therefore it is very complicated to obtain highly purified glabridin formality, the cost costliness also can only be glabridin mixture solution or the colored powder shape glabridin mixture that content differs as employed glabridin whitening agent in the market.
For example: Japanese ball is apt to company (Maruzen pharma CO., glabridin commodity PT-10 LTD); PT-20; PT-40 is and respectively contains glabridin 10%; 20%; 40% Huang～henna powder.
Yet discover that glabridin is anti-oxidant except having owing to deepen continuously in recent years, restrain outside the melanochrome effect also have functions such as anti-lipid, anti-mastocarcinoma, prevention atherosclerosis.
As document Cancer cell cacel res, octoterl, 2000; 60 (20) 5704～5709 report glabridins can suppress the propagation of breast cancer cell, and has a function of plant female hormone, can remedy the estrogen deficiency of climacteric women in good time, thereby restrain women's estrogen deficiencies such as breast cancer that shape is risen owing to lacking oestrogenic hormon.And for example document Original Research Communication 66 (2) 267 report glabridins can be restrained the peroxidation (Peroxidation) of low-density lipoprotein (Low-density lipoprotein) thereby stop generation shape to play artery hardened congee sample peroxidation low-density lipoprotein.
Moreover, because impure glabridin mixture has color and luster,,, the demand of colourless high-purity glabrene just will inevitably be proposed with respect to white in the past whitening product for high-level customer base.
Therefore, from development trend, just must develop the production technique of energy large-scale production high purity, low cost optical licoricidin.And the method cost that bibliographical information is in the past produced the pure product of glabridin is all very expensive, narrated the operation of a purifying glabridin as document Journal of natural products vol 43 No 2 P259～269 (1980), this method direct solvent extraction, after this adopt the silicic acid column chromatography, use chloroform-methanol as moving phase, the silicic acid that consumes is that per 600 grams can only be produced 1 gram glabridin, has also consumed several kilograms unrenewable mixed solvent.
And for example document JP 6-157277 has narrated the method for a purifying high-purity glabridin, this method adopts silica gel column chromatography, what it adopted is through the secondary silica gel column chromatography, for the first time make moving phase for forward silica gel column chromatography (use chloroform-methanol), the gained crude product carries out the reverse silica gel column chromatography second time, makes water-acetone make moving phase, recrystallization gets the elaboration glabridin at low temperatures at last, 1 gram glabridin is wished to get in measuring and calculating, consumes silica gel 474 grams, and a large amount of unrenewable mixed solvents.
Method has all consumed a large amount of sorbent materials and great toxicity organic solvent on this, operates also complicatedly unusually, and the costliness of cost has limited it and entered commodity market.Though because the activity of whitening of glabridin than in the past much higher as arbutin, vitamin C derivatives, kojic acid etc., but its active threshold values also will be in 5/10000ths～millesimal concentration, i.e. 500～1000ppm level, this is still more much higher than some biologically active substance such as EGF (1ppm level) etc., as is used for oral as phytoestrogen or restrain atherosclerosis then requirement is bigger.
Summary of the invention:
In order to overcome aforementioned disadvantages, the object of the invention provides a kind of production method that obtains high-purity glabrene from glycyrrhiza glabra.This method be a kind of cheaply, can industrialized production method.
The present invention adopts the extraction process of optimization and uses the purifying process of optimizing, use repeatably macromolecule resin, with nontoxic recyclable solvents such as water, alcohol, carry out drip washing, obtain the glabridin crude product through once slightly adsorbing drip washing again, need not cryogenic conventional recrystallization and just can obtain purity through once easy again greater than the glabridin more than 90%.
The extraction flow process of being taked in the extraction process that the present invention taked is to comprise: 1. pulverize back Radix Glycyrrhizae drying, make moisture content less than 2%, then with the direct extracting of solvent, the technical process of repurity; 2. pulverize not drying of back Radix Glycyrrhizae, moisture content directly extracts the flow process of back purifying then greater than 5% with solvent; 3. pulverize the back Radix Glycyrrhizae with 50～80 ℃ of water rettings 2～20 hours or water refluxing extraction after 2～20 hours, residue is with centrifugal or squeezing or dry to moisture content residually less than 5%～20%, carries out the flow process of purifying after the solvent extraction again.
Purifying process used in the present invention to remove a large amount of polymer foreign pigments, carries out further macromolecule resin absorption, leacheate drip washing and recrystallizing and refining for 1. extracting solution is concentrated through ultrafiltration again; 2. directly carry out macromolecule resin absorption, leacheate drip washing and recrystallization without ultrafiltration.
Production method of the present invention, be with commercially available content for≤40% glabridin or with glycyrrhiza glabra through or without water extraction or extraction, organic solvent extraction or refluxing extraction, be concentrated into and be bordering on gained glabridin crude product, with ultra-filtration membrane ultrafiltration, concentrated, adsorb with macromolecule resin again, water, ethanol, propyl alcohol or their mixing solutions drip washing then, drip washing, concentrated solvent recrystallization with one or more.
Macromolecule resin used in the present invention comprises large aperture adsorption resin (styrene type), polyacrylamide or polyamide resin etc., and employed cleaning solvent is water, ethanol, acetone or propyl alcohol etc.
Recrystallization solvent used in the present invention is acetone, ethanol, ethyl acetate, benzene, toluene, isopropyl ether or chloroform and their mixture.Especially acetone, ethanol, ethyl acetate or isopropyl ether, and their mixture.
Extraction solvent in the extraction process of the present invention is 95% ethanol, dehydrated alcohol, acetone, normal hexane, vinyl acetic monomer, solvent oil or sherwood oil equal solvent.
Ultra-filtration membrane of the present invention aperture is 1000～10000 molecular weight cut-offs.Adopt method of the present invention can obtain the glabridin of purity＞90%, not only method easy, with low cost, be fit to suitability for industrialized production, and the glabridin that obtains is a white products, good stability, its propylene glycol solution colourity of 1% only is 50 (APHA standards), and heats to 50 ℃ and keep half an hour, colourity remains unchanged, the cream frost that its thousandth concentration is made is placed also nondiscoloration in two months at 40 ℃, still is white.
Description of drawings:
Fig. 1 is the glabridin high-pressure liquid phase spectrogram that the inventive method is produced.
Wherein ordinate is a Wavelength strength, and abscissa is time (branch).
Embodiment:
Embodiment 1.
Water content 6%200kg is got in the glycyrrhiza glabra pulverizing to be thrown in the extraction pot, with 1000kg dehydrated alcohol reflux extraction 8 hours, get the extraction liquid extracting solution and carry out ultrafiltration (membrane pore size is 10,000 molecular weight), filtrate concentrates, get 11.8kg medicinal extract, water, Diluted Alcohol washing successively after adsorbing with 100kg wide aperture styrene resin, 1.28kg glabridin crude product, again through recrystallization (ethanol-isopropyl ether is a refining solvent) 346 gram purity greater than 90% pure product of glabridin.
Get 200kg moisture content and be 2% pulverizing glycyrrhiza glabra, with 1000kg dehydrated alcohol extraction 8 hours, extraction liquid is concentrated into dried, get 7.6kg medicinal extract, get 1.31kg glabridin crude product with 100kg polymeric amide water successively and different ratios solvent (ethanol, acetone etc.) washing and filtering, get 359 gram purity greater than 90% pure product of glycyrrhiza glabra through recrystallization again.
Embodiment 3.
Get 200kg moisture and be glycyrrhiza glabra after 8% the pulverizing, with 1000kg flooding (50～80 ℃) 24 hours, the centrifugal most of moisture of removing was carried out extracting 5 hours with the 1000kg ethyl acetate again, extraction liquid concentrate 5.9kg medicinal extract.Water, solvent (ethanol or acetone) flushing successively after adsorbing with 100kg wide aperture resin (the same specification), 1.08kg glabridin crude product, again through isopropyl ether-acetone refining, 380 gram purity greater than 90% pure product of glabridin.
Embodiment 4.
Get 200kg moisture and be glycyrrhiza glabra after 8% the pulverizing, with 2000kg hydroecium temperature lixiviate 24 hours, the centrifugal most of moisture of removing was carried out extracting 8 hours with the 1000kg ethyl acetate again, extraction liquid concentrate 6.8kg medicinal extract.Water, solvent (ethanol or acetone) flushing successively after adsorbing with 100kg wide aperture resin, 1.21kg glabridin crude product, again through isopropyl ether-acetone recrystallization, 358 gram purity greater than 90% pure product of glabridin.
Embodiment 5.
Get 200kg moisture content and be glycyrrhiza glabra after 2% the pulverizing, carried out extracting 8 hours with the 1000kg ethyl acetate, extraction liquid is through ultrafiltration (membrane pore size is 4000 molecular weight), through concentrate the Powdered light brown solid of 5.2kg, water, rare acetone rinsing successively after adsorbing with 100kg wide aperture resin (the same specification), 1.32kg glabridin crude product, again through acetone refining, 420 gram purity greater than 90% pure product of glabridin.
Get the pure product of the above-mentioned glabridin of 100mg and be dissolved in the 10ml propylene glycol, the colour examining degree is 50 (APHA), places 30 minutes at 50 ℃ then, surveys its colourity again, and its APHA still is 50.
With millesimal concentration, make the cream frost, placed nondiscoloration 2 months down for 40 ℃ at constant temperature.
Embodiment 6.
Get 200kg moisture content and be 2% pulverizing glycyrrhiza glabra, carried out extracting 8 hours with the 1000kg ethyl acetate, through concentrate 6.98kg, be adsorbed on the macroporous resin column of using after 8 times, then with water, Diluted Alcohol drip washing, leacheate concentrates, through recrystallization, 368 grams to measure purity through HPLC be 97.28% glabridin.(HPLC) records spectrogram as shown in Figure 1 through high pressure liquid chromatography.
The HPLC condition:
Stationary phase: Elipse XDB-C
8Post
Moving phase: acetonitrile: 2% acetate=1: 1
Detect wavelength: 282nm
Flow velocity: 1.8ml/min
Concentration: 1mg/1ml ethanol
Sample size: 5 μ l
t
R＝3.795min
Content=97.287960%.
Claims (5)
1, a kind of production method of high-purity glabrene, with the glycyrrhiza glabra warp or without water extraction, with organic solvent extraction or refluxing extraction, concentrated, it is characterized in that enriched material is through the ultra-filtration membrane ultrafiltration, concentrated, macromolecule resin absorption, water, ethanol, acetone or their mixed solution drip washing then, the drip washing thing is with one or more organic solvent recrystallization.
2, the production method of high-purity glabrene according to claim 1 is characterized in that described ultra-filtration membrane aperture is 1000～10000 molecular weight cut-offs.
3, the production method of high-purity glabrene according to claim 1 is characterized in that described glycyrrhiza glabra and macromolecule resin weight ratio are 1: 2～15.
4, the production method of high-purity glabrene according to claim 1 is characterized in that described macromolecule resin is nonpolar macroporous footpath resin, polymeric amide or polyacrylamide.
5, the production method of high-purity glabrene according to claim 1 is characterized in that described recrystallization organic solvent is acetone, ethanol, ethyl acetate, benzene, toluene, isopropyl ether, chloroform or their mixed solvent.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100238608A CN1295230C (en) | 2005-02-05 | 2005-02-05 | Production of high-purity glabrene |
| JP2006028918A JP4675248B2 (en) | 2005-02-05 | 2006-02-06 | Production method of high purity Glabridin |
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2005100238608A CN1295230C (en) | 2005-02-05 | 2005-02-05 | Production of high-purity glabrene |
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| CN1680386A CN1680386A (en) | 2005-10-12 |
| CN1295230C true CN1295230C (en) | 2007-01-17 |
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| CNB2005100238608A Active CN1295230C (en) | 2005-02-05 | 2005-02-05 | Production of high-purity glabrene |
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| JP (1) | JP4675248B2 (en) |
| CN (1) | CN1295230C (en) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101519408B (en) * | 2008-02-27 | 2012-08-29 | 新疆富沃药业有限公司 | Method for producing glabridin from glycyrrhiza residue |
| CN101735233B (en) * | 2009-12-11 | 2011-11-16 | 暨南大学 | Method for producing high-purity glabridin |
| CN101830906B (en) * | 2009-12-13 | 2012-06-27 | 成都普思生物科技有限公司 | Separation and purification method of high-purity glabridin |
| CN103848841B (en) * | 2012-11-29 | 2016-01-20 | 陕西华泰生物精细化工有限公司 | Employ new technology from licorice slag, extract the method for high-purity glabrene |
| CN104277048B (en) * | 2013-07-10 | 2016-09-21 | 岳普湖天瑞生物工程有限公司 | A kind of preparation method of Glycyrrhiza glabra L. total flavones |
| CN103360404B (en) * | 2013-07-30 | 2015-10-14 | 天津尚美化妆品有限公司 | A kind of method extracting high-purity glabrene from glycyrrhiza glabra |
| CN103923094A (en) * | 2014-04-14 | 2014-07-16 | 石河子大学 | Method for separating active component-glabridin contained in natural product glycyrrhiza glabra |
| CN105294722B (en) * | 2014-06-26 | 2017-12-05 | 湖北阿泰克糖化学有限公司 | A kind of preparation method of high-purity glabrene monomer |
| CN104072512B (en) * | 2014-07-21 | 2016-08-24 | 江苏天晟药业有限公司 | A kind of preparation method of glabridin |
| CN104725394A (en) * | 2015-03-02 | 2015-06-24 | 李玉山 | Method for preparing glabridin |
| CN104983602A (en) * | 2015-08-11 | 2015-10-21 | 上海奥利实业有限公司 | Whitening agent combining water-soluble glabridin and endothelin antagonist |
| CN110922413A (en) * | 2019-12-10 | 2020-03-27 | 辰风天然本草(北京)科技有限公司 | Extraction and separation method of glabridin |
| CN111187317A (en) * | 2020-02-19 | 2020-05-22 | 洛阳蓝斯利科技有限公司 | Preparation method of glycosidation glabridin |
| CN113754676B (en) * | 2021-09-17 | 2022-11-25 | 西安绿天生物技术有限公司 | Preparation method of water-soluble glabridin with high bioavailability |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6157277B2 (en) * | 1980-03-26 | 1986-12-05 | Hitachi Ltd |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP3084090B2 (en) | 1991-06-04 | 2000-09-04 | 丸善製薬株式会社 | Antiplasmin agent |
| JP3091045B2 (en) * | 1993-03-04 | 2000-09-25 | 丸善製薬株式会社 | Skin cosmetics |
| CN1203068C (en) * | 2003-07-11 | 2005-05-25 | 上海奥利实业有限公司 | Extraction and purification method of licoflavone |
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- 2005-02-05 CN CNB2005100238608A patent/CN1295230C/en active Active
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JPS6157277B2 (en) * | 1980-03-26 | 1986-12-05 | Hitachi Ltd |
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| Publication number | Publication date |
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| CN1680386A (en) | 2005-10-12 |
| JP2006213722A (en) | 2006-08-17 |
| JP4675248B2 (en) | 2011-04-20 |
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