CN1724552A - Preparation method of astilbin - Google Patents

Preparation method of astilbin Download PDF

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Publication number
CN1724552A
CN1724552A CN200510040944.2A CN200510040944A CN1724552A CN 1724552 A CN1724552 A CN 1724552A CN 200510040944 A CN200510040944 A CN 200510040944A CN 1724552 A CN1724552 A CN 1724552A
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astilbin
preparation
ethanol
weight
recrystallization
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CN100348606C (en
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陈婷
姚毅
徐强
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Nanjing University
Chia Tai Tianqing Pharmaceutical Group Co Ltd
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Nanjing University
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Abstract

The invention provides a process for preparing astilbin which comprises the steps of disintegrating medicinal materials, extracting with aqueous solutions of ethanol with two concentrations, degreasing the 90-95 wt% water raffinate of ethanol with petroleum ether, condensing into concrete, alcohol-depositing the concrete, merging the mother liquid with 20-80 wt% water raffinate of ethanol, concentrating and extracting with ethanol-containing acetic ester liquid, alcohol-depositing the extract and mixing with the precipitation, dissolving then passing through macro-porous absorption resin or polyamide columns, eluting with 20-80 wt% aqueous solution of ethanol, finally recrystallizing the eluent. The extraction rate of astilbin is over 50%, and the content of astilbin is over 90%.

Description

A kind of preparation method of astilbin
One, technical field
The present invention relates to a kind of method that from Chinese medicinal materials Folium Engelhardia roxburghina (Engelhardria roxburghiana Wall), prepares astilbin.
Two, background technology
Astilbin (astilbin) 3,3,4 ', 5,7-pentahydroxyflavanone3-(6-deoxy-(L-mannopyranoside)) is a kind of flavonoid compound, and nineteen fifty is extracted from the plant Herba astilbes chinensis first by KozoHayashi and Kazuhiko Ouchi and obtains.The structural formula of astilbin is as follows:
Figure A20051004094400031
Bibliographical information, astilbin have desinsection (Pest Manag.Sci.2002; 58:503-507), suppress CoA-reductase (Zhonghua Yi Xue Za Zhi (Taipei) 2001; 64:382-387), suppress aldose reductase (Biosci.Biotechnol.Biochem.1997; 61:651-654), liver protection (Prostaglandins Leukot Essent Fatty Acids 1997; (Arzneimittelforschung 2000 for 56:331-334), analgesia, Ivy extract; 50:281-285), anti-oxidant (Biosci.Biotechnol.Biochem.1996; 60:513-515) isoreactivity, astilbin can also significantly improve immunological liver injury (Eur.J.Pharmacol.1999; 377:93-100; J.Pharm.Pharmacol.2004 56:495-502), induces PHA activatory Jurkat apoptosis (Pharmacol.Res.2001; 44:135-139), suppress delayed type hypersensitivity and treatment mouse collagen type sacroiliitis (Inflamm Res.2003 by the function that suppresses activated T lymphocytes; 52 (8): 334-40.J.Pharm.Pharmacol.2003; 55:691-696) etc.
At present the main source of astilbin is therefrom to extract in sphragidite Poria cocos or the Herba astilbes chinensis, and the content of astilbin in the Rhizome of Glabrous Greenbrier is because kind, the place of production, product are received the difference in season, and content does not wait at 0.1%-2.0%.And at the Huang Qishu of ground such as Guangxi China, Guizhou growths, contained astilbin amount in its leaf all is several times as much as the content in the Rhizome of Glabrous Greenbrier, and yellow Qi leaf only is used as tealeaves for a long time and uses in the locality, obviously wasted valuable resource.
Three, summary of the invention
1, goal of the invention: the purpose of this invention is to provide a kind of preparation method that can obtain the simple astilbin that can be used for suitability for industrialized production of astilbin in a large number.
2, technical scheme: the preparation method of astilbin of the present invention is characterized in that this method may further comprise the steps:
(1) will be that ethanol and the concentration of 90%-95% (weight) is the ethanol percolate extraction of 20%-80% (weight) through over-richness successively after the Folium Engelhardia roxburghina pulverizing medicinal materials;
(2) the extraction using alcohol gained extracting solution with 90%-95% in the step (1) is condensed into medicinal extract, the medicinal extract alcohol precipitation behind petroleum ether degreasing;
(3) with in mother liquid obtained and the step (1) in the step (2) with the extraction using alcohol gained extracting solution of 20%-80% merge concentrate after, with ethyl acetate or contain the alcoholic acid ethyl acetate extraction, extract carries out alcohol precipitation;
(4) with after step (2) and step (3) the gained throw out merging dissolving, cross macroporous adsorbent resin or polyamide column, with concentration is the aqueous ethanolic solution wash-out of 20%-80% (weight), and elutriant volatilizes solvent and gets the astilbin crude product, gets the pure product of astilbin through recrystallization again;
(5) the gained recrystallization mother liquor is crossed macroporous adsorbent resin or polyamide column once more, with the aqueous ethanolic solution wash-out of 20%-80% (weight), elutriant gets the pure product of astilbin through recrystallization after volatilizing solvent again.
In step (1), before extracting pulverizing medicinal materials is become meal; The aqueous ethanolic solution of used 90%-95%, its consumption are 13 times to 20 times of used medicinal material weight, preferred 15 times; The aqueous ethanolic solution of used 20%-80%, its consumption are 5 times to 15 times of used medicinal material weight, preferred 7 times; The soak time of medicinal material is 2-12 hour, and diacolation extraction time is 1-12 hour, preferred 3-10 hour, and more preferably 5-8 hour.
In step (2), the sherwood oil consumption is a 1-4 times of weight of used medicinal material weight, preferred 2-3 times of weight, most preferably 2 times of weight; Used ethanol is the aqueous ethanolic solution of various concentration in the medicinal extract alcohol precipitation, adds the aqueous ethanolic solution post precipitation, and the ethanol ultimate density in the mixed solution can be a 0-95% weight, preferred 20%-80% weight, most preferably 50% weight.
In step (3), the volume of concentrated solution is 0.2-1 a times of used medicinal material volume, preferred 0.5 times; Extraction can be to contain 0%-20% (volume) alcoholic acid acetic acid ethyl fluid with acetic acid ethyl fluid, most preferably contains
10% (volume) alcoholic acid ethyl acetate solution; Ethyl acetate or the consumption that contains the alcoholic acid ethyl acetate be used medicinal material weight 1-4 doubly, preferred 2-3 doubly, most preferably 2.5 times.
In step (4), used polymeric adsorbent is the macroporous adsorbent resin of polymeric amide or various models, preferred macroporous adsorbent resin, more preferably nonpolar macroporous adsorption resin; Elutriant is the aqueous ethanolic solution of concentration 20%-80% (weight), the aqueous ethanolic solution of preferred 20%-70%, most preferably 30% weight; The recrystallization solvent for use can adopt water or organic solvent, and organic solvent can adopt various organic solvents commonly used such as ethanol, methyl alcohol, chloroform or ethyl acetate, the preferred alcohol aqueous solution, most preferably 50% weight aqueous ethanolic solution; The number of times of recrystallization can be 1-5 time, preferably twice.
3, beneficial effect: adopt astilbin extracting method of the present invention, (1) extracts astilbin from Folium Engelhardia roxburghina, extracts yield more than 50%, and the purity of astilbin is more than 90%.(2) astilbin of employing the inventive method gained, through measuring by 2005 editions high performance liquid chromatography of the Pharmacopoeia of the People's Republic of China, the result shows that the content of astilbin is higher than 90% in the extract, shows feasible process of the present invention.(3) astilbin extracting method of the present invention, it is simple to have extraction process, and cost is low, and the extraction yield height extracts the characteristics such as astilbin monomer purity height that obtain, and is applicable to suitability for industrialized production.
Four, embodiment
Be embodiments of the invention below, but the present invention is not limited only to described embodiment.
Embodiment 1: the Folium Engelhardia roxburghina pulverizing medicinal materials is become meal, with 95% ethanol of 10 times of medicinal material weight and the 80% ethanol diacolation extraction respectively of 15 times of amounts, collect percolate.95% ethanol extract with petroleum ether degreasing after, be concentrated into medicinal extract, adding ethanol, to make strength of solution be 20% aqueous ethanolic solution, and the dissolving back is placed and analysed precipitation, divides and gets precipitation, mother liquor and 80% ethanol extract merge, be concentrated into every milliliter 3 gram crude drug, with the ethyl acetate extraction that is equivalent to 2 times of amounts of crude drug, acetic acid ethyl ester extract is concentrated into medicinal extract, adding aqueous ethanolic solution, to make strength of solution be 20% aqueous ethanolic solution, and the dissolving back is placed and analysed precipitation.Divide and get precipitation, ethanol precipitation twice gained precipitation is merged, cross polyamide column after the water dissolution, with distilled water wash post bed, with 60% weight aqueous ethanolic solution wash-out, after elutriant is flung to solvent, 20% weight aqueous ethanolic solution recrystallization gets astilbin, mother liquor is flung to the alcohol back after polyamide column behind the recrystallization, and 60% weight aqueous ethanolic solution wash-out, elutriant are used 20% weight ethanol water recrystallization after flinging to solvent again.Get astilbin, extraction yield is 51.4%, and astilbin content is 90%.
Embodiment 2: the Folium Engelhardia roxburghina pulverizing medicinal materials is become meal, 60% ethanol diacolation extraction respectively with 15 times of 90% ethanol of medicinal material weight and 10 times of amounts, collect 90% ethanol extract and 60% ethanol extract, 90% ethanol extract is concentrated into medicinal extract with extracting solution after with petroleum ether degreasing, it is the aqueous ethanolic solution of 60% weight that adding ethanol makes strength of solution, dissolving, precipitation is analysed in placement, mother liquor merges behind 60% ethanol extract and the aforementioned alcohol precipitation, concentrate the back with containing 5% alcoholic acid ethyl acetate extraction, acetic acid ethyl ester extract is concentrated into and adds ethanol behind the medicinal extract to make alcohol concn be 60%, the dissolving back is placed and is analysed precipitation, and ethanol precipitation twice gained precipitation is merged, and crosses LSA-10 macroporous resin (blue dark production the in Xi'an) post after the water dissolution, with 70% ethanolic soln wash-out, after elutriant was flung to solvent, 60% ethyl alcohol recrystallization got the astilbin monomer, and mother liquor is flung to the alcohol back after the LSA-7 macroporous resin column behind the recrystallization, 70% ethanol elution, elutriant are used 60% ethyl alcohol recrystallization after flinging to solvent again.Get astilbin, content is 90%, and extraction yield is 53.5%.
Embodiment 3: the Folium Engelhardia roxburghina pulverizing medicinal materials, extract with 20 times of 95% ethanol of medicinal material weight and 8 times of amount 20% ethanol gradient diacolations, collect 95% ethanol extract and 40% ethanol extract respectively, 95% ethanol extract is concentrated into medicinal extract with extracting solution after with petroleum ether degreasing, place after the water dissolution and analyse precipitation, mother liquor merges concentrated back with containing 20% alcoholic acid ethyl acetate extraction behind 40% ethanol extract and the aforementioned alcohol precipitation, ethyl acetate extract is concentrated into and adds ethanol behind the medicinal extract to make alcohol concn be 80%, place the dissolving back, ethanol precipitation twice gained precipitation is merged, cross polyamide column after the water dissolution, with 50% ethanolic soln wash-out, after elutriant is flung to solvent, 70% ethyl alcohol recrystallization gets the astilbin monomer, mother liquor is flung to the alcohol back after polyamide column behind the recrystallization, and 50% ethanol elution, elutriant are used 70% ethyl alcohol recrystallization after flinging to solvent again.Content is 90% astilbin, extraction yield is 52.8%.
Embodiment 4: the experiment of astilbin purity testing.It is an amount of to get the astilbin monomer that the said extracted method prepares, and the dissolve with methanol constant volume behind the filtering with microporous membrane, injects high performance liquid chromatograph in volumetric flask, with Pharmacopoeia of the People's Republic of China high effective liquid chromatography for measuring content in 2005.
Chromatographic condition: Water 600 high performance liquid chromatographs, Waters 2487 UV-detector; Chromatographic column: Symmetry C18 post (4.6mm * 250mm, 5 μ m); Moving phase: methyl alcohol-Glacial acetic acid-water (45: 1: 54); Detect wavelength: 291nm; Column temperature: 30 ℃; Flow velocity: 1ml/min; Sample size: 5 μ l.
The reference substance astilbin, self-control, colourless needle crystal, mp182~186 ℃, through mensuration such as UV, IR, 1H-NMR, 13C-NMR, MS, its data are consistent with bibliographical information, are accredited as astilbin.Be single spot on the TLC collection of illustrative plates, HPLC detects to unimodal, and normalization method content is more than 99%.
Measure as stated above, the content of astilbin is more than 90% in the extract.
In sum, astilbin extracting method of the present invention can extract from the medicinal material that contains astilbin effectively and obtain astilbin, and astilbin content all is higher than more than 90% in the extract, and the technology simple possible, and cost is low, is applicable to suitability for industrialized production.
The extracting method of astilbin disclosed in this invention has as above been described.But need to understand and wherein comprised variation understood by one of ordinary skill in the art and change.These variations and change are also contained in the basis that claim limits
In the scope of invention.

Claims (10)

1, a kind of preparation method of astilbin is characterized in that this method may further comprise the steps:
(1) will be that ethanol and the concentration of 90%-95% (weight) is the ethanol percolate extraction of 20%-80% (weight) through over-richness successively after the Folium Engelhardia roxburghina pulverizing medicinal materials;
(2) the extraction using alcohol gained extracting solution with 90%-95% in the step (1) is condensed into medicinal extract, the medicinal extract alcohol precipitation behind petroleum ether degreasing;
(3) with in mother liquid obtained and the step (1) in the step (2) with the extraction using alcohol gained extracting solution of 20%-80% merge concentrate after, with ethyl acetate or contain the alcoholic acid ethyl acetate extraction, extract carries out alcohol precipitation;
(4) with after step (2) and step (3) the gained throw out merging dissolving, cross macroporous adsorbent resin or polyamide column, with concentration is the aqueous ethanolic solution wash-out of 20%-80% (weight), and elutriant volatilizes solvent and gets the astilbin crude product, gets the pure product of astilbin through recrystallization again;
(5) the gained recrystallization mother liquor is crossed macroporous adsorbent resin or polyamide column once more, with the aqueous ethanolic solution wash-out of 20%-80% (weight), elutriant gets the pure product of astilbin through recrystallization after volatilizing solvent again.
2, the preparation method of a kind of astilbin according to claim 1 is characterized in that in step (1), and the aqueous ethanolic solution of used 90%-95%, its consumption are 13-20 times of used medicinal material weight.
3, the preparation method of a kind of astilbin according to claim 1 is characterized in that in step (1), and the aqueous ethanolic solution of used 20%-80%, its consumption are 5-15 times of used medicinal material weight.
4, the preparation method of a kind of astilbin according to claim 1 is characterized in that in step (1), the soak time of medicinal material is 2-12 hour, and diacolation extraction time is 1-12 hour.
5, the preparation method of a kind of astilbin according to claim 1 is characterized in that in step (2), and the sherwood oil consumption is 1-4 a times of used medicinal material weight.
6, the preparation method of a kind of astilbin according to claim 1 is characterized in that in step (3), and the volume of concentrated solution is 0.2-1 a times of used medicinal material volume.
7, the preparation method of a kind of astilbin according to claim 1 is characterized in that in step (3), ethyl acetate or the consumption that contains the alcoholic acid ethyl acetate be used medicinal material weight 1-4 doubly.
8, the preparation method of a kind of astilbin according to claim 1 is characterized in that in step (4), used polymeric adsorbent is the macroporous adsorbent resin of polymeric amide or various models.
9, the preparation method of a kind of astilbin according to claim 1 is characterized in that in step (4), elutriant is the aqueous ethanolic solution of concentration 20%-80% (weight).
10, the preparation method of a kind of astilbin according to claim 1 is characterized in that the recrystallization solvent for use can adopt water or organic solvent in step (4), and organic solvent can adopt ethanol, methyl alcohol, chloroform or ethyl acetate organic solvent; The number of times of recrystallization can be 1-5 time.
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Cited By (14)

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CN100348610C (en) * 2005-09-01 2007-11-14 桂林莱茵生物科技股份有限公司 Method for extracting astilbin from engelhardtia leaves
CN101935332A (en) * 2010-07-16 2011-01-05 沈阳药科大学 Preparation method and application of 5,7,4'-trihydroxyl8-methoxyl-3-O-alpha-L-rhamnoside and active composition thereof
CN101972287A (en) * 2010-10-18 2011-02-16 山东大学威海分校 Preparation method of Chinese astilbe extract and purpose thereof
CN102020690A (en) * 2010-11-09 2011-04-20 苏州派腾生物医药科技有限公司 Preparation method of astilbin
CN102432652A (en) * 2010-09-29 2012-05-02 苏州瑞蓝博中药技术开发有限公司 Method for extracting astilbin from china root
CN103012522A (en) * 2012-12-28 2013-04-03 顾玲 Purification process of astilbin
CN103768082A (en) * 2012-10-18 2014-05-07 滨州医学院 Application of astilbin to preparation of medicament for treating or preventing diabetes accompanied with stroke
CN105061531A (en) * 2015-07-29 2015-11-18 成都大学 Astilbe chinensis glycoside derivatives and preparation method thereof
CN106565804A (en) * 2016-10-10 2017-04-19 广西来宾绿翔生物科技有限公司 Extraction technology of Engelhardia roxburghiana Wall leaf astilbin
CN107056858A (en) * 2017-04-28 2017-08-18 南宁馨艺荣生物科技有限公司 Process for extracting astilbin from engelhardtia leaves
CN107951923A (en) * 2017-12-07 2018-04-24 广西壮族自治区中医药研究院 A kind of preparation method of astragalus leaf flavonoids and its application in protection blood vessel drug eluting is prepared
CN109369749A (en) * 2018-11-30 2019-02-22 陕西嘉禾生物科技股份有限公司 A kind of preparation method of Astilbin
CN111437302A (en) * 2015-05-25 2020-07-24 蔡世珍 Application of extract of engelhardtia leaves after water extraction and macroporous resin treatment in preparation of diabetes drugs and analysis method thereof
CN111440221A (en) * 2019-12-13 2020-07-24 湖南甜蔓生物科技有限公司 Astilbin prepared from Engelhardtia chrysolepis Hance leaf and its preparation method

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Publication number Priority date Publication date Assignee Title
CN100348610C (en) * 2005-09-01 2007-11-14 桂林莱茵生物科技股份有限公司 Method for extracting astilbin from engelhardtia leaves
CN101935332A (en) * 2010-07-16 2011-01-05 沈阳药科大学 Preparation method and application of 5,7,4'-trihydroxyl8-methoxyl-3-O-alpha-L-rhamnoside and active composition thereof
CN101935332B (en) * 2010-07-16 2014-06-25 沈阳药科大学 Preparation method and application of 5,7,4'-trihydroxyl8-methoxyl-3-O-alpha-L-rhamnoside and active composition thereof
CN102432652A (en) * 2010-09-29 2012-05-02 苏州瑞蓝博中药技术开发有限公司 Method for extracting astilbin from china root
CN101972287A (en) * 2010-10-18 2011-02-16 山东大学威海分校 Preparation method of Chinese astilbe extract and purpose thereof
CN102020690A (en) * 2010-11-09 2011-04-20 苏州派腾生物医药科技有限公司 Preparation method of astilbin
CN103768082B (en) * 2012-10-18 2016-06-15 滨州医学院 Astilbin merges the application in apoplexy medicine in preparation treatment or prevention diabetes
CN103768082A (en) * 2012-10-18 2014-05-07 滨州医学院 Application of astilbin to preparation of medicament for treating or preventing diabetes accompanied with stroke
CN103012522A (en) * 2012-12-28 2013-04-03 顾玲 Purification process of astilbin
CN103012522B (en) * 2012-12-28 2015-03-25 顾玲 Purification process of astilbin
CN111437302A (en) * 2015-05-25 2020-07-24 蔡世珍 Application of extract of engelhardtia leaves after water extraction and macroporous resin treatment in preparation of diabetes drugs and analysis method thereof
CN111437302B (en) * 2015-05-25 2022-03-01 苏州优诺康医药科技有限公司 Application of extract of engelhardtia leaves after water extraction and macroporous resin treatment in preparation of diabetes drugs and analysis method thereof
CN105061531A (en) * 2015-07-29 2015-11-18 成都大学 Astilbe chinensis glycoside derivatives and preparation method thereof
CN106565804A (en) * 2016-10-10 2017-04-19 广西来宾绿翔生物科技有限公司 Extraction technology of Engelhardia roxburghiana Wall leaf astilbin
CN107056858A (en) * 2017-04-28 2017-08-18 南宁馨艺荣生物科技有限公司 Process for extracting astilbin from engelhardtia leaves
CN107951923A (en) * 2017-12-07 2018-04-24 广西壮族自治区中医药研究院 A kind of preparation method of astragalus leaf flavonoids and its application in protection blood vessel drug eluting is prepared
CN109369749A (en) * 2018-11-30 2019-02-22 陕西嘉禾生物科技股份有限公司 A kind of preparation method of Astilbin
CN109369749B (en) * 2018-11-30 2021-10-01 陕西嘉禾生物科技股份有限公司 Preparation method of astilbin
CN111440221A (en) * 2019-12-13 2020-07-24 湖南甜蔓生物科技有限公司 Astilbin prepared from Engelhardtia chrysolepis Hance leaf and its preparation method
CN111440221B (en) * 2019-12-13 2021-11-26 湖南甜蔓生物科技有限公司 Astilbin prepared from Engelhardtia chrysolepis Hance leaf and its preparation method

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