CN102492005B - Method for preparing paeoniflorin and albiflorin - Google Patents
Method for preparing paeoniflorin and albiflorin Download PDFInfo
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- CN102492005B CN102492005B CN201110410067.9A CN201110410067A CN102492005B CN 102492005 B CN102492005 B CN 102492005B CN 201110410067 A CN201110410067 A CN 201110410067A CN 102492005 B CN102492005 B CN 102492005B
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Abstract
The invention discloses a method for preparing paeoniflorin and albiflorin, which mainly includes the following steps: selecting peony plant raw materials containing the paeoniflorin and the albiflorin, adopting water or alcohol-water mixed solvent to perform extraction, mixing extract, concentrating, filtering, absorbing the obtained crude extract by adopting pre-preprocessed macroporous resin, performing gradient elution by using ethanol-water mixed solvent, collecting 30% to 75% of ethanol elution parts eluent to perform concentration and drying. The obtained refined extract adopts pressurized column chromatography, using silica gel and modified silica gel as fillers, appropriate organic solvent is separated in mobile phase, flow parts containing the paeoniflorin and the albiflorin are collected respectively, concentrated and dried to obtain paeoniflorin finished products and albiflorin finished products with the purity more than 90%. The method for preparing the paeoniflorin and the albiflorin is concise in process, strong in operability, convenient in automation, capable of achieving comprehensive utilization of plant resources, convenient in solvent recycling, low in energy consumption, high in product purity, easy to achieve and high in industrialization.
Description
Technical field
The present invention relates to the preparation method of a kind of peoniflorin and albiflorin.
Technical background
Peoniflorin (paeoniflorin) and albiflorin are (also known as lactone glucoside of Radix Paeoniae, albiflorin) be a kind of monoterpene glycosides composition, ubiquity in Paeoniaceae plant, mainly contain effective constituent and quality control standard in the traditional Chinese medicine root of herbaceous peony, the radix paeoniae rubrathe, Tree Peony Bark, there is multiple pharmacological effect and purposes, the total glycosides of white peony root is a kind of medicine for the treatment of rheumatoid arthritis in China, and peoniflorin and albiflorin can be used as effective ingredient and be applied to relevant medicine and functional food field.
Preparation technology's research papers of Radix Paeoniae Alba total glycosides mainly concentrates on China.You Song etc. (Chinese Patent Application No. 02133298.3) disclose one " composition and method of making the same of peoniflorin and lactone glucoside of Radix Paeoniae ", described composition extraction and isolation from Chinese herbaceous peony obtains, wherein peoniflorin and lactone glucoside of Radix Paeoniae ratio is in the composition 7: 3 ~ 9: 1, and its preparation technology is refining mainly through polymeric adsorbent, alumina column chromatography and silica gel column chromatography obtain.Zhang Xiantao etc. (Chinese Patent Application No. 200510041212.5) disclose one " preparation method of extract product of paeoniflorin ", described technique mainly adopts extraction using alcohol radix paeoniae rubrathe medicinal material, after upper macroporous resin, ethanol elution, after elutriant is concentrated, upper polyamide resin, obtains content more than 90% peoniflorin.Zhu Jingjian etc. (Chinese Patent Application No. 02110973.7) disclose the one method of glycoside compound monomer, Extraction and separation " in the Chinese herbaceous peony ", described composition comprises peoniflorin, lactone glucoside of Radix Paeoniae, benzoylpaeoniflorin and Hydroxy peoniflorin, its method mainly adopts the root of herbaceous peony or the radix paeoniae rubrathe swelling in alcohol solution, reflux, is concentrated into medicinal extract, uses acetone soln supersound extraction, concentrated, silica gel mixed sample, the rough segmentation of upper vacuum chromatographic column, more repeatedly carry out distribution chromatography acquisition through silicagel column.Shi Renbing etc. (Chinese Patent Application No. 200710111231. ×) disclose one " extract of total glucosides of paeony and preparation method thereof ", described extract mainly comprises peoniflorin, RADIX PAEONIAE ALBA glycosides, lacdtlorin Ⅲ, paeonilactone A, B, C, oxypaeoniflorin, benzoylpaeoniflorin and derivative thereof etc., can prepare from each plant parts of Paeoniaceae.
By studying for a long period of time, adopt the technique of macroporous resin technology purifying Radix Paeoniae Alba total glycosides comparatively ripe at present, but peoniflorin and albiflorin can not separate, the technology such as general solvent extraction are also difficult to reach separating effect.Bibliographical information adopts method separation and purification peoniflorin and the albiflorin monomers such as normal pressure silica gel column chromatography, high-speed countercurrent chromatography, but the former post effect is lower, dress post and detect complicated operation, and the latter needs special plant and instrument, and the two is all difficult to realize suitability for industrialized production.Peoniflorin and the albiflorin monomer of current mass-producing there is no commercially available prod, explore feasible industrialized manufacturing technique, are have technical barrier to be solved at present.
Summary of the invention
The object of this invention is to provide a kind of purity to be greater than 90%, to be easy to realize the peoniflorin of industrialization and albiflorin preparation technology.
The method preparing peoniflorin and albiflorin provided by the invention comprises the following steps:
(1) choose the Paeoniaceae plant material containing peoniflorin and albiflorin, adopt water or alcohol-water mixed solvent to extract, extracting solution merges, concentrated, filters, obtains crude extract;
(2) by (1) gained crude extract, adopt the good macroporous resin of pre-treatment to adsorb, then press 0-20%, 30-75% ethanol gradient elution with alcohol-water mixed solvent, collect 30-75% alcohol elution elutriant, concentrated, dry, obtain refining extract;
(3) extract is refined by (2) gained, adopt pressured column chromatogram, with silica gel or modified silica-gel for filler, suitable organic solvents is that moving phase is separated, collect the stream part containing peoniflorin and albiflorin respectively, concentrated, dry, peoniflorin and albiflorin finished product that purity is greater than 90% can be obtained.
Paeoniaceae plant described in described processing step (1) is any one in the root of herbaceous peony, the radix paeoniae rubrathe, tree peony, and described plant material is any one in roots of plants, stem, leaf, rhizome.Extraction solvent is any one in water, alcohol-water.Described extracting method can be in refluxing extraction, supersound extraction, microwave radiation exaraction, countercurrent extraction any one.
In described processing step (2), described macroporous resin is polystyrene or acrylic resin, wherein preferred nonpolar or low-pole macroporous resin.0-10%, 30-70% ethanol gradient elution is preferably pressed during macroporous resin gradient elution.
Pressured column chromatogram described in described processing step (3) is low pressure or middle compression leg chromatogram, and column length is 10-100 cm range, preferred 15-100 centimetre; Column internal diameter can be chosen as 2-100 cm range according to need of production, preferred 10-50 centimetre.Described filler can be silica gel, and described moving phase is any one in chloroform-methanol, methylene chloride-methanol, acetate-methanol, ethyl acetate-ethanol.Described filler also can be carbon 18 modified silica-gel, and described moving phase is any one in methanol-water, methanol-water-organic acid, the wherein preferred volatile first of organic acid or acetic acid.Described stream part containing peoniflorin and albiflorin can adopt online ultraviolet detection, or the thin layer of off-line detects or Liquid Detection.
The present invention is by peoniflorin and albiflorin technical study, the technology of preparing route completed has following characteristic and advantage: (1) medicinal material can select the various plant material of Paeoniaceae containing peoniflorin and albiflorin, comprise in the root of herbaceous peony, the radix paeoniae rubrathe, tree peony any one, comprise any one position in the root of plant, stem, leaf, rhizome, expand and enriched effective comprehensive utilization of plant resources; (2) adopt preferred macroporous resin gradient elution technique, be effectively enriched the component being rich in peoniflorin and albiflorin, simplify subsequent purification technique burden; (3) novelty application low pressure or middle compression leg chromatogram operation, achieve automatization and the operability of monomer purifying operation, successfully obtains the monomer finished product that purity is greater than 90%.The economical rationality of present invention process route, efficiency is high, energy consumption is low, can realize making full use of of plant resources, and solvent is convenient to reclaim and recycle, easily realizes suitability for industrialized production.
Content of the present invention is completed by lot of experiments, process optimization analysis, is described with following specific embodiment.
Embodiment
Peoniflorin of the present invention and albiflorin are by the method manufacture represented by following examples, and involved method is the technique means that those skilled in the art can grasp and use.But following examples must not be interpreted as the restriction to this area invention claim of going up in all senses.
Embodiment 1 macroporous resin Static Adsorptive capacity is investigated
Take 1kg root of herbaceous peony medicine materical crude slice, with 8L70% alcohol reflux 2 times, each 2h, filter, merging filtrate, is evaporated to without alcohol taste, adjusts liquid and makes every 1ml liquid be equivalent to 0.5g crude drug, for subsequent use.
Take the heavy 1.00g of each model resin dry, be placed in the tool plug Erlenmeyer flask of 10 50ml respectively, add white paeony root extract (0.5g crude drug/ml) 10ml, vibrate under 35 DEG C of conditions 6h in constant temperature oscillation case, vibration velocity is 180prm, by the white paeony root extract vacuum filtration after absorption, filtrate, through suitably dilution, measures albiflorin and albiflorin content with reference to 2010 editions official methods HPLC method.The resin adsorbed washes 3 times, after vacuum-drying with water, adds 10ml95% ethanol, and vibrate under 35 DEG C of conditions 6h equally in constant temperature oscillation case, and vibration velocity is 180prm, carries out desorption.Stripping liquid measures peoniflorin and albiflorin content with HPLC after suitably diluting.The resin adsorbed washes 3 times, after vacuum-drying with water, adds 10ml95% ethanol, and vibrate under 35 DEG C of conditions 6h equally in constant temperature oscillation case, and vibration velocity is 180prm, carries out desorption.Stripping liquid measures peoniflorin and albiflorin content with HPLC after suitably diluting.
Evaluating resin is carried out by calculating adsorptive capacity and desorption efficiency.Adsorptive capacity calculation formula (1) and desorption efficiency calculation formula (2) are;
(1)q
e＝(C
0-C
e)V
i/W；(2)D＝C
dV
d/(C
0-C
e)V
i×100％
In formula (1), q
efor resin absorption amount (mg/g), C
0initial concentration solution, C
eadsorb saturated rear strength of solution, V
ifor sample volume, W is resin dry weight.In formula (2), D is desorption efficiency, C
dfor the concentration of the composition to be measured of elutriant after desorption, V
dfor effluent volume, C
0, C
e, V
iwith upper same.The results are shown in Table 1.
The each model resin of table 1 is to the maximal absorptive capacity of Chinese herbaceous peony and desorption efficiency
Conclusion: ten kinds of resins can adsorption and de-adsorption to peoniflorin and albiflorin, but LX17 is better with polystyrene low-pole Resin A B-8 and LX38, acrylic acid series Semi-polarity resin.
The preparation of embodiment 2 Radix Paeoniae Alba extract
Take 40kg white Peony Root, spend the night by 70% alcohol immersion, refluxing extraction 2 times, each 2h, filter, merging filtrate, rotary evaporation, to without alcohol taste, adjusts liquid and makes every 1ml liquid be equivalent to 0.5g crude drug, for subsequent use.Take 120kg (weight in wet base) LX38 resin, load in stainless steel column (300 × 2300cm), column volume is 60L, loading, after absorption 1h, first use water 300L, 10% ethanol 300L removes impurity, use 50% ethanol 360L wash-out peoniflorin and albiflorin again, finally use 95% ethanol regenerating resin, flow velocity is 150-200L/h, 50% ethanol position is concentrated evaporate to dryness and obtains 2.52kg, wherein peoniflorin purity is 24%, and albiflorin is 16%.
The preparation of embodiment 3 Radix Paeoniae Alba extract
Take 40kg root of herbaceous peony medicine materical crude slice, spend the night by 70% alcohol immersion, refluxing extraction 2 times, each 2h, filter, merging filtrate, rotary evaporation, to without alcohol taste, adjusts liquid and makes every 1ml liquid be equivalent to 0.5g crude drug, for subsequent use.Take 120kg (weight in wet base) AB-8 resin, load in stainless steel column (300 × 2300cm), column volume is 60L, loading, after absorption 1h, first use water 300L, 10% ethanol 300L removes impurity, use 50% ethanol 360L wash-out peoniflorin and albiflorin again, finally use 95% ethanol regenerating resin, flow velocity is 150-200L/h, 50% ethanol position is concentrated evaporate to dryness and obtains 2.32kg, wherein peoniflorin purity is 22%, and albiflorin is 12%.
The preparation of embodiment 4 Radix Paeoniae Alba extract
Take 40kg root of herbaceous peony rhizome, spend the night by 70% alcohol immersion, refluxing extraction 2 times, each 2h, filter, merging filtrate, rotary evaporation, to without alcohol taste, adjusts liquid and makes every 1ml liquid be equivalent to 0.5g crude drug, for subsequent use.Take 120kg (weight in wet base) LX17 resin, load in stainless steel column (300 × 2300cm), column volume is 60L, loading, after absorption 1h, first uses water 300L, 10% ethanol 300L removes impurity, use 50% ethanol 360L wash-out peoniflorin and albiflorin again, finally use 95% ethanol regenerating resin, flow velocity is 150-200L/h, 50% ethanol position is concentrated evaporate to dryness, obtain 2.84kg, wherein peoniflorin purity is 27%, and albiflorin is 18%.
Embodiment 5 silica gel medium pressure Column preparation monomer constituents
Example 2 gained Radix Paeoniae Alba extract 8g, with dissolve with methanol, adds 8g 200-300 order silica gel mixed sample, compression leg systematic position in employing, fills post (150 × 35mm i.d.) with silica gel H, uses eluent ethyl acetate 1000ml, flow velocity 50mL/min, use ethyl acetate again: methyl alcohol=95: 5 wash-outs, ultraviolet 230nm detects, and collects peoniflorin stream part and albiflorin stream part successively, concentrating under reduced pressure, drying, obtain peoniflorin 2.8g, albiflorin 1.2g, purity is respectively 95.4% and 92.2%.
Embodiment 6 silica gel medium pressure Column preparation monomer constituents
Adopt chloroform: methyl alcohol (15: 1 to 13: 1,90min) gradient elution, all the other Parameter Conditions, with embodiment 5, obtain peoniflorin 2.5g, albiflorin 1.0g, and purity is respectively 96.1% and 91.2%.
Reverse phase silica gel Column preparation monomer constituents is pressed in embodiment 7
Example 2 gained Radix Paeoniae Alba extract 10g, compression leg systematic position in employing, fills post (400 × 70mmi.d.) with reverse phase silica gel C, sample 100mL water dissolution loading, with 18% methyl alcohol isocratic elution, flow velocity 50mL/min, ultraviolet 230nm detect, and collect peoniflorin stream part and albiflorin stream part successively, concentrating under reduced pressure, drying, obtain peoniflorin 3.3g, albiflorin 1.4g, purity is respectively 93.6% and 90.5%.
Reverse phase silica gel Column preparation monomer constituents is pressed in embodiment 8
Adopt 18% methyl alcohol (containing 1%HAc) isocratic elution, all the other Parameter Conditions, with embodiment 7, obtain peoniflorin 3.7g, albiflorin 1.6g, and purity is respectively 98.1% and 94.2%.
Claims (1)
1. a preparation method for peoniflorin and albiflorin, is characterized in that the preparation method of described peoniflorin and albiflorin is as follows:
(1) choose the Paeoniaceae plant material containing peoniflorin and albiflorin, adopt water or alcohol-water mixed solvent to extract, extracting solution merges, concentrated, filters, obtains crude extract;
(2) by (1) gained crude extract, adopt the good macroporous resin of pre-treatment to adsorb, then press 0-20%, 30-75% ethanol gradient elution with alcohol-water mixed solvent, collect 30
-75% alcohol elution elutriant, concentrated, dry, obtain refining extract;
(3) extract is refined by (2) gained, adopt pressured column chromatogram, with silica gel or modified silica-gel for filler, suitable organic solvents is that moving phase is separated, collect the stream part containing peoniflorin and albiflorin respectively, concentrated, dry, peoniflorin and albiflorin finished product that purity is greater than 90% can be obtained;
Wherein:
Described in preparation method's step (1), alcohol is ethanol, and extracting method is any one in refluxing extraction, supersound extraction, microwave radiation exaraction, countercurrent extraction;
Macroporous resin described in preparation method's step (2) is polystyrene low-pole resin LX38 or acrylic acid series polar resin LX17; Pressured column chromatogram described in preparation method's step (3) is low pressure or middle compression leg chromatogram, and column length is 10-100 cm range, and column internal diameter is 2-100 cm range;
Described in preparation method's step (3), filler is silica gel, and described moving phase is any one in chloroform-methanol, acetate-methanol;
Or modified silica-gel described in preparation method's step (3) is carbon 18 modified silica-gel, described moving phase is any one in methanol-water, methanol-water-organic acid;
Described Paeoniaceae plant is any one in the root of herbaceous peony, the radix paeoniae rubrathe, tree peony, and described plant material is any one in roots of plants, stem, leaf, rhizome;
Stream part containing peoniflorin and albiflorin described in its preparation methods steps (3) adopts online ultraviolet detection.
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Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103044503A (en) * | 2012-12-24 | 2013-04-17 | 浙江工业大学 | Method for rapidly and efficiently extracting paeoniflorin and albiflorin |
| CN104072550B (en) * | 2013-03-25 | 2018-05-29 | 河北以岭医药研究院有限公司 | The separation method of monoterpene and saponin component in Chinese medicine composition autonomic drug intermediate |
| CN103584093B (en) * | 2013-10-29 | 2016-05-18 | 无限极（中国）有限公司 | Radix paeoniae alba extraction has the application in health food or the cosmetics of radioresistance and senile-resistant efficacy in preparation |
| CN103784523A (en) * | 2014-01-28 | 2014-05-14 | 齐鲁工业大学 | Peony polyphenol extraction process |
| CN111122731B (en) * | 2019-12-27 | 2022-09-06 | 贵州景峰注射剂有限公司 | Quality detection method for radix paeoniae rubra |
| CN112807257A (en) * | 2020-03-23 | 2021-05-18 | 上海铮信生物科技有限公司 | Preparation method of radix Paeoniae extract |
| CN111388542A (en) * | 2020-03-24 | 2020-07-10 | 首都医科大学 | Method for extracting monoterpene glycoside active ingredient from non-medicinal part of radix paeoniae alba |
| CN113750140A (en) * | 2021-04-14 | 2021-12-07 | 宁波职业技术学院 | Application of total glucosides of paeony in preparing medicine for treating rheumatoid arthritis |
| CN113769692B (en) * | 2021-09-29 | 2023-06-30 | 四川聚元药业集团有限公司 | Preparation reation kettle of high purity white paeony root glycoside |
| CN115677796A (en) * | 2022-11-23 | 2023-02-03 | 四川聚元药业集团有限公司 | Method for extracting paeoniflorin from white paeony root |
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