CN100494393C - Technique for producing high purity chlorogenic acid in industrialization scale - Google Patents
Technique for producing high purity chlorogenic acid in industrialization scale Download PDFInfo
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- CN100494393C CN100494393C CNB2005100207065A CN200510020706A CN100494393C CN 100494393 C CN100494393 C CN 100494393C CN B2005100207065 A CNB2005100207065 A CN B2005100207065A CN 200510020706 A CN200510020706 A CN 200510020706A CN 100494393 C CN100494393 C CN 100494393C
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Abstract
This invention relates to industrial production technique of Chlorogenic Acid. When we add compounded enzymes, it can enhance the extraction rate. This technology is a breakthrough of Chlorogenic Acid production, because the reductive solvent protects Chlorogenic Acid groups, avoids it to be oxidated. It works out problems such as phenol hydroxyl oxidated, alkene diethylene glycol dinitrate bond hydrolysis, isomerization of seriate molecular lactone migration. The first enterprise, who has adapted this technology, has completed the industrialization produces of the high pure chlorogenic acid, about 500kg per year. Its purity reaches 99%, absolutely satisfies the production criterion of freeze-dry powder. In the production the solvent amount are few, the product solvent remains may meet the national related requirements and each criterion.
Description
Technical field the present invention relates to the preparation technology of medicine material, particularly the technology of high purity chlorogenic acid in industrialization scale production.
" research of the pure product of chlorogenic acid extracting from Folium Eucommiae " that background technology 1. is write at Ma Xihan etc. is (referring to " Xibei Forest College's journal " 1996,11 (2): 58-60), adopt chloroform degreasing, chemical extraction, inorganic salt to sink, this processing method fails effectively to remove the impurity (as protein, colloid, Mierocrystalline cellulose) in the Folium Eucommiae, make chlorogenic acid be difficult to stripping, and only be applicable to the low dose of preparation in laboratory.2. " extraction of the chlorogenic acid material research in the Folium Eucommiae " of being write at Wang Hongwu etc. is (referring to " Jiangxi Normal University's journal " (natural science edition) 1997,21 (4): 339-341), what adopt is solvent extraction, alkaline Pb (OAc) and KOAc precipitation, the dissolution extraction recrystallization makes again, but plumbous meeting have residual in the chlorogenic acid product, leaded extraction waste liquid can cause detrimentally affect to environment, and therefore, this method is not suitable for large-scale industrialization production.3. " extraction of Folium Eucommiae chlorogenic acid, separation and the evaluation " of writing at Qi Xiangyang etc. is (referring to " plant resources and environment " 1998,7 (1): 61-62), adopt flooding, 101 resin isolation, organic solvent extraction purifying, its chlorogenic acid contents only is 24.33%.Above Technology to chlorogenic acid extract, various influence factors in the purge process do not give to take all factors into consideration and solve, all can not reach the content more than 99% and the rule of suitability for industrialized production and touch.
Summary of the invention the present invention proposes a kind of the solve contained phenolic hydroxyl group oxidation of chlorogenic acid in the production process, olefin(e) acid ester linkage hydrolyzing and intramolecularly ester group migration and problem such as isomery takes place in succession just in order to overcome above-mentioned weak point of the prior art; And breakthrough suitability for industrialized production yield is low, content does not reach the bottleneck that requires more than 99%.
Technique for producing high purity chlorogenic acid in industrialization scale branch following steps of the present invention are finished:
1. pre-treatment: the sherwood oil that adds 2 to the 3 times of weight of Folium Eucommiae after the pulverizing takes off ester with Folium Eucommiae, filters the compound bio-enzyme preparation that adds 0.5-1% in the back in Folium Eucommiae and also puts into encloses container and store 24-36 hour; Wherein the compound bio zymin is made up of 45%-65% cellulase, 5%-10% proteolytic enzyme and 30%-45% polygalacturonase.
2. extract: with the 4-5 of Folium Eucommiae weight doubly, concentration is ethanol or the butanols of 40%-60%, extracts 0.5-1 hour under 40 ℃ of-50 ℃ of temperature, extracts twice with identical condition, centrifuging is also squeezed;
3. purify: add 2%-3% composite reduction solvent in extracting solution, this composite reduction solvent is by being to have than the inorganic salt of strong reducing property to form, as being made up of 85%-95% Sulfothiorine and 5%-15% sodium bisulfite.The extracting solution that is added with the reduction solvent is concentrated the back transfer pH to 2-3 with concentrated hydrochloric acid, with twice of concentrated solution 3-4 ethyl acetate extraction doubly, get ethyl acetate layer, wherein adding the neutralization of 3%-5%NaOH liquid makes the chlorogenic acid in the ethyl acetate enter water, separate out the chlorogenic acid precipitation with concentrated hydrochloric acid acid again after the aqueous phase separation, with the incomplete dissolving-recrystallization of a spot of ethyl acetate, be drying to obtain the chlorogenic acid crude product after the precipitate and separate, content is generally about 95%-98%, extraction yield about 2.7%;
4. finished product is refining: chlorogenic acid crude product and deionized water are with the solid-liquid ratio of 1:3 or 1:4, at the high pure nitrogen that leads to 99.99% continuously, keep malleation, pressure reduction〉under the condition of 5Pa, dissolving also adds the 8%-10% activated carbon and is heated to 50-60 ℃ of backflow 0.5-1 hour, filtration, crystallisation by cooling, crystallization with 2-5 analytical pure acetone doubly clean, vacuum-drying obtains 99% above high-purity chlorogenic acid.
The description of drawings Figure of description is detailed process flow figure of the present invention.
Below be the good effect that the present invention compared with prior art has:
1. add dissolution rate and reduction solvent protection chlorogenic acid molecular radical that biological complex enzyme improves chlorogenic acid Avoiding oxidized technology is the important breakthrough that high-purity chlorogenic acid is produced, and use of the present invention makes applicant head The enterprise that family finishes industrial-scale production high-purity chlorogenic acid (content is more than 99%), annual production reaches 500 Kilogram.
2. chlorogenic acid purity reaches more than 99%, can satisfy the indices of producing freeze-dried powder fully.
3. solvent load is few, and the product dissolvent residual can reach national relevant requirements and indices
Specific embodiments:
Embodiment 1: a kind of technique for producing high purity chlorogenic acid in industrialization scale, it is the Folium Eucommiae that to pulverize, sherwood oil with 2 times takes off ester with Folium Eucommiae, and add 1% therein, by 65% cellulase, the compound bio-enzyme preparation that 5% proteolytic enzyme and 30% polygalacturonase are formed, handled 24 o'clock, divide 2 times 40 ℃ of refluxing extraction with 4 times 40% ethanolic soln again, the 1st time 0.5 hour, the 2nd time 0.5 hour, each after-filtration that extracts, merging filtrate adds 3% in filtrate, by 90% Sulfothiorine, the composite reduction solvent that 10% sodium bisulfite is formed, and filtrate liquid concentrated the back transfer pH to 2 with concentrated hydrochloric acid, add 3 times of ethyl acetate extractions 2 times, ethyl acetate layer.Add the neutralization of 3%NaOH liquid, water separates out chlorogenic acid with concentrated hydrochloric acid acid again, separates the back with the incomplete dissolving-recrystallization of a spot of ethyl acetate, is drying to obtain the chlorogenic acid crude product.With the solid-liquid ratio of chlorogenic acid crude product with 1:4, keep malleation at the high pure nitrogen that feeds 99.99% continuously, pressure reduction〉under the condition of 5Pa, add 10% gac backflow 0.5 hour, filtration, crystallisation by cooling in water, crystallization is 99.25% high-purity chlorogenic acid with 0.5 times the cleaning of analytical pure acetone, vacuum-drying acquisition content.
Embodiment 2: a kind of technique for producing high purity chlorogenic acid in industrialization scale, it is the Folium Eucommiae that to pulverize, sherwood oil with 2 times takes off ester with Folium Eucommiae, and add 1% therein, by 45% cellulase, 10% proteolytic enzyme and 45% polygalacturonase are formed the compound bio-enzyme preparation, handled 28 o'clock, divide 2 times 45 ℃ of refluxing extraction with 6 times 50% ethanolic soln again, the 2nd time 0.5 hour, the 2nd time 1 hour, each after-filtration that extracts, merging filtrate adds 3% in filtrate, by 85% Sulfothiorine, the composite reduction solvent that 15% sodium bisulfite is formed, and filtrate liquid concentrated the back transfer pH to 2.5 with concentrated hydrochloric acid, add 3 times of ethyl acetate extractions 2 times, ethyl acetate layer.Add the neutralization of 4% NaOH liquid, water separates out chlorogenic acid with concentrated hydrochloric acid acid again, separates the back with the incomplete dissolving-recrystallization of a spot of ethyl acetate, is drying to obtain the chlorogenic acid crude product.With the solid-liquid ratio of chlorogenic acid crude product with 1:5, keep malleation at the high pure nitrogen that feeds 99.99% continuously, pressure reduction〉under the condition of 5Pa, add 10% gac backflow 0.5 hour, filtration, crystallisation by cooling in water, crystallization is 99.76% high-purity chlorogenic acid with 0.5 times the cleaning of analytical pure acetone, vacuum-drying acquisition content.
Embodiment 3: a kind of technique for producing high purity chlorogenic acid in industrialization scale, it is the Folium Eucommiae that to pulverize, sherwood oil with 2 times takes off ester with Folium Eucommiae, and add 1% compound bio-enzyme preparation (identical) therein and handled 32 o'clock with embodiment 1, divide 2 times 50 ℃ of refluxing extraction with 6 times 60% ethanolic soln again, the 1st time 1 hour, the 2nd time 1 hour, each after-filtration that extracts, merging filtrate adds 3% in filtrate, by 85% Sulfothiorine, the composite reduction solvent that 15% sodium bisulfite is formed, filtrate liquid is concentrated the back transfer pH to 3, add 3 times of ethyl acetate extractions 2 times, get ethyl acetate layer with concentrated hydrochloric acid.Add the neutralization of 5%NaOH liquid, water separates out chlorogenic acid with concentrated hydrochloric acid acid again, separates the back with the incomplete dissolving-recrystallization of a spot of ethyl acetate, is drying to obtain the chlorogenic acid crude product.With the solid-liquid ratio of chlorogenic acid crude product with 1:5, keep malleation at the high pure nitrogen that feeds 99.99% continuously, pressure reduction〉under the condition of 5Pa, add 10% gac backflow 1 hour, filtration, crystallisation by cooling in water, crystallization is 99.99% high-purity chlorogenic acid with 1 times the cleaning of analytical pure acetone, vacuum-drying acquisition content.
Embodiment 4: the technology of production is as described in the embodiment 1, and different is with 40% butanol solution as extracting solution, and obtaining chlorogenic acid content is 99.56%.
Embodiment 5: the technology of production is as described in the embodiment 2, and different is to add 1% compound bio-enzyme preparation, forms with embodiment 2, handles 36 o'clock; 4 times of ethyl acetate extractions 3 times, obtaining content is 99.52% chlorogenic acid.
Embodiment 6: production technique is as described in the embodiment 2, different is with the solid-liquid ratio of chlorogenic acid crude product with 1:3, keeps malleation, pressure reduction at the high pure nitrogen that feeds continuously 99.99%〉under the condition of 5Pa, add 8% gac and refluxed 1 hour in water, obtaining content is 99.7% chlorogenic acid.
Embodiment 7: the technology of production is as described in the embodiment 3, and different is to add 3%, and by the composite reduction solvent that 95% Sulfothiorine, 5% sodium bisulfite are formed, acquisition content is 99.89% chlorogenic acid.
Claims (1)
1, a kind of technique for producing high purity chlorogenic acid in industrialization scale is characterized in that the branch following steps finish:
1.1 pre-treatment: the Folium Eucommiae that adds after the pulverizing takes off ester with 2 times sherwood oil with Folium Eucommiae, and adding 1% therein, the compound bio-enzyme preparation of being made up of 45%-65% cellulase, 5%-10% proteolytic enzyme and 30%-45% polygalacturonase is also put into airtight window and is stored 24-36 hour;
1.2 extract: with 4-5 times of Folium Eucommiae weight, concentration is ethanol or the butanols of 40%-60%, extracts 0.5-1 hour under 40 ℃ of-50 ℃ of temperature, extracts twice with identical condition, centrifuging and squeezing;
1.3 purify: in extracting solution, add 2%-3% composite reduction solvent, described composite reduction solvent is made up of 85%-95% Sulfothiorine and 5%-15% sodium bisulfite, extracting solution is concentrated the back transfer pH to 2-3 with concentrated hydrochloric acid, with twice of concentrated solution 3-4 ethyl acetate extraction doubly, get ethyl acetate layer, wherein adding the neutralization of 3%-5%NaOH liquid makes the chlorogenic acid in the ethyl acetate enter water, separate out the chlorogenic acid precipitation with concentrated hydrochloric acid acid again after the aqueous phase separation, after the precipitate and separate with the incomplete dissolving-recrystallization of a spot of ethyl acetate, be drying to obtain the chlorogenic acid crude product, content is generally about 95%-98%, extraction yield about 2.7%;
1.4 finished product is refining: chlorogenic acid crude product and deionized water are with the solid-liquid ratio of 1:3 or 1:4, keep malleation at the high pure nitrogen that feeds 99.99% continuously, pressure reduction〉under the condition of 5Pa, dissolving also adds the 8%-10% gac and is heated to 50-60 ℃ of backflow 0.5-1 hour, filtration, crystallisation by cooling, crystallization with 2-5 analytical pure acetone doubly clean, vacuum-drying obtains 99% above high-purity chlorogenic acid.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101157827B (en) * | 2007-09-27 | 2014-03-05 | 贵州大学 | Method for extracting filament gutta-percha from eucommia leaf and skin |
| CN101486651B (en) * | 2009-02-10 | 2012-05-09 | 江苏省苏微微生物研究有限公司 | Method for extracting chlorogenic acid from Eucommia leaves and use thereof |
| CN101805261A (en) * | 2010-03-26 | 2010-08-18 | 汉中天然谷生物科技有限公司 | Method for preparing competitive product of chlorogenic acid by folium cortex eucommiae |
| CN102476997B (en) * | 2010-11-23 | 2014-04-02 | 陕西理工学院 | Method for preparing chlorogenic acid by freezing, concentrating and crystallizing |
| CN102687777A (en) * | 2011-03-24 | 2012-09-26 | 湖北太阳峰生物科技有限公司 | Preparation method of eucommia green tea powder |
| CN103535727A (en) * | 2013-10-23 | 2014-01-29 | 蒙思瑾 | Preparation method of blood pressure reducing electuary |
| CN103815141B (en) * | 2014-01-22 | 2016-06-01 | 吉首大学 | Folium Eucommiae fodder additives and its preparation method |
| CN103798520B (en) * | 2014-01-22 | 2016-08-24 | 吉首大学 | A kind of feed additive of substitute antibiotics and preparation method thereof |
| PL224631B1 (en) | 2014-05-23 | 2017-01-31 | Bartłomiej Kożniewski | Method for the synthesis of monocaffeoylquinic or dicaffeoylquinic acid isomer |
| CN110240544B (en) * | 2019-06-03 | 2021-02-09 | 西北农林科技大学 | Chlorogenic acid extraction and purification method and application |
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| 酶法提取杜仲叶活性成分的研究. 罗季阳等.食品科学，第26卷第1期. 2005 |
| 酶法提取杜仲叶活性成分的研究. 罗季阳等.食品科学，第26卷第1期. 2005 * |
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Owner name: SICHUAN JIUZHANG BIOLOGICAL TECHNOLOGY CO., LTD. Free format text: FORMER NAME: JIUZHANG BIO-CHEMICAL ENGINEERING TECH. + SCIENCE DEVELOPMENT CO., LTD., SICHUAN |
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Address after: 610041 Sichuan high tech Zone, Chengdu Province Park, No. two South Road, No. 10 Patentee after: SICHUAN JIUZHANG BIOTECHNOLOGY CO., LTD. Address before: 610041 Sichuan high tech Zone, Chengdu Province Park, No. two South Road, No. 10 Patentee before: Jiuzhang Bio-Chemical Engineering Tech. & Science Development Co., Ltd., Sichuan |
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