CN101024609B - Process for producing shikimic acid - Google Patents
Process for producing shikimic acid Download PDFInfo
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- CN101024609B CN101024609B CN2007100211500A CN200710021150A CN101024609B CN 101024609 B CN101024609 B CN 101024609B CN 2007100211500 A CN2007100211500 A CN 2007100211500A CN 200710021150 A CN200710021150 A CN 200710021150A CN 101024609 B CN101024609 B CN 101024609B
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- shikimic acid
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- silica gel
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Abstract
The invention supplies a shikimic acid producing method that includes the following steps: adding water into raw material chinese anise, taking recycling for 6-8 hours at 50-80 degree centigrade, concentrating to skikimic acid extractive raw material; mixing and whisking raw material and silica gel according to 1:1, leaching by ethyl acetate, testing and collecting eluate, concentrating and filtering to gain shikimic primary crystallization, taking recrystallization by using the same method. The invention sharply simplifies distilling process, improves working efficiency, decreases producing cost, and could shikimic acid of 90-95% purity.
Description
Technical field
The present invention relates to a kind of production technique of convenient shikimic acid, especially a kind of method of from plant, directly extracting shikimic acid.
Background technology
Shikimic acid is a kind of ring-type organic acid that is present in natural phant such as star anise and some gymnosperms, and it is the main active ingredient in the Chinese medicine Magnoliacea plant star anise.Show that through years of researches it has thrombus, analgesia and the intermediate that is used as chemosynthesis such as antitumor, shikimic acid not only is usually used in easing pain, anticancer and antithrombotic reagent, also is used for synthetic pesticide and antiseptic-germicide.Along with bird flu is in recent years starved generally popularly global, natural shikimic acid becomes the essential raw material of human bird flu-----Tamiflu of synthetic anti-curing the disease property of height, and is favourably welcome, and a price soars.China is the major production areas of star anise in the world, and the star anise of the whole world more than 80% originates from China, provides abundant fine raw material sources for we extract natural shikimic acid.
Though both at home and abroad all in the new technology of the synthetic shikimic acid of exploitation, from anise, extract this composition and be still the main path of producing Tamiflu at present.The production technique of existing shikimic acid mainly is to adopt traditional multiple organic solvent lixiviate method of purification.Summarizing to get up traditional technological process is mainly: with organic solvents such as sherwood oil, ethyl acetate, normal hexanes star anise dry powder is carried out degreasing, the raw material slag is used alcohol reflux again, the medicinal extract of gained dissolves and removal of impurities successively with several different organic solvents in succession, afterwards with single solvent or mixed solvent crystallization, and then, obtain the shikimic acid elaboration with single solvent or mixed solvent recrystallization repeatedly.This traditional production technique in production practice, exist many be difficult to overcome but have to the problem that runs into again in process of production: the one, all bigger organic solvent of gained medicinal extract viscosity is difficult to be penetrated in the medicinal extract liquid and influences impurity-eliminating effect, also than being easier to emulsion; The 2nd, in leaching process, to use multiple different organic solvent, not only technological process is tediously long, improved production cost, and bring very big potential safety hazard, repeatedly use different organic solvents, the intersection that forms solvent is easily mixed, and causes the regeneration difficulty of solvent to increase solvent loss rate height; The 3rd, labor strength is big, increases human cost, because over-drastic production stage in process of production, raw material availability reduces, and is unfavorable for expanding the scale of production, and the purity of product is difficult to guarantee, has influenced the output of product.Therefore, existing manufacturing technique is improved and improved is extremely to be necessary and realistic meaning, and is a urgent problem.
Summary of the invention
Technical problem is to overcome the complex technical process that exists in the existing conventional art, and solvent-oil ratio is excessive, and organic solvent uses kind many, intersect and mix seriously, raw material availability is low, the cost height, the not high shortcoming of working efficiency the invention provides a kind of convenient effective shikimic acid producing and manufacturing technique.
Technical scheme the present invention finishes by following technical proposal:
A kind of production technique of shikimic acid comprises:
1) the plant material star anise is placed in the diacolation jar, press material: the mass ratio of water=1: 3～5, in material, add entry, under normal pressure, heat 50～80 ℃ of circulations 6～8 hours, in the internal recycle concentration tank, be concentrated into the medicinal extract shape, obtain shikimic acid medicinal extract raw material;
2) while hot shikimic acid medicinal extract by quality than material: the mixed of silica gel=1: 1, stir, be cooled to driedly, sample introduction is crossed chromatography column to be used for feeding;
3) sample that cooling drying is stirred is loaded on chromatography column upper end 10～20cm thickness, use ethyl acetate then, shikimic acid sample to the chromatography column upper end carries out drip washing, detect the shikimic acid in the monitoring leacheate, record and contain shikimic acid in the leacheate and promptly collect leacheate, leacheate is concentrated into dried, obtains shikimic acid medicinal extract crude product;
4) shikimic acid medicinal extract crude product earlier behind 1～2 times of methyl alcohol or dissolve with ethanol with quality of material, adds 2～4 times of water of quality of material again, and the refrigeration crystallization of spending the night is filtered and obtained the shikimic acid crystallization.
Technological process specifies:
A silica gel dress post can use conventional dry method or wet method to adorn two kinds on post;
Silica gel in the B chromatography column can repeat repeatedly to use, after ethyl acetate drip washing end, can cut out silica gel (about 20cm that the upper strata is mixed with the medicinal extract sample, annotate: this layer silica gel adsorption lipid and other impurity of 85%～95%), can carry out the secondary fresh sample and stir the silica gel upper prop, so can recycle in the chromatography column silica gel 5～6 times; Improve the utilization ratio of silica gel, saved production cost;
C detects monitoring method to effective constituent shikimic acid in the leacheate, detect the leacheate that flows out with the high performance liquid phase detector, it is air-dry to get 1 milliliter of leacheate, 1～2 times of dissolve with ethanol sample introduction with quality of material, monitoring time is spaced apart 30～60 minutes, records to contain shikimic acid in the leacheate and just begin to collect.Testing conditions is moving phase is transferred pH value to 2 with phosphoric acid a redistilled water; Flow velocity is 0.6ml/min; Wavelength: 213nm; 25 ℃ of column temperatures; Chromatographic column C18; Sample size 20 microlitres; Contrast concentration 20 mcg/ml,
D can carry out the ethyl acetate pipe production in the technology of carrying out chromatography column.
Beneficial effect the present invention compared with prior art has following advantage and effect:
Adopt the present invention program, promptly adopt the flooding of circulation heating easily star anise to obtain the shikimic acid medicinal extract crude product (making full use of shikimic acid characteristic soluble in water) of the overwhelming majority, stir silica gel then and cross chromatography column, collect the new shikimic acid extraction process of effective constituent, it is various fundamentally to have solved the technological process step of using various organic solvents gradation removal of impurities to exist in the existing traditional technology, the organic solvent usage quantity is excessive, kind is many, the solvent crossed contamination, recovery utilization rate is low, consuming time expending, problem such as quality is not good enough, one step water is carried concentrated extract, chromatography is spent post two step and can be obtained the pure product of 90～95% shikimic acids then, thereby has simplified a large amount of uses that the extraction process process has been saved the high price organic solvent greatly, has improved working efficiency, reduced production cost, alleviated working strength of workers, cut the yield height, quality better active constituent content height, can access the pure product shikimic acid between 90～95%, and can comparatively produce under the simple and crude equipment condition.
The technological difficulties that the present invention solves are: in ethyl acetate drip washing chromatography column process, should reasonably monitor and carry out the collection of effective leacheate to effective constituent shikimic acid in the leacheate.The whole mistake in the post technological process only used a kind of organic solvent----ethyl acetate of routine, avoided the intersection mixing of different organic solvents in the production process, also simplified operating process simultaneously; Be leacheate owing to having adopted ethyl acetate simultaneously, thereby make the enrichment degree of shikimic acid very high, whole chromatography process time weak point is 5～7 hours, is convenient to carry out production monitoring.
Can carry out pipe production in the technology of carrying out chromatography column, so can reduce the loss through volatilization of ethyl acetate, can reduce production costs, be convenient to manufacturing enterprise's standard and produce.
In addition, the inventor of this patent has obtained the success of carrying out canalization scale operation, can carry out stably manufactured, obtains large batch of highly purified elaboration shikimic acid, and the final yield of shikimic acid has reached more than 85% in big process of producing.
Embodiment
Embodiment 1
1500kg star anise dry fruit (shikimic acid content is 3.69%) was crushed to 20～30 purpose granularities and placed the diacolation jar, press material: water=1: 3 mass ratio, water is fed in the material, and heating water temperature to 75 ℃ immersion material is 1 hour under normal pressure, opens motor cycle 15 minutes, soaked again 1 hour, so repeat .5 time, soak and extract after 7 hours, in the internal recycle concentration tank behind the concentrated percolate, getting proportion is 1.15, and weight is the shikimic acid crude product medicinal extract of 45.7kg.
2 press material to shikimic acid crude product medicinal extract while hot: silica gel=1: 1 mixed, stir, and be cooled to driedly, the sample introduction that is used for feeding is crossed chromatography column.
The chromatography column upper end that it is 40cm that the 3 silica gel samples that cooling drying is stirred are loaded on 6 internal diameters respectively, thickness of sample is about 15cm, use the leacheate of single component-----ethyl acetate then, the shikimic acid sample on the chromatography column is carried out drip washing, flow velocity is about 800ml/min.
4 usefulness high performance liquid phase detectors detect the leacheate flow out, wait to record to contain shikimic acid in the leacheate and just begin to collect, and have collected through 5 hours, and are dated especially: as to have realized the ethyl acetate pipeline in this process, cyclical operation.The shikimic acid testing conditions is a moving phase: the redistilled water of transferring pH value to 2 with phosphoric acid; Flow velocity: 0.6ml/mi n; Wavelength: 213nm; 25 ℃ of column temperatures; Chromatographic column C18; Sample size 20 microlitres; Contrast concentration 20 mcg/ml.
5 concentrate collection liquid to doing, and add the 15L dissolve with methanol, add 45L water then, leave standstill the refrigeration crystallization, filter crystal next day and get the pure product 18kg of dry shikimic acid, and detection level is 92%.
The identical crystallization method recrystallization of 6 usefulness steps 5 once, content is 98% elaboration shikimic acid 16kg, the final extraction yield of shikimic acid is 85%.
Embodiment 2
150kg star anise dry fruit (content is 3.69%) was crushed to 20～30 purpose granularities and placed the diacolation jar, press material: solvent=1: 3 mass ratio, water is fed in the material, and heating water temperature to 75 ℃ immersion material is 1 hour under normal pressure, opens motor cycle 15 minutes, soaked again 1 hour, so repeat 5 times, soak and extract after 7 hours, in the internal recycle concentration tank, concentrate percolate after, getting proportion is 1.15, and weight is the shikimic acid crude product medicinal extract of 5.7kg.
2 press material to shikimic acid crude product medicinal extract while hot: silica gel=1:1 mixed, stir, and be cooled to driedly, cross chromatography column with this sample introduction that is used for feeding.
The chromatography column upper end that it is 40cm that the 3 silica gel samples that cooling drying is stirred are loaded on 1 internal diameter respectively, thickness of sample is about 10cm, use the leacheate of single component-----ethyl acetate then, the shikimic acid sample on the chromatography column is carried out drip washing, flow velocity is about 800ml/min.
4 usefulness high performance liquid phase detectors detect the leacheate flow out, wait to record to contain shikimic acid in the leacheate and just begin to collect, through collecting (dated especially: as to have realized the ethyl acetate pipeline in this process, cyclical operation) in 5 hours.
5 concentrate collection liquid to doing, and add the lL dissolve with methanol, add 4L water then, leave standstill refrigeration acquisition crystallization, filter crystal next day and get the pure product 1.85kg of dry shikimic acid, and detection level is 91%.
The identical crystallization method recrystallization of 6 usefulness step 5) once, content is 99% elaboration shikimic acid 1.50kg, the final extraction yield of shikimic acid is 81%.
Embodiment 3
1200kg star anise dry fruit (content is 3.69%) was crushed to 20～30 purpose granularities and placed the diacolation jar, press material: solvent=1: 3 mass ratio, water is fed in the material, and the heating water temperature was soaked material 1 hour to 75C under normal pressure, opened motor cycle 15 minutes, soaked again 1 hour, so repeat 5 times, soak and extract after 7 hours, in the internal recycle concentration tank, concentrate percolate after, getting proportion is 1.15, and weight is the shikimic acid crude product medicinal extract of 20.2kg.
2 press material to shikimic acid crude product medicinal extract while hot: silica gel=1: 1 mixed, stir, and be cooled to driedly, the sample introduction that is used for feeding is crossed chromatography column.
The chromatography column upper end that it is 40cm that the 3 silica gel samples that cooling drying is stirred are loaded on 3 internal diameters respectively, thickness of sample is about 12cm, use the leacheate of single component-----ethyl acetate then, the shikimic acid sample on the chromatography column is carried out drip washing, flow velocity is about 800ml/min.
4 usefulness high performance liquid phase detectors detect the leacheate flow out, wait to record to contain shikimic acid in the leacheate and just begin to collect, through collecting (dated especially: as to have realized the ethyl acetate pipeline in this process, cyclical operation) in 5 hours.
5 concentrate collection liquid to doing, and add the 1L dissolve with methanol, add 4L water then, leave standstill the refrigeration crystallization, filter crystal next day and get the pure product 6.9kg of dry shikimic acid, and detection level is 90%.
The identical crystallization method recrystallization of 6 usefulness once, content is 97% elaboration shikimic acid 6.62kg, the final extraction yield of shikimic acid is 87%.
Embodiment 4
1100kg star anise dry fruit (content is 3.69%) was crushed to 20～30 purpose granularities and placed the diacolation jar, press material: solvent=1: 3 mass ratio, water is fed in the material, and heating water temperature to 75 ℃ immersion material is 1 hour under normal pressure, opens motor cycle 15 minutes, soaked again 1 hour, so repeat 5 times, soak and extract after 7 hours, in the internal recycle concentration tank, concentrate percolate after, getting proportion is 1.15, and weight is the shikimic acid crude product medicinal extract of 12.2kg.
2 press material to shikimic acid crude product medicinal extract while hot: silica gel=1: 1 mixed, stir, and be cooled to driedly, cross chromatography column with 1 sample introduction that is used for feeding.
The chromatography column upper end that it is 40cm that the 3 silica gel samples that cooling drying is stirred are loaded on 2 internal diameters respectively, thickness of sample is about 15cm, use the leacheate of single component-----ethyl acetate then, the shikimic acid sample on the chromatography column is carried out drip washing, flow velocity is about 800ml/min.
4 usefulness high performance liquid phase detectors detect the leacheate flow out, wait to record to contain shikimic acid in the leacheate and just begin to collect, through collecting (dated especially: as to have realized the ethyl acetate pipeline in this process, cyclical operation) in 5 hours.
5 concentrate collection liquid to doing, and add the 1L dissolve with methanol, add 4L water then, leave standstill the refrigeration crystallization, filter crystal next day and get the pure product 3.8kg of dry shikimic acid, and detection level is 93%.
The identical crystallization method recrystallization of 6 usefulness once, content is 98% elaboration shikimic acid 3.2kg, the final extraction yield of shikimic acid is 85%.
Claims (3)
1. the production technique of a shikimic acid comprises the following steps:
1) the plant material star anise is placed in the diacolation jar, press material: the mass ratio of water=1: 3～5, in material, add entry, under normal pressure, heat 50～80 ℃ of circulations 6～8 hours, in the internal recycle concentration tank, be concentrated into the medicinal extract shape, obtain shikimic acid medicinal extract raw material;
2) while hot shikimic acid medicinal extract by quality than material: the mixed of silica gel=1: 1, stir, be cooled to driedly, sample introduction is crossed chromatography column to be used for feeding;
3) sample that cooling drying is stirred is loaded on chromatography column upper end 10～20cm thickness, use ethyl acetate then, shikimic acid sample to the chromatography column upper end carries out drip washing, detect the shikimic acid in the monitoring leacheate, record and contain shikimic acid in the leacheate and promptly collect leacheate, leacheate is concentrated into dried, obtains shikimic acid medicinal extract crude product;
4) shikimic acid medicinal extract crude product earlier behind 1～2 times of methyl alcohol or dissolve with ethanol with quality of material, adds 2～4 times of water of quality of material again, and the refrigeration crystallization of spending the night is filtered and obtained the shikimic acid crystallization.
2. according to the production technique of the described a kind of shikimic acid of claim 1, it is characterized in that: silica gel dress post is that dry method or wet method are adorned two kinds on post, silica gel in the chromatography column repeats repeatedly to use, after ethyl acetate drip washing finishes for the first time, cut out the silica gel 20cm that the upper strata is mixed with the medicinal extract sample, carry out the secondary fresh sample and stir the silica gel upper prop, so can recycle in the chromatography column silica gel 5～6 times.
3. according to the production technique of claim 1 or 2 described a kind of shikimic acids, it is characterized in that: effective constituent shikimic acid in the leacheate is detected monitoring method is, detect the leacheate that flows out with the high performance liquid phase detector, it is air-dry to get 1 milliliter of leacheate, 1～2 times of dissolve with ethanol sample introduction with quality of material, monitoring time is spaced apart 30～60 minutes, records to contain shikimic acid in the leacheate and just begin to collect, and testing conditions is moving phase is transferred pH value to 2 with phosphoric acid a redistilled water; Flow velocity is 0.6ml/min; Wavelength: 213nm; 25 ℃ of column temperatures; Chromatographic column C18; Sample size 20 microlitres; Contrast concentration 20 mcg/ml.
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| CN2007100211500A CN101024609B (en) | 2007-03-30 | 2007-03-30 | Process for producing shikimic acid |
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| CN2007100211500A CN101024609B (en) | 2007-03-30 | 2007-03-30 | Process for producing shikimic acid |
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| CN101024609B true CN101024609B (en) | 2010-07-07 |
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Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JP6893356B2 (en) * | 2017-08-24 | 2021-06-23 | 一般社団法人八角平和計画研究所 | How to make shikimic acid |
| CN109134238A (en) * | 2018-09-30 | 2019-01-04 | 那坡康正天然植物提取有限责任公司 | A kind of production technology for extracting shikimic acid from illiciumverum |
| CN109485559B (en) * | 2018-11-22 | 2022-02-11 | 桂林莱茵生物科技股份有限公司 | Method for extracting shikimic acid from star anise |
| CN111548265A (en) * | 2020-06-16 | 2020-08-18 | 南通科兴石墨设备有限公司 | High-efficiency shikimic acid concentration process |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1830939A (en) * | 2006-04-12 | 2006-09-13 | 刘润民 | Convenient method for producing shikimic acid |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1830939A (en) * | 2006-04-12 | 2006-09-13 | 刘润民 | Convenient method for producing shikimic acid |
Non-Patent Citations (4)
| Title |
|---|
| JP特开2002-80421A 2002.03.19 |
| JP特开2003-12470A 2003.01.15 |
| 李红玲等.小花八角果实化学成分的研究.天然产物研究与开发6 1.1994,6(1),18-22. |
| 李红玲等.小花八角果实化学成分的研究.天然产物研究与开发6 1.1994,6(1),18-22. * |
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