CN101759557A - Preparation method of shikimic acid - Google Patents
Preparation method of shikimic acid Download PDFInfo
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- CN101759557A CN101759557A CN200910234064A CN200910234064A CN101759557A CN 101759557 A CN101759557 A CN 101759557A CN 200910234064 A CN200910234064 A CN 200910234064A CN 200910234064 A CN200910234064 A CN 200910234064A CN 101759557 A CN101759557 A CN 101759557A
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Abstract
The invention relates to a method for purifying shikimic acid by water extraction, membrane separation, ion exchange resin absorption enrichment, graphite concentrator concentration and recrystallization. The method solves the problems of excessive sorts and difficult recycling of organic reagent, small resin exchange capacity, low concentration capacity of glass concentrators and easy erosion of stainless steel concentrators. The method has the advantages of short cycle, high yield and low cost when used in shikimic acid production, and easily realizes industrialization.
Description
Technical field:
The present invention relates to the extraction and purification process of shikimic acid, particularly a kind of method of using membrane technique separation and ion exchange resin enriching and purifying shikimic acid.
Background technology:
Shikimic acid molecular formula and molecular weight: C7H10O5 (174.15)
Physico-chemical property: the white fine powder, soluble in water, methyl alcohol, ethanol, the solubleness in water is 18g/100ml, is insoluble in chloroform, benzene and sherwood oil.185 ℃～191 ℃ of fusing points, specific rotation-180 °, smell is sad.
Shikimic acid is present in the dry mature fruit of Magnoliacea plant anise (Illicium verum Hook.f.).Anise is large exported product, is big fennel, aniseed again, and Chinese Pharmacopoeia record anise has warming YANG to expel cold, the effect of regulating QI to relieve pain, and its fruit, skin, leaf all contain abundant perfume oil, are used for rheumatism in meeting among the people.Mainly be distributed in South East Asia and America, South East Asia accounts for 80%, is main product state with China, secondly is countries and regions such as Vietnam, Cambodia, Burma, Indonesia, Philippines, Mexico, Haiti.China's cultivated area and output account for the first in the world, and Vietnam is second.Anise is distributed in Guangxi, Yunnan, three provinces and regions, Guangdong in China, and main product is in Guangxi, and anistree cultivated area is being continued to enlarge in Yunnan and Guangdong.Anise is distributed in part counties and cities in southwest, osmanthus, Gui Xi, south, Guidong and the osmanthus in Guangxi, 3,200,000 mu of total cultivated areas, about 2.8～3.2 ten thousand tons of normal year output, account for national ultimate production more than 85% and volume of world trade 50%, there is certain dominant force effect the domestic and international market.
Shikimic acid is the important source material of producing Tamiflu.Shikimic acid is present in a large amount of higher plants or the microorganism, because shikimic acid content is bigger in the fruit of Winteraceae plant, content surpasses 10%, so be used as the valuable source plant of extracting shikimic acid.Shikimic acid can also obtain by methods such as microbial fermentation, chemosynthesis except extracting from plant, and the shikimic acid of Roche Holding Ag 2/3rds is from anise, and one of its excess-three branch is obtained by a kind of Escherichia coli fermentation.From purification, biological activity and cost angle, it is anistree that the production of Tamiflu mainly relies on China.The production of initial Tamiflu is to be that starting raw material obtains through 12 steps with the quinic acid, but quinic acid costs an arm and a leg, and to have invented with the shikimic acid be that starting raw material can obtain Tamiflu through 10～16 steps to Luo Shi afterwards.
The Tamiflu of Xiao Shouing is the Tamiflu that Roche Group produces without competition in the market, and its common name is Ro 64-0796/002 (Oseltamivirphosphate), and Tamiflu was gone on the market by drugs approved by FDA in 1999, goes on the market in July, 2004 in China.Because Tamiflu is a kind of very effective treatment of influenza medication, and can significantly reduce the generation and the antibiotic use of complication (mainly being tracheae and bronchitis, pneumonia, pharyngitis etc.), thereby be one of the most frequently used medicine for the treatment of at present influenza, also be the anti-avian influenza of generally acknowledging, A (H 1 N 1) virus one of the most effective medicine.
Extract the technology of producing shikimic acid at present, be mostly petroleum ether degreasing, low-carbon alcohol is extracted or water extraction, activated carbon decolorizing, periodic crystallisation.Also there is bibliographical information to use resin absorption and membrane separating method: in " from the method for anistree extraction separation shikimic acid " (number of patent application 200610096526.X) and " method that from anise, prepares shikimic acid " (number of patent application 200610005211) disclosed method, to answer spent ion exchange resin absorption and membrane technique.There are a large amount of greases and protein-polysaccharide in the anise, only filter or the finings processing through general, can't go out, cause the resin absorption amount little, yield poorly, shikimic acid concentrates at high temperature, concentration peracidity more is strong more, to stainless steel thickener seriously corroded, concentrated solution has a large amount of metal ions to exist simultaneously, is difficult to realize crystallization.It is low to remove the macromolecular substance enrichment degree behind the simple membrane sepn, and the purifying number of times increases, and shikimic acid solubleness in water is 18g/ml, and existing membrane concentration equipment can't concentrate shikimic acid crystalline concentration at all.
Summary of the invention:
The objective of the invention is in order to provide a kind of cost low, shikimic acid purity reaches more than 98%, and yield is greater than 85%, and output is big,, be easy to realize industrialized shikimic acid extraction process.
The object of the present invention is achieved like this:
1. water extraction: anise is pulverized, added the water insulation and extract, filter;
2. membrane sepn: extracting solution is handled by ultra-filtration membrane by microfiltration membrane earlier again, collects and sees through liquid;
3. ion exchange resin absorption: seeing through liquid by the saturated absorption of resin anion(R.A) post, washing is neutral, and 4-5 times of 5-6% aqueous sodium hydroxide washes taken off, and collects elutriant;
4. desalination: above-mentioned elutriant by cationic resin column, is collected lower column liquid;
5. concentrate: above-mentioned lower column liquid concentrating under reduced pressure is placed crystallization 10-15 hour, filter coarse crystallization;
6. recrystallization: with above-mentioned coarse crystallization thing dissolve with methanol, place crystallization, be drying to obtain product.
Described raw material pulverizing granularity is 40～60 orders.
Described water is put forward condition: extract 5-6 times of water gaging with raw material weight, stirring is carried out, and temperature is controlled at 40-60 ℃, and extraction time 1-2 hour, extraction time 2-3 time.
Described ion exchange resin is: resin cation (R.C.) optional 732 or 004 * 7, resin anion(R.A) optional 717 or 201 * 7.
The optional molecular weight cut-off of described ultra-filtration membrane is the ultra-filtration membrane of 1000-3000.
Described concentrating under reduced pressure condition: the optional graphite concentrating under reduced pressure of concentration systems device, concentrated solution density is to 1.5-1.6.
Described re-crystallization step is: earlier with the methanol eddy dissolving, reconcentration is placed crystallization in 12-18 hour to the 5-6 amount of solute weight.
There is following advantage in the present invention: according to the character of shikimic acid, and 40-60 ℃ of water extraction, extraction rate is fast, and the impurity stripping is few.Macromolecular substance has been removed in the application of film system, has improved the adsorptive capacity of resin, has improved the coarse crystallization product content, has also reduced the activated carbon decolorizing operation simultaneously.The application of graphite concentrating under reduced pressure device has solved the shortcoming of membrane concentration and stainless steel thickener.
So production technique of the present invention is simple, cost is low, and shikimic acid purity reaches more than 98%, and yield is greater than 85%, and output is big, and the cycle is short, is easy to realize industrialization.
Further specify the present invention below in conjunction with embodiment, but the scope of protection of present invention is not limited to following embodiment.
Embodiment:
Embodiment 1:
Get 100kg anise (shikimic acid content 9%), pulverizing is 40 orders, adds 500L water, is heated to 50 ℃, stir and extracted 1 hour, extract twice, united extraction liquid, filter, adding the microfiltration membrane system filtration is the ultra-filtration membrane of 1000-3000 again by molecular weight cut-off, collects and sees through liquid.See through the D201 ion exchange resin column absorption that liquid adds 20L, earlier be washed till neutrality with deionized water, use the water-soluble wash-out shikimic acid of 100L5% sodium hydroxide again, collect the shikimic acid elutriant by 001 * 7 cationic resin column desalination, collect lower column liquid and be evaporated to density 1.5, place crystallization 10 hours with the graphite thickener.The filtering for crystallizing thing gets coarse crystallization 10kg, and with the dissolving of 90% methanol eddy, reclaim under reduced pressure methyl alcohol is placed crystallization 18 hours to 50L, filters, dry product 7.8kg, the content 98.5% of getting.
Embodiment 2:
Get 100kg anise (shikimic acid content 10%), pulverizing is 60 orders, adds 600L water, is heated to 40 ℃, stir and extracted 2 hours, extract twice, united extraction liquid, filter, adding the microfiltration membrane system filtration is the ultra-filtration membrane of 1000-3000 again by molecular weight cut-off, collects and sees through liquid.See through 201 * 7 ion exchange resin columns absorption that liquid adds 20L, earlier be washed till neutrality with deionized water, use the water-soluble wash-out shikimic acid of 80L6% sodium hydroxide again, collect the shikimic acid elutriant and collect the shikimic acid elutriant by 001 * 8 cationic resin column desalination, collect lower column liquid and be evaporated to density 1.6, place crystallization 15 hours with the graphite thickener.The filtering for crystallizing thing gets coarse crystallization 10.5kg, and with the dissolving of 99% methanol eddy, reclaim under reduced pressure methyl alcohol is placed crystallization 12 hours to 63L, filters, dry product 8.4kg, the content 99% of getting.
Embodiment 3:
Get 100kg anise (shikimic acid content 9%), pulverizing is 50 orders, adds 550 water, is heated to 40 ℃, stir and extracted 1 hour, extract united extraction liquid three times, filter, adding the microfiltration membrane system filtration is the ultra-filtration membrane of 1000-3000 again by molecular weight cut-off, collects and sees through liquid.See through 201 * 7 ion exchange resin columns absorption that liquid adds 20L, earlier be washed till neutrality with deionized water, use the water-soluble wash-out shikimic acid of 90L5% sodium hydroxide again, collect the shikimic acid elutriant and collect the shikimic acid elutriant by 001 * 7 cationic resin column desalination, collect lower column liquid and be evaporated to density 1.5, place crystallization 16 hours with the graphite thickener.The filtering for crystallizing thing gets coarse crystallization 10.3kg, and with the dissolving of 95% methanol eddy, reclaim under reduced pressure methyl alcohol is placed crystallization 16 hours to 60L, filters, dry product 7.8kg, the content 99% of getting.
Embodiment 4:
Get 200kg anise (shikimic acid content 9%), pulverizing is 30 orders, adds 1200 water, is heated to 50 ℃, stir and extracted 1 hour, extract united extraction liquid three times, filter, adding the microfiltration membrane system filtration is the ultra-filtration membrane of 1000-3000 again by molecular weight cut-off, collects and sees through liquid.See through 201 * 7 ion exchange resin columns absorption that liquid adds 40L, earlier be washed till neutrality with deionized water, use the water-soluble wash-out shikimic acid of 90L6% sodium hydroxide again, collect the shikimic acid elutriant and collect the shikimic acid elutriant by 001 * 7 cationic resin column desalination, collect lower column liquid and be evaporated to density 1.55, place crystallization 15 hours with the graphite thickener.The filtering for crystallizing thing gets coarse crystallization 21kg, and with the dissolving of 97% methanol eddy, reclaim under reduced pressure methyl alcohol is placed crystallization 18 hours to 120L, filters, dry product 15.4kg, the content 99% of getting.
Claims (7)
1. the preparation method of a shikimic acid is characterized in that comprising following step:
1. water extraction: anise is pulverized, added the water insulation and extract, filter;
2. membrane sepn: extracting solution is handled by ultra-filtration membrane by microfiltration membrane earlier again, collects and sees through liquid;
3. ion exchange resin absorption: seeing through liquid by the saturated absorption of resin anion(R.A) post, washing is neutral, and the 5-6% aqueous sodium hydroxide washes is taken off, and collects elutriant;
4. desalination: above-mentioned elutriant by cationic resin column, is collected lower column liquid;
5. concentrate: above-mentioned lower column liquid concentrating under reduced pressure is placed crystallization 10-15 hour, filter, get coarse crystallization;
6. recrystallization: with above-mentioned coarse crystallization 90-99% dissolve with methanol, place crystallization, be drying to obtain product.
2. according to the preparation method of the described shikimic acid of claim 1, it is characterized in that it is 40～60 orders that described water is put forward the raw material pulverizing granularity of step.
3. according to the preparation method of the described shikimic acid of claim 1, it is characterized in that described water puies forward condition and be: extract 5-6 times of water gaging with raw material weight, stirring is carried out, and temperature is controlled at 40-60 ℃, and extraction time 1-2 hour, extraction time 2-3 time.
4. according to the preparation method of the described shikimic acid of claim 1, it is characterized in that described ion exchange resin is: storng-acid cation exchange resin optional 001 * 8 or 001 * 7, the optional D201 of strongly basic anion exchange resin or 201 * 7.
5. according to the preparation method of the described shikimic acid of claim 1, it is characterized in that the optional molecular weight cut-off of described ultra-filtration membrane is the ultra-filtration membrane of 1000-3000.
6. according to the preparation method of the described shikimic acid of claim 1, it is characterized in that described concentrating under reduced pressure condition: concentration systems is a graphite concentrating under reduced pressure device, and concentrated solution density is to 1.5-1.6.
7. according to the preparation method of the described shikimic acid of claim 1, it is characterized in that described re-crystallization step is: earlier with the methanol eddy dissolving, reconcentration is placed crystallization in 12-18 hour to the 5-6 amount of solute weight.
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| CN200910234064A CN101759557A (en) | 2009-11-20 | 2009-11-20 | Preparation method of shikimic acid |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102584571A (en) * | 2011-11-21 | 2012-07-18 | 河南孟成生物药业股份有限公司 | Extraction process for shikimic acid in fermentation liquor |
| CN107652178A (en) * | 2017-10-30 | 2018-02-02 | 广西万山香料有限责任公司 | The method that shikimic acid is extracted from anise |
| CN107721848A (en) * | 2017-10-30 | 2018-02-23 | 广西万山香料有限责任公司 | A kind of method that shikimic acid is extracted from anise |
| CN110156589A (en) * | 2019-04-26 | 2019-08-23 | 桂林三叶生物科技有限责任公司 | A method of extracting shikimic acid from fresh octagonal fruit |
| CN111278799A (en) * | 2017-08-24 | 2020-06-12 | 一般社团法人八角平和计画研究所 | Process for producing shikimic acid |
| CN114436816A (en) * | 2021-12-25 | 2022-05-06 | 新疆阜丰生物科技有限公司 | Method for efficiently extracting shikimic acid by ion exchange technology |
| CN115232002A (en) * | 2022-07-14 | 2022-10-25 | 宜昌东阳光生化制药有限公司 | Method for extracting shikimic acid in full water phase |
-
2009
- 2009-11-20 CN CN200910234064A patent/CN101759557A/en active Pending
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102584571A (en) * | 2011-11-21 | 2012-07-18 | 河南孟成生物药业股份有限公司 | Extraction process for shikimic acid in fermentation liquor |
| CN111278799A (en) * | 2017-08-24 | 2020-06-12 | 一般社团法人八角平和计画研究所 | Process for producing shikimic acid |
| JP2021121631A (en) * | 2017-08-24 | 2021-08-26 | 一般社団法人八角平和計画研究所 | Method for producing shikimic acid |
| JP7058891B2 (en) | 2017-08-24 | 2022-04-25 | 一般社団法人八角平和計画研究所 | How to make shikimic acid |
| CN107652178A (en) * | 2017-10-30 | 2018-02-02 | 广西万山香料有限责任公司 | The method that shikimic acid is extracted from anise |
| CN107721848A (en) * | 2017-10-30 | 2018-02-23 | 广西万山香料有限责任公司 | A kind of method that shikimic acid is extracted from anise |
| CN107652178B (en) * | 2017-10-30 | 2021-07-27 | 广西玉蓝生物科技有限公司 | Method for extracting shikimic acid from star anise |
| CN110156589A (en) * | 2019-04-26 | 2019-08-23 | 桂林三叶生物科技有限责任公司 | A method of extracting shikimic acid from fresh octagonal fruit |
| CN114436816A (en) * | 2021-12-25 | 2022-05-06 | 新疆阜丰生物科技有限公司 | Method for efficiently extracting shikimic acid by ion exchange technology |
| CN114436816B (en) * | 2021-12-25 | 2024-05-28 | 新疆阜丰生物科技有限公司 | Method for efficiently extracting shikimic acid by ion exchange technology |
| CN115232002A (en) * | 2022-07-14 | 2022-10-25 | 宜昌东阳光生化制药有限公司 | Method for extracting shikimic acid in full water phase |
| CN115232002B (en) * | 2022-07-14 | 2023-11-28 | 宜昌东阳光生化制药有限公司 | Method for extracting shikimic acid from whole water phase |
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Application publication date: 20100630 |