CN103102351B - Refining method for preparing high-purity folic acid - Google Patents
Refining method for preparing high-purity folic acid Download PDFInfo
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- CN103102351B CN103102351B CN201310042915.4A CN201310042915A CN103102351B CN 103102351 B CN103102351 B CN 103102351B CN 201310042915 A CN201310042915 A CN 201310042915A CN 103102351 B CN103102351 B CN 103102351B
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Abstract
The invention discloses a refining method for preparing high-purity folic acid. The method comprises the following steps: 1) dissolving acid, namely dissolving coarse folic acid by utilizing 15-25 percent of hydrochloric acid, adding water into the dissolved coarse folic acid solution, discharging, centrifuging, and directly drying to obtain an acid extract; 2) alkali dissolution refining, namely mixing the acid extract obtained in the acid dissolution step (1) and a solvent, adding an organic alkali solution to regulate the pH value to be 9.0-10.0, heating and raising the temperature to be 65-90 DEG C, adding an adsorbent, keeping the temperature at the temperature of 65-90 DEG C for 0.5-2 hours, and performing filter pressing to obtain alkali-soluble filtrate; and 3) regulating acid crystallization, namely adding the clarified alkali solution filtrate obtained in the alkali dissolution refining 2) into a crystallization reaction container, heating and raising the temperature to be 80-90 DEG C, regulating the pH value to be 3.0-3.5 by using diluted hydrochloric acid, reducing the temperature to be 55-60 DEG C, and centrifuging to obtain a finished folic acid product.
Description
Technical field
The present invention relates to medical extractive technique field, particularly relate to a kind of process for purification preparing high-purity folic acid.
Background technology
A kind of water-soluble B vitamin that folic acid (Folic acid) is made up of pterin structure, para-amino benzoic acid base and L-glutamic acid base, also FA or vitamin(e) M is called, Mitchell (H.K.Mitchell, 1941) extraction purification from the leaf of spinach the earliest, therefore called after folic acid.Folic acid structure is as follows:
Current high-quality folic acid finished product domestic production producer is little.Subject matter is that the pteroic acid impurity in folic acid is difficult to removing.Its pteroic acid content is again the important indicator of folic acid outgoing quality.
Its pteroic acid structural formula is as follows:
Existing folic acid process for purification (Chinese patent CN102432610A) is in acid-soluble elutriation container, utilize the acid solution of the dilute sulphuric acid of concentration between 25%-35% to dissolve folic acid crude product, and by the folic acid crude product after dissolving through elutriation, press filtration obtains sour extract; Alkali is molten obtains alkaline solution to utilize alkali lye to carry out sour extract; Diluted acid is utilized to become salt refining to obtain folic acid finished product to alkali lye.The folic acid finished product pteroic acid content that such process for purification obtains is generally about 0.6%.Although this has been the best quality done at present, but still pteroic acid can not be removed completely clean.
Summary of the invention
In order to remove folic acid impurity, improve the purity of folic acid.We are studied the generation of folic acid and pteroic acid and character between the two.By research, the present inventor finds that pteroic acid ammonium salt and folic acid ammonium salt have certain difference in physical properties, and pteroic acid ammonium salt is under certain pH conditions, and in water or alcohol, solvability is poorer than folic acid ammonium salt.This discovery is utilized to we have developed a process for refining.Technical problem to be solved by this invention is to provide a kind of process for purification preparing high-purity folic acid, and this process for purification makes pteroic acid substantially remove totally, and the pteroic acid content after refining in folic acid is below 0.1%.Much larger than the best quality of folic acid in the market.
The present invention solves the problems of the technologies described above adopted technical scheme: a kind of process for purification of high-purity folic acid, comprises the steps:
1) acid-soluble step: utilize the hydrochloric acid of 15%-25% by folic acid dissolving crude product, adds water in the folic acid crude product solution after dissolving to gained, and blowing is centrifugal, directly dries and obtains acid extraction thing;
2) the molten purification step of alkali: in the molten reaction vessel of alkali, make described 1) the acid extraction thing that obtains of acid-soluble step and solvent, add organic alkali solution and make pH regulator to 9.0-10.0, be heated to 65-90 DEG C, add sorbent material again, be incubated 0.5-2 hour at 65-90 DEG C, press filtration obtains alkali lixiviation liquid;
3) acid adjustment crystallisation step: by described 2) alkali molten purification step gained clarification described alkali lixiviation liquid join in crystallization reaction container, heat to 80 ~ 90 DEG C, with dilute hydrochloric acid adjust pH be 3.0-3.5; Temperature is down to 55 ~ 60 DEG C, centrifugal folic acid finished product.
In technique scheme, described acid-soluble step can be carried out in acid treating reactor.
In above-mentioned process for refining, described 1) concentration of the hydrochloric acid used in acid-soluble step is 18%.
In above-mentioned process for refining, described 1) in acid-soluble step, with kilogram for the folic acid crude product quality of measure unit and with the ratio of the described hydrochloric acid being upgraded to measure unit between 1:4.5 to 1:5.5.Preferably, with kilogram for the folic acid crude product quality of measure unit and with the ratio of the described hydrochloric acid being upgraded to measure unit for 1:5.
In above-mentioned process for refining, described 2) in the molten purification step of alkali, the solvent used is water, one in methyl alcohol, ethanol.。
In above-mentioned process for refining, described 2), in the molten purification step of alkali, the solvent used is water.
In above-mentioned process for refining, described 2), in the molten purification step of alkali, described organic bases is the one in ammoniacal liquor, methylamine, quadrol.Preferably, described organic bases is ammoniacal liquor.
In above-mentioned process for refining, described 2), in the molten purification step of alkali, add organic alkali solution and make pH regulator to 9.0.
In above-mentioned process for refining, described 2), in the molten purification step of alkali, described sorbent material is the one in silica gel, activated carbon, diatomite.
In above-mentioned process for refining, described 2), in the molten purification step of alkali, the consumption of described sorbent material is calculated according to its gauge relative to folic acid crude product, is 5%-20%.Preferably, described 2), in the molten purification step of alkali, the consumption of described sorbent material is calculated according to its gauge relative to folic acid crude product, is 20%.
The present invention compared with prior art, tool has the following advantages: the present invention adopts certain density diluted hydrochloric acid dissolution folic acid crude product, and according to the molten refining and acid adjustment crystallization of alkali that certain technique is carried out, make pteroic acid substantially remove totally, the pteroic acid content after refining in folic acid is below 0.1%.Much larger than the best quality of folic acid in the market.
Embodiment
In order to understand content of the present invention better, be described further below in conjunction with specific embodiment.Should be understood that these embodiments only for the present invention is further described, and be not used in and limit the scope of the invention.In addition should be understood that, after having read content of the present invention, person skilled in art makes some nonessential change or adjustment to the present invention, still belongs to protection scope of the present invention.
Embodiment 1
The reactor of 500L, adds the hydrochloric acid of prepare in advance 18%, opens and stirs, add 15 kilograms of folic acid crude products.From header tank, drip 75 kilograms of deionized waters in reactor, within about 12 minutes, dropwise.Continue stirring 10 minutes.Blowing, centrifugal, the bottom of a pan remains a small amount of block material, rinses with centrifugal mother liquor.Direct drying, without water wash.
In the reactor of another 500L, add deionized water 450 kilograms, under stirring, the material of acid treating is joined in reactor.Drip ammoniacal liquor and adjust pH9.Heat temperature raising, repetition measurement pH value when temperature rises to 85 DEG C, after pH is stable, adds 3 kilograms of activated carbon.Start to count soaking time, holding temperature is 85-90 DEG C.Be incubated open cycle water cooling after 1 hour.When interior temperature is chilled to 55 DEG C, reaction solution is put into pressure-filtering tank, press filtration.
Press filtration obtains red clear liquid, is pumped in clean 500L reactor, and heating, is warming up to 80 DEG C, and the hydrochloric acid dripping 10% adjusts PH3-3.5.Temperature 83.5 DEG C.Repetition measurement PH, after 3-3.5, starts cooling.Temperature is down to 57 DEG C.Be discharged to whizzer directly centrifugal, then use the deionized water drip washing twice of 50 kilograms 35-40 DEG C.
Material puts into vacuum drying oven, 80 DEG C of oven dry after drying.Obtain folic acid fine work 12 kilograms, yield: 80%.HPLC purity 99.5%, pteroic acid content 0.08%.
Embodiment 2
The reactor of 500L, adds the hydrochloric acid of prepare in advance 18%, opens stirring and adds 15 kilograms of folic acid crude products.From header tank, drip 75 kilograms of deionized waters in reactor, within about 12 minutes, dropwise.Continue stirring 10 minutes.Blowing, centrifugal, the bottom of a pan remains a small amount of block material, rinses with centrifugal mother liquor.Direct drying, without water wash.
In the reactor of another 500L, add methyl alcohol 450 kilograms, under stirring, the material of acid treating is joined in reactor.Drip ammoniacal liquor and adjust PH8-9.Heat temperature raising, repetition measurement PH when temperature rises to 65 DEG C, value, after PH is stable, adds 1 kilogram of diatomite.Start to count soaking time, holding temperature is 65 DEG C.Be incubated open cycle water cooling after 1 hour.When interior temperature is chilled to 50 DEG C, reaction solution is put into pressure-filtering tank, press filtration.
Press filtration obtains red clear liquid, is pumped in clean 500L reactor, and heating, is warming up to 80 DEG C, and the hydrochloric acid dripping 10% adjusts PH3-3.5.Temperature 83.5 DEG C.Repetition measurement PH, after 3-3.5, starts cooling.Temperature is down to 57 DEG C.Be discharged to whizzer directly centrifugal.Material puts into vacuum drying oven, 80 DEG C of oven dry after drying.Obtain folic acid fine work 11.2 kilograms, yield 75%.HPLC purity 99.56%, pteroic acid content 0.06%.
Claims (6)
1. a process for purification for high-purity folic acid, is characterized in that, comprises the steps:
1) acid-soluble step: utilize the hydrochloric acid of 15%-25% by folic acid dissolving crude product, adds water in the folic acid crude product solution after dissolving to gained, and blowing is centrifugal, directly dries and obtains acid extraction thing;
2) the molten purification step of alkali: in the molten reaction vessel of alkali, make described 1) the acid extraction thing that obtains of acid-soluble step and solvent, adding organic alkali solution makes pH regulator to 9.0-10.0, be heated to 65-90 DEG C, add sorbent material again, be incubated 0.5-2 hour at 65-90 DEG C, press filtration obtains alkali lixiviation liquid; The solvent used is water, one in methyl alcohol; Described organic bases is ammoniacal liquor;
3) acid adjustment crystallisation step: by described 2) alkali molten purification step gained clarification described alkali lixiviation liquid join in crystallization reaction container, heat to 80 ~ 90 DEG C, with dilute hydrochloric acid adjust pH be 3.0-3.5; Temperature is down to 55 ~ 60 DEG C, centrifugal folic acid finished product.
2. the process for purification of high-purity folic acid as claimed in claim 1, is characterized in that, described 1) concentration of hydrochloric acid that uses in acid-soluble step is 18%.
3. the process for purification of high-purity folic acid as claimed in claim 1, is characterized in that, described 1) in acid-soluble step, with kilogram for the folic acid crude product quality of measure unit and with the ratio of the described hydrochloric acid being upgraded to measure unit between 1:4.5 to 1:5.5.
4. the process for purification of high-purity folic acid as claimed in claim 3, is characterized in that: described 2) in the molten purification step of alkali, add organic alkali solution and make pH regulator to 9.0.
5., as the process for purification of claim 1-3 high-purity folic acid as described in any one, it is characterized in that: described 2) in the molten purification step of alkali, described sorbent material is the one in silica gel, activated carbon, diatomite.
6. the process for purification of high-purity folic acid as claimed in claim 6, is characterized in that, described 2) in the molten purification step of alkali, the consumption of described sorbent material is calculated according to its gauge relative to folic acid crude product, is 5%-20%.
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Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104098569B (en) * | 2014-08-02 | 2016-05-11 | 济南康和医药科技有限公司 | A kind of purification process of medicinal folic acid |
| CN106749257A (en) * | 2017-01-19 | 2017-05-31 | 辛纪衡 | The purification process of folic acid |
| CN109232574B (en) * | 2017-07-11 | 2021-04-09 | 北京斯利安药业有限公司 | Effective folic acid purification method |
| CN109265460B (en) * | 2018-12-04 | 2020-08-11 | 北京斯利安药业有限公司 | Purification method of folic acid |
| CN109621860B (en) * | 2019-01-28 | 2024-04-12 | 河北冀衡药业股份有限公司 | Stirring device, reaction tank for synthesizing folic acid and folic acid synthesizing method |
| CN113582996B (en) * | 2021-06-02 | 2024-02-06 | 韶关市星河生物科技有限公司 | Application of hypsizigus marmoreus strain in preparation of folic acid |
Citations (3)
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| CN101323614A (en) * | 2008-07-29 | 2008-12-17 | 河北冀衡（集团）药业有限公司 | Acidum folicum production method without sewerage discharge |
| CN101973995A (en) * | 2010-07-20 | 2011-02-16 | 上海华理生物医药有限公司 | Method for recycling waste water in production of folic acid |
| CN102432610A (en) * | 2011-09-29 | 2012-05-02 | 河北冀衡（集团）药业有限公司 | Folic acid production method for controlling content of technical pteroic acid |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101323614A (en) * | 2008-07-29 | 2008-12-17 | 河北冀衡（集团）药业有限公司 | Acidum folicum production method without sewerage discharge |
| CN101973995A (en) * | 2010-07-20 | 2011-02-16 | 上海华理生物医药有限公司 | Method for recycling waste water in production of folic acid |
| CN102432610A (en) * | 2011-09-29 | 2012-05-02 | 河北冀衡（集团）药业有限公司 | Folic acid production method for controlling content of technical pteroic acid |
Non-Patent Citations (1)
| Title |
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| 叶酸精制工艺的改进;谢振华;《江苏化工》;20050630;第33卷(第3期);第37-39页 * |
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