CN103102351A - Refining method for preparing high-purity folic acid - Google Patents
Refining method for preparing high-purity folic acid Download PDFInfo
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- CN103102351A CN103102351A CN2013100429154A CN201310042915A CN103102351A CN 103102351 A CN103102351 A CN 103102351A CN 2013100429154 A CN2013100429154 A CN 2013100429154A CN 201310042915 A CN201310042915 A CN 201310042915A CN 103102351 A CN103102351 A CN 103102351A
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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 for preparing high purity folic acid.
Background technology
A kind of water-soluble vitamin B group that folic acid (Folic acid) is comprised of pterin structure, para-amino benzoic acid base and L-glutamic acid base, also be called FA or vitamin(e) M, that Mitchell (H.K.Mitchell, 1941) extracts purifying the earliest from the leaf of spinach, therefore called after folic acid.The folic acid structure is as follows:
Present high-quality folic acid finished product domestic production producer seldom.Subject matter is that the pteroic acid impurity in folic acid is difficult to remove.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 for utilizing the acid solution dissolving folic acid crude product of the dilute sulphuric acid of concentration between 25%-35% in the molten elutriation container of acid, through elutriation, press filtration obtains sour extract with the folic acid crude product after dissolving; Utilize alkali lye to carry out the molten alkaline solution that obtains of alkali to sour extract; Utilize diluted acid to become salt refining to obtain the folic acid finished product to alkali lye.The folic acid finished product pteroic acid content that such process for purification obtains is generally in 0.6% left and right.Although this has been the best quality of doing at present, but still pteroic acid can not be removed totally fully.
Summary of the invention
In order to remove folic acid impurity, improved the purity of folic acid.We are studied the generation of folic acid and pteroic acid and character between the two.The inventor finds that pteroic acid ammonium salt and folic acid ammonium salt have certain difference on physical properties by research, and the pteroic acid ammonium salt is under certain pH conditions, and solvability is poorer than folic acid ammonium salt in water or alcohol.Utilize this to find that we have developed a process for refining.Technical problem to be solved by this invention is to provide a kind of process for purification for preparing high purity folic acid, and this process for purification is removed totally pteroic acid substantially, and the pteroic acid content in refining rear folic acid is below 0.1%.Best quality much larger than in the market folic acid.
The present invention solves the problems of the technologies described above the technical scheme that adopts: a kind of process for purification of high purity folic acid comprises the steps:
1) sour molten step: utilize the hydrochloric acid of 15%-25% with the folic acid dissolving crude product, add water in the folic acid crude product solution after dissolving to gained, blowing, centrifugal, directly dry and obtain the acid extraction thing;
2) the molten purification step of alkali: in the molten reaction vessel of alkali, make described 1) the acid extraction thing and the solvent that obtain of sour molten step, add organic alkaline solution and make pH regulator to 9.0-10.0, be heated to 65-90 ℃, add sorbent material, insulation is 0.5-2 hour under 65-90 ℃ again, and press filtration gets alkali lixiviation liquid;
3) acid adjustment crystallisation step: with described 2) the described alkali lixiviation liquid of the molten purification step gained clarification of alkali joins in the crystallization reaction container, heats to 80 ~ 90 ℃, and transferring pH with dilute hydrochloric acid is 3.0-3.5; Temperature is down to 55 ~ 60 ℃, the centrifugal folic acid finished product that gets.
In technique scheme, the molten step of described acid can be carried out in the acid treating reactor.
The concentration of the hydrochloric acid that in above-mentioned process for refining, described 1) uses in sour molten step is 18%.
In above-mentioned process for refining, described 1) in sour molten step, the folic acid crude product quality take kilogram as measure unit and with the ratio of the described hydrochloric acid that is upgraded to measure unit at 1:4.5 between 1:5.5.Preferably, the folic acid crude product quality take kilogram as measure unit and take the ratio of the described hydrochloric acid that is upgraded to measure unit as 1:5.
In above-mentioned process for refining, described 2) in the molten purification step of alkali, a kind of as in water, methyl alcohol, ethanol of the solvent that uses.。
In above-mentioned process for refining, described 2) in the molten purification step of alkali, the solvent that uses is water.
In above-mentioned process for refining, described 2) in the molten purification step of alkali, described organic bases is a kind of 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 alkaline 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 a kind of 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 calculates according to its amount with respect to the folic acid crude product, is 5%-20%.Preferably, described 2) in the molten purification step of alkali, the consumption of described sorbent material calculates according to its amount with respect to the folic acid crude product, is 20%.
The present invention compared with prior art, have following advantage: 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, pteroic acid being removed totally substantially, the pteroic acid content in refining rear folic acid is below 0.1%.Best quality much larger than in the market folic acid.
Embodiment
In order to understand better content of the present invention, be described further below in conjunction with specific embodiment.Should be understood that these embodiment only for the present invention is further described, limit the scope of the invention and be not used in.Should be understood that in addition after having read content of the present invention, the 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 18% the hydrochloric acid for preparing in advance, opens and stirs, and adds 15 kilograms of folic acid crude products.Drip 75 kilograms of deionized waters from header tank in reactor, approximately dropwised in 12 minutes.Continue to stir 10 minutes.Blowing, centrifugal, the material of the residual a small amount of bulk in the bottom of a pan rinses with centrifugal mother liquor.Directly dry, without water wash.
Add 450 kilograms of deionized waters in the reactor of another 500L, the material with acid treating under stirring joins in reactor.Drip ammoniacal liquor and transfer pH9.Heat temperature raising, repetition measurement pH value when temperature rises to 85 ℃ after pH is stable, adds 3 kilograms of activated carbon.Begin to count soaking time, holding temperature is 85-90 ℃.Be incubated open cycle water cooling after 1 hour.When interior temperature is chilled to 55 ℃, reaction solution is put into pressure-filtering tank, press filtration.
Press filtration gets red clear liquid, is pumped in clean 500L reactor, and heating is warming up to 80 ℃, drips 10% hydrochloric acid accent PH3-3.5.83.5 ℃ of temperature.Repetition measurement PH begins cooling after 3-3.5.Temperature is down to 57 ℃.Be discharged to whizzer directly centrifugal, then use twice of the deionized water drip washing of 50 kilograms 35-40 ℃.
Material is put into vacuum drying oven, 80 ℃ of oven dry after drying.Obtain 12 kilograms of folic acid elaboration, yield: 80%.HPLC purity 99.5%, pteroic acid content 0.08%.
Embodiment 2
The reactor of 500L adds 18% the hydrochloric acid for preparing in advance, opens to stir to add 15 kilograms of folic acid crude products.Drip 75 kilograms of deionized waters from header tank in reactor, approximately dropwised in 12 minutes.Continue to stir 10 minutes.Blowing, centrifugal, the material of the residual a small amount of bulk in the bottom of a pan rinses with centrifugal mother liquor.Directly dry, without water wash.
Add 450 kilograms of methyl alcohol in the reactor of another 500L, the material with acid treating under stirring joins in reactor.Drip ammoniacal liquor and transfer PH8-9.Heat temperature raising, repetition measurement PH when temperature rises to 65 ℃, value adds 1 kilogram of diatomite after PH is stable.Begin to count soaking time, holding temperature is 65 ℃.Be incubated open cycle water cooling after 1 hour.When interior temperature is chilled to 50 ℃, reaction solution is put into pressure-filtering tank, press filtration.
Press filtration gets red clear liquid, is pumped in clean 500L reactor, and heating is warming up to 80 ℃, drips 10% hydrochloric acid accent PH3-3.5.83.5 ℃ of temperature.Repetition measurement PH begins cooling after 3-3.5.Temperature is down to 57 ℃.Be discharged to whizzer directly centrifugal.Material is put into vacuum drying oven, 80 ℃ of oven dry after drying.Get 11.2 kilograms of folic acid elaboration, yield 75%.HPLC purity 99.56%, pteroic acid content 0.06%.
Claims (9)
1. the process for purification of a high purity folic acid, is characterized in that, comprises the steps:
1) sour molten step: utilize the hydrochloric acid of 15%-25% with the folic acid dissolving crude product, add water in the folic acid crude product solution after dissolving to gained, blowing, centrifugal, directly dry and obtain the acid extraction thing;
2) the molten purification step of alkali: in the molten reaction vessel of alkali, make described 1) the acid extraction thing and the solvent that obtain of sour molten step, add organic alkaline solution and make pH regulator to 9.0-10.0, be heated to 65-90 ℃, add sorbent material, insulation is 0.5-2 hour under 65-90 ℃ again, and press filtration gets alkali lixiviation liquid;
3) acid adjustment crystallisation step: with described 2) the described alkali lixiviation liquid of the molten purification step gained clarification of alkali joins in the crystallization reaction container, heats to 80 ~ 90 ℃, and transferring pH with dilute hydrochloric acid is 3.0-3.5; Temperature is down to 55 ~ 60 ℃, the centrifugal folic acid finished product that gets.
2. the concentration of the hydrochloric acid that the process for purification of high purity folic acid as claimed in claim 1, is characterized in that, described 1) uses in sour molten 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 sour molten step, the folic acid crude product quality take kilogram as measure unit and with the ratio of the described hydrochloric acid that is upgraded to measure unit at 1:4.5 between 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, a kind of as in water, methyl alcohol, ethanol of the solvent that uses.
5. 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, the solvent that uses is water.
6. 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, described organic bases is a kind of in ammoniacal liquor, methylamine, quadrol.
7. 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, add organic alkaline solution and make pH regulator to 9.0.
8. as the process for purification of claim 1-7 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 a kind of in silica gel, activated carbon, diatomite.
9. the process for purification of high purity folic acid as claimed in claim 8, is characterized in that described 2) in the molten purification step of alkali, the consumption of described sorbent material calculates according to its amount with respect to the folic acid crude product, is 5%-20%.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104098569A (en) * | 2014-08-02 | 2014-10-15 | 济南兆康医药科技有限公司 | Medicinal folic acid purifying method |
| CN106749257A (en) * | 2017-01-19 | 2017-05-31 | 辛纪衡 | The purification process of folic acid |
| CN109232574A (en) * | 2017-07-11 | 2019-01-18 | 北京斯利安药业有限公司 | A kind of effective folic acid purification process |
| CN109265460A (en) * | 2018-12-04 | 2019-01-25 | 北京斯利安药业有限公司 | A kind of purification process of folic acid |
| CN109621860A (en) * | 2019-01-28 | 2019-04-16 | 河北冀衡（集团）药业有限公司 | A kind of synthetic method of agitating device, the reactor tank for synthesizing folic acid and folic acid |
| CN113582996A (en) * | 2021-06-02 | 2021-11-02 | 韶关市星河生物科技有限公司 | Application of hypsizigus marmoreus strain in preparation of folic acid |
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| 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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| 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 |
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Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104098569A (en) * | 2014-08-02 | 2014-10-15 | 济南兆康医药科技有限公司 | Medicinal folic acid purifying method |
| 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 |
| CN109232574A (en) * | 2017-07-11 | 2019-01-18 | 北京斯利安药业有限公司 | A kind of effective folic acid purification process |
| CN109232574B (en) * | 2017-07-11 | 2021-04-09 | 北京斯利安药业有限公司 | Effective folic acid purification method |
| CN109265460A (en) * | 2018-12-04 | 2019-01-25 | 北京斯利安药业有限公司 | A kind of purification process of folic acid |
| CN109621860A (en) * | 2019-01-28 | 2019-04-16 | 河北冀衡（集团）药业有限公司 | A kind of synthetic method of agitating device, the reactor tank for synthesizing folic acid and 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 |
| CN113582996A (en) * | 2021-06-02 | 2021-11-02 | 韶关市星河生物科技有限公司 | Application of hypsizigus marmoreus strain in preparation of folic acid |
| 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 |
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