CN104098569A - Medicinal folic acid purifying method - Google Patents
Medicinal folic acid purifying method Download PDFInfo
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- CN104098569A CN104098569A CN201410376142.8A CN201410376142A CN104098569A CN 104098569 A CN104098569 A CN 104098569A CN 201410376142 A CN201410376142 A CN 201410376142A CN 104098569 A CN104098569 A CN 104098569A
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- C07D475/00—Heterocyclic compounds containing pteridine ring systems
- C07D475/02—Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4
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Abstract
The invention provides a medicinal folic acid purifying method. According to the method, an acid-alkali method is systematically utilized for purifying folic acid crude products, folic acid finished products meeting pharmacopoeia standards can be prepared repetitively, folic acid purity is above 99%, and the content of pteroic acid impurities in refined folic acid is below 0.1%. The medicinal folic acid purifying method has the advantages that on one hand, the medicinal folic acid purifying method is used for refining the folic acid crude products aiming at the pteroic acid impurities difficult to remove, and is low in cost, simple and convenient to operate and easy to boost; on the other hand, purity and production efficiency of the folic acid can be improved effectively, and development and application in scale production are benefited.
Description
Technical field
The invention belongs to compound preparation field, be specifically related to a kind of purification process of medicinal folic acid.
Technical background
Folic acid (folic acid) is a kind of vitamin B group being extensively present in green vegetable fruit.Nineteen forty-one, the people such as American scholar Mitchell have found this compound with anti-anaemia effect in spinach, because this compound mainly comes from plant leaf, so called after folic acid.1945, the people such as Angier synthesized folic acid and have completed the mensuration of its structure.
Folic acid is called as vitamins B
9or Bc, its chemistry VitB11 by name.In the structure of folic acid, comprise pteridine, para-amino benzoic acid and L-glutamic acid structure.Folic acid finished product is a kind of orange-yellow crystal, is heated to 250 DEG C of decomposition.Folic acid is the necessary type organic matter in body normal activities process that sustains life, and after being absorbed, can participate in each process of vital movement by metabolism composition various active coenzyme by body.Its main application comprises: (a) participate in the synthetic of nucleic acid, promote division and the breeding of cell.(b) important component of formation oxyphorase.(c) conversion of promotion multiple amino acids.(d) supply with the important chemical substance that nerve ending generates and transmission is got excited.
The insufficiency of intake of folic acid can cause multiple corresponding deficiency disease, evidence suggests: the shortage of folic acid and newborn infant's deformity, macrocytic anemia and cardiovascular disorder have significant correlation.The shortage of folic acid also has direct or indirect relation with various diseases such as senile dementia, parasitosis, scurvy and rheumatoid arthritiss.Current research also finds, folic acid also has suitable antitumour activity, although anticancer mechanism is not clear, and being found to be us and further understanding, control of folic acid antitumour activity, and then treatment cancer provides new method and approach.In recent years, medical research also finds, folic acid also has mitigation to schizophrenia, can treat chronic atrophic gastritis, suppress segmental bronchus squamous and transform, the diseases such as the coronary sclerosis that prevention and treatment cause because of homocysteine blood and cardiac damage, myocardial infarction.
The correlated product of folic acid and folic acid has been widely used in food, medicine, feed, scientific research and chemical industry.As far back as 1998, U.S. food and Drug Administration (FDA) just implemented the folic acid strengthening regulation for grain products.United Kingdom Government or with within 2015, carry out folic acid fortified flour policy.China is also by iterative method " 7+1 " enriched nutritive flour, and folic acid is one of seven kinds of basic components wherein.According to incompletely statistics, in developing country, the related industries of folic acid and folic acid can relate to approximately 7%～9% GDP.The acquisition of folic acid at present mainly relies on chemosynthesis, and the common method of domestic production folic acid is now: N-NSC 71042, trichloroacetone and TAHMS are prepared folic acid crude product as intermediate.Folic acid is the valuable source that is related to national economy, and folic acid industrial expansion is also the important embodiment of a national strength.
At present, the ultimate production of global folic acid is about 900-1000 ton; This wherein high-purity folic acid of 5% be medicinal folic acid.And the demand of medicinal folic acid also presents the situation of cumulative year after year.The method of folic acid purifying can be divided into salt refining method and the large class of acid treating method two.
Patent US2694710 and US2634271 have introduced respectively the method for purifying folic acid, and the sample that the purification process of above-mentioned patent Introduction obtains after testing, can not meet present pharmaceutical folic acid quality standard.And existing additive method, or be to realize industrialization, or purifying cost is higher, therefore, searches out a process for purification not only economical and practical but also easy and simple to handle and becomes very urgent.
summary of the invention:
The present invention is directed to the refining technical deficiency of existing folic acid, a kind of purification process of medicinal folic acid is provided, it utilizes acid-base method to carry out purifying to folic acid crude product, and preparation that can be repeated meets the folic acid finished product of standards of pharmacopoeia; It is with low cost, easy and simple to handle, be easy to amplify; Purity and the production efficiency that can effectively improve on the other hand folic acid, be conducive to Application and Development in large-scale production.
The present invention realizes by the following technical solutions:
A purification process for medicinal folic acid, is characterized in that comprising the following steps:
(1) folic acid crude product is joined in purified water, be heated to 90～100 DEG C, add solid alkali in batches, regulate pH=11-13, treat that solid dissolves completely, add gac, be heated to seethe with excitement and keep micro-45 min that boil, filtered while hot; Mother liquor slowly drips acid solution while hot, regulates pH=2.5-3.5, cooling stirring and crystallizing, suction filtration, dry;
(2) sulphuric acid soln of 30-50% is slowly joined in the folic acid of above-mentioned primary purification, control temperature 45-60 DEG C, stir, until solid dissolves completely, stir half an hour; Slowly drip purified water, temperature control 55-75 DEG C, strengthens stirring dynamics, and solid is separated out, cooling, and suction filtration, a small amount of ethanol is washed, dry;
(3) above-mentioned secondary fine goods are joined in purified water, be heated to 90～100 DEG C, add solid alkali in batches, regulate pH=11-13, treat that solid dissolves completely, add gac, be heated to seethe with excitement and keep micro-45 min that boil, filtered while hot; Mother liquor slowly drips acid solution while hot, regulates pH=2.5-3.5, cooling stirring and crystallizing, and suction filtration, uses respectively sodium hydrogen carbonate solution, purified water and a small amount of washing with alcohol, forced air drying, yield is 68-75%.
Preferably, in step (1) and (3), described solid alkali is sodium hydroxide or potassium hydroxide, and described acid solution is hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid or the formic acid solution of 6-12M concentration; Preferred, described solid alkali is sodium hydroxide or potassium hydroxide, and described acid solution is the hydrochloric acid soln of 6M concentration.
Preferably, in step (2), described sulphuric acid soln concentration is 40%, 55 DEG C of acid adding control temperature, and adding water management temperature is 55-60 DEG C, stirring velocity 600-750 rev/min.
Further preferred, the purification process of described medicinal folic acid, comprises the following steps:
(1) folic acid crude product is joined in purified water, be heated to 90～100 DEG C, add solid sodium hydroxide in batches, regulate pH=12.0, treat that solid dissolves completely, add the gac of mass ratio 5%, be heated to seethe with excitement and keep micro-45 min that boil, filtered while hot; Mother liquor slowly drips the hydrochloric acid soln of 6M while hot, regulates pH=3.0, cooling stirring and crystallizing, and suction filtration is dry;
(2) 40% sulphuric acid soln is slowly joined in the folic acid of above-mentioned primary purification, control 55 DEG C of temperature, stir, until solid dissolves completely, stir half an hour; Slowly drip purified water, temperature control 55-60 DEG C, stirring velocity is 750 revs/min, solid is separated out, cooling, suction filtration, a small amount of ethanol is washed, dry;
(3) above-mentioned secondary fine goods are joined in purified water, be heated to 90～100 DEG C, add sodium hydroxide in batches, regulate pH=12.0, treat that solid dissolves completely, add the gac of mass ratio 5%, 45 min that are heated to seethe with excitement, filtered while hot; Mother liquor slowly drips 6M hydrochloric acid soln while hot, regulates pH=3.0, cooling stirring and crystallizing, and suction filtration, uses respectively sodium hydrogen carbonate solution, purified water and a small amount of washing with alcohol, forced air drying.
With respect to prior art, the invention has the beneficial effects as follows:
Major impurity in folic acid purge process and troublesome impurity are mainly pteroic acid.First the present invention uses alkali solution technique, the most of impurity in crude product and the higher impurity of content is removed, then foreign matter content is further reduced with acid pasting, and at this moment pteroic acid content can slightly increase, and finally re-uses alkali solution technique, and the content of pteroic acid is down to standards of pharmacopoeia.The systematic acid-base method that used of the present invention carries out purifying to folic acid crude product, and preparation that can be repeated meets the folic acid finished product of standards of pharmacopoeia, and its Folic Acid purity is more than 99%, and in the folic acid after refining, pteroic acid foreign matter content is below 0.1%.Present method is for the more difficult pteroic acid impurity of removing in folic acid crude product, with low cost, easy and simple to handle, be easy to amplify, yield is high; Purity and the production efficiency that can effectively improve folic acid, be conducive to Application and Development in large-scale production.
embodiment:
In order further to set forth technical scheme of the present invention, describe below in conjunction with embodiment.In the present embodiment, folic acid crude product is selected and is taked N-NSC 71042, trichloroacetone and TAHMS to come synthetic folic acid product, content >=90% of folic acid, pteroic acid content≤3.0% as intermediate.Should be noted that embodiment is to the further illustrating and explaining of summary of the invention, but not restriction to protection domain.
embodiment 1:
40% sulphuric acid soln, 470 ml are slowly joined to (pharmacopeia HPLC method detects, folic acid purity 91.1%, pteroic acid content 2.8%) in 50g folic acid crude product, control 55 DEG C of left and right of temperature, stir, until solid dissolves completely, stir half an hour.Slowly drip purified water 1.6L, temperature control≤60 DEG C, stirring velocity is 750 revs/min, solid is separated out, cooling, suction filtration, a small amount of ethanol is washed, dry.Highly finished product are joined in purified water, be heated to 90～100 DEG C, add sodium hydroxide 5.8g in batches, regulate pH=11.9 to treat that solid dissolves completely, add the gac of 2.5g, 45 min that are heated to seethe with excitement, filtered while hot.Mother liquor slowly drips 6M hydrochloric acid soln while hot, regulates pH=2.9, cooling stirring and crystallizing, and suction filtration, uses respectively sodium hydrogen carbonate solution, purified water and a small amount of washing with alcohol, forced air drying.Yield is that 86%, HPLC detects folic acid purity 98.2%, pteroic acid 1.1%.
embodiment 2:
Folic acid crude product 50g(pharmacopeia HPLC method is detected, folic acid purity 91.1%, pteroic acid content 2.8%) join in purified water 1.5L, be heated to 90～100 DEG C, add solid sodium hydroxide 8.3g in batches, regulate pH=11.8, treat that solid dissolves completely, add 2.5g gac, 45 min that are heated to seethe with excitement, filtered while hot.Mother liquor slowly drips while hot
concentrated hydrochloric acid solution, regulate pH=2.2, cooling stirring and crystallizing, suction filtration is dry.40% sulphuric acid soln 450ml is slowly joined in the folic acid of primary purification, control 55 DEG C of left and right of temperature, stir, until solid dissolves completely, stir half an hour.Slowly drip purified water 1.5L, temperature control≤60 DEG C, stirring velocity is 750 revs/min, solid is separated out, cooling, suction filtration, a small amount of ethanol is washed, dry.Secondary fine goods are joined in purified water, be heated to 90～100 DEG C, add sodium hydroxide 6.0g in batches, regulate pH=12.0, treat that solid dissolves completely, add the gac of 2.5g, 45 min that are heated to seethe with excitement, filtered while hot.Mother liquor slowly drips concentrated hydrochloric acid solution while hot, regulates pH=2.1, cooling stirring and crystallizing, and suction filtration, uses respectively sodium hydrogen carbonate solution, purified water and a small amount of washing with alcohol, forced air drying.Yield is that 61%, HPLC detects folic acid purity 98.9%, pteroic acid 0.3%.
embodiment 3:
Folic acid crude product 50g(pharmacopeia HPLC method is detected, folic acid purity 91.1%, pteroic acid content 2.8%) join in 1.5 L purified water, be heated to 90～100 DEG C, add solid sodium hydroxide 8.5 g in batches, regulate pH=12.1, treat that solid dissolves completely, add the gac of 2.5g, 45 min that are heated to seethe with excitement, filtered while hot.Mother liquor slowly drips the hydrochloric acid soln of 6M while hot, regulates pH=3.1, cooling stirring and crystallizing, and suction filtration is dry.Will
50% sulphuric acid soln440ml slowly joins in the folic acid of primary purification, controls 55 DEG C of left and right of temperature, stirs, until solid dissolves completely, stirs half an hour.Slowly drip purified water 1.5L, temperature control≤60 DEG C, stirring velocity is 750 revs/min, solid is separated out, cooling, suction filtration, a small amount of ethanol is washed, dry.Secondary fine goods are joined in purified water, be heated to 90～100 DEG C, add sodium hydroxide 5.8g in batches, regulate pH=12.2, treat that solid dissolves completely, add the gac of 2.5g, 45 min that are heated to seethe with excitement, filtered while hot.Mother liquor slowly drips 6M hydrochloric acid soln while hot, regulates pH=3.0, cooling stirring and crystallizing, and suction filtration, uses respectively sodium hydrogen carbonate solution, purified water and a small amount of washing with alcohol, forced air drying.Yield is that 72%, HPLC detects folic acid purity 99.0%, pteroic acid 0.3%.
embodiment 4:
Folic acid crude product 50g(pharmacopeia HPLC method is detected, folic acid purity 91.1%, pteroic acid content 2.8%) join in 1.5L purified water, be heated to 90～100 DEG C, add solid sodium hydroxide 8.4g in batches, regulate pH=12.0, treat that solid dissolves completely, add the gac of 2.6g, 45 min that are heated to seethe with excitement, filtered while hot.Mother liquor slowly drips the hydrochloric acid soln of 6M while hot, regulates pH=3.1, cooling stirring and crystallizing, and suction filtration is dry.Slow 40% sulphuric acid soln 460ml is joined in the folic acid of primary purification slowly, control 55 DEG C of left and right of temperature, stir, until solid dissolves completely, stir half an hour.Slowly drip purified water 1.5L,
temperature is 82-89 DEG C, stirring velocity is 750 revs/min, solid is separated out, and cooling, suction filtration, a small amount of ethanol is washed, dry.Secondary fine goods are joined in purified water, be heated to 90～100 DEG C, add sodium hydroxide 5.9g in batches, regulate pH=12.0, treat that solid dissolves completely, add the gac of 2.5g, 45 min that are heated to seethe with excitement, filtered while hot.Mother liquor slowly drips 6M hydrochloric acid soln while hot, regulates pH=3.0, cooling stirring and crystallizing, and suction filtration, uses respectively sodium hydrogen carbonate solution, purified water and a small amount of washing with alcohol, forced air drying.Yield is that 68%, HPLC detects folic acid purity 98.5%, pteroic acid 1.0%.
embodiment 5:
Folic acid crude product 50g(pharmacopeia HPLC method is detected, folic acid purity 91.1%, pteroic acid content 2.8%) join in 1.6L purified water, be heated to 90～100 DEG C, add solid sodium hydroxide 8.2g in batches, regulate pH=12.0, treat that solid dissolves completely, add the gac of 2.5g, 45 min that are heated to seethe with excitement, filtered while hot.Mother liquor slowly drips the hydrochloric acid soln of 6M while hot, regulates pH=3.1, cooling stirring and crystallizing, and suction filtration is dry.40% sulphuric acid soln 465ml is slowly joined in the folic acid of primary purification, control 55 DEG C of left and right of temperature, stir, until solid dissolves completely, stir half an hour.Slowly drip purified water 1.5L, temperature control≤60 DEG C, stirring velocity is 750 revs/min, solid is separated out, cooling, suction filtration, a small amount of ethanol is washed, dry.Secondary fine goods are joined in purified water, be heated to 90～100 DEG C, add sodium hydroxide 6.1g in batches, regulate pH=12.1, treat that solid dissolves completely, add the gac of 2.5g, 45 min that are heated to seethe with excitement, filtered while hot.Mother liquor slowly drips 6M hydrochloric acid soln while hot, regulates pH=3.1, cooling stirring and crystallizing, and suction filtration, uses respectively sodium hydrogen carbonate solution, purified water and a small amount of washing with alcohol, forced air drying.Yield is that 75%, HPLC detects folic acid purity 99.4%, pteroic acid 0.1%.
embodiment 6:
Folic acid crude product 50g(pharmacopeia HPLC method is detected, folic acid purity 91.1%, pteroic acid content 2.8%) join in 1.5L purified water, be heated to 90～100 DEG C, add solid sodium hydroxide 8.1g in batches, regulate pH=11.8, treat that solid dissolves completely, add the gac of 2.5g, 45 min that are heated to seethe with excitement, filtered while hot.Mother liquor slowly drips the hydrochloric acid soln of 6M while hot, regulates pH=3.2, cooling stirring and crystallizing, and suction filtration is dry.40% sulphuric acid soln 457ml is slowly joined in the folic acid of primary purification, control 55 DEG C of left and right of temperature, stir, until solid dissolves completely, stir half an hour.Slowly drip purified water 1.5L, temperature control≤60 DEG C, stirring velocity is 750 revs/min, solid is separated out, cooling, suction filtration, a small amount of ethanol is washed, dry.Secondary fine goods are joined in purified water, be heated to 90～100 DEG C, add sodium hydroxide 5.7g in batches, regulate pH=12.1, treat that solid dissolves completely, add the gac of 2.5g, 45 min that are heated to seethe with excitement, filtered while hot.Mother liquor slowly drips 6M hydrochloric acid soln while hot, regulates pH=2.9, cooling stirring and crystallizing, and suction filtration, uses respectively sodium hydrogen carbonate solution, purified water and a small amount of washing with alcohol, forced air drying.Yield is that 71%, HPLC detects folic acid purity 99.5%, pteroic acid 0.1%.
embodiment 7:
Folic acid crude product 50g(HPLC official method is detected, folic acid purity 88.7%, pteroic acid content 3.0%) join in 1.6L purified water, be heated to 90～100 DEG C, add solid sodium hydroxide 8.2g in batches, regulate pH=11.7, treat that solid dissolves completely, add the gac of 2.5g, 45 min that are heated to seethe with excitement, filtered while hot.Mother liquor slowly drips the hydrochloric acid soln of 6M while hot, regulates pH=3.1, cooling stirring and crystallizing, and suction filtration is dry.40% sulphuric acid soln 451ml is slowly joined in the folic acid of primary purification, control 55 DEG C of left and right of temperature, stir, until solid dissolves completely, stir half an hour.Slowly drip purified water, temperature control≤60 DEG C, stirring velocity is 750 revs/min, solid is separated out, cooling, suction filtration, a small amount of ethanol is washed, dry.Secondary fine goods are joined in purified water, be heated to 90～100 DEG C, add sodium hydroxide 5.5g in batches, regulate pH=12.2, treat that solid dissolves completely, add the gac of 2.6g, 45 min that are heated to seethe with excitement, filtered while hot.Mother liquor slowly drips 6M hydrochloric acid soln while hot, regulates pH=3.0, cooling stirring and crystallizing, and suction filtration, uses respectively sodium hydrogen carbonate solution, purified water and a small amount of washing with alcohol, forced air drying.Yield is that 68%, HPLC detects folic acid purity 99.3%, pteroic acid 0.1%.
The Purifying Process of Folic Acid simultaneous test that embodiment 1 is prior art.
Embodiment 2-3 is the preferred simultaneous test of Purifying Process of Folic Acid acid concentration of the present invention, and wherein embodiment 2 is for adopting the simultaneous test of concentrated hydrochloric acid, and embodiment 3 is for adopting the simultaneous test of 50% sulphuric acid soln.
Embodiment 4 is the preferred simultaneous test of Purifying Process of Folic Acid temperature of the present invention, and the sulphuric acid soln that embodiment 4 is 40% slowly joins in the folic acid of above-mentioned primary purification, controls 55 DEG C of left and right of temperature, stirs, until solid dissolves completely, stirs half an hour; Slowly drip purified water, temperature control 82-89 DEG C, strengthens stirring dynamics, and solid is separated out, cooling, and suction filtration, a small amount of ethanol is washed, dry.
Embodiment 5-7 is the test of the optimal procedure parameters of Purifying Process of Folic Acid of the present invention.
Can be found out by above-described embodiment 2-7, in the present invention, the processing step of optimization, processing parameter be the concentration, the temperature control effect while dripping of concentration, the sulfuric acid of hydrochloric acid especially, very large to the relationship between quality of folic acid final finished.And use method of the present invention can repeatability the qualified folic acid finished product of preparation pharmacopeia.
Claims (6)
1. a purification process for medicinal folic acid, is characterized in that comprising the following steps:
(1) folic acid crude product is joined in purified water, be heated to 90～100 DEG C, add solid alkali in batches, regulate pH=11-13, treat that solid dissolves completely, add gac, be heated to seethe with excitement and keep micro-45 min that boil, filtered while hot; Mother liquor slowly drips acid solution while hot, regulates pH=2.5-3.5, cooling stirring and crystallizing, suction filtration, dry;
(2) sulphuric acid soln of 30-50% is slowly joined in the folic acid of above-mentioned primary purification, control temperature 45-60 DEG C, stir, until solid dissolves completely, stir half an hour; Slowly drip purified water, temperature control 55-75 DEG C, strengthens stirring dynamics, and solid is separated out, cooling, and suction filtration, a small amount of ethanol is washed, dry;
(3) above-mentioned secondary fine goods are joined in purified water, be heated to 90～100 DEG C, add solid alkali in batches, regulate pH=11-13, treat that solid dissolves completely, add gac, be heated to seethe with excitement and keep micro-45 min that boil, filtered while hot; Mother liquor slowly drips acid solution while hot, regulates pH=2.5-3.5, cooling stirring and crystallizing, and suction filtration, uses respectively sodium hydrogen carbonate solution, purified water and a small amount of washing with alcohol, forced air drying.
2. the purification process of medicinal folic acid according to claim 1, is characterized in that: in step (1) and (3), adjust alkali pH=12, acid adjustment pH=3.0.
3. the purification process of medicinal folic acid according to claim 1, is characterized in that: in step (1) and (3), described solid alkali is sodium hydroxide or potassium hydroxide, and described acid solution is hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid or the formic acid solution of 6-12M concentration.
4. the purification process of medicinal folic acid according to claim 3, is characterized in that: in step (1) and (3), described solid alkali is sodium hydroxide, and described acid solution is the hydrochloric acid soln of 6M concentration.
5. the purification process of medicinal folic acid according to claim 1, is characterized in that: in step (2), described sulphuric acid soln concentration is 40%, 55 DEG C of acid adding control temperature, and adding water management temperature is 55-60 DEG C, stirring velocity 600-750 rev/min.
6. the purification process of medicinal folic acid according to claim 1, is characterized in that comprising the following steps:
(1) folic acid crude product is joined in purified water, be heated to 90～100 DEG C, add solid sodium hydroxide in batches, regulate pH=12.0, treat that solid dissolves completely, add the gac of mass ratio 5%, be heated to seethe with excitement and keep micro-45 min that boil, filtered while hot; Mother liquor slowly drips the hydrochloric acid soln of 6M while hot, regulates pH=3.0, cooling stirring and crystallizing, and suction filtration is dry;
(2) 40% sulphuric acid soln is slowly joined in the folic acid of above-mentioned primary purification, control 55 DEG C of temperature, stir, until solid dissolves completely, stir half an hour; Slowly drip purified water, temperature control 55-60 DEG C, stirring velocity is 750 revs/min, solid is separated out, cooling, suction filtration, a small amount of ethanol is washed, dry;
(3) above-mentioned secondary fine goods are joined in purified water, be heated to 90～100 DEG C, add sodium hydroxide in batches, regulate pH=12.0, treat that solid dissolves completely, add the gac of mass ratio 5%, 45 min that are heated to seethe with excitement, filtered while hot; Mother liquor slowly drips 6M hydrochloric acid soln while hot, regulates pH=3.0, cooling stirring and crystallizing, and suction filtration, uses respectively sodium hydrogen carbonate solution, purified water and a small amount of washing with alcohol, forced air drying.
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Cited By (8)
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| CN106749257A (en) * | 2017-01-19 | 2017-05-31 | 辛纪衡 | The purification process of folic acid |
| CN106946829A (en) * | 2017-05-27 | 2017-07-14 | 湖北华丹医药科技股份有限公司 | A kind of method that utilization raffinate produces nasmil bulk drug |
| CN107216353A (en) * | 2016-03-21 | 2017-09-29 | 山东诚创医药技术开发有限公司 | A kind of process for purification of Ceftaroline Fosamil imidazole salts |
| CN107602560A (en) * | 2017-08-15 | 2018-01-19 | 江西森泰药业有限公司 | The preparation technology of feed addictive folic acid |
| CN108948017A (en) * | 2017-05-23 | 2018-12-07 | 北京斯利安药业有限公司 | A kind of 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 |
| CN109761985A (en) * | 2019-01-28 | 2019-05-17 | 河北冀衡（集团）药业有限公司 | A method of purifying folic acid |
| CN115433189A (en) * | 2021-10-11 | 2022-12-06 | 苏州爱克森特医药科技有限公司 | Extraction process of high-purity folic acid for food and feed and folic acid |
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| CN107216353A (en) * | 2016-03-21 | 2017-09-29 | 山东诚创医药技术开发有限公司 | A kind of process for purification of Ceftaroline Fosamil imidazole salts |
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| CN108948017A (en) * | 2017-05-23 | 2018-12-07 | 北京斯利安药业有限公司 | A kind of purification process of folic acid |
| CN106946829A (en) * | 2017-05-27 | 2017-07-14 | 湖北华丹医药科技股份有限公司 | A kind of method that utilization raffinate produces nasmil bulk drug |
| 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 |
| CN107602560A (en) * | 2017-08-15 | 2018-01-19 | 江西森泰药业有限公司 | The preparation technology of feed addictive folic acid |
| CN109761985A (en) * | 2019-01-28 | 2019-05-17 | 河北冀衡（集团）药业有限公司 | A method of purifying folic acid |
| CN109761985B (en) * | 2019-01-28 | 2020-07-21 | 河北冀衡（集团）药业有限公司 | Method for purifying folic acid |
| CN115433189A (en) * | 2021-10-11 | 2022-12-06 | 苏州爱克森特医药科技有限公司 | Extraction process of high-purity folic acid for food and feed and folic acid |
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