CN108948017B - Purification method of folic acid - Google Patents
Purification method of folic acid Download PDFInfo
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Abstract
The invention belongs to the field of compound preparation, and discloses a method for purifying folic acid, wherein an acid treatment product obtained by acid refining of a folic acid crude product is subjected to alkali refining under the condition of pH 6-6.5, and a folic acid finished product is obtained by acid adjusting, crystallizing and drying. According to the method for purifying the folic acid, the pH value of alkali refining is controlled to be 6-6.5 after acid refining, so that the alkali refining step is carried out in a weak acid environment, the condition is mild, the possibility of producing the impurity A by hydrolyzing the folic acid is reduced, and the yield and the purity of the finished folic acid are improved. Experiments show that compared with the traditional folic acid purification method, the folic acid purification method effectively reduces the content of the impurity A, simultaneously reduces the content of the impurity D, and improves the yield and the purity of folic acid finished products.
Description
Technical Field
The invention belongs to the field of compound preparation, and particularly relates to a method for purifying folic acid, in particular to a method for purifying folic acid by reducing the content of folic acid impurity A (N- (4-aminobenzoyl) -L-glutamic acid).
Background
Folic acid is a basic variety of vitamin, is a substance essential for the growth and reproduction of body cells, and plays an important role in the division growth of cells and the synthesis of nucleic acid, amino acid and protein. The lack of folic acid in a human body can cause the abnormality of red blood cells, the increase of immature cells, anemia and the reduction of white blood cells; the lack of folic acid in pregnant women may cause low body weight, cleft lip and palate, heart defect, etc. in the fetus at birth.
There are many foods containing folic acid, but natural folic acid is extremely unstable, is easily oxidized by ultraviolet rays, high temperature and the like, and the bioavailability of folic acid is low, so that folic acid which can be really obtained from foods by a human body is not much. Human demand for folic acid depends on industrial synthesis of folic acid. The folic acid synthesized industrially can be kept stable within months or years, and is easy to absorb, and the human availability is about twice as high as that of the natural product. With the rapid development of the fields of medicine, food and the like, the demand of folic acid is rapidly increased, and the rapid development of folic acid synthesis technology is promoted.
However, the purity of the chemically synthesized folic acid crude product is not high, and further purification is needed to obtain a qualified folic acid finished product. At present, the folic acid is purified by a method combining acid refining and alkali refining. Firstly, carrying out an acid dissolution process, dissolving a crude product by using an acid solution, and carrying out elutriation and filter pressing on the dissolved crude product to obtain an acid extract; then carrying out an alkali dissolution process, adding water to the acid extract in an alkali dissolution reaction tank, stirring, adjusting the pH value to 9.0-9.5 at 90-100 ℃ by using an alkali solution, and carrying out filter pressing to obtain an alkali dissolution filtrate; and refining the alkali-soluble filtrate by acid regulation, crystallization, drying and the like to obtain a finished product. The folic acid purification method disclosed in the Chinese patent with the publication number of CN 102432610A comprises the following steps: dissolving the crude folic acid product with 25-35% dilute sulfuric acid, elutriating the dissolved crude folic acid product, and performing pressure filtration to obtain an acid extract; carrying out alkali dissolution on the acid extract by using alkali liquor, heating to 90-102 ℃, adjusting the pH value to 9.0-9.5 by using the alkali liquor, preserving the heat for 1 hour, adding activated carbon for decolorization, and carrying out filter pressing to obtain an alkali-dissolved filtrate; and then, salifying and refining the alkali liquor by using dilute acid to obtain a finished folic acid product. The method for purifying folic acid disclosed in the national patent publication No. CN 103102351B comprises: dissolving a folic acid crude product by using 15% -25% hydrochloric acid, adding water into the dissolved folic acid crude product solution, discharging, centrifuging, and directly drying by spin-drying to obtain an acid extract; in an alkali dissolution reaction vessel, mixing an acid extract with a solvent, adding an organic alkali solution to adjust the pH to 9.0-10.0, heating to 65-90 ℃, adding an adsorbent, keeping the temperature at 65-90 ℃ for 0.5-2 hours, carrying out filter pressing to obtain an alkali dissolution filtrate, adding the clarified alkali dissolution filtrate into a crystallization reaction vessel, heating to 80-90 ℃, adjusting the pH to 3.0-3.5 by using dilute hydrochloric acid, cooling to 55-60 ℃, and centrifuging to obtain a folic acid finished product.
The main impurities and the difficult-to-remove impurities in the folic acid purification process are impurity D (pteroic acid) and impurity A (N- (4-aminobenzoyl) -L-glutamic acid). The quality of the folic acid finished product in European pharmacopoeia requires that the content of impurity D is less than or equal to 0.6 percent, and the content of impurity A is less than or equal to 0.5 percent. The existing folic acid purification method mostly controls the content of an impurity D (pteroic acid) in folic acid to be less than or equal to 0.6 percent, and the content of an impurity A is still high.
Disclosure of Invention
In view of the above, the present invention aims to provide a method for purifying folic acid against the defects of the prior art. According to the purification method of folic acid, the alkali refining step is carried out in a mild weak acid environment, so that the possibility of folic acid hydrolysis is reduced, the content of impurity A is reduced, and the purity of folic acid finished products is improved.
In order to achieve the purpose of the invention, the invention adopts the following technical scheme.
A method for purifying folic acid comprises the steps of carrying out alkali refining on an acid treatment product obtained after acid refining of a folic acid crude product under the condition of pH 6-6.5, adjusting acid, crystallizing and drying to obtain a folic acid finished product.
According to the method for purifying the folic acid, the pH value of alkali refining is controlled to be 6-6.5 after acid refining, so that the alkali refining step is carried out in a weak acid environment, the condition is mild, the possibility of producing the impurity A by hydrolyzing the folic acid is reduced, and the yield and the purity of the finished folic acid are improved.
The acid refining is specifically to dissolve a folic acid crude product by using an acid solution, heating to 35-45 ℃ to dissolve until the folic acid crude product is clear, adding an adsorbent, stirring for 25-35 min, filtering, adding water into filtrate, stirring for 25-35 min, standing for 40-80 min, and filtering to obtain an acid treated product.
The acid solution in the step of acid refining may be at least one of sulfuric acid and hydrochloric acid.
The adsorbent in the step of acid refining may be activated carbon, diatomaceous earth or silica gel.
Further, the acid refining is preferably to add acid solution into the folic acid crude product, dropwise add the acid solution while stirring, heat up to 38-42 ℃ to dissolve until clarification, add the adsorbent, stir for 28-32min, filter, add water into the filtrate, stir for 28-32min, stand for 50-70min, filter to obtain an acid treated product; wherein the mass-volume ratio of the folic acid crude product to the acid solution is (2-4) to 4 in g/ml; the mass ratio of the adsorbent to the folic acid crude product is (0.5-1.5): 45; the mass volume ratio of the folic acid crude product to the water added into the filtrate (4-8) is 100 in g/ml.
Further, the volume ratio of the acid solution added to the crude folic acid in the acid refining step to the acid solution added dropwise with stirring is preferably 1: 1.
Further, the acid solution is preferably 45% -55% sulfuric acid or 20% -30% hydrochloric acid. In some embodiments the acid solution is 50% sulfuric acid; in other embodiments, the acid solution is 45% sulfuric acid; in other embodiments, the acid solution is 55% sulfuric acid; in other embodiments, the acid solution is 25% hydrochloric acid.
The purification method of folic acid of the invention is that after the folic acid crude product is refined by acid, alkali is refined. And the alkali refining is specifically to add water to the acid-treated product, stir, heat to 75-85 ℃, adjust the pH to 6.0-6.5 by using an alkali solution, add an adsorbent, stir for 25-35 min, and filter.
Wherein, the alkali solution in the alkali refining process can be at least one of sodium carbonate, sodium bicarbonate, ammonia water, sodium hydroxide and potassium hydroxide.
The adsorbent in the alkali refining process is preferably at least one of activated carbon, diatomite and silica gel.
Further, the alkali refining is preferably to add water into the acid treatment product, stir and heat the acid treatment product to 78-82 ℃, adjust the pH to 6.0-6.5 by using an alkali solution, add an adsorbent, stir for 28-32min, and filter the solution; wherein, the mass volume ratio of the acid treatment product to the water is (0.5-1.5) to 30 in g/ml; the mass ratio of the adsorbent to the acid-treated product is (0.5-1.5): 10.
Further, the alkali solution is preferably 5 to 15% sodium carbonate solution, 5 to 15% sodium bicarbonate solution, 5 to 15% ammonia water, 5 to 15% NaOH solution or 5 to 15% KOH solution.
In some embodiments the alkali solution is a 10% sodium carbonate solution. In some embodiments the base solution is a 10% aqueous ammonia solution. In some embodiments the base solution is a 10% sodium bicarbonate solution. In some embodiments the base solution is a 10% NaOH solution. In some embodiments the base solution is a 10% KOH solution.
Still further, the alkali solution is preferably a 10% sodium carbonate solution.
The purification method of folic acid collects filtrate after alkali refining, adjusts acid, crystallizes and dries to obtain folic acid finished products. The acid adjusting, crystallizing and drying are specifically to collect filtrate refined by alkali, heat the filtrate to 75-85 ℃, adjust the pH to 3.0-4.0 by using an acid solution, stir and cool the filtrate to 65-75 ℃, filter the filtrate after 25-35 min, and dry the filtrate.
Wherein, the acid solution in the steps of adjusting acid, crystallizing and drying is preferably at least one of sulfuric acid, hydrochloric acid and acetic acid.
Further, the acid adjusting crystallization and drying are preferably carried out by collecting the filtrate refined by alkali, adjusting the pH of the filtrate to 3.0-3.5 by using an acid solution at 78-82 ℃, stirring, cooling to 68-72 ℃, filtering after about 28-32min, and drying at 40-60 ℃.
Further, the acid solution in the acid adjusting crystallization and drying steps is preferably 3-8% dilute sulfuric acid, 7-15% hydrochloric acid or 30-40% acetic acid solution. In some embodiments the acid solution is 5% dilute sulfuric acid. In some embodiments the acid solution is 10% hydrochloric acid. In some embodiments the acid solution is a 35% acetic acid solution.
Further, the acid solution in the step of adjusting acid, crystallizing and drying is preferably 5% dilute sulfuric acid.
According to the technical scheme, the invention provides a folic acid purification method, acid-treated products of folic acid crude products after acid refining are subjected to alkali refining under the condition of pH 6-6.5, and folic acid finished products are obtained through acid adjusting, crystallization and drying. According to the method for purifying the folic acid, the pH value of alkali refining is controlled to be 6-6.5 after acid refining, so that the alkali refining step is carried out in a weak acid environment, the condition is mild, the possibility of producing the impurity A by hydrolyzing the folic acid is reduced, and the yield and the purity of the finished folic acid are improved. Experiments show that compared with the traditional folic acid purification method, the folic acid purification method effectively reduces the content of the impurity A, simultaneously reduces the content of the impurity D, and improves the yield and the purity of folic acid finished products.
Detailed Description
The invention discloses a method for purifying folic acid. Those skilled in the art can modify the process parameters appropriately to achieve the desired results with reference to the disclosure herein. It is expressly intended that all such similar substitutes and modifications which would be obvious to one skilled in the art are deemed to be included in the invention. While the methods and products of the present invention have been described in terms of preferred embodiments, it will be apparent to those of ordinary skill in the art that variations and modifications of the methods described herein, as well as other suitable variations and combinations, may be made to implement and use the techniques of the present invention without departing from the spirit and scope of the invention.
In order to further understand the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Unless otherwise specified, the reagents involved in the examples of the present invention are all commercially available products, and all of them are commercially available.
Example 1
Acid refining: adding 240mL of 50% sulfuric acid into 360g of folic acid crude product (detected by a pharmacopoeia HPLC method, the folic acid purity is 90.8%, the content of the impurity A is 3.2%, and the content of the impurity D is 2.6%), continuing to dropwise add about 240mL of 50% sulfuric acid under stirring, heating to 40 ℃ to dissolve until the solution is clear, adding 8g of active carbon, stirring for 30min, filtering, adding 6L of distilled water into the filtrate, stirring for 30min, standing for 1h, and filtering to obtain an acid-treated product.
Alkali refining: adding 7.2L distilled water into the acid treated product, stirring, heating to 80 deg.C, adjusting pH to 6.0 with 10% sodium carbonate solution, adding 25g active carbon, stirring for 30min, and filtering.
Acid adjusting and crystallizing: heating the filtrate to 80 deg.C, adjusting pH to 3.5 with 5% dilute sulfuric acid solution, stirring, cooling to 70 deg.C, filtering after about 30min, and oven drying at 50 deg.C to obtain folic acid product. The yield is 82%, the folic acid purity is 99.78% by HPLC, the impurity A is not detected, and the impurity D is 0.038%.
Example 2
Acid refining: adding 240mL of 45% sulfuric acid into 360g of folic acid crude product (detected by a pharmacopoeia HPLC method, the folic acid purity is 90.8%, the content of the impurity A is 3.2%, and the content of the impurity D is 2.6%), continuing to dropwise add 240mL of 45% sulfuric acid under stirring, heating to 40 ℃ to dissolve until the solution is clear, adding 8g of active carbon, stirring for 30min, filtering, adding 6L of distilled water into the filtrate, stirring for 30min, standing for 1h, and filtering to obtain an acid-treated product.
Alkali refining: adding 7.2L distilled water into the acid treated product, stirring, heating to 80 deg.C, adjusting pH to 6.5 with 10% ammonia water solution, adding 25g active carbon, stirring for 30min, and filtering.
Acid adjusting and crystallizing: heating the filtrate to 80 deg.C, adjusting pH to 3.5 with 5% dilute sulfuric acid solution, stirring, cooling to 70 deg.C, filtering after about 30min, and oven drying at 50 deg.C to obtain folic acid product. The yield is 83%, the folic acid purity is 99.80% by HPLC, the impurity A is not detected, and the impurity D is 0.029%.
Example 3
Acid refining: adding 240mL of 55% sulfuric acid into 360g of folic acid crude product (detected by a pharmacopoeia HPLC method, the folic acid purity is 90.8%, the content of the impurity A is 3.2%, and the content of the impurity D is 2.6%), stirring, continuously dropwise adding 240mL of 55% sulfuric acid, heating to 40 ℃, dissolving until the solution is clear, adding 8g of active carbon, stirring for 30min, filtering, adding 6L of distilled water into the filtrate, stirring for 30min, standing for 1h, and filtering to obtain an acid-treated product.
Alkali refining: adding 7.2L distilled water into the acid treated product, stirring, heating to 80 deg.C, adjusting pH to 6.5 with 10% sodium bicarbonate solution, adding 25g active carbon, stirring for 30min, and filtering.
Acid adjusting and crystallizing: heating the filtrate to 80 deg.C, adjusting pH to 3.5 with 5% dilute sulfuric acid solution, stirring, cooling to 70 deg.C, filtering after about 30min, and oven drying at 50 deg.C to obtain folic acid product. The yield is 85%, the folic acid purity is 99.71% by HPLC detection, the impurity A is 0.005%, and the impurity D is 0.042%.
Example 4
Acid refining: adding 240mL of 25% hydrochloric acid into 360g of folic acid crude product (detected by a pharmacopoeia HPLC method, the folic acid purity is 90.8%, the content of the impurity A is 3.2%, and the content of the impurity D is 2.6%), continuing to dropwise add 240mL of 25% hydrochloric acid under stirring, heating to 40 ℃ to dissolve until the solution is clear, adding 8g of diatomite, stirring for 30min, filtering, adding 6L of distilled water into the filtrate, stirring for 30min, standing for 1h, and filtering to obtain an acid-treated product.
Alkali refining: adding 7.2L distilled water into the acid treated product, stirring, heating to 80 deg.C, adjusting pH to 6.5 with 10% NaOH solution, adding 25g diatomaceous earth, stirring for 30min, and filtering.
Acid adjusting and crystallizing: heating the filtrate to 80 deg.C, adjusting pH to 3.5 with 10% hydrochloric acid solution, stirring, cooling to 70 deg.C, filtering after about 30min, and oven drying at 50 deg.C to obtain folic acid product. The yield is 81%, the folic acid purity is 99.68% by HPLC detection, the impurity A is 0.004%, and the impurity D is 0.045%.
Example 5
Acid refining: adding 240mL of 25% hydrochloric acid into 360g of folic acid crude product (detected by a pharmacopoeia HPLC method, the folic acid purity is 90.8%, the content of the impurity A is 3.2%, and the content of the impurity D is 2.6%), continuing to dropwise add 240mL of 25% hydrochloric acid under stirring, heating to 40 ℃ to dissolve until the solution is clear, adding 8g of silica gel, stirring for 30min, filtering, adding 6L of distilled water into the filtrate, stirring for 30min, standing for 1h, and filtering to obtain an acid-treated product.
Alkali refining: adding 7.2L distilled water into the acid treated product, stirring, heating to 80 deg.C, adjusting pH to 6.5 with 10% KOH solution, adding silica gel 25g, stirring for 30min, and filtering.
Acid adjusting and crystallizing: heating the filtrate to 80 deg.C, adjusting pH to 3.5 with 35% acetic acid solution, stirring, cooling to 70 deg.C, filtering after about 30min, and oven drying at 50 deg.C to obtain folic acid product. The yield is 83%, the folic acid purity is 99.73% by HPLC detection, the impurity A is 0.006%, and the impurity D is 0.051%.
Comparative example 1
Acid refining: dissolving 100g of crude folic acid (the folic acid purity is 90.8 percent, the impurity A content is 3.2 percent and the impurity D content is 2.6 percent by a pharmacopoeia HPLC method) by using 500ml of 18 percent hydrochloric acid, adding water into the obtained dissolved crude folic acid solution, discharging, centrifuging and drying to obtain the acid extract.
Alkali refining: adding 3000ml deionized water into the acid extract, adding ammonia water dropwise to adjust pH9, heating to 85 deg.C, re-measuring pH, and adding 20g activated carbon after pH is stable. Keeping the temperature at 85-90 ℃ for 1 hour, cooling to 55 ℃, and performing filter pressing.
Acid adjusting and crystallizing: the filtrate was heated to 80 ℃ and 10% hydrochloric acid was added dropwise to adjust the pH to 3.5. Heating to 83.5 deg.C, measuring pH at 3-3.5, and cooling to 57 deg.C. Discharging to a centrifugal machine for direct centrifugation, leaching twice with 300ml of deionized water with the temperature of 35-40 ℃, and drying at the temperature of 80 ℃ to obtain a refined folic acid product. Yield 80%, HPLC purity 99.4%, impurity a 0.31%, impurity D0.09%.
Comparative example 2
Acid refining: adding 240mL of 50% sulfuric acid into 360g of folic acid crude product (detected by a pharmacopoeia HPLC method, the folic acid purity is 90.8%, the content of the impurity A is 3.2%, and the content of the impurity D is 2.6%), continuing to dropwise add about 240mL of 50% sulfuric acid under stirring, heating to 40 ℃ to dissolve until the solution is clear, adding 8g of active carbon, stirring for 30min, filtering, adding 6L of distilled water into the filtrate, stirring for 30min, standing for 1h, and filtering to obtain an acid-treated product.
Alkali refining: adding 7.2L distilled water into the acid treated product, stirring, heating to 80 deg.C, adjusting pH to 9.5 with 10% NaOH solution, adding 25g active carbon, stirring for 30min, and filtering.
Acid adjusting and crystallizing: heating the filtrate to 80 deg.C, adjusting pH to 3.5 with 5% dilute sulfuric acid solution, stirring, cooling to 70 deg.C, filtering after about 30min, and oven drying at 50 deg.C to obtain folic acid product. The yield is 77%, the folic acid purity is 98.7% by HPLC detection, the impurity A is 0.41%, and the impurity D is 0.35%.
Comparative example 3
Acid refining: adding 360g of folic acid crude product (detected by a pharmacopoeia HPLC method, the folic acid purity is 90.8%, the impurity A content is 3.2%, and the impurity D content is 2.6%) into 240mL of 50% sulfuric acid, continuously dropwise adding about 240mL of 50% sulfuric acid under stirring, heating to 40 ℃ for clearing, adding 8g of active carbon, stirring for 30min, filtering, adding 6L of distilled water into the filtrate, stirring for 30min, standing for 1h, and filtering to obtain an acid-treated product.
Alkali refining: adding 7.2L distilled water into the acid treated product, stirring, heating to 80 deg.C, adjusting pH with 10% sodium carbonate solution 7, adding 25g active carbon, stirring for 30min, and filtering.
Acid adjusting and crystallizing: heating the filtrate to 80 deg.C, adjusting pH to 3.5 with 5% dilute sulfuric acid solution, stirring, cooling to 70 deg.C, filtering after about 30min, and oven drying at 50 deg.C to obtain folic acid product. The yield is 76%, the folic acid purity is 98.6% by HPLC detection, the impurity A is 0.39%, and the impurity D is 0.38%.
Comparative example 4
Acid refining: adding 360g of folic acid crude product (detected by a pharmacopoeia HPLC method, the folic acid purity is 90.8%, the impurity A content is 3.2%, and the impurity D content is 2.6%) into 240mL of 50% sulfuric acid, continuously dropwise adding about 240mL of 50% sulfuric acid under stirring, heating to 40 ℃ for clearing, adding 8g of active carbon, stirring for 30min, filtering, adding 6L of distilled water into the filtrate, stirring for 30min, standing for 1h, and filtering to obtain an acid-treated product.
Alkali refining: adding 7.2L distilled water into the acid treated product, stirring, heating to 80 deg.C, adjusting pH with 10% sodium carbonate solution 5, adding 25g active carbon, stirring for 30min, and filtering.
Acid adjusting and crystallizing: adjusting pH to 3.5 with 5% dilute sulphuric acid solution at 80 deg.C, stirring, cooling to 70 deg.C, filtering for about 30min, and oven drying at 50 deg.C to obtain folic acid product. The yield is 78%, the folic acid purity is 98.3% by HPLC detection, the impurity A is 0.38%, and the impurity D is 0.40%.
In conclusion, compared with the traditional folic acid purification methods (comparative examples 1-4), the folic acid purification method (examples 1-5) provided by the invention effectively reduces the content of the impurity A and the impurity D, and improves the yield and the purity of the finished folic acid.
Claims (12)
1. A method for purifying folic acid is characterized in that an acid treatment product obtained by acid refining of a folic acid crude product is subjected to alkali refining under the condition of pH 6-6.5, acid adjustment crystallization is performed, and a folic acid finished product is obtained through drying;
the acid refining is specifically to dissolve a folic acid crude product by using an acid solution, heating to 35-45 ℃ to dissolve until the folic acid crude product is clear, adding an adsorbent, stirring for 25-35 min, filtering, adding water into filtrate, stirring for 25-35 min, standing for 40-80 min, and filtering to obtain an acid treated product;
the alkali refining is specifically that the acid treatment product is added with water and stirred, the temperature is raised to 75-85 ℃, the pH value is adjusted to 6.0-6.5 by using an alkali solution, an adsorbent is added, the stirring is carried out for 25-35 min, and the filtration is carried out;
the acid adjusting, crystallizing and drying are specifically to collect filtrate refined by alkali, heat the filtrate to 75-85 ℃, adjust the pH to 3.0-4.0 by using an acid solution, stir and cool the filtrate to 65-75 ℃, filter the filtrate after 25-35 min, and dry the filtrate.
2. The purification method according to claim 1, wherein the acid solution in the acid refining step is at least one of sulfuric acid and hydrochloric acid; the adsorbent is at least one of active carbon, diatomite and silica gel.
3. The purification method according to claim 1, wherein the acid refining is specifically to add an acid solution to the folic acid crude product, dropwise add the acid solution while stirring, heat up to 38-42 ℃ to dissolve until clarification, add an adsorbent, stir for 28-32min, filter, add water to the filtrate, stir for 28-32min, stand for 50-70min, filter to obtain an acid-treated product; wherein the mass-volume ratio of the folic acid crude product to the acid solution is (2-4) to 4 in g/ml; the mass ratio of the adsorbent to the folic acid crude product is (0.5-1.5): 45; the mass volume ratio of the folic acid crude product to the water added into the filtrate (4-8) is 100 in g/ml.
4. The purification process according to claim 3, wherein the acid solution is 45-55% sulfuric acid or 20-30% hydrochloric acid.
5. The purification method according to claim 3, wherein the acid solution is 45% sulfuric acid, 50% sulfuric acid, 55% sulfuric acid, or 25% hydrochloric acid.
6. The purification method according to claim 1, wherein the alkali solution is at least one of sodium carbonate, sodium bicarbonate, ammonia water, sodium hydroxide, and potassium hydroxide; the adsorbent is at least one of active carbon, diatomite and silica gel.
7. The purification method according to claim 1, wherein the alkali refining is specifically that water is added to the acid-treated product, the temperature is raised to 78-82 ℃ by stirring, the pH is adjusted to 6.0-6.5 by an alkali solution, an adsorbent is added, the mixture is stirred for 28-32min, and the filtration is carried out; wherein, the mass volume ratio of the acid treatment product to the water is (0.5-1.5) to 30 in g/ml; the mass ratio of the adsorbent to the acid treatment product is (0.5-1.5) to 10; the alkali solution is 5-15% sodium carbonate solution, 5-15% sodium bicarbonate solution, 5-15% ammonia water, 5-15% NaOH solution or 5-15% KOH solution.
8. The purification process according to claim 7, wherein the alkali solution is a 10% sodium carbonate solution, a 10% sodium bicarbonate solution, 10% ammonia, a 10% NaOH solution or a 10% KOH solution.
9. The purification method according to claim 1, wherein the acid solution in the steps of acid adjusting crystallization and drying is at least one of sulfuric acid, hydrochloric acid and acetic acid.
10. The purification method according to claim 1, wherein the acid adjusting crystallization and drying are specifically implemented by collecting the filtrate refined by alkali, adjusting the pH of the filtrate to 3.0-3.5 by using an acid solution at 78-82 ℃, stirring and cooling to 68-72 ℃, filtering after 28-32min, and drying at 40-60 ℃.
11. The purification process according to claim 10, wherein the acid solution is 3-8% dilute sulfuric acid, 7-15% hydrochloric acid or 30-40% acetic acid solution.
12. The purification method according to claim 10, wherein the acid solution is a 5% dilute sulfuric acid, 10% hydrochloric acid, or 35% acetic acid solution.
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| 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 |
| 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 |
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