CN103435651A - Synthesis method and process of riboflavin sodium phosphate - Google Patents
Synthesis method and process of riboflavin sodium phosphate Download PDFInfo
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- CN103435651A CN103435651A CN2013104108627A CN201310410862A CN103435651A CN 103435651 A CN103435651 A CN 103435651A CN 2013104108627 A CN2013104108627 A CN 2013104108627A CN 201310410862 A CN201310410862 A CN 201310410862A CN 103435651 A CN103435651 A CN 103435651A
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- riboflavin
- sodium phosphate
- riboflavin sodium
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Abstract
The invention relates to a production method of a medical product and particularly relates to a synthesis process of riboflavin sodium phosphate, belonging to the technical field of medicinal chemistry. The process comprises the following steps: subjecting riboflavin and phosphoryl chloride to esterification reaction under a certain condition to generate riboflavin phosphate ester, filtering, removing solid materials, and hydrolyzing the filtrate to obtain a crude product of the riboflavin sodium phosphate; filtering the crude product of the riboflavin sodium phosphate, collecting filter cakes, and crystallizing the filter cakes to obtain a riboflavin sodium phosphate crystal; and filtering the riboflavin sodium phosphate crystal, and adding the filter cakes into a dryer for drying to obtain the product. The method is easy to obtain raw materials, low in cost, simple in reaction, easy to control, high in yield and capable of realizing mass production in workshops. The production method has wide application prospects on the aspect of a synthesis process of riboflavin sodium phosphate.
Description
Technical field
The present invention relates to a kind of production pharmaceutical product, be specifically related to a kind of synthesis technique of riboflavin sodium phosphate, belong to the pharmaceutical chemistry technical field.
Background technology
Riboflavin sodium phosphate is a kind of anti-inflammatory type medicine, the treatment of the diseases such as the bridou that is applicable to be caused by riboflavin deficiency, cheilitis, glossitis, film inflammation and scrotitis.Also can be used for the control of cardiovascular disorder, hypoferric anemia, esophagus System Malignant Tumor, also can be in a large number as food enrichment.At present, the chemical synthesis route of riboflavin sodium phosphate can be divided into two kinds: the production technique of riboflavin 5'-sodium phosphate all adopts chemical synthesis process both at home and abroad, its synthetic route mainly contains two: the one, in organic solvent, use the phosphorus oxychloride (POCL of riboflavin and partial hydrolysis
3) reaction generation FMN, then be hydrolyzed excessive POCl
3, in the neutralization of the sodium hydroxide with excessive, obtain after filtration riboflavin 5'-sodium phosphate (FMN); The 2nd, use riboflavin and POCl in organic solvent
3reaction product nucleus flavine 4, the 5-cyclic phosphorochloridate, then be hydrolyzed phosphinylidyne thing and excessive POCl
3.What at present, the explained hereafter of China's riboflavin 5-sodium phosphate adopted is article one synthetic route.The production of riboflavin sodium phosphate adopts chemical synthesis usually, in organic solvent, makes riboflavin and phosphorus oxychloride (POCl
3) reaction generates FMN, then with the neutralization of NaOH solution, more after filtration, washing, drying and other steps obtain finished product.It is very simple that this technique seems, but only have 5 '-FMN to have physiologically active in the phosphorylation reaction product due to riboflavin, and it is more difficult optionally carrying out this reaction.In addition, using the high yield of the phosphorylation agent realization response of trying one's best few is also to be also one of gordian technique of this technique.Therefore, what the design selected is article one synthetic route, and it is advanced, optimizes.Be divided into reaction, hydrolysis, three processes of crystallization in this production, single batch of output is larger, in reaction, has solid materials to produce, the available semicontinuous mode of production.
Summary of the invention
The objective of the invention is to synthesize a kind of medicinal product riboflavin sodium phosphate by technology simply and easily.
The synthesis technique of riboflavin sodium phosphate involved in the present invention, the present invention is by raw material through a series of esterification, and hydrolysis reaction obtains thick product riboflavin sodium phosphate, then through crystallization reaction and refining dry, obtain the finished product, pure riboflavin sodium phosphate powder.
The present invention is a kind of synthesis technique of riboflavin sodium phosphate, it is characterized in that: this synthesis technique comprises the steps:
Esterification: in the reactor at acetonitrile as solvent, add pyridine as catalyzer, esterification product nucleus flavin phosphate and some other impurity can occur in riboflavin and phosphorus oxychloride, as 6,7-dimethylisoalloxazine.Filter, remove solid materials, filtrate is got to hydrolysis kettle and carry out next step reaction.
Hydrolysis reaction: in hydrolysis kettle, add acidifying, then add the sodium hydroxide neutralization, obtain the riboflavin sodium phosphate crude product.Filter, collect filter cake, filter cake is added in crystallization kettle and carries out purifying.
Crystallization reaction: in crystallizer, add the salt acid for adjusting pH in 5.5 left and right, now carry out crystallization, obtain the riboflavin phosphate sodium crystal, filter.
Refining: as filter cake to be carried out in moisture eliminator to drying, obtain product after drying.
Advantage of the present invention and effect are:
Present method raw material is easy to get, and cost is low, and reaction is simple, is easy to control, and yield is high, and can be used for the workshop production in enormous quantities.
The accompanying drawing explanation
For above and other purpose of the present invention, feature, advantage and embodiment more can be become apparent, the description of the drawings is as follows:
Fig. 1 illustrates a kind of preparation flow figure according to an embodiment of the present invention.
Embodiment
The present invention is further described by the following embodiment.
Embodiment:
1, acetonitrile, pyridine, phosphorus oxychloride, riboflavin are added to reactor, then add water (1h), under 15 ℃, keep 16h.
2, filter, with metal bar millipore filter filter 23 h, filtrate is beaten to hydrolytic decomposition pot.
3, hydrolysis adds hydrochloric acid (9%) acidifying in hydrolytic decomposition pot, after reaction 6h, adds sodium hydroxide (25%) that pH is transferred to 9 left and right, and is cooled to 40 ℃ under 50 ℃, reaction 12h.
4, filter, with metal bar millipore filter filter 23 h, filter cake is thrown to crystallizer.
5, crystallization adds hydrochloric acid (30%) to neutralize excessive sodium hydroxide in crystallizer, and pH is transferred to 5.5, lets cool to 5 ℃.Keep 10h.
6, filter, filter 1.5 hours with whizzer, wet cake is added to the making beating tank, with the making beating of ethanol water, stir one hour, refilter 1.5h.
7. dry, use the dry 12h of double cone dryer under 50 ℃, until in product, moisture is less than 10%.
Claims (4)
1. the synthesis technique of a riboflavin sodium phosphate, it is characterized in that: this synthesis technique comprises the steps:
(1) esterification: in the reactor at acetonitrile as solvent, add pyridine as catalyzer, esterification product nucleus flavin phosphate and some other impurity can occur in riboflavin and phosphorus oxychloride, as 6,7-dimethylisoalloxazine.Filter, remove solid materials, filtrate is got to hydrolysis kettle and carry out next step reaction.
(2) hydrolysis reaction: in hydrolysis kettle, add acidifying, then add the sodium hydroxide neutralization, obtain the riboflavin sodium phosphate crude product.Filter, collect filter cake, filter cake is added in crystallization kettle and carries out purifying.
(3) crystallization reaction: in crystallizer, add the salt acid for adjusting pH in 5.5 left and right, now carry out crystallization, obtain the riboflavin phosphate sodium crystal, filter.
(4) refining: as filter cake to be carried out in moisture eliminator to drying, obtain product after drying.
2. the synthesis technique of riboflavin sodium phosphate according to claim 1, it is characterized in that: the temperature of described esterification is 15 ℃.
3. the synthesis technique of riboflavin sodium phosphate according to claim 1, is characterized in that: acidifying 6h in described hydrolysis reaction, the rear reaction of neutralization 12 hours.
4. the synthesis technique of riboflavin sodium phosphate according to claim 1, it is characterized in that: described crystallization reaction carries out under 5 ℃.
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| CN2013104108627A CN103435651A (en) | 2013-09-11 | 2013-09-11 | Synthesis method and process of riboflavin sodium phosphate |
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| CN2013104108627A CN103435651A (en) | 2013-09-11 | 2013-09-11 | Synthesis method and process of riboflavin sodium phosphate |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106674225A (en) * | 2016-11-09 | 2017-05-17 | 珠海同源药业有限公司 | Riboflavin sodium phosphate compound and pharmaceutical composition thereof |
| CN107286194A (en) * | 2017-06-07 | 2017-10-24 | 山西集翔生物工程有限公司 | A kind of riboflavin phosphate process for producing sodium |
| CN108530479A (en) * | 2018-05-17 | 2018-09-14 | 扬州工业职业技术学院 | A kind of new synthetic method of calcium glycerophosphate synthetic intermediate glycerophosphate |
| WO2020056714A1 (en) * | 2018-09-21 | 2020-03-26 | 邦泰生物工程(深圳)有限公司 | Method for preparing high-purity riboflavin sodium phosphate |
-
2013
- 2013-09-11 CN CN2013104108627A patent/CN103435651A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106674225A (en) * | 2016-11-09 | 2017-05-17 | 珠海同源药业有限公司 | Riboflavin sodium phosphate compound and pharmaceutical composition thereof |
| CN107286194A (en) * | 2017-06-07 | 2017-10-24 | 山西集翔生物工程有限公司 | A kind of riboflavin phosphate process for producing sodium |
| CN108530479A (en) * | 2018-05-17 | 2018-09-14 | 扬州工业职业技术学院 | A kind of new synthetic method of calcium glycerophosphate synthetic intermediate glycerophosphate |
| CN108530479B (en) * | 2018-05-17 | 2020-03-31 | 扬州工业职业技术学院 | Novel method for synthesizing intermediate glycerophosphate from calcium glycerophosphate |
| WO2020056714A1 (en) * | 2018-09-21 | 2020-03-26 | 邦泰生物工程(深圳)有限公司 | Method for preparing high-purity riboflavin sodium phosphate |
| CN111094309A (en) * | 2018-09-21 | 2020-05-01 | 邦泰生物工程(深圳)有限公司 | Preparation method of high-purity riboflavin sodium phosphate |
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Application publication date: 20131211 |
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| WD01 | Invention patent application deemed withdrawn after publication |