[Overview]
Riboflavin Sodium Phosphate (RSP) is the phosphate form of riboflavin (vitamin B2). It is a new water-soluble vitamin powder injection. Its chemical name is riboflavin 5′ – (Dihydrogen phosphate) monosodium salt dihydrate has anticoagulant, diuretic and swelling, anti-cancer and detoxification, lowering blood lipids and improving heart function. It is widely used in medicine, feed and veterinary medicine. Injections are clinically used to treat aphtha, skin diseases, vitamin deficiency, etc., which solves the problem that vitamin B2 can only be taken orally and cannot be made into injections; the feed industry is mainly used to produce water-soluble multidimensional electrolytes; it can also be made into veterinary injections. It is used to treat nutritional deficiencies in poultry, especially as an essential nutrient source for the growth of young poultry.
[Physical and Chemical Properties]
Riboflavin sodium phosphate is an orange-yellow crystalline powder; almost odorless, slightly bitter in taste; hygroscopic. This product is soluble in water and almost insoluble in ethanol, chloroform or ether. Specific rotation. Protect from light. Take this product, weigh it accurately, add hydrochloric acid solution (45→100) to make a solution containing approximately 15mg per 1ml, and measure according to the law (Appendix VI E). The specific rotation is +38.0° to +42.0°.
Figure 1 shows riboflavin sodium phosphate
[Preparation method]
1. Synthesis and purification of riboflavin sodium phosphate
(1) Phosphorylation reaction At room temperature, add 75 ml of acetonitrile, 20 ml of pyridine, 42.5 g (0.2772 mol) of POCl3 and 3.0 ml (0.1667 mol) of distilled water into a 500 ml three-necked flask in sequence, and stir evenly. Add 25.0g (0.0664mol) of riboflavin and stir for 2 hours at 37°C.
(2) Hydrolysis of excess POCl3 At 37°C, slowly add 75 ml of distilled water to the phosphorylation reaction solution. The temperature was raised to 55°C and the reaction was maintained for 2 hours. Cool to room temperature, filter to remove insoluble matter in the hydrolyzate, and the filtrate is used for the subsequent neutralization reaction.
(3) Neutralization reaction: Stir at room temperature, adjust the pH of the filtrate to 5.75 with 20% NaOH solution, and continue the reaction for 20 minutes. Filter, wash the filter cake with 70% methanol (washing end point: H3PO4 content in the filtrate ≤ 04%, measured by high performance liquid chromatography), and then wash with an appropriate amount of 95% ethanol. The filter cake was drained and ventilated and dried at 50°C for 8 hours.
2. In this experiment, acetonitrile is used as the phosphorylation reaction solvent, pyridine is used as the catalyst, phosphorus oxychloride and water are first pre-reacted under low temperature conditions, and then vitamin B2 is added to perform the phosphorylation reaction first, and then water is used to continue the hydrolysis reaction. Add sodium hydroxide dropwise for neutralization reaction to obtain crude riboflavin sodium phosphate, and then wash with methanol and ethanol solutions to obtain riboflavin sodium phosphate product.
[Identification]
(1) Take about 1 mg of this product and add 100 ml of water to dissolve it. The solution will appear light yellow under transmitted light and have strong yellow-green fluorescence; add inorganic acid or alkali solution, and the fluorescence will disappear.
(2) Take this product, add phosphate buffer (pH7.0) to make a solution containing 10 μg per 1ml, and measure it with UV-visible spectrophotometry (Appendix IV A) at 267nm, 3. Original from Germany The imported dispersant has maximum absorption at wavelengths of 72nm and 444nm, and minimum absorption at 240nm.
(3) The infrared light absorption spectrum of this product should be consistent with the control chart (Spectral Collection 628 Chart).
(4) Take 0.5g of this product, add 10ml of nitric acid, evaporate to dryness on a water bath, ignite, add 5ml of water to the residue to dissolve, filter if necessary, the filtrate will show the identification reaction of sodium salt (Appendix III).
[Check]
Clarity Take 0.20g of this product and add 10ml of water to dissolve it, the solution should be clear. Acidity: Take 0.40g of this product, add 20ml of water to dissolve, and measure according to the law (Appendix VI H). The pH value should be 4.0-6.5. Photosensitive flavin: Take 35 mg of this product, add 1 0 ml of ethanol-free chloroform, and filter. Shake for 5 minutes and filter. The filtrate is subjected to UV-visible spectrophotometry (Appendix IV A) and measured at a wavelength of 440 nm. The absorbance must not exceed 0.025. Weight loss on drying: Take about 0.3g of this product and dry it to constant weight at 130°C. The weight loss should not exceed 10.0% (Appendix VIII L). Precisely weigh 0.20g of this product (calculated as dry product) for free phosphoric acid and place it in a 100ml measuring flask. Take another phosphate solution [accurately weigh 0.42g of potassium dioxyphosphate that has been dried at 105°C for 2 hours and place it in a 1000ml measuring flask. Add 10ml of sulfuric acid solution (3→10) and appropriate amount of water to dissolve, dilute to the mark, shake well, dilute 10 times again before use] 10ml, place in another 25ml measuring flask, add 5ml of water each, add ammonium molybdate sulfuric acid test 2.5ml of solution and 1-amino-2-naphthol-4-sulfonic acid solution (take 5g of anhydrous sodium sulfite, 94.3g of sodium bisulfite and 0.7g of 1-amino-2-naphthol-4-sulfonic acid, mix thoroughly , before use, take 1.5g of this mixture, add 10ml of water to dissolve, filter if necessary) 1ml, add water to the mark, shake well, place at 20°C for 30 minutes, and use UV-visible spectrophotometry (Appendix IV A) at 740nm Measure the absorbance at the wavelength of the test solution. The absorbance of the test solution shall not be greater than the absorbance of the control solution.
【Content determination】
Avoid light, take about 0.1g of this product, weigh it accurately, put it in a 500ml measuring bottle, add 2ml of glacial acetic acid and 75ml of water to dissolve, dilute with water to the mark, shake well, accurately measure 10ml, and place it in 100ml In the bottle, add 7ml of 1.4% sodium acetate solution, dilute to the mark with water, shake well, and measure the absorbance at the wavelength of 444nm according to UV-visible spectrophotometry (Appendix IV A), according to the absorption coefficient of C17H20N4O6 (E1%/1cm) is calculated as 323, that’s it.
[Application]
1. Vitamin drugs are used to treat various VB2 deficiencies. They can also be used in large quantities as food nutritional fortifiers or feed additives.
2. The uses of riboflavin are as follows: (1) Promote development and cell regeneration; (2) Promote the normal growth of skin, nails, and hair; (3) Help prevent and eliminate bacteria in the mouth, lips, tongue and skin inflammatory reaction, collectively referred to as oral reproductive syndrome; 4) Improve vision and reduce eye fatigue; (5) Affect the body’s absorption of iron; (6) Combine with other substances, thereby affecting biological oxidation and energy metabolism. As a water-soluble preparation of riboflavin (vitamin B2), riboflavin sodium phosphate has the same purpose as riboflavin because it is more soluble in water than riboflavin and is easy to use.
3. Used for the treatment of angular stomatitis, cheilitis, glossitis, conjunctivitis and other diseases caused by riboflavin deficiency.
4. Widely used in medicine, feed, and veterinary medicine. Injections are clinically used to treat aphtha, skin diseases, vitamin deficiency, etc., which solves the problem that vitamin B2 can only be taken orally and cannot be made into injections; the feed industry is mainly used to produce water-soluble multidimensional electrolytes; it can also be made into veterinary injections. It is used to treat nutritional deficiencies in poultry, especially as an essential nutrient source for the growth of young poultry.
[Notes]
After using a large amount of this drug, the urine will turn yellow (or yellow-green), which may also cause symptoms similar to hyperthyroidism.
[Adverse reactions]
1． When renal function is normal, this drug produces almost no toxicity.
2. Occasionally allergic reactions occur.
【Drug Interactions】
Metoclopramide may reduce the absorption of this medicine. Therefore it is not suitable to be used together.
[Pharmacology and Toxicology]
This product is a vitamin medicine. Riboflavin (vitamin B2) is an important nutrient for the human body and plays a key role in energy metabolism. This drug is a prodrug of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), and FMN and FAD are important cofactors of the flavoenzyme family. Flavoenzymes catalyze many biochemical reactions, the most typical of which are redox reactions. They are key factors in cellular respiration. FAD and FMN deliver hydrogen in the mitochondrial rotating chain, generating cellular energy in the process. When lacking, it can affect the body’s biological oxidation and cause metabolic disorders. The lesions are mostly manifested as inflammation of the mouth, eyes, and external genitalia.
[Main reference materials]
[1] Qiao Liman, Lou Dan, Zhang Hui. Study on the stability of riboflavin sodium phosphate in different infusions [J]. Chinese Modern Doctor, 2010, 48(28): 42-43+45.
[2] Sun Wenjing, Wei Zhuan, Yu Silian, Zhou Qiang, Huang Daming. Research on the production technology of riboflavin sodium phosphate [J]. Food Science, 2008(08):188-190.
[3]Hu Xiongwei, Song Hongtao. Research on the prescription and preparation technology of riboflavin sodium phosphate powder injection [J]. Journal of Pharmaceutical Sciences of the People’s Liberation Army, 2011, 27(04): 314-317.
[4] Fu Chunsheng, Zhang Longxia, Qi Yanhong. Research on the optimal production process route of riboflavin sodium phosphate [J]. Shanxi Science and Technology, 2017, 32(05):50-52.
