Preparation and application of 5-riboflavin phosphate sodium salt dihydrate_Industrial additives

Background and overview^[1]

5-Riboflavin phosphate sodium salt dihydrate is the hydrate of riboflavin sodium phosphate.

Riboflavin, also known as VB2, its chemical name is 6,7-dimethyl-10-(1′-D-ribitol)-isoalloxazine, which is necessary to maintain normal metabolism of the body. A water-soluble vitamin, it is an important prosthetic group of many enzyme systems in the body – flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN). It is involved in the energy production of the body. Metabolism and substance metabolism. If the body lacks riboflavin, it will affect the normal oxidation in the body, cause material metabolism disorders, cause the body to develop a series of diseases, and in severe cases may lead to death of the body. In view of riboflavin’s extensive and important physiological functions, the World Health Organization lists it as one of the six major indicators for evaluating human growth, development and nutritional status.

Riboflavin sodium phosphate (riboflavin5′-phosphate sodium) is the NaOH neutralization product of FMN (riboflavin 5′-phosphate, riboflavin5′-phosphate). It is one of the important derivatives of riboflavin. 1. Its physiological effects are basically the same as those of Albemarle riboflavin from the United States. It is mainly used as a drug, food nutrition fortifier or feed additive to treat various VB2 deficiencies. Many studies have shown that riboflavin and its derivatives also have diuretic, anti-cancer, lowering blood lipids and improving heart function. Compared with riboflavin, the solubility of riboflavin sodium phosphate in water is greatly increased, and it is easily absorbed and utilized by the body. Clinically, it can be made into compound VB2 preparations, eye drops and injections with stable concentration, etc., which is more convenient to use. The scope of application is wider.

Preparation of riboflavin sodium phosphate^[1]

Add 20ml water, 250ml tetrahydrofuran and 48g riboflavin into a 1000ml three-neck flask, stir and dissolve into a mixture, cool to 5~10℃, slowly add 100ml sodium metaphosphate aqueous solution (20.4g Japan Mitsubishi sodium metaphosphate is dissolved in 100ml of water), control the temperature at 28~30℃, after the addition is completed, raise the temperature to 40℃, react for 2~3 hours, stop the reaction, cool to 15~25℃, pour the reaction solution into a large beaker, add 250ml of water, and stir At the same time, pay attention to cooling down and removing insoluble matter. Add 10% sodium hydroxide solution to the filtrate, adjust the pH value to 9, stir at room temperature for 0.5 hours, and filter with suction. Use hydrochloric acid to adjust the pH of the mother liquor to 5 to 6. Filter with suction to obtain a white solid, which is washed with a small amount of 50% ethanol. The product was then dissolved in 95% ethanol, filtered, crystallized and dried to obtain 59.2 g of orange solid, with a yield of 92%. At the same time, high performance liquid chromatography was used to analyze and its purity was 98.5%.

Apply^[2]

CN201880028493.6 reports a compound emulsion for parenteral application. The emulsion of the present invention contains 3.24-3.96 mg, preferably 3.4-3.8 mg, more preferably 3.6 mg of vitamin B2 in a single container. Different forms of vitamin B2 are available. For example, vitamin B2 may be used in the form of riboflavin, riboflavin phosphate, riboflavin sodium phosphate, riboflavin sodium phosphate dihydrate, flavin mononucleotide or other vitamin B2 derivatives. The compound emulsion of the present invention is stable and easy to handle, transport and administer.