From Big Medical Encyclopedia

RIBOFLAVINUM (synonym: vitamin B 2 , lactoflavin, vitamin G, ovoflavin, lyuminoflavin, uroflavin, gepatoflavin) — 7,8-Dimetil-10-N-(I' - D - ribitil) - izoalloksazin, C 17 H 20 O 6 N 4 , water-soluble vitamin of a complex B.


Biol. R.'s role is defined by its participation in creation of flavin coenzymes (see) — a flavinmononukleotida (FMN,-fos-veil Riboflavinum-5) and the flavinadenindinukleotid (FAD) which are a part of the catalytic centers of the major oxidation-reduction enzymes so-called flavin oxidoreductases (see), or yellow enzymes (see). These enzymes (see) take part in oxidation fatty acids (see), oxidizing decarboxylation pyruvic acid (see) and alpha and keto-glutaric to - you (see. Keto-glutaric acid ), in a cycle tricarboxylic to - t (see. Tricarboxylic acids cycle ), in oxidizing phosphorylation (see). Thus flavin enzymes occupy one of the central places in processes of energy balance. FAD-zavisimye enzymes participate also in synthesis of coenzymatical forms of rat anti-acrodynia factor (pyridoxal phosphate) and Folacinum (tetrahydrofolic to - you). Besides, R. is a part of rhodopsin, protecting a retina from harmful effects of Uv-radiation. In medicine drugs P. are used as pharmaceuticals.

R.'s lack causes pathology of various systems of an organism. So ariboflavinosis (see) an eye, a nervous sitema, etc. is characterized by damage of skin, mucous membrane of a mouth. The expressed R.'s insufficiency (see. Vitamin deficiency ) causes profound functional and structural changes in bark of adrenal glands, disturbance of processes of a hemogenesis, exchange of iron, and also glyconeogenesis. At R.'s insufficiency process of transformation is broken phenylalanine (see) in catecholamines (see). R.'s hypovitaminosis reflects adversely on a condition of natural immunity. At insufficiency in R.'s organism note decrease in light and color sensitivity of a retina of eyes. R.'s deficit in an organism of the pregnant woman, especially in critical periods of differentiation of fabrics and an organogenesis of a fruit, can have teratogenic effect.

In R.'s nature meets in three forms: free R. and its coenzymatical forms — FMN and FAD. Formation of coenzymatical forms P. in an organism happens to participation of ATP and two enzymes — flavokinaza (KF catalyzing synthesis of FMN, and the flavinnukleotidfosforilaza catalyzing synthesis of FAD from FMN and ATP: Riboflavinum + ATP -> Riboflavinum-5 '-phosphate (FMN) + ADF and FMN + ATP —> FAD + a pyrophosphate. In the sum these three connections make so-called general R. U of the person and animals free R. contains in a pigmented layer of a retina of an eye, in milk and urine. At sufficient security to R. its concentration is equal in whole blood of the person to 40 — 50 mkg / 100 ml, in erythrocytes 15 — 20mkg/100 ml, in leukocytes of 200 — 250 mkg / 100 ml, in a blood plasma of 2 — 3 mkg / 100 ml.

In 1933. Kuna with sotr. from ovalbumin allocated R., received it in a crystal look and established chemical structure of this connection. In 1935 Riboflavinum was synthesized in R. Kong and Karrer's laboratories (R. by Karrer).

Pier. weight (weight) of Riboflavinum 376,4. Riboflavinum represents crystals of yellow-orange color, bitter taste, inodorous, t°pl 280 — 290 ° (with decomposition). Riboflavinum crystallizes from water solutions of pyridine, ethanol and from the diluted solutions acetic to - you. R.'s solubility in water is low — from 0,013 to 0,23%, in ethanol — 0,0045%. In chloroform, benzene, ether, acetone P. it is not dissolved. In acid medium R.'s solubility increases; pH of saturated water solution of Riboflavinum 6,0, at this size pH is it isoelectric point (see). The absorption spectrum of R. (in water) has maxima at 445, 374, 268, 223 nanometers with molar coefficient of absorption (in cm - 1 * m - 1 ) 12,3*10 3  ; 10,8*10 3  ; 31,4*10 3  ; 30,1*10 3 respectively.

The range of fluorescence of R. is in a flavovirent spectral range (515 — 615 nanometers) with a maximum at 565 nanometers (in water). The greatest intensity of fluorescence of R. is observed at pH 6,0 — 8,0. The maximum of a range of initiation of fluorescence of R. is at 450 nanometers, a maximum of a radiation spectrum — at 530 nanometers. In neutral and acid solutions P. optically it is inactive, in alkaline solutions finds optical activity, intensity a cut depends on R.'s concentration, and rotates the plane of the polarized light to the left. The river has amphoteric properties, termostabilen, but is extremely sensitive to effect of light. On light P. in alkaline solution turns in lyumiflavin (7,8,10-trimetilizoalloksazin, biologically inactive connection possessing fluorescence soluble in chloroform), and in acid and neutral solutions — into a lumichrom (7,8-dimetilizoalloksazin). Hydrosulphite and zinc in acid medium and other reducers easily recover R. in colourless, not fluorescent dihydroriboflavinum, or leykoflavin. Oxygen of air leykoflavin quickly is oxidized in R. Riboflavin it is capable to accept one electron with education of the free radical of seven-quinone (see. Radicals free , Quinones ).

By substitution of methyl groups in a molecule P. in situation 7 and 8 other alkyls or chlorine, and also replacements of a D-ribose with other sugars or changes of an izoalloksazinovy cycle are received structural analogs — antagonists of River. Anti-vitamin properties of analogs of R. are specific in relation to different types of microorganisms, animals and the person. The most expressed antiriboflavinovy action in a human body shows galaktoflavin-7,8-dimetil-10-N-(1' - D - dultsitil) - izoalloksazin.

The ruble arriving with food is soaked up in a small bowel where partially turns into FNM and FAD under the influence of a flavokinaza and FAD-pirofosforilaza (KF Generally formation of coenzymatical forms P. happens in a liver and kidneys. In blood P. and its coenzymatical forms communicate proteins of plasma, preferential albumine, and are transported in various bodies. At proteinaceous and caloric insufficiency disturbances of absorption of R., its phosphorylation in a mucous membrane of intestines, and also disturbance of its transport because of the low content of albumine in a blood plasma therefore R.'s removal with urine significantly amplifies are observed. The person and animals do not synthesize R., as well as others vitamins (see), unlike plants, a number of bacteria, pleseny and yeast. Comes to a human body of R. only with food. R.'s synthesis by microflora of a large intestine matters only at nek-ry animal species.

Daily need of the adult for R. is equal 1,9 — 3,0 mg, about 0,7 mg on 1000 kcal of a diet. Signs of insufficiency of R. arise at consumption less than 0,25 mg of vitamin on 1000 kcal a day. The need for R. increases at pregnant women and the feeding women, at various diseases and stressful states. The norm of consumption of R. for various categories of the population is established taking into account age, sex, intensity and the nature of work.

The liver, kidneys, heart, milk and dairy products, eggs, green vegetables are especially rich with R. (see the tab.). The main sources of R. in food of the person are milk and dairy products, to-rye provide a half of daily need of the person for this vitamin. With bakery products from the flour enriched with vitamins, the person receives apprx. 10% of daily quantity of the River. At thermal treatment of foodstuff of loss are essential. However under the influence of light of loss of R. much more. If at pasteurization of milk only 5% R. which is contained in it collapse, then two-hour impact of a sunlight leads more than 50% of Riboflavinum to loss.

For determination of content of R. in biol. material use a microbiological or flyuorimetrichesky method. The microbiological method is based on measurement of growth of test culture of Lactobacillus casei ATCG 7469 depending on R.'s maintenance in culture medium. The method is sensitive, but is very labor-consuming. The Flyuorimetrichesky method is much simpler. Use of a method of determination of content of R. by its direct measurement fluorescence (see) more preferably at the estimated high content of Riboflavinum (see. Bertsch — Bessey — Lauri a method ). R.'s definition in urine is carried out usually by Maslenikova's method — Gvozdova, offered in 1956, at Krom foreign fluorescent substances in urine are exposed to preliminary oxidation. The method of definition of lyumiflavinovy fluorescence is applied preferential at the estimated low maintenance of R. in the studied material. The photolysis of flavins in alkaline condition to the lyumiflavin which is easily extracted by chloroform and fluorescing with a big photon yield is the cornerstone of this method.

Riboflavinum as drug

as remedies in medical practice are used: Riboflavinum (Riboflavinum; synonym of Beflavin, etc., GFH), riboflavinmononukleotid (Riboflavinum mo nonucleotidum; synonym: Riboflavinfosfat, Flavinmononukleotid, Coflavinasi, etc.) and Flavinatum (Flavinatum; synonym: Flavinadenindinukleotid, FAD, etc.), to-rye treat group vitamin drugs (see). Flavinatum has the most expressed specific activity, the Ruble is least active.

Drugs P. are used for prevention and treatment hypo - and an ariboflavinosis; in the conditions of the increased need of an organism for vitamins (at hard physical work, steady psychological stress, pregnancy, feeding of newborns), and also at prolonged use of antibiotics or sulfanamide drugs, at a hemeralopia, conjunctivitis, irites, a keratitis, helcomas, a cataract, at it is long not healing wounds and ulcers, at dysfunctions of intestines, to a spr, a viral hepatitis, a radial illness, and also at the general disturbances of food, adynamy. Riboflavinmononukleotid and Flavinatum contributing to normalization of a metabolism in a cardiac muscle apply at the heart diseases which are followed by a myocardial dystrophy. Flavinatum is applied in complex therapy abiotrofichesky (especially central tapetoretinalny) and dystrophic processes of a retina of an eye, at the hereditary hemolitic anemias caused by a carriage of unstable hemoglobin, and also connected with genetically caused deficit of a glyukozo-6-phosphate-dehydrogenase (KF at a porphyria, psoriasis, seborrhea, pink and youthful eels, streptodermas (an angular stomatitis, a cheilitis), at hron. diseases of a liver, pancreas and intestines.

Rubles appoint inside after food. Riboflavinmononukleotid and Flavinatum enter intramusculary, subcutaneously or use in the form of eye drops.

The single medical dose of R. at intake for adults makes 0,005 — 0,01 g (5 — 10 mg); in hard cases of R. accept 0,01 g 3 times a day within 1 — 1,5 month. To children appoint 0,002 — 0,005 g (to 0,01 g) in day depending on age. It must be kept in mind that treatment by excessively high doses of R. can lead to creation of considerable concentration of R. in an organism, in this case because of bad solubility of R. it is capable to cause obstruction of renal tubules.

A medical dose of a riboflavinmononukleotid for adult 0,01 g (1 ml of 1% of solution) once a day. The course of treatment consists of daily injections within 10 — 20 days. To children enter the same dose daily within 3 — 5 days, and then 2 — 3 times a week; in total appoint 15 — 20 injections to a course. At diseases of eyes enter intramusculary on 0,2 — 0,5 ml 1% of solution of a riboflavinmononukleotid within 10 — 15 days and at the same time dig in in eyes 1% solution on 0,1 — 0,5 ml within 8 — 15 days daily.

Flavinatum is entered intramusculary slowly, and at a disease of eyes — under a conjunctiva of an eyeglobe at the same time into both eyes on 0,0006 g (0,3 ml of 0,2% of solution) every other day; on a course of treatment of 10 —-15 injections. Courses are repeated in 8 — 12 months.

At a porphyria Flavinatum is applied intramusculary on 0,002 g by 3 times a day within 1 month. 2 — 3 repeated courses in a year at constant appointment in River are recommended. At skin diseases, hron. diseases of a liver, pancreas and intestines Flavinatum is appointed the adult on 0,002 g of 1 — 2 time a day; at cirrhoses of a liver to 0,01 g a day daily or every other day; to children on 0,001 — 0,002 g a day. The course of treatment proceeds from 5 to 40 days depending on therapeutic effect of drug. If necessary courses are repeated in half a year.

As the proofreader of side effects at prolonged use of antibiotics or streptocides Flavinatum is entered on 0,001 — 0,002 g once a day, daily during all course of treatment antibiotics or streptocides.

At introduction of Flavinatum under a conjunctiva of an eyeglobe emergence of dizziness, headache, dacryagogue is possible. In these cases it is necessary to pass to intramuscular introduction.

Forms of release: Riboflavinum — powder, a dragee and tablets on 0,002 g; tablets on 0,005 and on 0,01 g; riboflavinmononukleotid — 1% solution in ampoules on 1 ml; Flavinatum — in the form of the lyophilized powder on 0,002 g in ampoules. Just before introduction prepare 0,2% solution (contents of an ampoule are dissolved in 1 ml of isotonic solution of sodium chloride).

Store in the place protected from light.

Table. CONTENT of RIBOFLAVINUM (&vnbsp; &mgnbsp; on 100 g of a product) In SOME FOODSTUFF (according to M. F. Nesterina and I. M. Skurikhina, 1979)

Bibliography: Vitamins, under the editorship of M. I. Smirnov, page 214, M., 1974; Clinical pharmacology, under the editorship of V. V. Za-kusov, page 353, M., 1978; Mashkov - with to and y M. D. Pharmaceuticals, p.1, page 482, M., 1978; Experimental vitaminology, under the editorship of Yu. M. Ostrovsky, page 224, Minsk, 1979; Yakovlev T. N. Treatment-and-prophylactic vitaminology, page 26, L., 1981; F about at N. a. M b and at and V. Riboflavin, Progr. Food Nutr. Sci., v. 2, p. 357, 1977, bibliogr.; Riboflavin, ed. by R. S. Rivlin, N. Y. — L., 1975; The vitamins, ed. by W. H. Sebrell a. R. S. Harris, v. 5, p. 1, N. Y. — L., 1972, bibliogr.

H. G. Bogdanov; V. M. Avakumov (pharm.).