The method of obtaining riboflavin
(57) Abstract:The invention relates to the production of Riboflavin (vitamin B2). To simplify the technological process, reducing time and increasing the yield of the target product condensation azeribajan with barbituric acid in the medium aliphatic alcohol in the presence of acetic acid at the boiling temperature of the mixture is carried out in the presence of additives water, taken in a mass ratio of barbituric acid: water 1: (0,6 - 1,2). As the aliphatic alcohol is preferable to use alcohols having an acidity equal to or higher than the acidity of isopropanol. It allows to conduct the process in a homogeneous phase, to exclude from the process using the absolute solvents, to intensify the process of condensation and to improve the yield of the target product by reducing decomposition and resinification of azeribajan and Riboflavin. 1 C.p. f-crystals, 1 table. The invention relates to an improved method of obtaining Riboflavin (vitamin B2), which finds application as medicines and nutritional supplements.Known  a method of producing Riboflavin by condensation of azeribajan with barb is islote boiling, output technical Riboflavin 70%
The disadvantage of this method is the low yield of the target product, as in the purification and recrystallization of the product is lost on average 8% to 10% of Riboflavin.A known method of producing Riboflavin by condensation of 3,4-xylyl-6-phenyl-azo-D-arbitraria (azeribajan) with barbituric acid in an anhydrous environment in a mixture of lower aliphatic alcohols C2-C5and aromatic hydrocarbon o-xylene and/or toluene) in the presence of a catalytically acting acetic acid with continuous distillation of the formed water azeotrope  Output technical Riboflavin 84 - 86,1%
The disadvantage of this method is the difficulty of obtaining Riboflavin pharmacopoeial quality and the use of two solvents.Known  the method of obtaining Riboflavin with a sufficiently high yield of the target product pharmacopoeial quality (71,5 74,2%), which is chosen as a prototype. Target product, according to atoi method, obtained by condensation of azeribajan with barbituric acid in absolute aliphatic alcohol (butanol) in the presence of acetic acid at the boiling temperature of the mixture with continuous azeotropic the kind in acidic medium, precipitation with water, washing and drying of the target product.Used in the way the prototype of the absolute solvent is not possible to conduct the reaction in a homogeneous environment, as barbituric acid in alcohols and esters of acetic acid is not soluble. Reaction mass is heterogeneous, which leads to local overheating, and, consequently, to decrease the yield of the target product.The disadvantage of this method is the complexity of the technological process consisting of a preliminary dehydration of aliphatic alcohols and carrying out the condensation in a heterogeneous environment, the duration of the technological process and not a high yield of the target product.The purpose of the invention increase the yield of the target product, simplifying the process and reducing its duration.This is achieved by condensation of azeribajan with barbituric acid in the medium aliphatic alcohol by boiling the addition of water, taken in a mass ratio of barbituric acid: water 1: (0,6oC1,2), then cooled and the release of a technical product, the processing of hydrogen peroxide in an acidic medium by precipitation with water, washing and slotosch, equal acidity isopropanol or higher.Distinctive features of the proposed method are additive in the reaction mixture of water mass ratio of barbituric acid: water 1: (0,6 1,2). The use of water allows the process in homogeneous phase, because barbituric acid soluble in hot water  and azeribajni in hot alcohols  While heating the reaction mass in an aqueous-alcoholic medium azeribajni and barbituric acid into solution, which creates favorable conditions of flow of the reaction and increases the speed of its passing.Experimental work has shown that when the ratio of barbituric acid: water 1: more than 1.2, the decrease of the output (example 4), as excess water reduces the reaction rate, which can be explained, firstly, by reducing the solubility of azeribajan, and, secondly, by shifting the equilibrium of the reaction to the left, as water is one of the products of the condensation reaction.When carrying out the condensation at a ratio of barbituric acid: water below the lower limit or in absolute solvent also observed a decrease in the output (examples 5, 7, 9, 11 and 14), due to the decreased solubility barbecue alcohols or mixtures thereof, moreover, it is preferable to use aliphatic alcohols with high acid numbers (equal to or more than acidity isopropanol).The acidity of these alcohols catalyzes the reaction of condensation as used organic acids. Known  the relative scale of acidity of alcohols:
Tertiary butanol 1100
In a series of solvents ethanol-n-butanol-isopropanol-tertiary butanol yield of Riboflavin under other equal conditions as with additives and without additives water increases, and it was confirmed by experimental data (examples of 13.8, 1,15 and 14.9).It should be noted that carrying out the condensation of azeribajan with barbituric acid by adding water at the beginning of the condensation process is not so obvious and simple, although the solubility of barbituric acid in hot water has long been known. The fact that the second source reactant azeribajni not soluble in water and up to the present time, it was thought that the presence of water in the condensation process of azeribajan with barbituric acid is not desirable  which explains the COI is us relations provides solubility barbituric acid, do not reduce the solubility of azeribajan and does not shift the equilibrium of the reaction to the left.The presence at the beginning of the condensation process additives water and use as a medium of aliphatic alcohols with high acidity allows to increase the yield of the target product to 83 86,6% due to homogenization of the environment and intensification of the process of condensation, which in turn leads to a reduction in the degree of decomposition of the sugar components of azeribajan.Increase the yield of the target product is also achieved by improving the solubility of Riboflavin in acidic aqueous-alcoholic medium at the time of its formation, which provides a uniform supply of heat, prevents local overheating and loss of initial reagents with the decomposition products and resinification.The reaction mass after completion of the condensation process is uniform and transportable, which eliminates clogging of pipes and fittings and associated loss of the target product.In addition, the use of water additives allows to simplify the technological process, as this eliminates the need to use absolute solvents and prior alkoxy is STI. It is new, because applicants are not aware of any sources that provide data on the use of additives water by condensation of azeribajan with barbituric acid.It has an inventive step, since it is not clear from the prior art, since in the literature there are no data about the positive influence of addition of water on the reaction of condensation of azeribajan with barbituric acid.The invention is industrially applicable, because its implementation does not require any special equipment or inaccessible and expensive raw materials.The method is illustrated by the following examples, the main results of which are shown in the pivot table.In the examples 1, 2, 3, 6, 8, 10, 12, 13 and 15 presents the results obtained according to the invention in the claimed range. The deviation from the set parameters of the condensation process (examples 4, 5, 7, 9, 11 and 14) reduces the yield of the target product. Example 16 in terms of the prototype using absolute aliphatic alcohol with continuous distillation of the water azeotrope. The yield of the target product is significantly lower in comparison with the invention.
Yah, with the content of the basic substance, respectively 97,5% 98,0%
Example 1. A mixture of 10 g (0,028 mol) of azeribajan, 4.7g (being 0.036 mol) of barbituric acid and 13.3 ml of acetic acid, 70 ml of 95% isopropanol (ratio of barbituric acid: water 1 0,6) is heated with stirring in a sealed reactor at 105 110oC for 4 h under a pressure of 1 MPa At the end of the reaction mass is then cooled to 20oC and filtered. Technical vitamin on the filter is washed with 20 ml of isopropanol, then with hot water until a light yellow wash water.
The medical Riboflavin 8,63 g (82.5 per cent).Example 7 (comparative). Was carried out analogously to example 1, as the aliphatic alcohol used absolute mixture of isopropanol and n-amyl alcohol (2 1).The medical Riboflavin of 7.96 g (76,1%).Example 8. Was carried out analogously to example 1, as the aliphatic alcohol used 95% n-butanol. The ratio of barbituric acid water 1 0,6.The medical Riboflavin of 8.37 g (80,0%).Example 9 (comparative). Was carried out analogously to example 1, as the aliphatic alcohol used absolute n-butanol.The output of medical vitamin 7,66 g (73.2 per cent).Example 10. Was carried out analogously to example 1, as the aliphatic alcohol used was a mixture of the ptx2">Example 11 (comparative). Was carried out analogously to example 1, as the aliphatic alcohol used absolute mixture of n-butanol and isoamyl alcohol (1 1). The medical Riboflavin 7.6 g (72.6 per cent).Example 12. Was carried out analogously to example 1,as the aliphatic alcohol used a mixture of amyl alcohols with a water content of 5%
The medical Riboflavin of 7.96 g (76,1%).Example 13. Was carried out analogously to example 1, as the aliphatic alcohol used 95% ethanol.The medical Riboflavin 7,56 g (72,3%).Example 14 (comparative). Was carried out analogously to example 1, as the aliphatic alcohol used absolute ethanol.The output of medical vitamin 7,11 g (68%).Example 15. Was carried out analogously to example 1, as the aliphatic alcohol used 95% tertiary butanol. The ratio of barbituric acid water 1 0,6.The medical Riboflavin 9,06 g (86.6 per cent).Example 16 (the prototype). A mixture of 10 g (0,028 mol) of azeribajan, 4.7g (being 0.036 mol) of barbituric acid and 13.3 ml of acetic acid and 70 ml of absolute n-butanol is heated under stirring to a boil, formed during Rea is concani reaction mass is then cooled and filtered. Further processing is as in example 1.The medical Riboflavin 7,74 g (74,0%).Literature
1. USSR author's certificate N 93306 class. C 07 D 57/32, 18.01.80.2. Patent Czechoslovakia N 156800 class. C 07 C 51/50, 184.108.40.206. Chemical and pharmaceutical journal. M. 1986, N 1, c. 102 105.4. Chemical encyclopedia, M. 1988, vol 1, S. 240.5. Shneidman L. O. Production of vitamins. M. 1973, S. 121.6. Kraskov A. P. Acid-base titration in nonaqueous solutions. M. 1967, S. 57.7. Patent Czechoslovakia N 131622 class. C 07 C 51/50, 15.03.69 (prototype). A method of producing Riboflavin by condensation of 3,4-xylyl-6 - phenylazo-D-arbitraria with barbituric acid in the medium aliphatic alcohol in the presence of acetic acid at the boiling temperature of the mixture, then cooling the reaction mass and the selection of a technical product, process hydrogen peroxide in an acidic environment, sedimentation of water, rinsing, and drying of the target product, wherein the condensation is carried out in the presence of additives water, taken in a mass ratio of barbituric acid water 1 0,6 1,2.2. The method according to p. 1, characterized in that aliphatic alcohol use aliphatic alcohols with acid
< / BR>The inventive compound is a derivative of the heterocyclic system thiazolo/5,4-in/indole type a:
< / BR>Derivatives of this system, for example, 2,4-dimethylthiazole /5,4-in/indole (In), described as intermediate products for the synthesis of polymethine dyes used as photosensitizers [1 4] however, in the literature there is no information about the biological activity of the system (a) and its derivatives
where X is-CH=CH -, or S;
R1lower alkyl or trifluoromethyl;
R2chlorine or fluorine;
R3the radical of the formula R4-(CH2)nC or R5-O-CH2-C_C-, where n is the integer 0, 1 or 2;
R4phenyl or mono-, di-, or tricyclic 5-7-membered heterocyclic radical containing as heteroatoms 0 or S, and/or 1-3 nitrogen atom, unsubstituted or substituted lower alkoxy, oxo, actigraphy or chlorine,
R5phenyl or pyridylethyl provided that when n is 0, the radical R4must be attached through a carbon to carbon link, and that R5attached via a carbon to oxygen connection with RAG-antagonistic properties
< / BR>in which Z is hydrogen, halogen or lower alkyl;
R1is lower alkyl, cycloalkyl or aryl; and
R2is lower alkyl or cycloalkyl;
which are used to mitigate various dysfunctions of memory, which are characterized by a cholinergic deficit such as disease Alzheimer and as analgesic agents
FIELD: organic chemistry, biochemistry, biology.
SUBSTANCE: invention relates to a pharmaceutical composition eliciting the inhibitory effect on activity of serine protease (caspase-3) in the form of tablet, capsule or injections placed into acceptable package, to a method for its preparing and a method for treatment of diseases associated with enhanced activation of apoptosis. The composition comprises compound 2,3-dihydro-1H-benzo[g]pteridine-4-one of the general formula (1) (1)
or its salt with pharmacologically acceptable acid as an active component taken in pharmaceutically effective amount wherein X means oxygen (O) or sulfur (S) atom; R1 and R2 represent independently of one another hydrogen atom, inert substitute taken among the group including low- or non-reactive and optionally substituted radical, such as (C1-C7)-alkyl, (C2-C7)-alkenyl, (C2-C7)-alkynyl, (C1-C7)-alkoxy-group, (C7-C12)-aralkyl, (C7-C12)-heterocyclylalkyl, (C7-C12)-alkaryl, (C3-C10)-cycloalkyl, (C3-C10)-cycloalkenyl, phenyl, aryl, heterocyclyl; optionally substituted hydroxy-(C1-C5)-alkyl group; R3, R4, R5 and R6 represent independently of one another hydrogen, halogen atom, -CF3, -CN, inert substitute taking among the group including low- or non-reactive and optionally substituted radical, optionally substituted hydroxyl group, optionally substituted hydroxy-(C1-C5)-alkyl group, optionally substituted amino-group, optionally substituted amino-(C1-C7)-alkyl group, optionally substituted carboxy-(C1-C7)-alkyl group, optionally substituted (C1-C6)-alkylcarboxy-(C1-C6)-alkyl group, optionally substituted carbamoyl group, optionally substituted (C1-C6)-alkylcarbamoyl group, optionally substituted sulfamoyl group. Also, invention relates to applying compounds of the formula (1) for preparing pharmaceutical composition and experimental study (in vitro and in vivo) processes associated with apoptosis.
EFFECT: improved preparing method, valuable medicinal and biochemical properties of composition.
7 cl, 1 dwg, 2 tbl, 5 ex
FIELD: veterinary science.
SUBSTANCE: about 20-25 d before calving one should introduce intramuscularly 0.5%-sodium selenite solution for cows at the dosage of 10 ml. Twice before and twice after calving at 10-d-long interval - tetravit at the dosage of 10 ml at the content of 50000 IU vitamin A, 25000 IU vitamin D, 20 mg vitamin E and 5 mg vitamin F per 1 ml. Succinic acid should be introduced 20-25 d both before and after calving at the dosage of 1.0 g. The method provides efficient correction of the main values of homeostasis in cows after calving.
EFFECT: higher efficiency of normalization.
2 ex, 4 tbl
FIELD: veterinary science.
SUBSTANCE: one should introduce endovit complex preparation once daily for dogs. Moreover, during the first 5 d endovit should be introduced at the dosage of 30 mg/kg, during the next 10 d - 25 mg/kg and during the last 5 d 20 mg/kg body weight. The suggested innovation provides normalization of myocardial trophic nature, interrupts dystrophic processes in it, improves functional state of cardiac conductory system and, thus, provides the chance to treat both the main and secondary disease by the mentioned scheme without applying any additional cardiological remedies.
EFFECT: higher efficiency of therapy.
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to the development of medicines used for enhancing resistance of humans and animals to hypothermia. Agent for enhancing resistance of humans and animals to hypothermia comprises nicotinic acid, glutamic acid, riboflavin, ascorbic acid, uniquinone, succinic acid, polyethylene oxide and water taken in the definite ratio. Also, invention proposes a method for enhancing resistance of humans and animals to hypothermia involving administration of the abovementioned agent 30 min before works associated with hypothermia and after its termination for activation of vital essential biochemical processes. Invention provides enhancing resistance to overcooling under extreme conditions and using in surgery practice in cooling organs (in operations in heart and brain).
EFFECT: enhanced effectiveness and valuable medicinal properties of agent.
2 cl, 2 tbl, 1 dwg, 2 ex
FIELD: medicine, in particular veterinary.
SUBSTANCE: invention relates to method for treatment of cattle intoxicated with Cynoglossum officinalis containing in feed hey as admixture. Claimed method includes administration perorally of sorbent, namely healthy feed supplement containing in dose of aluminum silicate in dose of 0.15 g/kg of body mass; saccharose in dose of 0.5-1.0 g/kg of body mass; and beta-carotene comprising 10-20 mg/ml of active ingredient in dose of 2 ml 1 time per day; administration intramuscularly of 1 % riboflavin mononucleotide solution 3 ml; 1 % pyridoxine hydrochloride solution 1 time per day; tetravit in dose of 3 ml 2 time during treatment course with interval for 5 days, wherein total treatment course includes 10 days.
EFFECT: method with simultaneous antioxidant, antitoxic, metabolism stimulating, and liver function normalizing action.
2 ex, 3 tbl
FIELD: medicine, vitamins.
SUBSTANCE: invention proposes a composition of vitamins riboflavin and nicotinic acid (niacin) or nicotinamide for treatment of primary headaches representing usual migraine, classic migraine, migraine combined with "histamine" headache. The composition comprises the combination of 0.5-750 mg of nicotinic acid (niacin or nicotinamide) and 0.1-250 mg of riboflavin. Also, the invention involves the corresponding method for treatment. Proposed treatment provides body with necessary NAD/NADP and FAD/FMN in order to modulate activity of mast cells when changes in their secretion results to migraine. Method provides disappearance of all migraine symptoms during the next 20 months of dispensary observation.
EFFECT: enhanced medicinal effectiveness of vitamins.
FIELD: pharmaceutical industry.
SUBSTANCE: claimed complex contains vitamins such as B1, B2, B3 (nicotineamide), B5 (calcium pantothenate), B6, B9 (folic acid), B12, A, C, D3, E, beta-carotene, lycopitin, and minerals such as magnesium, copper, iodine, iron, molybdenum, selenium, calcium, phosphorus, chromium, zinc, and manganese. Complex is separated into two solid formulations taken at different time. The first solid formulations contains B1, B2, B3 (nicotineamide), B5 (calcium pantothenate), B6, B9 (folic acid) and minerals such as magnesium, copper, iodine, iron, molybdenum in specific component ratio; the second one contains A, C, D3, E, beta-carotene, lycopitin, and minerals such as selenium, calcium, phosphorus, chromium, zinc, and manganese in specific component ratio.
EFFECT: vitamin-and-mineral complex of improved antioxidant properties.
6 cl, 1 ex
FIELD: pharmaceutical industry.
SUBSTANCE: invention relates to creation of therapeutical and prophylactic balsams, which can be used as generally restorative and tonic agents to increase resistance of organism to reduced levels of atmosphere oxygen (increase of hypoxia resistance) as well as to prevention and correction of functional disorders associated with stress and exhausting environmental factors affecting organism. Invention proposes two variants of therapeutical-prophylactic balsam producing generally restorative and tonic effects, each containing vegetable oils, vitamins, amino acids, hepatic implant cells (Hepatosan), adaptogen (Astragerm), antioxidant, odorant, and thickener.
EFFECT: achieved normalization of vitality in exhausted organism.