Preparation possessing antitoxic activity and containing complex compound, methyluracil derivative with organic acid, and method for preparing it
SUBSTANCE: preparation shows an antitoxic activity, and can be used as an antidote for nitrite and nitrate poisoning. A complex compound of 5-hydroxy-6-methyluracil with ascorbic acid (5-hydroxy-6-methyluracil ascorbate) is described by formula: The preparation contains the complex compound in an amount of 0.3-0.4 wt %, and ascorbic acid - the rest. The method for producing the preparation consists in a reaction of 5-hydroxy-6-methyluracil and ascorbic acid taken in the relation of ascorbic acid: 5-hydroxy-6-methyluracil equal to 1:(0.0015-0.0022), in water as a solvent at a temperature of 20-40°C for 30-60 minutes. The complex compound is produced as shown by infra-red and NMR spectra. The antitoxic activity of 5-hydroxy-6-methyluracil on nitrite has been unknown before.
EFFECT: water removal from the reaction mixture under low pressure.
2 cl, 2 tbl, 1 ex
The invention relates to medicine, in particular to pharmacology, and drugs with antioxidant activity and containing the complex compound derived methyluracil with an organic acid, specifically compound 5-hydroxy-6-methyluracil with ascorbic acid (5-hydroxy-6-methyluracil ascorbate) formula:
This drug can be used as an antidote in the complex of therapeutic measures in the administration of nitrites and nitrates.
Known immunomodulatory drugs [patent RU 2292892, CL AC 31/513, AK 47/12, OR 37/04, publ. 10.02.2007,] containing diazepan (pair-pair-(2,4-Dioxo-6-methylpyrimidine-5-sulphonamido)-diphenylsulfone) or sulphite (N,N'-(Sulfonyl-1,4-phenylene)-bis-(N",N"-dimethylformamidine)-1,2,3,4-tetrahydro-6-methyl-2,4-dioxo-5-pyrimidinemethanol) and ascorbic acid in a ratio of components: diazepan (soliton)/acid=1,65/(1,0-0,5). These drugs exhibit high together with immunomodulating activity. However, both tools can only be used in the treatment of several diseases involving immune defficiency of the body, and the results of their research antitoxic no action.
Known compound 6-methyluracil with succinic acid, showing antigipoksicheskoe activity [patent RU 2259357, CL C07D 239/22, publ. 27.08.2005,]. This compound has a higher antihypoxic activity in comparison with reference drugs and low toxicity. The disadvantage is that information about the antitoxic action of this complex compound is absent. However, we can assume that its antitoxic effect will be less pronounced than in the claimed product, as antitoxic effect of 6-methyluracil is less pronounced than that of its derivative 5-hydroxy-6-methyluracil, and succinic acid is not among the antidotes for poisoning by nitrites and nitrates.
The closest to describing the technical essence and the achieved result is a drug that has antihypoxic activity and containing the complex compound derived methyluracil with an organic acid, the derivative methyluracil use of 1,3-bis(2-hydroxyethyl)-5-hydroxy-6-methyluracil, and as the organic acid is fumaric acid [patent RU 2330025, CL C07D 239/60, AK 31/513, A61P 9/10, publ. 27.07.2008,]. The complex compound has the formula:
The drug having antihypoxic activity and containing the complex compound derived methyluracil with an organic acid, obtained by the interaction of equimolar number of the qualities of 1,3-bis(2-hydroxyethyl)-5-hydroxy-6-methyluracil with fumaric acid in the environment of a solvent at a temperature of 60-70°C for 2-3 hours, removal of the solvent from the reaction mixture and obtain a product. As the solvent used ethanol. This compound compared with the reference drugs has a higher antihypoxic activity and low toxicity when injected into the stomach and intraperitoneally. However, the antitoxic action of complex compounds 1,3-bis(2-hydroxyethyl)-5-hydroxy-6-methyluracil with fumaric acid is not given.
The task, which directed the claimed technical solution is to expand the Arsenal of pharmacological agents with low toxicity, with higher antioxidant activity.
The problem is solved by obtaining the drug, possess antioxidant activity and containing the complex compound derived methyluracil with an organic acid, where as derived methyluracil used 5-hydroxy-6-methyluracil, the organic acid is ascorbic acid, and the product contains compound 5-hydroxy-6-methyluracil with ascorbic acid of the formula:
in the amount of 0.3-0.4% of the mass. and ascorbic acid - the rest.
A method of producing a drug that has antitoxic activity and containing the complex compound derived METI the uracil with an organic acid, is their interaction in the environment of the solvent, followed by removing the solvent from the reaction mixture and the product, as derived methyluracil using 5-hydroxy-6-methyluracil, the organic acid is ascorbic acid, and the solvent is water, the source reagents are taking in a molar ratio of ascorbic acid : 5-hydroxy-6-methyluracil 1:(0,0015-0,0022), the interaction is carried out at a temperature of 20-40°C for 30-60 minutes, and the solvent is carried out under reduced pressure.
It is known that ascorbic acid is used as antidote for poisoning by nitrite and nitrate, 5-hydroxy-6-methyluracil reduces the level of methemoglobin in mice when the administration of sodium nitrite.
Acute toxicity of the preparation was studied on white mice-males weighing 20±2 g Three animal groups of 10 animals each once in the stomach through a tube introduced the drug in doses of 2000 mg/kg, 4000 mg/kg and 6000 mg/kg (table.1). Observations of the animals were within two weeks. Take into account survival (mortality) mice, coat condition, physical activity, frequency of intake of food and water, reflex activity.
|Sharp shock, which was mentioned drug (composition: compound 5-hydroxy-6-methyluracil with ascorbic acid 0.3% wt., ascorbic acid 99.7% of the mass.) for white mice, various routes of administration in the body|
|A group of mice||Dose, mg/kg||The number of mice||The route of administration of medication||Survival, %|
|1||100||10||in the abdominal cavity||100|
|2||500||10||in the abdominal cavity||100|
|3||1100||10||in the abdominal cavity||100|
|4||2000||10||in the stomach||100|
|5||4000||10||in the stomach||100|
|6||6000||10||in the stomach||100|
|The influence of the drug (composition: compound 5-hydroxy-6-methyluracil with ascorbic acid is - 0.3% wt., ascorbic acid 99.7% of the mass.) on the lifespan of mice in a model of acute poisoning with sodium nitrite|
|Series of experience||Options experience||The number of mice||Life expectancy|
|1||Sodium nitrite||8||of 17.5||100|
|2||The drug, prophylactic administration||8||40,2||228,3||<0,001|
|3||Drug treatment introduction||8||22,0||125,7||<0,05|
|4||Ascorbic acid, prophylactic administration||8||32,5||185,6||<0,001|
|P* - significance level|
The drug is highly protective (preventive) activity in acute poisoning with sodium nitrite. The positive effect of ascorbic acid (200 mg/kg), recommended as an antidote to poisoning nitrite and nitrate, were less pronounced than the study drug.
therapeutic use of the drug compared with prophylactic less effective: the average life expectancy of poisoned mice by prophylactic administration to mice of the drug 40.2 min (228,3%), and therapeutic applications only 22,0 min (125,7%). Ascorbic acid in these conditions, the effect is not given.
The essence of the technical solution is illustrated by the following example.
Example 1. The synthesis of the drug.
To a solution of 2.5 g (0,0142 mol) of ascorbic acid in 50 ml of water was added 0,0031 g (0,000022 mol) of 5-hydroxy-6-methyluracil. The molar ratio of ascorbic acid : 5-hydroxy-6-methyluracil 1:0,0015. The reaction mixture was stirred for 40 minutes at 25°C. In the course of interaction was observed color change of the reaction mass. From the reaction mixture water was removed by evaporation under reduced pressure of 20 mm RT.article and obtained with a quantitative yield of product containing ascorbic acid and a complex compound 5-hydroxy-6-Metalurh the sludge with ascorbic acid. The preparation contains the compound 5-hydroxy-6-methyluracil with ascorbic acid in the amount of 0.3% of the mass. and ascorbic acid in the amount of 99.7% of the mass. The drug has a purple color.
Confirmation of the formation of complex compound data IR and13With NMR spectroscopy:
The IR spectrum of ascorbic acid, (v cm-1): 780, 1378, 1462 (furan ring), 1750 (RCOOR), 1198 (cyclic ether compounds), 1024, 1066, 1120, 1138 (C=O), 3214, 3310, 3406, 3528 (OH).
The IR spectrum of the complex compounds, (v cm-1): 760, 826, 874, 1024, 1042, 1366, 1402 (furan ring), 1636, 1654, 1684, 1756 (C=O, =N-C=O), 3016 (NH), 3214, 3316, 3406, 3526 (OH).
13From the NMR spectrum of ascorbic acid (δ M. D.): 62,10 (CH2OH); 70,61 (CHOH); 90,59 (C5); 160,37 (C2); 185,20 (C3); 194,76 (C4).
13From the NMR spectrum of the complex compounds (δ M. D.): 62,40 (CH2OH); 69,20 (CHOH); 77,10 (C5); 163,45 (C2); 128,60 (C3); 176,53 (C4).
The formation of the complex is confirmed by the shifts of the signals of the furan ring and the carbonyl group of ascorbic acid in IR and13From the NMR spectra.
The optimal condition for the creation of a drug that has antitoxic activity and containing the compound 5-hydroxy-6-methyluracil with ascorbic acid, is the temperature of 20-40°C and a duration of 30-60 minutes At temperatures below 20°C the speed of interaction between 5-hydroc and-6-methyluracil and ascorbic acid minor, and at temperatures over 40°C is the destruction of the complex compound 5-hydroxy-6-methyluracil with ascorbic acid. The interaction of reagents with a duration of less than 30 minutes is not enough for the formation of complex compounds, and process more than 60 minutes is impractical because of the additional time and energy costs.
The molar ratio of ascorbic acid : 5-hydroxy-6-methyluracil in the product is equal to 1:(0,0015-0,0022). This ratio is optimal, since the mixing ratio of ascorbic acid : 5-hydroxy-6-methyluracil < 1:0,0015 antitoxic action of the drug is weaker. By increasing the ratio of ascorbic acid : 5-hydroxy-6-methyluracil more than 1:0,0022 strengthening the antitoxic action of the drug is not observed, but at the same time increase the material cost of reagents.
From the reaction mixture water was removed by evaporation under reduced pressure, which allows the removal of water from the reaction mixture at temperatures below 40°C.
Thus, it follows from the presented results of the research, the proposed drug with antioxidant activity and containing the complex compound derived methyluracil with an organic acid, has more in the high antioxidant activity and low toxicity when injected into the stomach and intraperitoneally and allows you to expand the Arsenal of pharmacological agents with low toxicity, with a higher antioxidant activity.
1. The drug that has antitoxic activity and containing the complex compound derived methyluracil with an organic acid, characterized in that as a derivative methyluracil using 5-hydroxy-6-methyluracil, and as the organic acid is ascorbic acid, the preparation contains the compound of the following formula:
in the amount of 0.3-0.4% of the mass. and ascorbic acid - the rest.
2. The way to obtain the drug under item 1, with the use of interaction derived methyluracil with an organic acid in the environment of the solvent, followed by removing the solvent from the reaction mixture and the product, characterized in that as a derivative methyluracil using 5-hydroxy-6-methyluracil, the organic acid is ascorbic, and the solvent is water, the source reagents are taking in a molar ratio of ascorbic acid : 5-hydroxy-6-methyluracil 1:(0,0015-0.0022), the interaction is carried out at a temperature of 20-40°C for 30-60 minutes, and the solvent is carried out under reduced pressure.
SUBSTANCE: invention relates to a composition in the form of solid particles, including water-free crystalline 2-O-α-D-glucosyl-L-ascorbic acid, which includes 2-O-α-D-glucosyl-L-ascorbic acid in an amount, which is higher than 98.0% in the weight ratio, but less than 99.7% in the weight ratio, on the basis of a dry residue, which has a degree of crystallinity of water-free crystalline 2-O-α-D-glucosyl-L-ascorbic acid constituting 90% or more, counted on the basis of a diffraction image of X-rays for powder in the form of the said composition, which contains particles with the particle size, constituting less than 150 mcm, in the quantity, constituting 70 or more wt % of the entire disperse composition, and particles with the particle size, constituting at least 53 mcm, but smaller than 150 mcm, in the quantity, constituting from 40 to 60 wt % relative to the entire disperse composition, and which has a reducing ability of the entire composition, constituting less than 1 wt %. The said composition is used as a component of powder materials for food products, cosmetic preparations, therapeutic and preventive cosmetics and medications. The claimed invention also relates to a method of obtaining the claimed composition and to its application.
EFFECT: increased efficiency of the composition application.
11 cl, 7 dwg, 8 tbl, 7 ex
SUBSTANCE: novel chemical compound - L-ascorbate of 1-(2-hydroxyethyl)-4,6-dimethyl-1,2-dihydropyrimidin-2-one has the formula: According to tests conducted in multiple (course) application conditions in a dose of 20 mg/kg with an intraperitoneal administration method, data which indicate stimulation of physical performance of white laboratory rats were obtained.
EFFECT: high physical performance in sports medicine, labour environment and sports.
2 cl, 1 tbl
FIELD: food industry, cosmetics, pharmacy.
SUBSTANCE: invention relates to a method for preparing a stable product of solubilization of ascorbic acid in an aqueous solution using as a preserving or stabilizing agent. Product of solubilization (solubilizate) comprises ascorbic acid in the concentration up to 20 wt.-% and polysorbate as an emulsifier with value of hydrophilic-lipophilic balance from 9 to 18 taken in the amount up to 60 wt.-% and water up to 100%. Polysorbate-80 is used as emulsifier preferably. Solubilizate can comprise additionally α-tocopherol or mixed tocopherol. Also, octadecatrienoic, linolenic or oleic acids enhance stability of the supplement. Also, solubilizate consisting of ascorbic acid and emulsifier can comprise light vegetable oil, for example, thistle or flax oil consisting of triglycerides mainly. Preferably, a mixture consisting of 3 mass parts of indicated solubilizate with vegetable oil and 7 mass parts of tocopherol solubilizate is prepared. Aqueous ascorbic acid solubilizate and emulsifier (polysorbate) is prepared by addition of emulsifier to ascorbic acid aqueous solution followed by short-time heating at stirring up to attainment of clearness and homogeneity of the mixture. If necessary, light natural oil is added to ascorbic acid solution. Invention provides possibility for preparing ascorbic acid aqueous solutions as water- and oil-soluble capsulated formulation for prolonged storage.
EFFECT: improved preparing method.
21 cl, 6 dwg, 5 ex
enhance the body's resistance to the action of nitrogen dioxide and has cytoprotective and antihypoxant activity (N state of registration 10191991)
SUBSTANCE: invention relates to a novel complex of 5-hydroxy-6-methyluracil with sodium succinate (5-hydroxy-6-methyluracil succinate) of formula: , which exhibits antihypoxic activity. The disclosed compound widens the range of pharmacologically active compounds with low toxicity and high antihypoxic activity, which increase body resistance to certain types of hypoxia and in conditions influenced by other extreme environmental factors. The invention also relates to a method of producing the complex. The method involves mixing 5-hydroxy-6-methyluracil and sodium succinate in ratio of 1:10 in distilled water and then mixing the reaction mixture until dissolution of 5-hydroxy-6-methyluracil, removing the solvent from the reaction mixture and extracting the product.
EFFECT: output of the end product reaches 98%.
3 cl, 2 tbl, 4 ex
SUBSTANCE: invention refers to new biologically active high-immunotropic compound -N,N'-(sulphonyldi-1,4-phenylene)bis[(N",N'"-dimethyl)methyliminomethane]1,2,3,4-tetrahydro-6-methyl-2,4-dioxo-5-pyrimidinesulphonate of formula stated below to be used in treatment of, e.g., patients suffering from leprosy, allergic dermatosis, dermatitis herpetiformis. .
EFFECT: new compound is characterised with useful biological activity.
2 tbl, 1 ex
SUBSTANCE: invention relates to the new complex compound of 1,3-bis(2-hydroxyethyl)-5-hydroxy-6-methyluracil with fumaric acid of the formula which can be used in medicine as the substance capable of raising the survival rate in conditions under the influence of extreme environmental factors, particularly hypoxia. The new complex compound 1,3-bis(2-hydroxyethyl)-5-hydroxy-6-methyluracil with fumaric acid is obtained with 94% output by mixing equimolar quantities of 1,3-bis(2-hydroxyethyl)-5-hydroxy-6-methyluracil with fumaric acid in organic solvent with the subsequent heating of the reaction mixture for 2-3 hours, preferably at a temperature of 60-70°, removal of the solvent from the reaction mixture and the isolation of the product.
EFFECT: it makes it possible to increase the survival rate in harsh environmental conditions.
3 cl, 3 tbl, 5 ex
FIELD: organic chemistry, chemical technology.
SUBSTANCE: invention relates to the improved method for preparing 4,6-dimethoxy-2-(methylsulfonyl)-1,3-pyrimidine. Method involves reaction of 4,6-dichloro-2-(methylthio)-1,3-pyrimidine with alkaline metal methoxide in inert organic solvent, transfer of prepared 4,6-dimethoxy-2-(methylthio)-1,3-pyrimidine in aqueous acid medium and the following oxidation of this compound in the presence of catalyst if necessary, preferably, with an interphase catalyst, such as tricaprylmethylammonium chloride. Then method involves carrying out the purification stage wherein pH value of the aqueous acid reaction mixture is brought about to the value from 5 to 8 with aqueous base, such as alkaline metal hydroxide, for example, sodium hydroxide at temperature 10-90°C and stirring in the presence of absence of organic solvent, for example, aromatic hydrocarbon, such as benzene, toluene or isomeric xylenes, or alcohol, such as methanol or ethanol. Also, invention relates to using the prepared compound as an intermediate substance for synthesis of herbicide, in particular, 7-[(4,6-dimethoxypyrimidin-2-yl)thio]-3-methylphthalide by reaction of 7-mercapto-3-methylphthalide of compound in preparing herbicides, for example, 7-[(4,6-dimethoxypyrimidin-2-yl)thio]-3-methylphthalide.
EFFECT: improved preparing method.
24 cl, 2 sch, 1 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to 4,4'-sulfonyl-bis-(N,N'-dimethylammoniomethyleneaniline)-chloride, 6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonate of the formula (I) eliciting antibacterial, antimycobacterial and immunotropic activities. Also, invention describes a pharmaceutical composition based on compound of the formula (I).
EFFECT: valuable medicinal properties of compounds and composition.
3 cl, 7 tbl, 2 ex
FIELD: organic chemistry, biochemistry, pharmacy.
SUBSTANCE: invention relates to new heterocyclylsulfonyl alkylcarboxylic acids and their derivatives of the general formula (1): or their pharmaceutically acceptable salts, N-oxides or hydrates possessing the inhibitory effect on kinase activity and to the focused library for search of active leader-compounds comprising at least abovementioned compound. In the general formula 91) W represents optionally substituted heterocyclic radical, among them: pyrrole-3-yl, thiophene-2-yl, isooxazole-4-yl, pyrazole-4-yl, imidazole-4-yl, pyridine-3-yl, 1H-2,4-dioxopyrimidine-5-yl, 2,3-dihydro-1H-indole-5-yl, 2,3-dihydro-1H-indole-7-yl, 1,3-dihydro-2-oxoindole-5-yl, 2,3-dioxo-1H-indole-5-yl, 2-oxo-3H-benzoxazole-6-yl, benzothiazole-6-yl, 1H-benzimidazole-5-yl, benzo[1,2,5]oxadiazole-4-yl, benzo[1,2,5]thiadiazole-4-yl, 1,2,3,4-tetrahydroquinoline-6-yl, 3,4-dihydro-2-oxo-1H-quinoline-6-yl, quinoline-8-yl, 1,4-dihydro-2,3-dioxoquinoxaline-6-yl, 3-oxo-4H-benzo[1,4]oxazine-7-yl, 3-oxo-4H-benzo[1,4]thiazine-7-yl, 2,4-dioxo-1H-quinazoline-6-yl, 2,4-dioxo-1,5-dihydrobenzo[b][1,4]diazepine-7-yl or 2,5-dioxo-3,4-dihydrobenzo[b][1,4]diazepine-7-yl; Y represents optionally substituted methylene group; R1 represents chlorine atom, optionally substituted hydroxyl group, optionally substituted amino-group, optionally substituted azaheterocyclyl; n = 1, 2 or 3; or Yn represents carbon atom of optionally substituted (C3-C7)-cycloalkyl or optionally substituted (C4-C7)-heterocyclyl. Also, invention relates to a pharmaceutical composition in form of tablets, capsules or injections placed into pharmaceutically acceptable package.
EFFECT: valuable properties of compounds.
5 cl, 3 sch, 5 tbl, 6 ex
< / BR>where R denotes cyclopropyl, cyclobutyl, cyclohexyl, phenyl, unsubstituted or mono -, di - or tizamidine group selected from hydroxy, C1-C4of alkyl, C1-C4alkoxy, halogen, trifloromethyl, ceanography and amino groups; 1-or 2-naphthyl, 9-anthracene; 2-anthrachinone, Persil, unsubstituted or substituted group selected from1-C4of alkyl, C1-C4alkoxy, ceanography and halogen; 2-, 3 - or 4-chinoline, oxiranyl, 1-benzotriazolyl, 2-benzoxazolyl, furanyl, substituted C1-C4alkoxycarbonyl; C1-C4alkylsulphonyl or benzoyl; R1denotes halogen or1-C4alkyl, R2and R3independently represent hydrogen or C1-C4alkyl; X denotes an oxygen atom and Y represents an oxygen atom, a sulfur atom or a carbonyl, or their pharmaceutically acceptable salts, method of production thereof and pharmaceutical composition having antiviral activity, containing antiviruse-effective amount of compounds of General formula I
FIELD: veterinary medicine.
SUBSTANCE: invention is intended for treatment of acute poisoning of animals with neonicotinoid insecticides. The method comprises intravenous administration of diazepam, Ringer's solution and unitiol.
EFFECT: method improves effectively the survival of animals, reduces the concentration of neonicotinoid insecticides in the body.
3 tbl, 2 ex