Treatment of aspergillosis in rabbits
(57) Abstract:The invention relates to veterinary medicine, in particular to methods for treating visceral mycosis rabbits, caused by a pathogenic fungus of the genus Aspergillus fumigatus. The technical result - the simplification of the way when the extension class of drugs for the treatment of aspergillosis rabbits. The method is as follows. Preparing a medicinal product with a content of 100 mg of mebendazole in 1 ml of water, the drug is administered to rabbits in a volume of 2-3 ml subcutaneously in the shoulder area once a day for 2-3 days in a row on 2-3rd day from the disease. 1 C.p. f-crystals, 4 PL. The invention relates to veterinary medicine, in particular to methods for treating visceral mycosis rabbits, caused by a pathogenic fungus of the genus Aspergillus fumigatus.Currently, there is a method of treatment of aspergillosis with mass lesions using aerosols containing iodine preparations. The aerosol is sprayed into the room at 1 m320 ml of 0.5% solution of iodine within 5-6 days (see Treatment and prevention of aspergillosis. C. C. Petrovich in the book. Mycosis animals. Moscow. Rosagropromizdat, 1989, S. 93).However, therapeutic efficacy of this drug are minor, the method is General introduction nystatin dose 10000-15000 UNITS per 1 kg of live weight 3-4 times daily for 7-9 days in a row (see Worms D. K. Evdokimov P. D. Wicker A. S. Drugs in veterinary medicine, M. Kolos", 1966, S. 322-323).However, the application of nystatin with aspergillosis ineffective, because nystatin is mainly on yeast-like fungi, practically not absorbed from the gastrointestinal tract. In addition, the treatment course is long.Closest to the claimed technical solution is a method of treatment of aspergillosis with use as a medicinal product 30% solution of sodium thiosulfate and 20% solution of caffeine sodium benzoate. Sodium thiosulfate is administered 2 times a day for two days in a row for 20-30 ml inside, and caffeine sodium benzoate injected once a day for 5-10 ml (see Microflora of concentrated feed and toxicosis fungi of the genus Aspergillyus. I., Arrests, M. A. Hantuchova, in Proc. of the scientific, Tr. Pharmacology and toxicology of new drugs and feed additives in veterinary medicine. Leningrad, 1990, S. 96-98).However, this method is time-consuming, as it involves the combination of a specific therapy with symptomatic treatment. In addition, the introduction of a solution of sodium thiosulfate inside the difficult doable.The technical result of the simplification of the way when expanded the query result is achieved by in the treatment of aspergillosis, which consists in the introduction of a medicinal product, as the last drug use on the basis of mebendazole, which is injected subcutaneously once a day 2-3 days 2-3 days from the day of disease at a dose of 200-300 mg/goal.As a preparation on the basis of mebendazole may be used either vermox or mibenum or megamin.Vermox or mebendazole drug formula C16H13H3O3or methyl-5-benzylbenzimidazole-2-carbamate white slightly yellowish powder, practically insoluble in water and in most organic solvents. In the formic acid soluble. Molecular weight 295,29. Melting point 280oC (see, for example, the prospectus to the drug "Vermox" produced by the Chemical plant Gedeon Richter A. O. Budapest, Hungary).Drug megamin is a similar vermoxe, white (sometimes with a faint creamy or pinkish tinge) fine crystalline powder, odorless. Megamin is an anthelmintic drug is less toxic than vermox, does not mutagenic effect. Synthesized in I. M. P. and T. M. them. E. I. marcinkowskiego USSR Ministry of health and Institute of chemistry restaurantsin chemical-pharmaceutical plant. Form release 0.1 g 10 tablets in cellular packaging.Mibenum represents developed on the basis of mebenzadole antihelminthic drug specifically for vertical targets. The drug is produced by a Chemical plant Gedeon Richter A. O.In well-known authors of the sources of patent and scientific and technical information not described method of treatment of aspergillosis by introducing a medicinal product on the basis of mebendazole (vermox, madamina or melanota). The mechanism of action of these drugs is based on the effect of mebendazole on helminths. This mebendazole both in vitro and in vivo prevents the absorption of glucose worms, and consumption of glucose mammals will not be affected even when used in high doses. (see sic Modical information brochure for Mebendasole; Lanssen Pharmacoutica H. V. Resarch Labora tories, Beerse, Belgium, 1972, I. Levai. Review of clinical pharmacological trial of mebendazole, 1974. Documentation of Chemical Plant Gedeon Richter (RGD 1647). Microscopic fungi of the genus Aspergillus for their carbohydrate metabolism intensively use large amounts of glucose. Given this feature of mushrooms for cultivation apply artificial nutrient medium, rich in carbohydrates (glucose and the Aspergillus due to the inability consumption of carbohydrates.The method is as follows.For the preparation of a medicinal product used an aqueous solution of madamina with a content of 100 mg of mebendazole in 1 ml of the Drug was administered to rabbits in a volume of 2-3 ml subcutaneously in the shoulder once a day 2-3 days 2-3 days from the day of disease.Rationale fungicidal activity, timing, and dose of drug is given below.Example 1. Rationale fungicidal activity of the drug.Sensitivity to Aspergillus vermox, mebeletu and megamenu was determined on agar Petri dishes using paper disks impregnated with solutions of the tested drugs and then placed on the surface of seeded aspergilloma agar. Records of the results of antifungal activity of the drugs was performed after 24, 48, 72 and 96 hours of cultivation of mushrooms at 37oC on the first day and at the 22oC in the following.The results of the antifungal activity of the tested drugs are presented in table. 1.Characteristic for Aspergillus growth on glucose agar noticeable after 24 hours of cultivation. To 48-72 hour of colony growth of the fungus fill the entire surface of the Cup.Disks impregnated pre is eriki growth Aspergillus was on cups with discs soaked madamina 30 mm. Thus, laboratory tests showed that the greatest fungicidal action had Madamin, the preparation of domestic production, more available for use in General practice.Example 2. The rationale for the introduction of optimal doses of the drug.To determine the optimal therapeutic doses of mebendazole was selected on the basis of analogues 38 rabbits, which were divided into 8 groups. The first 7 groups of experienced and 8th of control. Rabbits experimental groups were administered the drug in the following doses: 100, 150, 200, 250, 300, 350 and 400 mg/goal. 1 time per day 2-3 days. The animals were monitored for 7 days. Take into account for the duration and outcome of the disease. Rabbits died during the experience and murdered diagnostic purposes, examined postmortem and Ekologicheskie.Data of the experiment are given in table. 2.From the data table shows that the most optimal therapeutic doses of mebendazole at aspergillosis rabbits are 200-300 mg/goal.The introduction of the drug in a daily dose of 300 mg/goal leads to unnecessary costs, not increase therapeutic effect and increases the volume of injected drugs, rendering RA is the party died in the abdominal cavity is detected characteristic aspergilloma, the kidneys also stripped hemorrhage, bladder full of urine mixed with blood. In smears from aspergillum when using the microscope revealed the mycelium of the fungus of the genus Aspergillus.Example 3. Determining the optimal timing of the introduction of mebendazole in the treatment of aspergillosis rabbits shown in the table. 3, where on the basis of experimental data on the optimal timing and frequency of administration in 2-3 days after the onset of clinical signs of disease.Example 4. The choice of method of administration of the drug is shown in the data table. 4.These tables indicate that a significant difference in therapeutic efficacy of mebendazole at aspergillosis rabbits depending on the route of administration (subcutaneous or intramuscular) is not installed. We believe that the easiest to perform subcutaneous route of administration.All recovered animals 7 days after infection were killed. Pathological picture was normal, except for animals 4-1 group, have kidney detected a faint aspergilloma, seeding them onto medium gave a negative result.Thus, experimental studies on 61 kalekapisi fungi of the genus Aspergillus. The most effective was the domestic drug megamin.The test results indicate a positive therapeutic effect of the treatment of aspergillosis rabbits. 1. Treatment of aspergillosis in rabbits by injection of a medicinal product, characterized in that the quality of drug use drug-based mebendazole, which is injected subcutaneously once a day for 2 to 3 consecutive days for 2 3 day of the disease at a dose of 200 - 300 mg/goal.2. The method according to p. 1, characterized in that the quality of the drug on the basis of mebendazole use megamin.
< / BR>where n 0,2,5; R is allyl, dialkylamino or balance monocyclic saturated amine, which may contain an additional heteroatom R1and R2same or different: H, lower alkali, alkoxy or their pharmaceutically acceptable salts, which have a selective anxiolytic activity
to their pharmaceutically acceptable additive salts, and stereochemical isomeric forms, where a1AND2AND3AND4is a bivalent radical having the formula
-CH CH-CH CH- (a-1),
-N CH-CH CH- (a-2)
-CH N-CH CH- (a-3)
-CH CH-N CH- (a-4),
-CH CH-CH N- (a-5),
-N CH-N CH- (a-6) or
-CH N-CH N- (a-7), where one or two hydrogen atoms in said radicals (a-1) to(a-7) can be independently substituted by a halogen atom, a C1-C6-alkyl, C1-C6-alkyloxy, hydroxy, or trifluoromethyl; R represents hydrogen or C1-C4-alkyl; R1represents hydrogen, C1-C6-alkyl or hydroxy WITH1-C6-alkyl;
m is 1 or 2;
represents a C1-C4-alcander; B is an R2CH2, O, SO or SO2where R2is hydrogen or C1-4-alkyl;
n is 0, 1 or 2;
L represents hydrogen; C1-2-alkyl; C3-6-cycloalkyl; C3-C6alkenyl, optionally substituted by aryl; C1-C6-alkylsulphonyl; C1-C6-алкилоксикBR>-Alк-Y-R4(o-2);
-Alк-Z1-C X-2-R5(o-3); or
-CH2-CHOH-CH2-O-R6(o-4); where R3represents cyano, aryl or Het; R4represents hydrogen, aryl, Het, or1-C6-alkyl, optionally substituted aryl or Het; R5represents hydrogen, aryl, Het or1-C6-alkyl, optionally substituted aryl or Het; R6represents aryl or naphthalenyl; Y represents O, S, NR7where R7is hydrogen, C1-C6-alkyl or C1-C6-alkylcarboxylic;
Z1and Z2each independently represents O, S, NR8or a simple link, where R8is hydrogen or C1-C6-alkyl; X represents O, S or NR9where R9is hydrogen, C1-C6-alkyl or cyano; Alк each independently is a C1-C6-Alcantara; each Het represents: (i) optionally substituted heterocyclic ring with 5 or 6 members containing 1, 2, 3 or 4 heteroatoms selected from oxygen, sulfur and nitrogen, provided that there is not more than 2 oxygen atoms and/or sulfur; (ii) optionally substituted heterocyclic ring with 5 or 6 members which of substituted five - or six-membered ring through 2 carbon atoms or 1 nitrogen atom; and that in the rest of the condensed ring contains only carbon atoms; (iii) optionally substituted heterocyclic ring with 5 or 6 members, which contains 1 or 2 heteroatoms selected from oxygen atoms, sulfur and nitrogen, and optionally substituted five - or six-membered ring through 2 carbon atoms or 1 carbon atoms and 1 nitrogen atom; and which in the rest of the condensed ring contains 1 or 2 heteroatoms selected from oxygen atoms, sulfur and nitrogen; and, if Het is a monocyclic ring system, it is not necessary to have up to 4 substituents; and if Het is a bicyclic ring system, it may not necessarily be up to 6 substituents, which are selected from halogen, amino, mono - and di(C1-C6-alkyl)amino, aryl WITH1-C6-amino, nitro, cyano, aminocarbonyl,1-C6-alkyl, C1-C6alkyloxy,1-C6-alkylthio,1-C6-allyloxycarbonyl,1-6-alkyloxy-FROM1-6-alkyl, C1-6-allyloxycarbonyl1-6-alkyl, hydroxy, mercapto, hydroxy1-C6-alkyl, C1-C6-alkylcarboxylic aryl, Rilc1-C6-alkylamino is whether 3 substituents, each of which is independently selected from halogen, hydroxy, nitro, cyano, trifloromethyl,1-C6-alkyl, C1-C6-alkyloxy,1-C6-alkylthio, mercapto, amino, mono - and di-(C1-C6-alkyl)amino, carboxyl,1-6-allyloxycarbonyl, and C1-C6-alkylcarboxylic
FIELD: medicine, oncology.
SUBSTANCE: the present innovation deals with treating patients with uterine cervix cancer with relapses in parametral fiber and in case of no possibility for radical operative interference and effect of previous radiation therapy. During the 1st d of therapy one should intravenously inject 30 mg platidiam incubated for 1 h at 37 C with 150 ml autoblood, during the next 3 d comes external irradiation per 2.6 G-r. During the 5th d of therapy one should introduce the following composition into presacral space: 60 ml 0.5%-novocaine solution, 1 ml hydrocortisone suspension, 2 ml 50%-analgin solution, 1 ml 0.01%-vitamin B12 solution, 1.6 g gentamycine, 800 mg cyclophosphan, 10 mg metothrexate. These curative impacts should be repeated at mentioned sequence four times. The method enables to decrease radiation loading and toxic manifestations of anti-tumor therapy at achieving increased percent of tumor regression.
EFFECT: higher efficiency of therapy.
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to a group of new derivatives of 4,5-dihydro-1H-pyrazole of the general formula (I):
wherein R means phenyl, thienyl or pyridyl and these indicated groups can be substituted with (C1-C3)-alkoxy-group or halogen atom; R1 means phenyl that can be substituted with (C1-C3)-alkoxy-group or pyridyl group; R2 means hydrogen atom or hydroxy-group; Aa means one group among the following groups: (i) , (ii) , (iii) , (iv) or (v) ; R4 and R5 mean independently from one another hydrogen atom or (C1-C8)-branched or unbranched alkyl; or R4 means acetamido- or dimethylamino-group or 2,2,2-trifluoroethyl, or phenyl, or pyridyl under condition that R5 means hydrogen atom; R6 means hydrogen atom at (C1-C3)-unbranched alkyl; Bb means sulfonyl or carbonyl; R3 means benzyl, phenyl or pyridyl that can be substituted with 1, 2 or 3 substitutes Y that can be similar or different and taken among the group including (C1-C3)-alkyl or (C1-C3)-alkoxy-group, halogen atom, trifluoromethyl; or R3 means naphthyl, and its racemates, mixtures of diastereomers and individual stereoisomers and as well as E-isomers, Z-isomers and mixture of E/Z-compounds of the formula (I) wherein A has values (i) or (ii), and its salt. These compounds are power antagonists of Cannbis-1 (CB1) receptor and can be used for treatment of psychiatric and neurological diseases. Except for, invention relates to a pharmaceutical composition used for treatment of some diseases mediated by CB1-receptor, to a method for preparing this composition, a method for preparing representatives of compounds of the formula (I) wherein Aa means group of the formulae (i) or (ii), intermediate compounds used for preparing compounds of the formula (I) and to a method for treatment of some diseases mediated by CB1-receptor.
EFFECT: valuable medicinal properties of compounds.
16 cl, 9 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new 1-(p-thienylbenzyl)-imidazoles of the formula (I): , wherein indicated residues represent the following values: R(1) means halogen atom, (C1-C4)-alkoxyl, (C1-C8)-alkoxyl wherein one carbon atom can be replaced with heteroatom oxygen atom (O); R(2) means CHO; R(3) means aryl; R(4) means hydrogen halogen atom; X means oxygen atom; Y means oxygen atom or -NH-; R(5) means (C1-C6)-alkyl; R(6) means (C1-C5)-alkyl in their any stereoisomeric forms and their mixtures taken in any ratios, and their physiologically acceptable salts. Compounds are strong agonists of angiotensin-(1-7) receptors and therefore they can be used as a drug for treatment and prophylaxis of arterial hypertension, heart hypertrophy, cardiac insufficiency, coronary diseases such as stenocardia, heart infarction, vascular restenosis after angioplasty, cardiomyopathy, endothelial dysfunction or endothelial injures, for example, as result of atherosclerosis processes, or in diabetes mellitus, and arterial and venous thrombosis also. Invention describes a pharmaceutical composition based on above said compounds and a method for their applying also.
EFFECT: valuable medicinal properties of compounds and composition.
10 cl, 19 ex
FIELD: organic chemistry and pharmaceutical compositions.
SUBSTANCE: invention relates to new 3-(5)-heteroaryl-substituted pyrazoles of formula I , tautomers or pharmaceutically acceptable salt of compounds and tautomers. In formula R1 is hydride, piperidinyl substituted with methyl, lower alkyl optionally substituted with halogen, hydroxyl, lower alkylanimo or morpholino; R2 is hydride, lower alkyl, amino, aminocarbonylamino, lower alkylaminocarbonylamino, lower alkylsulfonylamino, aminosulfonylamino, lower alkylaminosulfonylamino; Ar1 is phenyl optionally substituted with one or more independently selected halogen; HetAr2 is pyridinyl with the proviso that R2 is not amino or n-propyl when HetAr2 is pyridinyl; and HetAr2 is not 2-pyriridinyl when R2 is hydrogen or lower alkyl. Compounds of formula I have kinase p38 inhibitor activity and are useful in pharmaceutical compositions for treatment of various diseases.
EFFECT: new effective kinase p38 inhibitors.
23 cl, 6 dwg, 1 tbl, 1 ex
FIELD: veterinary science.
SUBSTANCE: a dog should be introduced with 4-[3-(difluoromethyl)-5-(3-fluoro-4-methoxyphenyl)-1H-pyrazole-1-il]benzene sulfonamide or its pharmaceutically acceptable salt at daily dosage ranged about 0.1-10 mg/kg body weight.
EFFECT: higher efficiency of therapy.
4 cl,262 ex, 12 tbl
FIELD: medicine, gynecology, anesthesiology.
SUBSTANCE: invention concerns to a method for carrying out the anesthesiology assistance for woman in childbirth with accompanying bronchial asthma. Method involves administration of atropine, dimedrol, analgin and clophelin. Method involves additional intravenous administration of transamine for 5-7 min. Transamine is administrated in doses 12-14 and 15-17 mg/kg in woman in childbirth with body mass 75 kg and above and 74 kg and less, respectively. Method provides enhancing quality and safety of anesthesia in this class of woman in childbirth.
EFFECT: improved assistance method.
7 tbl, 4 ex
FIELD: medicine, dermatology, chemical-pharmaceutical industry, pharmacy.
SUBSTANCE: invention relates to an antifungal gel pharmaceutical composition based on ketoconazole and clotrimazole that are derivatives of imidazole. The composition comprises ketoconazole or clotrimazole as an active component, polyethylene glycol-400 (PEG-400) as a solvent, carboxyvinyl polymer as a gel-forming agent, polyethylene glycol as a gel stabilizing agent, organic amine or inorganic bas as a regulator of pH and water taken in the definite ratio of components. The composition is prepared by dissolving active component in PEG-400, dispersing carboxyvinyl polymer in water, successive addition to dispersion propylene glycol as a stabilizing agent and regulator of pH and combination of prepared solution and gel followed by stirring the mixture up to preparing the gel composition with pH 5-7. Invention provides preparing antifungal composition with reduced adverse effect.
EFFECT: improved preparing method, valuable medicinal properties of composition.
2 cl, 1 tbl, 11 ex
FIELD: veterinary science.
SUBSTANCE: the present innovation deals with applying selector as a selenium-containing organic preparation to be introduced for cows and calves monthly intramuscularly at the dosage of 10 mcg/kg body weight. The method provides decreased fodder expenses for the synthesis of the production obtained.
EFFECT: higher productivity in cattle.
2 ex, 7 tbl
FIELD: organic chemistry, medicine, allergology, chemical-pharmaceutical industry, pharmacy.
SUBSTANCE: invention relates to a method for treatment of patient suffering with allergic disease. Method involves administration to patient the therapeutically effective dose of pharmaceutical composition comprising compound of the formula (I)
. The compound elicits high effectiveness in treatment of allergy and shows low toxicity also.
EFFECT: improved method for treatment.
9 cl, 2 tbl, 2 dwg, 40 ex
FIELD: veterinary science.
SUBSTANCE: one should apply a selenium-containing preparation named selecor: it should be introduced on the 80-90th d of swine gestation twice at 10-15-d-long interval parenterally at the dosage of 20 mg/kg animal body weight. Application of low-toxic antioxidant as selecor enables to improve functional properties of cell membranes of placental system and endometrium and increase inspecific immune resistance in sows. It, also, enables to increase fertility in sows, values of uncomplicated deliveries and puerperal period.
EFFECT: higher viability of off-spring.
2 ex, 3 tbl