A method of obtaining a substance that prevents nocturnal diuresis in young animals
(57) Abstract:Usage: the invention relates to the field of veterinary medicine, in particular to a method of obtaining the substance of prolonged action, preventing nocturnal diuresis in young animals. The essence of the invention lies in the fact that the use of atropine sulphate in tablet form, and before the introduction of tablet matrix 1 wt.h. atropine sulphate is mixed with 2-3 wt.h. hyaluronic acid and the mixture is dissolved in 10-20 wt.h. water, acidified to pH 3.0 to 4.0, with 80-100oC for 20-30 min, then the solution is cooled at 4-6oC for 2-4 h, add 3-4 volume of ethanol and the resulting precipitate is dried, as a filler to obtain tablets use lactose. table 1. The invention relates to the field of veterinary medicine, particularly to a method of obtaining the substance of prolonged action, preventing nocturnal diuresis in young animals.It is known that puppies, kittens and other Pets during the first year of life emit per night urine up to 5-7 times.There are various technical solutions aimed at creating drugs that prevent nocturnal diuresis young home is Oia.Closest to the claimed adopted for the prototype, is the composition in the form of tablets against bedwetting in young animals  containing as the active ingredient antimuskarinovoe act occurs substances, mainly sulphate of atropine in doses of 0.1-1.2 mg per tablet with a total weight of 0.3 gThe disadvantages of this drug lies in its multi-component nature (including, in addition to atropine sulphate, dried liver, glucose, yeast and cellulose), low efficiency (urine in animals for the night there 3-4 times), and its toxicity, expressed in dilated pupils, accommodation disorder, sleepiness, etc., due to individual sensitivity to atropine, present in the drug in free form 
The invention solves the problem of achieving prolonged effect of preventing nocturnal diuresis in young animals without any side effects.This result is achieved in that in the method of obtaining a substance that prevents nocturnal diuresis in young animals, including the use of atropine sulphate in the form of tablets, before introduction into the tablet matrix 1 wt.h. with the pH 3,0-4,0, at 80-100oC for 20-30 min, then the solution is cooled at 4-6oC for 2-4 h, add 3-4 volume of ethanol and the resulting precipitate is dried, as a filler to obtain tablets use lactose.The inventive method has the advantage over known in part to the fact that the use as an active ingredient proprietary atropine and its compounds with high molecular polysaccharide hyaluronic acid (GUK) can significantly improve the effectiveness of this alkaloid (urination in young animals for 8-10 hours a night time not noted), with the resulting substance is effective in lower doses (0.03 to 0.05 mg pills instead of 0.1-1.2 mg) and does not occur in animals inherent in the free atropine toxicity or side effects.It is important to emphasize that upon receipt of the substances according to the claimed method, atropine fully associated with the molecule GUK, as evidenced by the negative reaction to this alkaloid, and its release from the matrix occurs gradually over a long period of time (8-10 hours) in the gradual hydrolytic cleavage of the links between atropine and HUK under deystvitelnoe acid dissolved in 10 ml of water, acidified with 0.1 G. of HCl to pH 3.0, when heated at 80oC for 20 min, the solution is cooled at 4oC for 2 h, then diluted with water pH 3.0 to the original volume (10 ml), add 30 ml (3 volume) of ethanol, the precipitate is separated by filtration through a filter paper, dried at 40oC in vacuum and get 3 g (yield 100%) of powder contains 1 g of atropine sulfate, every 0.09 mg which is mixed with 299,1 mg of lactose and subjected to direct compression. Get 33333 tablets (atropine sulphate per tablet 0.03 mg), feeding them on one piece of young puppies or kittens prevents urination for 8-10 hrs of the night time without side effects.Example 2. A mixture of 1 g of atropine sulfate and 2.5 g of hyaluronic acid are dissolved in 15 ml of water, acidified with 0.1 G. of HCl to pH 3.5, at 90oC for 25 min, the solution is cooled at 5oC 3 h, adjusted to 15 ml water, pH 3.5, add to 52.5 ml of ethanol (3.5 volume), the precipitate was separated by filtration, dried at 40oC in vacuum and obtain 3.5 g (yield 100%) of powder contains 1 g of atropine sulfate, 0.14 mg every which mixed with 299,86 mg of lactose and subjected to direct compression. Get 25000 tablets (atropine sulfate in tablets is about time without side effects.Example 3. A mixture of 1 g of atropine sulfate and 3 g of hyaluronic acid was dissolved in 20 ml of water, acidified with 0.1 G. of HCl to pH of 4.0 at 100oC for 30 min, the solution is cooled at a 6oC 4 h, adjusted to 20 ml water, pH to 4.0, add 80 ml of ethyl alcohol (4 volume), the precipitate was separated by filtration, dried at 40oC in vacuum and get 4 g (yield 100%) of powder contains 1 g of atropine sulfate, every 0.2 mg which is mixed with 299,8 mg of lactose and get 20000 tablets by direct pressing (the content of atropine sulfate per tablet 0.05 mg), feeding them one tablet of young animals prevents urination for 8-10 hrs of the night time without side effects.Comparative analysis of technical and economic performance of the proposed method and the known method presented in the table.Thus, the proposed method allows to obtain a substance that prevents nocturnal diuresis in young animals 3.3-3.4 times smaller doses than by a known method, and does not cause toxic or side effects.As filler lactose has the advantages over starch and dextrins that, first, it has a more pleasant taste and, secondly, it outsa (not worse) during processing and storage.The sources of information.1. U.S. patent N 2594296, 1952.2. U.S. patent N 3062720, 1962.3. U.S. patent N 3063901, 1962.4. U.S. patent N 3923990, 1975.5. U.S. patent N 5075312, 1991 (prototype).6. Mashkovsky M. D. Medicines. M. Medicine, 1984, T. 1, 233.0 sec. A method of obtaining a substance that prevents nocturnal diuresis in young animals, including the mixing of sulphate of atropine with filler followed by manufacture of tablets, characterized in that before the introduction of tabletow matrix 1 wt.h. atropine sulphate is mixed with 2 to 3 wt.h. hyaluronic acid and the mixture is dissolved in 10 to 20 wt.h. water, acidified to pH 3 to 4, when 80 100oC for 20 to 30 minutes, after which the solution is cooled to 4, 6oC for 2 to 4 hours, add 3 to 4 volumes of ethanol and the resulting precipitate is dried, and the filler used lactose.
where R1represents hydrogen, lower alkyl, lower alkenyl, lower quinil, aryl lower alkyl, cycloalkyl lower alkyl, lower alkoxy lower alkyl, hydroxy lower alkyl, amino lower alkyl, mono - or di-lower alkyl, amino lower alkyl, formyl, lower alkylsulphonyl, amino lower alkylsulphonyl, lower alkoxycarbonyl, mono - or di-aryl-substituted lower alkyl, arylcarbamoyl lower alkyl, aryloxy lower alkyl, or lower alkylene
< / BR>X represents O or S;
W represents hydrogen, halogen, hydroxy, lower alkoxy, aryl lower alkoxy, nitro, trifluoromethyl or
< / BR>where R3represents hydrogen, lower alkyl or aryl lower alkyl, and R4represents lower alkyl or aryl lower alkyl; or alternatively the groupas a whole represents the
< / BR>R5is hydrogen, lower alkyl, aryl or aryl lower alkyl; and
< / BR>where B is one of the divalent residues and) g)
< / BR>and
X, l, m, n and R1R7have the following meanings:
X Gruppen or, if B denotes the divalent residue (a), a nitrogen atom,
l integer 1, 2 or 3,
m is an integer 1 or 2,
n is an integer of 1 to 4,
R1a hydrogen atom or an unbranched or branched alkyl with 1 to 6 carbon atoms,
R2a hydrogen atom, an unbranched or branched alkyl with 1 to 8 carbon atoms, unbranched or branched alkenyl with 4 to 6 carbon atoms, cycloalkyl with 3 to 7 carbon atoms, unsubstituted or substituted by alkyl with 1 to 3 carbon atoms, substituted, phenyl, unsubstituted or substituted by one or two methyl groups or methoxypropane or one halogen atom, or phenylalkyl with 1 to 3 carbon atoms in the alkyl part, unsubstituted or substituted at the fragrance stands or methoxy group or a halogen atom,
R3and R4the same or the difference is,
R5a hydrogen atom or a chlorine or methyl,
R6and R7the same or different and denote hydrogen atoms or alkali with 1 to 3 carbon atoms, and, in addition, R7may also indicate a halogen atom,
mixtures of their isomers or their individual isomers and their salts, mainly their physiologically tolerated acid additive salts, in particular with pharmacological action
FIELD: medicine, phthisiology.
SUBSTANCE: one should lymphotropically introduce the mixture of 5.0 ml 0.25%-novocaine solution and 2.0 ml 1%-dioxidine solution or the mixture of 5.0 ml 0.25%-novocaine solution and 0.5 g cefazoline subcutaneously into jugular cavity and deeply behind xiphoid process, successively 1 point once daily, 5-7 injections/course. After injection the site of injection should be treated either with heparin ointment or ultrasound (1-3 MHz, PPM 0.2 W/sq. cm, for 2 min, through Vaseline oil) followed by evaluating roentgenological dynamics of the process 10-14 d later.
EFFECT: higher efficiency of differential diagnostics.
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention describes benzamidine derivatives of the general formula (I): wherein R1 means hydrogen atom, halogen atom, (C1-C6)-alkyl or hydroxyl; R2 means hydrogen atom or halogen atom; R3 means (C1-C6)-alkyl possibly substituted with hydroxy-group, alkoxycarbonyl-(C3-C13)-alkylsulfonyl, carboxy-(C2-C7)-alkylsulfonyl; each among R4 and R5 means hydrogen atom, halogen atom, (C1-C6)-alkyl possibly substituted with halogen atom, (C1-C6)-alkoxy-group, carboxy-group, (C2-C7)-alkoxycarbonyl, carbamoyl, mono-(C2-C7)-alkylcarbamoyl, di-(C3-C13)-alkylcarbamoyl; R6 means heterocycle or similar group; each among R7 and R8 means hydrogen atom, (C1-C6)-alkyl or similar group; n = 0, 1 or 2, or their pharmacologically acceptable salts, esters or amides. Compounds elicit the excellent inhibitory activity with respect to activated factor X in blood coagulation and useful for prophylaxis or treatment of diseases associated with blood coagulation.
EFFECT: improved method for prophylaxis and treatment, valuable medicinal properties of compound.
26 cl, 2 tbl, 253 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention describes diazepane derivative of the general formula (I)
or its pharmaceutically acceptable salt wherein ring B means phenyl; ring A means pyridyl substituted with halogen atom optionally, or phenyl substituted optionally with lower alkyl, lower alkoxy-group or halogen atom; X1 represents -C(=O)-NR2- or -NR2-C(=O)- wherein R2 means hydrogen atom; X2 represents -C(=O)-NR3- or NR3-C(=O)- wherein R3 means hydrogen atom; R represents hydrogen atom or halogen atom; R1 means lower alkyl. Also, invention relates to a pharmaceutical composition and inhibitor of blood coagulation activated factor X that can be used for prophylaxis and treatment of patients suffering with thrombosis or embolism.
EFFECT: valuable medicinal properties of compound.
5 cl, 5 tbl, 6 ex
FIELD: organic chemistry, medicine, oncology, pharmacy.
SUBSTANCE: invention relates to a new pentacyclic compound derivative of taxane represented by the formula:
wherein R1 represents dimethylaminomethyl group or morpholinomethyl group; R2 represents halogen atom or alkoxy-group comprising from 1 to 6 carbon atoms, or its salt eliciting an antitumor effect, and to a medicine agent based on its. Invention provides preparing new derivatives of taxane eliciting the valuable biological effect.
EFFECT: valuable medicinal properties of compound.
13 cl, 1 dwg, 4 tbl, 16 ex
FIELD: organic chemistry, cardiology, pharmacy.
SUBSTANCE: invention describes compounds of the formula (I)
wherein R1, R2, R3 and Ra-Rh have values given in the description. Proposed compounds are useful in prophylaxis and treatment of arrhythmia, in particular, atrial and ventricular arrhythmia, Also, the invention relates to methods for preparing compounds of the formula (I) and intermediate compounds.
EFFECT: valuable medicinal properties of compounds.
41 cl, 1 tbl, 8 ex
SUBSTANCE: the present innovation deals with preventing hemodynamic complications at restoring circulation in a prolongly ischemized limb, or due to premeditated tourniquet application during operative interference. For this purpose, 5-12 min before the onset of circulatory restoration it is necessary to start intravenous injection of antihistamine and glucocorticosteroid preparations, followed by drop-by-drop infusion of inhibitors of proteolytic enzymes which should be continued after tourniquet removal, as well. The method provides tourniquet shock and tourniquet shock-associated complications along with developing the chance for increasing the duration period of operation.
EFFECT: higher efficiency of prophylaxis.
FIELD: organic chemistry, chemical technology, medicine, pharmacy.
SUBSTANCE: invention describes bicyclic N-acylated imidazo-3-amines or imidazo-5-amines salts of the general formula (I): wherein R1 means tert.-butyl, 1,1,3,3-tetramethylbutyl, (C4-C8)-cycloalkyl, phenyl disubstituted with (C1-C4)-alkyl, -CH2Ra wherein Ra means the group -CO(OR') wherein R' means (C1-C8)-alkyl; R2 means hydrogen atom, the group -CORb wherein Rb means (C1-C8)-alkyl or (C3-C8)-cycloalkyl; R3 means (C1-C8)-alkyl, (C3-C8)-cycloalkyl, phenyl, pyridyl, furfuryl or thiophenyl; A means tri-linked fragment of ring of the formula: wherein R6 and R7 mean hydrogen atom or tetra-linked fragment of ring of the following formulae: wherein R4' means hydrogen atom or benzyloxy-group; R5' means hydrogen atom; R6' means hydrogen atom, (C1-C8)-alkyl or nitro- (NO2)-group; R7' means hydrogen atom, (C1-C8)-alkyl, or R6' and R7' mean in common the following fragment of ring: -CRi=CRj-CH=CH- wherein Ri and Rj mean hydrogen atom; R5'' means hydrogen, chlorine atom or (C1-C8)-alkyl; R6'' means hydrogen atom; R7''n means hydrogen atom, amino- (NH2)-group or (C1-C8)-alkyl; R4''', R6''' and R7''' mean hydrogen atom; R8 means (C1-C8)-alkyl or (C3-C8)-cycloalkyl; X means anion of inorganic or organic acid, or their acid-additive compounds. Also, invention relates to a method for their preparing and a pharmaceutical composition based on thereof. These new compounds show affinity to opiate μ-receptor and can be used, in particular, as analgesic agents.
EFFECT: improved preparing method, valuable medicinal properties of compounds and pharmaceutical compositions.
12 cl, 2 dwg, 32 ex
FIELD: organic chemistry, biochemistry, pharmacy.
SUBSTANCE: invention relates to new derivatives of β-carboline of the general formula (I)
showing properties of phosphodiesterase V inhibitor (PDE V). In the general formula (I) R1 means hydrogen atom; n = 0; X is taken among the group consisting of oxygen (O), sulfur (S) atoms and NRD; R2 is taken among the following group: phenyl (that can be optionally substituted with 1-3 RB), 6-membered nitrogen-containing heteroaryl and 5-6-membered heterocycloalkyl comprising 1-2 oxygen atoms and condensed with benzene ring (optionally substituted with 1-3 RB); R4 is taken among the group consisting of hydrogen atom, carboxy-group. (C1-C6)-alkylcarbonyl, di-[C1-C8)-alkyl]-aminoalkoxycarbonyl, di-[(C1-C8)-alkyl]-amino-(C1-C8)-alkylaminocarbonyl; a = a whole number from 0 to 1; Y is taken among the group consisting of -CH2, -C(O); Z is taken among the group consisting of -CH2, -CHOH, and -C(O) under condition that when Z represents -CHOH or -C(O) then X represents -NH; is taken among the group consisting of naphthyl, 5-6-membered heteroaryl comprising 1-3 heteroatoms taken among nitrogen, oxygen and/or sulfur atoms possibly condensed with benzene ring; m = a whole number from 0 to 2; R3 is taken independently among the group consisting of halogen atom, nitro-group, (C1-C8)-alkyl, (C1-C8)-alkoxy-group, trifluorophenyl, phenyl (optionally substituted with 1-3 RB), phenylsulfonyl, naphthyl, (C1-C8)-aralkyl, 5-6-membered heteroaryl comprising 1-3 nitrogen atoms in the ring (optionally substituted with 1-3 RB). Also, invention relates to a pharmaceutical composition, a method for its preparing and methods for inhibition of phosphodiesterase V activity (PDE V), and for increase of the cGMP concentration.
EFFECT: improved preparing method, valuable medicinal and biochemical properties of compounds and composition.
14 cl, 11 sch, 7 tbl, 13 ex
FIELD: organic chemistry, pharmacy.
SUBSTANCE: invention relates to new pharmaceutical compositions comprising bicyclic compound of the formula (I): wherein A means -COOH or their functional derivative; X1 and X2 mean hydrogen or halogen atom; V1 and V2 mean carbon atoms; W1 and W2 mean groups and wherein R4 and R mean hydrogen atom, hydroxy-group; Z means carbon, oxygen, sulfur or nitrogen atom; R1 means saturated or unsaturated bivalent (C1-C10)-aliphatic hydrocarbon residue; R2 means saturated or unsaturated (C1-C10)-aliphatic hydrocarbon residue; R3 means hydrogen atom and glyceride. Also, invention relates to a method for stabilizing compositions and novel bicyclic compounds. Invention provides enhancing stability of pharmaceutical composition based on its dissolving in glyceride.
EFFECT: improved and valuable properties of compositions, improved stabilization of compositions.
42 cl, 8 tbl, 8 ex
FIELD: medicine, neurology, virology.
SUBSTANCE: invention relates to treatment of neurological diseases caused by herpes virus, such as Bell's paralysis, Hunt's disease, herpetic encephalitis accompanying with damage of cerebral nerves. Invention involves using 1,4-dihydropyridine blockers of calcium channels, such as felodipine, nifedipine, nimodipine, nisodipine being taken preferably in combination with herpes virus antagonist. Invention provides repairing damaged cerebral nerves by topical expanding arteriols and recovery of local microcirculation based on specific competitive interaction of definite groups of calcium blockers of 1,4-dihydropyridine type with vasoconstrictor endothelin.
EFFECT: enhanced effectiveness of treatment.
47 cl, 2 dwg, 1 ex