(57) Abstract:The invention relates to medicine and used to replenish the Arsenal of normalizing the immune status of the organism. The purpose of the invention is the use of anti-inflammatory and antimicrobial agent - chlorazol for a new purpose as an immunomodulator in particular in chronic bronchitis, impaired immune status, thereby increasing the effectiveness of therapy, normalization of immunological parameters and reduction of terms of treatment of patients. Chlorazol assigned to 1 tablet (0.1 g) 3 times a day for 14 days. Compared with a known immunomodulator (levamisole)chlorazol has not only immunokorrigiruyuschy, but also anti-inflammatory and antimicrobial effect. Unlike the levamisole chlorazol not toxic. The invention relates to medicine and used to replenish the Arsenal of normalizing the immune status of the organism.The purpose of the invention is the use of anti-inflammatory and antimicrobial agent - hatzala for a new purpose as an immunomodulator, thereby increasing the effectiveness of therapy in patients with impaired immunity, normalize immune responsive ness going down the ü within 14 days. Compared with a known immunomodulator - levamisole, frequently causing toxic side effect, chlorazol non-toxic and virtually no contraindications for its use by immune disorders. Chlorazol unlike levamisole has a positive effect not only on the T-system, but also In the immune system.P R I m e R 1. Patient C., 40 years old (case history N 398 for 1984). Complaints about constant cough with phlegm (up to 30 ml per day), shortness of breath on mild exertion, periodically shortness of breath, chest pain, intermittent, stabbing pain in the heart, headaches. The disease has developed gradually, gradually appeared cough, shortness of breath during physical activity. In 1978, the patient was diagnosed with chronic bronchitis. In subsequent years, the disease continued to progress. Heredity is not burdened.At the examination: normostenik, redundant power, moderate acrocyanosis. Chest expanded, mainly in the front-back dimension, the lower border of the lung is omitted. Over light percussion is determined by the sound box. Auscultation - hard breathing. Heard a lot of dry, mostly treble is s, rhythmic emphasis of the P-th tone on the pulmonary artery. AD - 140/90 mm RT.article The abdomen is soft, painless. Liver and spleen not palpable.Radiography and fluoroscopy chest: figure lungs diffuse moderately enhanced. Lesions not identified. The roots extended, sealed. Lung fields increased transparency. The excursion of the diaphragm of small amplitude. Heart, small size, waist smoothed aorta sealed, rhythmic pulsations.Spirography: sample tiffe 48%, FEV132,6%.Pneumotonometry: inspiratory flow 4.0 l/C, expiratory flow rate of 3.8 l/sECG: sinus tachycardia. Blockade of the right bundle branch.Analysis of the urine unchanged.The analysis of a blood: erythrocytes 4,41012/l, hemoglobin 146 g/l, color index of 1.0; leukocytes 5,2109/l, eosinophils 1%, stab neutrophils 3%, segmented neutrophils 65%, monocytes 2%, lymphocytes 29%, erythrocyte sedimentation rate of 2 mm/hTotal protein serum: 8 g/l, albumin of 48.5%; globulins:17,1%, 211,3%, 13.3%, AND 19.8 PER CENT, AND/G TO 0.9. C-reactive protein (++). Sialic acid 240).ed.The immune status: T-ROCK 50% (normal 60-70%), the absolute number 0,54109/l (norm 1-1,3109/l). In ROCK 7% (the a <35%), vitaminsvitamin ROCK 6 % (normal <5% ). T-helpers (teilinstitut) 39% (normal >45% ), T-suppressor (theophyllinevenlafaxine) 13% (usually 5-10%), RTML with PHA 0,75 (normal <0,65). Sensitization (RTML) to pneumococcus-0.6, immunoglobulins a, M, G - normal.Thus, the patient revealed violations mainly in the T-system of immunity (reduction in the number and functional activity of T-lymphocytes, bilateral changes in the subpopulations of T-lymphocytes).Clinical diagnosis: chronic obstructive bronchitis. Moderate asthmatic symptoms. Emphysema I-II century Pulmonary insufficiency II Art.The patient on the background of General medical complex (expectorant medicine, inhalation broncholytics,/R-R of aminophylline 2,4% - 10 ml LFC) was conducted treatment hatzala (0.1 g 3 times a day before meals for 14 days). A week later, after treatment of the patient, the less likely he was troubled by cough, shortness of breath have decreased, rarely observed shortness of breath. 2 weeks after course of treatment the patient sputum almost not allocated, cough appeared periodically.Auscultation was determined few bass dry rales. In dynamics has improved funkcjonalne normalization of immune status: T-ROCK 64%, the absolute number 1,25109/l-ROCK 8%, the absolute number 0,16109/l; active ROCK 26%, teilinstitut ROCK 59%, theophyllinevenlafaxine ROCK OF 2.5%, RTML with PHA 0,6.Microbial sensitization (-).Thus, in a patient with chronic obstructive bronchitis with symptoms secondary immunodeficiency inclusion in the medical complex of a course of treatment hatzala (14 days)contributed to clinical improvement, reduction of terms of treatment resulted in normalization of immune status (increase in absolute and percentage of T - and b-lymphocytes, a decrease in active ROCK, increased T-helper cells, decreased T-suppressors, improvement of the functional status of T-cells in response to PHA, the microbial reduction sensitization).P R I m m e R 2. Patient G., 59 years old (case history N 1046 for 1984). Complaints about constant cough with phlegm (up to 40 ml per day), shortness of breath with little exertion, poorly tolerates various smells, shortness of breath. Considers himself sick about 9 years. Heredity is not burdened.At the examination: normostenik, proper nutrition, moderate acrocyanosis. Nail plate the fingers resemble a watch glass. Piles is schultzii - diminished breath in individual sectors hard. Heard in moderation scattered dry rales, mostly treble; right under the blade - sounding fine-bubble wheezing. Borders of the heart is within normal limits. Muffled heart sounds, clean, rhythmic, small accent of II tone on the pulmonary artery, HELL 140/90 mm RT. Art. the Abdomen is soft, painless on palpation. Liver and spleen not palpated.Radiography and fluoroscopy chest: figure lungs diffuse strengthened vessels strain. To the right a few petrifikatov, the roots of a wide, dense. Sinuses sealed pleural adhesion. Lung fields increased transparency. The excursion of the diaphragm of small amplitude. Heart and vessels normal. The rhythmic pulsation of the heart.Spirography: VC/ANNUALLY for 72.8% of the sample tiffe 37,7%, FEV137,4%, residual air 53,8%.Pneumotonometry: inspiratory flow of 2.6 l/s, expiratory flow rate of 1.1 l/sECG - signs of strengthening the potentials of the left ventricle.Sputum analysis: purulent mucous, viscous consistency, there are crystals Charcot-Leyden, many eosinophils, a small number of cells, the epithelium of the bronchi places, alveolar cells in heaven is Liz blood: erythrocytes 4,91012/l, hemoglobin 160 g/l, color index 0,9; leukocytes 9,6109/l, eosinophils 9%, stab neutrophils 3% , segmented neutrophils 55% , lymphocytes 31%, monocytes 2%, ESR 11 mm/hThe immune status: T-ROCK - 83% , the absolute number 1,41109/l-ROCK of 2.0%, the absolute number 0,03109/L. Suppose T-ROCK: active ROCK - 52% , teilinstitut ROCK (helpers) - 65%, theophyllinevenlafaxine ROCK (suppressor) - 0%. Immunoglobulins a and M in the norm, G - 7.2 g/l (normal 9-18 g/l).Thus, the patient revealed mainly changes In the immune system (decreased numbers of b-lymphocytes and content of immunoglobulins G), and certain subpopulations of T-lymphocytes.Clinical diagnosis of chronic obstructive bronchitis in acute phase. Emphysema II Art. LN - II-III century Pulmonary heart in combination with atherosclerotic cardiosclerosis H1.On the background of the treatment (expectorants, inhalation broncholytics, 2.4% of R-R of aminophylline 10 ml intravenously, oxygen therapy) was administered a course of treatment hatzala (0.1 g 3 times a day for 14 days).As a result of the treatment showed positive dynamics. A week later feeling improve the was body temperature, reduced the number of wheezing has stopped the attacks of difficult breathing. After 2 weeks, decreased shortness of breath, cough became rare, the number of sputum decreased to 10-15 ml per day, sputum slimy character, lung auscultation rales were not determined. Improved respiratory function.Spirography: the number of 18 breaths in 1 minute, VC/ANNUALLY 86%. Residual air 39,3%; MOD 12,6 l; DMOD 4,9 l; IAL 34,0 l; DMWL 90,9 l; IAL/DMWL 37,3%; FEV143%.Pneumotonometry: inspiratory flow of 3.5 l/C, expiratory flow rate of 1.6 l/sAlong with clinical improvement noted positive changes in the immune status: normalized content of b-lymphocytes (B-ROCK 6%, the absolute number 0,1109/l) and the contents of certain subpopulations of T-ROCK (active ROCK 45%, helpers 58,5%, suppressor of 10.5%), increased the number of IgG (8,2 g/l).Thus, in a patient with chronic obstructive bronchitis with impaired immune status using chlorazol (14 days) significantly increased the effectiveness of the treatment (positive dynamics of subjective sensations and physical data, indicators of respiratory function) and had immunostimulatory (stimulation of In-system immunity is a mini examples illustrate immunostimulatory and immunomoduliruushimi properties hatzola, the absence of toxic side effects when using this drug.From these materials it follows that the use of chlorazol expands the Arsenal immunokorrigiruyuschy funds and significantly increases the effectiveness of therapy in patients with immune disorders. The use of chlorazol as immune-modulating means.
FIELD: organic chemistry, biochemistry.
SUBSTANCE: invention relates to epothilones with modified thiazole substituent, methods for production thereof and pharmaceutical composition capable of cell growth inhibiting containing the same. Claimed compounds have general formula I , wherein P-Q represents double carbon bond or epoxy; R represents H, C1-C6-alkyl; G represents ; R1 represents and ; G1 and G2 represent hydrogen; G3 represents O, S, and NZ1; G4 represents H, optionally substituted C1-C6-alkyl, OZ2, Z2C=O and Z4SO2; G5 represents halogen, N3, CN, NC, heteroaryl containing nitrogen or oxygen, and heterocycle; G6 represents H, C1-C6-alkyl, or OZ5, wherein Z5 represents H, C1-C6-alkyl; G9 represents oxygen; Z1 represents H, optionally substituted C1-C6-alkyl, optionally substituted acyl; Z2 represents optionally substituted C1-C6-alkyl or aryl; Z4 represents optionally substituted aryl.
EFFECT: new epothilones capable of cell growth inhibiting.
19 cl, 39 ex
FIELD: medicine, gastroenterology, pharmacy.
SUBSTANCE: invention relates to a solid composition eliciting with an anti-ulcer activity and to a method for its preparing. Pharmaceutical composition consists of a core containing famotidine as an active component and starch, aerosil, stearic acid salt as accessory inert substances wherein a core is covered by polymeric envelope. Core comprises glucose and stearic acid as an accessory inert substance and magnesium stearate as a stearic acid salt. Polymeric envelope comprises oxypropylmethylcellulose, propylene glycol, castor oil, talc and titanium dioxide taken in the definite ratio of all components in the composition. Method for preparing pharmaceutical composition involves preparing raw, mixing therapeutically effective amount of famotidine with glucose and starch, moistening the mixture with starch paste, granulation, drying wetted granulate, repeated granulation, powdering dry granules, tableting and applying polymeric envelope containing oxypropylmethylcellulose on prepared cores with addition of titanium dioxide, propylene glycol, castor oil and talc. Invention provides enhancement of degradability, solubility and stability in storing.
EFFECT: improved method for preparing, valuable pharmaceutical properties of composition.
3 cl, 1 ex
FIELD: organic chemistry, biochemistry, medicine, pharmacy.
SUBSTANCE: invention relates to methods for treatment of diseases or syndromes associated with metabolism of fatty acids and glucose and to new compounds and their pharmaceutically acceptable salts. Invention relates to applying new compounds and pharmaceutical compositions for treatment of cardiovascular diseases, diabetes mellitus, cancer diseases, acidosis and obesity by inhibition of activity of enzyme malonyl-CoA-decarboxylase. Indicated compounds correspond to formulae (I) and (II) wherein Y, C, R1, R2, R6 and R7 have values given in the invention claim.
EFFECT: valuable medicinal and biochemical properties of azoles.
27 cl, 8 tbl
FIELD: medicine, therapy, gastroenterology.
SUBSTANCE: method involves preliminary assay of the disorder type in gallbladder motor contraction and bile-excretion ways followed by prescribing thermal low-mineralized hydrocarbonate-sodium-sulfate-calcium-magnesium mineral water in the dose by 200-300 ml, 3 times per a day, 1 h before eating, tubages № 3 with mineral water, bathes and shower with mineral water every day for 10-14 days. In the hypotonic type of motor activity method involves mineral water at temperature 25-30°C, and in the hypertonic type - at temperature 38-40°C. Method provides accelerating in scars formation of ulcers and epithelization of erosions in gastroduodenal system, to prevent frequent exacerbations and to reduce activity of Chelicobacter-induced inflammation.
EFFECT: improved therapy method.
4 tbl, 2 ex
FIELD: medicine, endocrinology.
SUBSTANCE: invention relates to treatment of diabetes mellitus in mammals. Invention proposes applying inhibitors of enzyme dipeptidyl peptidase IV as an active component in manufacturing a medicinal agent, and in a method for treatment of diabetes mellitus. Invention provides enhancing the functional activity of insulin-producing cells in animal and differentiation of epithelial cells of the pancreas.
EFFECT: improved method for insulin producing and diabetes treatment.
20 cl, 5 dwg, 2 tbl, 2 ex
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to lyophilized composition comprising epotilone in the effective amount and mannitol or cyclodextrin. The second variant of the lyophilized composition involves epotilone and hydroxypropyl-beta-cyclodextrin. The preferable content of epotilone in the lyophilized composition is from 0.1% to 1.5%, and cyclodextrin - from 90% to 99% as measured for the total mass of solid components. Epotilone-containing lyophilized compositions can be used fro preparing an anti-tumor medicinal agent useful for parenteral administration and the lyophilized composition can be reduced preferably before administration directly. Epotilone-containing lyophilized compositions show improved indices of epotilone solubility and can retain stability for 24-36 months at temperature from 2°C to 30°C being without change of the solubility index.
EFFECT: improved and valuable properties of composition.
10 cl, 4 tbl, 14 ex
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, medicine, pharmacy.
SUBSTANCE: invention proposes compounds of the general formula (1): wherein X is chosen from sulfur atom and methylene group; X1 is chosen from sulfur atom and methylene group; X2 is chosen from oxygen (O), sulfur (S) atoms and methylene group; X3 means -NR5 or carbonyl group; R1 means hydrogen atom or nitrile group; R and R3 are chosen independently from hydrogen atom (H) and (C1-C6)-alkyl; R4 means R4A when X3 means -NR5 and R4B when X3 means carbonyl group; R4A is chosen from -R6R7NC(=O), -R6R7NC(=S), -R8(CH2)qC(=O), -R8(CH2)qC(=S), -R8(CH2)qSO2 and -R8(CH2)qOC(=O); R4B means -R6R7N; R5 means hydrogen atom (H); R6 and R7 are chosen independently from -R8(CH2)q, or they form in common -(CH2)2-Z1-(CH2)2- or -CHR9-X2-CH2-CHR10-; R8 is chosen from hydrogen atom (H), (C1-C4)-alkyl, cycloalkyl group condensed with benzene ring, acyl, dialkylcarbamoyl, dialkylamino-group, N-alkylpiperidyl, optionally substituted aryl, optionally substituted α-alkylbenzyl, optionally substituted aroyl, optionally substituted arylsulfonyl and optionally substituted heteroaryl representing monocyclic 5- and 6-membered ring aromatic group with one or two heteroatoms chosen from nitrogen, oxygen and sulfur atoms, and derivatives of abovementioned rings condensed with benzene; R9 and R10 are chosen independently from hydrogen atom (H), hydroxymethyl and cyanomethyl groups; Z1 is chosen from -(CH2)r-, -O-, and -N((CH2)q)R8)-; Z2 means optionally the substituted ortho-phenylene group; m = 1-3; n = 0-4; p = 2-5; q = 0-3, and r = 1 or 3. Proposed compounds are inhibitors of dipeptidyl-peptidase IV and can be used in preparing pharmaceutical compositions designated for treatment of different diseases, among them, diabetes mellitus of type 2.
EFFECT: valuable medicinal and biochemical properties of compounds and pharmaceutical composition.
22 cl, 8 tbl, 453 ex
SUBSTANCE: method involves using dipeptidyl peptidase IV (DP IV or CD 26) or DP IV-like enzyme for producing drug for treating stress or anxiety cases. Inhibitors are usable in combination with neuropeptides Y. The inhibitors are transported in physiologically compatible carriers. The inhibitors are also produced as prodrugs.
EFFECT: enhanced effectiveness of treatment.
6 cl, 11 dwg, 2 tbl
FIELD: organic chemistry.
SUBSTANCE: invention relates to new polymorphous crystalline forms of 5-[4-[2-[N-methyl-N-(2-pyridyl)-amino]-ethoxy]-benzyl]-thiazolidine-2,4-dione maleate of formula and stereomers thereof.
EFFECT: polymorphous crystalline forms of high stability.
12 cl, 1 tbl, 13 dwg, 5 ex