(57) Abstract:The proposed new tablets medicine for edema early transient incapacitation and primary reaction to radiation containing 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazole-4-one, or its hydrates, or salts thereof (ondansetron, Letran) and benzamide derivative selected from the group ArCONH2where aryl represents unsubstituted phenyl or phenyl substituted at the 3 rd position amino - or allmineral that are in a weight ratio of 1:20-500. The tool has a high activity, high reliability and easy to use. The invention relates to a new combination drug, which can be used as a means of protecting the person from the early transient incapacitation and edema of the primary reaction to radiation.Known application of 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazole-4-it, or its hydrate, or its salts (I) as a means of acute emetic response caused by the use of drugs or other means of chemotherapy and/or rentgenoterapii tumors or radiation. Most often AA (ondansetron, Letran) Patent of great Britain No. 2153821, 2290963; European patent No. 191562, 219929; the patent of Russia №1528319, 2041876, 2159614 and other Order of the chief of gumu MO of the Russian Federation No. 224 from 01.06.1996 “Of acceptance for the supply of medical services of the Armed forces of the Russian Federation tablets latrine 0,004 coated”).A disadvantage of the known medicines is the lack of latrine protection from other signs of the primary reaction to radiation and the ability to protect from early transient incapacitation.The objective of the invention is the creation of a medicinal product for human protection from early transient incapacitation and edema of the primary reaction to radiation in the form of a tablet dosage form (as is most convenient in a military context). The task is dictated by the modern methods of warfare, especially the ability to use in combat so-called tactical nuclear weapons. In these circumstances, military personnel receive significant radiation doses. Unknown to us the means of protection of the population and military personnel from the early transient incapacitation with simultaneous relief of the primary reaction to radiation. In terms of doing worrisomely such funds in the form of a pill, because these conditions dramatically reduced critical opportunities and possible panic that could lead to uncontrollable consequences.The problem is solved by creating a combo drug consisting of 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazole-4-it, or its hydrate, or its salts (1) and benzamide derivative (II) is selected from the group ArCONH2where aryl represents unsubstituted phenyl or phenyl substituted at the 3 rd position amino - or allmineral, and excipients necessary for obtaining a tablet dosage form.Most preferred is the use of 1,2,3,9-tetrahydro-9-mepl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazole-4-it is in the form of the hydrochloride dihydrate (ondansetron, latrine).As a benzamide derivative can be used benzamide, 3-aminobenzamide or acyl derivatives of 3-aminobenzamide, for example, 3-(Butylimino)benzamide.According to the invention offers the drug composition I:II=1:20-500 (weight ratio), preferably of the composition I:I=1:50-250.Since the action of irradiation or large concentrations of cm increased levels of poly (ADP-ribose), the use of inhibitors of ADP-ribosylate, in particular, the benzamide derivatives of the General formula II, is an extremely useful from the point of view of protection from these damaging factors. These qualities can be particularly useful in clinical practice in the treatment of hematological and oncological diseases. Given that the benzamide derivatives possess significant antiviral activity (EP No. 0531370, class a 61 K 31/00), the proposed remedy will be especially useful when rentgenoterapii and chemotherapy of cancer patients, when humoral immunity is significantly reduced.It is most convenient to solve the problem to use in order to themselves and others, tableted dosage form, in which in addition to the active ingredients should enter the required pharmaceutical additives and components. The required dosage form obtained by studying the compatibility of excipients with the active principles and to each other.Tablets may be made by conventional means using one or more auxiliary components. Tablets can be made using the appropriate e powder or granules, possibly mixed with a binder component, a sliding additives, inert diluent, surface-active agent or dispersing agent. Molded tablets may be coated by a shell consisting of a sugar or a special film.It is most convenient to use a tablet dosage form coated with a gastric-soluble coating. The required dosage form obtained by studying the compatibility of excipients with activetestsuite beginnings and among themselves.As auxiliary substances used calcium carbonate, kaolin, gelatin, starch, magnesium carbonate, microcrystalline cellulose, milk sugar, Aerosil and other Use as excipients microcrystalline cellulose, Aerosil and starch; the mixture of Aerosil, starch and magnesium stearate as moving and an aqueous solution of starch as a binder gave the opportunity to obtain core tablets needed to cover properties in strength. Based on hydroxypropylcellulose developed coating tablets and matched the conditions of its application.ExampleThe composition of core tablet, g:Ondansetron of gyosil 0,010Starch 0,018The stearate 0,002To cover was used colorless film-forming composition, wt.%:Oxypropylation “Klucel” 1,0Castor oil 0,4Tween-80 0,1Ethyl alcohol 96: acetone (1:1) To 100.0After coating the tablets obtained tablets are raspadaemost (102) min and release active substances to (962)%. The shelf life of the tablets is not less than 2 years. 1. Medicine for edema early passing of disability and primary reaction to radiation, including 1,2,3,9-tetrahydro-9-methyl-3-/(2-methyl-1H-imidazol-1-yl)methyl/-4H-carbazole-4-one or its hydrates or salts (I) and benzamide derivative (II) of General formula ArCONH2where AG represents unsubstituted phenyl, or phenyl substituted at the 3 rd position amino - or allmineral, at a weight ratio of I:II = 1:20-500.2. Drug under item 1, characterized in that it is a tablet dosage form.3. Drug on PP.1 and 2, characterized in that it is a tablet dosage form coated.4. Drug t in the form of the hydrochloride dihydrate.5. Drug on PP.1-4, characterized in that as the benzamide derivative (II) use benzamide, 3-aminobenzamide or 3-(Butylimino)benzamide.6. Drug on PP.1-5, characterized in that compounds I and II are used in a weight ratio of 1:50-250.7. Drug on PP.1-6, representing a tableted dosage form, in which 1,2,3,9-tetrahydro-9-methyl-3-/(2-methyl-1H-imidazol-1-yl)methyl/-4H-carbazole-4-one hydrochloride, dihydrate and benzamide are in a weight ratio of 1:50-250 and the tablet is coated with a gastric-soluble shell.
< / BR>its pharmaceutically acceptable salt and solvate, referred to as compounds of formula 1
< / BR>where R3represents (1-6C)alkyl or halogen; Q is aryl or heteroaryl, which optionally carries 1, 2, 3, or 4 substituent selected from hydroxy, halogen, cyano, nitro, amino, carboxy, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)quinil, (1-6C)alkoxy, (1-3C)alkylenedioxy, (1-6C)alkylamino and so on; R2- (1-6C)alkyl, (2-6C)alkenyl, (2-6C)quinil, (1-6C)alkoxy, (1-6C)alkylamino or di-[(1-6C)alkyl]amino; p is 0, 1 or 2; q = 0, 1, 2, 3 or 4; R4- aryl, aryl-(1-6C)alkoxy, aryloxy, arylamino, cycloalkyl or heteroaryl and R4optionally carries 1, 2, 3, or 4 substituent selected from halogen, cyano, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)quinil, (1-6C)alkoxy, (1-6C)alkylamino and so on, or its pharmaceutically acceptable salt, or cleaved in vivo ester
< / BR>where R3represents (1-6C)alkyl or halogen; m is 0, 1, 2 or 3; R1represents hydroxy, halogen, trifluoromethyl, nitro, amino, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)quinil, (1-6C)alkoxy, (1-6C)alkylamino, di-[(1-6C)alkyl] amino, amino-(2-6C)alkylamino, (1-6C)alkylamino-(2-6C)alkylamino etc
< / BR>where R3represents (1-6C) alkyl or halogen; R1selected from the substituents defined below in paragraphs (a) and (b): (A) hydroxy, halogen, trifluoromethyl, cyano, nitro, amino, carboxy, carbarnoyl, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)quinil, (1-6C)alkoxy, (1-6C)alkylamino, and so on, (C) halogen-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, carboxy-(1-6C)alkyl, (1-6C) alkoxycarbonyl-(1-6C)alkyl, and so forth, m = 1, 2, or 3; R2denotes hydroxy, halogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)quinil or (1-6C)alkoxy; p = 0 or 1; q = 0, 1, 2, 3 or 4; R4denotes aryl or cycloalkyl, where R4substituted by 1, 2 or 3 substituents selected from paragraphs (C) and (D) below: (C) is hydrogen, hydroxy, halogen, trifluoromethyl, cyano, mercapto, nitro, amino, carboxy, carbarnoyl, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)quinil, (1-6C)alkoxy, (1-6C)alkylamino, and t
FIELD: organic chemistry, pharmacology.
SUBSTANCE: invention relates to compounds of formula I ,
where R(1), R(2), R(3), R(4), R(5), R(6), R(7), R(8), R(30), and R(31) are disclosed in claims. Compound of present invention are particularly useful as new antiarrythmia bioactive substances, in particular for treatment and prophylaxis of atrial arrhythmia (e.g., atrial fibrillation or auricular flutter).
EFFECT: higher efficiency.
13 cl, 18 ex, 1 tbl
FIELD: medicine, cardiology, pharmacy.
SUBSTANCE: invention relates to pharmaceutical composition comprising atenolol as an active component and additives - starch, magnesium basic carbonate, polyvinylpyrrolidone and/or starch glycolate sodium salt, gelatin and stearate; or starch, polyvinylpyrrolidone, stearate, aerosil and microcrystalline cellulose. Composition shows improved physical-mechanical properties.
EFFECT: improved pharmaceutical properties of composition.
14 cl, 1 tbl, 5 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to derivatives of N-desacetylthiocolchicine of the formula (I):
wherein n represents a whole number from 0 to 8; Y represents group CH2 or if n = 1 then can mean group NH also. These compounds elicit an anti-proliferative activity. Also, invention describes pharmaceutical composition based on compounds of the formula (I).
EFFECT: valuable medicinal properties of derivatives.
4 cl, 1 tbl, 4 ex