Cocrystalline form of fenbufen
SUBSTANCE: claimed is a cocrystalline form of fenbufen with pyrazinamide, where molar ratio of fenbufen with pyrazinamide constitutes 1:1, which has an endothermal peak from 148 to 152°C by the data of measurements by means of differential scanning calorimetry and peaks at 2θ(°) 7.38, 10.43, 11.04, 21.67 by the data of measurement of polycrystal X-ray radiation diffraction.
EFFECT: increased rate and level of solubility of the crystalline form of fenbufen and its suitability for application in the pharmaceutical industry.
2 ex, 7 dwg
The invention relates to pharmaceutical preparations, namely to the new cocrystal of fenbufen suitable for pharmaceutical preparations.
The level of technology
γ-oxo-(1,1'-biphenyl)-4-buchanania acid, also called fenbufen,
is a well-known nonsteroidal anti-inflammatory drug used for the treatment of inflammation in osteoarthritis, ankylosing spondylitis and tendonitis [Kerwar SS Pharmacologic properties of fenbufen // Am. J. Med. - 1983 - P.62-69].
Fenbufen is a derivative of propionic acid and differs from other drugs in this group. This drug is predecessor. By itself, it is inactive, the main active metabolite is 4-biphenyloxy acid [Dhaneshwar S.S., Sharma M. Preliminary studies on gastro-protective chimeric derivative of biphenyl acetic acid for rheumatoid arthritis // Int. J. Pharm. Pharm. Sci. - 2011 - 4(1) - P.162-168]. The compound has a long half-life that allows you to apply it once or 2 times a day.
Fenbufen well absorbed in the stomach. The maximum level of the drug in plasma is reached within 1 h, and the period of its half-life in plasma is 10 hours Maximum plasma levels of the main active metabolite of fenbufen - 4-biphenylacetic acid is achieved after 7 h; the half-life of this metabolite in the plasma which is also 10 o'clock
Fenbufen subjected to intensive metabolism, products of which are excreted mainly in the urine.
Most frequent side effects are gastro-intestinal tract [Brogden R.N., R.C. Heel, Speight T.M. Avery G.S. Fenbufen: a review of its pharmacological properties and therapeutic use in rheumatic disease and acute pain // Drugs - 1981 - 21(1) - P.1-22]. The rash appears more often than in the treatment of other anti-inflammatory drugs; it can be a reason for not using this drug. Symptoms of the digestive tract (abdominal pain, nausea, vomiting, diarrhea). Also observed increased activity of hepatic enzymes, particularly with long-term use of the drug. In some cases, were recorded anemia, leukopenia, thrombocytopenia, and eosinophilia, as well as allergic reactions. Only occasionally, but were fixed erythema multiforme syndrome, Layla requiring immediate termination of the use of drugs.
It was found that fenbufen effective in rheumatoid arthritis, osteoarthritis and other chronic rheumatic diseases. Most studies were conducted before the drug 2 times a day, although for maintenance treatment was enough for a single admission. On the effectiveness of fenbufen comparable with other anti-inflammatory drugs. It felt just as easy analg tiraumea means; single dose of 600 mg was comparable with the same dose of acetylsalicylic acid; the dose of 900 mg is significantly more effective.
Therapeutic use of fenbufen and some other non-steroidal anti-inflammatory drug compounds described in the literature [Champion G.D. Therapeutic usage of the non-steroidal anti-inflammatory drugs // Med. J. Australia. - 1988 - 149(4) - P.203-213]. But no less important criteria of effectiveness of the drug are pharmacokinetic parameters and physico-chemical properties of various structural modifications such as amorphous form, salt, cocrystal, polymorphic modifications. They have different physical and chemical properties that affect pharmaceutical API parameters such as storage stability, compressibility and others. Determinants of bioavailability are solubility and kinetic indicators of dissolution. The low solubility of pharmaceutical compounds in biological fluids leads to low efficiency of the drug. Therefore, the increase of the solubility and dissolution rate of the drug is an urgent technical problem.
The problem of increasing the solubility of doing for a long time, so at the moment there are a large number of methods that solve this problem:
- fine grinding to create a larger square is square in surface dissolved compounds [J. Chaumeil .Micronisation: a method of improving the Bioavailability of poorly soluble drugs // Methods Find. Exp.Clin. Pharmcol. - 1998 - 20(3) - P.211-215],
- use of salts of the studied objects with improved solubility [S. Agharkar, Lindenbaum, S., Higuchi T. Enhancement of solubility of drug salts by hydrophilic counter-ions: properties of organic salts of an anti-malarial drug // J. Pharm. Sci. - 1976-65(5) - P.747-749],
- dissolution in the complex [Amin K., Dannenfelser, R.-M., Zielinski J., Wang B. Lyophilization of polyethylene glycol mixtures // J. Pharm. Sci. - 2004 - 93(9) - P.2244-2249] and micellar solvents [Torchillin V.. Micellar nanocarriers: pharmaceutical perspectives // Pharm. Res. - 2007 - 24(1) - P.1-16],
- the formation of supramolecular complexes with cyclodextrins [R.A. Rajewski, Stella V.J. Pharmaceutical applications of cyclodextrins. 2. In vivo drug delivery // J. Pharm. Sci. - 1996 - 85(11) - P.1142-1169],
- the use of phospholipid vesicles filled with a lipophilic compounds [Humberstone A.J., N. W. Charman Lipid-based vehicles for the oral delivery of poorly soluble drugs // Adv. Drug Deliv. Rev. - 1997 - 25(1) - P.103-128].
However, the known methods cannot be characterized as generic methods. So, despite the fact that the fine grinding of substances increases the dissolution rate of drugs, but it does not increase the equilibrium solubility of the substance. Because the increase in van der Waals interactions and electrostatic attraction between the particles lead to the reduction of effective surface area, dissolution and, thus, limit the limit of biological activity.
Increasing the solubility of the way of the receipt of unacceptable salts, as in the pharmaceutical industry are mainly used loosely of an ionisable and neutral molecules, and salt in this class of compounds not included.
The use of complex and micellar solvents suggests acceptable solubility and compatibility of molecules of medicinal compounds with the solvent, which is not always attainable.
The increase in solubility by the formation of complexes with cyclodextrins, as well as the use of phospholipid vesicles applicable only for drug compounds prolonged action, however, often require drugs fast action, for example, non-steroidal anti-inflammatory agents.
Despite the relatively high compared with other non-steroidal anti-inflammatory drug compounds solubility, fenbufen still rather poorly soluble [Chiarini, A., Tartarini, A., Fini A. pH-Solubility relationship and partitioning coefficients for some anti-inflammatory arylaliphatic acids // Arch. Pharm. - 1984 - 317 - P.268-273]. Currently work is underway, aimed at improving the solubility and/or reduction of side effects of fenbufen, such as:
- immobilization of fenbufen in nanoscale mesoporous silica [D. Carriazo, M. Del Arco, Femandez, A., Martin C., Rives V. Inclusion and release of fenbufen in mesoporous silica // J. Pharm. Sci. - 2010 - 99(8) - P.3372-3380],
- creation of complexes with cyclodextrins [I. Bratu, Gavira-Vallejo J.M., Hemanz A.1H-NMR Studyof the inclusion processes for α - and γ-cyclodextrin with fenbufen // Biopolymers - 2005 - 77 - P.361-367],
- obtaining complexes of fenbufen/poly(vinyl pyrrolidone) [Gashi Z., Censi R., Malaj L., R. Gobetto, Mozzicafreddo M., M. Angeletti, Masic, A., Di Martino P. Differences in the interaction between aryl propionic acid derivatives and poly(vinylpyrrolidone) K30: A multi-methodological approach // J. Pharm. Sci. - 2009 - 98(11) - P.4216-4228],
The creation of fenbufen immobilized in nanoscale silicon oxide, although allows to increase the kinetic characteristics of NSPs, however, does not increase the overall level of solubility. Complexes with poly(vinyl pyrrolidone) insignificant increase the solubility of fenbufen, besides the use of this method is discouraged because polyvinylpyrrolidon is harmful food additive.
It is also known that to increase the solubility by education cocrystalline form API component contributing to the increase of dissolution. Secretary is supramolecular systems, where one component is poorly soluble API, i.e. the molecule drug connection, and the second component (conformera) is the molecule soluble compounds, which are better absorbed by the body and is involved in enzymatic processes [Lara-Ochoa F. and Espinosa-Pérez G. Cocrystals definitions // Supramolecular Chemistry. - 2007 - 19 (8) - P.553-557].
Societally used in the pharmaceutical industry, are attractive because they give the possibility of obtaining new crystalline forms API with the special is Linyi properties such as improved solubility, thermal stability, improved mechanical properties, etc. moreover, due to the possibility of selection of conformer for cocrystal, you can spend, so to say, "fine tuning" of the physical properties of cocrystal.
From literature is known only one case of obtaining cocrystal of fenbufen with PP [D.J. Berry, S. Seaton, W. Clegg, R.W. Harrington, S.J. Coles, P.N. Horton, M.B. Hursthouse, R. Storey, W. Jones, T. Friscic, N. Blagden Applying hot-stage microscopy to co-crystal screening: a study of nicotinamide with seven active pharmaceutical ingredients // Cryst. Growth Des. - 2008 - 8 (5) - P.1697-1712]. However, in the present paper we do not discuss the characteristics of dissolution.
The technical problem of the invention was to find cocrystalline form of fenbufen with a higher speed and level of solubility and is suitable for use in the pharmaceutical industry.
The invention consists in the following:
Cocrystalline form of fenbufen with pyrazinamide, where the molar ratio of fenbufen with pyrazinamide is 1:1, having an endothermic peak of from 148 to 152°C as measured using differential scanning calorimetry and peaks at 2θ(°) 7.38, 10.43, 11.04, 21.67 according to the measurement dipali x-ray radiation of the polycrystal.
The claimed invention allows to obtain the following advantage - increase is astronote in water is about 25 times as compared with the solubility of fenbufen in pure form. This is important because in the presence of inflammatory processes in the human body requires effective action of the medicinal product it is in the initial period of time that is provided cocrystalline form.
Further evaluation of the kinetics of dissolution of shows on any time interval solubility cocrystalline form of fenbufen higher than compounds in pure form. Increased equilibrium solubility of fenbufen in cocrystalline form allows you to increase efficiency as prolonged drug action, and in the initial period.
Data on solubility were obtained for an aqueous solution at room temperature for installation to measure the solubility of solid compounds by the method of isothermal saturation. Samples were taken at points approximately 0.12, 0.25, 0.35, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 5, and 24 hours and analyzed using a spectrophotometer VARIAN CARY 50 UV spectral range, the operating range of wavelengths λ=190÷400 nm.
Declared a new cocrystal - solid stable crystalline substance, not falling apart, not exposed to moisture and easy to prepare stable pharmaceutical preparations. Declared cocrystal of fenbufen can be used for the production of tools for the treatment of inflammation in osteoarthritis, ankylosing who eat spondylitis and tendonitis. In addition, due to the presence of pyrazinamide received cocrystal has the ability to prevent destructive tuberculosis, caseous lymphadenitis, tuberculoma and caseous-pneumonic processes.
The structure of the claimed cocrystal proved in two ways, in the aggregate, sufficient to assert that the formation of new connections:
diffraction of x-rays of the polycrystal
differential scanning calorimetry (DSC).
Figure 1 presents a typical profile XPRD of cocrystal fenbufen:pyrazinamide (1:1) in accordance with one variant of the invention.
Figure 2 presents a typical profile XPRD of fenbufen in its purest form.
Figure 3 presents a typical profile XPRD pyrazinamide in its purest form.
Figure 4 shows a typical DSC thermogram of cocrystal fenbufen:pyrazinamide (1:1) in accordance with one variant of the invention.
Figure 5 shows a typical DSC thermogram of fenbufen in its purest form.
Figure 6 shows a typical DSC thermogram of pyrazinamide in its purest form.
Figure 7 presents data on the solubility for cocrystal fenbufen:pyrazinamide (1:1) and fenbufen in its purest form.
Information verifying the playback inventions
To get the claimed cocrystal used the following substances.
- fenbufen - producing "Sigma", CAS 36330-85-5, purity ≥98%.
- pyrazinamide - producer firm Acros Organics", lot A CAS 98-96-4, purity 99%.
- ethanol - Alcohol brand "Luxury" GOST R-2000 2001-07-01 "ethyl Alcohol requireany from food raw material. TU".
New cocrystal of fenbufen substantially characterized by the results of x-ray analysis, shown in figures 1, 2, 3, and substantially describes the data of DSC thermograms presented in figure 4, 5, 6.
To obtain the claimed cocrystal can be in solid phase and in solution.
A mixture of 51 mg (0.2 mmol) of fenbufen and 24.2 mg (0.2 mmol) of pyrazinamide placed in agate cells for grinding in the planetary micromelia. In the cell placed 10 agate beads with a diameter of 3 mm, the Process by grinding at a speed of 600 rpm continue twice for half an hour with a break of 5 minutes. The remaining powder is cocrystal fenbufen:pyrazinamide (1:1), which was confirmed by XPRD and DSC. The resulting profile XPRD final product substantially corresponds to that shown in figure 1. Received the DSC thermogram of the final product substantially corresponds to that shown in Figure 4.
A mixture of 51 mg (0.2 mmol) of fenbufen and 24.2 mg (0.2 mmol) of pyrazinamide dissolved in 2 ml of ethanol to dissolve. The obtained clear solution is left in a fume hood until olego evaporation of the solvent. The remaining powder is cocrystal fenbufen:pyrazinamide (1:1), which is confirmed by the data of DSC thermogram of which coincides with the DSC thermogram of the final product obtained according to Example 1.
Cocrystalline form of fenbufen with pyrazinamide, where the molar ratio of fenbufen with pyrazinamide is 1:1, having an endothermic peak of from 148 to 152°C as measured using differential scanning calorimetry and peaks at 2θ(°) 7.38, 10.43, 11.04, 21.67 by measuring the diffraction of x-rays of the polycrystal.
SUBSTANCE: invention relates to an organic amine salt of 6-fluoro-3-hydroxy-2-pyrazine carbonitrile, wherein the organic amine is a secondary amine, e.g., dipropyl amine, dibutyl amine, dicyclohexyl amine, dibenzylamine or N-benzylmethyl amine. The invention also relates to a method of producing said salt.
EFFECT: obtaining a novel organic amine salt of 6-fluoro-3-hydroxy-2-pyrazine carbonitrile having excellent crystallinity and which is suitable as an intermediate compound for producing 6-fluoro-3-hydroxy-2-pyrazine carboxamide.
6 cl, 1 tbl, 5 ex
SUBSTANCE: invention relates to a compound of formula I:
, where A denotes CH or N; R1 is selected from a group consisting of: cycloalkyl which is unsubstituted or substituted with hydroxy, lower hydroxyalkyl or lower alkoxy, 1-hydroxy-2-indanyl, lower hydroxyalkyl, lower hydroxy haloalkyl, lower hydroxy alkoxyalkyl, CH2-CR9R10-cycloalkyl and -CR11R12- COOR13; R9 denotes hydrogen or lower alkyl; R10 denotes hydrogen, hydroxy or lower alkoxy; R11 and R12 independently denote hydrogen or lower alkyl; R13 denotes lower alkyl; R2 denotes hydrogen; or R1 and R2 together with the nitrogen atom with which they are bonded form a morpholinyl ring; R15 is selected from a group consisting of lower alkoxyalkyl, cycloalkyl and furanyl, substituted with halogen; R17 is selected from a group consisting of hydrogen, lower alkyl and lower haloalkyl; R4 and R8 independently denote hydrogen or halogen; R5 and R7 are independently selected from a group consisting of hydrogen, lower alkyl, lower alkoxy, halogen, lower haloalkyl, lower haloalkoxy and cyano; R6 is selected from a group consisting of hydrogen, lower alkoxy, halogen, lower haloalkyl, lower haloalkoxy and cyano; and pharmaceutically acceptable salts thereof. The invention also relates to use of said compounds to produce medicinal agents for treating and/or preventing diseases which can be cured by HDL-cholesterol raising agents and to a pharmaceutical composition based on said compounds.
EFFECT: novel compounds which can be useful in treating diseases which can be treated with HDL-cholesterol raising agents are obtained and described.
36 cl, 164 ex
SUBSTANCE: invention relates to compounds of formula where R1 denotes C1-C6alkyl; W denotes pyrazolyl, triazolyl or imidazolyl; R14 denotes phenyl or a 6-member heteroaromatic ring containing 1-3 nitrogen ring atoms, which is may be substituted with at least one substitute selected from F, Cl, CN and CF3; R3 denotes phenyl, substituted with a trifluoromethyl substitute; R4 denotes hydrogen or C1-C6alkyl; X denotes -C1-C6alkylene-Y-, and Y denotes a single bond, and the alkylene group is a straight or branched C1-C6alkylene, possibly substituted with OH, CO2R66 or C1-C3alkoxy; R5 denotes phenyl or pyridinyl, substituted with -S(O)vR21; or R5 denotes an unsubstituted C3-C6cycloalkyl ring; or R5 can also denote H; R21 denotes hydrogen, C1-C6alkyl or C3-C8cycloalkyl; v equals 1 or 2; and R66 denotes hydrogen or C1-C6alkyl; or pharmaceutically acceptable salts thereof. The invention also relates to a method of producing said compounds, intermediate compounds and a pharmaceutical composition for treating or reducing the risk of disease or condition, in which inhibiting neutrophil elastase activity based on compounds of formula (I) is useful.
EFFECT: obtaining novel compounds which can be used in medicine to treat or reduce the risk of disease or condition in which inhibiting neutrophil elastase activity is useful.
19 cl, 16 ex
SUBSTANCE: present invention refers to the compound 5-[3-[(2S)-1-(difluoromethoxy)-propane-2-yl]-oxy-5-[(5-methylpyrazin-2-yl)-carbamoyl]]phenoxy]-N,N-dimethyl-pyrazine-2-carboxamide. The invention also refers to a pharmaceutical composition, and also to application of the compound under cl.1.
EFFECT: making the new biologically active compounds showing GLK (glucokinase) activator activity.
5 cl, 6 ex, 2 tbl, 2 dwg
SUBSTANCE: described are novel compounds of general formula
:, where X denotes halogen or (C1-C3)alkyl possibly substituted with a halogen; Y denotes hydrogen; R denotes hydrogen, halogen, cyano, (C1-C6)alkyl or (C2-C6)alkenyl possibly substituted with a halogen, (C2-C6)alkynyl possibly substituted with a halogen or hydroxy, (C1 -C6)alkoxy or (C2-C6)alkenyloxy, possibly substituted with a halogen, (C1-C6)alkoxycarbonyl, (C1-C6)alkoxyamino(C1-C3)alkyl, phenyl, phenoxy, pyridyloxy or pyrimidyloxy, possibly substituted; n is an integer from 1 to 5; a plant disease control agent and a plant disease control method.
EFFECT: obtaining compounds with a wider suppressing spectrum at low doses of chemical processing, thus facilitating use as a plant disease control agent for agricultural and horticultural use, as well as reduced harmful effect on the environment.
4 cl, 6 tbl, 10 ex
SUBSTANCE: described is 2-alkyl-cycloalk(en)yl-carboxamides of formula
, in which X, s, R1 , L, R2 and A assume values given in the formula of invention, a method of producing said compounds, an agent and use of said compounds against unwanted microorganisms.
EFFECT: higher activity compared to existing compounds, low toxicity and high toleration by plants.
6 cl, 8 tbl, 6 ex
SUBSTANCE: present invention relates to hot or sweet flavourants in form of a synthetic amide compound or edible salt thereof in amount ranging from approximately 0.001 parts per million to approximately 100 parts per million. The amide compound has formula
where A is a phenyl or a 5- or 6-member heteroaryl ring selected from a group comprising pyridine, pyrazine, pyrazole, thiazole, furan, thiophene, benzofuran and benzothiophene; m equals 1, 2 or 3, each R1 is independently selected from hydroxyl, fluorine, chlorine, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy and isopropoxy, or alternatively two R1 are bonded to form a saturated C1-C3 alkylenedioxy ring on the phenyl; and R2 is a C3-C10 branched alkyl. The amide compound also has formula
in which substitutes A, B, R50, R60, R70, R80, n and m assume values given in the formula of invention. The amide compound is also a specific chemical compound.
EFFECT: obtaining hot and sweet taste modifiers and boosters for food and medicinal products.
39 cl, 7 tbl, 180 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to compound of formula 2: and to its pharmaceutically acceptable salts and their mixtures, where values of R, M, Q, Z, W, D radicals are described in i.1 of the invention formula. Invention also relates to pharmaceutical compositions, which possess inhibiting activity with respect to Btk, based on formula 2 compounds.
EFFECT: obtained are novel compounds and based on them pharmaceutical compositions which can be applied in medicine for treatment of patients with diseases associated with inhibiting Btk activity and/or B-cell activity.
55 cl, 19 ex
FIELD: chemistry, pharmacology.
SUBSTANCE: invention relates to novel compounds -acidified arylcycloalkylamins of formula I in any of their stereoisomeric forms or in form of their mixture in any ratio, or their pharmaceutically acceptable salts, where in formula I : R1 represents aryl, not obligatory substituted with one or two similar or different substitutes, selected from group that includes C1-C6-alkyl and halogen; R2 represents aryl or heteroaryl, which represents residue of 5-6-member aromatic monocyclic heterocycle, containing 1-2 nitrogen atoms as heteroatom and/or 1 sulfur atom or oxygen atom, or residue of 9-10-member aromatic bicyclic heterocycle, containing 1-2 nitrogen atoms as heteroatom, each of which is unsubstituted or contains 1-3 similar or different substitutes, selected from group, consisting of halogens, NH2, unsubstituted C1-C10-alkyl, C1-C10 -alcoxy, C1-C10-alkylamino and di(C1-C10-alkyl)amino, and at least monosubstituted C1-C10-alkyl, etc., n represents 1, 2, 3 or 4. Invention relates to pharmaceutical composition, stimulating expression of endothelial NO synthase, based on said compounds, as well as application of compounds of formula I for production of medication for stimulating expression of endothelial NO-synthase and for treatment of such cardiovascular diseases as atherosclerosis, thrombosis, coronary artery disease, hypertension and impaired cardiac function.
EFFECT: invention ensures enhancing composition and treatment method efficiency.
9 cl, 2 tbl, 41 ex
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to new acid-additive nitrate salts of compounds taken among salbutamol, cetirizine, loratidine, terfenadine, emedastine, ketotifen, nedocromil, ambroxol, dextrometorphan, dextrorphan, isoniazide, erythromycin and pyrazinamide. Indicated salts can be used for treatment of pathology of respiratory system and elicit an anti-allergic, anti-asthmatic effect and can be used in ophthalmology also. Indicated salts have less adverse effect on cardiovascular and/or gastroenteric systems as compared with their non-salt analogues. Also, invention proposes pharmaceutical compositions for preparing medicinal agents for treatment of pathology of respiratory system and comprising above indicated salts or nitrate salts of metronidazol or aciclovir.
EFFECT: improved and valuable properties of compounds.
6 cl, 5 tbl, 19 ex
FIELD: organic chemistry.
SUBSTANCE: invention relates to new method for production of m- or p-substituted α-arylalkanecarboxylic acids of general formula I
from respective α-hydroxylated derivatives using inexpensive reagents and without converting of any reducible groups such as ester or ketone ones in side chains. In formula R is hydrogen, C1-C6-alkyl; R1 is hydrogen, linear or branched C1-C6-alkyl, phenyl, p-nitrophenyl, alkali or earth-alkali cation or cation of pharmaceutically acceptable ammonia salt: A is C1-C4-alkyl, aryl, optionally substituted with one or more alkyl, hydroxy, etc., aryloxy, arylcarbonyl; A is in m- or p-sites; P - linear or branched C1-C6-flkyl, phenyl, nitrophenyl. Claimed method includes the next steps: a) converting of compounds of formula II to compound of formula III either by reaction of II with compound of formula in presence of organic or inorganic base or by reaction of II with thiophene of formula and followed by reaction of obtained product with HNRaRb, wherein Ra andRb are as defined above; b) thermal rearrangement of III to form IIIb ; c) catalytic dehydration of IIIb to form IIIc ; and d) optional hydrolysis of IIIc to obtain target compound of formula I. Also are disclosed new compounds of formulae III and IIIb.
EFFECT: new α-arylalkanecarboxylic acids and intermediates thereof.
6 cl, 5 ex
SUBSTANCE: with underlying antituberculous therapy from the first day of treatment, a therapeutic course is added with an oral administration of preparations Wobenzym and Thiotriazoline; Wobenzym is administered for 4 months in a dose of 1 tablet once a day 30 minutes before breakfast, while Thiotriazoline is administered for the first 15 days in a dose of 100 mg 2 times a day, from the 16th to 45th day in a dose of 100 mg 1 time a day, on the 46th day, Thiotriazoline is withdrawn.
EFFECT: method enables higher clinical effectiveness and reduced rate of an adverse hepatotoxic response to the antituberculous preparations due to improving the immune status and peroxidation values.
6 tbl, 2 ex
SUBSTANCE: rifabutin is dissolved in a water-miscible solvent which dissolves rifabutin better than water does; a rifabutin solution is prepared; gelatin is dissolved in water to prepare a gelatin solution; the rifabutin solution is slowly added to the gelatin solution while stirring to prepare a semi-product. The semi-product is dried in a spray drier or lyophilised to prepare a product. The prepared product is used as a part of a pharmaceutical composition for treating mycobacteriosis and Helicobacter pylori infection.
EFFECT: higher bioavailability of rifabutin.
46 cl, 8 tbl, 5 ex, 7 dwg
SUBSTANCE: invention represents 3-aminosubstituted 6-(3,5-dimethylpyrazol-1-yl)-1,2,4,5-tetrazines, which applied as anti-tuberculosis medications make it possible to increase activity and specificity of antimicrobacterial action, extend its spectrum (impact on atypical strains of mycobacteria) as well as reduce toxicity in comparison with analogues.
EFFECT: toxicity of claimed compounds is 10-20 times lower than toxicity of anti-tuberculosis medications applied in medicine.
5 tbl, 16 ex
SUBSTANCE: in an intensive phase of the therapeutic course, a conventional anti-tuberculosis therapy is added with the oral preparation Thiotriazoline 100 mg 2 times a day daily for 45 days. Besides, pulmonary administration of the preparation Hixozide 350 mg dissolved in 10 ml of water for injection every second day in the number of 20 procedures is added.
EFFECT: infiltrate resolution, cavity closure and abacillation with no hepatotoxic reaction ensured by creating high concentrations of drug preparations directly in the lesion and increased activity of the immune system.
2 ex, 3 tbl
SUBSTANCE: invention refers to a number of bicyclic nitroimidazole-replaced phenyloxazolydinones of the following structural formula (I):
containing nitroimidazole circle, or to its pharmaceutically acceptable salt; where R1 represents hydrogen, (C1-C6)alkyl or aryl; n is equal to 0, 1 or 2; X1 and X2 independently represent H, CF3, CI, OCF3 or F; G represents -OH, triazole or -NHCOR2; R2 represents (C1-C6)alkyl, cycloalkyl or aryl; and L represents a bond or a linker group chosen from any combination 2-3 of the following groups: 1) (C1-C6)alkylene, 2) (C3-C8)cycloalkylene, 3) arylene, arylene-replaced CN, ore arylene-replaced F, 4) group chosen from the group consisting of
where R10 represents H, CF3, hydroxyl, amino, alkyl, alkylamino, alkoxy or aryl, and R13 represents H, hydroxyl, amino, alkyl, alkyl amino, alkoxy or aryl, or R13 in combination with nitroimidazole circle can form spiral-shaped structure, 5) -C(=O)-, 6) -O-, 7) -S(O)n-, in which n is equal to 0.1 or 2, 8) -N(R3)-, 9) -C(R4)=C(R5)-, R3 represents hydrogen, (C1-C6) alkyl or aryl, and R4 and R5 represent hydrogen, (C1-C6) alkyl or aryl, or R4 and R5 can be combined together so that they can form a bond. Besides, the invention refers to pharmaceutical composition for treatment of bacterial infection based on compounds of formula I, as well as to a bacterial infection treatment method.
EFFECT: invention describes new compounds that have antibacterial activity against a line of wild type and stable lines of pathogenic microorganisms, and as a result, are suitable for prevention, control and treatment of a number of human and mammal bacterial infections caused by these pathogenic microorganisms such as bacillus Kochii.
15 cl, 93 ex, 1 tbl, 22 dwg