Combination of cytochrome-p450-dependent protease inhibitors

FIELD: medicine.

SUBSTANCE: invention refers to medical products and concerns combination for HIV-infection treatment, containing (a) therapeutically effective amount of HIV-protease inhibitor by formula or its pharmaceutically accepted salt or ester and (b) effective amount of rhytonavir or its pharmaceutically accepted salt or ester. Besides, method of improved pharmacokinetics of HIV-protease inhibitor by formula (4) or its pharmaceutically accepted salt or ester, including introduction to an individual requiring such treatment, therapeutically effective amount of rhytonavir or its pharmaceutically accepted salt or ester with therapeutically effective amount of specified HIV-protease inhibitor by formula (4) is described.

EFFECT: offered combination has synergetic action if taken in any molar ratios.

33 cl, 6 dwg, 9 tbl, 4 ex

 

The text descriptions are given in facsimile form.

1. Combination for the treatment of HIV infection containing (a) a therapeutically effective amount of an inhibitor of HIV protease formula (4)

or its pharmaceutically acceptable salt or a complex ester and (b) an effective amount of ritonavir or its pharmaceutically acceptable salt or a complex ester.

2. The combination according to claim 1, in which the components contained in the specified combination, you can enter together or separately.

3. The combination according to claim 1, where the mass ratio of the inhibitor of HIV protease formula (4) to ritonavir is in the range from 40:1 to 1:15.

4. The combination according to claim 1, where the mass ratio of the inhibitor of HIV protease formula (4) to ritonavir is in the range from 30:1 to 1:15.

5. The combination according to claim 1, where the mass ratio of the inhibitor of HIV protease formula (4) to ritonavir is in the range from 10:1 to 1:10.

6. The combination according to claim 1, where the mass ratio of the inhibitor of HIV protease formula (4) to ritonavir is in the range from 8:1 to 1:8.

7. The combination according to claim 1, where the mass ratio of the inhibitor of HIV protease formula (4) to ritonavir is in the range from 6:1 to 1:6.

8. The combination according to claim 1, where the amount by weight of the inhibitor of HIV protease formula (4) is equal to or greater than the number of ritonavir.

9. The combination according to claim 1, where the mass ratio of the inhibitor of HIV protease formula (4) to ritonavir is in the range from 1:1 to 15:1.

10. The combination according to claim 1, where the mass ratio of the inhibitor of HIV protease formula (4) R is canavero is in the range from 1:1 to 8:1.

11. The combination according to claim 1, where the mass ratio of the inhibitor of HIV protease formula (4) to ritonavir is in the range from 1:1 to 6:1.

12. The combination according to claim 2, in which the components contained in the specified combination, are administered together twice a day, and the amount of the compounds of formula (4) at a dose of from 50 to 1500 mg, and the amount of ritonavir per dose ranges from 50 to 1500 mg

13. The combination indicated in paragraph 12, in which the amount of the compounds of formula (4) at a dose of from 100 to 1000 mg and the amount of ritonavir at a dose of from 100 to 800 mg

14. The combination indicated in paragraph 12, in which the amount of the compounds of formula (4) at a dose of from 150 to 800 mg, and the amount of ritonavir at a dose of from 100 to 600 mg

15. The combination indicated in paragraph 12, in which the amount of the compounds of formula (4) at a dose of from 200 to 600 mg and the amount of ritonavir at a dose of from 20 to 300 mg

16. The combination according to claim 2, in which the components contained in the combination are administered together twice a day, and the amount of the compounds of formula (4) at a dose of 600 mg and the amount of ritonavir at a dose of 100 mg.

17. The combination according to claim 2, in which the components contained in the combination are administered together once a day, and the amount of the compounds of formula (4) at a dose of from 50 to 1500 mg, and the amount of ritonavir at a dose of 50 is about 1500 mg.

18. The combination of 17, in which the amount of the compounds of formula (4) at a dose of from 100 to 1000 mg and the amount of ritonavir at a dose of from 100 to 800 mg

19. The combination of 17, in which the amount of the compounds of formula (4) at a dose of from 150 to 800 mg, and the amount of ritonavir at a dose of from 100 to 600 mg

20. The combination of 17, in which the amount of the compounds of formula (4) at a dose of from 200 to 600 mg and the amount of ritonavir at a dose of from 20 to 200 mg.

21. Pharmaceutical composition suitable for the treatment of HIV infection, containing (a) an inhibitor of HIV protease formula (4)

or its pharmaceutically acceptable salt or ester in therapeutically effective amount, (b) ritonavir or its pharmaceutically acceptable salt or ester in an effective amount and (C) pharmaceutically acceptable excipient.

22. Set containing (a) a pharmaceutical composition comprising a therapeutic amount of an inhibitor of HIV protease formula (4)

or its pharmaceutically acceptable salt or ester, and (b) ritonavir or its pharmaceutically acceptable salt or ester, for simultaneous, separate or sequential use in the treatment of HIV infection.

23. The combination of lubomia claims 1 to 20 for use in the treatment of HIV infection.

24. The use of a combination according to any one of claims 1 to 20 in the manufacture of drugs to treat HIV infection.

25. The use of a combination according to any one of claims 1 to 20 in the manufacture of pharmaceuticals for inhibition of the protease of human immunodeficiency virus (HIV) in a mammal infected with the indicated HIV.

26. The use of a combination according to any one of claims 1 to 20 in the manufacture of a medicine for inhibiting replication of human immunodeficiency virus (HIV).

27. The application of paragraph 24, where the human immunodeficiency virus (HIV) is an HIV resistant to many drugs.

28. The use of ritonavir or its pharmaceutically acceptable salt or its complex ester in combination with the compound of the formula (4)

or its pharmaceutically acceptable salt or its complex with ether to improve the pharmacokinetics of the compounds of formula (4) with respect to pharmacokinetics in the case where the compound of formula (4) to impose one, in the manufacture of pharmaceuticals for inhibition of viral proteases.

29. The use of ritonavir or its pharmaceutically acceptable salt or its complex ester in combination with the compound of the formula (4)

or its pharmaceutically acceptable salt or its complex is firm in the manufacture of a medicinal product for treating or preventing a person with HIV infection, characterized in that the specified combination is suitable for improving the pharmacokinetic variables of the compounds of formula (4) with respect to pharmacokinetic variables in the case when the compound of the formula (4) to impose one.

30. Applying a combination of on clause 29, where the number of ritonavir is sufficient to improve at least one of the pharmacokinetic variables selected from CminCmaxAUC for 12 h, the relative pharmacokinetic variables in the case when the compound of the formula (4) to impose one.

31. Applying a combination of on clause 29, where the number of ritonavir is sufficient to improve at least one of the pharmacokinetic variables of the compounds of formula (4)selected from CminWithmaxCss,avAUC for 12 h (AUC) for 24 h, relative to the pharmacokinetic variables in the case when the compound of the formula (4) to impose one.

32. Method for improving the pharmacokinetics of an inhibitor of HIV protease formula (4)

or its pharmaceutically acceptable salt or a complex ester, comprising the administration to an individual in need of such treatment, a therapeutically effective amount of ritonavir or its pharmaceutically acceptable salt or its complex ester with a therapeutically effective amount of the indicated inhibitor of HIV about what easy formula (4).

33. A method of treating HIV infection comprising the administration to a patient in need of such treatment, a therapeutically effective amount of the compounds of formula (4)

or its pharmaceutically acceptable salt or its complex ester with a therapeutically effective amount of ritonavir or its pharmaceutically acceptable salt or a complex ester.



 

Same patents:

FIELD: medicine; pharmacology.

SUBSTANCE: invention refers to new compounds of and formula: I II those developing antiviral activity allowing application in pharmaceutical formulations and for antiviral medicines production.

EFFECT: new compounds have useful biological properties.

5 cl, 3 dwg, 6 tbl, 3 ex

FIELD: medicine, molecular biology, antibodies.

SUBSTANCE: invention relates to an antibody raised against CCR5 and comprising: (i) two light chains wherein each light chain comprises product of plasmid expression and designated as pVK:HuPRO140-VK (ATCC - PTA-4097), and (ii) two heavy chains wherein each heavy chain comprises product of plasmid expression and designated as pVg4:HuPRO140 HG2-VH (ATCC - PTA-4098), or plasmid designated as pVg4:HuPRO140 (mut B+D+I)-VH (ATCC - PTA-4099), or fragment of such antibody binding with CCR5 on a human cell surface. Invention relates to nucleic acid encoding light and heavy chains of antibody, expression vector, cell-host transformed with at least one vector, and a method for preparing antibody. Antibody is used as an active component in composition used for inhibition of infection of cells CD4 + HIV-1, and to a pharmaceutical composition used in treatment of a patient with HIV-1 infection. Also, invention relates to antibody conjugate against CCR5 and its using. Use of antibodies provides enhancing effectiveness of prophylaxis and treatment of HIV-1 infection.

EFFECT: valuable medicinal properties of antibody.

31 cl, 23 dwg, 3 ex

FIELD: organic chemistry, medicine, virology.

SUBSTANCE: invention relates to novel 5'-phosphonates of 3`-azido-3`-deoxythymidine of the general formula (I) possessing anti-HIV activity, and to using 5'-phosphonates of 3`-azido-3`-deoxythymidine as an active component for preparing drugs possessing anti-HIV activity. In compound of the general formula (I): at n = 0-2; R1 means (wherein X means -CH2, -NH, O); R2 means -NH-C(O)- (wherein R2 means H, (C1-C6)-alkyl, (C5-C7)-cycloalkyl), -HO(CH2)k- (wherein k = 2-4); at n = 0 R1 means -Cl3C; at n = 1-6 R1 means Cl-, Br-, J-, and at n = 2-6 R3 means -C(O)O- (wherein R3 means (C1-C6)-alkyl) at n = 2-6.

EFFECT: valuable medicinal properties of compounds.

3 cl, 2 tbl, 10 ex

FIELD: medicine, pharmacology, pharmacy.

SUBSTANCE: pharmaceutical composition comprises abacavir and alovudin taken in the ratio = (1-10):(200-800) and a pharmaceutical carrier for them. Package designated for a patient for treatment of poly resistant HIV comprises alovudin and abacavir and information instruction for using both alovudin and abacavir in combination. Use of abacavir in common with alovudin for treatment of polyresistant HIV wherein use involves simultaneous, combined or successive administration of alovudin and abacavir. Invention provides more inhibition of virus, suppression of virus for longer period, limiting safety for arising mutations and development of polyresistant HIV, and decreasing toxicity of drugs.

EFFECT: valuable properties and enhanced effectiveness of drugs.

10 cl, 1 tbl, 3 dwg, 2 ex

FIELD: medicine, polymers.

SUBSTANCE: invention relates to conjugates consisting of a water-soluble polymer of molecular mass from 200 to 20000 Da and representing polyethylene glycol or alkyl chain to which two molecules of synthetic peptides, not less, are bound by reactive functional group and wherein each peptide comprises amino acid sequence originating from region HR1 or HR2 of human immunodeficiency virus (HIV) gp41. Invention relates to methods for using these conjugates for delivery inhibition of to HIV target-cell by addition of indicated conjugates in the amount providing effective inhibition of cell infection with indicated virus. Also, invention relates to methods for preparing conjugates by functional adding of each molecule of synthetic peptide to polymer through reactive functional group.

EFFECT: valuable biological properties of conjugates.

27 cl, 2 dwg, 6 tbl, 6 ex

FIELD: organic chemistry of natural compounds.

SUBSTANCE: invention relates to novel compounds, namely, to N'-{N-[3-oxo-lupan-28-oyl]-9-aminononanoyl}-3-amino-3-phenylpropionic acid and its salts of the formula (I) given in the invention description. This compound shows antiviral activity, in particular, anti-HIV activity, and immunostimulating activity. Compounds of the formula (I) are nontoxic and can be obtained from betulin isolated from birch bark as available raw with the high yield.

EFFECT: valuable medicinal properties of compound.

4 tbl, 9 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of piperidine of the general formula (I): or their pharmaceutically acceptable salts or isomers wherein Q means nitrogen atom (N); X and Z are chosen independently from group consisting of -CH and N under condition that one or both groups among Q and Z mean N; R, R4, R5, R and R are chosen independently from group consisting of hydrogen atom (H) and (C1-C6)-alkyl; R1 means H, (C1-C6)-alkyl, R9-aryl-(C1-C6)-alkyl-, (C1-C6)-alkyl-SO2-, (C3-C6)-cycloalkyl-SO2-, fluoro-(C1-C6)-alkyl-SO2-, R9-aryl-SO2-, R9-heteroaryl-SO2-, -N(R22)(R23)-SO2-, (C1-C6)-alkyl-C(O)-, (C3-C6)-cycloalkyl-C(O)-, fluoro-(C1-C6)-alkyl-C(O)-, R9-aryl-C(O)-, CH3CH2-NH-C(O)- or R9-aryl-NH-C(O)-; R2 means H or (C1-C6)-alkyl, and R3 means H, (C1-C6)-alkyl, (C1-C6)-alkoxy-(C1-C6)-alkyl-, (C3-C10)-cycloalkyl-, (C3-C10)-cycloalkyl-(C1-C6)-alkyl-, R9-aryl, R9-aryl-(C1-C6)-alkyl- or R9-heteroaryl under condition that each X and X doesn't mean N, or R2 and R3 in common mean =NOR10. Proposed compounds can be used as selective CCR5 antagonists. Compounds are useful in HIV treatment. Also, invention describes a pharmaceutical composition based on compounds thereof and combination with antiviral or anti-inflammatory agent.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

16 cl, 4 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: invention relates to method for reducing of LDL-cholesterol and/or triglyceride level increased due to therapy by HIV protease inhibitors in HIV-infected subjects. According to invention Atazanavir is administered in combination with other HIV protease inhibitor, metabolized cytochrom P450 monooxygenase in therapeutically effective amounts.

EFFECT: effective treatment due to Atazanavir ability to cytochrom P450 monooxygenase inhibition; increased concentration of HIV protease inhibitors without preparation dose.

3 cl

FIELD: medicine, biology, virology.

SUBSTANCE: invention involves creature of complex of membranotropic compounds providing target delivery of antiviral preparation to HIV-1/2 damaged focus and suppression of viral infection at initial and later steps of its development. Invention provides effect on more expanded targets of human immunodeficiency virus and blocking HIV-infection at the early steps of interaction virus/cell based on synergism of components in the proposed complex. Modifying agents of polyanionic matrix - norbornene or adamantine and peptide-simulators of HIV-1/2 co-receptor bind with different sites of gp120 of HIV-1 that excludes the competition possibility and reciprocal steric hindering in virus-specific pharmacophore-modifying agents. Invention can be used for prophylaxis of HIV-infection and AIDS treatment, and in research works for study of ligand-receptor interaction (of type surface viral proteins - cellular receptors).

EFFECT: valuable biological and medicinal properties of complex.

3 cl, 5 tbl, 2 dwg, 3 ex

FIELD: chemistry of peptides, virology.

SUBSTANCE: invention relates to novel chemical compounds, namely, to glycyrrhizic acid (GA) glycopeptide with glycyl-L-phenylalanine: 3-O-{2-O-[N-(β-D-glucopyranosyluronoyl)-glycyl-L-phenylalanine-N-(β-D-glucopyranosyluronoyl)-glycyl-L-phenylalanine)]}-(3β,20β)-11-oxo-olean-12-ene-30-oic acid possessing anti-HIV-1 activity. This compound shows less toxicity (CD50 = 250 mcg/ml) as compared with the known anti-HIV preparation azidothymidine (CD50 = 3.5 mcM) and elicits the expressed anti-HIV-1 activity of high effectiveness and inhibits accumulation of virus-specific protein p24 (ID50 = 0.73 mcg/ml) that by 170-fold lower as compared with GA. This compound exceeds GA by the selectivity index (IS = 342.5) by 30-fold in culture cells MT-4 infected with the strain HIV-1/EVK. Glycopeptide in the concentration 0.80 mcg/ml (ID90 = 0.80 mcg/ml) inhibits reproduction of virus by 90%. Anti-HIV-1 activity (inhibition of p24) of the proposed compound in the concentration 10 mcg/ml is similar with activity of azidothymidine in the dose 0.05 mcg/ml.

EFFECT: enhanced and valuable antiviral properties of compound.

3 tbl, 2 ex

FIELD: bioengineering.

SUBSTANCE: novel polynucleotide is invented which is produced from the nucleotide sequence of the IFNα-17 gene, containing the single nucleotide polymorphism SNP g771c. Also, the novel polynucleotide is invented which is derived from the natural protein IFNα-17 of the wild type containing SNP G45R.

EFFECT: can be used for producing effective therapeutic agent with antiviral, antiproliferative and/or immunomodulating activity.

13 cl, 5 dwg, 6 ex

FIELD: medicine; pharmacology.

SUBSTANCE: invention refers to creation and application of aerosol spray compositions for treatment of diseases or disorders requiring lowering of cell proliferation and/or induction of cell apoptosis, such as neoplastic, autoimmune, viral diseases. Agent contains as active substance vitamin E based composition of structural formula , where R1 is carboxylic acid; R2 and R3 are hydrogen or R4; R4 is methyl, and R5 is alkyl; or where R1 is hydrogen or carboxylic acid; R2 and R3 are hydrogen or R4; R4 is methyl, and R5 is alkenyl.

EFFECT: improved delivery of specified composition by inhalation with intensified antiproliferation activity.

59 cl, 17 dwg, 6 tbl, 35 ex

FIELD: medicine.

SUBSTANCE: method of production of dry polyvalent virus-vaccine includes separate infection of cell culture with strain PC-126 of turkey herpesvirus (virus of Marek's disease 3rd serotype) and one-day chicken infected with chicken herpesvirus (virus of Marek's disease 2nd serotype), incubation, turkey herpesvirus harvest, and sampling of double flag follicles of chicken herpesvirus infected chicken, protective medium addition, separate ultrasonic processing of virus cell mass and flag follicle mass, freezing and drying of end product followed with their mixing. At that chicken herpesvirus strain are sampled for (VMD 2nd serotype) strains "42", "50", "SB-1", inoculated in dosage 10000-50000 functional residual capacity (FRC) for chicken and grown in body within 12-25 days. Follicles processed with ultrasonic is removes, and protective medium processed with ultrasonic and containing released chicken herpesvirus is added equal proportion of processed with ultrasonic clean cell cultures of bird embryos grown within 24-72 hours. Dry polyvalent virus-vaccine contains cell-free lyophilized strain FC-126 of turkey herpesvirus - 3rd serotype of Marek's disease virus in protective medium. In addition virus-vaccine includes cell-free lyophilised strains of chicken herpesvirus - 2nd serotype of Marek's disease virus, produced by any cl.1-5, in protective medium at ratio 2000 FRC /units: 100-5 00 FRC /units, respectively.

EFFECT: vaccine has high immunogenic activity and storage stability.

10 cl, 3 tbl, 4 ex

Poplar-aspen oil // 2326685

FIELD: medicine; pharmacology.

SUBSTANCE: agent contains oil extract of poplar buds and sprouts and oil extract of aspen buds and sprouts with component ratio as follows, mass.%: oil extract of poplar buds and sprouts 20-90, oil extract of aspen buds and sprouts 10-80, mixed oil extract of poplar buds and sprouts and oil extract of aspen buds and sprouts, with component ratio as follows, mass.%: oil extract of poplar buds and sprouts 20-90, oil extract of aspen buds and sprouts 10-80, as well as fat extract of plant raw with plant component ratio as follows, mass.: marsh tea 3, comfrey 3, blueash 2, silver fir 1, common burdock (root) 2, horseheal (root) 1, deer's-tongue 1, horseradish 1, musquash-poison 2, hog bean (herb) 2, hop (cones) 2, cowberry (root) 2, mountain arnica (blossom) 2, ratio of oil extracts and fat extract of plant raw is 1:3 respectively.

EFFECT: agent allows widening range of preventive and therapeutic herbal medicinal agents of antiviral and anti-inflammatory action.

2 cl, 9 ex

FIELD: veterinary; veterinarian virology.

SUBSTANCE: production of dry cultural rinderpest virus-vaccine for minor ruminants includes growing of virus containing raw materials from "45G37/35-K" rinderpest virus strain in cell culture, introduction of protective medium and production of the end product. Passaged cell culture of saiga kidney is used as a cell culture. Infected culture is incubated under roller conditions during 5-7 days with the change of supporting medium each 2-3 days. Virus containing culture is mixed before freeze drying in proportion 1:1, and then freeze dried until moisture mass fraction is no more than 4%. Finally, it is packed into ampoules. The end product contains virus raw materials, peptone, sucrose, gelatine and demineralised water.

EFFECT: high-performance production of standard and innocuous rinderpest virus-vaccine for minor ruminants stable for storage conditions.

2 cl, 3 ex

FIELD: medicine, pharmacology.

SUBSTANCE: mixture of chitosonium glutamate obtained from high molecular chitosan with molecular mass 100-500 kD, and restrictedly depolymerised low polymeric chitosan with molecular mass 0.5-20 kD, is added to the inactivated flue vaccine as an adjuvant; the molecules of chitosan and chitosonium glutamate have free aldehydic groups at one of their free end, and have the deacetylation degree within 60-90%; the concentration of high molecular chitosan is brought to 0.5%, and low polymeric chitosan - to 0.05%, and the parenteral vaccination is performed.

EFFECT: method increases the immunogenicity of inactivated flue accine.

4 dwg, 4 ex

FIELD: medicine, veterinary.

SUBSTANCE: vaccine contains active substance and food additive. Active substance consists of efficient amount of avirulent antigenic material from "Novosibirsky" bird flue strain Influenzae virus avicum, Orthomyxoviridae family, serotype A, subtype H5N1, collection of FGU "VGNKI" VNIISZH N. 125 - deposition "Novosibirsky".

EFFECT: vaccine provides the efficient bird protection against the epizootic virus and prevents the environmental propagation of infectious agent from immunized bird.

6 cl, 12 tbl, 7 ex

FIELD: organic chemistry, medicine, pharmacy, chemical technology.

SUBSTANCE: invention relates to novel substituted esters of 1,2,3,7-tetrahydropyrrolo[3,2-f][1,3]benzoxazin-5-carboxylic acids of the general formula (1): or their racemates, or their optical isomers, or their pharmaceutically acceptable salts and/or hydrates possessing the antiviral effect. In compounds of the general formula (1) each R1 and R4 represents independently of one another a substitutes of amino group chosen from hydrogen atom, optionally substituted linear or branched alkyl comprising 3-12 carbon atoms, optionally substituted cycloalkyl comprising 3-10 carbon atoms, optionally substituted aryl or optionally substituted and possibly an annelated heterocyclyl that can be aromatic or nonaromatic and comprising from 3 to 10 atoms in ring with one or some heteroatoms chosen from nitrogen, oxygen or sulfur atoms or their oxides; R2 represents alkyl substitute chosen from hydrogen atom, optionally substituted mercapto group, optionally substituted amino group, optionally substituted hydroxyl; R3 represents lower alkyl or cycloalkyl; R5 represents a substitute of cyclic system chosen from hydrogen atom, optionally substituted linear or branched alkyl comprising 3-12 carbon atoms, optionally substituted cycloalkyl comprising 3-10 carbon atoms, optionally substituted aryl or optionally substituted and optionally an annelated heterocyclyl that can be aromatic or nonaromatic and comprising from 3 to 10 atoms in ring with one or some heteroatoms chosen from nitrogen, oxygen or sulfur atoms or their oxides; R6 represents a substitute of cyclic system chosen from hydrogen atom, halogen atom, cyano group, optionally substituted aryl or optionally substituted and optionally annelated heterocyclyl that can be aromatic or nonaromatic and comprising from 3 to 10 atoms in ring with one or some heteroatoms chosen from nitrogen, oxygen or sulfur atoms or their oxides. Also, invention relates to methods for treatment, drugs and pharmaceutical compositions using compounds of this invention. Proposed compounds can be used as active components of drugs used in treatment of such diseases as infectious hepatitis, human immunodeficiency, atypical pneumonia and avian influenza.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition, improved methods of synthesis.

22 cl, 3 tbl, 6 dwg, 7 ex

FIELD: organic chemistry, medicine, pharmacy, chemical technology.

SUBSTANCE: invention relates to novel substituted esters of 1H-indol-3-carboxylic acids of the general formula (1): or their racemates, or their optical isomers, or their pharmaceutical acceptable salts and/or hydrates. Compounds can be used in treatment of such diseases as infectious hepatitis, human immunodeficiency, atypical pneumonia and avian influenza. In compound of the general formula (1) R1, R41 and R42 each represents independently of one another a substitute of amino group chosen from hydrogen atom, optionally linear or branched alkyl comprising 3-12 carbon atoms, optionally substituted cycloalkyl comprising 3-10 carbon atoms, optionally substituted aryl or optionally substituted and possibly an annelated heterocyclyl that can be aromatic or nonaromatic and comprising from 3 to 10 carbon atom in ring with one or some heteroatoms chosen from nitrogen oxygen or sulfur atoms; or R41 and R42 in common with nitrogen atom to which they are bound form 5-10-membered azaheterocycle or guanidyl through R41 and R42; R2 represents an alkyl substitute chosen from hydrogen atom, optionally substituted mercapto group, optionally substituted amino group, optionally substituted hydroxyl; R3 represents lower alkyl; R5 represents a substitute of cyclic system chosen from hydrogen atom, halogen atom, cyano group, optionally substituted aryl or optionally substituted and possibly an annelated heterocycle that can be aromatic or nonaromatic and comprising from 3 to 10 atoms in ring with one or some heteroatoms chosen from nitrogen, oxygen or sulfur atoms. Also, invention relates to methods for treatment, drugs and pharmaceutical compositions using compounds of this invention.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition, improved method of synthesis.

22 cl, 3 tbl, 8 dwg, 6 ex

FIELD: biotechnology, preparative biochemistry.

SUBSTANCE: method involves hyperimmunization of animal-producers with inactivated, purified and concentrated rabies virus with aluminum phosphate and/or sodium nucleinate as an adjuvant. Virus obtained in culture transplantable cells VERO and in primary culture of Syrian hamster kidney cells is concentrated by adsorption of aluminum phosphate gel or centrifugation, or ultrafiltration methods and purified passing through porous silica, or by ion-exchange chromatography. For immunization antigen with the immunogenicity index 9.5 IU/ml, not less, is used and with the content of protein less 200 mcg/ml, bovine serum albumin less 0.5 mcg/ml Syrian hamster kidney cells and VERO cells less 0.5 mcg/ml, cellular DNA 5.0-10.0 ng/ml, aluminum ions concentration in antigen 0.2-1.25 mcg/ml, and sodium nucleinate 0.002-0.5 mg/ml. Scheme of grund-immunization - 1-3 injections of antigen in the dose 3-15 ml with interval for 14-30 days, the main immunization cycle - on 45-60 day involving 10-15 injections with interval for 5-15 days and in the antigen dose 5-70 ml. Then producers are immunized once per a month with the dose 20-70 ml, and once per 6 month the shortened cycle of immunization is carried out involving 2-4 injections of antigen with interval for 5-15 days in the dose 20-70 ml. Method provides preparing heterologous antirabies serum of high specific activity.

EFFECT: improved preparing method, improved and valuable properties of serum.

12 cl, 1 tbl, 4 ex

FIELD: medicine, gastroenterology.

SUBSTANCE: invention proposes a preparation containing 5-aminosalicylic acid or a substance converting to 5-aminosalicylic acid in body, and lyophilized dried bacterial mass of live bifidobacteria or lactobacilli or their mixture wherein bacteria can be immobilized on sorbent. Components of the preparation are placed into two capsules wherein one capsule comprises bacterial mass of live bacteria and another one comprises mesalazine or sulfasalazine. Proposed invention provides the enhanced effectiveness in treatment of noninfectious inflammatory intestine diseases and reducing treatment period using the proposed preparation. Invention can be used in treatment of noninfectious inflammatory intestine diseases.

EFFECT: valuable medicinal properties of preparation, enhanced effectiveness of treatment.

9 cl, 11 ex

Up!