System delivery and regulated expression of paracrine genes for treatment of cardiovascular and other diseases

FIELD: medicine.

SUBSTANCE: group of inventions can be used to treat heart failure with congestive heart failure (CHF), diabetes or prediabetes in vivo in a patient in need thereof. To this end, a vector is administered to a subject comprising a nucleic acid encoding a paracrine polypeptide or a peptide selected from the group consisting of cardiotonic peptide, urocortin-2 (UCn-2), urocortin-1 (UCn-1), urocortin-3 (UCn-3), brain natriuretic peptide and prostacyclin synthase, wherein the said nucleic acid encoding a paracrine polypeptide or peptide is operably linked to a promoter, wherein the vector is an adeno-associated virus (AAV), and wherein the paracrine polypeptide or peptide is expressed in a cell.

EFFECT: group of inventions provides treatment or improvement of CHF, diabetes or prediabetes in a patient.

24 cl, 20 dwg, 3 tbl

 



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical composition, containing compound of formula or for prevention or treatment of diseases, associated with oxidative stress, selected from group, consisting of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke episodes), MERRF syndrome (myoclonic epilepsy with ragged red fibres) or Kearns-Sayre syndrome, arrhythmia, cardioplegia or myocardium infarction. in formula (1) na stands for 1 or 2, Aa represents 5-membered heteroaryl or heterocycle, each of which has 2 heteroatoms, selected from N, O and S, Rla represents R5a-Xa-Ba-X′a-, Ba represents direct bond, Xa and X′a independently on each other represent direct bond or -OC(O)-, R5a represents hydrogen or 6-9-membered monocyclic or condensed cyclic heterocycle or heteroaryl, each of which has from 1 to 3 heteroatoms, selected from N, O and S, and is optionally substituted with oxo or C1-C6-alkyl, R2a represents -(CR8aR9a)pa-Ya-R7a, pa stands for number from 0 or 1, Ya represents direct bond or -O-, R7a represents hydrogen or phenyl, R3a, R8a, R9a, R10a represent hydrogen, R4a represents -(CH2)pa-Da-R10a-, Da represents C5-cycloalkyl or 6-membered heterocycle, which has 1 heteroatom, selected from N, S and O. Radical values for formula (2) are give in invention formula.

EFFECT: obtaining compositions for prevention or treatment of diseases, associated with oxidative stress.

19 dwg, 5 tbl, 3 ex

Crystals // 2556206

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention describes crystals of 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsulphonyl)acetamide ("compound A"), as a form I of the compound A crystal, which shows diffraction peaks at 9.4 degrees, 9.8 degrees, 17.2 degrees and 19.4 degrees in its power X-ray diffraction spectrum, as a form II of the compound A crystal, which shows diffraction peaks at 9.0 degrees, 12.9 degrees, 20.7 degrees and 22.6 degrees in its power X-ray diffraction spectrum, as a form III of the compound A crystal, which shows diffraction peaks at 9.3 degrees, 9.7 degrees, 16.8 degrees, 20.6 degrees and 23.5 degrees in its power X-ray diffraction spectrum. There are also described methods for producing the forms I, II and III of the compound A crystal, based pharmaceutical composition and PGI2 receptor agonist agent, an accelerating agent for angiogenic therapy, gene engineering or autoimmune bone marrow transplantation, and an accelerating agent for angiogenesis for peripheral artery recovery or angiogenic therapy on the basis thereof; there are also described a preventive or therapeutic agent for a wide range of diseases and conditions.

EFFECT: preparing the new therapeutic agent for the wide range of diseases and conditions.

11 cl, 6 dwg, 6 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: invention represents a mixture of two structural isomers: 2,6-di(1,7,7-trimethylbicyclo[2.2.1]hept-2-yl)-4-methylphenol and its diastereomers, and 2-(1,7,7-trimethylbicyclo[2.2.1]hept-2-yl)-6-(2,2,1-trimethylbicyclo[2.2.1]hept-5-yl)-4-methylphenol, and their diastereomers with the ratio of the first and second structural isomer isomers from 60:40 wt % to 95:5 wt %.

EFFECT: extension of the arsenal of means, possessing simultaneously haemorheological, anti-aggregate, anti-thrombogenic, retinoprotecting, endothelium-protecting, neuroprotecting, anti-arrhythmia and anti-ischemic activity, enhancing the cerebral blood flow.

4 dwg, 20 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to synthetic biologically active heterocyclic substances having antagonist activity on purinoreceptors and which are products of modifying pyridoxin, particularly n-(1,5-dihydro-3-R-8-methyl-9-hydroxy-[1,3]dioxepino[5,6-c]pyridinyl-6-azo)phenyl sulphonic acid and salt forms thereof of general formula I , where is selected from: a hydrogen atom, ethyl, heptyl or octyl.

EFFECT: compounds of the given formula have high antagonist activity on purinoreceptors and can be used in medicine and veterinary.

2 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to use of synthetic biologically active heterocyclic substances as purinoreceptor antagonists, said substances having antagonist activity on purinoreceptors and being a product of modifying pyridoxin, particularly n-(1,5-dihydro-3-R1-3-R2-8-methyl-9-hydroxy-[1,3]dioxepino[5,6-c]pyridinyl-6-azo)phenyl sulphonic acid and salt forms thereof of general formula I , where R1 is a hydrogen atom or methyl, R2 is methyl, isopropyl.

EFFECT: compounds of the given formula have high antagonist activity on purinoreceptors and can be used in medicine and veterinary.

2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula

,

possessing properties of binding with delta opioid receptors. In formula I R1 is selected from the group, consisting of phenyl, pyridinyl and thiazolyl, with R1 being optionally substituted with one or two substituents, independently selected from the group, consisting of C1-4alkoxy, fluorine atom, chlorine atom, bromine atom and cyanogroup; in addition, R1 is optionally substituted with di(C1-4alkyl)aminocarbonyl; Y represents O, S, H3, vinyl, ethinyl or S(O); R2 represents a substituent, selected from the group, consisting of hydrogen, C1-4alkyl, C1-4alkoxy, C1-4alkylthio, fluorine atom, chlorine atom, bromine atom and hydroxy; Ra represents hydrogen or methyl; R3 is selected from the group, consisting of pyrrolidin-2-ylmethyl; pyrrolidin-3-ylmethyl; piperidin-2-ylmethyl, piperidin-3-ylmethyl, piperidin-4-ylmethyl, piperidin-2-ylethyl, piperidin-3-ylethyl, piperidin-4-ylethyl, pyridine-4-yl-(C1-2)alkyl, azetidin-3-ylmethyl; morpholin-2-ylmethyl, morpholin-3-ylmethyl, imidazolylmethyl, thiazolylmethyl, (amino)-C3-6cycloalkyl, 3-hydroxy-2-aminopropyl, 8-azabicyclo[3.2.1]octanyl, 1-azabicyclo[2.2.2]octanyl, guanidinylethyl, 4-(imidazol-1-yl)phenylmethyl, 2-(methylamino)ethyl, 2-diethylaminoethyl, 4-diethylaminobut-2-yl, piperidin-3-yl, piperidin-4-yl and pyrrolidin-3-yl; with piperidin-3-yl being optionally substituted on a carbon atom with phenyl; with pyrrolidin-2-yl in pyrrolidin-2-yl-methyl, pyrrolidin-3-yl, piperidin-3-yl and piperidin-4-yl being optionally substituted on a nitrogen atom with methyl, phenylmethyl, phenethyl or methylcarbonyl.

EFFECT: compounds can be used in the treatment of pain, induced by diseases or conditions, such as osteoarthritis, rheumatoid arthritis, migraine, burn, fibromyalgia, cystitis, rhinitis, neuropathic pain, idiopathic neuralgia, toothache, etc.

24 cl, 3 tbl, 19 ex

Hypotensive means // 2554815

FIELD: medicine.

SUBSTANCE: invention represents a hypotensive means, which contains felodipinum as an active component, as well as target additional components: mesoporous silicon dioxide, lactose, hypromeloza. Realisation of the invention ensures the high technological efficiency of the claimed medical means production with the provision of a prolonged release of an active substance with the application of available components. Felodipinum is included into spherical particles with a highly developed mesoporous structure of silicon oxide.

EFFECT: increase of stability in storage and protection from unfavorable environmental factors.

4 cl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of structural formula I

which can be used for protecting cardiomyocytes or for preventing or treating a disease or a disorder related to cardiomyocyte apoptosis. In formula I A represents =S, -SR4 or =O, X represents F, Cl, Br or I, R1 represents phenyl, R2 and R3 are connected to form morpholine, and R4 represents C1-C6-alkyl.

EFFECT: invention refers to using the compound for producing the therapeutic agent for protecting cardiomyocytes or for preventing or treating a disease or a disorder related to cardiomyocyte apoptosis, and to the method for producing the above compounds.

8 cl, 2 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds of formula I, possessing ability of binding with delta-opioid receptors. In formula R1 is selected from the group, consisting of i) phenyl, optionally substituted with one-two substituents, independently selected from the group, consisting of C1-4alkyl, C1-4alcoxy, C1-4alkylthio, hydroxyl, di(C1-4alkyl), aminocarbonyl, chlorine and fluorine, in such a way that only one di(C1-4alkyl)aminocarbonyl is present; ii) naphthyl; iii) pyridinyl, optionally substituted with one substituent, selected from the group, consisting of C1-4alkyl, C1-4alcoxy, C1-4alkylthio, hydroxy, fluorine, chlorine and cyano; iv) pyrimidin-5-yl; v) furanyl; vi) thienyl; vii) 5-oxo-4,5-dihydro-[1,2,4]oxodiazol-3-yl; and viii) di(C1-2alkyl)aminocarbonyl; Y represents ethyl, vinyl or bond; or Y represents O, when R1 represents optionally substituted phenyl, where substituent represents C1-4alcoxy; R2 represents phenyl, optionally substituted with one-two substituents, independently selected from the group, consisting of C1-4alkyl, C1-4alcoxy, fluorine, chlorine and cyano, trifluoromethoxy and hydroxy; or R2 represents phenyl, substituted with one aminocarbonyl, di(C1-4alkyl)aminocarbonyl, C1-4alcoxycarbonyl or carboxysubstituent; R3 is selected from the group, consisting of i) 3-aminocyclohexyl; ii) 4-aminocyclohexyl; iii) piperidin-3-yl; iv) piperidin-4-yl; v) pyrrolodin-2-yl-methyl, in which pyrrolodin-2-yl is optionally substituted by 3-rd or 4-th position with one or two fluorine-substituents; vi) azetidin-3-yl; vii) 2-(N-methylamino)ethyl; viii) 3-hydroxy-2-aminopropyl; ix) piperidin-3-yl-methyl; x) 1-azabicyclo[2.2.2]octan-3-yl; and xi) 8-azabicyclo[3.2.1]octan-3-yl; or R3 together with Ra and nitrogen atom, which they both are bound to, form piperazinyl, optionally substituted with 4-C1-4alkyl; Ra represents hydrogen, 2-(N-methylamino)ethyl or C1-2alkyl, optionally substituted with azetidin-3-yl.

EFFECT: compounds can be used in treatment of pain in the range from medium to strong, caused by diseases or conditions, such as osteoarthritis, migraine, burn, fibromyalgia, cystitis, rhenite, neuropathic pain, idiopathic neuralgia, toothache, etc.

21 cl, 4 tbl, 26 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to 3-phenylpropionic acid derivatives of formula

wherein R1A represents hydrogen, methyl, ethyl, cyclopropyl or cyclobutyl, R1B is hydrogen or methyl, R2A represents hydrogen, methyl, trifluoromethyl, ethyl or n-propyl, R2B is hydrogen or methyl or R1A and R2A are combined together, and in a combination to carbon atoms to which they are attached, form a cyclopropyl ring of formula

wherein R1B and R2B have the values as specified above, or R2A and R2B are combined together, and in a combination to a carbon atom, to which they are attached, form a cyclic group of formula or

wherein n means a number 1 or 2, R3 is hydrogen, fluorine or methyl, R4 represents hydrogen, fluorine, chlorine or a cyanogroup, R5A represents methyl, R5B is trifluoromethyl or R5A and R5B are combined together, and in a combination to a carbon atom, to which they are attached, form a difluorosubstituted cycloalkyl ring of formula or

R6 represents chlorine, alkyl with 1-4 carbon atoms, alkenyl with 2-4 carbon atoms, cyclopropyl or cyclobutyl; alkyl with 1-4 carbon atoms and alkenyl with 2-4 carbon atoms can contain up to three fluorine atoms, cyclopropyl and cyclobutyl up to three fluorine atoms as substitutes, and R7 represents hydrogen, fluorine, chlorine, methyl or a methoxy group. The invention also refers to a therapeutic agent containing the above compounds and to a method for producing the compounds of formula (I).

EFFECT: compounds of formula (I) activate the form of soluble haem-free guanylate cyclase and are applicable in the method of treating and/or preventing cardiac failure, angina, hypertension, pulmonary hypertension, ischemia, vascular diseases, disturbed microcirculation, thromboembolic diseases and arterial sclerosis.

6 cl, 4 tbl, 113 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to the field of immunology. Claimed is the application of a monoclonal antibody against a protein of a human Fas ligand (CD95L, or Apo1L, or FasL) or its antigen-binding fragment for manufacturing a medication for the prevention and/or treatment of skin diseases, associated with the acantholysis of keratinocytes, in particular for the prevention and/or treatment of pemphigus, where the antibody contains amino acid sequences CDR of the antibody NOK-2, F919-7-3, F918-9-4 or F919-9-18 or is produced by the hybridoma ATCC PTA-5045, ATCC PTA-5533, ATCC PTA-5534 or ATCC PTA-5535.

EFFECT: application of the antibodies by the invention or their antigen-binding fragments provides the effective blocking of mechanisms, resulting in pemphigus lesions.

7 cl, 14 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to biotechnology, namely, to peptide for stimulation of Hsp70 (heat shock protein 70) or for protection of skin against ultraviolet radiation. Peptide can be represented by peptide with general formula R1-AA1-AA2-AA3-AA4-R2, its stereoisomers, their mixture and/or their cosmetically or pharmaceutically acceptable salt. AA1 represents -His-; AA2 is selected from the group, consisting of -His-, -Leu- and -Pro-; AA3 represents -Leu-; AA4 is selected from the group, consisting of -Arg- and -Asn-.

EFFECT: claimed invention makes it possible to obtain novel peptide, which is effective for stimulation of Hsp70 synthesis or for protection of skin against ultraviolet radiation.

17 cl, 1 tbl, 16 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to oxazolopyrimidine compounds of formula (I) , in which A is selected from NH, O and S; R1 is selected from (C1-C6)-alkyl, (C3-C7)-cycloalkyl-CtH2t and Het-CtH2t-, where t is selected from 0, 1, 2 and 3; R2 is selected from phenyl and residue of aromatic 5-member - 6-member monocyclic heterocycle, which includes 1, 2 similar or different ring heteroatoms, selected from N, O and S, in which one of ring nitrogen atoms can carry atom of hydrogen or substituent R21, and in which phenyl and aromatic heterocycle residue are optionally substituted in one or more ring carbon atoms with one or more similar or different substituent R22; R3 is selected from (C1-C6)-alkyl, or R3 represents residue of saturated or unsaturated 3-member - 10-member, monocyclic or bicyclic ring, which includes 0, 1, 2 or 3 similar or different ring nitrogen atoms can carry hydrogen atom or (C1-C4)-alkyl substituent and one or two ring sulphur atoms can carry one or two oxo groups, and in which ring residue is optionally substituted in one or more ring carbon atoms with similar or different substituents R31, on condition that R3 cannot be (C1-C6)-alkyl, if A represents S; other values of radicals are given in i.1 of formula.

EFFECT: compounds of formula (I) are suitable for wound healing.

16 cl, 2 tbl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to field of immunology. Claimed is application of monoclonal antibody against human Fas ligand protein (CD95L, or Apo1L, or FasL) or its antigen-binding fragment for manufacturing medication for prevention and/or treatment of skin diseases, associated with acantholysis of keratinocytes, in particular for prevention and/or treatment of pemphigus, where antibody contains amino acid sequences CDR of 3E1 antibody or is produced by hybridoma ATCC PTA-4017.

EFFECT: application of antibody in accordance with invention or its antigen-binding fragment provides more effective prevention of desmoglein (dsg3) cleavage in comparison with application of other antibodies.

11 cl, 16 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutics and represents a suspension for treating psoriasis, containing calcipotriol monohydrate in the form of nanocrystals having the particle size distribution within the range of 200-600 nm; the particles are dispersed in an aqueous phase containing a non-ionic polymer surfactant specified in a group consisting of a surfactant in the form of poloxamers or polysorbates, in the amount of 0.01-5 wt % calculated using a suspension for preventing development of aggregation and/or calcipotriol monohydrate nanocrystal growth; the calcipotriol monohydrate nanocrystals are produced in the suspension by processing the suspension by a method involving the stages of reduction in crystalline calcipotriol monohydrate particle size in an aqueous phase to form microparticles having the particle size distribution within the approximate range of 5-20 mcm and the average approximate particle size of 10 mcm; the suspension is exposed to three high-pressure homogenisation cycles for 7-15 minutes each; in the first, second and third cycles, the pressure makes 300-800 bars, 800-1,200 bars and 1,200-1,700 bars respectively.

EFFECT: invention provides creating the local composition containing calcipotriol as an active agent, however being free from propylene glycol as a solvent.

34 cl, 8 ex, 5 tbl, 9 dwg

FIELD: medicine.

SUBSTANCE: to improve functional-aesthetic results of the plastic surgery of post-traumatic eyelid deformations, starting from 7-8 day from the moment of carrying out blepharoplasty of the post-traumatic cicatrical eyelid deformation, immediately after the removal of operational sutures, on the operated zone of the eyelid performed is a procedure of magnetic-photophoresis of a medical solution, made from 3000 ME of longidaze, 3 ml 25% solution of dimethylsulphoxide and 1 ml 0.25% solution of derinate, with 2 ml of the prepared solution being applied on an autodermal transplant and healthy skin surrounding it, with up to 1 cm indent from the wound edge, after 3-5 minutes a gauze pad, soaked with 2 ml of the remaining prepared solution, is applied on the processed surface of skin with the further 10 minute impact by a contact method by a travelling pulsed magnetic field of the apparatus "AMO-ATOS" with the frequency of pulse consecution of 5-10 Hz. Then, after the pad is removed, without the time interval, borders of the autodermal transplant and healthy skin closing are processed by infrared laser irradiation of a range of 0.89 mcm of the apparatus UZOR-2K with the frequency of the pulse repetition rate of 1500 Hz, in accordance with a contact labile method, 1 minute on each field, with carrying out 1 procedure daily for 10 days.

EFFECT: improvement of the quality of skin transplant engraftment, absence of secondary eyelid deformations, and reduction of the post-operational treatment duration.

1 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to cosmetology, namely represents a composition containing minoxidil and/or minoxidil sulphate combined with additives containing at least one antioxidant, at least one organic acid and selected fatty acids mixture. Besides, the invention refers to using the compounds for hair growth enhancement/recovery and/or hair loss prevention in mammals, particularly in a human.

EFFECT: using the invention provides faster anagen phase in mammalian hair growth and/or enhanced terminal hair above the skin surface by local application the declared compositions.

19 cl, 9 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to medicine, namely to dermatology, and can be used for preventing and/or treating skin itching. It involves using L-serine as a therapeutic agent, a pharmaceutical composition containing L-serine, as well as a dermato-cosmetic composition containing L-serine as a single active agent, Avene Thermal Spring Water, glycerine and a cosmetically acceptable carrier. The L-serine concentration in the composition makes from 0.01 wt % to 10 wt % in relation to the total weight of the composition. More preferentially, the concentration makes 0.5 wt % to 3 wt % in relation to the total weight of the composition.

EFFECT: group of inventions provides the effectiveness of application.

8 cl, 2 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions relates to medicine, namely to dermatology and mycology, and can be applied in the treatment of skin and its appendages. A pharmaceutical composition for external application contains nanoparticles for the laser thermotherapy of infectious affections of the skin and its appendages. The nanoparticles are characterised by, at least, one localised surface Plasmon resonance in the range of a wavelength from 400 to 1100 nm. The nanoparticles are dispersed in a physiologically acceptable carrier, which is characterised by the absence of the absorption or weak absorption and/or weak dispersion of light radiation in the said range of wavelengths and possessing biocidal properties. The pharmaceutical composition is applied on an affected area and irradiated by laser radiation with a wavelength close to the wavelength of the localised surface Plasmon resonance of the nanoparticles, contained in the composition, or equal to it. The irradiation is continued until the desirable temperature of heating of the said area is achieved.

EFFECT: group of inventions ensures an increased treatment efficiency, reduction of a risk of development of side effects, reduction of the number of recurrences due to the application of the pharmaceutical composition, capable of absorbing energy of the light radiation and transforming it into heat energy with the achievement of the specified temperature with laser irradiation at the specified wavelength with the lower intensity of laser radiation and possessing biocidal properties.

63 cl, 3 dwg, 1 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to the pharmaceutical industry and represents a pharmaceutical composition for the external application for the treatment of skin diseases in the form of a cream, which includes as an active substance methylprednisolone aceponate in a therapeutically effective amount and a lipophilic base, characterised by the fact that as the lipophilic base it contains petrolatum, liquid paraffin and oil of castor oil plant seeds and additionally white bee wax, with the components of the composition being in a specified ratio in g/100 g of the composition.

EFFECT: invention provides the creation of the stable composition, improved pharmacological properties and absence of an irritating effect.

1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry and represents a pharmaceutical composition for control of pain accompanying individual's joint diseases containing hyaluronic acid, which is cross-linked by cycling a double bond in a group of cinnamic acid in partially amidated hyaluronic acid presented by formula (1) to form a cyclobutane cycle, wherein in the above formula, Ar represents a phenyl group, n is equal to an integer 2 or 3; HA represents a carboxy residue of hyaluronic acid, and m represents a relation of amidation of hyaluronic acid to all the carboxyl groups and is equal to 3-50% in relation to all the carboxyl groups, and a pharmaceutically acceptable carrier, wherein the pharmaceutical composition represents a product for injection, wherein the pharmaceutical composition represents the product for injection, wherein the amount of the cross-linked hyaluronic acid makes 1 wt % at the total amount of the product for injection, wherein a single dose of the product for injection makes 2-3 ml, wherein the pharmaceutical composition represents a single-use preparation, which is administered every 13 weeks and more.

EFFECT: invention provides the extremely long analgesic action after the single administration, earlier onset of the analgesic action.

15 cl, 1 dwg, 5 tbl, 1 ex

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