Method for treatment of diseases related to masp-2-dependent activation of complement (versions)
SUBSTANCE: medicinal agent for inhibition of MASP-2-dependent complement is an agent containing an antibody or its fragment, bound with a full-size polypeptide MASP-2, but not bound with a MASP-2 N-terminal fragment containing CUBI-EGF-CUBII domains and not bound with a MASP-2 C-terminal fragment, containing of CCPII-SP domains.
EFFECT: invention makes it possible to selectively inhibit MASP-2-dependent activation of complement, at the same time leaving Clq-dependent classic path of complement activation as functionally unaffected.
9 cl, 39 dwg, 7 tbl, 31 ex
The text descriptions are given in facsimile form.
1. Agent, inhibiting MASP-2, designed for use as a drug, selectively inhibiting MASP-2-dependent activation of the complement, while leaving functionally unaffected Clq-dependent classical pathway of activation of complement, where the said agent comprises an antibody or fragment to bind to the full-length polypeptide MASP-2, which is a sequence of SEQ ID NO:6, but does not bind to MASP-2 N-terminal fragment consisting of CUBI-EGF-CUBII domain and does not bind to MASP-2 C-terminal fragment consisting of CCPII-SP domains.
2. The agent according to claim 1, where the agent, inhibiting MASP-2, specifically binds to the polypeptide comprising the sequence of SEQ ID NO:6 with an affinity of at least 10 times greater than in the case of linking an excellent antigen in the complement system.
3. The agent according to claim 1, where the agent, inhibiting MASP-2, representing the antibody or its fragment that specific image associated with a segment of the sequence SEQ ID NO:6, for example, where the antibody or fragment is a monoclonal or polyclonal, or recombinant antibody, or where the antibody has reduced effector function, or dianthicola presents chimeric, humanized or human antibody, or where the antibody obtained in MASP-2 insufficient transgenic animal cells.
4. A method of inhibiting MASP-2-dependent activation of the complement of a mammal object, suffering from indirect MASP-2-dependent complement, which includes an introduction to the mammalian subject a quantity of an agent that inhibits MASP-2, effective for the selective suppression of MASP-2 dependent activation of complement, while leaving functionally unaffected Clq-dependent classical pathway of activation of complement, where the agent, inhibiting MASP-2, is an antibody or fragment to bind to the full-length polypeptide MASP-2, which is a sequence of SEQ ID NO:6, but does not bind to MASP-2 The N-terminal fragment consisting of CUBI-EGF-CUBII domains, and does not bind to MASP-2 C-terminal fragment consisting of CCPII-SP domains.
5. The method according to claim 4, where the agent, inhibiting MASP-2 specifically binds to a polypeptide comprising the sequence of SEQ ID NO:6.
6. The method according to claim 4, where the agent, inhibiting MASP-2, is an antibody or fragment that specifically binds to a segment of the sequence SEQ ID NO:6, for example, where the antibody or fragment is a monoclonal, or where the antibody presents chimeric, GU is Anisimovna or human antibody or where the antibody obtained in MASP-2 insufficient transgenic animal cells.
7. The method according to claim 4, comprising the administration to a mammal object of the amount of agent that inhibits MASP-2, effective for:
(i) the treating facility, suffering from a MASP-2-dependent complement-mediated vascular insufficiency, including the introduction amount of an agent that inhibits MASP-2, effective to inhibit MASP-2-dependent activation of complement, where vascular insufficiency preferably belongs to the group of the following diseases: cardiovascular disease, cerebrovascular insufficiency, peripheral (e.g., musculoskeletal) vascular insufficiency, renovaskulyarnoy failure, mesenterina/enteric vascular failure, revascularization (restoration of vessels in any tissue or organ) transplantation or/and reimplantations, vasculitis, disease shenleyn's disease (Henoch-Schonlein purpura), nephritis, vasculitis, due to systemic lupus erythematosus, vasculitis, due to rheumatoid arthritis, immune complex vasculitis, Takayasu's arteritis (sickness absence of pulse), dilated cardiomyopathy, diabetic angiopathy, Kawasaki syndrome (syndrome T4 - hyperlattices, Takayasu), venous air embolism (VDE), and restenosis (re-narrowing of the issue is the ETA of any authority after its enlargement surgery) due to the introduction of the stent, rotational atherectomy and percutaneous transluminal coronary angioplasty (RTSA); or
(ii) treatment of the object, suffering from a MASP-2-dependent complement mediated condition associated with ischemia-reperfusion injury, preferably ischemia and reperfusion injury associated with aneurysm repair ports, extracorporeal circulation, vascular reanastomosis due to organ transplantation or/and re limbs/fingers, stroke, myocardial infarction and hemodynamic resuscitation after a shock or/and surgical intervention;
(iii) the treatment or/and prevention of atherosclerosis in monitoring object when appropriate, or
(iv) treatment of the object, suffering from a MASP-2-dependent complement-mediated disease caused by inflammatory gastrointestinal disorders, preferably gastrointestinal disturbance selected from the group consisting of pancreatitis, granulomatous disease (Crohn's disease), ulcerative colitis, irritable bowel syndrome, and diverticulitis; or
(v) treatment of the object, suffering from a MASP-2-dependent complement-mediated pulmonary disease, preferably pulmonary disease is selected from the group consisting of the following: acute respiratory distress syndrome, transfusion-induced lung damage (TRALI), acute ischemic-reperfusion pulmonary disease, chronic obstructive pulmonary disease, asthma, non-infectious necrotic Wegener (Wegener's granulomatosis), disease glomerular basement membrane disease Goodpasture)syndrome meconial aspiration syndrome obliterating bronchiolitis, idiopathic pulmonary fibrosis, acute lung injury due to burns, nicardipine pulmonary edema, transfusion-induced depression of breath and emphysema; or
(vi) treatment of the object, which was, is or will be the procedure for in vitro reperfusion, preferably procedure extracorporeal reperfusion selected from the group consisting of the following diseases: hemodialysis, plasmapheresis, leukocytopenia, extracorporeal membrane oxygenator (ECMO), heparin-induced extracorporeal membrane oxygenation with precipitation of LDL - HELP), and extracorporeal circulation (SRV); or
(vii) treatment of the object, suffering from a MASP-2-dependent complement-mediated skeletal muscle disease, preferably musculoskeletal disease selected from the group consisting of the following diseases: osteoarthritis, rheumatoid arthritis, of still's disease (a form of rheumatoid arthritis in children), gout, neurogenic arthropathy, psoriatic arthritis, spondyle ropati, fragmentary arthropathy, muscular dystrophy, and systemic lupus erythematosus (SLE); or
(viii) treatment of the object, suffering from a MASP-2-dependent complement-mediated renal disease, preferably renal disease selected from the group consisting of the following diseases: mesangiocapillary glomerulonephritis, membranous glomerulonephritis, membranosa-proliferative glomerulonephritis (mesangiocapillary glomerulitis), acute post-infectious glomerulitis (poststreptococcal glomerulitis), cryoglobulinaemic glomerulonephritis, lupus nephritis, nephritis as a complication of disease Shenleyn's disease and Berger disease (IgA nephropathy); or
(ix) the treating facility, suffering from a MASP-2-dependent complement-mediated skin disease, preferably a skin disease selected from the following groups of diseases: psoriasis, autoimmune bullous dermatitis, eosinophilic interstitial edema, bullous pemphigoid acquired bullous bullosa, herpes pregnant, damage due to thermal and chemical burns; or
(x) the treatment of the object, which was, is or will be the procedure for transplantation of organs or tissues, preferably the transplant procedure selected from the group consisting of allotransplantation organs, xenotransplantation of organs, and per the cages tissues: or
(xi) the treating facility, suffering from a MASP-2-dependent complement mediated condition associated with disorders or damage to the nervous system, preferably a violation of or damage to the nervous system selected from the following groups of diseases: multiple sclerosis, progressive myasthenia gravis, Huntington's disease, amyotrophic lateral sclerosis, infectious polyneuritis (syndrome Guillain Barre), post-traumatic reperfusion, reborn ROM, cerebral trauma, Parkinson's disease, Alzheimer's disease, syndrome, Miller-Fisher, cerebral trauma and/or hemorrhage, demyelinization (destruction of the myelin nerve fiber layer) and meningitis, or
(xii) treatment of the object of observation, suffering from a MASP-2-dependent complement-mediated blood diseases, preferably a blood disorder selected from the group consisting of the following diseases: sepsis, severe sepsis complications, septic shock syndrome, systemic inflammatory response syndrome of acute respiratory failure as a concomitant disease with sepsis, a syndrome of systemic inflammatory response, hemorrhagic collapse, hemolytic anemia, autoimmune thrombocytopenic greengourmet syndrome and hemolytic uremia; or
(xiii) treatment of the object of observation, suffering from a MASP-2-dependent compleme is the indirect urogenital disease, preferably urogenital disease selected from the group of the following diseases: syndrome, painful bladder, overactive bladder, bacterially cystitis, interstitial cystitis, infertility, placental dysfunction (failure) and spontaneous abortion and pre-eclampsia (late toxicosis of pregnant women); or
(xiv) treatment of the object of observation, suffering from a MASP-2-dependent complement-mediated diabetes no inclination to obesity (diabetes mellitus type 1 or insulin-dependent diabetes mellitus or/and complications due to type 1 diabetes or type 2 (attack in adults), preferably where the complication associated with type 1 diabetes or type 2 is selected from the group consisting of angiopathy, neuropathy, and retinopathy; or
(xv) the treatment of the object of observation, which was, is or will be chemotherapy or/and radiotherapy; or
(xvi) the treating facility, suffering from malignant disease; or
(xii) the treating facility, suffering from endocrine diseases, preferably endocrine disease selected from the group consisting of the following medical conditions: Hashimoto's thyroiditis, stress, symptoms of anxiety, hormonal disorders affecting the regulated secretion of prolactin, growth of tumors Il the other factors, provoked insulin-dependent States and adrenocorticotropic hormone from the pituitary gland; or
(xiii) the treating facility, suffering from a complement-mediated ophthalmologic disease, preferably where the ophthalmological disease is age-related macular degeneration.
8. Composition for inhibiting MASP-2-dependent activation of complement, comprising a therapeutically effective amount of an agent that inhibits MASP-2 disclosed in claims 1, 2 or 3 and a pharmaceutically acceptable carrier.
9. Method for the production of medicaments for use in the inhibition effects of MASP-2-dependent activation of the complement of a living mammal object, suffering from indirect MASP-2-dependent complement, comprising combining a therapeutically effective amount of an agent that inhibits MASP-2 disclosed in claims 1, 2 or 3, in a pharmaceutical carrier.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to medicine. What is presented is an antibody produced of hybridoma ATCC No. PTA-7580 specific to human protein tyrosine phosphatase beta (HPTPβ). What is described is a Fab version of said antibody, as well as versions of method of treating and pharmaceutical compositions based on the use of the antibodies. Binding the antibody and HPTPβ intensifies Tie-2 signal transmission, and thereby increases angiogenesis, whereas binding the Fab antigen-binding antibody fragment and HPTPβ inhibits Tie-2 signal transmission, and thereby reduces angiogenesis.
EFFECT: use of the invention can find application in medicine for treating the diseases related to disturbed angiogenesis.
21 cl, 12 dwg, 1 tbl, 5 ex
SUBSTANCE: invention relates to biotechnology and represents antibody, which is bound with human hepatocyte growth factor activator (HGFA). Also described is method of treating disease associated with impaired regulation of HGF/c-met-mediated signal that applies antibody.
EFFECT: invention can be efficiently used in treatment of diseases, associated with regulation of HGF/c-met-mediated signal.
18 cl, 23 dwg, 1 tbl, 1 ex
FIELD: biology, biotechnologies.
SUBSTANCE: invention can be used in the food-processing industry. For obtaining of 6-O-αD-(1,6-GPS) isomaltulose would submit to the reactionary solution containing enzyme, possessing ability of catalyzing transformation of isomaltulose in 1,6-GPS from which allocate a target product after an incubation at temperature of 20-40°C. Before or during incubation in a reactionary solution add regenerative equivalents. Allocate enzyme with means of anion exchange and two affine chromatography from a crude extract of a microorganism of sort Gluconobacter containing a gene of enzyme, possessing ability of catalyzing transformation of isomaltulose in 1,6-GPS. The nucleic acid coding enzyme, possessing ability to catalyze transformation of isomaltulose in 1,6-GPS is obtained. The vector containing given nucleic acid, is intended for provision of an expression of this enzyme in a host cell.
EFFECT: invention application allows obtaining 6-O-αD-D-D-sorbite from isomaltulose by means of the unique enzymatic reaction.
26 cl, 2 dwg, 1 tbl, 4 ex
FIELD: biotechnological methods.
SUBSTANCE: invention concerns new polynucleotides, which encode polypeptide having tripeptidylpentidase activity. To produce this polypeptide, host cell is transformed with polynucleotide or polynucleotide-containing vector and then cultured under suitable polynucleotide expression conditions.
EFFECT: enabled production of new protease from thread fungi.
14 cl, 3 tbl, 11 ex
FIELD: biotechnology, biochemistry, enzymes.
SUBSTANCE: invention reports about preparing a polypeptide possessing with the biological activity of enzyme protein-histidine-phosphatase and a polynucleotide encoding this enzyme also. Based on the polypeptide a pharmaceutical preparation is prepared using in pathological states associated with disturbance function of protein-histidine-phosphatase. Also, antibodies showing specificity to sites of indicated polypeptide are prepared. The use of the invention provides study of the N-phosphorylation process, carrying out the diagnosis of pathology of cellular regulation and growth cells and to regulate pathological states associated with disturbance in function of protein-histidine-phosphatase. Invention can be used in medicine and pharmacy.
EFFECT: valuable medicinal properties of enzyme, improved preparing method.
11 cl, 3 tbl, 10 dwg
SUBSTANCE: invention relates to proteins and polynucleotides, which stimulate enzyme cleavage and releasing of TNF receptors. Also disclosed are methods for identification of additional agents, which influence on TNF receptor releasing from cells. Products of present invention containing in pharmaceutical compositions as active ingredients increase or decrease TNF signal transduction and consequently abate disease pathology.
EFFECT: new pharmaceutical compositions.
27 cl, 8 ex, 3 tbl, 5 dwg
FIELD: genetic engineering, biotechnology, biochemistry, medicine.
SUBSTANCE: invention represents a polypeptide of new family of phosphodiesterases and a polynucleotide encoding thereof. Invention relates to the development of methods for detecting partners in specific binding indicated polypeptide and polynucleotide involving stages for their contacting with a compound, detection for binding and detection a compound as a partner for specific binding. Also, invention proposes the constructed expression construction that is used in the method for preparing polypeptide of new family of phosphodiesterases for preparing a cell-producer. Also, monoclonal and polyclonal antibodies raised to this polypeptide have been prepared. Invention describes anti-sense polynucleotide for regulation of expression of polypeptide of new family of phosphodiesterases. Using the invention provides additional pharmacological approaches in treatment of states associated with disturbance of metabolic ways of cyclic nucleotides.
EFFECT: valuable medicinal and biochemical properties of polypeptide.
27 cl, 3 tbl, 11 ex
FIELD: genetic engineering, in particular genes for cell cycle controlling point.
SUBSTANCE: polynucleotide encoding rad3 polypeptide ATR homologue is cloned into expression vector, having functionality in eucariotic cells. Polypeptide of rad3 polypeptide ATR homologue is obtained by cultivation of eucariotic cell culture, transformed by vector. Monoclonal antibody to rad3 polypeptide ATR homologue is obtained by hybridoma technologies. Polyclonal antibodies are obtained by inoculation of rad3 polypeptide ATR homologue in host animal. Polynucleotide presence in animal tissue sample is detected by contacting of this sample containing DNA or RNA with polynucleotide encoding rad3 polypeptide ATR homologue under hybridization conditions. Polypeptide in biological sample is detected by sample contact with monoclonal or polyclonal antibodies. Substances having anticancer activity are screened on the base of reduced activity of ATR polypeptide on substrate or reduced chelating of ATR homologue in presence of candidate substance. Present invention makes it possible to produce human or S.pombe rad3 polypeptide ATR homologue and is useful in investigation ATR role as gene for cell cycle controlling point in cell culture in vivo or in vitro.
EFFECT: new anticancer substances.
24 cl, 1 dwg
SUBSTANCE: invention relates to novel 5-halogen-substituted oxindole derivatives of formula I: , where: R1 denotes hydrogen, methoxy or ethoxy group; R2 denotes hydrogen or a methoxy group; R3 denotes hydrogen, methyl, ethyl, n-propyl or isopropyl; R4 denotes an ethoxy or isopropoxy group; R5 denotes H or methyl; R6 denotes Cl or F; X1 denotes O, NH or CH2; X2 and X3 denotes N or CH under the condition that X2 and X3 do not denote N at the same time; as well as pharmaceutically acceptable salts thereof. The invention also relates to pharmaceutical compositions for treating and/or preventing vasopressin-dependent diseases, which contain derivatives of formula I, and use thereof in treating vasopressin-dependent diseases.
EFFECT: high efficiency of using said compounds.
25 cl, 8 ex, 2 tbl
SUBSTANCE: invention refers to medicine, namely cardiology and concerns treating the patients with ST segment elevation acute myocardial infarction. That is ensured by the two-bolus intravenous administration of the thrombolytic preparation Fortelysine in a dose of 10 mg, and 30 minutes later in a dose of 5 mg.
EFFECT: presented mode of administration of Fortelysine provides the effective recovery of the antegrade coronary blood flow in the infarction-involved coronary artery in the patients with ST segment elevation acute myocardial infarction.
SUBSTANCE: invention relates to medicine, particularly to pharmacology in cardiology, particularly to a method of treating the adolescents with essential arterial hypertension. The method of treating the adolescents with essential arterial hypertension consists in taking an aqueous infusion of herbal tea containing dried ground herbal raw material: crowberry herb, meadow rue herb, cudweed herb, honeyberry fruit; and in taking an oxygen phytococktail prepared of said herbal tea, licorice root extract and a syrup having hypotensive and diuretic action.
EFFECT: method is effective for treating the adolescents with essential arterial hypertension; it has no side effects and counter-indications.
SUBSTANCE: invention refers to medicine, namely therapy and physiotherapy and may be used for lipid metabolism correction in individuals with a risk of developing atherosclerosis. For this purpose with underlying basic health resort treatment, weak and medium mare's milk of a Turner degree of 71-100° in the amount of 200-250 ml three times a day, 15-20 minutes before meals; herbal tea "Lan" combined with hydrocarbonate sulphate-calcium magnesium low-mineralised mineral water at 3-4 ml per 1 kg of body weight three times a day 15-20 minutes before meals. The length of the therapeutic course is 24 days.
EFFECT: effect with the use of natural therapeutic factors provides the effective correction of lipid metabolism ensured by lowering atherogenic lipids, increasing CS HDLP, inhibiting lipid peroxidation and enhancing the activity of antioxidant enzymes.
3 tbl, 2 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to a combined antihypertensive drug containing an agent presented by Amlodipine besilate and Lisinopril dehydrate mixed with an excipient. As the excipient, the specified antihypertensive drug contains microcrystalline cellulose of an average particle size of 90-100 mcm and a bulk density of 0.28-0.33 g/ml; as additives, it contains colloidal silicon dioxide, magnesium stearate and sodium carboxymethyl starch. The invention also refers to a method for preparing the mentioned antihypertensive drug by direct compression.
EFFECT: providing a stable drug preparation, more storage-stable, having high producibility, active substance distribution uniformity and bioavailability.
8 cl, 2 tbl, 3 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: claimed invention relates to field of pharmaceutics and medicine and deals with pharmaceutical composition or therapeutic combination for treatment of vascular pathological states, diabetes, obesity and reduction of concentration of sterols in plasma, which include: (a) at least, one activator of peroxisome proliferator-activated receptor, selected from group, consisting of fenofibrate, clofibrate, gemfibrozil, cyprofibrate, bezafibrate, clinofibrate, binifibrate, lifibrole or their mixture, and (b) sterol absorption inhibitor, represented by formula
, or its pharmaceutically acceptable salt.
EFFECT: claimed are combinations of activator (activators) of peroxisome proliferator-activated receptor (ppar), and inhibitor (inhibitors) of sterol absorption and treatment of vascular diseases.
FIELD: medicine, pharmaceutics.
SUBSTANCE: claimed invention relates to medicine, namely to solid peroral dosage form, obtained by rotation pressing, which includes therapeutically effective quantity of aliskiren or its pharmaceutically acceptable salt, and active ingredient is present in said dosage form in amount higher than 38% by weight of peroral dosage form, as well as to method of obtaining said solid peroral dosage form.
EFFECT: method with application of rotational pressing makes it possible to exclude application of solvent, requires for wet granulation, method ensures high content of drug agent in composition.
23 cl, 2 ex
SUBSTANCE: invention relates to medicine, namely to cardiology, and can be used for prevention of acute coronary syndrome in men with arterial hypertension, with moderate risk of acute cardiovascular complications. Multispiral computed tomography is carried out and total volume of calcium or total calcium index is determined by Agatson. Value of total calcium volume higher than 1222 or total calcium index higher than 1519 is considered to be significant additional factor. Such patients are additionally given therapy with acetylsalicylic acid.
EFFECT: method extends indications for carrying out said therapy with moderate cardiovascular risk and asymptomatic course of atherosclerosis, which ensures prevention of acute coronary syndrome in such patients.
2 tbl, 1 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: present invention refers to new compounds of general formula I [X]n-Y-ZR1R2, wherein the radicals are specified in the description, effective as heparan sulphate-binding protein inhibitors. The invention also refers to a pharmaceutical or veterinary composition having heparan sulphate-binding protein inhibitory activity for preventing or treating a disorder in a mammal, and to the use of these compounds and compositions for antiangiogenic, antimetastatic, anti-inflammatory, antimicrobial, anticoagulant and/or antithrombotic therapy in a mammal.
EFFECT: preparing the new compounds of general formula I [X]n-Y-ZR1R2, wherein the radicals are specified in the description, effective as the heparan sulphate binding protein inhibitors.
10 cl, 31 ex, 11 tbl, 40 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to derivatives of Ice formula and the use thereof in treating the diseases associated with thrombocyte aggregation ICE', wherein P(O)R5R8 is specified in R1 is specified in phenyl; W is specified in a bond, -O-, -NR3-; R2 is specified in alkyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, phenyl, heterocyclyl, or heteroaryl, alkoxycarbonyl alkyl, carboxyalkyl or phenyl alkyl; R3 is specified in hydrogen or alkyl; or R2 and R3 form a ring together with a nitrogen atom; Ra is specified in hydrogen or methyl; R4 is specified in alkoxy; n is from 0 to 3; m is from 0 to 1; V is specified in a bond and phenyl; R5 and R8 are specified in hydroxyl, phenyloxy, benzyloxy, -O-(CHR6)-O-C(=O)-R7, -O-(CHR6)-O-C(=O)-O-R7, -O-(CHR6)-C(=O)-O-R9, -NH-(CHR10)-C(=O)-O-R9, -NH-C(CH3)2-C(=O)-O-R9; q is equal to 2; R6 is specified in hydrogen and alkyl; R7 is specified in alkyl or cycloalkyl; R9 is specified in alkyl; R10 is specified in hydrogen, alkyl, phenyl or benzyl; and R11 is specified in hydrogen, alkyl or alkoxy.
EFFECT: new P2Y12 receptor antagonists are produced.
25 cl, 126 ex, 5 tbl
SUBSTANCE: invention relates to medicine, in particular to ophthalmology and endocrinology, and can be used for treatment of endocrine ophthalmopathy. For this purpose introduced are: galium heel is introduced in dose 10 drops in 50-100 ml of water 3 times per day, for 3 weeks, reneel in dose 1 tablet sublingually 3 times per day for 3 weeks, injections of cerebrum compositum under skin in dose 2.2 ml 2 times per week, with 3-day interval, 5 injections in total, starting from the first day of treatment, injections of coenzyme compositum under skin in dose 2.2 ml 2 times per week, with 3-day interval, 5 injections in total, as well as hirudotherapy 2-3 leeches on temporal area, starting from the first day of treatment, two times per week, 4-6 procedures in total, with 3-day interval, radiotherapy, starting from the first day of treatment, by means of beta-applicators on projection of thickened muscles with radionuclide Ruthenium-106+ Rhodium 106, 5 sessions, 200 cGy each, daily.
EFFECT: method makes it possible to increase efficiency of treatment of endocrine ophthalmopathy due to reduction of edema of retrobulbar tissue and extraocular muscles with the lowest number of side effects and improvement of parameters of blood of thyroid gland hormones.