Drugs for disorders of the cardiovascular system (A61P9)

A   Human necessities(308424)
A61P9                 Drugs for disorders of the cardiovascular system(2552)

Composition including amlodipine and losartan having improved stability // 2628538
FIELD: pharmacology.SUBSTANCE: pharmaceutical composition for cardiovascular disorders prevention and treatment is described. The said composition comprises amlodipine besylate in an amount of 1.7 to 1.72 wt %, potassium losartan in an amount of 12.22 to 12.37 wt %, and propyl gallate in an amount of 0.01 wt %, based on the total weight of the composition. The said composition has the form of a two-layer pill having two separate layers consisting of an amlodipine layer containing amlodipine besylate and propyl gallate and a layer of losartan containing potassium losartan.EFFECT: improved composition stability in combination with simplicity of preparation.6 cl, 21 tbl, 2 dwg, 5 ex

eans for left ventricle diastolic function improvement // 2627842
FIELD: pharmacology.SUBSTANCE: application of 4-[(2-{(2R)-2-((1E,3S)-4-(4-fluorophenyl)-3-hydroxy-1-buten-1-yl]-5-oxo-1-pyrrolidinyl}ethyl)thio]butanoic acid, or a salt thereof, of its clathrate complex with cyclodextrin for preparation of means 1) for treatment of diastolic heart failure and/or symptom alleviation; 2) for heart failure treatment, at which the diastolic function is weakened; 3) for left ventricle diastolic function improvement; 4) for left ventricle expansion improvement; 5) for left ventricle selective diastolic function improvement; 6) for diastolic functional insufficiency treatment or improvement; 7) for diastolic dysfunction treatment or improvement.EFFECT: agent improves diastolic function of the left ventricle itself, without dependence on diuretic influence or vasodilator effect, controls the pathological state of diastolic functional insufficiency and prevents relapse, can prevent dyspnea and death caused by a pathological condition, the agent can alleviate diastolic functional failure for which an effective therapeutic method has not been established.10 cl, 3 dwg, 5 tbl, 2 ex

9-benzyl-2-biphenylimidazo[1,2-a]benzimidazole and pharmaceutically acceptable salts thereof that express properties of destroyers of transversal cross-links of glycosylated proteins // 2627769
FIELD: pharmacology.SUBSTANCE: invention relates to new 9-benzyl-2-biphenylimidazo[1,2-a]benzimidazole (I) and pharmaceutically acceptable salts thereof.EFFECT: imidazobenzimidazole derivatives having the property of destroyers of transversal cross-links of glycosylated proteins.3 cl, 2 dwg, 1 tbl, 1 ex
Gpr40 agonists // 2627703
FIELD: pharmacology.SUBSTANCE: invention relates to a compound of formula (I), wherein ring A is an optionally substituted phenyl group, wherein the optional substituent is fluorine or methoxy; ring B is an optionally substituted phenyl group, wherein the optional substituent is selected from methoxy, 1 or 2 fluorine atoms, -CH2CN, -O-CH2-C3cycloalkyl, isopropoxy; isoxazole (which may be substituted with 1 or 2 methyl groups), -O-CH2-CN and -O-CH2-C(O)OH; X is a bond or -CH2O-; Y is -CH2O-; Z is a bond or -(CR5R6)-; L is -CO2H; R1 is OR7; R2 is a ring, selected from the group consisting of C3-C12 cycloalkyl, C6aryl-condensedC3-C6 cycloalkyl, and optionally substituted C6 aryl, each possible substituent being selected from methyl, fluoro, methoxy, cyano and methanesulfonyl; each R3, R4, R5 and R6 is independently selected from the group consisting of H, CN, OH, CONH2, C1-C12 alkyl, C2-C12 alkynyl, C6 aryl and optionally substituted C1-C18 heteroaryl selected from isoxazole, wherein the isoxazole may be substituted with 1 or 2 methyl groups, or any two of R3, R4, R5 and R6 together with the atoms to which they are attached, can form an optionally substituted C3 cycloalkyl or a double bond between the atoms to which they are attached; R7 is selected from the group consisting of H, optionally substituted C1-C12 alkyl, where possible substituents are selected from 3 fluorine atoms or -N(CH3)2 or phenyl, C2-C12 alkenyl, C3-C12 cycloalkyl and C6 aryl; r is 1; or a pharmaceutically acceptable salt thereof. The compounds of formula (I) of the invention are intended for manufacture of a pharmaceutical composition or a medicament for diabetes treatment.EFFECT: GPR40 activating connections.30 cl, 3 tbl, 124 ex
Polybacterial drug with advantages for health: with antioxidant effect, decreased cholesterol concentration, anti-inflammatory and immuno-modulating effect, and release of bioactive peptides inhibiting angiotensin-converting enzyme // 2627651
FIELD: biotechnology.SUBSTANCE: group of inventions refers to polybacterial probiotic drug including new strains of lactic acid bacteria Lactobacillus gasseri 7/12 NBIMCC No. 8720, Lactobacillus plantarum F12 NBIMCC No. 8722 and Lactobacillus helveticus A1, NBIMCC No. 8721, which has anti-inflammatory immunomodulatory, hypocholesterolemic, antioxidant and antihypertensive activity. The group of inventions also refers to the use of drug as a probiotic agent, as well as an agent which has anti-inflammatory immunomodulatory, hypocholesterolemic, antioxidant and antihypertensive activity.EFFECT: food additives, food and functional products, pharmaceutical preparations that include this drug, have a beneficial effect on the health of people and animals.9 cl, 8 dwg, 15 tbl
4-aryl (hetaril) methyl-substituted 8-cyclopentilamine-5,7-difluor-3,4-dihydro-2h-benzo [1,4] thiazine-1,1-dioxides that hypertensive action // 2627499
FIELD: pharmacology.SUBSTANCE: invention relates to 4-aryl (hetaryl) methyl-substituted 8-cyclopentylamino-5,7-difluoro-3,4-dihydro-2H-benzo [1,4] thiazine-1,1-dioxides 1: .EFFECT: new compounds of formula 1 have been obtained, which can be used as mild hypertensive drugs.1 tbl, 3 ex

Formulations of 2-iminobiotine and use thereof // 2627460
FIELD: pharmaceutics.SUBSTANCE: present invention relates to 2-iminobiotine pharmaceutical aqueous composition, having pH from 3 to 7 and containing 1 mg/ml or more of 2-iminobiotine and from 2.5 to 40 % of substituted beta-cyclodextrin, wherein said substituted beta-cyclodextrin is selected from sulfobutylether-beta-cyclodextrin (SBE-CD) and hydroxypropyl-beta-cyclodextrin.EFFECT: invention provides creation of aqueous solution of 2-iminobiotine with high content of 2-iminobiotine (higher solubility of 2-iminobiotine), which is ensured by introduction of substituted beta-cyclodextrin into disclosed composition or citric acid/citrate buffer to ensure solution pH from 3 to 7.19 cl, 14 ex, 27 tbl, 1 dwg
ethod for correction of lipid peroxidation processes in patients with acute myocardial infarction // 2627458
FIELD: medicine.SUBSTANCE: 30 minutes before recanalization, patients receive 20 ml of Cytoflavin solution diluted in 250 ml of 5% glucose solution intravenously for 30 minutes by drop infusion.EFFECT: invention provides a stabilizing effect on peroxidation processes, increases the antioxidant system activity, providing prevention of reperfusion injury and improving the functional state of the ischemic myocardium.2 tbl, 2 ex
Biaryl- or heterocyclic biaryl-substituted derivatives of cyclohexene as cetp inhibitors // 2627361
FIELD: pharmacology.SUBSTANCE: invention relates to a biaryl or heterocyclic biaryl-substituted cyclohexene derivatives of formula I a stereoisomer thereof or a pharmaceutically acceptable salt thereof, wherein R1 is -H or -C1-C3 alkyl; R2 is -C1-C3alkyl; each of R3, R4, R5 and R6 is independently -H, halogen, -NO2 , -C1-C3alkyl or -OC1-C3alkyl; R7 is -H, -(C=O)OR8 or -C(O)-NR11R12; R8; R8 is -H or -C1-C3alkyl; R11 and R12 are each independently -H or -C1-C3alkyl or can form a 4 to 6-member non-aromatic ring, wherein the non-aromatic ring may contain a N heteroatom and 0 to 1 O heteroatom, and one or more -H in the non-aromatic ring may be replaced by halogen or -OH; each of A1, A2 and A3 is independently N or CR9, where, if A2 or A3 is N, A1 is CR9; R9 is -H, halogen, -C1-C3alkyl or -OC1-C3alkyl; B is N or CR10; R10 is -H, halogen, -OC1-C3alkyl or -(C=O)OR8; provided that one or more H atoms in -C1-C3alkyl or -OC1-C3alkyl can be substituted with -F or -CH3, and if R7 is -H, B is CR10 and R10 is -(C=O)OR8, and if R7 is not -H, R10 not -(C=O)OR8. The invention relates to a pharmaceutical composition having a CETP inhibitory activity comprising, as an active ingredient, a compound of formula I, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. The compounds of the invention are intended to prevent or treat dyslipidemia or diseases associated with dyslipidemia, including angina pectoris, myocardial infarction or arteriosclerosis.EFFECT: biaryl- or heterocyclic biaryl-substituted derivatives of cyclohexene as CETP inhibitors.11 cl, 32 tbl, 172 ex
Bicyclic heterocyclic derivatives, their production and application // 2627269
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of general formula (I) , as well as to a method for their preparation, pharmaceutical compositions based thereon, and their application.EFFECT: new compounds have been obtained that can be used to treat or prevent pathology for which it is necessary to inhibit the mTOR kinase.20 cl, 4 tbl, 30 ex

ethods of production isoquinolinones and solid forms isoquinolinones // 2626883
FIELD: chemistry.SUBSTANCE: invention relates to new polymorphic forms of the compounds of formula (I), having inhibitory action against phosphoinositide 3-kinase (PI3K). The compounds may be used to treat cancer, such as leukemia, lymphoma, inflammatory disease and autoimmune disease. The polymorphic forms of the compound of formula (I) is the polymorphic form C of the hydrate of the compound of formula (I), which has characteristic peaks in the x-ray powder diffraction pattern (XRPD) 2θ=10.4°(±0.2°), 13.3°(±0.2°) and 24.3°(±0.2°); Polymorph A, which has characteristic peaks in the X-ray powder diffraction pattern (XRPD) 2θ=9.6°(±0.2°), 12.2°(±0.2°), and 18.3°(±0.2°); Polymorph B, which has characteristic peaks in the X-ray powder diffraction pattern (XRPD) 2θ=7.9°(±0.2°), 13.4°(±0.2°), and 23.4°(±0.2°); polymorphic form D, which has characteristic peaks in the X-ray powder diffraction pattern (XRPD) 2θ=11.4°(±0.2°), 17.4°(±0.2°), and 22.9°(±0.2°); polymorphic form E, which has characteristic peaks in the X-ray powder diffraction pattern (XRPD) 2θ=6.7°(±0.2°), 9.3°(±0.2°) and 24.4°(±0.2°); Polymorphic form F, which has characteristic peaks in the X-ray powder diffraction pattern (XRPD) 2θ=9.6°(±0.2°), 17.3°(±0.2°), and 24.6°(±0.2°); Polymorphic form G which is the solvate of the tert-butyl methyl ether of the compound of formula (I) and has characteristic peaks in the powder XRPD pattern 2θ=6.7°(±0.2°), 9.5°(±0.2°) and 19.0°(±0.2°); Polymorphic form H, which has characteristic peaks in the X-ray powder diffraction pattern (XRPD) 2θ=8.9°(±0.2°), 9.2°(±0.2°) and 14.1°(±0.2°); Polymorphic Form I, which has characteristic peaks in the X-ray powder diffraction pattern (XRPD) 2θ=9.7°(±0.2°), 19.3°(±0.2°), and 24.5°(±0.2°), and the polymorphic form J, which has characteristic peaks in the X-ray powder diffraction pattern (XRPD) 2θ=9.1°(±0.2°), 17.3°(±0.2°) and 18.3°(±0.2°). The invention also relates to a process of preparing form C. For example, mentioned process comprising (i) exposure of the medium containing water, a composition comprising at least one polymorphic form, not a form of a compound of formula (I), for a period time sufficient for the transformation, preferably for 18-24 hours, at least 50% of the total amount of the polymorphic form (s) a non-form C; and (ii) recovering mentioned polymorph form C.EFFECT: high effectiveness of compounds.84 cl, 31 dwg, 16 tbl, 42 ex
Preparation for treatment of bony lumps, headaches and heartaches // 2626844
FIELD: pharmacology.SUBSTANCE: invention is a preparation for application to the skin surface for bony lumps, headaches and heartaches treatment, consisting of 5 ml of turpentine, 50 ml of 40% formalin, characterized by additional content of 96% ethyl alcohol solution in an amount of 45 ml. The proportions of constituents are given for 100 ml of the preparation.EFFECT: invention provides resorption of bony lumps, disappearance of pain in the heart and head areas, and also allows to do without surgical installation of plates for vertebrae fixation while infringing the nerve fibers as a result of their squeezing.5 ex
Fluorated 4-furfuryl-3,4-dihydro-2h-benzo[1,4]thiazine-1,1-dioxides with high arrythmic activity // 2626239
FIELD: pharmacology.SUBSTANCE: invention relates to new fluorinated 4-furyl-3,4-dihydro-2H-benzo[1,4]thiazine-1,1-dioxides of general formula .EFFECT: new compounds of formula 1 are obtained, which have high antiarrhythmic activity.1 tbl, 5 ex
Use of 3-n-butyl ketone isoindoline in production of drugs for prevention and treatment of cerebral infarction // 2625797
FIELD: pharmacology.SUBSTANCE: invention relates to the use of 3-n-butyl ketone isoindolin of the formula I for the preparation of drugs for the prevention and treatment of cerebral infarction.EFFECT: compound may be used in various dosage forms and gives great possibilities of clinical application.7 cl, 5 dwg, 6 ex
Derivatives of 1,2,4-triazine-4-amine // 2625791
FIELD: pharmacology.SUBSTANCE: compounds of Iyd formula possess an inhibitory activity against A1 receptor or A2a receptor. In formula Iyd B represents "CyBB". "CyBB" represents phenyl optionally having one or more substituents R4c. R4b, R4b' and R4c are, in each case independently, a halogen atom. CN. C1-8 alkyl, which optionally bears one or more substituents selected from halogen atoms, OR5a; C3-8 cycloalkyl; Heta; OR8; N (R9f) (R9g); =O; rr2 is 0-1; and ss tt are, in each case independently, 0 or 1, provided that ss and tt can not simultaneously be equal to 0. L1 and L2 are both single bonds; R8 represents, in each case independently, C1-8 alkyl, which optionally bears one or more substituents selected from halogen atoms. Heta represents, independently in each case, 3-6-membered fully saturated heterocyclic ring which contains one or two heteroatoms selected from O and N. R5a, R9f, R9g are H in each case independently; C1-10 alkyl. The invention also relates to individual compounds, to use of a compound, a pharmaceutical composition and a process for preparing a compound of Iyd formula.EFFECT: new compounds with an inhibitory activity against A1 receptor or A2a receptor.12 cl, 7 ex

eans for treating ischemia of vascular brains // 2625740
FIELD: pharmacology.SUBSTANCE: invention concerns the use of 5,6,8-trihydroxy-2,3-diglutathionyl-7-ethyl-1,4-naphthoquinone as an agent for the treatment of cerebral ischemia in acute cerebrovascular disorders. The invention results in a faster reduction of the edema zone in comparison with analogues.EFFECT: expansion of the arsenal of funds intended for the treatment of cerebral ischemia in acute disorders of cerebral circulation, low toxicity, good solubility in physiological saline and storage time.8 dwg, 5 tbl
Pharmaceutical injection form of hydrophilic conjugate of hydroxyethylamylum and 2,6-diisobornyl-4-methylphenol, method for its production and applications for cardiovascular diseases treatment // 2625039
FIELD: pharmacology.SUBSTANCE: pharmaceutical injection form of hydrophilic conjugate of hydroxyethylamylum and 2,6-diisobornyl-4-methylphenol for cardiovascular diseases treatment contains a therapeutically effective amount of O-(4-hydroxy-3,5-di(1,7,7-trimethylbicyclo[2.2.1]hept-exo-2-yl)benzyl)oxy)ethyl)-O-(2-hydroxyethyl)-(1,4)-α-D-glucan (Dibornol-HEC) as an active ingredient. Sodium chloride, Tween 80, ascorbic acid, water for injection or saline in the amounts indicated in the claims are used as auxiliary components. In the method for pharmaceutical injection form preparation, the Dibornol-HEC substance is added to an aqueous solution of Tween 80 surfactant and mixed until the substance is dissolved completely and a clear solution is obtained, the water is distilled off under reduced pressure, ascorbic acid, sodium chloride, saline (water for injection) are added to the dry residue and mixed, the solution is adjusted to a concentration of 4.5-7.5% by the active Dibornol-HEC substance with saline (water for injection) and centrifuged, if necessary, the solution is filtered, the resulting drug solution is poured into glass vials or ampoules, which are sealed and packaged.EFFECT: pharmaceutical injection form of the invention is stable.2 cl, 1 tbl, 15 ex
ethod of correction of endothelial dysfunction at progressive current of objective atherosclerosis of vessel limbs // 2624870
FIELD: medicine.SUBSTANCE: against the background of basic therapy with drugs that improve microcirculation, antispasmodics, antiplatelet agents and statins, additionally intravenously injected ozonized saline solution once a day in a volume of 400 ml with an ozone concentration of 2-4 mg/l. Then, not earlier than 4-6 hours, Vasaprostan® is administered - 60 mcg of alprostadil dissolved in 250 ml of a 0.9% solution of sodium chloride or Ringer's solution, with an infusion rate of 80 ml/h, with a course of 10 days.EFFECT: application of the invention allows stabilizing the progression of the atherosclerotic process, increasing the walking distance and reducing the risk of developing critical ischemia.1 tbl, 2 ex

Pharmaceutical compositions containing epa and cardiovascular agents and their application methods // 2624506
FIELD: pharmacology.SUBSTANCE: invention is a method for the treatment of mixed dyslipidemia in a subject receiving treatment with statins. Herewith the method includes administration of 4 capsules per day to the subject in the fasted state. Each capsule contains of 900 mg, 925 mg, 950 mg, 975 mg or 1 g ethyl-EPA to reduce triglycerides and LDL-C in a subject relative to subjects with mixed dyslipidemia who receive statins without ethyl-EPA.EFFECT: reduced level of triglycerides and LDL-C levels in subjects with mixed dyslipidemia of different intensity.13 cl, 1 ex, 4 dwg

Application of vanadium compounds for maintaining normoglycemia in mammals // 2624495
FIELD: pharmacology.SUBSTANCE: pharmaceutical composition is proposed comprising bis-(maltolato) oxovanadium (IV) to maintain normoglycemia in a critically ill patient, suffering from acute stress representing an acute renal failure or acute coronary failure or both.EFFECT: increased microvascular oxygenation and increased effective oxygen uptake in the kidneys of the mentioned patient.14 cl, 7 dwg, 1 tbl
Bis(metoxybenzylaminoalkyl)amines with cardiotropic activity // 2624438
FIELD: pharmacology.SUBSTANCE: invention relates to new bis(methoxybenzylaminoalkyl)amines of general formula (I) and their physiologically acceptable salts with cardiotropic activity. Due to their acute toxicity (LD50), compounds belong to classes III and IV of toxicity. In the general formula (I), R1, R2, R3, R4 may be two or three hydrogens, or one or two methoxy groups, n and m may be the same and have the values 2 or 3 or different and have the values n=2 and m=3. As the pharmaceutically acceptable salts of bis(methoxybenzylaminoalkyl)amines of general formula I, their trihydrochlorides of general formula II (I⋅3HCl) are preferred. Most preferred are trihydrochlorides selected from trihydrochloride N1-(2,5-dimethoxybenzyl)-N2-{2-[(2,5-dimethoxybenzyl)amino]ethyl}-1,2-ethanediamine (IIc), trihydrochloride N1-(2,3,4-trimethoxybenzyl)-N2-{2-[(2,3,4-trimethoxybenzyl)amino]ethyl}-1,2-ethanediamine (IId) and trihydrochloride N1-(2,4-dimethoxybenzyl)-N3-{3-[(2,4-dimethoxybenzyl)amino]-propyl}-1,3-propanediamine (IIf).EFFECT: compounds exhibit anti-ischemic and antiarrhythmic, in particular antifibrillatory, action.14 cl, 5 tbl, 14 ex
ethod for obtaining means with anti-arithmal action // 2624240
FIELD: pharmacology.SUBSTANCE: this method provides allocation of a technical amount of alkaloids - a technical product from Aconitum (foxbane) plants of Ranunculaceae (buttercup) family and its purification, when the technical product is dissolved in one of the monohydric aliphatic saturated alcohols from the group: methanol, ethanol. Then, alcohol from the group of monohydric aliphatic saturated alcohols with a carbon number of 3 to 5 in an amount of 4-20 vol. % of the resulting solution is added to the resulting solution, the solution is evaporated until the alcohol (methanol, ethanol) is completely removed, and the final crystallisation of the target product in an alcohol from the group of monohydric aliphatic saturated alcohols with a carbon number of 3 to 5 is performed, followed by filtration, washing and drying to obtain the desired purified product.EFFECT: increased direct yield of the finished product, obtaining of a product of higher quality compared to known analogues.9 cl, 6 ex

ethods and compositions for modeling expression of apolipoprotein (a) // 2624028
FIELD: biotechnology.SUBSTANCE: obtained modified antisense compounds are able to specifically inhibit the expression of the nucleic acid apo (a). The invention may be used as a medicament for treating, preventing or slowing the progression of disease associated with increased apo (a) or Lp (a), at an individual in need thereof.EFFECT: reduced expression of apolipoprotein mRNA and protein in an animal, and can be used in medicine.23 cl, 65 tbl, 13 ex
Pharmaceutical composition for hyperlipidemia treatment // 2623876
FIELD: pharmacology.SUBSTANCE: pharmaceutical composition for hyperlipidemia treatment comprises a mixture of a glycyrrhizic derivative selected from glycyrrhizic acid and a pharmaceutically acceptable salt thereof, and a hypolipidemic drug-statin selected from atorvastatin, lovastatin, rosuvastatin, simvastatin, pravastatin, pitavastatin, fluvastatin and pharmaceutically acceptable salts or mixtures thereof, and auxiliary substances.EFFECT: increased efficiency of the composition application.24 cl, 36 tbl, 2 ex
Short-term acting dihydropyridines (clevidipine) for recovery after stroke // 2623039
FIELD: pharmacy.SUBSTANCE: invention relates to methods for post-stroke recovery and blood pressure reduction for patient with stroke, who is in need of such treatment, comprising introduction of an effective amount of a pharmaceutical composition containing a short-term acting dihydropyridine compound, represented by clevidipine or a pharmaceutically acceptable salt or ester thereof. The pharmaceutical composition is an emulsion comprising a lipid and an emulsifier. Methods for pharmaceutical compositions preparations are also described.EFFECT: optimal ratio of efficiency, accuracy and safety of rapid blood pressure reduction for stroke patients, with minimal neurological impairment.32 cl

Selective and reversible ubiquitin-specific protease 7 inhibitor // 2622640
FIELD: pharmacology.SUBSTANCE: viral infections and diseases are selected from viral infections of Herpes simplex-1 or -2, hepatitis A, hepatitis C, SARS of coronavirus infection and disease, Epstein-Barr virus, rhinovirus infections and diseases, adenovirus infections and diseases, poliomyelitis. In the formula each identical or different R1 is selected from the group consisting of halogen, linear or branched (C1-C6)alkyl, OR; L1 is a linear or branched (C1-C6)alkylene; Q is 0, 1, 2, 3 or 4; X' is CR7; R7 is OR; N is 0, 1 or 2; P is 1, 2 or 3; R3, R4, R8' and R8 each represents H; A is -C (O)-; L2 is linear or branched (C1-C6) alkylene, optionally interrupted by at least one O; R6 is selected from the group consisting of aryl, heteroaryl, cycloalkyl, H, wherein aryl, heteroaryl, cycloalkyl is mono- or polycyclic and is optionally substituted by halogen, OR; each R, identical or different, is independently selected from H, linear or branched (C1-C6)alkyl. At that, "aryl" means an aromatic monocyclic hydrocarbon ring system of 6 carbon atoms, "cycloalkyl" means a non-aromatic, monocyclic, hydrocarbon ring of 3-10 carbon atoms; "heteroaryl" means a 5-membered aromatic mono-heterocyclic ring. The invention also relates to versions of the for preparation of compounds.EFFECT: compounds can be used to prepare a drug for treatment or prevention of cancer and metastases, viral infections and diseases, or viral infectivity, or latency mediated by ubiquitin-specific proteases activity.19 cl, 6 dwg, 4 tbl, 14 ex
Derivatives of quinazoline-4 (3h)-one, with neuro- and cardioprotective activity // 2622638
FIELD: pharmacology.SUBSTANCE: invention relates to novel quinazoline-4(3H)-one derivatives of the general formula (I) which possess neuroprotective and cardioprotective activity and can be widely used in treatment of diseases of the central nervous and cardiovascular system of vascular, traumatic, toxic and hypoxic origin. In formula (I) , (I)R1 = H or CH3; R2 = H, Cl or Br; R3 = H or Br; R4 = H or CH3. On experimental models in vivo, the compounds of formula (I), having the ability to protect the brain and myocardium under the conditions of circulatory insufficiency, surpass the drugs of various pharmacological groups, such as verapamil, ivabradine, cavinton, mexidol, piracetam, in a range of useful properties.EFFECT: increased efficiency of treatment.13 tbl, 4 ex

Derivatives of sitaxenthan // 2622386
FIELD: pharmacology.SUBSTANCE: invention relates to N-(4-chloro-3-methyl-1.2-oxazol-5-yl)-2-[2-(6-methyl-1.3-dihydro-2-benzofuran-5-yl)acetyl]thiophene-3-sulfonamide or a pharmacologically acceptable salt thereof. The compound of the invention is intended as an endothelin receptor antagonist or therapeutic or prophylactic agent for the treatment of pulmonary arterial hypertension.EFFECT: compound that maintains the main therapeutic effect of sitaxentan and has an improved CYP inhibitory effect.3 cl, 4 tbl, 3 dwg, 3 ex
Inhibitors of nonprilyzine // 2622288
FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula , wherein R1 is selected from -OR7 and -NR8R9; R2 is H; X is -C1-9heteroaryl, selected from pyrazole, imidazole, triazole, benzotriazole, furan, tetrazole, pyrazine, thiophene, oxazole, isoxazole, thiazole, oxadiazole, pyridazine, pyridine, pyrimidine, benzoxazole, pyridylimidazole and pyridyltriazole; R3 is absent or is selected from H; Halogen; -C0-5alkylene-OH; -NH2; -C1-6alkyl; -CF3; -C3-7cycloalkyl; -C0-2alkylene-O-C1-6alkyl; -C(O)R20; -C0-1alkylene-COOR21; -C (O) NR22R23; -NHC(O)R24; =O; -NO2; -C(CH3) =N(OH); Phenyl optionally substituted with one or two groups independently selected from halogen, -OH, -CF3, -OCH3, -NHC(O)CH3 and phenyl; Naphthalenyl; Pyridinyl; Pyrazinyl; Pyrazolyl optionally substituted with methyl; Thiophenyl, optionally substituted by methyl or halogen; Furanyl; and -CH2-morpholinyl; and R3, when present, is attached to a carbon atom; R4 is absent or is selected from H; -HE; -C1-6alkyl; -C1-2alkylene-COOR35; -OCH2 O(O)CH (R36)NH2; -OCH2O(O)CH3; -CH2CH(OH)CH2OH; and phenyl or benzyl optionally substituted with 1 to 3 groups selected from halogen, -COOR35, -OCH3, -OCF3 and -SCF3; and R4, when present, is attached to a carbon or nitrogen atom; or R3 and R4 are taken together to form -phenylene-O- (CH2) 1-3- or -phenylene-O-CH2-CHOH-CH2-; A is 0 or 1; R5 is halogen; B is 0 or an integer of 1 to 3; Each R6 is independently selected from halogen, -OH, -CH3 and -OCH3; R7 is selected from H, -C1-8alkyl, -[(CH2)2O]1-3CH3, -C1-6alkylene-OC(O)R10, -C0-6alkylenemorpholinyl, -C1-6alkylene-SO2-C1-6alkyl and the structure of formula (a); R10 is -O-C3-7cycloalkyl; and R32 is -C1-6alkyl; R8 and R9 are H; R20, R21 and R35 are independently selected from H and -C1-6alkyl; R22 and R23 are independently selected from H, -C1-6alkyl, -CH2COOH, -(CH2)2OH, -(CH2)2OCH3, - (CH2)2SO2NH2, -(CH2)2N(CH3)2, -C0-1alkylene-C3-7-cycloalkyl and -(CH2)2-imidazolyl; or R22 and R23 are taken together to form a ring; R24 is selected from -C1-6alkyl; -C0-1alkylene-O-C1-6alkyl; Phenyl optionally substituted by halogen or -OCH3; and pyridinyl; and R36 is -CH (CH3) 2; and wherein the methylene linker on the biphenyl is optionally substituted with one or two -C1-6 alkyl groups; or a pharmaceutically acceptable salt thereof. Compounds of formula (I) are prepared by combining a compound of formula with a compound of formula 2 to provide a compound of formula I; Where P1 is also H. Also, the invention relates to an intermediate of formula 1, wherein P1 is H. The compounds of formula (I) are intended for the preparation of a medicament or pharmaceutical composition having inhibitory activity against non-prolamin (NEP). (a).EFFECT: compounds that have a non-lysine inhibitory enzyme activity.28 cl, 61 tbl, 25 ex

Crystalline form of compound used as a mineralocorticoid receptor antagonist and the method of its production // 2622105
FIELD: chemistry.SUBSTANCE: invention relates to crystalline forms I and II of compound 2-chloro-4-[(3S,3aR)-3-cyclopentyl-7-(4-hydroxy-1-carbonyl)-3,3a, 4.5-tetrahydro-2H-pyrazolo[3.4-f]quinolin-2-yl]benzonitrile of formula (I), used as a mineralocorticoid receptor antagonist. Crystalline forms have characteristic peaks of powder X-ray diffraction pattern specified in the claims. The invention also relates to processes for preparing crystalline forms I and II and the use of the obtained crystal forms in the manufacture of medicaments for the treatment and/or prevention of kidney damage or cardiovascular diseases.EFFECT: obtained crystalline form the compound of formula amorphous form of its superior stability, not only at high temperature and humidity, and light conditions.16 cl, 4 dwg, 4 tbl, 10 ex
ethod for selection of pulsaturization therapy therapy of stable stenocardium in persons of elderly and senior age // 2621304
FIELD: medicine.SUBSTANCE: invention is intended for selection of an individual regimen of antianginal pulsaturization therapy in patients with IHD of elderly and senior age. Monotherapy with bisoprolol 10 mg/day or a combination of bisoprol 5 mg/day with ivabradine 10 mg/day is selected by evaluating the results of heart rate variability, quality of life, Hamiltonian scores and patient adherence based on calculation and comparison of prognostic factors to achieve complete clinical effect of treatment stable stenocardia.EFFECT: method allows to optimize the timing of treatment selection and achieve a clinical effect with a minimal risk of side effects of therapy.2 tbl,1 ex

Pharmaceutical composition for extended trimetazidine release // 2621128
FIELD: medicine, pharmacy.SUBSTANCE: invention relates to pharmacy. The composition comprises an inner phase and an outer layer. The inner layer is composed of coated trimetazidine dihydrochloride in a neutral nucleus and hydroxypropylmethylcellulose. The outer layer comprises ethyl cellulose, acetyl tributyl citrate, and talc. These components are contained in the following amounts: trimetazidine dihydrochloride - 80 mg, neutral core - 36.677 mg hydroxypropyl methylcellulose - 6.40 mg, acetyl tributyl citrate - 1.2 mg ethylcellulose - 8 mg, talc - 12 mg. The invention provides a composition with prolonged trimetazidine release for over 24 hours with therapeutic concentration levels in blood maintained for 24 hours.EFFECT: pharmaceutical composition is used for prolonged trimetazidine release.3 cl, 5 dwg, 3 tbl, 3 ex
eans for ischemia treatment, method for its production and method for ischemia treatment (versions) // 2620163
FIELD: pharmacology.SUBSTANCE: invention is a means for ischemia treatment containing a complex of ethyl 2-(2-(1-methylguanidino)acetamido)acetate salt as an active principle, as well as a method for the preparation of the ischemia treatment means and a method for ischemia treatment. It is proposed to create versions of the ischemia treatment means representing a complex of ethyl-2-(2-(1-methylguanidino)acetamido)acetate salt with sugars, fibrinolytic enzymes and mannitol.EFFECT: means with increased efficiency and stability.28 cl, 28 tbl, 25 ex

Crystalline solvates of hydrochloride 6-(piperidin-4-yloxy)-2h-isoquinolin-1-one // 2619129
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry, in particular to crystalline dihydrate 6-(piperidin-4-yloxy)-2H-isoquinolin-1-one of formula and a solid pharmaceutical composition thereof.EFFECT: obtained crystalline hydrochloride dihydrate, having better stability and hygroscopicity, which is preferable in obtaining the medicinal product based on it.16 cl, 14 dwg, 1 tbl

Form iv of ivabradine hydrochloride // 2619121
FIELD: medicine, pharmacy.SUBSTANCE: invention refers to ivabradine hydrochloride form IV with powder diffraction containing the following peaks expressed in 2 theta (±0.2) degrees: 8.74, 15.55, 17.17, 19.89 and 24.29, at that, the X-ray diffraction was measured using CuK-radiationα, as well as to pharmaceutical compositions based thereon, to methods for its preparation and application as a therapeutically active ingredient.EFFECT: invention provides a new thermodynamically stable crystalline form of ivabradine hydrochloride with constant physical properties.31 cl, 4 dwg, 2 tbl, 32 ex

Phenyl derivatives // 2619105
FIELD: chemistry.SUBSTANCE: invention relates to new compounds of general formula containing two cyclic groups, especially where M1 - Ring 1 and M2 - Ring 2, each independently represents a phenoxy group. The compounds have high antagonistic activity against human S1P2.EFFECT: invention due to its properties can be used as a therapeutic agent for the treatment of S1P2-mediated diseases such as diseases, resulting from vasoconstriction, fibrosis and respiratory diseases.8 cl, 6 dwg, 5 tbl, 45 ex
ethod for arterial bypass spasms prevention and reliefe during coronary bypass surgery // 2618933
FIELD: medicine.SUBSTANCE: for prevention and relief of spasm of the internal mammary artery or the radial artery during preparation for use as a bypass during coronary bypass, arterial vessel is isolated, and its distal end is crossed. The proposed solution is intriduced into the vessel lumen via the soft catheter and the vessel is clipped so that the solution remained in the lumen of the taken vessel, and the other end of artery is not clipped. The proposed solution comprises 0.1% solution of nitroglycerin - 20.0 ml; 0.25% solution of verapamil hydrochloride - 4.0 ml; 4% solution of sodium hydrogencarbonate - 10.0 ml; Heparin - 500 units; saline - up to 200.0 ml. Then the arterial vessel is treated from the outside with the same solution along the entire length by the G21 needle syringe so that it is foamed on the artery surface. After syringe processing, the artery is wrapped in cloth soaked liberally in the proposed solution and it is left in the bed until it is required to form a bypass.EFFECT: method provides effective prevention and removal of spasm of arterial bypasses in the absence of intima damage and vascular occlusion.

Pcsk9 antagonists // 2618869
FIELD: medicine.SUBSTANCE: present invention relates to medicine and biotechnology. Application of aqueous composition for preparing drug for reducing blood cholesterol and/or levels of low-density lipoproteins (LDL) in blood and/or reduction of disease incidence or correcting abnormal cholesterol and/or levels of lipoproteins is proposed, caused by disturbed cholesterol metabolism and/or lipoproteins, including hypercholesteremia, dyslipidemia, atherosclerosis, hyperlipidaemia and cardiovascular disease, where said composition contains from approximately 1 mg/ml to approximately 200 mg/ml of antibody-antagonist, which specifically binds with proprotein convertase of subtilisin-kexin type 9 PCSK9; from approximately 1 mm to approximately 100 mm of histidine buffer; from approximately 0.01 mg/ml to approximately 10 mg/ml of polysorbate 80; from approximately 100 mm to nearly 400 mm of trehalose; and from 0.01 mm to approximately 1.0 mm of EDTA disodium dihydrate. Antibody in above composition effectively reduces LDL-cholesterol levels.EFFECT: in this regard present invention can find further application in therapy of diseases associated with elevated levels of cholesterol-LDL.6 cl, 24 dwg, 9 tbl, 9 ex

N-piperidin-3-yl-benzamide derivatives for cardiovascular diseases treatment // 2618628
FIELD: pharmacology.SUBSTANCE: invention relates to substituted amide compounds of formula pharmaceutical compositions containing such compounds and application of such compounds for lowering plasma lipid levels, such as low density lipoprotein cholesterol (LDL-cholesterol) and triglycerides, and thus, for treatment of diseases exacerbated by high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases in mammals, including humans.EFFECT: increased efficiency of compounds application.42 cl, 10 dwg, 55 ex
ethod for skeletal muscle experimental ischemia pharmacological correction using vardenafil and pentoxifylline in combined therapy // 2618622
FIELD: medicine.SUBSTANCE: for skeletal muscle ischemia correction on the background of skeletal muscle ischemia simulation, its correction is performed by daily intragastric administration of a combination of vardenafil at a dose of 0.09 mg kg and pentoxifylline at a dose of 30 mg/kg 1 time a day, for 7 days.EFFECT: method provides good rheological effect in the ischemia hearth at lower drugs doses and safety of their use in terms of side effects of treatment.1 tbl, 1 ex
ethod for skeletal muscle experimental ischemia pharmacological correction using sildenafil and pentoxifylline in combined therapy // 2618621
FIELD: medicine.SUBSTANCE: for skeletal muscle ischemia correction on the background of skeletal muscle ischemia simulation, its correction is performed by daily intragastric administration of a combination of sildenafil at a dose of 0.22 mg kg and pentoxifylline at a dose of 30 mg/kg 1 time a day, for 7 days.EFFECT: method provides good rheological effect in the ischemia area at lower drugs doses and safety of their use.1 ex, 1 tbl
ethod for skeletal muscle experimental ischemia pharmacological correction using tadalafil and pentoxifylline in combined therapy // 2618620
FIELD: medicine.SUBSTANCE: for skeletal muscle ischemia correction on the background of skeletal muscle ischemia simulation, its correction is performed by daily intragastric administration of a combination of tadalafil at a dose of 0.09 mg kg and pentoxifylline at a dose of 30 mg/kg 1 time a day, for 7 days.EFFECT: method provides good rheological effect in the ischemia hearth at lower drugs doses and safety of their use in terms of side effects.1 tbl
Oral pharmaceutical composition of diuretics and ace inhibitor in micronized form, drug and its application // 2618471
FIELD: medicine, pharmacy.SUBSTANCE: invention refers to medicine, namely to pharmacy. The pharmaceutical composition contains active ingredients - ramipril (angiotensin-converting enzyme (ACE) inhibitor) and indapamide (sulfonamide diuretic) or pharmaceutically acceptable salts thereof. The active ingredients are in micronized form with average particle size less than 50 microns. The pharmaceutical composition comprises lactose monohydrate, colloidal silicon dioxide and calcium stearate as auxiliary substances. The composition provides a dissolution nature such that at least 80% of the ramipril is released within 45 minutes and at least 80% of indapamide is released within 45 minutes. A hypotensive-effect drug which contains 0.5 - 2.5 mg of indapamide and 1-20 mg of ramipiril is also described. Application of a combined agent containing indapamide and ramipril as a means with cerebral and organ protection properties is also described.EFFECT: invention allows expansion of the range of domestic drugs with hypotensive effect, with the required characteristics and a shelf life of 5 years.4 cl, 12 dwg, 16 tbl
Substituted derivatives of 3-thiazolaminepropionic acid and their use as pharmaceuticals // 2617843
FIELD: chemistry.SUBSTANCE: invention relates to a compound of formulas Ia and Ib , in any of its stereoisomeric form or its physiologically acceptable salt, where G R71-O-C(O)-; R1 represents hydrogen; R2 represents hydrogen; R10 represents R11; R11 represents Ar; R30 is selected from the group including a (C3-C7)-cycloalkyl and R32-CuH2u-, where u means an integer chosen from the series containing 0, 1, 2 and 3; R32 represents a phenyl, optionally substituted by one or more identical or different substituents selected from the group comprising a halogen, a (C1-C6)-alkyl, R33 and (C1-C6)- alkyl-O-; R33 is a phenyl optionally substituted by one substitute selected from a halogen; R40 is selected from the group consisting of hydrogen and (C1-C4)-alkyl, or R30 and R40 together represent (CH2)x, where x is an integer selected from the group comprising 2, 3, 4 and 5; R50 is hydrogen; R60 is hydrogen; R71 is hydrogen; Ar, independently of each other Ar group, is selected from the group comprisng a phenyl and an aromatic 5-membered or 6-membered monocyclic heterocycle containing one or two heteroatoms selected from nitrogen and attached via a ring carbon atom, where the phenyl and the heterocycle all are optionally substituted by one or more identical or different substituents selected from the group comprising a halogen, a (C1-C6)-alkyl, (C1-C6) alkyl-O- and CF3; where all the alkyl substituents, independently from each other and independently of any other substituents, are optionally substituted by one or more fluorine atoms. The invention also relates to obtaining the compound of formulas Ia and Ib, or a physiologically acceptable salt thereof, that is prepared by reacting a compound of formula IIa or IIb with the compound. The compound of formulas Ia and Ib or its physiologically acceptable salt is intended for use as a pharmaceutical agent having the inhibitory activity against cathepsin A.EFFECT: substituted derivatives of the 3-thiazoleaminepropionic acid as protease inhibitors of cathepsin A.7 cl, 1 tbl
5-bromonicotinic acid derivatives with anti-arrhythmic activity // 2617428
FIELD: pharmacy.SUBSTANCE: invention relates to 5-bromonicotinic acid derivatives: , where R1 is hydrogen; R2 is 4-methoxy-6-methyl-1,3,5-triazile-2, or a hydrogen proton or a 2-methyl-1,2,4-triazolyl-1. The compounds can be used in clinical practice for cardiac rhythm correction.EFFECT: creation of a new compound with anti-arrhythmic activity.2 tbl

Pyridone and aza-pyridone compounds and methods of use // 2617405
FIELD: chemistry.SUBSTANCE: invention relates to a compound selected from formula I, or its stereoisomers, or pharmaceutically acceptable salts thereof, where R1 is optionally substituted C1-C3 alkyl; R2, R3 and R4 are independently selected from H, F, Cl; R5 is selected from (i) optionally substituted C6-C20 aryl, selected from phenyl; (ii) optionally substituted C5-C20 heteroaryl, selected from pyrazolyl, pyridinyl, pyrimidinyl, tetrahydroisoquinolinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl, 6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazinyl, 4,6,7-trihydropyrazolo[3,2-c][1,4]oxazinyl, 5,6,7,8-tetrahydro-1,6-naphthyridinyl, 2,3-dihydro-1H-isoindolyl, 4,5,6,7-tetrahydrothiazolo[5,4-c]pyridinyl; (iii) optionally substituted -(C6-C20 aryl)-(C3-C20 heterocyclyl), where heterocyclyl is selected from azetidinyl, piperidinyl, morpholino, piperazinyl; (iv) optionally substituted -(C5-C20 heteroaryl)-(C3-C20 heterocyclyl), where heteroaryl is selected from pyridinyl and pyridazinyl and heterocyclyl is selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, 1,4-diazepanyl, 2,6-diazaspiro[3.3]heptanyl, 7,9-diazabicyclo[3.3.1]nonanyl, hexahydropyrrolo[3,4-c]pyrrolyl, morpholino; (v) optionally substituted -(C5-C20 heteroaryl)-(C1-C6 alkyl), where heteroaryl is selected from pirazolyl and pyridinyl; or (vi) optionally substituted -(C5-C20 heteroaryl)-C(=O)-(C3-C20 heterocyclyl), selected from (pyridinyl)-C(=O)-(morpholino); R6 represents H or C1-C3 alkyl; Y1 and Y2 are independently selected from CR6 and N; where C1-C3 alkyl, C3-C20 heterocyclyl, C6-C20 aryl and C5-C20 heteroaryl optionally substituted with one to three groups, independently selected from D, F, Cl, Br, I, -CH3, -CH2CH3, -CH2CH(CH3)2, -CH2OH, -CH2CH2OH, -C(CH3)2OH, -CH2F, -OC(O)CH3, -COCH3, -NHCH3, -N(CH3)2, =O, -OH, -OCH3, -OCH2CH2N(CH3)2, -OP(O)(OH)2, -CH2OCH3, cyclopropyl, azetidinyl, 1-(methylazetidin-3-yl)oxy, N-methyl-N-oxetan-3-ylamino, azetidin-1-ylmethyl, oxetanyl and morpholino; where group (a), formed Z1, Z2, Z3, Z4, Z5, X and NC(O), forms structure, given in claim, and wherein wavy line indicates bonding point. Invention relates to a pharmaceutical composition for treating a condition, mediated by Bruton's tyrosine kinase, containing a compound of formula (I) and a pharmaceutically acceptable carrier, lubricant, a diluent or filler. Compounds of formula (I) are intended for use as a drug for treating cancer, mediated by Bruton's tyrosine kinase.EFFECT: pyridone and aza-pyridone compounds for treating disorders mediated by Bruton's tyrosine kinase (Btk).20 cl, 9 dwg, 4 tbl, 907 ex (а)
Combined preparation of lercanidipine and atorvastatin // 2617048
FIELD: medicine.SUBSTANCE: group of inventions relates to medicine and pharmacy. Combined preparation of lercanidipine hydrochloride and calcium atorvastatin is disclosed for treating hypertension accompanied by hyperlipidemia, which contains single dose of 5–20 mg of lercanidipine hydrochloride and 10–80 mg of atorvastatin calcium, wherein weight ratio of lercanidipine hydrochloride to atorvastatin calcium is 1:2–4, and method of producing coated tablet containing them.EFFECT: technical result is combined preparation of lercanidipine and calcium atorvastatin according to this invention has higher efficiency at lower dose as compared to combined introduction of tablets with respect to considerable reduction of hypertension and reducing level of lipids; it is characterized by low therapeutic dose and reduction of number of undesired effects, as well as good tolerance and compliance with drug therapy regimen of patients.8 cl, 7 tbl
Preoperative preparation of patient with pheochromocytoma // 2616896
FIELD: medicine.SUBSTANCE: prior to operation, doxazosin is administered orally at the initial daily dose of 2 mg daily with subsequent daily dose increasing by 2-4 mg to normalize the blood pressure. The maximum daily dose of doxazosin is 16 mg. Daily intake of individualized therapeutic dose is continued until normalization of rheovasography readings - total peripheral vascular resistance index and photopletismography amplitude.EFFECT: method allows to stabilise hemodynamics for this patient group.2 ex
Pharmaceutical composition for hyperlipidemia prevention or treatment // 2616522
FIELD: pharmacology.SUBSTANCE: pharmaceutical composition according to invention contains (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-({2-[4-fluoro-2-methoxy-5-(propan-2-yl)phenyl]-5-(trifluoromethyl)phenyl}methyl)-4-methyl-1,3-oxazolidin-2-one or a pharmaceutically acceptable salt thereof in combination with olmesartan or a salt thereof or olmesartan medoxomil or a salt thereof.EFFECT: use of inventions allows to significantly reduce the concentration of triglycerides and to increase HDL-cholesterol in blood due to the synergistic effect of the combination.11 cl, 5 tbl, 2 ex

Pharmaceutical composition containing olmesartan medoxomil and rosuvastatin or its salt // 2616516
FIELD: pharmacy.SUBSTANCE: invention provides a pharmaceutical composition which is a single-dose dosage form comprising a compartment containing olmesartan medoxomil and a compartment comprising rosuvastatin or its salt, wherein the said compartments are formed in the isolated form. The compartment containing olmesartan medoxomil comprises from 7.5 to 65 wt % of hydroxypropylcellulose with a low degree of substitution. The compartment comprising rosuvastatin or its salt includes one or more disintegrants selected from the group consisting of crospovidone, hydroxypropyl cellulose with a low degree of substitution, croscarmellose sodium and carboxymethylcellulose calcium. The disintegrant in the said compartment with rosuvastatin is present in the amount of from 2 to 20 wt %. The pharmaceutical composition is a bilayer tablet or a capsule containing granules. The pharmaceutical composition of the present invention solves the problem of slowing down the absorption associated with drug-drug interactions.EFFECT: combination drug of the present invention is bioequivalent to mono-preparation of each of the said drugs.6 cl, 6 dwg, 16 tbl, 9 ex
 
2551132.
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