Method for hypoestrogen-induced endothelial dysfunction correction with lozartan in complex with mixed solutions of homoeopathic dilutions of polyclonal rabbit c12, c30, c200 antibodies to human endothelial nitrogen oxide synthase
SUBSTANCE: hypoestrogen-induced endothelial dysfunction correction in white female Wistar rats, hypoestrogen-induced endothelial dysfunction is simulated by bilateral ovariectomy. The dysfunction correction is ensured by daily intragastric introduction of lozartan 6 mg/kg and daily introduction of mixed solutions of homoeopathic dilutions of polyclonal rabbit C12, C30, C200 antibodies to human endothelial nitrogen oxide synthase once a day added to drinking bowls.
EFFECT: method provides effective correction with reducing an endothelial dysfunction coefficient in females to the level observed in intact animals ensured by the effect on various developmental mechanisms of this dysfunction in hypoestrogenic conditions.
1 ex, 2 tbl
the invention relates to medicine, in particular to the experimental cardiovascolari.
Closest to the claimed solution is a way of correcting hypoestrogen-induced endothelial dysfunction furostanol glycosides from cell culture plants of dioscorea deltoidea described 27.07.2008, RF patent No. 2329807.
The main disadvantage of this method is that the correction geoastro-meningocerebral endothelial disfuncio associated with estrogen-like activity furostanol glycosides. Therefore, the results of the correction of endothelial dysfunction in case of damage in the system L-arginine-NO, which is mainly caused by deficiency of endothelial NO-synthase, using furostanol glycosides from cell culture plants of dioscorea deltoidea with estrogen-like activity is unsatisfactory.
While the main mechanism of action of the mixture of solutions gomeopaticheskih dilutions of polyclonal rabbit antibodies to endothelial synthase nitric oxide - C12, C30, C200 is an increase of eNOS, thereby affecting the main link of pathogenesis of endothelial dysfunction, leading to increased levels of nitric oxide in the vascular trunk line and correction of endothelial dysfunction; the main mechanism of action of losartan with endothelial dysfunction due is an over stimulation AT 2 subtype angiotensin II receptor and implemented due bradykininase ways of endotheliopathy, which also leads to the correction of endothelial dysfunction.
Object of the invention is a method for correcting hypoestrogen-induced endothelial dysfunction, including the use of enalapril related to antagonists of the angiotensin II receptor (AT 1-subtype) and the mixture solutions gomeopaticheskih dilutions of polyclonal rabbit antibodies to endothelial synthase nitric oxide - C12, C30, C200.
This object is achieved in that the background modeling of endothelial dysfunction in the experiment with bilateral oophorectomy in laboratory animals, is its correction within 6 weeks intragastric introduction of losartan at a dose of 6 mg/kg once per day and the daily introduction of the mixture of solutions gomeopaticheskih dilutions of polyclonal rabbit antibodies to endothelial synthase nitric oxide person - C12, C30, C200 adding to drinkers in quantities taken in homeopathy, with free access to drinking, replacement of water in the drinkers were performed 1 time per day with a quantitative accounting of fluid you drink (20±3 ml on average one animal).
The method is as follows
The experiments were carried out on white rats female Wistar weighing 200-300 g For modeling hypoestrogen-induced endothelial dysfunction in rats was narcoticyou atenalol sodium (50 mg/kg) and the province of the Dili with bilateral oophorectomy. On day 42 from the beginning of the experiment under anesthesia (eleminal-sodium 50 mg/kg) catheter in the left carotid artery for recording blood pressure (BP), a bolus of pharmacological agents in the right femoral vein. Hemodynamic parameters: systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) was measured continuously by a sensor TSD104A and hardware-software complex 100 MP, production Biopac System, Inc., USA. Functional tests: endothelium-dependent vasodilatation (ESV) - intravenous administration of acetylcholine (ach) at a dose of 40 mcg/kg, endothelium-independent vasodilatation (ANSW) - intravenous sodium nitroprusside (NP) at a dose of 30 µg/kg
The degree of development of endothelial dysfunction assessed by the coefficient of endothelial dysfunction (QED), which is the ratio of the area of the triangle above the trend of the reduction reaction of blood pressure in response to the introduction of the NP to the area of the triangle above the trend of the reduction reaction of blood pressure in response to the introduction of AH.
When the statistical processing of the data was calculated the mean value, the standard deviation value. The differences were considered significant at p<0,05.
An example of a specific implementation.
Bolus intravenous AH 3-5 with led to recompeting blood pressure, reaching a peak in the intact animals for systolic blood pressure (SBP) of 83.9±4.8 mm Hg for diastolic blood pressure (DBP) - 41,9±2.2 mm Hg and mean arterial pressure (Cf. AD) 55,8±2.2 mm Hg, while during the first 2-3 with developed sudden bradycardia up to 130-150 beats per minute (table 1).
Restoring the HELL happened in average 43,6±2.2 s after normalization of heart rate. This integral was taken as the vascular component of the reaction on the AH and was used for further calculations (table 2). ANSW was also characterized by a decrease in the GARDEN to 91,0±4,6, dad to 48.5±2.9 and Cf. HELL to 62.7±3.2 mm Hg (table 1) followed by complete recovery within average 40,2±2,4 (table 2).
Hypoestrogenemia the state, within 6 weeks after oophorectomy, called arterial hypertension (GARDEN - 160,0±6,2, dad was 124.9±5,5, Srad - 136,6±5.6 mm Hg) and lead to a smaller decline in HELL after the introduction of AH (GARDEN up to 91.8±8,0, dad to 57.3±7,1, Srad to 68.8±7,3 mm Hg) and NP (the GARDEN to 87,4±7,5, dad to 57.8±6.6 and Srad to 67,7±6.1 mm Hg) compared with intact animals (table 1).
6 weeks after the females of Wistar rats with bilateral oophorectomy was a significant decrease of the integral (response and recovery actions after the introduction of the AH) to 1022,5±131 used compared with the intact group of animals that have this indicator SOS is avsl 1673,6±132,4 used (table 1). On the contrary, ENSR, reflecting the response to the introduction of the NP increased in animals with experimental endothelial dysfunction and its integral, respectively 2157,3±167 used and 1338,1±121, 1million used in the control group.
Processing of experimental data when carrying out functional tests on endothelium-dependent (acetylcholine 40 µg/kg) and endothelium-independent (nitroprusside 30 mg/kg/in) relaxation of blood vessels in experimental animals, has allowed to establish that QED in rats intact group was 0.8, and rats after modeling hypoestrogen-induced deficiency of nitric oxide 2.5 times more - 2,1.
|Dynamics of blood pressure and heart rate when modeling hypoestrogen-induced deficiency of nitric oxide and its correction by losartan in combination with the mixture of solutions gomeopaticheskih dilutions of polyclonal rabbit antibodies to endothelial synthase nitric oxide - C12, C30, C200.|
|Groups of animals||Functional tests||GARDEN, mm Hg||DBP, mm Hg||Heart rate, beats per min|
|Intact is e||Source||128,1±6,0||95,7±4||401,0±8,0|
|Hypoestrogenic state||Source||160,0±6,2*||was 124.9±5,5*||385,0±13,0|
|Hypoestrogenic state + losartan||Source||140,1±7,0**||107,5±5,2**||405,0±14,6|
|NP||for 96.1±5,8||57,7 is a 6.2||401,3±6,8|
|Hypoestrogenic state of + losartan + blend solutions of homeopathic dilutions of polyclonal rabbit antibodies to endothelial NOS man - C12, C30, C200||Source||135,1 to±6.5**||98,7±8,7**||382,6±9,9|
|ESV with AH||94,0±5,3*||53,9±6,9*||379,4±10,1|
|ANSV with NP||106,7±5,5**||57,7±6,0*||to 369.6±12,9|
|* - p<0,05 in comparison with the group intact; ** - p<0,05 in comparison with the group with hypoestrogenism state|
Intragastric administration of losartan at a dose of 6 mg/kg once a day and add in drinkers with free access to drinking a mixture of solutions gomeopaticheskih dilutions of polyclonal rabbit antibodies to endothelial synthase nitric oxide - C12, C30, C200 (BD Transduction Labs, USA) led to the decline of the initial values of AD (GARDEN - 135,1±6,5, DBP - 98,7±8.7 mm Hg) (table 1).
Also in this group, where the background of bilateral oophorectomy for 6 weeks was administered losartan at a dose of 6 mg/kg and the mixture solutions homeopathy esih dilutions of polyclonal rabbit antibodies to endothelial synthase nitric oxide person - C12, C30, C200 QED was 1.1, which was significantly lower than in the group with hypoestrogenism condition. Whereas, in the group with losartan monotherapy, this figure amounted to 1.5 (table 2).
|Indicators that reflect the correction hypoestrogen-induced endothelial dysfunction in the background of bilateral oophorectomy with losartan in combination with the mixture of solutions gomeopaticheskih dilutions of polyclonal rabbit antibodies to endothelial synthase nitric oxide person - C12, C30, C200.|
|Groups of animals||Functional tests||The increase in the incidence of vascular response to Srad (mm Hg)||The time of the vascular response (s)||The area of the vascular response (used)||QED, usled|
|Hypoestrogenic state + losartan||OH||61,5±4,4||42,6±3,6**||1323,6±166,7||1,5±0,2**|
|Hypoestrogenic state of + losartan + blend solutions of homeopathic dilutions of polyclonal antibodies to endothelial NOS man - C12, C30, C200||OH||43,6±6,2||66,6±6,1||1349,8±105,1||1,1±0,1**|
|* - p<0,05 in comparison with the group intact, ** - p<0,05 in comparison with grupoj with hypoestrogenism state|
Thus, the obtained results allow to conclude the correction hypoestrogen-induced endothelial amid bilateral oophorectomy with losartan in combination with the mixture of solutions gomeopaticheskih dilutions of polyclonal rabbit antibodies to endothelial synthase nitric oxide person - C12, C30, C200, reducing QED to the level of that of intact animals.
The method for correcting hypoestrogen-induced endothelial dysfunction, characterized in that in the experiment the females of Wistar rats for 6 weeks after oophorectomy daily intragastrically administered losartan at a dose of 6 mg/kg daily 1 time per day administered in addition drinkers to drink a mixture of solutions of homeopathic dilutions of polyclonal rabbit antibodies to endothelial synthase nitric oxide person - C12, C30, C200.
SUBSTANCE: reservatrol efficacy is studied in female Wistar rats with simulated osteoporosis by bilateral ovariectomy. For osteoporosis correction, reservatrol is administered in animal intraperitoneally for eight weeks after ovariectomy daily once a day in single dose 2 mg/kg. Osteoprotective action of reservatrol is estimated by a bone tissue microcirculation level and width of trabeculas of bone.
EFFECT: improved blood circulation and microarchitectonics of bone tissue in hypoestrogenic condition.
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SUBSTANCE: efficacy is studied in female Wistar rats. Osteoporosis is simulated by bilateral ovariectomy. Osteoporosis is corrected by intraperitoneal introduction of reservatrol 2 mg/kg and intragastric introduction of enalapril 0.5 mg/kg daily once a day for eight weeks after ovariectomy. Osteoprotective action of reservatrol combined with enalapril is estimated by a bone tissue microcirculation level and width of trabeculas of bone.
EFFECT: improved blood circulation and microarchitectonics of bone tissue in hypoestrogen condition.
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SUBSTANCE: delimitation of a high-grade glioma invasion is ensured by imaging of an astroglial bank surrounding the high-grade glioma. An immunogenic recombinant human GFAP is prepared and used to immunise a Balb/C mouse; spleen B-lymphocyte of this mouse are recovered and fused with myeloma cells of Sp 2/0-Ag14 mice; hybridomas are produced. Supernatants of the prepared hybridomas are tested by immunochemical techniques for the presence of anti-GFAP antibodies used to select a hybrid cell clone producing the anti-GFAP antibodies able to distinguish GFAP in vivo. The anti-GFAP antibodies are cleaned from the supernatant of the selected clone and covalently bound with liposomal nanocontainers containing a diagnostic mark. The antibodies of the selected hybrid cell clone is modified by g-amino groups of lysine residues and incubated with the stelths-liposome solution. The prepared nanosystem is introduced in a patient's vascular bed, and the astroglial bank is imaged by the arrangement of the diagnostic mark in cerebral tissues.
EFFECT: method allows preventing relapses of high-grade gliomas after their surgical management by choosing an optimal extent of a pending surgery ensured by delimitation of a tumour invasion by means of imaging of the astroglial bank.
6 cl, 4 dwg, 1 ex
SUBSTANCE: originally, epiphysial hip dysplasia is formed in 10-day-old golden hamsters with projection of the joint exposed to local infra-red pulse laser light daily for 20 days. Then, on the following day, simple hip dislocation of an experimental extremity of a hamster is performed by gradual extension of a capsular-ligamentous apparatus of the hip joint. Ventral and dorsal zones of a joint space are subject to mechanical vibrations by a border of a thin metal plate fixed in a stably fixed vibrator. The following parameters are used: joint capsule pressure 1 kg, vibration frequency 100 Hz, amplitude 0.3 mm for 15 minutes to the moment of femoral head exit from an acetabular cavity. Then, the femoral head is displaced manually behind an external surface of the cavity. In 2 days, the hamster is laid on its back, and the experimental hip is gradually taken aside from a vertical plane to a position of an apex of the head of the hip joint in a horizontal plane. The procedure is performed daily for at least 3 times for 7 days.
EFFECT: use of the given invention allows performing sparing simulation of the simple hip dislocation similar to a mechanism of hip dislocation pathogenesis in children that testifies to possibility of the use of this model for studying macro- and microscopic changes in the ends of the bones formed during growth.
5 dwg, 4 ex
SUBSTANCE: in order to develop methods of treating obstructive purulent cholangitis narrowing of general bile duct at 2/3 of lumen is carried out by application of cup. After that, emptying of gallbladder is realised with simultaneous introduction as microbial suspension - suspension of E.Coli strain 303 in dilution 0.95*10^5 CFU/ml on sterile solution of 0.9% sodium chloride, in volume 0.5 ml. Microbial suspension is introduced into lumen of general gall duct above the place of cup application. Said narrowing of general bile duct lumen is supported during entire experiment duration during 10-12 days.
EFFECT: method makes it possible to obtain adequate model of said pathology due to combined influence of factors, which lead to development of morphological and patho- physical malfunctions, most closely reflecting essence of obstructive purulent cholangitis.
SUBSTANCE: invention can be used both for studying mechanisms of development of paroxysmal states with progredient course (epilepsy) and for screening (selection) of novel medications, possessing potential anti-epileptic activity. For this purpose, rats are given fractional injections of convulsant 1.5-pentamethylentetrazole (pentylenetetrazole) with 15 minute interval in dose 10 mg/kg in volume 0.1 ml solution per 100 g of body weight until fist generalised convulsive seizure develops. After that calculated is threshold dose of convulsant reflecting base level of CNS excitability for each animal. When sessions are repeated, dynamics of change of initial dose of pentylenetetrazole is taken into account, interval between sessions of pentylenetetrazole titration can constitute from 24 and more than 168 hours.
EFFECT: method ensures high accuracy of evaluation of change of seizure development threshold due to the fact that expression of modelled progredient state can be changed at any stage of carrying out chronic research without application of special methods of examination.
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SUBSTANCE: in order to correct endothelial dysfunction white male rats of Wistar line have endothelial dysfunctions modelled by intro-peritoneum introduction of N-nitro-L-arginine methyl ether in dose 25 mg/kg daily, for seven days. Degree of dysfunction development is estimated by ratio of indices of endothelium-independent and endothelium-dependent vasodilation. Correction of endothelial dysfunction is carried out by intra-peritoneum introduction of medicine "Etoxydol" in dose 25 mg/kg one time per day, for 7 days in the morning.
EFFECT: correction of endothelial dysfunction by novel derivative of 3-oxypyridine in specially developed for this purpose dose and mode of medication introduction.
2 tbl, 1 ex
SUBSTANCE: to study etiology and pathogenesis of periodontitis, and in order to define tactics of treating periodontitis in case, when evident symptoms of periodontitis exacerbation are absent carried out is modelling of periodontitis on dogs by introduction in gum around neck of upper and lower incisors of ethanol in concentration 65-75% or corticosteroid medication in amount 0.3-0.4 ml per injection.
EFFECT: increase of model credibility of disease, similar in pathomorphological menifestations to periodontitis in humans, reduction of model obtaining terms.
SUBSTANCE: for modelling of syncytial bonds between cells in vitro nervous cells, separated by known methods from ganglions of mollusc Lymnaea stagnalis are fused, after taking off their connective-tissue capsules and glial membranes. Nervous cells are placed in culture medium, centrifuged, left for 2 days.
EFFECT: method makes it possible to model and study mechanisms of multinuclear nervous cells formation and their physiological properties without fusing means and increasing medium temperature.
SUBSTANCE: invention relates to experimental physiology and is intended for measurement of individual level of cognitive abilities of laboratory animals. Problem chamber consists of two modules. Upper module is made in form of truncated hexagonal pyramid from organic glass with six outlet canals, covered with sloping hinged doors with magnets, reeds, photodiodes above each chamber door, which are switched on at purposeful pushes of sloping door inside by head or paws of tested rat during exit or attempt to open blocked door, with buzzer of sound conventional stimulus supply. Lower module represents electrode floor for aversive electric stimulation of animal's paws.
EFFECT: invention ensures increased accuracy of estimation of individual level of cognitive abilities in process of motivated by problem situation search for exit from the chamber.
SUBSTANCE: invention refers to Trecresan application for improving heart haemodynamics and reduction of metabolic disorders in treating the patients suffering arterial hypertension and obesity, and also its combinations with ATE inhibitors.
EFFECT: higher clinical effectiveness.
3 cl, 3 tbl, 3 ex
SUBSTANCE: invention relates to compounds of formula (I) given below or pharmaceutically acceptable salts thereof:
[where: each of X, Y, Z and W independently denotes a methane group which optionally contains substitutes selected from a group of substitutes α, or a nitrogen atom (except when all elements X, Y, Z and W denote a methane group which optionally contain substitutes selected from the group of substitutes α); A denotes -(C(R3)(R4))m1-; B denotes -O-; D denotes -C(O)-; m1 equals 0; Q denotes a methane group or a nitrogen atom; R denotes a group of formula (II)
, where R6 denotes a lower alkyl group; R7 and R8, together with the nitrogen atom with which they are bonded, form a 5-6-member nitrogen-containing aliphatic heterocyclic group; and where the group of substitutes α includes the following substitutes. Group of substitutes α: halogen atom, hydroxyl group, lower alkyl group, alkoxyl group (said group can be substituted with a cycloalkyl group), amino group, mono- or disubstituted lower alkylamino group, aryl group (said group can be substituted with a halogen atom, a -SO2CH3 group), aryloxy group (said group can be substituted with a halogen atom), heteroaryl group, where 'heteroaryl group' denotes a 5- or 6-member monocyclic saturated or unsaturated group containing 1-2 heteroatoms selected from an oxygen atom or a nitrogen atom (said group can be substituted with an alkoxyl group, alkyl group). The invention also relates to a histamine 3 receptor antagonist, histamine 3 receptor inverse agonist, a prophylactic or medicinal agent, as well as a pharmaceutical composition.
EFFECT: obtaining novel biologically active compounds having histamine H3 receptor antagonist or inverse agonist action.
15 cl, 57 ex, 1 tbl
SUBSTANCE: invention refers to indole-3-yl-carbonyl-spiro-piperidine derivatives which have an effect of Vla-receptor antagonists and are presented by Formula I: where a tail spiropiperidine group A and residual R1, R2 and R3 are such as specified in the patent claim.
EFFECT: higher efficiency of applying the compounds in drugs effective in dysmenorrhea, hypertension, chronic heart failure, inadequate vasopressin secretion, hepatic cirrhosis, nephrotic syndrome, obsessive-compulsive disorder, anxious and depressive disorders.
22 cl, 42 ex
SUBSTANCE: invention relates to medicine, namely to cardiology, hematology, and can be applied for reduction of spontaneous erythrocyte aggregation in case of arterial hypertension with metabolic syndrome. For this purpose administered are dosed static and dynamic physical activity, daily swimming for not less than 40 min. per day in the middle of the day, as well as lisinopril in dose 10 mg 1 time per day in the morning and methformin 500 mg 2 times per day. Physical activity includes morning hygienic gymnastics, therapeutic-preventive gymnastics and divided physical exercises during the day. Treatment course is 2 months.
EFFECT: combination of treatment methods makes it possible to reduce spontaneous erythrocyte aggregation, which assists prevention of thrombotic complications in said category of patients.
SUBSTANCE: invention refers to medicine, namely to haematology and cardiology, and concerns reducing spontaneous erythrocyte aggregation (SEA) in arterial hypertension with impaired glucose tolerance.. That is ensured by the integrated treatment that involves the administration of lisinopril 10 mg once a day in the morning and metformin 500 mg twice a day for 2 months, as well as graduated static and dynamic physical activity, including daily swimming for at least 30 minutes a day.
EFFECT: complex of drug-induced and drug-free modalities ensure reducing the SEA for 2 months that in turn promotes normalised blood rheology and reduced risk of thrombotic complications in the case patients.
SUBSTANCE: invention relates to medicine, namely to gerontology and cardiology and can be used for reduction of pathologically increased biological age (BA) in patients with arterial hypertension (AH) with abdominal obesity (FO) and dyslipidemia. Essence of claimed method lies in the following: to patients administered is complex, that includes hypocaloric diet, calculated in kcal by formula: for women: 18-30 years old - (0.0621 × body weight, kg + 2.0357) × 240; 31-60 years old - (0.0342 × body weight, kg + 3.5377) × 240; over 60 years old - (0.0377 × body weight, kg + 2.7545) × 240; for men: 18-30 years old- (0.0630 × body weight, kg+ 2.8957) × 240; 31-60 years old - (0.0484 × body weight, kg + 3.6534) × 240; over 60 years old - (0.049 × body weight, kg + 2.4587) × 240. Also administered are rationally dosed static and dynamic physical loadings, including morning hygienic gymnastics, preventive medical gymnastics, fractional physical exercises during the day, daily swimming in swimming pool for not less than 60 minutes per day. Also introduced are medications simvastatin 10 mg 1 time before going to bed after meal and lisinopril 10 mg 1 time per day in the morning for not less than 7 weeks.
EFFECT: invention combines application of all components of complex allows to normalise BA within 7 weeks of treatment.
SUBSTANCE: invention refers to medicine, namely to gerontology and cardiology, and concerns biological age reduction in arterial hypertension combined with abdominal obesity. That is ensured by the integrated treatment including a low-calorie diet, reasonable graduated static and dynamic physical activity, daily swimming in a pool for at least 30 minutes, and the introduction of lisinopril in dosage 10 mg once a day in the morning and metformin in dosage 500 mg twice a day for the therapeutic course of 7 weeks.
EFFECT: complex of drug-induced and drug-free therapy combined with empirically prescribed treatment length provides biological age reduction in the case patients estimated by the relation of electronegative cells to total count in a buccal epithelium scrape due to normalised DNA repair and chromosome fragility level.
SUBSTANCE: invention belongs to medicine, notably to haematology and cardiology and refers to reduction of spontaneous erythrocytes aggregation in patients with arterial hypertension. This is ensured by the integrated treatment including graduated static and dynamic physical loads, including daily swimming for at least 20 minutes in the middle of the day, daily, and administration of lisinopril 10 mg once a day in the morning and amlodipine 10 mg once a day in the morning.
EFFECT: combined drug-free and drug therapies during empirically fitted period ensure effective reduction of spontaneous aggregation of erythrocytes, which, in turn, allows to improve blood's rheological properties and reduce risk of thrombotic complications in patients with arterial hypertension.
SUBSTANCE: invention refers to medicine, namely to obstetrics, and concerns the correction of antihypertensive preparations (AHP) dosage in pregnant women with arterial hypertension. It involves Doppler ultrasound of the "mother-placenta-foetus" system. The uteroplacental misperfusion severity is evaluated. The IA or IB severity level require the AHP dosage to be reduced by 25% as compared to the initial one, while in the II severity level, the dosage is to be reduced by 50%, and in the III severity level - by 75%.
EFFECT: method provides optimised antihypertensive therapy in the pregnant women with taking into account the misperfusion severity level in the "mother-placenta-foetus" system, and as consequence, decreased number of foetal growth inhibition cases and improvement of pregnancy terminations.
SUBSTANCE: invention refers to medicine, namely to cardiology, and concerns treatment of patients with hypertrophic cardiomyopathy. That is ensured by genotype determination, and genotype AA ATR1 requires introduction of irbesartan in dosage 75-300 mg once a day.
EFFECT: higher clinical effectiveness in the case patients.
7FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to a combination of a co-drug (an auxiliary) and a compound o formula (IV) in which radicals and symbols have the values defined in cl. 1 of the patent claim, or salts, or tautomers, or N-oxides, or solvates of this compound; where the specified auxiliary is specified from a monoclonal antibody, an alkylating agent, a malignant growth agent, other cycline-dependent kinase (CDK) inhibitor and a hormone, a hormone agonist, a hormone antagonist or a hormone-modulating agent specified in cl. 1 of the patent claim. The offered combination is used for tumour cell growth inhibition.
EFFECT: invention also refers to a pharmaceutical composition based on the offered combination, application of the combination and its separate ingredients and methods of treating, preventing and relieving the cancer symptoms in a patient.
77 cl, 2 dwg, 8 tbl, 257 ex