Method for rehabilitation of elderly patients with ischemic heart diseases accompanied by chronic heart insufficiency following myocardial infarction

FIELD: medicine.

SUBSTANCE: invention concerns rehabilitation of elderly patients with ischemic heart disease (IHD) accompanied by chronic heart insufficiency (CHI) following myocardial in myocardial infarction (MI). That is ensured by administering Omacor, a preparation of omega-3-polyunsaturated fatty acids in the remote period, 6 or more months after the suffered MI with underlying a standard drug therapy 60 minutes before the graduated walking.

EFFECT: this complex of the drug preparations combined with the graduated physical exercises provides higher tolerance to physical exercises, improving the cardiovascular function and normalising the lipid exchange that in turn leads to reducing a number of unfavourable cardiovascular episodes and delaying CHI.

2 ex, 5 tbl

 

The invention relates to medicine and can be used in cardiology and rehabilitation for the physical rehabilitation of older patients after myocardial infarction (mi).

Modern tactics of treatment of patients with coronary heart disease (CHD), are burdened with chronic heart failure (CHF), includes physical rehabilitation. According to several clinical studies, and meta-analysis of Extranets dosed physical load have a positive impact on the prognosis of patients with CHF [1]. According to the results of the meta-analysis of Extranets among patients who trained during the year, the mortality rate decreased by 35%, on the basis of what physical exercise were assigned to class I recommendation (level of evidence B) for the diagnosis and treatment of chronic heart failure [2].

However, many questions concerning the training of such patients (dates of commencement of training, duration, background medical therapy) remain unresolved; in other words, it is still not the optimal program of cardiac rehabilitation of older patients with heart failure after myocardial infarction [3, 4]. In particular, according to Nikolaeva L. F., Aronov D. M. long-term physical exercise for patients undergoing THEM, it is permissible to start in 3-4 months after it [5], but in relation to the timing of physical rehabilitation at �oilah CHD patients with CHF, mi, consensus does not exist. The progression of CHF is determined by the rate of post-infarction remodeling of the myocardium that can last weeks or months, but, according to Perutsky D. N. et al. (2011) to 6th month after myocardial infarction is becoming apparent lack of progression of heart failure due to ended processes of remodeling, or in the future after myocardial infarction CHF will have to be made quickly - or umerennoplotnye character [6].

In the Russian Federation currently about 25% of the population are aged over 65, which, in accordance with the documents of the UN and the International labour organization, are considered elderly [7]. Patients of older age groups is prone to complicated course of myocardial infarction and are often burdened with comorbidities. As a method of early rehabilitation in patients with IHD, mi, hospital schemes offered group and individual physical therapy, which has repeatedly shown its effectiveness and positive predictive influence, however in the older age groups group barely acceptable rehabilitation, and personal training is not possible due to organizational and economic difficulties [7].

Known method of rehabilitation of elderly patients with CHF, moving� THEM on the sanatorium stage of rehabilitation in which to reduce the risk of recurrent cardiovascular events and improve the quality of life of patients used a set of physical exercises using the exercise bike and measured distance under the control of Central hemodynamics [8].

This method is the closest to the claimed technical essence and achieved clinical result and selected as a prototype.

The disadvantage of this method is that the effectiveness of controlled training limited neskorrigirovannoe of circulatory hypoxia in chronic heart failure after myocardial infarction, in addition, also it is applicable only to short sanatorium stage of rehabilitation of elderly patients after myocardial infarction, due to the necessity of using special technical devices, such as an exercise bike, which severely limits the application of this method to patients in the home.

The object of the invention is to improve the efficiency of the method of rehabilitation of elderly patients in the late period after mi.

The problem is solved by assigning long-term (6 months or more) patients after myocardial infarction coronary heart disease associated with chronic heart failure, amid �standard drug therapy for 60 minutes before the start of controlled physical exercise via controlled walking of the antioxidant - drug omega-3-polyunsaturated fatty acids (ω-3 PUFA) - Omacor.

New in the proposed method is the appointment of older patients with CHD and CHF after 6 months or more after myocardial infarction drug ω-3 fatty acids Omacor 60 minutes before the start of controlled physical training in the form of controlled walking.

The proposed method of rehabilitation is based on the fact that it is based on the effects of ω-3 PUFA on these trigger factors for the development of chronic heart failure in patients who underwent THEM, both diastolic and systolic myocardial dysfunction and hypertensive left ventricular hypertrophy that, ultimately, providing a regression of ischemic myocardial dysfunction, will reduce the total number of adverse cardiovascular events [9]. In particular, in studies R. Green (2007) and Arena R. (2008) showed that CHD patients with CHF, the decrease in the pumping function of the heart after myocardial infarction is associated with reduced peak oxygen consumption of the myocardium of the heart and the body in General, which is an independent predictor of cardiac death and adverse cardiovascular events [10, 11]. According to the study GISSI-HF, it is established that the appointment of CHD patients with CHF drug Omacor provided a significant reduction in total mortality by 9% and frequency hospitalizat�th due to cardiovascular causes by 8% within 90 days of treatment, but in the future do not affect the prognosis of patients after AMI [8, 12, 13]. Thus, in the meta-analysis Poole CD. et al. (2013) submitted that the appointment of ω-3 PUFA in the first 14 days. after AMI leads to a statistically significant reduction in the risk of death by 32%, in the first 90 days. - 22%, but the beginning of therapy of ω-3 PUFA more than 90 days. after suffering the AMI has virtually no effect on the prognosis [14]. In addition, M. F. Piepoli et al.(2004) found that the use of physical training in patients with coronary artery disease associated with severe functional classes of heart failure, can reduce not only the number of adverse cardiovascular events, but also to improve the quality of life of patients [1]. However, data on the use Omakora in elderly patients with CHD and CHF, mi, insufficient, and in long-term rehabilitation programs that include physical exercise, such patients are usually not included.

The technical result of the invention is improving the efficiency of the method of rehabilitation of elderly patients with chronic ischemic heart disease heart failure, mi, which will improve the quality of life and reduce the risk of adverse cardiovascular events.

The technical result is achieved by assigning long-term (6 months or more) after pertenecen�their older patients with chronic ischemic heart disease heart failure on the background of the controlled physical exercise antioxidant Omakora in addition to the primary therapy. This makes it possible to provide more effective and safe approaches to rehabilitation in elderly patients with CHD and CHF, mi, through the implementation of: 1) protection of the myocardium from the toxic action of peroxidation, reduce the loss of cardiomyocytes (way of necrosis and apoptosis); 2) anti-ischemic actions - improvement of both systolic and diastolic myocardial function of the left ventricle; 3) reduce damage of the endothelium under the influence of stress hemodynamic effects.

Distinctive features showed in the inventive combination of new properties that are not explicitly derived from the prior art in this field and not obvious to the specialist. Identical set of features in the reviewed literature is not detected. The present invention can be used in health care.

Based on the above, should be considered as the invention with the relevant conditions of patentability of "Novelty", "Inventive step", "Industrial applicability".

The method is as follows.

Before treatment to determine the tolerance to physical activity by the Bicycle stress test (VEM). For this sample performed at a speed of pedaling at 60 rpm for 1 minute, with a stepped, continuously growing �batch, starting at 25 W, followed every minute by increasing the load at 10 watts before reaching the termination criteria of the sample, such as:

- the emergence or strengthening of anginal pain moderate and severe intensity;

- pale skin, cyanosis (signs of hypoperfusion);

- sustained ventricular tachycardia;

- lifting ST for 1 cm or more (except VI and aVR);

- depression of ST segment>=4 mm;

- increasing chest pain;

- estimated achievement of maximal or submaximal heart rate.

6 months after myocardial infarction, in patients receiving standard therapy, including aspirin at a dose of 75 mg/day, ACEI (Enap in dose from 5 to 40 mg/day, chosen individually), diuretic (hydrochlorothiazide - in a dose of from 12.5 to 75 mg/day, chosen individually), α1β1β2-adrenoblocker (carvedilol - in a dose of from 6.25 to 50 mg/day, chosen individually) for 60 minutes before the start of controlled physical exercise (controlled walking) the patient is taking Omacor 1 time per day throughout life.

The patient then performs dosed walking, from 0.5 km at the pace of the walk 70 steps per minute to 2 km at the pace of 100-110 steps per minute at a distance of from 2 to 10 km, while the patient himself controls the distance and walking speed on the basis of its satisfactory condition of absence of anginal attacks, and the fact that the frequency with�technich cuts should be no more than 60% of the maximum set according to the results of the event. Every 3 months they control the physical condition of the patient using VEM samples, and, if necessary, adjust the level of physical activity (based on the results obtained VEM).

We examined 68 patients with coronary heart disease with chronic heart failure after 6 months or more after myocardial infarction in anamnesis (39 men and 28 women) aged 60 to 77 years (average age was 65.3±6.8 years). By simple random sampling were divided into two groups: group physical training in patients receiving Omakora (according to the suggested method) - 35 patients (group "Omacor+training") in patients receiving aspirin at a dose of 75 mg/day, α1β1β2 the use of carvedilol (at a dose ranging from 6,125 mg/day in two divided doses, with subsequent increase up to the maximum tolerated (average of 19.6±5.4 mg/day), and ACE Enap (at a dose ranging from 5 mg/day to a maximum dosage of 40 mg/day) and the diuretic hydrochlorothiazide (at a dose ranging from 12.5 mg/day to a maximum dosage of 75 mg/day) and a comparison group without the use of the proposed method is of 33 patients.

For each patient filled a specially designed clinical map. All patients gave their written informed consent to participate in the study. The condition of patients was evaluated at baseline and after 6 months the analysis of the frequency of the composite end point that included: mortality, ince�of LT, re-hospitalization for CHF exacerbations, repeated THEM. It also measured the systolic function of the left ventricle (according to the ECHO) and physical tolerance according to test 6-minute walk. Additionally evaluated the lipid spectrum of blood.

Evaluation criteria good anti-ischemic and hemodynamic effects of the proposed method considered: regression of CHF symptoms, decrease the frequency and severity of angina, reduction of the daily requirement of nitrates, increase exercise tolerance test results of 6-minute walk.

The study included patients whose condition remained stable for at least 2-3 weeks on a regular basic therapy that included desegregate, ACE inhibitor, β-blocker, statin, diuretic and, if necessary, antagonist of aldosterone.

At the time of inclusion in the study patients in both groups did not differ on major indicators, such as age, gender, comorbidity, severity of heart failure received drug therapy. After randomization, the patients of study group in addition to standard therapy received complex physical rehabilitation of the proposed scheme and the drug Omacor.

Statistical analysis of the obtained digital data was performed using the program STATISTIA 6.0 (StatSoft, USA).

The results of observation of patients studied groups after 6 months are presented in table 1. In the group of patients receiving the drug Omacor, amid controlled workouts were diagnosed significantly fewer deaths, strokes and recurrent myocardial infarction. While in the study group hospitalizations statistically significantly less likely to be registered re-hospitalization for decompensation of heart failure and adverse cardiovascular events (11.4 percent vs. 30.3 per cent, p=0,029; 25,7% vs 57.6 per cent, p=0.015, respectively).

Table 1
The incidence of the combined endpoint in study groups after 6 months of observation
IndicatorsThe comparison group (n=33)Group Omacor+exercise (n=35)P
Cardiovascular death3 (9,1%)-0.217
Myocardial infarction5 (15,2%)2 (5,7%)0.378
Stroke1 (3,0%)- 0.976
Hospitalization with CHF decompensation10(30,3%)4(11,4%)0.029
The total number of adverse cardiovascular events19(57,6%)6(17,1%)0.001

According to the ECHO-KG revealed that in the group of physical training in patients receiving Omakora significant (20.4%, p=0.001) increase in LVEF and explicit (11.7%, p=0.001) reduction in end-systolic LV volume. The same group also showed a significant increase in exercise capacity and the reduction in the number of angina attacks per week - 33.8% (p=0.001) (table 2).

In addition, significant antiatherogenic effect of the proposed method, namely: the decrease in total blood cholesterol by 23% (p=0.001), a decrease in the content of atherogenic low density lipoprotein (LDL) and triglycerides by 23 and 28% (p=0.001), respectively, increased content of antiatherogenic high density lipoprotein (HDL) - 11.6% (p=0.001) (table 3).

Thus, after 6 months or more after myocardial infarction, admission for 60 minutes before the start of controlled physical exercise antioxidant - preparation of ω-3 PUFA - Omacor on the background with�andartes drug therapy of elderly patients with chronic ischemic heart disease heart failure ensured a significantly lower rate of re-hospitalization for progression of CHF and the total number of adverse cardiovascular events. In addition, it was registered a significant improvement of the clinical course of coronary artery disease and heart failure: marked fewer angina attacks per week, to improve tolerance to physical activity, and improvement in systolic function of the heart. Any negative coronarienne or hemodynamic effects has not been established.

The proposed method of rehabilitation of elderly patients with coronary heart disease with chronic heart failure, mi, is illustrated by the following clinical examples.

Example 1 (2013). Patient K., 67 years old, was admitted in a planned manner to the medical ward with a diagnosis of coronary artery disease: angina of II FC. Postinfarction (2009) cardio. NC IIA. CHF FC III (NYHA).

Upon receipt complained of shortness of breath is the type of "lack of air" with little exertion, weakness and rapid heartbeat.

Objectively: General condition of the patient of moderate severity due to the decompensation of CHF. The active position. The right physique. The asthenic Constitution. Nutrition normal. Skin clean, Norma�humidity encourages creativity, pale, diffuse cyanosis. Lymph nodes are not enlarged. Trophic changes both shins (induration). Varicose veins of the extremities. Musculoskeletal system, no obvious changes in the Number of respiratory movements in 20 minute. Regular rhythm. Breathing through the nose freely. Neck veins were not dilated. Percussion sound over the lungs clear, pulmonary. Vesicular breathing with a hard tone. Listened to a small number of wheezes. The region of the heart is not changed. Apical impulse in V intercostal space at mid-clavicular line. The cardiac impulse is not defined. Muffled heart sounds. Heart rhythm correct. Heart rate of 85 beats per 1 minute. In clinical analysis of blood symptoms of anemia mild (HB 117 g/l, er of 3.98×109/l). In the clinical analysis of urine without pathological changes. During ECHO study, a small increase in LV cavity. Hypo - and akines the top. Left ventricular ejection fraction of 46%, Aorta sealed - 36 mm (PL.4).

Table 4
The figures ECHO and lipid profile of the patient K.
IndicatorsThe in-hospital phase3 months
The ECHO-KG
The CRA LV (cm)6,2CEB LV (cm)The 4.674,2
PL (cm)4,14,1
IVS (cm)1,21,1
Ssli (cm)1,21,1
EF (%)4651
Lipid profile
The total cholesterol (mmol/l)6,75,4
TG (mmol/l)1,41,0
LDL (mmol/l)4,633,8
HDL (mmol/l)1,020,8

In the hospital, was appointed therapy: bisoprolol 5 mg, enalapril 2.5 mg × 2 times a day, morning and evening; aspirin cardio 100 mg in the afternoon, plaice 75 mg in the morning, verospiron 25 mg × 4 times a day, atorvastatin 40 mg at night. To customised doses of drugs with the first day of hospitalization, was added to the drug omega-3-LM�tions acids (Omacor) in a dose of 1000 mg/day. At discharge the patient from hospital according to the ECHO KG registered positive dynamics in the form of growth of PV 51% (10.9%) in 10 days after discharge from the hospital in a planned manner was conducted VEM test: ET - 75 watts, submaximal heart rate is 98 beats per minute. Thereafter the patient was recommended dosed walking from 0.5 km at the pace of the walk 70 steps per minute to 2 km at the pace of 100-110 steps per minute at a distance of from 2 to 10 km, in this case, he must control the distance and walking speed on the basis of their satisfactory condition of absence of anginal attacks, and the fact that the heart rate should be no more than 60% of the maximum installed. After 3 months, when you hold VEM revealed positive dynamics in the form of increased ET to 125 watts and growth submaximally with heart rate 98 beats per minute to 116 beats per minute.

EXAMPLE 2 (2013). Patient D., aged 71, retired. Was admitted to the medical ward with a diagnosis of coronary artery disease: angina of II FC. Postinfarction (2012) cardio. Paroxysmal AF. Rare supraventricular extrasystoles. Paroxysmal supraventricular tachycardia. NC II, CHF FC III (NYHA). Hypertension III grade Risk 4.

Upon receipt of the complaint on the AD to 170/90 mm Hg.CT., soprovojdavshie�Xia dizziness, headache, unsteadiness when walking, reduced concentration; shortness of breath type of "lack" of air with a slight FN - trunk bending, self-service; cough without sputum, "whistles" in the chest, swelling of the legs. The present deterioration in health in the form of the above complaints during the week.

Objectively: the state of moderate severity, due to the decompensation of CHF. The active position. The right physique. The asthenic Constitution. The power is increased. Consciousness is clear. Skin clean, normal humidity. Lymph nodes - b/O. the Thyroid gland is not palpable. Musculoskeletal system - not visually changed. Percussion over all lung fields clear pulmonary sound. Vesicular breathing in the lungs, the weakening of the posterior surface of the thorax with two sides, no wheezing. Respiratory rate 19 / min. Digestive organs: tongue moist, clean. Abdominal palpation soft, painless. The liver is palpated. (+) 4-5 cm from under the costal arch, the edge is smooth, pointed, slightly painful, tightly-elastic. Gallbladder symptoms negative. Chair daily, decorated. The region of the heart is not changed. Apical impulse in V intercostal space 1 cm medially from the mid-clavicular line. The cardiac impulse is not defined. Heart sounds rhythmic, muted. Noise no. BP 150/70 mm Hg.with�; heart rate 80 per minute. Genitourinary system: the lumbar region is not visually changed. The kidneys are not palpable. Cm of a beating negative on both sides. Diuresis is not speeded up, painless. Pastoznost foot and lower third of the tibia. Varicose veins of the legs. When ECHO examination revealed slight enlargement of PL. Of myocardial hypertrophy was not detected. Contractility, reduced LV ejection fraction (- 50%). Hypo-akinesia posterior and postero-basal LV segments. Atherosclerosis of the aorta, the valves ALC. Sash MK sealed. MK and TC failure. Diastolic dysfunction of LV - 1 type (PL.5).

Table 5
The figures ECHO and lipid profile of the patient D.
IndicatorsThe in-hospital phase3 months
ECHO
The CRA LV (cm)5,55,7
CEB LV (cm)4,064,1
PL (cm)4D4,2
IVS (cm)1,06 1,1
Ssli (cm)1,061,1
EF (%)5052
Lipid profile
The total cholesterol (mmol/l)5,95,6
TG (mmol/l)2,52,2
LDL (mmol/l)4,74,02
HDL (mmol/l)0,81,01

In the hospital, was appointed therapy: amlodipine 5 mg × 1 time a day, aspirin cardio 100 mg × 1 time a day, diver 10 mg × 1 time per day, silt 75 mg × 1P/day, amlodipine 5 mg × 2 times a day, Concor 5 mg × 1 time per day, atorvastatin 40 mg overnight.

In the hospital of physical exercise was not conducted in connection with the decompensation of hypertension. From the hospital, was discharged on the 11th day, with improvement in stabilization of blood pressure within target levels, improve the General condition, the relief of headache, dizziness, lack of signs of rise of heart failure: reduction of dyspnea during physical on�ruske, edema swelling of the lower extremities. 14 days after discharge from the hospital routine was performed Treadmill test: ET - 50 W, submaximal heart rate is 112 beats per minute.

After 3 months, when you hold the treadmill test was revealed weak positive dynamics in the form of a marginal increase in ET to 60 watts and the lack of a statistically significant increase submaximally with heart rate 112 beats per minute to 116 beats per minute. When controlling the dynamics of lipid: total cholesterol, LDL, TG authentically did not change significantly. ECHO KG significant improvement of intracardiac hemodynamics were not identified.

Thus, the purpose of the preparation of ω-3 polyunsaturated fatty acids Omacor 60 minutes before the start of controlled physical training in the form of controlled walking on a background of standard medical therapy in elderly patients with CHD and CHF, in the long-term (6 months or more) after myocardial infarction, increases tolerance to physical loads, provides positive changes in indicators of ECHO and lipid spectrum of blood and reducing the total number of adverse cardiovascular events, contributes to reducing the progression of heart failure.

The proposed method was applied in 33 patients and improves the efficiency of rehabilitation p�residential CHD patients with chronic heart failure, mi, through the implementation of anti-anginal, anti-ischemic and hemodynamic effects.

References

1) M. F. Piepoli, Davos C, Francis D. P. et al. Exercise training meta-analysis of trials in patients with chronic heart failure (ExTraMATCH) // BMJ. - 2004. - Vol.328. - P. 189.

2) Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Eur Heart J.- 2008. - №29. - 2388-2442.

3) Catherine De Maeyer, Paul Beckers, et al. Exercise Training in Chronic Heart Failure // Ther Adv Chronic Dis. - 2013. - 4(3). - 105-117.

4) Cardiac rehabilitation: a practical guide. Ed. by J. Niebauer. - translated from English., ed. by Y. M. Pozdnyakov. - M.: The Logosphere, 2012. - 328 with (p. 101).

5) Nikolaeva, L. F., Aronov D. M. exercise therapy for myocardial infarction and chronic coronary heart disease // Medical physical culture / ed. by V. A. Epifanova. - 2nd ed. - M., 2002.

6) Perutsky D. N., Makeeva T. I., Konstantinov S. L. Basic concepts of postinfarction remodeling of the left ventricle myocardium. SCIENTIFIC STATEMENTS. Series Medicine. Pharmacy. - 2011. - 10(105). - Vol.14. - 51-59.

7) cash-strapped A.V. Use of passive muscle training in complex rehabilitation of myocardial infarction in elderly patients. Abstract of the Cand. Diss. - 2011. - 23 p.

8) the patent for the invention № RU 2329780 from 20.07.2006. Author(s): Bagaudinova O. V., Zaitsev N. M. Avdonchenko T. S., Tarasov, NO., Gzogyan M. N. The patentee(s): JSC Sanatorium "Prokopyevsk".

9) National guidelines PRAS, CSC and REMOT for the diagnosis and treatment of CHF (fourth revision). ISSN 1728-4651. Journal of Cardiac failure. - Tom 14. - №7(81). - 472 S.

10) Arena, R., Myers, J., Abella J., et al. The partial pressure of resting end-tidal carbon dioxide predict major cardiac events in patients with systolic heart failure. Am J Cardiol. - 2008. - Vol.156. - 982-988.

11) Green P., Lund, L. H., Mancini D. Comparison of Peak Exercise Oxygen Consumption and the Heart Failure Survival Score for Predicting Prognosis in Women Versus Men. Am J Cardiol. -2007. - Vol.99. - 399 - 403.

12) Macchia A, Levantesi G, Franzosi MG, et al., for the GISSI-Prevenzione Investigators. Left ventricular systolic dysfunction, total mortality, and sudden death in patients with myocardial infarction treated with n-3 polyunsaturated fatty acids. EurJ Heart Fail. - 2005. - Vol.7. - 904-09.

13) Finzi, A. A. Effects of n-3 polyunsaturated fatty acids on malignant ventricular arrithmias in patients with chronic heart failure and implantable cardioverter-defibrillation: a Substady GISSI-HF / A. Finzi A, R. Latini, S. Barlera at al. Am. Heart J. - 2011. - Vol.161. - P. 338-343.

14) Poole CD., Halcox J. P., Jenkins-Jones, S., E. S. Carr, Schifflers M. G., K. K. Ray, C. J. Currie Omega-3 Fatty acids and mortality outcome in patients with and without type 2 diabetes after myocardial infarction: a retrospective, matched-cohort study. Clin Ther. - 2013. - Vol.35(1). - 40-51. doi: 10.1016/j.clinthera.2012.11.008. Accessed on 23.06.14.

Method of rehabilitation of elderly patients with ischemic heart disease with chronic heart failure, myocardial infarction, consisting in the carrying out of physical training through controlled walking on a background of standard medical therapy with antiplatelet agents, β1-adrenal�katorumi, diuretics and ACE inhibitors, characterized in that when carrying out controlled walking after 6 months or more after myocardial infarction in 60 minutes before physical training, patients are prescribed the drug omega-3-polyunsaturated fatty acids (Omacor).



 

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FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to the pharmaceutical industry and provides a multilayered tablet, containing an effervescent layer, containing hydrochlorothiazide or amlodipine or its salt as an active ingredient, carbonate salt and organic acid, and a telmisartan-containing layer.

EFFECT: obtaining the multilayered tablet, containing the effervescent layer.

1 dwg, 9 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: invention provides a method of producing pesticide microcapsules via a nonsolvent deposition method, characterised by that the active substances used are heterocyclic compounds of the triazine series and the envelope is polyvinyl alcohol, which is deposited from an aqueous solution by adding butanol and isopropanol at 25°C as the nonsolvent.

EFFECT: simple process of producing microcapsules of a preparation in water-soluble polymers, high mass output.

3 ex

FIELD: medicine.

SUBSTANCE: invention refers to experimental medicine and can be used to work out drug therapy of acute pancreatonecrosis with its efficacy to be followed by a histological study. That is ensured by simulating pancreatonecrosis in animals. That is followed by intravenous introduction of the compound "2-morpholino-5-phenyl-6H-1,3,4-thiadiazine hydrobromide" of 1,3,4-thiadiazines in a dose of 40 mg/kg.

EFFECT: method provides effective treatment of pancreatonecrosis, including by managing an acute phase of a systemic inflammatory response, increasing a probability of the recovery, and reducing a mortality.

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to novel compounds of formula I: where n has values 0 or 1, and Cy represents a heteroaryl group, selected from such groups as 2-furanyl, 3-furanyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl and 4-pyridinyl, where heteroaryl groups are optionally substituted by up to 3 substituents, different from hydrogen, independently selected fromC1-6alkyl, C2-6alkenyl, C2-6alkinyl, C3-8cycloalkyl, substituted phenyl, furyl, halogen, -OR', -CF3, -CN, -NO2, -SO2R', -SO2NR'R″, -R'SO2R″, where R' and R″ are independently selected from hydrogen, C1-6alkyl, where the term "substituted", applicable with respect to substituted phenyl, relates to substitution with one or several halogens, and their pharmaceutically acceptable salts, as well as to pharmaceutical compositions based on the said compounds.

EFFECT: application of the said compounds for treatment and/or prevention of wide spectrum of CNS diseases and disorders.

13 cl, 2 dwg, 1 tbl, 11 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to medicine and describes solid peroral drug form in form of pill, which includes: a) therapeutically effective quantity of aliskiren or its pharmaceutically acceptable salt, b) therapeutically effective quantity of hydrochlorothiazide (HCTA), and c) hydrophilic filler, which represents mixture of wheat starch and lactose. Method of obtaining solid pharmaceutical composition as well as its application are described.

EFFECT: invention ensures considerable solidity and short time of disintegration of peroral form.

28 cl, 7 ex, 8 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a pharmaceutical composition the form of an oral suspension consisting of valsartan or a pharmaceutically acceptable salt thereof and at least one or two or more ingredients specified in glycerol or a syrup or a mixture thereof, a preserving agent, a buffer system, a suspending/stabilising agent and anti-foaming agent. The buffer system is specified in sodium citrate, potassium citrate, sodium bicarbonate, sodium dihydrophosphate and potassium dihydrophosphate, and maintains pH of the composition within the range of 3.0 to 5.0. Further, the present invention refers to using the pharmaceutical composition for preparing a drug.

EFFECT: orally administered valsartan suspension provides high bioavailability and reduced variability of response to the administered dose when administered to different subjects or one subject.

10 cl, 4 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: pharmaceutical composition by invention possesses antagonistic activity with respect to angiotensin II. Pharmaceutical composition contains 30-80 wt % of inrbesartan or its pharmaceutically acceptable salt as active ingredient and more than 10 wt % of loosening agent in terms of complete composition weight. Pharmaceutical composition does not contain silicon-containing antiadhesive. Pharmaceutical composition of irbesartan is made in form of tablet with film coating. Also described is method of irbesartan tablet manufacturing.

EFFECT: irbesartan tablet possesses dissolution profile at which 80 wt % or more of irbesartan dissolve not later than after 30 min.

25 cl, 1 dwg, 10 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to cardiology and deals with increase of antihypertensive therapy efficiency and reduction of left ventricle hypertrophy in patients with arterial hypertension of 2-nd degree with high risk of development of cardio-vascular complications (risk 3). For this purpose antihypertensive therapy is performed taking into account prevailing temperament or prevailing part of vegetative nervous system, as well as personality anxiety. With account of said factors elaborated are versions of complex therapy, namely: a) beta-adrenoreceptor antagonist (BAA) and diuretic in average day dose in combination with anxiolytic in minimal day dose; b) BAA and diuteric in minimal day dose; c) ACE inhibitor and diuretic in average day dose in combination with antidepressant in minimal day dose; d) ACE inhibitor and diuretic in minimal day dose and antidepressant in minimal day dose.

EFFECT: method ensures efficient treatment of arterial hyopertension and prevention of acute disorders in blood circulation system due to differentiated administration of drug therapy taking into account psychoemotional background in said group of patients.

5 ex, 23 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to 2-aminopropylmorpholino-5-aryl-6H-1,3,4-thiadiazines, dihydrobromides (of general formula I) and 2-aminopropylmorpholino-4-arylthiazoles, hydrobromides, (of general formula II) which show antiaggregant activity. wherein R = H; F; CI; Br; OH.

EFFECT: given compounds may be used for preparing cardiologic drugs and enable better treatment of various cardiovascular diseases, including myocardial infarction and thrombotic apoplexy.

1 cl, 2 tbl

FIELD: medicine.

SUBSTANCE: present invention refers to medicine and describes a method for preparing a tablet exhibiting antihypertensive activity containing a) an active substance containing valsartan 80 or 160 mg or its pharmaceutically acceptable salt, and hydrochlorothiazide (HCTZ) 12.5 or 25 mg; b) pharmaceutical acceptable additives suitable for preparing tablets by compression wherein said method involves the stages, I) grinding of the active substance which contains said valsartan and said hydrochlorothiazide, and pharmaceutically acceptable additives; II) compression of a mixture of the grinded active substance and additives with making a comprimate with said compression for making the comprimate requires compaction of the dry mixture of the grinded ingredients; III) transformation of the comprimate into a granulate having a particle size distribution 9 to 340 micron; and IV) compression of the granulate with preparing the tablet.

EFFECT: method provides preparing the tablet possessing intensified antihypertensive activity.

4 cl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula , which is a methylhydrofumarate (MHF) prodrug. In formula (I), radicals and symbols have the values specified in the patent claim. The invention also refers to a pharmaceutical composition containing the declared methylhydrofumarate drugs, to using the declared methylhydrofumarate drugs and the pharmaceutical composition containing them, for treating diseases, such as psoriasis, asthma, multiple sclerosis, inflammatory intestinal disease and arthritis, and to a method of treating the above diseases.

EFFECT: higher oral bioavailability and plasma MHF, dimethylfumarate and/or other metabolites.

47 cl, 1 tbl, 54 ex

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