Method for treatment of arterial hypertension

FIELD: medicine, therapy.

SUBSTANCE: invention relates to a method for treatment of arterial hypertension. Method involves administration of one or some medicinal preparations in biorhythmical sequence taken among the following order: papaverin, common wormwood tincture - at 7.00 - 9.00 a. m.; thrombo-ACC, rheopro, clopidogrel - at 9.00 - 11.00 a. m.; No-Spa - at 11.00 a. m.; trental - at 11.15 a. m.; atenolol, propranolol, metoprolol, nifedipin, verapamil, cordaron, valerian, motherwort - at 11.30 a. m.; polyvitamins, fenules - at 1.00 p. m.; No-Spa - at 4.00 p. m.; trental - at 4.15 p. m.; hypothiazid, furosemid, verospiron, captopril, enalapril, prestarium, quinapril, ramipril, losartan, valsartan - at 4.30 p. m.; No-Spa - at 7.00 p. m.; trental - at 7.15 p. m.; atenolol, propranolol, metoprolol, nifedipin, verapamil, cardura, valerian, motherwort, phenazepam, coaxil, paxil - at 7.30 p. m.; ginseng - at 9.00 p. m.; Essentiale, simvastatin, lovastatin - at 11.00 p. m. Method provides recovery of levels synchronization in organization of organ-forming systems that allows carrying out the effect on the arterial pressure value in the corresponding time of day.

EFFECT: improved treatment method.

1 tbl, 2 dwg, 1 ex

 

The invention relates to medicine, in particular to therapy, and may find application in the treatment of hypertension (hypertension).

Arterial hypertension (AH) is one of the most pressing problems therapy. Currently in the world 30% of the population (about 1580 million people have high blood pressure (BP). The results Remengesau research out of every thousand people who have recorded increased AD 10 developing heart failure (CH), approximately 30 million people [14, 16].

In Russia 2 million 682 thousand people, 39.2% of men and 41.1% of women have an increased level of HELL. You know about their disease and 37.1 58.0%, respectively, treated only 21.6 and 45.7%, and treated effectively only 5.7 and 17.5%. For comparison, effectively treated in the U.S., 27% of patients with hypertension, France - 24%, in Canada - 22%, Italy 9%, Egypt - 8%, UK 6%, China 3% Poland 2% [11-13]. Most authors consider AG as one of the key factors for ischemic and hemorrhagic stroke, ischemic heart disease (IHD), the development of cardiac and renal failure. It should be noted that over the past two decades, Russia became one of the first places in Europe in mortality from coronary heart disease and strokes in the brain. And are more likely to suffer hypertension and more likely to die men of tragopogon the third age - to 55 years [14]. In our country among males 45-74 years of age for ischemic heart disease and stroke account for 87.5% of deaths from cardiovascular diseases (40.8% of the total mortality), in women of the same age, the figures are 85% (45.4%), respectively [4].

Based AG lies disruption of normal neurogenic and/or humoral regulation of vascular tone with the gradual formation of organic changes in the heart and vasculature, which undoubtedly contributes to the atherosclerotic process [7]. The basis of atherosclerosis, damaging vital organs, lies dyslipidemia characterized by high levels proatherogenic lipids (cholesterol low density lipoprotein - LDL, triglycerides) and low levels of atherogenic cholesterol high density lipoprotein (HDL) [5].

It cannot be denied that for AG, as with most diseases, the clinical picture is determined by a number of functional disorders which are caused by the reflex disorders with reversible, and it is logical for correction of these violations to use methods based on the principles of reflexology. The most developed section of acupuncture traditional acupuncture is based on three major theoretical positions[2, 5, 10]:

1. In humans it is necessary to distinguish 12 "main bodies": the light", "large intestine, stomach, spleen and pancreas", "heart", "small intestine", "bladder", "kidney", "pericardium", "three models", "gallbladder", "liver".

2. "Main bodies" in a healthy body come together in a system of complex interactions, giving each other a stimulating and inhibiting effects (figure 1).

3. During the day each of 12 "main bodies" has a 2-hour interval of time the dominant functional activity in a strictly logical sequence (figure 2). During these hours the so-called "vegetative solo authorities have the greatest sensitivity to both pathogenic and therapeutic effects.

Functional daily cycles day-to-day energy constant in complete clinical health (clear daily biological rhythms of the major functional systems is the main condition of homeostasis, and thus imply the stability of the weight, HELL, etc). Rhythm functional activity (one of the most important characteristics of a living system) ensures the stability of periodic replacement of "functioning" and "resting" units (biological quanta) in a certain sequence. Periodic processes are needed to achieve the ideal state to which tremeda all biological systems - maximum efficiency with minimum energy consumption.

Physiological parameters react differently to different effects depending on what phase (point) biological rhythm it is. In the course of evolution humans have developed a control system of rhythmic processes play the main role in which, in the modern view, given the hypothalamus [1, 3, 16]. From the standpoint of modern neurophysiology "main bodies" vegetative manageable, their interaction also due to vegetative and, ultimately, determined by the hypothalamus and associated with him in the structures of the Central nervous system (CNS). The hypothalamus monitors the state of the internal environment of the body, supporting the most important biochemical, hormonal, and other parameters of homeostasis within normal values.

You cannot deny the importance of feedbacks: if the hypothalamus regulates the normal functioning of internal organs, then, obviously, through a system of feedbacks internal organs determine the normal functioning of the hypothalamus [8].

Knowing about the global role of biological rhythms in determining the state of health of the body, you must agree that "ill health", and the more the disease should occur primarily desynchronosis - violations is s biorhythms, changes the energy of the constancy of the cyclicity of the major functional systems (usually in the direction of increasing cost - entropy).

Clinically the state of desynchronization can occur from light prodromov to gross violations of biorhythms basic life functions (e.g., increased AD).

Held in the world population-based studies (MUSIC, FACET, TOR-1, TAIM, TOMHS and others) have demonstrated the importance of effective treatment of hypertension to reduce the risk of cardiovascular events (CVE) and mortality. It is proved that the decline in diastolic blood pressure (DBP) only 2 mm Hg leads to a reduction in the incidence of stroke by 15%, CHD - 6% [11].

Known methods of treatment of hypertension, antihypertensive therapy, are intended to reduce high blood pressure to "target": for patients young and middle aged up to 130/85 mmHg for the elderly - up to 140/90 mm rtrt. [9].

Are the main classes of drugs (diuretics, beta-blockers, calcium antagonists, angiotensin converting enzyme (ACE)inhibitors, antagonists angiotensinogen receptors, alpha-blockers). Monotherapy provides a reduction in systolic blood pressure (SBP) on average 3-7 mm Hg and DBP - 4-8 mm Hg According to the study NOTES, reduce the blood pressure to normal values when monotherapy fails to achieve only is about 30% of patients [11, 18]. The ineffectiveness of the "average" dose of the drug is the preferred destination of the combined forms of antihypertensive drugs, containing one tablet two drugs, prolonged forms of antihypertensive drugs [9, 15].

The disadvantages of modern principles of drug therapy (figuratively speaking, one tablet three times a day") are "expensive" effects on the body (original flawed (the patient) the system must operate with the same load during the day), the depletion of the functionality of the affected organ, the need to increase dosage over time, the transition of the pathological process in the chronic with the outcome in decompensation and structural changes in organs and tissues, often unwanted side effects.

Studies of circadian blood pressure profile showed pronounced variability of the values of HELL. The use of both invasive and non-invasive monitoring of HELL has allowed to identify the patterns of fluctuations of blood pressure during the day. Reminesce epidemiological study showed that the time of maximum risk for sudden cardiac death accounts for the morning (7.00 am to 9.00 h), the minimum risk for the period from 9.00 till 13.00 o'clock the Risk of sudden death in the early morning hours on average 70% higher compared to the rest period of the day [18]. Viewlanguage, the peak development of stroke, ischemic and hemorrhagic, falls in the morning (between 8.00 and 12.00 am). The incidence of myocardial infarction in all groups examined (young, old, women and men with a previous history of coronary artery disease and no history of CHD) also has a peak in the morning hours. In the period from 6.00 am to 12.00 am observed a sharp rise in blood pressure, increased vascular tone, which coincide with neurohumoral changes. This time is also the only period during the day, when observed increased platelet aggregation, hypercoagulation and reduced fibrinolytic activity. In patients with stable angina to 40% of episodes of painful and painless myocardial ischemia accounts for the period from 6.00 am to 12.00 h and is 46% of the total time of ischemia per day [17].

Our study with regard to data analysis of daily monitoring AD (Smad) in patients with arterial hypertension revealed a pronounced variability of the values of HELL during the day for time intervals of activity of the major functional systems.

The objective of the invention is to increase the effectiveness of treatment, the reduction of side effects of drugs, decrease doses of basic drugs.

This problem is solved by the method lies in the fact that injected into the biorhythmic on what sledovatelnot one or more drugs, selected from the range: 7.00-9.00 - papaverine, tincture of wormwood; 9.00-11.00 - trombas, reopro, clopidogrel; 11.00 - but-Spa, 11.15 - trental, 11.30 - atenolol, propranolol, metoprolol, nifedipine, verapamil, cordarone, Valerian, motherwort; 13.00 - multivitamin, phenyls; 16.00 - no-Spa, 16.15 - trental at 16.30 - gipotiazid, furosemide, verospiron, captopril, enalapril, Prestarium, quinapril, ramipril, losartan, valsartan; at 19.00 - no-Spa, 19.15 - trental at 19.30 - atenolol, propranol, metoprolol, nifedipine, verapamil, xatral, valerina, motherwort, phenazepam, coaxil, paxil; 21.00 - ginseng; 23.00 - Essentiale, simvastatin, lovastatin.

Biorhythmic pharmacotherapy (BRFT) involves the implementation of therapeutic effect of phylogenetically determined the levels of organization of ORGANOARSENIC systems ("main bodies" - the hypothalamus and associated structures of the CNS, including the vasomotor center of the medulla oblongata "main bodies"), primarily vascular component that allows you to change in the right direction mode of the vascular support, and thus to influence the level of blood pressure at an appropriate time of day.

Methods of administration of drugs similar to traditional (intravenously, intramuscularly, orally).

BRFT carried out so that the most affected functional system done is make the impact of a specific genotype ("basic") drugs in therapeutic dose (from minimum to shock), on the other functional systems, the impact is subtherapeutic ("signal") doses genotype drugs (these doses can be 4-10 times less than the minimum therapeutic). As the formation of the sustainability of daily biological rhythms of the major functional systems of the dose to the basic drugs under control of Smad steadily reduced to "signal".

In order to prevent desynchronosis BRFT is only "signal" doses of drugs.

To illustrate the effectiveness of the proposed method given clinical case.

Patient B., 50 years, was under observation with a diagnosis of:

Hypertension III Art. Re ischemic stroke in the basin of the right middle cerebral artery in ischemic type from 26.02.2003. Encephalopathy. Hyperlipidemia 4 types. Widespread osteochondrosis of spine, posterior protrusion of the intervertebral discs in the cervical spine. Primary antiphospholipid syndrome. Primary varicose superficial veins of the lower extremities.

State to BRFT:

- raising HELL up 230/140 mm Hg, accompanied by headache, nausea, flashing "flies" before the eyes;

the feeling of numbness in the left half of the body, which arose on the fo is e high blood pressure (160/100 mm Hg);

- dizziness when changing body position. From the anamnesis:

- Since 1972, is often a headache, sometimes accompanied by vomiting.

In 1989 registered for the first time raising HELL to 180/100 mm Hg, accompanied by a feeling of "numbness" in the left half of the body. Outpatient status is regarded as hypertension, recommended: receiving clonidine 1-2 table. daily; against this background, with a frequency of 1-2 times a month there was an increase of HELL up to 200/100 mm Hg, accompanied by headache, nausea, flashing "flies" before the eyes, kupirovalsa additional admission clonidine, Dibazol, papaverine. In the future independently stopped taking clonidine.

- In 2001, with the emotional strain had a feeling of "numbness" in the left half of the body, while increasing the HELL up 230/140 mm Hg At admission condition regarded as acute ischemic stroke (cerebral vascular accident) in the pool right middle cerebral artery in ischemic type, were treated with aminophylline, answered; in the future for a long time (about 6 months) continued weakness, a feeling of "insecurity" in the left hand, arm, leg.

In September 2002, again with increased physical and emotional stress had a feeling of "numbness" in the left half of the body when raising HELL. With them to reach the implementation of the state is regarded as Hypertension III senior State after a cerebral vascular accident in 2001, Atherosclerosis of the aorta, cerebral arteries. Dyscirculatory encephalopathy II Art. by magnetic resonance imaging (MRI) brain data for volumetric process is not obtained. Conducted therapy nebilet 5 mg/s, arifona-retard 1.5 mg/s, Prestarium 4 mg/day, clonazepam 0,5 mg, piracetam, Cavinton, trombas 100 mg/S. against this background, the AD was 120-110/70-60 mm Art. RT

In January 2003, in connection with the high cost stopped taking nebilet.

- 26.02.2003 increased physical and emotional stress had a feeling of "numbness" in the left half of the body, General weakness, temporary loss of speech when raising HELL to 160/100 mm Hg At admission condition is regarded as Hypertension III Art. Re ischemic stroke in the basin of the right middle cerebral artery in ischemic type from 26.02.2003. Encephalopathy. Hyperlipidemia 4 types. Widespread osteochondrosis of spine, posterior protrusion of the intervertebral discs in the cervical spine. Primary varicose superficial veins of the lower extremities. Conducted therapy:

- atenolol 1 t (50 mg) in the morning, 1 so at night,

- Prestarium 1 so (4 mg) in the morning,

- gipotiazid 1 t(25 mg) in the morning,

- Fraxiparine 0.6 ml 2 times a day subcutaneously,

- trabass 1 so(100 mg) ut the Ohm

- /drip R-ry trental, pyracetam, Cavinton.

Against this background, the patient's condition improved slightly, but continued weakness in his left hand, foot, headache in the occipital region, the feeling of "heaviness" in my head. When checking BP levels in the morning and in the evening was still raising HELL to 150-170/85-100 mm Hg During examination: HELL 160/90 mm Hg rhythmic heart sounds, heart rate 95/min Tenderness paravertebral points C6-Th8. Superficial varicose veins of the lower extremities.

When performing clinical laboratory tests in the lipid spectrum was rising triglycerides up to 209 mg/DL (N 50-150), very low density lipoprotein (VLDL) - up to 41.8 mg/DL (N 10-30), reduced HDL up to 32 mg/DL (N 35-75); haemoglobin rate was 4.8 (N 1.2-4.2); the type of hyperlipidemia 4. When conducting ultrasound abdomen showed signs of fatty liver, disformity gallbladder. When the ECHO-KG revealed minor signs of left ventricular hypertrophy (thickness of the posterior wall of the left ventricle in diastole 1.2 cm (with N up to 1.1 cm). The patient was examined by an oculist, a condition regarded as hypertensive angiopathy of the retina.

BRFT was carried out under the control of Smad with the analysis of the obtained data by time intervals daily functional activity of the major functional with the system (the average GARDEN - SSD, average DBP-SDAD, average AD - GARDEN).

Source to destination BRFT (atenolol ½ so(50 mg) in the morning and ½ so in the evening, Prestarium 1 so(4 mg) in the morning, gipotiazid 1 t(25 mg) in the morning) SSAD total amounted to 120 mm Hg, SDAD total - 80 mm Hg, GARDEN total - 95 mm Hg At the level of the AD was:

- 7.00-9.00 - 115/70-130/80 mm Hg,

- 9.00-11.00 - 105/75-150/90 mm Hg,

- 11.00-13.00 - 120/90-140/105 mm Hg,

- 13.00-15.00 - 130/90-170/100 mm Hg,

- 15.00-19.00 - 110/90-150/100 mm Hg,

- 19.00-21.00 - 125/75-140/90 mm Hg,

- 23.00-3.00 - 95/60-120/80 mm Hg

When conducting BRFT initial daily dose of basic drugs were reduced in 2 times (daily dose of atenolol is 50 mg, hypothiazid up to 12.5 mg, Prestarium - up to 2 mg).

BRFT was conducted according to the following scheme: for action: on the functional system of the stomach (7.00-9.00) was administered papaverine 1 so (40 mg) at 7.00-9.00; on the functional system of the spleen-pancreas (9.00-11.00) - trabass 1 so (100 mg); on the functional system of the heart (11.00-13.00)- but-Spa 1/2 t 11.00, trental 1/4 tons(100 mg) at 11.15 atenolol 1/2 tons(50 mg), Valerian 1 jar - 11.30; functional system of the small intestine (13.00-15.00) - multivitamin 1 tablet at 13.00; urinary system (bladder 15.00-17.00, kidney 17.00-19.00) - but-Spa 1/2 T. - 16.00, trental 1/4 tons(100 mg) at 16.15, gipotiazid 1/2 so(25 mg), Prestarium 1/2 so(4 mg) at 16.30; functional system pericardium (19.00-21.00) - but-Spa 1/t at 19.00, trental 1/4 tons(100 mg) at 19.15, atenolol 1/4 T.(50 mg), Valerian 1 jar - 19.30; biliary system (gallbladder 23.00-01.00, liver 01.00-03.00) - Essentiale 1 so at 23.00.

On the 7th day BRFT the patient noted improvement of health, reduction of blood pressure with self-control blood pressure 3 times a day before 145-135/85-75 mm Hg

On the 14th day BRFT under the control of Smad noted improvement in several indicators: SAD total was 110 mm Hg, SDAD total - 70 mm Hg, GARDEN total - 85 mm Hg While the AD was:

- 7.00-9.00 - 100/60-130/80 mm Hg,

- 9.00-11.00 - 100 / 80g-140/80 mm Hg,

- 11.00-13.00 - 110/85-125/95 mm Hg,

- 13.00-15.00 - 110/75-150/90 mm Hg,

- 15.00-19.00 - 105/75-140/95 mm Hg,

- 19.00-21.00 - 105/65-130/80 mm Hg,

- 23.00-3.00 - 80/45-110/70 mm Art. RT

On the 14th day BRFT were reduced daily dose of atenolol, hypothiazid and Prestarium (dose atenolol 25 mg, hypothiazid - up to 6.25 mg, Prestarium up to 1 mg), the other drugs were given in the previous daily dose.

On the 21st day comprehensive BRFT the patient noted significant improvement in overall health: normalized night's sleep, has ceased to disturb the feeling of "numbness" in the left half of the body.

On the 28th day BRFT in the blood decreased triglycerides up to 195 mg/DL, VLDL - up to 38.5 mg/DL increase in HDL to 43.

On the 28th day BRFT when conducting Smad SAD total was 115 mm RTS is., SDAD total - 70 mm Hg, GARDEN total - 85 mm Hg While the AD was:

- 7.00-9.00 - 100/75-130/85 mm Hg,

- 9.00-11.00 - 110/75-140/90 mm Hg,

- 11.00-13.00 - 120/90-150/90 mm Hg,

- 13.00-15.00 - 90/70-120/80 mm Hg,

- 15.00-19.00 - 100/60-135/90 mm Hg,

- 19.00-21.00 - 105/60-130/85 mm Hg,

- 23.00-3.00 - 95/50-120/75 mm Hg

On the 28th day BRFT were reduced daily dose of atenolol and hypothiazid (dose atenolol - up to 18.75 mg, hypothiazid up to 3.125 mg), all other drugs were given in the previous daily dose.

On the 56th day BRFT when conducting Smad SAD total was 110 mm Hg, SDAD total - 70 mm Hg, GARDEN total - 80 mm Hg When the AD was:

- 7.00-9.00 - 110/60-115/70 mm Hg,

- 9.00-11.00 - 110/70-120/80 mm Hg,

- 11.00-13.00 - 105/80-130/80 mm Hg,

- 13.00-15.00 - 105/65-130/85 mm Hg,

- 15.00-19.00 - 90/55-140/90 mm Hg,

- 19.00-21.00 - 100/70-160/80 mm Hg,

- 23.00-3.00 - 75/40-105/75 mm Hg

On the 56th day BRFT has been reduced daily dose of atenolol to 12.5 mg, gipotiazid was administered 3.125 mg every other day; all other drugs were given in the previous daily dose.

These Smad in the dynamics (the original traditional antihypertensive therapy on the background of BRPT) presented in the table.

Table 1.

Clinical trials of the proposed method showed its higher therapeutic efficacy compared with monotherapy, the purpose of the combined and extended-release forms of antihypertensive drugs and no side effects. BRFT allows you to "significantly" reduce the daily dose "basic" antihypertensive drugs (atenolol, Prestarium, hypothiazid).

References

1. Anokhin P.K. Essays on physiology of functional systems. - M.: Medicine, 1978 - 447 S.

2. Vohralik VG, Vohralik MV Acupuncture (punctation reflexology). Bitter, 1978 - 296 S.

3. Dillman NR. Endocrinology Oncology. - L.: Medicine, 1983 - 408 S.

4. Dmitriev V.V. et al. Isolated systolic hypertension. - M.: Consilium medicwn. Application: hypertension, 2001 - p.19-25.

5. Kuzin A.I. et al. Arterial hypertension and diabetes mellitus type 2 in patients with metabolic syndrome: effects on lipid profile. - M: Arterial hypertension, 2003; v.9, No. 9 - p.67-68.

6. Luvsan, Traditional and modern aspects of Oriental medicine. - M, 2000 - 400 C.

7. Makolkin V., Ovcharenko SR Internal diseases. - M.: Medicine, 1999 - 592 S.

8. National guidelines for the diagnosis and treatment of hypertension. All-Russian scientific society of cardiology (GFCF), section arter what happens hypertension. - M.: Consilium medicum. Application: hypertension, 2001 - p.3-11.

9. Tareeva D.M. Guide to acupuncture. - M.: Medicine, 1980 - 560 C.

10. Chazova I.E. Modern approaches to the treatment of arterial hypertension. - M.: Consilium medicum. Application: hypertension, 2001 - page 11-19.

11. Chazova I.E. the First results of the study BASSOON. - M.: Consilium medicum, 2002; v.4, No. 11 - C.

12. Chazova I.E. Combination therapy of hypertension moderate and severe course. - M.: Consilium medicum, 2003; V.5, №5 - s.

13. Yurenev A.P., G.P. Arutyunov et al. Survival and quality of life of patients with cardiovascular diseases. - M.: breast cancer according to the materials of the VIII Russian national Congress "Man and medicine", 2001; v.9, No. 12 - s-523.

14. Guidelines for the management of arterial hypertension. ESH-ESC Guidelines Committee, 2003.

15. F. Halberg castle et al. Chronobiologie optimisation of aging. Aging and Biol. Rhyt. Conf. Spons Florida Apr. 13-15, 1977, New York, London, Plecnum Press, 1978; 5-56.

16. Kapiotis S. et al. Morning hypercoagulability and hypofibrmolysis: diurnal variations in circulating activated factor VII, protrombin fragment Fl+2, and plasmin-plasmin inhibitor complex. Circulation 1997; 96: 19-21.

17. The HOT Study Group. The Hypertension Optimal Treatment Study (the HOT Study). Blood Pressure, 1993; 2; 62-68.

18. Willich S.N. et al. Circadian variation in the incidence of sudden cardiac death in the Framingam Heart Study population. Am J Cardiol 1987; 60: 801-806.

A method of treating hypertension, characterized in that designate biorhythmic sequence of one or more drugs is selected from the range: 7.00-9.00 - papaverine, tincture of wormwood; 9.00-11.00 - trombas, reopro, clopidogel; 11.00 - but-Spa, 11.15 - trental, 11.30 - atenolol, propranolol, metoprolol, nifedipine, verapamil, cordarone, Valerian, motherwort; 13.00 - multivitamin, phenyls; 16.00 - no-Spa, 16.15 - trental at 16.30 - gipotiazid, furosemide, verospiron, captopril, enalapril, Prestarium, quinapril, ramipril, losartan, valsartan; 19.00 - no-Spa, 19.15 - trental in 19.30 - atenolol, propranol, metoprolol, nifedipine, verapamil, xatral, Valerian, motherwort, phenazepam, coaxil, paxil; 21.00 - ginseng; 23.00 - Essentiale, simvastatin, lovastatin.



 

Same patents:

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to a combined medicinal agent used in treatment of arterial hypertension. The proposed agent comprises the combination of enalapril maleate and hydrochlorothiazide as an active component, and also sodium hydrocarbonate, starch, lactose, iron oxide and stearate as accessory substances. The proposed agent is stable in storage and releases the active component easily.

EFFECT: improved and valuable properties of agent.

8 cl, 1 tbl, 5 ex

FIELD: medicine, cardiology.

SUBSTANCE: in addition to traditional treatment with broncholytics it is necessary to apply analapryl at increasing dosages starting from 2.5 up to 10 mg/d, therapy course lasts for 24 d. Due to anti-ischemic action of analapryl the development of bronchospasm has been excluded.

EFFECT: higher efficiency of therapy.

3 ex, 1 tbl

FIELD: organic chemistry, chemical technology, medicine.

SUBSTANCE: invention relates to a new compound - 2-hydroxy-5,5-dimethyl-4-oxo-2-hexenoic acid N-41-methyl-21-pyridylamide of the formula:

. This compound is prepared by interaction of 2-hydroxy-5,5-dimethyl-4-oxo-2-hexenoic acid with 4-methyl-2-pyridylamine. Proposed compound can be used in medicine as a hypertensive agent. The hypertensive activity of this compound exceeds activity of standard compound - midodrine hydrochloride by 2-fold increase of arterial pressure value and by 3-fold by duration effect in combination with 2-fold reduced toxicity.

EFFECT: improved and valuable medicinal properties of compound.

1 cl, 2 tbl, 1 ex

FIELD: organic chemistry, chemical technology, medicine.

SUBSTANCE: invention relates to new derivatives of pyrrolopyrimidine of the formula (1) and their pharmaceutically acceptable salts possessing properties of selective inhibitor of specific cyclic guanosine 3',5'-monophosphate phosphodiesterase (specific cGMP PDE) (PDE V). In the formula (1) R1 represents hydrogen atom (H), (C1-C3)-alkyl substituted optionally with one or some fluorine atoms; R2 represents H, halogen atom, (C1-C6)-alkyl substituted optionally with hydroxyl group (-OH), (C1-C3)-alkoxy-group, (C3-C6)-cycloalkyl or one or some fluorine atoms, (C3-C6)-cycloalkyl; R3 represents (C1-C6)-alkyl substituted optionally with (C3-C6)-cycloalkyl or one or some fluorine atoms; R4 represents (C1-C6)-alkyl substituted optionally with one or some fluorine atoms; R5 represents -SO2NR6R, -NHSO2R8 or heterocyclyl such as tetrazolyl; each R6 and R7 represents independently H or (C1-C6)-alkyl substituted optionally with -CO2H or one or some fluorine atoms; or in common with nitrogen atom to which they are bound form monocylic ring, such as imidazole, pyrrolidine, piperidine, morpholine, piperazine and homopiperazine wherein indicated group is replaced optionally with R9 wherein R9 represents (C1-C6)-alkyl substituted optionally with one or some halogen atoms, hydroxyl group (OH), (C1-C3)-alkoxy-group that is replaced optionally with one or some fluorine atoms, -NR11R12, -C=NR13(NR14R15) or tetrazolyl group, 6-membered nitrogen-containing heteroaryl group; each R11 and R12 represents independently H or (C1-C4)-alkyl; R13represents H; each R14 and R15 represents independently H. Also, invention relates to intermediate compounds, methods for preparing compounds and pharmaceutical compositions. Proposed compounds can be used in treatment of impotency, sexual dysfunction in females, stable, nonstable and variant (Prinzmental) stenocardia and other diseases also.

EFFECT: improved preparing method, valuable medicinal properties of compounds.

15 cl, 1 tbl, 250 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a pharmaceutical composition used in treatment or prophylaxis of hypertension, heart diseases, vascular disorders and kidney diseases. The composition comprises compound of the formula (1) as antagonist of angiotensin II receptors and one or some diuretics. The composition shows enhanced effectiveness.

EFFECT: valuable medicinal properties of composition.

23 cl, 2 tbl, 1 ex

FIELD: organic chemistry, vitamins, medicine, pharmacy.

SUBSTANCE: invention relates to a new compound of the formula (I): wherein X means hydrogen atom or hydroxy group; R1 and R2 that can be similar or different mean hydrogen atom, (C1-C4)-alkyl; R3 means hydrogen atom, methyl group, fluorine or chlorine atom. Also, invention relates to its esters able to hydrolysis in vivo in combination with pharmaceutically acceptable acids. Also, invention relates to a pharmaceutical composition eliciting the inhibitory activity with respect to proliferation and promoting differentiation of cells and comprising the effective dose of compound of the formula (I) in common with pharmaceutically acceptable carriers and/or excipients. Also, invention relates to applying compound of the formula (I) for preparing a medicine used in treatment and prophylaxis of disease characterizing by abnormal differentiation of cells and/or proliferation of cells.

EFFECT: valuable medicinal properties of compounds.

13 cl, 3 sch, 3 tbl, 6 ex

FIELD: medicine, chemical-pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to a solid medicinal formulation eliciting an antihypertensive, anti-anginal, vasodilating, antioxidant and antiproliferative effect. The solid medicinal formulation comprises the following components: carvedilol, disaccharide, magnesium stearate, starch, calcium phosphate, hydroxypropylmethylcellulose, aerosil and carboxymethylcellulose sodium salt. Also, invention discloses a method for preparing this formulation. Invention provides preparing the formulation eliciting high rate and fullness in releasing an active substance in the human body, stability of quality indices for all fitness period and allowing the effective usage in manufacturing the medicinal agent. Invention can be used in treatment hypertension, stenocardia, myocardium ischemia and chronic cardiac insufficiency.

EFFECT: improved preparing method, valuable medicinal properties of formulation.

5 cl, 1 tbl, 4 ex

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention relates to new substituted derivatives of norbornylamine with exo-configuration of nitrogen atom and endo-anellated 5-6-membered cycles of the formula (I) and with exo-configuration of nitrogen atom and exo-anellated 5-6-membered cycles of the formula (Ia) , and their pharmaceutically acceptable salts or trifluoroacetates also. In compounds of the formula (I) or (Ia) A means (C1-C4)-alkylene; S1 means optionally (C1-C4)-alkyl; S2 means (C1-C4)-alkyl or hydrogen atom (H) being if S1 and S2 mean alkyl then X in the group [-N+(S1S2)-X-] corresponds to pharmacologically acceptable anion or trifluoroacetate; B means saturated or unsaturated carbon 5- or 6-membered cycle; R1, R2, R3, R4 and R5 have values given in the description. Also, invention relates to a method for preparing these compounds and to a medicinal agent. These compounds can be used for preparing medicinal agents useful for treatment or prophylaxis in breathing impulse disturbance, in particular, in breathing disturbance caused by sleep, transient breathing stop during sleep, snore, for treatment or prophylaxis of acute and chronic renal diseases, in particular, acute and chronic renal insufficiency and, disturbance in intestine, gallbladder, ischemic states of peripheral and central nervous system disturbances, severe attacks and others symptoms. Compounds are inhibitors of sodium-proton exchange, show effect on serum lipoprotein and therefore they can be used in prophylaxis and regression of atherosclerotic alterations.

EFFECT: improved preparing method, valuable medicinal properties of compounds.

21 cl, 70 ex

FIELD: medicine.

SUBSTANCE: vaccine is high molecular weight protein conjugate with angiotensine II taken in high molecular weight protein : angiotensine II proportion of 1:12-55 in % by weight. The conjugate is modified with equilibrium quantity of immunocompetent polyelectrolyte like polyoxydonium.

EFFECT: stable physiological response within prolonged period of 6-12 months.

3 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a prophylactic or therapeutic agent used against hyperlipidemia and comprising as an active component the heterocyclic compound of the formula [1]:

or its pharmaceutically acceptable salt wherein R1 represents aryl optionally substituted with similar or different one-three groups taken among alkyl, halogenalkyl, trihalogen alkyl, alkoxy-group and halogen atom; Het represents bivalent aromatic heterocyclic group of the formula [5]:

wherein X represents oxygen, sulfur atom or NR6 wherein R6 represents hydrogen atom or alkyl; R2 represents hydrogen atom, alkyl or trihalogenalkyl; D represents alkylene and alkenylene; E represents group of the formulae [3] or [4] wherein Y represents oxygen or sulfur atom; R3 and R4 are similar or different and each represents hydrogen atom or alkyl; p = 1; Z represents carboxy-group, alkoxycarbonyl, cyano-group or 1H-5-tetrazolyl. Also, invention relates to new compounds belonging to group of above enumerated heterocyclic compounds of the formula [1] that show effect reducing blood triglycerides level, low density lipoprotein cholesterol, glucose and insulin or effect enhancing high density lipoprotein cholesterol and effect reducing the atherogenic effect. Therefore, these compounds can be used in prophylaxis or treatment of hyperlipidemia, arteriosclerosis, heart ischemic disease, brain infarction, rheocclusion after percutaneous intraluminal coronary angioplasty, diabetes mellitus and obesity.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

29 cl, 1 tbl, 170 ex

FIELD: stockraising.

SUBSTANCE: claimed method includes daily animal airing and feeding of propylene glycol two times per day for 10 days. Before feeding animals are aired for two hours. Before propylene glycol addition into compound feed in amount of 225-450 g per beast it is mixed with antiketosis premix containing 200 g of grass meal, 200 g of sunflower oilcake, 150 g of wheal bolting, 0.5 g of 50 % vitamin E, 500000 IU of vitamin A and 100000 IU of vitamin D, which is fed in dose of 600 g/beast per day. Mixture of propylene glycol and premix is fed on morning and evening in half daily dose with main ration, having balanced sugar/protein ratio of 1.5:1-2:1, respectively. In the first 3-4 days after ketosis detection total ration food value is decreased by 20-50 %, then during 5 days food value is gradually increased to normal one.

EFFECT: effective method for prophylaxis and treatment of cow milk fever.

2 cl, 1 tbl, 1 ex

FIELD: organic chemistry, antibiotics, pharmacy.

SUBSTANCE: invention relates to 9a-N-[N'-(phenylsulfonyl)carbamoyl]-derivatives of 9-deoxo-9-dihydro-9a-aza-9a-homoerythromycin A and 5-O-desosaminyl-9-deoxo-9-dihydro-9a-aza-9a-homoerythronolide A that are new semisynthetic macrolide antibiotics relating to class of azalides showing antibacterial effect and describing by the general formula (1):

wherein R1 means hydrogen atom (H), (C1-C4)-alkyl or halogen atom; R means H or cladinosyl radical, and to their pharmaceutically acceptable salts. Also, invention relates to a method for their preparing and a pharmaceutical composition based on thereof.

EFFECT: improved preparing method, valuable medicinal properties of derivatives.

16 cl, 2 tbl, 14 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to derivatives of 1,3,2-oxazaphosphacycloalkane of the general formula (I):

wherein Y represents oxygen atom (O) or sulfur atom (S); n = 1, 2, 3 or 4; X represents hydroxamic acid or carboxylic acid; R2 represents hydrogen atom, (C1-C8)-alkyl, (C2-C6)-alkenyl or aryl-(C0-C6)-alkyl, and to their salts, hydrates or solvates. Proposed compounds are inhibitors of matrix metalloproteinases taking part in tissue degradation that suggests the possibility for their using in the human therapy and veterinary.

EFFECT: valuable medicinal properties of compounds.

11 cl, 4 tbl, 242 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a polymorphic modification of 4-(3,4-dichlorophenyl)-2-[2-(4-methylpiperazin-1-yl)benzylidene]thiomorpholine-3-one citrate. Invention describes 4-(3,4-dichlorophenyl)-2-[2-(4-methylpiperazin-1-yl)benzylidene]thiomorpholine-3-one citrate of the formula:

. Also, invention describes a pharmaceutical composition possessing antagonistic activity with respect to serotonine-1D receptor (5-HT1D) comprising the compound by claim 1 and pharmaceutically acceptable carrier, and a method for treatment of hypertension, all forms of depression and other diseases in mammals comprising administration the therapeutically effective dose of compound by claim 1 in needing mammal. Invention provides citrate that is stable in solid state and compatible with excipients in preparing preparations of definite medicines.

EFFECT: improved and valuable pharmaceutical properties of salt.

12 cl, 5 dwg, 8 tbl, 1 ex

FIELD: organic chemistry of heterocyclic compounds, biochemistry.

SUBSTANCE: invention relates to new ortho-substituted and N-substituted indoles of the formula (α): or (β): or their pharmaceutically acceptable salts wherein Z1 represents -CR4 or nitrogen atom (N); R4 means hydrogen atom (H), (C1-C6)-alkyl comprising optionally oxygen atom (O) or nitrogen atom (N) possibly substituted with halogen atom, keto-group, 5-6-membered cycloaliphatic radical possibly comprising 1-2 oxygen atoms (O) or nitrogen atom (N); Z2 represents -CH or -CR wherein R means (C1-C6)-alkyl; R1 means compound of the formula: wherein X1 means -CO or its isostere; m = 0, 1; Y represents alkyl that can be substituted; or two Y form in common (C2-C3)-alkylene; n = 0, 1 or 2; Z3 represents -CH; X2 represents -CH, -CH2 or their isostere; Ar represents one or two phenyl groups bound with X2 wherein phenyl can be substituted; R2 represents hydrogen atom (H), (C1-C6)-alkyl or aryl wherein each aryl comprises, possibly, oxygen atom (O) or nitrogen atom (N) and can be substituted. Proposed compounds are selective inhibitors of p38α kinase.

EFFECT: valuable biochemical properties of compounds.

34 cl, 5 tbl, 23 ex

FIELD: organic chemistry of heterocyclic compounds, biochemistry.

SUBSTANCE: invention relates to new ortho-substituted and N-substituted indoles of the formula (α): or (β): or their pharmaceutically acceptable salts wherein Z1 represents -CR4 or nitrogen atom (N); R4 means hydrogen atom (H), (C1-C6)-alkyl comprising optionally oxygen atom (O) or nitrogen atom (N) possibly substituted with halogen atom, keto-group, 5-6-membered cycloaliphatic radical possibly comprising 1-2 oxygen atoms (O) or nitrogen atom (N); Z2 represents -CH or -CR wherein R means (C1-C6)-alkyl; R1 means compound of the formula: wherein X1 means -CO or its isostere; m = 0, 1; Y represents alkyl that can be substituted; or two Y form in common (C2-C3)-alkylene; n = 0, 1 or 2; Z3 represents -CH; X2 represents -CH, -CH2 or their isostere; Ar represents one or two phenyl groups bound with X2 wherein phenyl can be substituted; R2 represents hydrogen atom (H), (C1-C6)-alkyl or aryl wherein each aryl comprises, possibly, oxygen atom (O) or nitrogen atom (N) and can be substituted. Proposed compounds are selective inhibitors of p38α kinase.

EFFECT: valuable biochemical properties of compounds.

34 cl, 5 tbl, 23 ex

FIELD: organic chemistry of heterocyclic compounds, biochemistry.

SUBSTANCE: invention relates to new ortho-substituted and N-substituted indoles of the formula (α): or (β): or their pharmaceutically acceptable salts wherein Z1 represents -CR4 or nitrogen atom (N); R4 means hydrogen atom (H), (C1-C6)-alkyl comprising optionally oxygen atom (O) or nitrogen atom (N) possibly substituted with halogen atom, keto-group, 5-6-membered cycloaliphatic radical possibly comprising 1-2 oxygen atoms (O) or nitrogen atom (N); Z2 represents -CH or -CR wherein R means (C1-C6)-alkyl; R1 means compound of the formula: wherein X1 means -CO or its isostere; m = 0, 1; Y represents alkyl that can be substituted; or two Y form in common (C2-C3)-alkylene; n = 0, 1 or 2; Z3 represents -CH; X2 represents -CH, -CH2 or their isostere; Ar represents one or two phenyl groups bound with X2 wherein phenyl can be substituted; R2 represents hydrogen atom (H), (C1-C6)-alkyl or aryl wherein each aryl comprises, possibly, oxygen atom (O) or nitrogen atom (N) and can be substituted. Proposed compounds are selective inhibitors of p38α kinase.

EFFECT: valuable biochemical properties of compounds.

34 cl, 5 tbl, 23 ex

FIELD: organic chemistry, medicinal virology, biochemistry, pharmacy.

SUBSTANCE: invention relates to derivatives of pyrazole of the formula (I-A):

wherein R1 means (C1-C12)-alkyl that can be optionally substituted with 1-3 substitutes taken among fluorine, chlorine and bromine atoms, (C3-C8)-cycloalkyl, phenyl, pyridyl or (C1-C4)-alkyl substituted with phenyl; R2' means optionally substituted phenyl wherein phenyl can be substituted with 1-2 substitutes taken among (C1-C4)-alkyl, (C1-C4)-alkoxyl, hydroxyl, fluorine, chlorine and bromine atoms, cyano- and nitro-group; R3 means (C1-C12)-alkyl or (C1-C4)-alkoxy-(C1-C4)-alkyl; A' means (C1-C4)-alkyl optionally substituted with phenyl or optionally substituted with 4-pyridyl wherein phenyl or 4-pyridyl can be substituted with 1-2 substitutes taken among (C1-C4)-alkyl, (C1-C4)-alkoxyl, hydroxyl, fluorine, chlorine and bromine atoms, cyano-group and NRR' wherein R and R' mean independently of one another hydrogen atom or (C1-C4)-alkyl; or A' means group of the formula CH2-U-heterocyclyl wherein U represents O, S or NR'' wherein R'' means hydrogen atom or (C1-C4)-alkyl and wherein heterocyclyl means pyridyl or pyrimidinyl that is optionally substituted with 1-2 substitutes taken among (C1-C4)-alkyl, fluorine, chlorine and bromine atoms, cyano-, nitro-group and NRR' wherein R and R' mean independently of one another hydrogen atom or (C1-C4)-alkyl; or A' means group of the formula CH(OH)-phenyl; or A' means the group CH=CHW wherein W means phenyl; X means S or O, and their pharmaceutically acceptable salts. These compounds are inhibitors of human immunodeficiency virus (HIV) reverse transcriptase and, therefore, can be used in treatment of HIV-mediated diseases. Also, invention relates to a pharmaceutical composition used in treatment of HIV-mediated diseases.

EFFECT: valuable medicinal properties of compounds and composition.

11 cl, 5 tbl, 32 ex

FIELD: organic chemistry, medicinal virology, biochemistry, pharmacy.

SUBSTANCE: invention relates to derivatives of pyrazole of the formula (I-A):

wherein R1 means (C1-C12)-alkyl that can be optionally substituted with 1-3 substitutes taken among fluorine, chlorine and bromine atoms, (C3-C8)-cycloalkyl, phenyl, pyridyl or (C1-C4)-alkyl substituted with phenyl; R2' means optionally substituted phenyl wherein phenyl can be substituted with 1-2 substitutes taken among (C1-C4)-alkyl, (C1-C4)-alkoxyl, hydroxyl, fluorine, chlorine and bromine atoms, cyano- and nitro-group; R3 means (C1-C12)-alkyl or (C1-C4)-alkoxy-(C1-C4)-alkyl; A' means (C1-C4)-alkyl optionally substituted with phenyl or optionally substituted with 4-pyridyl wherein phenyl or 4-pyridyl can be substituted with 1-2 substitutes taken among (C1-C4)-alkyl, (C1-C4)-alkoxyl, hydroxyl, fluorine, chlorine and bromine atoms, cyano-group and NRR' wherein R and R' mean independently of one another hydrogen atom or (C1-C4)-alkyl; or A' means group of the formula CH2-U-heterocyclyl wherein U represents O, S or NR'' wherein R'' means hydrogen atom or (C1-C4)-alkyl and wherein heterocyclyl means pyridyl or pyrimidinyl that is optionally substituted with 1-2 substitutes taken among (C1-C4)-alkyl, fluorine, chlorine and bromine atoms, cyano-, nitro-group and NRR' wherein R and R' mean independently of one another hydrogen atom or (C1-C4)-alkyl; or A' means group of the formula CH(OH)-phenyl; or A' means the group CH=CHW wherein W means phenyl; X means S or O, and their pharmaceutically acceptable salts. These compounds are inhibitors of human immunodeficiency virus (HIV) reverse transcriptase and, therefore, can be used in treatment of HIV-mediated diseases. Also, invention relates to a pharmaceutical composition used in treatment of HIV-mediated diseases.

EFFECT: valuable medicinal properties of compounds and composition.

11 cl, 5 tbl, 32 ex

FIELD: organic chemistry, medicinal virology, biochemistry, pharmacy.

SUBSTANCE: invention relates to derivatives of pyrazole of the formula (I-A):

wherein R1 means (C1-C12)-alkyl that can be optionally substituted with 1-3 substitutes taken among fluorine, chlorine and bromine atoms, (C3-C8)-cycloalkyl, phenyl, pyridyl or (C1-C4)-alkyl substituted with phenyl; R2' means optionally substituted phenyl wherein phenyl can be substituted with 1-2 substitutes taken among (C1-C4)-alkyl, (C1-C4)-alkoxyl, hydroxyl, fluorine, chlorine and bromine atoms, cyano- and nitro-group; R3 means (C1-C12)-alkyl or (C1-C4)-alkoxy-(C1-C4)-alkyl; A' means (C1-C4)-alkyl optionally substituted with phenyl or optionally substituted with 4-pyridyl wherein phenyl or 4-pyridyl can be substituted with 1-2 substitutes taken among (C1-C4)-alkyl, (C1-C4)-alkoxyl, hydroxyl, fluorine, chlorine and bromine atoms, cyano-group and NRR' wherein R and R' mean independently of one another hydrogen atom or (C1-C4)-alkyl; or A' means group of the formula CH2-U-heterocyclyl wherein U represents O, S or NR'' wherein R'' means hydrogen atom or (C1-C4)-alkyl and wherein heterocyclyl means pyridyl or pyrimidinyl that is optionally substituted with 1-2 substitutes taken among (C1-C4)-alkyl, fluorine, chlorine and bromine atoms, cyano-, nitro-group and NRR' wherein R and R' mean independently of one another hydrogen atom or (C1-C4)-alkyl; or A' means group of the formula CH(OH)-phenyl; or A' means the group CH=CHW wherein W means phenyl; X means S or O, and their pharmaceutically acceptable salts. These compounds are inhibitors of human immunodeficiency virus (HIV) reverse transcriptase and, therefore, can be used in treatment of HIV-mediated diseases. Also, invention relates to a pharmaceutical composition used in treatment of HIV-mediated diseases.

EFFECT: valuable medicinal properties of compounds and composition.

11 cl, 5 tbl, 32 ex

FIELD: medicine.

SUBSTANCE: method involves carrying out hernia removal in intralaminar way. Posterior longitudinal ligament defect is covered with Tacho-Comb plate after having done disk cavity curettage. Subcutaneous fat fragment on feeding pedicle is brought to dorsal surface of radix and dural sac.

EFFECT: enhanced effectiveness of treatment; reduced risk of traumatic complications.

1 dwg

Up!