Method of treating arterial hypertension

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine, namely, to therapy and cardiology, and deals with treatment of arterial hypertension. For this purpose into complex of conventional therapy additionally introduced is prostaglandin E2 in form of 0.0008% solution. Prostaglandin is introduced intravenously, starting with rate 50-100 ng/kg/min, increasing rate of introduction each 10 minutes on 20-40 ng/kg/min, bringing rate to 150-300 ng/kg/min during 40-60, minutes. Altogether there are three introductions per a course with 1-2 day intervals between them.

EFFECT: additional introduction of prostaglandin E2 in elaborated doses and regimen ensures efficient normalisation of arterial pressure during long term due to enhance of excretion of prostaglandins by kidneys, expressed vasodilation of vessels of kidneys, heart and brain, as well as normalisation of functional activity of platelets.

6 ex

 

The invention relates to medicine, specifically to methods of treatment of hypertension.

There is a method of treatment of hypertension, according to which the treatment is carried out dosed physical load, followed by additional introduction of sweatshop plant collection. The method provides a reduction in pressure due to excessive sweating, accompanied by release of chlorides (1 - Pat. Of the Russian Federation No. 2303431, MKI 6 AN 1/00, 2006). This method is adopted for the similar.

There is a method of treatment of heart failure (2 - Pat. Of the Russian Federation No. 2271197, MKI 6 AC 31/00, 2004). According to the method in sequence enter one or more drugs 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 at 19.30 - atenolol, propranol, metoprolol, nifedipine, verapamil, xatral, Valerian, motherwort, phenazepam, coaxil, paxil; 21.00 - ginseng; 23.00 - Essentiale, simvastatin, lovastatin. The method provides recovery when nchronization levels of organization of ORGANOARSENIC systems, that allows you to influence the level of blood pressure at an appropriate time of day. This method is adopted for the prototype.

However, the effectiveness of the prototype method in the treatment of hypertension is relatively limited.

The aim of the invention is to increase the efficiency of treatment of hypertension.

The technical result is achieved by the additional use of prostaglandin E2 in the form 0,0008% solution intravenously which shall, from a speed of 50-100 ng/kg/min, increasing the speed every 10 min 20-40 ng/kg/min, leading up to 150-300 ng/kg/min, for 40-60 min, and the rate was three prolonged injections with intervals of 1-2 days.

The method is implemented as follows.

Rats 9 months of age with spontaneous hypertension were registered HELL in the tail artery of rats bloodless method and noted the increase in blood pressure. Received treatment with prostaglandin E2 in the form 0,0008% solution intravenously which was performed from a speed of 50-100 ng/kg/min, increasing the speed every 10 min 20-40 ng/kg/min, leading up to 150-300 ng/kg/min, for 40-60 min, and the rate was three prolonged injections with intervals of 1-2 days. After 2.5 weeks after the course of injections of prostaglandin E2 p is avedano morphological study of the kidneys, Pia mater and myocardium. Prior to the introduction of prostaglandin E2 blood pressure in the studied rats were 168,5±4.8 mm RT. century, under the influence of the introduction of prostaglandin E2 decreased HELL to 141±2.6 mm RT. senior Dynamic study depressor reflex after infusion of prostaglandin E2 showed that the reflex was increased from -6,0 to -19 mm increased excretion of endogenous PG E2 kidneys from 4.5 to 4.9 ng/h Daily excretion of endogenous renal prostaglandin E2 after treatment was 8.5 ng/hour. The ratio of prostaglandin E2 to prostaglandin F2á increases from 0.56 to 0.63.

Morphologically, it was noted the plethora of glomerular and peritubular capillaries, the plethora juxtamedullary zone; in addition, it was expressed plethora microvascular infarction; plethora, and swelling of the soft meninges; the plethora intracerebrally vessels.

Infusion of exogenous prostaglandin E2 resulted in a high, persistent for several months, the decrease in systemic blood pressure, a significant strengthening of the depressor reflex and increase excretion of endogenous renal prostaglandin E2, as well as pronounced vasodilation of blood vessels of the kidneys, heart and brain of animals.

Patients with malignant hypertension, whose average age was 45.5 is no, upon receipt complained of headache (temporal, and occipital areas, pain in the left half of the chest, not disappearing after administration of nitroglycerin, tachycardia, increased blood pressure, fatigue, sometimes observed nosebleeds.

From the anamnesis it is known that for 10-14 days prior to the holding of intravenous prostaglandin E2 patients were on standard anti-hypertensive therapy and therapy diuretic drugs, which proved ineffective.

Patients underwent treatment with prostaglandin E2 in the form 0,0008% solution intravenously which was performed from a speed of 50-100 ng/kg/min Rate of infusion of the drug was increased every 10 min 20-40 ng/kg/min, leading up to 150-300 ng/kg/min, for 40 to 60 minutes Course of treatment was three prolonged injections with intervals of 1-2 days.

Registered HELL, investigated the state of adenylyl cyclase system lymphocytes in patients with essential hypertension, investigated the excretion of endogenous renal prostaglandins in patients with severe arterial hypertension, assessed the functional activity of platelets in these patients. The blood pressure was in the range of from 180/110 to 240/150 mm RT. Art.

Evaluation of the effectiveness of the treatment was carried out under the regulation of adenylyl cyclase system l is Mazitov hypertension in hypertensive patients with refractory arterial hypertension, diagnosing necorrigiruemy refractory arterial hypertension in patients with hypertension; 2) to assess the excretion of endogenous renal prostaglandins in patients with severe and refractory malignant hypertension; 3) to assess the impact of the rate of infusion prostenona (prostaglandin E2) on the functional activity of platelets in patients with severe or malignant hypertension.

1. Method for determining properties of β2-adrenoretseptorov adenylyl cyclase lymphocytes and studying the regulation of this system of cells under the influence of the rate of infusion of prostaglandin E2 applied to the examination of 16 men with normal blood pressure at age 32-46 years and 19 men with hypertension II B stage (classification Allasnetkova) aged 30-58 years, refractory to combination anti-hypertensive therapy. 10 days before the start of the study had abolished all drugs, except drug zinc. Treatment with prostaglandin E2 consisted of 3 intravenous infusions prostenona conducted with an interval of 1 day.

For research β2-adrenoreceptors adenylate cyclase complex lymphocytes venous blood was taken at 9 a.m. in the patient supine. Allocated menagerie lymphocytes. The density of the surface β2-adrenergic receptors was determined by the method of receptor binding in the suspension of intact cells using as ligand 125-1-cyanobenzyl; the affinity of the receptors for 1-isoproterenol was determined by the displacement of 125-1-cyanobenzyl 1-isoproterenol in the presence of 1 mm of sodium ascorbate; calculating the dissociation constant (KD) of the agonist. Adenylate cyclase activity of lymphocytes was determined in cell homogenates using as substrate α(32 p)-ATP. Stimulation of adenylate cyclase conducted 0.1 mm 1-isoproterenol; 0.1 mm Gpp(NH) p(guanyl-5-iminodiethanol); 0,03 mm Forskolin and concomitant exposure to 0.1 mm 1-isoproterenol and 0.1 mm Gpp (NH)p.

Density β2-adrenergic receptors and their affinity to 1-isoproterenol and the state of the adenylyl cyclase system were determined the day before the 1st infusion of prostaglandin E2 and after 1, 7 and 14 days after the 3rd infusion of prostaglandin E2.

Thus, the latter definition is the condition β2-adrenoretseptorov adenylyl cyclase system of the lymphocytes was carried out on the background of combined antihypertensive therapy; srad was defined as the sum of the diastolic blood pressure and 1/3 pulse HELL.

Hypertension in hypertensive patients with stable severe hypertension (BP amounted 202,9/123 mm RT. Art.) after three infusions PG E2 reduction of blood pressure after 1 day was 8.1±2.2 mm RT. century, after 7 days and 23.1±2.9 mm RT. Art., on the 14th day of 37.3±3.4 mm RT. Art.

2. Method of assessing violations excretion of endogenous renal prostaglandins applied to survey the AI 22 hypertensive patients with stable high arterial hypertension, of which 7 patients had arterial hypertension was refractory to combination anti-hypertensive therapy, and 7 patients with essential hypertension is a syndrome of malignant hypertension. All patients nitrogen-emission renal function was preserved. During the survey period patients dieted No. 10, daily fluid intake was 1.3 to 1.8 liters All patients took the drug tint. The control group consisted of 14 healthy individuals surveyed in the hospital.

Metabolism of renal prostaglandins PG E2 and prostaglandin PG F2á was assessed by daily excretion of these prostaglandins with urine, measured in nanograms per day. Urine was stored a t -20°C. the Content of prostaglandin E2 and prostaglandin F2á in the urine was determined by radioimmunoassay method.

3. Method of assessing the impact of the rate of infusion of prostaglandin E2 on the functional activity of platelets used in 12 patients with severe or malignant hypertension (8 patients was hypertension II B stage, 4 - malignant hypertension) and in 8 healthy persons Symptoms of malignant syndrome served as high blood pressure (above 220/130-140 mm RT. Art. and expressed changes of the fundus by type of neuromyopathy. All patients were refractory to a combined antihypertensive therapy; diastolic blood pressure Navone therapy remained at the level of 110-120 mm RT. Art. the Amount of aggregation was measured on a precision laser aggregometry. The study applied the method of Bourne.

All patients underwent infusion of prostaglandin E2 by the present method. Blood was taken for analysis in patients with shock from the cubital vein after 1 day after two infusions of the drug. Blood stabilized with 0.13 M solution of sodium citrate in the ratio of 1:9, the blood pH was brought to 7.4. The blood was centrifuged at 200g for 7 minutes. The supernatant using plastic pipettes were placed in separate test tubes and kept at room temperature. For the preparation of depleted platelet plasma have repeated centrifugation with acceleration 2000g for 30 minutes.

To determine the relative number of platelets in the suspension used a special microcentrifuge cuvette, to which was added 1 ml of the investigated suspension of blood platelets and 0.1 ml of 50 mm solution of EGTA. Platelets were besieged at 2000 g, and the largest platelet post estimated value of thrombocytosisa. In the study of the aggregation ability of the relative cell volume was brought up to 0.25% by dilution with autologous manner depleted platelet plasma. As inducer of aggregation solution was used ADP at a final concentration of 0,1-0,2-0,5-1 µm. The solution ADP desired concentrations were obtained by diluting the inductor in races is the thief Tirade pH +7,4. The degree of aggregation was measured when the amplitude changes of the optical signal by the action of ATP in percent of the maximum possible amplitude.

In patients when used as an inductor of low concentrations of ATP (0.1 ám) platelet aggregation was 7.8 times higher than in healthy (640±120 relative units and 83±26 PU, respectively). After infusion of PG E2 platelet aggregation decreased to 128±27 PU normalization of the sensitivity of platelets to ADP at low concentrations (0.1 ám). It is this concentration of ADP occurs in normal blood, which can be triggering early for the occurrence of microvascular thrombosis, especially in malignant hypertension.

Way of the following examples.

Example 1

Male rats breed SHR 9 months of age weighing 300 g with spontaneous hypertension were registered HELL in the tail artery bloodless method and noted the increase in blood pressure. Prior to the introduction of prostaglandin E2 blood pressure of the animal was to 173.3 mm RT. Art. received treatment with prostaglandin E2 in the form 0,0008% solution intravenously which was performed from a speed of 100 ng/kg/min, increasing the speed every 10 min to 40 ng/kg/min, leading up to 300 ng/kg/min for 60 min, and the rate was three p is olenguruone injections with intervals of 24 hours. Under the influence of the introduction of prostaglandin E2 decreased the HELL up 143,6 mm RT. senior Dynamic study depressor reflex after infusion of prostaglandin E2 showed that the reflex was increased from -6,0 before therapy to -19 mm after treatment with PG E2. There is an increase in the excretion of endogenous PG E2 kidneys from 4.6 to 4.9 ng/h in 2.5 weeks after the course of injections of prostaglandin E2 morphological study of the kidneys, Pia mater and the myocardium.

Morphologically, it was noted the plethora of glomerular and peritubular capillaries, the plethora juxtamedullary zone; in addition, it was expressed plethora microvascular infarction; plethora, and swelling of the soft meninges; the plethora intracerebrally vessels.

Example 2

Rat male breed SHR weight 290 g of 9-months of age with spontaneous hypertension were registered HELL in the tail artery of rats bloodless method. Received treatment with prostaglandin E2 in the form 0,0008% solution intravenously which was performed from a speed of 50 ng/kg/min, increasing the speed every 10 min at 20 ng/kg/min, bringing to 150 ng/kg/min for 60 min, and the rate was three prolonged injections with intervals between them 2 days. Prior to the introduction of prostaglandin E2 blood pressure in sideimage animal was of 163.7 mm RT. century, under the influence of the introduction of prostaglandin E2 decreased the HELL up 138,4 mm Art. RT Dynamic study depressor reflex after infusion of prostaglandin E2 showed that the reflex was increased from - 7.0 to - 18 mm increased excretion of endogenous PG E2 kidneys from 4.5 to 4.9 ng/h

After 2.5 weeks after the course of injections of prostaglandin E2 morphological study of the kidneys, Pia mater and myocardium. Morphologically there was a marked increase in glomerular blood and peritubular capillaries, increasing blood with stasis of blood in juxtamedullary area; expressed plethora microvascular infarction, increased blood intracerebrally vessels and swelling of the soft meninges.

Example 3

The rat 9 months old breed SHR weight 280 g with spontaneous hypertension were registered HELL in the tail artery bloodless method. Received treatment with prostaglandin E2 in the form 0,0008% solution intravenously which was performed from a speed of 70 ng/kg/min, increasing the speed every 10 min at 30 ng/kg/min, leading up to 160 ng/kg/min for 40 min, and the rate was three prolonged injections with intervals between them 36 hours. Prior to the introduction of prostaglandin E2 blood pressure in the studied rats were 167mm RT. century; under the influence of the introduction of prostaglandin E2 decreased the blood pressure to 140 mm RT. senior Dynamic study depressor reflex after infusion of prostaglandin E2 showed that the reflex was increased from - 6.0 to - 18 mm increased excretion of endogenous PG E2 kidneys from 4.6 to 4.9 ng/h

After 2.5 weeks after the course of injections of prostaglandin E2 morphological study of the kidneys, Pia mater and myocardium. Morphologically there was a marked increase in glomerular blood and peritubular capillaries and juxtamedullary zone; in addition, it was noted pronounced stasis and dilation of the microvasculature of the myocardium; swelling of the soft meninges was accompanied by strong volume intracerebrally vessels.

Infusion of exogenous prostaglandin E2 resulted in a high, persistent for several months, the decrease in systemic blood pressure, a significant strengthening of the depressor reflex and increase excretion of endogenous renal prostaglandin E2, as well as pronounced vasodilation of blood vessels of the kidneys, heart and brain of animals.

Example 4

Patient M., 43 years old, with malignant hypertension, when she was complaining of a headache in the temporal and occipital regions, tachycardia, increased blood pressure, b is the stream of fatigue.

From the anamnesis it is known that 14 days before the holding of intravenous prostaglandin E2 were on standard anti-hypertensive therapy and therapy diuretic drugs, which proved ineffective.

The patient received treatment with prostaglandin E2 in the form 0,0008% solution intravenously which was performed from a speed of 100 ng/kg/min Rate of infusion of the drug was increased every 10 min to 40 ng/kg/min, leading up to 300 ng/kg/min for 60 min Course of treatment consisted of three prolonged injections with intervals between them 1 day.

Registered HELL, investigated the state of adenylyl cyclase system lymphocytes in patients with essential hypertension, investigated the excretion of endogenous renal prostaglandins in patients with severe arterial hypertension, assessed the functional activity of platelets in these patients. The AD was 240/150 mm RT. Art.

Evaluation of the effectiveness of the treatment was carried out under the regulation of adenylyl cyclase system lymphocytes in hypertensive patients with refractory arterial hypertension diagnosing necorrigiruemy refractory arterial hypertension in patients with hypertension; 2) to assess the excretion of endogenous renal prostaglandins in patients with severe refractory and zlocesto the Noah arterial hypertension; 3) to assess the impact of the rate of infusion prostenona (prostaglandin E2) on the functional activity of platelets in patients with severe or malignant hypertension.

1. Method for determining properties of β2-adrenoretseptorov adenylyl cyclase lymphocytes and studying the regulation of this system of cells under the influence of the rate of infusion of prostaglandin E2 applied in a particular patient. 10 days before the start of the study had abolished all drugs, except drug zinc. Treatment with prostaglandin E2 consisted of 3 intravenous infusions prostenona conducted with an interval of 1 day.

For research β2-adrenoreceptors adenylate cyclase complex lymphocytes venous blood was taken at 9 a.m. in the patient supine. Allocated menagerie lymphocytes. The density of the surface β2-adrenergic receptors was determined by the method of receptor binding in the suspension of intact cells using as ligand 125-1-cyanobenzyl; the affinity of the receptors for 1-isoproterenol was determined by the displacement of 125-1-cyanobenzyl 1-isoproterenol in the presence of 1 mm of sodium ascorbate; calculating the dissociation constant (KD) of the agonist. Adenylate cyclase activity of lymphocytes was determined in cell homogenates using as substrate α(32 p)-ATP. Stimulation of adenylate cyclase p is bodily 0.1 mm 1-isoproterenol; 0.1 mm Gpp(NH) p(guanyl-5-iminodiethanol); 0,03 mm Forskolin and concomitant exposure to 0.1 mm 1-isoproterenol and 0.1 mm Gpp (NH)p.

Density β2-adrenergic receptors and their affinity to 1-isoproterenol and the state of the adenylyl cyclase system were determined the day before the 1st infusion of prostaglandin E2 and after 1, 7 and 14 days after the 3rd infusion of prostaglandin E2. In the patient source increased density β2-adrenoreceptor 65% and an affinity for catecholamines decreased 3.9 times compared with healthy people. All this indicates the data demonstrate that differently modulated β2-adrenergic receptors. After infusion of prostaglandin PG E2 density β2-adrenergic receptors decreases by 1.7 times in 7 days and affinity β2-adrenergic receptors to catecholamines is increased 10 times. Affinity β2-adrenergic receptors to catecholamines in 14 days increased 28 times. Then there is resensitization β2-adrenergic receptors.

Thus, the latter definition is the condition β2-adrenoretseptorov adenylyl cyclase system of the lymphocytes was carried out on the background of combined antihypertensive therapy; srad was defined as the sum of the diastolic blood pressure and 1/3 pulse HELL.

This patient's hypertension with stable severe arterial hypertension after three infusions PG E2 reduction of blood pressure after 1 day amounted to 5.9 m the RT. century, after 7 days of 20.1 mm RT. Art., on the 14th day 33,9 mm Art. RT

2. Method of assessing violations excretion of endogenous renal prostaglandins applied in a particular patient. Before treatment the nitrogen-emission kidney function is preserved. During the examination the patient dieted No. 10, daily fluid intake was on average 1.5 L. the Patient received the drug tint.

The renal metabolism of prostaglandin E2 and prostaglandin F2á was assessed by daily excretion of these prostaglandins with urine, measured in nanograms per day. Urine was stored at t-20°C. the Content of prostaglandin E2 and prostaglandin F2á in the urine was determined by radioimmunoassay method.

3. We have estimated the influence of the rate of infusion of prostaglandin E2 on the functional activity of platelets in the patient. The amount of aggregation was measured on a precision laser aggregometry. The study applied the method of Bourne.

All patients underwent infusion of prostaglandin E2 by the present method. Blood was taken for analysis in patients with shock from the cubital vein after 1 day after two infusions of the drug. Blood stabilized with 0.13 M solution of sodium citrate in the ratio of 1:9, the blood pH was brought to 7.4. The blood was centrifuged at 200g for 7 minutes. The supernatant using plastic pipettes were placed in separate test tubes and kept at room temperature. For made the Oia depleted platelet plasma have repeated centrifugation with acceleration 2000g for 30 minutes.

To determine the relative number of platelets in the suspension used a special microcentrifuge cuvette, to which was added 1 ml of the investigated suspension of blood platelets and 0.1 ml of 50 mm solution of EGTA. Platelets were besieged at 2000 g and the largest platelet post estimated value of thrombocytosisa. In the study of the aggregation ability of the relative cell volume was brought up to 0.25% by dilution with autologous manner depleted platelet plasma. As inducer of aggregation solution was used ADP in breeding 0,1 -0,2 -0,5 -1 μm. The solution ADP desired concentrations were obtained by diluting the inductor in the solution of Tyrode pH+ 7,4. The degree of aggregation was measured when the amplitude changes of the optical signal by the action of ATP in percent of the maximum possible amplitude.

The patient when used as an inductor of low concentrations of ATP (0.1 ám) platelet aggregation was 760 relative units. After infusion of PG E2 platelet aggregation decreased to 155 PU normalization of the sensitivity of platelets to ADP at low concentrations (0.1 ám).

Example 5

Patient 3., 47 years with arterial hypertension at admission complains of headache, pain in the left half of the chest, not disappearing after administration of nitroglycerin, increase arterioles the pressure.

From the anamnesis it is known that 10 days before the holding of intravenous prostaglandin E2 she was on standard anti-hypertensive therapy and therapy diuretic drugs, which proved ineffective.

The patient was treated with prostaglandin E2 in the form 0,0008% solution intravenously which was performed from a speed of 50 ng/kg/min Rate of infusion of the drug was increased every 10 min at 20 ng/kg/min, bringing to 150 ng/kg/min for 60 min Course of treatment consisted of three prolonged injections with intervals between them 2 days.

Registered HELL, investigated the state of adenylyl cyclase system lymphocytes in patients with essential hypertension, investigated the excretion of endogenous renal prostaglandins in patients with severe arterial hypertension, assessed the functional activity of platelets in these patients. The blood pressure was 180/110 mm Art. RT

Evaluation of the effectiveness of the treatment was carried out under the regulation of adenylyl cyclase system lymphocytes in hypertensive patients with refractory arterial hypertension diagnosing necorrigiruemy refractory arterial hypertension in patients with hypertension; 2) to assess the excretion of endogenous renal prostaglandins in patients with severe refractory and slocate the state arterial hypertension; 3) to assess the impact of the rate of infusion prostenona (prostaglandin E2) on the functional activity of platelets in patients with severe or malignant hypertension.

1. Method for determining properties of β2-adrenoretseptorov adenylyl cyclase lymphocytes and studying the regulation of this system of cells under the influence of the rate of infusion of prostaglandin E2 examined this patient, and for 10 days prior research has canceled all drugs, except drug zinc. Treatment with prostaglandin E2 consisted of 3 intravenous infusions prostenona conducted with an interval of 2 days.

For research β2-adrenoreceptors adenylate cyclase complex lymphocytes venous blood was taken at 9 a.m. in the patient supine. Allocated menagerie lymphocytes. The density of the surface β2-adrenergic receptors was determined by the method of receptor binding in the suspension of intact cells using as ligand 125-1-cyanobenzyl; the affinity of the receptors for 1-isoproterenol was determined by the displacement of 125-1-cyanobenzyl 1-isoproterenol in the presence of 1 mm of sodium ascorbate; calculating the dissociation constant (KD) of the agonist. Adenylate cyclase activity of lymphocytes was determined in cell homogenates using as substrate α(32 p)-ATP. Stimulation adenylate is clazy conducted 0.1 mm 1-isoproterenol; 0.1 mm Gpp(NH) p(guanyl-5-iminodiethanol); 0,03 mm Forskolin and concomitant exposure to 0.1 mm 1-isoproterenol and 0.1 mm Gpp (NH)p.

Density β2-adrenergic receptors and their affinity to 1-isoproterenol and the state of the adenylyl cyclase system were determined the day before the 1st infusion of prostaglandin E2 and after 1, 7 and 14 days after the 3rd infusion of prostaglandin E2. The latter definition is the condition β2-adrenoretseptorov adenylyl cyclase system of the lymphocytes was carried out on the background of combined antihypertensive therapy; srad was defined as the sum of the diastolic blood pressure and 1/3 pulse HELL.

After three infusions PG E2 reduction of blood pressure after 1 day amounted to 10.3 mm RT. century, after 7 days - 26 mm RT. Art., on the 14th day of 40.7 mm RT. Art.

2. Assessed violations excretion of endogenous renal prostaglandins have a patient with essential hypertension with stable high hypertension while maintaining the nitrogen-emission of kidney function. During the examination the patient dieted No. 10, daily fluid intake was 1.8 liters of Standard therapy - drug zinc.

The renal metabolism of prostaglandin E2 and prostaglandin F2á was assessed by daily excretion of these prostaglandins with urine, measured in nanograms per day. Urine was stored at t-20°C. the Content of prostaglandin E2 and prostaglandin F2á in the urine was determined radioimmunological the m method.

Daily excretion of prostaglandins E2 before and after treatment amounted to 211 ng/day and 234 ng/day, respectively.

3. We have estimated the influence of the rate of infusion of prostaglandin E2 on the functional activity of platelets, applied at the patient H. the Amount of aggregation was measured on a precision laser aggregometry. The study applied the method of Bourne.

Conducted infusion of prostaglandin E2 by the present method. Blood was taken for analysis of fasting from the cubital vein after 1 day after two infusions of the drug. Blood stabilized with 0.13 M solution of sodium citrate in the ratio of 1:9, the blood pH was brought to 7.4. The blood was centrifuged at 200g for 7 minutes. The supernatant using plastic pipettes were placed in separate test tubes and kept at room temperature. For the preparation of depleted platelet plasma have repeated centrifugation with acceleration 2000g for 30 minutes.

To determine the relative number of platelets in the suspension used a special microcentrifuge cuvette, to which was added 1 ml of the investigated suspension of blood platelets and 0.1 ml of 50 mm solution of EGTA. Platelets were besieged at 2000 g, and the largest platelet post estimated value of thrombocytosisa. In the study of the aggregation ability of the relative cell volume was brought up to 0.25% by dilution with autologous way about DNEVNOY platelet plasma. As inducer of aggregation solution was used ADP at a final concentration of 0.1; -0,2; -0,5; -1 μm. The solution ADP desired concentrations were obtained by diluting the inductor in the solution of Tyrode pH +7,4. The degree of aggregation was measured when the amplitude changes of the optical signal by the action of ATP in percent of the maximum possible amplitude.

When used as an inductor of low concentrations of ATP (0.1 ám) aggregation of platelets, the patient was 520 relative units. After infusion of PG E2 platelet aggregation decreased to 101 PU normalization of the sensitivity of platelets to ADP at low concentrations (0.1 ám).

Example 6

Patient K., aged 44, with malignant hypertension at admission complains of pain in the heart, headache, tachycardia, increased blood pressure, sometimes accompanied by nosebleeds.

From the anamnesis it is known that during the 12 days prior to the holding of intravenous prostaglandin E2 patient was on standard anti-hypertensive therapy and therapy diuretic drugs, which proved ineffective.

The patient received treatment with prostaglandin E2 in the form 0,0008% solution intravenously which was performed from a speed of 80 ng/kg/min Rate of infusion of the drug was increased every 10 min at 30 ng/kg/which in leading up to 170 ng/kg/min for 40 min Course of treatment consisted of three prolonged injections with intervals between them 36 hours

Registered HELL, investigated the state of adenylyl cyclase lymphocytes, investigated the excretion of endogenous renal prostaglandins have evaluated the functional activity of platelets. The AD was 220/140 mm RT. Art.

1. Defined properties β2-adrenoretseptorov adenylyl cyclase lymphocytes and studied the state of this system of cells under the influence of the rate of infusion of prostaglandin E2. 12 days before the start of the study had abolished all drugs, except drug zinc. Treatment with prostaglandin E2 consisted of 3 intravenous infusions prostenona conducted with an interval of 36 hours

For research β2-adrenoreceptors adenylate cyclase complex lymphocytes venous blood was taken at 9 am in the position of the patient lying down. Allocated menagerie lymphocytes. The density of the surface β2-adrenergic receptors was determined by the method of receptor binding in the suspension of intact cells using as ligand 125-1-cyanobenzyl; the affinity of the receptors for 1-isoproterenol was determined by the displacement of 125-1-cyanobenzyl 1 isoproterenol in the presence of 1 mm of sodium ascorbate; calculating the dissociation constant (KD) of the agonist. The activity of Aden is lattices lymphocytes was determined in cell homogenates using as substrate α(32 p)-ATP. Stimulation of adenylate cyclase conducted 0.1 mm 1-isoproterenol; 0.1 mm Gpp(NH) p(guanyl-5-iminodiethanol); 0,03 mm Forskolin and concomitant exposure to 0.1 mm 1-isoproterenol and 0.1 mm Gpp (NH)p.

Density β2-adrenergic receptors and their affinity to 1-isoproterenol and the state of the adenylyl cyclase system were determined the day before the 1st infusion of prostaglandin E2 and after 1, 7 and 14 days after the 3rd infusion of prostaglandin E2.

In a patient after three infusions PG E2 reduction of blood pressure after 1 day was 8.3 mm RT. century, after 7 days - 22,9 mm RT. Art., on the 14th day - 37,4 mm RT. Art.

2. Assessed violations excretion of endogenous renal prostaglandins while maintaining the nitrogen-emission of kidney function. During the examination the patient dieted No. 10, daily fluid intake was 1.5 L. the Patient took the drug tint.

The renal metabolism of prostaglandin E2 and prostaglandin F2á was assessed by daily excretion of these prostaglandins with urine, measured in nanograms per day. The content of prostaglandin E2 and prostaglandin F2á in the urine was determined by radioimmunoassay method.

Daily excretion of renal prostaglandins urine was before and after treatment 215 ng/day or 236 ng/day, respectively.

3. Conducted an impact assessment of the rate of infusion of prostaglandin E2 on the functional activity of platelets of the patient. The value of agregate is measured on a precision laser aggregometry. The study used the method of Bourne. Blood was taken for analysis in patients with shock from the cubital vein after 1 day after two infusions of the drug. Blood stabilized with 0.13 M solution of sodium citrate in the ratio of 1:9, the blood pH was brought to 7.4. The blood was centrifuged at 200g for 7 minutes. The supernatant using plastic pipettes were placed in separate test tubes and kept at room temperature. For the preparation of depleted platelet plasma have repeated centrifugation with acceleration 2000g for 30 minutes.

To determine the relative number of platelets in the suspension used a special microcentrifuge cuvette, to which was added 1 ml of the investigated suspension of blood platelets and 0.1 ml of 50 mm solution of EGTA. Platelets were besieged at 2000 g and the largest platelet post estimated value of thrombocytosisa. In the study of the aggregation ability of the relative cell volume was brought up to 0.25% by dilution with autologous manner depleted platelet plasma. As inducer of aggregation solution was used ADP at a final concentration of 0.1; -0,2; -0,5; -1 μm. The solution ADP desired concentrations were obtained by diluting the inductor in the solution of Tyrode pH +7,4. The degree of aggregation was measured when the amplitude changes of the optical signal by the action of ATP in percent from the biggest prob is the author of the amplitude.

The amount of platelet aggregation in a patient was 740 relative units. After infusion of PG E2 platelet aggregation decreased to 142 per unit normalization of the sensitivity of platelets to ADP at low concentrations (0.1 ám).

Tested the proposed method on 63 patients. Tests confirmed that the purpose of this invention is to improve the efficiency of treatment of arterial hypertension.

A method of treating hypertension by administration of drugs, characterized in that the additional use of prostaglandin E2 in the form 0,0008% solution intravenously which shall, from a speed of 50-100 ng/kg/min, increasing the speed every 10 min 20-40 ng/kg/min, leading up to 150-300 ng/kg/min, for 40-60 min, and the rate was three prolonged injections with intervals of 1-2 days.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I): where: A is a monocyclic or polycyclic aryl or heteroaryl group, where the heteroaryl radical denotes a 5-10-member cyclic system containing at least one heteroaromatic ring and containing at least one heteroatom selected from O, S and N; optionally substituted with one or more substitutes independently selected from a group comprising halogen atoms, C1-4alkyl, C3-8cycloalkyl, C3-8cycloalkyl-C1-4alkyl, C1-4alkoxy and a hydroxyl group; B is a monocyclic nitrogen-containing heteroaryl group, where the heteroaryl radical denotes a 5-6-member heteroaromatic ring containing at least one heteroatom selected from S and N; optionally substituted with one or more substitutes selected from a group consisting of halogen atoms, C1-4alkyl, C3-8cycloalkyl, C3-8cycloalkyl-C1-4alkyl, aryl and C1-8alkylthio; either a) R1 is a group of formula: -L-(CR'R")n-G, where L is a binding group selected from a group consisting of a direct bond, -(CO)-, -(CO)NR'- and -SO2-; R' and R" is independently selected from hydrogen atoms; n assumes values from 0 to 1; and G is selected from a group consisting of a hydrogen atom and C1-4alkyl, aryl, heteroaryl, where the heteroaryl radical denotes a 5-6-member heteroaromatic ring containing at least one heteroatom selected from O, S and N; C3-8cycloalkyl and saturated heterocyclic groups, where heterocyclic group denotes a non-aromatic saturated 6-member carbocyclic ring in which one or two carbon atoms are substituted with a N heteroatom; where alkyl, C3-8cycloalkyl, aryl or heteroaryl groups are unsubstituted or substituted with one or more substitutes selected from halogen atoms; and R2 is a group selected from hydrogen atoms, halogen atoms and C1-4alkyl, C2-5alkynyl, C1-4alkoxy, -NH2 and cyano groups, where alkyl and alkynyl groups may be unsubstituted or substituted with one aryl group; or b) R2, R1 and -NH- group to which R1 is bonded form a group selected from groups of formulae and , where: Ra is selected from a hydrogen atom or groups selected from C1-4alkyl, C3-8cycloalkyl, aryl, aryl-C1-4alkyl, heteroaryl, where the heteroaryl radical denotes a 5-6-member heteroaromatic ring containing at least one heteroatom selected from O and N; saturated heterocyclic rings, where the heterocyclic group denotes a non-aromatic saturated 6-member carbocyclic ring in which one carbon atom is substituted with a heteroatom selected from O and N; and C1-4alkylthio; where the aryl or heteroaryl groups are unsubstituted or substituted with one or more groups selected from halogen atoms, cyano group, trifluoromethoxy and carbamoyl; Rb denotes hydrogen; and pharmaceutically acceptable salts thereof and N-oxides; provided that the compound is not selected from N-[6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-ylpyrazin-2-yl]benzamide, N-[3-ethoxycarbonyl-6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-ylpyrazin-2-yl]benzamide, and N-[3-ethoxycarbonyl-6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-ylpyrazin-2-yl]formamide. The invention also relates to a pharmaceutical composition, use of compounds in any of claims 1-20, a method of treating a subject, as well as a composite product.

EFFECT: obtaining novel biologically active compounds having adenosine A2B receptor antagonist activity.

27 cl, 160 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) or pharmaceutically acceptable salts thereof where R1 and R2 together denote a group selected form groups of formula (III-1): , where R9 denotes 1) a lower alkyl group, optionally substituted with a halogen atom or lower alkoxy group, 2) an aryl group, 3) an aralkyl group, 4) a heteroarylalkyl group, 5) a heteroaryl group, where the aryl, aralkyl, heteroarylalkyl and heteroaryl groups can be substituted with a halogen atom, lower alkyl group, optionally substituted with a lower alkoxy group or 1-3 halogen atoms, lower alkoxy group, optionally substituted with 1-3 halogen atoms, cyano group, hydroxy group, alkylsulphonyl group, cycloalkylsulphonyl group, aryl group, heteroaryl group, alkylaminocarbonyl group, alkanoyl amino group, alkyl amino group or dialkylamino group; R10 denotes a lower alkyl group, optionally substituted with 1-3 halogen atoms, or a lower alkylsulphonyl group; X9-X12 denotes a carbon atom or a nitrogen atom, where the carbon atom can be independently substituted with a lower alkyl group, optionally substituted with a halogen atom or a lower alkoxy group, lower alkoxy group, optionally substituted with a halogen atom, or a cyano group or a halogen atom; R3 denotes a) a group of formula (II-1): (ii-U where R4 and R5, taken together with a nitrogen atom, form a 5- or 6-member monocyclic ring, where the monocyclic ring may contain a substitute in form of a lower alkyl group, m1 equals 3; or b) a group of formula (II-2): , where R6 denotes a lower alkyl group or cycloalkyl group; m2 equals 1 or 2; X1-X4 all denote carbon atoms, or one of X1-X4 denotes a nitrogen atom and the rest denote carbon atoms; and where "heteroaryl" in each case relates to a 5- or 6-member aromatic ring containing 1-3 heteroatoms selected from a nitrogen atom, oxygen atom and a sulphur atom. The invention also relates to a histamine H3 receptor antagonist or inverse agonist, as well as a preventive or medicinal agent.

EFFECT: obtaining novel biologically active compounds, having histamine H3 receptor antagonist or inverse agonist activity.

11 cl, 8 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: compounds are suitable for use as kinase 1β-adrenergic receptor (βARK-1) inhibitors. The invention also relates to compositions containing such compounds and to use of compounds of formula to treat and prevent chronic heart failure, hypertension myocardial ischemia and hepatitis C viral infections (HCV) and for preventing opiate addiction. The invention also pertains to methods of producing formula (I) compounds.

EFFECT: more effective use of the compounds.

11 cl, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described 3,4-substituted piperidines applicable in diagnostics and drug therapy of a warm-blooded animal, preferentially for therapy of a disease which depends on renin activity; application of a compound of such kind for preparing a pharmaceutical composition for therapy of the disease which depends on renin activity; application of the compound of such kind for therapy of the disease which depends on renin activity; the pharmaceutical compositions containing 3,4-substituted piperidine, and/or a therapeutic mode involving administration of 3,4-substituted piperidine, a method for producing 3,4-substituted piperidine. The preferential compound (which also can be presented in the form of salts) are described by formula I' wherein R1, R2, T, R3 and R4 are such as described by the patent claim.

EFFECT: production of the compounds for therapy of the disease which depends on renin activity.

28 cl, 1 tbl, 375 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: agent for treating systemic hypertension contains as an active ingredient a compound presented by formula (1): or its pharmaceutically acceptable salt.

EFFECT: preparation of the new agent for treating systemic hypertension.

12 cl, 7 ex, 7 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (I) , where the dotted line is either absent or denotes a double bond; R1 denotes H or C1-6-alkyl, possibly substituted with a CN group, or denotes a phenyl or sulphonyl phenyl, substituted with one or more B groups, or denotes -(CH2)m-Ra, where Ra denotes: NRiRii, C3-6-cycloalkyl, 6-member heterocycloalkyl, which denotes a univalent saturated group which contains one nitrogen heteroatom, the rest are carbon atoms, aryl, which can be substituted with one or more B groups, or denotes -(CH2)n-(CO)-Rb or -(CH2)n-(SO2)-Rb, where Rb denotes: NRiRii, 5-6-member heterocycloalkyl, which denotes a univalent saturated group containing one or more heteroatoms selected from nitrogen, oxygen, the rest are carbon atoms, aryl or 5- or 6-member heteroaryl, which denotes an aromatic ring containing two heteroatoms as ring members, the said heteroatoms selected from N or O, the rest are carbon atoms; which can possibly be substituted with one or more B groups, R2 denotes one or more H, halo, C1-6-alkyl, C1-6-alkoxy, R3 denotes H or-(CO)-Rc, where Rc denotes: C1-6-alkyl, 5-member heterocycloalkyl, which denotes a univalent saturated group containing one nitrogen heteroatom, the rest are carbon atoms possibly substituted with C1-6-alkyl, or denotes C1-6-alkyl; R4 denotes H; R5 denotes H, C1-6-alkyl, -(CH2)m-NRiRii, -(CH2)n-(CO)-Rb, where Rb denotes NRiRii or a 6-member heterocycloalkyl which denotes a univalent saturated group which contains one nitrogen heteroatom, the rest are carbon atoms, when the dotted line is absent or is absent when the dotted line denotes a double bond; R6 is absent, when the dotted line denotes a double bond; R7 denotes Cl or NReRf, where Re and Rf denotes H or C1-6-alkyl, or Re and Rf together with the nitrogen atom to which they are bonded form a 6-member heterocycloalkyl which denotes a univalent saturated group containing one or two heteroatoms selected from nitrogen, oxygen, the rest are carbon atoms; which can be substituted with C1-6-alkyl, or R6 and R7 together form a C=O group, when the dotted line is absent; B denotes halogen, C1-6-alkoxy, (CRiiiRiv)n-phenyl; Ri and Rii denote H, C1-6-alkyl -C(O)-C1-6-alkyl; Riii and Riv denote C1-6-alkyl; m equals to 1 or 2, n equals 0 or 1; as well as to pharmaceutically acceptable salts thereof. The invention also relates to a pharmaceutical composition, as well as to use of compounds of formula (I), (I-a) or (1-b).

EFFECT: obtaining novel biologically active compounds having activity on V1a receptor.

12 cl, 48 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine and concerns methods of treating diseases with using VEGF antagonists. Substance of the invention involves application of a VEGF antagonist containing VEGFR1R2-FcΔ C1 (a) SEQ ID NO:4 in preparing a drug for hypertension reduction, in treating the diseases associated with administering the VEGF antagonist where the treatment is conducted by subcutaneous introduction.

EFFECT: advantage of the invention consists in reducing side effects associated with treating the diseases by administering the VEGF antagonist.

8 cl, 3 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, namely to an agent exhibiting antihypertensive activity which represents 1-alkyl-2-alkylcarbamoylglycerins of general formula I . In formula I R means hydrocarbon radical -(CH2)nCH3 (n=10-18), R1 means methyl or ethyl. Also, the invention refers to a method for preparing the compounds of formula I. The method consists in the fact that parent 1-alkylglycerins of general formula II react with trimethylchlorosilane with using triethylamine in toluene medium at temperature -20°C to 0°C, then the reaction mass is added with appropriate alkylisocyanate and processed with ammonium bifluoride in methanol medium at room temperature.

EFFECT: preparation of the agent exhibiting antihypertensive activity.

2 cl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of organic chemistry and pharmaceutics and deals with novel anti-hypertension salt of general formula [(R1-COO-)·(H3N-R2)], where R1 is inhibitor of angiotensin-converting enzyme, selected from group, which consists of perindoprilat, ramiprilat, spiraprilat, benazeprilat, moexiprilat, trandalaprilat, fosinoprilat, enalaprilat, zofenoprilat or lisinopril, and R2 -calcium channel blocker, selected from group, consisting of amlodipine, lacidipine, felodipine, isradipine.

EFFECT: invention ensures reduction of therapeutic doses and side effects.

3 dwg, 2 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to amide of δ-amino-γ-hydroxy-ω-arylalcane acid of formula and its pharmaceutically acceptable salts. Also described are pharmaceutical compositions, which include said compounds, and application of said compounds for preparation of medication, intended for treatment of pathological states, associated with renin activity, in particular for treatment of hypertension.

EFFECT: obtaining pharmaceutically acceptable salts, which possess rennin-inhibiting ability.

21 cl, 161 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical industry, in particular to protective medication for retina neurons. Protective medication for retina neurons includes fluorine-containing derivatives of prostaglandin F2α as active component. Method of retina neurons protection. Method of prevention and treatment of eye disease, associated with injury of retina neurons.

EFFECT: medicine efficiently protects retina neurons.

10 cl, 1 dwg

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to obstetrics, and concerns a method of birth complications prevention in women with contracted pelvis. For this purpose, 3-4 days prior to an estimated delivery date, oestradiol dipropionate 1.0 ml is introduced intramuscularly, while 10% calcium gluconate 10.0 ml and 5% ascorbic acid 4.0 ml are introduced intravenously. Prepidil gel is introduced in the cervical canal.

EFFECT: invention provides facilitated advancement of a foetus head through the generative passages and, as consequence, reduced duration of delivery, decreased caesarian section and forceps operation cases, lower perinatal mortality and birth trauma rate.

2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to chemical and pharmaceutical industry and specifically to an agent which is ethyl ether (±)-11,15-dideoxy-16-methyl-16-hydroxyprostaglandin E1 of formula (I), which exhibits uterotonic activity. This compound relates to the family of 11-deoxyprostaglandines and has a chemical structure similar to misoprostol.

EFFECT: agent, which is more chemically stable and is twice less toxic, surpasses misoprostol on uterotonic activity which, along with synthetic availability and absence of side effects, makes it exceptionally promising in practical use for replacing misoprostol in gynaecological binary preparations.

2 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to gastroenterology, and concerns treating gastrointestinal disorders. That is ensured by administration of the effective amount of a halogenated prostaglandin compound and/or its tautomer.

EFFECT: method provides effective treatment in patients of any age and sex without involving electrolyte balance even in long-term introduction for 1 to 6 months and more.

54 cl, 8 tbl, 14 dwg, 6 ex

FIELD: chemistry.

SUBSTANCE: invention belongs to polymeric container for storage of prostaglandin F2α derivate aqueous preparation. Derivate has at least one fluor atom in its molecule. Polymeric container is made of propylene/ethylene copolymer in which propylene/ethylene ratio varies from 94.0/6.0 to 99.5/0.5. This container provides long time storage of prostaglandin F2α derivate liquid aqueous solution.

EFFECT: long time storable in aforementioned polymeric container product is offered.

5 cl, 1 dwg, 1 ex

FIELD: medicine.

SUBSTANCE: in early after-burn period, with underlying antiinflammatory, antibacterial and trophic treatment, additionally alprostadil in single dosing 40 mcg dissolved in 200 mg of physiologic saline is introduced intravenously drop-by-drop within 2 hours.

EFFECT: method allows for conventional and effective treatment of burns of the conjunctiva ensured by effect of alprostadil on pathogenic links of the burn disease.

3 ex

FIELD: medicine.

SUBSTANCE: therapy of the patients suffering from chronic lower limb ischemia involves sampling the autogenic blood cell mass in amount 6-8% of total blood volume by discrete plasmapheresis. Then the autogenic cell mass is incubated with pentoxifylline 10 ml during 20 min at room temperature with ATP 2 ml added. The prepared mass is reinfused to the patient. Thereafter, Vasaprostan is introduced in a dose 40 mkg/day with physiologic saline 200 ml as intravenous infusion during 3 hours. Therapeutic course is 10-15 daily procedures.

EFFECT: higher clinical effectiveness with regard to the pathology due to correction of hemodynamic disorders in an ischemic focus and improvement of rheological properties blood in the absence of absolute indications to surgical procedure or inability thereof.

2 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely surgery, and can be used for treatment of chronic arterial lower limb ischemia. It is ensured by mixing preparation Vasaprostan 20 mkg and human albumin 10% 100 ml. The mixture is incubated in a thermostat within 20 min at temperature 37°C and then slowly introduced to a patient intravenously drop-by-drop within 2-3 hours, once a day. Therapeutic course is 10 days.

EFFECT: incubation of Vasaprostan and albumin in a developed mode provides binding with protein and prolongation of therapeutic effect that in turn allows improving clinical effectiveness with decreasing therapeutic dose of the preparation.

1 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention concerns medicine, therapy. The way includes blood sampling and its centrifugation. Then allocation of erythrocyte fraction and plasma removal is carried out. An angiotropic medicinal substance in quantity of an average therapeutic dose on each 200 ml of erythrocyte fraction is administered into the allocated fraction. Then irradiation with low-intensity helium-neon laser radiation with 1.2 mW power within 20 minutes is performed. 100 ml of a normal saline solution on each 200 ml is added in erythrocyte fraction and returned within 1.5-2 hours. The way increases efficiency of treatment at the expense of including activisation of an angiotropic preparation in erythrocyte cells at a laser irradiation of packed red cells.

EFFECT: increase of treatment efficiency at the expense of including activisation of an angiotropic preparation in erythrocyte cells at a laser irradiation of packed red cells.

2 cl

FIELD: medicine.

SUBSTANCE: invention relates to medicine, particularly to ophthalmology. Invented is a composition for reducing intraocular pressure, treating glaucoma or ocular hypertension, containing from 0.005 to 0.02 wt %/ bimatoprost mass and from 100 mln-1 to 250 mln-1 benzalkonium chloride, where the said composition is a water based liquid, with content suitable for application into eyes. Invented also is a method which is useful in treating glaucoma or related ocular hypertension.

EFFECT: reduction of active component in the composition while retaining effectiveness of the composition and design of a method of its application for reduction of intraocular pressure when treating glaucoma or ocular hypertension.

17 cl, 5 ex, 2 dwg

FIELD: veterinary science.

SUBSTANCE: a sow should be twice injected with oxytocin and, additionally, intramuscularly about 2-4 h after afterbirth detachment one should introduce clathroprostin at the dosage of 1 ml. The innovation suggested is very efficient in preventing metritis-mastitis-agalactia and endometritis in sows, as well.

EFFECT: higher efficiency of prophylaxis.

1 ex, 1 tbl

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