UA146877U - PHARMACEUTICAL COMPOSITION - Google Patents

Abstract

The pharmaceutical composition in oral solid dosage form contains rosuvastatin or a pharmaceutically acceptable salt thereof and at least one excipient. Additionally, the composition comprises a chemical compound of structural formula (I), (I) a chemical compound of structural formula (II) or a prodrug form thereof, (II) a chemical compound of structural formula (III) or a pharmaceutically acceptable salt thereof, (III) a chemical compound of structural formula IV) (IV) and magnesium hydroxide.

Description

not M MN c) o

NT

8) (6;

C From sleep and "() a chemical compound of the structural formula (IM) (c) 9, in our sum

Se and magnesium hydroxide.

The useful model belongs to the field of medicine, in particular to pharmaceutical compositions for the simultaneous prevention and treatment of essential hypertension and hypercholesterolemia, accompanied by the prevention of cardiovascular disorders.

According to WHO, cardiovascular diseases are the leading cause of death worldwide.

Cardiovascular diseases (CC3) - a group of diseases of the heart and blood vessels, which includes: 1) hypertension (high blood pressure); 2) ischemic heart disease; 3) violation of cerebral circulation; 4) diseases of peripheral vessels; 5) heart failure; b) rheumatic heart diseases; 7) congenital heart defects; and 8) cardiomyopathy. Disorders of cerebral circulation, which can lead to heart attacks and strokes, develop mainly as a result of blockage of blood vessels, which prevents the flow of blood to the heart and brain. There are many causes of vascular occlusion and factors that influence vascular occlusion: among the causes of vascular occlusion, two are particularly common - thrombosis / thromboembolism and disorders of lipid metabolism, for example, atherosclerosis, as a result of dyslipidemia. Among the factors that affect the clogging of blood vessels, it is possible to single out a change in the rheological properties of blood and an increase/decrease in blood pressure.

Dyslipidemia is a disorder in which the level of cholesterol, in particular low-density lipoprotein cholesterol (LDL CHD), and/or triglycerides increases, or the level of high-density lipoprotein cholesterol (HDL CHD) in the blood plasma decreases, which leads to the development of atherosclerosis. Dyslipidemia has several types, including 1) pure or isolated hypercholesterolemia (increase of only cholesterol); 2) pure or isolated hypertriglyceridemia (increase in triglycerides only); and 3) combined or mixed hyperlipidemia (increased cholesterol and triglycerides). Also, dyslipidemia is divided into primary, that is, genetic, and secondary, caused by lifestyle and other factors.

Most cases of dyslipidemia in the adult population are secondary and are caused by a sedentary lifestyle, excessive consumption of saturated fats, cholesterol and trans-isomers of fatty acids, and to a lesser extent are the result of other diseases, excessive alcohol consumption, smoking, medication use, etc.

Hypercholesterolemia, as a type of dyslipidemia - a disorder in which the level of cholesterol in a person's blood increases significantly, especially such a type of cholesterol as cholesterol increases

From low-density lipoprotein (LDL). The increased level of cholesterol in the blood leads to the accelerated deposition of cholesterol on the inner walls of blood vessels, which leads to the formation of atherosclerotic plaques and the development of atherosclerosis. In atherosclerosis, the formation of atherosclerotic plaques on the inner walls of blood vessels that supply blood to the heart and brain leads to blockage of these vessels and the development of cardiovascular diseases, including heart attacks and strokes, coronary heart disease and peripheral vascular disease.

Thrombosis is a pathological condition caused by the formation of blood clots (clots) inside blood vessels and heart cavities, which prevent the free flow of blood through the circulatory system. At the same time, blood clots can circulate freely in the circulatory system (emboli) - thromboembolism, or attach to the inner walls of blood vessels (thrombi) - thrombosis.

One of the causes of thrombosis is platelet aggregation, that is, the sticking of platelets together to form blood clots (thrombus), or platelet adhesion, that is, their sticking to the inner walls of blood vessels. Therefore, the prevention of thrombosis is often aimed at reducing the adhesiveness and aggregation of platelets with the help of antiplatelet agents. Such antiplatelet agents include: 1) inhibitors of thromboxane A2, for example, acetylsalicylic acid; 2) phosphodiesterase inhibitors, such as dipyridamole; and 3) glycoprotein receptor inhibitors (eg, abciximab, tirofiban, lamifiban).

The processes of thrombus formation are especially actively manifested when the blood flow in the vessels is destabilized. For example, with atherosclerosis, an accelerated turbulent flow occurs in the area of the vessel narrowed by an atherosclerotic plaque, which leads to damage and development of endothelial dysfunction. Platelets contact the subendothelial structures of the damaged vascular wall, which causes their activation and leads to subsequent aggregation and adhesion.

Against the background of dyslipidemia, in particular hypercholesterolemia, and atherosclerosis, a number of cardiovascular diseases can develop, for example, such a type of thrombosis as arterial thrombosis (atherothrombosis), as well as thrombotic stroke.

The main cause of arterial thrombosis is damage to the walls of arteries by the formation of atherosclerotic plaques on them. The formation of atherosclerotic plaques by itself leads to progressive thickening of the arterial walls and narrowing of the lumen of the arteries. The main danger of arterial thrombosis lies in the rupture of the atherosclerotic plaque, in which platelet activation occurs. Platelets form a blood clot at the site of the tear

(thrombus), leading to artery occlusion, blockage of an artery by a blood clot, heart attack, stroke, heart attack, limb amputation, etc.

A stroke is a sudden and sharp disruption of the normal blood supply to the brain as a result of a rupture or blockage of blood vessels in the brain. Thrombotic stroke develops due to thrombosis of the arteries of the head and cerebral vessels against the background of pathological changes in their inner walls (most often due to the formation of atherosclerotic plaques). The formation of atherosclerotic plaques leads to stenosis, increased blood viscosity, increased albumin content and, as a result, changes in the protein coefficient of the blood. increase in blood coagulation activity, disturbances in central hemodynamics, in particular a decrease in blood pressure, slowing down of arterial blood flow. The gradual increase of the thrombus can lead to complete closure of the lumen of the vessel and occlusion.

Hypertension is a chronic disease in which there is a steady increase in hydraulic pressure in the arterial vessels of a large circle of blood circulation, caused by an increase in blood flow resistance, that is, the total peripheral resistance of blood vessels. Hypertension is a major risk factor for stroke, myocardial infarction (heart attack), heart failure, arterial aneurysms (such as aortic aneurysms), peripheral artery disease, and is a common cause of chronic kidney disease. Primary (essential) hypertension is the most common form of hypertension caused by factors such as poor diet, including high salt, fat and alcohol consumption, lack of physical activity, overweight and obesity, etc. At the same time, hypertension itself is a risk factor for the development of atherosclerosis, thrombosis, thromboembolism and a number of other CVDs, and vice versa, atherosclerosis, thrombosis, etc. are risk factors for the development of hypertension.

Hypertension can cause such diseases as vasorenal hypertension - secondary arterial hypertension, which occurs as a result of kidney ischemia followed by excessive release of renin; ischemic nephropathy - a decrease in glomerular filtration and impairment of other kidney functions as a result of hemodynamically significant narrowing of the renal artery; as well as chronic kidney failure - kidney dysfunction that occurs as a result of the death of nephrons (kidney cells) and their replacement by connective tissue. In addition, narrowing of the lumen of the renal vessels occurs mainly in older and elderly people

Caused by deposition of atherosclerotic plaques in blood vessels.

For the prevention, as well as treatment of disorders of lipid metabolism, cardiovascular complications and CVD, the WHO has defined a number of measures, which are divided into two types: 1) general measures, such as lifestyle changes, following a proper diet, reducing fat intake, increasing carbohydrate intake and fibers; increasing physical activity; and 2) individual measures, including the use of pharmaceutical compositions, such as pharmaceutical compositions containing aspirin, beta-blockers, angiotensin-converting enzyme inhibitors, and hypolipidemic pharmaceutical compositions. Currently, various approaches are used for the prevention and treatment of lipid metabolism disorders, cardiovascular complications, and CVD in general: 1) monotherapy with hypolipidemic pharmaceutical compositions based on statins; 2) prevention of thrombosis and thromboembolism due to the prevention of thrombus formation and changes in the rheological characteristics of blood using, for example, antiplatelet, antiplatelet, anticoagulation pharmaceutical compositions; 3) normalization of blood pressure to target levels using, for example, antihypertensive pharmaceutical compositions.

A very big drawback of the modern approach to the prevention and treatment of CVD in general, and the diseases, complications and disorders that cause CVD, in particular, is its one-sidedness. For the prevention and treatment of disorders of lipid metabolism, such as dyslipidemia, hypercholesterolemia, etc., hypolipidemic pharmaceutical compositions are used. Antihypertensive pharmaceutical compositions are used to treat hypertension, and antiplatelet, antiplatelet, anticoagulation pharmaceutical compositions are used to treat thrombosis and thromboembolism. At the same time, CVD can be caused not by one violation, but by several. That is, the patient needs to use several pharmaceutical compositions, which significantly negatively affects his adherence to treatment.

The special danger of CVDs arising on the background of disorders of lipid metabolism and cardiovascular complications lies in the fact that disorders of lipid metabolism and some cardiovascular complications associated with blood pressure are often asymptomatic. At the same time, the manifestation of acute ischemia due to the blockage of blood vessels occurs suddenly, causing a sudden clinical manifestation of CVD and the subsequent possible onset of death within a few hours against the background of the previous normal general state of health and the absence of health complaints. because Therefore, for CVD against the background of disorders of lipid metabolism and cardiovascular complications, it is not treatment, but prevention that is particularly important. At the same time, both prevention and treatment should be as simple as possible for the patient to follow.

The known hypolipidemic pharmaceutical composition ROSUVASTATIN-TEVA (see the web page at the address: pyrz//sotrepaiisht.sot.tsa/des/264940/) in an oral solid dosage form, namely in the form of a film-coated tablet containing 5 mg , 10 mg, 20 mg or 40 mg of rosuvastatin calcium, and auxiliary substances - microcrystalline cellulose, anhydrous lactose, crospovidone, povidone, sodium sterilfumarate, partially hydrolyzed polyvinyl alcohol, titanium dioxide, macrogol 3350, talc, iron oxide yellow, iron oxide black, yellow dye, iron oxide red, carmoisine, indigotine. The known pharmaceutical composition is intended for the treatment of hypercholesterolemia and prevention of cardiovascular disorders.

The well-known hypolipidemic pharmaceutical composition reliably reduces the frequency of CVD, in particular heart attacks and strokes, due to the reduction of the size of atherosclerotic plaques. However, the effectiveness of a known hypolipidemic pharmaceutical composition can be reduced to varying degrees depending on many factors, namely tolerance to rosuvastatin, gender specifics of the pharmacodynamics of rosuvastatin, obesity and overweight, high blood pressure, pH of gastric juice, motility of the gastrointestinal tract, concomitant diseases and pathologies (especially of the stomach and intestines, which can affect the absorption of rosuvastatin), etc. In such cases, it is necessary to select other hypolipidemic pharmaceutical compositions based on statins or use a combination of different pharmaceutical compositions that suppress the development of CVD by different mechanisms, for example, hypolipidemic pharmaceutical compositions, antiplatelet pharmaceutical compositions, and antihypertensive pharmaceutical compositions.

In addition, the known hypolipidemic pharmaceutical composition is characterized by insufficient efficiency. This is a consequence of the fact that for the prevention and treatment of CVD caused by various mechanisms, such as vascular occlusion due to the deposition of atherosclerotic plaques, vascular occlusion due to the formation of blood clots, increased blood pressure, it is advisable to use pharmaceutical compositions with different mechanisms, for example, hypolipidemic pharmaceutical compositions (based on statins), antiplatelet

Pharmaceutical compositions and antihypertensive pharmaceutical compositions. In this case, the probability of successful prevention and treatment of CVD against the background of lipid metabolism disorders increases.

In addition, as already noted, the pharmacokinetic properties of a known pharmaceutical composition can be adversely affected by the patient's high blood pressure. Since high blood pressure is a frequent companion of cardiovascular complications, for a certain group of patients the effectiveness of a known pharmaceutical composition may decrease and there will be a need to use additional pharmaceutical compositions.

In addition, in the case of unsatisfactory effectiveness of the individual use of a known pharmaceutical composition, the patient needs to use several pharmaceutical compositions, and this significantly affects the patient's commitment to treatment and the desire to adhere to the prescribed treatment regimen. At the same time, the patient's commitment to treatment is always a big problem and strongly depends on the organization of the treatment regimen itself, i.e. the need to visit the hospital, the number of pharmaceutical compositions that need to be used, the specific requirements for the use of each individual pharmaceutical composition, the ease/difficulty of distinguishing the dosage forms of each individual pharmaceutical compositions and probabilities of confusing the dosage forms of the pharmaceutical composition. Therefore, in the case of insufficient effectiveness for the prevention of CVD and the need to use a known pharmaceutical composition together with other pharmaceutical compositions, a significant problem with patient adherence to treatment will arise.

Thus, in the field of prevention and treatment of diseases associated with lipid metabolism disorders and CVD against the background of lipid metabolism disorders, there is an urgent need for new, effective, safe and convenient pharmaceutical compositions. At the same time, modern medical needs require a complex approach to the creation of pharmaceutical compositions, therefore it is rational to create pharmaceutical compositions that contain several active pharmaceutical ingredients with different mechanisms of action, and which combine different approaches to the prevention and treatment of diseases.

The task of a useful model is to create a pharmaceutical composition for the simultaneous prevention and/or treatment of essential hypertension and hypercholesterolemia, which are accompanied by the prevention of cardiovascular diseases, which is characterized by a convenient method of application, contributes to the improvement of the quality and standard of living of patients, which contributes to the patient's compliance with the treatment regimen and reducing the financial burden on the patient, as well as expanding the arsenal and assortment of pharmaceutical compositions for the simultaneous prevention and/or treatment of essential hypertension and hypercholesterolemia, which are accompanied by the prevention of cardiovascular diseases.

The task is solved by introducing five active pharmaceutical ingredients, which act by different mechanisms, in certain therapeutically effective doses determined by the doctor in one oral solid dosage form of the pharmaceutical composition.

The task is solved by creating a pharmaceutical composition in an oral solid dosage form containing rosuvastatin or its pharmaceutically acceptable salt and at least one excipient, while, according to a useful model, the composition additionally contains a chemical compound of the structural formula (I)

OUN ra schey SN" i o ,; () chemical compound of structural formula (II) or its prodrug form

N

"M. m M

20th centuries; did you hear ry av

M r , o-

M. 8;

M niv); (I) a chemical compound of the structural formula (I) or its pharmaceutically acceptable salt NN not M MN". and | 5 skin o o si Z

SNU

; (11) chemical compound of the structural formula (IM) (c) o, u ni ni on and magnesium hydroxide.

In addition, according to one of the variants of the useful model, the pharmaceutical composition contains rosuvastatin, a chemical compound of the structural formula (I), a chemical compound of the structural formula (I), a chemical compound of the structural formula (I), a chemical compound of the structural formula (IM) and magnesium hydroxide with the following number of components in one oral solid dosage form, in mg: rosuvastatin 5-50 chemical compound of structural formula I (1) 5О-200 chemical compound of structural formula 5-50 (II) chemical compound of structural formula 2-13 (PI)

a chemical compound of structural formula 5-50 (IM) magnesium hydroxide 5-50.

In addition, according to one of the variants of the utility model, the pharmaceutical composition contains rosuvastatin, a chemical compound of the structural formula (I), a chemical compound of the structural formula (I), a chemical compound of the structural formula (I), a chemical compound of the structural formula (IM) and magnesium hydroxide with the following number of components in one oral solid dosage form, in mg: rosuvastatin 20-40 chemical compound of structural formula 75-100 (I) chemical compound of structural formula 20-40 (II) chemical compound of structural formula 5-10 (IP) chemical compound structural 12.5-25 formula (IM) magnesium hydroxide 15-40.

In addition, according to one of the variants of the utility model, the composition is made in the form of a tablet covered with a shell.

In addition, according to one of the variants of the useful model, the composition is made in the form of a pill without a shell.

In addition, according to one of the variants of the useful model, the composition is made in the form of a capsule.

In addition, according to one of the variants of the utility model, as a pharmaceutically acceptable excipient, the composition contains at least one substance selected from the group: fillers, diluents, binders, disintegrants, lubricants, disintegrants, film formers, extenders, glazing agents , stabilizers, pigments, flavors and flavor additives.

In addition, according to one variant of the utility model, the composition as a pharmaceutically acceptable excipient contains at least one substance selected from the list: lactose monohydrate, hydroxypropyl cellulose microcrystalline, cellulose microcrystalline, hypromellose, mannitol, sodium lauryl sulfate, propylene glycol, talc, corn starch, starch potato, gelatinized starch, sodium starch glycolate, calcium hydrogen phosphate anhydrous, calcium phosphate, crospovidone, silicon dioxide colloidal anhydrous, magnesium stearate, stearic acid, glycerol triacetate, triacetin, titanium dioxide, quinoline yellow, iron oxide red.

In addition, according to one of the variants of the useful model, the pharmaceutical composition is used for the simultaneous prevention and/or treatment of essential hypertension and hypercholesterolemia, which are accompanied by the prevention of cardiovascular disorders, the treatment of stable chronic heart failure, the treatment of acute and chronic coronary heart disease, the prevention of repeated thrombosis, primary prevention of thrombosis and cardiovascular diseases.

Pharmaceutical composition - a combination of substances (one or more active pharmaceutical ingredients and auxiliary substances) that has properties and is intended for the treatment or prevention of diseases in humans. A pharmaceutical composition according to a useful model contains four active pharmaceutical ingredients in one oral solid dosage form, namely rosuvastatin or a pharmaceutically acceptable salt thereof, a chemical compound of structural formula (I), a prodrug form of a chemical compound of structural formula (II), a chemical compound of structural formula (II ) or a pharmaceutically acceptable salt thereof.

Rosuvastatin is a hypolipidemic agent and a selective and competitive inhibitor of the enzyme HMG-CoA reductase, which controls the rate of cholesterol synthesis in the cell and the synthesis of a number of other biologically active substances that are formed in the cells of the body from the same starting compounds as cholesterol. In addition, rosuvastatin increases the number of hepatic LDL-C receptors on the cell surface, increasing the capture and catabolism of LDL-C, and inhibits the synthesis of very low-density lipoprotein cholesterol (VLDL-C), thereby reducing the total number of LDL-C and LDL-C. In addition, rosuvastatin increases HO

LEFT As a result of the described mechanism, rosuvastatin helps to reduce the size of atherosclerotic plaques and increase the lumen of vessels.

According to one variant of the useful model, the pharmaceutical composition may contain a pharmaceutically acceptable salt of rosuvastatin, for example, rosuvastatin calcium, rosuvastatin magnesium, rosuvastatin zinc, rosuvastatin meglumine, etc.

In a pharmaceutical composition according to a useful model, rosuvastatin or its pharmaceutically acceptable salt is intended for the treatment of hypercholesterolemia, hypercholesterolemia with concomitant hypertriglyceridemia, hypercholesterolemia with concomitant diabetes.

The chemical compound of the structural formula (I) is an antiplatelet agent that irreversibly inhibits cyclooxygenase 1 (COX-1), including in platelets, and to a lesser extent inhibits cyclooxygenase 2 (COX-2). At the same time, the synthesis of prostaglandins, thromboxanes, especially thromboxane A2, and prostacyclins is inhibited. Since platelets do not contain a nucleus, the restoration of the formation of thromboxanes is possible only when new platelets enter the blood. In addition, the chemical compound of the structural formula (I) promotes the synthesis of lipoxins - mediators that have anti-inflammatory activity. As a result of the described mechanism, the chemical compound of structural formula (I) additionally acts as an analgesic and anti-inflammatory agent, and the manifestation of each action depends on the dose of the chemical compound of structural formula (1).

In the pharmaceutical composition according to the useful model, the chemical compound of the structural formula (I) is intended for the prevention of thrombosis and thromboembolism due to the reduction of platelet aggregation.

The chemical compound of the structural formula (II) is an antihypertensive agent that acts as a selective receptor antagonist (AT type) of angiotensin II, inhibits the action of angiotensin II, which is mediated by the ATI1 receptor, regardless of the source and pathway of angiotensin II synthesis.

Selective antagonism of AT receptors! of angiotensin II leads to an increase in plasma renin and concentrations of angiotensin I and angiotensin II, as well as to some decrease in the concentration of aldosterone in plasma. Due to the described mechanism of action, the chemical compound of the structural formula (III) causes a dose-dependent, long-term decrease in blood pressure.

In a pharmaceutical composition, the chemical compound of structural formula (II) can be an active chemical compound of structural formula (II) or a chemical compound of structural formula (II) in prodrug form.

The chemical compound of the structural formula (II) is an antihypertensive agent that performs a role

It is an antagonist of calcium ions (a blocker of slow calcium channels) and blocks the flow of calcium ions through the membranes to the cells of the smooth muscles of the myocardium and blood vessels. The mechanism of hypotensive action is caused by a direct effect on vascular smooth muscles. Due to the described mechanism, the chemical compound of the structural formula (II) expands peripheral arterioles and thus reduces the total peripheral resistance of blood vessels. Since the heart rate is practically unchanged, the reduction in the load on the heart leads to a decrease in energy consumption and myocardial oxygen demand. The chemical compound of the structural formula (II) also contributes to the expansion of coronary arterioles, both in intact and ischemic areas of the myocardium, which increases the supply of oxygen to the myocardium.

As part of a pharmaceutical composition according to a useful model, the chemical compound of the structural formula (IP) can be a mixture of two isomeric forms: 5 and ВН. In addition, in the composition of the pharmaceutical composition according to the useful model, the chemical compound of the structural formula (PI) can be a separate isomer: 5 or B. In addition, in the composition of the pharmaceutical composition according to the useful model, the chemical compound of the structural formula (II) can have the form of a pharmaceutically acceptable salt, for example hydrochloride, hydrobromide, sulfate, phosphate, acid phosphate, acetate, maleate, fumarate, lactate, tartrate, citrate, gluconate, besylate, tosylate, mesylate, succinate, salicylate, etc.

In a pharmaceutical composition according to a useful model, the chemical compound of the structural formula (I) or its prodrug form, and the chemical compound of the structural formula (I) or its pharmaceutically acceptable salt are intended to reduce blood pressure.

The chemical compound of the structural formula (IM) is a diuretic and antihypertensive agent that suppresses the adsorption of sodium and chlorine ions in the distal and proximal tubules; promotes the excretion of potassium, magnesium and water ions, retains calcium ions. The diuretic action of the chemical compound of structural formula (IM) causes a decrease in extracellular fluid volume, plasma volume, cardiac output, total sodium exchange, glomerular filtration rate, and renal plasma flow.

In a pharmaceutical composition according to a useful model, a chemical compound of the structural formula (IM) is used for the treatment of arterial hypertension, in particular, essential hypertension.

Additionally, the pharmaceutical composition may contain pharmaceutically acceptable excipients. The use of acceptable auxiliary substances for the manufacture of a pharmaceutical composition in an oral solid dosage form makes it possible to obtain a pharmaceutical composition in an oral solid dosage form, which is characterized by acceptable physicochemical indicators, organoleptic properties and good indicators of shelf life.

Any pharmaceutically acceptable substances known to specialists in the field of pharmacology can be used as pharmaceutically acceptable excipients, namely carriers, fillers, diluents, film formers, gelling agents, foaming agents, emulsifiers, stabilizers, solubilizers, plasticizers, binders, disintegrants, glidants substances, lubricants, disintegrants, film formers, extenders, glazing agents, stabilizers, pigments, flavorings and flavorings. As fillers, any fillers known to a specialist in the field of pharmacology can be used, for example, starches, sugars (sucrose, lactose, glucose, etc.), magnesium carbonate, magnesium oxide, sodium chloride, sodium hydrogen carbonate, kaolin, gelatin, cellulose (microcrystalline cellulose, methylcellulose, carboxymethylcellulose, etc.), dextrin, amylopectin, etc. Any binders known to a person skilled in the field of pharmacology can be used as binders, such as cellulose (carboxymethylcellulose, oxyethylcellulose, oxypropylmethylcellulose, etc.), alcohols (ethyl, polyvinyl, etc.), polyvinylpyrrolidone, alginic acid or alginates, etc. Any glidants known to a person skilled in the art of pharmacology can be used as glidants, such as starches, talc, polyethylene oxide, aerosil, etc. Any lubricants known to a person skilled in the art of pharmacology can be used as lubricants, such as magnesium or calcium stearate, stearic acid, etc. Lactose monohydrate, hydroxypropyl cellulose microcrystalline, microcrystalline cellulose, hypromellose, mannitol, sodium lauryl sulfate, propylene glycol, talc, corn starch, potato starch, pregelatinized starch, sodium starch glycolate, calcium hydrogen phosphate anhydrous, calcium phosphate are especially suitable for obtaining a pharmaceutical composition in an oral solid dosage form. , crospovidone, silicon dioxide colloidal anhydrous, magnesium stearate, stearic acid, glycerol triacetate, triacetin, titanium dioxide, quinoline yellow, iron oxide red.

One of the important components of the pharmaceutical composition according to the useful model is magnesium hydroxide. Magnesium hydroxide is both an auxiliary substance and an antacid agent, which

Zo reduces the development of side effects from the use of the chemical compound of structural formula (I) from the side of the gastrointestinal tract, that is, the development of erosive and ulcerative lesions of the stomach.

Magnesium hydroxide has a cytoprotective effect due to the increase of prostaglandins in the stomach wall, which reduces the likelihood of ulcers, and also increases the secretion of bicarbonates and increases the level of glycoproteins of gastric mucus. In addition, magnesium hydroxide (- an antiplatelet agent that changes the conformation of platelet membrane glycoproteins and prevents their binding to fibrin, reduces the synthesis of the thromboxane aggregation inducer Ag? and thus inhibits platelet aggregation. In addition, magnesium hydroxide can perform the role of a hypolipidemic agent for due to its effect on reducing the levels of triglycerides, LDL cholesterol and apoprotein B, as well as increasing the level of HDL cholesterol.

Rosuvastatin or its pharmaceutically acceptable salt in a pharmaceutical composition according to a useful model effectively reduces the level of LDL cholesterol, which contributes to the prevention of the development of hypercholesterolemia, atherosclerosis and, as a result, clogging of vessels with atherosclerotic plaques.

In a pharmaceutical composition, a combination of such agents as a chemical compound of the structural formula (I) and magnesium hydroxide is intended for the primary prevention of CVD, such as thrombosis and acute heart failure in the presence of risk factors (for example, diabetes, hyperlipidemia, arterial hypertension, obesity, smoking, old age), prevention of repeated myocardial infarction and thrombosis of blood vessels, prevention of thromboembolism, angina pectoris. In addition, the use of a combination of the chemical compound of the structural formula (I) and magnesium hydroxide is the most optimal option, since magnesium hydroxide, due to its rapid action, quickly and effectively neutralizes the negative effect of the chemical compound of the structural formula (I) on the walls of the stomach, and at the same time there is no negative influence on the absorption of the chemical compound of the structural formula (I). Therefore, the combination of the chemical compound of the structural formula (I) and magnesium hydroxide in the pharmaceutical composition according to a useful model allows to level the development of side effects from the gastrointestinal tract when using the pharmaceutical composition, for example, to prevent the development of dyspepsia, and to increase the patient's adherence to treatment.

The combination of the chemical compound of the structural formula (II) or its prodrug form, and the chemical compound of the structural formula (II) or its pharmaceutically acceptable salt provides a synergistic antihypertensive effect, which provides a reduction in blood pressure to a greater extent than when using each of them separately.

The chemical compound of the structural formula (IM) provides a decrease in the volume of circulating blood and cardiac output with an insignificant increase in peripheral resistance. With further use, the chemical compound of the structural formula (IM) reduces peripheral vascular resistance, which leads to a steady decrease in blood pressure.

The oral solid dosage form of the pharmaceutical composition can be a coated tablet, a tablet without a coating, or a capsule. Oral solid dosage forms of pharmaceutical compositions with different contents of active pharmaceutical ingredients can be colored in different colors and/or have different letter designations and/or have different numerical designations and/or have different shapes.

Thus, a pharmaceutical composition according to a useful model in an oral solid dosage form, which contains a combination of five different active pharmaceutical ingredients, provides the simultaneous prevention and/or treatment of essential hypertension and hypercholesterolemia, which are accompanied by the prevention of cardiovascular disorders, the treatment of stable chronic heart failure , treatment of acute and chronic coronary heart disease, prevention of repeated thrombus formation, primary prevention of thrombosis and cardiovascular diseases. This effect is achieved due to the complex action of the pharmaceutical composition according to a useful model, since rosuvastatin prevents the narrowing of the vessel lumen by reducing the deposition of atherosclerotic plaques in the vessels, the chemical compound of the structural formula (I) and magnesium hydroxide prevent the narrowing of the vessel lumen by preventing the formation of blood clots, a combination of chemical the compound of the structural formula (II) and the chemical compound of the structural formula (II) lowers blood pressure in blood vessels, and the chemical compound of the structural formula (IM) reduces the volume of circulating blood. Thus, the pharmaceutical composition provides effective prevention of cardiovascular diseases, in particular those accompanied by blockage of blood vessels and ischemia due to blockage of blood vessels.

Example 1

Stage 1. Sifting. Lactose monohydrate, corn starch, propyl gallate, disodium

Z edetate is sieved until it passes through a 40-mesh sieve, rosuvastatin, chemical compound of structural formula (I), prodrug form of chemical compound of structural formula (II), besylate of chemical compound of structural formula (II), chemical compound of structural formula (IM), magnesium stearate and the purified talc is sieved until it passes through a 60-mesh sieve.

Stage 2. Dry mixing. Sifted lactose monohydrate - 9.154 kg, corn starch - 6.860 kg, propyl gallate - 0.003 kg, and disodium edetate - 0.0029 kg, magnesium hydroxide - 4.08 kg, calcium rosuvastatin - 1.04 kg are transferred to a high-speed mixer-granulator and mixed for 10.0 min at slow speeds.

Stage 3. Preparation of starch paste. Purified water (10 kg) is heated to 90 °C in a pasta preparation vessel equipped with a heating jacket. Corn starch (1,950 kg) is sieved through a 60 mesh sieve into a vessel with pasta preparation water and mixed for 2 minutes to obtain a homogeneous suspension. the suspension is filtered through a 120-mesh nylon cloth into a clean stainless steel container. The suspension is transferred to a clean stainless steel container and cooled to 37 "C.

Stage 4. Obtaining granules. The paste obtained in step 3 is added to the mixture obtained in step 2 in a high-speed mixer-granulator and mixed for 10 minutes until granules are obtained. The wet granules are transferred to a fluidized bed dryer and dried for 30 minutes at 65 °C. All dried granules are sieved through a 12-mesh sieve, and the granules that did not pass through the sieve are ground in a mill equipped with a 1.0 mm sieve. after which the pellets are passed through a screening machine with a 12-mesh screen. This operation is repeated until all the pellets pass through a 12-mesh screen. The pellets of the required size are dried in a fluidized bed dryer to a residual moisture content of no more than 95 wt.

The temperature at the entrance to the dryer is 65 "C, at the exit - 38 "C, the drying time is 30 minutes.

Stage 5. Powdering. The dried granules are transferred to an octagonal mixer and mixed for 5 minutes. Purified talc (0.29 kg), magnesium stearate (0.29 kg), chemical compound of structural formula (I) (7.5 kg), prodrug form of chemical compound of structural formula (II) (2.0 kg) are added to the mixer. and besylate of chemical compound of structural formula (III) (0.69 kg), chemical compound of structural formula (IM) (1.25 kg) and mixed for 15 minutes.

Stage 6. Tableting. Powdered granules are tableted, according to the technological regulations, on any acceptable tablet machine to obtain tablet cores.

Stage 7. Preparation of a solution for coating tablets. Purified water (35.0 kg) is poured into a stainless steel container, hydroxypropylmethylcellulose (0.36 kg), polyethylene glycol РЕС 6000 (0.10 kg) and purified talc (0.10 kg) are added while stirring. The mixture is stirred for 10 minutes. Purified water (35.0 kg) is poured into another stainless steel container, titanium dioxide (0.24 kg) and red iron oxide (0.02 kg) are added while stirring. The mixture is stirred for 20 minutes. The first solution is poured into the second solution with constant stirring until a homogeneous solution is obtained for coating the tablets.

Stage 8. Covering the tablets with a shell. The cores of the tablets are loaded into the high-speed mixer-granulator and the solution for coating the tablets is added with constant stirring at low speeds. Stirring lasts 10 minutes.

In this way, a pharmaceutical composition is obtained in an oral solid dosage form, namely in the form of a tablet covered with a shell, which contains 5 mg of rosuvastatin, 75 mg of the chemical compound of the structural formula (I) and 15.2 mg of magnesium hydroxide, 20 mg of the prodrug form of the chemical compound of the structural formula of the formula (I) and 6.9 mg of besylate of the chemical compound of the structural formula (II) (which is equivalent to 5 mg of the chemical compound of the structural formula (PI)), 12.5 mg of the chemical compound of the structural formula (IM).

Example 2

Stage 1. Sifting. Lactose monohydrate, corn starch, propyl gallate, disodium edetate are sifted until completely passing through a 40 mesh sieve, rosuvastatin, chemical compound of structural formula (I), prodrug form of chemical compound of structural formula (II), besylate of chemical compound of structural formula (II), chemical compound of the structural formula (IM), magnesium stearate and purified talc are sifted until completely passing through a 60 mesh sieve.

Stage 2. Dry mixing. Sifted lactose monohydrate - 9.154 kg, corn starch - 6.860 kg, propyl gallate - 0.003 kg, and disodium edetate - 0.0029 kg, magnesium hydroxide - 4.08 kg, calcium rosuvastatin - 2.08 kg are transferred to a high-speed mixer-granulator and mixed for 10.0 min at slow speeds.

Stage 3. Preparation of starch paste. Purified water (10 kg) is heated to 90 °C in a pasta preparation vessel equipped with a heating jacket. Corn starch (1,950 kg) is sieved through a 60-mesh sieve into a pasta preparation water vessel and mixed.

For 2 minutes to obtain a homogeneous suspension. The resulting suspension is filtered through a 120-mesh nylon cloth into a clean stainless steel container. The suspension is transferred to a clean stainless steel container and cooled to 37 °C.

Stage 4. Obtaining granules. The paste obtained in step 3 is added to the mixture obtained in step 2 in a high-speed mixer-granulator and mixed for 10 minutes until granules are obtained. The wet granules are transferred to a fluidized bed dryer and dried for 30 minutes at 65 °C. All dried granules are sieved through a 12-mesh sieve, and the granules that did not pass through the sieve are ground in a mill equipped with a 1.0 mm sieve. after which the pellets are passed through a screening machine with a 12-mesh screen. This operation is repeated until all the pellets pass through a 12-mesh screen. The pellets of the required size are dried in a fluidized bed dryer to a residual moisture content of no more than 95 wt.

The temperature at the entrance to the dryer is 65 "C, at the exit - 38 "C, the drying time is 30 minutes.

Stage 5. Powdering. The dried granules are transferred to an octagonal mixer and mixed for 5 minutes. Purified talc (0.29 kg), magnesium stearate (0.29 kg), chemical compound of structural formula (I) (7.5 kg), prodrug form of chemical compound of structural formula (II) (4.0 kg) are added to the mixer. and the besylate of the chemical compound of the structural formula (III) (1.38 kg), the chemical compound of the structural formula (IM) (2.5 kg) and stirred for 15 minutes.

Stage 6. Tableting. Powdered granules are tableted, according to the technological regulations, on any acceptable tablet machine to obtain tablet cores.

Stage 7. Preparation of a solution for coating tablets. Purified water (35.0 kg) is poured into a stainless steel container, hydroxypropylmethylcellulose (0.36 kg), polyethylene glycol РЕС 6000 (0.10 kg) and purified talc (0.10 kg) are added while stirring. The mixture is stirred for 10 minutes. Purified water (35.0 kg) is poured into another stainless steel container, titanium dioxide (0.24 kg) and red iron oxide (0.02 kg) are added while stirring. The mixture is stirred for 20 minutes. The first solution is poured into the second solution with constant stirring until a homogeneous solution is obtained for coating the tablets.

Stage 8. Covering the tablets with a shell. The cores of the tablets are loaded into the high-speed mixer-granulator and the solution for coating the tablets is added with constant stirring at low speeds. Stirring lasts 10 minutes.

In this way, a pharmaceutical composition is obtained in an oral solid dosage form, namely in the form of a tablet covered with a shell, which contains 10 mg of rosuvastatin, 75 mg of the chemical compound of the structural formula (I) and 15.2 mg of magnesium hydroxide, 40 mg of the prodrug form of the chemical compound of the structural formula (II) and 13.8 mg of besylate of the chemical compound of the structural formula (II) (which is equivalent to 10 mg of the chemical compound of the structural formula (III)), 25 mg of the chemical compound of the structural formula (IM).

Example C

Stage 1. Sifting. Lactose monohydrate, corn starch, propyl gallate, disodium edetate are sifted until completely passed through a 40 mesh sieve, rosuvastatin, chemical compound of structural formula (I), prodrug form of chemical compound of structural formula (II), besylate of chemical compound of structural formula (II), chemical compound of the structural formula (IM), magnesium stearate and purified talc are sifted until completely passing through a 60 mesh sieve.

Stage 2. Dry mixing. Sifted lactose monohydrate - 9.154 kg, corn starch - 6.860 kg, propyl gallate - 0.003 kg, and disodium edetate - 0.0029 kg, magnesium hydroxide - 6.07 kg, rosuvastatin calcium - 4.16 kg are transferred to a high-speed mixer-granulator and mixed for 10.0 min at slow speeds.

Stage 3. Preparation of starch paste. Purified water (10 kg) is heated to 90 °C in a pasta preparation vessel equipped with a heating jacket. Corn starch (1,950 kg) is sieved through a 60 mesh sieve into a vessel with pasta preparation water and mixed for 2 minutes to obtain a homogeneous suspension. the suspension is filtered through a 120-mesh nylon cloth into a clean stainless steel container. The suspension is transferred to a clean stainless steel container and cooled to 37 "C.

Stage 4. Obtaining granules. The paste obtained in step 3 is added to the mixture obtained in step 2 in a high-speed mixer-granulator and mixed for 10 minutes until granules are obtained. The wet granules are transferred to a fluidized bed dryer and dried for 30 minutes at 65 °C. All dried granules are sieved through a 12-mesh sieve, and the granules that did not pass through the sieve are ground in a mill equipped with a 1.0 mm sieve. after which the pellets are passed through a screening machine with a 12-mesh screen. This operation is repeated until all the pellets pass through a 12-mesh screen. The pellets of the required size are dried in a fluidized bed dryer to a residual moisture content of no more than 95 wt.

The temperature at the entrance to the dryer is 65 "C, at the exit - 38 "C, the drying time is 30 minutes.

From Stage 5. Powdering. The dried granules are transferred to an octagonal mixer and mixed for 5 minutes. Purified talc (0.29 kg), magnesium stearate (0.29 kg), chemical compound of structural formula (I) (10.0 kg), prodrug form of chemical compound of structural formula (II) (2.0 kg) are added to the mixer. and besylate of chemical compound of structural formula (III) (0.69 kg), chemical compound of structural formula (IM) (1.25 kg) and mixed for 15 minutes.

Stage 6. Tableting. Powdered granules are tableted, according to the technological regulations, on any acceptable tablet machine to obtain tablet cores.

Stage 7. Preparation of a solution for coating tablets. Purified water (35.0 kg) is poured into a stainless steel container, hydroxypropylmethylcellulose (0.36 kg), polyethylene glycol РЕС 6000 (0.10 kg) and purified talc (0.10 kg) are added while stirring. The mixture is stirred for 10 minutes. Purified water (35.0 kg) is poured into another stainless steel container, titanium dioxide (0.24 kg) and red iron oxide (0.02 kg) are added while stirring. The mixture is stirred for 20 minutes. The first solution is poured into the second solution with constant stirring until a homogeneous solution is obtained for coating the tablets.

Stage 8. Covering the tablets with a shell. The cores of the tablets are loaded into the high-speed mixer-granulator and the solution for coating the tablets is added with constant stirring at low speeds. Stirring lasts 10 minutes.

In this way, a pharmaceutical composition is obtained in an oral solid dosage form, namely in the form of a tablet covered with a shell, which contains 20 mg of rosuvastatin, 100 mg of the chemical compound of the structural formula (I) and 30.39 mg of magnesium hydroxide, 20 mg of the prodrug form of the chemical compound of the structural formula of the formula (I) and 6.9 mg of besylate of the chemical compound of the structural formula (II) (which is equivalent to 5 mg of the chemical compound of the structural formula (P)), 12.5 mg of the chemical compound of the structural formula (IM).

Example 4

Stage 1. Sifting. Lactose monohydrate, corn starch, propyl gallate, disodium edetate are sifted until completely passed through a 40 mesh sieve, rosuvastatin, chemical compound of structural formula (I), prodrug form of chemical compound of structural formula (II), besylate of chemical compound of structural formula (II), chemical compound of the structural formula (IM), magnesium stearate and purified talc are sifted until completely passing through a 60 mesh sieve.

Stage 2. Dry mixing. Sifted lactose monohydrate - 9.154 kg, corn starch - 60 6.860 kg, propyl gallate - 0.003 kg, and disodium edetate - 0.0029 kg, magnesium hydroxide - 6.07 kg,

rosuvastatin calcium - 8.32 kg is transferred to a high-speed mixer-granulator and mixed for 10.0 min at slow speeds.

Stage 3. Preparation of starch paste. Purified water (10 kg) is heated to 90 °C in a pasta preparation vessel equipped with a heating jacket. Corn starch (1,950 kg) is sieved through a 60 mesh sieve into a vessel with pasta preparation water and mixed for 2 minutes to obtain a homogeneous suspension. the suspension is filtered through a 120-mesh nylon cloth into a clean stainless steel container. The suspension is transferred to a clean stainless steel container and cooled to 37 "C.

Stage 4. Obtaining granules. The paste obtained in step 3 is added to the mixture obtained in step 2 in a high-speed mixer-granulator and mixed for 10 minutes until granules are obtained. The wet granules are transferred to a fluidized bed dryer and dried for 30 minutes at 65 °C. All dried granules are sieved through a 12-mesh sieve, and the granules that did not pass through the sieve are ground in a mill equipped with a 1.0 mm sieve. after which the pellets are passed through a screening machine with a 12-mesh screen. This operation is repeated until all the pellets pass through a 12-mesh screen. The pellets of the required size are dried in a fluidized bed dryer to a residual moisture content of no more than 95 wt.

The temperature at the entrance to the dryer is 65 "C, at the exit - 38 "C, the drying time is 30 minutes.

Stage 5. Powdering. The dried granules are transferred to an octagonal mixer and mixed for 5 minutes. Purified talc (0.29 kg), magnesium stearate (0.29 kg), chemical compound of structural formula (I) (10.0 kg), prodrug form of chemical compound of structural formula (II) (4.0 kg) are added to the mixer. and the besylate of the chemical compound of the structural formula (III) (1.38 kg), the chemical compound of the structural formula (IM) (2.5 kg) and mixed for 15 minutes.

Stage 6. Tableting. Powdered granules are tableted according to the technological regulations, on any acceptable tablet machine for obtaining tablet cores.

Stage 7. Preparation of a solution for coating tablets. Purified water (35.0 kg) is poured into a stainless steel container, hydroxypropylmethylcellulose (0.36 kg), polyethylene glycol РЕС 6000 (0.10 kg) and purified talc (0.10 kg) are added while stirring. The mixture is stirred for 10 minutes. Purified water (35.0 kg) is poured into another stainless steel container, titanium dioxide (0.24 kg) and red iron oxide (0.02 kg) are added while stirring. Mixture

It is stirred for 20 minutes. The first solution is poured into the second solution with constant stirring until a homogeneous solution is obtained for coating the tablets.

Stage 8. Covering the tablets with a shell. The cores of the tablets are loaded into the high-speed mixer-granulator and the solution for coating the tablets is added with constant stirring at low speeds. Stirring lasts 10 minutes.

In this way, a pharmaceutical composition is obtained in an oral solid dosage form, namely in the form of a tablet covered with a shell, which contains 40 mg of rosuvastatin, 100 mg of the chemical compound of the structural formula (I) and 30.39 mg of magnesium hydroxide, 40 mg of the prodrug form of the chemical compound of the structural formula of the formula (II) and 1.38 mg of besylate of the chemical compound of the structural formula (II) (which is equivalent to 10 mg of the chemical compound of the structural formula (III)), 25 mg of the chemical compound of the structural formula (IM).

Example 5

A clinical study was conducted to determine the effect of such an active pharmaceutical ingredient of a pharmaceutical composition according to a useful model, as rosuvastatin, on the level of total cholesterol and LDL cholesterol. The first phase of the study would last weeks and involve a low-fat diet. The second stage of the study was 12 weeks and represented a randomized stage of the study, in which all participants were randomized into 4 groups: 1) 5 mg rosuvastatin; 2) 10 mg rosuvastatin; 3) 20 mg rosuvastatin; 4) placebo. The third stage of the study was 40 weeks and represented an open stage of the study, during which all participants were selected an effective dose of rosuvastatin, which was subsequently used.

In the 6th week of the second stage of the study, the percentage of LDL cholesterol in the first group decreased by 40.195, in the second group by 45.4%, in the third group by 49.8%, and in the fourth group by 0.8%. At the end of the 12th week of the second stage of the study, the average percentage of CS LIINSH in the first group decreased by 38.3 95, in the second group - by 44.6 95, in the third group - by 50.0 95, in the fourth group - by 0.7 Uo . At the same time, at the end of the 12th week of the second stage, the average percentage of CS LIPVS in the first group decreased by 2.7 units, in the second group it increased by 4.395, in the third group it increased by 2.090; the level of triglycerides in the first group decreased by 4.8 Fo, in the second group - by 18.7 95, in the third group - by 13.2 Fo. At the end of the 52nd week of the study, 41,95 people had an average LDL-C level of less than 1.10 mg/ml, and 53,9 people had an average LDL-C level of less than 1.30 mg/ml.

Therefore, the conducted clinical study confirms the effectiveness of using such an active pharmaceutical ingredient of a pharmaceutical composition according to a useful model, as rosuvastatin, for reducing the level of triglycerides and preventing disorders of lipid metabolism.

Example 6

A study was conducted to determine the effectiveness of such an active pharmaceutical ingredient of the composition according to a useful model, as a chemical compound of the structural formula (I) for the primary prevention of cardiovascular complications.

All study participants were randomized at a ratio of 1:1 into two groups: the first group received a chemical compound of structural formula (I) in the amount of 100 mg once a day; the second group received a placebo once a day. The efficiency indicator is the time to the first fatal case from a cardiovascular complication, myocardial infarction, unstable angina, stroke, transient ischemic attack.

Fatal cases from cardiovascular complications, myocardial infarction, unstable angina, stroke, transient ischemic attack occurred in 4.29 95 participants from the first group and 4.48 95 participants from the second group. Cases of gastrointestinal bleeding were observed in 0.97% of participants from the first group and in 0.46% of 95 participants from the second group. The overall incidence of side effects was similar in both groups: 82.01 95 and 81.72 95, for the first and second groups, respectively. At the same time, the overall frequency of serious side effects was also similar for both groups: 20.19 F and 20.89 95, for the first and second groups, respectively.

Therefore, the conducted research indicates that the use of such an active pharmaceutical ingredient of a pharmaceutical composition according to a useful model, as a chemical compound of the structural formula (I) is safe and helps prevent platelet aggregation, as evidenced by the frequency of gastrointestinal bleeding.

Example 7

A study was conducted to determine the effectiveness of such active pharmaceutical ingredients as the chemical compound of the structural formula (II) in prodrug form and the chemical compound of the structural formula (II) on reducing blood pressure.

Study participants were randomized into four groups: 1) 40 mg of the chemical compound of structural formula (II) in prodrug form once a day; 2) 10 mg of a chemical compound

From the structural formula (II) once a day; 3) 40 mg of the chemical compound of the structural formula (II) in prodrug form and 10 mg of the chemical compound of the structural formula (I) once a day; 4) placebo.

The performance indicator is the change in systolic and diastolic blood pressure compared to the initial level.

After 8 weeks of the study, the level of systolic blood pressure decreased by an average of 20 mm Hg. Art. in the first group, by 15 mm Hg. Art. - in the second group; at 30 mm Hg. Art. - in the third group, and by 5 mm. mercury Art. in the fourth group. The level of systolic blood pressure decreased by an average of 10 mm Hg. Art. in the first group, by 13 mm Hg. Art. - in the second group; at 20 mm Hg Art. - in the third group, and by 5 mm. mercury Art. in the fourth group.

Therefore, the conducted study indicates that the combination of such active pharmaceutical ingredients as the chemical compound of the structural formula (II) in the prodrug form and the chemical compound of the structural formula (II) effectively lowers blood pressure and is more effective than each individual active pharmaceutical ingredient .

Example 8

A clinical study was conducted among persons over 65 years of age with diagnosed hypertension to determine the blood pressure-lowering effect of such an active pharmaceutical ingredient of a useful model pharmaceutical composition as a chemical compound of structural formula (IM).

For 4 weeks, the study participants used the chemical compound of structural formula (IM) 2 in the amount of 25 mg, once a day. After 4 weeks of the study, the participants experienced a decrease in systolic blood pressure at rest by an average of 13 mm Hg. and diastolic blood pressure - by 17 mm Hg.

Therefore, the conducted study shows that such an active pharmaceutical ingredient of a pharmaceutical composition according to a useful model, as a chemical compound of the structural formula (IM), effectively reduces blood pressure in patients.

The given examples are only intended to illustrate a useful model and are not limiting in any way.

The technical result achieved by the useful model is as follows:

The pharmaceutical composition according to the useful model is characterized by a convenient method of application, since it is in an optimal oral solid dosage form, namely in the form of a tablet or capsule, suitable for easy and painless swallowing. In addition, the optimal qualitative and quantitative composition of the pharmaceutical composition, namely the presence in one oral dosage form of a hypolipidemic agent - rosuvastatin or its pharmaceutically acceptable salt, an antiplatelet agent - a chemical compound of the structural formula (I), antihypertensive agents - a chemical compound of the structural formula (II) , or its prodrug form, and the chemical compound of the structural formula (I), or its pharmaceutically acceptable salt, of the chemical compound of the structural formula (IM) in specific therapeutically effective doses determined by the doctor allows to maximally simplify the use of the pharmaceutical composition according to the useful model. The proposed range of therapeutic doses allows the patient to easily switch from one pharmaceutical composition to another if necessary to increase or decrease the therapeutic dose to achieve the target therapeutic effect.

The pharmaceutical composition according to the useful model contributes to improving the quality and standard of life of the patient, which contributes to the patient's compliance with the treatment regimen and reduces the financial burden on the patient due to the introduction into one oral solid dosage form of a hypolipidemic agent - rosuvastatin or its pharmaceutically acceptable salt, an antiplatelet agent - a chemical compound of structural formula (I) and antihypertensive agents - a chemical compound of the structural formula (II), or its prodrug form, and a chemical compound of the structural formula (IP), or its pharmaceutically acceptable salt, a chemical compound of the structural formula (IM) in specific therapeutically effective doses determined by the doctor .

The absence of the need to use several pharmaceutical compositions in an oral solid dosage form significantly contributes to the patient's adherence to treatment and increases the desire to adhere to the treatment regimen. In addition, the pharmaceutical composition according to the useful model can be used for clinical and non-clinical treatment, which further simplifies the treatment regimen and increases the desire to adhere to the prescribed treatment regimen.

The pharmaceutical composition according to the useful model helps to reduce the financial burden on the patient due to the use of only one pharmaceutical composition in an oral solid dosage form instead of several separate pharmaceutical compositions in an oral solid dosage form, which further promotes compliance with the treatment regimen.

A pharmaceutical composition based on a useful model allows you to expand your arsenal and

From the assortment of pharmaceutical compositions for the simultaneous prevention and treatment of essential hypertension and hypercholesterolemia, accompanied by the prevention of cardiovascular disorders, due to the fact that it is proposed to introduce into one oral solid dosage form a hypolipidemic agent - rosuvastatin or its pharmaceutically acceptable salt, an antiplatelet agent - a chemical compound of the structural formula (I) and antihypertensive agents - the chemical compound of the structural formula (II), or its prodrug form, and the chemical compound of the structural formula (II), or its pharmaceutically acceptable salt, the chemical compound of the structural formula (IM) in specific therapeutically effective doses determined by the doctor doses

Claims (9)

40 USEFUL MODEL FORMULA 1. A pharmaceutical composition in an oral solid dosage form containing rosuvastatin or its pharmaceutically acceptable salt and at least one excipient, which is characterized by the fact that it additionally contains a chemical compound of the structural formula (I) be On u SU shk AN an) chemical compound of the structural formula (II) or its prodrug form N M. M M XK -0 la t shk B; m / I; SHHA a o u Kk ut m-y Z o-u i Okh hi o M 7 no ; (I) a chemical compound of the structural formula (I) or its pharmaceutically acceptable salt o not o 0) si With sn. ; (TP) a chemical compound of the structural formula (IM) (6) oh, what? on si (M) and magnesium hydroxide. 2. Pharmaceutical composition according to claim 1, which is characterized by containing rosuvastatin, a chemical compound of the structural formula (I), a chemical compound of the structural formula (I), a chemical compound of the structural formula (II), a chemical compound of the structural formula (IM) and magnesium hydroxide , with the following number of components in one oral solid dosage form, in mg: rosuvastatin 5-50 chemical compound of structural Yua. formula (I) 5O-200 chemical compound of structural formula 5-50 (II) chemical compound of structural formula 2-13 (IP) chemical compound of structural formula 5-50 (IM) magnesium hydroxide 5-50. C. A pharmaceutical composition according to any of claims 1, 2, which is characterized in that the pharmaceutical composition contains rosuvastatin, a chemical compound of the structural formula (1), a chemical compound of the structural formula (II), a chemical compound of the structural formula (I), a chemical compound of structural formula (IM) and magnesium hydroxide, with the following number of components in one oral solid dosage form, in mg: rosuvastatin 20-40 chemical compound of structural formula (I) 75-100 chemical compound of structural zd. formulas (II) 20-40 chemical compound of structural formula 5-10 (IP) chemical compound of structural formula I (IM) 12.5-25 magnesium hydroxide 15-40. 4. Pharmaceutical composition according to any of claims 1-3, which differs in that it is made in the form of a tablet covered with a shell. 5. Pharmaceutical composition according to any of claims 1-3, which differs in that it is made in the form of a tablet without a shell. 6. Pharmaceutical composition according to any of claims 1-3, which differs in that it is made in the form of a capsule. 7. Pharmaceutical composition according to any one of claims 1-6, which is characterized by the fact that, as a pharmaceutically acceptable excipient, it contains at least one substance selected from the group: fillers, diluents, binders, disintegrants, glidants, lubricants, disintegrants, film formers, extenders, glazing agents, stabilizers, pigments, aromas and flavor additives. 8. Pharmaceutical composition according to claim 7, which is characterized by the fact that as a pharmaceutically acceptable excipient it contains at least one substance selected from the list: lactose monohydrate, hydroxypropyl cellulose microcrystalline, cellulose microcrystalline, hypromellose, mannitol, sodium lauryl sulfate, propylene glycol, talc, corn starch, potato starch, gelatinized starch, sodium starch glycolate, calcium hydrogen phosphate anhydrous, calcium phosphate, crospovidone, colloidal anhydrous silicon dioxide, magnesium stearate, stearic acid, glycerol triacetate, triacetin, titanium dioxide, quinoline yellow, iron oxide red. 9. Pharmaceutical composition according to any of claims 1-9, which is characterized by the fact that it is used for the simultaneous prevention and/or treatment of essential hypertension and hypercholesterolemia, which are accompanied by the prevention of cardiovascular disorders, the treatment of stable chronic heart failure, the treatment of acute and chronic ischemic heart disease, prevention of repeated thrombus formation, primary prevention of thrombosis and cardiovascular diseases.