EA025844B1 - Means for correction of hypercholesterolemia - Google Patents

Abstract

A means for hypercholesterolemia correction is related to chemico-pharmaceutical industry, in particular, to providing a pharmaceutical composition having hypolipidemic activity that can be used as a means for normalizing the cholesterol level in human blood, or can find application in cardiology for atherosclerosis prophylaxis and treatment. The proposed means for hypercholesterolemia correction includes 0.05 mg of selenomethionine, 10 mg of vitamin E and pharmaceutically active additives, namely, microcrystal cellulose, ascorbic acid, magnesium stearate and methyl cellulose in pharmaceutically acceptable amounts. When using said means, people with hypercholesterolemia show a decrease in cholesterol level of blood serum by up to 37.5% accompanied by a tendency for normalizing the proportion of concentrations of high-density lipoproteins (HDLP) and low-density lipoproteins (LDLP).

Description

The invention relates to the pharmaceutical industry, in particular to the creation of a pharmaceutical composition having lipid-lowering activity, which can be used as a means to normalize cholesterol levels in human blood or can be used in cardiology for the prevention and treatment of atherosclerosis.

Among the causes of mortality, diseases of the cardiovascular system are leading, which is associated with lifestyle, heredity, environment and nutritional status of a person. The point of application of these predisposing factors is the occurrence of atherosclerosis. An important role in the pathogenesis of this disease is played by hyperlipidemia, in particular, an increase in cholesterol (cholesterol), low and very low density lipoproteins (LDL, VLDL), triglycerides (TG), apolipoprotein B, as well as a decrease in high density lipoprotein (HDL) in the blood and their transport proteins of apolipoproteins A. These biochemical changes cause lipid infiltration of the vascular endothelium, which directly leads to atherosclerotic vascular damage and impaired blood circulation in the affected arteries. Cholesterol enters the human body both from the outside and is synthesized in the body by liver cells, being an important structural component of cell membranes. The synthesis of cholesterol in the liver is simplified as follows: 3 hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) is synthesized from 3 molecules of acetate and coenzyme A, and under the action of the enzyme HMG-CoA reductase, mevalonic acid is formed from it, which (after about 20 cycles) turns into a cholesterol. The key step in this chain is the enzyme HMG-CoA reductase. The main atherogenic class are LDL, which contain about 60-70% of total plasma cholesterol and contribute to its penetration into cells. Being in the bloodstream, they are oxidized and captured by macrophages, forming foamy cells - substrates of plaques. HDLP, which carries out the reverse transport of excess cholesterol from cells, has the opposite effect.

Hypercholesterolemia is one of the main risk factors for the development of atherosclerosis and its complications. This risk increases in proportion to an increase in LDL. To determine the nature and intensity of lipid-lowering therapy, the determination of the level of total cholesterol and the ratio of LDL to HDL is of primary importance. When treating a particular patient, it is necessary to both reduce the level of total cholesterol and optimize the ratio of LDL to HDL.

The major successes achieved in the treatment and prevention of atherosclerosis are mainly associated with the use of completely new, specially developed, medicines for this purpose. In total, there are 4 classes of drugs that lower LDL and have proven their antiatherosclerotic effect. These include slow-release nicotinic acid preparations, bile acid sequestrants, fibrates, and statins.

Among these drugs, statins are considered the most effective and safe, indicated for the vast majority of patients with atherosclerotic diseases. Several types of statins are known: such as atorvastatin, cerivastatin, fluvastatin, lovastatin, mevastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin. In clinical practice, either clinical drugs that block the activity of the enzyme hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase) statins (simvastatin, lovastatin, fluvastatin, atorvostatin, rosuvastatin, etc.) are used as the main methods of correction of elevated serum cholesterol in blood serum. drugs that inhibit the absorption of cholesterol and sterols in the intestine (ezetimibe) (Clinical recommendations. Cardiology, under the editorship of Yu.N. Belenkov, RG Oganova. - M .: GEOTAR-Media, 2007. - 640 p. Diagnosis and correction lipid disorders exchange for the prevention and treatment of atherosclerosis. Brief Russian recommendations. M: 2005. - 20 pp. Diagnosis and treatment of stable angina. Russian recommendations (second revision). - M .: 2008. - 40 p. Perova N.V., Metelskaya VA Metabolic disorders in the pathogenesis of atherosclerosis and methods for their correction. - M .: 2008. - 64 p.)

However, in addition to the beneficial effects, statins can cause adverse reactions such as rhabdomyolysis. Rhabdomyolysis is the most severe and rare complication due to lysis of striated muscle cells and is accompanied by a decrease in circulating blood volume, a decrease in renal blood flow, acute renal failure, and shock. When myocytes are damaged, the iron pigment myoglobin enters the bloodstream, which, entering the kidneys, clogs the renal tubules, causing acute tubular necrosis and renal failure. With rhabdomyolysis, pain is observed in the calf muscles, lumbar region or throughout the body, there is a sharp weakness, fever, nausea, vomiting, urine color changes (red or brown).

In addition to rhabdomyolysis, other side reactions can be observed: myositis (especially in patients with high body temperature), increased activity of liver enzymes, skin rash, insomnia, peripheral neuropathy, allergic reactions (lupus-like symptoms that occur when using the drug for more than 6 months). There is evidence of the danger of a sharp cessation of statins in patients with acute atherothrombosis (cerebral stroke, acute coronary syndrome). According to the results of published studies, this leads to excessive activation of the heterodimeric O-proteins Kyo and Kae, as a result of which the production of active oxygen compounds is enhanced, the bioavailability of nitric oxide is reduced, inflammatory reactions are activated, and the risk of thrombosis is increased. In patients with acute coronary syndrome, a sudden cessation of receiving 1,025,844 ma statins significantly increases the risk of death and the development of thrombotic complications, while in patients with stable angina pectoris, discontinuation of these drugs is not accompanied by an increased risk of adverse events. In patients with acute ischemic stroke, a sudden cessation of statins is associated with a higher risk of developing early neurological complications and an unfavorable prognosis. It should be noted that statins are contraindicated in active liver diseases, increased activity of hepatic transaminases (3 or more times normal), alcoholic liver damage, cirrhosis of the liver, and skeletal muscle diseases.

In the patent of the Russian Federation No. 2388479 it is indicated that all hypocholesterolemic drugs are expensive agents with a number of side effects, of which hepatotoxicity comes first. With mono- and combination therapy with HMG-CoA reductase inhibitors, cases of increased activity of alanine and aspartic transaminases (which is a biochemical indicator of the cytolytic syndrome) with the development of hepatomegaly with steatosis are described. Hepatotoxicity is also recorded with the use of ezetimibe. There are reports of severe rhabdomyolysis with the use of HMG-CoA reductase inhibitors. In a large number of cases, the described undesirable effects are dose-dependent, at the same time, an increase in the dose of the drug is dictated by the insufficient effectiveness of previous dosages. The combined use of statins and ezetimibe potentiates the side effects of drugs, especially hepatotoxicity. To address these shortcomings, a method for the correction of hypercholesterolemia by taking 1 ml of sporobacterin probiotic 2 times a day for 30 days is proposed.

Biologically active additives (BAA) are known, which include selenium compounds. The selenium contained in them promotes the metabolism of fats and cholesterol, preventing the formation of atherosclerotic plaques, reducing the likelihood of occurrence or progression of coronary heart disease. Selenium prevents agglutination of blood cells and, acting on the vascular endothelium, prevents the development of hypertension. Selenium is involved in the synthesis of coenzymes that affect the recovery of the heart muscle after myocardial infarction, acts directly in the focus of necrosis, suppressing the process of damage to myocardiocytes.

These dietary supplements include:

Dietary supplement Vita-selenium containing 100% Jerusalem artichoke and selenium concentrate (1 tablet contains 50 micrograms of selenium) and manufactured by Rodnik Zdoroviya, Russian Federation (1 Шр: // \ у \ у \ у.го / пе1.ги / ргоб уба8е1еп1.рйр3 );

Selenovital ™ dietary supplement containing an organic mineral complex of yeast autolysate, selenium-containing spirulina, vitamins C, E, green tea extract and manufactured by Siberian Health Corporation, Russian Federation (Lair: //№№№.81 Lua1eo.sot/kaGa1od.ryt1? 1b = 1423);

Dietary supplement Vita-selenium E containing selenium in the form of the amino acid selenomethionine, i.e. the most accessible for the body, and vitamin E. The specified dietary supplement is produced by ChUP Radmedtech in conjunction with UP Ligur (Republic of Belarus), bd: //№№№.gabteFey.yu/2009-06-30-10-26-07/2009-06 -30-1028-14 / 2009-07-03-09-28-18 / 2009-07-03-09-44-46. Fri1.

According to TU RB 690032628.005-2002 (prototype) dietary supplement Vita-selenium E is intended for use in order to reduce the risk of cancer, cardiovascular diseases, enhance the protective functions of the body under environmentally unfavorable living conditions. The components of dietary supplements - the amino acid selenomethionine and vitamin E - are powerful antioxidants that control the process of lipid peroxidation, prevent the occurrence of a number of malignant tumors that contribute to the normal functioning of the cardiovascular system, eyes, pancreas, liver, delay the aging process, strengthen the immune system and increasing physical stamina.

Known dietary supplement Vita-selenium E has the following composition (per capsule), mg:

selenomethionine - from 0.05 to 0.20; vitamin E - from 10 to 40, and pharmaceutically acceptable additives: microcrystalline cellulose, ascorbic acid, magnesium stearate and methyl cellulose.

This dietary supplement is recommended for the prevention of cardiovascular diseases, to reduce the risk of cancer, for the prevention of viral diseases.

The use of dietary supplements Vita-selenium E for the prevention and correction of hypercholesterolemia is unknown.

The task of the invention is a new tool for the correction of hypercholesterolemia.

The problem is solved by the use of biologically active additives Vita-selenium E composition:

selenomethionine - 0.05-0.20 mg; Vitamin E - 10-40 mg, pharmaceutically acceptable additives in pharmaceutically acceptable amounts, as a means for the prevention and correction of hypercholesterolemia.

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Microcrystalline cellulose, ascorbic acid, magnesium stearate and methyl cellulose are used as pharmaceutically acceptable additives.

It was unexpectedly found that when using this dietary supplement in people with hypercholesterolemia, a decrease in serum cholesterol level of 37.5% is observed against the background of a tendency to normalize the ratio of concentrations of low density lipoproteins (LDL) and high density lipoproteins (HDL).

The inventive composition is prepared as follows. Microcrystalline cellulose, selenomethionine, vitamin E, ascorbic acid, methyl cellulose and magnesium stearate are weighed in the quantities necessary to produce a given number of capsules according to the recipe. The specified raw materials are placed in a mixer and mixed until a homogeneous mass is formed. The resulting homogeneous mixture is packaged using a capsulator into gelatin capsules.

The following is a specific example of the application of the well-known dietary supplement Vita-selenium E for a new purpose, not limiting the scope of claims.

Example.

The determination of serum levels of total cholesterol, HDL and β-lipoproteins was performed on a B8-200 biochemical analyzer (South Korea).

The results of clinical trials of dietary supplements Vita-selenium E are presented in the table.

A patient, No. p / p Age Total cholesterol Duration course treatment Before treatment After course Patient 1 (female) 40 years 5.1 4.6 14 days Patient 2 (female) 55 years 8 5 14 days Patient 3 (male) 58 years 7.2 6.4 14 days HDL 0.99 HDL 2.46 7 days LDL 4.3 LDL 2.24 Patient 4 (male) 71 years 5.7 5.2 10 days Patient 5 (male) 39 years 6.2 5,0 14 days Patient 6 (male) 64 years 6 5.7 3 days Patient 7 (male) 38 years 6.5 4.9 14 days HDL 0.9 1.9 LDL 3.9 2.2

The obtained experimental data confirm that the use of dietary supplements Vita-selenium E helps to reduce the total level of cholesterol in blood plasma, helps to reduce the level of low density lipoproteins (LDL) and at the same time increases the level of high density lipoproteins (HDL) in blood plasma.

Claims (1)

The use of a biologically active additive containing 0.05 mg of selenomethionine, 10 mg of vitamin E and pharmaceutically active additives, namely microcrystalline cellulose, ascorbic acid, magnesium stearate and methyl cellulose, in pharmaceutically acceptable amounts as a means for the correction of hypercholesterolemia.