Infusion solution for the treatment of diseases of the cardiovascular system

 

(57) Abstract:

The invention relates to medicine, namely to create a means for the treatment of cardiovascular diseases. Infusion solution contains, by weight. %: taurine - 5,500-11,000; potassium Asparaginate - 0,997-1,244; magnesium Asparaginate - 0,701-0,873; sorbitol - 1,000-5,000, and water for injection to 100%. The technical result is the achievement of a higher level and a wide range of specific activity, while reducing or eliminating side effects. 3 table.

The invention relates to medicine and pharmaceutical industry, in particular to the creation, production and application of funds for the treatment of cardiovascular diseases.

Known drug "Strophanthin", which is used in acute cardiovascular insufficiency, severe forms of chronic circulatory failure II and III in the cardiac decompensation with a normal heart rate or predicitions form of atrial fibrillation. Assign strophanthin intravenously or intramuscularly. Contraindicated strophanthin when sudden changes of organic heart and blood vessels, acute myocarditis, endocarditis, deep cardiokine nausea and vomiting (1).

Known drug "Digoxin", which is used for chronic circulatory failure I-II a and II B of degree at tahiaritmijami form of atrial fibrillation, paroxysmal atrial fibrillation, paroxysmal supraventricular tachycardia, circulatory failure in patients with myocardial infarction. Prescribe digoxin into tablets, drops or intravenously. The use of digoxin requires care in acute coronary insufficiency, active myocarditis, severe bradycardia, etc. In case of overdosing digoxin may experience slow conduction of the heart bigeminiya, nausea, vomiting, loss of appetite and other side effects (2).

Known drug "Clanid", which is used in the acute and chronic circulatory failure II and III degree, tahisistoliceskih form of atrial fibrillation, supraventricular form of paroxysmal tachycardia. Assign Zeland into tablets, drops or intravenously. Contraindications to use of Zelanda the same as digoxin (3).

Known drug "Asparkam" in the form of solution for injection, which consists of potassium asparagi the TMA, associated with intoxication by drugs digitalis, with paroxysmal atrial fibrillation, in the treatment of coronary insufficiency, and hypokalemia, which is caused by the use salureticheskoe funds. Contraindicated drugs in acute and chronic kidney insufficiency and hyperkaliemia. Possible side effects as nausea, dizziness (4).

Known drug containing taurine, lactose and hydroxypropylcellulose in the ratio of 1000: 275: 25. The tool is intended for treatment of heart failure (5).

It is known for the treatment of neurological disorders and migraine, containing taurine, calcipotriol, glycine, L-leucine, L-carnitine, pyridoxalphosphate, gluconate (6).

Known drug "Panangin" in the form of solution for injection, which consists of potassium Asparaginate, magnesium Asparaginate, sorbitol and water for injection. The drug is used with hypokalemia, as supportive therapy for angina, myocardial infarction, heart failure, heart rhythm disturbances, including those caused by an overdose of the drug digitalis. Panangin is contraindicated in acute and chronic renal failure, the ISU is area, violations of the conductance of myocardium. When intravenously possible paradoxical reaction in the form of increase in the number of Electrostal, and with rapid intravenous possible effects of hyperpotassemia and hypermagnesemia (7).

Closest to the claimed is the drug "Asparaginate potassium and magnesium" (Berlin Chemie, Germany) in the form of solution for infusion, which consists of potassium and magnesium asparaginates (the original substance is potassium hydroxide, magnesium oxide, DL-aspartic acid), and sorbitol (sorbitol) and water for injection. The drug is used with hypokalemia, as supportive therapy for angina, myocardial infarction, heart failure, heart rhythm disorders, including those caused by peredozirovka the drug digitalis. The drug is contraindicated in acute and chronic renal failure, hyperkaliemia, hypermagnesemia, AB blockade, severe myasthenia gravis. Possible side effects as nausea, vomiting, diarrhea, disorders of the conductance of myocardium (8).

For reasons which interfere in the prototype the technical result achieved in the inventive tool, you should include the fact that qualitative and quantitative composition of its Alicia side effects and contraindications.

The basis of the invention the goal is to create tools for the treatment of cardiovascular diseases by such selection of the qualitative and quantitative composition of the components, which would ensure a higher level and a wide range of specific activity, reduced or eliminated the presence of side effects and contraindications, expanded range of indications.

The problem is solved in that the infusion solution for the treatment of cardiovascular diseases, containing potassium Asparaginate, magnesium Asparaginate, sorbitol, and water for injection, in accordance with the invention additionally contains taurine in the following ratio, wt. %:

Taurine - 5,500-11,000

Potassium Asparaginate - 0,997-1,244

Magnesium Asparaginate - 0,701-0,873

Sorbitol - 1,000-5,000

Water for injection - Rest

The technical result, which is obtained by carrying out the invention, is to achieve a higher level and a wide range of specific activity, while reducing or eliminating side effects and contraindications, expanding the range of indications.

The inventive tool "Turicum" can be used to treat patients with narusheniami.sleduet, ischemic heart disease, arterial hypertension, hypokalemia and other diseases of the cardiovascular system, as well as in the treatment of several diseases of the Central nervous system, infectious diseases.

Cited specific examples of carrying out the invention.

Example 1. Charged to the reactor water injection, heat it up to 70oC, then load the calculated amount of DL - aspartic acid and magnesium oxide, mix, add potassium hydroxide, again stirred to dissolve the components, after which add the sorbitol. The resulting solution was heated to 100oC, incubated for 15 min, then cooled to 65-75oC and load at mixing taurine. The resulting solution is cooled, bring water for injection up to the required volume, stirred, filtered and ampoliros. In the process of preparation of a solution is a reaction formation of dissociated in water of potassium and magnesium salts of DL-aspartic acid.

The inventive tool is the ratio of components, wt. %:

Taurine - 5,500

Potassium Asparaginate - 1,244

Magnesium Asparaginate - 1,701

Sorbitol - 1,000

Water for injection - Rest

Example 2. Asparaginovoi acid and magnesium oxide, mix, add potassium hydroxide, again stirred to dissolve the components, after which add the sorbitol. The resulting solution was heated to 100oC, incubated for 15 min, then cooled to 65-75oC and load at mixing taurine. The resulting solution is cooled, bring water for injection up to the required volume, stirred, filtered and ampoliros. In the process of preparation of a solution is a reaction formation of dissociated in water of potassium and magnesium salts of DL-aspartic acid.

The inventive tool is the ratio of components, wt. %:

Taurine - 7,000

Potassium Asparaginate - 1,120

Magnesium Asparaginate - of 0.786

Sorbitol - 2,000

Water for injection - Rest

Example 3. Charged to the reactor water injection, heat it up to 70oC, then load the calculated amount of DL-aspartic acid and magnesium oxide, mix, add potassium hydroxide, again stirred to dissolve the components, after which add the sorbitol. The resulting solution was heated to 100oC, incubated for 15 min, then cooled to 65-75oC and load at mixing taurine. The resulting solution was cooled, adjusted vora reaction occurs education dissociated in water potassium and magnesium help DL-aspartic acid.

The inventive tool is the ratio of components, wt. %:

Taurine - 11,000

Potassium Asparaginate - 0,997

Magnesium Asparaginate - 0,873

Sorbitol - 5,000

Water for injection - Rasht

Qualitative and quantitative composition the proposed drug "Turicum" completely solves the invention the task of creating a highly effective tool for the treatment of cardiovascular diseases.

Potassium Asparaginate (potassium salt of aspartic acid) is a supplier of potassium, essential for the functioning of the human body. Potassium is the main intracellular ion content in the serum of human blood is about 5,11 mmol/l potassium Ions play a significant role in regulating body functions, and modify its contents, as well as the relationship between intra - and extracellular fractions are accompanied by significant violations of the functional state of the organism. Thus, the increase in the concentration of potassium in the blood 4 times (which is possible only when administered intravenously) leads to cardiac arrest. The decrease in the concentration of potassium in the serum increases the risk of arrhythmia development in the application of large doses of digitalis. Content tabaci mechanism of processes of excitation and inhibition. The decrease in the potassium content is accompanied by the accumulation of sodium, which leads to a reduction in the functional capacity of cells in the body.

The presence of potassium in the inventive tool in the form of a salt of aspartic acid significantly increases the efficiency performance of the main functions of this element: potassium salts are easily absorbed in internal reception, rapidly excreted by the kidneys, are easily dissolved in water, have no local irritating action. Potassium Asparaginate increases the concentration of potassium in the tissues under conditions of potassium deficiency, shows antiarrhythmic, anticonvulsant activity, antioxidant and membrane-stabilizing effect, enhances biliary excretion and diuresis, increases the activity of liver microsomal enzymes, reduces symptoms of intoxication as a result of taking a number of drugs (cardiac glycosides, neurotropic, and others ).

The quantitative content of potassium Asparaginate due to the content of the components necessary for a successful reaction of the salt of aspartic acid. In addition, the content of potassium Asparaginate is dose-dependent: when the decline is not fully manifested necessary writercolumbia, toxicity due to accumulation in plasma and other

Magnesium Asparaginate (magnesium salt of aspartic acid) is a supplier of magnesium, necessary for the normal functioning of the human body. Thus, magnesium deficiency contributes to the development of atherosclerosis, platelet aggregation, leads to the deposition of lipids in the artery wall, fibrinous necrosis, chronic inflammation, media, adventitia coronary arteries and other

Drugs magnesium (chloride, sulfate) are widely used in the treatment of cardiovascular diseases. Study the relationship of metabolism of magnesium and potassium, as well as the role of these ions in the mechanism of excitation and contraction of the myocardium proved the feasibility of application of combinations of ions for the treatment of cardiovascular diseases in the form of salts of acids, such as asparaginates potassium and magnesium (Panangin, asparkam).

The quantitative content of magnesium Asparaginate due to the content of the components necessary for the successful formation of the magnesium salt of aspartic acid. In addition, the content of magnesium is dose-dependent and if the decline is not fully manifested the level of the specific aminoethanesulfonic acid) - chemically stable natural compound that is contained in almost all biological systems and in the living organism has the ability to stabilize cell membranes, increase the structural resistance of the cells to stimulate cell division, without showing any toxic effect. Such properties of taurine cause a wide spectrum of physiological activity, such as effects on the cardiovascular system, Central nervous system, carbohydrate metabolism, liver function, retina, cholesterol metabolism, radioprotective effect on behavioral responses, etc. for Example, research has shown that an antiarrhythmic effect of taurine is associated with the prevention of loss of potassium infarction. Revealed enhanced immobilization of calcium by mitochondria in the presence of taurine. In addition, taurine exerts a tonic and restorative effect. An important factor is that taurine has a very low toxicity. But there are some disadvantages which are inherent in the taurine: poor penetration through hematoencephalic barrier (only 1% of taurine, which was injected intravenously, can be identified in the tissues of the brain), as well as the complexity of the software in the target organ of the local contesta (combination of taurine with asparaginates potassium and magnesium) and its application in the form of an infusion solution, achieve maximum therapeutic effect of all active components, in particular taurine utilized damaged tissue of the heart, and not eliminated in the urine. This prevents the disturbance of cellular metabolism and cell death in the myocardium.

The quantitative content of taurine in the claimed means of factors: when the amount of taurine is less than the claimed value is not achieved the appropriate level of specific activity. The dose of taurine more proposed values does not produce a tangible increase in its specific effect, moreover, lead to problems of a technological nature: the solution destabiliziruetsya due to crystallization of taurine.

As in the prototype part of the proposed drug introduced sorbitol, which acts as a stabilizer of injection solution. Studies have confirmed that in a number of stabilizers, which included sorbitol), polyethylene glycol and propylene glycol, the most acceptable is the sorbitol in amounts of 1-5%. The introduction of this stabilizer is allowed to obtain the infusion solution with a lifespan of up to two years. In the quantitative content of sorbitol is less than the claimed value is not performed its function of stabilizer and co-solvent. Use tsya its stabilizer function.

Conducted preclinical studies indicate the advantages of the proposed drug before means of comparison, solutions of asparaginates potassium and magnesium (prototype), solutions of taurine in various concentrations. Were used such model experiments: potassium chloride pathology of heart rhythm disorder and cardiac function, digitaline intoxication, izadrin-pitufina myocardial ischemia. In tables 1, 2, 3 summarizes the results of these studies.

The research results presented in table 1 show that in control experiments under the influence of intravenous calcium chloride is 100% death of animals, which is caused by cardiac activity: a decrease in R-wave, arrhythmia, with the further disappearance of teeth, P, G, S. the life Expectancy of control animals with pathology is (50,5 6,3) C. Under the influence means the prototype lifespan of experimental animals compared to control increased in 3-14 times. However, changes in electrocardiographic indices close to the norm, not detected (0). Study of the effect of a solution of taurine on similar indicators show that the duration gatechecked changes close to normal was observed in only two experiments of six and amounted to 20-30 C. Under the influence of the proposed drug duration of pathological phenomena in electrocardiographic indices decreased 1.6 times in comparison with control and 3.5-7 times - with the means of comparison. Life expectancy in comparison with control increased 25 times, in comparison with the tool prototype - 1.8-8 times.

The results presented in table 2 indicate significant benefits of the proposed drug before means of comparison when removing the effects of toxic effects of digoxin.

The research results presented in table 3, indicate that under the influence of the tool prototype has killed 50% of the test in comparison with control (100%). A solution of taurine almost did not show a therapeutic action on this model (11% of animals without pathology). The inventive tool 100% prevents the death of experimental animals and 90% of restores changes in electrocardiographic parameters, which is 3.2 times higher in comparison with the tool prototype.

Clinical studies have confirmed the high efficacy of the proposed drug for the treatment of myocardial infarction and its oloracolozel large doses of taurine in the area of the affected organ. The most effectively manifested antiarrhythmic action of active ingredients, reduced anginal pain and paroxysmal form of atrial fibrillation, decreased heart rate, liquidated ventricular premature beats, enhances the metabolic processes in the body, etc.

Statistical studies indicate that cardiovascular pathology at the present stage not only does not lose its "advanced" positions in the overall morbidity of the population, but also characterized by a clear tendency to increase and "rejuvenation". This is a more acute effect on the health needs in drugs for the treatment of diseases of the cardiovascular system. Long experience in the treatment of these diseases indicates the necessity of providing benefits combined funds, the components of which are actively working on various stages of pathogenesis of a particular disease. Therefore, the development and production of these means is the actual task of medicine and pharmaceutical industry.

Thus, in the present invention is entirely the task of creating a highly effective tool for the treatment of cardiovascular the Moscow M. D. Drugs. M , "Medicine", 1977. T. 1, S. 357.

2. Mashkovsky M. D. Medicines. M , "Medicine", 1977. T. 1, S. 349.

3. Mashkovsky M. D. Medicines. M , "Medicine", 1977. T. 2, S. 351.

4. Patent of Ukraine N 14462, class a 61 K 31/195. Publ. bull. "Promyslova Vlasnist", 1997, N 2, S. 3.1.48.

5. Lined with Japan's bid N 58-140017.

6. The application of EPO N 0288447.

7. Drugs foreign companies in Russia: a Handbook. - Moscow: Attraversare, 1993. - S. 176-177.

8. Drugs foreign companies in Russia: a Handbook. - Moscow: Attraversare, 1993. - S. 176 (prototype).

Infusion solution for the treatment of diseases of the cardiovascular system, containing potassium Asparaginate, magnesium Asparaginate, sorbitol, and water for injection, characterized in that it further contains taurine in the following ratio, wt. %:

Taurine - 5,500-11,000

Potassium Asparaginate - 0,997-1,244

Magnesium Asparaginate - 0,701-0,873

Sorbitol - 1,000-5,000

Water for injection - Rest

 

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