Essential fatty acids for prevention and/or treatment of depression in patients suffering from coronary heart disease or coronary artery disease

FIELD: medicine.

SUBSTANCE: treatment of depression in the patients suffering from coronary heart disease is ensured by introduction of essential fatty acids or a related drug containing eicosanpentanoic acid ether or docosahexaenoic acid ether, either separately, or mixed in the developed effective doses.

EFFECT: improved cardioprotective and antidepressive action in the given group of patients.

45 cl

 

The technical FIELD TO WHICH the INVENTION RELATES.

Essential fatty acids and containing compositions intended for the prevention and/or treatment of depression in patients with cardiovascular disease such as coronary heart disease and/or coronary artery disease or disease of the blood vessels.

The LEVEL of TECHNOLOGY

In one embodiment, the present invention relates to the use of pharmaceutical compositions containing ethyl esters of fatty acids derived from fish oil, preferably having a high content of the mixture of ethyl esters (20:5ω-3) eicosapentaenoic acid (EPA) and (22:6ω-3) docosahexanoic acid (DHA), for the prevention and/or treatment of depression in patients with coronary artery disease.

It is well known that some essential fatty acids contained in fish oil, have a curative effect, providing for the prevention and treatment of cardiovascular disorders, such as treatment of hypertension, thrombosis, hypercholesterolemia, arteriosclerosis, heart attack, brain, prevention of sudden death in patients after myocardial infarction, improved endothelial function and prevention and treatment of hyperlipidemia.

As examples can be mentioned U.S. patents US 5502077, US 5656667 and US 5698594. Before the prevention of cardiovascular events, particularly lethal outcome in patients after stage hospitalization for acute myocardial infarction (AMI) described in the application for international patent WO 00/48592.

In the prior art, in particular, there is evidence of the applicability of fatty acids belonging to the group of ω-3, more preferably (20:5ω-3) eicosapentaenoic acid (EPA) and (22:6ω-3) docosahexanoic acid (DHA)for the treatment of the above disorders.

Fatty acid EPA, which is the predecessor PGI3 and The, provides warning of platelet aggregation effect and antithrombotic effects, which can be attributed to the inhibition of cyclooxygenase (similar to the influence of aspirin) and/or competition with arachidonic acid with respect to this enzyme, with a consequent reduction in the number of synthesized PGE2 and The, which are known agents causing platelet aggregation.

On the other hand, fatty acid DHA is the most important component of brain lipids in humans and, in addition, being a structural component of platelets directly hinders improvement of the fluidity of platelets and therefore plays an important role in antithrombotic effect.

In the application for international patent WO 89/11521, the description of which is included in the present invention as a reference, often the spine, described the industrial extraction of mixtures with a high content of polyunsaturated acids, including EPA and DHA and their ethyl esters from animal and/or vegetable oils.

Reported that mixtures of fatty acids, particularly EPA/DHA obtained according to WO 89/11521 are especially useful for treatment of cardiovascular diseases.

However, it was shown that used currently in medicine methods of treatment are ineffective for patients with coronary artery disease.

SUMMARY of INVENTION

In one embodiment, the present invention relates to the use of pharmaceutical compositions containing ethyl esters of fatty acids derived from fish oil, preferably having a high concentration mixture of ethyl esters (20:5ω-3) eicosapentaenoic acid (EPA) and (22:6ω-3) docosahexanoic acid (DHA), for the prevention and/or treatment of depression in patients with cardiovascular disease such as coronary heart disease, coronary artery disease or disease of the blood vessels.

In one embodiment, the present invention relates to a new method of prevention and/or treatment of depression in patients with cardiovascular disease. In another embodiment, patients, Strada is related coronary heart disease and/or coronary artery or vascular disease. In yet another embodiment, the cardiovascular disease is coronary artery disease or disease of the blood vessels. The method proposed in the present invention, includes an introduction to the specified patient an effective amount of a medicinal product containing essential fatty acids with a high content of ethyl ether eicosapentanoic acid (EPA), ethyl ether of docosahexanoic acid (DHA) or a high content of a mixture of ethyl ether eicosapentanoic acid (EPA) and ethyl ether of docosahexanoic acid (DHA). In one embodiment, is contained in a large amount of the mixture is contained in a large amount of a mixture of ethyl ether eicosapentanoic acid (EPA) and ethyl ether of docosahexanoic acid (DHA).

The high content of the ethyl ester of EPA or ethyl ester of DHA or a large content of the mixture should be understood as a content of not less than 20 wt.% EPA or DHA or at least 20 wt.% a mixture of EPA and DHA.

In one embodiment, the present invention relates to the use of essential fatty acids, which are a mixture of ethyl ether eicosapentanoic acid (EPA) and ethyl ether of docosahexanoic acid (DHA), for the prevention and/or treatment of depression in patients who serdechno-vascular disease, in one example, in patients suffering from coronary heart disease and/or coronary artery or vascular disease, in which the content of EPA and DHA in such a mixture is more than 25 wt.%.

In another embodiment, the present invention relates to the use of therapeutically effective amounts of essential fatty acids with a high content of EPA, DHA or a mixture thereof, for preparing a medicinal product intended for the treatment of cardiovascular diseases such as coronary heart disease and/or coronary artery disease or disease of the blood vessels.

Other features and advantages of the present invention will be understood from the subsequent detailed description. However, it should be understood that the detailed description and specific examples, if they indicate the preferred embodiments of the present invention are illustrative only, as for specialists in the art from this detailed description should be apparent, various changes and modifications are included in the nature and scope of the present invention.

A DETAILED DESCRIPTION of the PREFERRED OPTION IMPLEMENTATION

When used in the present invention, the terms "includes" and "including" are used interchangeably, and not mutually exclusive.

Long is on the identification of new risk factors for coronary artery which includes depression. Great depressive disorders, and symptoms of depression was associated with high incidence of cardiovascular disease and mortality from cardiovascular disease. In addition, after the occurrence of coronary heart disease increases the risk of heart attack fatalities. Severe ventricular arrhythmia leading to sudden rupture of the heart, apparently, are the leading cause of death in patients suffering from depression. In addition, it was shown that patients suffering from anxiety and depressive disorders, reduced variability in heart rate. This fact can have great predictive value, because of the low variability in heart rate is a reliable predictor of sudden cardiac rupture. There is strong evidence that major depression is associated with changes in the status of omega-3 acids. It has been found that major depression significantly reduced the content of omega-3 fatty acids in erythrocyte membranes. In another study reported an inverse correlation and content of omega-3 fatty acids in erythrocyte membranes, and receipt of these polyunsaturated fatty acids from food with the severity of depression. It is known that the completion of the diet is to help EPA and DHA increases the content of these unsaturated fatty acids in erythrocyte membranes. Studies of patients after myocardial infarction showed that the completion of the diet with DHA and EPA increases the variability of the heart rate.

However, there is currently no safe and effective tools, for which it would be known that they warn depression in patients suffering from cardiovascular disease, and it is unlikely there are other means of treating depression in patients with cardiovascular disease. One study of the drug sertraline discovered its beneficial effect on patients after myocardial infarction with concomitant depression. It is well known that for patients suffering from cardiovascular diseases and depression, there is a greatly increased risk of cardiovascular disorders and death.

So still need better and effective prevention and/or treatment with drugs, in particular to prevent these relapses in patients with cardiovascular disease, and depression, and effective treatment of depression in these patients. Therefore, in one embodiment, the present invention relates to such an improved and effective prevention (the prevention and/or treatment of these patients with effective lekarstvennayaforma, in particular to prevent the above recurrence in patients with cardiovascular disease, and depression, and/or treatment of depression in these patients.

In one embodiment, the present invention relates to a new method of prevention and/or treatment of depression in patients with cardiovascular disease. In one embodiment, the cardiovascular disease is coronary heart disease and/or coronary artery disease or disease of the blood vessels. In another embodiment, the cardiovascular disease is coronary artery disease or disease of the blood vessels. In one embodiment, the method includes the introduction of a specified patient an effective amount of a medicinal product containing essential fatty acids with a high content of ethyl ether eicosapentanoic acid (EPA), ethyl ether of docosahexanoic acid (DHA) or a high content of a mixture of ethyl ether eicosapentanoic acid (EPA) and ethyl ether of docosahexanoic acid (DHA). In one embodiment, introduces a tool that has a high content of a mixture of ethyl ether eicosapentanoic acid (EPA) and ethyl ether of docosahexanoic acid (DHA). The present invention also relates to applied the Yu essential fatty acids, such as EPA, DHA or a mixture thereof, for the prevention and treatment of depression in patients with cardiovascular disease.

For ease of description, the terms "ethyl ester of EPA and ethyl ester of DHA in the present invention will also be referred to as "EPA", "DHA". The high content of the ethyl ester of EPA or ethyl ester of DHA or a large content of the mixture should be understood as a content of not less than 20 wt.% EPA or DHA or at least 20 wt.% a mixture of EPA and DHA.

In particular, the present invention relates to the use of essential fatty acids, containing a mixture of ethyl ether eicosapentanoic acid (EPA) and ethyl ether of docosahexanoic acid (DHA) for the prevention and/or treatment of depression in patients with cardiovascular disease, preferably in patients suffering from coronary heart disease and/or coronary artery or vascular disease, wherein the content of EPA and DHA in such a mixture is more than 25 wt.%.

In one embodiment, essential fatty acid, which has a high content of EPA or DHA proposed in the present invention preferably contains more than 25 wt.%, more preferably from about 60 to about 100 percent of such air. These compounds can be obtained by known methods.

essential fatty acids, having great content is a mixture of EPA and DHA, preferably, this mixture had a content of EPA and DHA, greater than 25 wt.%, preferably from about 30 to about 100 wt.%, more preferably about 85 wt.%. To a mixture of EPA/DHA preferably, EPA contained in the amount of about 40 to 60 wt.%, and preferably with DHA contained in an amount constituting from about 25 to about 45-50%. In any case, the preferred mass ratio of EPA/DHA in the mixture of EPA/DHA ranges from about 0.9 to 1.5.

PHARMACOLOGY

Cardiovascular diseases are the leading cause of morbidity and disability in the United States, where an estimated 6 million people suffer from symptomatic coronary heart disease. Major depression occurs at earlier age and with greater frequency than previously. Changes in the content of phospholipids and cholesterol, which are structural components of all cell membranes of the brain, can cause changes in microviscosity membranes and, consequently, changes in various neurotransmitter systems, which are associated with the pathophysiology of depression, for example, serotonin and (nor) adrenaline. Major depression and depressive symptoms, although usually found in infected people people often do not di is gestroud and not subjected to treatment in patients suffering from cardiovascular disease. In patients suffering from coronary heart disease, the prevalence of major depression is almost 20% and the prevalence of minor depression is approximately 27%. Depression (major depressive disorders and depressive symptoms) associated with the incidence of cardiovascular diseases. For patients suffering from depression, the forecast after the occurrence of coronary heart disease worse than for patients not suffering from depression. Patients suffering from depression, worse comply with recommendations for reducing the risk for heart during recovery after myocardial infarction. When the great depression reduced the fractions of ω-3 esters of cholesterol and increased the ratio of C20:4 ω-6/C20:5 ω-3 esters of cholesterol and phospholipids.

Depression is an important independent predictor of fatal outcome after surgery for coronary artery. Survival analysis taking into account age, sex, number of grafts, presence of diabetes, Smoking, ejection fraction of the left ventricle and the presence of previous myocardial infarction shows that for patients with depression from mild to severe after surgery (adjusted risk ratio (PR) is equal to 2.4, p=0.001) and depression from weak d is moderate, persisting for up to 6 months after surgery (adjusted PR 2,2), the mortality rates are higher than for those with no depression. In addition, with reduced survival associated symptoms of depression from mild to moderate in patients after acute myocardial infarction. The highest mortality was observed in patients who have manifested the most pronounced symptoms of depression. However, when compared with patients with no depression, higher mortality was also observed in those who appear very weak symptoms of depression, usually are not considered to be clinically significant. Increased mortality after myocardial infarction is observed in women and in men. In depressed women mortality within one year after heart disease is about 3 times higher, and depressed men is 2.5 times higher than in the absence of depression in women and men respectively. Preliminary studies have shown that in addition to the danger of death associated with depression after myocardial infarction, for depressed patients who have lived 1 year after myocardial infarction, increased costs of medical care associated with re-hospitalization, and outpatient treatment. Causes of increased mortality and morbidity is of patients suffering from coronary heart disease and depression are not fully understood. However, there is evidence that depression anomalies are observed in the absorption and metabolism of essential fatty acids in combination with a reduced formation of esters of cholesterol. There is a direct correlation between the ratio of arachidonic acid to the number eicosapentanoic acid in the blood with clinical symptoms of depression. Also found a significant inverse correlation between the content of EPA in red blood cells with the severity of depression. Changes in the content of phospholipids and cholesterol, which are structural components of all cell membranes of the brain, can cause changes in microviscosity membranes and consequently changes in various neurotransmitter systems such as serotonin and (nor) adrenaline. It is well known that these neurotransmitters play an important role in the pathophysiology of depression. Finally, a decrease in food intake and reduce body weight, concomitant severe depression can cause changes in the composition of fatty acids in phospholipids and esters of cholesterol in the serum, which in itself may affect the fluidity of membranes and inflammatory response.

The effectiveness of the treatment in the context of the present invention is confirmed by indirect preclinical and clinical the data.

1. Consumption of large quantities of fatty ω-3 acids is associated with a General reduction transmission signals associated with phosphatidylinositol, arachidonic acid and other systems.

2. DHA is involved in the metabolism of dopamine and serotonin in the growing rat brain.

3. Serotonergic and other neurochemical effects of fatty ω-3 acids that have been observed in animals, evidence of antidepressant activity.

4. Epidemiological data show that the observed in different countries, differences in the prevalence of major depression and bipolar disorders are directly related to the amount of consumed fish.

5. Epidemiological studies have demonstrated a correlation between fatty acid composition in plasma with depression in the elderly.

6. Bipolar violations in the pathophysiology plays the role of hyperactivity signaling cells.

7. Patients suffering from bouts of major depression, there is a significant decrease in the content of DHA and EPA in erythrocyte membranes.

8. Omega-3 fatty acids lead to stabilize the mood in major depression and other neuropsychiatric disorders.

9. The addition of EPA in the treatment of resistant depression associated with remission of symptoms, structural changes in the brain and weakening exchange Nar is the R phospholipids.

10. Omakor, highly concentrated blend of EPA and DHA, increases the amount of EPA and DHA in erythrocyte membranes.

The above data show that the present invention relates to new and useful therapeutic method for the prevention and/or treatment of depression in patients with cardiovascular disease, preferably in patients suffering from coronary heart disease and/or coronary artery or vascular disease. In accordance with this present invention relates to a method for prevention and treatment of depression in patients with coronary vessels, and preferably in patients suffering from coronary heart disease and/or coronary artery or vascular disease involving the introduction of such a patient a therapeutically effective amount of a medicinal product containing essential fatty acids with a high content of ethyl ester of EPA or ethyl ester of DHA or high content mixtures thereof.

Essential fatty acids are proposed in the present invention, may have a high content of, for example, comprising more than 25 wt.%, EPA or DHA or their mixtures. However, preferably the ethyl esters of EPA and DHA contained in the form of their mixture with the content of EPA and DHA in excess of 25 wt.%, before occhialino - from about 30 to about 100 wt.%, in one embodiment, is approximately 80, 81, 82, 83, 84% or, preferably, about 85 wt.%.

Based on the available data in the preferred embodiment of the present invention, the dose of essential fatty acids, containing a mixture of EPA and DHA in the amount of 85 wt.%, intended for oral administration to a patient may range from about 0.7 to about 6 g per day, preferably when she is about 1 g per day.

In one embodiment, the tool having a high content of EPA, DHA or a high content of their mixture, placed in a capsule such as a gelatin capsule, using technologies known in the art. In one embodiment, the gelatin capsule is a capsule containing 1000 mg. In another embodiment, the specified capsule comprises 90 wt.% ethyl esters of omega-3 fatty acids. In another embodiment of the above 90 wt.% in a capsule, containing 1000 mg, about 465 mg EPA is and about 375 mg is DHA. In yet another embodiment, the specified capsule contains 1000 mg includes approximately 4 mg of α-tocopherol in a suitable carrier (such as partially hydrogenated vegetable oils, including soybean oil) and other ingredients gelatin capsules,such as gelatin, glycerin and purified water. In one embodiment of the present invention injected dose is 4 grams per day in capsules containing 1000 mg.

To provide the necessary content in the blood is the amount of drug in the form of a mixture of EPA and DHA (or number EPA or only DHA) can be entered during the day in several divided doses or, preferably, as a single dose. Obviously, the amount of preparation determined by the attending physician in accordance with age, weight and General condition of the patient. As such, a "therapeutically effective amount" is an amount which when used dosages and periods of time necessary to achieve the desired therapeutic result. It should be understood that this number may vary depending on such factors as the type of pathological condition, age, sex and weight of the individual, and the ability of a substance to cause the individual the necessary reaction.

Drug, for example, in the form of a pharmaceutical composition proposed in the present invention can be prepared using technologies known in the art. The preferred route of administration is oral, however, possible alternative routes of administration, such as parenteral, and the decision is made by the doctor. Generic what this means or pharmaceutical composition may contain the required amount of substance, for example, to have a high content of EPA, DHA or high content mixtures thereof proposed in the present invention, and include the pharmaceutically acceptable solvent, for example, carriers, inert fillers, excipients and buffers, for example, substances used in pharmaceutical preparations or known in the art, for example described in the publication Remington''s Pharmaceutical Sciences (Alfonso R. Gennaro ed. 18thedition 1990).

Embodiments of the present invention are further defined in the dependent claims.

The following examples illustrate the preparations suitable for oral administration, but in no way limit the present invention.

Gelatin capsules

In accordance with known pharmaceutical technologies were preparing capsules having the following composition and containing 1 g of the active ingredient (EPA and DHA, the content of 85%) in each capsule.

The drug 1

EPA-ethyl ester525 mg/capsule
DHA-ethyl ester315 mg/capsule
d-alpha-tocopherol4 ME /capsule
gelatin 246 mg/capsule
glycerin118 mg/capsule
red iron oxideof 2.27 mg/capsule
yellow iron oxideof 1.27 mg/capsule

The product 2

Ethyl esters of polyunsaturated
fatty acids1000 mg

When the content of ethyl
esters of ω-3 polyunsaturated
acids (eicosapentaenoic EPA
docosahexanoic DGK)850 mg
d-1-α-tocopherol0.3 mg
the gelatin succinate233 mg
glycerin67 mg
p-oxybenzoic sodium1,09 mg
propyl-p-oxybenzoic sodium0,54 mg

Although the present invention is described with what is presently considered to be the preferred option done by the means, it should be understood that the present invention is not limited to those disclosed by the embodiment. On the contrary, the present invention includes various modifications and equivalent systems that are included in the nature and scope of the attached claims.

All publications, patents and patent applications in their entirety are included in the present invention by reference to the same extent as if it had been specified that each individual publication, patent or patent application in its entirety is included in the present invention by reference.

1. Method of prevention and/or treatment of depression in patients with cardiovascular disease, including the introduction of the indicated patient a therapeutically effective amount of a medicinal product containing essential fatty acids, which contains:
a) at least 20 wt.% ethyl ester eicosapentaenoic acid, or
b) at least 20 wt.% ethyl ether of docosahexanoic acid, or
C) at least 20 wt.% a mixture of ethyl ether eicosapentanoic acid and ethyl ester of docosahexanoic acid.

2. The method according to claim 1, wherein the cardiovascular disease is coronary heart disease and/or coronary artery disease or disease of the blood vessels.

3. The method according to claim 2, in which the cardiovascular for what yevanim is coronary artery disease or disease of the blood vessels.

4. The method according to any one of claims 1 to 3, in which the essential fatty acids contain at least 20 wt.% a mixture of ethyl ether eicosapentanoic acid and ethyl ester of docosahexanoic acid.

5. The method according to any one of claims 1 to 3, in which the essential fatty acids contain at least 20 wt.% ethyl ester eicosapentanoic acid or ethyl ester of docosahexanoic acid.

6. The method according to claim 4, in which the content of ethyl ether eicosapentanoic acid and ethyl ester of docosahexanoic acid in the mixture is from about 30 to about 85 wt.%.

7. The method according to claim 4, in which the drug is administered orally.

8. The method according to claim 1, in which the drug is administered orally.

9. The method according to claim 6, in which the drug is administered orally.

10. The method according to claim 7, in which the drug is administered orally in a dose comprising from about 0.7 to about 6 grams per day.

11. The method according to claim 8, in which the drug is administered orally in a dose comprising from about 0.7 to about 6 grams per day.

12. The method according to claim 9, in which the drug is administered orally in a dose comprising from about 0.7 to about 6 grams per day.

13. The method according to claim 10, in which the mass ratio of the ethyl ether eicosapentanoic acid/ethyl ether of dokusan is Aksenovo acid in a mixture of ethyl ether eicosapentanoic acid and ethyl ester of docosahexanoic acid is from about 0.9 to 1.5.

14. The method according to claim 11, in which the mass ratio of the ethyl ether eicosapentanoic acid/ethyl ether of docosahexanoic acid in a mixture of ethyl ether eicosapentanoic acid and ethyl ester of docosahexanoic acid is from about 0.9 to 1.5.

15. The method according to item 12, in which the mass ratio of the ethyl ether eicosapentanoic acid/ethyl ether of docosahexanoic acid in a mixture of ethyl ether eicosapentanoic acid and ethyl ester of docosahexanoic acid is from about 0.9 to 1.5.

16. The method according to claim 5, in which the content of ethyl ether eicosapentanoic acid or ethyl ester of docosahexanoic acid is approximately 60-100 wt.%.

17. The method according to claim 5, in which is contained ethyl ester eicosapentanoic acid or ethyl ester of docosahexanoic acid administered orally.

18. The method according to claim 5, in which is contained ethyl ester eicosapentanoic acid or ethyl ester of docosahexanoic acid administered orally.

19. The method according to clause 16, which contained ethyl ester eicosapentanoic acid or ethyl ester of docosahexanoic acid administered orally.

20. The use of a therapeutically effective amount of a medicinal product containing essential fatty acids, which contain at least 20 wt.% Adilov the th ether eicosapentanoic acid or at least 20 wt.% ethyl ether of docosahexanoic acid, or at least 20 wt.% a mixture of ethyl ether eicosapentanoic acid and ethyl ester of docosahexanoic acid and pharmaceutically acceptable solvent, for treatment of depression in patients with cardiovascular disease.

21. The application of claim 20, in which cardiovascular disease is coronary heart disease and/or coronary artery disease or disease of the blood vessels.

22. Use item 21, in which cardiovascular disease is coronary artery disease or disease of the blood vessels.

23. The use according to any one of p-22, in which the essential fatty acids contain at least 20 wt.% a mixture of ethyl ether eicosapentanoic acid and ethyl ester of docosahexanoic acid.

24. The use according to any one of p-22, in which the essential fatty acids contain at least 20 wt.% ethyl ester eicosapentanoic acid or ethyl ester of docosahexanoic acid.

25. The application of item 23, in which the content of ethyl ether eicosapentanoic acid and ethyl ester of docosahexanoic acid in the mixture is from about 30 to about 85 wt.%.

26. The application of item 23, in which the drug is administered orally.

27. Use A.25, in which the drug is administered orally.

28. Use p, inwhich the drug is administered orally at a dose component of from about 0.7 to about 6 grams per day.

29. The application of item 27, in which the drug is administered orally in a dose comprising from about 0.7 to about 6 grams per day.

30. Use p, in which the mass ratio of the ethyl ether eicosapentanoic acid/ethyl ether of docosahexanoic acid in a mixture of ethyl ether eicosapentanoic acid and ethyl ester of docosahexanoic acid is from about 0.9 to 1.5.

31. The application of clause 29, in which the mass ratio of the ethyl ether eicosapentanoic acid/ethyl ether of docosahexanoic acid in a mixture of ethyl ether eicosapentanoic acid and ethyl ester of docosahexanoic acid is from about 0.9 to 1.5.

32. The application of paragraph 24, in which the content of ethyl ether eicosapentanoic acid or ethyl ester of docosahexanoic acid is approximately 60-100 wt.%.

33. The application of paragraph 24, which contained ethyl ester eicosapentanoic acid or ethyl ester of docosahexanoic acid administered orally.

34. Use p, which contained ethyl ester eicosapentanoic acid or ethyl ester of docosahexanoic acid administered orally.

35. The use of essential fatty acids, containing at least 20 wt.% ethyl ester of amazement the OIC acid or at least 20 wt.% ethyl ether of docosahexanoic acid, or at least 20 wt.% a mixture of ethyl ether eicosapentanoic acid and ethyl ester of docosahexanoic acid, preferably use at least 20 wt.% a mixture of ethyl ether eicosapentanoic acid and ethyl ester of docosahexanoic acid, for the preparation of medicines used for the prevention and/or treatment of depression in patients with cardiovascular disease, preferably in patients suffering from coronary heart disease and/or coronary artery or vascular disease, more preferably in patients suffering from coronary artery disease or disease of the blood vessels.

36. Use p, in which the content of ethyl ether eicosapentanoic acid in ethyl ether of docosahexanoic acid or in a mixture of ethyl ether eicosapentanoic acid and ethyl ester of docosahexanoic acid, preferably the content in a mixture of ethyl ether eicosapentanoic acid and ethyl ester of docosahexanoic acid, is more than 25 wt.%.

37. Use p or 36, wherein the content of ethyl ether eicosapentanoic acid and ethyl ester of docosahexanoic acid in the mixture is from about 30 to about 100 wt.%.

38. Use p or 36, wherein the content of the ethyl ester e is codependancy acid and ethyl ester of docosahexanoic acid in a mixture of approximately 85%.

39. The use according to any one of p-38, in which the drug is intended for oral administration.

40. The application of § 38, in which the drug is intended for oral administration at a dose comprising from about 0.7 to about 6 grams per day.

41. Use p, wherein the ratio of ethyl ether eicosapentanoic acid/ethyl ether of docosahexanoic acid in a mixture of ethyl ether eicosapentanoic acid and ethyl ester of docosahexanoic acid is from about 0.9 to 1.5.

42. The use of essential fatty acids, containing ethyl ether eicosapentanoic acid or ethyl ester of docosahexanoic acid, for the preparation of medicines used for the prevention and/or treatment of depression in patients with cardiovascular disease, preferably in patients suffering from coronary heart disease and/or coronary artery or vascular disease, in which the content of ethyl ether eicosapentanoic acid or ethyl ester of docosahexanoic acid is more than 25 wt.%.

43. The application of § 42, at which the medicinal product is applicable for the prevention and/or treatment of depression in patients with coronary artery disease or disease of the blood vessels.

44. Application is by § 42 or 43, when the content of ethyl ether eicosapentanoic acid or ethyl ester of docosahexanoic acid is from about 60 to about 100 wt.%.

45. The use according to any one of p-44, in which the drug is intended for oral administration.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to a novel compound or its salt of formula 1: , where A, E, D, R0, R1-R4 and a assume values given in the formula of invention. The invention also relates to an antioxidant medicinal agent.

EFFECT: effectiveness during treatment of ischemic diseases of organs, during treatment of diseases caused by oxidation cell disorders and when inhibiting disorders of the retina.

4 cl, 1 tbl, 6 ex

FIELD: medicine.

SUBSTANCE: treating of lipidosis and body-weight reduction in the patients with cardiovascular diseases is ensured by diet therapy based on the lacto-vegetarian diet. It involves introduction of proteins in daily amount of 67-79 g, including animal 48-57%, fats in daily amount of 32-49 g, including animal 40-52%, carbohydrates in daily amount of 240-257 g, cholesterol in daily amount of 40-268 mg, cellulose in daily amount of 18-20 g, dietary fibers in daily amount of 150 mg, potassium (K) in daily amount of 4567-6433 mg, magnesium (Mg) in daily amount of 535-693 mg, vitamin E in daily amount of 44-53 mg, arginine in daily amount of 3.9-5.2 g, dehydrated powdered maral meat in daily amount of 1200 mg, microcrystalline cellulose in daily amount of 900 mg. Duration of the diet therapy course is 33 days.

EFFECT: method provides suppression of cholesterol biosynthesis and intensification of excretion thereof that reduces the atherogenic index, reduces manifestations of oxidative stress, with reduced risk of realisation of the modified factors of a cardiovascular pathology.

1 tbl

FIELD: medicine.

SUBSTANCE: as additional components, a new medicinal form contains stearic acid or its pharmaceutically acceptable salt, succinic acid or its pharmaceutically acceptable salt, microcrystalline cellulose, magnesium carbonate, starch and hydroxypropyl cellulose.

EFFECT: extended range of storage-stable preparations of 3-oxy-6-methyl-2-ethylpyridine as solid oral dosage forms without by-effects of existing preparations.

14 cl, 2 tbl

FIELD: medicine.

SUBSTANCE: invention concerns a solid oral dosage form composition containing therapeutically effective amount of aliskiren or its pharmaceutically acceptable salt in amount exceeding 46 wt %. The oral dosage form represents a tablet or a film-coated tablet. Aliskiren tablet is made by wet granulation with using mixed organic solvents or organic binding solutions.

EFFECT: elimination of aqueous granulation provides high stability of the dosage form of aliskiren and prolonged shelf-life.

18 cl, 2 ex

Antiishemic agent // 2384327

FIELD: medicine.

SUBSTANCE: there is offered to apply 4-(2-hydroxyethyl)phenol(n-thyrozol) as a medicinal agent with anti-ischemic properties.

EFFECT: intravenous introduction of n-thyrozol improves the survival rate of animals with old myocardial ischemia and reperfusion, reduces a region of myocardial ischemia, and enables higher integrity of myocardial tissue.

3 tbl, 3 ex

Triazole derivative // 2383536

FIELD: chemistry.

SUBSTANCE: described are novel triazole derivatives with general formula where values of radicals are given in the formula of invention, a pharmaceutical composition containing said derivatives, and a method of treating autoimmune diseases. Compounds with general formula (1) and their pharmaceutically acceptable salts have inhibition effect on S1P and its Edg-1 receptor (S1P1).

EFFECT: possibility of use as a pharmaceutical product.

43 cl, 10 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: for treatment of left ventricle hypertrophy (HLV) in patients with coronary disease in combination with hypertension during 6 months standard drug therapy, consisting of IATA, beta-blocker, aspirin and stanin is realised. Additionally ivabradin in day dose 5 - 15 mg is introduced in two intakes daily.

EFFECT: method ensures transformation of HLV in concentric remodeling of left ventricle and in such way reduces degree of cardiovascular complications risk.

2 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: pharmaceutical compositions include divalent, namely calcium, magnesium or zinc salt, of pravastatin or fluvastatin and omega-3 fat, for prevention, reduction or treatment of increased cholesterol levels, atherosclerosis, hyperlipidemia, cardio-vascular disorders and diseases, coronary heart disease and/or cerebrovascular disease.

EFFECT: improved bioavailability of compositions, easily obtained and introduced.

40 cl, 33 dwg, 2 tbl, 8 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to cardiology, and concerns treating of myocardial infarction (MI). That is ensured by primary transcutaneous transluminal coronary angioplasty with underlying standard conservative therapy is followed with myocardial unload with beta-blocker Carvedilol. Said myocardial unload is combined with introduction of Levosimendan at first administered as a bonus intravenously at 16 mcg/kg during 10 min, and then in stable AP it is infused intravenously within 20-38 hours in total dose 12.5 mg/kg at the rate 0.05 to 0.2 mcg/kg/minutes.

EFFECT: method provides higher survival rate and ensured clinical compensation in the MI patients of elderly and senile age with cardiac failure complications due to combination of endovascular revascularisation and myocardial unload with underlying introduction of inotropic stimulator Levosimendan in the developed doses and regimen.

2 tbl

FIELD: medicine.

SUBSTANCE: invention concerns medicine, neurology section and can find application in neurologic and neural rehabilitation clinic in treating the patients with aphasia. That is ensured by administration of acatinol memantin according to certain schedule with underlying logopedic lessons. Within the first week of therapy, the dose is 5 mg/day in the morning at mealtime. Within the second week, the dose is 10 mg/days, with 5 mg in the morning and in the evening. Within the third week, the dose is increased to 15 mg/days, with 10 mg in the morning and 5 mg in the evening. Within the fourth week, the dose is increased to 20 mg/days. And the maintenance dose makes 20 mg/days.

EFFECT: method provides effective treatment of apparent rough aphasia caused by disordered cerebral blood flow.

1 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel antagonists of serotonin 5-HT6 receptors - substituted 2-amino-3-sulfonyl-6,7,8,9-tetrahydro-pyrazolo[1,5-a]pyrido[3,4-e]pyrimidines of general formula 1 and substituted 2-amino-3-sulfonyl-5,6,7,8-tetrahydro-pyrazolo[1,5-a]pyrido[4,3-d]pyrimidines of general formula 2 or their pharmaceutically acceptable salts and/or hydrates, method of producing said compounds and pharmaceutical compositions, medicinal agents and treatment method. In compounds of formula 1 and general formula 2 , Ar is phenyl which is possibly substituted with halogen atoms, or a 6-member nitrogen-containing heteroaryl; R1 is a hydrogen atom, C1-C3alkyl which is possibly substituted with phenyl, C1-C5alkoxycarbonyl; R2 is a hydrogen atom, halogen or C1-C3alkyl; R13 and R23 are optionally identical substitutes selected from a hydrogen atom, optionally substituted C1-C3alkyl or R13 and R23 together with the nitrogen atom with which they are bonded form a nitrogen-containing 6-member saturated heteroaryl optionally substituted with C1-C5alkoxycarbonyl, where the said heteroaryl has 1-2 heteroatoms selected from nitrogen.

EFFECT: compounds can be used to prevent and treat diseases of the central nervous system, pathogenesis of which is associated with 5-HT6 receptors for enhancing mental capacity.

14 cl, 3 tbl, 19 dwg, 16 ex

FIELD: medicine.

SUBSTANCE: invention is related to application of therapeutically effective amount of flibanserin or its pharmacologically acceptable acid addition salts to produce a medicine for treating premenstrual disorders. The daily dosage of flibanserin is 0.1 to 400 mg a day.

EFFECT: effective treatment of premenstrual dystrophy, premenstrual mood disorders.

4 cl, 12 ex

FIELD: chemistry.

SUBSTANCE: described are novel compounds with general formula , their stereoisomers and pharmaceutically acceptable salts or solvates, where the dashed line can represent a double bond (together with the present single bond); R represents phenyl or benzodioxolyl, each of which can be substituted; R1, R3 and R4 independently represent hydrogen or C1-C6alkyl; R5 represents C1-C6alkyl; R7 represents hydrogen; R12 represents R3 or -C(O)R2, where R2 represents C1-C4 alkyl; D and G represent -CH2 - or -CH- when they are bonded to each other by a double bond; m equals 1; a pharmaceutical composition containing said compounds, and use of the novel compounds in treating conditions mediated by corticotropin-releasing factor (CRF).

EFFECT: increased effectiveness of compounds.

11 cl, 13 ex, 11 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula or to any isomer thereof, or mixture of isomers thereof, or pharmaceutically acceptable salt thereof, where R1 represents hydrogen or alkyl; R2 and R3 together form -(CH2)2-, and R2' and R3' represent hydrogen, m equals 1; n equals 1; X represents -O-; and Q represents chroman-2-on-7-yl, which is possibly substituted with one or more substitutes independently selected from a group consisting of halogen, trifluoromethyl, trifluoromethoxy, cyano, hydroxy, amino, nitro, alkoxy, cycloalkoxy, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl and alkynyl. The invention also relates to a pharmaceutical composition, as well as to use of chemical compound in any of paragraphs 1-4.

EFFECT: obtaining novel biologically active compounds having monoamine neuromediator reuptake inhibitory activity.

8 cl, 10 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: invention refers to compound of formula I wherein X represents -S- or -NH-; R1 represents C1-12alkyl, C2-12alkenyl, phenyl C1-12alkel, phenyl C2-12alkenyl or phenyl-O-C1-12alkyl and wherein said phenyl groups are optionally substituted with one or two assistants chosen from the group consisting of lower C1-7alkyl, C C1-7alkoxy and halogen C1-7alkyl; R2 represents hydrogen, lower C1-7alkyl or C3-6cycloalkyl; R3/R4 together with N-atom whereto attached, form nonaromatic 5,6-members heterocyclic ring system which optionally contains in addition to N-atom one additional heteroatom chosen from the group, consisting of O or N and where the ring system is optionally substituted group lower C1-7alkyl, lower C1-7alkoxy, -NR2, -CONR2; or R3/R4 together with N-atom whereto attached, can form heterocyclic ring system which contains at least two rings and which optionally contains one or two additional heteroatoms chosen from group, consisting of N and O; R represents hydrogen or lower C1-7alkyl; R5 represents hydrogen or lower C1-7alkyl; or to pharmaceutically acceptable additive salts with acid of this compound. The invention also concerns a medical product.

EFFECT: improved clinical effectiveness.

16 cl, 4 dwg, 3 tbl, 43 ex

FIELD: medicine.

SUBSTANCE: invention concerns medicine, namely psychiatry, and covers treatments of antidepressions. That is ensured by combined action of selective serotonin reuptake inhibitors (SSRUI) and phototherapy. Thus from the very beginning of the therapy, SSRUI is administered in standard therapeutic doses without dose selection. In addition, negative-ion aeroionotherapy is implemented. Photo- and aeroionotherapy are performed in a phototherapy room of the area 14 m2, at total light intensity 2500 lux, and aeroion concentration 1×105/cm3, in the morning and in the evening with session duration 1.5 hours.

EFFECT: higher effectiveness and reduced treatment time both in seasonal, and nonseasonal pattern clinical course of depression.

2 ex, 4 dwg

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to pharmaceutical industry and concerns an antidepressant composition containing medicinal substance based on Azaphen. The composition contains the following components, mg/tbl: Azaphen 155.4-158.7; Metocel 80.0-100.0; Microcrystalline cellulose 98.7-102.0; Aerosil 3.7-14.8; Kollidon 25 3.7-11.1; Talc 5.55-11.1; Magnesium stearate 1.85-3.7.

EFFECT: invention provides production of the pharmaceutical composition with prolonged release of the active pharmaceutical component that allows stabilising concentration of the preparation in a human body within 24 hours and thereby reducing frequency rate of the preparation intake within 24 hours to attain the required therapeutic effect.

2 cl, 3 ex, 1 tbl, 1 dwg

FIELD: pharmacology.

SUBSTANCE: invention covers new compounds of formula I: or its pharmaceutically acceptable salt with antagonist activity to corticotrophin release factor (CRF). In formula (I) X means heteroaryl chosen of pyrazolyl and imidazolyl optionally substituted with (C1-C6)alkyl, haloid or phenyl; Y means -NRaRb where Ra means hydrogen, and Rb means phenyl optionally substituted with (C1-C6)alkyl or haloid; Z means (C1-C6)alkyl; and R1 means hydrogen, (C1-C6)alkyl or haloid.

EFFECT: compounds can find application in treatment, eg of neurodegenerative diseases, neuropsychiatric disorders and stresses.

19 cl, 1 dwg, 2 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: invention is related to antagonists of serotonin 5-HT6 receptors of common formula 1 and their pharmaceutically acceptable salts and/or hydrates, pharmaceutical compositions, dosage forms and methods of production. Invention also includes new compounds of formula 1.1. In formulae 1 and 1.1 , Ar represents aryl, selected from unnecessarily substituted phenyl or unnecessarily substituted 5-6-member heteroaryl, which contains atom of nitrogen or atom of sulfur and heteroatom; R1 represents atom of hydrogen, unnecessarily substituted C1-C5 alkyl; Ar represents aryl, selected from unnecessarily substituted phenyl or unnecessarily substituted 5-6-member heteroaryl, which contains atom of nitrogen or atom of sulfur as heteroatom; R1 represents atom of hydrogen, which is unnecessarily substituted C1-C5 alkyl; R21,R22, R31, R32 independently from each other represent atom of hydrogen or substituent of aminogroup, selected from unnecessarily substituted C1-C4 alkyl, unnecessarily substituted phenyl, or R31 and R32 together with atom of nitrogen, to which they are bound, create unnecessarily substituted saturated 6-member heterocycle, possibly containing atom of nitrogen in cycle; or R1 together with atom of nitrogen, to which it is bound, and R21 and R22 together with atom of nitrogen, to which they are bound, create substituted pyrimidine cycle. In formula 1.1 R4, R5 and R6 independently from each other represent atom of hydrogen, unnecessarily substituted C1-C3 alkyl or phenyl.

EFFECT: compounds of invention may find application for treatment and prevention of development of conditions and disorders of central nervous system.

13 cl, 11 dwg, 4 tbl, 11 ex

FIELD: medicine.

SUBSTANCE: invention refers to method for prevention of mirtazapin sublimation from a pharmaceutical preparative form containing solid enantiomer pure form of mirtazapin, by making the preparative forms by addition of at least one pharmaceutically acceptable adjuvant to the solid form of mirtazapin enantiomer. The enantiomer pure form is pharmaceutically acceptable, nonsublumating and solid salt of S- or R-mirtazapin. There are also described nonsublumating salts of S-mirtazapin and the pharmaceutical preparative form of the latter.

EFFECT: higher efficiency of the composition.

4 cl, 4 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted cycloalkene derivatives of formula (I) in which X and Y are a group, in which X and Y together with a carbon atom on ring B to which they are bonded form a ring A, X and Y together represent a ring B substitute, or each of X and Y is a hydrogen atom.

EFFECT: invention relates to a medicinal agent based on the said compounds, which has inhibitory effect on intracellular signal transduction or cell activation induced by an endotoxin.

21 cl, 3 tbl, 191 ex

Up!