Composition containing protein material and compounds which contain unoxidisable structural elements of fatty acids

FIELD: medicine.

SUBSTANCE: invention relates to pharmacology. Application of preparation which contains combination: 1) fermented and/or hydrolysed protein material, and 2) one or several compounds, which contain unoxidisable structural unit of a fatty acid, for obtaining pharmaceutical or food composition, as well as composition for prevention and/or treatment of resistance to insulin, obesity, diabetes, fatty infiltration of the liver, hypercholesterolemia, dyslipidemia, atherosclerosis, coronary heart disease, thrombosis, stenosis, secondary stenosis, myocardium infarction, stroke, hypertension, endothelial dysfunction, state of hypercoagulability, polycystic ovary syndrome, metabolic syndrome, malignant tumour, inflammatory disorder and proliferative skin disturbance. Application of animal food containing common food components and combination of: 1) fermented and/or hydrolysed protein material, and 2) one or several compounds which contain structural elements of fatty acids which cannot be β-oxidised for improvement of general lipid composition in animal organism. Method of obtaining product of animal origin with improved composition of fatty acids, which includes feeding of the animal intended for product obtaining, with animal food which contains common food components and combination of: 1) fermented and/or hydrolysed protein material, and 2) one or several compounds which contain structural elements of fatty acids which cannot be β-oxidised. Invention also relates to application of preparation which contains combination of: 1) protein material and 2) oil or fish oil for prevention of said diseases, and to composition for prevention and/or treatment of hypercholesterolemia and states which are negatively influenced by said diseases, which contains said combination.

EFFECT: invention ensures increase of efficiency of prevention and treatment of said diseases.

82 cl, 12 tbl, 3 ex

 

The SCOPE of the INVENTION

It was shown that the use of combinations is not exposed to β-oxidation of structural elements, fatty acids and protein material are achieved unexpected synergistic effects. The present invention relates to compositions obtained by mixing compounds containing not undergo β-oxidation of structural elements fatty acids and protein material, and to use this composition for the manufacture of a pharmaceutical or nutritional composition for the prevention and/or treatment of insulin resistance, obesity, diabetes, fatty infiltration of the liver, hypercholesterolemia, dyslipidemia, atherosclerosis, coronary heart disease, thrombosis, stenosis, secondary stenosis, myocardial infarction, stroke, elevated blood pressure, endothelial dysfunction, a condition of high blood coagulability, polycystic ovarian syndrome, metabolic syndrome, malignant tumors, inflammatory disorders and proliferative skin disorders. This composition can also be used as an additional component in nutrition for daily feeding of animals in order to influence the composition of their body in General, specifically on the fatty acid composition.

BACKGROUND of the INVENTION

In earlier patent applications of the inventor described l the educational use is not exposed to β-oxidation analogues of fatty acids according to the present invention for the treatment and prevention of obesity (2000 NO 5461), diabetes (NO 2000 5462), primary and secondary stenosis (NO 2000 5463), malignant tumors (NO 2002 5930), proliferative skin disorders (2003 NO 1080), inflammatory and autoimmune disorders (2003 NO 2054). In other earlier patent applications of the inventor described therapeutic use of the protein material of the present invention, including proteins of unicellular organisms (2003 NO 3082) and protein hydrolysate fish (2003 NO 3078).

Unexpectedly, the authors of the present invention have shown that the use of combinations is not exposed to β-oxidation of the structural elements of the fatty acids with the protein material is achieved synergistic beneficial biological effects. The inventors have shown that the combination is not exposed to β-oxidation of the structural elements of fatty acids with protein material leads to a decrease in plasma concentrations of cholesterol, triglycerides, and phospholipids and increased activity of acyl-CoA-oxidase fats. In addition, the inventors describe how not undergo β-oxidation of structural elements fatty acids and protein material can be added directly to animal feed. Food is easily digested, and it was shown unexpected effect on the composition of fatty acids in animals. Based on these unexpected discoveries, it is expected that the combination is not powerhouse the Xia β-oxidation of structural elements, fatty acids and protein material will have an increased preventive and/or therapeutic effect on all diseases, against which it is effective is not exposed to β-oxidation of structural elements fatty acids, compared with the effect of the structural elements of the fatty acids in particular.

BRIEF description of the INVENTION

This invention relates to the use of the drug containing a combination of:

1) fermented and/or hydrolyzed protein material

2) one or more compounds containing not undergo β-oxidation structural element fatty acids, presents

(a) the General formula R-COO-(CH2)2n+1-X-R', where X represents a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group SO or group SO2; n is a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, where the main chain of the specified R' contains from 13 to 23 carbon atoms and optionally one or more heterogroup selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group and SO the group of SO2; and R" represents a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms; provided that at least one X is not CH2and/or

(b) the General formula (I),

where R1, R2 and R3 represented Aut a

(i) a hydrogen atom; or

ii) a group of the formula CO-R, where R is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of the specified R contains from 1 to 25 carbon atoms; or

iii) a group of the formula-(CH2)2n+1-X-R', where X represents a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group SO or group SO2; n is a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, where the main chain of the specified R' contains from 13 to 23 carbon atoms and optionally one or more heterogroup selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group and SO the group of SO2;

iv) a structural element selected from the group consisting of - PO3CH2CHNH3COOH (phosphatidylserine), PO3CH2CH2NH3(phosphatidylethanolamine), PO3CH2CH2N(CH2)3(phosphatidylcholine), PO3CH2CHOHCH2OH (phosphatidylglycerol) and RHO3(SNON)6(phosphatidylinositol); where R1, R2, and R3 are chosen independently from i), ii), iii) or iv), but at least one of R1, R2, or R3 is defined as (iii); provided that at least one X is not CH2 and/or

(C) the General formula (II)

where A1, A2 and A3 are chosen independently and represent an oxygen atom, a sulfur atom or a group N-R4, in which R4 represents a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 5 carbon atoms;

where R1, R2 and R3 represent

(i) a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 23 carbon atoms; or

ii) a group of the formula CO-R in which R represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of the specified R contains from 1 to 25 carbon atoms; or

iii) a group of the formula-(CH2)2n+1-X-R', where X represents a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group SO or group SO2; n is a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, where the main chain of the specified R' contains from 13 to 23 carbon atoms and optionally one or more heterogroup selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2the group and SO the group of SO 2;

iv) a structural element selected from the group consisting of - PO3CH2CHNH3COOH (phosphatidylserine), PO3CH2CH2NH3(phosphatidylethanolamine), PO3CH2CH2N(CH2)3(phosphatidylcholine), PO3CH2CHOHCH2OH (phosphatidylglycerol) and RHO3(SNON)6(phosphatidylinositol);

where R1, R2, and R3 are chosen independently from i), ii), iii) or iv), but at least one of R1, R2, or R3 is defined as (iii); provided that at least one X is not CH2and/or

salt, prodrug or complex compounds according to paragraphs.(a)-(C) to obtain a pharmaceutical or food compositions for the prevention and/or treatment of insulin resistance, obesity, diabetes, fatty infiltration of the liver, hypercholesterolemia, dyslipidemia, atherosclerosis, coronary heart disease, thrombosis, stenosis, secondary stenosis, myocardial infarction, stroke, elevated blood pressure, endothelial dysfunction, a condition of high blood coagulability, polycystic ovarian syndrome, metabolic syndrome, malignant tumors, inflammatory disorders, and proliferative disorders of the skin.

Preferably, the prevention and/or treatment of a malignant tumor involves inhibition: primary and secondary tumors, the growth of tumors is her invasion of the primary tumor in the connective tissue and the formation of secondary tumors; inflammatory violation is selected from the group consisting of immune disorders such as rheumatoid arthritis, systemic vasculitis, systemic lupus erythematosus, systemic sclerosis, dermatomyositis, polymyositis, various autoimmune endocrine disorders (e.g., thyroiditis and adrenalin), various immune neurological disorders (e.g. multiple sclerosis and myasthenia gravis), various cardiovascular disorders (e.g., myocarditis, congestive heart failure, arteriosclerosis, and stable and unstable angina and Wegener's granulomatosis), inflammatory bowel disease and Crohn's disease, nonspecific colitis, pancreatitis, nephritis, cholestasis/fibrosis of the liver, acute and chronic graft rejection after organ transplantation and diseases that have an inflammatory component, such as, for example, Alzheimer's disease or impaired/is able to improve cognitive function.

Specified proliferative disorder skin selected from the group consisting of psoriasis, atopic dermatitis, non-specific dermatitis, primary irritant contact dermatitis, allergic contact dermatitis, lamellar ichthyosis, epidermolizei hyperkeratosis pre-malignant induced by the action of solar keratosis and seborrhea.

Further, the invention relates to the use of animal feed containing common food components and the combination of:

1) fermented and/or hydrolyzed protein material

2) one or more compounds containing not undergo β-oxidation of structural elements fatty acids, presents

(a) the General formula R-COO-(CH2)2n+1-X-R', where X represents a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group SO or group SO2; n is a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, where the main chain of the specified R' contains from 13 to 23 carbon atoms and optionally one or more heterogroup selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group and SO the group of SO2; and R" represents a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms; provided that at least one X is not CH2and/or

(b) the General formula (I),

where R1, R2 and R3 represent

(i) a hydrogen atom; or

ii) a group of the formula CO-R, where R is a linear or branched alkyl group, saturated or unsaturated, neo is Astelin substituted, and the main chain of the specified R contains from 1 to 25' carbon atoms; or

iii) a group of the formula-(CH2)2n+1-X-R', where X represents a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group SO or group SO2; n is a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, where the main chain of the specified R' contains from 13 to 23 carbon atoms and optionally one or more heterogroup selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group and SO the group of SO2;

iv) a structural element selected from the group consisting of - PO3CH2CHNH3COOH (phosphatidylserine), PO3CH2CH2NH3(phosphatidylethanolamine), PO3CH2CH2N(CH2)3(phosphatidylcholine), PO3CH2CHOHCH2OH (phosphatidylglycerol) and RHO3(SNON)6(phosphatidylinositol);

where R1, R2, and R3 are chosen independently from i), ii), iii) or iv), but at least one of R1, R2, or R3 is defined as (iii); provided that at least one X is not CH2and/or

(C) the General formula (II)

where A1, A2 and A3 are chosen independently and represent an oxygen atom, a sulfur atom or a group N-R4, in which a is Oh, R4 represents a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 5 carbon atoms;

where R1, R2 and R3 represent

(i) a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 23 carbon atoms; or

ii) a group of the formula CO-R, where R is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of the specified R contains from 1 to 25 carbon atoms; or

iii) a group of the formula-(CH2)2n+1-X-R', where X represents a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group SO or group SO2; n is a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, where the main chain of the specified R' contains from 13 to 23 carbon atoms and optionally one or more heterogroup selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group and SO the group of SO2;

iv) a structural element selected from the group consisting of - PO3CH2CHNH3COOH (phosphatidylserine), PO3CH2CH2NH3(phosphatidylethanolamine), PO3CH2CH2N(CH3)3(phosphatidylcholine), P 3CH2CHOHCH2OH (phosphatidylglycerol) and RHO3(SNON)6(phosphatidylinositol);

where R1, R2, and R3 are chosen independently from i), ii), iii) or iv), but at least one of R1, R2, or R3 is defined as (iii); provided that at least one X is not CH2and/or

salt, prodrug or complex compounds according to paragraphs.(a)-(C) to improve the overall composition of lipids in the body of the animal.

Preferably, the improvement in the overall composition of lipids involves reducing the overall level of lipids in the body, more preferably, a decrease in the total level of saturated fatty acids in the body or increase the overall level of n-3 fatty acids in the body.

While specified protein material selected from the group comprising proteins of unicellular organisms (SCP), hydrolyzed fish proteins and fermented protein material is soy, in particular, Gendaxin®.

Further, the compound containing not undergo β-oxidation structural element fatty acids is not exposed (3-oxidation of fatty acid, in particular, tetradecylthioacetic acid (TTA), tetrazacyclooctane acid and/or 3-thia-15-heptadecyl; and X represents a sulfur atom or a selenium atom.

The compound containing not undergo β-oxidation structural element fatty acids, can represent Stolypin, where specified phospholipid selected from the group consisting of phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol and/or diphosphatidylglycerol.

More specifically, a compound containing not undergo β-oxidation structural element fatty acids may be a derivative of phosphatidylcholine 1,2-ditetradecyl-sn-glycero-3-phosphocholine derived phosphatidylethanolamine 1,2-ditetradecyl-sn-glycero-3-phosphoethanolamine, or mono-, di - or triacylglyceride, in particular, triacylglyceride containing tetradecylthioacetic acid (TTA).

The composition according to the invention can additionally include vegetable and/or fish oil, which contains polyunsaturated fatty acids, for example, sunflower oil, soybean oil and olive oil.

Preferably, the above composition is injected or give food to an animal or person. The animal can be an agricultural animal, such as chicken, mammals, related to cattle, sheep, goats or pigs, or pet, such as dog or cat; in addition, the specified animal can be a fish or shellfish such as salmon, cod, tilapia, clams, oysters, lobster or crabs.

Daily dose of the compounds, the soda is containing not exposed to β-oxidation of structural elements fatty acids is about 1-200 mg/kg, preferably 5-50 mg/kg for human consumption, and about 1-2000 mg/kg, preferably 5-500 mg/kg, for consumption by animals.

Daily dose of protein material is about 5-500 mg/kg, preferably 50-300 mg/kg for human consumption, and from 5 mg/kg up to a total per diem of protein for consumption by animals.

Daily dose of oil is approximately 1-300 mg/kg, preferably 10-150 mg/kg for human consumption and from 1 mg/kg up to a total per diem of fats for consumption by animals.

Animal feed according to the invention may be a food composition, veterinary composition, and/or functional food product.

Further, the invention relates to compositions for the prevention and/or treatment of insulin resistance, obesity, diabetes, fatty infiltration of the liver, hypercholesterolemia, dyslipidemia, atherosclerosis, coronary heart disease, thrombosis, stenosis, secondary stenosis, myocardial infarction, stroke, elevated blood pressure, endothelial dysfunction, a condition of high blood coagulability, polycystic ovarian syndrome, metabolic syndrome, malignant tumors, inflammatory disorders, and proliferative disorders of the skin, where this composition contains a combination of:

1) fermentativnogo/or hydrolyzed protein material

2) one or more compounds containing not undergo β-oxidation of structural elements fatty acids, presents

(a) the General formula R-COO-(CH2)2n+1-X-R', where X represents a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group SO or group SO2; n is a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, where the main chain of the specified R' contains from 13 to 23 carbon atoms and optionally one or more heterogroup selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group and SO the group of SO2; and R" represents a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms; provided that at least one X is not CH2and/or

(b) the General formula (I),

where R1, R2 and R3 represent

(i) a hydrogen atom; or

ii) a group of the formula CO-R, where R is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of the specified R contains from 1 to 25 carbon atoms; or

iii) a group of the formula-(CH2)2n+1-X-R', where X represents a sulfur atom, a selenium atom, a CI atom is the oxygen, the group of CH2group SO or group SO2; n is a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, where the main chain of the specified R' contains from 13 to 23 carbon atoms and optionally one or more heterogroup selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group and SO the group of SO2;

iv) a structural element selected from the group consisting of - PO3CH2CHNH3COOH (phosphatidylserine), PO3CH2CH2NH3(phosphatidylethanolamine), PO3CH2CH2N(CH2)3(phosphatidylcholine), PO3CH2CHOHCH2OH (phosphatidylglycerol) and RHO3(SNON)6(phosphatidylinositol);

where R1, R2, and R3 are chosen independently from i), ii), iii) or iv), but at least one of R1, R2, or R3 is defined as (iii); provided that at least one X is not CH2and/or

(C) the General formula (II)

where A1, A2 and A3 are chosen independently and represent an oxygen atom, a sulfur atom or a group N-R4, in which R4 represents a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 5 carbon atoms is;

where R1, R2 and R3 represent

(i) a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 23 carbon atoms; or

ii) a group of the formula CO-R in which R represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of the specified R contains from 1 to 25 carbon atoms; or

iii) a group of the formula-(CH2)2n+1-X-R', where X represents a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group SO or group SO2; n is a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, where the main chain of the specified R' contains from 13 to 23 carbon atoms and optionally one or more heterogroup selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group and SO the group of SO2;

iv) a structural element selected from the group consisting of - PO3CH2CHNH3COOH (phosphatidylserine), PO3CH2CH2NH3(phosphatidylethanolamine), PO3CH2CH2N(CH3)3(phosphatidylcholine), PO3CH2CHOHCH2OH (phosphatidylglycerol) and RHO3(SNON)6(phosphate elinotel);

where R1, R2, and R3 are chosen independently from i), ii), iii) or iv), but at least one of R1, R2, or R3 is defined as (iii); provided that at least one X is not CH2and/or

salt, prodrug or complex compounds according to paragraphs.(a)-(C).

Preferably, the above protein material selected from the group comprising proteins of unicellular organisms (SCP), hydrolyzed fish proteins and fermented protein material is soy (for example, Gendaxin®).

Also preferably, the composition according to the invention contains a daily dose of the compounds containing not exposed to β-oxidation similar fatty acid, about 1-200 mg/kg, preferably 5-50 mg/kg for human consumption and about 1-2000 mg/kg, preferably 5-500 mg/kg, for consumption by animals.

In addition, the composition may further contain plant and/or fish oil; compounds containing not undergo β-oxidation structural element fatty acids, is not exposed to β-oxidation of fatty acid, in particular, tetradecylthioacetic acid (TTA), tetrazacyclooctane acid and/or 3-thia-15-heptadecyl; and X represents a sulfur atom or a selenium atom.

In addition, the compound containing not undergo β-oxidation structural element fatty acids may be from the second phospholipid, selected from the group consisting of phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol, and/or diphosphatidylglycerol; or derived phosphatidylcholine 1/2-ditetradecyl-sn-glycero-3-phosphocholine; or a derivative of phosphatidylethanolamine 1,2-ditetradecyl-sn-glycero-3-phosphoethanolamine.

Alternatively, the compound containing not undergo β-oxidation structural component of the fatty acid is a mono-, di - or triacylglyceride containing tetradecylthioacetic acid (TTA).

In accordance with the invention, vegetable or fish oil contains polyunsaturated fatty acids and selected from the group consisting of sunflower oil, soybean oil and olive oil.

Preferably, the composition comprises a daily dose of protein material about 5-500 mg/kg, preferably 50-300 mg/kg for human consumption and from 5 mg/kg up to a total per diem of protein for consumption by animals.

In addition, the composition according to the invention can contain daily dose of oil approximately 1-300 mg/kg, preferably 10-150 mg/kg for human consumption and from 1 mg/kg up to a total per diem of fats for consumption by animals.

Thus the composition may be a food for animals, optionally containing General the adopted components of the feed, for example, food for fish, in particular, feed for salmon and common components of the feed containing fishmeal and/or fish oil.

The invention also relates to a method for obtaining a product of animal origin with the improved composition of fatty acids, providing for the feeding of an animal intended for the production of a product, animal feed, containing common food components and the combination of:

1) fermented and/or hydrolyzed protein material

2) one or more compounds containing not undergo β-oxidation of structural elements fatty acids displayed

(a) the General formula R-COO-(CH2)2n+1-X-R', where X represents a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group SO or group SO2; n is a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, where the main chain of the specified R' contains from 13 to 23 carbon atoms and optionally one or more heterogroup selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group and SO the group of SO2; and R" represents a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms; provided that at least one who is not CH 2and/or

(b) the General formula (I),

where R1, R2 and R3 represent

(i) a hydrogen atom; or

ii) a group of the formula CO-R, where R is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of the specified R contains from 1 to 25 carbon atoms; or

iii) a group of the formula-(CH2)2n+1-X-R', where X represents a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group SO or group SO2; n is a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, where the main chain of the specified R' contains from 13 to 23 carbon atoms and optionally one or more heterogroup selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group and SO the group of SO2;

iv) a structural element selected from the group consisting of - PO3CH2CHNH3COOH (phosphatidylserine), PO3CH2CH2NH3(phosphatidylethanolamine), PO3CH2CH2N(CH3)3(phosphatidylcholine), PO3CH2CHOHCH2OH (phosphatidylglycerol) and RHO3(SNON)6(phosphatidylinositol);

where R1, R2, and R3 are chosen independently from i), ii), iii) or iv), but at measures is one of the R1, R2, or R3 is defined as (iii); provided that at least one X is not CH2and/or

(C) the General formula (II)

where A1, A2 and A3 are chosen independently and represent an oxygen atom, a sulfur atom or a group N-R4, in which R4 represents a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 5 carbon atoms;

where R1, R2 and R3 represent

(i) a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 23 carbon atoms; or

ii) a group of the formula CO-R in which R represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of the specified R contains from 1 to 25 carbon atoms; or

iii) a group of the formula-(CH2)2n+1-X-R', where X represents a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group SO or group SO2; n is a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, where the main chain of the specified R' contains from 13 to 23 carbon atoms and optionally one or more heterogroup, select the data group, containing an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group and SO the group of SO2;

iv) a structural element selected from the group consisting of - PO3CH2CHNH3COOH (phosphatidylserine), PO3CH2CH2NH3(phosphatidylethanolamine), PO3CH2CH2N(CH3)3(phosphatidylcholine), PO3CH2CHOHCH2OH (phosphatidylglycerol) and RHO3(SNON)6(phosphatidylinositol);

where R1, R2, and R3 are chosen independently from i), ii), iii) or iv), but at least one of R1, R2, or R3 is defined as (iii); provided that at least one X is not CH2and/or

salt, prodrug or complex compounds according to paragraphs.(A.)-(C).

The above product of animal origin can be a meat product, the product is oil-based or product based on the skin.

Further, the invention relates to the use of the drug containing a combination of:

1) a protein material and

2) vegetable oil or fish oil, in which the protein material selected from the group comprising proteins of unicellular organisms (SCP), hydrolyzed fish proteins, fermented protein material is soy, preferably Gendaxin®, to obtain a pharmaceutical or nutritional composition for the prevention and/or treatment of hypercholesterolemia and conditions, to which were negatively affected by high cholesterol levels, insulin resistance, obesity, diabetes, fatty infiltration of the liver, dyslipidemia, atherosclerosis, coronary heart disease, thrombosis, stenosis, secondary stenosis, myocardial infarction, stroke, elevated blood pressure, endothelial dysfunction, a condition of high blood coagulability, polycystic ovarian syndrome, metabolic syndrome, malignant tumors, inflammatory disorders, and proliferative skin disorders.

The vegetable oil or fish oil contains polyunsaturated fatty acids, and vegetable oil is selected from the group consisting of sunflower oil, soybean oil and olive oil.

Indicated prevention and/or treatment of a malignant tumor, preferably, includes inhibition:

primary and secondary tumors, tumor growth, invasion of the primary tumor in the connective tissue and the formation of secondary tumors.

In accordance with the invention, an inflammatory disturbance is chosen from the group consisting of immune disorders such as rheumatoid arthritis, systemic vasculitis, systemic lupus erythematosus, systemic sclerosis, dermatomyositis, polymyositis, various autoimmune endocrine disorders (e.g., thyroiditis and adrenalin), various immune neurological disorders (e.g. the R, multiple sclerosis and myasthenia gravis), various cardiovascular disorders (e.g., myocarditis, congestive heart failure, arteriosclerosis, and stable and unstable angina and Wegener's granulomatosis), inflammatory bowel disease and Crohn's disease, nonspecific colitis, pancreatitis, nephritis, cholestasis/fibrosis of the liver, acute and chronic graft rejection after organ transplantation and diseases that have an inflammatory component, such as, for example, Alzheimer's disease or impaired/is able to improve cognitive function.

But such a proliferative disorder skin can be selected from the group consisting of psoriasis, atopic dermatitis, non-specific dermatitis, primary irritant contact dermatitis, allergic contact dermatitis, lamellar ichthyosis, epidermolizei hyperkeratosis, pre-malignant induced by the action of solar keratosis and seborrhea.

Preferably, the composition according to the invention is administered or give food to an animal or human, where the animal is an agricultural animal, such as chicken, mammals, related to cattle, sheep, goats or pigs; or a pet such as a dog or cat; in addition, the animal may be a fish or is oleskow, such as salmon, cod, tilapia, clams, oysters, lobster or crabs.

Daily dose of protein material may be approximately 5-500 mg/kg, preferably 50-300 mg/kg for human consumption, and from 5 mg/kg up to a total per diem of protein for consumption by animals.

Daily dose of oil can be approximately 1-300 mg/kg, preferably 10-150 mg/kg for human consumption and from 1 mg/kg up to a total per diem of fats for consumption by animals.

This pet food according to the invention may be a food composition, veterinary composition, and/or functional food product.

The invention further relates to compositions for the prevention and/or treatment of hypercholesterolemia and conditions, which negatively affected by high cholesterol levels, insulin resistance, obesity, diabetes, fatty infiltration of the liver, dyslipidemia, atherosclerosis, coronary heart disease, thrombosis, stenosis, secondary stenosis, myocardial infarction, stroke, elevated blood pressure, endothelial dysfunction, a condition of high blood coagulability, polycystic ovarian syndrome, metabolic syndrome, malignant tumors, inflammatory disorders, and proliferative disorders of the skin, containing a combination of:

1) alcoholically and

2) vegetable oil or fish oil,

in which the protein material selected from the group comprising proteins of unicellular organisms (SCP), hydrolyzed fish proteins, fermented protein material is soy, preferably Gendaxin®.

In this composition, vegetable oil or fish oil contains polyunsaturated fatty acids, and vegetable oil is selected from the group consisting of sunflower oil, soybean oil and olive oil.

The composition may contain a daily dose of protein material about 5-500 mg/kg, preferably 50-300 mg/kg for human consumption and from 5 mg/kg up to a total per diem of protein for consumption by animals.

Also, the composition may contain a daily dose of oil approximately 1-300 mg/kg, preferably 10-150 mg/kg for human consumption and from 1 mg/kg up to a total per diem of fats for consumption by animals.

Preferably, the composition may be a food for animals, optionally containing common components of the feed.

More preferably, the animal feed is a feed for fish, particularly salmon, and common components of the feed containing fishmeal and/or fish oil.

DETAILED description of the INVENTION

The present invention relates to the use of the drug, soteriades the combination of:

1) a protein material,

2) one or more compounds containing not undergo β-oxidation of structural elements fatty acids, presents

(a) the General formula R-COO-(CH2)2n+1-X-R', where X represents a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group SO or group SO2; n is a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, where the main chain of the specified R' contains from 13 to 23 carbon atoms and optionally one or more heterogroup selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group and SO the group of SO2; and R" represents a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms; and/or

(b) the General formula (I),

where R1, R2 and R3 represent

(i) a hydrogen atom; or

ii) a group of the formula CO-R in which R represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of the specified R contains from 1 to 25 carbon atoms; or

iii) a group of the formula CO-(CH2)2n+1-X-R', where X represents a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group or SO GRU is PU SO 2; n is a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, where the main chain of the specified R' contains from 13 to 23 carbon atoms and optionally one or more heterogroup selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group and SO the group of SO2;

iv) a structural element selected from the group consisting of-PO3CH2CHNH3COOH (serine), PO3CH2CH2NH3(ethanolamine), PO3CH2CH2N(CH3)3(choline), PO3CH2CHOHCH2OH (glycerol) and PO3(CHOH)6(Inositol); where R1, R2, and R3 are chosen independently from i), ii), iii) or iv), but at least one of R1, R2, or R3 is defined as (iii); and/or

(c) the General formula (II)

where A1, A2 and A3 are chosen independently and represent an oxygen atom, a sulfur atom or a group N-R4, in which R4 represents a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 5 carbon atoms;

where R1, R2 and R3 represent

(i) a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 is about 23 carbon atoms; or

ii) a group of the formula CO-R in which R represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of the specified R contains from 1 to 25 carbon atoms; or

iii) a group of the formula CO-(CH2)2n+1-X-R', where X represents a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group SO or group SO2; n is a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, where the main chain of the specified R' contains from 13 to 23 carbon atoms and optionally one or more heterogroup selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group and SO the group of SO2;

iv) a structural element selected from the group consisting of-PO3CH2CHNH3COOH (serine), PO3CH2CH2NH3(ethanolamine), PO3CH2CH2N(CH3)3(choline), PO3CH2CHOHCH2OH (glycerol) and PO3(CHOH)6(Inositol);

where R1, R2 and R3 are chosen independently from i), ii), iii) or iv), but at least one of R1, R2, or R3 is defined as (iii); and/or

salt, prodrug or complex compounds according to paragraphs. (a)-(c).

In a preferred embodiment, compounds according to this image the structure of at least one of R1, R2 or R3 represents alkyl.

In a preferred embodiment, compounds according to this invention, at least one of R1, R2 or R3 represents an alkene.

In a preferred embodiment, compounds according to this invention, at least one of R1, R2 or R3 is an alkyne.

In a preferred embodiment, compounds according to this invention, at least one of R1, R2 or R3 represents tetradecylthioacetic acid.

In a preferred embodiment, compounds according to this invention, at least one of R1, R2 or R3 represents tetrazacyclooctane acid.

The preferred options for the implementation of the compounds according to this invention are not exposed to β-oxidation of fatty acids.

In a preferred embodiment, compounds according to this invention, X represents a sulfur atom or a selenium atom.

The preferred options for the implementation of the compounds according to this invention are tetradecylthioacetic acid (TTA), tetrazacyclooctane acid and 3-thia-15-heptadecan.

In a preferred embodiment, compounds according to this invention, n represents 0 or 1.

In a preferred embodiment, compounds according to this invention, the specified connection before the hat is a phospholipid, where specified phospholipid selected from the group consisting of phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol, diphosphatidylglycerol.

In a preferred embodiment, compounds according to this invention, the specified connection is triacylglycerol.

In a preferred embodiment, compounds according to this invention, the specified connection is a diacylglycerol.

In a preferred embodiment, compounds according to this invention, the specified connection is monoacylglycerol.

In a preferred embodiment, compounds according to this invention, the specified connection is a derivative of phosphatidylcholine (PC), 1,2-ditetradecyl-sn-glycero-3-phosphocholine.

In a preferred embodiment, compounds according to this invention, the specified connection is a derivative of phosphatidylethanolamine (PE), 1,2-ditetradecyl-sn-glycero-3-phosphoethanolamine.

The preferred options for the implementation of the compounds in this invention are mono-, di - or triacylglyceride.

The preferred options for the implementation of the compounds according to this invention are triacylglyceride containing tetradecylthioacetic acid (TTA).

In site Cetelem embodiment, the compounds of formula (II) each of A1 and A3 represents an oxygen atom, while A2 represents a sulfur atom or a group N-R4, in which R4 represents a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 5 carbon atoms.

The compounds of this invention are analogues of natural compounds and essentially recognized the same systems that process natural compounds, including enzymes, which carry out β-oxidation and in some cases, the ω-oxidation of natural long-chain fatty acids. Analogues differ from their natural counterparts in that they can not completely be oxidized in this way.

Compounds according to this invention can comprise not exposed to β-oxidation analogues of fatty acids, as represented by the formula R" - CO-(CH2)2n+1-X-R'. However, these connections can also be a more complex structure obtained from one or more of these is not exposed to β-oxidation analogues of fatty acids, as represented by the General formula (I) or (II). These compounds represent analogues of natural mono-, di - and triacylglycerides or phospholipids, including phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol and diphosphatidylglycerol. These connected the I also can contain a substitution in the backbone of glycerol, as shown in the formula (II). The specified substitution of oxygen(s) reach the replacement of oxygen(s), group containing sulfur or nitrogen. This may prevent hydrolysis before capture in the small intestine, thereby increasing the bioavailability of the compounds.

The above complex structure obtained from one or more of these is not exposed to β-oxidation of structural elements fatty acids exert their effect because they contain analogues of fatty acids, which are not able to complete β-oxidation. These complex patterns can have an effect as whole structures as formed due to natural degradation products containing analogues of fatty acids. Due to the fact that the compounds are not able to complete β-oxidation, they accumulate and it starts increasing β-oxidation of natural fatty acids. Many of the effects of the compounds according to this invention are the result of such increase β-oxidation.

In the process of β-oxidation enzyme oxidized fatty acid is cleaved between carbon atoms 2 and 3 (counting from the carboxyl end of the fatty acid)that removes two carbon atoms on each side of the site of oxidation in the form of acetic acid. This stage is then repeated with the newly shortened to two ATO is and carbon fatty acid and again, until, while the fatty acid is not oxidized completely. β-oxidation is the usual way, which in vivo is the catabolism of most fatty acids. Blocking β-oxidation compounds according to this invention achieve the embedding is not exposed to oxidation of the group in the position X of the formula of the present invention. Due to the fact that the mechanism of β-oxidation is well known, X is defined as S, O, SO, SO2CH2or Se. The person skilled in the art may permit, without inventive step, that these connections will block β-oxidation in the same way.

In addition, the compounds may contain more than one block, i.e. in addition to X, R' may optionally contain one or more heterogroup selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group and SO the group of SO2. As an example, in order to cause changes in the degradation of fatty acids and, thus, to obtain a modulated effect, as X can be embedded two or three atoms of sulfur. A large number of sulfur atoms to some extent changes the polarity and stability. From a pharmacological point of view to avoid or prevent problems related to sustainability, as a rule, more desirable to be able to get laboroatory, than only one connection.

In addition to the structure of X, its position is also discussed. The distance from X to the carboxyl end of the fatty acid is determined by what number of groups CH2is between X and carboxyl end of the fatty acid, which is defined as (CH2)2n+1where n is a number from 0 to 11. Thus, it appears an odd number of groups CH2then there is the X-position relative to the carboxyl group, in which X in the end blocks β-oxidation. The range of values of n is chosen to include all variants of similar fatty acids, which possesses the desired biological effect. Since, theoretically, β-oxidation can act on molecules of unlimited length, n can represent an infinite value, but in practice it is not. Length fatty acids, which normally undergo β-oxidation, typically ranges from 14 to 24 carbon atoms, and such length, therefore, is optimal for the implementation of the enzyme β-oxidation. Thus, the ranges of n and R' refer to the structural elements fatty acids encompassed by this range. (Likewise, in order to obtain analogues of natural compounds option ii) of formula (I) and (II) determines R, as having from 1 to 25 carbon groups, and parameter) of the formula (II) determines alkyl group, as containing from 1 to 23 carbon atoms.) The total number of carbon atoms in the skeleton of the fatty acid is preferably between 8 and 30, most preferably between 12 and 26. This size range is also desirable to capture the structural elements of the fatty acids according to the present invention and their transport across the cell membrane.

Despite the fact that the analogues of fatty acids with an odd position blocker β-oxidation X, remote from the carboxyl end, inhibit oxidation, the value of their biological effect may vary. This is due to the time differences of biological degradation for different compounds. The inventors conducted experiments to show the effect further removal of X from the carboxyl end of the fatty acid. In these experiments, the activity (nmol/min/mg/protein) mitochondrial β-oxidation analogues of fatty acids in the liver was measured in the presence of sulfur in 3, 5 and 7 positions relative to the carboxyl end. The activity was 0.81 for sulfur in the 3 position, and 0.61 for sulfur in the 5-position of 0.58 for sulfur in the 7-position and 0.47 for palmitic acid, not blocking β-oxidation control. As expected, this shows that β-oxidation is really locked analogs of fatty acids with different position of the block, and that their effect decreases with further UD is through the block position from the carboxyl end, due to the fact that more time is required to achieve a block in β-oxidation, so that by the time are degraded larger amount of fatty acids. However, because the deviation is significant in the transition from 3 to 5 position, but small at the transition from 5 to 7 position, it can reasonably be assumed that during the movement along the chain, this deviation will be further reduced, and thus that the time isn't going to be any effect (compared with control), the situation will certainly be more remote.

Thus, it is reasonable to include as compounds of the present invention the structural elements of the fatty acids and other compounds represented by the General formulas (I) and (II), (which contain the specified analog(and fatty acids)that block β-oxidation at different distances from the carboxyl end counterparts, as the compounds of the present invention, is really blocking β-oxidation, even if the effect can be modulated. This modulation ultimately may vary with debilitating conditions; in various tissues, by exhausting the dosages, and the change of similar fatty acids, so it is not easily broken, as described below. Thus, it is reasonable inclusion in the formula of all is astani blocker β-oxidation from the carboxyl end of similar fatty acids, which are biologically suitable.

Despite the fact that the structural elements fatty acids, as described, with a block at position X cannot undergo β-oxidation, they nonetheless may be exposed ω-oxidation. It is significantly less flexible and slower biological process in which the oxidation of fatty acids is not with the carboxyl end, and preferably with a methyl/hydrophobic end group, here denoted R'. At this stage the carbon atom with the ω-end of the fatty acid hydroxylases a member of the family of cytochrome P450. Then this gidrauxilirovannaya fatty acid is converted by alcoholdehydrogenase in the aldehyde, and then the aldehyde is converted by aldehyddehydrogenase in the carboxyl group. As a result, the final product of the cascade is a dicarboxylic fatty acid, which may further degradirovali ω-oxidation with ω-end.

Suppose that ω-oxidation is the main degradation pathway of structural elements fatty acids, as described, with the block in position X. Thus, the conducted experiments, where R' has changed to block ω-oxidation introduction of a triple bond in the methyl end of similar fatty acids. The result was similar fatty acid 3-thia-15-heptadecan for which testing were shown the following expected the s results: significantly increased the degradation in vivo. It is important for the application of the structural elements of the fatty acids in pharmaceutical drug because it may exacerbate the effects of undergoing β-oxidation of structural elements fatty acids, further reducing their decay.

On the other hand, as in the case of blocking β-oxidation, a common practice is to identify other structural elements fatty acids, which will block the ω-oxidation in exactly the same way, on the basis of knowledge about how ω-oxidation. For example, the double bond will have the same effect as a triple bond, and thus, determination of methyl/hydrophobic end groups of the molecule, denoted here R'is enabled, it can be saturated or unsaturated. Branching can also lead to blocking the oxidation, so that the group R' is defined as linear or branched.

In order blocking ω-oxidation of embedding a substituent R'specified R' may be substituted in one or several positions by heterogroup selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2, And SO the group of SO2. R' may also be substituted by one or more compounds selected from the group consisting of fluoride, chloride, hydroxy, C1-C4alkoxy, C1-C4Alki is thio, C2-C5acyloxy or C1-C4alkyl.

Thus, the compounds in accordance with the present invention are either fatty acids, similar to the natural fatty acids, which cannot undergo β-oxidation, or natural lipids, containing the indicated equivalents of fatty acids. It was shown that in vivo structural elements fatty acids strictly preferably embedded in the phospholipids. In some cases, it really is preferable to simulate the properties and to incorporate structural elements of fatty acids in natural lipids, such as mono-, di - and triglycerides and phospholipids. This leads to changes in the suction connection (when comparing fatty acids with fatty acids, embedded in a larger lipid structure), and may increase the bioavailability or stability.

For example, you can obtain a set of embedding fatty acids(acids), which are unable to undergo β-oxidation, in triacylglycerol. Such compounds covered by formula (I) and (II). In oral administration such triacylglyceride, for example, in the product feed for animals, it probably will be transported like any triacylglyceride of the small intestine in chylomicrons and from the liver into the blood fat values for storage in adipose tissue or muscle is x, heart or liver, with hydrolysis of triacylglycerides to glycerol and 3 fatty acids. Free fatty acids at this stage will be starting compound of the present invention, and will no longer be a set.

Other possible glycerophospholipids derivatives of fatty acids of the present invention include, but are not limited to, phosphatidylcholine, phosphatidylethanolamine, synthesised, phosphatidylserine and phosphatidylglycerol.

Another method of esterification of fatty acids detected in vivo, which can be easily used to obtain a complex compound of the present invention may be obtaining alcohol or polisport corresponding fatty acid, for example, you can derive sphingolipids, such as ceramide or sphingomyelin, obtain the corresponding amerosport. Like glycerophospholipids complexes, these complexes can be highly insoluble in water and less hydrophilic. These types of hydrophobic complexes of the present invention will be easier to pass through biological membranes.

Other possible polar complexes of the present invention can be, but are not limited to, lysophospholipid, fosfatidov acid, alkoxysilane, glyceroglycolipid, Gaglioti the s and cerebrosides.

Despite the fact that there may be large structural differences between the various compounds containing not undergo β-oxidation of structural elements of the fatty acids of the present invention, it can be expected that the biological functions of all these compounds are very similar because they all block the β-oxidation in a similar manner. This failure of structural elements fatty acids for β-oxidation (and in some cases, to the ω-oxidation) leads to the accumulation analogues in the mitochondria, which triggers β-oxidation in vivo natural fatty acids, which in turn leads to many of the biological effects of compounds containing the structural elements of the fatty acids of the present invention. (Berge RK et al. (2002) Curr Opin Lipidol 13(3):295-304).

Cascade β-oxidation of fatty acids is the main path of metabolism of fats. The initial and rate-limiting reaction is carried acyl-CoA-oxidase in peroxisome liver. Acyl-CoA oxidase catalyzes dehydrogenization acyl-CoA thioesters to the corresponding TRANS-2-enoyl-CoA. Similar fatty acid of the formula (I), tetradecylthioacetic acid (TTA), the inventors previously used for analysis of various biological effects of fatty acids. For the present invention were analyzed its effect on acyl-CoA oxidase, and takeeffect protein material, separately or in combination.

Specific protein material analyzed here, is a fermented protein material is soy. Also in the process of analysis by the authors of the present invention is a protein material unicellular organisms and hydrolyzed fish proteins. Despite the fact that these materials are complex and contain not only protein, the authors of the present invention believe that as the active ingredient is a protein structure, enhancing therapeutic effects are not exposed to β-oxidation of fatty acids according to the present invention. Based on the results for the fermented protein material is soy described here, the authors present invention expect similar results for protein material unicellular organisms and protein hydrolysate fish.

When analyzing the activity of acyl-CoA-oxidase for TTA separately, it was shown a significant increase in activity compared to the negative control. Fermented protein material is soy separately practically had no activity. But in a joint application TTA and fermented protein material is soy, the activity of acyl-CoA oxidase was more than two times higher compared to the activity of TTA separately. This increased TTA as activator acyl-CoA-oxidase fermented protein mate what Yalom soybeans were totally unexpected. Strengthening definitely could explain the additive effect of TTA and fermented protein material is soy; unexpected synergistic effect was much stronger.

For the present invention also analyzed the effect is not exposed to β-oxidation of structural elements fatty acids at the level of phospholipids in the plasma, and the effect of fermented protein material is soy, alone or in combination with TTA. TTA resulted in lower levels of phospholipids compared with the control, while the fermented protein material is soy essentially slightly increased the level of phospholipids. However, in case of joint application TTA and fermented protein material is soy, the level of phospholipids unexpectedly declined to a greater extent than the level for TTA separately. This increased fermented protein material is soy TTA as a means for reducing the level of phospholipids in the plasma, were totally unexpected. As in the case of the activity of acyl-CoA-oxidase strengthening also cannot be explained by the additive effect of TTA and fermented protein material is soy.

For the present invention also analyzed the effect is not exposed to β-oxidation of structural elements fatty acids, as well as the effect of the fermented protein material is soy, alone or in combination with TTA, n is the level of cholesterol in the plasma. Also analyzed the effects of fish oil separately, TTA, fermented protein material is soy, or TTA, and c fermented protein material is soy. It was shown that TTA separately leads to a significant reduction of cholesterol in the plasma, and fermented protein material is soy or fish oil separately also have the effect of reducing the level of cholesterol. For fermented protein material is soy and fish oil has also been shown to reduce cholesterol to a greater extent than each of them separately. Adding fish oil or fermented protein material is soy to TTA, the effect of reducing cholesterol levels were unexpectedly higher than the effect of TTA separately. While adding all three components: TTA, cod-liver oil and fermented protein material is soy, the effect of cholesterol reduction was greatest. This synergy between TTA, fish oil and fermented protein material is soy was completely unexpected.

It was shown that TTA reduces the level of triglycerides in the plasma due to the increased number of mitochondria and stimulate mitochondrial β-oxidation of normal saturated and unsaturated fatty acids to ketone bodies (Froyland L et al. (1997) J Lipid Res 38:1851-1858). For the present invention was to identify what about, this effect is additionally unexpectedly enhanced by the addition of fermented protein material is soy. In these experiments, the results for fermented soy protein was absolutely amazing and unexpected. TTA, as expected, reduces the level of triglycerides. Fermented soy protein separately essentially increases the level of triglycerides by 30% compared to control, but nevertheless enhances the effect of TTA in lowering the level of triglycerides by 50%. These synergistic effects were also very unexpected.

For the present invention analyzed the effect of feeding Atlantic salmon feed containing not undergo β-oxidation analogues of fatty acids, the normal components of the feed and fermented protein material is soy. In example 2.1, fish food consisted covered by the conventional feed pellets with fish oil, including TTA and fermented protein material is soy. This food is then used in example 2.2 as a power supply for Atlantic salmon, and the presence of TTA has beneficial effects on the thus obtained food for fish compared to the equivalent food without TTA (examples 2.3 and 2.4).

Commonly used feed pellets contain mainly forage fish flour, a little wheat and vitamin and mineral supplements. Oil, used to prevent the coating of the granules, it was also of marine origin, capelin, and contained different amounts mixed with him TTA. Table 1 describes the composition and chemical composition of diets. Food was a common food, well suitable for the analyzed species (in this example, Atlantic salmon), for which adding TTA were shown favorable effects.

As was previously shown in this application, TTA, put together with protein has the additional beneficial effect compared with the effect of TTA separately. The fact that conventional food is food high in fat and protein and low in carbohydrates, probably enhances the beneficial effects of TTA compared with the effects of TTA entered separately or together with food with lots of carbohydrates.

In example 2.4 we determined the effects of a particular protein material, fermented protein material is soy. Fermented protein material is soy get in the fermentation of soy beans. It contains modified and unmodified soy proteins and isoflavones and other soy. In the preferred embodiment, this invention uses the fermented protein material is soy Gendaxin®.

Table 2 shows the fatty acid composition of diets. In the fatty acid composition of diets there was quite nathnac the positive differences (all contained approximately 100% fish oil), the percentage of n-3 fatty acids (FA) were almost identical. The diet, which was added TTA, however, led to significant changes in the percentage of the composition of n-3 fatty acids of phospholipids (PL), triacylglycerol (TAG) and free fatty acids (FFA) in the gills, heart and liver of Atlantic salmon. The introduction of the TTA for 8 weeks also resulted in lower percentage of saturated FA in almost all lipid fractions. The percentage of n-3 FA, especially DHA, increased in the gills and heart, as you can see in example 2.3.

Atlantic salmon, which were fed a diet containing TTA, grew more slowly than fish fed the control diet. The level of lipids in the body of the fish fed the diet with the addition of TTA, was significantly lower than in fish fed the control diet.

There is a favorable impact on the health of individual fish fed feed according to this invention. Older fish may develop sclerosis of the arteries and lead to health problems, as a person, and lipid-lowering has a beneficial effect in this regard.

In General, I believe that lean meats, obtained by the method according to the present invention are useful in most species of animals, which are bred for consumption. So about the time, the effect of reducing the overall level of lipids in itself is primary. In addition, specific changes in fatty acid composition are particularly positive. It is generally recognized that the use of a smaller amount of saturated fatty acids is good for health, and an increased intake of n-3 is associated with health benefits for the whole body, reduce the risk of heart disease to anti-inflammatory effects and even to increase intelligence in children.

Other animal products derived from animals fed with the feed of the present invention, may also have beneficial effects. As an example, fish oil, thus obtained, will have pre nutritional composition compared to the oil from the fish that were fed a commercial diet. Other products, such as the skin of the fish, may also have positive effects observed in the improvement of the composition of the whole organism.

The level of fatty acids in the blood in norm is determined by the relative speeds of the breakdown of fats and esterification in adipose tissue and consumption of fatty acids in the muscles. Muscle fatty acids inhibit the consumption of glucose and oxidation. Increased levels of fatty acids and triacylglycerides in the blood and muscles, thus, correlates with obesity and resist what tostu to insulin, and with reduced ability to metabolize glucose (Olefsky JM (2000) J Clin Invest 106:467-472; Guerre-Millo M, et al. (2000) J Biol Chem 275:16638-16642). The authors of the present invention have demonstrated a stimulation of fatty acid oxidation and reduce the concentration of fatty acids in plasma are not exposed to β-oxidation of structural elements, fatty acids and protein material, also optionally containing an oil component. The authors of the present invention, therefore, expect that the composition of the present invention can be used for the prevention and treatment of insulin resistance and caused her disease (Shulman GI (2000) J Clin Invest 106(2):171-176). It was found that completely prevents TTA caused by a diet high in fat insulin resistance and obesity, and obesity, hyperglycemia, and insulin sensitivity in rats with obesity (Madsen M, et al. (2002) J Lipid Res 43 (5): 742-50). Due to an unexpected synergistic results found by the authors of the invention when used as TTA and protein material, and optional oil without confirming any explaining the obtained results to a specific theory, the authors present invention currently expect that this combination will be even more effective in the treatment of these conditions. The authors present invention also expect that the function effectively TTA will increase protein material, and optional oil in the treatment of similar diseases and disorders, including high blood pressure, elevated lipids and cholesterol, endothelial dysfunction, increased blood clotting, polycystic ovary syndrome and metabolic syndrome.

The family of receptor-activated proliferation peroxisome (PPAR)are pleiotropic regulators of cellular functions such as cell proliferation, differentiation, and homeostasis of lipids (Ye JM et al. (2001) Diabetes 50:411-417). The PPAR family consists of three subtypes; PPARα, PPARβ and PPARγ. TTA is a strong ligand for PPARα (Forman BM, Chen J, Evans RM (1997) Proc Natl Acad Sci 94:4312-4317; Gottlicher M et al. (1993) Biochem Pharmacol 46:2177-2184; Berge RK et al. (1999) Biochem J 343(1):191-197), and also activates PPARβ and PPARγ (Raspe E et al. (1999) J Lipid Res 40:2099-2110). As PPARα activator TTA stimulates the catabolism of fatty acids by increasing their consumption by the cells. Reduction of triglycerides in plasma by TTA causes switching of the metabolism of liver cells in the direction of PPARα regulated catabolism of fatty acids in mitochondria. (Graf HJ et al. (2003) J Biol Chem 278(33):30525-33). Although the effect of TTA on the level of triacylglycerides in the plasma is determined by the activation of PPARα, which is shown by the elimination of this effect in mice with PPARα knockout, fish oil does not cause reduction of triacylglyceride in the plasma even in mice with knockout (Dallongeville J e al. (2001) J Biol Chem 276:4634-4639).

Supplement the diet with n-3 polyunsaturated fatty acids, such acids found in fish oil, stimulates the activity of acyl-CoA-oxidase peroxisome liver and, thus, the oxidation of fatty acids in the liver and to a lesser extent in skeletal muscle (Ukropec J et al. (2003) Lipids 38(10):1023-9). It has been shown that a diet with increased content of fish oil increases both the activity and mRNA level of enzymes of fatty acid oxidation peroxisome and mitochondria of the liver (Hong DD et al. (2003) Biochim Biophys Acta: Mol Cell Biol Lipids 1635 (l):29-36). Fish oil caused an increase in the relative content of peroxy acyl-CoA oxidase in the liver but not in muscle of rats, and the authors suggested that this is due to the fact that n-3 fatty acids protect against induced fat insulin resistance by acting as ligands of PPARα inducyruya peroxisome proliferation in the liver (not intramuscular). The PPARα gene expression did not change. (Neschen S et al. (2002) Am J Physiol Endocrinol Metab 282:E395-E401)

As you can see in the above paragraphs, the biochemical details of how TTA protein material and optional oil affect the metabolism of fats, details not known. The effects may or may not be mediated by one, as TTA and oils may, for example, to act as ligands of PPARα or independently of PPARα. If they are pieces which have the same paths, you cannot expect to gain TTA oils, due to the fact that TTA is a strong activator of PPARα, which, as you might expect, will fully provide for the activation of PPARα. Even with the addition, the effect of TTA and oil combination will be unexpected. Even less is known about how protein affects β-oxidation or other aspects of fat metabolism. Thus, it is impossible to predict the effects of simultaneous administration of protein material and TTA. However, obtaining a synergistic effect of the above additive effect, as you can see for TTA and fermented protein material is soy in all trials according to the present invention, was very unexpected. Exposed β-oxidation of structural elements fatty acids have many effects, and the authors of the present invention do not know how they all occur, but based on the unexpected results of the present invention, the authors expect that they will all be enhanced protein material and optional oils, without proof of any particular theory.

Ligands of PPAR violate the proliferation of various cell lines of malignant tumors. In particular, it was found that TTA reduces the proliferation of many cell lines of malignant tumors (Berge K et al. (2001) Carcinogenesis 22:1747-1755; Abdi-Dezfuli F et al. (1997) Breast cancer Res Treat 45:229-239; Tronstad KJ et al. (2001) Biochem Pharmacl 61:639-649; Tronstad KJ et al. (2001) Lipids 36:305-313). This decline is associated with reduced levels of triacylglycerides (Tronstad KJ et al. (2001) Biochem Pharmacol 61:639-649) and is mediated by both PPAR-dependent and PPAR-independent pathways (Berge K et al. (2001) Carcinogenesis 22:1747-1755). Because fermented soy protein enhances the ability TTA to reduce the level of triacylglycerides, thus it is very likely that it will also enhance the antiproliferative effects of TTA, providing this improved ability TTA to prevention and treatment of malignant tumors. TTA can be used for the prevention and/or treatment of malignant tumors, including inhibition of primary and secondary tumors, tumor growth, invasion of the primary tumor in the connective tissue and the formation of secondary tumors (NO 2002 5930).

Typically, the PPAR agonists modulate the inflammatory response. TTA modulates the inflammatory response by suppressing the release of inflammatory cytokine interleukin-2 and suppression of PHA-stimulated proliferation of peripheral mononuclear cells (Aukrust P, et al. (2003) Eur J Clin Invest 33(5):426-33). Modulation of cytokine by TTA may be mediated by PPAR or a change in the level of prostaglandins, or modification mediated by lipid transfer signal, the last of these is also possible mechanism of action of polyunsaturated fatty acids, such as nah who are in oils. Now, when the inventors have found unexpected results in relation to the present invention, they, therefore, expect that the protein material and optional oil, in combination with not undergo β-oxidation of structural elements fatty acids will enhance the effect of the structural elements fatty acids on inflammatory disorders, including immune disorders such as rheumatoid arthritis, systemic vasculitis, systemic lupus erythematosus, systemic sclerosis, dermatomyositis, polymyositis, various autoimmune endocrine disorders (e.g., thyroiditis and adrenalin), various immune neurological disorders (e.g. multiple sclerosis and myasthenia gravis), cardio-vascular disorders (for example, myocarditis, congestive heart failure, arteriosclerosis, and stable and unstable angina, and Wegener's granulomatosis), inflammatory bowel disease, Crohn's disease, nonspecific colitis, pancreatitis, nephritis, cholestasis/fibrosis of the liver, acute and chronic graft rejection after organ transplantation, as well as proliferative disorders of the skin, such as psoriasis, atopic dermatitis, non-specific dermatitis, primary irritant contact dermatitis, allergic contact dermatitis, lamellar ichthyosis, epidermal the practical hyperkeratosis, pre-malignant induced by the action of the sun carats and seborrhea, and diseases that have an inflammatory component, such as Alzheimer's disease or impaired/is able to improve cognitive function.

Description of the DRAWINGS

Figure 1 shows that the increase in the activity of acyl-CoA fats TTA increases fermented protein material is soy.

Figure 2 shows that the effect of TTA in lowering the level of phospholipids increases fermented protein material is soy.

Figure 3 shows that the effect of TTA in lowering the cholesterol level increases fermented protein material is soy and fish oil.

Figure 4 shows that the effects of TTA in lowering the level of triacylglycerides amplified fermented protein material is soy.

DEFINITIONS USED IN the PROPOSAL

Animals

In this context, the term "animal" includes mammals, such as man and farmer (agricultural) animals, especially animals of economic importance, such as chicken, mammals, related to cattle, sheep, goats and pigs, especially animals, through which are suitable for human consumption products, such as meat, eggs and milk. Further assume that the term includes fish and shellfish, is aka as salmon, cod, tilapia, clams, oysters, lobster or crabs. The term includes domestic animals, such as dogs and cats.

Pet food

The term "pet food" refers to food for animals (as defined above). Pet food usually contains the appropriate amounts of fats, proteins, carbohydrates, vitamins and minerals necessary for the sustenance of a particular recipient animal, and may contain additional components to improve the taste, texture, color, odor, stability, shelf life, etc. or antibiotics or other components added for the benefit of the health of the animal. Pet food is preferably, but not necessarily represent dry substance, most preferably, granular substance. This also implies that the term "pet food" includes food composition, veterinary compositions, and/or functional food products for consumption by animals.

Meat

The term "meat" refers to the raw meat of any animal, as defined above. Thus, all species containing protein raw meat of mammals, birds, slaves and shellfish are considered meat. The term "meat product" refers to any meat product as defined above.

Vegetable fats and/or fish oil/u>

They include all kinds of oils of vegetable or marine origin, including, but not limited to, a fat or fixed oil, and essential or volatile oils, and any combination of them. They do not necessarily have to be in liquid form. Sunflower oil, which was used for the present invention, is actually the oil from the seeds and not from the flower.

Fish oil

This term includes all kinds of oils of marine origin.

Food composition

Understood that this term includes any consumed inside the substance, including, but not limited to, dietary supplements, functional foods, herbal supplements, etc. for the use of man and animals. The term also includes food products for human consumption and for animal feed, where the composition of the present invention is an optional component and not the main ingredient. This is especially true for feed for animals, where any food can be supplemented with the composition of the present invention, to achieve its biological effects.

Treatment

For pharmaceutical aspects of the application of this invention, the term "treatment" refers to reducing the severity of the disease.

About elastica

The term "prevention" refers to preventing the disease, i.e. the connection according to the present invention is administered prior to development of the condition. This means that the compounds of the present invention can be used as a prophylactic or as ingredients in food compositions in order to prevent the risk or development of this disease.

Fermentation

Decomposition of organic materials by microorganisms or enzymes, including hydrolysis.

Hydrolysis

Enzymatic or chemical cleavage, in which complex molecules are broken down into simpler elements of chemical reaction with water.

Proteins of unicellular organisms (SCP)

SCP is a material contained in unicellular microorganisms. In particular, the microorganisms can be a fungi, yeast and bacteria. The SCP material has a high relative content of proteins.

Hydrolyzed fish proteins (FPH), treated with enzymes

Material FPH is a protein hydrolysate obtained by the enzymatic material handling fish. The FPH material has a high relative content of proteins and peptides.

Fermented protein material is soy

Fermented protein material is soy get is the fermentation of soy beans. It contains modified and unmodified soy proteins and isoflavones, as well as other components of soy.

Food composition

Understood that this term includes used inside the material, including, but not limited to, dietary supplements, functional foods, herbal supplements, etc. for consumption by humans or animals. The term also includes food products for human consumption and animal feed, where the composition of the present invention is an optional component and is not the main ingredient. This is especially true for feed for animals, where any food can be supplemented with the composition of the present invention, to achieve its biological effects.

INTRODUCTION COMPOUNDS of the PRESENT INVENTION

As a pharmaceutical drug composition according to the present invention can be administered to an animal by any suitable means, including parenteral, intranasal, oral administration, or by absorption through the skin. It can be entered locally or systemically. A particular method of introduction of each tool depends on the history of recipient-a person or animal.

Examples of parenteral administration include subcutaneous, intramuscular, in trevenna, intra-arterial and intraperitoneal administration.

As General provisions, the total pharmaceutically effective amount of each is not exposed to β-oxidation of structural elements fatty acids, administered parenterally in a dose preferably is in the range from about 1 mg/kg/day to 200 mg/kg/day body weight of the patient for a person, although, as described above, it can be a significant therapeutic division. The dose of 5-50 mg/kg/day is the most preferred. Dose of fermented protein material is soy or other protein material 5-500 mg/kg/day is preferred, and the dose of 50-300 mg/kg/day is the most preferred. The dose of fish oil or other oil 1-300 mg/kg/day is preferred, and the dose of 10-150 mg/kg/day of fish oil or other oil is the most preferred.

Constant introduction, all of the compounds of the present invention, as a rule, impose a 1-4 injections per day or long-term subcutaneous infusions, for example, using a mini-dispenser. You can also use the solution from the bag for intravenous administration. The main factor in selecting an appropriate dose is the end result determined by the decrease in total body weight or the ratio of fat and muscle mass, or other Crete the holders of the measured control, or prevention of obesity or prevention of obesity-related conditions as determined appropriate by a qualified technician.

In the case of parenteral administration, in one embodiment, compounds of the present invention is manufactured by mixing each of them with the appropriate degree of purity, in a unit dosage injectable form (solution, suspension, or emulsion) with a pharmaceutically acceptable carrier, i.e. with a carrier that is non-toxic to recipients at the used doses and concentrations, and is compatible with other ingredients of the composition.

Typically, the composition is produced by combining compounds of the present invention with liquid carriers, or finely divided solid carriers, or with those, and with the other in a uniform and homogeneous mixture. Then, if necessary, the product shape desired drug. Preferably the carrier is a carrier for parenteral administration, more preferably, a solution that is isotonic with the blood of the recipient. Examples of such carriers include water, saline, ringer's solution and dextrose. Non-aqueous media, such as fatty oils and etiloleat, and liposomes are also suitable here.

If appropriate, the carrier signal is to contain a small number of additional components, such as substances that enhance isotonicity and chemical stability. Such substances are not toxic to the recipient in the used doses and concentrations, and include buffers such as phosphate, citrate, succinate, acetate buffer and other buffers on the basis of organic acids or their salts; antioxidants such as ascorbic acid; immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamic acid, aspartic acid, or arginine; monosaccharides, disaccharides, and other carbohydrates, including cellulose or its derivatives, glucose, mannose, or dextrins; chelating agents such as EDTA; alcohols based on sugars, such as mannitol or sorbitol; counterions such as sodium; and/or nonionic surfactants such as Polysorbate, poloxamer or PEG.

In the case of oral pharmaceutical compositions can be used such media, such as water, gelatin, gums, lactose, starches, magnesium stearate, talc, oils, polyalkylphenol, liquid paraffin and the like, Such a pharmaceutical preparation may be in the form of unit dosage forms and may further contain other therapeutically useful substances or conventional pharmaceutical adjuvants such as preservatives, stabil the congestion, emulsifiers, buffers, etc. Pharmaceutical preparations can be in conventional liquid forms such as tablets, capsules, pills, capsules and the like, in conventional dosage forms such as capsules, and in the form of suppositories, etc.

In addition, the compounds of the present invention, i.e. the analogues are not exposed to β-oxidation of fatty acids and proteins or analogues are not exposed to β-oxidation of fatty acids and protein material and oil, can be used in food preparations as defined above, in which case the dosage is not exposed to β-oxidation analogues of fatty acids is a dosage, as described for medicines or lower, while the amount of protein material and oil is preferably suitable for the manufacture of food and feed materials. As part of food composition and, especially, animal feed, oil and protein material can represent a significant part of the feed, and thus, have nutritional value, and also to enhance the effects are not exposed to β-oxidation analogues of fatty acids. Fish oil may include up to all fat nutrient composition, and fermented protein material is soy may include up to all the proteins of the food composition. In animal feed, quantity does not discriminate who I β-oxidation of similar fatty acids can be up to 10 times higher than in products for human consumption, i.e. up to 2 g/kg/day body weight of the animal. Such animals can be used for daily feeding of the animals. Fermented protein material is soy is especially suitable as a functional protein in food products, in particular, when using as Deputy natural plasma in animal feed and pet foods. The composition of animal feed may also contain additional ingredients such as fats, sugar, salt, flavorings, minerals, etc. in Addition, the product can be shaped pieces, similar to the natural pieces of meat in appearance and texture. The product of this invention has additional advantages in that it is easy to make with the content of the required nutritional supplements, it is easily digested by animals and has an attractive taste to animals.

EXPERIMENTAL PART

Getting not exposed to β-oxidation of structural elements fatty acids according to the present invention is described in detail in the earlier patent applications Norway No. 20005461, 20005462, 20005463 and 20024114 of the applicant. These documents also described toxicity studies TTA. The preparation of mono-, di - and triglycerides and nitrogen-containing lipids according to this invention is detailed described in the patent application U.S. No. 10/484350. The preparation of phospholipids, including serine, ethanolamine, choline, glycerol and Inositol according to this invention is described in detail in the earlier patent application Norway No. 20045562 of the applicant.

The experimental results below show that the protein material and/or oil essentially enhance biological effects are not exposed to β-oxidation analogues of fatty acids.

Example 1. Biological effects of the compositions of this invention in rats

1.1 Obtaining protein hydrolysate fish (FPH)

Raw materials

FPH received from the remnants of the muscle tissue of fish bone skeleton after butchering on the fillet. Skeletons without goals recently split into fillets of Atlantic salmon (Salmon Salar, L.) were obtained directly from the production line and was frozen at -20±2°C. Within one week of the frozen skeletons used for enzymatic hydrolysis process.

Hydrolysis

Enzymatic hydrolysis was performed using Protamexat a pH of approximately 6.5 and at a temperature of 55±2°C. Protamex(E.C. 3.4.21.62/3.4.24.28) is proteiny complex of Bacillus from Novozymes AS (Bagsvaerd, Denmark) and corresponds to the purity required for food enzymes. The ratio of skeletons salmon and water was 1.14. For hydrolysis used the ratio of enzyme to substrate 11,1 EA/kg crude protein. After 60 is in enzymatic processing temperature was raised to 98°C, which was achieved through 105 minutes

Clean

Large bones were left in the vessel for hydrolysis, and small bones were removed by filtration of the hydrolysate through a sieve. Then the insoluble fraction was removed in a two-phase separator (Westfalia, Germany, SC.35-26-177, 15 kW, 7200 rpm), then the remaining mixture was separated in a phase separator (Westfalia, Germany, SB-7-36-+76, 4 kW, 8520 rpm) on salmon oil, a fraction of the emulsion and the aqueous fraction. The aqueous fraction was concentrated (NitroAtomicer, Denmark, an evaporator falling film, Ff 100), filtered through ultramarino with passport limit of molecular weight 100 000 (system PCI membranes, UK, PF100, 2.65 m2and in the end filtered through ultramarino fraction (fraction UF) was subjected to a spray dryer (Niro Atomizer, Denmark, column P-63, Tinside=200°C Toutside=84°C).

The final product

Fraction UF is called hydrolyzed fish proteins (FPH). The FPH material contains approximately 83% protein, 10% ash and about 2% lipids based on dry weight. Additional features FPH can be found in the earlier application No 2003 3078 applicant. Synthesis of FPH was given as an example and not to illustrate the synthesis of all protein materials or even hydrolysates of fish proteins of the formula (I).

1.2 Getting protein material unicellular organisms (SCP)

Raw materials

Microbial Kul is round, containing Methylococcus capsulatus (Bath), Ralstonia sp., Brevibacillus agri and Aneurinibacillus sp, all commercially available in Norferm Denmark AS, Odense, Denmark received in the loop fermenter continuous fermentation of natural gas in the environment of ammonium salt/mineral salt (AMS) at 45°C, pH 6.5 and at a dilution rate of 0.15 h-1. Liter of medium contained the following components: 10 mg NH3, 75 mg of H3PO4·2H2O, 380 mg MgSO4·7H2O, 100 mg CaCl2·2H2O, 200 mg, K2SO4, 75 mg FeSO4·7H2O, 1.0 mg CuSO4·5H2O 0,96 mg ZnSO4·7H2O, 120 µg CoCl2·6H2O, 48 µg MnCl2·4H2O, 36 ug H3BO3, 24 µg NiCl2·6H2O and 1.20 µg NaMoO4·2H2O.

Getting

The fermenter was filled with water which had been sterilized by heating for 10 seconds at 125°C. Additional dietary supplements are regulated in accordance with their consumption. Continuous fermentation was performed for 2-3% of the biomass (based on dry mass).

Material unicellular organisms received continuously and subjected to centrifugation in an industrial centrifuge continuous operation at 3000 rpm, followed by ultrafiltration using membranes with a limit of 100,000 daltons. Then the resulting product was subjected to sterilization heat exchanger for about 90 seconds at about 130°C.

the additional features of the SSP can be found in the earlier application No 2003 3082 applicant. Synthesis of SSP is given as an example and not to illustrate the synthesis of all protein materials or even protein materials unicellular organisms of the formula (I).

1.3 Fermented protein material is soy

Fermented protein material of soybean was obtained in the fermentation of soy beans. It contains modified and unmodified soy proteins and isoflavones, as well as other components of soy. In the preferred embodiment, this invention uses the fermented protein material is soy Gendaxin®, commercially available in Aximed, Bergen, Norway. Gendaxin® is given as an example and not to illustrate all protein materials or even fermented protein materials soy formula (I).

1.4 Biological effects of the compositions according to this invention in rats

Chemicals

Chemical reagents were obtained from common commercial sources and were of chemically pure. As a control (negative) used carboxymethylcellulose (CMC). Fish oil has been commercially available in Hordafor.

Animals

Male Wistar rats with a weight of from 250 to 358 g was purchased in AnLab Ltd. (Prague, Czech Republic) and were kept in cages made of wire at a temperature of 22±1°C and in a room with controlled lighting (light from 7 until noon to 7 PM). In eating and drinking the E. it. Each cell held three rats. The increase in weight and feed consumption were determined every day.

Diets

Rats were fed a standard Chow diet ST1 (Velaz, Prague, Czech Republic).

Introduction

Before the experiment, male Wistar rats were given the opportunity to adapt to new environmental conditions. Then they spent the introduction of every day for 10 days by feeding through a tube. As the media and the negative control used CMC. In each group on introduction were 4 rats. In groups, which were introduced TTA, was administered 150 mg/kg body weight/day TTA dissolved in CMC or oils. In groups, which were introduced fish oil, was injected 3 ml (approximately 2.5 g)/kg body weight/day. In groups, which were introduced fermented protein material is soy was introduced 0.45 g/kg body weight/day. As the media and the negative control used CMC. On the next day after the last injection the rats were killed.

Killing and removing tissue

Rats were performed under anesthesia with a mixture of 1:1 Hypnorm(fentanyl citrate 0,315 mg/ml and fluanisone 10 mg/ml, Janssen Animal Health) and Dormicum® (midazolam 5 mg/ml, F. Hoffmann-La Roche), injected subcutaneously. Conducted blood directly from the heart using rinsed with heparin syringe. The liver was immediately removed, weighed and divided into two parts, which direct cooling gap is Ali on ice or frozen in liquid nitrogen, respectively. Plasma and tissues were stored at -80°C until analysis. The Protocol was approved by the Management of Norway on biological experiments on living animals.

Getting subcellular liver fractions

Rat liver homogenized separately in ice-cold sucrose solution (0.25 mol/l sucrose, 10 mmol/l HEPES buffer pH 7.4, 1 mmol/l EDTA) using a homogenizer (Potter-Elvehjem. Subcellular fractionation of liver was performed as described previously (Berge RK et al. (1984) Eur J Biochem 141:637-44). The procedure was carried out at 0-4°C, and fractions were stored at -80°C. Protein was evaluated by the test kit BioRad protein using bovine serum albumin as the standard.

Analysis of enzyme

The activity of acyl-CoA-oxidase fat was measured in peroxisomal fraction of the liver as described previously (Small GM, Burdett K, Connock MJ (1985) Biochem J 227: 205-10). The results were reported as the activity of acyl-CoA oxidase fat relative to total protein, subtract the initial activity (activity control)data, which is shown in Fig. 1, normalized relative to the activity of TTA.

Analysis of lipids

The plasma lipids and liver was determined by the enzymatic system Technicon Axon (Miles, close to Tarrytown music hall, NY) using a set of triglycerides from Bayer, for total cholesterol (Bayer, close to Tarrytown music hall, NY) and set PAP 150 for phospholipids containing choline, from bioMerieux. The results presented is s relative to total protein. The results were presented relative to total protein, and the data that is shown in Fig. 2-4, normalized relative to the activity of the positive control (without addition of TTA or oils; i.e. a "normal" level). The results were presented relative to total protein, and the data that is shown in Fig. 2-4, normalized relative to the activity of the positive control (without addition of TTA or oils; i.e. a "normal" level).

Example 2

Biological effects of the compositions of this invention in Atlantic salmon

2.1 Experimental model, including the production of fish feed

Experimental diet based on fish meal was provided EWOS and contained 0.01% of Y2O3as the inert marker for determination of digestibility (3-mm pellets). Table 1 presents the compositions and chemical composition of three types of diets. All three diets were obtained from the same feed mixture. Different diets were obtained by coating conventional feed pellets of different oils and blends. The diets consisted of either fish oil (fat capelin) (control), fish oil with addition of 0.5% TTA (0,5% TTA) or fish oil with addition of 1.5% TTA (1,5% TTA).

The composition of fatty acids in diets clearly reflects that used fish oil (fat capelin) (table 2). Fat is oivi contained relatively high levels of monounsaturated FA and was also enriched in n-3 FA long chain 20:5 n-3 (EPA) and 22:6 n-3 (DHA). Food, however, contained a considerable quantity of fish meal, which contained n-3 FA, enabling higher levels of these FA in the diet than in the added oil.

In addition to the above rations were made identical diets with 0.5% Gendaxin and 0% or 0.9% TTA (based on the total dry weight of feed).

Control: fish oil, from 0.5% TTA: fish oil with addition of 0.5% TTA, a 1.5% TTA: fish oil with addition of 1.5% TTA. The amount of each fatty acid is presented as a percentage of total fatty acids.

2.2: the Cultivation of Atlantic salmon at the stern, containing TTA

Fish, conditions and scheme of the experiment

The test was conducted at the research station AKVAFORSK, Sunndalsora, Norway. Atlantic salmon (Salmon salar) with an average initial weight of approximately 86 g) was placed in a 15 cylindrical conical tanks (diameter of 0.85 m), 40 in the tank. The vessel was filled with sea water with a constant temperature of 12°C. Fish were given the opportunity to adapt to the temperature and fed a commercial feed for two weeks before testing. Test on cultivation consisted of a period of time of 8 weeks.

Rations consisted of rations, as described above in table 2, which contained either fish oil (fat capelin) (control)or fish oil with added the eating of 0.5% TTA (0,5% TTA), either fish oil with addition of 1.5% TTA (1,5% TTA). Three diets was randomly assigned to three tanks. Food was distributed through the electric supply system (Akvaprodukter AS Sunndalsora). Containers are designed in such a way that the excess of food was collected from the waste water in the box from the wire frame. Excess feed was collected, and it was possible to calculate the mass of consumed feed.

A diet that includes Gendaxin used in a separate experiment, but the scheme of the experiment was similar to the pattern described above.

The source and destination sampling

Fish were not fed for 2 days before the original fence images. Six fish from each tank were performed under anesthesia with MS-222 at the beginning and at the end of the experiment and determined the average weight and average length. These six fish were killed by a blow on the head and opened the abdominal cavity. Samples of liver, heart, gills and kidneys were immediately frozen in liquid nitrogen and kept at -80°C. These samples are then used for analysis of fatty acid composition. An additional five fish from each tank were anesthesia and were killed. These fish were used to determine the composition of the whole body.

Before final sampling fish feeding did not stop. Of the five fish from each tank were isolated samples of excreta in accordance with the method described Austreng (Aquaculture, 1978 13:265-72). Before analysis the samples of faeces from each tank were pooled. The samples were stored at -20°C.

The second Gill arch was removed from the fish, which held the anesthesia, and were washed in ice-cold SEI buffer (150 mm sucrose, 10 nm EDTA, 50 mm imidazole, pH 7.3) and immediately frozen in liquid nitrogen. Tissue gills were stored at -80°C. Liver homogenized in ice-cold medium with sucrose.

Growth

Average weight of fish in groups with all diets approximately tripled during the test, the initial value was 86 g to the final value of approximately 250, SGR decreased with increasing doses of TTA in the diet, from SGR a 1.8 in the control group to SGR 1.7 in group c 0.5% TTA and SGR of 1.5 in the group with 1.5% TTA (table 3). Between groups on the diet were not significant differences in the coefficients of fatness (table 3).

Feed intake and digestibility of food additives

In this test revealed only small differences in digestibility (table 4). The digestibility of FA in all groups in the diets was high, more than 96% for the sum of all FA for fish fed the control diet and the diet with 0.5% TTA, and more than 90% for fish fed diet with 1.5% TTA. The digestibility for saturated FA was generally lower than the digestibility of other FA.

For the content of protein, fat and energy of individual fatty acids in the diet of Atlantic salmon, containing Control: fish oil, from 0.5% TTA: fish oil with addition of 0.5% TTA, a 1.5%TTA: fish oil with addition of 1.5% TTA

Data represent mean values ±SEM

Values in the same row with different Superscript characters are significantly different; nd = not determined.

2.3 Biological effects of TTA

Chemicals

Acetic acid, chloroform, petroleum ether and methanol were obtained from Merck (Darmstadt, Germany). Benzene was obtained from Rathburn Chemicals Ltd. (Walkerburn, Scotland) and 2',7'-dichlorofluorescein from Sigma Chemical Co. (St.Louis, MO, USA). A methanolic HCl solution and 2.2-dimethoxypropane acquired Supelco Inc. (Bellfonte, PA, USA). Covered in glass tablets on silica gel K6 received Whatman International Ltd. (Maidstone, UK).

Chemical analysis

In fish samples obtained at the beginning and at the end of the experiment were analyzed by dry residue, fat, protein, ash and energy value. In all the diets and samples of faeces were analyzed dry residue (drying at 105°C to constant weight), fats (extraction with ethyl acetate, as described in NS 9402, 1994), proteins (using Kjeltec Autoanalyser-N*6.25), starch, ash (by heating to 550°C to constant weight), energy and yttrium oxide (using ICP-AES after wet ashing of samples). The energy value of diets, and feces samples of whole fish were determined using an adiabatic the calorimetry in the bomb, using calorimetric bomb Parr 1271.

Extraction of lipids and analysis of fatty acids

Total lipids were extracted from homogenised gills, liver and heart using the method described by Folch (J Biol Chem 1957 226:497-509). Phase chloroform-methanol from the gills was dried in nitrogen atmosphere and dissolved in hexane. Phospholipids (PL), triacylglycerol (TAG) and free fatty acids (FFA) were separated by thin-layer chromatography (TLC) using a mixture of petroleum ether, diethyl ether and acetic acid (113:20:2 by volume) as mobile phase. The lipids were visualized by spraying the TLC plates with 0.2% (wt./about.) 2'7'-dichlorofluorescein in methanol and identified by comparison with known standards under UV-light.

Spots corresponding to PL, FFA and TAG scraped into glass vials and then there was the TRANS-methylation during the night 2,2-dimethoxypropane, methanol-HCL and benzene at room temperature, as described by Mason and Waller (Anal Chem 1964 36:583). Methyl esters were separated mainly on non-polar column with a fused capillary gas chromatography as described Rosjo (Fish Physiol Biochem 1994 13:119-132). FA methyl esters were separated on a gas chromatograph (Perkin-Elmer Auto system GC injector equipped programmable injector split/no split) with column CP wax 52 (length 25 m, internal diameter 0.25 mm and a thickness of the second film of 0.2 μm), a flame ionization detector and data system 1022. The carrier gas was a He, and the temperature of injector and detector was 280°C. the oven Temperature was raised from 50°C to 180°C at a rate of 10°C min-1and then increased to 240°C with a rate of 0.7°C min-1. The relative amount of each presents fatty acids was determined by measuring the peak area corresponding to this acid.

Calculations

The coefficient of apparent digestibility (ADC) was calculated as described Austreng (Aquaculture, 1978 13:265-272). The ratio of fatness (CF), hepatosomatic index (HSI), specific growth factor (SGR) and the growth factor per unit of heat (TGC) was calculated as follows, based on the individual performance of mass and length:

SGR=(e(ln W1-ln W0)/d)-1)·100

TGC=(W11/3-W01/3)·1000/(day·°C)

where W0represents the initial weight, W1is the final mass, t is the temperature during the day.

CF=100·W·(length according to Smith)-3

HSI=100·weight of the liver · W-1

Statistical analysis

All data was performed by one-factor analysis of variance (ANOVA) and differences were ranked according to the criterion of multiple comparisons Duncan. The significance level was set at 5%.

Body composition and liver

Fish fed the diet with 1.5% TTA, possessed b is more low level of lipids in the body (9,6%), than fish fed the control diet (10,6%) (table 5). No statistically significant differences in the total content of lipids between fish fed the control diet and fish fed diet with TTA (table 6). Hepatosomatic index was significantly higher in fish fed diet with 1.5% TTA (1,2%)than in fish fed the control diet (1,1%) (table 6).

Control: fish oil, from 0.5% TTA: fish oil with addition of 0.5% TTA, a 1.5% TTA: fish oil with addition of 1.5% TTA.

abDifferences between average values in this row are significant (p<0,05), as indicated by different Superscript letters.

Results represent mean values ±SEM (n=3). Values in the same row with different Superscript letters are significantly different.

The fatty acid composition of liver, gills and heart

The fatty acid composition of PL, TAG and FFA in the gills, liver and heart are presented in tables 7, 8 and 9. TTA was part of the faction of the PL in the gills (0.8%) and heart (0,7%) Atlantic salmon, which were fed a diet with 1.5% TTA. TTA also included in the composition of the fractions TG and FFA in the gills (table 7). Trace amounts of TTA and its products, obtained under the action of Δ9desaturase, was included in the lipid composition of the liver, while no dedicated product Δ 9desaturase of lipids heart and gills.

The percentage of n-3 FA in the liver, gills and heart was also dependent on diet, which gave the fish. The percentage of EPA+DHA was significantly higher in fish fed diet with 1.5% TTA, than in the control fish, in all the lipid fractions of the gills and heart. In the liver, on the other hand, TTA has only led to a moderate increase of the percentage of DHA and a small decrease in the percentage of EPA. The percentage of palmitic acid (16:0) and the sum of all saturated FA was significantly lower in the PL fraction of the gills, heart and liver of fish fed diet with 1.5% TTA, than in fish fed the control diet (table 7, 8, 9). The sum of all monounsaturated FA was significantly lower in fractions of TG and FFA gills in fish fed a ration of 1.5% TTA, than in fish fed the control diet (table 8). In contrast, the percentage amounts of monounsaturated FA in fractions of PL and TAG liver was higher in fish fed higher doses of TTA (table 9).

2.4 Biological effects of the compositions of this invention, including fermented protein material is soy

Chemicals

Gendaxin received from Aximed, Bergen, Norway. One capsule Gendaxin® contains 35 mg of isoflavones, in addition to 10 mg genistein and 15 mg daidzein.

Analysis of lipids

The plasma lipids were determined enzymatically using system Technicon Axon (Miles, Tarrytown, NY) using a set of triglycerides from Bayer, set for total cholesterol (Bayer, close to Tarrytown music hall, NY) and set PAP 150 for containing choline phospholipids from bioMerieux. The results are presented in mmol/l in table 10.

The data presented above it is clear that adding Gendaxin in forage fish has a positive effect on the fatty acid composition in plasma of salmon. Cholesterol, triglycerides, and phospholipids adding 0.25% of Gendaxin in forage fish were decreased compared to control. Further adding Gendaxin and TTA additionally improved fatty acid composition in plasma.

Analysis of enzymes

The activity of acyl-CoA-oxidase fat was determined in peroxisomal fraction of the liver as described previously (Small GM, Burdett K, Connock MJ (1985) Biochem J 227: 205-10). The results are presented as the activity of acyl-CoA-oxidase fat relative to total protein in table 11.

Table 11
β-oxidation in the liver
Beta-oxidation
Control
0,5% Gendaxin+0,9% TTA
0,940
1,501

The data presented above it is obvious that adding feed for fish Gendaxin and TTA has a positive effect on β-oxidation, since β-oxidation was significantly increased.

Example 3

In accordance with the experimental model presented in example 1, the authors of the present invention conducted an experiment on feeding on male Wistar rats (see table 12) with the following components of the feed:

30% fats

20% protein

5% fibres

10% sucrose

a 3.5% mineral mixture AIN93G

1,0% vitamin mix AIN-93

Else: Starch

Component of fat is 30% pork fat, or 2.5-5% pork fat substituted for fish oil, or 0.15 pork fat replaced by TTA. Protein material is a 20% milk protein (casein), or half of its substituted protein fish or "Bioprotein".

1. Applying a preparation containing a combination of:
1) fermented and/or hydrolyzed protein material, and
2) one or more compounds containing not undergo β-oxidation structural element of a fatty acid represented by
(a) the General formula R-COO-(CH2)2n+1-X-R', where X represents a sulfur atom, a selenium atom is, an oxygen atom, a group of CH2group SO or group SO2; n is a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, where the main chain of the specified R' contains from 13 to 23 carbon atoms and optionally one or more heterogroup selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group and SO the group of SO2; and R" represents a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms; provided that at least one X is not CH2and/or
(b) the General formula (I),

where R1, R2 and R3 represent
(i) a hydrogen atom; or
ii) a group of the formula CO-R, where R is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of the specified R contains from 1 to 25 carbon atoms; or
iii) a group of the formula CO-(CH2)2n+1-X-R', where X represents a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group SO or group SO2; n is a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, where the main chain R' contains from 13 to 23 carbon atoms and optionally one or more heterogroup selected from the group containing an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group and SO the group of SO2;
iv) a structural element selected from the group consisting of-PO3CH2CHNH3COOH (phosphatidylserine), PO3CH2CH2NH3(phosphatidylethanolamine), PO3CH2CH2N(CH2)3(phosphatidylcholine), PO3CH2CHOHCH2OH (phosphatidylglycerol) and RHO3(SNON)6(phosphatidylinositol);
where R1, R2 and R3 are chosen independently from i), ii), iii) or iv), but at least one of R1, R2 or R3 is defined as (iii); provided that at least one X is not CH2and/or
(C) the General formula (II),

where A1, A2 and A3 are chosen independently and represent an oxygen atom, a sulfur atom or a group N-R4, in which R4 represents a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 5 carbon atoms;
where R1, R2 and R3 represent
(i) a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 23 carbon atoms; or
ii) a group of the formula CO-R in which R represents a linear or branched alkyl group, saturated or unsaturated, optionally samewe the ing, and the main chain of the specified R contains from 1 to 25 carbon atoms; or
iii) a group of the formula CO-(CH2)2n+1-X-R', where X represents a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group SO or group SO2; n is a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, where the main chain of the specified R' contains from 13 to 23 carbon atoms and optionally one or more heterogroup selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group and SO the group of SO2;
iv) a structural element selected from the group consisting of-PO3CH2CHNH3COOH (phosphatidylserine), PO3CH2CH2NH3(phosphatidylethanolamine), PO3CH2CH2N(CH2)3(phosphatidylcholine), PO3CH2CHOHCH2OH (phosphatidylglycerol) and RHO3(SNON)6(phosphatidylinositol);
where R1, R2 and R3 are chosen independently from i), ii), iii) or
iv), but at least one of R1, R2 or R3 is defined as
iii); provided that at least one X is not CH2and/or
salt, prodrug or complex compounds according to paragraphs.(a)-(C) to obtain a pharmaceutical or food compositions for the prevention and/or treatment resistance and Sulina, obesity, diabetes, fatty infiltration of the liver, hypercholesterolemia, dyslipidemia, atherosclerosis, coronary heart disease, thrombosis, stenosis, secondary stenosis, myocardial infarction, stroke, elevated blood pressure, endothelial dysfunction, a condition of high blood coagulability, polycystic ovarian syndrome, metabolic syndrome, malignant tumors, inflammatory disorders, and proliferative disorders of the skin.

2. The use according to claim 1, where the specified prevention and/or treatment of a malignant tumor involves inhibition:
primary and secondary tumors, tumor growth, invasion of the primary tumor in the connective tissue and the formation of secondary tumors.

3. The use according to claim 1, where the inflammatory violation is selected from the group consisting of immune disorders such as rheumatoid arthritis, systemic vasculitis, systemic lupus erythematosus, systemic sclerosis, dermatomyositis, polymyositis, various autoimmune endocrine disorders (e.g., thyroiditis and adrenalin), various immune neurological disorders (e.g. multiple sclerosis and myasthenia gravis), various cardiovascular disorders (e.g., myocarditis, congestive heart failure, arteriosclerosis, and stable and unstable angina and pellets is Matos's granulomatosis), inflammatory bowel disease and Crohn's disease, nonspecific colitis, pancreatitis, nephritis, cholestasis/fibrosis of the liver, and acute and chronic graft rejection after organ transplantation, and diseases that have an inflammatory component, such as, for example, Alzheimer's disease or impaired/is able to improve cognitive function.

4. The use according to claim 1, where the specified proliferative disorder skin selected from the group consisting of psoriasis, atopic dermatitis, non-specific dermatitis, primary irritant contact dermatitis, allergic contact dermatitis, lamellar ichthyosis, epidermolizei hyperkeratosis, pre-malignant induced by the action of solar keratosis and seborrhea.

5. The use of animal feed containing common components of the feed and mix:
1) fermented and/or hydrolyzed protein material, and
2) one or more compounds containing not undergo β-oxidation of structural elements fatty acids, presents
(a) the General formula R-COO-(CH2)2n+1-X-R', where X represents a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group SO or group SO2; n is a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or nanosys is nnow, optionally substituted, where the main chain of the specified R' contains from 13 to 23 carbon atoms and optionally one or more heterogroup selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group and SO the group of SO2; and R" represents a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms; provided that at least one X is not CH2and/or
(b) the General formula (I),

where R1, R2 and R3 represent
(i) a hydrogen atom; or
ii) a group of the formula CO-R, where R is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of the specified R contains from 1 to 25 carbon atoms; or
iii) a group of the formula CO-(CH2)2n+1-X-R', where X represents a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group SO or group SO2; n is a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, where the main chain of the specified R' contains from 13 to 23 carbon atoms and optionally one or more heterogroup selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2that group is SO and a group of SO 2;
iv) a structural element selected from the group consisting of-PO3CH2CHNH3COOH (phosphatidylserine), PO3CH2CH2NH3(phosphatidylethanolamine), PO3CH2CH2N(CH2)3(phosphatidylcholine), PO3CH2CHOHCH2OH (phosphatidylglycerol) and RHO3(SNON)6(phosphatidylinositol);
where R1, R2 and R3 are chosen independently from i), ii), iii) or iv), but at least one of R1, R2 or R3 is defined as (iii); provided that at least one X is not CH2and/or
(C) the General formula (II),

where A1, A2 and A3 are chosen independently and represent an oxygen atom, a sulfur atom or a group N-R4, in which R4 represents a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 5 carbon atoms;
where R1, R2 and R3 represent
(i) a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 23 carbon atoms; or
ii) a group of the formula CO-R, where R is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of the specified R contains from 1 to 25 carbon atoms; or
iii) a group of the formula CO-(CH2)2n+1--R', where X represents a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group SO or group SO2; n is a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, where the main chain of the specified R' contains from 13 to 23 carbon atoms and optionally one or more heterogroup selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group and SO the group of SO2;
iv) a structural element selected from the group consisting of-PO3CH2CHNH3COOH (phosphatidylserine), PO3CH2CH2NH3(phosphatidylethanolamine), PO3CH2CH2N(CH2)3(phosphatidylcholine), PO3CH2CHOHCH2OH (phosphatidylglycerol) and RHO3(SNON)6(phosphatidylinositol);
where R1, R2 and R3 are chosen independently from i), ii), iii) or iv), but at least one of R1, R2 or R3 is defined as (iii); provided that at least one X is not CH2and/or
salt, prodrug or complex compounds according to paragraphs.(a)-(C) to improve the overall composition of lipids in the body of the animal.

6. The use according to claim 5, where the improvement of the overall composition of lipids involves reducing the overall level of lipids in the body.

7. The use according to claim 5, where the improvement of the General is on lipid composition includes a decrease in the total level of saturated fatty acids in the body.

8. The use according to claim 5, where the improvement of the overall composition of lipids includes the increase in the total level of n-3 fatty acids in the body.

9. The use according to claim 1, where the specified protein material is a protein material unicellular organisms (SCP).

10. The use according to claim 1, where the specified protein material is a hydrolyzed fish proteins.

11. The use according to claim 1, where the specified protein material is a fermented protein material is soy.

12. The application of claim 11, where the specified protein material is soy is a Gendaxin®.

13. The use according to claim 1, where the compound(I)containing not undergo β-oxidation structural element fatty acids is not exposed to β-oxidation of fatty acid.

14. The application indicated in paragraph 13 where the compound(I)containing not undergo β-oxidation structural component of the fatty acid is tetradecylthioacetic acid (TTA), tetrazacyclooctane acid and/or 3-thia-15-heptadecan.

15. The use according to claim 1, where X represents a sulfur atom or a selenium atom.

16. The use according to claim 1, where the compound(I)containing not undergo β-oxidation structural element fatty acids, is a phospholipid, where the specified phospholipid selected from the group consisting of phosphatidylserine, phosphatidylcholine, phosphatide is ethanolamine, phosphatidylinositol, phosphatidylglycerol and/or diphosphatidylglycerol.

17. The use according to claim 1, where the compound containing not undergo β-oxidation structural element fatty acid, is a derivative of phosphatidylcholine 1,2-ditetradecyl-sn-glycero-3-phosphocholine.

18. The use according to claim 1, where the compound containing not undergo β-oxidation structural element fatty acid, is a derivative of phosphatidylethanolamine 1,2-ditetradecyl-sn-glycero-3-phosphoethanolamine.

19. The use according to claim 1, where the compound(I)containing not undergo β-oxidation structural component of the fatty acid is a mono-, di - or triacylglyceride.

20. The application of claim 19 where the compound(I)containing not undergo β-oxidation structural element fatty acids, is triacylglyceride containing tetradecylthioacetic acid (TTA).

21. The use according to claim 1, where the composition further comprises a vegetable and/or fish oil.

22. Use item 21, where vegetable or fish oil contains polyunsaturated fatty acids.

23. The application of article 22, where the vegetable oil is selected from the group consisting of sunflower oil, soybean oil and olive oil.

24. The use according to claim 1, where the specified composition is injected or give food to the animal.

25. When is the change in paragraph 24, where a specified animal is a human.

26. The application of paragraph 24, where the specified animal is an agricultural animal, such as chicken, mammals, related to cattle, sheep, goats or pigs.

27. The application of paragraph 24, where the specified animal is a pet or a pet such as a dog or cat.

28. The application of paragraph 24, where the specified animal is a fish or shellfish such as salmon, cod, tilapia, clams, oysters, lobster or crabs.

29. The use according to claim 1, where the daily dose of the compounds containing not undergo β-oxidation of structural elements fatty acids is about 1-200 mg/kg, preferably 5-50 mg/kg for human consumption, and about 1-2000 mg/kg, preferably 5-500 mg/kg, for consumption by animals.

30. The use according to claim 1, where the daily dose of protein material is about 5-500 mg/kg, preferably 50-300 mg/kg for human consumption and from 5 mg/kg up to a total per diem of protein for consumption by animals.

31. Use item 21, where the daily dose of the oil is approximately 1-300 mg/kg, preferably 10-150 mg/kg for human consumption and from 1 mg/kg up to a total per diem of fats for consumption by animals.

32. The use according to claim 5, where the pet food may be a food composition, a veterinary composition and/or functional food product.

33. Composition for prevention and/or treatment of insulin resistance, obesity, diabetes, fatty infiltration of the liver, hypercholesterolemia, dyslipidemia, atherosclerosis, coronary heart disease, thrombosis, stenosis, secondary stenosis, myocardial infarction, stroke, elevated blood pressure, endothelial dysfunction, a condition of high blood coagulability, polycystic ovarian syndrome, metabolic syndrome, malignant tumors, inflammatory disorders, and proliferative disorders of the skin, characterized in that the said composition comprises the combination of:
1) fermented and/or hydrolyzed protein material, and
2) one or more compounds containing not undergo β-oxidation of structural elements fatty acids, presents
(a) the General formula R-COO-(CH2)2n+1-X-R', where X represents a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group SO or group SO2; n is a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, where the main chain of the specified R' contains from 13 on the 23 carbon atoms and optionally one or more heterogroup, selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group and SO the group of SO2; and R" represents a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms; provided that at least one X is not CH2and/or
(b) the General formula (I),

where R1, R2 and R3 represent
(i) a hydrogen atom; or
ii) a group of the formula CO-R, where R is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of the specified R contains from 1 to 25 carbon atoms; or
iii) a group of the formula CO-(CH2)2n+1-X-R', where X represents a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group SO or group SO2; n is a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, where the main chain of the specified R' contains from 13 to 23 carbon atoms and optionally one or more heterogroup selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group and SO the group of SO2;
iv) a structural element selected from the group consisting of-PO3CH2CHNH3COOH (phosphatidylserine), PO3CH 2CH2NH3(phosphatidylethanolamine), PO3CH2CH2N(CH2)3(phosphatidylcholine), PO3CH2CHOHCH2OH (phosphatidylglycerol) and RHO3(SNON)6(phosphatidylinositol);
where R1, R2 and R3 are chosen independently from i), ii), iii) or iv), but at least one of R1, R2 or R3 is defined as (iii); provided that at least one X is not CH2and/or
(C) the General formula (II),

where A1, A2 and A3 are chosen independently and represent an oxygen atom, a sulfur atom or a group N-R4, in which R4 represents a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 5 carbon atoms;
where R1, R2 and R3 represent
(i) a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 23 carbon atoms; or
ii) a group of the formula CO-R in which R represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of the specified R contains from 1 to 25 carbon atoms; or
iii) a group of the formula CO-(CH2)2n+1-X-R', where X represents a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group SO or group SO2; n Pres who represents a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, where the main chain of the specified R' contains from 13 to 23 carbon atoms and optionally one or more heterogroup selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group and SO the group of SO2;
iv) a structural element selected from the group consisting of-PO3CH2CHNH3COOH (phosphatidylserine), PO3CH2CH2NH3(phosphatidylethanolamine), PO3CH2CH2N(CH2)3(phosphatidylcholine), PO3CH2CHOHCH2OH (phosphatidylglycerol) and RHO3(SNON)6(phosphatidylinositol);
where R1, R2 and R3 are chosen independently from i), ii), iii) or iv), but at least one of R1, R2 or R3 is defined as (iii); provided that at least one X is not CH2and/or
salt, prodrug or complex compounds according to paragraphs.(a)-(C).

34. The composition according to p in which the specified protein material is a protein material unicellular organisms (SCP).

35. The composition according to p in which the specified protein material is a hydrolyzed fish proteins.

36. The composition according to p in which the specified protein material is a fermented protein material is soy.

37 Composition on p, in which the specified protein material is soy is a Gendaxin®.

38. The composition according to p, where the composition comprises a daily dose of the compounds containing not exposed to β-oxidation similar fatty acid, about 1-200 mg/kg, preferably 5-50 mg/kg for human consumption and about 1-2000 mg/kg, preferably 5-500 mg/kg, for consumption by animals.

39. The composition according to p, where the composition further comprises a vegetable and/or fish oil.

40. The composition according to p, where the compound(I)containing not undergo β-oxidation structural element fatty acids, is not exposed to β-oxidation of fatty acid.

41. The composition according to p, where the compound(I)containing not undergo β-oxidation structural element fatty acids, is tetradecylthioacetic acid (TTA), tetrazacyclooctane acid and/or 3-thia-15-heptadecan.

42. The composition according to p, where X represents a sulfur atom or a selenium atom.

43. The composition according to p, where the compound(I)containing not undergo β-oxidation structural element fatty acids, is a phospholipid, where the specified phospholipid selected from the group consisting of phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol, and/or diphosphatidylglycerol.

44. Compo is ice on p, where the compound containing not undergo β-oxidation structural element fatty acid, is a derivative of phosphatidylcholine 1,2-ditetradecyl-sn-glycero-3-phosphocholine.

45. The composition according to p, where the compound containing not undergo β-oxidation structural element fatty acid, is a derivative of phosphatidylethanolamine 1,2-ditetradecyl-sn-glycero-3-phosphoethanolamine.

46. The composition according to p, where the compound(I)containing not undergo β-oxidation structural component of the fatty acid is a mono-, di - or triacylglyceride.

47. The composition according to item 46, where the compound(I)containing not undergo β-oxidation structural component of the fatty acid is triacylglyceride containing tetradecylthioacetic acid (TTA).

48. The composition according to p, where vegetable or fish oil contains polyunsaturated fatty acids.

49. The composition according to p, where vegetable oil is selected from the group consisting of sunflower oil, soybean oil and olive oil.

50. The composition according to p, where the composition comprises a daily dose of protein material about 5-500 mg/kg, preferably 50-300 mg/kg for human consumption and from 5 mg/kg up to a total per diem of protein for consumption by animals.

51. The composition according to p where compositiontarget daily dose of oil approximately 1-300 mg/kg, preferably 10-150 mg/kg for human consumption and from 1 mg/kg up to a total per diem of fats for consumption by animals.

52. The composition according to p, where the composition is an animal feed additionally contains conventional components of the feed.

53. The composition according to p, where animal feed is a feed for fish.

54. The composition according to p, where food for fish is a food for salmon.

55. The composition according to p, where common components of the feed containing fishmeal and/or fish oil.

56. A method of obtaining a product of animal origin with the improved composition of fatty acids, comprising feeding the animal intended to obtain a product, animal feed, containing common components of the feed and mix:
1) fermented and/or hydrolyzed protein material, and
2) one or more compounds containing not undergo β-oxidation of structural elements fatty acids displayed
(a) the General formula R-COO-(CH2)2n+1-X-R', where X represents a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group SO or group SO2; n is a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, where the main t the universi specified R' contains from 13 to 23 carbon atoms and optionally one or more heterogroup, selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group and SO the group of SO2; and R" represents a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms; provided that at least one X is not CH2and/or
(b) the General formula (I),

where R1, R2 and R3 represent
(i) a hydrogen atom; or
ii) a group of the formula CO-R, where R is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of the specified R contains from 1 to 25 carbon atoms; or
iii) a group of the formula CO-(CH2)2n+1-X-R', where X represents a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group SO or group SO2; n is a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, where the main chain of the specified R' contains from 13 to 23 carbon atoms and optionally one or more heterogroup selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group and SO the group of SO2;
iv) a structural element selected from the group consisting of-PO3CH2CHNH3COOH (phosphatidylserine), PO3CH 2CH2NH3(phosphatidylethanolamine), PO3CH2CH2N(CH2)3(phosphatidylcholine), PO3CH2CHOHCH2OH (phosphatidylglycerol) and RHO3(SNON)6(phosphatidylinositol);
where R1, R2 and R3 are chosen independently from i), ii), iii) or iv), but at least one of R1, R2 or R3 is defined as (iii); provided that at least one X is not CH2and/or
(C) the General formula (II),

where A1, A2 and A3 are chosen independently and represent an oxygen atom, a sulfur atom or a group N-R4, in which R4 represents a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 5 carbon atoms;
where R1, R2 and R3 represent
(i) a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 23 carbon atoms; or
ii) a group of the formula CO-R in which R represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of the specified R contains from 1 to 25 carbon atoms; or
iii) a group of the formula CO-(CH2)2n+1-X-R', where X represents a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group SO or group SO2; n PR is dstanley a number from 0 to 11; and R' represents a linear or branched alkyl group, saturated or unsaturated, optionally substituted, where the main chain of the specified R' contains from 13 to 23 carbon atoms and optionally one or more heterogroup selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a group of CH2group and SO the group of SO2;
iv) a structural element selected from the group consisting of-PO3CH2CHNH3COOH (phosphatidylserine), PO3CH2CH2NH3(phosphatidylethanolamine), PO3CH2CH2N(CH2)3(phosphatidylcholine), PO3CH2CHOHCH2OH (phosphatidylglycerol) and RHO3(SNON)6(phosphatidylinositol); where R1, R2 and R3 are chosen independently from i), ii), iii) or
iv), but at least one of R1, R2 or R3 is defined as
iii); provided that at least one X is not CH2and/or
salt, prodrug or complex compounds according to paragraphs.(a)-(C).

57. The method according to p, where the product of animal origin is a meat product.

58. The method according to p, where the product of animal origin is a product of oil-based.

59. The method according to p, where the product of animal origin is a product based on the skin.

60. The drug containing a combination of:
1) mA protein is Arial and
2) vegetable oil or fish oil, in which the protein material selected from the group comprising proteins of unicellular organisms (SCP), hydrolyzed fish proteins, fermented protein material is soy, preferably Gendaxin®, to obtain a pharmaceutical or nutritional composition for the prevention and/or treatment of hypercholesterolemia and conditions, which negatively affected by high cholesterol levels, insulin resistance, obesity, diabetes, fatty infiltration of the liver, dyslipidemia, atherosclerosis, coronary heart disease, thrombosis, stenosis, secondary stenosis, myocardial infarction, stroke, elevated blood pressure, endothelial dysfunction, status, increased blood clotting, polycystic ovarian syndrome, metabolic syndrome, malignant tumors, inflammatory disorders, and proliferative skin disorders.

61. Use p, where vegetable oil or fish oil contains polyunsaturated fatty acids.

62. Use p, where vegetable oil is selected from the group consisting of sunflower oil, soybean oil and olive oil.

63. Use p where indicated prevention and/or treatment of a malignant tumor involves inhibition:
primary and secondary tumors, tumor growth, invasion of the primary tumor in edentulous tissue and the formation of secondary tumors.

64. Use p, where inflammatory violation is selected from the group consisting of immune disorders such as rheumatoid arthritis, systemic vasculitis, systemic lupus erythematosus, systemic sclerosis, dermatomyositis, polymyositis, various autoimmune endocrine disorders (e.g., thyroiditis and adrenalin), various immune neurological disorders (e.g. multiple sclerosis and myasthenia gravis), various cardiovascular disorders (e.g., myocarditis, congestive heart failure, arteriosclerosis, and stable and unstable angina and Wegener's granulomatosis), inflammatory bowel disease and Crohn's disease, nonspecific colitis, pancreatitis, nephritis, cholestasis/liver fibrosis, and acute and chronic graft rejection after organ transplantation, and diseases that have an inflammatory component, such as, for example, Alzheimer's disease or impaired/is able to improve cognitive function.

65. Use p, where the specified proliferative disorder skin selected from the group consisting of psoriasis, atopic dermatitis, non-specific dermatitis, primary irritant contact dermatitis, allergic contact dermatitis, lamellar ichthyosis, epidermolizei hyperkeratosis, induced pre-malignant dei is the influence of solar keratosis and seborrhea.

66. The use according to any one of p-65, where the specified composition is injected or give food to the animal.

67. Use p where a specified animal is a human.

68. Use p where a specified animal is an agricultural animal, such as chicken, mammals, related to cattle, sheep, goats or pigs.

69. Use p where a specified animal is a pet or a pet such as a dog or cat.

70. Use p where a specified animal is a fish or shellfish such as salmon, cod, tilapia, clams, oysters, lobster or crabs.

71. Use p, where the daily dose of protein material is about 5-500 mg/kg, preferably 50-300 mg/kg for human consumption, and from 5 mg/kg up to a total per diem of protein for consumption by animals.

72. Use p, where the daily dose of the oil is approximately 1-300 mg/kg, preferably 10-150 mg/kg for human consumption and from 1 mg/kg up to a total per diem of fats for consumption by animals.

73. Use p where pet food may be a food composition, veterinary composition, and/or functional food product.

74. Composition for pros who ACTICE and/or treatment of hypercholesterolemia and conditions which is negatively affected by high cholesterol levels, insulin resistance, obesity, diabetes, fatty infiltration of the liver, dyslipidemia, atherosclerosis, coronary heart disease, thrombosis, stenosis, secondary stenosis, myocardial infarction, stroke, elevated blood pressure, endothelial dysfunction, a condition of high blood coagulability, polycystic ovarian syndrome, metabolic syndrome, malignant tumors, inflammatory disorders, and proliferative disorders of the skin, containing a combination of:
1) a protein material and
2) vegetable oil or fish oil, in which the protein material selected from the group comprising proteins of unicellular organisms (SCP), hydrolyzed fish proteins, fermented protein material is soy, preferably Gendaxin®.

75. The composition according to p, where vegetable oil or fish oil contains polyunsaturated fatty acids.

76. The composition according to p, where vegetable oil is selected from the group consisting of sunflower oil, soybean oil and olive oil.

77. The composition according to p, where the composition comprises a daily dose of protein material about 5-500 mg/kg, preferably 50-300 mg/kg for human consumption and from 5 mg/kg up to a total per diem of protein for consumption by animals.

78. The composition according to p, where the composition which contains the daily dose of oil approximately 1-300 mg/kg, preferably 10-150 mg/kg for human consumption and from 1 mg/kg up to a total per diem of fats for consumption by animals.

79. The composition according to p, where the composition is an animal feed additionally contains conventional components of the feed.

80. The composition according to p, where animal feed is a feed for fish.

81. The composition according to p, where food for fish is a food for salmon.

82. The composition according to p, where common components of the feed containing fishmeal and/or fish oil.



 

Same patents:

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to hematology, cardiology, endocrinology, and can be applied for normalisation of microvesicle level in blood in case of glucose tolerance disturbance. For this purpose introduced is pioglitazone 30 mg 1 time in the morning and dosed physical loadings are prescribed. Duration of treatment is not less than 6 weeks.

EFFECT: method results in normalisation of microvesicle level in blood of patients of said category, reducingmanifestations, including, endothelial dysfunction, as well as considerably reducing hemocoagulation potential of blood, reducing risk of thrombotic complications.

1 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to cardiology, and deals with normalisation of functional reactivity of cardio-vascular system (CVS) in case of crisis course of arterial hypertension with disturbance of glucose tolerance. For this purpose estimation of CVS functional reactivity state under psychoemotional load is carried out by registration of systolic diastolic everage dynamic pressure (APav.dyn.) and heart rate (HR). On the basis of obtained data functional reactivity index (FRI) is determined before and after load, using the formula: FRI= APav.dyn.x HR)100 (conv. units). If FRI value after load increases on more than 20 conv.units, treatment including irbersartan 150 mg in the morning 1 time and lacidipine 4 mg in the morning 1 time during not less than 2 months.

EFFECT: such complex of medicamentary therapy in combination with empirically selected treatment duration ensures normalisation of CVS functional reactivity in said group of patients due to potentiation of therapeutic effect of applied medications.

1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to haematology, cardiology, endocrinology, and can be used for decreasing the blood microvesicle concentration in the patients with arterial hypertension and impaired glucose tolerance. That is ensured by administration of Valsartan 80 mg once in the morning, Pioglitazone 30 mg once in the morning and prescribed graduated physical activity.

EFFECT: invention provides normalisation of the blood microvesicle level in the case patients that allows considerably lowering hemocoagulation potential of blood, reducing risk of thrombotic complications.

1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to haematology, cardiology, endocrinology, and can be used for correction of the blood microvesicle level in the patients with arterial hypertension and abdominal obesity. That is ensured by administration of Valsartan 80 mg once in the morning, Metformin 500 mg twice a day, and graduated physical activity. The length of treatment is at least 5 weeks.

EFFECT: invention provides normalisation of the blood microvesicle level in the case patients that allows considerably lowering hemocoagulation potential of blood, reducing risk of thrombotic complications.

1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to haematology, cardiology and endocrinology, and can be used for correction of the blood microvesicle level in the patients with dyslipidemia and abdominal obesity. That is ensured by individual hypocaloric diet, graduated physical activity and administration of preparation Lovastatin 40 mg once a day in the evening at mealtimes. The length of treatment is at least 10 weeks.

EFFECT: invention provides normalisation of the blood microvesicle level in the case patients that allows considerably lowering hemocoagulation potential of blood, reducing risk of thrombotic complications.

1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, namely to cardiology and endocrinology, and concerns optimisation of thromboplastin formation activity in the patients with arterial hypertension and impaired glucose tolerance. That is ensured by the integrated treatment including graduated static and dynamic physical activity, daily swimming in a pool for at least 20 minutes, and introduction of metformin in dosage 500 mg 2 times a day and lisinopril in dosage 10 mg once a day in the morning for 1 month.

EFFECT: complex of specific medicines and physical activity combined with empirically prescribed length of treatment provides normalisation of thromboplastin formation that in turn reduces risk of thrombotic complications in the case patients.

1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to cardiology, and concerns optimising the functional responsiveness of the cardiovascular system in arterial hypertension, dislipidemia and abdominal obesity in elderly and senile patients. That is ensured by estimating the condition of functional responsiveness of the CVS in psychoemotional load by recording systolic, diastolic, average dynamic pressure (BPav.dyn.) and heart rate (HR). These data are used to evaluate a functional responsiveness index (FRI) before and after load by formula: FRI=(BPav.dyn. x HR)100 (standard units). The post-load PFR increased more than by 20 standard units requires the integrated treatment including individually prescribed hypocaloric diet calculated by formula considering sex, age and body weight, swimming, morning hygienic gymnastics and therapeutic exercises throughout the day, divided physical activity throughout the day, and administration of irbesartan 150 mg for at least 3 months.

EFFECT: integrated drug-induced and drug-free therapy combined with empirically prescribed length of treatment provides optimisation of functional responsiveness of the CVS in the given group of patients due to potentiation of therapeutic effect of separate components of an individual care.

2 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to haematology and endocrinology, and concerns normalisation of thrombocyte sensitivity to aggregation inducing factors in the patients with arterial hypertension and impaired glucose tolerance. That is ensured by the integrated treatment including graduated physical activity, including daily swimming in a pool for at least 20 minutes a day, and administration of lisinopril in dosage 10 mg once a day in the morning and metformin in dosage 500 mg once a day. The therapeutic course is at least 5 weeks.

EFFECT: complex of specific medical products and physical activity combined with empirically prescribed length of treatment provides complete normalisation of thrombocyte sensitivity to aggregation inducing factors that in turn reduces risk of thrombolytic complications in the given group of patients.

1 ex, 3 dwg, 2 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to haematology and cardiology, and concerns decreasing microvesicles in blood in crisis course of arterial hypertension. That is ensured by administration of Irbesartan in dosage 150 mg once in the morning and Nebivolol in dosage 2.5 mg once in the morning for at least 7 weeks.

EFFECT: method ensures normalised blood concentration of microvesicles that in turn allows reducing risk of thrombotic complications in said group of patients.

1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to cardiology, and concerns normalising the functional responsiveness of cardiovascular system in elderly and senile patients suffering arterial hypertension and metabolic syndrom. That is ensured by estimating the condition of functional reactivity of the CVS in psychoemotional load by recording systolic, diastolic, average dynamic pressure (BPav.dyn.) and heart rate (HR). These data are used to evaluate a functional responsiveness index (FRI) before and after load by formula: FRI=(BPav.dyn. x HR)100 (standard units). The value PFR increased more than by 20 standard units requires the complex therapy including individually prescribed hypocaloric diet calculated by formula considering sex and age and body weight, graduated static and dynamic physical activity, and introduction of irbesartan in dosage 150 mg once in the morning, and pioglitazone in dosage 30 mg once in the morning at least for 3 months.

EFFECT: complex drug-induced and drug-free therapy combined with empirically prescribed treatment length provides normalisation of functional responsiveness of the CVS in the given group of patients due to potentiation of therapeutic effect of separate components of an individual care.

2 ex

FIELD: medicine.

SUBSTANCE: invention relates to pharmaceutical industry, in particular to medication, possessing hypocholesterolemic, hypolipidemic and cholagogic action. Medication possessing hypocholesterolemic, hypolipidemic and cholagogic activity, containing concentrate of triterpene acids, obtained from grist of sea-buckthorn berries by triple extraction with methyl-tret-butyl ether, further purification from non-polar admixtures by washing with petroleum ether, removal of residual amounts of polar compounds by extraction with hot water with simultaneous distillation with water vapour of petroleum ether under definite conditions.

EFFECT: claimed medication possesses efficient hypocholesterolemic, hypolipidemic and cholagogic action, is characterised by low content of strong acids (malic, oxalic, tartaric, citric) and does not possess irritating activity.

1 cl, 3 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: declared invention refers to chemical-pharmaceutical industry, and concerns an emulsion of perfluororganic compounds (PFOC) for medicine and biology, containing mixed perfluorocarbons (PFC) with a main ingredient being perfluorodecahydronaphthalene (PFD) and mixed perfluorochemical tertiary amines (PFTA) with a main ingredient being perfluoro-N-(4-methylcyclohexyl)-piperidine (PFMCP), having smaller excretion rates than PFD, a stabilising agent and a physiologically acceptable water-salt solution with energy metabolism substrata, differing that all the ingredients of PFOS have critical hexane solution temperatures (TcrH), differing no more than by 2-4°C, and the stabilising agent represents mixed block copolymers from the group of block copolymers polyoxyethylene-polyoxypropylene with an average weight content of polyoxypropylene 20%. The invention also concerns a method for making said emulsion, and a method of treating with applying the declared emulsion.

EFFECT: prepared emulsions show high stability and are non-toxic.

21 cl, 5 tbl, 17 ex, 2 dwg

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to vascular surgery, and can be used in treating chronic obliterating diseases of lower extremity arteries. That is ensured by introduction of thrombocyte-enriched autoplasma containing polypeptide growth factors into an involved extremity. Said introduction is ultrasound aided from two points in inguinal and popliteal regions in amount 100 ml for each with distributing along the deep artery of thigh and popliteal artery and in adjacent muscles.

EFFECT: method allows stimulating development of collateral blood flow in an ischemic limb and improving arterial inflow from proximal to distal regions.

1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to therapy and cardiology, and concerns correction of lipidosis and lipid peroxidation. That is ensured by single introduction of Licopin in daily dosage 10 mg every night at bedtime.

EFFECT: method provides normalised cholesterol and lipid peroxidation levels with decreased dose and frequency of preparation administration due to considering circadian rhythm of lipid exchange.

FIELD: chemistry.

SUBSTANCE: claimed compounds show effect on receptor activated by peroxysome proliferate δ (PPARδ). In formula I: [Formula I] , [Formula VII] , [Formula VI] , A is R1 is C1-4alkyl group; R3 groups are different and denote halogen atom or C1-4alkyl group substituted or unsubstituted by halogen; R4 is R5 is hydrogen atom or hydroxyl group; the other radicals are as defined in the invention claim. Also invention refers to methods of compound I obtainment, to intermediary compounds VI, VII and methods of their obtainment, to medicines of diabetes, obesity, atherosclerosis, hyperlipidemia treatment and prevention, containing thiazole derivative of the formula I as active component.

EFFECT: enhanced activity of derivatives.

21 cl, 10 tbl, 102 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to cyclic derivatives of aminobenzoic acid and to their pharmaceutically acceptable salts of general formula , in which ring Ar is a phenyl group, a 5-member aromatic heterocyclic group containing 1-2 heteroatoms selected from nitrogen, sulphur and oxygen, or a benzothiazolyl group; where the said groups can have 1-2 substitutes selected from a group comprising lower alkyl; a phenyl group; a phenyl group substituted with 1-2 halogens; a phenyl group substituted with a lower alkoxy group; a phenyl group substituted with a halogen-substituted lower alkyl group; a phenoxy group substituted with a halogen; a halogen; Z is an oxygen atom or -(CH2)-n (where n equals 0, 1 or 2); Y is C1-C4 alkylene, C2-C4 alkenylene or general formula (2) -T-A-U- (2) in which T is a single bond, C1-C4 alkylene or C2-C4 alkenylene; U is single bond, C1-C4 alkylene; values of the rest of radicals are given in the formula of invention.

EFFECT: obtaining a PPARα, agonist which contains an active ingredient in form of at least one cyclic derivative of aminobenzoic acid, and an agent which reduces the level of lipids which contains an active ingredient in form of at least one cyclic derivative of aminobenzoic acid.

12 cl, 16 tbl, 184 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to cardiology and concerns normalising functional reactivity of cardiovascular system (CVS) in stenocardia function classes I-II. That is ensured by estimating the condition of functional reactivity of the CVS in psychoemotional load by recording systolic, diastolic, average dynamic pressure. These data are used to evaluate a functional responsiveness index (FRI) before and after stress by formula: FRI=(BPav.dyn. x HR)/100 (standard units). The PFR gain by more than 20 standard units requires administration of lisinopril in a dose 5 mg a day in the morning and metoprolol in a dose 50 mg a day in the morning.

EFFECT: method provides normalising functional reactance of cardiovascular system and higher psychoemotional load tolerance in the given group of patients within two-month therapeutic course.

3 ex

FIELD: medicine.

SUBSTANCE: invention concerns a composition obtained from a combination of vegetable oil or cod-liver oil with a compound which contains fatty acids analogues resistant to β-oxidation. The invention also concerns animals' fodder produced form a combination of vegetable oil and cod-liver oil containing fatty acids analogues resistant to β-oxidation, to application of the fodder with the purpose of improving the animal's body composition and to the product obtained from the above animals.

EFFECT: production of pharmaceutical or edible composition for prevention and/or treatment of insulin resistance, obesity, diabetes, fatty liver, hypercholesterinemia, dislipidemia, atherosclerosis, coronary heart disease, thrombosis, stenosis, myocardial infarction, apoplexy, hypertension, endothelial dysfunction, hypercoagulability, polycystic ovary syndrome, metabolic syndrome, malignant tumour, inflammatory disorder and poliferous skin lesions.

47 cl, 12 tbl, 2 ex, 4 dwg

FIELD: medicine.

SUBSTANCE: method is proposed for preventing or slowing down development of atherosclerosis. It involves administration of molsidomine or a pharmaceutically acceptable salt thereof in the form of solid peroral composition with prolonged release of the active substance, effective for 24 hours and containing 14 to 24 mg of molsidomine. The composition is to be administered for at least 6 months.

EFFECT: method significantly decreases level of circulating ICAM-1s (an anti-inflammatory marker of endothelium dysfunction and therapeutic target at atherosclerosis pathological conditions) which play an important role in emergence and development of atherosclerosis.

6 cl, 2 dwg, 2 tbl

FIELD: medicine.

SUBSTANCE: treatment of the patients with chronic heart disease and obliterating atherosclerosis of lower limb is ensured by a course of plasmapheresis consisting of 5-6 sessions every 3-5 days. Each session starts with introduction of 50-60 ml of physiologic saline and removal of 300 ml to 900-1200 ml of plasma prepared by centrifugation in a cold centrifuge at rotary speed 1500-1800 rpm and temperature +4 ° - + 6°C within 15-20 minutes. Plasma is compensated with physiologic saline at the ratio 1:1. The course involves gradual increase of the volume of removed plasma starting with the minimal amount in the first session to the maximal amount to the middle and following decrease of this volume to minimum by the end. Total amount of removed plasma is 1-1.5 volumes of circulating plasma.

EFFECT: method allows administering out-patient continuous treatment of said group of the patients, including in case of resistance to drug therapy.

4 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention relates to pharmaceutical industry, in particular to medication, possessing hypocholesterolemic, hypolipidemic and cholagogic action. Medication possessing hypocholesterolemic, hypolipidemic and cholagogic activity, containing concentrate of triterpene acids, obtained from grist of sea-buckthorn berries by triple extraction with methyl-tret-butyl ether, further purification from non-polar admixtures by washing with petroleum ether, removal of residual amounts of polar compounds by extraction with hot water with simultaneous distillation with water vapour of petroleum ether under definite conditions.

EFFECT: claimed medication possesses efficient hypocholesterolemic, hypolipidemic and cholagogic action, is characterised by low content of strong acids (malic, oxalic, tartaric, citric) and does not possess irritating activity.

1 cl, 3 tbl, 1 ex

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