RU2394598C2 - Composition containing protein material and compounds which contain unoxidisable structural elements of fatty acids - Google Patents

Abstract

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

Description

FIELD OF THE INVENTION

It was shown that by using a combination of non-β-oxidizing structural elements of fatty acids and protein material, unexpected synergistic effects are achieved. The present invention relates to a composition obtained by combining compounds containing non-β-oxidizing fatty acid structural elements and protein material, and to using said composition for the manufacture of a pharmaceutical or food composition for the prevention and / or treatment of insulin resistance, obesity, diabetes, fatty liver infiltration, hypercholesterolemia, dyslipidemia, atherosclerosis, coronary heart disease, thrombosis, stenosis, secondary stenosis, myocardial infarction, stroke, increased blood pressure, endothelial dysfunction, hypercoagulable state, polycystic ovary syndrome, metabolic syndrome, cancer, inflammatory disorders, and proliferative skin disorders. The specified composition can also be used as an additional component in the feed for daily feeding of animals in order to influence the composition of the tissues of their body in general, specifically the composition of fatty acids.

BACKGROUND OF THE INVENTION

In earlier patent applications, the inventor described the therapeutic use of non-β-oxidizing fatty acid analogues of the present invention for the treatment and prevention of obesity (NO 2000 5461), diabetes (NO 2000 5462), primary and secondary stenosis (NO 2000 5463), malignant tumors (NO 2002 5930), proliferative skin disorders (NO 2003 1080), inflammatory and autoimmune disorders (NO 2003 2054). In other earlier patent applications, the inventor described the therapeutic use of the protein materials of the present invention, including the protein material of unicellular organisms (NO 2003 3082) and the hydrolyzate of fish proteins (NO 2003 3078).

Unexpectedly, the authors of the present invention showed that the use of a combination of non-β-oxidizing structural elements of fatty acids with protein material provides synergistic beneficial biological effects. The inventors have shown that the combination of non-β-oxidizing structural elements of fatty acids with protein material leads to a decrease in plasma concentrations of cholesterol, triglycerides and phospholipids and to an increase in the activity of fatty acyl-CoA oxidase. In addition, the inventors describe how non-β-oxidizing structural elements of fatty acids and protein material can be directly added to animal feed. The food is easily digestible and has been shown to have unexpected effects on the composition of fatty acids in animals. Based on these unexpected discoveries, it is expected that a combination of non-β-oxidizing structural elements of fatty acids and protein material will have an increased prophylactic and / or therapeutic effect on all diseases against which non-β-oxidizing structural elements of fatty acids are effective, compared with the effect of structural elements of fatty acids separately.

SUMMARY OF THE INVENTION

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

1) fermented and / or hydrolyzed protein material,

2) one or more compounds containing non-β-oxidizing fatty acid structural element represented by

(a) the general formula R ″ is COO- (CH ₂ ) _{2n + 1} -X-R ′, where X is a sulfur atom, selenium atom, oxygen atom, CH ₂ group, SO group or SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, an atom selenium, an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group; 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 CH ₂ , and / or

(b) general formula (I),

where R1, R2 and R3 are

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 said R contains from 1 to 25 carbon atoms; or

iii) a group of the formula CO— (CH ₂ ) _{2n + 1} —X — R ′, wherein X represents a sulfur atom, a selenium atom, an oxygen atom, a CH ₂ group, an SO group or an SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, an atom selenium, an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group;

iv) a structural element selected from the group consisting of - PO ₃ CH ₂ CHNH ₃ COOH (phosphatidylserine), PO ₃ CH ₂ CH ₂ NH ₃ (phosphatidylethanolamine), PO ₃ CH ₂ CH ₂ N (CH ₂ ) ₃ (phosphatidylcholine), PO ₃ CH ₂ CHOHCH ₂ OH (phosphatidylglycerol) and PO ₃ (CHOH) ₆ (phosphatidylinositol); where R1, R2, and R3 are independently selected 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 CH ₂ and / or

(c) general formula (II),

where A1, A2 and A3 are independently selected and represent an oxygen atom, a sulfur atom or an N-R4 group, 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 are

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 is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of said R contains from 1 to 25 carbon atoms; or

iii) a group of the formula CO- (CH ₂ ) _{2n + 1} -X-R ', where X represents a sulfur atom, a selenium atom, an oxygen atom, a CH ₂ group, an SO group or an SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, an atom selenium, an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group;

iv) a structural element selected from the group consisting of - PO ₃ CH ₂ CHNH ₃ COOH (phosphatidylserine), PO ₃ CH ₂ CH ₂ NH ₃ (phosphatidylethanolamine), PO ₃ CH ₂ CH ₂ N (CH ₂ ) ₃ (phosphatidylcholine), PO ₃ CH ₂ CHOHCH ₂ OH (phosphatidylglycerol) and PO ₃ (CHOH) ₆ (phosphatidylinositol);

where R1, R2, and R3 are independently selected 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 CH ₂ , and / or

salts, prodrugs or complex of compounds according to claims (a) to (c) for the preparation of pharmaceutical or food compositions for the prevention and / or treatment of insulin resistance, obesity, diabetes, fatty liver infiltration, hypercholesterolemia, dyslipidemia, atherosclerosis, coronary heart disease, thrombosis, stenosis, secondary stenosis, myocardial infarction, stroke, high blood pressure, endothelial dysfunction, high blood coagulation, polycystic ovary syndrome, metabolic syndrome, malignant uholi, an inflammatory disorder, and proliferative skin disorders.

Preferably, said prophylaxis and / or treatment of a malignant tumor includes inhibition of: primary and secondary neoplasms, tumor growth, invasion of the primary tumor into the connective tissue, and formation of secondary tumors; the inflammatory disorder is selected from the group consisting of immune-mediated disorders, such as rheumatoid arthritis, systemic vasculitis, systemic lupus erythematosus, systemic scleroderma, dermatomyositis, polymyositis, various autoimmune endocrine disorders (e.g., thyroiditis and adrenalitis), various immune-mediated neurological disorders multiple sclerosis and myasthenia gravis), various cardiovascular disorders (e.g., myocarditis, congestive heart failure, arteriosclerosis and stable stable angina pectoris and Wegener's granulomatosis), inflammatory bowel disease and Crohn's disease, nonspecific colitis, pancreatitis, nephritis, cholestasis / liver fibrosis, acute and chronic transplant rejection after organ transplantation and diseases that have an inflammatory component, such as, for example, Alzheimer's disease or impaired / capable of improving cognitive function.

The indicated proliferative skin disorder is selected from the group consisting of psoriasis, atopic dermatitis, nonspecific dermatitis, primary irritant contact dermatitis, allergic contact dermatitis, lamellar ichthyosis, epidermolytic hyperkeratosis, precancerous sun-induced keratosis and seborrhea.

The invention further relates to the use of animal feed containing conventional feed components and a combination of:

1) fermented and / or hydrolyzed protein material,

2) one or more compounds containing non-β-oxidizing fatty acid structural elements represented by

(a) the general formula R ″ is COO- (CH ₂ ) _{2n + 1} -X-R ′, where X is a sulfur atom, selenium atom, oxygen atom, CH ₂ group, SO group or SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, an atom selenium, an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group; 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 CH ₂ and / or

(b) general formula (I),

where R1, R2 and R3 are

i) a hydrogen atom; or

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

iii) a group of the formula CO- (CH ₂ ) _{2n + 1} —X — R ′, wherein X represents a sulfur atom, a selenium atom, an oxygen atom, a CH ₂ group, an SO group or an SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, an atom selenium, an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group;

iv) a structural element selected from the group consisting of - PO ₃ CH ₂ CHNH ₃ COOH (phosphatidylserine), PO ₃ CH ₂ CH ₂ NH ₃ (phosphatidylethanolamine), PO ₃ CH ₂ CH ₂ N (CH ₂ ) ₃ (phosphatidylcholine), PO ₃ CH ₂ CHOHCH ₂ OH (phosphatidylglycerol) and PO ₃ (CHOH) ₆ (phosphatidylinositol);

where R1, R2, and R3 are independently selected 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 CH ₂ and / or

(c) general formula (II),

where A1, A2 and A3 are independently selected and represent an oxygen atom, a sulfur atom or an N-R4 group, 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 are

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 said R contains from 1 to 25 carbon atoms; or

iii) a group of the formula CO- (CH ₂ ) _{2n + 1} —X — R ′, wherein X represents a sulfur atom, a selenium atom, an oxygen atom, a CH ₂ group, an SO group or an SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, an atom selenium, an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group;

iv) a structural element selected from the group consisting of - PO ₃ CH ₂ CHNH ₃ COOH (phosphatidylserine), PO ₃ CH ₂ CH ₂ NH ₃ (phosphatidylethanolamine), PO ₃ CH ₂ CH ₂ N (CH ₃ ) ₃ (phosphatidylcholine), PO ₃ CH ₂ CHOHCH ₂ OH (phosphatidylglycerol) and PO ₃ (CHOH) ₆ (phosphatidylinositol);

where R1, R2, and R3 are independently selected 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 CH ₂ and / or

salts, prodrugs or complex compounds according to paragraphs. (a) - (c) to improve the overall composition of lipids in the animal.

Preferably, improving the overall lipid composition includes lowering the total level of lipids in the body, more preferably, decreasing the total level of saturated fatty acids in the body or increasing the total level of n-3 fatty acids in the body.

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

Further, the compound containing the non-β-oxidizing fatty acid structural element is a non-(3-oxidizing fatty acid, in particular tetradecylthioacetic acid (TTA), tetradecylselenoacetic acid and / or 3-thia-15-heptadecin; and X represents a sulfur atom or a selenium atom.

A compound containing a non-β-oxidizing fatty acid structural element may be a phospholipid, wherein said phospholipid is selected from the group consisting of phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol and / or diphosphatidylglycerol.

More specifically, a compound containing a non-β-oxidizing fatty acid moiety may be a 1,2-ditetradedecylthioacetoyl-sn-glycero-3-phosphocholine phosphatidylcholine derivative, a 1,2-ditetradedecylthioacetoyl-sn-glycerolol-3-phosphatidylethanolamine derivative, mono-, di- or triacylglyceride, in particular triacylglyceride containing tetradecylthioacetic acid (TTA).

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

Preferably, said composition is administered or given with food to an animal or human. The animal may be 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 specified animal may be a fish or shellfish, such as salmon, cod, tilapia, bivalves, oysters, lobster or crabs.

The daily dose of compounds containing non-β-oxidizing structural elements of 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.

The daily dose of protein material is approximately 5-500 mg / kg, preferably 50-300 mg / kg, for human consumption, and from 5 mg / kg up to the total daily protein intake for animal consumption.

The 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 the total daily cost of fat for animal consumption.

The animal feed of the invention may be a food composition, a veterinary composition, and / or a functional food product.

The invention further relates to a composition for preventing and / or treating insulin resistance, obesity, diabetes, fatty liver, hypercholesterolemia, dyslipidemia, atherosclerosis, coronary heart disease, thrombosis, stenosis, secondary stenosis, myocardial infarction, stroke, high blood pressure, endothelial dysfunction, conditions of increased blood coagulation, polycystic ovary syndrome, metabolic syndrome, malignant tumor, inflammatory disorders and proliferative skin disorders where the specified composition contains a combination of:

1) fermented and / or hydrolyzed protein material,

2) one or more compounds containing non-β-oxidizing fatty acid structural elements represented by

(a) the general formula R ″ is COO- (CH ₂ ) _{2n + 1} -X-R ′, where X is a sulfur atom, selenium atom, oxygen atom, CH ₂ group, SO group or SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, an atom selenium, an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group; 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 CH ₂ and / or

(b) general formula (I),

where R1, R2 and R3 are

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 said R contains from 1 to 25 carbon atoms; or

iii) a group of the formula CO- (CH ₂ ) _{2n + 1} -X-R ', where X represents a sulfur atom, a selenium atom, an oxygen atom, a CH ₂ group, an SO group or an SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group;

iv) a structural element selected from the group consisting of - PO ₃ CH ₂ CHNH ₃ COOH (phosphatidylserine), PO ₃ CH ₂ CH ₂ NH ₃ (phosphatidylethanolamine), PO ₃ CH ₂ CH ₂ N (CH ₂ ) ₃ (phosphatidylcholine), PO ₃ CH ₂ CHOHCH ₂ OH (phosphatidylglycerol) and PO ₃ (CHOH) ₆ (phosphatidylinositol);

where R1, R2, and R3 are independently selected 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 CH ₂ and / or

(c) general formula (II),

where A1, A2 and A3 are independently selected and represent an oxygen atom, a sulfur atom or an N-R4 group, 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 are

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 is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of said R contains from 1 to 25 carbon atoms; or

iii) a group of the formula CO- (CH ₂ ) _{2n + 1} -X-R ', where X represents a sulfur atom, a selenium atom, an oxygen atom, a CH ₂ group, an SO group or an SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, an atom selenium, an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group;

iv) a structural element selected from the group consisting of - PO ₃ CH ₂ CHNH ₃ COOH (phosphatidylserine), PO ₃ CH ₂ CH ₂ NH ₃ (phosphatidylethanolamine), PO ₃ CH ₂ CH ₂ N (CH ₃ ) ₃ (phosphatidylcholine), PO ₃ CH ₂ CHOHCH ₂ OH (phosphatidylglycerol) and PO ₃ (CHOH) ₆ (phosphatidylinositol);

where R1, R2, and R3 are independently selected 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 CH ₂ and / or

salts, prodrugs or complex compounds according to paragraphs. (a) - (C).

Preferably, the aforementioned protein material is selected from the group comprising protein material of unicellular organisms (SCP), a protein hydrolyzate of fish, and fermented soy protein material (e.g., Gendaxin®).

Also preferably, the composition according to the invention contains a daily dose of a compound containing a non-β-oxidizing fatty acid analog, 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 animal consumption.

In addition, the composition may further comprise vegetable and / or fish oil; a compound comprising a non-β-oxidizing fatty acid structural element is a β-oxidizing non-fatty acid, in particular tetradecylthioacetic acid (TTA), tetradecylselenoacetic acid and / or 3-thia-15-heptadecin; and X represents a sulfur atom or a selenium atom.

In addition, a compound containing a non-β-oxidizing fatty acid structural element may be a phospholipid selected from the group consisting of phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol, and / or diphosphatidylglycerol; or a derivative of 1/2-ditetradecylthioacetoyl-sn-glycero-3-phosphocholine phosphatidylcholine; or a derivative of phosphatidylethanolamine 1,2-ditetradecylthioacetoyl-sn-glycero-3-phosphoethanolamine.

Alternatively, a compound containing a non-β-oxidizing fatty acid structural element is a mono-, di- or triacylglyceride containing tetradecylthioacetic acid (TTA).

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

Preferably, the composition contains a daily dose of protein material of about 5-500 mg / kg, preferably 50-300 mg / kg, for human consumption and from 5 mg / kg up to the total daily protein intake for animal consumption.

In addition, the composition according to the invention may contain a daily dose of oil of approximately 1-300 mg / kg, preferably 10-150 mg / kg, for human consumption and from 1 mg / kg up to the total daily cost of fat for animal consumption.

In this case, the composition may be an animal feed, additionally containing conventional food components, for example fish food, in particular, salmon food, and conventional food components contain fish meal and / or fish oil.

The invention also relates to a method for producing a product of animal origin with an improved composition of fatty acids, comprising feeding an animal intended to produce a product with an animal feed containing conventional feed components and a combination of:

1) fermented and / or hydrolyzed protein material,

2) one or more compounds containing non-β-oxidizing structural elements of fatty acids displayed

(a) the general formula R ″ is COO- (CH ₂ ) _{2n + 1} -X-R ′, where X is a sulfur atom, selenium atom, oxygen atom, CH ₂ group, SO group or SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, an atom selenium, an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group; 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 CH ₂ and / or

(b) general formula (I),

where R1, R2 and R3 are

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 said R contains from 1 to 25 carbon atoms; or

iii) a group of the formula CO— (CH ₂ ) _{2n + 1} —X — R ′, wherein X represents a sulfur atom, a selenium atom, an oxygen atom, a CH ₂ group, an SO group or an SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group;

iv) a structural element selected from the group consisting of - PO ₃ CH ₂ CHNH ₃ COOH (phosphatidylserine), PO ₃ CH ₂ CH ₂ NH ₃ (phosphatidylethanolamine), PO ₃ CH ₂ CH ₂ N (CH ₃ ) ₃ (phosphatidylcholine), PO ₃ CH ₂ CHOHCH ₂ OH (phosphatidylglycerol) and PO ₃ (CHOH) ₆ (phosphatidylinositol);

where R1, R2, and R3 are independently selected 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 CH ₂ and / or

(c) general formula (II),

where A1, A2 and A3 are independently selected and represent an oxygen atom, a sulfur atom or an N-R4 group, 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 are

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 is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of said R contains from 1 to 25 carbon atoms; or

iii) a group of the formula CO— (CH ₂ ) _{2n + 1} —X — R ′, wherein X represents a sulfur atom, a selenium atom, an oxygen atom, a CH ₂ group, an SO group or an SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, an atom selenium, an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group;

iv) a structural element selected from the group consisting of - PO ₃ CH ₂ CHNH ₃ COOH (phosphatidylserine), PO ₃ CH ₂ CH ₂ NH ₃ (phosphatidylethanolamine), PO ₃ CH ₂ CH ₂ N (CH ₃ ) ₃ (phosphatidylcholine), PO ₃ CH ₂ CHOHCH ₂ OH (phosphatidylglycerol) and PO ₃ (CHOH) ₆ (phosphatidylinositol);

where R1, R2, and R3 are independently selected 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 CH ₂ and / or

salts, prodrugs or complex compounds according to paragraphs. (a.) - (C).

The above product of animal origin may be a meat product, an oil-based product or a skin-based product.

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

1) protein material and

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

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

Said prophylaxis and / or treatment of a malignant tumor preferably includes inhibition of:

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

In accordance with the invention, the inflammatory disorder is selected from the group consisting of immune-mediated disorders, such as rheumatoid arthritis, systemic vasculitis, systemic lupus erythematosus, systemic scleroderma, dermatomyositis, polymyositis, various autoimmune endocrine disorders (e.g., thyroiditis and adrenalitis), various immunologically mediated disorders (e.g., multiple sclerosis and myasthenia gravis), various cardiovascular disorders (e.g., myocarditis, congestive heart failure, arterio sclerosis and stable and unstable angina and Wegener's granulomatosis), inflammatory bowel diseases and Crohn's disease, nonspecific colitis, pancreatitis, nephritis, cholestasis / liver fibrosis, acute and chronic transplant rejection after organ transplantation and diseases that have an inflammatory component, such as, for example , Alzheimer's disease or impaired / capable of improving cognitive function.

Moreover, this proliferative skin disorder can be selected from the group consisting of psoriasis, atopic dermatitis, nonspecific dermatitis, primarily irritant contact dermatitis, allergic contact dermatitis, lamellar ichthyosis, epidermolytic hyperkeratosis, pre-malignant keratosis and seborrhea induced by the action of the sun.

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

The daily dose of protein material can be approximately 5-500 mg / kg, preferably 50-300 mg / kg, for human consumption, and from 5 mg / kg up to the total daily protein intake for animal consumption.

The 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 the total daily cost of fat for animal consumption.

In this case, the animal feed of the invention may be a food composition, a veterinary composition, and / or a functional food product.

The invention further relates to a composition for the prevention and / or treatment of hypercholesterolemia and conditions that are negatively affected by elevated cholesterol, insulin resistance, obesity, diabetes, fatty liver, dyslipidemia, atherosclerosis, coronary heart disease, thrombosis, stenosis, secondary stenosis, myocardial infarction, stroke, high blood pressure, endothelial dysfunction, high blood coagulation, polycystic ovary syndrome, metabolic syndrome, malignant tumor, inflammatory disorders and proliferative skin disorders, comprising a combination of:

1) protein material and

2) vegetable oil or fish oil,

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

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

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

Also, the composition may contain a daily dose of oil of approximately 1-300 mg / kg, preferably 10-150 mg / kg, for human consumption and from 1 mg / kg up to the total daily cost of fat for animal consumption.

Preferably, the composition may be an animal feed, further comprising conventional food components.

More preferably, the animal feed is fish food, in particular salmon, and conventional food components comprise fish meal and / or fish oil.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to the use of a preparation containing a combination of:

1) protein material,

2) one or more compounds containing non-β-oxidizing fatty acid structural elements represented by

(a) the general formula R ″ is COO- (CH ₂ ) _{2n + 1} -X-R ′, where X is a sulfur atom, selenium atom, oxygen atom, CH ₂ group, SO group or SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, an atom selenium, an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group; and R ″ represents a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms; and / or

(b) general formula (I),

where R1, R2 and R3 are

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 said R contains from 1 to 25 carbon atoms; or

iii) a group of the formula CO- (CH ₂ ) _{2n + 1} -X-R ', where X represents a sulfur atom, a selenium atom, an oxygen atom, a CH ₂ group, an SO group or an SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, an atom selenium, an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group;

iv) a structural element selected from the group consisting of —PO ₃ CH ₂ CHNH ₃ COOH (serine), PO ₃ CH ₂ CH ₂ NH ₃ (ethanolamine), PO ₃ CH ₂ CH ₂ N (CH ₃ ) ₃ (choline), PO ₃ CH ₂ CHOHCH ₂ OH (glycerol) and PO ₃ (CHOH) ₆ (inositol); where R1, R2, and R3 are independently selected from i), ii), iii) or iv), but at least one of R1, R2, or R3 is defined as iii); and / or

(c) general formula (II),

where A1, A2 and A3 are independently selected and represent an oxygen atom, a sulfur atom or an N-R4 group, 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 are

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 is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of said R contains from 1 to 25 carbon atoms; or

iii) a group of the formula CO- (CH ₂ ) _{2n + 1} -X-R ', where X represents a sulfur atom, a selenium atom, an oxygen atom, a CH ₂ group, an SO group or an SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, an atom selenium, an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group;

iv) a structural element selected from the group consisting of —PO ₃ CH ₂ CHNH ₃ COOH (serine), PO ₃ CH ₂ CH ₂ NH ₃ (ethanolamine), PO ₃ CH ₂ CH ₂ N (CH ₃ ) ₃ (choline), PO ₃ CH ₂ CHOHCH ₂ OH (glycerol) and PO ₃ (CHOH) ₆ (inositol);

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

salts, prodrugs or complex compounds according to claims. (a) - (c).

In a preferred embodiment, the compounds of this invention at least one of R1, R2, or R3 is alkyl.

In a preferred embodiment, the compounds of this invention at least one of R1, R2, or R3 is alkene.

In a preferred embodiment, the compounds of this invention at least one of R1, R2 or R3 is alkine.

In a preferred embodiment of the compound of this invention, at least one of R1, R2, or R3 is tetradecylthioacetic acid.

In a preferred embodiment, the compounds of this invention at least one of R1, R2 or R3 is tetradecylselenoacetic acid.

Preferred embodiments of the compounds of this invention are non-β-oxidizing fatty acids.

In a preferred embodiment of the compound of this invention, X represents a sulfur atom or a selenium atom.

Preferred embodiments of the compounds of this invention are tetradecylthioacetic acid (TTA), tetradecylselenoacetic acid and 3-thia-15-heptadecin.

In a preferred embodiment of the compound of this invention, n is 0 or 1.

In a preferred embodiment of the compound of this invention, said compound is a phospholipid, wherein said phospholipid is selected from the group consisting of phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol, diphosphatidylglycerol.

In a preferred embodiment of the compound of this invention, said compound is triacylglycerol.

In a preferred embodiment of the compound of this invention, said compound is diacylglycerol.

In a preferred embodiment of the compound of this invention, said compound is monoacylglycerol.

In a preferred embodiment of the compound of this invention, said compound is a derivative of phosphatidylcholine (PC) 1,2-ditetradecylthioacetoyl-sn-glycero-3-phosphocholine.

In a preferred embodiment of the compound of this invention, said compound is a derivative of phosphatidylethanolamine (PE) 1,2-ditetradecylthioacetoyl-sn-glycero-3-phosphoethanolamine.

Preferred embodiments of the compounds of this invention are mono-, di- or triacylglycerides.

Preferred embodiments of the compounds of this invention are triacylglycerides containing tetradecylthioacetic acid (TTA).

In a preferred embodiment of the compound of formula (II), each of A1 and A3 represents an oxygen atom, while A2 represents a sulfur atom or an N-R4 group 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 are essentially recognized by the same systems that process natural compounds, including enzymes that effect β-oxidation and, in some cases, ω-oxidation of natural long chain fatty acids. Analogs differ from their natural equivalents in that they cannot be completely oxidized in this way.

The compounds of this invention may be non-β-oxidizing fatty acid analogues, as represented by the formula R ″ CCO- (CH ₂ ) _{2n + 1} —X-R ′. However, these compounds can also be more complex structures derived from one or more of these non-β-oxidizing fatty acid analogues, as represented by general formulas (I) or (II). These compounds are analogues of natural mono-, di- and triacylglycerols or phospholipids, including phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol and diphosphatidylglycerol. These compounds may also contain a glycerol substitution in the backbone as described in formula (II). Said substitution of oxygen (s) is achieved by replacing oxygen (s) with a group containing sulfur or nitrogen. This can block hydrolysis before capture in the small intestine, thereby increasing the bioavailability of the compounds.

The above complex structures obtained from one or more of these non-β-oxidizing fatty acid structural elements exert their effect because they contain fatty acid analogues that are not capable of complete β-oxidation. These complex structures can have an effect as whole structures and as products formed due to the natural degradation of products containing fatty acid analogues. Due to the fact that the compounds are not capable of complete β-oxidation, they accumulate and this triggers an increase in the β-oxidation of natural fatty acids. Many of the effects of the compounds of this invention are a consequence of such an increase in β-oxidation.

During β-oxidation, the enzymatically oxidized fatty acid splits between carbon atoms 2 and 3 (if counted from the carboxyl end of the fatty acid), which leads to the removal of two carbon atoms on each side of the oxidation site in the form of acetic acid. This step is then repeated with the fatty acid just shortened by two carbon atoms and is repeated again until the fatty acid is completely oxidized. β-oxidation is the usual way in which most fatty acids are catabolized in vivo. Blocking β-oxidation by the compounds of this invention is achieved by embedding the non-oxidizing group at position X of the formula of the present invention. Due to the well-known mechanism of β-oxidation, X is defined as S, O, SO, SO ₂ , CH ₂ or Se. One of skill in the art can admit, without inventive step, that these compounds will all block β-oxidation in a similar manner.

In addition, the connections may contain more than one block, i.e. in addition to X, R ′ may optionally contain one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group. As an example, in order to cause changes in the degradation of a fatty acid and thus obtain a modulated effect, two or three sulfur atoms can be inserted as X. A large number of sulfur atoms to some extent also leads to a change in polarity and stability. From a pharmacological point of view, in order to avoid or prevent problems associated with resistance, it is generally more desirable to be able to obtain a set of compounds than just one compound.

In addition to structure X, its position is also a subject of discussion. The distance from X to the carboxyl end of the fatty acid is determined by the number of CH ₂ groups between X and the carboxyl end of the fatty acid, which is defined as (CH ₂ ) _{2n + 1} , where n is a number from 0 to 11. Thus, it turns out an odd number of CH ₂ groups, that is, the position of X relative to the carboxyl group is such that X ultimately blocks β-oxidation. The range of values of n is chosen so as to include all variants of the analogue of fatty acids, which has the desired biological effect. Since, theoretically, β-oxidation can act on molecules of unlimited length, n can be an infinite value, but in practice this is not so. The length of fatty acids, which normally undergo β-oxidation, is usually from 14 to 24 carbon atoms, and this length is thus most optimal for enzymatic β-oxidation. Thus, the ranges n and R ′ are given so that the structural elements of the fatty acids cover this range. (Similarly, in order to obtain analogues of natural compounds, parameter ii) of formulas (I) and (II) defines R as having from 1 to 25 carbon groups, and parameter i) of formula (II) defines an 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 for capturing the structural elements of the fatty acids of the present invention and their transport through cell membranes.

Despite the fact that analogues of fatty acids with an odd position of the β-oxidation blocker X, remote from the carboxyl end, block oxidation, the magnitude of their biological effect may vary. This is due to the difference in biological degradation time for different compounds. The inventors conducted experiments to show the effect of further removal of X from the carboxyl end of the fatty acid. In these experiments, the activity (nmol / min / mg / protein) of mitochondrial β-oxidation of fatty acid analogues in the liver was measured in the presence of sulfur at 3, 5, and 7 positions relative to the carboxyl end. The activity was 0.81 for sulfur in the 3 position, 0.61 for sulfur in the 5 position, 0.58 for sulfur in the 7 position and 0.47 for palmitic acid, which does not block the β-oxidation of the control. As expected, this shows that β-oxidation is indeed blocked by fatty acid analogues with different block positions, and that their effect decreases when the block position is further removed from the carboxyl end, because it takes longer to reach the block during β-oxidation, so that by then a greater amount of fatty acids is being degraded. However, since the deviation is significant when moving from 3 to 5 position, but small when moving from 5 to 7 position, it can reasonably be assumed that when moving along the chain this deviation will further decrease, and thus, by the time no effect will be observed at all (in comparison with the control), the position will certainly be significantly removed.

Thus, it is justified to include as compounds of the present invention the structural elements of fatty acids and other compounds represented by the general formulas (I) and (II) (which contain the indicated analogue (s) of a fatty acid) that block β-oxidation on various distances from the carboxyl end of analogues, such as compounds of the present invention, really blocking β-oxidation, even if the effect can be modulated. This modulation may ultimately vary under debilitating conditions; in various tissues, at depleting dosages, and when changing the analogue of fatty acids, so that it does not readily decompose, as described below. Thus, it is reasonable to include in the formula all the distances of the β-oxidation blocker from the carboxyl end of the fatty acid analogue, which are biologically suitable.

Despite the fact that the structural elements of fatty acids, as described, with a block in position X cannot be β-oxidized, they can nevertheless undergo ω-oxidation. This is a much less universal and slower biological process, in which the fatty acids are not oxidized from the carboxyl end, but rather from the methyl / hydrophobic end group, here denoted by R '. In this cascade, the carbon atom from the ω-terminus of the fatty acid is hydroxylated by a member of the cytochrome P450 enzyme family. Then this hydroxylated fatty acid is converted by an alcohol dehydrogenase to an aldehyde, and then this aldehyde is converted by an aldehyde dehydrogenase to a carboxyl group. As a result, the end product of the cascade is dicarboxylic fatty acid, which can be further degraded by ω-oxidation from the ω-end.

It is believed that ω-oxidation is the main pathway for the degradation of building blocks of fatty acids, as described, with a block at position X. Thus, experiments were performed where R 'was altered to block ω-oxidation by introducing a triple bond at the methyl end of the fatty acid analogue. The result was an analogue of the fatty acid 3-thia-15-heptadecin, for which the following expected results were shown during testing: a significantly increased in vivo degradation time. This is important for the use of the structural elements of fatty acids in a pharmaceutical preparation, since it can enhance the effects of β-oxidized structural elements of fatty acids by further reducing their breakdown.

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

In order to block ω-oxidation by embedding a substituent in R ′, said R ′ may be substituted in one or more positions by a hetero group selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom, an oxygen atom, a CH ₂ group, SO and a SO group ₂ . R 'may also be substituted with one or more compounds selected from the group consisting of fluoride, chloride, hydroxy, C ₁ -C ₄ alkoxy, C ₁ -C ₄ alkylthio, C ₂ -C ₅ acyloxy or C ₁ -C ₄ alkyl.

Thus, the compounds in accordance with the present invention are either fatty acids similar to natural fatty acids that are not capable of undergoing β-oxidation, or natural lipids containing these fatty acid analogues. It was shown that in vivo structural elements of fatty acids are strictly preferably incorporated into phospholipids. In some cases, it is indeed preferable to mimic the properties and incorporate the structural elements of fatty acids into natural lipids such as mono-, di- and triglycerides and phospholipids. This leads to a change in the absorption of the compounds (when comparing fatty acids with fatty acids embedded in larger lipid structures) and may increase bioavailability or stability.

For example, you can get the complex by embedding a fatty acid (s), which is not able to undergo β-oxidation, in triacylglycerol. Such compounds are encompassed by formulas (I) and (II). When orally administered with such triacylglycerol, for example, in an animal feed product, it is likely to be transported like any triacylglycerol from the small intestine in chylomicrons and from the liver in blood lipoproteins for storage in adipose tissue or for use in muscle, heart or liver, with hydrolysis triacylglycerol to glycerol and 3 free fatty acids. Free fatty acids at this stage will be the starting compound of the present invention, and will no longer be a complex.

Other possible glycerophospholipid fatty acid derivatives of the present invention include, but are not limited to, phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositols, phosphatidylserines and phosphatidylglycerols.

Another method of esterification of fatty acids, identified in vivo, which can be easily used to obtain a complex with the compound of the present invention, can be to obtain an alcohol or polyalcohol corresponding to a fatty acid, for example, you can obtain a sphingolipid derivative, such as ceramide or sphingomyelin, to obtain the corresponding amino alcohol . Like glycerophospholipid complexes, such complexes can be highly insoluble in water and less hydrophilic. These types of hydrophobic complexes of the present invention will more easily pass through biological membranes.

Other possible polar complexes of the present invention may include, but are not limited to, lysophospholipids, phosphatidic acid, alkoxy compounds, glycerocarbons, gangliosides and cerebrosides.

Although there may be large structural differences between different compounds containing non-β-oxidizing structural elements of the fatty acids of the present invention, it can be expected that the biological functions of all such compounds are very similar due to the fact that they all block β-oxidation in a similar way. Such inability of the structural elements of fatty acids to β-oxidation (and in some cases, to ω-oxidation) leads to the accumulation of analogues in mitochondria, which trigger β-oxidation in vivo of natural fatty acids, which in turn leads to many biological effects of the 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).

The cascade of β-oxidation of fatty acids is the main pathway for fat metabolism. The initial and speed-limiting reaction is carried out by acyl-CoA oxidase in liver peroxisomes. Acyl-CoA oxidase catalyzes the dehydrogenation of acyl-CoA-thioesters to the corresponding trans-2-enoyl-CoA. The fatty acid analogue of formula (I), tetradecylthioacetic acid (TTA), the inventors have previously used to analyze various biological effects of fatty acids. For the present invention, its effect on acyl-CoA oxidase, as well as the effect of the protein material, were analyzed separately or in combination.

The particular protein material analyzed here is a fermented soy protein material. Also in the process of analysis, the authors of the present invention is the protein material of unicellular organisms and a hydrolyzate of fish proteins. Despite the fact that these materials are complex and contain not only protein, the authors of the present invention believe that the protein part acts as the active ingredient, enhancing the therapeutic effects of non-β-oxidizing fatty acids of the present invention. Based on the results for the fermented soy protein material described herein, the present inventors expect similar results for the protein material of unicellular organisms and a fish protein hydrolyzate.

When analyzing for the presence of acyl CoA oxidase activity for TTA alone, a significant increase in activity was shown compared to the negative control. The fermented protein material of soybean alone practically did not have activity. But with the combined use of TTA and fermented soy protein material, the activity of acyl-CoA oxidase was more than twice as high as that of TTA alone. Such an increase in TTA as an activator of acyl-CoA oxidase by the fermented soy protein material was completely unexpected. The enhancement could definitely not be explained by the additive effect of TTA and the fermented soy protein material; unexpected synergistic effect was much stronger.

For the present invention, the effect of non-β-oxidizing structural elements of fatty acids on plasma phospholipids was also analyzed, as well as the effect of fermented soy protein material, alone or in combination with TTA. TTA led to a decrease in the level of phospholipids as compared with the control, while the fermented soy protein material essentially increased the level of phospholipids. However, with the combined use of TTA and fermented soy protein material, the level of phospholipids unexpectedly decreased to a greater extent than the level for TTA alone. Such an increase in the fermented protein material of soybean TTA as a means of lowering plasma phospholipids was completely unexpected. As in the case of acyl CoA oxidase activity, the enhancement also cannot be explained by the additive effect of TTA and the fermented soy protein material.

For the present invention, the effect of non-β-oxidizing structural elements of fatty acids, as well as the effect of fermented soy protein material, alone or in combination with TTA, on plasma cholesterol were also analyzed. The effects of fish oil were also analyzed separately, with TTA, with fermented soy protein material, or with both TTA and fermented soy protein material. It has been shown that TTA alone leads to a significant reduction in plasma cholesterol, and fermented soy protein material or fish oil alone also have the effect of lowering cholesterol. For the fermented protein material of soy and fish oil, a decrease in cholesterol levels to a greater extent was also shown than for each of them individually. When fish oil or fermented soy protein material was added to TTA, the effect of lowering cholesterol was unexpectedly higher than the effect of TTA alone. With the simultaneous addition of all three components: TTA, fish oil and fermented soy protein material, the effect on lowering cholesterol levels was greatest. This synergy effect between TTA, fish oil and fermented soy protein material was completely unexpected.

TTA has been shown to lower plasma triglycerides due to increased mitochondria and stimulated mitochondrial β-oxidation of common saturated and unsaturated fatty acids to ketone bodies (Froyland L et al. (1997) J Lipid Res 38: 1851-1858). For the present invention, it was found that this effect is further unexpectedly enhanced by the addition of fermented soy protein material. In these experiments, the results for the fermented soy protein were completely surprising and unexpected. TTA, as expected, lowers triglycerides. Fermented soy protein alone essentially increases triglyceride levels by 30% compared with the control, but nevertheless enhances the effect of TTA in relation to a 50% reduction in triglycerides. These synergistic effects were also very unexpected.

For the present invention, the effect of feeding Atlantic salmon with a feed containing non-β-oxidizing fatty acid analogues, common feed components, and fermented soy protein material was analyzed. In Example 2.1, the fish food consisted of coated conventional fish oil feed pellets, including TTA and fermented soy protein material. Such food was then used in Example 2.2 as a feed for Atlantic salmon, and the presence of TTA had beneficial effects on the fish food thus obtained compared to an equivalent food without TTA (Examples 2.3 and 2.4).

Commonly used feed pellets mainly contain fish feed meal, some wheat, and vitamin and mineral supplements. The oil used to coat the granules was also of marine origin, from capelin, and contained various amounts of TTA mixed with it. Table 1 describes the composition and chemical composition of the diets. The food was a regular food, well suited for the species being analyzed (in this example, Atlantic salmon), for which beneficial effects were shown with the addition of TTA.

As previously shown in this application, TTA, introduced together with the protein has an additional beneficial effect compared to the effect of TTA separately. The fact that this regular food is a high-fat and low-carbohydrate food probably enhances the beneficial effects of TTA compared to the effects of TTA, administered alone or in conjunction with a high-carb diet.

In Example 2.4, the effects of a particular protein material, a fermented soy protein material, were determined. Fermented soy protein material is obtained by fermenting soy beans. It contains modified and unmodified soy proteins and isoflavones, as well as other components of soy. In a preferred embodiment of the invention, Gendaxin® fermented soy protein material is used.

Table 2 describes the composition of the fatty acids of the diets. There were very slight differences in the composition of dietary fatty acids (all contained approximately 100% fish oil), the percentage of n-3 fatty acids (FA) was almost the same. The diet to which TTA was added, at the same time, led to significant changes in the percentage of n-3 fatty acids phospholipids (PL), triacylglycerols (TAG) and free fatty acids (FFA) in the gills, heart and liver of Atlantic salmon. The introduction of TTA for 8 weeks also led to a decrease in the percentage of saturated FA in almost all lipid fractions. The percentage of n-3 FA, especially DHA, increased in the gills and heart, as can be seen in example 2.3.

Atlantic salmon fed a diet containing TTA grew slower than fish fed a control diet. The lipid level in the body of fish fed a diet supplemented with TTA was significantly lower than the level of fish fed a control diet.

There are beneficial effects on the health of the fish themselves, which were fed the food of this invention. In old fish, arterial sclerosis can develop and lead to health problems, as in humans, and a decrease in lipids has a beneficial effect in this regard.

In general, it is believed that lean meats obtained by the method of the present invention are useful in most animal species that are bred for consumption. Thus, the effect of lowering the overall level of lipids in itself is advantageous. In addition, specific changes in the composition of fatty acids are particularly positive. It is generally recognized that consuming less saturated fatty acids is good for health, and increased n-3 intake is associated with health benefits for the whole body, from reducing the likelihood of heart disease to anti-inflammatory effects and even to increase intelligence in children.

Other animal products derived from animals fed with the food of the present invention may also have beneficial effects. As an example, the fish oil obtained in this way will have a superior nutritional composition compared to fish oil, which was fed a commercial diet. Other foods, such as fish skins, may also have the beneficial effects observed when improving the tissue composition of the whole organism.

The level of fatty acids in the blood is normally determined by the relative rates of fat breakdown and esterification in adipose tissue and muscle fatty acid intake. In muscles, fatty acids inhibit glucose uptake and oxidation. Elevated levels of fatty acids and triacylglycerol in the blood and muscles, therefore, correlate with obesity and insulin resistance, as well as with a decrease in the 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 showed the presence of stimulation of the oxidation of fatty acids and a decrease in the concentration of fatty acids in plasma of non-β-oxidizing structural elements of fatty acids and protein material, also optionally containing an oil component. The authors of the present invention, therefore, expect that the compositions of the present invention can be used for the prevention and treatment of insulin resistance and related diseases (Shulman GI (2000) J Clin Invest 106 (2): 171-176). TTA has been found to completely prevent high-fat diet-induced insulin resistance and obesity, and to reduce obesity, hyperglycemia, and insulin sensitivity in obese rats (Madsen M et al. (2002) J Lipid Res 43 (5): 742 -fifty). Due to the unexpected synergistic results found by the inventors using both TTA and protein material, and optionally oil, without confirmation by any particular theory explaining the results, the present inventors now expect that such a combination will be even more effective in treating these conditions. The authors of the present invention also expect that the effect of TTA will be enhanced by protein material, and optionally by oil, in the treatment of similar diseases and disorders, including high blood pressure, high lipids and cholesterol, endothelial dysfunction, high blood coagulation, polycystic ovary syndrome and metabolic syndrome.

The Peroxisome Proliferator Activated Receptor (PPAR) family is a pleiotropic regulator of cellular functions such as cell proliferation, differentiation, and lipid homeostasis (Ye JM et al. (2001) Diabetes 50: 411-417). The PPAR family contains 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 an activator, PPARα TTA stimulates the catabolism of fatty acids by increasing their cellular consumption. A decrease in plasma triglycerides by TTA causes a switch in the liver cell metabolism towards regulated PPARα fatty acid catabolism in mitochondria. (Graf HJ et al. (2003) J Biol Chem 278 (33): 30525-33). Although the effect of TTA on plasma triacylglycerols is determined by the activation of PPARα, as shown by the elimination of this effect in PPARα knockout mice, fish oil does not cause a decrease in plasma triacylglycerol even in knockout mice (Dallongeville J et al. (2001) J Biol Chem 276: 4634-4639).

Supplementing the diet with n-3 polyunsaturated fatty acids, similar to those found in fish oil, stimulates the activity of acyl CoA oxidase in liver peroxisomes 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). A diet with an increased fish oil content has been shown to increase both the activity and the mRNA level of fatty acid oxidation enzymes by peroxisomes and liver mitochondria (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 peroxide acyl-CoA oxidase in the liver, but not in the muscles of rats, and the authors suggested that this is due to the fact that n-3 fatty acids protect against insulin resistance induced by fats, acting as PPARα ligands inducing proliferation of peroxisomes in the liver (not intramuscular). The expression of the PPARα gene did not change. (Neschen S et al. (2002) Am J Physiol Endocrinol Metab 282: E395-E401)

As can be seen in the above paragraphs, the biochemical details of how TTA, protein material and optionally oil affect fat metabolism are not known in detail. Effects may or may not be mediated in one way, both TTA and oils may, for example, act as PPARα ligands or independently of PPARα. If they act in the same way, then TTA enhancement with oils cannot be expected, due to the fact that TTA is a strong PPARα activator, which can be expected to fully ensure PPARα activation. Even when added, the effect of TTA and oil when combined will be unexpected. Even less is known about how protein affects β-oxidation or other aspects of fat metabolism. Thus, the effects of simultaneous administration of protein material and TTA cannot be predicted. However, obtaining a synergistic effect above the additive effect, as can be seen for TTA and fermented soy protein material in all trials of the present invention, was very unexpected. The β-oxidizable structural elements of fatty acids have many effects, and the authors of the present invention do not know how they all arise, but based on the unexpected results of the present invention, the authors expect that they will all be enhanced by protein material and optionally oils, without confirmation of which or a specific theory.

PPAR ligands disrupt the proliferation of various cancer cell lines. 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 Pharmacol 61: 639-649; Tronstad KJ et al. (2001) Lipids 36: 305-313). This decrease is associated with a decrease in the level of triacylglycerols (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). Since fermented soy protein increases the ability of TTA to lower triacylglycerols, it is therefore very likely that it will also increase the antiproliferative effects of TTA, providing such an increase in the ability of TTA to prevent and treat malignant tumors. TTA can be used for the prevention and / or treatment of a malignant tumor, including the inhibition of: primary and secondary neoplasms, tumor growth, invasion of the primary tumor into the connective tissue and the formation of secondary tumors (NO 2002 5930).

Typically, PPAR agonists modulate the inflammatory response. TTA modulates the inflammatory response by suppressing the release of the inflammatory cytokine interleukin-2 and suppressing PHA-stimulated proliferation of peripheral mononuclear cells (Aukrust P et al. (2003) Eur J Clin Invest 33 (5): 426-33). Modulation of the cytokine by TTA can be mediated by PPAR or by altering the level of prostaglandins, or by modifying lipid-mediated signal transduction, the latter of which is also a possible mechanism of action of polyunsaturated fatty acids, such as those found in oils. Now that the inventors have found unexpected results with respect to the present invention, they are thus expecting the protein material and optionally oil, in combination with non-β-oxidizing fatty acid structural elements, to enhance the effect of fatty acid structural elements on inflammatory disorders, including immune-mediated disorders such as rheumatoid arthritis, systemic vasculitis, systemic lupus erythematosus, systemic scleroderma, dermatomyositis, polymyositis, various autoimmuses endocrine disorders (e.g., thyroiditis and adrenalitis), various immune-mediated neurological disorders (e.g., multiple sclerosis and myasthenia gravis), various cardiovascular disorders (e.g., myocarditis, congestive heart failure, arteriosclerosis and stable and unstable angina pectoris, and Wegener's granulomatosis), inflammatory diseases bowel disease, Crohn’s disease, nonspecific colitis, pancreatitis, nephritis, cholestasis / liver fibrosis, acute and chronic transplant rejection after organ transplantation, also proliferative skin disorders such as psoriasis, atopic dermatitis, nonspecific dermatitis, primarily irritant contact dermatitis, allergic contact dermatitis, lamellar ichthyosis, epidermolytic hyperkeratosis, precancerous sun-induced karatosis and seborrhea, and diseases that have an inflammatory component Alzheimer's or impaired / capable of improving cognitive function.

DESCRIPTION OF DRAWINGS

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

Figure 2 shows that the effect of TTA in reducing phospholipids is enhanced by fermented soy protein material.

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

Figure 4 shows that the effects of TTA in reducing triacylglycerols are enhanced by the fermented soy protein material.

DEFINITIONS USED IN THE APPLICATION

Animals

In this context, the term "animals" includes mammals, such as humans and farm (farm) animals, especially animals of economic importance, such as chicken, mammals related to cattle, sheep, goats and pigs, especially animals, through which get products suitable for human consumption, such as meat, eggs and milk. It is further understood that the term includes fish and shellfish such as salmon, cod, tilapia, bivalves, oysters, lobster or crabs. The term also includes domestic animals, such as dogs and cats.

Pet food

The term "animal feed" refers to food for animals (as defined above). Animal food, as a rule, contains the appropriate amounts of fats, proteins, carbohydrates, vitamins and minerals necessary for the life support of a particular recipient animal, and may contain additional components to improve the taste, texture, color, smell, stability, shelf life, etc. e., or antibiotics or other components added for the benefit of the animal’s health. Animal feed is preferably, but not necessarily, a dry substance, most preferably a granular substance. The term “animal feed” is also intended to include food compositions, veterinary compositions, and / or functional foods for animal consumption.

Meat

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

Vegetable Fats and / or Fish Oil

They include all types of oils of vegetable or marine origin, including, but not limited to, fatty or non-volatile oils, as well as essential or volatile oils, and any combination thereof. They do not have to be in liquid form. The sunflower oil that was used for the present invention is in fact an oil from sunflower seeds, and not from the flower itself.

Fish fat

This term includes all types of oil of marine origin.

Food composition

It is understood that this term includes any ingestible substance, including, but not limited to, nutritional supplements, functional foods, herbal supplements, etc. for human and animal consumption. The term also includes foods for human consumption and animal feed, where the composition of the present invention is an additional component, and not the main ingredient. This is especially true for animal feed, where any food can be supplemented with the composition of the present invention to achieve its biological effects.

Treatment

With respect to pharmaceutical aspects of the use of this invention, the term “treatment” refers to a reduction in the severity of a disease.

Prevention

The term "prophylaxis" refers to the prevention of a given disease, i.e. the compound of the present invention is administered before the development of the condition. This means that the compounds of the present invention can be used as prophylactic agents or as ingredients in a food composition in order to prevent the risk or development of this disease.

Fermentation

The breakdown of organic substances by microorganisms or enzymes, including hydrolysis.

Hydrolysis

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

Protein Material from Unicellular Organisms (SCP)

SCP is a material found in unicellular microorganisms. In particular, microorganisms can be fungi, yeast and bacteria. SCP material has a high relative protein content.

Enzyme Treated Fish Protein Hydrolyzate (FPH)

FPH material is a protein hydrolyzate obtained by enzymatic treatment of fish material. FPH material has a high relative content of proteins and peptides.

Fermented Soy Protein Material

Fermented soy protein material is obtained by fermenting soy beans. It contains modified and unmodified soy proteins and isoflavones, as well as other components of soy.

Food composition

It is understood that this term includes material used internally, including, but not limited to, nutritional supplements, functional foods, herbal supplements, etc. for human or animal consumption. The term also includes foods for human consumption and animal feed, where the composition of the present invention is an additional component and is not a main ingredient. This is especially true for animal feed, where any food can be supplemented with the composition of the present invention to achieve its biological effects.

INTRODUCTION OF THE COMPOUNDS OF THE PRESENT INVENTION

As a pharmaceutical drug, the composition of the present invention can be administered directly to the animal by any suitable method, including parenteral, intranasal, oral administration, or by absorption through the skin. It can be administered locally or systemically. The particular route of administration of each agent depends, for example, on the history of the human or animal recipient.

Examples of parenteral administration include subcutaneous, intramuscular, intravenous, intraarterial and intraperitoneal administration.

As a general point, the total pharmaceutically effective amount of each of the non-β-oxidizable structural elements of fatty acids administered parenterally in a dose is preferably in the range of about 1 mg / kg / day to 200 mg / kg / day per patient body weight for humans although, as described above, it is possible to carry out a significant therapeutic separation. A dose of 5-50 mg / kg / day is most preferred. A dose of fermented soy protein material or other protein material of 5-500 mg / kg / day is preferred, and a dose of 50-300 mg / kg / day is most preferred. A dose of fish oil or other oil of 1-300 mg / kg / day is preferred, and a dose of 10-150 mg / kg / day of fish oil or other oil is most preferred.

When administered continuously, all compounds of the present invention are typically administered as 1-4 injections per day or by continuous subcutaneous infusions, for example, using a mini-dispenser. A solution from an intravenous bag may also be used. The main factor in choosing the appropriate dose is the final result, determined by reducing the total body weight or the ratio of fat to muscle mass, or by other criteria of the measured control, or by preventing obesity or preventing obesity-related conditions, as determined by an appropriately qualified specialist.

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

Typically, the compositions are obtained by combining the compounds of the present invention with liquid carriers, or finely divided solid carriers, or with both, in a uniform and uniform mixture. Then, if necessary, the product is shaped into the desired preparation. 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 solution. Non-aqueous vehicles, such as fatty oils and ethyl oleate, as well as liposomes, are also suitable here.

If appropriate, the carrier may contain small amounts of additional components, such as substances that increase isotonicity and chemical stability. Such substances are not toxic to the recipient in the dosages and concentrations used and include buffers such as phosphate, citrate, succinate, acetate buffer and other buffers based on 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 hydrocarbons, including cellulose or its derivatives, glucose, mannose or dextrins; chelating agents such as EDTA; sugar based alcohols such as mannitol or sorbitol; counterions such as sodium; and / or nonionic surfactants, such as polysorbates, poloxamers, or PEG.

In the case of oral pharmacological compositions, carriers such as water, gelatin, gums, lactose, starches, magnesium stearate, talc, oils, polyalkylene glycol, liquid paraffin, and the like can be used. Such a pharmaceutical preparation may be in unit dosage form and may additionally contain other therapeutically useful substances or conventional pharmaceutical adjuvants, such as preservatives, stabilizers, emulsifiers, buffers, and the like. The pharmaceutical preparations can be in the form of conventional liquid forms, such as tablets, capsules, dragees, ampoules, and the like, in the form of conventional dosage forms, such as ampoules, and in the form of suppositories and the like.

In addition, the compounds of the present invention, i.e. analogues of non-β-oxidizing fatty acids and protein material or analogues of non-β-oxidizing fatty acids and protein material and oil can be used in food preparations as defined above, in which the dosage of non-β-oxidizing fatty acid analogues is dosage, as for the described drugs or below, while the amount of protein material and oil is preferably suitable for the manufacture of food and feed materials. As part of the food composition, and especially animal feed, oil and protein material can be a significant part of the feed, and thus have nutritional value and also enhance the effects of non-β-oxidizing fatty acid analogues. Fish oil may include up to all fats of the nutritional composition, and fermented soy protein material may include up to all proteins of the food composition. In animal feed, the amount of non-β-oxidizing fatty acid analogue can be up to 10 times higher than in products for human consumption, i.e. up to 2 g / kg / day per animal body weight. Such animal feed can be used for daily feeding of animals. The fermented protein material of soybean is particularly suitable as a functional protein in food products, in particular when used as a substitute for natural plasma in animal feed and pet food. The animal feed composition may also contain additional ingredients such as fats, sugars, salt, flavors, minerals, etc. In addition, the product can be shaped into pieces similar to natural pieces of meat in appearance and consistency. The product according to this invention has additional advantages in that it is easy to manufacture with the necessary food additives, it is easily digested by animals and has an attractive taste for animals.

EXPERIMENTAL PART

The preparation of the non-β-oxidizing structural elements of the fatty acids of the present invention is described in detail in earlier Norwegian patent applications No. 20005461, 20005462, 20005463 and 20024114 of the applicant. These documents also describe TTA toxicity studies. The preparation of mono-, di- and triglycerides and nitrogen-containing lipids in accordance with this invention is described in detail in US patent application No. 10/484350. A phospholipid preparation comprising serine, ethanolamine, choline, glycerin and inositol according to this invention is described in detail in Norway's earlier patent application No. 20045562 of the applicant.

The experimental results below show that the protein material and / or oil substantially enhances the biological effects of non-β-oxidizing fatty acid analogues.

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

1.1 Obtaining a hydrolyzate of fish proteins (FPH)

Source materials

FPH was obtained from the remnants of muscle tissue of fish on the skeleton after cutting on a fillet. Headless skeletons of freshly salted Atlantic salmon fillet (Salmon Salar, L.) were obtained directly from the production line and frozen at -20 ± 2 ° C. Within a week, frozen skeletons were used for the enzymatic hydrolysis process.

Hydrolysis

Enzymatic hydrolysis was performed using Protamex ^™ at a pH of approximately 6.5 and at a temperature of 55 ± 2 ° C. Protamex ^™ (EC 3.4.21.62/3.4.24.28) is a Bacillus protease complex from Novozymes AS (Bagsverd, Denmark) and corresponds to the purity required for food enzymes. The ratio of salmon skeletons to water was 1.14. The enzyme to substrate ratio of 11.1 EA / kg of crude protein was used for hydrolysis. After 60 minutes of enzymatic treatment, the temperature was raised to 98 ° C, which was reached after 105 minutes.

Cleaning

Large bones were left in the tank for hydrolysis, and small bones were removed by filtering the hydrolyzate 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 three-phase separator (Westfalia, Germany, SB-7-36- + 76, 4 kW, 8520 rpm) for salmon oil, emulsion fraction and water fraction. The aqueous fraction was concentrated (NitroAtomicer, Denmark, a falling film evaporator, Ff 100), filtered through an ultrab Membrane with a passport molecular weight limit of 100,000 (PCI, UK, PF100 membrane systems, 2.65 m ² ) and finally the ultrafiltered fraction ( UF fraction) was spray dried (Niro Atomizer, Denmark, P-63 column, T _inside = 200 ° C, T _outside = 84 ° C).

Final product

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

1.2 Obtaining protein material of unicellular organisms (SCP)

Source materials

A microbial culture containing Methylococcus capsulatus (Bath), Ralstonia sp., Brevibacillus agri and Aneurinibacillus sp, all commercially available in Norferm Denmark AS, Odense, Denmark, was obtained in a loop fermenter by continuous fermentation of natural gas in an environment of ammonium salt / mineral salts (AMS) at 45 ° C, pH 6.5 and at a dilution rate of 0.15 h ^-1 . A liter of medium contained the following components: 10 mg NH ₃ , 75 mg H ₃ PO ₄ · 2H ₂ O, 380 mg MgSO ₄ · 7H ₂ O, 100 mg CaCl ₂ · 2H ₂ O, 200 mg K ₂ SO ₄ , 75 mg FeSO ₄ · 7H ₂ O, 1.0 mg CuSO ₄ · 5H ₂ O, 0.96 mg ZnSO ₄ · 7H ₂ O, 120 μg CoCl ₂ · 6H ₂ O, 48 μg MnCl ₂ · 4H ₂ O, 36 μg H ₃ BO ₃ , 24 μg NiCl ₂ · 6H ₂ O and 1.20 μg NaMoO ₄ · 2H ₂ O.

Getting

The fermenter was filled with water, which was sterilized by heating for 10 seconds at 125 ° C. Additional nutritional supplements were adjusted according to their intake. Continuous fermentation was carried out for 2-3% biomass (based on dry weight).

The material of unicellular organisms was obtained continuously and subjected to centrifugation in a continuous industrial centrifuge at 3000 rpm, followed by ultrafiltration using membranes with a maximum size of 100,000 Daltons. Then, the resulting product was sterilized in a heat exchanger for approximately 90 seconds at approximately 130 ° C.

Additional SSP features can be found in the previous applicant application No. 2003 3082. The synthesis of SSP is provided as an example, and not to illustrate the synthesis of all protein materials or even protein materials of unicellular organisms of formula (I).

1.3 Fermented Soy Protein Material

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

1.4 Biological effects of the compositions of this invention in rats

Chemical reagents

Chemical reagents were obtained from generally accepted commercial sources, and they were chemically pure. As a control (negative), carboxymethyl cellulose (CMC) was used. Fish oil was commercially available from Hordafor.

Animals

Male Wistar rats weighing from 250 to 358 g were purchased from AnLab Ltd. (Prague, Czech Republic) and kept in wire cages at a temperature of 22 ± 1 ° C and in a room with controlled lighting (light from 7 to noon to 7 in the afternoon). There were no restrictions on the intake of food and water. Three rats were kept in each cage. Weight gain and feed intake were determined every day.

Rations

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

Introduction

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

Killing and tissue removal

Rats were anesthetized with a 1: 1 mixture of 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), administered subcutaneously. Blood was drawn directly from the heart using a heparin-washed syringe. The liver was immediately removed, weighed and divided into two parts, which were immediately cooled on ice or frozen in liquid nitrogen, respectively. Plasma and tissues were stored at -80 ° C until analysis. The protocol was approved by the Norwegian Office of Biological Experiments on Live Animals.

Obtaining subcellular hepatic fractions

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

Enzyme analysis

Fat acyl CoA oxidase activity was measured in the peroxisomal fraction of the liver as previously described (Small GM, Burdett K, Connock MJ (1985) Biochem J 227: 205-10). The results were presented as the activity of fatty acyl-CoA oxidase relative to the total protein, the initial activity (control activity) was subtracted, the data presented in FIG. 1, normalized with respect to TTA activity.

Lipid analysis

Plasma and liver lipids were enzymatically determined on a Technicon Axon system (Miles, Territown, NY) using a Bayer triglyceride kit, for total cholesterol (Bayer, Territown, NY) and a PAP 150 kit for phospholipids containing choline from bioMerieux. Results are presented relative to total protein. The results were presented relative to the total protein, and the data presented in FIG. 2-4, were normalized with respect to the activity of the positive control (without the addition of TTA or oils; ie, a “normal" level). The results were presented relative to the total protein, and the data presented in FIG. 2-4, were normalized with respect to the activity of the positive control (without the addition of TTA or oils; ie, a “normal" level).

Example 2

The biological effects of the composition of this invention in Atlantic salmon

2.1 Experimental model, including obtaining food for fish

An experimental fish meal diet was provided by EWOS and contained 0.01% Y ₂ O ₃ as an inert marker for determining digestibility (3 mm pellets). Table 1 presents the compositions and chemical compositions of the three types of diets. All three types of diets were obtained from a single feed mixture. Various diets were obtained by coating conventional feed pellets with various oils and mixtures. Diets included either fish oil (capelin oil) (control), fish oil supplemented with 0.5% TTA (0.5% TTA) or fish oil supplemented with 1.5% TTA (1.5% TTA).

The composition of fatty acids in diets clearly reflects that fish oil (capelin oil) was used (table 2). Capelin fat contained a relatively high level of monounsaturated FA and was also enriched with long chain n-3 FAs, 20: 5 n-3 (EPA) and 22: 6 n-3 (DHA). The food, however, contained a significant amount of fish meal, which contained n-3 FA, providing a higher level of these FAs in the diet than in the added oil.

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

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

2.2: Growing Atlantic salmon in feed containing TTA

Fish, conditions and experimental design

The test was conducted at AKVAFORSK Research Station, Sunndalsora, Norway. Atlantic salmon (Salmon salar) with an average initial mass of approximately 86 g was placed in 15 cylindrical conical containers (diameter 0.85 m), 40 each. The containers were filled with sea water at a constant temperature of 12 ° C. The fish were allowed to adjust to temperature and fed commercial food for two weeks before the start of the test. The growing test consisted of a time period of 8 weeks.

The diets were rations as described in Table 2 above, which either contained fish oil (capelin oil) (control), or fish oil supplemented with 0.5% TTA (0.5% TTA), or fish oil supplemented with 1, 5% TTA (1.5% TTA). Three rations were randomly assigned to three containers. The feed was distributed using an electric feed system (Akvaprodukter AS, Sunndalsora). The tanks were designed so that excess feed was collected from the waste water into wire frame boxes. Excess feed was collected, and this allowed us to calculate the mass of feed consumed.

A diet including Gendaxin was used in a separate experiment, but the experimental design was similar to that described above.

Initial and final sampling

Fish were not fed for 2 days before the initial sampling of images. Six fish from each tank were anesthetized with MS-222 at the beginning and end of the experiment, and the average weight and average length were determined. These six fish were killed by a blow to the head and the abdominal cavity was opened. Samples of the liver, heart, gills, and kidneys were immediately frozen in liquid nitrogen and stored at -80 ° C. These samples were then used to analyze the composition of fatty acids. An additional five fish from each tank were anesthetized and killed. These fish were used to determine the composition of the whole body.

Before the final sampling of the fish, the feeding of the fish did not stop. Excrement samples were isolated from five fish from each tank according to the method described by Austreng (Aquaculture, 1978 13: 265-272). Before analysis, excrement samples from each container were pooled. Samples were stored at -20 ° C.

The second branchial arch was removed from the fish, which was anesthetized, and washed with ice-cold SEI buffer (150 mM sucrose, 10 nM EDTA, 50 mM imidazole, pH 7.3) and immediately frozen in liquid nitrogen. Gill tissue was stored at -80 ° C. The liver was homogenized in icy sucrose.

Growth

The average weight of fish in groups with all diets approximately tripled during the test, from the initial value of 86 g to the final value of approximately 250 g. SGR decreased with increasing doses of TTA in the diet, from SGR 1.8 in the control group to SGR 1.7 in the group c 0.5% TTA and SGR 1.5 in the group with 1.5% TTA (table 3). There were no significant differences in fatness ratios between dietary groups (table 3).

Feed intake and digestibility

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

For the content of proteins, fats and energy and individual fatty acids in the diet of Atlantic salmon containing Control: fish oil, 0.5% TTA: fish oil with the addition of 0.5% TTA, 1.5% TTA: fish oil with the addition of 1, 5% TTA

Data are mean ± SEM

Values in the same row with different superscripts are significantly different; nd = not defined.

2.3 Biological effects of TTA

Chemical reagents

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). HCl methanol solution and 2,2-dimethoxypropane were purchased from Supelco Inc. (Bellfonte, PA, USA). K6 silica gel-coated tablets were obtained from Whatman International Ltd. (Maidstone, UK).

Chemical analysis

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

Lipid Extraction and Fatty Acid Analysis

Total lipids were extracted from homogenized gills, liver and heart using the method described by Folch (J Biol Chem 1957 226: 497-509). The phase of chloroform-methanol from the gills was dried in a 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 the mobile phase. Lipids were visualized by spraying on TLC plates 0.2% (w / v) 2'7'-dichlorofluorescein in methanol and were identified by comparison with known standards under UV light.

The spots corresponding to PL, FFA, and TAG were cleaned into glass tubes and then trans-methylated overnight with 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 a non-polar column with fused capillaries of gas chromatography as described by Rosjo (Fish Physiol Biochem 1994 13: 119-132). FA methyl esters were separated on a gas chromatograph (Perkin-Elmer Auto system GC, equipped with an injector, programmable injector with separation / without separation) with a CP wax 52 column (with a length of 25 m, an inner diameter of 0.25 mm and a film thickness of 0.2 μm ), a flame ionization detector, and a 1022 data system. The carrier gas was He, and the temperature of the injector and detector was 280 ° C. The temperature of the furnace was raised from 50 ° C to 180 ° C at a rate of 10 ° C min ^-1 and then raised to 240 ° C at a speed of 0.7 ° C min ^-1 . The relative amount of each fatty acid present was determined by measuring the peak area corresponding to that acid.

Calculations

The apparent digestibility coefficient (ADC) was calculated as described by Austreng (Aquaculture, 1978 13: 265-272). Fatness ratio (CF), hepatosomatic index (HSI), specific growth factor (SGR) and growth rate per heat unit (TGC) were calculated as follows, based on individual weight and length indicators:

SGR = (e ^{(ln W1-ln W0) / day)} -1) 100

TGC = (W ₁ ^1/3 -W ₀ ^1/3 ) 1000 / (day ° C)

where W ₀ represents the initial mass, W ₁ represents the final mass, t represents the temperature during the day.

CF = 100 · W · (Smith length) ^-3

HSI = 100 · liver mass · W ^-1

Statistical analysis

One-way analysis of variance (ANOVA) was performed for all data and the differences were ranked according to the Duncan multiple comparison criterion. Significance level was set at 5%.

Body and liver composition

Fish fed a diet with 1.5% TTA had lower body lipids (9.6%) than fish fed a control diet (10.6%) (Table 5). There were no statistically significant differences in the total lipid content between the fish fed the control diet and the fish fed the diet with TTA (table 6). The hepatosomatic index was significantly higher in fish fed a diet with 1.5% TTA (1.2%) than in fish fed a control diet (1.1%) (Table 6).

Control: fish oil, 0.5% TTA: fish oil with 0.5% TTA, 1.5% TTA: fish oil with 1.5% TTA.

^{ab The} differences between the mean values in this series are significant (p <0.05), as indicated by different superscript letters.

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

The composition of the fatty acids of the liver, gills and heart

The composition of the fatty acids PL, TAG and FFA in the gills, liver and heart are presented in tables 7, 8 and 9. TTA was part of the PL fraction in the gills (0.8%) and heart (0.7%) of Atlantic salmon fed diet with 1.5% TTA. TTA was also part of the TG and FFA fractions in the gills (table 7). Traces of TTA and its products obtained under the action of Δ ⁹ desaturase were part of the liver lipids, while no products of Δ ⁹ desaturase were isolated from heart lipids and gills.

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

2.4 Biological effects of a composition of this invention comprising a fermented soy protein material

Chemical reagents

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

Lipid analysis

Plasma lipids were enzymatically determined using the Technicon Axon system (Miles, Tarrytown, NY) using a Bayer triglyceride kit, a total cholesterol kit (Bayer, Territown, NY), and a PAP 150 kit for choline-containing phospholipids from bioMerieux. The results are presented in mmol / l in table 10.

From the above data it is clear that the addition of Gendaxin to fish feed has a positive effect on the fatty acid composition in salmon plasma. The level of cholesterol, triglycerides and phospholipids with the addition of 0.25% Gendaxin in fish food decreased compared with the control. Further addition of Gendaxin and TTA further improved plasma fatty acid composition.

Enzyme analysis

The activity of fatty acyl CoA oxidase was determined in the 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 fatty acyl CoA oxidase relative to the total protein in table 11.

Table 11
β-oxidation in the liver Beta oxidation The control
0.5% Gendaxin + 0.9% TTA 0.940
1,501

From the above data, it is obvious that the addition of Gendaxin and TTA to fish food has a positive effect on β-oxidation, since β-oxidation is 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% fat

20% protein

5% fiber

10% sucrose

3.5% AIN93G Mineral Mixture

1.0% Vitamin AIN-93

Else: Starch

The fat component is 30% pork fat, or 2.5-5% pork fat is replaced by fish oil, or 0.15 pork fat is replaced by TTA. Protein material is 20% milk protein (casein), or half is replaced with fish protein or "Bioprotein".

Claims (82)

1. The use of a drug containing a combination of:
1) fermented and / or hydrolyzed protein material, and
2) one or more compounds containing non-β-oxidizing fatty acid structural element represented by
(a) the general formula R ″ is COO- (CH ₂ ) _{2n + 1} -X-R ′, where X is a sulfur atom, selenium atom, oxygen atom, CH ₂ group, SO group or SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, an atom selenium, an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group; 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 CH ₂ , and / or
(b) general formula (I),

where R1, R2 and R3 are
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 said R contains from 1 to 25 carbon atoms; or
iii) a group of the formula CO- (CH ₂ ) _{2n + 1} —X — R ′, wherein X represents a sulfur atom, a selenium atom, an oxygen atom, a CH ₂ group, an SO group or an SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group;
iv) a structural element selected from the group consisting of —PO ₃ CH ₂ CHNH ₃ COOH (phosphatidylserine), PO ₃ CH ₂ CH ₂ NH ₃ (phosphatidylethanolamine), PO ₃ CH ₂ CH ₂ N (CH ₂ ) ₃ (phosphatidylcholine), PO ₃ CH ₂ CHOHCH ₂ OH (phosphatidylglycerol) and PO ₃ (CHOH) ₆ (phosphatidylinositol);
where R1, R2 and R3 are independently selected 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 CH ₂ and / or
(c) general formula (II),

where A1, A2 and A3 are independently selected and represent an oxygen atom, a sulfur atom or an N-R4 group, 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 are
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 is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of said R contains from 1 to 25 carbon atoms; or
iii) a group of the formula CO- (CH ₂ ) _{2n + 1} —X — R ′, wherein X represents a sulfur atom, a selenium atom, an oxygen atom, a CH ₂ group, an SO group or an SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, an atom selenium, an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group;
iv) a structural element selected from the group consisting of —PO ₃ CH ₂ CHNH ₃ COOH (phosphatidylserine), PO ₃ CH ₂ CH ₂ NH ₃ (phosphatidylethanolamine), PO ₃ CH ₂ CH ₂ N (CH ₂ ) ₃ (phosphatidylcholine), PO ₃ CH ₂ CHOHCH ₂ OH (phosphatidylglycerol) and PO ₃ (CHOH) ₆ (phosphatidylinositol);
where R1, R2 and R3 are independently selected 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 CH ₂ and / or
salts, prodrugs or complex of compounds according to claims (a) to (c) for the preparation of pharmaceutical or food compositions for the prevention and / or treatment of insulin resistance, obesity, diabetes, fatty liver infiltration, hypercholesterolemia, dyslipidemia, atherosclerosis, coronary heart disease, thrombosis, stenosis, secondary stenosis, myocardial infarction, stroke, high blood pressure, endothelial dysfunction, high blood coagulation, polycystic ovary syndrome, metabolic syndrome, malignant uholi, an inflammatory disorder, and proliferative skin disorders. 2. The use according to claim 1, where the specified prevention and / or treatment of a malignant tumor includes inhibition of:
primary and secondary neoplasms, tumor growth, invasion of the primary tumor into the connective tissue and the formation of secondary tumors. 3. The use according to claim 1, where the inflammatory disorder is selected from the group consisting of immune-mediated disorders, such as rheumatoid arthritis, systemic vasculitis, systemic lupus erythematosus, systemic scleroderma, dermatomyositis, polymyositis, various autoimmune endocrine disorders (eg, thyroiditis and adrenalitis), various immune-mediated neurological disorders (e.g., multiple sclerosis and myasthenia gravis), various cardiovascular disorders (e.g., myocarditis, congestive heart failure, arteriosclerosis and stable and unstable angina pectoris and Wegener's granulomatosis), inflammatory bowel diseases and Crohn's disease, nonspecific colitis, pancreatitis, nephritis, cholestasis / liver fibrosis, and acute and chronic transplant rejection after organ transplantation, and diseases that have an inflammatory component, such as, for example , Alzheimer's disease or impaired / capable of improving cognitive function. 4. The use according to claim 1, wherein said proliferative skin disorder is selected from the group consisting of psoriasis, atopic dermatitis, nonspecific dermatitis, primarily irritant contact dermatitis, allergic contact dermatitis, lamellar ichthyosis, epidermolytic hyperkeratosis, and pre-malignant keratosis and seborrhea induced by the action of the sun. 5. The use of animal feed containing conventional food components and a combination of:
1) fermented and / or hydrolyzed protein material, and
2) one or more compounds containing non-β-oxidizing fatty acid structural elements represented by
(a) the general formula R ″ is COO- (CH ₂ ) _{2n + 1} -X-R ′, where X is a sulfur atom, selenium atom, oxygen atom, CH ₂ group, SO group or SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, an atom selenium, an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group; 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 CH ₂ and / or
(b) general formula (I),

where R1, R2 and R3 are
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 said R contains from 1 to 25 carbon atoms; or
iii) a group of the formula CO- (CH ₂ ) _{2n + 1} —X — R ′, wherein X represents a sulfur atom, a selenium atom, an oxygen atom, a CH ₂ group, an SO group or an SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group;
iv) a structural element selected from the group consisting of —PO ₃ CH ₂ CHNH ₃ COOH (phosphatidylserine), PO ₃ CH ₂ CH ₂ NH ₃ (phosphatidylethanolamine), PO ₃ CH ₂ CH ₂ N (CH ₂ ) ₃ (phosphatidylcholine), PO ₃ CH ₂ CHOHCH ₂ OH (phosphatidylglycerol) and PO ₃ (CHOH) ₆ (phosphatidylinositol);
where R1, R2 and R3 are independently selected 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 CH ₂ and / or
(c) general formula (II),

where A1, A2 and A3 are independently selected and represent an oxygen atom, a sulfur atom or an N-R4 group, 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 are
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 said R contains from 1 to 25 carbon atoms; or
iii) a group of the formula CO- (CH ₂ ) _{2n + 1} —X — R ′, wherein X represents a sulfur atom, a selenium atom, an oxygen atom, a CH ₂ group, an SO group or an SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, an atom selenium, an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group;
iv) a structural element selected from the group consisting of —PO ₃ CH ₂ CHNH ₃ COOH (phosphatidylserine), PO ₃ CH ₂ CH ₂ NH ₃ (phosphatidylethanolamine), PO ₃ CH ₂ CH ₂ N (CH ₂ ) ₃ (phosphatidylcholine), PO ₃ CH ₂ CHOHCH ₂ OH (phosphatidylglycerol) and PO ₃ (CHOH) ₆ (phosphatidylinositol);
where R1, R2 and R3 are independently selected 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 CH ₂ and / or
salts, prodrugs or complex compounds according to paragraphs. (a) - (c) to improve the overall composition of lipids in the animal. 6. The use according to claim 5, where the improvement in the overall composition of lipids includes a decrease in the total level of lipids in the body. 7. The use according to claim 5, where improving the overall composition of lipids includes reducing the total level of saturated fatty acids in the body. 8. The use according to claim 5, where improving the overall composition of lipids includes increasing the overall level of p-3 fatty acids in the body. 9. The use according to claim 1, where the specified protein material is a protein material of unicellular organisms (SCP). 10. The use according to claim 1, where the specified protein material is a hydrolyzed protein of fish. 11. The use according to claim 1, where the specified protein material is a fermented protein material of soy. 12. The use of claim 11, wherein said soy protein material is Gendaxin®. 13. The use according to claim 1, where the compound (s) containing non-β-oxidizing structural element of a fatty acid is a non-β-oxidizing fatty acid. 14. The use according to claim 13, wherein the compound (s) containing a non-β-oxidizing fatty acid structural element is tetradecylthioacetic acid (TTA), tetradecylselenoacetic acid and / or 3-thia-15-heptadecin. 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 (s) containing a non-β-oxidizing fatty acid structural element is a phospholipid, wherein said phospholipid is selected from the group consisting of phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol and / or diphosphatinidyl . 17. The use according to claim 1, where the compound containing non-β-oxidizing structural element of a fatty acid is a derivative of phosphatidylcholine 1,2-ditetradecylthioacetoyl-sn-glycero-3-phosphocholine. 18. The use according to claim 1, where the compound containing non-β-oxidizing structural element of a fatty acid is a derivative of phosphatidylethanolamine 1,2-ditetradecylthioacetoyl-sn-glycero-3-phosphoethanolamine. 19. The use according to claim 1, where the compound (s) containing a non-β-oxidizing fatty acid structural element is a mono-, di- or triacylglyceride. 20. The use according to claim 19, where the compound (s) containing a non-β-oxidizing fatty acid structural element is a triacylglyceride containing tetradecylthioacetic acid (TTA). 21. The use according to claim 1, where the composition further comprises vegetable and / or fish oil. 22. The use of claim 21, wherein the vegetable or fish oil contains polyunsaturated fatty acids. 23. The use of claim 22, wherein 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 administered or given with food to an animal. 25. The application of paragraph 24, where the 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, bivalves, oysters, lobster or crabs. 29. The use according to claim 1, where the daily dose of compounds containing non-β-oxidizing structural elements of 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 approximately 5-500 mg / kg, preferably 50-300 mg / kg, for human consumption and from 5 mg / kg up to the total daily protein intake for animal consumption. 31. The application of item 21, where the 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 the total daily cost of fats for animal consumption. 32. The use according to claim 5, where the animal feed may be a food composition, a veterinary composition and / or a functional food product. 33. Composition for the prevention and / or treatment of insulin resistance, obesity, diabetes, fatty liver, hypercholesterolemia, dyslipidemia, atherosclerosis, coronary heart disease, thrombosis, stenosis, secondary stenosis, myocardial infarction, stroke, high blood pressure, endothelial dysfunction conditions of increased blood coagulation, polycystic ovary syndrome, metabolic syndrome, malignant tumor, inflammatory disorders and proliferative skin disorders, characterized in that seemed composition comprises the combination of:
1) fermented and / or hydrolyzed protein material, and
2) one or more compounds containing non-β-oxidizing fatty acid structural elements represented by
(a) the general formula R ″ is COO- (CH ₂ ) _{2n + 1} -X-R ′, where X is a sulfur atom, selenium atom, oxygen atom, CH ₂ group, SO group or SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, an atom selenium, an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group; 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 CH ₂ and / or
(b) general formula (I),

where R1, R2 and R3 are
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 said R contains from 1 to 25 carbon atoms; or
iii) a group of the formula CO- (CH ₂ ) _{2n + 1} —X — R ′, wherein X represents a sulfur atom, a selenium atom, an oxygen atom, a CH ₂ group, an SO group or an SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group;
iv) a structural element selected from the group consisting of —PO ₃ CH ₂ CHNH ₃ COOH (phosphatidylserine), PO ₃ CH ₂ CH ₂ NH ₃ (phosphatidylethanolamine), PO ₃ CH ₂ CH ₂ N (CH ₂ ) ₃ (phosphatidylcholine), PO ₃ CH ₂ CHOHCH ₂ OH (phosphatidylglycerol) and PO ₃ (CHOH) ₆ (phosphatidylinositol);
where R1, R2 and R3 are independently selected 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 CH ₂ and / or
(c) general formula (II),

where A1, A2 and A3 are independently selected and represent an oxygen atom, a sulfur atom or an N-R4 group, 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 are
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 is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of said R contains from 1 to 25 carbon atoms; or
iii) a group of the formula CO- (CH ₂ ) _{2n + 1} —X — R ′, wherein X represents a sulfur atom, a selenium atom, an oxygen atom, a CH ₂ group, an SO group or an SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, an atom selenium, an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group;
iv) a structural element selected from the group consisting of —PO ₃ CH ₂ CHNH ₃ COOH (phosphatidylserine), PO ₃ CH ₂ CH ₂ NH ₃ (phosphatidylethanolamine), PO ₃ CH ₂ CH ₂ N (CH ₂ ) ₃ (phosphatidylcholine), PO ₃ CH ₂ CHOHCH ₂ OH (phosphatidylglycerol) and PO ₃ (CHOH) ₆ (phosphatidylinositol);
where R1, R2 and R3 are independently selected 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 CH ₂ and / or
salts, prodrugs or complex compounds according to paragraphs. (a) - (C). 34. The composition according to p, in which the specified protein material is a protein material of unicellular organisms (SCP). 35. The composition according to p, in which the specified protein material is a hydrolyzate of fish proteins. 36. The composition according to p, in which the specified protein material is a fermented protein material of soy. 37. The composition according to clause 36, in which the specified protein material of soy is a Gendaxin®. 38. The composition of claim 33, wherein the composition contains a daily dose of a compound containing a non-β-oxidizing fatty acid analog, 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 vegetable and / or fish oil. 40. The composition according to p, where the compound (s) containing not subject to β-oxidation of the structural element of a fatty acid, is not subject to β-oxidation of a fatty acid. 41. The composition of claim 40, wherein the compound (s) containing a non-β-oxidizing fatty acid structural element is tetradecylthioacetic acid (TTA), tetradecylselenoacetic acid and / or 3-thia-15-heptadecin. 42. The composition according to p, where X represents a sulfur atom or a selenium atom. 43. The composition of claim 33, wherein the compound (s) containing a non-β-oxidizing fatty acid structural element is a phospholipid, wherein said phospholipid is selected from the group consisting of phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol, and / or diphosphatidylglycerol. 44. The composition according to p. 33, where the compound containing non-β-oxidizing structural element of a fatty acid, is a derivative of phosphatidylcholine 1,2-ditetradecylthioacetoyl-sn-glycero-3-phosphocholine. 45. The composition according to p. 33, where the compound containing non-β-oxidizing structural element of a fatty acid, is a derivative of phosphatidylethanolamine 1,2-ditetradecylthioacetoyl-sn-glycero-3-phosphoethanolamine. 46. The composition of claim 33, wherein the compound (s) containing a non-β-oxidizing fatty acid structural element is a mono-, di- or triacylglyceride. 47. The composition according to item 46, where the compound (s) containing not subject to β-oxidation of the structural element of a fatty acid is a triacylglyceride containing tetradecylthioacetic acid (TTA). 48. The composition according to p, where the vegetable or fish oil contains polyunsaturated fatty acids. 49. The composition of claim 48, wherein the vegetable oil is selected from the group consisting of sunflower oil, soybean oil, and olive oil. 50. The composition according to p. 33, where the composition contains a daily dose of protein material of approximately 5-500 mg / kg, preferably 50-300 mg / kg, for human consumption and from 5 mg / kg up to the total daily cost of protein for animal consumption. 51. The composition according to p. 33, where the composition contains a daily dose of oil of approximately 1-300 mg / kg, preferably 10-150 mg / kg, for human consumption and from 1 mg / kg up to the total daily cost of fats for animal consumption. 52. The composition according to p. 33, where the composition is animal feed, optionally containing conventional food components. 53. The composition according to p, where the animal feed is a fish feed. 54. The composition according to p, where the fish feed is a salmon feed. 55. The composition according to p, where the conventional components of the feed contain fishmeal and / or fish oil. 56. A method of obtaining a product of animal origin with an improved composition of fatty acids, comprising feeding the animal intended to obtain the product, animal feed containing conventional food components and a combination of:
1) fermented and / or hydrolyzed protein material, and
2) one or more compounds containing non-β-oxidizing structural elements of fatty acids displayed
(a) the general formula R ″ is COO- (CH ₂ ) _{2n + 1} -X-R ′, where X is a sulfur atom, selenium atom, oxygen atom, CH ₂ group, SO group or SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, an atom selenium, an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group; 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 CH ₂ and / or
(b) general formula (I),

where R1, R2 and R3 are
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 said R contains from 1 to 25 carbon atoms; or
iii) a group of the formula CO- (CH ₂ ) _{2n + 1} —X — R ′, wherein X represents a sulfur atom, a selenium atom, an oxygen atom, a CH ₂ group, an SO group or an SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, a selenium atom an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group;
iv) a structural element selected from the group consisting of —PO ₃ CH ₂ CHNH ₃ COOH (phosphatidylserine), PO ₃ CH ₂ CH ₂ NH ₃ (phosphatidylethanolamine), PO ₃ CH ₂ CH ₂ N (CH ₂ ) ₃ (phosphatidylcholine), PO ₃ CH ₂ CHOHCH ₂ OH (phosphatidylglycerol) and PO ₃ (CHOH) ₆ (phosphatidylinositol);
where R1, R2 and R3 are independently selected 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 CH ₂ and / or
(c) general formula (II),

where A1, A2 and A3 are independently selected and represent an oxygen atom, a sulfur atom or an N-R4 group, 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 are
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 is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of said R contains from 1 to 25 carbon atoms; or
iii) a group of the formula CO- (CH ₂ ) _{2n + 1} —X — R ′, wherein X represents a sulfur atom, a selenium atom, an oxygen atom, a CH ₂ group, an SO group or an SO ₂ group; 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 said R' contains from 13 to 23 carbon atoms and optionally one or more hetero groups selected from the group consisting of an oxygen atom, a sulfur atom, an atom selenium, an oxygen atom, a CH ₂ group, an SO group and an SO ₂ group;
iv) a structural element selected from the group consisting of —PO ₃ CH ₂ CHNH ₃ COOH (phosphatidylserine), PO ₃ CH ₂ CH ₂ NH ₃ (phosphatidylethanolamine), PO ₃ CH ₂ CH ₂ N (CH ₂ ) ₃ (phosphatidylcholine), PO ₃ CH ₂ CHOHCH ₂ OH (phosphatidylglycerol) and PO ₃ (CHOH) ₆ (phosphatidylinositol); where R1, R2 and R3 are independently selected 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 CH ₂ , and / or
salts, prodrugs or complex compounds according to paragraphs. (a) - (C). 57. The method of claim 56, wherein the animal product is a meat product. 58. The method of claim 56, wherein the animal product is an oil based product. 59. The method of claim 56, wherein the animal product is a skin based product. 60. The use of a drug containing a combination of:
1) protein material and
2) vegetable oil or fish oil, in which the protein material is selected from the group comprising the protein material of unicellular organisms (SCP), a protein hydrolyzate of fish, a fermented protein material of soy, preferably Gendaxin®, to obtain a pharmaceutical or food composition for the prevention and / or treatment hypercholesterolemia and conditions that are negatively affected by elevated cholesterol, insulin resistance, obesity, diabetes, fatty liver, dyslipidemia, atherosclerosis, coronary heart disease thrombosis, stenosis, secondary stenosis, myocardial infarction, stroke, high blood pressure, endothelial dysfunction, high blood coagulation, polycystic ovary syndrome, metabolic syndrome, malignant tumor, inflammatory disorders and proliferative skin disorders. 61. The application of claim 60, wherein the vegetable oil or fish oil contains polyunsaturated fatty acids. 62. The use of claim 61, wherein the vegetable oil is selected from the group consisting of sunflower oil, soybean oil, and olive oil. 63. The application of claim 60, wherein said prophylaxis and / or treatment of a malignant tumor includes inhibition of:
primary and secondary neoplasms, tumor growth, invasion of the primary tumor into the connective tissue and the formation of secondary tumors. 64. The application of claim 60, wherein the inflammatory disorder is selected from the group consisting of immune-mediated disorders such as rheumatoid arthritis, systemic vasculitis, systemic lupus erythematosus, systemic scleroderma, dermatomyositis, polymyositis, various autoimmune endocrine disorders (eg, thyroiditis and adrenalitis), various immune-mediated 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 transplant rejection after organ transplantation, and diseases that have an inflammatory component, such as, for example, Alzheimer's disease or impaired / capable of improving cognitive function. 65. The application of claim 60, wherein said proliferative skin disorder is selected from the group consisting of psoriasis, atopic dermatitis, nonspecific dermatitis, primarily irritant contact dermatitis, allergic contact dermatitis, lamellar ichthyosis, epidermolytic hyperkeratosis, pre-malignant keratosis-induced keratosis and the sun. 66. The use according to any one of claims 60 to 65, wherein said composition is administered or given with food to an animal. 67. The application of claim 66, wherein said animal is a human. 68. The application of claim 66, wherein said animal is an agricultural animal such as chicken, mammals, cattle, sheep, goats or pigs. 69. The application of claim 66, wherein said animal is a pet or a pet, such as a dog or cat. 70. The application of claim 66, wherein said animal is a fish or shellfish, such as salmon, cod, tilapia, bivalves, oysters, lobster or crabs. 71. The application of claim 60, wherein 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 the total daily protein cost for animal consumption. 72. The application of claim 60, wherein the daily dose of oil is about 1-300 mg / kg, preferably 10-150 mg / kg, for human consumption and from 1 mg / kg up to the total daily cost of fat for animal consumption. 73. The application of claim 66, wherein the animal feed may be a food composition, a veterinary composition, and / or a functional food product. 74. Composition for the prevention and / or treatment of hypercholesterolemia and conditions that are negatively affected by elevated cholesterol, insulin resistance, obesity, diabetes, fatty liver infiltration, dyslipidemia, atherosclerosis, coronary heart disease, thrombosis, stenosis, secondary stenosis, myocardial infarction stroke, high blood pressure, endothelial dysfunction, high blood coagulation, polycystic ovary syndrome, metabolic syndrome, malignant tumor, inflammatory usheny and proliferative skin disorders, containing a combination of:
1) protein material and
2) vegetable oil or fish oil, in which the protein material is selected from the group comprising the protein material of unicellular organisms (SCP), a protein hydrolyzate of fish, a fermented soy protein material, preferably Gendaxin®. 75. The composition of claim 74, wherein the vegetable oil or fish oil contains polyunsaturated fatty acids. 76. The composition of claim 74, wherein the vegetable oil is selected from the group consisting of sunflower oil, soybean oil, and olive oil. 77. The composition according to p. 74, where the composition contains a daily dose of protein material of approximately 5-500 mg / kg, preferably 50-300 mg / kg, for human consumption and from 5 mg / kg up to the total daily cost of protein for animal consumption. 78. The composition according to p. 74, where the composition contains a daily dose of oil of approximately 1-300 mg / kg, preferably 10-150 mg / kg, for human consumption and from 1 mg / kg up to the total daily cost of fats for animal consumption. 79. The composition of claim 74, wherein the composition is animal feed, further comprising conventional feed components. 80. The composition of claim 74, wherein the animal feed is a fish feed. 81. The composition of claim 74, wherein the fish food is salmon food. 82. The composition of claim 74, wherein conventional feed components comprise fishmeal and / or fish oil.

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