Application of nutritive compositions for diseases prevention

FIELD: food industry.

SUBSTANCE: present invention relates to prevention of subsequent diseases by way of a specific nutritive composition prescription to children at an age of up to 3 years. One proposes the composition application; for production of the nutritive composition for: prevention and/or therapy of visceral adiposopathy and/or prevention and/or therapy of visceral fat mass accumulation up to an excessive quantity where the nutritive composition is prescribed for administration to a child at an age of 0 - 36 months. The composition contains a lipid, a protein components and a digestible carbohydrates component. The lipid component accounts for 35 - 55% of the total calorie content and contains less than 14.5 wt % of linoleic acid of the total fatty acids weight, the weight ratio of linoleic acid (LA) to alfa-linolenic acid (ALA) is 2 - 6. The protein component accounts for 5 - 15% of the total calorie content, the digestive carbohydrates component for 30-60% of the total calorie content. Additionally the composition may contain galactooligosaccharides, long chain polyunsaturated fatty acids (LC-PUFA) and 10-50 wt % of medium-chain fatty acids (MCFA).

EFFECT: invention allows to prevent development of disorders related to visceral adiposopathy with humans at an age over 36 months.

18 cl, 5 tbl, 4 ex

 

The technical FIELD TO WHICH the INVENTION RELATES

The present invention relates to the prevention of later disease by assigning specific nutrient composition children under the age of 3 years. The present invention relates in a special way to prevent visceral adiposity.

The LEVEL of TECHNOLOGY

Breastfeeding is the preferred method of feeding infants. It is assumed that breastfeeding in the early stages of life may influence the occurrence of diseases in later life.

However, there are conditions under which breastfeeding is not possible or desirable. In such cases, a good alternative are milk formulas for infants and nutrient mixture for the older children.

The modern compositions of mixtures for feeding babies or infant formula for children of older age are selected in such a way that they meet the many special requirements of the rapidly growing and developing baby.

It is obvious that the composition of milk powder for baby food can still be improved. For example, little is known about the influence of the ingredients of baby food on health in later life. The present invention relates to effects on Zdor the Vieux in the future.

WO 2005063050 describes a method of increasing lean body mass and reduce body fat mass of children by receiving timely or early, nutrient mixture containing a source of DHA (docosahexaenoic acid) and ARA (arachidonic acid). WO 2006057551 relates to child nutrition, containing at least one protease inhibitor, the method of making such baby food and child nutrition for the treatment and/or prevention of childhood obesity and secondary disorders associated with childhood obesity. WO 03005836 describes dietary products for infants, children and adults nutrition, which involves appropriate levels of content and the ratio of medium chain fatty acids and omega-polyunsaturated fatty acids. The use of such diet products can contribute to the prevention of obesity in developing individual and reduction of body fat mass of individuals who are trying to lose weight or reduce body weight (for example, overweight people). WO 2006069918 describes the way the continuous reduction of the level of circulating insulin-like growth factor 1 (IGF-1) in the first few months of a child's life by assigning to receive nutritional compositions containing proteins in such amounts that the composition contains less than 2.25 g of protein per 100 kcal. Because IGF-1 is known as to uchiwa control point in the nutritional regulation of growth, may be a method of reducing the risk of developing obesity later in life. In the work Aillaud and coauthors, 2006, Progress in Lipid research 45:203-236, discusses the role of n6 polyunsaturated fatty acids in excessive adipose tissue development and relationship to obesity.

The INVENTION

The authors of the present invention has revealed certain gaps in current knowledge about the relationship between nutrition in early childhood and the development of diseases later in life.

The authors of the present invention found that the total fat mass of children is not a good indicator for determining the risk of disease in later life. Body fat can be distributed and stored in adipose tissue in various body sites. Different fat tissues have different metabolic effects, especially in children. Subcutaneous fat in children has an important function in maintaining appropriate body temperature. Fat located in the Central part of the body (visceral fat), serves only as a "store" energy. Moreover, located in different places of the fat cells differ in size and profile of secretion of proteins that are potential regulators of glucose homeostasis and fat. It is important that the mass of visceral fat is metabolically highly active tissue, which releases free fatty acids is directly into the hepatic portal vein. The resulting flow of free fatty acids contribute to the metabolism of glucose and the sensitivity of the liver to insulin and, therefore, can lead to metabolic disorders. Therefore, the greatest contribution to the development of certain disorders in later life, most likely contributes to the development of mass visceral fat in early childhood (visceral adiposity in early childhood). The mass accumulation of visceral fat, as it turns out, makes the greatest contribution to the development of disorders, especially disorders of metabolism and the cardiovascular system, regardless of obesity. Moreover, people may suffer from General obesity, but not from visceral adiposity, whereas others may suffer from visceral adiposity, but not from General obesity (Lemieux et al, 1996, Am J Clin Nutr, 64:685-693; Carey, 1998, Curr Opinio Lipidology 9:35-40, Matsuzawa et al, 1995, Obesity Research 3 suppl 2: 187-194). Thus, visceral adiposity differs from the total of obesity not only in relation to the risk of secondary disorders in later life, but also in patient populations.

Therefore, the results of this discovery the purpose of the present invention is the prevention of disorders in older age and lower education adipocytes visceral fat in childhood.

It was found that in early childhood and, to a lesser extent, within pubertatis the period is determined by the number of visceral adipocytes. At other stages of life mass visceral fat "only" increased by filling adipocyte fat. The number of cells remains approximately the same throughout adult life. Therefore, it is highly desirable to reduce the proliferation of visceral adipocytes in early childhood without excessive weight reducing subcutaneous fat. Reduction in visceral adipocytes prevents disease at a later age.

Establish appropriate measures to modify the proliferation of visceral adipocytes in children is particularly difficult because the purpose of pharmaceutical drugs in General is undesirable and the power can not be rigidly changed, because the child needs to receive sufficient nutrients for normal growth and development. In addition, the target reduction in fat mass may be disadvantageous, for example, for the reason that the mass of subcutaneous fat plays an important role in maintaining body temperature. Therefore, the main aim of the present invention is to reduce the accumulation of visceral fat mass in children and/or reduce the accumulation of visceral adipocytes fat, preferably at a later age, through the development appointed by the diet of the child, which guarantees the maintenance of normal growth and development.

The authors of this izobreteny is found nutrient composition, which reduces visceral obesity and other disorders in later life, in particular diabetes (especially type 2 diabetes), hyperglycemia, fasting, insulin resistance, hyperinsulinemia, hypertension, cardiovascular disease, cerebrovascular disease, arthrosclerosis, dyslipidemia, hyperuricemia, fatty infiltration of the liver, osteoarthritis and sleep apnea (stop breathing) during sleep.

The inventors have experimentally confirmed that the appointment to receive at an early age diet, in which the lipid component is relatively poor in terms of linoleic acid (LA) and has a low ratio of linoleic acid/alpha-linolenic acid (LA/ALA)reduces the accumulation of visceral fat mass and/or visceral adiposity, especially to reduce the accumulation of visceral fat mass and/or visceral adiposity in later life. In experiments with rodents have been given a special diet (low LA, low ratio of LA/ALA) at an early age (through a nursing mother), whereas the control group received no special power. On stage later age groups of animals were fed the same foods rich in saturated fats. Surprisingly, in rodents fed the experimental data power, revealed not only a decrease in total body fat, but also specific is some decrease in the mass of visceral fat, that is, there was a decrease visceral adiposity. This experience illustrates the effect of the present composition on the development of diseases later in life, particularly during childhood (ages 3-12), puberty (ages 13-18) and in adulthood (aged over 18).

On the other hand, it was also found that long-chain polyunsaturated fatty acids (LC-PUFA), especially n3 LC-PUFA, docosahexaenoic acid (DHA), stereonova acid (SDA), docosapentaenoic acid (DPA) and/or eicosapentaenoic acid (EPA), reduce the accumulation of visceral fat mass, at the same time, maintaining normal growth and development. Thus, the LC-PUFA is preferably included in the composition to reduce visceral adiposity and/or disorders in later life. Medium chain fatty acids (MCFA) affect the total reduction of fat in later life. Thus, MCFA preferably included in the present composition, but in limited quantities. In addition, the inclusion of MCFA is especially desirable in this mixture with a low content of LA, since it prevents the deficiency of LA.

The inventors have also found that the appointment to receive galactooligosaccharides leads to reduced insulin peak, at the same time maintaining an adequate level of glucose in the blood. As the high level and the Sulina stimulates the growth of visceral adipocytes, one example embodiment of the invention is the use of galactooligosaccharides for baby food to prevent visceral adiposity.

DETAILED description of the INVENTION

In one embodiment, the present invention relates to the use of a composition containing a lipid, protein components and digestible carbohydrates, where the lipid component causes between 35 to 55% of the total calories, the protein component provides 5 to 15% of the total calories and the digestible carbohydrates provide from 30% to 60% of the total number of calories, where the lipid component includes (i) linoleic acid (LA) and alpha linolenic acid (ALA) in a weight ratio of LA/ALA between 2 and 6; (ii) less than 14.5 wt.% LA to the total weight of fatty acids; (iii) long-chain polyunsaturated fatty acids (LC-PUFA) and, optionally, (iv) 10-50% medium chain fatty acids (MCFA), for the production of nutrient compositions assigned to a person who is not suffering from obesity, in the age of less than 36 months, to prevent the development of disease in this man, when he reaches the age above 36 months, where the disease is selected from the group including type 2 diabetes, hyperglycemia, fasting, insulin resistance, visceral adiposity, hyperinsulinemia, hypertension, cardiovascular disease, the Church is brovascular disease, arthrosclerosis, dyslipidemia, hyperuricemia, fatty infiltration of the liver, osteoarthritis and sleep apnea.

In one embodiment, the present invention relates to the use of a composition containing a lipid, protein components and digestible carbohydrates, where the lipid component causes between 35 to 55% of the total calories, the protein component provides 5 to 15% of the total calories and the digestible carbohydrates provide from 30% to 60% of the total number of calories, where the lipid component contains less than 14.5 wt.% LA to the total weight of fatty acids and has a weight ratio of linoleic acid (LA) to alpha-linolenic acid (ALA) between 2 and 6, for the production of nutritional compositions for (a) preventing and/or treating visceral adiposity and/or b) the prevention and/or treatment of accumulation of visceral fat mass to excess, where the nutrient composition is assigned to a child aged 0 to 36 months.

The present invention also relates to compositions that are assigned to a person aged less than 36 months, not suffering from obesity, where the specified composition comprises lipid, protein components and digestible carbohydrates, where the lipid component causes between 35 to 55% of the total calories, the protein component provides 5 to 15% of the total calories and the digestible carbohydrate is predostavlyaut from 30% to 60% of total calories where the lipid component includes (i) linoleic acid (LA) and alpha linolenic acid (ALA) in a weight ratio of LA/ ALA between 2 and 6; (ii) less than 14.5 wt.% LA to the total weight of fatty acids; (iii) long-chain polyunsaturated fatty acids (LC-PUFA) and, optionally, (iv) 10-50 wt.% medium chain fatty acids (MCFA), to prevent the development of disease in this man at the age of more than 36 months, where the disease is selected from the group including type 2 diabetes, hyperglycemia, fasting, insulin resistance, visceral adiposity, hyperinsulinemia, hypertension, cardiovascular disease, cerebrovascular disease, arthrosclerosis, dyslipidemia, hyperuricemia, fatty infiltration of the liver, osteoarthritis and sleep apnea.

The present invention also relates to compositions assigned to a child aged between 0 and 36 months, where the specified composition comprises lipid, protein components and digestible carbohydrates, where the lipid component causes between 35 to 55% of the total calories, the protein component provides 5 to 15% of the total calories and the digestible carbohydrates provide from 30% to 60% of the total number of calories, where the lipid component contains less than 14.5 wt.% LA to the total weight of fatty acids and has a weight ratio of linoleic acid (LA) to alpha-linolenic acid (ALA) between the 2 and 6, for the manufacture of a nutritional composition for (a) preventing and/or treating visceral adiposity and/or b) the prevention and/or treatment of accumulation of visceral fat mass to excess.

In one embodiment, the present invention relates to the use of compositions containing galactooligosaccharide and/or long-chain polyunsaturated fatty acid for the production of nutritional compositions that are assigned to man the age of 36 months, not suffering from obesity, for (a) preventing and/or treating visceral adiposity and/or b) the prevention and/or treatment of accumulation of visceral fat mass to excess.

Visceral obesity

The term "visceral obesity" refers to a condition with an increased mass of visceral fat. The term "visceral obesity" also applies to Central obesity. Visceral obesity is usually caused (accumulation of excessive visceral fat mass. Visceral fat, also known as fat in the organs, intra-abdominal fat, peritoneal fat or Central fat, normally located inside the abdominal cavity as opposed to subcutaneous fat, which is found under the skin, and intramuscular fat, which is located in skeletal muscle. Visceral fat includes otechny fat, peritoneal the initial fat and retroperitoneal adipose tissue. Stocks of visceral fat can be properly investigated using techniques produce images, such as computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound sensing. It is believed that an adult is suffering from visceral adiposity or has the mass accumulation of visceral fat to the excess, if visceral adipose tissue (VAT) is more than 100 cm2in men and 90 cm2women (Saito et al., 1999, Int J Obes Suppl 3:S226). Children usually have about 10% visceral fat mass from total fat mass. Thus, the term "visceral obesity in the child preferably refers to a situation when the mass of visceral fat exceeds about 10 wt.% by weight total fat (for example, between 10 and 20 wt.% visceral fat mass relative to the mass of total body fat). The people who came out of childhood, specifically about over 12 years of age, visceral obesity also refers to a "well rounded Apple" obesity, obesity male type, "abdominal" obesity, obesity prevailing at the waist, "body" obesity or male obesity. Waist circumference over 102 cm for adult men or 88 cm for adult women is an indicator of visceral obesity. Also as an indicator of visceral obesity may use the ratio of waist circumference to the hip. The ratio of waist circumference to hip in excess of 0.9 in men and of 0.85 in women, indicates visceral obesity. For children 3-19 years relevant limit values of waist circumference, depending on age and gender, can be found in Taylor et al 2000 Am J Clin Nutr 72:490-495. The patient is seen as suffering from visceral obesity, if its parameters correspond to one or more of the above criteria (threshold values calculated VAT (visceral adipose tissue), waist circumference, or the ratio of waist circumference to the hip). The accumulation of visceral fat mass to excess refers to the accumulation of visceral fat mass to a level corresponding to the state of visceral adiposity, and can be determined in the same manner described above for visceral adiposity.

Total body fat can be determined using DEXA (dual energy x-ray absorptiometry). The present composition preferably is assigned to a person who is not suffering from obesity, in the age of less than 36 months, preferably a person with non-redundant weight age less than 36 months. Obesity and/or overweight accordingly can be determined by the doctor. Usually incomplete child under 36 months of age has a specific gender percentile weight-growth below 95, b is more preferably below 85. Characteristic gender-specific percentiles weight growth were published by the Center for Disease Control and Prevention (CDC) in 2000.

The lipid component

In this text LA refers to linoleic acid (18:2, n6); ALA refers to alpha-linolenic acid (18:3, n3); LC-PUFA refers to long-chain polyunsaturated fatty acids containing at least 20 carbon atoms in chain fatty acids with 2 or more unsaturated bonds; DHA refers to docosahexaenoic acid (22:6, n3); EPA refers to eicosapentaenoic acid (20:5, n3); ARA refers to arachidonic acid (20:4, n6). Medium chain fatty acids (MCFA) are fatty acids and/or acyl chains with a chain length of 6, 8 or 10 carbon atoms. MCFA can also refer to the medium chain triglycerides (MCT).

The authors of the present invention found that a special composition with a low ratio of LA/ALA and LA depleted and also, optionally containing LC-PUFA and including, if desired, MCFA, prevent the occurrence of visceral adiposity. Especially, the appointment to receive the nutritional composition including (i) the ratio of LA/ALA between 2 and 6 and (ii) low LA content (<14.5 wt.% the total weight of fatty acids) and, optionally, a LC-PUFA (especially DHA)reduces visceral adiposity in later life and/or reduce the incidence of illness is any at a later age. As it turned out, MCFA reduce obesity in General. This discovery provides the opportunity to further develop the optimum composition that contains MCFA, but not in excessive amounts, i.e. between 10 and 50 wt.% the total weight of fatty acids.

The present composition comprises a lipid. LA must be present in sufficient quantities to maintain normal growth and development, but in the smallest possible quantity to prevent the development of visceral obesity. Thus, the composition contains less than 14.5 wt.% LA to the total weight of fatty acids, preferably between 5 and 14.5 wt.%, more preferably between 6 and 12 wt.%. Relative to the total dry weight of the composition the present composition preferably contains from 2 to 5 wt.% LA. For compositions in the form of liquid such as drinkable baby food, the LA content is preferably between 0.3 and 0.55 g LA per 100 ml liquid composition. The share of the LA preferably have between 4 and 8% of the total calories of this composition.

ALA must be present in sufficient quantities for healthy growth and development of the child. Therefore, the present composition preferably contains not less than 1.6 wt.% ALA based on the total weight of fatty acids, preferably between 1.6 and 5 wt.% ALA. Relative to the total dry weight of the composition the present composition of the site which preferably contains not less than 0.30 wt.% ALA, preferably between 0.3 and 1 wt.% ALA. For compositions in the form of liquid such as drinkable baby food, the ALA content is preferably not less than 50 mg ALA per 100 ml liquid composition, preferably between 50 and 150 mg ALA per 100 ml.

The weight ratio LA/ALA should be well balanced to prevent deposits of visceral fat mass (e.g., visceral obesity and diseases in later life, at the same time ensuring normal growth and development. A suitable ratio was established by the authors of the present invention. The present composition includes LA/ALA) in a weight ratio between 2 and 6, more preferably between 3 and 6, even more preferably between 4 and 5.5, more preferably between 4 and 5. The lipid component comprises less than 14.5 wt.% LA to the total weight of fatty acids and the ratio of LA/ALA from 2 to 6.

The present composition preferably contains LC-PUFA. The authors of the present invention found that LC-PUFA reduces visceral adiposity in later life. More preferably, the present composition includes n3 LC-PUFA, even more preferably EPA, SDA, DPA and/or DHA. It was found that these LC-PUFA reduce visceral adiposity. Since even low concentrations of DHA, SDA, DPA and/or EPA are effective and, given the importance of normal growth and development, the content of LC-UFA in the present composition preferably does not exceed 15 wt.% from the total fat content, preferably not more than 10 wt.%, even more preferably does not exceed 5 wt.%. The present composition preferably contains not less than 0.1 wt.%, preferably at least 0.25 wt.%, more preferably not less than 0.5 wt.%, even more preferably at least 0.75 wt.% LC-PUFA on the total weight of fat. For the same reason, the EPA content preferably does not exceed 5 wt.% from total fat, more preferably less than 1 wt.%, but is preferably not less than 0.025 wt.%, more preferably not less than 0.05 wt.% the total weight of fat. The DHA content preferably does not exceed 5 wt.%, more preferably does not exceed 1 wt.%, but is not less than 0.1 wt.% the total weight of fat. The DPA content preferably does not exceed 1 wt.%, more preferably does not exceed 0.5 wt.% the total weight of fat, but is preferably not less than 0.01 wt.% the total weight of fat. The content of SDA preferably does not exceed 0.5 wt.%, more preferably not greater than 0.25 wt.% the total weight of the fat, but not less than 0,005% wt. the total weight of fat.

As arachidonic acid (ARA, n6 PUFA) counteracts the effect of the present composition contains relatively small amounts of ARA. The ARA content preferably does not exceed 5 wt.%, more preferably does not exceed 1 wt.%, more preferably does not exceed 0.5 wt.%, even more preferred is sustained fashion does not exceed 0.25 wt.%, most preferably not greater than 0.05 wt.% the total weight of fatty acids. However, ARA plays an important role in the neurological development of the child. Due to the fact that the content of LA (n6 fatty acid) is preferably low, and the conversion of LA to ARA in children less effective, preferably not less than 0.02 wt.%, more preferably not less than 0.05 wt.%, more preferably not less than 0.1 wt.%, even more preferably not less than 0.2 wt.% on the total weight of fatty acids.

LC-PUFA, LA and/or ALA can be obtained as free fatty acids in the form of triglycerides in the form of diglyceride, in the form of monoglyceride, in the form of a phospholipid or a mixture of one or more of the above substances. The present composition preferably includes LC-PUFA in the form of a triglyceride and/or phospholipid.

Medium chain fatty acids (MCFA) are fatty acids and/or acyl chains with a chain length of 6, 8 or 10 carbon atoms. The present composition with a low content of LA and the ratio of LA/ALA mainly contains 10-50 wt.% MCFA of the total weight of fatty acids. LA is an essential fatty acid in the sense that it cannot be synthesized within the body. Since this composition has a relatively low content of LA, it is important that part of this song, LA is not turned into energy by the oxidation of fat) and still the way remained unavailable for anabolic purposes. To reduce oxidation of LA in the present compositions with a low content of LA, respectively, can be added MCFA. MCFA easily mobilized into the blood stream for long-term energy instead accumulate as fat, and thus reduce the oxidation of LA.

The authors present invention also found that MCFA contribute to the reduction of fat mass in later life. Therefore, the present composition mainly contains MCFA. However, MCFA to reduce the accumulation of fat, but as it turned out, have a less pronounced specific effect in reducing visceral fat mass relative influence of small amounts of LA and low ratio of LA/ALA. Therefore, the present composition preferably contains from 10 to 50 wt.% MCFA of the total weight of fatty acids, more preferably from 20 to 40 wt.%.

The present composition preferably contains at least one, preferably at least two, sources of lipids selected from the group comprising linseed oil (Flaxseed oil), rapeseed oil (including rapeseed oil, rapeseed oil, low erucic acid and canola oil), oil dolmetsch sage, perillae oil, oil purslane, oil cranberry, sea-buckthorn oil, hemp oil, oil, highly oleaginous sunflower, safflower oil, olive mA is lo, oil seafood, microbial oil, vegetable oil from black currant seed oil from ordinary bruise, milk fat, coconut oil and palm kernel oil. The present composition preferably contains at least one, preferably at least two, sources of lipids selected from the group including Flaxseed oil, rapeseed oil, coconut oil, high class sunflower, milk fat and oils from seafood.

Table 1 lists the desirable characteristics of the lipid component of the present composition

TABLE 1
Preferably, theMore preferablyMost preferably
LA (wt.% the total weight of fatty acids)<a 14.55-14,56-12
The weight ratio LA/ALA2-63-64-5,5
MCFA (wt.% the total weight of fatty acids)10-5010-4015-25
n3 LC-PUFA (% wt. the total weight of fatty acids)0.1 to 150,25-100,5-5

Nevereverever oligosaccharides

It is believed that one of the actions visceral fat mass is to stimulate the production of insulin, which over time can lead to decreased insulin sensitivity and other disorders, and other metabolic disorders. High levels of blood insulin stimulates glucose uptake in adipose tissue, which leads to an increase in the mass of adipose tissue. In children, high levels of insulin contribute to the increased proliferation of visceral adipocytes, at least partly, due to increased absorption of glucose.

Therefore, the present composition preferably provides a low level of insulin. The present composition preferably contains an ingredient that improves and/or maintains insulin sensitivity. It was found that nevereverever oligosaccharides (NDO), which can undergo fermentation (in particular, galactooligosaccharide), have a regulatory effect on the level of insulin in the blood and, therefore, contribute to reducing the proliferation of visceral adipocytes.

In addition, it was found that children absorb more calories when art is venom feeding compared with the situation of breastfeeding. In addition to the properties of the lipid component of the composition, as proposed in the present invention, the efficiency can also be improved by reducing calorie intake. However, limiting the dosage of the nutritional composition is almost impossible for children. The authors of the present invention found that it is preferable to enable not digested oligosaccharides in the present compositions.

Thus, the present composition preferably contains presents the lipid component and nevereverever oligosaccharides, which may be subjected to fermentation. The combination presents a lipid component and not digested oligosaccharides synergistically reduces visceral adiposity and/or prevents the development of disease in later life. Preferably, nevereverever oligosaccharides have a DP (degree of polymerization between 2 and 60. The composition preferably prevents the occurrence of resistance to insulin. Nevereverever oligosaccharide preferably selected from the group consisting of fructo-oligosaccharides (including inulin), galactooligosaccharides (including transplantological), glucooligosaccharides (including gentoo, Niger and cyclodextringlucosyl), arabinopyranoside, mannanoligosaccharides, xylooligosaccharides, focalises is haridev, arabinogalactans, glucopyranosides, galactopyranoside, oligosaccharides containing sialic acid and oligosaccharides, including uronic acid. The present composition preferably contains fructo-oligosaccharides, galactooligosaccharides and/or oligosaccharides comprising galacturonic acid, more preferably galactooligosaccharide, most preferably transplantological. In a preferred embodiment, the composition comprises a mixture of transplantationfollow and fructo-oligosaccharides. The present composition preferably contains galactooligosaccharide with DP 2-10 and/or fructo-oligosaccharides with DP 2-60. Galactooligosaccharide preferably selected from the group consisting of transplantationfollow, lacto-N-tetraone (LNT), lacto-N-neoteroi (neo-LNT), fucosyllactose, fokusirovannyi LNT and fokusirovannyi neo-LNT. In a particularly preferred embodiment, the present method includes assigning transplantationfollow ([galactose]n-glucose; where n is an integer from 1 to 60, that is, 2, 3, 4, 5, 6, ...., 59 ,60; preferably n is selected from 2, 3, 4, 5, 6, 7, 8, 9 or 10). Transplantological (TOS), for example, are sold under the trademark Vivinal™ (Borculo Domo Ingredients, Netherlands). Sugars that are part of transplantationfollow, preferably who are closely linked β-bond. Fructooligosaccharide is a NDO-chain β-linked fructose units with a DP or an average DP of 2 to 250, more preferably from 10 to 100. Fructooligosaccharide includes inulin, Levan and/or mixed type polifruktan. Particularly preferred fructooligosacharides is inulin. Fructooligosaccharide suitable for use in the compositions, is already commercially available, for example Raftiline®HP (Orafti). Oligosaccharides containing uronic acid, preferably obtained by cleavage of pectin. Therefore, the present composition preferably contains the product of the cleavage of pectin with a DP between 2 and 100. The cleavage products of pectin preferably obtained from Apple pectin, beet pectin and/or citrus pectin. The composition preferably contains transplantological, fructooligosaccharide and the product of cleavage of pectin. The weight ratio of transplantological : fructooligosaccharide : the product of cleavage of pectin is preferably 20-2 : 1 : 1-3, more preferably 12-7 : 1 : 1-2.

The composition preferably contains from 80 mg to 2 g not digested oligosaccharides per 100 ml, more preferably from 150 mg to 1.50 g, even more preferably from 300 mg to 1 g per 100 ml based On the dry weight of the composition preferably contains from 0.25 wt.% up to 5.5 wt.%, more preferably about is 0.5 wt.% up to 4 wt.%, even more preferably from 1.5 wt.% up to 3 wt.% not digested oligosaccharides.

Lactose

Preservation of insulin sensitivity can be improved by including in the composition the present composition of carbohydrates with low glycemic index, preferably lactose. Thus, the present composition preferably further comprises presents lipid component, nevereverever oligosaccharides and/or lactose. The present composition preferably contains a component breaking down carbohydrates, where lactose is at least 35 wt.%, more preferably at least 50 wt.%, more preferably at least 75 wt.%, even more preferably at least 90 wt.%, most preferably at least 95 wt.%. The present composition preferably contains at least 25 grams of lactose per 100 grams dry weight of the present composition, preferably at least 40 g lactose/100 grams.

Hydrolyzed protein

The composition preferably contains hydrolyzed casein and/or hydrolyzed whey protein. It was found that the appointment to receive the composition, where the protein is hydrolyzed casein and hydrolyzed whey protein, leads to decrease in afternoon levels as insulin, and glucose compared with the intake of the composition, sod is Rasa intact intact casein and whey protein. Elevated levels of insulin and glucose indicate the emergence of resistance to insulin in children breastfed infant formula that is believed to contribute to the development of visceral obesity in later life. The present composition preferably contains at least 25 wt.% peptides with a chain length from 2 to 30 amino acids based on the dry weight of protein. The number of peptides with a chain length from 2 to 30 amino acids may be defined as, for example, described in de Freitas et al., 1993, J. Agric. Food Chem. 41:1432-1438. The present composition preferably contains casein hydrolyzate and/or hydrolyzed whey protein, more preferably casein hydrolysate and a hydrolysate whey protein because the amino acid composition of casein cows are more similar to the amino acid composition of the protein in the milk of humans, and whey protein is easier cleaved and detected to a greater extent in the milk man. The composition preferably contains at least 50 wt.%, preferably at least 80 wt.%, most preferably about 100 wt.% the hydrolysate of the protein relative to the total weight of protein. The present composition preferably contains a protein with a degree of hydrolysis of the protein between 5 and 25%, more preferably between 7.5 and 21%, most preferably between 10 and 20%. The degree of hydrolysis is defined as the percentage the ratio of the giving of peptide bonds, destroyed by enzymatic hydrolysis, to 100% of the present total potential of peptide bonds. The present composition preferably contains 1.5 to 2.25 g of protein/100 kcal, preferably between 1.8 and 2.0 g/100 kcal.

Casein

Preferably the presence of casein, as casein increases the time of gastric emptying by education in the stomach clots, thus increasing the saturation. Since induction of saturation is very desirable, as above, the present composition preferably contains casein. If the composition is in liquid form, for example in the form of ready-to-use potable liquid, the composition preferably contains at least 0.5 g casein per 100 ml, preferably between 0.5 and 5 grams of casein per 100 ml. Preferably the composition comprises casein not less than 4 wt.% on the basis of dry weight. Casein is preferably in intact and/or non-hydrolyzed form.

Nutrient composition

The present composition is particularly suitable to provide the daily nutritional requirements of a child aged less than 36 months, especially for a child aged less than 24 months, even more preferably a child aged less than 12 months. Thus, the present composition comprises lipid, protein and carbohydrate (split carbohydrates) components, where the lipid to mponent provides 35 to 55% of total calories the protein component provides 5 to 15% of total calories and component split of carbohydrates provides 30-60% of total calories. Preferably the present composition comprises a lipid component is from 40 to 50% of the total calories, the protein component provides from 6 to 12% of total calories and component split of carbohydrates provides 40 to 50% of total calories. If the composition is in liquid form, for example in the form of ready-to-use potable liquid, the composition preferably contains from 2.1 to 6.5 g fat per 100 ml, more preferably from 3.0 to 4.0 g per 100 ml, based On the dry weight of the present composition preferably contains from 12.5 to 40 wt.% fat, more preferably from 19 to 30 wt.%.

The amount of saturated fatty acids is preferably less than 58 wt.% based on the total weight of fatty acids, more preferably less than 45 wt.%. The concentration of monounsaturated fatty acids is preferably in the range from 17% to 60% based on the total weight of fatty acids.

This composition is not breast milk of a person. The present composition preferably contains (i) a vegetable lipid and/or animal (nonhuman) fat; and/or (ii) vegetable protein and/or animal (nonhuman) milk protein. Examples of animal milk protein t is Auda whey protein milk cows and protein from goat milk. The present composition preferably does not contain an inhibitor of the protease, preferably trypsin inhibitor, chymotrypsin inhibitor or inhibitor of elastase.

The present composition preferably contains at least 50 wt.% the protein produced from nonhuman milk, based on the weight of total protein, more preferably at least 90 wt.%. Preferably the present composition contains at least 50 wt.% the protein produced from the milk of a cow, based on the weight of total protein, more preferably at least 90 wt.%. Preferably the present composition contains an acidic serum and/or sweet serum with a low concentration of glycomacropeptide. Preferably the present composition contains a protein produced from β-casein and/or α-lactalbumin. The present composition preferably contains casein and whey proteins in a weight ratio of casein : whey protein from 10:90 to 90:10, more preferably from 20:80 to 80:20. The term "protein" when used in the present invention refers to total proteins, peptides and free amino acids.

The present composition preferably is assigned to the reception in liquid form. With the aim to meet the needs of Kolaiah child composition preferably contains from 50 to 200 kcal/100 ml, more preferably from 60 to 90 kcal/100 m of the liquid, even more preferably from 60 to 75 kcal/100 ml of liquid. This caloric density ensures the optimum balance between water absorption and calories. The osmolarity of the present compositions is preferably between 150 and 420 mosmol/l, more preferably from 260 to 320 mosmol/L.

Low osmolarity is aimed at the reduction of gastrointestinal stress. Stress can cause obesity.

The composition is preferably in liquid form with a viscosity of less than 35 centipoise when measured in a Brookfield viscometer at 20°C at a shear rate of 100 s-1. The composition may be in powder form, which can be recovered water to a liquid form or in the form of a concentrated liquid, which should be diluted with water. If the composition is in liquid form, the preferred amount assigned to receive daily, is in the range of from about 80 to 2500 ml, more preferably from about 450 to 1000 ml per day.

Child

Visceral adipocytes have proliferated during the first 36 months of life, and (more limited) in puberty. Therefore, the present composition is assigned to receive the child during the first 3 years of life. It was found that the proliferation of visceral adipocytes prevails in the first 12 months of life (optimum perinatal PR is literaly adipocytes). Therefore, particularly important is the purpose of the present compositions child in this period of life. This arrangement, therefore, mainly assigned to the receiving person aged 0-24 months, more preferably to a person aged 0-18 months, most preferably to a person aged 0-12 months.

In a preferred embodiment, the present composition is assigned a premature infant in the form of infant formula and/or in the form of enrichment of the mixture of breast milk. The specific purpose of the present invention is the prevention of the disease at a later age and preferably nelechena. Therefore, the present composition preferably is assigned to the child is not suffering from obesity or childhood obesity, especially single-parent child, more preferably child suffering from overweight. The present composition preferably is assigned to the child for oral administration.

Application

The composition has a purpose (a) the prevention and/or treatment of visceral adiposity and/or b) the prevention and/or treatment of accumulation of visceral fat mass to excess. In particular, the present invention relates to a method of the prevention of visceral obesity in persons aged less than 36 months. This izobreteny who also has the purpose of preventing visceral adiposity at the age of 36 months, especially the prevention of visceral adiposity at the age of 8 years, especially over the age of 15 years. The authors of the present invention have found that the reduction of visceral adiposity in the present method, respectively, reduces the incidence and prevalence of diseases in later life, especially diseases associated with visceral obesity. The present invention also provides a method to prevent the subsequent development of disease in humans over the age of 36 months, where the disease is selected from the group including diabetes (especially type 2 diabetes), hyperglycemia, fasting, insulin resistance, hyperinsulinemia, hypertension, cardiovascular disease, visceral obesity, cerebrovascular disease, arthrosclerosis, dyslipidemia, hyperuricemia, fatty infiltration of the liver, osteoarthritis and sleep apnea (stop breathing) during sleep, by preventing visceral adiposity, and where the method includes assigning to receive the present compositions child aged less than 36 months. The present invention also provides a method of preventing diseases in humans over the age of 36 months, where the disease is selected from the group including diabetes (especially type 2 diabetes), hyperglycemia, fasting, insulin resistance, hyperinsulinemia, hypertension, ser is echno disease, visceral obesity, cerebrovascular disease, arthrosclerosis, dyslipidemia, hyperuricemia, fatty infiltration of the liver, osteoarthritis and sleep apnea (stop breathing) during sleep, where the method includes assigning to receive the present compositions child aged less than 36 months. The term "dyslipidemia" includes the following diseases: hyperlipidemia, hyperlipoproteinemia, hyperchylomicronemia, hypercholesteremia, hypoalphalipoproteinemia, Hypo-HDL(high density lipoprotein)/LDL (low density lipoprotein)-the Accademia and hypertriglyceridemia. In particular, there can be prevented the development of diabetes, visceral obesity and/or cardiovascular diseases, especially cardiovascular disease. This method is especially well applicable for the prevention of the above diseases in the pubertal period, in particular 13-18 years old and/or Mature age, particularly over the age of 18 years.

Galactooligosaccharide and/or LC-PUFA

The warning provides the use of a composition containing galactooligosaccharide and/or long-chain polyunsaturated fatty acids (LC-PUFA) for the production of nutrient compositions assigned to receive incomplete people aged less than 36 months and to prevent the development of disease when the person reaches the age above 36 months, where the specified Zab is levania selected from the group including type 2 diabetes, hyperglycemia, fasting, insulin resistance, visceral adiposity, hyperinsulinemia, hypertension, cardiovascular disease, cerebrovascular disease, arthrosclerosis, dyslipidemia, hyperuricemia, fatty infiltration of the liver, osteoarthritis and sleep apnea (stop breathing) during sleep. Galactooligosaccharide preferably selected from the group consisting of transplantationfollow, lacto-N-tetraone (LNT), lacto-N-neoteroi (neo-LNT), fucosyllactose, fokusirovannyi LNT and fokusirovannyi neo-LNT. LC-PUFA preferably represents DHA and/or EPA, preferably DHA and EPA. Nutritional composition preferably is assigned to oral intake in the form of a complete nutrient formula. Therefore, the nutritional composition preferably contains lipid, protein and carbohydrate (split carbohydrates) components, where the lipid component provides 35 to 55% of total calories, the protein component provides 5 to 15% of total calories and component split of carbohydrates provides 30-60% of total calories. The preferred number of galactooligosaccharides and/or LC-PUFA described earlier in this text. The composition preferably contains as galactooligosaccharide and LC-PUFA.

In this document and the claims, the verb enable/ hold is used in neagr the region's sense, that means that objects that are listed for the verb included, but also objects that are not listed explicitly can be included. Additionally, reference to an element in the singular does not exclude the possibility that there are more than one item, provided that the context expressly requires that the item was one and only one. Thus, the form of the singular usually mean "at least one".

EXAMPLES

Example 1: Programming effect is included in the diet fat Mature/Mature adipose tissue

Offspring of female C57/BL6 was standardized on day 2 after birth in slot 6 puppies (4 males and 2 females) female. Females had experimental diet, starting from 2 days before weaning from the breast. The lipid composition of milk mouse reflects the fat composition of the diet. After weaning from breast male mice were kept in pairs and were given the experimental diets for 42 days, when all the puppies were fed the same diet containing lard and added cholesterol. We used the following experimental diets: 1) LC-PUFA diet (butter tuna); 2) diet with low content of LA (milk fat; low oil content canola, high content Trisun 80 (high class a triglyceride in which the acid part of the 80% of butyric acid), palm oil is not available); 3) MCFA diet; 4) counter the local diet (similar amounts of canola oil, coconut oil and palm oil). Composition of fatty acids of the diet is presented in Table 2.

Table 2
The composition of fatty acids in the diet

On day 42, all mice were translated into "table diet, including fat 10 wt.% (from 3 to 5 wt.% pork fat and 0.1 wt.% cholesterol) up to 98 days. Mice were weighed twice a week. Binge eating was determined once a week during the whole experiment. To determine the body composition (i.e. fat mass (FM) and nairboi mass (FFM)was held DEXA scan (Dual energy X-ray absorptiometry) under General anesthesia at 6, 10 and 14 of the week, respectively, 42, 70 and 98 days after birth, by densitometry using the device imaging PIXImus (GE Lunar, Madison, WI, USA). At the age of 14 weeks males were euthanized, were extracted and weighed plasma, epididymal fat, perirenal fat, pancreas, liver and kidneys.

Results: during the experimental period between the groups had no effect on growth (body weight) and absorption of food (data not shown). Moreover, the development of fat mass (determined is by by DEXA) was slightly reduced in the groups, receiving MCFA, LC-PUFA and a diet low in LA, compared with controls, but not significantly on day 42 (end of the period with a modified diet). However, subsequent use of table diet (rich in saturated fatty acids) for all groups between 42 and 98 days revealed a significant difference in the composition of the body by the time the end of the experiment (day 98), see Table 3. Fat mass was reduced in animals that puppies received LC-PUFA, MCFA diet or a diet low in LA at the initial stage of life, compared with the control group. Moreover, the rations at the initial stage of life had a significant effect on the distribution of fat in the body. It was found that the ratio of subcutaneous fat:visceral fat (measured by epididymectomy and perianalnom fat heat) in adult mice on day 98 was increased by 14% in the group treated with LC-PUFA, and 32% in the group receiving the diet with low content of LA, but was not increased in the group treated with MCFA, compared with the control group, see Table 3.

Table 3
The development of fat in time in % of the total body mass, the absolute weight of the fat and the mass ratio of subcutaneous fat (epididymal) and Central (perirenal) fat day 8
DayThe control dietDiet MCFAThe diet of LC-PUFADiet with low content of LA
Fat %4219,617,116,617,1
Fat %7022,122,8a 21.524,2
Fat %9826,922,820,924,2
Visceral fat (mg)9889767172
% reduction in visceral fat98014%20%19%
The ratio of subcutaneous fat visceral fat98 7,548,358,599,92
The increase ratio (%)+11%+14%+32%

In addition, it was found that epididymal adipocytes of mice treated with dining diet, present in large amounts, large and filled with lots of fat (hyperplasia), and mice receiving a diet with low content of LA, had fewer adipocytes, which was large and filled with lots of fat, whereas the group receiving rations MCFA and LC PUFA, had a lot of cells, but small. These data suggest a different mechanism of action diet with low content of LA and diet of LC-PUFA in relation to obesity. Basal insulin levels were significantly reduced by 96 day groups who have previously received rations MCFA, LC-PUFA and low in LA, compared with the control group, although the levels of plasma glucose were similar. These data show a decrease in resistance to insulin, according to the index of the homeostatic assessment model (HOMA).

The data demonstrate that the mass of visceral fat in older age obviously reduced in the diet of LC-PUFA, and/or diet is low in LA, and/or low ratio of LA/ALA at the initial stage of life. Thus, it is concluded that this fat composition programs and/or influences the body to create more healthy fat body composition in later life.

Example 2: the Levels of glucose/insulin in the blood and nevereverever oligosaccharides

Animals and treatment adult male rats of Wistar (n=7) was administered GOS (galactooligosaccharides) filler with fibrillar structure of cellulose filler or water through the gastric cannula in 1 day. The reception was administered nutritional lump volume of 6 ml, which is approximately 50% of their daily consumption of nutritional fibers; used fiber GOS was transplantological received from Elix'or (Borculo Domo). Fiber was dissolved in water. Approximately 24 hours (on day 2) was performed oral test glucose tolerance, and for 120 min after intragastric injection of carbohydrate filler (2 g/kg body weight) were tracked postprandial curves (occurring after a meal) glucose and insulin. With this purpose were periodically taken samples of blood through the cannula in the jugular vein. Animals that received intragastric injection of water or of a solution of cellulose in water in 1 day, served as a control. As the drugs fibrous filler GOS by 50% with toali of degradable carbohydrates (mainly lactose), for correction jointly appointed two control injection of carbohydrates.

Results: pre-treatment of fibres GOS clearly reduced the amount of secreted insulin, which resulted in significantly (p<0,05) lower incremental values of area under the pharmacokinetic curve (AUC). The level of glucose in the blood was changed slightly. Pre-treatment of cellulose or water did not modify insulin secretion, see Table 4.

Table 4
The levels of insulin and glucose in rats
Pre-processingAUC for insulin (PM*30 min)AUC for glucose (mm*30 min)
Water41±769±10
Cellulose46±875±9
GOS22±474±15

Example 3: Hydrolyzed proteins have a beneficial effect on insulin sensitivity

Getting protein: intact whey protein Deminal 90 and skimmed milk powder were mixed to a ratio of 40 wt.% casein and 60 the EU.% protein whey. Hydrolyzed whey protein was obtained by hydrolysis of the drug is acidic protein whey as described in examples 1-4 in WO 0141581. The degree of hydrolysis was 15%. Hydrolyzed casein was obtained commercially as LacProdan DI-2038 (Aria Foods). Two drugs were combined in a ratio of 40 wt.% hydrolyzed casein and 60 wt.% hydrolyzed whey protein.

Methods: 20 adult male rats of Wistar (aged 10 weeks at the beginning of the experiment) were kept individually. After a 4-hour fasting period of 10 animals were fed 2 ml of the composition. In the experiment with a cross-over design (experiments separated from each other by one week) was tested with three different compositions: (I) breast milk person, (ii) 17 mg protein whey/casein and 86 mg of lactose per ml, (iii) 17 mg of hydrolyzed whey protein and hydrolyzed casein and 86 mg of lactose on ml and Then were taken and blood samples (200 μl) in chilled heparinized tubes at time points t=0, 5, 10, 15, 30, 60, 90 and 120 minutes after feeding. Then the plasma was separated by centrifugation (10 min, 5000 rpm) and stored at-20ºC until analysis. Insulin in plasma was measured using a radioimmune assay (RIA, Linco Research) according to the manufacturer's instructions with the following amendments: all volumes in the analysis were reduced in the our times. Glucose in plasma was measured oxidase-peroxidase method in the format of a 96-hole tablet (Roche Diagnostics, #1448668).

Results: peak glucose that occurs after a meal and insulin was lower in rats fed intact protein whey and intact casein than in rats fed hydrolyzed whey protein and hydrolyzed casein. The area under the curve (AUC) for insulin and glucose less in rats fed hydrolyzed whey protein and hydrolyzed casein than in rats fed intact protein whey and intact casein. Also the peak time, maximum height of the peak and AUC was decreased when using hydrolyzed proteins (table 5). The presence of hydrolyzed proteins leads to afternoon levels of glucose and insulin in the blood and kinetics, more similar to those observed in the breast milk of a person. Reduced levels of insulin and glucose indicate an increased sensitivity to insulin, which, as it is believed, contributes to the prevention of Central obesity in later life.

td align="center"> 5,9±1,6
Table 5
The influence of intact and hydrolysed proteins napoleonienne time peak the maximum peak height and area under the curve for glucose and insulin
EffectIntact proteinsHydrolyzed proteinsHuman milk
The peak time (min ± standard error)
Glucose20,0±12,711,50±2,612,0±2,4
Insulin8,3±0,88,33±1,411,7±1,2
The maximum peak height (g/l ± standard error)
Glucose0,46±1,00,31±0,070,33±0,08
Insulin1,51±0,441,11±0,201,41±0,27
AUC 30 (± standard error)
Glucose (mm*30 min)5,08±1,45,1±1,8
Insulin (PM*30 min)14,3±3,412,63±4,611,7±4,7

Example 4: Baby food

Baby food containing lipid component, providing 48% of the total calories, the protein component, providing 8% of total calories, and the component of degradable carbohydrates, providing 44% of total calories; (i) a lipid component containing (based on total fatty acids): 10 wt.% LA; 20 wt.% MCFA; 0.2 wt.% DHA, 0.05 wt.% EPA; the ratio of LA/ALA is 5.1; (ii) the splitting of carbohydrates, comprising 51 g lactose/100 grams powder; 0.36 g of galactooligosaccharides with DP 2-6 and 0.4 g of fructo-oligosaccharides with DP 7-60; (ii) the protein component, including proteins of cow's milk. The label on the packaging of this baby food indicates that the diet prevents the development at a later age one or more of the following diseases: type 2 diabetes, hyperglycemia, fasting, insulin resistance, visceral adiposity, hyperinsulinemia, hypertension, cardiovascular disease, cerebrovascular disease, arthrosclerosis, dyslipidemia, hyperuricemia, fatty infiltration of the liver, osteoarthritis and sleep apnea (stop breathing) during sleep.

1. Note the persistence of the composition, containing lipid, protein components and component digestible carbohydrates, where the lipid component provides 35 to 55% of total calories, the protein component provides 5 to 15% of total calories and the digestible component of carbohydrates provides 30-60% of total calories, where the lipid component contains less than 14.5 wt.% linoleic acid on the total weight of fatty acids, the weight ratio of linoleic acid (LA) to alpha-linolenic acid (ALA) is between 2 and 6, for the production of nutritional compositions for:
a. preventing and/or treating visceral adiposity and/or
b. prevention and/or treatment of accumulation of visceral fat mass to excess, where nutrient composition assigned to receive child aged 0 to 36 months.

2. The use according to claim 1, where the nutritional composition is used to prevent the development of disease in a specified person over the age of 36 months, where the disease is selected from the group consisting of type 2 diabetes, hyperglycemia fasting, insulin resistance, hyperinsulinemia, hypertension, cardiovascular disease, cerebrovascular disease, arthrosclerosis, dyslipidemia, hyperuricemia, fatty infiltration of the liver, osteoarthritis and sleep apnea (stop breathing) during sleep, and the child is a man m, not suffering from obesity, in the age of less than 36 months.

3. The use according to claim 1, where the composition further comprises at least one component selected from the group comprising fructooligosaccharide, galactooligosaccharide (including transplantological), casein, lactose, hydrolyzed whey protein and hydrolyzed casein.

4. The use according to claim 1, where the composition contains docosahexaenoic acid (DHA).

5. The use according to claim 1, where the composition is a liquid containing from 0.3 to 0.55 g LA per 100 ml and 50 to 150 mg ALA per 100 ml.

6. The use according to claim 1, where at least 90 wt.% from the digestible carbohydrate is lactose.

7. The use of a composition for preventing and/or treating visceral adiposity containing lipid, protein components and component digestible carbohydrates, where the lipid component provides 35 to 55% of total calories, the protein component provides 5 to 15% of total calories and the digestible component of carbohydrates provides 30-60% of total calories, where the lipid component includes (i) linoleic acid (LA) and alpha linolenic acid (ALA) in a weight ratio of LA/ALA between 2 and 6; (ii) less than 14.5 wt.% LA on the total weight of fatty acids; (iii) long-chain polyunsaturated fatty acids (LC-PUFA); and, optionally, (iv) 10-50 wt.% medium chain fatty acid is t (MCFA) for the manufacture of a nutritional composition, to introduce a person who is not suffering from obesity, in the age of less than 36 months, and to prevent the development of diseases in specified person, when he reaches the age above 36 months, where the disease is selected from the group consisting of type 2 diabetes, hyperglycemia fasting, insulin resistance, hyperinsulinemia, hypertension, cardiovascular disease, cerebrovascular disease, arthrosclerosis, dyslipidemia, hyperuricemia, fatty infiltration of the liver, osteoarthritis and sleep apnea (stop breathing) during sleep.

8. The use according to claim 7, where the composition further comprises at least one component selected from the group including fructo-oligosaccharide, galactooligosaccharide (including transplantological), casein, lactose, hydrolyzed whey protein and hydrolyzed casein.

9. The use according to claim 7, where the composition contains docosahexaenoic acid (DHA).

10. The use according to claim 7, where the composition is a liquid containing from 0.3 to 0.55 g LA per 100 ml and 50 to 150 mg ALA per 100 ml.

11. The use according to claim 7, where at least 90 wt.% from the digestible carbohydrate is lactose.

12. The use of a composition defined in claims 1 to 6 to prevent the development of diseases selected from the group consisting of diabetes, visceral obesity and/or cardiovascular for the of oleani.

13. The use of a composition defined in claims 7-12 to prevent the development of diseases selected from the group consisting of diabetes, visceral obesity and/or cardiovascular diseases.

14. The application of item 12 or 13, where the nutrient composition is assigned to a person under the age of 18 months.

15. The application of item 12 or 13, where arachidonic acid is not more than 0.5 wt.% on the total weight of fatty acids.

16. The application of item 12 or 13, where the composition contains hydrolyzed casein and/or hydrolyzed whey protein.

17. The use of a composition for preventing and/or treating visceral adiposity, containing galactooligosaccharide and/or long-chain polyunsaturated fatty acid, for the manufacture of a nutritional composition for administration to a person not suffering from obesity, in the age of less than 36 months, and to prevent the development of diseases of the specified person over the age of 36 months, where the disease is selected from the group including type 2 diabetes, hyperglycemia, fasting, insulin resistance, visceral adiposity, hyperinsulinemia, hypertension, cardiovascular disease, cerebrovascular disease, arthrosclerosis, dyslipidemia, hyperuricemia, fatty infiltration of the liver, osteoarthritis and apnea (stop breathing) during sleep.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula

and ,

where the ring X represents benzole or pyridine; R1 represents substituted alkyl; R2 represents optionally substituted aryl or optionally substituted 4-7-member monocyclic heterocyclic group or optionally substituted condensed group of heterocyclic group with the benzole ring where the substitutes of optionally substituted aryl, optionally substituted 4-7-member monocyclic heterocyclic group and optionally substituted condensed group of heterocyclic group with the benzole ring are selected from a group consisting of; (1) alkyl optionally substituted by a group selected from halogen and alkoxycarbonyl, (2) alkoxy optionally substituted by halogen, (3) halogen, (4) 4-7-member monocyclic heterocyclic group or (5) amino, optionally mono- or disubstituted alkyl, and (6) hydroxyl, R3 represents hydrogen or alkyl: R4 represents hydrogen, halogen or alkyl; R5 represents hydrogen or alkyl; R6 and R7 are identical or different, and each represents hydrogen or halogen; or pharmaceutically acceptable salt. Also, the invention refers to a IKur blocker containing the compounds described above as an active ingredient, and also to a preventive and therapeutic agent for cardiac arrhythmia and atrial fibrillation.

EFFECT: there are produced and described new compounds applicable as a IKur blocker effective for preventing or treating cardiac arrhythmia, such as atrial fibrillation.

12 cl, 13 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel crystalline forms of 3-[[3,5-dribromo-4-[4-hydroxy-3-(1-methylethyl)phenoxy]phenyl]amino]-3-oxopropanoic acid, characterised by X-ray powder diffraction pattern with principal peaks either at 2θ = 16.1 ± 0.2, 20.1 ± 0.2, 20.7 ± 0.2, and 24.2 ± 0.2, or at 2θ = 9.0 ± 0.2, 14.7 ± 0.2, 19.6 ± 0.2, 21.6 ± 0.2 and 24.3 ± 0.2. The invention also relates to methods of obtaining the disclosed crystalline forms, a pharmaceutical composition having thyroid beta-receptor agonist properties, a method for selective agonist action on thyroid beta-receptor, use of said forms to produce a medicinal agent and a method of treating mammals suffering from thyroid dysfunction associated conditions.

EFFECT: obtaining novel crystalline forms of 3-[[3,5-dribromo-4-[4-hydroxy-3-(1-methylethyl)phenoxy]phenyl]amino]-3-oxopropanoic acid, having thyroid beta-receptor agonist properties.

19 cl, 3 tbl, 7 ex

FIELD: medicine.

SUBSTANCE: invention refers to experimental medicine and can be used for developing molecular methods of treating coronary insufficiency. For this purpose, the simulated myocardial ischemia requires experimental myocardial injections of an endotheliocyte growth factor gene in the form of the phVEGF165 vector at 50-100 mcg/cm2 of an ischemic region at an area pitch of 5 mm. 2-dimethylaminoethanol is added to the vector preparation to provide more effective myocardiocyte transfection.

EFFECT: unlike peptide growth factors requiring the regular administration, the use of a gene construct with the endotheliocyte growth factor gene introduced in a single dose according to the developed method provides the intensified myocardial construct delivery and the activation of a greater number of cells involved in angiogenesis that promotes repaired perfusion in the ischemic myocardium region.

2 ex, 4 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, namely to combined drugs, and can be used for treating arterial hypertension. The drug is prepared by direct compression. A preparation with low residual humidity is more storage stable, shows high processibility and biological availability. The combined hypotensive drug contains a combination of enalapril maleate and hydrochlorthiazide as an agent, and lactose anhydride, microcrystalline cellulose, povidone, colloidal silicon dioxide, croscarmellose sodium and stearic acid salt as excipients. The optimum proportions of the components makes, wt %: The agent 11.0-18.0; Lactose anhydride 56.0-78.0; Microcrystalline cellulose 5.0-15.0; Povidone 2.0-4.0; Colloidal silicon dioxide 0.5-1.0; Magnesium stearate 0.5-1.0; Croscarmellose sodium 3.0-5.0.

EFFECT: making the drug preparation for treating arterial hypertension.

12 cl, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, pharmacology and biology and concerns application of Trecresan as an agent to decrease cholesterol esterase activity.

EFFECT: invention allows extending the range of agents used to decrease cholesterol esterase activity.

4 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted methyl-amines of general formula 1, having serotonin 5-HT6 receptor antagonist properties. In formula 1 , W is naphthalene, indolysin or quinoline; R1 is hydrogen, fluorine, chlorine, methyl; R2 is hydrogen, fluorine, methyl, phenyl, thiophen-2-yl, furan-2-yl, pyridyl, piperazin-1-yl or 4-methylpiperazin-1-yl; R3 is methyl; or W is benzene, R3 assumes the value given above; R1 is 3-Cl, R2 is 3-piperazin-1-yl or 3-(4-methylpiperazin-1-yl); or R1 is hydrogen, R2 is phenyl or pyridyl; or R1 is hydrogen, fluorine, chlorine, methyl; R2 is 4-piperazin-1-yl or 4-(4-methylpiperazin-1-yl); or W is oxazole, R3 is optionally substituted methyl; R1 is chlorine or fluorine, R2 is methyl, or R1 is hydrogen, fluorine, chlorine, methyl; R2 is piperazin-1-yl, 4-methylpiperazin-1-yl, or R1 is chlorine, fluorine or methyl; R2 is furan-2-yl, or R1 is hydrogen, fluorine, chlorine, methyl; R2 is furan-2-yl, R3 is (tetrahydrofuran-2-yl)methyl, or R1 is hydrogen, fluorine, chlorine, methyl; R2 is thiophen-2-yl, R3 is 2-methoxyethyl, or R1 is chlorine or fluorine, R2 is thiophen-2-yl, R3 is methyl.

EFFECT: compounds can be used to treat central nervous system (CNS) diseases, such as psychiatric disorders, schizophrenia, anxiety disorders, as well as for improving mental capacity, for treating obesity or for studying the molecular mechanism of inhibiting serotonin 5-HT6 receptors.

15 cl, 27 dwg, 2 tbl, 25 ex

FIELD: chemistry.

SUBSTANCE: compounds activate glucokinase and can be used to prepare medicine for treating of metabolic disorders, for lowering blood glucose level, for treating hyperglycemia, for treating IGT, for treating Syndrome X, for treating impaired fasting glucose (IFG), for treating type 2 diabetes, for treating type 1 diabetes, for delaying the progression of impaired glucose tolerance (IGT) to type 2 diabetes, for delaying the progression of non-insulin requiring type 2 diabetes to insulin requiring type 2 diabetes, for treating dyslipidemia, for treating hyperlipidemia, for treating hypertension, for lowering food intake, for appetite regulation, for for treating obesity, for regulating feeding behaviour, or for enhancing the secretion of enteroincretins. In compounds of formula , A denotes , R3 is selected from a group consisting of phenoxy and benzyloxy, each possibly substituted with one or more substitutes independently selected from R12; R12 is F, CI, Br, -CF3, -CN methyl, ethyl, isopropyl, tert-butyl, methoxy, methylthio, ethoxy, cyclopropyl-methoxy, -NHC(O)CH3 or -S(O)2-CH3; R30 is methyl, ethyl, propyl, isopropyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, methoxy, ethoxy, propoxy, butoxy, tert-butoxy, benzyloxy or cyclopropyl-methoxy, each possibly substituted with one or more substitutes independently selected from R12; R8 is methylthio, isopropylthio, ethylthio or 2-methylpropylthio, each substituted with one or more substitutes independently selected from R34; R34 is carboxy.

EFFECT: improved properties of the compound.

13 cl, 1 tbl, 242 ex

FIELD: chemistry.

SUBSTANCE: invention refers to the compounds of formula (I): where R denotes cycloalkyl, heterocyclil, aryl, alkyl-O-C(O)-, alkanoyl or alkyl where each cycloalkyl, heterocyclil and aryl does not necessarily contain from 1 to 3 substitutes chosen from the group including alkyl, hydroxy group, halogen, cyano group, alkoxy group, alkyl-O-C(O)-, amino group, mono- or disubstituted by alkyl amino group and heterocyclil, and where each alkyl-O-C(O)-, alkyl, alkoxy group and heterocyclil does not necessarily have additional 1 to 3 substitutes chosen from the group including a hydroxy group, alkyl, halogen, carboxy group, alkoxy group, alkyl-O-C(O)-, alkanoyl, alkyl-SO2-, amino group, mono- or disubstituted by alkyl amino group and heterocyclil; R2 denotes alkyl, cycloalkyl, cycloalkylalkyl- or alkoxy group where alkyl does not necessarily contain from 1 to 3 substitutes chosen from the alkoxy group or halogen; R3 denotes R8-O-C(O)-, (R8)(R9)N-C(O)-, R8-C(O)-, where R8 and R9 independently denote alkyl, cycloalkyl, aryl, arylalkyl-, cycloalkylalkyl- or nonaromatic heterocyclil where each alkyl, cycloalkyl, aryl, arylalkyl-, cycloalkylalkyl- and nonaromatic heterocyclil do not necessarily contain from 1 to 3 substitutes chosen from the group including a hydroxy group, carboxy group, alkyl-O-C(O)-, alkyl-C(O)-O- and alkanoyl; R4 and R5 independently denote hydrogen, alkyl, alkynyl, alkoxy group, cycloalkyl, arylalkyl-, cycloalkylalkyl-, heteroarylalkyl-, monoalkylamino-C(O)-, dialkylcmino-C(O)- or dialkylamino-C(O)-alkyl-, where both these alkyl groups do not necessarily form a ring and where each alkyl, alkynyl, cycloalkyl, arylalkyl-, cycloalkylalkyl- heteroarylalkyl-, monoalkylamino-C(O)-, dialkylamino-C(O)- or dialkylamino-C(O)-alkyl- do not necessarily contain from 1 to 3 substitutes chosen from the group including alkyl, hydroxy group, halogen, carboxy group and alkoxy group; R6 and R7 independently denote hydrogen, halogenalkyl, halogen, dialkylamino group, alkoxy group, halogenalkoxy group, heteroaryl or alkyl-S(O)2- where each heteroaryl does not necessarily contain from 1 to 3 substitutes chosen from alkyl; where "heterocyclil" denotes fully saturated or nonsaturated aromatic or nonaromatic cyclic group that is represented by 5- or 6-membered monocyclic ring system containing at least one heteroatom chosen from nitrogen, oxygen and sulphur atoms; "heteroaryl" denotes 5- or 6-membered monocyclic ring system containing from 1 to 4 heteroatoms chosen from N, O and S; or to their pharmaceutically acceptable salts and their optical isomers, or to mixtures of the optical isomers. The invention also refers to the method of inhibition of the specimen's CETP activity, to the way of treatment of the specimen's abnormality or disease mediated by CETP or responsive to CETP inhibition, to the pharmaceutical composition, and to application of the formula (I) compounds.

EFFECT: production of new bioactive compounds that inhibit the CETP.

10 cl, 71 ex

FIELD: chemistry.

SUBSTANCE: invention refers to new compounds of the formula (I) that are characterized by the properties of M3 muscarine receptor antagonist that is applicable in treatment or prevention of the disease or state (the abnormity of) which includes activity of the M3 muscarine receptor such as respiratory diseases. In the formula (I) A is represented by the oxygen atom or the group -N(R12)-; (i) R1 is represented by C1-C6-alkyl or the hydrogen atom; and R2 is represented by the hydrogen atom or the group -R5, -Z-Y-R5, -Z-NR9R10, -Z-NR9CO-R5 or -Z-CO2H; and R3 is absent or is represented by C1-C6-alkyl, and in this case the nitrogen atom to which it is bound is represented by tetradic nitrogen and bears a positive charge; or (ii) R1 and R2 together with nitrogen to which they are bound form heterocycloalkyl ring; the mentioned ring is displaced by the group -Y-R5 or -Z-Y-R5, and R3 is absent or is represented by C1-C6-alkyl, and in this case the nitrogen atom to which it is bound is represented by tetradic nitrogen and bears a positive charge; R4 is represented by the formula group (a), (b), (c) or (d); Z is represented by C1-C16-alkylene group; Y is represented by the link or the oxygen atom; R5 is represented by C1-C6-alkyl, aryl, phenyl condensed with C3-C6cycloalkyl, phenyl condensed with heterocycloalkyl, heteroaryl, aryl(C1-C8-alkyl)-, heteroaryl(C1-C8-alkyl)-, C3-C6cycloalkyl or heteroC3-C6cycloalkyl group; R6 is represented by C1-C6-alkyl or the hydrogen atom; n and m equal 0; R8a and R8b are independently chosen from the group consisting of aryl, phenyl condensed with heterocycloalkyl, heteroaryl, C1-C6-alkyl, C3-C6cycloalkyl; R8c is represented by -OH or C1-C6-alkyl; R9 and R10 are represented independently by the hydrogen atom, C1-C6-alkyl, aryl, phenyl condensed with heterocycloalkyl and other components mentioned in the invention formula.

EFFECT: new compounds applicable in treatment or prevention of the disease or state (the abnormity of) which includes activity of the M3 muscarine receptor such as respiratory diseases.

10 cl, 49 ex

FIELD: medicine.

SUBSTANCE: group of inventions is connected to the methods of plasm HbAlc level, delay or retardation of hyperglycemia development and delay or retardation of hyperglycemia aggravation of patient with diabetes who suffers from at least one cardiovascular disease where cardiovascular diseases are chosen of the group consisting of cardiac failure, backward heart failure, acute heart failure, ischemia, recurrent ischemia, myocardial infarction, arrhythmia, acute coronary syndrome and intermittent lameness. The patient receives effective quantity of N-(2,6-dimethylfenyl)-4-[2-hydroxy-3-(2-methoxyfenoksy)-propyl]-1-piperazine acetamide (rhanolazine) or its pharmaceutically applicable salt.

EFFECT: group of inventions ensures decrease of plasm HbAlc level in treatment of cardiovascular diseases thus reducing the number of drugs necessary for the patient.

20 cl, 8 dwg, 2 tbl, 11 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula

,

where each radical R-R5 and Y assume values given in the description, or salts thereof, which have GPR40 receptor modulating action.

EFFECT: intensification of secretion of insulin or an agent for preventing or treating diabetes, and a pharmaceutical composition based on said compounds.

17 cl, 34 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a thiazole derivative of formula 1

,

as an activator of peroxisome proliferator activated receptor δ (PPARδ), or to its pharmaceutically acceptable salts.

EFFECT: production of the pharmaceutical composition for preventing and treating arteriosclerosis or hyperlipidemia, for providing higher level of high-density protein (HDP), for preventing and treating diabetes, obesity, for strengthening muscles or endurance, for improving memory or preventing and treating dementia or Alzheimer's disease or Parkinson's disease containing such thiazole derivative.

7 cl, 3 tbl, 8 ex

FIELD: medicine.

SUBSTANCE: invention refers to conjugates of a polypeptide and an oligosaccharide or its pharmaceutically acceptable salt in which the polypeptide is conjugated to at least one oligosaccharide-spacer residues; the oligosaccharide represents a synthetic sulphated pentasaccharide residue and substantially shows affinity for antithrombine III, and the spacer shows a bond and is substantially a pharmacologically inactive flexible cross-link residue.

EFFECT: conjugates of the present invention have improved pharmacokinetic properties in comparison with appropriate unconjugated polypeptides.

13 cl, 24 dwg, 7 tbl, 28 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula I:

or pharmaceutically acceptable salts thereof, in which Q is a divalent or trivalent radical selected from C6-10aryl and heteroaryl; where said aryl or heteroaryl in Q is optionally substituted up to 3 times with radicals independently selected from halogen, C1-6 alkyl, C1-6 alkyl substituted with halogen, C1-6 alkoxy group, C1-6 alkoxy group substituted with halogen, -C(O)R20 and -C(O)OR20; where R20 is selected from hydrogen and C1-6 alkyl; and where optionally, the carbon atom neighbouring W2 can be bonded through CR31 or O with a carbon atom of Q to form a 5-member ring condensed with A and Q rings; where R31 is selected from hydrogen and C1-6 alkyl; W1 and W2 are independently selected from CR21 and N; where R21 is selected from hydrogen and -C(O)OR25; where R25 denotes hydrogen; ring A can contain up to 2 carbon ring atoms substituted with a group selected from -C(O)-, -C(S)- and -C(=NOR30)- and can be partially unsaturated and contain up to 2 double bonds; where R30 denotes hydrogen ; L is selected from C1-6alkylene, C2-6alkenylene, -OC(O)(CH2)n-, -NR26(CH2)n- and -O(CH2)n-; where R26 is selected from hydrogen and C1-6 alkyl; where n is selected from 0, 1, 2, 3 and 4; q is selected from 0 and 1; t1, t2, t3 and t4 are each independently selected from 0, 1 and 2; R1 is selected from -X1S(O)0-2X2R6a, -X1S(O)0-2X2OR6a, -X1S(O)0-2X2C(O)R6a, -X1S(O)0-2X2C(O)OR6a, -X1S(O)0-2X2OC(O)R6a and -X1S(O)0-2NR6aR6b; where X1 is selected from a bond, O, NR7a and C1-4alkylene; where R7a is selected from hydrogen and C1-6alkyl; X2 is selected from a bond and C1-6alkylene; R6a is selected from hydrogen, cyanogroup, halogen, C1-6alkyl, C2-6alkenyl, C6-10aryl, heteroaryl, heterocycloalkyl and C3-8cycloalkyl; where said aryl, heteroaryl, cycloalkyl and heterocycloalkyl in R6a is optionally substituted with 1-3 radicals independently selected from hydroxy group, halogen, C1-6alkyl, C1-6alkyl substituted with a cyano group, C1-6alkoxy group and C6-10aryl-C1-4alkoxy group; and R6b is selected from hydrogen and C1-6alkyl; R3 is selected from hydrogen, halogen, hydroxy group, C1-6alkyl, C1-6alkyl substituted with halogen, C1-6alkyl substituted with a hydroxy group, C1-6alkoxy group, C1-6alkoxy group substituted with halogen, -C(O)R23 and -C(O)OR23; where R23 is selected from hydrogen and C1-6alkyl; R4 is selected from R8 and -C(O)OR8; where R8 is selected from C1-6alkyl, heteroaryl, C3-8cycloalkyl and heterocycloalkyl; where said heteroaryl, cycloalkyl or heterocycloalkyl in R8 is optionally substituted with 1-3 radicals independently selected from halogen, C1-6alkyl, C3-8cycloalkyl and C1-6alkyl substituted with halogen; R5 is selected from hydrogen, C1-6alkyl substituted with a hydroxy group, and a C1-6alkoxy group; heteroaryl denotes a monocyclic or condensed bicyclic aromatic ring complex containing 5-9 carbon atoms in the ring, where one or more ring members are heteroatoms selected from nitrogen, oxygen and sulphur, and heterocycloalkyl denotes a saturated monocyclic 4-6-member ring in which one or more said carbon atoms in the ring are substituted with a group selected from -O-, -S- and -NR-, where R denotes a bond, hydrogen or C1-6alkyl. The invention also relates to pharmaceutical compositions containing said compounds, and methods of using said compounds to treat or prevent diseases or disorders associated with GPR119 activity, such as obesity, type 1 diabetes, type 2 sugar diabetes, hyperlipidemia, type 1 autopathic diabetes, latent autoimmune diabetes in adults, type 2 early diabetes, child atypical diabetes, adult diabetes in children, malnutrition-associated diabetes and diabetes in pregnant women.

EFFECT: improved properties of compounds.

27 cl

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula

,

and pharmaceutically acceptable salts and solvates thereof, in which R1 is an optionally substituted alkyl or similar, R2 is a group of formula: -Y-R5, where Y is -O- or S; R5 is a substituted alkyl (the substitute is an optionally substituted cycloalkyl or similar), a branched alkyl or similar; R4 is hydrogen or C1-10 alkyl; R3 is a group of formula: -C(=O)-Z-R6, where Z is -NR7- or -NR7-W-; R6 is an optionally substituted cycloalkyl or similar; R7 is hydrogen or C1-10 alkyl, W is C1-10 alkylene; X is =N- provided that a compound in which R2 is 2-(4-morpholino)ethoxy, 2-, 3- or 4-pyridylmethoxy, 1-methylpiperidinyl-2-methoxy, benzyloxy or 4-substituted benzyloxy is excluded; and R3 is N-(1-adamantyl)carbamoyl, N-(2-adamantyl)carbamoyl and N-(3-noradamantyl)carbamoyl. Said compound is an 11β-hydroxysteroid dehydrogenase type 1 inhibitor. The invention also relates to a pharmaceutical composition containing said compound as an active ingredient.

EFFECT: improved properties of the compound.

23 cl, 72 ex

FIELD: medicine.

SUBSTANCE: group of inventions is connected to the methods of plasm HbAlc level, delay or retardation of hyperglycemia development and delay or retardation of hyperglycemia aggravation of patient with diabetes who suffers from at least one cardiovascular disease where cardiovascular diseases are chosen of the group consisting of cardiac failure, backward heart failure, acute heart failure, ischemia, recurrent ischemia, myocardial infarction, arrhythmia, acute coronary syndrome and intermittent lameness. The patient receives effective quantity of N-(2,6-dimethylfenyl)-4-[2-hydroxy-3-(2-methoxyfenoksy)-propyl]-1-piperazine acetamide (rhanolazine) or its pharmaceutically applicable salt.

EFFECT: group of inventions ensures decrease of plasm HbAlc level in treatment of cardiovascular diseases thus reducing the number of drugs necessary for the patient.

20 cl, 8 dwg, 2 tbl, 11 ex

FIELD: medicine.

SUBSTANCE: invention is referred to the area of medicine, namely to hematology, endocrinology and cardiology and can be used for decease of spontaneous RBC aggregation in patients with abdominal obesity. To do that the metformin infusion are performed with the background of hypocaloric diet and dosed static and dynamic physical exercises. Physical exercises include morning hygiene gymnastics, therapeutic gymnastics, single physical exercises during the day, daily swimming for no less than 30 minutes a day in the middle of the day. Metformin is given in the dose 500 mg twice a day. The treatment shall be performed for 1 month.

EFFECT: method provides for normalization of spontaneous RBC aggregation within 1 month, bringing it down on the level close to that in healthy people and thus decreasing the risk of thrombotic complications in patients with abdominal obesity.

2 ex, 1 dwg

FIELD: medicine.

SUBSTANCE: invention refers to new compounds of formula (I) where X is carboxylic acid, carboxylates, carboxylic anhydride, diglyceride, triglyceride, phospholipid, or carboxamides, or to any their pharmaceutically acceptable salt. The invention particularly refers to (4Z, 7Z, 10Z, 13Z, 16Z, 19Z)-ethyl 2-ethyldocosa-4,7,10,13,16,19-hexanoate. The invention also refers to a food lipid composition and to a composition for diabetes, for reducing insulin, blood glucose, plasma triglyceride, for dislipidemia, for reducing blood cholesterol, body weight and for peripheral insulin resistance, including such compounds. Besides, the invention refers to methods for treating and/or preventing diabetes, dislipidemia, peripheral insulin resistance, body weight reduction and/or weight gain prevention, insulin, blood cholesterol, blood glucose and/or plasma triglyceride reduction.

EFFECT: higher clinical effectiveness.

61 cl, 4 tbl, 16 dwg, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to oxadiazolidinone compounds presented by following formula (I), or to their pharmaceutically acceptable salts, (symbols in the presented formula represent the following values, R1: -H, R0: lower alkyl, Rz: the same or different from each other, and each represents -H or lower alkyl, L: *-CH2-O- or *-CH2-NH-, where the symbol * in L represents binding with the ring A and a substitution position in the group L in the ring B represents the 4-position, the ring A: benzole, the ring B: benzole or pyridine, R2; the same or different respectively, and each represents -halogen or -R0, n: 0 or 1, R3: phenyl which can be substituted by a group selected from the group G3, The group G3: halogen, -R0, halogen-lower alkyl, -ORz, -CON(Rz)2, -CON(Rz)-heteroring group, -O-S(O)2-R0, -O-lower alkylene-ORz, -O-lower alkylene-O-COR2, -O-lower alkylene-N(RZ)2, -O-lower alkylene-N(Rz)CO-Rz, -O-lower alkylene-CO2Rz, -O-lower alkylene-CON(Rz)2, -O-lower alkylene-CON(Rz)-(lower alkyl substituted by the group-ORz), -O-lower alkylene-SR0, -O-lower alkylene-cycloalkyl, -O-lower alkylene-CON(Rz)-cycloalkyl, -O-lower alkylene-heteroring group and -O-lower alkylene-CON(Rz)-heteroring group, where lower alkylene in the group G3 can be substituted by halogen or -ORz, and cycloalkyl and the heteroring group in the group G3 can be substituted by the group selected by the group G1, The group G1: halogen, cyano, -R0, -ORz, -N(RZ)2, -S-R0, -SO2-R0, -SO2N(Rz)2, -CO-R2, -CON(Rz)2, -CON(Rz)-lower alkylene-OR2, -N(Rz)CO-Rz, oxo, -(lower alkylene which can be substituted by the group -ORz)-aryl, heteroring group and lower alkylene-heteroring group where aryl and the heteroring group in the group G1 can be substituted by the group selected from the following group G2, the group G2: halogen, cyano where the heteroring group means a group containing a ring selected from i) a monocyclic 5-7-members, saturated or unsaturated heteroring containing 1 to 3 heteroatoms selected from O, S and N, ii) a bicyclic heteroring in which the heterorings selected in i) mentioned above are ring-condensed where the condensed rings can be the same or different, and iii) the bicyclic heteroring in which the heteroring selected in i) mentioned above is condensed with a benzoic ring or 5-7-members cycloalkane, R4: -H. The invention refers to a pharmaceutical composition, to application of the compounds under cl.1, as well as to a method for preventing and/or treating diabetes.

EFFECT: making new biologically active compounds representing GPR40 agonist, an agent stimulating insulin secretion and/or an agent for preventing and/or treating diabetes.

9 cl, 27 ex, 138 tbl

FIELD: chemistry.

SUBSTANCE: present invention refers to the compound 5-[3-[(2S)-1-(difluoromethoxy)-propane-2-yl]-oxy-5-[(5-methylpyrazin-2-yl)-carbamoyl]]phenoxy]-N,N-dimethyl-pyrazine-2-carboxamide. The invention also refers to a pharmaceutical composition, and also to application of the compound under cl.1.

EFFECT: making the new biologically active compounds showing GLK (glucokinase) activator activity.

5 cl, 6 ex, 2 tbl, 2 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a thiazole derivative of formula 1

,

as an activator of peroxisome proliferator activated receptor δ (PPARδ), or to its pharmaceutically acceptable salts.

EFFECT: production of the pharmaceutical composition for preventing and treating arteriosclerosis or hyperlipidemia, for providing higher level of high-density protein (HDP), for preventing and treating diabetes, obesity, for strengthening muscles or endurance, for improving memory or preventing and treating dementia or Alzheimer's disease or Parkinson's disease containing such thiazole derivative.

7 cl, 3 tbl, 8 ex

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