Method of stimulating intestinal barrier integrity after nonvaginal delivery

FIELD: medicine.

SUBSTANCE: invention relates to feeding of newborn babies delivered by Caesarian section. Claimed is change of composition which contains long-chain polyunsaturated fatty acid and, at least, one substance, selected from group, consisting of (a) nucleotide and (b) nucleotide precursor, selected from group consisting of nucleotides, purine bases, pyridine bases, ribose and deoxyribose for obtaining composition for introduction to newborn baby delivered by Caesarian section, for treatment and/or prevention of infection, diarrhea, intestine phlegmon, allergy, atopic eczema, asthma, allergic rhinitis and/or allergic conjunctivitis. Composition can also be used to improve intestinal maturation, reduction of intestinal permeability and/or for treatment of disorders associated with intestinal barrier, in newborn baby delivered by Caesarian section. Introduced to newborn baby composition is not human breast milk.

EFFECT: invention makes it possible to improve intestinal flora of newborn babies, delivered by Caesarian section.

12 cl, 5 tbl, 6 ex

 

The scope of the invention

The present invention relates to a method of feeding and treatment of infants born by caesarean section.

Prior art

Babies have at birth immature intestine. After birth, the neonatal gastrointestinal tract is rapid development and maturation, including mucus formation and maturation and sustainable closure of places of penetration of allergens, toxins and pathogens. In human milk, there are several factors that enhance the development of the intestine.

Permeable immature intestinal barrier plays a role in the acquisition of a phlegmon of intestinal infections, diarrhoea and atopic diseases, including food Allergy. Properly ripen the intestine, especially in combination with a healthy intestinal flora, reducing the incidence of infections, strengthening the immune system, reducing the incidence of food allergies, and/or other atopic diseases, and/or reduce incidence of diarrhoea, constipation and/or abscess of intestine.

Intestinal permeability decreases faster in children breastfed than infants on artificial feeding. However, breastfeeding is not always possible.

International application WO 2004112509 picavet composition for the stimulation of the nature of the maturation of the intestinal barrier, similar to that observed with breastfeeding, and can improve the maturation of the intestinal barrier, for example, during the neonatal stress.

International application WO 2005122790 describes a method of promoting the integrity of the barrier in a mammal by administration to the mammal of a composition containing eykozapentaenovuyu acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (ARA) and at least two different oligosaccharide.

European patent EP 1549158 describes the composition with the formula for newborns, which contain from 3.2 mg/l up to 15.4 mg/l CMP; 1.8 mg/l to 11.0 mg/l of UMP; 1.8 mg/l to 8.0 mg/l of GMP; from 0.1 mg/l to 2.2 mg/l of IMP; and from 2.5 mg/l to 13.2 AMP.

International application WO 03043445 describes recycled baby food that was prepared with (a) oil, (b) nucleotides, (c) oils and nucleotides.

Natren® produces probiotic product Life Start®that is specifically designed for newborns and suitable for babies born by caesarean section. Life Start® is made withBifidobacterium infantis.Because the product Life Start® contains only a singleBifidobacteria,the benefit for the newborn is very limited.

The invention

The authors of the present invention have found that babies born by caesarean section, have intestinal flora that differs from isichei flora of newborns, born through the birth canal. Partially, babies born by caesarean section have a lower degree of intestinal colonizationBifidobacteriaand have less diversity of intestinal floraBifidobacteriumrelative species than infants born through the birth canal, partially missingBifidobacterium breve, Bifidobacteriumlongum, BifidobacteriuminfantisandBifidobacteriumbifidum.The authors of the present invention have found, moreover, that the intestinal flora of infants born by caesarean section, has a lower content ofBifidobacteria,compared with the intestinal flora of infants born by vaginal delivery.Additionally, they discovered that the intestinal flora of infants born by caesarean section, has a high content of (unwanted)Escherichia coli6 weeks after the birth of.

Healthy and fully developed gastro-intestinal flora plays an important physiological effects. An important aspect is that it reduces the frequency of cases (gastrointestinal) infections. Because babies born by caesarean section, need healthy flora, prevention of infection is especially important for these children. These children are normally born in the hospital at risk of development Pat the gene infections due to nosocomial bacteria. Additionally, the reduction in the development of a healthy intestinal flora leads to rapid colonization by pathogenic bacteria, in comparison with the situation when the gastrointestinal tract of newborns seeded parent bacteria, obtained from vaginal and intestinal flora of the mother. To prevent bacterial translocation or bacterial translocation (endo - or Exo-) toxins on intestinal barrier these (nosocomial) pathogens, it is extremely important to improve and/or accelerate intestinal maturation in neonates born by caesarean section. Improving the maturation of the intestinal barrier and/or barrier permeability in neonates born by caesarean section, in addition, it decreases the incidence of cellulitis gut, food allergies and/or other atopic diseases.

The inventors have found that the barrier function of children born by caesarean section, disturbed, and found that long-chain polyunsaturated fatty acids (LC-PUFA) and/or nucleotide improve maturation and integrity of the intestinal barrier and/or have anti-inflammatory effects in children born by caesarean section. In addition, the LC-PUFA promote adhesion of bacteria producing lactic acid on mucous membranes. Therefore, the present invention relates to the use of compo is icii, containing LC-PUFA and/or nucleotide, which, in particular, is designed to (a) reduce the frequency of infections by increasing the permeability of the intestinal barrier and/or acceleration of maturity, (b) reduce the frequency (food) allergies and/or other atopic diseases by increasing the permeability of the intestinal barrier and/or acceleration of maturity; (C) moisturizing or softening processes phlegmon of the intestine, which otherwise can additionally increase the permeability of the intestinal barrier, and/or (d) improvement of flora by increasing the colonization of bacteria that produce lactic acid on mucous in neonates born by caesarean section.

In an additional aspect of the present invention can be implemented by combining these active ingredients in the nutritional composition. Without large expenses such compositions can be administered to the neonate born by caesarean section.

A detailed description of the preferred embodiments

The present invention provides use of a composition containing (i) long-chain polyunsaturated fatty acid (LC-PUFA); and/or (ii) at least one selected from the group consisting of (a) nucleotide and (b) predecessor nucleotide selected from the group consisting of nucleosides, purine OS is Avani, pyridine bases, ribose and desoxyribose, to obtain a composition for administration to the newborn, born by caesarean section. In another aspect, the present method provides the use of a composition containing (i) long-chain polyunsaturated fatty acid (LC-PUFA); and/or (ii) at least one selected from the group consisting of (a) nucleotide and (b) predecessor nucleotide selected from the group consisting of nucleosides, purine bases, pyridine bases, ribose and desoxyribose to obtain a composition for : (i) treatment and/or prevention of disorders in newborns born by caesarean section, and/or (ii) promoting health in newborns born to by caesarean section.

The present invention also provides a method of feeding a newborn baby, born by caesarean section, which includes the introduction of this newborn composition containing (i) long-chain polyunsaturated fatty acid (LC-PUFA) and/or (ii) at least one selected from the group consisting of (a) nucleotide and (b) predecessor nucleotide selected from the group consisting of nucleosides, purine bases, pyridine bases, ribose and desoxyribose.

Cesarean section

Caesarean section (C-section) is a surgical procedure which, when a newborn is born through an incision made in the abdominal wall of the mother, and then through the wall of the uterus. A caesarean section is usually performed when it is safer for the mother or baby, than birth through the birth canal. In another case, a woman may choose cesarean section more likely than normal delivery path.

Long-chain polyunsaturated fatty acids

Throughout this description, the composition used in the method according to the present invention, often referred to as “the present composition”. The present composition preferably contains long-chain polyunsaturated fatty acids (LC-PUFA). LC-PUFA are fatty acid where the acyl chain has a length of from 20 to 24 carbon atoms (preferably 20 or 22 carbon atoms) and where the acyl chain contains at least two unsaturated relationship between carbon atoms in the acyl chain. More preferably the present composition comprises at least one LC-PUFA selected from the group consisting of eicosapentaenoic acid (EPA, 20:5 n3), docosahexaenoic acid (DHA, 22:6 n3), arachidonic acid (ARA, 20:4 n6), docosapentaenoic acid (DPA, 22:5 n3). For EPA, DHA and ARA was found to be effective reduction of the permeability of the intestinal tight connections (see example 2). Reduced Prony is aImost dense connections reduces the frequency of infection and/or reduces the passage of allergens and/or reduces the passage of bacterial (endo - or Exo-) toxins. In addition, the connection LC-PUFA, preferably EPA, DHA and/or ARA in the present composition improves the permeability of the intestinal barrier, which is extremely important for children born by caesarean section, in addition, these children have less developed intestinal flora and, therefore, slow ripening of the intestinal barrier. LC-PUFA additionally have anti-inflammatory effects and help the adhesion of the bacteria that produce lactic acid on mucous membranes, through this stimulation develops healthy flora, which, furthermore, advantageous for use in neonates born by caesarean section.

Since low concentrations of ARA, DHA, DPA and/or EPA always effective in reducing the permeability of the tight connection, the content of LC-PUFA in the present composition, which is preferably the nutritional composition preferably does not exceed 15% of the mass. from the contents of fat, preferably less than 10 wt. -%, even more preferably, not more than 5% of the mass. Preferably, the present composition contains at least 0.1% wt., preferably, at least 0.25% of mass., more preferably, at least 0.5% wt., even more preferably, at least about 0.75% of the mass. LC-PUFA content of total fat. For the same reason, the EPA content preferably does not exceed 5% of the mass. all W the RA, more preferably, does not exceed 1 wt. -%, but is preferably at least 0.025% wt., more preferably, at least 0.05% wt. all fat. The DHA content preferably does not exceed 5 wt. -%, more preferably, does not exceed 1 wt. -%, but represents at least 0.1% of the mass. all fat. Since it was found that ARA partially effective in reducing the permeability of the tight connection, the present composition contains a relatively high concentration, preferably at least 0.1% wt., even more preferably at least 0.25% of mass., most preferably at least 0.35% of the mass. ARA of total fat. The ARA content preferably does not exceed 5 wt. -%, more preferably 1 wt%. all fat. When the present enteral composition comprises ARA, EPA and DHA, it is advantageously added to balance the action of ARA, for example, reduces the potential Pro-inflammatory action of ARA metabolites. Excess ARA metabolites can cause inflammations. Therefore, the present composition preferably contains ARA, EPA and DHA, in which the weight ratio of ARA/DHA is preferably above the 0.25, preferably above 0.5, more preferably above 1. The proportion of ARA/DHA is preferably less than 25, more preferably below 15. The weight ratio of ARA/EPA PR is doctitle from 1 to 100, more preferably from 5 to 20.

In order to resemble human milk as much as possible and to reduce the side effects of high doses of LC-PUFA, the present composition contains a LC-PUFA, preferably not exceeding 3% of the mass. from the content of total fat. The content of n3 (omega-3) LC-PUFA, preferably below 1% of the mass. from the content of total fat. n6 (omega-6) LC-PUFA, preferably below 2 wt%. from the content of total fat. The ARA content preferably below 1% of the mass. from the content of total fat. The weight ratio of EPA/DHA is preferably 1 or less.

LC-PUFA can be represented in the form of free fatty acids in the form of triglycerides in the form of diglyceride, in the form of monoglyceride, in phospholipid form or as a mixture of one or more of the above, preferably in the form of triglycerides. The present composition preferably contains at least one of ARA and DHA in phospholipid form.

Nucleotides

In a preferred embodiment, the present composition comprises the nucleotide and/or precursor nucleotide selected from the group consisting of nucleosides, purine bases, pyridine bases, ribose and desoxyribose. More preferably the composition comprises the nucleotide. The nucleotide is preferably in monophosphate, diphosphate or trifosfatnogo form, more preferably, is ribono what leotides. The nucleotides can be Monomeric, dimeric or polymeric (including RNA and DNA). The nucleotides are preferably present as free acid or in salt form, more preferably, monosodium salt. The connection of the nucleotide in the present composition improves the permeability of the intestinal barrier and/or maturation, which is extremely important for children born by caesarean section, because these children have less developed intestinal flora and, therefore, slower ripening of the intestinal barrier. Preferably, the composition comprises one or more selected from the group consisting of citizen-5'-monophosphate (CMP), uridine-5'-monophosphate (UMP), adenosine-5'-monophosphate (AMP), guanosine-5'-monophosphate (GMP) and inosine-5'-monophosphate (IMP) and/or their salts, in particular their monosodium salts, more preferably at least 3 selected from the group consisting of CMP, UMP, AMP, GMP and IMP and/or their salts, in particular their monosodium salt. The reduction of nucleotide diversity may, in addition, to improve barrier permeability.

Preferably the composition contains from 5 to 100 mg, more preferably from 10 to 25 mg nucleotides per 100 g dry weight of the present composition. Nucleotides, in addition, stimulate the immune system, thereby again increasing protection against high loads of enteric pathogens, such asE.coli.

Suppose the equipment composition contains from 1 to 20 mg, more preferably from 3 to 12.5 mg CMP 100 g dry weight of the composition. Preferably the composition contains from 1 to 20 mg, more preferably from 2 to 9 mg UMP 100 g dry weight of the composition. Preferably the present composition contains from 0.5 to 15 mg, more preferably from 1.5 to 8 mg AMP per 100 g dry weight of the present composition. Preferably the composition contains from 0.2 to 10 mg, more preferably from 0.6 to 3 mg GMP 100 g dry weight of the composition. Preferably the present composition contains from 0.5 to 10 mg, more preferably from 1.3 to 5 mg IMP 100 g dry weight of the composition.

Preferably the present composition comprises both (i) LC-PUFA and (ii) a nucleotide and/or precursor nucleotide selected from the group consisting of nucleosides, purine bases, pyridine bases, ribose and desoxyribose, in addition, the combination of these components unexpectedly improves the barrier function of the gut immune system and/or intestinal flora, for example, it is assumed synergistic effect.

Nevereverever oligosaccharides

The present composition preferably contains nevereverever oligosaccharides, which are fermented to organic acids (preferably, lactic acid, butyrate, propionate, and/or acetate) and stimulate the growth of bacteria, producing intestinal lactic acid (hereinafter, referred to as the nevereverever sugars”). Preferably the growth ofBifidobacteriaandLactobacillistimulated. Increased content ofBifidobacteriaandLactobacillistimulates the formation of healthy intestinal flora. Additionally, the formed organic acids stimulate the production of mucus and, in addition, reduces the permeability of the intestinal barrier in neonates born by caesarean section (see example 3, below). Nevereverever oligosaccharides also reduce the effect of LC-PUFA and/or nucleotide of the present composition, as the joint introduction not digested oligosaccharides with LC-PUFA and/or nucleotide slows down the absorption of the LC-PUFA and/or nucleotides in the small intestine by means of rollover and/or reduce the effects of LC-PUFA and/or nucleotide in the gut. Advantageously, this composition contains nevereverever oligosaccharides, preferably with a degree of polymerization (DP) from 2 to 250, more preferably from 2 to 100, more preferably from 2 to 10.

The present composition preferably contains nevereverever oligosaccharides with degree of polymerization (DP) less than 60, more preferably below 40, even more preferably below 20, most preferably below 10. Short chain not digested oligosaccharides provides improved lactate or acetate production, stimulates barrier permeability in newborn, born the s by caesarean section. Nevereverever oligosaccharides preferably not absorbed or only partially digested in the small intestine by the action of acids or digestive enzymes present in the digestive tract of a (small intestine and oral cavity) and are fermented by intestinal flora of man. For example, sucrose, lactose, maltose and maltodextrins are considered digestible.

Preferably the present composition contains at least one nevereverever oligosaccharide selected from the group consisting of fructo-oligosaccharides (including inulin), not digested dextrins, galactooligosaccharides (including transplantological), xylooligosaccharides, arabinopyranoside, arabinogalactans, glucooligosaccharides (including cyclodextrins and gentiopicroside), chitooligosaccharides, glycogenolysis, galactopyranoside, mannanoligosaccharides, focalisation, oligosaccharides the galacturonic acid oligosaccharides guluronic acid, oligosaccharides mannurone acid, oligosaccharides iduronovoy acid, oligosaccharides Rybarikova acid, oligosaccharides glucuronic acid, and mixtures thereof, more preferably of fructo-oligosaccharides, galactooligosaccharides (including transplantological), focalisation and ha oligosaccharides is acharonova acid and mixtures thereof, even more preferably transplantationfollow.

Presents nevereverever oligosaccharide preferably selected from the group consisting of galactooligosaccharides and fructo-oligosaccharides (e.g., inulin). Preferably at least 50 wt%. presented not digested oligosaccharides have a degree of polymerization of from 2 to 60. In particular, the preferred implementation of the present composition contains at least galactooligosaccharide and fructo-oligosaccharides. Galactooligosaccharide preferably contain saccharides with a DP of 2 to 10. Fructo-oligosaccharides preferably contain saccharides with a DP of 2 to 60. Preferably, galactooligosaccharide contain beta-communication, as in the case of oligosaccharides of human milk.

In the preferred embodiment the present composition comprises oligosaccharides the galacturonic acid. Oligosaccharides the galacturonic acid of the invention successfully reduces the adhesion of pathogens to epithelial cells of the intestine, thereby reducing colonization (nosocomial) of pathogenic microorganisms in the gut of neonates born by caesarean section. In addition, oligosaccharides the galacturonic acid of the present invention stimulate the production of healthy intestinal flora and are fermented, which leads to output the Wu intestinal organic acids and decrease intestinal pH, which limits the growth of (nosocomial) pathogenic microorganisms. The joint introduction of the oligosaccharides galacturonic acid, consequently, furthermore, it improves the protection of neonates born by caesarean section, from infections due to undeveloped barrier function and/or underdeveloped intestinal bacterial flora.

The term "oligosaccharide the galacturonic acid"used in the present invention preferably refers to oligosaccharides, in which at least 50% of the monosaccharide units in the oligosaccharide are the galacturonic acid. The present composition preferably contains the oligosaccharide galacturonic acid with a DP of 2 to 250, preferably from 2 to 50, more preferably from 2 to 20. Oligosaccharides the galacturonic acid used in the invention, preferably prepared from pectin, pectate and/or polygalacturonic acid. Oligosaccharide the galacturonic acid is preferably derived from pectin. Preferably pectin oligosaccharide obtained by hydrolysis and/or beta-elimination of fruit pectin and/or vegetable pectin, more preferably from Apple, citrus pectin and/or sugar beet pectin, more preferably Apple, citrus and/or pectin sugar beets are processed at least by liati. Preferably Lisa the pectin and/or oligosaccharide the galacturonic acid derived from bacterial production.

In a preferred embodiment, at least one of the end units of ascorbic acid oligosaccharide the galacturonic acids have a double bond, which is preferably between position4and C5end unit ascorbic acid. The double bond effectively protects against attachment of pathogenic bacteria to intestinal epithelial cells. This is useful for babies born by caesarean section. Preferably at least 5%, more preferably at least 10%, even more preferably at least 25% limit units ascorbic acid oligosaccharide the galacturonic acid is unsaturated unit of ascorbic acid. Each individual oligosaccharide the galacturonic acid preferably contains only one unsaturated unit ascorbic acid, preferably less than 50% of end units ascorbic acid is unsaturated end unit ascorbic acid (i.e. contains a double bond).

The present composition preferably contains from 0.01 to 10 g oligosaccharide the galacturonic acid with a DP of 2 to 250 per 100 g dry weight of the entire composition, more preferably from 0.05 to 6 g, even more preferably from 0.2 to 2, Preferably the present composition contains from 0.01 to 10 g of oligosaccharide to galacto is about acid with a DP of 2 to 25 per 100 g dry weight of the nutritional composition, more preferably from 0.05 to 6 g, even more preferably from 0.2 to 2, Short chain oligosaccharides the galacturonic acids are more effective and/or better suited for inclusion in the present composition.

Preferably, the composition comprises (i) galactooligosaccharide, (ii) fructo-oligosaccharides and (iii) the oligosaccharides galacturonic acid. This combination is partially suitable for the protection of infants born by caesarean section, because it provides optimal stimulation forBifidobacteriaand/orLactobacilliand reduces the adhesion of pathogenic microorganisms and reduces colonization and/or adhesion potential pathogenic bacteria such asE.coli.

Bacteria that produce lactic acid

The present composition preferably contains bacteria that produce lactic acid as the living and the dead. Dead bacteria may, for example, be obtained by inactivation of live bacteria by heat treatment and/or ultrasonic treatment. Live lactic acid bacteria mainly include to stimulate rapid colonization of the intestinal tract of newborns. Bacteria that produce lactic acid, preferably equipped with a mono - or mixed culture of live microorganisms. The present composition preferably contains from 102up to 1013Colonie prasouda particles (cfu) of bacteria, producing lactic acid, per gram dry weight of the present composition, preferably from 102up to 1012cfu, more preferably from 105up to 1010cfu, most preferably from 104up to 5×109cfu.

Preferably the present composition comprises bacteria of the genusLactobacillusand/orBifidobacterium.Preferably the composition contains at least oneBifidobacterium,selected from the group consisting ofB.longum, B.breve, B.infantis, B.catenulatum, B.pseudocatenulatum, B.adolescentis, B.animalis, B.gallicum, B.lactis B.bifidum,more preferably, at least oneBifidobacteriumselected from the group consisting ofB.breve, B.infantis, B.bifidum, B.catenulatum, B.longum,even more preferably, at least oneBifidobacterium,selected from the group consisting ofB.breveandB.longum,most preferablyB.breve.Preferably the composition comprises at least two different species, subspecies or strains ofBifidobacterium. The present composition preferably contains at least one, more preferably at least two, more preferably at least three, most preferably at least four different species ofBifidobacterium.The present composition preferably contains at least one, more preferably at least two, more preferably at least three, most preferably at minicamera four different strains of Bifidobacterium.Typically, the purpose of pre-cooked combinations will increase the variety and/or number of microorganisms in the gut of neonates born by caesarean section. This has a beneficial effect on newborns, providing various health benefits.

Preferably the present composition containsLactobacillus,selected from the group consisting ofL.casei, L.reuteri, L.paracasei, L.rhamnosus, L.acidophilus, L.johnsonii, L.lactis, L.salivarius, L.crispatus, L.gasseri, L.zeae, L.fermentumandL.plantarum,preferablyL.casei, L.paracasei, L.rhamnosus, L.johnsonii, L.acidophilus, L.fermentumand, more preferably,L.paracasei.Even more preferably, this composition containsBifidobacterium breveand/orLactobacillus paracasei,because the growth of these bacteria is reduced in neonates born by caesarean section. In addition, increased biological diversity will have a stimulating effect on the health of the baby born by caesarean section.

Formula

The present composition preferably is introduced enterline, more preferably orally. This song is the formula for newborns. The present composition is preferably a synthetic formula, which is obtained by mixing the various ingredients. This composition is not natural milk mammals, such as breast what elocom person. This composition can advantageously be used as a comprehensive nutrition for newborns. The present composition preferably contains lipid, protein and carbohydrate, and preferably is introduced as a liquid food. The term "liquid food"used in the present invention, contains dry food (e.g., powders), which is provided with preparation instructions, where specified, how to mix mix dry food with a suitable liquid (e.g. water).

The present composition preferably provides the nutrition of the newborn, and contains a lipid component, a protein component and a carbohydrate component. The lipid component preferably provides from 5 to 50% of the total calories, the protein component preferably provides from 5 to 50% of all calories and carbohydrate component preferably provides 15 to 90% of all calories. The present composition preferably is applied as a formula for newborns, in which the lipid component provides 35 to 50% of the total calories, the protein component provides from 7.5 to 12.5% of all calories and carbohydrate component provides from 40 to 55% of all calories. To calculate the % of total calories for the protein component is taken into account all the energy provided by proteins, peptides and amino acids.

Preferably the lipid component contains a combination of at least one lipid is, selected from the group consisting of vegetable and animal fats and at least one type of oil selected from the group consisting of fish, animal fat, vegetable, fungal oil, oil of algae and bacterial oil. Preferably, the lipid composition comprises at least 12 mg/100 kcal of α-linolenic acid (ALA). Preferably the lipid composition has a mass./mass. the proportion of linoleic acid (LA) and ALA from 5 to 15, more preferably from 5 to 10. Preferably the amount of TRANS fatty acids less than 4% of the mass. from all of lipids. The high content of TRANS fatty acids is compromised intestinal barrier.

The protein component used in the present composition preferably contains at least one selected from the group consisting of proteins of animal other than humans (such as protein, milk protein and egg protein), vegetable protein (such as soy protein, wheat protein, rice protein, potato protein and protein legumes), free amino acids and mixtures thereof. The source of nitrogen derived from cow's milk, in particular cow's milk proteins such as casein and whey proteins are particularly preferred. Preferably the protein component contains the intact proteins, more preferably intact proteins bovine serum and/or intact proteins in cow's what about casein. This composition is suitable for use to reduce allergic reactions in infants, protein formulas for newborns preferably selected from the group consisting of hydrolyzed milk protein (for example, hydrolyzed casein and/or hydrolyzed whey protein), vegetable protein and/or amino acids. The application of these gidrolizirovanny proteins additionally weakens allergic reaction in a newborn. The application of these gidrolizirovanny proteins advantageously improves the absorption of dietary belkovo component immature intestine of newborns born by caesarean section.

Preferably the composition contains digestible carbohydrates. Digestible carbohydrates used in the present compositions are preferably selected from the group consisting of sucrose, lactose, glucose, fructose, syrup solids corn starch and maltodextrins, and mixtures thereof, more preferably lactose.

Irregular bowel movements (e.g., constipation, insufficient stool, diarrhea) are a major problem in some children, including infants born by caesarean section. It was found that stool can be reduced by the introduction of LC-PUFA in the liquid food. The present composition preferably has the Osma is lalmost from 50 to 500 mOsm/kg, more preferably from 100 to 400 mOsm/kg With this in mind, it is important that the liquid food was not excessive caloric value, however, provided enough calories to raise the subject. Therefore, liquid food preferably has a caloric value of from 0.1 to 2.5 kcal/ml, even more preferably caloric value of from 0.5 to 1.5 kcal/ml, most preferably from 0.6 to 0.8 kcal/ml

Application

The present invention provides a method for feeding infants born by caesarean section, including the introduction of the present composition consisting of (i) LC_PUFA and/or (ii) nucleotide and/or precursor nucleotide selected from the group consisting of nucleosides, purine bases, ribose and deoxyribose, the specified infant.

The present invention also provides a method i) stimulate the health of the newborn, born by caesarean section, and/or (ii) treatment and/or prophylaxis of disorders in infants born by caesarean section, including the introduction of the present compositions newborn. Disorders, preferably selected from the group consisting of intestinal disorders caused by low content of bifidobacteria in the intestinal flora. Preferably the violation is chosen from the group consisting of infection and atopicheskogo the disease. The present composition is preferably administered to the neonate born by caesarean section in the first year of life, preferably within 3 months after birth, even more preferably within 100 hours, more preferably within 72 hours, most preferably within 48 hours after birth.

The present composition can preferably be used to stimulate the maturation of the intestinal barrier; increased permeability of the intestinal barrier and/or stimulation of the immune system. The present method preferably includes the stages of (a) mixing (i) food or pharmaceutically acceptable liquid; and (ii) a dry composition, where the dry composition (ii) contains the LC-PUFA and/or nucleotides, preferably LC-PUFA and nucleotides; and stage b) introducing the composition obtained in stage a), babies born by caesarean section.

Introduction the composition containing LC-PUFA and/or nucleotide, leads to increased translocation (nosocomial) pathogens, such asE.coli, otherGram-negative species belonging to the generaAeromonas, Klebsiella, Enterobacter, Pseudomonas, ProteusandAcinetobacter andGram-positive species, such asEnterococcus, Staphylococcus, Streptococcus, BacillusandClostridium,viruses and fungi, preferablyEscherichia coli (E.coli).Therefore, the present composition before occhialino used in the method of treatment and/or prevention of infection and/or diarrhea in infants born by caesarean section, and this method includes the introduction of this song newborns born by caesarean section. In a preferred embodiment, the present composition is used for treatment and/or prophylaxis of infections caused byEscherichia coliAeromonas, Klebsiella, Enterobacter, and/or Pseudomonasmore preferably(E.coli).

Introduction the present compositions containing LC-PUFA, and/or nucleotides and/or precursors of nucleotides leads to reduced translocation of allergens along the intestinal barrier. Therefore, the present composition preferably used in the method of treatment or prevention of Allergy, preferably food Allergy, atopic eczema (e.g. atopic dermatitis), asthma, allergic rhinitis and/or allergic conjunctivitis in neonates born by caesarean section, this method includes the introduction of specified composition newborns born by caesarean section. Preferably, the present composition is used for the treatment and/or prevention of atopic dermatitis.

In addition, the introduction of this composition enhances the immune system. Therefore, the present composition comprising LC-PUFA, and/or nucleotides and/or precursors of nucleotides, favorably used is in the treatment and/or prevention of systemic infections and/or inflammation in newborns, born by caesarean section. In a preferred method of the present composition is used for treatment and/or prevention of necrotizing enterocolitis.

In the present description and in the claims, the verb "includes" and its combinations are used in their non-limiting sense to indicate that the objects following the word are included, but objects not specifically mentioned are not excluded. In addition, the form of the singular does not exclude the possibility that there is more than one item, unless the context clearly indicates that there is one and only one element. The singular form, thus, usually means "at least one".

Examples

Example 1: Molecular characterization of the intestinal microbiota in neonates born by vaginal delivery, compared to born by cesarean section

In the present study, the influence of birth (birth through caesarean section against birth through the birth canal) on the intestinal microbial composition on the third day of life were investigated using PCR amplification with species-specific primers for ten species ofBifidobacterium,three species ofRuminococcusand one of the formBacteroides.

Microbial DNA was extracted and analyzed according to the but Favier et al., Environ Environ 2002; 68: 219-226 and Satokari et al., Appl. Environ. Environ. 2001; 67: 504-513; Satorkari et al. System Appl. Environ. 2003; 26: 572-854.

The results of theBifidobacteriumand other genera, found in faeces samples from 21 of the newborn after caesarean section received on the 3rd day of life, are presented in table 1.

Table 2 represents theBifidobacteriumother species found in samples of faeces from 21 of the newborn after birth through the birth canal, received on the 3rd day of life. There is no special indicator for speciesB.dentium, B.angulatum, B.lactis, Ruminococcus bromii, Ruminococcus callidusandRuminococcus obeum,which were observed in the faeces of infants born by caesarean section, as well as in the faeces of infants born through the birth canal.

/tr> tr>
Table 1
Infants born by cesarean section
Novo
Born
den
nye
B.
breve
B.
infantis
B.
bifidum
B. catenu-
latum group
B.
adolescentis
B.
longum
B.
gallicum
Bacteroides fragilis
1--------
2-----++--
3--------
4--------
5------- -
6--------
7--------
8--------
9--------
10------++-
11--------
12--------
13--------
16--------
17--------
18--------
19--------
20--------
21--------
22--------
23--------
(-) no amplification; (+/-) weak amplification; (+) positive amplification;
(++) strong amplification

It can be concluded that the microbial flora of neonates born by caesarean section, differs from the microbial flora of neonates born through the birth canal. Not only the number of bifidobacteria and other genera quantitatively much lower, but also the species level of the flora of neonates born by caesarean section, is less diverse. AsBifidobacteriumis a dominant genus in the flora of the newborn, these results can be generalized, as fewer intestinal bacteria and less diversity of gut flora in infants born by caesarean section, this uninhabited gut more susceptible to colonization (nocosomial) pathogens.

These results are indicative for the useful application of the composition and method of the present invention, for example : the b-feeding infants, born by caesarean section, to reduce the effects of enteric pathogens and promotes healthy intestinal flora and, therefore, prevents infection, promotes a healthy immune system and stimulates intestinal maturation, particularly in neonates born by caesarean section.

Table 2
Neonates born through the birth canal
NOVO
BORN
DEN
NYE
B.
breve
B.
infantis
B.
bifidum
B. catenu-
latum group
B.
adolescentis
B.
longum
B.
gallicum
Bacteroides fragilis
1A-+---++--
2A+/-- ++++-++--
3A---+----
4A+/---++++--
5A+/--++++-++++-
6A--+/-++-++--
7a-- +/-++++---
8A++++-+++---
9a---++++--
10A++--++---
11a++-++++-++-+
12A++ ++-++-+
13A+/---+-+--
16A---++-+--
17A+/--++-+--
18a+/--++-+--
19a+- -+-+--
20A---+-+--
21A---++++--
22A-+-++-+--
23a+-++++-+--
(-) no amplification; (+/-) weak amplification; (+) positive amp is eficacia;
(++) strong amplification

Example 2: Effect of LC-PUFA on barrier integrity

Monolayers (MS) cell lines the intestinal epithelium T were incubated in luminale Department with various polyunsaturated fatty acids, 100 μm ARA (arachidonic acid; 5,8,11,14-eicosatetraenoic acid), DHA (CIS-4,7,10,13,16,19-docosahexaenoic acid), EPA (eicosapentaenoic acid) or control palmitic (16:0) acid (Palm) (Sigma, St. Louis, USA) at 0, 24, 48 and 72 hours. The function of the epithelial barrier was determined by measuring transepithelial resistance (TER, ASM2) volt-ohmmeter (EVOM; World Precision Instruments, Germany) and permeability for 4 KD FITC dextran (paracellular permeability marker, Sigma, USA).

The effect of fatty acids (100 μm) on spontaneous permeability barrier after 72 hours of incubation are presented in table 3. Table 3 shows that ARA, EPA and DHA LC-PUFA reduce excessive molecular isolation and improve epithelial resistance. In contrast, the control palmitic acid had the opposite effects, i.e. the deterioration of the permeability barrier. These results indicate the advantages of the use of EPA, DHA and ARA and, in particular, ARA in the composition of the invention and for use in the method according to the invention, i.e. a method for improving the permeability barrier in neonates born by caesarean section. Also g is MMA-linolenic acid (GLA) showed a positive effect on resistance permeable basal barrier and excessive selection.

Table 3
Ingredient (LC-PUFA)Excessive releaseResistance (TER)
Control791090
Palmitic acid161831
DHA721574
ARA281816
EPA651493

Example 3: Effect of LC-PUFA on the intermediate IL-4 barrier gap

Monolayers (MS) cell lines the intestinal epithelium T were incubated in the presence of IL-4 (2 ng/ml, serosal compartment, Sigma, USA) with or without polyunsaturated fatty acids ARA and DHA, GLA, EPA, or control palmitic acid (10 μm or 100 μm, mucosal compartment, Sigma, St. Louis, USA). Cells were pre-incubated with ARA, DHA, EPA, or palmitic acid for 48 hours prior to incubation with IL-4. Co-incubation of PUFA and palmitic acid with IL-4 continued other 48 hours, the average whole culture and EXT the file was changed every 24 hours. The function of the epithelial barrier was determined by measuring transepithelial resistance (TER) and permeability, as described in example 2.

The effect of ARA, DHA, EPA and palmitic acid (100 μm) of the barrier breach associated with IL-4, presented in table 4. Table 4 shows that ARA, DHA and EPA LC-PUFA inhibit increased excessive separation occurring by IL-4. In contrast, palmitic acid had a harmful effect and reduced barrier breach, compared with the control. These results are indicative for the advantageous application of ARA, DHA and EPA in clinical and infant formulas to prevent or restore the barrier breach associated with IL-4, i.e. as occurs in food allergies or allergies animal milk. These results are indicative of the benefits of using EPA, DHA and ARA and, in particular, ARA in the composition corresponding to the present invention and for use in the method corresponding to the present invention, especially in the treatment and/or prevention of Allergy, atopic eczema, asthma, allergic rhinitis and/or allergic conjunctivitis in neonates born by caesarean section.

Table 4
<> Ingredient (LC-PUFA)Excessive release of IL-4IL-4 resistance (TER)
Control582374
Palmitic acid777321
DHA271547
ARA218636
EPA228539

Example 4: flora of neonates born by cesarean section

Bifidobacterial content in the faeces of infants born by caesarean section, was determined. The percentage of all kind ofBifidobacteriumto all the bacteria in the first week was 4.3% of neonates born by caesarean section (n=44), as against 19.8% in neonates born through normal vaginal delivery (n=28). The percentage ofE. coliwas 11,8% after 6 weeks, when infants were fed a normal diet (see table 5).

Table 5
Newborn Bifidobacteriathe first week (%)E. coli6 week (%)
Birth vaginal delivery19,8
To-section4,811,8

These results indicate the desirability of the introduction of these LC-PUFA, and/or nucleotides and/or nucleotide precursors babies born by caesarean section.

Example 5: a Method of feeding infants born by cesarean section

Within two days after birth by caesarean section newborn impose nutrient composition, which contains (per liter):

energy value 672 kcal; protein 14 g; serum: the proportion of casein 60:40; fat 36 g; carbohydrate 73 g; vitamin a 500 μg RE; mixed natural carotenoids 35 µg RE; vitamin D3 12 mcg; vitamin E 12 mg; vitamin K1 45,0 mcg; vitamin .sub.1 (thiamine) 400 mcg; vitamin .sub.2 (Riboflavin) 1000 mcg; vitamin .sub.6 (pyridoxine) 400 mcg; vitamin .sub.12 (cyanocobalamin) of 2.0 mcg; Niacin 4,1 mg; folic acid 120 mcg; Pantothenic acid 2800 mcg; Biotin 18 mcg; vitamin C (ascorbic acid) 86 mg; choline 100 mg; Inositol 33 mg; taurine 67 mg, calcium 510 mg; phosphorus 290 mg; magnesium 50 mg; iron 7,0 is g; zinc is 4.9 mg; manganese 84 mcg; copper 330 mcg; iodine 100 mcg; sodium 170 mg; potassium 740 mg; chlorine 460 mg and 14 mcg selenium; where the fat content includes 0,65% of the mass. LC-PUFA based on all fatty acids, including 0,35% of the mass. ARA, 0.05% wt. EPA and 0.2% of the mass. DHA, in addition, containing 3.6 g transplantological received Elix''or™ (Borculo Domo Ingredients, Netherlands), and 0.4 g of fructo-oligosaccharides obtained RaftilineHP™ (Orafti Active Food Ingredients, Belgium), and approximately 20 mg of nucleotides (approximately 6.4 mg CMP, approximately 4 mg UMP, approximately 6 mg AMP, approximately 1.4 mg GMP and approximately 2.4 mg IMP).

1. The use of a composition containing
(i) long-chain polyunsaturated fatty acid (LC-PUFA); and (ii) at least one selected from the group consisting of (a) nucleotide and (b) predecessor nucleotide selected from the group consisting of nucleosides, purine bases, pyridine bases, ribose and deoxyribose; to obtain compositions for the introduction of a baby born by caesarean section, for the treatment and/or prevention of infection, diarrhea, phlegm bowel, allergies, atopic eczema, asthma, allergic rhinitis and/or allergic conjunctivitis, and/or to improve intestinal maturation, decrease intestinal permeability and/or for treating disorders associated with intestinal barrier, the baby born through kosarevschena, where the composition is not breast milk of a person.

2. The use of claim 1, wherein the composition further comprises at least one nevereverever oligosaccharide selected from the group consisting of fructans (including inulin, fructo-oligosaccharides, not digested dextrins, galactooligosaccharides (including transplantological), xylooligosaccharides, arabinopyranoside, arabinogalactans, glucooligosaccharides (including cyclodextrins and gentiopicroside), chitooligosaccharides, glycogenolysis, galactopyranoside, mannanoligosaccharides, focalisation, galacturonic oligosaccharides, oligosaccharides guluronic acid, oligosaccharides mannurone acid, oligosaccharides iduronovoy acid, oligosaccharides Rybarikova acid, oligosaccharides glucuronic acid and mixtures thereof.

3. The use according to claim 1, in which the composition contains transplantological and/or fructo-oligosaccharides.

4. The use according to claim 1, in which the composition contains oligosaccharides the galacturonic acid.

5. The use according to claim 1, where LC-PUFA selected from the group consisting of eicosapentaenoic acid, docosahexaenoic acid and arachidonic acid.

6. The use according to claim 1, in which the composition contains from 0.1 to 15 wt.% LC-PUFA by weight of the total grease composition.

7. PR is the application according to claim 1, in which the composition contains less than 3 wt.% LC-PUFA by weight of the total fat in composition;
A. omega-3 LC-PUFA below 1 wt.% from the content of total fat;
b. omega-6 LC-PUFA below 2 wt.% from the contents of fat; and
C. arachidonic acid below 1 wt.% from the content of total fat.

8. The use according to claim 1, in which the composition contains at least one nucleotide selected from the group consisting of citizen-5'-monophosphate, uridine-5'-monophosphate, adenosine-5'-monophosphate, guanosine-5'-monophosphate, inosine-5'-monophosphate and sodium salt of one of the previously mentioned nucleotide.

9. The use according to claim 1, in which the composition contains from 5 to 100 mg nucleotides per 100 g dry weight of the composition.

10. The use of claim 1, wherein the composition further comprises at least one bacterial species belonging to the genus Bifidobacterium or Lactobacillus.

11. The use of claim 1, wherein the lipid component provides 5 to 50% of the total calories, the protein component provides 5 to 50% of all calories, and the carbohydrate component provides from 15 to 90% of all calories.

12. The use according to claim 1, in which treatment involves the introduction of a composition prepared by mixing (I) food or pharmaceutically acceptable lipid; and (II) a dry composition, where the dry composition II contains long-chain polyunsaturated fatty acid (LC-PUFA); and, hence, is her least one selected from the group consisting of (a) nucleotide and (b) predecessor nucleotide selected from the group consisting of nucleosides, purine bases, pyridine bases, ribose and desoxyribose.



 

Same patents:

FIELD: food industry.

SUBSTANCE: invention relates to food industry and deals with alimentation of children born by cesarean section. One proposes application of a composition including indigestible oligosaccharides to produce a composition for treatment and/or prevention of diseases with children born by cesarean section. The disease is selected from the group including asthma, allergy, infection and atopic dermatitis. Indigestible oligosaccharides content in the composition is 0.5 - 75 g per 100 g of dry weight of the composition. Alternatively the composition may include at least 5 wt % of indigestible oligosaccharides, at least 1 wt % of oligosaccharide consisting of uronic acid remains in terms of dry weight of the composition while total weight of indigestible oligosaccharides is 0.1 - 10 g per portion. Alternatively the composition may content 5-100 mg of nucleotides per 100 g of dry weight of the composition. Alternatively the composition may include 102 - 1013 CFU of bacteria per 1 g of dry weight of the composition.

EFFECT: invention allows to improve intestine maturation, enhance intestinal barrier and so to improve systemic condition of children born by caesarean section as well as promotes prevention and/or treatment of infection and other diseases with children born by caesarean section.

18 cl, 3 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula in which R1 and R2 independently denote C1-6alkyl; R4 denotes phenyl, substituted with trifluoromethyl if necessary; X denotes hydrogen or methyl; and Y denotes -C(O)R, where R denotes C1-6alkyl; or Y denotes -P(O)(OR5)2, where R5 denotes hydrogen or C1-6alkyl; or pharmaceutically acceptable salts thereof. Said compounds are prodrugs of adenosine A2B receptor. The invention also relates to a pharmaceutical composition which is an adenosine A2B receptor antagonist based on the compound of formula I.

EFFECT: formula I compounds and the pharmaceutical composition can be used in treating different diseases in mammals, such as gastrointestinal disorders, immunological disorders, allergic disorders, neurological disorders, cardiovascular disorders and diseases associated with cell hyperproliferation.

13 cl, 1 tbl, 15 ex

FIELD: medicine, veterinary science.

SUBSTANCE: group of inventions concerns veterinary. A method for improving stool quality in animals consists in regulating the balance of metabolised cations and metabolised anions consumed by an animal in good supply for improving stool quality. A method of changing stool frequency in the animal includes regulating the balance of metabolised cations and metabolised anions consumed by the animal in good supply for changing stool frequency. The composition for changing stool quality and/or frequency in animals contains at least one component chosen from the group including metabolised cations, and at least one component chosen from the group including metabolised anions where the balance of metabolised cations and metabolised anions is regulated by an amount changing stool quality and/or frequency in animals.

EFFECT: group of inventions allows maintaining normal functioning of intestines in animals.

22 cl, 1 tbl, 1 ex

FIELD: veterinary.

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EFFECT: therapeutic efficiency makes 100%.

1 tbl, 4 ex

FIELD: medicine; veterinary science.

SUBSTANCE: cerebrolysin dosed 1 ml once a day within 3-4 days is injected intramuscularly to an affected animal.

EFFECT: high effectiveness.

1 tbl

FIELD: medicine.

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EFFECT: invention ensures more efficient treatment of diarrhea syndrome in case of irritate bowels syndrome in women.

6 cl, 10 ex

FIELD: medicine; veterinary medicine.

SUBSTANCE: medical product contains polyvinylpyrolidone, Furacilinum, glucose, Acidum ascorbinicum and sodium hypochlorite at the certain component proportion.

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2 tbl, 2 ex

FIELD: medicine; pharmacology.

SUBSTANCE: invention concerns a combination for proliferative disease treatment which contains antidiarrheal agent and epothylon derivative of formula (1) or epothylon derivative, method of diarrhoeia management, associated with epothylon introduction of formula (1), pharmaceutical composition, trade packing and medical product, including antidiarrheal agent and epothylon derivative.

EFFECT: compositions have improved efficiency.

9 cl, 6 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to antagonists of adenosine A2B receptors and their using in treatment of mammals in different pathological states, such as digestive, immunological, neurological disorders and cardiovascular diseases caused both hyper-proliferation of cells and their apoptosis and similar disorders. Also, invention relates to methods for synthesis of these compounds and pharmaceutical composition containing thereof. The aim of the present invention is use of compounds of the general formulae (I) and (II) for preparing pharmaceutical composition possessing antagonistic activity with respect to adenosine A2B receptors wherein radical values are given in the invention description.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

41 cl, 12 sch, 35 ex

FIELD: medicine.

SUBSTANCE: means has 0.001-0.05 mg of Ramozetron Hydrochloride as daily dose or equivalent molar quantity of Ramozetron or its other pharmaceutically permissible salt as active ingredient.

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12 cl

FIELD: medicine, pharmaceutics.

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EFFECT: inclusion of magnesium oxide into composition increases SAMe-para-toluolsulfonate stability, inositol reduces SAMe-para-toluolsulfonate hygroscopicity and contributes to its soothing and antidepressant action.

27 cl, 41 tbl, 7 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to oncology, and can be used for clinical effectiveness control in children with neuroblastomas. That is ensured by neo-adjuvant combination cytostatic therapy with peripheral vein blood sampling prior to and after each course of chemotherapy. Blood is examined for plasminogen and plasmin activity to calculate the relation of the first to the second. If the value increased after chemotherapy, a therapeutic clinical effect is predicted. If the value decreased or remained unchanged throughout two courses of chemotherapy, the absence of effect is predicted that is a basis for changing the cytostatics to provide an adequate treatment.

EFFECT: method provides assessing cancer invasiveness, its invasive and metastatic potential, detecting the patients with an expected therapeutic effect, good prognosis and the patients with no effect who require timely correction of anticancer therapy to provide prolonged and improved quality of life of the patients.

2 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds of general formula or to its pharmaceutically acceptable salts, where W is cycloalkyl; Y is hydrogen or pharmaceutically acceptable saccharide of formula, or Z is hydrogen; Q is a substitute chosen from a group consisting from and each B, E, G, R, T and M is hydrogen.

EFFECT: invention refers to methods for preparing the compounds (A) and their salts, to the based pharmaceutical composition for treatment of cancers and the associated diseases, as well as to application of said compounds and their salts in making pharmaceutical preparations for prevention and treatment of cancers.

15 cl, 1 tbl, 26 ex

FIELD: medicine.

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1 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to leprology, and can be applied for etiopathogenetic treatment of liver affection in leprosy patients. For this purpose simultaneously with specific anti-leprous therapy introduced is hepatoprotector heptral (S-adenozyle-L-methyonine). Specific anti-leprous therapy includes course introduction of dapson in dose 100 mg daily and riphampicine in dose 600 mg 1 time per month during 6 months with following interval in 1 month. Heptral is introduced in dose 400 mg twice per day in the morning and at lunch time perorally during two weeks.

EFFECT: claimed combined simultaneous introduction of medications in said regimen provides etiotropic and pathogenetic impact on disease, making it possible to realise correction of functional liver malfunctions, as well as to provide adequate protection from action of damaging factors.

4 ex

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SUBSTANCE: there is offered application of 5'-methylthyoadenosine (MTA), or its pharmaceutically acceptable salt, a prodrug for preparing a medicine for treating an autoimmune diseases where said medicine delays the beginning of outbreaks in an individual suffering multiple sclerosis (MS), or slows down the progression of MS (progressing phase) in an individual suffering MS, and a related method.

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8 cl, 6 dwg, 2 tbl

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7 cl, 5 ex, 1 tbl

FIELD: medicine.

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EFFECT: such combination of active components leads to the improved disposition profile.

14 cl, 1 ex

FIELD: medicine.

SUBSTANCE: group of inventions concerns medicine and covers normalisation of sleep/wakefulness cycle in a mammal, and also to increasing its cognitive function. It involves introduction of therapeutically effective amount of the compound chosen from the group including cytosine, cytidine, cytidine monophosphate, cytidine triphosphate, deoxycytidine monophosphate, deoxycytidine diphosphate or deoxycytidine triphosphate, cytidine diphosphate - choline, cytidine diphosphate sodium choline, uridine, uridine triphosphate, uridine diphosphate, uridine monophosphate and triacetyluridine. Said mammal does not suffer from insomnia.

EFFECT: offered methods reduce asthenia or fatigue during a day, improve sleep quality, besides, they can be used in treatment of somnipathies, including sleep apnea, periodic limb movements, a restless leg syndrome, narcolepsy and somnolency problem, or in increasing cognitive functions in the sleep deprived patients.

18 cl, 3 dwg

FIELD: medicine.

SUBSTANCE: application of the oxidised ATF form (o-ATF) as the antiangiogenic pharmacological agent, a therapeutic preparation for treatment of the tumours, including o-ATF with antitumoral substance and a therapeutic preparation for treatment of the atherosclerotic processes, containing o-ATF with antiatherosclerotic substances is offered. The agent is applicable for treatment of diseases, in whose beginning or advance the angiogenesis, such as diseases of eyes, atherosclerotic processes or tumours is involved.

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6 cl, 2 dwg, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, namely to neurology, and can be used for increasing a level of synaptic proteins in a nerve cell or a brain cell in a subject. That is ensured by introduction a combination of agents to the specified subject, namely omega-3 fatty acid and/or omega-6 fatty acid in a combination with uridine or choline salts.

EFFECT: versions of the method provide the increased level of synaptic proteins in the nerve cell, including the brain cell that can be used for correction of age-related memory disorders.

15 cl, 11 dwg, 7 tbl, 11 ex

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