Immunity-stimulating baby food

FIELD: medicine, pharmaceutics.

SUBSTANCE: nutritional and pharmaceutical composition in form of baby food contains fat, protein and carbohydrate components and includes milk serum and casein with weight ratio of casein to serum from 1:1 to 1:2.4. They contain, at least: 3 g of arginine per 100 g of protein, from total content of fatty acids: 10 wt % of linoleic acid, 1 wt % of alpha-linoleic acid, one long-chain polyunsaturated fatty acid, selected from group, consisting of docosahexaenic, arachidonic and eicosapentaenoic acid, to 25 wt %, at least one polyunsaturated fatty acid and 2-12 g of indigestible oligosaccharides with polymerisation degree from 2 to 100 per 100 g of dry weight of said composition, as well as neutral and acidic oligosaccharides, containing units of uronic acid. Pharmaceutical composition is applied in treatment and/or prophylaxis of inflammatory disease, diarrhea, eczema and/or atopic dermatitis. Prevention of allergy or diarrhea is performed by introduction of composition to child enterally or perorally.

EFFECT: inventions ensure stimulation of immune system maturing and development in babies of intestine and intestinal flora, similar to flora, obtained during breast feeding, optimal feeding, prevents penetration of allergens into general blood circulation and reduces risks associated with feeding with baby's formula based on milk serum.

17 cl, 4 tbl, 3 ex

 

The present invention relates to a nutritional or pharmaceutical composition comprising a fat component, a protein component and a carbohydrate component, whey and casein, as well as the application of the specified composition.

Breastfeeding is optimal for the development of the baby and protect him from infections. However, not all babies can get breast milk. Therefore continue to aim to create a formula that mimics the function of the female breast milk. In addition to the required similarity of the compositions of baby food and breast milk are also particularly desirable to reproduce the protective effect of breast milk. It is shown, for example, that breast milk has a protective effect against infections and allergic reactions.

In the famous children mixtures the ratio of casein and whey is approaching this ratio in breast milk as possible. It is believed that this ratio determines the optimal growth of the baby. However, there are still some disadvantages associated with the use of ruminant animals as a source of protein whey. These compounds with a predominance of whey protein do not provide optimal protection from infections. The use of such infant formula leads to a delay in development of the intestinal flora of the infant compared with young people who nzami, breastfeeding, especially during the first three to four weeks of life. Flora of infants receiving mixed with a predominance of whey protein, contains almost the same bacterial genera, as the flora of infants who are breastfed, however, the number of beneficial bacteria is reduced in infants receiving mixed with a predominance of whey protein compared with infants who are breastfed. Moreover, the flora of infants receiving a mixture containing mainly whey proteins derived from cow's milk, contains an increased number of pathological bacteria, such as clostridia and enterobacteria. Thus, the feeding of infant formula with a predominance of whey protein leads to the formation of "suboptimal intestinal flora".

Because infants in the first weeks of life have underdeveloped immune system and immature intestine, development of suboptimal intestinal flora can lead to infection, diarrhea, allergic reactions and inflammation. Mainly infants aged from 0 to 30 days, receiving a mixture containing mainly whey protein of cow's milk subjected to these risks, because their fecal flora is most different from that of infants who are breastfed.

The objective of this is about of the invention is to create a nutritional or pharmaceutical composition, which reduces the risks associated with the use of baby food, in which the predominant whey.

This problem is solved by a composition according to claim 1 of the claims.

The composition according to the invention is characterized by the fact that the weight ratio of casein to whey is from 1:1 to 1:2.4 and that this composition contains:

a) at least 3 grams of arginine per 100 g protein;

b) at least 10 wt.% linoleic acid (LA) of the total fatty acids;

C) at least 1 wt.% alpha linoleic acid (ALA) of the total fatty acids;

g) at least one long-chain polyunsaturated fatty acid (LCPUFA) in an amount exceeding 0.1 wt.%, of the total fatty acids, with the specified long-chain polyunsaturated fatty acid (LCPUFA) selected from the group consisting of docosahexaenoic acid (DHA), arachidonic acid (ARA) and eicosapentaenoic acid (EPA);

d) 5-25 wt.% at least one polyunsaturated fatty acid of the total fatty acids; and

e) 2-12 g unassimilated oligosaccharides having a degree of polymerization of from 2 to 100, per 100 g dry weight of the composition.

This composition stimulates the maturation of the immune system and the development of the intestine. The composition according to the invention is particularly suitable for the prevention and/or treatment in infants inflammatory is of deseases, such as infection, diarrhea, and allergies. This composition:

- stimulates the development of "optimal intestinal flora" (i.e. flora, like the flora derived breastfeeding);

- stimulates the development of the gastrointestinal tract, thus preventing the admission of such allergens as bacteria, toxins and food allergens in the General circulation;

- stimulates the maturation of the immune system, resulting in better protection if the allergen, pathogen or toxin will penetrate through the intestinal barrier and/or fall in the General circulation;

and at the same time provides optimal nutrition to the baby.

It is believed that the physiological processes underlying the development of intestinal flora low risk of developing bowel and maturation of the immune system are closely interrelated and interdependent. Thus, infant formula must contain all those ingredients in the appropriate ratio, which stimulate the development of the intestine, the maturation of the immune system and the development of intestinal flora low risk. The optimal combination of ingredients baby better protected from allergens. The present composition provides an optimal combination of ingredients. Due to the fact that the ingredients often act on different mechanisms, the ingredients of the composition described which act synergistically, providing the baby increased resistance and reduced incidence of inflammatory diseases, in particular allergies.

The described composition contains oligosaccharides with a low degree of polymerization. These oligosaccharides stimulate the formation of intestinal flora with low risk, in particular to reduce the number of potentially pathological intestinal bacteria, such as Clostridium, enterobacteria and/or enterococci, and stimulate the colonization of bifidobacteria and lactobacilli. Bifidobacteria and lactobacilli stimulate the development of the intestine, for example, by stimulating the synthesis of focalisation epithelial cells of the intestine. The best stimulation is achieved by introducing a mixture of oligosaccharides, in particular mixtures of oligosaccharides, including neutral and acidic oligosaccharides. These oligosaccharides also have a direct effect on the immune system by reducing Th2 response and increased Th1 response. It was found that the described composition, which includes oligosaccharides can be used to restore the disturbed balance of responses (Th1/Th2 and for treatment of diseases that are associated with the presence of the imbalance of Th1/Th2, such as autoimmune reaction and allergic reaction.

However, even when the combination of oligosaccharides from whey protein and, originating from a source other than a person, infants receiving such a composition is exposed to increased risks of infectious diseases during the first month of life. Thus, it is desirable to further improve the development of the immune system and/or intestines.

Surprisingly it was found that LCPUFA actually reduce epithelial translational permeability. In contrast to what was reported Usami et al (Clinical Nutrition 2001, 20(4): 351-359), it was found that C18 and C20 polyunsaturated fatty acids, in particular eicosapentaenoic acid (EPA; C20:5 n3), docosahexaenoic acid (DHA; C22:56 n3) and arachidonic acid (AA; C20:4), can effectively reduce the permeability of tight intercellular connections of the intestinal epithelium, thus, stimulate the development of the intestine. Thus, the described composition successfully contain LCPUFA. In addition, essential fatty acids linolenic acid (C18:2 n6) and alpha-linolenic acid (C18:3 n3) necessary for the development of the immune system, and for the development of the intestine. In another highly preferred embodiment, the described composition also contains gamma-linolenic acid (GLA; C18:3 (n-6)). Consequently, the described composition contains linoleic acid and alpha-linolenic acid.

Optional, but highly preferred compositions described the Oia also contains nucleotides and/or nucleosides. Nucleotides stimulate the development of the intestine, reduce the number of cases of diarrhea and stimulate the immune system. Infants receiving the mixture, supplemented with nucleotides, compared with infants receiving the mixture without nucleotides, have increased titers of antibodies after exposure to the antigen and antigen stimulation activity of killer cells. (Carver et al Acta Paediatrica, (1999) Vol. 88, No. Sup 430, p. 83-88).

The composition according to the invention contains whey proteins originating from a source, not a man, long-chain polyunsaturated fatty acids and oligosaccharides.

As mentioned above, the present invention provides a composition comprising whey and casein) in a weight ratio of casein to whey from 1:1 to 1:2.4 and at least 3 grams of arginine per 100 g protein.

The range of the ratio of casein/whey from 1:1 to 1:2,4 covers all values lying within this range, and therefore, the following values of the ratio of casein to whey: 1:1, 1:1,1, 1:1,2, 1:1,3, 1:1,4, 1:1,5, 1:1,6, 1:1,7, 1:1,7, 1:1,9, 1:1,2, 1:1,3, 1:1,4, 1:1,5, 1:1,6, 1:1,7, 1:1,8, 1:1,9, 1:2,0, 1:2,1, 1:2,2, 1:2,3, and 1:2.4 in the preferred embodiment, the ratio of casein:whey is 1:1,4-1,6, even more preferably about 1:1,5 (40:60).

Preferably arginine is present in an amount of from 3 to 8 g of arginine per 100 g protein component. This range reveals the armed forces the values and in particular all integer values lying in this range, for example 3, 4, 5, 6, 7 and 8, In this composition preferably contains 4-5 grams of arginine per 100 g protein.

Presented in LCPUFA composition selected from the group comprising DHA, AA and EPA. This means that the composition may include one or two or three of these long-chain polyunsaturated fatty acids.

The range from 5 to 25 wt.%, set for polyunsaturated fatty acids, covers all values that fall in this range.

This composition does not include a composition having the composition of the women's breast milk. This method does not include the method of applying the composition, with the composition of the women's breast milk. Thus, preferably the described method includes the use of a composition, having in its composition a substance originating from a source, not a person, preferably fibrous carbohydrates, fat and/or protein from a source, not a person, preferably a plant, animal, microbial or synthetic origin. Preferably all parts and components included in the compositions according to the invention, obtained from sources not related to the human race.

The macronutrients

The described composition can be successfully used as baby food. So what I infant formula preferably contains a fatty component, the protein component and a carbohydrate component and preferably is introduced into the baby's body in liquid form.

The preferred implementation of the present invention relates to compositions and in particular to child nutrition, containing 30 to 60 en% lipid, 5-15 en% protein and 25-75 en% carbohydrates. Preferably the composition comprises 5-15 en% protein, 30 to 60 en% fat and 25-65 en% carbohydrates. More preferably, the present composition contains 43-53 en% lipid, 7-11 en% protein and 43-53 en% carbohydrates (en% is short for energy percentage and shows the contribution of each component to the total caloric content of the composition).

The protein component described baby food contains casein and whey in a specified weight ratio. Casein and/or whey preferably obtained from the milk of a mammal, not related to the human race. For optimal infant feeding in this composition contains arginine in normalized quantity. The term "protein" or a protein component in this context means the total protein, polypeptides, peptides and amino acids. Arginine is an essential in the present compositions. It reduces the prevalence of inflammatory conditions of the intestine (Amin et al the Journal of Pediatrics, (2002) Vol. 140, No. 4, p. 425-431). Moreover, arginine stimulates the immune system and is required for maintaining healthy immunodeficiency, the Noah system (Niever et al, Biomedicine &Pharmacotherapy, (2002) Vol. 56, No. 10, p. 471-482). And casein, and whey contain arginine, but in most dairy sources (e.g., whey and casein of cow's milk), casein and whey provide insufficient amounts of arginine. Preferably at least part of the arginine added to the composition in the form of free amino acids, for example, L-arginine, or in the form of its salt or ester, with the free amino acid is preferred. In the described composition preferably contains between 75 and 500 mg of arginine in the form of free amino acids per 100 g of dry baby food, and more preferably between 150 and 400 mg of arginine in the form of free amino acids per 100 g of dry baby food.

Carbohydrates in the described compositions are preferably provided in more lactose, i.e. preferably at least 75 wt.% total digestible carbohydrates provided with lactose, preferably at least 90 wt.%.

Protein with low content of threonine

Infant formula with a predominance of whey obtained from a protein source, not related to the human race, compared with breast milk usually has a high content of bioavailable threonine. Human milk contains a relatively small amount of bioavailable threonine. Thus, in the prior art those provided the ideological techniques to reduce the content of threonine in mixtures with a predominance of whey (for example, see EP 1048226, WO 01/11990 and EP 741522). Use baby food with a predominance of whey with a reduced content of threonine provides in vivo contents of threonine, comparable to those in infants who are breastfed. The described composition is preferably a composition with a low content of threonine, i.e. a composition which contains 2-6 grams threonine per 100 g protein. Low levels of threonine, for example, can be achieved through the use of products from milk whey obtained by ultrafiltration or some sour whey products.

The content of essential fatty acids

The described composition contains at least 10 wt.% linoleic acid (LA) of the total fatty acids, preferably between 11 and 20 wt.%, more preferably between 12 and 15 wt.%. The described composition contains at least 1 wt.% alpha linoleic acid (ALA) of the total fatty acids, preferably between 1.5 and 4 wt.% ALA, even more preferably between 2 and 2.5 wt.%. To reduce the load on the intestines weight ratio LA/ALA preferably between 2 and 10, preferably between 5 and 7.5.

The described composition preferably contains between 0.05 and 5 wt.% gamma-linolenic acid (GLA) from the total content of fatty acids, predpochtitelnei 0.1 and 1 wt.%.

The content of long-chain polyunsaturated fatty acids

The described composition contains at least one long-chain polyunsaturated fatty acids with 20 or 22 carbon atoms (LCPUFA) in an amount exceeding 0.1 wt.%, of the total content of fatty acids selected from the group consisting of docosahexaenoic acid (DHA), arachidonic acid (AA) and eicosapentaenoic acid (EPA). Preferably the composition comprises DHA in an amount exceeding 0.1 wt.%, of the total content of fatty acids and AA in excess of 0.1 wt.%, of the total content of fatty acids.

Preferably at least one LCPUFA from this group is included in the composition in an amount of between 0.15 and 1 wt.% of the total content of fatty acids. Preferably at least two of these LCPUFA, present in an amount between 0.15 and 1 wt.% of the total content of fatty acids in the composition. Preferably the composition contains AA and DHA, even more preferably AA, DHA and EPA.

The AA content preferably does not exceed 5 wt.%, more preferably does not exceed 1 wt.%, more preferably between 0.1 and 0.6 wt.% of the total content of fatty acids. In the described composition has been successfully added EPA and/or DHA to balance the actions of AA, for example, reducing the potential Pro-inflammatory actions which I metabolites of AA. The excess of AA metabolites can cause inflammation. Thus, in this composition preferably contains AA, EPA and/or DHA, where the weight ratio of AA/DHA is preferably above the 0.25, preferably above 0.5, more preferably above 1. The ratio of AA/DHA, preferably less than 25, preferably less than 10. The weight ratio of AA/EPA preferably between 1 and 100, more preferably between 5 and 20. The weight ratio of EPA/DHA preferably 1 or below, more preferably below 0.5.

In a preferred embodiment, the LCPUFA content does not exceed 3 wt.% of the total fatty acids, because it is necessary to simulate breast milk as closely as possible. For this reason, the described composition preferably contains less than 1 g of omega-3 LCPUFA per 100 g fatty acids, more preferably between 0.1 and 0.75 g per 100 g fatty acids. The content of omega-6 LCPUFA preferably does not exceed 2 g per 100 g fatty acids, and is preferably between 0.1 and 0.75 g per 100 g fatty acids.

Data LCPUFA and other fatty acids may be provided in the form of free fatty acids, triglycerides, phospholipids or as a mixture of one or more of the above forms. The described composition successfully contains at least one of the acids AA and DHA in phospholipid form, as it reduces the spread of TradeNet inflammatory bowel disease. The described composition preferably contains between 0.1 and 5 mg AA from phospholipid per gram total fat, and between 0.1 and 5 mg of DHA from phospholipid per gram total fat. Preferably AA and/or DHA at least partially in the form of phosphatidylcholine (PC) and/or phosphatidylethanolamine (PV), for example, AA and/or DHA-containing FE and/or PF.

Monounsaturated fatty acid

The described nutrient mixture to ensure adequate nutrition preferably also contains omega-9 (n-9) fatty acid, preferably oleic acid, 18:1). Preferably the present composition provides at least 15 wt.% n-9 fatty acids of the total fatty acids, more preferably at least 25 wt.%. The content of n-9 fatty acids is preferably less than 80 wt.% of the total content of fatty acids. To ensure adequate nutrition in the described compositions preferably the weight ratio of saturated fatty acid/fatty acid between 2 and 5. Preferably the weight ratio of monounsaturated fatty acid/saturated fatty acid between 0.5 and 2.

The described composition preferably contains between 5 and 25 wt.% polyunsaturated fatty acids of the total fatty acids, preferably between 10 and 20 wt.%.

The described composition further m which can be improved by incorporating stearidonic acid (C18:4n3). This composition preferably contains between 0.05 and 2 wt.% stearidonic acid of the total fatty acids, even more preferably between 0.1 and 1 wt.%.

Oligosaccharides

The described composition contains 2-12 g unassimilated oligosaccharides with degree of polymerization (DP) 2 and 100 per 100 g dry weight of the composition, preferably between 3 and 8 lags, more preferably between 5 and 7.5 GMS. After conversion of the powder into the liquid and the introduction of an infant, a liquid mixture of these quantities are not assimilated oligosaccharides provide desirable effects without causing intestinal discomfort. Suitable unassimilated oligosaccharides are not digested or only partially digested in the intestine under the influence of acids or digestive enzymes, represented in the upper gastrointestinal tract of man (small intestine and stomach), but not subject to fermentation by intestinal flora of man. These oligosaccharides, preferably water-soluble (solubility greater than 1 g of oligosaccharide 1 liter of water). The average DP of this oligosaccharide is preferably less than 40, even more preferably 20. Optimally, the described composition contains between 2 and 12 g of oligosaccharides with a value of DP 2-60, preferably with a value of 2-10 DP (i.e. the sum of the masses of those nucleotides with a value of DP 2, 3, 4, 5, 6, 7, 8, and 10).

In accordance with another embodiment, at least one oligosaccharide, which is part of the described compositions selected from the group consisting of inulin, fructo-oligosaccharides, not digested dextrins, galactooligosaccharides (including transplantationfollow), xylooligosaccharides, arabinopyranoside, glucooligosaccharides of mannooligosaccharides, lacto-N-neoteroi, focalisation (containing at least one fukanou sharenow unit), acidic oligosaccharides (see below, for example, the uronic acid oligosaccharides, such as pectin hydrolysate and mixtures thereof.

Preferably, the described composition contains at least one component selected from the group consisting of inuline and fructo-oligosaccharides, and at least one component selected from the group consisting of galactooligosaccharides (including transplantationfollow) and pectin hydrolysate. In a very preferred embodiment, the present composition contains 2 to 12 g of oligosaccharides with a DP of 2 to 10 and β-linked sugars galactose and glucose, more preferably transplantological (i.e. [gal]n-glu, where n is from 2 to 10). In a particularly preferred embodiment, the described composition contains transplantological (i.e. [gal]n-glu, where n RA is but from 2 to 10), pectin hydrolysate and at least one component selected from the group consisting of fructo-oligosaccharides and inulin. The proposed oligosaccharide can also be an oligosaccharide derived from animal milk, a mixture of oligosaccharides derived from animal milk, or fokusirovannyi oligosaccharide (oligosaccharide containing at least one unit fukanaga of saccharide).

To further improve the development of ulcers on the entire stretch of the intestine, in the described composition is preferably 10 wt.% oligosaccharides have a DP of 2 to 5 (i.e. 2, 3, 4 and/or 5), and at least 5 wt.% have a DP of 10 to 100. Preferably at least 50 wt.%, more preferably at least 75 wt.% oligosaccharides have a DP of 2 to 10 (i.e. 2, 3, 4, 5, 6, 7, 8, 9 and/or 10), because it is believed that they work throughout the ileum and proximal and middle part of the colon, and because it reduces the weight percent of the oligosaccharides, it is necessary to incorporate in the composition to achieve the desired effect.

The preferred weight ratio:

(oligosaccharides with DP 2-5):(oligosaccharides with DP 6-9); and

(oligosaccharides with DP 10 to 100):(oligosaccharides with DP 6-9).

Both greater than 1.

Preferably both the weight ratio is greater than 2, even more preferably greater than 5.

The described composition predpochtite the flax contains 0.5-10 g galactooligosaccharides with a DP between 2 and 10 per 100 g dry weight of the composition, more preferably from 1 to 5, the Preferred galactooligosaccharide is transplantological, as it corresponds to the breast milk oligosaccharides. The present invention preferably comprises 0.5 to 10 g fructooligosaccharide with a DP between 10 and 60 per 100 g dry weight of the composition, more preferably between 1 and 5 lags. The term "fructooligosaccharide" refers to the carbohydrate polysaccharide containing at least 10 β-linked fructose units.

Acidic oligosaccharides

To further improve the integrity of the barrier of the present composition contains acid oligosaccharides with a DP between 2 and 100, preferably from 2 to 60. The term sour or acidic oligosaccharides refers to oligosaccharides, which contain at least one acid group selected from the group consisting of N-acetylneuraminic acid, N-glycolylneuraminic acid, free or esterified carboxylic acid, sulfuric acid group and phosphoric acid group. Acidic oligosaccharide preferably contains units of uronic acid (namely the uronic acid polymer), more preferably units of the galacturonic acid. The present composition preferably contains between 0.1 and 10 GMS of acidic oligosaccharides per 100 g dry weight of the present composition, more preferably between 1 and 6 GMS 100 the dry weight.

Structure I: Polymeric acidic oligosaccharide

where R is preferably selected from the group consisting of hydrogen, hydroxy or acid groups, preferably hydroxy; and

at least one of the radicals of the group consisting of R2, R3, R4 and R5 represents N-acetylneuraminic acid, N-glycolylneuraminic acid, free or esterified carboxylic acid, sulfuric acid group and phosphoric acid group, and the remaining R2, R3, R4 and R5 are hydroxy and/or hydrogen. Preferably one of the radicals of the group consisting of R2, R3, R4 and R5 represents N-acetylneuraminic acid, N-glycolylneuraminic acid, free or esterified carboxylic acid, sulfuric acid group or phosphoric acid group, and the remaining radicals are hydroxy or hydrogen. Even more preferably one of the radicals of the group consisting of R2, R3, R4 and R5 represents a free or esterified carboxylic group, and the remaining R2, R3, R4 and R5 are hydroxy and/or hydrogen; and

n is an integer and refers to the number of exonic units (also see below the Degree of polymerization), which can be any hexose unit. Accordingly, n is an integer number between 1-5000. Preferably hexana unit (unit) is a unit of uronic acid.

The most is her preferred R1, R2 and R3 represent hydroxy, R4 is hydrogen, R5 represents a carboxylic acid, n is any number between 1 and 250, preferably between 1 and 10, and hexose unit is galacturonic acid.

Detection, measurement and analysis of preferred acidic oligosaccharides used in the method according to the invention described in applicants previously issued patent applications related to the acidic oligosaccharides, i.e. international patent publication WO 00/160378.

Preferably the acidic oligosaccharide has one, preferably two end units of uronic acid, which can be free or esterified. Preferred end unit of a uronic acid selected from the group consisting of a galacturonic acid, glucuronic acid, guluronic acid, iduronovoy acid, mannurone acid, Rybarikova acid and ultranova acid. These units can be free or esterified. In an even more preferred embodiment, end hexana unit has a double bond, which preferably is located between the positions C4 and C5 terminal hexose units. Preferably one of the terminal hexonic units contains a double bond. Terminal hexose (e.g., uronic acid) preferably has a structure corresponding with etousa structure II.

Structure II: Preferred terminal hexana acid group

where R is preferably selected from the group consisting of hydrogen, hydroxy or acid groups, preferably hydroxy (see above); and

at least one component from the group consisting of R2, R3, R4 and R5 represents N-acetylneuraminic acid, N-glycolylneuraminic acid, free or esterified carboxylic acid, sulfuric acid group and phosphoric acid group, and the remaining R2, R3, R4 and R5 are hydroxy and/or hydrogen. Preferably one of the radicals of the group consisting of R2, R3, R4 and R5 represents N-acetylneuraminic acid, N-glycolylneuraminic acid, free or esterified carboxylic acid, sulfuric acid group and phosphoric acid group, and the remaining R2, R3, R4 and R5 are hydroxy and/or hydrogen. Even more preferably one of the radicals of the group consisting of R2, R3, R4 and R5 represents a free or esterified carboxylic acid, and the remaining R2, R3, R4 and R5 are hydroxy and/or hydrogen; and n is an integer and represents the number hexonic units (also see below the Degree of polymerization), which can be any hexose unit. Accordingly, n is an integer between 1-5000, meaning the number hexonic units, and these hexose units which are preferably units of uronic acid, even more preferred are units of the galacturonic acid. The group of carboxylic acids in these units can be free or partially esterified and preferably at least partially methylated.

Most preferably, R2 and R3 represent hydroxy, R4 is hydrogen, and R5 represents a free or esterified carboxylic acid.

Acidic oligosaccharides used in the present invention, preferably derived from pectin, pectate, alginate, chondroitin, hyaluronic acid, heparin, heparan, bacterial carbohydrates, sialogogues, fucoidan, focalisation or carrageenan, more preferably from pectin and/or alginate. Preferably use pectin hydrolysate.

Nucleotides

The present composition preferably contains between 5 and 100 mg of nucleosides and/or between 5 and 100 mg nucleotides per 100 g of dry weight of the composition, more preferably between 5 and 50 mg of Nucleotides and/or nucleosides additionally stimulate the immune system, acting synergistically with the other ingredients described composition.

Zinc

Zinc is a micronutrient that is essential for growth and development of immune function. Zinc deficiency impairs overall immune function and resistance to infection. Therefore, description is by composition successfully contains zinc, preferably in the amount of 2-100 mg zinc per 100 g dry weight of the present composition, even more preferably at least 4-25 mg zinc per 100 g dry weight of the present composition. Mass of zinc calculated as elemental zinc.

A liquid composition

The described composition is preferably in powder or liquid form or pill form, where this tablet has a mass of between 5 and 25 GMS. Preferably, the described composition is provided in powdered form, as it increases the shelf life. The described composition is preferably used in oral liquid form. Before applying the described composition, it is preferably mixed with a liquid, preferably with water. In the liquid composition is preferably applied until it has a temperature of 35-40°C (preferably about 37°C), the liquid composition is preferably prepared as follows:

Method a: mix water with temperature below 30°C and a composition in accordance with any of paragraphs 1-10, with the weight ratio of water:composition of 1-10:1; and heat the mixture obtained in step a)to a temperature of between 35 and 50°C; or

Method b: mix water with temperature below 60°C and a composition in accordance with any of paragraphs 1-10, with the weight ratio of water:composition of 1-10:1; and cooling the mixture obtained in step a), until the temperature between 35 and 40 °C. Method a) is more suitable for obtaining a liquid mixture of powder, while method b) is more suitable for obtaining a liquid mixture of pills.

The irregularity of the chair (for example, a hard chair, insufficient stool, diarrhea) is a major problem for many babies and sick people who receive liquid food.

It was found that stool can be reduced through the use of the described compositions in liquid form, having an osmolarity of between 50 and 500 mOsm/kg, more preferably between 100 and 400 mOsm/kg, most preferably between 220 and 300 mOsm/kg

In connection with the foregoing problem of diarrhea, it is also important that the liquid food has no excess density of calories, because it is the cause pronounced intestinal stress. However, this mixture is necessary to ensure enough calories to feed the baby. Thus, the liquid food preferably has a density of calories between 0.5 and 0.9 kcal/ml, preferably between 0.6 and 0.8 kcal/ml

Application

The described composition has been successfully used in infants aged 0 to 2 years. The described composition has also been used successfully in the method of providing the required nutrients in premature infants (babies born before 37 weeks of pregnancy). In a preferred embodiment, done by what means the present invention relates to a method for feeding infants from 0 up to 30 days.

The described composition can be used successfully for the treatment or prevention of diseases which cause the development of the disease is the underdevelopment of the immune system and/or the intestinal barrier. The described composition can thus be used to treat or prevent diarrhea, or allergic reactions, particularly in infants aged 0 to 2 years. The described composition is in particular suitable for the treatment and/or prevention of allergic rhinitis, allergic conjunctivitis, allergic dermatitis, atopic dermatitis and/or food allergies.

The described composition is preferably provided in the form of packaged powder or pre-packaged ready-to-use mixture. To prevent damage to the product, package size ready-to-use mixture preferably does not exceed the amount of single use, for example, preferably not more than 500 ml; and packing size of the described compositions in powder form preferably does not exceed 250 receptions. Suitable packing size for the powder form is 2000 g or less, preferably 1000 g or less.

Packaged product is equipped with a label on which the consumer clearly and unambiguously explained the use of the specified product in accordance with one or more above or below the assignments, covered by the present invention. Such labels may include, for example, words such as "encourages the development of bowel and/or immune systems, reduces allergic reactions", "reduces stress", "resistance" or "reduced sensitivity" or similar words.

Thus, the essence of the present invention is the use of a composition as described herein, for the production of obtaining nutrient mixture or the medicinal product for use in a mammal for the treatment and/or prevention of inflammatory diseases, diarrhea, eczema and/or atopic dermatitis.

In addition, the essence of this invention is the use of the compositions described herein for the production of obtaining drugs for use in the method of treatment and/or prevention of inflammatory diseases, diarrhea, eczema and/or atopic dermatitis, the method involves the application of a specified composition interline or oral in mammals and in particular in infants. In a preferred embodiment, the present method relates to a method of treatment and/or prevention of infections, and this method includes the use of the described compositions.

The invention is additionally illustrated by the following examples:

Example 1: Baby food

Liquid baby food, obtained by mixing of 13.9 g of the powder with water to obtain 100 ml of the finished product, 100 ml of the specified liquid product contains:

Energy 66 kcal.

Protein - 8 en%.

1.3 g (including 0.6 g of casein; 0.8 g serum; 0,072 g of L-arginine)

Digestible carbohydrates: 44 en%

of 7.4 g (including 7,3 g lactose)

Fat - 48 en%.

3.5 g (including 0,41 g linoleic acid, 0.08 g of α-linoleic acid; 0,012 g arachidonic acid; 0.002 g eicosapentaenoic acid; 0,006 g docosahexaenoic acid; 1.4 g of oleic acid)

Fiber: 0.8 g (including 0.05 g fructooligosaccharide (Raftiline HP™, Orafti, Tienen, Belgium); 0.55 g transplantationfollow (Vivinal-GOS™ (Borculo Domo Ingredients, Netherlands); 0.20 g of pectin hydrolysate, obtained as described in EP 1373543, example 1.

Nucleotides: 0,89 mg Citizen-5-monophosphate;

0.55 mg of Uridine-5-monophosphate;

0,82 mg Adenosine-5-monophosphate;

0,20 mg Guanosin-5-monophosphate;

0,34 mg Inosine-5-monophosphate.

Osmolarity: 300 mosmol/l

In the composition additionally contains choline (6 mg/100 ml) and taurine (6,3 mg/100 ml); the minerals and trace minerals (including zinc 2 mg/100 ml) and vitamins in amounts corresponding to international standards for infant formula.

Example 2:

Packed infant formula in accordance with example 1, where the package is equipped with ethics is rigid with the indication of the application of this mixture is suitable for the prevention or treatment of allergic reactions.

Example 3:

Experimental model

The effect of diet, which includes acidic oligosaccharides, optionally in combination with a neutral oligosaccharides tested for hypersensitivity reactions of the delayed type (GCST), which is a parameter of the Th1 immune response and is determined by measuring the increase of ear swelling after local antigenic stimulation.

Used acidic oligosaccharides (AcOl), with a mean of DP between 2 and 10, obtained by the method described in international publication WO 02/42484 (see example 1). Researched diets containing 1 wt.%, 2.5 wt.%, 5 wt.% and 10 wt.% AcOl of the total weight of the diet. Used a mixture of neutral oligosaccharides (GF)containing galactooligosaccharide (GOS) (Vivinal-GOS™ (Borculo Domo Ingredients, Netherlands) and fructo-oligosaccharides (FOS) (Raftiline HP™, Orafti, Tienen, Belgium), in a weight ratio of GOS:FOS equal to 9:1. Studied the diets containing 1, 2.5 and 5 wt.% GF of the total weight of the diet. The impact of the combination of acidic and neutral oligosaccharides (GF and AcOl) was studied using a diet containing 1 wt.% GF and 1 wt.% AcOl of the total weight of the diet.

All parameters are presented as percent of control values, that is, the relative values in the group receiving the diet supplemented on what hosahalli, compared with the group receiving the control diet (without oligosaccharides).

Animals and diets

Female mice C57BI/6 at the age of 6 weeks (Harlan Nederland BV, Horst, the Netherlands) placed by the group in the normal 12-hour light-dark regime. Group size was 10 animals in the group and 3 animals in the negative control group. Animals received a semisynthetic diets (Research Diet Services, Wijk bij Duurstede, the Netherlands). Control diets were manufactured in accordance with the AIN93G specifications (Reeves et al (1993) Development and Testing of the AIN93 purified diets for rodents: results on growth kidney calcification and bone mineralisation in rats and mice. J Nutrition 123(11): 1923-31), diets with the addition of oligosaccharides based on these specifications. The carbohydrate content in the supplemented diets was kept constant by replacing the total carbohydrate oligosaccharides in terms of weight. Individual carbohydrate components were replaced, corresponding to their normal ratio in the diet. Carbohydrates in a normal diet consist of starch (40% of the total weight), corn starch (13,2%), sucrose (10%) and cellulose (5%).

The vaccination scheme

Vaccination was started after a period of two to four weeks after adaptation to new dwellings and diets. At day 0 were collected blood samples prior to vaccination. Day 1 performed the first vaccination, subcutaneously. Three weeks later collected blood samples (day 21) and others who took the booster vaccination (day 22). Nine days after the booster injection (day 31) measured the thickness of the base of the ear, using a micrometer to measure the external dimensions Digimatic (Mitutoyo, Veenendaal, the Netherlands), and the reaction of hypersensitivity of the delayed type (GCST) induced by injections in the ear mouse solution of antigen (intradermally). 24 hours after this point (day 32) was determined by reaction GCST, took a blood sample and mice were killed. The spleen was isolated and prepared for re-stimulationex-vivo.

The vaccine consisted of 100 µl of p/(subcutaneous) injection of a mixture of 1:1 solution of antigen and adjuvant Stimune (Specol, Cedi-diagnostics BV, Lelystad, the Netherlands). The antigen solution was a dilution of 1:100 vaccines Influvac 2002/2003 (Solvay Pharmaceuticals, Weesp, the Netherlands) in PBS. Influvac is trivalent protein vaccine containing h µg/ml hemagglutinin three different strains of influenza.

To determine the reactions GCST mice in both ears was subcutaneously injected as an incentive GCST 25 ál detalizirovannoi vaccines Influvac.

Cell culture

Splenocytes were isolated from spleens using a fine-meshed sieve (Becton Dickinson, Erembodegem, Belgium). Erythrocytes were literally by incubating for 5 minutes on ice. After washing the culture medium not containing phenol red were counted cells (Coulter Counter, Beckman Coulter, the Netherlands) and kept the same applies to the its. To stimulate the culture was treated with 0.1 ág/ml detalizirovannoi vaccine, Influvac. Cells were planted in 96-well plates in a dilution of 1·106cells per well. The culture medium consisted of RPMI-1640 with HEPES buffer and 2 mm L-glutamine (Invitrogen, Merelbeke, Belgium) with 10% fetal calf serum (FCS). Cultures were incubated for 5 days at 37°C and 5% CO2. Then, the collected supernatant was frozen at -80°C until analysis. Cell proliferation was measured in parallel cultures to enable3H-thymidine was added to cultures in the last 18 hours at a concentration of 0.4 µci/well. After 5 days, using a Filtermate harvester (Perkin Elmer, Zaventem, Belgium), cells were collected and counted by the counter cell Micro-Beta (Perkin Elmer, Zaventem, Belgium). Radioactive decay was measured for 1 minute per well, and the number of pulses per minute (cpm) were recorded as a measure of the rate of cell proliferation.

The cytokines investigated in the supernatant fluids cultures stimulated Influvac. IL-2, IL-5, IL-10 and IFN-gamma were investigated on the system Bio-Plex using special mixed granules for these cytokines (Bio-Rad, Veenendaal, the Netherlands). The cytokines investigated in accordance with the instructions of the manufacturer. IL-4 was measured by ELISA using a set Pharmingen OptEIA mouse IL-4 (Becton Dickinson, Erembodegem, Belgium), in accordance with the instructions of company-producers of the El.

Results

The reaction GCST on acidic oligosaccharides

Rations containing AcOl in the dosage of 1 wt.%, 2.5 wt.% and 5 wt.%, induced a statistically significant increase in reaction GCST, demonstrating dose-dependent increase (see Table 1). The observed effect describes the successful application of acidic oligosaccharides in the method according to the invention.

Table 1
Wt.% acidic oligosaccharides in the dietThe reaction GCST (%)
0 (control)100
1122
2,5136*
5140*
* means significant difference (P<0,05) with the control

The reaction GCST at acidic and neutral oligosaccharides

The combination of 1 wt.% GF, 2.5 wt.% GF and a mixture of 1 wt.% GF 1 wt.% AcOl causes a statistically significant increase in reaction GCST (see Table 2). The observed effect describes the successful application of unassimilated oligosaccharides, in particular the combination of acidic and neutral oligosaccharides, in the method according to the invention.

Table 2
Wt.% acidic oligosaccharides in the dietThe reaction GCST (%)
0 (control)100
1 wt.% GF132*
1 wt.% AcOl122
2.5 wt.% GF129*
2.5 wt.% AcOl136*
1 wt.% GF and 1 wt.% AcOl159*
* means significant difference (P<0,05) with the control

Influvac-specific proliferation of acidic oligosaccharides

The use of diets containing 2.5 wt.% and 5 wt.% acidic oligosaccharides (AcOl), induces a significant reduction steps on Influvac-specific proliferationex vivo(see Table 3). The observed effect describes the successful application of acidic oligosaccharides in the method according to the invention.

Influvac-specific proliferation of a mixture of acidic and neutral oligosaccharides

Applying a combination of 1 wt.% GF and 1 wt.% AcOl induces a significant reduction of the effects on antigen-specific proliferation (see Table 3). Since e is the effect on the reaction GCST significantly improved with the use of rations, containing only acidic or neutral oligosaccharides, these results characterize the synergistic effect provided by the use of acidic and neutral oligosaccharides. The observed effect characterizes the successful combination of acidic and neutral oligosaccharides in the method according to the invention. Reduced proliferation is a characteristic to reduce Th2 response, balancing the action of Th1/Th2, when using this method.

Table 3
Wt.% oligosaccharides in the dietInfluvac-specific proliferation (%)
0 (control)100
1 wt.% GF100
1 wt.% AcOl92
2.5 wt.% AcOl61*
5 wt.% AcOl54*
1 wt.% GF and 1 wt.% AcOl50*
* means significant difference (P<0,05) with the control

Th1/Th2 balance: cytokine profiles after application of the acidic oligosaccharides

takinoue profiles were measured in the supernatant fluids of cultural influvac-specific splenocytes. The results are presented in percentage in comparison with the values vaccinated control group (i.e. not receiving oligosaccharides). Compared with the control, the use of diets containing 2.5 wt.% and 5 wt.% AcOl, led to a decrease in Th2-associated cytokines IL-4, IL-5 and IL-10, whereas Th1-associated cytokine IL-2 was increased, and IFN-γ was not significantly reduced (see Table 4). These results are characteristic of Th1/Th2 balancing action of acidic oligosaccharides and characteristic for the successful application of acidic oligosaccharides in the method according to the invention, for example, in the treatment and/or prophylaxis of diseases which are characterized by relatively low Th1 immunity.

Th1/Th2 balance: cytokine profiles after application of acidic and neutral oligosaccharides

Compared with the control, using a combination of 1 wt.% GT and 1 wt.% AcOl has led to increased Th2-associated cytokines IL-4, IL-5 and IL-10, whereas Th1-associated cytokines IL-2 and IFN-γ were not reduced (see Table 4, where data are presented in percentage in comparison with the values in vaccinated control group (not receiving oligosaccharides)). These results are characteristic of Th1/Th2 balancing action of the combination of acidic and neutral oligosaccharides and characterize the successful application of acidic oligosaccharides way to posovremeni, for example, in the treatment and/or prophylaxis of diseases which are characterized by relatively low Th1 immunity. In particular, the ratio of IL-4/IFN displays the balance of Th2/Th1. In other words, the reduced ratio characterizes the stimulation of Th1 and/or inhibition of Th2, and in any case describes the Th1-Th2 balance the action described oligosaccharides.

Table 4
Wt.% oligosaccharides in the dietCytokine
IFN-γ (%)IL2 (%)IL1 0 (%)IL4 (%)IL5 (%)ratio
IL4/IFN-γ
0 (control)100100100100100100
1 wt.% AcOl100196*70837285
2.5 wt.% AcOl75 11658*556675
5 wt.% AcOl69161*44*33*56*51*
1 wt.% GF and 1 wt.% AcOl9312345*44*55*45*
* means significant difference (P<0,05) with the control

1. Nutrient composition in the form of baby food containing fat component, a protein component and a carbohydrate component and including whey and casein, characterized in that the weight ratio of casein to whey is from 1:1 to 1:2,4, and the composition contains:
a) at least 3 grams of arginine per 100 g protein;
b) polyunsaturated fatty acids, including:
at least 10 wt.% linoleic acid of the total fatty acids;
at least 1 wt.% alpha-linoleic acid of the total fatty acids; and
at least one long-chain polyunsaturated fatty acid that is selected and the group, consisting of docosahexaenoic acid, arachidonic acid and eicosapentaenoic acid in an amount exceeding 0.1 wt.%, of the total content of fatty acids and the content of polyunsaturated fatty acids up to 25 wt.% of the total content of fatty acids;
(C) 2-12 g unassimilated oligosaccharides having a degree of polymerization of from 2 to 100 per 100 g of dry weight of the composition and including neutral and acidic oligosaccharides, and acidic oligosaccharides contain units of uronic acid.

2. The composition according to claim 1, characterized in that it contains transplantological, pectin hydrolysate and at least one component selected from the group consisting of fructooligosaccharide and inulin.

3. The composition according to claim 1, characterized in that it contains 2-100 mg zinc per 100 g dry weight of this composition.

4. Composition according to any one of claims 1 to 3, characterized in that the protein component is 5-15 EN.% (energy%), the fat component is 30 to 60 EN.%, and the carbohydrate component comprises 25-75 EN.%.

5. Composition according to any one of claims 1 to 3, characterized in that it further comprises between 5 and 100 mg of nucleotides and/or between 5 and 100 mg of nucleoside per 100 g dry weight of this composition.

6. Composition according to any one of claims 1 to 3, characterized in that it contains 2-6 grams threonine per 100 g protein component.

7. To the position according to any one of claims 1 to 3, characterized in that it contains docosahexaenoic acid in an amount exceeding 0.1 wt.% of the total fatty acids and arachidonic acid in an amount exceeding 0.1 wt.% of the total fatty acids, and that the weight ratio of the arachidonic acid/docosahexaenoic acid ranges from 0.25 to 25.

8. Pharmaceutical composition in the form of baby food, used in the treatment and/or prevention of inflammatory diseases, diarrhea, eczema and/or atopic dermatitis containing fat component, a protein component and a carbohydrate component and including whey and casein, characterized in that the weight ratio of casein to whey is from 1:1 to 1:2,4, and the composition contains:
a) at least 3 grams of arginine per 100 g protein;
b) polyunsaturated fatty acids, including:
at least 10 wt.% linoleic acid of the total fatty acids;
at least 1 wt.% alpha-linoleic acid of the total fatty acids; and
at least one long-chain polyunsaturated fatty acid selected from the group consisting of docosahexaenoic acid, arachidonic acid and eicosapentaenoic acid in an amount exceeding 0.1 wt.%, of the total content of fatty acids and the content of polyunsaturated fatty KIS is from up to 25 wt.% of the total content of fatty acids;
c) 2-12 g unassimilated oligosaccharides having a degree of polymerization of from 2 to 100 per 100 g of dry weight of the composition, and including neutral and acidic oligosaccharides, and acidic oligosaccharides contain units of uronic acid.

9. The composition according to claim 8, characterized in that it contains transplantological, pectin hydrolysate and at least one component selected from the group consisting of fructooligosaccharide and inulin.

10. The composition according to claim 8, characterized in that it contains 2-100 mg zinc per 100 g dry weight of this composition.

11. Composition according to any one of p-10, characterized in that the protein component is 5-15 EN.% (energy%), the fat component is 30 to 60 EN.%, and the carbohydrate component comprises 25-75 EN.%.

12. Composition according to any one of p-10, characterized in that it further comprises between 5 and 100 mg of nucleotides and/or between 5 and 100 mg of nucleoside per 100 g dry weight of this composition.

13. Composition according to any one of p-10, characterized in that it contains 2-6 grams threonine per 100 g protein component.

14. Composition according to any one of p-10, characterized in that it contains docosahexaenoic acid in an amount exceeding 0.1 wt.% of the total fatty acids and arachidonic acid in an amount exceeding 0.1 wt.% of the total fatty acids, and the fact that Vescovo is the ratio of the arachidonic acid/docosahexaenoic acid ranges from 0.25 to 25.

15. The way to prevent allergies or diarrhea in a mammal, involving the administration to a mammal of a composition according to any preceding item.

16. The method according to item 15, in which the above composition is administered interline or oral.

17. The method according to item 15 or 16, in which the specified mammal is a child.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions relates to medicine and can be applied for treatment of hyperaemia and edema of mucous membrane of upper airways. For this purpose introduced is loratadine or proper quantity in form of its acceptable salt in combination with phenylephrine or as monomedication. Loratadine is introduced in regimen 2.5 mg four times per day, and phenylephrine is introduced in regimen 8-10 mg four times per day. Loradadine introduction in regimen 2.5 mg per day makes it possible to reach high efficiency of treatment in absence of side reactions.

EFFECT: treatment efficiency by loratadine in combination with phenylephrine in claimed regimen is conditioned by their synergetic effect as well as in absence of side reactions.

28 cl, 3 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to peptides inhibiting mucin hypersecretion. The peptides have an amino acid sequence containing up to 24 amino acid residues of the sequence GAQFSKTAAKGEAAAERPGEAAVA which can have at least one amino acid substitute in said sequence selected from a group consisting of the substitute of A by K, the substitute of F, K, G, Q, S, T and/or E for A; or the substitute of Q for E.

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28 cl, 9 tbl, 5 ex

FIELD: medicine.

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3 cl, 4 tbl, 4 ex

FIELD: medicine, pharmaceutics.

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3 cl, 12 dwg, 1 tbl, 1 ex

FIELD: medicine, pharmaceutics.

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7 cl, 9 ex, 2 tbl

FIELD: chemistry.

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39 cl, 1 tbl, 99 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to application in an effective amount and to new nicotine receptor agonists described by general formula (i) or (ii) for treating inflammatory diseases chosen from a group including asthma, chronic obstructive pulmonary disease (COPD), interstitial pulmonary tissue fibrosis (IPF), sarcoidosis, hypersensitivity pneumonitis (HP), chronic hypersensitivity pneumonitis and bronchiolitis obliterans organising pneumonia (BOOP). The compounds (i) and compounds (ii) relate to formulae (i) (ii) where in formula (i) R1 and R2 independently mean alkyl with 1-10 carbon atoms; Xa means CH or N; Ya means one or more substitutes chosen from hydrogen, halogen, cyano, hydroxyl, alkyl with 1-10 carbon atoms optionally substituted with one or more halogen atoms, and alkoxy with 1-10 carbon atoms; n means an integer 0 or 2; J means a counterion representing a compound for maintaining electric neutrality, e.g., halogen, sulphate, sulphonate; in formula (ii) R3 is chosen from or Xb means N or N+-R10; R4 means one or more substitutes chosen from hydrogen, halogen; each R10, R11 and R12 independently means alkyl with 1-10 carbon atoms; provided the presence of the counterion when Xb means N+-R10.

EFFECT: use of nicotine receptor agonists in the effective amount for treating inflammatory diseases.

26 cl, 40 dwg, 3 tbl, 38 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine and concerns cat allergen fused proteins and application thereof. Substance of the invention involves a compositions containing a virus-like particle (VLP) or a viral particle and at least, one antigen, first of all at least, one cat antigen, and more specifically at least one cat antigen which is human allergen. In specific versions of the invention, said antigen represents cat antigen Fel d1 or its fragment covalently bound with the VLP.

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25 cl, 20 ex, 5 tbl, 4 dwg

FIELD: medicine.

SUBSTANCE: daily in morning hours nasal passages are washed with physiological solution, 10% oil solution of vitamin E in dose 3 drops into each passage is dropped into both nasal passages. After 2 hours transcutaneous impact with constant magnetic field and low-intensity laser irradiation with power 30-80 mW, wavelength 0.85-0.89 mcm, pulse repetition rate 50-80 Hz is carried out on region of projection of thymus, maxillary sinuses, submandibular lymph nodes, spinous process of the third cervical vertebra, mastoid process. Time of impact is 60 seconds per each region. Ozonised olive oil is dropped into each nasal passage in dose 3 drops. After that, by means of light-conducting nozzle performed is impact on anterior parts of inferior nasal conchas with pulse red irradiation with wavelength 0.63-0.65 mcm, pulse power of irradiation at outlet not less than 5 W, pulse repetition rate 50-80 Hz, frequency of light diode modulation - 4-8 Hz. Impact time is 60-120 seconds. Total treatment course is 7 days with 4 month interval, 3 times per year. During the first interval between courses bacterial immunomodulator IRS-19 is introduced in age dose in therapeutic regimen. During the second interval antihomotoxic therapy with drugs Luffel and Lymphomyosot is administered.

EFFECT: method makes it possible to increase treatment efficiency, reduce frequency of disease recurrences, reduce medication load in case of allergic rhinites, which usually require long treatment.

2 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention refers to producing versions of group I Poaceae (holy grass) allergen, also can be used either for specific immunotherapy (hyposensitisation) of patients with grass pollen allergy, or for preventive immunotherapy of grass pollen allergies. The produced versions are characterised by Cys41 Ser, Cys57Ser, Cys69Ser, Cys72Ser, Cys77Ser, Cys83Ser and Cysl39Ser substitutes in a Phi p1 mature protein sequence. Also, a structure of the allergen versions can be presented with no fragments relevant to amino acid residues 1-6, 1-30, 92-104, 115-119, 175-185 and 213-220 or 1-6, 115-119 and 213-220 as a part of a primary sequence of Phi p1 mature protein.

EFFECT: invention allows producing a version of group I Poaceae allergen characterised lower IgE responsiveness as compared with common wild allergen and substantially maintained responsiveness to T-lymphocytes.

8 cl, 9 dwg, 2 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed is application of arbidol (1-methyl-2-phenylthiomethyl-3-carb-ethoxy-4-dimethilamino-methyl-5-oxy-6-bromidole of monohydrate hydrochloride) or its pharmaceutically acceptable salts and/or hydrates for manufacturing topic medications, intended for treatment of inflammatory and allergic skin diseases and topic pharmaceutical composition on its basis.

EFFECT: demonstrated is therapeutic action - reduction of skin affection on standard models of allergic and contact dermatitis with minimal number of side effects.

5 cl, 2 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed is novel combination of active substances for creation of pharmaceutical composition, liquid water ambroxol-based medications for treatment of diseases of respiratory ways with formation of viscous sputum, which possess expectorant, mucolytic, anti-inflammatory effect. Preparation contains ambroxol, pharmaceutically suitable water-soluble salt of glycyrrizic acid and extract of thyme.

EFFECT: preparation in accordance with invention makes it possible to obtain efficient clinical results (reduction of coughing period duration and quicker recovery of patients with diseases of respiratory ways) and provides multi-directional action on cough pathogenesis in whole.

16 cl, 3 tbl, 10 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I)

, where A denotes -CH2-, -O- or -NR'-, in which R' denotes hydrogen or C1-6alkyl, or R' and R4 form C2-5alkylene; R1 denotes hydrogen, amine group, C1-6alkyl, hydroxy group, -NR'R", (C0-6alkylene)-NR'R", where R' and R" are independently selected from a group comprising hydrogen, C1-6alkyl, heteroalkyl, formyl, C1-6alkylcarbonyl, arylcarbonyl optionally substituted with halogenalkyl, C1-6alkylsulphonyl, arylsulphonyl or -(C0-6alkylene)-OR', where R' denotes hydrogen, C1-6alkyl, formyl or C1-6alkylcarbonyl; R2 , R2 and R2 independently denote hydrogen, halogen, C1-6alkyl or C1-6alkoxy group; R3 denotes hydrogen, C1-6alkyl, aryl-C1-6alkyl, aryl optionally substituted with halogen, or heteroaryl, where the heteroaryl is a monocyclic or bicyclic ring containing 5-6 ring atoms and at least one aromatic ring containing one or three ring heteroatoms selected fron N, O and S, where the remaining ring atoms are carbon atoms, and the bonding site of the heteroaryl radical must be on the aromatic ring; R4 denotes hydrogen, C1-6alkyl, aryl, C3-7cycloalkyl-C1-6alkyl, aryl-C1-6alkyl; R5 denotes hydrogen or C1-6alkyl; or R4 and R5 together with the carbon atom to which they are bonded, form an optionally substituted C3-7cycloalkyl ring; R6 denotes hydrogen or C1-6alkyl; and pharmaceutically acceptable salts thereof, where the term "aryl" denotes phenyl or naphthyl. The invention also relates to a pharmaceutical composition based on compounds of formula I and having a inhibitory activity towards chymase.

EFFECT: novel compounds which can inhibit chymase are obtained and can be used as medicinal agents.

22 cl, 79 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical composition for peroral introduction in form of food film, where food film includes diclofenac in form of free acid or diclofenac resinate in amount from 10 to 50 wt % and film-forming polymer in amount from 10 to 80 wt % per dry weight of obtained food film. Composition contains from 10 to 50 mg of diclofenac in dissolved or evenly dispersed state, food film being 20-250 mcm thick.

EFFECT: invention ensures fast decomposition of food film in patient's oral cavity for less than 20 seconds.

9 cl, 13 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted oxazole derivatives of general formula I. The disclosed compounds have affinity to the µ-opioid receptor. In general formula I

, n equals 0, 1 or 2, R1 denotes a phenyl residue bonded through a C1-C3alkyl chain, R2 denotes phenyl or thienyl, each of which is unsubstituted or mono-substituted with F or Cl, R3 and R4 independently denote a saturated, branched or straight C1-C6alkyl, phenyl or a phenyl residue bonded through a C1-C3akyl chain, or R3 and R4 together form an unsubstituted five-, six- or seven-member saturated ring which can optionally contain an extra heteroatom selected from a group comprising O or NR9, where R9 denotes phenyl or a phenyl residue bonded through a C1-C3alkyl chain, any of which is unsubstituted or mono-substituted with a substitute selected from a group comprising F, Cl, Br, I and O-C1-C6alkyl, where the ring can be optionally condensed with a phenyl ring, R5 and R6 independently denote a saturated, branched or straight C1-C6alkyl, R7 and R8 independently denote a saturated, branched or straight unsubstituted C1-C6alkyl or a phenyl residue bonded through a C1-C3alkyl chain, or R7 and R8 together form an unsubstituted or mono- or disubstituted five-, six- or seven-member saturated ring, where the substitutes are selected from a group comprising C1-C6alkyl or a phenyl residue bonded through a C1-C3alkyl chain, where the ring can optionally contain an extra heteroatom selected from a group comprising S, O and NR10, where R10 denotes a phenyl or a phenyl residue bonded through a C1-C3alkyl chain, any of which can be unsubstituted or mono-substituted with O-C1-C6alkyl. The invention also relates to methods of producing the disclosed compounds, a medicinal agent containing at least one substituted oxazole derivative of formula I, use of the compounds to prepare a medicinal agent.

EFFECT: improved properties.

13 cl, 1 tbl, 150 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to inhibiting or decreasing a level of inflammation mediator release from inflammatory cells by suppressing a mechanism associated with inflammation mediator release from inflammatory cell granules by using the versions of MANS peptide.

EFFECT: invention refers to an endocellular signal transmission mechanism which allows detecting a number of new endocellular targets for the pharmacological treatment of disorders associated with inflammation mediator secretion from inflammatory cell vesicles.

25 cl, 15 dwg, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the application of a biologically active peptide which represents the amino acid sequence SEQ ID No.1.

EFFECT: preparation of a drug for modulation of at least one of the following conditions: fatigue, liver glycogen level and blood lactic acid level.

30 tbl, 14 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention describes compounds of formula I: formula I or its pharmaceutically acceptable salt, where the radical values R3, R4, R2, X1, X2, R1 are such as presented in claim 1. Also, the invention describes a pharmaceutical composition exhibiting a Tec-family kinase inhibitor activity and based on the compounds of formula I, a method of Tec-family kinase activity inhibition, and a method of producing the compound of formula I.

EFFECT: produced and described new compounds which are effective as Tec-family (eg, Tec, Btk, Itk/Emt/Tsk, Bmx, Txk/Rlk) protein kinase inhibitors, and acceptable compositions are applicable for treatment or prevention of some diseases, disorders or conditions including but not limited, autoimmune, inflammatory, proliferative or hyperproliferative, or immunologically mediated diseases.

50 cl, 18 ex, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of general formula (I) or to their pharmaceutically acceptable salts exhibiting CCR2B antagonist activity, and to a based pharmaceutical composition. (I) where P represents phenyl optionally substituted by 1 or 2 substitutes independently selected from halogen, C1-4alkyl, cyano, trifluoromethyl, C1-4alkoxy and trifluormethylthio, and R2 has the values specified in the patent claim.

EFFECT: preparation of new compounds of general formula (I) or their pharmaceutically acceptable salts exhibiting CCR2B antagonist activity.

16 cl, 340 ex

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine, namely, surgical dentistry and maxillofacial surgery and can be used for treatment and prevention of alveolitis. Ointment for treatment and prevention of alveolitis contains lanolin-vaseline base, crystalline iodine, water solution of potassium iodide, solcoseryl dental adhesive paste, anesthesin, polysorb MP, distilled water, with the following component ratio: lanolin-vaseline ointment 40.5-42.5; crystalline iodine 0.1-0.3; water solution of potassium iodide 0.4-0.5; solcoseryl dental adhesive paste 40.5-42.5; anesthesin 3.8-5.8; polysorb MP 0.3-0.5; distilled water - the remaining part.

EFFECT: invention makes it possible to accelerate healing of bone wounds, prevent development of inflammatory complications and reduce period of recovery of patients with alveolitis.

2 ex

FIELD: agriculture.

SUBSTANCE: invention relates to livestock farming. Daily cycle of one or more mammal females is divided into phase of day time with the first light mode with a share of blue light and phase of night time with the second light mode. Animals are milked at least once during night time phase. During night time phase, at least one source of light is used for light mode, which radiates light in the range of wave length of 500 nm or more, and mainly does not radiate light in the range of wave lengths below 500 nm. Produced milk may be processed to make milk products, in particular, dry milk with high content of melatonin.

EFFECT: method makes it possible to produce milk and milk products with high content of melatonin, which may be used as biologically active additives to food or as medicinal agents.

3 dwg, 3 ex, 17 cl

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