Composition for treatment and/or prevention of allergy, asthma, infection and atopic dermatitis with children born by cesarean section (versions)

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

 

The technical field to which the invention relates

The present invention relates to methods for treating and/or preventing diseases in children born by caesarean section.

The prior art inventions

Human milk contains nevereverever oligosaccharides, which specifically stimulate the development of lactic acid bacteria, such as species belonging to the genus Bifidobacterium and Lactobacillus, and prevent the development and/or adhesion to the intestinal wall of the colon other (pathogenic) bacteria. So when the child receives breast milk, intestinal flora of the child is developing in a healthy flora, rich in bacteria that produce lactic acid. The presence of healthy intestinal flora improves the development of the intestinal barrier and/or maintains its integrity, stimulates the formation of mucus, inhibits pathogenic bacteria and stimulates the immune system.

Application WO No. 0008984 refers to not digested mixture of hydrocarbons for recovery and increase the number of microorganisms present in the healthy microflora of the large intestine.

Before the birth of the intestinal tract of the child in the normal sterile. During passage through the birth canal of the intestinal tract of the child colonized vaginal and intestinal bacteria of the mother, which leads to the colonization of the gastrointestinal tract Rebbe is ka bacteria in the environment.

Natren® produces probiotic product Life Start®, which is designed specifically for children and is suitable for children born by caesarean section. Life Start® made with Bifidobacterium infantis. As Life Start® contains only one species of Bifidobacterium, benefits for the child will be very limited.

The invention

The authors of the present invention have found that children born by caesarean section, have intestinal flora that differs from the intestinal flora of children born through the birth canal. In particular, children born by caesarean section, have reduced the rate of colonization of Bifidobacteria and have less diverse species of Bifidobacteria intestinal flora than children born through the birth canal, in particular, no Bifidobacteria breve, Bifidobacteria longum, Bifidobacteria infantis and Bifidobacteria bifidum.

It was further discovered that the intestinal flora of children born by caesarean section, has a low content of Bifidobacteria compared with the intestinal flora of children born through the birth canal. Additionally, it was found that the intestinal flora of children born by caesarean section, 6 weeks after birth has a high content of (unwanted) Esherichia coly.

The authors of the present invention found that the above defects of the intestinal Flo is s children can be eliminated by introducing not digested oligosaccharides child born by caesarean section, preferably included in the diet of a child born through caesarean section. In particular, it is found that the introduction of not digested oligosaccharides leads to increased levels of bifidobacteria in the child born by caesarean section, and also reduces the content of E. coli. The elimination of such defects causes better health and prevents and/or treats various diseases.

Healthy and fully developed intestinal flora has important physiological effects. One important aspect is the reduction in frequency (gastrointestinal) infections. As in children born by caesarean section, there is no healthy flora, prevention of infection is especially important for these children. These children are usually born in the hospital, what is the risk of pathogenic contamination due to the presence of hospital-acquired (nosocomial) bacteria. Additionally, poor development of healthy intestinal flora causes more rapid colonization of pathogenic bacteria compared to the situation when the intestinal tract of the child was settled by the parent bacteria.

The present invention, in particular, aimed at reducing the number and severity (gastrointestinal) infections in children born by caesarean section,(i) stimulation of the growth of beneficial bacteria, preferably bacteria that produce lactic acid; (ii) reducing the growth of pathogenic bacteria; and/or (iii) a decrease in the adhesion of pathogenic bacteria to intestinal epithelial cells and/or the mucous membrane of the intestine.

The authors of the present invention have found that (gastrointestinal) infections can be prevented and cured neperevershenymy the oligosaccharides, in particular, galactooligosaccharide. These nevereverever oligosaccharides suitable for enteral (particularly oral) administration, making them easy to include in feeds for baby food. Presents nevereverever oligosaccharides reduce the frequency of infections as well as reduce the severity of infections, due to the reduced intestinal concentrations of pathogenic microorganisms, including Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus haemolyticus, Streptococcus, Clostridium difficile, Bacilus subtilis, Pseudomonas aerugenosa, Enterobacter, Klebsiella, Acinetobacter, Proteus, Aeromonas, Escherichia coli.

The prevalence and severity of infection in children born by caesarean section, may be additionally reduced by providing a mixture of at least two not digested oligosaccharides that differ in structure and/or degree of polymerization (DP), and also an additional provision, in addition to nevereverever neutral oligosaccharide, sour ol is Kosharica, in particular oligosaccharide consisting of residues of uronic acid. The mixture is not digested oligosaccharides that differ in structure and/or degree of polymerization, stimulates the development of healthy putting flora. Especially suitable galactooligosaccharide and/or fructo-oligosaccharides were found to stimulate the growth of B. Longum, B. Breve and/or B. Infantis (example 2). Oligosaccharides consisting of residues of uronic acid, prevent adhesion of pathogenic bacteria to the intestinal wall, thus preventing and/or curing infections caused by pathogens.

In addition to reducing the frequency of infections, and other disorders in children born by caesarean section, prevent and/or treat presents way. In particular, such disorders as allergies and eczema prevent and/or treat the growth of healthy intestinal flora.

In an additional embodiment, the present invention can be appropriately introduced into practical use through the inclusion of active ingredients of the present invention in the composition of the food composition. Such a composition can be introduced easily to the child born through caesarean section.

A DETAILED DESCRIPTION of the PREFERRED embodiments

This method provides the use of the computer the positions, containing nevereverever oligosaccharides, for the production of compositions for (i) treatment and/or prevention of disorders in children born by caesarean section and/or (ii) improve the overall condition of children born by caesarean section.

In an additional embodiment, the present invention relates to method (i) treatment and/or prevention of disorders in children born by caesarean section, and/or (ii) improve the health of children born by caesarean section; this method includes the introduction of neperebrodivsego oligosaccharide child, born by caesarean section, preferably, the method for prevention and/or treatment of infection; and/or preventing and/or treating allergies in children born by caesarean section.

In an additional embodiment, the present invention relates to a method of promoting the development of a healthy intestinal flora and/or reduce the prevalence of enteric pathogens in children born by caesarean section, which includes the stages of: a) mixing (I) food or pharmaceutically acceptable liquid; and II) a dry composition, in which the dry composition II contains nevereverever oligosaccharide, and (b) introducing the composition obtained in stage a), the child.

Even complements the linen embodiment, the present invention relates to a method of promoting the development of a healthy intestinal flora and/or reduce the prevalence of enteric pathogens in children born by caesarean section, which includes the introduction of child compositions containing nevereverever oligosaccharide.

In an additional embodiment, the present invention relates to a method of providing power of a child born by caesarean section, where the method includes the stages of: a) mixing the composition containing nevereverever oligosaccharide, power input to the child born through caesarean section; and (b) introducing the composition obtained in stage a), a child born by caesarean section. The invention also relates to compositions containing at least 5 wt.% neperebrodivsego oligosaccharide based on the dry weight of the composition, and at least 1 wt.% oligosaccharide consisting of uronic acid residues, based on the dry weight of the composition.

Cesarean section

The present invention relates to enteral introduction of a child born through caesarean section, the composition comprising nevereverever oligosaccharides. Caesarean section (C-section) is a surgical procedure in which the baby is removed through an incision made in the mother's abdominal wall and then through an incision of the uterus. A caesarean section is usually performed if it is safer for mother and baby h is m birth through the birth canal. On the other hand, a woman may choose cesarean section more likely than the birth of the child through the birth canal.

Nevereverever oligosaccharides

The present invention provides nevereverever oligosaccharides, which are preferably stimulate the development of intestinal bacteria that produce lactic acid, in particular Bifidobacteria and/or Lactobacilli.

The term "oligosaccharide", used in the present invention refers to saccharides with a degree of polymerization (DP) from 2 to 250, preferably a DP of 2 to 100, more preferably from 2 to 60, more preferably from 2 to 10. If the oligosaccharide with a DP of 2 to 100 included in the present composition, this implies compositions that contain oligosaccharides with a DP between 2 and 5, DP between 50 and 70 and DP from 7 to 60. The term "nevereverever oligosaccharide used in the present invention refers to oligosaccharides, which remain undigested or only partially digested in the intestine by the action of acids or digestive enzymes present in the human upper digestive tract (small intestine and stomach), but which are fermented by intestinal flora of man. For example, sucrose, lactose, maltose and maltodextrin is considered digestible. Preferably nevereverever oligosaccharide is nevereverever the th neutral oligosaccharide. The term "neutral oligosaccharide used in the present invention, means oligosaccharides, in which more than 75% sharidny units selected from the group consisting of glucose, fructose, galactose, mannose, ribose, ramnose, arabinose and xylose, preferably more than 85%, more preferably more than 95%, even more preferably more than 99%. Preferred neutral oligosaccharides are transplantological and fructo-oligosaccharides.

Preferably this nevereverever oligosaccharide is a prebiotic oligosaccharide. The term "prebiotic oligosaccharide" refers nevereverever oligosaccharide, which favorably affects the host by selective stimulation of growth and/or activity of one or a limited number of probiotic bacterial species in the colon.

Preferred real nevereverever oligosaccharide is soluble. The term "soluble"used in this document in relation to the polysaccharides, fibers or oligosaccharides, means that the substance is at least soluble in the appropriate manner described by L. Prosky et al., Assoc. Off. Anal. Chem. 71, 1017-1023 (1988).

Preferred present composition includes at least one nevereverever oligosaccharide selected from the GRU is dust, consisting of galactooligosaccharides, not digested dextrins, xylooligosaccharides, arabinopyranoside, glucooligosaccharides (including gentillyschild and cyclodextrins), chitooligosaccharides, frukooligosaharidov, mannooligosaccharide, isomaltooligosaccharide, fructo-oligosaccharides (including inulin), galactopyranoside, glucoronolactone and arabinopyranoside; more preferably, at least galactooligosaccharide and/or fructo-oligosaccharides, more preferably, at least galactooligosaccharide.

The term "fructooligosaccharide"used in this document, refers to nevereverever the polysaccharide carbohydrate comprising a chain of at least 2, United at the β-position fructose chains with a DP of 2 to 250, preferably from 7 to 100, more preferably from 20 to 60. Preferably inulin is used. Inulin is sold under the trade name "Raftilin HP®", (Orafti). The average DP of the presented fructooligosaccharide is preferably at least 7, more preferably at least 10, preferably below 100. Used oligosaccharide preferably contains (most of) fructose units associated with β(2→1)-connection. Other terms for oligosaccharides include inulin, fructooligosaccharide, polymaltose and oligofructose. This comp is position preferably includes fructo-oligosaccharides with a DP of 2 to 100.

Nevereverever dextrins are resistant to digestion of the maltodextrins or resistant to digestion of Polydextrose, which preferably has a DP of 10 to 50, preferably from 10 to 20. Nevereverever dextrins preferably contain α (1→4), α (1→6)-linkages 1→2 and 1→3. Nevereverever dextrins, for example, sold under the trade name "Fibersol 2®" Matsutami Industries or Litesse®Danisco.

The authors of the present invention found that galactooligosaccharide can be advantageously used in the present composition, as these oligosaccharides are particularly effective in stimulating the growth of Bifidobacteria. Therefore, in a preferred embodiment, the present composition includes galactooligosaccharide. The term "galactooligosaccharide"used in this document, refers to nevereverever the oligosaccharide in which at least 30% sharidny units are galactose units, preferably at least 50%, more preferably at least 60%. The present composition preferably contains galactooligosaccharide with DP 2-100, more preferably 2-10 DP. Preferably sugars of galactooligosaccharide are linked in the β-position, as in the case of oligosaccharides of human milk.

Predpochtitel is but the real composition includes galactooligosaccharide, selected from the group consisting of transplantationfollow, lacto-N-tetraone (LNT) and lacto-N-neoteroi (neo-LNT). In a particularly preferred embodiment, this method includes the introduction of transplantologiia ([galactose]n-glucose, in which n is an integer between 1 and 60, for example, 2, 3, 4, 5, 6,..., 59, 60; preferably n is an 2, 3, 4, 5, 6, 7, 8, 9 and/or 10). Transplantological (TOS) is represented, for example, sold under the trade name VivinalTM(Borculo Domo Ingredientes, Netherlands).

The present composition preferably comprises from 0.5 to 75 g not digested oligosaccharides per 100 g dry mass, preferably from 0.5 to 50, the Present composition preferably contains from 0.1 to 75 g of galactooligosaccharides 100 g dry weight, preferably from 0.1 to 50 g

The present method preferably includes an introduction portion, containing from 0.05 to 25 g neperebrodivsego oligosaccharide, preferably from 0.1 to 5, the Present method preferably includes an introduction portion, containing from 0.05 to 25 g galactooligosaccharides, preferably from 0.1 to 5 g galactooligosaccharides.

The authors present invention also found that a mixture of long-chain not digested (neutral) and short-chain oligosaccharides not digested (neutral) oligosaccharides si is ergina stimulates the growth of healthy intestinal flora, in particular Bifidobacteria, and reduce the prevalence of E. coli in children born by caesarean section.

This composition thus preferably includes at least two not digested (neutral) of the oligosaccharide with different average degrees of polymerization (DP). Preferably the mass ratio:

A. (nevereverever (neutral) oligosaccharides with a DP of 2 to 5) nevereverever (neutral) oligosaccharides with DP 6, 7, 8 and/or 9)>1; and/or

b. (nevereverever (neutral) oligosaccharides with DP 10 to 60) nevereverever (neutral) oligosaccharides with DP 6, 7, 8 and/or 9)>1.

Preferably, both the mass ratio was higher than 2, even more preferably above 5.

To further improve this nevereverever oligosaccharide preferably has a relatively high content of short-chain oligosaccharides, as they strongly stimulate the growth of Bifidobacteria. Thus, preferably at least 10 wt.% not digested oligosaccharides in the present compositions have a DP of 1 to 5 (for example, 2, 3, 4 and/or 5) and at least 5 wt.% have a DP of 10 to 60. Preferably at least 50 wt.%, more preferably at least 75 wt.% not digested neutral oligosaccharides have a DP from 2 to 9 (for example, 2, 3, 4, 5, 6, 7, 8 and/or 9).

To improve the bioavailability of and stimulate the growth of many enteric organisms present composition preferably includes two not digested with various oligosaccharide structure. The present composition preferably contains at least two different not digested (neutral) of the oligosaccharide in which oligosaccharides are homologically sharidny links below approximately 90%, preferably below 50%, even more preferably below 25%, even more preferably below 5%. The term "gomologichnosti"used in the present invention, represents a cumulative percentage of the same Zaharenko link in various oligosaccharides. For example, oligosaccharide 1(OL1) has the structure of FRU-FRU-Glu-Gal and, therefore, contains 50% FRU (fructose), 25% Gal (galactose) and 25% Glu (glucose). Oligosaccharide 2 (OL2) has the structure of FRU-FRU-Glu and, therefore, contains 66% FRU, 33% Glu. Various oligosaccharides, thus, have homologically 75% (50% FRU + 25% Glu).

The present composition preferably contains galactooligosaccharide and fructo-oligosaccharides, more preferably transplantological with DP 2-7 and fructo-oligosaccharides with a DP between 10 and 100.

Oligosaccharides consisting of residues of uronic acid

The present composition preferably contains an oligosaccharide consisting of uronic acid residues, more preferably a combination of neperebrodivsego neutral oligosaccharide or oligosaccharide consisting of residues of uronic acid. Oli is saharid, consisting of residues of uronic acid, (optional) reduces the adhesion of pathogens to the intestinal epithelium and inhibits intestinal colonization by pathogenic microorganisms.

The term oligosaccharide consisting of residues of uronic acid used in this invention, denotes an oligosaccharide in which preferably at least 25%, preferably at least 50% of the monosaccharide units, represented in the oligosaccharide selected from the group consisting of hyaluronic acid, mannurone acid, iduronovoy acid, Rybarikova acid, galacturonic acid and glucuronic acid. In a preferred embodiment of the invention, the oligosaccharide consisting of uronic acid residues, contains at least 50% of the galacturonic acid based on the total number of units of uronic acid oligosaccharide consisting of residues of uronic acid. Oligosaccharides consisting of residues of uronic acid used in the invention, preferably derived from pectin, pectate, alginate, chondroitin, hyaluronic acid, heparin, heparan, bacterial hydrocarbons, sialogogues, fucoidan, focalisation and/or carrageenan, more preferably from pectin and/or alginate, even more preferably from pectin, and most preferably is from polygalacturonic acid. This oligosaccharide consisting of residues of uronic acid, is a preferred product of the degradation of pectin and/or product degradation of alginate. The preferred product of the degradation of pectin is hydrolyzed pectin (obtained by hydrolysis) and/or the lysate of pectin (derived beta-elimination). The product of the degradation of pectin preferably derived from pectin fruits and/or vegetables, more preferred Apple pectin, citrus pectin and/or sugar beet pectin. The product of the degradation of pectin preferably obtained in the presence of the lyase and/or differences of temperature and pressure, preferably in the presence of LiAZ, for example, beta-elimination. The product of the degradation of pectin is preferably lysate pectin.

Preferably the present composition contains an oligosaccharide consisting of residues of uronic acid with a DP of 2 to 250, more preferably a DP of 2 to 100, even more preferably a DP of 2 to 20. Preferably the present composition contains from 25 to 100 wt.%, more preferably from 50 to 100 wt.% oligosaccharide consisting of units of uronic acid with a DP of 2 to 250, more preferably a DP of 2 to 100, even more preferably a DP of 2 to 20.

Presents oligosaccharide consisting of uronic acid residues, preferably provided by enzymatic degradation of pectin in p is outstay the pectin lyase, pectin LiAZ, andprecautions and/or pectinase.

In a preferred embodiment, at least one of the end links hexuronic acid oligosaccharide consisting of residues of uronic acid has a double bond, which preferably is located between the C4and C5the provisions final balance hexuronic acid. The double bond of the end link hexuronic acid can be preferably provided by enzymatic hydrolysis of pectin in the presence of LiAZ.

In an additional embodiment, used a mixture of oligosaccharides consisting of residues of uronic acid, which have a different DP and/or contain unsaturated and saturated end links hexuronic acid. Preferably at least 5%, more preferably at least 10%, even more preferably at least 25% of the final links hexuronic acid oligosaccharide consisting of residues of uronic acids are unsaturated links hexuronic acid. As each individual oligosaccharide consisting of uronic acid residues, and includes only one unsaturated end link hexuronic acid, preferably less than 50% of the final links hexuronic acids are unsaturated residues of hexuronic the th acid (i.e. contain a double bond). A mixture of oligosaccharides consisting of residues of uronic acids, preferably contains from 2 to 50% unsaturated end links hexuronic acid based on the total number of end links hexuronic acid, preferably from 10 to 40%.

Oligosaccharide consisting of uronic acid residues, can be derived. Oligosaccharide consisting of uronic acid residues, can be methoxycarbonyl and/or emitirovannykh. In one preferred embodiment, the oligosaccharide consisting of uronic acid residues that differ in the degree of methoxylation of approximately 20%, preferably approximately 30%, even more preferably about 70%. Used in this document the degree of methoxylation (also referred to as DE or "degree of esterification") is intended to indicate the extent to which free carboxylic acid group contained in the oligosaccharide consisting of residues of uronic acid, tarifitsirovana (e.g., methylated). In another preferred embodiment, the oligosaccharide consisting of uronic acid residues, have a degree of methylation of about 20%, preferably approximately 30%, even more preferably about 70%.

The present composition preferably contains from 0.1 to 10 g of oligosaccharide, consisting of uronic acid residues, with a DP of 2 to 250 per 100 g dry weight of the present composition, more preferably from 0.05 to 6 g, even more preferably from 0.2 to 2 g per 100 g dry weight. The present composition preferably contains from 0.01 to 10 g of oligosaccharide consisting of remnants of the galacturonic acid, with a DP of 2 to 250 (more preferably a DP of 2 to 100) 100 g dry weight of the present composition, more preferably from 0.05 to 6 g, even more preferably from 0.2 to 2 g

Oligosaccharides consisting of uronic acid residues, preferably not digested in the upper division of the human gastrointestinal tract and are water-soluble (the appropriate method, disclosed L. Prosky et al., Assoc. Off. Anal. Chem. 71, 1017-1023 (1988). Oligosaccharides consisting of uronic acid residues, preferably are fermented by intestinal flora. The oligosaccharides of the present invention, consisting of residues of uronic acid, successfully reduces the adhesion of pathogens to intestinal epithelial cells, thereby reducing colonization (nosocomial) pathogenic bacteria of the colon of a child born through caesarean section. Moreover, the oligosaccharides of the present invention, consisting of uronic acid residues, preferably stimulate the production of healthy intestinal flora and split, causing clicks the use of intestinal organic acids and decrease intestinal pH, that inhibits the growth of (nosocomial) pathogenic bacteria.

Bacteria that produce lactic acid

The present composition preferably contains bacteria that produce lactic acid, or alive, or dead. Bacteria that produce lactic acid, preferably presented in the form of mono - or mixed culture of live microorganisms. The present composition preferably contains 102up to 1013colony forming units (CFU) of bacteria that produce lactic acid per gram dry weight of the present composition, preferably 102up to 1012most preferably from 104up to 5×109SOME.

Preferably the present composition comprises bacteria of the genus Lactobacillus or Bifidobacterium. Preferably the composition contains at least one Bifidobacteria selected from the group consisting of B. breve, B. longum, B. infantis, B. catenulatum, B. pseudocatenulatum, B. adolescentis, B. animalis, B. gallicum, B. Lactis and B. Bifidum, but more preferably B. Breve, B. infantis, B. Bifidum, B. catenulatum, B. longum, more preferably B. Breve and B. longum, most preferably B. Breve. Preferably the composition comprises at least two different species of Bifidobacterium subspecies or strain. Preferably the present composition comprises at least one, more preferably at least two, more preferably at least three, the most is her preferably at least four different species of Bifidobacterium. Preferably the present composition comprises at least one, more preferably at least two, more preferably at least three, most preferably at least four different strains of Bifidobacterium. Preferably the present composition comprises at least B. Breve and B. longum. The above combinations, in General, are designed to increase the variety and/or number of microorganisms in the gut of a child born through caesarean section. Specified beneficial effect on the child, demonstrating improved health.

Preferably the present composition comprises Lactobacillus selected from the group consisting of L. casei, L. reuteri, L. paracasei, L. rhamnosus, L. acidophilus, L. johnsonii, L. lactis, L. salivarius, L. crispatus, L. gasseri, L. zeae, L. fermentum and L. plantarum, more preferable L. casei, L. paracasei, L. rhamnosus, L. johnsonii, L. acidophilus, L. fermentum and the most preferable L. paracasei. Even more preferred is a real composition comprising Bifidobacterium breve and Lactobacillus paracasei, because the growth of these bacteria is weakened in the intestines of children who are fed formula compared to breast-fed children. Additionally, increased bioavailability will have a stimulating effect on the General condition of the neonates born by caesarean section.

Long-chain polyunsaturated fatty key is lots

The present composition preferably contains long-chain polyunsaturated fatty acids (LC-PUFA). LC-PUFA are fatty acids or fatty allowee chain length from 20 to 24 carbon atoms, preferably 20 or 22 carbon atoms, containing two or more unsaturated bonds. More preferably the present invention provides eykozapentaenovuyu acid (EPA, n-3), docosahexaenoic acid (DHA, n-3) and/or arachidonic acid (ARA, n-3). Mentioned LC-PUFA effectively reduce the permeability of the intestinal barrier. Decrease intestinal permeability decreases the incidence of infection and/or reduces the penetration of allergens. Therefore, the introduction of EPA, DHA and/or ARA in the present composition improves the integrity of the intestinal barrier, which is critical for children born by caesarean section, as described children have less developed intestinal flora and therefore less Mature intestinal barrier. The introduction of these LC-PUFA will additionally facilitate (synergistically) to reduce the frequency and severity of infections and allergies.

As EPA, DHA and/or ARA already effective at low concentrations, to reduce the permeability of the intestinal barrier, the content of LC-PUFA with 20 and 22 carbon atoms in the present composition preferably does not exceed 15 wt.% total fat content, predpochtitel shall not exceed 10 wt.%, even more preferably does not exceed 5 wt.% total fat content. Preferably the present composition contains at least 0.1 wt.%, preferably at least 0.25 wt.%, more preferably at least 0.6 wt.%, even more preferably at least 0.75 wt.% LC-PUFA with 20 and 22 carbon atoms based on the total fat content. For the same reasons, the EPA content preferably does not exceed 5 wt.% total fat content, preferably less than 1 wt.%, but is preferably at least 0.03 wt.%, more preferably at least 0.05 wt.% total fat content. The DHA content preferably does not exceed 5 wt.%, preferably does not exceed 1 wt.%, but is preferably at least 0.1 wt.% total fat content. Since it was found that ARA is particularly effective in reducing permeability, the present composition contains a relatively high amount, preferably at least 0.1 wt.%, even more preferably at least 0.25 wt.%, most preferably at least 0.35 wt.% total fat. The ARA content preferably does not exceed 5 wt.%, more preferably does not exceed 1 wt.% total fat. If the present composition for enteral administration contains EPA, DHA successfully added to the balanced action of ARA, i.e. to reduce the potential proinflammatory action of ARA metabolites. Over ARA metabolites can cause inflammation. Therefore, the present composition preferably contains ARA, EPA and DHA, in which the mass ratio of ARA/DHA is preferably approximately 0.25, preferably about 0.5, even more preferably about 1. The ratio is preferably less than 25, more preferably below 15. The mass ratio of ARA/EPA ranges from 1 to 100, more preferably from 5 to 20.

The present composition preferably contains from 5 to 75 wt.% polyunsaturated fatty acids, based on total weight, preferably from 10 to 50 wt.%.

The content of LC-PUFA, LC-PUFA with 20 and 22 carbon atoms, preferably not more than 3 wt.% total fat content as needed for a more complete resemblance to human milk. LC-PUFA can be provided as free fatty acids, in the form of triglycerides, in the form of diglycerides in the form of monoglycerides in the form of phospholipids or mixtures of the above. The present composition preferably contains at least one of ARA and DHA in the form of a phospholipid.

Nucleotides

Preferably the present composition contains nucleotides and/or nucleosides, more preferably nucleotides. Preferably, the composition includes citizen 5'-monophosphate, origin'-monophosphate, adenosine'-monophosphate, guanosine'-monophosphate and/or inosine'mon the phosphate, more preferably citizen'-monophosphate, origin'-monophosphate, adenosine'-monophosphate and inosine'-monophosphate.

Preferably the composition contains from 5 to 100 mg, more preferably from 5 to 50 mg, most preferably from 10 to 50 mg of nucleotides and/or nucleosides per 100 g dry weight of the composition. The presence of nucleotides and/or nucleosides successfully improves the development and maturation of the intestine in a child, which is crucial in children born by caesarean section. Nucleotides and/or nucleosides additionally stimulate the immune system, thereby improving protection against high workload of the intestine by pathogenic microorganisms, such as E. coli. Nucleotides and/or nucleosides are acting synergistically with other ingredients of the present composition.

A mixture of baby food

The present composition is preferably introduced enterline, more preferably orally.

This song is a nutrient mixture, preferably a mixture of baby food. The present invention can be successfully used as nutrition for children. The present composition preferably comprises a lipid component, a protein component and a carbohydrate component, and preferably is introduced in liquid form. The present invention includes all the I dry food (for example, powders), which is accompanied by instructions on how to mix this dry food mixture with a suitable liquid (e.g. water).

The present invention successfully provides a composition in which the lipid component is from 5 to 50% of the total calories, the protein component is from 5 to 50% of the total calories and the carbohydrate component is from 15 to 90% of the total calories. Preferably, the present composition of the lipid component comprises from 35 to 50% of the total calories, the protein component comprises from 7.5 to 12.5% of the total calories and the carbohydrate component is from 40 to 55% of total calories. To calculate percent of total calories for the protein component must be calculated the total energy provided by protein, peptides and amino acids.

The present composition preferably contains at least one lipid selected from the group consisting of animal fat (excluding human fat and vegetable fats. Preferably the present composition comprises a combination of vegetable fats and at least one oil selected from the group consisting of fish oil, animal oil, algae oil, fungal oil and microbial oil. The present composition includes nevereverever oligosaccharides, excluding human milk.

The protein component used in food prep is ATA, preferably selected from the group consisting of the non-human animal proteins (preferably milk proteins), vegetable proteins (preferably soy protein and/or rice protein), free amino acids and mixtures thereof. Cow's milk is a source of nitrogen. The present composition preferably contains casein, whey, hydrolyzed casein and/or hydrolyzed whey protein. Preferably, the protein includes a protein, more preferably integral proteins bovine serum and/or whole casein proteins derived from cow's milk. Since this composition is suitable for use to reduce the allergic reaction in a child, the protein is preferably selected from the group consisting of hydrolyzed milk protein. Preferably the present composition contains hydrolyzed casein and/or hydrolysed whey protein, vegetable protein and/or amino acids. The use of the above proteins further reduces allergic reactions in children. Use listed gidrolizirovanny proteins successfully improves the absorption of food protein component of the immature gut of a child born through caesarean section.

The present composition preferably contains a carbohydrate selected from the group consisting of ugrozy, lactose, glucose, fructose, solids corn syrup, starch and maltodextrins, more preferred lactose.

Irregular bowel movements (e.g., constipation, stool insufficient, diarrhea) is an important problem in children born by caesarean section. This may be due to the high content of E. Coli in the faeces. Found that the stool can be reduced by the introduction of these not digested oligosaccharides in the liquid food with osmolarity of from 50 to 500 mOsm/kg, more preferably from 100 to 400 mOsm/kg Reduction defects of the chair is achieved by increasing colonization and development of healthy bowel flora.

Considering the above, it is also important that the liquid food is not possessed excessive caloric density, but could easily provide enough calories for human nutrition. Therefore, liquid food preferably has a caloric density of from 0.1 to 2.5 kcal/ml, even more preferred caloric density of from 0.5 to 1.5 kcal/ml, most preferred from 0.6 to 0.8 kcal/ml

Concentrated nevereverever oligosaccharides

Accordingly, an additional preferred variant implementation, the present invention relates to method of feeding the child born by caesarean section, in which the composition is, containing oligosaccharides, preferably concentrated compositions containing high amounts of oligosaccharides, either with the power input to the child born through caesarean section. Obtaining a concentrated form makes it possible to add these not digested oligosaccharides and artificial baby food and breast milk.

The present invention therefore relates to a method for providing nutrition of a child born by caesarean section, where the method includes the steps:

a) mixing the composition containing nevereverever oligosaccharides power input to the child born through caesarean section; and

b) introducing the mixture obtained in stage a), a child born by caesarean section.

Preferably with meals as mentioned in stage a) how is a baby milk formula or human breast milk. Composition containing nevereverever oligosaccharides used in stage a), is a concentrated composition is not digested oligosaccharides or, in other words, is a composition containing nevereverever oligosaccharides in high quantities.

Composition containing nevereverever oligosaccharides used in the Tadei a) in the above method, preferably contains at least 5 wt.%, preferably 10 wt.%, more preferably at least 25 wt.% not digested oligosaccharides, based on the dry weight of the composition, in which nevereverever oligosaccharides preferably selected from the group consisting of galactooligosaccharides, not digested dextrins, xylooligosaccharides, arabinopyranoside, glucooligosaccharides (including gentiopicroside and cyclodextrins), chitooligosaccharides, focalisation, mannooligosaccharides, isomaltooligosaccharides and fructo-oligosaccharides (including inulin). This composition can be improved by combining it with one or more of the components disclosed above, preferably one or more, or all, selected from the group of oligosaccharides, consisting of units of uronic acid, LC-PUFA, nucleotides and probiotic bacteria.

The present invention also relates to a composition which can be suitably used in the present method for mixing with food, for example, a composition that contains a high concentration neperebrodivsego neutral oligosaccharide. The composition contains at least 5 wt.% (preferably at least 10 wt.%) neperebrodivsego oligosaccharide, based on the dry weight of the composition, in which nevereverever oligosacharide preferably selected from the group consisting of galactooligosaccharides, not digested dextrins, xylooligosaccharides, arabinopyranoside, glucooligosaccharides (including gentiopicroside and cyclodextrins), chitooligosaccharides, focalisation, mannooligosaccharides, isomaltooligosaccharides and fructo-oligosaccharides (including inulin), and at least 1 wt.% (preferably at least 10 wt.%) oligosaccharide consisting of uronic acid residues, preferably defined above, based on the dry weight of the composition. The composition preferably contains galactooligosaccharide and/or fructo-oligosaccharides.

The composition is preferably designed to be added to one portion of the diet of the child. The total mass neperebrodivsego oligosaccharide in the present composition is preferably from 0.1 to 10 g, preferably from 0.2 to 5 g per serving. The composition is preferably packaged portions, i.e. one serving contains the same dose, preferably in the form of sachets. The portion of the composition preferably has a weight of from 0.5 to 25 g, preferably from 1 to 10,

Application

The present invention relates to (i) the treatment and/or prevention of disorders in children born by caesarean section, and/or (ii) stimulate the improvement of the General condition in children born by caesarean section. The disorder is predpochtitelno selected from the group consisting of intestinal disorders caused by a reduction bifidogenic flora. Preferably the disorder is selected from the group of infections and allergies. The present invention preferably relates to a method for prevention and/or treatment of infections and/or infectious disorders, in particular gastro-intestinal infections, more preferably for the treatment and/or prevention of infections caused by one or more microorganisms selected from the group consisting of Staphylococcus (especially S. aureus, S. epidermidis, S. Haemolyticus), Streptococcus (especially Streptococcus group b), Clostridium (especially C. Difficile), Bacilus (especially B. Subtilis), Pseudomonas (especially P. Aerugenosa), Enterobacter, Klebsiella, Acinetobacter, Proteus, Aeromonas, Escherichia coli, preferably Escherichia coli (E. coli).

Preferably, the present composition used in the method of treatment and/or prevention of intestinal infections, urinary tract infections, intestinal inflammation and/or prevention of diarrhea in children born by caesarean section. Preferably the present composition used in the method of modulating the immune system in children born by caesarean section. Preferably the present composition used in the method of modulating the immune system, preferably in the protection of the child from allergies.

The present composition is preferably administered to the child born through caesarean section,in the first year of life, preferably within 3 months after birth, more preferably within two weeks after birth, more preferably within 100 hours, more preferably within 72 hours, most preferably within 48 hours after birth.

The present invention also relates to a method of stimulating the development of a healthy intestinal flora of the child, including the stage of (A) mixing (I) food or pharmaceutically acceptable liquid; and (II) a dry composition, in which the dry composition II contains nevereverever oligosaccharides; and stage C) introducing the composition obtained in stage a child is born by caesarean section.

The introduction of this song is better intestinal flora and/or the formation of organic acids as metabolic end products of microbial fermentation. Increasing the amount of organic acids causes an increase of mucus production, improvement, maturation of the intestine and/or improvement of the intestinal barrier. Thus, in an additional embodiment the present invention relates to a method of treatment and/or prevention of allergies (especially food allergies), atopic eczema (e.g. atopic dermatitis), asthma, allergic rhinitis, allergic conjunctivitis in children born by caesarean section, specify the first method involves the introduction of child songs, containing real nevereverever (neutral) oligosaccharides.

Moreover, the introduction of this composition enhances the immune system. In an additional embodiment of the present invention, thus, relates to a method of treatment and/or prevention of systemic infections, otitis media and/or respiratory infections in children born by caesarean section.

EXAMPLES

Example 1: Molecular features of intestinal microbiota children born through normal vaginal delivery, compared with children born through caesarean section.

In this the influence of the way of birth (caesarean section versus natural patrimonial ways) on the intestinal microbial composition on the third day of life studied using PCR amplification with species-specific nutrient media for ten species of Bifidobacterium, three Ruminococcus species and one species of Bacteroides.

Microbial DNA was extracted and analyzed according to Favier et. Al, Environ Environ 2002; 68:219-226 and Satokari et al, Appl Environ Environ 2001; 67:504-513; Satokari et al., " System Appl Microb 2003; 26:572-584.

The results of certain Bifidobacterium and other species in samples of faeces 21 newborn baby after a caesarean section presented on the third day of life, are given in table 1. Table 2 shows certain Bifidobacterium and other species in samples of faeces 21 of the newborn after birth che is ez birth canal, presented at the third day of life. There is no specific characteristic for species B. dentum, B. ngulatum, B. Lactis, Ruminococcus bromii, Ruminococcus callidus and Ruminococcus obeum obtained in the faeces of children born by caesarean section, as well as children born through the birth canal.

It can be concluded that the microbial flora of a child born through a caesarean section is different from the flora of a child born through the birth canal. Not only the number of bifidobacteria and other species is much lower, but also the species composition of the flora of children born by caesarean section, was less diverse. As Bifidobacterium is a dominant genus in the flora of the children, these results can also be generalized to reduce the number of intestinal bacteria and reduce the diversity of gut flora in children born by caesarean section, the greater the sensitivity of the intestine to colonization (nosocomial) pathogenic microorganisms.

These results demonstrate the successful use of the composition and method corresponding to the present invention, such as infant feeding practices of children born by caesarean section to reduce intestinal pathogens, stimulation of healthy intestinal flora and, therefore, prevent infection, stimulate a healthy immune system is s and the stimulation of the maturation of the intestine.

-
Table 1
Children born by cesarean section
NewbornB. breveB. infantisB. bifidumB. catenulatum groupB. adolescentisB. longumB. gallicumBacteroides fragilis
1--------
2-----++--
3--------
4-------
5--------
6--------
7--------
8--------
9--- -----
10------++-
11--------
12-------
13--------
16---- ----
17--------
18--------
19--------
20--------
21---- ---
22--------
23--------
(-) = no growth; (+/-) = weekly gain; (+) = positive growth; (++) = strong increase

Table 2
Children born through normal vaginal delivery
NewbornB. breveB. infantisB. bifidumB. catenulatum groupB. adolescentisB. longumB. gallicumBacteroides fragilis
1A-+/td> ---++--
2A+/--++++-++--
3A---+----
4A+/---++++--
5A+/--++++-++++-
6A-- +/-++-++--
7a--+/-++++---
8A++++-+++---
9a---++++--
10A++--++---
11a++-++ ++-++-+
12A++++-++-+
13A+/---+-+--
16A---++-+--
17A+/--++-+--
18a+/--++ -+--
19a+--+-+--
20A---+-+--
21A---++++--
22A-+-++-+--
23a+-++++- +--
(-) = no growth; (+/-) = weekly gain; (+) = positive growth; (++) = strong increase

Example 2: the Impact of not digested oligosaccharides on the flora of children born by cesarean section

Children were given infant formula, supplemented with 0.8 g/100 ml galactooligosaccharide (GOS) with an average DP between 2 and 7, and fructo-oligosaccharides (FOS, Raftilin HP)(GFSF-group), or a standard infant formula without not digested oligosaccharides (SF group).

It was determined the content of bifidobacteria in the faeces. The percentage of the genus Bifidobacterium as a percentage of the total number of bacteria in the first week amounted to 4.3% in children born by caesarean section (n=44), compared with 19.8% in children born by vaginal delivery (n=28). By week 6 the percentage of bifidobacteria was 12.3% in SF-the group of children born by caesarean section (n=21), and 17.2% in GFSF-group of children born by caesarean section (n=13). the pH of faeces SF-group of children born by caesarean section, was 7.2 compared with 6.5 GFSF-group of children born by caesarean section. The percentage of E. coli was 11.8% in SF-the group of children born by caesarean section, and amounted to 0% in GFSF-group of children born by caesarean section (table 3).

These results show that the introduction of not digested neutral oligosaccharides children born by caesarean section (GFSF-group), causes an increase bifidogenic flora and reduction of potentially pathogenic bacteria compared with children born by caesarean section, which had not received not digested oligosaccharides (SF group). Additionally, the results show a reduction in the number of E. Coli due to the introduction of not digested oligosaccharides. The results demonstrate the successful use of not digested oligosaccharides, in particular, galactooligosaccharides and fructo-oligosaccharides in the present compositions to further improve this therapy in children born by caesarean section.

Table 3
The percentage of Bifidobacterium in children born by vaginal delivery and by caesarean section, fed infant formula with (GFSF) and without (SF) not digested oligosaccharides
ChildrenBifidobacterium in the first week (%)Bifidobacterium after 6 weeks (%)Fecal pHE. coli (%)
Eating is the only childbirth 19,8
Caesarean section SF4,312,37,211,8
Caesarean section GFSF4,317,26,50

Example 3: bifidogenic influence not digested oligosaccharides

Children were given infant formula, supplemented with 0.8 g/100 ml galactooligosaccharide (GOS) with an average DP between 2 and 7, and fructo-oligosaccharides (FOS, Raftilin HP)(GFSF-group) or standard infant formula that does not contain digestible oligosaccharides (SF group).

It was determined the content of bifidobacteria in the faeces. The percentage of the Bifidobacterium genus, as a percentage of the total number of bacteria, to the 6th week was 47% in SF and 68% in GFSF-group, respectively, which demonstrates that GFSF-group, vskarmlivaniya mixture not digested carbohydrates, had more bifidogenic flora compared with the SF-group. Also in species content percentage of Bifidobacterium infantis was 22% in GFSF-group and 18% in the SF group, B. longum was 3.7% in GFSF-group and 2.9% in the SF group and B. breve was 3.7% in GFSF-group and 2% in the SF group. The results demonstrate the successful use of not digested oligosaccharides, in particular galactooligosaccharides and fructo-oligosaccharides, in the present compositions to further improve this therapy in children born by caesarean section.

Example 4: Composition for infants born by cesarean section

The composition of the mixture for baby food contains 100 ml of ready mix: 1.6 g protein, 3.6 g fat, 6.4g digestible carbohydrates (mainly lactose), 0.8 g neoslavery oligosaccharides, of which 0.54 g transplantationfollow, 0.06 g of inulin and 0.2 g of hydrolyzed pectin (obtained by hydrolysis of citrus pectin lyase). Packaging and/or accompanying documentation relevant product indicates that the product can be suitably used for a) preventing and/or treating infection in children born by caesarean section; (b) preventing and/or treating infections caused by E. Coli infection in children born by caesarean section; (c) preventing and/or treating allergies in children born by caesarean section; and/or (d) modulation of the immune system.

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

A small package that contains:

0.2 g of oligosaccharide consisting of residues of uronic acids is (approximately 2 wt.%, on the basis of dry mass);

2 g of galactooligosaccharide and 0.3 g fructooligosaccharide (approximately 20 wt.%, on the basis of dry mass);

- Bifidobacterium breve and Bifidobacterium longum, approximately 5*109CFU of each strain;

- filler.

1. The use of a composition comprising nevereverever oligosaccharides to obtain a composition for treatment and/or prophylaxis of disorders in children born by caesarean section, in which the disorder is selected from the group consisting of allergies, asthma, infections and atopic dermatitis.

2. The use of claim 1, wherein the infection is selected from the group consisting of infections caused by Esherichia coli, Streptococcus, Clostridium, Bacillus, Pseudomonas, Enterobacter, Klebsiella, Acinetobacter, Proteus, Aeromonas.

3. The use according to any preceding paragraph, where the composition comprises at least one nevereverever oligosaccharide selected from the group consisting of galactooligosaccharides, not digested dextrins, xylooligosaccharides, arabinopyranoside, glucooligosaccharides (including gentillyschild and cyclodextrins), chitooligosaccharides, focalisation, mannooligosaccharides, isomaltooligosaccharides, fructo-oligosaccharides (including inulin), arabinogalactans, glycogenolysis and galactopyranosides.

4. The use according to claim 1, where the composition contains from 0.5 to 75 g neverever the excavated oligosaccharide 100 g dry weight of the composition.

5. The use according to any one of claims 1 or 2, where the composition comprises galactooligosaccharide and/or fructo-oligosaccharides.

6. The use according to any one of claims 1 or 2, where the composition comprises a lipid component, a protein component and a carbohydrate component, where the lipid component provides 5 to 50% of all calories, specified the protein component provides 5 to 50% of all calories specified carbohydrate component provides from 15 to 90% of all calories.

7. The use according to any one of claims 1 or 2, where the composition comprises nevereverever neutral oligosaccharides and uronic acid oligosaccharides.

8. The use according to any one of claims 1 or 2, where the composition contains long-chain polyunsaturated fatty acids and/or nucleotides.

9. The use according to any one of claims 1 or 2, where the composition is administered to the child within one week after birth, preferably within 100 hours after birth.

10. The use of a composition comprising nevereverever oligosaccharide to obtain a composition (i) treatment and/or prophylaxis of disorders in children born by caesarean section and/or (ii) improve the health of children born by caesarean section, in which:
a) the composition comprises at least one nevereverever oligosaccharide selected from the group consisting of galactooligosaccharides, neverever is by dextrins xylooligosaccharides, arabinopyranoside, glucooligosaccharides (including gentillyschild and cyclodextrins), chitooligosaccharides, focalisation, mannooligosaccharides, isomaltooligosaccharides, fructo-oligosaccharides (including inulin), arabinogalactans, glycogenolysis and galactopyranoside; and/or
b) the composition contains from 0.5 to 75 g neperebrodivsego oligosaccharide 100 g dry weight of the composition.

11. The use of claim 10, where the composition comprises galactooligosaccharide and/or fructo-oligosaccharides.

12. The use of claim 10 or 11, where the composition comprises a lipid component, a protein component and a carbohydrate component, where the lipid component provides 5 to 50% of all calories, specified the protein component provides 5 to 50% of all calories specified carbohydrate component provides from 15 to 90% of all calories.

13. The use of claim 10 or 11, where the composition comprises nevereverever neutral oligosaccharides and uronic acid oligosaccharides.

14. The use of claim 10 or 11, where the composition contains long-chain polyunsaturated fatty acids and/or nucleotides.

15. The use of claim 10 or 11, where the composition is administered to the child within one week after birth, preferably within 100 hours after birth.

16. Composition containing Myung is our least 5 wt.% neperebrodivsego oligosaccharide, on the basis of the dry weight of the composition, and at least 1 wt.% oligosaccharide consisting of uronic acid residues, based on the dry weight of the composition, in which the total mass not digested oligosaccharides ranging from 0.1 to 10 g per serving.

17. A composition comprising at least 5 wt.% neperebrodivsego oligosaccharide, based on the dry weight of the composition, and at least 1 wt.% oligosaccharide consisting of uronic acid residues, based on the dry weight of the composition, and containing 5-100 mg nucleotides per 100 g dry weight of the composition.

18. A composition comprising at least 5 wt.% neperebrodivsego oligosaccharide, based on the dry weight of the composition, and at least 1 wt.% oligosaccharide consisting of uronic acid residues, based on the dry weight of the composition, and containing from 102up to 1013CFU bacteria per gram dry weight of the composition.



 

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6 cl, 3 tbl, 2 dwg, 3 ex

FIELD: food industry.

SUBSTANCE: probiotic composition for infant food includes Bifidobacterium breve, undigestible saccharide A and undigestible saccharide B with a degree of polymerisation between 2 and 200, additionally contains Lactobacillus paracasei. The composition has a viscosity 1-6 MPa·s, a caloric content 10 and 250 kcal per 100 ml. The said composition is applied for food composition production for usage in a method for provision of infant food, for production of a composition for prophylactic and/or treatment of gastrointestinal diseases, immune diseases and/or endocrinopathy, for prophylactic and/or treatment of allergy, atopic dermatitis, eczema and/or infection.

EFFECT: invention ensures possibility to imitate infant indestinal flora at breastfeeding, optimal composition caloric content promotes to reduce diarrhea, immune diseases, endocrinopathy and allergy.

17 cl, 1 dwg, 4 tbl, 3 ex

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