Protein-free infant food

FIELD: food industry.

SUBSTANCE: this invention covers food for 0-36 month aged infants. A composition comprising free amino acids as a single source of protein, source of fat acids comprising long-chain polyunsaturated fatty acids (LCPUFA), source of carbonhydrates comprising assimilable and non-assimilable carbonhydrates and bifidus bacteria was proposed for treatment of the patients suffering from tormina, astriction, snivel, sniffle, vomit, diarrhea, feces cruentae, mucus in defecation, spots, eczema, gastroesophageal reflux, eosinophilic esophagitis or asthma, allergy for cow milk and/or intolerance to dietary protein, and/or infections. Herewith, non-assimilable carbonhydrates are chosen from milk protein-free source, and bifidus bacteria are dietary protein-free, and the whole composition is essentially intact protein-free. Besides, assimilable carbonhydrate component contains less than 2 mass percent of lactose from overall assimilable carbonhydrates. Fat component includes 0.1-5 mass percent of LCPUFA from overall fat acids content. As an alternative, this composition is applied for stimulation of immune system maturation of the infants suffering from atopic diseases.

EFFECT: improvement of infant health without risks of adverse allergic reaction.

25 cl, 2 dwg, 3 tbl, 1 ex

 

The present invention relates to improve the health of babies by taking baby food on the basis of amino acids.

The breast-feeding is the preferred method of infant feeding. However, often after an initial period of breast-feeding babies stop it, and then the diet of an infant contains basically only infant formula (baby food).

However, a small group of infants breast-feeding or traditional baby food causes negative reactions, such as pain and allergic reactions. People who suffer from allergies may experience problems with digestion or metabolism of certain substances in the food composition, which in turn leads to intestinal allergic reactions or systemic allergic reactions. Allergic reactions are mainly caused by the protein fraction of the food product. To reduce the undesirable effects often require significantly change the diet.

To prevent allergic reactions to protein prescription in the composition of the mixture for baby food using hydrolyzed milk protein, amino acids and non-dairy proteins, such as soy protein and other nutrients do not cause allergic reactions.

Known compositions of mixtures for infants PI the project, including amino acids as nitrogen source, which include FeedingTMfor patients suffering from allergies, disorders of the gastrointestinal tract, eczema, syndrome of inadequate intake or digestive problems.

In the prior art uses a small number of different sources of nutrients to prevent allergens prescription in the mix for baby food when you add these ingredients. However, the drawback is that infants are deprived of the positive impact of these additional ingredients.

In WO 2005/039319 describes the use of synbiotics in a mixture of baby food, including protein gidrolizovannogo form, which reduces the risk of allergies (page 11, lines 35-37).

In WO 2006/091103 describes a nutritional composition comprising synbiotics for the treatment and prevention of immunological disorders, including allergies. Describes that the use of hydrolyzed protein and/or free amino acids reduces the risk of allergies. The aim of the present invention is to improve preparations mixtures baby food for this risk by providing additional nutritional value, without entering in the composition of allergens.

The authors of this izobreteniya, what if the original composition of the mixture for baby food contains a variety of free amino acids without intact protein, it is not predictable for the development of intestinal flora. Instead of bifidobacteria and lactobacilli, which is the dominant flora of infants, normal breastfed in the gastrointestinal tract of infants receiving food products based on amino acids, prevails many other species of bacteria, including potentially pathogenic bacterial species.

The development of a healthy intestinal flora is very important for all babies, since babies are already suffering from the weakening of the immunological functions, which often leads to colic, constipation, soplivosti, wheezing, vomiting, diarrhea, blood in the stool, mucus in stool, rash or eczema.

The authors of the present invention recognize that the development of healthy flora is very important for babies receiving the diet containing mainly free amino acids as a protein source. Not wanting to be limited by any theory, the authors present invention recognize that a good flora, that is rich in bifidobacteria and Lactobacilli, essentially has a beneficial effect on maturation (mucosal) immune system. Good flora prevents the development of allergies or at least reduce the severity of allergies such ml is Denzel. Therefore, the authors of the present invention recognize the great importance and beneficial effects of the development of the flora on these babies.

Despite the limitations in prescription the mixture for baby food babies at risk, the authors of the present invention have found that certain selected food oligosaccharides, preferably fructans and/or degradation products of pectin can be added with a beneficial effect in the main prescription of the mixture to stimulate the development of flora, without the risk of any adverse allergic reactions.

In the basic formulation of the mixture do not use any products derived from milk, as this may lead to the introduction of milk allergens in the product. Therefore, prebiotic fiber of the present invention are carefully selected from well-known prebiotic fibers, in order to avoid adding non-allergenic composition of the milk or other intact and potentially allergenic proteins present in the fibers.

Unexpectedly, the authors of the present invention found that the widely accepted model for allergies when combining prebiotic fibers with probiotic bacteria (preferably bifidobacteria) is a synergistic effect, which consists in preventing allergies the Oh reaction. This synergistic effect is potentially very beneficial for babies, but can also be for adults.

In the drawings:

Figure 1 is an allergic response to various compositions tested in accordance with internationally recognized vaccine in the mouse model.

Figure 2 is a synergistic effect TD1 (Bifidobacterium breve) and dietary fiber (OS) on a murine model of Allergy to casein.

In a preferred embodiment, the present invention relates to the use of a composition comprising free amino acids as the sole source of protein, a source of fatty acids, including dinocephalia polyunsaturated fatty acids, a source of carbohydrates, including assimilated and unassimilated carbohydrates, and free from milk protein bifidobacteria, to obtain a composition for the treatment of individuals suffering from:

a. colic, constipation, soplivosti, wheezing, vomiting, diarrhea, bloody stools, mucus in stools, rashes, eczema, gastroesophageal reflux, eosinophilic esophagitis, or asthma;

b. of cow's milk Allergy and/or intolerance to dietary protein; and/or

c. infections where not assimilated carbohydrates are selected from a source free of milk protein, and the entire composition is essentially free from the intact protein.

Used herein, the term "sole source of protein" means that the song according to the present invention preferably contains, at least 99 wt.% amino acids from just protein, preferably at least 99,5 more preferably at least about 99.9 wt.%.

Additionally, the present invention relates to compositions comprising a protein component, a fat component, a digestible carbohydrate component, not assimilated carbohydrate component and bifidobacteria, where:

a) the protein component contains more than 99 wt.% free amino acids of all proteins and include, at a minimum, the following amino acids: alanine, arginine, aspartic acid, cysteine, glycine, histidine, isoleucine, leucine, methionine, Proline, serine, threonine, tryptophan, tyrosine, valine and glutamine;

(b) digestible carbohydrate component contains less than 2 wt.% lactose from all digestible carbohydrates;

c) not assimilated carbohydrate component comprises soluble fructan with an average degree of polymerization (SP) from 2 to 200 and soluble galacturonic acid with an average SP between 2 and 200; and

d) the fat component comprises from 0.1 to 5 wt.% LCPUFA (dinocephalia polyunsaturated fatty acids of the total fatty acids.

As shown in figure 1, the combination dinocephalia soluble fructans (LFOS) with acidic oligosaccharides (AOS), which in this case is hydrolyzed pectin, works as bifidobacteria when tested in the mouse model. It is clear, however, that if the oligosaccharide is to combine with bifidobacteria, the effect is greatly increased.

In a preferred embodiment of the invention, the nutritional composition includes unassimilated fiber and bifidobacteria, because this composition gives the best results in the mouse model for allergies (see Figure 1). Preferably useBifidobacteria breve.

Not assimilated carbohydrates

Fructans are neutral oligosaccharides on the basis of fructose (>50% mnoznych units are fructose), preferably inulin, fructan and/or fructo-oligosaccharides, most preferably a mixture of dinocephalia of fructo-oligosaccharides ((lcFOS)) with an average SP of 10 to 60 and karatkievich of fructo-oligosaccharides (scFOS) with an average SP from 3 to 10. A preferred variant of the invention includes a mixture of (lcFOS) and (scFOS) in the ratio 1:9, because this ratio is closer to the composition of breast milk oligosaccharides and provides effective stimulation of the growth of bifidobacteria in infants.

The method according to the present invention preferably includes an introduction portion, comprising from 0.05 to 25 grams unassimilated saccharides, preferably from 0.1 to 5 grams. Preferably the method according to the present invention includes from 0.05 to 25 grams (scFOS), preferably from 0.1 to 5 grams (scFOS). Preferably the method according to the present invention includes the introduction of unassimilated saccharides from 0.05 to grams per day, preferably from 0.1 to 5 grams per day.

The degradation products of pectin

Pectin is divided into two main categories: vysokomehanizirovannyh pectin, characterized by a degree of methoxylation above 50% and nizkokaloriyny pectin with a degree of methoxylation below 50%. Used herein, the term "degree of methoxylation (also indicated as SE or the "degree of esterification") refers to the number of free carboxylic groups of the acid contained in esterified (e.g., methylation) chain polygalacturonic acid. Preferably the pectin of the present invention is obtained from vysokomehanizirovannogo pectin.

Preferably, the pectin is characterized by a degree of methoxylation above 20%, preferably above 30%, even more preferably above 50%.

The pectin used in the method according to the present invention has an average degree of polymerization (SP) from 2 to 500, preferably from 10 to 250, and most preferably from 20 to 50. When using a mixture of pectins with different degrees of polymerization average SP acidic oligosaccharides of the mixture is preferably from 3 to 1000, more preferably from 3 to 250, even more preferably from 3 to 50. It was found that lower SP oligosaccharide improves palatability and reduces the viscosity of the product, if CI is small oligosaccharides add in liquid form.

Pectin is preferable to add from 0.1 to 100 grams per day, preferably from 0.4 to 50 grams per day, more preferably from 1 to 20 grams per day.

A preferred variant of the invention includes fructans and degradation products of pectin in a ratio of 50:50-95:5. Preferably, the ratio is 85:15 as the ratio of neutral and acidic oligosaccharides oligosaccharides present in human milk.

Probiotic bacteria

Probiotic bacteria suitable for use in the present invention, at least have a positive impact on a murine model of Allergy, as shown in the examples below. Additionally probiotics essentially should not contain food allergens. To obtain such probiotic bacteria requires special procedures or culture medium without intact protein.

Therefore, a preferred variant of the invention includes probiotic bacteria, essentially not containing intact protein food or food allergens, in particular, essentially no milk protein.

In a preferred embodiment of the invention, the probiotic bacteria are bifidobacteria. Even more preferably, the probiotic bacteria areBifidobacterium breve. Bifidobacteria have a very high the tolerance, inducyruya impact on the mouse model and, therefore, preferred. In particular, very effective Bifidobacterium breve.

In another preferred embodiment of the invention Bifidobacteria are not viable. This is an advantage because it increases the shelf life of food products, and immunomodulating activity of bacteria becomes independent from the number of live bifidobacteria. Experiments have shown that the immunostimulatory effects of nonviable bacteria similar and sometimes even better than the activity of living bifidobacteria.

The composition according to the present invention preferably includes from 102up to 1013colony forming units (CFU) of bacteria per gram dry weight of the composition of the present invention, preferably from 102up to 1012CFU, more preferably from 105up to 1010SOME, most preferably from 104up to 5×109SOME.

Amino acids

Amino acids can be used in compound feed for feeding young children and infants. However, the composition of amino acids in the mixture for the power supply preferably includes all of the essential amino acids, except for compositions for patients with phenylketonuria (PKU) and for patients with NEFCO birth defects of metabolism and preferably optimal for the power supply young children or infants. The authors of the present invention have found that the most optimal amino acid composition should be as close as possible to the amino acid composition of the protein fraction of milk. Preferred amino acid composition results are shown in Table 1 (see below). In a preferred embodiment of the invention the composition includes less than 1 wt.% peptides of the total mass of protein and more than 99 wt.% free amino acids from just protein, includes at least the following amino acids: alanine, arginine, aspartic acid, cysteine, glycine, histidine, isoleucine, leucine, methionine, Proline, serine, threonine, tryptophan, tyrosine, valine and glutamine.

The infant formula

The infant formula according to the invention comprises free amino acids as nitrogen source, grease, including a mixture of fats, including LCPUFA, and carbohydrates. Vitamins and minerals added in accordance with regulatory requirements.

Preferably the composition according to the invention is designed for feeding babies and comprises a lipid component, a protein component and a carbohydrate component. Preferably the lipid component provides 5 to 50% of all calories, preferably the protein component provides 5 to 50% of all calories and preferably the carbohydrate component provides from 15 to 90% of all calories. Suppose the equipment composition of the present invention is used as a mixture for infants, where the lipid component provides 35 to 50% of the total calories, the protein component provides from 7.5 to 12.5% of all calories and carbohydrate component provides from 40 to 55% of all calories. To calculate % of all calories for the protein component, you must take the total amount of energy provided by amino acids.

LCPUFA

The content of LCPUFA from 20 to 22 carbon atoms in the composition of the present invention preferably does not exceed 15 wt.% of the total fat content, preferably not more than 10 wt.%, even more preferably does not exceed 5 wt.% of the total fat content. Preferably the composition comprises at least 0.1 wt.%, preferably, at least 0.25 wt.%, more preferably, at least 0.5 wt.%, even more preferably at least 0.75 wt.% LCPUFA from 20 to 22 carbon atoms, the total fat content. Preferably the content of docosahexaenoic acid (DHA) does not exceed 5 wt.%, more preferably does not exceed 1 wt.% and is at least 0.1 wt.% from the total fat content. Since it was found that arachidonic acid (AA) effectively reduces the permeability of the intestinal impenetrable walls, the composition of the present invention includes a relatively high number, preferably at least 0.1 wt.%, even more preferably, at least 0.25 in the EU.%, most preferably, at least 0.5 wt.% from the total fat content. Preferably the content of AA does not exceed 5 wt.%, more preferably does not exceed 1 wt.% from the total fat content. Excess metabolites of AA can cause inflammation. However, the composition of the present invention preferably includes AA and DHA at a mass ratio of AA/DHA preferably above to 0.25, preferably above 0.5, more preferably above 1. Preferably the ratio is below 25.

LCPUFA preferably are non-fish derived from unicellular oil, available for example from Martek.

The preferred characteristics of the compositions of the present invention are shown in Tables 1-3.

Table 1
The amino acid compositions of the present invention
Amino acidUnitsThe content of AA as a percentage of the total AA content (g/100 g)
Baby 0-1 yearThe young child 1-10 years
Alag3,95 4,013,123,03
Argg6,997,0214.24 from13,91
Aspg6,54to 6.575,735,59
Cysg2,592,581,852,91
GIu acidg0,000,000,00
GIyg6,156,125,115,01
Hisgas 4.023,993,713,61
lsog6,156,12 5,115,01
Leug10,5610,518,548,32
Lysg7,197,196,256,11
Methg1,681,69as 4.023,90
Pheg7,517,477,106,93
Prog4,734,725,97of 5.82
Serg4,60br4.613,713,61
Thrg5,185,174,29 4,19
Tryg2,072,081,721,69
tyrg4,734,72the 1.441,40
VaIg6,746,745,42and 5.30
Carg0,060,060,100,12
taug0,190,200,170,17
GIug8,428,4312,3513,39
Totalg100100of 99.97100

Table 2
Infant formula for infants with allergies
The nutritional profile of the mixture for infants according to the present invention (powder)
UnitsContent/100 gContent/100 kcal
Equivalent proteing132,9
Energykcal455100
Nitrogeng2,1
Carbohydratesg4910,8
Fat (total)g235,1
(MST)%33
(LCT)% 67

Table 3
Content dinocephalia polyunsaturated (DCPN) fatty acids in the composition
% fatty acids
PreferredThe range of +/-25%
Arachidonic acid0,350,260,44
Docosahexaenoic acid0,200,150,25
Total DCPN0,550,410,69

The preferred limits of the oligosaccharide composition of about 0.4-1.2 g/100 ml, where 85 wt.% be (scFOS) and (lcFOS), and 15 wt.% is hydrolyzed pectin. Preferably the ratio (scFOS) to (lcFOS) is from 2 to 20, even more preferably the ratio is 9.

In one preferred variant of the embodiment of the present invention is free from milk protein and allergen complete powder is obrazow composition of the present invention, suitable for dilution with water, receiving enteral nutrition, including:

ComponentPer 100 g powder
Equivalent protein (g)13
The total amino acid content (g)15,5
Total fat (g)23
Sunflower oil (g)4
Fractionated coconut oil (g)7
Canola oil (g)4
Sunflower oil with a high content of olein (g)6,6
Oil ARASCOTM(g)0,21
Oil DHASCOTM(g)0,11
Carbohydrate: Maltodextrin (g)49
Prebiotic (g)5,33
(scFOS) (g)4,1
(lcFOS) (g) 0,43
KOS (g)0,8
Probiotic:B. Breve(colony forming units; CFU)1×1010
Other vitamins/minerals/trace mineralsBalance

The above composition provides about 455 kcal of energy per 100 g of powder.

The composition may be diluted with cold boiled water to receive the recommended concentration of 15% weight/volume.

Application

Preferably the composition is used to treat infants (essentially with atopic status)suffering from:

a. colic, constipation, soplivosti, wheezing, vomiting, diarrhea, bloody stools, mucus in stools, rashes, eczema, gastroesophageal reflux, eosinophilic esophagitis, or asthma;

b. of cow's milk Allergy and/or intolerance to dietary protein; and/or

c. infections.

Also preferably, the composition may be used to improve characteristics of stools in infants suffering from the above symptoms. Essentially, the arrangement is designed for babies aged 0 to 3 years. With some adaptations amino acid profile (see Table 1) the composition is also suitable for children aged 3 to 10 years. Infants with Allergy is th often suffer from diarrhea, but they also have constipation. Preferably, the composition that can be used for the prevention and treatment of these symptoms that includes dietary fiber according to the composition of breast milk, where the ratio (scFOS)/(lcFOS) is 9:1, and in addition there is a hydrolyzed pectin.

EXAMPLES

To determine the immunostimulating effects of oligosaccharides and probioticBifidobacterium breve(TD 1) conduct tests in accordance with internationally recognized vaccine in the mouse model (Figure 1) and allergic model (Figure 2).

Materials and methods immunization models

Female mice aged 6-8 weeks C57BI/6JOIaHsd from Harlan (Horst, the Netherlands) contain under normal conditions with a 12-hour cycle of night/day and with unlimited access to feed and water. All experiments approved by the independent Commission on animal experiments (DEC Consult, Bilthoven, the Netherlands).

Diets and drugs oligosaccharides

All animals receive the partially purified diets based on AIN-93G (Research Diet Services. Wijk bij Duurstede, the Netherlands). All additional oligosaccharide products replace with the same amount of total carbohydrates to support this option are the same. In addition, this approach allows to compare all the carbohydrate composition of different diets ensuring that the intestinal flora have the t minimal impact differences between the control and test diets on parameters such as the time of passage through the gastrointestinal tract and fluid retention. Oligosaccharides mixed with diet AIN-93G and pressed into pellets.

The vaccination Protocol and RKG response (reaction cutaneous hypersensitivity)

Experiments on vaccination is carried out with the use Influvac (influvac) (Solvay Pharmaceuticals, Weesp, the Netherlands) season 2002/2003. This vaccine inactivated influenza virus based on the selected antigens hemagglutinin (HA) and neuraminidase three strains of myxovirus influenza in a dose equivalent to 30 mg/ml HA per strain (90 [µg/ml HA in total). For all vaccines used oil adjuvant (Stimune, formerly known as Specol; Cedi-diagnostics, Lelystad, the Netherlands). First, mice are immunized and then re-Vaccinium subcutaneously (s/C) with a mixture of vaccine and adjuvant 1:1 with a total volume of 100 ál. Re-vaccination is carried out 21 days after the first vaccination. Experiments end in 10 days after re-vaccination. Blood samples (make retro - orbital puncture) taken before the first and second vaccination and at the end of the experiment. All experiments included a negative control group (specified as "false group"), the receiving injections of a mixture of 1:1 PBS and adjuvant total volume of 100 μl. False group never used for statistical comparison, they serve only to demonstrate the specificity of responses in tirovannyh vaccine. RKG reactions were induced in 9 days after re-vaccination s/C injection of 25 µl of Influvac in the ear both ears. The thickness of the ears was measured twice before vaccination and after 24 hours it using a digital micrometer (Mitutoyo Digimatic 293561, Veenendaal, the Nederlands). RKG response calculated by subtracting the basal ear thickness of the indicator 24 hours after vaccination.

Materials and methods used to model the Allergy on fiber of the cow milk

Chemicals

Casein and whey receive from DMV international, Veghel, the Netherlands.

The cholera toxin is available from Quadratech Diagnostics, Epsom, UK. PBS is available from Cambrex Bio Science, Verviers, Belgium. Buffer for sensitization of the surfaces Elisa kit available from Sigma, Alphen aan den Rijn, the Netherlands. Biotin labeled rat anti-mouse IgE, available from BD Biosciences, Alphen aan den Rijn, the Netherlands. All other chemical reagents are available from Sigma-Aldrich-Chemie, Zwijndrecht, the Netherlands.

Oral sensitization and introduction of substancesmice

Female mice that are free from specific pathogen, ranging in age from three to 5 weeks C3H/HeOuJ (n=4-6 per group) obtained from Charles River Laboratories (Maastricht, the Netherlands), include them in the diet for mice free of milk protein (Special Diets Services, Witham, Essex, UK) and kept them in vivarium, University of Utrecht (Utrecht University). Animals contain and use according to the requirements is to be Danish Commission on animal experiments. Mice sensibiliser intra-gastrale (d) 0.5 ml of homogenized casein (40 mg/ml PBS) with cholera toxin as adjuvant (CT, 20 μl/ml PBS)using a blunt needle. Control mice received only CT or PBS. Mice Vaccinium again weekly for 6 weeks, one week after the last sensitization mice injected/g 100 mg of casein.

Then collected and centrifuged blood samples (15 minutes at 13,500 rpm). Serum stored at -70°C. Mice killed by cervical vertebrae shift hour and a half later and/g vaccination.

Allergen-specific skin response

Acute allergen-specific skin response was measured after injection of a specific protein in the ear. Before and/g substances are introduced (t=0), control, sensitized casein mice do intradermal () injection in the left ear 20 ál of homogenized casein (0.5 mg/ml in PBS), respectively. In the right ear as a control inject 20 µl of PBS. Also mice that received CT and PBS injected casein in the ear and PBS as a control. The ear thickness was measured twice using a digital micrometer (Mitutoyo, Veenendaal, the Netherlands), through 0, 1, 4 and 24 hours after injection. Swelling of the ear with the allergen-specific response calculated by subtracting the basal (0 h) and control (right ear) the thickness of the measured parameter in three different the point in time (1, 4 and 24 h).

Measurement of serum immunoglobulin and protease-1 in the fat cells of the mouse

Concentrations of total IgE and levels of casein or specific serum IgE, IgGI and lgG2a determine serum dead mice using ELISA. Plate microlon (Greiner, Alphen aan den Rijn, the Netherlands) coated with casein buffer for sensitization of the surfaces or mouse anti-mouse IgE (1 μg/ml) in PBS for 18 hours at 4°C. Plates are washed and blocked for 1 hour with 5% BSA. Serum samples subjected to multiple dilutions and incubated for 2 hours at room temperature. Plates are washed 5 times and incubated with 1 mg of Biotin-labeled mouse anti-mouse IgE within half an hour at room temperature. After washing the strips incubated with horseradish peroxidase (HRP) for one hour, washed and identify o-phenylenediamine (OPD). The reaction is stopped 4M H2SO4and the absorbance measured at 490 nm on the reader for microplates Benchmark (Biorad, California, USA). Serum concentration of protease-1 in the fat cells of mice (mMCP-1) is determined, as described previously, using a commercially available ELISA kit (Moredun Scientific Ltd., Midlothian, UK).

The results of vaccination in a murine model shown in figure 1, from which it is clear that the combination of dietary fiber and 1 TD (=Bifidobacterium breve) provides the strongest impact on RKG response and much better than only TD1 or any other tested combinations.

The results are allergic to the casein in the mouse model is shown in Figure 2 and demonstrate that the combination of dietary fiber and 1 TD synergistically inhibits allergic RKG response to casein.

1. The use of a composition comprising free amino acids as the sole source of protein, a source of fatty acids, including dinocephalia polyunsaturated fatty acids, a source of carbohydrates, including assimilated and unassimilated carbohydrates and bifidobacteria, to obtain a composition for the treatment of individuals suffering from:
a. colic, constipation, soplivosti, wheezing, vomiting, diarrhea, bloody stools, mucus in stools, rashes, eczema, gastroesophageal reflux, eosinophilic esophagitis, or asthma;
b. of cow's milk Allergy and/or intolerance to protein food;
and/or infections
while not assimilated carbohydrates selected from a source free of milk protein, and bifidobacteria free of milk protein, and the entire composition is essentially free from the intact protein.

2. The use according to claim 1, in which the individual is a child aged 0 to 36 months.

3. The use according to claim 1 or 2, in which free amino acids from the total protein content include at least the following amino acids: alanine, arginine, aspartic acid is one cysteine, glycine, histidine, isoleucine, leucine, methionine, Proline, serine, threonine, tryptophan, tyrosine, valine and glutamine.

4. The use of a composition according to claim 3, in which amino acids provide 5 to 16 EN.% the whole composition, fats - 30 to 60 EN.%, of which LCPUFA provides 0.1-5 EN.%, and digestible carbohydrates 25-75 EN.%.

5. The use according to claim 4, in which LCPUFA provide 0.2 to 1 EN.% from the whole composition.

6. The use according to any one of claims 1, 2, 4, 5, which are not assimilated carbohydrates include (i) soluble fructan with an average degree of polymerization of from 3 to 200, and (ii) soluble galacturonic acid with an average degree of polymerization of from 3 to 200.

7. The use of a composition comprising free amino acids as the sole source of protein; a source of fatty acids, including dinocephalia polyunsaturated fatty acids;
the source of carbohydrates, including assimilated and unassimilated carbohydrates and bifidobacteria, for the production of compositions for the stimulation of the maturation of the immune system in infants with atopic conditions;
while not assimilated carbohydrates selected from a source free of milk protein, bifidobacteria free of milk protein, and the entire composition is essentially free from the intact protein.

8. The use according to claim 7, in which free amino acids from the total protein content include at least the following amino is islote: alanine, arginine, aspartic acid, cysteine, glycine, histidine, isoleucine, leucine, methionine, Proline, serine, threonine, tryptophan, tyrosine, valine and glutamine.

9. The use of a composition according to claim 7 or 8, in which amino acids provide 5 to 16 EN.% the whole composition, fats - 30 to 60 EN.%, of which LCPUFA provides 0.1-5 EN.%, and digestible carbohydrates 25-75 EN.%.

10. The use according to claim 9, in which LCPUFA provide 0.2 to 1 EN.% from the whole composition.

11. The use according to any one of claims 7, 8, 10, which are not assimilated carbohydrates include (i) soluble fructan with an average degree of polymerization of from 3 to 200, and (ii) soluble galacturonic acid with an average degree of polymerization of from 3 to 200.

12. Composition comprising a protein component, a fat component, a digestible carbohydrate component, not assimilated carbohydrate component and bifidobacteria, in which:
the protein component comprises free amino acids as the sole source of protein and contains at least the following free amino acids: alanine, arginine, aspartic acid, cysteine, glycine, histidine, isoleucine, leucine, methionine, Proline, serine, threonine, tryptophan, tyrosine, valine and glutamine;
digestible carbohydrate component contains less than 2 wt.% lactose from all digestible carbohydrates;
the fat component comprises from 0.1 to 5 wt.% LCPUFA of the total content of fatty acids differing by those who, that bifidobacteria are free from milk protein, not assimilated carbohydrate component is selected from a source free of milk protein, and includes soluble fructan with an average SP from 2 to 200 and soluble galacturonic acid with an average SP between 2 and 200.

13. The composition according to item 12, in which:
the fat component comprises from 0.2 to 1 wt.% LCPUFA of the total content of fatty acids.

14. The composition according to item 12, including unassimilated soluble fructan with an average degree of polymerization of from 2 to 200 and unassimilated soluble galacturonic acid with an average degree of polymerization of from 2 to 200.

15. The composition according to item 13, including unassimilated soluble fructan with an average degree of polymerization of from 2 to 200 and unassimilated soluble galacturonic acid with an average degree of polymerization of from 2 to 200.

16. Composition according to any one of p-15, including Bifidobacterium breve.

17. Composition according to any one of p-15, including arachidonic acid and/or docosahexaenoic acid.

18. The composition according to clause 16, including arachidonic acid and/or docosahexaenoic acid.

19. Composition according to any one of p-15, which as fructans use dinocephalia fructo-oligosaccharides FOS and korotkolapye fructo-oligosaccharides FOS.

20. The composition according to item 16, which as fructans use dinocephalia fructo-oligosaccharides f is C and korotkolapye fructo-oligosaccharides FOS.

21. The composition according to p, in which as fructans use dinocephalia fructo-oligosaccharides FOS and korotkolapye fructo-oligosaccharides FOS.

22. The composition according to claim 19, in which dinocephalia FOS has an average level SP from 10 to 60, and korotkolapye FOS has an average level SP from 3 to 10.

23. The composition according to claim 20 or 21, in which dinocephalia FOS has an average level SP from 10 to 60, and korotkolapye FOS has an average level SP from 3 to 10.

24. Composition according to any one of p-15, 18, 20-22, in which the product is a powder or liquid.

25. Composition comprising free amino acids as the sole source of protein, a source of fatty acids, including dinocephalia polyunsaturated fatty acids, a source of carbohydrates, including assimilated and unassimilated carbohydrates, and bifidobacteria for use in the treatment of an individual suffering from:
(a) colic, constipation, soplivosti, wheezing, vomiting, diarrhea, bloody stools, mucus in stools, rashes, eczema, gastroesophageal reflux, eosinophilic esophagitis, or asthma;
(b) cow's milk Allergy and/or intolerance to dietary protein; and/or
(c) infections
characterized in that are not assimilated carbohydrates are selected from a source free of milk protein, bifidobacteria free of milk protein, and the entire composition is essentially nobody from the intact protein.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to sulphonic 2-nitro-2-(3-aryl-1,2,4-oxadiazole-5-yl)ethane derivatives of formula I a-g la R=3-NO2C6H4, R1=NO2, R2=H; b R=3-NO2C6H4, R1=NO2, R2=CH3; c R=4-CH3OC6H4, R1=NO2, R2=H; d R=4-CH3OC6H4, R1=NO2, R2=CH3; e R=4-CH3OC6H4, R1=CO2Et, R2=H; f R=4-CH3OC6H4, R1=CO2Et, R2=CH3; g R=4-CH3C6H4, R1=CO2Et, R2=H.

EFFECT: preparation of the compound exhibiting antileprous and antituberculous activity.

1 cl, 1 tbl, 1 ex

FIELD: medicine.

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

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

4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I)

or pharmaceutically acceptable salts thereof, in which: R1, R2, R3, R4, A and E are as described in the claim, and to pharmaceutical composition containing said compounds, and a method of treating and application in order to treat conditions mediated by antagonistic activity towards acid pump, such as gastrointestinal diseases, gastrooesophageal diseases, gastrooesophageal reflux disease (GERD), laryngopharyngeal reflux disease, peptic ulcers, gastric ulcers, duodenal ulcers, NSAID- induced ulcers, gastritis, Helicobacter pylori infection, dyspepsia, functional dyspepsia, Zollinger-Ellison syndrome, nonerosive reflux disease (NERD), viscerogenic pain, cancer, heartburn, nausea, oesophagitis, dysphagia, hypersalivation, disorders of the respiratory channel or asthma.

EFFECT: possibility of using compounds to treat different diseases.

9 cl, 1 tbl, 16 ex

FIELD: medicine.

SUBSTANCE: after 6-day extraction of cultivated licorice with 40% ethanol, buffer, which contains wt % calcium chloride not more than 0.014, potassium chloride not more than 0.04, monosubstituted potassium phosphate not more than 0.006, magnesium sulphate not more than 0.02, magnesium chloride not more than 0.02, sodium chloride not more than 0.08, sodium acid carbonate not more than 0.035, sodium phosphate disubstituted not more than 0.024; glucose not more than 0.1, dissolved in 100 ml of distilled water, is added into unfiltered mixture (20 g of vegetable raw material in 100 ml of alcohol solution) in ratio 1:1 (100 ml of mixture, 100 of buffer), obtained solution is kept at temperature 3°C in dark place for the following 4 days with its daily shaking. After that, solution is filtered and autoclaved three times at 0.5 atm for 10 min.

EFFECT: invention allows to realise said purpose.

9 tbl, 3 ex

FIELD: organic chemistry, antibacterial agents.

SUBSTANCE: invention relates to an agent used against acid-resistant microorganisms containing derivative of pyridone carboxylic acid as an active component, its pharmaceutically acceptable salt or its hydrate that elicits high antibacterial activity against Mycobacterium tuberculosis and atypical acid-resistant microorganisms. Invention describes agent used against acid-resistant microorganisms containing compound represented by the following formula (I) its salt or its hydrate as an active component wherein R1 represents cyclic alkyl group comprising 3-6 carbon atoms that can comprise substitute(s) chosen from halogen atom; R2 represents hydrogen atom; R3 represents hydrogen atom; A1 represents incomplete structure represented by the formula (2): wherein X2 represents halogen atom, alkyl group comprising 1-6 carbon atoms or alkoxy-group comprising 1-6 carbon atoms; A1, A2 and A3 form incomplete structure of the formula: in common with carbon atoms combined with them; X1 represents halogen atom; Y represents hydrogen atom; Z represents phenylpiperazine substitute. Invention provides synthesis of pyridone carboxylic acid eliciting high antibacterial activity against Mycobacterium tuberculosis and atypical acid-resistant microorganisms in combination with good pharmacokinetics indices and safety.

EFFECT: valuable biological property of agent.

10 cl, 9 tbl, 10 ex

FIELD: chemistry of heterocyclic compounds, antibacterial agents.

SUBSTANCE: invention relates to agent used against acid-resistant microorganisms. Invention describes agent against acid-resistant microorganisms containing as an active component the compound represented by the general formula (1) or its hydrate wherein R2 represents hydrogen atom; R3 represents hydrogen atom; A1, A2 and A3 form incomplete structure of the formula: wherein A1 represent incomplete structure of the formula: wherein X2 and above described R1 can be combined to form six-membered cyclic structure comprising part of the parent nucleus wherein formed ring can comprise oxygen atom and, except for, can comprise alkyl group having 1-6 carbon atoms as a substitute; X1 represents halogen atom, hydrogen atom or amino-group; Y represents hydrogen atom; Z represents incomplete structure of the formula: . Agent elicits high antibacterial activity of broad spectrum and possesses good pharmacokinetics and safety also.

EFFECT: improved and valuable properties of agent.

3 cl, 9 tbl, 10 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to 4,4'-sulfonyl-bis-(N,N'-dimethylammoniomethyleneaniline)-chloride, 6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonate of the formula (I) eliciting antibacterial, antimycobacterial and immunotropic activities. Also, invention describes a pharmaceutical composition based on compound of the formula (I).

EFFECT: valuable medicinal properties of compounds and composition.

3 cl, 7 tbl, 2 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new 6-alkyl-5-(2-isonicotinoylsulfohydrazoyl)uracil hydrochlorides of the general formula (I) wherein R means alkyl comprising 1-4 carbon atom. Compounds possess an anti-mycobacterial and an immunotropic activity and can be used as an immunomodulating agent and an anti-mycobacterial agents. Also, invention relates to a pharmaceutical composition based on thereof.

EFFECT: valuable medicinal properties of compounds.

4 cl, 10 tbl, 2 ex

The invention relates to the field of medicine and for new dosage forms of demoliton

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to biotechnology, virology and medicine. What is disclosed is a recombinant protein containing one or more polypeptides carrying one or more epitopes of one or more human papilloma virus HPV antigens. Said polypeptides are embedded in one or various permissive sites of adenylatecyclase (CyaA) or its fragments. What is also disclosed is the polypeptide coding such protein and their use in expression systems for producing immunogenic compositions and drugs. The invention can be used in medicine.

EFFECT: CyaA fragment possesses the property of said adenylatecyclase protein for targeted interaction with antigen-presenting cells.

60 cl, 21 dwg, 1 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a mixture of diastereomeric compounds where C* denotes a mixture of R- and S-isomers; and the R-isomer constitutes over 50% of the mixture with respect to the S-isomer in the C* position.

EFFECT: obtained mixture is effective for inhibiting serine protease.

16 cl, 8 tbl, 6 dwg, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to 5'-aminocarbonylphosphonate 3'-azido-3'-deoxythimidine salts showing anti-HIV-1 activity of general formula

where R is an alkaline and alkaline earth metal ion, or an ammonium ion with various substitutes.

EFFECT: preparing new compounds showing the ability to inhibit the human immunodeficiency virus selectively and being stable substances that facilitates preparing based drugs.

1 cl, 12 ex, 1 tbl

Antiviral compound // 2441010

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds or their pharmaceutically acceptable salts where the compound has formula (I). The compounds have the properties of hepatitis C virus (HCV) replication inhibition and can be used for treating HCV-infection. In formula (I) B represents heterocyclyl selected from thieno, thiazolo, pyrazolo, pyrido and pyrimidogroup with B being optionally substituted by one or more R18, A represents phenyl which is optionally substituted by one or more R18; each W1 and W2 are independently selected from N or C(R33); Z represents -NH-; each R10 and R33 containing of hydrogen; X is selected from a group consisting of -Ls-O-, -Ls-S-; R22 means hydrogen or phenyl optionally substituted by one or more R26 ; Y is selected from a group consisting of -Ls-O-, -Ls-S-; -Ls-C(O)- and -Ls-NH(SO)2-; R50 represents -L1-A1, where L1 represents a bond, and A1 is selected from a group consisting of carbocyclyl where carbocyclyl represents phenyl or C3-C6carbocyclyl, banzimidazolyl and C1-C6alkyl optionally substituted by phenyl where A1 is optionally substituted by one or more R30 ; the substitute values are specified in the patent claim.

EFFECT: preparing the compounds exhibiting the properties of hepatitis C virus replication inhibition.

17 cl, 8 dwg, 255 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel methyl, chloro and nitro-derivatives of N-{3,5-dioxo-4-azatetracyclo [5.3.2.02,6.08,10]dodec-11-en-4-yl}-2-hydroxybenzamide of formula I:

la R=5-Cl, lb R=4-Me, Ic R=5-Me, Id R=5-NO2, which exhibit antiviral activity with respect to different types of orthopoxviruses which are pathogenic for humans and animals. The compounds are obtained through reaction of hydrazides of derivatives of ortho-hydroxybenzoic acid with 4,4a,5,5a,6,6a-hexahydro-4,6-etheno-1H-cycloprop/f/isobenzofuran-1,3(3aH)-dione in acetic acid while boiling for 8-12 hours. Output is equal to 91-98%.

EFFECT: obtaining novel compounds.

1 dwg, 2 tbl, 6 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to phthisiology, pulmonology, thoracic surgery. Method includes standard anti-tuberculosis treatment. Into pleural cavity, without extraction of pleural fluid introduced is mixture of medications, consisting of 10 thousand units of contrical, 5 thousand units of heparin and 30 mg of prednisolone at the background of standard antibacterial treatment. Introduction of medication mixture is carried out on 5-6 ml of pleural fluid. If treatment of pleurisy is started in due time, mixture is introduced single time, in case of total, chronic or recurring pleurisy mixture is introduced 2-3 times with 7-10 day intervals.

EFFECT: method ensures reduction of disease treatment terms, due to efficient elimination of inflammation and prevention of immunodeficient state caused by loss of protein substances, contained in pleural fluid, is economical and non-burdensome either for patient or for physician.

2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of virology. Vaccine contains culture liquid of attenuated strain "IS" of epizootic swine diarrhea virus with titre 4.7-5.5 lg "ТЦД"50 and drying medium with ratio 7:3. Vaccine is introduced to sows twice on 75-80 and 90-95 days of gestation in dose 104 "ТЦД"50 for prevention of epizootic swine diarrhea.

EFFECT: vaccine is safe, areactogenic, possesses expressed protective properties.

2 cl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions relates to medicine, namely to virology, hepatology, and can be used for treatment or prevention of viral hepatitis C infection. For this purpose therapeutically efficient amount of 3-[(R)-2-(N,N-dimethylamino)ethylthio-Sar]-4-(gamma-hydroxymethylleucin) cyclosporine or its pharmaceutically acceptable salt or solvate in combination with therapeutically efficient amount of second preparation is introduced to patient. Second preparation is selected from modulators of protease NS3-4A, nucleoside modulators RNA-dependent RNA-polymerase NS5B, non-nucleoside modulators RNA-dependent RNA-polymerase NS5B, riboflavin and immunomodulating medications. Also claimed are pharmaceutical compositions and sets.

EFFECT: introduction of claimed combinations of medications makes it possible to achieve high virologic response.

17 cl, 1 tbl, 8 ex, 3 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to creation of composition for oral cavity care, which have, at least, two vegetable active ingredients, obtained from plants. Composition for oral cavity care also includes per oral acceptable carrier for introduction of sufficient amount of, at least, two active ingredients in vivo.

EFFECT: vegetable active ingredients ensure to compositions for oral cavity especially efficient antimicrobial (antibacterial, antiviral and/or antifungal antioxidant anti-inflammatory ageing slowing down and/or healing properties.

5 cl

FIELD: chemistry.

SUBSTANCE: invention describes novel polynucleotide and amino acid sequences of Brachyspira hyodysenteriae, which can be used to diagnose diseases in animals, caused by B. hyodysenteriae, to treat or prevent diseases associated with infection with B. hyodysenteriae. The invention describes a cell containing a plasmid containing a polynucleotide, for treating and preventing a disease associated with infection of an animal with B. Hyodysenteriae. The invention describes immunogenic and vaccine compositions for generating immune response in an animal, which contain a polypeptide, a polynucleotide, a cell or a plasmid for treating or preventing infection of animals by B. hyodysenteriae, as well as sets of instruments for diagnosis which contain a monoclonal antibody, capable of biding the disclosed polypeptide or a polypeptide or polynucleotide. The invention enables to successfully diagnose diseases caused by B. hyodysenteriae, prevent or treat animals infected with B. hyodysenteriae. The sequences described herein can be used for diagnosis and therapeutic and/or preventive treatment of animals from diseases caused by other types of Brachyspira, including B. intermedia, B. suantatina, B. alvinipulli, B. aalborgi, B. innocens, B. murdochii and B. pilosicoli.

EFFECT: high efficiency of using the composition.

39 cl, 4 tbl

FIELD: food industry.

SUBSTANCE: invention relates to a non-allergenic food product. The food product includes an amino acid fraction containing at least one component chosen from the group consisting of amino acids and peptides with a degree of polymerisation 7 or less, and a lipid fraction containing at least one fatty acid chosen from the group consisting of arachidonic acid and docosahexanoic acid. The composition content of protein and other peptides with molecular weight 1000 daltons or more (in relation to dry weight) is less than 0.01 wt %, preferably - no less than 0.001 wt %, more preferably - no less than 0.0001 wt %. The food product is used for allergy diagnostics.

EFFECT: invention allows to produce a product which does not impart allergic reactions and is able to attenuate intensity of the patients' allergic reactions.

7 cl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical industry, in particular to method of suppressing increase of glucose level in blood with glucose load, reduction of glucose blood level, improvement of insulin-resistance. Method of suppressing glucose level in blood under glucose loading, reduction of glucose blood level, improvement of patient's insulin-resistance, including introduction to patient of efficient quantity of composition, which contains oligosaccharides in defined concentration, where oligosaccharides are β-1,4-manooligosaccharides with degree of polymerisation 2-10.

EFFECT: method described above efficiently suppresses increasing of glucose blood level under glucose loading, reduces blood glucose level, improves insulin-resistance of patient.

6 cl, 2 dwg, 2 tbl, 4 ex

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