Lactoferrin and neuronal health and developing intestine in infants

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to neuronal health, neuronal protection and neuronal development, and refers to using a composition containing lactoferrin in the concentration of at least 0.1 g/100 kcal of the composition for treating or preventing diseases related to retarded enteral nervous system and/or disturbed enteral nervous system. The composition is specified in a group consisting of food products, products for animals, pharmaceutical compositions, nutrient formulations, nutrieceuticals, drinks, biologically active food additives, baby's formulas. The composition can additionally contain a protein source, a lipid source and a carbon source. The composition is administered into pregnant women, nursing mothers, premature and mature newborn children, infants, toddlers, children and/or adolescents.

EFFECT: preparing the composition for neuronal protection.

14 cl, 1 ex, 4 dwg

 

The present invention relates to the field of neuronal health, neuronal protection and neuronal development. One embodiment of the present invention relates to compositions that can be used to treat or prevent delayed development of the enteric nervous system. Neuronal cells in the intestine can be protected. Their development/growth can be stimulated, for example, if neuronal delay should be restored. Disorders associated with delayed development of the enteric nervous system and/or with a damaged nervous system can be treated or prevented by the introduction contains lactoferrin compositions in accordance with the present invention.

The nervous system is a highly complex network of neurons and glial cells. It is present in all species of mammals. The nervous system consists of Central nervous system (brain and spinal cord) and peripheral nervous system (somatic, autonomic and enteric nervous system). Central nervous system controls cognitive functions (memory, attention, perception, activities, etc.)

Central nervous system controls cognitive functions (memory, attention, perception, activities, etc.). Together with the peripheral nervous system it plays a fundamental role monitoring of behavior. The somatic nervous system is responsible for coordinating movements of the body (under the control of consciousness). The autonomic nervous system maintains homeostasis activity of the body without mind control (heart beat rate, etc.). Finally, as the last part, the enteric nervous system that directly controls the gastrointestinal tract, such as intestinal barrier, motility, absorption, digestion and secretion, and participates thus in the protection of the intestine from any impacts and provides digestive comfort.

The nervous system develops during pregnancy and then in the postnatal period improved to a Mature functional state.

Immaturity or delay in maturation of the nervous system leads to the delayed formation of important biological functions it regulates. In particular, it leads to dysfunction of the intestine after birth, including low digestive/absorption capacity, gastrointestinal reflux, slow passage of bowel, a weakened intestinal barrier function, leading to food intolerances (respectively, to the necessity of parenteral nutrition support), discomfort in the intestines, accompanied with hard stools and increased risk of infection and Allergy.

The present invention was Ulu�stitching the state of the prior art and to provide an arrangement, based on natural ingredients, which help to maintain the development of the nervous system of the intestine and to protect her.

This problem is solved by the totality of essential features presented in the independent claims.

The authors of the present invention were able to show that lactoferrin, for example a composition comprising lactoferrin, can be used to support the development of neuronal cells and to protect them.

It was further shown that the introduction lactoferrin can increase the density of neurons and their survival.

Lactoferrin (LF), also known as lactotransferrin (LTF), is a globular multifunctional protein that you know is that it has antimicrobial activity and is part of the innate system of protection, primarily protecting the mucous membranes.

Lactoferrin can be found, for example, in milk and serum, and in many of the secretions of the mucous membranes, such as tears and saliva. Therefore, lactoferrin can be isolated, for example, from milk or you can get recombinant his way.

The present invention relates to lactoferrin, derived from any source.

For example, lactoferrin from milk or saliva has the advantage that it is a natural ingredient derived from mixtures of substances for food purity, and therefore it can be used as� in the form of enriched fractions of food composition without further purification.

The obtained recombinant lactoferrin way has the advantage that it can be easily obtained in high concentrations.

Colostrum contains relatively high concentration of lactoferrin, followed by human breast milk and cow's milk.

The authors present invention found that the lactoferrin or enriched with lactoferrin composition can be used to protect neuronal cells from degeneration. This degeneration can occur, for example, after stressful situations, such as acting on the fetus (vnutrimatocny) or newborn (hypoxia-ischemia at birth, oxygen therapy and hyperoxia, inflammation, need for parenteral support, etc.). It was shown that lactoferrin promotes the survival of neuronal cells and/or limits or prevents neuronal death of enteric neuronal cells and stimulates neuronal growth, which plays an important role, for example, in the development process.

In young children lactoferrin and/or containing lactoferrin composition of the present invention can be used to protect the enteric nervous system from any stress, for example, occurring during the period of neuronal development, and, consequently, to restrict and/or prevent stress induced growth retardation and is associated�'s with her bowel dysfunction.

In the context of the present invention, the term "children" includes infants and persons aged 0 to 14 years.

Infants aged less than 1 month are called newborns.

The term "newborn" includes premature infants, postmature children and full-term newborns. Under one year of age or begun to walk young children called toddlers or children who are able to walk (usually 12-36 months).

Lactoferrin and/or composition of the present invention can be entered, for example:

- infants

- newborn,

mothers during pregnancy and/or lactation,

- premature or full-term children with intrauterine growth retardation, which may occur as a result of any adverse processes during pregnancy (e.g., Smoking mother, his mother is taking drugs, poor quality of the placenta, abnormal location of the placenta, malnutrition of the mother or fetus, etc.)

- premature infants without fetal intrauterine growth,

- children with low/very low birth weight,

- when inorganic disorders successful development of children,

- any infants and children with growth retardation nervous system through, for example, hypoxemia-ischemia at birth or any other adverse processes and/or Liu�th infants and children with gastrointestinal dysfunction (impaired digestion, motor disorders, gastrointestinal reflux, slow passage of bowel intolerance of oral intake), with Hirschsprung's disease and inflammation affecting the gastrointestinal tract, such as necrotizing enterocolitis), with pathologies associated with obstruction.

Lactoferrin and/or composition of the present invention can be entered, thus, children and/or mothers during pregnancy and/or lactation.

Therefore, one embodiment of the present invention is a composition enriched with lactoferrin, for oral administration.

Enriched means that either lactoferrin added to the composition so that the resulting content in the composition is greater than the concentration of lactoferrin in the composition without the addition of lactoferrin, or that the composition is processed in such a way as to concentrate the natural content of lactoferrin in the composition.

Lactoferrin can be used as a pure compound.

In another embodiment, the lactoferrin may be used as enriched lactoferrin fraction, for example enriched with lactoferrin fraction of milk or whey.

As a source of milk or whey can be used, for example, cow's milk, human breast milk, goat's milk, camel's milk, Mare's milk and milk of a donkey. Can �be also used colostrum.

For therapeutic purposes the composition is administered in amounts sufficient to, at least, to cure or stop the symptoms of violations and/or its complications. Satisfy this condition number is defined as "therapeutically effective dose". Amounts effective for this purpose will depend on a number of factors known in the art, such as the severity of the violation, the weight and General condition of patient. In the preventive purposes of the composition of the present invention is administered to a patient, a part of the group at risk or subject to a violation in an amount sufficient to at least reduce the risk of violations. This amount is defined as a "prophylactically effective dose". In this case, the exact number also depends on the number of specific patient factors such as health status and weight of the patient.

Lactoferrin can be entered into the scheme of the present invention in a therapeutically effective dose and/or prophylactically effective dose.

Typical enriched with lactoferrin composition may contain lactoferrin in the amount of at least 1.6 g/L.

For example, the composition of the present invention may contain lactoferrin in a concentration of at least 0.75 mass%, preferably at least 1 mass%.

In one embodiment �oppoziciu should be entered in the quantity corresponding to the reception of at least 0.25 g of lactoferrin, preferably at least 0.5 g of lactoferrin, most preferably at least 1 g of lactoferrin per day per kg of body weight.

For example, pregnant and/or lactating mothers, it is possible to adopt a composition in an amount corresponding to at least 1 g of lactoferrin/kg of body weight per day.

Children can take the composition in an amount corresponding to at least 200 mg lactoferrin/kg of body weight per day.

Lactoferrin may be present in the composition in a concentration of at least 0.01 g per 100 kcal, preferably at least 0.1 g per 100 kcal. For example, lactoferrin can be present in the composition in the range of approximately 0.01 g - 100 g, preferably 0.01 g to 50 g, more preferably 2 g to 25 g per 100 kcal of the composition.

Lactoferrin can also be used in combination with other compounds, such as sialic acid and/or iron.

Sialic acid is a generic name N - or O-substituted derivatives Narimanovo acid, a monosaccharide with deleteoperation skeleton.

Any of sialic acid can be used for the purposes of the present invention. However, preferably it has the following formula:

R1=H, acetyl, lactel, methyl, sulfate, phosphate, angidro, sialic acid, fucose, glucose or galactose;

R2=N-acetyl, N-glycolyl, amino, hydroxyl, N-glycolyl-O-acetyl or N-glycolyl-O-methyl;

R3=H, galactose, N-acetylglucosamine, sialic acid, N-glycolylneuraminic acid.

R1 may be selected from the group consisting of H, acetyl, Lactina, bromide, sulfate, phosphate, unheroically acid, fucose, glucose and/or galactose.

R2 may be selected from the group consisting of N-acetyl, N-glycolyl, amino, hydroxyl, N-glycolyl-O-acetyl and/or N-glycolyl-O-methyl.

R3 may be selected from the group consisting of N, galactose, N-acetylglucosamine, sialic acid and/or N-glycolylneuraminic acid.

Group in position R1 may be identical or may differ from each other.

For example, sialic acid can be N-acetylneuraminic acid with R1=H, R2=N-acetyl and R3=N. In accordance with further embodiments of the present invention, sialic acid can be selected from the group consisting of 2-keto-5-atsetamido-3,5-dideoxy-d-glycero-d-galactouronic acid (Neu5Ac) and 2-keto-3-deoxy-d-glycero-d-galactono acid (KDN) or their mixtures.

Sialic acid used in the present invention contains N-acetylneuraminic acid, which has the following synonyms and abbreviations: o-Sialic acid; 5-atsetamido-3,5-dideoxy-D-glycero-D-galactosemia acid; 5-atsetamido-,5-dideoxy-D-glycero-D-galactosemia acid; Atsinanana acid; N-Acetyl-neuraminic; N-Acetyl-karamanova acid; NANA and Neu5Ac.

The most preferred lactoferrin-containing composition comprises sialic acid in an amount in the range from 100 mg/100 g (by weight) to 1000 mg/100 g (by weight) of the composition, for example in the range from 500 mg/100 g (by weight) to 650 mg/100 g (by weight) of the composition.

The composition of the present invention may, for example, contain at least about 0.001 wt.% sialic acids. In further embodiments of the present invention, the composition may contain at least about 0.005 wt.% or at least about 0.01 wt.% sialic acids.

In another embodiment, one or more lactoferrin-containing composition may contain iron in an amount in the range of from about 1 mg/100 g (by weight) to 100 mg/100 g of the composition, for example 10 mg/100 g (by weight) to 30 mg/100 g of composition.

One lactoferrin-containing composition may contain, for example, approximately 852 mg/100 g (by weight) of sialic acid and 22 mg/100 g (by weight) of iron.

Lactoferrin-containing composition of the present invention may have a caloric/energy value in the range of 30 kcal/100 g to 1000 kcal/100 g of composition, preferably from 50 kcal/100 g to 450 kcal/100 g of composition. It may, for example, have Kalo�inost approximately 400 kcal/100 g.

Type of composition privately is not limited. It is preferably a composition for oral or enteral administration.

The composition may, for example, be selected from the group consisting of food products, products for animals, pharmaceutical compositions, nutritional formulations, nutraceuticals, drinks, food supplements and infant formula.

In one typical embodiment of the present invention, the composition comprises a protein source, a source of lipids and a source of carbohydrates.

The composition contains a protein source that may be present in the range between 1.4 and 100 g/100 kcal, preferably between 2 and 6.0 g/100 kcal of the composition. Since lactoferrin is a protein, it should be considered part of the protein source.

The type of protein is not considered critical to the present invention. For example, you can use the protein sources based on whey, casein, or their mixtures. As for whey protein, you can use acid whey, sweet whey or mixtures thereof, as well as alpha-lactalbumin and beta-lactalbumin in any desired proportion. Whey protein can be modified whey. Sweet whey is a readily available by-product of cheese production and is often used�ized in the production of infant formula based on cow's milk. However, sweet whey includes a feature called caseino-Glyco-macropeptide (CGMP), which is rich in threonine and poor in tryptophan, which is undesirable. Removing CGMP from sweet whey makes the content of threonine closer to breast milk. This modified sweet whey can then be supplemented with those amino acids, the contents of which are small (mainly histidine and tryptophan). The process of removing CGMP from sweet whey is described in EP 880902, and children nutrient mixture on the basis of such a modified sweet whey is described in WO 01/11990. Proteins can be intact or hydrolyzed herbal fibers, or be a mixture of intact and hydrolyzed proteins. It may be desirable to use a partially hydrolysed proteins (degree of hydrolysis between 2 and 20%), for example, for persons who have a suspected risk of developing allergies to cow's milk. If you require hydrolysed proteins, the hydrolysis can be performed at will and according to the known technique. For example, hydrolyzed whey protein may be prepared by enzymatic hydrolysis of whey fraction in two stages, as described in EP 322589. To obtain intensely hydrolyzed protein whey proteins may be subjected to triple hydrolysis using Alcalase 2.4 L (EC 940459),�eat Neutrase 0.5 L (obtainable from Novo Nordisk Ferment AG), and then Pancreatin at 55°C. If the whey fraction used as the starting material, contains almost no lactose, it is shown that in the process of protein hydrolysis is significantly lower, and the blocking of lysine. This reduces the blocking of lysine in approximately 15% of the total weight of lysine to less than about 10% by weight of lysine; for example about 7% by weight of lysine, which greatly improves the nutritional value of a protein source.

It is known that whey proteins provide a number of benefits for health. The protein fraction in whey (approximately 10% of the total weight of solids of the whey) contains several protein fractions, such as beta-lactoglobulin, alpha-lactalbumin, bovine serum albumin and immunoglobulins. In one embodiment at least 50%, preferably at least 75%, even more preferably at least 85% by weight of the protein source is whey protein.

The compositions of the present invention may contain a source of lipids. The source of the lipid can be any lipid or fat. Preferred sources of fat include milk fat, palm olein, sunflower oil with high content oleinu. Can also be added essential fatty acids Lineva acid and alpha-linolenic �Isleta, and also by small amounts of oils containing many converted arachidonic acid and docosahexaenoic acids, such as oils from fish or from microorganisms. The source of lipids is preferably the ratio of fatty acids n-6 to n-3 is equal to from about 5:1 to about 15:1; for example from about 8:1 to about 10:1.

In the presence of a source of lipids it may be responsible for 30-50% of the total energy value of the composition.

The compositions of the present invention may contain a source of carbohydrates. Can be used any source of carbohydrates, such as lactose, saccharose, maltodextrin, starch and mixtures thereof.

The source of carbohydrates may be responsible for 35-65% of the total energy value of the composition.

For example, the composition of the present invention may contain protein in the range from about 1.8 to 3.0 g/100 kcal, lipids from about 4.4 to 6.5 g/100 kcal and/or carbohydrates from approximately 60 to 75 g/100 kcal.

The compositions of the present invention may also contain all vitamins and minerals, for which it is established that their presence in quantities that are significant for the power needed in a daily diet. Minimum requirements have been established for certain vitamins and minerals. Examples of minerals, vitamins and other nutrients, not necessarily in�westwoodi in children's nutrient mixtures, include vitamin a, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin E, vitamin K, vitamin C, vitamin D, folic acid, Inositol, Niacin, Biotin, Pantothenic acid, choline, calcium, phosphorus, iodine, iron, magnesium, copper, zinc, magnesium, chloride, potassium, sodium, selenium, chromium, molybdenum, taurine and L-carnitine. Minerals are usually added in the form of salts. The presence and amount of specific minerals and other vitamins varies depending on many factors, such as age, weight and condition of a person or animal who administered the composition.

The composition may also contain at least one probiotic bacterial strain. Probiotic is a preparation of microbial cells or components of microbial cells that have a positive impact on the health or wellbeing of the host. Suitable probiotic bacterial strains include Lactobacillus rhamnosus ATCC 53103 obtainable from Valio Oy of Finland under the trademark LGG, Lactobacillus rhamnosus CGMCC 1.3724, Lactobacillus paracasei CNCM 1-2116, Lactobacillus reuteri ATCC 55730 and Lactobacillus reuteri DSM 17938 obtainable from BioGaia AB, Bifidobacterium lactis CNCM 1-3446 sold inter alia by the Christian Hansen company of Denmark under the trade mark YOU 2 and Bifidobacterium longum ATCC BAA-999 sold by Morinaga Milk Industry Co. Ltd. Japan, under the trademark VV. The amount of a probiotic, if present, is also preferably varies as a function of age �of a person or animal. Generally speaking, the contents of a probiotic can increase with the age of the child from 103up to 1012CFU/g mixtures, more preferably 104-108CFU/g mixtures (based on dry weight).

The composition may also contain at least one prebiotic in an amount of from 0.3 to 10%. A prebiotic is nevereverever food component has a positive effect on the host, selectively stimulating the growth and/or activity of one or limited number of bacteria in the colon, and thus improves the health of the host. Such ingredients are not digested in the sense that they do not disintegrate and are absorbed in the stomach or small intestine and thus pass intact to the colon where they are selectively fermented by beneficial bacteria. Examples of prebiotics include certain oligosaccharides, such as fructooligosaccharides (FOS) and galactooligosaccharides (GOS). Can be used a combination of prebiotics, such as 90% GOS with 10% short chain fruit-oligosaccharides such as the product sold under the trade mark Raftilose® or 10% inulin such as the product sold under the trademark Raftiline®.

The preferred prebiotic is a mixture of galactooligosaccharide(s), N-acetylated(e) oligosaccharide(s) and solirovanie(e) oligosaccharide(s) in which the N-acetylated(e) oligos�reed(s) contains from 0.5 to 4.0% of a mixture of oligosaccharides, galactooligosaccharide(s) contains from of 92.0 to 98.5% of a mixture of oligosaccharides and solirovanie(e) oligosaccharide(s) contains from 1.0 to 4% of a mixture of oligosaccharides. This mixture is further referred to as "CMOS-GOS". Preferably the composition for use according to the invention contains from 2.5 to 15 wt.% CMOS-GOS by weight with the clarification that the composition comprises at least 0.02 wt.% N-of acetylated oligosaccharide, at least 2 wt.% galactooligosaccharide and at least 0.04 wt.% sieciowego of oligosaccharide.

Suitable N-acetylated oligosaccharide includes GalNAcα1,3Galβ1,4Glc and Galβ1,6GalNAcα1,3Galβ1,4Glc. N-acetylated oligosaccharides can be prepared by the action of glucosaminidase and/or galactosaminidase N-acetylglycine and/or N-acetylacetone. For this purpose, can also be used N-acetylgalactosamine transferase and/or N-acetylglycine transferase. N-acetylated oligosaccharides can also be formed by the technique of fermentation with the appropriate enzymes (recombinant or natural) and/or microbial fermenting. In the latter case microbes may either Express their natural enzymes and substrates, or may be formed so as to make the respective substrates and enzymes. Can be used odnomikronnoye culture or mixture of cultures. The formation of N-acetyl�separate oligosaccharide can be initiated by acceptor substrates, starting with any degree of polymerization (DP) from DP=1 and next. Another option is the chemical transformation of ketohexose (e.g., fructose), loose or related oligosaccharide (e.g. lactulose) in N-acetylgalactosamine or N-acetylhexosamines containing oligosaccharide, as described in Wrodnigg, T. M.; Stutz, A. E. (1999) Angew. Chem. Int. Ed. 38:827-828. Suitable galactooligosaccharides include Galβ1,6Gal, Galβ1,6Galβ1,4Glc Galβ1,6Galβ1,6Glc, Galβ1,3Galβ1,3Glc, Galβ1,3Galβ1,4Glc, Galβ1,6Galβ1,6Galβ1,4Glc, Galβ1,6Galβ1,3Galβ1,4Glc Galβ1,3Galβ1,6Galβ1,4Glc, Galβ1,3Galβ1,3Galβ1,4Glc, Galβ1,4Galβ1,4Glc and Galβ1,4Galβ1,4Galβ1,4Glc. Synthetic galacto-oligosaccharides, such as Galβ1,6Galβ1,4Glc Galβ1,6Galβ1,6Glc, Galβ1,3Galβ1,4Glc, Galβ1,6Galβ1,6Galβ1,4Glc, Galβ1,6Galβ1,3Galβ1,4Glc and Galβ1,3Galβ1,6Galβ1,4Glc, Galβ1,4Galβ1,4Glc and Galβ1,4Galβ1,4Galβ1,4Glc and mixtures thereof are commercially available under the trade marks Vivinal ® and Elix''or ®. Other suppliers of oligosaccharides is Dextra Laboratories, Sigma-Aldrich Chemie GmbH and Kyowa Hakko Kogyo Co., Ltd. In another embodiment, for the production of neutral oligosaccharides can be used by specific glycosyltransferases, such as galactosyltransferase.

Suitable Valerevna oligosaccharides include NeuAcα2,3Galβ1,4Glc and NeuAcα2,6Galβ1,4Glc. These Valerevna oligosaccharides can be separated by chromatographic or filtration technology from natural sources such as milk animals. In another embodiment, they can also be obtained by means of biotechnology using specification�tion seatransport either using the technique of fermentation, based on the enzymes (recombinant or natural enzymes), or using the technique of microbial fermentation. In the latter case, the microbes may either Express their natural enzymes and substrates, or may be formed so as to make the respective substrates and enzymes. Can be used for the culture of a single strain or a mixture of crops. Education sialyl-oligosaccharide can be initiated by acceptor substrates starting from any degree of polymerization (DP) from DP=1&" >

The compositions may optionally contain other compounds that may have positive effects, such as nucleotides, nucleosides, and the like.

For use according to the invention compositions, such as baby formula, can be prepared by any suitable method. For example, you can prepare baby formula, mixing in appropriate proportions protein source, a carbohydrate source and a fat source. Optionally, the mixture can include emulsifiers. At this stage you can add the vitamins and minerals that are usually added later to avoid thermal degradation. All of lipophilic vitamins, emulsifiers, etc. before mixing can be dissolved in fat. Then, the liquid mixture can be added to water, preferably water, under�ergota reverse osmosis. Then, the liquid mixture may be subjected to heat treatment to reduce bacterial contamination. For example, the liquid mixture may be rapidly heated to a temperature in the range of from approximately 80°to approximately 110°C for from about 5 seconds to about 5 minutes. This can be accomplished by steam injection or by heat exchanger; for example a plate heat exchanger. Then, the liquid mixture can be cooled to from about 60°to about 85°C; for example, pulsed cooling. The liquid mixture may then be homogenized; for example in two stages from about 7 MPa to about 40 MPa in the first stage and about 2 MPa to about 14 MPa in the second stage. Then homogenisierung the mixture may be further cooled to add any temperature-sensitive components; such as vitamins and minerals. The pH and the solids content of the homogenized mixture is convenient to standardize at this point. Homogenized mixture is transferred to a suitable drying apparatus such as a spray drier or freeze drier and converted to powder. This powder should contain not more than 5% by weight of moisture. If you want to add a probiotic(s), they should be cultured in any suitable manner and �podgotovitj to adding to child nutrition, for example, by freeze drying or spray drying. Alternatively, bacterial preparations can be bought from specialist suppliers such as Christian Hansen and Morinaga, already prepared in a suitable form for adding to children's nutrient mixture. Such bacterial preparations can be added to powdered infant mixture by dry mixing.

Lactoferrin can be added at any stage of this procedure, but preferably after the heating stage.

The present invention expands the use of lactoferrin for preparing a composition for the treatment or prevention of a delay in the development of the enteric nervous system and/or preventing gastrointestinal disorders associated with a delay in the development of the enteric nervous system and/or damaged enteric nervous system.

Lactoferrin or a composition according to the present invention can also be used to repair damaged enteric nervous system.

Disorders associated with a delay in the development of the enteric nervous system, and/or impaired enteric nervous system include, for example, reduced digestive or adsorption capacity, gastrointestinal reflux, slow the rate of passage of the intestine, a weakened intestinal barrier function, the neper�nosimost enteral nutrition, discomfort in the intestines, solid chair.

In another embodiment of the present invention, the composition comprising Lactoferrin, can be used to treat or prevent delayed neuronal migration.

The composition of the present invention can be used to enhance neuronal density and/or neuronal survival.

For the purposes of this invention it is essential that the composition contain lactoferrin or a connection that turns into lactoferrin after administration. The composition should not be enriched with lactoferrin, although this may be preferred, since in this case a greater amount of lactoferrin can be injected in smaller volumes.

Lactoferrin can be used for the preparation of any of the compositions. However, preferably, the lactoferrin was received in the form of a composition corresponding to that described above.

To achieve this, the composition can be administered to mothers during pregnancy, mothers during lactation, premature or full-term infants, children with intrauterine growth retardation, infants, children and adolescents.

Experts will understand that it is easy to combine all of the features of the present invention, without departing from the claims of the invention described. In particular, features described for the use of this invented�I, can be attributed to the composition of the present invention and/or lactoferrin and Vice versa.

Further advantages and features of the present invention are set forth in the following examples and figures.

Figure 1 shows the percentage of positive NS20Y cells for narango process (the main process of the neuron) in the initial conditions (untreated cells) and after treatment of cells or neurotrophin factor CNTF (100 ng/ml, positive control) or enriched with lactoferrin fraction of cow's milk at different concentrations. Data are presented as mean ± SEM, n=3 to 7, depending on the group (Baseline, n=7; CNTF, n=3; 1 µg/l, n=3; 10 µg/l, n=7; 100 µg/l, n=3; 1 mg/l, n=3; 10 mg/l, n=5; 100 mg/l, n=7; 1 g/l, n=6). Data were compared with the original untreated group using student's t-test. A difference was considered significant if P<0,05.

Figure 2 shows the release of neuron-specific enolase ((NSE), a marker of neuronal death in primary cultures of enteral neurons under the action of H2O2and its prevention by lactoferrin from cow's milk. Data are presented as mean ± SEM, n=8. A difference was considered significant if P<0,05.

Figure 3 shows the percentage of 7-AAD positive cells in the culture SHSY5Y cells under the action of H2O2in the presence or absence of different concentrations of lactoferrin from to�Rovigo milk ranging from 0.001 to 1 g/L.

Figure 4 shows the morphology of nuclei in the field of CA2-CA3 of the hypothalamus after DAPI staining.

Examples

Biological activity of fractions of cow's milk, enriched with lactoferrin, exerts the effect of stimulation on the survival of neuronal cells and Narineh processes in vitro.

The process of education narango process includes the growth of axons from neurons and is part of neural development. The effect of fraction of cow's milk, enriched with lactoferrin, narity process was measured using a generally accepted and commonly used bioassay.

Briefly, cells in mouse NS20Y neuroblastoma (DSMZ) were thawed after storage in conditions of freezing, were sown on mattresses for the cultivation of tissues (Falcon) with a density of approximately 27×103cells per cm2and allowed to grow in the presence of DMEM (Gibco) containing 10% FCS (Gibco) and 2 mM L-glutamine (Gibco). Two days after seeding, the cells were separated from the mattress mechanical shaking (by tapping the mattress) and got a unicellular culture, carrying out the suspension several times through a flame sterilized glass pipette. Then the cells were seeded on 13 mm round cover glasses in the presence of DMEM (Gibco) containing 10% FCS (Gibco) and 2 mm L-glutamine (Gibco) with a density of 2000 cells per coverslip. The next day Wednesday for�anjali in DMEM, containing 0.5% FCS, 2 mm L-glutamine and different concentrations of the studied fractions. The next day, cells were fixed in 4% paraformaldehyde and placed the coverslip on a slide.

Got an image for each slide using a microscope (Zeiss Axioplan 2. Digital images were obtained with 25 specific fields across the diameter of the coverslip (20X objective, Axiocam MRc, Zeiss). Cells were counted systematically from the first field at the edge of the coverslip across the coverslip until 100 cells counted. Cells were defined as positive and negative according to the presence narednih processes. Cells were considered positive for Maritim the spikes, if the axon-like processes emanating from the cell body, reaches a length greater than the cell size.

t-test student t-test was used to compare the differences of mean values between one control reference population, and average values for all other processing conditions in each group.

Were checked the following concentration-enriched lactoferrin fraction of cow's milk: 1 µg/l 10 µg/l 100 µg/l 1 mg/l 10 mg/l 100 mg/l and 1 g/l was performed as positive control (CNTF, ciliary necrotrophy factor, 100 ng/ml), a well-known necrotrophy factor is that earlier it was reported that it induces naranya processes in different populations neurone� (Oyesiku and Wigston, 1996 (Oyesiku NM, Wigston DJ: Ciliary neurotrophic factor stimulates neunte outgrowth from spinal cord neurons. J Comp Neurol 1996; 364: 68-77). Basal controls included untreated cells. The results are shown in figure 1.

Protection of neuronal cells from stress

Primary rat cultures of enteric neuronal cells were seeded into the cells and were incubated with different concentrations of enriched lactoferrin fraction of cow's milk within 48 hours. After triple washing with phosphate-saline buffer solution (sterile PBS, 37°C) cells were incubated for 12 hours in cell medium without lactoferrin containing H2O2or vector (control). The protective effects of lactoferrin against induced H2O2the death of neuronal cells was evaluated by measuring the release of neuron-specific enolase (NSE) in a cellular environment. After oxidative stress environment of different groups were collected and centrifuged for 10 min at 12000 revolutions per min (4°C). Collected supernatant was determined NSE released into the culture medium, Immunoradiometric method. The results were expressed in ng/ml As shown in Figure 2, H2O2induced a significant increase of NSE in the medium (p<0,05, n=8). As shown in figure 2, treatment of primary neuronal enteric cells fraction enriched with lactoferrin significantly reduced the H2O2-ind�caravanne the release of NSE (p< 0,05, n=8).

The neuroprotective property of lactoferrin from cow's milk was confirmed using a neuronal-like cell line (neuroblastoma cells SH-SY5Y). Briefly, cells SH-SY5Y were seeded for 24 hours in culture medium was enriched with added lactoferrin fraction at different concentrations for 48 hours. Directly to the cell medium was added for 6 hours (H2O2or vector (control). Cells, in the end, washed with 0.1 M PBS and then collected using trypsin - EDTA. The cell suspension then was combined with the supernatant and centrifuged for 5 min at 2000 rpm. After centrifugation the precipitate was resuspended in 500 ál of 0.1 M PBS. Membrane permeability was assessed using flowcytometry, using as a fluorescent marker 7-AAD. To do this, 200 µl of the cell suspension were incubated for 10 min with 7-AAD prior to the collection using the Bioanalyzer BD FACS Array™. Flowcytometric study using 7-aminoantipyrine D (7-AAD) allowed to distinguish live (7-AAD negative) cells (7-AAD positive) SH-SY5Y cells at late stage of apoptosis/necrosis in response to oxidative stress. The results presented in Figure 3, expressed in % 7-AAD positive cells relative to total number of cells. As shown in Figure 3, H2O2induced mean�diesel increase the percentage of 7-AAD positive cells (p< 0,05, n=6). As shown in figure 3, treatment of cells SH-SY5Y by lactoferrin reduced the H2O2- induced increase in the percentage of 7-AAD positive cells.

Lactoferrin increases the density of neurons and their survival. It protects neuronal cells and inhibits neuronal cell death.

After receiving the results of performed a morphological study. Closely spaced slices of the dorsal and lateral hippocampus at the level of striatum was prepared for assessing the architectonics of the cerebral cortex and hypothalamus and white matter lesions of the brain. Specific cell types were labeled immunochemical to assess specific cellular responses. Performed specific labeling of neurons (NeuN), astrocytes (GFAP) and radial glia (Nestin) in combination with markers of myelination (MBP). Briefly, the method was as follows.

On the 7th (P7) and 21 (P21) postnatal day, respectively, in rat pups from each group were subjected to deep anesthesia using ketalar (50 mg/ml; 0.2-0.5 ml, intraperitoneal (i.p.)). Animals were perfesional intracardiac 0.9% NaCl followed by 4% paraformaldehyde. Removed the brain, weighed it and fixed overnight in 4% paraformaldehyde, then at least 24 hours in 30% sucrose and stored at -80°C until preparation of slices. Coronal sections (10 μm) at the level of the dorsal hippocampectomy on a cryostat (Microm Cryo-Star HM 560M, Microm International, Germany). Each animal received three of the slices at intervals of 200 μm.

Immunohistochemistry: brain tissue was processed to study the immune response against MBP (1:400 mark, city, country (brand city country), using the avidin-Biotin peroxidase complex (ABC; Vector Laboratories, Burlingame, CA, USA). Sections were blocked in 4% bovine serum albumin (BSA brand, city, country), then incubated with primary antibody for 24 h at 4°C, then incubated with secondary antibody (1:200 brand city country), then with a complex of avidin-Biotin (1:200, Vector Laboratories, Burlingame, CA, USA). The reaction was carried out slices with the Chromogen 3,3-diaminobenzidine (DAB brand, city, country) in 0.01% hydrogen peroxide, and then placed under a coverslip.

The same Protocol was used for fluorescent immunohistochemistry nestin (1:500 mark, city, country), GFAP (1:400 mark, city, country) and NeuN (1:200 mark, city, country), except for sections that are not incubated in a complex of avidin-Biotin and DAB.

All experimental groups and their corresponding controls were stained simultaneously. If the processing of the primary antibody was absent, staining occurred.

Quantitative analysis was performed using MetaMorph® imaging system (Meta Imaging Software, Molecular Devices Corporation, Pennsylvania, U. S. A). Values for each animal were combined and calculated CP�the found value is the average±SEM for each group. The measurements were performed on coded glasses that are unknown to the observer, and the codes were not revealed until the analysis is complete. The obtained results are shown in figure 4.

Histological analysis showed that the addition of lactoferrin (LF) Dex pup (n=2) significantly increased the morphology of the nuclei and the density of neurons in the CA2-CA3 field of hippocampus compared with 7-day control rats (Dex control pup at P7). The decrease in the density of neurons in the cortex on day 7 after birth involves the loss of neurons. The density of neurons is similar to the normal control group treated with the carrier (Figure 4). Lactoferrin obtained in this certain time interval of development, will affect the density of neurons in hippocampus and in an area with high sensitivity to lack of nutrition and dependent stress anomalies. This means that the introduction of LF increases the density of neurons and their protection, for example, in young rats retarded (IUGR).

The addition of lactoferrin reduces the expression of genes SOX10 and CRHbp colon on the 21st day after birth.

Collected tissues of the colon of rats treated with dexamethasone and treated or not with oral lactoferrin supplements or control isonitrogenous mixture of amino acids in the process of lactation to the 21st postnatal day. Was extracted with the total RNA content using.�and TriPure. 0.5 μg of RNA (RNA) was subjected to reverse transcription using oligo-dT and Superscript kit and performed real-time polymerase chain reaction (PCR) (Applied Biosystem, TaqMan PCR 7900 HT). Representing the genes of interest were normalized to the constitutive expression of the gene 18S. After normalization we calculated the percentage of difference between the two groups (expressed in percent, n=6). The results showed that the expression of the SOX10 gene in the group of rats treated with Lactoferrin, was reduced by 30% compared with the control group. SOX10 is a marker of glial and neuronal progenitor cells (Wegner M, Stolt CC. From stem cells to neurons and glia: a Soxist''s view of neural development. Trends Neurosci 2005 25(11):583-8; Young et al., Acquisition of neuronal and glial markers by neural crest-derived cells in the mouse intestine, The Journal of Comparative Neurology 2003 456:1-11). It is present in large quantities in the embryonic stages and the initial phases of postnatal development, and its expression then decreases during the ripening process. Our results suggest a better maturation of neuronal progenitor cells to the stage of Mature/differentiated neuronal cells of the enteric nervous system in lactoferrin group on the 21st day of postnatal development. Our results also show a 60% decrease in expression in colon gene hormone-binding protein, corticotropin releasing (CRHbp), lactoferrin group compared with �ontroller. Binding to corticotropin releasing hormone (CRH), CRHbp limits the availability of free and active CRH and thereby reduces its stimulating effect on the motility of the intestine (Saesholtz et al., Mouse models of altered CRH-binding protein expression. Peptides 2001. 22(5):743-51). Observed in our study 60% reduction in the expression of CRHbp gene may contribute to the increase of free and active CRH in the large intestine, the availability of which can stimulate the function of the motility of the intestines in these immature rat pups.

1. Use of the composition for oral administration containing lactoferrin in a concentration of at least 0.1 g/100 kcal of the composition, for the treatment or prevention of disorders associated with delayed development of the enteric nervous system and/or impaired enteric nervous system.

2. The use of claim 1, wherein the composition is selected from the group consisting of food products, products for animals, pharmaceutical compositions, nutritional formulations, nutraceuticals, drinks, dietary supplements, infant formula.

3. The use according to any preceding paragraph, where lactoferrin is delivered in milk composition or enriched with lactoferrin fraction of whey.

4. The use according to claim 1, wherein the composition comprises a protein source, a source of lipids and a source of carbohydrates.

5. The use according to claim 4, where�tocnik protein is present in amounts of 1.4-4.0 g/100 kcal of the composition.

6. Use of the composition according to claim 4, where more than 50% of the mass of the source of protein is a whey protein.

7. The use according to claim 4, wherein the source of lipids provides 30-55% of the total energy value of the composition and/or source of carbohydrates provides 35-65% of the total energy value of the composition.

8. The use according to claim 1, wherein the lactoferrin is present in a concentration range from about 0.01 to 100 g, preferably 0.1 to 50 g, more preferably 2 to 25 g per 100 kcal.

9. The use according to any one of claims. 1, 2, or 4, where the composition further comprises at least about 0.001 wt.% sialic acids, at least about 0.1% omega-3 fatty acids by weight of total amount of fatty acids and/or at least approximately 0.25% omega-6 fatty acids by weight of total amount of fatty acids.

10. The use according to any one of claims. 1, 2, 4-8, where the composition is administered in an amount corresponding to the reception at least 1 g of lactoferrin per kg of body weight per day.

11. The use according to any one of claims.unchou 1, 2, 4-8 to stimulate the development of the enteric nervous system.

12. The use according to any one of claims. 1, 2, 4-8 to restore impaired enteric nervous system.

13. The use according to claim 1, wherein the disorder is selected from the group consisting of a low digestive and/or adsorption capacity.�, gastrointestinal reflux, delayed passage of the intestine, a weakened intestinal barrier function, food intolerance, discomfort in the intestines, solid chair.

14. The use according to any one of claims. 1, 2, 4-8, where the composition is intended for administration to mothers during pregnancy, mothers during lactation, premature or full-term newborns, babies, children, beginners to walk, children and/or adolescents.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to the field of biotechnology, namely to obtaining GLP-2 analogues, and can be used in medicine for treating GLP-2-associated disorders. The analogues of GLP-2 with agonistic activity with respect to GLP-2 receptors have been obtained.

EFFECT: invention makes it possible to increase resistance to proteases, which provides the lower clearance of the obtained analogues and prolongation of their bioavailability in comparison with native GLP-2.

29 cl, 4 tbl

FIELD: medicine.

SUBSTANCE: neonatal young pig's liver is homogenised with water; the homogenate is centrifuged for nuclear settlement; the supernatant is heated, centrifuged again; the cooled supernatant is added with cooled ethanol and centrifuged 15-17 h later; the supernatant is dealcoholised; the produced target product is frozen and stored until used in certain environment.

EFFECT: method enables producing the substance stimulating the injured liver repair.

1 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to biotechnology. Presented is the bacteriocin producing strain Lactobacillus pentosus DSM 21980. The strain is used as a therapeutic agent for controlling gram-negative bacteria, preferentially Enterococci, Coliform bacteria, E. coli, reducing or inhibiting the presence thereof. What is also presented is using the strain for the preventive or curative treatment of gastroenteritis or gastoenterocolitis, infections caused by the above bacteria. The strain can be used as an ingredient of the pharmaceutical composition used as a therapeutic agent. Besides, the strain is used as an ingredient of the food composition applicable as a processing additive added to a starter culture for producing dairy products.

EFFECT: group of inventions provides inhibiting the gram-negative bacteria, preferentially E coli.

15 cl, 4 dwg, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a citrate of a compound described by formula (II) below, and a pharmaceutical composition containing said citrate.

EFFECT: experimental results of the present inventions prove that said citrate can inhibit activity of phosphodiesterase type 5 and can be used for treating erectile dysfunction, for inhibiting thrombocyte aggregation and treating thrombosis, for reducing pulmonary hypertension and treating cardiovascular diseases, asthma and diabetic gastroparesis.

2 cl

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to gastroenterology, and can be used for the treatment of chronic constipation and functional anorexia. For this purpose, as medicinal nutrition used is a milk-vitamin mixture with the following composition (g per 100 g of the product): Proteins 24-26, Fats 27-29, Carbohydrates 33-34, minerals (mg per 100 g of the product), calcium 940-970, phosphorus 780-820, sodium 230-270, potassium 1370-1550, chloride 1270-1350, magnesium 100-125, iron 9.5-10.7, zinc 2.7-3.5, iodine 145-173, copper 76-87, manganese 45-52, vitamins (mcg per 100 g of the product) D3 7.6-8.2, E 6.2-6.8, C 42-46, B1 960-990, B2 1150-1250, Niacin11-15, B6 1370-1440, Folic acid 125-150, Pantothenic acid 2250-2370, B12 1.5-1.9, Biotin 25-31, Choline 40-45.

EFFECT: invention provides an increase of treatment efficiency.

3 ex

FIELD: veterinary science.

SUBSTANCE: declared are a preparation for treating calves' gastrointestinal diseases and a method of treating using the same. The preparation represents a sterile culture fluid produced by culturing the fungus Trametes pubescens (strain 0663) on standard solid and fluid media with sodium selenite and zinc sulphate additionally included into the nutrient medium; that is following by lyophilisation. A method of treating involves adding the preparation to feeding milk. The preparation is introduced in a dose of 180-300 mg per 1 kg of animal's body weight once a day for 4-5 days.

EFFECT: high therapeutic effect of the preparation.

3 cl, 18 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: method includes milling glauconite with the content of rock from 20 to 95%, selection of a fraction of 1.0-10 mcm, preparation of a 40-80% suspension of glauconite in water. The obtained suspension is processed by ultrasound with a frequency of 15-25 kHz for 2-5 minutes. As a result obtained is a glauconite-based enterosorbent, which represents a 40-80% suspension of the glauconite 1.0-10 mcm fraction in water.

EFFECT: obtaining the glauconite-based enetrosorbent, which has the increased sorption ability in the form of a stable water suspension of glauconite.

2 cl, 2 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: group of inventions refers to veterinary science. A method for preparing a herbal therapeutic preparation for treating gastrointestinal diseases in young animals is characterised by the fact that 150-200 g of ground elm bark is placed into a thermally stable flask filled with 500 ml of distilled water, extracted for 3 days in the cold environment; the flask is then placed on a gas or electric stove, connected through a laboratory fridge to a cold water source; distillation of a liquid fraction is followed by sublimation of a solid fraction for 6-8 hours until the particles are carbonised completely; the preparation is collected in a sterile laboratory flask, and then agitated. A method of using the therapeutic preparation produced as described above is characterised by the fact that the preparation is administered into young animals of various species in a dose of 3-25 ml intraperitoneally once a day; in some cases, the preparation is administered again 48-72 hours later. The invention provides the fast and effective action of the preparation ensured by chemical composition and applicability of the preparation by intraperitoneal route of administration; ensuring the fast effect of the pathological process specific for the gastrointestinal tract.

EFFECT: preparation provides anti-inflammatory action on the involved gastrointestinal mucous membranes, relieves the inflammatory process considerably, and thereby reduces the receptor irritation that leads to normalising intestinal peristalsis and reducing diarrhoea.

2 cl, 2 tbl

FIELD: medicine.

SUBSTANCE: first doctor's appointment involves evaluating pulp cavity injuries visually, and prescribing a therapeutic preparation in the form of a paste for inflammation relief. The paste-like therapeutic preparation is Metrogyl Denta gel with either laevomycetin, or metronidazole; the paste is prepared with ex tempore Metrogyl Denta gel with laevomycetin in the following proportions: Metrogyl Denta gel - 0.25-0.35 g; laevomycetin - 0.07-0.09 g (1/5-1/7 of laevomycetin tablet 0.5 g or 2/5-2/7 of laevomycetin tablet 0.25 g), or ex tempore Metrogyl Denta gel with metronidazole in the following proportions: Metrogyl Denta gel - 0.25-0.35 g; metronidazole - 0.05-0.036 g (1/5-1/7 of metronidazole tablet 0.25 g).

EFFECT: method enables reducing inflammation and reducing the number of complications.

4 dwg, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, namely to a composition for preventing or treating gastrointestinal dysmotilities and to a food functional therapeutic composition for preventing or treating gastrointestinal dysmotilities; the above compositions contain mixture of two or more herbs specified in a group consisting of Bupleuri Radix, Coptidis Rhizoma and Glycyrrhizae Radix et Rhizoma.

EFFECT: compositions provide the synergetic effect on preventing or treating gastrointestinal disorders, particularly functional dyspepsia associated with a rate of gastric emptying or a gastrointestinal transit.

6 cl, 5 tbl, 13 ex

FIELD: food industry.

SUBSTANCE: invention relates to a nutritional composition for babies; the nutritional composition contains lactoferrin and probiotics; the lactoferrin amount is 2 - 8 g per 1 litre of the liquid composition ready for consumption or reconditioned dry powder. The nutritional composition is used for alimentation of premature wasted low birth-weight babies or new-born children for intestine maturation stimulation, stimulation of enteral and/or neuronal maturation and/or development, improvement of health of intestine, enhancement of intestine comfort, reduction of colics and pain in the intestine, improvement of cognitive development, strengthening of defence in the subsequent period of life, assistance in maintenance of natural defence or assistance in support of growth of the said babies.

EFFECT: nutritive composition may be represented by a set of parts where the first composition according to the present invention and the second composition according to the present invention are suitable for fulfilling of dietary requirements with different age groups.

14 cl, 3 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to biotechnology. What is presented is a probiotic composition containing a probiotic ingredient, which is presented by Bifidobacterium longum R175 and one or two bacterial species specified in a group consisting of Lactobacillus rhamnosus R11, Lactobacillus helveticus R52 and Lactobacillus plantarum R1012, and a carrier composition. The above carrier composition contains mixture of prebiotics containing inulin and fructose, lactoferrin, inorganic salts, and glutathione as possible. There are also presented versions of the compositions in certain ratio of the above ingredients. What is also presented is a version of the composition containing mixture of probiotic ingredients consisting of Bifidobacterium longum R175 and Lactobacillus rhamnosus R11, a prebiotic ingredient, lacroferrin, inorganic salts and Saccharomyces boulardii. The above compositions are used for supporting and/or recovering the intestinal health and for preventing disbiosis of any origin in mammals, as well as in a method for improving a survival rate of the bacteria Bifidobacterium longum in the gastrointestinal tract.

EFFECT: group of inventions provides the effective colonisation of the gastrointestinal tract with the probiotic ingredients, causes the accompanying anti-inflammatory and immunomodulatory action.

20 cl, 4 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry and represents a pharmaceutical composition for prevention the formation of postoperative cicatrices, surgical adhesions and keloids, containing a biologically active peptide containing an amino acid sequence SEQ ID NO:56, wherein the peptide is found in the concentration of 0.1 mg/ml to 100 mg/ml; and hyaluronic acid with high molecular weight, or a pharmaceutically acceptable salt of hyaluronic acid with high molecular weight, wherein hyaluronic acid with high molecular weight has an average molecular weight more than 300000 Da, and wherein hyaluronic acid is found in the concentration of 0.1 to 10% (wt/wt).

EFFECT: achieving the synergetic effect in relation to reducing the post-operative intra-abdominal adhesions.

6 cl, 2 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, namely to an agent for treating or preventing neuraminidase-resistant rotaviral infection in an individual. The agent for treating or preventing neuraminidase-resistant rotaviral infection in the individual specified in: one or more conjugated linoleic acid (CLA) isomers, vaccenic acid, high-CLA milk fat or fractions thereof, or a cow's milk fat compositions specified in: milk fat, anhydrous milk fat (AMF), phospholipid milk fat fractions high in phospholipids, milk fat fractions high in gangliosides. Using the agent for preparing the composition for treating and preventing neuraminidase-resistant rotaviral infection in the individual. A method of treating and preventing neuraminidase-resistant rotaviral infection in the individual involving administering an effective amount of the agent into the individual in need thereof.

EFFECT: agent is effective for neuraminidase-resistant rotaviral infection in the individual.

23 cl, 2 dwg, 12 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to medicine, particularly toxicology and radiology, to drug preparations based on antioxidant proteins and methods of using them. The pharmaceutical composition for treating toxic conditions wherein the therapeutic effect is ensured by the action of antioxidant, antimicrobial, antitoxic human lacroferrin protein on the human body contains non-replicating nanoparticles of human adenovirus serotype 5 genome with inserted human lactoferrin expressing human lactoferrin in the therapeutically effective amount in the body, and an expression buffer with the particle content not less than 2.33×1011 of physical particles per ml of the expressing buffer. The method of therapy involves administering the composition in the therapeutically effective dose of 7×1011 of physical particles to 7×1013 of physical particles per ml of the expressing buffer per an individual; the composition is administered intravenously.

EFFECT: invention provides the stable therapeutic effect after the single administration of the composition.

17 cl, 14 ex, 4 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, and concerns a pharmaceutical composition for the therapy of acute toxic conditions. The composition for the therapy of acute toxic conditions contains a protein - human lactoferrin, and additionally contains non-replicating nanoparticles with an inserted gene of human lactoferrin, and an expressing buffer in the following proportions per a dose: human lactoferrin 50 to 100 mg; non-replicating nanoparticles - 7×1011 of physical particles; the expressing buffer - the rest, ml. Human lactoferrin is either donor breast milk lactoferrin, or any human lactoferrin.

EFFECT: invention provides fast onset and prolonged antitoxic action.

4 cl, 8 ex, 2 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to introducing dairy fat or an analogue thereof, optionally with at least one additional therapeutic factor, preferentially with lactoferrin or lactoferrin containing a metal ion, preferentially lactoferrin containing iron, preferentially bovine lactoferrin containing iron or a functional version thereof containing metal ions or a functional fragment to inhibit the tumour formation or growth, to maintain or improve one or more parameters, such as leukocyte count, erythrocyte count, or myelocyte count, to reduce the manifestations of cachexia, mucositis and anemia, to stimulate the immune system and to treat or prevent a malignancy and malignant symptoms, and side effects of treating the malignant tumour. Methods and therapeutic use according to the invention may be implemented by the use of a diet (in the form of food products or food additives), nutrient or pharmaceutical composition. There are also presented compositions applicable in the methods according to the invention.

EFFECT: group of inventions provides the higher clinical effectiveness or prevention of the malignant tumour or its symptoms.

39 cl, 7 tbl, 21 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly, the use of human lactoferrin apo-form as an antihypoxant and a hypoxia inducible factor-1 alpha stabiliser.

EFFECT: invention provides the use of the natural iron chelator lactoferrin, no toxicity, hypoallergenicity, an ability to penetrate through the bowel into the blood flow and through the blood-brain barrier.

2 tbl, 1 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to medicine and is applicable in the form of liposome-containing compounds for cancer therapy. A liposome contains one or more phosphatidylcholines, a first derivative of N-(ω)-dicarboxylic acid and phosphatidylethanolamine, an orientation modified derivative of N-(ω)-dicarboxylic acid and phosphatidylethanolamine, an encapsulated therapeutic agent and at least one additional lipid which represents cholesterol or a cholesterol derivative. The orientation modified derivative of N-(ω)-dicarboxylic acid and phosphatidylethanolamine contains an orientation ligand attached to a second derivative of N-(ω)-dicarboxylic acid and phosphatidylethanolamine. The first derivative of N-(ω)-dicarboxylic acid and phosphatidylethanolamine is presented by formula 1,

and the second derivative of N-(ω)-dicarboxylic acid and phosphatidylethanolamine is presented by formula 3, . The orientation ligand preferentially represents transferring, while the encapsulated therapeutic agent is oxalyplatine. The liposome is free from non-modified phosphatidylethanolamine, egg phosphatidylcholine or hydrophilic polymer used to prolong a half lifetime of the liposome in a circulatory channel, and the orientation ligand is other than an intact antibody. What is also described is a method of producing the liposome and a method of treating cancer with using it.

EFFECT: group of inventions provides better target delivery of the therapeutic substance in the tumour cells.

113 cl, 25 dwg, 4 tbl, 30 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the use of a composition for inhibiting lipogenesis and a method for inhibiting lipogenesis. The composition contains lactoferrin and a trivalent chromium compound with lactoferrin being connected with trivalent chromium ions in the complex of lactoferrin-trivalent chromium. The trivalent chromium compound is specified in a group consisting of chromium chloride hexahydrate (III), chromium chloride (III), chromium acetate (III), chromium sulphate (III), chromium picolinate, chromium nicotinate, GTF chromium, complex of chromium and yeast extract and their combination.

EFFECT: invention provides glucose transfer from cells to muscle tissue thereby decreasing stored fat transformed of glucose that leads to achieve a goal of body weight control.

14 cl, 5 tbl, 5 ex

FIELD: food industry.

SUBSTANCE: present invention relates to application of a low-caloric nutritional composition with high protein content for prevention and treatment of mammals' diseases related to muscles involution. The nutritional composition contains, per 100 kcal: at least 12 g of protein substances (with milk whey protein and leucine accounting for at least 80 wt % and at least 11 wt % of the total quantity of protein substances, respectively, at least 20 wt % of the total quantity of leucine being in a free form), a source of fat and a source of digestible carbohydrates. The nutritional composition is administered in the form of 1-2 portions a day; each portion contains 80 - 200 kcal. The composition may be represented in a liquid or a solid form and may additionally contain one or several micronutrients chosen from the group of carotenoids, vitamin A, calcium, magnesium, vitamin B6, vitamin D3, vitamin C, vitamin E, folic acid, vitamin B12, selenium and zinc.

EFFECT: invention allows to produce a composition with improved leucine bioavailability for protein synthesis stimulation in muscles.

33 cl, 4 dwg, 2 tbl

Up!