Edible composition containing indigestible oligosaccharides

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and concerns a composition for treatment or prevention of infection and/or infectious disease of respiratory tracts and the method for application of said composition for specified purposes which involves oral introduction to a mammal of the composition containing a galactose-containing indigestible oligosaccharide and at least 5 wt % of digested galactose saccharide.

EFFECT: invention provides that the active substance is safe and can be included in the dietary intake.

20 cl, 7 ex

 

The present invention relates to a method for prevention and/or treatment of infections of the respiratory tract, which includes the introduction of not digested oligosaccharides.

The respiratory tract is the usual localization of pathogenic microorganisms. Frequent airway infections is a consequence of direct contact with the environment and effects present in the air of microorganisms. There are several types of microorganisms that cause disease in young children.

Respiratory syncytial virus (RSV) is a major cause of serious disease of the lower section of the respiratory tract in children younger and older. Primary RSV infection most often occurs in children aged from 6 weeks to 2 years. RSV is the cause of child bronchiolitis in 75% of cases of occurrence of this disease and child pneumonitis in 40% of cases. Children with increased risk of RSV infection include premature babies and children with bronchopulmonary dysplasia, congenital heart disease, congenital or acquired imunodeficito and cystic fibrosis. Mortality from heart or lung disease among young children hospitalized with RSV infection is 3%-4%. Methods of treatment of a disease caused by RSV are very limited nimi. A serious disease of the lower section of the respiratory tract caused by RSV, often requires significant maintenance treatment, including the introduction of humidified oxygen and artificial ventilation of the lungs.

Infection with parainfluenza virus causes serious illness of the respiratory tract in children younger and older. The share of infectious parainfluenza worldwide accounts for about 20% of all hospitalized children suffering from infectious diseases of the respiratory tract.

Feeding infants breast milk reduces the probability of infection of the respiratory tract. Currently, it is believed that the reason for this situation is the presence in human milk of immunogobulin having neutralizing activity against viruses and other microorganisms.

Treatment of respiratory infections are often associated with certain difficulties. Currently, there are few effective drugs, and these drugs often must be entered directly into the lungs. This procedure causes in newborns significant stress. There is therefore a need for new effective means, which preferably can be entered without causing stress or causing much less stress in children, mladshego and older.

In the scientific literature was recently published article in which it was indicated that baby food containing prebiotics (galactooligosaccharide), probiotics, nucleotides, LC-PUFA and a small amount of lactose, has a beneficial effect on young children suffering from respiratory infections (Rivero et al. (2004), J. Pediatr. Gastroenterol. Nutr. 39: suppl.1, P1121).

The invention

In the execution results of clinical studies conducted in several research centers, the authors of the present invention found that enteral administration of combination of:

a) galactosidase neperebrodivsego oligosaccharide having at least two end sharidny level, of which at least one end sahariano link is chosen from the group comprising glucose and galactose, and at least one terminal saccharide selected from the group comprising galactose and fucose; and

(b) digestible galactose saccharide

helps to reduce the occurrence of infectious diseases of the respiratory tract (see example 6).

The advantage of the method according to the present invention is that the active substance is safe and can be included in the diet. This approach greatly reduces the stress, especially in younger children. Therefore one object of the present invention is one which by oral administration of the nutritional composition, which reduces the likelihood of infectious diseases of the respiratory tract.

The present invention is particularly surprising in view of the fact that until now was considered that low lactose content is essential to prevent respiratory disease in young children. The authors of the present invention have found that the introduction of a food composition containing transplantological and large amounts of lactose, allows particularly effective to prevent or treat respiratory infections.

It was found that galactosialidosis nevereverever oligosaccharide and digestible galactose saccharide necessary for optimal treatment and/or prevention of respiratory infections and/or infectious diseases of the respiratory tract. In addition, lactose contributes to less occurrence of infectious diseases of the respiratory tract.

In addition, the present invention has significant commercial value. Preparation of a composition with a low content of lactose requires, for example, use non-dairy protein (e.g. soy protein) or additional processing of milk to remove lactose (e.g., ultrafiltration). Both options are often undesirable because they increase the cost of the product and may be due to the Oh insufficient caloric intake.

Another object of the present invention is a method of treatment and/or prevention of infections and infectious diseases of the respiratory tract, which includes the introduction of the food composition. The purpose of introducing the active substance of the present invention in the form of the food composition is a reduction in stress and a better reduction of the probability of occurrence of respiratory infections, as specified oligosaccharide has a synergistic effect with long-chain polyunsaturated fatty acids, a combination of choline and zinc, probiotics and/or prebiotics, non-galactosidase neperebrodivsego oligosaccharide. The preferred implementation of the present invention relates to a method of treatment and/or prophylaxis of infections caused by respiratory syncytial virus, which includes the introduction of the child under two years of food composition containing an effective amount of transplantationfollow.

Another object of the present invention is a composition, especially suitable for the treatment and/or prevention of infections and infectious diseases of the respiratory tract, which contains the specified oligosaccharide and immunoglobulin with neutralizing the virus activity, such as immunoglobulin activity, neutralizing parainfluenza virus, or RSV. The decree of the config immunoglobulin preferably get in cows, hyperimmunizing against respiratory Intellinova virus.

Detailed description of preferred embodiments of the invention

The present invention relates to a method of treatment and/or prevention of infections and/or infectious diseases of the respiratory tract, which comprises oral administration to a mammal of a composition comprising galactosidase nevereverever oligosaccharide having at least two end sharidny level, of which at least one end sahariano link is chosen from the group comprising glucose and galactose, and at least one terminal saccharide selected from the group comprising galactose and fucose, and at least 5 wt.% digestible saccharide calculated on the total dry weight of the composition, and the specified saccharide selected from the group comprising galactose and digestible galactosidase saccharide having at least two end sharidny level, of which at least one end sahariano link is chosen from the group comprising glucose and galactose, and at least one terminal saccharide selected from the group comprising galactose and fucose.

Another object of the present invention is a composition intended for the treatment and/or prevention of infections and/or infectious diseases of the respiratory way is, which includes:

a) galactosidase nevereverever oligosaccharide having at least two end sharidny level, of which at least one end sahariano link is chosen from the group comprising glucose and galactose, and at least one terminal saccharide selected from the group comprising galactose and fucose;

b) an immunoglobulin having neutralizing the virus effect; and

(C) a substance, the origin of which is different from human.

This composition further optionally includes:

d) at least 5 wt.% digestible galactose saccharide calculated on the total dry weight of the composition, and the specified saccharide selected from the group comprising galactose and digestible galactosidase saccharide having at least two end sharidny level, of which at least one end sahariano link is chosen from the group comprising glucose and galactose, and at least one terminal saccharide selected from the group comprising galactose and fucose.

Oligosaccharides

The present invention relates to the introduction of galactosialidosis neperebrodivsego oligosaccharide (GAL-oligo), having at least two end sharidny level, of which at least one end sahariano link is chosen from the group comprising glucose and galactose, and kr is ina least one terminal saccharide selected from the group including galactose and fucose. Sugars in GAL-oligo preferably linked in the β-position.

The term “terminal saccharide” means a saccharide associated with one another sharedmem link (such as galactose, glucose, fructose, or fucose). GAL-oligo according to the present invention preferably contains not more than 4 terminal saccharides, preferably not more than 2 sugars. The term “nevereverever oligosaccharides” in the sense used in the present invention, means sugars that are not digested or partially digested in the intestine by the action of acids or digestive enzymes present in the upper division of a human's digestive tract (small intestine and stomach), but are subjected to fermentation by intestinal flora of man.

In a preferred embodiment of the invention GAL-oligo contains at least one terminal galactose and one saccharide selected from the group including at least one terminal glucose and one end fucose. More preferably galactosidase nevereverever oligosaccharide of the present invention contains at least one terminal galactose and at least one terminal glucose. Specified oligosaccharide preferably has 2 end sharidny level and in total 2-60 sharidny links.

GAL-oligo site is preferably selected from the group including transplantological, galactooligosaccharide, lacto-N-tetraaza (LNT), lacto-N-neoteris (neo-LNT), fucosyllactose, fokusirovannyi LNT and fokusirovannyi neo-LNT. Especially preferred embodiment of the invention relates to a method of introducing transplantationfollow ([galactose]n-glucose, where n means an integer from 1 to 60, that is, 2, 3, 4, 5, 6, ..., 59, 60; n preferably denotes 2, 3, 4, 5, 6, 7, 8, 9 or 10). Transplantological (TOS), for example, sold under the trademark Vivinal™ (Borculo Domo Ingredients, Netherlands). Sugars in transplantologiia preferably linked in the β-position.

The composition according to the present invention preferably contains 0.1 to 12 grams GAL-oligo per 100 grams dry weight of the composition, preferably 0.5 to 8 grams, more preferably from 1.0 to 7.5 grams. After recovery of the powder in the liquid, and introducing the child liquid composition specified number of GAL-oligo have the desired effect without causing discomfort in the gut.

Digestible galactose saccharide

The composition used in the method according to the present invention contains digestible carbohydrate, representing digestible galactose saccharide. This composition contains at least 5 wt.% digestible galactose saccharide calculated on the total dry weight of the composition, when the specified eat saccharide selected from the group including galactose and digestible galactosidase saccharide having at least two end sharidny level, of which at least one end sahariano link is chosen from the group comprising glucose and galactose, and at least one terminal saccharide selected from the group comprising galactose and fucose. The composition used in the method according to the present invention, contains at least 5 wt.% digestible galactose saccharide calculated on the total dry weight of the composition, preferably at least 10 wt.%, more preferably at least 25 wt.%.

The term “digestible galactose saccharide” is used in the present invention, means a mono-, di-, tri -, or polysaccharides are digested in the small intestine of a normal healthy person under the action of acids or digestive enzymes present in the upper division of a human's digestive tract (small intestine and stomach). In the method according to the present invention preferably utilize lactose.

Digested by galactose saccharide is preferably lactose. Lactose is at least 50 wt.% carbohydrates in the composition used in the method according to the present invention, preferably at least 75 wt.%, more preferably at least 90 wt.%. The term “carbohydrate”within the meaning of used in the present invention, means digestible carbohydrate in accordance with generally accepted value. The composition used in the method according to the present invention preferably contains at least 10 wt.% the saccharide lactose calculated on the total dry weight of the composition of the present invention, preferably at least 25 wt.%, more preferably at least 40 wt.%, most preferably at least 50 wt.%. To ensure optimal nutrition for the young child, that is, to obtain a composition that best suits the milk man, the method according to the present invention preferably includes the introduction of a composition containing 40-60 wt.% lactose calculated on the total dry weight of the composition.

Another preferred implementation of the present invention relates to the introduction of approximately 2-50 grams of lactose per serving, preferably about 10-25 grams of lactose per serving. One portion is preferably 5-500 ml, more preferably 100-300 ml

The mass ratio of digestible galactose saccharide and galactosialidosis neperebrodivsego oligosaccharide preferably above 1, more preferably greater than 5, more preferably above 10. This ratio is preferably less than 1000, more preferred is entrusted below 100.

The combination of oligosaccharides

In a particularly preferred embodiment of the invention the method according to the present invention includes the introduction of GAL-oligo according to the present invention and the second neperebrodivsego oligosaccharide selected from the group comprising nevereverever dextrins, xylooligosaccharide, arabinopyranoside, glucooligosaccharide, mannooligosaccharide, frukooligosaharidov, fructans type of Leuven (β-D-((2>6)fructofuranosyl)nα-D-glucopyranosid) and fructans of the inulin type (β-D-((2>1)fructofuranosyl)nα-D-glucopyranosid). The second oligosaccharide preferably chosen from the group comprising inulin, hydrolyzed inulin and fructo-oligosaccharides.

The composition according to the present invention preferably contains 0.5 to 12 grams of the second neperebrodivsego oligosaccharide, more preferably 1-8 grams of the second neperebrodivsego of oligosaccharide per 100 grams dry weight of the composition of the present invention. The degree of polymerization (DP) of the second oligosaccharide preferably less than 40, more preferably is in the range from 10 to 30.

The composition according to the present invention contains a total of from 1 to 12 grams of water soluble not digested oligosaccharides (i.e. together with the second, third, etc. water-soluble nevereverever the oligosaccharide or without) per 100 grams of the dry weight of the composition of the present invention, more preferably a total of 2 to 9 grams.

The preferred mass ratio:

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

b) (oligosaccharides with DP 10 to 60):(oligosaccharides with DP 6-9) in both cases, exceed 1.

Both the weight ratio is preferably more than 2, more preferably more than 5.

The method according to the present invention preferably includes the introduction of 0.5 to 10 grams of transplantationfollow with DP 1-10 per 100 grams dry weight of the composition, more preferably 2-5 grams. The composition according to the present invention preferably contains 0.5 to 10 grams of fructooligosaccharide with DP 15-40 per 100 grams dry weight of the composition, more preferably 1-5 grams. The term “fructooligosaccharide” means nevereverever polysaccharide with carbon chain comprising at least 10 units of fructose linked in the β-position.

In another preferred embodiment of the invention the second nevereverever oligosaccharide is acidic oligosaccharide. The term “acidic oligosaccharide” means an oligosaccharide containing at least one acid group selected from the group comprising N-acetylneuraminic acid, N-glycolylneuraminic acid, free or esterified carboxylic acid group, sulfuric acid group and phosphoric acid. Acidic oligosaccharide is m preferably is polyhexes. At least one of the above acid groups are preferably present in an end link of hexose acidic oligosaccharide. Acidic oligosaccharide preferably contains a carboxylic acid into the end link of hexose, with the specified carboxylic acid group can be free or esterified. Methods of obtaining esterified pectin hydrolysates, which can be used in the method according to the present invention, and the corresponding composition described in WO 01/60378 and/or WO 02/42484, which is incorporated into this description by reference.

Acidic oligosaccharide preferably has one, preferably two end link uronic acid, which can be free or esterified. End link uronic acid preferably chosen from the group comprising galacturonic acid, glucuronic acid, guluronate acid, Euronaval acid, mannurone acid, Rybarikova acid and alternova acid. These links can be free or esterified. In an even more preferred variant of the invention, the end link of hexose has a double bond, which preferably is in position With4and C5end link hexose. One of the end links of hexose preferably has a double tie is. End hexose (e.g., uronic acid) preferably has the structure shown below.

The preferred acid end group hexose

where:

R is preferably chosen from the group comprising hydrogen, hydroxyl or acid group, preferably hydroxy (see above); and

at least one group selected from the group R2, R3, R4and R5represents N-acetylneuraminic acid, N-glycolylneuraminic acid, free or esterified carboxylic acid group, sulfuric acid group and phosphoric acid, and the rest of the group R2, R3, R4and R5represent a hydroxyl group and/or hydrogen. One group selected from the group R2, R3, R4and R5preferably represents N-acetylneuraminic acid, N-glycolylneuraminic acid, free or esterified carboxylic acid group, sulfuric acid group and phosphoric acid, and the rest of the group R2, R3, R4and R5represent a hydroxyl group and/or hydrogen. More preferably one group selected from the group R2, R3, R4and R5represents a free or esterified carboxylic acid, and the rest of the group R2, R3, R4and R5represent a hydroxyl group and/or hydrogen; n is an integer and indicates the number of links of hexose (see also below, the degree of polymerization), which can represent any element of hexose. Usually, n is an integer equal to 1-5000, and means the number of links of hexose, and these links hexose preferably are uronic acid, more preferably links the galacturonic acid. The group of carboxylic acids in these links can be free or partially esterified and preferably at least partially methylated.

More preferably R2and R5mean hydroxyl group, R4means hydrogen and R5means a free or esterified carboxylic acid.

Acidic oligosaccharide used in the method according to the present invention has a degree of polymerization (DP) 1-5000, preferably 1 to 1,000, more preferably 2-250, more preferably 2-50, most preferably 2-10. Using the mixture of acidic oligosaccharides with different degrees of polymerization, the average value of DP mixture of acidic oligosaccharides preferably equal 2-1000, preferably 3-250, more preferably 3-50.

Acidic oligosaccharides preferably characterized by a degree of methoxylation of more than 20, preferably more than 50%, more preferably more than 70%. Acidic oligosaccharides preferably have a degree of methylation of more than 20%, preferably more than 50%, more preferably more than 70%.

Acid oligosaccharide is preferably introduced in an amount of from 10 mg to 100 grams per day, preferably from 100 mg to 50 grams per day, more preferably from 0.5 to 20 grams per day.

Respiratory tract infections

The present invention relates to a method of treatment and/or prevention of respiratory tract infections, the cause of which usually are bacteria, viruses or fungi. In a preferred embodiment of the invention the method according to the present invention relates to treatment and/or prevention of respiratory tract infections caused by such pathogens as Pneumococcus, Legionella spp., Streptococcus, Pseudomonas, Staphylococcus, Heamofilis, Mycoplasma, Mycobacteria, chlamydia, Moraxella, Coxiella, Nocardia, Klebsiella, Enterobacter, Proteus, Serratia, Acinetobacter, Orthomyxovirida, Myxovirus, Orthomyxokvirus, Rhinovirus, Echoviruses, Coxsackieviruses, Adenovirus, Parainfluenzavirus, Respiratory Syncytial virus (RSV), Coronavirus, Measles virus, Cytomegalovirus, Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis, Cryptococcus Aspergillus, Mucorales. The method according to the present invention is particularly suitable for the treatment and/or prophylaxis of infections caused by respiratory syncytial virus.

In a preferred embodiment of the invention the method according to the present izaberete the s refers to the treatment and/or prophylaxis of infectious diseases of the respiratory tract, preferably selected from the group including tuberculosis, bronchitis, bronchiolitis, tracheitis, pneumonia, sinusitis, rhinitis, severe acute respiratory syndrome (SARS), fibrinous epiglottitis, histoplasmosis, coccidioidomycosis, blastomycosis, cryptococcosis, aspergillosis, mycomics and lung abscess. Especially preferred embodiment of the invention relates to a method of treatment and/or prophylaxis of viral pneumonia and/or bronchitis.

The method according to the present invention is also suitable for the treatment and/or prevention of symptoms of respiratory tract infections selected from the group including lung irritation, congestion of the lungs, excessive formation of mucus, shortness of breath (i.e. difficulty breathing, especially breathing problems.

A group of subjects to be treated

The method according to the present invention is particularly suitable for the treatment and/or prevention of respiratory infections in children aged 0 to 10 years, preferably in children younger ages 0 to 4 years. The method according to the present invention can be successfully used for the treatment and/or prophylaxis of the aforementioned diseases, infections and symptoms in premature infants (babies born before 37 weeks of pregnancy).

The method according to the present invention is particularly suitable for the treatment and/or prevention of respiratory infections in subjects with impaired immunity, PR is doctitle older people (aged 60 years), subjects infected with human immunodeficiency virus (HIV), subjects suffering from one or more of the following diseases: nephrotic syndrome, multiple myeloma, lymphoma, Hodgkin's disease, subjects with organ transplantation, subjects with chronic heart disease, kidney or lung problems (such as chronic obstructive pulmonary disease (COPD), emphysema, sarcoidosis, cystic fibrosis, bronchiectasis, lung cancer, atelectasis, respiratory disorders, occupational lung disease, asthma), diabetes, and alcoholism. The method according to the present invention can be successfully used for the treatment and/or prophylaxis of subjects suffering from COPD, HIV-infected subjects and/or subjects with diabetes, as these subjects are often weakened by the above disease.

In another preferred embodiment of the invention the method according to the present invention includes the introduction of the compositions of the present invention to subjects, mainly hospitalized subjects, which are connected to a breathing machine or ventilator, or are in the ICU, as these subjects are particularly vulnerable to viral infections.

The composition of food composition

Drug treatments infection is hotelnah ways in children aged 0 to 4 years are often associated with certain difficulties, because many drugs must enter into the lungs. The present invention relates to a method of treatment and/or prevention of respiratory infections, which comprises oral administration of the nutritional composition. Therefore, the method according to the present invention solves the problem associated with the introduction of drugs into the lungs.

Food composition suitable for use in the method according to the present invention preferably contains 10 to 60 EN.% lipids, 5-50 EN.% proteins, 15-90 EN.% carbohydrate. More preferably specified food composition contains 7,5-12,5 EN.% proteins, 40-55 EN.% carbohydrates and 35-50 EN.% fats (EN.% is an abbreviated designation of the energy of interest and indicates the relative amount of calories contributed by each component in the total caloric content of the product).

In addition, the nutritional composition preferably contains at least one long-chain polyunsaturated fatty acid (LC-PUFA), preferably selected from the group comprising eykozapentaenovuyu acid (EPA, n-3), docosahexaenoic acid (DHA, n-3) and arachidonic acid (AA, n-6), as these acids further reduce respiratory tract infections and/or their symptoms. The composition according to the present invention preferably contains AA and DHA, more preferably AA, DHA and EPA. The combination of nevereverever the s oligosaccharides and LC-PUFA of the present invention has a synergistic effect.

The composition according to the present invention preferably contains at least 0.1 wt.%, preferably at least 0.25 wt.%, more preferably at least 0.5 wt.%, more preferably at least 0.75 wt.% LC-PUFA

with 20 and 22 carbon atoms from the total fat content. The content of LC-PUFA with 20 and 22 carbon atoms in the composition of the present invention preferably does not exceed 15 wt.% from the total fat content, preferably not more than 10 wt.%, more preferably does not exceed 5 wt.%

from the total fat content.

The EPA content preferably does not exceed 15 wt.% from the total fat content, more preferably less than 5 wt.%, most preferably does not exceed 1 wt.% and preferably is at least of 0.05 wt.%, more preferably at least 0.1 wt.% from the total fat content. The DHA content preferably does not exceed 10 wt.%, more preferably does not exceed 5 wt.%, most preferably does not exceed 1 wt.% and is at least 0.1 wt.% from the total fat content. The composition according to the present invention preferably contains at least 0.1 wt.% AA, more preferably at least 0.25 wt.% AA, most preferably at least 0.5 wt.% AA in the calculation of the total fat content. The AA content preferably does not exceed the t 5 wt.%, more preferably does not exceed 1 wt.%

from the total fat content.

The composition is intended for administration to adults, can contain large amounts of LC-PUFA. The content of EPA in this case preferably does not exceed 15 wt.% from the total fat content, more preferably not more than 10 wt.% and preferably is at least of 0.05 wt.%, more preferably at least 0.1 wt.% from the total fat content. The DHA content preferably does not exceed 15 wt.%, more preferably does not exceed 10 wt.% and is at least 0.1 wt.% from the total fat content. The composition according to the present invention preferably contains at least 0.1 wt.% AA, more preferably at least 0.25 wt.% AA, most preferably at least 0.5 wt.% AA in the calculation of the total fat content. The AA content preferably does not exceed 15 wt.%, more preferably does not exceed 10 wt.% from the total fat content.

The method according to the present invention does not involve the introduction of a composition derived from milk man. Therefore, the method according to the present invention preferably includes the introduction of the composition containing the substance, the origin of which is distinct from the human and which preferably is a food substance suitable for oral administration human is, more preferable is a cellulose, a carbohydrate, fat and/or protein, non-human, preferably with a plant, animal, microbial or synthetic origin.

Immunoglobulin

The present invention relates also to compositions which are especially suitable for use in the method of treatment and/or prevention of respiratory tract infections, and this composition contains the above nevereverever oligosaccharides and immunoglobulin having neutralizing the virus effect, preferably immunoglobulin, capable of neutralizing the virus is selected from the group including Myxovirus, Orthomyxokvirus, Rhinovirus, Echoviruses, Coxsackieviruses, Adenovirus, Respiratory Syncytial virus (RSV), Coronavirus, Measles virus and Cytomegalovirus. The immunoglobulin is preferably IgA and/or IgG, which is preferably obtained from hyperimmunizing mammal, preferably of the cow. Methods of obtaining these immunoglobulins have hyperimmunizing mammal are well known to the person skilled in the art and described, for example, in UK patent No. 1573995.

Hyperimmunization preferably a mammal immunized with an antigen capable of stimulating the production of antibodies with neutralizing the virus activity, and the virus is chosen from the group comprising Myxovirs, Orthomyxokvirus, Rhinovirus, Echoviruses, Coxsackieviruses, Adenovirus, Respiratory Syncytial virus (RSV), Coronavirus, Measles virus and Cytomegalovirus. In a particularly preferred embodiment of the invention the composition according to the present invention contains an immunoglobulin with RSV neutralizing activity.

The composition according to the present invention contains no milk people. Therefore, the composition of the present invention preferably includes a substance, the origin of which is different from a human, preferably a food substance, more preferably a substance of vegetable, animal, microbial or synthetic origin. Specified substance preferably is a fiber, carbohydrate, fat or protein.

In addition, the composition of the present invention combines at least one substance selected from the group comprising LC-PUFA (described above), digestible galactose saccharide (see above), probiotics (described below), choline (see below), and zinc (see below).

Probiotics

In another preferred embodiment of the invention the method according to the present invention includes the introduction of the above not digested oligosaccharides and probiotic. Probiotic preferably chosen from the group comprising Lactobacillus, Lactococcus, Bifidobacterium, Enterococcus, Propionibacterium, Pediococcus, Bacillus, and Streptococcus, more preferably from the group comprising breast is okolie bacteria and bifidobacteria. Probiotic preferably is a non-pathogenic bacteria that produce lactic acid. The combination of not digested oligosaccharides according to the present invention and probiotic bacteria has a synergistic effect.

Choline and zinc

In another preferred embodiment of the invention the composition according to the present invention contains zinc and/or choline. Zinc and choline stimulate the formation of tissue membranes healthy lung and, thus, increase the immunity to infections. In the method according to the present invention can be successfully used compositions containing zinc and/or choline.

The composition according to the present invention preferably contains 5-500 mg of choline per 100 grams dry weight of the composition, more preferably 20-100 mg of choline, more preferably 40-60 mg of choline. The composition according to the present invention preferably contains 1-100 mg of zinc per 100 grams dry weight of the composition, more preferably 2-50 mg of zinc, more preferably 10-25 mg of zinc.

Examples

Example 1

Packed milk composition for infants with a label indicating that the composition can be successfully used to prevent infection of the respiratory tract respiratory syncytial virus and contains 100 ml of the final product (and 13.1 g of the powder is ka):

8 energy % protein1.4 g (a blend of whey with casein)
45 energy % digestible carbohydrates7.5 g
47 energy % fat3.5 g
transplantological (TOS)0.3 g

Example 2

Packed milk composition for infants in example 1 with the label indicating that the composition can be successfully used to resolve difficult breathing.

Example 3

Packed milk composition for infants in example 1, which further contains 100 ml of the final product (and 13.1 g of powder):

Raftilin HP (Orafti BE)0.1 g
Beydaglariof 1.3×108SOME
Fish oil tuna0.3 gram
40% oil arachidonic acid (DSM Food Specialties, Delft, Netherlands)0.3 gram

Example 4

Packed milk composition for young children by example 3, which is th next contains 100 ml of the final product (and 13.1 g of powder):

Choline6,5 mg
Zinc2 mg

Example 5

Packed milk composition for infants in example 1, which further contains immunoglobulin activity, neutralizing respiratory syncytial virus, which is described in the European patent ER.

Example 6. The effectiveness of transplantationfollow standard songs for babies, designed to prevent respiratory tract infections in children under the age of 1 year

Method. In Italy conducted a clinical study, which involved 7 centers and 56 pediatricians. Immediately after cessation of breastfeeding children were randomized into two groups. Children in group a (n=69) was administered Nutrilon™ 1 or 2, supplemented with oligosaccharides to a final concentration equal to 0.36 g of transplantationfollow/100 ml (Vivinal-GOS™; Borculo Domo Ingredients, Netherlands) and 0.04 g of fructooligosaccharide/100 ml (Raftiline HP™, Orafti, Tienen, Belgium). Children in the control group (n=82) was administered Nutrilon standard™ 1 or 2.

Nutrilon 1™ contains 45 EN.% carbohydrates, 8 n.% proteins and 47 EN.% fat; about 97 wt.% lactose calculated on the total carbohydrate content; 7.3 grams of lactose per 100 ml; about 54 grams of lactose per 100 grams dry weight ready for the position.

Nutrilon 2™ contains 47 EN.% carbohydrates, 10 EN.% proteins and 43 EN.% fat; about 96 wt.% lactose calculated on the total carbohydrate content; 7.9 grams of lactose per 100 ml; about 54 grams of lactose per 100 grams dry weight of the finished composition.

Results. The infants ranged from 2 to 9 months, infants were followed for 6 months. In both groups there were no differences in diet. In group a was detected in a total of 32 cases of infection of the upper respiratory tract. In the control group revealed a total of 60 cases of infection of the upper respiratory tract. Thus, the number of infections of the upper respiratory tract was significantly (p<0,01) lower in group a compared with group C.

Example 7. Sasha

Sachet containing 1 gram of lactose and 0.5 grams of transplantationfollow and designed to add to the liquid food, including fats, proteins and carbohydrates that are created for the intake of the subjects suffering from chronic obstructive pulmonary disease (COPD), or diabetes, the packaging sachet provided with a label indicating that adding the contents of the sachet in the diet reduces the occurrence of infectious diseases of the respiratory tract.

1. Application not digested oligosaccharides and digestible saccharide galacto the s for the preparation of compositions, designed for use in the treatment or prevention of infections and/or infectious diseases of the respiratory tract, which comprises oral administration to a mammal of a composition containing:
a) galactosidase nevereverever oligosaccharide having at least two end sharidny level, of which at least one end sahariano link is chosen from the group comprising glucose and galactose, and at least one terminal saccharide selected from the group comprising galactose and fucose;
b) at least 5 wt.% digestible galactose saccharide calculated on the total dry weight of the composition, where the specified saccharide selected from the group comprising galactose and digestible galactosidase saccharide having at least two end sharidny level, of which at least one end sahariano link is chosen from the group comprising glucose and galactose, and at least one terminal saccharide selected from the group comprising galactose and fucose.

2. The use of claim 1, wherein the composition comprises:
a) 0.1 to 12 g of transplantationfollow with degree of polymerization (DP) from 2 to 10 per 100 g dry weight of the composition;
b) 40-60 wt.% lactose calculated on the total dry weight of the composition;
and more
c) 10 to 60 EN.% lipid, 5-50 EN.% protein and 15-90 EN.% carbohydrate;
d) at least the e one long-chain polyunsaturated fatty acid (LC-PUFA), selected from the group comprising eykozapentaenovuyu acid (EPA, n-3), docosahexaenoic acid (DHA, n-3) and arachidonic acid (AA, n-6);
this mammal is a child aged 0 to 10 years.

3. The use according to claim 1, in which galactosidase nevereverever oligosaccharide comprises at least one terminal galactose and at least one terminal glucose.

4. The use according to claim 3, in which galactosidase nevereverever oligosaccharide is transplantologiia with degree of polymerization (DP) from 2 to 10.

5. The use according to any one of the preceding paragraphs, in which the composition contains fat, carbohydrate and/or protein of plant, animal (other than human), microbial or synthetic origin.

6. The use according to any one of claims 1 or 3-5, in which the composition contains 0.1 to 12 g galactosidase neperebrodivsego oligosaccharide 100 g dry weight of the composition.

7. The use according to any one of the preceding paragraphs, in which infection of the respiratory tract is infection caused by respiratory syncytial virus.

8. The use according to any one of the preceding paragraphs, in which the method includes the treatment and/or prevention of breathlessness.

9. The use according to any one of the preceding paragraphs, in which an infectious disease of the respiratory tract is one the Xia child bronchiolitis and/or pediatric pneumonia.

10. The use according to any one of the preceding paragraphs, in which the composition further contains a second nevereverever oligosaccharide selected from the group including fructo-oligosaccharides, hydrolysed inulin and inulin.

11. The use according to any one of claims 1 or 3 to 10, in which the composition contains at least one long-chain polyunsaturated fatty acid (LC-PUFA)selected from the group comprising eykozapentaenovuyu acid (EPA, n-3), docosahexaenoic acid (DHA, n-3) and arachidonic acid (AA, n-6).

12. The use according to any one of the preceding paragraphs, in which the composition further contains probiotic bacteria selected from the group comprising Lactobacillus, Lactococcus, Bifidobacterium, Enterococcus, Propionibacterium, Pediococcus, Bacillus and Streptococcus.

13. The use according to any one of claims 1 or 3 to 12, in which the method includes introducing a composition containing 10 to 60 EN.% lipid, 5-50 EN.% protein and 15-90 EN.% carbohydrate.

14. The use according to any one of the preceding paragraphs, in which the composition further contains an acidic oligosaccharides.

15. The use according to any one of the preceding paragraphs, in which the method comprises introducing the composition to a child aged 0 to 4 years.

16. The use according to any one of the preceding paragraphs, in which the composition contains immunoglobulin activity, neutralizing respiratory syncytial virus.

17. The use according to any one of preaches the relevant points, in which the composition is administered to a subject suffering from acquired immunodeficiency syndrome (AIDS), chronic obstructive pulmonary disease (COPD), or diabetes.

18. Composition intended for the treatment or prevention of infections and/or infectious diseases of the respiratory tract, which contains:
a) galactosidase nevereverever oligosaccharide having at least two end sharidny level, of which at least one end sahariano link is chosen from the group comprising glucose and galactose, and at least one terminal saccharide selected from the group comprising galactose and fucose;
b) an immunoglobulin having neutralizing the virus action:
c) fat, carbohydrate and/or protein of plant, animal (other than human), microbial or synthetic origin;
d) at least 5 wt.% digestible galactose saccharide calculated on the total dry weight of the composition, and the specified saccharide selected from the group comprising galactose and digestible galactosidase saccharide having at least two end sharidny level, of which at least one end sahariano link is chosen from the group comprising glucose and galactose, and at least one terminal saccharide selected from the group comprising galactose and fucose.

19. Com is azizia on p, which immunoglobulin having neutralizing the virus effect, is an immunoglobulin that is capable of neutralizing the virus is selected from the group including Myxovirus, Orthomyxokvirus, Rhinovirus, Echoviruses, Coxsackievimses, Adenovirus, Respiratory Syncytial virus (RSV), Coronavirus, Measles virus and Cytomegalovirus.

20. The composition according to p or 19, in which the immunoglobulin is obtained from hyperimmunizing mammal.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention presents the method and composition for treatment and-or prevention of infection, and said method includes oral introduction of the composition to a mammal, and said composition involves galactose-containing indigestible oligosaccharide and immunoglobulin of milk or colostrum of hyperimmunised cows.

EFFECT: development of the effective method for the compositions for treatment and-or prevention of infection.

15 cl, 1 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: medicinal agent with activity of alpha interferon represents a conjugate with a molecule of branched polyethylene glycol of general formula: , where: INF - polypeptide of alpha interferon; R - radicals of 2-aminoethanol -HN-CH2-CH2-O-, 3-aminopropanol -HN-CH2-CH2-CH2-O-, homoserine -HN-CH(COOH)-CH2-CH2-O-; n and n1 - identical or different =50-170, wherein residual branched polyethylene glycol molecular weight 5000-15000 Da are covalently bound with amino groups of polypeptide of alpha interferon.

EFFECT: said agent is an effective antiviral and antiproliferative preparation.

2 cl, 3 tbl, 9 ex

Antiviral agent // 2381807

FIELD: medicine.

SUBSTANCE: invention refers to chemical-pharmaceutical industry, namely to preparation of an antiviral agent of brown algae. The antiviral agent contains fucoidane made of brown aglae fucus or laminaria and representind a salt solution to 30 kDa of vegetative polysaccharide complex concentrated 0.01-15% containing fucoidane, laminarane and alginate made of brown aglae fucus or laminaria, with the salt solution containing a preserving agent from the group: sodium benzoate concentrated 0.01-0.3%, or potassium sorbate concentrated 0.02-0.3% or formaldehyde concentrated 0.01-0.3%, and as a salt solution, it contains an aqueous solution of sodium chloride concentrated 0.85-0.95% - the rest. The vegetative polysaccharide complex contains fucoidane, laminarane and alginate in any ratio, preferentially the vegetative polysaccharide complex contains fucoidane concentrated 10-99.9%.

EFFECT: extended range of antiviral activity with respect to: herpes virus types 1 and 2, cytomegalovirus, adenovirus, hepatitis C virus without expressed by-effects.

3 cl

FIELD: chemistry.

SUBSTANCE: present invention relates to piperidine-amino-benzidazoles having formula (I) and to addition salts or stereochemically isomeric forms, where Q is C1-6alkyl optionally substituted with one or two substitutes, each independently selected from a group consisting of trifluoromethyl, C3-7cycloalkyl, Ar2, hydroxyl, Ar2 - oxy-, hydroxycarbonyl, aminocarbonyl, C1-4alkylcarbonyl, aminocarbonyloxy, C1-4alkoxycarbonyl, Ar2(CH2)ncarbonyloxy, C1-4alkoxycarbonyl-(CH2)noxy, mono- or di(C1-4alkyl)aminocarbonyl, aminosulfonyl, mono(C1-4alkyl)aminosulfonyl, or heterocycle selected from a group consisting of pyrrolidinyl, dihydropyrrolyl, imidazolyl, triazolyl, homopiperidinyl, pyridyl and tetrahydropyridyl; or where Q is C1-6alkyl substituted with two substitutes, where substitute is an amino group and the other is C1-6alkyloxycarbonyl; G is -CH2-; R1 is pyridyl optionally substituted with two substitutes selected from a group consisting of hydroxyl, C1-6alkyl; each n equals 1; one of R2a and R3a is C1-6alkyl and the other is hydrogen; when R2a is not hydrogen, R2b is C1-6alkyl and R3b is alkyl; and R3a, R2a, R2b all represent hydrogen; or R5 is hydrogen; t equals 2; Ar2 is phenyl or phenyl substituted with one or more, for example 2 substitutes selected from halogen, C1-6alkyloxy, aminosulfonyl and C1-4alkoxycarbonyl. The invention also relates to a pharmaceutical composition based on compound of formula I and use of the said compounds in making medicinal agents.

EFFECT: novel piperadine-amino-benzimidazoles are obtained, having inhibitory effect on respiratory syncytial virus replication.

10 cl, 3 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel derivatives of aminobenzimidazole and benzimidazole of general formula (I-b-1), additive salt or stereochemically isomeric form thereof, where G is a single bond or C1-10alkanediyl; R1 is halogenphenyl, pyridyl, pyrazinyl, quinolinyl, benzimidazoly or a radical of formula (c-4), where each of the said monocyclic or bicyclic heterorings can be optionally substituted with 1, 2 or 3 substitutes, independently selected from a group consisting of halogen, hydroxy, C1-6alkyl, C1-6alkyloxy, Ar1C1-6alkyloxy, C1-6alkyloxy-CH2-CH2-O-; m equals 2; Q is hydrogen, amino or mono(C1-4alkyl)amino; R3b is hydrogen or C1-6alkyl; R4a is selected from a group of substitutes consisting of hydrogen, Ar2C1-6alkyl, Het- C1-6alkyl, hydroxy C1-6alkyl, (hydroxyC1-6alkyl)oxy C1-6alkyl, C1-6alkyl, (Ar1C1-6alkyloxy)(hydroxy)C1-6alkyl, aminoC1-6alkyl, mono- and di(C1-6alkyl)amino-C1-6alkyl, carboxyl-C1-6alkyl, C1-6alkyloxycarbonyl C1-6alkyl, aminocarbonylC1-6alkyl, (C1-4alkyloxy)2-P(=O)-C1-6alkyl, aminosulphonylC1-6alkyl; R6a is hydrogen or C1-6alkyl; R6b is hydrogen, C1-6alkyl, Ar1 or Ar1C1-6alkyl; R6c is C1-6alkyl; Alk is C1-6alkanediyl; R9, R10, R11 are each independently selected from halogen, cyano, C1-6alkyl, Het-C1-6alkyl, Ar1C1-6alkyl, cyano C1-6alkyl, C2-6alkenyl, R6b-O-C3-6alkenyl, C2-6alkynyl, Ar1, R6b-O-, R6b-S-, R6b-O- C1-6alkyl-SO2-, polyhalo-C1-6alkyl, polyhaloC1-6alkyloxy, polyhaloC1-6alkylthio, R6c-C(=O)-, R6b-O-C(=O)-, N(R6aR6b)-C(=O)-, R6b-O-C1-6alkyl, R6b-O-C(=O)-C1-6alkyl, N(R6aR6b)-C(=O)-C1-6alkyl, R6c-C(=O)-NR6b-, N(R6aR6b)-S(=O)2-, H2N-C(=NH)-, and R10 and/or R11 can also be hydrogen; Ar1 is phenyl; Ar2 is phenyl; Het is a heteroring selected from imidazolyl or morpholinyl. The invention also relates to a pharmaceutical composition based on formula (I-b-1) compound, use of formula (I-b-1) compound to prepare a medicinal agent and a method of producing formula (I-b-1) compound.

EFFECT: novel aminobenzimidazole and benzimidazole derivatives with antiviral activity are obtained.

15 cl, 8 tbl, 31 ex

FIELD: medicine.

SUBSTANCE: invention concerns medicine, namely to vaccinal prevention, and can be used for specific prevention of hepatitis B in children with oncologic diseases in past history. That is ensured by revaccination in the children underwent the primary vaccination, 3-6 months after consolidating chemo- or radiation therapy. Herewith, at first hepatitis B antibody titres are determined. The titre 10 mMe/ml and less enables to administer the vaccine in a dose 0.5 ml. The titres are determined again 30 days later. The titre exceeding 10 mMe/ml, the vaccination is not applied, while the titre 10 mMe/ml ensures to introduce the second additional dose - 0.5 ml of the vaccine. Then 5 months later the titre more than 10 mMe/ml enables to consider the vaccination finished, and the third additional dose 0.5 ml of the vaccine is required with the titre less than 10 mMe/ml.

EFFECT: invention provides formation of steady protective hepatitis B antibody titres that allows to preventing viral infection in given category of patients.

5 ex, 1 tbl

FIELD: veterinary science.

SUBSTANCE: invention relates to veterinary virology and biotechnology. The vaccine contains an active substance and a target additive. The vaccine active substance is represented by a mixture of avirulent refined antigen material from the VNIIZZh strain of cattle rednose virus, Herpesviridae family, Varicellavirus genus, collection of Federal State Institution "Russian National Research Institute for Control, Standardisation and Certification of Veterinary Preparations", "VNIIZZh-DEP", and of avirulent refined antigen material from the VNIIZZh strain of cattle coronavirus, Coronaviridae family, Coronavirus genus, collection of Federal State Institution "Russian National Research Institute for Control, Standardisation and Certification of Veterinary Preparations", "VNIIZZh-DEP", taken at a ratio of 1:1 and in quantities ensuring protective immune activity of each antigen in the animal organism after receipt of the target product injection. With the animals having been immunised the vaccine induces a high level of antigens against the pathogens of cattle rednose and coronoviral infection and is capable to protect varied age and sex group cattle livestock against the above diseases.

EFFECT: with the animals having been vaccinated immunity is generated within 10-15 days after the vaccine re-injection and sustains for at least 6 months.

12 cl, 6 tbl, 3 ex

FIELD: veterinary science.

SUBSTANCE: invention relates to veterinary virology and biotechnology. The vaccine contains an active substance and a target additive. The vaccine active substance is represented by a mixture of avirulent refined antigen material from the VGNKI-4 strain of cattle paragrippe-3 virus, Paramyxoviridae family, Parainfluenza genus, Parainfluenza virus 3 subtype, collection of Federal State Institution "Russian National Research Institute for Control, Standardisation and Certification of Veterinary Preparations", "VGNI-4 DEP", avirulent refined antigen material from the VNIIZZh strain of cattle rednose virus, Herpesviridae family, Varicellavirus genus, collection of Federal State Institution "Russian National Research Institute for Control, Standardisation and Certification of Veterinary Preparations", "VNIIZZh-DEP", and of avirulent refined antigen material from the VNIIZZh strain of cattle coronavirus, Coronaviridae family, Coronavirus genus, collection of Federal State Institution "Russian National Research Institute for Control, Standardisation and Certification of Veterinary Preparations", "VNIIZZh-DEP". The strains are taken at a ratio of 1: 1: 1 and in quantities ensuring protective immune activity of each antigen in the animal organism after receipt of the target preparation injection.

EFFECT: with the animals having been immunised the vaccine induces a high level of antigens; immunity with them is generated within 10-15 days after the vaccine re-injection and sustains for at least 6 months.

15 cl, 7 tbl, 4 ex

FIELD: biotechnologies.

SUBSTANCE: vaccine contains cultural virus raw material, inactivant and oil adjuvant. As virus raw material, vaccine contains mono- or polyversions of blue tongue virus serotypes, which caused epizooty, and multiplied in elective cultures of cells with biological activity of 5.5-8.0 lg TCD (tissue cytopathic dose)50/cm3, at the following ratio of components in vaccine, wt %; cultural raw material of blue tongue virus - 40-60, inactivant-theotropine - 0.02-0.05, oil adjuvant - the rest.

EFFECT: vaccine is harmless, has high immunogenicity.

3 ex

FIELD: medicine.

SUBSTANCE: invention is related to 4-((2)-4'-hydroxybutene-2'-yl)-2-R-6-phenyl-1,2,4-triazolo[5,1-c][1,2,4]triazine-7-ons of common formula (1) ,

where R=H, CH3,SCH3 have antiviral action against herpesvirus of simple type 1 (HSV-1).

EFFECT: new derivatives have useful biological properties.

1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention concerns drugs and covers a combination applicable for treating a respiratory disease representing asthma, acute or chronic bronchitis, emphysema, chronic obstructive pulmonary disease, bronchial hyperactivity or rhinitis, containing effective amount of (a) corticosteroid and effective amount of (b) M3 muscarine receptors antagonist which represents 3(R)-(2-hydroxy-2,2-dithiene-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane in the form of salt containing anion X which is pharmaceutically acceptable anion of mono-or polyvalent acid. There is also disclosed application of 3(R)-(2-hydroxy-2,2-dithiene-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane and corticosteroid for preparing a drug for treating a respiratory disease and the method of treating said respiratory disease.

EFFECT: combinations under the invention provide improved therapeutic effect in treating the respiratory diseases.

21 cl, 1 dwg, 1 tbl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention presents the method and composition for treatment and-or prevention of infection, and said method includes oral introduction of the composition to a mammal, and said composition involves galactose-containing indigestible oligosaccharide and immunoglobulin of milk or colostrum of hyperimmunised cows.

EFFECT: development of the effective method for the compositions for treatment and-or prevention of infection.

15 cl, 1 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (II) and their pharmaceutically acceptable salts and stereoisomers as β2-adrenergic receptor agonists, to a pharmaceutical composition based on the said compounds, a treatment method, to a method of producing said compounds, their use, as well as to crystalline hydrochloride of N-[5-((R)-2-{2-[4-((R)-2-amino-2-phenylethylamino)phenyl]ethylamino}-1-hydroxyethyl)-2-hydroxyphenyl]formamide. The compounds can be used for treating and preventing β2-adrenergic receptor mediated diseases such as asthma and chronic obstructive pulmonary disease. In general formula (II) , R1 is NHCHO, and R2 is hydrogen; or R1 and R2, taken together, represent -NHC(=O)CH=CH- or -CH=CHC(=O)NH-; each of R5 and R6 is independently selected from hydrogen or C1-6-alkyl.

EFFECT: improved method.

14 cl, 3 dwg, 12 ex

FIELD: medicine.

SUBSTANCE: invention covers drugs and concerns a combination intended for treating respiratory disease, containing (a) effective amount of corticosteroid, and (b) effective amount of antagonist of muscarine receptors M3 representing (3R)-1-phenethyl-3-(9N-xantene-9-xarbonyloxy)-1-azoniumbicyclo[2.2.2]octane in the form of salt with an anion X which represents a pharmaceutically acceptable anion of mono- or polyvalent acid. There is also disclosed application of (3R)-1-phenethyl-3-(9N-xantene-9-carbonyloxy)-1-azoniumbicyclo[2.2.2]octane and corticosteroid for making a drug for respiratory disease and the method of treating respiratory disease.

EFFECT: improved therapeutic effect in treating respiratory diseases.

20 cl, 1 dwg, 1 tbl, 7 ex

FIELD: medicine.

SUBSTANCE: invention covers drugs and concerns a combination intended for treating respiratory disease, containing (a) effective amount of corticosteroid, and (b) effective amount of antagonist of muscarine receptors M3 representing (3R)-1-phenethyl-3-(9N-xantene-9-xarbonyloxy)-1-azoniumbicyclo[2.2.2]octane in the form of salt with an anion X which represents a pharmaceutically acceptable anion of mono- or polyvalent acid. There is also disclosed application of (3R)-1-phenethyl-3-(9N-xantene-9-carbonyloxy)-1-azoniumbicyclo[2.2.2]octane and corticosteroid for making a drug for respiratory disease and the method of treating respiratory disease.

EFFECT: improved therapeutic effect in treating respiratory diseases.

20 cl, 1 dwg, 1 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel method of producing tiotropium salts of formula 1 , in which X- can denote a monovalent anion, preferably an anion selected from a group which includes chloride, bromide, iodide, methane sulphonate and trifluoromethane sulphonate, distinguished by that compounds of formula 2 , in which X-can assume values given above, are reacted in a single stage in an acceptable solvent while adding an acceptable base to form a compound of formula 3 in situ, where R is a residue selected from a group which includes N-imidazolyl, N-triazolyl, -O- C(=NR')-NHR", -O-SO2-phenyl, -O-SO2-phenylmethyl, -O-SO2-R', -O-CO-C(methyl)3, -O-CO-phenyl-NO2, chlorine, bromine, -N3 and -O-(P=O)R'" where R' denotes C1-C4alkyl or C3-C6cycloalkyl, R" denotes C1-C4alkyl, C3-C6cycloalkyl or C1-C4alkylene- N(C1-C4alkyl)2, and R'" denotes C1-C4alkyl, -O-C1-C4alkyl, phenyl or -O-phenyl, and R1 and R2 have identical or different values and can be methyl, ethyl, propyl, butyl or phenyl which can optionally be substituted with one or more C1-C4alkyl residues to obtain a compound of formula 4 , in which groups X-, R1 and R2 can assume values given above, and then without its extraction, the compound of formula 4 is reacted with an acceptable acid or with an acceptable desilylation agent with removal of the silyl group in the compound of formula 1. The invention also relates to compounds of formulae 3 and 4.

EFFECT: obtaining tiotropium salts of formula 1 using a simpler and more efficient method which increases output of the product.

8 cl, 9 ex

FIELD: chemistry.

SUBSTANCE: new compounds have formula (I) , where values of radicals R1 - R10 are as given in paragraph 1 of the formula of invention; n equals 2 or 3, --- denotes absence of substitution or a single bond; and denotes a single bond or a double bond, or to salts thereof. The invention also relates to a method of producing compounds of formula (Ic), to a NK2 receptor antagonist, to a pharmaceutical agent, to a method of antagonising the NK2 receptor, to a method of preventing or treating functional gastrointestinal diseases, as well as to use of compounds given in paragraph 1.

EFFECT: obtaining new biologically active compounds with antagonistic effect on the NK2 receptor.

31 cl, 331 ex, 7 tbl

Organic compounds // 2382783

FIELD: chemistry.

SUBSTANCE: invention relates to a compound which is 1-[2-(2-ethyl-2H-tetrazol-5-yl)ethyl]-3-[5-(3-fluoro-4-methanesulfonylphenyl)-4-methylthiazol-2-yl]urea in free form or in form of a pharmaceutically acceptable salt.

EFFECT: composition has inhibitory activity on phosphatidylinositol-3-kinase, which contains the disclosed compound as an active ingredient, to use of the compound to prepare a pharmaceutical composition for treating diseases mediated by phosphatidylinositol-3-kinase and synthesis method thereof.

6 cl, 9 tbl, 154 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula , where Qa is phenyl or heteroaryl, and Qa can possibly carry 1 or 2 substitutes selected from hydroxy, halogen, amino, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkylamino and di-[(1-6C)alkyl]amino; R1 and R2 are each independently selected from hydrogen and (1-6C)alkyl; Qb is phenyl or heteroaryl, and Qb can possibly carry 1 or 2 substitutes selected from hydroxy, halogen, (1-6C)alkyl, (3-6C)cycloalkyl, (1-6C)alkoxy, (1-6C)alkoxycarbonyl, amino, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, amino-(1-6C)alkyl, (1-6C)alkylamino-(1-6C)alkyl, (1-6C)alkylthio, (1-6C)alkylsulfinyl and (1-6C)alkylsulfonyl; where any of the substitutes Qa and Qb defined above, containing a CH2 group which is bonded to 2 carbon atoms, or a CH3 group bonded to a carbon atom, can possibly carry on each of the said CH2 or CH3 group one or more substitutes selected from hydroxy, amino, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkylamino and di-[(1-6C)alkyl]amino; where heteroaryl is an aromatic 5- or 6-member monocyclic ring which can contain up to three heteroatoms selected from oxygen, nitrogen and sulphur, and can be condensed with a benzene ring or a five-member nitrogen-containing ring containing 2 nitrogen atoms; as well as pharmaceutically acceptable salts thereof. The invention also relates to a method of producing formula I compounds, a pharmaceutical composition and use of these compounds for treating conditions mediated by effect of TNF cytokines.

EFFECT: more effective treatment.

13 cl, 3 tbl, 46 ex

FIELD: medicine.

SUBSTANCE: invention refers to new compounds that are lipoxin A4 analogues of general formula (I) and (II) where R1, R2, R3, R4 and R5 have values specified above. The inventions also refers to specific compounds of formula 1 and 11, to pharmaceutical compositions based thereon and to methods of treating inflammatory and autoimmune diseases in a human, and also treating inflammation of pulmonary or respiratory tracts in a human.

EFFECT: higher clinical effectiveness.

40 cl, 14 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention presents the method and composition for treatment and-or prevention of infection, and said method includes oral introduction of the composition to a mammal, and said composition involves galactose-containing indigestible oligosaccharide and immunoglobulin of milk or colostrum of hyperimmunised cows.

EFFECT: development of the effective method for the compositions for treatment and-or prevention of infection.

15 cl, 1 tbl, 4 ex

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