Prevention and treatment of allergic diarrhoea
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to the pharmaceutical industry and represents application of a composition, containing Bifidobacterium breve CNCM I-3865 (NCC2950) for preparation of a composition for prevention of allergic diarrhoea.
EFFECT: invention provides extension of an arsenal of means for prevention of allergic diarrhea.
7 cl, 1 dwg
The technical field to which the invention relates.
The invention relates to the prevention and treatment of allergic diarrhea pathogens.
The level of technology
So far, the diseases that cause diarrhea continue to be a greater global threat to health. Diarrhea strongly affects the quality of life of patients around the world and may pose a threat to life, especially children, elderly and those patients who have violated the possibility of compensation dehydration and severe loss of minerals.
Acute diarrhea is a common cause of death in developing countries and the second most frequent cause of child mortality worldwide. Estimated that it takes the lives of 5 million children under the age of 5 years. The cost of treating diarrhea creates a big load all over burdened health budgets.
The diarrhea can occur for several different reasons, such as infection, including rotavirus, inflammation, allergies and poor nutrition, which cause the most common types of diarrhea, including, for example, secretory, osmotic and motor diarrhea. If the etiological treatment of diarrhea is not possible, for example, by eliminating the pathogen, symptomatic treatment is determined more by the type of diarrhea than the underlying factor.
In the last few decades, there is s lot of attention has earned the use of probiotics as a safe and accessible form of treatment of gastrointestinal diseases. Probiotics have been successfully used in the treatment of diarrhea caused by Rota-virus and other viral infections. Bacteria used for the treatment of viral diarrhea, belong to the genera Lactobacillus and Bifidobacterium. therapeutic activity of some probiotic bacteria in rotavirus gastroenteritis was attributed to their ability to stabilize and strengthen the barrier function of the mucous membranes, to produce substances with antiviral activity and to stimulate local specific and nonspecific immunity. Significant differences were noted between the different strains on the effectiveness and mechanism of action.
For example, in the early 1990s, Saavedra et al. when monitoring 29 children over 18 months. in the Department of chronic diseases one of the hospitals in the US found that using a combination of Bifidobacterium lactis and Streptococcus thermophilus reduces the incidence of diarrhea and isolation of rotavirus (Saavedra et al., Lancet 344, 1046:1994). However, in other tests using bacteria, the results were less certain (Thibault et al., J Ped Gastro Nutr 39, 147; 2004).
Recently it was found (EP 08172263.9), for the treatment or prevention of diarrhea caused by rotavirus infection, you can use the strain of Bifidobacterium breve CNCM I-3865 (NCC2950).
Unlike rotavirus diarrhoea, in which symptoms are caused by a pathogen, when allergic dear is e, in particular associated with food allergies, certain foods can cause the same reaction as taking laxatives.
Food Allergy is a serious health issue in modern society. It occurs in all age groups, but especially for children. From 6 to 8% of children suffer from at least one food Allergy. In adults, it occurs less frequently than in children, however, about 4% of adults suffer from food allergies.
In addition to patients with confirmed diagnosis of food Allergy there are a significant number of individuals (35%), suffering from hypersensitivity to one or more food allergens (R.J. Rona et al., 2007, J. Allergy din. Immunol. 120:638-646).
Long-term allergic diarrhea can weaken the patient, can cause severe dehydration and loss of minerals such as potassium, which can impede the filling of the body with necessary nutrient.
Allergic diarrhea now usually treated, eliminating from the diet food allergens, and/or symptomatically by rehydration and the introduction of the minerals that can cause a significant deterioration in the quality of life and increased costs in the health system. Therefore, it is desirable to have such a composition that would prevent and/or treat allergic diarrhea without fear FOB is cnyh effects and which, therefore, could be included in food products.
From the foregoing it is seen that there is still a need for compositions having effective against allergic diarrhea and suitable for inclusion, for example, in foods for young children.
In this regard, the present invention is to improve the existing situation and the provision of such a composition that satisfies these needs.
The authors of the present invention unexpectedly found that Bifidobacterium breve CNCM I-3865 (NCC2950) allows to achieve this goal.
It is increasingly clear that the specific healing effect of probiotic bacteria is usually impossible to predict, based on the type of bacteria.
In particular, the authors of the present invention discovered that a certain strain of Bifidobacterium breve, originally isolated from the milk man, namely C. breve CNCM I-3865 (NCC2950), is highly efficient in the prevention and treatment of allergic diarrhea. It is noteworthy that it retains its activity even in non-replicated form.
The strain of Bifidobacterium breve CNCM I-3865 (NCC2950) deposited in the National collection of cultures of microorganisms of the Pasteur Institute (Institut Pasteur, 25 roe du Docteur Roux, F-75724 PARIS Cedex 15) in accordance with the Budapest Treaty.
It is noteworthy that Bifidumbacterium breve CNM I-3865 (NCC2950) were also effective in diarrhea, caused by rotavirus infection. Therefore, Bifidobacterium breve CNCM I-3865 (NCC2950) is exclusively active in the treatment or prevention of diarrhea of various etiologies, namely allergic and rotavirus.
Accordingly, in the first aspect of the present invention presents a composition comprising Bifidobacterium breve CNCM I-3865 (NCC2950), for the treatment or prevention of allergic diarrhea.
In the second aspect of the present invention presents the use of Bifidobacterium breve CNCM I-3865 (NCC2950) in the manufacture of a composition for the prevention or treatment of allergic diarrhea.
In the third aspect of the present invention presents a method of prevention or treatment of allergic diarrhea, including introduction to the needy in the subject a therapeutic amount of Bifidobacterium breve CNCM I-3865 (NCC2950).
To test the effectiveness of Bifidobacterium breve CNCM I-3865 (NCC2950) in vivo for the prevention of allergic diarrhea used a model of allergic diarrhea in mice (E.V. Brandt et al., JCI 2003; 112(11); 1666-1667). After sensitization (2 intraperitoneal injections of ovalbumin (OVA) and sulphate of aluminium and potassium with an interval of 14 days (day 0 and day 14) male Balb/c mice did provoke sample introduction oral OVA 6 time (days 27, 29, 32, 34, 36, 39), what caused transient symptoms (diarrhea) and immunological parameters (plasma concentrations of total IgE, OVA-specific IgE, is noteasy 1 mastocytes mouse). Bifidobacterium breve CNCM 1-3865 (NCC2950) was administered gavage 4 days before sensitization with OVA (days -3, -2, -1, 0, and days 11, 12, 13 and 14) and in the period of provocation (days 23-39) in a daily dose of bacteria is about 109SOME 1 mouse.
Brief description of figures
Figure 1 presents the average diarrhea was observed in OVA sensitized mice treated or saline or OVA or OVA-treated after processing of live bacteria Bifidobacterium breve CNCM 1-3865 "(NCC2950). Median ± sustainable assessment SD: 3rd test - saline = 0±0, OVA=1±1,19, live NCC2950=1±0; 4-I test - saline = 0±0, OVA=3±1,19, live NCC2950=1±1,19; 5-I sample - saline = 0±0, OVA=3±1,19, live NCC2950=3±1,19; 6-I sample - saline = 0±0, OVA=5±0,6, alive NCC2950=3±0.
Disclosure of inventions
Because infants and young children are particularly susceptible to food allergies, the composition of the present invention may be intended for infants and young children. In accordance with the definitions given in article 2 of the Directive the European Commission 2006/141/EC of 22 December 2006 on infant formula and their modifications, "breast" are children under the age of 12 months, while younger children are children aged 1 to 3 years.
The term "children" covers the age group from 1 to 14 years.
Of course, the compositions of the present invention can be used for adolescents (15-17 years old) or adults (18 years and older).
"About ICICI" means preparations of microbial cells or components of microbial cells, beneficial to health and well-being of the host (Salminen S, Ouwehand, A., Benno Y. et al. "Probiotics: how should they be defined" Trends Food Sci. Technol. 1999, 10:107-10).
All percentages are mass, unless otherwise specified.
Compositions of the present invention can be any entities that need it.
Such actors can be people or animals, in particular Pets. Entities may belong to any age group, such as infants, children, younger or older, adolescents or adults.
Compositions of the present invention contain a strain of Bifidobacterium breve CNCM 1-3865 (NCC2950) in an amount sufficient to at least partially cure allergic diarrhea. Amount sufficient to achieve this purpose, is defined as "therapeutically effective dose". Effective for this purpose, the amount depends on a number of factors known in the art, such as severity of disease, weight and General condition of the consumer and the influence of the matrix composition.
For prophylactic use Bifidobacterium breve CNCM I-3865 (NCC2950) assigned to the consumer is exposed to or at risk of allergic diarrhea in an amount sufficient to at least partially reduce the risk of allergic diarrhea. This number is defined as a "prophylactically effective dose"beautiful hotel not far as the exact number depends on a number of factors, depending on the patient, as the patient's condition, weight and influence of the matrix composition.
Specialists in this field should be able to find effective therapeutic dose and/or effective dose for prevention.
In General, the compositions of the present invention contain a strain of Bifidobacterium breve CNCM I-3865 (NCC2950) in a therapeutically effective dose and/or prophylactically effective dose.
The probiotic Bifidobacterium breve CNCM 1-3865 (NCC2950) can be administered to the subject in the form of a composition, for example, at a daily dose equivalent to 108SOME. Infants it is convenient to introduce in the composition formula, mixture for infants, which give complementary foods, or milk for the younger infants.
As a rule, Bifidobacterium breve CNCM 1-3865 (NCC2950) is introduced in an amount equivalent to from 103up to 1012CFU/g (dry weight), more preferably from 107up to 1011CFU/g
The expression "equivalent to..." covers the possibility that the bacteria are alive, rereplacenocase or dead. In other words, the number of bacteria is expressed in colony-forming ability of the number of bacteria, as if all the bacteria were alive regardless of whether they actually live, rereplacenocase or dead, or a mixture of any or all of these forms.
In one embodiment of the present imaging is the acquisition of at least 95%, more preferably at least 99% and even more preferably all cells of Bifidobacterium breve CNCM I-3865 (NCC2950) are rereplacenocase.
To do this, they can be transferred in a non-replicated form any of the methods known to experts in this field. Described in the literature techniques of translation probiotic strains in a non-replicated form include, for example, heat treatment, irradiation, UV irradiation or treatment with chemical agents such as formalin or paraformaldehyde. Preferred methods that do not require the addition of reagents. In particular, for preparations containing milk or infant formula, the preferred heat treatment, as it still is to reduce the bacterial load. It does not require any additional processing stages.
Rereplacenocase probiotic microorganisms have the advantage that they are much easier to handle than with the living. In addition, they are more stable during storage and do not require too tough package.
Rereplacenocase probiotic microorganisms contribute to the development of a wide range of functional food, which by their nature do not allow you to add live probiotics without additional measures to protect them. This is important, for example, upon receipt of grain bars, ruchovich juices, pasteurized beverages, stable in storage of beverages and other
In addition, the use of live probiotics, for example, in individuals with a weakened immune system may be limited because of the potential risk of bacteremia. Besides inanimate probiotics are much better tolerated by persons with weakened immune systems.
In addition, adding rereplacenocase probiotic microorganisms tolerate hot recovery, for example, powdered nutritional compositions.
"Rereplacenocase" means that the classical methods of seeding are not detected viable cells and/or colony-forming units. The classical methods of seeding are given in the manual of Microbiology: James Monroe Jay, Martin J Loessner, David A. Golden. 2005. Modem Food Microbiology. 7 th ed., Springer Science, New York, N.Y. 790 p. As a rule, the absence of viable cells can be demonstrated as follows: no visible eyes colonies on plates with agar or absence of turbidity of the liquid nutrient medium after inoculation of the bacterium preparations at various concentrations ("rereplacenocase designs) and incubation under appropriate conditions (aerobic or anaerobic atmosphere for at least 24 h).
The composition can be added prebiotics. Prebiotics can support the growth of Bifidobacterium breve CNCM I-3865 (NCC2950). Prebiotics can also Deiss who participate sinergetice with other viable probiotic bacteria which may be present in the composition, or beneficial bacteria in the gut.
"Prebiotics" means nevereverever nutrients that promote the growth of probiotics, or healthy bacteria in the gut. They are not broken down in the stomach and/or upper intestine or not absorbed in the gastrointestinal tract consuming their faces, but are subjected to fermentation of the gastro-intestinal microflora and/or probiotics. The definition of prebiotics, for example in Glenn R. Gibson and Marcel B. Roberfroid. Dietary modulation of the human colonic microbiota: introducing the concept ofprebiotics. J. Nutr. 1995 125:1401-1412.
Prebiotics, which can be used in accordance with the present invention have no special limitation and include all food substances that promote the growth of probiotics, or healthy bacteria in the gut. Prebiotics are preferably selected from the group consisting of oligosaccharides, optionally containing fructose, galactose, mannose; dietary fiber, particularly soluble fiber, soy fiber; inulin; and mixtures thereof. The preferred prebiotics are fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS), isomaltooligosaccharide (IOS), xylooligosaccharide (XOS), soybean oligosaccharides, glycosylceramide (GS), lactosucrose (LS), lactulose (LA), platinochloride (the AO), maltooligosaccharides (MOS), gums and/or their hydrolysates, pectins and/or their hydrolysates.
In the song, you can add more probiotics. Additional probiotics can be viable or nerealizirane, or a mixture of both. All probiotic microorganisms can be combined with Bifidobacterium breve CNCM I-3865 (NCC2950). Preferably such added probiotic is selected from the group consisting of the genera Bifidobacterium, Lactobacillus, Lactococcus, Enterococcus, Streptococcus, Propionibacterium, Pediococcus, Escherichia coli, Debaryomyces, Kluyveromyces, Saccharomyces, Schizosaccharomyces, Zygosaccharomyces, Yarrowia, Candida, in particular, is selected from the group consisting of the species Bifidobacterium longum, Bifidobacterium lactis, Bifidobacterium animalis, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium bifidum, Bifidobacterium adolescentis, Lactobacillus acidophilus, Lactobacillus casei. Lactobacillus paracasei, Lactobacillus salivarius, Lactobacillus plantarum, Lactobacillus fermentum, Lactobacillus johnsonii, Lactobacillus reuteri, Lactobacillus gasseri, Lactobacillus rhamnosus, Lactococcus spp., as Lactococcus lactis, Lactococcus cremoris, Lactococcus diacetylactis, Enterococcus faecium, Enterococcus faecalis, Saccharomyces cerevisiae, Saccharomyces boulardii, Schizosacchromyces pombe, Kluyveromyces lactis, Yarrowia lypolitica or mixtures thereof; preferably is selected from the group consisting of Lactobacillus johnsonii (NCC533; CNCM I-1225), Bifidobacterium longum (NCC490; CNCM I-2170), Bifidobacterium longum (NCC2705; CNCM I-2618), Bifidobacterium longum (NCC3001; ATCC BAA-999), Bifidobacterium lactis (NCC2818; CNCM I-3446), Bifidobacterium breve (strain), Lactobacillus paracasei (NCC2461; CNCM I-2116), Lactobacillus rhamnosus GG (ATCC 53103), Lactobacillus rhamnosus LPR (NCC4007; CGMCC 1.3724), Enterococcus faecium SF 68 (NCIMB 10415) and mixtures thereof. All these PR the antibiotics can be added to a viable or saralicious.
Food products according to the present invention include dairy products like milk products, e.g., yogurt, buttermilk, etc.; ice cream; evaporated milk; milk; cream; flavoured milk drinks; drinks from whey; toppings (apical toppings); cream substitutes for coffee; chocolate; cheese products; soups; sauces; sauce; spices; puddings; custard; child nutrition; nutrient mixture, as it is full of mixture, e.g., for infants, children, adolescents, adults or the elderly; cereals and cereal bars.
Drinks include, e.g., drinks based on milk or yogurt, fermented milk drinks, coffee, protein drinks, tea, energy drinks, soy drinks, fruit and/or vegetable drinks, fruit and/or vegetable juices.
Similarly, the composition may be administered orally, interline and/or parenteral (e.g., subcutaneously, intramuscularly).
The composition of the present invention can optionally contain a source of protein, a source of carbohydrates and/or source of lipids.
For specific clinical applications, in particular parenterally, it may be desirable to obtain compositions that do not contain a carbohydrate source.
Because the allergens that cause allergic reaction, usually are food proteins or enter them from the Tav, special attention is given to the composition of the source of protein in the compositions intended for allergic patients. In General, the type of protein that is present in the composition, should not cause allergic reactions. Therefore, sources of protein can vary depending on the type of Allergy, subject to prevention or treatment using compositions of the present invention.
You can use any suitable dietary protein, for example, animal proteins (proteins of milk, meat and egg proteins or their hydrolysates; vegetable proteins (soy protein, wheat protein, rice, peas) or their hydrolysates; mixture of free amino acids; or combinations thereof. In some cases, the preferred milk proteins such as casein and whey, and soy proteins or their hydrolysates. If the protein source is milk protein or fraction of milk protein, it may be, for example, sweet whey, acid whey, α-lactalbumin, β-lactoglobulin, bovine serum albumin, acid casein, Caseinates, α-casein, β-casein, γ-casein. Of course, you can use a combination of different protein sources.
As for whey protein, the protein source may be acid whey or sweet whey or their mixture, which may include α-lactalbumin and β-La is noglobulin in any desired ratio. However, especially if the composition is a baby pitatelnaya mixture, the protein source is preferably modified sweet whey. Sweet whey is a readily available by-product of cheese making and is often used in the manufacture of infant formula based on cow's milk.
Proteins can be intact or gidrolizovannykh either in the form of a mixture of intact and hydrolysed proteins. Sometimes it is desirable to use fully or partially hydrolyzed protein (degree of hydrolysis of from 2 to 20%). At the stage of hydrolysis can be potentially allergenic food proteins. Therefore, the inclusion of hydrolyzed proteins may be useful for people suffering from allergies or at risk of allergies.
If you need hydrolysed proteins, the process of hydrolysis can be performed anywhere by any known method. For example, hydrolyzed whey protein can be obtained by enzymatic hydrolysis fractions of whey in one or several stages.
If the composition of the present invention contains a source of protein, the protein or protein equivalent in the composition is typically 1.6 to 7.5 g/100 kcal of the composition.
In particular, nutritious source of protein mixtures must meet the minimum requirements for sod is the neigh of essential amino acids.
If the composition contains a source of carbohydrates, the carbohydrates do not have special restrictions. You can use any suitable carbohydrates, for example, sucrose, lactose, glucose, fructose, solid corn syrup, malto-dextrins, starch and mixtures thereof. You can use a combination of different sources of carbohydrates. Carbohydrates should preferably provide from 30% to 80% of the caloric content of the composition. For example, the composition may contain a source of carbohydrate in the amount of 9 to 18 g/100 kcal of the composition.
If the composition contains a source of lipids, the lipids do not have special restrictions. If the composition contains a source of lipids, a source of lipids can provide from 5% to 70% of the caloric content of the composition. You can add long-chain n-3 and/or n-6 polinenasyschennye fatty acids, such as docosahexaenoic acid (DHA), arachidonic acid (ARA) or eicosapentaenoic acid (EPA). Suitable lipid profile can be achieved using a mixture of rapeseed oil, corn oil, sunflower oil with a high content of oleic acid and oil with medium chain triglycerides. The composition may contain a source of lipids in the amount of 1.5 to 7 g/100 kcal of the composition.
The composition may also contain all vitamins and minerals, which are considered essential in egene the nom diet and in dietologicheskie a considerable amount. The presence and amount of specific minerals and vitamins varies depending on subject to treatment of a subject.
If necessary, the composition may contain emulsifiers and stabilizers, such as soybean lecithin, esters of mono - and diglycerides citric acid and other
The composition optionally may contain other substances that can have a useful effect, such as cellulose, lactoferrin, nucleotides, nucleosides, etc.
Bijidobacterium breve CNCM I-3865 (NCC2950) can be grown in any suitable way and prepare to add to the composition, for example, by the method of freeze or spray drying.
On the other hand, live probiotic microorganisms can be provided in encapsulated form.
As it turned out, encapsulating bacteria provides therapeutic and technical advantages. Encapsulation increases the survival rate of the bacteria and thus the number of live bacteria that reach the intestine. In addition, bacteria are released gradually, which provides the duration of action of bacteria on the health of the subject. Bacteria can be subjected to microencapsulation, for example as described in FR 2443247 (Societe des Produits Nestle), incorporated by reference. In short, the bacteria can be dried by sublimation or sputtering and Zack is ucity in the gel.
Specialists in this field should understand that they can freely combine all the described features of the present invention without going beyond it. In particular, the characteristics described for the application of the present invention can be applied to the compositions of the present invention and Vice versa.
1. The use of a composition containing Bifidobacterium breve CNCM I-3865 (NCC2950), for the preparation of compositions for the prevention of allergic diarrhea.
2. The use according to claim 1, where the composition is a drug, a therapeutic nutritional composition, infant formula, formula for feeding infants, milk for the younger infants, nutritional product, animal feed, nutraceuticals, beverage and/or biologically active food Supplement.
3. The use according to claim 1, where the composition contains Bifidobacterium breve CNCM I-3865 (NCC2950) in an amount equivalent to from 103up to 1012CFU/g dry weight.
4. The use according to claim 3, where the composition contains Bifidobacterium breve CNCM I-3865 (NCC2950) in an amount equivalent to from 107up to 1011CFU/g
5. Use according to one of claims 1, 3 or 4, where at least 95%, preferably 99%, and even more preferably all bacteria Bifidobacterium breve CNCM I-3865 (NCC2950) are not replicated.
6. The use according to claim 1, where the composition further comprises at least one prebiotic in an amount of from 0.3 to d is 6 wt.% by weight of the composition.
7. The use according to claim 2, where the composition is a dietary Supplement and contains from 104up to 1012CFU Bifidobacterium breve CNCM I-3865 (NCC2950) per unit dose.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to chemical-pharmaceutical industry, particularly to method of treatment of dermatological allergic state. Proposed method comprises injection of efficient amount of [4-(5-aminomethyl-2-fluorophenyl)piperidine-1-silt][7-fluorine-1-(2-metoxyethyl)-4-trifluorometoxy-1H-indol-3-il]methanon or its appropriate N-oxide, pharmaceutically acceptable salt or solvate.
EFFECT: higher efficiency.
5 cl, 1 ex, 1 tbl
SUBSTANCE: invention relates to an agent for preventing and/or treating an allergic disease selected from pollinosis, allergic rhinitis, allergic conjunctivitis, atopic dermatitis and asthma, which is a low-molecular polysulphated hyaluronic acid derivative.
EFFECT: obtaining a low-molecular polysulphated hyaluronic acid derivative.
15 cl, 103 dwg, 17 tbl, 55 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutics and medicine and concerns preparing a fast-acting effective and safe agent for treating rhinitis. Solving the problem provides the agent for treating rhinitis, particularly allergi rhinitis containing C-type natriuretic peptide (CNP) and/or B-type natriuretic peptide (BNP) as an active ingredient.
EFFECT: invention provides the notable health improvement in rhinitis, particularly in allergic rhinitis, and besides, the therapeutic effect, ensures fast and prolonged action, and gives no local side effects.
21 cl, 7 ex, 7 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: what is presented is using a composition containing galactooligosaccharide, fructooligosaccharide and uronic acid oligosaccharide in preparing a composition for oral administration into an infant for preventing the local administration of corticosteroids and/or preventing the administration of a calcineurin inhibitor into the above infant, wherein uronic acid oligosaccharide represents a pectin degradation product and/or an alginate degradation product, and wherein using the corticosteroids and/or administering the calcineurin inhibitor is applicable for treating eczema, infantile eczema, atopic dermatitis, dermatitis herpetiformis, contact dermatitis, seborrheic dermatitis, neurodermatitis, psoriasis and intertrigo. Particularly, the composition is a nutritional composition.
EFFECT: what is shown is reducing probability of the local administration of corticosteroids and dermatological preparations to be required for the purpose of preventing the above skin diseases, or reducing the length of using the corticosteroids.
5 cl, 2 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to naphthalene carboxamide derivatives of general formula I which possess the properties of protein kinase or histone deacetylase inhibitors. The compounds can find application for preparing a drug for treating inflammatory diseases, autoimmune diseases, oncological disease, diseases of the nervous system and neurodegenerative diseases, allergies, asthma, cardiovascular diseases and metabolic diseases or disease related to hormonal diseases. In general formula I: , Z represents CH or N; each of the groups R1, R2 and R3 represents hydrogen, halogen, alkyl, alkoxy or trifluoromethyl; R4 represents or X represents a benzene ring or a pyridine ring; R5 represents one or more substitutes specified in a group consisting of hydrogen, halogen, alkyl, alkoxy or trifluoromethyl. The invention also refers to a method for preparing the above compounds, a pharmaceutical preparation and using them.
EFFECT: preparing the compounds which possess the properties of protein kinase or histone deacetylase inhibitors.
13 cl, 10 tbl, 6 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutical industry and represents a complex of biologically active substance for treating allergic diseases of various genesis, characterised by the fact that it has been recovered from cod liver oil by gradual fractionation from ballast lipids by extraction in a two-phase oil and water extractant, centrifugation and ultrafiltration or diafiltration through a material with separation limit 25 kDa, and contains peptides 30-55%, amino acids 40-65%, carbohydrates 2-8%, micro and macroelements 2-13%.
EFFECT: invention provides the drug spectrum broadening.
8 ex, 3 tbl
SUBSTANCE: invention relates to novel of 2,4-pyrimidine diamine compounds of formula I, which inhibit degranulation of immune cells and can be used in treating cell reactions mediated by FcεRI or FcγRl receptors. In formula (I) each R2 and R4 is independently phenyl substituted with one or more R8 groups or a heteroaryl selected from a group consisting of , where the heteroaryl is optionally substituted with one or more R8 groups and at least one of R2 and R4 is a heteroaryl; R5 is selected from a group consisting of (C1-C6)alkyl, optionally substituted with one or more identical or different R8 groups, -ORd, -SRd, fluorine, (C1-C3)halogenalkyloxy, (C1-C3)perhalogenalkyloxy, -NRcRc, (C1-C3)halogenalkyl, -CN, -NO2, -C(O)Rd, -C(O)ORd, -C(O)NRcRc, -C(NH)NRcRc, -OC(O)Rd, -OC(O)ORd, -OC(O)NRcRc; -OC(NH)NRcRc, - [NHC(O)]nORd, R35 is hydrogen or R8; each Y is independently selected from a group consisting of O, S and NH; each Y1 is independently selected from a group consisting of O, S and NH; each Y2 is independently selected from a group consisting of CH, CH2, S, N, NH and NR37. Other values of radicals are given in the claim.
EFFECT: improved efficiency.
19 cl, 6 tbl.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to new 2-S-benzylpyrimidine derivatives having CRTH2 receptor antagonist activity. In formula 1: R1 means -CO2H; R4a and R4b mean hydrogen; W means -C(O)NR7-; R2 and R3, each independently mean F; Cl; Br;-NR10R11 or (C1-C6)alkoxy, optionally substituted by 1-3 halogen atoms; R5 means hydrogen; R6 means (C1-C6)alkyl; (C6-C19)aryl or (5-15)-member heteroaryl containing nitrogen, oxygen or sulphur atoms as heteroatoms, wherein above aryl and heteroaryl are optionally substituted by one or more substitutes specified in a group consisting of halogen; (C1-C6)alkyl optionally substituted by 1-3 halogen atoms; and (C1-C6)alkoxy optionally substituted by one, two or three halogen atoms; R7 means hydrogen; R10 and R11, each independently mean (C1-C6)alkyl; or R10 and R11, together with N, whereto attached form a 3-8- member saturated or unsaturated ring optionally containing one or more O or S atoms, or one or more additional N atoms in the ring; k is equal to 0; m is equal to 1.
EFFECT: invention also refers to using the above compounds for preparing a drug for treating allergic and inflammatory diseases mediated by CRTH2 receptor activity, such as asthma, atopic dermatitis, allergic conjunctivitis, Churg-Strauss disease, sinusitits, basophilic leukaemia, and recurrent urticaria.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to biotechnology and immunology. The preparation contains an antibody, histidine and Polysorbate 80. Besides, a method of treating a subject with using the above preparation and a method of stabilising anti-human α-interferon antibody 13H5 are described. The invention can be used in medicine.
EFFECT: what is disclosed is a stable aqueous preparation containing the antibody or fragment thereof which are specifically bound to human α-interferon.
7 cl, 3 tbl, 2 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions refers to medicine, namely to paediatrics and may be used for preparing a drug or therapeutic nutritional composition for maturating an immune responses in a newborn infant. That is ensured by using an oligosaccharide specified in a group consisting of: lacto-N-tetrose, lacto-N-neotetrose, lacto-N-hexose, lacto-N-neohexose, para-lacto-N-hexose, para-lacto-N-neohexose, lacto-N-octose, lacto-N-neooctose, iso-lacto-N-octose, para-lacto-N-octose and lacto-N-decose. Also, the above oligosaccharide may be used for modulating the immune system of the newborn infant to ensure the developing beneficial intestinal microflora for the first weeks of life comparable to such found in breastfed infants.
EFFECT: group of inventions enables the developing beneficial intestinal microflora in the infant, and reduces the risk of a further allergy.
27 cl, 1 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to industrial microbiology, namely to creating of strain Lactobacillus plantarum specified in a group consisting of Lactobacillus plantarum 299, DSM 6595, Lactobacillus plantarum 299v, DSM 9843, Lactobacillus plantarum HEAL-9, DSM 15312, Lactobacillus plantarum HEAL-19, DSM 15313, and Lactobacillus plantarum HEAL-99, DSM 15316, for increasing the gastrointestinal bacterial diversity. The above strains are applicable to prevent developing low bacterial diversity (LBD) in a healthy individual, to prevent developing translocation, large intestinal bacterial overgrowth (LIBO) or small intestinal bacterial overgrowth (SIBO) in the individual with LBD, to prevent developing translocation in the individual with LIBO or SIBO.
EFFECT: using the above strains enables providing more effective prevention or treatment of gastrointestinal infections and a possibility to enlarge the bacterial diversity.
16 cl, 1 tbl, 1 dwg, 1 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to a preparation for babies for reduction or prevention of inflammation in a baby. The preparation for babies includes a source of protein, providing from 1 to 5 g of protein per 100 kkal of the preparation, a source of fat or lipids, providing from 3 to 7 g of fat or lipids per 100 kkal of the preparation, a source of carbohydrates, providing from 8 to 12 g of carbohydrates per 100 kkal of the preparation, a source of long-chain polyunsaturated fatty acids, including docosahexaenoic acid. The preparation also includes from 1×104 CFU to 1×1010 CFU of Bifidobacterium longum AH1206 NCIMB 41382 per a gram of the preparation. Also claimed are probiotic baby food and a method of reduction or prevention of inflammation in the baby or child with application of the said food.
EFFECT: invention ensures induction of anti-inflammatory response, makes it possible to reduce secretion of anti-inflammatory cytokines.
14 cl, 19 dwg, 2 tbl, 7 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to biotechnology and represents a method of producing a bacterial ghost preparation, a pharmaceutical composition, which is a vaccine or an adjuvant, a method of inactivating live bacterial cells in the bacterial ghost preparation and application of beta-propiolactone. The method includes obtaining the bacterial ghost preparation and processing the bacterial ghost preparation with beta-propiolactone in a final concentration from 0.01% to 1% (vol/vol), at which the quantity of live bacterial cells in the said ghost preparation reduces by at least 103-104. The pharmaceutical composition includes efficient quantity of the bacterial ghost preparation, processed with beta-propiolactone in a final concentration from 0.01% to 1% (vol/vol), and a pharmaceutically acceptable carrier, a diluent and/or an adjuvant.
EFFECT: claimed invention makes it possible to obtain the bacterial ghost preparation, which in fact does not contain live bacterial cells.
18 cl, 13 dwg, 7 ex
SUBSTANCE: 1 glass of an aqueous infusion of swallowwort herb or garden sage herb is orally administered daily on an empty stomach in the morning 1-2 hours before meals for 10 days. That is followed by administering an aqueous infusion of camomile blossom daily on an empty stomach for 10 days also. For the further 10 days, an aqueous infusion of plantain leaves is administered daily on an empty stomach; the infusions of chamomile blossom and plantain leaves are taken in a dose of 1/2 glass 3-5 times a day 30 minutes before meals. Administering the aqueous infusions is combined with orally daily administering an infusion of Saint-John's-wort for 30 days orally in a dose of 50 drops per 1/2 glass of water 3 times a day 30 minutes before meals. After that, the liquid biocomplex Normoflorin is orally administered 3 times a day daily for 4 weeks 30 minutes before meals in age doses. Normoflorin L is used for the first and second administration, and Normoflorin B - for the third one.
EFFECT: effective treatment ensured by Helicobacter pylori growth inhibition, antiseptic, anti-inflammatory herb action improving gastric mucosa trophism in a combination with the positive effect on the nervous system.
SUBSTANCE: group of inventions relates to field of biotechnology. Strain Bifidobacterium breve MCC 1274 FERM BP-11175 demonstrates low coefficient of conversion of linoleic acid into conjugated linoleic acid. Strain demonstrates coefficient of conversion of linoleic acid into conjugated linoleic acid not higher than 10%. To reduce or prevent obesity or to improve tolerance to glucose said strain is introduced in efficient quantity to subject requiring it. Also claimed are food product and drink, which contain preparation based on said strain.
EFFECT: strain is used to reduce or prevent obesity or improve tolerance to glucose as component of pharmaceutical composition or preparation.
22 cl, 4 dwg, 2 tbl, 7 ex
SUBSTANCE: method provides for cultivation at 37±1°C of strains of lactobacilli and bifidobacteria in the medium and packing of liquid product with account of daily dose necessary for patients. The medium contains components in the following quantities: caseine hydrolysate dissolved by distilled water, 0.33-0.4 g/l, sodium chloride 5 g/l, fructose 10 g/l, peptone 2 g/l, agar-agar 0.75 g/l for lactobacilli, for bifidobacteria - 1.0 g/l, ascorbic acid 0.25 g/l, distilled water 0.67-0.6 g/l. Strains-producers are Lactobacillus plantarum 8 RA-3, Lactobacillus fermentum 39, Lactobacillus fermentum 90 TC-4, Bifidobacterium bifidum 791, Bifidobacterium longum 379, Bifidobacterium bifidum 1. For lactobacilli and bifidobacteria they prepare accordingly media with different content of agar-agar, amine nitrogen in caseine hydrolysate 160-170 and 180-200 mg% and medium pH 7.8-8.0 and 8.5-8.6. Starting from the first generation the bifidobacteria and lactobacilli are cultivated for 24±1 hours, two strains together, one separately. The produced biomass is mixed with the fresh nutrient medium at the ratio of 1:1000, and strains of lactobacilli are cultivated 24±1 hours, strains of bifidobacteria - 48±1 hours. Upon completion of cultivation of biomass of strains they are mixed at the ratio of 2:1:2:1.
EFFECT: production of a product with high content of live microbial cells.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to application of probiotic bacterial strain for production of a probiotic composition for reducing sleep disorders and/or improvement of sleep quality in people and animals. As a bacterial strain used is Lactobacillus reuteri DSM 17938 or Bifidobacterium longum NCC 3001 (ATCC BAA-999).
EFFECT: invention ensures normalisation of sleep pattern in an individual by reduction of active sleep time, increase of slow sleep time and reduction of a number of awakening incidents.
14 cl, 2 dwg, 3 tbl, 4 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to versions of medication for reduction of halitosis, versions of compositions based on said medications and versions of application of said medications. Device for reduction of halitosis represents strains of microorganisms Lactobacillus acidophilus, selected from group Lactobacillus acidophilus DSM 19825, Lactobacillus acidophilus DSM 19826 and Lactobacillus acidophilus DSM 19827. Version of said medication represents culture supernatant of said strains. Also claimed are compositions, which contain said microorganisms, and their application for reduction of halitosis.
EFFECT: invention makes it possible to considerably reduce concentration of peptides in saliva, depleting in this way substrate, used by anaerobic microorganisms of oral cavity microflora, which are halitosis-causing agents.
10 cl, 7 dwg, 19 ex
SUBSTANCE: invention refers to medicine, particularly to paediatrics and neonatology, and can be used for treating small premature infants at the hospital stage of developmental care. A therapeutic complex comprises administering a probiotic preparation into the newborns. The preparation is presented with a liquid probiotic containing E.faecium L3 109 CFU in 1 ml. If the enteral nutrition volume of the newborn is 5 ml or more, this preparation is orally administered in a dose of 0.5 ml 3 times a day for 14 days.
EFFECT: method is effective in children with a very low body weight, promotes normalising the intestinal microflora and reducing a rate of manifestations of infectious complications.
2 ex, 3 dwg, 3 tbl
SUBSTANCE: invention refers to medicine and biotechnology, and represents a method for preparing a combined antibacterial preparation for treating acute intestinal infections. The invention is to prepare a biological ingredient biomass representing a complex of immunoglobulins or bifidus bacteria biomass, to mix it with an antibiotic substance in specified proportions, and differs from the known analogues by the fact that mixing the two ingredients of the preparation is preceded by grinding the biological ingredient only to be ground to the greatest maximum bulk density of the ground material.
EFFECT: invention improves the antibacterial activity of the combined preparation, which leads to reducing the length of treating an acute intestinal infection.
2 cl, 1 tbl, 3 ex
FIELD: biotechnology, microbiology, medicine.
SUBSTANCE: invention relates to the strain Lactobacillus paracasei CNCM I-2116 used for diarrhea prophylaxis causing by pathogenic microorganisms. Supernatant of this strain culture elicits ability to prevent colonization of intestine with pathogenic microorganisms causing diarrhea also and this strain is designated for preparing agent used for prophylaxis and/or treatment of disorders associated with diarrhea. Agent for oral administration represents therapeutically effective dose of the strain L. paracasei CNCM I-2116 or supernatant of its culture and acceptable foodstuff. Invention provides the enhanced viability of the strain in its applying and effectiveness in prophylaxis of adhesion to intestine cells and invasion to intestine cells of pathogenic microorganisms causing diarrhea.
EFFECT: valuable medicinal properties of strain.
5 cl, 8 dwg, 10 ex