Albumen tolerance induction
FIELD: food industry.
SUBSTANCE: invention is related to food industry and may be used for food allergy prevention. Hydrolysed by fermentative method egg whites with hydrolysis degree from 15% to 28% are applied in production of food compositions.
EFFECT: invention ensures tolerance to egg whites contained in food products with mammals.
5 cl, 5 dwg, 6 ex
The technical field
The present invention relates to the use of hydrolyzed proteins eggs to induce oral tolerance to intact proteins eggs in mammals, may be allergic to eggs.
Food allergies, of which the most common is allergic to cow's milk, caused in most cases, the response to dietary proteins. In the first years of life, the immune system is still in development and may not be able to recognize and be tolerant of such food proteins. The result is that the child or young animal refers to a food protein as a foreign substance and produces him an allergic reaction. Food allergies can affect not only people, but also other mammals, such as dogs and cats.
A Central role in adaptive immunity play a helper T-cells. The Th1 cells are essential for cell-mediated immune responses, whereas Th2 cells stimulate humoral immunity. Answers Th1 and Th2 are protivorechiyami, that is produced by cells of the Th1 cytokines inhibit the function of Th2 and Vice versa. It is shown that biased towards a Th2 immune response is crucial to ensure a successful pregnancy, but also about what prevails in childbirth and in the first months of life. Postnatal exposure to microbial antigens preferentially induces Th1 responses, which, as was expected, a counterbalance Th2-related cytokine production in newborns. In case of insufficient early microbial exposure the production of cytokines of the Th2-type (IL-4, IL-5 and IL-13) is continued further, leading to IgE production and consequently to allergic disease. However, it quickly became clear that this Th2-model is insufficient to explain the total immunopathology of allergic diseases, and recently it has been hypothesized that the initial stage of allergic diseases may be the result of erroneous activation of regulatory T cells (Treg), and not increased Th2 activity. Treg cells represent a small group of T cells capable of inducing immune tolerance. Describes several overlapping subsets of Treg cells (Th3, Tr1, CD4+, CD25+)expressing suppressor cytokines (IL-10, TGF-β).
The effect of oral tolerance is the ability with which the introduction of antigens through the mouth can prevent subsequent systemic immune responses to the same antigen presented in an immunogenic form. If the mechanism of oral tolerance does not develop properly or if there are disturbances in physiological SOS is the right of resistance to specific antigens this can lead to the development of hypersensitivity reactions. This mechanism can be explained as follows: after the first contact with the allergen responsible for the generation of IgE antibodies, which migrate to the surface of mast cells and basophils, where they bind with specific receptors. In repeated contact with the allergen surface IgE are cross-stitched on mast cells or basophils, which leads to cell activation and the release of chemical mediators, including histamine. This phenomenon leads to pathological effects, such as local or systemic vasodilatation.
Usually food Allergy appears only once susceptible baby, child or young animal for the first time faced with the new food. The first food proteins, which tend to have human babies, are at least cow's milk proteins and, as noted above, are allergic to cow's milk is the most common food allergies. It is generally accepted that infants with established Allergy to cow's milk have an increased risk of developing allergies to other food proteins, such as egg proteins and grains, but even in infants with successfully developed oral tolerance to cow milk proteins may later develop allergies to other foods is a diversified proteins, such as egg and corn protein, when administered in the diet during weaning.
From a dietary point of view, there are two methods of treatment developed allergies: must be either completely avoid foods containing the allergen or food products need to be processed to reduce their allergenic potential, for example, be subjected to hydrolysis. For this latter purpose are made of a mixture of baby food containing highly hydrolyzed cow's milk proteins (peptides consisting of no more than five amino acids).
However, there is a need for products that help to reduce the risk of developing allergies and stimulate the development of tolerance to intact proteins, especially in children who are considered at risk (for example, if the child has at least one suffering from allergies family member). For example, for induction in infants oral tolerance to cow milk proteins, it was suggested feeding partially gidrolizovannykh proteins of cow's milk. Fritsche and others (J. Allergy Clin. bnmunol, vol 100, No. 2, pages 266-273) using experimental animal models have shown that enzymatic hydrolysates of proteins of cow's milk with a degree of hydrolysis of 18% was able to induce oral tolerance to the intact proteins in cow's what about the milk, while hydrolysates with a degree of hydrolysis of 28% of this ability has not been demonstrated. The results of these experiments showed that prophylactic feeding rats a recipe with such moderately hydrolyzed cow's milk allergenicity which was reduced more than 100-fold compared to the standard formulation, inhibited the secretion of the fat cells of the intestine-specific IgE and mediator, both of which are factors in allergic reactions of immediate type. This work showed that cow's milk protein may determine the extent of enzymatic hydrolysis, which is supported by the ability of peptides to induce oral tolerance and at the same time their allergenicity significantly reduced.
Have been proposed and various other ways of improving the induction of oral tolerance to cow milk proteins, including the introduction of probiotics, as proposed in WO 2003/099037, or the introduction of compounds capable of increasing the activity of cyclooxygenase-2 (MOR-2), as proposed in WO 02/051437. However, induction of tolerance to other frequently causing allergic reactions food proteins, such as egg whites, was given relatively little attention. Actually, considering the fact that Allergy to cow milk proteins usually disappears spontaneously in aged TLD is up to five years, while Allergy to proteins of the egg disappears, usually slower and may even persist throughout life, this need may be even higher. Therefore, the aim of the present invention is providing a method of inducing oral tolerance to proteins of eggs.
Brief description of the invention
The present invention provides the use of hydrolyzed by enzymatic method proteins eggs with a degree of hydrolysis of from 15% to 28% in the manufacture of a composition for the induction of the mammalian oral tolerance to proteins of eggs.
The invention extends to a method of inducing oral tolerance to proteins of eggs by providing the needy in the mammal a composition containing a therapeutic amount of hydrolyzed proteins eggs with a degree of hydrolysis of from 15% to 28%.
Brief description of drawings
Figure 1 shows the residual OVA-specific antigenicity hydrolysates of egg.
Figure 2 shows the reduction of allergenicity in a functional study, stimulation of fat cells.
Figure 3 shows the ability of various protein hydrolysates eggs to suppress the response specific to the protein of eggs IgE.
Figure 4 shows the ability of various hydrolysates of egg to suppress the stimulation of fat cells of the intestine.
Figure 5 demonstrates the highly hydrolyzed egg whites are unable to suppress the response specific to the protein of eggs IgE or suppress the stimulation of fat cells of the intestine.
Detailed description of the invention
In this description, the following terms have the following meanings.
"Degree of hydrolysis" or "DH" of a protein refers to the amount of nitrogen in the unattached NH2-rpynnax divided by the total amount of nitrogen (NH - and NH2group), expressed as a percentage.
"Oral tolerance" means the active state of immunological hyporeactivity to antigens received oral route.
All references to percentages, unless otherwise represented by mass percentage.
Preferably the degree of hydrolysis ranges from 18% to 25%, more preferably from 23% to 25%.
For successful induction of oral tolerance to intact proteins eggs using hydrolyzed proteins eggs will require a balance between residual antigenicity hydrolyzed proteins and their ability to induce oral tolerance. In General, the residual antigenicity hydrolyzed protein should be at least 100 times lower than that of intact proteins.
According to the evaluation using the techniques described Fritsché and other (Int. Arch. Aller and Appi Imm., 93, 289-293, 1990), it is found that hydrolyzed egg whites with a degree of hydrolysis of from 20% to 28% have allergenicity is reduced compared to the intact proteins in eggs, at least 100 times.
Egg whites can be enzymatic Hydra is risovannymi using any suitable, known in this field. One example of a suitable method of hydrolysis is a two-step enzymatic hydrolysis of pasteurized egg mass from whole eggs. The egg mass for about 10 minutes, heated to a temperature in the range from 60 to 65°C., and then cooled to about 55°C. is Added protease, such as subtilisin bacterial serine of endoprotease (for example, offer for sale under the trade name Alcalase®), and the mixture is aged for at least two hours at a temperature of about 55°C to undergo partial hydrolysis. Then the temperature of the mixture rises to 70-75°C and maintained at this level for about 10 minutes. The mixture is again cooled to about 55°C and added to the next batch of enzyme. The mixture is kept at about 55°C for at least another two hours to achieve the desired degree of hydrolysis. Then the temperature rises to a value of from 85°C to 95°C and maintained at this level for a period of time up to 30 minutes for inaktivirovanie enzymes and termination of hydrolysis. The obtained hydrolyzed egg mass may, at the discretion be used either in this state or it can be subjected to spray drying to obtain a powdery product.
The composition is suitable for use in the present invention may be any food product, which traditionally includes whole eggs, with whole eggs is replaced gidrolizovannykh eggs that egg whites have a degree of hydrolysis of from 20% to 28%. Obtained by the method described above hydrolyzed egg powder may, for example, be used instead of whole egg powder in such recipes as desserts, baked English cream pie with custard, crème caramel. Alternatively, the hydrolyzed egg powder can divorce in water and used for the preparation of dishes such as omelets and scrambled eggs. Hydrolyzed egg powder is particularly suitable ingredient for foods intended for infants and young children, in particular for food products, suitable for use in the early stages of weaning baby from the breast. In addition, hydrolyzed egg powder can be used instead of egg powder, traditionally used for making such products.
As noted earlier, allergies to food proteins are not limited to people, and the method of the present invention can also be used to induce oral tolerance to proteins eggs in other mammals, in particular, animal companions such as dogs and cats. So, hydrolyzed egg whites with a degree of hydrolysis of from 15% to 28%may also be used as a substitute for whole eggs in food for animal companions, in particular, in food products, for example, recently stopped breastfeeding puppies and kittens.
Hereinafter the invention is described by the following examples.
Information, podtverjdayuschie the possibility of carrying out the invention
Preparation of egg white hydrolysates
The source material was pasteurized egg weight of whole eggs FT/OVO/0105 ABCD S.A., Avicole Bretonne Cecab Distribution (Ploermel, France).
30 kg egg mass of whole eggs was heated at 65°C for 10 minutes under stirring at a speed of 250 Rev/min After cooling to 55°C. was added 2% of enzymes Protamex® (party PW2A1006, NOVOZYMES A/S Bagsvaerd, Denmark) and the mixture was maintained at 55°C for 2 hours. After this first stage of hydrolysis was added 1% of enzyme Flavourzyme® 1000 L (party 400904, NOVOZYMES A/S Bagsvaerd, Denmark) and the mixture was heated for 10 min at 75°C. Then the mixture was cooled to 55°C., was added 1% of enzyme Flavourzyme and the mixture was maintained at 55°C for 2 hours. After this second stage of the hydrolysis mixture was heated for 30 minutes at 90°C and then was spray dried to obtain a hydrolyzed egg white powder, which was preserved in supporting the fresh condition of the product aluminum foil package.
35 kg egg mass of whole eggs was heated at 65°is within 10 minutes under stirring at a speed of 250 rpm After cooling to 55°C was added 5% enzymes Protamex® (party PW2A1006, NOVOZYMES A/S Bagsvaerd, Denmark) and the mixture was maintained at 55°C for 2 hours. After this first stage of hydrolysis was added 1% of enzyme Flavourzyme® 1000 L (party 400904, NOVOZYMES A/S Bagsvaerd, Denmark) and the mixture was heated for 10 min at 75°C. Then the mixture was cooled to 55°C, then added another 4% enzyme Flavourzyme and the mixture was maintained at 55°C for 2 hours. After this second stage of the hydrolysis mixture was heated for 30 minutes at 90°C and then was spray dried to obtain a hydrolyzed egg white powder, which was preserved in supporting the fresh condition of the product aluminum foil package.
30 kg egg mass of whole eggs was heated at 65°C for 10 minutes under stirring at a speed of 250 Rev/min After cooling to 55°C. was added 10% enzymes Alcalase®2.4L (party 500357, NOVOZYMES A/S Bagsvaerd, Denmark) and the mixture was maintained at 55°C for 2 hours. After this first stage of the hydrolysis mixture was heated for 10 min at 75°C. Then the mixture was cooled to 55°C, after which it was added 10% enzymes Alcalase and the mixture was maintained at 55°C for 2 hours. After this second stage of the hydrolysis mixture was heated for 30 minutes at 90°C and then was spray dried to obtain a hydrolyzed egg powder is a, who persisted in supporting the fresh condition of the product aluminum foil package.
Products containing gidrolizovannogo whole eggs
Example ingredients for sweet egg pudding, containing hydrolyzed egg, is as follows:
|Whole milk (fat content of 3.5%)||62,0|
|Free from allergenic substances egg powder||2,5|
This pudding can be prepared by any known in this field the appropriate way.
Example ingredients for spicy egg pudding, containing hydrolyzed egg, is as follows:
|Whole milk (fat content of 3.5%)||62,0|
|Frozen carrot cubes||10,0|
|Free from allergenic substances egg powder||1,5|
This pudding can be prepared by any known in this field the appropriate way.
Example ingredients for egg pasta, containing hydrolyzed egg, is as follows:
|Cereals durum wheat||70,6|
|Free from allergenic substances egg powder||5,9|
Such pasta can be prepared by any known in this area as suitable methods for the om.
Residual antigenicity egg hydrolysates
The residual antigenicity of egg white albumin (OVA) in hydrolysates of examples 1, 2 and 3 was determined by inhibition with polyclonal rabbit anticorodal with antibodies to OVA protein using enzyme-linked immunosorbent assay (ELISA). In wells tablet for micrometrology was added 100 μl of OVA solution with a concentration of 50 μg/ml in carbonate-bicarbonate buffer and was maintained for 24 hours at 4°C. the Tablets were washed four times PBS-Tween buffer and free sites were blocked by adding to each well 200 μl of fish gelatin (0.5% in PBS-Tween). Tablets was maintained for 1 hour at room temperature (RT) and again 4 times were washed in PBS-Tween.
In a separate test tubes for 1 hour at room temperature were treated with 1 part of standard drug OVA or sample for testing with 1 part of the rabbit antibodies to OVA protein (dilution 1:20000). After incubation, 100 µl of this inhibitory mixture was added to the above-mentioned coated and blocked wells and was aged for 2 hours at room temperature. The tablets were washed four times in PBS-Tween. Then was added goat anti-rabbit peroxidase labeled conjugate (0.1 ml of a solution with a dilution 1:2000), the tablets were stored for 1 hour at room temperature and were washed 4 times in PBS-Tween. Added Chromogen is initial substrate (0.1 ml o-phenylenediamine). After incubation for 15 minutes using a multichannel ELISA spectrophotometer was determined by optical density at 492 nm.
The results are shown in figure 1, which shows that OVA-specific antigenicity of hydrolysates of examples 1-3 as compared with intact protein eggs was reduced by more than 10,000 times.
The residual allergenicity of egg hydrolysates
For determination of IgE-dependent allergic reactions to antigenic molecules (OVA) was performed in vitro functional study selection labeled with tritium serotonin from sensitized mast cells in rats according to a previously described in the literature (Fritsche and other J. Allergy Clin. Immunol, No. 2, vol 100, str-273). In short, the fat cells were obtained from normal rats Sprague-Dole peritoneal washings in the modified Dulbecco environment Needle containing 10% fetal calf serum. Cells were washed in this environment and was kept over night at 4°C. After two washes in phosphate-NERE-fish-gelatin buffer (PHG) with pH 7.0 cell re-suspendibility in the same buffer at a concentration of 5×105cells in 1 ml and was diluted with one volume of rich IgE antibodies to OVA rat serum containing 5 µci/ml3H-serotonin. After incubation for 2 hours at 37°C. the cells then were washed three times in PHG and re-suspendibility in PH at a concentration of 2.5×10 5cells in 1 ml of Sensitized mast cells were distributed on tablets for micrometrology (0.1 ml in each well) and was mixed with 0.05 ml of a serial dilution hydrolyzed proteins eggs, obtained according to example 2 (1/10 ranging from 10 mg/ml). The mixture was maintained for 60 minutes at 37°C and centrifugals. An aliquot (0.05 ml) of the supernatant was mixed with 2 ml of scintillation fluid and using a β counter-radiation Packard company measured the emission of3N.
The results are shown in figure 2, which shows that hydrolyzed egg had greatly reduced allergenicity (25 μg OVA/g protein equivalents) and that this low value was lost when the inclusion of hydrolyzed eggs dessert-type pie with fruit.
Induction of oral tolerance to proteins of eggs by feeding protein hydrolysate eggs
Was investigated in vivo the ability to inducyrovannuu oral tolerance to egg products using rats as model objects. Six groups of rats Sprague-doli (6 animals per group)contained in not containing the protein of the egg diet for 1 to day 19 of the experiment were given ad libitum different experimental liquid egg whites/egg white hydrolysates or water (control), placed in their waterers, and a solid diet in the form not containing the protein of eggs granules. Animals Yes is Alice the following products:
Group a: whole egg powder (20 g/l);
Group: hydrolyzed egg powder from example 3 (120 g/l), DH 25%;
Group: hydrolyzed egg powder from example 2 (120 g/l), DH 23%;
Group D: hydrolyzed egg powder from example 1 (120 g/l), DH 20%;
Group E: subjected to ultrafiltration hydrolyzed egg powder from example 3(120 g/l), DH 31%;.
Group F: H2O (control).
Given the group subjected to ultrafiltration hydrolyzed egg powder was obtained in the following way. The substrate obtained in example 3, hydrolyzed egg mass was subjected to microfiltration using a filtration module Sefiltec FBF 0102 bag filter 100 μm (PGF 51 F 02). After this stage microfiltration filtrate was subjected to ultrafiltration using self-made ultrafiltration module with membranes 4000 daltons (ES404, PES, 4000 MWCO production PCI Membrane Systems). Then the filtrate was subjected to freeze-drying.
Total nitrogen in the hydrolysates was determined by the Dumas method (method Carlo Erba). The degree of hydrolysis was measured by the TNBS method according AdIer-Nissen J. Agric. Food. Chem. 1979 27: 1256-1262).
All rats were immunotherapies 5 day experiment subcutaneous injection of 0.1 mg of egg albumin +0.2 ml 3% Al(Oh)3. 19 day, all animals were euthanized. Blood was produced and serum was analyzed nespetsificheskie IgE-antibodies (antialbumin) previously described in the literature (Fritsche R, Bonzon, M. hit Arch Allergy Appi Immunol 1990; 93: 289-93) by ELISA. In short, the tablet microtitration covered OVA for 24 hours at 4°C. the Tablets were washed PBS Tween 20 and within 1 hour blocked fish gelatin. After adding a serial dilution of test serum (1/2) and incubation for 2 hours was added sheep anticavity to IgE rats. After incubation for 1 hour at room temperature was added a second peroxidase labeled antibody, followed by 1 hour was added to the substrate (o-phenylenediamine). The optical density at 492 nm diluted 1:5 pooled normal rat serum was considered as nonspecific background. The concentration of specific antibodies was expressed as the maximum dilution of the test serum in excess of this value.
Protease fat cells of the rat (RMCPII) is released into the bloodstream after IgE-mediated stimulation of fat cells of the intestine. Oral stimulus, leading to selection of RMCPII, is the criterion of IgE-sensitization or tolerization at the level of the fat cells of the intestine. Levels of RMCPII was determined using a commercially available ELISA kit (Moredun Animal Health Ltd., Edinburgh, Scotland), based on the principle of sandwich-analysis, which is the process of coating tablets monoclonal antibody to RMCPII, after which is added investigated serum and the second is Vecie polyclonal antibody to RMCPII, conjugated with horseradish peroxidase.
The results are presented in figures 3, 4 and 5. From figure 3 it can be seen that protein hydrolysates eggs from examples 1-3 are able to suppress the response specific to the protein of eggs IgE when feeding their animals for 19 days ad libitum compared with metalizowanej control Group (F), which were induced high levels of IgE antibodies against the proteins of eggs. More precisely, the levels of IgE antibodies to OVA (expressed as logarithm of the antibody titer) were as follows: group a: 4+/-1,1; Group b: 4,1+/-0,9; Group C: 3.3V+/-1,1; Group D: 4,1+/-2,0; Group F: 6,1+/-0,3. When comparing groups shows a significant difference (p<0.05) of groups A-D from F group (control).
Figure 4 also shows that stimulation of mast cells of the intestine is suppressed in groups a, b, C and D, but not in Group F (control). Indicators values RMCPII expressed in μg/ml are as follows: group a: 0+/0,0; Group b: 0,6+/-1,0; Group: 1,2+/-1,7; Group D: 0,6+/-0,8; Group F: 2,8+/a-0.7. When comparing groups shows a significant difference (p<0.05) of groups A-D from F group (control).
Figure 5 shows that the fed Group E strongly hydrolyzed egg whites not induced oral tolerance to OVA that was assessed by the suppression of the response specific to the protein of eggs IgE or to suppress stimulation of fat cells of the intestine.
Levels of RMCPII and IgE antibodies to OVA not differ from values, receiving the data for the control group.
1. The use of hydrolyzed by enzymatic method proteins eggs with a degree of hydrolysis of from 15% to 28% in the manufacture of a composition for the induction of the mammalian oral tolerance to proteins of eggs.
2. The use according to claim 1, in which the mammal is a human.
3. The use according to claim 2, in which the composition is a food product to excommunicate from the breast children.
4. The use according to claim 1, in which the mammal is a domestic animal such as a cat or a dog.
5. The use according to any one of the preceding paragraphs, wherein the degree of hydrolysis ranges from 23% to 25%.
SUBSTANCE: described are novel diaminotriazole compounds of general formula
(values of radicals are given in the claim), pharmaceutically acceptable salts thereof, a pharmaceutical composition containing said compounds, a method of inhibiting JAK2 and JAK3 kinase activity and use of the novel compounds to produce a medicinal agent for treating several diseases.
EFFECT: high efficiency of the compounds.
19 cl, 3 tbl, 26 ex
SUBSTANCE: the invention relates to medicine and pharmaceutics, in particular, to creation of pharmaceutical composition in the form of suspension with anti-shock and anti-allergic action. The pharmaceutical composition with said actions contains dexamethasone sodium phosphate and “Micellate of calcium carbonate and magnesium”. The pharmaceutical compositions also contain sodium hyalurate, alcohol, Nipagin, fructose and water. A variant of the invention is a suspension which additionally contains sodium fluoride and ascorbic acid. Research was carried out and it proved that the offered pharmaceutical compositions have expressed specific pharmacological effect, they express anti-shock action, and have no toxic effect with various doses and various routes for experimental animals. The compositions have no irritant effect, sensibilizing action was not expressed.
EFFECT: the offered pharmaceutical compositions are effective and safe medication and can be used to treat state of shock, suitable for treatment of patients additionally suffering from diabetes mellitus.
2 cl, 2 ex, 1 tbl, 3 dwg
SUBSTANCE: invention relates to novel diarylamine-containing compounds of formula (I) or formula (4b), pharmaceutically acceptable salts thereof, which have c-kit inhibiting properties. In formulae (I) and (4b), each R1 independently denotes H, -C(O)OH and -L1-C1-6alkyl, where L1 denotes -O- or -C(O)O-, or any two neighbouring R1 groups can together form a 5-6-member heterocyclic ring containing a nitrogen atom or an oxygen atom as a heteroatom, a 6-member heterocyclic ring with one or two nitrogen atom s as heteroatoms, optionally substituted with a C1-4alkyl, and R5 denotes hydrogen or C1-C6alkyl; values of radicals Ar and Q are given in the claim. The invention also relates to a pharmaceutical composition containing said compounds, and a method of treating diseases whose development is promoted by c-kit receptor activity.
EFFECT: more effective use of the compounds.
17 cl, 3 tbl, 9 ex
FIELD: food industry.
SUBSTANCE: invention relates to a non-allergenic food product. The food product includes an amino acid fraction containing at least one component chosen from the group consisting of amino acids and peptides with a degree of polymerisation 7 or less, and a lipid fraction containing at least one fatty acid chosen from the group consisting of arachidonic acid and docosahexanoic acid. The composition content of protein and other peptides with molecular weight 1000 daltons or more (in relation to dry weight) is less than 0.01 wt %, preferably - no less than 0.001 wt %, more preferably - no less than 0.0001 wt %. The food product is used for allergy diagnostics.
EFFECT: invention allows to produce a product which does not impart allergic reactions and is able to attenuate intensity of the patients' allergic reactions.
7 cl, 4 ex
SUBSTANCE: invention provides an IFA test system for detection of specific staphylococcus IgE-antibodies in blood serum of a patient with allergic diseases, hypersensitive to staphylococcus allergens; a method for detection of specific staphylococcus IgE-antibodies in blood serum of the patient with allergic diseases, hypersensitive to staphylococcus allergens, with using said test system; and a diagnostic technique for staphylococcus allergy.
EFFECT: application of the declared invention allows detecting staphylococcus allergy.
12 cl, 4 ex, 2 tbl, 1 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to compound, represented by the following formula (I), where R represents hydrogen atom or P(=O)(OH)2, X represents oxygen atom or sulphur atom, Y represents CH2CH2 or CH=CH, R1 represents trifluoromethyl, difluoromethyl or cyano, R2 represents alkyl, which has 1-4 carbon atoms, and optionally substituted with hydroxyl group (groups) or halogen atom (atoms), R3 and R4 can be similar or different, and each represents hydrogen atom or alkyl, which has 1-4 carbon atoms, and n=5-8, or its pharmaceutically acceptable acid-additive salt. Invention also relates to 2-amino-2-[2-(4-heptyloxy-3-trifluoromethylphenyl)ethyl]propan-1,3-diol or its hydrochloride and pharmaceutical composition, containing said compounds.
EFFECT: elaboration of pharmaceutical composition, applied for treatment or prevention of autoimmune diseases, prevention or suppression of resistance or acute rejection or chronic rejection of organ or tissue transplant; treatment or prevention of graft-versus-host disease (GvH) resulting from transplantation of bone marrow; or treatment or prevention of allergic diseases.
16 cl, 39 ex
SUBSTANCE: disclosed compounds can be used as an antipruritic agent in case of atopic disease such as atopic dermatitis when a steroid medicinal agent is ineffective. In formula R is C1-6 alkoxy, optionally substituted methyoxy, or an amine which is monosubstituted with C1-6 alkyl, where the R-C(=O)- group is bonded in the meta or para-position.
EFFECT: high efficiency of using said compounds.
21 cl, 16 dwg, 4 tbl, 30 ex
SUBSTANCE: invention refers to application of enterovirus in preparing a pharmaceutical composition for prevention or treatment of the diseases associated with IgE-mediated allergic sensitisation and related diseases with using an enteroviral vaccine in which enterovirus does not contain an exogenous nucleotide sequence integrated into a viral genome and coding an allergen causing said allergic sensitisation, and also to a method for prevention or treatment of said diseases.
EFFECT: effective products for treating said diseases.
10 cl, 3 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: nutritional and pharmaceutical composition in form of baby food contains fat, protein and carbohydrate components and includes milk serum and casein with weight ratio of casein to serum from 1:1 to 1:2.4. They contain, at least: 3 g of arginine per 100 g of protein, from total content of fatty acids: 10 wt % of linoleic acid, 1 wt % of alpha-linoleic acid, one long-chain polyunsaturated fatty acid, selected from group, consisting of docosahexaenic, arachidonic and eicosapentaenoic acid, to 25 wt %, at least one polyunsaturated fatty acid and 2-12 g of indigestible oligosaccharides with polymerisation degree from 2 to 100 per 100 g of dry weight of said composition, as well as neutral and acidic oligosaccharides, containing units of uronic acid. Pharmaceutical composition is applied in treatment and/or prophylaxis of inflammatory disease, diarrhea, eczema and/or atopic dermatitis. Prevention of allergy or diarrhea is performed by introduction of composition to child enterally or perorally.
EFFECT: inventions ensure stimulation of immune system maturing and development in babies of intestine and intestinal flora, similar to flora, obtained during breast feeding, optimal feeding, prevents penetration of allergens into general blood circulation and reduces risks associated with feeding with baby's formula based on milk serum.
17 cl, 4 tbl, 3 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions relates to medicine and can be applied for treatment of hyperaemia and edema of mucous membrane of upper airways. For this purpose introduced is loratadine or proper quantity in form of its acceptable salt in combination with phenylephrine or as monomedication. Loratadine is introduced in regimen 2.5 mg four times per day, and phenylephrine is introduced in regimen 8-10 mg four times per day. Loradadine introduction in regimen 2.5 mg per day makes it possible to reach high efficiency of treatment in absence of side reactions.
EFFECT: treatment efficiency by loratadine in combination with phenylephrine in claimed regimen is conditioned by their synergetic effect as well as in absence of side reactions.
28 cl, 3 tbl, 1 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to field of pharmaceutics. Composition contains botulinum toxin, polysorbate 20 and methionine, where methionine is present in amount from 25 to 75 mM, and polysorbate 20 is present in amount from 0.1 to 2.5 mg/ml.
EFFECT: composition possesses improved stability; application of liquid pharmaceutical composition in form of combination of polysorbate 20 and methionine as botulinum toxin stabilisers instead of proteins of animal origin albumin and gelatin eliminates risk of organism contamination by pathogens or microorganisms of serum origin and makes it possible to introduce into organism safely; in addition, composition is convenient for application in direct introduction to patients.
8 cl, 8 tbl
SUBSTANCE: group of inventions relates to medicine, namely to resuscitation science and intensive therapy, and can be used for providing feeding of critically ill patients or patients exposed to stress. For this purpose first nourishing preparation with specified composition is introduced to patient in SIRS phase, and in phase CARS second nourishing preparation of specified composition is introduced.
EFFECT: application of claimed inventions reduces risk of infection and body weight loss increasing probability of recovery due to reduction of oxidative stress and muscle decomposition.
SUBSTANCE: invention represents application of composition, which includes protein material, where said protein material provides, at least, 24% of energy value of composition (en.%) and, at least, 12 wt % of all protein material is represented by leucine, for preparation of medication for treatment of subject with obesity.
EFFECT: extension of assortment of compositions, efficient for treatment of obesity.
SUBSTANCE: invention refers to pharmaceutical industry, particularly to ointment for treating burn diseases. The ointment for treating burn diseases, containing as an active substance, dry albumin and ethanolic propolis extract, and as an ointment base, salve base, penthol and purified water in a certain ratio of components.
EFFECT: ointment exhibits reparative, antiinflammatory, dehydrating, necrolitic and antimicrobic action and is effective for treating burn diseases.
FIELD: medicine; veterinary science.
SUBSTANCE: method provides inoculation and incubation of spore culture Bacillus subtilis 3 in a nutrient medium containing placental embryonic utricular hydrolyzate of animals' tissues and organs containing 90 mg % amine nitrogen and prepared from placenta, embryos and uterus of butchers to produce a culture fluid of culture Bacillus subtilis 3. Then montmorillonite fraction of zeolite is produced by conditioning in hydrochloric acid followed by removal of soluble salts and quartz with distilled water. There are remained zeolite particles of size 0.0006-0.0009 mm. Then the fraction is dried. After that, suspending montmorillonite fraction of zeolite and milk albumin hydrolyzate are added to the culture fluid Bacillus subtilis 3. The culture fluid Bacillus subtilis 3, suspending fraction of zeolite, and milk albumin hydrolyzate are mixed in the ratio 1:1:0.5 respectively. The produced preparation is sterilised and introduced once in doses 7-10 cm3 (to small animals) and 15-20 cm3 (to large animals) at 6.5-7.5 mg of solid per 1 kg of live weight within first postradiation 1-10 days.
EFFECT: higher protective effectiveness from radiation injuries and reduced application time.
3 cl, 1 tbl, 7 ex
SUBSTANCE: there is offered application of the substance representing enzyme-processed fish protein hydrolyzate able to inhibit activity of acyl-CoA cholesterole acyltransferase and to intensify mitochondrial β-oxidation for making a pharmaceutical or food composition applied for treatment and/or prevention of hepatic adipose degeneration in animals, for treatment and/or prevention of hypercholesterolemia and for treatment and/or prevention of hyperhomocysteinemia, and also for treatment and/or prevention of atherosclerosis, coronary heart disease, stenosis, thrombosis, myocardial infarction and stroke in an animal. There is offered method for making enzyme-processed fish protein hydrolyzate able to inhibit activity of acyl-CoA cholesterole acyltransferase, to reduce triglyceride concentration in liver, to reduce homocysteine concentration in plasma and/or to intensify mitochondrial β-oxidation. The preferential embodiment of the invention concerns FPH application as an antiatherogenic and cardioprotective agent presented either as a pharmaceutical agent, or as a functional food.
EFFECT: improved properties of the substance.
14 cl, 7 ex, 5 tbl, 4 dwg
SUBSTANCE: invention is related to medicine, namely, to orthopaedic stomatology and may be used in treatment of inflammatory diseases of mouth tunica mucosa in area of dentures and/or implants. For this purpose affected section of tunica mucosa is coated with argacol of 0.3-0.6 mm layer. Treatment is carried out 2-3 times per day for 5-14 days.
EFFECT: application of argacol in specified mode makes it possible to provide for high treatment effect with no unpleasant feelings of patient.
2 cl, 2 ex
FIELD: food products.
SUBSTANCE: invention relates to compositions and food products made of oat fractions. Compositions includes at least 25 wt % of protein and at least 1 wt % of emulsifying lipids as water-insoluble mixture and not more than 8 wt % of β-yeast cellulose on dry weight basis count. Protein and emulsifying lipids are obtained of the same oat fraction. Mass ratio protein and emulsifying lipids makes from 1: 0.01 to 1: 0.6. Compositions includes at least 15 wt % of protein hydrolizate and at least 1 wt % of emulsifying lipids as water-insoluble mixture. Protein and emulsifying lipids are obtained of the same oat fraction which is hydrolised. Mass ratio of protein hydrolizate and lipids is from 1:0.01 to 1:1. Food product includes at least one main nutritious element and composition. Also method of obtaining mentioned compositions is shown.
EFFECT: improvement of wheyey lipidic profile.
2 tbl, 16 ex
FIELD: medicine, cosmetology.
SUBSTANCE: cosmetic composition contains complex of active agents (A) having active agent (A1), which is selected from sericine and/or sericine hydrolysates and/or their derivatives and/or their mixtures, and active agent (A2), which is selected from fibroin and/or its hydrolysates and/or its derivatives and/or its mixtures, note that the ratio of active agents (A1):(A2) ranges from 10:90 to 70:30. Two-component agent for colouring keratic fibers consists of the first component (K1) containing at least one preproduct of colour (FV), and the second component (K2) containing at least one complex of active agents (A) consisting of active agent (A1), which is selected from sericine and/or sericine hydrolysates and/or their derivatives and/or their mixtures, and active agent (A2), which is selected from fibroin and/or its hydrolysates and/or its derivatives and/or its mixtures, note that the ratio of active agents (A1):(A2) ranges from 10:90 to 70:30 and at least one of the components contains at least one amphiprotic polymer (AP). Three-component agent for colouring of keratic fibers contains additional third component (K3) containing at least one oxidising component. Method of colouring of keratic fibers comprises applying one of the components over fibers, thereafter, it is kept for the time of reaction and washed out. One of the agents is used for cleaning and/or treating of skin and hair or for restructuring of keratic fibers, precisely human hair. Method of skin and hair treating comprises applying one of the agents to skin or hair, note that it is washed our after the time of reaction from 1 to 45 minutes.
EFFECT: increase of efficacy for the cosmetic agents.
18 cl, 4 tbl, 22 ex
SUBSTANCE: invention can be used for stimulation of the immune function in emotional-pain stress. For this purpose, the parenteral administration of amino acid L-lysine is used in rats with doses of 0.5, 1.5, 5, 15, 50, 150, 450 mcg/kg, once a day, with course of 4 days, 15 min before stressful exposure.
EFFECT: invention enables prevention of stress-induced immunosupression.
FIELD: biotechnology, biochemistry.
SUBSTANCE: invention relates to producing the biologically active complex eliciting antioxidant and immunomodulating activity and used in medicine, cosmetics, veterinary science and food industry. The biologically active complex preparing by enzymatic hydrolysis of muscle tissue represents complex of biologically active compounds involving carnosine and anserine in the amount 85-97 wt.-% of the native content of these components in poultry muscle tissue, 1-7 weight parts of amino acids, 0.5-12 weight parts of oligopeptides of molecular mass 10 kDa, not above, and 0.1-15 weight parts of cyclic and polycyclic phenolic compounds as measured for 1 weight part of carnosine and anserine in the complex. This complex is prepared by enzymatic hydrolysis of milled and homogenized water muscle tissue in preferable dilution homogenate with water in the range 0.2-0.6 and with using proteolytic enzymes in the amount 2-5 wt.-% of the protein content and working at pH 4.5-8.5 and at enhanced temperature being preferably at 45-65°C. Product is isolated as extract or powder prepared in drying the extract. Invention provides enhancing effectiveness of the claimed complex.
EFFECT: improved method for preparing, valuable properties of complex.
7 cl, 6 tbl, 6 ex