Method for prevention of using corticosteroids

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

 

The scope of the invention

The present invention relates to the use of the nutritional composition to prevent the introduction of corticosteroids, particularly in infants and young children.

Prior art

Skin diseases such as eczema, infantile eczema, atopic dermatitis, dermatitis herpetiformis, contact dermatitis, subarray dermatitis, neurodermitis, psoriasis and intertrigo, pose a significant problem. For the treatment of skin diseases such people applied corticosteroids. However, the use of corticosteroids has important disadvantages, because they can cause caused by steroid side effects. Some caused by steroids side effects are skin changes, such as blanching of the skin resulting in a sharp narrowing of the blood vessels, hypopigmentation, reactive worsening of pre-existing skin condition, prickly heat, acne rosacea, perioral dermatitis, acne, skin atrophy with telangiectasia, star pseudochromis, purpura, skin strips, delayed wound healing, hypertrichosis of the face; or skin infections.

Bukutu et al. (Pediatr. Rev. 2007; 28(12); e87-e94) reported that the use of Chinese herbal medical broth has reduced the use of topical corticosteroids. Passeron et al. (Allergy 2006:61:431-437) described the study, is that Lactobacillus rhamnosus Lcr35 plus prebiotic preparation obtained from the fermentation broth for L. rhamnosus Lcr35, gave the children two or more years and noted that the use of drugs for local treatment significantly decreased at the end of the study.

Document WO 2004069156 refers to preparative forms containing inactivated probiotic bacteria, and to methods of using these preparative forms.

Document WO 2005039597 relates to a method of stimulating the immune system and the treatment and/or prevention associated with immune system disorders in mammals, particularly newborns, including the introduction of acidic and neutral oligosaccharide oligosaccharide. There are also food composition suitable for use in such methods.

A brief description of the invention

In a double-blind placebo-controlled study on 1000 infants and small children, it was found that the introduction of certain probiotics reduced the use of corticosteroids and other dermatological preparations. In the control group, the use of corticosteroids and dermatological preparations was observed in 40 infants and young children, while only 16 children from the group of prebiotics were used corticosteroids and dermatological preparations. Consequently, the authors found that the introduction of galactooligosaccharides, fructooligosaccharides is, the uronic acid oligosaccharide, or a combination effectively reduces the use of corticosteroids.

A detailed description of the preferred embodiments

The present invention relates to a method of preventing local application of corticosteroids and/or prevent the introduction of inhibitor calcineurin, and this method includes the introduction of a composition containing at least one nevereverever saccharide selected from the group consisting of galactooligosaccharide, fructooligosaccharide, uronic acid oligosaccharide.

The invention also relates to the use of a composition containing at least one nevereverever saccharide selected from the group consisting of galactooligosaccharide, fructooligosaccharide, uronic acid oligosaccharide, upon receipt of a composition to prevent the local application of corticosteroids and/or prevent the introduction of inhibitor calcineurin. In other words, the invention relates to at least one nevereverever the saccharide selected from the group consisting of galactooligosaccharide, fructooligosaccharide, uronic acid oligosaccharide, to prevent local application of corticosteroids and/or prevent the introduction of inhibitor calcineurin. The invention also relates to a method for producing a composition for p is edatrexate local application of corticosteroids and/or prevent the introduction of inhibitor calcineurin, moreover, this method includes the introduction of a specified composition at least one neperebrodivsego of saccharide selected from the group consisting of galactooligosaccharide, fructooligosaccharide, uronic acid oligosaccharide.

In the context of the present invention, prevention of local application of corticosteroids means that compared with the control group, fewer individuals require local application of corticosteroids for the treatment of skin diseases such as eczema, infantile eczema, atopic dermatitis, dermatitis herpetiformis, contact dermatitis, subarray dermatitis, neurodermitis, psoriasis and intertrigo. Thus, in one aspect, the present invention, preferably, in infants and young children, reduces the risk of side effects of corticosteroids, such as, for example, blanching of the skin resulting in a sharp narrowing of the blood vessels, hypopigmentation, reactive worsening of pre-existing skin condition, prickly heat, acne rosacea, perioral dermatitis, acne, skin atrophy with telangiectasia, star pseudochromis, purpura, skin strips, delayed wound healing, hypertrichosis of the face; or a skin infection. Also, in the context of the present invention prevent the introduction of inhibitor calcineurin usually means that, compared to con the roll group, fewer individuals require the introduction of inhibitor calcineurin as an alternative to corticosteroids for the treatment of skin diseases. Normally, therefore, the present invention, preferably, in infants, reduces the risk of side effects of inhibitor calcineurin. In essence, the present invention may be considered non-therapeutic.

Nevereverever oligosaccharides

The present composition preferably contains at least one nevereverever saccharide selected from the group consisting of galactooligosaccharides, fructo-oligosaccharides and uronic acid oligosaccharides.

Used in the present invention, the term "oligosaccharide" preferably refers to a saccharide with a degree of polymerization (DP) from 2 to 250, preferably a DP of 2 to 100, preferably from 2 to 60. It is clear that in the context of the present invention, the saccharide with DP in a certain range can include a mixture of sugars with different mean values of the DP, for example, if the oligosaccharide with a DP of 2 to 100 included in the present composition, it may include compositions that contain oligosaccharides with a DP of 2 to 5, DP from 50 to 70 and DP from 7 to 60.

Used in the present invention, the term "nevereverever oligosaccharide" refers to oligosaccharides, which namerevayutsya or merely an hour is ichno digested in the intestine by the action of acids or digestive enzymes present in the upper gastrointestinal tract of man (small intestine and stomach), but which mix the intestinal flora of man. For example, sucrose, lactose, maltose and maltodextrins are considered digestible. For example, galactooligosaccharide, fructo-oligosaccharides and uronic acid oligosaccharides are neperevershenymy the oligosaccharides.

The present composition preferably contains fructooligosaccharide. Used in the present invention, the term "fructooligosaccharide" refers to nevereverever the oligosaccharide containing a chain connected at least 2V units procosi, with a DP of 2 to 250, preferably from 7 to 100, preferably from 20 to 60. Preferably, the inulin is used. Inulin, for example, available under the trade name "Raftilin HP®", (Orafti). The average DP of the present fructooligosaccharide is preferably at least 7, preferably at least 10, preferably below 100. Used fructooligosaccharide preferably has (most) of fructose units linked by the relationship in(2─►1). Other terms that mean fructo-oligosaccharides include inulin, fructooligosaccharide, polymaltose, fructans and oligofructose. The present composition preferably contains fructooligosaccharide with DP from 2 to 200.

The present composition preferably stereotactical. Used in the present invention, the term "galactooligosaccharide" refers to nevereverever the oligosaccharide in which at least 30% sharidny units are galactose units, preferably at least 50%, preferably at least 60%. The present composition preferably contains galactooligosaccharide with a DP of 2 to 100, preferably a DP of 2 to 10. Preferably, the sugars of galactooligosaccharide are linked. Therefore, preferably the present composition comprises beta-galactooligosaccharide. In a particularly preferred embodiment, the present composition contains transplantological ([galactose]n-glucose; where n is an integer from 1 to 60, i.e. the, 2, 3, 4, 5, 6, ...., 59, 60; preferably, n=2, 3, 4, 5, 6, 7, 8, 9 and/or 10). Transplantological (TOS) are sold, for example, under the trademark Vivinal™ (Borculo Domo Ingredients, Netherlands).

The present composition preferably contains galactooligosaccharide and fructo-oligosaccharides preferably, transplantological with DP from 2 to 7 and fructo-oligosaccharides with a DP of 10 to 100.

The present composition preferably contains uronic acid oligosaccharide. Used in the present invention, the term "oligosaccharide uronic acid" refers to an oligosaccharide, preferably where at least 25%, predpochtitelno, at least 50% of the monosaccharide units present in the oligosaccharide represent an oligosaccharide selected from the group consisting of glucuronic acid, mannurone acid, iduronovoy acid, Rybarikova acid, galacturonic acid and glucuronic acid. In a preferred embodiment, the uronic acid oligosaccharide contains at least 50% of the galacturonic acid on the basis of all units of uronic acid oligosaccharide uronic acid. The uronic acid oligosaccharides used in the invention is preferably derived from pectin, restate, alginate, chondroitin, hyaluronic acid, heparin, heparan, bacterial hydrocarbons, sialogogues, fucoidan, focalisation and/or carrageenan, preferably, from pectin and/or alginate, more preferably, from pectin, most preferably, polygalacturonic acid. The present uronic acid oligosaccharide is preferably a product of the degradation of pectin and/or product degradation of alginate. Preferably, the product of degradation of pectin is a hydrolyzed pectin (obtained by hydrolysis) and/or the lysate of pectin (derived beta-elimination). The product of the degradation of pectin preferably derived from fruit and/or vegetable pectin, preferably, Apple pectin, C is trudovogo pectin and/or sugar beet pectin. The product of the degradation of pectin preferably obtained by lathami and/or changes of temperature and pressure, preferably, beta-elimination. The product of the degradation of pectin preferably represents a lysate of pectin.

Preferably, the present composition contains uronic acid oligosaccharide with a DP of 2 to 250, preferably a DP of 2 to 100, more preferably a DP of 2 to 50, most preferably a DP of 2 to 20. Preferably, the present composition contains from 25 to 100 wt. -%, preferably, from 50 to 100% of the mass. the uronic acid oligosaccharide with a DP of 2 to 250 based on total weight of uronic acid in the composition, preferably a DP of 2 to 100, more preferably a DP of 2 to 50, most preferably a DP of 2 to 20.

The present uronic acid oligosaccharide can be preferably obtained by enzyme digestion of pectin by lathami pectin, liati, andprecautions and/or pectinate pectate.

In a preferred embodiment, at least one of the end units hexuronic acid uronic acid oligosaccharide has a double bond, which is preferably located between the position C4and C5end unit hexuronic acid. The double bond effectively protects against the attachment of pathogenic bacteria to intestinal epithelial cells. Preferably,one of the end units hexuronic acid may for example, be obtained by enzyme hydrolysis of pectin by liati.

The present composition preferably contains from 0.01 to 10 g of the uronic acid oligosaccharide with a DP of 2 to 250, preferably a DP of 2 to 100, per 100 g dry weight of the present composition, preferably, from 0.05 to 6 g, more preferably from 0.2 to 2 g per 100 g dry weight. The present composition preferably contains from 0.01 to 10 g of the oligosaccharide galacturonic acid with a DP of 2 to 250, preferably a DP of 2 to 100, per 100 g dry weight of the present composition, preferably, from 0.05 to 6 g, more preferably from 0.2 to 2 g

Thus, the present composition preferably contains various nevereverever oligosaccharides with different degrees of polymerization (DP). From the point of view of the fractions of oligosaccharides with different ranges of values of DP, the composition preferably has the following ratios:

a. (nevereverever oligosaccharides with a DP of 2 to 5):(nevereverever oligosaccharides with DP 6, 7, 8 and/or 9)>1; and/or

b. (nevereverever oligosaccharides with DP 10 to 60):(nevereverever oligosaccharides with DP 6, 7, 8 and/or 9)>1

Preferably, both the mass ratio of amount to more than 2, more preferably more than 5.

The present composition preferably contains from 0.5 to 75 g not digested oligosaccharides per 100 g dry mass, preferably from 0.5 to 50, the Crust is Asa composition preferably contains from 0.1 to 75 g of galactooligosaccharides per 100 g dry mass, preferably, from 0.1 to 50 g

The present method preferably includes assigning portions of food, containing from 0.05 to 25 g neperebrodivsego oligosaccharide, preferably, from 0.1 to 5 g

The present method preferably includes assigning portions of food, containing from 0.05 to 25 g galactooligosaccharides, preferably, from 0.1 to 5 g galactooligosaccharides.

Corticosteroid and inhibitor calcineurin

The present invention relates to the prevention of local application of corticosteroids and/or prevent the introduction of inhibitor calcineurin.

Preferably, to prevent the introduction of one or more of the following corticosteroids: alclometasone dipropionate, amcinonide, beclomethasone dipropionate, betamethasone benzoate, betamethasone dipropionate, betamethasone valerate, budesonide, clobetasol propionate, clobetasone butyrate, desonide, desoximetasone, diflorasone diacetate, valerate, flumetazon pivalate, fluchloralin acetonide, fluotsinolon acetonide, fluocinonide, fluocortin, drugs of fluocortolone, fluprednidene acetate, flurandrenolide, fluticasone propionate, halcinonide, halobetasol propionate, hydrocortisone, hydrocortisone acetate, hydrocortisone butyrate, hydrocortisone valerate, methylprednisolone acetate, mometazon furoate and triamcinolone acetonide and mixtures thereof.

Inhibitors kaltsin Irina are immunosupressant means, originally developed for systemic injections to prevent rejection of the allograft. These drugs inhibit calcineurin in the skin, which blocks the early activation of T-cells and cytokine release. Preparative forms for local use have been developed as alternatives to corticosteroids for topical use. Preferably, prevented the application of one or more of the following inhibitors calcineurin: pimecrolimus, tacrolimus, and mixtures thereof.

Infants

Infants suffer from skin diseases. The introduction of inhibitors of calcineurin infants is not recommended. Local corticosteroids in infants also have unwanted side effects. Therefore, especially desirable to reduce the use of these drugs in infants.

The authors found that the ingestion of the composition of the present invention prevents local application of corticosteroids and other dermatological preparations in infants aged up to one year. Therefore, the present invention is particularly preferable for infants and young children aged 0 to 24 months, preferably, ranging in age from 0 to 12 months, or in one embodiment, aged 0 to 6 months.

Composition

This compo is ice preferably introduced enterline, preferred oral.

The composition of the present invention is preferably a nutrient mixture, preferably a mixture for feeding infants. The composition according to the present invention can preferably be used as a complete substitute for breast-feeding for babies. The composition according to the present invention preferably contains a lipid, protein and carbohydrate, and preferably is introduced in liquid form. The present invention includes a dry composition, for example, powders, together with instructions on how to mix these dry compositions, in particular, nutrient mixture with a suitable liquid, such as water.

The present invention mainly relates to compositions, in which the lipid provides 5 to 50% of total calories, protein provides 5 to 50% of total calories, and the carbohydrate provides 15 to 90% of total energy. Preferably, the present composition of the lipid provides 35 to 50% of total calories, protein provides from 7.5 to 12.5% of total calories, and the carbohydrate provides from 40 to 55% of total calories. To calculate the % of total calories for the protein component, it is necessary to take into account the total energy provided by protein, peptides and amino acids.

The composition according to the present invention preferably contains the at least one lipid, selected from the group consisting of animal fat (excluding human lipids) and plant lipids. Preferably, the composition according to the present invention contains a combination of plant lipids and at least one oil selected from the group consisting of fish oil, animal oil, algae oil, oil of fungi and bacterial oil. The composition of the present invention, containing nevereverever oligosaccharides, eliminates human milk. Protein ingredients used in feed preparation, preferably selected from the group consisting of the non-human animal proteins (preferably, milk proteins, preferably proteins from cow's milk), vegetable proteins (preferably soy protein and/or rice protein), free amino acids and mixtures thereof. The composition according to the present invention preferably contains casein, whey, hydrolyzed casein and/or hydrolyzed whey protein, preferably the protein contains intact proteins, preferably, intact bovine whey proteins and/or intact cow's casein proteins. Because the composition of the present invention is particularly suitable for use in infants and young children with allergies, protein is preferably selected from the group consisting of hydrolyzed milk be the ka.

Liquid nutritional composition preferably has a caloric density of from 0.1 to 2.5 kcal/ml, more preferably, the caloric density of from 0.5 to 1.5 kcal/ml, most preferably from 0.6 to 0.8 kcal/ml

In particular, the present invention provides a composition as described above, followed by evidence (for example, printed material)indicating that the introduction of the composition (for example, a baby or a young child) prevents the need to use corticosteroids; reduces the duration of use of corticosteroids and/or reduces the likelihood that the individual will require local application of corticosteroids to prevent skin diseases.

EXAMPLES

EXAMPLE 1: a Clinical study

In a randomized, controlled, double-blind European multicenter study (7 centers in 5 countries) were included 1187 healthy term infants and small children without family history of atopy, or receiving infant formula with added prebiotic mixture of the present invention (galactooligosaccharide, fructo-oligosaccharides and oligosaccharides derived from protein, 8 g/l mixture), or a standard nutrient mixture (control)or breast milk (the latter were not randomized). The number of children in the amount of 186 (15,7%) dropped out from the study (without group is Alicia). 835 children completed the study in accordance with the Protocol, i.e. that completed the study and correctly kept feeding scheme: 292 child in the group a new prebiotic, 300 children in the control group and 243 of the child in the comparison group. Corticosteroids and dermatological preparations was observed in the analysis of FAS in 16 children from the group of prebiotics, while it was observed in 40 children in the control group (Fisher's test p=0,0018) (PPS 10 vs. 29, p=0,0025).

EXAMPLE 2: Track

The composition of the nutrient mixture for infants and young children, containing 100 ml ready for feeding the mixture: 1.6 g protein, 3.6 g fat, 6.4g of digestible carbohydrates (mainly lactose), 0.8 g not digested oligosaccharides, of which the composition contains 0,54 g transplantationfollow, 0.06 g of inulin and 0.2 g of hydrolyzed pectin (obtained by treating citrus pectin by liati).

1. The use of a composition containing galactooligosaccharide, fructo-oligosaccharide and uronic acid oligosaccharide, upon receipt of a composition for oral administration for a baby to prevent local application of corticosteroids and/or prevent the introduction of inhibitor calcineurin the child, where the uronic acid oligosaccharide is a product of the degradation of pectin and/or product degradation of alginate and where CA is out of corticosteroids and/or the introduction of inhibitor calcineurin is intended for treatment of eczema, childhood eczema, atopic dermatitis, dermatitis herpetiformis, contact dermatitis, sebrango dermatitis, neurodermatitis, psoriasis and intertrigo.

2. The use according to claim 1, where the uronic acid oligosaccharide is a product of the degradation of pectin.

3. The use according to claim 1, where the infant is aged 0 to 12 months.

4. The use according to any one of claims 1 to 3, where the composition comprises lipid, protein and carbohydrate, where the lipid provides 5 to 50% of the total calories of the composition, protein provides 5 to 50% of the total calories of the composition and carbohydrate from 15 to 90% of the total calories of the composition.

5. The use according to any one of claims 1 to 3 to prevent drug selected from the group consisting of alklometazon dipropionate, amcinonide, beclomethasone dipropionate, betamethasone benzoate, betamethasone dipropionate, betamethasone valerate, budezonida, clobetasol propionate, clobetasone of butyrate, desonide, desoximetasone, diflorasone diacetate, diflucortolone valerate, flumetazon pivalate, fluchloralin acetonide, fluoqinolona acetonide, fluocinonide, fluocortolone, drugs of fluocortolone, fluprednidene acetate, flurandrenolide, fluticasone propionate, halcinonide, halobetasol propionate, hydrocortisone, hydrocortisone acetate, hydrocortisone butyrate, hydrocortisoneidocaine, methylprednisolone acetate, mometasone furoate, triamcinolone acetonide, pimecrolimus, tacrolimus, and mixtures thereof.



 

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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.

27 cl

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: biotechnology.

SUBSTANCE: monocytes are isolated from venous blood MNCs using the Percoll cushion bi-gradient of density: 47.5% SIP and 15% SIP, respectively, at cooling to +4°C. The monocytes are placed in a completely nutritional culture medium with adding 20 ng/ml IL-4 and 20 ng/ml GM-CSF. The completely nutritional culture medium is replaced on the day 3 of cultivation. On the day 4 of cultivation the antigen of infectious origin Opisthorchis felineus is added at a dose of 40 mcg/ml and maturation of dendritic cells is simultaneously induced with lipopolysaccharide E.coli of serotype 055: B5 in a dose of 1 mcg/ml. On the day 6 of cultivation the dendritic cells are washed and analysed.

EFFECT: use of the method provides obtaining the mature, antigen-loaded dendritic cells.

2 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to organic chemistry, namely to new 1,2-dihydroquinoline derivatives of general formula , or to a pharmaceutically acceptable salt thereof, wherein R1 represents a lower alkyl group; R2 represents a hydrogen atom; each of R3 and R4 represents a lower alkyl group; R5 represents a lower alkyl group; R6 represents a halogen atom, a lower alkyl group, a lower alkoxy group, a nitro group; X represents -CO-, -C(O)NR8 - or -S(O)2-; each of R7 and/or R8 may be identical or different, and represents a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower cycloalkyl group, a phenyl or naphthyl group, a saturated or unsaturated monocyclic 5- or 6-member heterocyclyl with one or two heteroatoms specified in nitrogen, oxygen and sulphur atoms, and 3-5 carbon atoms in a cycle, a lower alkoxy group, a phenoxy group; provided R7 and/or R8 represent a lower alkyl group, a lower alkoxy group, the mentioned lower alkyl group and lower alkoxy group may contain one or three groups specified in a halogen atom, a phenyl group, an unsubstituted monocyclic 6-member heterocyclyl with one heteroatom specified in a nitrogen atom, and 5 carbon atoms in a cycle, a lower alkoxy group, and -NRaRb as a substitute (substitutes); provided R7 and/or R8 represent a phenyl group, a saturated or unsaturated monocyclic 5- or 6-member heterocyclyl with one or two heteroatoms specified in nitrogen, oxygen and sulphur atoms, and 3-5 carbon atoms in a cycle, a phenoxy group, the mentioned phenyl group, saturated or unsaturated monocyclic 5- or 6-member heterocyclyl with one or two heteroatoms specified in nitrogen, oxygen and sulphur atoms, and 3-5 carbon atoms in a cycle, phenoxy group may contain one or two groups specified in a halogen atom, a lower alkyl group, a halogen-substituted lower alkyl group, a phenyl group, a hydroxyl group, a lower alkoxy group, a halogen-substituted lower alkoxy group, a lower alkylthio group, a lower alkylcarbonyl group, a lower alkoxycarbonyl group, a lower alkylcarbonyloxy group, -NRaRb, a nitro group and a cyano group as a substitute (substitutes); Ra and Rb may be identical or different, and each of them represents a hydrogen atom, a lower alkyl group, a lower alkoxycarbonyl group; Y represents a lower alkylene group; Z represents an oxygen atom; p is equal to 2, provided p is equal to 2, R6 may be identical or different. The invention also relates to a pharmaceutical composition and a glucocorticoid receptor modulator of the compound of formula (1).

EFFECT: there are produced new 1,2-dihydroquinoline derivatives possessing glucocorticoid receptor binding activity.

7 cl, 1 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to an aminopropylidene derivative presented by formula wherein R1 and R2, which may be identical or different, represent hydrogen or a substitute specified in the following (a)-(c), provided the case of both representing hydrogen is excluded: (a) carbonyl substituted with hydroxy, alkoxy or hydroxy alkylamino, (b) carbonylalkyl substituted by hydroxy or alkoxy, and (c) acrylic acid including its alkyl ester, R3 and R4, which may be identical or different, represent hydrogen, alkyl which may be substituted by phenyl or cycloalkyl, or R3 and R4, which together form a heterocyclic ring with a nitrogen atom bound thereto, represent pyrrolidino, piperidino, which may be substituted by oxo or piperidino, piperazinyl substituted by alkyl or penyl, morpholino or thiomorpholino; A means oxo or is absento, B represents canbon or oxygen; one of X and Y represents carbon, while the other one represents sulphur, a part represented by a dash line represents a single bond or a double bond, and a wavy line represents a cys-form and/or a transform. Also, the invention refers to a pharmaceutical composition exhibiting histamine receptor antagonist activity on the basis of said compounds.

EFFECT: there are produced new compounds and pharmaceutical compositions thereof, which can be used in medicine for treating asthma, allergic rhinitis, pollen allergy, hives and atopic dermatitis.

10 cl, 12 tbl, 58 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a new method for the chemical synthesis of asymmetrically or symmetrically substituted β-(1→6)-bound glucosamine disaccharide of formula (1), as well as to a method for purifying it. The invention declared the intermediate compounds referred to the given method.

EFFECT: invention refers to a pharmaceutical composition comprising the mentioned compounds, and to the use of the compounds in treating the disorders affected by immune system activity modulation, including the inhibition or activation of the immune system, such as a disorder selected from immune disorders and/or cancer.

26 cl, 8 ex, 26 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, and represents a local skin composition which is an oil-in-water-in-oil emulsion containing a water phase with a dispersed lipophilic phase containing calcipotriol or monohydrate in the dissolved form; a non-ionic surfactant specified in a group consisting of polyethylene glycol glycerides and C6-20 fatty acids, polyoxyethylene C8-20 alkyl ethers or polysorbates and a lower alkanol as a co-solvent; the above water phase is dispersed in a pharmaceutically acceptable anhydrous lipophilic carrier or base.

EFFECT: invention provides the effective dissolution of calcipotriol with the lower content of a lower alcohol, as well as the good penetration of calcipotriol into the viable skin layers, higher biological activity and less skin irritation.

26 cl, 5 ex, 7 tbl, 6 dwg

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