Inhalation preparation for treating bronchail asthma and chronic obstructive pulmonary disease and method for preparing it

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to medicine and pharmaceutical industry and describes an inhalation preparation for treating bronchial asthma and chronic obstructive pulmonary disease, containing micronized budesonide and micronised formoterol fumarate dehydrate as active ingredients, wherein the preparation contains a carrier presented by lactose of average particle diameter 1 to 10 mcm and sodium benzoate of bulk density 0.30-0.50 g/cm3, in the following proportions of the ingredients per a dose of the preparation: budesonide 50 mcg - 800 mcg, formoterol fumarate dehydrate 4.5 mcg - 18 mcg, lactose 5 mg - 50 mg, sodium benzoate 0.01 mg - 5 mg. What is also described is a method for producing the given preparation.

EFFECT: invention provides a higher percentage of a fraction of the active substances and respectively higher effectiveness.

4 cl, 8 ex

 

The invention relates to medicine and the pharmaceutical industry and relates to a dry powdered preparation containing two highly effective pharmaceutical substances in mikronizirovannuu form, allowing to penetrate into the bronchi and alveoli of the lungs and prepared in a special way auxiliary substance allows to dose, and to disaggregate the active substance.

Bronchial asthma (BA) is one of the most common diseases of the respiratory system among people of all ages. In Russia BA suffers from 5 to 7% of the adult population. Severity of disease: 30% of patients - mild course of the disease, a 50% moderate and 20% severe. BA is the cause of 0.4% of all cases of population for medical care, 1.4 percent of hospitalizations. Chronic obstructive pulmonary disease (COPD) is another common chronic disease of the respiratory system, which is accompanied by chronic relapsing inflammation of the bronchial wall. COPD is characterized by a steady progression, even when outside of an exacerbation occurs increase of bronchial obstruction, the accession of complications, and patients gradually lose their ability to work. According to some reports in Russia more than 11 million people suffer from COPD. Thus, there is significant is th the demand for drugs, effective against respiratory diseases, especially asthma and chronic obstructive pulmonary disease.

The level of technology.

The main place in modern therapy of these diseases is inhalation therapy. When using inhalation methods offer the possibility of creating a high concentration of the drug directly into the bronchi and lungs, reduces the possibility of systemic effects. This is due to the lack of binding to blood proteins, modifications in the liver and other drug prior to its action. The use of inhalants considerably reduces the total dose of the drug required for therapeutic effect.

To achieve the effect of deep penetration into the lungs it is necessary that the diameter of the particles of biologically active substances does not exceed 5-10 μm. Fine (micronized) biologically active substances used for inhalation, are characterized by high specific surface of the particles, which leads to the resulting distribution of forces of interaction and in turn increase the adhesion and cohesion of the particles. Since biologically active substance or mixture of substances injected the patient with the help of special devices, the drug should not be late in the specified device and naturalise when spraying. That is the necessary selection of these media, which would ensure effective delivery of the drug when it is placed in inhaled dosing device.

Known inhalation composition for the treatment of bronchial asthma, containing lekarstvennye tools used in bronchial asthma, and as a diluent is sodium benzoate. Sodium benzoate is in the composition is from 20 to 99.8%. The proposed composition does not cause side effects (e.g., fungal diseases of the mouth), you might encounter when using as a diluent Sugars (EN 2054932 C1).

Also in Russia the patented composition containing as the sole excipients sodium benzoate. The authors explain his use of antifungal action of sodium benzoate (a fungal infection of the oral cavity during inhalation therapy, especially in the application of glucocorticosteroids, are quite common (RF patent 2242972).

However, these compositions because of the properties of sodium benzoate easily aggregated, do not provide a respirable fraction much more than 15-17%. Introduction the preparation benzoic acid or succinic acid slightly increases the antifungal effect but does not increase the respirable fraction.

Lactose as a carrier is used in almost all powder inhalation drug is H. Its use is indicated in many Russian and foreign patents, such as patents of the Russian Federation 2140260 and 2194497. However, as a rule, this media does not provide a satisfactory value of the yield of fine particles, and thus the ease of penetration into the lungs.

As the closest analogue may be specified drug Symbicort company AstraZeneca in mnogomodovoi the inhaler dry powder "Turbuhaler" (http://www.risnet.m/tn_index_id_l 7658.htm).

Composition active substances: Budesonide+Formoterol fumarate dehydrate.

Dosage:

I. 80+4.5 µg/dose;

II. 160+4.5 µg/dose;

III. 320+9 µg dose.

Excipient: lactose monohydrate - 491 mg/dose.

Known composition does not provide a significant amount of respirable fraction that determines the effectiveness of inhalation.

The present invention is to develop effective inhalation composition for the treatment of asthma and COPD.

This task is solved by a new drug for inhalation containing as active substances micronized Budesonide and micronized Formoterol fumarate dehydrate, and as a carrier lactose with average particle sizes from 1 to 10 μm and sodium benzoate with a bulk density in the range of 0.30-0.50 g/cm3preferably of 0.38 to 0.44 g/cm3when the following component to the dose of p is eparate:

Budesonide 50 mcg to 800 mcg

Formoterol fumarate dehydrate to 4.5 ug-18 ug

Lactose 5 mg to 50 mg

Sodium benzoate 0.01 mg to 5 mg

Technical result: a higher percentage of respirable fraction of the active substances and therefore higher efficiency.

The drug is intended for treatment of respiratory diseases such as bronchial asthma and chronic obstructive pulmonary disease.

Patented composition is a powder containing as active substance budesonide and formoterol fumarate, which have different mechanisms of action and showing an additive effect, and as excipients lactose and sodium benzoate.

Glucocorticosteroid local action budesonide - inhalation procedure has potent anti-inflammatory action in the bronchial tubes, reducing the severity of symptoms and the frequency of exacerbations of asthma.

Selective agonist β2-adrenoreceptor formoterol has a bronchodilator effect in patients with obstruction of the respiratory tract. The effect of the drug occurs within 3 minutes and lasts up to 12 hours after inhalation.

The drug can be placed in gelatin capsules and applied using a special device - dose inhaler dry powder, for example Inhaler CDM, firm Qualitec Industria or container mnogonatsionaljnoy, for example Ziklohaler, firm "Pulimood".

For inhalation purposes in diseases of the lungs using micronized substance (see the above prior art) with an average particle size of from 0.1 μm to 10 μm. Preferably the proportion of the particles of the active component with dimensions of 0.5-5 μm is not less than 95%, even more preferably 99% by mass.

Another object of the invention is a method of obtaining the drug.

The method of producing drug for inhalation is characterized by the fact that micronizer substances active substances in the planetary mill, sieved lactose with an average particle size of 100 to 120 μm, followed by micronization to medium particle sizes from 1 to 10 μm, sift sodium benzoate to obtain a bulk density in the range of 0.30-0.50 g/cm3preferably of 0.38 to 0.44 g/cm3mixed pre formoterol fumarate with micronized lactose in a ratio of 1:16,6-35,6 add to the mixture of micronized budesonide and mix thoroughly, then injected into the mixture of sodium benzoate and the remaining amount of lactose is stirred at a speed of 40-45 rpm for 12-15 minutes

If necessary, make the packaging of the drug. Depending on the type of inhaler packing are either in hard gelatin capsule or container or road is s-parenteral multi-dose inhalers, or other devices for inhalation.

Tests.

The preparation obtained by the above technologies, and control the drug was tested in accordance with requirements established for powders for inhalation of the European Pharmacopoeia. Of particular importance for inhalation drugs represents the fraction of fine particles of active substances, measured in μg/dose or percent and determined in the course of aerodynamic testing. The magnitude of this fraction, known as respirable, determines the effectiveness of the preparations for inhalation for the treatment of respiratory organs. Determination of the respirable fraction is carried out with the use of devices described in the European and American pharmacopoeias. The most often used vosmiseriyny the Andersen impactor (device D of the European Pharmacopoeia), as it gives the opportunity to explore in more detail the particle size distribution in the range from 0.5 μm to 10 μm and more. The European Pharmacopoeia defines terms analysis - volume pumped air 4 l, the flow rate of 28.3 l/min, although it allows the use of other speed. However, each specific model of Andersen impactor designed for a certain flow rate of air and cannot be used on another. According to the results of testing various preparaton respirable fraction and the results of the effectiveness of these drugs in medical practice, we can assess the magnitude of respirable fraction: ^Poor, 25% good, 35% and above - excellent (however, it is necessary to take into account the pharmacological properties of the active substances). This estimate is conditional; it depends on the machine on which the study was conducted, the methods of sampling and analysis methods of calculation.

In the study of mixtures acceptable carriers, it was discovered that a mixture of lactose and sodium benzoate, prepared by the above method, when tested on the Andersen impactor using the inhaler Inhaler CDM (the volume of air pumped through 4 l, the flow rate of 28.3 l/min), has a higher percentage of the respirable fraction of the active substances, than a similar product that contains as a carrier only lactose. Specific values for respirable fractions (measured by budesonide, steps 2-7 and filter) are shown in the examples. The preparation containing a mixture of lactose and sodium benzoate was easily dotirovala in capsules and containers, so you can expect that the sodium benzoate will show their antifungal properties.

The homogeneity of the emitted dose was within the requirements of the European Pharmacopoeia.

Example 1

Budesonide 50 mg;

Formoterol fumarate 4.5 µg;

Lactose 10 mg;

Sodium benzoate 0.01 mg

Respirable fraction 30,1%

Technology of production of drugs:

ICRI is the shadowing of the active substances is carried out in a planetary mill, for example, the company Retsch PM 400. Ensure that the proportion of particles with sizes of 0.5-5 μm was not less than 99% by weight. Preparation of auxiliary substances produced as follows.

Lactose with an average particle size of 100-120 microns (e.g Inhalac® 100, the company Meggle, Lactohale®, the firm Domo or any other relevant requirements of the European or us Pharmacopoeia), sieved through a sieve with 200 μm. Lactose micronizer to particle sizes from 1 to 10 μm in the mill or purchase from the manufacturers with the required particle size. Sodium benzoate is sifted through a sieve of 400 μm, the loaded balls of stainless steel screening machine with intense vertical oscillations, for example Model AS 200 basic company Retsch, Germany). For each analytical sieve with mesh size 400 µm put on 2 kg of balls, stainless steel with a diameter of 9 mm and load of sodium benzoate. Set the process mode of operation of the sieve analyzer: time sifting 10 min, the amplitude of 2.5 - 3 mm bulk density sifted sodium benzoate obtained in the range of 0.30-0.50 g/see

Pre-mix formoterol fumarate with micronized lactose in a ratio of 1:17,8 To this mixture of micronized budesonide and mix thoroughly. This procedure preserves the ratios of active substances in Lek is rstendamm the drug. Then upload sodium benzoate, following this, the remaining amount of lactose. Include mixing at a speed of 42 rpm and maintain it within 14 minutes

Depending on the type of inhaler packing are either in hard gelatin capsules or containers of parenteral multi-dose inhalers, or other devices for inhalation.

Example 2

Budesonide 80 mcg;

Formoterol fumarate 4.5 µg;

Lactose 10 mg;

Sodium benzoate 5 mg

Respirable fraction 33,1%

Example 3

Budesonide 160 mcg;

Formoterol fumarate 9 mcg;

Lactose 50 mg;

Sodium benzoate 2 mg

Respirable fraction 42,5%

The drug is produced as in example 1. Premixing of formoterol fumarata with micronized lactose in a ratio of 1:35,6. Stirring at a speed of 40 rpm and maintain it within 15 minutes

Example 4

Budesonide 200 mcg;

Formoterol fumarate 18 mcg;

Lactose 10 mg;

Sodium benzoate 2 mg

Respirable fraction of 37.5%

Example 5

Budesonide 400 mcg;

Formoterol fumarate 9 mcg;

Lactose 25 mg;

Sodium benzoate 5 mg

Respirable fraction 39,9%

The drug is produced as in example 1. Premixing of formoterol fumarata with micronized lactose in a ratio of 1:16,6. Bulk density sifted sodium benzoate obtained in the range of 0.38 to 0.44 g/see

Example 6

B is desonide 800 mcg;

Formoterol fumarate 9 mcg;

Lactose 10 mg;

Sodium benzoate 1 mg

Respirable fraction 38,1%

Example 7

Budesonide 800 mcg;

Formoterol fumarate 4.5 µg;

Lactose 12.5 mg;

Sodium benzoate 2.5 mg

Respirable fraction of 38.7%

Example 8

Budesonide 80 mcg;

Formoterol fumarate 4.5 µg;

Lactose 10 mg;

Respirable fraction of 12.3%.

1. Inhalation drug for the treatment of bronchial asthma and chronic obstructive pulmonary disease, comprising as active substances micronized Budesonide and micronized Formoterol fumarate dehydrate, characterized in that it contains as a carrier lactose with average particle sizes from 1 to 10 μm and sodium benzoate with a bulk density in the range of 0.30-0.50 g/cm3if the following content of components per dose:

Budesonide 50 mg800 mcg
Formoterol the fumarate dihydrate 4.5 µg18 mcg
Lactose 5 mg50 mg
Sodium benzoate 0.01 mg5 mg

2. The preparation according to claim 1, characterized in that the proportion of micronized particles of the active component with dimensions of 0.5-5 m is m is not less than 95 mass%.

3. The preparation according to claim 1, characterized in that the bulk density of the sodium benzoate is in the range of 0.38 to 0.44 g/cm3.

4. The method of obtaining the inhalation of the drug according to any one of claims 1 to 3, characterized in that micronizer substances active substances in the planetary mill, sieved lactose with an average particle size of 100-120 microns with them, followed by micronization to medium particle sizes from 1 to 10 μm, sift sodium benzoate to obtain a bulk density in the range of 0.30-0.50 g/cm3mixed pre formoterol fumarate with micronized lactose in a ratio of 1:16,6-35,6 add to the mixture of micronized budesonide and mix thoroughly, then injected into the mixture of sodium benzoate and the remaining amount of lactose is stirred at a speed of 40-45 rpm for 12-15 minutes



 

Same patents:

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to emergency medicine, and may be used for reducing and managing the bronchial asthma status. That is ensured by introducing human urotensin 2 (hU) antiserum that is a hormone of the caudal neurosecretory system (CNSS) one a day intracutaneously into a palmar surface of the arm in 2-3 points in a dose of 0.1- 0.2 ml and 25% magnesium sulphate intravenously in a dose of 5-10 ml twice a day in a combination with intravenous glucocorticosteroids and bronchial spasmolytic inhalations.

EFFECT: method enables relieving the patients from the bronchial asthma status fast and effective due to its simplicity with the lower drug consumption and reduced length of treatment.

1 tbl, 2 ex

FIELD: chemistry.

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FIELD: medicine, pharmaceutics.

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11 cl, 19 ex, 4 tbl

FIELD: chemistry.

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19 cl, 6 tbl.

FIELD: medicine, pharmaceutics.

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27 cl

FIELD: biotechnologies.

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EFFECT: improved properties of compounds.

FIELD: medicine, pharmaceutics.

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18 cl, 393 ex

FIELD: medicine, pharmaceutics.

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7 cl, 1 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula

,

where: A is CA1; E is CE1; W is (CH2)n; Y is (CH2)P; n and p are independently equal to 0 or 1; R1 is a phenyl which is substituted with a phenyl {which is optionally substituted with a halogen, hydroxy, CH(O), CO2H, C1-4alkyl, C1-4alkyl-(N(C1-4alkyl)2), C1-4alkyl(NH2), C1-4alkyl(NH(C1-4alkyl)), C1-4hydroxyalkyl, CF3, C1-4alkylthio, C1-4alkyl(heterocyclyl) or C1-4alkylNHC(O)O(C1-4alkyl)} or a heterocyclyl; and the heterocyclyl is optionally substituted with C1-6alkyl; R2 is NHC(O)R3; and R3 is C1-4alkyl {substituted with NR7R8 or a heterocyclyl}, C3-7cycloalkyl (optionally substituted with a NR43R44 group) or a heteroaryl; where R7, R8, R43 and R44 are as defined in claim 1; wherein the heteroaryl is optionally substituted with a halogen, C1-4alkyl, CF3, C1-4alkoxy, OCF3, heterocyclyl or an amino(C1-4alkyl) group; R7 and R8 are independently C1-6alkyl; A1, E1 and G1 are independently hydrogen or halogen; unless otherwise stated, the heterocyclyl is optionally substituted with C1-6alkyl; R25 is C1-6alkyl; R50 is hydrogen or C1-6alkyl (optionally substituted with a NR51R52 group); R30, R36, R40, R42 or R44 is independently hydrogen, C1-6alkyl(optionally substituted with hydroxy, C1-6alkoxy, C1-6alkylthio, C3-7cycloalkyl (which is optionally substituted with hydroxy) or NR45R46), C3-7cycloalkyl (optionally substituted with a hydroxy(C1-6alkyl) group) or a heterocyclyl (optionally substituted with C1-6alkyl); R29, R35, R39, R41, R43, R45, R46 and R51 are independently hydrogen or C1-6alkyl; where the heterocyclyl is a non-aromatic 5- or 6-member ring containing one or two heteroatoms selected from a group comprising nitrogen and oxygen; and where the aryl is phenyl or naphthyl; and where the heteroaryl is an aromatic 5- or 6-member ring, optionally condensed with another ring (which can be carbocyclic and aromatic or non-aromatic), having one or two heteroatoms selected from a group comprising nitrogen, or a pharmaceutically acceptable salt thereof. The invention also relates to a pharmaceutical composition based on said compounds.

EFFECT: obtaining novel compounds and a pharmaceutical composition based on said compounds, which can be used in medicine to treat a PDE4-mediated disease state.

10 cl, 81 dwg, 15 tbl, 375 ex

FIELD: chemistry.

SUBSTANCE: invention relates to pyrazinone derivatives of formula (I):

, where R1, R2, R3, R4, R5, R and R7 are as defined in claim 1 of the invention. The invention also describes a crystalline form, compounds of formula I, use of the compound of formula I in producing a medicinal agent for treating chronic obstructive pulmonary disease. A pharmaceutical composition and a pharmaceutical product are also described. Methods of obtaining compounds of formula I are also described.

EFFECT: novel compounds which can be used in therapy are obtained and described.

20 cl, 334 ex, 15 tbl, 12 dwg

Iimmunomodulator // 2504371

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, namely to an immunomodulator. An immunomodulator for the immunocorrection accompanying the integrated treatment of chronic non-specific pulmonary diseases, chronic obstructive pulmonary disease, bronchial obstruction syndrome, chronic bronchial pneumonia, pulmonary fibrosis, tracheobronchitis, chronic laryngitis, pulmonary, tracheal and pharyngeal cancer; the immunomodulator is prepared by mixing a water infusion of rose bay leaves and a water infusion of yellow melilot taken in equal proportions, with a cattle lung and larynx powder, settling the prepared mixture, keeping on a boiling water bath, cooling; further, the mixture is filtered; the prepared solution is added with cattle blood serum containing leukaemia oncovirus antibodies, hemlock infusion, ascorbic and sorbic acids until all the ingredients fully dissolved; the prepared solution is placed in the water bath, cooled, filtered, sterilised under certain conditions.

EFFECT: above preparation provides higher effectiveness and reduces the length of treating the above diseases, and ensures the higher immunobiological properties of the human body.

3 ex

FIELD: biotechnologies.

SUBSTANCE: invention refers to derivatives of oxazolopyrimidine in any of their stereoisomeric forms, or in the form of a mixture of stereoisomeric forms specified in Claim 1.

EFFECT: oxazolopyrimidine derivatives having agonistic activity in relation to Edg-1 receptor.

5 tbl, 319 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.

SUBSTANCE: invention refers to medicine, namely to pulmonology and physiotherapy, and may be used for treating acute pneumonias in debilitated patients living in industrial cities. That is ensured by 10 daily ultrasonic inhalations of 1% placenta hydrolysate at temperature 35°C for 10 minutes on an empty stomach or 40-60 minutes after meals. The inhalations are followed by the exposure to an ultra-high frequency electric field generated by automatically resonating UHF-80-3 Undaterm apparatus of output power up to 80 Wt, high-frequency oscillation frequency 27.12±0.6 MHz. The UHF exposure covers a patient sitting of a wooden chair. Condenser plates, each of the diameter 180 mm spaced 3 cm are placed on front and back surfaces of a chest above the inflammation centre from each side. An UHF dose is low-heat, has a power of 40-60 Wt; the procedure length is 10 minute; the therapeutic course makes 10 daily procedures. After 30 minutes, the UHF exposure is followed by medicine electrophoresis through 5% placenta hydrolysate applied on one of the temporary spacers. The exposure is generated by Potok-1 apparatus having current intensity 15-20 mA; the procedure length makes 20 minutes; the therapeutic course is 10 daily procedures with the patient lying on back on a bed. Two electrodes of the same size 10x15 cm are placed in a projection of the pathological centre, i.e. the first electrode is placed on the right or on the left on the back, and the second one - on the right or on the left at the front.

EFFECT: providing faster relief of the pathological process in the pulmonary tissue, prevented development of any complication and formation of the pulmonary chronic process, including due to the manifested secretolytic effect, the high effect of bronchial apparatus drainage, normalised immune status of the respiratory mucosa.

3 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to dihydrothienopyrimidinesulphoxides of formula 1, and pharmaceutically acceptable salts thereof , where X denotes SO, R1 denotes H, R2 denotes H or a residue selected from C1-C10alkyl, which is optionally substituted with one or more residues selected from OR2.1, where R2.1 denotes H or C1-C6alkyl, R2.2 and R2.3 independently denote H or C1-C6alkyl, where Het is a 6-member monocyclic, saturated heterocycle containing 1 heteroatom selected from N or O, and where the hetaryl is a 5-11-member mono- or bicyclic, optionally anellated heteroaryl containing 1, 2 or 3 heteroatoms independently selected from N, S or O, and where the cycloalkyl can be saturated, or R2 denotes a monocyclic C3-cycloalkyl, which is optionally substituted with a residue selected from a branched or linear C1-C6alkanol, C1-C3alkylene-OR2.1, or R2 denotes phenyl which is optionally substituted with a halogen, or R2 denotes a residue selected from Het and hetaryl, each optionally substituted with one or more residues selected from halogen, OH, oxo group and OR2.1, C1-C6alkyl, and where R3 denotes a bicyclic 9-11-member unsaturated or partially saturated heterocycle which is optionally substituted with one or more residues selected from a group comprising F, O, Br, CF3, CN, OH, methyl, ethyl, propyl, isopropyl, -O-methyl, -O-ethyl, phenyl, NR2.2R2.3, where the phenyl is optionally substituted with F, Cl or Br. The invention also relates to pharmaceutical compositions based on said compounds, having phosphodiesterase 4 (PDE4) inhibiting activity.

EFFECT: obtaining novel compounds and pharmaceutical compositions based thereon, which can be used in medicine to treat respiratory or gastrointestinal complaints or diseases, inflammatory diseases of joints, skin or eyes, diseases of the peripheral or central nervous system or cancers.

20 cl, 1 tbl, 156 ex

FIELD: chemistry.

SUBSTANCE: invention relates organic chemistry and specifically to novel pyridine amide derivatives of general formula I where n equals 1; R1 and R2 together denote a residue selected from a group consisting of -CH=N-NH- and -CH=CH-N=CH-, which is bonded in any desirable direction to the parent structure or R2 and R3 together denote a residue selected from a group consisting of -CH=N-NH-; -CR28=N-NH-; -S-C(=S)-NH-; -S-CR29=N-; -N=CR30-O-; -N=CH-NH-; -N=N-NH-; -O-CH2-O-; -CH2-CH2-CH2-NH, -O-CH2-CH2-O-; -N=CH-CH=N-; -CH=CH-CH=N-, which is bonded in any desirable direction to the parent structure, or R3 and R4 together denote a -CH=N-NH- residue, which is bonded in any desirable direction to the parent structure, or R4 and R5 together denote a -CH=N-NH- residue, which is bonded in any desirable direction to the parent structure, and the rest of the residues R1, R2, R3, R4 and R5, mutually independently, in each case denote H; where R28 denotes F; Cl; Br or I; R29 and R30, mutually independently, in each case denote -NH-C(=O)-R31; -NH2; -NH-S(=O)2-R32; -NH-C(=O)-O-R33; -S-R34; where R31, R32, R33 and R34, mutually independently, in each case denote a straight or branched, saturated, unsubstituted aliphatic C1-10 residue; R6 denotes H or denotes a straight or branched, saturated, unsubstituted aliphatic C1-10 residue; R7 denotes hydrogen or -OH; R denotes -CF3; or denotes an unsubstituted tert-butyl residue; T denotes C-R35 and U denotes C-R36, V denotes N and W denotes C-R38; where R35 and R36 denote H; where R38 denotes -NR40R41; -OR42 or -SR43; where R40, R41, R42 and R43, mutually independently, in each case denote a straight or branched, saturated, unsubstituted aliphatic C1-10 residue; or denote a saturated, unsubstituted 3-, 4-, 5-, 6-, 7-, 8- or 9-member cycloaliphatic residue, or where R40 and R41 in each case together with a nitrogen atom as a ring member which binds them together, form a saturated 6-member heterocycloaliphatic residue, optionally substituted with one R57 residue, where R57 denotes a straight or branched, saturated, unsubstituted aliphatic C1-10 residue; in each case in form of corresponding physiologically acceptable salts. The invention also relates to a method of producing a compound of formula I, a medicinal agent based on the compound of formula I and use of the compound of formula I.

EFFECT: obtaining novel amide derivatives of pyridine, useful in treating vanilloid receptor 1 mediated diseases.

25 cl, 1 tbl, 18 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (1) or salts thereof, where in formula (1) R1 is a lower C1-C6alkyl group, a lower C3-C6cycloalkyl group, a phenyl group, a heterocyclic group, which relates to a residue formed by removing a hydrogen atom from a saturated or unsaturated monocyclic heterocyclic ring containing one, two or three heteroatoms in the ring, selected from a nitrogen atom, an oxygen atom and a sulphur atom, or a phenyl(C1-C6alkyl) group; in cases when R1 is a lower C1-C6alkyl group, that lower C1-C6alkyl group can have, as substitute(s), one, two or three groups selected from a halogen atom, a heterocyclic group which relates to a residue formed by removing a hydrogen atom from a saturated monocyclic heterocyclic ring containing one or two heteroatoms in the ring, selected from a nitrogen atom and an oxygen atom, a carboxyl group, a lower C1-C6alkoxycarbonyl group, a lower C1-C6alkylamino group, a lower C1-C6alkylamino group, substituted with a lower C1-C6alkylamino group, a lower C1-C6alkylamino group, substituted with a phenyl group; in cases when R1 is a phenyl group, a heterocyclic group which relates to a residue formed by removing a hydrogen atom from a saturated or unsaturated monocyclic heterocyclic ring containing one, two or three heteroatoms in the ring, selected from a nitrogen atom, an oxygen atom or a sulphur atom, or a phenyl(C1-C6alkyl) group, that phenyl, heterocyclic or phenyl(C1-C6alkyl) group can contain, as substitute(s), one, two or three groups selected from a halogen atom, a lower C1-C6alkyl group, a hydroxyl group or a lower C1-C6alkoxy group; R2 is a hydrogen atom or a lower C1-C6alkyl group; R3 is a hydrogen atom or a lower C1-C6alkyl group; R4 and R5 can be identical or different and are a hydrogen atom or a lower C1-C6alkyl group; R6 is a hydrogen atom or a lower C1-C6alkyl group; R7 is a phenyl group or a heterocyclic group which relates to a residue formed by removing a hydrogen atom from a saturated monocyclic heterocyclic ring containing one heteroatom in the ring, selected from an oxygen atom and a sulphur atom; in cases where R7 is a phenyl group or a heterocyclic group which relates to a residue formed by removing a hydrogen atom from a saturated monocyclic heterocyclic ring containing one heteroatom in the ring, selected from an oxygen atom and a sulphur atom, that phenyl or heterocyclic group can contain, as substitute(s), one or two groups selected from a halogen atom, a lower C1-C6alkyl group, a hydroxyl group, a lower C1-C6alkoxy group and a nitro group; W is an oxygen atom or NR8; R8 is a hydrogen atom or a lower C1-C6alkyl group; X is an oxygen atom or a sulphur atom; Y is a lower C1-C6alkylene group; Z is an oxygen atom, a sulphur atom, NR9 or OCO; R9 is a hydrogen atom or a lower C1-C6alkyl group. The invention also relates to a pharmaceutical composition based on said compounds, having GR binding activity.

EFFECT: obtaining novel compounds and a pharmaceutical composition based on said compounds, which can be used in medicine as glucocorticoid receptor modulators.

10 cl, 1 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new 4-(4-cyano-2-thioaryl)- dihydropyrimidin-2-one derivatives of formula (I), a method for preparing and using them. In formula , , both A and E mean C-R7, wherein R7 mean hydrogen, Z means O, n means the number 0,1 or 2, R1 means (C1-C6)-alkyl which may be substituted by the group hydroxy, (C1-C4)-alkoxy,(C3-C6)-cycloalkyl, phenyl or 5- or 6-member heteroaryl with two heteroatoms specified in nitrogen or sulphur, or may be substituted up to three times by fluorine, or means (C3-C6)-cycloalkyl or phenyl, R2 means hydrogen, R3 means cyano or a group of formulas -C(=O)-R8, -C(=O)-O-R8 or -C(=O)-NH2, wherein R8 means (C1-C6)-alkyl or (C3-C6)-alkenyl, R4 means methyl or ethyl, or R3 and R4 are linked to each other and together form an annulated group of formula (II), R9 means hydrogen, (C1-C6)-alkyl or (C3-C6)-cycloalkyl with (C1-C6)-alkyl may be substituted by a hydroxy group, aminocarbonylamino or (C1-C4)-acylamino, R5 means hydrogen or (C1-C6)-alkyl. The other group and radical values are specified in the patent claim.

EFFECT: compounds possess the properties of a neutrophil elastase (HNE) inhibitor and can find application in treating and/or preventing pulmonary arterial hypertension (PAH), chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pulmonary emphysema, mediated by neutrophil elastase (HNE) activity.

16 cl, 4 tbl, 10 dwg, 202 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.

SUBSTANCE: invention refers to medicine, namely paediatrics and may be used for the purpose of general health improvement in children suffering recurrent respiratory infections. The method involves the high-disperse dry sodium chloride aerosol inhalations with the halo-inhaler "Haloneb". A first generation mode providing haloaerosol at 0.5 mg/min is used in the children of 5-7 years old. The length of such treatment makes 5 minutes. A second generation mode (at 1 g/min) is used in the children of 8-14 years old for 10 minutes. Then, 10-15 minutes later the haloarosol therapy is followed by a breathing training on the basis of biological feedback using the computer hardware and software cardiopulmonological complex CHS-BOS-"BIOLOGICAL FEEDBACK". The length of the above training makes 10 min for the children of 5-7 years old, and 15 min - for the children of 8-14 years old. The therapeutic course is 10-12 daily procedures.

EFFECT: method enables reducing the recovery length in the given category of children ensured by the potentiated therapeutic effect caused by the specified regimen of the combined action of the above physical factors.

2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: powder composition for intrapulmonary administration contains particles of ciprofloxacin betaine 3,5-hydrate and an excipient. The particles have a mass median aerodynamic diameter making from approximately 1 to approximately 5 mcm; a pulmonary half-life of betaine 3,5-hydrate makes min. 1.5 h; while a roughness of the composition falls within the range of 3 to 10.

EFFECT: composition may be used to treat an endobronchial infection, such as an infection caused by Pseudomonas aeruginosa, and it is most applicable for treating mucoviscidosis.

6 cl, 8 dwg, 16 tbl, 12 ex

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