Inhalation preparation for treating respiratory diseases containing micronised salmeterol xinafoate and micronised fluticasone propionate as active substances and method for preparing it

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and pharmaceutical industry and concerns a dry powder preparation containing micronised: salmeterol xinafoate and fluticasone propionate. The preparation contains a carrier consisting of lactose of average particle size 100-120 mcm and sodium benzoate. What is also described is a method for producing the preparation.

EFFECT: formulation possesses higher percentage of a respirable fraction of the active substances.

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 spacialisation medicines, 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 thepleasure of the 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, is entered by 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 drugs 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 drugs the Ah. 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 at no seretid Multidisk company Glaxo Smith Klein pharmaceuticals (http://www.rlsnet.ru/tn_index_id_28217.htm).

The preparation contains as active substances salmeterol xinafoate (micronized) and fluticasone propionate (micronized).

to 72.5 mcg/dose (50 mcg/dose in terms of salmeterol)+100 μg/dose;

72,5 μg (50 μg in terms of salmeterol)+250 μg/dose;

72,5 μg (50 μg in terms of salmeterol)+500 mcg/dose.

Excipient: lactose monohydrate, up to 12.5 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 salmeterol xinafoate and micronized fluticasone propionate, and as the carrier is lactose with an average particle size of 100-120 microns and sodium benzo is at, with a bulk density in the range of 0.30-0.50 g/cm 3in the following content of components per dose:

Salmeterola xinafoate50 mcg to 150 mcg
Fluticasone propionate50 mcg to 1500 mcg
Lactose5 mg - 50 mg
Sodium benzoate1 mg to 10 mg

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 particles of the active component with dimensions of 0.5-5 μm was not less than 99% by mass.

This composition is a combination drug in powder form, containing salmeterola xinafoate and fluticasone propionate, which have different mechanisms of action.

Salmeterol (Salmeterol) is a beta adrenomimetic and fluticasone propionate is a glucocorticosteroid with a pronounced anti-inflammatory and anti-allergic action in the lungs. Salmeterola xinafoate prevents of bronchospasm, fluticasone propionate improves respiratory function and prevent deterioration.

Combined drug can is placed in gelatin capsules and is applied using a special device - dose inhaler dry powder, for example Inhaler CDM, firm Qualitec Industria" or container-parenteral multi-dose inhaler, for example Ziklohaler, firm "Pulimood". The drug is intended for treatment of respiratory diseases, preferably asthma or chronic obstructive pulmonary disease.

This task is also solved by a method of obtaining an inhaled drug, in which substances active substances micronizer in the planetary mill, sieved lactose with an average particle size of 100-120 microns, 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/cm3and mix all of the components when the stirring speed is 40-45 rpm for 12-16 minutes

The use of auxiliary substances (media) with a porous and rough surfaces inevitably reduces respirable fraction due to intermolecular and electrostatic interactions between the active substances and carriers. Unexpectedly, it was found that sodium benzoate in a mixture with lactose taken in certain quantities reduces such interaction.

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

In the study of mixtures acceptable carriers, detecting the life, a mixture of lactose and sodium benzoate, 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 or just benzoate. Specific values for respirable fractions (measured by fluticasone the propionate, 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.

Tests.

The preparation obtained by the above technology and the control 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 Americas is nskoi 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. Test results of various drugs on the respirable fraction and the results of the effectiveness of these drugs in medical practice, we can assess the magnitude of respirable fraction: 15% -fair, 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.

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

Example 1

Salmeterola xinafoate 50 mcg;

Fluticasone propionate 50 mcg;

Lactose 5 mg;

Sodium benzoate 10 mg

Respirable fraction 34,2%

The micronization of the active substances is carried out in a planetary melni the e company Retsch, PM 400 to obtain a powder in which the proportion of particles with sizes of 0.5-5 μm amounted to 99.6% by weight. Lactose with an average particle size of 100-120 μm (for example, Inhalac®, 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. 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 in the range of 0.38 to 0.44 g/cm3. The mixing is carried out in the framework mixer at 500 g product with balls of stainless steel with a diameter of 9 mm, a weight of 2.25 kg Initially load ½ of the required number sieved lactose. Then download substance and sodium benzoate, and 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 mnogochasovykh Inga is atarov, or other devices for inhalation.

Example 2

Salmeterola xinafoate of 72.5 mcg;

Fluticasone propionate 100 mcg;

Lactose 10 mg;

Sodium benzoate 2 mg

Respirable fraction 43,1%

Receiving inhalation of the drug are similar to example 1, but the proportion of micronized particles of the active component with dimensions of 0.5-5 μm is 99% by mass, bulk density sifted sodium benzoate is in the range of 0.30 to 0.44 g/cm3. Mixing lead with a speed of 40 rpm for 12 minutes

Example 3

Salmeterola xinafoate of 72.5 mcg;

Fluticasone propionate 250 mcg;

Lactose 10 mg;

Sodium benzoate 2 mg

Respirable fraction 47,4%

Receiving inhalation of the drug are similar to example 1, but the proportion of micronized particles of the active component with dimensions of 0.5-5 μm is 99,8% by weight, the bulk density of sifted sodium benzoate is in the range of 0.44-0.50 g/cm3. Mixing lead with a speed of 45 rpm for 16 minutes

Example 4

Salmeterola xinafoate of 72.5 mcg;

Fluticasone propionate 500 mcg;

Lactose 10 mg;

Sodium benzoate 2 mg

Respirable fraction of 45.6%

In examples 4-8 receiving the drug are similar to example 1.

Example 5

Salmeterola xinafoate 100 mcg;

Fluticasone propionate 1000 mcg;

Lactose 50 mg;

Sodium benzo is t 1 mg

Respirable fraction of 36.4%

Example 6

Salmeterola xinafoate 150 mcg;

Fluticasone propionate 1500 mcg;

Lactose 10 mg;

Sodium benzoate 5 mg

Respirable fraction of 33.8%

Example 7

Salmeterola xinafoate of 72.5 mcg;

Fluticasone propionate 250 mcg;

Lactose 12.5 mg;

Sodium benzoate 5 mg

Respirable fraction 30,8%

Example 8 (comparative)

Salmeterola xinafoate of 72.5 mcg;

Fluticasone propionate 250 mcg;

Sodium benzoate 50 mg;

Respirable fraction 8%.

This invention improves the efficiency of the drug due to the higher content of respirable fraction of the active substances.

1. Inhalation drug for treating respiratory diseases comprising as active substances micronized salmeterol xinafoate and micronized fluticasone propionate and the media, wherein the media it contains lactose with an average particle size of 100-120 microns and sodium benzoate with a bulk density in the range of 0.30-0.50 g/cm3in the following content of components per dose:

Salmeterola xinafoate50 mcg to 150 mcg
Fluticasone propionate50 mcg to 1500 mcg
Lactose5 mg - 50 mg
Sodium benzoate1 mg to 10 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 μm is not less than 99 wt.%.

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 way to obtain a pharmaceutical preparation according to any one of claims 1 to 3, characterized in that micronizer active substances in the planetary mill, sieved lactose with an average particle size of 100-120 microns, sift sodium benzoate to obtain a bulk density in the range of 0.30-0.50 g/cm3, mix all of the components when the stirring speed is 40-45 rpm for 12-16 minutes



 

Same patents:

FIELD: medicine.

SUBSTANCE: hyaluronidase immobilised on polyethylene glycol is introduced into laboratory animals intranasally in a dose of 16 units. Hyaluronidase is introduced once a day on 1st, 3rd, 7th and 10th day after administering bleomycin that is a pulmonary fibrosis simulation factor.

EFFECT: higher pulmonary tissue resistance to fibrotic depositions, including prevents a reverse process of fibrosis formation ensured by the properties of pegylated hyaluronidase and developed mode of its administration that leads to a prolonged antifibrotic effect with low toxicity and immunogenicity of the effects on the body.

1 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: there are presented: a liposomal preparation for the pulmonary delivery, wherein the liposomes a surface of which is modified by at least one polymer specified in a group consisting of terminally hydrophobisated polyvinyl alcohols and chitosan, an encapsulated gene, a method for preparing and a method of treating a pulmonary tissue disease involving the stage of administering the above liposomal preparation into the patient's lung. It has been shown that the liposome modified by terminally hydrophobisated polyvinyl alcohol may be kept on the pulmonary tissue surface for a long time.

EFFECT: high effectiveness of the pulmonary delivery of the claimed liposomal preparation for a relatively short time.

10 cl, 1 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to dry powder-like pharmaceutical composition for inhalation and to method of its obtaining. Into composition of pharmaceutical composition included are two active ingredients, which represent salmeterol and fluticasone or their pharmaceutically acceptable salts, solvates or esters, two pharmaceutically acceptable excipients, which have value d50 respectively approximately 125-145 mcm and approximately 50-100 mcm and which represent mono- or disaccharides. Method of composition obtaining consists in formation of preliminary mixtures of each of active ingredients and each of pharmaceutically acceptable excipients and mixing two preliminary mixtures with obtaining with fraction of medication, with weight ratio of exipients in said two preliminary mixtures constituting from 1 to 5.

EFFECT: pharmaceutical composition is applied for treating asthma, COLD (chronic obstructive lung disease), allergies and infectious diseases.

6 cl, 7 dwg, 3 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new alkylthiopyrimidines of formula III or pharmaceutically acceptable salts thereof: In the compound III X represents a direct bond; R2 means hydrogen, halogen, (C1-C6)alkyl, (C3-C7)cycloalkyl, -NR8aR8b or the group -SR3; each R3 independently represents (C1-C6)alkyl, optionally mono-, di- or trisubstituted by halogen; or (C3-C7)cycloalkyl; R4a and R4b represent hydrogen; R6 represents aryl; or heteroaryl; wherein aryl and heteroaryl are optionally substituted in a substituted position by one or more substitutes specified in a group consisting of (a) halogen; (b) cyano; (c) nitro; (a) hydroxy; (e) guanidino; (f) heteroaryl; (g) phenyl; (h) phenyloxy; (i) benzyl; (j) benzyloxy (k) -NR8aR8b; (1) -C(O)R9; (m)-C(O)NR8aR8b, (n) - OC(O)NR8aR8b; (o) -C(O)OR9; (p) -NR7C(O)0R9; (q) -NR7C(O)R9; (r) sulphamoyl; (s) (C1-C6) alkylsulphonyl; (t) (C1-C6)alkylaminosulphonyl; (i) di(C1-C6)alkylaminosulphonyl; (v) (C1-C6)alkyl, optionally mono-, di- or trisubstituted by halogen; (w) (C1-C6) alkoxy, optionally mono-, di- or trisubstituted by halogen; and (x)(C1-C6)alkylthio, optionally mono-, di- or trisubstituted by halogen R7 represents hydrogen. The other radical values are specified in the patent claim.

EFFECT: compounds possess CRTH2 (G-protein related chemoattractant receptor expressed on Th2 cells) antagonist activity and are applicable for treating and preventing the diseases related to CRTH2, including treating allergic diseases, eosinophil and basophile related diseases.

14 cl, 6 dwg, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutics, namely to a composition for preventing and/or treating respiratory pathologies and/or infections and for improving intestinal functions. Using a symbiotic composition for preparing a drug preparation for preventing and/or treating the respiratory pathologies and/or infections. The symbiotic composition containing an active ingredient presented by a) a mixture containing the following bacterial strains: Lactobacillus plantarum LMG P-21020; Lactobacillus plantarum LMG P-21021; Lactobacillus rhamnosus DSM 16605; Lactobacillus rhamnosus DSM 19739; Bifidobacterium lactis LMG P-21384 and b) a prebiotic ingredient containing at least one scFOS (short-chain fructooligosaccharide) or GOS (galactooligosaccharide).

EFFECT: using the declared method enables more effectively preventing and/or treating the respiratory pathologies with simultaneously improving and/or controlling the intestinal functions.

11 cl, 2 tbl, 2 ex

FIELD: biotechnologies.

SUBSTANCE: invention relates to derivatives of aminopyrazol with the formula of , where A, E, R1 and R2 have values specified in the invention claims, and to their pharmaceutically acceptable salts. Compounds of the formula (I) are agonists of the ALX receptor. Besides, the invention relates to a pharmaceutical composition on the basis of the compound of the formula (I) or its pharmaceutically acceptable salt and to application of these compounds for production of a medicinal agent for prevention or treatment of a disease selected from inflammatory diseases, wheezing diseases, allergic states, HIV-mediated retrovirus infections, cardiovascular diseases, neuroinflammations, neurological disorders, pain, prion-mediated diseases and amiloid-mediated diseases; and for modulation of immune responses.

EFFECT: higher efficiency of compound application.

23 cl, 1 tbl, 466 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely oncology and radiology, and may be used for treating radiation-induced lung injuries complicated by the abscess formation. That is ensured by using anti-inflammatory agents such as corticosteroids, antibiotics, and inhalation of 10% dimethyl sulphoxide; bronchodilators, mucolytics, antiplatelet, antihistamines, antitussives, breathing exercises and oxygen therapy. In this case, the treatment is performed in hospital environment and combined with using detoxification, analgesic, hemostatic agents and antitussives, controlled hypotension, abscess cavity sanitation; the above aids are used till pain management, body temperature normalisation, general status stabilisation, cough and dyspnea relief. Then, replacement, metabolic, reparative and immune agents are prescribed additionally. The treatment is continued until the Karnovskiy functional status is stabilised at 60-80%, while decreasing the amount of the abscess cavity discharge by 50% or the absence; in this case the patient is transferred to the outpatient treatment with regular admission when the Karnovskiy status is occurred to decrease to 40-50%, while the QOLi-NS value decreases to 25 points, and an X-ray pattern seem to alternate.

EFFECT: invention provides the conservative treatment of complicated radiation-induced lung injuries; it enables prolonging the life and quality thereof in the patients suffering radiation-induced purulent-destructive chest processes.

23 cl, 6 dwg, 2 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention provides to a high degree a safe pharmaceutical drug which is effective for diseases caused by MMP-2 and/or MMP-9. The pharmaceutical drug contains, as an active ingredient, at least one member selected from a group which consists of thiazole derivatives of formula (1): where R1 is a phenyl group which can have 1-3 lower alkoxy groups as substitutes in the phenyl ring, and R2 is a pyridyl group which can have 1-3 carboxyl groups as substitutes in the pyridine ring, or salts thereof.

EFFECT: high activity and use when treating diseases such as fibrosis and pulmonary emphysema.

4 cl, 4 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I), stereoisomers, trans- and cis-isomers, racemates or pharmaceutically acceptable salts thereof, having modulating activity on histamine H3-receptors. In formula (I) m equals 0; one of R1 and R2 is selected from a group which includes hydrogen, C1-10alkoxycarbonyl, amido-, carboxy-, C3-8cycloalkyl, halogen, -NRARB, (NRARB)carbonyl, or a group of formula -L2-R6; the other of R1 and R2 is selected from a group which includes hydrogen, halogen; each of R3a and R3b is independently selected from a group which includes hydrogen; each of R4 and R5 is independently selected from a group which includes C1-10alkyl and C1-10hydroxyalkyl; or R4 and R5, taken together with a nitrogen atom to which each is bonded, form a heteroaromatic ring of the type (a) or (b), where Q1 is O or C; Q2 is -N(R20)-; R20 is selected from a group which includes hydrogen and C1-10alkoxycarbonyl; each of p1 and p2 is independently equal to 1, 2 or 3; each of q1, q2, q3, q4 and q5 are independently equal to 0, 1 or 2; and wherein each carbon atom in the ring is substituted with hydrogen or 0, 1 or 2 substitutes, independently selected from a group which includes hydrogen, hydroxy group, fluorine, C1-10alkyl, C1-10hydroxyalkyl and C1-10fluoroalkyl; R6 is a phenyl, heterocycle or heterocycloC1-4alkyl, wherein the heterocycle is a 4-6-member aromatic or non-aromatic ring which contains 1 or 2 heteroatoms independently selected from N, O and S, optionally condensed with a benzene ring, wherein the phenyl or heterocycle can be unsubstituted or optionally substituted with one or more substitutes independently selected from a group which includes C1-4alkoxy, C1-4alkyl, cyano, halogen and oxo-; L is a bond or C1-4alkylene; L2 is a bond, C1-4alkylene, -C(=O)-, -SO2N(R14a)-, -N(R14a)SO2-, -C(O)N(R14a)-, -N(Rl4a)C(O)- or -N(R15)-; R10 is selected from a group which includes hydrogen; R14a is selected from a group which includes hydrogen; R15 is selected from a group which includes hydrogen; and RA and RB are independently selected from a group which includes hydrogen, C1-10alkyl, C1-10acyl, C1-4halogenalkyl, C1-10alkoxycarbonyl, C3-8cycloalkyl and C3-8cycloalkylcarbonyl. The invention also relates to a pharmaceutical composition which contains compounds of formula (I), a method for selective modulation of effects of histamine H3-receptors, use of said compounds in producing a medicament for treating a condition or disorder modulated by histamine H3-receptors, as well as specific compounds of formula (I).

EFFECT: improved properties of compounds.

18 cl, 2 tbl, 154 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrimidine derivatives of formula (I) in free form or in form of a pharmaceutically acceptable salt or solvate, which are useful in treating inflammatory or obstructive airways, pulmonary hypertension, pulmonary fibrosis, liver fibrosis, muscle diseases and systemic skeletal disorders and other diseases which are mediated by activity of the ALK-5 receptor or ALK-4 receptor. The invention also relates to a method of producing compounds of formula (I) and pharmaceutical compositions. In formula , T is a pyridin-2-yl which is optionally substituted in one position with R1; T1 is a pyridinyl which is optionally substituted in one or two positions with R1, R2, R5, C1-C4-alkoxy group, C1-C4-alkoxycarbonyl or cyano group; and Ra and Rb are independently hydrogen; C1-C8-alkyl, optionally substituted in one, two or three positions with R4; C3-C10-cycloalkyl, which is optionally substituted in one or two positions with a hydroxy group, amino group, C1-C8-alkyl, C1-C8-alkoxy group, halogen, cyano group, oxo group, carboxy group or nitro group; or C6-C15-aryl, optionally substituted in one, two or three positions with a halogen, hydroxy group, amino group, cyano group, oxo group, carboxy group, nitro group or R5; R1 is C1-C8-alkyl; R2 is C6-C15-aryl, optionally substituted in one, two or three positions with a halogen, hydroxy group, R1, R5, C1-C8-alkylthio group, amino group, C1-C8-alkylamino group, etc. The rest of the values of the radicals are given in the claim.

EFFECT: high efficiency of using said compounds.

20 cl, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to dry powder-like pharmaceutical composition for inhalation and to method of its obtaining. Into composition of pharmaceutical composition included are two active ingredients, which represent salmeterol and fluticasone or their pharmaceutically acceptable salts, solvates or esters, two pharmaceutically acceptable excipients, which have value d50 respectively approximately 125-145 mcm and approximately 50-100 mcm and which represent mono- or disaccharides. Method of composition obtaining consists in formation of preliminary mixtures of each of active ingredients and each of pharmaceutically acceptable excipients and mixing two preliminary mixtures with obtaining with fraction of medication, with weight ratio of exipients in said two preliminary mixtures constituting from 1 to 5.

EFFECT: pharmaceutical composition is applied for treating asthma, COLD (chronic obstructive lung disease), allergies and infectious diseases.

6 cl, 7 dwg, 3 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: dry powder composition for pulmonary inhalation Parkinson's disease contains apomorphine and magnesium stearate with a nominal dose of apomorphine being 3 to 10 mg and providing a dose of fine particle fraction (FPF) making 2 to 6 mg when administered. A method for preparing the composition involves the stages of combining the apomorphine particles with the magnesium stearate particles by mixing and milling, milling including compression.

EFFECT: composition under the invention contains apomorphine in a stable dry powder form suitable for the direct administration of low doses of the drug with minimal adverse side effects.

15 cl, 12 dwg, 13 tbl, 12 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to medicine and describes a solution for producing an inhalation preparation containing fenoterol hydrobromide as an active agent, purified water and excipients with the excipients presented by sodium benzoate, an acidity regulator representing an organic acid in the following proportions, mg/ml: fenoterol hydrobromide 1.0-1.1; sodium benzoate 0.2-2.0; organic acid 1.4-1.7; purified water the rest provided pH makes 3.2-3.5.

EFFECT: solution has the high value of respirable fractions and high stability.

6 cl, 3 ex

FIELD: tobacco industry.

SUBSTANCE: imitative smoking device (1,51) contains an imitative cigarette having an essentially cylindrical cigarette-like shape and a charging unit (2, 50) having an essentially rectangular body shaped like a cigarette packet. The filling device (2, 50) contains charging gas (32, 59) for the imitative cigarette and a means for elective retention of the imitative cigarette. The imitative cigarette may be completely retained inside the body (3, 52). The cigarette may be retained at a place other than the charging place. A dose counter may be envisaged to give visual indication of doses in the charging device.

EFFECT: technical result achieved using the imitative cigarette device and the charging device for the imitative device according to the invention consists in smoking skill imitation, the imitative cigarette charging and its usage simplification.

7 cl, 15 dwg

FIELD: medicine.

SUBSTANCE: there are disclosed method and composition for intensifying mucus excretion and treating pulmonary disorders, such as cystic fibrosis. They use together with osmotically active substance a synthetic pulmonary surfactant containing one or more pharmaceutically acceptable phospholipids mixed with SP-B polypeptide or its fragment, or polypeptide containing at least 10 amino acid residues and no more than about 60 amino acid residues, said polypeptide containing a sequence having variable areas of hydrophobic and hydrophilic amino acid residues presented by formula (ZaUb)cZd, wherein surfactant activity of mixed phospholipids and polypeptide higher than that of one phospholipid, has osmolarity varying between 220-1200 mOsm/kg, the concentration of free anions varying between 20-200 mmole/l and the pH value varying between 6.8 and 8.0, and the surfactant provides the pulmonary delivery of a daily dose varying between approximately 20 and 200 mg of total phospholipid equivalent.

EFFECT: invention provides intensified mucus excretion and improved quality of life in the patients suffering cystic fibrosis, bronchitis, bronchiectasis, ciliary diskinesia, COPD, or sinusitis.

15 cl, 2 dwg, 4 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medicine, namely pharmacology. A pharmaceutical composition contains an active component selected from a group of pharmacologically active substances: having an effect on a central nervous system, peripheral neurotransmitter processes, cardiovascular system, coagulation system, neoplastic processes, metabolic processes, showing antibacterial activity, an excipient, cyclodextrin as a component ensuring high bioavailability, and a component modulating a duration of the pharmacologically active substance representing polymer. The pharmaceutical composition is presented in the form of a powder of particle size within 0.4 to 2 mcm. A method for administration of the pharmaceutical composition provides the pulmonary oral administration in the form of a dry or liquid aerosol with mass median aerodynamic diameter 0.8 to 2.0 mcm and degree of polydispersity 0.8 to 2.0.

EFFECT: ensured effective delivery of the pharmacologically active substances in the systemic circulation and alveolar inhalations of min 75% of solid or liquid aerosol particles.

5 cl, 5 dwg, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: declared invention refers to chemical-pharmaceutical industry, and concerns new, taste-masking powders specified in a group consisting of biologically active substances for treating, relieving and preventing diseases in humans and animals, with average particle diameter d50 1 to 40 mcm and coating thickness 1 to less than 20 mcm of a hydrophobic coating material containing 50 to 90 wt % (relative to total powdered solid substance and coating material) with the hydrophobic coating material being wax of fusion temperature within 30 to 180°C, resin, polymethacrylate or its copolymer for inhalation or oral administration.

EFFECT: what is offered is a simple method for preparing and applying them for introducing the biologically active substances.

10 cl, 3 ex

FIELD: medicine.

SUBSTANCE: as an active substance, an aerosol contains aprotinin taken in the amount 23 to 30 mg in 100 ml of the preparation; a propellant is 1,1,1,2-tetrafluoroethane 70-84 vol. %; the solvents are ethanol 8-15 vol. %, glycerine 5-10 vol. %, water and a stabiliser is peppermint oil. The aerosol is pressurised in an aerosol container with a measuring valve.

EFFECT: preparation under the invention preserves native use and long storage antiprotease and antiviral properties of aprotinin.

6 cl, 2 tbl

FIELD: medicine; pharmaceutics.

SUBSTANCE: application of an antidepressant for manufacture of a medical product in the form of a dry powder for treatment of premature ejaculation, the corresponding way of treatment, an inhaler of dry poropps, containing a medical product of an antidepressant and a blister with an antidepressant (for example, tricyclic clomipramine depressant) for application in an inhaler of a dry powder are offered. The invention provides achievement of therapeutic effect during not more than 20 minutes at reduction of a dose and by-effects (in comparison with peroral intake of antidepressants). Thus bond deposition in a drink was less than 10%.

EFFECT: acceleration of achievement of therapeutic effect.

30 cl, 3 dwg, 3 tbl

FIELD: medicine.

SUBSTANCE: invention refers to chemical-pharmaceutical industry, and concerns pharmaceutical composition of metered aerosols containing antiasthmatic agents in the form of suspensions, solutions and emulsions. The metered aerosols are characterised with improved pharmaceutical properties and high storage stability. The pharmaceutical composition of metered aerosols containing antiasthmatic agents in the form of suspensions, solutions and emulsions, contains therapeutically effective amounts of Salbutamol or its salts, or formoterol fumarate or budesonide or beclomehasone dipropionate, propellent R 134A and target additives including ethyl alcohol, glycerine, isopropyl myristate, Tween 80, water.

EFFECT: suitable for treatment of various obstructive pulmonary diseases such as bronchial asthma, bronchitis, pneumonia etc.

4 cl, 12 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to dry powder-like pharmaceutical composition for inhalation and to method of its obtaining. Into composition of pharmaceutical composition included are two active ingredients, which represent salmeterol and fluticasone or their pharmaceutically acceptable salts, solvates or esters, two pharmaceutically acceptable excipients, which have value d50 respectively approximately 125-145 mcm and approximately 50-100 mcm and which represent mono- or disaccharides. Method of composition obtaining consists in formation of preliminary mixtures of each of active ingredients and each of pharmaceutically acceptable excipients and mixing two preliminary mixtures with obtaining with fraction of medication, with weight ratio of exipients in said two preliminary mixtures constituting from 1 to 5.

EFFECT: pharmaceutical composition is applied for treating asthma, COLD (chronic obstructive lung disease), allergies and infectious diseases.

6 cl, 7 dwg, 3 tbl, 3 ex

Up!