Dosage form containing desloratadine and method for producing it

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, particularly to pharmaceutical industry, and describes a tabletted oral dosage form containing desloratadine in an amount of 3 to 15%, processing additives and a pharmaceutically acceptable excipient. The processing additives consist of sodium croscarmellose, magnesium stearate and povidone. The excipient represents a mixture of lactose disaccharide and microcrystalline cellulose polysaccharide in ratio from 2:1 to 8:1. Lactose and microcrystalline cellulose have an average particle size from 30 to 200 mcm. Producing the table involves granulating desloratadine, lactose and microcrystalline cellulose.

EFFECT: invention provides reducing granulate compression force, increasing process capability and maintaining the high quality of the tablets.

9 cl, 4 tbl, 4 ex

 

The invention relates to medicine, in particular to the pharmaceutical industry, and describes oral pharmaceutical composition is in tablet form comprising desloratadine and its manufacturing method.

In recent years, worldwide there is a significant increase of allergic diseases. Allergic diseases suffers every tenth inhabitant of the Earth, and in some regions - one in six. According to official statistics in Russia suffers from allergic diseases 10 to 15% of the population. According to who, allergic diseases are the 3 most common cancer. Over the last decade there has been a doubling in the incidence of allergic rhinitis, bronchial asthma, atopic dermatitis.

In this regard, today, it is extremely important to establish effective, high-quality and affordable anti-allergic pharmaceutical compositions and ensuring high technology and performance of their production.

One of the most effective active ingredients to eliminate allergic symptoms of various etiologies is desloratadine. Chemical name of desloratadine - 8-chloro-6,11-dihydro-11-(4-piperidinylidene)-5H-benzo[5,6]cyclohepta[1,2-b]pyridine.

Desloratadine belongs to a group of blockers HI-pickling stone inovah receptors snapshot length�th operation, is an antihistamine of the third generation. Desloratadine inhibits the release of histamine and leukotriene C4 from mast cells prevents the development and facilitates the allergic reactions, has anti-allergic, antipruritic and pretioase dative effect, reduces the permeability of capillaries, prevents the development of tissue edema, relieves smooth muscle spasm.

One of the main features of desloratadine is its high selectivity and minimal risk of adverse reactions. This active metabolite of loratadine is characterized by the highest affinity for H1-receptors is 200 times larger than Fexofenadine, 50 times larger than loratadine and cetirizine and 3 times greater than that of levocetirizine. So desloratadine is stronger inverse agonist H1-receptors, which is proven in clinical studies and in medical practice (J. Anthes, Richard S., R. West et al. Functional characteristics of desloratadine and other anhistamines in human Y1 receptors. Allergy, 2000, 55 (suppl. 63), S279 (Abstract 994); Henz V. The pharmacological profile of desloratadie: a review. Allergy, 2001, 56 (suppl. 65), 7-13.).

In particular, in a randomized double-blind placebo-controlled studies of desloratadine in allergic rhinitis for about 1 thousand patients was proved to be superior to desloratadine placebo and reduces all major sympto�s rhinitis, including nasal congestion. Found that desloratadine is almost the only blocker of H1-histamine receptors, demonstrating in controlled studies permanent decongesting effect. Desloratadine can be used to treat both seasonal and non-seasonal allergies with reactions to house dust, feathers, pollen, dander, various food allergens. In addition, in blind placebo-controlled multicenter studies have confirmed the effectiveness of desloratadine in chronic idiopathic urticaria (R. Lorber, Salmun, L., M. Danzig Desloratadine is effective at relieving nasal congestion, as demonstrated in three placebo-controlled trials in patients with seasonal allergic rhinitis. New Trends in Allergy V meeting, Davos, 2000; Nathan R. and the Desloradine Study Group. Desloratadine relieved nasal congestion in patients with seasonal allergic rhinitis. Annual meeting of American College of Allergy, Asthma and Immunology, Seattle, 2000.).

Desloratadine has not only antihistamine effect, as well as anti-inflammatory and anti-allergic. He also blocked a number of other mediators involved in the development of systemic allergic inflammation. Also, the drug reduces the permeability of capillaries, prevents the development of tissue edema.

In addition, desloratadine has no sedative effect, when taken in therapeutic doses does not affect the speed of psychomotor reactions and enhances the inhibitory effect of ethanol on psychoma�ornago function. Desloratadin determined in plasma after 30 minutes after taking, period floor removal reaches 21-24 hours. The meal has no significant effect on the absorption of the drug. Therefore, the drug can be taken 1 time/day regardless of the meal.

Thus, desloratadine significantly improves the quality of life of patients with allergic diseases, and, as shown by population studies, even in cases where previous treatment with other antihistamines is ineffective.

First formula of desloratadine and its salts, process for its preparation and pharmaceutical composition with desloratadine as active substances, have been described in the patent US 4659716 with priority from 15.02.1984 it was the inventive method and composition of the dosage form. The active substance is mixed with carrier having the necessary binding properties in suitable proportions and pressed into the desired shape and size. Powders and tablets are in this case preferably contain from 5 to 20 percent active ingredient. The fillers preferably are used: magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, methylcellulose, sodium carboxymethylcellulose, low melting wax, cocoa butter, etc.

From predshestvuyuschih� the prior art as well known and applicable antihistamine formulations comprising from 5 to 50 mg of desloratadine or pharmaceutically acceptable salts.

In particular, the known formulations of the drugs Largestin (Registration certificate № LSR-006570/10 registration date: 09.07.2010), Desloratadine Canon (Registration certificate № LP-001853 registration date: 27.09.2012), Desloratadine Teva (Registration certificate № LP-001627 registration date: 06.04.2012) and others. These drugs are introduced in the market in the form of tablets, film-coated, tablets for sucking and syrups.

The best-known drug containing Desloratadine and widely available on the market is the Aerius® (Registration certificate № P N014704/02, date of registration 06.08.2010), made in the form of tablets, film-coated, tablets for sucking and syrups. These tablets are film-coated and contain the following components, mg:

Componentsmg
Desloratadine5
Calcium hydrophosphate dehydrate53
Microcrystalline cellulose28
Corn starch 11
Talc3
Shell (Opadry blue, Opadry6,61
transparent, wax carnabucci, wax
bee white)
Total106,61

Describing briefly the solid dosage form such as tablets, the drug is usually manufactured by extrusion of a suitable granulate in the desired solid dosage form, wherein the granulate consists of the desired components in the form of a mixture of solid particles. Usually such particles are therapeutically active ingredient, different excipients (fillers, disintegrating agents, lubricants and binders, perhaps in conjunction with, for example, Corrigendum, preservative and/or dye. Commercially available tablets Aerius® is made in accordance with the common Protocol, and this tablet was first disclosed, as described in the patent US 4659716, the essence of which is included in this description by reference.

Tablet Aerius®, presents currently on the market and, thus, produced in industrial scale, comprises a therapeutically Akti�nogo ingredient of desloratadine with calcium hydrophosphate, the microcrystalline cellulose as excipients and, accordingly, a suitable amount of binder and lubricating substance.

Any compaction of the granules consisting of a mixture of solid particles in tablets, there is a General need in the implementation of the pressing operation with the highest possible speed while minimizing, at the same time wear of the mechanism and to obtain tablets of a quality that meets regulatory requirements.

Currently there is a need to develop more accessible and easy to manufacture drugs desloratadine with high chemical and physical stability during storage, corresponding to the modern requirements for quality, made preferably in the form of solid dosage pharmaceutical forms, qualitative and quantitative composition of which ensures high performance, manufacturability with concurrent low production cost, but also expand the Arsenal of anti-allergic drugs of domestic production.

Discovered that the combination of certain proportions of the disaccharide is lactose with polysaccharide - cellulose microcrystalline, taken with a certain particle size of these excipients, unexpectedly provides a significant speed increase in the percent�CoE manufacturing while the wear mechanism and the quality of the tablets remain essentially unchanged compared with the industrial processes used to date. Essentially, the ratio of components and the size of the particles, referred to, apparently, affects the flowability of the granulate particles and their relative position in the tablet during and after pressing, so that provides increased overall performance and, consequently, the speed of the process of manufacturing a preformed drug, desloratadine, and allows to obtain tablets with sufficient mechanical strength while using less tonnage, which saves energy.

In modern industrial presses performed a bilateral compression of the powder in the matrix between the two punches. Researchers believe that the mechanical connection in the tablet due to the size of the contacting surfaces, as well as interweaving and the engagement surface of the protrusions and irregularities of the particles under pressure. As a result of applied pressure, the particles can shift and slide against each other and come into closer contact; symmetric glide easier than rough, but the latter creates a greater number of links and therefore give a compressed tablet of a higher strength�. Thanks to an experimental selection of components, the particles of which possess the above properties in an optimal process for high-performance extrusion ratios, the inventors were able to solve the task.

More specifically the present invention relates to pharmaceutical compositions in the form of a solid dosage form containing desloratadine or its pharmaceutically acceptable salts as therapeutically active ingredient together with pharmaceutically acceptable excipients, diluent or carrier, or a mixture thereof, where at least one of a specified set of excipient, diluent and carrier in the most preferred embodiment is a disaccharide, more preferably lactose, and the other in the most preferred embodiment is a polysaccharide, more preferably microcrystalline cellulose, wherein the average particle size of these substances is in the range from 30 to 200 μm. Moreover, the mass ratio of lactose and microcrystalline cellulose is from 8:1 to 2:1, and the amount of therapeutically active substance, from 3 to 15%.

Proper use and understanding of terms excipient, diluent, carrier requires no explanation and is completely within the qualification of specialist in the manufacture�Oia pharmaceuticals.

The pharmaceutical composition of the present invention may contain at least one additive selected from a disintegrant, a lubricant, a binder, corrigenda, preservative, dye, and mixtures thereof. Where appropriate, you can also include other additives. Typical examples of disintegrants, lubricants (e.g., magnesium stearate), binders (e.g., povidone), corrigentov, preservatives and dyes, and suitable mixtures thereof, as well as any other traditional supplements that can be considered a specialist in this field, engaged in the practice of the present invention can be found in "Handbook of Pharmaceutical Excipients"; Ed. A. H. Kibbe, 3rdEd., American Pharmaceutical Association, USA and Pharmaceutical Press UK, 2000, the essence of which is included in this description of the invention. As an example, also applicable in the practical implementation of the present invention, it may be mentioned that the normal amount of lubricants and binders, as well as other traditional technological additives are in the order of less than 10% by weight of the pharmaceutical composition.

The composition of the commercially available tablets, manufactured used to date ways, suitable diluents include calcium hydrogen phosphate, starch, microcrystalline cellulose. Such a composition after the manufacture thereof granulate iliskisi, does not allow the pressing speed in excess of 120,000 tablets per hour on a single rotary press with 45 press set. Compared to this method of the present invention allows to obtain the speed of extrusion to approximately 200000 pills/h inclusive with the desired quality pills and low level of wear tabletiruemogo mechanism.

In a preferred embodiment of the specified pharmaceutical composition, the average particle size is in the range from 30 to 200 μm. In another preferred embodiment the average particle size is in the range from 90 to 180 μm. In an additional preferred embodiment of the specified average particle size of the lactose is in the range from 150 μm to 200 μm, and microcrystalline cellulose from 70 to 110 μm. In the most preferred embodiment of the present invention the specified average particle size for the lactose is 70-80 μm and microcrystalline cellulose 40-60 microns (measured using sieves using air jets).

When measuring the particle size using sieves using air jets the air is blown through the sieve up from the rotating slit so that the residue on the sieve becomes fluidized. At the same time to the bottom of the sieve exert a negative pressure which removes fine particles in the FDS�Rai device. Analyses of the size and determination of the average particle size is carried out by removal of particles from the end of the small particles in the size distribution sequentially using a single sieve. For additional details, see also in "Particle Size Measurement", 5thEd., p 178, vol.1; T. Allen, Chapman & Hall, London, UK, 1997. For the person skilled in the art such measurement size, therefore, is traditional.

In a preferred embodiment the pharmaceutical compositions are present as specified disaccharide, and polysaccharide. In this particular embodiment the mass ratio of said disaccharide and polysaccharide is usually from 8:1 to 2:1, preferably 7:1 to 4:1 and more preferably from 6:1 to 5:1.

The total number of these excipient, diluent and carrier in combination is usually from 75 to 96%, preferably from 80% to 90% by weight of the pharmaceutical composition, and the remaining part to 100% inclusive is a therapeutically active ingredient together with the aforementioned additives, where the latter preferably represent lubricity, retryplease and binder.

These relations share components and dimensions of the particles, determined experimentally and can be justified as follows. Lactose is a crystalline powder, and cellulose, microcar�metal possesses both the properties of the fibers and crystalline powder. Particles of lactose to provide a mixture of fluidity and slipping particles during the compaction, the particles of microcrystalline cellulose increase the area of the contacting surfaces.

If you increase the ratio of lactose: microcrystalline cellulose more than 8:1, the pressing process to achieve sufficient strength must flow at high pressure and low speed, while lower than 2:1, decreases the fluidity of the mixture and the bulk density to such an extent that there may be problems with the accuracy of dosing of the powder weight in the matrix during high-speed compression. There is no doubt that the pressing process is also influenced by the presence in the mixture of the active substance. The inventors have experimentally determined the limits of the content of desloratadine from 3 to 15%. Moreover, the lower limit of 3% is not due to the properties of the powder to be subjected to high compression, and the fact that tablets containing an acceptable amount of desloratadine is not economically expedient to enter into the composition of more than 97% thinners.

Pharmaceutical composition in the form of solid dosage forms of the present invention typically is a tablet suitable for oral administration. Such tablet may be coated.

The composition typically contains desloratadine in black�the number from 3 to 50 mg per unit dosage forms. As an example: a typical tablet containing 5 mg of desloratadine, is white or nearly white, cylindrical, biconvex shape with a diameter of 6 mm and weight of 95 mg.

Accordingly, an additional aspect of the present invention relates to a method of manufacturing a pharmaceutical composition in the form of a solid dosage form that contains desloratadine as a therapeutically active ingredient comprising stages on which:

1) mix desloratadine and excipient, diluent or carrier, or mixtures thereof, possibly in the presence of a wetting agent, where at least two of said excipient, diluent and carrier is a lactose and microcrystalline cellulose, wherein the average particle size for the lactose is 70-80 μm and microcrystalline cellulose 40-60 microns

2) shaping the resulting mixture is granulated, possibly in the presence of a wetting agent, suitable for pressing into a specified solid dosage form;

3) may carry out the specified mixing and/or formation of a granulate in the presence of at least one additive selected from a disintegrant, a lubricating agent, a bonding agent, corrigent, preservative, dye, and mixtures thereof;

4) maybe specified dried granulate;

5) extrude the said granulate in the solid Lekarstvo�th form.

6) may be applied on the specified solid dosage form membranous sheath.

A method according to the present invention as such can be implemented by using conventional equipment for the manufacture of pharmaceutical products, as defined and specific components. The granulate suitable for compression into tablets, usually has the average size of the granules is at least about 100 microns. Individual granules with a size of more than 2 mm usually do not transfer to the next stage of compression.

As non-limiting examples, you can specify the following equipment for pelletizing: solid fluidized layer and direct heating, for example supplied by GEA/Collette NV, BE (series UltimaPro™), Huttlin GmbH, DE (HDG series), Diosna Dierks&Soehne GmbH, DE (VAC series), Fluid Air Inc., US (series Magnaflo®) and Vector Corp., US (GMX series); with a moving rigid layer and an indirect heat exchange comprising a blade system, rotary system and the rapping system, which supply, for example, Jay go Inc., US (JRB series and Novamix), Paul O. Abbe Inc., US (series Rota-Cone, Rota-U, Rota Blade, Cylindrical Ribbon/Paddle, Plow and Sigma-blade), Forberg A/S, NO. (series Forberg II), Gemco Inc., US (series D/3 Double Cone, V-Shape, and Slant-Cone), LittlefordDay Inc., US (series Double Arm, Day Nauta and Daymax), Patterson-Kelly, Harsco Corp., US (series P-K Solids Processor®), Diosna, as stated above (series CCS and VAC), Romaco Zanchetta SpA, IT (in the Roto E D Roto and Roto P) and L. B. Bohle Maschinen und Verfahren GmbH GmbH, DE (series Granumator GMA Vagumator VMA). The above equipment is usually also provides drying the obtained granules.

Accordingly, it is preferable that the specified substance was a disaccharide, preferably lactose, more preferably lactose - α - monohydrate. The specified polysaccharide preferably is a cellulose, and more preferably microcrystalline cellulose.

In the method according to the present invention manufactured solid dosage form is typically suitable for oral administration a tablet. As an example of the equipment, which was carried out by a tabletting, is single rotary press with 45 press kits and a feeder with independent drive.

In a preferred embodiment of the method according to the present invention the specified stage of mixing and formation of the granulate is carried out in a fluidized bed dryer granulator.

Moreover, as indicated above, the composition of the pharmaceutical composition, the content of active substance, desloratadine, is from 3 to 15% and the number of anti-friction, dezintegriruetsja, binders (additives) is contained in an amount of from 1 to 10%. As non-limiting examples of these additives, widely used and well-known expert in the field of pharmaceutical �industry, you can specify magnesium stearate, povidone and sodium croscarmellose. The preferred amount of active ingredient and additives, therefore, can range from 4 to 25% by weight of the tablet, more preferably but not necessarily from 10 to 20%, but most preferably, but not necessarily their content in an amount of from 12 to 15%, but especially preferred is a content of active substance and additives in the amount of 13%.

The method is preferably carried out in such a way as to achieve maximum strength tablets at optimum pressure for a given composition and at the same time for maximum performance on the above press. Other quality characteristics and indicators should correspond specified in the global Fund XI, issue.2, pp. 154-160 for the specified dosage forms. Moreover, despite the valid GF abrasion resistance 97%, one of the objectives of the present invention is to achieve the strength of resistance in the range of 99.2-99,99% because, as a rule, already after abrasion of less than 99.5% is not visible to the naked eye gouges and defects of the material.

To achieve this result, the authors of the present invention were used various combinations of compositions, such as combinations of fillers. Examples and options for describing the present invention, more �for details shown in table 1 and table 2. Table 1 shows the test results of different variants of compositions. Table 2 shows the compositions for each option in table 1. All versions were produced in the same way described below.

Specialist in the field of manufacture of pharmaceutical preparations well-known terms, methods and ways of determination shown in table 1 qualitative characteristics of the obtained tablets and are fully within the limits of his skills.

Table 1.
Option # FillerThe ratio of a substance 1 substance 2 (part)The content of the filler in the mass of tablets (%)Capacity (PCs / h)Abrasion resistance (%)Strength tablets for compression (N)
The substance 1Substance 2
1LactoseMCC10:187200 00098,245/td>
2LactoseMCC8:187200 00099,555
3LactoseMCC2:18715000099,970
4LactoseCorn starch6:1879800096,635
5Calcium hydrophosphateMCC6:187120 00098,760
6Calcium hydrophosphateMCC8:187133 00098,355
7 LactoseMCC1:18710600099,880
8LactoseMCC6:187200 00099,855

As indicated above, it is preferable to obtain from said resulting mixture granules with an average granule size of at least 100 μm, preferably in the range from 100 microns to 300 microns.

In a preferred embodiment of the method, as specified disaccharide and polysaccharide are present during mixing. Then the mass ratio of said disaccharide and polysaccharide is usually from 8:1 to 2:1.

The method is preferably carried out in such a way that the total number of the specified excipient, diluent and carrier in amounts from 75 to 96, preferably from 80 to 90 percent by weight of the pharmaceutical composition.

In the most preferred embodiment uses desloratadine is mixed with the specified excipient, diluent and/or carrier in an amount which in the end provides materialeigenschaften in an amount of from 3 to 50 mg per unit dosage forms.

Thus, the Most appropriate composition and wonderfully randomly selected combination of substances which filler dosage forms, 8 variant is indicated in the table. The authors of the present invention, experimentally as a result of multiple combinations and qualitative research characteristics, the received dosage forms, unexpectedly failed to find the optimal ratio of components, method and production technology to produce the best quality product at maximum performance.

The most preferred, but not required, is the following content of components in wt. %:

Specific option is the most preferred formulations of the claimed composition are presented in table 4.

The following are examples of the manufacture of tablets, which used for the formulation, in accordance with the invention, namely the number of desloratadine from 3 to 15% and filler from 75 to 96%, and also shows the use of lactose and MCC with an average particle size of from 30 to 200.

Examples of the preparation of tablets.

In the examples 1-4:

- when pressing the kernels of the productivity of the press was 200-210 thousand tablets per hour, variation in weight of individual �of Ableton did not exceed ±5% of average weight;

- used brand of fillers, characterized by an average particle size:

lactose monohydrate 450M with an average particle size of about 30 μm, brand Pharmatose 450M, manufacturer Friesland Foods, the Netherlands,

lactose monohydrate SD with an average particle size of about 200 microns, brand Fast Flo, producer of "Foremost Dr.", USA,

ICC-105 with an average particle size of about 30 μm, brand VIVAPUR105, manufacturer JRS Pharma, Germany,

MKC-200 with an average particle size of about 200 microns, brand Comprecel M200D+, manufacturer MINGTAI", Taiwan.

Example 1

Desloratadine, lactose and MCC are mixed in a laboratory mixer cubic form, then sieved through a sieve with hole size of 0.63 mm and again placed in a mixer, add colloidal silicon dioxide and magnesium stearate. The mixture was sieved again through a sieve. Sifted the mixture is compressed using presentemente diameter of 10 mm round biconvex cylindrical shape. Get core tablets with a compression strength of 110-N and abrasion resistance of 99.4%, which is then covered with a film cover, by spraying an aqueous suspension of the core in a perforated rotating drum.

Example 2

Desloratadine, lactose, MCC, and croscarmellose sodium are mixed in a paddle mixer. A mixture of granular�Ute in a laboratory fluidized bed dryer granulator by spraying it through the nozzle of an aqueous solution of povidone 25. After the granulation product was dried in the same equipment to a residual moisture content of 2-3%, then add magnesium stearate and include fluidization for a few seconds. The resulting mixture is passed through a sieve of 0.63 mm and pressed her core tablets with a diameter of 6 mm round biconvex cylindrical shape. The strength of cores resistance 99.8%, the compression strength 95-100N.

Example 3

Desloratadine, lactose, MCC, povidone, croscarmellose sodium, colloidal silicon dioxide and sodium fumarate are mixed in a paddle mixer for 30 seconds. The mixture was passed through a conical mill with an installed grid with a hole diameter of about 2 mm Sieved the mixture is compressed into tablets capsulorraphy forms that have the strength compression of 80-100N and abrasion resistance of 99.5%..

Example 4

Desloratadine, lactose, MCC, and half of the magnesium stearate, are mixed in a paddle mixer and passed through the sealing rolls, the compacted material is then milled in a conical mill, and mixed in a mixer with the rest of the magnesium stearate. The mixture is compressed tablets with a diameter of 9 mm round biconvex cylindrical shape. The strength of cores resistance 99.8%, the compression strength 70-N.

1. Le�artena form, contains desloratadine as active ingredient in an amount of from 3 to 15%, processing AIDS and pharmaceutically acceptable filler, where the filler is a mixture of the disaccharide lactose and polysaccharide cellulose microcrystalline, taken in the ratio from 2:1 to 8:1, for the manufacture of dosage forms weighted desloratadine, lactose monohydrate, microcrystalline cellulose are mixed in a mixer, the resulting mixture granulated, calibrate, dusted and tableted, and use lactose and microcrystalline cellulose with an average particle size of from 30 to 200 microns.

2. Pharmaceutical form according to claim 1, where the specified ratio is in the range from 4:1 to 7:1.

3. Pharmaceutical form according to claim 1, where the specified ratio is in the range from 5:1 to 6:1.

4. Pharmaceutical form according to claim 1, where the specified ratio is 6:1.

5. Pharmaceutical form according to claim 1, where the total amount of filler is 75-96% by weight of the tablet.

6. Pharmaceutical form according to claim 1, where the composition of these technological additives contains croscarmellose sodium.

7. Pharmaceutical form according to claim 1, where the composition of these technological additives contains magnesium stearate.

8. Pharmaceutical form according to claim 1, where the composition of these technological additives contains povidone.

9. Drug�idents form according to any one of claims.6-8, where these technological additives contained in an amount of from 1 to 10%.



 

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1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the pharmaceutical industry, namely to a formulation of a cough medical composition. The formulation of the cough medical composition contains an active substance presented by thermopsis herb powder or a dry extract of thermopsis and sodium hydrocarbonate, as well as an excipient, a granulating agent and a lubricant taken in certain relations (versions).

EFFECT: composition of the cough medical composition possesses improved pharmaceutical (appearance, taste) and technological characteristics (hardness, disintegration).

11 cl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a storage-stable pharmaceutical composition and a pharmaceutical formulation containing at least one active pharmaceutical ingredient presenting a nitrocatechol derivative, 2,5-dichlor-3-(5-(3,4-dihydroxy-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide, at least one excipients and at least one binding agent, wherein at least one excipient is other than a phosphate derivative, wherein at least one binding ingredient is other than a polyvinylpyrrolidone compound, and wherein the above active pharmaceutical ingredient is present in the granulated form.

EFFECT: compositions and/or formulations according to the invention are stable for a long period of time and show a high stability if stored in the high temperature and moisture environment.

26 cl, 8 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: amlodipine base or its pharmaceutically acceptable salt, preferentially amlodipine besylate, bisoprolol fumarate, a disintegrating agent, a wetting agent, and if necessary additional excipients are homogenised; an antiadhesion agent is added, and the homogenisation procedure is continued; the homogenate is then tabletted by direct compression, or solid gelatine capsule is filled in; the prepared tablets or capsules are packed in moisture-proof protective packaging. The prepared tablets or capsules contain less than 0.5 wt % of active ingredients of compounds of formula

.

EFFECT: what is described is a method for preparing the stable solid pack dosage form containing the amlodipine base or its pharmaceutically acceptable salt and bisoprolol fumarate.

3 cl, 6 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to the pharmaceutical industry and provides a multilayered tablet, containing an effervescent layer, containing hydrochlorothiazide or amlodipine or its salt as an active ingredient, carbonate salt and organic acid, and a telmisartan-containing layer.

EFFECT: obtaining the multilayered tablet, containing the effervescent layer.

1 dwg, 9 tbl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention concerns a hot-melt extruded pharmaceutical dosage form with controlled-release pharmaceutically active ingredient (A) enclosed in a matrix containing polymer (C). A core of the pharmaceutical dosage form is morphologically oriented according to the holt-melt extrusion, which is substantially orthogonal to a long direction of the dosage form; and/or a release per a unit area of the pharmacologically active ingredient (A) through a front side and an opposite back side is faster than that through an annular ring.

EFFECT: dosage form shows min breaking strength 300 H; it has an oblong shape with the long direction and the cross direction orthogonal to the long one, with the front side opposite to the back side, and the annular rim between the above front and back sides.

11 cl, 20 tbl, 3 ex, 13 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to medicine. What is described is a pharmaceutical composition containing licarbazepine acetate, preferentially eslicarbazepine acetate, in a combination with acceptable excipients, particularly a binding agent and a disintegrating agent. What is also described is a method for wet granulation for preparing the pharmaceutical composition.

EFFECT: composition is compacted as a tablet, which has reduced size and volume density.

79 cl, 10 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a method for producing a tablet by (i) compressing a powder mixture in a mould plate of one device for producing a tabletted form with the powder mixture comprising a pharmaceutically active substance and a fusible binding agent, and (ii) exposing the above tabletted form to radio-frequency radiation generated by the above device over a period of time adequate to soften or melt the binding agent inside the above tabletted form to produce a tablet. Oral absorption of the produced tablet placed on the tongue takes less than approximately 30 s.

EFFECT: more effective method for producing the tablet by (i) compression.

18 cl, 14 dwg, 7 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: invention provides a composition having antioxidant properties in the form of a tablet, comprising an active agent based on nicotinamide adenine dinucleotide in reduced form (NADH) and inert filling agents, characterised by that the active ingredient is a complex which is a mixture of 10 wt % NADH with 63 wt % vegetable fats, 17 wt % beeswax and 10 wt % chlorophyll, and the inert filling agents are in the form of microcrystalline cellulose, Macrogol 6000, intense sweetener and a food flavourant.

EFFECT: invention provides a new tablet form of NADH.

1 ex

FIELD: chemistry.

SUBSTANCE: as active component pharmaceutical composition contains dihydrochloride of 9-(2-morpholine ethyl)-2-(4-fluorophenyl)imidazo[1,2-α]benzimidasol, and as additional substances - fillers, binding, sliding and film coatings, in quantities, given in the invention formula. Composition can be made in form of solid medication form, mainly in form of tablets and capsules.

EFFECT: obtained solid medication forms satisfy the requirements of the State Pharmacopoeia.

7 cl, 2 dwg, 3 tbl, 14 ex

FIELD: medicine.

SUBSTANCE: invention refers to a pharmaceutical composition with anti-ischemic and antioxidant activity in the form of tablets or capsules, and a method for preparing it. The composition contains 4-((3-oxo-3-ethoxypropanoyl)amino)benzoic acid in an amount of 40 to 80 wt %, an amino-containing compound and pharmaceutically acceptable excipients. The amino-containing compound is specified in a group of trometamol, methyl glucamine and L-lysine; 1 mole of 4-((3-oxo-3-ethoxypropanoyl)amino)benzoic acid is accounted for 0.05 to 0.25 mole of the above amino-containing compound. The composition also contains lactose, microcrystalline cellulose, calcium stearate and other pharmaceutically acceptable excipients. According to the method for preparing the composition, taking 4-((3-oxo-3-ethoxypropanoyl)amino)benzoic acid and amino-containing compound in molar ratio 1:0.05 to 1:0.25, pre-mixing, moisturising with a aqueous or alcohol solution of a binding agent, adding pharmaceutically acceptable excipients in such an amount to provide the content of 4-((3-oxo-3-ethoxypropanoyl)amino)benzoic acid from 40 to 80 wt %, granulating the mixture, drying and producing tablets or capsules according to the known technique.

EFFECT: implementing the above application.

6 cl, 7 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: invention refers to a pharmaceutical composition containing a compound presented by formula (I) , wherein R1 represents a hydrogen atom, C1-6 alkyl group or C3-8 cycloalkyl group; while R2 represents a hydrogen atom or a methoxyl group, or its pharmaceutically acceptable salt, or solvate; and alkaline earth carbonate, wherein the content of the compound presented by formula (I), or its salt or solvate makes 0.25 to 50 wt %, and the content of alkaline earth carbonate makes 1 to 60 wt % in relation to total weight of the composition, respectively.

EFFECT: composition exhibits excellent solubility; it is storage-stable or even long-term storage-stable, and applicable as a preventive or therapeutic agent for treating a tumour.

10 cl, 7 dwg, 10 tbl, 19 ex

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