Pharmaceutical composition for treating arterial hypertension and congestive cardiac failure and method for preparing it

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, more specifically to an agent to be used for treating arterial hypertension and congestive cardiac failure. A pharmaceutical composition contains ramipril, a combination of sodium bicarbonate and arginine as a stabiliser, lactose monohydrate, microcrystalline cellulose, hypromellose, sodium croscarmellose, glidant and a lubricant and optionally a dying agent. A method for preparing the pharmaceutical composition involves moisturising of a mixture of ramipril, lactose monohydrate, microcrystalline cellulose, sodium bicarbonate, and optionally the dying agent in a solution of hypromellose and arginine, granulation, drying, dry granulation, addition of sodium croscarmellose, glidant and the lubricant, and tableting of the prepared mixture. The pharmaceutical composition in the form of a solid dosage form is characterised by decreased formation of all impurities, including ramiprilate and diketopiperazine ramipril, fast release of the active substance, high strength and storage stability of the quality characteristics guaranteed within more than 2 years of shelf life.

EFFECT: preparing the agent for treating arterial hypertension and congestive cardiac failure.

11 cl, 2 tbl, 12 ex

 

The invention relates to medicine, specifically to a tool that can be used for the treatment of hypertension and congestive heart failure.

Ramipril, 1-ethyl ester of (2S,3aS,6aS)-1[(S)-N-[(S)-1-carboxy-3-phenylpropyl]alanyl]octahydrocyclopenta[b]pyrrole-2-carboxylic acid, an inhibitor of angiotensin-converting enzyme (ACE). Ramipril is used to treat hypertension, heart failure, stroke, myocardial infarction, diabetes and diseases of the cardiovascular system. Ramipril and its acidic form, ramiprilat, described in the patent EP 0097022 B1.

Obtaining a stable pharmaceutical compositions ramipril difficult, since ramipril is prone to certain types of decomposition. It can undergo cyclization through an internal nucleophilic attack, hydrolysis and oxidation, to form substituted diketopiperazine, ramipril decollato and products deeper destruction.

In the application US 2003/0215526 described pharmaceutical compositions of the ACE inhibitor containing a therapeutically effective amount of ACE inhibitor-sensitive decomposition, or its salt; carbonate of alkali or alkaline-earth metal in excess of stoichiometric with respect to the ACE inhibitor or its salt, and a pharmaceutically acceptable carrier.

In Patan is e ER 0280999 B1 described composition, containing ACE inhibitor, a carbonate of alkali or alkaline earth metal and a saccharide in which the ACE inhibitor stabilized against decomposition due to the presence of the other mentioned ingredients. In the description of the patent suitable saccharides called lactose and mannitol. Also in the description mentioned modified starch as dezintegriruetsja agent. However, the known compounds with ramipril as the active substance is not sufficiently stabilized against degradation.

In the patent EP 0317878 B1 describes a stable compressed pharmaceutical composition comprising a compound formula (under which the subject ramipril), where to stabilize before pressing the connection of this formula a) cover physiologically acceptable polymer protective coating, or (b) is mixed with a physiologically acceptable buffer which maintains the pH of the pharmaceutical composition in the presence of moisture in the range from slightly acidic to slightly alkaline values, where sodium bicarbonate is excluded from the number of possible buffers, or C) is mixed with a physiologically acceptable buffer, ensuring that the pH of the pharmaceutical composition in the presence of moisture in the range from slightly acidic to slightly alkaline values and cover the physiologically acceptable polymer protective coating, DG is, in the case of stabilization Pb) carbonate of alkali or alkaline-earth metal in the composition do not add sugar. The disadvantages of this composition should include the complexity of the technology.

In Russian patent application RU 2007120821 (WO 2006/052968) described pharmaceutical composition, which contains ramipril covered component mixture, where the component of the mixture is selected from glyceraldehyde, glycerylmonostearate, stearyl alcohol, simple ester macrogalleria, palmitostearate, ethylene glycol, polyethylene glycol, stearic acid, cetyl alcohol, lauric alcohol, amylopectin, poloxamer or combinations thereof, preferably glycerinated. However, this composition has problems with the release of the active substance.

In Russian patent application RU 2006133453 (WO 2005079762) proposed a multilayer tablet comprising a first layer containing telmisartan in soluble matrix tablets, and a second layer containing ramipril in disintegrating matrix tablet. In order to stabilize telmisartan dissolving the matrix may contain an alkaline agent chosen from the group comprising hydroxides of alkali metals, alkaline amino acids, for example arginine, and meglumin, preferably sodium hydroxide. The use of arginine to stabilize ramipril is not specified.

In the Eurasian PA is ente EA 11862 described pharmaceutical composition ramipril, including as a stabilizing substance is a combination of sodium bicarbonate and dihydrate calcium sulphate (prototype). Known composition as auxiliary substances may include - disintegrity agent, binding agent, such as starch, and a moving substance, such as sodium fumarate. Known composition is particularly stable against the formation of diketopiperazine, however, apply the stabilizer is not effective enough in respect to the education of other degradation products, such as ramipril of decollate.

The objective of this invention is to provide a drug for the treatment of hypertension and congestive heart failure on the basis of ramipril in the form of solid dosage forms having a high therapeutic activity, stable during storage, characterized by high values of the rate of release of the active substance and having a shelf life of over 2 years.

The problem is solved by a pharmaceutical composition comprising ramipril, combined stabilizing substance on the basis of sodium bicarbonate, filler, binder, disintegrant, moving substance, characterized in that it contains as a stabilizing substance is a combination of sodium bicarbonate and arginine.

The composition could critique the sustained fashion to contain the dye, preferably iron oxide yellow and iron oxide red. As filler can be used lactose monohydrate, microcrystalline cellulose or a combination thereof, preferably a combination of lactose monohydrate and microcrystalline cellulose in a ratio of 6 to 10 parts of lactose monohydrate to 1 part of microcrystalline cellulose. As the binder can be applied hypromellose or starch, preferably hypromellose. As disintegrant used sodium carboxymethyl starch, crosspovidone or croscarmellose sodium, preferably croscarmellose sodium. Moving substance includes glidant and lubricant. As glidant used colloidal silicon dioxide, silica methylated or their combination, it is preferable combination of colloidal silicon dioxide and silicon dioxide methylated in the ratio of 1:1. As the lubricant is preferably used sodium stearyl fumarate.

The active ingredient in the proposed composition is ramipril. Ramipril is an ACE inhibitor, is a prodrug, which the body produces an active metabolite ramiprilat, has a vasodilator effect. Used in hypertension, chronic heart failure.

In the preferred embodiment, and is gaining the composition contains ramipril and combined stabilizer in the following ratio, parts by weight of

Ramipril - 1,0

Sodium bicarbonate - 0,005-1,0

Arginine - 0,002-1,0

Introduction to the composition of arginine in combination with sodium bicarbonate significantly reduced the formation of such impurities as ramipril dikelola and other impurities, hereinafter referred to in text as unidentifiable impurities, while maintaining good inhibition of the formation of diketopiperazine ramipril.

Studies have shown high stability of the claimed composition. The stability of the drug was studied during storage (table 1). The claimed composition showed excellent stability on education impurities decollate (impurity E) and other impurities specified as the sum of unidentifiable impurities, while maintaining good stability by the formation of impurities of diketopiperazine, the content of the latter was a year of storage of 0.9-1.0% and after 2 years of 1.8-2.0%. The number of impurities are relative to the initial content ramipril

Table 1
Impurities, %Examples (shelf life-1 year/2 years)
15712
The mixture of decollate0,02/0,13/0,150,02/0,10/0,110,02/0,12/0,150,05/0,08/0,11
The amount of unidentifiable impurities0,07/0,18/0,200,07/0,15/0,170,05/0,15/0,180,08/0,11/0,15

The resulting tablets have a sufficient strength, high rate of release of the active substance, stable quality and shelf life of more than 2 years.

The preferred ratio of ingredients of the inventive compositions is, parts by weight:

Ramipril - 1,0

Sodium bicarbonate - 0,01-1,0

Arginine - 0,005-1,0

Filler - 1,4-745,6

Binder is 0.01 to 3.2

Disintegrant - 0,03-12,8

Glidant - 0,03-12,8

Lubricant - 0,02-6,4

Dye 0,001-0,06

A distinctive feature of the method of obtaining the claimed composition, which comprises moistening a mixture of ramipril, filler, sodium hydrogen carbonate and, optionally, a dye solution of a binder and arginine, granulation, drying, dry granulation, adding disintegrant, glidant and lube and tableting ready mix is the introduction of arginine in the form of a solution together with a binder.

A new pharmaceutical composition is performed, preferably, in the form of what tabletki.

Examples of carrying out the invention is presented in Table 2. A typical example (example 1). If the composition tabletas mass of dye to achieve a uniform coloring of the tablets separately prepare a mixture of parts of filler and dye. For this pre-sifted (2 times) powder iron oxide yellow/iron oxide red mixed with a small amount of sifted powder filler and the resulting mixture was manually thrice sifted through a sieve with mesh size from 114 microns.

Pre-sifted powder substance ramipril, filler, sodium bicarbonate and pre-mixed part of the filler with the dye mix until smooth, granularit solution moisturizer containing a binder and arginine, dry and grind the resulting granulate. To ground the granulate add disintegrant, glidant and lubricant and ready weight tabletirujut. Get tablets with an average weight 0,100 g (dosage of 1.25 mg), 0,200 g (dosage 2.5 mg), 0,13 g (dosage 5 mg) and 0.26 g (dosage 10 mg) and strength 65÷85 N (dosage of 1.25 mg), 90÷110 N (dosage 2.5 mg), 80÷95 N (dosage 5 mg) and 95÷105 N (dosage 10 mg).

The obtained tablets satisfy regulatory requirements in the pharmaceutical agent. Dissolution, % release ramipril on Wednesday dissolution in 0.1 N acid solution PI is estevadeordal - after 30 minutes (HPLC) - 100 (no less than 75 regulations), the content of ramipril in one tablet (HPLC) - 1.25 mg (dosage of 1.25 mg, 2.5 mg (dosage 2.5 mg), 5.0 mg (dosage 5 mg) and 10.0 mg (dosage 10 mg). The resulting tablets have a shelf life of over 2 years.

1. Pharmaceutical composition for treatment of cardiovascular diseases in the form of a solid dosage form that contains the active ingredient ramipril in therapeutically effective amount, the combination of sodium bicarbonate and arginine as a stabilizer, lactose monohydrate, microcrystalline cellulose, hypromellose, croscarmellose sodium, glidant and lubricant.

2. The pharmaceutical composition according to claim 1, characterized in that it additionally contains a dye.

3. The pharmaceutical composition according to claim 2, characterized in that it contains as a colorant iron oxide yellow and iron oxide red.

4. The pharmaceutical composition according to claim 2, characterized in that it contains ramipril, sodium bicarbonate and arginine in the following ratio, parts by weight:

Ramipril1
Sodium bicarbonateof 0.005 to 1.0
Arginine 0,002-1,0

5. The pharmaceutical composition according to claim 4, characterized in that it contains as glidant combination of colloidal silicon dioxide and silicon dioxide methylated and as lubricant is sodium stearyl fumarate.

6. The pharmaceutical composition according to claim 5, characterized in that it is made in tablet form.

7. The pharmaceutical composition according to claim 6, characterized in that it contains one tablet of ramipril in the amount of 1.25 mg

8. The pharmaceutical composition according to claim 6, characterized in that it contains one tablet of ramipril in the amount of 2.5 mg

9. The pharmaceutical composition according to claim 6, characterized in that it contains one tablet of ramipril 5 mg

10. The pharmaceutical composition according to claim 6, characterized in that it contains one tablet of ramipril in the amount of 10 mg.

11. A method of obtaining a pharmaceutical composition according to claims 1 to 10, which comprises moistening a mixture of ramipril, lactose monohydrate, microcrystalline cellulose, sodium hydrogen carbonate and, optionally, a dye solution hypromellose and arginine, granulation, drying, dry granulation, adding croscarmellose sodium, glidant and lube and tableting mixture.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula (I) possessing a property of DGAT inhibitor, its N-oxides, its pharmaceutically acceptable salts and solvates, as well as to a based pharmaceutical composition and their application. In general formula (I) , A represents CH or N; a dash line represents an optional bond provided A represents a carbon atom; X represents -O-C(=O)-; -NRx-C(=O)-; -Z-C(=O)-; -Z-NRx-C(=O)-; -NRX-C(=S)-; Z represents C1-6alkandiyl; Rx represents hydrogen; Y represents -C(=O)-NRx- or -NRx-C(=O)-; R1 represents aryl1 or Het1; R2 represents C3-6cycloalkyl, phenyl, 2,3-dihydro-1,4-benzodioxynyl, or a 6-member aromatic heterocycle containing 1 or 2 N atoms wherein said phenyl or the 6-member aromatic heterocycle containing 1 or 2 N atoms may be optionally substituted by one, two, three or four substitutes with each substitute independently specified in a group consisting of halogen; C1-6alkyl, C1-6alkyloxy, C1-6alkylthio; C1-6alkyloxycarbonyl, nitro; mono- or di(C1-4alkyl)amino; R4R3N-C1-6alkyl; Het-C(=O)-C1-4alkyl; R3 represents C1-4alkyl; R4 represents C1.4alkyl; R5 represents hydrogen; C1-4alkyl; C1-4alkylcarbonyl; R6 represents hydrogen or C1-4alkyl; or R5 and R6 may be taken together with a nitrogen atom whereto bound to form a saturated monocyclic 5, 6 or 7-member heterocycle which may additionally contain one or more heteroatoms each of which independently specified in O, S, S(=O)P or N; and such heterocycle may be optionally substituted by C1-4alkyl; R' represents hydrogen or halogen; aryl represents phenyl or phenyl substituted by halogen, C1-6alkyl, polyhalogen C1-6alkyl; C1-6alkylxoycarbonyl; aryl represents phenyl or fluorenyl; each of said phenyl or fluorenyl may be optionally substited by one or two substitutes with each substitute independently specified in a group involving oxo; carboxyl; halogen; C1-6alkyl optionally substituted by carboxyl or C1-4alkyloxycarbonyl; C1-6alkyloxy; C1-6alkyloxycarbonyl; amino; aryl; Het; Het represents a monocyclic nonaromatic or aromatic heterocycle containing at least one heteroatom each independently specified in O, S, S(=O)p or N; or a bicyclic nonaromatic or aromatic heterocycle containing at least one heteroatom each independently specified in N; said monocyclic heterocycle or said bicyclic heterocycle may be optionally substituted by at least one or two substitutes with each substitute independently specified in a group containing oxo; or C1-6alkyl; Het1 represetns a monocyclic nonaromatic or aromatic heterocycle containing at least one heteroatom each independently specified in S or N; said monocyclic heterocycle may be optionally substituted by one substitute, particularly by one or two substitutes with each substitute independently specified in a group consisting of hydroxyl, oxo, C1-6alkyl, C1-6alkyloxycarbonyl, aryl; Het; p has the value of 2.

EFFECT: there are presented new piperidine/piperazine derivatives.

17 cl, 10 tbl, 146 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to chemical-pharmaceutical industry, more specifically to (1-hydroxy-4,5-dimethyl-1H-imidazol-2-yl)(phenyl)methanonoxime of formula (1)

EFFECT: what is prepared is a new compound possessing antiarrhythmic activity and low toxicity.

2 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: endothelial dysfunction is induced in experimental Wistar male rats for 28 days by daily intraperitoneal introduction of N-nitro-L-arginine methyl ester (L-NAME) 12.5 mg/kg a day. An agent for dysfunction correction is a mixture of solutions of homoeopathic dilutions of tumour necrosis factor-alpha (TNF-α) antibodies - C12, C30, C200. This mixture is introduced at the same time for 28 day intragastrically 2 times a day in a dose of 4.5 ml/kg.

EFFECT: effective endothelial dysfunction correction.

1 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to compounds of formula (I) or pharmaceutically acceptable salts of such a compound, where R1 is an unsubstituted phenyl; R2 is -CO-R21; R21 is C1-5alkyl; m equals 3; p equals 2 or 3; and R3 is hydrogen. The invention also relates to specific compounds of formula ,

a pharmaceutical composition based on the compound of formula (I) and use of the compound of formula (I).

EFFECT: novel compounds which are useful as T/L channel blockers are obtained.

6 cl, 1 tbl, 8 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmacology in cardiology, particularly to a herbal tea for treating the adolescents suffering stable arterial hypertension. The herbal tea for treating the adolescents suffering stable arterial hypertension containing dried grinded herbal raw material: creeping thyme herb, Baical woundwort herb, rose hips, Siberian patrinia roots in certain proportions.

EFFECT: herbal tea is effective for treating the adolescents suffering stable arterial hypertension.

2 cl

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly clinical pharmacology and cardiology, and may be used for achieving target arterial pressure in the patients suffering degree 1-2 arterial hypertension (AH). A start antihypertensive preparation is individually selected by taking into account systolic arterial blood pressure (SABP) variations in passive orthostatic test. The measurements are taken in an initial horizontal position on the first, fifth, tenth and fifteenth minutes of the test. A response index (RI) is calculated by formula: If the RI is less than zero, a monotherapy with an angiotensin converting enzyme inhibitor is required. If the RI is equal to zero or more, a combined therapy with the angiotensin converting enzyme inhibitor Zofenopril and the beta-adrenoreceptor blocking agent Nebivolol is required.

EFFECT: method provides a differentiated approach to selection of the start therapy in this group of patients for achieving target pressure.

2 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine and concerns methods of treating acute cerebrovascular disease. A method of treating acute ischemic and hemorrhagic cerebrovascular disease consists in administering a pharmaceutical composition containing a protein-polypeptide complex taken as a biologically active substance and prepared of fast-frozen embryo brain of hoofed farm animals of a gestation term from the middle of the first one-third to the middle of the last one-third of pregnancy, in the amount of 0.05-0.8 mg/day subcutaneously, intramuscularly, intravenously, intranasally and intrathecally. Said protein-polypeptide complex contains negative weak acid neutral proteins and polypeptides referring to growth/differentiation factors, signal molecules, intercellular adhesion molecule, of molecular weights 5 to 200 kD with min. 80% of total weight of proteins having molecular weight 10 to 120 kDa, and characterised nu a peak at UV wave length 274-284 nm and bands at the pi values of 4.2 to 8.4 at isoelectric focusing in 5% polyacrylamide gel.

EFFECT: protein-peptide complex is safe and tolerable when in use; it is effective in treating the patients with acute cerebrovascular disease that ensures clinically significant effect of survivability, dynamics and recovery length of the lost functions in the patients when using the method.

4 cl, 9 tbl, 23 ex

FIELD: medicine.

SUBSTANCE: endothelial dysfunction is induced in experimental Wistar male rats for 28 days by daily intraperitoneal introduction of N-nitro-L-arginine methyl ester 12.5 mg/kg a day. An agent for dysfunction correction is a mixture of solutions of homoeopathic dilutions of interleukin-6 antibodies - C12, C30, C200; it is introduced at the same time for 28 day intragastrically 2 times a day in a dose of 4.5 ml/kg.

EFFECT: method provides effective endothelial dysfunction correction.

1 tbl

FIELD: medicine.

SUBSTANCE: endothelial dysfunction is induced in experimental Wistar male rats for 28 days by daily intraperitoneal introduction of N-nitro-L-arginine methyl ester (L-NAME) 12.5 mg/kg a day. The mixed solutions of homoeopathic dilutions of polyclonal rabbit human endothelial nitrogen oxide synthase antibodies C12, C30, C200 are used as an agent for dysfunction correction. This mixture is introduced at the same time for 28 day intragastrically 2 times a day in a dose of 4.5 ml/kg.

EFFECT: method provides effective correction of said dysfunction with eNOS increase.

1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: what is presented is using amide N-succinyl-L-glutamide-L-lysine (GC-1) representing a dipeptide agonist of nerve growth factor as an antiarrhythmic and antifibrillatory agent for preventing sudden cardiac death. It is shown that the agonist of nerve growth factor - the GC-1 compound (1 mg/kg intravenously) on a model of electrical ventricular fibrillation possess antiarrhythmic (antifibrillatory) action being as good as reference antiarrhythmic drug preparations of Vaughan Williams class I and III.

EFFECT: obtained data give ground for presenting using the GC-1 dipeptide as an antiarrhythmic (antifibrillatory) drug preparation which may be used in clinical practise for preventing sudden coronary death.

1 dwg, 2 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to medicine, namely pharmacy and may be used for creating an oral solid dosage form. The dosage form contains a pharmaceutically acceptable salt of an alkaline-earth metal of 5-methyk-(6S)-tetrahydrofolic acid and granules containing progestogen, oestrogen and microcrystalline cellulose. What is also presented is a pharmaceutical kit for females for providing the concentrations or treating the diseases, conditions or symptoms associated with endogenous oestrogen deficiency.

EFFECT: group of inventions provides the good storage stability of tetrahydrofolic acid, and at the same time provides rapid and reliable release of oestrogen and progestogen being parts of the composition.

13 cl, 3 dwg, 4 tbl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of medicine and deals with combined pharmaceutical composition, which possesses anti-tuberculosis action. Composition is made in form of solid drug form, which contains combination of levofloxacin, protionamide, pyrazinamide, ethambutol hydrochloride and pyridoxine hydrochloride ad active ingredient, and pharmaceutically acceptable auxiliary substances.

EFFECT: composition is characterised by high therapeutic activity.

10 cl, 2 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to tablet, which is decomposed in mouth, containing D-mannite, active ingredient, disintegrating preparation, selected from crospovidone and carmellose, lubricant, selected from sodium stearylfumarate and sucrose esters of fatty acids, binding agent and starch. D-mannite has average size of particles larger than 30 mcm and specific surface larger than 0.40 m2/g.

EFFECT: claimed tablet has time of decomposition in oral cavity within 30 seconds, excellent sensation in oral cavity and sufficient strength, as a result of which tablet is not decomposed in the process of distribution.

28 cl, 1 dwg, 12 tbl, 51 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to chemical-pharmaceutical industry and represents a pharmaceutical composition containing: {1S-[1α,2α,3β(1S*,2R*),5β]}-3-(7-{[2-(3;4-difluorophenyl)cyclopropyl]amino)-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol; an excipient representing mixed mannitol and dibasic calcium phosphate dihydrate; a binding agent representing hydroxypropyl cellulose; a disintegrant representing sodium starch glycolate; and one or more lubricating agents.

EFFECT: invention provides preparing the composition of the active compound possessing high stability and high bioavailability of the active agent.

12 cl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to chemical-pharmaceutical industry and represents a drug preparation containing 97.0-59.5 wt % of naltrexone base, 0.5-3.0 wt % of corticosteroid specified in triamcinolone, betamethasone or dexamethasone, 2.0-37.0 wt % of a nitrogen-containing polymer composition and 0.2-0.5 wt % of stearic acid or magnesium stearate. The nitrogen-containing polymer composition contains N-vinylpyrrolidone and 2-methyl-5-vinylpyridine copolymer or a salt of branched oligomers hexamethylene diamine and guanidine, and polyvinylpyrrolidone. The drug preparation may be used in addictology for treating the alcohol- or opioid-dependent patients.

EFFECT: invention provides prolonged and uniform naltrexone release with a lower probability of the implant rejection caused by an inflammatory response.

2 cl, 3 ex, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutics and medicine, namely a stable pharmaceutical composition of a water-soluble salt of vinorelbine. The composition contains approximately 56 wt % of a diluent, approximately 2.5 wt % of a binding agent, approximately 5 wt % of a disintegrant, approximately 0.25 wt % of a flow agent and approximately 0.5 wt % of a lubrication agent. The water-soluble salt of vinorelbine is preferentially vinorelbine ditartrate.

EFFECT: pharmaceutical composition is preferentially presented in the form of a gelatine capsule or a tablet.

5 cl, 6 ex, 12 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to pharmacology and medicine. The group of inventions involves pharmaceutical compositions containing 5-azacytidine for the oral introduction wherein the compositions release a cytidine analogue substantially in stomach, a method of treating an individual suffering a disease associated with abnormal cell proliferation which involves the oral introduction of the pharmaceutical composition into the individual, using 5-azacytidine for preparing the pharmaceutical composition for treating the disease associated with abnormal cell proliferation.

EFFECT: invention provides higher clinical effectiveness.

9 tbl, 9 ex, 23 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: pharmaceutical composition applicable for oral administration contains an S1P receptor agonist and mannitol with the composition representing a solid dosage form. Mannitol has a particle specific surface area 1 to 7 m2/g, and the S1P receptor agonist is specified from 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol (FTY720), its pharmaceutically acceptable salt and FTY720-phosphate.

EFFECT: compositions under the invention are characterised by a high level of distribution uniformity of said S1P receptor agonist, and applicable for oral administration in the solid dosage form, eg in the form of a tablet or a capsule.

14 cl, 39 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: method for preparing a pharmaceutical composition consists in mixing an S1P receptor agonist - 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol or its pharmaceutically acceptable salt with sugar alcohols; the mixture is milled and/or granulated, and then mixed with an oil agent. The method under invention is implemented on high-speed automated equipment and enables producing the compositions with high-level distribution uniformity of 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol or its pharmaceutically acceptable salt in the composition applicable for oral administration of said S1P receptor agonist.

EFFECT: preparing the pharmaceutically acceptable salt in the composition applicable for oral administration of said S1P receptor agonist.

15 cl, 39 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a pharmaceutical composition for treating and/or preventing depressions. The pharmaceutical composition contains an active substance presented by a selective serotonin reuptake inhibitor (SSRI) specified in a group of fluoxetine, paroxetine, citalopram, escitalopram, sertraline, fluvoxamine differing by the fact that as an active substance, it additionally contains N-acetyl-5-methoxytryptamine (melatonin) in the following proportions, mg: selective serotonin reuptake inhibitor (SSRI) - 10-30 mg, melatonin - 3-8 mg. The pharmaceutical composition may be presented by a solid dosage form - a tablet, a film-coated tablet, a capsule, by a soft dosage form - a rectal suppository.

EFFECT: pharmaceutical composition provides treating depressions and has a number of additional therapeutic properties: easing falling asleep and relieving sleeping disorders, recovering circadian rhythm and seasonal rhythm with reducing a risk of side effects of SSRI.

3 cl, 14 tbl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: coated pharmaceutical product for nicotine delivery into an individual in any form contains at least one core, nicotine in any form and/or a nicotine-imitating agent, at least one coating layer, and optionally one or more additions wherein at least said coating layer contains a buffer agent containing at least one amino acid. Amino acid is specified in a group consisting of asparagine, glutamic acid, glutamine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, serine, threonine, valine, cysteic acid, N-glycylglycine and ornithine. There are also provided a method for nicotine delivery in any form, a method for reduction of craving to smoke or use tobacco, as well as a method for preparing said coated product and applying it for ensuring fast oral nicotine absorption.

EFFECT: invention provides fast oral nicotine absorption; pharmaceutical product under the invention is characterised by the satisfactory organoleptic properties.

49 cl, 3 tbl, 6 ex

Up!