Pharmaceutical composition with anti-ischemic and antioxidant activity and method for preparing it

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

 

Present group of inventions refers to medicine and pharmaceutical industry, namely to oral compositions containing chemical compounds with anti-ischemic and/or antioxidant properties, and the way they are received.

Known substances from the number of derivatives of malonic acid, which have kardiostimuliruyuschy properties [see, for example, and.with. 1780293 THE USSR, MKI SS 233/54, AK 31/16]. The possibility and method of producing compositions that meet the requirements of the GF, not checked.

Synthesized in SPFA connection - 4-((3-oxo-3-ethoxypropanol)amino)benzoic acid (hereinafter APABC) is known and belongs to a number of derivatives of malonic acid [patent Application No. 2012105369 of the Russian Federation, patent 2167852 of the Russian Federation].

However, pharmacological properties and toxicity of this compound remained unexplored, and it was not possible to consider it as a possible substance medicines.

Studies have shown that this compound, both individually and as part of a pharmaceutical composition manifests in the experiment, anti-ischemic and antioxidant activity (Examples 4-6 in the description text).

Anti-ischemic effect APABC and pharmaceutical compositions based on it is manifested in the form of the positive effects on systolic dimensions of the left atrium and W�Lidochka, the absence of myocardial hypertrophy, improve blood flow in the pulmonary artery. The infusion of APABC were detected phenomena such as aneurysm, synergy, akinesia, there was no thrombus formation.

The infusion of APABC observed acceleration of repair processes of the myocardium and reducing areas of necrosis, increased uptime, improved contractile activity of the myocardium.

The values of antioxidant activity of the tested substance APABC and farbkomposition on its basis can be attributed to this compound to substances with a moderate antioxidant activity.

A study of acute toxicity of intraperitoneal and oral administration found that the tested pharmaceutical substance can be classified as low-toxic and non-toxic substances.

It is known that the oral formulations of drugs include, besides the active substance, the range is widely used in pharmaceutical technology excipients: sugar, starch, MCC, cellulose derivatives, stearates, carbonates and bicarbonates of metals, various polymers, etc., which provide the required technological properties of granules and tablets: strength, friability, disintegration, dissolution, etc. [see, for example, Belousov V. A. influence of the quality of the granulate for process steam�configure tableting materials (Review) / V. A. Belousov // Chem.-Pharm. log. 1981. No. 12. P. 76-80; Voskoboynikov I. V. Modern excipients in the manufacture of tablets. The use of high-molecular compounds for improved dosage forms and process optimization / V. I. Voskoboynikov [et al.] / / Chem.-Pharm. log. 2005. V. 39. No. 1. P. 22-28].

Known methods for the preparation of tablets and pellets for capsules that include the processes of mixing, wetting and granulating, drying, dry granulation (calibration), dusting, pressing [See, for example: Industrial technology of drugs / Ed. Professor V. I. Chueshov. Kharkiv: NUPh Publishing, 2013. Vol. 1. S. 207-253; Manistina, N. In. Innovative technologies and equipment for pharmaceutical industry / N. In. Manistina, Y. Mishina, S. B. Alves. M.: Publishing house of the BINOMIAL, 2012. Vol. 1. S. 81-171; Gorodnichev, V. I. Optimization of the process of granulation of pharmaceutical powders in a fluidized bed / Gorodnichev V. I., Hani M. El-Banna, B. V. Andreev // Chem.-Pharm. log. 1980. No. 10. S. 72-77].

Known solid dosage form comprising a therapeutically effective amount of aliskiren [us Pat. 2480210 OF THE RUSSIAN FEDERATION, IPC A61K 31/16, A61K 31/137, A61K 9/20, A61K 9/30, A61J 3/10, A61P 9/10, A61P 9/00 RF. SOLID ORAL DOSAGE FORM AND METHOD OF TREATMENT].

Aliskiren-hemifumarate is part of their chemical structure is monoamide ethylene-1,2-dicarbonic�th acid, classified in the same class of drugs as the substance of the claimed composition. Aliskiren is recommended, including for the treatment of diseases of the cardiovascular system. When creating oral forms, including traditional excipients, for both active substances (aliskiren and claimed) encountered similar difficulties associated with the creation of medicines that meet the requirements of the Pharmacopoeia.

The oral form according to the patent 2480210 and its manufacturing method, selected as a prototype for the claimed group of inventions.

In the process of developing tablets with 4-((3-oxo-3-ethoxypropanol)amino)benzoic acid it was found that the introduction of the most famous fillers and the use of traditional technology does not ensure compliance with at least the two most important indicators of tablets, namely, sufficient strength of the tablet and release of the active substance required by the global Fund XI and XII, as well as major foreign Pharmacopoeias (USP, BP, EP).

Regarding durability:

APABC represents hydrophobic particles, which practically does not possess lipomastia under pressure, i.e., moldability. Because the dose of active substance in the tablet should be quite high, about 300 mg/tab., i.e., in tablet weight 50-70% of the known binders are not both�workers receive tablets and granules of sufficient strength; the strength of the tablets manufactured using known binders (starch, gelatin, HPMC, PVP, etc.), does not exceed 2 kg. Such weak tablets crumble when you try applying a film of the shell and at packing.

Versus release:

APABC practically not soluble and is not wetted by water. Therefore, in determining release on the test "Dissolution" for 45 minutes passes from the tablets in a solution of less than 65% of the active substance that does not meet the requirements of the Pharmacopoeia.

The objective of the proposed group of inventions is to provide a composition and method for producing a pharmaceutical composition in the form of tablets containing as active substance APABC that would ensure the release of at least 75% of the active substance 45 minutes in accordance with pharmacopoeial requirements and have adequate strength for subsequent technological operations, i.e. at least 6 kg or tablet.

The task is solved in that the pharmaceutical composition with anti-ischemic and antioxidant activity in the form of tablets or capsules containing 4-((3-oxo-3-ethoxypropanol)amino)benzoic acid as the active component, amine-containing compound selected from the group trometamol, meglumine, L-lysine, lactose, microcrystalline cellulose, calcium stearate and other pharmaceutically when�mimie fillers, moreover, the content of 4-((3-oxo-3-ethoxypropanol)amino)benzoic acid in the composition is from 40 to 80 wt. % and 1 mol of 4-((3-oxo-3-ethoxypropanol)amino)benzoic acid has from 0.05 to 0.25 mol of the specified amine compounds.

The problem is solved also by the fact that pharmaceutical composition as a pharmaceutically acceptable excipients include sucrose, magnesium carbonate, starch, mannitol, polyvinylpyrrolidone, disintegrant, anti-friction and sliding substances, adopted in pharmaceutical technology.

The problem is solved also by the fact that the pharmaceutical composition may be in the form of tablets or capsules with a therapeutically effective dose of 4-((3-oxo-3-ethoxypropanol)amino)benzoic acid.

The problem is solved also by the fact that the method of obtaining pharmaceutical compositions with anti-ischemic and antioxidant activity includes dipping and mixing the components, granulation, drying, pressing of tablets or filling into hard gelatin capsules, and 4-((3-oxo-3-ethoxypropanol)amino)benzoic acid and the specified amine compound, taken in a molar ratio of from 1:0.05 to 1:0.25, and pre-mixed, the mixture is moistened aqueous or alcoholic solution of a bonding agent, then to the damp mixture is added pharmaceutically acceptable excipients, such �the number, to ensure that the content of 4-((3-oxo-3-ethoxypropanol)amino)benzoic acid a total weight of 40 to 80 mass%, the mixture is then granulated, dried and get a tablet or capsule according to known technology.

The problem is solved also by the fact that the binder agent used starch-sugar paste or alcoholic solution of polyvinylpyrrolidone.

The essence of the proposed inventions

The research unexpectedly it was found (and this solves the problem) that when mixed APABC with an organic compound containing an amino group, for example trometamol, N-metilglyukaminom or L-lysine, and subsequent hydration of the mixture water-alcohol solution or water, then followed by the addition of auxiliary substances - lactose, MCC, mannitol, sodium bicarbonate, magnesium carbonate or other pharmaceutically acceptable fillers - obtained wet mass. After drying and granulating the mass becomes a good flowability, it is easily pressed pills, or possible packing of the granules in the capsule according to known technology. During compaction obtained strong pills, suitable for filling and coating. Tablets may be coated with a protective or decorative shell in the coater or in a fluidized bed apparatus by known methods.

The release of active substances from t�of bleak, obtained by the proposed method is 80-90% in 45 minutes, which corresponds to the pharmacopoeial requirements.

Significant was the relative molar ratio APABC and amine-containing compounds.

If you enter less than 5 mol.% amine compound to 1 mol APABC, the tablets obtained is not strong enough, and the release does not exceed 65% for 45 minutes.

If in the to enter more than 25 mol.% amine compound to 1 mol APABC, it is obtained a viscous, difficult to granulation and drying, low-tech processing.

Without claiming to be a theoretically grounded description of the processes, it has been experimentally found that the combination of 5÷25 mol.% APABC with the amine compound is necessary and sufficient to make the granulate and the tablet lot of positive technological properties that provide good moldability and release the active substance.

It was also found that the content APABC in tablet weight should be no more than 80%. In the case of higher content APABC tablet weight bad press, the tablets become unstable. In addition, tablets containing APABC exceeding 80%, decay for more than 30 min, which does not meet the requirements of the Pharmacopoeia in disintegration. The decrease in the content�of APABC in tablet weight below 40% is impractical due to excessive increase in average weight of the tablets.

The technical result of the claimed invention are:

A composition and method of its receipt.

The release of the active substance from the tablet in an amount of not less than 75% in 45 min, which corresponds to pharmacopoeial requirements;

The strength of tablets is not less than 6 kg per 1 tablet that provides the possibility of subsequent technological operations - the application of film coating, packaging automatic lines.

The achievement of the technical result is proved by the determination of strength, dissolution and disintegration of tablets in accordance with pharmacopoeial methods.

The invention is characterized by the following examples.

As follows from the data presented in tables, the most durable and with high rates of release were samples containing from 40 to 80 mass percent APABC in composition and 10-20 mole percent amine compound relative to APABC. In the lower limit of the content of aminosidine - 5% or less, strength of the tablet begins to decline, and also reduced the % release of active agent. In case of absence of aminoguanidine (sample 9) of the tablets obtained is very weak, and the degree of release is reduced to 60% or less.

When introduced into the composition Bo�her 25 mol.% aminosidine to APABC mass during mixing and hydration becomes very viscous, difficult to granulation and drying. As a consequence, the losses increase, the process becomes low-tech and difficult-to-reproduce.

Examples of the method of producing a pharmaceutical composition with APABC in pill form

Example 1. Obtaining cores of tablets APABC with granulation aqueous starch paste.

In a mortar portions add 60 g APABC to 2 g of trometamol, mixing thoroughly after adding each portion. To the dry mixture are added 20 g of starch-sugar paste containing 2 g of sugar beet and 2 g of potato starch. The mass was thoroughly mixed for homogeneity wipe through a sieve with hole size of 3.5 mm.

Then to the wet weight gain of 15 g of lactose, 7 g of microcrystalline cellulose and 10 g of sodium hydrogen carbonate. The resulting mixture is forced through a sieve with a mesh width of 2.5 mm was spread on a pan and dried in a vacuum oven at (60-70)°C to a residual moisture content of 2-4%.

The dried granulate is calibrated by rubbing through a sieve with openings of 1.0-1.5 mm. To the obtained powder add 1 g of polyplasdone XL, 1 g of calcium stearate and dusted in the mixer for dry powders for 30 min.

The mixture is compressed biconvex tablets with a diameter of 11 mm and average weight (0,500±0,025).

Output is 96 g (192 t�of blecki). Properties of the obtained tablets are shown in table.2, example 3.

Example 2. Obtaining cores of tablets APABC with granulation alcoholic solution of PVP.

In a mortar portions add 50 g APABC to 7.5 g L-lysine, mixing thoroughly after adding each portion. To the dry mixture is added 40 g of a 20% ethanolic PVP solution containing 8 g of PVP. The mass is thoroughly mixed and forced through a sieve with a hole size of 3.5 mm.

Then to the wet mass is added 10 g of lactose, 10 g of microcrystalline cellulose, 5 g of magnesium carbonate and 6.5 g of sodium hydrogen carbonate.

The resulting mixture is forced through a sieve with a mesh width of 2.5 mm was spread on a pan and dried in a vacuum drying Cabinet at 50°C to a residual moisture content of 2-3%.

The dried granulate is calibrated by rubbing through a sieve with openings of 1.0-1.5 mm. To the obtained powder add 2 g of polyplasdone XL, 1 g of calcium stearate and dusted in the mixer for dry powders for 30 min.

The mixture is compressed biconvex tablets with a diameter of 12 mm and average weight (0,600±0,030).

The output representing 91.2 g (152 tablets). Properties of the obtained tablets are shown in table.2, example 2.

Example 3. Obtaining cores of tablets APABC with granulation aqueous starch paste and drying in a fluidized bed.

In a mortar portions add 100 g APABC to 6.0 g L-lysine, tih�tive stirring after adding each portion. To the dry mixture is added 40 g of starch-sugar paste containing 6 g of sugar beet and 4 g of potato starch. The mass is thoroughly mixed and forced through a sieve with a hole size of 3.5 mm.

Then the wet mass was added 18 g of lactose, 20 g of microcrystalline cellulose, 20 g of magnesium carbonate and 20 g of sodium bicarbonate and stirred until homogeneity.

The resulting mixture is forced through a sieve with a mesh width of 2.5 mm. the Wet granulate is placed in a chamber of a fluidized bed dryer and dried to a residual moisture content of 2-3%.

The dried granulate is calibrated by rubbing through a sieve with openings of 1.0-1.5 mm. the obtained powder was added 4 g of polyplasdone XL, 2 g of calcium stearate and dusted in the mixer for dry powders for 30 min.

The mixture is compressed biconvex tablets with a diameter of 12 mm and average weight (0,600±0,030).

The output is 188 grams (313 pills). Properties of the obtained tablets are shown in table. 2, example 7.

Example 4. Anti-ischemic action

The anti-ischemic effect of 4-((3-oxo-3-ethoxypropanol)-amino)-benzoic acid (hereinafter APABC) in comparison with prescription anti-ischemic drugs studied in a model of myocardial infarction, is accomplished by ligation of the left coronary artery in rats.

The most reliable differences between the groups were�charged on: 1) the size of the left atrium, 2) end-systolic and diastolic dimensions of the left ventricle, 3) the size of necrosis in the myocardium.

Differences between groups of intact animals and negative controls were reliable. The lack of stretching of the left atrium in the application of effective doses and modes of administration APABC says about the decrease in the severity of pathological changes in the myocardium due to acute and chronic heart attacks. So, after intragastric administration of Trimetazidine and APABC showed improvement compared with the negative control, with the trend towards greater efficiency APABC, a value approaching that of intact rats.

End-systolic dimensions of the left ventricle (Xrls) and end-diastolic dimension (Cdrls), characterizes the factor of left ventricular contractility of the myocardium, and therefore its pumping function. Differences between groups of intact animals and negative controls were reliable. Amid intragastric administration APABC observed significant differences compared with those obtained from untreated rats.

As can be seen from table 4, in the control series experiment� the size of the zone of necrosis in rats amounted to 22.0±2.0% of total myocardial mass. The size of the zone of ischemia in this time period were equal 34,0±2.6% of the total myocardial mass. Thus, the size of the zone of necrosis was 68,0+4.3% the size of the zone of ischemia.

The latter figure according to modern concepts is one of the important characteristics of ischemic alteration of the myocardium, since it does not depend on the level of ligation of the coronary artery and thus is considered as the most stable value. APABC at a dose of 60 mg/kg reduced the size of the necrosis zone to 39+9.4% of the ischemia that significantly more of this index in the group of the drug comparison of Meldonium (gr. 5).

Example 5. Antioxidant action

Poisoning CCl4are the classic model of peroxidation of liver damage. Activation of lipid peroxidation when administered CCl4judged by the accumulation of peroxidation products - diene conjugates (DC), lipid hydroperoxide (HP) and malondialdehyde (MDA) in blood and liver of rats.

As can be seen from the above data (table. 7), APABC has a strong antioxidant effect, of the same order as methylethylidene and classical antioxidant - tocopherol acetate.

Thus, when studying specific actions APABC installed:

1. Antisemite�cue effect APABC and pharmaceutical compositions based on it is manifested in the form of the positive effects on systolic dimensions of the left atrium and ventricle, the absence of myocardial hypertrophy, improve blood flow in the pulmonary artery. The infusion of APABC were detected phenomena such as aneurysm, synergy, akinesia, there was no thrombus formation.

2. The infusion of APABC observed acceleration of repair processes of the myocardium and reducing areas of necrosis, increased uptime, improved contractile activity of the myocardium.

3. The values of antioxidant activity of the tested substance APABC and farbkomposition on its basis can be attributed to this compound to substances with a moderate antioxidant activity.

Example 6. Determination of acute toxicity of 4-((3-oxo-3-ethoxypropanol)amino)benzoic acid (hereinafter APABC)

Investigations were carried out on outbred mice and rats in accordance with accepted international rules and protocols.

The experiment is installed:

- intraperitoneal substances white outbred mice, males and females, the magnitude of LD50amounted to 2440 mg/kg;

- after intragastric administration of a substance white outbred mice, males and females, the magnitude of LD50exceeded 5010 mg/kg;

- intraperitoneal substances white mongrel rats, males and females, the magnitude of LD50amounted 6050 mg/kg;

- after intragastric administration of a substance white mongrel Kry�am males and females, the magnitude of LD50amounted to 8900 mg/kg.

In accordance with the gradation Hodge and Sterner test pharmaceutical substance can be classified as low-toxic and non-toxic substances.

With the introduction of pharmaceutical compositions containing APABC, the dose calculation was made in terms of substance.

Studied specific anti-ischemic and antioxidant activity of the finished dosage form (tablets) malonic acid derivative (APABC) to effective dose for animals (tab. 2). The powder of crushed tablets for suspension were dissolved in purified water and administered orally (intragastrically).

Formed groups of 30 animals:

1L - group lonaprisan animals (intact control) - were dissected thorax of the animal followed by suturing similar in other groups of conditions, but without ligation of the left coronary artery;

2L - negative control group of animals with the simulated pathology, but left untreated);

3L - group of animals, which were injected intraperitoneally drug comparison of Trimetazidine with therapeutic in rats the dose of 6 mg/kg for 60 days;

4L - group of animals that were administered the test substance intragastrically efficient results of the study substance dose within 60 days;

5L - a group of animals that were administered oral medication comparison Meldonium in therapeutic in rats a dose of 85 mg/kg for 60 days.

Anti-ischemic effect is manifested in the form of the positive effects on systolic dimensions of the left atrium and ventricle, absence of myocardial hypertrophy, improve blood flow in the pulmonary artery. During administration of the drugs were discovered phenomena such as aneurysm, synergy, akinesia, there was no thrombus formation. Based on the data in the 29th and 60th day of treatment, treatment within 28 days can be considered sufficient, which is consistent with the timing of the main stages of post-infarction remodeling of the myocardium.

Anti-ischemic and antioxidant activity complies with SFF as such in terms of the released substance.

We studied the safety of the finished dosage form of a derivative of malonic acid in acute and chronic experiments. The obtained values of the LD50in mice and rats of different sex by oral administration allow us to classify the tested drug to drugs with low toxicity. The magnitude of LD50exceed 2000 mg/kg.

Long-term (16 weeks) introduction of final dosage form (tablets) does not change the basic parameters of experimental animals of different sex - no changes in the composition of peripheral to�AVI, biochemical parameters of hemostasis, clinical parameters urine. During administration of the test drug does not change the dynamics of body weight, rates of cardiovascular, urinary and Central nervous systems. Pathological and histological examination did not reveal any injury to the organs and tissues of experimental animals. Delayed toxic effects were absent.

1. Pharmaceutical composition with anti-ischemic and antioxidant activity in the form of tablets or capsules, characterized in that it contains 4-((3-oxo-3-ethoxypropanol)amino)benzoic acid as the active component, amine-containing compound selected from the group trometamol, meglumine, L-lysine, lactose, microcrystalline cellulose, calcium stearate and other pharmaceutically acceptable excipients, wherein the content of 4-((3-oxo-3-ethoxypropanol)amino)benzoic acid in the composition is from 40 to 80 wt.%, as per 1 mol of 4-((3-oxo-3-ethoxypropanol)amino)benzoic acid has from 0.05 to 0.25 mol of the specified amine compounds.

2. Pharmaceutical composition according to claim 1, characterized in that the pharmaceutically acceptable excipients include sucrose, magnesium carbonate, starch, mannitol, polyvinylpyrrolidone, disintegrant, anti-friction and high-speed�czasie substances adopted in pharmaceutical technology.

3. Pharmaceutical composition according to any one of claims.1, 2, characterized in that is made in the form of tablets with a therapeutically effective dose of 4-((3-oxo-3-ethoxypropanol)amino)benzoic acid.

4. Pharmaceutical composition according to any one of claims.1, 2, characterized in that is made in the form of capsules containing a therapeutically effective dose of 4-((3-oxo-3-ethoxypropanol)amino)benzoic acid.

5. A method of obtaining a pharmaceutical composition with anti-ischemic and antioxidant activity according to claim 1 or 2, including dipping and mixing the components, granulation, drying, pressing of tablets or filling into hard gelatin capsules, characterized in that 4-((3-oxo-3-ethoxypropanol)amino)benzoic acid and the specified amine compound, taken in a molar ratio of from 1:0.05 to 1:0.25, and pre-mixed, the mixture is moistened aqueous or alcoholic solution of a bonding agent, then to the damp mixture is added pharmaceutically acceptable excipients in an amount to ensure that the content of 4-((3-oxo-3-ethoxypropanol)amino)benzoic acid a total weight of 40 to 80 wt.%, the mixture is then granulated, dried and get a tablet or capsule according to known technology.

6. A method according to claim 5, in which the binder agent used starch-sugar Claeys�EP or alcoholic solution of polyvinylpyrrolidone.



 

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2 dwg, 12 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and can be used as a hepatotrophic, lipotropic agent in gastroenterology, as well as for treating cardiac and cerebral atherosclerosis, in neurology in the lower extremity artery diseases (endarteritis). The agent contains tabletted powders of diisopropylammonium dichloroacetate, microcrystalline cellulose, lactose and excipients presented by Aerosil, Primogel and calcium stearyl fumarate.

EFFECT: agent possesses no toxicity, has the high adsorption properties, the apparent anti-inflammatory action, and provides metabolism and the liver regeneration.

3 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to heterocyclic compound - 6-methyl-5-morpholynomethyl-1-(thiethan-3-yl)pyrimidine-2,4(1H,3H)-dione of formula 6-methyl-5-morpholynomethyl-1-(thiethan-3-yl)pyrimidine-2,4(1H,3H)-dione of formula: .

EFFECT: novel compound, possessing antioxidant activity, is obtained.

2 cl, 6 tbl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, and concerns a pharmaceutical composition for treating gastroduodenal ulcer in the form of tablets, capsules or gel, containing therapeutic agents and a consistency base applicable for each dosage, wherein the therapeutic agents are as follows: recombinant interferon specified in a group: recombinant interferon alpha, recombinant interferon beta, recombinant interferon gamma; antiseptics; amino acids specified in a group: arginine, histidine, lysine, cysteine, methionine, glutamic acid; and antioxidants specified in a group: beta-carotene, vitamin C, vitamin E.

EFFECT: invention has the integrated body effect promoting faster healing of the mucosal defect accompanying the aggravated gastroduodenal ulcer and preventing recurrences, including by the eradication effect.

6 cl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, and concerns a pharmaceutical composition in the form of tablets for oromucosal administration in treating infectious-inflammatory oropharyngeal diseases. The composition contains recombinant interferon specified in a group: recombinant interferon alpha, recombinant interferon beta, recombinant interferon gamma; amino acid specified in a group: arginine, histidine, glycine, glutathione, lysine, methionine, cysteine; an antiseptic, a preserving agent, flavours specified in a group: tea tree oil, eucalyptus leaf oil, mint leaf oil and a consistence base.

EFFECT: invention makes the composition applicable in fragile and frequently ill patients for reducing a disease recurrence.

7 cl, 1 ex

FIELD: food industry.

SUBSTANCE: biologically active food additive strengthening the organism adaptive power and body defences and having anti-inflammatory and antioxidant activity contains vegetal origin components represented by a complex extract of devil's-club root, Rhaponticum carthamoides root, Hedysarum neglectum Ledeb root, celery roots and leaves, rhodiola rosea root, Japanese angelica tree roots, boschniakia rossica roots, Hungarian sainfoin herb, magnolia-vine fruits; additionally the additive contains chitosan, trepang fermentative hydrolysate, ascorbic acid, taurine, glutathione, nicotinamide, vitamin B1, vitamin B2, vitamin B6, vitamin B12, folic acid, anhydrous calcium chloride, magnesium chloride, zinc chloride, bee honey at preset ingredients ratio.

EFFECT: biologically active food additive promotes effective strengthening of the organism adaptive power and body defences and human aging retardation.

4 tbl, 6 ex

FIELD: medicine.

SUBSTANCE: invention relates to medical radiology and can be used for prevention of cerebral form of acute radiation sickness. Claimed is application of officinal drug pyrazinamide as medication for prevention of cerebral form of acute radiation sickness. Pyrazinamide has been used for treating tuberculosis.

EFFECT: preventing in 100% of cases development of early temporary incapacity in case of irradiation in dose 200 Gy, improvement of indices of behavioral and research activities in irradiated animals, in reduction of frequency of motor disorders, reduction of frequency and expression of convulsive-hyperkinetic syndrome and 9,5 fold increase of average life expectancy of irradiated animals Pyrazinamide is not inferior to drug - nicotinamide prototype in efficiency of radioprotective action.

4 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and represents a composition possessing the antioxidant and antibacterial activity and containing lithium ascorbate, differing by the fact that it additionally contains lithium benzoate in the following proportions, wt %: lithium ascorbate - 50; lithium benzoate - 50.

EFFECT: invention provides extending the range of antioxidants with antibacterial activity possessing normothymic activity.

1 ex, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutics, in particular a pharmaceutical composition in the form of a peroral drug form is described. The composition includes rebamipide as an active ingredient and a pharmaceutically acceptable carrier. Rebamipide is contained in an amount from 0.5 to 50 mg/kg, preferably from 0.6 to 6 mg/kg.

EFFECT: application of the rebamipide-based pharmaceutical composition for the prevention and treatment of arthrosoarthritis.

5 cl, 3 dwg, 1 tbl, 1 ex

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