Method for entero- and pancreactoprotective action of non-steroid anti-inflammatory preparations

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to experimental medicine and gastroenterology, and can be used for the entero- and pancreatoprotective action of non-steroid anti-inflammatory preparations in simulating the gastric ulcer and/or pancreatitis experimentally. To this effect, the simulation is preceded by administering courses of Ketanov, Celebrex or Ketonal. The preparations are administered parenterally. A dose for the first three days is 2.5-3.1 mg/kg. A dose for the following three days is 1.5-2.4 mg/kg. That is followed by four days in a dose of 0.5-1.4 mg/kg with the therapeutic course repeated 1.5-2 months later. For the first three days of the repeated course, a dose of the preparation makes 0.7-2.0 mg/kg. A dose for the following three days makes 2.1-2.6 mg/kg. And for the final four days, a dose of the preparation makes 2.7-3.1 mg/kg.

EFFECT: method provides the effective entero- and pancreatoprotective action of the non-steroid anti-inflammatory preparations in simulating the gastric ulcer and/or pancreatitis experimentally with reducing the toxicity of the exposure.

3 ex

 

The invention relates to medicine and can be used as a way of entero - and pancreatoblastoma of action of nonsteroidal anti-inflammatory drugs.

Nonsteroidal anti-inflammatory drugs (Ketanov, Ketonal, celebrex) are selective inhibitors of cyclooxygenase-2 (COX-2). COX-2 is induced in response to inflammatory process that leads to the synthesis and accumulation of inflammatory prostanoids (in particular, PGE) that, in turn, causes inflammation, swelling and pain. Prostaglandins enhance the feeling of pain, initiating inflammation of the tissue at the site of damage, so along with anti-inflammatory effects these drugs have a pronounced analgesic effect. Celebrex (celecoxib) did not inhibit COX-1, therefore, does not affect prostanoids synthesized by activating COX-1, and thus, does not prevent the development processes associated with the action of COX-1 in the tissues (ulcerative lesions of the stomach and duodenal ulcers, perforation, obstruction, lack of inhibition of COX-2-dependent platelet aggregation).

A method of treating pain syndrome nonsteroidal anti-inflammatory drugs, taken as an analogue (1 - Burian M, Geisslinger G. Clinical pharmacology of the selective COX-2 inhibitors. Orthopade. 2003 Dec; 32(12):1078-87).

A method of treating balewa�about syndrome inflammatory drugs by immersing the tail in experimental animal slurry, containing dimethyl sulfoxide and test anti-inflammatory drug (2 - Karadas V. et al. Additive interaction of intraperitoneal dexmedetomidine and topical nimesulide, celecoxib, and DFU for antinociception. Eur J Pharmacol. 2007 Nov 5; 556(1-3):62-8). This method is adopted for the prototype. The sulfoxide to the nature of the experience in an acute - neurotropic drug. Causes symptoms of CNS excitation (increased reflex excitability, aggressiveness, clonic convulsions), and the depression of nerve function (slowing of the breathing, weakness, lateral position). Dimethyl sulfoxide has hemolytic properties, causes hemolysis and hematuria. Increases thirst and urination. Dimethyl sulfoxide easily penetrates through all biological membranes.

However, the prototype method has limited effectiveness of treatment of inflammatory diseases of the tract that occur with inflammation, and apply the drug is toxic.

The purpose of the invention is to improve the treatment of gastric ulcers and duodenal ulcers and pancreatitis nonsteroidal anti-inflammatory drugs while reducing toxicity.

The technical result is achieved in that before modeling courses of introduction of salts of celebrex or ketone, wherein the drugs are administered parenterally, and during the first three days of the course at a dose of 2.5-3.1 mg/kg, with subsequent entered�eat for three days at a dose of 1.5-2.4 mg/kg, during the next four days at a dose of 0.5-1.4 mg/kg, followed by a repetition of the course in 1.5-2 months, and the first three days of a repeated course dose of 0.7-2.0 mg/kg, following three days, the dose is 2.1-2.6 mg/kg, the final four days dose of 2.7-3.1 mg/kg.

The method is implemented as follows.

Experiments on the control group of animals (no NSAIDs).

Experiments were conducted on 15 Wistar rats weighing 200-250 g.

Model of gastric ulcer and duodenal ulcer and pancreatitis created by applying a 100% acetoacetic acid on the serosa of the stomach on the border of antral and fundic departments and serosa bulbar division of the duodenum; the model of pancreatitis was created by the introduction of 0.05-1.0 ml of 100% acetoacetic acid into the pancreatic duct.

Background the frequency of slow waves EMA duodenum was 18.5±0.9 min, amplitude of 0.23±0.03 mV. Modeling of stomach ulcers and ulcer 12 duodenal ulcer slightly modifies the testimony of slow wave activity in duodenum 12 on the 10th day of the model: the frequency of slow waves EMA duodenum of 19.1±1.3 min and amplitude of 0.21±0.05 mV. Thus, on the 10th day of the EMA model 12 duodenal ulcer were not significantly changed.

Background the frequency of slow waves EMA of pancr�interactive-duct was 11.7±0.6 min, the amplitude of 0.17±0.03 mV. Modeling pancreatitis led to a change in electric activity of the pancreatic duct on the 10th day of the model: the frequency of the slow waves is increased by 10-15%, the amplitude increased by 25-30%.

Morphological study of gastric ulcers and duodenal ulcers on the 10th day of the model showed that the wall of the ulcer is detected detritus, primary cancer of the stomach is filled with a viscous secret, cystic expanded; venous vessels sharply dilutionary, filled with blood; the villi of the duodenum deformed and infiltrated lymphoid cells, granulation tissue is formed, the vessels are dilated, there is stasis of blood.

Morphological examination of pancreatic tissue on the 10th day of the simulation pancreatitis revealed swelling of the slices, increase midorikawa and intralobular connective tissue. Thin intralobular connective tissue layer is shared by a small group of cells. In the interlobular space are dilated veins with the regional standing of red blood cells. The density of endocrinocytes in the islets reduced: detected extended intervals between the cells is filled with connective tissue with a single capillaries. Found small clusters of damaged cells. Marked degeneration of the islets of Langer�ANSA. In pancreatic duct detected the accumulation of proteinaceous secret, which hinders its outflow into the duodenum and creating conditions for the development of pancreatitis.

The experimental group of animals with the introduction of NSAIDs.

Prior chronic administration of salts increases the electromotive activity 12-taperstry guts on the 10th day of the model: the frequency increases to 21.6±2.3 V min (16.2 per cent), the amplitude - to 0.47±0.05 mV (104,3%). Thus, Ketanov stimulates motor activity of the duodenum.

Prior chronic introduction of ketone increases the frequency of slow waves EMA duodenum on the 10th day of the model: to 21.8±2.3 V min (11.8 per cent) and increases the amplitude - to 0.54±0.07 mV (134,8%). Thus, Ketonal changes chronoinotropic relationship of the contractile activity of the duodenum by increasing the amplitude of the local response.

Prior chronic introduction of celebrex increases the frequency of slow waves EMA duodenum on the 10th day of the model: to 27.0±3.3 V min (17%) and the amplitude of 0.7±0,08 mV (203%). That is, celebrex enhances and speeds up slow-wave electromotive activity, enhancing the motility of the duodenum in General. Thus, the electromotive activity of the small intestine in response to chronic treatment with non-steroidal protivovospalitel�'s preparations characterized by an increase in peak-frequency characteristics of slow-wave activity.

Morphological study of gastric ulcer and duodenal ulcer in advance of the introduction of non-steroidal anti-inflammatory drugs have shown that drugs have gastroprotective effect by improving the functioning of the gastric glands, restoration of blood supply to the affected area, which contributes to more rapid epithelialization of the ulcer. Duodenoplasty the effect of chronic administration of nonsteroidal anti-inflammatory drugs is expressed in a more pronounced development of scar tissue and epithelialization of the ulcer, the restoration of brunerovy glands, as well as in the normalization of the diameter of the vessels of the submucosa and muscular layer, which leads to the optimization of the electric activity of the duodenum with the chronic administration of nonsteroidal anti-inflammatory drugs.

Morphological study of the tissues of the pancreas intestine in advance of the introduction of non-steroidal anti-inflammatory drugs and simulation of pancreatitis have shown that drugs have pancreatoblastoma action by improving the functioning of Associacao and endocrinocytes, prevent the development of connective tissue, improving blood supply to the affected area and the liberation of the lumen of the duct from elm�wow secret what contributes to a more rapid restoration of the functioning of the gland. Entero - and pancreatoblastoma action is determined by the activation electromotor activity of the pancreatic duct: the frequency of the slow waves is increased by 20-30%, the amplitude increased by 40-60%.

The method further explain examples of its implementation.

Example 1.

The rats of Wistar line, weighing 200 g of previously injected intramuscularly nonsteroidal anti-inflammatory drug, and during the first three days of the course at a dose of 2.5 mg/kg, followed by an introduction in the course of three days at a dose of 1.5 mg/kg, during the next four days at a dose of 0.5 mg/kg, followed by a repetition of the course in 1.5 months, and the first three days of a repeated course dose of 0.7 mg/kg, following three days dose of 2.1 mg/kg, the final four days dose of 2.7 mg/kg. Next, in nematalosa anesthesia (40 mg/kg intramuscularly) laparotomy was performed and recorded motor activity of the stomach and duodenum and pancreatic duct using silver electrodes with a contact surface, 1.5 mm2.

Model of gastric ulcers created by applying a 100% acetoacetic acid on the serosa of the stomach on the border of antral and fundic departments; the model of duodenal ulcer POPs�avals by applying 100% acetoacetic acid on the serosa of bulbar division of the duodenum; model of pancreatitis was created by injecting 0.05 ml of 100% acetoacetic acid into the pancreatic duct.

Background the frequency of slow waves EMA duodenum was 17.6 per minute, the amplitude - 0.2 mV. Prior chronic administration of salts increases the electromotive activity: frequency increased to 19.7 min (12%), the amplitude - to 0.42 mV (104%, p<0,05). That is Ketanov stimulates motor activity of the duodenum in the simulation ulcers.

Chronic introduction of ketone increases the frequency of slow waves EMA duodenum when modeling ulcers - to 19.8 per minute (more than 12.5%) and increases the amplitude - to 0.54±0.07 mV (more than 170%, p<0,05). That is, Ketonal changes chronoinotropic relationship contractile activity of duodenal ulcer gastric ulcer and duodenal ulcer.

Chronic introduction of celebrex at a dose of 2.5 mg/kg increases the frequency of slow waves EMA duodenum to 26.4 min (50%, p<0.05) and the amplitude to 0.7 (204,3%), p<0.01). Thus, celebrex enhances and speeds up slow-wave electromotive activity, enhancing the motility of the duodenum in General.

That is, the electromotive activity of the small intestine in the simulation of ulcers of the stomach and duodenum in response to chronic treatment with preparations characterized by an increase in the amplitude-frequency characteristics of slow-wave activity.

Modeling of gastric ulcers and duodenal ulcers and pancreatitis consistent application of salts of cetinale, celebrex leads to activation of electromotive activity of bulbar division of the duodenum: the frequency of the slow waves is increased by 12%, the amplitude is doubled; EMA pancreatic duct in the simulation pancreatitis action of nonsteroidal anti-inflammatory drugs leads to activation of the electric activity of the pancreatic duct: the frequency of the slow waves is increased by 20%, the amplitude increased by 43%.

Modeling of gastric ulcers and duodenal ulcers and pancreatitis action of nonsteroidal antiinflammatory drugs was accompanied by increased motor activity of the duodenum and pancreatic duct.

Morphological study of gastric ulcers and duodenal ulcers showed that the edges of the ulcer (stomach ulcer) saped, the bottom is made with gray patina, the main glands of the stomach is filled with a viscous secret, cystic expanded; Vienna submucosa and muscular layer sharply dilutionary, filled with blood; the villi of the intestine (ulcer of duodenum) deformed and infiltrated lymphoid cells, blood vessels dilated. Morphological study of the pancreas in simulated�and pancreatitis showed partial degradation of exogenous and endocrinocytes, the extension of the veins with blood stasis and excess of connective tissue.

Morphological study of gastric ulcers and duodenal ulcers, and Pancreatin in comparable terms in advance of the introduction of non-steroidal anti-inflammatory drugs have shown that drugs have gastroprotective effect by improving the functioning of the gastric glands, restoration of blood supply to the affected area, which promotes more rapid healing of ulcers. Duodenoplasty the effect of chronic administration of NSAIDs is more pronounced development of scar tissue and epithelialization of the ulcer, the restoration of brunerovy glands, as well as in the normalization of the diameter of the vessels of the submucosa and muscular layer, thereby increasing the electromotive activity of the duodenum with the chronic administration of nonsteroidal anti-inflammatory drugs. Pancreatoblastoma the effect of chronic administration of nonsteroidal anti-inflammatory drugs is the preservation of pancreatic tissue and its normal blood supply, the normalization of the passage of secretion by the pancreatic duct.

Entero - and pancreatoblastoma action is determined by the activation electromotive AK�Yunosti pancreatic duct: the frequency of slow waves increased from 10 to 12 in min (20%), the amplitude increased from 1.0 to 1.4 mV (40%).

Thus, non-steroidal anti-inflammatory drugs for parenteral administration have gastro-, entero - and pancreatoblastoma action.

Example 2.

The rats of Wistar line weighing 250 g drugs were administered parenterally during the first three days of the course at a dose of 3.1 mg/kg, followed by an introduction in the course of three days at a dose of 2.4 mg/kg, during the next four days at a dose of 1.4 mg/kg, followed by a repetition of the course in 2 months, and the first three days of a repeated course, the medication dosage is 2.0 mg/kg, following three days, the dose is 2.6 mg/kg, the final four days dose of 3.1 mg/kg. Next, in nematalosa anesthesia (40 mg/kg intramuscularly) laparotomy was performed and recorded motor activity of the stomach, the duodenum. Motor activity of the stomach and the rising of the duodenum were recorded using silver electrodes with a contact surface, 2.0 mm2.

Model of gastric ulcers created by applying a 100% acetoacetic acid on the serosa of the stomach on the border of antral and fundic departments; the model of duodenal ulcer created by applying a 100% acetoacetic acid on the serosa of bulbar Department dwenadzatiperstnuu�th guts. model of pancreatitis was created by injecting 0.1 ml of 100% acetoacetic acid into the pancreatic duct.

Background the frequency of slow waves EMA duodenum was 17.6 per minute, the amplitude - 0.2 mV. Chronic introduction of salts increases the electromotive activity: frequency increased to 26.4 min (50%), amplitude - 0.61 mV (204%). That is Ketanov stimulates motor activity of the duodenum.

Chronic introduction of ketone increases the frequency of slow waves EMA - from 18.4 to 27.2 min (48%) and increases the amplitude - from 0.26 to 0.79 mV (203%). That is, Ketonal changes chronoinotropic relationship of the contractile activity of the duodenum.

Subsequent chronic introduction of celebrex increases the frequency of slow waves EMA from 19.4 to 28.9 min (49%) and range from 0.24 to 0.73 (203%). Thus, celebrex enhances and speeds up slow-wave electromotive activity, enhancing the motility of the duodenum in General.

That is, the electromotive activity of the small intestine in response to chronic treatment with non-steroidal anti-inflammatory drugs characterized by an increase in the amplitude-frequency characteristics of slow-wave activity.

Modeling of gastric ulcers and duodenal ulcers and pancreatitis successive approx�tion of salts cetinale, celebrex leads to activation of motor activity of the stomach and bulbar division of the duodenum: the frequency of the slow waves is increased to 50%, the amplitude increased more than twice.

That is, the modeling of duodenal ulcer in the background of the action of non-steroidal anti-inflammatory drugs was accompanied by increased motor activity of the duodenum.

Entero - and pancreatoblastoma action is determined by the activation electromotor activity of the pancreatic duct: the frequency of slow waves increased from 10 to 13 min (30%), the amplitude is increased from 1 to 1.6 mV (60%).

Morphological study of gastric ulcers and duodenal ulcers has shown that the walls of the ulcer (stomach ulcer) covered with overlays of fibrin, the main ducts of the glands of the stomach is blocked viscous secret, end divisions cystic glands enlarged; the villi of the intestine (ulcer of duodenum) destroyed, periultseroznoy area infiltrated by lymphoid cells, venous vessels sharply dilutionary, filled with blood. Morphologically when modeling pancreatitis indicates the presence of a viscous protein secretion in duct, blood stasis in the vessels, disorganization Exo - and endocrinocytes.

Morphological study of gastric ulcer and duodenal ulcer in comparable terms in the condition�ies prior administration of nonsteroidal anti-inflammatory drugs showed what gastric glands ducts are free, the blood supply to the affected area restored. Chronic treatment with non-steroidal anti-inflammatory drugs leads to more rapid healing of duodenal ulcers, expressed in the form of development of scar tissue and epithelialization of the ulcer, restoration activities brunerovy glands, and also to normalize the diameter of the vessels of the submucosa and muscular layer. Chronic treatment with non-steroidal anti-inflammatory drugs leads to normalize the function of the Exo - and endocrinocytes, the release of the ducts from viscous proteinaceous secret.

Thus, non-steroidal anti-inflammatory drugs for parenteral administration have gastro-, entero-, and pancreatoblastoma action.

Example 3.

The rats of Wistar line weighing 250 g pre -, parenterally administered drugs Ketonal, Ketanov and celebrex, and during the first three days of the course at a dose of 3.0 mg/kg, followed by an introduction in the course of three days at a dose of 2.0 mg/kg, during the next four days at a dose of 1.2 mg/kg, followed by a repetition of the course of 50 days, and the first three days of a repeated course dose of 1.5 mg/kg, following three days, the dose is 2.5 mg/kg, the final four days dose 3.0 mg/kg. Next, in nematalosa drug�(40 mg/kg intramuscularly) laparotomy was performed and recorded motor activity of the stomach and duodenum. Motor activity of the stomach and the rising of the duodenum were recorded using silver electrodes with a contact surface, 1.7 mm2.

Model of gastric ulcers created by applying a 100% acetoacetic acid on the serosa of the stomach on the border of antral and fundic departments; model ulcers jejunum was created by applying a 100% acetoacetic acid on the serous membrane of the jejunum in the middle third.

Background the frequency of slow waves EMA jejunum on the background of ulcers of the stomach and the jejunum was 19.4 per minute, the amplitude of 0.23 mV. Chronic introduction of salts increases the electromotive activity: frequency increased from 19.4 to 25.4 min (31%), amplitude - from 0.26 to 0.66 mV (152%). That is Ketanov stimulates motor activity of jejunal ulcers of the stomach and the jejunum.

Chronic introduction of ketone increases the frequency of slow waves EMA - from 18.4 to 23.6 min (28%) and increases the amplitude - from 0.23 to 0.59 mV (157%). That is, Ketonal changes chronoinotropic relationship of the contractile activity of the colon in cases of stomach and jejunum.

Chronic introduction of celebrex increases the frequency of slow waves EMA from 17.6 to 23.8 in amplitude from 0.20 to 0.49 (143%). Thus, celebrex enhances and speeds up slow-wave electromotive AK�Yunosti, enhancing motor skills jejunal ulcers of the stomach and the jejunum.

Morphological study of gastric ulcers has shown that the edge of the ulcer saped, the bottom is filled with detritus gray-yellow, gastric cancer cystic expanded; venous vessels sharply dilutionary, filled with blood. Morphological study of the ulcer jejunum showed that lint deformed and infiltrated lymphoid cells, blood vessels dilated.

Morphological study of pancreatic cancer revealed swelling of the slices, increase midorikawa and intralobular connective tissue. Thin intralobular connective tissue layer is shared by a small group of cells. In the interlobular space are dilated veins with the regional standing of red blood cells. The density of endocrinocytes in the islets reduced: detected extended intervals between the cells is filled with connective tissue with a single capillaries. Found small clusters of damaged cells. Marked degeneration of the islets of Langerhans. In pancreatic duct detected the accumulation of proteinaceous secret, which hinders its outflow into the duodenum and creating conditions for the development of pancreatitis.

Morphological study of ulcers of the stomach and the jejunum and pancreas in comparable terms in the conditions of advanced�to accept the introduction of non-steroidal anti-inflammatory drugs showed they have a gastroprotective effect by improving the functioning of the gastric glands, restoration of blood supply to the affected area, which contributes to more rapid epithelialization of the ulcer. Antireproductive the effect of chronic administration of NSAIDs is more pronounced development of scar tissue and epithelialization of the ulcer, the restoration of brunerovy glands, as well as in the normalization of the diameter of the vessels of the submucosa and muscular layer, which leads to an increase in electric activity of the jejunum with the chronic administration of nonsteroidal anti-inflammatory drugs. Normalized passage protein of secretion by pancreatic duct, resolving blood stasis, improve the functional state of Exo - and endocrinocytes.

Entero - and pancreatoblastoma action is determined by the activation electromotor activity of the pancreatic duct: the frequency of the slow waves is increased from 12.5 min (25%), the amplitude is increased from 1.0 to 1.5 mV (50%).

Sources of information

1. Burian M, Geisslinger G. Clinical pharmacology of the selective COX-2 inhibitors. Orthopade. 2003, Dec; 32(12):1078-87.

2. Karadas B. et al. Additive interaction of intraperitoneal dexmedetomidine and topical nimesulide, celecoxib and DFU for antinociception. Eur J Pharmacol. 2007, Feb, 5; 556(1-3):62-8.

Method entero - and pancreatoblastoma action Nestea� - breaking anti-inflammatory drugs in the simulation of gastric ulcer and/or duodenal ulcer, and/or pancreatitis, namely that prior to modeling courses of introduction of salts of celebrex or ketone, wherein the drugs are administered parenterally, and during the first three days of the course at a dose of 2.5-3.1 mg/kg, followed by an introduction in the course of three days at the dose of 1.5-2.4 mg/kg, during the next four days at a dose of 0.5-1.4 mg/kg, followed by a repetition of the course in 1.5-2 months, and the first three days of a repeated course dose of 0.7-2.0 mg/kg, the following three days, the dose is 2.1-2.6 mg/kg, the final four days dose of 2.7-3.1 mg/kg.



 

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6 ex

FIELD: medicine.

SUBSTANCE: present invention refers to compounds having formula III such as below, wherein: Q represents C(Y3) or N; R represents H, -R1, -R1-R2-R3, -R1-R3 or -R2-R3; R1 represents heteroaryl or heterocyclyl each of which is optionally substituted by one or more C1-6alkyls, hydroxyC1-6alkyls, oxogroups or halogenC1-6alkyls; R2 represents -C(=O), -O, -C(R2')2, -C(R2')2C(=O), -C(R2')2C(=O)NR2', C(R2')2 N(R2')C(=O), -C(=NH), -C(R2')2NR2' or -S(=O)2; each R2' independently represents H or C1-6alkyl; R3 represents H or R4; R4 represents C1-6alkyl, C1-6alkoxygroup, aminogroup, C1-6alkylaminogroup, di(C1-6alkyl)aminogroup, heterocyclyl, C1-10alkylheterocycloalkyl, heterocycloalkylC1-10alkyl each of which is optionally substituted by one or more C1-6alkyls, C1-6alkylaminogroups, di(C1-6alkyl)aminogroups, hydroxygroups, hydroxyC1-6alkyls, C1-6alkoxygroups, oxogroups or halogenC1-6alkyls; X represents CH; X' represents CH; and the rest symbols have values as specified in the patent claim. The compounds of formula III inhibit Bruton's tyrosine kinase (Btk). There are also described compositions containing the compounds of formula III, and at least one carrier, thinner or excipient, and a method for producing the compound of formula X in accordance with the following procedure.

EFFECT: compositions are effective for modulating Btk activity and treating diseases related to Btk hyperactivity, and can be used for treating inflammatory and autoimmune diseases related to disturbed B-cell proliferation, such as rheumatoid arthritis.

22 cl, 2 tbl, 260 ex

FIELD: medicine.

SUBSTANCE: method for preparing an agent possessing anti-inflammatory, diuretic and antioxidant activity, involving milling Spiraea salicifolia shoots representing a mixture of leaves, blossom and shoots, extracting them three times by gradual maceration, mixing in infusing, filtering, condensing, separating, drying in the certain environment.

EFFECT: agent shoes the pronounced anti-inflammatory, diuretic and antioxidant activity.

2 dwg, 12 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and represents a controlled-release preparative form of diacerein administered once a day for treating or autoimmune diseases or their complications. The preparative form contains a core, an active layer, a sustained-release film layer and a delayed-release film layer, wherein the active layer is followed by the sustained-release film, and the delayed-release film layer thereafter. The sustained-release film layer contains ethyl cellulose polymer, povidone, triethylacetate and talc; the delayed-release film layer contains Eudragit polymer, triethylacetate and talc.

EFFECT: reducing the negative side action of diacerein.

18 cl, 23 ex, 33 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to microbiology, namely to using bacteria, and describes a composition containing microorganisms, a method for preparing probiotics with the anti-inflammatory action and a method for preparing an anti-inflammatory composition containing the probiotics. The composition according to the invention is characterised by the microorganism count subject to the short-time high-temperature processing at 120-140°C for 5-15 seconds.

EFFECT: invention can be used for preparing the compositions for treating or preventing the inflammatory disorders for the probiotics for dairy products.

10 cl, 7 dwg

Antiviral compounds // 2541571

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula I, such as below, or its pharmaceutically acceptable salts. What is described is a method for preparing them.

,

wherein: A independently from B means phenyl,

, or ,

and B independently from A means phenyl,

, or ,

and the values Z, Y, D, L1, L2, L3, Z1, Z2 are presented in the patent claim.

EFFECT: compounds are effective for hepatitis C virus (HCV) replication inhibition.

17 cl, 3 tbl, 8 dwg, 177 ex

FIELD: medicine.

SUBSTANCE: group concerns using undecapeptide - H-Tyr-Pro-D-Arg-D-Arg-D-Arg-D-Arg-D-Arg-D-Arg-D-Arg-D-Arg-Gly-OH·9HCl as an analgesic agent. The group of inventions also concerns a dosage form containing the above peptide as an active substance for treating acute and chronic pain syndromes.

EFFECT: stable and prolonged analgesic effect both in the enteral, and oral route of administration.

3 cl, 2 ex, 2 dwg, 5 tbl

FIELD: medicine.

SUBSTANCE: group of inventions refers to veterinary science. A method for preparing a herbal therapeutic preparation for treating gastrointestinal diseases in young animals is characterised by the fact that 150-200 g of ground elm bark is placed into a thermally stable flask filled with 500 ml of distilled water, extracted for 3 days in the cold environment; the flask is then placed on a gas or electric stove, connected through a laboratory fridge to a cold water source; distillation of a liquid fraction is followed by sublimation of a solid fraction for 6-8 hours until the particles are carbonised completely; the preparation is collected in a sterile laboratory flask, and then agitated. A method of using the therapeutic preparation produced as described above is characterised by the fact that the preparation is administered into young animals of various species in a dose of 3-25 ml intraperitoneally once a day; in some cases, the preparation is administered again 48-72 hours later. The invention provides the fast and effective action of the preparation ensured by chemical composition and applicability of the preparation by intraperitoneal route of administration; ensuring the fast effect of the pathological process specific for the gastrointestinal tract.

EFFECT: preparation provides anti-inflammatory action on the involved gastrointestinal mucous membranes, relieves the inflammatory process considerably, and thereby reduces the receptor irritation that leads to normalising intestinal peristalsis and reducing diarrhoea.

2 cl, 2 tbl

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