Phospholipid nanoform for oral application (sachet) and method for preparing it (versions)

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, pharmacology and concerns an oral granulated dosage form in sachets containing phospholipids in the form of particles of small (20-30 nm) diameter, glycyrrhizic acid and its salt (including sodium glycerrhizinate), as well as carbohydrate (including maltose) and excipients (granulation, anti-clotting and powder), as well as to a method for preparing it by mixing fat and water phases of herbal phospholipids and acceptable carbohydrate to prepare an emulsion, cooling to 50°C and passing through a microfluidiser for 4-5 cycles under pressure 2000 atm.

EFFECT: preparation shows high activity.

6 cl, 1 tbl, 5 ex

 

The technical field to which the invention relates.

The invention relates to the field of medicine, pharmacology, and relates to oral granular pharmaceutical preparation in the form of "sachet"containing phospholipid particles are small (20-30 nm) diameter, glycyrrhizinic acid and its salts (including sodium glycyrrhizinate), and carbohydrates (including maltose) and excipients (promotes granulation, prevent caking and intended for dusting). The drug is intended for the prevention and treatment of liver diseases after intoxication, inflammations, viral or toxic origin. A special case of receiving phospholipid particles of the specified range is microfluidizer.

The level of technology

Known composition and method for producing single-layer lamellar liposomal suspensions containing phospholipids (U.S. Patent No. 20100086573). As one of the ways to obtain a single-layer liposomes declared microfluidizer. In contrast to the claimed method involves obtaining liposomes in the range 50-290 nm, obtaining fat-soluble and water-soluble phase at a ratio of parts 5-33% and 67-95%, respectively.

In patent No. 20080286353 discussed the method of obtaining cationic liposomes containing phospholipids, to deliver immunogenic material as the e vaccines with the use of microfluidizer. However, the sodium glycyrrhizinate not claimed as an active connection.

Also known is a method of obtaining liposomes containing phospholipids, with the use of microfluidizer (U.S. Patent 20040247660). The method involves obtaining liposomes loaded with biologically active compounds and stable protein. The sodium glycyrrhizinate not claimed as an active connection.

Closest to the claimed invention is a phospholipid drug and its shape is described in EN 2373924 (prototype). The patent relates to relates to oral dosage forms of phospholipid drug for the prevention and treatment of liver diseases, disorders of lipid metabolism and recovery of liver function after intoxication in the form of nanoparticles with a diameter of 30-50 nm. However, the nanoform of the drug is enclosed in capsules, has several disadvantages. So, to achieve a biological effect from taking phospholipids requires a relatively large dosage. This requires large quantities of capsules.

Thus, despite the fact that some ways of getting oral liposomal forms containing phospholipids and salts of glycyrrhizic acid known from the prior art, the method of obtaining phospholipid nanoparticles, consisting of phospholipids, maltose and sodium glycyrrhizinate, in the form of the e Sasha proposed by the authors for the first time.

Disclosure of inventions

Inventive task is solved in that the proposed nanoform fosfolipidnogo granulated drug "Phosphogliv" in the form of sachets containing particles of small size. The technical result consists in obtaining a stable and convenient for oral administration of nanoform of the drug on the basis of vegetable phospholipids, which are characterized by the same small size. A particular case of the solution of this problem is the use of microfluidizer, which allows to obtain particles in one nanometer range (20-30 nm), prisoners in granules of high strength, excluding sintering, sliianie during storage, with good flowability. As auxiliary components, prevent caking, can be used components selected from the group (not limiting of the scope of claims of the invention): calcium carbonate, calcium hydrogen carbonate, ortho-calcium phosphate 1-substituted, ortho-calcium phosphate 2-substituted, ortho-calcium phosphate 3-substituted, ortho-phosphate magnesium 1-substituted, ortho-phosphate magnesium 2-substituted, ortho-phosphate magnesium 3-substituted, isopropylidene mixture, mannitol, microcrystalline cellulose, cellulose powder, fatty acids, salts of aluminum, calcium, sodium, magnesium, potassium and ammonium, sodium carbonate, sodium bicarbonate, CME is ü carbonate and sodium bicarbonate, magnesium carbonate, magnesium bicarbonate, magnesium oxide, sodium ferrocyanide, potassium ferrocyanide, ferrocyanide calcium phosphate bone, sodium silicate, meta-silicate of sodium, silicon dioxide, amorphous calcium silicate, magnesium silicate, magnesium trisilicate, talc, sodium aluminosilicate, potassium aluminosilicate, calcium aluminosilicate, bentonite, aluminum silicate, potassium silicate, polydimethylsiloxane, isomalt, isomaltol.

As auxiliary components, promotes granulation, can be used by components that are not restrictive of the scope of claims of the invention and selected from the group of natural gum, acacia or tragakant, gelatin, sugar (in the form of syrup concentration 50-67%), starch paste, cellulose derivatives, alginic acid and alginates.

As auxiliary components, contributing to the slide and used for dusting, can be used components selected from the group (not limiting of the scope of claims of the invention): paraffin, cocoa butter, hydrogenated vegetable oils, stearates of calcium and magnesium, pure stearic acid, talc, starch, tween-80.

The implementation of the invention

Interest in liposomes as delivery systems, there is from 1965, when it was determined a wide range of biological, pharmaceutical, and industrial applications. JV is the ability of liposomes to encapsulate and thus, to distinguish hydrophilic biologically active compounds predetermined their use in biological systems, including for the delivery of genes, drugs and other biologically active compounds, as well as phase-contrast agents for diagnostic purposes.

The greatest practical interest liposomes cause all the same as the transport system of drug delivery in vivo, as has long been known, they have a relative selectivity, which contributes to a relatively high accumulation of the drug in the delivery location.

Liposomes have several advantages compared to other nanotransport systems. First, liposomes composed of lipid (phospholipid) layer, which is akin to the cellular composition of biological membranes. Such natural biocompatibility allows them to easily penetrate into the cell. Secondly, as carriers of biologically active compounds, liposomes have many advantages for the reduction of side effects from medication, which distinguishes liposomal drugs from their native counterparts.

One of the problems to overcome are directed technology development effort is to provide undoubted targetnode delivery of liposomal drugs. A variety of sizes, modificat the second surface of liposomes, including with the aim of increasing their bioavailability, has accumulated extensive experience in understanding what needs to be aimed at the development of such delivery systems. Often increasing targetnode is achieved by conjugation of liposomal systems with a specific ligand with a receptor or other object to bind to. However, this approach makes a significant increase in the cost of the product and may reduce the biological activity of the product during storage and other provocative factors (temperature, pH etc). Therefore, most efforts aimed at creating transport of liposomal systems with guaranteed size, since this option, albeit less specific, but still affects targethost drug delivery. Critical and very important parameter is the homogeneity of the particle size. It is easier to control the dosage of drugs, and the rate of excretion of the drug.

Taking into account the latest technological methods to obtain liposomes with sizes fairly wide range. The most frequently used (rather, out) liposomes ranging in size from 200-400 nm. However, these liposomes are often captured by macrophages and organs of the reticulo-endothelial system, so part of liposomes is filtered by the body itself, not opada in target cells. Such losses can be controlled, if the use of liposomes of smaller diameter. One of the advantages of the small size of liposomes is the fact that liposomes of small (less than 200 nm diameter show a lower rate of clearance than liposomes large size (Ishida et al. 2002; Litzinger et al. 1994). This allows the liposomes to stay in the bloodstream longer, which increases the probability of target hit in right compartment of the body.

There are many different methods for the development and creation of liposomal transport systems. Among them are well-known ultra-fine spray, crystalline or amorphous deposition, grinding ball mill, high pressure homogenization, microfluidizer etc. From the point of view of physico-chemical properties of the product, as well as related biological properties of these technologies give the possibility of obtaining the most diverse range of nanoparticles with different properties, stability, size, specifics of transport in the cells of the body.

One of the most suitable technologies for small liposomes is microfluidizer (Jahn et al., 2008). In the process of working on microfluidizer product flow is strongly accelerated, creating inside the flow shear rate, which is higher than the normal value. All then who their product is subjected to the same conditions: constant pressure gives the output particles, homogeneous in size; high pressure and high speed allow to take out particles of small size. Moreover, a very large pressure range (up to 40000 psi) opens the possibility of applying microfluidizer for different applications and materials, in obtaining small in size and homogeneous distribution of particles not containing impurities by-products.

Thus, the main advantages of microfluidizer are:

- Ability to obtain smaller particles (20-30 nm);

- Reduction of production cycles to obtain the required particle size;

- Obtained particles have a more narrow size distribution;

- The process takes much less time;

- More accurate control of the applied force;

- Higher level of the pressure applied (up to 40000 psi or 2600 ATM);

- The opportunity to work with a small amount of sample, and continuously flowing the product;

- Minimal pollution;

- Obtain a homogeneous and stable dispersions and emulsions;

- Obtaining a large number of lipid particles without dissolving phospholipids in organic solvents;

- Ability to reduce cholesterol.

The size of the particles, including lipid, which can be obtained using microfluidizer allows you to enter the x intravenously without fear of clogging of small blood vessels. This technology allows the process under aseptic conditions. Reproducibility upon receipt of the particles makes it possible to have standards for comparison in the modification of parameters in studies of various kinds.

Technological advantages thus obtained product is a guarantee of its reproducibility. With regard to biological advantages, the thus obtained particles are endowed with completely new properties. On the one hand, to minimize the size of the particles medicines almost always leads to an increase in surface area and, consequently, to increase therapeutic efficacy of the product. Often this is achieved by increasing the bioavailability of the active substance. On the other hand, this option minimize particles is of particular interest from the point of view of delivery of the substances thus obtained particles provide the relative targeting of Leksredstva in organs and tissues.

Thus obtained particles it is necessary to create favorable conditions for their storage, and the patients to enable convenient dispensing. One option is a pharmaceutical form of "sachet". The use of the drug in the form of Sasha saves the consumer (patient) from repeated use malodonilovsky forms (such as, for example, capsules) the day and allows you to take all the necessary daily dose in a convenient, "dose" version. Secondly, the capsule version of phospholipid drug over time leads to caking of the active ingredients and, consequently, creates a precedent for increasing the reactivity of substances that are in close proximity to each other. This will, in particular, to accelerate the oxidation of phospholipids, to the destruction and the sticking of sediment, reduction of shelf life and, therefore, weakening or loss of the claimed biological activity of the drug. Often the addition of auxiliary substances simply provides a solution only technological problems associated with the process of filling capsules (and/or flowability fill mix), but does not affect the stability and shelf life of the finished product. A process such as granulation, necessary for placing the medicinal substance in the sachet, substantially prevents caking of the active ingredients.

Another advantage of the sachet dosage forms capsule before nanoparticle option is the cheaper production costs of packaging the same volume of product. For example, the cost of one capsule maximum size (up to 1.5 grams of dry matter) is 0.4 rubles, while the cost of one sachet containing 10 grams of the same product, for example the t 0.35 RUB It is easy to calculate that, given the ceteris paribus (the cost of raw materials, the same requirements for the cleanliness of premises, similar power and equipment costs, etc.) production costs of product packaging in sachets will be 8-9 times cheaper. In addition, there is no need to blisterine I pack Sasha creates conditions for product storage, the ingress of light and moisture.

It follows that Sasha is an option for nanoform phospholipid drug containing particles of small size, has certain physicochemical, biopharmaceutical, and economic benefits. Summarizing the above, we can conclude that the combination of small nanoform phospholipid granulated drug "Phosphogliv" drug in the form of sachets optimally solves the problem of preservation of the pharmaceutical properties of the product, convenient and optimal daily dosing, delivery to the target organ (liver), and saves production costs.

The invention is illustrated by the following examples.

Example 1. Obtaining water and fat phase to the emulsion 13 g trinational salts of glycyrrhizic acid and 25 g of Lipoid S100, cut into thin slices, was dissolved in 250 ml of water for injection (pH of 6.7). Stirred using a mechanical prevented the u, and thus, the solution A.

Dissolved of 87.5 g of maltose in water for injections, carefully mixing in the mixer, slightly heated until complete dissolution (until the solution is clear), the final volume was brought to 250 ml, and thus, the solution B.

Both solution a and B were mixed. Brought the total volume to 500 ml with water for injection and thoroughly mixed on a mixer to obtain a homogeneous emulsion.

Example 2. Getting phospholipid emulsion on microfluidizer.

To obtain a phospholipid emulsion used microfluidizer MEN, Microfluidics, USA. Oflouisiana emulsion was collected in the collection, where shimmered in cumulative capacity of fluidizer for further fluidization. The temperature of the emulsion was maintained at a constant level and does not exceed 50°C. the Cooled emulsion was carried out by existing in this unit cooling system.

The emulsion was passed through fluidizer from 1 to 5 cycles under a pressure of 2000 ATM. After each cycle of fluidization samples were taken for measurement of light transmission (the measurements were carried out either on the spectrophotometer Ajilent 8453 UV-visible (Germany), using HP UV-Visible ChemStation, either on the device Spectroman 410, Hungary with a filter at 660 nm) and the size of the obtained particles measured using the photon correlate the frame spectrometer (Beckman-Coulter N5 software PCS Control Software Version 3.02 (Copyright Beckman Coulter, 2003). The data obtained are given in Table. 1.

Example 3. Obtaining granulated nanoparticle-based drug phospholipids.

Homogeneous emulsion obtained in example 2, must have the following characteristics:

- transparent, slightly opalescent liquid;

the transmittance of the sample at 660 nm relative to water of not less than 60%.

The resulting emulsion was poured into the tray stainless steel with thickness of 1.5-2.0 cm and placed on a shelf lyophilic drying. The product was frozen at -40°C, then the regiment was heated to a temperature of +10°C. the Frozen sample was subjected to freeze-drying (LSL SECFROID, LYOLAB F, Germany) for 48 hours.

Example 4. An example of the formulation of the finished mixture is granulated nanoparticle-based drug phospholipids.

Obtained in example 3 dried mass was unloaded from the tray, crushed and subjected to dry granulation on the grid with a diameter of 1.2 mm, the Obtained granulate outrival 4,06 g microcrystalline cellulose, 1.92 g of calcium carbonate, 0,02 talc and 0.006 g of calcium stearate is not more than 8-10 minutes to a state of fine-grained loose weight and packaged in 2.5 g in plastic containers or packaging type "Sasha".

Example 5. Comparison of susceptibility to moisture absorption and caking nanoparticle drug in the sachet and capsule.

In the dry Cup was placed 10 g is mm (10±0.01 g) of the analyzed granulated drug closed the lid and weighed. Then the Cup with the sample (without cover) was placed in a desiccator (desiccator contained a saturated solution of ammonium chloride, which allowed to maintain in a desiccator humidity 80%). The Cup with the investigational drug was kept in a desiccator for one day at room temperature +22°C. Then the Cup is weighed together with the cover. The procedure was performed three times. The same procedure was done with a capsulated version of the reference product "Phosphogliv". After completion of procedures assessed the propensity of the sample to moisture absorption according to the following formula:

B=(M1-M2)/M×100,

where M is the original mass of sample in grams;

M1- weight of sample the sample after the moisture in grams;

M2- the mass of the Cup with the sample to moisture in grams.

The end result was the average of the results of three parallel measurements. In the calculations it is obtained that the average propensity to moisture absorption of the capsule of the drug "Phosphogliv amounted to 2.1%, while the same parameter granulated drug "Phosphogliv" - 1.3%. Although both drugs showed relatively good moisture resistance, granulated option is the most resistant to high humidity, primarily due to the optimum composition of the auxiliary materials is lnyh components.

Next cups with weight (without lids) were placed in a drying oven and dried. Then the dried powders were poured from a height of 1 meter on a sieve with the appropriate cell size, pre-selected under the original dimensions of the capsule and granular variant of the compared drugs. The powder was sifted. Lumps that do not pass through the sieve were weighed. The percentage of lumps in each of the preparations was characteristic tendency to caking (in %), which was calculated by the formula:

C=MK/M×100,

where MK is the mass of the formed lumps, not passed through the sieve, in grams.

On average received that for drug Phosphogliv", placed in capsules, amounted to 1.1%, and for granulated drug Sasha - 0.3%. This experiment proves that optimally balanced composition of auxiliary components of the dosage form of the drug in the sachet prevents caking during storage.

Table 1
Resizing phospholipid nanoparticles from cycles fluidization.
No. of cycleParticle size, nmThe transmittance, % at 660 nm
1 1678,9132,13
2867,2440,24
3378,4549,12
457,6157,18
527,2166,35

BIBLIOGRAPHIC DATA

- Patent USA 20100086573. COMPOSITION AND METHOD FOR PREPARING STABLE UNILAMELLAR LIPOSOMAL SUSPENSION.

- Patent USA 20080286353. CATIONIC LIPOSOMES CONTAINING IMMUNE RESPONSE GENERATING MOIETIES.

- Singh CU. Protein-stabilized liposomal formulations of pharmaceutical agents. Patent USA 20040247660.

Jahn, A., Reiner J.E., N. W. Vreeland, D.L. DeVoe, Locascio LE, Gaitan M. Preparation of nanoparticles by continuous-flow microfluidics. J. Nanopart Res 2008.

- Ishida, T., Harashima H., Kiwada H. (2002) Liposome clearance. Biosci Rep 22(2): 197-224.

- Litzinger, D.C. et al. (1994) Effect of liposome size on the circulation time and intraorgan distribution of amphipathic poly(ethylene glycol)-containing liposomes. Biochim Biophys Acta Biomembr 1190(1): 99-107.

Jahn A. et al. (2007) Microfluidic directed formation of liposomes of controlled size. Langmuir 23(11): 6289-6293.

Jahn A. et al. (2004) Controlled vesicle self-assembly in microfluidic channels with hydrodynamic focusing. J Am Chem Soc 126(9): 2674-2675.

1. Oral drug phospholipid preparation for prophylaxis and treatment of diseases of the liver, which contains phospholipids of vegetable origin in the form of small particles (20-30 nm) diameter, glycyrrhizinic acid and its salts (including glycyrrhizinate on the model), as well as carbohydrates (including maltose) and auxiliary components, characterized in that the dosage form granular, and presented in the form of "sachet".

2. Oral drug phospholipid preparation according to claim 1, containing a carbohydrate selected from the group of lactose, maltose, isomaltose, arabinose.

3. Oral drug phospholipid preparation according to claim 1, containing auxiliary components, prevents caking and selected from the group of: calcium carbonate, calcium hydrogen carbonate, ortho-calcium phosphate 1-substituted, ortho-calcium phosphate 2-substituted, ortho-calcium phosphate 3-substituted, ortho-phosphate magnesium 1-substituted, ortho-phosphate magnesium 2-substituted, ortho-phosphate magnesium 3-substituted, isopropylidene mixture, mannitol, microcrystalline cellulose, cellulose powder, fatty acids, salts of aluminum, calcium, sodium, magnesium, potassium, and ammonium, sodium carbonate, sodium bicarbonate, a mixture of carbonate and bicarbonate of sodium, magnesium carbonate, magnesium bicarbonate, magnesium oxide, sodium ferrocyanide, potassium ferrocyanide, ferrocyanide calcium phosphate bone, sodium silicate, meta-silicate of sodium, silicon dioxide, amorphous calcium silicate, magnesium silicate, magnesium trisilicate, talc, sodium aluminosilicate, potassium aluminosilicate, calcium aluminosilicate, bentonite, aluminum silicate, potassium silicate, polydimethyl is Xan, isomalt, isomaltol.

4. Oral drug phospholipid preparation according to claim 1, containing auxiliary components, promoting granulation, selected from the group of natural gum, acacia or tragakant, gelatin, sugar, starch paste, cellulose derivatives, alginic acid and alginates.

5. Oral drug phospholipid preparation according to claim 1, containing auxiliary components that contribute to slip and for dusting, selected from the group of paraffin, cocoa butter, hydrogenated vegetable oils, stearates of calcium and magnesium, pure stearic acid, talc, starch, tween-80.

6. The method of obtaining oral phospholipid drug of the drug according to claim 1, characterized by the fact that they get fat and aqueous phase on the basis of vegetable phospholipids and acceptable carbohydrate obtained phase mixed to obtain an emulsion is subjected to cooling to 50°C, followed by transmission through microfluidizer for 4-5 cycles under a pressure of 2000 ATM.



 

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12 cl, 5 ex

FIELD: medicine.

SUBSTANCE: liver is resected in an animal experimentally. A pharmacological protection is presented by Mexicor and Serotonine Adipinate. On the operation day, 5% Mexicor is used in the form of intravenous slow stream introductions twice - 35 minutes before the operation in a dose of 5 mg/kg of weight and 11 hours after the first introduction in a dose of 7 mg/kg of weight. Serotonine Adipinate dissolved in 5 ml of isotonic solution NaCl is used in the form of intravenous slow stream introductions three times - 1 hour before the operation in a dose of 0.15 mg/kg of weight, 2 hours after the first introduction in a dose of 0.2 mg/kg of weight, 10 hours after the first introduction in a dose of 0.1 mg/kg of weight. During the postoperative period, Mexicor and Serotonine Adipinate are introduced for 8 days. Mexicor is introduced three times a day at 9 o'clock in a dose of 2.5 mg/kg of weight, at 15 o'clock in a dose of 1.5 mg/kg of weight, at 21 o'clock in a dose of 6 mg/kg of weight. Serotonine Adipinate is introduced twice a day - at 8 o'clock in a dose of 0.15 mg/kg of weight, at 17 o'clock in a dose of 0.1 mg/kg of weight.

EFFECT: method provides prolonging a period of safe hepatic exsanguination, ensures treating and preventing ischemic and reperfusion injuries of hepatic tissues and microcirculatory bloodstream, promotes preventing major bleedings accompanying hepatic operations.

3 ex, 3 tbl, 3 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new benzimidazole derivatives of general formula (I) or to its pharmacologically acceptable salts wherein R1 represents a C6-aryl group which can be substituted by 1-3 groups optionally specified in a group of substitutes (a), or a heterocyclic group which represents pyridyl, dihydrobenzofuranyl, 1,3-benzodioxolyl, tetrahydropyranyl, tetrahydrofuranyl which can be substituted by 1-3 groups optionally specified in a group of substitutes (a), R2 represents a C1-C6 alkyl group, R3 represents a C6-aryl group which can be substituted by 1-2 groups optionally specified in a group of substitutes (a), Q represents a group represented by formula =CH-, or a nitrogen atom and a group of substitutes (a) represents a group consisting of a halogen atom, a C1-C6 alkyl group, a C1-C6 halogenated alkyl group, a carboxyl group, a C2-C7 alkylcarbonyl group, a C2-C7 alkoxycarbonyl group, a C1-C6 alkoxy group, a C1-C6 halogenated alkoxy group, an amino group, a 4-morpholinyl group and a di-C1-C6 alkyl)amino group. Also, the invention refers to a pharmaceutical composition based on a compound of formula (I), to a PPARγ activator/modulator based on the compound of formula (I), to using the compound of formula (I), to a method of reducing blood glucose, to a method of activating PPARγ, a method of treating and/or preventing said pathological conditions.

EFFECT: there are produced new benzimidazole derivatives showing PPARγ modulatory activity.

41 cl, 2 dwg, 6 tbl, 76 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed is means for prevention (prophylaxis) of liver injury in formation of syndrome of combined dystrophic-degenerative changes of mesenchimal derivatives in case of local chronic inflammatory process, located outside the liver (CDDCMD in case of LCIP located outside the liver), which represents hormone of pineal gland - melatonin and corresponding method of prevention (prophylaxis) of liver injury in formation of CDDCMD in case of LCIP.

EFFECT: invention ensures reduction of microcirculatory disorders; prevention of dystrophic changes of parenchymal cells, proliferation of connective tissue, change of structure of walls of hepatic veins vessels; prevention of increase of quantity of mast cells in surrounding of portal tract vessels; malantonin toxicity being low and side effects - minimal.

2 cl, 6 dwg, 2 tbl

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to physiotherapy, gastroenterology. Method includes introduction of diet No5, internal intake of mineral water with the following carrying out transverse galvanisation of epigastrium area, general coniferous baths and impact with physical factor. As physical factor used is electromagnetic radiation of extremely high frequency (EHF). Impact is performed by broad-band noise emitter with frequency 40-63 GHz. Impact is performed on 3 and 4 projection zones in area of the right hypochondrium and on the area of sternum. Impact is performed daily, 10 minutes on each zone. Course includes 10-12 procedures.

EFFECT: method improves physical-chemical properties of bile, contributes to bile secretion due to normalising action on motor and secretory function of gastrointestinal tract, improves blood circulation and liver regeneration, increases non-specific resistance and adaptive possibilities of organism, normalises psycho-emotional status.

2 ex, 2 tbl, 1 dwg

FIELD: medicine.

SUBSTANCE: under the conditions of modelling cirrhosis in experiment, the preparation EMBRYOBLASTE is introduced in liver tissue by means of an injector needle at the depth up to 0.1 cm. The preparation is introduced along a front surface of the liver, 2 injections in each lobe of the liver to form a papula. The volume of one injection makes 0.3 ml.

EFFECT: reduced fibrotic regeneration of liver tissue by means of intensifying liver cell proliferation and extracellular matrix resorption with reducing a degree of manifestation of venular and periportal fibrosis, reducing haemo- and lymphostasis, regenerating capillarisation of liver sinusoids without affecting cell architectonics of the organs.

4 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and pharmaceutics, and concerns a storage-stable composition in the form of nanoparticles of size 10-20 nm containing a fatty acid salt, phosphatidyl choline and maltose for the integration of biologically active substances, particularly, drugs, as well as drug compositions containing the fatty acid salt, phosphatidyl choline, maltose and a drug substance, and a method for preparing them.

EFFECT: development of the storage-stable composition.

4 cl, 5 tbl, 5 ex

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