Therapeutic agent for endothelial dysfunction correction

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, namely to cardiology, and concerns the endothelial dysfunction correction. That is ensured by a therapeutic agent containing an activated potentiating form of vascular endothelium growth factor (VEGF) antibodies. The activity of the therapeutic agent is related to the process of multiple serial dilutions in an aqueous or aqueous-alcohol solution in a combination with an external mechanical vertical agitation of each dilution.

EFFECT: method provides the effective L-NAME-induced endothelial dysfunction correction in experiment.

6 cl, 1 ex, 1 tbl

 

The invention relates to medicine, in particular cardiovascolari, and can be used for the correction of endothelial dysfunction.

The prior art method of correction of endothelial dysfunction with a mixture of solutions of homeopathic dilution of polyclonal antibodies to endothelial synthase nitric oxide person (EN 2306953 C1, A61K 39/395, 2007). However, the disadvantage of this invention is that the use of a mixture of solutions of homeopathic dilution of polyclonal antibodies to the NO-synthase effectively with endothelial dysfunction associated with low levels of endothelial NO-synthase, and may not provide therapeutic efficacy in endothelial dysfunction with normal production of NO-synthase.

The invention is aimed at creating an effective and safe drug for the correction of endothelial dysfunction in preventing inflammation of the vessel wall and the development of endothelial dysfunction.

The solution of this problem is provided by the fact that the drugs are for the correction of endothelial dysfunction contains activated - potentiated form of antibodies to factor a vascular endothelial growth (VEGF).

Claimed, the drug can be used for the correction of L-Name-induced endothelial, disfunkcii rats male Wistar, caused by daily intraperitoneal injection of 2 times per day L-Name at a dose of 12.5 mg/kg 4.5 mg/kg (9 ml/kg/day), by intragastric introduction of the activated - potentiated form of antibodies to the growth factor of vascular endothelium in the form of a mixture of solutions of homeopathic dilution C12, C30, C200.

Activated - potentiated form of antibodies to factor a vascular endothelial growth can be used in the form of activated - potentiated aqueous or aqueous-alcoholic solution, the activity of which is due to the process of multiple serial dilutions in water or water-alcohol solvent in combination with an external mechanical impact - vertical shaking of every dilution.

In addition, the drug can be made in a solid dosage form that contains an effective amount of granules neutral media saturated with a mixture of activated - potentiated form of antibodies to the growth factor, vascular endothelium, and pharmaceutically acceptable additives, which include lactose, cellulose microcrystalline and magnesium stearate.

In addition, water or water-alcohol solution of the activated - potentiated form of antibodies to factor a vascular endothelial growth can be obtained by repeated consecutive dilution in the op is Tania's story with an external mechanical impact - vertical shaking of every dilution of the matrix solution of antibodies to factor a vascular endothelial growth with a concentration of 0.5÷5.0 mg/ml

In addition, the activated - potentiated form of antibodies to factor a vascular endothelial growth can be used in the form of mixtures of different breeding, prepared according to homeopathic technology, mainly in the form of a mixture of the three solutions were prepared from a matrix solution, diluted, respectively, in the 10012, 10030and the 100200once that is equivalent to boast of dilutions C12, C30, C200, prepared according to homeopathic technology.

Proposed an activated - potentiated form of antibodies to the growth factor of vascular endothelium in medicine (i.e. the form of antibodies, prepared according to homeopathic technology exponentiation by repeated consecutive dilution in combination with external mechanical impact - vertical shaking of every dilution (see, for example, C. Schwabe "Homeopathic medicinal product", M, 1967, p.14-29), which has activity in pharmacological models and/or clinical correction of endothelial dysfunction)provides the activation of eNOS, increased neovascularization of ischemic tissues, resulting normalized vascular tone and kr is voobrajenie, increases tolerance to physical activity improves overall health.

Obtained in accordance with the invention, the drug represents a new pharmacological agent, which is characterized by the presence of specific pharmacological activity, no side effects, habituation and addiction, environmentally friendly and low cost.

In addition, the claimed medicinal product expands the Arsenal of drugs intended for the correction of endothelial dysfunction.

The drug is prepared as follows. For making an activated - potentiated form of antibodies using monoclonal or polyclonal antibodies, which can be obtained by known technologies - techniques are described, for example, in the book: Immunological methods, edited by G. of Primes, M, "Medicine", 1987, p.9-33; or, for example, article Laffly E., R. Sodoyer Hum. Antibodies. Monoclonal and recombinant antibodies, 30 years after. - 2005 - Vol.14. - N 1-2. P.33-55.

To obtain antibodies to factor a vascular endothelial growth as an immunogen (antigen) for immunization of rabbits can be used adjuvant and whole molecule growth factor vascular endothelial following sequence:

It is possible to generate antibodies to the growth factor of soudi is that endothelium using as immunogen (antigen) polypeptide fragment of a growth factor, a vascular endothelial selected, for example, of the following sequences:

Preferred for the preparation of the claimed medicinal product is the use of antibodies to the growth factor of vascular endothelium, which as a matrix (primary) solution with a concentration of 0.5÷5.0 mg/ml, is used for the subsequent preparation of the activated - potentiated form.

Polyclonal antibodies can be obtained by active immunization of animals. For this purpose a specially designed circuit animals make a series of injections required in accordance with the invention substances - antigens: growth factor vascular endothelium. As a result of this procedure is to obtain monospecific antisera with high content of antibodies that is used to produce the activated - potentiated forms. If necessary, conduct the purification of antibody present in anticigarette, for example, by the method of affinity chromatography, by application of salt fractionation by precipitation or ion exchange chromatography.

Before taking the blood sample for 7-9 days spend 1-3 intravenous injection for raising antibodies. In the process of immunization in rabbits take small blood samples to estimate the number of antibodies. The maximum level of immune response to wedenborn soluble antigens is achieved in 40-60 days after the first injection. After completion of the first cycle immunization of rabbits for 30 days to give to restore health and are reimmunization including 1-3 intravenous injection. To obtain antisera from immunized rabbits collect the blood in a centrifuge tube with a volume of 50 ml using a wooden spatula to remove from the walls of the tube formed clots and put the wand in the clot formed in the center of the tube. The blood is placed in a refrigerator (4°C) overnight. The next day remove the clot adhered to the spatula, and centrifuged remaining liquid at 13000g for 10 minutes the Supernatant (supernatant) is anticorodal. The resulting anticavity should be yellow. Add to anticigarette 20%, (weight concentration) NaN3to a final concentration of 0.02% and stored until use in a frozen state at -20°C (or without addition of NaN3- at -70°C). For selection of antisera antibody to factor a vascular endothelial growth produce absorption in the solid phase in the following sequence:

1. 10 ml of rabbit antisera diluted 2 times with 0.15 M NaCl type of 6.26 g of Na2SO4, mixed and incubated for 12-16 h at 4°C;

2. the precipitation is removed by centrifugation, dissolved in 10 ml of phosphate buffer and then dialysis is tons against the same buffer overnight at room temperature;

3. after removal of the precipitate by centrifugation, the solution was applied to the column with DEAE-cellulose, equilibrated with phosphate buffer;

4. the fraction of antibodies determined by measuring the optical density of the eluate at 280 nm.

Then make a clearance antibodies, for example, by the method of affinity chromatography obtained by attaching antibodies to the growth factor of vascular endothelium, which is insoluble matrix followed by elution with concentrated salt solutions.

Thus obtained buffer solution polyclonal antibodies to the growth factor vascular endothelium, with a concentration of 0.5÷5.0 mg/ml, preferably 2,0÷3,0 mg/ml is used as the matrix (primary) solution for the subsequent preparation of the activated - potentiated form of the drug.

Monoclonal antibodies can be obtained, for example, using hybridoma technology, which involves several steps: sequential immunization of animals, preferably mice, the allocation of the immunized animal an antibody-producing b-lymphocytes from lymphoid organs of the animal (spleen, lymph nodes); the creation of a hybrid (antibody-producing b-lymphocytes and hybridizing with myeloma cells); the cultivation of hybrid and selection of productive hybrid cells; screening reception is together with the antibodies hybridomas; cloning hybridoma cells; isolation of antibodies from the culture fluid and purification of monoclonal antibodies.

Mice make the immunization antigen - factor vascular endothelial growth mixed with adjuvant. After a few days in immunized mice produce lymphoid organs and prepare a suspension of cells. Choose the myeloma cells for hybridization with cells of immunized animals.

Cells of the immunized animal and myeloma cells are mixed and centrifuged. After centrifugation the supernatant was removed and to the precipitate add polyethylene glycol (0.5 ml 50%PEG solution) and incubated. Why were washed off the cells from the PEG. Next, cells with myeloma cells were placed in GAT environment and cultivated.

After cultivation was allocated surviving hybridoma cells with myeloma cells of the immunized animal, which retained the ability to synthesize and secrete antibodies.

Then spent the hybrid cloning and selection of the desired clones. Survivors GAT cells subcultured in a special plastic tablets, usually containing 96 wells with a capacity of about 0.2 cm3. To each well was put in an average of 10 hybridoma cells and cultured. After several days of cultivation, the content of each well was examined for the presence of antibodies needed specificnostima of holes, containing the desired antibodies are cloned, i.e. repeatedly subcultured on the same hole, but the rate of 1 cell per well, again, were cultured and tested for the presence of the desired antibodies. The procedure was repeated 1-2 times. Thus, selected clones producing antibodies only one of the desired specificity, i.e. monoclonal antibodies.

Then spent the selection of monoclonal antibodies from the culture fluid of hybridoma cells and carried out the purification of monoclonal antibodies using methods of chromatography, preferably affinity chromatography.

Thus obtained monoclonal antibodies to growth factor vascular endothelium, with a concentration of 0.5÷5.0 mg/ml, preferably 2,0÷3,0 mg/ml is used as the matrix (primary) solution for the subsequent preparation of the activated - potentiated form of the drug.

Preferred for the preparation of medicines is the use of a mixture of three water-alcohol dilution of initial matrix solution of antibodies, diluted, respectively, in the 10012, 10030and the 100200time, which corresponds to boast of dilutions C12, C30 and C200, prepared according to homeopathic technology. In carrying out the stated drugs in solid dosage form at a neutral novtel is applied to the mixture of these components.

The activated - potentiated form of antibodies to factor a vascular endothelial growth prepared by uniform reduction of the concentration in the serial dilutions 1 of the above matrix solution of 9 parts (for decimal dilution (D) or 99 parts (for centesimal dilution) or in 999 parts (for the thousandth breeding M) neutral solvent. with multiple vertical shaking ("dynamics") of each received cultivation and use separate containers for each subsequent breeding until you get the desired potency - ratio cultivation in homeopathic method (see, for example, C. Schwabe "Homeopathic medicinal product", M, 1967, p.14-29).

External processing in the process of reducing the concentration can be realized by ultrasound, electromagnetic or other physical effects.

For example, for the preparation of the 12th centesimal dilution C12 one part of the mentioned matrix solution of antibodies to factor a vascular endothelial growth with a concentration of 3.0 mg/ml diluted in 99 parts of a neutral aqueous or aqueous-alcoholic solvent and repeatedly (10 times or more) vertically shaken - potentiate received 1st somenoe C1 breeding. From the 1st centesimal C1 breeding prepare 2nd somenoe breeding C2. This operation surface is oraut 11 times, getting 12th somenoe breeding C12. Thus, 12th somenoe breeding C12 represents the solution obtained by diluting consistently in different tanks 12 times the 1st part of the initial matrix solution of antibodies to factor a vascular endothelial growth with a concentration of 3.0 mg/ml in 99 parts of a neutral solvent, a solution prepared by dilution of the matrix solution in the 10012time. Similar operations with a corresponding multiplicity of cultivation is performed to obtain a dilution C30 and C200.

When used as a biologically active liquid component of the mixture of various, mainly centesimal, the dilution of the active substance prepared according to homeopathic technology, each component of the composition (for example, C12, C30, C200) prepare separately for the above-described technology to their penultimate cultivation (respectively, to obtain C11, s, S) and then applied in accordance with the composition of the mixture in one container, one part of each component and mixed with the required amount of solvent (respectively, with 97 parts for centesimal dilution). You get the activated - potentiated form of antibodies to the growth factor of vascular endothelium in midget doses received by Sverrisdottir matrix solution, respectively, in the 10012, 10030and 100200RA is, equivalent mixture of centesimal dilution C12, C30 and C200, prepared according to homeopathic technology.

You can use the active substance in the form of a mixture of different breeding, for example, the decimal or centesimal, (D20, C30 C100 or C12, C30, with50 etc.), prepared according to homeopathic technology, the effectiveness of which is determined experimentally.

When potentiation instead of shaking in the process of reducing the concentration can also be external effects of ultrasound, electromagnetic or other physical effects.

Claimed, the drug can be used in solid dosage form that contains an effective amount of granules neutral media - lactose, saturated by soaking up the saturation a mixture of aqueous or aqueous-alcoholic solutions of the activated - potentiated form of antibodies to the growth factor, vascular endothelium, and pharmaceutically acceptable additives, including, primarily, lactose, cellulose microcrystalline and magnesium stearate.

For solid oral forms of the claimed medicinal product produced in the plant fluidized bed (for example, type "Huttlin Pilotlab" production company Hiittlin GmbH) irrigation until saturation of injected fluid - fluidized bed granules neutral substances - l is ktoz (milk sugar) with a particle size of 150÷300 μm, pre-obtained aqueous or aqueous-alcoholic solution of activated - potentiated forms of antibodies to factor a vascular endothelial growth mainly in the ratio of 1 kg of the solution of antibodies to 5 or 10 kg of lactose (1:5 - 1:10) with simultaneous drying in a stream supplied under the grate of heated air at a temperature not exceeding 40°C. the Estimated number 0,07÷0, 17 of the mass of the solid oral form) dried granules, saturated activated - potentiated form of antibodies to growth factor a vascular endothelial loaded into the mixer and mixed with microcrystalline cellulose, enter in the amount of 3.0÷8,0 masses. parts by weight of the total load from the mass of solid oral forms. Then to this mixture 25÷45 mass. parts by weight of the total load "unsaturated" pure lactose (to reduce the cost and some simplification and acceleration of the process without reducing the effectiveness of therapeutic effects) and magnesium stearate in the amount of 0.8÷1.2 masses. parts by weight of the total load. The obtained tablets weight evenly mixed and tabletirujut direct dry pressing (for example, in tablet press Korsch XL 400) with the formation of round tablets weighing 150÷500 mg. After tabletting get a tablet weight of 300 mg, impregnated with a water-alcohol solution (3,0-6,0 mg/tab.) the activated - potentiated the second form of antibodies to factor a vascular endothelial growth in ultra-low dose made with a matrix solution and diluted to 10012in the 10030in the 100200that is equivalent to a mixture of centesimal homeopathic dilution C12, C30 and C200.

For experimental studies have used monoclonal antibodies, cooked to order specialized biotechnology firm.

Example 1

For experimental study of correction of endothelial dysfunction experiments were carried out on white rats male Wistar weighing 250-300 g were divided into 3 groups: group 1 - control received distilled water 9 ml/kg/day (daily intragastric administration.), group 2 - received L-NAME (12.5 mg/kg), group 3 - received L-NAME(12.5 mg/kg) + mixture of solutions of homeopathic dilutions of monoclonal antibody to VEGF - C12, C30, C200 (9 ml/kg/day), each group consisted of 10 animals rats.

Endothelial dysfunction in rats caused a (simulated) by the intraperitoneal administration of N-nitro-L-arginine methyl ester (L-NAME) at a dose of 12.5 mg/kg/day. within 28 days. On the 29th day from the beginning of the experiment under General anesthesia (sodium thiopental (50 mg/kg) catheter in the left carotid artery for recording blood pressure (BP), a bolus of pharmacological agents in the right femoral vein. Hemodynamic parameters: systolic blood giving is giving (GARDEN), diastolic blood pressure (DBP) and heart rate (HR) was measured continuously by a sensor TSD104A and hardware-software complex 100 MP, production Biopac System, Inc., USA. Functional tests: endothelium-dependent vasodilatation (ESV)- intravenous administration of acetylcholine (ach) at a dose of 40 mcg/kg, endothelium-independent vasodilatation (ANSW) - intravenous administration of nitroprusside sodium (NP) at a dose of 30 µg/kg

The degree of development of endothelial dysfunction was assessed by the coefficient of endothelial dysfunction, which is the ratio of the area of the triangle above the trend of the reduction reaction of blood pressure (BP) in response to the introduction of sodium nitroprusside (NP), while the points of the smaller leg is the point of maximum fall AD and point out the AD on the plateau with the introduction of functional tests with the introduction of the NP to the area of the triangle above the trend of the reduction reaction of blood pressure in response to the introduction acetylcholine (ach), and for the shorter of the legs take the difference between the end point of cardiac component and a recovery point HELL with the introduction of functional tests with the introduction of AH, great legs in those triangles are indicators of recovery time vascular reactions to the introduction of AH and TM, expressed in seconds; area calculated triangles of vyrajaetsia arbitrary units (see, for example, a known method described in patent RU 2301015).

When the statistical processing of the data was calculated the mean value, the standard deviation value. The differences were considered significant at p<0,05.

Processing of experimental data when carrying out functional tests on endothelium-dependent (acetylcholine 40 µg/kg) and endothelium-independent (nitroprusside 30 mg/kg/in) relaxation of blood vessels in experimental animals have found that intraperitoneal injection of L-Name at a dose of 12.5 mg/kg for 28 days caused an increase of the coefficient of endothelial dysfunction to 3.5±0,5 used (table 1), whereas in the control group of animals (intragastric administration of distilled water at a dose of 9 ml/kg/day.) QED was 1.2±0,1 usled

In the group of animals that within 28 days were administered L-Name at a dose of 12.5 mg/kg, intragastrically mixture of solutions of homeopathic dilutions of monoclonal antibody to VEGF - C12, C30, C200 QED amounted to 1.7±0,1 used, which was significantly lower than in the group of animals that were administered L-Name.

Thus, the obtained results confirm the possibility of correction L-Name-induced endothelial dysfunction in rats by L-Name at a dose of 12.5 mg/kg by intragastric introduction of a mixture of solutions of homeopathic dilutions of antibodies to VEGF - C12, C30, C200 in the dose of 9 ml/kg, coverages in reducing QED in this group of animals to the level of 1.7±0,1 usled, close to the level of QED in the control group of animals - 1,2±0,1 usled

The data obtained allow us to conclude about the possibility of effective correction of endothelial dysfunction in humans.

1. Remedy for the correction of endothelial dysfunction, characterized in that it contains the activated potentiated form of antibodies to growth factor vascular endothelium.

2. The drug according to claim 1, characterized in that the activated - potentiated form of antibodies to factor a vascular endothelial growth used in the form of activated - potentiated aqueous or aqueous-alcoholic solution, the activity of which is due to the process of multiple serial dilutions in water or water-alcohol solvent in combination with an external mechanical impact - vertical shaking of every dilution.

3. The drug according to claim 1 or 2, characterized in that the solid dosage form that contains an effective amount of granules neutral media saturated with a solution of the activated - potentiated form of antibodies to the growth factor, vascular endothelium, and pharmaceutically acceptable additives.

4. The drug according to claim 3, characterized in that the pharmaceutically acceptable the additives include lactose, cellulose microcrystalline and magnesium stearate.

5. The drug according to claim 2, characterized in that water or water-alcohol solution of the activated - potentiated form of antibodies to factor a vascular endothelial growth obtained by repeated consecutive dilution in combination with external mechanical impact - vertical shaking of every dilution of the matrix solution of antibodies to cytokines with a concentration of 0.5÷5.0 mg/ml

6. The drug according to claim 5, characterized in that the activated - potentiated form of antibodies to factor a vascular endothelial growth used in the form of a mixture of various, mainly centesimal, dilutions on homeopathic technology.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, particularly to therapeutic preparations of mumiyo. The therapeutic preparation which contains purified mumiyo, grapefruit citrosept, edible glycerol, ethanol and water at specific proportions.

EFFECT: preparation has a prolonged shelf life.

8 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, particularly to a composition and a combination for treating panniculopathy and problems associated with venous insufficiency of the lower limbs. The composition for treating panniculopathy and problems associated with venous insufficiency of the lower limbs, containing esculoside and at least one compound selected from icarine or its derivatives, or extracts containing it (them), Gingko biloba dimer flavones in a free form or complexed with phospholipids, amentoflavone and at least one compound selected from escin, escin beta sitosterol complexed with phospholipids, sericoside, sericoside complexed with phospholipids, or Centella asiatica extract in a free form or complexed with phospholipids. The use of the combination on the basis of the mentioned ingredients for preparing the composition for treating panniculopathy and problems associated with venous insufficiency of the lower limbs.

EFFECT: above-described composition and combination are effective in reducing panniculopathy and problems associated with venous insufficiency of the lower limbs.

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely angiology, intensive care, cardiovascular surgery and phlebology, and may be used for integrated treatment of acute thromboembolia of pulmonary artery. That is ensured by prescribing anticoagulants, disaggregants, antibiotic therapy added by thrombolytic therapy by the oral introduction of the preparation Thrombovasim 0.02 mg/kg combined with deobliteration of pulmonary artery or pulmonary trunk by direct surgical thromboembolectomy in complete bypass with retrograde perfusion of pulmonary arteries. Treatment of acute thromboembolia is added by prescribing the preparation Vasaprostan* 60 mcg daily intravenously starting from the moment of diagnosing and up to 7 postoperative days.

EFFECT: method provides higher clinical effectiveness in the patients and preventing developing complications ensured by correction of main pathological links of developing complications of acute thromboembolia of pulmonary artery.

FIELD: medicine, pharmaceutics.

SUBSTANCE: what is presented is the new chemical compound - a 3-(2,2,2-trimethylhydrazinium)propionate derivative - 3-(2,2,2-trimethylhydrazinium)potassium propionate glycinate, (CH3)3N+NHCH2CH2COOKRCOO-, wherein exhibiting endothelioprotective activity. The presented derivative can find application in medicine in the integrated treatment for endothelial dysfunction correction in cardiovascular diseases.

EFFECT: enhanced endothelioprotective properties as compared with previously known mildronat due to the introduction of new functional group showing the most manifested antioxidant properties.

1 tbl

FIELD: medicine.

SUBSTANCE: there are conducted crossectomy, direct and/or indirect thrombectomy, ligation of inadequate perforating veins and varicose flows of subcutaneous vein stems. A pathological venous bed is eliminated by endovasal laser coagulation (EVLC) of the inadequate subcutaneous vein stems. The surgical procedure is performed under tumescent anaesthesia of the EVLC region by physiologic saline cooled to 6-7°C at ozone concentration 4-5 mcg/ml. It is assisted by continuous ultrasonic navigation. The EVLC region involved in varicothrombophlebitis and the incisional wound are processed by argon-plasma flow followed by elastic compression of the operated extremity.

EFFECT: method extends the range of product for treating acute varicothrombophlebitis of the lower extremities.

FIELD: medicine.

SUBSTANCE: gestosis model in Wistar rats is reproduced by the daily intraperitoneal introduction of L-nitro-arginine-methyl ester 25 mg/kg for 14th to 20th day of pregnancy. The simulated pathology is corrected by the subcutaneous introduction of recombinant erythropoietin 50 IU/kg on the 7th, 10th, 13th, 16th, 19th day of pregnancy.

EFFECT: method provides evident placental microcirculation correction.

1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely surgery, and may be used for treating acute thrombophlebitis of lower extremities. That is ensured by the subcutaneous introduction of a mixture containing lydase, heparin and novocaine within a first web space of a foot with underlying conventional therapy. It is added with the introduction of a medicated mixture containint 0.25% novocaine 30 ml; lydase 64 standard units; 1% emoxipin 1 ml; dexamethasone 2 ml; fraxiparine 0.6 ml (11400 IU), sodium adenoside-triphosphate 1 ml; cefotaxime 1 mg; nicotinic acid 2 ml into a dorsal and plantar direction, to a medial and lateral side from the Achilles tendon, as well as around a vein involvement wherein a pathological process of acute thrombophlebitis develops, and into interspinous ligaments of the L2-3-L3-4 lumbar vertebrae. The therapeutic sessions are performed every second day within a therapeutic course of 5-10 procedures to arrest the inflammatory process completely. The therapeutic course is applied once more in 2-3 months.

EFFECT: method provides higher clinical effectiveness, reduced risk of threatening complications and limited progression of the disease due to pathogenetically proved action of surface and deep lymphatic networks of the lower extremities with expected activation of the transcapillary exchange.

2 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely restorative medicine and angiology, and may be used for treating the patients with chronic lymphovenous insufficiency of lower extremities. That is ensured by applying a homogenised gel of brown algae at temperature 28-30°C and wrapping the extremities with non-woven tissues (drapes). That is followed by immediate alternative pneumatic compression by the Lympha-E apparatus on the lower extremities. That involves the ascending wave pressure memorising mode, the II operation mode at pressure 60-90 mm Hg for 40-60 minutes. The procedures are daily, 5 times a week with a pause of 2 days. The therapeutic course is 10-20 procedures.

EFFECT: method provides higher clinical effectiveness at all the stages in any length of the disease including due to additional stimulation of the lymphodrainage function, improved microcirculation, peripheral haemodynamics, improved plasma-coagulation phase of haemostasis, improved tissue trophism.

2 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely surgery, and may be used for sclerosing therapy of hemorrhoid. That is ensured by the sclerosing therapy by introducing a detergent into a hemorrhoid. It is immediately followed by a vibroacoustic session above the sclerosed hemorrhoids. The vibroacoustic session is performed in the frequency range of 0.26 kHz and 0.55 kHz alternatively 30 sec each for 3 minutes.

EFFECT: method provides higher clinical effectiveness ensured by faster relief of the perianal inflammation manifestations, reduced complications and recurrences after a single action of sclerosants.

3 tbl

FIELD: medicine.

SUBSTANCE: group of inventions refers to medicine. Group of inventions involves the use of lisuride or terguride or their enantiomers, or their salts or hydrates for treating and preventing pulmonary arterial hypertension, endogenic or exogenic induced glomerular sclerosis, as well as secondary Reynaud's syndrome; the use of lisuride or terguride or their enantiomers, or their salts or hydrates for treating and preventing said diseases; a pharmaceutical composition for treating and preventing said diseases containing a compound specified in a group consisting of lisuride, terguride, their enantiomers, as well as their salts or hydrates, together with a pharmaceutically compatible carriers, excipients and/or solvents.

EFFECT: group of inventions provides higher therapeutic and preventive effectiveness.

6 cl, 10 ex, 3 dwg

FIELD: medicine.

SUBSTANCE: invention refers to a vaccine containing a combination of non-living antigens of Lawsonia intracellularis, Mycoplasma hyopneumoniae and porcine circovirus, and a pharmaceutically acceptable carrier. The invention also refers to a kit comprising a first container with the non-living antigens of Lawsonia intracellularis, one or more other containers with the antigens of Mycoplasma hyopneumoniae and porcine circovirus, and an instruction for mixing the antigens of Lawsonia intracellularis, Mycoplasma hyopneumoniae and porcine circovirus for preparing one combined vaccine for systemic vaccination.

EFFECT: group of inventions provides the more effective prevention of the diseases caused by these pathogens.

8 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to biotechnology and virology. A composition contains a recombinant nuclear polyhedrosis virus which contains a fused gene. The fused gene consists of a gene coding a partial amino acid sequence of the circumsporozoite protein Plasmodium falciparum and a gene coding a partial amino acid sequence of the viral particle protein gp64. The invention can be used in medicine.

EFFECT: what is presented is a pharmaceutical composition that is an antimalarial vaccine.

8 dwg, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to medicine, namely biopharmaceutics, and may be used for making combined vaccines. For this purpose, the polyvalent combined vaccine contains a type 2 porcine circovirus antigen, and one additional ingredient effective with respect to another organism causing a disease in pigs wherein the type 2 porcine circovirus antigen is a recombinant expressed ORF2 protein of type 2 porcine circovirus specified in: i) a polypeptide containing the sequence SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:9, SEQ ID NO:10 or SEQ ID NO:11, ii) any polypeptide which is homologous to the polypeptide i) at least by 80%, iii) a polypeptide coded by DNA containing the sequence SEQ ID NO:3 or SEQ ID NO:4, iv) any polypeptide which is coded by a polynucleotide which is homologous to the polypeptide iii) at least by 80%, v) any polynucleotide which is coded by the nucleotide sequences SEQ ID NO:3 or SEQ ID NO:4 or any polypeptide coded by the sequences different from SEQ ID NO:3 or SEQ ID NO:4 due to the very 6-20% homology of the sequence, vi) any polypeptide different from SEQ ID NO:5, or any polypeptide different from SEQ ID NO:6, due to the very 6-10% homology of the sequence. What is also presented is a method for reducing a frequency of occurrence or a severity of type 2 porcine circovirus infections.

EFFECT: group of inventions enables producing a high-stable combined PCV2 vaccine.

25 cl, 3 dwg

FIELD: medicine.

SUBSTANCE: invention refers to veterinary virology and biotechnology. What is described is an emulsion inactivated associated vaccine for parvoviral, rheoviral, type I herpes-viral infections and a viral diarrhoeia - cattle mucosal disease (CMD). The vaccine contains a mixture of the concentrated antigen materials of Parvo 32459-DEP parvovirus strains of type I CMD, Reo I - Lang-DEP rheovirus strain of type I CMD, TK-A- (VIEV)-V2-DEP herpes-virus strain of type I CMD and NADL-DEP virus strain of viral diarrhoeia - cattle mucosal disease. The antigen material of the strains is inactivated by 1.2.-aminoethylaziridine. The concentrated and avirulent antigen materials are bound with an adjuvant in the effective relation.

EFFECT: vaccine induces a high level of antibodies to parvoviral, rheoviral, type I herpes-viral infections and viral diarrhoeia - cattle mucosal disease, provides reliable protection of a foetus, newborn calves, young growth of completion of growing and sagination, and also pregnant cows.

4 cl, 5 tbl, 6 ex

FIELD: medicine.

SUBSTANCE: as antigens, vaccine contains a cell suspension of pure culture of E. coli colibacillosis, Str. pneumoniae streptococcus agents and rabbit hemorrhagic disease virus prepared by sampling the affected organs of dead rabbits of a local epizootic centre.

EFFECT: invention provides higher specificity and efficacy of the associated colibacillosis, streptococcus and rabbit viral hemorrhagic disease vaccine eliminating an adverse side effect on animals, and also can be used in research and manufacturing facilities involved in biological engineering.

1 tbl

FIELD: medicine.

SUBSTANCE: affected organs of dead rabbits from a local epizootic centre are sampled to prepare a suspension, and differential-diagnostic mediums are inoculated; pure-growth agents are recovered; separately, E. coli, Str. pneumoniae cultures are grown in a meat-peptone broth with glucose added to the concentration of 0.2% and titre 4-5 billion microbial cells in 1 cm3; then rabbits are infected with a hemorrhagic disease virus of the activity not less than 103.0 LD50/cm3, and liver of dead rabbits is used to prepare 10-15% suspension; thereafter the agent cultures are separately inactivated with formalin to the final concentration no more than 0.4% at temperature 37°C for 4 days or less; then the mixed inactivated cultures are added with an adjuvant presented by aluminium hydroxide gel in the amount of 20 vol %; the end product is thoroughly mixed before packing.

EFFECT: invention provides producing a harmless, high-immunogenic storage-stable vaccine.

1 tbl

FIELD: medicine.

SUBSTANCE: group of inventions refers to veterinary immunology. A combined vaccine of i) an avirulent isolate of Lawsonia intracellularis and ii) attenuated bacteria of Salmonella spp. effective for treating and/or preventing an infection caused by Salmonella spp., and iii) attenuated bacteria of Erysipelothrix rhsiopathiae effective for treating and/or preventing an infection caused by Erysipelothrix rhsiopathiae with such combined vaccine to be introduced in an animal which is other than a human for treating, preventing an infection and/or for relieving clinical symptoms caused by Salmonella spp. and Erysipelothrix rhsiopathiae Kits containing said immunological agents in one or more containers.

EFFECT: invention provides higher clinical and/or preventive effectiveness in said diseases in pigs.

14 cl, 5 tbl

FIELD: medicine.

SUBSTANCE: vaccine contains an active substance and a target additive. As the active substance, the vaccine contains a mixture of an avirulent purified antigen material of La Sota strain of ND virus. of fam. Paramyxoviridae, subfam. Paramyxovirinae, gen. Avulavirus, serotype 1, of an arivulent purified antigen material of H-52 strain of IB virus, fam. Coronaviridae, gen. Coronavirus, serotype Massachusetts, of an arivulent purified antigen material of BISS No. 113 strain of EDS-76 of fam. Adenoviridae, gen. Aviadenovirus, serotype 3, collection of FGU VGNKI BISS No. 113 DEP, of an arivulent purified antigen material of K-58 strain or BG strain of IBD virus, of fam. Birnaviridae, gen. Avibirnavirus, collection of FGU VGNKI K-58 No.122-DEP or BG 102 DEP respectively, or of an avirulent purified antigen material of 1133 strain of RTV virus, fam. Reoviridae, gen. Orthoreovirus, collection of FGU VGNKI 1133 - DEP taken in proportions 0.5:2.0:0.5:1:1 respectively and in the amounts to provide protective immunogenic activity of each antigen in a body after a target preparation has been introduced. As the target additive, the vaccine contains the oil adjuvant Montanide ISA- 70 VG.

EFFECT: invention provides induction in vaccinated poultry of high antibody level to ND, IB, EDS-76, IBD and RTV agents in 28 days after application of the vaccine which appears to remain unchanged for 12 days and transovarially transmitted to offsprings.

8 cl, 6 tbl, 10 ex, 5 dwg

FIELD: biotechnology.

SUBSTANCE: the invention relates to biotechnology and immunogenic compositions containing plasmid for expression of membrane antigen of hepatitis B virus (HBsAg). The said plasmid includes: (1) the sequence which encodes HBsAg, which has an aminoacid sequence SEQ ID NO:3; (2) a promoter of the glyceralgehyde-3-phosphate dehydrogenase, positioned above, to control the expression of the sequence which encodes HBsAg, and the promoter contains a gene sequence SEQ ID NO:1; and (3) the transcription terminator ARG3, positioned below the sequence which encodes HBsAg, where the terminator includes SEQ ID NO:8.

EFFECT: HBsAg can be purified and used to produce vaccines and, in particular, in production of monovalent and combined vaccines.

40 cl

FIELD: medicine.

SUBSTANCE: there are offered versions of antibodies specific to CD22 epitope located from amino acid 22 to amino acid 240 CD22. There are disclosed: a coding polynucleotide, an expression vector, a based host cell and a method of producing an antibody with the use of the cell. There are described versions of a method of CD22 detection on the basis of the antibodies. There are disclosed versions of the CD22 immunoconjugate and based pharmaceutical compositions for treating disturbed B-cell proliferation, and also versions of a method of treating with the use of the pharmaceutical composition. There is disclosed a method of B-cell proliferation inhibition on a basis the immunoconjugate. There are described versions of an engineered cystein-substituted antibody specific to CD22 with one or more free cysteines of thiol reactance within the range 0.6 to 1.0. There are disclosed versions of the "antibody-drug" conjugate, the immunoconjugate and pharmaceutical formulaitons for treating disturbed B-cell proliferation. There are also described a method for protein CD22 detection in a sample on the basis of the immunoconjugate, a method for B-cell detection and a method of treating a malignant tumour on the basis of the "antibody-drug" conjugate. There are disclosed: a product for treating disturbed B-cell proliferation on the basis of the pharmaceutical formulation and a method of producing the "antibody-drug" conjugate.

EFFECT: use of the invention provides new specific CD22 antibodies and the based drugs of acceptable therapeutic efficacy with lower toxicity that can find application in therapy of tumours.

227 cl, 25 dwg, 16 tbl, 14 ex

FIELD: veterinary science, virology.

SUBSTANCE: invention proposes inactivated vaccine against pneumogastroenteritis in cattle and calves. Vaccine comprises a mixture of inactivated viruses of infectious rhinotracheitis, viral diarrhea, rota-, corona-, respiratory-syncytial infection and parainfluenza-3 of cattle and adjuvant. Suspensions of viruses in the mixture are taken in the ratio = 1:1:1:1:0.5:0.5, respectively, by volume. The titer value for viruses of infectious rhinotracheitis, viral diarrhea, rotaviral and coronoviral infection = 107.0 - 108.5 TCD50/ml and for viruses of parainfluenza-3 and respiratory-syncytial infection = 106.5 - 107.5 TCD50/ml. Also, invention proposes a method for prophylaxis of total pneumogastroenteritis in cattle and calves involving administrations of such vaccine. The proposed vaccine is more effective and shows enhanced immunogenicity that provides enhancing the prophylactic effect in its using. Invention can be used in animal husbandry.

EFFECT: improved, enhanced and valuable properties of vaccine.

2 cl, 4 tbl

Up!