Preparation possessing antiviral and immunocorrecting effect

FIELD: medicine, biopharmacology, immunology.

SUBSTANCE: invention relates to manufacturing curative-prophylactic preparations based on leukocyte interferon and natural cytokines. The preparation based on complex of natural cytokines is prepared by induction of human leukocytes with Newcastle disease virus of strain "H". Indicated complex of natural cytokines is prepared by at least two treatments of leukocytes before induction stage with virus with the same natural complex of cytokines prepared in previous stage of induction. Complex is purified from foreign proteins of inductor and comprises 104 IU of antiviral activity of human interferon-alpha in one ampoule, not less, and cellular cytokines, phosphate buffer for maintaining pH 6.9-7.5, sodium chloride and mannitol. The end product is lyophilized for preparing the injection preparation. Invention provides increasing activity of the preparation and to retain the natural complex of cytokines.

EFFECT: improved preparing method, valuable medicinal properties of preparation.

3 cl, 2 ex

 

The invention relates to biopharmacology, immunology, in particular to the production of therapeutic and preventive drugs on the basis of leukocyte interferon.

Leukocyte interferon or interferon-alpha, the secretory cells in response to the action of the inductor is one of the most important factors in protection against viral infections, as well as an activating effect on the immune system of the body. It is known that leukocytes in the complex with the protein interferon-alpha produce and other active proteins-cytokines, and this complex of biologically active proteins secreted by leukocytes exposed to inducers of different nature, is a highly effective immunocorrector, opens up new possibilities in the treatment of viral, bacterial, mixed infections and certain cancers (1).

Known drug "Locteron for the treatment and prevention of viral diseases, which contains human leukocyte interferon synthesized by leukocytes in the blood under the influence of the inductor strain of parainfluenza virus 1 Sendai STB No. 2339, concentrated and purified by micro - and ultrafiltration, containing not less than 8000 ME in the ampoule antiviral activity of interferon-alpha and cellular mediators with mm 10-100 KD, ovalbumin - not more than 1 ng/ml, free of antibiotics and geari the a and containing sodium chloride to a final concentration of 0.9 wt.%, and a stabilizer such as lactose or polyvinylpyrrolidone or mannitol (2). However this drug is not high enough purified and used for local application.

Known for the preparation of purified human leukocyte interferon for injection (CLI) with activity from ME 100 thousand to 1 million ME/mg protein interferon-alpha (3). However, after the concentration of interferon-alpha it contains almost no other cytokines.

Known for the preparation of human leukocyte interferon obtained by the induction of cells by the virus of Newcastle disease, and containing other biologically active proteins and which have antiviral activity of interferon-alpha 1000 IU vials (4). However, the content of interferon-alpha and other cytokines in the product is low, and if further purification is even lower. This drug is adopted as the nearest equivalent.

The technical result of the invention is to increase the activity of the preparation containing interferon-alpha in complex with the natural cytokines, and expanding the range of drugs immune correcting action.

The invention consists in the creation of the drug, which has antiviral and immunokorrigiruyuschy action, on the basis of a complex of natural cytokines obtained by induction of human leukocytes virus Newcastle disease ..... the m "H", while it contains a complex of natural cytokines obtained by sequential multiple (at least two) processing different batches of human leukocytes to the stages of induction by virus of the same natural complex of cytokines obtained at the previous stage of induction and synthesis, purified from foreign proteins inductor containing one vial of not less than 104IU of antiviral activity of human interferon-alpha and cellular cytokines and sodium chloride to a final concentration of 0.6 to 0.9%, phosphate buffer to maintain pH 6.9-7.5 and the stabilizer is mannitol at a final concentration of 1 mg/ml

According to the invention using a combination of interferon-alpha with other natural cytokines with constantly high activity obtained during the induction of cells with virus, for subsequent processing of leukocytes to the processing stage of the virus-inducer, the so-called priming effect, allows to obtain a more pronounced subsequent priming effect and to increase the yield of interferon-alpha and other cytokines. After a few treatments to increase the biological activity of a complex of cytokines stabilization comes at a high level cytokineproducing activity of the cells, induced by the virus. Thus obtained product with further purification after removal of the low is molekulyarnyh compounds and metabolites without fractionation and resultant deposition rates preserves the complex nature of the cytokines with the composition, close to nature, which provides a high biological and clinical effect. Under the influence of the virus leukocytes produce a number of mediators of the immune response - cytokines, providing activation key effectors of macrophages/monocytes, T lymphocytes, neutrophils, EC-cells, cytotoxic macrophages, etc. the spectrum of cytokines, as defined in the drug, is not limited to IFN-alpha, IL-1, IL-6, IL-8, TNF-alpha, factor inhibition of migration of macrophages (MYTH), and contains other cytokines in their natural ratio.

The invention is illustrated by the following examples.

Example 1

To obtain the drug at the first stage for priming drug use, containing cytokines and native human leukocyte interferon-alpha activity 1000-2000 IU/ml in the required dilution and after biosynthesis using as inductor of Newcastle disease virus strain "H" received the product with the activity of interferon-alpha 4000 IU/ml

The second and subsequent stages.

Previous drug from the first stages with the activity of interferon 4000 IU/ml is used for priming in standard dilution prior to administration of the virus-inductor and after biosynthesis of the release of interferon-alpha is already 8000 IU/ml this drug is used for the new Primerose processing of the cells producing the in interferon-alpha in standard dilution and after biosynthesis of the release of interferon-alpha is already 16000 IU/ml This drug again used for priming in standard dilution and after biosynthesis of the release of interferon-alpha is already 32000 IU/ml of Recent drug use again for priming in the standard breeding, but after biosynthesis of the release of interferon-alpha again equal to 32000 IU/ml If the next cycle activity by interferon-alpha is again 32000 IU/ml, such a drug routinely used for Primerose processing cells-producers. That allows you to get a drug with high activity by interferon-alpha, i.e. not less than 104/amp together with other cytokines. Next, the product is sterilized, cleaned of foreign proteins of the virus-inductor, preparing a dosage form, sterilized by filtration, lyophilizer to obtain the drug for injection.

Example 2

The first stage. For priming use of native human interferon-alpha with an activity of 1000 IU/ml in the appropriate dilution, which in addition to interferon-alpha (IFN-alpha) contains 0.4 ng/ml tumor necrosis factor-alpha (TNF-alpha) and after biosynthesis resulting output of IFN-alpha with an activity of 3000 IU/ml and the content of TNF-alpha of 0.87 ng/ml Received the drug is used for the following processing of a new portion of cells-producers in the required dilution prior to administration of the virus-inductor and after biosynthesis output interferon is alpha is already 8000 IU/ml, and for TNF-alpha 2.0 ng/ml the drug again used for Primerose processing cells-producers and after biosynthesis in response to viral induction of the output is for interferon-alpha already 16000 IU/ml, and TNF-alpha of 6.3 ng/ml This drug again used for Primerose processing cells-producers before virusinduced the synthesis of cytokines and the release of IFN-alpha is already 32000 IU/ml and TNF-alpha from 6.4 to 8.4 ng/ml Further repeated cycles do not lead to increased biosynthetic activity of cells-producers and this drug is used for further obtaining and purification of the drug with the final sterilization, lyophilization and determination of the biological activity. The drug is tested for toxicity, specific safety, sterility.

Research on the specific activity. The product must contain not less than 104IU/amp antiviral activity of interferon-alpha.

The determination is carried out in primary trypsinization culture cells of skin and muscle tissue of human embryos, diploid or transplantable cell lines that are sensitive to interferon-alpha (preparation of the CCA activity 42-28-90-P in these cultures must have a titer in the range from 500 to 4000 units).

Obtain transplantable human cells.

Cells grown in the wells of tablets or vials. When the work is e on transplantable cell lines (for example, M-19 and others) they are grown in mattresses on THE 64-3-181-76, with a capacity of 1 l of medium No. 1.

In the mattress to form a monolayer injected (50±5) ml of Versene on FS 42-65 SU-93 at a concentration of 0.02%, preheated (37±1)°or a mixture of 0.02% solution of Versene and trypsin on FS 42-131 SU-88 at a concentration of 0.25% in the ratio of 1:1, heated to the above temperature. After 5-8 min after swelling of the cells, assessed visually, the environment of the mattress merge, and the mattress is placed in a thermostat at 10-20 min until cells begin to pull away from the glass. Then in the mattress injected 100 ml of medium No. 1, vigorously shaken and the environment repeatedly pipeinput to obtain a homogeneous suspension. A sample is taken for counting the number of cells.

Suspension diluted with medium number 1 to a concentration of 3×105cells in 1 ml and poured into 0.1 ml in the wells of the plates. Tablets incubated in the atmosphere (5,0±0,5)% CO2and (70±5)% humidity at a temperature of (37±1)°C.

Obtain transplantable culture of diploid cells of skin and muscle tissue of human embryos.

A suspension containing 106primary trypsinization cells in 1.0 mg of environment No. 1, is transferred into the mattress of neutral glass with a capacity of 100 ml and incubated for 3 days with (37±1)°C. the Formed monolayer is looking at under the microscope at 100xand in the absence of any degenerative change the response to remove the cells from the glass. To this end, the mattress is poured growth environment and fill in the monolayer with a small amount (not more than 5 ml) of 0.25% trypsin solution, preheated (37±1)°C. the Mattress stand (15±5) min in the incubator until the first signs of slipping of the cells from the glass. The trypsin solution is poured into the mattress pour 20 ml of medium No. 1, several times, his sharply shaken and pipeinput cell suspension directly into the mattress. Then the cell suspension is divided into 2 mattress with a capacity of 100 ml, which also incubated for 3 days with (37±1)°C.

After formation of the monolayer operation of removing the cells from the glass again, taking the culture in mattresses greater capacity. Each passirovannye cells grown in a single mattress, subcultured into two, and achieved their accumulation.

To determine the activity of interferon can be used in cell culture from 10 to 25 passages. The monolayer cells grown in the mattress, with a capacity of 1 l is removed from the glass using trypsin as described above, and suspended in 40 ml of medium No. 1. For the titration cell scatter of 0.1 ml in the wells of the microplate and incubated at (37±1)°in the atmosphere (5,0±0,5)% CO2and (70±5)% relative humidity. After 1-2 days, the cells form a monolayer and can be used for titration. In determining the activity prepare dilutions (medium No. 1, usually twice) issleduemykh samples and CCA activity 42-28-91-93 (whose activity is expressed in international units - ME) to values close to the estimated titer. At each dilution do not use less than 4 holes (tubes) with culture. Of holes (tubes) remove the environment and contribute accordingly 0.1 or 1.0 ml dilution of samples. As a control also leave 4 holes (tubes) and replace them Wednesday at the latest. In addition, 16 holes (tubes) leave to control the dose indicator virus. The culture incubated overnight at 37±1)° (culture in tablets in the atmosphere (5,0±0,5)% CO2and (70±5)% humidity). Then to each well with the dilution of the test sample or CCA bring a pre-dose indicator vesicular stomatitis virus (air force) strain "Indiana", corresponding to a given culture 100 TCD500.1 ml. Simultaneously determine the correct dose of the virus, infecting abandoned wells with dilutions of the working dose air force 10-1, 10-2and 10-3environment No. 1. At each dilution spend at least 4 holes (tubes). Infected cultures are incubated further in the above-described mode in 1-2 days, and then examined under a microscope at magnification 100x.

Profitability analysis is recommended when the dose entered the air force corresponds to 100 TCD50- when expressed viral degeneration monolayer in breeding working dose of 10-2. While in control of Manolo the cells should remain unchanged and should not have signs of degeneration.

The titer of interferon take breeding, in which at least 50% of the cells remain protected from the cytopathic effect of the virus. Conversion activity in ME is performed by the formula

Studies on toxicity. The drug should be non-toxic. Control on the lack of toxicity determined simultaneously on cell cultures and animals.

a) Using monolayer cultures of fibroblast cells human diploid fibroblasts M-19, M-21 or transplantable lines used for determining the biological activity of interferon.

Cells grown in 96-well tablets with a flat bottom. In wells with 1-3 daily culture to form a monolayer contribute to 0.1 (or 1.0 ml) dilution 10-1preparation in medium No. 1 of the following composition environment No. 199 or Wednesday Needle with 5-10% bovine serum, 100 u/ml penicillin and 50 u/ml streptomycin.

For each test series are used not less than 3 holes.

In the wells with the control culture contribute the appropriate amount of medium No. 1 without preparation. The culture is incubated for 3 days at (37,0±1,0)°With, on tablets in the atmosphere (5,0±0,5)% CO2according to GOST 8050-86, humidity (70±5)%, and then looking under a microscope at magnification 100x.

The cell monolayer should be a direct relationship is established, not have signs of degeneration and not different from the control.

In case of occurrence of degeneration in the test hole control again, and when it reappears degeneration of cells in the normal monolayer in the control cultures, the preparation reject.

b) When testing toxicity in animals three rabbits weighing 1.5-2.0 kg injected into the ear vein of the drug at the rate of 0.5 ml per 1 kg Under observation for 7 days, the rabbits should be to stay healthy and not lose weight.

Parallel to the preparation 0.5 ml injected intraperitoneally outbred white mice weighing 17-20 g with a speed of 0.1 ml/min While monitoring within 7 days of the mouse must stay healthy and not lose weight.

Each series is controlled by at least 5 mice.

Research on specific safety. The drug should not contain infectious virus-inductor. Complete inactivation of the virus is controlled by two methods using chick embryos and culture of fibroblasts of chicken embryos.

a) When the control on chicken embryos using 10-day chicken embryos, which is injected 0.2 ml of the drug in allantoin cavity with a syringe. In every series expend not less than 5 chick embryos.

After incubation of the infected embryos within 2 days in case of (37±1)°With them are browsing through boscofamily should ostabat the Xia alive. From each embryo individually sucked off allantoin liquid and, without merging, check for the presence of virus in the reaction of haemagglutination with erythrocytes cock. To do this, in the wells of polystyrene plates on THE 6-06-1609-77 prepare serial twofold dilution allantoine liquid solution of sodium chloride according to GOST 4233-77 at a concentration of 0.9%, then each well is injected with equal volumes of 0.5%suspension cock erythrocytes 0.9%solution of sodium chloride. The results account for 20-30 min after sedimentation of red blood cells in the control wells containing erythrocyte suspension and an equal volume of sodium chloride solution.

There should be signs of haemagglutination. When the death of at least one embryo or the presence of haemagglutination control repeat to double the number of embryos. In case of repeated destruction of embryos or positive reactions hemagglutinate the drug is rejected.

b) Control fibroblasts of chicken embryos is carried out in the monolayer culture, which is grown in tablets on the environment No. 1. Sowing dose should be 5×104cells in 0.1 ml per well.

The cell culture plates are incubated at a temperature of (37±1)°C in an atmosphere of CO2(5,0±0,5)% humidity (70±5)% to the formation of the monolayer (2-3 days), then the environment No. 1 drained and contribute to the wells with 0.1 ml of 10-1cultivation Le is centerone of the ampoule in the environment No. 1. For each drug use 4 holes (tubes). In the control culture (4 holes or tubes) enter the appropriate amount (0.1 ml) of the environment No. 1. The culture is incubated for another 3 days, then viewed under a microscope at magnification 100x. The monolayer should remain intact, with no signs of cytopathic effect.

If there are signs of degeneration, the repeat control.

When you identify the cytopathic effect of the drug and the normal state of the monolayer in the control culture reject the drug.

Determination of tumor necrosis factor (TNF).

To determine the TNF is using the immunoassay method or cytotoxic test in the cell line of skin and muscle tissue of mouse L-929.

When the determination by ELISA uses a monoclonal antibody to TNF biotinylated and the conjugate of horseradish peroxidase with streptavidin. The technique of setting reactions described below to determine non-specific impurities.

When determining TNF in the cytotoxic test culture of mouse cells L-929 grown with strict observance of the conditions of sterility in the mattresses of neutral glass in the growth environment No. 1.

With the camera Goryaeva counted under a microscope in suspension the number of cells and bred her environment No. 1 to a concentration of 6×104cells in 1 ml of Sowing dose amitraz capacity of 1 l is equal to 6× 106cells or 100 ml of the prepared suspension. Cells incubated with t° 37±0,5°C. the Monolayer control under the inverted microscope of any model under magnification 100x. Culture should not be signs of bacterial gains and not typical for fibroblasts inclusions. When removing the cells from the glass monolayer pour 50,0 ml of 0.25%trypsin, preheated (37±0,5)°S, and incubated (6±1) min, controlling the swelling of the cells, which is estimated visually. Then the trypsin solution is drained and put the mattress in the unit (37±1)° (8±2) min order cells began to pull away from the glass, which is also controlled visually. The mattress is injected to 50.0 ml of medium 1 and vigorously shake it. This should ensure that the drift cells in the environment. Wednesday repeatedly pipeinput 1-2 min to obtain a homogeneous cell suspension, rinsing jet growth surface. For accumulation of culture at each subsequent passirovannye cells grown in a single mattress, subcultured at three or four. With the camera Goryaeva counted under a microscope at magnification 100xthe number of cells, plant with medium number 1 to a concentration of 3×105cells in 1 ml and dispensed in 96-well tablets with a flat bottom on THE 64-2-278-79 0.1 ml in each well using an automatic micropipette any model. ICRI is tablets incubated in CO 2-incubator (37±1)°and the level of CO2-5% before the formation of the monolayer, which is controlled under an inverted microscope at magnification 100x. Usually after 1-2 days of growth the cells form a monolayer and can be used to determine TNF.

When determining TNF in a supportive environment No. 2 prepare two-fold dilution of the samples and, in particular TNF to values close to the estimated titer.

The composition of the medium 2: medium No. 199 with 2% CARRIED (heated), actinomycin-D company Sigma (USA) at a concentration of 0.5 μg/ml

At each dilution do not use less than 4 holes with culture. From the wells to remove the environment No. 1 and contribute to 0.1 ml of the dilution of the samples in the environment No. 2. As a control, left 4 holes, and replace the environment No. 1 on Wednesday, the No. 2 at 0.1 ml per well. Tablets incubated in the above-described mode for 1 day, followed by analysis under an inverted microscope at magnification 100x. Under the action of TNF as a result of its cytotoxic activity of the cells die, and the monolayer collapses. For the title TNF take the breeding of the investigational product, in which at least 50% of cells die due to a cytotoxic effect. The drug should cause a cytotoxic effect in the cultures of L-929 in the breeding of not less than 1:100, which corresponds to 50 ng/ml TNF.

The product should not contain the impurities egg albumin. To determine the use enzyme immunoassay (ELISA) with a sensitivity of at least 1 ng/ml.

The drug should not be surface antigen hepatitis b virus, antibodies to hepatitis C virus, antibodies to human immunodeficiency virus (HIV 1, 2).

The drug has a pronounced antiviral and immunomodulator activity, shows the ability to stimulate proliferation, differentiation and functional activity of immunoregulatory subpopulations of T-lymphocytes (mainly T-helper cells(CD4+), although it can be corrected and T cells with CD8+ cluster, for example, acute radiation sickness, cancer. The drug stimulates the blood and can be used to overcome drug cytopenias (anemia, leukopenia, lymph and thrombocytopenia), without any other preparatov. Anti-inflammatory effect is the acceleration of normalisatie indicators kallikrein-kinin system, the content of late proteins of acute phase of inflammation.

Thus, declared the drug has a high activity of interferon-alpha and a wide range of natural cytokines through techniques that allow you to keep present in the cells and the secretory their complex of biologically active proteins.

References

1. V.P. Kuznetsov, Dlesel and other Prevention and treatment of influenza and other respiratory drugs interferon". In the collection of scientific papers "Viral infection", , Ekaterinburg, 1993, p.51-62.

2. EN 2108804 C1, publ. 20.04.1998.

3. Iasevoli, Bchydro, Munzarova, Lsearch and other "experience in the use of human leukocyte interferon in relapsing-remitting course of multiple sclerosis, Neurological Bulletin, Kazan, "Medicine", 1997, thhh, issue 1-2, p.58-61.

4. V.P. Kuznetsov, Dlese, Ban "the Concept of immune multifactor immunodeficiency, infectious diseases and cancer", Journal of Microbiology, epidemiology and Immunobiology, Moscow, 1996, №5 press, p.104-110.

1. The drug, which has antiviral and immunokorrigiruyuschy action on the basis of a complex of natural cytokines obtained by induction of human leukocytes by Newcastle disease virus strain "H", followed by separation of the target product, wherein the product contains a complex of cytokines obtained by not less than twice the processing of cells to the induction stage of the virus in the same natural complex of cytokines obtained in the previous phase induction cleared of alien proteins inductor containing one vial of not less than 104ME and antiviral activity of human interferon-alpha and cellular cytokines, phosphate buffer to maintain pH 6.9-7.5, the sodium chloride to a final concentration of 0,60,9% and stabilizer.

2. The preparation according to claim 1, characterized in that the target product lyophilizer to obtain injectable.

3. The preparation according to claim 1, characterized in that the stabilizer is used mannitol at a final concentration of 1 mg/ml



 

Same patents:

FIELD: medicine, gastroenterology, pharmacy.

SUBSTANCE: invention relates to agents used in treatment of ulcerous-erosion injures in gastroduodenal region. Method involves diluting 100 mcg of dry lyophilized powder of immunomodulating agent "Superlimf" in 3-5 ml of 0.9% isotonic solution and irrigation of ulcer or erosion with this solution 1 time per a day by the endoscopy method. The treatment course is 3-4 procedures with break for 4-5 days. Method provides alteration of cytokine pattern of tissues, induction of influx of mononuclear phagocytes to the injure focus that results to localization of inflammation and the complete epithelization of ulcers and erosions.

EFFECT: improved and effective method for treatment.

1 ex

FIELD: medicine, pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to a method for preparing an anti-inflammatory, wound-healing, capillary-strengthening, immunomodulating agent. Method for preparing an anti-inflammatory, wound-healing, capillary-strengthening, immunomodulating agent is carried out for four stages. At the first stage violet tricolor and/or field milled herb is extracted with fluidized carbon dioxide under the definite condition followed by separation of grist from lipophilic fraction of extract; at the second stage defatted grist is subjected for three-fold extraction by remaceration method under the definite condition followed by treatment and purification of combined extract, treatment, condensation and preparing liquid alcoholic extract; at the third stage liquid alcoholic extract is used for preparing polysaccharide and flavonoid complexes by precipitation of polysaccharide with three-fold volume of 96% ethyl alcohol and the following drying at the definite temperature; at the forth stage grist after isolation of polysaccharide and flavonoid complexes is used for preparing pectins by treatment with three-fold volume of ammonium oxalate solution at the definite temperature, evaporation and drying. Liquid alcoholic is evaporated to 1/5 of the parent volume, dried by spraying drying or lyophilic drying at definite temperatures. Each end product prepared at each stage can be used as both independent medicinal formulation and can be used for preparing other medicinal formulations (tablets, capsules, suppositories, films). Also, invention relates to a method for preparing an anti-inflammatory, wound-healing, capillary-strengthening, immunomodulating agent that involves extraction of violet tricolor and/or field milled herb with 70% ethyl alcohol by infusion for a definite time followed by purification of the end product, settling at the definite temperature and filtration. Method provides preparing agent with broad pharmacological pattern of action and provides the maximal using the medicinal vegetable raw.

EFFECT: improved preparing method, valuable medicinal properties of agent.

5 cl, 5 tbl, 17 ex

FIELD: medicine.

SUBSTANCE: means has lipid fraction obtained from Berryteuthis Magister Comandor squid liver containing 10% of polyunsaturated fatty acids and 50% of alkyl-diacylglycerides showing marked lipid-correcting and immunomodulating properties.

EFFECT: enhanced effectiveness in treating lipid metabolism disorders and immunity system disorders.

4 tbl

FIELD: medicine.

SUBSTANCE: method involves administering inmmunotherapy with recombinant interferon-α2b in daily dose of 3x106 MU. It is incubated in thermostat during 1 h at 37°C with 100 ml of autoblood and then it is intravenously introduced to a patient during 1-1.5h daily under blood formula control to reach leukocyte content of>4*109 /l, granulocytes >2*109 /l.

EFFECT: eliminated leukopenia and dose-limiting toxicity risk; accelerated treatment course; reduced risk of infectious complications.

FIELD: agriculture, veterinary science.

SUBSTANCE: during the 1st d after forming raising groups one should once inject intramuscularly a solution of "Complex A" preparation at the dosage of 0.30-0.32 mg/kg body weight for 45-60-d-aged piglets and simultaneously with fodder one should introduce "Lactobifadol" preparation at the quantity of 0.50-0.52 g/kg body weight during the first 1-5 d. The present innovation enables to activate immune system, increase total protein and hemoglobin in blood that in its turn, prevents bronchopneumonia and remove stress in piglets after forming special raising groups.

EFFECT: higher efficiency of prophylaxis.

1 ex, 1 tbl

FIELD: medicine, ophthalmology.

SUBSTANCE: as an immunomodulating remedy one should introduce tamerite per 0.5 ml subconjunctivally and per 1.5 ml i/m daily for 5 d. The method provides normalization of immunity values due to additional local complex manifestation of immunomodulating, antiphlogistic, antioxidant and regenerating effects of tamerite.

EFFECT: higher efficiency of complex therapy.

2 ex

FIELD: food industry.

SUBSTANCE: invention relates to food additives that can be used to prevent immunodeficiency conditions. Immunomodulator is prepared via homogenization of lymphatic nodes in sodium chloride solution, autolysis, centrifugation, heating of supernatant to 80°C, cooling, removal of precipitate, and drying of supernatant by cooling it and placing it into atmospheric sublimation installation followed by subsequent post-drying using IR drying technique.

EFFECT: simplified immunomodulator preparation process and preserved biological and food values of finished product without creation of special temperature regime.

5 tbl, 2 ex

FIELD: applied immunology.

SUBSTANCE: composition contains, wt parts: borax decahydrate1-25, sodium thiosulfate pentahydrate 10-5-10-4, potassium carbonate 30-150, refined sugar 30-200, and water 100-200 per 100 wt parts of sodium metasilicate pentahydrate. In addition to its capability of improving resistance to diseases, body weight increase, productivity of agricultural plants, quality of crop, and ripening term (harvest time), composition according to invention possesses nonspecific immunostimulating activity, including production of antibodies and enhancement of immunity through activation of immunocytes thereby maximally strengthening vaccination effect regarding diseases caused by malignant neoplasm viruses.

EFFECT: increased assortment of immunostimulating agents.

10 cl, 11 dwg, 12 ex

FIELD: medicine, immunology, veterinary science, pharmacy.

SUBSTANCE: invention concerns a medicinal agent modulating the immune response of body. Agent is made as a tablet covered by envelope. The table core comprises thymus preparation, sodium nucleate, potato starch and the accessory substances taken in the definite ratio of components. As the thymus preparation immunomodulating agent can comprise tactivine or thymaline, or thymogen. The core is covered by envelope comprising acetylphthalylcellulose, castor oil, vaseline oil, titanium dioxide, tropeolin "O" taken in the definite ratio of components. Invention expands assortment of immunomodulating agent by the development of immunomodulating agent that acts on T- and B-lymphocytes simultaneously and on macrophage link of immune system that is suitable in using by children and other patient groups for a long time wherein injection method of administration is not desirable. The immunomodulating agent "Ribotab" elicits high effectiveness providing correction of immunity by tableting agent "Ribotab" after its using in a single dose.

EFFECT: improved and valuable properties of agent.

2 cl, 2 tbl, 5 ex

FIELD: medicine, pediatrics, pulmonology.

SUBSTANCE: in blood serum under testing one should detect the level of specific IgE-AB to S. pneumoniae antigen and at its value being above 0 kU/l it is necessary to perform single vaccination with "Pneumo 23" preparation at the dosage of 0.5 ml intramuscularly regardless of the period of exacerbation at the background of basic therapy. The present innovation enables to increase immunity that in its turn increases efficiency of pharmacotherapy at bronchial asthma and decreases sickness rate at ARVI.

EFFECT: higher efficiency of prophylaxis.

2 ex

FIELD: biotechnology, immunology, veterinary science.

SUBSTANCE: invention proposes the preparation that represents 9,0-11.0% immunoglobulins solution of horse blood serum with pH value from 7.0 to 7.5. The content of γ-globulin fraction in this preparation is 90.0%, not less, of the total protein amount. The preparation comprises albumin, α- and β-globulin fractions as nonspecific impurities in the amount 10.0%, not above, and residual ethyl alcohol in the amount 4.0%, not above. The preparation is apyrogenic, non-toxic and sterile.

EFFECT: valuable properties of preparation.

1 tbl, 1 ex

FIELD: organic chemistry, microbiology.

SUBSTANCE: invention relates to new synthetic biologically active derivatives of pyrimidine, namely to 2,4-dioxo-5-(2-hydroxy-3,5-dichlorobenzylidene)imino-1,3-pyrimidine potassium, sodium or ammonium salt of the general formula: wherein X is taken among the group: Na+, K+, NH+4. The claimed substance shows expressed antibacterial activity directed mainly against different fungi, bacteria, protozoan and viruses.

EFFECT: valuable biological properties of compounds.

13 tbl, 13 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to applying compounds of the general formula (1):

as inhibitors of caspase-3 that allows their applying as "molecular tools" and as active medicinal substances inhibiting selectively the scheduling cellular death (apoptosis). Also, invention relates to pharmaceutical compositions based on compounds of the formula (1), to a method for their preparing and a method for treatment or prophylaxis of diseases associated with enhanced activation of apoptosis. Also, invention relates to new groups of compounds of the formula 91), in particular, to compounds of the formulae (1.1):

and (1.2):

. In indicated structural formulae R1 represents inert substitute; R2, R3 and R4 represent independently of one another hydrogen atom, fluorine atom (F), chlorine atom (Cl), bromine atom (Br), iodine atom (J). CF3, inert substitute, nitro-group (NO2), CN, COOH, optionally substituted sulfamoyl group, optionally substituted carbamide group, optionally substituted carboxy-(C1-C6)-alkyl group; R5 represents oxygen atom or carbon atom included in optionally condensed, optionally substituted and optionally comprising one or some heteroatoms; R6 represents hydrogen atom or inert substitute; X represents sulfur atom or oxygen atom.

EFFECT: improved preparing and applying methods, valuable medicinal and biochemical properties of compounds.

3 cl, 1 dwg, 2 tbl, 1 sch, 8 ex

FIELD: veterinary medicine.

SUBSTANCE: vaccine has avirulent antigen material produced from O№112-DEP strain homological virus, protection medium and adjuvant taken in effective proportions. The strain is deposited in micro-organism VGNKI collection under registry number of O№112-DEP. The O№112-DEP strain virus is reproduceable in 9-11 days old SPF-hen embryos having infectious activity of at least 6.9 lg EID50/cm3. The vaccine comprises ethylene imine dimer in 0.1% concentration as inactivation agent. The antigen material is mixed with protection medium after activation and subjected to lyophilization. Before being used, the dried antigen material is solved in adjuvant containing aerosyl, saponin, glycerol and phosphate buffer solution taken in effective proportions. The vaccine is intramuscularly introduced for immunizing clinically healthy 25-30 days old birds in the amount of 0.5 cm3. Immunity comes to a vaccinated bird at the fourteenth-twenty first day after vaccination.

EFFECT: high antigenic and immunogenic activity; no adverse side effects.

8 cl, 5 tbl

FIELD: veterinary medicine.

SUBSTANCE: vaccine has antigenic material produced from La-Sota strain reproduced in 9-10 days old SPF-hen embryos having infectious activity of at least 9.7 lg EID50/cm3 and hemagglutination activity equal to at least 1:512, protective medium and adjuvant of thymogen taken in effective proportions. The protective medium comprises 20% lactalbumin hydrolyzate solution and degreased milk in 1:5 proportion. The vaccine is produced by mixing its ingredients and with following preparation lyophilization. Ready vaccine is dry porous mass of light yellow color. The vaccine is applicable for carrying out specific prophylaxis. The vaccine is introduced as spray at a dose of 1 cm3/head.

EFFECT: high antigenic and immunogenic activity; no adverse side effects.

7 cl, 8 tbl

FIELD: medicine.

SUBSTANCE: method involves treating hepatitis C virus infection or hepatitis B virus infection by introducing carboxamidine of formula 1 or its pharmaceutically permissible salt at a dose of 0.1-40.0 mg/kg of body mass. Α-interferon is also introduced. Compound of formula 1 is in D-configuration.

EFFECT: enhanced effectiveness of treatment.

7 cl, 5 dwg

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of pyrazine of the general formula (I):

wherein R1 means hydrogen (H) or halogen atom; R2, R3 and R5 mean hydrogen atom (H); R4 and R6 mean hydroxy-group optionally protected with acetyl or benzoyl group; A means oxygen atom (O); n = 0; Y means oxygen atom (O), or their salts. Compounds show the excellent anti-viral activity and useful as a therapeutic agent in treatment of viral infections. Also, invention describes a pharmaceutical composition.

EFFECT: valuable medicinal properties of compounds and composition.

7 cl, 2 tbl, 15 ex

FIELD: clinical immunology.

SUBSTANCE: preparation represents 9.0-11.0% solution of horse blood serum immunoglobulins with pH 7.0-7.5 and content of γ-immunoglobulin fraction at least 90.0% of the total protein. Nonspecific fractions in preparation are albumin, α- and β-globulin fractions in amount not larger than 10.0%, and residual ethyl alcohol in amount not larger than 4.0%. Preparation is characterized by virus-neutralizing antibodies against virus Marburg. Titer of virus-neutralizing antibodies is at least 1:2048 and can be used for emergency prevention of Marburg fever in humans.

EFFECT: extended immunoglobulin application area.

1 tbl

FIELD: applied immunology.

SUBSTANCE: composition contains, wt parts: borax decahydrate1-25, sodium thiosulfate pentahydrate 10-5-10-4, potassium carbonate 30-150, refined sugar 30-200, and water 100-200 per 100 wt parts of sodium metasilicate pentahydrate. In addition to its capability of improving resistance to diseases, body weight increase, productivity of agricultural plants, quality of crop, and ripening term (harvest time), composition according to invention possesses nonspecific immunostimulating activity, including production of antibodies and enhancement of immunity through activation of immunocytes thereby maximally strengthening vaccination effect regarding diseases caused by malignant neoplasm viruses.

EFFECT: increased assortment of immunostimulating agents.

10 cl, 11 dwg, 12 ex

FIELD: veterinary virology, biotechnology.

SUBSTANCE: vaccine comprises an avirulent antigen material from the strain "O № 112-DEP" of homologous virus and an oily adjuvant taken in the effective ratio. The strain is deposited in collection of microorganisms VGNKI at registration name "O № 112-DEP". Virus of the strain "O № 112-DEP" is reproduced in SPF-chicken embryos (age 9-11 days) with infectious activity at least 6.0 Ig EID50/cm3. Ethyleneimine dimer in the concentration 0.1% is used as an inactivating agent. Vaccine is used for immunization of clinically health poultry of age 25-30 days in the volume 0.5 cm3 by intramuscular route. In grafted poultry the immunity occurs on 14-21 days after vaccination. Invention provides expanding assortment of inactivated emulsion vaccines against laryngotracheitis in poultry eliciting high antigen and immunogenic activity and harmless.

EFFECT: valuable properties of vaccine.

5 cl, 5 tbl

FIELD: medicine, infectious diseases.

SUBSTANCE: methods involves topical administration of the preparation "Realdiron" in the sting point in the dose 3000000 IU and "Realdiron" is administrated by intramuscular route additionally in the dose 3000000 IU as a single or multiple injections in case later for two days after sting. Invention provides early inactivation of tick-borne encephalitis pathogen in the place of its incorporation into the body, prevents the process of viruses replication that, in turn, promotes to the effective prophylaxis of tick-borne encephalitis in stages of early infection. Invention can be used in prophylaxis of tick-borne encephalitis.

EFFECT: enhanced effectiveness of prophylaxis.

2 ex

Up!