Method for producing hexamethylene tetramine and nanoselenium agent having stimulant action on body cells

FIELD: medicine.

SUBSTANCE: method for producing an agent for stimulating body cells involving preparing a mixture of aqueous solution of selenious acid and PEG 400; that is followed by preparing a mixture of hydrazine hydrochloride and PEG 400; the prepared mixtures are combined; the solution is put to dialyse against distilled water; surplus of water is driven off; the produced solution is added with hexamethylene tetramine; pH is reduced to 7.2-7.4; the method is implemented in certain circumstances.

EFFECT: producing high-effective, ecologically safe agent by the synergism of colloidal selenium and hexamethylene tetramine on body cell stimulation.

1 dwg, 2 tbl, 4 ex

 

The invention relates to the field of pharmacology and medicine, including veterinary medicine, and can be used as a nonspecific stimulant therapy in diseases of different etiology to stimulate the body's cells.

Stimulating effect on the body cells is carried out by acting on the mitochondrial respiration of the cells.

Currently a large number of substances in respect of which shown the ability to increase to increase the metabolic activity of cells through stimulation of mitochondrial respiration[1, 2, 3, 4].

These properties have the most antioxidants[5, 6, 7, 8]. According to this theory, free radicals, resulting from various oxidative reactions in the body, have multiple damaging effects on macromolecules (nucleic acids and proteins, causing their degradation. This theory explains a wide range of associated pathological processes including cardiovascular disease, age-related immunosuppression and brain dysfunction, cataracts, cancer and some others). Produced mainly in the mitochondria of cells the molecules of superoxide (O2), H2O2, hydroxyl radical (HO-), and possibly singlet oxygen ( O2) damage cellular macromolecules (DNA, proteins, lipids) [6, 7, 8, 9]. I believe that reactive oxygen species cause damage to membranes, collagen, DNA, chromatin, structural proteins, and are involved in epigenetic regulation of expression of nuclear and mitochondrial genes, leading to DNA methylation, affect intracellular calcium levels trigger a cascade leading to apoptosis, etc.[10, 6, 11, 9].

During aging significantly altered mitochondrial energetics, in particular, reduced oxidation of succinic acid, as indicated by the data, and the decrease during aging in the tissues of the activity of succinate dehydrogenase [12, 13]. The impact of activating the system of education and the use of succinic acid with antioxidant properties, can be particularly effective in improving the functional capacity of the organism [12, 13]. Feeding sodium succinate sodium to rats at 20 months of age for 1.5 years (300 mg/kg in courses of 10 days at 1 month intervals) led to an increase in average (6.2%, p<0.05) and maximum (12.3%) of their lifespan [3]. The authors, however, do not report the frequency of spontaneous tumors in rats in these experiments.

Inhibitors of cross-linking is considered as one of the possible mechanism�in aging since this process is accompanied by formation of defective macromolecules [14, 16]. Increase with age cross-links experimentally proven so far only for extracellular proteins collagen and elastin and possibly to chromatin [15]. Restriction of caloric intake, which increases the lifespan of animals, retards the accumulation of collagen crosslinks [17].

The decrease with age in the level and metabolism of catecholamines in the brain (mainly in the hypothalamus) and the violation of their relationships with other biogenic amines, particularly serotonin, attach key importance in the mechanism underlying age-related changes in the neuroendocrine system, and ultimately the aging process [18]. Achieved by pharmacological means or electrolytic destruction of the decrease in the content of catecholamines in the hypothalamus reduced the lifespan of the animals and increased the incidence of tumors [19], whereas administration to rats of neurostimulator of pentylenetetrazole reduced morphological changes in the brain associated with aging [20].

At the present stage of science development the main mechanisms of action of metabolic stimulants consider their impact on the bioenergetic processes in neurons and interaction with neurotransmitters. Neurometabolic STI�ulatory promote penetration through the blood-brain barrier and glucose utilization, improve metabolism of purines and pyrimidines, activate protein synthesis, RNA and ATP. The effect of some of neurometabolic stimulants mediated neurotransmitter systems of the brain: monoaminergic (so, piracetam helps increase levels of dopamine and norepinephrine), cholinergic (so, meclofenoxate contributes to the increase in the density of cholinergic receptors and the level of acetylcholine in the synapses), glutamatergic.

Mitochondria are critical for the survival and proper function of almost all types of eukaryotic cells. The mitochondria of virtually any cell type may be congenital or acquired defects that affect their function. Thus, clinically significant signs and symptoms of mitochondrial defects that affect the function of the respiratory chain are heterogeneous and variable, depending on the distribution of defective mitochondria among cells and the severity of their defects and physiological requirements in respect of the affected cells. Non-proliferating tissues with high energy demands, such as nervous tissue, skeletal muscle and cardiac muscle, are particularly sensitive to dysfunction of the mitochondrial respiratory chain, but can be affected any system of bodies.

Diseases and symptoms listed below include known Pat�physiological consequences of dysfunction of the mitochondrial respiratory chain and, as such, are violations for which the tool of this invention have therapeutic applicability.

The symptoms of the disease, secondary to mitochondrial dysfunction, usually associated with 1) the spill-over of free radicals from the respiratory chain; 2) defects in the synthesis of ATP, leading to failure of cellular energy, or 3) apoptosis triggered by mitochondrial release signals, such as cytochrome C, which initiates or mediashout cascades of apoptosis. This is an important clarification of existing dogmas in understanding the pathogenesis of diseases involving mitochondrial dysfunction, and in the understanding of how to treat such violations.

Neurometabolic stimulants also have antioxidant, membrane-stabilizing, neuroprotective and anti-hypoxic effect. Important improvement of microcirculation in the brain by optimizing the passage of red blood cells through the microcirculation and inhibition of platelet aggregation.

The result of the combined action of neurometabolic stimulators is the improvement of bioelectric activity and integrative activity of the brain, which is accompanied by characteristic changes of electrophysiological patterns (increase of the level of wakefulness, facilitate�to the amount of passing information between the hemispheres, the increase of the dominant peak, increased absolute and relative power spectrum of the EEG of the cortex and the hippocampus). Enhancing the exchange of information in the brain, increased cortico-subcortical control, playback commemorative trail lead to the improvement of perception, memory, thinking, attention, improve learning ability, the activation of intellectual functions. The ability to improve cognitive functions are allowed to designate drugs neurometabolic stimulants as stimulators of cognition".

In the spectrum of clinical activity neurometabolic stimulators can distinguish the following main effects: nootropic, mnemotropic, adaptogenic, antiasteniceski, psychostimulant, antidepressant, sedative, vegetative antigenetically, antiparkinsonian, anti-epileptic.

Some of these pharmacodynamic properties inherent in all neurometabolic stimulants, while others were more selective. In clinical conditions each drug is able to implement the full range of its inherent properties, and evaluate each of them in isolation is often not possible.

Originally neurometabolic stimulators were used mainly in the treatment of functional disorders of the brain in elderly patients with organic brain with�ndrama. Recently they have become widely used in various fields of medicine, including geriatric, pediatric and obstetric practice, psychiatry, neurology and addiction.

Recent high rates of research activities aimed at identifying and studying the mechanisms of action of various neurometabolic stimulators. The search continues for the basic hypothesis of the action of neurometabolic stimulators, integrating various aspects of their mechanisms of action. Urgent task remains the search for new drugs class neurometabolic stimulators, which would possess a greater pharmacological activity and would have a more selective effect on integrative functions of the brain, improving mental state of the patient's mental activity and orientation in everyday life.

The results of neurometabolic therapy. The use of neurometabolic stimulants can lead to improvement after the beginning of a comprehensive program of treatment 90% of patients with a variety of disorders. The effect of neurometabolic treatment is manifested in the form: reduce the symptoms until the complete disappearance of insomnia, headaches, dizziness; improvements in processes of remembering and learning information and increase with�osobnosti to concentrate; complete absence or significant reduction of the manifestations of other disorders and disturbances in higher nervous activity.

A method of modifying the functional activity of the cells of the tissue structure of the pathological focus of a living organism (options) (see patent RU, publ. 20.11.2003). The invention relates to medicine, more specifically to selective magnetic therapy, and can be used for the treatment of various diseases by altering the functional activity of the cells of the tissue structures under the influence of external low frequency electromagnetic field. The method includes the impact on the mechanism of transmembrane ion kinetics of the cells of the tissue structure when the mass of 0.05-1.5 kg external alternating low-frequency electromagnetic field, the magnitude of the magnetic induction which, depending on the functional activity of cells is chosen according to the first embodiment in the range of 5-20 MT, which provides a stimulating effect on the functional activity of the cells of the tissue structure according to the second embodiment is in the range of 25-60 MT, providing a depressing effect, while the effects in both options selected in the range of 2-30 min. effect: provision of regular and one-pointedness of repeatability caused by biological and therapeutic effects associated with changes in function�tional activity of the cells of the tissue patterns of pathological, guaranteeing effective treatment. The main disadvantages of this method are the limitations of the object by weight (0.05 to 1 kg) and prolonged exposure to electromagnetic fields.

Also known a method of increasing the functional activity of lymphocytes (see RF patent №2182597, publ. 20.02.2002). The method is carried out by exposure to helium plasma, obtained at a current of 30 A, voltage 20 V and the gas flow 2 l/min, spleen cells, placed in a medium RPMI-1640. The medium further contains 5% inactivated human serum of group IV, 2 mm 1-glutamine, 10 mm Hepes buffer, 5·10-5M 2-mercaptoethanol and 50 µg/ml gentamicin. The exposure is performed for 20 s at a distance of 20 cm from the nozzle of the plasma torch. The method allows locally to influence the functional activity of lymphocytes in cell culture, and within the entire organism, in this case the effect is achieved in a short time. The method can be used in clinical practice as a method of stimulating effect on biological processes in cells and tissues. The main disadvantages of the method are the use of human serum rare group IV, high gas consumption and expensive equipment. In addition, stimulation of immune processes can have both positive and negative consequences for the organism.

Currently �turbine zobretenie aimed at solving the problem of creating a highly effective tool for the stimulation of the body's cells.

The technical result is to obtain the proposed method, which has a high stimulation of the body's cells.

The technical result is achieved by the proposed method of obtaining funds, which contains as active ingredients colloidal selenium and hexamethylenetetramine, as well as water.

In the known authors of the sources of patent and scientific and technical information not described for stimulating cells of the body, representing a colloidal solution of nanoparticles of selenium and hexamethylenetetramine.

It is known the use of hexamethylenetetramine in medicine as an antiseptic (has a dose-dependent bactericidal or bacteriostatic effect). It is also known the use of hexamethylenetetramine in the production of phenol-formaldehyde resins used for production of plastics, adhesives, varnishes, etc.; as food additive preservative E239 used in cheese production and in conservation of red caviar; as "dry alcohol" for cooking and heating food; in analytical chemistry as a component of buffer solutions; as raw material in the manufacture of explosives RDX and hexamethylenediamine; as a corrosion inhibitor.

It is known to use colloidal selenium as antioxidant�th funds. It is known the use of hexamethylenetetramine as a drug for the treatment of urogenital infections.

The authors first identified a new property of colloidal selenium and hexamethylenetetramine in the tool multiple times to strengthen mutual action directed at the stimulation of the body's cells by increasing cellular respiration.

The method of obtaining funds for the stimulation of body cells is that mix 250 µl of 0.5 M aqueous solution se acid with 8 ml of polyethylene glycol 400 (hereinafter PEG 400), intensively stirred on a magnetic stirrer at 750 rpm, pH of this mixture of 7.55, to obtain a mixture 1. Next, 250 μl of 0.5 M aqueous solution of hydrochloric acid make hydrazine in 8 ml of PEG 400, intensively stirred on a magnetic stirrer at 750 rpm, pH of this mixture is 0.68, to obtain compound 2. With vigorous stirring is introduced into the mixture 1 mixture 2 dropwise. Put the resulting solution to dialysis against distilled water to remove the PEG and hydrazine hydrochloric acid. Distilled off the excess water on a rotary evaporator.

In the resulting solution of hexamethylenetetramine is dissolved to a final concentration of 5%. The pH was adjusted to 7.2 to 7.4.

The obtained product contains, mass.%:

Hexamethylenetetramine 5
Selenium0,062
Distilled waterTo 100

The advantage obtained by the proposed method, is that by using nanoparticles based on selenium hexamethylenetetramine is delivered into the cell. The biodynamics of hexamethylenetetramine, United with colloidal selenium occurs by lymphogenous and to a lesser extent subjected to enzymatic degradation and neutralization of the liver. The action of hexamethylenetetramine and selenium in relation to stimulation of the body's cells.

Also of particular advantage is the fact that colloidal selenium is part of the metabolic chain of the body and are capable of binding to intracellular space. Thereby eliminated unwanted effects related to "dispose of" the body of the vehicle.

Bring the pH to 7.2 to 7.4 due to the need to create a stable system because of the acidity values above or below the specified limits will result in the destruction of the colloidal solution.

Selection process steps in the method due to the necessity of matching the task to be solved. The concentrations of the components ensure uniformity and stability and emission�STW.

Example 1.

Prepare 0.5 M solution se acid in distilled water. Prepare a mixture of se acid with polyethylene glycol 400 (hereinafter PEG 400), 250 μl of 0.5 M aqueous solution se acid insertion in 8 ml of PEG 400, vigorously stirred on a magnetic stirrer at 750 rpm, pH of this mixture and 7.55. Prepare a mixture of hydrochloric acid with hydrazine PEG 400, for this, 250 μl of 0.5 M aqueous solution of hydrazine hydrochloric acid insertion in 8 ml of PEG 400, vigorously stirred on a magnetic stirrer at 750 rpm, pH of this mixture to 0.68. With vigorous stirring is introduced into the solution se acid hydrazine solution dropwise. Put the resulting solution to dialysis against distilled water to remove PEG 400 and hydrazine hydrochloric acid. Excess water (in an amount equal to the amount of further insertion of hexamethylenetetramine) is distilled off on a rotary evaporator. In the resulting solution of hexamethylenetetramine is dissolved to a final concentration of 5%. The pH was adjusted to 7.2 to 7.4.

In total this means we get:

Hexamethylenetetramine - 0.05 g/ml;

Colloidal selenium - 0,00062 g/ml

As a percentage of the total volume of the composition of funds will be as follows, mass%:

Hexamethylenetetramine5
To�loigny selenium 0,062
Distilled waterTo 100

The means obtained by the proposed method, is a colloidal solution of selenium nanoparticles with adsorbed on its surface particles of hexamethylenetetramine.

Nanoparticles in drug was revealed by electron microscopy. The particle size is from 40 to 100 nm.

To solve this problem have been used cultures of human cancer cells HeLa, derived from cryo Bank cell culture collection of the Institute of Biochemistry and Physiology of plants and microorganisms, Russian Academy of Sciences. The cell culture was carried out in plastic flasks in complete RPMI medium (10% fetal serum, gentamicin, ampicillin, amphotericin b) at 37°C and 0.5% CO2. Dissociation of cells from monolayer culture was achieved by washing the monolayer with trypsin solution for 10 min. Number of cells 3·109in 1 ml.

The number of cells counted in the camera Goryaeva in 100 large squares grid Goryaeva and was calculated by the formula

X=a*250/100, i.e. X=a*2,5;

where X is the number of cells in 1 μl of cell suspension; a - the number of cells in 100 large squares. The number of cells counted is multiplied by 50. Ed. am. 106/ml.

To determine the activity of the cells used the MTT test. Conducting Mttest: pure culture of cells and the cells with the addition of drugs were incubated with 500 µl in Eppendorf tubes at 37°C for 48 hours. Each tube with the cell suspension after incubation centrifuged 10 min at 1000 g. Pererestorani the resulting pellet in 500 µl of MTT solution and incubated for one hour. After incubation the cells pererestorani in 500 µl DMSO, were selected in 200 μl of cell suspension from each tube and placed in the wells of 96-well flat-bottomed tablet. Readings of optical density was read at the reader at a wavelength of λ=490 nm.

To determine the parameters of acute toxicity of the test preparations when introduced into the stomach used nonlinear white mice.

White mice-males were kept in a vivarium according to sanitary rules and standard diet in accordance with the order of the USSR Ministry of health No. 1045-73 from 06.04.73 [24]; the good laboratory practices [23] and the USSR Ministry of health order No. 1179 from 10.10.83 [26] with the use of dry briquetted feed (LLC "Laboratorium", Moscow). The animals were housed in a vivarium under standard lighting conditions (12 h light/12 h darkness) at air temperature of 20°C and 70% relative humidity. Work with animals was conducted in accordance with the order of the USSR Ministry of health No. 755 from 12.08.77 G. [25] and rules adopted by the European Convention for the protection of vertebrate animals used for experimental and other scientific purposes.

Preparation for the experience of white mice was performed in accordance with the instructions of the CFC "Test toxicity� GF XI [21]. Acute toxicity was determined by the method of Kerber [22, 27].

Example 2.

A study on acute toxicity of funds obtained in example 1

Was taken 6 white nonlinear mice, male, weighing 15-20 g as a probe for drug injection was used insulin syringe with a soft tip of the catheter. Animals were introduced following volumes of the investigated tools:

1. Mouse No. 1 - 0.2 ml

2. Mouse No. 2 - 0.4 ml

3. Mouse No. 3 - 0.6 ml

4. Mouse No. 4 - 0.8 ml

5. Mouse No. 5 - 1.0 ml

6. Mouse No. 6 - 1.2 ml

Even reaching a dosage of 1.2 ml per head of the laboratory animal No. 6, we were unable to obtain the concentration of the funds received equal the LD 50 (the dose was 2 mg / kg). Immediately after the administration of funds in mice No. 3-6 were observed depression, impaired coordination of movement, refusal of food and water for 30 minutes. After the animal is stabilized. After 48 hours from the time of introduction it was noted that the remedy imposed 6 white nonlinear mice, did not cause the death of an animal.

Example 3.

Based on the above data, we have conducted basic research on acute toxicity. We have taken 4 groups of animals 6 animals each. The volume of administration of funds amounted to 0,6; 0,8; 1 and 1.2 ml per animal in each group respectively. Recalculation of the input volumes of fluids�TBA per 1 kg weight of the animal are presented in table 1.

The data in table 1 clearly show that when administered orally funds to mice at doses of 0.6-1.2 ml/kg it is not toxic to mice.

After the administration of funds in mice of all groups exhibited similar clinical picture, and in preliminary experiments, namely depression, impaired coordination of movement, refusal of food and water for 30 minutes. Then stabilized.

When observing animals within 7 days it was noted that the tool did not cause the death of an animal.

The introduction of a larger volume of liquid (more than 1.2 ml) animals not recommended in accordance with the provisions of the Pharmacopoeia, as this may cause damage to the digestive system or water intoxication in laboratory animals. Therefore, according to the data obtained oral remedy previously can be considered non-toxic.

Example 4.

The study of the interaction of the funds obtained in example 1, with the cell line HeLa

In our early studies, we found that when carrying out the incubation of cells for depleted and enriched environments for seven days, it was determined that in both cases their number is approximately the same (5·104cells/ml), indicators of respiratory activity were approximately equal, h�says about about the lack of influence of the composition of the nutrient medium on the properties of a population of cells of the HeLa line at low exposure.

In this case, when studying the respiratory activity of the cell line HeLa as 100% we adopted the optical density of the sample with the maximum amount of cellular material, when measured on a semi-automatic biochemical analyzer BS 3000 P Sinnova (China) at a wavelength of λ=492 nm.

At low concentration of cells, the amount of change in respiratory activity is at the level of the magnitude of analytical error of the method. Reasonably accurate results can be obtained using the analytical samples with cell counts of more than 15000 in 1 ml.

Preparation containing cell line HeLa, were resuspended in complete RPMI medium (with the inclusion of nourishing serum and antibiotics). The concentration of the drug, made on Wednesday, was 2 μg per 1 ml of medium.

In all experiments as control samples were used pure culture of cell line HeLa and cell lines HeLa incubated with selenium-containing solution. It was further determined the optimal time of incubation and identified the range of dilutions of selenium-containing means for subsequent studies. Cells were incubated with vehicle during the day. In table 2 and figure 1 presents the results of MTT assay on the respiratory activity of cell line HeLa (Se+Ge-selenium+hexamethylenetetramine (medium, obtained by PR�measure 1); Ge - hexamethylenetetramine; K - control).

After analyzing the data, it should be noted (table 2; figure 1) that observed the action as colloidal selenium, and hexamethylenetetramine. And hexamethylenetetramine increases the activity of cellular respiration is approximately 1.7 times, and the means obtained in example 1, increases the activity of cellular respiration approximately 2.4-fold, indicating a combined effect of both components on cellular respiration. The fact that the tool containing selenium and hexamethylenetetramine, even when diluted 10 times, have had a more pronounced positive effect on cellular respiration compared with the pure action of hexamethylenetetramine, pointed to the fact that the preferred effect on stimulation of cellular respiration provides the complex colloidal selenium and hexamethylenetetramine.

Thus, the means obtained by the proposed method, effectively to stimulate the body's cells.

The list of references

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2. Obukhova L. K. Chemical geroprotectors and the issue of increasing life expectancy // Uspekhi khimii. - 1975. - Vol. 44. - C. 1914-1925.

3. Frolkis, V. V., H. K. Muradyan Experimental way prodl�of life. - L.: Nauka, 1988. - 248 p.

4. Pharmacology of Aging Process. Methods of Assessment and Potential Interventions / Ed. by I. Zs-Nagy, D., Harman, K. Kitani. - Ann. N. Y. Acad. Sci. - 1994. - Vol.717. - 350 p.

5. Obukhova L. K., Emanuel N. M. Role of free-radical oxidation reactions in the molecular mechanisms of aging of living organisms // Uspekhi khimii. - 1983. - Vol. 52 Pp. 353-372.

6. Ames B. N., Shigenaga M. K., Hogen T. M. Oxidants, antioxidants, and the degenerative diseases of aging // Proc. Natl. Acad. Sci. USA. - 1993. - Vol.90. - P. 7915-7921.

7. Cutler R. Oxidative stress: its popential relevance to human disease and longevity determinants // Age. - 1995. - Vol.18. - P. 91-96.

8. Harman D. Free radical theory of aging: invreasing the functional life span // Ann. N. Y. Acad. Sci. - 1994. - Vol.717. - P. 1-15.

9. Papa S., Skulachev V. P. Reactive oxygen species, mitochondria, apoptosis and aging // Molec. Cell. Biochem. - 1997. - Vol.174. - P. 305-319.

10. Gusev V. A., Panchenko L. F. Modern concepts of free radical theories of aging // neurochemistry. - 1997. - T. 14. - P. 14-29.

11. Asok V. T., Ali R. The aging paradox: free radical theory of aging // Exp. Gerontol., 1999. - Vol.34.- P. 293-303

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13. Succinic acid in medicine, food industry, agriculture/ edited by M. N. Kondrashova, Y. G. Kaminsky, E. I. Maevsky. - Pushchino: ITBF wounds. - 1997. - 300 p.

14. Bjorksten J. Aging, primary mechanisms // Gerontologia. - 1963. - Vol.8. - P. 179-192.

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The method of obtaining funds for the stimulation of cells of the body, comprising preparing a mixture of 1 by adding 250 ál of 0.5 M aqueous solution se acid in 8 ml of PEG 400, intensive mixing on a magnetic stirrer at 750 rpm, pH of this mixture and 7.55, Yes�it is prepared a mixture of 2 by adding 250 µl of 0.5 M aqueous solution of hydrochloric acid hydrazine in 8 ml of PEG 400, intensive mixing on a magnetic stirrer at 750 rpm, pH of this mixture to 0.68, with vigorous stirring is introduced into the mixture 1 mixture 2 dropwise, the resulting solution was put on dialysis against distilled water, removing the PEG 400 and hydrazine hydrochloric acid, the excess water is distilled off on a rotary evaporator, the obtained solution was added hexamethylenetetramine, the pH was adjusted to 7.2 to 7.4, while the components are mixed in an amount that provides their content in the product, wt.%:

Hexamethylenetetramine5
Selenium0,062
Distilled waterTo 100



 

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6 dwg, 1 tbl

FIELD: process engineering.

SUBSTANCE: invention can be used for fabrication of super laminar blanks based on diverse materials. Initial blanks are composed of sheets of diverse metal alloys mutually soluble in the range of heating temperatures at hot forming. After cutting initial sheets to lengths, their surfaces are processed and cut sheets are stacked. At stacking, higher fusion point metal sheet is arranged between sheets of lower fusion point metal to make the barrier for crystallization in single ply depth to form a nano-sized structure. Sais stack is hot formed by heating and rolling at recrystallisation temperature corresponding to the lowest fusion point material. Said jobs are reiterated unless sandwiched sheet of produced with preset number of plies and depth.

EFFECT: sandwiched sheets produced without degassing.

FIELD: chemistry.

SUBSTANCE: invention relates to a process of formaldehyde removal by catalytic oxidizing which can be used in waste water treatment in petrochemical, medical, chemical and pharmaceutical industries. The process of formaldehyde removal from aqueous solutions at ambient temperature comprises exposing formaldehyde to a catalyst and oxidizing with oxygen. A nanocomposite material comprising silver - high basic anion exchanger in OH--form is used as a catalyst. The oxidation is conducted within 0.5-5 hours.

EFFECT: simple and cost-effective method for removal of up to 60-80% of the initial formaldehyde concentration in aqueous solutions at the temperature of T = 20-25°C and atmospheric pressure.

3 ex

FIELD: chemistry.

SUBSTANCE: carbon nanomaterials - nanotubes or graphene, particles of which contain hydroxyl and/or carboxyl groups on the surface are modified by treating with a solution containing triethanolamine titanate and fatty acid derivatives - triethanolamine stearate or triethanolamine palmitate. The molar ratio of said fatty acid derivative to titanium ranges from 1:1 to 3:1, and the weight ratio of said fatty acid derivative and titanium compounds with respect to titanium dioxide to nanotubes or graphene ranges from 0.75:1 to 2:1. The obtained suspension is treated with carbon dioxide gas until coagulation of the system and the precipitate is then washed with water.

EFFECT: obtained modified carbon nanomaterial disperses well in nonpolar media without using ultrasound.

2 cl, 1 tbl, 9 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine and can be used for the treatment of radiation-thermal injury of an organism. For this purpose a single subcutaneous introduction of bifidumbacterin, irradiated by gamma-rays in a dose of 14.0 Gy, is carried out. Bifidumbacterin is introduced in a dose of 1.43·106 CFU/kg. After that, 10% hypericum oil is applied on the burnt region. Then a 10% hypericum cream is applied after 3-4 days.

EFFECT: method makes it possible to carry out the treatment of combined radiation-thermal injuries in an effective way with the application of available and cheap pharmacotherapeutic means.

1 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: erythrocyte cell medium is added with an aqueous solution of sodium and potassium salts of humic acids prepared on brown coal of leonardite in a dose of 10.0 mg/kg. That is incubated at a temperature of 37°C for 40 minutes before treatment with acidic haemolytic.

EFFECT: invention enables normalising the cell membrane permeability and reducing the damaged cell count under acidic haemolytic.

1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a new intensifier of the antitumour effect, which is a uracil derivative of the general formula (I) or its pharmaceutically acceptable salt. In the general formula (I) X represents a C1-5-alkylene group, and wherein one of methylene groups making an alkylene group is optionally substituted by an oxygen atom; R1 represents a hydrogen atom or a C1-6-alkyl group; R2 represents a hydrogen atom or a halogen atom; and R3 represents a C1-6-alkyl group, C2-6-alkenyl group, C3-6-cycloalkyl group, (C3-6-cycloalkyl)-C1-6-alkyl group, halogen-C1-6-alkyl group or a 5-6-merous saturated heterocyclic group with an oxygen atom as a heteroatom, a uracil derivative presented by the following formula (I). The invention also refers to a method for potentiating the antitumour action or a method of treating tumours, involving administering an effective amount of a combination of the above uracil derivative or its pharmaceutically acceptable salt and an antimetabolite in an effective amount. The antimetabolite represents an agent specified in 5-fluoruracil (5-FU), potassium tegafur/gimeracil/oteracil (TS-1), tegafur/uracil (UFT), capecitabin, 5-fluor-2'-deoxyuridine (FdUrd) and Pemetrexed.

EFFECT: preparing the intensifier of the antitumour effect.

18 cl, 10 dwg, 10 tbl, 67 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to methods of purification and health improvement of an organism. For this purpose therapeutic starvation for not fewer than 5 days in case of a 7-day programme and for not fewer than 7 days in case of a 9-day programme is carried out. The duration of a recovery period constitutes two days. Food intake is realised nine times per day each day both in the process of therapeutic starvation and in the recovery period. In the period of therapeutic starvation the first food intake includes bee products "APIGRANULES 2" in a dose of one teaspoon, "KHINAZI balm" in a dose of one teaspoon, "A-P-V" in a dose of one teaspoon, "APITOK" in a dose of one teaspoon, "Antihelm phyto" - one capsule and still mineral water - one glass. The second food intake includes a drink with ginger, lemon juice, garlic and mint, honey - one teaspoon and one glass of apple-carrot juice. The third food intake supposes an intake of bee products "APIGRANULES 2" in a dose of one teaspoon, "KHINAZI balm" in a dose of one teaspoon, "A-P-V" in a dose of one teaspoon, "Antihelm phyto" - one capsule and still mineral water - one glass. The fourth food intake includes a drink with ginger, lemon juice, garlic and mint, honey - one teaspoon and one glass of apple-carrot juice. The fifth food intake consists of tea black or green with ginger, one teaspoon of honey and one glass of apple-carrot juice. The sixth food intake consists of bee products "APIGRANULES 2" in a dose of one teaspoon, "A-P-V" in a dose of one teaspoon, "Antihelm phyto" - one capsule and one glass of still mineral water. The seventh food intake includes tea black or green with ginger, one teaspoon of honey and one glass of apple-carrot juice. The eighth food intake supposes an intake of tea black or green with ginger, one teaspoon of honey and one glass of apple-carrot juice. The ninth intake of food includes depressant tea, including mint grass, valerian root, fennel seeds, cumin seeds, epilobium or strawberry leaves and one glass of apple-carrot juice. In the recovery period in 1-st, 2-nd, 3-rd, 4-th and 6-th intakes of food the composition of products remains the same as in the process of starvation. For the fifth intake of food the patients take tea black or green with ginger, one teaspoon of honey and vegetable soup. For the seventh intake of food the patients take tea black or green with ginger, "MILK COCKTAIL WITH CHITOSAN". The eighth intake of food includes tea black or green with ginger, one teaspoon of honey, "APICAMPA" cereal. The ninth intake of food for the recovery period includes a baked apple, depressant tea. In addition, a number of procedures are carried out after each food intake during the period of therapeutic starvation and the recovery period. After the first food intake gymnastics "5 Tibetan pearls" is realised. After the second food intake exercises on training apparatuses, procedures of press-therapy, electrolypolysis and myostimulation are realised. After the third food intake exercises of therapeutic physical training or aerobics are performed. After the fourth food intake a rest in form of a walk, a halotherapy session, combined with a session of relaxation therapy are realised. After the fifth food intake a course of strip-plastic is carried out. After the sixth food intake massage by manual application with a peloid-based mixture or manual massage with honey is carried out. After the seventh food intake an infra-red sauna, shower, phytobath with medicinal herbs, honey, ginger, lemon juice is taken. After the eighth food intake a shower is taken.

EFFECT: method ensures effective health improvement of the organism with the preservation of the full value life style and a sense of a comfortable state in the starvation period, reduction of recovery period term after starvation, purification of the organism without loading on the gastrointestinal tract, weight loss, and improvement of the general state and workability of the patients.

3 tbl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to biotechnology, specifically to a fused protein containing a variant of rodostomin, and can be used in medicine. An ανβ3 integrin selective polypeptide consisting of an amino acid sequence SEQ ID NO:1 conjugated on the N terminal by a linker amino acid sequence containing a combination of the amino acids glycine and serine with a variant of a human serum albumin (HSA) with SEQ ID NO:4.

EFFECT: invention enables the higher therapeutic effectiveness in the diseases related to ανβ3 integrin.

12 cl, 14 dwg, 2 tbl, 7 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine and can be used for the correction of the individual's functional state and performance. That is ensured by administering Semax neuroactive peptide in a dose of two drops in each nasal passage. That is followed by the electric current exposure covering a frontal-mastoid region at pulse length 0.2ms, current intensity 0.8mA and pulse train 800Hz for 40 min. The exposure is combined with at least 10 sessions of hyperbaric oxygenation at pressure 1.6 atm.

EFFECT: method provides the rapid and effective increase of performance in sportsmen, military men and individuals involved in the other professions related to significant physical and mental stress by improving the functions of various regions of brain cortex as a result of the selected complex exposure enabling the substantial vasodilatation and maximum tissue oxygenation.

1 tbl

FIELD: medicine.

SUBSTANCE: using a compound representing a bicyclic pyrimidine derivative as Hrf2 transcription factor activators.

EFFECT: compounds of general formula can be used preventively to increase body defences before operations with toxic chemicals and high radiation doses.

3 cl, 7 tbl, 11 ex, 9 dwg

FIELD: medicine.

SUBSTANCE: invention refers to methods for cell and tissue protection against a hypoxic injury and can be used for developing remedies for hypoxic and ischemic injuries. The developed method for protection is based on cell treatment by substances increasing a level of glutathionylation of Na,K-adenosine triphosphatase catalytic subunit that reduces to its activation. The obtained results can be actual for biological research institutions, medical facilities, particularly cardiologic clinics, as well as biotechnological companies for transplantology and tissue engineering.

EFFECT: presented method can be used for research activities aiming at creating the therapeutic agents for relieving tissue injuries, particularly myocardial tissue in hypoxia and hypoxia/reoxygenation.

6 dwg

FIELD: sports.

SUBSTANCE: invention relates to sports medicine and pharmacology, and can be used to increase the overall physical performance of athletes of speed and power sports. To do this, the dietary supplement "Epsorin" is added daily twice a day. At that during the stage of physical training "Epsorin" is taken in for two weeks 30-40 minutes prior to start of the exercise-training process as 10-15 drops per a glass of water; during the period of special physical training it is taken for 10 days 30-40 minutes prior to start of the exercise-training process as 10-15 drops per a glass of water; during the transition period it is taken for 3-5 days 30-40 minutes prior to the training as 5-7 drops per a glass of water; on the day of competitions the dose is increased to 20-30 drops per a glass of water.

EFFECT: method enables to improve the overall physical performance and endurance of athletes due to activation of metabolism and antioxidant systems of the body.

1 tbl

FIELD: medicine.

SUBSTANCE: as an ingredient of drinking water or beverage, water containing 1H16OD isotopologue in an amount from 0.0002 to 0.0278 molecular %. The invention provides higher individual's body resistance to the flight factors, such as: height gain, cabin and compartment noise increase, vibration, rolling, humidity disposal, time zone change.

EFFECT: higher resistance of the mammalian body to the effect of the flight factors on an aircraft.

2 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: method for producing an agent inhibitory the tumour cell growth, involving preparing a mixture of aqueous solution of selenious acid and PEG 400; that is followed by preparing a mixture of aqueous solution of hydrazine hydrochloride and PEG 400; the produced mixtures are combined; the solution is put to dialyse against distilled water; surplus of water is driven off in a rotary evaporator; the produced solution is added with silymarin dissolved in Solufor with dialysis against distilled water; pH is reduced to 7.2-7.4; the method is implemented in certain circumstances.

EFFECT: agent produced by the given method possesses high inhibitory action on the tumour cell growth.

4 dwg, 2 tbl, 2 ex

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