Drug possessing antihypoxic, actoprotective, nootropic activities and having effect on physical efficiency, and based pharmaceutical composition

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmacology and medicine and concerns the use of dihydrobromide 9-(2-diethylaminoethyl)-2-(3,4-dioxyphenyl)imidazo[1,2-a]benzimidazole of formula as a biologically active compound possessing high antihypoxic, actoprotective, nootropic activities and having a positive effect on physical efficiency, and a based pharmaceutical composition.

EFFECT: preparing the compound possessing high antihypoxic, actoprotective, nootropic activities and having a positive effect on physical efficiency, and the based pharmaceutical composition.

2 cl, 8 tbl, 3 ex

 

The invention relates to pharmacology, namely to biologically active substances with antihypoxic, act-protective and nootropic activities and positive effect on physical performance, which can be used to create medicines for the treatment of hypoxic conditions of different Genesis, improve efficiency, treatment of cognitive disorders.

Hypoxia is a typical pathological process, complicating the course of various diseases of infectious and non-infectious nature [Ivekovi, Navdata and other Modern approaches to pharmacological correction of hypoxic States // Sports medicine. - 2008. No. 1. - P.36-41]. Despite the differences in the initiating mechanisms of development of hypoxia in certain pathologies, leading to disorders of systemic hemodynamics, regional blood flow, microcirculation, changes in the qualitative and quantitative composition of the blood, the enzyme activity of tissue respiration, resulting metabolic shift during hypoxia is the lack of redox processes and the supply of tissues [Ldeucom. The signal function of mitochondria during hypoxia and adaptation // Pathogenesis. - 2008. No. 3. - P.4-12].

As is known, the characteristic features of hypoxic syndrome are the two who are excessive accumulation of intermediate metabolites of glycolysis, lipolysis, proteolysis, the development of a metabolic acidosis with subsequent secondary nonspecific metabolic and functional disorders that exacerbate the underlying disease course. Under the influence of an excess of hydrogen ions in hypoxia occurs to increase the permeability of lysosomal membranes and, consequently, the development of destructive processes in the tissues under the influence of lysosomal hydrolases. Last initiate the formation of eicosanoids and prostanoids in the process of mutual transformation giving rise to free radicals (SRS) [Menushenkov, Megamasso, Nposhnikov. Metabolic effects of antioxidants in acute hypoxic hypoxia. // Basic research. - 2006. No. 1. - P.17-21]

Cause excessive formation of CF during hypoxia may be a blockade of the final link of the respiratory chain in mitochondria, the electron leakage on the way to the cytochrome oxidase, which leads to a one-electron reduction of oxygen with the formation of its active forms. It is known that hypoxia increases the transformation antiaging in the xanthine oxidase, initiating the formation of superoxide anion radical. At the same time, activation of sympathoadrenal system observed during hypoxia of different Genesis, also accompanied by increased education Akti is the major reactive oxygen species (ROS) when autookislenia adrenaline [Nposhnikov, Megamasso, etc.. Activation processes lipoperoxidative - efferent link disintegration of cellular structures in acute hypoxic hypoxia // Successes of modern natural science. - 2007. No. 7. - P.42-45].

For the correction of hypoxic conditions used antihypoxants, such as gutimin [Everuone, Pdelab Molecular pharmacology antihypoxants. // SPB.:LLC "Publishing house H-L", 2004. - 368 S.] however, as one of the reference antihypoxants in the experiment, gutimin has not found wide clinical application.

Thus, one of the main parts of the system functional and metabolic disorders in hypoxic States is the activation of free radical processes (PSA) and, in particular, lipid peroxidation. In this regard, the obvious importance of the use of antioxidant agents in hypoxic injury [Art, Antioxidants and antihypoxants in obstetrics (oxidative stress in obstetrics and therapy antioxidants antigipoksantami) - SPb.: Dehaene, 2001. - 400 C.].

The problem of improving health has become particularly acute in recent years due to the rapid scientific and technical progress. Along with physical training, mental autogenic training, meditation, physiotherapy promising methods is the development of lcars the drugs, enhancing human performance [Bobkov YG, V.M. Vinogradov, Rollers V.F., S. Losev, A.V. Smirnov Pharmacological correction of fatigue // M - Medicine. - 1984. - 208 S.; Smirnov, A.V. Psychomotor stimulants as a means of improving health. // Pharmacol. and toxicol. - 1990. No. 4. - P.72-77; Morozov I.S. New directions of drugs with increasing human efficiency in extreme conditions and activities // Ross. the scientific. Conf.: Antihypoxants and Ecoprotection: Results and prospects. - Saint-Petersburg, 1994. - VIP. - S].

Currently, the problem of the creation and use of medicines to improve the health of the person being mainly in the framework of the pharmacology of a healthy person and are of special interest for sports, military and space medicine [Redsamara. Use of drugs by healthy people. Experimental and clinical pharmacology. - 1994. No. 3. - P.3-7]. It is not envisaged treatment of patients, and the use of pharmacological agents is more of a preventive nature, helping to overcome stress and overstrain of the Central and peripheral nervous system, functions of the locomotor apparatus, systems and organs.

In addition, this problem has a purely clinical aspect. He Zack is udaetsya is in modern clinical medicine increasing importance given to the rehabilitation areas. To return to the patient the ability to work, to improve his performance, at least with the aim of self-service is a very important challenge for physicians in rehabilitation period after myocardial infarction, stroke, severe infections or surgical interventions [ei Chazov. Focal degeneration and necrosis of the myocardium (myocardial infarction) // Manual of cardiology in 4 volumes. - M.: Medicine. - 1982. - V.3. 49 - 107; Charles, VA Therapy for neurological diseases: Guide for physicians) - M.:Medicine. - 1987. - 512 S.]. It was repeatedly noted that improving the health of the patient, expressed in the increase of physical activity is a key moment in its psychological and social rehabilitation [Headacke. Overcoming hypokinesia. // In the book. Preventive cardiology: a Manual. - M.:Medicine. - 1987. - S.401-415]. Undoubtedly the application in this direction drugs that increase efficiency, has plenty of great prospects. One of the famous Ecoprotection is a derivative of benzimidazole - bemythyl [Everuone, Pdelab. Molecular pharmacology antihypoxants. // SPB.:LLC "Publishing house H-L", 2004. - 368 S.].

To improve performance of frequently used Ecoprotection, n is the most famous of these is a derivative of benzimidazole - drug bemythyl. Ecoprotection not only improve efficiency, but also represent a group of drugs having the property to normalize and improve the disturbed functions of the body, caused by pathological processes and stress exposure.

The development of modern Ecoprotection is based on the concept of limiting the efficiency levels of the metabolism. It is obvious that the main trigger negative factors, resulting in reduced efficiency and the development of fatigue are lack of oxygen (working hypoxia)combined with lack of energy substrates, as creatine phosphate, glycogen and accumulation of oxidized products (lactate), leading to the development of acidosis [Thal L.J., Grundman M, Berg J., Ernstrom K, et al. Idebenone treatment fails to slow cognitive decline in Alzheimer's disease. // Neurology. 2003 Dec 9; 61(11): 1498-502; Vollestad N., Blom, P., Effect of varying exercise intensity on glycogen depletion in human muscle fibres // Acta Phisiol. Scand. - 1985. - V.125. No. 3. - P.395-405]. The stress on the background of the lack of oxygen leads to an abrupt activation of free radical processes that lead to changes in the biophysical properties of membranes and, consequently, to decreased activity of membrane-bound enzymes, which leads to violation of energy supply and, ultimately, limits the performance. This hypothesis is odvodit fundamental basis under relatively successful use of antioxidants in sports medicine [Meyerson FS Pathogenesis and prevention of stress and ischemic injury of the heart // M, Medicine, 1984. - 272 S.; Seyfulla RD, Borisov I.G. Poblems pharmacology of anti-oxidants. // Pharmacology and toxicology. - 1990. - T. No. 6. - P.3-10]. Own antioxidant radical scavenging activity of existing Ecoprotection, such as bemythyl, expressed weakly [MB carpenters, Kobzeva E.A., Plotnikova T.M. Antioxidant effects of antihypoxants ischemia of the brain, Byull. exp. Biol. The honey. - 1992. - T, No. 5. - S-506].

All this makes the actual research on the impact of new antioxidant substances exhibiting act-protective properties, physical performance and recovery.

Impaired memory and learning ability is accompanied by a number of diseases and injuries of the Central nervous system, but is most common in dementia of various etiologies. Usually the term dementia understand is not a disease but a syndrome represents a constellation of symptoms that can cause cognitive disorders and memory impairment. These include violations of orientation disorder of attention, difficulty speaking and slow reactions. Dementia involves a progressive decline of cognitive abilities beyond normal age-related changes [Witmer R. Alzheimer's Disease, dementia and diabetes - what's the link? Dabetes Voice, 2008, 53 (3), S 19-22]. Causes of dementia along with neurodegenerative and vascular diseases can be alcohol, drugs, endocrine diseases, infections affecting the brain tissue, encephalopathy of various origins [Lehmann-horn F., Aludel. Treatment of diseases of the nervous system. M: Medpress-inform, 2009. - 528 S.]. Proven role of stress in the development of mental disorders [Each So, G.B. Stefano, Fricchione G.L., Benson H. The role of stress in neurodegenerative diseases and mental disorders. Neuro Endocrinol Latt. 2002 23 (3), 199-208]. Among the risk factors associated with development of dementia, note the presence of abdominal obesity is already at a Mature age (40-45 years), decreased physical activity and lack of dietary unsaturated fats, vitamins C, E, b6B12and folic acid [Roitman, 2008]. In 2005 there were 24.3 million persons suffering from dementia and annually additional 4.6 million new cases [Iwillhall, Gaussain, Sigavrilova. Cholinergic therapy for Alzheimer's disease and its impact on health and quality of life of caregivers violence. // Journal of neurology and psychiatry. Saw. - 2010. - T.110. No. 5. - Pp.33-38].

In General, the population of the world start to age faster, estimates suggest that the increase in the total number of people with cognitive disorders over the next 25 years. is traditionally the attention of neurologists given sensitive motor and visual disturbances as the most obvious and disabling and the study of neuropsychological status plays a minor role [Cosmescu, Ividually. Memory disorder in multiple sclerosis. // Journal of neurology and psychiatry. CSV, 2010. - T.110. No. 9. - P.8-13]. Despite this disruption of cognitive functions is a serious problem, since it entails the loss of professional suitability, social and psychological maladjustment patients, impairs their quality of life [Ayuamarca, Navratalova, Mealhouse. The influence of sulfate amantadine on cognitive impairment in patients with Parkinson's disease. // Journal of neurology and psychiatry. Saw. - 2010. - C, No. 7. - P.24-30].

Dementia is a problem not only patients, but their family members caring for patients. The increase in the number of such patients will be in the coming years becomes an even bigger burden for public health services [Kolykhalov IV, 2010]. Due to the above facts, the search means possessing the ability to eliminate the memory bottleneck, to restore learning ability, thinking and to improve the intellectual abilities in various diseases and in healthy individuals, is certainly relevant. Traditionally, this purpose prescribed drugs with neuroprotective activity. As defined by the world Health Organization is storing to a group of nootropic drugs include medicines, capable of directly activating influence on the processes of learning, improve memory and mental activity, as well as improve brain resistance to corrosive influences.

About the extreme importance of the drugs with neuroprotective activity data about the wide spread of their application. According to who statistics, one third of the adult population in Europe and Japan used nootropics, and with good reason can be attributed to the group of essential drugs [Weaken, Casareyna. Range of pharmacological effects of Phenotropil // Farmateka, 2005. No. 13 (108). - P.19-25]. To date, several distinct groups of drugs with neuroprotective activity, among which monoaminergic stimulants, chainposition substances glutamatergic drugs, neuropeptides, substance, affecting the excitatory amino acids and other [Ostrovskaya RU Modern strategies of cognitive impairment. // Materials of the V International conference "Biological basis of individual sensitivity to psychotropic drugs". Moscow. - 2010. - P.6]. It is known that among a group of drugs that have the potential to impact cognitive function and neuroprotection, there is a group of antioxidant agents presented in this preparation, as, for example, Mexidol [Vajrayana. Features and mechanism neuropro cornago steps of Mexidol in the hemorrhagic stroke in the experiment. // Bulletin of experimental biology and medicine. - 2006, Annex 1.; Niescierenko, Laurasia, Twhbea, Nusaybin, Wiimusic. The effectiveness of Mexidol in experimental cerebral ischemia. // Bulletin of experimental biology and medicine. - 2006, Annex 1.; Wepman, Nuvolini, Maharatna. The effectiveness of cardioprotector the Mexicor in the complex therapy of patients with acute cerebral blood circulation on the background of arterial hypertension. // Angiology and vascular surgery. - 2008. - T, No. 4. - S.43-48]. However, the antioxidant activity of Mexidol on previously obtained data [Vahasalo, Spa, VAIDISOVA. The study of the antiradical activity of the new compounds by chemiluminescence // Biomedical chemistry. - 2005. - C, No. 3. - Page 287-294] is negligible, which makes the actual search for new substances with neuroprotective and antioxidant properties.

The technical result of the invention is to improve antihypoxic, act-protective and nootropic activities and positive impact on physical performance.

The technical result is achieved by using dihydrobromide 9-(2-diethylaminoethyl)-2-(3,4-dioksifenil)imidazo[1,2-a]benzimidazole of the formula I

as a means of having antihypoxic, AK is protectores, nootropic activity and positive impact on physical performance.

The technical result is also achieved by a composition comprising as an active start dihydrobromide 9-(2-diethylaminoethyl)-2-(3,4-dioksifenil)imidazo[1,2-a]benzimidazole of the formula I:

taken in an effective amount.

Dihydrobromide 9-(2-diethylaminoethyl)-2-(3,4-dioksifenil)imidazo-[1,2-a]benzimidazole of the formula I is known as biologically active compound exhibiting antioxidant properties (Kosolapov, VA, Spasov AA, Anisimov, V.A. study of the antiradical activity of the new compounds by chemiluminescence. Biomedical chemistry, 2005, t, No. 3, page 287-294; Anisimov, VA, Spasov AA, Kosolapov, VA and other Synthesis and biological activity of 9-dialkylaminomethyl-2-hydroxy(deoxy)-phenylimidazo[1,2-a] benzimidazole. Chem.-farmgirl, 2006, t, No. 10, p.3-10).

Compound I is also cerebroprotective effect in radiation damage (Vereshchagin VK, Spasov AA, Anisimov, VA, Sanchakou I.D. Derived imidazo[1,2-a]benzimidazole - tool, providing cerebroprotective effect in radiation damage. Pat. Of the Russian Federation No. 2238938 (2004)).

The compounds I are also detected anti-ischemic, hemorheological and antiradical properties (Anisimov, VA, Kosolapov, VA, Minkin V.I. and other Digi rebraid 2-(3,4-dihydroxyphenyl)-9-diethylaminoethylamine[1,2-a]benzimidazole and pharmaceutical composition based on it. RF patent №2391979 (2010)).

In a series of salts of 9-(2-diethylaminoethyl)-2-(3,4-dioksifenil)imidazo[1,2-a]benzimidazole no known connection with antihypoxic, act-protective and nootropic activities and positive impact on physical performance.

Ways of getting dihydrobromide 2-(3,4-dioksifenil)-9-diethyl-aminoethylamide[1,2-a]benzimidazole I described in the above articles and patents and is the condensation of 1-diethylaminoethyl-2-aminobenzimidazole with 3,4-dimethoxyphenethylamine or 3,4-dioksifenilalanina, subsequent cyclization of the resulting condensation halides 1-diethylaminoethyl-3-(3,4-dimethoxy(3,4-dihydroxy)phenacyl)-2-aminobenzimidazole in 48%Hydrobromic acid (TKIP°C), resulting in the desired product I.

Below are the materials, methods and results of studies of the compounds I.

Experiments were performed on 416 white weinbrenner mice of both sexes weighing 18-22 g and 138 nonlinear white rats-males weighing 170-300, the Animals were kept on a standard diet in vivarium conditions (temperature 22-24°C, relative humidity of 40-50%) on a standard diet with observance of all rules and International recommendations of the European Convention for the protection of vertebrate animals used in experimental research (1997). IOM is NT experiments the animals were healthy, changes in behavior, appetite, sleep and wakefulness were not found.

1. Antihypoxic activity

Antihypoxic activity was studied on the model of hypoxia of different Genesis: acute hypobaric and gistologicheskoe hypoxia. As the comparison drug was selected antihypoxic drug gutimin [Lavastuseks. The main methods of assessment protective actions antihypoxants in the experiment and their influence on metabolic processes in the cell. Pharm. correction of hypoxic States: Sat. scient. Tr., The Institute of pharmacology RAMS, M., 1989, pp.118-124]. The study tool was administered intragastrically 1 hour before the start of the experiment. The control group received solvent in the same amount.

Modeling of acute hypobaric hypoxia (AGBG), which is based on the decrease in Rho2in the air we breathe while reducing the overall partial pressure, was performed on weinbrenner mice in a flow chamber at a temperature of 20-22°C (Methodical recommendations for a pilot study of drugs proposed for clinical studies as antihypoxic funds: Method. Ed. Ludlowkoeni. - M., 1990. - 18 C.). The testing was performed under the vacuum atmosphere, causing the death of animals, which for mice was 170-186 mm Hg, which roughly corresponds to the height of 11000 metro is. Recorded life time (TW, min) on "death ground" from the moment you rise to "pad" until the second agonal breath or death. The effectiveness of antihypoxic properties were evaluated by the protection factor (KC), calculated according to the change of TWexperimental animals at the "height" relative to TWcontrol:

To simulate acute gistologicheskoe hypoxia (AGTG), which is a consequence of the inactivation of cytochrome C oxidase, the enzyme terminal segment of the respiratory chain, used potassium cyanide at a dose of 9 mg/kg (LD100) [Mwikali, Philonenko. Antihypoxic funds. // Minsk.: Belarus, 1976, 128 S.], which was introduced weinbrenner mice intraperitoneally once. Calculations of the effectiveness of the drugs produced survival rates (W, %).

The connection I on the model of hypobaric hypoxia showed a pronounced protective effect, excelling in a dose of 5 mg/kg of the drug comparison gutimin activity (table 1), increasing the lifespan of mice.

Table 1
The influence of the studied substances on the lifetime of animals in acute hypobaric hypoxia (M±m)/td>
The group of animalsDose, mg/kgLife time (TJ), s (M±m)The protection factor
Control-60,0±3,1-
The connection I5,082,5±3,21,38
10,071,2±3,81,19
Control-46,6±2,4-
Gutimin10,060,0±1,8+1,29
the number of mice in each group=10
- differences are significant (q') compared with controls (p≤0,05)
+the drug was administered three times oseltamivir

Model gistologicheskoe hypoxia connection I began to act in a dose of 0.5 mg/kg and increasing the dose to 5 mg/kg protective effect of the composition is l 100% (table 2). Drug comparison gutimin showed moderate activity, yielding compound I in the whole range of studied concentrations. This high activity of compound I on the model of tissue hypoxia may be useful in cases involving local disruption or blockage of the respiratory chain.

Table 2
The influence of the studied substances on the survival of animals in acute gistologicheskoe hypoxia, (M±m)
The group of animalsDose, mg/kgThe number of survivorsSurvival, %
Control-0-
RU-1850,5440,0
1,0880,0∗∗
5,010100,0∗∗
Control -0-
Gutimin10,000,0
20,0330,0
50,0220,0
the number of mice in each group=10
InWthe survival rate of mice
- differences are significant (Fischer method) compared with controls (p≤0,01)
∗∗- differences are significant (Fischer method) compared with controls (p≤0,001)

2. Impact on physical performance and act-protective activity

The effect of compound I on physical performance was investigated in the following series of research:

- the effects of substances in a single intragastric introduction on physical performance of mice in the test voyage to the limit with load of 5% of body mass;

- the effects of substances in a single intragastric introduction on physical performance of mice in the test speed p is avania.

Act-protective activity was studied on the model of swimming in antiorthostatic position in hypoxia.

Drug comparison served actoprotector bemythyl.

In experiment took animals that did not show in the pre-test is a 15-minute swim with the burden of 5% of body weight - obvious signs of fatigue. The physical health of the animals studied in the swimming test method [Melnikova. Research methods the chronic action of harmful factors of the environment in the experiment. L., 1964]. Swimming animals was carried out in a vessel with a diameter of 1.5 m, filled with water (water temperature 28-32°C) up to level 60 see the Cargo weight was 5% of the body weight of animals. Indicator physical exhaustion of the animal was its finding under water for more than 10 seconds. The effectiveness of the substances was evaluated by increasing the duration of the voyage experimental groups of animals compared to control groups.

The effects of substances on the rate of development of fatigue was studied by the method of Kiplinger (G.L. Kiplinger. The Effects of Drugs on the Rate of Development on Fatigue in mice. Texas Rep. Biol. Med., 1967, vol.25, p.531-540). This test has certain advantages when studying the effect of substances on performance over other swimming techniques (Ugoku, Vminor, Vphoto, Soi, A.V. Smirnov. Pharmacological correction of fatigue // M.: Medicine, 1984, 208 S.).

Experiments pollalis in mice in a metal vessel size HH see Pre-mice coached: 48 and 24 h before the experiment mice swam fixed distance of 150 cm 5 swims 3 times with 30-minute breaks between groups of races. While mice developed persistent reflex sailing in the right direction to get out of the water by the ladder. On the day of the experience mouse did 18 continuous swim, time and expected speed of development of fatigue. In that case, if the mouse has covered the distance in 60 sec or more, it was excluded from further races and time further attempts was taken as equal to 60 seconds. The results of the experiment were processed using linear regression analysis. The effectiveness of the drug is characterized by a tg value of the α angle of inclination of the regression line, which is less than the drugs effectively prevent the development of fatigue.

The tested substance was administered in the dose range of 1-50 mg/kg in two ways - intragastric and intraperitoneal. The substance was administered, as a rule, when it is not the aim was to clarify the dynamics of the effect in time, 1 hour before the experiment. For injection used aqueous solutions of compound I and bemythyl.

Performance in antiorthostatic position was investigated by the method (Omegaman., Aaasian. A new model of dynamic work in small laboratory animals. Bull. exp. Biol. honey.. - 1977. No. 9. - S-559) the modification Gavia with TCS. (Gavle, Spa, Overstroke, Avibase. The effect of pharmacological substances on performance under conditions of moderate hypoxia. The results of science and technology, Serverpackage, Chemotherapeutic drugs, v.27, Antihypoxants, M.: VINITI.. - 1991. - S-127). Rats were fixed by the tail plate using a vacuum hose so that the head and neck of the animals were immersed in water. This situation forced the animals to keep his head above water surface using a dynamic (Gribkova movement of the front legs) and static (the muscles of the trunk). The intensity and duration of activity of rats was controlled by means of the goods (8% of body mass), fixed on the neck of animals. The effects of substances on the performance was studied as in normoglycemic and hypobaric hypoxic conditions [Kovalev and others, 1991], which was modeled in the flow chamber, the atmospheric pressure was 462 mm Hg, RO2=97 mm Hg, which corresponds to an altitude of 4000 m above sea level. As follows from the presented data (table 3), the connection I had act-protective action in the swimming test, improving the health of animals. For it was characterized by the appearance of the effect at a dose of 1 mg/kg, then 5 mg/kg to maximum effect and further reduction of the effect with increasing dose. Drug comparison bemythyl on this model turned out to be the Xia ineffective.

In the study of the effectiveness of the substances in the test on the speed of development of fatigue [Kiplinger, 1967], it was found that compound I at doses of 10 and 25 mg/kg significantly reduced the signs of development of fatigue in mice (table 4). The maximum effect of a substance expressed in a dose of 25 mg/kg In this model is very effective proved to drug comparison bemythyl, which is consistent with literature data [Bobkov and others, 1984]. He reduced the coefficient on x (tgα) 3 times. In this connection I, reducing signs of fatigue in mice to a greater extent than the bemythyl, had a more pronounced effect.

Comparing health data in normoglycemic and hypoxic conditions (table 5), it should be noted that the effect of compound I in both cases was about the same. In contrast, the efficacy comparison bemythyl decreased significantly when hypobaria. So, bemythyl completely changed the voyage rats at the “height” of 4,000 meters

Table 3
The effect of compounds I and bemythyl after intragastric administration 1 hour before the experiment on the physical performance of mice (n=10) (swimming with load of 5% of body weight)
The group of animalsD is for, mg/kgThe duration of swimming animals in minutes (M±M)Δ% of control
Control-23,5±1,1-
The connection I129,1±0,923,8
542,1±1,979,1
1030,8±2,931,0
2034,5±2,546,8
5024,8±2,65,5
Control25,1±1,0-
The bemythyl126,1±2,43,2
1022,8±3,6-10,2
2024,5±3,4-3,4
5024,8±4,02,2
- the differences are statistically significant compared to control (P≤0,05)
n - number of animals

/tr>
Table 4
The effect of compound I and bemythyl on the rate of development of fatigue mice (n=10) in the test of high-speed sailing
The group of animalsDose, mg/kgA linear regression equation
control+matter
The connection I5y=0,h+14,6y=0,14+10,1∗∗
10y=0,h+14,6y=0,12x+7,3∗∗
25y=0,h+10,9y=0,h+10,8∗∗
The bemythyl5y=0,h+14,6y=0,16x+13,9
10y=0,h+14,6y=0,11X+9,0∗∗
25y=0,h+14,6y=0,h+9,9∗∗
- u - the average time sailing in min X100
x - squared average attempts
∗∗- the difference is significant (p<0,05) according to two-factor analysis of variance

Table 5
The influence of the studied substances after intragastric administration on exercise performance of rats (n=12) during normal and low oxygen content (97 mm Hg) when swimming in antiorthostatic position with cargo 8% of body weight
Dose, mg/kgThe length of the voyage in normoglycemic conditions (min)The duration of the plan the project in hypoxic conditions (min)
Substance
Control (M±m)Experience (M±m)Control (M±m)Experience (M±m)
The connection I1010,5±1,515,8±1,76,5±0,46,6±0,3
2010,5±1,517,3±1,36,5±0,49,1±0,4
5010,5±1,517,5±2,06,5±0,49,0±0,4
The bemythyl5010,5±0,214,5±0,4∗6,5±0,26,7±0,4
data are statistically significant (p<0,05) compared to the control
n - number of animals

3. Nootropic properties

Nootropic activity was studied on the influence of substances on the formation and playback is the introduction of memorable track using the methods of the conditioned reflex of passive avoidance (passive avoidance reaction) [Aburish, Aborisova, Dphoto. Techniques and basic experiments for the study of brain and behavior. TRANS. from English. Angiopatiei. M.: Vysshaya SHKOLA, 1991, 399 S.].

The method of the conditioned reflex of passive avoidance based on the suppression of innate reflex preference dark space available to the rodents. The experimental setup consists of a camera, consisting of two compartments: a large - lit and small - dark. The animal is placed in the bright compartment and soon (10-20 sec), due to innate reflex preference dark space, moves into a small compartment, after which the door connecting the two compartments, overlaps and on the floor of the dark compartment, consisting of parallel stripe electrodes, electrical current pulses with a duration of 50 MS, a frequency of 5 Hz and an amplitude of 50 mA. After 10 seconds the door opened and the animal can pop out in the bright compartment with a conventional floor. In the described procedures in animals produces a conditioned reflex avoidance dark space. When checking the reproducibility of reflex animals are placed in the light compartment in the corner opposite from the entrance to the dark compartment and see for 180 sec. Recorded in all cases when playing passive avoidance reaction latency time of the first entry in the dangerous dark compartment and the total time spent in the light and those who ω holds for a certain time interval. Developed the reflex was considered, if for all 180 sec observations animal never visited the dark compartment.

To study the effect of substances on the phase memory connection was introduced in various stages of formation memorable track. With the aim of obtaining data on the impact of substances on the process input and initial data processing the compound was administered 1 hour before procedure training [Spa, Laismina, SEO, Chassereau, Iniesta. The pharmacokinetics of some benzimidazole derivatives. Questions honey. chemistry, 2002, No. 3, s-258]. To study the ability to consolidate information, the target substance, the animals received directly after training. To obtain data on the impact of substances on the processes of reproduction of information, the connection was administered 24 hours after training. To assess the impact of the alleged nootropic drug on the processes of forgetting testing was carried out after 24 hours, 1, 2, 3 and 4 weeks. Before the experiment the animals were divided into 7 groups: group 1 - intact animals, which was administered intragastrically with 0.9% saline, group 2 - animals, which were injected Sol I 1 hour before training, group 3 - animals that received the connection I immediately after the procedure, training, and 4 animals, who were appointed preparat 24 hours after training. All animals received this compound at a dose of 10 mg/kg intragastrically [Spa, Overstroke, VAIDISOVA, Vahasalo, Iviagra. The influence of compounds with antioxidant properties on the functional activity of platelets. Experimental and clinical pharmacology, 1999, No. 1, ñ.38-40; Vahasalo, Iviagra, Spa. The use of antioxidant agents for the correction of DIC. Bulletin of the Volgograd scientific center of the Russian Academy of medical Sciences and Administration of the Volgograd region, 2005, No. 2, pp.24-27]. Similar three (5, 6, 7) groups were formed and drug compare Mexidol, which was administered at a dose of 100 mg/kg intragastrically [Kemzyme, Tauramena, Ldern. Antioxidants in the prevention and treatment of pathologies of the Central nervous system. M.: Izd. Institute of biomedical chemistry RAMS, 1991, 272 S.]

The statistical significance of the obtained results were evaluated using T-student criterion, criterion of Dunnet (q') when comparing multiple groups with the control, the survival of animals was assessed using non-parametric two-sided Fisher's exact method in the program Statistica 6.0 (StatSoft, USA).

It was found that the latency time in the control group of intact animals 24 hours after training increased 5.3 times (table 6), after 7 days after training 6.8 times, 14, 21 and 28 days 9.4, 11,07 and 12,12-fold, respectively, what about the comparison with initial values

Table 7, table 8. In groups where conducted to study the effect of substances on the measurement of the input and processing of the initial information is not observed as a significant increase in the latency time. So, in the group injected with a substance I latency time increased 4.1 times in 24 hours after training, and at 7, 14, 21 and 28 days 4.1; 3,76; 6,0; of 5.05 and 5,16-fold, respectively, compared with the original values. In animals that were injected Mexidol, observed an even lower increase in latency time, which amounted to 2.15 times a day after learning of 2.06 times in 7 days, 2 times for 14 days and 2.08 and 2.1 times for 21 and 28 days, respectively.

In groups, where they spent assessing the impact of substances on the ability to consolidate information, the most pronounced effect was observed in drug I. Thus, the latency time increased 5.3 times compared to the original rate after 24 hours after training, which was statistically significant. On day 7, the play traces in the memory latency time increased 7,06 times, and from the second week until the end of studies 100% of the animals did not go into the dark chamber. In the group of animals which were injected Mexidol, were not recorded such a significant effect. So, a day after learning of latent time was increased to 3.78 times, which was statistically significant; after 1 and 2 weeks 3.53 times and in 3,55 and 3.5 times for 21 and 28 days, respectively. In groups, where they spent assessing the impact of substances on the reproduction information and the maximum effect was seen in months, and as compared with the group of RU-a, and compared with the control group.

Thus, the latency time in the group, where he injected the drug I, after 24 hours has increased cent to 8.85 time, a week, 5,16 time in two weeks 7,13 time, after 21 days in 7.33 times and after 28 days in 7,44 times. In the group, where he introduced Mexidol, latency time after 24 hours were statistically significantly increased 12.5 times, then 100% of the animals throughout the research did not go into the dark compartment.

The analysis of this indicator, as the time spent in a dark cell, shows how quickly the animal remembers being in this compartment is dangerous. Thus, in the control group, this figure after 24 hours has decreased by 3.6 times, on day 7 of the study 1.4 times, to 14 days in 1,91 times and at 21 and 28 days 2.02 and 13,23 times, respectively. In groups where the substance was administered to assess the input and processing of information, watched multidirectional effects. So, in the group, where he entered the compound I, the time spent in the dark chamber continuously decreased. The maximum reduction was observed after 24 hours at 5.17 times, a week later, the figure had decreased to 2.79 times, and at 14 days, the rats did not go into the dark compartment. 21 the ducks the time spent in the dark compartment was decreased in 2,43 times, and at 28 days of only 1.39 times compared with the original values. In the group, where he introduced Mexidol, the decrease of this indicator was observed only when playing a reflex after 24 hours in a 8.34 times. In other cases, this figure was increased 8,54; 8,49; 8,15 and 7.34 times of 7, 14, 21 and 28 days, respectively, indicating that the deficit recovery memorable track, and this trend is observed in the group which assessed the ability to consolidate information. So, the time spent in the dark compartment was decreased only when playing a reflex in 24 hours in MT 18 : 34 times. In the study on days 7, 14, 21 and 28 days figure was increased 3,18; 2,27; 3,09 and 3.05 times, respectively. In a similar group, where he introduced salt I, the time spent in the dark compartment was decreased after 24 h in 4.4 times and on day 7 1.72 times. On 14, 21 and 28 days, the animals did not go into the dark compartment. In groups, where they assessed the ability of substances to affect the reproduction of the information observed the opposite effect. In animals that were administered compound I decreased the time spent in the dark compartment only after 24 hours when playing passive avoidance reaction. In other cases, this figure was increased to 4, 15; 2,9; 1,35; and 2.8 times of 7, 14, 21, and 28 days, respectively, compared with the original values. In the group, where he introduced Mexidol, the time spent in the dark compartment with whom was igalas in 14,34 times in 24 hours after training. 7, 14, 21 and 28 days 100% of animals not entered the dark compartment. When assessing the time spent in the light chamber found that this figure was decreased in all the groups studied, indicating the preservation of the memories of the application of the aversive stimulus in a dark cell. So, in the group of intact animals by the end of the experiment (28 day), this figure has decreased 12,63 times, while all groups were injected substances, only 28 days this indicator was equal to zero.

Table 6
The effect of compound I and Mexidol on the formation of traces in the memory in rats 24 h after training
GroupPassive avoidance reaction, learningPassive avoidance reaction, check in 24 hours
The latent timeDark chamber, withLight. cameraThe latent timeDark chamber, withLight camera
K113,7±3,5057,3±30/78109,5±32,30 72,70±37,7016,00±10,2092,30±33,80
E130,0±11,1335,0±16,73115,0±24,50123.17±39,406,83±4,7450,00±34,67
E221,83±9,4044,33±29,70113,83±26,0115.5±33,9810,33±of 6.4954,17±28,09
E3 effects17,17±9,7819,83±9,12143,0±is 18.4097,17±40,88.67±4,2077,5±36,52
M170,83±38,094,17±1,6898,33±34,54to 152.0±at 30.670,5±0,5527,5±30,12
M242,67±30,59,17±2,20128,17±28,67161,17±20,630,5±0,5518,33±20,08
M312,0±5,447,17±1,56160,83±5,70150,17±32,70,5±0,5529,33±32,13

K1 - control group of intact animals;

E1 - the group of animals treated with compound I for 1 hour prior learning passive avoidance reaction;

E2 is a group of animals who were injected compound I directly after learning of passive avoidance reaction;

E3 effects - a group of animals who were appointed by the connection I 24 hours after learning of passive avoidance reaction;

M1 - the group of animals treated with Mexidol 1 hour prior learning passive avoidance reaction;

M2 is a group of animals that wodele Mexidol immediately after learning of passive avoidance reaction;

M3 is a group of animals who were appointed Mexidol 24 hours after learning of passive avoidance reaction;

data are statistically significant compared with control K1 (p<0,05).

Table 7
The effect of compound I and Mexidol on the formation of traces in the memory in rats after 7 and 14 days after training
GroupPassive avoidance reaction, 7 dayPassive avoidance reaction, check in 14 days
The latent time Dark chamber, withLight. cameraThe latent timeDark chamber, withLight camera
K193,67±42,339,17±30,9847,17±33,53129,0±35,4230,0±27,1917,67±17,25
E1112,83±38,8612,67±11,3654,5±31,52180,0±0,00--
E2154,17±28,325,83±28,3-180,0±0,00--
E3 effects88,67±40,1882,33±35,969,0±to 6.43122,5±39,8457,5±39,84-
M1144,4±39,8035,6±39,80-144,6±39,58 35,4±39,58-
M2150,83±31,9529,17±31,95-159,17±22,820,83±22,82-
M3180,0±0,0--180,0±0,00--

K1 - control group of intact animals;

E1 - the group of animals treated with compound I for 1 hour prior learning passive avoidance reaction;

E2 is a group of animals who were injected compound I directly after learning of passive avoidance reaction;

E3 effects - a group of animals who were appointed by the connection I 24 hours after learning of passive avoidance reaction;

M1 - the group of animals treated with Mexidol 1 hour prior learning passive avoidance reaction;

M2 is a group of animals who were injected Mexidol immediately after learning of passive avoidance reaction;

M3 is a group of animals who were appointed Mexidol 24 hours after learning of passive avoidance reaction.

Table 8
The effect of compound I and Mexidol on the formation of traces in the memory in rats after 21 and 28 days after training
GroupPassive avoidance reaction, after 21 daysPassive avoidance reaction, test after 28 days
The latent timeDark chamber, withLight. cameraThe latent timeDark chamber, withLight camera
K1151,67±31,0428,33±31,04-167,0±10,894,33±3,308,67±9,49
E1151.67±37,0414,50±15,8913,83±br15.15154,67±27,7525,33±27,75-
E2180.0±0,00--180,0±0,00--
E3 effects125,83±37,6926.67±27,0827,5±25,05127,83±36,1455,5±38,45 -
M1146,00±38.0134,00±38,01-149,4±34,2130,6±34,21-
M2151,67±31,0428,33±31,04-to 152.0±30,6728,0±30,67-
M3180,0±0,00--180,0±0,00--

K1 - control group of intact animals;

E1 - the group of animals treated with compound I for 1 hour prior learning passive avoidance reaction;

E2 is a group of animals who were injected compound I directly after learning of passive avoidance reaction;

E3 effects - a group of animals who were appointed by the connection I 24 hours after learning of passive avoidance reaction;

M1 - the group of animals treated with Mexidol 1 hour prior learning passive avoidance reaction;

M2 is a group of animals who were injected Mexidol immediately after learning of passive avoidance reaction;

M3 is a group of animals who were appointed Mexidol 24 hours after learning of passive avoidance reaction.

Conclusion

1. Antioxidant compound I showed a high proteoliposomes the th activity in models of acute hypoxia, comparable to the activity of the reference drug gutimin, acting in much smaller doses. It should be noted a wide range of antihypoxic activity of the new compounds in models of hypoxia of different Genesis, which allows us to talk about the universality of their antihypoxic action.

2. The connection I quite markedly improve efficiency in animal models associated with ultimate loads (swimming to failure), and with the speed of development of fatigue. In comparison with the reference act-protective tool bemythyl compound I showed a greater intensity of the effect, which was realized in less than bemythyl, doses. When swimming animals in a complicated antiorthostatic conditions connection I clearly exceeded the preparation of comparison bemythyl on act-protective properties.

3. It was shown that the ability of antioxidant compounds I to affect the cognitive and higher integrative animal performance. It was found that it was mainly improved the ability to consolidate information, and drug comparisons Mexidol mainly affect the ability of animals to reproduce information. The data obtained indicate the presence of compound I nootropic activity.

1. The use of dihydrobromide 9-(2-diethylaminoethyl)-2-(3,4-dioxy-phenyl)imide is zo[1,2-a]benzimidazole of the formula I

as biologically active compounds with antihypoxic, act-protective and nootropic activities and positive impact on physical performance.

2. The pharmaceutical composition antihypoxic, act-protective, nootropic action and a positive influence on physical activity, containing as an active start dihydrobromide 9-(2-diethylaminoethyl)-2-(3,4-dioksifenil)-imidazo[1,2-a]benzimidazole of the formula I

taken in an effective amount.



 

Same patents:

FIELD: medicine.

SUBSTANCE: invention relates to field of veterinary. Method includes introduction of ferroglucinum-75 solution in dose 15 mg of iron per 1 kg of live weight of calf body, one time, intramuscularly and drinking of glicopin in dose 6.0 mg/day is the morning during 6 days, starting simultaneously with injection of ferroglucinum.

EFFECT: method makes it possible to stably normalise thrombotic hemostasis in newborn calves with iron-deficient anemia, ensures long-time support of thrombotic hemostasis in optimal mode of functioning, excludes risk of thrombotic complications and assists normal growth and development of calves.

2 ex

FIELD: medicine.

SUBSTANCE: invention relates to field of veterinary. Method includes introduction of ferroglucinum-75 in dose 15 mg of iron per 1 kg of live weight of calf intramuscularly, one time and drinking of glicopin in dose 6.0 mg/day is the morning during 6 days, starting simultaneously with injection of ferroglucinum.

EFFECT: claimed method makes it possible to avoid vascular complications in newborn calves with iron-deficient anemia, make the herd healthier, reduce murrain, increase volume and quality of obtained meat and milk production, obtain healthy offspring from the animals.

2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention describes the pyrrolo- and thiazolopyridinium compounds and their pharmaceutically acceptable salts covered by general structural formula I: wherein the values A, B, R1, R2, R3, R4, R5, R6, R7 and R8 are those as presented in cl.1, and a pharmaceutical composition based on the given compound for inhibition of hypoxia-inducible factor (HIF) hydroxylase activity.

EFFECT: there are produced and described new compounds able to modulate hypoxia-inducible factor (HIF) stability and/or activity.

29 cl, 178 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel cyanoisoquinoline derivatives of formula I , where R is selected from a group comprising hydrogen and C1-C10 alkyl, R1, R2, R3 and R4 are independently selected from a group comprising hydrogen, halogen, hydroxy, C1-C10 alkyl, substituted with 1-3 halogen atoms or C6-C14 acryl, C6-C14 aryl, -OR7, -SR7 and -SO2R7, where R7 is selected from a group comprising C1-C10 alkyl, C1-C10 alkyl substituted with C6-C14 aryl, C3-C10 cycloalkyl, C6-C14 aryl and C7-C8 heteroaryl containing 1-2 heteroatoms selected from a group comprising N, O and S, where C6-C14 aryl and C7-C8 heteroaryl are optionally substituted with 1-3 substitutes selected from a group comprising halogen, C1-C6 alkoxy, C1-C10 alkyl, C1-C6 dialkylamino and C4 heterocyclyl containing 2 heteroatoms selected from a group comprising nitrogen and oxygen, and R5 and R6 are independently selected from a group comprising hydrogen and C1-C3 alkyl, or pharmaceutically acceptable salts thereof. The invention also relates to novel cyanoquinoline derivatives of formula II , where R31, R32, R33 and R34 are independently selected from a group comprising hydrogen, hydroxy, halogen, C1-C10 alkyl substituted with 1-3 halogen atoms or with C6-C14 aryl, C6-C14 aryl, -OR37, -SR37 and -SO2R37, where R37 is selected from a group comprising C1-C10 alkyl, C1-C10 alkyl substituted with C6-C14aryl, C3-C10 aryl, C7-C8 heteroaryl containing 1-2 heteroatoms selected from a group comprising N, O and S, where C6-C14 aryl and C7-C8 heteroaryl are substituted with 1-3 substitutes selected from a group comprising halogen, C1-C6 alkoxy, C1-C10 alkyl, C1-C6 dialkylamino C4 heterocyclyl containing 2 heteroatoms selected from a group comprising nitrogen and oxygen, R35 denotes hydrogen or methyl, or pharmaceutically acceptable salts thereof. The invention also relates to specific cyanoisoquinoline compounds, a pharmaceutical composition based on the compound of formula I, a hypoxia-inducible factor (HIF) hydroxylase inhibiting method, a method of treating, preventing or slowing down development of a condition associated with hypoxia-inducible factor (HIF), a condition associated with erythropoietin (EPO), anaemia, based on use of the compound of formula I.

EFFECT: obtaining novel cyanoisoquinoline compounds having useful biological properties.

42 cl, 1 tbl, 54 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to an oral food additive which contains anhydrous ferric pyrophosphate, ferric pyrophosphate monohydrate or nonahydrate and copper citrate. The invention also concerns a method for preparing said additive and using it for balanced iron intake in the patient.

EFFECT: additive under the invention has no unpleasant metal taste even in the absence of flavouring and taste masking ingredients.

19 cl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to veterinary science. The preparation contains a mixture of colloidal iron, a ligand, zinc, cobalt, selenium and water. The ligand is presented by Triton X-100 (polyethylene glycol mono (tetramethylbutanol) phenyl ester) in the following proportions, mg: colloidal iron (III) 35.0-45.0; Triton X-100 0.2÷0.6; zinc (II) 0.1÷0.3; cobalt (II) 0.05÷0.15; selenium (IV) 0.02÷0.04 and water up to 1000.0.

EFFECT: preparation exhibits high therapeutic and preventive efficacy, low toxicity, keeps dispersion and shows high storage stability.

5 cl, 12 tbl, 13 ex

FIELD: chemistry.

SUBSTANCE: invention relates to pharmaceuticals and medicine and pharmaceutically acceptable derivatives of 2-aminobenzothiazole of general formula 1.

EFFECT: high anti-hypoxic activity and high effectiveness of treatment.

7 cl, 3 tbl, 6 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely obstetrics, and can be used for treating anaemia in pregnant women. For this purpose, iron preparations are added with Poetam 900 mg/day. The length of the therapeutic course is 3 weeks in moderate severity of anaemia, 6 weeks - in severe anaemia, and 8 weeks - in very severe anaemia.

EFFECT: method provides intensified therapeutic effect ensured by stimulating production of endogenous renal erythropoietin and higher concentration of sulphhydryl groups and lipoproteins in red blood cell membranes with no side effects.

6 tbl, 1 ex

FIELD: medicaments.

SUBSTANCE: present invention provides water-soluble iron-carbohydrate derivative complexes which are suitable for the therapy of iron deficiency states, and the preparation thereof, medicaments comprising them, and the use thereof in the prophylaxis or therapy of iron deficiency states. The medicaments are suitable in particular for parenteral administration. A water-soluble iron-carbohydrate derivative complex obtained from the reaction of an aqueous iron (III) salt solution and (b) an aqueous solution of the product of the oxidation and subsequent derivatization of one or more maltodextrins, wherein the oxidation is carried out with an aqueous hypochlorite solution at a pH value in the alkaline range, wherein when one maltodextrin is used its dextrose equivalent is from 5 to 20 and when a mixture of a plurality of maltodextrins is used the dextrose equivalent of the mixture is from 5 to 20 and the dextrose equivalent of the individual maltodextrins in the mixture is from 2 to 40, and the subsequent derivatization is carried out with a suitable reagent. The process for the preparation of the iron-carbohydrate complex, wherein one or more maltodextrins is oxidized in aqueous solution, at an alkaline pH value, with an aqueous hypochlorite solution, the subsequent derivatization is carried out with a suitable reagent, and the resulting solution is reacted with the aqueous solution of an iron (III) salt, wherein when one maltodextrin is used its dextrose equivalent is from 5 to 20 and when a mixture of a plurality of maltodextrins is used the dextrose equivalent of the mixture is from 5 to 20 and the dextrose equivalent of the individual maltodextrins in the mixture is from 2 to 40.

EFFECT: most derivatised maltodextrin ligands exhibit increased stability towards enzymatic degradation by amylase as compared with underivatised maltodextrin, which can promote retarded and uniform degradation of the iron-maltodextrin derivative complexes according to the invention in the body.

15 cl, 11 tbl, 45 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed is haemostimulating medicine, representing immobilised on polymer recombinant erythropoietin, characterised by the fact that recombinant erythropoietin is immobilised by electron-emitting impact by its introduction into solution of low-molecular water-soluble polymer (PEG, polyvinyl pyrrolidone, hydroxyethyl starch with molecular weight 400-4000 Da), preliminarily subjected to impact of ionising irradiation in dose 1-5 Mrad, to final concentration 500-5000 IU in 1 ml of solution. Shown is more expressed specific activity of medication in case of parenteral and per oral intake in comparison to medication "Mircera".

EFFECT: claimed medication does not possess immunogenic properties and does not demonstrate signs of allergenic action.

4 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to veterinary science. A detoxicant of polysilicic acid derivatives is specified in a group of reversed-phase sorbents.

EFFECT: using the detoxicant enables practically eliminating toxic effects accompanying animal's poisoning.

2 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention concerns veterinary science. A polyfunctional enterosorbent contains schungite-containing minerals comprising silicon dioxide 15.0-70.0 wt %, with an average median particle size 15.0*10-6 m.

EFFECT: invention provides higher efficacy on a wide spectrum of toxic substances, including mycotoxines, nitrates, nitrites, heavy metal salts, and also as an antibacterial and antioxidant agent.

14 tbl, 14 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to zinc-containing antidote of lethal and severe poisonings with carbon monoxide. Claimed antidote represents intramolecular tricyclic complex of triethanolamine with zinc salts of inorganic or organic acids (2, 8, 9-trihydrozincatrane) with ratio of triethanolamine to zinc salts being 1:1. Invention also relates to method of protection against poisoning by carbon monoxide by peroral introduction into organism of zinc-containing antidote in 5 vol. % ethanol in dose range 20-60 mg/kg of body weight.

EFFECT: prevention of lethal poisoning with carbon monoxide, higher efficiency and reducing acute toxicity of zinc-containing antidote.

9 cl, 5 ex.

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to toxicology, and can be used for treating rats with acute verapamil intoxications. That is ensured by administering sodium thiosulphate 15-20 mg per 100 g of rat's weights as a cardioprotector.

EFFECT: method provides improved central venous pressure value.

3 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to zinc-containing antidote of lethal and severe poisonings with ethanol. Claimed antidote represents intramolecular tricyclic complex of triethanolamine with zinc salts of inorganic or organic acids (2, 8, 9-trihydrozincatran), the ratio of triethanolamine to zinc salts being 1:1. Invention also relates to method of treating ethanol poisoning by introduction into organism of zinc-containing antidote in 5 vol.% ethanol in dose range 30-60 mg/kg of body weight.

EFFECT: prevention of lethal outcome in case of ethanol poisoning and reduction of acute toxicity of zinc-containing antidote.

9 cl, 5 ex

FIELD: chemistry.

SUBSTANCE: Chinese magnolia is extracted with liquefied carbon dioxide. The obtained CO2 extract undergoes chromatographic separation on aluminium oxide and eluated with hexane. After eluation the obtained hexane fractions are frozen and recrystallised from the chloroform-hexane mixture in ratio of 1:10-3:10.

EFFECT: high output of product.

1 ex

FIELD: medicine; veterinary science.

SUBSTANCE: method consists in introduction to an experimental animal of Acyzol 30 mg/kg once a day combined with daily subcutaneous introduction of cadmium sulphate solution in a dose 0.1 mg/kg.

EFFECT: prevention of cadmium toxic effect in chronic poisoning in experimental animals.

2 cl, 1 tbl, 1 ex

Medicinal agent // 2363463

FIELD: medicine.

SUBSTANCE: invention relates to medicine and pharmaceutical industry, and more specifically to making tableted dosage form with prophylactic effect for arresting primed reaction to radiation and early transient incapacity. The agent contains ondansetron, methacin and caffeine in weight ratio ondansetron:methacin:caffeine 4:1:20-300.

EFFECT: reduced adverse reaction, more specifically vomiting, diarrhea and reduction of physical activity.

5 cl, 11 tbl

FIELD: medicine.

SUBSTANCE: claimed is remedy possessing antitoxic properties in case of aliphatic alcohol poisoning. As such polyosm - 30% solution of polyethylene oxide 400 is suggested. It is shown that polyosm protects animals against death (100% in control) in case of isopropyl alcohol poisoning.

EFFECT: water content in lungs is analogous to index of intact animals at moderate reduction of respiration rate.

6 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: invention refers to veterinary science, in particular to products intended to increase capacity for survival and yield of poultry. For this purpose common composition 1,3-di(3-piperidine-2-hydroxypropyl)-6-methyluracil of formula: is used. Composition is characterised by natural resistance, antioxidant activity, activates nonspecific factors of immune system, as well as possesses medicinal properties to provide detoxification of nitrates and nitrites. Composition has the appearance of white powder, is highly soluble in water and can be added in specified doses to chickenfeed.

EFFECT: production of composition providing increase of capacity for survival and yield of poultry.

6 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: invention refers to pharmaceutics and medicine and concerns a pharmaceutical composition for treating and preventing preexcitation syndrome (WPW-syndrome) containing 9-diethylaminoethyl-2-tert-butyl-imidazo[1,2-a] benzimidazole dihydrochloride of formula I as an agent.

EFFECT: composition shows high efficacy.

6 cl, 6 tbl, 2 ex

Up!