Pharmaceutical agent

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to biologically active substances displaying perspective using medicine, veterinary science, cosmetics and dairy industry. Agent comprises polyoxyarylene ester and hydroquinone in their ratio from 83:17 to 5:95, respectively. Agent comprises 2-(1-oxy-4-hydroxyphenylene)benzoquinone or 4-hydroxyphenylene-2,4-dioxybenzene as a polyoxyarylene ester. Method for preparing agent involves mixing polyoxyarylene ester with hydroquinone and wearing the prepared mixture up to formation of the uniform mass. Invention provides creature of a novel agent of the broad spectrum of effect, namely: antioxidant, antihypoxic, antitumor, radioprotective, immunostimulating and biocide effects.

EFFECT: valuable properties of agent.

7 cl, 20 tbl, 16 ex

 

The invention relates to medicine, namely to biologically active substances (BAS), are promising for use in the food and dairy industry, medicine, veterinary medicine, cosmetics and related industries.

Known for the numerous group of substances with antioxidant (AO) and/or antihypoxant (AG) action. These include, in particular, cytochrome C, ubiquinone, metalfinishing, BHT and other (Mashkovsky PPM Medicines - M.: Medicine, volume 2, p.73-76; encyclopedia of drugs, ISD, - M.: radar. 2001. 1503 S.; Reference VIDAL, - M: Attraversare, 2001, 725 S.; V.M. Vinogradov Pharmacology and toxicology, Sat. - Kiev: Health, 1972, No. 7, pp.163). Thus, in particular, ubiquinone (coenzyme Q) in the dose of 200 mg/kg of body weight has a positive effect on the cells in some conditions of hypoxia, as a natural carrier of electrons and occupying a Central place in the chain of enzymes of electron transport, reacting with three enzyme systems; ABOVE, N-oxidase, succinate KoQ-reductase and cytochromes (U.S. Pat. Of the Russian Federation No. 1746886, 1991, CL SR 32/06; PCT application 96/08527, 1996, CL 08G 61/10).

The disadvantages of most of these substances is a narrow spectrum of action, due to a significant number of contraindications, lack of effectiveness, sophisticated production technology.

Wide is rasprostranenie received derivative of poly-hydroxy-fenelonov (PEF) - the drugs manufactured under the trademarks - Olifen, Trifan, Lipoxen, Spirit (PCT application No. 96/08527. 1996 class. 08G 61/08527). A characteristic feature of poly-hydroxy-fenelonov is a high degree of conjugation of molecules that, when introduced into the body can actively affect the bioenergetic processes in cells, to capture and "suppress" free radicals, influence on blood rheology.

These properties led to a wide range of application of the substances of this group, which is the analogue of the claimed inventions properties. In particular, PEF found use as as drugs that provide the overall normalizing effect on the functioning of cells and cellular systems of the body (EN 2121852, 1999, CL. AC 31/375).

The compounds of this type was obtained by polymerization of parabenzoquinone in the presence of alkaline agents in aqueous-acetone medium containing substances, providing an introduction to polymer replacement groups, for example, sodium thiosulfate or guanidine, followed by separation of the target product by extraction or other methods.

The disadvantage of compounds of this type is to obtain in the reaction mixture of oligomers, which leads to poor standardisointi drug, poor solubility of compounds in water, an unpleasant taste, presence of complications (especially when in trevenna the introduction), not enough high efficiency, stimulating effect on the growth of microorganisms (SU 820195), which is a negative factor for long term storage of drugs and compositions based on them.

Known developed by the author BAS representing derivatives polyoxyethylenated esters (POEA), which are based on two benzene ring or benzene and quinoid rings connected by ether bond (EN 2224737, 2002; EN 2230467, 2003 - class. AC 31/05).

The compounds obtained along with pronounced antihypoxant and antioxidant properties have a broad spectrum of biological effects, in particular, show a pronounced biocidal action. However, these properties, as studies have shown, can be substantially enhanced, and the range of their actions has been significantly expanded.

The closest in structure and properties is a 4-hydroxyphenyl-2,4-dioxobenzo (EN 2224737, 2002, - CL AC 31/05), manifesting when introduced into the body combined antioxidant (AO) and hypoxic (AG) action.

However, these properties of matter can be enhanced when used in the composition. This composition, in particular, can combine these properties with the ability to protect the body from exposure to ionizing radiation and to be promising in the treatment of cancer Zab is problems.

Know the use for the treatment of cancer and similar diseases a large number of pharmaceutical preparations, such as embihin, cyclophosphamide, degranol, dipin, imits, fotrin; cytostatics, antibiotics, antimetabolites, Vinca alkaloids, hormones, etc. (Mashkovsky PPM Medicines. - M.: Medicine, 1985, vol. 1-2. - 585 S.).

The disadvantages of most drugs are high toxicity, numerous negative side effects, relatively low efficiency.

Widely used as anti-cancer drug currently got cytokines, in particular interferon, used both independently and as part of a comprehensive treatment (Malinovskaya CENTURIES, murzabaeva GT, Manakova PS and other Functioning of the system of interferon in different ways and doses of alpha-2-interferon // Virology. - 1989. - T - N2. - S-183). However, these drugs are very expensive, have limitations for use.

Preparations of interferons are the closest analogues for use of the claimed anti-cancer drug.

In the treatment of cancer as part of a comprehensive treatment greater role of radiotherapy in which the area of the tumor is exposed to fluxes of ionizing radiation. Due to the negative impact of radiation is the AI on the body in General are of greatest interest medication, combining anti-cancer properties with radioprotective.

Currently, as radioprotectors use drugs such as tsistamin hydrochloride, Maximin, batil, tezan and others (Mashkovsky PPM Medicines. - M.: Medicine, 1985, Vol.2. - p.189-191).

However, these drugs are not cancer, have a large number of contraindications and lead to failure of the life support systems of the body.

Closest to the claimed drug combining anticancer and radioprotective properties is BAD "Clairin", which is an extract of callus tissue of plants Ungernia Victora, containing 0.02% of active principle (polysaccharides) (EN 2141838, 1999; EN 2147439, 2000 - CL. AC 35/78).

The disadvantage of the BAD is the practical impossibility of selection of the active principle in higher concentrations, the instability of polysaccharides during storage, limited natural resources, because the plant is endemic.

The technical problem solved by the author, was the creation of the composition, the reinforcing properties of POAA and expanding the scope of their potential applications, in particular exhibiting antitumor and radioprotective action.

The technical result is achieved due to the use of a composition containing a mixture of POAA with hydroquinone in a mass ratio of from 99:1 e is 1:99. At the same time as POAE can be used as a 4-hydroxyphenyl-2,4-dioxobenzo (HKEx)received on EN 2224737 and 2-(1-hydroxy-4-hydroxyphenyl) benzoquinone (OHH)received on EN 2230467, as well as the products of their interaction with hydroquinone.

The emergence of new properties of the composition, apparently caused by the interaction between the polarized molecules of POAE, which are characterized by paired structure of molecular orbitals and polarized molecules hydroquinone (GC)that interact and allow you to get sverhnapryazheniya complexes both in solution and as a result of contact between the powders of the ingredients.

The probability of occurrence of such complexes increases if the conduct intensive grinding mixtures of POAA and GC in a mortar, a ball mill or by using a disintegrator. The rise time of abrasion (example 3) leads to a change in properties of the composition, in particular to increase up to a certain limit antioxidant characteristics. Because during the mixing of the solid-phase reaction between the components is not complete, then the resulting composition typically contains a mixture of GC, traditional POAE and complex POAE·TX.

The method of obtaining the composition thus consists in mixing the ingredients in a dry form, and grinding the mixture to obtain a uniform m is ssy. The time of abrasion depends on the composition used for this purpose, a mixture of used equipment and features requirements to receive the drug.

As shown by experiments, the new composition has a stronger AO and AG properties compared with the relevant ingredients biocidal effect against microorganisms, as well as an effective impact on the individual organs and systems of the human body or animal, and on the organism as a whole. These properties, in particular, manifested in anticancer, radioprotective and immunostimuliruyushhim action.

The method of obtaining the composition thus consists in mixing the ingredients in a dry form, and grinding the mixture.

Composition, depending on the composition has LD50from 800 to 6500 mg/kg; LD16from 300 to 1500 mg/kg of body weight, LD84from 3000 to 6500 mg/kg of body weight for the occasional admission of not more than 5 mg/kg of body weight. Compared with Olivenol song about 3-5 times less toxic. The rate of acute lethal toxicity data and morphological studies it can be attributed to class IV hazardous substance (GOST 12.1.007-76. SSBT. "Harmful substances. Classification and General safety requirements. These toxicomanie, observations of experimental animals for 14 days after the strictly introduction, and necropsy data allow you to take it to class IV low toxic drug vases (H.Hodge et all. Clinical Toxilogy of Commercial Products / Acute Poisoining. Ed. IV, Baltimore, 1975, 427 p.) Currently, obtained permission for its use as a food additive. Conducting further tests to study the properties of the composition and the mechanism of its action.

The drug is introduced orally or topically in the form of ointments, emulsions, powders, solutions in water, juice, Vodopyanova mixtures and other compositions. When the oral composition is used alone or in a mixture with other ingredients as food or feed additives. Depending on the form of application and characteristics of the tasks we choose the optimal composition, because depending on the content of certain ingredients of its properties vary within very wide limits and is very unequal.

The nature and advantages of the invention are illustrated by the following examples.

Example 1. Sample hydroquinone and 4-hydroxyphenyl-2,4-dioxybenzone (HKEx), the resulting technology EN 2224737, were weighed and mixed in a predetermined ratio. The composition of the obtained compositions are given in table 1.

Table 1

The compositions based on the HKEx
no songs Composition, % wt.
hydroquinoneHKEx
Composition 1991
Composition 2955
Composition 39010
Composition 46634
Composition 53466
Composition 61090
Composition 7199

Example 2. Sample hydroquinone and 2-(1-hydroxy-4-hydroxyphenyl) benzoquinone (OHH)obtained by EN 2230467, were weighed and mixed in a predetermined ratio. The composition of the obtained compositions are given in table 2.

Table 2

The compositions based on OGH
no songsComposition, % wt.
hydroquinoneOHH
Composition 8991
Composition 9955
Composition 109010
Composition 117030
Composition 123466
Composition 13 1090
Composition 14199

Example 3. The compositions obtained in examples 1 and 2, (#2 and # 11) were subjected to further processing by rubbing in a mortar (IP) or a ball mill (BL) or by passing through a disintegrator (DI). The resulting mixture was determined by the GC content of free and PFA, on what basis was calculated the number of GC associated to the complex and assessed the antioxidant aktivnosti.

For analysis of total antioxidant activity of substances used spectrophotometric method with guanidinum reagent and Riboflavin in optical density at a wavelength of 460 nm on a spectrophotometer SF-56. The results are shown in table 3.

Table 3

The compositions after additional processing mixtures
no songsA method of processingThe compositionIndicator of antioxidant activity (Ed. opt. PL/mg protein
GCPOAEPOAE·HS
HKEx
Composition 2Without processing 955-20±4
Composition 25 min abrasion94.7±0.24.8±0.20.5±0.325±4
Composition 210 min abrasion94.7±0.64.3±0.61.0±0.632±5
Composition 215 min abrasion94.0±0.54.0±0.52.0±0.534±4
Composition 220 min abrasion93.8±0.63.4±0.22.8±0.738±4
Composition 225 min abrasion93.3±0.43.6±0.43.1±0.540±5
Composition 230 min abrasion93.1±0.53.6±0.43.3±0.540±4
OHH
Composition 11 Without processing7030-32±5
Composition 1120 min abrasion66.8±0.627.4±0.56.8±0.738±4
Composition 11BL 5 min65.2±0.627.0±0.67.8±1.040±4
Composition 11BL 10 min65.8±0.626.4±0.68.0±0.642±5
Composition 11Cage mill65.0±0.627.4±0.67.6±0.438±5

Example 4. The influence of the composition of the drug on the radioprotective properties.

Radioprotective effect of the preparations was studied in mice TWO/2. The drugs were injected with drinking ode for 3 days before exposure to x-ray machine and 10 days after irradiation. Animals of the control group received water without additives. Irradiation was carried out at the end of 3 days the use of drugs intermediate between sublethal and lethal doses of the - 630 am Glad.

For the evaluation of radioprotective action examined the influence of drugs on the formation of endogenous colonies in the spleens of irradiated mice with bone marrow cells. Mice were scored after 10 days after exposure, removed the spleen and fixed them in the lock Buena. The number of colonies was counted with the naked eye. When determining the average number of colonies and their standard deviations were obtained the results given in table 4.

70 5.0±0.5
Table 4

The influence of composition and doses of drug used at the radioprotective properties of composition
The compositionProcessingDose, mg/mouseThe number of colonies on the spleen
hydroquinonePOAE
control--4.0±0.2
OHH
7030BL, 10 min0.0013.6±0.3
7030BL, 10 min0.014.1±0.2
7030BL, 10 min0.16.8±0.3*
30BL, 10 min1.011.6±0.4*
7030BL, 10 min5.09.2±0.7*
7030BL, 10 min1.011.6±0.4*
7030no1.09.4±0.4*
991no1.04.8±0.5*.
955no1.05.3±0.4*
9010no1.05.8±0.5*
6634no1.08.4±0.5*
3466no1.09.0±0.4*
1090no1.08.1±0.6*
199no1.07.3±0.7*
HKEx
991no1.04.1±0.5
955no1.04.4±0.4
9010no1.0
7030no1.07.4±0.4*
3466no1.08.2±0.4*
1090no1.07.6±0.5*
199no1.05.8±0.5*
7030BL, 10 min1.08.8±0.4*
3466BL, 10 min1.09.9±0.7*
1090BL, 10 min1.08.2±0.5*
* R>005.

Songs without processing the received index And, after processing the index N.

Example 5. For further research used mainly compositions containing

- 17% wt. GC and 83% wt. HKEx (drug Epogen);

- 5% wt. OHH and 95% wt GH (drug Epogen);

- products of their processing in a ball mill for 10 min.

accordingly drugs Epogen-N and Epogen-N

Epiphany was a monocrystalline powder black. pH of 1% solution is 8.0-8.2, LD50(rat-SAMC is)=6420± 180 mg/kg

Ephiny was a single-crystal powders in dark gray. 1% solution of pH 7.6-7.8, LD50(rat-male)=3820±120 mg/kg

Example 6. The antitumor effect of the drug.

The effect was studied at 70 mice-females series GSWA (C57B1)6 weighing 18-20, Animals were cultivated diploid variant ascitic Ehrlich tumor intraperitoneally at 106 cells in 0.2 ml of ascites.

Study drug daily for 15 days after inoculation of the tumor daily basis from the date of inoculation of the tumor, is administered orally in the form of an aqueous solution containing 5 mg of the drug on the mouse. As control was used 15%solution of alcohol. As the lifespan of mice with ascitic form tumors on average 14-16 days, the fence animals was carried out on the 5th and the 10th day after inoculation.

Evaluation of the effectiveness of the drug was carried out on the basis of the number of tumor cells in 1 ml of ascites (OKA) and the number of tumor cells per 1 g of the weight of the animal (SLE). The number of tumor cells in 1 ml of ascites was determined using the camera Goryaeva according to the usual method.

Simultaneously assessed the condition of the immunocompetent organs - thymus and spleen to change its relative weight on the 5th and the 10th day after inoculation of the tumor. The results are shown in table 5.

The results svidetelstvujut efficacy in a wide range of concentrations. It is known that tumor process causes an increase on day 5 relative spleen weight at 85%, which corresponds to the data control. Compensation of this phenomenon with the drug indicates the protective effect of the drug.

Table 5.

The effectiveness of composition on the development of ascitic Ehrlich tumor in mice (in a fraction of the degree of braking)
Days after vaccinationIndexControlEpogen-Epogen-NComp-NComp-7-NEpogen-Epogen-NComp-N
5Rel. the weight of the thymus2.5±0.82.3±0.72.1±0.52.5±0.62.2±0.82.4±0.82.2±0.72.2±0.5
Rel. weight10.7±2.48.2±0.77.1±0.810.2±0.66.7±0.67.2±0.77.1±0.87.7±0.6
spleen23%34%5%37%34%35%28%
OKA, OKB
10Rel, the weight of the thymus0.9±0.40.8±0.40.7±0.40.8±0.40.7±0.40.8±0.40.7±0.40.8±0.4
Rel. the weight of the spleen4.9±1.64,9±1.55.9±1.64.0±1.56.7±1.67.7±1.56.6±1.65.8±1.5
OKA200±7060±3052±30130±5086±3040±1040±1072±30
70%74%35%57%80%80%64%
OKB50±820±613±540±1012±610±410±412±5
60%74%20%76%80%80%76%
Rel. in ascites0.24±0.030.23 0.030.21±0.030.24±0.030.21± 0.030.20±0.030.16±0.030.18±0.03

Example 7. The efficacy of compositions of Epogen-N in Oncology was conducted at the research Institute of experimental diagnostics and therapy of tumors of the Russian oncological scientific center named. Ban RAMS in treatment of women with breast cancer in the inpatient unit 32 patients at the age from 32 to 50 years old who had received chemo - and radiation therapy in combination with the intake of antioxidant.

The effectiveness of treatment was assessed by clinical and biochemical methods. Materials day of study were erythrocytes and blood plasma. The intensity of the processes of lipid peroxidation (LPO) was estimated by the concentration of malondialdehyde (MDA) in the serum. The enzymatic system antioxidative protection (AOP) was assessed by the state of the enzymes of erythrocytes catalase, superoxide dismutase (SOD), pluginindexes (SE) and plugininterface (GR).

In the course of the research it was found that when expressed clinical signs of the intensity of peroxidation processes increases. The content of MDA in patients was on average 2.5 times higher than normal (7,1 MK M/l + 2,1). Analysis of the dynamics of this indicator showed that during treatment, vkljuchajuwih is polychemie and radiation therapy in combination with "Epiphenom", the content of MDA in the blood of patients was reduced to 5.5+1.1 µm/l, and in the group not receiving "Epogen", the content of MDA was increased to 9.7+2.7 μm/L.

The study of the dynamics of activity of enzymes of antioxidant system also showed a number of features in patients of the experimental group. The group of patients not receiving "Epogen", catalase activity in erythrocytes during treatment tended to decrease from 17.2+of 2.5 to 10.4+2.1 MCAD/er. At the same time, the group of patients receiving "Epogen", she rose from 17.9+2.6 to 22,7 + 3.1 MCAD/er. Because the catalase activity is a quantitative measure of the antioxidant defenses, the results obtained indicate that the group of patients receiving "Epogen", work better mechanisms that protect cells from aggressive peroxide oxidation, primarily hydrogen peroxide. Additional indirect evidence of this fact is the increase of osmotic resistance of erythrocytes in these patients.

In turn SOD is a key enzyme of intracellular antiradical protection. It was found that during treatment the activity of SOD in erythrocytes of patients in the control group also decreased from 260+35 to 165+39 usled/mler., and experienced groupactivity SOD not only varied, but tended kJ increase with 250+25 to + 283+31 usled/mler.

Enzymes GR and GP (the chap who Atinova antiperoxidase system) when you use Epopen" more effectively protect cells against peroxide stress. These studies showed that after the standard treatment for patients of both groups the level of glutathione was below normal by about 35%. Consumption of SUPPLEMENTS "Epopen has increased the GR activity from 22.0+4,1 to 45.2+9,1 mm glut-8H/ml er. compared with control - 24,5+4,9 mm glut-8H/ml er. to 32.1+5,0 mm glut-8H/ml er. Activity GP this has increased from 10.5+1.5 to 45,6+8,5 mm glut-8H/ml er., whereas in the control it has only increased from 13.2 to+2.4 to 25.3+3,8 mm glug-8H/ml er.

These data indicate that the positive impact of the BAD "Apaven" on General non-specific oxidation resistance of the body of patients. When the consumption of Apiana" patients from the experimental group had more favorable course of the disease in General. They observed improvement of health, reduction in the number of re-exacerbation, there was a marginally stable remission, improved indicators of immunity, patients were able in time to conduct a second course of chemotherapy and radiation therapy.

Examples of other effects on cells and systems of the body.

Example 7. The effect of the drug on the living cell. The influence of composition on energoregulirovaniju isolated mitochondria of skeletal muscles of rats was carried out on the example compositions "Epopen-N" and "Epochen-N". A suspension of mitochondria isolated from skeletal muscle homogenate of the rat in the environment) is a (mol): sucrose - 0,25, MOPS is 0.01, potassium salt of ethylenediaminetetraacetic acid (CATC) of 0.002 at pH of 7.4, was placed in the incubation medium, comprising (mol)potassium chloride and 0.12, MOPS - 0,011, at pH 7.4. The mitochondrial respiration was measured by printing a cell which contained 0,004 mol of potassium glutamate as substrate oxidation, 0,0006 mol adenosine diphosphate (ADP) and 0.00005 mol of 2,4-dinitrophenol.

The influence of the composition in comparison with BHT and olivenol consumption by mitochondria oxygen under different conditions are presented in table 6.

As follows from the data of table 6, the introduction of the compositions of the causes, as in the case of olivina, strong inhibition of respiration in the 4th metabolic condition, whereas BHT has virtually no effect on this parameter.

Adding disconnector type of 2,4-dinitrophenol in this condition stimulates breathing. The obtained results indicate that the composition inhibits ATP-ABC mitochondria, with the greatest effect observed when using Epogen-N. In this case, the consumption of ATP per unit of oxygen consumed increases by approximately 70%.

Table 6

Oxygen consumption by the mitochondria of skeletal muscles of rats under various conditions
The rate of mitochondrial respirationthe control The concentration of drugs, mol ml
BHT 0.0002OlifenEpogen-NEpogen-N
V017.014.618.616.919.0
V3116.063.483.085.074.6
V446.346.622.017.216.2
VDNF86.442.755.546.742.9
DKh(V3/V4)2.511.363.864.944.60
VDNF/V41.871.132.542.722.66
V3/VDNF1.341.201.591.821.74

Example 8. The effect on the microorganisms.

In the course of the study investigated the effects of composition on the culture of microorganisms. The test crops were selected on the basis of their different sensitivity to the adverse effects of the external environment, including chemicals, due to:

type threenucleon wall (gracilicutes, Firmicutes, yeast);

- presence on the wall of the additional surface layers (capsules and other);

- the origin of the strain (Museum or clinical isolate);

- the individual characteristics of the microorganism;

the population density of microorganisms, experiencing "pressure" adverse factor.

As an additional measure took into account the identity of the test culture to normal (NM) or opportunistic (UPM) microflora, the List and characteristics of the test cultures are presented in table 7

Table 7

Characteristics of the used test cultures.
The test-cultureThe type structure of the cell wallRepresentative NM or UPMThe Museum strains or clinical isolatesResistance to the adverse effects
Escherichia coli M-17GracilicutesNMMuseumModerate
Klebsiella pneumoniaeGracilicutesUPMClinical isolatehigh (capsules)
Salmonella en-teritidisGracilicutesUPMMuseumWeak
Staphylococcus aureus 209Phi is minuty UPMMuseumModerate
Lactobacillus acidophilus D76FirmicutesHMMuseumModerate
Candida albicansYeastUPMClinical isolateHigh

Methods.

Test cultures were grown in appropriate nutrient media (Lactobacillus acidophilus in MPC-1; Escherichia coli M-17, Klebsiella pneumoniae. Salmonella enteri-tidis, Staph. aureus 209 - nutrient broth; Candida albicans - maltose broth) for 24 hours at 37°C. liquid cultures were prepared by standard suspension density W-10 CFU/ml and was applied on a 100 μl on the surface similar to agar media containing 0.025-0.5% of the studied drugs. Crops were incubated at 37°C for 5 days, watching daily then made the counting of colonies. The results were expressed in lgKOE/ml (see table 7').

Note. In the absence of growth of the colonies believed that 100 μl sample contains less than 1 colony, i.e. less than 10 colonies in 1 ml Respectively lgKOE/ml=1 correctly be represented as lgKOE/ml <1.

Table 7

Survival of microorganisms in the presence of the drug Epogen-N depending on the drug concentration and microbial density is opulatio
The culture testControlEpogen-N,%
0.0250.050.10.250.5
Escherichia coli M-17888888
777777
666665
555554
444443
533333
Klebsiella pneumoniae888211
777211
665111
554111
44311 1
632111
Salmonella enteritidis888885
666661
444441
Staphylococcus aureus 209888843
777731
666611
555511
444411
333311
Lactobacillus acidophilus D-76884311
773211
6611 11
551111
441111
331111
Candida albicans888877
777766
666655
555544
444433
333322

Example 9. The impact of the drug on animals. The study claimed compositions as feed additives was carried out in SHPK them. Lenin Bryansk region on the example of rearing cattle. The tests used a group of bulls 26-28 months of age (12 clinically healthy animals in the group) with an average live weight of 311±4,72 kg. Animals of the 1st group (control) and gruppy (experienced) received the basic diet, which was balanced on the main nutrients in accordance with generally accepted standards, but the calves of the experimental group in addition to the basic ration received Epogen-N (1 gram per head per day) and Epogen-H.

Blood samples for the study were taken in the beginning of the experiment (may 1) and July 3, before the alleged surrender of experimental animals to the slaughterhouse for slaughter, which is independent from the management of APC them. Lenin circumstances was postponed until July 26.

The dynamics of the body weight of experimental animals are given in table 8.

Table 8

Dynamics of changes in body weight of experimental calves depending on the nature of the drug
Study dateControl

group(p-12)
Experienced group Epopen N(p-12)An experienced group of Epogin N (p-12) M±t% growth Epopen N/Epopen N
M±tM±t
may 1, 2004298,33±8,42305,83±6,21308,9±6,4to 102.3/103,6.
July 3, 2004338,33±8,95358,33±5,48362,5±6,6105.9/107.2
July 25, 2004357,50±9,38375,00±6,57104.9/109.7

Example 10. The effect of the drug on the hematopoietic system and radioprotective effect of the drug is

Tests were conducted on fed on the meat of the bulls in APC them. Lenin Novozybkov district of the Bryansk region in terms of the density of soil contamination management of radioactive cesium 15-40 Ku/km2. Used group Bychkov 26-28 months of age (12 clinically healthy animals in each group) with an average live weight of 311±4,72 kg

The control group received the basic diet (RR), which were balanced for basic nutrients in accordance with generally accepted zootechnical standards. Experimental group received the PR+Epogen-N (fed 1 gram per head per day, daily for 3 months of the experiment).

We investigated the following parameters in the blood, muscle, liver, kidney, feces, and urine of experimental animals:

the concentration of peroxide oxidation of lipids (malonic dialdehyde);

the concentration of reduced glutathione (low molecular weight sulfhydryl groups);

the concentration of oxidized glutathione (low-molecular disulfide group);

the concentration of heavy metals;

complex hematological parameters, including leukogram, analyzing, reducing, adhesion, adsorption and microbicide the activity of neutrophils, the number of T - and b-lymphocytes, the activity of aspartate-notransferase and alanineaminotransferase, the activity of glutathione-transferase and glutathione peroxidase, protein concentration and its fractions, glucose, creatinine, urea;

- conducted monitoring of the radioactivity of all fed to experimental animals for feed, in vivo assessment of radioactivity animals and analysis of radioactivity pair of carcasses and deboning of carcasses after slaughter of the animals at the Bryansk meat, all feeds being fed determined the content of heavy metals.

Blood was taken three times - at the beginning, middle and end of the experiment. The analyses in the feces and urine were carried out in daily samples.

The number of leukocytes and erythrocytes in the blood was calculated in the camera Goryaeva, leukocyte formula in smears stained by Romanovsky-Institute. Phagocytic index (TN) was calculated as the percentage of neutrophils capable of uptake of latex particles, phagocytic index (PI) is the average number of latex particles, absorbed one active neutrophil, absolute phagocytosis of blood (AF, 10/l) - total number of latex particles ingested by neutrophils per liter blood [Chumachenko V.E., A. M. Vysotsky, Serdyuk N.A., Chumachenko CENTURIES the Definition of natural resistance and metabolism in farm animals. - Kiev: Vintage, 1990. - 136 C.]. Functional metabolic and the activity of neutrophils was assessed by the results of reduction reaction narasinga of tetrazole [Subic MG, Mednikova VG NBT test in children in normal and purulent bacterial infections // lab. case, 1978. No. 1. - S-666. Subic MG, I.V., Nesterov, Starchenko V.M. Test of nitrosonium tetrazolium in assessing the immunological status of children with noinoipinoy diseases // lab. case, 1980. No. 7. - S-344]. Index activation of neutrophils (IAN) was calculated according to the instructions "Recompress" on the use of nst-test set. Adsorption capacity of petrophila (FP, %, PHI, c.u., AF. 10/l) and the activity of oxidase systems (+nst, %, IAN) was evaluated in two conditions: basal (databases.) in viewsate blood stabilized by heparin, and stimulated (stim.) - once you have paid in blood samples simhasana that simulates the conditions of bacterial infection and characterized by adaptation reserves of adsorption and oxygen-dependent microbicidal ability neutrophilic granulocytes. Indicator reserve oxidase ability of neutrophils in peripheral blood (PR) was calculated by [Bakhmutov IA, MS Ulyanova to evaluate the functional activity of neutrophils in the blood of animals /veterinary medicine, 1984. No. 3. - S-69].

Kislorodozawisimae microbicides neutrophils peripheral blood was assessed by the content of cationic proteins according to the method (Robinow V.I. Application of lysosomal cationic test // veterinary medicine, 1983. No. 8. - P.30-31], calculating the average cytogenic the ski coefficient (CCS) by the formula, proposed Nasakirali [Makarevich N.A. Lysosomal cationic test to assess the level of resistance of the organism in cattle // veterinary medicine, 1988, No. 5. - P.26-28]. The content of a population of T-lymphocytes (E-ROL %) was determined using the reaction rosethorne lymphocytes with sheep red blood cells, b-lymphocytes (M-ROL, %) - with erythrocytes mouse [SU 1090409]. Subpopulations immunoregulatory T lymphocytes, mainly with genernal (E-Rollr, %) and sunrising (E-Ratc) activity - test with theophylline [Degrow W., Khaitov R.M P.M., Pinegin B.V. and others, Evaluation of the immune status of the person in mass surveys (Methodology and guidelines). - M.: Medicine, 1989. - 153 C.]. Total protein was determined refractometrically, protein fraction values method [HOWTO but the application of standard biochemical methods for blood, urine and milk in veterinary laboratories. - M.: agricultural Sciences, 1981. - 85 S.].

Determination of specific activity of Cs in the muscles of animals was conducted in PHA veterinary radiological laboratory instrument UIC "Gamma plus.

The results of studying the influence of Apiana on the content of blood cells and hemoglobin in erythrocytes of young cattle (table and 10) showed the presence of the influence of apiana on blood cell count. There was a trend to less imagenum "stress" changes in the blood picture of the experimental animals with epiphenom compared to control animals (23% less than in the control group.)

Table 9

The impact of apiana on leukogram young cattle
GroupStab neutrophils, %Segmented neutrophils, %Neutrophils, %Eosinophils, %Basophils, %
Before the start of the experiment (n=12)
0,95±0.1827,49±1,5928,44±1.718.34 per±1,220,71±0,13
After 63 days of using drugs (n=6)
control0,75±0,1824,95±of 4.4426,20+5,013,89±0,270,74±0,11
Experience0,54±015*24,40±3,3324,95±3,285,77±1,31*0,59±0,26
After 85 days of using drugs (n=3)
control4,19±0,2352,13±is 3.0856,33±3,091,03±0,440,28±0,24
Experience4,81±0,31*5,43± 6,1156,33±4,840,25±0,14*0,11±0,06
Note. * - P<0.05 with respect to control group.

Table 10

The influence of Apiana on the level in the blood of young cattle lymphocytes with fragmented nucleus (% of lymphocytes)
GroupThe number of cells with fragmented nucleus, % of the number of lymphocytes
Before the start of the experiment (n=12)
0.01
After 63 days of using drugs (n=6)
Control5,10±1,12
Epogen2,07±0,26*
After 85 days of use, at slaughter (n=3)
Control0,74±0,23*
Epogen2,01±1,36
Note. * - P<0,05.

Before the experiment, the number of cells with fragmented nuclei was very low, after 63 days of the experimental period in all experimental animals showed a significant increase in blood lymphocytes with fragmented nucleus compared with the initial period. In idimmu, this is due to the fact that experimental bulls before the start of the experimental period (and the following 2 weeks of the experimental period) received winter diet, in which the specific activity of radiocesium in fodder means ranged from 7±6.5 to 81,74±61 Bq/kg Specific activity of the muscle tissue of animals before the beginning of the experimental period, measured with a "Signal" DCS-01, ranged from 0±47 to 59±39 Bq/kg Then in the diet of animals introduced forage with higher activity radioactive caesium (300±198 Bq/kg), which resulted, apparently, to an increase in blood lymphocytes with fragmented nucleus. Used biologically active substance had a protective effect and the number of abnormal lymphocytes in the blood of the experimental animals was significantly lower than the control (see table).

Table 11

The specific activity of radiocesium in the muscle tissue of the calves (after slaughter)
IndexControl group (n=3), M±tExperimental group (n=3), M±t
Specific radioactivity, Bq/kg107,73±11,0983,13±2,7*
%% control10077
Note. * - P<0.05 compared to con the roll group.

The level of oxidase activity of blood neutrophils in basal conditions in all experimental animals before the start of the experiment corresponded to the values typical of healthy animals. However, given the high phagocytic index of neutrophils in the blood was detected in calves in basal conditions (table), it indicates failure mechanisms oxybiotic microbicides these cells.

After 63 days of the experimental period the animals of the control group the oxidase activity of blood neutrophils in basal conditions did not change significantly, but the adaptation provisions of this protective system is significantly decreased. This is evidenced by the decrease in the number of NBT-positive neutrophils in the blood and index their metabolic activation (P<0.05) after making blood samples zymosan.

The use of apiana through 63 days of the experimental period was increased compared with the control group, and with the initial period of reactivity oxybiotic neutrophil defense system (P<0,05). In animals receiving Epogen, statistically significant decreasing as the number of NBT-positive neutrophils in the blood, and index their activation after making blood samples simhasana that shows the activation of the oxidase system of neutrophils to the maximum possible for these animals) degree is the same in basal conditions.

Kislorodozawisimae microbicides of blood neutrophils, provide cationic protein (CCS), the experimental animals before the start of the experiment was high and consistent with the values of the physiological norm. In animals receiving Epogen, is set to a higher content of cationic proteins in neutrophils blood compensates for low oxybiotic microbicides of these cells. Given that the synthesis of cationic proteins is a special case of protein synthesis in the body and the highest live weight during this period was the animals of this group, Epogen can be considered as a substance that promotes activation of Poisson protein synthesis.

Table 12

The impact of apiana on the immune status (cellular level) of the body in young cattle
GroupE-ROL, %E-Rollr, VoM-ROL, %O-lymphocytes, WalterESR, mm/hour
Before the start of the experiment (n=12)
26,42±1,5931,45±3,9630,67±2,5942,92±3,03
After 63 days of using drugs (n=6)
control 49,50±2,9138,50±of 2.5131,00±1,1519,50+3,531,50±0,37
Experience55,20±2,89*39,60±to 3.6724,80±1,77*20,00±2,810,66±0,14*
After 85 days of use, at slaughter (n=3)
control45,33±4,9173,33±2,407,33±2,4047,33±to 4.410,17±0,03
Experience46,67±2,6768,17±2,83*3,17±0,93*50,17±2,200,15±0,03
Note. * - P<0.05 with respect to group 1.

The experimental animals before the start of the experiment detected is reduced, relative to normative values, the content of T-lymphocytes (E-ROL, %)represented mainly T-Generali (E-Rollr, %), and elevated levels of b-lymphocytes (M-ROL, %) and lymphocytes. After 63 days under the influence of apiana animals marked increase in the relative number of T-lymphocytes, optimizing(reducing) the level of b-lymphocytes in the blood of animals.

Table 13

The influence of apiana on the activity of glutathione peroxidase and thiol-disulfide the initial status of the organism fattening meat calves
GroupGGU-1Gap-2MDAHemoglobinLow molecular weight SH and SS
Extracellular
SHSSTDS
Control312±48545±702.89±0.41160.4±10.30.547±0.090.238±0.06to 2.29
Epogen460±61565±682.30±0.44159.3±6.50.615±0.040.201±0.053.06
% of control147104809911284134
Note:

GGU-1 - glutathioneperoxidase selectarray, µm NADP oxidized/min/g hemoglobin, the substrate is hydrogen peroxide;

Gap-2 - glutathioneperoxidase selenesetestcase (glutationtransferase), µm

NADP oxidized/min/g hemoglobin, the substrate - Gidropress tetr-butyl;

MDA - malonic dialdehyde, μm/ml plasma;

Hemoglobin - g/liter of blood;

SH - low molecular weight sulfhydryl group (glutathione restored + cysteine), μm/ml;
SS - molecular disulfide group (oxidized glutathione + cystine), μm/ml:

TDS - thiol-disulfide ratio (SH/SS).

Thioldisulfide ratio (TDS), i.e. the ratio of sulfhydryl groups to disulfide in serum is an important regulatory parameter and, at the same time, mobile diagnostic test evaluation of nonspecific resistance of the organism. It can be most informative to characterize the "buffer capacity" of the antioxidant system, as in norm and at a pathology. The dynamics and magnitude of changes in thiol-disulfide ratio (thiol-disulfide system) are a reflection of the development of adaptive reactions and allow you to directly assess the level of nonspecific resistance of the organism.

These data indicate that non-specific resistance, the buffer capacity of the antioxidant system and, consequently, adaptation and protective functions in the experimental animals were higher than in the control.

Studies have shown:

1. Across the studied complex zootechnical, hematological and physiological-biochemical parameters, gobies experimental group had an advantage over the control group.

2. The indicators characterizing the thiol-disulfide and antioxidant system (enzyme activity of glutaminergic the basics and glutationtransferase, the concentration of malondialdehyde, hemoglobin, number of reduced and oxidized glutathione), we can conclude that the enhancement of nonspecific resistance, the buffer capacity of the antioxidant system and, consequently, adaptation and protective functions in the experimental animals compared with controls. Introduction to the diet epopen had a beneficial impact on the status of protective forces of the organism of animals from the experimental group. Especially relief and significant changes in Epifanova group marked by the activity of glutathione peroxidase, the magnitude of which 47% was superior to the values inherent in the control animals. The concentration of malondialdehyde was 20% lower, which confirms the decrease in the intensity of the processes of lipid peroxidation and inhibition of the processes of excessive and harmful free radicals, i.e. Epogen works as an antioxidant.

3. As a result of increased concentrations of low molecular weight sulfhydryl groups at 12% and a simultaneous decrease of 16% low-molecular disulfide groups, thiol-disulfide ratio substantially and significantly increased by 34%. It also confirms the ability of anopen to prevent oxidative metabolic stress in the body steers. Thus, the analysis of this group of criteria also confirms the conclusion about the increase aspecific the Russian resistance, the buffer capacity of the antioxidant system and, consequently, adaptation and protective functions in the experimental animals compared with controls adding to fed diet 1 g anopen daily for 3 months.

4. According to the study, concentrations of heavy metals: lead, cadmium, selenium, copper, iron and zinc in urine, feces, blood, muscle tissue, liver and kidney of experimental animals revealed quantitative characteristics and the specifics of the changes, i.e. Epogen in the tested doses and duration of inclusion in the diet acts as an agent for reducing the content of heavy metals in the body of fattening bulls.

Example 11. The effects on adaptation indicators of the body.

Indicators of energy metabolism, lipid metabolism and antioxidant activity of the organism nonlinear white mice standard weight after 15 days of administration of substances of drugs per os daily dose of 50 mg/kg by using a dispenser with atraumatic tip is presented in table 14.

Table 14

The influence of the composition of the drug on the indicators of the functional state of the organism's adaptive systems
IndicatorsGroups of animals
Control the OlifenEpogen AndEpogen N
Body weight, g26.1±1.526.4±1.127.0±1.327.2±1.3
Total lipids, serum, g/l3.6±0.22.9±0.2*3.1±0.23.5±0.2
Cholesterol, serum, mmol/l1.64±0.441.60±0,241.62±0.311.65±0.32
The total bilirubin, serum, mmol/l3.2±0.33,0±0.42.9±0.23.0±0.2
-SHrp, serum, mg%1610±901630±401620±701650±70
Restored glutathione) liver (mg%161±8163±11164±11162±11
Glycogen, liver, mg%2420±1002400±1502450±1202480±120
Glucose, serum, mg%92±1090±1289±1390±13
Glucose, muscle, mg%145±30150±10148±40150±40
ATP, heart, mcmong 2.6±0.12.9±0.13.0±0.32.7±0.2
ATP, muscle, µmol/g5.2±0.15.5±0.45.7±0.16.8±0.3*
The intensity of tissue respiration, heart ál 02/100 mg/HR63±568±269±571±6*
The intensity of tissue respiration, muscles, ál 0^/100 mg/HR22±429±530±737±6*
* reliable differences from control at P<0.05

The presented results indicate adaptation action orientation of the studied substances, drugs, and the effect on tissue respiration effectiveness of the inventive compositions was higher than that of registered drug "Olifen".

Example 12. In the clinic of gastroenterology and pediatric surgery clinic and the Department of maxillofacial surgery, Central clinical hospital n.a. Semashko MPs were tested vitamin drinks "Civita", prepared on the basis of dry mix (bag weighing 20 g was dissolved in 200 ml of water), which includes vitamins C, b2, PP, calcium, phosphorus, natural pectin, as well as juices, raspberry, lemon or cherry, as well as 5% wt. Epogen-N or Epochs is h-H

Distribution of patients according to nosology, which in addition to the basic therapy and surgical intervention was appointed an additional drink "Civita", presented in tabl.

Table 15

The nosology of patients who took the drug "Civita"
Drug and clinicThe nosologyThe number of patients
Gastroenterology "Zevita with Epogen-H"Peptic ulcer disease localized in the stomach3
Cirrhosis of the liver8
Chronic recurrent pancreatitis12
Peptic ulcer disease localized in 12-dispersed intestine9
Surgical pathology "Zevita with Epogen-H"Pancreonecrosis. Abscess retroperitoneal space5
Cancer of the pancreatic head. Mechanical yolk14
Intestinal fistula3
Stomach cancer35
JCB, chronic calculous cholecystitis52
Oral and maxillofacial surgery "Zevita with Epopen"Inflammatory diseases of maxillofacial area (abscesses, f is agony, lymphadenitis)37
Fractures of the bones of the facial skull15
Bone-reconstructive surgery of the facial skull (osteotomy, bone grafting)11
Only204

Gastroenterological patients "Zevita-Epogen" simultaneously with the basic therapy was administered in the diet was expanded to table No. 5 Pevzner. The duration of taking the drug was not less than 7 days and throughout hospitalization, and subsequent recommendation seasonally course 2-week admission as adaptogene in the form of an aqueous solution 2-3 times a day before meals. Carestream patients were recommended to take the drug when the weather changes.

Ill surgical profile of the drug "Zevita-Epogen"was administered according to the following scheme (depending on the volume of transactions)

Biliodigestive anastomoses
Table 16

Regimen drink "Civita"
The volume of operations- Appointment in the postoperative period (days)- The duration of the drug
Gastrectomy410 days
Subtotala resection

stomach
410 days
314 days
Laparoscopica cholecystectomy27 days
Oral and maxillofacial surgery37 days three times a day

From subjective indicators: the majority of patients reported improvement in overall health, comfort, normalization of appetite.

From objective indicators; in patients with postoperative noted earlier normalization of blood counts and urine; which is directly correlated with the reduction in the duration and volume injected infusion solutions. It was noted earlier activation of the sick. In patients operated on for mechanical jaundice was noted early leveling symptoms of endogenous intoxication, manifested normalization of biochemical parameters of blood.

Patients operated with a diagnosis of cancer of the stomach (gastrectomy and Subtotal gastrectomy), noted the emergence of appetite on the second day after starting the drug.

A special group of cancer patients was 26 patients before surgery, during the survey period, were given "Zevita-Epogen". Further surgery of these 22 patients in the postoperative period was continued for 4-6 days after surgery the drug as in the preoperative period, and in the postoperative period of patients was marked improvement in appetite, increase efficiency.

When maxillo-facial surgery there has been more rapid normalization of the indicators, earlier reduced toxicity and more rapid recovery of microcirculation in the area of inflammation.

On the basis of the conducted research it can be concluded that the drugs "Civita" it has high biological activity, can be used in surgical practice for treatment on a background of basic therapy and surgical intervention as a drug that has a common antioxidant, antihypoxic, immunomodulation, desegregated and stimulating erythropoiesis in patients with acute pancreatitis, pancreatic necrosis, as well as in the pre - and postoperative period in patients with gastric cancer, biliopankreatoduodenalnyj zone and other surgical pathology, as well as in gastroenterological practice for the treatment of patients with gastric ulcer and duodenal ulcer, cirrhosis of the liver.

Example 13. The effect of the drug on the cardiovascular system

Drug Epogen-N was introduced into the chocolate mixture before formation of the chocolate in the amount of 0.15% of the total weight. Obtained after the formation of a chocolate bar "Extreme" weight 35 g contained 11% white is s, 60% carbohydrates, 19% fat, 1.5% lactulose, 1% of calcium salts, 0, 15% of apiana, as well as vitamins and flavoring. Were surveyed 20 people. Assessment of severity of symptoms and risk factors was conducted on a point system:

- 5-7 points - the probability of coronary risk "very low";

- 8-9 - "low";

10-12 points - "probable";

- over 12 "high."

Of the risk factors noted:

- 1 person - obesity of 1-St degree, exogenous constitutional form, BMI (body mass index) over 30;

- 3 people - overweight, BMI 25 to 30;

- 12 people - lack of exercise, all studied sports did not physical exercise irregular;

- 4 people - Smoking;

- 2 people - quit Smoking less than one year.

According to the survey results, four people had established diagnoses: "atherosclerosis of the aorta, atherosclerotic cardiosclerosis, the initial manifestations of atherosclerosis of cerebral vessels" (the diagnosis was confirmed data, chest x-rays in the form of a seal of the aorta, ECG changes (reduction of the T wave, the disturbance of intraventricular conduction, various blockade, WPW syndrome and others), lipid metabolism disorders).

In addition to the above persons, four people had changes of lipid metabolism in the form of increase of level of cholesterol, triglyceride, lipoprotein tightly the tee. Eight people surveyed had high blood pressure, as the BPA, and ADD.

In the second stage, within one month of the tested group daily took 1-2 bars "Extreme-X". At the end of the period of study, all individuals were made of the control ECG, biochemical blood tests (lipids, cholesterol). During the month were recorded daily HELL. Analysis of the results showed that:

- six people flying personnel normalized ECG (restored tooth T, improved intraventricular conduction);

- eight subjects there was a correction of lipid metabolism (lowering cholesterol, low density lipoprotein, is normalized in the atherogenicity);

happened normalization and stabilization of HELL;

- took place before taking SUPPLEMENTS severe dysfunction in the form of fatigue, tiredness, poor sleep, increased sweating decreased significantly.

The severity of symptoms and risk factors of atherosclerosis before and after taking SUPPLEMENTS is shown in table 17

Table 17

The effects of taking BAD "Extreme-X" on the severity of the signs and risk factors for atherosclerosis
SeverityOccupancy before the treatment Occupancy after treatment
very low11
low13
probable47
high61

Example 14. The effect of the drug on the cardiovascular system. In the clinic Flight test Institute named after M.M. Gromov when conducting functional tests in the interests of the medical and flight examination conducted studies of the cardiovascular system flight personnel.

To describe the state of the subject was used IN the indicator, which reflects the degree of tension of regulatory mechanisms of the organism, the level of centralization of management circulation.

The conditional volatility of values IN from 5 to 500 usled

IN<30 usled - vagotonic; JN=30-90 c.u - Eutopia; JN=90-160 used - sympathicotomy; IN>160 usled - hypersympathicotonia.

The survey revealed 108 cases of dystonia: 20 people with a predominance of vagotonia; 70 people with sympathicotonia; 38 people with hypersympathicotonia.

30 patients with manifestations of hypersympathicotonia during the month in addition to the basic diet, took SUPPLEMENTS "Extreme" 2 times a day on 1 bar with weight 35 g (BAA before Talal a chocolate mixture, containing 0.15 wt.%. the song "Epopen-N").

Analysis of the survey flight personnel taking dietary SUPPLEMENTS as "Extreme"on the subjective self-assessment of functional status after completion of a cycle of taking SUPPLEMENTS showed that 96% of patients gave a positive assessment of the proposed tool, optimization and maintenance. It was noted the decline of domestic tension, reduce sleepiness and fatigue. In the process of using the SUPPLEMENTS "Extreme", there were no allergic reactions and digestive disorders with the admission of the proposed tools.

After a month of taking SUPPLEMENTS "Extreme" flight composition having a diagnosis of autonomic neuropathy, conducted a test with a continuous speed-increasing load on the bike (300 KGM, 600 KGM, 900 KGM) with continuous ECG in 12 leads. It was determined the type of hemodynamics: akineticheskie, Hypo - and hyperkinetic, as well as the adequacy of the increase of blood pressure (BP) and heart rate in relation to the load. Calculated a number of options to help early diagnosis of coronary heart disease (CHD), vegetative-vascular dystonia (VVD): double product (DP), where DP=mahcs×Adesto.×10; index energy costs (EEZ), where the EEZ=DP/100×W-, where w is the amount of work done on the bike.

Diagnostic difficulty identified what I disorders of autonomic regulation used method of registration sinus heart rhythm cardiointervalography (CIG) with subsequent mathematical analysis of the structure. Kardiointervalogrammy is a continuous recording of at least 100 consecutive cardiocycle intervals (R-R) in one of the electrocardiographic leads. The results are shown in table.

Table 18

Influence of the nature of dietary supplements on the body if IRR
Qty PACVEMJOHNDPEEZ
Before takingAfter takingBefore takingAfter takingBefore taking SUPPLEMENTSAfter takingBefore taking SUPPLEMENTSAfter taking
305700 KGM5700 KGM160-240 ed70-90%270300the 4.5-5.6±0.33.6±0,2

Example. 15. The influence of composition on the autonomic nervous system (ANS) was estimated on the basis of application of chocolate bars BAD "Extreme"

Drug Epogen-N was introduced into the chocolate mixture before formation of the chocolate in the amount of 0.15% of the total weight. Obtained settlement is e formation of a chocolate bar BAD "Extreme" weight 35 g contains 11% protein, 60% carbohydrates,19% fat, 1.5% lactulose, 1% of calcium salts, 0, 15% of apiana, as well as vitamin and flavorings.

The tests were carried out on 42 human flight personnel to optimise their functional capacity and improve efficiency.

Assessment of autonomic dysfunction and the severity was carried out according to a points system: - light - 3-5 symptoms, moderate - 6-10 symptoms expressed more than 10 symptoms.

The prevailing tone of the autonomic nervous system (ANS) recorded: vagotonic - number parasympathetic symptoms exceeds the number of sympathetic on 2 or more; sympathicotonia - number of sympathetic symptoms exceeds the number parasympathetic for 2 or more; normotone - the ratio of the sympathetic and parasympathetic symptoms does not exceed one.

Within 12-14 days of the study group took SUPPLEMENTS "Extreme" in the form of a single bar with weight 35 grams in the middle of executing flight missions. After completion of the research programme again on investigational was filled application Form status of the autonomic nervous system after taking SUPPLEMENTS, on the basis of which assessed the state of the ANS. The results are shown in table 19.

Table 19.

The effect of nutritional Supplement on the state of the GHS
IndexA number of people
Before takingAfter taking
The degree of autonomic dysfunctionLight820
Moderate2014
Pronounced149
The prevailing tone of the ANSVagotonic2612
Sympathicotonia1210
Normotone420

In the analysis of 42 questionnaires completed before taking SUPPLEMENTS, drew attention to the changes of Central hemodynamics in the development geodinamicheskih manifestations - lowering activity of cardiac activity (decrease in heart rate and IN), accompanied by a decrease in cardiac output and, consequently, decrease the BPA and growth ADD, the lower the NPV and TT.

That is, there is a decrease in the overall autonomic tone and energy processes, dominated by a pronounced degree of autonomic dysfunction, and the prevailing tone of the autonomic system is vagotonic.

The analysis of the questionnaires on the evaluation of the subjective state before using the SUPPLEMENTS showed that:

- 50% of the study had impaired the value of sleep as difficulty falling asleep and disturbing sleep with frequent prosypaniem;

- 35% - noted change the complexion (pale or red, reinforced vascular pattern);

- 20% had various allergic reactions;

- 60% had expressed sweating or, on the contrary, dry skin;

- 70-80% felt General weakness, fatigue, internal stress, depression or unmotivated anxiety.

After two weeks of taking SUPPLEMENTS Extreme majority who indicated an improvement in their General condition, normalization of sleep, mood, improve efficiency, attention, memory. As well as decreased hyperhidrosis, improved complexion.

The parameters of Central hemodynamics (HR, CS, DT,...) and energy metabolism (NPV, TT) has long been stabilization in the direction of normalization, resulting in a changed degree of autonomic dysfunction has become the predominant light, and the prevailing tone of the ANS was normotone.

Table 20

The effect of the drug on the status of the SNA
IndexBefore flightAfter flying
ExperienceControlExperienceControl
Systolic blood pressure (SBP)135140/td> 120105
Diastolic blood pressure (ADD)90907086
The frequency of respiratory movements (NPV)18.519.51713
Body temperature (TT)36.836.936.536.0
Heart rate (HR)80926854
The tension index751284434

If before the flight there was a merger of the sympathetic nervous system as a response to an extreme situation, the drug during the flight contributes to the restoration of physiological parameters to normal levels, which was not observed in the control group, which was dominated by the phenomenon of reduction of autonomic tone and energy metabolism.

Thus, MTIWP decreases the activity level of the physiological functions of the cardiovascular and respiratory systems, the overall autonomic tone and provides the intensification of energy processes, which is very important in flight work if necessary emergency actions.

This stabilization of the overall autonomic tone when using the SUPPLEMENTS "Extreme" is associated with the activation of Central regulatory mechanisms of the autonomic nervous system, oxygenation, tissue respiration functional components of dietary SUPPLEMENTS.

Example 16. The effect of the drug on the immune system of the body. Clinical trials EPOGEN-a in patients with purulent surgical infection was conducted in the Department of purulent surgery, Central clinical hospital. N. A. Semashko the Ministry of Railways of the Russian Federation on the basis of the Department of surgical diseases and new endosurgical technologies of the Moscow state medico-stomatological Institute.

Epopen was applied in powder form to 0.5 g for oral administration. The course of treatment was 10 days.

At admission all patients underwent examination according to the standard scheme, was prescribed a comprehensive treatment aimed at the normalization of metabolism and homeostasis, the correction of immune status, resolution perifocal inflammatory changes in the tissues, cleansing of the wound and its healing. The treatment was carried out in conjunction with already established methods of surface treatment of ulcers (wounds) low-frequency ultrasound, vacuum, stage mechanical necrectomy and treatment of wounds and surrounding tissue by infrared laser radiation. This was done by a comparative study of the effectiveness of apiana on the results of treatment of representative groups of patients according to the size and depth of ulcers (wounds), intensity perifocal the inflammation and the severity of microcirculatory disorders. Epogen used in the treatment of 67 patients aged from 22 to 85 years, including 39 women and 28 men, who formed the core group. The comparison group consisted of 70 patients whose treatment was carried out by traditional methods.

51 (76.1%of patients on the day of admission or after a brief preoperative preparation was carried out surgical treatment of purulent-necrotic lesion. In a further step how agressively to debride were performed in 10 patients. Local treatment was carried out using a combination of immobilized enzymes and 0.5% sodium hypochlorite solution, the treatment of wounds by low-frequency ultrasound, high-frequency laser radiation.

Analysis of objective data in the groups studied showed the following. In the main group the symptoms of intoxication were stopped by 2.1-1.3 days (comparison group - 4.1±1.4 days), the normalization of the temperature gradient was 4.4±1.5 days (group comparison - 5.5±2.1 days), the cleansing of wounds on 8,9±1.7 days (comparison group - 12.6±1.8 days), discharge to home 12.3±1.3 days (comparison group - 16.4±1.2 days).

Research laboratory blood parameters before and after treatment with a drug which showed improvement of hemoglobin level on 11±0.8 g/l in 52 (77.6 per cent) patients in the main group. In the comparison group decreased levels of hemoglobin in an average 6± 1.3 g/l in 28 (40%) patients.

Cancellation of antibacterial drugs in the study group was carried out by 5.1±1,3 night, while in the control group on 8,31±1,1 night.

The study of the immune status showed that 10 days of treatment the number of T-lymphocytes in patients of the main group reached norms (64,1±1,1%), a marked increase in the number of T-helper cells (57,5±1,1%) and reduction of T-suppressors (7,2±1,5%). Patients of the control group the number of T-lymphocytes was lower (56, 4mm±1,7%); the number of T-helper cells was 53.4±1,4, and the number of T-suppressors - 9,9±1,8%.

Thus, according to immunological examination of the patients revealed a pronounced immunomodulatory effect after treatment with epiphenom in patients of the main group compared with the control group.

The assessment of the degree of toxemia was carried out on indicators leukocyte index of intoxication using the formula Jail-Khalifa. The assessment of the degree of toxemia showed complete normalization of leukocyte index of intoxication in 58 (86,6%) patients of the main subgroups (1.00 srvc. units), while remaining at an average of 1.42±0,21 used indicator of leukocyte index of intoxication in the comparison group 64 (91.4 per cent) testified to the preservation of the syndrome of endogenous intoxication.

Allergic reactions side is Astia of epopen in the research process have been identified. Contraindications to the use of the drug was not detected.

The inclusion of epopen in the complex therapy of patients with abscesses and phlegmon of different localization, infected wounds provides influence on the basic mechanisms of disease and has a positive effect on humoral and cellular immunity, increase nonspecific resistance, the course of reparative processes. Combination therapy using epopen allows to reduce the duration of antibiotic therapy by 3.2 days and, thus, the consumption of expensive antimicrobial drugs, and the period of inpatient treatment - 4.1 day.

Studies have shown that the inventive composition provides a broad positive impact on the livelihoods of the body, in particular is a promising radioprotector and anticancer drug.

1. Pharmaceutical agent based on polyoxyethylene ether, characterized in that it additionally contains hydroquinone when the mass ratio between polyoxyethylene ether : hydroquinone from 83:17 to 5:95.

2. The tool according to claim 1, having a combined antioxidant, antihypoxant, anticancer, radioprotective, immunostimulant and biocidal action.

3. The tool according to claim 1, characterized in that as polio sierranevada ether it contains 2-(1-hydroxy-4-hydroxyphenyl) benzoquinone.

4. The tool according to claim 1, characterized in that as polyoxyethylene ether it contains products grinding 2-(1-hydroxy-4-hydroxyphenyl) of benzoquinone to hydroquinone.

5. The tool according to claim 1, characterized in that as polyoxyethylene ether it contains 4-hydroxyphenyl-2,4-dioxobenzo.

6. The tool according to claim 1, characterized in that as polyoxyethylene ether it contains products grinding 4-hydroxyphenyl-2,4-dioxobenzo with hydroquinone.

7. The method of obtaining the means according to claim 1, which consists in the fact that polyoxyethylene ether is mixed with hydroquinone and the resulting mixture fray until a homogeneous mass.



 

Same patents:

FIELD: medicine, surgery.

SUBSTANCE: on the 1st d after operation a patient should be injected with mexidol intravenously by drops at the dosage of 300 mg, during the next 2 d mexidol should be injected intramuscularly twice daily at the dosage of 200 mg. Moreover, during 10 d after operation a patient should be perorally introduced with ADP-37 preparation a the dosage of 6 capsules daily and during 5 d one should affect the wound with impulse magnetic field at about 0.5-1.0 Tl intensity through Dalcex-trypsin filter cloth impregnated with 0.01%-serotonin solution, once daily. The innovation enables to accelerate the terms of wound healing up to 6-7 d and avoid therapy-induced complications.

EFFECT: higher efficiency of therapy.

1 ex

FIELD: medicine, surgery.

SUBSTANCE: the present innovation deals with treating osseous gunshot fractures due to fixing osseous fragments with the help of the apparatus of extrafocal osteosynthesis followed by their reposition and surgical treatment of the wound. After surgical treatment on the 1st d after operation a patient should be intravenously injected with mexidol by drops at the dosage of 300 mg once daily, and during the next 2 d - intramuscularly twice daily at the dosage of 200 mg, moreover during 10 d after surgical treatment a patient should be perorally introduced with ADP-37 at the dosage of 6 capsules daily and during 5 d it is necessary to affect the wound with impulse magnetic filed of 0.5-1.0 Tl intensity through Dalcex-trypsin filter cloth impregnated with 0.01%-serotonin solution in physiological solution once daily. The innovation enables to accelerate the terms for wounds healing, avoid complications due to complex pathogenetic approach during therapy conducted.

EFFECT: higher efficiency of therapy.

2 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to medicinal agent effecting on the immune system. Medicinal preparation comprises 5-amino-2,3-dihydro-1,4-phthalzinedione lithium or potassium salt. Preparations possess the antitumor and antioxidant effect. The developed variants of the medicinal preparation distinct by duration and spectrum of effect and by pharmacokinetic indices and depending on their purity they can be used in oral and intramuscular administration and for other medicinal procedures.

EFFECT: valuable medicinal properties of preparation.

6 cl, 3 tbl, 4 dwg, 12 ex

FIELD: chemical-pharmaceutical industry.

SUBSTANCE: the present innovation deals with creating preparations being of antioxidant activity. It has been suggested the application of 5%-aqueous extract out of wild rosemary sprouts (Astragalus dasyanthus) as an antioxidant preparation. It has been of pronounced antioxidant action and could widen the number of antioxidant remedies of natural origin.

EFFECT: higher efficiency of application.

18 dwg, 2 tbl

FIELD: medicine, clinical pharmacology, restoring therapy.

SUBSTANCE: the suggested preparation is being a lipid fraction isolated out of a king crab's liver Paralithodes comtschatica that contains 10% polyunsaturated fatty acids, 10% alkyl-diacyl glycerides and the complex of natural bioantioxidants being of highly correcting, hypocoagulative and antioxidant properties. The preparation suggested enables to widen the quantity of food BAA of natural origin of lipid-correcting action at pronounced hypocoagulative and antioxidant properties based upon application of natural lipid complex. It could be applied as an efficient means of prophylaxis of cardio-vascular diseases and other pathologies, when lipid exchange is broken and which is accompanied with disorders of hemocoagulation and intensification of lipoperoxidation process.

EFFECT: higher efficiency.

1 ex, 4 tbl

FIELD: medicine.

SUBSTANCE: the suggested compound being 3,6-dioxocyclohexa-1,4-dien-1,2,4,5-sodium tetra-sulfonate is of antihypoxic and cytoprotector action. Moreover, the composition has been suggested being of anti-grippe action. The composition declared includes remantadin and 3,6-dioxocyclohexa-1,4-dien-1,2,4,5- sodium tetrasulfonate.

EFFECT: the compound mentioned enables to decrease remantadin toxicity during its usage at high dosage during treating the grippe infection.

4 cl, 6 dwg

FIELD: medicine, surgery.

SUBSTANCE: the present innovation deals with preventing purulent-septic complications in early post-surgical period at surgical treatment of gangrene-complicated ischemic foot form. During 3-5 d before operation and during 7-8 d after it one should introduce perorally ADP-37 preparations for patients at the dosage of 6 capsules daily followed by intramuscular injection of mexidol immediately after operation at the dosage of 2.1 mg/kg body weight, and during the next 3 d - at the same dosage every 12 h. Surgical wound should be treated with a gel that contains 2%-mexidol followed by affecting the wound with impulse magnetic field at 0.5-1.0 Tl intensity.

EFFECT: the innovation enables to prevent the development of purulent complications, stimulate reparative process, reconstruct the structure and the functioning of microcirculatory system in limb's soft tissues.

2 ex

FIELD: pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to an agent possessing antioxidant activity. Agent possessing antioxidant activity and containing water-soluble lignin is prepared from the natural vegetable raw. Water-soluble lignin is isolated by treatment of lignin-containing raw with aqueous dioxane in the presence of HCl at the boiling point followed by treatment of dioxane-lignin with alkali solution up to its complete dissolving, infusion of alkaline solution with cation-exchange resin up to a definite pH value. Agent prepared by above described method from lignin-containing vegetable raw possesses the high antioxidant activity.

EFFECT: valuable property of agent, improved preparing method.

2 tbl, 2 dwg, 10 ex

FIELD: medicine, anesthesiology.

SUBSTANCE: method involves using the preparation 2-ethyl-6-methyl-3-oxypyridine succinate in preparing to anesthesia, during the total anesthesia and in post-narcosis period. Invention provides reducing risk in development of such complications as rhythm disorder, hemodynamics instability, myocardium ischemia, encephalopathy based on eliciting complex properties of the preparation - decreasing requirement of tissues with oxygen, optimization of energetic metabolism and antioxidant properties. Invention can be used for reducing risk in development of complications after the total narcosis.

EFFECT: valuable medicinal properties of preparation.

1 tbl, 2 ex

FIELD: pharmacy, chemical technology, medicine.

SUBSTANCE: invention proposes a composition that comprises 6-decaprenyl-2,3-dimethoxy-5-methyl-1,4-benzoquinone as an active component, antioxidant, non-ionogenic surface-active substance, preserving agent, lipid-soluble stabilizing agent of emulsion, water-soluble stabilizing of emulsion and water. Method for preparing the indicated composition involves mixing the definite amounts of non-ionogenic surface-active substance with antioxidant, heating to temperature 40-120°C, dissolving the necessary amounts of lipid-soluble stabilizing agent of emulsion and 6-decaprenyl-2,3-dimethoxy-5-methyl-1,4-benzoquinone are dissolved in the prepared solution. The prepared mixture is added at intensive stirring to the mixed solution of water-soluble stabilizing agent of emulsion and preserving agent in water preliminary heated to temperature 30-100°C. Invention provides improving bioavailability and increasing storage time of the composition. Proposed composition is used in prophylaxis and treatment of different diseases and for recreating the working ability.

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

2 cl, 1 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: claimed adsorbent contains spherical activated carbon having size diameter of 0.01-1 mm, specific surface determined in accordance to Langmuir equation of 1000 m2/g or more, ratio of diffraction intensities R of 1.4 or more (R is determined as R = (I15-I35)/(I24-I35) (1), wherein I15 is diffraction intensity at diffraction angle (2θ) of X-ray diffraction is 15°C; I35 is diffraction intensity at diffraction angle (2θ) of X-ray diffraction is 35°C; I24 is diffraction intensity at diffraction angle (2θ) of X-ray diffraction is 24°C), and pore volume having diameter of 7.5-15000 nm is less than 0.25 mg/ml. In another embodiment claimed adsorbent contains abovementioned spherical activated carbon with modified surface. Also disclosed are pharmaceutical composition and method for prevention or treatment of kidney or liver diseases containing said adsorbent.

EFFECT: new adsorbent for peroral administration.

20 cl, 5 ex, 2 tbl, 12 dwg

FIELD: organic chemistry, medicine, hepatology.

SUBSTANCE: invention relates to using 2-methylthiopyrimido[4,5-b]indole of the formula (1): showing melting point at 243°C (with decomposition) and value LD50 > 1000 mg/kg used in liver protection from poisoning with carbon tetrachloride. Proposed compound exceeds activity of the "Essentiale" as a comparison preparation.

EFFECT: valuable medicinal property of compound, enhanced effectiveness.

1 tbl

FIELD: pharmaceutical industry.

SUBSTANCE: claimed adsorbent contains spherical active carbon, obtained from thermosetting resin as carbon source, having particle size of 0.001-1 mm, specific surface determined by Langmuir adsorption equation of 1000 m2/g or more and pore volume of 7.5-15000 nm in diameter less than 0.25 ml/g. Also disclosed is adsorbent being similar to abovementioned one, wherein total content of acidic groups is 0.40-1.00 meq/g; total content of basic groups is 0.4-1.1 meq/g. Pharmaceutical compositions contain said adsorbents and pharmaceutically acceptable carriers and recipients. Agents of present invention are useful in treatment of kidney or liver diseases or disorders associated with uremic substance by administration of said adsorbents.

EFFECT: products of increased selectivity.

21 cl, 5 ex, 2 tbl, 11 dwg

FIELD: chemical and pharmacological industry.

SUBSTANCE: invention relates to encapsulated form of Acyzol containing Acyzol and pharmaceutically acceptable fillers in specific component ratio.

EFFECT: encapsulated mass with high technological characteristics, high biological availability and effectiveness of Acyzol component.

5 tbl, 3 dwg

FIELD: veterinary science.

SUBSTANCE: in case of dioxine intoxication animals should be prescribed with dimephosphon at the dosage of about 50-150 mg/kg body weight daily for 10-30 d. The innovation provides decreased embryonic lethality in animals.

EFFECT: higher efficiency of therapy.

3 ex, 1 tbl

FIELD: medicine, toxicology.

SUBSTANCE: invention proposes applying 15% aqueous solution of 1-methyl-5-[2'-(benzyldimethylammonio)ethyl]carbamoyl pyridinium-2-aldoxime dichloride that exceeds the 15% solution of dipiroxime (TMB-4, trimedoxime bromide) used in native medicinal practice by the curative effectiveness. Invention can be used in urgent treatment of acute poisoning with organophosphorus poisonous substances eliciting neuroparalytic effect.

EFFECT: enhanced effectiveness, valuable medicinal properties of agent.

3 tbl

The invention relates to the field of organic chemistry and medicine and relates to a derivative of imidazo-[1,2-a]-benzimidazole, specifically: 9-diethylaminoethyl-2-(3,4-dioksifenil)-imidazo-[1,2-a]-benzimidazole of dihydrobromide formula (I) providing cerebroprotective effect in radiation damage

The invention relates to organic chemistry, in particular to derive SIM-triazine-2-ethylamino-4-piperidyl-6-[(4’-methylcarbamyl-5’-methyl-1’,2’,3’,-triazole)-1-yl]-1,3,5-triazine structure:

as an antidote from fetotoksicheskoe action of the herbicide 2,4 - dichlorophenoxyacetic acid on the sunflower sprouts
Drug // 2229882
The invention relates to a new combination drug, which can be used as a means of protecting the person from the early transient incapacitation and edema of the primary reaction to radiation

The invention relates to new stable crystalline calcium or magnesium salts of (6R,S),(6S) - or (6R)-tetrahydrofolate acid, method for their production and pharmaceutical compositions based on them

FIELD: organic chemistry, pharmaceuticals.

SUBSTANCE: invention relates to compounds of general formula I and pharmaceutically acceptable salt thereof, wherein R1, R3, R4, R5, and R10 are independently H, halogen, C1-C4-alkyl, etc.; R2 is H, halogen, NO2, etc.; R6 is H, C1-C6-alkyl, C1-C6-alkoxy-substituted C1-C4-alkyl, etc.; R7 is H, C1-C4-alkyl or C2-C4-alkenyl, optionally substituted with halogen; R8 and R9 are H, R11 and R12; meanings of the rest substituents are as define in specification.

EFFECT: new compounds with value biological properties and useful as drug having activity in relates to progesterone receptor.

15 cl, 3 tbl, 80 ex

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