Agent having adaptogenic and immunomodulating activity
SUBSTANCE: agent, having adaptogenic and immunomodulating activity, containing medicinal marigold flower heads; rhaponticum carthamoides root and rhizome; horse-heal rhizome; nutmeg fruit; cardamom fruit; calamus root; sweet weed root; ginger rhizome; knotgrass; cinnamon bark; pomegranate; long red pepper; juniper fruit; leather bergenia black leaves; chitosan, taken in a defined amount.
EFFECT: agent has marked adaptogenic and immunomodulating activity.
The invention relates to the pharmaceutical industry and relates to the creation of herbal remedies with adaptogenic and immunomodulatory activity.
Domestic medical science has formulated the following requirements for adaptogenic drugs: an adaptogen should be harmless to exercise its adaptogenic effect only on the background, increasing the resistance to the harmful effects of a wide set of factors of physical, chemical and biological nature; must have a normalizing action irrespective of the direction of previous changes, and action adaptogene should be the more pronounced, the more profound adverse changes in the organism [Shabanov P.D. Adaptogens and antihypoxants // Reviews in clinical pharmacology and drug therapy. - 2003. - Vol.2. No. 3. - P.50-80].
Based on the study of literature data on the chemical composition, pharmacological properties of individual plants, we have developed a formulation of a composition consisting of 15 components (provisional title - Adaptivit). Closest to Adaptivity on the composition of plant components are prototype - a phytocomplex with adaptogenic action, representing 40% alcohol tincture of calendula blossoms, fruits of nutmeg, roots and rhizomes of Rhaponticum carthamoides, elecampane, ginger, and the marsh RA, the Ural licorice, Rhodiola rosea, bergenia, parsley, sprouts consisting of five leaves Kuril, leaves of nettle, of sea-buckthorn berries, black pepper, hawthorn [Patent RU 2259840 C 2, 10.09.2005]. The problem to which the invention is directed, is to create medicines that possess adaptogenic and immunomodulatory activity and represent the means obtained from the chopped vegetable mixture and chitosan of the following composition (parts by weight): inflorescence calendula - 13; the roots of leuzea - 13; pomegranates - 11,5; cardamom fruit - 9,0; roots of elecampane - 7,0; the fruit of long pepper - 6.5; the fruit of Juniperus communis l - 5,0; the roots of the marshmallow - 5,0; calamus roots of marsh - 5,0; grass knotweed - 5,0; the fruit of the nutmeg - 5,0; rhizomes of ginger this - 4,5; bark cinnamon (cinnamon) - 4,5; leaves black bergenia tolstolistnogo - 3,0; chitosan - 3,0.
To prepare 1000 g of the proposed means 133 g of inflorescences calendula, 133 g of roots of leuzea, 113 g of pomegranate, 92 g of fruit cardamom, 71 g of the roots of elecampane, 66 g of the fruit of long pepper, 51 g juniper berries, 51 g of the roots of the marshmallow, 51 g calamus roots of marsh, 51 g of grass knotweed, 51 g of fruit nutmeg, 46 g rhizomes of ginger, 46 g of cinnamon, 31 g of the leaf and stalk the black bergenia tolstolistnogo, 31 g of chitosan is mixed, ground in a mill to a particle size of 0.5-1.0 mm sieved through sieve No. 2 and weighed. The loss of raw materials during grinding should not exceed 2%.
To prove the validity of the proposed structure, the authors conducted a series of experiments, data which confirm its strong effectiveness. The technical result obtained by carrying out the invention, is expressed in the expansion of the range of herbal medicines with a wide range of pharmacological actions to improve the body's resistance to the influence of extreme factors of different nature.
For the experiments used vegetable raw materials and chitosan purchased in pharmacies. Pomegranate fruits and dry powders of food spices - ginger, pepper, cardamom, pepper, ground cinnamon, nutmeg powder (manufacturer, LLC Novosibirsk food plant") acquired in a trade network. Quantitative determination of the major groups of biologically active substances in the tool performed as described in the literature methods. The results of the experiments are shown in table 1.
|The content of biologically active substances in Adaptivity||No.||Name||Content (min-max)|
|1||Essential oils, in %||0,83-1,70|
|2||Carotenoids in terms of β-carotene, mg%||of 0.54-1.20|
in terms of oleanolic acid %
|4||Tannins, in terms of tannin, %||of 1.23 to 1.31|
|5||Anthocyanins, in terms of|
the cyanidin-3,5-diglucoside, %
|6||Flavonoids, rutin, %||0,47-0,62|
|7||Free amino acids|
in terms of glutamic acid, %
|0.14 to 0.31 in|
|8||Water-soluble polysaccharides, %||13,14-18,25|
Qualitative and quantitative composition of some substances in the samples defined is whether by HPLC-MS, using high-performance liquid chromatograph brand Agilent 1200", with tandem mass-spectrometric detector "ion trap" 6330, the way in which the ionization electrospray. Column Eclipse Bond C18, 5 μm, of 4.6*150 mm, Elution was performed in gradient mode, as the mobile phase used a mixture of 0.1% formic acid and acetonitrile in the ratio(1:0, 1:9, 9:1). The volume flow rate of eluent - 1.0 ml/min, volume of injected sample 10 ál of the elution time of 30 minutes. The analysis was carried out under the registration regime of negative ions, total ion current, TIC, mass discharge characteristic (MS) and child (MS2) negative ion mode UltraScan 50-1300 m/z, AutoMS. Standard samples of compounds (quercetin, rutin, luteolin, luteolin-7-glucoside, Gallic acid) was prepared at a concentration of 10 μg/ml In the chromatograph was introduced on 20 µl sample solution and standard solution samples were chromatographically in the above conditions.
Quantitative determination of ecdysone by the method of absolute calibration is performed on the chromatograph GILSTON, model 305 (producer - France); the manual injector, a RHEODYNE model 7125 (USA) with subsequent computer processing of the results of the study using Multirom for "Windows". As stationary phase was used metal column 4.6×250 mm Kromasil C18, R is Merom particles 5 microns, as the mobile phase methanol-water-phosphoric-to-one (40:60:0.5 in). The feed rate of eluent - 0.8 ml/min, time - 50 min, detection was carried out using a UV-detector "GILSTON" UV/VIS model 151, at a wavelength of 242 nm. Data analyses are given in table 2.
|The contents of the individual substances in Adaptivity (HPLC method)|
|No.||Name||Rt, min||Content Adaptivity|
|2||Quercetin, ug/g||to 12.0||122,43|
|4||Gallic acid, μg/g||1,9||8,062|
|Note: Rt- retention time|
1. The study of adaptogenic activity of Adaptivity during intense physical activity.
The experiments were carried out on white Wistar rats of both sexes weighing 180-220 g General physical endurance was determined by the conventional method and duration of swimming animals in the pool with cargo, amounting to 7% of body weight [Redsamara, Iiankulova, Apetito. Adaptogens and physical performance. - M., 1997. - 267 C.]. The rats of the experimental group was administered intragastrically broth Adaptivity in a volume of 10 ml/kg within 7 days prior to stress exposure (1 time a day for 30 minutes before feeding). Animals of control group received equiano amount of distilled water on a similar scheme. As the comparison drug used dealcoholizing extract of Eleutherococcus in an amount of 5 ml/kg After 7 days from the beginning of the insertion was determined by the overall physical endurance by swimming animals to exhaustion, a criterion which served as the first dive of the animal under water for 10 seconds, and then under light ether anesthesia, rats were deceptional and determined in the homogenates of skeletal muscle ATP content [Aleinikov T.A., Rubtsova GV Quantitative determination of high energy compounds muscles (ATP, creatine phosphate) // a Guide to practical is their practice of biological chemistry. - M., 1988. - S-117], breast (MK) and pyruvic acid (PVA) [Kolb VG, Kamyshnikov B.C. Handbook of clinical chemistry. - Minsk, 1980. - 231 S.], glucose, total protein, triacylglycerides (TG), cholesterol (LDL), high density lipoprotein (HDL), lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) in serum. The study was conducted on the analyzer SAP-PHIRE 400 (Japan). The content of glycogen in the liver homogenate was determined by the method of S. Seifter [Seifter, S., et al. The estimation of Glycogen with the Antron Reagent // Arch. Biochem. - 1950. - Vol.25. - P.191-200]. The obtained data are presented in tables 3-4. Intense exercise is accompanied by a decrease in the concentration of ATP in skeletal and cardiac muscles. In addition, in the face of intense physical activity observed depletion of carbohydrate reserves, namely the decrease in the concentration of glycogen in the liver (Table. 3).
|The influence of Adaptivity on General physical endurance and indicators of energy status of the organism of white rats on the face of physical activity|
|Index||The intact group||The control group||Experienced the group|
|ATP, umol /g||2,55±0,030||0,76±0,03||2,04±0,06*||1,80±0,06*|
|TG, mmol/l||0,80±0,067||1,04±0,085||0,81±to 0.127||0,90±0,124|
|Note: * the differences are significant compared to control at P≤0,05|
Preventive repeated introduction of Adaptivity caused pronounced act-protective action, as evidenced by the increase of the overall physical health of the animals from the experimental group: the length of the voyage has increased 2.7 times compared with animals of the control group, a study of indicators of energy metabolism suggests that increasing physical endurance of animals under the influence of the tool caused by the activation of the resin is ESA ATP: its content in skeletal muscle was 2.4 times higher compared to the same indices of animals in the control group. In addition, the introduction of Adaptivity was accompanied by an increase in carbohydrate reserves in the liver: the concentration of glycogen in the liver of animals from the experimental group was higher, and, consequently, increase the concentration of glucose in serum by 47% compared with the control group. Marked decrease in the activity of such enzymes LDH and CPK in animals treated with the test tool, 25 and 29%, respectively (Table. 3).
Thus, the obtained data indicate that Adaptivit has a pronounced adaptogenic activity, raising nonspecific resistance of animals in intensive exercise.
2. The study of anti-stress activity of Adaptivity.
The experiments were carried out on white Wistar rats of both sexes weighing 180-220 g Immobilization stress reproduced the conventional method by fixing the animal in position on the back for 18 h [A. Yumatov E.A., Schieles YG Comparative analysis of the sustainability of the functions of the cardiovascular system in rats of different lines when immobilization // Ukr. higher nerve. activities. - 1979. No. 2. - S-350]. The rats of the experimental group was administered intragastrically the broth Adaptivit in a volume of 1.0 ml/100 g for 7 days prior to stress exposure (1 time a day for 30 minutes before feeding). Animals of control group received equiano amount of distilled water similar is offered by the scheme. As drug comparison, another group of animals was injected dealcoholizing extract of Eleutherococcus in an amount of 5 ml/kg On day 7 of the experiment, animals from the control and experimental groups were subjected to immobilization stress, after which the animals were deceptional under light ether anesthesia and determined the severity of the triad Selye: the hypertrophy of the adrenal glands, the state of immunocompetent organs and the emergence of destructive lesions in the gastric mucosa count "ulcer index" Pauls [Obolentseva, GV, Haji YA, Widuchowa A.I., Laganovska YU.V. Influence of certain natural substances in ulcerative damage to the stomach of rats caused by acetylsalicylic acid // bull. the experts. biology and medicine. - 1984. No. 3. - P.39-40]. The obtained data are given in table 4-5.
|The influence of Adaptivity on the weight of the thymus, spleen and adrenal glands of Wistar rats during immobilization stress|
|Groups of animals||The mass of bodies, mg/100 g|
|the thymus||spleen||the adrenal glands|
|The intact||to 123.5±4,50||521,0±16,45||21,0±1,54|
|Stress+Adaptivit||105,6±3,59*||332,5±grade of 20.06*||26,7±1,5*|
|Stress+Siberian ginseng||to 108.2±1,97*||308,30±3,82*||28,3±0,77*|
As follows from the data shown in table 4, the experimental animals, a decrease of adrenal masses by 26% compared with rats of the control group and course introduction Adaptivity at a dose of 100 mg/kg of the stress increases the weight of immune organs: thymus - 45%, and spleen by 60%.
Along with this introduction to the animals of the test tools had expressed gastroprotective action, delaying the development of deep destruction of the gastric mucosa of Wistar rats (table 5). Thus, in the experimental animals the number of petechial hemorrhages and erosions were found in 25% of cases with lesions in control at 66%. Accordingly, the index Pauls for dot haemorrhages in animals treated with the test agent, who was b less than that of the rats of the control group and was 0,125 0,4, and for ulcers - 0,125 against 0.400 in control. However, rats receiving Adoptapet, was not observed the formation of erosions, whereas the animals of the control group and 66% of the cases noted the appearance of such mucous (PL. 5).
|The influence of Adaptivity on the severity of damage of the gastric mucosa in white rats on the background of the 18-hour immobilization stress|
|Index||The intact group - e group||The control group (stress+H2O)||Experienced group|
|Hemorrhage||% of affected animals||0||66||25||0|
|The average number of destruction 1 animal||0||0,6||0,5||0|
|Erosion||% of affected animals||0||66||0||33*|
|The average number of destruction 1 animal||0||1,33||0||1|
|Ulcers||% of affected animals||0||66||25||0|
|The average number of destruction 1 animal||0||0,6||0,5||0|
In the group of animals treated with the extract of Siberian ginseng, de is reconstructive lesions of the gastric mucosa was observed only erosion in 33% of cases. The mucosa of the stomach of rats included in the control group, was observed pronounced edema and hyperemia, whereas in rats treated subjects means, swelling and smoothness of the terrain of the gastric mucosa were moderate.
The findings suggest that Adaptivit has anti-stress activity, preventing the development of catabolic changes due to immobilization and painful stress.
3. The study of hepatoprotective activity of Adaptivity when tetrachlorocarbon hepatitis.
Acute toxic hepatitis reproduced by subcutaneous injection of 50% oil solution of carbon tetrachloride (STT) in a volume of 0.4 ml/100 g of animal 1 time a day for 4 days [Manual on experimental (preclinical) study of new pharmacological substances. - M - 2000. - S-232]. Animals of the 1st experimental group intragastric introduced broth Adaptivity for 21 days in a volume of 5.0 ml/kg body weight of 1 times a day 30 minutes before a meal. As of Comparators: 2 nd experimental group of rats was administered Califon in isoeffective a dose of 100 mg/kg weight of the animal and the 3rd experimental group of animals on a similar scheme was introduced the product comparison - dealcoholizing solution Eleutherococcus in an amount of 5 ml/kg according to the same scheme. Animals of the control group was administered intragastrically on a similar scheme distiller annoy water.
To evaluate the hepatoprotective activity Adaptivit determined biochemical parameters characterizing the functional state of the liver of laboratory animals: the activity of alanine aminotransferase (ALT), aspartate aminotransferase (ACT), the content of total bilirubin and alkaline phosphatase activity (alkaline phosphatase) in serum were determined by standard methods [Laboratory methods in the clinic: a Handbook. Under. edit Riv. - M.: Medicine, 1987. - 368 S.]; excretory-absorbing function of the liver was estimated by the rate of excretion of bromsulphalein with bile [Solov'ev V.I., Egorenko GG, Firsov A.A. the Use of a mathematical model of pharmacokinetics in the study of the liver in albino rats by the method of bromsulphalein samples // Laboratory work. - 1976. No. 9. - S-542]. Antipyrine was administered to rats intraperitoneally at a dose of 50 mg/kg, determination of antipyrine in serum was performed after 1, 2, 3 and 4 hours. To assess the impact of tools on the processes of synthesis in the body in the liver tissue homogenates was determined by the content of glycogen. The data are processed statistically using U-test, Mann-Whitney [Sergienko V.I., Bondareva IB Mathematical statistics in clinical research. - M - 2000. - 263 S.].
Obtained in experiments data indicate that liver damage in rats chetyrekh stem carbon accompanied by the development of cytolysis syndrome (PL. 6). Under the influence of the specified hepatotropic poison marked increase in the activity of membrane-bound enzymes in the blood serum of Wistar rats: Alt activity to 7 days study increases by 32%, AST - 24% compared with those in intact rats (Table 6). In exchange introduction Adaptivit volume of 5.0 ml/kg on the background of toxic hepatitis activity of these enzymes is reduced in comparison with the control, respectively at 32 and 29%. While these indicators when using drugs comparison Siberian ginseng and kalapana declined: AcT 20 and 24%, Alt - on 20 and 28%. In the study at 14 and 21 days of experiment transaminases in rats of the test group receiving Adoptapet, was also significantly lower than in animals of the control group.
It was also established that intoxication tetrachlorethane accompanied by the development of cholestatic syndrome. In particular, on day 7 in animals of the control group in serum alkaline phosphatase activity increased by 42%, and the content of total bilirubin 2.6 times compared with those in intact rats. In exchange introduction of the test tools alkaline phosphatase activity and the content of bilirubin in the serum was decreased on average by 30 and 22%, respectively, compared to rates in the control (Table. 6).
|The influence of Adaptivity on biochemical parameters of blood serum of Wistar rats with liver damage by carbon tetrachloride|
|Indicators||Groups of animals|
|The intact||Control||Experienced (CCL4+)|
|Alkaline phosphatase, a unit Baud.||14,0±1,28||24,0±1,30||20,0±2,10*||18,0±3,9*||17,0±3,0*|
|The total bilirubin mg%||5,0±0,45||14,0±0,13||13,0±1,5*||12,4±2,4||11,0±2,10*|
|MDA in the liver homogenate, nmol/g||0,30±0,02||1,00±0,05||0,60±0,05*||0,50±0,04 *||0,40±0,02*|
|MDA in the serum. Μmol/ml||2,10±0,15||5,80±0,35||4,00±0,37*||3,00±0,14 *||2,50±0,10*|
|Katal Aza, mkat/l||1,40±0,11||1,00±0,25||1,30±0,15||2,3±0,25*||3,00±1,15*|
|Alkaline phosphatase, a unit Baud.||14,0±1,00||27,3±1,0||20,1±5,10*||17,0±1,12*||15,0±1,11*|
|The total bilirubin, mg%||0,5±0,03||4,6±0,15||2,90±2,10*||2,6±0,13*||1,5±0,10*|
|Alkaline phosphatase, a unit Baud.||13,0±1,5||22,6±2,4||16,0±2,5*||14,5±2,5||13,0±1,8|
|The total bilirubin, mg%||0,5±0,03||1,9±0,09||1,5±2,8*||1,5±0,05*||1,0±1,9*|
When using drugs comparison Siberian ginseng and kalapana alkaline phosphatase decreased by 17% and 25%, respectively, and the content of bilirubin by 8 and 12%, respectively. The same trend has continued in subsequent follow-up period (14 and 21 days). Thus Adaptivit on pharmacotherapeutic efficacy superior to Comparators (Eleutherococcus, Califon).
It is established that the course introduction of Adaptivity rats with toxic hepatitis is accompanied by a decrease in the intensity of peroxidation processes. Thus, the concentration of MDA in serum and liver homogenate of animals of this group on the 7th day decreases respectively 57% and 60% compared with the same indicators in rats of the control group. Simultaneously, under the influence of the test tools has increased the capacity of the antioxidant system of the organism: the activity of cat is manholes increases in 3 times, and the content of sulfhydryl groups in blood serum is increased by 20% compared with those of the rats of the control group. According to its pharmacological effectiveness Adaptivit exceeds the Comparators (Eleutherococcus, Califon).
The introduction of carbon tetrachloride white rats is accompanied by a pronounced violation of excretory-secretory function of the liver, as indicated by the delay of elimination of xenobiotics from the body (PL. 7).
|The influence of Adaptivity on the antitoxic function of the liver in rats in acute toxic hepatitis (7 day)|
|Groups of animals||The half-life of antipyrine, %||The half BSF, %|
|Experimental 1 (CCl4Siberian ginseng)||118||136|
|Experienced 2 (CCl4+Califon)||112||121|
|Experienced 3 (CCl4+Adaptivit)||108||114|
Adaptivit shows antitoxic activity by liver damage by carbon tetrachloride (PL. 7). Thus, the rate of excretion of bromsulphalein (BSF) and antipyrine with bile in animals treated with hepatotropic poison, is sharply reduced, the period of their half-life at 45% and 28%, respectively, higher than the indices in intact rats. On the background of a course of introduction of the test means the rate of elimination of BSF and antipyrine with bile increases on 22 (31) % and 16 (20) % compared with rats in the control group, and the Comparators Eleutherococcus by 10 and 9%, respectively, of kalapana by 16% and 24% respectively. The findings suggest that the activation of the excretory functions of the liver under the influence of the test means, and Adoptapet on antitoxic activity superior to that of Comparators.
Thus, the study has found that Adaptivit in exchange introduction of a volume of 5.0 ml/kg has a pronounced hepatoprotective activity, not inferior to any of the Comparators (Eleutherococcus and kalapana).
In General, these studies indicate pronounced adaptogenic activity ADAP is the ophiolite in conditions of intense physical exertion, impact of stress factors and the actions of xenobiotics (carbon tetrachloride), surpassing in some criteria Comparators (extract of Siberian ginseng, Califon).
4. The study of the immunomodulatory activity of Adaptivity.
Experiments conducted on mice-males line F1(CBA×C57B1/6) weighing 18-20, the Action of the investigated tools on indicators of cellular, humoral and macrophage immunity was studied in intact animals and animals in a state of immunosuppression caused by cytostatic azathioprine, which was administered to animals at a dose of 50 mg/kg orally 1 time a day for 5 days [Genesareth, Equilenin. Immune stimulants. - M., 1985. - 256 S.]. Adaptivit have introduced the 1st experimental group on the background of azathioprine and 2nd experimental group intact mice in a volume of 10 ml/kg orally 1 time a day for 14 days. The intact and control group animals received water purified according to the same scheme. As the comparison drug used liquid extract of Eleutherococcus senticosus (EEC) in an amount of 5 ml/kg orally 1 time a day for 14 days.
The effect of the test tool on the state of the cellular immune response was evaluated in the reaction of hypersensitivity of the delayed type (GST) according to the standard technique of local GST. Mice were senzibilizirani vnutribruchinnogo a 0.1%suspension of sheep erythrocytes (EB) in physiological solution. On the 4th day under the plantar aponeurosis of the hind paws was introduced allowing the antigen dose of 50 ál of a 50%suspension of DL. In the contralateral paw was injected with saline in the same volume. The estimation of the reaction GST was performed after 24 hours according to the difference of mass experienced (Ro) and control (RK) feet.
The state of the macrophage level of immune response was evaluated in the reaction of phagocytosis of peritoneal macrophages in respect of the colloidal particles of the carcass. The optical density of the lysate of the cells of peritoneal exudate, reflecting the number of carcasses deposited by peritoneal macrophages was determined at a wavelength of 620 nm [Manual on experimental (preclinical) study of new pharmacological substances, Ed. Rugarama. - M., 2005. - S]. The state of humoral immunity was assessed by the number of antibody productive cells (AFC), determined by the method of local hemolysis on A.J.Cunningham [Cunningham A.J. And method of increased sensitivity for detecting single antibodyforming cells // Nature. - 1965. - Vol.207, No. 5001. - P.1106-1107]. Mice were immunized intraperitoneally EB dose of 2*108cells in the mouse. The reaction was set at 5 days after immunization. The obtained results were processed by the statistical method using student's criterion.
When studying the effect of Adaptivity on the processes of the antibody productions found that this tool restores indicators GU the oral immune response in terms azathioprine immunosuppression. The introduction of azathioprine resulted in a decrease of the absolute number of the KLA, and the number of KLA 106 splenocytes by 45% and 37%, respectively, compared to the same indicators in the intact group (table 8).
|The influence of Adaptivity on the antibody production|
|Groups of animals||The absolute number of AFC in the spleen||The number AOK 106the splenocytes|
|1 experienced (azathioprine+Adaptivit)||77663±4286*||319±21*|
|2 experienced (Adaptivit)||59614±3678||322±27|
|3 experienced (azathioprine+AAC)||62571±4364*||297±23*|
With the introduction of an investigational tool on the background of immunosuppression observed a significant increase in the number of KLA both in absolute values and PR is based on the 10 6the splenocytes; the first figure was higher than the level azathioprine suppression 2.7 times, and the second - 1.6. The product comparison - EACH increased absolute and relative number of KLA 2.2 and 1.5 times, respectively.
With the introduction of Adaptivity intact animals found that this tool does not have a significant effect on the indices of humoral immunity in intact animals.
When studying the effect of Adaptivity on cell-mediated reaction GST found that the test tool restores the index of this reaction (IL GST) in azathioprine immunosuppression. The introduction of azathioprine resulted in reduced IL GST by 44% compared with the same indicator in the intact group (table).
|The influence of Adaptivity on the severity of hypersensitivity reactions of the delayed type (GST)|
|Groups of animals||IL GST, %|
|Control (azathioprine), n=10||19, 22 the±1,76|
|1 experienced (azathioprine+Adaptivit), n=10||44,19±3,2*|
|2 experienced (Adaptivit), n=10||37,46±2,54|
|3 experienced (azathioprine+AAC), n=10||29,12±1,86*|
With the introduction of the test tool on the background of immunosuppression observed an increase in IL GST 2.3 times compared with the control, whereas EACH increased the index of the reaction GST only 1.5 times. In the intact animals using Adaptivity not noted significant changes in this indicator compared to the intact group (Table. 9).
In the study of the influence of Adaptivit on phagocytic activity of peritoneal macrophages intact mice against particles of colloidal carcass found that this tool does not modify the phagocytic index compared to the intact group (Table. 10).
|The influence of Adaptivit on phagocytic activity of peritoneal macrophages|
|Groups of animals||Phagocytic index, Optical density, usled|
|1 experienced (azathioprine+Adaptivit)||0,028±0,0028*|
|2 experienced (Adaptivit)||0,030±0,0024|
|3 experienced (azathioprine+AAC)||0,019±0,0016*|
With the introduction of this tool, animals with human immunodeficiency observed an increase in the phagocytic index of 2.2 times compared with those in the control group, and the use of AAC has led to an increase in phagocytic index in 1,5 times in comparison with the control (table 8).
Thus, Adaptivit able to reduce the suppressive effect of azathioprine on the indicators of cellular, humoral and macrophage parts of the immune response. The monitoring tool does not change the performance of the immune system intact animals. This property is inherent only true immunomodulators, with activity only in terms of damage to the immune system.
The above experimental data indicate that Adaptivit has a pronounced adaptogenic activity and exerts immunomodulatory effects in conditions of immunosuppression.
The tool that has adaptogenic and immunomodulatory activity, containing vegetable raw materials - florets of calendula, roots and rhizomes of Rhaponticum carthamoides, elecampane is high, calamus swamp, ginger, fruits, nutmeg, cardamom, characterized in that the quality of plant raw material additionally contains the roots of the marshmallow pharmacy, grass knotweed, the bark of the cinnamon tree, the pomegranate fruit, long pepper, juniper, leaves black bergenia tolstolistnogo and chitosan, parts: florets of calendula - 13,0; roots and rhizomes of Rhaponticum carthamoides - 13,0; roots of elecampane - 7,0; the fruit of the nutmeg - 5,0; cardamom fruit - 9,0; the roots of calamus swamp - 5,0; the roots of Althea pharmacy - 5,0; rhizomes of ginger - 4,5; herb Polygonum bird - 5,0; the bark of the cinnamon tree is 4.5; the pomegranates - 11,5; peppers long - 6,5; the fruit of the juniper - 5,0; leaves black bergenia tolstolistnogo - 3,0; chitosan to 3.0.
SUBSTANCE: group of inventions relates to medicine, in particular to gastroenterology, and deal with treatment of ulcerative colitis and Crohn's disease. Method of treatment includes introduction into organism of therapeutically efficient quantity of attaching cells from placenta, cultivated in such a way as not to differentiate into adipocytes or osteocytes. Also claimed is application of said cells for obtaining medication, intended for treatment of ulcerative colitis or Crohn's disease. Claimed produced product for treatment of ulcerative colitis or Crohn's disease includes in packing form pharmaceutically efficient quantity of said cells.
EFFECT: inventions ensure essential reduction of inflammatory process in colon in modelling of said diseases, as well as due to pathological mechanisms of treatment in addition to T-lymphocyte suppression.
31 cl, 5 ex, 12 tbl, 16 dwg
SUBSTANCE: invention refers to medicine, particularly to paediatrics and neonatology, and can be used for treating small premature infants at the hospital stage of developmental care. A therapeutic complex comprises administering a probiotic preparation into the newborns. The preparation is presented with a liquid probiotic containing E.faecium L3 109 CFU in 1 ml. If the enteral nutrition volume of the newborn is 5 ml or more, this preparation is orally administered in a dose of 0.5 ml 3 times a day for 14 days.
EFFECT: method is effective in children with a very low body weight, promotes normalising the intestinal microflora and reducing a rate of manifestations of infectious complications.
2 ex, 3 dwg, 3 tbl
SUBSTANCE: group of inventions relates to biotechnology and medicine. Disclosed is a polysaccharide which is isolated from the Bifidobacterium infantis NCIMB 41003 strain and has the structure [-β(1,3)-D-GalpNAc-β(1,4)-D-Glcp-]n, where said disaccharide unit repeats n times, which yields a polysaccharide with molecular weight greater than 100000 Da. The polysaccharide exhibits immunomodulating activity and is used in preparing medicinal agents for treating or preventing undesirable inflammatory activity, undesirable gastrointestinal inflammatory activity, rheumatoid arthritis and autoimmune disorders.
EFFECT: pharmaceutical composition for treating and preventing inflammatory disorders and a food product containing the isolated polysaccharide are disclosed.
9 cl, 6 dwg, 3 ex
SUBSTANCE: invention relates to a compound CL168 of general structural formula I where R is oxygen. The invention also relates to a method of producing a compound of formula I and use of the compound of formula I to produce a medicinal agent for preventing or treating tumorous and immunological diseases.
EFFECT: compound of formula I for producing a medicinal agent for preventing or treating tumorous and immunological diseases.
4 cl, 11 tbl, 19 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutical industry, namely to an immunomodulator. An immunomodulator for the immunocorrection accompanying the integrated treatment of chronic non-specific pulmonary diseases, chronic obstructive pulmonary disease, bronchial obstruction syndrome, chronic bronchial pneumonia, pulmonary fibrosis, tracheobronchitis, chronic laryngitis, pulmonary, tracheal and pharyngeal cancer; the immunomodulator is prepared by mixing a water infusion of rose bay leaves and a water infusion of yellow melilot taken in equal proportions, with a cattle lung and larynx powder, settling the prepared mixture, keeping on a boiling water bath, cooling; further, the mixture is filtered; the prepared solution is added with cattle blood serum containing leukaemia oncovirus antibodies, hemlock infusion, ascorbic and sorbic acids until all the ingredients fully dissolved; the prepared solution is placed in the water bath, cooled, filtered, sterilised under certain conditions.
EFFECT: above preparation provides higher effectiveness and reduces the length of treating the above diseases, and ensures the higher immunobiological properties of the human body.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutical industry, namely to an extract of one or more bacterial strains Lactobacillus. The extract of one or more bacterial strains Lactobacillus representing a soluble extract, wherein the extract contains chemically modified bacterial molecules prepared by the action of an alkaline medium on one or more bacterial strains Lactobacillus; the extract is effective in treating diseases associated with the anti-inflammatory cytokine production imbalance. A method for preparing the extract of one or more bacterial strains Lactobacillus. A pharmaceutical composition effective for reducing at least one symptom associated with at least one condition specified in a respiratory disorder, an allergic condition, an urinary disorder and a gastric disorder, containing the extract. A nutritional composition. A pharmacological composition effective in treating the diseases associated with the anti-inflammatory cytokine production imbalance, containing the extract. A method of relieving the above symptoms. The extract prepared by the above method.
EFFECT: extract is effective in treating the diseases associated with the anti-inflammatory cytokine production imbalance.
21 cl, 7 dwg, 23 tbl, 5 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions refers to medicine, namely to using at least one immunomodulatory compound of general formula (1) or a pharmaceutically acceptable, solvate or isomer thereof for preparing a pharmaceutical composition for treating a disease or disorder specified in asthma, atopic dermatitis, allergic rhinitis, inflammatory intestinal disease, diabetes or rheumatoid arthritis in homoiothermal animal, including a human. What is also presented is using (5S,11R)-1-amino-5-[(R)-3-dodecanoyloxytetradecanoylamino]-6-oxo-7-aza-11-[(R)-3-hydroxytetradecanoylamino]dodecan-12-ol-12-dihydrophosphate (OM-294-BA-MP (S,R)) or a pharmaceutically acceptable salt, solvate or isomer thereof for preparing the pharmaceutical composition.
EFFECT: group of inventions provides treating the above diseases by modulating the TH1/TH2 cytokine balance by reducing TH2-cytokine release and enhancing TH2-cytokine production.
11 cl, 16 dwg, 14 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to biotechnology, more specifically to preparing interferonogenic antiviral agents of yeast RNA, and may be used in medicine. The IFN-γ inducer is presented by a soapy amphiphilic complex of high-polymer Saccharorayces cerevisiae RNA and oleic acid penetrating easily through biological membranes in the following proportions: high-polymer RNA - 80-90%, oleic acid - 10-20%.
EFFECT: invention enables inducing interferon γ (IFN-γ) production effectively with using available and low-cost ingredients.
2 tbl, 5 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutical industry, namely a method for preparing an agent possessing immunomodulatory activity. The method for preparing an agent possessing immunomodulatory activity characterized by the fact that herbal composition containing common motherwort herb, knotgrass herb, pot marigold blossom, licorice rhizome and root, Alexandrian laurel rhizome and root, rosehip, schizandra fruit, linseeds, sequentially twice extracted in 60-70% ethanol, twice in 40-50% ethanol, and once in purified water under specific conditions; then the aqueous-alcoholic extracts are concentrated in vacuum; the aqueous still residues are combined with the aqueous extract, then filtered, boiled out, purified by separation, boiled out additionally, dried in a vacuum dryer and further milled.
EFFECT: method enables preparing the agent possessing manifested immunomodulatory activity with the high content of active substances.
13 tbl, 2 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pyridine derivatives of formula (I) wherein A, R1, R2, R3, R4, R5, R6 and R7 are presented in the description, preparing and using them as pharmaceutically active compounds possessing SP1/EDG1 receptor agonist activity.
EFFECT: using the declared compounds or pharmaceutically acceptable salts thereof for preparing a pharmaceutical composition for preventing or treating the diseases or disorders associated with the activated immune system.
13 cl, 76 ex, 2 tbl
SUBSTANCE: invention relates to water-dispersible polyurethane, method of obtaining thereof, thereof application and cosmetic preparation, containing polyurethane as thickening agent. Water-dispersible polyurethane contains mainly linear basic chains, consisting of alternating hydrophilic and hydrophobic sections. Polyurethane has two terminal sections (T), which are hydrophobic, and, at least, one hydrophobic terminal section (T) represents branched alkyl residue. Hydrophilic section (S) is directly attached to each section (T). At least, one hydrophobic section (D) is directly attached to, at least, one end of each of sections (S). The main polyurethane chain contains, at least, one hydrophilic section (P), and if there is more than one section (P), two sections (P) are separated with, at least, one hydrophobic section (D). Polyurethane contains, at least, three hydrophilic sections. Ratio of molecular weight of any of hydrophilic sections (S) to molecular weight of any of hydrophilic sections (P) lies within the interval from 1:1.4 to 1:70. At least, two hydrophobic sections (D) are aliphatic diisocyanate residues, and, at least, one hydrophilic section (P) represents residue of polyether with number average molecular weight, at least, 1500 g/mol. Polyurethane can represent mixture of different mentioned above polyurethanes. Polyurethanes are obtained in two steps. At the first stage interaction of, at least, one polyether diol with, at least, one aliphatic diisocyanate is realised in presence of zinc carboxylate in solvent medium. At the second stage obtained product is subjected to interaction with, at least, one ethoxylated aliphatic alcohol in solvent medium. After that, separation of solvents is performed and water is added. Polyurethanes are applied for manufacturing of water-containing cosmetic preparation.
EFFECT: invention makes it possible to increase viscosity of cosmetic preparations and their storage stability.
10 cl, 4 tbl, 11 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to versions of medication for reduction of halitosis, versions of compositions based on said medications and versions of application of said medications. Device for reduction of halitosis represents strains of microorganisms Lactobacillus acidophilus, selected from group Lactobacillus acidophilus DSM 19825, Lactobacillus acidophilus DSM 19826 and Lactobacillus acidophilus DSM 19827. Version of said medication represents culture supernatant of said strains. Also claimed are compositions, which contain said microorganisms, and their application for reduction of halitosis.
EFFECT: invention makes it possible to considerably reduce concentration of peptides in saliva, depleting in this way substrate, used by anaerobic microorganisms of oral cavity microflora, which are halitosis-causing agents.
10 cl, 7 dwg, 19 ex
SUBSTANCE: invention relates to a method of removing pesticides from Ginkgo biloba extracts. The method involves subjecting an extracted obtained by extracting Ginkgo biloba leaves with hexane, comprising the following steps: a) liquid-liquid extraction to obtain a medium polarity fraction containing ginkgo terpenes and pesticides not removable with hexane, and a high polarity fraction containing ginkgo flavone glycosides; b) crystallisation from the medium polarity fraction obtained at step a) to form an intermediate with ginkgolide content of not less than 50%; c) crystallisation from the residual solution obtained at step b) to obtain an intermediate product with bilobalide content of not less than 50%; d) mixing of the high polarity fraction obtained at step a) with the ginkgo terpene intermediate product and the bilobalide intermediate product obtained at steps b) and c).
EFFECT: invention enables to obtain a product with a given ratio of terpenes, in which residual content of pesticides is considerably low or pesticides are completely removed.
4 cl, 1 tbl, 5 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to pharmaceutical industry, namely to homeopathic suppositories for treatment of fungal colpitis, vulvovaginitis, endometriosis, papillomas, cervical erosion, candidosis and vaginal dryness (versions). Homeopathic suppositories for treatment of fungal colpitis, vulvovaginitis, endometriosis, papillomas, cervical erosion, candidosis and vaginal dryness, contain Sea buckthorn oil, homeopathic oil extract, thuya oil, melaleuca oil, juniper oil, homeopathic essence of eucalyptus, homeopathic essence of elder flower, homeopathic essence of wormwood, thick extract of galium, thick extract of cimicifuga, base, taken in specified quantity. Homeopathic suppositories for treatment of fungal colpitis, vulvovaginitis, endometriosis, papillomas, cervical erosion, candidosis and vaginal dryness, containing Sea buckthorn oil, homeopathic oil extract, valerian oil, Melissa oil, Humulus lupulus oil, homeopathic essence of Viscum album, homeopathic essence of jaborandi, thick extract of galium, thick extract of cimicifuga, base, taken in specifies quantity. Homeopathic suppositories for treatment of fungal colpitis, vulvovaginitis, endometriosis, papillomas, cervical erosion, candidosis and vaginal dryness, containing homeopathic oil extract, beggar-ticks oil, homeopathic essence of lycopodium, homeopathic essence of cantharis, thick extract of galium, thick extract of cimicifuga, base, taken in specified quantity.
EFFECT: suppositories are efficient for treatment of fungal colpitis, vulvovaginitis, endometriosis, papillomas, cervical erosion, candidosis and vaginal dryness.
3 cl, 5 ex
SUBSTANCE: invention represents a pharmaceutical composition for treating local manifestations of herpes simplex infections and for preventing influenza and acute respiratory viral infections, containing green tea extract and epigallocatechin-3-gallate (EGCG) 70-90 wt %, colloidal silver and a gel-forming base with the ingredients of the composition taken in certain ratio, wt %.
EFFECT: high clinical effectiveness.
6 cl, 8 ex, 5 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to pharmaceutical industry, namely to enterosorbent and method of its obtaining. Enterosorbent based on peat, free from lipids, additionally contains cranberry cake, prebiotic with specified component ratio. Method of obtaining enterosorbent from preliminarily dried sphagnum peat includes extraction of lipids with solvents, mixing with cranberry cake, crushing, mixing with solution of prebiotics - lactulose or lactose and drying.
EFFECT: method makes it possible to extend assortment of natural enterosorbents with improved properties: high enterosorbing capability and prebiotic activity.
2 cl, 1 tbl, 2 ex
SUBSTANCE: invention relates to cosmetology, detergent compositions and discloses a universal dry agent in form of a powder containing ground parts of saponin-containing plants which release surfactants immediately upon activation, and specifically parts of a soap root or a soap tree in amount of 5-99.9 wt %. Natural auxiliary components which perform stabilising and anti-caking functions in the detergent are zeolite, ground mustard, salt, guar or quartz in amount of 0.1-95 wt %. The powder has particle size of 0.005-2000 mcm.
EFFECT: detergent is save for use, has a long shelf life, does not cake and is characterised by simple use of saponin-containing plants as a detergent base.
1 tbl, 1 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutical industry, specifically to a drug preparation possessing adaptogenic activity. Ginseng syrup possessing adaptogenic activity containing 40% alcoholic tincture of ginseng roots, sorbitol or fructose and purified water in certain proportions.
EFFECT: preparing the agent possessing adaptogenic activity.
3 dwg, 2 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to cosmetology and represents a complex cosmetic agent containing hyaluronic acid, colloidal silver, emulsion wax, water, carnosine, enfolin recovered from hydrogel of hyaluronic acid in the process of photochemical nanostructuring at wave length equal to 280 nm, while hyaluronic acid is nanostructured at a diameter of single chains up to 5 nm with the ingredients of the agent taken in certain ratio, wt %.
EFFECT: invention provides rejuvenating effect, anti-inflammatory action and lifting effect, besides it possess local immunostimulative action, extended storage period and high biological activity.
1 tbl, 3 dwg
SUBSTANCE: drug preparation represents a composition containing: lappaconitine hydrobromide 0.02 - 0.06 g, pregelatinised starch 0.0335 - 0.0536 g, lactose monohydrate 0.058 - 0.122 g, hypromellose 0.078 - 0.161 g, calcium stearate 0.002 - 0.004 g and colloidal silicone dioxide 0.002 - 0.004 g.
EFFECT: prolonged antiarrhythmic action of the active ingredient lappaconitine hydrobromide with accessory alkaloids.
5 cl, 1 tbl
FIELD: medicine, oncology, amino acids.
SUBSTANCE: invention relates, in particular, to the development of an antitumor preparation based on natural substances. Invention relates to an amino acid preparation comprising at least one modified essential amino acid obtained by treatment of amino acid by ultraviolet radiation (UV) at wavelength 250-350 nm for 12-80 h at temperature 15-30oC or with ozone at temperature 15-25oC. The modified amino acid has no toxicity for health cells. Also, invention relates to a method for preparing such preparation. Invention provides the development of an antitumor preparation based on modified amino acids and expanded assortment of antitumor preparations being without cytotoxicity for normal cells.
EFFECT: valuable medicinal antitumor properties of preparation.
8 cl, 4 tbl, 2 dwg, 4 ex