Agent having adaptogenic activity. RU patent 2506090.

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, namely an agent possessing adaptogenic activity. An agent possessing adaptogenic activity, containing ground spiny eleuterococcus roots, snowdone rose roots, Ural licorice roots, bilberry shoots, creeping thyme herb in the certain environment.

EFFECT: agent possesses the manifested adaptogenic activity.

6 tbl, 3 ex

The invention relates to medicine, in particular to pharmacology and affects tools from plant collection, which has activity.

Known adaptogen plant and animal origin (liqueur of schisandra fruit, , aralia, ginseng root extract levzei, Rhodiola rosea, Eleutherococcus, Pantocrinum, , and others) have the ability to enter the body in a state of nespecificski high resistance by regulating the flow of stress reactions, improve resistance of cells and organisms in the damaging action of harmful factors (... Teaching N.V. Lazarev, CNPC and as basic theory of preventive medicine. // Psychopharmacology and biological narcology. 2005. V.5. №4. .1086-1092). Despite the growing Arsenal of new adaptogens, development and introduction of new activity of a widespread and availability of raw materials is an important challenge in practical pharmacy.

The technical result to be obtained by carrying out the invention, is the expansion of a range of highly effective and harmless medicines for raising resistance of an organism during increased physical and mental stress.

Result is achieved by means of possessing activity, is characterized by the fact that it contains the roots of Eleutherococcus senticosus, the roots of Rhodiola rosea, Ural licorice roots, shoots bilberry, grass creeping thyme in the following ratio, mass%:

the roots of Eleutherococcus senticosus - 18-22,

the roots of Rhodiola rosea 13-17,

the roots of Ural licorice 18-22,

shoots bilberry 18-22,

grass creeping thyme 23-27.

For the proof of the essentiality of the suggested characteristics of the method, namely the ratio of raw materials, conducted a series of experiments, data are presented below.

The experiments used raw materials, the quality of which corresponds to the existing articles of the GF XI ed. (State Pharmacopoeia of the USSR: Issue 1. General methods of analysis. USSR MINISTRY OF HEALTH. - 11-e Izd., extra - M: Medicine. - 1987. - 337 C.; V.2. General methods of analysis. Medicinal plant raw materials. USSR MINISTRY OF HEALTH. - 11-e Izd., extra - M: Medicine. - 1990. - 400 C) and the relevant state standards (GOST 29046-91). Raw material crushed separately, according to the requirements of the respective standards and GF X ed. (State Pharmacopoeia of the USSR. X ed. - M, 1968. Article 349 «Infusions and decoctions». .370-372): - particle size of 0.5-2.0 mm Improvement of the technology of preparation and quality control of vitamin teas. / Actual problems of pharmaceutical technology: Scientific. proceedings of the collection of vniif articles. - .32. - M, 1997. - P.151-159).

Example 1. Crushed to a particle size of 0.5-2.0 mm and sifted: the roots of Eleutherococcus senticosus (Eleutherococcus extract senticosus (Rupr. et Maxim.) - 18 - 22%, the roots of Rhodiola rosea (Rhodiola rosea L.) - 13-17%, the roots of Ural licorice (Glycyrrhiza uralensa Fisch.) - 18-22%, shoots of bilberry (Vaccmium myrtillus L.) - 18-22%, grass creeping thyme (Thymus serpyllum L.) - 23-27% mixed.

To assess activity of the means test examined the impact of the means test on the overall physical, power, speed endurance test animals on the different models. Before the experiments, to eliminate the influence of ethyl alcohol, drug comparison - liquid extract of Siberian ginseng (VFS 42-1281-82) rotary evaporator at 37 C up to 1/10 of original volume, the aqueous balance brought distilled water to the original volume.

The specified us composition was developed based on the pharmacological properties of its constituent of the medicinal plants. So, Siberian ginseng, Rhodiola rosea and - invigorating and restorative effect, increase physical and mental efficiency; licorice - has a broad spectrum of pharmacological activity, including and expectorant action; thyme - has anti-inflammatory and antibacterial action; blueberry - has tonic properties, and is plant.

For research of plant collection prepared broth in a ratio of 1:10. The recommended human dose: 1 g (1/2 tsp) pour 100 boiling water, leave for 10-15 minutes, drain. Take 100 ml of 1 times in the morning for 30 minutes before eating. For experimental animals dose of 5 ml of broth at the animal.

Experimental work on mice lines NEA; F 1 (571/6) both sexes weighing 20-22, Experiments carried out in accordance with «Rules of work with use of experimental animals» Appendix to order of Ministry of health USSR №755 from 12.08.77, and «Rules of the European Convention for the protection of vertebrate animals used for experimental and other scientific purposes».

Statistical processing of the obtained data was performed by the generally accepted method of using the criterion of the Mann-Whitney (V.I. Sergienko, Bondareva I.B. Mathematical statistics in clinical studies. M., 2000. - 236 C.). Differences was considered significant with a probability of 95% (P<0.05).

Determination of acute toxicity adaptogenic remedy. Experiments were carried out on mice CBA both sexes weighing 18-20, the Acute toxicity of the adaptogenic remedy was determined using the method of Cerberus (Belenky DANILEVSKY Elements of the quantitative evaluation of the pharmacological effect. - HP, 1963. - 148 S.) when his single intragastric and intraperitoneal in the form of broth in doses of 1.0 to 395,0 ml/kg of animal weight. The final injected volume animals amounted to 1.0 ml/kg of Animal control groups received of distilled water. Animal watching carried out within 14 days from the moment of introduction of the means test. During the entire period of the experiment observed the General condition and behavior of animals, recorded the visible signs of intoxication and the number of killed animals with examination of internal organs and histological examination of the vital organs mortality.

It is established that intragastric and intraperitoneal injection of adaptogenic remedy in volume of 1,0-395 ml/kg did not cause death of animals during the entire period of observation. In animals treated with the test tool, and is not celebrated visible signs of intoxication; behavioural reactions and General condition is not different from that of the control group animals; animal experimental groups remained active, well-accepted food, the chair was normal for the whole observation period. The obtained data allow to carry adaptogenic remedy to a group of practically is not toxic substances according to the classification Sidorova K.K. (Sidorov K.K. ON the classification of toxicity poisons when parenteral ways. // Toxicology new industrial chemicals. - M, 1973. P.47-51).

Study of the influence of adaptogenic remedy on the overall physical endurance test animals.

Experiments were carried out on mice CBA both sexes weighing 19-20, To determine the total physical endurance a commonly used technique in a swimming pool with water temperature 20,0±0.5 degrees C with cargo amounting to 5% of body weight in accordance with the guidelines set out in the guide (Determination of the safety and efficacy of biologically active additives to food. Methodical instructions. - M, 1999. - 86 C.). To determine effect, a decoction of the investigated funds administered intragastrically once for 1 h before testing in volume 0,5; 1,0; 3,0; 5.0 and 7.0 ml/kg. With the study of time - dependent effect, the drug was administered prophylactically once in the amount of 3.0 ml/kg per 0,5; 1,0; 3,0; 6,0 and 24.0 hours before the test. To investigate the dependence of the multiplicity of the introduction, the test tool was administered prophylactically in the volume of 1.0, 3.0 and 5.0 ml/kg for 3, 7 and 14 days 1 once a day for 30 minutes before feeding. Animals of the control group received of distilled water. As a comparison drug hereinafter used solution Eleutherococcus extract in volumes 3.0 and 5.0 ml/kg of a General physical endurance animals was determined by means of swimming of animals to full exhaustion criterion which served a 10-second dive of the animal is submerged. The obtained data are given in tables 1-6.

As follows from the data given in table 1, one introduction of the means test white mice in volumes of 0.5 and 1.0 ml/kg had no significant effect on the length of the voyage animals with the use of the funds in the amount of 3.0 ml/kg g there was an increase of the total physical endurance by 32% compared with the mice in the control group. If you increase the amount of the means test, there was an increase his activity. So, with the introduction of volume of 5.0 ml/kg, duration of the voyage animals of the experimental group increased on average by 45% compared with those in the control group mice. When Photohem introduction of the preparation in higher doses (5.0 and 7.0 ml/kg) revealed similar adaptogenic action: physical performance increased on average by 40-45% compared with the control group animals. The effectiveness of the means test was similar to that of the comparison drug - Eleutherococcus extract in similar doses. Given that the voyage of animals treated with the test tool in the amount of 3.0 ml/kg, were not statistically different from that in mice treated it in volumes 5.0 and 7.0 ml/kg, in further experiments, as an experimental therapeutic been used volume of the investigated products, corresponding to 3.0 ml/kg

The impact of adaptogenic remedy on the overall physical endurance of the white mice depending on the input volume (M±SD)

Groups of animals

Volume, ml/kg

The length of the voyage, min

Control (N 2 O)

15,9±1,63

Experienced 1 (test tool)

16,2±1,45

Experienced 2 (test tool)

17,3±1,36

Experienced 3 (test tool)

21.4 ħ 1,54*

Experimental 4 (test tool)

25,3±1,41*

Experienced 5 (test tool)

24,3±1,67*

Experienced 6 (Siberian ginseng)

20,3±1,18*

Experienced 7 (Siberian ginseng)

21,2±of 1.59*

Legend: * - here and further the values significantly different from the data of the control group at P<0.05.

The impact of adaptogenic remedy in the amount of 3.0 ml/kg for the total physical endurance of the white mice depending on the time of administration (M±SD)

Groups of animals

Time after introduction, h

The length of the voyage, min

Control (N 2 O)

15,9±1,63

Experienced 1 (test tool)

21.4 ħ 1,54*

Experienced 2 (test tool)

23,1±1,32*

Experienced 3 (test tool)

21,6±1,23*

Experimental 4 (test tool)

20,3±1,42*

Experienced 5 (test tool)

15,2±1,34

From the data given in the specified the above table shows, that the stimulating effect of the test drug is as early as 30 minutes after a single injection in the amount of 3.0 ml/kg: the length of the voyage white mice increased by 34% in comparison with the control. Through 1,0 hour after drug administration operability white mice increased by almost 40% and remained at this level for 3 hours, after which adaptogenic effect began to decline: in 6 hours time sailing mice experimental group exceeded the data in the control of only 32%, and after days after drug administration operability of the animals of the experimental group was reduced to the level of the mice in the control group.

In the study of the dependence of the pharmacological effect of the drug from the multiplicity of its introduction established that repeated preventive his introduction to white mice accompanied by the increase of activity (table 3).

The impact of adaptogenic remedy on the overall physical endurance of the white mice depending on the multiplicity of the introduction (M±SD)

Groups of animals

Volume, ml/kg

The length of the voyage, min

during the 3-day introduction

in 7-day introduction

when 14-day introduction

Control (H 2 O)

18,7±1,47

20,2±1,32

21,54±1,63

Experienced 1 (test tool)

28,2±1,43*

29,3±1,47*

31,5±1,74*

Experienced 2 (test tool)

30,2±1,84*

37,2±1,89*

38,5±1,46*

Experienced 3 (test tool)

32,7±1,39*

38,3±2,12*

39,7±2,26*

Experimental 4 (Siberian ginseng)

30,1±1,46*

33,3±1,45*

34,3±2,04*

As follows from table 3, the most pronounced increase physical endurance noted for its 7-day introduction in volumes 3.0 and 5.0 ml/kg: the length of the voyage mice these groups experienced increases accordingly by 84% and 90% compared with the control group animals. Somewhat less pronounced impact of medicine has at its introduction in the course of 3 days, and the introduction within 14 days of its efficacy was similar those in the introduction for 7 days. The activity of the means test with multiple introduction surpassed that in comparison drug - extract of Siberian ginseng.

Thus, the obtained data testify that the test tool provides a stimulating effect on the overall physical endurance, is characterized by the predominance of aerobic processes of energy supply to the tissues. It is established, that after acute administration, the most pronounced adaptogenic effect the drug has volumes 3.0-5.0 ml/kg in giving 1.0 hours prior to the study; its efficiency increases with repeated preventive introduction: the most pronounced increase physical endurance noted for its 7-day prophylactic introduction in the amount of 3.0 ml/kg

Example 2. Study of the influence of adaptogenic remedy on the speed endurance test animals.

Experiments were carried out on mice CBA both sexes weighing 18-20, The impact of the means test on high-speed physical endurance was determined by the duration of the running animals of the 10-track treadmill with a speed of paintings treadmill 40 m/min (Determination of the safety and efficacy of biologically active additives to food. Methodical instructions. - M, 1999. - 86 C.). Investigational tool was administered intragastrically in the amount of 3.0 ml/kg once for 1 h before the test, as well as oseltamivir repeatedly, within 7 days in the specified volume 1 once a day for 30 minutes before feeding. Animals of the control group was administered intragastrically a similar volume of distilled water. As a comparison drug used solution Eleutherococcus extract in the amount of 3.0 ml/kg of high-Speed physical endurance estimated duration running animals to full exhaustion criterion which served a 10-second finding of the animal on the electric grid treadmill under voltage 70 Century, the Obtained data are given in table 4.

The impact of adaptogenic remedy on the fast physical endurance of the white mice (M±SD)

Groups of animals

The duration of the races,

after acute administration

in 7-day introduction

Control (N 2 O)

224,1±13,8

226,7±18,7

Experienced 1 (test tool)

238,3±17,4

303,3±24,6 *

Experienced 2 (Siberian ginseng)

235,5±21,1

to 274.6±19,2 *

As follows from the data given in table 5, a one-off introduction of this tool in the specified volume, as well as the comparison drug has not had a significant impact on high-speed physical endurance of the white mice, the duration of the running animals of the experimental group is not statistically differ from that of the animals of the control group (p & GE 0,05).

It is established that repeated preventive introduction of the means test within 7 days was accompanied by a significant increase in speed and endurance, as evidenced by increase of the duration of the running animals of the experimental group by 34% compared with the mice in the control group. The effectiveness of the means test surpassed that in Eleutherococcus extract. Thus, the obtained data testify that the trial medication in the amount of 3.0 ml/kg increased the speed physical endurance, is characterized by the predominance of anaerobic processes in the tissues, only when multiple administrations.

Example 3. We studied the influence of adaptogenic remedy on the speed endurance against the background of the dosed physical loads. Experiments were carried out on mice CBA both sexes weighing 18-20, Pre-dosed physical activity carried out by means of compulsory running animal in a treadmill at a tape speed of 28 m/min for 3 minutes Animals that received a preliminary exercise, distributed on 4 subgroups. The first group proposed tool introduced 3.0 ml/kg), once for 1 hour before the examination, and the second group - just one hour before the test within 7 days. As a comparison drug used solution Eleutherococcus extract in the amount of 3.0 ml/kg, the same scheme (group 3 - once, group 2 - 7 days). Animals of the control group was administered intragastrically a similar volume of distilled water.

In the first day of the duration of the run was 4.5 minutes, in the next 7 days duration running consistently increased by 0.23 min and was 5.7 minutes In 1 and group 3 after acute administration of drugs showed an increase in the duration of running with the introduction of the proposed funds for 23% and the introduction of Eleutherococcus - on 20%. After seven days of taking the drugs shown to increase speed endurance when accepting the proposed funds to 86% compared with the control group. Eleuterococus also increased the speed endurance 72%

On the 7th day, after 1 h after the last injection of the specified means, determined the speed endurance on duration of run of the treadmill to full exhaustion. The obtained data are given in table 5.

The impact of adaptogenic remedy on the speed endurance of mice against the background of the preliminary physical exercises (M±SD)

Groups of animals

The duration of the races,

once you load

during the 7-day load

Control (N 2 O), (n=20)

272,1±16,3

293,3±21,2

Pilot (test method), (n=20)

337,3±18,9*

545,3±23,6*

Intact (n=20)

329,9±19,5*

504,7±24,9*

The data in table 6 indicate that a single injection of the specified funds in the amount of 3.0 ml/kg against the background of a single dosed loads, assisted protective action, preventing a decline in physical health mice experimental group.

These data suggest that the introduction of the means test in the specified volume on the background of the dosed physical loads has adaptogenic effect, preventing the development of fatigue after a single load. A more pronounced adaptogenic effect test tool is repeated when a background in the daily dosed physical loads.

Study of the influence of the means test on power endurance test animals.

Experiments were carried out on mice CBA both sexes weighing 18-20, In the experiments used a model «hanging on a pole». Animals of the experimental group was administered intragastrically solution of the specified funds in the amount of 3.0 ml/kg once for 1 hour before testing, and many times within 7 days in the specified volume 1 once a day for 30 minutes before feeding. Animals of the control group was administered intragastrically a similar volume of distilled water. The impact of the means test on power endurance was determined by time «vis animals on a pole», from the start of the hold until the fall. Data of the experiment are given in table 6.

The impact of adaptogenic remedy on power endurance white mice (M±SD)

Groups of animals

Duration hanging on a pole, min

after acute administration

in 7-day introduction

Control (H 2 O, n=20)

15,3±1,52

16,2±1,24

Experienced 1 (test tool, n=20)

22,6±1,63*

28,2±1,35*

Experienced 2 (Eleutherococcus, n=20)

21,9±1,33*

25,3±1,37*

As follows from the data given in table 8, after acute administration of the funds in the amount of 3.0 ml/kg, time vis mice experimental group increased by 46% compared with those in the control group animals. Repeated introduction of the means test is accompanied by a more pronounced increase of power endurance animals, as evidenced by the increase in the duration of vis mice experimental group in average 75% in comparison with the animals of the control group. The effectiveness of the means test was similar to that of the comparison drug.

Tool that has activity characterized by the fact that it contains the roots of Eleutherococcus senticosus, the roots of Rhodiola rosea, Ural licorice roots, shoots bilberry, grass creeping thyme in the following ratio, mass%:

the roots of Eleutherococcus senticosus

the roots of Rhodiola rosea

Ural licorice roots

bilberry shoots

grass creeping thyme