RU2233168C2 - Composition of components for preparing curative elixir "doktor petrov" - Google Patents

Abstract

FIELD: medicine, phytotherapy, pharmacy.

SUBSTANCE: invention relates to the development of agents of vegetable origin. Invention proposes a composition for preparing elixir that contains the following components: rowan melanocarpous (aronia) dry fruits, wild rose fruits, linden flowers, common wormwood herb, Inonotus obliquus, black pepper, nutmeg, nettle leaves, prune fruits, propolis, aloe juice or Aloe arborescent dry leaves, bee honey, ginseng roots, purple coneflower herb, marjoram herb, hawthorn fruits, Bergenia pacifica rhizomes, Saint-John's-wort herb, dried grape, and sugar color or sugar, and 40% ethyl alcohol. Elixir elicits adaptogenic and general tonic effect in intensive and prolonged nervous-psychotic and physical loadings. Elixir can be used for prophylactic aim in first symptoms of cold diseases.

EFFECT: valuable medicinal properties of elixir.

20 tbl, 3 ex

Description

The invention relates to the pharmaceutical industry and medicine and can be used to prepare a therapeutic elixir based on medicinal plant materials.

A known composition with vitamin activity, containing rose hips, mountain ash, currant leaves, perforated St. John's wort grass and peppermint [1].

The disadvantage of this composition is the relatively narrow spectrum of action, it does not have neurotonizing, anti-alcohol, nootropic, antidiarrheal activity, the ability to attenuate manifestations of radiation sickness, stress-protective, immunostimulating properties, while it has a relatively short shelf life; there are no data on antioxidant activity and the ability of the composition to increase physical performance.

The Crimean balm composition enriched with vitamins is also known, which includes 36 types of medicinal plant materials, including rose hips, wormwood, lemon balm, narrow-leaved lavender, etc. [2, 3].

This composition was initially declared as a tonic and prophylactic in the food industry. However, as a result of clinical and physiological tests, it was identified as a phytoadaptogen, a radio and stress-protective agent that helps to increase the body's adaptation and resistance. The specified balm helps increase muscle performance, resistance to hypoxia, accelerate the elimination of hydrophilic and hydrophobic xenobiotics.

A disadvantage of the known Crimean balm composition is that its adaptogenic, immuno-and radioresistogenic properties are manifested only in combination with the balneological factor of the Truskavets resort, i.e. in certain special cases. The drug does not have antioxidant, anti-alcohol, nootropic, antidiarrheal properties.

Known means for the prevention and correction of functional disorders associated with exposure to the body of various adverse factors, including ionizing and radiation radiation [4]. This product contains concentrated grape juice, apple and chokeberry-rowanberry extracts, water-alcohol extracts from dogrose and hawthorn, as well as aralia and eleutherococcus.

This composition does not have immunostimulating activity, which makes it less valuable in environmentally unfavorable zones, for example, Belarus, where an environmentally unfavorable environment leads to a decrease in immunity, weakening the body's resistance to various types of infections, including viral ones. In addition, the claimed composition does not possess a number of other types of activity (antioxidant, anti-alcohol, antidiarrheal, nootropic, neurotonizing, actoprotective, stress-protective).

Also known is the elixir "Evalar" (Russian Federation), which is an extract from a mixture of 19 types of plant medicinal raw materials: rhizomes and roots of Eleutherococcus, rhizomes and roots of raponticum safflower, licorice roots perforated, St. John's wort, Siberian pine pine seeds (pine nuts) thalli of kelp, flowers of sandy immortelle, blood-red hawthorn fruits, pharmacy chamomile flowers, large plantain leaves, yarrow grass, peppermint leaves, rhizomes and root Rhodiola rosea, Rowan fruits, cinnamon rose hips, seed coriander fruits, pantocrine, horse chestnut fruits, cranberry fruits, with the addition of natural honey, sugar, elixir tint, ethyl alcohol, purified water. Elixir "Evalar" is recommended for use in medical practice as a tonic, a drug that increases physical and mental performance. There is no information about the presence of the claimed composition immunostimulating, antioxidant, stress-protective, anti-alcohol, antidiarrheal activity, the ability to attenuate manifestations of radiation sickness [8].

Known means for the normalization of immunological reactivity of the body, containing biologically active substances of natural origin. At the same time, the following composition of natural origin is proposed: ethyl alcohol, 50% rhizome of common calamus (1.5-15.0), rhizome rhizome erect (1.5-15.0), large celandine grass (1.0-10.0 ), grass of St. John's wort perforated (1.0-10.0), inflorescences of linden (1.0-10.0), rhizomes and roots of elecampane high (1.5-15.0), grass of a three-part succession (0.5- 5.0), oak bark (2.0-20.0), rose hips (4.0-40.0), chokeberry fruits (2.0-20.0), hawthorn fruits (4.0-40 0), fruits of common viburnum (1.5-15.0), fruits of thyme ordinary (1.0-10.0), wormwood herb (0.5-5.0), inflorescence of chamomile aries (1.0-10.0), sweet clover herb (1.0-10.0), dioecious nettle leaves (2.0-20.0), natural honey (1.0-10.0), concentrate apple juice (1.0-10.0), grape juice concentrate (1.6-16.0) [5]. However, there is no information about the ability of this balm to weaken the manifestations of radiation sickness, its neurotonizing, anti-alcohol, nootropic, antidiarrheal activity, antioxidant, actoprotective, stress-protective properties.

Also known therapeutic balm "Tone", which has adaptogenic and antiviral properties, which is an active inducer of interferon in the blood. The “Tonus” balm includes the following components: yarrow herb (0.1-10.0), calamus rhizome (0.1-10.0), three-leaved shift leaves (0.1-5.0), wormwood herb (0 , 01-0.5), linden flowers (1.0-10.0), elecampane rhizome (0.01-5.0), grass of the mountaineer bird (0.1-5.0), hop haplotype (0, 1-5.0), chokeberry (chokeberry) fruits (1.0-10.0), oak bark (1.0-10.0), propolis (0.1-10.0), black pepper (0 , 01-2.0), cardamom (0.1-2.0), natural coffee (0.1-2.0), prune fruits (1.0-10.0), dried grapes (1.0- 10.0), ethyl alcohol 40%. However, it does not have neurotonizing, actoprotective, antioxidant, anti-alcohol, antidiarrheal, nootropic properties, the ability to attenuate manifestations of radiation sickness [6].

Closest to the claimed elixir is the “Vitaminized" balm (prototype) [7] based on a composition with vitamin activity, which is used to correct emerging pathological disorders in the human body in an unfavorable environmental situation. The preparation includes ingredients of natural origin: chokeberry (chokeberry) fruits (1.0-10.0), rose hips (1.0-10.0), linden flowers (0.5-10.0), wormwood herb ( 0.01-0.03), oak bark (0.1-10.0), chaga (0.1-5.0), black pepper (0.01-0.5), nutmeg (0.1 -2.0), nettle leaves (0.5-10.0), prune fruits (1.0-10.0), propolis (0.5-3.0), aloe juice (1.0-20, 0), bee honey (1.0-20.0), with the addition of ethyl alcohol 40%. Vitaminized balm is characterized by the presence of interferon-inducing activity, but does not have neurotonizing, anti-alcohol, nootropic, antidiarrheal activity, the ability to weaken the manifestations of radiation sickness, antioxidant, actoprotective, stress-protective properties [7].

The aim of the present invention is the creation of such a composition of ingredients for the preparation of an elixir, which will ensure that it has neurotonizing, anti-alcohol, nootropic, antidiarrheal activity, the ability to weaken the manifestations of radiation sickness, antioxidant, actoprotective, stress-protective, immunostimulating properties. The presence of these types of activity is especially important for places of residence with adverse environmental conditions.

The problem is solved by the additional, in comparison with the prototype, the introduction of the following components: the roots of Belarusian ginseng cultivation, herbs Echinacea purpurea, marjoram, dried grapes, hawthorn fruit, incense rhizomes, St. John's wort.

Ginseng roots, propolis, chaga, incense rhizomes, nutmeg, chopped black pepper. Echinacea grass in an amount of 15 g, dry aloe vera leaves in an amount of 2.5 g or aloe juice in an amount of 150 g, St. John's wort grass in an amount of 5.0 g, hawthorn fruits in an amount of 5.0 g, fruits of chokeberry (chokeberry) in 25 g, rosehips in the amount of 50 g, linden flowers in the amount of 10 g, wormwood grass in the amount of 0.25 g, nettle leaves in the amount of 10.0 g, natural honey in the amount of 25 g, oregano grass in the amount of 0, 5 g, dried grapes in an amount of 20.0 g, prune fruits in an amount of 50 g and ground ginseng roots in an amount of 0.3 g, propolis in an amount of 2.5 g, chaga in an amount of 5.0 g, nutmeg in an amount of 2.5 g and black pepper in an amount of 0.5 g are loaded into a container and poured 645 ml of ethyl alcohol (46 ± 2)%.

The extraction is carried out at room temperature for 29-30 days. During the infusion process, the mass in the container is periodically mixed. Upon completion of the extraction process, the alcoholic extract is filtered, then the filtered extract is mixed with sugar color in an amount of 225 g and kept in the apparatus for 2 days. 1000 ml of elixir are obtained.

Moreover, the composition itself is declared in the following proportions:

ginseng roots 0.1-0.6 g

Echinacea herb 1.5-30.0 g

propolis 0.25-2.5 g

dry aloe vera leaves 0.25-2.5 g

or aloe juice 15.0-150.0 g

Chaga 0.5-10.0 g

Rhizomes of Badanas 0.5-10.0 g

St. John's wort grass 0.5-10.0 g

fruits of hawthorn 0.5-10.0 g

dry chokeberry fruits (chokeberry) pressed dry 2.5-50.0 g

rose hips 5.0-100.0g

linden flowers 1.0-20.0 g

wormwood herb 0.025-0.5 g

nettle leaves 1.0-20.0 g

natural honey 2.5-50.0 g

oregano grass 0.05-1.0 g

dried grapes 2.0-40.0 g

Nutmeg 0.25-5.0 g

prune fruits 5.0-100.0 g

black pepper 0.05-1.0 g

sugar 150.0 g

or sugar color 225 g

ethyl alcohol 40% to obtain 1000 ml of elixir

Example 1

ginseng roots 0.1 g

Echinacea herb 1.5 g

propolis 0.25 g

aloe juice 150.0 g

Chaga 0.5 g

Rhizomes of Badanus 0.5 g

St. John's wort grass 0.5 g

hawthorn fruit 0.5 g

dry chokeberry (chokeberry) fruits pressed dry 25.0 g

rose hips 50.0 g

linden flowers 10.0 g

wormwood herb 0.25 g

nettle leaves 10.0 g

natural honey 25.0 g

oregano grass 0.05 g

dried grapes 2.0 g

nutmeg 0.25 g

prune fruit 50.0 g

black pepper 0.5 g

sugar 150.0 g

or sugar color 225 g

ethyl alcohol 40% to obtain 1000 ml of elixir

Example 2

Take, wt.%:

ginseng roots 0.3 g

echinacea herb 15.0 g

propolis 2.5 g

aloe juice 150.0 g

Chaga 5.0 g

Rhizomes of Badanas 5.0 g

Hypericum herb 5.0 g

hawthorn fruit 5.0 g

dry chokeberry (chokeberry) fruits pressed dry 25.0 g

rose hips 50.0 g

linden flowers 10.0 g

wormwood herb 0.25 g

nettle leaves 10.0 g

natural honey 25.0 g

oregano grass 0.5 g

dried grapes 20.0 g

nutmeg 2.5 g

prune fruit 50.0 g

black pepper 0.5 g

sugar 150 g

or sugar color 225 g

ethyl alcohol 40% to obtain 1000 ml of elixir

Example 3

Take, wt.%:

ginseng roots 0.6 g

echinacea herb 30.0 g

propolis 2.5 g

dry aloe vera leaves 2.5 g

Chaga 5.0 g

Rhizomes of Badan 10.0 g

St. John's wort grass 10.0 g

hawthorn fruit 10.0 g

dry chokeberry (chokeberry) fruits pressed dry 25.0 g

rose hips 50.0 g

linden flowers 10.0 g

wormwood herb 0.25 g

nettle leaves 10.0 g

natural honey 25.0 g

oregano grass 1.0 g

dried grapes 40.0 g

nutmeg 2.5 g

prune fruit 50.0 g

black pepper 0.5 g

sugar 150.0 g

ethyl alcohol 40% to obtain 1000 ml of elixir

According to examples 1, 2, 3, a composition is prepared to obtain an elixir, which is a drug in the form of a clear liquid of dark brown color with a pleasant aroma.

Elixirs obtained from the composition according to examples 1, 2, 3, have the following indicators (table. 1).

Elixir has a wide spectrum of action and can be used in adults as a therapeutic and prophylactic adaptogenic and restorative agent; with intensive and prolonged neuropsychic stresses with the goal of quick and complete restoration of working capacity, with asthenic manifestations of various origins, during convalescence after chronic diseases, in patients with initial manifestations of cerebrovascular insufficiency (decreased working capacity, increased fatigue, impaired memory and attention); with a preventive purpose at the first signs of colds, in the most critical times of the year, when conducting antibiotic therapy, radiation and chemotherapy and other conditions accompanied by a decrease in the functions of the immune system; possesses antidiarrheal activity; exhibits anti-alcohol properties and is characterized by the ability to weaken the effects of alcohol intoxication; can be used as a means of preventing negative manifestations of stress, including stress-induced erosive and ulcerative lesions of the stomach.

In experimental studies, it was found that the created elixir "Doctor Petrov" (hereinafter referred to as the elixir) has a wide spectrum of biological activity due to the presence of highly active plant components in its composition. It is characterized by neurotonizing, anti-alcohol, nootropic, antidiarrheal activity, the ability to weaken the manifestations of radiation sickness, antioxidant, actoprotective, stress-protective, immunomodulating properties.

The elixir differs from all the above-described herbal preparations, including the prototype, in the presence of anti-alcohol, antioxidant, antidiarrheal, nootropic effects. The elixir differs from the prototype in that it has neurotonizing, anti-alcohol, nootropic, antidiarrheal activity, the ability to weaken the manifestations of radiation sickness, antioxidant, actoprotective, stress-protective properties (table. 2).

1. NEUROTONIZING PROPERTIES

It has been established that a dealcoholized elixir with a single oral administration in doses corresponding to 3, 10 and 30 ml / kg of an alcohol-containing drug has a neurotonizing effect. This can be judged by the absence of loss of the orthostatic reflex in 10-40% of mice of the experimental group and by a significant shortening of the duration of ethanol anesthesia in mice treated with elixir 1 hour before the introduction of ethyl alcohol in a narcotic dose (Table 3).

The dealcoholized elixir was shown to have a distinct neurostimulating effect in intact mice, evaluated by the effect on the parameters of motor activity (according to the results of actometry). The elixir was administered 30 minutes before testing in doses corresponding to 1, 3 and 10 ml / kg of the native drug.

It was found that the drug increases horizontal and vertical motor activity and the number of runs, that is, it promotes the activation of motivated motor behavior. The non-alcoholic base of the elixir has a moderately pronounced stimulating effect on the central nervous system, without causing the phenomena of hyper-excitation and side effects characteristic of neurostimulants of a mobilizing and depleting type of action.

2. ANTI-ALCOHOL PROPERTIES

The elixir weakens the inhibitory effect of ethanol on the central nervous system, and also reduces the neurotoxic and somatic symptoms of the aftereffect of ethyl alcohol, in particular, such as depression of spontaneous motor activity and a decrease in physical endurance of animals; prevents the development of post-alcohol amnesia.

a) Decrease in the neuroprotective effects of alcohol under the influence of an elixir.

In order to identify the direct anti-alcohol effect of the elixir, comparative tests of the narcotic effect of the native elixir and 40% ethanol were carried out.

Native elixir contains 40% ethyl alcohol. The animals of the experimental group were injected with an alcohol-containing elixir, and the dose and concentration of ethanol administered to them corresponded to the dose and concentration of ethanol administered to mice of the control group (8 and 10 ml of ethyl alcohol 40%). It was found that the plant components of the elixir significantly attenuate the neurodepressing effect of the ethanol contained in the elixir: 40% ethanol has a significantly greater narcotic effect than ethanol at the same dose and the same concentration in the composition of the elixir (Table 4). In 40% of the mice of the experimental group that were injected with the elixir, the lateral position did not occur, and the duration of anesthesia in the remaining animals of this group was 30% less than in the control (P <0.05).

b) The ability of the elixir to reduce the neurotoxic and somatic symptoms of the aftereffect of ethanol (depression of spontaneous motor activity and a decrease in the physical endurance of animals).

The dealcoholized elixir, when administered orally at a dose corresponding to 10 ml / kg of the native elixir, eliminates the depression of spontaneous motor activity in mice.

To evaluate the anti-alcohol effect of the elixir, mice of the first experimental group 1 day before testing were injected with ethanol at a dose of 3 ml / kg, and animals of the second (experimental) group were given ethanol and a dealcoholized elixir (10 ml / kg in terms of the native drug). The indices of motor activity were evaluated the next day using an Opto-Varimex actometer (10-minute test).

The research results are presented in table. 5.

The data given in table. 5, indicate a pronounced inhibition of all parameters of psychomotor activity in animals treated with ethanol, which indicates a delayed neurodeceptive effect of the latter. The introduction of the elixir almost completely eliminates post-alcohol depression and ensures the normalization of the parameters of the motor activity of animals.

To assess the ability of the elixir to interfere with the hypodynamic effect of alcohol intoxication and restore physical endurance and performance, experiments were performed on mice using a modified Kiplinger instrumental test, which allows to evaluate the swimming speed of trained animals with repeated swimming of the standard distance. 1 day before testing the physical performance of the animals of the active control group, ethanol was administered orally in a narcotic dose (3 ml / kg), and the animals of the experimental group were given ethanol and dealcoholized elixir in a dose corresponding to 30 ml / kg of the native drug.

The research results are presented in table. 6 in the form of relative indicators, expressed as a percentage of control.

It was found that the administration of a narcotic dose of ethanol 1 day before testing leads to the development of a pronounced hypodynamic state in mice, which is manifested by a decrease in all parameters of physical performance. The simultaneous administration of a dealcoholized elixir provides a pronounced protective effect in relation to the hypodynamic aftereffect of alcohol.

c) The ability of the elixir to prevent the violation of the cognitive functions of animals caused by the preliminary introduction of ethanol.

The protective effect of the elixir on the cognitive functions of animals against the background of alcohol intoxication was evaluated using the methodology for developing the conditioned active avoidance reflex (URAI) in Shuttle shuttle chamber. The elixir was administered to rats for 5 days prior to oral testing at a dose corresponding to 10 ml / kg of the native elixir; animals in the control group were given placebo. The cognitive functions of animals were evaluated against the background of continued daily administration of the elixir. The learning ability of rats was tested on the 6th day from the start of drug administration, and the reproduction of URAI was carried out on the 9th and 12th day of administration (i.e., 3 and 6 days after the first training cycle). Then, ethanol (3 ml / kg) was intragastrically administered to the rats of the experimental and control groups, and on the next (13) day, the ability to reproduce URAI was retested. The state of cognitive functions after the amnesic action of ethanol was evaluated by the duration of the latent period of reproduction of the conditioned reflex, the number of combinations required to reach the level of 50% of correct answers (N), and the regression of the ratio of the number of successful solutions to the problem (avoiding electric shock) to unsuccessful.

The experimental results are presented in table. 7, from which it follows that ethanol (3 ml / kg), administered against the background of the developed conditioned reflex the day before testing, violates the ability of animals to reproduce URAI.

The preliminary appointment of the elixir ensures the safety of the developed reflex at the initial (determined before alcoholization) level.

3. NUTROPIC PROPERTIES

The effect of dealcoholized elixir on cognitive function in intact animals and in conditions of ethanol-induced amnesia was studied in experiments on rats using the technique of developing a conditioned active avoidance reflex (URAI) in Shuttle shuttle chamber.

a) a study of the effect of elixir on cognitive function in intact animals in the conditions of single and multiple administration.

The effect of a single administration of a dealcoholized elixir on the ability to learn, maintain and reproduce conditioned reflex skills was evaluated in experiments on rats in the test for the development of a conditioned passive avoidance reflex (URAI).

The effect of the elixir on the cognitive functions of animals in a single administration was evaluated by its effect on the learning ability of rats: data on the development of URAI on the first day of testing were taken into account. The dealcoholized elixir was administered once orally in doses corresponding to 1, 3 and 10 ml / kg of the native elixir 1 hour before the development of the conditioned reflex. Control animals received placebo under similar conditions.

In addition, the effect of the elixir on the level of consolidation and the ability of animals to extract information was recorded: these indicators were evaluated by the ability to reproduce URAI on the second and fourth days of testing.

The dealcoholized elixir was administered orally at the same doses 1 hour before each test. Control animals received a placebo.

The research results presented in table. 8, indicate that a single administration of dealcoholized elixir in doses of 3 and 10 ml / kg (in terms of the native elixir) 1.5-2 times increases the learning ability of rats. The introduction of a dealcoholized elixir in doses corresponding to 1.0, 3.0 and 10.0 ml / kg of an alcohol-containing drug provides a more successful, as compared to control, fixation and reproduction of conditioned reflex skill during testing on days 2 and 4. In addition, the drug increases the reaction rate of animals to the presentation of a conditioned stimulus (table. 8).

B) The effect of repeated administration of a dealcoholized elixir on the ability to learn, maintain and reproduce conditioned reflex skills was evaluated in experiments on rats in the test for the development of a conditioned passive avoidance reflex (URAI).

The dealcoholized elixir was administered to animals for 5 days prior to oral testing at a dose corresponding to 10 ml / kg of the native elixir; animals in the control group were given placebo. The cognitive functions of animals were evaluated against the background of continued daily administration of the elixir.

The ability of rats to learn was tested on the 6th day from the start of drug administration, and the level of consolidation and the ability to extract information (reproduction of URAI) was evaluated on the 9th and 12th day of administration (i.e., 3 and 6 days after the first training cycle).

It was established that repeated administration of a dealcoholized elixir promotes an increase in the rate of URAI production, as well as more effective consolidation and reproduction of the developed skill in comparison with the control (Table 9).

b) Antiamnestic properties of a dealcoholized elixir under conditions of impaired reproduction of the conditioned reflex of active avoidance induced by ethanol.

It was found that the administration of ethanol to rats in a narcotic dose (3 ml / kg) on the eve of reproduction of the developed URAI worsens cognition performance, increasing 1.5 times the number of test cycles required to achieve a level of 50% learning. The dealcoholized elixir with a preliminary 12-day oral administration in a dose corresponding to 10 ml / kg of the native preparation completely eliminates the effects of alcohol that disrupts the processes of reproduction of conditioned reflexes (Table 7).

In this example, ethanol can be considered as an amnesting factor, and the action of the elixir as an antiamnestic.

4. ANTI-DIARY PROPERTIES

The elixir exerts an antidiarrheal effect on two experimental models of diarrhea: caused by intragastric administration of castor oil and total γ-irradiation.

a) Antidiarrheal effect of the elixir on the model of dyspeptic disorders caused by intragastric administration of castor oil.

Castor diarrhea was caused by intragastric administration to mice of 0.3 ml of heated castor oil. Placebo and dealcoholized elixir at a dose corresponding to 10 and 30 ml / kg of the native drug were administered 30 minutes before the experiment. For 90 minutes, the time of onset and end of diarrhea, as well as the intensity and frequency of cases of diarrhea, were taken into account.

It was found that in control mice in 100% of cases castor oil causes intense diarrhea. Preliminary administration of the elixir in a dose corresponding to 30 ml / kg of the native preparation completely prevents the onset of diarrhea in 40% of mice (P <0.05), while in the remaining animals it significantly delays its development and reduces the duration, reduces the number and volume of bowel movements (Table. 10). With the introduction of an elixir in a dose corresponding to 10 ml / kg of an alcohol-containing drug, diarrhea is also prevented in 40% of cases (P <0.05), but its intensity is suppressed less.

b) The effect of the elixir on post-radiation diarrhea caused by total γ-radiation.

The effectiveness of the elixir in the model of postradiation diarrhea was tested in experiments on mice and rats irradiated with totally γ-rays of Co ⁶⁰ at doses of 200 Gy and 300 Gy, respectively, with a dose rate of about 90 Gy / min. Post-radiation diarrhea occurs within 1 hour after acute radiation exposure in high doses and is caused by the excitation of peristaltic activity and a sharp increase in the secretion of water into the intestinal cavity.

Mice and rats were given placebo or a dealcoholized elixir in doses of 10 and 30 ml / kg of the native preparation 30 minutes before irradiation in the stomach. The presence and intensity of diarrhea within 2 hours of observation was taken into account. The research results are presented in table. 11, from which it follows that post-radiation diarrhea developed in the control in 100% of cases. Preliminary administration of elixir in doses corresponding to 10 and 30 ml / kg of the native preparation completely prevents the development of diarrhea in 30-50% of animals (P <0.05); in other animals, the introduction of the elixir weakens the intensity of diarrhea, delays its development and reduces the duration, reduces the number and volume of bowel movements.

Thus. The elixir has a pronounced antidiarrheal activity on diarrhea models of various genesis (castor and early postradiation diarrhea).

5. REDUCED MANIFESTATIONS OF RADIATING DISEASE

The effectiveness of the elixir as a means of attenuating the manifestations of radiation damage was evaluated in 2 series of experiments on mice subjected to γ-radiation at doses of 800 and 950 cGy with a radiation power of 50 cGy / min. The radiation doses used simulate mainly bone marrow (800 cGy) and mixed (bone marrow and gastrointestinal - 950 cGy) forms of radiation injury. Each series of experiments included 5 groups of animals: 1 - biological control, 2 - radiation + placebo, 3, 4, 5 - radiation + dealcoholized elixir in doses equivalent to 3, 10 and 30 ml / kg of the native drug, respectively. Elixir and placebo were administered intragastrically daily for 6 days after irradiation. The course of acute radiation sickness (ARS) was monitored by the survival of animals for 30 days and the dynamics of body weight with daily weighing.

The results of experiments with irradiation of mice at a dose of 800 cGy show that the introduction of an elixir contributes to the survival of totally irradiated animals (Table 12). In groups of animals treated with dealcoholized elixir in doses corresponding to 3, 10 and 30 ml / kg of the native drug, survival by 30 days was 20-50%, and in the control, 10%.

The introduction of elixir in all tested doses has a positive effect on the course of ARS, weakening the decrease in body weight of animals during the peak of bone marrow syndrome (the effect of the drug on the decrement of weight is statistically significant (P <0.05)).

In the 2nd series of experiments, the radiation dose was increased to 950 cGy in order to strengthen the intestinal component of radiation damage. In most of the control mice, a typical intestinal form of ARS occurred with a mortality of 4–5 days, and the remaining animals fell to 13 days with an average lifespan of 5.4 days (Table 13).

The introduction of an elixir in the conditions of this ARS model also significantly increases survival during the period of the greatest death of animals in the control group (from 6 to 12 days), causes a shift in the peak of mortality to 12 days and slightly increases the average life expectancy (Table 13). The ability of the elixir to weaken the manifestations of radiation sickness is also confirmed by the less pronounced decrease in body weight of experimental mice in the midst of ARS in the conditions of this model.

6. ANTIOXIDANT PROPERTIES

It is known that phagocytosis is accompanied by an intracellular oxidative burst with the formation of reactive oxygen species (ROS).

It has been established that the dealcoholized elixir has antioxidant properties that are detected by inhibition of the oxidative explosion of activated macrophages (MF). The antioxidant properties of the elixir were evaluated in two series of experiments: in vivo experiments with systematic repeated administration to rats and in vitro with direct exposure to isolated phagocytes of the elixir.

a) Antioxidant effects of elixir in vivo

Studies of the antioxidant activity of the elixir in in vivo experiments were carried out under conditions of preliminary 7-day administration of a dealcoholized drug in a dose corresponding to 10 ml / kg of the native elixir; animals in the control group were given placebo.

The antioxidant effect of the dealcoholized elixir was evaluated by the degree of inhibition of the zymosan-induced reaction of the oxidative explosion of peritoneal macrophages (MF). It was found that macrophages of animals that were systematically treated with a dealcoholized elixir at a dose corresponding to 10 ml / kg of the native preparation respond with a pronounced decrease in the chemiluminescent response to stimulation, that is, a reduced ability to generate ROS (Table 14). The elixir inhibition index of the MF oxidative reaction, calculated as the proportion of the decrement of luminol-dependent chemiluminescence (LHL) in the experimental group relative to placebo, is 51.3%.

b) Antioxidant effects of elixir in vitro

The antioxidant action of dealcoholized elixir was studied in vitro experiments on rat peritoneal macrophages. Activation of oxidative metabolism of MF was evaluated by the method of zymosanine-induced chemiluminescence in the presence of luminol. To the suspension of MF was added a dealcoholized elixir in final dilutions from 1 · 10 ^-8 to 1 · 10 ^-3 in volume. After registration of the baseline level of LHL, opsonized zymosan was added to each sample as an inducer of a respiratory explosion. Control samples for induced LHL did not contain an elixir, and an equivalent amount of Hanks medium was added to the control samples for spontaneous LHL instead of zymosan.

The experimental results are summarized in table. 15. It has been established that a dealcoholized elixir in a dilution corresponding to 1 ml / l (1 · 10 ^-3 ) of the native drug inhibits the generation of ROS by both activated and inactivated macrophages (the inhibition index with respect to placebo is on average about 50%) ( P <0.05).

7. AUTOPROTECTIVE PROPERTIES

Elixir with systematic administration increases the physical endurance and performance of animals.

The actoprotective properties of the dealcoholized elixir were evaluated in a modified Kiplinger test, recording the swimming speed of trained animals with repeated swimming of the standard distance. The dealcoholized elixir was administered orally daily, including the day of the test (1 hour before the swimming test) for 6 days in doses corresponding to 3, 10 and 30 ml / kg of the native preparation. Control animals were given a placebo over the same period.

It was found that the elixir has a significant stimulating effect on the physical performance of mice when administered at doses of 10 and 30 ml / kg, and at a dose of 3 ml / kg this effect is detected as a trend. The research results are presented in table. 16 in the form of relative indicators, expressed as a percentage of control. The stimulation of working capacity is manifested by an increase in starting power (up to 25%), a decrease in fatigue coefficient (by 16-23%) and a significant increase in the amount of work according to the criteria A ₅₀ (by 34-42%) and A ₁₀₀ (by 29-34%).

8. STRESS PROTECTIVE PROPERTIES

It has been established that the dealcoholized elixir with single and multiple administration to rats has stress-protective properties under conditions of intense stress exposure.

a) When evaluating the stress-protective activity of a dealcoholized elixir under conditions of a single injection, rigid fixation of rats on the back for 10 hours was used as an experimental model of intense stress. Elixir with a single oral administration 30 minutes before the experiment in doses corresponding to 3.10 and 30 ml / kg of the native drug, has a pronounced adaptogenic activity, which is expressed in a significant reduction in the number of stressful stomach ulcers in rats (table. 17).

b) The stress-protective activity of the dealcoholized elixir under conditions of repeated administration was evaluated using the same experimental model under conditions of tight 18-hour fixation of rats on the back. Elixir, after preliminary 5-day oral administration in doses corresponding to 3, 10 and 30 ml / kg of the native preparation, significantly weakens organ and endocrine stress phenomena, including thymo-lymphatic involution and ulcerative lesions of the gastric mucosa (Table 18).

9. IMMUNOSTIMULATING PROPERTIES

a) The effect of the elixir on humoral immunity

The property of the elixir to have a stimulating effect on humoral immunity has been established. It was shown that the dealcoholized elixir in experiments on CBA mice has immunostimulating activity according to tests for the production of hemagglutinins, generation of antibody-forming cells (AOKs) in the spleen and the mitogenic effect, which manifests itself in an increase in spleen cellularity in mice under conditions of antigenic stimulation (P <0.001-0.05).

The dealcoholized elixir, administered orally to CBA mice for 4 days after ram erythrocyte immunization with doses corresponding to 3, 10 and 30 ml / kg of the native preparation, increases the absolute and relative content of nuclear cells in the spleen by 53-72% (P <0, 05-0.01).

The ability of the drug, administered in the same doses at the same time, to increase the number of AOK cells in the spleen by 1.4-2.7 times (calculated per organ) (P <0.05-0.01), was established in comparison with the control.

b) The effect of the elixir on the reactions of T-cell immunity

The stimulating effect of the elixir on the reactions of T-cell immunity has been established.

It has been shown that the dealcoholized elixir, given 4-day oral administration at a dose corresponding to 10 ml / kg of the native preparation, stimulates a delayed-type hypersensitivity reaction (stimulation index 1.48; p <0.05). The moderately pronounced stimulating effect of dealcoholized elixir (with 6-day oral administration in doses equivalent to 3, 10 and 30 ml / kg of the native drug) on T-cell immunity on the model of the graft versus host (GVHD) reaction was established. A significant increase in the formation of GVHD in hybrid mice (CBA × C ₅₇ Bl ₆ ) F ₁ to lymphocytes of the parent phenotype (CBA) was noted. The reaction index was 1.39-1.83 in mice of the experimental group versus 1.19 in control animals (P <0.05).

c) The effect of elixir on phagocytosis

It has been established that the dealcoholized elixir has a stimulating effect on the phagocytic function of neutrophils in both in vitro experiments on human donor blood cells and in vivo experiments on mice.

The addition of dealcoholized elixir in a wide range of concentrations (0.3-30 ml / l) to human blood samples in vitro has a stimulating effect on the phagocytic activity of neutrophils. The average values of the phagocytosis stimulation index for the elixir are 1.18-1.28 (differences with the control are significant, p <0.05).

In in vivo experiments, a dealcoholized elixir administered orally to mice for 6 days at doses corresponding to 3, 10 and 30 ml / kg of the native preparation stimulates phagocytic activity in mice, increasing the proportion of phagocytic cells by 2.1-3.4 times ( differences with control are significant, p <0.05-0.01).

d) Corrective effect of an elixir in case of stress immunodeficiency

It has been established that the dealcoholized elixir has an immunocorrective effect under conditions of stressful immunosuppression.

The study of the immunocorrector activity of the elixir was carried out on a model of stressogenic immunodeficiency induced in mice by 2-fold swimming for 60 minutes, performed 30 minutes and 24 hours after immunization of animals with an intraperitoneal suboptimal dose of sheep erythrocytes. The immune response was evaluated by the number of antibody-forming cells (AOKs) in the spleen, which was determined by the Cunningham method on the 5th day after immunization. The dealcoholized elixir was administered daily for 4 days at a dose corresponding to 10 ml / kg of the native preparation. The experimental results are presented in table. 19.

The study of the corrective effect of the elixir in conditions of stressful immunodeficiency showed that the elixir at a dose of 10 ml / kg not only weakens the depression of the immune response, but also ensures its full recovery. The final immune response against the background of the use of the elixir under these conditions exceeded the response in the control (without stress) by 1.9 times and the response against stress exposure by 4.8 times.

e) Interferon-inducing activity of elixir (dealcoholized and native drug)

The study of the interferonogenic activity of the elixir in cell culture was carried out using a transplantable culture of human leukemia cells (L-41). The studies used the virus of vesicular stomatitis (BBC), a strain of Indiana.

It has been established that both native and dealcoholized elixir are highly active interferon inducers. The results of the study are presented in table. 20.

Thus, an elixir is a multivalent drug that combines pharmacological effects: neurotonizing, anti-alcohol, nootropic, antidiarrheal, the ability to weaken the manifestations of radiation sickness, antioxidant, actoprotective, stress-protective, immunostimulating. The components of the elixir do not show mutual antagonism and, on the contrary, provide the effect of complementarity or potentiation. Elixir is practically non-toxic to mammals. Doses of plant components included in the elixir do not exceed pharmacopoeial.

The elixir "Doctor Petrov" is taken orally by 15-45 ml (1-3 tablespoons) 1-2 times a day, in the morning after meals for 2-3 weeks.

The elixir "Doctor Petrov", obtained by the claimed composition of ingredients, is intended for use in adults as a therapeutic and prophylactic adaptogenic and restorative agent, with intensive and prolonged neuropsychic and physical exertion in order to quickly and fully restore working capacity, with asthenic manifestations of various origins , during convalescence after chronic diseases, in patients with initial manifestations of cerebrovascular insufficiency (decreased performance ty, fatigue, impaired memory and attention). The claimed elixir is also used for prophylactic purposes at the first signs of colds, during antibiotic therapy, radiation and chemotherapy and other conditions accompanied by a weakening of the immune system.

Based on the experimentally established properties of the elixir, it can also be used as a prescription component of alcoholic beverages, added to weaken the manifestations of the toxic effects of ethanol; as a means of weakening the manifestations of radiation damage; as an antidiarrheal agent; as an antioxidant; as a means of preventing negative manifestations of stress, including stress-induced erosive and ulcerative lesions of the stomach.

Sources of information

1. Patent RU No. 2045273, A 61 K 35/78. A composition with vitamin activity / E.D. Goldberg, A.M. Dygay, N.I. Suslov, A.I. Potapov. - No. 5045944/14; Claim 04/28/92; Publ. 10/10/1995. // Inventions. - 1995. - No. 28. - S.126.

2. Patent RU No. 2031930, MKI C 12 G 3/06. The composition of the ingredients for the balm “Crimean” / A.Ya. Yalanetsky, M.F. Mumakov, A.P. Polshchikov, A.A.Sycheva, N.N.Bakova. - No. 94013669/13; Claim 04/28/94; Publ. 03/27/1995. // Inventions. - 1995. - No. 9 - S.158.

3. Alekseev A.I. "The experimental and clinical-physiological justification for the use of the Crimean balm for rehabilitation at the Truskavets resort of victims of the Chernobyl disaster. // Abstract of dissertation for the degree of candidate of medical sciences. Lvov, 1994, S.4-5.

4. Patent RU No. 2018316, MKI A 61 K 35/78; A 23 L 2/00. Means possessing tonic and restorative effect “Energoton” / S.Ya. Sokolov, V.P. Boyko, M.N. Lyakina, G.N. Russian. - No. 5030773/14; Claim 03/04/92; Publ. 08/30/1994. // Inventions. - 1994. - No. 16. - p.22.

5. Patent of Ukraine, A 61 K 35/00, N 14602, Bull. 2,1997.

6. Patent RB No. 4041, MKI A 61 K 35/78, C 12 G 3/06. The composition of the ingredients for the preparation of “Tonus” balm / P.T. Petrov, V. M. Tsarenkov, M. V. Gavrilov, L. N. Dunets, L. N. Grinevich, A. I. Bondarenko; Declared 10.02.1998; Publ. 09/30/2001. Afitsyiny Bulletin / Jyarzh. US Pat. Departments Belarus - 2001. - No. 3 (30). - S. 96.

7. Patent RB No. 4042, MKI A 61 K 35/78, C 12 G 3/06. The composition of the ingredients for the preparation of medicinal fortified balm / P.T. Petrov, V.M. Tsarenkov, M.V. Gavrilov, L.N. Dunets, L.N. Grinevich, A.I. Bondarenko; Claim 02/10/1998; Publ. 09/30/2001. Afitsyiny Bulletin / Jyarzh. US Pat. witchcraft Belarus - 2001. - No. 3 (30). - S.96-97 (prototype).

8. The Register of Medicinal Products of Russia (RLS-2001). Encyclopedia of drugs. Ed. 8, rev. and add. / Ed. Yu.F. Krylova. M., 2001 .-- P.1032.

Claims (1)

The composition of the ingredients for the preparation of an elixir containing dry chokeberry fruits, aronia (rose ash), rosehips, linden flowers, bitter wormwood grass, chaga, black pepper, nutmeg, nettle leaves, prune fruits, propolis, aloe juice or dry aloe leaves, honey bee and ethyl alcohol 40%, characterized in that it additionally contains ginseng roots, purple coneflower grass, oregano grass, hawthorn fruit, incense rhizomes, St. John's wort grass, dried grapes and sugar color or sugar in the following ratios of ingredients ntov, g: Ginseng Roots 0.1-0.6 Echinacea purpurea herb 1.5-30.0 Propolis 0.25-2.5 Dry aloe tree leaves or 0.25-2.5 Aloe juice 15.0-150.0 Chaga 0.5-10.0 Rhizomes of incense 0.5-10.0 St. John's wort grass 0.5-10.0 Hawthorn fruits 0.5-10.0 Fruits of chokeberry (chokeberry) dry chokeberry 2.5-50.0 Rosehips 5.0-100.0 Linden flowers 1.0-20.0 Wormwood herb 0.025-0.5 Nettle leaves 1.0-20.0 Bee honey 2.5-50.0 Oregano herb 0.05-1.0 Dried grapes 2.0-40.0 Nutmeg 0.25-5.0 Prune fruits 5.0-100.0 Black pepper 0.05-1.0 Sugar or 150.0 Sugar color 225 Ethyl alcohol 40% Before receiving 1000 ml of elixir