RU2311193C1 - Agent possessing nootropic and adaptogenic activity - Google Patents

Abstract

FIELD: medicine, phytotherapy, pharmaceutical industry.

SUBSTANCE: invention relates to an agent possessing nootropic and adaptogenic activity and to using dropwort above-ground part extract (Filipendula ulmaria (L.) Maxim.) as an agent possessing nootropic and adaptogenic activity. Above described agent possesses the expressed nootropic and adaptogenic activity.

EFFECT: valuable medicinal properties of agent.

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Description

The invention relates to medicine, specifically to clinical pharmacology, and can be used for pharmacological correction of central nervous system diseases and relates to drugs with nootropic and adaptogenic activity obtained from plant materials.

Synthetic drugs used to treat these diseases have insufficient therapeutic efficacy, have a number of side effects that limit the possibility of their use, especially in the conditions of continuous work [1]. Herbal remedies can play a significant role in solving this problem. Closest to the proposed solution is the herbal medicine Ginsana (Pharmaton, Switzerland), which has nootropic and adaptogenic activity, which is obtained from the white ginseng root introduced in Switzerland [2], which does not have a raw material base in Russia.

A new technical task is to expand the arsenal of central nervous system protection products with nootropic and adaptogenic activity obtained from plant materials.

The problem is solved by using, as a nootropic and adaptogenic agent, an extract of the aerial part of the common meadowsweet (Filipendula ulmaria (L.) Maxim.).

In folk medicine, the plant is used as an anti-inflammatory, astringent, wound healing and tonic agent [3]. Experimental studies of recent years have revealed that extracts of meadowsweet have reduced capillary permeability, exhibit pronounced anticoagulant, antiulcer, antidiabetic and anticarcinogenic effects [4, 5]. The flowers of the meadowsweet are currently approved for use in official medicine in the form of decoctions and hot infusions as anti-inflammatory, astringent and wound healing agents [3, 6]. In the literature there is no data on the use of the extract of the aerial part of the meadowsweet (Filipendula ulmaria (L.) Maxim.) As an agent with nootropic and adaptogenic activity.

Distinctive features showed new properties in the claimed combination - it was first established that as a nootropic and adaptogenic agent, an extract from the aerial part of the meadowsweet (Filipendula ulmaria (L.) Maxim.) Was used.

In view of the above, the claimed solution should be considered as meeting the criterion of “significant differences”.

The use of the extract of the aerial part of the meadowsweet for the proposed purpose was made possible by identifying experimentally its new properties, namely the ability to normalize the central nervous system due to nootropic and adaptogenic activity.

As experimental studies show, the extract of meadowsweet has more pronounced nootropic and adaptogenic activity compared to the reference drug "Ginsana", which will lead to a higher effect in clinical practice.

A new property was discovered as a result of an experimental study of the nootropic and adaptogenic activity of water and water-ethanol extracts (40, 70, 95%) of common meadowsweet.

Pharmacological studies were performed on white outbred male mice 20-22 g. All animals of the 1st category (conventional linear mice) were obtained from the collection fund of the laboratory for experimental biological modeling of the Research Institute of Pharmacology of the Tomsk Scientific Center SB RAMS. The experiments were carried out in the autumn-winter period. Work in the framework of experimental methods was carried out from 10 a.m. and finished by 15 p.m. Animals were kept in a vivarium on a normal feeding ration with free access to water and food (except for cases where other conditions are specified). Killing animals was carried out by an overdose of ether anesthesia.

The pharmacological effects of corybum extracts were evaluated by their effect on learning and memory when developing and reproducing the conditioned passive avoidance reflex (passive avoidance reaction), tentative research behavior in the “open field”, resistance to hypoxic effects and physical performance and adaptation to physical activity.

Approximate research behavior was studied under the conditions of the “open field” model, which is one of the most commonly used teaching methods used to judge the functional state of the central nervous system [7, 8]. The “open field” experimental setup is a 40 × 40 × 20 cm camera with a square floor and white walls. Its floor, divided into 16 squares, has in each of them a circular hole with a diameter of 3 cm. From above, the camera is illuminated by an electric incandescent lamp with a power of 100 W, located at a height of 1 m from the floor. The mouse is placed in one of the corners of the camera and within 2 minutes the number of movements from square to square (horizontal activity), the number of stands on the hind legs (vertical activity), the number of hole examinations (mink reflex), the number of washings (grooming) and the number of acts are recorded defecation by the number of fecal balls (boluses), calculate the coefficient of asymmetry of behavior in the form of the ratio of the number of horizontal movements to the total motor activity, expressed as a percentage.

Hypoxic trauma was studied under conditions of hermetic hypoxia. For a more detailed assessment of the effect of hypoxic injury in mice, we studied not only survival under conditions of hypoxia, but also evaluated the functional state of the central nervous system by the state of tentative research behavior and memory by reproducing passive avoidance reaction, which is produced immediately before hypoxic exposure, as described below. Hermetic volume hypoxia was modeled by placing mice previously selected by weight (g) in a 500 ml hermetically sealed chamber. The mice were kept until a convulsive seizure occurred, after which the animals were removed from the chamber, allowed to sit for 1 h and then they studied the tentative-research behavior in the “open field”. The technique of the conditioned reflex of passive avoidance [7, 9] is based on the suppression of the innate reflex of preference for dark space in rodents. The experimental setup is a camera consisting of two compartments - large (light) and small (dark). The animal is placed in the light compartment and after a while it goes into the dark one, after which the hole connecting the two compartments is closed with a door and the electric current is supplied by pulses of 50 ms duration with a frequency of 5 Hz and amplitude to the floor of the dark compartment, which is a lattice of parallel alternating electrodes 50 mA After 10 seconds, the door is opened and the animal can jump out into the bright compartment with the usual floor. As a result of the described procedure, a conditioned reflex of avoiding dark space was developed in animals. When checking the reflex, the animal was placed in the corner of the chamber of the bright compartment, opposite from the entrance, and was observed for 3 min. The time of the first entry into the dark compartment (latent time of entry), the total time spent in the dark compartment, and the number of animals with a developed reflex were recorded. The criterion for the presence of a reflex was considered the absence of an animal entering the dark compartment for 3 min from the moment the mouse was placed in a bright chamber. Checking the safety of the reflex was carried out after 24 and 48 hours, 1, 2 and 3 weeks after hypoxic exposure.

The effect on physical performance and adaptation to physical activity was studied under the conditions of the forced swimming technique with a heavy load - 10% of the mouse body weight [10] at a water temperature of 28 ° C. The animals swam to fatigue twice with an interval of 1 hour. The performance was judged by the total duration of swimming of the animals, the effect - by differences with the control group.

Extracts from the aboveground part of the common meadowsweet and comparison preparations were administered in an animal course daily for five days once through a probe into the stomach in the form of a solution or suspension in purified water 1 hour before testing. The dose of extracts was 50 mg / kg. Piracetam (Nootropil, Chieh-Polfa Group) at a dose of 400 mg / kg and white ginseng root extract (Ginsana, Pharmaton, Switzerland) at a dose of 100 mg / kg were used as reference preparations for reference nootropic activity. Animals of the control pathology and intact groups received an equivalent amount of purified water.

The obtained experimental data were processed statistically. The significance of the differences was judged by testing the probability of the null hypothesis using t student test and Wilcoxon criterion. When analyzing data on the reproduction of the reflex (the proportion of animals with a preserved reflex,%), the Fisher method was used to compare the fractions. The differences were considered significant at p≤0.05 [11, 12].

The course introduction of meadowsweet extracts on 70 and 95% ethanol improves locomotor activity in the “open field” upon registration 30 minutes after hypoxic exposure (Table 1). The extract by 70% ethanol reduces the latent time of entry into the dark compartment during the development of the reflex, bringing this indicator as close as possible to the values of intact control. Extracts of meadowsweet improve the safety of the conditioned reflex of passive avoidance and restore the reproducibility of the reflex from 50 to 90% when tested 24 hours, 7, 14 and 21 days after hypoxic exposure. The most pronounced protective effect on the functions of the central nervous system during hypoxia of the hermetic volume is exerted by the plant extract obtained on 70% ethanol.

In all groups of animals treated with meadowsweet extracts, starting from the first day of the experiment, an increase in swimming duration was observed in comparison with the control (Table 2). The increase in performance under the influence of extracts was maximally manifested on the fourth day of the experiment. The most pronounced and lasting adaptogenic effect under the conditions of the forced swimming technique was observed in animals treated with meadowsweet extract on 70% ethanol.

Thus, when studying the effect of extracts from the aerial part of the volcanic meadowsweet on some pathological conditions of experimental animals, it was found that all the studied extracts exhibit pronounced nootropic activity, positively affect physical performance and adaptation to physical activity. The highest activity at a dose of 50 mg / kg is from meadowsweet extract on 70% ethanol, the effect of which is superior to nootropic (preservation of orientational research behavior in the open field and conditioned reflex of passive avoidance after hypoxic injury) and adaptogenic (working capacity and adaptation to physical activity) activity the reference preparation is Ginsana and corresponds with a slight advantage to the effect of piracetam.

Experimental studies have shown that the extract of meadowsweet on 70% ethanol has a nootropic and adaptogenic effect and is superior to other standard nootropics, because shows great activity. Extraction of 70% ethanol of the aerial part of the plant increases the nootropic and adaptogenic effects of the target product due to the most complete extraction of biologically active substances (flavonoids, phenolcarboxylic acids, coumarins).

Based on the conducted experimental studies, it can be concluded that the use of the herb meadowsweet extract is promising for a higher therapeutic effect.

A positive effect was achieved due to the use of the extract of the aerial part of the meadowsweet herb (Filipendula ulmaria (L.) Maxim.) As a nootropic and adaptogenic agent, which allowed us to expand the arsenal of herbal remedies with nootropic and adaptogenic activity with an increased specific effect.

, n=10)Table 1
The effect of extracts from the aerial part of the meadowsweet on tentative-research behavior in the "open field", the development and preservation of the conditioned reflex of passive avoidance in mice after hypoxic exposure (

, n = 10) Observation groups Total motor activity after 30 min Latent time of entry into the dark compartment during reflex development, sec The proportion of animals with a preserved reflex during testing,% 24 hours after production 7 days after development 14 days after production 21 days after production Intact control 36.7 ± 3.6 * p≤0.01 29.5 ± 2.9 * p≤0.001 100 * p≤0.05 100 * p≤0.05 90 * p≤0.05 70 * p≤0.05 Hypoxic control 15.2 ± 4.2 77.1 ± 18.9 0 10 10 10 Water extract 17.9 ± 3.4 72.1 ± 15.3 70 * p≤0.05 70 * p≤0.05 70 * p≤0.05 70 * p≤0.05 40% ethanol extract 19.3 ± 4.6 71.8 ± 15.9 70 * p≤0.05 60 60 fifty 70% ethanol extract 26.8 ± 2.7 * p≤0.05 54.3 ± 12.9 90 * p≤0.05 90 * p≤0.05 80 * p≤0.05 80 * p≤0.05 95% ethanol extract 25.7 ± 2.0 * p≤0.05 73.5 ± 17.9 80 * p≤0.05 80 * p≤0.05 70 * p≤0.05 70 * p≤0.05 Ginsana 26.0 ± 2.0 * p≤0.05 64.3 ± 12.2 80 * p≤0.05 70 * p≤0.05 70 * p≤0.05 60 Piracetam 25.5 ± 1.7 * p≤0.05 56.0 ± 11.9 100 * p≤0.05 90 * p≤0.05 90 * p≤0.05 80 * p≤0.05 Note: * - differences are significant in relation to hypoxic control.

, n=10)table 2
The effect of extracts from the aerial part of the meadowsweet on the physical performance and adaptation of mice to physical activity (

, n = 10) Observation groups Duration of swimming, sec 1 day 2 day 3 day 4 day 5 day Intact control 102.7 ± 7.7 104.4 ± 7.1 93.1 ± 8.8 122.9 ± 9.9 119.3 ± 6.9 Water extract 106.3 ± 8.4 98.1 ± 7.3 86.9 ± 5.5 130.0 ± 9.3 127.6 ± 6.7 40% ethanol extract 101.8 ± 6.9 139.6 ± 16.1
* p≤0.05 95.4 ± 8.6 129.3 ± 6.6 113.0 ± 6.8 70% ethanol extract 111.8 ± 9.4 125.0 ± 8.4
* p≤0.05 107.3 ± 8.2 165.8 ± 13.6 * p≤0.02 144.1 ± 14.7 95% ethanol extract 137.0 ± 16.9 128.1 ± 7.8
* p≤0.02 105 ± 6.1 123.2 ± 6.5 124.4 ± 6.4 Ginsana 128.8 ± 11.6 124.0 ± 7.6
* p≤0.05 108.2 ± 8.5 169.8 ± 15.2 * p≤0.02 123.2 ± 6.7 Piracetam 103.8 ± 6.7 119.6 ± 6.1
* p≤0.05 95.2 ± 8.8 133.3 ± 7.0 120.0 ± 6.8 Note: * - differences are significant with respect to intact control.

Information sources

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Claims (1)

The use of the extract of the aerial part of the meadowsweet (Filipendula ulmaria (L.) Maxim.) As a means of having nootropic and adaptogenic activity.