RU2438677C1 - Psychostimulant agent - Google Patents

Abstract

FIELD: medicine, pharmaceutics. ^ SUBSTANCE: invention refers to medicine, more specifically clinical pharmacology, and can be used for pharmacological correction of the CNS diseases, and concerns drugs exhibiting psychostimulant action and prepared of inorganic (mineral) raw materials. The agent exhibits psychostimulant action, contains magnesium sulphate, ferric (II) sulphate, copper (II) sulphate and chrome (III) chloride. ^ EFFECT: psychostimulant agent extends the range of products exhibiting psychostimulant action, with high specific action. ^ 5 ex, 3 tbl

Description

The invention relates to medicine, specifically to clinical pharmacology, can be used for pharmacological correction of central nervous system diseases and relates to drugs with a psychostimulating effect obtained from inorganic (mineral) raw materials.

Synthetic drugs currently used to treat these diseases have insufficient therapeutic efficacy and have a number of side effects (disorders of the central nervous system, including insomnia, irritability, anxiety, tachycardia, headache, tremor, agitation, confusion , paranoid psychosis, angina attacks, as well as the development of drug dependence), limiting the possibility of their use, especially in the context of ongoing work [1, 2]. Means based on inorganic (mineral) raw materials can play a significant role in solving this problem.

An adequate prototype was not found in the literature.

The objective of the invention is to expand the arsenal of central nervous system protection products with a psychostimulating effect obtained from inorganic (mineral) raw materials.

The problem is solved by using as a means with a psychostimulating effect, the composition in the following ratio, wt.%: Magnesium sulfate 77.76835-50.22505, iron (II) sulfate 13.73-30.27, copper (II) sulfate 8 , 50-19.50 and chromium (III) chloride 0.00165-0.00495.

It is new that for the first time as a tool with a psychostimulating effect, they use a composition containing magnesium sulfate, iron (II) sulfate, copper (II) sulfate and chromium (III) chloride.

In medicine, magnesium sulfate is used as a sedative, anticonvulsant, antispasmodic and laxative (in large doses), iron (II) sulfate - in the complex treatment of hypochromic (iron deficiency) anemia, copper (II) sulfate - antiseptic, astringent and cauterizing (externally ) and chromium (III) chloride are not used, although other salts (chromium picolinate and asparaginate) are part of biologically active food supplements and vitamin-mineral complexes to enhance the lipolytic activity of blood serum [3]. There are no data in the literature on the use of magnesium sulfate, iron (II) sulfate, copper (II) sulfate and chromium (III) chloride as a means with a psychostimulating effect.

The ingredients and their ratio are selected experimentally. The use of magnesium sulfate, iron (II) sulfate, copper (II) sulfate and chromium (III) chloride for the proposed purpose was made possible by identifying experimentally its new properties, namely the ability to normalize the functions of the central nervous system due to the psychostimulating effect.

A new property was discovered as a result of an experimental study of the psychostimulating effect of a composition containing magnesium sulfate 77.76835-50.22505, iron (II) sulfate 13.73-30.27, copper (II) sulfate 8.50-19.50 and chromium (III) chloride 0.00165-0.00495.

Distinctive features showed in the inventive combination of new properties that are not explicitly derived from the prior art in this field and are not obvious to a specialist. For the first time it was established that as a means of having a psychostimulating effect, one can use the following composition containing magnesium sulfate, iron (II) sulfate, copper (II) sulfate and chromium (III) chloride.

An identical set of features was not found in the patent and medical literature.

The proposed tool can be successfully used in practical health care for the correction of diseases of the central nervous system.

Based on the foregoing, the present invention should be considered relevant to the conditions of patentability "Novelty", "Inventive step", "Industrial applicability".

The invention will be clear from the following description.

Example 1. Take exact weighed ingredients in the following ratio, wt.%:

magnesium sulfate 77.76835, iron (II) sulfate 13.73, copper (II) sulfate 8.50 and chromium (III) chloride 0.00165, crushed in a porcelain mortar and thoroughly mixed until a homogeneous granular mass (C1).

Example 2. Take accurate weighed ingredients in the following ratio, wt.%:

magnesium sulfate 63.9967, iron (II) sulfate 22.00, copper (II) sulfate 14.00 and chromium (III) chloride 0.0033, ground in a porcelain mortar and thoroughly mixed until a homogeneous granular mass (C2) is obtained.

Example 3. Take accurate weighed ingredients in the following ratio, wt.%:

magnesium sulfate 50.22505, iron (II) sulfate 30.27, copper (II) sulfate 19.50 and chromium (III) chloride 0.00495, ground in a porcelain mortar and thoroughly mixed until a homogeneous granular mass (C3) is obtained.

Pharmacological studies were performed on outbred male mice weighing 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 Institution RAMS Scientific Research Institute of Pharmacology 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. Killing animals was carried out by an overdose of ether anesthesia.

The pharmacological effects of an agent containing magnesium sulfate, iron (II) sulfate, copper (II) sulfate and chromium (III) chloride were evaluated by the effect on the functional state of the central nervous system (tentative research behavior) on the open field model [4, 5] , for learning and memory in the development and reproduction of the conditioned reflex of passive avoidance (passive avoidance reaction) [6].

The proposed tool and the comparison drug was administered in an animal course daily for five days once through a tube into the stomach in the form of a solution or suspension in purified water 1 hour before testing. The proposed tool was administered at doses of 0.96, 3.84, 19.2 and 76.8 mg / kg. Intact animals 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 [7].

Example 4. Approximate research behavior was studied under the conditions of the “open field” model, which is one of the most commonly used methodological methods used to judge the functional state of the central nervous system [4, 5]. 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.

The course introduction of the proposed tool containing magnesium sulfate, iron (II) sulfate, copper (II) sulfate and chromium (III) chloride increases motor activity in the "open field" in normal animals (table 1, 2). When registering tentative research behavior in the first minute of the experiment, a tendency to increase activity manifests itself mainly in doses of 3.84, 19.2 and 76.8 mg / kg In the next two minutes, there is a stimulation of motor activity in all studied doses, and in the case of applying a dose of 19.2 mg / kg mainly due to an increase in horizontal movements and uprights, and when using a dose of 3.84 mg / kg due to the activation of a mink reflex, which indicates an increase in research activity.

Example 5. The effect on learning and memory was investigated during the development and reproduction of the conditioned reflex of passive avoidance (passive avoidance reaction). The passive avoidance reaction [6] 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 an electric current is supplied with pulses of 50 ms duration, 5 Hz frequency, to the floor of the dark compartment, which is a grid of parallel alternating electrodes amplitude of 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 minutes from the moment the mouse was placed in a bright chamber. Checking the safety of the reflex was carried out 24 and 48 hours, 1, 2 and 3 weeks after the development of the reflex.

The proposed tool in all doses increases the safety of the conditioned reflex of passive avoidance and contributes to the reproducibility of the reflex from 67 to 100% when tested 24 hours, 7, 14 and 21 days after development (table 3). The most pronounced effect on learning and memory is exerted by doses of 3.84 and 19.2 mg / kg of the test drug.

Thus, when studying the effect of an agent containing magnesium sulfate, iron (II) sulfate, copper (II) sulfate and chromium (III) chloride, on some indicators of the state of the central nervous system of experimental animals, it was found that all studied doses exhibit pronounced psychostimulating properties. The greatest activity (increase in motor activity, the preservation of the conditioned reflex of passive avoidance) has the proposed tool in doses of 3.84 and 19.2 mg / kg

Based on the conducted experimental studies, it can be concluded that the use of an agent containing magnesium sulfate, iron (II) sulfate, copper (II) sulfate and chromium (III) chloride is promising for a higher therapeutic effect.

As experimental studies show, a tool containing magnesium sulfate, iron (II) sulfate, copper (II) sulfate and chromium (III) chloride has a pronounced psychostimulating effect, which will lead to a higher effect in clinical practice.

A positive effect was achieved through the use of a composition containing magnesium sulfate, iron (II) sulfate, copper (II) sulfate and chromium (III) chloride as a psychostimulating agent, which allowed to expand the arsenal of drugs with a psychostimulating effect, with an increased specific effect.

table 2

The effect of a tool containing magnesium sulfate, iron (II) sulfate, copper (II) sulfate and chromium (III) chloride on the indicators of orientational research behavior in the "open field" in normal mice in the next two minutes of the experiment

Observation group, dose Total motor activity Horizontal activity Vertical activity Mink reflex Sniffing Grooming Defecation Intact control 33.50 ± 9.75 14.67 ± 4.33 1.67 ± 0.67 3.67 ± 1.76 12.33 ± 3.35 0.67 ± 0.33 0.5 ± 0.34 C1, 0.96 mg / kg 44.33 ± 6.64 22.67 ± 5.01 0.67 ± 0.49 7.17 ± 2.48 12.33 ± 1.99 0.17 ± 0.17 1.33 ± 0.49 C1 3.84 mg / kg 62.33 ± 8.57 * 26.83 ± 5.71 2.17 ± 1.40 14.83 ± 3.23 * 18.00 ± 2.29 0,0 ± 0,0 0.50 ± 0.22 C1, 19.2 mg / kg 59.50 ± 4.46 * 28.00 ± 3.12 * 5.50 ± 1.52 * 13.00 ± 2.16 * 12.00 ± 2.05 0.50 ± 0.50 0.50 ± 0.34 C1, 76.8 mg / kg 40.40 ± 7.31 18.40 ± 4.55 2.60 ± 0.87 5.60 ± 2.73 13.40 ± 5.18 0.20 ± 0.20 0.20 ± 0.20 C2, 0.96 mg / kg 44.35 ± 6.65 22.70 ± 5.00 0.70 ± 0.50 7.21 ± 2.46 12.34 ± 2.00 0.17 ± 0.18 1.33 ± 0.47 C2, 3.84 mg / kg 62.37 ± 8.55 * 26.87 ± 5.74 2.20 ± 1.39 14.84 ± 3.21 * 17.94 ± 2.27 0,0 ± 0,0 0.49 ± 0.21 C2, 19.2 mg / kg 59.52 ± 4.46 * 28.02 ± 3.10 * 5.51 ± 1.51 * 13.01 ± 2.15 * 12.05 ± 2.03 0.52 ± 0.48 0.52 ± 0.30 C2, 76.8 mg / kg 40.39 ± 7.30 18.38 ± 4.50 2.58 ± 0.77 5.58 ± 2.76 13.41 ± 5.20 0.19 ± 0.19 0.19 ± 0.19 C3, 0.96 mg / kg 44.28 ± 6.61 22.69 ± 5.06 0.66 ± 0.50 7.20 ± 2.50 12.34 ± 1.95 0.16 ± 0.17 1.32 ± 0.48 C3, 3.84 mg / kg 62.40 ± 8.60 * 26.85 ± 5.75 2.21 ± 1.42 14.85 ± 3.25 * 18.05 ± 2.24 0,0 ± 0,0 0.51 ± 0.21 C3, 19.2 mg / kg 59.53 ± 4.48 * 28.03 ± 3.15 * 5.57 ± 1.57 * 13.04 ± 2.18 * 12.0b ± 2.08 0.54 ± 0.54 0.52 ± 0.32 C3, 76.8 mg / kg 40.41 ± 7.31 18.41 ± 4.54 2.58 ± 0.85 5.62 ± 2.71 13.36 ± 5.20 0.21 ± 0.19 0.21 ± 0.19 Note: * - differences are significant with respect to intact control; the significance of differences was evaluated at p≤0.05

Table 3

The effect of magnesium sulfate, iron (II) sulfate, copper (II) sulfate and chromium (III) chloride on the safety of the conditioned passive avoidance reflex in normal mice

Observation groups, dose 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 67 33 fifty 33 C1, 0.96 mg / kg one hundred 83 * p≤0.05 67 67 C1 3.84 mg / kg one hundred 100 * p≤0.05 83 83 * p≤0.05 C1, 19.2 mg / kg 83 100 * p≤0.05 one hundred 100 * p≤0.05 C1, 76.8 mg / kg 80 80 * p≤0.05 0 0 C2, 0.96 mg / kg one hundred 80 * p≤0.05 60 60 C2, 3.84 mg / kg one hundred 100 * p≤0.05 80 80 * p≤0.05 C2, 19.2 mg / kg 83 100 * p≤0.05 one hundred 100 * p≤0.05 C2, 76.8 mg / kg 80 80 * p≤0.05 0 0 C3, 0.96 mg / kg one hundred 80 * p≤0.05 70 60 C3, 3.84 mg / kg one hundred 100 * p≤0.05 80 80 * p≤0.05 C3, 19.2 mg / kg 80 100 * p≤0.05 one hundred 100 * p≤0.05 C3, 76.8 mg / kg 80 80 * p≤0.05 0 0 Note: * - differences are significant with respect to intact control; the significance of differences was evaluated at p≤0.05

Literature

1. Mashkovsky M.D. Medicines - M.: New Wave, 2002. - T. 1. - S.142-150.

2. Malin D.I. Side effect of psychotropic drugs. - M.: University Book, 2000. - S.190-193.

3. Skalny A.V. Chemical elements in the physiology and ecology of man. - M.: ONIX 21st Century Mir, 2004 .-- S.99-136.

4. Walsh R.N., Cummins R.A. The open - field test: a critical review // Psychol. Bull. - 1976. - V.83. - P. 482-504.

5. Suslov N.I. Pathogenetic substantiation of the psychopharmacological effects of drugs of natural origin (experimental study): Diss. Doct. honey. sciences. - Tomsk, 1995 .-- P.81-82.

6. Buresh Ya., Bureshova O., Houston J.P. Methods and basic experiments on the study of the brain and behavior. - M .: Higher school, 1991 .-- 175-177.

7. Belenky M.L. Elements of a quantitative assessment of the pharmacological effect. - L .: Medicine, 1963. - P.81-147.

Claims (1)

Psychostimulant, characterized in that it contains a composition consisting of magnesium sulfate, iron (II) sulfate, copper (II) sulfate and chromium (III) chloride in the following ratio, wt.%:
magnesium sulfate 50.22505-77.76835 iron (II) sulfate 13.73-30.27 copper (II) sulfate 8.50-19.50 chromium (III) chloride 0.00165-0.00495