RU2361599C1 - Pharmaceutical composition possessing sedative and anxyolitic action - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention concerns a pharmaceutical industry, in particular, a composition possessing sedative and anxiolytic action. A pharmaceutical composition possessing sedative and anxiolytic action, containing motherwort extract, at least one pharmaceutically comprehensible compound of magnesium, vitamin B₆ and auxiliary substances taken in certain parity.

EFFECT: reception of a composition which possesses increased sedative and anxiolytic action, and does not cause drowsiness.

3 cl, 3 tbl

Description

The invention relates to the pharmaceutical industry and medicine, namely to sedatives of plant origin, and can be used to treat functional disorders of the central and autonomic nervous system.

The changed lifestyle and nutritional nature of modern man have led to the widespread dissemination of various types of borderline anxiety disorders, manifested in mental, behavioral and somatic disorders. Often people complain of causeless headaches, increased fatigue, fears, anxiety, nervousness, impatience, insomnia, a constant feeling of fatigue, uncontrolled irritation, from which both the person himself and the people around him suffer. Usually, doctors recommend removing such symptoms with herbal sedatives based on valerian root, motherwort and other medicinal plants.

Motherwort as a sedative is used in the form of infusion, tincture, extract (Mashkovsky M.D. Medicines. - 15th ed. Revised., Revised and supplemented. - M.: RIA "New Wave", 2007, p. 88 ) Motherwort is also part of numerous collections and complex preparations of sedative action (RF patents No. 2019185, No. 2223778, No. 2278684, No. 2281111, No. 2295968, No. 2298413).

Known tablets based on motherwort extract for the treatment of functional disorders of the central nervous system according to the patent of the Russian Federation No. 2207116, containing dry motherwort extract 7-14 wt.% And excipients.

More recently, it was found that the cause of many disorders of the central and autonomic nervous system is magnesium deficiency, therefore, it is recommended to use magnesium preparations for these disorders.

Preparations containing magnesium are traditionally used in medical practice for various purposes. Magnesium carbonate is used as an antacid and laxative, as well as to replenish magnesium deficiency (MD Mashkovsky. Medicines. - 15th ed. Revised., Rev. And add. - M .: RIA "New Wave", 2007) . There are well-known magnesium preparations of foreign companies designed to fill the deficiency of magnesium Magne B6 (magnesium lactate dihydrate plus vitamin B6), Magnnerot (magnesium orotate), Magnesium plus (magnesium carbonate and magnesium lactate plus B vitamins) (Vidal Handbook, 2006).

The disadvantages of the known preparations of magnesium is not a wide range of sedative effects.

The solution closest to the invention is motherwort tablets "Leonirid" for the treatment of functional disorders of the central nervous system according to the RF patent No. 2145230, containing on a tablet weighing 0.3 g of 4.2-42 wt.% Motherwort extract in terms of dry matter and excipients.

The disadvantage of the prototype is not a wide spectrum of action, since it contains only motherwort, in addition, motherwort in large doses (42 wt.%) Can cause symptoms of central nervous system depression, i.e. drowsiness.

The objective of the invention is the creation of a new sedative drug with an extended spectrum of action that does not cause depression of the central nervous system.

The technical result is the fulfillment of the stated purpose, namely the expansion of the spectrum of action due to the combination of sedative and mild anxiolytic (anti-anxiety) action without drowsiness.

The specified result is achieved by the fact that the pharmaceutical composition contains motherwort extract, magnesium compound, vitamin B6 and excipients, in the following ratio of components, wt.%:

motherwort extract 2.8-10 magnesium compound 20-50 vitamin b6 0.1-1 Excipients up to 100

The magnesium compound included in the composition is selected from the group carbonate, sulfate, lactate, orotate or magnesium citrate, since it is these compounds that are pharmaceutically acceptable for drugs. Made pharmaceutical composition in the form of tablets, capsules or sachets.

Five-lobed motherwort (Leonurus quinquelobatus) and the motherwort (cardiac) of the Labiate family (Labitae) used along with it is one of the widely known medicinal plants approved for medical use in Russia. The grass of these species of motherwort has been introduced into the Gosfarmakopeia of the Russian Federation as a plant raw material.

Motherwort grass contains sugars, alkaloids, flavonoid glycosides (rutin, quinqueloside, cosmen, hyperoside, quercetrin, etc.), tannins, saponins, iridoids. The chemical composition of the plant is currently being studied.

Motherwort has a sedative, cardiotonic, hypotensive effect, has a restorative effect.

Vitamin B6 takes an active part in the processes of fat and carbohydrate metabolism, it is necessary for the normal functioning of the central and peripheral nervous system.

Magnesium is a physiological regulator of the excitability of a cell and is necessary for the normal functioning of depolarization processes; with a lack of magnesium, the cell becomes over-excitable. Magnesium has an inhibitory effect on the conduction of a nerve impulse and is a natural insulating material in its path.

The applicant found that motherwort extract combines well with magnesium preparations and vitamin B6 and gives good results in the treatment of anxiety disorders without central nervous system depression. The claimed pharmaceutical composition exhibits not only a sedative effect, but also a mild anxiolytic effect, while not causing muscle relaxation and sleeping pills. As a result of tests conducted on volunteers, it was recommended to use the composition as a daily sedative, which regulates the functional state of the nervous system, relieves stress and emotional overstrain.

Sedatives, including motherwort extract, magnesium carbonate and vitamin B6, from the prior art is not identified, therefore, the technical solution meets the criterion of "novelty."

The combination in the same composition of motherwort extract, vitamin B6 and magnesium compounds in the stated proportions made it possible to achieve a super-total effect, since the composition of the drug is balanced in such a way that it contains three active components in a ratio optimal for assimilation by the body. The body’s absorption of magnesium in the presence of motherwort and vitamin B6 extract is significantly higher than in the known preparations, respectively, the sedative effect of motherwort is potentiated and supplemented by the sedative effect of magnesium, since their effect on the central nervous system is carried out in different ways. Magnesium is involved in the regulation of transmission of nerve impulses, provides support for a variety of energy and plastic processes in the nervous tissue, and motherwort has a sedative, hypotensive and cardiotonic effect (it slows down the heart rhythm, increases the strength of heart contractions). Vitamin Bb delivers magnesium inside the cell. As a result, the effect of the claimed combined preparation is realized mainly in the form of a combination of sedative and anxiolytic (anti-anxiety) effects, that is, the claimed technical result is fulfilled.

In more detail, the claimed pharmaceutical composition is described using non-limiting examples of its implementation in the form of oral medicines, which are shown in table 1.

Table 1 Name of ingredients Compositions, g 0.5 g tablets Capsules weighing 0.3 g 0.5 g tablets 1.0 g tablets Motherwort extract 0.014 0,03 0.05 0.05 Vitamin B6 0,0005 0.001 0,0005 0.005 Magnesium compound (magnesium carbonate or magnesium sulfate, or magnesium orotate, or magnesium lactate, or magnesium citrate) 0,1225 0.15 0,1225 0.5 Excipients MCC or starch 0.353 0.115 0.317 0.425 Calcium Stearate or Magnesium Stearate 0.005 0.002 0.005 0.01 Aerosil 0.005 0.002 0.005 0.01

These funds are obtained by mechanical mixing of the ingredients, followed by tableting or filling capsules or sachets using known equipment. As a magnesium compound in the composition, magnesium carbonate or magnesium sulfate, or magnesium orotate, or magnesium lactate, or magnesium citrate, which have similar pharmacological effects (the Russian Medicines Register of the Radar. Drug Encyclopedia. - 15th issue / Ch. Edited by G.L. Vyshkovsky. - M.: “Radar-2007”, 2006).

Physico-chemical characteristics of the pharmaceutical composition: tablets and capsules or sachets from gray to beige in color with a splash, specific smell, bitter taste. The content of active substances per tablet, capsule, sachet: iridoids not less than 0.25 mg, magnesium not less than 25 mg, vitamin B6 not less than 0.5 mg.

Clinical trials of the proposed composition in the form of tablets were conducted on the basis of the State Educational Institution “Consultative and Diagnostic Center” in Biysk.

The study was conducted by direct clinical examination of patients with observation for one month and assessment of the dynamics of autonomic disorders, as well as the quality of life indicator was studied in patients, as a test integrating the patient’s physical, mental, emotional and social characteristics. The results were entered in the form of a standard protocol at the beginning of treatment, after 15 days, at the end of the observation (after 30 days).

A total of 60 specially selected patients with vegetative-vascular dystonia were under observation. As they were treated by random sampling (first-second), the patients were divided into two groups: the main group - 30 people who received 30 tablets for 30 days with meals 2 times a day and a control group (30 people) who having vegetovascular dystonia (VVD), in the complex therapy of the claimed composition was not received.

The results are shown in tables 2, 3.

table 2 Dynamics of the main indicators of the psycho-vegetative syndrome in the main and control groups of the IRR (in points ± m) No. p / p Main characteristics The main group n = 30 Control group n = 30 To the beginning Finally To the beginning Finally one 2 3 four 5 6 one General cerebral: - headache 3.2 ± 0.3 1.0 ± 0.9 2.8 ± 1.2 2.0 ± 0.8 - dizziness 2.3 ± 0.8 0.6 ± 0.6 2.0 ± 1.0 1.5 ± 0.6 - noise in the head 1.6 ± 0.4 0.4 ± 0.1 1.8 ± 0.4 1.2 ± 0.2 2 Sleep disturbance 4.0 ± 0.4 0.4 ± 0.4 3.0 ± 0.4 2.0 ± 0.8 3 Memory impairment 3.2 ± 0.8 1.0 ± 0.6 2.8 ± 1.2 2.0 ± 0.8 four Fatigue (asthenic disorders) 3.6 ± 1.0 0.2 ± 0.4 2.7 ± 0.3 2.2 ± 0.8 5 Emotional disturbances: - emotional lability 3.6 ± 1.0 0.3 ± 0.7 3.0 ± 1.0 2.3 ± 0.7 - irritability 3.0 ± 0.0 0.2 ± 0.8 3.0 ± 0.5 2.0 ± 0.8 - anxiety 3.0 ± 0.0 0.5 ± 0.2 3.0 ± 0.0 1.5 ± 0.5 - decrease in motivation 2.3 ± 0.1 0.3 ± 0.2 2.0 ± 1.0 1.4 ± 0.4 - decrease in mood background, hypochondria 4.0 ± 0.0 0.7 ± 0.5 4.0 ± 0.0 2.5 ± 0.7 - contact 1.8 ± 0.2 0.2 ± 0.0 1.5 ± 0.3 1.2 ± 0.1 Note: 4 points - pronounced; 3 points - expressed; 2 points - moderately expressed; 1 point - poorly expressed; 0 points - no symptom. Table 3 Dynamics of vegetative disorders at the beginning and end of observation No. p / p Main characteristics The main group n = 30 Control group n = 30 At the beginning of observation At the end of observation At the beginning of observation At the end of observation one Cardiovascular syndrome 1.1 heart rate (beats / min) 74.7 ± 4.1 68.8 ± 3.9 73.7 ± 4.2 74.5 ± 4.1 1.1.1 the number of patients with tachycardia,% 46.6 6.6 43.3 40,0 1.1.2 the number of patients with bradycardia,% 40,0 3.3 36.6 33.3 1.1.3 the presence of transient arrhythmia (extrasystole),% 16.6 0 20,0 20,0 1.2 the number of patients with labile blood pressure,% 100.0 10.0 100.0 93.3 including hypotonic type (HELL≤110 / 70),% 43.3 3.3 40,0 33.3 hypertonic type (HELL≥130 / 90),% 56.6 6.6 60.0 56.6 1.3 the presence of cardialgia (pressing, stitching, throbbing pain in the heart),% 80.0 10.0 76.6 70.0 1.4 the presence of discomfort in the precardial region,% 83.3 10.0 80.0 83.3

Continuation of table 3 No. p / p Main characteristics The main group n = 30 Control group n = 30 At the beginning of observation At the end of observation At the beginning of observation At the end of observation 1.5 the presence of pathological vasomotor reactions: 1.5.1 skin color change (pallor, cyanosis, hyperemia),% 26.6 3.3 33.3 30,0 1.5.2 limb chilliness,% 20,0 0 23.3 23.3 2 Hyperventilation syndrome,% 2.1 the presence of psychogenic shortness of breath 16.6 0 20,0 16.6 2.2 the presence of cough 13.3 0 16.6 13.3 2.3 the number of patients with a history of fainting 10.0 3.3 13.3 10.0 3 Abdominal syndrome,% 3.1 abdominal pain (conditional points) 4.6 ± 0.9 0 4.7 ± 0.9 4.1 ± 0.8 3.2 flatulence 66.6 3.3 63.3 60.0 3.3 burping air 43.3 3.3 46.6 40,0 3.4 nausea, vomiting 23.3 0 23.3 20,0 3.5 lack of appetite 73.3 10.0 70.0 63.3 3.6 stool dysfunction (constipation, diarrhea) 26.6 6.6 23.3 20,0

As can be seen from the tables, the vast majority of patients after the course of taking the pharmaceutical composition in the form of tablets showed a positive dynamics of neurotic, cognitive and emotional-affective disorders (Table 2), autonomic disorders (Table 3).

Clinical trials on the use of a pharmaceutical composition in the form of tablets in patients with vegetovascular dystonia (psycho-vegetative syndrome) showed that its introduction to complex therapy has reduced mental and somatic manifestations of anxiety, increased the adaptive capabilities of patients and improved their quality of life: regain self-confidence, remove stress and internal stress and, as a result, normalize sleep.

Reduction or elimination of anxiety (preoccupation, bad premonitions, fears, irritability), tension (timidity, tearfulness, anxiety, inability to relax, insomnia, fear), and therefore vegetosomatic symptoms: cardiovascular (lability of pulse and blood pressure, cardiac disturbance rhythm, cardialgia, discoloration of the skin, chills of the extremities), respiratory (psychogenic shortness of breath, cough, yawning, deep breaths), gastrointestinal (nausea, vomiting, flatulence, belching, pain, dysfun tion of the chair), cognitive disorders (difficulty concentrating, memory loss), has been observed at 5-7 days of drug treatment.

The drug has no muscle relaxant properties, it does not cause drowsiness or addiction.

For the first time, a drug was created that combines the sedative, cardiotonic and hypotensive effects of motherwort, the anti-anxiety effect of the "calm element" of magnesium and the positive effect of vitamin B6, which normalizes the functioning of the central and peripheral nervous system. Dosage forms based on the claimed composition are intended for use as mild anxiolytic and sedative agents of daytime action, since they do not cause drowsiness.

The applicant also conducted comparative studies of the claimed drug with drugs available on the market, namely, Pustyrniki tablets and Magne B6 tablets in patients with vegetovascular dystonia.

The results of the studies convincingly showed that the use of the drug according to the invention contributed to a more significant improvement in patients with vegetovascular dystonia than in groups receiving a single drug from motherwort extract or combined preparation Magne B6, i.e. The claimed preparation is more effective not due to a simple summation of effects, but due to potentiation, when the total effect exceeds the simple addition of the effects of each component. The drug according to the invention has a prolonged effect, it is enough to take it in a dose of 1 tablet per day, morning and evening. Comparison preparations should be taken more often (Motherwort extract 1 tablet 4 times a day) and at a higher dosage (Magne B6 2 tablets 3 times a day).

Claims (3)

1. A pharmaceutical composition of sedative and anxiolytic effects, containing motherwort extract and excipients, characterized in that it further comprises at least one pharmaceutically acceptable compound of magnesium and vitamin B ₆ in the following ratio, wt.%:
motherwort extract 2.8-10 magnesium compound 20-50 vitamin B ₆ 0.1-1 Excipients up to 100 2. The pharmaceutical composition according to claim 1, wherein the pharmaceutically acceptable magnesium compound is selected from the group: carbonate, sulfate, lactate, orotate, or citrate. 3. The pharmaceutical composition according to claim 1, where it is made in the form of a tablet, capsule or sachet.