RU2440132C2 - Composition exhibiting neuroprotective, antiamnestic, antihypoxic and antiischemic activity - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, namely a composition containing semax in amount 0.0001-0.03 g and mexidol in amount 0.4-5.0 g as active ingredients, ammonium acetate, 1 M acetic acid to pH 4.5-5.5 and water for injections.

EFFECT: creation of the composition exhibiting high neuroprotective, antiamnestic, antihypoxic and antiischemic activity combined with antiemetic activity.

7 tbl, 9 ex

Description

The invention relates to medicine, specifically to a pharmaceutical composition having neuroprotective, antiamnestic, antioxidant and anti-ischemic activity.

One of the urgent problems of modern neurology is the development of means to protect the central nervous system by activating various metabolic processes of the brain. The relevance of the development of new drugs with neuroprotective activity is determined by the high mortality from stroke.

Known heptapeptide "Semax" with high neuroprotective activity [1].

Known drug mexidol, which has similar activity [2].

Mexidol and Semax are currently widely used in various fields of medicine. So, for example, both drugs are used in neurology for acute and chronic cerebrovascular insufficiency and related diseases, including cerebral stroke and its consequences [1-4]. However, in the clinic, Mexidol and Semax are not always effective.

The technical result of the invention is the expansion of the arsenal of drugs, the creation of a composition having high neuroprotective, antiamnestic, antihypoxic, antioxidant and antiischemic activity in combination with antiemetic activity.

The specified technical result is achieved due to the fact that the composition having neurotropic, antiamnestic, antihypoxic and antiischemic activity contains semax and mexidol as active components, ammonium acetate, 1 M acetic acid and water for injection, in the following ratio, g: mexidol 0.4-5.0; semax 0.0001-0.03; ammonium acetate - 0.71; 1 M acetic acid - up to pH 4.5-5.5; water for injection - up to 1 liter.

In addition, the composition can be performed in lyophilized form. The invention is illustrated by the following examples.

Example 1. In a reactor equipped with an anchor stirrer, pour 8 l of water for injection. Then the valve is opened to supply sterile nitrogen to the reactor and water is bubbled for 5 minutes. After that, 6 g of the substance of Mexidol and 5 mg of the substance of Semax are successively loaded into the reactor with constant stirring and bubbling of the solution with nitrogen. Mixing lead to complete dissolution. Then, the pH of the solution was adjusted to a value of 4.5-5.5 by the addition of a 1 M solution of acetic acid. The resulting solution was adjusted to a volume of 10 l with water for injection and passed through a sterilizing filter. Under aseptic conditions, bottling in ampoules with a capacity of 2 ml, 1 ml per ampoule, is carried out. Cartridges with ampoules are placed in a sublimation chamber, where they are frozen to a temperature of minus 40 ° С with a freezing rate of 10 ° С / h, and then subjected to drying by vacuum. Ampoules with the obtained dry lyophilized form of the drug are sealed under nitrogen.

Example 2. 6 g of the substance of Mexidol and 40 mg of the substance of Semax are dissolved with stirring and sparging with nitrogen in 8 l of water for injection, in which 0.71 g of ammonium acetate is previously dissolved, the pH of the resulting solution is adjusted to a value of 4.5-5.0 s using a 1 M solution of acetic acid and add water for injection to a total volume of 10 l. Sterilized filtration of the resulting solution is carried out and under aseptic conditions, it is bottled under nitrogen in ampoules with a capacity of 2 ml of 1 ml in an ampoule. Filled ampoules are sealed under nitrogen.

The pharmacological activity of the described composition was studied experimentally by known methods [5].

Example 3. Antihypoxic effect of the composition containing Mexidol and Semax as active components in a model of acute normobaric hypoxic hypoxia with hypercapnia (in a heat chamber) (Table 1)

The studies were performed on white nonlinear male mice with an average weight of 22 ± 1 g according to a known method [5].

Acute normobaric hypoxic hypoxia with hypercapnia was reproduced by placing mice (individually) in a heat chamber: animals were placed in glass jars of the same volume (250 cm ³ ), which were hermetically sealed. As oxygen was consumed, its concentration in the air of the vessel and in the body decreased, and the amount of carbon dioxide, on the contrary, increased. As a result, animals developed acute hypoxic hypoxia with hypercapnia. The life expectancy of mice was recorded with a stopwatch (until breathing stopped) in a heat chamber in minutes (accurate to 0.1 minutes) and the increase in the efficacy of the tested pharmacological substances was judged. The test substances and isotonic sodium chloride solution (control) were administered intraperitoneally before the animals were placed in the chamber. The results are presented in table 1.

It was found that mexidol at doses of 30 and 50 mg / kg did not significantly affect, and at a dose of 100 mg / kg significantly (p <0.05) increased the life expectancy of animals in acute normobaric hypoxia with hypercapnia by 27%. Semax in doses of 0.025 and 0.2 mg / kg practically did not change the life expectancy of mice in a heat chamber. When using the composition with Mexidol and Semax, they caused a tendency in three cases (Mexidol 30 mg / kg + Semax 0.025 mg / kg, Mexidol 30 mg / kg + Semax 0.2 mg / kg and Mexidol 50 mg / kg + Semax 0.025 mg / kg) or in other tested doses significantly (p <0.05) increased the life expectancy of animals by 22% (Mexidol 50 mg / kg + Semax 0.2 mg / kg) and 33% (Mexidol 50 mg / kg + Semax 0.025 mg / kg).

From table 1 it is seen that the use of a composition with the content of Mexidol and Semax in its composition leads to an increase in life expectancy, more significant than with separate use of these drugs in the same doses. A sharp increase in the effectiveness of the effects of the composition with the combined use of Mexidol and Semax as active components does not occur due to an increase in the dosages of these active components with a minimum negative effect of these drugs.

Example 4. Anti-ischemic effect of the composition containing Mexidol and Semax as active components in the model of circulatory hypoxia of the brain (Table 2)

The studies were performed on white non-linear male mice weighing 31-38 g (age 11-13 months).

Circulatory hypoxia of the brain (cerebral ischemia) was reproduced by simultaneous ligation (under ether anesthesia) of both common carotid arteries. In false-operated animals (control group), the operation was limited to the stage of access to the common carotid arteries. Animals after surgery were observed for several weeks. The studied substances (semax, mexidol) and isotonic sodium chloride solution (control) were administered intraperitoneally for 7 days: on the first day after ligation and 3 hours after surgery, on the remaining 6 days - 1 time per day.

After bilateral ligation of the common carotid arteries, mice died during the first 6 days.

From table 2 it is seen that the survival rate of animals in the control group after 6 days after bilateral ligation of the common carotid arteries was 78% (of 117 killed 26 mice). Mexidol at a dose of 100 mg / kg significantly (p <0.05) increased the number of surviving mice to 97%, i.e. had an almost complete protective effect. Mexidol at a dose of 30 mg / kg and semax (0.025 and 0.2 mg / kg), the survival of animals was not significantly changed. However, when using the composition with the active components (Mexidol + Semax) in the indicated doses, they significantly (p <0.05) increased the number of surviving mice to 96-97% (Table 2).

Example 5. Antiamnestic effect of the composition containing Mexidol and Semax as active components in the model of amnesia caused by electroconvulsive shock (Table 3)

The effect of the composition of Mexidol and Semax on the learning and memory processes was studied on white nonlinear male mice (weighing 20-24 g) using the conditional passive avoidance reaction (passive avoidance reaction) of electrodermal irritation [6]. At present, the passive avoidance reaction test is a basic model for assessing the effect of substances on the formation and reproduction of a commemorative footprint under normal conditions and under conditions of its disruption (amnesia), as well as the most informative methods for assessing the effectiveness of substances with nootropic activity [5]. The installation for mice was a black experimental chamber measuring 30 × 40 × 30 cm with an electrode floor and a white plastic platform (7.5 × 7.5 × 0.5 cm), which was placed on the floor in the center of the chamber. Mice (alone) were placed on a plastic platform. Usually, animals descended (or jumped) from the platform onto the electrode floor, where they received a “punishment” - an electric shock (at this time a constant electric current of 0.8 mA was applied to the chamber floor). Electric current was turned on only when the mouse touched the floor with all four limbs. The usual reaction of animals was to return to a safe platform. After 5 minutes of training, passive avoidance reaction was developed in mice — they remained on the platform. Testing for the safety of passive avoidance reaction was carried out 24 hours after the amnesiac effect. Moreover, if the animal left the platform within 1 minute, he observed retrograde amnesia of the passive avoidance skill.

An electroconvulsive shock (electric current parameters: 50 Hz, 50 mA, 0.3 s), which was applied to mice using clip-type electrodes fixed on the auricles (transpineally) immediately after learning of passive avoidance reaction, was used as an amnesic effect [5]. In animals of the control group, pseudoelectroconvulsive shock was caused: pinneal electrodes were applied to apply electroconvulsive shock without applying an electric current. Pharmacological substances were administered intraperitoneally during the period of generalized seizures caused by electroconvulsive shock, i.e. immediately after electroconvulsive shock. Testing mice for the preservation of passive avoidance reaction was performed 24 hours after electroconvulsive shock.

It was found that electroconvulsive shock in most mice caused retrograde amnesia of passive avoidance skill: in 82% of animals (p <0.001), passive avoidance amnesia was observed after 24 hours. Mexidol at a dose of 100 mg / kg completely prevented the development of amnesia of passive avoidance reaction. Mexidol at a dose of 30 mg / kg and semax at a dose of 0.2 mg / kg did not significantly change the amnestic effect. However, when they were used, the compositions (with the active components Mexidol + Semax) at the indicated doses significantly (p <0.05) weakened the amnestic effect by 2 times (Table 3).

From table 3 it is seen that the use of a composition containing Mexidol and Semax as active components leads to a decrease in the amnestic effect, more significant than with separate use of these drugs in the same doses. A sharp increase in the effectiveness of the effect with the combined use of Mexidol and Semax in the composition does not occur due to an increase in the dosages of these active components with a minimal negative effect of these drugs.

Example 6. Antiamnestic effect of a composition containing Mexidol and Semax as active components on the model of amnesia caused by swimming of mice in cold water with the simultaneous rotation of the wheel to exhaustion (table 4)

The studies were performed on white nonlinear male mice weighing 20-24 g using the development of passive avoidance reaction in animals (described in example 5).

Animals (individually) were placed in a plastic box filled with water 17 × 9 × 19 cm in size with a rotating ribbed wheel. Swimming mice in cold water with the simultaneous rotation of the wheel to exhaustion (PMHV) was used immediately after learning passive avoidance reaction. The safety of passive avoidance reaction was checked 24 hours after the end of PMHV. In this case, the most pronounced mnestic disturbances were observed in mice when they swam in water (on average 10.6 min), which had a temperature of 12-14 ° C, and the room temperature was 16-20 ° C. The animals were placed in wet cold sawdust as a false PMHV.

It was found that PMHV caused retrograde amnesia of the passive avoidance skill in most mice: in 62% of the animals (p <0.001), passive avoidance amnesia was observed after 24 hours. Mexidol at a dose of 100 mg / kg completely prevented the development of amnesia of passive avoidance reaction. Mexidol at a dose of 10 mg / kg and semax at a dose of 0.025 mg / kg did not significantly affect amnesia of passive avoidance reaction. However, when using the composition (with the active components - Mexidol + Semax), they at the indicated doses significantly (p <0.05) weakened the amnestic effect by 2.1 times (Table 4).

From table 4 it is seen that the use of a composition containing Mexidol and Semax as active components leads to a weakening of the amnestic effect, more significant than with separate use of these drugs in the same doses. A sharp increase in the effectiveness of the effect when used in the composition as the active components of Mexidol and Semax does not occur due to an increase in the dosages of the individual active components with a minimum negative effect of these drugs.

Example 7. Anti-amnestic effect of the composition with the active components Mexidol and Semax on the model of amnesia caused by swimming of mice with bandaged common carotid arteries in cold water with the simultaneous rotation of the wheel to exhaustion (table 5)

On the model of amnesia caused by PMHV, the efficacy of drugs in mice with bandaged common carotid arteries was evaluated (see Example 4). After 6-10 days after the operation, the surviving animals practically did not differ from the control (falsely operated, n = 20) according to the orientational research reaction and emotional status (open field test). In this regard, they were used in the passive avoidance reaction test (described in Example 5). Testing for the safety of passive avoidance reaction was carried out 24 hours after amnesic exposure (PMHV). The test substances and isotonic sodium chloride solution (control) were administered intraperitoneally (see above; the last time was administered semax 10 minutes, mexidol 60 minutes before training mice).

It was established that PMHV caused retrograde amnesia of passive avoidance skill in most mice with bandaged common carotid arteries: passive avoidance amnesia was observed in 65% of animals (p <0.001) after 24 hours. Mexidol at a dose of 100 mg / kg reduced the severity of amnesia by 2.2 times (p <0.05). Semax (0.025 mg / kg) and Mexidol (30 mg / kg) did not significantly affect amnesia of passive avoidance reaction. However, with their combined use (Mexidol + Semax) they significantly (p <0.05) had a clear antiamnestic effect, reducing the severity of amnesia by 1.8 times (Table 5).

From table 5 it is seen that the use of a composition containing Mexidol and Semax as active components leads to an increase in anti-amnestic effects, more significant than with separate use of these components in the same doses. A sharp increase in the effectiveness of the effect when combined with Mexidol and Semax in the composition does not occur due to an increase in the dosages of the individual components with minimal negative effects of these drugs.

Example 8. Antiamnestic effect of the composition on the model of amnesia caused by acute normobaric hypoxic hypoxia with hypercapnia (in a heat chamber) (Table 6)

The studies were performed on white nonlinear male mice weighing 20-24 g using the development of passive avoidance reaction in animals (described in example 5).

The model of acute normobaric hypoxic hypoxia with hypercapnia described in Example 3 was also used to induce passive avoidance skill in animals with retrograde amnesia. For this, mice immediately after training passive avoidance reaction were placed (individually) in the heat chamber for 16-18 minutes depending on the severity of the symptoms of oxygen deficiency and weight (the more weight, the usually less time spent in the heat chamber). In the control group, animals were subjected to false hypoxia - mice were placed in glass jars of the same volume, which were not covered. The preservation of passive avoidance reaction was performed 24 hours after the end of exposure to hypoxia with hypercapnia. The substances were administered intraperitoneally (Mexidol - 60 minutes, Semax - 10 minutes) before training mice.

It was found that 24 hours after a 16-18 minute stay of mice in a heat chamber, most of them had retrograde amnesia: in 64% of animals (p <0.001). Mexidol (100 mg / kg) completely prevented the development of amnesia of passive avoidance reaction. Mexidol at a dose of 30 mg / kg and semax at doses of 0.025 and 0.2 mg / kg did not significantly affect amnesia of passive avoidance reaction. However, with their combined use (Mexidol + Semax) they significantly (p <0.05) had a clear antiamnestic effect, reducing the severity of amnesia by 1.7-2.1 times (Table 6).

From table 6 it is seen that the use of a composition containing Mexidol and Semax as the active components leads to an increase in the antiamnestic effect, more significant than with separate use of these drugs in the same doses. A sharp increase in the effectiveness of the effect with the combined use of mexidol and semax in the composition does not occur due to an increase in the dosages of these components with a minimal negative effect of these drugs.

As a result of the studies, it was found that the proposed composition with the content of components in the indicated amounts has a pronounced neuroprotective, antiamnestic, antihypoxic and antiischemic activity and can be used to create new drugs for the treatment of pathologies of the central nervous system. In this case, there is a synergistic effect, manifested when the composition of the composition is used as the active components of semax and mexidol, which is significantly higher than the efficiency of the separate use of these components

Table 1 The effect of the composition of Mexidol and Semax on the life expectancy of mice in a heat chamber (M ± m) Substance (dose, mg / kg) The number of mice Life span, minutes Isotonic sodium chloride solution (control) 16 28.1 ± 1.0 Mexidol (30) 10 29.0 ± 1.5 Mexidol (50) 10 30.9 ± 1.6 Mexidol (100) 16 35.6 ± 3.1 * Semax (0,025) 10 28.9 ± 1.1 Semax (0.2) 10 29.8 ± 1.2 Mexidol (30) + semax (0,025) 12 31.7 ± 2.1 Mexidol (30) + semax (0.2) 10 32.9 ± 2.4 Mexidol (50) + semax (0,025) 12 33.1 ± 2.3 Mexidol (50) + semax (0.2) fourteen 34.2 ± 2.0 * Mexidol (100) + semax (0.025) fourteen 37.3 ± 3.2 * Note. * - p <0.05 - differences are statistically significant compared with the control (student criterion)

table 2 The effect of the composition of Mexidol and Semax on the survival of mice 6 days after bilateral ligation of the common carotid arteries Substance (dose, mg / kg) The number of mice The number of surviving mice (%) Isotonic sodium chloride solution (control) 117 91 (78) Mexidol (100) 29th 28 (97) * Mexidol (30) twenty 18 (90) Semax (0,025) 23 20 (87) Semax (0.2) 25 23 (92) Mexidol (30) + semax (0,025) 28 27 (96) * Mexidol (30) + semax (0.2) 31 30 (97) * Note. * - p <0.05 - significance of differences compared with control (Fisher's exact method)

Table 3 The effect of the composition of Mexidol and Semax on amnesia in mice caused by electroconvulsive shock (ESH) Test conditions and substance (dose, mg / kg) Total number of mice The number of mice trained passive avoidance reaction (%) The number of mice with amnesia passive avoidance reaction after 24 hours after amnesic exposure (%) Isotonic sodium chloride solution + pseudo-ESH (control 1) thirty 27 (90) 5 (19) Isotonic sodium chloride solution + ESH (control 2) thirty 28 (93) 23 (82) ^ooo Mexidol (30) + ESH eleven 10 (91) 5 (50) Mexidol (100) + ESH 21 20 (95) 4 (20) *** Semax (0.2) + ESH eleven 10 (91) 7 (70) Mexidol (30) + semax (0.2) + ESH 24 22 (92) 9 (41) * Note. The differences are statistically significant compared to control 1 and control 2, respectively (Fisher's exact method):
° or * - p <0.05, ^ooo or *** - p <0.001.

Table 4 The effect of the composition of Mexidol and Semax on the amnestic effect caused in mice with bandaged common carotid arteries by swimming in cold water with the simultaneous rotation of the wheel to exhaustion (PMHV) Test conditions and substance (dose, mg / kg) Total number of mice The number of mice trained passive avoidance reaction (%) The number of mice with amnesia of passive avoidance reaction 24 hours after PMHV (%) Isotonic sodium chloride solution + false PMHV (control 1) 52 48 (92) 8 (17) Isotonic solution of sodium chloride + PMHV (control 2) 55 52 (94) 32 (62) ^ooo Mexidol (10) + PMHV 19 17 (89) 8 (30) ^o Mexidol (100) + PMHV twenty 19 (95) 3 (16) *** Semax (0.025) + PMHV 22 20 (91) 8 (40) Mexidol (10) + semax (0.025) + PMHV 22 21 (95) 6 (29) * Note. The differences are statistically significant compared to control 1 and control 2, respectively (Fisher's exact method):
° or * - p <0.05, ^ooo or *** - p <0.001.

Table 5 The effect of the composition of Mexidol and Semax on the amnestic effect caused in mice with bandaged common carotid arteries by swimming in cold water with the simultaneous rotation of the wheel to exhaustion (PMHV) Test conditions and substance (dose, mg / kg) Total number of mice The number of mice trained passive avoidance reaction (%) The number of mice with amnesia of passive avoidance reaction 24 hours after PMHV (%) Isotonic sodium chloride solution + false PMHV (control 1) 34 29 (85) 6 (21) Isotonic solution of sodium chloride + PMHV (control 2) 47 40 (85) 26 (65) °°° Mexidol (100) + PMHV 25 23 (92) 7 (30) * Mexidol (30) + PMHV 19 17 (89) 8 (47) Semax (0.025) + PMHV fifteen 13 (87) 7 (54) Mexidol (30) + semax
(0,025) + PMHV 24 22 (92) 8 (36) * Note. The differences are statistically significant compared to control 1 and control 2, respectively (Fisher's exact method):
° or * - p <0.05, ^ooo or *** - p <0.001.

Table 6 The effect of the composition of Mexidol and Semax on amnesia in mice caused by acute normobaric hypoxic hypoxia with hypercapnia Test conditions and substance (dose, mg / kg) Total number of mice The number of mice trained passive avoidance reaction (%) The number of mice with amnesia passive avoidance reaction after 24 hours after amnesic exposure (%) Isotonic sodium chloride solution + false hypoxia (control 1) thirty 28 (93) 5 (18) Isotonic sodium chloride solution + hypoxia (control 2) 48 44 (92) 28 (64) °°° Mexidol (30) + hypoxia 12 11 (92) 5 (45) Mexidol (100) + hypoxia 17 16 (94) 3 (19) ** Semax (0.025) + hypoxia eleven 10 (91) 6 (60) Semax (0.2) + hypoxia eleven 10 (91) 5 (50) Mexidol (30) + semax (0.025) + hypoxia 26 24 (92) 9 (38) * Mexidol (30) + semax (0.2) + hypoxia 21 20 (95) 6 (30) * Note. The differences are statistically significant compared to control 1 and control 2, respectively (Fisher's exact method):
^o or * - p <0.05, ^oo or ** - p <0.01, ^ooo or *** - p <0.001.

Example 9. Antiemetic effect of the composition (table. 7)

The studies were performed on 13 male cats weighing 3.1-4.2 kg, which were in free behavior. Xylazine, which is traditionally used to induce vomiting in cats, was used as an emetic agent [7]. Xylazine was administered to animals intramuscularly (IM) at a dose of 0.66 mg / kg [7]. The latent period (PL) of the emetic reaction and the number of emetic acts were recorded within 1 hour after the intramuscular administration of xylazine (since animals usually experienced repeated vomiting). Mexidol, semax, their composition and isotonic sodium chloride solution (control) were administered (twice) to the animals subcutaneously 4 hours and 45 minutes before the administration of xylazine.

In the first series of experiments conducted on 6 male cats, it was found that individually neither Mexidol at a dose of 100 mg / kg (2 times at 50 mg / kg), nor Semax at a dose of 0.4 mg / kg (2 times at 0.2 mg / kg) do not possess antiemetic activity (Table 7).

In the II series of experiments conducted on 7 animals, it was found that the composition with Mexidol and Semax (2 times 50 and 0.2 mg / kg, respectively) compared with the control significantly (p <0.05) increases the drug by 2 times emetic reaction and by 43% reduces the number of emetic acts (Table 7). Therefore, this composition, in contrast to its active components, has antiemetic activity.

Table 7 The effect of the composition of Mexidol and Semax on vomiting caused by xylazine in cats Test conditions and substance (dose, mg / kg) Number of cats Latent period of emetic reaction, minutes (M + m) The number of vomiting acts (M + m) Isotonic sodium chloride solution + xylazine (control) 6 6.7 ± 1.1 3.0 ± 0.6 Mexidol (50-2 times) + xylazine 6 9.9 ± 1.3 2.0 ± 0.4 Semax (0.2-2 times) + xylazine 6 8.8 ± 1.1 2.8 ± 0.3 Isotonic sodium chloride solution (2 times) + xylazine (control) 7 6.5 ± 0.7 3.7 ± 0.3 Mexidol (50-2 times) + semax (0.2-2 times) + xylazine 7 13.3 ± 1.6 * 2.1 ± 0.3 * Note. The differences are statistically significant compared with the control (paired Wilcoxon test and student criterion): * - p <0.05.

As a result of studies, it was found that the described pharmaceutical pharmaceutical composition has a high neuroprotective activity in combination with antiamnestic, antihypoxic, antioxidant, antiischemic and antiemetic activity.

Literature

1. RF patent No. 29 22514 (2005).

2. The Register of Medicinal Products of Russia. Encyclopedia of Medicines -14 vol. - M., Radar-2006-p. 488-489.

3. Gusev E.I., Skvortsova V.I. Cerebral ischemia. - M .: Medicine, 2001.

4. Fedin A.I., Rumyantseva S.A., Mironova O.P., Evseev V.P. The use of the antioxidant Mexidol in patients with acute cerebrovascular accident. Guidelines. - M., 2002 .-- 16 p.

5. Voronina T.A., Ostrovskaya R.U. Guidelines for the study of the nootropic activity of pharmacological substances // Guide to the experimental (preclinical) study of new pharmacological substances. / Ed. Fisenko V.P. -M., 2000.-S.153-158.

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7. But SM., But S.T., Wang J.J. et al. Effects of dexamethasone on emesis in cats sedated with xylazine hydrochloride // Am J Vet Res. - 2001. - Vol. 62, N 8. - P. 1218-1221.

Claims (1)

A composition having neurotropic, antiamnestic, antihypoxic and antiischemic activity, characterized in that it contains semax and mexidol as active components, ammonium acetate, 1 M acetic acid and water for injection in the following ratio of components, g:
Mexidol 0.4-5.0
semax 0.0001-0.03
ammonium acetate 0.71
1M acetic acid to pH 4.5-5.5
water for injection up to 1 l