RU2096034C1 - Pharmaceutical composition inducing glutathione biosynthesis, glutathione transferase activity and showing antitoxic, radioprotective and antihypoxic action and methods of treatment, prophylaxis and protection using thereof - Google Patents

Abstract

FIELD: medicine, biochemistry. SUBSTANCE: pharmaceutical composition has pharmaceutically acceptable carrier and an active component - effective amount of a mixture of L-glutamic acid, glycine and sulfur-containing amino acid taken from the group including cysteine, cystine and methionine at mass ratio of components = 1:1:1. Pharmaceutical composition can be prepared in the form of powder, tablet or solution. It has each of the indicated components at amount 0.1-0.2 g per a single dose. Pharmaceutically acceptable carrier consists of water or methylcellulose. Composition is used for prophylaxis and treatment of chronic alcoholism, intoxication with aromatic hydrocarbons and for resistance increase to hypoxia and protection from radiation damage by sublingual administration at effective dose. EFFECT: enhanced effectiveness of composition. 8 cl, 1 dwg , 11 tbl

Description

 The invention relates to medicine, and more specifically relates to a new drug that induces the biosynthesis of glutathione, the activity of glutathione transferase and has an antitoxic, radioprotective and antihypoxic effect.

 It is known that the resistance of living organisms is largely provided by the glutathione-conjugating system through the detoxification of xenobiotics, endogenous toxic compounds, free radicals, as well as participation in redox processes and maintaining the pool of SH-groups.

 Currently, due to the sharp deterioration of the ecological and radiological situation, the search for completely safe pharmaceutical preparations based on natural metabolites, which increase the body's resistance through selective induction of glutathione biosynthesis and the enzyme complex interacting with it, is of particular importance. However, there are no drugs in medical practice. Attempts are being made to use glutathione or its derivatives directly in practical medicine (News of the Academy of Sciences of the Latvian SSR, 1984, N 12/449 /, Zinatne, Riga, p. 77-92; Pharmacology and Toxicology, 1972, v. 4, p. 473- 474; JP 6 304404; JP 7118730; DE 1443335; DE 2329819). However, this tripeptide does not have an inducing effect on the glutathione-conjugating system (American Journal of Physiology, 1992, N 2, v. 32, American Physiological Society, Bethesda, USA, p. 348-352), does not always have the desired effect due to its poor tissue penetration (Annual review of biochemistry, 1983, v. 52, Annual reviews Ins. Paloalto, California, USA, p. 711-760; International Journal of Biochmistry, 1980, N 4, v. 12, Pergamon Press, Oxford New York Paris Frankfurt, p. 545-551), is used in high doses and has a significant cost, which excludes the possibility of its widespread use in medical practice.

 The inventive pharmaceutical composition is new and is not described in the literature.

 The basis of the invention is the creation of a new highly effective, non-toxic, non-side effects composition that selectively induces the biosynthesis of glutathione, the glutathione-conjugating system and has an antitoxic, radioprotective and antihypoxic effect.

 The problem is solved in that the claimed composition, comprising the active substance and a pharmaceutical carrier or solvent, according to the invention contains as an active substance a mixture of L-glutamic acid, glycine and one of the sulfur-containing amino acids: cysteine or cystine, or methionine, or their pharmaceutically acceptable salts in weight ratio of 1: 1: 1.

 The pharmaceutical composition may be used in the form of a powder, solution or tablets. Preferably, it is applied in the form of a powder or tablets sublingually with an active substance content of 0.1-0.2 g of each ingredient or its pharmaceutically acceptable salt per therapeutic dose. Preferably, the pharmaceutical composition contains methyl cellulose as a pharmaceutical carrier and water as a solvent.

 The claimed pharmaceutical composition has a highly effective inducing biosynthesis of glutathione and glutathione conjugating system, has an antitoxic, radioprotective and antihypoxic effect and is used for the prevention and treatment of chronic alcoholism, alcohol withdrawal, intoxication in the chemical industry, various forms of chemical, muscle and hypoxic hypoxia, and the birth of a child, myocardial ischemia, pneumonia, and also as a radioprotectant and for people who are in areas with high levels of radiation, especially for pregnant women and their fetus.

 The invention is illustrated by the drawing, which shows the effect of the claimed composition, including cysteine or cystine and various doses of glutathione, on the survival of rats after γ-irradiation in a lethal dose of 10 Gy.

 The inventive composition is a mixture of L-glutamic acid, glycine and one of the sulfur-containing amino acids: cysteine or cystine, or methionine. These amino acids are natural metabolites found in plant and animal tissues, and they are odorless white powdered substances (sulfur-containing amino acids have a specific smell of mercapto compounds), they are readily soluble in water (L-glutamic acid and methionine are sparingly soluble), in alkaline solutions, it is difficult soluble in ethyl alcohol and oils.

 The pharmacological effect of the claimed composition was studied in an experiment on animals and in a clinic on human volunteers.

 Inducing glutathione biosynthesis and glutathione S-transferase activity of the claimed composition was studied on sexually mature male rats and Wistor females weighing 180-200 g.

 The effect of various doses of the claimed composition on the biosynthesis of glutathione and the activity of glutathione S-transferase in the liver of male Wistor rats was studied. Experimental animals 30 minutes before decapitation under the root of the tongue sublingually introduced various doses of the claimed composition in a volume of 0.5 ml of distilled water. The control group of animals was sublingually injected only with the appropriate volume of water. The liver was homogenized, and its microsomal and post-microsomal subfractions were obtained by differential centrifugation. The total content of glutathione was measured by the methods of Ellman, Griffith. (Archives of biochemistry and biophysics, 1959, N 1, v. 82, Academic Press, Inc. New York, USA, p. 70-77; Analytical Biochemistry, 1980, N 1, v. 106, Academic Press, Inc. New York London, p. 207-212), and glutathione S-transferase activity by the method of Habig et al. (The journal of biological chemistry, 1974, No. 22, v. 249, American Society of Biological Chemistry, Inc. Baltimore, USA, p. 7130-7139) using I-chloro-2,4-dinitrobenzene as a substrate. The results of the study are given in table. one.

 As can be seen from the table. 1, the dose of the claimed composition of 6 mg / kg of animal weight is optimal for the induction of both glutathione biosynthesis and glutathione S-transferase activity.

 In the liver of Wistor rats, the glutathione biosynthesis inducing biosynthesis and glutathione S-transferase activity of glutathione at a dose of 6 mg / kg weight, cysteine at a dose of 2 mg / kg weight and the optimal dose (6 mg / kg weight) of the claimed composition, including sulfur-containing amino acids cysteine or cystine, or methionine. The data obtained are presented in table. 2.

 The data table. 2 show that neither the tripeptide itself, nor its individual precursor practically does not affect the content of glutathione and the activity of glutathione S-transferase, while the claimed composition induces both biosynthesis of the tripeptide and the enzymatic activity of glutathione S-transferase.

 The content of glutathione already 30 minutes after the introduction of the claimed composition increased in the liver of animals in 2.7; 1.9 and 1.8 times for a composition comprising cysteine or cystine, or methionine, respectively, compared with the theoretically calculated, i.e., its content, provided that the ingredients of the claimed composition are quantitatively used in an equimolar ratio only by the liver (average weight is 4 g) of animals for biosynthesis of glutathione.

 In addition, after the introduction of the claimed composition, an increase in the activity of the membrane-bound form of glutathione S-transferase by 1.5 times and cytosolic by 1.2 times for a composition comprising cysteine was observed; 1.3 and 1.4 times, respectively, for a composition comprising cystine, and 1.3 and 1.2 times, respectively, for a composition comprising methionine.

 Thus, the claimed composition has a pronounced inducing effect on the glutathione-conjugating system, and the magnitude of this effect is determined by the sulfur-containing ingredients used, which are located as it weakens in the following sequence: cysteine> cystine> methionine.

The antitoxic effect of the claimed composition was studied on sexually mature male Wistjr rats weighing 180-200 g. The first group of experimental animals 30 minutes before the administration of per os chlorobenzene in a dose of LD ₅₀ , which is 1500 mg / kg for the rats used, sublingually introduced under the tongue root the claimed composition in a dose of 6 mg / kg; the second and third groups of experimental animals 30 minutes before the administration of chlorobenesol in the same dose sublingually glutathione was administered in doses of 6 and 100 mg / kg of weight, respectively; the control group of animals 30 minutes before the introduction of chlorobenzene in the same dose was injected with an appropriate volume of water. The results of the study are given in table. 3.

 As can be seen from the table. 3, the preliminary introduction to animals of the claimed composition causes a sharp decrease in the toxic effect of chlorobenzene. Moreover, the antitoxic effect of the tripeptide is much less pronounced than that of its predecessors.

 The anti-alcohol effect of the claimed composition was studied in male rats of the Wistor line. The first group of experimental animals of the claimed composition was administered sublingually at a dose of 6 mg / kg of body weight 2 hours before intraperitoneal administration of a 25% solution of ethanol at a dose of 4.5 mg / kg of body weight; the second and third groups of experimental animals 2 hours before the intraperitoneal administration of ethanol in the same dose was administered sublingually glutathione in doses of 6 and 100 mg / kg, respectively; the control group of animals 2 hours before the intraperitoneal injection of ethanol in the same dose was injected with an appropriate volume of water. Animals were decapitated 2 hours after the introduction of alcohol, and the glutathione content was determined in the liver by the above-described methods and the activity of glutathione S-transferase was measured. The data obtained are presented in table. 4.

 The data table. 4 show that the claimed composition has an alkoprotective detoxifying effect, preventing the depletion of the pool of endogenous glutathione, and its antitoxic effect is much more pronounced than that of the tripeptide.

The radioprotective effect of the claimed composition was studied on sexually mature male Wistor rats weighing 180-200 g and sexually mature female white rats weighing 180-200 g. Rats were exposed to Co ⁶⁰ g-irradiation on a GUBE-3000 apparatus at a dose rate of 1.45 Gy / min.

 The first and second groups of 20 animals 30 minutes prior to irradiation were administered a sublingually-claimed composition comprising cysteine or cystine, respectively, at a dose of 6 mg / kg; the third and fourth groups of 20 animals were similarly administered glutathione in doses of 6 and 100 mg / kg, respectively; a control group of 20 animals was injected with an appropriate volume of distilled water. The survival and life span of the animals was evaluated within 30 days after irradiation. The results of the study are presented in the drawing and in table. 5.

 To study the radioprotective effect of the claimed composition at the molecular level in the first and control groups of animals before and on the fourth day after irradiation in peripheral blood lymphocytes, the activity of succinate dehydrogenase (Arch. Anat. Gistol. Embriol. 1969, v.5, p. 85) and succinate were measured β-cytochrome C-oxidoreductase (Nature, 1960, v. 187, p. 85; Proc. of the 8th Congress of the European Society of Haematology, Wien, 1961). The results of the study are presented in table. 6.

 The data table. 5 show that at a dose of 10 Gy, which is lethal for 100% of the control animals, the introduction of the claimed composition, including cysteine, leads to 35% survival and increases the average life expectancy to 10.2 days against 7.1 days in the control, time as the claimed composition, including cystine, determines 30% survival and increases the average life expectancy of up to 9.6 days. It should be noted that glutathione at a dose of 6 mg / kg of mass does not have a protective effect, and its administration at a dose of 100 mg / kg of mass causes only 10% survival and practically does not increase the life expectancy of animals.

 The survival curves of rats shown in the drawing show that the dynamics of death of control animals exhibits two peaks of mortality (curve 1), while the protective effect of the claimed composition, including both cysteine (curve 5) and cystine (curve 4), not only eliminates the second peak of mortality, but also shifts the first in time at the time of the appearance of the second peak in control animals.

 Glutathione at a dose of 6 mg / kg of mass does not cause any changes in the dynamics of death of rats compared with control animals (curve 2), while its dose of 100 mg / kg of mass only slightly increases the resistance of animals to radiation exposure (curve 3 )

 The radioprotective effect of the claimed composition, shown in radiobiological experiments on animal survival, is confirmed by cytochemical studies of the activity of respiratory chain enzymes (Table 6).

 As can be seen from the table. 6, the activity of both enzymes in control animals after irradiation is significantly increased compared with intact, while the introduction of the claimed composition leads to its preservation in experimental animals at the same level. Obviously, the claimed composition modifies radiation damage, significantly reducing radiobiological effects, which is accompanied by a decrease in the level of energy-consuming processes, such as DNA repair, protein synthesis, active ion transport, as a result of which the activity of the respiratory chain enzymes in the post-radiation period is practically unchanged and can serve as a promising test for assessment of the severity of radiation damage.

 The radioprotective effect of the claimed composition on the embryogenesis of white rats was studied.

The first group of 15 and the second group of 16 pregnant females, respectively, were administered the sublingually claimed composition, comprising cysteine, at a dose of 6 mg / kg of weight once a day during the period of active organogenesis from the 7th to the 10th day of pregnancy; the third and fourth groups of 15 pregnant females were similarly injected with glutathione at a dose of 100 mg / kg; the control group of animals from 14 pregnant females was similarly injected with an appropriate volume of water. The second, fourth and control groups of animals on the 10th day of pregnancy (after the course of administration of the corresponding preparations) were irradiated with a GUT- ⁶⁰ Co-400 unit at a dose of 2 Gy; the absorbed radiation dose rate was 0.13 Gy / min. On the 20th day of pregnancy, all groups of animals were euthanized, fetuses were extracted, the number of yellow corpuscles of pregnancy and implantation sites, the number of live and dead fetuses were calculated, and the relative death of the embryos before and after implantation was calculated. The fruits were weighed, their craniocaudal size was determined, and examined macroanatomically and microanatomically according to the Wilson method. Static processing was carried out using litter as an observation unit. For statistical processing, the Student criterion and the "and" Wilcoxon-Mann-Whitney criteria were used.

 The results of the study are presented in table. 7 and 8. These tables show that a preliminary four-fold administration of the claimed composition to pregnant rats significantly reduces the teratogenic effect of radiation exposure, significantly reducing the number of fetuses with developmental abnormalities and the severity of brain damage. Glutathione has a similar radioprotective effect only in a dose almost 20 times higher than that of the claimed composition. Moreover, the claimed composition in the used dose does not have an embryotoxic effect.

 The results obtained allow us to attribute the claimed composition to medium-effective radioprotectors, and its maximum protective effect is observed when cysteine is used as a sulfur-containing ingredient. Of particular interest is the extremely low dose of the claimed composition, which ensures the complete absence of toxic effect.

 The antihypoxic effect of the claimed composition was studied on pregnant female white rats weighing 250-300 g and their offspring.

A study of the effect of the claimed composition on the functional and metabolic state of the myocardium under hypoxia was carried out on a model of perfused heart of pregnant rats. The first group of 12 animals from 1 to 19 days of pregnancy once a day under the root of the tongue sublingually introduced the claimed composition, including cysteine, at a dose of 6 mg / kg; the second group of 12 animals and the third group of 6 animals from 16 to 19 days of gestation were similarly injected with the same claimed composition at a dose of 6 mg / kg weight and glutathione at a dose of 15 mg / kg weight, respectively; the control group of 12 animals from 16 to 19 days of gestation was similarly injected with the corresponding volume of water. On the 20th day of pregnancy, the rats were euthanized, their heart was removed and perfused according to Langendorff. The perfusion solution was oxygenated with normoxic (95% O ₂ + 5% CO ₂ ) and hypoxic (20% O ₂ + 75% N ₂ + 5% CO ₂ ) gas mixtures. The hypoxic state was modeled after stabilization of the studied physiological parameters of the heart (approximately 30 minutes after the start of perfusion). This moment was taken as the zero reference point and the heart rate and strength were recorded. The magnitude of the “work” performed by the heart was calculated as the product of the frequency and strength of the heart beat. The oxygen consumption rate of the perfused heart was determined polarographically. The data obtained are presented in table. 9.

 The data table. 9 show that the claimed composition has a high antihypoxic activity, significantly superior to that of glutathione. The level of "work" of the heart during hypoxia in animals of groups I and II is significantly higher than in controls, and similar indicators in animals of group II are significantly higher than those in animals of group III. Since the "work" of the heart is an integrative indicator that reflects the degree of myocardial energy, its increase under the influence of the claimed composition characterizes the energy effect of the latter. However, the indicated effect of the claimed composition, unlike the action of the known antihypoxants, is not accompanied by an increase in oxygen consumption by the hypoxic myocardium, which indicates an increase in the efficiency of ATP synthesizing systems due to an increase in the P / O ratio.

 The mechanism of antihypoxic action of the claimed composition, apparently, is to reduce the hyperreduction of the initial portion of the respiratory chain induced by the endogenous glutathione induced by it and thereby restore the ability to form ATP in the first oxidative phosphorylation point. In this case, the electron flow from the initial portion of the respiratory chain is not directed to its terminal sections, but is used in reactions specific for glutathione, such as peroxidase or glutathione-S-transferase reactions of reduction of hydroperoxides, the content of which increases with hypoxia. It should be noted that the antihypoxic effect of the claimed composition is most pronounced when it is administered from the 16th to the 19th day of pregnancy, since this is the period when the mother’s body has minimal protection from hypoxic effects, and the fetal body undergoes metabolic rearrangements and induction of enzymes necessary for childbirth and early postnatal development, then the likelihood of hypoxic exposure is maximum.

 Thus, the use of the claimed composition as an antihypoxic drug is most appropriate and effective at a time when the body is most susceptible and sensitive to hypoxic factor.

 The effect of the claimed composition on the individual resistance to hypoxia of the offspring of rats by introducing it to pregnant females was studied. The first experimental group of 6 animals from 16 to 19 days of pregnancy once a day on the root of the tongue sublingually introduced the claimed composition, including cysteine, at a dose of 6 mg / kg; the second experimental group of 6 animals was similarly injected with glutathione at a dose of 15 mg / kg; a control group of 6 animals was similarly injected with an appropriate volume of water. The individual resistance of the offspring of the experimental and control groups of rats to acute hypoxic hypoxia in males and females was determined by the pressure chamber method. The animals were placed in the supply and exhaust pressure chamber and the rise to a "height" of 11,000 m was simulated. The time from the moment of reaching the indicated "height" to the appearance of a second agonal inhalation in rats, the so-called standby time (RV), which is the criterion of the body's resistance to hypoxia, was measured. The data obtained are presented in table. ten.

 As can be seen from the table. 10, newborn animals of the control groups have increased resistance to hypoxia, which persists for the entire period of feeding (from 1 to 16 days). During weaning (from 16 to 30 days), a significant decrease in the resistance of rats to hypoxia occurs, which is manifested in a sharp decrease in RV. This phenomenon is explained by the increasing dependence of energy metabolism on the oxidation of carbohydrates and the associated relative physiological instability of the body.

 The introduction of the claimed composition to pregnant female rats leads to significantly higher than in control animals, the resistance of the offspring to acute hypoxic hypoxia. Young animals even during a period of relative physiological instability (from 16 to 30 days) show a high level of resistance to hypoxia. It should be noted that glutathione has a similar effect only at a dose 2.5 times higher than that of the claimed composition.

 The data obtained indicate that the claimed composition, administered to the female in the last third of pregnancy, stimulates both her and the fetus to develop adaptive-compensatory mechanisms that increase resistance to hypoxia. At the same time, protective mechanisms continue to work actively in the postpartum period, especially during periods of perinatal and near postnatal development.

 Thus, the claimed composition can be used both as a therapeutic and prophylactic antihypoxant of energetic action.

LD _{50 of the} claimed composition is determined in mice (a group of 50 animals weighing 25-30 g) and rats (a group of 30 animals weighing 200-250 g). It was found that with intragastric administration of LD _{50 of the} claimed composition, comprising cysteine or cystine, or methionine, is more than 3000 mg / kg of animal weight, therefore, the claimed composition is not toxic.

 A pathomorphological study of the internal organs of animals after repeated intragastric administration of the claimed composition, including cysteine or cystine, or methionine, for 60 days in doses up to 200 mg / kg of the animal’s weight did not reveal their morphological and pathological changes.

 The inventive composition was tested on 45 volunteer people suffering from chronic alcoholism and chronic coronary heart disease.

 The antitoxic effect of the claimed composition was studied in 30 sick men aged 20 to 25 years, suffering from chronic alcoholism of the I-II stage (duration of alcohol consumption from 5 to 20 years). In 12 patients, alcohol consumption was pseudo-binges, in 8 true binges. All patients were observed during the period of pronounced manifestations of alcohol withdrawal syndrome. Clinically, patients with vegetative-asthenic disorders (sweating, tachycardia, dry mouth) and neurological symptoms (tremor of the fingers, increased tendon reflexes, inaccurate movements, etc.) with sleep disturbance were observed. Patients in the control group (10 patients) received detoxification therapy with the use of B vitamins. Patients in the experimental group (20 patients) along with vitamin therapy took the claimed composition, including cystine, at a dose of 6 mg / kg of body weight sublingually 3 times a day for a week.

 The study showed that already 20-30 minutes after taking the claimed composition, the patients clearly felt its positive effect. Thus, a subjectively experienced group of patients noted stress relief and the occurrence of relaxation. Objectively, at the same time, a decrease and even disappearance (in 11 of 20 patients) of tremor of the fingers, a decrease in heart rate (from 94-98 to 82-88 beats / min) was observed.

 Reception of the claimed composition within 7 days showed that the patients of the experimental group already on the 2nd day started to sleep, tremor disappeared, and on the 3rd day and tachycardia. Subjectively, patients noted a sense of vitality and reassurance. In patients of the control group, tachycardia, tremor and sleep disturbance were observed up to 6-7 days of the experiment inclusive.

 The antihypoxic effect of the claimed composition was studied in 15 patients (8 women and 7 men) aged 60 to 72 years old, suffering from chronic coronary heart disease with circulatory disorders of the I-II degree with a disease duration of 1 to 3 years. Five patients had a history of myocardial infarction. All patients had symptoms of angina pectoris, and on the ECG, myocardial dystrophy and sinus tachycardia.

 The whole group of patients took a once sublingually claimed composition, including cysteine, at a dose of 6 mg / kg; on the second day, the same patients took the same composition as claimed, including cystine, at a dose of 6 mg / kg; on the third day, patients received similarly glutamic acid at a dose of 3 mg / kg; on the fourth day, patients received similarly glutathione at a dose of 6 mg / kg of body weight, and on the fifth, the claimed composition, comprising cysteine, at a dose of 6 mg / kg of body weight in gelatin capsules intragastrically. Before and 30 minutes after taking the above drugs, heart rate was measured in patients. The data of the same patients who received similarly sucrose at a dose of 6 mg / kg of the mass served as a control. The results are presented in table. eleven.

 As can be seen from the table. 11, the claimed composition, including both cysteine and cystine, when sublingually administered exhibits a significant antihypoxic effect, reducing the heart rate in patients. In addition, subjectively, patients felt a release of heaviness in the region of the heart.

 It should be noted that with the introduction of the intragastrically claimed composition, the latter loses its antihypoxic properties, which indicates a regular mechanism of its action.

 The administration of the tripeptide directly does not affect the heart rate, and one of its precursors, glutamic acid, in addition to the pulse rate in all patients, caused extrasystole in five of them lasting 40-90 minutes, and in four heart pains.

 Thus, the results of laboratory and clinical studies have shown that the claimed composition, in contrast to glutathione and its predecessors, induces a glutathione-conjugating system and has a pronounced anti-toxic, antihypoxic and radioprotective effect.

 The inventive composition is completely safe and has no contraindications.

Claims (8)

 1. A pharmaceutical composition that induces the biosynthesis of glutathione, the activity of glutathione transferase and has an antitoxic, radioprotective and antihypoxic effect, for sublingual administration, characterized in that as an active substance it contains an effective amount of a mixture of L-glutamic acid, glycine and a sulfur-containing amino acid selected including cysteine, cystine and methionine, or a mixture of pharmaceutically acceptable salts of these amino acids in a mass ratio of components 1 1 1 and also contains a pharmaceutically acceptable carrier.  2. The composition according to claim 1 in the form of a solution, powder or tablets, characterized in that it contains each of these components in an amount of 0.1 to 0.2 g per dose.  3. The composition according to claim 2, characterized in that it contains water or methyl cellulose as a pharmaceutically acceptable carrier.  4. A method for the prevention and treatment of chronic alcoholism and alcohol withdrawal syndrome by administering a medicament containing an amino acid, characterized in that as a medicament containing an amino acid, a sublingual pharmaceutical composition according to claim 1 is administered at a dose of 6 mg / kg weight 3 times day  5. A method for the prevention of intoxication with aromatic hydrocarbons or their derivatives in warm-blooded animals by administering a drug, characterized in that 30 minutes before exposure to a toxic agent, the pharmaceutical composition according to claim 1 is administered sublingually at a dose of 6 mg / kg weight.  6. A method of protecting against radiation damage to warm-blooded animals by administering a drug containing an amino acid, characterized in that 30 minutes before the start of radiation exposure as a drug containing an amino acid, the pharmaceutical composition according to claim 1 is administered sublingually at a dose of 6 mg / kg of weight.  7. A method of protecting against radiation damage to the offspring of warm-blooded animals by administering a drug containing an amino acid, characterized in that the females during pregnancy prior to radiation exposure as a drug containing amino acid, are administered sublingually the pharmaceutical composition according to claim 1 at a dose of 6 mg / kg of weight 1 time per day from the 7th to the 10th day of pregnancy.  8. A method for the prevention and treatment of hypoxic conditions by sublingual administration of a drug, characterized in that the pharmaceutical composition according to claim 1 is administered as a medicine at a dose of 6 mg / kg weight once a day.

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