RU2408232C1 - Biologically active food supplement with antidepressant effect and its production method - Google Patents

Abstract

FIELD: food industry. ^ SUBSTANCE: invention is related to phytotherapy. The biologically active supplement possessing antidepressant effect contains L-tryptophan, linseed-oil and vegetal components. The vegetal components are represented by oil extract of mother-of-thyme herb, common origanum herb, St.-John's wort herb, sandy everlasting blossom, common valerian root with rhizomes and elecampane root with rhizomes taken in a ratio of 0.8-1.2:0.8-1.2:0.8-1.2:0.8-1.2:0.8-1.2:0.8-1.2 accordingly and a dried water extract produced by way of expression of the same components after oil extraction. The biologically active supplement production method envisages mixture of the above components. The oil extract is produced by extracting the vegetal raw material with vegetable oil at a temperature of 50-70C during 5-10 h with subsequent separation of the raw material. The water extract is produced by extracting the raw material, expressed after oil extraction, with water at a temperature of 50-70C during 5-10 h with subsequent filtrate filtering and drying to produce the dry solid. ^ EFFECT: invention enables production of a supplement that is efficient in therapy of different forms of stress including sleep disturbance with patients of different age groups, aggressiveness, instability of temper, state of anxiety, has a positive effect on normalisation of the brain electrical activity indices and basic brain blood circulation indices and possessing antioxidant action. ^ 9 cl, 4 tbl, 1 ex

Description

The invention relates to medicine, in particular to herbal medicine and parapharmaceutical industry, producing drugs for therapeutic and prophylactic purposes, and can be used in a state of chronic stress to eliminate its symptoms - various forms of sleep disturbance, aggressiveness, mood instability, depression, high fatigue, irritability , anxiety, difficulty concentrating. Stress is a nonspecific reaction of the body to a situation that requires more or less functional restructuring of the body, appropriate adaptation. In the age of urbanization, computers, cars, stressful situations began to haunt people more and more. According to the American Psychological Association (ARA), 32% of US residents experience severe nervous tension, and 77% of Americans live constantly in conditions of chronic stress, experiencing symptoms such as irritability, anger, nervousness, sleep disorders. Social tension affects sleep 48% of people, 43% are saved from stress by gluttony, 78% of the Americans surveyed believe that only a doctor can help them in stressful situations. The clinical symptoms for stress are quite diverse: a sensation of pain in the back of the head or behind the sternum, severe insomnia, shortness of breath, high blood pressure (BP), tiredness, physical and mental exhaustion, difficulty concentrating, distraction, and sometimes depression of varying severity. It has been shown that the triggering mechanism of most cardiovascular diseases is a series of stressful situations (pathological stress) or psychoemotional stress syndrome, which lead to a number of completely different diseases. The subsequent condition for the deepening of stress leads, as a rule, to the formation of distinct pathophysiological changes in the body, which can develop according to various scenarios from initial reversible disorders to severe somatic diseases such as stroke or myocardial infarction. One of the most pronounced and vivid manifestations of stress are various forms of sleep disturbance. Official medicine in the treatment of sleep disorders uses quite toxic groups of drugs belonging to the group of sleeping pills. These include barbiturates, small and large tranquilizers, synthetic antidepressants, such as iproniazide, which became the ancestor of the group of antidepressants - MAO inhibitors (monoamine oxidases), and imipramine, on the basis of which tricyclic antidepressants are obtained. The reference antidepressant, which is widely used to treat depression, is amitriptyline (5- (3-dimethylaminopropylidene) -10, 11-dihydrodibenzocycloheptin hydrochloride (Mashkovsky M.D. Medicines // Pharmacotherapy Manual for Doctors Part 1, M .: Medicine - 1988, pp. 90-96). The disadvantages of amitriptyline as a reference preparation are the presence of a sedative and pronounced anticholinergic effects, the relatively slow onset of the therapeutic effect, as well as a direct dose-dependent effect, requiring constant gradually dose increase during course use and gradual dose reduction when drug is discontinued, professional activities requiring attention and speed of making right decisions are limited.The use of most chemically synthesized antidepressants leads to undesirable consequences such as drowsiness, lethargy, decreased working capacity and reaction rate, drug A successful alternative to such drugs is the essential amino acid L-tryptophan. The known drug tryptophan - Vita-Tryptophan, available in capsules of 230 mg (Sanitary and epidemiological conclusion No. 77.99.23.3. U.9631.11.08, 2008-11-14 from Westline (Russia); manufacturer: Nittany Pharmaceuticals Inc. (USA) (http://rlsnet.ru/tn_index_id_29839.htm). Vita-Tryptophan is recommended for the synthesis of serotonin, one of the most important neurotransmitters in the brain; participates in the production of niacin (vitamin B3); is necessary to increase the release of growth hormone; improves mood, reduces a sense of fear and tension, eliminates dysphoria, reduces anxiety; improves sleep, relieves depressive states, however, this preparation is 5-hydroxytryptophan (from Griffonia griffonia simplicifolia), which is a derivative of the amino acid L-tryptophan. In addition, the plant Griffonia simplicifolia grows in central and western Africa

(http://en.wikipedia.org/wiki/Griffonia_simplicifolia) and as raw materials in Russia is inaccessible. Also known is the biologically active dietary supplement 5-HTP Power (5-hydroxytryptophan) (Nature's Sunshine Products, Certificate of State Registration 77.99.23.3. U.8022.8.06), containing 1 capsule: 5-hydroxytryptophan - 35 mg; Siberian ginseng root (Eleutherococcus senticosus) - 286.2 mg; Sumy root (Pfaffia palculata) - 50 mg; Ashwagandha root (Withania somnefera) - 50 mg; pyridoxine hydrochloride (vitamin B6) - 3 mg; zinc (gluconate) - 3 mg. This drug is recommended for improving sleep, has an antidepressant effect, relieves nervous tension, eliminates anxiety and reduces appetite. However, this drug also contains 5-hydroxytryptophan and plants, known as powerful stimulants of the nervous system, which are contraindicated in patients with hypertensive vegetative-vascular dystonia. The main task to which the invention is directed is to expand the spectrum of biologically active additives with antidepressant action and containing natural components. Another objective is to increase the effectiveness of a tryptophan-based drug. The tasks are solved by the fact that a biologically active additive having an antidepressant effect is proposed, including tryptophan and plant components, which, according to the invention, additionally contains linseed oil, and as plant components an oil extract from creeping thyme grass, common oregano grass, St. John's wort grass , flowers of an immortelle sand, root with rhizomes of Valerian officinalis and root with rhizomes of Elecampane high, taken in the ratio, parts: 0.8-1.2: 0.8-1.2: 0.8-1.2: 0, 8-1.2: 0.8-1.2: 0.8-1.2 respectively . Governmental dried aqueous extract obtained from extraction of said vegetable raw material after extraction of the oil, with the ratio of components, wt%:

Tryptophan 4.0-8.0 Oil extract 5.0-50.0 Dried water extract 0.25-1.5 Linseed oil Up to 100

Moreover, the additive contains L-tryptophan as tryptophan. The additive also contains a dry aqueous extract in an amount of at least 0.5 mg / ml and active ingredients: valerenic acid in an amount of at least 0.0075 mg / ml, vitamin E - at least 0.5 mg / ml, γ- tocopherol - at least 0.04 mg / ml, lycopene - at least 0.001 mg / ml, β-cryptoxanthin - at least 0.01 mg / ml, α-carotene - at least 0.03 mg / ml, β-carotene - at least 0.004 mg / ml, polyunsaturated fatty acids not less than 500 mg / ml, including Omega-3 - not less than 300 mg / ml and Omega-6 - not less than 200 mg / ml. The oil extract includes at least one component selected from the group consisting of olive, soybean, rapeseed, linseed and sunflower oil. The dietary supplement can be prepared in the form of an elixir or capsules, for example, from gelatin. The tasks are also solved by the fact that a method for producing a biologically active additive having an antidepressant effect, comprising mixing tryptophan with plant components, in which, according to the invention, is first carried out the extraction of plant materials with vegetable oil at a temperature of 50-70 ° C for 5-10 hours, followed by separation of the raw materials, then the extracted raw materials are extracted with water at a temperature of 50-70 ° C for 5-10 hours, followed by filtration and drying of the filtrate to a dry residue, floor chennye extracts were combined, tryptophan introduced and mixed with the linseed oil. At the same time, creeping thyme grass, common oregano grass, St. John's wort grass, sandwort immortelle flowers, root with rhizomes of Valerian officinalis and root with rhizomes of elecampane are taken as plant raw materials in the ratio, parts: 0.8-1.2: 0.8 -1.2: 0.8-1.2: 0.8-1.2: 0.8-1.2: 0.8-1.2, respectively. As tryptophan take L-tryptophan. Flaxseed oil or a mixture of linseed oil with another vegetable oil selected from the group consisting of olive, soy, rapeseed and sunflower oil is taken as an extractant. Preferably, the plant material and extraction oil are taken in a ratio of 1: 0.5-20. The oil extract is separated by pressing the raw material under pressure. Pressed raw materials are poured with water in a ratio of 1: 2-4. Drying of the aqueous extract is carried out by removing water with a vacuum apparatus at a temperature of 50-60 ° C and a vacuum of 600-650 mm Hg The resulting preparation of biologically active additives can be packaged in capsules, which can be prepared from gelatin. Thus, the technical result achieved by the invention is to obtain a drug having an antidepressant effect and containing oil and water extracts from plant materials of a certain composition and a certain amount of edible flaxseed oil, including a dry aqueous extract of at least 2.5 mg / ml , valerenic acid in an amount of at least 0.0075 mg / ml, vitamin E - at least 0.5 mg / ml, γ-tocopherol - at least 0.04 mg / ml, lycopene - at least 0.001 mg / ml, β-cryptoxanthin - at least 0.01 mg / ml, α-carotene - at least 0.03 mg / ml, β-carotene - at least 0.004 mg / ml, L - tryptophan 40-60 mg / ml, polyunsaturated fatty acids not less than 500 mg / ml, including Omega-3 - not less than 300 mg / ml and Omega-6 - not less than 200 mg / ml, but not more physiologically acceptable for humans. Another technical result is that the proposed composition is more physiological for older people compared to pure L-tryptophan and does not contain potent substances that are contained, in particular, in the root of ginseng Eleutherococcus senticosus. Clinical trials of the drug of the proposed biologically active additives (BAA), conducted at the Izhevsk State Medical Academy (IGMA) and at the Department of Hospital Therapy of IGMA, showed that this supplement is a highly effective tool in combating various types of stress and how its manifestation of sleep disturbance in patients of various age groups. In addition, the effect of normalizing the level of cholesterol and its derivatives was confirmed, the positive effect of the additive on the normalization of the indicators of electrical activity of the brain according to EEG was proved. It was found that with the course use of the supplement, the main indicators of cerebral circulation are normalized. The proposed additive has antioxidant activity, increasing the content of endogenous antioxidants in the body, and according to biopolymer exchange markers (PSO), it enhances the synthesis of oxyproline in the brain tissue. For the manufacture of the drug take well-known medicinal plants. Hypericum perforatum - Hypericum perforatum (State Pharmacopoeia XI Art. 52 p. 323), the herb of which contains tannins, pyrocatechin derivatives, essential oils, flavonoids (hyperoside, rutin, quercetin, isoquercetin, quercetrin), azulene, coloring matter: hyperecin, pseudohyperepine hypericodehydrodiantrone, pseudohypericodehydrodiandrone, franguloemodinantrocol, carotene, ceryl alcohol, choline, vitamins C, PP, anthocyanins, saponins, resinous substances. The active substances of St. John's wort have an astringent, bactericidal, anti-inflammatory, biostimulating and pronounced choleretic effect. The roots and rhizomes of Valerian officinalis are Valeriana officinalis L. (GF XI Art. 77 p. 369), which contain essential oil, hydrocarbons, alcohols, aldehydes, acids, ketones, esters, glycosides, carbohydrates, tannins, alkoloids (valerin and hatinin). Preparations from the roots and rhizomes of valerian have a calming and antiemetic effect. Origanum ordinary - Origanum vulgare (L. GF XI Art. 55 p. 328), in the grass of which ascorbic acid, pigments, flavonoids, tannins, as well as essential oil containing phonols (thymol, carvacrol), bicyclic and tricyclic terpenes, sesquiterpenes, free alcohols and geranyl acetate. The active substances of oregano have a calming effect, have antiseptic properties. Sand immortelle flowers - Helichrysum arenarium (L.) Moench. (GF XI Art. 9 p. 244), which contain flavonoids, tannins (tannin), coumarins, saponin, resin, beta-phytosterol and other similar compounds. Immortelle preparations accelerate blood coagulation, have choleretic and anthelmintic effects. The roots and rhizomes of elecampane high - Inula helenium. L. (GF XI Article 73 p. 366), containing essential oils, inulin and other polysaccharides, stigmasterol, bitter substances, pseudoinulin, acetic and benzoic acids, tocopherols, saponins, resins, gum, mucus, pigment and a small amount have not yet identified alkaloids. Essential oils contain a mixture of sesquiterpene lactones - alantolactone, iso-alantolactone, dihydroalantolactone and alantholic acid, proazulene. Elecampane preparations have bactericidal and anti-inflammatory properties, reduce intestinal motility, reduce the activity of phosphatase, enterokinase and lipase enzymes. Creeping thyme grass - Thymus serpyllium L. (GF XI Art. 60 p. 338), containing essential oil, tannins and tarry substances, saponins and flavonoids. Thyme herb preparations have antiseptic and disinfectant effects. L-tryptophan is an amino acid for parenteral nutrition, CGR No. 77.99.26.9. U.4558.6.07 of 06/26/2007. To obtain the extract from plant materials, they take linseed edible oil (TU 9141-003-49340753-08) and vegetable oil selected from the group comprising olive (FS 421776-92), soybean, rapeseed (GOST 8988-77) and sunflower (GOST 1129-93) oil. The essence of the invention lies in the fact that the composition and ratio of plant components, the composition of the extractants and the conditions for obtaining the extract into which L-tryptophan is introduced is selected, and thus a dietary supplement is obtained, experimental verification of which showed that it can be used as an antidepressant - a highly effective means in the fight against different types of stress and how its manifestation is sleep disturbance in patients of different age groups. The invention is illustrated by the following examples of specific performance.

EXAMPLE 1

To obtain the proposed dietary supplement preparation, they took (in) 5.0 St. John's wort herbs, 5.0 creeping thyme herbs, 5.0 common oregano herbs, 5.0 flowers of sandy immortelle, 5.0 rhizomes and root of elecampane high, 5.0 rhizomes and root of Valerian officinalis, 30.0 L-tryptophan, 17.2 olive oil and 450.0 edible flaxseed oil. The plant material was loaded into a container with a water jacket, olive oil and about half of linseed oil were added and kept at a temperature of 60 ° C for 7 hours. The resulting extract was poured and squeezed under pressure. Water was added to the squeezed raw material in a ratio of 1: 3 by volume and kept at a temperature of 60 ° C for 6 hours, then filtered. The liquid from the filtrate was distilled off under a vacuum apparatus at a temperature of 60 ° C and a vacuum of 600-650 mm Hg. to a dry extract, which was obtained in an amount of 5.0 g. An oil extract was obtained 197 g. The dry extract was combined with an oil extract, the remaining linseed oil, L-tryptophan was added, stirred, if necessary, the resulting mixture was brought to a total weight of 500.0 g adding linseed oil and sent to packaging, where on a capsule machine filled with the finished preparation gelatin capsules in an amount of 1000 pcs. The content of antioxidants in the finished product was determined by high performance liquid chromatography. The resulting preparation contains a dry aqueous extract in an amount of 10.0 mg / ml and active ingredients: valerenic acid in an amount of 0.008 mg / ml, vitamin E - 0.55 mg / ml, γ-tocopherol - 0.04 mg / ml, lycopene - 0.001 mg / ml, β-cryptoxanthin - 0.015 mg / ml, α-carotene - 0.03 mg / ml, β-carotene - 0.004 mg / ml, L-tryptophan 60.0 mg / ml, polyunsaturated fatty acids 500 mg / ml, including Omega-3 - 300 mg / ml and Omega-6 - 200 mg / ml. Tests of the drug were carried out at the Izhevsk State Medical Academy, in a number of leading clinics of the Udmurt Republic and at the Department of Hospital Therapy of IGMA. Comprehensive clinical, instrumental and biochemical studies were conducted in 45 patients, including in the main group, 1-30 middle-aged people (67.3 ± 5.5 years), of which 18 men and 12 women; in the control control group, 15 people aged 65.6 ± 2.0 years were examined, including 10 men and 5 women. Both groups did not differ significantly by gender and age. All patients of the main and control groups had a history of the following disease structure: 96% - arterial hypertension; 72% - arterial hypertension complicated by encephalopathy; 48% - confirmed osteochondrosis of the cervical spine; 26% - severe cerebral arteriosclerosis and coronary heart disease (CHD), heart failure (HF) of 1-11 degrees; 10% - consequences of traumatic brain injury; 12% - the consequences of acute cerebrovascular accident (stroke). Almost all patients complained of frequent headaches, poor sleep, irritability. All patients of the main group took the drug (BAA) in a dose of 2 capsules 3 times a day, with the following content of components per 1 capsule weighing 0.5 g: L-tryptophan - 30 mg, oil extract from plant material - 40 mg, dry water extract from plant materials - 5 mg, linseed oil - 425 mg. Analysis of the drug was carried out on the basis of clinical, laboratory and instrumental data. A number of clinical symptoms (irritability, impulsivity, difficulty concentrating, anxiety, insomnia, poor sleep, headaches, premenstrual syndrome, drowsiness) in each subject were evaluated depending on the severity of the symptom using a 4-point system: 0 - no symptom or its disappearance ; +1 - a slight improvement; +2 - moderate improvement; +3 - marked improvement. Studies of systolic and diastolic blood pressure were performed by the oscillographic method using an OMRON RX-3 (HEM-640-E) model of automatic blood pressure measurement. Regional cerebral circulation was studied by rheoencephalography (REG) on a multichannel impedance plethysmograph with a quantitative and qualitative assessment of cerebrovascular resistance (MSS), pulse blood filling (PC). The reactivity of the vascular wall (RCC) to the saturation of carbon dioxide in the vascular bed was determined by a breathing test. Of the biochemical research methods, we used the determination of total cholesterol, LDL (low density lipids) and HDL (high density lipids), which was carried out in the biochemical laboratory of the City Hospital No. 8 of Izhevsk on a semi-automatic photometric analyzer SP 901-M made in Finland using diagnostic kits of the company Cormay. Diagnostic kits Cormay Chol Lts, Cormay Chol 60 Lts, Cormay Chol 120 Lts were used to determine total cholesterol. The standard risk of hypercholesterolemia occurs when its concentration is 5.2-6.8 mmol / L. High risk - more than 6.8 mmol / L. The standard values of total cholesterol are 3.1-5.2 mmol / L. To determine α-cholesterol, the Lab System diagnostic kit, HDL-Cholesteril, Precipitating Reagent manufactured in Finland was used. α-cholesterol is a high density lipoprotein (HDL), which helps reduce the risk of atherosclerosis and obesity. HDL protects blood vessels because they transfer cholesterol from peripheral tissues during its excretion. Serum β-lipoproteins were determined by the turbidimetric method according to Burstein and Samai. β-lipoproteins are low density lipoproteins (LDL). LDL is responsible for the transport of cholesterol into cells. The antioxidant content in the body was measured using Romanov spectroscopy on an American biophoton scanner using a non-invasive method. The KIC indicator - the level of oxidative stress was determined on a color scale with gradations from 10 to 50 thousand KIC units. The statistical processing of the material was carried out on an IBM computer in a semi-automatic mode using the standard MS Excel 2003 software package for small samples by Student and Fisher methods with an estimate of the probability of an erroneous conclusion with a gradation of 5 and 1%. Together with the average value (M), its error (m) is indicated, separated by the “□” sign and the number of studies included in the analysis (n). Table 1 presents the data of the main clinical symptoms in patients of the main group.

Table 1 Symptoms Symptoms before treatment Symptoms after treatment Percent disappearance of symptoms after treatment Irritability 19 2 89 ± 7 Impulsiveness 12 3 82 ± 12 Difficulty concentrating 16 four 88 ± 8 Anxiety state 8 one 88 ± 12 Insomnia 12 3 82 ± 2 Bad dream 23 0 0 Frequent headaches fifteen 2 87 ± 9 Premenstrual syndrome 2 0 0 Drowsiness 0 one one

As can be seen from table 1, according to the main clinical symptoms of the proposed drug significantly improved the condition of patients during its course administration. Moreover, the overwhelming number of patients noted improvement after 5 days of taking the drug. In middle-aged patients, symptoms of irritability, anxiety, and difficulty concentrating prevailed. Thus, in the overwhelming number of patients after a course of taking the proposed drug, most of the symptoms presented by the study participants significantly disappeared. Patients noted improvement in mood, the disappearance of anxiety, irritability. The frequency of headaches significantly decreased after 6-8 days of taking the drug. Complaints of poor sleep were presented by 73 ± 8% of patients; after a course of taking the drug, sleep was normal in all patients. In 12 elderly patients who took regular sleeping pills, insomnia was observed, which is a manifestation of severe atherosclerosis of the cerebral vessels, in 75 ± 13%. 8 patients were transferred to taking the drug with normalization of sleep with a gradual dose reduction and the complete abolition of sleeping pills. Three patients at the same time as taking dietary supplements continued taking sleeping pills. In 2 patients, the manifestations of premenstrual syndrome disappeared; women have been harassed for more than a year. In 87 ± 9%, the frequency of headaches decreased already from the second week of dietary supplement intake, and starting from the 3rd week of course administration, not a single case of headaches was recorded. At the same time, stabilization of blood pressure was noted.

table 2 The results of neuropsychological testing in points in middle-aged patients (n = 17) Symptom Before taking dietary supplements After taking dietary supplements Credibility In 2 weeks In 3 weeks Degree of anxiety 2.01 ± 0.09 1.16 ± 0.06 0.9 ± 0.05 P <0.01 Degree of irritability 2.03 ± 0.1 1.3 ± 0.2 1.0 ± 0.1 P <0.01 Degree of attention 1.54 ± 0.16 1.1 ± 0.08 1.2 ± 0.02 P <0.01 Degree of sleep disturbance 2.2 ± 0.2 1,0 ± 0,0 0 P <0.01

Table 2 presents the results of the dynamics of neuropsychological testing after a 2- and 3-week course of taking dietary supplements in a dose of 2 capsules 3 times a day in patients of the middle age group. The table shows a significant decrease in all of these test indicators, and an increase in the duration of the course of administration enhances the effect of dietary supplements. At 2 and 3 weeks of the course dietary supplement administration, significant changes in the test were achieved with respect to the initial indicators. All patients, without exception, noted improvement in sleep, removal or reduction of anxiety, and mood improvement. The improvement in general condition and mood was accompanied by positive dynamics in the normalization of blood pressure. Despite the fact that all patients before taking dietary supplements regularly took antihypertensive drugs from the ACE inhibitor group and nevertheless noted instability of blood pressure and the inability to select the appropriate dose of antihypertensive therapy. Starting from the 3rd week of dietary supplement supplementation with antihypertensive therapy, positive significant dynamics of systolic blood pressure reduction was noted. A decrease in blood pressure of the diastolic component was noted starting from 4 weeks of illness. The overwhelming number of patients taking dietary supplements, along with a decrease in blood pressure, improved sleep, and mood stabilization, noted a decrease in headaches (table 1). In 2 middle-aged patients, the disappearance of premenstrual syndrome was recorded, between 2 and 3 weeks of taking dietary supplements, patients noted the disappearance of anxiety, irritability, aggressiveness, and pains in the lower abdomen did not appear, which, as a rule, have bothered women in recent years. All patients participating in the examination underwent dynamic testing in terms of fat metabolism, which is presented in table 3.

Table 3 Comparative dynamics of indicators of fat metabolism in patients of the main and control groups Mg /% The main n group n = 26 Control group n = 12 Before receiving 30 days Before receiving 30 days Total cholesterol 225 ± 4.1 186 ± 6.6 * 215 ± 11.0 213 ± 16.0 HDL 23 ± 11.2 43 ± 6.0 * 21 ± 9.2 19 ± 11.2 LDL 56 ± 9.2 24 ± 8.5 * 58 ± 10.1 54 ± 8.1 TG 113 ± 8.5 101 ± 2.5 * 113 ± 22.0 112 ± 24.0 * - reliability at the level within the group p <0.05

As can be seen from table 3, in patients of the main group receiving dietary supplements, a reliable positive dynamics of all indicators without exception was revealed, in contrast to the comparison group (control group). In order to assess the intensity of collagen metabolism in brain tissues, a study was carried out of the content of peptide-bound oxyproline (PSO). During metabolic processes that occur constantly in the body, time intervals of the rate of metabolic processes of protein metabolism of brain tissue were evaluated. The analysis of the content of oxyproline was carried out according to a modified method of P.N.Sharayev at the Department of Biochemistry, IGMA. It was found that in the control group the exchange of biopolymers proceeded for a month exactly without rises and kept at the level of 1.1-1.3 μg / ml, with some unreliable decrease to 0.8 μg / ml at the end of 4 weeks of the study. In the main group, a significant increase in the exchange of biopolymers between 10 and 15 days of taking the drug from 1.5 ± 0.3 μg / ml to 3.1 ± 0.8 μg / ml was noted. The rate of exchange of protein polymers remained high, starting from the 15th day of taking the drug, which probably indicates an acceleration of protein synthesis and collagen metabolism. A significant difference was noted in the level of intensity of the exchange of biopolymers between the main and control groups. The increase in the rate of oxyproline metabolism coincided in time with the improvement of the clinical condition of patients of the main group. Studies of hemodynamic parameters were performed using the rheoencephalography method. According to the REG data, in the main group, a significant (15 of 18), p <0.05) decrease in cerebral vascular resistance (MSS) was noted in 69 ± 9% (18 of 26) with an initial elevated level. At the same time, an increase in pulse blood supply (PC) was also noted. This indicator slightly increased only in the case of initially decreased below normal PC (in 8 out of 26 patients). In the case of normative values of hemodynamic parameters, the changes were insignificant and were not reliable. Comparison of the obtained results of the REG study and blood pressure indicators, as a rule, coincided with the clinical data of the improvement in overall health and the reduction or disappearance of headaches during the course of the proposed drug. Thus, the obtained REG data indicate a positive effect of dietary supplements on indicators of cerebral circulation. To study the indicators of brain electrical activity, a group of middle-aged patients (n = 10) with a diagnosis of arterial hypertension was specially allocated. All patients complained of frequent headaches, mood instability, short temper, frequent mood swings, high fatigue, and sleep disturbance. The severity of these symptoms increased dramatically after night shifts. All patients on duty were on daily duty without the right to sleep at night every 2 days. An attempt was made to record the EEG of the brain and REG in these patients before duty in the morning, and then after night duty also at the same time in the morning from 9.00 to 10.00. After the study, patients took the proposed dietary supplement for a month, continuing to go on night shifts with the same frequency. 25-30 days after the night watch, again in the morning hours the registration of EEG and REG was carried out. The results of these studies are shown in table 4.

Table 4 The dynamics of EEG indicators in patients of the compared groups Pathological symptoms of EEG Control n = 10 2 weeks after taking dietary supplements n = 10 Credibility Before duty After duty Before duty After duty The decrease in the amplitude of the α-rhythm to 8 comb / sec below 20 μV 2 8 one 2 P <0.05 20 ± 13% 80 ± 13% 10 ± 10% 20 ± 13% B-rhythm - low amplitude frequency 2 6 one 2 P <0.05 20 ± 13% 60 ± 16% 10 ± 10% 20 ± 13% The presence of half-way asymmetry 0 6 0 one P <0.05 60 ± 16% 10 ± 10% Δ rhythm 0 3 0 one 30 ± 15% 10 ± 10% Θ (theta) rhythm 0 2 0 0 20 ± 13%

Table 4 shows the pathological changes in the indicators of electrical activity of the brain in patients of the compared groups. In 80% of patients on duty without obvious signs of overwork, an α-rhythm was recorded with symmetry in both hemispheres with sinusoidal waves with an amplitude in the range of 45-60 μV. However, immediately after duty, the overwhelming majority of patients (8 out of 10) showed a decrease in the amplitude of the α rhythm by EEG, and a decrease in its frequency below 20 μV. Pronounced interhemispheric asymmetry appeared. In 6 patients, single episodes of the low-amplitude B-rhythm were recorded, 30% of the episodes of the Δ-rhythm were registered, in 2 patients, single waves of the Θ-rhythm appeared. These changes reflect a clear violation of the electrical activity of the brain, characteristic of patients with impaired functional ability of the brain and, in this case, interpret the manifestation of a deterioration in cerebral blood flow (vascular spasms, increased tone, etc.) obtained by a parallel study of REG data. After a three-week course of the proposed dietary supplement according to the EEG, 90% of patients recovered and the sinusoidal α-rhythm began to dominate with a frequency of 0.5 fps. Patients disappeared interhemispheric asymmetry. B-rhythm with single rare episodes is registered in one patient. One patient left an α-rhythm with a slightly reduced amplitude. After the duty, the EEG data in the main group were significantly better than in the control group (Table 4) and were reliable in three main parameters. In 20% of patients versus 80%, a slight coarse decrease in the amplitude of the α-rhythm to 20 μV was noted; the B-rhythm with periods of rare episodes was preserved in 20%. After 10% of duty, there was a slight interhemispheric asymmetry and rare episodes of the Δ-rhythm. Thus, the course of the proposed drug improves the readings of the electrical activity of the brain. The positive effect of dietary supplements is especially evident in stressful situations in the form of severe overwork. In elderly patients, the registration of EEG revealed more severe violations of the electrical activity of the brain. In 9 patients with a pronounced manifestation of atherosclerosis, a sharper decrease in the activity of the α-rhythm up to a flat EEG, the presence of longer episodes of the B-rhythm with the transition to the theta rhythm were noted. After a 30 day course of taking the proposed drug, a clinically significant improvement in the general condition was noted, so all 9 patients improved and normalized sleep indicators. Thus, the results of the study confirm the effectiveness of the use and application of the proposed drug in patients with various forms of manifestation of stress, and primarily with various forms of sleep disturbance in patients of different age groups. In patients of the middle age group, the proposed drug normalized sleep, the violation of which was a clear manifestation of stress, while dietary supplements suppressed aggressiveness, mood instability, anxiety and other symptoms of stress. In old age, disturbed sleep was often one of the symptoms of severe atherosclerosis, however, in this case, the proposed drug was an effective means of normalizing sleep. An important advantage of the action of therapy with the proposed drug is the absence of side effects. Supplements do not cause drowsiness or impaired response in the daytime. On the contrary, patients noted vigor, increased working capacity and good emotional mood in the daytime. A positive aspect of the effect of the proposed drug on the body is the increased content of endogenous antioxidants, which also protect the body from unfavorable stress conditions at the cellular level. Some stabilization and decrease in blood pressure due to the instability and instability of blood pressure when taking ACE inhibitors (angiotensin-converting enzyme inhibitors (http://old.consilium-medicum.com/media/refer/07_06/14.shtml) is also an important advantage of the action of dietary supplements. a significant decrease in fat metabolism. This component of the dietary supplement action is no less important than the above listed effects. Protection against atherosclerosis, a significant decrease in cholesterol and its derivatives during the course of the use of dietary supplements make the proposed drug essentially a universal remedy. the study of the indicators of the electrical activity of the brain and the improvement of the indicators of cerebral circulation are the result of the integrated action of all dietary supplement components aimed at reducing oxygen starvation of the brain under stress and overfatigue, increasing the metabolism of biopolymers in the brain tissues.Thus, the studies confirm that the proposed drug is a highly effective tool in the fight against different types of stress and, as its manifestation, sleep disturbance in patients of various age groups. In addition, the effect of normalizing the level of cholesterol and its derivatives was reliably confirmed, a positive effect on the normalization of the indicators of the electrical activity of the brain according to the EEG and the main indicators of cerebral circulation during course application was proved. The proposed drug has antioxidant activity, increasing the content of endogenous antioxidants in the body, and also, according to biopolymer exchange markers (PSO), enhances the synthesis of oxyproline in the brain tissue. It can be recommended to the general population experiencing a state of chronic stress and, as its manifestation, complaining of various forms of sleep disturbance, aggressiveness, mood instability, depression, high fatigue, irritability, anxiety, difficulty concentrating. The proposed drug is recommended in complex therapy for patients with severe atherosclerosis of the cerebral vessels, as well as for patients with a pathological manifestation of electrical brain excitability. These can be patients with hypertension complicated by encephalopathy up to patients with a stroke or myocardial infarction.

Claims (9)

1. A biologically active additive that has an antidepressant effect, including tryptophan and plant components, characterized in that it additionally contains linseed oil, and as plant components an oil extract from creeping thyme grass, common oregano grass, St. John's wort grass, sandwort flowers, sandwort root rhizomes of Valerian officinalis and root with rhizomes of Elecampane high, taken in the ratio, h: 0.8-1.2: 0.8-1.2: 0.8-1.2: 0.8-1.2: 0 8-1.2: 0.8-1.2, respectively, and dried aqueous extract obtained from annealing and the same vegetable oil component after extraction, with the ratio of components, wt.%:
Tryptophan 4.0-8.0 Oil extract 5.0-50.0 Dried water extract 0.25-1.5 Linseed oil up to 100 2. The dietary supplement according to claim 1, characterized in that it contains L-tryptophan as tryptophan. 3. The dietary supplement according to claim 1, characterized in that the oil extract is obtained by extraction with at least one vegetable oil selected from the group comprising olive, soy, rapeseed, linseed and sunflower oil. 4. The dietary supplement according to claim 1, characterized in that it is packaged in gelatin capsules. 5. A method of obtaining a biologically active additive having an antidepressant effect, including mixing tryptophan with plant components, characterized in that the oil and water extracts of creeping thyme grass, common oregano grass, St. John’s wort, St. John’s wort, sandwort flowers, root with rhizomes are taken as plant components Valerian officinalis and root with rhizomes of elecampane high in the ratio, h: 0.8-1.2: 0.8-1.2: 0.8-1.2: 0.8-1.2: 0.8- 1.2: 0.8-1.2, respectively, as well as linseed oil, and the oil extract according to teach extraction of plant materials with vegetable oil at a temperature of 50-70 ° C for 5-10 hours, followed by separation of the raw materials, and the aqueous extract is obtained by extraction of raw materials squeezed after oil extraction with water at a temperature of 50-70 ° C for 5-10 hours, followed by filtering and drying the filtrate to a dry residue. 6. The method according to claim 5, characterized in that as tryptophan take L-tryptophan. 7. The method according to claim 5, characterized in that the extractant is taken linseed oil or a mixture of linseed oil with at least one vegetable oil selected from the group comprising olive, soybean, rapeseed and sunflower oil. 8. The method according to claim 5, characterized in that said additive is packaged in capsules. 9. The method according to claim 8, characterized in that the capsules are prepared from gelatin.