RU2171113C1 - Elixir showing total tonic and adaptogenic action - Google Patents

Abstract

FIELD: medicine, phytotherapy. SUBSTANCE: invention relates to development of alcohol-containing complex preparation of natural origin based on vegetable raw. Elixir is an aqueous- -spirituous extract of Sibirian cedar pine seeds, Eleutherococcus senticosus rhizomes and roots, haw-thorn flowers and fruits, rowan melanocarpous (Aronia) fruits and birch buds and it has additionally honey, sugar syrup, 95%-th ethyl alcohol and water taken in the following ratio of components, g: an aqueous-spirituous extract. 550-600 ml; natural honey, 45-50; sugar syrup, 30-35; 95%-th ethyl alcohol, 100-110 ml; purified water, up to 1000 ml. An aqueous- -spirituous extract has substances to be oxidized as measured for tannin in the amount 85 mg/l, sum of flavonoids 14 mg/l. Tannin content in the end product is 50 mg/l and sum of flavonoids is 7 mg/l. Elixir intake results to the stable therapeutic effect in treatment of patients with atherosclerosis and heart ischemic disease, it decreases toxic liver damages, among them, in use of tuberculostatic agents and in correction of metabolic syndrome symptoms. EFFECT: enhanced effectiveness of elixir. 5 cl

Description

 The invention relates to medicine, namely to the pharmaceutical industry, to the creation of alcohol-containing complex preparations of natural origin based on plant materials, which have a tonic and adaptogenic effect.

 Herbal medicines are increasingly used in medical practice due to the identification of a number of positive aspects of their biological activity, comparative ease of preparation and low toxicity.

 There is a lot of information in the literature about the beneficial effect of herbal remedies on the functional state of a number of organs and systems of the human body, including the cardiovascular, central nervous system, gastrointestinal tract, liver, kidneys, etc. This is due to the fact that the complexes of biologically active substances contained in herbal preparations are structurally close to the metabolites of the body, biochemically compatible with it, and in the vast majority of cases they are not perceived as foreign. As a result, rationally selected plant complexes with a low level of toxicity and side effects can be safely used for appropriate periods of time at appropriate doses, which is especially important for normalizing mechanisms of long-term adaptation, disease prevention, and treatment of chronic diseases. And since in order to obtain stable normalizing changes in metabolism, it is necessary to bring to the conditions of homeostasis many enzymatic reactions and metabolic units of the body and maintain this state for a long time, multicomponent preparations of natural origin containing a harmoniously balanced composition of biologically active substances are better suited than any other to solve this problem. Alcohol-containing herbal preparations, called tinctures, are widely used among such agents. Tinctures of lemongrass, aralia, ginseng and others have long been used as fortifying agents. However, multicomponent mixtures, the so-called balms and elixirs, are preferred.

 Closest to the offer is Bittner's balm [Richard Bittner GmbH, Germany]. It contains 27 components from plant materials (white ash, racemic camphor, turmeric rhizome, degille root, myrrh, yellow gentian root, nutmeg fruit, stemless root root, bare licorice root, elecampane root rhizome, centaury grass, clove flowers, rhizome real galangal, ginger rhizome, curly thistle grass, clary yarrow grass, teriac, German rhizome rhizome, mullein flowers, peel of bitter orange fruit, calamus rhizome, bitter wormwood grass, dried juice of aloe vera leaves and trunks, cubeba fruits, star anise, peel of sweet orange fruit, leaves of a three-leaf watch), food coloring E 150-d, ethyl alcohol 96% and water.

 It is recommended as a general strengthening agent that improves liver and kidney function, normalizes cholesterol, and helps normalize the immune and endocrine systems.

 However, about half of the plant raw material contained in the balsam is exotic for our country, their current principles and possible side effects are unknown to Russian doctors, which limits the possibility of a broad recommendation of the balm to the weakened and sick people.

 The technical task of the present invention was to select the ratios of widely studied domestic plant components to create an elixir with improved pharmacological properties.

 To solve the technical problem, an elixir is proposed, which along with general strengthening and adaptogenic properties is additionally cardioprotective and hypolipidemic with antihypoxic and antioxidant activity.

For this purpose, we used the centuries-old experience of traditional medicine, as well as literary and our own data on the nature of the action of a large number of wild medicinal plants. The analysis of these data allowed us to propose an elixir containing water-alcohol extraction from 6 types of medicinal plants, taken in the following ratio, g:
Seeds of Siberian cedar pine - 90-95
Rhizomes with the roots of Eleutherococcus - 1.5-2.0
Hawthorn flowers - 0.7-0.9
Hawthorn fruits - 6.5-7.0
The fruits of the chokeberry chokeberry - 3.2-3.5
Birch buds - 2.3-2.7
Ethyl alcohol 95% - 550-600
Purified water - Up to 1000 ml
Moreover, this water-alcohol extraction is obtained by infusing plant materials in 50% ethyl alcohol in a ratio of raw materials: extractant of 1:10. The obtained extraction is characterized by the fact that the content of oxidizable substances in it in terms of tannin is 85 mg / l and the sum of flavonoids is 14 mg / l.

To obtain the target product to water-alcohol extraction add honey, sugar syrup, ethyl alcohol and water in the following ratio:
Water-alcohol extraction - 550-600 ml
Honey - 45-50 g
Sugar Syrup - 30-35 g
Ethyl alcohol 95% - 100-110 ml
Purified water - Up to 1000 ml
The content of oxidizable substances in the target product in terms of tannin is 50 mg / l, the sum of flavonoids is 7 mg / l.

 It is advisable to take the elixir for the prevention and treatment of atherosclerosis and coronary heart disease, to reduce toxic liver damage, including the use of tuberculostatics, as well as to correct the manifestations of the metabolic syndrome.

 Having been professionally engaged in the development of alcohol-containing products of natural origin of various directions of pharmacological action for many years, we selected medicinal plants for this elixir containing a rich complex of biologically active compounds aimed at increasing the protective functions of the body.

 So, the presence in the elixir of the extract from the fruits and flowers of hawthorn containing fatty oil, amino acids, including those affecting the cardiovascular system, flavonoids, trace elements (Cu, Mg, Cr, Zn) [Zavrazhnov V.I. et al. Medicinal plants: Therapeutic and prophylactic use, 4th edition. Voronezh: Publ. Voronezh State University, 1994, 480 p.] Provides a calming, hypotensive, cardiotonic, vasodilating and antispasmodic effect.

 Extract from birch buds, the main components of which are essential oils (bicyclic sesquiterpenoids, resin), grape sugar, vitamin C, saponins, phytocides [Dzhioev FK, “Medicinal plants that slow or weaken blastomogenesis”: Nonspecific drug prevention and treatment of cancer . - L .: Medicine, 1966, p. 81-90] gives the elixir a choleretic and diuretic effect.

 The presence of eleutherococcus with a high content in its root system of fatty and essential oils, pectin, resins, sugars, trace elements, eleutherosides A, B, C, D, E [Zavrazhnov V.I., (see above) and Sokolov S.Ya . et al. Handbook of medicinal plants (herbal medicine), 3rd edition, stereotyped. - M., 1990, 428 S.] promotes the positive effect of the elixir on the blood supply to the brain, the cardiovascular system, mental and physical performance, on the visual and auditory systems.

 The extract from the fruits of chokeberry aronia brings in sugar, organic acids, pectins, vitamins P and C, as well as trace elements (J, Mo, Mn) [Pharmacognosy: textbook, 3rd edition, revised and supplemented. - M., Medicine, 1991, 560 S.] and gives the elixir a hypotensive, capillary-strengthening and lipotropic effect.

 The extract from Siberian pine pine seeds, the main component of the elixir, enriches it with a number of biologically active substances, including unsaturated fatty acids, fat-soluble vitamins and a large number of trace elements (Mg, Fe, Mn, Cu, J, P) [P. Karetnikov . Materials of the scientific-practical conference of young hygienists and sanitary doctors. M., 1965, p. 189; He, Medicinal and raw materials of the Irkutsk region. - Irkutsk, 1968 - issue. 5, p. 46-48; He, Nutrition Issues, 1966 - vol. 5, p. 79-80], due to which it ensures the normalization of cholesterol metabolism, a decrease in the excitability of the nervous system and a hypotensive and antioxidant effect.

 Thus, in the inventive elixir there are components with potential tonic, antioxidant, lipid-lowering, anti-sclerotic, hypotensive and other effects.

 In experiments on animals of different species, we conducted an experimental study of the elixir for the presence of a specific pharmacological activity and its subsequent testing in a clinical setting.

STUDY OF HYPOLIPIDEMIC ACTIVITY OF ELIXIR
The experiments were performed on white outbred male rats weighing 220-240 g and guinea pigs males weighing 300-400 g. Male rats received a hypercholesterolemic diet for 31 days and some of them were additionally elixir in two doses - 1 and 2 ml orally through the probe. Under the influence of the elixir, a decrease in the liver of cholesterol (cholesterol) to 35% and triglycerides (TG) to 52% was observed. There was also a clear tendency towards a decrease in total cholesterol and triglycerides in serum and a significant increase in alpha-cholesterol to 33%. The comparison drug gemfibrozil reduced the content of cholesterol in the liver by 65%, without affecting the content of TG, and significantly increased the decreased alpha-cholesterol by 118%. A pronounced hypolipidemic effect of the elixir was also observed in male guinea pigs receiving cholesterol (0.5 g / kg in a mixture of fats) orally through a probe also for 31 days. A decrease in the content of total cholesterol in blood serum and liver by 35% and 16%, respectively, and TG by 17% and 49%.

STUDY OF ANTIOXIDANT EFFECT OF ELIXIR
In experiments on guinea pigs, the effect of elixir on the peroxidation of atherogenic apo-beta-containing lipoproteins was studied. In this case, the determination of fluorescent products of lipid peroxidation (LPO) was carried out. It is known that lipid peroxidation in atherogenic low-density lipoproteins significantly increase their damaging effect on the arterial wall and is currently recognized as one of the main factors of atherogenesis.

 The study showed that in animals fed a cholesterol-enriched diet, there was a significant increase in fluorescent products (LPO), both in blood serum and in atherogenic apo-beta-containing lipoproteins. With the additional introduction of the elixir, a clear decrease in fluorescence is noted, which indicates its pronounced antioxidant effect.

 Thus, in experiments conducted on animals with induced hyperlipidemia, the hypolipidemic effect of the elixir was revealed.

INFLUENCE OF ELIXIR ON THE ANTI-TOXIC LIVER FUNCTION
To detect violations of the antitoxic function of the liver, a hexenal test is widely used. The criterion for its assessment is the duration of the hexenal sleep of mice, expressed in minutes. Hexenal is known to break down mainly in the liver. Therefore, the duration of hexenal sleep depends on the functional state of the liver. The experiments were performed on 28 white outbred mice weighing 20-22 g. The elixir was tested in 2 doses - 0.15 ml and 0.30 ml per mouse when administered orally. The course of drug administration was 14 days. The hexenal test was performed on the 15th day of the experiment. The well-known hepatoprotector essentiale was chosen as the comparison drug. Hexenal was administered intraperitoneally at a dose of 80 mg / kg to both control and experimental animals. The longest sleep was observed in control mice - 49.29 min. Essential and elixir in 2 doses caused a significant reduction in hexenal sleep compared with the control, moreover, a more pronounced effect was observed at a dose of 0.15 ml per mouse. The duration of hexenal sleep decreased to 23.43 min, i.e. by 52.5%.

RESEARCH OF HEPATOPROTECTIVE ACTION OF ELIXIR
The experiments were performed on outbred male mice to which the elixir was administered orally at a dose of 0.15 ml per animal for 14 days. On the last day of the experiment, the studied, control mice, as well as those who received the hepatoprotective drug Essential, were injected intraperitoneally with carbon tetrachloride at a dose of 2.5 ml / kg of animal in the form of a 25% oil solution. After the introduction of carbon tetrachloride to mice, the death of animals was recorded after 24 hours and on the following days. The remaining mice were sacrificed and the mass of animals and the liver was determined, and the liver mass coefficient was calculated, and its histological preparations were studied.

 The study showed that in the groups of control animals a day after seeding, 100% death of mice was observed. In these animals, the highest coefficient of liver mass and the most significant morphological changes in it were recorded. In the group of mice receiving the essentials, only 4 out of 14 animals died, i.e. 71.4% survived. The studied elixir in a lower dose (0.15 ml) showed almost the same as the essential effect, the protective effect: out of 14 animals, 5 died, i.e. 64.3% survived. We can say that the hepatoprotective effect of essentialia and elixir is equally effective. Morphological changes in the liver were moderately expressed and rated at 2 points with a four-point system.

 Of particular note is the therapeutic efficacy of the elixir in the experimental tuberculosis process. The study was conducted on 120 outbred white male mice. For the experiment, we used the model of generalized tuberculosis (with predominant lung damage) caused by the introduction of a virulent culture of M. bovis bovinus 8 into the tail vein at a dose of 0.1 mg / mouse in the form of a bacterial suspension (0.2 ml). Treatment of mice with the main anti-TB drugs isoniazid and rifampicin began on the third day after infection and was carried out daily until the end of the experiment. Animals received the elixir at a dose of 0.15 mg / kg orally from the 10th day of infection. The course of elixir therapy was 14 days. The animals were removed from the experiment by decapitation on the 45th day after infection. The effectiveness of therapy was assessed by survival, by lung mass coefficients and by lung lesion index, which was assessed by a five-point system, and by seeding of mycobacterium tuberculosis from the spleen. The results of the study showed that by the 45th day after infection in the group of untreated mice, 45% of the animals died. In the groups receiving the main anti-TB drugs, death was not observed. The elixir, applied even as monotherapy, showed some therapeutic effect, the death of animals decreased to 10% (against 45% in the control). There was a tendency to change in other indicators - when the elixir was connected to etiotropic therapy, its effectiveness increased. So, in the treatment of rifampicin with the simultaneous administration of an elixir, such informative criteria as the index of lung damage and the seeding rate of mycobacteria were statistically significant. The mechanism of action of elixir in experimental tuberculosis may be due to the manifestation of hepatoprotective action, as well as, based on the composition of the elixir, its adaptogenic activity. In phthisiology, both immunotropic drugs and natural adaptogens are widely used as pathogenetic therapy agents, which are included in the complex treatment of tuberculosis and get positive results.

 From the foregoing, we can conclude that the inventive elixir has a pronounced anti-atherosclerotic, hepatoprotective, lipid-lowering effect and can be recommended for clinical trials to prevent atherosclerosis, with toxic liver lesions, including when using tuberculostats, when working under conditions of exposure to harmful chemical and physical factors during convalescence after infectious diseases that occurred with liver damage (hepatitis A, B and e ther), as well as a cardioprotective agent.

STUDY OF ACUTE AND SUB-SUBSTITUTE TOXICITY, IMMUNOTOXIC, ALLERGIZATIVE AND LOCALLY INFRASTRATING PROPERTIES OF ELIXIR
To study the acute toxicity of the elixir, 120 white rats (females and males), 60 white CBA mice (females and males), and 10 light-colored guinea pigs (females and males) were selected. The elixir was administered to animals once orally through a probe in various volumes and concentrations. The observation period for the animals was 14 days.

 With the introduction of the elixir at the rate of 30 mg / kg (maximum dose), no deaths were detected. During the experiment, no species and gender differences in sensitivity to the elixir were found in animals. The results of the experiments indicate that the elixir can be attributed to the class of relatively harmless substances.

 To study the subacute toxicity of the elixir, male Vistar rats with normal blood counts, the state of the cardiovascular, nervous and excretory systems were selected. Animals were divided into 4 groups: 1st — control, 2, 3, 4 — experimental. Experienced rats daily for 4 weeks were administered intragastrically an elixir in doses of 1500, 6000 and 30,000 mg / kg of body weight. The maximum of the administered doses was 20 times higher than the recommended dose for the clinical use of the elixir. During the experiment, rats noted a general condition (behavior, physical activity, body weight, appetite and coat condition). At the end of the experiment, we studied the morphological composition of the blood, some biochemical parameters, including total protein, cholesterol, transaminases and alkaline phosphatase levels, as well as the state of the cardiovascular and central nervous systems, excretory function of the kidneys. It was noted that the administration of an elixir at a dose of 1500 mg / kg to rats caused an increase in their motor activity. Rats that received it at a dose of 6000 mg / kg (group 3) experienced stronger excitement, in group 4 the animals were euphoric and immediately inhibited after the elixir administration, and became aggressive after 30 minutes. By the end of the month, in the 4th group (dose of an elixir of 30,000 mg / kg), the rats became lethargic and inhibited. In animals of the 2nd group receiving an elixir at a dose close to the therapeutic, a stimulating effect on the nervous system was clearly traced. In animals of all experimental groups, appetite increased. In rats receiving the maximum dose, a decrease in appetite was observed by the end of the 3rd week.

 In the study of peripheral blood, changes in key indicators fit into the framework of physiological norms. The results of studies of biochemical blood tests showed a decrease in total cholesterol in animals of the 2nd and 3rd groups. In the 4th group, cholesterol was higher than in the 2nd and 3rd groups, but lower than in the control.

 On the part of the cardiovascular system in experimental rats, no significant differences with control were revealed.

 In the study of kidneys, a decrease in diuresis was found in animals treated with an elixir at a dose of 30,000 mg / kg, while in the 2nd and 3rd groups, the excretory capacity of the kidneys was somewhat enhanced.

 At the end of the experiment, the animals were clogged with decapitation to determine the mass coefficients of the internal organs and histomorphological studies of them. A tendency toward an increase in the mass of organs in animals of the 2nd group was noted.

 Histomorphological examination of the internal organs was carried out in two experimental and control groups. The lungs, heart, liver, kidneys, spleen and adrenal glands were fixed in formalin, then dehydrated in aqueous solutions of ethyl alcohol and embedded in paraffin. Serial sections with a thickness of 7-8 μm were stained and subjected to microscopic examination.

 A histomorphological examination of the internal organs indicated the absence of their pathological changes.

 The allergenic properties of the elixir were studied in guinea pigs in vivo with single and triple parenteral sensitization and in a subacute two-week experiment in vitro on Wistar rats. In the experimental and control groups, animals of both sexes were used equally, 10 animals in each group. Sensitization of experimental animals was carried out according to the scheme: an elixir at a dose of 1500 mg / kg (group 1) and a dose of 7500 mg / kg (group 2) was administered for 3 days - the first injection subcutaneously, the next two intramuscularly thigh area. The resolving dose, equal to the sum of three sensitizing injections, the animals received intracardially on the 14th day after the first sensitizing injection. The control group of animals was injected subcutaneously and intramuscularly with a 40% solution of ethanol, and the animals were allowed to inject in the same way as the animals of the experimental groups. Over the next 30 minutes, animals were observed.

 During the entire period of observation of the clinical manifestations of anaphylactic shock - convulsions, feces and urine separation, the lateral position of the animal, sneezing, frequent scratching, and a drop in body temperature - there were practically no signs. The body temperature of animals in both experimental groups did not significantly differ from control animals. Ruffling of wool was noted in one animal of the first group and in two animals of the second group. In the control group, two animals also showed similar effects after intracardiac injection. Those. such an animal reaction can be considered as adaptive. Therefore, the elixir does not cause allergic reactions in an immediate manner.

 The study of the "delayed" type hypersensitivity reaction was carried out on albino guinea pigs. The animals of the experimental groups were immunized once in the pads of 4 legs. The elixir was administered at a dose of 1500 mg / kg (group 1) and at a dose of 1500 mg / kg (group 2) in a mixture with incomplete Freund's adjuvant (NAF) in a ratio of 1: 1. In the control group of animals, only NAF was introduced into the paw pads. On the 21st day, an elixir was injected intracutaneously at a dose of 16 mg / kg into the lateral surface of the experimental animals. Assessment of the skin reaction was carried out after 1, 24 and 48 hours. There was no positive reaction to the intradermal administration of the elixir in the resolving dose.

 Thus, the experiments showed that the elixir does not cause the development of hypersensitivity in immediate and delayed types.

 With intragastric administration of elixir for two weeks at a therapeutic dose on the 14th day of the experiment, a decrease in the absolute number of eosinophils in the peripheral blood was noted, which should be considered as a manifestation of the hyposensitizing properties of the drug.

 On 30 white outbred rats, the locally irritating properties of the elixir were studied. Rats of the 1st, 2nd and 3rd groups were injected subcutaneously daily for 3 days with 0.5 ml of 10%, 20% and 30% aqueous solution of elixir, respectively. At the injection site, a visible inflammatory reaction was not observed in any group of animals.

 In the following series of experiments, 6 rabbits were subconjunctively administered with a 20% elixir solution. The animals were observed for 10 days. Local action is not marked. This suggests that the elixir does not have locally irritating properties.

From the foregoing it follows that
- according to the parameters of acute toxicity during intragastric administration to mice and rats, the elixir can be assigned to the class of relatively harmless substances;
- during the subacute experiment revealed a moderate stimulating effect on the central nervous system. The elixir did not cause any disturbances in the functional activity of the internal organs and systems of the animal organism;
- according to the results of a subacute experiment, the elixir has a hypocholesterolemic effect;
- the elixir does not have immunotoxic and allergenic properties;
- the elixir does not exert a locally irritating effect upon subcutaneous and subconjunctival administration to experimental animals.

CLINICAL TESTING OF ELIXIR
Clinical studies of the inventive elixir are aimed mainly at studying its effect on patients with coronary heart disease (CHD).

 Often, IHD occurs in combination with arterial hypertension (AH), obesity (Og), impaired lipid metabolism, impaired glucose tolerance or non-insulin-dependent diabetes mellitus. It is believed that these diseases are based on common metabolic disorders and therefore this combination is called "metabolic syndrome X". The use of drugs that improve metabolic processes, in this regard, is pathogenetically justified. Since in the animal experiment the inventive elixir significantly reduces the cholesterol (cholesterol) content in the blood serum, exhibits a lipid-lowering and antioxidant effect, it was decided to conduct a clinical study of it in patients with metabolic syndrome.

 The study included 34 patients with identified metabolic syndrome. All patients received a lipid-lowering diet for 10 days. Patients received beta-blockers (metoprolol), nitro drugs (nitroglycerin, nitrosorbide), antiplatelet agents (aspirin), and diuretics (hypothiazide) in 50% of cases. A control group of patients in the amount of 15 people received only basic therapy, in the main group (19 people), patients additionally took an elixir of 15 ml 3 times a day. The average age in the groups was 54 and 51 years, the duration of hypertension in patients ranged from 7 to 11 years, hypodynamia was present in both groups, and abdominal obesity was higher in the main group. The duration of smoking, the need for its quantity, and alcohol consumption by groups did not differ significantly. A burdened heredity of hypertension, coronary heart disease, OG, and diabetes mellitus was present in both groups.

 To assess the effectiveness of therapy, generally accepted methods of clinical examination were used: assessment of the general condition, clinical examination, dynamics of blood biochemical parameters, blood lipid spectrum, daily monitoring of an electrocardiogram, glucose tolerance test with determination of insulin level, echocardiography, bicycle ergometry.

 At the initial examination, all patients complained of fatigue, shortness of breath, heaviness, pain in the heart and behind the sternum. A month after the start of the use of the elixir, a decrease in the severity of subjective symptoms was noted compared with the control group, which is even more noticeable after 2 months of taking the drug. To the greatest extent, chest pains, irritability, sleep disturbance decreased. In both groups, there was a slight decrease in both systolic (SBP) and diastolic (DBP) blood pressure. 2 months after treatment, both SBP and DBP decreased, both maximum and working, and after 2 months there was a more significant and steady decrease in pressure than after 1 month. Against the background of basic therapy, there was an increase in total cholesterol, triglycerides (TG), very low density lipoprotein cholesterol (VLDL cholesterol), an increase in atherogenic coefficient (CA), with a slight decrease in high density lipoprotein cholesterol (HDL cholesterol). When taking the elixir, total cholesterol, LDL cholesterol, and CA decreased, but TG and VLDL cholesterol increased slightly. At the same time, there was an increase in HDL cholesterol, usually reduced in patients with coronary artery disease.

 On an empty stomach, the glucose and insulin levels in the blood did not differ from the norm. A glucose tolerance test (TSH) led to a significant increase in insulin levels. Against the background of basic therapy, there was a tendency to an increase in basic and glucose-stimulated insulin in the blood. In the main group receiving additional elixir, glucose and insulin levels were lower after TSH. The decrease in blood glucose from 9.8 + 0.6 to 8.4 + 0.4 mmol / L and increased basal insulin from 137.4 + 2.3 to 87.5 + 12.7 was significant. This indicates a favorable effect of the elixir in relation to the main pathogenetic link of the metabolic syndrome - insulin resistance. With daily monitoring of the ECG, a decrease in the number of pain ischemia on average per day, the duration of pain and painless ischemia, especially in the daytime when taking the elixir, was revealed.

 According to bicycle ergometry, when taking the elixir, compared with the control group, there was a moderate increase in the total amount of work, load time, an improvement in the coefficient of expenditure of the chronoinotropic reserve, and a decrease in the recovery period.

 In the echocardiography indices for the control group, no significant dynamics were detected. In the group receiving the elixir, after 2 months, a moderate improvement in systolic function of the heart was noted (an increase in the ejection fraction, the shortening fraction). In this case, there was a decrease in hypertrophy and myocardial mass, an improvement in the diastolic function of the heart — an improvement in the ratio of the rate of early (E) and late (A) diastolic filling of the left ventricle, a decrease in the time of slowing blood flow (DT) and the time of isovolumetric relaxation (IVRT).

 Thus, the results obtained in the study indicate that the introduction of an elixir in the basic therapy of patients with coronary heart disease with metabolic disorders has a pronounced improvement in the dynamics of the course of coronary heart disease. In addition, the course use of the elixir leads to the normalization of impaired lipid metabolism, a decrease in LDL cholesterol, an increase in the decreased content of HDL cholesterol, as well as a decrease in the increased level of insulin in the blood.

 In another clinical study, the inventive elixir was used in 15 patients with atherosclerosis with severe hypercholesterolemia and 15 patients with chronic hepatitis with symptoms of fatty hepatosis. The control group (10 patients) received Essential Forte.

 At the initial examination of patients of the first group, fatigue, shortness of breath, heaviness and stitching and compressive pains in the heart region, sleep disturbance, irritability were observed. Headaches, dizziness, noise in the head and ears, memory impairment, mood instability, lethargy were noted. Patients of the second group noted complaints of general weakness, pain and heaviness in the right hypochondrium, belching, nausea, vomiting, flatulence, impaired stool. Two weeks after the start of taking the elixir (1-2 teaspoons 3 times a day before meals), the subjective signs of the disease in both groups became significantly less pronounced and did not have a statistically significant difference in comparison with the control group (in patients taking essentials) .

 From objective indicators, the results of an ultrasound examination of the liver, biliary tract, gall bladder and pancreas, clinical blood and urine tests, the dynamics of the main biochemical blood parameters reflecting protein, lipid and carbohydrate metabolism were evaluated. ECG indicators and psychophysical state based on the SAN test (well-being, activity, mood).

 In the 1st group of patients with the phenomena of atherosclerosis concomitant diseases were: arterial hypertension (7 people), peptic ulcer (2 people) and diabetes mellitus (2 people). In the second group, patients with liver damage had: chronic hepatitis (7 people), chronic hepatocholecystitis (2 people), fatty hepatosis (6 people) and associated diseases: arterial hypertension (4), osteochondrosis (3), chronic colitis (3).

 By the end of treatment, the subjective symptoms of the disease significantly decreased. The psychophysical state of patients improved, mood improved, insomnia decreased. In the group of patients with atherosclerosis, there were signs of an improvement in heart function according to ECG and the clinical picture of the disease. In patients with liver damage, a positive dynamics of the state of the liver and gall bladder was observed according to ultrasound. In patients with liver diseases, there is a tendency to restore hemoglobin levels. In both groups of observations, a positive effect of the course application of the elixir on biochemical parameters was established. The phenomena of dysproteinemia decreased, hypercholesterolemia and the level of beta-lipoproteins decreased. The signs of cytolytic, mesenchymal and cholestatic syndrome in patients with chronic hepatitis and fatty hepatosis decreased. The positive dynamics of the indicators during the observation did not differ from the trend established in patients receiving treatment with essential forte.

 Thus, the conducted experimental and clinical studies of the inventive elixir convincingly showed that the drug has a restorative effect, and also normalizes impaired liver function and lipid metabolism. Under its influence, the increased level of atherogenic lipoproteins and their oxidation decreases, and the reduced content of antiatherogenic lipoproteins increases. In the complex therapy of patients with coronary heart disease with metabolic disorders, the drug clearly improves the dynamics of the course of the disease, improves glucose tolerance, increases physical performance, and reduces hyperlipidemia.

 In connection with the foregoing, the claimed elixir can be recommended for the prevention and treatment of astheno-vegetative syndrome, as a general strengthening agent, as well as for the prevention and treatment of patients with coronary heart disease with hyperlipidemia (types IIb-IV hyperlipidemia), to reduce toxic liver damage and to correct the manifestations of the metabolic syndrome.

 We give the scheme for obtaining the proposed elixir.

 91 g of Siberian cedar pine seeds, 1.69 g of rhizomes and roots of Eleutherococcus, 0.84 g of hawthorn flowers, 6.76 g of hawthorn fruit, 3.38 g of chokeberry fruit (chokeberry) and 2.53 g of birch buds are crushed to a particle size of not more than 7 mm and filled with 1000 ml 50% ethyl alcohol, i.e., in the ratio of raw materials: extractant 1:10, and insist for 15 days at room temperature with stirring, after which the water-alcohol extraction is separated from the raw material.

 The content of oxidizable substances in water-alcohol extraction in terms of tannin is 85 mg / l and the sum of flavonoids is 14 mg / l.

 To 592.5 ml of the obtained aqueous-alcoholic extract, add 50 g of natural honey, 34.4 g of sugar syrup, 108.3 ml of 95% ethyl alcohol and make up to 1000 ml with water. The solution is stirred, standing for at least 3 days and decanted.

 The elixir is a transparent brown liquid, burning taste, with a specific aromatic odor.

 The content of oxidized substances in the elixir in terms of tannin is 50 mg / l, the sum of flavonoids is 7 mg / l.

Claims (4)

1. An elixir with a restorative and adaptogenic effect, including water-alcohol extraction of medicinal plants, characterized in that it contains water-alcohol extraction of Siberian cedar pine seeds, rhizomes and roots of Eleutherococcus, hawthorn flowers and fruits, chokeberry fruits and birch buds, obtained by insisting them in 50% ethanol in the ratio of raw materials: extractant 1:10, with the content of oxidized substances in the extraction in terms of tannin 85 mg / l and the sum of flavonoids 14 mg / l, additionally contains U, sugar syrup, 95% ethyl alcohol and water in the following ratio, g:
Water-alcohol extraction - 550 - 600 ml
Natural honey - 45 - 50
Sugar Syrup - 30 - 35
Ethyl alcohol 95% - 100 - 110 ml
Purified water - Up to 1000 ml
and is characterized by the content of oxidizable substances in terms of tannin, equal to 50 mg / l, and the sum of flavonoids 7 mg / l. 2. The elixir according to claim 1, characterized in that the aqueous-alcoholic extract contains medicinal plants in the following ratio, g:
Seeds of Siberian cedar pine - 90 - 95
Rhizomes with the roots of Eleutherococcus - 1.5 - 2.0
Hawthorn flowers - 0.7 - 0.9
Hawthorn fruits - 6.5 - 7.0
The fruits of the chokeberry chokeberry - 3.2 - 3.5
Birch buds - 2.3 - 2.7
Ethyl alcohol 95% - 550 - 600 ml
Purified water - Up to 1000 ml
3. The elixir according to claim 1, characterized in that it is intended for the prevention and treatment of atherosclerosis and coronary heart disease.  4. The elixir according to claim 1, characterized in that it is intended to reduce toxic liver damage, including when using tuberculostatics.  5. The elixir according to claim 1, characterized in that it is intended to correct the manifestations of the metabolic syndrome.