Method of exerting an adaptive restorative effect on the human body

Abstract

The present invention relates to the field of medicine, and more particularly to restorative medicine. It can be used to enhance a person's adaptive capabilities through exposure of the body to a hypoxic effect. The method is carried out during the first half of the day. It is essential that oxygen saturation and heart rate are measured continuously up to and during exposure to the effect. A hypoxic gas mixture having an oxygen concentration of up to 16% is fed to the patient, wherein a feed rate of 45-52 l / min is maintained for an exposure time of 3 minutes. Hydrogen for inhalation is then fed continuously via a nasal cannula while the feed rate of the hypoxic mixture is reduced to 20 l / min for a period of from 5 to 10 min. When saturation decreases to 80%, the oxygen concentration is automatically increased to 21% until the patient's oxygen saturation and heart rate reach their initial values. The duration of a single procedure, including alternating breathing of the gas mixture and the mixture with hydrogen, is 40-60 minutes, wherein a single procedure consists of 4-5 cycles. Between 10 and 21 procedures are performed at one day intervals. The method enhances the adaptive restorative capability of the body without inducing side effects.

Description

[0001] A METHOD OF ADAPTATION AND RESTORATIVE EFFECT ON THE HUMAN BODY

[0002] AREA OF TECHNOLOGY

[0003] The invention relates to physiology, restorative and preventive medicine and can be used to most effectively increase non-specific adaptive capabilities of a person, train and restore physiological mechanisms of oxygen utilization, and increase resistance to extreme and sub-extreme environmental factors.

[0004] PRIOR ART

[0005] In recent years, the method of training the body's adaptive resources by breathing through a mask with hypoxic gas mixtures containing 10-14% oxygen has become very popular.

[0006] With this method of creating and delivering gas mixtures, based on the principle of membrane gas separation of ordinary atmospheric air and implemented by a number of companies (Bionova, Hypoxia Medical Academy, etc.), the adaptive effect of hypoxia is more pronounced due to the use of intermittent (interval) schemes of hypoxic stimulation of the body (5-7 minutes of breathing a hypoxic gas mixture, then a pause - breathing ordinary atmospheric air for 3-5 minutes). At the same time, using this version of hypoxic training, it is possible to avoid a number of negative effects of low barometric pressure (barotopathies, excessive gas formation in the intestines, barodentalgia, etc.). The prior art includes a "Method for increasing non-specific adaptive capabilities of a person based on hypoxic-hyperoxic gas mixtures" under patent RU 2289432 published on 20.12. 2006.

[0007] The method involves a course of hypoxic-hyperoxic training, each consisting of six hypoxic-hyperoxic cycles. Each cycle consists of alternating 5-minute normobaric hypoxic exposures with 3-5-minute hyperoxic exposures. The first five hypoxic exposures are administered with a mixture containing 11% oxygen, while the subsequent five hypoxic exposures are administered with an air mixture containing 10% oxygen. Hyperoxic exposures are administered with a mixture containing 30% oxygen. If necessary, five more hypoxic-hyperoxic cycles can be performed, each alternating 5-minute normobaric hypoxic exposures with a mixture containing 10% oxygen and 5-minute hyperoxic exposures with a mixture containing 30% oxygen. The treatments are administered every other day.This method improves the safety and effectiveness of short-term hypoxic-hyperoxic normobaric training by exhibiting a pronounced membrane-stabilizing effect, which contributes to increased resistance of liver and brain cells to the effects of reactive oxygen species. Preliminary studies on male volunteers also demonstrated that hypoxic-hyperoxic training produces the expected training effects (increased hypoxia resistance based on subjective self-reports and objective criteria—SaO2 and heart rate dynamics, Stange test values, optimization of autonomic regulation of blood circulation at rest and autonomic reactivity to test loads, improved respiratory function, etc.) over shorter time intervals (8-10 sessions), and these effects are more pronounced compared to a standard hypoxic-hyperoxic interval training regimen.

[0008] Currently, molecular hydrogen can be used as a new therapeutic agent with antioxidant, anti-inflammatory and anti-apoptotic properties (1).

[0009] Molecular hydrogen as a medical device has attracted increasing scientific attention since its antioxidant effect was identified.

[0010] Inflammatory cytokines, vascular adhesion factors, apoptotic signals, and cellular senescence signals—the consequences of exposure to reactive oxygen—lead to inflammation, atherosclerosis, aging, and oncogenesis. Exposure to reactive oxygen, stress, toxins, nutrients, and irritants also lead to the oxidation of deoxyribonucleic acid, protein oxidation, lipid oxidation, and sugar oxidation. The beneficial effects of molecular hydrogen in clinical settings are particularly noticeable in diseases triggered by stressful situations. Molecular hydrogen influences cellular signaling and acts as an alkalizing agent.

[0011] These identified mechanisms of action have potential for application in clinical medicine. Hydrogen therapy based on 0.9% NaCl may prove to be a specific and effective innovative treatment for oxidative stress.

[0012] It is known that molecular hydrogen exhibits a strong chemical affinity for free oxidizing radicals such as the hydroxyl radical and is able to selectively neutralize this most cytotoxic radical (1).

[0013] By selectively neutralizing hydroxyl radicals, molecular hydrogen is able to preserve the activity of less reactive oxygen radicals, which are involved in many processes of normal physiological regulation of cellular, tissue, and organ activity. Through its antioxidant power, molecular hydrogen can also exhibit anti-inflammatory, anti-apoptotic, and anti-allergic properties. (2)

[0014] It is known that molecular hydrogen exhibits a strong chemical affinity for free oxidizing radicals such as the hydroxyl radical and is capable of selectively neutralizing this most cytotoxic radical.

[0015] Molecular hydrogen is capable of selecting between harmful and beneficial reactive oxygen species. By exerting its antioxidant power, molecular hydrogen can also demonstrate anti-inflammatory, anti-apoptotic, and anti-allergic properties.

[0016] Known from the prior art is patent No. 2668883 “Method of hydrogen therapy” based on 0.9% NaCl for improving the health of the human body, published on October 4, 2018

[0017] The uniqueness of the hydrogen therapy method using 0.9% NaCl lies in the direct introduction of molecular hydrogen into the blood of study participants via intravenous drips. This increases the effectiveness of molecular hydrogen, which impacts the speed of treatment and the effectiveness of health improvement.

[0018] The hydrogen therapy method based on 0.9% NaCl is based on the goal of increasing the effectiveness and efficiency of treatment for various diseases. This goal is achieved by administering a 50 / 50 solution of 99.99% molecular hydrogen grade A and 0.9% NaCl directly into the blood of study participants via intravenous drip.

[0019] The cause-and-effect relationship between the combined effects of hydrogen therapy using 0.9% NaCl and the medical outcome is as follows: molecular hydrogen is delivered intravenously via a drip into the human bloodstream along with a 0.9% NaCl solution. This solution, known medically as a saline solution, has an osmolarity similar to that of blood, meaning it does not cause blood cell destruction and is widely used for intravenous drug administration.

[0020] The “Method for treating hypercapnic respiratory failure with signs of secondary pulmonary arterial hypertension” is known under patent RU 2806575, published on November 1, 2023.

[0021] Known treatments for respiratory failure include oxygen therapy, respiratory support methods (non-invasive ventilation (NIV) and artificial ventilation (AV)), standard drug therapy (participants in studies according to the severity of COPD exacerbation according to the recommendations of the Global Initiative for Chronic Obstructive Lung Disease (GOLD), physiotherapy and adjuvant drug therapy with drugs containing magnesium, B vitamins and LKapHHTHH.

[0022] However, prolonged use of oxygen leads to hyperoxidative damage to the lungs, causing necrosis of the airway epithelium, pulmonary capillary endothelium, and the transformation of type II alveocytes into type I alveocytes. Oxidative stress results in impaired mucociliary clearance, the development of atelectasis, and pulmonary hypertension. Non-invasive ventilation is not always effective. In patients with severe respiratory failure, signs of hypoxemia and hypercapnia, non-invasive respiratory support fails to achieve the desired results in 30% of cases.Noninvasive ventilation is also associated with such disadvantages as the need for active collaboration between study participants and medical personnel; the inability to apply high inspiratory and expiratory pressures; a high rate of aerophagia; a high rate of aspiration of oral and gastric contents; maceration, including skin necrosis, at the sites of mask contact; hypoxemia when the mask is displaced; and nosebleeds.

[0023] The method described in patent RU 2806575 involves inhalation of nitric oxide and water vapor aerosol with reactive hydrogen, with the hydrogen concentration in the mixture ranging from 0.1 to 0.3% by volume. Nitric oxide inhalation is administered at a dose of 100 ppm and is combined with water vapor aerosol inhalation during noninvasive ventilation (NIV) in BiPAP ST mode. The inhalation gases, nitric oxide, and aerosolized water vapor are delivered through an adapter directly into the NIV circuit. Inhalation therapy combining NIV in BiPAP ST mode, nitric oxide at a dose of 100 ppm, and water vapor aerosol is administered for 90 minutes twice daily for 10-14 days, in the morning and evening.

[0024] The method increases the effectiveness of respiratory failure treatment by using positive airway pressure, altering ventilation mechanics, "unloading" the respiratory muscles, increasing alveolar ventilation, regulating vascular tone and correcting signs of vascular endothelial dysfunction, as well as effectively combating ischemia of internal organs and tissues of the human body by improving oxygen transport and utilization, correcting metabolic disorders, achieving positive dynamics in the form of a reduction in the manifestations of respiratory failure and increasing tolerance to physical activity.

[0025] Patent RU 2784998 “Method for treating respiratory failure (hypoxemia) in patients who have had a sars-cov-2 virus infection” is known.

[0026] The COVID-19 treatment protocol includes inhalation of a thermal mixture of helium and oxygen, consisting of a helium concentration of 50 to 79% by volume and oxygen of 21 to 50% by volume, at a temperature of 55 to 75°C for up to 30 minutes per day. Additionally, nitric oxide at a dose of 75-80 ppm is inhaled through a nasal cannula for 90 minutes per day, followed by inhalation of an aerosol mixture of water vapor with reactive hydrogen, with the concentration of the latter in the mixture ranging from 0.1% to 0.3% by volume, for 90 minutes per day. All inhalations are carried out for at least 10-14 days. The use of the invention allows for the effective treatment of ischemia of internal organs and tissues of the human body due to the fact that inhalation of a thermal mixture of helium and oxygen improves oxygen transport to tissues, an aerosol with atomic hydrogen reduces the manifestations of hypoxemia, increases tolerance to physical activity, and reduces endothelial dysfunction.

[0027] The closest in technical essence is the METHOD FOR TREATMENT OF RESPIRATORY FAILURE according to patent RU 2784998, which has the following common features:

[0028] - hypoxic effect on the human body of a gas mixture with a certain oxygen content. - inhalation through a nasal cannula of an aerosol mixture of water vapor with molecular hydrogen.

[0029] The technical problem, which is addressed by the development of a method for preventive and modulating effects on humans, is the reduction of the level of reactive oxygen species in the body, which increase the formation of oxidative stress factors and inflammation markers, while simultaneously increasing the proportion of antioxidant markers.

[0030] The invention aims to reduce the amount of highly active free radicals (hydroxyl radical, peroxynitrite) in the human body, an excess of which causes oxidative stress, which damages all cellular components. Oxidative stress underlies premature aging and the development of most non-communicable diseases.

[0031] DISCLOSURE OF THE INVENTION

[0032] The amount of free radicals is associated with the deterioration of brain processes (neuroprotective effect, stimulation of the growth of nerve cells and new synapses, as well as an increase in markers of synaptic plasticity (for example, hippocampal neurogenesis) when using GS (gas mixtures), in a short-term mode in the wide practice of restorative and preventive medicine.

[0033] The developed method of adaptive and restorative impact on the human body is implemented by exposing the study participants to the supply of a gas mixture (GM) with an oxygen concentration of up to 16 vol.%, and a supply rate of the said gas mixture of 45-52 l / min.

[0034] Simultaneously with the introduction of oxygen to the air-gas mixture, inhalation hydrogen is introduced at a rate of 1-2 l / min. Hydrogen is continuously introduced, and the oxygen concentration in the gas mixture is reduced to 6-8 vol.%, while the oxygen flow rate is gradually reduced to 20 l / min. This results in a hydrogen concentration of 3-4 vol.% of the total volume of the gas mixture. Saturation is continuously measured during exposure to the gas mixture, and when it decreases to 80%, oxygen is automatically introduced to a concentration of 21%, ensuring that saturation and cardiac output return to pre-hypoxia levels.

[0035] The procedures are carried out using devices in the form of special inhalers or “inhalation systems”, in which the exposure of the study participants to GS is carried out by breathing through a respirator mask and in combination with the supply of inhalation hydrogen using a cannula,

[0036] - a person is exposed to a hypoxic, normobaric artificial gas mixture with a parallel supply of hydrogen; the method involves the deep, simultaneous exposure of the stated gas mixture to the body through the respiratory system, ensuring an effective effect at the molecular-cellular level.

[0037] Table 1 shows the parameters of the gas mixture supply mode when exposed to the human body. Table 1

[0038] To assess the body's biological response to hypoxic training, the body's antioxidant system was chosen. Therefore, the first and most important step is to assess the body's oxidative stress (OS) status. This requires measuring the levels of free radicals (FR) and antioxidant capacity (AOC).

[0039] To assess the OS, a portable analyzer FORM Plus was used, which allows for quantitative rapid determinations in whole blood samples (free radical content (FORT test), total antioxidant capacity (FORD test), uric acid level, hemoglobin, hematocrit).

[0040] To assess the study participants' OS status, FORT (free radical assay) and FORD (antioxidant capacity assay) were performed. Analysis of FORT and FORD results allowed us to assess the participants' condition and determine the optimal course of action.

[0041] ROS formation is a fundamental in vivo phenomenon that is precisely regulated and underlies normal cellular metabolism. Research into the pathological effects of reactive oxygen species (ROS) began in the second half of the 20th century. The fact that ROS are formed not only in cells with reduced oxygen levels but also in all aerobic cells precluded a direct link between excess ROS and the development of pathological processes. Oxidative stress (OS), the toxic effects of free radicals excessively produced by mitochondria, is believed to play a significant role in the pathogenesis of postoperative complications and multiple organ dysfunction / failure. [1]

[0042] In most diseases, oxidative stress is a consequence of the underlying pathology; the uncontrolled proliferation of toxic radicals causes more cellular damage than the underlying disease. This stress is involved in the development of generalized changes in capillary permeability and tissue diffusion, characteristic of multiple organ failure.

[0043] Under normal physiological conditions, small amounts of oxygen consumed by mitochondria are constantly converted into superoxide anions, hydrogen peroxide, and hydroxyl radicals. Excessive production of these radicals is a damaging factor, and the cell has a natural antioxidant system for this purpose. It is represented by enzymes, among which the most important are Mn2+- and Cu2+-dependent superoxide dismutases (SOD), glutathione peroxidase (GPO), glutathione reductase (GR), and catalase (CAT). SOD converts superoxide anions into hydrogen peroxide, which is then transformed into water by other enzymes: glutathione peroxidase (GPO), catalase (CAT). [2]

[0044] Oxidative stress in the human body develops systemically in several stages, ultimately increasing the concentration of free radicals (reactive oxygen species, H2O2, etc.) and triggering inflammation and autophagy. Scientists are primarily focused on studying the consequences that develop in patients as oxidative stress products accumulate.

[0045] The dominant view in the literature is that damage to biomembranes plays a key role in the development of oxidative stress. The subsequent course of the reaction can follow two pathways: the first is associated with the activation of free radical formation, which can both inhibit enzyme activity and activate lipid peroxidation; the second pathway is associated with a decrease in the activity of the antioxidant system, which also leads to the activation of lipid peroxidation. Although free radical processes are typical in various pathological conditions, their mechanisms of development may have unique characteristics.

[0046] Thus, in type 2 diabetes mellitus, severe vascular damage occurs due to the accumulation of free radical oxidation products. Vascular complications can significantly worsen the course of diabetes mellitus, involving all organs and systems in the pathological process. In diabetes mellitus, increased levels of reactive oxygen species (ROS) can contribute to damage to the vascular endothelium and the subsequent development of endothelial dysfunction. The balance between endothelium-dependent relaxing factors and endothelium-dependent constricting factors is crucial for the control of local vascular tone and function under normal conditions.

[0047] Experimental data have shown that ROS play a significant role in the pathophysiology of hypertension. The vasculature is a rich source of NADPH oxidase, which produces the majority of reactive oxygen species and plays a significant role in kidney dysfunction and vascular damage.

[0048] Recent studies have shown that oxidative stress is an important factor in endothelial damage in hypertension, being associated with increased production of prooxidants such as superoxide anion, hydrogen peroxide, decreased nitric oxide synthesis and reduced bioavailability of antioxidants.

[0049] Oxidative stress has been shown to be associated with endothelial dysfunction, inflammation, hypertrophy, apoptosis, cell migration, fibrosis, and angiogenesis in association with vascular remodeling in hypertension.

[0050] The development of oxidative stress during acute inflammatory reactions is characterized by rapid accumulation and excessive increases in metabolite concentrations, when the body is unable to mobilize its own antioxidant reserves. In some cases, certain metabolites are released that alter the state of TGF-β family proteins and increase activin protein concentrations, which in turn contributes to the development of inflammatory reactions, further exacerbation of oxidative stress, and hyperactivation of the immune system.

[0051] In the early stages of the inflammatory process, the concentration of proinflammatory cytokines, such as interleukins IL-6 and IL-1β (immune response factors), increases in the body. Subsequently, another group of cytokines (IL-2, IFN-y (type II interferons)) is activated. [3]

[0052] Oxidative stress can cause eye diseases (cataracts, retinal detachment), kidney failure, skin diseases (dermatitis, psoriasis), heart disease (heart attack), joint diseases, lung diseases (bronchial asthma), brain diseases (stroke, Parkinson's disease), vascular diseases (atherosclerosis, hypertension), stomach and intestinal diseases.

[0053] Interval hypoxic training (IHT) provides the ability to purposefully dose the stimulus strength and the amplitude of hypoxic mixture fluctuations. The goal of IHT is to induce the development of general nonspecific reactions that correspond to the symptom complex of the integrated nonspecific adaptive response of activation or training, described and studied by Rostov scientists Garkavi L.Kh., Ukolova M.A., Kvakina E.B., Kuzmenko T.S. and Shikhlyarova A.I. [4,5]. Hydrogen levels in the blood and tissues reach saturation within 2 or 3 minutes after the start of inhalation of hydrogen gas. The level of hydrogen gas in the blood reaches 3.0-4.0% in GS after inhalation. Arterial blood oxygen saturation is not affected, because hydrogen gas does not bind to hemoglobin, and blood pressure and pulse rate also do not change under steady state conditions. After inhalation stops, the level of hydrogen gas in the blood decreases rapidly as it is eliminated from the lungs.

[0054] The method is carried out as follows.

[0055] Study participants lie supine on a special couch. The equipment used for the hypoxic therapy procedure, combined with inhalation hydrogen delivery, consists of specialized inhalers or "inhalation systems." Participants are exposed to the gas mixture through a respirator mask (in combination with the delivery of inhalation hydrogen via a cannula). The equipment has the following capabilities: 1. Maintaining the concentration of inhalation hydrogen in the inhaled air within 0.3-4 vol.%. 2. Automated training using biofeedback (pulse and saturation monitoring). These parameters can be set and subsequently monitored beforehand, as well as during training, with the ability to vary the intensity.Hypoxic gas mixtures with the simultaneous use of hydrogen therapy are delivered to the study participant through a mask and are created by the OXYTERRA device, Oxyterra LLC, equipped with a gas analyzer (Oxybabymed WITT (Germany)), a pulse oximeter to record SaO2 sanitation and the dynamics of changes in heart rate.

[0056] Before training, the subject undergoes a hypoxic test to determine their individual sensitivity to hypoxia. This test involves a 15-minute hypoxic test (administering an 11% O2 mixture through a mask) and measures the individual reduction in SaO2 saturation and heart rate increase. Based on these data, the device automatically calculates the recommended oxygen concentration for the subsequent hypoxic training session.

[0057] The training procedures begin with the administration of a hypoxic mixture containing 11-16% vol. oxygen at a gas mixture flow rate of 45-52 l / min, with an exposure time of 3 minutes. Hydrogen is then administered through a nasal cannula at a rate of 1-2 l / min. The oxygen level in the hypoxic mixture is automatically reduced to 6-8% vol. (O2) until the SaO2 saturation reaches an individual minimum or the heart rate reaches an individual maximum (whichever occurs first). Hydrogen is continuously administered to the subject through the cannula throughout the training session, while the oxygen concentration in the gas mixture begins to decrease to 6-8% vol. and the flow rate is gradually reduced to 20 l / min. The hydrogen concentration reaches 0.3% of the total gas mixture volume. The oxygen content in the gas mixture is then increased to 21% (O2) until SaO2 and heart rate reach their initial (pre-hypoxia) values.The duration of individually dosed hypoxic exposure varies from 5 to 10 minutes, this is ensured by the “Biofeedback” function - automated training using the biological feedback method (pulse and saturation control), which is implemented by continuously measuring saturation when exposed to a gas mixture and when it decreases to 80 vol.%, normoxia of 21% (02) is automatically applied.

[0058] A single treatment lasts 40-60 minutes. Four to five cycles of treatment are performed during the treatment. A total of 10-15 treatments every other day are recommended, and the training can be extended to 18-21 treatments.

[0059] EMBODIMENTS OF THE INVENTION.

[0060] This method was tested as part of a medical rehabilitation program for people who have recovered from COVID-19.

[0061] The study involved 25 participants, including 15 women and 10 men. All subjects experienced difficulties with self-care and noted increasing weakness with minimal physical activity, including standing. Participants were trained in person in a hospital setting. The rehabilitation course of interval normobaric hypoxic therapy with hydrogen therapy consisted of 21 sessions, lasting a total of 21 days, every other day. Progression to more challenging exercise levels during the sessions was only performed if SpO2, heart rate, respiratory rate (RR), and laboratory parameters of oxidative stress (FORD) stabilized. During training, saturation was not allowed to drop more than 3% from baseline, and if shortness of breath occurred, breaks were taken, using diaphragmatic breathing during the breaks.

[0062] A course of interval normobaric hypoxic therapy combined with hydrogen inhalation consisted of 21 sessions. In each session, study participants alternated between hypoxic (7 min) and normoxic (7 min) mixtures. At the 3rd minute, inhalational hydrogen was added to the hypoxia regimen through a special cannula; the exposure duration was 60 minutes. Oxygen concentration was gradually reduced, provided that key physiological parameters stabilized. During the first week (7 days)—7 sessions, every other day—the oxygen content in the hypoxic gas mixture was at least 16%. In the second week, beginning on the 8th day of hypoxic training, the oxygen concentration in the mixture was reduced to -13%, then to 11% for the remaining seven days. Hypoxic training must be conducted in the first half of the day, before 13:00, to achieve maximum sensitivity of the subjects' bodies to hypoxia.

[0063] To monitor the effectiveness of the rehabilitation, measurements of heart rate (HR), respiratory rate (RR) and SpO2 (pulse oximeter Aiqura AD-805, manufactured in China) and OC (oxidative stress) were used using a portable analyzer FORM Plus, which allows for quantitative rapid determinations in whole blood samples (measured the content of free radicals (FORT test), total antioxidant capacity (FORD test) before, during and after the course.

[0064] Table 1 presents statistical data on the dynamics of heart rate, saturation (SpO2), respiratory rate (RR), and oxidative stress indicators (FORD). Statistical processing of the results was performed in accordance with the rules of mathematical statistics using Microsoft Excel and Statistica 6.0 for Windows. Paired and unpaired Student's t-tests were used for parametric analysis. All numerical data were presented as the arithmetic mean and standard error of the mean (M ± t). Differences were considered statistically significant at p < 0.05 (Table 1).

[0065] A reliable positive dynamics of the heart rate and SpO2 indicators was determined, in connection with which it was decided to use them directly as biofeedback indicators.

[0066] Table 2. Analysis of the dynamics of physiological parameters of subjects

[0067] - the differences are significant compared to the data before hypoxic therapy and treatment at p<0.05.

[0068] FORD values ​​were analyzed in samples taken from 25 subjects. FORT values ​​after exposure were 2.14 ± 0.12 mmol / L H2O2, which is significantly lower than before the training cycle, suggesting a pronounced antioxidant effect. Measuring the production of reactive oxygen species and the antioxidant capacity of the blood allows for a direct assessment of oxidative stress. Multiple linear regression analysis showed that heart rate (82.5), respiratory rate (16), SpO2 <98% (p < 0.001), and post-COVID-19 status were independent predictors of serum FORT values. FORT is a simple tool for assessing circulating ROS in routine clinical practice. Oxidative states are the main factors determining FORT values ​​in subjects who have recovered from COVID-19.

[0069] Preliminary experimental studies have shown that the hypoxia + hydrogen therapy regimen (60-minute exposure) used in training rabbits has more pronounced antioxidant effects compared to the traditional hypoxic-normoxic interval training regimen. Diene conjugates and malondialdehyde are used as quantitative markers for lipid peroxidation. Changes in antioxidant protection were observed due to changes in the reaction of catalase and superoxide dismutase (SOD) enzymes. The studies were conducted on male rabbits weighing 2.3-3 kg. The effect of interval hypoxic-normoxic training + hydrogen therapy was modeled using the Hypo-Oxy hypoxic therapy device from Oxyterra (Russia). Hypoxic periods alternated with normoxic ones (21% O2). The exposure session lasted 60 minutes daily for 21 days in the morning (from 11 am to 1 pm). The control and experimental groups of animals included up to 10 individuals.

[0070] 1 - control group - 1 (no exposure)

[0071] 2 - hypoxia + hydrogen therapy

[0072] 3 - control group - 2 (no exposure)

[0073] 4 - traditional mode of interval hypoxic-normoxic training.

[0074] It was shown that after a three-day period of exposure, the concentration of diene conjugates (DC) increases by 35%, similar changes occur with malondialdehyde (MD). After a week-long cycle of exposure, it was noted that the concentration of DC decreased by 20% and MD - by 13% (P < 0.05). In addition, it was noted that the dynamics of the studied parameters further had a negative trend (Fig. 1 - Concentration of LPO in the blood plasma (nmol / ml) of rabbits under the influence of interval hypoxic-normoxic training in comparison with intact animals (k), nmol / ml). These changes can be associated with significant restructuring in the body of male rabbits, in particular metabolism, which are also closely interconnected with the circulatory, endocrine, immune systems and, as a consequence, with a change in the biochemical status of the body.

[0075] During the analysis of the concentration of lipid peroxidation products in the blood plasma of male rabbits, it was noted that on the first day of exposure there was a reliable increase in the lipid peroxidation level, but on the third day of training a significant decrease in diene conjugates by 45% and malondialdehyde by 11% (P < 0.05) was noted (Fig. 2 - Concentration of lipid peroxidation in the blood plasma (nmol / ml) of rabbits under the influence of interval hypoxic-normoxic training and hydrogen therapy in comparison with intact animals (k), nmol / ml). After a week of exposure, a tendency towards a decrease in lipid peroxidation products was observed, and two weeks after training, their concentration was equal to the initial level, thus, it returns to the normal level.

[0076] A qualitative analysis of the effect of IHT on lipid peroxidation processes was performed by studying the concentration of antioxidant enzymes in the blood plasma. It was noted that after a week of training, males showed a reliable increase in SOD (Fig. 3 - Activity of antioxidant enzymes in the blood plasma during a 21-day IHT cycle in male rabbits, U / ml) compared to the control by more than 1.5 times (P < 0.05). Then, after a two-week period, a decrease in the enzyme content by 25% compared to the previous value (after 7 days) was noted; on the 21st day and at the end of the course, the SOD content was equal to the control values. The content of the enzyme catalase in the blood was detected in trace amounts, but the highest concentration was noted after a week and a two-week period of exposure to IHT + B.The dynamics of increasing enzymatic activity may be caused by the activation of adaptive pathways, which occurs in the first days of exposure to IHT+B on the body and is reflected in an increase in the number of free-radical compounds that must be utilized by natural antioxidants.

[0077] In males, an increase in SOD activity was observed during the two-week IHT+B cycle; on day 21, a 20% decrease in SOD was shown compared to the previous measurement (Fig. 4 - Activity of antioxidant enzymes in blood plasma during a 21-day IHT+B cycle in male rabbits, U / ml), but the indicator exceeded the control values ​​by 35% (P < 0.05). Thus, the rate of catalase activity did not change statistically significantly.

[0078] Conclusion: Superoxide dismutase concentrations in male rabbits were shown to significantly increase on the third day of exposure to IHT + B, followed by a twofold decrease after a two-week period. Catalase activity also changed at seven-day intervals. Based on this study, hypoxic-normoxic interval training and hydrogen therapy (IHT + B) were found to be effective in vivo. This mechanism suggests that IHT + B exerts a therapeutic effect on living organisms, unlocking the body's powerful antioxidant reserves.

[0079] An analysis of the indicators determining the antioxidant activity of the body (FORD / FORT, malondialdehyde, diene conjugates) revealed positive dynamics in 97.5±5% of cases when using the proposed method of activating reserve capacities during the body's rehabilitation period.

[0080] INDUSTRIAL APPLICABILITY

[0081] The proposed method is a comprehensive approach aimed at enhancing the body's adaptive capacity and physical performance. Its key advantage is that it does not cause side effects, unlike many pharmacological drugs often used to achieve similar results. The presented method is based on non-invasive and drug-free principles, making it safer and more accessible to a wider range of people. Its primary goal is to quickly and effectively restore the body's functional reserves, which can be depleted by extreme physical and psychological stress.

[0082] It is important to note that “maximum permissible loads” can refer to different conditions:

[0083] * **Competition Preparation:** Athletes require maximum performance, and this method can be useful for rapid recovery after intense training.

[0084] * ^Extreme Conditions:** Firefighters, rescue workers, military personnel, and other people whose work involves risk and requires high levels of endurance can benefit greatly from this method.

[0085] * **Rehabilitation after injuries and respiratory diseases:** In some cases, this method can promote faster and more complete recovery after injuries and operations, and diseases of the upper respiratory tract.

[0086] This method increases adaptive capacity and restores the body's functional reserves by reducing the content of active oxygen forms and peroxidation products in the body, which was reflected in the studies above (the FORT values ​​after exposure were 2.14 ± 0.12 mmol / l H2O2, which is significantly lower than before the training cycle).

[0087] Conducted clinical studies confirm the effectiveness and safety of this method.

[0088] In real life, this method can be actively used to restore the human body after diseases such as COVID-19, and the combined use of hypoxia (IHT) with hydrogen therapy provides maximum benefit. Literature

[0089] 1. Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, Katsura K, Katayama Y, Asoh S, Ohta S. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med. 2007 Jun;13(6):688-94. doi: 10.1038 / nm1577

[0090] 2. Barancik M., Kura B., LeBaron T.W. et al. Molecular and cellular mechanisms associated with effects of molecular hydrogen in cardiovascular and central nervous sys- terns / / Antioxidants (Basel). 2020. V. 9. No 12. P. 1281. https: / / doi.org / 10.3390 / antiox9121281

[0091] 3. Mallet RT, Manukhina EB, Ruelas SS, Caffrey J L, Downey HF. Cardioprotection by intermittent hypoxia conditioning: evidence, mechanisms, and therapeutic potential. Am J Physiol Heart Circ Physiol. 2018 Aug 1;315(2):H216-H232. doi: 10.1152 / ajpheart.00060.2018.

[0092] 4. Garkavi L.Kh., Kvakina E.B., Kuzmenko T.C., Shikhlyarova A.I. Anti-stress reactions and activation therapy. Activation reaction as a path to health through self-organization processes. - Ekaterinburg: Filantrop, 2003. Part 2. 336 p.

[0093] 5. Bulletin of Experimental Biology and Medicine. 2009. Vol. 147. No. 4. P. 380-384 Lukyanova L.D., Germanova E.L., Kopaladze R.A.

Claims

CLAUSES OF THE INVENTION 1 . A method of adaptive and restorative impact on the human body with a hypoxic gas mixture, including continuous measurement of oxygen saturation and heart rate (HR) before and during the impact, while in the first half of the day, a hypoxic gas mixture with an oxygen concentration of up to 16% is supplied to the patient at a gas mixture supply rate of 45-52 l / min with an exposure of 3 minutes, when the saturation decreases to 80%, inhalation hydrogen is continuously supplied through a nasal cannula or mask, while the supply rate of the hypoxic gas mixture is reduced to 20 l / min with an exposure time of 5 to 10 minutes, automatically increasing the oxygen concentration to 21% until the oxygen saturation and HR reach their original values, while the duration of one cycle of exposure, including alternate inhalation of a hypoxic gas mixture and a mixture with hydrogen, is 40-60 minutes, one procedure consists of 4-5 cycles of exposure,10 to 21 procedures are carried out every other day.

2. The method according to paragraph 1, characterized in that the procedures are carried out using inhalers, in which the effect of a hypoxic gas mixture on the human body is carried out by breathing through a respiratory mask, in combination with the supply of inhalation hydrogen using a cannula.

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