A composition containing hydrogen gas that promotes parasympathetic nervous system dominance and induces stress reduction effects in a short time.

Abstract

Development of a hydrogen gas-containing composition aimed at promoting parasympathetic nervous system dominance in a short period of time (approximately 10 minutes), thereby reducing mental and physical stress and inducing relaxation. [Solution] A stress-reducing composition containing hydrogen gas as an active ingredient.

Description

Technical Field

[0001] The present invention relates to a composition containing hydrogen gas that dominantly activates the parasympathetic nervous system, reduces stress, and induces a relaxing effect in a short period of time. Background Art

[0002] Mental and physical stress is a problem faced by many people living in modern society. It is a serious daily problem not only for people with pathological mental and physical stress, but also for healthy individuals. It reduces the efficiency of social life and work, and also adversely affects interpersonal relationships.

[0003] When a stress response becomes chronic, vitality decreases and one loses energy. If this state becomes chronic without being resolved, one will develop irritability and anxiety. Ultimately, it affects social life, such as causing depressed mood and aversion to daily activities. Furthermore, if the stress response remains unimproved, it causes not only mental health disorders but also many other diseases.

[0004] A device capable of immediately measuring mental and physical stress in a short time of about one minute has been developed and approved as a medical device. An example thereof is the Body Checker from Medicore. This device is approved as a general medical device (Class I) specified controlled medical device.

[0005] This Body Checker device analyzes changes in finger heart rate cycle to evaluate mental and physical stress states and the balance of the autonomic nervous system in response to stress, thereby predicting the risk of stress-related diseases, cardiovascular diseases, and lifestyle-related diseases, and enabling continuous health management.

[0006] The autonomic nervous system consists of the sympathetic and parasympathetic nervous systems. The parasympathetic nervous system is the autonomic nervous system that is dominant mainly during rest, relaxation, and sleep. In other words, the parasympathetic nervous system is said to be in a state where mental and physical stress, especially mental stress, is reduced, and it is known to induce a relaxing effect. The parasympathetic nervous system has the function of resting the body and putting it into a mode that prioritizes recovery.

[0007] The parasympathetic nervous system plays a role in lowering blood pressure and heart rate, relaxing muscles, and suppressing sweating. It also plays a role in increasing intestinal peristalsis and urination.

[0008] Generally, increased sympathetic nervous system activity leads to decreased parasympathetic nervous system activity, and vice versa. Therefore, the ratio of the parasympathetic to sympathetic nervous systems can serve as an indicator of stress levels.

[0009] Stress coping ability (sense of coherence = SOC) is thought to consist of three abilities: "sense of comprehensibility," "sense of manageability," and "sense of meaningfulness." It refers to the ability of the human body to adapt appropriately to stress and maintain a stable state.

[0010] In particular, individuals who can find meaning and fulfillment in overcoming difficult situations—a sense of "meaningfulness"—tend to have a lower risk of developing dementia.

[0011] Cardiac stability refers to the electrical stability of the heart, and chronic stress can reduce this stability. The lower the stability, the higher the likelihood of developing heart disease.

[0012] To make the parasympathetic nervous system dominant, as mentioned above, improvements to daily life are necessary, and it is generally known that this takes a long time. For example, "(1) Get some sunlight for about 15 seconds when you wake up in the morning (2) Do some stretching or light exercise (3) If you have a late dinner, eat something light (4) Avoid using computers or smartphones before bed (5) If you feel stressed, take a deep breath (exhale the unpleasant things that happened today) (6) Try sleeping on your side or stomach rather than on your back (7) Listen to your favorite music and create some time to relax (8) Be careful with caffeine after sunset (9) Laugh often." https: / / smartdock.jp / contents / lifestyle / lh071 / page / 2 / This suggests that the parasympathetic nervous system can be made dominant through long-term lifestyle improvements.

[0013] If it were possible to activate the parasympathetic nervous system in a short time, such as 10 minutes, it would be possible to activate it during breaks at work, leading to immeasurable improvements in work efficiency.

[0014] Furthermore, if it shows results in a short time, it can be applied to a large number of people, and the benefits would be immeasurable.

[0015] It has been suggested that drinking hydrogen water (water with dissolved hydrogen gas; the molecular formula for hydrogen gas is H2) can help relieve fatigue and promote parasympathetic nervous system activity. However, this study has shown that 300 mL should be consumed twice a day for 7 weeks, and short-term effects have not been demonstrated (Non-Patent Literature 1).

[0016] In a study using rats, it has been suggested that inhaling hydrogen gas in a hypertensive rat model induced by kidney removal lowered blood pressure and promoted parasympathetic nervous system dominance. In this case, hydrogen gas inhalation was administered for one hour per day for four weeks (Non-Patent Literature 2).

[0017] Molecular hydrogen (molecular formula H2) was first reported as a therapeutic antioxidant (Non-Patent Literature 3). Subsequent studies have shown that hydrogen has multiple functions that are effective against various disease models. Hydrogen gas has been reported to have various benefits for stroke, myocardial infarction, chronic obstructive pulmonary disease, cancer, and COVID-19 in elderly patients. Because hydrogen can cross the blood-brain barrier by diffusion and reach the brain and nerves, it is expected that hydrogen may exert some effect on the nervous system.

[0018] In patients who have suffered a stroke, inhaling 3% hydrogen gas has been shown to improve clinical symptoms, brain MRI results, and rehabilitation effectiveness compared to control patients. However, this is based on the observation that the inhalation was performed twice a day for one hour each day for seven days (Non-Patent Literature 4).

[0019] Furthermore, in patients who experienced out-of-hospital cardiac arrest and whose heartbeat was restored, inhaling a gas containing 2% hydrogen gas reduced mortality and restored neurological function. However, this was reported to be the case only when hydrogen gas inhalation was continued for 18 hours (Non-Patent Literature 5).

[0020] It has been reported that inhaling 3% hydrogen gas for six months can improve the condition of Alzheimer's disease patients and maintain the effectiveness of subsequent treatment (Non-Patent Literature 6).

[0021] While the effects of hydrogen gas inhalation have been investigated in animal experiments, these studies generally involve administering a gas containing hydrogen for one hour to examine its effects (Non-Patent Literature 3), and no results have been found for short-term administration of 10 minutes.

[0022] In other words, while hydrogen gas inhalation has been shown to have various effects, there are no reports of effects being observed in such a short period as 10 minutes, and it is not expected that the company in question would produce any effect on the nervous system from a short 10-minute hydrogen gas inhalation. [Prior art documents] [Non-patent literature]

[0023] [Non-Patent Document 1] Mizuno, K. et al. Hydrogen-rich water for improvements of mood, anxiety, and autonomic nerve function in daily life Med Gas Res 2018:22;7(4):247-255.) [Non-Patent Document 2] Suga, K., et al. Daily inhalation of hydrogen gas has a blood pressure-lowering effect in a rat model of hypertension. Sci Rep. 2020:26;10:20173) [Non-Patent Document 3] Ohsawa I, et al.: Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med. 2007; 13: 688-694. [Non-Patent Document 4] Ono, H. et al., Hydrogen Gas Inhalation Treatment in Acute Cerebral Infarction: A Randomized Controlled Clinical Study on Safety and Neuroprotection. J. Stroke. Cerebrovascul Dis. 2017: 26; 2587-2594 ) [Non-Patent Document 5] Tomura, T. et al. Efficacy of inhaled hydrogen on neurological outcome following brain ischaemia during post-cardiac arrest care (HYBRID II): a multi-centre, randomised, double-blind, placebo-controlled trial. eClinicalMedicine. 2023; 58;101907. [Non-Patent Literature 6] Ono, H. Therapeutic Inhalation of Hydrogen Gas for Alzheimer’s Disease Patients and Subsequent Long-Term Follow-Up as a Disease-Modifying Treatment: An Open Label Pilot Study. Pharmaceuticals 2023, 16(3), 434 Summary of the Invention Problem to be Solved by the Invention

[0024] An object of the present invention is to develop a composition that makes the parasympathetic nervous system dominant within a short period of about 10 minutes, improves mental and physical stress, and exerts a relaxing effect. Means for Solving the Problem

[0025] The present inventor examined items including sympathetic nerve index, parasympathetic nerve index, stress coping ability, mental stress reduction degree, heart stability, fatigue reduction degree, physical stress reduction degree, and vascular condition in subjects using Medicore's Body Checker, had the subjects inhale hydrogen gas for 10 minutes in a room filled with 2 to 4% hydrogen gas, immediately re-measured the aforementioned items using the Body Checker, and measured the changes in these items.

[0026] By analyzing these changes in 21 subjects, we found statistically significant changes or trends, which led to the completion of the present invention.

[0027] In other words, the present invention is as follows. [1] A stress-reducing composition containing hydrogen gas as an active ingredient. [2] The composition of [1], which reduces mental and physical stress and induces a relaxing effect with a short inhalation time of about 10 minutes. [3] A composition of [1] or [2] that, with a short inhalation time of about 10 minutes, statistically significantly increases or improves the parasympathetic / sympathetic ratio, stress coping ability, cardiac stability, and overall score. [4] A stress-reducing device including a hydrogen gas supply unit for causing a subject to inhale a stress-reducing composition containing hydrogen gas as an active ingredient. [5] A device of [4] that, with a short inhalation time of about 10 minutes, tends to increase and improve parasympathetic nervous system indicators and the degree of physical stress reduction. [6] The apparatus of [4] or [5] that allows for the inhalation of 2-4% hydrogen gas for 10 minutes. [7] A device whose main body is made of cypress wood, one of the devices described in [4] to [6]. [Effects of the Invention]

[0028] Inhaling hydrogen gas for 10 minutes statistically significantly increased and improved the parasympathetic / sympathetic nervous system ratio, stress coping ability, cardiac stability, and overall score. Parasympathetic nervous system indicators and the degree of physical stress reduction tended to increase or improve. [Brief explanation of the drawing]

[0029] [Figure 1] This figure shows a device (cabinet) for administering hydrogen gas to a patient. [Figure 2] This figure shows a device for administering hydrogen gas to a patient. [Modes for carrying out the invention]

[0030] The present invention will be described in detail below. The present invention relates to a composition containing hydrogen gas that promotes parasympathetic nervous system dominance and induces stress reduction effects in a short period of time. Furthermore, the present invention relates to a composition containing hydrogen gas that statistically significantly increases and improves the parasympathetic / sympathetic nervous system ratio, stress coping ability, cardiac stability, and overall score.

[0031] The composition of the present invention can reduce mental and physical stress and induce a relaxing effect. Specifically, the present invention is a stress-reducing composition containing hydrogen gas as an active ingredient. This composition can promote parasympathetic nervous system dominance and statistically significantly increase and improve the parasympathetic / sympathetic nervous system ratio, stress coping ability, cardiac stability, and overall score. Furthermore, the above composition can reduce mental and physical stress and induce a relaxing effect. Moreover, the composition of the present invention can tend to increase and improve parasympathetic nervous system indicators and the degree of physical stress reduction.

[0032] The concentration of hydrogen gas in the composition containing the hydrogen gas of the present invention as an active ingredient is 1-4% (v / v), preferably 2.5-3.5% (v / v), and more preferably about 3% (v / v). While it is desirable for the hydrogen gas content to be less than about 4% (v / v) to ensure safety, a higher hydrogen gas content is possible under safe conditions where static electricity is not generated under sealed conditions. The composition containing the hydrogen gas of the present invention as an active ingredient may further contain oxygen gas and / or other inert gases. If oxygen gas is included, it consists of a mixture of hydrogen gas and oxygen gas. The oxygen gas is consumed for respiration. The concentration of oxygen gas is 10-30% (v / v), preferably 15-25% (v / v), and more preferably 21% (v / v). As the inert gas, nitrogen gas, helium gas, argon gas, etc., can be used, but inexpensive nitrogen gas is preferred. The content of this inert gas can be arbitrarily set by those skilled in the art, as long as it is not excessive, but considering the oxygen gas concentration for respiration, 80% (v / v) or less is preferable. Furthermore, the composition containing hydrogen gas as an active ingredient of the present invention may be a mixture of hydrogen gas and air. Such a mixture can be easily produced by appropriately mixing hydrogen gas with air. Furthermore, the composition containing hydrogen gas as an active ingredient of the present invention may also contain an anesthetic gas. In this case, the composition containing hydrogen gas as an active ingredient consists of a mixture of hydrogen gas and an anesthetic gas. Examples of anesthetic gases include nitrous oxide.

[0033] In the embodiments described later, the hydrogen gas source used was hydrogen gas obtained by the electrolysis of water, but the method of generating hydrogen is not limited to electrolysis.

[0034] The composition containing hydrogen gas as an active ingredient of the present invention can be placed in a pressure-resistant container such as a gas cylinder. Alternatively, a device that generates hydrogen gas by electrolysis of water may be used. The present invention also encompasses containers containing compositions containing hydrogen gas as an active ingredient.

[0035] The composition of the present invention, which contains gaseous hydrogen gas as an active ingredient, can be inhaled by a test subject.

[0036] The method of inhalation of hydrogen gas is not limited, as it can be inhaled using a medical mask, a similar mask, or a nasal cannula.

[0037] For example, inhalation can be performed using an inhalation device, which may involve inhaling a composition containing hydrogen gas as an active ingredient from a container through piping via the inhalation device. The inhalation device is not limited, but examples include an inhalation mask, which preferably covers the patient's mouth and nose simultaneously.

[0038] The methods described above can sometimes create a feeling of confinement and cause stress due to discomfort; therefore, it is even more desirable to inhale hydrogen in a space filled with a constant 2-4% hydrogen concentration within a cabinet. Furthermore, inhaling hydrogen gas from a small space has the advantage of allowing inhalation of gas with a stable hydrogen gas concentration.

[0039] Since stress sensors are also present in the skin, it is desirable to place the body in a space filled with hydrogen and absorb it not only through inhalation via the lungs but also through the skin, but this is not the only option.

[0040] In other words, for example, there is a sealed small chamber as an inhalation means, the chamber being large enough for a patient to enter, and the patient can inhale the hydrogen gas by supplying a composition containing the hydrogen gas of the present invention as an active ingredient into the chamber while the patient is inside. An example of such a small chamber is a sealed small chamber equipped with a chair. Figure 1 shows an example of such a small chamber. The small chamber can be made of, for example, cypress wood. The small chamber is equipped with a hydrogen generator, which supplies hydrogen gas into the small chamber through a pipe. For example, it may be installed under a chair. The hydrogen generator may be a hydrogen gas cylinder or a generator that generates hydrogen by electrolysis of pure water. Examples of such hydrogen generators include the QL-H600T multi-functional hydrogen generator and the OPGU-2100 (HORIBA). An example of a small chamber equipped with a hydrogen generator is the "H2 Hydrogen and Cypress Small Room" (manufactured by Shigiyama Furniture Industry Co., Ltd., sold by Mytos Co., Ltd.). Another example of the above-mentioned small chamber is a bed. The patient can inhale a composition containing hydrogen gas as an active ingredient while lying down in bed.

[0041] Furthermore, the present invention includes an apparatus for supplying a composition containing hydrogen gas as an active ingredient to a subject, comprising a container containing a composition containing hydrogen gas as an active ingredient, a means for gas inhalation, and a supply pipe for supplying the gas in the container to the means for inhalation. The container is, for example, a hydrogen gas cylinder. The means for gas inhalation includes, as mentioned above, an inhalation mask and a sealed chamber. The apparatus may further include a container containing at least one gas selected from the group consisting of oxygen gas, inert gas, air, and anesthetic gas. In this case, the composition containing hydrogen gas as an active ingredient and at least one gas selected from the group consisting of oxygen gas, inert gas, and air may be supplied to the means for gas inhalation separately or mixed together. For example, a gas inhalation bag containing hydrogen gas may be directly connected to an inhalation mask, and hydrogen gas may be supplied to this gas inhalation bag from a gas cylinder containing hydrogen gas. Figure 2 shows a schematic diagram of the apparatus of the present invention. The figure shows a gas inhalation device 1, a container 2 containing hydrogen gas as an active ingredient, a container 3 containing at least one gas selected from the group consisting of oxygen gas, inert gas, air, and anesthetic gas, and piping 4, wherein the gas is supplied to the gas inhalation device through the piping and administered to the patient.

[0042] The composition containing hydrogen gas as an active ingredient is administered for 5 to 15 minutes, preferably 8 to 12 minutes, and more preferably 10 minutes. It can be administered 1 to 5 times per day, preferably 1 to 3 times, and more preferably 2 times. The administration can be carried out for 1 to 30 days, preferably 5 to 20 days, and more preferably 7 to 14 days. The inhalation speed when administering hydrogen gas is, for example, 6 to 10 L per minute, preferably about 8 L per minute.

[0043] To determine whether inhaling a composition containing hydrogen gas as an active ingredient of the present invention has a stress-reducing effect, the degree of stress before and after inhalation of hydrogen gas should be measured. Stress measurement equipment can be used for this measurement. Stress measurement equipment includes PhotoPlethystemograph (PPG) and Accelerated Photoplethysmograph (APG) devices that measure stress. A pulse wave is a waveform recording of the pulsations of the chest wall and major blood vessels caused by the heartbeat. The changes in arterial wave patterns, caused by fluctuations in vascular wall pressure and vascular diameter due to the cardiac cycle, are transmitted peripherally, and these changes are called pulse waves. The primary purpose of pulse wave analysis is to observe the mechanical movement and hemodynamics of the heart, and it is a waveform representation of the pulsations of the chest wall and major blood vessels caused by the heartbeat. APG is a pulse wave examination method that reveals the degree of vascular aging by analyzing the waveform obtained by second-degree differentiation of the fingertip volume pulse wave waveform. An example of a stress measurement device is BodyChecker neo (Tokyo Iken Co., Ltd.). Using such measuring devices, the average heart rate, sympathetic nervous system index, parasympathetic nervous system index, parasympathetic / sympathetic nervous system ratio, stress coping ability, degree of mental stress reduction, cardiac stability, degree of fatigue reduction, degree of physical stress reduction, vascular stage, peripheral vascular elasticity, arterial vascular elasticity, and vascular age can be measured, and the presence or absence of stress reduction effects can be determined based on these measured values. Furthermore, the presence or absence of stress reduction effects can be determined by a comprehensive score based on these indicators.

[0044] For example, inhaling hydrogen gas for 10 minutes statistically significantly increases and improves the parasympathetic / sympathetic nervous system ratio, stress coping ability, cardiac stability, and overall score. Furthermore, parasympathetic nervous system indicators and physical stress reduction levels increase and improve. For instance, sympathetic nervous system indicators decrease by 20% or more, preferably 30% or more, while parasympathetic nervous system indicators increase by 5% or more, preferably 10% or more. Stress coping ability increases by 5% or more, preferably 10% or more, and more preferably 20 points or more. Cardiac stability also increases by 5% or more, preferably 10% or more, and more preferably 20 points or more. In particular, improving the parasympathetic / sympathetic nervous system ratio is crucial for stress reduction; inhaling hydrogen gas for 10 minutes results in a parasympathetic / sympathetic nervous system ratio of 1 or more, preferably 1.1 or more, and more preferably 1.2 or more, with the ratio increasing by 20% or more, preferably 30% or more, and more preferably 40% or more.

[0045] These results suggest that inhaling hydrogen gas reduces stress and induces relaxation. [Examples]

[0046] The present invention will be specifically described by the following embodiments, but the present invention is not limited to these embodiments. Many devices have been developed for measuring the parasympathetic nervous system, and the method is not limited.

[0047] [Examples] The subjects were participants in the 2024 Tokyo Big Sight exhibition (6th Sports Science Technology Expo, July 16-18, 2024), who wished to inhale hydrogen gas and wanted to know the results of measuring its effects using Body Checker, and who agreed to provide the data.

[0048] The subjects excluded were four individuals who scored 85 or higher overall, or whose parasympathetic nervous system index was 2 or higher, indicating that further hydrogen gas inhalation benefits were not expected.

[0049] The hydrogen gas generator used was a Sunmore hydrogen gas generator (QL-H600T multi-functional hydrogen generator), but it is not limited to this model.

[0050] The hydrogen gas concentration inside the cabinet was measured with a hydrogen gas meter and was 2-4% (v / v). However, since the effective hydrogen concentration is generally 1% (v / v) or higher, the hydrogen gas concentration is not limited to 2-4% (v / v).

[0051] Figure 1 shows a photograph, size, and weight of a small room made of cypress wood (H2 hydrogen and cypress room MITOS HydroOasisPremium). The user spends 10 minutes in this room, absorbing hydrogen through the lungs and skin. However, this is not the only method; the important thing is to introduce hydrogen gas into the body.

[0052] While hydrogen gas inhalation time is not limited to 10 minutes, 5 to 15 minutes is preferable, and 8 to 12 minutes is more preferable.

[0053] Statistical testing was performed using the analysis methods built into Excel. A t-test was used, assuming a single-arm test and heteroscedasticity of the sample. Results with a p-value of 0.05 or less were considered statistically significant, and results with a p-value of 0.1 or less were considered to indicate a statistically significant trend.

[0054] Table 1 summarizes the changes before and after hydrogen inhalation and the results of statistical analysis. Table 1 shows the analysis results for 21 subjects. Vascular age closely matches chronological age, indicating the accuracy of the measurement method.

[0055] [Table 1]

[0056] The results showed that inhaling hydrogen gas for 10 minutes statistically significantly increased or improved the parasympathetic / sympathetic nervous system ratio, stress coping ability, cardiac stability, and overall score. Parasympathetic nervous system indicators and the degree of physical stress reduction tended to increase or improve. [Industrial applicability]

[0057] Compositions containing hydrogen gas as an active ingredient reduce stress and induce a relaxing effect. By inhaling a composition containing hydrogen gas for about 10 minutes during work breaks, fatigue can be relieved and refreshed. By inhaling a hydrogen gas-containing composition for about 10 minutes during work breaks, it is possible to improve work efficiency, reduce stress between people, and live a more comfortable life. [Explanation of symbols]

[0058] 1. Means for gas inhalation 2. Containers containing hydrogen gas 3. A container containing at least one gas selected from the group consisting of oxygen gas, inert gas, air, and anesthetic gas. 4 Piping

Claims

1. A stress-reducing composition containing hydrogen gas as an active ingredient.

2. The composition according to claim 1, which reduces mental and physical stress and induces a relaxing effect with a short inhalation time of about 10 minutes.

3. The composition according to claim 1, which, with a short inhalation time of about 10 minutes, statistically significantly increases or improves the parasympathetic / sympathetic nervous system ratio, stress coping ability, cardiac stability, and overall score.

4. A stress reduction device including a hydrogen gas supply unit for causing a subject to inhale a stress reduction composition containing hydrogen gas as an active ingredient.

5. The apparatus according to claim 4, which, with a short inhalation time of about 10 minutes, tends to increase and improve parasympathetic nerve indicators and the degree of physical stress reduction.

6. The apparatus according to claim 4, which enables inhalation of 2-4% hydrogen gas for 10 minutes.

7. The apparatus according to claim 4, wherein the main body is made of cypress wood.

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