Hydrogen-containing inhalation-type pharmaceutical composition for preventing, ameliorating or treating cognitive dysfunction

Abstract

The present invention relates to an inhalation-type pharmaceutical composition for preventing, ameliorating or treating cognitive impairment containing hydrogen. The inhalation-type pharmaceutical composition of the present invention contains hydrogen, and can prevent, ameliorate or treat cognitive impairment by inhibiting the production of nitric oxide and the accumulation of reactive oxygen species due to oxidative stress in nerve cells. In addition, the composition can induce generation of nerve growth factors such as a brain-derived neurotrophic factor, a fibroblast growth factor 2, an insulin-like growth factor 1, an octamer binding transcription factor 4, a brain dopamine neurotrophic factor, a midbrain astrocyte-derived neurotrophic factor, a transforming growth factor beta 1 and a placental growth factor.

Description

Technical Field

[0001] The present invention relates to an inhaled pharmaceutical composition containing hydrogen for preventing, improving or treating cognitive dysfunction. Background Art

[0002] Recently, research is being conducted on substances that react using hydrogen as a reducing agent for active oxygen in the body and develop them for medical use.

[0003] In particular, as modern people's diets change, oxygen inhaled into the human body is incompletely burned and converted into active oxygen, which has become a cause of accelerating human aging and inducing diseases. When hydrogen is inhaled into the human body as an antioxidant, it combines with active oxygen and is converted into harmless water, which is a substance that can excrete active oxygen through urine and sweat.

[0004] On the other hand, cognitive dysfunction is a problem that occurs during the accident process. It is a concept that includes loss of reasoning ability, amnesia, learning disabilities, attention problems, decreased intelligence, and other mental function reductions. Cognitive dysfunction may occur during fetal development, during delivery, after delivery, or due to diseases that occur at any time in life. It may be unexplained in newborns or young children. The initial causes of cognitive dysfunction are chromosomal abnormalities and hereditary syndromes, malnutrition, exposure to drugs before delivery, heavy metal pollution such as lead, hypoglycemia,

[0005] Neonatal jaundice, hypothyroidism, trauma or abuse, low oxygen levels in the uterus, difficult labor or premature birth, etc.

[0006] Dementia, a representative disease of cognitive dysfunction, is a disease phenomenon different from normal aging and is classified according to the cause into Alzheimer's disease, vascular dementia, other dementias caused by alcoholism, dementia caused by trauma, dementia caused by sequelae of Parkinson's disease, and the like.

[0007] However, the preventive, ameliorative, or therapeutic effects of hydrogen on cognitive impairment are still unknown, and there is a need for a system that supplies hydrogen at a specified concentration to patients, etc., for medical use.

[0008] Prior art literature

[0009] Patent Literature

[0010] Korean Patent No. 10-1344047 (granted on December 16, 2013) Summary of the invention

[0011] Therefore, the present inventors have made many efforts to study gaseous inhalation compositions that can prevent, improve or treat cognitive dysfunction, and found that gaseous compositions containing hydrogen can inhibit the generation and inflammation of oxidative stress (reactive oxygen species (ROS)) and nitric oxide species (NOS) in nerve cells and tissues and induce nerve growth factor, thereby completing the present invention.

[0012] Therefore, the object of the present invention is to provide a pharmaceutical composition for inhalation of molecular hydrogen (H2) gas state that can prevent, improve or treat cognitive dysfunction, but it is not limited to this. Ordinary technicians in the technical field to which the present invention belongs can clearly understand other purposes not mentioned through the following description.

[0013] The present invention provides an inhaled pharmaceutical composition containing hydrogen for preventing, improving or treating cognitive dysfunction.

[0014] The content of the hydrogen in the total composition may be 1 weight percent to 5 weight percent.

[0015] The cognitive dysfunction may be dementia, Parkinson's disease, Binswanger's disease, learning disabilities, mild cognitive impairment, Pick's disease, agnosia, amnesia, aphasia, apraxia or delirium.

[0016] The composition can inhibit the generation of nitric oxide (NO) and the accumulation of reactive oxygen species caused by oxidative stress in nerve cells.

[0017] The above-mentioned composition can induce the production of one or more nerve growth factors selected from the group consisting of brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF-2), insulin-like growth factor 1 (IGF-1), octamer-binding transcription factor 4 (Oct4), mesencephalic astrocyte-derived Neurotrophic Factor (MANF), transforming growth factor β1 (TGFB1) and placental growth factor (PIGF).

[0018] The composition can inhibit the generation of β-amyloid protein (Aβ) and reduce the expression of Tau protein.

[0019] On the other hand, the above-mentioned inhalation pharmaceutical composition can be prepared by a system including the following parts: a hydrogen generation module, which generates hydrogen by electrolyzing water; a hydrogen storage tank, which is connected to the above-mentioned hydrogen generation module, receives the hydrogen generated from the above-mentioned hydrogen generation module and stores the received hydrogen; a hydrogen flow regulating unit, which is connected to the above-mentioned hydrogen storage tank, and regulates the flow of hydrogen discharged from the above-mentioned hydrogen storage tank; an air storage tank, which receives air supplied from the outside and stores the received air; an air flow regulating unit, which is connected to the above-mentioned air storage tank, and regulates the flow of air discharged from the above-mentioned air storage tank; a gas mixing unit, which is connected to the above-mentioned hydrogen storage tank to allow the hydrogen discharged from the above-mentioned hydrogen storage tank to flow in, and is connected to the above-mentioned air storage tank to allow the air discharged from the above-mentioned air storage tank to flow in, and mixes the inflowing hydrogen with the air internally; and a control module, which controls the operation of the above-mentioned hydrogen flow regulating unit and the above-mentioned air flow regulating unit.

[0020] Furthermore, the present invention provides a hydrogen mixed gas generating system, characterized in that the above-mentioned hydrogen storage tank includes a hydrogen flow path inside for flowing the hydrogen received from the above-mentioned hydrogen generating module, and in the process of flowing the hydrogen through the above-mentioned hydrogen flow path, water contained in the hydrogen is separated and the separated water is discharged to the outside.

[0021] Furthermore, the present invention provides a hydrogen mixed gas generating system, characterized in that the above-mentioned air storage tank includes: a main body shell, which forms an air flow space inside; and a plurality of partition components, each of which is provided with a flow hole formed in a manner to allow air to pass through, and is arranged at specified intervals from each other along the length direction of the above-mentioned main body shell in the air flow space of the above-mentioned main body shell.

[0022] Furthermore, the present invention provides a hydrogen mixed gas generating system, characterized in that the above-mentioned hydrogen flow regulating unit includes: a hydrogen flow regulating valve, regulating the flow rate of hydrogen discharged from the above-mentioned hydrogen storage tank and supplied to the above-mentioned gas mixing unit; a hydrogen flow measuring instrument, measuring the flow rate of hydrogen supplied to the above-mentioned gas mixing unit; and a hydrogen pressure regulating valve, regulating the flow rate of hydrogen discharged from the above-mentioned hydrogen storage tank to the outside in order to regulate the pressure inside the above-mentioned hydrogen storage tank.

[0023] Furthermore, the present invention provides a hydrogen mixed gas generating system, characterized in that the above-mentioned air flow regulating unit includes: an air flow regulating valve, which regulates the flow rate of air discharged from the above-mentioned air storage tank and supplied to the above-mentioned gas mixing unit; an air flow measuring instrument, which measures the flow rate of air supplied to the above-mentioned gas mixing unit; and an air pressure regulating valve, which regulates the flow rate of air discharged from the above-mentioned air storage tank to the outside in order to regulate the pressure inside the above-mentioned air storage tank.

[0024] The inhalation pharmaceutical composition of the present invention contains hydrogen, and can prevent, improve or treat cognitive dysfunction by inhibiting the generation of nitric oxide and the accumulation of reactive oxygen species caused by oxidative stress in nerve cells.

[0025] Furthermore, the composition of the present invention can induce the production of one or more nerve growth factors selected from the group consisting of brain-derived neurotrophic factor, fibroblast growth factor 2, insulin-like growth factor 1, octamer-binding transcription factor 4, brain dopamine neurotrophic factor (CDNF, Cerebral Dopamine Neurotrophic Factor), midbrain astrocyte-derived neurotrophic factor, transforming growth factor β1 and placental growth factor.

[0026] Furthermore, the system disclosed in the present invention has the effect of being able to stably generate a hydrogen mixed gas in which hydrogen and air are mixed at a predetermined ratio. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 FIG. 1 is a structural diagram showing the overall structure of a hydrogen mixed gas generating system according to an embodiment of the present invention.

[0028] Figure 2 This is a structural diagram showing a part of the structure including a hydrogen generation module, a hydrogen storage tank and a hydrogen flow regulating unit of a hydrogen mixed gas generation system according to an embodiment of the present invention.

[0029] Figure 3 A diagram showing the detailed structure of a hydrogen gas storage tank of a hydrogen mixed gas production system according to an embodiment of the present invention.

[0030] Figure 4 This is a structural diagram showing a part of the structure including an air tank and an air flow regulating unit of a hydrogen mixed gas generating system according to an embodiment of the present invention.

[0031] Figure 5 It is a three-dimensional view showing the overall structure of an air storage tank of a hydrogen mixed gas generating system according to an embodiment of the present invention.

[0032] Figure 6 It is a cutaway perspective view showing the overall structure of an air storage tank of a hydrogen mixed gas generating system according to an embodiment of the present invention.

[0033] Figure 7 It is an exploded perspective view showing the overall structure of an air storage tank of a hydrogen mixed gas generating system according to an embodiment of the present invention.

[0034] Figure 8 The invention is a perspective view showing a first shell of an air storage tank of a hydrogen mixed gas generating system according to an embodiment of the present invention.

[0035] Fig. 9It is a perspective view showing a second shell of an air storage tank of a hydrogen mixed gas generating system according to an embodiment of the present invention.

[0036] Fig.10 It is a cutaway perspective view showing the overall structure of an air storage tank of a hydrogen mixed gas generating system according to an embodiment of the present invention.

[0037] Fig.11 It is a side sectional view showing the overall structure of an air storage tank of a hydrogen mixed gas generating system according to an embodiment of the present invention.

[0038] Fig.12 It is a three-dimensional view showing a multi-hole partition member and a single-hole partition member of an air storage tank of a hydrogen mixed gas generation system according to an embodiment of the present invention.

[0039] Fig.13 The results are from a clinical study in which participants were asked to measure the blood levels of total intracellular reactive oxygen species (ROS) and nitric oxide (NO) before and after inhaling a hydrogen gas mixture.

[0040] Fig.14 The results are from a clinical study in which participants were asked to measure serum brain-derived neurotrophic factor (BDNF) levels before and after inhaling a hydrogen gas mixture.

[0041] Fig.15 The results are from a clinical study in which participants were asked to measure total intracellular β-secretase 1 (BACE-1) concentrations before and after inhalation of a hydrogen gas mixture.

[0042] Fig.16 The results are the results of measuring the serum levels of amyloid β (Aβ) and Tau protein before and after inhalation of hydrogen mixed gas in participants of a clinical study.

[0043] Fig.17 The results are the results of measuring the serum concentrations of monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and vascular endothelial growth factor A (VEGF-A) before and after inhalation of hydrogen mixed gas in participants of a clinical study.

[0044] Description of reference numerals:

[0045] 100: Hydrogen generation module

[0046] 110: Water tank

[0047] 130: Electrolyzer

[0048] 150: Electrolytic plate

[0049] 170: Oxygen tank

[0050] 200: Hydrogen storage tank

[0051] 210: Tank body

[0052] 230: Hydrogen flow inlet

[0053] 250: Hydrogen flow path

[0054] 270: Drain

[0055] 290: Hydrogen supply port

[0056] 300: Hydrogen flow regulation unit

[0057] 310: Hydrogen flow control valve

[0058] 330: Hydrogen flow meter

[0059] 350: Hydrogen pressure regulating valve

[0060] 400: Air tank

[0061] 410: Body shell

[0062] 420: Partition components

[0063] 500: Air flow adjustment unit

[0064] 510: Air flow control valve

[0065] 530: Air flow measuring instrument

[0066] 550: Air pressure regulating valve

[0067] 600: Control module

[0068] 700: Gas mixing unit

[0069] 800: Mixed gas sterilization department DETAILED DESCRIPTION

[0070] Hereinafter, the present invention will be described in detail. Prior to this, the terms or words used in this specification and the scope of protection of the invention should not be interpreted in a limited manner to the usual or dictionary meanings, but should be interpreted from the perspective that the inventor can appropriately define the concept of the term in order to explain his invention in the best way, as the meaning and concept that conforms to the technical idea of ​​the present invention. Therefore, the structure described in the embodiments described in this specification is only the most preferred embodiment of the present invention, and does not fully represent the technical idea of ​​the present invention. It should be understood that at the time of filing this application, there may also be a variety of equivalents and modifications that can replace them.

[0071] The present invention features an inhaled pharmaceutical composition comprising hydrogen for preventing, improving or treating cognitive dysfunction.

[0072] The composition exists in a gaseous state that can be inhaled by humans, and contains hydrogen, and the hydrogen is molecular hydrogen (H2).

[0073] The content of hydrogen in the total composition may be 1 to 5 weight percent, preferably 2 to 3 weight percent.

[0074] The gas components other than hydrogen in the above composition may be composed of filtered air, preferably, may contain 95 weight percent to 99 weight percent, more preferably, may contain 97 weight percent to 98 weight percent.

[0075] On the other hand, the above-mentioned cognitive dysfunction refers to a disease in which cognitive functions such as memory processing, perception and problem solving cannot be performed, and more specifically refers to symptoms such as dementia, Parkinson's disease, Binswanger disease, learning disorder, Pick's disease, agnosia, amnesia, aphasia, apraxia, or delirium.

[0076] The composition can inhibit the generation of nitric oxide and the accumulation of reactive oxygen species caused by oxidative stress in nerve cells.

[0077] Furthermore, the composition can induce the production of nerve growth factor, and the nerve growth factor can be selected from the group consisting of brain-derived neurotrophic factor, fibroblast growth factor 2, insulin-like growth factor 1, octamer-binding transcription factor 4, midbrain astrocyte-derived neurotrophic factor, transforming growth factor β1, and placental growth factor.

[0078] The above composition can be administered to a patient by inhalation via a nasal cannula, etc., and can be provided for 1 to 100 minutes per day for 1 to 100 days, preferably, for 10 to 60 minutes per day for 10 to 50 days.

[0079] On the other hand, the inhalation pharmaceutical composition for preventing, improving or treating cognitive dysfunction can be prepared by a system that generates a hydrogen mixed gas by mixing hydrogen gas and air.

[0080] The above-mentioned system may include a hydrogen generation module 100, a hydrogen storage tank 200, a hydrogen flow regulating unit 300, an air storage tank 400, an air flow regulating unit 500, a control module 600, a gas mixing unit 700 and a mixed gas sterilization unit 800. The hydrogen mixed gas generation system according to one embodiment of the present invention can stably generate a hydrogen mixed gas that maintains a specified mixing ratio of hydrogen and air.

[0081] Below, refer to Figures 1 to 12 The various structures of the hydrogen mixed gas generating system according to one embodiment of the present invention will be described in detail.

[0082] First, the hydrogen generation module 100 is provided in such a manner as to generate hydrogen by electrolyzing water.

[0083] As an example, Figure 2 As shown, the hydrogen generation module 100 may include: a water tank 110, which is arranged in a manner that water flows in from the outside; an electrolyzer 130, which receives water from the water tank 110; an electrolysis plate 150, which includes an oxygen electrode plate, an electrolysis separation membrane, and a hydrogen electrode plate, and electrolyzes the water in the electrolyzer 130 to generate hydrogen and oxygen with the supply of power; and an oxygen storage tank 170, which stores the oxygen generated by electrolysis.

[0084] Among them, Figure 2 As shown, the hydrogen mixed gas generation system of one embodiment of the present invention may include a water supply device 51, which is connected to the hydrogen generation module 100 to supply pure water to the hydrogen generation module 100, and may also include an oxygen exhaust device 53, which is connected to the hydrogen generation module 100 to exhaust the oxygen generated by electrolysis in the hydrogen generation module 100 to the outside.

[0085] Then, the hydrogen storage tank 200 is connected to the hydrogen generation module 100 to receive the hydrogen generated from the hydrogen generation module 100 and store the received hydrogen.

[0086] As an example, Figure 3 As shown, the hydrogen storage tank 200 may include: a tank body 210; a hydrogen flow inlet 230, which is arranged on one side of the tank body 210 and connected to the hydrogen generation module 100 to allow the hydrogen generated in the hydrogen generation module 100 to flow into the interior of the tank body 210; a hydrogen flow path 250, which is connected to the hydrogen flow inlet 230 and allows the hydrogen to flow inside, and separates the water contained in the hydrogen during the flow of the hydrogen; a drain port 270, which is connected to the hydrogen flow path 250 to discharge the water separated from the hydrogen to the outside; and a hydrogen supply port 290, which is arranged on the other side of the tank body 210 and connected to the hydrogen flow path 250 to discharge the hydrogen from which the water has been separated.

[0087] Among them, the hydrogen flow path 250 may include: a first flow path 251, which is arranged at the upper part of the storage tank body 210, and its two ends are respectively connected to the hydrogen flow inlet 230 and the hydrogen supply port 290; and a second flow path 252, which branches from the first flow path 251 and is arranged in a form extending toward the lower part of the storage tank body 210, so as to separate the water contained in the hydrogen flowing through the first flow path 251 from the hydrogen and at the same time make the separated water flow toward the lower part of the hydrogen storage tank 200.

[0088] On the other hand, the drain port 270 may be connected to the second flow path 252 to discharge the water phase separated from the hydrogen and flowing in the second flow path 252 to the outside.

[0089] As described above, the hydrogen storage tank 200 can not only store the hydrogen generated in the hydrogen generation module 100 , but also separate and discharge water contained in the hydrogen generated in the hydrogen generation module 100 .

[0090] On the other hand, Figure 2 As shown, the hydrogen supply port 290 may be connected to a gas mixing unit 700 described later via a hydrogen supply line 11 , and accordingly, the hydrogen from which water is removed and discharged from the hydrogen tank 200 may be supplied to the gas mixing unit 700 via the hydrogen supply line 11 .

[0091] Then, the hydrogen flow regulator 300 is connected to the aforementioned hydrogen tank 200 to regulate the flow of hydrogen discharged from the hydrogen tank 200 .

[0092] As an example, Figure 2 As shown, the hydrogen flow regulating unit 300 may include a hydrogen flow regulating valve 310 , a hydrogen flow measuring instrument 330 , and a hydrogen pressure regulating valve 350 .

[0093] The hydrogen flow rate regulating valve 310 regulates the flow rate of hydrogen discharged from the hydrogen tank 200 and supplied to the gas mixing unit 700 described later. The hydrogen flow rate regulating valve 310 may be in the form of a known flow rate regulating valve provided to regulate the flow rate of a fluid.

[0094] In this case, the hydrogen flow rate regulating valve 310 is provided on the hydrogen supply line 11 connecting the hydrogen tank 200 and the gas mixing unit 700 , so as to regulate the flow rate of hydrogen supplied to the gas mixing unit 700 through the hydrogen supply line 11 .

[0095] On the other hand, the hydrogen flow regulating valve 310 is configured as a solenoid valve, and its operation can be controlled by a control module 600 described later.

[0096] Next, the hydrogen flow meter 330 measures the flow rate of hydrogen supplied to the gas mixing unit 700 . The hydrogen flow meter 330 may be in the form of a known flow sensor or flow meter that is provided in a manner to measure the flow rate of a fluid.

[0097] In this case, the hydrogen flow meter 330 can be configured on the hydrogen supply line 11 connecting the hydrogen storage tank 200 and the gas mixing section 700 to measure the flow of hydrogen supplied to the gas mixing section 700 through the hydrogen supply line 11, and the hydrogen flow meter 330 transmits the measured hydrogen flow value to the control module 600.

[0098] Next, in order to adjust the pressure inside the hydrogen tank 200 , the hydrogen pressure regulating valve 350 adjusts the flow rate of hydrogen discharged from the hydrogen tank 200 to the outside. The hydrogen pressure regulating valve 350 may be in the form of a known proportional control valve.

[0099] In this case, the hydrogen pressure regulating valve 350 is formed in the form of a branch from the hydrogen supply line 11, and is arranged on the hydrogen discharge line 12 for discharging a part of the hydrogen discharged from the hydrogen storage tank 200 to the outside. The flow rate of hydrogen discharged to the outside through the hydrogen discharge line 12 can be adjusted, and the pressure inside the hydrogen storage tank 200 can be adjusted by adjusting the discharge hydrogen flow rate by the hydrogen pressure regulating valve 350.

[0100] On the other hand, the hydrogen pressure regulating valve 350 is provided in the form of a solenoid valve, and its operation can be controlled by the control module 600 .

[0101] Then, the air storage tank 400 receives air supplied from the outside and stores the received air.

[0102] More specifically, the air storage tank 400 may include: a body housing 410, allowing air to flow inside; and a plurality of baffle members 420, which are disposed inside the body housing 410 and relieve or even remove the pulsation of the air flowing into the body housing 410. Accordingly, the air storage tank 400 not only performs the function of storing air, but also simultaneously performs the function of stabilizing the flow of air by relieving or even removing the pulsation of the air flowing into the inside.

[0103] Below, refer to Figures 5 to 12 The structures of the air tank 400 of the hydrogen mixed gas generating system according to one embodiment of the present invention will be described in detail.

[0104] First, if Figure 5 and Figure 6 As shown, as an example, the main body shell 410 can be a cylindrical box shape, and an air inlet 412 for air inflow can be provided on one side in the length direction, and an air supply port 413 for exhausting air passing through multiple partition parts 420 described later can be provided on the other side in the length direction.

[0105] In this case, if Figure 4 As shown, the hydrogen mixed gas generating system of one embodiment of the present invention may be provided with an air supply pump 71, which is connected to the air inlet 412 of the air storage tank 400 to supply air to the air storage tank 400, and may also include an air filter unit 73, including a high-efficiency air filter (HEPA), a carbon filter, etc. to purify the air supplied to the air storage tank 400.

[0106] On the other hand, Figure 4 As shown, the air supply port 413 may be connected to a gas mixing unit 700 described later via an air supply line 21 , and accordingly, the air exhausted from the air tank 400 may be supplied to the gas mixing unit 700 via the air supply line 21 .

[0107] Next, an air flow space 411 may be formed inside the main body housing 410 , and communicated with the air inlet 412 and the air supply port 413 to allow air to flow.

[0108] In addition, an air outlet 414 may be provided on the other side of the main body housing 410 in the longitudinal direction, communicating with the air flow space 411 , so that a part of the air in the air flow space 411 passing through the plurality of partition members 420 is discharged to the outside.

[0109] In this case, if Figure 4 As shown, the air exhaust port 414 is connected to the air exhaust line 22 , and a portion of the air in the air storage tank 400 can be exhausted to the outside through the air exhaust line 22 .

[0110] On the other hand, as an embodiment, Figure 7 As shown, the main body shell 410 of the air storage tank 400 can be constructed in the form of a first shell 415 and a second shell 416 combined.

[0111] like Figure 8 As shown, as an example, the first shell 415 can be formed with a semi-cylindrical part to constitute the upper part of the main shell 410. In this case, the air inlet 412 and the air supply port 413 can be formed on both sides of the length direction of the first shell 415 respectively.

[0112] As an example, the air inlet 412 can be set to be a hollow hole protruding from one side of the first shell 415 in the longitudinal direction and forming a connection with the internal space of the first shell 415 along the longitudinal direction. The air supply port 413 can be set to be a hollow hole protruding from the other side of the first shell 415 in the longitudinal direction and forming a connection with the internal space of the first shell 415 along the longitudinal direction.

[0113] The air supply port 413 is formed at the upper portion of the other side in the longitudinal direction of the first housing 415 , so that the air passing through the plurality of partition members 420 described later in the air flow space 411 is discharged toward the upper side of the main housing 410 .

[0114] On the other hand, the first housing 415 may be provided with an air outlet 414 at the other side in the longitudinal direction so that a part of the air in the air flow space 411 is discharged to the outside.

[0115] The air outlet 414 is independent of the aforementioned air supply port 413 and may be configured to protrude from the other side of the first housing 415 in the longitudinal direction and to form a hollow hole inside that communicates with the inner space of the first housing 415 along the longitudinal direction.

[0116] On the other hand, the first housing 415 may be provided with a plurality of first partition plate fixing portions 415 - 1 formed in such a manner as to respectively place a plurality of partition plate members 420 described later.

[0117] More specifically, if Figure 8 As shown, as an example, a plurality of first partition fixing portions 415-1 are respectively arranged to form a pair of protrusions in a protruding shape along the circumferential direction of the inner surface of the first shell 415 (when the first shell 415 has a semi-cylindrical shape), and the upper part of the partition member 420 can be inserted between the pair of protrusions.

[0118] Multiple first partition fixing portions 415-1 can be arranged in a manner of being spaced apart from each other at specified intervals along the length direction of the first shell 415. In this case, the multiple first partition fixing portions 415-1 are configured in a manner of being spaced apart from each other at increasingly larger intervals from the air inlet 412 side of the first shell 415 to the air supply port 413 side of the other side.

[0119] Next, the first housing 415 may form a first placement portion 415 - 2 where a sealing member 417 described later is placed.

[0120] More specifically, if Figure 8 As shown, as an example, the first placement portion 415 - 2 may be formed into a groove with a predetermined depth along the lower edge of the first housing 415 toward the upper side of the first housing 415 to insert the upper portion of the ring-shaped sealing member 417 .

[0121] Then, if Figure 8 As shown, the first shell 415 can be provided with a first fastening portion 415-3, which is formed at the lower edge of the first shell 415 to protrude in the lateral direction, and a fastening hole is formed inside along the height direction to insert fastening components such as bolt components, nut components, and pin components. A plurality of first fastening portions 415-3 can be provided along the lower edge of the first shell 415 at specified intervals.

[0122] Then, if Fig. 9 As shown, as an example, the second housing 416 is formed into a semi-cylindrical member and can be provided in a manner that is combined with the lower portion of the first housing 415 to constitute the lower portion of the main housing 410 .

[0123] The second housing 416 may be formed in a manner having a length and a width corresponding to those of the first housing 415 . In this case, the second housing 416 may form a plurality of second partition fixing portions 416 - 1 for respectively placing a plurality of partition members 420 described later.

[0124] More specifically, as an example, Fig. 9 As shown, multiple second partition fixing parts 416-1 are respectively arranged to form a pair of protrusions in a protruding shape along the circumferential direction of the inner surface of the second shell 416 (when the second shell 416 has a semi-cylindrical shape), and the lower part of the partition part 420 can be inserted between the pair of protrusions.

[0125] Multiple second partition fixing parts 416-1 can be arranged in a manner of being spaced apart from each other at a predetermined interval along the length direction of the second shell 416. In this case, the multiple second partition fixing parts 416-1 are configured in a manner of being spaced apart from each other at increasingly larger intervals from one side of the second shell 416 to the other side.

[0126] Among them, the second partition fixing part 416-1 is arranged in the second shell 416 in the manner as described above, and can be set at a position corresponding to the first partition fixing part 415-1 set in the first shell 415 and a number corresponding to the first partition fixing part 415-1. Accordingly, the partition part 420 can be firmly placed in the first partition fixing part 415-1 and the second partition fixing part 416-1 while the first shell 415 and the second shell 416 are combined with each other.

[0127] Next, the second housing 416 may form a second placement portion 416 - 2 for placing a sealing member 417 to be described later.

[0128] More specifically, as an example, Fig. 9 As shown, the second placement portion 416 - 2 may be formed into a groove with a predetermined depth along the upper edge of the second housing 416 toward the lower side of the second housing 416 to insert the lower portion of the ring-shaped sealing member 417 .

[0129] On the other hand, Fig. 9As shown, the second shell 416 can be provided with a second fastening portion 416-3, which is formed on the upper edge of the second shell 416 to protrude in the lateral direction, and a fastening hole is formed inside along the height direction to insert fastening components such as bolt components, nut components, and pin components. A plurality of second fastening portions 416-3 can be provided along the lower edge of the second shell 416 at specified intervals.

[0130] Among them, the second fastening parts 416-3 can be set in a number corresponding to the first fastening parts 415-3 set in the first shell 415 at the position corresponding to the first fastening parts 415-3 set. Accordingly, the first shell 415 and the second shell 416 can be firmly combined into one by fastening bolt parts, nut parts, pin parts, etc. in the fastening holes of the first fastening parts 415-3 and the second fastening parts 416-3 when the edge of the lower part of the first shell 415 is connected to the edge of the upper part of the second shell 416.

[0131] In this case, if Figure 7 and Fig.11 As shown, as an example, a ring-shaped sealing component 417 formed of rubber material can be arranged between a first placement portion 415-2 formed by the lower edge of the first shell 415 and a second placement portion 416-2 formed by the upper edge of the second shell 416 that are connected to each other.

[0132] Then, if Figure 6 As shown, multiple partition components 420 respectively form flow holes 420h for air to pass through, and are arranged at specified intervals in the air flow space 411 of the main body shell 410 along the length direction of the main body shell 410, so as to stabilize the flow of air by alleviating or even eliminating the pulsation of the air flowing into the main body shell 410.

[0133] Among them, the air storage tank 400 of one embodiment of the present invention is characterized in that Fig.10 As shown, the plurality of partition members 420 are composed of a porous partition member 421 provided with a plurality of flow holes 421h and a single-hole partition member 422 disposed adjacent to the porous partition member 421 and having a single flow hole 422h.

[0134] More specifically, the plurality of partition members 420 is characterized in that they are composed of a plurality of porous partition members 421 and a plurality of single-hole partition members 422 , and the plurality of porous partition members 421 and the plurality of single-hole partition members 422 are alternately arranged along the length direction of the main body shell 410 .

[0135] Among them, Fig.12 As shown, as an example, the porous partition member 421 can be provided as a disk-shaped member having a predetermined diameter, and a plurality of flow holes 421h for allowing air to pass therethrough can be formed in the porous partition member 421 .

[0136] The multiple flow holes 421h set in the porous partition part 421 can be formed in a form that penetrates the porous partition part 421 in the thickness direction. In this case, the multiple flow holes 421h can be arranged at specified intervals in the circumferential direction on a circle separated from the center of the porous partition part 421 by specified intervals.

[0137] The porous partition component 421 can be arranged in the air flow space 411 of the main body shell 410 in the form of the first partition fixing part 415-1 of the first shell 415 and the second partition fixing part 416-1 of the second shell 416 with the upper part and the lower part respectively placed on the first partition fixing part 415-1 of the second shell 416. The porous partition component 421 can be arranged in the air flow space 411 of the main body shell 410 so that the air flowing into the air flow space 411 of the main body shell 410 passes through multiple circulation holes 421h to reduce the pressure of the flowing air.

[0138] Then, if Fig.12 As shown, as an example, similar to the porous partition member 421, the single-hole partition member 422 can be set as a disk-shaped member with a predetermined diameter, and a single flow hole 422h for air to pass through can be formed in the single-hole partition member 422.

[0139] One flow hole 422 h of the single-hole partition member 422 may be formed to penetrate the single-hole partition member 422 in the thickness direction. In this case, the one flow hole 422 h may be arranged in the center of the single-hole partition member 422 .

[0140] The single-hole partition component 422 can be arranged in the air flow space 411 of the main body shell 410 in the form of the upper side portion and the lower side portion being placed on the first partition fixing portion 415-1 of the aforementioned first shell 415 and the second partition fixing portion 416-1 of the second shell 416 respectively. In this case, the single-hole partition component 422 is arranged adjacent to the aforementioned porous partition component 421, and is arranged on the downstream side relative to the air flow direction of the porous partition component 421, so that the air discharged from the multiple flow holes 421h of the porous partition component 421 is mixed and arranged through the flow holes 422h arranged in the center part to pass through the porous partition component 421. Air.

[0141] Among them, the single-hole partition member 422 may be formed to have a size larger than the size of each of the plurality of flow holes 421 h included in the multi-hole partition member 421 .

[0142] On the other hand, as mentioned above, a plurality of porous partition components 421 and single-hole partition components 422 can be alternately arranged along the length direction of the main body shell 410, accordingly, the porous partition component 421 can be arranged on the downstream side of the air flow direction of the single-hole partition component 422, and the air that passes through the flow hole 422h arranged in the center of the single-hole partition component 422 and increases the flow rate will flow into the multiple flow holes 421h of other porous partition components 421 after colliding with the central part of the porous partition component 421 and losing part of the kinetic energy.

[0143] In this way, the air storage tank 400 of an embodiment of the present invention has multiple porous partition components 421 and multiple single-hole partition components 422 alternately arranged in multiple layers along the length direction of the main body shell 410 inside the main body shell 410, so that the air flowing into the interior of the main body shell 410 repeats the process described above, thereby making the air passing through the multiple porous partition components 421 and the single-hole partition component 422 in a state where the pulsation is alleviated or even cleared.

[0144] On the other hand, the air storage tank 400 of one embodiment of the present invention can adjust the number of porous partition components 421 and single-hole partition components 422 provided inside the main body shell 410 according to the capacity of the air supply pump 71 connected to the air storage tank 400. In this case, in order to produce a greater decompression effect in the air flowing into the main body shell 410, a porous partition component 421 can be arranged on the side of the air inlet 412 of the main body shell 410.

[0145] Furthermore, in order to form a laminar flow on the air supply port 413 and the air discharge port 414 side of the main body casing 410 , a porous partition member 421 may be disposed on the air supply port 413 and the air discharge port 414 side of the main body casing 410 .

[0146] Then, if Fig.11 As shown, the air storage tank 400 of one embodiment of the present invention can configure multiple partition components 420 composed of a porous partition component 421 and a single-hole partition component 422 with the spacing d between them becoming larger and larger from the air inlet 412 side of the main body shell 410 to the air supply port 413 side.

[0147] Among them, the multiple partition parts 420 are configured with the spacing d between them becoming larger and larger, including the multiple partition parts 420 being configured with the spacing d between them continuously becoming larger and the multiple partition parts 420 being configured with the spacing d between them becoming larger according to different intervals in the main body shell 410 (the partition parts 420 configured in a specific interval are configured with the same spacing d between them, but the partition parts 420 in different intervals are configured with different spacing d).

[0148] On the other hand, the structure of the partition part 420 having the flow hole 420h forms turbulence in the area after the air flowing into the air flow space 411 of the main body shell 410 passes through the flow hole 420h of the partition part 420, and then the air moves in the air flow space 411 and gradually forms a stable flow.

[0149] Among them, as mentioned above, the air storage tank 400 of an embodiment of the present application can be connected to an air supply pump 71 that supplies air or other fluids on the air inlet 412 side, and the air supply port 413 side can be connected to the gas mixing unit 700 described later through the air supply line 21 to supply air to the gas mixing unit 700.

[0150] Accordingly, at the front end of the main body shell 410 which is the area where air flows in from the air supply pump 71, the spacing d between the multiple partition members 420 is made small to actively induce turbulence of the inflowing air and alleviate the pulsation of the air, and at the rear end of the main body shell 410 which supplies air to the gas mixing section 700, the spacing d between the multiple partition members 420 is made large to stabilize the flow state of the air to uniformly form the flow rate of the air supplied to the gas mixing section 700.

[0151] On the other hand, Fig.11 As shown, the air storage tank 400 of one embodiment of the present invention can make the size of the flow hole 421h of the porous partition component 421 larger and larger from the air inlet 412 side of the main body shell 410 to the air supply port 413 side, and can make the size of the flow hole 422h of the single-hole partition component 422 larger and larger from the air inlet 412 side of the main body shell 410 to the air supply port 413 side.

[0152] Among them, making the size of the flow hole 421h of the porous partition part 421 and the size of the flow hole 422h of the single-hole partition part 422 larger and larger includes making the size of the flow hole 421h of the porous partition part 421 and the size of the flow hole 422h of the single-hole partition part 422 continuously increase respectively and making the size of the flow hole 421h of the porous partition part 421 and the size of the flow hole 422h of the single-hole partition part 422 larger and larger in different intervals in the main body shell 410 (the size of the flow hole 421h of the porous partition part 421 arranged in a specific interval is the same, and the size of the flow hole 421h of the porous partition part 421 in different intervals is different, and the size of the flow hole 422h of the single-hole partition part 422 arranged in a specific interval is the same, and the size of the flow hole 422h of the single-hole partition part 422 in different intervals is different).

[0153] On the other hand, as described above, the structure of the partition member 420 having the flow hole 420h is such that when the air flowing into the air flow space 411 of the main body shell 410 passes through the flow hole 420h of the partition member 420, turbulence is formed in the area after passing through the flow hole 420h, and then the air moves in the air flow space 411 and gradually forms a stable flow. In this case, the smaller the size of the flow hole 420h of the partition member 420, the larger the instantaneous pressure fluctuation amplitude of the air, and the longer the moving distance required for the air to form a stable flow.

[0154] Accordingly, at the rear end of the main body shell 410 that supplies air to the gas mixing section 700, the flow hole 420h of the partition member 420 is made larger to reduce the amplitude of the instantaneous pressure fluctuation of the air, thereby fully realizing a stable air flow state within the preset separation interval d of the multiple partition members 420.

[0155] Furthermore, as mentioned above, a porous partition member 421 can be arranged on the air supply port 413 and the air exhaust port 414 side of the main body shell 410 to form laminar flow on the air supply port 413 and the air exhaust port 414 side of the main body shell 410. In this case, the multiple flow holes 421h of the porous partition member 421 respectively supply air in a uniform state, which will be conducive to the formation of laminar flow. Therefore, the size of the flow hole 422h of the single-hole partition member 422 arranged on the air exhaust port 414 and the air supply port 413 side of the main body shell 410 can be made larger than the size of the flow hole 422h of the single-hole partition member 422 arranged on the air inlet 412 side of the main body shell 410.

[0156] As described above, the air storage tank 400 of the hydrogen mixed gas generating system according to one embodiment of the present invention not only serves to store the air flowing in from the outside, but also serves to stabilize the air flow by alleviating or even removing the pulsation of the air flowing in. Therefore, the hydrogen mixed gas generating system according to one embodiment of the present invention can supply air to the gas mixing section 700 more stably by providing the air storage tank 400.

[0157] Then, the air flow adjustment unit 500 is connected to the aforementioned air tank 400 to adjust the flow of the air exhausted from the air tank 400 .

[0158] As an example, Figure 4 As shown, the air flow regulating unit 500 may include an air flow regulating valve 510 , an air flow measuring instrument 530 , and an air pressure regulating valve 550 .

[0159] The air flow regulating valve 510 regulates the flow rate of air discharged from the air tank 400 and supplied to the gas mixing unit 700 described later. The air flow regulating valve 510 may be in the form of a known flow regulating valve that is provided in a manner to regulate the flow rate of a fluid.

[0160] In this case, the air flow regulating valve 510 is disposed on the air supply line 21 connecting the air tank 400 and the gas mixing unit 700 , and can regulate the flow rate of air supplied to the gas mixing unit 700 through the air supply line 21 .

[0161] On the other hand, the air flow regulating valve 510 is provided in the form of a solenoid valve, and its operation can be controlled by the control module 600 .

[0162] Next, the air flow meter 530 measures the flow rate of the air supplied to the gas mixing unit 700 . The air flow meter 530 may be in the form of a known flow sensor or flow meter that is provided in a manner to measure the flow rate of a fluid.

[0163] In this case, the air flow meter 530 can be configured on the air supply line 21 connecting the air storage tank 400 and the gas mixing section 700 to measure the flow of air supplied to the gas mixing section 700 through the air supply line 21, and the air flow meter 530 can transmit the measured air flow value to the control module 600.

[0164] Next, in order to adjust the pressure inside the air storage tank 400 , the air pressure regulating valve 550 adjusts the flow rate of the air discharged from the air storage tank 400 to the outside. The air pressure regulating valve 550 may be in the form of a known proportional control valve.

[0165] In this case, the air pressure regulating valve 550 can be configured on the air exhaust line 22 connected to the air exhaust port 414 of the air storage tank 400 to discharge part of the air in the air storage tank 400 to the outside, and adjust the flow rate of air discharged to the outside through the air exhaust line 22. The pressure inside the air storage tank 400 can be adjusted by adjusting the exhaust air flow rate through the air pressure regulating valve 550.

[0166] On the other hand, the air pressure regulating valve 550 is provided in the form of a solenoid valve, and its operation can be controlled by the control module 600 .

[0167] Then, the control module 600 is configured to control the operation of the hydrogen flow regulating unit 300 and the air flow regulating unit 500 .

[0168] Among them, the control module 600 can be set to a computer device including a central processing unit (central processing unit (CPU), etc.), a memory (random access memory (RAM), read-only memory (ROM), etc.), a storage device (hard disk, solid-state drive (SSD), etc.), and a communication device. As one embodiment, the control module 600 can be set to a micro control unit (MCU, Micro Controller Unit).

[0169] The control module 600 can be electrically connected to the hydrogen flow regulating valve 310 , the hydrogen flow measuring instrument 330 and the hydrogen pressure regulating valve 350 of the hydrogen flow regulating unit 300 , and can also be electrically connected to the air flow regulating valve 510 , the air flow measuring instrument 530 and the air pressure regulating valve 550 of the air flow regulating unit 500 .

[0170] Accordingly, the control module 600 can receive hydrogen flow values ​​and air flow values ​​from the hydrogen flow meter 330 and the air flow meter 530 respectively, and can control the operation of the hydrogen flow regulating valve 310, the hydrogen pressure regulating valve 350, the air flow regulating valve 510 and the air pressure regulating valve 550.

[0171] On the other hand, the control module 600 may control the operation of the hydrogen flow regulator 300 to supply hydrogen at a predetermined flow rate to the gas mixer 700 described later.

[0172] More specifically, the control module 600 may control the operation of the hydrogen pressure regulating valve 350 according to the hydrogen flow value measured by the hydrogen flow meter 330 of the hydrogen flow regulating unit 300 .

[0173] As one embodiment, when the hydrogen flow value measured by the hydrogen flow meter 330 exceeds the normal range and becomes larger, the control module 600 controls the operation of the hydrogen pressure regulating valve 350 to open the hydrogen pressure regulating valve 350. When the hydrogen pressure regulating valve 350 is opened, the internal pressure of the hydrogen storage tank 200 is reduced, thereby adjusting the flow rate of hydrogen discharged from the hydrogen storage tank 200 and the flow rate of hydrogen supplied to the gas mixing section 700 to become smaller.

[0174] On the contrary, when the hydrogen flow value measured by the hydrogen flow meter 330 exceeds the normal range and becomes smaller, the control module 600 can control the operation of the hydrogen pressure regulating valve 350 to close the hydrogen pressure regulating valve 350. When the hydrogen pressure regulating valve 350 is closed, the internal pressure of the hydrogen storage tank 200 increases, thereby adjusting the flow rate of hydrogen discharged from the hydrogen storage tank 200 and the flow rate of hydrogen supplied to the gas mixing section 700 to increase.

[0175] On the other hand, the control module 600 can also control the operation of the hydrogen flow regulating valve 310 of the hydrogen flow regulating unit 300 .

[0176] Next, the control module 600 may supply air to the gas mixing unit 700 at a predetermined flow rate by controlling the operation of the air flow adjustment unit 500 .

[0177] In more detail, the control module 600 may control the operation of the air pressure regulating valve 550 according to the air flow value measured by the air flow measuring instrument 530 of the air flow regulating unit 500 .

[0178] As one embodiment, when the air flow value measured by the air flow meter 530 exceeds the normal range and becomes larger, the control module 600 can control the operation of the air pressure regulating valve 550 to open the air pressure regulating valve 550. When the air pressure regulating valve 550 is opened, the internal pressure of the air storage tank 400 is reduced, thereby adjusting the flow rate of air discharged from the air storage tank 400 and the flow rate of air supplied to the gas mixing section 700 to become smaller.

[0179] On the contrary, when the air flow value measured by the air flow meter 530 exceeds the normal range and becomes smaller, the control module 600 can control the operation of the air pressure regulating valve 550 to close the air pressure regulating valve 550. When the air pressure regulating valve 550 is closed, the pressure of the air storage tank 400 increases, thereby adjusting the flow rate of air discharged from the air storage tank 400 and the flow rate of air supplied to the gas mixing section 700 to increase.

[0180] On the other hand, the control module 600 can also control the operation of the air flow regulating valve 510 of the air flow regulating unit 500 .

[0181] Next, when the hydrogen flow value measured by the hydrogen flow meter 330 and the air flow value measured by the air flow meter 530 are both beyond the normal range, the control module 600 may control the operation of the air pressure regulating valve 550 first and then control the operation of the hydrogen pressure regulating valve 350 .

[0182] For example, when the hydrogen flow value measured by the hydrogen flow meter 330 exceeds the normal range and becomes larger, and the air flow value measured by the air flow meter 530 exceeds the normal range and becomes smaller, the control module 600 first increases the internal pressure of the air storage tank 400 by controlling the closing of the air pressure regulating valve 550, and then reduces the internal pressure of the hydrogen storage tank 200 by controlling the opening of the hydrogen pressure regulating valve 350.

[0183] Since the flow rate of air supplied to the gas mixing unit 700 is much larger than the flow rate of hydrogen gas, the control module 600 is configured to be able to adjust the supply flow rate of air in advance as described above.

[0184] Then, the gas mixing unit 700 is connected to the hydrogen tank 200 to allow the hydrogen discharged from the hydrogen tank 200 to flow in, and is connected to the air tank 400 to allow the air discharged from the air tank 400 to flow in, so that the inflowing hydrogen and air are mixed inside.

[0185] like Figure 1 As shown, the gas mixing unit 700 is connected to the hydrogen tank 200 through the hydrogen supply line 11 to receive hydrogen, and is connected to the air tank 400 through the air supply line 21 to receive air from the air tank 400 .

[0186] The hydrogen gas and the air flowing into the gas mixing unit 700 are uniformly mixed inside the gas mixing unit 700 , thereby generating a hydrogen mixed gas in which the hydrogen gas and the air are mixed inside the gas mixing unit 700 .

[0187] In this case, the flow rates of hydrogen and air flowing into the gas mixing section 700 are maintained at specified flow rates through the hydrogen flow regulating section 300, the air flow regulating section 500 and the control module 600, so that the mixing ratio of hydrogen and air in the hydrogen mixed gas generated inside the gas mixing section 700 can be maintained at a specified ratio.

[0188] On the other hand, as one embodiment, the gas mixing unit 700 may be provided in the form of a pipe member having a predetermined diameter.

[0189] Then, the hydrogen mixed gas generating system according to an embodiment of the present invention may further include a mixed gas sterilization unit 800 connected to the gas mixing unit 700 to receive a hydrogen mixed gas of hydrogen and air from the gas mixing unit 700 and sterilize the received hydrogen mixed gas.

[0190] As one embodiment, the mixed gas sterilization unit 800 can be configured as a sterilization device including an ultraviolet light emitting diode (UV LED) to sterilize the hydrogen mixed gas supplied from the gas mixing unit 700. In this case, the sterilized hydrogen mixed gas can be supplied to medical devices such as a hydrogen inhaler (not shown).

[0191] As described above, the hydrogen mixed gas generating system according to one embodiment of the present invention can stably generate hydrogen mixed gas for medical use that maintains a predetermined mixing ratio of hydrogen gas to air.

[0192] All the structural elements constituting the embodiments of the present invention are described above in a manner of being combined or working in combination, but the present invention is not limited to the above embodiments. That is, as long as it is within the scope of the object of the present invention, one or more of all the structural elements can be selectively combined to operate.

[0193] The present invention is specifically described below by enumerating embodiments and experimental examples in detail. However, the embodiments of the present invention can be modified into various other forms, and the scope of the present invention should not be interpreted as being limited to the embodiments described in detail below. The embodiments of the present invention are provided only to more fully describe the present invention to those of ordinary skill in the art to which the present invention belongs.

[0194] Experimental Example 1: Clinical Research Subjects

[0195] Participants in the clinical study were recruited through the recruitment announcement of the researchers. This study was approved by the Institutional Review Board (IRB) of Yonsei University Wonju Severance Christian Hospital (approval number: CR323002) and registered with Clinical Trials.gov, which is a clinical registration institution of the National Institutes of Health (NIH) of the United States (registration number: identification number NCT05891938). This clinical study was conducted on middle-aged and elderly people aged 40 to 70 years old. Clinical subjects who met the selection criteria and exclusion criteria signed a consent form after screening, analyzed oxidative stress and inflammatory indicators and dementia-related indicators, and implemented the Mini-Cognitive Function Examination (MMSE-K). In addition, physical examination (height and weight), demographic data (sex and age), medical history / medication history, and vital signs (temperature, blood pressure, and pulse) were recorded at the time of the visit. All processes and results of this study were kept confidential.

[0196] Clinical subjects meet the criteria shown in Table 1 below

[0197] Table 1

[0198]

[0199]

[0200] The demographic characteristics of the above clinical subjects are shown in Table 2 below

[0201] Table 2

[0202]

[0203] The clinical subjects were used as subjects, and a mixed gas containing 2 weight percent hydrogen and 98 weight percent filtered air generated by the hydrogen mixed gas generation system described above was provided through a nasal cannula for 30 minutes every day for 4 weeks, and the following measurements were performed.

[0204] Experimental Example 2: Determination of total reactive oxygen species (ROS) and nitric oxide levels

[0205] Total oxidative stress (ROS) in the blood was assessed by oxidation of 2-4-dichlorodihydrofluoresceindiacetate (DCFH-DA). A total of 50 μL of serum sample was placed in a 96-well microplate. After adding 100 μL of 10 μL of 2-4-dichlorodihydrofluoresceindiacetate (DCFH-DA) to the well, the microplate was reacted for 30 minutes in the dark. Then, a multi-function microplate reader (DTX-880, Beckman Coulter) was used for analysis.

[0206] In addition, the production of nitric oxide in the blood was measured using Griess reagent (Promega). 50 μL of serum sample was added to each well, and then 50 μL of sulfonamide solution was added to each well and reacted in the dark at room temperature for 10 minutes. Then, 50 μL of N-(1-naphthyl)ethylenediamine (NED) was added to each well and reacted in a dark room at room temperature for 15 minutes. The optical density (OD) was measured at a wavelength of 520 nm using SpectraMax ABS Plus (Molecular devices Ltd.).

[0207] The results of the above-mentioned reactive oxygen species (ROS) and nitric oxide species (NOS) are as follows: Fig.13 shown.

[0208] The above measurement results confirmed that the blood concentrations of ROS (p<0.05) and NO (p<0.01) were significantly reduced after inhalation of hydrogen mixed gas.

[0209] Experimental Example 3: Determination of brain-derived neurotrophic factor levels

[0210] In order to measure brain-derived neurotrophic factor, one of the main markers of dementia and cognitive impairment, in blood, the serum was measured by an enzyme-linked immunosorbent assay (ELISA) method using an antigen-antibody reaction. After placing the serum sample (20 μL) in a 96-well microplate and reacting at room temperature for 2.5 hours, the microplate was washed three times and then 100 μL of biotin-binding substance was added and reacted for 1 hour. After washing three more times, 100 μL of streptavidin-horseradish peroxidase (HRP) solution was added to each well and reacted for 45 minutes. Finally, 3,3',5,5'-tetramethylbenzidine (TMB) substrate was added to each well and reacted at room temperature for 30 minutes, and then the optical density was measured at a wavelength of 450 nm using SpectraMax ABS Plus (Meigu Molecular Instruments).

[0211] The above-mentioned brain-derived neurotrophic factor determination results are as follows Fig.14 shown.

[0212] The above measurement results can confirm that serum brain-derived neurotrophic factor increased significantly after inhalation of hydrogen mixed gas (p < 0.001).

[0213] Experimental Example 4: Determination of β-secretase 1 levels

[0214] In order to measure beta-secretase 1 (beta-site amyloid precursor protein cleaving enzyme 1, BACE-1), serum was used for determination by an enzyme-linked immunosorbent assay method using an antigen-antibody reaction. The serum sample (20 μL) was placed in a 96-well microplate and reacted at room temperature for 2 hours, and then the microplate was washed 3 times. Then, 100 μL of biotin-binding substance was added and reacted for 1 hour and then washed 3 times. Then, 100 μL of streptavidin-horseradish peroxidase solution was added to each well and reacted for 45 minutes. After adding 100 μL of 3,3',5,5'-tetramethylbenzidine (TMB) substrate to each well and reacting at room temperature for 30 minutes, the optical density was measured at a wavelength of 450 nm using SpectraMax ABS Plus (Meigu Molecular Instruments).

[0215] The results of the above-mentioned β-secretase 1 level determination are as follows Fig.15 shown.

[0216] The above measurement results confirmed that the concentration of β-secretase 1 was significantly reduced after inhalation of hydrogen mixed gas (p < 0.01).

[0217] Experimental Example 5: Detection of inflammatory cytokines, amyloid β and Tau protein by multiplex analysis

[0218] In order to examine the blood concentration of inflammatory cytokines such as interleukin-6, monocyte chemoattractant protein-1, beta-amyloid protein, t-Tau, p-Tau and vascular endothelial growth factor A, a Bead Array Suspension Multiplex Kit (Bio-Rad, San Diego, California, USA) was used. Standard serial dilutions were prepared by resuspending in standard diluents at each standard concentration. The bead combination was mixed with a normal serum sample. After washing, the culture plate was cultured at 4°C for 18 hours. After adding the detection antibody, the culture plate was cultured at room temperature for 1 hour. After coating with streptavidin-phycoerythrin solution, it was placed at room temperature for 30 minutes. Then, the culture plate was checked after a washing process (Milipore, Billerica, Massachusetts, USA).

[0219] First, the results of measuring the serum concentrations of amyloid-β and Tau proteins are as follows: Fig.16 shown.

[0220] As mentioned above Fig.16 As shown, it can be confirmed that after inhalation of hydrogen mixed gas, the levels of biomarkers such as Aβ-40 (p<0.01), Aβ-42 (p<0.05), t-Tau (p<0.001), and p-Tau (p<0.05) were significantly reduced.

[0221] In addition, the results of measuring the serum concentrations of monocyte chemoattractant protein-1, interleukin-6, and vascular endothelial growth factor A are as follows: Fig.17 shown.

[0222] As mentioned above Fig.17 As shown, it can be confirmed that after inhalation of hydrogen mixed gas, the levels of monocyte chemoattractant protein-1 (p < 0.001), interleukin-6 (p < 0.02), and vascular endothelial growth factor A, which are inflammation-related molecular markers, were significantly reduced.

Claims

1. An inhalation pharmaceutical composition, characterized in that: For preventing, improving or treating cognitive dysfunction, the composition comprises hydrogen.

2. The inhalation pharmaceutical composition according to claim 1, characterized in that The above hydrogen is contained in an amount of 1 to 5 weight percent.

3. The inhalation pharmaceutical composition according to claim 1, characterized in that The above-mentioned cognitive dysfunction is dementia, Parkinson's disease, Binswanger's disease, learning disability, mild cognitive impairment, Pick's disease, agnosia, amnesia, aphasia, apraxia or delirium.

4. The inhalation pharmaceutical composition according to claim 1, characterized in that The composition inhibits the generation of nitric oxide and the accumulation of reactive oxygen species and inflammation caused by oxidative stress in nerve cells.

5. The inhalation pharmaceutical composition according to claim 1, characterized in that: The composition induces the production of one or more nerve growth factors selected from the group consisting of brain-derived neurotrophic factor, fibroblast growth factor 2, insulin-like growth factor 1, octamer-binding transcription factor 4, midbrain astrocyte-derived neurotrophic factor, transforming growth factor β1 and placental growth factor.

6. The inhalation pharmaceutical composition according to claim 1, characterized in that: The composition inhibits the generation of β-amyloid protein and reduces the expression of Tau protein.

7. The inhalation pharmaceutical composition according to claim 1, characterized in that: The above composition is prepared by a system comprising the following parts: A hydrogen generation module that generates hydrogen by electrolyzing water; a hydrogen storage tank connected to the hydrogen generation module, receiving the hydrogen generated from the hydrogen generation module and storing the received hydrogen; A hydrogen flow regulating unit connected to the hydrogen storage tank to regulate the flow of hydrogen discharged from the hydrogen storage tank; an air storage tank, receiving air supplied from the outside and storing the received air; An air flow regulating unit connected to the air storage tank to regulate the flow of air discharged from the air storage tank; A gas mixing unit connected to the hydrogen tank to allow the hydrogen discharged from the hydrogen tank to flow in, and connected to the air tank to allow the air discharged from the air tank to flow in, and mixing the inflowing hydrogen and air inside; as well as The control module controls the operation of the hydrogen flow regulating unit and the air flow regulating unit.

8. The inhalation pharmaceutical composition according to claim 7, characterized in that: The hydrogen tank includes a hydrogen flow path inside thereof through which the hydrogen received from the hydrogen generation module flows. In the process of flowing the hydrogen through the hydrogen flow path, water contained in the hydrogen is separated and the separated water is discharged to the outside.

9. The inhalation pharmaceutical composition according to claim 7, characterized in that: The above-mentioned air tank includes: A body shell, forming an air flow space inside; and A plurality of partition members, each having a flow hole formed so as to allow air to pass therethrough, are arranged at predetermined intervals from one another in the longitudinal direction of the main body casing in the air flow space of the main body casing.

10. The inhalation pharmaceutical composition according to claim 7, characterized in that: The hydrogen flow regulating unit comprises: A hydrogen flow regulating valve for regulating the flow of hydrogen discharged from the hydrogen storage tank and supplied to the gas mixing unit; a hydrogen flow meter for measuring the flow rate of hydrogen supplied to the gas mixing unit; and The hydrogen pressure regulating valve regulates the flow rate of hydrogen discharged from the hydrogen tank to the outside in order to regulate the pressure inside the hydrogen tank.

11. The inhalation pharmaceutical composition according to claim 7, characterized in that: The air flow regulating unit comprises: an air flow regulating valve for regulating the flow of air discharged from the air storage tank and supplied to the gas mixing unit; an air flow measuring instrument for measuring the flow rate of air supplied to the gas mixing unit; and The air pressure regulating valve adjusts the flow rate of air discharged from the air tank to the outside in order to adjust the pressure inside the air tank.

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