Preventive or therapeutic agent for attention deficit hyperactivity disorder

Abstract

[Problem] To provide a medicine, etc., capable of preventing or treating attention-deficit hyperactivity disorder. [Solution] Attention-deficit hyperactivity disorder can be prevented or treated by orally administering silicon fine particles or placing silicon fine particles on the skin or a mucosa. The silicon fine particles are particles that generate hydrogen upon contact with water with pH 7 or higher. Provided are a prophylactic or therapeutic agent for attention-deficit hyperactivity disorder, a pharmaceutical composition, a medical instrument, a food or a beverage, each containing the silicon fine particles. Preferably, the silicon fine particles are silicon microparticles that have a film of silicon oxide carrying a hydroxyl group added thereto and / or aggregates of these silicon microparticles.

Description

[Technical Field]

[0001] The present invention relates to the prevention or treatment of attention deficit hyperactivity disorder. [Background technology]

[0002] Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental or behavioral disorder characterized by three cardinal features: hyperactivity, impulsivity, and inattention. Its prevalence in Japan is estimated to be approximately 3-5% among school-age children and 2-2.5% among adults. Clinically, ADHD is classified into three types based on the individual's characteristics: predominantly inattentive type, predominantly hyperactive-impulsive type, and combined type. There is no cure for ADHD; only symptomatic treatment is available. In drug therapy, the first step involves the prescription of a single central nervous system stimulant (methylphenidate hydrochloride or atomoxetine hydrochloride). If insufficient efficacy is observed even after administration of the maximum recommended optimal dose of each drug or if serious side effects occur during dose increase, the patient moves on to the second step, in which the other central nervous system stimulant not selected in the first step is selected. If efficacy is still insufficient, the patient moves on to the third step, in which the decision to discontinue drug therapy is considered. If drug therapy is continued, the patient will move to the fourth stage, which involves a drug therapy chosen from three options: a combination of two central nervous system stimulants, a combination of one central nervous system stimulant and a mood regulator, or a combination of one central nervous system stimulant and an antipsychotic. However, caution is required as mood regulators and antipsychotics are prescribed off-label for attention deficit hyperactivity disorder.

[0003] While reactive oxygen species are necessary for life, they are known to oxidize and damage the cells that make up living organisms. Reactive oxygen species include superoxide anion radicals, hydroxyl radicals, hydrogen peroxide, and singlet oxygen. Hydroxyl radicals are highly oxidizing radicals, and when generated in living organisms, they oxidize nearby substances such as DNA, lipids, and proteins, causing damage to organs. This action of hydroxyl radicals is believed to cause various diseases, including cancer and lifestyle-related diseases, as well as aging.

[0004] Hydrogen is known as a substance that can eliminate hydroxyl radicals generated in the body. When hydrogen reacts with hydroxyl radicals, it produces water, which does not produce substances harmful to the body. Therefore, there have been many reports on hydrogen water, which contains hydrogen that can eliminate hydroxyl radicals in the body.

[0005] However, the saturated hydrogen concentration is 1.6 ppm at room temperature, and the amount of hydrogen contained in 1 liter of hydrogen water, even at saturated state, is only 18 ml (milliliters) of gas. Furthermore, hydrogen molecules are small, so hydrogen in hydrogen water passes through the container and diffuses into the air, making it difficult to maintain the amount of dissolved hydrogen in hydrogen water. Even if highly concentrated hydrogen water is ingested, much of the hydrogen in the hydrogen water will gasify in the upper digestive tract, such as the stomach, which can cause aerophagia (commonly known as "burping"). Therefore, ingesting hydrogen water does not easily deliver sufficient hydrogen to the body to react with hydroxyl radicals in the body. Furthermore, even if hydrogen is absorbed and transported to various organs, its concentration returns to its pre-intake concentration within about an hour. Inhaling gaseous hydrogen in daily life is also difficult.

[0006] Silicon microparticles can generate hydrogen when they come into contact with water. This reaction hardly progresses when they come into contact with water with a pH of less than 5, but the reaction progresses when they come into contact with water with a pH of 7 or higher, and the reaction progresses more rapidly at a pH of 8 or higher. Furthermore, the reaction proceeds favorably when the silicon microparticles are surface-treated. Furthermore, while the silicon microparticles are in contact with water, they continue to generate hydrogen for 20 hours or more, and under certain conditions, 1 g of silicon microparticles can generate 400 ml or more of hydrogen (Patent Document 1, Patent Document 2, Non-Patent Document 1). 400 ml of hydrogen is equivalent to the hydrogen contained in 22 liters of saturated hydrogen water.

[0007] Patent Document 3 describes a solid preparation that contains silicon microparticles as a main component and has hydrogen generating ability. However, it does not state that silicon microparticles can prevent or treat diseases.

[0008] Patent Document 4 describes a hydrogen supply material comprising a medium containing silicon microparticles and water. It also describes the use of this hydrogen supply material to supply hydrogen to the skin or mucous membranes. However, it does not describe that silicon microparticles can prevent or treat diseases.

[0009] Patent Document 5 describes the treatment of silicon microparticles with hydrogen peroxide water, but does not describe that silicon microparticles can prevent or treat diseases.

[0010] Patent Document 6 describes a formulation containing silicon microparticles, and cites embodiments in which the silicon microparticles are contained in a "matrix" such as animal medicines, livestock or pet foods, animal feed, plant medicines, plant fertilizers, or plant compost. Although it describes the promotion of animal health and / or disease prevention, it does not state that the silicon microparticles can prevent or treat disease to the extent that they can be used as a medicine.

[0011] Patent Document 7 mainly describes a silicon oxide film formed on the surface of silicon microparticles. It describes possible uses for the silicon microparticles, such as feed, supplements, food additives, and transdermal and / or transmucosal hydrogen uptake, and also describes the promotion of animal health and / or disease prevention. However, it does not describe the ability of silicon microparticles to prevent or treat disease to the extent that they could be used as a pharmaceutical.

[0012] The inventors have found that silicon microparticles can prevent or treat kidney disease, inflammatory diseases (inflammatory bowel disease, arthritis, hepatitis, dermatitis), visceral discomfort, depression or depressive states, Parkinson's disease, autism spectrum disorder, memory disorders, spinal cord injury, hearing loss, cerebral ischemia-reperfusion injury, diabetes, and hangovers, and have filed patent applications (Patent Documents 8 to 11). [Prior art documents] [Patent documents]

[0013] [Patent Document 1] Japanese Patent Application Laid-Open No. 2016-155118 [Patent Document 2] Japanese Patent Application Laid-Open No. 2017-104848 [Patent Document 3] International Publication No. 2017 / 130709 [Patent Document 4] International Publication No. 2018 / 037752 [Patent Document 5] International Publication No. 2018 / 037818 [Patent Document 6] International Publication No. 2018 / 037819 [Patent Document 7] International Publication No. 2019 / 211960 [Patent Document 8] International Publication No. 2019 / 021769 [Patent Document 9] International Publication No. 2019 / 235577 [Patent Document 10] Japanese Patent Application Laid-Open No. 2019-214556 [Patent Document 11] JP 2020-007300 A [Non-patent literature]

[0014] [Non-Patent Document 1] Matsuda, Shinsuke et al., Water decomposition and hydrogen concentration by silicon nanoparticles, Proceedings of the 62nd Spring Meeting of the Japan Society of Applied Physics, 2015, 11a-A27-6 Summary of the Invention [Problem to be solved by the invention]

[0015] An objective of the present invention is to provide a medicine, medical device, food, beverage, or the like for the prevention or treatment of attention deficit hyperactivity disorder. [Means for solving the problem]

[0016] The present inventors have discovered that silicon microparticles can prevent and / or treat attention deficit hyperactivity disorder, and have completed the present invention. 1. A preventive or therapeutic agent for attention deficit hyperactivity disorder containing silicon microparticles. 2. The prophylactic or therapeutic agent according to the preceding item 1, wherein the attention deficit hyperactivity disorder is hyperactivity in attention deficit hyperactivity disorder. 3. The preventive or therapeutic agent according to item 1 or 2 above, wherein the silicon microparticles are silicon-containing microparticles capable of generating hydrogen upon contact with water. 4. The preventive or therapeutic agent according to any one of the preceding items 1 to 3, wherein the silicon-containing microparticles are microparticles containing simple silicon. 5. The preventive or therapeutic agent according to any one of the preceding items 1 to 4, wherein the silicon microparticles are silicon microparticles having a silicon oxide film formed on the surface thereof. 6. The preventive or therapeutic agent according to the preceding item 5, wherein the silicon oxide film is a silicon oxide film having a hydroxyl group added thereto. 7. The preventive or therapeutic agent according to any one of the preceding items 1 to 6, wherein the silicon microparticles are silicon microparticles and / or aggregates of the silicon microparticles. 8. The preventive or therapeutic agent according to the preceding item 7, wherein the silicon microparticles are microparticles made of simple silicon and have a silicon oxide film formed on the surface thereof. 9. The preventive or therapeutic agent according to any one of the preceding items 1 to 6, wherein the silicon microparticles are porous silicon particles. 10. The preventive or therapeutic agent according to any one of items 1 to 9 above, wherein the silicon microparticles are silicon microparticles that have been hydrophilized. 11. The preventive or therapeutic agent according to any one of the preceding items 1 to 10, which is for oral administration. 12. A pharmaceutical composition for preventing or treating attention deficit hyperactivity disorder, comprising the prophylactic or therapeutic agent according to any one of the preceding items 1 to 11. 13. A medical device for preventing or treating attention deficit hyperactivity disorder, comprising the prophylactic or therapeutic agent according to any one of the preceding items 1 to 11. 14. A food or drink for the prevention or treatment of attention deficit hyperactivity disorder, comprising the prophylactic or therapeutic agent according to any one of the preceding items 1 to 11. 15. A therapeutic agent for attention deficit hyperactivity disorder containing silicon microparticles. 16. A method for preventing or treating attention deficit hyperactivity disorder, comprising administering silicon microparticles. 17. A method for treating attention deficit hyperactivity disorder comprising administering silicon microparticles. 18. An agent containing silicon microparticles for use in the prevention or treatment of attention deficit hyperactivity disorder. 19. An agent for use in treating attention deficit hyperactivity disorder, containing silicon microparticles. 20. Use of silicon microparticles for preparing an agent for the prevention or treatment of attention deficit hyperactivity disorder. 21. Use of silicon microparticles for the preparation of a therapeutic agent for attention deficit hyperactivity disorder. [Effects of the Invention]

[0017] The prophylactic or therapeutic agent of the present invention can prevent and / or treat attention deficit hyperactivity disorder.

[0018] Prevention and treatment using the preventive or therapeutic agent of the present invention can be one of the causal therapies for attention deficit hyperactivity disorder, and is highly effective and safe. Since there is no fundamental treatment for attention deficit hyperactivity disorder and only symptomatic treatment has been available, the discovery of a causal treatment will greatly contribute to future medical care and health promotion.

[0019] Furthermore, unlike hydrogen water, the preventive or therapeutic agent of the present invention does not allow hydrogen to diffuse before administration, which contributes to maintaining the quality of pharmaceutical products and contributing to convenience for manufacturers, sellers, and users. [Brief explanation of the drawings]

[0020] [Figure 1] FIG. 1 is a photograph of silicon microparticles (a mixture of silicon crystallites and their aggregates) taken with a scanning electron microscope (SEM) (Example 2). [Figure 2] FIG. 2 is a graph showing the amount of hydrogen (cumulative amount) generated per 1 g of silicon microparticles by contacting the silicon microparticles obtained in Example 2 with water at 36° C. and pH 8.2. [Figure 3]FIG. 3 is a photograph of silicon microparticles (aggregates of silicon crystallites) taken with a scanning electron microscope (SEM) (Example 3). [Figure 4] 4 is a graph showing the results of the antioxidant capacity (BAP test) of plasma from normal SD rats administered silicon microparticles for 8 weeks, where Con represents the control group and Si represents the group administered silicon microparticles. [Figure 5] Figure 5 shows the results of multivariate analysis of sulfur-related compounds in the large intestine, showing that the control group and the silicon microparticle-administered group can be distinguished by 10 sulfur-related compounds. Con indicates the control group, and Si indicates the silicon microparticle-administered group. [Figure 6] Figure 6 is a graph showing the results of a comparative analysis of the amounts of glutathione and glutathione monosulfide in the colons of the silicon microparticle-administered group and the control group (n=6 per group). *p<0.05, t-test [Figure 7] FIG. 7 shows the procedure for producing a mouse model of attention-deficit hyperactivity disorder and the experimental procedure. [Figure 8] Figure 8 is a graph showing the results of the hyperactivity test using an open field. The vertical axis shows the total distance traveled by mice in the open field over a 10-minute period. Compared to the group (n=14) given normal diet and saline (far left), the group (n=31) given normal diet and 6-OHDA showed a significant increase in distance traveled, indicating hyperactivity (center). In contrast, the group (n=19) given normal diet and 6-OHDA showed an improvement in distance traveled to the same level as the group given normal diet and saline, and hyperactivity was improved (far right). ***p<0.001, **p<0.01, t-test [Figure 9]Figure 9 shows immunohistochemical staining images of coronal sections from the forebrain of a mouse model of attention deficit hyperactivity disorder, showing the status of dopaminergic neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Compared with the group administered saline on a normal diet (far left), the group administered 6-OHDA on a normal diet showed significantly reduced tyrosine hydroxylase (TH) staining in the VTA and SNc, indicating damage to dopaminergic neurons (center). In contrast, the group administered 6-OHDA on a silicon microparticle-containing diet showed improved TH staining to the same level as the group administered saline on a normal diet (far right). [Figure 10] Figure 10 shows immunohistochemical staining images of coronal sections from the midbrain of a mouse model of attention deficit hyperactivity disorder, showing the state of dopaminergic neurons in the striatum. Compared to the group administered saline on a normal diet (far left), the group administered 6-OHDA on a normal diet showed a significant decrease in tyrosine hydroxylase (TH) staining in the striatum, indicating damage to dopaminergic neurons (center). In contrast, the group administered 6-OHDA on a silicon microparticle-containing diet showed an improvement in TH staining to the same level as the group administered saline on a normal diet (far right). DETAILED DESCRIPTION OF THE INVENTION

[0021] The silicon microparticles contained in the preventive or therapeutic agent of the present invention are silicon-containing microparticles that can generate hydrogen when in contact with water.

[0022] The above-mentioned "microparticles containing silicon capable of generating hydrogen upon contact with water" (silicon microparticles capable of generating hydrogen) refers to silicon microparticles that, when contacted with water at 36°C and pH 8.2, continuously generate hydrogen, generating 10 ml or more of hydrogen per gram of silicon microparticles in 24 hours. Preferably, the amount is 20 ml or more, 40 ml or more, 80 ml or more, 150 ml or more, 200 ml or more, or 300 ml or more.

[0023] The silicon-containing microparticles are preferably microparticles containing elemental silicon. The elemental silicon is high-purity silicon. In this specification, high-purity silicon refers to silicon having a purity of 99% or more, preferably 99.9% or more, and more preferably 99.99% or more.

[0024] The silicon microparticles contained in the preventive or therapeutic agent of the present invention are preferably silicon microparticles, aggregates of the silicon microparticles, and / or porous silicon particles.

[0025] The active ingredient of the preventive or therapeutic agent of the present invention is preferably at least one type of particle selected from the group consisting of silicon microparticles, aggregates of silicon microparticles, and porous silicon particles. That is, the preferred active ingredient may be silicon microparticles alone, aggregates of silicon microparticles alone, or porous silicon particles alone. The active ingredient may also contain two or more types of silicon microparticles. The preventive or therapeutic agent of the present invention preferably contains silicon microparticles and / or aggregates of silicon microparticles. More preferably, the main ingredient is aggregates of silicon microparticles.

[0026] When elemental silicon is exposed to the atmosphere, its surface is oxidized to form a silicon oxide film. The silicon microparticles of the present invention are preferably microparticles having a silicon oxide film formed on their surfaces. The preferred silicon microparticles of the present invention are at least one type of particle selected from the group consisting of fine particles made of elemental silicon and having a silicon oxide film formed on their surfaces, aggregates of such silicon microparticles, and porous silicon particles made of porous elemental silicon and having a silicon oxide film formed on their surfaces.

[0027] The silicon content in the silicon microparticles is preferably 10% by weight or more, more preferably 20% by weight or more, even more preferably 50% by weight or more, and most preferably 70% by weight or more.

[0028] The silicon oxide film is preferably a silicon oxide film to which hydroxyl groups (—OH groups) have been added. A silicon oxide film to which hydroxyl groups have been added is a silicon oxide film that has been treated to increase the number of hydroxyl groups in the silicon oxide film. For example, hydroxyl groups can be added to the silicon oxide film by hydrophilization treatment. Silicon microparticles having a silicon oxide film to which hydroxyl groups have been added have improved contact efficiency with water on the surface, which promotes the hydrogen generation reaction and allows a large amount of hydrogen to be generated. The hydrophilization treatment method is not particularly limited, and any known hydrophilization treatment method may be used. Examples include hydrogen peroxide treatment and nitric acid treatment. Hydrogen peroxide treatment is preferred. Hydrogen peroxide treatment can remove hydrogen from SiH groups in the silicon oxide film on the particle surface and add hydroxyl groups to the particle surface.

[0029] The silicon fine particles having a silicon oxide film with hydroxyl groups added thereto on the surface thereof preferably have a surface area of ​​5×10 13 / cm 2 More preferably, it has 1×10 14 / cm 2 More preferably, 3×10 14 / cm 2 The particle surfaces include the surfaces of silicon microparticles, the surfaces of porous silicon particles, the surfaces of aggregates of silicon microparticles, and the surfaces of silicon microparticles that form aggregates.

[0030] A specific method for hydrogen peroxide treatment involves immersing silicon microparticles in hydrogen peroxide and stirring them. The hydrogen peroxide concentration is preferably 1 to 30%, more preferably 1.5 to 20%, even more preferably 2 to 15%, 2.5 to 10%, and most preferably 3 to 5%. The immersion and stirring time is preferably 5 to 90 minutes, more preferably 10 to 80 minutes, and even more preferably 20 to 70 minutes. Most preferably 30 to 60 minutes. Treatment with hydrogen peroxide can improve the hydrophilicity of silicon microparticles, but prolonged treatment time can promote the hydrogen generation reaction from the silicon microparticles, affecting the thickness of the oxide film on the silicon microparticles. The temperature of the hydrogen peroxide during hydrogen peroxide treatment is preferably 20 to 60°C, more preferably 25 to 50°C, more preferably 30 to 40°C, and most preferably 35°C.

[0031] There is no limitation on the shape of the silicon particles, and examples thereof include amorphous, polygonal, spherical, elliptical, and cylindrical shapes.

[0032] The silicon microparticles may be crystalline silicon microparticles having crystallinity. Alternatively, they may be amorphous silicon microparticles having no crystallinity. When they have crystallinity, they may be single crystal or polycrystalline. Crystalline silicon microparticles are preferred, and single crystal silicon microparticles are more preferred.

[0033] The amorphous silicon particles may be amorphous silicon particles formed by a plasma CVD method, a laser ablation method, or the like.

[0034] The silicon oxide film formed on the surface of the silicon microparticles in the present invention may be a silicon oxide film formed by natural oxidation upon exposure to the atmosphere, or may be a silicon oxide film formed artificially by a known method such as chemical oxidation using an oxidizing agent such as nitric acid.

[0035] The thickness of the silicon oxide film may be any thickness that stabilizes the particles made of elemental silicon and enables efficient hydrogen generation. For example, the thickness may be 0.3 nm to 5 nm, 0.3 nm to 3 nm, 0.5 nm to 2.5 nm, 0.7 nm to 2 nm, 0.8 nm to 1.8 nm, or 1.0 nm to 1.7 nm. The silicon oxide film may be a film containing oxides such as SiO, SiO, SiO, and SiO, which are formed when silicon on the surface of the particles made of elemental silicon combines with oxygen. SiO, SiO, SiO, and the like promote the hydrogen generation reaction.

[0036] The silicon microparticles may be crystalline silicon microparticles having crystallinity. Alternatively, they may be amorphous silicon microparticles having no crystallinity. When they have crystallinity, they may be single crystal or polycrystalline. Preferred silicon microparticles are crystalline silicon microparticles, and more preferably single crystal silicon microparticles (hereinafter also referred to as silicon crystallites).

[0037] The silicon microparticles may be a mixture of at least two selected from the group consisting of single crystal silicon microparticles, polycrystalline silicon microparticles, and amorphous silicon microparticles.

[0038] The silicon microparticles in the present invention may be silicon microparticles on which a silicon oxide film is formed naturally or artificially after production of the silicon microparticles, and more preferably, silicon microparticles on which a silicon oxide film is formed on the surface of silicon crystallites.

[0039] The silicon microparticles in the present invention may be particles obtained by pulverizing a mass of silicon element (high-purity silicon) or particles obtained by pulverizing particles of silicon element. When silicon element lumps or particles are pulverized to produce silicon microparticles, the surfaces of the silicon microparticles are naturally oxidized to form a silicon oxide film.

[0040] The particle diameter of the silicon fine particles in the present invention (crystallite diameter when the fine particles are silicon crystallites) is preferably 0.5 nm to 100 μm, more preferably 1 nm to 50 μm, more preferably 1.5 nm to 10 μm, more preferably 2 nm to 5 μm, more preferably 2.5 nm to 1 μm, 5 nm to 500 nm, 7.5 nm to 200 nm, or 10 nm to 100 nm. If the particle diameter is 500 nm or less, a suitable hydrogen generation rate and amount can be obtained, and if it is 200 nm or less, an even more suitable hydrogen generation rate and amount can be obtained.

[0041] The agglomerates of silicon microparticles in the present invention are agglomerates of the above-mentioned silicon microparticles. They may be naturally formed or artificially formed. Preferably, they are agglomerates formed by agglomeration of silicon microparticles on which a silicon oxide film is formed. It is believed that naturally formed agglomerates remain agglomerated in the digestive tract. Preferred agglomerates have a structure with internal voids that allow water molecules to penetrate the agglomerates and react with the internal microparticles. Since the hydrogen generation rate of naturally formed agglomerates does not depend on the agglomerate size, the agglomerates have a structure with internal voids that allow water molecules to penetrate the agglomerates and react with the internal microparticles.

[0042] There are no particular limitations on the size of the silicon microparticle aggregates. The particle size of the silicon microparticle aggregates is preferably 10 nm or more and 500 μm or less. More preferably, it is 50 nm or more and 100 μm or less, and even more preferably, it is 100 nm or more and 50 μm or less. The aggregates can be formed so as to maintain the surface area of ​​the microparticles, and can have a surface area sufficient to achieve high hydrogen generation capacity.

[0043] The particle diameter of the silicon fine particles constituting the silicon fine particle aggregate in the present invention is preferably 0.5 nm to 100 μm, more preferably 1 nm to 50 μm, more preferably 1.5 nm to 10 μm, more preferably 2 nm to 5 μm, more preferably 2.5 nm to 1 μm, 5 nm to 500 nm, 7.5 nm to 200 nm, or 10 nm to 100 nm. The silicon fine particles constituting the silicon aggregate may be crystalline silicon fine particles or amorphous silicon fine particles. A preferred aggregate is an aggregate of silicon crystallites with a crystallite diameter of 1 nm to 10 μm. Preferably, the aggregate is an aggregate of silicon crystallites having a silicon oxide film formed on the surface.

[0044] The preventive or therapeutic agent of the present invention preferably contains silicon crystallites with a crystallite diameter of 1 nm to 1 μm, more preferably 1 nm to 100 nm, with a silicon oxide film formed on the surface thereof, and / or aggregates thereof. Preferably, the agent contains, as a main component, aggregates of silicon crystallites with a silicon oxide film formed on the surface thereof.

[0045] The preventive or therapeutic agent of the present invention preferably contains silicon crystallites with a crystallite diameter of 1 nm to 1 μm, more preferably 1 nm to 100 nm, and contains, as a main component, silicon crystallites having a silicon oxide film with hydroxyl groups added to their surface, and / or aggregates thereof. Preferably, the preventive or therapeutic agent of the present invention contains, as a main component, silicon crystallites having a silicon oxide film with hydroxyl groups added to their surface, and / or aggregates thereof.

[0046] The porous silicon particles may be a porous body of silicon particles. Alternatively, they may be a porous body formed by agglomerating and processing fine silicon particles. The porous silicon particles are preferably particles made of porous silicon alone, with a silicon oxide film formed on the surface. More preferably, the silicon oxide film is a silicon oxide film with hydroxyl groups added thereto.

[0047] The porous silicon particles may be crystalline or amorphous. If the porous silicon particles are crystalline, they may be single crystal or polycrystalline.

[0048] There is no limit to the size of the voids present in the porous silicon particles, but it is usually 1 nm to 1 μm, and the porous silicon particles have a sufficient surface area to achieve high hydrogen generation capacity. There is no particular limit to the size of the porous silicon particles, and it is preferably 200 nm to 400 μm.

[0049] Agglomerates of silicon microparticles and porous silicon particles have a large overall particle size and a large surface area, making them suitable for oral administration. Large particles do not pass through the cell membranes and spaces between cells in the digestive tract, particularly the intestinal tract, and the silicon microparticles are not absorbed into the body, making them excellent from the standpoint of safety.

[0050] There are no particular limitations on the particle size distribution of the silicon microparticles contained in the preventive or therapeutic agent of the present invention, or on the particle size distribution or crystallite size distribution of the microparticles consisting of simple silicon. Polydispersion is also possible. A formulation containing silicon microparticles having a specific range of particle size or crystallite size is also possible. Furthermore, there are no particular limitations on the size distribution of aggregates of silicon microparticles.

[0051] The rate of hydrogen generation can be adjusted by the particle size and particle size distribution of the silicon microparticles and / or the film thickness of the silicon oxide film.

[0052] The method for producing silicon microparticles of the present invention is not particularly limited, but can be produced by physically pulverizing silicon-containing particles to a desired particle size. Suitable examples of physical pulverization methods include bead mill pulverization, planetary ball mill pulverization, shock wave pulverization, high-pressure collision pulverization, jet mill pulverization, or a pulverization method combining two or more of these. Known chemical methods can also be used. From the viewpoint of production cost or ease of production management, physical pulverization is a preferred pulverization method. When microparticles consisting of fine particles of simple silicon are exposed to the atmosphere, their surfaces are oxidized to form a silicon oxide film. Alternatively, after pulverization, a silicon oxide film may be artificially formed by a known method, such as chemical oxidation using an oxidizing agent such as hydrogen peroxide or nitric acid.

[0053] When silicon-containing particles are produced by pulverizing them to a desired particle size using a bead mill, the desired particle size or particle size distribution can be obtained by appropriately changing the size and / or type of beads.

[0054] The silicon-containing particles as the starting material are not limited as long as they are high-purity silicon particles. For example, commercially available high-purity silicon particle powders can be used. The silicon-containing particles as the starting material can be single crystal, polycrystalline, or amorphous.

[0055] This application includes an invention relating to a preventive or therapeutic agent for attention deficit hyperactivity disorder containing silicon microparticles, an invention relating to a method for preventing or treating attention deficit hyperactivity disorder comprising administering silicon microparticles, an invention relating to an agent for use in the prevention or treatment of attention deficit hyperactivity disorder containing silicon microparticles, and an invention relating to the use of silicon microparticles for the preparation of a preventive or therapeutic agent for attention deficit hyperactivity disorder, etc. The description and embodiments, etc. of the invention relating to a preventive or therapeutic agent for attention deficit hyperactivity disorder containing silicon microparticles in this specification are the description and embodiments, etc. of all of these inventions.

[0056] The prophylactic or therapeutic agent for attention deficit hyperactivity disorder of the present invention includes an agent for preventing attention deficit hyperactivity disorder, an agent for treating attention deficit hyperactivity disorder, and an agent for both preventing and treating attention deficit hyperactivity disorder.

[0057] The prophylactic or therapeutic agent of the present invention has the effect of preventing the onset of one or more symptoms of attention deficit hyperactivity disorder, ameliorating the symptoms, suppressing the worsening of the symptoms, preventing the recurrence of the symptoms, and achieving early recovery from the symptoms. Symptoms of attention deficit hyperactivity disorder include hyperactivity, impulsivity, and lack of attention.

[0058] The prophylactic or therapeutic agent of the present invention can be an agent for preventing or treating hyperactivity in attention deficit hyperactivity disorder. Symptoms of hyperactivity include high activity, inability to sit still, inability to stop talking, restlessness and inability to control behavior, etc.

[0059] The prophylactic or therapeutic agent of the present invention can be a therapeutic agent for attention deficit hyperactivity disorder, and exhibits effects such as improving one or more symptoms of attention deficit hyperactivity disorder, suppressing the worsening of symptoms, preventing the recurrence of symptoms, and accelerating recovery from symptoms.

[0060] The prophylactic or therapeutic agent of the present invention can be an agent for treating hyperactivity in attention deficit hyperactivity disorder. Symptoms of hyperactivity include high activity, inability to sit still, inability to stop talking, restlessness and inability to control behavior, etc.

[0061] The silicon microparticles of the present invention have the property of continuing to generate hydrogen for a long period of time (20 hours or more) in vitro. The silicon microparticles of the present invention generate hydrogen when they come into contact with water of pH 7 or higher, and generate even more hydrogen at pH 8 or higher. On the other hand, they have the property of generating almost no hydrogen at pH 5 or lower.

[0062] When the silicon microparticles of the present invention are orally administered, due to the above-mentioned properties, it is thought that almost no hydrogen is generated in the stomach, but hydrogen is generated in the intestines. When the silicon microparticles of the present invention were administered to normal mice, hydrogen generation was confirmed in the cecum, a part of the large intestine, and even when normal mice were fed a normal diet under the same conditions, hydrogen was below the detection limit. Since the retention time of food in the intestines is usually 20 hours or more in humans, it is thought that the preventive or therapeutic agent of the present invention, when administered orally, continues to generate hydrogen in the intestines for a long period of time, allowing hydrogen to be distributed throughout the body.

[0063] It is also believed that by leaving silicon microparticles on the skin or mucous membrane for a long period of time, hydrogen can be delivered transdermally or transmucosally into the body for a long period of time.

[0064] In addition, when rats were administered silicon microparticles and their plasma antioxidant capacity was evaluated (BAP test), it was confirmed that the group administered silicon microparticles had significantly higher antioxidant capacity.

[0065] One mechanism by which attention deficit hyperactivity disorder (ADHD) is prevented and / or treated is thought to be the prolonged generation of hydrogen by the silicon microparticles of the present invention, which are then transported to the blood and various organs, where they selectively react with hydroxyl radicals. Furthermore, the increased antioxidant activity in the blood suggests that this is due to antioxidants produced in the blood. Furthermore, studies using animal models of diseases involving oxidative stress have shown significant effects compared to hydrogen water, suggesting that silicon microparticles may have other effects not found in hydrogen water. Comparing the colonic tissues of mice treated with silicon microparticles with those of untreated mice, the colons of mice treated with silicon microparticles contained higher amounts of glutathione monosulfide and cysteine ​​monosulfide, which are involved in antioxidant activity in vivo. This may be a unique effect of silicon microparticles. Other possible mechanisms include proteins containing metal elements such as cobalt capturing nascent hydrogen generated in the intestine by the reaction of silicon microparticles with water, or proteins with increased reducing power as a result of hydrogen atoms donating electrons, being transported to various organs, where they react with hydroxyl radicals and eliminate them.

[0066] The preventive or therapeutic agent of the present invention can be used in combination with other therapeutic agents for attention deficit hyperactivity disorder. As described above, the mechanism of action of the preventive or therapeutic agent of the present invention is different from the mechanism of action of existing therapeutic agents for attention deficit hyperactivity disorder such as methylphenidate hydrochloride and atomoxetine hydrochloride, and therefore, a higher therapeutic effect is expected when used in combination.

[0067] The subjects for prevention or treatment by the prophylactic or therapeutic agent of the present invention are humans and non-human animals. Preferred non-human animals include pets and livestock.

[0068] The silicon microparticles of the present invention may be administered to humans or non-human animals as one or more of them, or, if necessary, may be mixed with an acceptable additive or carrier and formulated into a form well known to those skilled in the art and administered. Examples of such additives or carriers include pH adjusters (e.g., sodium bicarbonate, sodium carbonate, potassium carbonate, citric acid, etc.), excipients (e.g., sugar derivatives such as mannitol and sorbitol; starch derivatives such as corn starch and potato starch; or cellulose derivatives such as crystalline cellulose), lubricants (e.g., metal stearates such as magnesium stearate; or talc), binders (e.g., hydroxypropyl cellulose, hydroxypropylmethylcellulose, or polyvinylpyrrolidone), disintegrants (e.g., cellulose derivatives such as carboxymethylcellulose and carboxymethylcellulose calcium), and preservatives (e.g., parahydroxybenzoates such as methylparaben and propylparaben; or alcohols such as chlorobutanol and benzyl alcohol). These additives and carriers can be blended into the silicon microparticles either alone or in combination of two or more. Preferred additives include pH adjusters capable of adjusting the pH to 8 or higher. Preferred pH adjusters include sodium bicarbonate.

[0069] There are no particular limitations on the route of administration of the prophylactic or therapeutic agent of the present invention, but preferred routes of administration include oral, transdermal, and transmucosal (oral, rectal, vaginal, etc.) administration.

[0070] Examples of formulations for oral administration include tablets, capsules, granules, powders, syrups (dry syrups), oral jellies, etc. Examples of formulations for transdermal or transmucosal administration include patches, ointments, etc.

[0071] Tablets, capsules, granules, powders, and the like can be made into enteric preparations. For example, tablets, granules, and powders can be provided with an enteric coating. As the enteric coating agent, a gastric insoluble enteric coating agent can be used. Capsules can be made enteric by filling enteric capsules with the silicon microparticles of the present invention.

[0072] The prophylactic or therapeutic agent of the present invention can be formulated into the above-mentioned dosage forms and then administered to humans or non-human animals.

[0073] The content of silicon microparticles in the preventive or therapeutic agent of the present invention is not particularly limited, and examples thereof include 0.1 to 100% by weight, 1 to 99% by weight, and 5 to 95%.

[0074] The dosage and frequency of administration of silicon microparticles in the present invention can be varied as appropriate depending on the recipient, their age, weight, sex, purpose (e.g., prevention or treatment), severity of symptoms, dosage form, route of administration, and other conditions. When administered to humans, the preferred dosage of silicon microparticles is, for example, about 0.1 mg to 10 g per day, preferably about 1 mg to 5 g, and more preferably about 1 mg to 2 g. The frequency of administration may be one or more times per day, or once every few days. For example, it may be one to three times, one to two times, or once per day.

[0075] The agent for preventing or treating attention deficit hyperactivity disorder containing the silicon microparticles of the present invention can be used in medicines, quasi-drugs, medical devices, foods, and beverages.

[0076] The present application also relates to an invention of a pharmaceutical composition for preventing or treating attention deficit hyperactivity disorder, which contains silicon microparticles. The present application also relates to an invention of a pharmaceutical composition for preventing or treating attention deficit hyperactivity disorder, which contains an agent for preventing or treating attention deficit hyperactivity disorder, which contains the silicon microparticles. The pharmaceutical composition of the present invention also includes compositions with mild effects, such as those that fall under the category of quasi-drugs. Embodiments of the pharmaceutical composition of the present invention can include embodiments of the invention relating to the above-mentioned agent for preventing or treating attention deficit hyperactivity disorder.

[0077] The present application also relates to an invention of a medical device for preventing or treating attention deficit hyperactivity disorder, which contains the above-mentioned silicon microparticles as a preventive or therapeutic agent for attention deficit hyperactivity disorder. The present application also relates to an invention of a medical device for preventing or treating attention deficit hyperactivity disorder, which contains the above-mentioned silicon microparticles. The medical device of the present invention refers to tools, instruments, etc. intended to be used for the treatment or prevention of diseases in humans or non-human animals. Examples of medical devices include masks. By wearing the mask of the present invention, hydrogen can be supplied directly to the trachea or lungs. Another example is a bandage.

[0078] The present application also relates to an invention of a food or beverage for preventing or treating attention deficit hyperactivity disorder, which contains the above-mentioned silicon microparticles as a preventive or therapeutic agent for attention deficit hyperactivity disorder. The present application also relates to an invention of a food or beverage for preventing or treating attention deficit hyperactivity disorder, which contains the above-mentioned silicon microparticles. Preferred examples of the food or beverage of the present invention include health foods, functional foods, and foods for specified health uses. These health foods, functional foods, and foods for specified health uses are foods or beverages that can prevent the onset of symptoms of attention deficit hyperactivity disorder and / or prevent the recurrence of symptoms. There are no limitations on the form of the food or beverage. Examples include mixtures in which the food or beverage is mixed with existing foods or beverages, and formulated forms. Examples include tablets, capsules, powders, granules, jellies, and the like.

[0079] The present invention will be explained in more detail below by way of examples, but the present invention is not limited to these examples. [Example]

[0080] Example 1 200 g of high-purity silicon powder (manufactured by Kojundo Chemical Laboratory, particle size distribution <φ5 μm (however, silicon particles with a crystal particle diameter of more than 1 μm), purity 99.9%) was dispersed in 4 L (liter) of 99.5 wt% ethanol solution, and φ0.5 μm zirconia beads (volume 750 ml) were added. The mixture was then pulverized (single-stage pulverization) for 4 hours at a rotation speed of 2500 rpm using a bead mill (manufactured by Imex Co., Ltd., horizontal continuous ready mill (model RHM-08)).

[0081] The ethanol solution containing the micronized silicon particles was separated from the beads by a separation slit provided inside the grinding chamber of the bead mill device, and then heated to 30°C to 35°C using a reduced pressure evaporator. Micronized silicon particles (crystallites) were obtained by evaporating the ethanol solution.

[0082] The fine silicon particles (crystallites) obtained by the above method mainly had a crystallite diameter of 1 nm or more and 100 nm or less, and most of the crystallites formed aggregates. Furthermore, the crystallites were covered with a silicon oxide film, and the thickness of the silicon oxide film was approximately 1 nm. Measurement of these silicon crystallites using an X-ray diffractometer (Rigaku Electric Smart Lab) revealed that the volume distribution showed a mode diameter of 6.6 nm, a median diameter of 14.0 nm, and an average crystallite diameter of 20.3 nm. The resulting mixture of silicon crystallites and their aggregates on which a silicon oxide film was formed is one embodiment of the silicon microparticles that are the active ingredient of the present invention.

[0083] <Example 2> The silicon crystallites and their aggregates obtained in Example 1 were mixed with hydrogen peroxide (3 wt%) in a glass container and stirred at 35°C for 30 minutes. The silicon crystallites and their aggregates treated with hydrogen peroxide were subjected to solid-liquid separation using a known centrifugal separator to remove the hydrogen peroxide. The obtained silicon crystallites and their aggregates were then mixed with an ethanol solution (99.5 wt%) and thoroughly stirred. The silicon crystallites and their aggregates mixed with the ethanol solution were subjected to solid-liquid separation using a known centrifugal separator to remove the highly volatile ethanol solution, and then thoroughly dried. The obtained mixture of silicon crystallites and their aggregates treated with hydrogen peroxide and having a silicon oxide film formed thereon is one embodiment of silicon microparticles, which are the active ingredient of the present invention. A scanning electron microscope (SEM) photograph of the obtained silicon microparticles is shown in Figure 1. The hydrogen generation rate of the obtained silicon crystallite aggregates did not depend on the aggregate size.

[0084] The amount of hydrogen generated from the silicon microparticles (silicon crystallites and their aggregates) obtained in Example 2 was measured. 10 mg of silicon microparticles were placed in a 100 ml glass bottle (borosilicate glass approximately 1 mm thick, ASONE Corporation's Labolan screw cap bottle). Water adjusted to pH 8.2 with sodium bicarbonate was placed in the glass bottle, which was then sealed at a temperature of 36°C, and the hydrogen concentration in the liquid in the glass bottle was measured. A portable dissolved hydrogen meter (Toa DKK Corporation, Model DH-35A) was used to measure the hydrogen concentration. The amount of hydrogen generated per 1 g of silicon microparticles is shown in Figure 2.

[0085] Example 3 Using the same method as in Example 2, the silicon microparticles (silicon crystallites and their aggregates) obtained in Example 1 were treated with hydrogen peroxide, mixed with an ethanol solution, and stirred. The silicon microparticles mixed with the ethanol solution were dried using a spray dryer (ADL311S-A, manufactured by Yamato Scientific). The resulting silicon crystallite aggregates are one embodiment of the silicon microparticles that are the active ingredient of the present invention. A scanning electron microscope (SEM) photograph of the obtained silicon microparticles (silicon crystallite aggregates) is shown in Figure 3.

[0086] Example 4 Single-stage pulverization was carried out in the same manner as in Example 1. The φ0.5 μm zirconia beads (volume 750 ml) used in the single-stage pulverization were automatically separated from the solution containing silicon crystallites in the bead mill pulverization chamber. 0.3 μm zirconia beads (volume 750 ml) were added to the resulting solution containing silicon crystallites, and the silicon crystallites were further pulverized (two-stage pulverization) at a rotation speed of 2500 rpm for 4 hours to refine them.

[0087] The beads were separated from the solution containing silicon crystallites as described above, and the resulting ethanol solution containing silicon crystallites was heated to 40°C using a reduced pressure evaporator as in Example 1. The ethanol evaporated, and two-stage crushed silicon crystallites were obtained. The silicon crystallites thus crushed in two stages and having a silicon oxide film formed thereon are also one embodiment of the silicon microparticles that are the active ingredient of the present invention.

[0088] <Example 5> The mixture of silicon crystallites and their aggregates formed with a silicon oxide film treated with hydrogen peroxide obtained in Example 2 was filled into commercially available capsules No. 3 to obtain a capsule preparation. This capsule preparation contains, as its main component, aggregates of silicon crystallites formed with a silicon oxide film treated with hydrogen peroxide, and further contains silicon crystallites formed with a silicon oxide film treated with hydrogen peroxide.

[0089] <Test example> I. Preparation of silicon microparticle-containing food The silicon microparticles (silicon crystallites and their aggregates) produced in Example 2 were mixed into a normal feed (manufactured by Oriental Yeast Co., Ltd., model number AIN93M) to a concentration of 2.5 wt%. An aqueous citric acid solution (pH 4) was then added in an amount of approximately 0.5 wt% based on the total amount of the silicon microparticles and the feed, and the mixture was kneaded using a known kneading device to obtain a silicon microparticle-containing diet.

[0090] II. Pharmacological effects of silicon microparticles

[0091] A.Improvement of antioxidant capacity SD rats (6 weeks old) were obtained. The group administered silicon microparticles was fed the silicon microparticle-containing diet, while the control group was fed regular feed (normal diet) (Oriental Yeast Co., Ltd., model number AIN93M). After 8 weeks of administration, blood was collected and the antioxidant capacity of the plasma was evaluated (BAP test) (FREE Carrio Duo free radical analyzer). The results are shown in Figure 4. It was shown that the group administered silicon microparticles had significantly higher antioxidant capacity.

[0092] B. Analysis of sulfur-related compounds in the large intestine B-1 Sample preparation C57BL / 6J mice (male, 7 weeks old) were obtained from Japan SLC. The silicon microparticle-treated group was fed the silicon microparticle-containing diet described above, while the control group was fed a regular diet (Oriental Yeast Co., Ltd., model number AIN93M) for one week, with five mice in each group. The large intestine of each mouse was removed under deep anesthesia and divided into three sections: the cecum, colon, and rectum. A portion (approximately 2 cm) from each section, from which the intestinal contents were extracted, was collected and weighed. After weighing, the samples were quickly frozen in powdered dry ice to prepare a colon sample for one mouse. A total of 10 frozen colon samples from five mice per group were used for sulfur index analysis (Euglena Co., Ltd.). Samples were prepared in the same manner at a later date, and a total of 10 frozen colon samples from five mice per group were prepared and used for sulfur index analysis (Euglena Co., Ltd.).

[0093] B-2 Pre-analysis The frozen mouse colon samples (five samples) from the same group obtained in the first sample preparation were combined, and a methanol extract containing an internal standard compound was added (1 ml / g (organ)). The samples were then mashed with a pestle. Then, the samples were centrifuged, and 100 μl of the supernatant was used as the sample. Sulfur compound labeling reagents and other reagents were added to 100 μl of the centrifuged sample supernatant (130 μl in total) and suspended. The centrifuged supernatant (87 μl) was dried in a centrifugal evaporator. After resuspension in 60 μl of water, 5 μl of the supernatant was centrifuged and used as the sample for sulfur index analysis. The samples obtained in the second sample preparation were treated in the same way to obtain samples for sulfur index analysis. The samples used for sulfur index analysis included two samples from the silicon microparticle-administered group (two mixed samples from five mice) and two samples from the control group (two mixed samples from five mice).

[0094] B-3 Sulfur Index Analysis (1) The sulfur compounds contained in the prepared samples were analyzed using the sulfur index method on an LC MSMS 8040 (Shimadzu Corporation). Specifically, relative quantification was performed on all 61 sulfur-related compounds listed in Tables 1 and 2, excluding the internal standard compound (No. 53; camphorsulfonate) and the thiol group modifier (No. 40; monobromobimane). Relative quantification was performed using the peak area of ​​the resulting mass chromatogram (normalized to the internal standard compound). A total of 35 compounds were detected in the colon sample. Based on the detected sulfur-related compound data, a mapping analysis of the similarity between samples (using the R software vegan package) was performed.

[0095] [Table 1]

[0096] [Table 2]

[0097] B-4 Multivariate analysis Multivariate analysis was performed on each sample based on the 35 sulfur-related compounds detected in B-3 above, and the silicon microparticle-administered group and the control group were able to be distinguished by the following 10 compounds. The results of the multivariate analysis of the silicon microparticle-administered group and the control group using the following 10 compounds (average values ​​of the analysis results for each of the two samples) are shown in Figure 8. Glutathione monosulfide (labeled) Cysteinylglycine (labeled) Thiosulfate ion (labeled) Hypotaurine 5-Glutamylcysteine ​​(labeled) Cysteine ​​monosulfide (labeled) S-sulfocysteine Sulfite ion (labeled) Serine Taurine

[0098] The above compounds include glutathione monosulfide and cysteine ​​monosulfide, which are involved in antioxidant effects in the body, and are thought to play a part in the antioxidant effect of silicon microparticles. Since no such report has been made about hydrogen, this may be one of the antioxidant effects unique to the preventive or therapeutic agent of the present invention.

[0099] B-5 Sulfur Index Analysis (2) A comparative analysis (n=6 / group) of the amounts of glutathione and glutathione monosulfide (Glutathione-S) in the large intestine was conducted using the colons of the silicon microparticle-administered group and the control group. The test methods were the same as those described above for B-1 to B-3. The results are shown in Figure 6. There was no difference in the amount of glutathione between the silicon microparticle-administered group and the control group, but the amount of glutathione monosulfide was significantly increased in the silicon microparticle-administered group. Glutathione monosulfide has strong antioxidant properties and is thought to play a part in the mechanism of action of silicon microparticles.

[0100] C. Pharmacological studies in models of attention-deficit hyperactivity disorder C-1. Creation of an ADHD model Five-day-old neonatal male mice (C57BL / 6JJmsSlc) were intraventricularly injected with desipramine (20 mg / kg), a selective noradrenaline reuptake inhibitor. Thirty minutes later, 6-hydroxydopamine (6-OHDA) (25 μg), a neurotoxin that selectively degenerates dopaminergic and noradrenergic neurons, was intraventricularly injected to create an attention deficit hyperactivity disorder model (Figure 7). The ventricle was injected 0.6 mm lateral to the sagittal suture, 2.0 mm rostral to the sagittal suture, and 1.3 mm deep from the skin. The injection was unilateral, not bilateral. Reference: Bouchatta O. et al., Sci Rep, 2018; 8: 15349

[0101] C-2. Silicon microparticle administration The mother and newborn mice were given a regular diet (Oriental Yeast Co., Ltd., model number AIN93M) and the silicon microparticle-containing diet obtained in I above in powder form, without solidification, so that they could eat them ad libitum. The regular diet or the silicon microparticle-containing diet was given to the mother and newborn mice from 3 days after birth until analysis at 24 days after birth.

[0102] C-3. Hyperactivity test using an open field At 24 days of age, mice were tested for hyperactivity in an open field (50 cm x 50 cm). The results are shown in Figure 8. The vertical axis in Figure 8 represents the total distance traveled in the open field over a 10-minute period. The group administered saline in addition to a normal diet showed normal activity levels, but the group administered 6-OHDA in addition to a normal diet showed a significant increase in activity levels and hyperactivity. In contrast, the group administered 6-OHDA in addition to a silicon microparticle-containing diet showed activity levels similar to those of the group administered saline in addition to a normal diet, and hyperactivity was significantly improved.

[0103] C-4. Neuroprotective effect Furthermore, at 25 days of age, the day after behavioral analysis, mice were perfusion-fixed, and their brains were cryosectioned and immunostained. In the normal diet group, saline administration demonstrated significant staining for tyrosine hydroxylase (TH), a marker of dopaminergic neurons, in the ventral tegmental area (VTA), substantia nigra pars compacta (SNc) (Figure 9), and striatum (Figure 10). In contrast, 6-OHDA administration demonstrated significantly reduced TH staining in the VTA, SNc (Figure 9), and striatum (Figure 10), suggesting dopaminergic neuronal dysfunction. However, in the group treated with 6-OHDA and silicon microparticles, TH staining in the VTA, SNc (Figure 9), and striatum (Figure 10) was comparable to that in the normal diet group, suggesting amelioration of dopaminergic neuronal dysfunction. These results demonstrate the efficacy of a silicon microparticle-containing diet for the treatment of attention-deficit hyperactivity disorder (ADHD).

[0104] From the above results, it is clear that the silicon microparticles of the present invention have a high preventive effect and a high therapeutic effect against attention deficit hyperactivity disorder. [Industrial Applicability]

[0105] This invention may be one of the causal therapies for attention deficit hyperactivity disorder, and will make a great contribution to future medical care and health promotion.

Claims

1. A preventive or therapeutic agent for attention deficit hyperactivity disorder, containing silicon microparticles.

2. The preventive or therapeutic agent according to claim 1, wherein the attention deficit hyperactivity disorder is hyperactivity in attention deficit hyperactivity disorder.

3. 3. The preventive or therapeutic agent according to claim 1, wherein the silicon microparticles are silicon-containing microparticles capable of generating hydrogen upon contact with water.

4. 4. The preventive or therapeutic agent according to claim 1, wherein the silicon-containing microparticles are microparticles containing simple silicon.

5. 5. The preventive or therapeutic agent according to claim 1, wherein the silicon microparticles have a silicon oxide film formed on the surface thereof.

6. The preventive or therapeutic agent according to claim 5 , wherein the silicon oxide film is a silicon oxide film having a hydroxyl group added thereto.

7. The preventive or therapeutic agent according to any one of claims 1 to 6, wherein the silicon microparticles are silicon microparticles and / or aggregates of the silicon microparticles.

8. 8. The preventive or therapeutic agent according to claim 7, wherein the silicon microparticles are microparticles made of simple silicon and have a silicon oxide film formed on the surface thereof.

9. The preventive or therapeutic agent according to any one of claims 1 to 6, wherein the silicon microparticles are porous silicon particles.

10. The preventive or therapeutic agent according to any one of claims 1 to 9, wherein the silicon microparticles are silicon microparticles that have been hydrophilized.

11. The preventive or therapeutic agent according to any one of claims 1 to 10, which is for oral administration.

12. A pharmaceutical composition for preventing or treating attention deficit hyperactivity disorder, comprising the prophylactic or therapeutic agent according to any one of claims 1 to 11.

13. A food or drink for preventing or treating attention deficit hyperactivity disorder, comprising the prophylactic or therapeutic agent according to any one of claims 1 to 11.

Images