TW202228732A - Oxidative stress inhibitor and antioxidant agent - Google Patents

Abstract

An oxidative stress inhibitor 100 of the present invention comprises silicon particles capable of generating hydrogen. In a preferred embodiment of this oxidative stress inhibitor 100, the following effects (a) and/or (b) can be achieved. (a) Increasing the total generation amount (total synthesis amount). (b) Relating to hydrogen generation amount per unit time (namely, hydrogen generation speed), elevating the hydrogen generation speed especially at the initial stage.

Description

Oxidative Stress Inhibitors and Antioxidants

The present invention relates to oxidative stress inhibitors and antioxidants.

Hydrogen is widely used and there are also a number of anticipated uses. As one example, there have been publications about oxidative stress as a cause of objects and growth. For example, reactive oxygen species exist in the human body, which are generated by metabolism in mitochondria in cells, subcutaneously generated under ultraviolet irradiation, or derived from oxygen inhaled from the lungs. Active oxygen is necessary for sustaining life, and on the other hand, it is known to cause damage to cells constituting an organism by oxidizing it. In particular, the hydroxyl group with the strongest oxidative power among the reactive oxygen species is thought to cause various diseases such as cancer, cerebral infarction, myocardial infarction, diabetes and other lifestyle diseases, skin aging and skin disorders such as dermatitis. Therefore, it is desirable that the remaining reactive oxygen species, especially hydroxyl groups, that are not used for reactions beneficial to the living body are not present in the body as much as possible.

If only attention is paid to the oxidative stress in the living body, the hydroxyl group produced in the body will be destroyed by the reaction with several substances. As examples of substances that eliminate hydroxyl groups, it is generally inferred that polyphenols, vitamin C, α-tocopherol, and glutathione are antioxidant substances that exist in vivo. However, these substances destroy not only hydroxyl groups, but also reactive oxygen species such as hydrogen peroxide, which function in the body, and may lead to disadvantages (side effects) such as decreased immunity. It is also known that hydrogen can also eliminate hydroxyl groups. However, among active oxygen species, hydrogen only reacts with hydroxyl groups, and thus does not cause the above-mentioned disadvantages (side effects). Then, there has been proposed an apparatus for producing hydrogen water containing hydrogen that eliminates hydroxyl groups in the body (for example, Patent Document 1).

However, the solubility of hydrogen (H ₂ ) in water at 25°C is extremely low, with a saturation solubility of 1.6 ppm, and hydrogen in hydrogen water is easily diffused into the air. Therefore, in order to take in an amount of hydrogen required for the elimination of hydroxyl groups into the body, it is necessary to keep the dissolved hydrogen concentration of the hydrogen water at a high level. Therefore, in the method of ingesting hydrogen water, it is impossible to ingest a sufficient amount of hydrogen to react with hydroxyl groups in the body. Therefore, a hydrogen-containing composition containing hydrogen and a surfactant has been proposed in order to easily take in hydrogen into the body (Patent Document 2), but the hydrogen concentration in the body cannot be maintained at a high level for a long time. Hydroxyl groups have high reactivity and immediately oxidize cells and are continuously produced in the living body. Therefore, in order to eliminate them, it is necessary to continuously supply high-concentration hydrogen into the body.

In view of the above-mentioned background, a solid preparation containing silicon microparticles as a main component, having high hydrogen-generating ability, and being orally administered has been disclosed (Patent Document 3). Another person discloses a composite material comprising silicon microparticles and silicon suboxide (SiOx, where _x is 1/2, 1 and 3/2) and/or covering at least a part of the surface of the silicon microparticles. Or a mixed composition of this suboxide and silica (Patent Document 4). [PRIOR ART DOCUMENTS] [PATENT DOCUMENTS]

[Patent Document 1] Japanese Patent No. 5514140 [Patent Document 2] Japanese Patent Application Laid-Open No. 2015-113331 [Patent Document 3] International Publication WO2017/130709 [Patent Document 4] International Publication WO2019/211960 [Patent Document 5] International Publication WO2018/037752 [Patent Document 6] International Publication WO2018/037818 [Patent Document 7] International Publication WO2018/037819 [Non-patent literature] [Non-Patent Document 1]

Matsuda et al., Water Splitting and Hydrogen Concentration with Silicon Nanoparticles, 62nd Spring Symposium of Applied Physics Society, Lecture Preprint, 2015, 12-031 [Non-Patent Document 2] Fujie et al., Hydrogen Production by the Reaction of Silicon Nanoparticles with Neutral Water, 64th Spring Symposium of Applied Physics Society, Lecture Preprint, 2015, 15a-421-6

[The problem to be solved by the invention]

However, even if hydrogen water is ingested, the amount of hydrogen contained in 1 liter of hydrogen water at 25°C is not more than 18 ml in gas conversion. In addition, hydrogen is the smallest molecule, and it is light and has a fast diffusion rate, so it is impossible to completely store it in a container containing the hydrogen water. Taking the example of in vivo use as an example, most of the hydrogen in the hydrogen water in the stomach is gasified. Therefore, a sufficient amount of hydrogen cannot be taken into the body, and there is a problem of causing the symptoms of suffocation (so-called "hiccups"). Therefore, according to conventional information, it is impossible to maintain a high hydrogen concentration in the body for a long time by ingesting hydrogen water, and to ingest it intermittently and continuously for a long time multiple times. On the other hand, in the case of ingesting a hydrogen-containing composition containing hydrogen by a surfactant, it is impossible to ingest a sufficient amount of hydrogen into the body for a long time by ingesting the hydrogen-containing composition. In addition, the problem of releasing hydrogen in the stomach as described above also occurs. Furthermore, in the case of using it on the skin, since it is used in the atmosphere, hydrogen diffuses into the atmosphere at an extremely fast diffusion rate faster than in the body and escapes in a short time, so it is difficult to absorb from the skin. In addition, there is still room for improvement in at least the generation amount and the generation speed of the disclosed technology for generating hydrogen using silicon microparticles.

In addition, the oxidative stress in the human body caused by the above-mentioned hydroxyl group is considered to be one of the causes of human aging. Therefore, the prevention or improvement of human aging is not only beneficial to individuals by extending the healthy lifespan of human beings, but also greatly contributes to the improvement of the national medical economy represented by social insurance premiums such as medical expenses. [Means to solve the problem]

The present invention solves at least one of the above-mentioned technical problems, and makes a great contribution to further enhancing the hydrogen production capacity (generation energy) possessed by silicon particles or silicon microparticles. For example, it has a great contribution to the rapid production of a large amount of hydrogen in the human body or various spaces containing water or water-containing liquids according to the situation, or to extract a large amount of hydrogen more reliably.

The inventors of the present application have repeatedly conducted detailed studies and analyses in order to achieve improvement of human constitution, promotion of health, and treatment or prevention of various diseases by utilizing substances with high hydrogen-producing ability. Regarding the production of hydrogen, among the total production (total production amount) and the hydrogen production amount per unit time (that is, the hydrogen production rate), a material design that considers the hydrogen production rate in the early stage is particularly required. Therefore, in order to improve the hydrogen production capacity, the inventors of the present application are not limited to "silicon microparticles" whose main particles are particles whose average crystal seed diameter is below the micrometer level, specifically, particles whose crystal seed diameter is more than 1 nm and less than 1 μm, but also include average crystals. Seed "silicon particles" with a diameter of 1μm or more, and seek a substance that can exert high hydrogen production capacity for research and analysis.

Therefore, the inventors of the present application attempted to manufacture silicon particles or silicon microparticles (hereinafter collectively referred to as "silicon particles") by a method different from the manufacturing method employed so far. As one specific example, the different manufacturing method is a manufacturing method including a classification step for obtaining silicon particles having a larger size and a fixed seed diameter after the step of pulverizing the silicon particles. In addition, as an example of another manufacturing method, the inventors of the present application conducted research on the influence of silicon (Si) as one of the requirements and including other elements in order to improve the hydrogen production capability. By adopting these production methods, research and analysis are conducted to find substances that can exhibit high hydrogen-producing ability.

As a result of experiments and analysis conducted by the inventors of the present application, it was found that silicon particles with hydrogen-generating ability can exert an effect as an oxidative stress inhibitor. More preferably, the silicon particles include silicon particles with a crystal seed diameter of 1 nm or more and 500 μm or less. Then, it was found that the hydrogen-generating capacity can be further enhanced compared to the past, especially by using silicon particles having the following characteristics (1) and/or (2). (1) The ratio of the silicon microparticles and the aggregates of the silicon microparticles with a crystal seed diameter of less than 1 μm to all the silicon particles, the silicon microparticles, and the aggregates is 5 mass % or less. (2) Metals that are supported, attached, or adsorbed on the surface of the aforementioned silicon particles or at least a part of the surface of the silicon microparticles, or are chemically bonded to the surface and are physiologically or medically permissible metals (hereinafter collectively referred to as "" Physiologically acceptable metals”), more specifically iron (Fe) or iron (Fe)-containing substances (hereinafter collectively referred to as “iron (Fe)”).

More specifically, the inventors of the present application found that by adopting the above (1) and/or (2), the total hydrogen production amount (total production amount) of the silicon particles and/or the hydrogen production amount per unit time in the initial stage These characteristics are greatly superior to those of conventional silicon microparticles.

In addition, if the analysis results of the above-mentioned (1) silicon particles by the present inventors are further described in detail, among the above-mentioned (1) silicon particles, the silicon particles (and the aggregates) as a whole are less than 1 μm in size. Since the existence ratio of the particles and the aggregates is low, the hydrogen-producing ability can be maintained at a high level, and the crystal seed diameter can be concentrated within a certain range, whereby a more stable hydrogen-producing ability can be exhibited. In addition, in the case of oral ingestion, the deterioration of human taste can be suppressed. It can also prevent silicon particles from being directly absorbed and infiltrated into blood vessels with a high degree of certainty.

Furthermore, if the analysis result of the above-mentioned (2) of the present inventors of the silicon particle is described in more detail, the specific metal is supported, adhered or adsorbed on the surface of the silicon particle or at least a part of the surface of the silicon microparticle, or the The results of the analysis of the hydrogen production capacity of the silicon particles whose surface is chemically bonded to the metal shows that the silicon particles further enhance the hydrogen production capacity. Then, by using the silicon particles of the above-mentioned (2) to increase the amount of hydrogen production, the following meaningful insight was obtained: after the hydrogen production reaction, suboxide (SiO _x , where where x is 1/2, 1 and 3/2; the same below) the film thickness, and/or the film thickness of the mixed composition of silicon oxide and silicon dioxide is larger than the film thickness of the conventional silicon microparticles. In addition, it is particularly worth noting that even if the silicon particles of the above (2) are the silicon particles of the above (1) containing larger particles, a strong hydrogen production energy can be generated. In addition, in this case, when the silicon particle has a sub-silicon oxide film covering at least a part of the surface of the silicon fine particle or the silicon particle, the silicon particle has the mixed composition film of the silicon sub-oxide and silicon dioxide, or In the case where the silicon particle has a natural oxide film, the "surface" of the silicon particle means the surface of the sub-silicon oxide film, the surface of the mixed composition film, or the surface of the natural oxide film, respectively.

The present invention has been created from the above-mentioned viewpoints.

In addition, the "silicon microparticles" in this case are mainly particles having an average crystal seed diameter of 1 nm or more and less than 1 μm. In a narrower sense, the "silicon microparticles" in this case have an average crystal seed diameter of the nanometer scale. Specifically, silicon nanoparticles with a crystal seed diameter of 1 nm or more and 500 nm or less are used as the main particles. In addition, the "silicon particles" in this case are mainly particles having an average crystal seed diameter exceeding 500 nm (in a narrower sense, 1 μm or more) and 500 μm or less.

In addition, the "silicon microparticles" in this case not only refer to individual silicon microparticles in a dispersed state, but also include a state in which a plurality of silicon microparticles aggregate to form agglomerates of the order of μm (about 0.1 μm or more). In addition, each said numerical range of "silicon fine particle" is only an example, and the numerical range is not limited. In addition, the crystal seed diameter can be appropriately selected according to the application, usage method, required function, and the like of the "silicon microparticles" or "silicon particles".

In addition, the "aqueous liquid" in this case refers to water or an aqueous solution, and includes, for example, human digestive tract internal fluid. In addition, "gastrointestinal fluid" refers to the fluid in the small intestine and the fluid in the large intestine. In addition, of course, the example of "aqueous liquid" is not limited to the above-mentioned example. In addition, the material of the "pH adjuster" in this case is not particularly limited as long as it is a chemical (hereinafter referred to as "alkali agent") that can adjust the pH value to an alkaline region exceeding 7 (representatively, exceeding 7.4) . In addition, use on human skin is also included.

In addition, when using the oxidative stress inhibitor of the present invention, which will be described later, as a drug for neutralizing active oxygen in the living body, it is preferable to use a drug that is recognized as a pharmaceutical (prescription drug), a quasi drug, or a food additive. Alkaline agent. Examples of the alkaline agent include sodium bicarbonate, sodium carbonate, sodium dihydrogen phosphate, disodium hydrogen phosphate, potassium bicarbonate, potassium carbonate, and other pH adjusters such as pharmaceuticals, medicated cosmetics, or food. Among them, the most common sodium bicarbonate is widely used as pharmaceuticals, medicated cosmetics or food additives, and it has the advantages of pH adjustment function, safety and versatility required by the present invention. In any of the pH adjusters, it is preferable to have a form that is not decomposed by an acid. In particular, in the case of oral ingestion of the oxidative stress inhibitor of the present invention, it is preferable to be in a form that is not decomposed by gastric acid or is not easily decomposed.

An oxidative stress inhibitor of one aspect of the present invention includes silicon particles and silicon microparticles having hydrogen generating ability.

According to this oxidative stress inhibitor, the oxidative stress in the human body caused by the hydroxyl group can be suppressed. In addition, a preferred aspect of the oxidative stress inhibitor can exhibit at least one of the effects of the following (a) to (c). (a) Increase in total production (total production) (b) Among the hydrogen production amount per unit time (that is, the hydrogen production rate), the hydrogen production rate in the initial stage is particularly increased (c) In the case of oral ingestion, silicon particles can be prevented from being directly absorbed and infiltrated into blood vessels with a high degree of certainty

In addition, for example, in the above-mentioned invention, among the above-mentioned silicon particles, the proportion of the silicon microparticles having a crystal seed diameter of less than 1 μm and the aggregates of the silicon microparticles relative to all the silicon particles, the silicon microparticles, and the aggregates thereof The oxidative stress inhibitor of 5 mass % or less (more preferably 3 mass % or less, still more preferably 1 mass % or less, still more preferably 0.5 mass % or less, still more preferably 0.2 mass % or less) can be more reliably exerted At least one of the effects of (a) to (c) above.

In addition, for example, in the above-mentioned invention, the above-mentioned oxidative stress inhibitor further comprises iron which is carried, attached or adsorbed on the surface of the above-mentioned silicon particles or at least a part of the surface of the above-mentioned silicon microparticles, or is chemically bonded to the surface. (Fe), and at least one of the above-mentioned effects (a) to (c) can be exhibited with a high degree of certainty.

Here, although the detailed mechanism has not yet been clarified, due to the support, attachment or adsorption of metal elements (hereinafter collectively referred to as "support"), and the catalytic action of the metal element increases the amount of hydrogen production. After the reaction, the thickness of the silicon suboxide coating at least a part of the surface of the silicon microparticles or the silicon particles and/or the film thickness of the mixed composition of the suboxide and silicon dioxide can be made larger than that of the conventional silicon microparticles. That is, by using this oxidative stress inhibitor, silicon is contacted with water (or water in an aqueous solution) to form hydrogen, whereby the reaction to form silicon oxide can occur with a higher degree of certainty. As a result, compared to silicon particles or silicon microparticles that are hardly supported (or not supported at all), or are almost not chemically bonded to the metal element (or are not chemically bonded at all), the performance is more excellent. hydrogen production capacity. In addition, it is worth mentioning that even silicon particles with a crystal seed diameter of 1 μm or more, which are relatively large particles, can produce a strong hydrogen production capacity.

In addition, according to the research and analysis of the inventors of the present invention, the oxidative stress inhibitor of the present invention is helpful to maintain or even improve human health, or prevent or even improve human aging, which can be used, for example, to prevent or improve Nutritional supplements, foods (including food additives and health foods) for the diseases or symptoms (including symptoms) of the following (1) to (5), or the prevention or treatment of the following (1) to (5) The function of the preparation of a disease or symptom (including symptoms). (1) skin diseases (2) Itchy skin (3) Constipation or diarrhea (4) hangover syndrome (5) Prevention or improvement of human aging

In addition, the above-mentioned "skin disease" includes at least one selected from the group consisting of eczema, inflammatory skin disease, skin barrier dysfunction allergic dermatitis, contact dermatitis, and atopic dermatitis. [Effect of invention]

An oxidation stress inhibitor according to one aspect of the present invention is an oxidation pressure inhibitor excellent in the total amount of hydrogen production (total production amount) and/or the hydrogen production amount per unit time in the initial stage.

Embodiments of the present invention will be described in detail with reference to the drawings. In addition, when performing this description, unless otherwise stated, the common reference numerals are given to the common parts in all the drawings. In addition, the drawings do not necessarily show the requirements of the present embodiment to scale. In addition, in order to make each illustration easier to see, a part of the code|symbol is abbreviate|omitted.

[1] Oxidative stress inhibitor and method for producing the same <First Embodiment> The oxidative stress inhibitor 100 and the manufacturing method of the oxidative stress inhibitor 100 of the present embodiment will be described in detail. FIG. 1( a ) is a schematic diagram of the oxidative stress inhibitor 100 of the present embodiment. As shown in FIG. 1( a ), the oxidative stress inhibitor 100 of the present embodiment includes silicon particles or silicon microparticles (hereinafter collectively referred to as “silicon particles”) 10 having the ability to generate hydrogen.

In addition, in a preferred aspect of the oxidation stress inhibitor 100, the silicon particles 10 and the silicon microparticles 10 are included, and the silicon microparticles and the aggregates of the silicon microparticles whose crystal seed diameter is less than 1 μm are relative to all the silicon particles, The proportion of the silicon microparticles and these aggregates is 5 mass % or less (more preferably 3 mass % or less, still more preferably 1 mass % or less, still more preferably 0.5 mass % or less, still more preferably 0.2 mass % or less) . [Manufacturing method of oxidative stress inhibitor 100]

Next, the manufacturing method of the oxidative stress inhibitor 100 of this embodiment is demonstrated. The surface of the oxidation pressure inhibitor 100 and the silicon oxide film covering the surface measured or observed during the reaction of the oxidation pressure inhibitor 100 with the aqueous solution are also described. <Pulverization step>

In this embodiment, for example, commercially available high-purity silicon particle powder (particle size of 300 μm or less, purity of 99.999%, i-type silicon) is used as a part of the raw material of the oxidation stress inhibitor 100 . In addition, in another aspect of this embodiment, silicon particle powder with a purity higher or lower than the above-mentioned purity can be used.

First, a pulverization step (first pulverization step) is performed on the high-purity silicon particle powder by pulverization treatment using a cutter by a jet mill method. In addition, as a modification of the present embodiment, after the first pulverizing step, an additional pulverizing step (second pulverizing step) using 0.5 mmφ zirconia beads in ethanol is performed in a bead mill method, Silicon microparticles (silicon nanoparticles) 10 having a typical crystal seed diameter of less than 500 nm are obtained, which is also an applicable aspect. Furthermore, as an alternative to the first pulverization step, a ring roll milling method, a high-speed rotary pulverization method, or a container-driven milling method is used to obtain silicon particles 10 having a crystal seed diameter of 1 μm or more and 60 μm or less, or a representative crystal seed diameter. Silicon microparticles (silicon nanoparticles) 10 up to 500 nm are also applicable.

In addition, from the viewpoint of improving the hydrogen production capacity of the oxidation pressure inhibitor 100 containing the silicon particles 10 finally produced, in the case of performing the wet treatment in each of the above-mentioned pulverization steps, 99% or more ethanol (for example, 99.5% or more) is used. wt %) and a small amount of water (for example, 0.1 wt % or more and 10 wt % or less, more preferably more than 1 wt % and 2 wt % or less) mixed solution is a preferred aspect. <Grading procedure>

It is also an aspect of the present embodiment to perform the classification step between the pulverizing step (first pulverizing step or the second pulverizing step) of the present embodiment and the carrying step of the metal element described later. Specifically, using the air flow method, the ratio of the silicon microparticles 10 and the aggregates of the silicon microparticles 10 having a crystal seed diameter of less than 1 μm to all the silicon particles 10 , the silicon microparticles 10 , and the aggregates is 5% by mass. or less (more preferably 3 mass % or less, still more preferably 1 mass % or less, still more preferably 0.5 mass % or less, still more preferably 0.2 mass % or less), the silicon microparticles 10 and the crystal seed diameter of less than 1 μm are substantially removed. Aggregate of silicon microparticles 10 . In addition, unlike the term “crystal seed diameter” used for the silicon particles 10 , the “crystal particle diameter” is used as a term for the overall diameter of the aggregate of the silicon particles 10 .

The oxidative pressure inhibitor 100 with hydrogen generating ability of the present embodiment includes silicon particles 10 and silicon fine particles 10 , and the silicon fine particles 10 and the aggregates of the silicon fine particles 10 whose crystal seed diameter is less than 1 μm are relative to all the silicon particles 10 . , silicon microparticles 10 and the ratio of the aggregates of these are 5 mass % or less (more preferably 3 mass % or less, still more preferably 1 mass % or less, still more preferably 0.5 mass % or less, still more preferably 0.2 mass % or less ), the effect of improving safety by preventing the oxidative stress inhibitor 100 from passing through the cell membrane and between cells of the intestinal tract can be exhibited more reliably.

In addition, the upper limit of the crystal seed diameter of the silicon particles 10 and the aggregates of the silicon particles 10 is not limited as long as it has the ability to generate hydrogen. However, in addition to the above-mentioned classification step, a classification step of substantially removing the silicon particles 10 and the aggregates of the silicon particles 10 having a crystal seed diameter exceeding 60 μm or more preferably exceeding 45 μm may also be employed. More specifically, the ratio of the silicon particles and the aggregates of the silicon particles having a crystal seed diameter exceeding 60 μm (more preferably more than 45 μm) with respect to all the silicon particles and the aggregates may be 5 mass % or less (more The classification step of classification is preferably performed so as to be 3 mass % or less, more preferably 1 mass % or less, still more preferably 0.5 mass % or less, still more preferably 0.2 mass % or less. By roughly removing the silicon particles 10 and the aggregates of the silicon particles 10 with a crystal seed diameter exceeding 60 μm or more preferably more than 45 μm, the hydrogen production capacity can be maintained at a high level and the crystal seed diameter can be limited within a certain range, so that a better performance can be achieved. Stable hydrogen production capacity. In addition, in the case of oral ingestion, it is possible to suppress deterioration of human taste. In addition, silicon particles can be prevented from being directly absorbed and infiltrated into blood vessels with a high degree of certainty.

As a result, as an example, the ratio of the silicon microparticles and the aggregates of the silicon microparticles with a crystal seed diameter of less than 1 μm to all the silicon particles, the silicon microparticles, and the aggregates can be obtained to be 5 mass % or less (more It is preferably 3 mass % or less, more preferably 1 mass % or less, still more preferably 0.5 mass % or less, still more preferably 0.2 mass % or less) silicon particles 10 and aggregates of silicon particles 10 . Moreover, in another aspect, the silicon particle 10 and the aggregate of the silicon particle 10 can be obtained with a crystal seed diameter of 1 μm or more and 60 μm or less (more preferably, 1 μm or more and less than 45 μm).

The results of comparing the oxidative stress inhibitor 100 of the present embodiment with the silicon particles not subjected to the classification step of the present embodiment, as described above, from the realization of stable hydrogen production ability and the suppression of human taste during oral ingestion. The oxidative stress inhibitor 100 of this embodiment is excellent in terms of deterioration and reduction of the possibility of silicon particles infiltrating blood vessels. In addition, when the silicon particles not subjected to the classification step were reacted with an aqueous sodium bicarbonate solution (pH 8.3) at 37° C. for 48 hours, the amount of hydrogen produced was 295 mL/g. However, the hydrogen production rate of the oxidation pressure inhibitor 100 under the same conditions as above was 430 mL/g, which shows that the hydrogen production capacity of the oxidation pressure inhibitor 100 of this embodiment is significantly better.

By going through the above steps, the oxidative stress inhibitor 100 having the silicon particles 10 and the aggregates of the silicon particles 10 can be obtained. <Modification (1) of the first embodiment>

The oxidative stress inhibitor 200 of this modification example and the manufacturing method of the oxidative stress inhibitor 200 will be described in detail. FIG. 1( b ) is a schematic diagram of the oxidative stress inhibitor 200 of this modification. As shown in FIG. 1( b ), the oxidative stress inhibitor 200 of this modification includes: silicon particles or silicon microparticles (hereinafter collectively referred to as “silicon particles”) 10 , which have the ability to generate hydrogen; a physiologically acceptable metal element 20. It is carried, attached or adsorbed on the surface of the silicon particle 10 or at least a part of the surface of the silicon microparticle 10, or chemically bonded to the surface.

In addition, in this modification, the metal element 20 is iron (Fe). In addition, the state in which the metal element 20 is physically adsorbed on the silicon particle 10 is an example in which the metal element 20 is carried on the surface of the silicon particle 10 or the surface of the silicon fine particle 10 . On the other hand, a state in which a part of the metal element 20 is chemically adsorbed on the surface of the silicon particle 10 and a state in which a compound (such as a silicide) is formed in the region where the metal element 20 and the surface of the silicon particle 10 are in contact are silicon particles. An example of chemical bonding between the surface of 10 and the metal element 20 .

In addition, the amount of the metal element 20 carried on the surface of the silicon particle 10 or at least a part of the surface of the silicon fine particle 10, or the amount of the metal element 20 chemically bonded to the surface is not particularly limited. Typically, the amount of the metal element 20 is 0.1 ppmw or more and 1000 ppmw or less in terms of mass ratio. In addition, the amount of the metal element 20 is preferably 0.5 ppmw or more in terms of mass ratio ( More preferably 1 ppmw or more, more preferably 1.5 ppmw or more, still more preferably 2 ppmw or more), and the upper limit of the numerical range is preferably 500 ppmw or less (more preferably 300 ppmw or more, more preferably 100 ppmw or more, and even better 75ppmw or less, more preferably 50ppm or less). [Manufacturing method of oxidative stress inhibitor 200] <The step of supporting the metal element>

In the manufacturing method of the oxidation stress suppressor 200 of the present modification, compared with the manufacturing method of the oxidation stress suppressor 100 of the first embodiment, the following steps are further performed: the metal element 20 is supported, attached or adsorbed on the silicon particles The surface of 10 or the surface of silicon microparticles 10 is a step, or a chemical bonding step of chemically bonding the metal element 20 and the surface of the silicon particle 10 (hereinafter collectively referred to as "carrying step").

In an example of the supporting step of the present embodiment, a spray treatment is performed in the treatment chamber, and a spray device is used to spray a solution (for example, an aqueous chloride solution) of the metal element 20 (for example, iron (Fe)) on the silicon particles 10 under stirring. ). For example, a spraying step of spraying a 10 mM FeCl ₂ aqueous solution on the silicon particles 10 is performed. In addition, the solution of the metal element 20 is a part of the raw material of the oxidation stress inhibitor 200 .

The oxidative stress inhibitor 200 of this modification can be manufactured through the above-mentioned supporting step.

In addition, in another example of the carrying step of the present embodiment, another step of contacting the silicon particles 10 with the solution of the metal element 20 may be used instead of the above spraying step, or performed together with the spraying step. As an example of other specific steps, a step of immersing the silicon particles 10 in the solution of the metal element 20 manually or automatically by using a container for accommodating the solution of the metal element 20 can be adopted.

Furthermore, in another example of the carrying step of the present embodiment, the pulverization process can be performed using a SUS cutter in the pulverization step, whereby, for example, iron (Fe) The step of carrying, attaching or adsorbing on the surface of the silicon particle 10 or the surface of the silicon microparticle 10 . In this case, the above-mentioned pulverizing step can also function as the supporting step of the present embodiment. <Analysis of hydrogen production by contacting oxidative stress inhibitor 200 with aqueous solution>

Then, in order to analyze the total amount (total production amount) and hydrogen production rate (production rate) of hydrogen (H ₂ ) generated by performing the contact step of bringing the aqueous liquid into contact with the oxidation pressure inhibitor 200 , the present inventors made the oxidation pressure The inhibitor 200 is immersed in an aqueous solution (pH 8.2) at a temperature equivalent to human body temperature (37°C), and the aqueous solution is an aqueous solution containing sodium bicarbonate as a pH adjuster as a solute. <Example>

The following examples are given to describe the first embodiment in more detail, but the first embodiment is not limited to these examples. [Example 1]

In the first embodiment, the metal element 20 is carried on the surface of the silicon particle 10 or a part of the surface of the silicon microparticle 10 , or the oxidation stress inhibitor 200 is chemically bonded to the surface and the metal element 20 . In addition, the metal element 20 of Example 1 is iron (Fe). Moreover, regarding the mass ratio in Example 1, the metal element 20 with respect to the silicon particle 10 was about 10 ppmw. [Example 2]

The second embodiment is also the same as the first embodiment, in that the surface of the silicon particle 10 or a part of the surface of the silicon microparticle 10 carries the metal element 20 or the oxidation stress inhibitor 200 for chemically bonding the surface and the metal element 20 . In addition, the metal element 20 of Example 2 is iron (Fe). Moreover, regarding the mass ratio in Example 2, the metal element 20 with respect to the silicon particle 10 was about 5 ppmw.

In addition, as a comparative example, silicon particles produced through the same steps as in Example 1 were used except that the carrying step of the modification (1) of the first embodiment was not performed. In addition, in the comparative example, the metal relative to the silicon particles was less than 0.1 ppmw in terms of mass ratio, and in a more narrow sense, was below the detection limit when an inductively coupled plasma mass spectrometer was used.

FIG. 2 is a graph showing the time change of hydrogen generated by the reaction of the oxidative stress inhibitor 200 of the above-mentioned Example 1 and Example 2, and the silicon particle of the comparative example and an aqueous solution.

As shown in FIG. 2 , it can be clearly seen that among the oxidative stress suppressors 200, for Example 1, not only the hydrogen production amount (591 mL (ml)/g (g)) is high, but also after the hydrogen production ( In particular, within 2 to 3 hours after hydrogen production), the amount of hydrogen per unit mass (mL/g) is extremely high. Specifically, the amount of hydrogen production from 3 hours after the start of hydrogen production was about 385 mL/g, which was an extremely high value. In addition, it is worth mentioning that, as described in Example 1, high hydrogen production capability can be exhibited for a long period of 40 hours or more (at least 48 hours in one example) from the start of hydrogen production.

In addition, among the oxidative stress suppressors 200, with regard to Example 2, not only the total yield (368 mL/g) is large, but also the amount of hydrogen per unit mass (mL) after hydrogen production (in particular, within 2 to 3 hours after hydrogen production). /g) significantly more. Specifically, the amount of hydrogen production from 3 hours after the start of hydrogen production was about 170 mL/g, which was a relatively high value. In addition, it is worth mentioning that, as in Example 2, a high hydrogen production capability can be exhibited for a long period of 40 hours or more (at least 48 hours in one example) after the start of hydrogen production.

On the other hand, regarding the comparative example in which the supporting step of the first embodiment is not performed, it can be seen that not only is the amount of hydrogen production (309 mL/g) less than that of the oxidation pressure inhibitor 200, but also that after hydrogen production (especially hydrogen production) The amount of hydrogen per unit mass (mL/g) is the least within the next 2 to 3 hours. Specifically, the amount of hydrogen production from 3 hours after the start of hydrogen production was as low as about 75 mL/g.

In order to confirm the reproducibility, the inventors of the present application used iron (Fe) as the metal element 20 in the same manner as in Example 1, and set the mass ratio of the metal element 20 to the silicon particles 10 to about 0.5 ppmw, about 1.5 ppmw and About 2.0ppmw, the amount of hydrogen per unit mass (mL/g) in this case was investigated, and in either case, the amount of hydrogen per unit mass (especially within 2 to 3 hours after hydrogen production) was mL/g) (that is, the hydrogen production rate), all showed higher values than the comparative examples. In addition, it is interesting that in each of the above three mass ratios, the amount of hydrogen per unit mass (mL/g) after hydrogen production and the amount of hydrogen generated until the end of the hydrogen production reaction (mL/g) are all obtained. It can be said that it is the same value within the range of experimental error. <Analysis by Transmission Electron Microscope (TEM) Image>

Furthermore, the inventors of the present application used a transmission electron microscope (TEM) to analyze the reaction of the oxidative pressure inhibitor 200 of the above-mentioned Example 1 and the above-mentioned aqueous solution and the reaction of the silicon particles of the above-mentioned comparative example and the above-mentioned aqueous solution. A silicon oxide film covering the surface. FIG. 3 is a cross-sectional TEM image showing the film thickness of each silicon oxide in the oxidative stress inhibitor (a) of Example 1 and the comparative example (b).

Very interestingly, comparing FIG. 3( a ) with FIG. 3( b ), it can be confirmed that the silicon oxide film thickness (about 113.9 nm) of the oxidation stress inhibitor 200 of Example 1 is the silicon oxide film of the comparative example. Thicker (about 6.4nm) 17 times thicker. Although the detailed mechanism has not yet been clarified, it is believed that a part of the metal element 20 on the surface of the silicon particle 10 exerts a catalytic effect. As a result, compared with the case where the metal element 20 does not exist, the hydrogen production reaction is promoted, and as a result, it is considered that the film thickness of the suboxide and/or the film thickness of the mixed composition of the suboxide and silicon dioxide can be easily increased ( In other words, it is easy to produce hydrogen production reaction).

Therefore, the surface of the silicon particle 10 is coated by using the oxidation stress inhibitor 200 in which the surface of the silicon particle 10 or at least a part of the surface of the silicon microparticle 10 carries the metal element 20 or the surface is chemically bonded to the metal element 20 . The film thickness of at least a part of the sub-silicon oxide and/or the film thickness of the mixed composition of the sub-silicon oxide and the silicon dioxide becomes larger than the film thickness of the conventional silicon fine particles. The fact that the film thickness is increased indicates that the reaction between silicon and water (or water in an aqueous solution) to form silicon oxide and hydrogen can occur more reliably than conventional silicon fine particles.

As described above, regarding the mass ratio, by using the metal element 20 in a numerical range of at least 0.1 ppmw or more and 1000 ppmw or less with respect to the silicon particle 10, the surface of the silicon particle 10 or at least a part of the surface of the silicon fine particle 10 is supported, Alternatively, the oxidation pressure inhibitor 200 whose surface is chemically bonded to the metal element 20 within the range of the value can greatly contribute to further improving the hydrogen production capability of the oxidation pressure inhibitor 200 . For example, it is very helpful to generate a large amount of hydrogen rapidly and for a long time in response to conditions, or to extract a large amount of hydrogen with a higher degree of certainty, in the human body or in various water-containing spaces or aqueous fluids. <Modification (2) of the first embodiment>

After the pulverizing step in the above-mentioned first embodiment, or after the pulverizing step in the modification (1) of the first embodiment, and before the carrying step, the surface of the silicon particle 10 or the silicon fine particle is subjected to It is also a preferred aspect that the surface 10 is further contacted with hydrogen peroxide water to thereby perform a modification step of modifying the surface. By this modification step, the silicon particles including silicon nanoparticles can be made hydrophilic in macroscopic view. For example, the silicon particles can be immersed in hydrogen peroxide water (for example, about 10°C to about 80°C, about 20°C to about 50°C from the viewpoint of realizing lower cost) contained in a conventional container, Thereby, the modification step is performed.

In addition, according to the experiments of the present inventors, it was confirmed that compared with the case where the reforming step is performed with the above-mentioned hydrogen peroxide water, under the condition that the supporting step in the modification (1) of the first embodiment is not performed The amount of hydrogen production is larger in the oxidation stress inhibitor 200 in the modification (1) of the above-mentioned first embodiment (the step of reforming with hydrogen peroxide water is not performed).

In addition, the same modification can also be achieved by immersing the silicon particles in ozone water and/or sodium percarbonate instead of hydrogen peroxide water. Alternatively, the same modification can also be achieved by contacting the silicon particles with at least one selected from the group consisting of hydrogen peroxide water, ozone water and sodium percarbonate.

In addition, as described above, from the viewpoint of low cost and safe handling, it is also preferable to perform the reforming step using hydrogen peroxide water at about room temperature, and in the reforming step of the present modification, peroxide is used. Hydrogen water, like ethanol, can generate hydrogen by using materials that are safer and safer (for example, less harmful to the human body), which is also a better aspect from this point of view. <Modification (3) of the first embodiment>

In this modification, 500 mg of the oxidation stress inhibitors 100 and 200 of the first embodiment or modification (1) and (2) of the first embodiment and about 500 mg of sodium bicarbonate powder (Wako Pure Pharmaceutical Co., Ltd., purity 99.5%) mixed. This mixture is kneaded and used a tablet method to obtain a cylindrical block tablet (eg, a tablet for medicine or medicated cosmetic) having a seed diameter of about 8 mm and a height of about 4 mm. In addition, a lozenge is an example of a block preparation. In addition, nanocapsules, microcapsules, general capsules, or nanocapsules, microcapsules, general capsules, and other pH adjusters such as oxidative stress inhibitors 100, 200 and sodium bicarbonate, which have stable suboxide, do not dissolve in acidity but dissolve in alkalinity. It is a better aspect to carry out coating. By adopting the aforementioned aspect, the reaction in the presence of water in an acidic condition can be avoided, and the reaction in the presence of water in an alkali can be dissolved to promote the reaction of the oxidative stress inhibitors 100 and 200 with water. <Modification (4) of the first embodiment>

In addition, the oxidative stress inhibitors 100 and 200 of the first embodiment or the modifications (1) to (3) of the first embodiment described above can be applied, for example, as a preparation (for medicine) or a drug-containing cosmetic. In addition, its application example is not limited to a lozenge. For example, the same effect as the above-mentioned effect can be obtained when a capsule in which the powdery oxidative stress inhibitor 100, 200 is encapsulated in a capsule is used instead of a tablet. The oxidative stress inhibitor 100, 200 can generate a lot of hydrogen if it is not a lump but a powder with a large surface area, but can be easily ingested orally or anusly as a tablet or capsule. Moreover, by making into a tablet or a capsule, a lump can be maintained in the stomach to some extent, and on the other hand, it disintegrates after passing through the stomach and becomes a powder. Thus, the surface area of the oxidative stress inhibitor 100, 200 exposed to gastric juice and/or stomach contents can be reduced in the stomach where hydrogen production is to be inhibited, while the exposure can be increased in the small and/or large intestine where hydrogen production is to be promoted on the surface area of the aqueous liquid.

In addition, the oxidative stress inhibitor 100, 200 may be a granular preparation. Granular formulations, compared to lozenges or capsules, are powdery at an earlier stage after oral ingestion or ingestion through the anus. However, in the case of oral ingestion, since the pH of gastric juice is low (about 1.5), almost no hydrogen is generated even if it is in powder form immediately after reaching the stomach, but hydrogen is generated in the presence of water after passing through the stomach.

The oxidative stress inhibitor 100, 200 may also be a powder. In the case where the oxidative stress inhibitors 100 and 200 are used as constituents of foods including health foods, such as food additives, powders are easier to handle. When used as a food additive, as the oxidation stress inhibitor 100 and 200, silicon particles 10 with a crystal seed diameter of 1 nm or more and 10 μm or less, or 1 nm or more and 500 nm or less (more narrowly, 1 nm or more and 100 nm or less) can be used. Mixed use. Preferably, the silicon particles 10 are contained in an amount of 1 mass % or more. There is no upper limit on the content of the silicon particles 10 originally, but in consideration of taste, it is preferably 40 mass % or less.

Moreover, the example which can be applied to the coating layer of a tablet is a coating agent which coats the outermost layer of a tablet, that is, a known gastro-insoluble enteric material. In addition, an example which can be applied to the coating layer of a capsule is a capsule itself made of a known gastro-insoluble enteric material, which encloses the oxidative stress inhibitors 100 and 200 .

As described above, examples of preferable formulations as active examples of the oxidative stress inhibitors 100 and 200 are lozenges of bulk formulations that are easy to take orally or a sufficient amount from the anus, or powdered oxidized Capsules in which the pressure suppressants 100 and 200 (which may include those in a state of being agglomerated) are enclosed in capsules. In addition, when a tablet is used, a disintegrant may be further contained. Moreover, as a disintegrant, a well-known thing can be used. Furthermore, a more preferable example of the disintegrant is an organic acid, and the most preferable example is citric acid. Here, the organic acid may also function as a binding agent for making the silicon particles 10 bulky. In addition, the oxidative stress inhibitors 100 and 200 can also be applied as, for example, granular, flake, and/or shredded food ingredients (representatively, "pineapple") for each food material. <Modification (5) of the first embodiment>

In addition, the oxidative stress inhibitors 100 and 200 of the first embodiment or the modified examples (1) to (4) of the first embodiment described above can be obtained, for example, by using a The medium", the intake of hydrogen into the body (including the skin itself or the mucosa itself) through the skin or through the mucous membranes. In addition, the medium of this modification is not limited to a material or a commodity in particular. The effect of this modification can be exhibited as long as it is a physiologically acceptable medium. Therefore, those having the oxidative pressure inhibitors 100 and 200 and the medium in contact with the oxidative pressure inhibitors 100 and 200 can function as a hydrogen-donating material.

As one specific example, in a life situation, from the viewpoint of increasing the chance of human body parts coming into contact with water (or aqueous liquid) or a medium containing the water (or aqueous liquid) (hereinafter collectively referred to as "medium"), An example of a preferable medium is at least one selected from the group consisting of liquid, gel, cream, paste, emulsion, and mousse. Moreover, another example of a preferable medium is bath water (preferably alkaline bath water). Therefore, in one example of the present modification, a manufacturing method in which the bath water becomes a medium is produced.

As for the bath water, it is described in more detail that it is typically stored in tap water as bath water in general bathtubs (bathtubs including baths, public baths, and indoor or outdoor bathtubs installed in hotels). Before and after the bath water is stored, the above-mentioned oxidative stress inhibitor is placed or put into the bath, and the oxidative pressure inhibitors 100 and 200 are brought into contact with the bath water as a medium to perform a contact step, thereby generating hydrogen (H ₂ ). Therefore, the oxidative stress inhibitors 100 and 200 of this modification can also be used as a so-called bath agent.

Thus, the hydrogen (H ₂ ) produced by the above-mentioned contacting step can be brought into contact with the skin and/or mucous membranes of the bathed human body via the bath water as a physiologically acceptable medium. As a result, according to the present modification, the intake of hydrogen (H ₂ ) into the human body (including the skin itself or the mucous membrane itself) can be achieved using means different from oral intake or ingestion from the anus. <Example> [Example 3] [Effect of oxidative stress inhibitor on skin diseases]

FIG. 4 shows (a) images of the palm condition before ingestion of the oxidative stress inhibitor and (b) images of the palm condition 5 days after ingestion of the oxidative stress inhibitor of the subjects who confirmed the effect of the oxidative stress inhibitor.

In this example, as indicated by the arrows in Fig. 4(a), a volunteer subject (man in his 30s) with eczema and atopic dermatitis on the palm ingested 1 g of the oxidative stress inhibitor 100 orally every day. Then, the palm of the test subject was observed 5 days after the oxidative stress inhibitor ingestion. As shown in Fig. 4(b), a significant improvement effect was observed in both the symptoms of eczema and atopic dermatitis. Moreover, according to this test subject, the itching of the hand was also improved.

As shown in Fig. 4(b), the symptoms of hand eczema and atopic dermatitis were improved by taking the oxidative stress inhibitor continuously for only a few days. Specially mentioned effects. [Example 4] [Effect of oxidative stress inhibitor on constipation or diarrhea]

In this example, subjects (constipation: women in their twenties, women in their 40s, and women in their 60s) who had constipation symptoms or diarrhea symptoms with low frequency of laxation and who voluntarily participated in this example ingested 1 g per day orally. Oxidative Stress Inhibitor 100. Then, 5 days after the start of ingestion of the oxidative stress inhibitor, whether or not the subject's laxatives were improved or not, and/or the number of healthy bowel movements was checked, and as a result, an improvement effect was observed in any symptoms.

Therefore, it can be said that the effect of improving constipation and diarrhea can be obtained by taking an oxidative stress inhibitor. In addition, the oxidative stress inhibitor can function as a human intestinal environment improver or a human intestinal regulator. [Example 5] [Effect of oxidative stress inhibitor on hangover syndrome]

In this example, subjects (men in their 30s, men in their 40s, men in their 50s, men in their 60s) who voluntarily participated in this example of hangover syndrome (related physiological symptoms called "hangover") ) orally ingest 1 g of Oxidative Stress Inhibitor 100 per day. Then, after 2 days or more elapsed from the start of ingestion of the oxidative stress inhibitor, it was checked whether or not the hangover symptoms of the subject were improved, and as a result, an improvement effect was observed. In addition, "Hangover Syndrome" includes various phenomena such as nausea, vomiting, headache, lethargy, and decreased exercise capacity. In addition, it is widely known that acetaldehyde produced in the body when ingesting alcohol or after ingesting alcohol is the cause of hangover syndrome.

Therefore, it can be said that the effect of improving hangover syndrome can be obtained by taking an oxidative stress inhibitor. <Another embodiment (1)>

In addition, the oxidative stress inhibitors 100 and 200 of the above-described first embodiment or each modification of the first embodiment can also be used as nutritional supplements or food additives for humans. Therefore, a food containing the oxidative stress inhibitors 100 and 200 of the first embodiment or each modification of the first embodiment is also a preferable aspect that can be used. <Another embodiment (2)>

Furthermore, the oxidative stress inhibitors 100 and 200 of the first embodiment or each modification of the first embodiment described above aggregate in a natural state, so that the diameter and length dimension are on the order of μm (for example, several tens of μm or more). Aggregate. The oxidative stress inhibitor 100, 200 is artificially agglomerated by the addition and compression of such agglomerates or a binding agent, whereby a blend of bulk solid preparations having a size that can be picked up by a human finger can be formed. <Another embodiment (3)>

In addition, regarding the oxidative stress inhibitors 100 and 200 of the first embodiment or the modification examples of the first embodiment, for example, in the initial contact step (first contact step), the oxidative stress inhibitors 100 and 200 are brought into contact with a pH value of less than 7. The first aqueous liquid is brought into contact with the second aqueous liquid having a pH value of 7 or higher in the subsequent contact step (second contact step), and hydrogen can be generated in the second contact step. In addition, the oxidative stress inhibitors 100 and 200 of the above-mentioned embodiments have remarkable hydrogen-generating ability when contacted with an aqueous solution having a pH value of 7 or more (more preferably, more than 7, and even more preferably 8.2 or more).

In addition, the temperature conditions of the above-mentioned second aqueous solution for hydrogen production are not limited. Although it depends on the pH of the second aqueous solution, as long as the temperature of the second aqueous solution is 80° C. or lower, hydrogen production can be promoted with a high degree of certainty. However, the upper limit of the temperature of the second aqueous liquid is not originally limited. For example, when the oxidative stress inhibitors 100 and 200 of the above-described embodiments and their modifications are used as industrial chemicals, the temperature may exceed 50°C. However, the higher the temperature, the higher the heat resistance required for the equipment (including the container), and this problem must be paid attention to in handling. Therefore, when used as an industrial chemical, it is preferably used at 100°C or lower.

In addition, in the above-mentioned embodiments, nutritional supplements, foods (including food additives and health foods), foods (including food additives and health foods), Or it is a part of the function of the preparation for preventing or treating the diseases or symptoms (including symptoms) of the following (1) to (5), but the oxidative stress inhibitor 100 of the above-mentioned first embodiment or each modification thereof , 200, nutritional supplements, foods (including food additives and health foods), or used to prevent or improve all diseases or symptoms (including symptoms) of the following (1) to (5), or to prevent Or the function of a preparation for treating the diseases or symptoms (including symptoms) of the following (1) to (5). (1) skin diseases (2) Itchy skin (3) Constipation or diarrhea (4) hangover syndrome (5) Prevention or improvement of human aging

In addition, the oxidative stress inhibitors 100 and 200 of the above-described embodiments and their modifications can function as antioxidants or anti-aging (or improving) agents. Therefore, in the specification of the present application, the oxidative stress inhibitors 100 and 200 can be rewritten as antioxidants 100 and 200 , hydroxyl inhibitors 100 and 200 , or aging prevention (or improvement) agents 100 and 200 . <Another embodiment (4)>

Therefore, other technical ideas developed from the above-described first embodiment or each modification of the first embodiment include at least the following (A) to (F) in addition to the above-described technical ideas. (A) an antioxidant comprising silicon particles and silicon microparticles capable of producing hydrogen; (B) An antioxidant, in the aforementioned (A), the silicon microparticles with a crystal seed diameter of less than 1 μm and the aggregates of the silicon microparticles relative to all the silicon particles, the silicon microparticles, and the aggregates of these The proportion of the body is below 5% by mass; (C) An antioxidant, in the aforementioned (A) or (B), having a physiologically acceptable or medically acceptable metal element (iron (Fe)), which is carried, attached or adsorbed on the silicon particles; on the surface or at least a portion of the surface of the silicon microparticles, or chemically bonded to the surface; (D) a hydroxyl inhibitor comprising silicon particles and silicon microparticles capable of generating hydrogen; (E) A hydroxyl inhibitor, in the aforementioned (D), the silicon microparticles with a crystal seed diameter of less than 1 μm and the aggregates of the silicon microparticles are relative to all the silicon particles, the silicon microparticles, and the aggregates of these The proportion of the body is below 5% by mass; (F) a hydroxyl inhibitor, in the aforementioned (D) or (E), having a physiologically or medically acceptable metal element (iron (Fe)), which is carried, attached or adsorbed to the silicon On the surface of the particle or at least a portion of the surface of the silicon microparticle, or chemically bonded to the surface.

As a result, according to each modification of the above-mentioned first embodiment or the first embodiment, an antioxidant or a hydroxyl group inhibitor based on the above-mentioned (A) to (F) can be provided. <Another embodiment (5)>

Furthermore, in addition to the technical ideas developed from the first embodiment or the modified examples of the first embodiment, and the technical ideas disclosed in (A) to (F) of the other embodiment (4) described above In addition, the oxidative stress inhibitor, the antioxidant, and/or the hydroxyl inhibitor (in this embodiment, hereinafter collectively referred to as "antioxidants") can also be applied to the production method of antibody drugs. Therefore, in the present embodiment, in each step of the method for producing an antibody drug, an antioxidant including silicon particles having hydrogen-generating ability and silicon microparticles based on the above-mentioned technical ideas can be used.

Specifically, in the manufacturing method of the antibody drug of the present embodiment, the oxidative stress inhibitor, antioxidant, and/or hydroxyl inhibitor comprising the silicon particle with hydrogen-generating ability and the silicon microparticle are used as selected from the following At least one step in the group of steps (I) to (IV). (I) Preparation steps for antibody-producing cells and/or plasma cells of non-human animals, humans (limited to those ethically recognized or permitted, the same below), plants, fungi (coliform bacteria, etc.), or various eggs; (II) the separation step of the aforementioned antibody-producing cells and/or the aforementioned plasma cells; (III) a fusion tumor cell production step for producing fusion tumor cells; (IV) Monoclonal antibody production step for producing monoclonal antibody.

In the production step (I) above, for example, when immunizing a non-human animal, human, or plant to induce or induce an antibody response, the antioxidant of this embodiment can be used. The antioxidant can eliminate a part or substantially all of the hydroxyl groups generated in the preparation step, and can promote the induction or induction efficiency of the antibody response in the adjustment step.

In addition, examples of the above-mentioned "non-human animals" are selected from rats, mice, apes, sheep, goats, rabbits, camels, llamas, alpacas, llamas, guanacos, yaks, cows, musk deer At least one animal from the group of cattle, Tibetan antelope, raccoon, ferret, sable, raccoon, fox, horse, chinchilla, dog, pig and cat. Moreover, the example of the above-mentioned "plant" is at least one type of plant selected from the group consisting of rice, maize, and various wheats (barley, wheat, rye).

In the separation step (II) above, for example, antibody-producing cells (an example of B cells) and/or plasma cells are recovered from immunized non-human animals, humans, plants, fungi (coliform bacteria, etc.), or various eggs. (an example of B cells), the antioxidant of this embodiment can be used. The antibody-producing cells and/or the plasma cells produce hydroxyl groups, so that oxidative stress on the cells can cause damage, apoptosis, reduced function, and/or incomplete function of the cells. Therefore, the antioxidant can eliminate a part or substantially all of the hydroxyl groups generated in the separation step, thereby improving the recovery efficiency of the antibody-producing cells and/or the plasma cells in the separation step.

In the fusion tumor cell production step of the above (III), for example, fusion tumor cells ( When fused cells), the antioxidant of this embodiment can be used. Similar to the separation step in (II) above, the antibody-producing cells and/or the plasma cells will produce hydroxyl groups, so the application of oxidative stress to the cells will cause damage, apoptosis, reduced function and/or dysfunction of the cells. whole. Therefore, the antioxidant can eliminate part or substantially all of the hydroxyl groups produced in the fusion cell production step, thereby enhancing the production efficiency of the antibody producing cells and/or the plasma cells in the fusion cell production step.

In the monoclonal antibody production step of the above (IV), for example, the monoclonal antibody of this embodiment can be used when isolating a monoclonal antibody from a fusion tumor cell that produces an antibody specifically reactive with an antigen (including a peptide and a recombinant protein). Antioxidants. The antioxidant can eliminate part or substantially all of the hydroxyl groups generated in the monoclonal antibody production step, thereby helping to improve the function of the monoclonal antibody obtained in the monoclonal antibody production step, and/or improve the monoclonal antibody yield of the antibody.

In addition to the monoclonal antibody production step described above, the antioxidant of the present embodiment may be applied in the monoclonal antibody purification step in which the monoclonal antibody is purified. Therefore, a part or substantially all of the hydroxyl groups generated in the monoclonal antibody purification step can be eliminated, and the purification efficiency in the monoclonal antibody purification step can be improved.

In addition, in the case of producing a slightly neutral or weakly acidic solution preparation containing an antibody, a conventional tonicity agent (sugar or salt), a stabilizer, an emulsifier, etc., in each of the above steps, a liquid or a solution is used. In the step (representatively, an aqueous solution) (hereinafter collectively referred to as "solution"), the following methods can be employed.

Specifically, the solution may be impermeable to the medium, the coating, the support, or the holder, that is, the antioxidant (eg, the antioxidant in a granular or agglomerate form) may be directly contacted with the solution.

In another example, a bag body composed of a mesh filter through which only the solution can pass and containing the antioxidant to prevent the antioxidant from diffusing into the solution may be placed in contact with the solution (eg, by placing in the container containing the solution). In addition, the antioxidant in this example uses the classification step in the first embodiment to adjust the seed diameter distribution of the antioxidant to be a preferred aspect.

Furthermore, in another example, as an alternative to the aforementioned bag body, a non-woven fabric containing the antioxidant in a part of the surface and/or the interior (for example, a part or all of the non-woven fabric shown in Japanese Design Registration No. 1561310) can be used. In addition, in any of the above-mentioned cases, the bag body or the non-woven fabric is used in a clean state subjected to sterilization treatment or the like.

In addition, in a conventional biomass reactor, the antioxidant (eg, the antioxidant in granular or agglomerate form) can also be used. <Another embodiment (6)>

Moreover, in addition to the technical ideas developed by the above-mentioned first embodiment or each modification of the first embodiment, and those disclosed in (A) to (F) of the above-mentioned other embodiment (4) In addition to the technical idea, when culturing cells in the in vitro fertilization/embryo transfer method, or culturing at least one cell selected from the group of ES cells, iPS cells (induced pluripotent stem cells), and somatic stem cells, it is also possible to The oxidative stress inhibitor, the antioxidant and/or the hydroxyl inhibitor (hereinafter collectively referred to as "antioxidant" in this embodiment) are applied.

For example, when the above-mentioned cells are cultured, oxidative stress is exerted on the cells due to the production of hydroxyl groups by the cells, thereby causing damage, apoptosis, functional reduction and/or insufficiency of the cells. Therefore, the antioxidant can eliminate a part or substantially all of the hydroxyl groups produced by the cell, thereby enhancing the production efficiency or productivity of the cell.

Specifically, as in the other embodiment (5), in the step of using a liquid or a solution (representatively, an aqueous solution) (hereinafter collectively referred to as "solution") in the process of culturing each cell described above, a the following method.

The antioxidant (eg, the antioxidant in granular or bulk form) can be brought into direct contact with the solution (eg, in vitro development broth).

In another example, a bag body composed of a mesh filter through which only the solution can pass and containing the antioxidant to prevent the antioxidant from diffusing into the solution may be placed in contact with the solution (eg, by placing in the container containing the solution). In addition, for the antioxidant in this example, the grading step in the first embodiment is used to adjust the seed diameter distribution of the antioxidant to a preferred aspect.

Furthermore, in another example, as an alternative to the aforementioned bag body, a non-woven fabric containing the antioxidant on a part of the surface and/or the interior (for example, a part or all of the non-woven fabric shown in Japanese Design Registration No. 1561310) can be used. . In addition, in any of the above-mentioned cases, the bag body or the non-woven fabric is used in a clean state subjected to sterilization treatment or the like.

As described above, the disclosure of each of the above-described embodiments and their modifications is described for describing these embodiments or modifications, and is not intended to limit the present invention. In addition, other combinations of the embodiments and their modifications, and other modifications within the scope of the present invention are also included in the scope of the patent application. [Industrial Availability]

The oxidative stress inhibitor of the present invention can be widely used in various industries, including pharmaceuticals (including medicated cosmetics) using hydrogen, the medical industry, and the food industry.

10: Silicon particles, silicon microparticles 20: Metal Elements 100, 200: Oxidative stress inhibitors, antioxidants, hydroxyl inhibitors, age-preventing (or improving) agents

1 is a schematic diagram (a) of the oxidative stress inhibitor of the first embodiment and a schematic diagram (b) of the oxidative stress inhibitor of the modification (1) of the first embodiment. FIG. 2 is a graph showing the temporal change of hydrogen produced by the reaction of the oxidative pressure inhibitors of Example 1 and Example 2, and the comparative example with an aqueous solution. 3 is a cross-sectional TEM image showing the respective silicon oxide film thicknesses of the oxidation stress inhibitor (a) of Example 1 and the comparative example (b). Fig. 4 is a graph showing (a) images of the condition of the palm before ingestion of the oxidative stress inhibitor and (b) images of the palm after ingesting 1 g of the oxidative stress inhibitor daily for 5 days in subjects who confirmed the effect of the oxidative stress inhibitor image of the situation.

10: Silicon particles, silicon microparticles

20: Metal Elements

100,200: Oxidative stress inhibitor, antioxidant, hydroxyl inhibitor, ageing preventive (or improving) agent

Claims (14)

An oxidative stress inhibitor comprising silicon particles and silicon microparticles capable of producing hydrogen. The oxidative stress inhibitor of claim 1, wherein the ratio of the silicon microparticles and the aggregates of the silicon microparticles with a crystal seed diameter of less than 1 μm to all the silicon particles, the silicon microparticles and the aggregates is 5 mass % or less. The oxidative stress inhibitor according to claim 1 or 2, comprising iron (Fe) supported, attached or adsorbed on the surface of the silicon particle or at least a part of the surface of the silicon particle, or chemically bonded to the surface . The oxidation stress inhibitor according to claim 3, wherein the mass ratio of the iron (Fe) is 0.1 ppmw or more and 1000 ppmw or less, when the silicon particle or the silicon fine particle is set to 1. The oxidation stress inhibitor according to claim 3, wherein the mass ratio of the iron (Fe) is 0.5 ppmw or more and 1000 ppmw or less, when the silicon particles or the silicon fine particles are set to 1. A nutritional supplement containing the oxidative stress inhibitor of any one of claims 1 to 5. A nutritional supplement for preventing or improving skin diseases, which contains the oxidative stress inhibitor according to any one of claims 1 to 5. The nutritional supplement for preventing or improving skin diseases according to claim 7, wherein the aforementioned skin diseases are selected from the group of eczema, inflammatory skin diseases, skin barrier dysfunction, allergic dermatitis, and atopic dermatitis at least one of. A nutritional supplement for preventing or improving constipation, diarrhea or hangover syndrome, which contains the oxidative stress inhibitor according to any one of claims 1 to 5. A nutritional supplement for preventing or improving aging, which contains the oxidative stress inhibitor according to any one of claims 1 to 5. A food product containing the oxidative stress inhibitor as claimed in any one of claims 1 to 5. An antioxidant comprising silicon particles and silicon microparticles with hydrogen-generating ability. The antioxidant of claim 12, wherein the proportion of the silicon microparticles and the aggregates of the silicon microparticles with a crystal seed diameter of less than 1 μm relative to all the silicon particles, the silicon microparticles, and the aggregates is 5% by mass the following. The antioxidant of claim 12 or 13, which has iron (Fe) supported, attached or adsorbed on the surface of the silicon particle or at least a part of the surface of the silicon microparticle, or chemically bonded to the surface.

Images