Biodegradable magnesium or magnesium oxide–nanometal catalyst composite particles for reactive oxygen species control and uses thereof

Abstract

The present invention relates to a nano-metal composite particle comprising magnesium oxide and manganese oxide, a use of the composite particle as a nanozyme utilizing the ability to scavenge reactive oxygen species, and a manufacturing method therefor.

Description

Biodegradable magnesium or magnesium oxide-nanometal catalyst composite particles for controlling active oxygen and their use

[0001] The present invention relates to a magnesium or magnesium oxide-nanometal catalyst composite particle having biodegradable properties for controlling active oxygen and a nanozyme for capturing active oxygen using the same.

[0002]

[0003] Reactive oxygen species (ROS) are chemically reactive molecules containing oxygen atoms. ROS are primarily generated in mitochondria, tiny organelles within cells, and are a general term for various types of oxygen that are more unstable and reactive than ordinary oxygen used in the body. ROS are involved in signaling related to cell proliferation and differentiation, but higher levels are known to promote cancer development and metastasis, DNA damage, and cell death.

[0004] Therefore, scavenging these reactive oxygen species is emerging as a powerful therapeutic strategy for various diseases, and catalysts that can act as reactive oxygen species scavengers are called catalysts. Enzymes, in particular, are biocatalysts and are used in various fields due to their excellent substrate specificity and high catalytic reaction efficiency. However, enzymes are mainly composed of proteins and some nucleic acids, so they require stringent reaction conditions identical to those in a mild biological environment, such as appropriate temperature, pH, and temperature. They are also difficult to manufacture and purify, have low stability, and their activity can vary significantly depending on the surrounding environment. Therefore, nanozymes, nanoparticles with reactive oxygen species scavenging properties that can replace enzymes, are being actively researched recently.

[0005] Nanozymes offer several advantages compared to natural enzymes, including relative ease of manufacture, low cost, and stability against denaturation. However, most highly active metal nanomaterials can be biologically toxic. If not broken down in the body, they persist for long periods, generating byproducts that can generate reactive oxygen species or accumulate in organs, potentially posing significant challenges to their clinical applications. Therefore, research is urgently needed to address these shortcomings of nanozymes.

[0006]

[0007] Accordingly, the inventors of the present invention completed the present invention of a magnesium oxide-nano metal composite particle and a nanozyme using the same by utilizing the characteristics of magnesium, which has biodegradable properties, and manganese, which has excellent ability to capture reactive oxygen species (ROS), while conducting research on a nanozyme capable of capturing reactive oxygen species even in small amounts.

[0008] Therefore, the purpose of the present invention is to provide nano metal composite particles comprising magnesium oxide and manganese oxide.

[0009] Another object of the present invention is to provide a nanozyme comprising nano metal composite particles including magnesium oxide and manganese oxide.

[0010] Another object of the present invention is to provide a preventive or therapeutic agent for inflammatory diseases comprising nano metal composite particles comprising magnesium oxide and manganese oxide.

[0011] Another object of the present invention is to provide a method for producing nano metal composite particles comprising the magnesium oxide and manganese oxide.

[0012]

[0013] To achieve the above purpose, the present invention provides nano metal composite particles including magnesium oxide and manganese oxide.

[0014] In order to achieve another object of the present invention, the present invention provides a nanozyme comprising nano metal composite particles including magnesium oxide and manganese oxide.

[0015] In order to achieve another object of the present invention, the present invention provides an agent for preventing or treating an inflammatory disease, which comprises nano metal composite particles comprising magnesium oxide and manganese oxide.

[0016] In order to achieve another object of the present invention, the present invention provides a method for producing nano metal composite particles comprising the magnesium oxide and manganese oxide.

[0017]

[0018] Hereinafter, the present invention will be described in detail.

[0019] As one aspect of the present invention, the present invention relates to nano metal composite particles comprising magnesium oxide and manganese oxide.

[0020] In the present invention, the magnesium oxide has biodegradable properties and contains magnesium ions having a bone regeneration effect or an anti-inflammatory effect, and is not limited to the type thereof, but may be magnesium hydroxide (Mg(OH)2), magnesium carbonate (MgCO3), and magnesium oxide (MgO), and preferably magnesium oxide (MgO).

[0021] In addition, in the present invention, the manganese oxide is 'MnxOy 'As indicated by , it has the advantage of being able to mimic the function of SOD or CAT, and can act as a cofactor of various enzymes, including excellent antioxidant activity. In addition, it can generate manganese (Mn) ions that improve mitochondrial function as well as function as an enzyme, and the manganese oxide of the present invention is a material that is included in nano metal composite particles and plays a role in capturing active oxygen, and is not limited to the type thereof, but may include MnO2, Mn3O4, or Mn2O3.

[0022] In the present invention, the 'nano metal composite particle' is formed by synthesizing the magnesium oxide and manganese oxide, preferably magnesium oxide (MgO) and manganese oxide (MnxOy), and means, for example, a form in which magnesium oxide (MgO) is used as a core and manganese oxide (MnxOy) is synthesized on the surface of the magnesium oxide particle, preferably a form in which manganese oxide is synthesized on part or all of the surface of the magnesium oxide, and more preferably a form in which the magnesium oxide and manganese oxide are simultaneously exposed on the surface of the metal nano composite particle. The energy barrier was calculated to be relatively low in a form in which the magnesium oxide particle was partially exposed rather than completely covered by the manganese oxide.

[0023] Although not limited thereto, the nano metal composite particles of the present invention can be synthesized by mixing manganese oxide and magnesium oxide at a certain ratio, and the mixing ratio may be about 1:1 to 20, preferably 1:1 to 15, and more preferably 1:3 to 10, based on the weight ratio of manganese oxide and magnesium oxide.

[0024] Additionally, the nano-metal composite particles may further include a polymer coating. The polymer is included to mitigate the toxicity of manganese oxide and to enhance particle dispersibility. The polymer may include, but is not limited to, polymers such as chondroitin sulfate (CS), glucosamine sulfate, dopamine, chitosan, polyvinyl alcohol (PVA), or polyvinylpyrrolidone (PVP).

[0025] In another aspect of the present invention, the present invention relates to a nanozyme comprising nano metal composite particles comprising magnesium oxide and manganese oxide.

[0026] Nanozymes are substances that can act as biocatalysts in the body and replace enzymes, and in particular, they play a role in scavenging reactive oxygen species (ROS). The nano-metal composite particles produced in the present invention can scavenge reactive oxygen species in the body and simultaneously generate oxygen, thereby alleviating hypoxia conditions in specific organs, tissues, or cells in the body. Furthermore, they can secrete inflammatory cytokines through the effects of eliminating M1 macrophages and inducing anti-inflammatory M2 macrophages. Through these activities, the nanozymes of the present invention can be used as scavengers of reactive oxygen species and / or for the treatment of inflammatory diseases.

[0027] That is, as another aspect of the present invention, the present invention relates to a pharmaceutical composition for preventing or treating an inflammatory disease, comprising nano metal composite particles comprising magnesium oxide and manganese oxide.

[0028] The above “inflammatory disease” means a cytological or histological biological response caused by damage or abnormal stimulation by physical, chemical, biological action or substance, and is not limited to the types thereof, and may include, for example, rheumatoid arthritis, asthma, inflammatory bowel disease, autoimmune disease, Crohn’s disease, gout, asthma, atopy, inflammation after surgery or trauma, neuralgia, hepatitis, etc.

[0029] The term “prevention” in this specification means any action that can suppress or delay the onset of an inflammatory disease by administering the pharmaceutical composition according to the present invention.

[0030] The term “treatment” as used herein refers to any action that improves or benefits symptoms associated with an inflammatory disease by administering the pharmaceutical composition according to the present invention.

[0031] The pharmaceutical composition of the present invention can be formulated and used in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., external preparations, suppositories, and sterile injection solutions according to conventional methods, and may additionally include carriers or excipients necessary for the formulation. Pharmaceutically acceptable carriers, excipients, and diluents that may be additionally included in the active ingredient include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, magnesium stearate, and mineral oil. When formulating, it is usually prepared using diluents or excipients such as fillers, bulking agents, binders, wetting agents, disintegrants, and surfactants.

[0032] For example, solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations are prepared by mixing the extract or compound with at least one excipient, such as cotton, starch, calcium carbonate, sucrose or lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, oral solutions, emulsions, syrups, etc., and in addition to commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included.

[0033] Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solutions and suspensions can include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Suppository bases include witepsol, macrogol, Tween 61, cacao butter, laurin, and glycerogelatin.

[0034] The pharmaceutical composition of the present invention can be administered orally or parenterally (intravenously, subcutaneously, intraperitoneally, or topically) depending on the intended method, and the dosage varies depending on the patient's condition and weight, the degree of the disease, the drug form, the route of administration, and the time of administration, and can be selected in an appropriate form by a person skilled in the art.

[0035] The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. In the present invention, the term "pharmaceutically effective amount" means a reasonable amount applicable to medical treatment and an amount sufficient to treat a disease, and the standard thereof may be determined according to the patient's disease, severity, drug activity, drug sensitivity, administration time, administration route and excretion rate, treatment period, concomitantly used ingredients, and other factors. The pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or in combination with another therapeutic agent, and may be administered sequentially or simultaneously with conventional therapeutic agents. The dosage may be determined at a level that can minimize side effects by taking all of the above factors into consideration, and this can be easily determined by a person skilled in the art. Specifically, the dosage of the pharmaceutical composition may vary depending on the patient's age, weight, severity, sex, etc., and generally, 0.001 to 150 mg per 1 kg of body weight, more preferably 0.01 to 100 mg, may be administered once to three times a day, daily or every other day. However, this is an example and the dosage may be set differently as needed.

[0036] As another aspect of the present invention, the present invention relates to a method for producing nano metal composite particles comprising the magnesium oxide and manganese oxide.

[0037] In one embodiment, the nano metal composite particles of the present invention are manufactured according to the following steps.

[0038] 1) a step of modifying the surface by introducing an amine group onto the surface of magnesium oxide; and

[0039] 2) A step of synthesizing nano metal composite particles by mixing a manganese compound into magnesium oxide whose surface is modified with the above amine group.

[0040]

[0041] In one embodiment of the present invention, in order to bind manganese oxide to the surface of the magnesium oxide, a step of modifying the surface by introducing an amine group to the surface of the magnesium oxide is included. The above amine group can be introduced by treating magnesium oxide with an amine precursor, and the amine precursor is not limited to the type of primary or secondary amine, but may include polyethylenimine, tetraethylenepentamine, (2-Methylbutyl)amine, Tris(2-ethylhexyl)amine, ethyl amine, hydrazine, (3-Methylpentyl)amine, melamine, ethylenediamine, 3,5-diamino-1,2,4-triazole, adenine, 2-amino-1,4-benzenedicarboxylic acid, Isopropanolamine, 3-aminopropyltriethoxysilane (APTES), ethylenediamine, triethylenepentamine, aziridine, 5-amino-tetrazole, triethylenetetramine, monoethanolamine, 5-(4-carboxybenzoylamino)-isophthalic acid, N,N'aminopropyltriethoxysilane, N-(2-aminoethyl-)-3-aminopropylmethyldimethoxysilane,It may be at least one material selected from the group consisting of poly-(L-lysine), dodecylamine, tri-(2-aminoethyl)-amine, 3-(trimethoxysilylpropyl)diethylenetriamine, and L-arginine. In one embodiment of the present invention, among the materials, 3-aminopropyltriethoxysilane (APTES) was treated on magnesium oxide to produce MgO-NH2 having an amine group introduced on the surface of magnesium oxide.

[0042] Next, manganese oxide was added to the magnesium oxide having the above-described amine group and mixed, and then manganese oxide was synthesized through the above-described amine group. The manganese oxide (MnxOy) was synthesized by adding a solution containing manganese ions, which serve as a manganese source, and the solution is one that dissolves to generate Mn2 ions and has a form of a salt that can be easily reduced due to a low reduction potential. The solution is not limited to a type, but solutions such as potassium permanganate (KMnO4), Mn(NO3)2, MnCl2*?*4H2O, MnSO4*?*H2O, MnF2, and MnBr2 can be used. In one embodiment of the present invention, a potassium permanganate (KMnO4) solution was mixed with the magnesium oxide to form MgO@Mn, which is a combination of magnesium oxide and manganese oxide. x O y (X, Y are integers) composite particles were synthesized. The potassium permanganate (KMnO4) was reduced by the amine group of the MgO-NH2 to form MgO@Mn x O y Form composite particles.

[0043] In addition, in the present invention, MgO@Mn x O yThe mixing ratio of manganese oxide and magnesium oxide for forming particles may be about 1:1 to 20, preferably 1:1 to 15, and more preferably 1:3 to 10 to form MgO@Mn x O y Particles can be synthesized. MgO@Mn can be synthesized by changing the mixing ratio as above. x O y When producing particles, manganese oxide (Mn) is added to the surface of magnesium oxide. x O y ) are combined, there is a difference in the coverage ratio covering the surface. This difference in coverage affects the active oxygen capture effect of manganese oxide. That is, the greater the amount of manganese ions surrounding the magnesium oxide particles, the better the capture effect of active oxygen. However, it was confirmed that when too many manganese ions are included, the reduction capacity for capturing active oxygen becomes smaller, and when mixed in an appropriate ratio, the capture ability of active oxygen is maximized.

[0044] The nano-metal composite particles of the present invention may further include a step of adding a polymer coating. The polymer serves to alleviate toxicity and increase the dispersibility of the particles, and is not limited to a type thereof, but may include at least one polymer selected from the group consisting of chondroitin sulfate (CS), glucosamine sulfate, dopamine, chitosan, PVA, and PVP.

[0045] The present invention relates to a nano-metal composite particle comprising magnesium oxide and manganese oxide, and to a use as a nanozyme utilizing the active oxygen scavenging ability of the composite particle, and a method for producing the same. The nano-metal composite particle has excellent active oxygen scavenging ability due to manganese and is non-toxic due to the biodegradation activity of magnesium, and can be used as a nanozyme that can replace a biocatalyst and for various pharmaceutical purposes utilizing anti-inflammatory activity.

[0046]

[0047] Figure 1 is an image representation of the nano metal composite particles of the present invention.

[0048] Figure 2 schematically illustrates the process of inducing the effect of nano metal composite particles of the present invention on capturing active oxygen and promoting secretion of inflammatory cytokines.

[0049] Figure 3A is a diagram illustrating a process for producing nano metal composite particles of the present invention.

[0050] Figure 3B shows the results of measuring the zeta potential of each of the magnesium oxide and manganese oxide included in the production of the nano metal composite particles of the present invention, and the produced composite particles.

[0051] Figure 4A illustrates a process of producing MgO-NH2 by adding APTES to magnesium oxide to introduce an amine group to the surface of magnesium oxide for producing nano metal composite particles of the present invention.

[0052] Figure 4B shows the results of confirming whether an amine group was introduced to the surface of magnesium oxide through XRD peaks.

[0053] Figure 4C shows the results of confirming the modification of the magnesium oxide surface to include amine groups by the change in intensity of the magnesium oxide cubic peak using FT-IR peaks.

[0054] Figure 5A shows MgO@Mn by adding KMnO4, which is a source of manganese, to the synthesized MgO-NH2. x O y This shows the process of synthesizing particles.

[0055] Figure 5B is a result of confirming the process of combining KMnO4 to MgO-NH2 through XRD peaks. As a result of measuring the peaks of each material as a result of mixing KMnO4 and MgO-NH2, it was confirmed that the amine peak disappeared in XRD and the peaks of MnO2 and Mn3O4 existed simultaneously.

[0056] Figure 5C is MgO@Mn x O y When producing particles, the mixing ratios of KMnO4 and MgO-NH2 are adjusted to 1:3, 1:5, and 1:10, respectively, and mixed, and as a result, MgO@Mn produced from the mixture mixed at each ratio x O y This is the result of checking the FT-IR peaks for each ratio.

[0057] Figure 6 shows MgO@Mn produced by mixing KMnO4 and MgO-NH2 in the mixing ratios of 1:3, 1:5, and 1:10, respectively, in the present invention. x O y This is a TEM image of the particle.

[0058] Figure 7 shows MgO@Mn produced by mixing KMnO4 and MgO-NH2 in the mixing ratios of 1:3, 1:5, and 1:10, respectively, in the present invention. x O y This is the result of measuring and comparing the coverage of manganese oxide in particles.

[0059] Figure 8A shows the reactive oxygen species (ROS) scavenging mechanism of the nano metal composite particles of the present invention, and Figure 8B shows the scavenging effect thereof, with respect to the H2O2 scavenging rate and SOD activity measured at different mixing ratios of KMnO4 and MgO-NH2.

[0060] FIG. 9A is a result of measuring cyclic voltammetry at different mixing ratios of KMnO4 and MgO-NH2 to confirm the ROS scavenging effect of the nano metal composite particles of the present invention, and FIG. 9B is a result of comparing the ROS scavenging ability through the closed curve area of ​​the cyclic voltammetry.

[0061] Figure 10 shows the energy barrier calculated to confirm the reactive oxygen species (ROS) scavenging effect of the nano metal composite particles of the present invention, and the composite particles (MgO@Mn) with magnesium oxide or manganese oxide particles x O y ) is the result of comparing the energy barrier and the active oxygen capture ability.

[0062] In one aspect, the present invention relates to nano metal composite particles comprising magnesium oxide and manganese oxide.

[0063] The magnesium oxide may be selected from magnesium hydroxide (Mg(OH)2), magnesium carbonate (MgCO3) or magnesium oxide (MgO), and the manganese oxide may be selected from MnO2, Mn3O4 or Mn2O3.

[0064] The above nano metal composite particles may be in a form in which manganese oxide is synthesized and bonded to all or part of the surface of magnesium oxide, and the magnesium oxide and manganese oxide of the nano metal composite particles may be simultaneously exposed on the surface.

[0065] Additionally, the magnesium oxide may have a surface modified with an amine group.

[0066] Additionally, the nano metal composite particles may contain manganese oxide and magnesium oxide in a weight ratio of 1:1 to 20.

[0067] The nano metal composite particles of the present invention may additionally include a polymer coating.

[0068] The above nano metal composite particles have a capturing effect of reactive oxygen species (ROS).

[0069] In another aspect of the present invention, the present invention relates to a nanozyme comprising the above nano metal composite particles.

[0070] In another aspect of the present invention, the present invention relates to a pharmaceutical composition for preventing or treating an inflammatory disease, comprising the nano metal composite particles described above.

[0071] In another aspect of the present invention, the present invention relates to the use of the nano metal composite particles of claim 1 for the manufacture of a drug for treating an inflammatory disease.

[0072] In another aspect of the present invention, the present invention relates to a method for preventing or treating an inflammatory disease, comprising administering a pharmaceutical composition comprising the nano metal composite particles to a patient suffering from the inflammatory disease.

[0073] In another aspect of the present invention, the present invention relates to a method for producing nano metal composite particles comprising the following steps.

[0074] 1) a step of modifying the surface to introduce an amine group onto the surface of magnesium oxide; and

[0075] 2) A step of mixing manganese oxide into the magnesium oxide whose surface is modified with the above amine group.

[0076]

[0077] Hereinafter, examples will be described in detail to specifically explain this specification. However, the embodiments according to this specification may be modified in various different forms, and the scope of this specification is not limited to the embodiments described below. The embodiments of this specification are provided to more fully explain this specification to those of average skill in the art.

[0078]

[0079] Example 1. Nano metal composite particles (MgO@Mn x O y ) manufacturing

[0080] Nano metal composite particles (MgO@Mn) of the present invention x O y ) is illustrated in Fig. 3A.

[0081] 1-1. Introduction of amine groups to the surface of magnesium oxide_MgO-NH2 generation

[0082] First, in order to introduce amine groups onto the MgO surface, 10 ml of distilled water was added to 100 mg of MgO and stirred at room temperature for 30 minutes. 0.2 ml of APTES ((3-Aminopropyl)triethoxysilane) was added and reacted at 65°C for 24 hours (Fig. 4A). After the reaction was completed, MgO-NH2 with amine groups introduced onto the surface of the magnesium oxide was generated, and the peaks of each material were confirmed using X-ray diffraction (XRD) and FT-IR spectroscopy to confirm the surface modification by the amine groups.

[0083] As a result, as confirmed in Fig. 4B, in the XRD peak graph, it was confirmed that the magnesium oxide (MgO) peak disappeared and the amine peak appeared as the amine group of APTES attached to the surface of magnesium oxide. In addition, since the reaction proceeded in DW, the peak of Mg(OH)2 was also observed.

[0084] In addition, as confirmed in Fig. 4C, the analysis results by FT-IR spectroscopy confirmed that the peak of the MgO cube was lowered and an amine peak appeared.

[0085] From the above results, it was confirmed whether an amine group was introduced to the surface of magnesium oxide.

[0086] 1-2. Synthesis of MgO@MnxOy particles

[0087] MgO@Mn is obtained by adding potassium permanganate (KMnO4) solution, which is a manganese source, to the MgO-NH2 synthesized in the above 1-1. x O y Particles were synthesized. First, 10 mg of potassium permanganate (KMnO4) solution was mixed in 20 ml of distilled water (DW), and 30 mg of MgO-NH2 synthesized in 1-1 and 10 mg of urea were mixed and stirred at room temperature for 10 minutes. Afterwards, the mixture was reacted at 170°C for 24 hours to obtain MgO@Mn x O y The particles were synthesized (Fig. 5A).

[0088] At this time, the mixing ratios of the potassium permanganate (KMnO4) solution and MgO-NH2 were 1:3, 1:5 and 1:10, respectively, to form MgO@Mn x O y Particles were synthesized (MM1:3, MM1:5, MM1:10) and the characteristics of each particle were confirmed using X-ray diffraction analysis (XRD) and FT-IR spectroscopy for the particles generated at each mixing ratio.

[0089] Figure 5B is the XRD analysis result, confirming that the amine peak disappeared and the MnO2 and Mn3O4 peaks existed simultaneously, and Figure 5C is the analysis result by FT-IR spectroscopy, confirming that the amine peak disappeared and the MnO2 and Mn3O4 peaks existed simultaneously. -1 It was confirmed that a Mn-O bond was formed nearby.

[0090] In addition, the particles synthesized as above were observed through TEM. As shown in Fig. 6, the part covered with magnesium oxide is shown in red, and the part covered with manganese oxide is shown in green. In the case of MM 1:10, which contains the lowest ratio of potassium permanganate solution, most of the magnesium oxide (MgO) appears to be uncovered and exposed, and in the case of MM 1:5, manganese oxide (Mn x O y) and magnesium oxide (MgO) were observed to be partially present. In the case of MM 1:3, which contained the highest proportion of potassium permanganate solution, it was confirmed that the surface of the particles was almost entirely covered with manganese. The surface coverage ratio observed from the above TEM images was quantified and compared in Fig. 7.

[0091] Example 2. Nano metal composite particles (MgO@Mn x O y ) active oxygen scavenging effect

[0092] 2-1. Measurement of hydrogen peroxide capture capacity and SOD activity

[0093] Manganese oxide has a catalytic effect on its own, so it can decompose hydrogen peroxide (H2O2), and thus react directly with it and capture it.

[0094] Also, when manganese oxide is used as a reactant, it is ionized and its ions act as collectors again. That is, Mn 2+ Ions are O2 radicals, Mn 4+ The ions capture hydrogen peroxide, and Mn 3+ Ions can activate MnSOD, which captures O2 radicals, thereby capturing reactive oxygen species (ROS).

[0095] Therefore, an experiment was conducted to compare the capture ability according to the amount of manganese oxide, and the capture effect of each particle according to the concentration of manganese was compared using the metal composite particles produced in Example 1.

[0096] As a result, as shown in Fig. 8B, it was confirmed that the capture effect was the best in the case of MM 1:5, where manganese oxide partially covers the particle surface, rather than in the case of MM1:3, where the amount of manganese oxide was the largest. This result is thought to be because manganese in the cell interacts with proteins and ATP to activate MnSOD and capture superoxide radicals. O2 radicals generated during ATP production in mitochondria cannot pass through the mitochondrial membrane, but hydrogen peroxide generated through MnSOD easily passes through the membrane. In other words, Mn 4+ The ions capture hydrogen peroxide and form O2, Mn 2+ Create and Mn 2+ The ions react again with O2 radicals, mimicking the activity of SOD. This mechanism is what appears.

[0097] 2-2. Cyclic Voltammetry (CV) Analysis

[0098] To determine the difference in capture activity according to the amount of manganese oxide compared to the amount of magnesium oxide, the potential difference according to the oxidation / reduction reaction was measured using cyclic voltammetry. In Figure 9A, the peak in the upper right represents the oxidation reaction peak, and the peak in the lower left represents the reduction reaction peak. The measured graph confirms that the reduction peak is stronger than the oxidation peak, indicating that the oxidation-reduction reaction is not reversible, but rather an irreversible reaction in which only the reduction reaction occurs.

[0099] In addition, the capture effect can be confirmed by calculating the area of ​​the closed curve of the above graph, and the larger the area, the greater the reduction capacity, indicating a superior ability to capture active oxygen. Therefore, as a result of calculating the area of ​​each of these graphs, it was calculated that the area was the largest when MM 1:5, which can be seen that the particles of MM 1:5 have a greater reduction capacity than other particles, and thus a greater ability to capture active oxygen.

[0100] 2-3. Energy barrier calculation

[0101] The lower the measured energy barrier value, the better it reacts with hydrogen peroxide and the better its ability to capture reactive oxygen species. First, the energy barrier for each single particle of magnesium oxide or manganese oxide (MnO2) was compared with the energy barrier when magnesium is bonded to MgO@MnO2 and the magnesium ions are decomposed and adsorbed on the surface of manganese oxide. As a result of calculating using a computer simulation technique, it was confirmed that the structure in which magnesium is bonded to MgO@MnO2 has the lowest energy barrier, which can explain its highest capture ability.

[0102]

[0103] The present invention has been described above, focusing on preferred embodiments thereof. Those skilled in the art will appreciate that the present invention can be implemented in modified forms without departing from its essential characteristics. Therefore, the disclosed embodiments should be considered illustrative rather than restrictive. The scope of the present invention is set forth in the claims, not the foregoing description, and all differences within the scope equivalent thereto should be construed as being encompassed by the present invention.

Claims

1. Nano metal composite particles containing magnesium oxide and manganese oxide.

2. In paragraph 1, Nano metal composite particles, wherein the magnesium oxide is selected from the group consisting of magnesium hydroxide (Mg(OH)2), magnesium carbonate (MgCO3), and magnesium oxide (MgO).

3. In paragraph 1, Nano metal composite particles, wherein the manganese oxide is selected from the group consisting of MnO2, Mn3O4 and Mn2O3.

4. In paragraph 1, The above nano metal composite particle is a nano metal composite particle that includes a form in which manganese oxide is synthesized and bonded to all or part of the surface of magnesium oxide.

5. In paragraph 4, Magnesium oxide and manganese oxide of the above nano metal composite particles are simultaneously exposed on the surface of the nano metal composite particles.

6. In paragraph 1, The above nano metal composite particles are nano metal composite particles containing manganese oxide and magnesium oxide in a weight ratio of 1:1 to 20.

7. In paragraph 4, The above magnesium oxide is a nano metal composite particle having a surface modified with an amine group.

8. In paragraph 1, A nano metal composite particle, wherein the nano metal composite particle further comprises a polymer coating.

9. In paragraph 1, The above nano metal composite particles are nano metal composite particles having a capture effect of reactive oxygen species (ROS).

10. A nanozyme comprising the nano metal composite particle of paragraph 1.

11. A pharmaceutical composition for preventing or treating inflammatory diseases, comprising the nano metal composite particles of paragraph 1.

12. Use of the nano metal composite particles of claim 1 for the manufacture of a drug for the treatment of inflammatory diseases.

13. A method for preventing or treating an inflammatory disease, comprising administering a pharmaceutical composition comprising the nano metal composite particles of paragraph 1 to a patient suffering from an inflammatory disease. 14.1) A step of modifying the surface to introduce an amine group onto the surface of magnesium oxide; and 2) A method for producing nano metal composite particles of claim 1, comprising a step of mixing manganese oxide into magnesium oxide whose surface is modified with the above amine group.

15. In paragraph 14, A method for producing nano metal composite particles, characterized in that the manganese oxide and magnesium oxide are included in a ratio of 1:1 to 20.

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