Preparation method of biocompatible spheroid-like nanometer trimanganese tetraoxide and product thereof

Abstract

The application discloses a kind of preparation methods and products of biological friendly spheroid-like trimanganese tetraoxide nanometer, it is related to functional nanometer material technical field;The application includes that manganese salt is mixed with ultrapure water and obtains manganese salt solution;Catalyst, modifier are added and stirred uniformly, catalyst is selected from monoethanolamine, diethanolamine, triethanolamine, modifier is selected from polyethylene glycol, sodium alginate and its derivative, chitosan and its derivative, water-soluble cellulose and its derivative;Basic solution and acidic solution are added dropwise to adjust the pH value of manganese salt solution, ultrapure water is added and stirred uniformly and poured into hydrothermal reaction kettle;Hydrothermal reaction kettle is placed in drying oven and heated to complete reaction to obtain trimanganese tetraoxide slurry;Filter, rinse and dry to obtain trimanganese tetraoxide powder product;The application effectively reduces the biological toxicity of trimanganese tetraoxide nanoparticle, meets the strict biomedical application requirement, preparation method is simple, process condition is mild, does not need expensive equipment, and cost is conducive to control.

Description

Technical Field

[0001] This invention relates to the field of functional nanomaterials technology, specifically to a method and product for preparing bio-friendly spherical manganese tetroxide nanoparticles. Background Technology

[0002] Manganese tetroxide (Mn3O4) is a metal oxide widely used in scientific research and production, especially in traditionally popular fields. It can be used as a raw material for manganese-zinc ferrites, an anode material for lithium-ion batteries, a catalyst for nitrogen oxides, and a material for gas sensors. Furthermore, manganese oxides and their derivatives are attracting attention in fields such as bioimaging, biosensing, gene delivery, and cancer therapy due to their stability, elemental abundance, and tunable structure.

[0003] Traditional natural enzymes suffer from limitations such as high price, low yield, low stability, and potential immunogenicity. Nanoenzymes offer a solution. Among numerous nanomaterials, manganese tetroxide nanoparticles stand out due to their unique Mn content. 2+ / Mn 3+ Its mixed oxidation state, high irreversible oxidation stability, and large specific surface area give it significant multi-enzyme-like activity, enabling it to quench reactive oxygen species (ROS).

[0004] However, manganese tetroxide poses potential toxicity risks in vivo, making it difficult to meet stringent biomedical requirements. In biological environments, it may release manganese ions (Mn2) through dissolution or metabolism. 2+ Manganese ions are an essential trace element at low concentrations, but at higher concentrations they can be toxic to the nervous system and other organs, leading to cellular oxidative stress, DNA damage, and inflammatory responses. Therefore, there is an urgent need for a bio-friendly method and product for preparing near-spherical nano-manganese tetroxide to address this problem. Summary of the Invention

[0005] The purpose of this invention is to provide a method and product for preparing bio-friendly spherical nano-manganese tetroxide, in order to solve the problems mentioned in the background art.

[0006] To achieve the above objectives, the present invention provides the following technical solution: a method for preparing bio-friendly spherical nano-manganese tetroxide, comprising the following specific steps:

[0007] S1 mixes manganese salt with ultrapure water to obtain a manganese salt solution;

[0008] S2. Add an appropriate amount of catalyst and modifier to the manganese salt solution and stir evenly. The catalyst is one or more of monoethanolamine, diethanolamine, and triethanolamine, and the modifier is one or more of polyethylene glycol, sodium alginate and its derivatives, chitosan and its derivatives, and water-soluble cellulose and its derivatives.

[0009] S3 is used to prepare an alkaline solution of a certain concentration;

[0010] S4 is used to prepare an acidic solution of a certain concentration;

[0011] S5 is adjusted by adding alkaline and acidic solutions to adjust the pH of the manganese salt solution, and an appropriate amount of ultrapure water is added. After stirring evenly, the solution is poured into the hydrothermal reactor.

[0012] S6 Place the hydrothermal reactor into the drying oven, set a certain heating and heat preservation curve, and obtain manganese tetroxide slurry after the reaction is complete;

[0013] S7 filters, rinses, and dries the manganese tetroxide slurry to obtain manganese tetroxide powder.

[0014] Preferably, in step S1 above, the manganese salt is one or more of manganese chloride, manganese acetate, and manganese gluconate, and the concentration of manganese ions in the manganese salt solution is 0.5 to 1 mol / L.

[0015] Preferably, in step S2 above, the amount of catalyst added is 1 to 10% of the mass of manganese ions, and the amount of modifier added is 5 to 15% of the mass of manganese ions.

[0016] Preferably, the alkaline solution in step S3 is one or more of sodium hydroxide solution, potassium hydroxide solution, and ammonia solution, and the concentration of the alkaline solution is 1 to 6 mol / L; the acidic solution in step S4 is one or more of phosphoric acid, formic acid, acetic acid, and citric acid, and the concentration of the acidic solution is 1 to 6 mol / L.

[0017] Preferably, in step S5 above, the pH value of the manganese salt solution is adjusted to 4-6.

[0018] Preferably, in step S5 above, after adding ultrapure water, the concentration of manganese ions in the solution is 0.25-0.5 mol / L, and the solution volume is 20-50% of the total volume of the hydrothermal reactor liner.

[0019] Preferably, in step S6 above, the heating and holding curve is as follows: the temperature is raised to 150°C at a rate of 1-5°C / min, and then held for 8-10 hours.

[0020] Preferably, in step S7 above, rinsing refers to repeatedly washing with ultrapure water 3 times or more to remove other free ions from the object to be washed; the drying temperature is 60-80℃ and the drying time is 8-16 hours.

[0021] Another technical solution provided by the present invention is a bio-friendly spherical nano-manganese tetroxide product prepared by the above preparation method, which, when added to the environmental system in which biological cells exist, does not inhibit the growth of biological cells or reduce the survival rate of biological cells.

[0022] Preferably, in the above-mentioned manganese tetroxide product, the Pb impurity content is less than 500 ppb, the Cd impurity content is less than 500 ppb, the Sn impurity content is less than 50 ppm, the Ni impurity content is less than 1 ppm, the Cr impurity content is less than 1 ppm, the Cu impurity content is less than 10 ppm, the particle size D50 of the manganese tetroxide product is 50-500 nm, and the specific surface area is 10-20 m². 2 / g.

[0023] Compared with the prior art, the beneficial effects of the present invention are:

[0024] 1. This method and product for preparing bio-friendly spherical manganese tetroxide nanoparticles effectively reduces the biotoxicity of manganese tetroxide nanoparticles by introducing polyethylene glycol, sodium alginate and its derivatives, chitosan and its derivatives, and / or water-soluble cellulose and its derivatives as modifiers during the preparation process. The modified product can significantly reduce Mn. 2+ The release of manganese ions reduces the risk of toxicity such as cellular oxidative stress, DNA damage, and inflammatory responses caused by manganese ions, thus meeting the stringent requirements for biomedical applications.

[0025] 2. The preparation method and product of this bio-friendly spherical nano-manganese tetroxide can reduce the introduction of heavy metal elements by controlling the content of heavy metal elements in the main raw materials, thereby further controlling the product toxicity.

[0026] 3. The preparation method and product of this bio-friendly spherical nano-manganese tetroxide, through precise control of reactant concentration and pH value and optimization of preparation conditions, makes the obtained manganese tetroxide nanoparticles more uniform in morphology and concentrated in particle size distribution. The repeatability and stability of the product are improved, making it suitable for mass production and application.

[0027] 4. The preparation method of this bio-friendly spherical nano-manganese tetroxide is simple, using ultrapure water as a solvent and employing non-toxic modifiers, which reduces the burden on the environment. In addition, the raw materials and process conditions used in this method are relatively mild, requiring no expensive equipment or extreme conditions, which further reduces energy consumption and costs. Attached Figure Description

[0028] Figure 1 SEM image of manganese tetroxide prepared in Example 1;

[0029] Figure 2 The XRD pattern of manganese tetroxide prepared in Example 1;

[0030] Figure 3 The changes in OD values ​​over time in the petri dish of Example 1 under different concentration treatments are shown. Detailed Implementation

[0031] To address the potential toxicity risks of manganese tetroxide in vivo, this invention proposes a new feasible solution for preparing bio-friendly spherical nano-manganese tetroxide, specifically:

[0032] S1 mixes manganese salt with ultrapure water to obtain a manganese salt solution;

[0033] Optionally, the manganese salt can be manganese chloride (MnCl2), manganese acetate (generally in hydrate form Mn(CH3COO)2·4H2O), or manganese gluconate (Mn(C6H2O)2·4H2O). 11 One or more of O7)2), and optionally, the concentration of manganese ions in the manganese salt solution should be controlled at 0.5 to 1 mol / L;

[0034] S2. Add an appropriate amount of catalyst and modifier to the manganese salt solution and stir evenly. The catalyst is one or more of monoethanolamine, diethanolamine, and triethanolamine, and the modifier is one or more of polyethylene glycol (e.g., PEG3000, PEG6000, etc.), sodium alginate and its derivatives, chitosan and its derivatives, and water-soluble cellulose and its derivatives.

[0035] For reference, the amount of catalyst added can be 1 to 10% of the mass of manganese ions, and the amount of modifier added can be 5 to 15% of the mass of manganese ions.

[0036] S3 is used to prepare an alkaline solution of a certain concentration;

[0037] Optionally, the alkaline solution is one or more of sodium hydroxide solution, potassium hydroxide solution, and ammonia solution, and the concentration of the alkaline solution is 1 to 6 mol / L;

[0038] S4 is used to prepare an acidic solution of a certain concentration;

[0039] Optionally, the acidic solution is one or more of phosphoric acid, formic acid, acetic acid, and citric acid, and the concentration of the acidic solution is 1 to 6 mol / L;

[0040] The order of steps S3 and S4 above can be adjusted arbitrarily, and reagents can be prepared in advance or purchased existing reagents can be used.

[0041] S5 is adjusted by adding alkaline and acidic solutions to adjust the pH of the manganese salt solution, and an appropriate amount of ultrapure water is added. After stirring evenly, the solution is poured into the hydrothermal reactor.

[0042] In a preferred embodiment, the pH of the manganese salt solution is adjusted to 4-6;

[0043] Alternatively, the concentration of manganese ions in the solution after adding ultrapure water can be 0.25–0.5 mol / L, and the solution volume can be 20–50% of the total volume of the hydrothermal reactor liner.

[0044] S6 Place the hydrothermal reactor into the drying oven, set a certain heating and heat preservation curve, and obtain manganese tetroxide slurry after the reaction is complete;

[0045] For reference, the heating and holding curve can be at a rate of 1 to 5°C / min, specifically heated to 150°C and then held for 8 to 10 hours.

[0046] S7 filters, rinses, and dries the manganese tetroxide slurry to obtain manganese tetroxide powder.

[0047] The rinsing process can be repeated three or more times with ultrapure water to remove other free ions from the items to be washed; the drying temperature should be 60-80℃ and the drying time should be 8-16 hours.

[0048] Experiments have verified that the product prepared by the method of this invention, when added to the environmental system in which biological cells exist, will not inhibit the growth of biological cells or reduce the survival rate of biological cells.

[0049] To further improve the safety of the above products, impurity content can be controlled from the raw material end, resulting in high-purity manganese tetroxide products with the following impurity content: Pb less than 500 ppb, Cd less than 500 ppb, Sn less than 50 ppm, Ni less than 1 ppm, Cr less than 1 ppm, and Cu less than 10 ppm. Specifically, this can be achieved by controlling the raw material end, i.e., ensuring that the impurity content of Pb, Cd, Sn, Ni, Cr, and Cu in the manganese salt is less than 500 ppb, 500 ppb, 500 ppm, 1 ppm, 1 ppm, and 10 ppm, respectively. In actual production, appropriate manganese salts can be selected according to production requirements. For example, if the impurity content of Pb, Cd, Sn, Ni, Cr, and Cu is less than 10 ppm, the impurity content of the manganese tetroxide product will also fall within this range.

[0050] Furthermore, in a preferred embodiment, the particle size of the manganese tetroxide product obtained by the present invention can be controlled to be less than 1 μm with a D50 and a specific surface area of ​​10–50 m². 2 / g, and even better, the particle size can be controlled within a D50 of 50–500 nm and a specific surface area of ​​10–20 m² / g. 2 / g.

[0051] To enable those skilled in the art to understand the present invention, the present invention will be described in detail below with reference to the accompanying drawings and specific embodiments, but the scope of protection of the present invention is not limited to the following specific embodiments.

[0052] Example 1:

[0053] (1) 6.127g of manganese acetate (Mn(CH3COO)2·4H2O) was mixed with 50ml of ultrapure water to obtain a manganese salt solution;

[0054] (2) Add 0.07g of triethanolamine and 0.11g of polyethylene glycol (PEG3000) to the manganese acetate solution in step (1) above, and stir until homogeneous.

[0055] (3) Prepare a 6 mol / L sodium hydroxide solution.

[0056] (4) Prepare a 6 mol / L acetic acid solution;

[0057] (5) Adjust the pH of the solution in step (2) to 5 by adding the acid and base solutions from steps (3) and (4) above, and add ultrapure water to 100ml, stir evenly and add to 200ml hydrothermal reactor;

[0058] (6) Add the hydrothermal reactor of step (5) above into the drying oven, set the heating rate to 2℃ / min, heat to 150℃ and keep it at 8h until the reaction is complete to obtain manganese tetroxide slurry.

[0059] (7) After filtering the manganese tetroxide slurry after step (6), rinse it three times with ultrapure water and dry it at 70°C for 10 hours to obtain manganese tetroxide powder product.

[0060] The SEM and XRD patterns of the manganese tetroxide product prepared in Example 1 are shown in the figures below. Figure 1 and Figure 2 .

[0061] Cytotoxicity assay: at 4 × 10 5 L929 cells were seeded at a density of / mL in culture dishes. After cell adhesion, different concentrations of pulverized, bio-friendly spherical manganese tetroxide nanoparticles (Example 1) were added, and the dishes were incubated at 37℃ and 5% CO2. Cell viability was measured using a cell counting kit (CCK8) on days 1, 3, and 7. The changes in OD values ​​over time (day 1, day 3, and day 7) under different concentrations (PBS, 0.2, 0.5, 0.8, 1, 2 mg / mL) are shown in the table. Figure 3The vertical axis represents the cell survival rate results. The concentration of bio-friendly spherical nano-manganese tetroxide gradually increases in each group of data according to the direction of the arrow. As can be seen from the figure, the bio-friendly spherical nano-manganese tetroxide has no obvious cytotoxicity. It did not inhibit the growth of biological cells, and the survival rate of biological cells remained basically at the same level, with no impact observed.

[0062] Example 2:

[0063] (1) 3.677 g of manganese acetate (Mn(CH3COO)2·4H2O) was mixed with 30 ml of ultrapure water to obtain a manganese salt solution;

[0064] (2) Add 0.04g of triethanolamine and 0.066g of polyethylene glycol (PEG3000) to the manganese acetate solution in step (1) above, and stir until homogeneous.

[0065] (3) Prepare a 6 mol / L sodium hydroxide solution.

[0066] (4) Prepare a 6 mol / L acetic acid solution;

[0067] (5) Adjust the pH of the solution in step (2) to 5 by adding the acid and base solutions from steps (3) and (4) above, and add ultrapure water to 60 ml, stir evenly and add to 200 ml hydrothermal reactor;

[0068] (6) Add the hydrothermal reactor of step (5) above into the drying oven, set the heating rate to 5℃ / min, heat to 150℃ and keep it at 10h until the reaction is complete to obtain manganese tetroxide slurry.

[0069] (7) After filtering the manganese tetroxide slurry after step (6), rinse it three times with ultrapure water and dry it at 70°C for 10 hours to obtain manganese tetroxide powder product.

[0070] Example 3:

[0071] (1) 3.677 g of manganese acetate (Mn(CH3COO)2·4H2O) was mixed with 30 ml of ultrapure water to obtain a manganese salt solution;

[0072] (2) Add 0.04g of triethanolamine and 0.066g of polyethylene glycol (PEG3000) to the manganese acetate solution in step (1) above, and stir until homogeneous.

[0073] (3) Prepare a 6 mol / L sodium hydroxide solution.

[0074] (4) Prepare a 6 mol / L acetic acid solution;

[0075] (5) Adjust the pH of the solution in step (2) to 5 by adding the acid and base solutions from steps (3) and (4) above, and add ultrapure water to 60 ml, stir evenly and add to 200 ml hydrothermal reactor;

[0076] (6) Add the hydrothermal reactor of step (5) above into the drying oven, set the heating rate to 2℃ / min, heat to 150℃ and keep it at 8h until the reaction is complete to obtain manganese tetroxide slurry.

[0077] (7) After filtering the manganese tetroxide slurry after step (6), rinse it three times with ultrapure water and dry it at 70°C for 10 hours to obtain manganese tetroxide powder product.

[0078] Example 4:

[0079] (1) 3.677 g of manganese acetate (Mn(CH3COO)2·4H2O) was mixed with 30 ml of ultrapure water to obtain a manganese salt solution;

[0080] (2) Add 0.04g of triethanolamine and 0.066g of sodium alginate to the manganese acetate solution in step (1) above, and stir until homogeneous.

[0081] (3) Prepare a 6 mol / L sodium hydroxide solution.

[0082] (4) Prepare a 6 mol / L acetic acid solution;

[0083] (5) Adjust the pH of the solution in step (2) to 5 by adding the acid and base solutions from steps (3) and (4) above, and add ultrapure water to 60 ml, stir evenly and add to 200 ml hydrothermal reactor;

[0084] (6) Add the hydrothermal reactor of step (5) above into the drying oven, set the heating rate to 2℃ / min, heat to 150℃ and keep it at 10h until the reaction is complete to obtain manganese tetroxide slurry.

[0085] (7) After filtering the manganese tetroxide slurry after step (6), rinse it three times with ultrapure water and dry it at 70°C for 10 hours to obtain manganese tetroxide powder product.

[0086] Example 5:

[0087] (1) 3.677 g of manganese acetate (Mn(CH3COO)2·4H2O) was mixed with 30 ml of ultrapure water to obtain a manganese salt solution;

[0088] (2) Add 0.04g of triethanolamine and 0.066g of chitosan to the manganese acetate solution in step (1) above, and stir until homogeneous.

[0089] (3) Prepare a 6 mol / L sodium hydroxide solution.

[0090] (4) Prepare a 6 mol / L acetic acid solution;

[0091] (5) Adjust the pH of the solution in step (2) to 5 by adding the acid and base solutions from steps (3) and (4) above, and add ultrapure water to 60 ml, stir evenly and add to 200 ml hydrothermal reactor;

[0092] (6) Add the hydrothermal reactor of step (5) above into the drying oven, set the heating rate to 2℃ / min, heat to 150℃ and keep it at 8h until the reaction is complete to obtain manganese tetroxide slurry.

[0093] (7) After filtering the manganese tetroxide slurry after step (6), rinse it three times with ultrapure water and dry it at 70°C for 10 hours to obtain manganese tetroxide powder product.

[0094] Example 6:

[0095] (1) 6.127g of manganese acetate (Mn(CH3COO)2·4H2O) was mixed with 50ml of ultrapure water to obtain a manganese salt solution;

[0096] (2) Add 0.07g of triethanolamine and 0.13g of sodium carboxymethyl cellulose (CMC-Na) to the manganese acetate solution in step (1) above, and stir until homogeneous.

[0097] (3) Prepare a 6 mol / L sodium hydroxide solution.

[0098] (4) Prepare a 6 mol / L acetic acid solution;

[0099] (5) Adjust the pH of the solution in step (2) to 5 by adding the acid and base solutions from steps (3) and (4) above, and add ultrapure water to 100ml, stir evenly and add to 200ml hydrothermal reactor;

[0100] (6) Add the hydrothermal reactor of step (5) above into the drying oven, set the heating rate to 2℃ / min, heat to 150℃ and keep it at 10h until the reaction is complete to obtain manganese tetroxide slurry.

[0101] (7) After filtering the manganese tetroxide slurry after step (6), rinse it three times with ultrapure water and dry it at 70°C for 10 hours to obtain manganese tetroxide powder product.

[0102] The physicochemical properties of the manganese tetroxide products obtained in Examples 1-6 were tested, and the results are shown in Table 1. The results show that the manganese tetroxide products prepared by the invented method have high purity, low heavy metal impurity content, and their physical properties meet the requirements.

[0103] Table 1. Physicochemical properties of manganese tetroxide products prepared in Examples 1 to 6

[0104]

[0105] The above are merely preferred embodiments of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope defined in the claims.

[0106] Any aspects of this invention not described in detail are well-known to those skilled in the art.

Claims

1. A method for preparing bio-friendly spherical nano-manganese tetroxide, characterized in that, The specific steps include the following: S1. Manganese salt is mixed with ultrapure water to obtain a manganese salt solution, and the concentration of manganese ions in the manganese salt solution is 0.5-1 mol / L; S2. Add appropriate amounts of catalyst and modifier to manganese salt solution. The amount of catalyst added is 1-10% of the mass of manganese ions, and the amount of modifier added is 5-15% of the mass of manganese ions. Stir evenly. The catalyst is one or more of monoethanolamine, diethanolamine, and triethanolamine, and the modifier is one or more of polyethylene glycol, sodium alginate and its derivatives, chitosan and its derivatives, and water-soluble cellulose and its derivatives. S3 is used to prepare an alkaline solution of a certain concentration; S4 is used to prepare an acidic solution of a certain concentration; S5 is prepared by adding alkaline and acidic solutions to adjust the pH of the manganese salt solution to 4-6, and then adding an appropriate amount of ultrapure water. After adding ultrapure water, the concentration of manganese ions in the solution is 0.25-0.5 mol / L, and the volume of the solution is 20-50% of the total volume of the hydrothermal reactor liner. The solution is stirred evenly and poured into the hydrothermal reactor. S6 Place the hydrothermal reactor into the drying oven, set the heating and holding curve to a rate of 1-5℃ / min, heat to 150℃ and hold for 8-10 hours, and obtain manganese tetroxide slurry after the reaction is complete. S7 filters, rinses, and dries the manganese tetroxide slurry to obtain manganese tetroxide powder.

2. The method for preparing a bio-friendly spherical nano-manganese tetroxide according to claim 1, characterized in that: In step S1, the manganese salt is one or more of manganese chloride, manganese acetate, and manganese gluconate.

3. The method for preparing a bio-friendly spherical nano-manganese tetroxide according to claim 1, characterized in that: The alkaline solution in step S3 is one or more of sodium hydroxide solution, potassium hydroxide solution, and ammonia solution, with a concentration of 1 to 6 mol / L; the acidic solution in step S4 is one or more of phosphoric acid solution, formic acid solution, acetic acid solution, and citric acid solution, with a concentration of 1 to 6 mol / L.

4. The method for preparing a bio-friendly spherical nano-manganese tetroxide according to claim 1, characterized in that: In step S7, rinsing refers to repeatedly washing with ultrapure water more than 3 times to remove other free ions from the items to be washed; the drying temperature is 60-80℃ and the drying time is 8-16 hours.

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