Purification method and purified product of inorganic nanoparticles modified with low- and medium-molecular weight polyethylene glycol derivatives

Abstract

The present invention relates to the technical field of the production of nanocomposites, and particularly to a purification method for inorganic nanoparticles modified with medium- and low-molecular-weight polyethylene glycol derivatives. The purification method for inorganic nanoparticles modified with medium- and low-molecular-weight polyethylene glycol derivatives provided by the present invention realizes high-purity purification through the combination and sequence of process steps including preparation of stock solution, alkane sedimentation, alkane washing, acid dissolution, extraction and phase separation with an ether solvent, and nanofiltration membrane separation. By purifying the inorganic nanoparticles modified with medium- and low-molecular-weight polyethylene glycol derivatives through the present invention, emulsification and aggregation of the inorganic nanoparticles in the nanofiltration membrane are effectively prevented, the use efficiency of the nanofiltration membrane equipment is improved, the corrosion of the nanofiltration membrane equipment by organic solvents is reduced, and at the same time, the obtained product has high purity, contains less free polyethylene glycol derivatives, has a concentrated hydrodynamic size distribution and good monodispersity, has high potential for industrial application, and can meet the requirements of large-scale production.

Description

Technical Field

[0001] The present invention relates to the technical field of the production of nanocomposites, and particularly to a purification method and a purified product of inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives. Background Art

[0002] The high-temperature thermal decomposition method is a mature and efficient method for synthesizing inorganic nanoparticles, and the synthesized nanoparticles have a low defect rate and excellent crystallinity. However, the nanoparticles synthesized by this method are usually coated with long-chain fatty acids or fatty amines such as oleic acid, oleylamine, and erucic acid on the surface, and these hydrophobic substances often need to be replaced by surface modification with hydrophilic ligands. The unique properties of polyethylene glycol derivatives enable them to provide excellent water solubility, stability, and biocompatibility for inorganic nanoparticles and are used for surface modification of various nanoparticles. One of the existing technologies for modifying inorganic nanoparticles with polyethylene glycol derivatives is the ligand exchange method, that is, a hydrophilic ligand with strong coordination ability and metal ions on the surface of the nanoparticles coordinate to replace the original long-chain fatty acid or fatty amine. This method is usually completed in an organic solvent. The chemical reaction occurring on the surface and interface of such nanoparticles is affected by steric hindrance effects, etc., and its reaction kinetic process is complex and difficult to control. It is very difficult to completely replace all the long-chain fatty acids or fatty amines in the inorganic nanoparticles. Therefore, the composition of the reaction product is very complex after the reaction, generally including: inorganic nanoparticles modified with polyethylene glycol derivatives with relatively complete ligand exchange, inorganic nanoparticles with incomplete ligand exchange and residual long-chain fatty acids or fatty amines on the surface, free polyethylene glycol derivatives, replaced long-chain fatty acids or fatty amines, organic salts, and organic solvents. Separating and purifying inorganic nanoparticles modified with polyethylene glycol derivatives with relatively complete ligand exchange from these complex components faces the removal of various hydrophilic and hydrophobic ligands and complex nanoparticles on the surface, presenting great technical challenges.

[0003] The existing purification methods for polyethylene glycol derivative-modified inorganic nanoparticles mainly include high-speed centrifugation purification and filtration purification. Chinese Patent Publication No. CN115770883A, a method for phase transfer of surface-modified inorganic nanomaterials, discloses high-speed purification of a small amount of inorganic nanomaterials by high-speed centrifugation. However, when using the high-speed centrifugation method to purify inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives, a poor solvent of polyethylene glycol needs to be added, resulting in the sedimentation of nanoparticles with complete ligand exchange, together with nanoparticles with incomplete ligand exchange and free polyethylene glycol derivatives, which are difficult to separate and are mixed in the product.

[0004] The nanofiltration membrane of the filtration and purification method can retain nanoparticles and filter out free polyethylene glycol derivatives and other small molecule impurities with sizes smaller than the pore size of the nanofiltration membrane, showing potential for industrial production. Chinese Patent Publication CN103769608A, a method for separating silver nanoparticles, discloses a method for separating silver nanoparticles with particle sizes larger than the membrane pore size through ultrafiltration membranes and nanofiltration membranes. However, there are still the following technical problems in purifying inorganic nanoparticles modified with low molecular weight polyethylene glycol derivatives by the nanofiltration membrane filtration method: 1. Limitations in hydrodynamic size proximity. Due to the flexible backbone of polyethylene glycol, the hydrodynamic size of inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives in solution is not significantly different from that of inorganic nanoparticles modified with long-chain fatty acids or fatty amines with rigid backbones. Existing nanofiltration membranes often retain inorganic nanoparticles modified with polyethylene glycol derivatives while also retaining inorganic nanoparticles with similar sizes that have incomplete ligand exchange and residual long-chain fatty acids or fatty amines on the surface, making it difficult to efficiently and accurately distinguish between the two; 2. Prone to forming aggregates and damaging the nanofiltration membrane. Since inorganic nanoparticles modified with polyethylene glycol derivatives are affected by various impurities in the reaction stock solution during membrane filtration, especially the fact that some long-chain fatty acids or fatty amines themselves have surfactant properties, a large amount of foaming and emulsification phenomena will inevitably occur during the filtration cycle. This makes the inorganic nanoparticles modified with polyethylene glycol derivatives extremely prone to aggregation, destroying their stability, and at the same time causing damage to the nanofiltration membrane and reducing the service life of the nanofiltration membrane. These factors limit the application and popularization of this process in large-scale production.

[0005] In summary, when purifying inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives using existing technologies, significant limitations still exist. To overcome these challenges, there is an urgent need to provide a simpler, faster, more efficient, and cost-saving purification method to separate inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives with higher purity and stability, so as to meet the application and popularization of such materials in large-scale production and be applied and developed in a wider range of fields. Summary of the Invention

[0006] In view of this, the purpose of the present invention is to overcome the deficiencies of existing technologies in purifying inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives, and provide a purification method for inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives, which is characterized by including the following steps:

[0007] S1: Preparation of stock solution: The stock solution of inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives obtained by the ligand exchange method contains inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives with a molecular weight of 600 - 6000 Da, free polyethylene glycol derivatives, inorganic nanoparticles with incomplete ligand exchange and residual long-chain fatty acids and / or fatty amines on the surface, long-chain fatty acids and / or fatty amines, organic solvents, metal organic salts and inorganic salt impurities, where the organic solvents are one or more of tetrahydrofuran, chloroalkanes, toluene, ethanol, and N,N-dimethylformamide;

[0008] S2: Alkane sedimentation: Alkanes are added to the stock solution, and the volume ratio of the stock solution to the alkanes ranges from [1:10, 1:1]. The alkanes are straight-chain or branched-chain alkanes composed of 5 - 10 carbon atoms, and an alkane sedimentation solution is generated;

[0009] S3: Alkane washing: The alkane sedimentation solution is stirred at room temperature and then left to stand. The supernatant is removed, and the remaining lower-layer waxy solid-liquid mixture is dried to obtain a solid crude product;

[0010] S4: Acid dissolution: A hydrochloric acid solution with a pH value of 5 - 6.5 is added to the solid crude product to make the concentration of the solid crude product [10, 100] mg / mL, and an acid dissolution product is obtained;

[0011] S5: Ether solvent extraction and phase separation: Ether solvents are added to the acid dissolution product, and the volume ratio of the acid dissolution product to the ether solvents ranges from [1:5, 2:1]. After stirring and standing, the supernatant is removed to obtain a lower-layer product;

[0012] S6: Nanofiltration membrane separation: According to the core size of the inorganic nanoparticles, the pore size of the nanofiltration membrane is selected, and the lower-layer product is separated by the nanofiltration membrane. The unfiltered material is the purified inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives.

[0013] In one embodiment of the present invention, in S1, the polyethylene glycol derivative modification of the inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives is the introduction of one or more of carboxyl, phosphate, catechol, mercapto, hydroxyl functional groups, and ethoxyphenyl functional groups into polyethylene glycol.

[0014] In one embodiment of the present invention, in S1, the inorganic nanoparticles of the inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives are one or more of ferrite nanoparticles, ultrasmall manganese ferrite nanoparticles, ultrasmall manganese zinc ferrite nanoparticles, gold nanoparticles, silver nanoparticles, quantum dot nanoparticles, upconversion nanoparticles, and hafnium oxide nanoparticles.

[0015] In one embodiment of the present invention, in S3, the remaining lower-layer waxy solid-liquid mixture is dried by drying the remaining lower-layer waxy solid-liquid mixture with a vacuum dryer. The drying conditions are that the vacuum degree is not less than 0.6 MPa, the temperature is 30°C - 60°C, and the drying time is not less than 30 min.

[0016] In one embodiment of the present invention, in S4, the hydrochloric acid solution is an aqueous hydrochloric acid solution or an alcoholic hydrochloric acid solution.

[0017] In one embodiment of the present invention, in S4, the alcohol in the alcoholic hydrochloric acid solution is one or a mixture of ethanol, isopropanol, and methanol.

[0018] In one embodiment of the present invention, in S5, the ether solvent is one or a mixture of diethyl ether, propyl ether, butyl ether, dichlorodiethyl ether, and anisole.

[0019] In one embodiment of the present invention, in S6, the selected nanofiltration membrane pore size satisfies: when the core size of the inorganic nanoparticles is between 2 - 5 nm, a nanofiltration membrane with a pore size of 2 - 3 nm is selected; when the core size of the inorganic nanoparticles is between 5 - 10 nm, a nanofiltration membrane with a pore size of 3 - 6 nm is selected; when the core size of the inorganic nanoparticles is greater than 10 nm, a nanofiltration membrane with a pore size of 8 - 12 nm is selected.

[0020] In one embodiment of the present invention, in S6, the nanofiltration membrane is one or a combination of a cellulose membrane, a ceramic membrane, a polyimide membrane, and a polyethersulfone membrane.

[0021] In one embodiment of the present invention, in S6, the separation of the lower-layer product by the nanofiltration membrane is to separate the lower-layer product by the nanofiltration membrane of a spiral-wound nanofiltration device.

[0022] In one embodiment of the present invention, in S6, the separation of the lower-layer product by the nanofiltration membrane is to separate the lower-layer product by the nanofiltration membrane of a spiral-wound nanofiltration device, with a pressure of 0.1 - 0.5 MPa, an operating temperature of 15°C - 60°C, and the number of cycles not less than 2 times.

[0023] In the second aspect of the present invention, a purified product obtained by a method for purifying inorganic nanoparticles modified with a medium- and low-molecular-weight polyethylene glycol derivative, characterized in that in S1, a stock solution is prepared, and the stock solution of inorganic nanoparticles modified with a medium- and low-molecular-weight polyethylene glycol derivative obtained by the ligand exchange method contains ultrasmall manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligands. , free dopamine - polyethylene glycol - ethoxybenzene ligand, ultrasmall manganese ferrite nanoparticles with incomplete ligand exchange and residual long-chain fatty acids and / or fatty amines on the surface, long-chain fatty acids and / or fatty amines, organic solvents, metal organic salts and inorganic salt impurities, and the purified product obtained after S2 - S5 is ultrasmall manganese ferrite nanoparticles modified with dopamine - polyethylene glycol - ethoxybenzene ligand not less than 94.5% , less than 5% free dopamine - polyethylene glycol - ethoxybenzene ligand, less than 0.5% long-chain fatty acid or fatty amine.

[0024] In the third aspect of the present invention, a purified product obtained by a method for purifying inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives, characterized in that in S1, a stock solution is prepared, and the stock solution of inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives obtained by the ligand exchange method contains ultrasmall manganese zinc ferrite nanoparticles modified with ethoxybenzene with a surface metal ion to surface ligand number ratio of 3:1 , free ethoxybenzene, ultrasmall manganese zinc ferrite nanoparticles with incomplete ligand exchange and residual long-chain fatty acids and / or fatty amines on the surface, long-chain fatty acids and / or fatty amines, organic solvents, metal organic salts and inorganic salt impurities, and the purified product obtained after S2 - S5 is ultrasmall manganese zinc ferrite modified with ethoxybenzene with a surface metal ion to surface ligand number ratio of 3:1 not less than 95.5% , less than 3.5% free ethoxybenzene, less than 1% long-chain fatty acid or fatty amine.

[0025] Compared with the prior art, the method of the present application has the following beneficial technical effects:

[0026] 1) Solved the key separation problem, ensured high purity and stability, successfully removed unreacted inorganic nanoparticles that are difficult to separate by nanofiltration membranes and substances that cause emulsification, effectively overcome the separation limitation caused by similar hydrodynamic sizes during single nanofiltration membrane separation, and the agglomeration and emulsification problems caused by long-chain fatty acids and / or fatty amines. For inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives purified by this method, the content control of free polyethylene glycol derivatives, long-chain fatty acids or fatty amines is better than that of the prior art.

[0027] 2) Improved the separation efficiency of the nanofiltration membrane. Using this method to purify inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives reduced the volume of the solution to be treated by the nanofiltration equipment. In one embodiment, using the method provided by this method, the 4L tetrahydrofuran mixed solution to be treated in the prior art solution was changed to 1L aqueous solution, and the treatment volume was reduced to 1 / 4, effectively improving the use efficiency of the nanofiltration equipment.

[0028] 3) Extend the equipment life and reduce costs. After adopting this solution, the nanofiltration equipment hardly comes into contact with organic solvents, avoiding damage to the equipment and the nanofiltration membrane caused by organic solvents. Moreover, due to almost no emulsification and agglomeration phenomena, the pressure required for the nanofiltration process is lower, and the choice of nanofiltration membrane materials is not restricted, and more economical aqueous filters can be selected.

[0029] 4) The purified product obtained by the method of purifying inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives has good physical and chemical stability, enhanced biocompatibility, improved its functionality in specific applications, especially showing good application prospects in the biomedical field and the new energy field. The purified product of the present invention reduces potential toxicity and immune responses, enhances its biocompatibility, improves the performance of electrode materials, extends the equipment service life, and improves the photoelectric conversion efficiency of solar cells. Brief Description of the Drawings

[0030] The drawings are used to provide a further understanding of the present invention and constitute a part of the specification. Together with the embodiments of the present invention, they are used to explain the present invention and do not constitute a limitation to the present invention. In the drawings:

[0031] Figure 1 It is a flow chart of the method for purifying inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives of the present invention;

[0032] Figure 2 It is a transmission electron microscope image of ultrasmall manganese ferrite nanoparticles modified with dopamine - polyethylene glycol - ethoxybenzene ligand purified by the present invention;

[0033] Figure 3 It is the hydrodynamic size of the dynamic light scattering characterization of ultrasmall manganese ferrite nanoparticles modified with dopamine - polyethylene glycol - ethoxybenzene ligand purified by the present invention;

[0034] Figure 4 It is a schematic diagram of the detection of oleic acid and erucic acid contents of ultrasmall manganese ferrite nanoparticles modified with dopamine - polyethylene glycol - ethoxybenzene ligand purified by the present invention;

[0035] Figure 5 It is the relaxation rate of ultrasmall manganese ferrite nanoparticles modified with dopamine - polyethylene glycol - ethoxybenzene ligand purified by the present invention before and after storage for 6 months;

[0036] Figure 6 It is a transmission electron microscope image of 20nm magnetite modified with carboxyl - terminated polyethylene glycol purified by the present invention;

[0037] Figure 7 It is the hydrodynamic size of the dynamic light scattering characterization of 20nm magnetite modified with carboxyl - terminated polyethylene glycol purified by the present invention;

[0038] Figure 8 Transmission electron microscopy image of phosphorylated polyethylene glycol modified 20 nm gold nanoparticles purified by the present invention;

[0039] Figure 9 Hydrodynamic size characterized by dynamic light scattering of phosphorylated polyethylene glycol modified 20 nm gold nanoparticles purified by the present invention;

[0040] Figure 10 Transmission electron microscopy image of ultrasmall manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligand obtained in Comparative Example 2;

[0041] Figure 11 Hydrodynamic size characterized by dynamic light scattering of ultrasmall manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligand obtained in Comparative Example 2. Detailed implementation manners Detailed implementation manner 1

[0043] Combined with Figure 1 , in a specific implementation manner of the present invention, a reaction stock solution is obtained by the ligand exchange method. 10 g of ultrasmall manganese ferrite nanoparticles are dissolved in 1 L of tetrahydrofuran and then added dropwise to a 3 L tetrahydrofuran solution of 50 g of dopamine-polyethylene glycol-ethoxybenzene ligand. The reaction is carried out at 60 °C for 5 h. After the reaction, the resulting stock solution contains ultrasmall manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligand, ultrasmall manganese ferrite nanoparticles with incomplete ligand exchange and residual oleic acid and erucic acid on the surface, free dopamine-polyethylene glycol-ethoxybenzene ligand, replaced oleic acid, erucic acid and oleates, erucates. The steps for purifying the stock solution of inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives include:

[0044] S1: Preparation of stock solution: A stock solution of ultrasmall manganese ferrite nanoparticles modified with 2000 Da dopamine-polyethylene glycol-ethoxybenzene ligand obtained by the ligand exchange method, which contains ultrasmall manganese ferrite nanoparticles modified with 2000 Da dopamine-polyethylene glycol-ethoxybenzene ligand, ultrasmall manganese ferrite nanoparticles with incomplete ligand exchange and residual oleic acid and erucic acid on the surface, free dopamine-polyethylene glycol-ethoxybenzene ligand, replaced oleic acid, erucic acid and oleates, erucates. These impurities and products are mixed in about 4 L of tetrahydrofuran;

[0045] S2: Alkane sedimentation: 4 L of petroleum ether is added to about 4 L of the ligand exchange reaction stock solution to generate an alkane sedimentation solution. In this step, the ligand exchange reaction is terminated by adding petroleum ether to the ligand exchange reaction stock solution, and ultrasmall manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligand and free dopamine-polyethylene glycol-ethoxybenzene ligand are sedimented from the ligand exchange reaction stock solution;

[0046] S3: Alkane Washing: The alkane sedimentation liquid is stirred at room temperature and then allowed to stand. The supernatant is removed, and the remaining lower-layer waxy solid-liquid mixture is dried to obtain approximately 45 g of the solid primary product. The supernatant discarded in this step contains surface residual oleic acid and erucic acid in the ultra-small manganese ferrite nanoparticles with incomplete ligand exchange, partially replaced oleic acid and erucic acid, and the organic solvent tetrahydrofuran. The impurities in the solid primary product mainly remain free dopamine-polyethylene glycol-ethoxybenzene ligands, oleates, erucates, and partially unreacted oleic acid and erucic acid contained in the ultra-small manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligands;

[0047] S4: Acid Dissolution: 0.45 L of hydrochloric acid aqueous solution with a pH value of 6.5 is added to the solid primary product to obtain an acid dissolution product with a concentration of approximately 100 mg / mL. In this step, a small amount of hydrochloric acid strips partially unreacted oleic acid and erucic acid in the ultra-small manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligands, and converts oleate and erucate impurities into the corresponding oleic acid, erucic acid, and inorganic salts;

[0048] S5: Ether Solvent Extraction and Phase Separation: 2.25 L of methyl tert-butyl ether is added to the acid dissolution product. After stirring and standing, the supernatant is removed. The supernatant is the organic phase solution, and the lower-layer product is obtained. The lower-layer product is the aqueous phase. In this step, methyl tert-butyl ether extracts and removes oleic acid, erucic acid, oleates, and erucates, and also extracts and removes some hydrogen chloride. The lower-layer product obtained after this step includes free dopamine-polyethylene glycol-ethoxybenzene ligands and inorganic salt impurities;

[0049] S6: Nanofiltration Membrane Separation: A nanofiltration membrane with a pore size of 3 nm is selected, and the lower-layer product is separated through the nanofiltration membrane to obtain 3 nm ultra-small manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligands in the aqueous phase. Specific Embodiment 2

[0051] Combined with Figure 1 , a specific embodiment of the present invention, a reaction stock solution is obtained by the ligand exchange method. 10 g of oleylamine-coated 6 nm gold nanoparticles are dissolved in 0.5 L of chloroform and then mixed with 2 L of a chloroform solution of 40 g of phosphorylated polyethylene glycol with a number average molecular weight of approximately 600 Da. The reaction is carried out at 35 °C for 12 h. The steps for purifying the reaction stock solution include:

[0052] S1: Preparation of Stock Solution: A stock solution of 600 Da phosphorylated polyethylene glycol-modified gold nanoparticles obtained by the ligand exchange method contains 600 Da phosphorylated polyethylene glycol-modified gold nanoparticles, free phosphorylated polyethylene glycol, gold nanoparticles with surface residual oleylamine due to incomplete ligand exchange, and replaced oleylamine. These impurities are mixed with the product in approximately 2.5 L of chloroform to obtain 2.5 L of the stock solution;

[0053] S2: Alkane sedimentation: 25 L of n-pentane is added to the stock solution to obtain an alkane sedimentation solution;

[0054] S3: Alkane washing: The alkane sedimentation solution is stirred at room temperature and then allowed to stand. After the phosphorylated polyethylene glycol-modified gold nanoparticles settle, the supernatant is removed. The supernatant contains the replaced oleylamine and chloroform. The remaining 0.8 L of waxy solid-liquid mixture at the bottom layer is dried to obtain 30 g of a solid crude product;

[0055] S4: Acid dissolution: 3 L of hydrochloric acid solution with a pH of 5 is added to the solid crude product to make the concentration of the solid crude product 10 mg / mL, obtaining 3 L of an acid dissolution product;

[0056] S5: Ether solvent extraction and phase separation: 15 L of methyl tert-butyl ether is added to the acid dissolution product. After stirring and standing, the supernatant is removed. The supernatant is an organic phase solution, and the product at the bottom layer is obtained. The product at the bottom layer is an aqueous phase;

[0057] S6: Nanofiltration membrane separation: According to the core size of the phosphorylated polyethylene glycol-modified gold nanoparticles, a nanofiltration membrane with a pore size of 5 nm is selected, and the product at the bottom layer is separated through the nanofiltration membrane. The unfiltered product is the purified phosphorylated polyethylene glycol-modified gold nanoparticles. Specific Embodiment 3

[0059] Combined with Figure 1 , in a specific embodiment of the present invention, the steps for purifying the ligand exchange reaction stock solution of carboxyl-terminated polyethylene glycol-modified 20-nm iron oxide nanoparticles include:

[0060] S1: Preparation of stock solution: The stock solution of inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives obtained by the ligand exchange method contains 6000 Da of carboxyl-terminated polyethylene glycol-modified iron oxide nanoparticles, iron oxide nanoparticles with residual oleic acid on the surface due to incomplete ligand exchange, the replaced oleic acid, and oleates. These impurities are mixed with the product in about 4 L of toluene to obtain 4 L of stock solution;

[0061] S2: Alkane sedimentation: 4 L of n-pentane is added to the stock solution to obtain an alkane sedimentation solution;

[0062] S3: Alkane washing: The alkane sedimentation solution is stirred at room temperature and then allowed to stand. After the carboxyl-terminated polyethylene glycol-modified iron oxide nanoparticles settle, the supernatant is removed. The supernatant contains oleic acid, iron oxide nanoparticles with residual oleic acid on the surface due to incomplete ligand exchange, and toluene. The remaining 1.2 L of waxy solid-liquid mixture at the bottom layer is dried to obtain 40 g of a solid crude product;

[0063] S4: Acid Dissolution: Add 0.4 L of hydrochloric acid solution with a pH value of 6.5 to the solid primary product to make the concentration of the solid primary product 100 mg / mL, obtaining 0.4 L of acid dissolution product;

[0064] S5: Ether Solvent Extraction and Phase Separation: Add 0.2 L of methyl tert-butyl ether to the acid dissolution product, stir and then let it stand, remove the supernatant. The supernatant is the organic phase solution, and the lower layer product is obtained, which is the aqueous phase;

[0065] S6: Nanofiltration Membrane Separation: According to the core size of the carboxyl-terminated polyethylene glycol-modified iron oxide nanoparticles, select a nanofiltration membrane with a pore size of 10 nm, and separate the lower layer product through the nanofiltration membrane. The unfiltered product is the purified carboxyl-terminated polyethylene glycol-modified iron oxide nanoparticles. Specific Embodiment 4

[0067] Combined with Figure 1 , a specific embodiment of the present invention uses the ligand exchange method to obtain the reaction stock solution. 10 g of ultra-small manganese ferrite nanoparticles are dissolved in 1 L of tetrahydrofuran and then dropped into a 3 L tetrahydrofuran solution of 50 g of dopamine-polyethylene glycol-ethoxybenzene ligand, and reacted at 60 °C for 5 h. After the reaction, the obtained stock solution contains dopamine-polyethylene glycol-ethoxybenzene ligand-modified ultra-small manganese ferrite nanoparticles, ultra-small manganese ferrite nanoparticles with incomplete ligand exchange and residual oleic acid and erucic acid on the surface, free dopamine-polyethylene glycol-ethoxybenzene ligand, replaced oleic acid, erucic acid, oleate, and erucate. The steps for purifying the stock solution of inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives include:

[0068] S1: Preparation of Stock Solution: The stock solution of ultra-small manganese ferrite nanoparticles modified with 2000 Da dopamine-polyethylene glycol-ethoxybenzene ligand obtained by the ligand exchange method contains ultra-small manganese ferrite nanoparticles modified with 2000 Da dopamine-polyethylene glycol-ethoxybenzene ligand, ultra-small manganese ferrite nanoparticles with incomplete ligand exchange and residual oleic acid and erucic acid on the surface, free dopamine-polyethylene glycol-ethoxybenzene ligand, replaced oleic acid, erucic acid, and their oleates and erucates. These impurities are mixed with the product in about 4 L of tetrahydrofuran;

[0069] S2: Alkane Sedimentation: Add 4 L of petroleum ether to about 4 L of ligand exchange reaction stock solution to generate an alkane sedimentation solution. In this step, the ligand exchange reaction is terminated by adding petroleum ether to the ligand exchange reaction stock solution, and the ultra-small manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligand and free ligand are sedimented from the ligand exchange reaction stock solution;

[0070] S3: Alkane washing: The alkane sedimentation liquid is stirred at room temperature and then left to stand. The supernatant is removed, and the remaining lower-layer waxy solid-liquid mixture is dried to obtain approximately 40 g of the solid primary product. The supernatant discarded in this step contains the ultra-small manganese ferrite nanoparticles with residual oleic acid and erucic acid on the surface due to incomplete ligand exchange, partially replaced oleic acid and erucic acid, and the organic solvent tetrahydrofuran. The main impurities remaining in the solid primary product are the free dopamine-polyethylene glycol-ethoxybenzene ligand, oleate, erucate, and partially unreacted oleic acid and erucic acid contained in the ultra-small manganese ferrite nanoparticles modified with the dopamine-polyethylene glycol-ethoxybenzene ligand;

[0071] S4: Acid dissolution: 4 L of hydrochloric acid aqueous solution with a pH of 6.5 is added to the solid primary product to obtain an acid dissolution product with a concentration of approximately 10 mg / mL. In this step, a small amount of hydrochloric acid strips the partially unreacted oleic acid and erucic acid in the ultra-small manganese ferrite nanoparticles modified with the dopamine-polyethylene glycol-ethoxybenzene ligand, and converts the oleate and erucate impurities into the corresponding oleic acid, erucic acid, and inorganic salts;

[0072] S5: Ether solvent extraction and phase separation: 2 L of methyl tert-butyl ether is added to the acid dissolution product, stirred and then left to stand. The supernatant is removed. The supernatant liquid is the organic phase solution, and the lower-layer product is obtained. The lower-layer product is the aqueous phase. In this step, methyl tert-butyl ether extracts and removes oleic acid, erucic acid, oleate, and erucate, and also extracts and removes part of the hydrogen chloride. After this step, the main residual impurities in the obtained lower-layer product are the free dopamine-polyethylene glycol-ethoxybenzene ligand and inorganic salt impurities;

[0073] S6: Nanofiltration membrane separation: A nanofiltration membrane with a pore size of 3 nm is selected, and the lower-layer product is separated through the nanofiltration membrane to obtain the 3-nm ultra-small manganese ferrite nanoparticles modified with the dopamine-polyethylene glycol-ethoxybenzene ligand in the aqueous phase. Specific Embodiment 5

[0075] Combined with Figure 1-5 , a specific embodiment of the present invention uses the ligand exchange method to obtain the reaction stock solution. 10 g of ultra-small manganese ferrite nanoparticles are dissolved in 1 L of tetrahydrofuran and then dropped into a 3 L tetrahydrofuran solution of 50 g of the dopamine-polyethylene glycol-ethoxybenzene ligand. The reaction is carried out at 60 °C for 5 h. After the reaction, the obtained stock solution contains the ultra-small manganese ferrite nanoparticles modified with the dopamine-polyethylene glycol-ethoxybenzene ligand, the ultra-small manganese ferrite nanoparticles with residual oleic acid and erucic acid on the surface due to incomplete ligand exchange, the free dopamine-polyethylene glycol-ethoxybenzene ligand, the replaced oleic acid, erucic acid, oleate, and erucate. The steps for purifying the stock solution of the inorganic nanoparticles modified with the medium and low molecular weight polyethylene glycol derivatives include:

[0076] S1: Preparation of stock solution: The stock solution of inorganic nanoparticles modified by medium and low molecular weight polyethylene glycol derivatives obtained by ligand exchange method contains ultrafine manganese ferrite nanoparticles modified by dopamine-polyethylene glycol-ethoxybenzene ligand with a molecular weight of 2000 Da, incompletely reacted ultrafine manganese ferrite nanoparticles, free dopamine-polyethylene glycol-ethoxybenzene ligand, replaced oleic acid, erucic acid and oleates, erucates. These impurities are mixed with the product in about 4 L of tetrahydrofuran;

[0077] S2: Alkane sedimentation: 10 L of petroleum ether is added to 4 L of the stock solution to generate an alkane sedimentation solution;

[0078] S3: Alkane washing: The alkane sedimentation solution is stirred at room temperature and then left to stand. The supernatant is removed, and the remaining lower layer of about 1 L of waxy solid-liquid mixture is dried in a vacuum dryer. The drying conditions are a vacuum degree of 0.8 MPa, a temperature of 30 °C, and a drying time of 30 min to obtain 45 g of a solid primary product;

[0079] S4: Acid dissolution: 1 L of hydrochloric acid solution with a pH value of 6.5 is added to the solid primary product to obtain an acid dissolution product with a concentration of 45 mg / mL;

[0080] S5: Ether solvent extraction and phase separation: 1 L of methyl tert-butyl ether is added to the acid dissolution product, stirred and then left to stand. The upper organic phase is removed. After repeating this step twice, the lower layer product is obtained;

[0081] S6: Nanofiltration membrane separation: A nanofiltration membrane with a pore size of 3 nm is selected, and the lower layer product is separated by the nanofiltration membrane. The aqueous phase product is added to a spiral wound nanofiltration device. The operating pressure is set to 0.2 MPa, the operating temperature is set to 30 °C, the circulation is started, and the filtrate is discarded. During the circulation process, ultrapure water is added in time to keep the circulating liquid in the device not lower than the minimum circulation volume. After circulating 10 times, a nanofiltration membrane separation concentrate is obtained. The concentrate is the 3-nm ultrafine manganese ferrite nanoparticles modified by dopamine-polyethylene glycol-ethoxybenzene ligand in the aqueous phase.

[0082] After the treatments of S1 to S5 in this example, the system to be filtered is changed from a 4-L tetrahydrofuran solution to a 1-L aqueous solution, and the impurities in the solution do not include surfactants such as oleic acid and erucic acid, eliminating the emulsification and aggregation phenomena during the nanofiltration process. The electron microscope of the purified 3-nm ultrafine manganese ferrite nanoparticles modified by dopamine-polyethylene glycol-ethoxybenzene ligand is as Figure 2 shown, indicating that the size of the purified 3-nm ultrafine manganese ferrite nanoparticles modified by dopamine-polyethylene glycol-ethoxybenzene ligand is uniform, without obvious aggregation. The three dynamic light scatterings of the 3-nm ultrafine manganese ferrite nanoparticles modified by dopamine-polyethylene glycol-ethoxybenzene ligand are as Figure 3The measured hydrodynamic size distribution is concentrated around 10 nm, with a polydispersity index of 0.19 and very good reproducibility. To detect the content of free polyethylene glycol derivatives in the product, 2 mL of the ultra-small manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligand was taken and centrifuged at 3000 g for 20 min in a 10 KD ultrafiltration tube. The supernatant was taken, and the polyethylene glycol derivatives in the supernatant were detected with reference to General Rule 3202 of the Chinese Pharmacopoeia 2020 Edition. The content of free polyethylene glycol derivatives was measured to be 1.3%. The residual amounts of oleic acid and erucic acid in the product were detected by gas chromatography. The detection method refers to the quantitative analysis of oleic acid in sodium oleate in the Chinese Pharmacopoeia 2020 Edition. The detection results are as Figure 4 shown. 1 is the internal standard, 2 is the corresponding peak of oleic acid, and 3 is the corresponding peak of erucic acid. The total content of oleic acid and erucic acid was calculated to be 0.14%.

[0083] As an index extremely sensitive to changes in material properties, the relaxation rate plays a key role in evaluating material stability. In this scheme, we used a 0.5 T relaxation rate measuring instrument to monitor the purified 3 nm ultra-small manganese ferrite nanoparticles modified with dopamine-polyethylene glycol. As Figure 5 shown, after a storage period of up to 6 months, the relaxation rate of the nanoparticles did not change significantly. Specific Embodiment 6

[0085] Combined with Figure 1 、 Figure 6 、 Figure 7 , in a specific embodiment of the present invention, the steps for purifying the ligand exchange reaction stock solution containing 20 nm iron tetroxide modified with 6000 Da carboxyl-terminated polyethylene glycol include:

[0086] S1: Preparation of the stock solution: The stock solution of inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives obtained by the ligand exchange method contains 20 nm iron tetroxide modified with 6000 Da carboxyl-terminated polyethylene glycol, iron tetroxide nanoparticles with incomplete ligand exchange and residual oleic acid on the surface, free carboxyl-terminated polyethylene glycol, the replaced oleic acid and oleate. These impurities are mixed with the product in about 4 L of toluene;

[0087] S2: Alkane sedimentation: 10 L of petroleum ether was added to 4 L of the stock solution to form an alkane sedimentation solution;

[0088] S3: Alkane washing: The alkane sedimentation solution was stirred at room temperature and then allowed to stand. The supernatant was removed, and the remaining lower-layer waxy solid-liquid mixture was dried with a vacuum dryer to obtain 40 g of a solid primary product;

[0089] S4: Acid dissolution: 1.5 L of a hydrochloric acid ethanol solution with a pH of 6.5 was added to the solid primary product to obtain an acid dissolution product;

[0090] S5: Ether solvent extraction and phase separation: Add 10 L of isopropyl ether to the acid-dissolved product, stir and then let it stand. Remove the upper organic phase to obtain the lower-layer product.

[0091] S6: Nanofiltration membrane separation: Select a nanofiltration membrane with a pore size of 10 nm. Dissolve the lower-layer product in ethanol and add it to a spiral-wound nanofiltration device. Set the operating pressure to 0.1 MPa and the operating temperature to 35 °C. Start the circulation, discard the filtrate to remove the free carboxyl-terminated polyethylene glycol. After circulating 10 times, the unfiltered product is the purified carboxyl-terminated polyethylene glycol-modified iron oxide nanoparticles.

[0092] After the treatments of S1 to S5 in this example, the system to be filtered is changed from 4 L of toluene solution to 1.5 L of ethanol solution, and the impurities in the solution do not include surfactants such as oleic acid and oleate, eliminating the emulsification and agglomeration phenomena during the nanofiltration process. The electron microscope of the purified inorganic nanoparticles modified by medium- and low-molecular-weight polyethylene glycol derivatives in this example is as Figure 6 shown, and the dynamic light scattering characterization is as Figure 7 shown, indicating that the carboxyl-terminated polyethylene glycol-modified iron oxide nanoparticles purified by this method have uniform sizes, a polydispersity index of 0.28, and no obvious agglomeration. Detect the content of free polyethylene glycol derivatives in the product. Take 2 mL of carboxyl-terminated polyethylene glycol-modified iron oxide nanoparticles, centrifuge at 3000 g for 20 min in a 10 KD ultrafiltration tube, and take the lower-layer supernatant. Refer to the general rule 3202 of the Chinese Pharmacopoeia 2020 Edition to detect the polyethylene glycol derivatives in the lower-layer supernatant. The measured content of free polyethylene glycol derivatives is 0.81%. Use gas chromatography to detect the residual amount of oleic acid in the product, and the oleic acid content is 0.25%. Specific Embodiment 7

[0094] Combined with Figure 1 , Figure 8 , Figure 9 , one specific embodiment of the present invention is to obtain a reaction stock solution by ligand exchange. 10 g of 6 nm oleylamine-coated gold nanoparticles are dissolved in 0.5 L of chloroform and then mixed with 2 L of chloroform solution of 40 g of phosphorylated polyethylene glycol with a number average molecular weight of about 600 Da. React at 35 °C for 12 h. The steps for purifying this reaction stock solution include:

[0095] S1: Preparation of stock solution: The stock solution of 6 nm phosphorylated polyethylene glycol-modified gold nanoparticles obtained by ligand exchange contains phosphorylated polyethylene glycol-modified gold nanoparticles, gold nanoparticles with incomplete ligand exchange and residual oleylamine on the surface, free phosphorylated polyethylene glycol, and the replaced oleylamine. These impurities are mixed with the product in about 2.5 L of chloroform.

[0096] S2: Alkane sedimentation: Add 10 L of n-pentane to approximately 2.5 L of the ligand exchange reaction stock solution to generate an alkane sedimentation solution;

[0097] S3: Alkane washing: Stir the alkane sedimentation solution at room temperature and then let it stand. Remove the supernatant, and dry the remaining lower-layer waxy solid-liquid mixture using a vacuum dryer. The drying conditions are a vacuum of 0.8 MPa and drying at 30 °C for 30 min to obtain approximately 30 g of the solid primary product;

[0098] S4: Acid dissolution: Add 1 L of hydrochloric acid aqueous solution with a pH of 6.5 to the solid primary product and dissolve it by ultrasonic treatment to obtain an acid dissolution product;

[0099] S5: Ether solvent extraction and phase separation: Add 0.5 L of methyl tert-butyl ether to the acid dissolution product, stir and then let it stand. After stratification, discard the upper organic phase. Repeat this step twice to obtain the lower-layer aqueous phase product;

[0100] S6: Nanofiltration membrane separation: Select a nanofiltration membrane with a pore size of 5 nm. Add the aqueous phase product to a spiral-wound nanofiltration device, set the operating pressure to 0.2 MPa, set the operating temperature to 30 °C, turn on the circulation, and discard the filtrate to remove free polyethylene glycol derivatives. During the circulation process, add ultrapure water in a timely manner to keep the circulating liquid in the device not lower than the minimum circulation volume. After circulating 10 times, obtain the nanofiltration membrane separation concentrate, and the concentrate is the phosphorylated polyethylene glycol-modified 6-nm gold nanoparticles in the aqueous phase.

[0101] In this example, after the treatments of S1 to S5, the system to be filtered is changed from 2.5 L of chloroform solution to 1 L of aqueous solution, and the impurities in the solution do not include the surfactant oleylamine, eliminating the emulsification and agglomeration phenomena during the nanofiltration process. The electron microscope of the purified aqueous phase particles in this example is as Figure 8 shown, and the dynamic light scattering characterization is as Figure 9 shown, indicating that the size of the aqueous phase particles purified by this method is uniform, there is no obvious agglomeration, and the polydispersity index is 0.26. Detect the content of free polyethylene glycol derivatives in the product. Take 2 mL of the aqueous phase particles, centrifuge at 3000 g for 20 min in a 10 KD ultrafiltration tube, and take the lower-layer clear liquid. Refer to General Chapter 3202 of the Chinese Pharmacopoeia (2020 Edition) to detect the polyethylene glycol derivatives in the lower-layer clear liquid. The measured content of free polyethylene glycol derivatives is 0.9%. Specific Embodiment 8

[0103] Combined with Figure 1 one specific embodiment of the present invention uses the ligand exchange method to obtain a reaction stock solution, including ultrasmall manganese-zinc ferrite nanoparticles modified with ethoxyphenyl with a surface metal ion to surface ligand quantity ratio of 3:1 , free ethoxybenzene, ultrasmall manganese zinc ferrite nanoparticles with incomplete ligand exchange and residual oleic acid on the surface, oleic acid, tetrahydrofuran, oleate. The steps for purifying the stock solution of inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives include:

[0104] S1: Preparation of stock solution: A reaction stock solution is obtained by ligand exchange method, containing ultrasmall manganese zinc ferrite nanoparticles modified with ethoxybenzene with a surface metal ion to surface ligand ratio of 3:1 , free ethoxybenzene, ultrasmall manganese zinc ferrite nanoparticles with incomplete ligand exchange and residual oleic acid on the surface, oleic acid, oleate, and these impurities are mixed with the product in about 4 L of tetrahydrofuran;

[0105] S2: Alkane precipitation: 4 L of petroleum ether is added to about 4 L of the ligand exchange reaction stock solution to form an alkane precipitation solution. In this step, the ligand exchange reaction is terminated by adding petroleum ether to the ligand exchange reaction stock solution, and the ultrasmall manganese zinc ferrite nanoparticles modified with ethoxybenzene ligand and free ethoxybenzene ligand are precipitated from the ligand exchange reaction stock solution;

[0106] S3: Alkane washing: The alkane precipitation solution is stirred at room temperature and then allowed to stand. The supernatant is removed, and the remaining lower layer of waxy solid-liquid mixture is dried to obtain about 40 g of a solid crude product. The supernatant discarded in this step contains ultrasmall manganese zinc ferrite nanoparticles with incomplete ligand exchange and residual oleic acid on the surface, partially replaced oleic acid, and the organic solvent tetrahydrofuran. The main impurities remaining in the solid crude product are free ethoxybenzene ligand, oleate, and partially unreacted oleic acid contained in the ultrasmall manganese zinc ferrite nanoparticles modified with ethoxybenzene ligand;

[0107] S4: Acid dissolution: 4 L of hydrochloric acid aqueous solution with a pH value of 6.5 is added to the solid crude product to obtain an acid dissolution product with a concentration of about 10 mg / mL. In this step, a small amount of hydrochloric acid strips off the partially unreacted oleic acid in the ultrasmall manganese zinc ferrite nanoparticles modified with ethoxybenzene ligand and converts the oleate impurity into the corresponding oleic acid and inorganic salt;

[0108] S5: Ether solvent extraction and phase separation: 2 L of methyl tert-butyl ether is added to the acid dissolution product, stirred and then allowed to stand. The supernatant is removed. The supernatant liquid is an organic phase solution, and the lower layer product is obtained. The lower layer product is an aqueous phase. In this step, methyl tert-butyl ether extracts and removes oleic acid and oleate, and also extracts and removes part of hydrogen chloride. After this step, the main residual impurities in the lower layer product obtained include free ethoxybenzene ligand and inorganic salt impurities;

[0109] S6: Nanofiltration membrane separation: A nanofiltration membrane with a pore size of 3 nm is selected, and the lower layer product is separated through the nanofiltration membrane to obtain ultrasmall manganese zinc ferrite nanoparticles modified with ethoxybenzene ligand with a surface metal ion to surface ligand ratio of 3:1 in the aqueous phase.

[0110] Ultra-small manganese-zinc ferrite nanoparticles modified with ethoxybenzene with a surface metal ion to surface ligand ratio of 3:1 The purity is 95.7%, of which free ethoxybenzene is 3.4% and the oleate impurity content is 0.9%.

[0111] Comparative Example 1

[0112] Purify the reaction stock solution in the same way as in Example 5. When purifying 4 L of the reaction stock solution by high-speed centrifugation, 16 L of ether needs to be added as a poor solvent and centrifuged at a centrifugal force of 5000 g for 5 min. High-speed centrifuges capable of centrifuging 20 L at one time are expensive. Therefore, 10 mL of the stock solution is taken and added to 40 mL of ether for high-speed centrifugation and purification to compare the effects of this method with this scheme. The comparison between the product purified by this scheme and the product purified by Example 5 is shown in Table 1 in detail. Among them, the content of free polyethylene glycol derivative is 6.1%, and the total content of oleic acid and erucic acid is 0.58%.

[0113] Comparative Example 2

[0114] Purify the reaction stock solution in the same way as in Example 5. Without treatment, directly use a nanofiltration device for purification. Select a nanofiltration membrane with a pore size of 3 nm. Add 4 L of the reaction stock solution to a spiral-wound nanofiltration device, set the operating pressure to 0.2 MPa, set the operating temperature to 30 °C, turn on the circulation, discard the filtrate, and keep the circulating liquid in the device not less than the minimum circulation volume during the circulation process. The electron microscope of the aqueous phase particles purified by this method is as Figure 10 shown. It can be seen that the purification method used in Comparative Example 2 resulted in obvious agglomeration of the particles due to serious emulsification during the purification process, and purification could not be completed. The comparison with the product purified by Example 5 is shown in Table 1 in detail. The final treatment system in Table 1 is the liquid volume and solvent that finally need to be treated by the nanofiltration membrane / centrifuge for 4 L of the reaction stock solution. × represents that the impurity content in the product exceeds the detection upper limit due to emulsification and agglomeration. Its hydrodynamic size measured three times is as Figure 11 shown, with multiple peak distributions, also proving that obvious aggregation has occurred.

[0115] Table 1

[0116]

[0117] Thus, it can be seen that the purification method of inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives provided by the present invention can effectively prevent emulsification and agglomeration of inorganic nanoparticles in the nanofiltration membrane, improve the use efficiency of the nanofiltration membrane device, reduce the corrosion of the organic solvent to the nanofiltration membrane device, and at the same time, the content of free polyethylene glycol derivative in the obtained product is low, the hydrodynamic size distribution is concentrated, and the monodispersity is good.

Claims

1. A method for purifying inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives, characterized in that, It includes the following steps: S1: Preparation of stock solution: The stock solution of inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives obtained by ligand exchange method contains inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives with a molecular weight of 600 - 6000 Da, free polyethylene glycol derivatives, inorganic nanoparticles with incomplete ligand exchange and residual long-chain fatty acids and / or fatty amines on the surface, long-chain fatty acids and / or fatty amines, organic solvents, metal organic salts and inorganic salt impurities, where the organic solvent is one or more of tetrahydrofuran, chloroalkane, toluene, ethanol, N,N-dimethylformamide; S2: Alkane sedimentation: An alkane is added to the stock solution, and the volume ratio of the stock solution to the alkane ranges from [1:10, 1:1]. Among them, the alkane is a straight-chain or branched-chain alkane composed of 5 - 10 carbon atoms, and an alkane sedimentation solution is generated; S3: Alkane washing: The alkane sedimentation solution is stirred at room temperature and then left to stand. The supernatant is removed, and the remaining lower-layer waxy solid-liquid mixture is dried to obtain a solid primary product; S4: Acid dissolution: A hydrochloric acid solution with a pH value of 5 - 6.5 is added to the solid primary product to make the concentration of the solid primary product [10, 100] mg / mL, and an acid dissolution product is obtained; S5: Ether solvent extraction and phase separation: An ether solvent is added to the acid dissolution product, and the volume ratio of the acid dissolution product to the ether solvent ranges from [1:5, 2:1]. After stirring and standing, the supernatant is removed to obtain a lower-layer product; S6: Nanofiltration membrane separation: According to the core size of the inorganic nanoparticles, the pore size of the nanofiltration membrane is selected, and the lower-layer product is separated by the nanofiltration membrane. The unfiltered material is the purified inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives.

2. The purification method of the inorganic nanoparticles modified by medium and low molecular weight polyethylene glycol derivatives according to claim 1, characterized in that, In S1, the modification of the inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives with a molecular weight of 600 - 6000 Da is to introduce one or more of carboxyl, phosphate group, catechol, mercapto, hydroxyl, and ethoxybenzene functional groups into polyethylene glycol, and the inorganic nanoparticles are one or more of ferrite nanoparticles, gold nanoparticles, silver nanoparticles, hafnium oxide nanoparticles.

3. The purification method of the inorganic nanoparticles modified by medium and low molecular weight polyethylene glycol derivatives according to claim 1, characterized in that, In S3, the drying of the remaining lower-layer waxy solid-liquid mixture is to dry the remaining lower-layer waxy solid-liquid mixture through a vacuum dryer, and the drying conditions are that the vacuum degree is not less than 0.6 MPa, the temperature is 30°C - 60°C, and the drying time is not less than 30 min.

4. The method for purifying inorganic nanoparticles modified with medium- and low-molecular-weight polyethylene glycol derivatives according to claim 1, characterized in that In S4, the hydrochloric acid solution is an aqueous hydrochloric acid solution or a hydrochloric acid alcohol solution.

5. The purification method of the inorganic nanoparticles modified by medium and low molecular weight polyethylene glycol derivatives according to claim 1, characterized in that, In S5, the ether solvent is one or more mixtures of diethyl ether, propyl ether, butyl ether, dichlorodiethyl ether, and anisole.

6. The purification method of the inorganic nanoparticles modified by medium and low molecular weight polyethylene glycol derivatives according to claim 1, characterized in that, In S6, the selection of the nanofiltration membrane pore size satisfies: when the core size of the inorganic nanoparticles is between 2 - 5 nm, a nanofiltration membrane with a pore size of 2 - 3 nm is selected; when the core size of the inorganic nanoparticles is between 5 - 10 nm, a nanofiltration membrane with a pore size of 3 - 6 nm is selected; when the core size of the inorganic nanoparticles is greater than 10 nm, a nanofiltration membrane with a pore size of 8 - 12 nm is selected.

7. The method for purifying inorganic nanoparticles modified with medium- and low-molecular-weight polyethylene glycol derivatives according to claim 1, characterized in that, In S6, the nanofiltration membrane is one or more combinations of cellulose membrane, ceramic membrane, polyimide membrane, and polyethersulfone membrane.

8. The method for purifying inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives according to claim 1, wherein In S6, the separation of the lower-layer product by the nanofiltration membrane is carried out by the nanofiltration membrane of a spiral-wound nanofiltration device. The pressure is 0.1 - 0.5 MPa, the operating temperature is 15°C - 60°C, and the number of circulation times is not less than 2 times.

9. The method for purifying inorganic nanoparticles modified with medium- and low-molecular-weight polyethylene glycol derivatives according to claim 1, wherein In S1, in the inorganic nanoparticles modified with medium- and low-molecular-weight polyethylene glycol derivatives with a molecular weight of 600 - 6000 Da, the polyethylene glycol derivative modification is the introduction of one or more of carboxyl, phosphate, catechol, mercapto, hydroxyl, and ethoxyphenyl functional groups into polyethylene glycol, and the inorganic nanoparticles are quantum dot nanoparticles.

10. A purified product obtained by a method for purifying inorganic nanoparticles modified with a medium- or low-molecular-weight polyethylene glycol derivative according to any one of claims 1-8, characterized in that, In S1, a stock solution is prepared. The stock solution of the inorganic nanoparticles modified with medium- and low-molecular-weight polyethylene glycol derivatives obtained by the ligand exchange method contains ultrasmall manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxyphenyl ligands, free dopamine-polyethylene glycol-ethoxyphenyl ligands, ultrasmall manganese ferrite nanoparticles with incomplete ligand exchange and residual long-chain fatty acids and / or fatty amines on the surface, long-chain fatty acids and / or fatty amines, organic solvents, metal organic salts, and inorganic salt impurities. The purified product obtained after S2 - S5 is ultrasmall manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxyphenyl ligands not less than 94.5%, free dopamine-polyethylene glycol-ethoxyphenyl ligands less than 5%, and long-chain fatty acids or fatty amines less than 0.5%.

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