Method for purifying inorganic nanoparticles modified by medium-low molecular weight polyethylene glycol derivative and purified product

Abstract

The invention relates to the technical field of production of nano composite materials, in particular to a method for purifying inorganic nano particles modified by medium-low molecular weight polyethylene glycol derivatives. According to the method for purifying the inorganic nanoparticles modified by the medium-low molecular weight polyethylene glycol derivative, provided by the invention, high-purity purification is realized through the combination and sequence of the process steps of stock solution preparation, alkane sedimentation, alkane washing, acid dissolution, ether solvent extraction and phase separation and nanofiltration membrane separation; by purifying the inorganic nanoparticles modified by the medium-low molecular weight polyethylene glycol derivative, the emulsification and agglomeration of the inorganic nanoparticles in the nanofiltration membrane are effectively prevented, the use efficiency of nanofiltration membrane equipment is improved, the corrosion of an organic solvent to the nanofiltration membrane equipment is reduced, and meanwhile, the obtained product is high in purity and high in yield. The preparation method has the advantages of simple process, few free polyethylene glycol derivatives, concentrated hydrodynamic size distribution, good monodispersity and higher industrial application potential, and can meet the requirements of large-scale production.

Description

Technical Field

[0001] The invention relates to the technical field of nano composite material production, in particular to a purification method and purified products of inorganic nano particles modified with medium and low molecular weight polyethylene glycol derivatives. Background Art

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

[0003] The purification methods of inorganic nanoparticles modified with polyethylene glycol derivatives in the prior art mainly include high-speed centrifugation purification method and filtration purification method. Chinese patent publication CN115770883A, a method for phase transfer of surface-modified inorganic nanomaterials, discloses high-speed purification of small-dose inorganic nanomaterials by high-speed centrifugation method. However, when using high-speed centrifugation method to purify inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives, a poor solvent for polyethylene glycol needs to be added, resulting in the complete ligand exchange of nanoparticles, together with the incomplete ligand exchange of nanoparticles and free polyethylene glycol derivatives, which are mixed in the product and difficult to separate.

[0004] The nanofiltration membrane of the filtration purification method can intercept nanoparticles and filter out free polyethylene glycol derivatives and other small molecule impurities whose size is smaller than the pore size of the nanofiltration membrane, and has the potential to be applied in industrial production. Chinese patent publication CN103769608A, a method for separating nanosilver sol, discloses a method for separating nanosilver whose particle size is larger than the membrane pore size by ultrafiltration membrane and nanofiltration membrane. However, the use of nanofiltration membrane filtration to purify low molecular weight polyethylene glycol derivative modified inorganic nanoparticles currently still has the following technical problems: 1. The limitation of similar hydrodynamic size. Due to the flexible skeleton of polyethylene glycol, the hydrodynamic size of medium and low molecular weight polyethylene glycol derivative modified inorganic nanoparticles in solution is not much different from that of long chain fatty acids or fatty amines with rigid skeletons. The existing nanofiltration membrane can often retain inorganic nanoparticles of similar size with incomplete ligand exchange and residual long chain fatty acids or fatty amines on the surface while retaining the inorganic nanoparticles modified by polyethylene glycol derivatives, making it difficult to efficiently and accurately distinguish the two; 2. It is easy to form agglomeration and damage the nanofiltration membrane. Since the inorganic nanoparticles modified by polyethylene glycol derivatives are affected by various impurities in the reaction stock solution when passing through the membrane, especially some long chain fatty acids or fatty amines themselves have the characteristics of surfactants, a large amount of foam and emulsification will inevitably be generated during the filtration cycle, which makes the inorganic nanoparticles modified by polyethylene glycol derivatives very easy to agglomerate, destroying their stability, and also causing damage to the nanofiltration membrane, reducing the service life of the nanofiltration membrane. These factors limit the application and promotion of this process in large-scale production.

[0005] In summary, the existing technology for purifying inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives still faces significant limitations. In order to overcome these challenges, it is urgent 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 promotion of such materials in large-scale production, and to apply and develop them 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 shortcomings of the prior art in purifying inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives, and provide 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: A stock solution of inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives obtained by ligand exchange method, which 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, chloroalkanes, toluene, ethanol, N,N-dimethylformamide; 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], where the alkanes are straight-chain or branched-chain alkanes composed of 5 - 10 carbon atoms, to generate an alkane sedimentation solution; 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, to obtain an acid dissolution product; 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.

[0007] 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.

[0008] 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, hafnium oxide nanoparticles.

[0009] In one embodiment of the present invention, 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 a vacuum degree of not less than 0.6 MPa, a temperature of 30°C - 60°C, and a drying time of not less than 30 min.

[0010] 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.

[0011] In one embodiment of the present invention, in S4, the alcohol of the hydrochloric acid alcohol solution is a mixture of one or more of ethanol, isopropanol, and methanol. In one embodiment of the present invention, in S5, the ether solvent is a mixture of one or more of ethyl ether, propyl ether, butyl ether, dichlorodiethyl ether, and anisole.

[0012] In one embodiment of the present invention, in S6, the pore size of the nanofiltration membrane is selected to meet the following requirements: when the core size of the inorganic nanoparticles is between 2-5nm, a nanofiltration membrane with a pore size of 2-3nm is selected; when the core size of the inorganic nanoparticles is between 5-10nm, a nanofiltration membrane with a pore size of 3-6nm is selected; when the core size of the inorganic nanoparticles is greater than 10nm, a nanofiltration membrane with a pore size of 8-12nm is selected.

[0013] In one embodiment of the present invention, in S6, the nanofiltration membrane is a combination of one or more of a cellulose membrane, a ceramic membrane, a polyimide membrane, and a polyethersulfone membrane.

[0014] In one embodiment of the present invention, in S6, the separation of the lower layer product by the nanofiltration membrane is separation of the lower layer product by the nanofiltration membrane of a roll nanofiltration device.

[0015] In one embodiment of the present invention, in S6, the separation of the lower layer product by nanofiltration membrane is separation of the lower layer product by nanofiltration membrane of a roll nanofiltration device, the pressure is 0.1-0.5MPa, the operating temperature is 15℃-60℃, and the number of cycles is not less than 2 times.

[0016] The second aspect of the present invention is a purified product obtained by a method for purifying inorganic nanoparticles modified with medium- and low-molecular-weight polyethylene glycol derivatives, characterized in that the S1, preparing a stock solution, the inorganic nanoparticle stock solution modified with medium- and low-molecular-weight polyethylene glycol derivatives obtained by a ligand exchange method, comprising ultra-small manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligands , free dopamine-polyethylene glycol-ethoxybenzene ligand, ultra-small manganese ferrite nanoparticles with residual long-chain fatty acids and / or fatty amines on the surface due to incomplete ligand exchange, long-chain fatty acids and / or fatty amines, organic solvents, metal organic acid salts and inorganic salt impurities, and the purified product obtained after S2-S5 is ultra-small manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligands of not less than 94.5% , less than 5% free dopamine-polyethylene glycol-ethoxyphenyl ligand, less than 0.5% long chain fatty acids or fatty amines.

[0017] The third aspect of the present invention is a purified product obtained by a method for purifying inorganic nanoparticles modified by medium- and low-molecular-weight polyethylene glycol derivatives, characterized in that the S1, preparing a stock solution, the inorganic nanoparticle stock solution modified by medium- and low-molecular-weight polyethylene glycol derivatives obtained by the ligand exchange method, comprising ultra-small manganese-zinc ferrite nanoparticles modified with ethoxybenzene having a surface metal ion to surface ligand number ratio of 3:1 , free ethoxybenzene, ultra-small manganese zinc ferrite nanoparticles with residual long-chain fatty acids and / or fatty amines on the surface due to incomplete ligand exchange, long-chain fatty acids and / or fatty amines, organic solvents, metal organic acid salts and inorganic salt impurities, and the purified product obtained after S2-S5 is an ultra-small manganese zinc ferrite nanoparticle modified with ethoxybenzene having a surface metal ion to surface ligand number ratio of not less than 95.5% and a ratio of 3:1. , less than 3.5% free ethoxybenzene, less than 1% long-chain fatty acids or fatty amines.

[0018] Compared with the prior art, the method of the present application has the following beneficial technical effects: 1) The key separation problem is solved, high purity and stability are guaranteed, and unreacted inorganic nanoparticles and substances that cause emulsification that are difficult to separate with nanofiltration membranes are successfully removed, effectively overcoming the separation limitations caused by similar hydrodynamic sizes when using a single nanofiltration membrane, as well as the agglomeration and emulsification problems caused by long-chain fatty acids and / or fatty amines. The inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives purified by this method have better control over the content of free polyethylene glycol derivatives, long-chain fatty acids or fatty amines than the existing technology.

[0019] 2) The separation efficiency of the nanofiltration membrane is improved. The method is used to purify inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives, reducing the volume of solution required for treatment by the nanofiltration equipment. In one embodiment, the method provided by the present invention is used to convert 4L of tetrahydrofuran mixed solution to be treated in the prior art solution into 1L of aqueous solution, reducing the treatment volume to 1 / 4, effectively improving the use efficiency of the nanofiltration equipment.

[0020] 3) Extend the life of the equipment and reduce costs. After adopting this solution, the nanofiltration equipment is almost not in contact with organic solvents, avoiding damage to the equipment and nanofiltration membranes by organic solvents. And because there is almost no emulsification and agglomeration, the pressure required for the nanofiltration process is lower, the choice of nanofiltration membrane material is not limited, and a more economical water filter membrane can be selected.

[0021] 4) The purified product obtained by the method for 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 fields of biomedicine and new energy. The purified product of the present invention reduces potential toxicity and immune responses, enhances its biocompatibility, improves the performance of electrode materials, extends the service life of equipment, and improves the photoelectric conversion efficiency of solar cells. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] 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: Figure 1 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; Figure 2 is a transmission electron microscope image of ultrasmall manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligand purified by the present invention; Figure 3 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; Figure 4 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; Figure 5 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; Figure 6 is a transmission electron microscope image of 20 nm magnetite modified with carboxyl-terminated polyethylene glycol purified by the present invention; Figure 7 is the hydrodynamic size of the dynamic light scattering characterization of 20 nm magnetite modified with carboxyl-terminated polyethylene glycol purified by the present invention; Figure 8 is a transmission electron microscope image of 20 nm gold nanoparticles modified with phosphorylated polyethylene glycol purified by the present invention; Fig. 9 is the hydrodynamic size of the dynamic light scattering characterization of 20 nm gold nanoparticles modified with phosphorylated polyethylene glycol purified by the present invention; Fig.10 is an electron microscope image of ultrasmall manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligand obtained in Comparative Example 2; Fig.11The hydrodynamic size of the ultrasmall manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligand obtained in Comparative Example 2 was characterized by dynamic light scattering. DETAILED DESCRIPTION Specific implementation method 1 Combination Figure 1 In one embodiment of the present invention, a reaction stock solution is obtained by a ligand exchange method. 10 g of ultra-small 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 ligands. The reaction is carried out at 60° C. for 5 hours. After the reaction is completed, the resulting stock solution contains ultra-small manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligands, ultra-small manganese ferrite nanoparticles with residual oleic acid and erucic acid on the surface of incomplete ligand exchange, free dopamine-polyethylene glycol-ethoxybenzene ligands, and the stock solutions of oleic acid, erucic acid, oleate, and erucate after replacement. The steps of purifying the stock solution of inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives include: S1: preparing a stock solution: a stock solution of ultra-small manganese ferrite nanoparticles modified with 2000Da dopamine-polyethylene glycol-ethoxybenzene ligands obtained by a ligand exchange method, comprising ultra-small manganese ferrite nanoparticles modified with 2000Da dopamine-polyethylene glycol-ethoxybenzene ligands, ultra-small manganese ferrite nanoparticles with residual oleic acid and erucic acid on the surface due to incomplete ligand exchange, free dopamine-polyethylene glycol-ethoxybenzene ligands, replaced oleic acid, erucic acid and oleate, erucate, and these impurities are mixed with the product in about 4L of tetrahydrofuran; S2: Alkane precipitation: 4 L of petroleum ether is added to about 4 L of the ligand exchange reaction stock solution to generate 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 ultra-small manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligands and the free dopamine-polyethylene glycol-ethoxybenzene ligands are precipitated from the ligand exchange reaction stock solution; S3: Alkane washing: The alkane precipitate is stirred at room temperature and then allowed to stand, the supernatant is removed, and the remaining waxy solid-liquid mixture at the lower layer is dried to obtain about 45 g of a solid primary product. The supernatant discarded in this step contains 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 an organic solvent, tetrahydrofuran. The impurities in the solid primary product mainly include remaining free dopamine-polyethylene glycol-ethoxybenzene ligands, oleate, erucate, and partially incompletely reacted oleic acid and erucic acid contained in ultra-small manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligands; S4: Acid dissolution: 0.45 L of a hydrochloric acid aqueous solution with a pH value of 6.5 is added to the solid primary product to obtain an acid-dissolved product with a concentration of about 100 mg / mL. In this step, a trace amount of hydrochloric acid is used to partially replace the incomplete oleic acid and erucic acid in the ultra-small manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligand, and the oleate and erucate impurities are converted into the corresponding oleic acid, erucic acid and inorganic salts; S5: Ether solvent extraction and phase separation: add 2.25L methyl tert-butyl ether to the acid-dissolved product, stir and then let stand, remove the supernatant, 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 is used to extract and remove oleic acid, erucic acid and oleate, erucate, and also extract and remove part of the hydrogen chloride. After this step, the lower layer product obtained includes free dopamine-polyethylene glycol-ethoxybenzene ligand and inorganic salt impurities; S6: Nanofiltration membrane separation: A nanofiltration membrane with a pore size of 3 nm is selected to separate the lower layer product through the nanofiltration membrane, thereby obtaining 3 nm ultra-small manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligands in the aqueous phase. Specific implementation method 2 Combination Figure 1 In one embodiment of the present invention, a reaction stock solution is obtained by ligand exchange method, 10 g of 6 nm gold nanoparticles coated with oleylamine are dissolved in 0.5 L chloroform and then in 2 L chloroform solution of 40 g of phosphorylated polyethylene glycol with a number average molecular weight of about 600 Da, and reacted at 35° C. for 12 h. The step of purifying the reaction stock solution comprises: S1: Preparation of stock solution: A stock solution of 600Da phosphorylated polyethylene glycol-modified gold nanoparticles obtained by ligand exchange method, comprising 600Da phosphorylated polyethylene glycol-modified gold nanoparticles, free phosphorylated polyethylene glycol, gold nanoparticles with residual oleylamine on the surface due to incomplete ligand exchange, and replaced oleylamine. These impurities are mixed with the product in about 2.5L of chloroform to obtain 2.5L of stock solution; S2: Alkane precipitation: 25 L of n-pentane was added to the original solution to obtain an alkane precipitation liquid; S3: Alkane washing: The alkane precipitation liquid was stirred at room temperature and then allowed to stand. After the phosphorylated polyethylene glycol-modified gold nanoparticles were precipitated, the supernatant was removed. The supernatant contained the replaced oleylamine and chloroform. The remaining lower layer of 0.8L waxy solid-liquid mixture was dried to obtain 30g of solid initial product. S4: Acid dissolution: 3 L of hydrochloric acid solution with a pH value of 5 was added to the solid primary product to make the concentration of the solid primary product 10 mg / mL, and 3 L of acid-dissolved product was obtained; S5: Ether solvent extraction and phase separation: add 15L of methyl tert-butyl ether to the acid-dissolved product, stir and let stand, remove the supernatant, the supernatant is the organic phase solution, and the lower layer product is obtained, and the lower layer product is the aqueous phase; S6: Nanofiltration membrane separation: According to the core size of the gold nanoparticles modified with phosphorylated polyethylene glycol, the pore size of the nanofiltration membrane is selected to be 5 nm. The lower layer product is separated by the nanofiltration membrane, and the unfiltered material is the purified phosphorylated polyethylene glycol modified gold nanoparticles. Specific implementation method 3 Combination Figure 1 In one embodiment of the present invention, the step of purifying the ligand exchange reaction stock solution of 20 nm ferrosoferric oxide nanoparticles modified with carboxyl-terminated polyethylene glycol comprises: S1: Preparation of stock solution: a stock solution of inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives obtained by ligand exchange method, including 6000Da carboxyl-terminated polyethylene glycol-modified ferroferric oxide nanoparticles, oleic acid ferroferric oxide nanoparticles with incomplete ligand exchange and residual surface oleic acid and oleate, these impurities are mixed with the product in about 4L of toluene to obtain 4L of stock solution; S2: Alkane precipitation: 4 L of n-pentane was added to the original solution to obtain an alkane precipitation solution; S3: Alkane washing: The alkane precipitation liquid was stirred at room temperature and then allowed to stand. After the carboxyl-terminated polyethylene glycol-modified ferroferric oxide nanoparticles were precipitated, the supernatant was removed. The supernatant contained oleic acid, ferroferric oxide nanoparticles with residual oleic acid on the surface due to incomplete ligand exchange, and toluene. The remaining lower layer of 1.2 L waxy solid-liquid mixture was dried to obtain 40 g of a solid initial product. S4: Acid dissolution: 0.4 L of hydrochloric acid solution with a pH value of 6.5 was added to the solid primary product to make the concentration of the solid primary product 100 mg / mL, and 0.4 L of acid-dissolved product was obtained; S5: Ether solvent extraction and phase separation: add 0.2L methyl tert-butyl ether to the acid-dissolved product, stir and let stand, remove the supernatant, the supernatant is the organic phase solution, and the lower layer product is obtained, and the lower layer product is the aqueous phase; S6: Nanofiltration membrane separation: According to the core size of the carboxyl-terminated polyethylene glycol-modified ferrosoferric oxide nanoparticles, a nanofiltration membrane pore size of 10 nm is selected, and the lower layer product is separated by the nanofiltration membrane. The unfiltered material is the purified carboxyl-terminated polyethylene glycol-modified ferrosoferric oxide nanoparticles. Specific implementation method 4 Combination Figure 1In one embodiment of the present invention, a reaction stock solution is obtained by a ligand exchange method. 10 g of ultra-small 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 ligands. The reaction is carried out at 60° C. for 5 hours. After the reaction is completed, the resulting stock solution contains ultra-small manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligands, ultra-small manganese ferrite nanoparticles with residual oleic acid and erucic acid on the surface of incomplete ligand exchange, free dopamine-polyethylene glycol-ethoxybenzene ligands, and the stock solutions of oleic acid, erucic acid, oleate, and erucate after replacement. The steps of purifying the stock solution of inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives include: S1: preparing a stock solution: a stock solution of ultrasmall manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligands of 2000 Da obtained by a ligand exchange method, comprising ultrasmall manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligands of 2000 Da, ultrasmall manganese ferrite nanoparticles with residual oleic acid and erucic acid on the surface due to incomplete ligand exchange, free dopamine-polyethylene glycol-ethoxybenzene ligands, replaced oleic acid, erucic acid and its oleate and erucate, and these impurities are mixed with the product in about 4 L of tetrahydrofuran; S2: Alkane precipitation: 4 L of petroleum ether is added to about 4 L of the ligand exchange reaction stock solution to generate 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 ultra-small manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligands and free ligands are precipitated from the ligand exchange reaction stock solution; S3: Alkane washing: The alkane precipitate is stirred at room temperature and then allowed to stand, the supernatant is removed, and the remaining waxy solid-liquid mixture at the lower layer is dried to obtain about 40 g of a solid initial product. The supernatant discarded in this step contains 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 an organic solvent, tetrahydrofuran. The impurities in the solid initial product mainly include remaining free dopamine-polyethylene glycol-ethoxybenzene ligands, oleate, erucate, and partially incompletely reacted oleic acid and erucic acid contained in ultra-small manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligands; S4: Acid dissolution: 4 L of hydrochloric acid aqueous solution with a pH value of 6.5 is added to the solid primary product to obtain an acid-dissolved product with a concentration of about 10 mg / mL. In this step, a trace amount of hydrochloric acid strips off the partially incompletely reacted oleic acid and erucic acid in the ultra-small manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligand, and converts the oleate and erucate impurities into the corresponding oleic acid, erucic acid and inorganic salts; S5: Ether solvent extraction and phase separation: add 2L of methyl tert-butyl ether to the acid-dissolved product, stir and then let stand, remove the supernatant, the supernatant is the organic phase solution, and the lower layer product is obtained, which is the aqueous phase. In this step, methyl tert-butyl ether is used to extract and remove oleic acid, erucic acid, oleate and erucate, and also extract and remove part of the hydrogen chloride. After this step, the lower layer product obtained includes residual impurities mainly including free dopamine-polyethylene glycol-ethoxybenzene ligands and inorganic salt impurities; S6: Nanofiltration membrane separation: A nanofiltration membrane with a pore size of 3 nm is selected to separate the lower layer product through the nanofiltration membrane, thereby obtaining 3 nm ultra-small manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligands in the aqueous phase. Specific implementation method 5 Combination Figure 1-5 In one embodiment of the present invention, a reaction stock solution is obtained by a ligand exchange method. 10 g of ultra-small 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 ligands. The reaction is carried out at 60° C. for 5 hours. After the reaction is completed, the resulting stock solution contains ultra-small manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligands, ultra-small manganese ferrite nanoparticles with residual oleic acid and erucic acid on the surface of incomplete ligand exchange, free dopamine-polyethylene glycol-ethoxybenzene ligands, and the stock solutions of oleic acid, erucic acid, oleate, and erucate after replacement. The steps of purifying the stock solution of inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives include: S1: Preparation of stock solution: a stock solution of inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives obtained by ligand exchange method, comprising ultra-small manganese ferrite nanoparticles modified with 2000Da dopamine-polyethylene glycol-ethoxybenzene ligands, incompletely reacted ultra-small manganese ferrite nanoparticles, free dopamine-polyethylene glycol-ethoxybenzene ligands, replaced oleic acid, erucic acid and oleate, erucate, and these impurities are mixed with the product in about 4L of tetrahydrofuran; S2: Alkane precipitation: 10L petroleum ether was added to 4L stock solution to generate alkane precipitation liquid; S3: Alkane washing: The alkane precipitate was stirred at room temperature and then allowed to stand, the supernatant was removed, and the remaining lower layer of about 1L waxy solid-liquid mixture was dried in a vacuum dryer under the conditions of vacuum degree 0.8MPa, temperature 30°C, and drying time 30min to obtain 45g of solid initial product; S4: Acid dissolution: Add 1 L of hydrochloric acid solution with a pH value of 6.5 to the solid initial product to obtain an acid-dissolved product with a concentration of 45 mg / mL; S5: Ether solvent extraction and phase separation: add 1L of methyl tert-butyl ether to the acid-dissolved product, stir and let stand, remove the supernatant organic phase, repeat this step twice to obtain the lower layer product; S6: Nanofiltration membrane separation: select a nanofiltration membrane with a pore size of 3nm, separate the lower layer product through the nanofiltration membrane, add the aqueous phase product into the roll nanofiltration equipment, set the operating pressure to 0.2MPa, set the operating temperature to 30℃, start the circulation, discard the filtrate, and add ultrapure water in time during the circulation process to keep the circulating liquid in the equipment not less than the minimum circulation volume. After 10 cycles, the nanofiltration membrane separation concentrate is obtained, and the concentrate is the 3nm ultrasmall manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligands in the aqueous phase.

[0028] In this embodiment, after the treatments from S1 to S5, the system to be filtered is converted from 4L tetrahydrofuran solution to 1L aqueous solution, and the impurities in the solution do not contain surfactants such as oleic acid and erucic acid, eliminating the emulsification and agglomeration phenomena in the nanofiltration process. The electron microscopy of the purified dopamine-polyethylene glycol-ethoxybenzene ligand modified 3nm ultra-small manganese ferrite nanoparticles is as follows: Figure 2 As shown, it shows that the 3nm ultra-small manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligands purified by this method have uniform size and no obvious agglomeration. The triple dynamic light scattering of the 3nm ultra-small manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligands is as follows: Figure 3 The measured hydrodynamic size distribution is concentrated around 10 nm, with a polydispersity index of 0.19 and very good reproducibility. The content of free polyethylene glycol derivatives in the product was detected. 2 mL of ultrasmall manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligands were centrifuged in a 10KD ultrafiltration tube at 3000g for 20 minutes, and the lower clear liquid was taken. The polyethylene glycol derivatives in the lower clear liquid were detected with reference to General Rule 3202 of the 2020 edition of the "Chinese Pharmacopoeia". 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 referred to the quantitative analysis of oleic acid in sodium oleate in the 2020 edition of the "Chinese Pharmacopoeia". The detection results are shown as follows. Figure 4 As shown, 1 is the internal standard, 2 is the peak corresponding to oleic acid, and 3 is the peak corresponding to erucic acid. The calculated contents of oleic acid and erucic acid are 0.14% in total.

[0029] As an indicator that is extremely sensitive to changes in material properties, the relaxation rate plays a key role in evaluating material stability. In this protocol, we used a 0.5T relaxation rate meter to monitor the purified dopamine-polyethylene glycol-modified 3nm ultra-small manganese ferrite nanoparticles. Figure 5 As shown, after a storage period of up to 6 months, the relaxivity of the nanoparticles did not show any significant change. Specific implementation method 6 Combination Figure 1 , Figure 6 , Figure 7In one embodiment of the present invention, the steps of purifying the ligand exchange reaction stock solution containing 20 nm ferrosoferric oxide modified with 6000 Da carboxyl-terminated polyethylene glycol include: S1: Preparation of stock solution: a stock solution of inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives obtained by ligand exchange method, including 20 nm ferroferric oxide modified with 6000 Da carboxyl-terminated polyethylene glycol, ferroferric oxide nanoparticles with residual oleic acid on the surface due to incomplete ligand exchange, free carboxyl-terminated polyethylene glycol, replaced oleic acid and oleate. These impurities are mixed with the product in about 4 L of toluene; S2: Alkane precipitation: 10L petroleum ether was added to 4L stock solution to generate alkane precipitation liquid; S3: Alkane washing: The alkane precipitate was stirred at room temperature and then allowed to stand, the supernatant was removed, and the remaining lower waxy solid-liquid mixture was dried by a vacuum dryer to obtain 40 g of a solid initial product; S4: Acid dissolution: 1.5 L of hydrochloric acid ethanol solution with a pH value of 6.5 was added to the solid primary product to obtain an acid-dissolved product; S5: Ether solvent extraction and phase separation: add 10L of isopropyl ether to the acid-dissolved product, stir and let stand, remove the supernatant organic phase, and obtain the lower layer product; S6: Nanofiltration membrane separation: Select a nanofiltration membrane with a pore size of 10 nm, dissolve the lower layer product with ethanol and add it to the roll nanofiltration equipment, set the operating pressure to 0.1 MPa, set the operating temperature to 35°C, start the cycle, discard the filtrate to remove free carboxyl-terminated polyethylene glycol, and after 10 cycles, the unfiltered material is the purified carboxyl-terminated polyethylene glycol-modified ferrosoferric oxide nanoparticles.

[0031] In this embodiment, after the treatments from S1 to S5, the system to be filtered is converted from 4L toluene solution to 1.5L ethanol solution, and the impurities in the solution do not contain surfactants such as oleic acid and oleate, eliminating the emulsification and agglomeration phenomenon in the nanofiltration process. The electron microscopy of the inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives after purification in this embodiment is as follows: Figure 6 As shown, dynamic light scattering characterization is as follows Figure 7 As shown, the carboxyl-terminated polyethylene glycol-modified ferroferric oxide nanoparticles purified by this method are uniform in size, with a polydispersity index of 0.28 and no obvious agglomeration. The content of free polyethylene glycol derivatives in the product was detected. 2 mL of carboxyl-terminated polyethylene glycol-modified ferroferric oxide nanoparticles were centrifuged in a 10KD ultrafiltration tube at 3000g for 20 minutes and the lower clear liquid was taken. The polyethylene glycol derivatives in the lower clear liquid were detected with reference to the General Rules 3202 of the 2020 edition of the Chinese Pharmacopoeia, and the free polyethylene glycol derivative content was measured to be 0.81%. The residual oleic acid in the product was detected by gas chromatography, and the oleic acid content was 0.25%. Specific implementation method 7 Combination Figure 1 , Figure 8 , Fig. 9 In one embodiment of the present invention, a reaction stock solution is obtained by ligand exchange method, 10 g of 6 nm gold nanoparticles coated with oleylamine are dissolved in 0.5 L chloroform and then in 2 L chloroform solution of 40 g of phosphorylated polyethylene glycol with a number average molecular weight of about 600 Da, and reacted at 35° C. for 12 h. The step of purifying the reaction stock solution comprises: S1: Preparation of stock solution: The 600Da phosphorylated polyethylene glycol-modified 6nm gold nanoparticle stock solution obtained by the ligand exchange method contains phosphorylated polyethylene glycol-modified gold nanoparticles, gold nanoparticles with residual oleylamine on the surface due to incomplete ligand exchange, free phosphorylated polyethylene glycol, and replaced oleylamine. These impurities are mixed with the product in about 2.5L of chloroform.

[0033] S2: Alkane precipitation: 10 L of n-pentane was added to about 2.5 L of the ligand exchange reaction stock solution to generate an alkane precipitation solution; S3: Alkane washing: Stir the alkane precipitate at room temperature and then let it stand, remove the supernatant, and dry the remaining lower waxy solid-liquid mixture in a vacuum dryer. The drying conditions are vacuum degree 0.8 MPa, 30°C and drying for 30 min to obtain about 30 g of solid initial product; S4: Acid dissolution: add 1 L of hydrochloric acid aqueous solution with a pH value of 6.5 to the solid primary product, dissolve it by ultrasonication, and obtain an acid-dissolved product; S5: Ether solvent extraction and phase separation: add 0.5L methyl tert-butyl ether to the acid-dissolved product, stir and let stand, discard the upper organic phase after stratification, repeat this step twice to obtain the lower aqueous phase product; S6: Nanofiltration membrane separation: Select a nanofiltration membrane with a pore size of 5 nm, add the aqueous phase product into the roll nanofiltration equipment, set the operating pressure to 0.2 MPa, set the operating temperature to 30°C, start the circulation, discard the filtrate to remove free polyethylene glycol derivatives, and add ultrapure water in time during the circulation process to keep the circulating liquid in the equipment not less than the minimum circulation volume. After 10 cycles, the nanofiltration membrane separation concentrate is obtained. The concentrate is the 6nm gold nanoparticles modified with phosphorylated polyethylene glycol in the aqueous phase.

[0034] In this example, after the treatments from S1 to S5, the system to be filtered is converted from 2.5L chloroform solution to 1L aqueous solution, and the impurities in the solution do not contain surfactant oleylamine, eliminating the emulsification and agglomeration phenomenon in the nanofiltration process. The electron microscopy of the aqueous phase particles after purification in this example is as follows: Figure 8 As shown, dynamic light scattering characterization is as follows Fig. 9As shown, the water phase particles purified by this method are uniform in size, without obvious agglomeration, and the polydispersity index is 0.26. The content of free polyethylene glycol derivatives in the product was detected. 2 mL of water phase particles were centrifuged in a 10KD ultrafiltration tube at 3000g for 20 minutes, and the lower clear liquid was taken. The polyethylene glycol derivatives in the lower clear liquid were detected with reference to the General Rules 3202 of the 2020 edition of the Chinese Pharmacopoeia, and the free polyethylene glycol derivative content was measured to be 0.9%. Specific implementation method 8 Combination Figure 1 In one embodiment of the present invention, a reaction stock solution is obtained by a ligand exchange method, comprising ultra-small manganese zinc ferrite nanoparticles modified with ethoxybenzene having a surface metal ion to surface ligand number ratio of 3:1. , free ethoxybenzene, ultra-small manganese zinc ferrite nanoparticles with residual oleic acid on the surface due to incomplete ligand exchange, oleic acid, tetrahydrofuran, and oleate. The steps of purifying the inorganic nanoparticle stock solution modified with medium and low molecular weight polyethylene glycol derivatives include: S1: Preparation of stock solution: The reaction stock solution is obtained by ligand exchange method, which contains ultra-small manganese zinc ferrite nanoparticles modified with ethoxybenzene with a surface metal ion to surface ligand number ratio of 3:1. , free ethoxybenzene, ultra-small manganese zinc ferrite nanoparticles with residual oleic acid on the surface due to incomplete ligand exchange, oleic acid, oleate, these impurities were mixed with the product in about 4 L of tetrahydrofuran; S2: Alkane precipitation: 4 L of petroleum ether is added to about 4 L of the ligand exchange reaction stock solution to generate 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 ultra-small manganese zinc ferrite nanoparticles modified with ethoxybenzene ligands and free ethoxybenzene ligands are precipitated from the ligand exchange reaction stock solution; S3: Alkane washing: Stir the alkane sediment at room temperature and then let it stand, remove the supernatant, and dry the remaining waxy solid-liquid mixture to obtain about 40g of a solid initial product. The supernatant discarded in this step contains ultra-small manganese zinc ferrite nanoparticles with residual oleic acid on the surface due to incomplete ligand exchange, partially replaced oleic acid, and an organic solvent, tetrahydrofuran. The impurities in the solid initial product mainly include free ethoxybenzene ligands, oleate, and partially incompletely reacted oleic acid contained in ultra-small manganese zinc ferrite nanoparticles modified with ethoxybenzene ligands; S4: Acid dissolution: 4 L of hydrochloric acid aqueous solution with a pH value of 6.5 is added to the solid primary product to obtain an acid-dissolved product with a concentration of about 10 mg / mL. In this step, a trace amount of hydrochloric acid strips off the partially incompletely reacted oleic acid in the ultra-small manganese zinc ferrite nanoparticles modified with ethoxybenzene ligands, and converts the oleate impurities into the corresponding oleic acid and inorganic salts; S5: Ether solvent extraction and phase separation: add 2L of methyl tert-butyl ether to the acid-dissolved product, stir and then let stand, remove the supernatant, the supernatant is the organic phase solution, and the lower layer product is obtained, which is the aqueous phase. In this step, methyl tert-butyl ether is used to extract and remove oleic acid and oleate, and also extract and remove part of hydrogen chloride. After this step, the lower layer product obtained includes residual impurities mainly including free ethoxybenzene ligands and inorganic salt impurities; S6: Nanofiltration membrane separation: A nanofiltration membrane with a pore size of 3 nm is selected to separate the lower layer product through the nanofiltration membrane, thereby obtaining ultrasmall manganese zinc ferrite nanoparticles modified with ethoxybenzene ligands in which the ratio of the number of surface metal ions to surface ligands in the aqueous phase is 3:1.

[0036] The obtained surface metal ion to surface ligand ratio is 3:1 for the ultrasmall manganese zinc ferrite nanoparticles modified with ethoxybenzene The purity is 95.7%, of which free ethoxybenzene is 3.4% and oleate impurity content is 0.9%.

[0037] Comparative Example 1 Similarly, the reaction stock solution in Implementation 5 is purified. 16L of ether is added as a poor solvent to purify 4L of reaction stock solution by high-speed centrifugation, and centrifuged for 5 minutes under 5000g centrifugal force. The high-speed centrifuge that can achieve a one-time centrifugation of 20L is expensive, so 10mL of stock solution is added to 40mL of ether for high-speed centrifugation purification to compare the effect of this method with this solution. The product after purification in this solution is compared with the product after purification in Implementation 5, as shown in Table 1, wherein the content of free polyethylene glycol derivatives is 6.1%, and the content of oleic acid and erucic acid is 0.58% in total.

[0038] Comparative Example 2 Similarly, the reaction stock solution in Implementation Example 5 was purified directly using a nanofiltration device without treatment. A nanofiltration membrane with a pore size of 3 nm was selected, 4 L of the reaction stock solution was added to the roll-type nanofiltration device, the operating pressure was set to 0.2 MPa, the operating temperature was set to 30°C, the circulation was started, and the filtrate was discarded. During the circulation process, the circulating liquid in the device was kept not less than the minimum circulation volume. The electron microscopy of the aqueous phase particles purified by this method is as follows Fig.10 As shown, it can be seen that the purification method used in Comparative Example 2 failed to complete purification due to serious emulsification during the purification process, resulting in obvious agglomeration of particles. The comparison with the product after purification in Implementation Example 5 is shown in Table 1. The final treatment system in Table 1 is the liquid volume and solvent that need to be treated by the nanofiltration membrane / centrifuge to treat 4L of the reaction stock solution. × represents that the impurity content in the product exceeds the detection limit due to emulsification and agglomeration. The hydrodynamic size of the three measurements is as follows Fig.11 As shown, multiple peaks appeared, which also proved that obvious aggregation occurred.

[0039] Table 1

[0040] It can be seen that the method for purifying inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives provided by the present invention can effectively prevent the emulsification and agglomeration of inorganic nanoparticles in the nanofiltration membrane, improve the utilization efficiency of the nanofiltration membrane equipment, and reduce the corrosion of the nanofiltration membrane equipment by organic solvents. At the same time, the obtained product has a low content of free polyethylene glycol derivatives, a concentrated hydrodynamic size distribution, and good monodispersity.

Claims

1. A method for purifying inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives, characterized in that: The following steps are involved: S1: preparing a stock solution: a stock solution of inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives obtained by a ligand exchange method, comprising inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives of 600-6000Da, free polyethylene glycol derivatives, inorganic nanoparticles with residual long-chain fatty acids and / or fatty amines on the surface due to incomplete ligand exchange, long-chain fatty acids and / or fatty amines, organic solvents, metal organic acid salts and inorganic salt impurities, wherein the organic solvent is one or more of tetrahydrofuran, chloroalkane, toluene, ethanol and N,N-dimethylformamide; S2: Alkane precipitation: adding alkane to the stock solution, the volume ratio of the stock solution to the alkane is in the range of [1:10, 1:1], wherein the alkane is a straight-chain or branched alkane composed of 5-10 carbon atoms, to generate an alkane precipitation liquid; S3: Alkane washing: The alkane precipitate is stirred at room temperature and then allowed to stand, the supernatant is removed, and the remaining waxy solid-liquid mixture at the lower layer is dried to obtain a solid primary product; S4: Acid dissolution: adding a hydrochloric acid solution with a pH value of 5-6.5 to the solid primary product to make the concentration of the solid primary product [10, 100] mg / mL to obtain an acid-dissolved product; S5: ether solvent extraction and phase separation: add an ether solvent to the acid-dissolved product, the volume ratio of the acid-dissolved product to the ether solvent is in the range of [1:5, 2:1], stir and then stand, remove the supernatant, and obtain the 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 method for purifying inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives according to claim 1, characterized in that: In S1, the polyethylene glycol derivatives in the inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives of 600-6000Da are modified with polyethylene glycol to introduce one or more of carboxyl, phosphate, catechol, thiol, hydroxyl, and ethoxybenzene functional groups, and the inorganic nanoparticles 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.

3. The method for purifying inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives according to claim 1, characterized in that: In S3, the remaining lower waxy solid-liquid mixture is dried by using a vacuum dryer, and the drying conditions are a vacuum degree of not less than 0.6 MPa, a temperature of 30° C.-60° C., and a drying time of 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 an alcoholic hydrochloric acid solution.

5. The method for purifying inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives according to claim 1, characterized in that: In S5, the ether solvent is a mixture of one or more of ethyl ether, propyl ether, butyl ether, dichlorodiethyl ether, and anisole.

6. 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 pore size of the nanofiltration membrane is selected to meet the following requirements: when the core size of the inorganic nanoparticles is between 2-5nm, a nanofiltration membrane with a pore size of 2-3nm is selected; when the core size of the inorganic nanoparticles is between 5-10nm, a nanofiltration membrane with a pore size of 3-6nm is selected; when the core size of the inorganic nanoparticles is greater than 10nm, a nanofiltration membrane with a pore size of 8-12nm 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, characterized in that: In S6, the separation of the lower layer product by the nanofiltration membrane is separation of the lower layer product by the nanofiltration membrane of the roll nanofiltration equipment, the pressure is 0.1-0.5MPa, the operating temperature is 15°C-60°C, and the number of cycles is not less than 2 times.

9. A purified product obtained by the method for purifying inorganic nanoparticles modified with medium- and low-molecular-weight polyethylene glycol derivatives as described in any one of claims 1 to 8, characterized in that: S1, preparing a stock solution, a stock solution of inorganic nanoparticles modified with medium and low molecular weight polyethylene glycol derivatives obtained by ligand exchange method, comprising ultra-small manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligands , free dopamine-polyethylene glycol-ethoxybenzene ligand, ultra-small manganese ferrite nanoparticles with residual long-chain fatty acids and / or fatty amines on the surface due to incomplete ligand exchange, long-chain fatty acids and / or fatty amines, organic solvents, metal organic acid salts and inorganic salt impurities, and the purified product obtained after S2-S5 is ultra-small manganese ferrite nanoparticles modified with dopamine-polyethylene glycol-ethoxybenzene ligands of not less than 94.5% , less than 5% free dopamine-polyethylene glycol-ethoxyphenyl ligand, less than 0.5% long chain fatty acids or fatty amines.

10. A purified product obtained by the method for purifying inorganic nanoparticles modified with medium- and low-molecular-weight polyethylene glycol derivatives as described in any one of claims 1 to 8, characterized in that: The S1, prepares a stock solution, wherein the inorganic nanoparticle stock solution modified with medium and low molecular weight polyethylene glycol derivatives obtained by the ligand exchange method comprises ultra-small manganese zinc ferrite nanoparticles modified with ethoxybenzene having a surface metal ion to surface ligand number ratio of 3:

1. , free ethoxybenzene, ultra-small manganese zinc ferrite nanoparticles with residual long-chain fatty acids and / or fatty amines on the surface due to incomplete ligand exchange, long-chain fatty acids and / or fatty amines, organic solvents, metal organic acid salts and inorganic salt impurities, and the purified product obtained after S2-S5 is an ultra-small manganese zinc ferrite nanoparticle modified with ethoxybenzene having a surface metal ion to surface ligand number ratio of 3:1 of not less than 95.5%. , less than 3.5% free ethoxybenzene, less than 1% long-chain fatty acids or fatty amines.

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