Metal organic framework composite adsorbent, preparation method thereof and hemoperfusion device

Abstract

The invention provides a metal organic framework composite adsorbent, a preparation method thereof and a hemoperfusion device, and belongs to the technical field of blood purification adsorption materials. The metal organic framework composite adsorbent provided by the invention is a metal organic framework material-polysulfone material composite sphere, the metal organic framework material has excellent adsorbability to various toxins, and the polysulfone material has good biocompatibility, mechanical strength, processing adaptability and sterilization capability; therefore, the metal organic framework composite adsorbent has good blood compatibility and toxin adsorbability, is less in adsorbent particle falling, and is suitable for the field of whole blood perfusion. The result of the embodiment shows that the metal organic framework composite adsorbent provided by the invention has excellent adsorption performance on p-cresol sulfate, indoleacetic acid, bilirubin, bile acid and endotoxin, and shows excellent blood compatibility.

Description

Technical Field

[0001] The invention relates to the technical field of blood purification adsorption materials, and in particular to a metal organic framework composite adsorbent and a preparation method thereof and a blood perfusion device. Background Art

[0002] Hemoperfusion adsorbents can remove pollutants by non-specific or specific adsorption of poisons, drugs and metabolites, thereby achieving the purpose of purifying the blood. At present, the common adsorption materials used for hemoperfusion adsorbents are activated carbon and resins, etc. These materials can effectively adsorb and remove harmful substances such as toxins, metabolites and immune complexes in the blood, and have a wide range of applications in the fields of kidney disease, liver disease, immune disease, drug overdose, critical illness, etc.

[0003] However, it was found in clinical treatment and scientific research experiments that the above-mentioned adsorbent materials generally have problems such as the adsorption capacity of target toxins and blood compatibility that need to be improved. Taking the adsorption material for uremic hemoperfusion as an example, the adsorption material of existing commercial perfusion products is mainly cross-linked polystyrene macroporous adsorption resin, which has limited adsorption and removal effect on uremic protein-bound toxins; and due to its cross-linking brittleness, the cross-linked polystyrene macroporous adsorption resin is prone to particle shedding, affecting its blood safety. Taking the plasma bilirubin adsorber used for hyperbilirubinemia and hypercholecidemia caused by various diseases as an example, the adsorption resin of existing commercial products is mainly ion exchange resin with positively charged quaternary ammonium salt groups, but its blood compatibility is poor and cannot be used for whole blood perfusion. Therefore, how to effectively improve the blood compatibility of the adsorption material and improve the adsorption performance of the material for uremic protein-bound toxins, bilirubin and bile acid is an important research direction in the field of hemoperfusion adsorbent materials.

[0004] Metal-organic framework, or MOF for short, is a type of porous material formed by self-assembly of organic ligands and metal centers. Metal-organic framework MOF materials, with their regular porous structure and adjustable chemical properties, have good adsorption properties and have high potential value in the field of blood perfusion. However, MOF materials often exist in the form of nano- or micron-sized powder particles, which limits their application in the field of blood perfusion; moreover, the clustering effect of tiny particles of MOF materials will reduce the adsorption performance of the material for the target substance. Therefore, MOF materials and related products for blood perfusion are still rare. Summary of the invention

[0005] The purpose of the present invention is to provide a metal organic framework composite adsorbent and a preparation method thereof and a blood perfusion device. The metal organic framework composite adsorbent provided by the present invention has good blood compatibility and excellent adsorption performance for different toxins.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0007] The present invention provides a metal organic framework composite adsorbent, which is a metal organic framework material-polysulfone material composite ball, and the mass ratio of the metal organic framework material to the polysulfone material in the metal organic framework material-polysulfone material composite ball is (1-10): (10-22).

[0008] Preferably, the metal organic framework material-polysulfone material composite sphere is a spherical or quasi-spherical particle, and the particle size of the metal organic framework material-polysulfone material composite sphere is 0.1-2.5 mm.

[0009] Preferably, the metal organic framework material includes one or more of a calcium-based metal organic framework, a modified derivative of a calcium-based metal organic framework, a zirconium-based metal organic framework and a modified derivative of a zirconium-based metal organic framework.

[0010] Preferably, the modifiers of the calcium-based metal-organic framework-modified derivatives and the zirconium-based metal-organic framework-modified derivatives independently include one or more of polyethyleneimine, diethylenetriamine, triethylenetetramine, tetraethylenepentamine, 1,3-propylenediamine, ethylenediamine, 3-dimethylaminopropylamine, tris(2-aminoethyl)amine, N,N'-di-n-propylethylenediamine, N,N-diethylethylenediamine, N,N-dibutylethylenediamine, N,N-dimethylethylenediamine, tris(3-aminopropyl)amine, 2,2'-diamino-N-methyldiethylamine, 3-diethylaminopropylamine, N'N-bis(3-aminopropyl)methylamine, 1,5-diaminopentane, N,N-diethyldiethylenetriamine, 1,6-hexanediamine and polyethylenepolyamine.

[0011] Preferably, the polysulfone material includes one or more of polysulfone, polyethersulfone, sulfonated polyethersulfone and polyarylsulfone.

[0012] The present invention also provides a method for preparing the metal organic framework composite adsorbent described in the above technical solution, comprising the following steps:

[0013] (1) mixing a good solvent, a polysulfone material, an additive and a metal organic framework material to obtain a blended modified solution;

[0014] (2) dropping the blended modified solution obtained in step (1) into a non-good solvent of the polysulfone material to perform phase separation to obtain a metal organic framework composite adsorbent.

[0015] Preferably, the good solvent in step (1) comprises one or more of N,N-dimethylformamide, N,N-dimethylacetamide and N-methylpyrrolidone.

[0016] Preferably, the additive in step (1) comprises one or more of polyethylene glycol, polyvinyl alcohol, polyvinyl pyrrolidone, water, ethylene glycol, n-propanol, isopropanol, glycerol, ethylene glycol methyl ether and lithium chloride.

[0017] Preferably, the non-good solvent for the polysulfone material in step (2) comprises a mixed solution of water and an organic solvent or water, and the organic solvent comprises one or more of dimethyl sulfoxide, N,N-dimethylacetamide, N,N-dimethylformamide and N-methyl-2-pyrrolidone.

[0018] The present invention also provides a blood perfusion device, wherein the adsorbent of the blood perfusion device is the metal-organic framework composite adsorbent described in the above technical solution or the metal-organic framework composite adsorbent prepared by the preparation method described in the above technical solution.

[0019] The present invention provides a metal organic framework composite adsorbent, which is a metal organic framework material-polysulfone material composite ball, and the mass ratio of the metal organic framework material and the polysulfone material in the metal organic framework material-polysulfone material composite ball is (1-10): (10-22). The metal organic framework composite adsorbent provided by the present invention is a metal organic framework material-polysulfone material composite ball, the metal organic framework material has excellent adsorption to various toxins, and the polysulfone material has good biocompatibility, mechanical strength, processing adaptability and sterilization ability, so that the metal organic framework material-polysulfone material composite ball has good blood compatibility and adsorption to toxins, and the adsorbent particles fall off less, making it suitable for the field of whole blood perfusion. The results of the embodiment show that the metal organic framework composite adsorbent provided by the present invention has excellent adsorption performance for p-cresol sulfate, indoleacetic acid, bilirubin, bile acid and endotoxin, and shows excellent blood compatibility. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 This is an infrared spectrum of the calcium-based metal organic framework prepared in Example 1 of the present invention;

[0021] Figure 2 N2 adsorption-desorption isotherm of the calcium-based metal organic framework prepared in Example 1 of the present invention;

[0022] Figure 3 The pore size distribution curve of the calcium-based metal organic framework prepared in Example 1 of the present invention;

[0023] Figure 4 This is an infrared spectrum of the zirconium-based metal organic framework prepared in Example 2 of the present invention;

[0024] Figure 5 N2 adsorption-desorption isotherm of the zirconium-based metal organic framework prepared in Example 2 of the present invention;

[0025] Figure 6 This is the pore size distribution curve of the zirconium-based metal organic framework prepared in Example 2 of the present invention;

[0026] Figure 7 This is an infrared spectrum of the zirconium-based metal organic framework prepared in Example 3 of the present invention;

[0027] Figure 8 This is the N2 adsorption-desorption isotherm of the zirconium-based metal organic framework powder prepared in Example 3 of the present invention;

[0028] Fig. 9 This is the pore size distribution curve of the zirconium-based metal organic framework powder prepared in Example 3 of the present invention;

[0029] Fig.10 This is a photo of the metal-organic framework composite adsorbent prepared in Example 11 of the present invention;

[0030] Fig.11 This is a photo of the metal-organic framework composite adsorbent prepared in Example 12 of the present invention;

[0031] Fig.12 This is a photo of the metal-organic framework composite adsorbent prepared in Example 13 of the present invention. DETAILED DESCRIPTION

[0032] The invention provides a metal organic framework composite adsorbent, which is a metal organic framework material-polysulfone material composite ball.

[0033] In the present invention, the mass ratio of the metal organic framework material and the polysulfone material in the metal organic framework material-polysulfone material composite ball is (1-10): (10-22). In an embodiment of the present invention, the mass ratio of the metal organic framework material and the polysulfone material can be specifically: 2:21, 1.5:20, 3:20, 1:20, 8:15, 2:22, 10:10 or 3:21. The metal organic framework composite adsorbent provided by the present invention uses the polysulfone material as a carrier to disperse the metal organic framework material therein, thereby solving the problem of decreased adsorption performance caused by agglomeration of the metal organic framework material powder, and can also solve the problem of poor blood compatibility of the metal organic framework material powder, and at the same time can also solve the problem of poor adsorption performance of the polysulfone material for toxins, thereby making the metal organic framework composite adsorbent have better adsorption performance and blood compatibility for toxins. The present invention controls the mass ratio of the metal organic framework material and the polysulfone material within the above range, which can enable the adsorbent to maintain good adsorption, blood compatibility and mechanical properties.

[0034] In the present invention, the metal organic framework material-polysulfone material composite ball is preferably a spherical or quasi-spherical particle, and the particle size of the metal organic framework material-polysulfone material composite ball is preferably 0.1 to 2.5 mm, more preferably 0.8 to 1.4 mm. In an embodiment of the present invention, the particle size of the metal organic framework material-polysulfone material composite ball can be specifically: 0.9 mm, 1.0 mm, 1.2 mm or 1.4 mm. The present invention controls the particle size of the metal organic framework material-polysulfone material composite ball within the above range, which is more conducive to the adsorbent used for blood perfusion device.

[0035] In the present invention, the polysulfone material preferably includes one or more of polysulfone, polyethersulfone, sulfonated polyethersulfone and polyarylsulfone, more preferably polysulfone, polyethersulfone or sulfonated polyethersulfone. The polysulfone material used in the present invention has good blood compatibility.

[0036] In the present invention, the metal organic framework material preferably includes one or more of a calcium-based metal organic framework, a calcium-based metal organic framework modified derivative, a zirconium-based metal organic framework and a zirconium-based metal organic framework modified derivative, more preferably a calcium-based metal organic framework or a calcium-based metal organic framework modified derivative.

[0037] In the present invention, the preparation method of the calcium-based metal organic framework preferably comprises: mixing an organic ligand, a calcium source, a solvent A and a regulator to obtain a precursor solution; and subjecting the precursor solution to a coordination reaction to obtain a calcium-based metal organic framework powder.

[0038] In the present invention, the organic ligand, the calcium source, the solvent A and the regulator are preferably mixed to obtain a precursor solution.

[0039] In the present invention, the organic ligand preferably includes one or more of terephthalic acid, 2-aminoterephthalic acid, isophthalic acid, 2-hydroxyterephthalic acid, 4-hydroxyisophthalic acid, 2,5-dihydroxyterephthalic acid and 2,5-diaminoterephthalic acid, more preferably terephthalic acid, 2-aminoterephthalic acid or isophthalic acid. The present invention uses the above organic ligands to construct a metal organic framework powder with excellent adsorption performance.

[0040] In the present invention, the calcium source preferably includes one or more of calcium chloride, calcium nitrate and calcium carbonate, more preferably calcium chloride. The present invention uses the above calcium source to provide calcium ions, so that the prepared metal organic framework is a calcium-based metal organic framework material.

[0041] In the present invention, the solvent A preferably includes one or more of water, ethanol, methanol, isopropanol and butanol. In an embodiment of the present invention, when the solvent A is a mixture of multiple solvents, the solvent A can be specifically a mixed solvent consisting of ethanol and water, and the mass ratio of the ethanol to water can be specifically 30:20 or 20:40. The present invention uses the above solvents to provide a suitable reaction environment for the coordination reaction.

[0042] In the present invention, the regulator preferably includes one or more of sodium hydroxide, potassium hydroxide, acetylacetone, formic acid, acetic acid and hydrochloric acid, and more preferably sodium hydroxide, potassium hydroxide or hydrochloric acid. The present invention uses the above regulator to adjust the crystal structure, pore size and surface chemical properties of the metal organic framework material, which is more conducive to improving the quality of the metal organic framework material.

[0043] In the present invention, the molar ratio of the calcium source, the organic ligand and the regulator is preferably 1:(0.2-3):(0.01-50), more preferably 1:1:(1-5). The present invention controls the molar ratio of the calcium source, the organic ligand and the regulator within the above range, which can adjust the crystallinity, molecular orientation and structural morphology of the metal organic framework material, thereby improving the adsorption performance of the metal organic framework material.

[0044] In the present invention, the mass ratio of the organic ligand to the solvent A is preferably 1:(1-100), more preferably 1:(20-80). The present invention controls the mass ratio of the organic ligand to the solvent A within the above range, which can promote the coordination reaction to proceed fully.

[0045] The present invention has no particular limitation on the method for mixing the organic ligand, the calcium source, the solvent A and the regulator, as long as each component can be completely dissolved in the solvent.

[0046] After obtaining the precursor solution, the present invention preferably subjects the precursor solution to a coordination reaction to obtain a metal organic framework powder.

[0047] In the present invention, the temperature of the coordination reaction can be 40 to 105°C, or 80 to 95°C; in an embodiment of the present invention, the temperature of the coordination reaction can be specifically: 80°C, 90°C or 95°C. In the present invention, the time of the coordination reaction can be 3 to 48 hours, or 12 to 24 hours. In the present invention, the coordination reaction is preferably carried out under normal pressure. The present invention controls the temperature and time of the coordination reaction within the above range, which is more conducive to the full progress of the coordination reaction.

[0048] The present invention preferably washes and dries the solid product obtained by the coordination reaction to obtain a calcium-based metal organic framework powder. The present invention has no special restrictions on the washing and drying operation methods, and conventional washing and drying methods can be used to fully remove impurities and moisture in the solid product.

[0049] In the present invention, the method for preparing the zirconium-based metal organic framework preferably comprises: mixing an organic ligand, a zirconium source, a solvent A and a regulator to obtain a precursor solution; and subjecting the precursor solution to a coordination reaction to obtain a zirconium-based metal organic framework powder.

[0050] In the present invention, the zirconium source preferably includes one or more of zirconium oxychloride octahydrate, zirconium chloride, zirconium nitrate, zirconium sulfate, zirconium acetylacetonate and zirconium n-propoxide, and more preferably zirconium oxychloride octahydrate, zirconium chloride or zirconium nitrate. The present invention uses the above zirconium sources to provide zirconium ions for the metal organic framework material.

[0051] In the present invention, the method for preparing the zirconium-based metal-organic framework is different from the method for preparing the calcium-based metal-organic framework described in the above technical solution in that the calcium source is replaced by a zirconium source, and the remaining operations and parameters are the same as those of the method for preparing the calcium-based metal-organic framework, which will not be repeated here.

[0052] In the present invention, the preparation method of the calcium-based metal organic framework modified derivative preferably comprises:

[0053] Mixing calcium-based metal organic framework powder, solvent B and graft anchor agent, and performing a first stirring reaction to obtain a metal organic framework material containing a graft anchor agent;

[0054] The metal organic framework material containing the grafted anchoring agent, the modifier and the solvent C are mixed and subjected to a second stirring reaction to obtain a calcium-based metal organic framework modified derivative.

[0055] In the present invention, the calcium-based metal organic framework powder, solvent B and a graft anchoring agent are preferably mixed to carry out a first stirring reaction to obtain a metal organic framework material containing a graft anchoring agent.

[0056] In the present invention, the solvent B preferably includes one or more of water, ethanol and methanol. The present invention utilizes the solvent B to provide a suitable reaction environment for the reaction.

[0057] In the present invention, the graft anchoring agent preferably includes one or more of tannic acid, dopamine, 3-bromopropionic acid, 3-chloropropionic acid and 2-chloropropionic acid, and more preferably tannic acid, dopamine or 3-bromopropionic acid. The present invention is more conducive to the grafting of the modifier onto the metal organic framework material by adding the graft anchoring agent.

[0058] The present invention has no particular limitation on the method for mixing the calcium-based metal organic framework powder, solvent B and graft anchoring agent, as long as the above components are fully dispersed in solvent B.

[0059] In the present invention, the pH value of the system obtained by mixing the calcium-based metal organic framework powder, solvent B and graft anchor is preferably 5 to 10, more preferably 6.5 to 8. The present invention does not specifically limit the reagent for adjusting the pH value, and a conventional adjusting reagent can be used to make the pH value of the system reach the above range. The present invention controls the pH value of the system within the above range, which is more conducive to promoting the full reaction of the metal organic framework powder and the graft anchor.

[0060] In the present invention, the temperature of the first stirring reaction can be 50-90°C, or 50-80°C; in an embodiment of the present invention, the temperature of the first stirring reaction can be specifically 50°C, 60°C, 75°C or 80°C. In the present invention, the time of the first stirring reaction can be 6-48h; in an embodiment of the present invention, the time of the first stirring reaction can be specifically 6h, 12h, 24h, 32h or 48h. The present invention stirs under the above conditions to allow the metal organic framework powder and the grafting anchor to fully react.

[0061] In the present invention, the solid obtained after the first stirring reaction is preferably washed to obtain a metal organic framework material containing a grafted anchoring agent. The present invention has no particular limitation on the washing method, as long as the impurities in the solid obtained by the reaction can be removed.

[0062] After obtaining the metal organic framework material containing the grafted anchor agent, the present invention preferably mixes the metal organic framework material containing the grafted anchor agent, the modifier and the solvent C, and performs a second stirring reaction to obtain a calcium-based metal organic framework modified derivative.

[0063] In the present invention, the modifier preferably includes one or more of polyethyleneimine, diethylenetriamine, triethylenetetramine, tetraethylenepentamine, 1,3-propylenediamine, ethylenediamine, 3-dimethylaminopropylamine, tris(2-aminoethyl)amine, N,N'-di-n-propylethylenediamine, N,N-diethylethylenediamine, N,N-dibutylethylenediamine, N,N-dimethylethylenediamine, tris(3-aminopropyl)amine, 2,2'-diamino-N-methyldiethylamine, 3-diethylaminopropylamine, N'N-bis(3-aminopropyl)methylamine, 1,5-diaminopentane, N,N-diethyldiethylenetriamine, 1,6-hexanediamine and polyethylenepolyamine, more preferably polyethyleneimine, diethylenetriamine, triethylenetetramine, tetraethylenepentamine, 1,3-propylenediamine, ethylenediamine or 3-dimethylaminopropylamine. The present invention adopts the above-mentioned modifier to introduce amine groups into the metal organic framework, which is more conducive to improving the adsorption performance of the adsorbent.

[0064] In the present invention, the solvent C preferably includes one or more of water, ethanol and methanol. The present invention uses the solvent C to provide a suitable reaction environment for the reaction.

[0065] In the present invention, the mass ratio of the metal organic framework powder, solvent B, grafting anchor, modifier and solvent C is preferably 1: (3-100): (0.1-3): (0.1-5): (5-100), more preferably 1: (5-80): (1-3): (1-5): (10-500). The present invention limits the amount of each component to the above range, so that the modifier can be fully grafted onto the metal organic framework material.

[0066] The present invention has no special limitation on the method of mixing the metal organic framework material containing the graft anchor, the modifier and the solvent C, as long as the components can be mixed evenly.

[0067] In the present invention, the temperature of the second stirring reaction can be 40 to 90°C, or 40 to 80°C; in an embodiment of the present invention, the temperature of the second stirring reaction can be specifically 40°C, 50°C, 60°C, 70°C or 80°C. In the present invention, the time of the second stirring reaction can be 6 to 48h; in an embodiment of the present invention, the time of the second stirring reaction can be specifically 6h, 12h, 24h or 48h. The present invention stirs under the above conditions to allow the metal organic framework powder containing the grafted anchor agent and the modifier to fully react.

[0068] In the present invention, the product obtained by the second stirring reaction is preferably washed and dried in sequence to obtain a calcium-based metal organic framework modified derivative. The present invention has no particular limitation on the operation method of the washing and drying, and conventional washing and drying can be used to fully remove impurities and moisture in the calcium-based metal organic framework modified derivative.

[0069] In the present invention, the method for preparing the zirconium-based metal organic framework modified derivative preferably comprises:

[0070] The zirconium-based metal organic framework powder, solvent B and a graft anchor agent are mixed and subjected to a first stirring reaction to obtain a metal organic framework material containing a graft anchor agent;

[0071] The metal organic framework material containing the grafted anchoring agent, the modifier and the solvent C are mixed and subjected to a second stirring reaction to obtain a zirconium-based metal organic framework modified derivative.

[0072] In the present invention, the preparation method of the zirconium-based metal-organic framework modified derivative is different from the preparation method of the calcium-based metal-organic framework modified derivative described in the above technical scheme in that the zirconium-based metal-organic framework powder is used to replace the calcium-based metal-organic framework powder, and the remaining steps are the same as the preparation method of the calcium-based metal-organic framework modified derivative described in the above technical scheme, which will not be repeated here.

[0073] The metal organic framework composite adsorbent provided by the present invention is a metal organic framework material-polysulfone material composite ball. The metal organic framework material has excellent adsorption to various toxins, and the polysulfone material has good biocompatibility, mechanical strength, processing adaptability and sterilization ability, so that the metal organic framework composite adsorbent has good blood compatibility and adsorption to toxins, and the adsorbent particles fall off less.

[0074] The present invention also provides a method for preparing the metal organic framework composite adsorbent described in the above technical solution, comprising the following steps:

[0075] (1) mixing a good solvent, a polysulfone material, an additive and a metal organic framework material to obtain a blended modified solution;

[0076] (2) dropping the blended modified solution obtained in step (1) into a non-good solvent of the polysulfone material to perform phase separation to obtain a metal organic framework composite adsorbent.

[0077] The invention mixes a good solvent, a polysulfone material, an additive and a metal organic framework material to obtain a blended modified solution.

[0078] In the present invention, the good solvent preferably includes one or more of N,N-dimethylformamide, N,N-dimethylacetamide and N-methylpyrrolidone. The good solvent used in the present invention has good solubility for polysulfone materials.

[0079] In the present invention, the additive preferably includes one or more of polyethylene glycol, polyvinyl alcohol, polyvinyl pyrrolidone, water, ethylene glycol, n-propanol, isopropanol, glycerol, ethylene glycol methyl ether and lithium chloride, and more preferably includes polyethylene glycol, polyvinyl alcohol, polyvinyl pyrrolidone, water or ethylene glycol. The present invention can stabilize the mixed solution by the additive.

[0080] In the present invention, the metal organic framework material preferably includes one or more of a calcium-based metal organic framework, a modified derivative of a calcium-based metal organic framework, a zirconium-based metal organic framework, and a modified derivative of a zirconium-based metal organic framework.

[0081] In the present invention, the mass ratio of the good solvent, the polysulfone material, the additive and the metal organic framework material is preferably 100:(10-35):(0-5):(0.01-10), and more preferably 100:(15-30):(1-4):(1-8). The present invention controls the amount of each component within the above range, which can control the exchange rate between the solvent and the poor solvent, thereby affecting the structure and characteristics of the metal organic framework composite adsorbent porous membrane, so that the metal organic framework composite adsorbent has good adsorption.

[0082] In the present invention, the method for mixing the good solvent, polysulfone material, additive and metal organic framework material is preferably: dissolving the polysulfone material and additive in the good solvent, adding the metal organic framework material to the obtained solution, stirring and mixing evenly, and then standing to remove bubbles to obtain a blended modified solution.

[0083] After obtaining the blended modified solution, the present invention drips the blended modified solution into a non-good solvent of a polysulfone material to perform phase separation to obtain a metal organic framework composite adsorbent.

[0084] In the present invention, the non-good solvent preferably includes a mixed solution of water and an organic solvent or water, and the organic solvent preferably includes one or more of dimethyl sulfoxide, N,N-dimethylacetamide, N,N-dimethylformamide and N-methyl-2-pyrrolidone. In the present invention, when the non-good solvent is a mixed solution of water and an organic solvent, the volume ratio of water to organic solvent is preferably 1: (0-1), more preferably 1: (0.05-0.2).

[0085] When the present invention adopts the above solvent, it is a non-solvent solution of polysulfone material, and can cause non-solvent induced phase separation when mixed with the blending modification liquid to form metal organic framework material-polysulfone material composite balls.

[0086] In the present invention, the method of dripping the blended modified solution into a non-good solvent of the polysulfone material is preferably microfluidic injection. The present invention can form droplets of the blended modified solution in the air through microfluidic injection, and drip into the non-good solvent for phase conversion to form microspheres of uniform size. The present invention does not specifically limit the device of the microfluidic injection, and a conventional microfluidic syringe can be used. In an embodiment of the present invention, the microfluidic syringe can make the particle size of the metal organic framework material-polysulfone material composite sphere reach 0.1 to 2.5 mm.

[0087] The preparation method provided by the invention is simple and easy to operate, and can obtain metal organic framework material-polysulfone material composite balls with uniform particle size distribution, namely, metal organic framework composite adsorbent.

[0088] The present invention also provides a blood perfusion device, wherein the adsorbent of the blood perfusion device is the metal-organic framework composite adsorbent described in the above technical solution or the metal-organic framework composite adsorbent prepared by the preparation method described in the above technical solution.

[0089] The present invention has no special limitation on the model of the blood perfusion device, and any conventional blood perfusion device can be used. The metal organic framework composite adsorbent provided by the present invention can be used to replace the adsorbent in the conventional blood perfusion device because of its excellent mechanical stability, blood compatibility and good adsorption of toxins. It has excellent adsorption performance for bilirubin, bile acid and endotoxin, and shows excellent blood compatibility, and is suitable for the field of whole blood perfusion.

[0090] The technical solutions in the present invention will be described clearly and completely below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0091] Example 1

[0092] A preparation method of a calcium-based metal organic framework comprises the following steps: dissolving terephthalic acid in water, and then sequentially adding sodium hydroxide and calcium nitrate, and mixing them evenly to obtain a precursor solution; heating the precursor solution at 95° C. and stirring the reaction for 12 hours under normal pressure to perform a coordination reaction; washing and drying the solid obtained by the reaction to obtain a calcium-based metal organic framework powder; wherein the amount of calcium nitrate, terephthalic acid and sodium hydroxide is 1:1:2.2; and the mass ratio of terephthalic acid to water is 1:15.

[0093] The calcium-based metal organic framework powder prepared in this example is white powder, and its infrared spectrum is as follows: Figure 1 As shown, from Figure 1 As can be seen in 624cm -1 The characteristic peak of Ca-O bond appears at 1500~1700cm -1 The characteristic peak of carbonyl group appears in the range of 1500~1300cm -1 The characteristic peak of carboxyl group appears in the range.

[0094] The N2 adsorption-desorption isotherm of the calcium-based metal organic framework powder prepared in this example is as follows: Figure 2 The pore size distribution curve is shown in Figure 3 The specific surface area of ​​the zirconium-based metal organic framework powder prepared in this embodiment is 25.9 m 2 / g, and the total pore volume is 0.08cm 3 / g, and the average pore size is 12.06nm.

[0095] Example 2

[0096] A method for preparing a zirconium-based metal organic framework is:

[0097] The terephthalic acid is dissolved in ethanol, and then water, acetic acid and zirconium chloride are added and mixed evenly to obtain a precursor solution; under normal pressure, the precursor solution is heated and stirred at 80° C. for 12 hours to perform a coordination reaction; the solid obtained by the reaction is washed, purified and dried to obtain a zirconium-based metal organic framework powder;

[0098] The molar ratio of zirconium chloride, terephthalic acid and acetic acid is 1:1:1; the mass ratio of terephthalic acid, ethanol and water is 1:30:20.

[0099] The zirconium-based metal organic framework powder prepared in this example is white powder, and its infrared spectrum is as follows: Figure 4 As shown, from Figure 4 It can be seen that at 1509 and 1573cm -1 、1680cm -1 The characteristic peaks of the vibration of the C=C bond of the benzene ring and the carbonyl group in terephthalic acid appeared. In addition, at 565cm -1 A characteristic peak belonging to Zr-O appears at , which proves that the zirconium-based metal organic framework powder was successfully prepared in this example.

[0100] The N2 adsorption-desorption isotherm of the Zr-MOF powder prepared in this example is as follows: Figure 5 The pore size distribution curve is shown in Figure 6 The specific surface area of ​​the zirconium-based metal organic framework powder prepared in this embodiment is 1176 m 2 / g, with a total pore volume of 0.49 cm 3 / g, and the average pore size is 1.69nm.

[0101] Example 3

[0102] A method for preparing a zirconium-based metal organic framework comprises: dissolving 2-aminoterephthalic acid in ethanol, adding water, acetic acid, and zirconium oxychloride octahydrate, and mixing them evenly to obtain a precursor solution; heating the precursor solution at 90° C. and stirring the mixture for reaction for 24 hours under normal pressure; after the reaction is completed, washing and drying the obtained solid to obtain a zirconium-based metal organic framework powder;

[0103] The molar ratio of zirconium oxychloride octahydrate, 2-aminoterephthalic acid and acetic acid is 1:1:2; the mass ratio of 2-aminoterephthalic acid, ethanol and water is 1:20:40.

[0104] The zirconium-based metal organic framework powder prepared in this example is a light brown powder, and its infrared spectrum is as follows: Figure 7 As shown, from Figure 7 It can be seen that 3419cm -1 The broad peak at 1257 cm-1 is the overlap of the characteristic peaks of NH and OH. -1 The characteristic peak is attributed to CN; at 1568cm -1 、1427cm -1 and 1387cm -1 Asymmetric vibration peaks and symmetric vibration peaks attributed to carboxylate anions appear respectively.

[0105] The N2 adsorption-desorption isotherm of the Zr-MOF powder prepared in this example is as follows: Figure 8 The pore size distribution curve is shown in Fig. 9 The specific surface area of ​​the zirconium-based metal organic framework powder prepared in this embodiment is 1293m 2 / g, with a total pore volume of 0.60 cm 3 / g, and the average pore size is 1.85nm.

[0106] Example 4

[0107] A method for preparing a calcium-based metal-organic framework modified derivative comprises dispersing 10 g of the calcium-based metal-organic framework powder prepared in Example 1 in 500 g of water, adding 5 g of tannic acid, adjusting the pH to 6.5, stirring and reacting at 50° C. for 24 h, washing and purifying to obtain a calcium-based metal-organic framework material containing a grafted anchor; dissolving 20 g of polyethyleneimine (average molecular weight of 300) in 500 g of water, adding the calcium-based metal-organic framework material containing a grafted anchor, stirring and dispersing evenly, stirring and reacting at 60° C. for 24 h, washing and drying to obtain a calcium-based metal-organic framework modified derivative powder; wherein the mass ratio of the metal-organic framework powder, solvent B, grafted anchor, modifier and solvent C is 1:50:0.5:2:50.

[0108] Example 5

[0109] A preparation method for a calcium-based metal-organic framework modified derivative comprises the following steps: dispersing 10 g of the calcium-based metal-organic framework powder prepared in Example 1 in 400 g of water, adding 1 g of dopamine, adjusting the pH to 8.0, stirring and reacting at 45° C. for 12 h, washing and purifying, obtaining a calcium-based metal-organic framework material containing a grafted anchoring agent, and setting aside for use; dissolving 10 g of triethylenetetramine in 200 g of water, adding the calcium-based metal-organic framework material containing a grafted anchoring agent, stirring and dispersing uniformly, stirring and reacting at 80° C. for 24 h, washing and purifying, and drying, obtaining a calcium-based metal-organic framework modified derivative powder; wherein the mass ratio of the metal-organic framework powder, solvent B, grafted anchoring agent, modifier, and solvent C is 1:40:0.1:0.1:20.

[0110] Example 6

[0111] A method for preparing a calcium-based metal-organic framework modified derivative comprises: dispersing 10 g of the calcium-based metal-organic framework powder prepared in Example 1 in 50 g of water, adding 20 g of 3-chloropropionic acid, stirring and reacting at 80° C. for 6 h without adjusting the pH, washing and purifying to obtain a calcium-based metal-organic framework material containing a grafted anchoring agent, and setting aside for use; dissolving 25 g of tris(2-aminoethyl)amine in 300 g of ethanol, adding the calcium-based metal-organic framework material containing a grafted anchoring agent, stirring and dispersing evenly, stirring and reacting at 70° C. for 12 h, washing and purifying, and drying to obtain a calcium-based metal-organic framework modified derivative powder; wherein the mass ratio of the metal-organic framework powder, solvent B, grafted anchoring agent, modifier and solvent C is 1:5:2:2.5:30.

[0112] Example 7

[0113] A method for preparing a zirconium-based metal-organic framework modified derivative comprises: dispersing 10 g of the zirconium-based metal-organic framework powder prepared in Example 2 in 100 g of water, adding 5 g of dopamine, adjusting the pH to 8.0, stirring and reacting at 60° C. for 48 h, washing and purifying, obtaining a zirconium-based metal-organic framework material containing a grafted anchoring agent for standby use; dissolving 10 g of 3-dimethylaminopropylamine in 200 g of water, adding the zirconium-based metal-organic framework material containing a grafted anchoring agent, stirring and dispersing evenly, stirring and reacting at 70° C. for 48 h, washing and purifying, and drying to obtain a zirconium-based metal-organic framework modified derivative powder; wherein the mass ratio of the metal-organic framework powder, solvent B, grafted anchoring agent, modifier and solvent C is 1:10:0.5:1:20.

[0114] Example 8

[0115] A method for preparing a zirconium-based metal-organic framework modified derivative is as follows: dispersing 10 g of the zirconium-based metal-organic framework powder prepared in Example 2 in 1000 g of water, adding 30 g of 3-bromopropionic acid, stirring and reacting at 50° C. for 32 hours without adjusting the pH, washing and purifying to obtain a zirconium-based metal-organic framework material containing a grafted anchor, and setting aside; dissolving 30 g of polyethyleneimine (average molecular weight of 300) in 600 g of water, adding the zirconium-based metal-organic framework material containing a grafted anchor, stirring and dispersing evenly, stirring and reacting at 50° C. for 6 hours, washing and purifying, and drying to obtain a zirconium-based metal-organic framework modified derivative powder; wherein the mass ratio of the metal-organic framework powder, solvent B, grafted anchor, modifier and solvent C is 1:100:3:3:60.

[0116] Example 9

[0117] A method for preparing a calcium-based metal-organic framework modified derivative comprises: dispersing 10 g of the calcium-based metal-organic framework powder prepared in Example 1 in 100 g of water, adding 20 g of 3-chloropropionic acid, stirring and reacting at 75° C. for 24 h without adjusting the pH, washing and purifying to obtain a calcium-based metal-organic framework material containing a grafted anchoring agent, and setting aside for use; dissolving 10 g of 1,6-hexanediamine in 300 g of ethanol, adding the calcium-based metal-organic framework material containing a grafted anchoring agent, stirring and dispersing evenly, stirring and reacting at 60° C. for 48 h, washing and purifying, and drying to obtain a calcium-based metal-organic framework modified derivative powder; wherein the mass ratio of the metal-organic framework powder, solvent B, grafted anchoring agent, modifier and solvent C is 1:10:2:1:30.

[0118] Example 10

[0119] A method for preparing a zirconium-based metal-organic framework modified derivative: 10g of the zirconium-based metal-organic framework powder prepared in Example 3 is dispersed in 500g of water, 3g of tannic acid is added, the pH is adjusted to 6.5, and the mixture is stirred and reacted at 60°C for 24h, washed and purified to obtain a zirconium-based metal-organic framework material containing a grafted anchoring agent for standby use; 15g of polyethyleneimine (average molecular weight of 600) is dissolved in 500g of water, and the zirconium-based metal-organic framework material containing a grafted anchoring agent is added, stirred and dispersed evenly, stirred and reacted at 70°C for 24h, washed and purified, and dried to obtain a zirconium-based metal-organic framework modified derivative powder; wherein the mass ratio of the metal-organic framework powder, solvent B, grafted anchoring agent, modifier and solvent C is 1:50:0.3:1.5:50.

[0120] Embodiment 11

[0121] A metal organic framework composite adsorbent, the metal organic framework composite adsorbent is a metal organic framework material-polysulfone material composite ball, the metal organic framework material in the metal organic framework material-polysulfone material composite ball is a calcium-based metal organic framework modified derivative, the polysulfone material is polyethersulfone, and the mass ratio of the metal organic framework material to the polysulfone material is 2:21;

[0122] The preparation method of the above metal organic framework composite adsorbent is:

[0123] (1) 21 g of polyethersulfone, 1.2 g of polyvinylpyrrolidone, and 100 g of N,N-dimethylacetamide were mixed, and after stirring and dissolving completely, 2 g of the calcium-based metal organic framework modified derivative powder prepared in Example 4 was added, and the mixture was stirred and dispersed evenly at 40° C., and allowed to stand or vacuum degassed to obtain a blended modified solution; wherein the mass ratio of the good solvent, the polysulfone material, the additive, and the metal organic framework material was 100:21:1.2:2;

[0124] (2) The blended modified solution obtained in step (1) is subjected to a non-solvent induced phase separation method, i.e., a metering pump is used to extrude the blended modified solution through the inner hole of a needle to form droplets in the air, and the droplets are dropped into water for phase conversion to form microspheres of uniform size. After washing and drying, a metal organic framework composite adsorbent is obtained.

[0125] The photo of the metal organic framework composite adsorbent prepared in this example is shown in Fig.10 As shown. According to the test, the particle size of the metal organic framework composite adsorbent prepared in this embodiment is about 1.2 mm.

[0126] Example 12

[0127] A metal organic framework composite adsorbent, the metal organic framework composite adsorbent is a metal organic framework material-polysulfone material composite ball, the metal organic framework material in the metal organic framework material-polysulfone material composite ball is a calcium-based metal organic framework modified derivative, the polysulfone material is polyethersulfone, and the mass ratio of the metal organic framework material to the polysulfone material is 1.5:20;

[0128] The preparation method of the above metal organic framework composite adsorbent is:

[0129] (1) 20 g of polyethersulfone was mixed with 90 g of N,N-dimethylacetamide, 1.5 g of polyvinylpyrrolidone and 10 g of N,N-dimethylformamide, and after stirring and dissolving completely, 1.5 g of the calcium-based metal organic framework modified derivative powder prepared in Example 5 was added, and the mixture was stirred and dispersed evenly at 30° C., and allowed to stand or be vacuum degassed to obtain a blended modified solution; wherein the mass ratio of the good solvent, the polysulfone material, the additive and the metal organic framework material was 100:20:1.5:1.5;

[0130] (2) The blended modified solution obtained in step (1) is subjected to a non-solvent induced phase separation method, i.e., a metering pump is used to extrude the blended modified solution through the inner hole of a needle to form droplets in the air, and the droplets are dropped into water for phase conversion to form microspheres of uniform size. After washing and drying, a metal organic framework composite adsorbent is obtained.

[0131] The photo of the metal organic framework composite adsorbent prepared in this example is shown in Fig.11 As shown. According to the test, the particle size of the metal organic framework composite adsorbent prepared in this embodiment is about 1.0 mm.

[0132] Embodiment 13

[0133] A metal organic framework composite adsorbent, the metal organic framework composite adsorbent is a metal organic framework material-polysulfone material composite ball, the metal organic framework material in the metal organic framework material-polysulfone material composite ball is a calcium-based metal organic framework modified derivative, the polysulfone material is polysulfone, and the mass ratio of the metal organic framework material to the polysulfone material is 3:20;

[0134] The preparation method of the above metal organic framework composite adsorbent is:

[0135] (1) 20 g of polysulfone was mixed with 100 g of N, N-dimethylacetamide and 1.2 g of polyvinyl pyrrolidone, and after stirring and dissolving completely, 3 g of the calcium-based metal organic framework modified derivative powder prepared in Example 6 was added, and the mixture was stirred and dispersed evenly at 20° C., and allowed to stand or vacuum degas to obtain a blended modified solution; wherein the mass ratio of the good solvent, the polysulfone material, the additive and the metal organic framework material was 100:20:1.2:3;

[0136] (2) The blended modified solution obtained in step (1) is subjected to a non-solvent induced phase separation method, i.e., a metering pump is used to extrude the blended modified solution through the inner hole of a needle to form droplets in the air, which are then dropped into water for phase conversion to form microspheres of uniform size, which are then washed and dried to obtain a metal organic framework composite adsorbent.

[0137] The photo of the metal organic framework composite adsorbent prepared in this example is shown in Fig.12 As shown. According to the test, the particle size of the metal organic framework composite adsorbent prepared in this embodiment is about 1.4 mm.

[0138] Embodiment 14

[0139] A metal organic framework composite adsorbent, the metal organic framework composite adsorbent is a metal organic framework material-polysulfone material composite ball, the metal organic framework material in the metal organic framework material-polysulfone material composite ball is a zirconium-based metal organic framework modified derivative, the polysulfone material is polyethersulfone, and the mass ratio of the metal organic framework material to the polysulfone material is 1:20;

[0140] The preparation method of the above metal organic framework composite adsorbent is:

[0141] (1) 20 g of polyethersulfone, 1.5 g of polyvinylpyrrolidone, and 100 g of N,N-dimethylacetamide were mixed, and after stirring and dissolving completely, 1 g of the zirconium-based metal organic framework modified derivative powder prepared in Example 7 was added, and the mixture was stirred and dispersed evenly at 50° C., and allowed to stand or vacuum degas to obtain a blended modified solution; wherein the mass ratio of the good solvent, the polysulfone material, the additive, and the metal organic framework material was 100:20:1.5:1;

[0142] (2) The blended modified solution obtained in step (1) is subjected to a non-solvent induced phase separation method, i.e., a metering pump is used to extrude the blended modified solution through the inner hole of a needle to form droplets in the air, which are then dropped into water for phase conversion to form microspheres of uniform size, which are then purified to obtain a metal organic framework composite adsorbent.

[0143] The particle size of the metal organic framework composite adsorbent prepared in this example is about 1.2 mm.

[0144] Embodiment 15

[0145] A metal organic framework composite adsorbent, the metal organic framework composite adsorbent is a metal organic framework material-polysulfone material composite ball, the metal organic framework material in the metal organic framework material-polysulfone material composite ball is a zirconium-based metal organic framework modified derivative, the polysulfone material is polyethersulfone, and the mass ratio of the metal organic framework material to the polysulfone material is 8:15;

[0146] The preparation method of the above metal organic framework composite adsorbent is:

[0147] (1) 15 g of polyethersulfone and 100 g of N,N-dimethylacetamide were mixed, and after stirring and dissolving completely, 8 g of the zirconium-based metal organic framework modified derivative powder prepared in Example 8 was added, and the mixture was stirred and dispersed evenly at 30° C., and allowed to stand or vacuum degassed to obtain a blended modified solution; wherein the mass ratio of the good solvent, the polysulfone material, and the metal organic framework material was 100:15:1.5;

[0148] (2) The blended modified solution obtained in step (1) is subjected to a non-solvent induced phase separation method, i.e., a metering pump is used to extrude the blended modified solution through the inner hole of a needle to form droplets in the air, and the droplets are dropped into water for phase conversion to form microspheres of uniform size. After washing and drying, a metal organic framework composite adsorbent is obtained.

[0149] The particle size of the metal organic framework composite adsorbent prepared in this example is about 0.9 mm.

[0150] Example 16

[0151] A metal organic framework composite adsorbent, the metal organic framework composite adsorbent is a metal organic framework material-polysulfone material composite ball, the metal organic framework material in the metal organic framework material-polysulfone material composite ball is a calcium-based metal organic framework modified derivative, the polysulfone material is polyethersulfone, and the mass ratio of the metal organic framework material to the polysulfone material is 2:22;

[0152] The preparation method of the above metal organic framework composite adsorbent is:

[0153] (1) 22 g of polyethersulfone, 1 g of polyvinylpyrrolidone, and 100 g of N,N-dimethylacetamide were mixed, and after stirring and dissolving completely, 2 g of the calcium-based metal organic framework modified derivative powder prepared in Example 9 was added, and the mixture was stirred and dispersed evenly at 50° C., and allowed to stand or vacuum degassed to obtain a blended modified solution; wherein the mass ratio of the good solvent, the polysulfone material, the additive, and the metal organic framework material was 100:22:1:2;

[0154] (2) The blended modified solution obtained in step (1) is subjected to a non-solvent induced phase separation method, i.e., a metering pump is used to extrude the blended modified solution through the inner hole of a needle to form droplets in the air, and the droplets are dropped into a mixed solution of water and N-methyl-2-pyrrolidone (the water ratio is 90 wt%) to undergo phase conversion to form microspheres of uniform size. After washing and drying, a metal organic framework composite adsorbent is obtained.

[0155] The particle size of the metal organic framework composite adsorbent prepared in this example is about 1.2 mm.

[0156] Embodiment 17

[0157] A metal organic framework composite adsorbent, the metal organic framework composite adsorbent is a metal organic framework material-polysulfone material composite ball, the metal organic framework material in the metal organic framework material-polysulfone material composite ball is a zirconium-based metal organic framework modified derivative, the polysulfone material is polyethersulfone, and the mass ratio of the metal organic framework material to the polysulfone material is 10:10;

[0158] The preparation method of the above metal organic framework composite adsorbent is:

[0159] (1) 10 g of polysulfone, 2 g of sulfonated polyethersulfone, 90 g of N,N-dimethylacetamide, 10 g of N-methylpyrrolidone, and 3 g of polyethylene glycol were mixed, and after stirring and dissolving completely, 10 g of the zirconium-based metal organic framework modified derivative powder prepared in Example 10 was added, and the mixture was stirred and dispersed evenly at 45° C., and allowed to stand or vacuum degassed to obtain a blended modified solution; wherein the mass ratio of the good solvent, the polysulfone material, the additive, and the metal organic framework material was 100:10:2:10;

[0160] (2) The blended modified solution obtained in step (1) is subjected to a non-solvent induced phase separation method, i.e., a metering pump is used to extrude the blended modified solution through the inner hole of a needle to form droplets in the air, which are then dropped into water for phase conversion to form microspheres of uniform size, which are then washed and dried to obtain a metal organic framework composite adsorbent.

[0161] The particle size of the metal organic framework composite adsorbent prepared in this example is about 0.6 mm.

[0162] Embodiment 18

[0163] A metal organic framework composite adsorbent, the metal organic framework composite adsorbent is a metal organic framework material-polysulfone material composite ball, the metal organic framework material in the metal organic framework material-polysulfone material composite ball is a zirconium-based metal organic framework, the polysulfone material is polyethersulfone, and the mass ratio of the metal organic framework material to the polysulfone material is 3:21;

[0164] The preparation method of the above metal organic framework composite adsorbent is:

[0165] (1) 21 g of polyethersulfone, 1.2 g of polyvinylpyrrolidone, and 100 g of N,N-dimethylacetamide were mixed, and after stirring and dissolving completely, 3 g of the zirconium-based metal organic framework powder prepared in Example 3 was added, and the mixture was stirred and dispersed evenly at 30° C., and allowed to stand or vacuum degas to obtain a blended modified solution; wherein the mass ratio of the good solvent, the polysulfone material, the additive, and the metal organic framework material was 100:21:1.2:3;

[0166] (2) The blended modified solution obtained in step (1) is subjected to a non-solvent induced phase separation method, i.e., a metering pump is used to extrude the blended modified solution through the inner hole of a needle to form droplets in the air, and the droplets are dropped into water for phase conversion to form microspheres of uniform size. After washing and drying, a metal organic framework composite adsorbent is obtained.

[0167] The particle size of the metal organic framework composite adsorbent prepared in this example is about 1.1 mm.

[0168] Comparative Example 1

[0169] According to the method of Example 11, without adding metal organic framework material, polyethersulfone material microspheres are obtained.

[0170] The particle size of the polyethersulfone material microspheres prepared in this comparative example is about 1.1 mm.

[0171] Comparative Example 2

[0172] According to the method of Example 13, without adding metal organic framework material, polysulfone material microspheres are obtained.

[0173] The particle size of the polysulfone material microspheres prepared in this comparative example is about 1.0 mm.

[0174] Test Case

[0175] The material samples obtained in the above Examples 11 to 18 and Comparative Examples 1 to 2 were evaluated for their adsorption performance and safety using commercial perfusion resins HA130, BS330, and American cytosorb adsorbent as reference samples.

[0176] (1) Particle release detection

[0177] The microsphere materials prepared in Examples 11 to 18 of the present invention and Comparative Examples 1 to 2, reference samples and other materials were acid-washed, alkaline-washed and alcohol-rinsed; then, 100 ml of each sample was placed in a plastic container with a filter, and rinsed with water for injection until the particle detection value reached the requirement that the particle increment of 15 μm to 25 μm is ≤200 / 100 mL, and the particle increment of more than 25 μm is ≤100 / 100 mL. Afterwards, the plastic container containing the sample was sealed and placed on a simulated vehicle transport platform for vibration for 12 hours. Further, the liquid in the plastic container was taken and compared and calculated with the blank control sample. The results are shown in Table 1 below:

[0178] Table 1 Particle release test results of different samples

[0179]

[0180] From the results, it can be seen that the particle increment values ​​of the samples of Examples 11 to 18 of the present invention and Comparative Examples 1 to 2 are significantly smaller than those of the reference samples. This shows that the metal organic framework composite adsorbent prepared by the method of the present invention has the characteristic of less particle shedding.

[0181] (2) Evaluation of adsorption performance

[0182] The present invention evaluates the adsorption and removal performance of metal organic framework materials and metal organic framework composite adsorbents on target toxins in the field of blood perfusion, such as uremic protein-bound toxins, bilirubin, bile acid, endotoxin, etc.

[0183] For the adsorption performance test of the metal organic framework material powder prepared in Examples 1 to 10, the present invention uses PBS buffer solution to evaluate the adsorption performance of the metal organic framework material on uremic protein-bound toxins (p-cresol sulfate PCS, indoleacetic acid IAA) and bilirubin. That is: first, 250 mg of the metal organic framework material powder is dissolved in PBS buffer solution, centrifuged and washed several times, and drained; 10 mL of bovine serum albumin-PBS solution containing p-cresol sulfate PCS (25 mg / L), indole sulfate IS (25 mg / L), and bilirubin (300 μmol / L) are added respectively; after shaking at 37°C for 2 hours, the concentration changes of the adsorbed substances before and after are measured respectively, and the adsorption results are shown in Table 2 below:

[0184] Table 2 Toxin adsorption performance of different metal organic framework materials

[0185]

[0186] It can be seen from Table 2 that all metal organic framework material samples of Examples 1 to 10 of the present invention exhibit excellent adsorption performance of uremic protein-bound toxins (para-cresol sulfate PCS, indoleacetic acid IAA) and bilirubin.

[0187] With respect to the adsorption performance tests of the metal-organic framework composite adsorbents prepared in Examples 11 to 18 of the present invention, the microspheres prepared in Comparative Examples 1 to 2, and the reference samples, the present invention uses plasma solution to evaluate the adsorption performance of the metal-organic framework composite adsorbents and the adsorbents prepared in the comparative examples for uremic protein-bound toxins (p-cresol sulfate PCS, indoxyl sulfate IS, indoleacetic acid IAA), bilirubin, and bile acid. That is, first, the metal organic framework composite adsorbent, the adsorbent prepared in the comparative example and the reference sample to be tested were dissolved in PBS buffer solution, centrifuged and washed several times, and drained; 10 mL of plasma solution containing p-cresol sulfate PCS (25 mg / L), indoxyl sulfate IS (25 mg / L), indoleacetic acid IAA (10 mg / L), bilirubin (300 μmol / L), bile acid (150 μmol / L), and endotoxin (2EU / mL) were taken respectively, and 1 mL of the test material obtained in the above embodiment and comparative example was added, and after shaking at 37° C. for 2 hours, the concentration changes of the adsorbed substances before and after were respectively measured. The results are shown in Table 3 below:

[0188] Table 3 Toxin adsorption performance of different adsorbents

[0189]

[0190]

[0191] It can be seen from Table 3 that, in terms of uremic protein-bound toxins (para-cresol sulfate PCS, indoxyl sulfate IS, indoleacetic acid IAA, etc.), compared with HA130 hemoperfusion resin and control samples, the metal-organic framework composite adsorbent prepared in Examples 11 to 18 of the present invention has better adsorption performance; in terms of bilirubin, bile acid, and endotoxin adsorption, compared with BS330 hemoperfusion resin and control samples, the adsorption performance of the samples of the embodiments of the present invention is significantly better than that of the adsorbent prepared in Comparative Examples 1 to 2, and is basically close to that of BS330, or even better than BS330.

[0192] (3) Blood compatibility evaluation

[0193] The present invention evaluates the blood compatibility of the microspheres prepared in the comparative examples prepared in Examples 11 to 18 of the present invention, the adsorbents prepared in Comparative Examples 1 to 2, and the reference sample by the hemolysis rate performance index. The value of the hemolysis rate can directly reflect the blood compatibility of the material; a lower value reflects better blood compatibility.

[0194] Hemolysis rate test: The sample to be tested was washed with physiological saline for 5 times, and the washed sample was tested at a bath ratio of 5g / 10mL. The sample was incubated with diluted rabbit blood at 37°C, and the absorbance of hemoglobin released by red blood cell rupture was detected to calculate the hemolysis rate. The hemolysis rate index evaluation test results of different materials are shown in Table 4 below:

[0195] Table 4 Evaluation results of hemolysis rate index of different adsorbents

[0196] Hemolysis rate (%) Embodiment 11 0.3 Example 12 0.5 Embodiment 13 0.3 Embodiment 14 0.1 Embodiment 15 0.3 Example 16 0.4 Embodiment 17 0.2 Embodiment 18 0.4 Comparative Example 1 0.3 Comparative Example 2 0.5 HA130 resin 3.9 BS resin 8.6

[0197] From Table 4, it can be seen that the hemolysis rate of the metal organic framework composite adsorbent obtained by using Examples 11 to 18 of the present invention is less than 1%, which is similar to the hemolysis rate of the adsorbents of Comparative Examples 1 to 2 without metal organic framework materials, and is significantly lower than HA130 and BS330 resins. It can be seen that the metal organic framework composite adsorbent of the present invention has good blood compatibility. At the same time, the metal organic framework composite adsorbent prepared by Examples 11 to 18 of the present invention was tested for biocompatibility such as cytotoxicity, thrombosis, coagulation, complement activation, and immunity, and all showed good blood compatibility.

[0198] From the above results, it can be seen that the metal organic framework composite adsorbent provided by the present invention has excellent stability, blood compatibility and excellent adsorption of toxins, so the metal organic framework composite adsorbent prepared by the present invention is further prepared into a hemoperfusion device. The hemoperfusion device can be used for the clinical treatment of diseases and conditions such as renal failure, liver failure, acute poisoning, sepsis and septicemia, autoimmune diseases, inflammatory diseases, hyperlipidemia, etc.

[0199] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A metal organic framework composite adsorbent, wherein the metal organic framework composite adsorbent is a metal organic framework material-polysulfone material composite ball, and the mass ratio of the metal organic framework material to the polysulfone material in the metal organic framework material-polysulfone material composite ball is (1-10): (10-22).

2. The metal organic framework composite adsorbent according to claim 1, characterized in that: The metal organic framework material-polysulfone material composite ball is a spherical or quasi-spherical particle, and the particle size of the metal organic framework material-polysulfone material composite ball is 0.1-2.5 mm.

3. The metal organic framework composite adsorbent according to claim 1, characterized in that: The metal organic framework material includes one or more of a calcium-based metal organic framework, a calcium-based metal organic framework modified derivative, a zirconium-based metal organic framework and a zirconium-based metal organic framework modified derivative.

4. The metal organic framework composite adsorbent according to claim 3, characterized in that: The modifiers of the calcium-based metal-organic framework modified derivatives and the zirconium-based metal-organic framework modified derivatives independently include one or more of polyethyleneimine, diethylenetriamine, triethylenetetramine, tetraethylenepentamine, 1,3-propylenediamine, ethylenediamine, 3-dimethylaminopropylamine, tris(2-aminoethyl)amine, N,N'-di-n-propylethylenediamine, N,N-diethylethylenediamine, N,N-dibutylethylenediamine, N,N-dimethylethylenediamine, tris(3-aminopropyl)amine, 2,2'-diamino-N-methyldiethylamine, 3-diethylaminopropylamine, N'N-bis(3-aminopropyl)methylamine, 1,5-diaminopentane, N,N-diethyldiethylenetriamine, 1,6-hexanediamine and polyethylenepolyamine.

5. The metal organic framework composite adsorbent according to claim 1, characterized in that: The polysulfone material includes one or more of polysulfone, polyethersulfone, sulfonated polyethersulfone and polyarylsulfone.

6. The method for preparing the metal organic framework composite adsorbent according to any one of claims 1 to 5, comprising the following steps: (1) mixing a good solvent, a polysulfone material, an additive and a metal organic framework material to obtain a blended modified solution; (2) dropping the blended modified solution obtained in step (1) into a non-good solvent of the polysulfone material to perform phase separation to obtain a metal organic framework composite adsorbent.

7. The preparation method according to claim 6, characterized in that: The good solvent in step (1) includes one or more of N,N-dimethylformamide, N,N-dimethylacetamide and N-methylpyrrolidone.

8. The preparation method according to claim 6, characterized in that: The additive in step (1) includes one or more of polyethylene glycol, polyvinyl alcohol, polyvinyl pyrrolidone, water, ethylene glycol, n-propanol, isopropanol, glycerol, ethylene glycol methyl ether and lithium chloride.

9. The preparation method according to claim 6, characterized in that: The non-good solvent for the polysulfone material in step (2) includes a mixed solution of water and an organic solvent or water, and the organic solvent includes one or more of dimethyl sulfoxide, N,N-dimethylacetamide, N,N-dimethylformamide and N-methyl-2-pyrrolidone.

10. A hemoperfusion device, wherein the adsorbent of the hemoperfusion device is the metal-organic framework composite adsorbent according to any one of claims 1 to 5 or the metal-organic framework composite adsorbent prepared by the preparation method according to any one of claims 6 to 9.

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