Blood perfusion adsorbent with low protein adsorbability, preparation method of blood perfusion adsorbent and blood perfusion device

Abstract

The invention provides a blood perfusion adsorbent with low protein adsorbability, a preparation method of the blood perfusion adsorbent and a blood perfusion device, and belongs to the technical field of blood purification adsorbents. Vinyl silicone oil is introduced into the adsorbent, the adsorbent has low surface energy, excellent protein adsorption resistance and tissue and blood compatibility, and the surface of the cross-linked silicone oil modified adsorption resin prepared through suspension polymerization has a pore structure, so that the adsorption efficiency is improved. The adsorbent has relatively good blood compatibility, medium and macromolecular toxin adsorption performance and protein adsorption resistance; the cross-linked silicone oil modified adsorption resin is further subjected to a cross-linking reaction to obtain the hypercrosslinked silicone oil modified adsorption resin, and the hypercrosslinked silicone oil modified adsorption resin can still keep the protein adsorption resistance.

Description

Technical Field

[0001] The present invention relates to the technical field of blood purification adsorbents, and in particular to a blood perfusion adsorbent with low protein adsorption, 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 adsorbents 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 adsorbents generally have the problem of large protein adsorption. When the adsorbent has a large amount of protein adsorption, the following problems exist: first, the adsorbent material will be covered with a large amount of protein, reducing the adsorption efficiency of the target substance; second, the large amount of adsorbent protein adsorption will cause the adsorbent's blood compatibility to deteriorate; third, the loss of protein in the blood or plasma will have an adverse effect on the patient's body. At the same time, the above-mentioned materials generally have problems such as poor adsorption capacity for target toxins and poor blood compatibility.

[0004] Therefore, how to obtain an adsorbent with low protein adsorption, good blood compatibility and good adsorption performance for different toxins is a technical problem that needs to be solved urgently in the field of hemoperfusion adsorbent materials. Summary of the invention

[0005] The object of the present invention is to provide a blood perfusion adsorbent with low protein adsorption, a preparation method thereof and a blood perfusion device. The blood perfusion adsorbent with low protein adsorption provided by the present invention has low protein adsorption, 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 blood perfusion adsorbent with low protein adsorption, wherein the blood perfusion adsorbent with low protein adsorption comprises a cross-linked silicone oil modified adsorption resin or an ultra-high cross-linked silicone oil modified adsorption resin;

[0008] The cross-linked silicone oil modified adsorption resin is prepared by suspension polymerization of an oil phase and an aqueous phase; the oil phase comprises a styrene monomer, a vinyl silicone oil monomer, a porogen and an oily initiator; the aqueous phase comprises a dispersant and water;

[0009] The ultra-high cross-linked silicone oil modified adsorption resin is prepared by mixing the cross-linked silicone oil modified adsorption resin, an external cross-linking agent, a solvent and a catalyst through a cross-linking reaction.

[0010] Preferably, the viscosity of the vinyl silicone oil is 5 to 100 cs; the average molecular weight of the vinyl silicone oil is 400 to 5000.

[0011] Preferably, the vinyl silicone oil monomer includes at least one of single-end vinyl silicone oil, dual-end vinyl silicone oil, side-chain vinyl silicone oil and multifunctional vinyl silicone oil.

[0012] Preferably, the styrenic monomer comprises a polyvinyl aromatic monomer and / or a monovinyl aromatic monomer.

[0013] Preferably, the mass ratio of the styrene monomer, the vinyl silicone oil monomer, the porogen and the oily initiator is 1: (0.001-0.01): (0.3-3): (0.001-0.1);

[0014] The mass ratio of water to dispersant is 1:(0.0001-0.1);

[0015] The mass ratio of the oil phase to the water phase is 1:(1-5).

[0016] Preferably, the mass ratio of the cross-linked silicone oil modified adsorption resin, the external cross-linking agent, the solvent and the catalyst is 1:(0.01-3):(1-40):(0.01-3).

[0017] Preferably, the external crosslinking agent includes 4-aminobutyraldehyde dimethyl acetal, aminoacetaldehyde dimethyl acetal, aminoacetaldehyde diethyl acetal, methylaminoacetaldehyde dimethyl acetal, N,N-dimethylformamide dimethyl acetal, N,N-dimethylformamide diethyl acetal, N,N-dimethylformamide diisopropyl acetal, ethanolaldehyde diethyl acetal, 4,4-(dimethylamino)butyraldehyde diethyl acetal, (S)-2-hydroxypropionaldehyde dimethoxyacetal, succinaldehyde bis(dimethyl acetal), ethoxyacetaldehyde diethyl At least one of acetal, acetaldehyde diethyl acetal, butyraldehyde diethyl acetal, nonanal dimethyl acetal, citral dimethyl acetal, benzaldehyde diethyl acetal, isobutyraldehyde diethyl acetal, 2-chloroacetaldehyde dimethyl acetal, benzaldehyde dimethyl acetal, acrolein dimethyl acetal, propionaldehyde diethyl acetal, phenylacetaldehyde dimethyl acetal, 1,1,3,3-tetraethoxypropane, 1,1,3,3-tetramethoxypropane, triethyl orthoformate, trimethyl orthoformate, formaldehyde dimethyl acetal and acetaldehyde dimethyl acetal.

[0018] The present invention also provides a method for preparing the blood perfusion adsorbent with low protein adsorption as described in the above technical solution, comprising the following steps:

[0019] (1) mixing a styrene monomer, a vinyl silicone oil monomer, a porogen and an oily initiator to obtain an oil phase;

[0020] (2) dissolving the dispersant in water to obtain an aqueous phase;

[0021] (3) mixing the oil phase obtained in step (1) and the water phase obtained in step (2) to carry out a suspension polymerization reaction to obtain a cross-linked silicone oil-modified adsorption resin;

[0022] Alternatively, a cross-linked silicone oil modified adsorption resin, an external cross-linking agent, a solvent and a catalyst are mixed, and cross-linking reactions are performed in sequence to obtain an ultra-high cross-linked silicone oil modified adsorption resin;

[0023] The cross-linked silicone oil modified adsorption resin or the ultra-high cross-linked silicone oil modified adsorption resin is a blood perfusion adsorbent with low protein adsorption.

[0024] Preferably, the temperature of the suspension polymerization reaction in step (3) is 20 to 90° C., and the reaction time of the suspension polymerization reaction is 1 to 24 hours.

[0025] The present invention also provides a blood perfusion device, wherein the adsorbent of the blood perfusion device is the blood perfusion adsorbent with low protein adsorption described in the above technical solution or the blood perfusion adsorbent with low protein adsorption prepared by the preparation method described in the above technical solution.

[0026] The present invention provides a blood perfusion adsorbent with low protein adsorption, which includes a cross-linked silicone oil modified adsorption resin or an ultra-high cross-linked silicone oil modified adsorption resin; the cross-linked silicone oil modified adsorption resin is prepared by suspension polymerization of an oil phase and an aqueous phase; the oil phase includes a styrene monomer, a vinyl silicone oil monomer, a porogen and an oily initiator; the aqueous phase includes a dispersant and water; the ultra-high cross-linked silicone oil modified adsorption resin is prepared by mixing the cross-linked silicone oil modified adsorption resin, an external cross-linking agent, a solvent and a catalyst through a cross-linking reaction. The present invention introduces vinyl silicone oil into the adsorbent, which has low surface energy, excellent anti-protein adsorption performance and tissue and blood compatibility, and the cross-linked silicone oil modified adsorption resin prepared by suspension polymerization has a pore structure on its surface, which enables the adsorbent to have good blood compatibility, medium and macromolecular toxin adsorption performance and anti-protein adsorption performance; the present invention further cross-links the cross-linked silicone oil modified adsorption resin to obtain an ultra-high cross-linked silicone oil modified adsorption resin, which can still maintain anti-protein adsorption performance. The results of the embodiments show that the blood perfusion adsorbent with low protein adsorption provided by the present invention maintains a high adsorption rate for β2-microglobulin (β2-MG) and interleukin IL-6; has good adsorption performance for the protein-bound toxoid indoxyl sulfate IS; and the blood perfusion adsorbent with low protein adsorption provided by the present invention has a hemolysis rate of ≤0.1% and a platelet decrease rate of less than 6%, showing relatively good blood compatibility. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 This is a SEM image of the blood perfusion adsorbent with low protein adsorption prepared in Example 1 of the present invention with a scale of 1 μm;

[0028] Figure 2 This is a SEM image of the blood perfusion adsorbent with low protein adsorption prepared in Example 1 of the present invention with a scale of 500 nm;

[0029] Figure 3 This is an infrared spectrum of the blood perfusion adsorbent with low protein adsorption prepared in Example 1 of the present invention;

[0030] Figure 4 This is a SEM image of the blood perfusion adsorbent with low protein adsorption prepared in Example 4 of the present invention with a scale of 1 μm;

[0031] Figure 5 This is a SEM image of the blood perfusion adsorbent with low protein adsorption prepared in Example 4 of the present invention with a scale of 500 nm;

[0032] Figure 6 This is a SEM image of the blood perfusion adsorbent with low protein adsorption prepared in Example 9 of the present invention;

[0033] Figure 7 This is a SEM image of the blood perfusion adsorbent with low protein adsorption prepared in Example 10 of the present invention. DETAILED DESCRIPTION

[0034] The present invention provides a blood perfusion adsorbent with low protein adsorption, which comprises a cross-linked silicone oil modified adsorption resin or an ultra-high cross-linked silicone oil modified adsorption resin.

[0035] In the present invention, unless otherwise specified, the raw materials used in the present invention are all derived from commercially available products well known to those skilled in the art.

[0036] The blood perfusion adsorbent with low protein adsorption provided by the present invention comprises a cross-linked silicone oil modified adsorption resin.

[0037] In the present invention, the cross-linked silicone oil modified adsorption resin is prepared by suspension polymerization of an oil phase and an aqueous phase.

[0038] In the present invention, the oil phase comprises styrene monomers, vinyl silicone oil monomers, porogens and oily initiators; and the water phase comprises a dispersant and water.

[0039] In the present invention, the styrene monomer preferably includes a polyvinyl aromatic monomer and / or a monovinyl aromatic monomer. In the present invention, the polyvinyl aromatic monomer preferably includes one or more of divinylbenzene, a mixture of meta-divinylbenzene and para-divinylbenzene, trivinylbenzene, divinyltoluene, divinylxylene, divinylnaphthalene and derivatives thereof, more preferably meta-divinylbenzene and / or para-divinylbenzene. In the present invention, the derivative is preferably a halogenated compound, more preferably chlorodivinylbenzene. In an embodiment of the present invention, the styrene monomer may be divinylbenzene. The present invention does not specifically limit the source of the divinylbenzene, and conventional commercially available products may be used. In the present invention, commercially available divinylbenzene belongs to a polyvinyl aromatic monomer, and the usual purity is 55%, 63% or 80%. The purity of the divinylbenzene used in the embodiments of the present invention may be 55%, 63% or 80%.

[0040] In the present invention, the monovinyl aromatic monomer preferably includes styrene and C1-C4 alkyl-substituted styrene or C1-C4 alkyl-substituted styrene derivatives. In the present invention, the C1-C4 alkyl-substituted styrene preferably includes ethyl styrene, m-ethyl styrene and / or p-ethyl styrene; the C1-C4 alkyl-substituted styrene derivative preferably includes chlorostyrene or chloroethyl styrene. In an embodiment of the present invention, the monovinyl aromatic monomer may be at least one of styrene, m-ethyl styrene and p-ethyl styrene, more preferably a mixture of m-ethyl styrene and p-ethyl styrene or a mixture of styrene, m-ethyl styrene and p-ethyl styrene. The present invention does not specifically limit the proportion of each component in the mixture, and it can be adjusted as needed. The present invention uses the above-mentioned styrene monomer as one of the monomers of the adsorption resin, so that the blood perfusion adsorbent with low protein adsorption has good strength and toughness.

[0041] In the present invention, the viscosity of the vinyl silicone oil monomer is preferably 5 to 100 cs, more preferably 5 to 50 cs. In an embodiment of the present invention, the viscosity of the vinyl silicone oil monomer may be 5 cs, 10 cs, 20 cs or 50 cs. In the present invention, the average molecular weight of the vinyl silicone oil is preferably 400 to 5000, more preferably 800 to 4000. The present invention adopts the vinyl silicone oil monomer with the above parameters to prevent the viscosity of the vinyl silicone oil monomer from being too high. Although the obtained resin adsorbent can maintain good anti-protein adsorption performance, it will cause the pore structure on the surface of the adsorbent material to be unclear, thereby causing the adsorbent to significantly lose its adsorption performance for medium and macromolecular toxins. Therefore, the present invention controls the parameters of the vinyl silicone oil monomer within the above range, which is more conducive to forming a porous structure on the surface of the cross-linked silicone oil modified adsorption resin, and thus is more conducive to improving the adsorption performance and anti-protein adsorption performance of the cross-linked silicone oil modified adsorption resin.

[0042] In the present invention, the vinyl silicone oil monomer preferably includes at least one of single-end vinyl silicone oil, dual-end vinyl silicone oil, side-chain vinyl silicone oil and multifunctional vinyl silicone oil. In the present invention, the single-end vinyl silicone oil has only one vinyl functional group located at one end of the molecular chain; the chemical formula of the single-end vinyl silicone oil is preferably CH2=CH-Si(R)2-O-[Si(R)2-O] n-Si(R)3, wherein R is preferably a methyl group or a phenyl group. In the present invention, the dual-end vinyl silicone oil contains two vinyl functional groups, which are respectively located at the two ends of the molecular chain; the chemical formula of the dual-end vinyl silicone oil is preferably CH2=CH-Si(R)2-O-[Si(R)2-O]n-Si(R)2-CH=CH2, wherein R is preferably a methyl group or a phenyl group. In the present invention, the vinyl functional group of the side chain vinyl silicone oil is located on the side chain of the molecular chain; the chemical formula of the side chain vinyl silicone oil is preferably Si(R)2-O-[Si(R)(CH=CH2)-O] n -Si(R)3, wherein R is preferably a methyl group or a phenyl group. In the present invention, the molecular chain of the multifunctional vinyl silicone oil contains multiple (three or more) vinyl functional groups; the multifunctional vinyl silicone oil preferably includes methyl vinyl polysiloxane having vinyl groups at both ends and in the middle of the molecular chain. In an embodiment of the present invention, the model of the vinyl silicone oil monomer may be Jiangsu Keqi V-20 or Shanghai Yandi SHYH-VI401. The present invention adopts the above-mentioned vinyl silicone oil monomer, which has suitable viscosity, molecular weight and vinyl content, and is more conducive to improving the adsorption and anti-protein adsorption of the cross-linked silicone oil modified adsorption resin to toxins.

[0043] In the present invention, the porogen preferably includes at least one of benzene, toluene, xylene, ethylbenzene, methyl isobutyl carbinol, diisobutyl carbinol, isooctyl alcohol, cycloalkanes, paraffins, methyl silicone oil and industrial white oil, and more preferably one or more of benzene, toluene, xylene and isooctyl alcohol. The present invention can make the cross-linked silicone oil modified adsorption resin porous by using the porogen, increase the contact area between the resin and the substance to be adsorbed, and improve the adsorption capacity of macromolecular toxins. The present invention does not specifically limit the pore size on the cross-linked silicone oil modified adsorption resin, and can be adjusted according to the amount of porogen used.

[0044] In the present invention, the oily initiator preferably includes peroxide and / or azo compound; the peroxide is preferably dibenzoyl peroxide; the azo compound is preferably azobisisobutyronitrile. The present invention uses the above oily initiator to initiate the polymerization reaction of styrene monomers and vinyl silicone oil monomers.

[0045] In the present invention, the mass ratio of the styrene monomer, vinyl silicone monomer, porogen and oil initiator is preferably 1: (0.001-0.01): (0.3-3): (0.001-0.1), and more preferably 1: (0.005-0.01): (0.8-2): (0.015-0.1). The present invention controls the amount of each component within the above range to obtain an adsorbent material with better target toxin adsorption performance and low protein adsorption.

[0046] In the present invention, the aqueous phase includes a dispersant and water.

[0047] In the present invention, the dispersant preferably includes at least one of polyvinyl alcohol, gelatin and cellulose derivatives. In an embodiment of the present invention, the cellulose derivative can be polyvinyl alcohol (brand 1788), gelatin or hydroxypropyl methylcellulose. The present invention is more conducive to the full and uniform dispersion of each component and improves the uniformity of the resin by adding a dispersant.

[0048] In the present invention, the mass ratio of water to dispersant is preferably 1:(0.0001-0.1), more preferably 1:(0.001-0.1), and more preferably 1:(0.01-0.03). In an embodiment of the present invention, the mass ratio of water to dispersant may be 1:0.01875, 1:0.0167 or 1:0.03.

[0049] In the present invention, the mass ratio of the oil phase to the water phase is preferably 1: (1-5), more preferably 1: (3-5). In an embodiment of the present invention, the mass ratio of the oil phase to the water phase may be 1: 2, 1: 2.75, 1: 3.2 or 1: 4.48. The present invention can obtain a high-quality cross-linked silicone oil modified adsorption resin with uniform particle size distribution by controlling the mass ratio of the oil phase to the water phase within the above range.

[0050] The blood perfusion adsorbent with low protein adsorption provided by the present invention comprises an adsorption resin modified by ultra-high cross-linked silicone oil.

[0051] In the present invention, the ultra-high cross-linked silicone oil modified adsorption resin is prepared by mixing a cross-linked silicone oil modified adsorption resin, an external cross-linking agent, a solvent and a catalyst through a cross-linking reaction.

[0052] In the present invention, the cross-linked silicone oil modified adsorption resin is the same as the aforementioned cross-linked silicone oil modified adsorption resin.

[0053] In the present invention, the external crosslinking agent preferably includes 4-aminobutyraldehyde dimethyl acetal, aminoacetaldehyde dimethyl acetal, aminoacetaldehyde diethyl acetal, methylaminoacetaldehyde dimethyl acetal, N,N-dimethylformamide dimethyl acetal, N,N-dimethylformamide diethyl acetal, N,N-dimethylformamide diisopropyl acetal, ethanolaldehyde diethyl acetal, 4,4-(dimethylamino)butyraldehyde diethyl acetal, (S)-2-hydroxypropionaldehyde dimethoxyacetal, succinaldehyde bis(dimethyl acetal), ethoxyacetaldehyde diethyl acetal, acetaldehyde diethyl acetal, butyraldehyde diethyl acetal, nonyl At least one of acetaldehyde dimethyl acetal, citral dimethyl acetal, benzaldehyde diethyl acetal, isobutylaldehyde diethyl acetal, 2-chloroacetaldehyde dimethyl acetal, benzaldehyde dimethyl acetal, propionaldehyde dimethyl acetal, propionaldehyde diethyl acetal, phenylacetaldehyde dimethyl acetal, 1,1,3,3-tetraethoxypropane, 1,1,3,3-tetramethoxypropane, triethyl orthoformate, trimethyl orthoformate, formaldehyde dimethyl acetal and acetaldehyde dimethyl acetal, more preferably triethyl orthoformate, acetaldehyde dimethyl acetal, N,N-dimethylformamide diethyl acetal or aminoacetaldehyde dimethyl acetal. The present invention uses an external crosslinking agent to further crosslink the crosslinked silicone oil modified adsorption resin to form an ultra-high crosslinked silicone oil modified adsorption resin.

[0054] In the present invention, the solvent preferably includes at least one of dichloroethane, dichloromethane, nitrobenzene, toluene, xylene and benzene, and more preferably includes dichloroethane, nitrobenzene or toluene. The present invention adopts the above solvent, which is more conducive to fully swelling the cross-linked silicone oil modified adsorption resin, and then promotes the cross-linked silicone oil modified adsorption resin to further cross-link to form an ultra-high cross-linked silicone oil modified adsorption resin.

[0055] In the present invention, the catalyst preferably includes at least one of ferric chloride, aluminum chloride and zinc chloride, and more preferably ferric chloride or aluminum chloride. The catalyst added in the present invention can catalyze and promote the rapid cross-linking reaction.

[0056] In the present invention, the mass ratio of the cross-linked silicone oil modified adsorption resin, the external cross-linking agent, the solvent and the catalyst is preferably 1: (0.01-3): (1-40): (0.01-3), more preferably 1: (0.01-3): (1-40): (0.01-3)

[0057] The low protein adsorption blood perfusion adsorbent provided by the present invention has low surface energy, excellent anti-protein adsorption performance and tissue and blood compatibility by introducing vinyl silicone oil, and the surface of the cross-linked silicone oil modified adsorption resin prepared by suspension polymerization has a pore structure, which can enable the adsorbent to have good blood compatibility, medium and macromolecular toxin adsorption performance and anti-protein adsorption performance; the present invention further cross-links the cross-linked silicone oil modified adsorption resin to obtain an ultra-high cross-linked silicone oil modified adsorption resin, which can still maintain anti-protein adsorption performance.

[0058] The present invention also provides a method for preparing the blood perfusion adsorbent with low protein adsorption as described in the above technical solution, comprising the following steps:

[0059] (1) mixing a styrene monomer, a vinyl silicone oil monomer, a porogen and an oily initiator to obtain an oil phase;

[0060] (2) dissolving the dispersant in water to obtain an aqueous phase;

[0061] (3) The oil phase obtained in step (1) and the water phase obtained in step (2) are mixed to carry out a suspension polymerization reaction to obtain a cross-linked silicone oil modified adsorption resin.

[0062] The invention mixes styrene monomers, vinyl silicone oil monomers, porogens and oily initiators to obtain an oil phase.

[0063] In the present invention, the types and amounts of the styrene monomer, vinyl silicone oil monomer, porogen and oily initiator are the same as those in the above technical solution, and will not be described in detail herein.

[0064] The present invention has no particular limitation on the method for mixing the styrene monomer, vinyl silicone oil monomer, porogen and oily initiator, and a conventional mixing method can be used to dissolve the above components. In an embodiment of the present invention, the method for mixing the styrene monomer, vinyl silicone oil monomer, porogen and oily initiator can be stirring.

[0065] In the present invention, the dispersant is dissolved in water to obtain an aqueous phase.

[0066] In the present invention, the type of the dispersant is the same as the dispersant described in the above technical solution, and will not be described in detail here.

[0067] The present invention does not impose any particular limitation on the method for dissolving the dispersant in water, as long as the dispersant can be completely dissolved in water.

[0068] After obtaining the oil phase and the water phase, the present invention mixes the oil phase and the water phase to carry out suspension polymerization reaction to obtain a cross-linked silicone oil modified adsorption resin.

[0069] The present invention has no particular limitation on the method of mixing the oil phase and the water phase, as long as the two phases can be mixed evenly to form a uniformly dispersed emulsion.

[0070] In the present invention, the temperature of the suspension polymerization reaction is preferably 20 to 90° C., more preferably 75 to 80° C.; the reaction time of the suspension polymerization reaction is preferably 1 to 24 hours, more preferably 12 to 24 hours. The present invention controls the temperature and time within the above ranges, which is more conducive to promoting the full progress of the suspension polymerization reaction.

[0071] In the present invention, after the suspension polymerization reaction, the product obtained by the suspension polymerization reaction is preferably purified and dried to obtain a cross-linked silicone oil modified adsorption resin. The present invention has no special limitation on the operation method of the purification and drying, and conventional purification and drying methods can be used to fully remove impurities in the product obtained by the suspension polymerization reaction.

[0072] In another embodiment of the present invention, the method for preparing the blood perfusion adsorbent with low protein adsorption includes: mixing a cross-linked silicone oil modified adsorption resin, an external cross-linking agent, a solvent and a catalyst, and sequentially performing cross-linking reactions to obtain an ultra-high cross-linked silicone oil modified adsorption resin.

[0073] In the present invention, the types and amounts of the cross-linked silicone oil modified adsorption resin, external cross-linking agent, solvent and catalyst are the same as those in the above technical solution and will not be described in detail herein.

[0074] In the present invention, the method of mixing the cross-linked silicone oil modified adsorption resin, the external cross-linking agent and the solvent is preferably to stand at room temperature and then mix with the catalyst. The present invention can make the cross-linked silicone oil modified adsorption resin fully swell and be evenly mixed with other components by standing at room temperature. In an embodiment of the present invention, the standing time can be 12 hours.

[0075] In the present invention, the temperature of the cross-linking reaction is preferably 40 to 130°C, more preferably 60 to 80°C; the time of the cross-linking reaction is preferably 3 to 12 hours. In the present invention, the cross-linking reaction temperature method is preferably refluxed at the cross-linking reaction temperature. The present invention is more conducive to promoting further cross-linking of the cross-linked silicone oil modified adsorption resin by conducting the cross-linking reaction under the above conditions.

[0076] In the present invention, after the cross-linking reaction, the product obtained by the cross-linking reaction is preferably purified and dried to obtain an ultra-high cross-linked silicone oil modified adsorption resin. The present invention has no special restrictions on the operation method of the purification and drying, and conventional purification and drying methods are used to fully remove impurities in the product obtained by the cross-linking reaction.

[0077] The method provided by the present invention is simple and convenient, and its structure and performance are controllable, and an adsorbent with low protein adsorption, good blood compatibility and good adsorption performance for different toxins can be obtained.

[0078] The present invention also provides a blood perfusion device, wherein the adsorbent of the blood perfusion device is the blood perfusion adsorbent with low protein adsorption described in the above technical solution or the blood perfusion adsorbent with low protein adsorption prepared by the preparation method described in the above technical solution.

[0079] In the present invention, the hemoperfusion adsorbent can be used to remove endogenous or exogenous poisons or pathogenic substances in the blood. The hemoperfusion adsorbent of the present invention has low protein adsorption, good blood compatibility and good adsorption performance for different toxins, and can adsorb and remove uremic toxins (large molecular toxins in uremia, uremic protein-bound toxins, etc.), bilirubin and other toxins related to liver failure, bacterial toxins, inflammatory mediators, autoantibodies and immune complexes, high lipoproteins, etc.

[0080] 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.

[0081] Example 1

[0082] A blood perfusion adsorbent with low protein adsorption, wherein the blood perfusion adsorbent with low protein adsorption is a cross-linked silicone oil modified adsorption resin;

[0083] The cross-linked silicone oil modified adsorption resin is prepared by suspension polymerization of an oil phase and an aqueous phase; the oil phase is composed of a styrene monomer (divinylbenzene), a vinyl silicone oil monomer (vinyl-terminated polydimethylsiloxane, Jiangsu Keqi V-20, with a viscosity of about 5 cst and a molecular weight of about 800), a porogen (toluene and methyl isobutyl carbinol) and an oily initiator (benzoyl peroxide BPO); the aqueous phase is composed of a dispersant (gelatin) and water;

[0084] The mass ratio of the styrene monomer, vinyl silicone monomer, porogen and oily initiator is 1:0.01:1.005:0.015; the mass ratio of water and dispersant is 1:0.01875; the mass ratio of the oil phase and the water phase is 1:3.2;

[0085] The preparation method of the blood perfusion adsorbent with low protein adsorption is as follows:

[0086] (1) 100 g of divinylbenzene (63%), 1 g of vinyl silicone oil, 100 g of toluene, 50 g of methyl isobutyl carbinol, and 1.5 g of benzoyl peroxide BPO were mixed and dissolved uniformly to obtain an oil phase;

[0087] (2) 800 g of water and 15 g of gelatin were mixed and dissolved uniformly to obtain an aqueous phase;

[0088] (3) The oil phase is added to the water phase, and a suspension polymerization reaction is carried out at 79° C. for 12 hours. After the reaction is completed, a cross-linked silicone oil-modified adsorption resin is obtained through purification and post-treatment, which is a blood perfusion adsorbent with low protein adsorption.

[0089] The SEM images of the blood perfusion adsorbent with low protein adsorption prepared in this example at different scales are as follows: Figure 1 and 2 As shown. Figure 1 In the figure, the scale bar is 1 μm. Figure 2 In the figure, the scale bar is 500 nm. Figure 1 It can be seen that the blood perfusion adsorbent with low protein adsorption prepared in this example is a white regular sphere with a smooth surface. Figure 2 It can be seen that the microscopic surface of the blood perfusion adsorbent with low protein adsorption prepared by the present invention has an obvious pore structure.

[0090] The infrared spectrum of the blood perfusion adsorbent with low protein adsorption prepared in this example is as follows: Figure 3 As shown. Figure 3 It can be seen that at 1100cm -1 Si-O-Si asymmetric stretching vibration appears at 800-850cm -1 Symmetrical stretching vibrations of silicon-oxygen-silicon bonds occur, which indicates that vinyl silicone oil is successfully copolymerized into the molecular structure of the material.

[0091] Example 2

[0092] A blood perfusion adsorbent with low protein adsorption, wherein the blood perfusion adsorbent with low protein adsorption is a cross-linked silicone oil modified adsorption resin;

[0093] The cross-linked silicone oil modified adsorption resin is prepared by suspension polymerization of an oil phase and an aqueous phase; the oil phase is composed of a styrene monomer (divinylbenzene), a vinyl silicone oil monomer (vinyl-terminated polydimethylsiloxane, Jiangsu Keqi V-20, with a viscosity of about 5 cst and a molecular weight of about 800), a porogen (toluene, methyl isobutyl carbinol and methyl silicone oil) and an oily initiator (BPO); the aqueous phase is composed of a dispersant (gelatin) and water;

[0094] The mass ratio of the styrene monomer, vinyl silicone oil monomer, porogen and oily initiator is 1:0.005:1.2:0.02; the mass ratio of water and dispersant is 1:0.0167; the mass ratio of the oil phase and water phase is 1:2.75;

[0095] The preparation method of the blood perfusion adsorbent with low protein adsorption is as follows:

[0096] (1) 100 g of divinylbenzene (80%), 0.5 g of vinyl silicone oil, 80 g of toluene, 20 g of methyl isobutyl carbinol, 20 g of methyl silicone oil (10 cst), and 20 g of BPO were mixed and dissolved uniformly to obtain an oil phase;

[0097] (2) Mix and dissolve 600 g of water and 10 g of gelatin uniformly to obtain an aqueous phase;

[0098] (3) The oil phase is added to the water phase and a suspension polymerization reaction is carried out at 78° C. for 24 hours. After the reaction is completed, a cross-linked silicone oil-modified adsorption resin is obtained through purification and post-treatment, which is a blood perfusion adsorbent with low protein adsorption.

[0099] Example 3

[0100] A blood perfusion adsorbent with low protein adsorption, wherein the blood perfusion adsorbent with low protein adsorption is a cross-linked silicone oil modified adsorption resin;

[0101] The cross-linked silicone oil modified adsorption resin is prepared by suspension polymerization of an oil phase and an aqueous phase; the oil phase is composed of a styrene monomer (divinylbenzene), a vinyl silicone oil monomer (Shanghai Yandi SHYH-VI401, with a viscosity of about 20 cst and a molecular weight of about 2000, a porogen (toluene and methyl silicone oil) and an oily initiator (BPO); the aqueous phase is composed of a dispersant (gelatin) and water;

[0102] The mass ratio of the styrene monomer, vinyl silicone monomer, porogen and oily initiator is 1:0.001:1.5:0.02; the mass ratio of water and dispersant is 1:0.001; the mass ratio of the oil phase and the water phase is 1:2;

[0103] The preparation method of the blood perfusion adsorbent with low protein adsorption is as follows:

[0104] (1) 100 g of divinylbenzene (55%), 0.1 g of vinyl silicone oil, 100 g of toluene, 50 g of methyl silicone oil, and 2 g of BPO were mixed and dissolved uniformly to obtain an oil phase;

[0105] (2) 500 g of water and 0.5 g of hydroxypropyl methylcellulose were mixed and dissolved uniformly to obtain an aqueous phase;

[0106] (3) The oil phase is added to the water phase, and a suspension polymerization reaction is carried out at 80° C. for 12 hours. After the reaction is completed, a cross-linked silicone oil-modified adsorption resin is obtained through purification and post-treatment, which is a blood perfusion adsorbent with low protein adsorption.

[0107] Example 4

[0108] A blood perfusion adsorbent with low protein adsorption, wherein the blood perfusion adsorbent with low protein adsorption is a cross-linked silicone oil modified adsorption resin;

[0109] The cross-linked silicone oil modified adsorption resin is prepared by suspension polymerization of an oil phase and an aqueous phase; the oil phase is composed of styrene monomers (divinylbenzene and styrene), vinyl silicone oil monomers (Shanghai Yandi SHYH-VI401, with a viscosity of about 20 cst and a molecular weight of about 2000), a porogen (isopropanol) and an oily initiator (azobisisobutyronitrile AIBN); the aqueous phase is composed of a dispersant (polyvinyl alcohol 1788) and water;

[0110] The mass ratio of the styrene monomer, vinyl silicone monomer, porogen and oily initiator is 1:0.001:0.8:0.03; the mass ratio of water and dispersant is 1:0.03; the mass ratio of the oil phase and water phase is 1:4.48;

[0111] The preparation method of the blood perfusion adsorbent with low protein adsorption is as follows:

[0112] (1) 80 g of divinylbenzene (55%), 20 g of styrene, 1 g of vinyl silicone oil, 80 g of isopropanol, and 3 g of AIBN were mixed and dissolved uniformly to obtain an oil phase;

[0113] (2) 800 g of water and 24 g of polyvinyl alcohol 1788 were mixed and dissolved uniformly to obtain an aqueous phase;

[0114] (3) The oil phase is added to the water phase and a suspension polymerization reaction is carried out at 70° C. for 24 hours. After the reaction is completed, a cross-linked silicone oil-modified adsorption resin is obtained through purification and post-treatment, which is a blood perfusion adsorbent with low protein adsorption.

[0115] The SEM images of the blood perfusion adsorbent with low protein adsorption prepared in this example at different scales are as follows: Figure 4 and 5 As shown. Figure 4 In the figure, the scale bar is 1 μm. Figure 5 In the figure, the scale bar is 500 nm. Figure 4 It can be seen that the blood perfusion adsorbent with low protein adsorption prepared in this embodiment is a white regular sphere with a matte property. Figure 5 It can be seen that the microscopic surface of the blood perfusion adsorbent with low protein adsorption prepared by the present invention has an obvious pore structure.

[0116] Example 5

[0117] A blood perfusion adsorbent with low protein adsorption, wherein the blood perfusion adsorbent with low protein adsorption is an adsorption resin modified by ultra-high cross-linked silicone oil;

[0118] The ultra-high cross-linked silicone oil modified adsorption resin is prepared by mixing the cross-linked silicone oil modified adsorption resin prepared in Example 1, an external cross-linking agent (triethyl orthoformate), a solvent (ethylene dichloride) and a catalyst (ferric chloride) through a cross-linking reaction;

[0119] The preparation method of the blood perfusion adsorbent with low protein adsorption is as follows: 50g of the cross-linked silicone oil modified adsorption resin prepared in Example 1 is mixed with 1000g of ethylene dichloride and 40g of triethyl orthoformate, and 25g of ferric chloride is added after swelling at room temperature for 12h, and refluxed for 12h under a gradient temperature rising condition of 80°C, and purified to obtain an ultra-high cross-linked silicone oil modified adsorption resin, which is the low protein adsorption blood perfusion adsorbent.

[0120] Example 6

[0121] A blood perfusion adsorbent with low protein adsorption, wherein the blood perfusion adsorbent with low protein adsorption is an adsorption resin modified by ultra-high cross-linked silicone oil;

[0122] The ultra-high cross-linked silicone oil modified adsorption resin is prepared by mixing the cross-linked silicone oil modified adsorption resin prepared in Example 2, an external cross-linking agent (acetaldehyde dimethyl acetal), a solvent (ethylene dichloride) and a catalyst (ferric chloride) through a cross-linking reaction;

[0123] The preparation method of the blood perfusion adsorbent with low protein adsorption is as follows: 50g of the cross-linked silicone oil modified adsorption resin prepared in Example 2 is mixed with 1500g of dichloroethane and 50g of acetaldehyde dimethyl acetal, and after swelling at room temperature for 12h, 40g of ferric chloride is added and mixed, and refluxed for 48h under a gradient temperature rising condition of 78°C, and purified to obtain an ultra-high cross-linked silicone oil modified adsorption resin, which is the low protein adsorption blood perfusion adsorbent.

[0124] Example 7

[0125] A blood perfusion adsorbent with low protein adsorption, wherein the blood perfusion adsorbent with low protein adsorption is an adsorption resin modified by ultra-high cross-linked silicone oil;

[0126] The ultra-high cross-linked silicone oil modified adsorption resin is prepared by mixing the cross-linked silicone oil modified adsorption resin prepared in Example 3, an external cross-linking agent (N,N-dimethylformamide diethyl acetal), a solvent (nitrobenzene) and a catalyst (ferric chloride) through a cross-linking reaction;

[0127] The preparation method of the blood perfusion adsorbent with low protein adsorption is as follows: 50g of the cross-linked silicone oil modified adsorption resin prepared in Example 3 is mixed with 500g of nitrobenzene and 50g of N,N-dimethylformamide diethyl acetal, and 100g of ferric chloride is added after swelling at room temperature for 12h, and refluxed for 8h under a gradient temperature rising condition of 80°C, and purified to obtain an ultra-high cross-linked silicone oil modified adsorption resin, which is the low protein adsorption blood perfusion adsorbent.

[0128] Example 8

[0129] A blood perfusion adsorbent with low protein adsorption, wherein the blood perfusion adsorbent with low protein adsorption is an adsorption resin modified by ultra-high cross-linked silicone oil;

[0130] The ultra-high cross-linked silicone oil modified adsorption resin is prepared by mixing the cross-linked silicone oil modified adsorption resin prepared in Example 4, an external cross-linking agent (aminoacetaldehyde dimethyl acetal), a solvent (nitrobenzene) and a catalyst (aluminum trichloride) through a cross-linking reaction;

[0131] The preparation method of the blood perfusion adsorbent with low protein adsorption is as follows: 50g of the cross-linked silicone oil modified adsorption resin prepared in Example 4 is mixed with 750g of nitrobenzene and 25g of aminoacetaldehyde dimethyl acetal, and after swelling at room temperature for 12h, 2.5g of aluminum trichloride is added and mixed, and refluxed for 3h under a gradient temperature rising condition of 60°C, and purified to obtain an ultra-high cross-linked silicone oil modified adsorption resin, which is the low protein adsorption blood perfusion adsorbent.

[0132] Example 9

[0133] A blood perfusion adsorbent with low protein adsorption, wherein the blood perfusion adsorbent with low protein adsorption is a cross-linked silicone oil modified adsorption resin;

[0134] The cross-linked silicone oil modified adsorption resin is prepared by suspension polymerization of an oil phase and an aqueous phase; the oil phase is composed of a styrene monomer (divinylbenzene), a vinyl silicone oil monomer (vinyl-terminated polydimethylsiloxane, Jiangsu Keqi V-20, with a viscosity of about 5 cst and a molecular weight of about 800), a porogen (toluene and methyl isobutyl carbinol) and an oily initiator (benzoyl peroxide BPO); the aqueous phase is composed of a dispersant (gelatin) and water;

[0135] The mass ratio of the styrene monomer, vinyl silicone monomer, porogen and oily initiator is 1:0.05:1.005:0.015; the mass ratio of water and dispersant is 1:0.01875; the mass ratio of the oil phase and the water phase is 1:3.2;

[0136] The preparation method of the blood perfusion adsorbent with low protein adsorption is as follows:

[0137] (1) 100 g of divinylbenzene (63%), 5 g of vinyl silicone oil, 100 g of toluene, 50 g of methyl isobutyl carbinol, and 1.5 g of BPO were mixed and dissolved uniformly to obtain an oil phase;

[0138] (2) 800 g of water and 15 g of gelatin were mixed and dissolved uniformly to obtain an aqueous phase;

[0139] (3) The oil phase is added to the water phase, and a suspension polymerization reaction is carried out at 79° C. for 12 hours. After the reaction is completed, a cross-linked silicone oil-modified adsorption resin is obtained through purification and post-treatment, which is a blood perfusion adsorbent with low protein adsorption.

[0140] The SEM image of the blood perfusion adsorbent with low protein adsorption prepared in this example is as follows: Figure 6 As shown. Figure 6 It can be seen that this embodiment uses a relatively high content of vinyl silicone oil, and there is no obvious pore structure on the surface of the sample.

[0141] Example 10

[0142] A blood perfusion adsorbent with low protein adsorption, wherein the blood perfusion adsorbent with low protein adsorption is a cross-linked silicone oil modified adsorption resin;

[0143] The cross-linked silicone oil modified adsorption resin is prepared by suspension polymerization of an oil phase and an aqueous phase; the oil phase is composed of a styrene monomer (divinylbenzene), a vinyl silicone oil monomer (vinyl-terminated polydimethylsiloxane, Jiangsu Keqi V-500, with a viscosity of about 150 cst and a molecular weight of about 8000), a porogen (toluene and methyl isobutyl carbinol) and an oily initiator (benzoyl peroxide BPO); the aqueous phase is composed of a dispersant (gelatin) and water;

[0144] The mass ratio of the styrene monomer, vinyl silicone monomer, porogen and oily initiator is 1:0.05:1.005:0.015; the mass ratio of water and dispersant is 1:0.01875; the mass ratio of the oil phase and the water phase is 1:3.2;

[0145] The preparation method of the blood perfusion adsorbent with low protein adsorption is as follows:

[0146] (1) 100 g of divinylbenzene (63%), 5 g of vinyl silicone oil, 100 g of toluene, 50 g of methyl isobutyl carbinol, and 1.5 g of BPO were mixed and dissolved uniformly to obtain an oil phase;

[0147] (2) 800 g of water and 15 g of gelatin were mixed and dissolved uniformly to obtain an aqueous phase;

[0148] (3) The oil phase is added to the water phase, and a suspension polymerization reaction is carried out at 79° C. for 12 hours. After the reaction is completed, a cross-linked silicone oil-modified adsorption resin is obtained through purification and post-treatment, which is a blood perfusion adsorbent with low protein adsorption.

[0149] The SEM image of the blood perfusion adsorbent with low protein adsorption prepared in this example is as follows: Figure 7 As shown. Figure 7 It can be seen that this embodiment uses vinyl silicone oil with a relatively high viscosity, and there is no obvious pore structure on the surface of the sample.

[0150] Comparative Example 1

[0151] A method for preparing an adsorption composite material is as follows:

[0152] (1) 100 g of divinylbenzene (63%), 100 g of toluene, 50 g of methyl isobutyl carbinol, and 1.5 g of benzoyl peroxide (BPO) were mixed and dissolved uniformly to obtain an oil phase;

[0153] (2) 800 g of water and 15 g of gelatin were mixed and dissolved uniformly to obtain an aqueous phase;

[0154] (3) adding the oil phase to the water phase and carrying out suspension polymerization at 79° C. for 12 hours; after the reaction is completed, purification and post-treatment are performed to obtain a cross-linked adsorption resin.

[0155] Comparative Example 2

[0156] A method for preparing an adsorption composite material is as follows: 50 g of the cross-linked silicone oil modified adsorption resin prepared in comparative example 1 is mixed with 1000 g of ethylene dichloride and 40 g of triethyl orthoformate, and after swelling at room temperature for 12 hours, 25 g of ferric chloride is added and mixed, and refluxed for 12 hours under a gradient temperature rising condition of 80° C., and purified to obtain an ultra-high cross-linked adsorption resin.

[0157] Test Case

[0158] The adsorbents obtained in Examples 1 to 10, Comparative Examples 1 to 2 and the commercial cartridge resin CytoSorb TM The adsorbent and perfusion resin HA130 resin samples were used as adsorbent samples to be tested, and the protein adsorption performance, target toxin adsorption performance and related safety evaluation were carried out in turn.

[0159] (1) Evaluation of protein adsorption performance

[0160] The protein adsorption rate test method is as follows: the adsorbent sample to be tested is washed with physiological saline for 5 times, and the washed sample is tested at a bath ratio of 1mL / 10mL. The sample is in dynamic contact with plasma at 170r / min at 37°C for 120min, and the content of albumin and total protein before and after adsorption is detected, and the adsorption rate is calculated. The structure is shown in Table 1.

[0161] Table 1 Evaluation results of protein adsorption performance of different adsorbent samples

[0162]

[0163]

[0164] As can be seen from Table 1, the adsorption rates of albumin and total protein of the blood perfusion adsorbents with low protein adsorption prepared in Examples 1 to 10 of the present invention are all lower than 1%. Compared with Comparative Examples 1 to 2 and commercial resins, the protein adsorption rates of the embodiments of the present invention are significantly reduced. It can be seen that the introduction of organosilicon components into the blood perfusion adsorbents with low protein adsorption can effectively improve the anti-protein adsorption performance of the resin.

[0165] (2) Evaluation of adsorption performance

[0166] 10 mL of plasma solution containing β2-microglobulin (β2-MG), interleukin-6 (IL-6), and indoxyl sulfate IS were taken respectively, and 1 mL of the adsorption resin obtained from the above-mentioned adsorbent sample was added respectively. After shaking at 37°C for 2 h, the changes of the adsorbed substances were measured respectively. The results are shown in Table 2.

[0167] Table 2 Toxin adsorption performance of different adsorbent samples

[0168]

[0169]

[0170] As can be seen from Table 2, the low protein adsorption blood perfusion adsorbents prepared in Examples 1 to 8 of the present invention all maintain high adsorption rates for β2-microglobulin (β2-MG) and interleukin IL-6, and are even better than HA130 resin; in addition, the low protein adsorption blood perfusion adsorbents prepared in Examples 7 and 8 have good adsorption performance for protein-bound toxin indoxyl sulfate IS, which is significantly better than other HA130 resins, which should be attributed to the amine groups introduced during the post-crosslinking process of the resin. The low protein adsorption blood perfusion adsorbents prepared in Examples 9 to 10 have significantly reduced adsorption performance for macromolecular toxins, which is related to the fact that Examples 9 and 10 use high-content and high-viscosity vinyl silicone oils, respectively, resulting in unclear pore structures on the surface of the adsorbent resin. It can be seen that the properties and dosage of the vinyl silicone oil of the present invention have a direct impact on the surface pore structure and adsorption performance of the resin adsorbent. And using vinyl silicone oil with a viscosity of 5-100cs and an average molecular weight of 400-5000, and controlling the mass ratio of vinyl silicone oil monomer to styrene monomer to be (0.001-0.01):1, it is more conducive to obtaining both good medium and large molecular toxin performance and anti-protein adsorption performance.

[0171] (3) Blood compatibility evaluation

[0172] The present invention evaluates the blood compatibility of the adsorbent sample to be tested by performance indicators such as hemolysis rate and platelet count test. The values ​​of hemolysis rate and platelet reduction rate can directly reflect the blood compatibility of the material; lower values ​​reflect better blood compatibility.

[0173] The hemolysis rate test method is as follows: the adsorbent sample to be tested is washed 5 times with normal saline, and the washed sample is tested at a bath ratio of 5g / 10mL. The sample is incubated with diluted rabbit blood at 37°C, the absorbance of hemoglobin released by red blood cell fragmentation is detected, and the hemolysis rate is calculated. Platelet count test: The resin sample is washed 5 times with normal saline, and the washed sample is tested at a bath ratio of 0.2g / ml. The sample is in dynamic contact with whole blood at 37°C at 30r / min for 60min, and the number of platelets in the whole blood is detected using a blood cell analyzer, and the platelet decrease rate is calculated. The blood compatibility index evaluation test results of different adsorbent samples to be tested are shown in Table 3 below.

[0174] Table 3 Blood compatibility index evaluation test results of different adsorbent samples

[0175] Hemolysis rate (%) Platelet decrease rate (%) Example 1 0.4 4.5 Example 2 0.2 3.8 Example 3 0.2 4.2 Example 4 0.6 5.5 Example 5 0.5 3.6 Example 6 0.4 3.5 Example 7 0.9 4.9 Example 8 0.8 5.2 Example 9 0.1 2.8 Example 10 0.3 3.1 Comparative Example 1 1.8 18.4 Comparative Example 2 1.2 16.9 HA130 resin 3.2 19.6

[0176] As can be seen from Table 3, the hemolysis rate of the low protein adsorption blood perfusion adsorbent obtained by Examples 1 to 10 of the present invention is ≤0.1%, and the platelet reduction rate is less than 6%. Compared with Control Examples 1 to 2 and HA130 resin, the low protein adsorption blood perfusion adsorbent provided by the embodiments of the present invention exhibits good blood compatibility. At the same time, the low protein adsorption blood perfusion adsorbent of Examples 1 to 10 of the present invention was tested for biocompatibility such as cytotoxicity, thrombosis, coagulation, complement activation, and immunity, and all showed excellent blood compatibility results.

[0177] It can be seen from the above results that the low protein adsorption blood perfusion adsorbent provided by the present invention maintains a high adsorption rate for β2-microglobulin (β2-MG) and interleukin IL-6; has good adsorption performance for protein-bound toxin indoxyl sulfate IS; and the low protein adsorption blood perfusion adsorbent provided by the present invention has a hemolysis rate of ≤0.1% and a platelet decrease rate of less than 6%, showing good blood compatibility. Therefore, it can be used as an adsorbent for blood perfusion devices.

[0178] 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 blood perfusion adsorbent with low protein adsorption, comprising a cross-linked silicone oil modified adsorption resin or an ultra-high cross-linked silicone oil modified adsorption resin; The cross-linked silicone oil modified adsorption resin is prepared by suspension polymerization of an oil phase and an aqueous phase; the oil phase comprises a styrene monomer, a vinyl silicone oil monomer, a porogen and an oily initiator; the aqueous phase comprises a dispersant and water; The ultra-high cross-linked silicone oil modified adsorption resin is prepared by mixing the cross-linked silicone oil modified adsorption resin, an external cross-linking agent, a solvent and a catalyst through a cross-linking reaction.

2. The blood perfusion adsorbent with low protein adsorption according to claim 1, It is characterized in that The viscosity of the vinyl silicone oil is 5 to 100 cs; the average molecular weight of the vinyl silicone oil is 400 to 5000.

3. The blood perfusion adsorbent with low protein adsorption according to claim 1 or 2, It is characterized in that The vinyl silicone oil monomer includes at least one of single-end vinyl silicone oil, dual-end vinyl silicone oil, side-chain vinyl silicone oil and multifunctional vinyl silicone oil.

4. The blood perfusion adsorbent with low protein adsorption according to claim 1, It is characterized in that The styrenic monomers include polyvinyl aromatic monomers and / or monovinyl aromatic monomers.

5. The blood perfusion adsorbent with low protein adsorption according to claim 1, It is characterized in that The mass ratio of the styrene monomer, the vinyl silicone oil monomer, the porogen and the oily initiator is 1: (0.001-0.01): (0.3-3): (0.001-0.1); The mass ratio of water to dispersant is 1:(0.0001-0.1); The mass ratio of the oil phase to the water phase is 1:(1-5).

6. The blood perfusion adsorbent with low protein adsorption according to claim 1 or 5, It is characterized in that The mass ratio of the cross-linked silicone oil modified adsorption resin, the external cross-linking agent, the solvent and the catalyst is 1:(0.01-3):(1-40):(0.01-3).

7. The blood perfusion adsorbent with low protein adsorption according to claim 1, It is characterized in that The external crosslinking agent includes 4-aminobutyraldehyde dimethyl acetal, aminoacetaldehyde dimethyl acetal, aminoacetaldehyde diethyl acetal, methylaminoacetaldehyde dimethyl acetal, N,N-dimethylformamide dimethyl acetal, N,N-dimethylformamide diethyl acetal, N,N-dimethylformamide diisopropyl acetal, ethanolaldehyde diethyl acetal, 4,4-(dimethylamino)butyraldehyde diethyl acetal, (S)-2-hydroxypropionaldehyde dimethoxyacetal, succinaldehyde bis(dimethyl acetal), ethoxyacetaldehyde diethyl acetal At least one of aldehyde, acetaldehyde diethyl acetal, butyraldehyde diethyl acetal, nonanal dimethyl acetal, citral dimethyl acetal, benzaldehyde diethyl acetal, isobutyraldehyde diethyl acetal, 2-chloroacetaldehyde dimethyl acetal, benzaldehyde dimethyl acetal, acrolein dimethyl acetal, propionaldehyde diethyl acetal, phenylacetaldehyde dimethyl acetal, 1,1,3,3-tetraethoxypropane, 1,1,3,3-tetramethoxypropane, triethyl orthoformate, trimethyl orthoformate, formaldehyde dimethyl acetal and acetaldehyde dimethyl acetal.

8. A method for preparing the blood perfusion adsorbent with low protein adsorption according to any one of claims 1 to 7, The following steps are involved: (1) mixing a styrene monomer, a vinyl silicone oil monomer, a porogen and an oily initiator to obtain an oil phase; (2) dissolving the dispersant in water to obtain an aqueous phase; (3) mixing the oil phase obtained in step (1) and the water phase obtained in step (2) to carry out a suspension polymerization reaction to obtain a cross-linked silicone oil-modified adsorption resin; Alternatively, a cross-linked silicone oil modified adsorption resin, an external cross-linking agent, a solvent and a catalyst are mixed, and cross-linking reactions are performed in sequence to obtain an ultra-high cross-linked silicone oil modified adsorption resin; The cross-linked silicone oil modified adsorption resin or the ultra-high cross-linked silicone oil modified adsorption resin is a blood perfusion adsorbent with low protein adsorption.

9. The preparation method according to claim 8, It is characterized in that The temperature of the suspension polymerization reaction in step (3) is 20 to 90° C., and the reaction time of the suspension polymerization reaction is 1 to 24 hours.

10. A blood perfusion device, wherein the blood perfusion device adsorbent is the blood perfusion adsorbent with low protein adsorption according to any one of claims 1 to 7 or the blood perfusion adsorbent with low protein adsorption prepared by the preparation method according to any one of claims 8 to 9.

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