A low-protein adsorptive hemoperfusion adsorbent, a preparation method thereof, and a hemoperfusion device

Abstract

The application provides a blood perfusion adsorbent with low protein adsorption, a preparation method thereof and a blood perfusion device, and belongs to the technical field of blood purification adsorbents. The application introduces vinyl silicone oil into the adsorbent, the vinyl silicone oil has low surface energy, excellent anti-protein adsorption performance 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 adsorbent has good blood compatibility, medium and large molecule toxin adsorption performance and anti-protein adsorption performance. The cross-linked silicone oil modified adsorption resin is further subjected to cross-linking reaction to obtain an ultra-high cross-linked silicone oil modified adsorption resin, and the ultra-high cross-linked silicone oil modified adsorption resin still has anti-protein adsorption performance.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of blood purification adsorbent, in particular to a low-protein adsorption blood perfusion adsorbent, a preparation method thereof and a blood perfusion device. BACKGROUND

[0002] Blood perfusion adsorbents can remove pollutants by non-specific or specific adsorption of toxins, drugs and metabolites, thereby achieving the purpose of purifying blood. At present, common adsorbents for blood perfusion adsorbents include activated carbon and resin, etc. These materials can effectively adsorb and remove harmful substances such as toxins, metabolites and immune complexes in blood, and have wide application in the fields of kidney disease, liver disease, immune disease, drug overdose, critical illness, etc.

[0003] However, it is found in clinical treatment and scientific research experiments that the above-mentioned adsorbents generally have the problem of large protein adsorption amount. When the adsorbent has a large protein adsorption amount, the following problems exist: first, the adsorbent material will be covered by a large amount of protein, reducing the adsorption efficiency of the target substance; second, a large protein adsorption amount of the adsorbent will cause poor blood compatibility of the adsorbent; third, the loss of protein in blood or plasma will have an adverse effect on the patient's body. At the same time, the above-mentioned materials generally have the problems of poor adsorption capacity for target toxins and poor blood compatibility.

[0004] Therefore, how to obtain an adsorbent with low protein adsorption amount, good blood compatibility and good adsorption performance for different toxins is a technical problem to be solved in the field of blood perfusion adsorbent materials at present. SUMMARY

[0005] The present application aims to provide a low-protein adsorption blood perfusion adsorbent, a preparation method thereof and a blood perfusion device. The low-protein adsorption blood perfusion adsorbent provided by the present application has low protein adsorption amount, good blood compatibility and excellent adsorption performance for different toxins.

[0006] In order to achieve the above-mentioned application purposes, the present application provides the following technical solutions:

[0007] The present application provides a low-protein adsorption blood perfusion adsorbent, which comprises a cross-linked silicone oil modified adsorption resin or an ultrahigh 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 styrene monomers, vinyl silicone oil monomers, a pore-forming agent and an oily initiator; and the aqueous phase comprises a dispersing agent and water.

[0009] The super-high crosslinking silicone oil modified adsorption resin is prepared by mixing the crosslinking type silicone oil modified adsorption resin, an external crosslinking agent, a solvent and a catalyst, and through a crosslinking reaction.

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

[0011] Preferably, the vinyl silicone oil monomer comprises at least one of a single-terminal vinyl silicone oil, a double-terminal vinyl silicone oil, a side-chain vinyl silicone oil and a multi-function vinyl silicone oil.

[0012] Preferably, the styrene monomer comprises a multi-vinyl aromatic monomer and / or a mono-vinyl 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 the water and the dispersant is 1:(0.0001-0.1).

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

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

[0017] Preferably, the external crosslinking agent comprises at least one of 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, ethanol aldehyde diethyl acetal, 4,4-(dimethylamino)butyraldehyde diethyl acetal, (S)-2-hydroxypropanal dimethoxy acetal, succinic aldehyde bis(dimethyl acetal), ethoxyacetaldehyde diethyl 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, 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.

[0018] The application further provides a preparation method of the blood perfusion adsorbent with low protein adsorption property.

[0019] (1) mixing styrene monomer, vinyl silicone oil monomer, pore-forming agent and oily initiator to obtain an oil phase;

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

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

[0022] or, mixing the cross-linked silicone oil modified adsorption resin, external cross-linking agent, solvent and catalyst to sequentially perform a cross-linking reaction to obtain a super-high cross-linked silicone oil modified adsorption resin;

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

[0024] Preferably, the temperature of the suspension polymerization reaction in step (3) is 20-90℃, and the reaction time of the suspension polymerization reaction is 1-24h.

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

[0026] This invention provides a hemoperfusion adsorbent with low protein adsorption, comprising a cross-linked silicone oil-modified adsorbent resin or a highly cross-linked silicone oil-modified adsorbent resin. The cross-linked silicone oil-modified adsorbent resin is prepared by suspension polymerization of an oil phase and an aqueous phase. The oil phase comprises styrene monomers, vinyl silicone oil monomers, a porogen, and an oily initiator. The aqueous phase comprises a dispersant and water. The highly cross-linked silicone oil-modified adsorbent resin is prepared by mixing the cross-linked silicone oil-modified adsorbent resin, an external cross-linking agent, a solvent, and a catalyst, and then reacting them via a cross-linking reaction. This invention introduces vinyl silicone oil into the adsorbent, which possesses low surface energy, excellent anti-protein adsorption properties, and tissue and blood compatibility. Furthermore, the cross-linked silicone oil-modified adsorbent resin prepared by suspension polymerization has a porous surface structure, enabling the adsorbent to possess good blood compatibility, adsorption performance for medium and large molecular weight toxins, and anti-protein adsorption properties. This invention further cross-links the cross-linked silicone oil-modified adsorbent resin to obtain a highly cross-linked silicone oil-modified adsorbent resin, which still maintains its anti-protein adsorption properties. The results of the examples show that the low protein adsorption hemoperfusion adsorbent provided by the present invention maintains a high adsorption rate for β2-microglobulin (β2-MG) and interleukin IL-6; it has good adsorption performance for the protein-bound toxin indophenol sulfate (IS); and the low protein adsorption hemoperfusion adsorbent provided by the present invention has a hemolysis rate of ≤0.1% and a platelet decrease rate of less than 6%, exhibiting good blood compatibility. Attached Figure Description

[0027] Figure 1 This is a SEM image of the low protein adsorption hemoperfusion adsorbent prepared in Example 1 of the present invention, with a scale bar of 1 μm.

[0028] Figure 2 SEM image of the low protein adsorption hemoperfusion adsorbent prepared in Example 1 of the present invention, with a scale bar of 500 nm.

[0029] Figure 3 The infrared spectrum of the low protein adsorption hemoperfusion adsorbent prepared in Example 1 of this invention;

[0030] Figure 4 This is a SEM image of the low protein adsorption hemoperfusion adsorbent prepared in Example 4 of the present invention, with a scale bar of 1 μm.

[0031] Figure 5 This is a SEM image of the low protein adsorption hemoperfusion adsorbent prepared in Example 4 of the present invention, with a scale bar of 500 nm.

[0032] Figure 6 SEM image of the low protein adsorption hemoperfusion adsorbent prepared in Example 9 of this invention;

[0033] Figure 7 SEM image of the low protein adsorbing blood perfusion adsorbent prepared for Example 10 of the present application. DETAILED DESCRIPTION

[0034] The present application provides a low protein adsorbing blood perfusion adsorbent, which comprises a cross-linked silicone oil modified adsorption resin or a super-high cross-linked silicone oil modified adsorption resin.

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

[0036] The present application provides a low protein adsorbing blood perfusion adsorbent, which comprises a cross-linked silicone oil modified adsorption resin.

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

[0038] In the present application, the oil phase comprises a styrene monomer, a vinyl silicone oil monomer, a pore-forming agent and an oily initiator; and the water phase comprises a dispersant and water.

[0039] In the present application, the styrene monomer preferably comprises a polyvinyl aromatic monomer and / or a monovinyl aromatic monomer. In the present application, the polyvinyl aromatic monomer preferably comprises one or more of a mixture of divinylbenzene, m-divinylbenzene and p-divinylbenzene, trivinylbenzene, divinyltoluene, divinylxylene, divinylnaphthalene and derivatives thereof, and more preferably m-divinylbenzene and / or p-divinylbenzene. In the present application, the derivative is preferably a halide, and more preferably chlorinated divinylbenzene. In the embodiments of the present application, the styrene monomer can be divinylbenzene. The present application does not have a special limitation on the source of the divinylbenzene, and a conventional commercially available product can be used. In the present application, the commercially available divinylbenzene belongs to the polyvinyl aromatic monomer, and the purity is usually 55%, 63% or 80%. The purity of the divinylbenzene used in the embodiments of the present application can be 55%, 63% or 80%.

[0040] In the present application, the monovinyl aromatic monomer preferably includes styrene and C1-C4 alkyl substituted styrene or C1-C4 alkyl substituted styrene derivatives. In the present application, the C1-C4 alkyl substituted styrene preferably includes ethyl styrene, m-ethyl styrene and / or p-ethyl styrene; the C1-C4 alkyl substituted styrene derivatives preferably include chlorostyrene or chloroethyl styrene. In the embodiments of the present application, the monovinyl aromatic monomer can 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 consisting of styrene, m-ethyl styrene and p-ethyl styrene. The present application does not make special limitation to the proportion of each component in the mixture, which can be adjusted as required. The present application uses the above-mentioned styrene monomer as one of the monomers of the adsorption resin, so that the hemoperfusion adsorbent with low protein adsorption has good strength and toughness.

[0041] In the present application, the viscosity of the vinyl silicone oil monomer is preferably 5-100 cs, more preferably 5-50 cs. In the embodiments of the present application, the viscosity of the vinyl silicone oil monomer can be 5 cs, 10 cs, 20 cs or 50 cs. In the present application, the average molecular weight of the vinyl silicone oil is preferably 400-5000, more preferably 800-4000. The present application uses the vinyl silicone oil monomer with the above-mentioned parameters, which can prevent the viscosity of the vinyl silicone oil monomer from being too high, although the obtained resin adsorbent can maintain good protein adsorption resistance, but will cause the pore structure on the surface of the adsorbent material to be not obvious, thereby causing the adsorbent to obviously lose the adsorption performance for medium and large molecular toxins. Therefore, the present application controls the parameters of the vinyl silicone oil monomer in the above-mentioned range, which is more beneficial to form a porous structure on the surface of the cross-linked silicone oil modified adsorption resin, and further more beneficial to improve the adsorption performance and protein adsorption resistance of the cross-linked silicone oil modified adsorption resin.

[0042] In the present application, the vinyl silicone oil monomer preferably includes at least one of single-terminal vinyl silicone oil, double-terminal vinyl silicone oil, side-chain vinyl silicone oil and multi-functional vinyl silicone oil. In the present application, the single-terminal vinyl silicone oil has only one vinyl functional group at one end of the molecular chain; the chemical formula of the single-terminal vinyl silicone oil is preferably CH2=CH-Si(R)2-O-[Si(R)2-O] n-Si(R)3, R is preferably methyl or phenyl. In the present application, the double-end vinyl silicone oil contains two vinyl functional groups at both ends of the molecular chain; the chemical formula of the double-end vinyl silicone oil is preferably CH2=CH-Si(R)2-O-[Si(R)2-O]n-Si(R)2-CH=CH2, R is preferably methyl or phenyl. In the present application, the side-chain vinyl silicone oil has vinyl functional groups 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, R is preferably methyl or phenyl. In the present application, the multi-functional vinyl silicone oil contains multiple (three or more) vinyl functional groups on the molecular chain; the multi-functional vinyl silicone oil preferably includes methyl vinyl polysiloxane with vinyl groups at both ends and in the middle of the molecular chain. In the embodiments of the present application, the type of the vinyl silicone oil monomer can be Jiangsu Keqi V-20 or Shanghai Yandy SHYH-VI401. The use of the above-mentioned vinyl silicone oil monomer in the present application has appropriate viscosity, molecular weight and vinyl content, which is more conducive to improving the adsorption of cross-linked silicone oil modified adsorption resin to toxins and the resistance to protein adsorption.

[0043] In the present application, the pore-forming agent preferably includes at least one of benzene, toluene, xylene, ethylbenzene, methyl isobutyl carbinol, diisobutyl carbinol, isooctanol, cycloalkane, alkane, methyl silicone oil and industrial white oil, and more preferably one or more of benzene, toluene, xylene and isooctanol. The use of the pore-forming agent in the present application can make the cross-linked silicone oil modified adsorption resin have porosity, increase the contact area of the resin with the adsorbed substance, and improve the adsorption capacity of macromolecular toxins. The present application does not specially limit the pore size of the cross-linked silicone oil modified adsorption resin, which can be adjusted according to the amount of the pore-forming agent used.

[0044] In the present application, the oil initiator preferably includes peroxide and / or azo compound; the peroxide is preferably dibenzoyl peroxide; and the azo compound is preferably azobisisobutyronitrile. The use of the above-mentioned oil initiator in the present application can initiate the polymerization reaction of the styrene monomer and the vinyl silicone oil monomer.

[0045] In the present application, the mass ratio of the styrene monomer, the vinyl silicone oil monomer, the pore-forming agent and the 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 control of the amount of each component in the above-mentioned range in the present application can obtain an adsorbent material with good target toxin adsorption performance and low protein adsorption capacity.

[0046] In the present application, the water phase comprises a dispersant and water.

[0047] In the present application, the dispersant preferably comprises at least one of polyvinyl alcohol, gelatin and cellulose derivatives. In the embodiments of the present application, the cellulose derivative can be polyvinyl alcohol (grade 1788), gelatin or hydroxypropyl methyl cellulose. The present application is more conducive to the uniform dispersion of the components and the improvement of the uniformity of the resin by adding the dispersant.

[0048] In the present application, the mass ratio of the water and the dispersant is preferably 1:(0.0001-0.1), more preferably 1:(0.001-0.1), and more preferably 1:(0.01-0.03). In the embodiments of the present application, the mass ratio of the water and the dispersant can be 1:0.01875, 1:0.0167 or 1:0.03.

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

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

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

[0052] In the present application, 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 application, the external cross-linking agent preferably comprises at least one of 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, ethanol aldehyde diethyl acetal, 4,4-(dimethylamino)butyraldehyde diethyl acetal, (S)-2-hydroxypropanal dimethoxyethyl acetal, succinaldehyde bis(dimethyl acetal), ethoxyacetaldehyde diethyl 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, 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 application uses the external cross-linking agent to further cross-link the cross-linked silicone oil modified adsorption resin to form the ultra-high cross-linked silicone oil modified adsorption resin.

[0054] In the present application, the solvent preferably comprises at least one of dichloroethane, dichloromethane, nitrobenzene, toluene, xylene and benzene, more preferably dichloroethane, nitrobenzene or toluene. The present application uses the above solvent, which is more conducive to fully swelling the cross-linked silicone oil modified adsorption resin, thereby promoting the further cross-linking of the cross-linked silicone oil modified adsorption resin to form the ultra-high cross-linked silicone oil modified adsorption resin.

[0055] In the present application, the catalyst preferably comprises at least one of ferric chloride, aluminum chloride and zinc chloride, more preferably ferric chloride or aluminum chloride. The present application adds the catalyst, which can catalyze and promote the cross-linking reaction to proceed rapidly.

[0056] In the present application, 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 application has low surface energy, excellent anti-protein adsorption performance and tissue and blood compatibility by introducing vinyl silicone oil. The cross-linked silicone oil modified adsorption resin prepared by suspension polymerization has a pore structure on the surface, which can make the adsorbent have better blood compatibility, medium and large molecule toxin adsorption performance and anti-protein adsorption performance. The cross-linked silicone oil modified adsorption resin is further cross-linked in the present application to obtain the ultra-high cross-linked silicone oil modified adsorption resin, which still has anti-protein adsorption performance.

[0058] The application further provides a preparation method of the blood perfusion adsorbent with low protein adsorption property as described in the technical scheme, comprising the following steps:

[0059] (1) mixing styrene monomers, vinyl silicone oil monomers, a pore-forming agent and an oily initiator to obtain an oil phase;

[0060] (2) dissolving a dispersing agent in water to obtain an aqueous phase;

[0061] (3) mixing the oil phase obtained in the step (1) and the aqueous phase obtained in the step (2) to perform a suspension polymerization reaction, thereby obtaining a cross-linked silicone oil modified adsorption resin.

[0062] The application mixes styrene monomers, vinyl silicone oil monomers, a pore-forming agent and an oily initiator to obtain an oil phase.

[0063] In the application, the types and amounts of the styrene monomers, the vinyl silicone oil monomers, the pore-forming agent and the oily initiator are the same as those in the above technical scheme, which will not be repeated here.

[0064] The application does not have special limitations on the method for mixing the styrene monomers, the vinyl silicone oil monomers, the pore-forming agent and the oily initiator, and a conventional mixing method can be used to dissolve the above components. In the embodiments of the application, the method for mixing the styrene monomers, the vinyl silicone oil monomers, the pore-forming agent and the oily initiator can be stirring.

[0065] The application dissolves a dispersing agent in water to obtain an aqueous phase.

[0066] In the application, the type of the dispersing agent is the same as that in the above technical scheme, which will not be repeated here.

[0067] The application does not have special limitations on the method for dissolving the dispersing agent in water, and the dispersing agent can be completely dissolved in water.

[0068] After obtaining the oil phase and the aqueous phase, the application mixes the oil phase and the aqueous phase to perform a suspension polymerization reaction, thereby obtaining a cross-linked silicone oil modified adsorption resin.

[0069] The application does not have special limitations on the method for mixing the oil phase and the aqueous phase, and the two can be uniformly mixed to form a uniformly dispersed emulsion.

[0070] In the application, the temperature of the suspension polymerization reaction is preferably 20-90°C, and more preferably 75-80°C; and the reaction time of the suspension polymerization reaction is preferably 1-24h, and more preferably 12-24h. Controlling the temperature and the time in the above ranges is more conducive to promoting the suspension polymerization reaction to proceed fully.

[0071] The crosslinked silicone oil modified adsorption resin is obtained by purifying and drying the product obtained from the suspension polymerization reaction.

[0072] In another aspect of the present application, the method for preparing the blood perfusion adsorbent with low protein adsorption includes mixing the crosslinked silicone oil modified adsorption resin, an external crosslinking agent, a solvent and a catalyst, and sequentially performing crosslinking reaction to obtain the ultra-high crosslinked silicone oil modified adsorption resin.

[0073] In the present application, the types and amounts of the crosslinked silicone oil modified adsorption resin, the external crosslinking agent, the solvent and the catalyst are the same as those in the above technical solution, which will not be described here.

[0074] In the present application, the method for mixing the crosslinked silicone oil modified adsorption resin, the external crosslinking agent and the solvent is preferably standing at room temperature, and then mixing with the catalyst. By standing at room temperature, the crosslinked silicone oil modified adsorption resin can be fully swollen and uniformly mixed with other components. In the embodiments of the present application, the standing time can be 12 h.

[0075] In the present application, the temperature of the crosslinking reaction is preferably 40-130℃, more preferably 60-80℃, and the time of the crosslinking reaction is preferably 3-12 h. In the present application, the method for the crosslinking reaction temperature is preferably refluxing at the crosslinking reaction temperature. By performing the crosslinking reaction under the above conditions, the crosslinked silicone oil modified adsorption resin can be further crosslinked.

[0076] The ultra-high crosslinked silicone oil modified adsorption resin is obtained by purifying and drying the product obtained from the crosslinking reaction. The method for the purification and drying is not particularly limited in the present application, and any conventional purification and drying method can be used as long as the impurities in the product obtained from the crosslinking reaction are sufficiently removed.

[0077] The method provided by the present application is simple and convenient, and the structure and performance are controllable, so that the adsorbent with low protein adsorption amount, good hemocompatibility and good adsorption performance for different toxins can be obtained.

[0078] The present application also provides a blood perfusion device, wherein the adsorbent of the blood perfusion device is the blood perfusion adsorbent with low protein adsorption or the blood perfusion adsorbent with low protein adsorption prepared by the method.

[0079] In the present application, the blood perfusion adsorbent can be used for removing endogenous or exogenous toxicants or pathogenic substances in blood. The blood perfusion adsorbent of the present application has low protein adsorption, good blood compatibility and good adsorption performance for different toxicants, and can have adsorption and removal of uremic toxins (uremic macromolecular toxins, uremic protein-bound toxins, etc.), bilirubin and other liver failure-related toxins, bacterial toxins, inflammatory mediators, autoantibodies and immune complexes, high-lipid proteins, etc.

[0080] The technical solutions in the present application will be clearly and completely described below in combination with the embodiments in the present application. Obviously, the described embodiments are only some of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative work fall within the protection scope of the present application.

[0081] Embodiment 1

[0082] A low-protein-adsorption blood perfusion adsorbent, which 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 a water phase; the oil phase is composed of a styrene monomer (divinyl benzene), a vinyl silicone monomer (vinyl-terminated polydimethylsiloxane, Jiangsu Keqi V-20, viscosity about 5 cSt, molecular weight about 800), a pore former (toluene and methyl isobutyl carbinol), and an oily initiator (benzoyl peroxide BPO); the water phase is composed of a dispersant (gelatin) and water;

[0084] The mass ratio of the styrene monomer, the vinyl silicone monomer, the pore former and the oily initiator is 1:0.01:1.005:0.015; the mass ratio of the water and the 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 low-protein-adsorption blood perfusion adsorbent is as follows:

[0086] (1) 100 g of divinyl benzene (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 are mixed and dissolved uniformly to obtain an oil phase;

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

[0088] (3) the oil phase is added into the water phase, and a suspension polymerization reaction is carried out at 79℃ for 12h; after the reaction is completed, purification and post-treatment are carried out, and a cross-linked silicone oil modified adsorption resin, i.e. the blood perfusion adsorbent with low protein adsorption, is obtained.

[0089] The SEM images of the blood perfusion adsorbent with low protein adsorption prepared in the embodiment under different scales are shown in Figure 1 and 2 . In Figure 1 , the scale is 1μm, and in Figure 2 , the scale is 500nm. It can be seen from Figure 1 that the blood perfusion adsorbent with low protein adsorption prepared in the embodiment is a regular spherical white ball, and the appearance surface of the ball is smooth. It can be seen from Figure 2 that the micro surface of the blood perfusion adsorbent with low protein adsorption prepared in the embodiment has obvious pore structure.

[0090] The infrared spectrum of the blood perfusion adsorbent with low protein adsorption prepared in the embodiment is shown in Figure 3 . It can be seen from Figure 3 that the asymmetric stretching vibration of Si-O-Si appears at 1100cm -1 , and the symmetric stretching vibration of the silicon-oxygen-silicon bond appears at 800-850cm -1 . Thus, it can be illustrated that the vinyl silicone oil is successfully copolymerized to the molecular structure of the material.

[0091] Example 2

[0092] A blood perfusion adsorbent with low protein adsorption, which 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 a water phase; the oil phase is composed of a styrene monomer (divinyl benzene), a vinyl silicone oil monomer (vinyl-terminated polydimethylsiloxane, Jiangsu Keqi V-20, viscosity about 5cst, molecular weight about 800), a pore former (toluene, methyl isobutyl carbinol and methyl silicone oil) and an oily initiator (BPO); the water phase is composed of a dispersant (gelatin) and water;

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

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

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

[0097] (2) 600g water and 10g gelatin were mixed and dissolved uniformly to obtain an aqueous phase;

[0098] (3) The oil phase was added to the aqueous phase, and suspension polymerization was carried out at 78℃ for 24h; after the reaction was completed, purification and post-treatment were carried out to obtain a cross-linked silicone oil modified adsorption resin, which was a blood perfusion adsorbent with low protein adsorption.

[0099] Example 3

[0100] A 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, viscosity about 20cst, molecular weight about 2000), a pore former (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, the vinyl silicone oil monomer, the pore former, and the oily initiator is 1:0.001:1.5:0.02; the mass ratio of the water and the dispersant is 1:0.001; the mass ratio of the oil phase and the aqueous phase is 1:2;

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

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

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

[0106] (3) The oil phase was added to the aqueous phase, and suspension polymerization was carried out at 80℃ for 12h; after the reaction was completed, purification and post-treatment were carried out to obtain a cross-linked silicone oil modified adsorption resin, which was a blood perfusion adsorbent with low protein adsorption.

[0107] Example 4

[0108] A low-protein-adsorption hemoperfusion adsorbent 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 a water phase; the oil phase is composed of styrene monomers (divinylbenzene and styrene), vinyl silicone oil monomers (Shanghai Yandi SHYH-VI401, viscosity about 20cst, molecular weight about 2000), a pore former (isopropanol), and an oily initiator (azobisisobutyronitrile AIBN); the water phase is composed of a dispersant (polyvinyl alcohol 1788) and water;

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

[0111] The preparation method of the low-protein-adsorption hemoperfusion adsorbent is as follows:

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

[0113] (2) 800g water and 24g polyvinyl alcohol 1788 are mixed and dissolved uniformly to obtain a water phase;

[0114] (3) The oil phase is added to the water phase, and suspension polymerization is carried out at 70℃ for 24h; after the reaction is completed, purification and post-treatment are carried out to obtain the cross-linked silicone oil modified adsorption resin, i.e., the low-protein-adsorption hemoperfusion adsorbent.

[0115] The SEM images of the low-protein-adsorption hemoperfusion adsorbent prepared in this example under different scales are shown in Figure 4 and 5 In Figure 4 , the scale is 1μm, and in Figure 5 , the scale is 500nm. As can be seen from Figure 4 , the low-protein-adsorption hemoperfusion adsorbent prepared in this example is a white spherical regular sphere with a matte property. As can be seen from Figure 5 , the low-protein-adsorption hemoperfusion adsorbent prepared in this example has a clear pore structure in the microscopic surface.

[0116] Example 5

[0117] A low-protein-adsorption hemoperfusion adsorbent is an ultrahigh cross-linked silicone oil modified adsorption resin;

[0118] The super-high crosslinking silicone oil modified adsorption resin is prepared by mixing the crosslinking type silicone oil modified adsorption resin prepared in Example 1, an external crosslinking agent (triethyl orthoformate), a solvent (dichloroethane) and a catalyst (ferric chloride), and is prepared through a crosslinking reaction.

[0119] The preparation method of the low-protein adsorption blood perfusion adsorbent is as follows: 50 g of the crosslinking type silicone oil modified adsorption resin prepared in Example 1 is mixed with 1000 g of dichloroethane and 40 g of triethyl orthoformate, and after swelling at room temperature for 12 h, 25 g of ferric chloride is added and mixed, and reflux reaction is carried out at a gradient temperature of 80 DEG C for 12 h, and then purification is carried out, to obtain a super-high crosslinking silicone oil modified adsorption resin, which is a low-protein adsorption blood perfusion adsorbent.

[0120] Example 6

[0121] A low-protein adsorption blood perfusion adsorbent, which is a super-high crosslinking silicone oil modified adsorption resin.

[0122] The super-high crosslinking silicone oil modified adsorption resin is prepared by mixing the crosslinking type silicone oil modified adsorption resin prepared in Example 2, an external crosslinking agent (dimethyl acetal), a solvent (dichloroethane) and a catalyst (ferric chloride), and is prepared through a crosslinking reaction.

[0123] The preparation method of the low-protein adsorption blood perfusion adsorbent is as follows: 50 g of the crosslinking type silicone oil modified adsorption resin prepared in Example 2 is mixed with 1500 g of dichloroethane and 50 g of dimethyl acetal, and after swelling at room temperature for 12 h, 40 g of ferric chloride is added and mixed, and reflux reaction is carried out at a gradient temperature of 78 DEG C for 48 h, and then purification is carried out, to obtain a super-high crosslinking silicone oil modified adsorption resin, which is a low-protein adsorption blood perfusion adsorbent.

[0124] Example 7

[0125] A low-protein adsorption blood perfusion adsorbent, which is a super-high crosslinking silicone oil modified adsorption resin.

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

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

[0128] Example 8

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

[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) and then through cross-linking reaction;

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

[0132] Example 9

[0133] A low-protein adsorption blood perfusion adsorbent, which is an ultra-high 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 monomer (vinyl-terminated polydimethylsiloxane, Jiangsu Keqi V-20, viscosity about 5 cSt, molecular weight about 800), a pore-forming agent (toluene and methyl isobutyl carbinol) and an oil initiator (benzoyl peroxide BPO); the aqueous phase is composed of a dispersant (gelatin) and water;

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

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

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

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

[0139] (3) The oil phase was added to the aqueous phase, and suspension polymerization was carried out at 79°C for 12h; after the reaction was completed, purification and post-treatment were carried out to obtain a cross-linked silicone oil modified adsorption resin, i.e. 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 shown in Figure 6 From Figure 6 it can be seen that a higher content of vinyl silicone oil is used in this example, and the sample surface has no obvious pore structure.

[0141] Example 10

[0142] A blood perfusion adsorbent with low protein adsorption, which 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 monomer (vinyl-terminated polydimethylsiloxane, Jiangsu Keqi V-500, viscosity about 150cst, molecular weight 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, the vinyl silicone monomer, the porogen, and the oily initiator is 1:0.05:1.005:0.015; the mass ratio of the water and the dispersant is 1:0.01875; the mass ratio of the oil phase and the aqueous phase is 1:3.2;

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

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

[0147] (2) 800g water and 15g 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 12h; after the reaction is completed, purification and post-treatment are carried out to obtain the cross-linked silicone oil modified adsorption resin, i.e. the 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 shown in Figure 7 As can be seen from Figure 7 , the sample surface has no obvious pore structure.

[0150] Comparative Example 1

[0151] A preparation method of an adsorption composite material is as follows:

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

[0153] (2) 800g water and 15g gelatin are mixed and dissolved uniformly to obtain a water phase;

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

[0155] Comparative Example 2

[0156] A preparation method of an adsorption composite material is as follows: 50g of the cross-linked silicone oil modified adsorption resin prepared in Comparative Example 1 is mixed with 1000g dichloroethane and 40g triethyl orthoformate, and after swelling at room temperature for 12h, 25g of ferric chloride is added and mixed, and a reflux reaction is carried out at 80°C under gradient temperature conditions for 12h, and purification is carried out to obtain the super-high cross-linked adsorption resin.

[0157] Test Example

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

[0159] (1) Protein adsorption performance evaluation

[0160] The protein adsorption rate test method is as follows: the sample of the adsorbent to be tested is washed with normal saline for 5 times, and the sample after washing is taken for testing at a bath ratio of 1 mL / 10 mL. The sample is dynamically contacted with blood plasma at 170 r / min in an environment at 37°C for 120 min, the contents of albumin and total protein before and after adsorption are detected, and the adsorption rate is calculated to obtain the structure as shown in Table 1.

[0161] Table 1: Protein adsorption performance evaluation results of different samples of adsorbents to be tested

[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 1-10 of the application are all lower than 1%. Compared with Comparative Examples 1-2 and commercial resins, the protein adsorption rate of the examples of the application is significantly reduced. It can be seen that the introduction of the organic silicon component in the blood perfusion adsorbent with low protein adsorption can effectively improve the anti-protein adsorption performance of the resin.

[0165] (2) Adsorption performance evaluation

[0166] 10 mL of a plasma solution containing β2-microglobulin (β2-MG), interleukin 6 (IL-6), and indoxyl sulfate IS is respectively added to 1 mL of the adsorbent sample obtained in the above-mentioned adsorbent to be tested, and after oscillation at 37°C for 2 h, the changes of the adsorbed substances are respectively determined to obtain the results as shown in Table 2.

[0167] Table 2: Toxic substance adsorption performance of different samples of adsorbents to be tested

[0168]

[0169]

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

[0171] (3) Blood compatibility evaluation

[0172] The present application evaluates the blood compatibility of the to-be-tested adsorbent sample through 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; a lower value indicates better blood compatibility.

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

[0174] Table 3 Blood compatibility index evaluation and detection results of different to-be-tested adsorbent samples

[0175] Hemolysis rate (%) Platelet drop 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 Control Example 1 1.8 18.4 Control Example 2 1.2 16.9 HA 130 resin 3.2 19.6

[0176] As shown in Table 3, the hemolysis rate of the low-protein-adsorption hemoperfusion adsorbents obtained using Examples 1-10 of the present invention is ≤0.1%, and the platelet-decreasing rate is less than 6%. Compared with Control Examples 1-2 and HA130 resin, the low-protein-adsorption hemoperfusion adsorbents provided in the embodiments of the present invention exhibit better blood compatibility. Furthermore, the biocompatibility of the low-protein-adsorption hemoperfusion adsorbents of Examples 1-10 of the present invention was tested for cytotoxicity, thrombosis, coagulation, complement activation, and immunogenicity, all showing excellent blood compatibility results.

[0177] The above results show that the low-protein adsorption hemoperfusion adsorbent provided by this invention maintains a high adsorption rate for β2-microglobulin (β2-MG) and interleukin IL-6; it also exhibits good adsorption performance for the protein-bound toxoid indophenol sulfate (IS); furthermore, the low-protein adsorption hemoperfusion adsorbent provided by this invention has a hemolysis rate ≤0.1% and a platelet count decrease rate of less than 6%, demonstrating good blood compatibility. Therefore, it can be used as an adsorbent in hemoperfusion devices.

[0178] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. The application of a low-protein-adsorption adsorbent in hemoperfusion, wherein the low-protein-adsorption adsorbent comprises a cross-linked silicone oil modified adsorbent resin or an ultra-high cross-linked silicone oil modified adsorbent 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 styrene monomers, vinyl silicone oil monomers, pore-forming agents, and oily initiators; the aqueous phase includes dispersants and water. The ultra-high crosslinked silicone oil modified adsorption resin is prepared by mixing the crosslinked silicone oil modified adsorption resin, external crosslinking agent, solvent and catalyst through a crosslinking reaction; The viscosity of the vinyl silicone oil is 5~100cs; the average molecular weight of the vinyl silicone oil is 400~5000.

2. The application according to claim 1, characterized in that, The vinyl silicone oil monomer includes at least one of single-terminal vinyl silicone oil, double-terminal vinyl silicone oil, and side-chain vinyl silicone oil.

3. The application according to claim 1, characterized in that, The styrene monomers include polyvinyl aromatic monomers and / or monovinyl aromatic monomers.

4. The application according to claim 1, characterized in that, The mass ratio of the styrene monomer, vinyl silicone oil monomer, pore-forming agent, and 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).

5. The application according to claim 1, characterized in that, The mass ratio of the cross-linked silicone oil modified adsorption resin, external cross-linking agent, solvent and catalyst is 1:(0.01~3):(1~40):(0.01~3).

6. The application according to claim 4, characterized in that, The mass ratio of the cross-linked silicone oil modified adsorption resin, external cross-linking agent, solvent and catalyst is 1:(0.01~3):(1~40):(0.01~3).

7. The application according to claim 1, characterized in that, The external crosslinking agent includes 4-aminobutyraldehyde dimethyl acetal, aminoacetaldehyde dimethyl acetal, aminoacetaldehyde diethanol, methylaminoacetaldehyde dimethyl acetal, N,N-dimethylformamide dimethyl acetal, N,N-dimethylformamide diethyl acetal, N,N-dimethylformamide diisopropyl acetal, ethoxyacetaldehyde diethanol, 4,4-(dimethylamino)butyraldehyde diethyl acetal, (S)-2-hydroxypropanaldehyde dimethoxyacetaldehyde, succinal bis(dimethyl acetal), and ethoxyacetaldehyde diethyl acetal. At least one of the following: aldehyde, acetaldehyde diacetate, butyraldehyde diacetate, nonanaldehyde dimethyl acetate, citral dimethyl acetate, benzaldehyde diacetate, isobutyraldehyde diethyl acetate, 2-chloroacetaldehyde diacetate, benzaldehyde dimethyl acetate, acrolein dimethyl acetate, propionaldehyde diethyl acetate, phenylacetaldehyde dimethyl acetate, 1,1,3,3-tetraethoxypropane, 1,1,3,3-tetramethoxypropane, triethyl orthoformate, trimethyl orthoformate, formaldehyde dimethyl acetate, and acetaldehyde diacetate.

8. The application according to any one of claims 1 to 7, characterized in that, The method for preparing the adsorbent with low protein adsorption capacity includes the following steps: (1) Styrene monomers, vinyl silicone oil monomers, pore-forming agents and oily initiators are mixed to obtain an oil phase; (2) Dissolve the dispersant in water to obtain an aqueous phase; (3) The oil phase obtained in step (1) and the aqueous phase obtained in step (2) are mixed and subjected to suspension polymerization to obtain cross-linked silicone oil modified adsorption resin. Alternatively, cross-linked silicone oil modified adsorption resin, external cross-linking agent, solvent and catalyst are mixed and cross-linking reaction is carried out in sequence to obtain ultra-high cross-linked silicone oil modified adsorption resin.

9. The application according to claim 8, characterized in that, The temperature of the suspension polymerization reaction in step (3) is 20~90℃, and the reaction time is 1~24h.

10. A blood perfusion device, wherein the adsorbent in the blood perfusion device is the cross-linked silicone oil modified adsorbent resin or the ultra-high cross-linked silicone oil modified adsorbent resin as described in any one of claims 1 to 9.

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