CN119114033A - A blood perfusion adsorbent with low protein adsorption, a preparation method thereof, and a blood perfusion device - Google Patents
A blood perfusion adsorbent with low protein adsorption, a preparation method thereof, and a blood perfusion device Download PDFInfo
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- CN119114033A CN119114033A CN202411501042.3A CN202411501042A CN119114033A CN 119114033 A CN119114033 A CN 119114033A CN 202411501042 A CN202411501042 A CN 202411501042A CN 119114033 A CN119114033 A CN 119114033A
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- silicone oil
- cross
- adsorbent
- blood perfusion
- adsorption
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- 239000003440 toxic substance Substances 0.000 description 1
- 208000009852 uremia Diseases 0.000 description 1
- 239000002441 uremic toxin Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
- B01J20/26—Synthetic macromolecular compounds
- B01J20/265—Synthetic macromolecular compounds modified or post-treated polymers
- B01J20/267—Cross-linked polymers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3679—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by absorption
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- Chemical & Material Sciences (AREA)
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- Heart & Thoracic Surgery (AREA)
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- Biomedical Technology (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Anesthesiology (AREA)
- Veterinary Medicine (AREA)
- Cardiology (AREA)
- Analytical Chemistry (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Abstract
The invention provides a low-protein-adsorptivity blood perfusion adsorbent, a preparation method thereof and a blood perfusion device, and belongs to the technical field of blood purification adsorbents. According to the preparation method, vinyl silicone oil is introduced into the adsorbent, the vinyl silicone oil has low surface energy and excellent protein adsorption resistance and tissue and blood compatibility, and the surface of the cross-linked silicone oil modified adsorption resin prepared by suspension polymerization has a pore structure, so that the adsorbent has better blood compatibility, middle and large molecular toxin adsorption performance and protein adsorption resistance, and the ultra-high cross-linked silicone oil modified adsorption resin can still maintain the protein adsorption resistance after the cross-linked silicone oil modified adsorption resin is subjected to further cross-linking reaction.
Description
Technical Field
The invention relates to the technical field of blood purification adsorbents, in particular to a low-protein-adsorptivity blood perfusion adsorbent, a preparation method thereof and a blood perfusion device.
Background
The blood perfusion adsorbent can remove pollutants by nonspecific or specific adsorption of poison, medicine and metabolite, thereby achieving the purpose of purifying blood. At present, common adsorbents used for blood perfusion adsorbents comprise active carbon, resin and the like, and the materials can effectively adsorb and remove toxic substances, metabolites, immune complexes and other harmful substances in blood, and have wide application in the fields of kidney diseases, liver diseases, immune diseases, excessive drugs, critical diseases and the like.
However, it has been found in clinical treatment and scientific experiments that the above-mentioned adsorbents generally have a problem of large protein adsorption amount. When the adsorption amount of the adsorbent to the protein is large, there are problems in that firstly, the adsorbent material is covered with a large amount of the protein to lower the adsorption efficiency to the target substance, secondly, the adsorption amount of the adsorbent protein is large to cause deterioration of the blood compatibility of the adsorbent, and thirdly, loss of the protein in blood or plasma adversely affects the body of the patient. Meanwhile, the materials generally have the problems of poor target toxin adsorption capacity, poor blood compatibility and the like.
Therefore, how to obtain the adsorbent with low protein adsorption quantity, good blood compatibility and good adsorption performance on different toxins is a technical problem to be solved in the field of the current blood perfusion adsorbent materials.
Disclosure of Invention
The invention aims to provide a low-protein adsorption blood perfusion adsorbent, a preparation method thereof and a blood perfusion device, the low-protein-adsorptivity blood perfusion adsorbent provided by the invention has low adsorption quantity of protein, good blood compatibility and excellent adsorption performance on different toxins.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a low-protein-adsorptivity blood perfusion adsorbent, which comprises cross-linked silicone oil modified adsorption resin or ultra-high cross-linked silicone oil modified adsorption resin;
The cross-linked silicone oil modified adsorption resin is prepared from an oil phase and a water phase through suspension polymerization, wherein the oil phase comprises a styrene monomer, a vinyl silicone oil monomer, a pore-forming agent and an oily initiator;
The ultra-high crosslinking silicone oil modified adsorption resin is prepared by mixing the crosslinking silicone oil modified adsorption resin, an external crosslinking agent, a solvent and a catalyst and performing crosslinking reaction.
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.
Preferably, the vinyl silicone oil monomer includes 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-functional vinyl silicone oil.
Preferably, the styrenic monomer comprises a polyvinyl aromatic monomer and/or a monovinyl aromatic monomer.
Preferably, the mass ratio of the styrene monomer to the vinyl silicone oil monomer to the pore-forming agent to the oily initiator is 1 (0.001-0.01): 0.3-3): 0.001-0.1;
The mass ratio of the water to the dispersing agent is 1 (0.0001-0.1);
the mass ratio of the oil phase to the water phase is 1 (1-5).
Preferably, the mass ratio of the cross-linked silicone oil modified adsorption resin to the external cross-linking agent to the solvent to the catalyst is 1 (0.01-3): 1-40): 0.01-3.
Preferably, the external cross-linking agent comprises 4-aminobutyraldehyde dimethyl acetal, aminoacetaldehyde diethyl acetal, methylaminoacetaldehyde dimethyl acetal, N-dimethylformamide dimethyl acetal, N, at least one of N-dimethylformamide diisopropylacetal, glycolaldehyde diethylacetal, 4- (dimethylamino) butanal diacetal, (S) -2-hydroxypropanal dimethoxyacetal, succinaldehyde bis (dimethylacetal), ethoxyacetaldehyde diethyl acetal, acetaldehyde diethyl acetal, butanal diacetal, nonanal dimethylacetal, citral dimethylacetal, benzaldehyde diethyl acetal, isobutyraldehyde diethyl acetal, 2-chloroacetal dimethanol, benzaldehyde dimethylacetal, acrolein dimethyl acetal, propionaldehyde diethyl acetal, phenylacetaldehyde dimethyl acetal, 1, 3-tetraethoxypropane, 1, 3-tetramethoxypropane, triethyl orthoformate, trimethyl orthoformate, formaldehyde dimethylacetal and acetaldehyde dimethyl acetal.
The invention also provides a preparation method of the low-protein-adsorptivity hemoperfusion adsorbent, which comprises the following steps:
(1) Mixing a styrene monomer, a vinyl silicone oil monomer, a pore-forming agent and an oily initiator to obtain an oil phase;
(2) Dissolving a dispersing agent in water to obtain a water phase;
(3) Mixing the oil phase obtained in the step (1) with the water phase obtained in the step (2) to perform suspension polymerization reaction to obtain the cross-linked silicone oil modified adsorption resin;
Or mixing the cross-linked silicone oil modified adsorption resin, an external cross-linking agent, a solvent and a catalyst, and sequentially carrying out cross-linking reaction to obtain the 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 low-protein adsorption blood perfusion adsorbent.
Preferably, the temperature of the suspension polymerization reaction in the step (3) is 20-90 ℃, and the reaction time of the suspension polymerization reaction is 1-24 hours.
The invention also provides a blood perfusion device, and the adsorbent of the blood perfusion device is the low-protein-adsorptivity blood perfusion adsorbent according to the technical scheme or the low-protein-adsorptivity blood perfusion adsorbent prepared by the preparation method according to the technical scheme.
The invention provides a low-protein-adsorptivity blood perfusion adsorbent which comprises cross-linked silicone oil modified adsorption resin or ultrahigh cross-linked silicone oil modified adsorption resin, wherein the cross-linked silicone oil modified adsorption resin is prepared by suspension polymerization of an oil phase and a water phase, the oil phase comprises a styrene monomer, a vinyl silicone oil monomer, a pore-forming agent and an oily initiator, the water phase comprises a dispersing agent and water, and the ultrahigh 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 and performing cross-linking reaction. According to the preparation method, vinyl silicone oil is introduced into the adsorbent, the vinyl silicone oil has low surface energy and excellent protein adsorption resistance and tissue and blood compatibility, and the surface of the cross-linked silicone oil modified adsorption resin prepared by suspension polymerization has a pore structure, so that the adsorbent has better blood compatibility, middle and large molecular toxin adsorption performance and protein adsorption resistance, and the ultra-high cross-linked silicone oil modified adsorption resin can still maintain the protein adsorption resistance after the cross-linked silicone oil modified adsorption resin is subjected to further cross-linking reaction. The results of the examples show that the low-protein-adsorptivity blood perfusion adsorbent provided by the invention has higher adsorption rate to beta 2-microglobulin (beta 2-MG) and interleukin IL-6, has better adsorption performance to protein-bound toxoid indoxyl sulfate IS, has hemolysis rate less than or equal to 0.1% and platelet reduction rate less than 6%, and shows better blood compatibility.
Drawings
FIG. 1 is a SEM image of the low protein adsorption hemoperfusion adsorbent prepared in example 1 of the present invention, scale 1 μm;
FIG. 2 is a SEM image of the low protein adsorption hemoperfusion adsorbent prepared in example 1 of the present invention, scale 500 nm;
FIG. 3 is an infrared spectrum of a low protein adsorption hemoperfusion adsorbent prepared in example 1 of the present invention;
FIG. 4 is a SEM image of the low protein adsorption hemoperfusion adsorbent prepared in example 4 of the present invention, scale 1 μm;
FIG. 5 is a SEM image of the low protein adsorption hemoperfusion adsorbent prepared in example 4 of the present invention, scale 500 nm;
FIG. 6 is an SEM image of a low protein adsorption hemoperfusion adsorbent prepared according to example 9 of the present invention;
FIG. 7 is an SEM image of a low protein adsorption hemoperfusion adsorbent prepared according to example 10 of the present invention.
Detailed Description
The invention provides a low-protein-adsorptivity blood perfusion adsorbent, which comprises cross-linked silicone oil modified adsorption resin or ultra-high cross-linked silicone oil modified adsorption resin.
In the present invention, the raw materials used in the present invention are all derived from commercial products well known to those skilled in the art unless otherwise specified.
The low-protein adsorption blood perfusion adsorbent provided by the invention comprises cross-linked silicone oil modified adsorption resin.
In the invention, the cross-linked silicone oil modified adsorption resin is prepared from an oil phase and a water phase through suspension polymerization.
In the invention, 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 dispersing agent and water.
In the present invention, the styrene-based 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 m-divinylbenzene and p-divinylbenzene, trivinylbenzene, divinylbenzene, divinylxylene, divinylnaphthalene and derivatives thereof, more preferably m-divinylbenzene and/or p-divinylbenzene. In the present invention, the derivative is preferably a halide, more preferably chlorodivinylbenzene. In an embodiment of the present invention, the styrenic monomer may be divinylbenzene. The source of the divinylbenzene is not particularly limited, and the divinylbenzene can be obtained by using conventional commercial products. In the present invention, commercially available divinylbenzene belongs to a polyvinyl aromatic monomer, and generally has a purity of 55%, 63% or 80%. The purity of divinylbenzene employed in the examples of the present invention may be 55%, 63% or 80%.
In the present invention, the monovinylaromatic monomer preferably comprises styrene and a C 1～C4 alkyl-substituted styrene or a C 1～C4 alkyl-substituted styrene derivative. In the present invention, the C 1～C4 alkyl-substituted styrene preferably includes ethyl styrene, m-ethyl styrene and/or p-ethyl styrene, and the C 1～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-ethylstyrene and p-ethylstyrene, more preferably a mixture of m-ethylstyrene and p-ethylstyrene or a mixture composed of styrene, m-ethylstyrene and p-ethylstyrene. The proportion of each component in the mixture is not particularly limited, and the mixture can be adjusted according to the needs. The styrene monomer is used as one of the monomers of the adsorption resin, so that the low-protein adsorption blood perfusion adsorbent has better strength and toughness.
In the present invention, the viscosity of the vinyl silicone oil monomer is preferably 5 to 100cs, more preferably 5 to 50cs. In an embodiment of the present invention, the viscosity of the vinyl silicone oil monomer may be 5cs, 10cs, 20cs, or 50cs. In the present invention, the average molecular weight of the vinyl silicone oil is preferably 400 to 5000, more preferably 800 to 4000. The invention adopts the vinyl silicone oil monomer with the parameters, can prevent the viscosity of the vinyl silicone oil monomer from being too high, and can lead the pore structure on the surface of the adsorbent material to be unobvious although the obtained resin adsorbent can keep better protein adsorption resistance, thereby obviously losing the adsorption performance of the adsorbent on the macromolecular toxins. Therefore, the parameters of the vinyl silicone oil monomer are controlled in the range, so that the porous structure is formed on the surface of the cross-linked silicone oil modified adsorption resin, and the adsorption performance and the protein adsorption resistance of the cross-linked silicone oil modified adsorption resin are improved.
In the present invention, the vinyl silicone oil monomer preferably includes at least one of a single-terminal vinyl silicone oil, a double-terminal vinyl silicone oil, a side-chain vinyl silicone oil, and a polyfunctional vinyl silicone oil. In the invention, the single-end vinyl silicone oil has only one vinyl functional group and is positioned at one end of a molecular chain, the chemical formula of the single-end vinyl silicone oil is preferably CH 2＝CH-Si(R)2-O-[Si(R)2-O]n-Si(R)3, and R is preferably methyl or phenyl. In the invention, the double-end vinyl silicone oil contains two vinyl functional groups which are respectively positioned at two ends of a molecular chain, the chemical formula of the double-end vinyl silicone oil is preferably CH 2＝CH-Si(R)2-O-[Si(R)2-O]n-Si(R)2-CH＝CH2, and R is preferably methyl or phenyl. In the invention, the vinyl functional group of the side chain vinyl silicone oil is positioned 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, and the R is preferably methyl or phenyl. In the present invention, the polyfunctional vinyl silicone oil preferably comprises methyl vinyl polysiloxane having vinyl groups at both ends and the middle of the molecular chain, wherein the polyfunctional vinyl silicone oil has a plurality of (three or more) vinyl functional groups in the molecular chain. In embodiments of the present invention, the vinyl silicone oil monomer may be of the type Jiangsu Keqi V-20 or Shangyandi SHYH-VI401. The vinyl silicone oil monomer has proper viscosity, molecular weight and vinyl content, and is favorable to raising the adsorptivity of cross-linked silicone oil modified adsorbing resin to toxin and protein adsorptivity resistance.
In the present invention, the porogen preferably comprises at least one of benzene, toluene, xylene, ethylbenzene, methyl isobutyl carbinol, diisobutyl carbinol, isooctanol, naphthene, paraffin, methyl silicone oil and industrial white oil, more preferably one or more of benzene, toluene, xylene and isooctanol. The porous cross-linked silicone oil modified adsorption resin can be made to have porosity by using the pore-forming agent, so that the contact area of the resin and a substance to be adsorbed is increased, and the adsorption capacity of macromolecular toxins is improved. The pore size of the cross-linked silicone oil modified adsorption resin is not particularly limited, and the cross-linked silicone oil modified adsorption resin can be adjusted according to the amount of pore-forming agent used.
In the present invention, the oily initiator preferably includes a peroxide, preferably dibenzoyl peroxide, and/or an azo compound, preferably azobisisobutyronitrile. The oily initiator can initiate the polymerization reaction of the styrene monomer and the vinyl silicone oil monomer.
In the invention, the mass ratio of the styrene monomer, the vinyl silicone oil monomer, the pore-foaming agent and the oily initiator is preferably 1 (0.001-0.01): 0.3-3): 0.001-0.1, more preferably 1 (0.005-0.01): 0.8-2): 0.015-0.1. The invention can control the usage of each component in the above range, and can obtain the adsorbent material with better target toxin adsorption performance and low protein adsorption amount.
In the present invention, the aqueous phase includes a dispersant and water.
In the present invention, the dispersant preferably includes at least one of polyvinyl alcohol, gelatin, and cellulose derivatives. In an embodiment of the invention, the cellulose derivative may be polyvinyl alcohol (trade mark 1788), gelatin or hydroxypropyl methylcellulose. The dispersing agent is added, so that the components are more favorable for being fully and uniformly dispersed, and the uniformity of the resin is improved.
In the present invention, the ratio of the water to the dispersant is preferably 1 (0.0001 to 0.1), more preferably 1 (0.001 to 0.1), and still more preferably 1 (0.01 to 0.03). In embodiments of the invention, the ratio of the mass of water to dispersant may be 1:0.01875, 1:0.0167 or 1:0.03.
In the present invention, the ratio of the mass of the oil phase to the mass of the water phase is preferably 1 (1-5), more preferably 1 (3-5). In embodiments of the invention, the ratio of the mass of the oil phase to the mass of the water phase may be 1:2, 1:2.75, 1:3.2 or 1:4.48. The invention can obtain the cross-linked silicone oil modified adsorption resin with uniform particle size distribution and high quality by controlling the mass ratio of the oil phase to the water phase.
The low-protein adsorption blood perfusion adsorbent provided by the invention comprises an ultrahigh cross-linked silicone oil modified adsorption resin.
In the invention, the ultra-high crosslinking silicone oil modified adsorption resin is prepared by mixing crosslinking silicone oil modified adsorption resin, an external crosslinking agent, a solvent and a catalyst and performing crosslinking reaction.
In the present invention, the cross-linked silicone oil-modified adsorbent resin is the same as the cross-linked silicone oil-modified adsorbent resin described above.
In the present invention, the external crosslinking agent preferably includes 4-aminobutyraldehyde dimethyl acetal, aminoacetaldehyde diethyl acetal, methylaminoacetaldehyde dimethyl acetal, N-dimethylformamide dimethyl acetal, N, N-dimethylformamide diisopropylacetal, glycolaldehyde diethanol, 4- (dimethylamino) butanal diacetal, (S) -2-hydroxypropanal dimethoxyacetal, succinaldehyde bis (dimethyl acetal), ethoxyacetaldehyde diethyl acetal, acetaldehyde diethanol, butanal diacetal, nonanal dimethyl acetal, citral dimethyl acetal, benzaldehyde diethyl acetal, isobutyraldehyde diethyl acetal, 2-chloroacetal dimethanol, benzaldehyde dimethyl acetal, acrolein dimethyl acetal, propionaldehyde diethyl acetal, phenylacetaldehyde dimethyl acetal, 1, 3-tetraethoxypropane, 1, 3-tetramethoxypropane, triethyl orthoformate, trimethyl orthoformate, formaldehyde dimethyl acetal and acetaldehyde dimethyl acetal, more preferred are triethyl orthoformate, acetaldehyde dimethyl acetal, N-dimethylformamide diethyl acetal or aminoacetaldehyde dimethyl acetal. The invention utilizes the external crosslinking agent to further crosslink the crosslinked silicone oil modified adsorption resin to form the ultra-high crosslinked silicone oil modified adsorption resin.
In the present invention, the solvent preferably includes at least one of dichloroethane, dichloromethane, nitrobenzene, toluene, xylene and benzene, more preferably includes dichloroethane, nitrobenzene or toluene. The solvent is more favorable for fully swelling the cross-linked silicone oil modified adsorption resin, so that the cross-linked silicone oil modified adsorption resin is further promoted to be further cross-linked to form the ultra-high cross-linked silicone oil modified adsorption resin.
In the present invention, the catalyst preferably includes at least one of ferric chloride, aluminum trichloride, and zinc chloride, more preferably ferric chloride or aluminum trichloride. The catalyst is added, so that the crosslinking reaction can be catalyzed and promoted to be rapidly carried out.
In the 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)
According to the low-protein-adsorptivity blood perfusion adsorbent, vinyl silicone oil is introduced, so that the low-protein-adsorptivity blood perfusion adsorbent has low surface energy, excellent protein-resistance adsorption performance and tissue and blood compatibility, and the surface of the cross-linked silicone oil modified adsorption resin prepared by suspension polymerization has a pore structure, so that the adsorbent has better blood compatibility, middle and large molecular toxin adsorption performance and protein-resistance adsorption performance, and the ultra-high cross-linked silicone oil modified adsorption resin can be obtained after the cross-linked silicone oil modified adsorption resin is subjected to further cross-linking reaction, and the protein-resistance adsorption performance can be still maintained.
The invention also provides a preparation method of the low-protein-adsorptivity hemoperfusion adsorbent, which comprises the following steps:
(1) Mixing a styrene monomer, a vinyl silicone oil monomer, a pore-forming agent and an oily initiator to obtain an oil phase;
(2) Dissolving a dispersing agent in water to obtain a water phase;
(3) And (3) mixing the oil phase obtained in the step (1) and the water phase obtained in the step (2) and performing suspension polymerization reaction to obtain the cross-linked silicone oil modified adsorption resin.
The invention mixes the styrene monomer, vinyl silicone oil monomer, pore-forming agent and oily initiator to obtain oil phase.
In the present invention, the types and amounts of the styrene monomer, the vinyl silicone oil monomer, the porogen and the oily initiator are the same as those of the above technical solutions, and no description is given here.
The method for mixing the styrene monomer, the vinyl silicone oil monomer, the pore-foaming agent and the oily initiator is not particularly limited, and the components can be dissolved by adopting a conventional mixing method. In an embodiment of the present invention, the method of mixing the styrenic monomer, the vinyl silicone oil monomer, the porogen, and the oily initiator may be stirring.
The invention dissolves the dispersant in water to obtain water phase.
In the present invention, the types of the dispersing agents are the same as those of the dispersing agents in the above technical scheme, and the description thereof will not be repeated here.
The method of dissolving the dispersant in water is not particularly limited, and the dispersant can be completely dissolved in water.
After the oil phase and the water phase are obtained, the oil phase and the water phase are mixed and subjected to suspension polymerization reaction to obtain the cross-linked silicone oil modified adsorption resin.
The method for mixing the oil phase and the water phase is not particularly limited, and the oil phase and the water phase can be uniformly mixed to form uniformly dispersed emulsion.
In the invention, the temperature of the suspension polymerization reaction is preferably 20-90 ℃, more preferably 75-80 ℃, and the reaction time of the suspension polymerization reaction is preferably 1-24 hours, more preferably 12-24 hours. The invention controls the temperature and time in the above range, which is more favorable for promoting the suspension polymerization reaction to proceed fully.
In the invention, preferably, after suspension polymerization, the product obtained by the suspension polymerization is purified and dried to obtain the cross-linked silicone oil modified adsorption resin. The method for purifying and drying is not particularly limited, and conventional purification and drying methods are adopted to sufficiently remove impurities in the product obtained by suspension polymerization.
In another scheme of the invention, the preparation method of the low-protein-adsorptivity hemoperfusion adsorbent comprises the steps of mixing cross-linked silicone oil modified adsorption resin, an external cross-linking agent, a solvent and a catalyst, and sequentially carrying out cross-linking reaction to obtain the ultrahigh cross-linked silicone oil modified adsorption resin.
In the present invention, the types and the amounts of the cross-linked silicone oil modified adsorption resin, the external cross-linking agent, the solvent and the catalyst are the same as those of the above technical solutions, and no description is given here.
In the present invention, the method of mixing the crosslinked silicone oil-modified adsorbent resin, the external crosslinking agent and the solvent is preferably to stand at room temperature and then to mix with the catalyst. The invention can fully swell the cross-linked silicone oil modified adsorption resin by standing at room temperature and uniformly mix with other components. In an embodiment of the present invention, the time of the standing may be 12 hours.
In the invention, 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 invention, the method of crosslinking reaction temperature is preferably reflux at the crosslinking reaction temperature. The crosslinking reaction is carried out under the conditions, so that the crosslinking silicone oil modified adsorption resin is more beneficial to promoting further crosslinking.
The invention preferably purifies and dries the product obtained by the crosslinking reaction after the crosslinking reaction to obtain the ultra-high crosslinking silicone oil modified adsorption resin. The method for purifying and drying is not particularly limited, and conventional purifying and drying methods are adopted to sufficiently remove impurities in the product obtained by the crosslinking reaction.
The method provided by the invention is simple and convenient, has controllable structure and performance, and can obtain the adsorbent with low protein adsorption quantity, good blood compatibility and good adsorption performance on different toxins.
The invention also provides a blood perfusion device, and the adsorbent of the blood perfusion device is the low-protein-adsorptivity blood perfusion adsorbent according to the technical scheme or the low-protein-adsorptivity blood perfusion adsorbent prepared by the preparation method according to the technical scheme.
In the present invention, the blood perfusion adsorbent can be used to remove endogenous or exogenous toxins or pathogenic substances in the blood. The blood perfusion adsorbent has the advantages of low protein adsorption capacity, good blood compatibility and good adsorption performance on different toxins, and can adsorb and remove uremic toxins (macromolecular toxins in uremia, uremic protein-bound toxoids, and the like), bilirubin and other toxins related to liver failure, bacterial toxins, inflammatory mediators, autoantibodies, immune complexes, high lipoproteins, and the like.
The technical solutions of the present invention will be clearly and completely described in the following in connection with the embodiments of the present invention. It will be apparent that the described embodiments are only some, but not all, embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Example 1
A low-protein-adsorptivity blood perfusion adsorbent which is a cross-linked silicone oil modified adsorption resin;
The crosslinked silicone oil modified adsorption resin is prepared from an oil phase and a water phase through suspension polymerization, wherein the oil phase is prepared from a styrene monomer (divinylbenzene), a vinyl silicone oil monomer (vinyl-terminated polydimethylsiloxane, jiangsu Koch QiV-20, the viscosity is about 5cst, the molecular weight is about 800), a pore-forming agent (toluene and methyl isobutyl carbinol) and an oily initiator (benzoyl peroxide BPO), and the water phase is composed of a dispersing agent (gelatin) and water;
The mass ratio of the styrene monomer to the vinyl silicone oil monomer to the pore-forming agent to the oily initiator is 1:0.01:1.005:0.015, the mass ratio of the water to the dispersing agent is 1:0.01875, and the mass ratio of the oil phase to the water phase is 1:3.2;
the preparation method of the low-protein adsorption blood perfusion adsorbent comprises the following steps:
(1) 100g of divinylbenzene (63%), 1g of vinyl silicone oil, 100g of toluene, 50g of methyl isobutyl carbinol and 1.5g of benzoyl peroxide BPO are mixed and dissolved uniformly to obtain an oil phase;
(2) Uniformly mixing 800g of water and 15g of gelatin, and dissolving to obtain a water phase;
(3) Adding the oil phase into the water phase, carrying out suspension polymerization at 79 ℃ for 12h, and purifying and post-treating after the reaction is finished to obtain the cross-linked silicone oil modified adsorption resin, namely the low-protein adsorption blood perfusion adsorbent.
SEM images of the low protein adsorption hemoperfusion adsorbent prepared in this example under different scales are shown in fig. 1 and 2. In FIG. 1, the scale is 1 μm, and in FIG. 2, the scale is 500nm. As can be seen from FIG. 1, the low protein adsorption hemoperfusion adsorbent prepared in this example is a white spherical regular sphere with smooth surface. As can be seen from fig. 2, the low protein adsorption blood perfusion adsorbent prepared by the present invention has a remarkable pore structure on the microscopic surface.
The infrared spectrum of the low protein adsorption blood perfusion adsorbent prepared in this example is shown in fig. 3. As can be seen from FIG. 3, si-O-Si asymmetric stretching vibration occurs at 1100cm -1 and symmetric stretching vibration of silicon-oxygen bonds occurs at 800-850 cm -1, so that successful copolymerization of vinyl silicone oil onto the molecular structure of the material can be demonstrated.
Example 2
A low-protein-adsorptivity blood perfusion adsorbent which is a cross-linked silicone oil modified adsorption resin;
The crosslinked silicone oil modified adsorption resin is prepared from an oil phase and a water phase through suspension polymerization, wherein the oil phase is prepared from a styrene monomer (divinylbenzene), a vinyl silicone oil monomer (vinyl-terminated polydimethylsiloxane, jiangsu Koch QiV-20, the viscosity is about 5cst, the molecular weight is about 800), a pore-forming agent (toluene, methyl isobutyl methyl alcohol and methyl silicone oil) and an oily initiator (BPO), and the water phase is composed of a dispersing agent (gelatin) and water;
The mass ratio of the styrene monomer to the vinyl silicone oil monomer to the pore-forming agent to the oily initiator is 1:0.005:1.2:0.02, the mass ratio of the water to the dispersing agent is 1:0.0167, and the mass ratio of the oil phase to the water phase is 1:2.75;
the preparation method of the low-protein adsorption blood perfusion adsorbent comprises the following steps:
(1) 100g of divinylbenzene (80%), 0.5g of vinyl silicone oil, 80g of toluene, 20g of methyl isobutyl carbinol, 20g of methyl silicone oil (10 cst) and 20gBPO are mixed and dissolved uniformly to obtain an oil phase;
(2) Mixing 600g of water and 10g of gelatin, and uniformly dissolving to obtain a water phase;
(3) Adding the oil phase into the water phase, carrying out suspension polymerization at 78 ℃ for 24 hours, and purifying and post-treating after the reaction is finished to obtain the cross-linked silicone oil modified adsorption resin, namely the low-protein adsorption blood perfusion adsorbent.
Example 3
A low-protein-adsorptivity blood perfusion adsorbent which is a cross-linked silicone oil modified adsorption resin;
The crosslinked silicone oil modified adsorption resin is prepared from an oil phase and a water phase through suspension polymerization, wherein the oil phase is prepared from a styrene monomer (divinylbenzene), a vinyl silicone oil monomer (Shanghai Di SHYH-VI401, the viscosity is about 20cst, the molecular weight is about 2000, a pore-forming agent (toluene and methyl silicone oil) and an oily initiator (BPO), and the water phase is prepared from a dispersing agent (gelatin) and water;
The mass ratio of the styrene monomer to the vinyl silicone oil monomer to the pore-forming agent to the oily initiator is 1:0.001:1.5:0.02, the mass ratio of the water to the dispersing agent is 1:0.001, and the mass ratio of the oil phase to the water phase is 1:2;
the preparation method of the low-protein adsorption blood perfusion adsorbent comprises the following steps:
(1) Mixing and dissolving 100g of divinylbenzene (55%), 0.1g of vinyl silicone oil, 100g of toluene, 50g of methyl silicone oil and 2g of BPO uniformly to obtain an oil phase;
(2) Mixing 500g of water and 0.5g of hydroxypropyl methylcellulose, and dissolving uniformly to obtain a water phase;
(3) Adding the oil phase into the water phase, carrying out suspension polymerization at 80 ℃ for 12 hours, and purifying and post-treating after the reaction is finished to obtain the cross-linked silicone oil modified adsorption resin, namely the low-protein adsorption blood perfusion adsorbent.
Example 4
A low-protein-adsorptivity blood perfusion adsorbent which is a cross-linked silicone oil modified adsorption resin;
The crosslinked silicone oil modified adsorption resin is prepared from an oil phase and a water phase through suspension polymerization, wherein the oil phase is composed of styrene monomers (divinylbenzene and styrene), vinyl silicone oil monomers (Shanghai Di SHYH-VI401, the viscosity is about 20cst, the molecular weight is about 2000), a pore-forming agent (isopropanol) and an oily initiator (azodiisobutyronitrile AIBN), and the water phase is composed of a dispersing agent (polyvinyl alcohol 1788) and water;
The mass ratio of the styrene monomer to the vinyl silicone oil monomer to the pore-forming agent to the oily initiator is 1:0.001:0.8:0.03, the mass ratio of the water to the dispersing agent is 1:0.03, and the mass ratio of the oil phase to the water phase is 1:4.48;
the preparation method of the low-protein adsorption blood perfusion adsorbent comprises the following steps:
(1) 80g of divinylbenzene (55%), 20g of styrene, 1g of vinyl silicone oil, 80g of isopropanol and 3g of AIBN are uniformly mixed and dissolved to obtain an oil phase;
(2) Uniformly mixing 800g of water and 24g of polyvinyl alcohol 1788, and dissolving to obtain a water phase;
(3) Adding the oil phase into the water phase, carrying out suspension polymerization at 70 ℃ for 24 hours, and purifying and post-treating after the reaction is finished to obtain the cross-linked silicone oil modified adsorption resin, namely the low-protein adsorption blood perfusion adsorbent.
SEM images of the low protein adsorption hemoperfusion adsorbent prepared in this example under different scales are shown in fig. 4 and 5. In FIG. 4, the scale is 1 μm, and in FIG. 5, the scale is 500nm. As can be seen from fig. 4, the low protein adsorption hemoperfusion adsorbent prepared in this example is a white sphere, and has a matte property. As can be seen from fig. 5, the low protein adsorption blood perfusion adsorbent prepared by the present invention has a remarkable pore structure on the microscopic surface.
Example 5
A low-protein-adsorptivity blood perfusion adsorbent which is an ultrahigh cross-linked silicone oil modified adsorption resin;
The ultra-high crosslinking silicone oil modified adsorption resin is prepared by mixing the crosslinking silicone oil modified adsorption resin prepared in the embodiment 1, an external crosslinking agent (triethyl orthoformate), a solvent (dichloroethane) and a catalyst (ferric trichloride) and performing a crosslinking reaction;
The preparation method of the low-protein adsorption blood perfusion adsorbent comprises the steps of mixing 50g of the cross-linked silicone oil modified adsorption resin prepared in the embodiment 1 with 1000g of dichloroethane and 40g of triethyl orthoformate, swelling for 12 hours at room temperature, adding 25g of ferric trichloride, mixing, carrying out reflux reaction for 12 hours under the condition of 80 ℃ gradient heating, and purifying to obtain the ultra-high cross-linked silicone oil modified adsorption resin, namely the low-protein adsorption blood perfusion adsorbent.
Example 6
A low-protein-adsorptivity blood perfusion adsorbent which is an ultrahigh cross-linked silicone oil modified adsorption resin;
the ultra-high crosslinking silicone oil modified adsorption resin is prepared by mixing the crosslinking silicone oil modified adsorption resin prepared in the embodiment 2, an external crosslinking agent (acetaldehyde dimethyl acetal), a solvent (dichloroethane) and a catalyst (ferric trichloride) and performing a crosslinking reaction;
The preparation method of the low-protein adsorption blood perfusion adsorbent comprises the steps of mixing 50g of the cross-linked silicone oil modified adsorption resin prepared in the embodiment 2 with 1500g of dichloroethane and 50g of acetaldehyde dimethyl acetal, swelling for 12 hours at room temperature, adding 40g of ferric trichloride, mixing, carrying out reflux reaction for 48 hours under the condition of temperature gradient rise at 78 ℃, and purifying to obtain the ultra-high cross-linked silicone oil modified adsorption resin, namely the low-protein adsorption blood perfusion adsorbent.
Example 7
A low-protein-adsorptivity blood perfusion adsorbent which is an ultrahigh cross-linked silicone oil modified adsorption resin;
the ultra-high crosslinking silicone oil modified adsorption resin is prepared by mixing the crosslinking silicone oil modified adsorption resin prepared in the embodiment 3, an external crosslinking agent (N, N-dimethylformamide diethyl acetal), a solvent (nitrobenzene) and a catalyst (ferric trichloride) and carrying out a crosslinking reaction;
The preparation method of the low-protein adsorption blood perfusion adsorbent comprises the steps of mixing 50g of the cross-linked silicone oil modified adsorption resin prepared in the embodiment 3 with 500g of nitrobenzene and 50g of N, N-dimethylformamide diethyl acetal, swelling for 12 hours at room temperature, adding 100g of ferric trichloride, mixing, carrying out reflux reaction for 8 hours at the temperature of 80 ℃ in a gradient heating condition, and purifying to obtain the ultra-high cross-linked silicone oil modified adsorption resin, namely the low-protein adsorption blood perfusion adsorbent.
Example 8
A low-protein-adsorptivity blood perfusion adsorbent which is an ultrahigh cross-linked silicone oil modified adsorption resin;
The ultra-high crosslinking silicone oil modified adsorption resin is prepared by mixing the crosslinking silicone oil modified adsorption resin prepared in the embodiment 4, an external crosslinking agent (aminoacetaldehyde dimethyl acetal), a solvent (nitrobenzene) and a catalyst (aluminum trichloride) and performing a crosslinking reaction;
The preparation method of the low-protein adsorption blood perfusion adsorbent comprises the steps of mixing 50g of the cross-linked silicone oil modified adsorption resin prepared in the embodiment 4 with 750g of nitrobenzene and 25g of aminoacetaldehyde dimethyl acetal, swelling for 12 hours at room temperature, adding 2.5g of aluminum trichloride, mixing, carrying out reflux reaction for 3 hours under the condition of 60 ℃ gradient temperature rise, and purifying to obtain the ultra-high cross-linked silicone oil modified adsorption resin, namely the low-protein adsorption blood perfusion adsorbent.
Example 9
A low-protein-adsorptivity blood perfusion adsorbent which is a cross-linked silicone oil modified adsorption resin;
The crosslinked silicone oil modified adsorption resin is prepared from an oil phase and a water phase through suspension polymerization, wherein the oil phase is prepared from a styrene monomer (divinylbenzene), a vinyl silicone oil monomer (vinyl-terminated polydimethylsiloxane, jiangsu Koch QiV-20, the viscosity is about 5cst, the molecular weight is about 800), a pore-forming agent (toluene and methyl isobutyl carbinol) and an oily initiator (benzoyl peroxide BPO), and the water phase is composed of a dispersing agent (gelatin) and water;
The mass ratio of the styrene monomer to the vinyl silicone oil monomer to the pore-forming agent to the oily initiator is 1:0.05:1.005:0.015, the mass ratio of the water to the dispersing agent is 1:0.01875, and the mass ratio of the oil phase to the water phase is 1:3.2;
the preparation method of the low-protein adsorption blood perfusion adsorbent comprises the following steps:
(1) 100g of divinylbenzene (63%), 5g of vinyl silicone oil, 100g of toluene, 50g of methyl isobutyl carbinol and 1.5g of BPO are mixed and dissolved uniformly to obtain an oil phase;
(2) Uniformly mixing 800g of water and 15g of gelatin, and dissolving to obtain a water phase;
(3) Adding the oil phase into the water phase, carrying out suspension polymerization at 79 ℃ for 12h, and purifying and post-treating after the reaction is finished to obtain the cross-linked silicone oil modified adsorption resin, namely the low-protein adsorption blood perfusion adsorbent.
An SEM image of the low protein adsorption hemoperfusion adsorbent prepared in this example is shown in fig. 6. As can be seen from fig. 6, the sample surface has no obvious pore structure by using the vinyl silicone oil with higher content in this example.
Example 10
A low-protein-adsorptivity blood perfusion adsorbent which is a cross-linked silicone oil modified adsorption resin;
The crosslinked silicone oil modified adsorption resin is prepared from an oil phase and a water phase through suspension polymerization, wherein the oil phase is prepared from a styrene monomer (divinylbenzene), a vinyl silicone oil monomer (vinyl-terminated polydimethylsiloxane, jiangsu Koch QiV-500, the viscosity is about 150cst, the molecular weight is about 8000), a pore-forming agent (toluene and methyl isobutyl carbinol) and an oily initiator (benzoyl peroxide BPO), and the water phase is composed of a dispersing agent (gelatin) and water;
The mass ratio of the styrene monomer to the vinyl silicone oil monomer to the pore-forming agent to the oily initiator is 1:0.05:1.005:0.015, the mass ratio of the water to the dispersing agent is 1:0.01875, and the mass ratio of the oil phase to the water phase is 1:3.2;
the preparation method of the low-protein adsorption blood perfusion adsorbent comprises the following steps:
(1) 100g of divinylbenzene (63%), 5g of vinyl silicone oil, 100g of toluene, 50g of methyl isobutyl carbinol and 1.5g of BPO are mixed and dissolved uniformly to obtain an oil phase;
(2) Uniformly mixing 800g of water and 15g of gelatin, and dissolving to obtain a water phase;
(3) Adding the oil phase into the water phase, carrying out suspension polymerization at 79 ℃ for 12h, and purifying and post-treating after the reaction is finished to obtain the cross-linked silicone oil modified adsorption resin, namely the low-protein adsorption blood perfusion adsorbent.
SEM images of the low protein adsorption hemoperfusion adsorbent prepared in this example are shown in fig. 7. As can be seen from fig. 7, the present example uses vinyl silicone oil of higher viscosity, and the sample surface has no obvious pore structure.
Comparative example 1
The preparation method of the adsorption composite material comprises the following steps:
(1) 100g of divinylbenzene (63%), 100g of toluene, 50g of methyl isobutyl carbinol and 1.5g of benzoyl peroxide BPO are mixed and dissolved uniformly to obtain an oil phase;
(2) Uniformly mixing 800g of water and 15g of gelatin, and dissolving to obtain a water phase;
(3) Adding the oil phase into the water phase, carrying out suspension polymerization at 79 ℃ for 12h, and purifying and post-treating after the reaction is finished to obtain the crosslinked adsorption resin.
Comparative example 2
The preparation method of the adsorption composite material comprises the steps of mixing 50g of the cross-linked silicone oil modified adsorption resin prepared in the comparative example 1 with 1000g of dichloroethane and 40g of triethyl orthoformate, swelling for 12 hours at room temperature, adding 25g of ferric trichloride, mixing, carrying out reflux reaction for 12 hours at 80 ℃ under the gradient heating condition, and purifying to obtain the ultra-high cross-linked adsorption resin.
Test case
The adsorbents obtained in examples 1 to 10 and comparative examples 1 to 2 and the commercial perfusion resin CytoSorb TM adsorbent and the perfusion resin HA130 resin sample were used as the adsorbent samples to be tested, and protein adsorption performance evaluation, target toxin adsorption performance evaluation and related safety evaluation were performed in order.
(1) Evaluation of protein adsorption Performance
The protein adsorption rate test method comprises the steps of washing an adsorbent sample to be tested with physiological saline for 5 times, and taking the washed sample to test according to a bath ratio of 1mL/10 mL. The sample was dynamically contacted with plasma at 37℃for 120min at 170r/min, the albumin and total protein contents before and after adsorption were detected, and the adsorption rate was calculated to give the structure shown in Table 1.
TABLE 1 evaluation results of protein adsorption Performance of different adsorbent samples to be tested
As can be seen from Table 1, the adsorption rates of albumin and total protein of the low-protein adsorption blood perfusion adsorbents prepared in examples 1-10 of the present invention are all lower than 1%. Compared with comparative examples 1-2 and commercial resins, the protein adsorption rate of the examples of the present invention is significantly reduced. Therefore, the organic silicon component is introduced into the low-protein adsorption blood perfusion adsorbent, so that the protein adsorption resistance of the resin can be effectively improved.
(2) Evaluation of adsorption Performance
10ML of a plasma solution containing β2-microglobulin (β2-MG), interleukin 6 (IL-6) and indoxyl sulfate IS was taken and 1mL of the adsorption resin obtained by the above adsorbent sample to be tested was added, and after shaking at 37℃for 2 hours, the change of the adsorbed substances was measured, respectively, and the results were shown in Table 2.
TABLE 2 toxin adsorption Properties of different adsorbent samples to be tested
As can be seen from Table 2, the low protein adsorption blood perfusion adsorbents prepared in examples 1-8 of the invention all maintain higher adsorption rates of beta 2-microglobulin (beta 2-MG) and interleukin IL-6 and even are superior to HA130 resin, and in addition, the low protein adsorption blood perfusion adsorbents prepared in examples 7 and 8 have better adsorption performance on protein-bound toxoid indoxyl sulfate IS, which IS obviously superior to other HA130 resins due to the fact that amine groups introduced in the post-crosslinking process of the resins are related. The low protein adsorption hemoperfusion adsorbents prepared in examples 9-10 were significantly reduced in adsorption performance of macromolecular toxins, which was related to the insignificant pore structure of the adsorbent resin surface caused by the high content and high viscosity of vinyl silicone oil used in examples 9 and 10, respectively. Therefore, the property and the dosage of the vinyl silicone oil have direct influence on the surface pore structure and the adsorption performance of the resin adsorbent. And the vinyl silicone oil with the viscosity of 5-100 cs and the average molecular weight of 400-5000 is adopted, and the mass ratio of the vinyl silicone oil monomer to the styrene monomer is controlled to be (0.001-0.01): 1, so that the method is more beneficial to obtaining better middle and large molecular toxin performance and protein adsorption resistance.
(3) Evaluation of blood compatibility
The invention evaluates the blood compatibility of the adsorbent sample to be tested through the performance indexes such as the hemolysis rate, the platelet count test and the like. The hemolysis rate and the platelet decrease rate can directly reflect the good or bad of the blood compatibility of the material, and the lower value shows better blood compatibility.
The hemolysis rate test method comprises the steps of washing an adsorbent sample to be tested with physiological saline for 5 times, and taking the washed sample to test according to a bath ratio of 5g/10 mL. The sample is incubated with diluted rabbit blood at 37 ℃, absorbance of hemoglobin released by red blood cell disruption is detected, and the hemolysis rate is calculated. Platelet count test resin samples were washed 5 times with physiological saline and the washed samples were tested at a bath ratio of 0.2 g/ml. The sample was dynamically contacted with whole blood at 30r/min for 60min in a 37 ℃ environment, the number of platelets in the whole blood was detected using a blood cell analyzer, and the platelet drop rate was calculated. The results of the blood compatibility index evaluation test for the different adsorbent samples to be tested are shown in table 3 below.
TABLE 3 evaluation of blood compatibility index for different adsorbent samples to be tested
| 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 |
As can be seen from Table 3, the low protein adsorptivity blood perfusion adsorbents obtained in examples 1 to 10 and the like according to the embodiments of the present invention all had a hemolysis ratio of 0.1% or less and a platelet lowering ratio of 6% or less. Compared with comparative examples 1-2 and HA130 resin, the low protein adsorption hemoperfusion adsorbent provided by the embodiment of the invention HAs better blood compatibility. Meanwhile, the low protein adsorption hemoperfusion adsorbents of examples 1-10 of the present invention showed excellent results of blood compatibility by testing the biocompatibility such as cytotoxicity, thrombosis, coagulation, complement activation, immunity, etc.
The results show that the low-protein-adsorptivity blood perfusion adsorbent provided by the invention has higher adsorption rate to beta 2-microglobulin (beta 2-MG) and interleukin IL-6, has better adsorption performance to protein-bound toxoid indoxyl sulfate IS, has hemolysis rate less than or equal to 0.1 percent, has platelet reduction rate less than 6 percent, and shows better blood compatibility. It can be used as an adsorbent for a blood perfusion apparatus.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (10)
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