CN111135807A - High-mechanical-strength hydrophilic adsorbent for whole blood perfusion and preparation method thereof - Google Patents

High-mechanical-strength hydrophilic adsorbent for whole blood perfusion and preparation method thereof Download PDF

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CN111135807A
CN111135807A CN202010104295.2A CN202010104295A CN111135807A CN 111135807 A CN111135807 A CN 111135807A CN 202010104295 A CN202010104295 A CN 202010104295A CN 111135807 A CN111135807 A CN 111135807A
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adsorbent
acid
water
whole blood
blood perfusion
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刘云鸿
彭新艳
刘云晖
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    • 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
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Abstract

The invention provides a high-mechanical-strength hydrophilic adsorbent for whole blood perfusion and a preparation method thereof. The preparation method mainly comprises suspension polymerization and acid-base treatment, wherein the comonomer and the acrylonitrile monomer are subjected to cross-linking polymerization reaction and then subjected to acid-base treatment to obtain the high-mechanical-strength hydrophilic adsorbent for whole blood perfusion. The adsorbent has high mechanical strength, reduces particle damage and improves the use safety of the adsorbent resin; the adsorbent prepared by the invention has good hydrophilicity and high blood compatibility, and can be suitable for whole blood perfusion; the adsorbent prepared by the invention has excellent adsorption and removal performance on endogenous or exogenous toxicants or pathogenic substances in blood.

Description

High-mechanical-strength hydrophilic adsorbent for whole blood perfusion and preparation method thereof
Technical Field
The invention relates to an adsorbent and a preparation method thereof, in particular to a resin adsorbent which has high mechanical strength and hydrophilicity and can be used for whole blood perfusion and a preparation method thereof.
Background
The blood perfusion is a treatment technology for leading the blood of a patient to extracorporeal circulation by means of power, and removing endogenous or exogenous toxicants or pathogenic substances in the blood of the patient through an adsorbent with a special adsorption function in a blood perfusion device so as to achieve blood purification.
The preparation of the adsorbing material with good blood compatibility, high safety and good adsorption performance is the key point of the development of the blood perfusion technology. Currently, the commonly used adsorbent materials for blood perfusion mainly include activated carbon, natural modified polymers, synthetic polymers and inorganic materials. Wherein, the polymeric microsphere, such as the cross-linked polystyrene microsphere adsorbent, is widely applied to blood perfusion, the chemical stability of the adsorbent is good, the blood compatibility is good, and the physical and chemical structures of the adsorbent can be artificially controlled in the preparation process. However, the mechanical strength of polymeric microspheres, such as crosslinked polystyrene microsphere adsorbents, is not ideal enough, and on one hand, in the production process of the adsorbents and the hemoperfusion apparatus thereof, the production efficiency and cost are easily affected by the breakage of resin particles; on the other hand, during the transportation and transfer process and clinical use of the adsorbent-containing perfusion apparatus, resin particles may fall off, which affects the use safety of patients. In addition, since the cross-linked polymer microsphere adsorbent is hydrophobic, the blood compatibility of the material needs to be improved in the field of whole blood perfusion. On the premise of ensuring the performance of adsorbing blood purification, the mechanical strength and the hydrophilicity of the adsorbent are improved, and the safety and the blood compatibility of the material are improved, so that the method is a technical problem and direction of the existing hemoperfusion adsorption resin material.
Disclosure of Invention
In order to overcome the disadvantages and shortcomings of the prior art, the first objective of the present invention is to provide a crosslinked acrylonitrile-based copolymer microsphere adsorbent, which has high mechanical strength, good hydrophilicity and blood compatibility, and good broad-spectrum adsorption performance on endogenous or exogenous toxicants or pathogenic substances in blood.
The second purpose of the invention is to provide a preparation method of the crosslinking acrylonitrile-based copolymer microsphere adsorbent.
In order to realize the first object of the invention, the invention provides a high-mechanical-strength hydrophilic adsorbent for whole blood perfusion, which is a cross-linked acrylonitrile-based copolymer microsphere, and the cross-linked acrylonitrile-based copolymer microsphere has a porous cross-linked structure.
The adsorbent for whole blood perfusion is obtained by copolymerization and crosslinking of a comonomer and an acrylonitrile monomer and certain acid and alkali treatment. Wherein, acrylonitrile chain segment component is introduced into the traditional polymer microsphere material to improve the mechanical strength of the resin microsphere; the introduction of acrylonitrile in the adsorbent improves the hydrophilicity of the adsorbent material; in addition, during the acid treatment and alkali treatment processes of the preparation of the adsorbent, the cyano group of the acrylonitrile component in the adsorbent can be partially hydrolyzed to form carboxylic acid, amido, imido and other groups, so that the hydrophilicity of the adsorbent material can be further improved, and the blood compatibility of the material can be further improved; the cross-linked acrylonitrile-based copolymer microsphere adsorbent has a porous cross-linked structure and specific chemical groups, and can ensure better broad-spectrum adsorption performance while providing mechanical strength and hydrophilicity, wherein the adsorption performance comprises middle-large molecular toxins, charged protein combined toxins and the like.
The further technical proposal is that the particle size of the adsorbent for whole blood perfusion is in the range of 0.05mm to 3 mm.
When the high mechanical strength hydrophilic adsorbent for whole blood perfusion is in the above range, it has a high specific surface area, and can achieve a good adsorption effect without destroying blood components and affecting the flow of liquid.
In order to achieve the second object of the present invention, the present invention provides a method for preparing a high mechanical strength hydrophilic adsorbent for whole blood perfusion, comprising the steps of:
the method comprises the following steps: suspension polymerization comprises an oil phase consisting of a comonomer, acrylonitrile, a pore-forming agent and an oily initiator, wherein the oil phase is subjected to suspension polymerization in a water phase consisting of a dispersant and water, and the pore-forming agent in the resin obtained by polymerization is removed to obtain polymeric microspheres;
step two: acid-base treatment
And (3) placing the polymeric microspheres obtained in the step one in an acid solution consisting of inorganic acid and water for acid treatment, then placing in an alkali solution consisting of inorganic base and water for alkali treatment, and purifying to obtain the high-mechanical-strength hydrophilic adsorbent for whole blood perfusion.
The preparation method provided by the invention mainly comprises suspension polymerization and acid-base treatment. Wherein the suspension polymerization is a cross-linking polymerization reaction of a comonomer and an acrylonitrile monomer; the pore-foaming agent is used for forming a porous structure; in the system, the comonomer and the acrylonitrile monomer can form different component structures such as a comonomer high-molecular chain segment, a polyacrylonitrile chain segment, a comonomer-acrylonitrile copolymer chain segment and the like through crosslinking polymerization, the different component chain segment structures can form an internal microstructure due to phase separation, and a specific pore size distribution is formed under the combined action of a pore-foaming agent, so that the adsorption performance of the adsorbent is improved. The adsorbent is treated by acid and alkali, and part of cyano groups introduced by acrylonitrile monomers in the system can be hydrolyzed to form carboxylic acid, amido, imido and other groups, so that the hydrophilicity of the adsorbent material can be further improved, and the compatibility between the adsorbent and blood is further improved.
According to a further technical scheme, in the step one, the comonomer is vinylpyridine, methacryloyloxyethyltrimethyl ammonium chloride, styrene, methylstyrene, ethylstyrene, divinylbenzene, methyl acrylate, methyl methacrylate, ethyl acrylate, ethyl methacrylate, butyl acrylate, butyl methacrylate, isooctyl acrylate, acrylamide, isobutyl acrylate, lauryl methacrylate, isooctyl acrylate, tert-butyl acrylate, polyethylene glycol diacrylate, polyethylene glycol dimethacrylate, isobornyl acrylate, 1, 6-hexanediol diacrylate, glycerol trimethylolpropane triacrylate, polydipentaerythritol hexaacrylate, dipropylene glycol diacrylate, polyethylene glycol o-phenylphenyl ether acrylate, tripropylene glycol diacrylate, trimethylolpropane trimethacrylate, poly (t-butyl acrylate), poly (t-butyl, At least one of triethoxy trimethylolpropane triacrylate, tris (2-hydroxyethyl) isocyanurate triacrylate and 2-phenoxyethyl acrylate; the pore-foaming agent is at least one of toluene, xylene, ethyl acetate, butyl acetate, cyclohexane or methylcyclohexane; the oily initiator is at least one of benzoyl peroxide or azobisisobutyronitrile; the dispersing agent is at least one of polyvinyl alcohol, gelatin, cellulose derivatives or polyacrylamide.
The further technical scheme is that in the step one, the mass ratio of the comonomer, the acrylonitrile, the pore-forming agent and the oily initiator in the oil phase is 100: (0.1-150): (20-300): (0.01 to 3); the mass ratio of water to the dispersing agent in the water phase is 100: (0.005-5); the mass ratio of the water phase to the oil phase is 100: (10-90); the reaction temperature of the suspension polymerization is 40-90 ℃, and the polymerization time is 2-10 hours.
In the second step, the inorganic acid is at least one of hydrochloric acid, sulfuric acid, nitric acid, boric acid and phosphoric acid; the inorganic base is at least one of sodium hydroxide, ammonium hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate;
the mass ratio of water to inorganic acid in the acid solution is 100: (0.01-10); the mass ratio of water to inorganic alkali in the alkali liquor is 100: (0.01-10). The temperature of the acid treatment is 5-90 ℃, and the treatment time is 0.1-48 hours; the acid treatment adopts a stirring or soaking mode; the temperature of the alkali treatment is 5-90 ℃, and the treatment time is 0.1-48 hours; the alkali treatment adopts a stirring or soaking mode.
In addition, the cross-linked acrylonitrile-based copolymer microsphere adsorbent can have a specific pore structure by adjusting the structure of the chemical groups of the framework of the adsorbent (such as introduction of groups with charges) and the type and content of pore-forming agents, and can ensure the adsorption and removal performance of endogenous or exogenous toxicants or pathogenic substances in blood, such as rogor, pentobarbital sodium, interleukin 6(IL-6), hormone parathyroid hormone, indoxyl sulfate, bilirubin sulfate, bile acid toxin and the like in the immune field, such as adsorption of rogor parathyroid hormone, indoxyl sulfate, bile acid-cresol, bile acid.
The adsorbent for whole blood perfusion is obtained by copolymerization and crosslinking of a comonomer and an acrylonitrile monomer and certain acid and alkali treatment. Wherein, acrylonitrile chain segment component is introduced into the traditional cross-linked polymer microsphere material to improve the mechanical strength of the resin microsphere; the introduction of acrylonitrile in the adsorbent improves the hydrophilicity of the adsorbent material; in addition, during the acid treatment and alkali treatment processes of the preparation of the adsorbent, the cyano group of the acrylonitrile component in the adsorbent can be partially hydrolyzed to form carboxylic acid, amido, imido and other groups, so that the hydrophilicity of the adsorbent material can be further improved, and the blood compatibility of the material can be further improved; the cross-linked acrylonitrile-based copolymer microsphere adsorbent has a special porous cross-linked structure and chemical groups, and can ensure the adsorption performance on different toxins while providing mechanical strength and hydrophilicity.
Compared with the prior art, the invention has the following advantages and beneficial effects:
1. the adsorbent prepared by the invention has high mechanical strength, reduces particle damage and improves the use safety of the adsorbent resin.
2. The adsorbent prepared by the invention has good hydrophilicity and high blood compatibility, and can be suitable for whole blood perfusion;
3. the adsorbent prepared by the invention has excellent adsorption and removal performance on endogenous or exogenous toxicants or pathogenic substances in blood.
Detailed Description
The following describes in detail specific embodiments of the present invention with reference to examples, but the embodiments of the present invention are not limited thereto.
Example 1
(1) Suspension polymerization is carried out by uniformly stirring 60g of vinylpyridine, 20g of styrene, 20g of divinylbenzene, 100g of acrylonitrile, 100g of toluene and 2g of benzoyl peroxide to form an oil phase; mixing 400g of water and 3g of hydroxypropyl methyl cellulose, and uniformly stirring to obtain a water phase; adding the oil phase into the water phase, stirring and suspending at 80 ℃ for 8 hours, and removing the pore-foaming agent in the resin obtained by polymerization to obtain polymeric microspheres;
(2) acid-base treatment
Mixing water and hydrochloric acid, and stirring uniformly to prepare acid solution with the hydrochloric acid concentration of 5 wt%; mixing water and sodium hydroxide, and stirring uniformly to prepare an alkali liquor with the sodium hydroxide concentration of 5 wt%; placing the polymeric microspheres obtained in the step (1) in acid liquor, and stirring and carrying out acid treatment for 8 hours at the temperature of 80 ℃; then, placing the polymeric microspheres in alkali liquor, and stirring and carrying out alkali treatment for 8 hours at the temperature of 80 ℃; and purifying to obtain the high-mechanical-strength hydrophilic adsorbent for whole blood perfusion.
Comparative example 1-1
The adsorbent of this comparative example was not subjected to acid-base treatment.
60g of vinylpyridine, 20g of styrene, 20g of divinylbenzene, 100g of acrylonitrile, 100g of toluene and 2g of benzoyl peroxide are uniformly stirred to form an oil phase; mixing 400g of water and 3g of hydroxypropyl methyl cellulose, and uniformly stirring to obtain a water phase; adding the oil phase into the water phase, stirring and suspending at 80 ℃ for 8 hours, and removing the pore-forming agent in the resin obtained by polymerization to obtain the polymeric microspheres as a control example.
Comparative examples 1 to 2
The adsorbent in this comparative example was acrylonitrile-free.
(1) Suspension polymerization is carried out by uniformly stirring 60g of vinylpyridine, 20g of styrene, 20g of divinylbenzene, 50g of toluene and 1g of benzoyl peroxide to form an oil phase; mixing 200g of water and 1.5g of hydroxypropyl methyl cellulose, and uniformly stirring to obtain a water phase; adding the oil phase into the water phase, stirring and suspending at 80 ℃ for 8 hours, and removing the pore-foaming agent in the resin obtained by polymerization to obtain polymeric microspheres;
(2) acid-base treatment
Mixing water and hydrochloric acid, and stirring uniformly to prepare acid solution with the hydrochloric acid concentration of 5 wt%; mixing water and sodium hydroxide, and stirring uniformly to prepare an alkali liquor with the sodium hydroxide concentration of 5 wt%; placing the polymeric microspheres obtained in the step (1) in acid liquor, and stirring and carrying out acid treatment for 8 hours at the temperature of 80 ℃; then, placing the polymeric microspheres in alkali liquor, and stirring and carrying out alkali treatment for 8 hours at the temperature of 80 ℃; and purifying to obtain the high-mechanical-strength hydrophilic adsorbent for whole blood perfusion.
Example 2
(1) Suspension polymerization is carried out by uniformly stirring 50g of styrene, 5g of vinylpyridine, 5g of methacryloyloxyethyl trimethyl ammonium chloride, 20g of methyl styrene, 20g of divinylbenzene, 50g of acrylonitrile, 150g of toluene and 2g of azobisisobutyronitrile to form an oil phase; mixing 350g of water and 2g of hydroxyethyl cellulose, and uniformly stirring to obtain a water phase; adding the oil phase into the water phase, stirring and suspending at 70 ℃ for 10 hours, and removing the pore-foaming agent in the resin obtained by polymerization to obtain polymeric microspheres;
(2) acid-base treatment
Mixing water and hydrochloric acid, and stirring uniformly to prepare acid solution with the hydrochloric acid concentration of 2 wt%; mixing water and sodium hydroxide, and stirring uniformly to prepare an alkali liquor with the sodium hydroxide concentration of 1 wt%; placing the polymeric microspheres obtained in the step (1) in acid liquor, and stirring and carrying out acid treatment for 24 hours at the temperature of 30 ℃; then, putting the polymeric microspheres into alkali liquor, and stirring and carrying out alkali treatment for 12 hours at the temperature of 40 ℃; and purifying to obtain the high-mechanical-strength hydrophilic adsorbent for whole blood perfusion.
Control 2-1
The adsorbent of this comparative example was not subjected to acid-base treatment.
Uniformly stirring 50g of styrene, 5g of vinylpyridine, 5g of methacryloyloxyethyl trimethyl ammonium chloride, 20g of methyl styrene, 20g of divinylbenzene, 50g of acrylonitrile, 150g of toluene and 2g of azobisisobutyronitrile to form an oil phase; mixing 350g of water and 2g of hydroxyethyl cellulose, and uniformly stirring to obtain a water phase; adding the oil phase into the water phase, stirring and suspending for 10 hours at 70 ℃, removing the pore-forming agent in the resin obtained by polymerization, and obtaining the polymeric microspheres as a comparison example.
Comparative example 2-2
The adsorbent in this comparative example was acrylonitrile-free.
(1) Suspension polymerization is carried out by uniformly stirring 50g of styrene, 5g of vinylpyridine, 5g of methacryloyloxyethyl trimethyl ammonium chloride, 20g of methyl styrene, 20g of divinylbenzene, 150g of toluene and 1.3g of azobisisobutyronitrile to form an oil phase; mixing 350g of water and 2g of hydroxyethyl cellulose, and uniformly stirring to obtain a water phase; adding the oil phase into the water phase, stirring and suspending at 70 ℃ for 10 hours, and removing the pore-foaming agent in the resin obtained by polymerization to obtain polymeric microspheres;
(2) acid-base treatment
Mixing water and hydrochloric acid, and stirring uniformly to prepare acid solution with the hydrochloric acid concentration of 2 wt%; mixing water and sodium hydroxide, and stirring uniformly to prepare an alkali liquor with the sodium hydroxide concentration of 1 wt%; placing the polymeric microspheres obtained in the step (1) in acid liquor, and stirring and carrying out acid treatment for 24 hours at the temperature of 30 ℃; then, putting the polymeric microspheres into alkali liquor, and stirring and carrying out alkali treatment for 12 hours at the temperature of 40 ℃; and purifying to obtain the high-mechanical-strength hydrophilic adsorbent for whole blood perfusion.
Example 3
(1) Suspension polymerization is carried out by uniformly stirring 20g of styrene, 80g of ethyl styrene, 20g of divinylbenzene, 80g of acrylonitrile, 100g of toluene, 100g of methylcyclohexane and 0.5g of benzoyl peroxide to form an oil phase; mixing 500g of water and 10g of gelatin, and uniformly stirring to obtain a water phase; adding the oil phase into the water phase, stirring and suspending at 78 ℃ for 5 hours, and removing the pore-foaming agent in the resin obtained by polymerization to obtain polymeric microspheres;
(2) acid-base treatment
Mixing water and phosphoric acid, and stirring uniformly to prepare acid liquor with the phosphoric acid concentration of 10 wt%; mixing water and potassium hydroxide, and stirring uniformly to prepare an alkali liquor with the potassium hydroxide concentration of 2 wt%; placing the polymeric microspheres obtained in the step (1) in acid liquor, and stirring and carrying out acid treatment for 10 hours at the temperature of 40 ℃; then, placing the polymeric microspheres in alkali liquor, and stirring and carrying out alkali treatment for 12 hours at the temperature of 50 ℃; and purifying to obtain the high-mechanical-strength hydrophilic adsorbent for whole blood perfusion.
Control 3
The adsorbent of this comparative example was not subjected to acid-base treatment.
20g of styrene, 80g of ethyl styrene, 20g of divinylbenzene, 80g of acrylonitrile, 100g of toluene, 100g of methylcyclohexane and 0.5g of benzoyl peroxide are uniformly stirred to form an oil phase; mixing 500g of water and 10g of gelatin, and uniformly stirring to obtain a water phase; adding the oil phase into the water phase, stirring and suspending at 78 ℃ for 5 hours, and removing the pore-forming agent in the resin obtained by polymerization to obtain the polymeric microspheres as a control example.
Example 4
(1) Suspension polymerization is carried out by uniformly stirring 40g of styrene, 10g of methyl methacrylate, 50g of divinylbenzene, 150g of acrylonitrile, 20g of xylene and 0.01g of azobisisobutyronitrile to form an oil phase; mixing 2700g of water and 0.135g of polyvinyl alcohol, and uniformly stirring to obtain a water phase; adding the oil phase into the water phase, stirring and suspending at 80 ℃ for 2 hours, and removing the pore-foaming agent in the resin obtained by polymerization to obtain polymeric microspheres;
(2) acid-base treatment
Mixing water and nitric acid, and stirring uniformly to prepare acid liquor with the nitric acid concentration of 0.01 wt%; mixing water and sodium hydroxide, and stirring uniformly to prepare an alkali liquor with the sodium hydroxide concentration of 1 wt%; placing the polymeric microspheres obtained in the step (1) in acid liquor, and stirring and carrying out acid treatment for 48 hours at the temperature of 5 ℃; then, putting the polymeric microspheres into alkali liquor, and stirring and carrying out alkali treatment for 0.1 hour at the temperature of 90 ℃; and purifying to obtain the high-mechanical-strength hydrophilic adsorbent for whole blood perfusion.
Control 4
The adsorbent of this comparative example was not subjected to acid-base treatment.
Uniformly stirring 40g of styrene, 10g of methyl methacrylate, 50g of divinylbenzene, 150g of acrylonitrile, 20g of xylene and 0.01g of azobisisobutyronitrile to form an oil phase; mixing 2700g of water and 0.135g of polyvinyl alcohol, and uniformly stirring to obtain a water phase; adding the oil phase into the water phase, stirring and suspending for 2 hours at the temperature of 80 ℃, and removing the pore-forming agent in the resin obtained by polymerization to obtain the polymeric microspheres as a comparison example.
Example 5
(1) Suspension polymerization is carried out by uniformly stirring 30g of isooctyl acrylate, 70g of divinylbenzene, 0.1g of acrylonitrile, 300g of ethyl acetate and 3g of benzoyl peroxide to form an oil phase; mixing 800g of water and 40g of hydroxyethyl cellulose, and uniformly stirring to obtain a water phase; adding the oil phase into the water phase, stirring and suspending at 40 ℃ for 10 hours, and removing the pore-foaming agent in the resin obtained by polymerization to obtain polymeric microspheres;
(2) acid-base treatment
Mixing water and sulfuric acid, and stirring uniformly to prepare acid liquor with the sulfuric acid concentration of 2 wt%; mixing water and ammonium hydroxide, and stirring to obtain 0.01 wt% ammonium hydroxide solution; placing the polymeric microspheres obtained in the step (1) in acid liquor, and stirring and carrying out acid treatment for 0.1 hour at the temperature of 90 ℃; then, placing the polymeric microspheres in alkali liquor, and stirring for alkali treatment for 48 hours at the temperature of 5 ℃; and purifying to obtain the high-mechanical-strength hydrophilic adsorbent for whole blood perfusion.
Control 5
The adsorbent of this comparative example was not subjected to acid-base treatment.
An oil phase is formed by uniformly stirring 30g of isooctyl acrylate, 70g of divinylbenzene, 0.1g of acrylonitrile, 300g of ethyl acetate and 3g of benzoyl peroxide; mixing 800g of water and 40g of hydroxyethyl cellulose, and uniformly stirring to obtain a water phase; adding the oil phase into the water phase, stirring and suspending for 10 hours at 40 ℃, removing the pore-forming agent in the resin obtained by polymerization, and obtaining the polymeric microspheres as a comparison example.
For the adsorbents obtained in each of the above examples and the corresponding control example, while taking a commercial resin AMBERLITE XAD16 as a reference, mechanical strength, evaluation of hemolysis and platelet adhesion, evaluation of pore size distribution and adsorption performance were sequentially carried out.
(1) Evaluation of mechanical Strength of adsorbent
The compressive strength of the particles and the sphericity ratio after grinding of the resin were respectively measured by a particle strength tester and a ball mill, and the mechanical strength of the adsorbent was comprehensively evaluated, with the results as shown in table 1 below:
TABLE 1 resin Strength test results of examples and comparative examples
Figure RE-GDA0002434048840000081
As can be seen from Table 1, the adsorbents of examples 1 to 5 of the present invention have significantly higher particle strength and sphericity after grinding, compared to the adsorbents containing no acrylonitrile such as comparative examples 1 to 2, comparative examples 2 to 2, and XAD 16. The invention can effectively improve the mechanical strength of the macromolecular crosslinking porous resin by introducing acrylonitrile into the system.
(2) Hemolysis and platelet adhesion were evaluated as follows:
hemolysis and platelet adhesion assays were tested according to GB/T16886.4-2003 and GB/T16175-1996. See table 2 below for results.
Table 2: evaluation data of hemolysis and platelet adhesion in examples and comparative examples
Figure RE-GDA0002434048840000091
As can be seen from the results in table 2, examples 1 to 5 have lower hemolysis rate and platelet adhesion rate, showing better hemocompatibility; and the hemolysis rate and the platelet adhesion rate were significantly reduced as compared with control examples 1-2, 2-2 and XAD 16. The introduction of hydrophilic groups into the system can improve the blood compatibility of the material. Among them, from the comparison between example 1 and comparative example 1-1, and between example 2 and comparative example 2-1, it can be found that example 1 and example 2, which were subjected to acid-base treatment, have lower hemolysis rate and platelet adhesion rate, showing better blood compatibility. Meanwhile, the adsorbents of examples 1 to 5 of the present invention all showed excellent biocompatibility results when tested for biocompatibility such as cytotoxicity, thrombosis, coagulation, complement activation, immunity, etc.
(3) Pore size distribution
The specific surface area and pore analyzer and the N2 adsorption-desorption method are adopted to determine the pore diameter and specific surface area data of the resin.
TABLE 3 evaluation data of pore structures of examples and comparative examples
Figure RE-GDA0002434048840000101
From the comparison of the examples with the comparative examples, it is understood that adsorbents having different pore structures can be obtained by changing the preparation process conditions. The increase of the average pore diameter of the adsorbent is beneficial to improving the adsorption performance.
(4) The operating method for the adsorption performance evaluation is as follows:
10ml of plasma solutions containing Dimethoate, sodium pentobarbital, interleukin 6(IL-6), TNF- α, PTH, bilirubin, bile acid, PCS, and IS were added to 1ml of the adsorption resins obtained in the above examples and comparative examples, and after shaking at 37 ℃ for 2 hours, changes in the adsorbed substances were measured, respectively, and the results are shown in tables 4 and 5 below.
Table 4: adsorption Performance data of examples and comparative examples
Figure RE-GDA0002434048840000111
As can be seen from the results in Table 4, the adsorbents prepared in examples 1 to 5 have higher adsorption rates to parathyroid hormone (PTH), dimethoate, sodium pentobarbital, interleukin IL-6 and tumor necrosis factor TNF-a, which are better than the adsorption rates of the control samples; compared with comparative examples 1-2, 2-2 and XAD16, the adsorbents prepared by introducing acrylonitrile into the system (examples 1-5, 1-1 and 2-1) show a significantly lower protein adsorption rate and better blood compatibility; from comparison between example 1 and comparative example 1-1, and between example 2 and comparative example 2-1, it can be seen that example 1 and example 2 which were subjected to acid-base treatment have lower protein adsorption rates, showing better blood compatibility.
Table 5: adsorption Performance data for protein-bound toxins of examples and comparative examples
Figure RE-GDA0002434048840000121
As can be seen from the results in table 5, the adsorbents prepared in examples 1 to 5 have better adsorption performance for protein-bound toxoids such as total bilirubin, total bile acid, Indoxyl Sulfate (IS), and p-cresol sulfate (PCS).
Finally, it should be emphasized that the above-described preferred embodiments of the present invention are merely examples of implementations, not limitations, and various changes and modifications may be made by those skilled in the art, without departing from the spirit and scope of the invention, and any changes, equivalents, improvements, etc. made within the spirit and scope of the present invention are intended to be embraced therein.

Claims (5)

1. The adsorbent for the high-mechanical-strength hydrophilic whole blood perfusion is a cross-linked acrylonitrile-based copolymer microsphere, and the cross-linked acrylonitrile-based copolymer microsphere has a porous cross-linked structure; the particle size of the adsorbent is in the range of 0.05mm to 3 mm.
2. A preparation method of an adsorbent for high-mechanical-strength hydrophilic whole blood perfusion is characterized by comprising the following steps:
the method comprises the following steps: suspension polymerization
An oil phase is composed of a comonomer, acrylonitrile, a pore-forming agent and an oily initiator, the oil phase is subjected to suspension polymerization in a water phase composed of a dispersant and water, and the pore-forming agent in the polymerized resin is removed to obtain polymeric microspheres;
step two: acid-base treatment
And (3) placing the polymeric microspheres obtained in the step one in an acid solution consisting of inorganic acid and water for acid treatment, then placing in an alkali solution consisting of inorganic base and water for alkali treatment, and purifying to obtain the high-mechanical-strength hydrophilic adsorbent for whole blood perfusion.
3. The method for preparing the adsorbent for high mechanical strength hydrophilic whole blood perfusion according to claim 2, wherein the adsorbent comprises:
in step one, the comonomer is vinylpyridine, methacryloyloxyethyltrimethylammonium chloride, styrene, methylstyrene, ethylstyrene, divinylbenzene, methyl acrylate, methyl methacrylate, ethyl acrylate, ethyl methacrylate, butyl acrylate, butyl methacrylate, isooctyl acrylate, acrylamide, isobutyl acrylate, lauryl methacrylate, isooctyl acrylate, tert-butyl acrylate, polyethylene glycol diacrylate, polyethylene glycol dimethacrylate, isobornyl acrylate, 1, 6-hexanediol diacrylate, glycerol trimethylolpropane triacrylate, polydipentaerythritol hexaacrylate, dipropylene glycol diacrylate, polyethylene glycol o-phenylphenyl ether acrylate, tripropylene glycol diacrylate, trimethylolpropane trimethacrylate, poly (t-butyl acrylate), at least one of triethoxy trimethylolpropane triacrylate, tris (2-hydroxyethyl) isocyanurate triacrylate and 2-phenoxyethyl acrylate; the pore-foaming agent is at least one of toluene, xylene, ethyl acetate, butyl acetate, cyclohexane or methylcyclohexane; the oily initiator is at least one of benzoyl peroxide or azobisisobutyronitrile; the dispersing agent is at least one of polyvinyl alcohol, gelatin, cellulose derivatives or polyacrylamide.
4. The method for preparing the adsorbent for high mechanical strength hydrophilic whole blood perfusion according to claim 2, wherein the adsorbent comprises:
in the first step, the mass ratio of the comonomer, the acrylonitrile, the pore-forming agent and the oily initiator in the oil phase is 100: (0.1-150): (20-300): (0.01 to 3); the mass ratio of water to the dispersing agent in the water phase is 100: (0.005-5); the mass ratio of the water phase to the oil phase is 100: (10-90); the reaction temperature of the suspension polymerization is 40-90 ℃, and the polymerization time is 2-10 hours.
5. The method for preparing the adsorbent for high mechanical strength hydrophilic whole blood perfusion according to claim 2, wherein the adsorbent comprises:
in the second step, the inorganic acid is at least one of hydrochloric acid, sulfuric acid, nitric acid, boric acid and phosphoric acid; the inorganic base is at least one of sodium hydroxide, ammonium hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate;
the mass ratio of water to inorganic acid in the acid solution is 100: (0.01-10); the mass ratio of water to inorganic alkali in the alkali liquor is 100: (0.01-10); the temperature of the acid treatment is 5-90 ℃, and the treatment time is 0.1-48 hours; the temperature of the alkali treatment is 5-90 ℃, and the treatment time is 0.1-48 hours.
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CN112791712A (en) * 2021-01-05 2021-05-14 南开大学 Adsorbent for removing protein-bound uremic toxin through blood perfusion and preparation method thereof
CN113262762A (en) * 2021-05-06 2021-08-17 西安蓝深环保科技有限公司 Adsorbing material for blood perfusion and preparation method thereof
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