CN115896086B - Radiation-resistant filler for blood perfusion device and preparation method thereof - Google Patents
Radiation-resistant filler for blood perfusion device and preparation method thereof Download PDFInfo
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- Immobilizing And Processing Of Enzymes And Microorganisms (AREA)
Abstract
The invention discloses an irradiation-resistant filler for a blood perfusion device and a preparation method thereof, comprising the following steps: (1) preparation of melamine zinc salicylate hydrogel; (2) preparation of hydrogel particles; (3) immobilized enzyme network carrier particles; and (4) preparing the radiation-resistant filler. The zinc-containing reticular structure particles prepared by the method are used for immobilizing the urate oxidase, and the rich zinc-containing loose reticular structure wraps the urate oxidase therein, so that a certain amount of radiation can be well absorbed; simultaneously, the natural radiation-resistant functional enzyme is immobilized on the filler of the blood perfusion device, and the functional enzyme can rapidly remove free radicals generated in the radiation sterilization process, so that the influence of radiation sterilization on the activity of urate oxidase on the filler of the blood perfusion device is reduced.
Description
Technical Field
The invention belongs to the technical field of hemoperfusion adsorption resins, and particularly relates to an irradiation-resistant filler for a hemoperfusion apparatus and a preparation method thereof.
Background
The blood perfusion is a blood purification technology for introducing the blood of a patient into a perfusion device filled with a solid adsorbent, and removing exogenous or endogenous toxins, medicines or metabolic wastes which cannot be removed by dialysis in the blood of the patient through the adsorption effect of an adsorbent filler, and is mainly used for rescuing medicines and poisoning, and can also be used for removing macromolecular toxins in the body of a patient subjected to chronic renal failure maintenance dialysis together with hemodialysis.
Among them, the solid adsorbent filler used in the blood perfusion device is mostly made of polystyrene resin or activated carbon, and has been innovated in recent years, and there are cases where the blood perfusion device using immunoadsorbent or immobilized enzyme as the filler is marketed. The blood perfusion device using the directional adsorption or the directional decomposition of harmful substances in blood as a treatment means has definite target points, good clinical effect and urgent needs of patients. However, the main sterilization method of the blood perfusion device is radiation sterilization, and the effect of the immunoadsorbent or immobilized enzyme is greatly reduced after the radiation sterilization, so that the new blood perfusion device of the type is slowly developed.
The irradiation sterilization achieves the sterilization effect through the combination of direct action and indirect action, and the direct action of irradiation rays mainly comprises the step that photon energy is stored on a target structure to cause external electrons of molecules to shift from the molecules so as to break covalent bonds. The indirect effect is mainly that rays act on water molecules, oxygen molecules or other molecules to form high-activity free radicals and active oxygen, so that nucleic acid or protein chains are broken. A number of documents demonstrate that indirect effects are reduced when proteins are frozen to ultra low temperatures, as are removal of water and oxygen or addition of radical scavengers, but that free radical scavengers for irradiation sterilization are currently lacking.
The Chinese patent application No. 201711186695.7 discloses a preparation method of immobilized enzyme, which comprises the following steps: (1) Dissolving enzyme in buffer solution to prepare enzyme solution, mixing with adsorption material, oscillating for adsorption for a certain time, filtering to obtain adsorption immobilized enzyme; (2) Dissolving a film-covered protective agent in a buffer solution to prepare a protective agent solution, placing the adsorption immobilized enzyme in the protective agent solution, oscillating for a certain time, filtering out and draining to obtain the adsorption immobilized enzyme treated by the protective agent; (3) Dissolving a coating material in a solvent to prepare a coating solution, mixing the adsorption immobilized enzyme treated by a protective agent with the coating solution, oscillating the coating for a certain time, filtering out and drying; (4) Finally, washing with deionized water or buffer solution to obtain the adsorption-coating film combined immobilized enzyme. The method has the advantages of mild conditions in the adsorption and film coating processes, high recovery rate of enzyme activity, high stability of immobilized enzyme, simple operation and low cost. However, the immobilized enzyme prepared by the method cannot guarantee the great reduction of the enzyme activity on the filler during irradiation sterilization.
At present, researchers have made sterilization protection to immunoadsorbent or immobilized enzyme to different degrees, but most of them mainly use radiation protection agents, the effect is poor, and the radiation protection agents are easy to enter human bodies in actual clinical application, so that a series of immunogenicity and cytotoxicity problems are generated.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide an irradiation-resistant filler for a hemoperfusion apparatus and a preparation method thereof, and zinc-containing netlike structure particles prepared by the invention are used for immobilizing urate oxidase, and abundant zinc-containing loose netlike structures wrap the urate oxidase therein, so that a certain amount of irradiation can be well absorbed; simultaneously, the natural radiation-resistant functional enzyme is immobilized on the filler of the blood perfusion device, and the functional enzyme can rapidly remove free radicals generated in the radiation sterilization process, so that the influence of radiation sterilization on the activity of urate oxidase on the filler of the blood perfusion device is reduced.
In order to achieve the above purpose, the present invention provides the following technical solutions:
a method for preparing radiation-resistant filler for a hemoperfusion apparatus, comprising the steps of:
(1) Preparation of zinc melamine salicylate hydrogel: adding deionized water into a beaker, then adding zinc sulfate, melamine and salicylic acid, fully and uniformly mixing, carrying out constant-temperature oscillation reaction, and cooling to room temperature after the reaction is completed to obtain melamine zinc salicylate hydrogel;
(2) Preparation of hydrogel particles: adding n-hexane and sorbitan trioleate (Span 85) into a beaker, then adding the melamine zinc salicylate hydrogel obtained in the step (1), and carrying out stirring reaction to obtain a hydrogel particle mixed solution after the reaction is completed;
(3) Immobilized enzyme network carrier particles: adding 2-methylimidazole into the hydrogel particle mixed solution obtained in the step (2), oscillating at constant temperature, cooling to room temperature after the oscillating is completed, and performing filtration, washing and drying treatment to obtain a particle product; then adding the granular product into deionized water, soaking at constant temperature, and then filtering and drying to obtain immobilized enzyme reticular carrier particles;
(4) Preparation of radiation-resistant filler: adding the immobilized enzyme reticular carrier particles obtained in the step (3) into Tris buffer solution, then adding urate oxidase and functional enzyme for constant-temperature oscillation, and then filtering and drying to obtain the radiation-resistant filler.
Preferably, in the step (1), the mass ratio of zinc sulfate, melamine, salicylic acid and deionized water is 10-20:70-90:20-40:800-1000.
Preferably, the reaction temperature of the constant temperature oscillation reaction in the step (1) is 65-90 ℃ and the reaction time is 2-4h.
Preferably, the mass ratio of the n-hexane, sorbitan trioleate and zinc melamine salicylate hydrogel in the step (2) is 130-200:3-8:900-1140.
Preferably, in the step (2), the stirring reaction temperature is 50-70 ℃, the reaction time is 2-4h, and the stirring speed is 150-250r/min.
Preferably, in the step (3), the mass ratio of the 2-methylimidazole to the hydrogel particle mixed solution is 4-8:1000-1400.
Preferably, in the step (3), the constant temperature oscillation temperature is 60-70 ℃ and the oscillation time is 1-2h; the constant-temperature soaking temperature is 70-90 ℃ and the soaking time is 12-18h.
Preferably, the pH of the Tris buffer in step (4) is 8.0-9.0; the functional enzyme is one or more of superoxide dismutase (SOD) and catalase; the mass ratio of the immobilized enzyme reticular carrier particles to the Tris buffer solution to the urate oxidase to the functional enzyme is 50:100-150:0.01-0.03:0.01-0.02.
Preferably, the constant temperature oscillation temperature in the step (4) is 30-40 ℃ and the oscillation time is 2-4h.
The invention also provides the radiation-resistant filler for the blood perfusion device, which is prepared by the method.
Compared with the prior art, the invention has the following beneficial effects:
(1) According to the preparation method of the radiation-resistant filler for the blood perfusion device, the hydrogel is prepared by zinc sulfate, melamine and salicylic acid, then hydrogel particles are obtained by stirring under the conditions of an emulsifier sorbitan trioleate and a solvent n-hexane, then 2-methylimidazole is added to solidify the hydrogel, residual hydrogel is removed, zinc-containing network structure particles are obtained to immobilize urate oxidase, and the urate oxidase is wrapped in the zinc-containing network structure, so that a certain amount of radiation can be well absorbed; and simultaneously, the natural radiation-resistant functional enzyme is immobilized on the filler of the blood perfusion device, so that the functional enzyme can rapidly remove free radicals generated in the radiation sterilization process, and the influence of radiation sterilization on the activity of urate oxidase on the filler of the blood perfusion device is reduced.
(2) Compared with the traditional disposable filling material of the blood perfusion device, the irradiation-resistant filling material for the blood perfusion device can realize industrialization of more immobilized enzymes or immobilized proteins which are not resistant to irradiation originally, expand the indication range of the traditional blood perfusion device and enrich the clinical treatment means.
(3) The radiation-resistant filler for the blood perfusion device has the advantages of dense filler network structure, quicker substrate and product exchange, more efficient reaction with single substances in blood, shortened treatment time of whole blood perfusion, reduced possibility of treatment risk, improved medical resource utilization rate and greater economic and social benefits.
Detailed Description
The technical solutions of the present invention will be clearly and completely described in conjunction with the embodiments of the present invention, and it is apparent that the described embodiments are only some embodiments of the present invention, but not all embodiments. 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 method for preparing radiation-resistant filler for a hemoperfusion apparatus, comprising the steps of:
(1) Preparation of zinc melamine salicylate hydrogel: adding 800g of deionized water into a beaker, then adding 10g of zinc sulfate, 70g of melamine and 20g of salicylic acid, fully and uniformly mixing, placing the beaker into a water bath kettle at 65 ℃, carrying out constant-temperature oscillating reaction for 4 hours, and cooling to room temperature after the reaction is completed to obtain melamine zinc salicylate hydrogel;
(2) Preparation of hydrogel particles: adding 200mL of n-hexane and 3g of sorbitan trioleate into a beaker, then pouring the melamine zinc salicylate hydrogel (900 g) obtained in the step (1) into the beaker, placing the beaker into a water bath kettle at 50 ℃, and reacting for 4 hours at a stirring speed of 150r/min, thus obtaining a hydrogel particle mixed solution after the reaction is completed;
(3) Immobilized enzyme network carrier particles: adding 4g of 2-methylimidazole into the hydrogel particle mixed solution (1100 g) obtained in the step (2), oscillating for 2 hours at a constant temperature of 60 ℃, cooling to room temperature after oscillating, filtering out a product, washing 3 times, and drying in a drying oven at 75 ℃ for 5 hours to obtain a particle product; then adding the granular product into 1L of deionized water, soaking for 18 hours at a constant temperature of 70 ℃, and then filtering and drying to obtain immobilized enzyme reticular carrier particles;
(4) Preparation of radiation-resistant filler: adding 50g of immobilized enzyme reticular carrier particles (obtained in the step (3) into 100g of Tris buffer solution with pH of 8.0, then adding 10mg of urate oxidase, 5mg of superoxide dismutase and 5mg of catalase, oscillating for 4 hours at a constant temperature of 30 ℃, filtering, and drying in vacuum to obtain the radiation-resistant filler.
Example 2
A method for preparing radiation-resistant filler for a hemoperfusion apparatus, comprising the steps of:
(1) Preparation of zinc melamine salicylate hydrogel: adding 900g of deionized water into a beaker, then adding 13g of zinc sulfate, 80g of melamine and 30g of salicylic acid, fully and uniformly mixing, placing the beaker into a water bath kettle at 75 ℃, carrying out constant-temperature oscillating reaction for 3 hours, and cooling to room temperature after the reaction is completed to obtain melamine zinc salicylate hydrogel;
(2) Preparation of hydrogel particles: adding 250mL of n-hexane and 5g of sorbitan trioleate into a beaker, pouring the melamine zinc salicylate hydrogel (1020 g) obtained in the step (1) into the beaker, placing the beaker into a water bath kettle at 60 ℃, and reacting for 3 hours at a stirring speed of 200r/min, thus obtaining a hydrogel particle mixed solution after the reaction is completed;
(3) Immobilized enzyme network carrier particles: adding 5g of 2-methylimidazole into the hydrogel particle mixed solution (1200 g) obtained in the step (2), oscillating for 2 hours at a constant temperature of 65 ℃, cooling to room temperature after oscillating, filtering out a product, washing 3 times, and drying in a drying oven at 75 ℃ for 5 hours to obtain a particle product; then adding the granular product into 1L of deionized water, soaking for 16 hours at the constant temperature of 80 ℃, and then filtering and drying to obtain immobilized enzyme reticular carrier particles;
(4) Preparation of radiation-resistant filler: adding the immobilized enzyme reticular carrier particles (50 g) obtained in the step (3) into 120g of Tris buffer solution with pH of 8.5, then adding 20mg of urate oxidase and 10mg of superoxide dismutase, oscillating for 3 hours at a constant temperature of 35 ℃, then filtering, and drying in vacuum to obtain the radiation-resistant filler.
Example 3
A method for preparing radiation-resistant filler for a hemoperfusion apparatus, comprising the steps of:
(1) Preparation of zinc melamine salicylate hydrogel: adding 900g of deionized water into a beaker, then adding 17g of zinc sulfate, 85g of melamine and 35g of salicylic acid, fully and uniformly mixing, placing the beaker into a water bath kettle at 80 ℃, carrying out constant-temperature oscillating reaction for 3 hours, and cooling to room temperature after the reaction is completed to obtain melamine zinc salicylate hydrogel;
(2) Preparation of hydrogel particles: adding 250mL of n-hexane and 6g of sorbitan trioleate into a beaker, then pouring the melamine zinc salicylate hydrogel (1020 g) obtained in the step (1) into the beaker, placing the beaker into a water bath kettle at 60 ℃, and reacting for 3 hours at a stirring speed of 200r/min, thus obtaining a hydrogel particle mixed solution after the reaction is completed;
(3) Immobilized enzyme network carrier particles: adding 7g of 2-methylimidazole into the hydrogel particle mixed solution (1200 g) obtained in the step (2), oscillating for 1h at a constant temperature of 65 ℃, cooling to room temperature after oscillating, filtering out a product, washing 3 times, and drying in an oven at 80 ℃ for 4h to obtain a particle product; then adding the granular product into 1L of deionized water, soaking for 14 hours at the constant temperature of 80 ℃, and then filtering and drying to obtain immobilized enzyme reticular carrier particles;
(4) Preparation of radiation-resistant filler: adding the immobilized enzyme reticular carrier particles (50 g) obtained in the step (3) into 130g of Tris buffer solution with pH of 9.0, then adding 25mg of urate oxidase and 10mg of catalase, oscillating for 3 hours at a constant temperature of 35 ℃, then filtering, and drying in vacuum to obtain the radiation-resistant filler.
Example 4
A method for preparing radiation-resistant filler for a hemoperfusion apparatus, comprising the steps of:
(1) Preparation of zinc melamine salicylate hydrogel: adding 1000g of deionized water into a beaker, then adding 20g of zinc sulfate, 90g of melamine and 40g of salicylic acid, fully and uniformly mixing, placing the beaker into a water bath kettle at 90 ℃, carrying out constant-temperature oscillating reaction for 2 hours, and cooling to room temperature after the reaction is completed to obtain melamine zinc salicylate hydrogel;
(2) Preparation of hydrogel particles: adding 300mL of normal hexane and 8g of sorbitan trioleate into a beaker, pouring 1140g of the zinc melamine salicylate hydrogel obtained in the step (1) into the beaker, placing the beaker into a water bath kettle at 70 ℃, and reacting for 2 hours at the stirring speed of 250r/min, thus obtaining a hydrogel particle mixed solution after the reaction is completed;
(3) Immobilized enzyme network carrier particles: 8g of 2-methylimidazole is added into the hydrogel particle mixed solution (1400 g) obtained in the step (2), the mixture is oscillated at a constant temperature of 70 ℃ for 1h, the mixture is cooled to room temperature after oscillation is completed, the product is filtered out, washed 3 times with water, and then dried in an oven at 80 ℃ for 3h to obtain a particle product; then adding the granular product into 1L of deionized water, soaking for 12 hours at a constant temperature of 90 ℃, and then filtering and drying to obtain immobilized enzyme reticular carrier particles;
(4) Preparation of radiation-resistant filler: adding 50g of immobilized enzyme reticular carrier particles (obtained in the step (3) into 150g of Tris buffer with the pH of 9.0, then adding 30mg of urate oxidase, 10mg of superoxide dismutase and 10mg of catalase, oscillating for 2 hours at a constant temperature of 40 ℃, filtering, and drying in vacuum to obtain the radiation-resistant filler.
Comparative example 1
A method for preparing radiation-resistant filler for a hemoperfusion apparatus, comprising the steps of:
(1) Preparation of zinc melamine salicylate hydrogel: adding 800g of deionized water into a beaker, then adding 10g of zinc sulfate, 70g of melamine and 20g of salicylic acid, fully and uniformly mixing, placing the beaker into a water bath kettle at 65 ℃, carrying out constant-temperature oscillating reaction for 4 hours, and cooling to room temperature after the reaction is completed to obtain melamine zinc salicylate hydrogel;
(2) Preparation of hydrogel particles: adding 200mL of n-hexane and 3g of sorbitan trioleate into a beaker, then pouring the melamine zinc salicylate hydrogel (900 g) obtained in the step (1) into the beaker, placing the beaker into a water bath kettle at 50 ℃, and reacting for 4 hours at a stirring speed of 150r/min, thus obtaining a hydrogel particle mixed solution after the reaction is completed;
(3) Immobilized enzyme network carrier particles: adding 4g of 2-methylimidazole into the hydrogel particle mixed solution (1100 g) obtained in the step (2), oscillating for 2 hours at a constant temperature of 60 ℃, cooling to room temperature after oscillating, filtering out a product, washing 3 times, and drying in a drying oven at 75 ℃ for 5 hours to obtain a particle product; then adding the granular product into 1L of deionized water, soaking for 18 hours at a constant temperature of 70 ℃, and then filtering and drying to obtain immobilized enzyme reticular carrier particles;
(4) Preparation of radiation-resistant filler: the immobilized enzyme reticular carrier particles (50 g) obtained in the step (3) are added into 100g of Tris buffer solution with pH of 8.0, then 10mg of urate oxidase is added, the mixture is oscillated for 4 hours at a constant temperature of 30 ℃, and then the mixture is filtered and dried in vacuum to obtain the radiation-resistant filler.
Comparative example 2
A method for preparing radiation-resistant filler for a hemoperfusion apparatus, comprising the steps of:
polystyrene resin particles (50 g) were added to 100g of Tris buffer having pH of 8.0, followed by 10mg of urate oxidase, 5mg of superoxide dismutase, 5mg of catalase, and shaking at constant temperature of 30℃for 4 hours, followed by filtration and vacuum drying to obtain a radiation-resistant filler.
The radiation-resistant fillers prepared in examples 1 to 4 and comparative examples 1 to 2 were used as a filler column of a blood perfusion apparatus, and after the column was packed, 25kGy of electron beam irradiation was used for sterilization, and after the sterilization, a uric acid perfusion effect test was performed using a blood simulation solution (uric acid concentration 1 mmol/L), and the radiation-resistant effect of the filler was detected by the concentration of uric acid after the perfusion.
Hemolysis experiment: sterilizing the radiation-resistant fillers obtained in examples 1-4 and comparative examples 1-2 in 25kGy electron beam irradiation, respectively taking 5g in a centrifuge tube, adding 10ml of physiological saline, simultaneously setting a negative control group and a positive control group, wherein 10ml of physiological saline is added in the centrifuge tube of the negative control group, 10ml of distilled water is added in the centrifuge tube of the positive control group, parallel experiments are carried out on the samples, the samples are placed in a constant-temperature water bath with the temperature of 37+/-0.5 ℃ for 30min, then 0.2ml of prepared diluted anticoagulated rabbit blood is respectively added in each centrifuge tube, slowly mixing is carried out, and the samples are kept in the constant-temperature water bath with the temperature of 37+/-0.5 ℃ for 60min. All the centrifuge tubes were removed, centrifuged for 5min at 3000rpm, 3ml of the supernatant was carefully aspirated, and the supernatant was placed in a spectrophotometer cuvette, and the absorbance at 545nm was measured with a spectrophotometer, and the hemolysis rate was expressed as a percentage as = (sample absorbance-negative control absorbance)/(positive control absorbance-negative control absorbance) ×100%. If the hemolysis rate is less than 5%, the material meets the hemolysis test requirement of the medical material.
TABLE 1 results of radiation resistant filler Performance test
| Uric acid adsorption Rate before irradiation | Uric acid adsorption Rate after irradiation | Rate of hemolysis/% | |
| Example 1 | 57.8％ | 51.7％ | 1.8 |
| Example 2 | 56.6％ | 49.9％ | 1.2 |
| Example 3 | 56.2％ | 49.3％ | 1.3 |
| Example 4 | 57.9％ | 52.8％ | 1.5 |
| Comparative example 1 | 42.1％ | 16.9％ | 2.6 |
| Comparative example 2 | 41.5％ | 18.2％ | 3.8 |
As can be seen from Table 1, the radiation-resistant filler (examples 1-4) for a blood perfusion device prepared by the invention has a good effect on the adsorption rate of uric acid after radiation sterilization, which indicates that the radiation-resistant filler prepared by the invention has good radiation resistance and can play a good role in protecting urate oxidase. In comparative example 1, no functional enzyme is added, and the irradiation resistance effect is obviously reduced; the immobilized enzyme reticular carrier particles prepared in comparative example 2, which are not prepared by the invention, cannot play a role in wrapping and protecting the urate oxidase, so that the activity of the urate oxidase is reduced, and the adsorption rate of uric acid is obviously reduced. And the radiation-resistant filler for the blood perfusion device, prepared by the invention, has good application prospect, and the hemolysis rate of the radiation-resistant filler after irradiation reaches the national standard.
Although embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made therein without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (5)
1. A method of preparing an irradiation-resistant filler for a blood perfusion apparatus, comprising the steps of:
(1) Preparation of zinc melamine salicylate hydrogel: adding deionized water into a beaker, then adding zinc sulfate, melamine and salicylic acid, fully and uniformly mixing, carrying out constant-temperature oscillation reaction, and cooling to room temperature after the reaction is completed to obtain melamine zinc salicylate hydrogel;
(2) Preparation of hydrogel particles: adding n-hexane and sorbitan trioleate into a beaker, then adding the zinc melamine salicylate hydrogel obtained in the step (1), and carrying out stirring reaction to obtain a hydrogel particle mixed solution after the reaction is completed;
(3) Immobilized enzyme network carrier particles: adding 2-methylimidazole into the hydrogel particle mixed solution obtained in the step (2), oscillating at constant temperature, cooling to room temperature after the oscillating is completed, and performing filtration, washing and drying treatment to obtain a particle product; then adding the granular product into deionized water, soaking at constant temperature, and then filtering and drying to obtain immobilized enzyme reticular carrier particles;
(4) Preparation of radiation-resistant filler: adding the immobilized enzyme reticular carrier particles obtained in the step (3) into Tris buffer solution, then adding urate oxidase and functional enzyme for constant-temperature oscillation, and then filtering and drying to obtain the radiation-resistant filler;
wherein the pH of the Tris buffer in step (4) is 8.0-9.0; the functional enzyme is one or more of superoxide dismutase and catalase; the mass ratio of the immobilized enzyme reticular carrier particles to the Tris buffer solution to the urate oxidase to the functional enzyme is 50:100-150:0.01-0.03:0.01-0.02; the constant-temperature oscillation temperature is 30-40 ℃ and the oscillation time is 2-4h;
in the step (1), the mass ratio of the zinc sulfate to the melamine to the salicylic acid to the deionized water is 10-20:70-90:20-40:800-1000;
the mass ratio of the n-hexane, sorbitan trioleate and zinc melamine salicylate hydrogel in the step (2) is 130-200:3-8:900-1140;
the mass ratio of the 2-methylimidazole to the hydrogel particle mixed solution in the step (3) is 4-8:1000-1400.
2. The method for preparing radiation-resistant filler for hemoperfusion apparatus as claimed in claim 1, wherein the reaction temperature of the constant temperature oscillation reaction in step (1) is 65-90 ℃ and the reaction time is 2-4h.
3. The method for preparing radiation-resistant filler for hemoperfusion apparatus as claimed in claim 1, wherein the stirring reaction temperature in step (2) is 50-70 ℃, the reaction time is 2-4h, and the stirring speed is 150-250r/min.
4. The method for preparing radiation-resistant filler for hemoperfusion apparatus as claimed in claim 1, wherein the constant temperature oscillation temperature in step (3) is 60-70 ℃ and the oscillation time is 1-2h; the constant-temperature soaking temperature is 70-90 ℃ and the soaking time is 12-18h.
5. An irradiation resistant filler for a blood perfusion device prepared by the method of any one of claims 1-4.
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| Hierarchical Micro- and Mesoporous Zn-Based Metal–Organic Frameworks Templated by Hydrogels: Their Use for Enzyme Immobilization and Catalysis of Knoevenagel Reaction;Kaipeng Cheng 等;Small;第15卷;文章号: 1902927, 1906245 * |
| 抗氧化物质在辐射防护中的作用;张春生 等;中国工业医学杂志;第16卷(第4期);222-224 * |
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