Modified filler for blood perfusion and preparation method thereof

Abstract

The invention relates to the technical field of blood perfusion, in particular to a modified filler for blood perfusion and a preparation method thereof.The preparation method comprises the steps that S1, pretreated polystyrene resin is subjected to argon plasma coating, and plasma coating resin is obtained; s2, adding plasma coating resin into an acrylic acid solution, and performing ultraviolet irradiation to obtain modified plasma coating resin; s3, dispersing 6-monoamino-beta-cyclodextrin in an ethanol aqueous solution, adding phenyl isothiocyanate and triethylamine, and carrying out a reaction to obtain modified cyclodextrin; and S4, uniformly mixing the modified cyclodextrin, the modified plasma coating resin and monopotassium phosphate in deionized water, carrying out heating reaction, and after the reaction is finished, washing and drying to obtain the modified filler for blood perfusion. The modified filler for blood perfusion prepared by the invention can improve the removal rate of uric acid, has little influence on other substance components in blood, and has stronger specificity.

Description

Technical Field

[0001] The present invention relates to the technical field of blood perfusion, and in particular to a modified filler for blood perfusion and a preparation method thereof. Background Art

[0002] Hyperuricemia is a common metabolic disease, which is mainly caused by excessive production of uric acid in the body and insufficient excretion. The causes of excessive uric acid production in the body include congenital abnormalities in purine metabolism, as well as secondary excessive uric acid production caused by kidney disease and myeloproliferative diseases. Reduced glomerular filtration rate, increased tubular reabsorption, and tubular secretion dysfunction are the main causes of reduced uric acid excretion. Long-term hyperuricemia can cause acute gouty arthritis, form uric acid stones in the urinary system, and cause renal colic, hematuria, and acute renal failure after obstruction. Oral medication is currently the main treatment for hyperuricemia. It reduces uric acid production, promotes uric acid excretion, and inhibits uric acid reabsorption to reduce uric acid concentration in the body to achieve the purpose of treatment. However, the efficacy of these drugs is unstable, individual differences are obvious, and the toxic and side effects of some drugs are difficult to avoid, especially the impact on liver and kidney function. These factors limit clinical treatment.

[0003] Hemoperfusion is a blood purification technology that introduces the patient's blood into a perfusion device filled with solid adsorbents, and removes exogenous or endogenous toxins, drugs or metabolites in the blood that cannot be removed by dialysis through adsorption. It is mainly used to rescue drug and poison poisoning, and can also be used in combination with hemodialysis to remove macromolecular toxins in patients with chronic renal failure who are undergoing maintenance dialysis. Since the solid adsorbents filled inside are made of polystyrene resin or activated carbon, most of them currently rely on direct supply from suppliers, and users have less independent research and development. The types of substances that can be adsorbed by the adsorbents are limited, and the molecular weight of the adsorbed substances cannot be more accurately controlled, making the hemoperfusion device mostly non-specific adsorption. During the clinical use of hemoperfusion devices, it often happens that while certain pathogenic substances are effectively adsorbed, other body fluid components with similar molecular weights are also adsorbed, resulting in the loss of beneficial body fluid components in the human body, causing some potential health risks.

[0004] At present, some users have made different degrees of modification and reprocessing on solid adsorbents, but the filler substrate is still limited to the product attributes of the resin supplier itself, which makes it difficult to flexibly choose in actual clinical applications. At the same time, the adsorbent filler substrates provided by most existing adsorbent suppliers have large batch differences, unstable biocompatibility, incomplete contact between the filler and harmful substances in the blood, and low adsorption efficiency. In addition, the modification or modification methods in the prior art will introduce a variety of chemical reagents when modifying the chemical bonds of the resin. Some reagents are toxic and harmful or have unstable chemical properties, and the problem of biocompatibility has not been well solved. Summary of the invention

[0005] In view of this, the present invention proposes a modified filler for blood perfusion and a preparation method thereof, so as to solve the problems of low adsorption efficiency and poor biocompatibility of resin adsorbents in blood perfusion in the prior art.

[0006] The technical solution of the present invention is achieved in this way:

[0007] In a first aspect, the present invention provides a method for preparing a modified filler for blood perfusion, comprising the following preparation steps:

[0008] S1, subjecting a polystyrene resin to ultrasonic pretreatment, placing the pretreated polystyrene resin in a plasma coating machine, and subjecting the polystyrene resin to argon plasma coating. After the coating is completed, the polystyrene resin is exposed to air for a reaction of 25-35 minutes to obtain a plasma coating resin;

[0009] S2, adding the plasma coating resin to the acrylic acid solution, and irradiating the solution with ultraviolet light to obtain a modified plasma coating resin;

[0010] S3, dispersing 6-monoamino-β-cyclodextrin in an ethanol aqueous solution, adding phenyl isothiocyanate and triethylamine, reacting at room temperature for 20-24 hours, and after the reaction is completed, vacuum rotary evaporation, and separating the obtained solid with a silica gel column, using ethyl acetate as the eluent, to obtain modified cyclodextrin;

[0011] S4. Evenly mix the modified cyclodextrin, modified plasma coating resin and potassium dihydrogen phosphate in deionized water, heat at 130-140° C. for reaction for 3-4 hours, and after the reaction is completed, wash and dry to obtain the modified filler for blood perfusion.

[0012] In the present invention, acrylic acid is grafted onto the surface of the resin filler by plasma plating and ultraviolet light induction to improve the selective adsorption of uric acid. 6-monoamino-β-cyclodextrin reacts with phenyl isothiocyanate to form a modified cyclodextrin containing a thiourea group, which further increases the affinity for uric acid. The modified cyclodextrin is fixed on the resin surface, and the synergistic effect between the cyclodextrin, the thiourea group and the polyacrylic acid greatly improves the adsorption capacity of the filler for uric acid. The modified filler for blood perfusion prepared by the present invention has multiple mechanisms of physical adsorption and chemical adsorption, and the filler has a significantly enhanced ability to remove uric acid.

[0013] On the basis of the above technical solution, preferably, the ultrasonic pretreatment in step S1 includes: ultrasonically cleaning the polystyrene resin with anhydrous ethanol, and the mass volume ratio of the polystyrene resin to the anhydrous ethanol is 3g:3-5mL.

[0014] Based on the above technical solution, preferably, the particle size of the polystyrene resin is 0.5-1.2 mm; the pore size is 2-6 nm, and the specific surface area is ≥1200 m 2 / g, pore volume ≥0.9mL / g, wet apparent density 0.7-0.8g / mL.

[0015] Compared with traditional macroporous resins, polystyrene resins do not have a macroporous structure and do not rely on the adsorption of the macroporous resin itself. Instead, they achieve affinity for substances such as uric acid through surface modification. This structural feature helps to improve hemodynamics and reduce the risk of thrombosis.

[0016] On the basis of the above technical solution, preferably, the argon plasma coating in step S1 includes the following steps: placing the pretreated polystyrene resin in a plasma coating machine, and when the vacuum degree reaches 5×10 -3 Pa, nitrogen was introduced into the ion source at a flow rate of 0.7-0.8 L / min for 15-25 min, the temperature was heated to 130-170 °C, and then the nitrogen was stopped, the plasma power was turned on, and argon was continuously introduced until the vacuum degree reached 4 × 10 -2 Pa, then adjust the ion current to 70-80A, the voltage to 150V, and the coating time to 15-20min.

[0017] On the basis of the above technical solution, preferably, in step S2, the mass volume ratio of the plasma coating resin and the acrylic acid solution is 3g:3-5mL, the concentration of the acrylic acid solution is 0.2-0.3mol / L, the power during ultraviolet irradiation is 25-35W, and the wavelength is 365nm.

[0018] First, high-energy argon plasma is used to bombard the resin surface to produce physical sputtering and form a highly active film. Argon plasma can remove inert groups on the resin surface, generate free radicals or active sites, and provide active groups for subsequent reactions; after 25-35 minutes of contact with air, the active sites on the resin surface react with oxygen, introducing oxygen-containing functional groups to increase the hydrophilicity and reactivity of the resin surface. Then, acrylic acid is grafted onto the surface of the resin filler by ultraviolet light induction to form a polyacrylic acid layer on the resin surface, increasing the affinity for uric acid; at the same time, the carboxyl group forms a hydrogen bond with the carbonyl group of uric acid to improve the selective adsorption of uric acid.

[0019] On the basis of the above technical solution, preferably, in step S3, the mass ratio of 6-monoamino-β-cyclodextrin, phenyl isothiocyanate and triethylamine is 1:1.2-1.5:1.5-2.

[0020] Modified cyclodextrin containing thiourea groups is formed by the reaction of 6-monoamino-β-cyclodextrin and phenyl isothiocyanate. Firstly, cyclodextrin has a cylindrical cavity structure, the size of which matches the size of uric acid molecules, and can effectively adsorb uric acid molecules through host-guest inclusion complexation; secondly, the thiourea group can form hydrogen bonds with the hydroxyl and nitrogen atoms in the uric acid molecules, further increasing the affinity for uric acid.

[0021] On the basis of the above technical solution, preferably, in step S4, the mass ratio of the modified cyclodextrin, the modified plasma coating resin and potassium dihydrogen phosphate is 1.8-2.2:1:0.4-0.6.

[0022] On the basis of the above technical solution, preferably, in step S4, the heating temperature is 130-140° C., and the heating reaction time is 3-4 h.

[0023] The modified cyclodextrin is grafted onto the surface of the modified plasma coating resin by esterification and cross-linking of the hydroxyl groups on the outer cavity of cyclodextrin with the carboxyl groups in the modified plasma coating resin. The above-mentioned esterification and cross-linking can maintain the complete cavity structure of cyclodextrin on the one hand, so that cyclodextrin can better adsorb uric acid molecules; on the other hand, cyclodextrin, thiourea groups and polyacrylic acid can work synergistically to greatly improve the adsorption capacity of the filler for uric acid.

[0024] In a second aspect, the present invention provides a modified filler for blood perfusion prepared by the preparation method described above.

[0025] In a third aspect, the present invention provides an application of a modified filler for blood perfusion, wherein the modified filler for blood perfusion is used in a blood perfusion device.

[0026] Compared with the prior art, the modified filler for blood perfusion and the preparation method thereof of the present invention have the following advantages:

[0027] Beneficial effects:

[0028] (1) The present invention uses a polystyrene resin without a macroporous structure as a substrate, and introduces cyclodextrin, thiourea groups and polyacrylic acid layers on the resin surface through multiple modifications, forming a unique synergistic adsorption mechanism: the cyclodextrin cavity provides a size-matched inclusion effect, and the polyacrylic acid carboxyl group and thiourea group provide hydrogen bonding sites. The multiple mechanisms synergistically significantly improve the adsorption efficiency; significantly improve the selective adsorption of uric acid, improve blood compatibility, reduce the risk of side effects, and are suitable for blood perfusion; at the same time, the entire preparation method is mild and controllable, no toxic reagents are required, and the product has good stability;

[0029] (2) The surface of polystyrene resin is modified by plasma coating technology to form a negatively charged film on the resin surface, which effectively improves the hydrophilicity and provides groups for grafting. The reaction process is pollution-free and has good biocompatibility. Polyacrylic acid is grafted on the surface of plasma-coated resin by ultraviolet light induction, introducing a large number of carboxyl functional groups into the filler, which gives it a specific affinity for uric acid molecules and can quickly and efficiently bind to the carbonyl group of uric acid in the blood, expanding the scope of indications of previous hemoperfusion devices and having a therapeutic effect on gout or hyperuricemia. In addition, the matrix resin has no macroporous structure and does not need to rely on the adsorption of the macroporous resin itself. The hemodynamics is more stable, thrombosis is reduced, and the risk of thrombosis in patients is reduced.

[0030] (3) The thiourea group was introduced into cyclodextrin to enhance the adsorption capacity of the filler for uric acid. The thiourea group not only retained the original cavity inclusion effect of cyclodextrin, but also further increased the affinity with uric acid molecules through hydrogen bonding, forming a synergistic effect with the polyacrylic acid layer on the resin surface, significantly improving the selective adsorption capacity of the filler for uric acid. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0032] Figure 1 The figure is a flow chart of the preparation of the modified filler for blood perfusion of the present invention;

[0033] Figure 2 This is a product diagram of the modified filler for blood perfusion of the present invention. DETAILED DESCRIPTION

[0034] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0035] Unless otherwise specified, the raw materials used in the following examples and comparative examples are all commercially available.

[0036] The particle size of polystyrene resin is 0.5-1.2mm, the pore size is 2-6nm, and the specific surface area is ≥1200m 2 / g, pore volume ≥0.9mL / g, wet apparent density 0.7-0.8g / mL; 6-monoamino-β-cyclodextrin was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.

[0037] Example 1

[0038] This embodiment provides a modified filler for blood perfusion and a preparation method thereof, such as Figure 1 As shown, the following steps are included:

[0039] S1, take 150g polystyrene resin and use 200mL anhydrous ethanol to ultrasonically clean for 20min, filter out and then use deionized water to ultrasonically clean for 3 times, filter out and then dry at room temperature to obtain the pretreated polystyrene resin for use;

[0040] 150g of pretreated polystyrene resin was evenly spread on a carrier plate 15cm away from the RF electrode in the reaction chamber of the plasma coating machine. Close the bell jar reaction chamber and all valves, turn on the vacuum pump, and when the vacuum degree of the body reaches 5×10 - 3 Pa, open the air inlet pipeline, and pass nitrogen into the ion source at a flow rate of 0.75L / min for 20min to exhaust all residual air in the resin gap, reaction chamber and pipeline. During the whole nitrogen flow process, the polystyrene resin on the carrier plate was heated to 150℃. After the temperature was constant, the nitrogen flow was turned off and the plasma power was turned on. At the same time, argon was continuously introduced until the vacuum degree of the body reached 4×10 -2 Pa, then the ion current is adjusted to 75A, the voltage is adjusted to 150V, the coating time is 18min, after the coating is completed, the plasma power supply, the air inlet pipeline and the vacuum pump are turned off, and the polystyrene resin sample is immediately taken out, laid flat at room temperature, and fully exposed to the air for oxidation reaction for 30min to obtain the plasma coating resin;

[0041] S2, prepare 200mL of 0.25mol / L acrylic acid solution, add all 150g of plasma coating resin into the solution, add 1.5g of 2,2-dimethoxy-2-phenylacetophenone, and oscillate and mix at a constant temperature of 25°C and 120rpm for 30min. During the oscillation process, the solution is fully irradiated with ultraviolet light with a power of 30W and a wavelength of 365nm. After the reaction is completed, the product is filtered out, washed several times with a phosphate buffer solution (50mM, pH 7.4), and then vacuum dried to obtain a modified plasma coating resin;

[0042] S3, 10g of 6-monoamino-β-cyclodextrin was dispersed in 200mL of ethanol aqueous solution (ethanol and water 2:1), 13.5g of phenyl isothiocyanate and 18g of triethylamine were added, and the reaction was carried out at room temperature for 22h. After the reaction was completed, the vacuum rotary evaporation was performed, and the obtained solid was separated by silica gel column, and the eluent was ethyl acetate to obtain modified cyclodextrin;

[0043] S4, 20g of modified cyclodextrin, 10g of modified plasma coating resin and 5g of potassium dihydrogen phosphate were mixed, 200mL of deionized water was added, and the mixture was heated at 135°C for 3.5h. After the reaction was completed, the product was washed with deionized water and vacuum dried to obtain a modified filler for blood perfusion (such as Figure 2 shown).

[0044] Example 2

[0045] This embodiment provides a modified filler for blood perfusion and a preparation method thereof, comprising the following steps:

[0046] S1, take 150g polystyrene resin and use 150mL anhydrous ethanol to ultrasonically clean for 25min, filter out and then use deionized water to ultrasonically clean for 3 times, filter out and then dry at room temperature to obtain the pretreated polystyrene resin for use;

[0047] 150g of pretreated polystyrene resin was evenly spread on a carrier plate 15cm away from the RF electrode in the reaction chamber of the plasma coating machine. Close the bell jar reaction chamber and all valves, turn on the vacuum pump, and when the vacuum degree of the body reaches 5×10 - 3 Pa, open the air inlet pipeline, and pass nitrogen into the ion source at a flow rate of 0.7L / min for 25min to exhaust all residual air in the resin gap, reaction chamber and pipeline. During the whole nitrogen flow process, the polystyrene resin on the carrier plate was heated to 140℃. After the temperature was constant, the nitrogen flow was turned off and the plasma power was turned on. At the same time, argon was continuously introduced until the vacuum degree of the body reached 4×10 -2 Pa, then the ion current is adjusted to 70A, the voltage is adjusted to 150V, the coating time is 20min, after the coating is completed, the plasma power supply, the air inlet pipeline and the vacuum pump are turned off, and the polystyrene resin sample is immediately taken out, laid flat at room temperature, and fully exposed to the air for oxidation reaction for 25min to obtain the plasma coating resin;

[0048] S2, prepare 250mL of 0.2mol / L acrylic acid solution, add all 150g of plasma coating resin into the solution, and oscillate and mix at a constant temperature of 25°C and 100rpm for 35min. During the oscillation process, the solution is fully irradiated with ultraviolet light with a power of 25W and a wavelength of 365nm. After the reaction is completed, the product is filtered out, washed several times with a phosphate buffer solution (50mM, pH 7.4), and then vacuum dried to obtain a modified plasma coating resin;

[0049] S3, 10g of 6-monoamino-β-cyclodextrin was dispersed in 200mL of ethanol aqueous solution (ethanol and water 2:1), 12g of phenyl isothiocyanate and 15g of triethylamine were added, and the reaction was carried out at room temperature for 20h. After the reaction was completed, the vacuum rotary evaporation was performed, and the obtained solid was separated by silica gel column, and the eluent was ethyl acetate to obtain modified cyclodextrin;

[0050] S4. Mix 18 g of modified cyclodextrin, 10 g of modified plasma coating resin and 5 g of potassium dihydrogen phosphate, add 200 mL of deionized water, and heat to react at 130° C. for 4 h. After the reaction is completed, wash the product with deionized water and vacuum dry to obtain a modified filler for blood perfusion.

[0051] Example 3

[0052] This embodiment provides a modified filler for blood perfusion and a preparation method thereof, comprising the following steps:

[0053] S1, take 150g polystyrene resin and use 250mL anhydrous ethanol to ultrasonically clean for 15min, filter out and then use deionized water to ultrasonically clean for 3 times, filter out and then dry at room temperature to obtain the pretreated polystyrene resin for use;

[0054] 150g of pretreated polystyrene resin was evenly spread on a carrier plate 15cm away from the RF electrode in the reaction chamber of the plasma coating machine. Close the bell jar reaction chamber and all valves, turn on the vacuum pump, and when the vacuum degree of the body reaches 5×10 - 3 Pa, open the air inlet pipeline, and pass nitrogen into the ion source at a flow rate of 0.8L / min for 15min to exhaust all residual air in the resin gap, reaction chamber and pipeline. During the whole nitrogen flow process, the polystyrene resin on the carrier plate was heated to 160℃. After the temperature was constant, the nitrogen flow was turned off and the plasma power was turned on. At the same time, argon was continuously introduced until the vacuum degree of the body reached 4×10 -2 Pa, then the ion current is adjusted to 80A, the voltage is adjusted to 150V, the coating time is 15min, after the coating is completed, the plasma power supply, the air inlet pipeline and the vacuum pump are turned off, and the polystyrene resin sample is immediately taken out, laid flat at room temperature, and fully exposed to the air for oxidation reaction for 35min to obtain the plasma coating resin;

[0055] S2, prepare 150mL of 0.3mol / L acrylic acid solution, add all 150g of plasma coating resin into the solution, and oscillate and mix at a constant temperature of 25°C and 120rpm for 25min. During the oscillation process, the solution is fully irradiated with ultraviolet light with a power of 35W and a wavelength of 365nm. After the reaction is completed, the product is filtered out, washed several times with a phosphate buffer solution (50mM, pH 7.4), and then vacuum dried to obtain a modified plasma coating resin;

[0056] S3, 10g of 6-monoamino-β-cyclodextrin was dispersed in 200mL of ethanol aqueous solution (ethanol and water 2:1), 15g of phenyl isothiocyanate and 20g of triethylamine were added, and the reaction was carried out at room temperature for 24h. After the reaction was completed, the vacuum rotary evaporation was performed, and the obtained solid was separated by silica gel column, and the eluent was ethyl acetate to obtain modified cyclodextrin;

[0057] S4. Mix 22 g of modified cyclodextrin, 100 g of modified plasma coating resin and 6 g of potassium dihydrogen phosphate, add 200 mL of deionized water, and heat to react at 140° C. for 3 h. After the reaction, wash the product with deionized water and vacuum dry to obtain a modified filler for blood perfusion.

[0058] Example 4

[0059] This embodiment provides a modified filler for blood perfusion and a preparation method thereof, comprising the following steps:

[0060] S1, take 150g polystyrene resin and use 180mL anhydrous ethanol to ultrasonically clean for 22min, filter out and then use deionized water to ultrasonically clean for 3 times, filter out and then dry at room temperature to obtain the pretreated polystyrene resin for use;

[0061] 150g of pretreated polystyrene resin was evenly spread on a carrier plate 15cm away from the RF electrode in the reaction chamber of the plasma coating machine. Close the bell jar reaction chamber and all valves, turn on the vacuum pump, and when the vacuum degree of the body reaches 5×10 - 3 Pa, open the air inlet pipeline, and pass nitrogen into the ion source at a flow rate of 0.77L / min for 18min to exhaust all residual air in the resin gap, reaction chamber and pipeline. During the whole nitrogen flow process, the polystyrene resin on the carrier plate was heated to 145℃. After the temperature was constant, the nitrogen flow was turned off and the plasma power was turned on. At the same time, argon was continuously introduced until the vacuum degree of the body reached 4×10 -2 Pa, then the ion current is adjusted to 75A, the voltage is adjusted to 150V, the coating time is 16min, after the coating is completed, the plasma power supply, the air inlet pipeline and the vacuum pump are turned off, and the polystyrene resin sample is immediately taken out, laid flat at room temperature, and fully exposed to the air for oxidation reaction for 28min to obtain the plasma coating resin;

[0062] S2, prepare 220mL of 0.22mol / L acrylic acid solution, add all 150g of plasma coating resin into the solution, and oscillate and mix at a constant temperature of 25°C and 120rpm for 24min. During the oscillation process, the solution is fully irradiated with ultraviolet light with a power of 30W and a wavelength of 365nm. After the reaction is completed, the product is filtered out, washed several times with a phosphate buffer solution (50mM, pH 7.4), and then vacuum dried to obtain a modified plasma coating resin;

[0063] S3, 10g of 6-monoamino-β-cyclodextrin was dispersed in 200mL of ethanol aqueous solution (ethanol and water 2:1), 12.5g of phenyl isothiocyanate and 16g of triethylamine were added, and the reaction was carried out at room temperature for 23h. After the reaction was completed, the vacuum rotary evaporation was performed, and the obtained solid was separated by silica gel column, and the eluent was ethyl acetate to obtain modified cyclodextrin;

[0064] S4. Mix 19 g of modified cyclodextrin, 10 g of modified plasma coating resin and 5.5 g of potassium dihydrogen phosphate, add 200 mL of deionized water, and heat to react at 130°C for 3.5 h. After the reaction, wash the product with deionized water and vacuum dry to obtain a modified filler for blood perfusion.

[0065] Comparative Example 1

[0066] This embodiment provides a modified filler for blood perfusion and a preparation method thereof, comprising the following steps:

[0067] S1, take 150g polystyrene resin and use 200mL anhydrous ethanol to ultrasonically clean for 20min, filter out and then use deionized water to ultrasonically clean for 3 times, filter out and then dry at room temperature to obtain the pretreated polystyrene resin for use;

[0068] 150g of pretreated polystyrene resin was evenly spread on a carrier plate 15cm away from the RF electrode in the reaction chamber of the plasma coating machine. Close the bell jar reaction chamber and all valves, turn on the vacuum pump, and when the vacuum degree of the body reaches 5×10 - 3 Pa, open the air inlet pipeline, and pass nitrogen into the ion source at a flow rate of 0.75L / min for 20min to exhaust all residual air in the resin gap, reaction chamber and pipeline. During the whole nitrogen flow process, the polystyrene resin on the carrier plate was heated to 150℃. After the temperature was constant, the nitrogen flow was turned off and the plasma power was turned on. At the same time, argon was continuously introduced until the vacuum degree of the body reached 4×10 -2 Pa, then the ion current is adjusted to 75A, the voltage is adjusted to 150V, the coating time is 18min, after the coating is completed, the plasma power supply, the air inlet pipeline and the vacuum pump are turned off, and the polystyrene resin sample is immediately taken out, laid flat at room temperature, and fully exposed to the air for oxidation reaction for 30min to obtain the plasma coating resin;

[0069] S2, prepare 200mL of 0.25mol / L acrylic acid solution, add all 150g of plasma coating resin into the solution, and oscillate and mix at a constant temperature of 25°C and 120rpm for 30min. During the oscillation process, the solution is fully irradiated with ultraviolet light with a power of 30W and a wavelength of 365nm. After the reaction is completed, the product is filtered out, washed several times with a phosphate buffer solution (50mM, pH 7.4), and then vacuum dried to obtain a modified plasma coating resin;

[0070] S3. Mix 20 g of cyclodextrin, 10 g of modified plasma coating resin and 5 g of potassium dihydrogen phosphate, add 200 mL of deionized water, and heat to react at 135° C. for 3.5 h. After the reaction is completed, the product is washed with deionized water and vacuum dried to obtain a modified filler for blood perfusion.

[0071] Comparative Example 2

[0072] This embodiment provides a modified filler for blood perfusion and a preparation method thereof, comprising the following steps:

[0073] S1, take 150g polystyrene resin and use 200mL anhydrous ethanol to ultrasonically clean for 20min, filter out and then use deionized water to ultrasonically clean for 3 times, filter out and then dry at room temperature to obtain the pretreated polystyrene resin for use;

[0074] 150g of pretreated polystyrene resin was evenly spread on a carrier plate 15cm away from the RF electrode in the reaction chamber of the plasma coating machine. Close the bell jar reaction chamber and all valves, turn on the vacuum pump, and when the vacuum degree of the body reaches 5×10 - 3 Pa, open the air inlet pipeline, and pass nitrogen into the ion source at a flow rate of 0.75L / min for 20min to exhaust all residual air in the resin gap, reaction chamber and pipeline. During the whole nitrogen flow process, the polystyrene resin on the carrier plate was heated to 150℃. After the temperature was constant, the nitrogen flow was turned off and the plasma power was turned on. At the same time, argon was continuously introduced until the vacuum degree of the body reached 4×10 -2 Pa, then the ion current is adjusted to 75A, the voltage is adjusted to 150V, the coating time is 18min, after the coating is completed, the plasma power supply, the air inlet pipeline and the vacuum pump are turned off, and the polystyrene resin sample is immediately taken out, laid flat at room temperature, and fully exposed to the air for oxidation reaction for 30min to obtain the plasma coating resin;

[0075] S2, 10g of 6-monoamino-β-cyclodextrin was dispersed in 200mL of ethanol aqueous solution (ethanol and water 2:1), 13.5g of phenyl isothiocyanate and 18g of triethylamine were added, and the reaction was carried out at room temperature for 22h. After the reaction was completed, the vacuum rotary evaporation was performed, and the obtained solid was separated by silica gel column, and the eluent was ethyl acetate to obtain modified cyclodextrin;

[0076] S3. Mix 20 g of modified cyclodextrin, 10 g of modified plasma coating resin and 5 g of potassium dihydrogen phosphate, add 200 mL of deionized water, and heat to react at 135° C. for 3.5 h. After the reaction is completed, wash the product with deionized water and vacuum dry to obtain a modified filler for blood perfusion.

[0077] Performance Testing

[0078] The modified filler obtained by Example 1-4 and Comparative Example 1-2 is weighed 50g and applied to 6 blood perfusion devices respectively. The upper and lower ends of each blood perfusion device are connected to two containers by pipelines respectively, and untreated plasma is held in the container at the upper end, and the container at the lower end is used to receive the plasma after being processed by the blood perfusion device, and the pipeline between the container at the upper end and the blood perfusion device is equipped with a peristaltic pump, providing power so that blood plasma can flow into the blood perfusion device. Then carry out blood perfusion effect test, test uric acid concentration in blood before and after perfusion, and detect uric acid concentration using commercially available uric acid content determination kit (Beijing Suolebao Technology Co., Ltd., article number E-BC-F018), and test result is as shown in Table 1.

[0079] Table 1 Uric acid clearance rate

[0080]

[0081] It can be seen from Table 1 that the modified filler for hemoperfusion prepared by the present invention is applied to a hemoperfusion device, which can increase the clearance rate of uric acid in the blood to more than 40%, thereby greatly improving the clearance rate of uric acid.

[0082] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing a modified filler for blood perfusion, characterized in that: The method comprises the following preparation steps: S1, subjecting a polystyrene resin to ultrasonic pretreatment, placing the pretreated polystyrene resin in a plasma coating machine, and subjecting the polystyrene resin to argon plasma coating. After the coating is completed, the polystyrene resin is exposed to air for a reaction of 25-35 minutes to obtain a plasma coating resin; S2, adding the plasma coating resin to the acrylic acid solution, and irradiating the solution with ultraviolet light to obtain a modified plasma coating resin; S3, dispersing 6-monoamino-β-cyclodextrin in an ethanol aqueous solution, adding phenyl isothiocyanate and triethylamine, reacting at room temperature for 20-24 hours, and performing vacuum rotary evaporation. The obtained solid was separated by a silica gel column with ethyl acetate as the eluent to obtain a modified cyclodextrin; S4, uniformly mixing the modified cyclodextrin, the modified plasma coating resin and potassium dihydrogen phosphate in deionized water, heating for reaction, and after the reaction is completed, washing and drying to obtain the modified filler for blood perfusion.

2. The method for preparing a modified filler for blood perfusion according to claim 1, characterized in that: The ultrasonic pretreatment in step S1 includes: ultrasonically cleaning the polystyrene resin with anhydrous ethanol, the mass volume ratio of the polystyrene resin to the anhydrous ethanol is 3g:3-5mL, and the ultrasonic cleaning time is 15-25min.

3. The method for preparing a modified filler for blood perfusion according to claim 1, characterized in that: The argon plasma coating in step S1 includes the following steps: placing the pretreated polystyrene resin in a plasma coating machine, and when the vacuum degree reaches 5×10 -3 Pa, nitrogen was introduced into the ion source at a flow rate of 0.7-0.8 L / min for 15-25 min, the temperature was heated to 130-170 °C, and then the nitrogen was stopped, the plasma power was turned on, and argon was continuously introduced until the vacuum degree reached 4 × 10 -2 Pa, then adjust the ion current to 70-80A, the voltage to 150V, and the coating time to 15-20min.

4. The method for preparing a modified filler for blood perfusion according to claim 1, characterized in that: In step S2, the mass volume ratio of the plasma coating resin and the acrylic acid solution is 3g:3-5mL, and the concentration of the acrylic acid solution is 0.2-0.3mol / L.

5. The method for preparing a modified filler for blood perfusion according to claim 1, characterized in that: In step S2, the power during ultraviolet light irradiation is 25-35W and the wavelength is 365nm.

6. The method for preparing a modified filler for blood perfusion according to claim 1, characterized in that: In step S3, the mass ratio of 6-monoamino-β-cyclodextrin, phenyl isothiocyanate and triethylamine is 1:1.2-1.5:1.5-2.

7. The method for preparing a modified filler for blood perfusion according to claim 1, characterized in that: In step S4, the mass ratio of modified cyclodextrin, modified plasma coating resin and potassium dihydrogen phosphate is 1.8-2.2:1:0.4-0.

6.

8. The method for preparing a modified filler for blood perfusion according to claim 1, characterized in that: In step S4, the heating temperature is 130-140° C., and the heating reaction time is 3-4 hours.

9. A modified filler for blood perfusion prepared by the preparation method according to any one of claims 1 to 8.

10. The use of a modified filler for blood perfusion according to claim 9, characterized in that: The modified filler for blood perfusion is used in a blood perfusion device.

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