CN111978590B

CN111978590B - Zeolite-heparin mimic polymer blending microsphere as well as preparation method and application thereof

Info

Publication number: CN111978590B
Application number: CN202010920218.4A
Authority: CN
Inventors: 邱逦; 王周君; 赵长生; 赵伟锋
Original assignee: Sichuan University
Current assignee: Sichuan University
Priority date: 2020-09-04
Filing date: 2020-09-04
Publication date: 2021-02-12
Anticipated expiration: 2040-09-04
Also published as: CN111978590A

Abstract

The invention discloses a zeolite-heparin mimic polymer blending microsphere, which belongs to the technical field of biological materials and comprises the following components in parts by weight (65-85): (12-32): (1-5) carrying out free radical polymerization on the monomers in the polyether sulfone solution to obtain a heparin-simulated polymer, adding zeolite powder, carrying out ultrasonic dispersion on the heparin-simulated polymer uniformly, and carrying out phase separation on the mixed solution in a coagulating bath to form microspheres; the zeolite-heparin mimic polymer blending microsphere has the capability of selectively adsorbing potassium ions in blood and aqueous solution, and has anticoagulation property and good blood compatibility when contacting with blood; the adsorbent can be applied to blood purification treatment, can be used as a high-efficiency adsorbent, and provides a high-efficiency and safe treatment scheme for patients with hyperkalemia; and the raw materials are simple and easy to obtain, the microsphere can be prepared in a large amount by chemical engineering, the preparation process of the microsphere is simple, and industrial mass production is easy to realize.

Description

Zeolite-heparin mimic polymer blending microsphere as well as preparation method and application thereof

Technical Field

The invention relates to the technical field of biological materials, in particular to zeolite-heparin mimic polymer blending microspheres as well as a preparation method and application thereof.

Background

Hyperkalemia is a potential and serious electrolyte disorder, describing blood potassium levels that are very high by 5.5 mmol/L. Since the kidney plays a key role in potassium ion balance, chronic kidney disease patients have a higher probability of hyperkalemia and will also suffer more serious consequences than normal patients. Hyperkalemia is associated with a significant increase in mortality, fatal cardiac arrhythmias, and limited use of inhibitors of the renin-angiotensin-aldosterone system. Routes to remove excess blood potassium include redistribution intracellularly, clearance through the kidney and gastrointestinal tract, and extracorporeal blood purification clearance. In blood purification therapy, traditional hemodialysis remains the decisive strategy, which is based on a gradient in potassium concentration between the blood and the low-potassium dialysate as the driving force for ion diffusion. The wearable artificial kidney eliminates the dependence on a fixed hemodialysis machine, reduces the burden of daily life of a patient, and still cannot solve the problem of dialysate regeneration. Blood perfusion based on adsorbents can rapidly remove toxins, but no adsorbent with good selectivity and blood compatibility for potassium is available, which is a major challenge facing the present.

The zeolite, sodium zirconium cyclosilicate, layered phosphate, carbon-based material, polymer material, crown ether and graphene derivatives thereof and other various reagents have selective ion exchange/detection/storage capacity. Zeolites are desirable materials from the standpoint of production cost and adsorption capacity. The boiling water acts as an aluminosilicate crystal whose interconnected micropores accommodate exchangeable cations to compensate for the negative charge of the framework. The contact of zeolite with blood in the form of powder has inevitable limitations, and leakage of minute particles is difficult to avoid and results in failure of blood purification. Better blood compatibility can be obtained by using polymer-zeolite composite materials, such as polymer-zeolite blend microspheres. The polyether sulfone is a good carrier for the micro-particles due to ideal mechanical and chemical stability, and can be used as a substrate of the microspheres. The use of biomolecules (e.g., surface heparinization, nitric oxide delivery) can provide desirable biocompatibility for heart stents, blood vessels, and other blood contacting materials. The heparin mimic polymer shows good blood compatibility and anticoagulation effect, and is expected to be used as a substitute of heparin for blood purification. These polymers may be beneficial in the treatment of hyperkalemia, as heparin itself is a risk factor for hyperkalemia, interfering with renal potassium excretion.

Therefore, the material provided by the invention has selective potassium ion removal capacity, good mechanical stability and ideal blood compatibility, is used as a blood purification adsorbent for hyperkalemia, and has great research significance and application prospect.

Disclosure of Invention

It is an object of the present invention to provide zeolite-heparin-like polymer blend microspheres to solve the above problems.

In order to achieve the purpose, the technical scheme adopted by the invention is as follows: a zeolite-heparin mimic polymer blending microsphere comprises the following components in parts by weight:

1) polyether sulfone solution:

6-12 parts of polyether sulfone

88-94 parts of organic solvent

2) Zeolite powder

3) Polymerization reaction stock solution:

55-75 parts of acrylic acid

10-30 parts of N-vinyl pyrrolidone

2-10 parts of oil-soluble azo initiator

2-15 parts of amide group-containing crosslinking agent

The weight ratio of the polyether sulfone solution to the zeolite powder to the polymerization reaction stock solution is (65-85): (12-32): (1-5).

As a preferred technical scheme: the organic solvent is at least one of dimethylformamide, dimethylacetamide or dimethyl sulfoxide.

As a preferred technical scheme: the zeolite powder is LTA type, LAU type, HEU type or MOR type, and preferably LTA type.

As a preferred technical scheme: the oil-soluble azo initiator is azobisisobutyronitrile.

As a preferred technical scheme: the amide group-containing cross-linking agent is N, N' -methylenebisacrylamide.

The second objective of the present invention is to provide a preparation method of the zeolite-heparin mimic polymer blend microsphere, which comprises the following steps:

1) preparation of polyether sulfone solution

Weighing 6-12 parts of polyether sulfone quantitatively, dissolving in 88-94 parts of organic solvent, stirring and dissolving for 12-24 hours to obtain a polyether sulfone solution;

2) preparation of heparin analogue polymer solution

Weighing 55-75 parts of acrylic acid, 10-30 parts of N-vinyl pyrrolidone, 2-10 parts of oil-soluble azo initiator and 2-15 parts of cross-linking agent containing amide group quantitatively, according to the polyether sulfone solution: the heparin analogue polymer stock solution is (65-85): (1-5), adding the prepared polyether sulfone solution, stirring and heating at 80-120 ℃ for 12-36 hours, and performing free radical polymerization to obtain a heparin analogue polymer solution;

3) formulation of Zeolite-heparin mimetic Polymer suspensions

According to the polyether sulfone solution: the zeolite is (65-85): (12-32), weighing zeolite powder, adding the prepared heparin-simulated polymer solution, stirring at room temperature for 2-6 hours, ultrasonically dispersing for 1-4 hours, and defoaming under negative pressure for 0.5-1 hour to obtain a zeolite-heparin-simulated polymer suspension;

4) preparation of microsphere zeolite-heparin analogue polymer blending microsphere

Pumping the zeolite-heparin analogue polymer suspension into an injector with the specification of 1-20 mL, pushing the injector into an electrostatic field, so that the suspension forms tiny liquid drops in the air, and the liquid drops fall into a coagulating bath for phase conversion to form microspheres with uniform size.

As a preferred technical scheme: in the step 4), the electrostatic field is formed through an electrostatic spinning machine.

As a preferred technical scheme: in the step 4), the diameter of the microsphere is controlled to be 200-2000 μm by adjusting the electrostatic voltage, the aperture of the syringe needle or the injection speed.

The third purpose of the invention is to provide the application of the zeolite-heparin simulating polymer blended microspheres in the preparation of blood purifying devices.

As a preferred technical scheme: the blood purification is hyperkalemia blood purification.

The preparation method comprises the steps of preparing a polyether sulfone solution, adding the polymerization reaction stock solution into the polyether sulfone solution according to a proper proportion, uniformly mixing and heating. The heparin analogue polymer crosslinked in situ is synthesized by free radical polymerization. Adding zeolite powder, and ultrasonically dispersing uniformly. The blended microspheres were prepared by electrostatic spraying and phase separation.

The preparation method is simple and convenient, is convenient to operate, has wide monomer sources, and does not need further chemical modification. Ion adsorption materials in the prior art often do not have good blood compatibility and cannot be directly used for blood purification. The method of the invention utilizes simple free radical polymerization, ultrasonic dispersion and phase separation to form spheres. The heparin mimic polymer is used for realizing ideal blood compatibility and anticoagulation effect, is synthesized by free radical polymerization, and has the following mechanism:

an oil-soluble azo initiator such as azobisisobutyronitrile initiates free radical polymerization of acrylic monomers and N-vinyl pyrrolidone monomers under heating. Under the participation of an amide-group-containing cross-linking agent such as N, N' -methylene bisacrylamide, the generated cross-linked hydrophilic copolymer molecules are entangled with the long chains of polyether sulfone molecules to form an in-situ cross-linked polymer network. Wherein the reaction formula of the hydrophilic copolymer obtained by free radical polymerization of the monomers is as follows:

the added zeolite powder is fully mixed with the polymer solution and then phase-separated to form microspheres, and the particles are uniformly dispersed and fixed in a porous polymer matrix to provide the microspheres with selective potassium ion removal capability.

The zeolite-heparin mimic polymer blending microsphere has the selective potassium ion adsorption capacity mainly based on the specific ion exchange function of zeolite powder added in the zeolite-heparin mimic polymer blending microsphere, and specifically comprises the following components in percentage by weight: in human blood, Na⁺And K⁺Is the highest of all cations. And under normal conditions, Na⁺(135-145mmol/L) is K⁺Several tens times of (3.5-5.5 mmol/L). Thus, derived from Na⁺Ion competition of (a) is a primary concern for selective potassium ion scavenging.

The inventor takes a Na-LTA zeolite powder added zeolite-heparin mimic polymer blend microsphere as an example, and the initial concentration is Na⁺＝145mmol/L、K⁺When the microspheres were adsorbed in an aqueous solution of 10mmol/L at 37 ℃ for two hours, the adsorption amount of potassium ions was 0.5mmol/g, and the absolute value of the fluctuation in the sodium ion concentration was less than 0.2 mmol/g. This adsorption result may indicate the selective potassium ion scavenging ability of the microspheres, considering the large concentration difference of the two ions in blood.

The invention has the greatest characteristic that the heparin analogue polymer is synthesized by utilizing the free radical polymerization reaction, the blood compatibility of the blending microsphere is improved, the microsphere keeps the selective potassium ion removing capability similar to zeolite powder, and the microsphere prepared by the method has lower cost and superior performance.

By adopting the method, the swelling ratio of the microsphere material prepared by the invention is lower than 300% in a normal saline environment; the adsorption capacity of the microspheres to potassium ions is 40-100 mg/g; the microspheres have a hemolysis rate of not more than 1%.

Compared with the prior art, the invention has the advantages that:

1. the zeolite-heparin mimic polymer blending microsphere has the capability of selectively adsorbing potassium ions and excellent blood compatibility;

2. the microsphere can be used for blood purification and can reduce the blood potassium level of patients with hyperkalemia;

3. the heparin analogue polymer contained in the microsphere prepared by the invention is generated by free radical polymerization, so that the blood compatibility of the microsphere is improved;

4. the zeolite particles contained in the microsphere prepared by the invention have wide selection range, and some commercialized zeolites can meet the selective potassium ion removal capacity required by the microsphere;

5. the microsphere prepared by the invention has a porous structure and good hydrophilicity, and can quickly reduce the concentration of potassium ions;

6. the raw materials used by the microsphere prepared by the invention are common chemical raw materials, can be prepared in a large scale by chemical industry, have rich resources and low cost, and are beneficial to industrialization.

Drawings

FIG. 1 is a scanning electron microscope image of a cross section of a zeolite-heparin polymer-simulated blended microsphere with Na-LTA zeolite powder added; FIG. 2 is a graph showing the adsorption amount of potassium ions and the fluctuation amount of sodium ion concentration by the microspheres in each example;

FIG. 3 is a graph showing the amount of bovine serum albumin adsorbed by the microspheres in each example;

FIG. 4 shows the hemolysis ratio of the microsphere pair in each example.

Detailed Description

The present invention will be further illustrated with reference to the following examples. It should be noted that: the parts in the present invention mean parts by weight unless otherwise specified.

The performance test method of the microsphere prepared by the invention comprises the following steps:

the potassium ion adsorption test for the microspheres was obtained from a static adsorption test. 50mg of the freeze-dried microspheres were weighed and soaked in physiological saline in a plastic centrifuge tube for pretreatment for 2 hours. Physiological saline was aspirated, and 20mL of potassium-enriched serum was added to the wet microspheres obtained above, followed by shaking in an incubator at 37 ℃ for 3 hours. The potassium ion concentration before and after adsorption was measured using an automatic biochemical analyzer. The adsorption amount is calculated by the following formula:

unit potassium ion adsorption amount (initial blood potassium concentration-post-adsorption blood potassium concentration)/mass of lyophilized microspheres/volume of adsorbed serum

For the test of the anti-protein adhesion performance of the microspheres, the static adsorption test of bovine serum albumin is taken as an example. 10mg of the microsphere sample was immersed in a phosphate buffer solution of bovine serum albumin at a concentration of 1mg/mL and treated at 37 ℃ for 1 hour. The microspheres are washed by phosphate buffer solution and deionized water in sequence, placed in washing solution containing 2% of dialkyl sodium sulfate and 0.05mol/L of sodium hydroxide, and vibrated at 37 ℃ for 2h to desorb adsorbed protein. The protein concentration in the washing solution was measured using a Micro BCA protein assay kit (Thermo Scientific, Pierce) to calculate the amount of protein adsorbed.

For the blood compatibility test of the microspheres, the hemolysis rate test is taken as an example. 5mg microsphere samples were pre-treated by soaking in phosphate buffer for 12 hours and incubated at 37 ℃ for 1 hour. Mixing phosphate buffer solution with whole blood according to the volume ratio of 1: 1, and separating the mixture for 15 minutes using a centrifuge at a centrifugation rate of 2000rpm to obtain erythrocytes. The procedure for separating red blood cells was repeated 5 times. 0.2mL of erythrocytes and 0.8mL of phosphate buffer were added to the above pretreated microsphere sample and shaken in an incubator at 37 ℃ for 2 hours. The suspension was centrifuged using a centrifuge at 8000rpm for 5 minutes. The suspension was tested for absorbance using an ultraviolet-visible spectrometer. Deionized water and phosphate buffer were set as positive and negative controls, respectively. The hemolysis rate is calculated as follows:

the hemolysis ratio (%) × (suspension absorbance-absorbance of negative control)/(absorbance of positive control-absorbance of negative control) × 100%.

Example 1.

This example aims to illustrate a more ideal formula and process of a zeolite-heparin polymer-simulated blended microsphere with Na-LTA zeolite powder:

75 parts of a polyether sulfone solution (8 parts of polyether sulfone, 92 parts of dimethylformamide) was added to 3 parts of a polymerization reaction stock solution (65 parts of acrylic acid, 22 parts of N-vinylpyrrolidone, 4 parts of azobisisobutyronitrile, 8 parts of N, N' -methylenebisacrylamide), and the mixture was stirred and heated at 120 ℃ for 36 hours. Adding 22 parts of Na-LTA type zeolite powder, stirring for 4 hours at room temperature, ultrasonically dispersing for 3 hours, and defoaming for 1 hour under negative pressure to obtain zeolite-heparin simulated polymer suspension; the mixture is filled into an injector, and is subjected to electrospray under an 8kV electrostatic field to form liquid drops smoothly, so that the injection is easy; the suspension is uniform and stable, and is not easy to delaminate; phase separation rapidly occurs in a mixed coagulation bath of ethanol and water (1:3) to form microspheres of uniform size. The scanning electron microscope image of the microspheres after freeze drying and half cutting is shown in figure 1, and as can be seen from figure 1, the microspheres have good appearance and the internal structure has porous characteristics. And the water contact angle of the microsphere is measured to be 0, and the microsphere shows good hydrophilicity.

The results of the potassium ion adsorption capacity, the anti-protein adhesion property and the hemolysis rate performed according to the above-described method are shown in FIGS. 2, 3 and 4, and it can be seen from these figures that the microspheres of this example have a better potassium ion adsorption capacity, an anti-protein adhesion property and a lower hemolysis rate.

Example 2.

This example is intended to illustrate the effect of heparin-mimetic polymer synthesized by polymerization on blended microspheres and differs from example 1 by the addition of the minimum amount of polymerization stock:

78 parts of a polyether sulfone solution (8 parts of polyether sulfone, 92 parts of dimethylformamide) was added to 1 part of a polymerization reaction stock solution (65 parts of acrylic acid, 22 parts of N-vinylpyrrolidone, 4 parts of azobisisobutyronitrile, 8 parts of N, N' -methylenebisacrylamide), and the mixture was stirred and heated at 120 ℃ for 36 hours. 22 parts of Na-LTA type zeolite powder is added, stirred for 4 hours at room temperature, ultrasonically dispersed for 3 hours, and defoamed for 1 hour under negative pressure to obtain the zeolite-heparin analogue polymer suspension. The mixture is filled into an injector, and liquid drops are smoothly formed by electrospray in an 8kV electrostatic field, so that the injection is easy; the suspension stability is better, but is reduced compared with that of the example 1; the microspheres are rapidly separated in a mixed coagulating bath (1:3) of ethanol and water to form microspheres with uniform size and good appearance.

In terms of performance, it can be seen from the figure that the microspheres prepared in the embodiment have better potassium ion adsorption capacity, the anti-protein adhesion performance is reduced compared with that of the embodiment 1, and the hemolysis rate is reduced compared with that of the embodiment 1.

Example 3.

This example is intended to illustrate the effect of heparin-mimetic polymer synthesized by polymerization on blended microspheres, and differs from example 1 in that the maximum amount of polymerization stock solution was added:

78 parts of a polyether sulfone solution (8 parts of polyether sulfone, 92 parts of dimethylformamide) was added to 5 parts of a polymerization reaction stock solution (65 parts of acrylic acid, 22 parts of N-vinylpyrrolidone, 4 parts of azobisisobutyronitrile, 8 parts of N, N' -methylenebisacrylamide), and the mixture was stirred and heated at 120 ℃ for 36 hours. 22 parts of Na-LTA type zeolite powder is added, stirred for 4 hours at room temperature, ultrasonically dispersed for 3 hours, and defoamed for 1 hour under negative pressure to obtain the zeolite-heparin analogue polymer suspension. The mixture is filled into an injector, and liquid drops are smoothly formed by electrospray in an 8kV electrostatic field, so that the injection is easy; the suspension has good stability; the microspheres are rapidly separated in a mixed coagulating bath (1:3) of ethanol and water to form microspheres with uniform size and good appearance.

In terms of performance, it can be seen from the figure that the microspheres prepared in the embodiment have better potassium ion adsorption capacity, the protein adhesion resistance is improved compared with that of the embodiment 1, but the hemolysis rate is increased compared with that of the embodiment 1.

Example 4.

This example is intended to illustrate the effect of temperature and time on the blended microspheres by polymerization, differing from example 1 by reducing the temperature and time of polymerization:

75 parts of a polyether sulfone solution (8 parts of polyether sulfone, 92 parts of dimethylformamide) was added to 3 parts of a polymerization reaction stock solution (65 parts of acrylic acid, 22 parts of N-vinylpyrrolidone, 4 parts of azobisisobutyronitrile, 8 parts of N, N' -methylenebisacrylamide), and the mixture was stirred and heated at 90 ℃ for 12 hours. 22 parts of Na-LTA type zeolite powder is added, stirred for 4 hours at room temperature, ultrasonically dispersed for 3 hours, and defoamed for 1 hour under negative pressure to obtain the zeolite-heparin analogue polymer suspension. The mixture is filled into an injector, and is subjected to electrospray under an 8kV electrostatic field to form liquid drops smoothly, so that the injection is easy; the suspension is uniform and stable, and is not easy to delaminate; rapidly phase-separating in a mixed coagulating bath (1:3) of ethanol and water to form microspheres with uniform size; however, the coagulation bath appeared cloudy due to the dissolution of insufficiently reacted hydrophilic oligomers and the accompanying escape of zeolite particles. As a result, the microsphere has a good appearance.

In terms of performance, it can be seen from the figure that the potassium ion adsorption capacity and the protein adhesion resistance of the microspheres are reduced compared with example 1, and the hemolysis rate is reduced compared with example 1.

Example 5.

This example is intended to illustrate the effect of the ultrasonic and negative pressure defoaming treatments after adding zeolite particles and stirring on the blended microspheres, and differs from example 1 in that ultrasonic and negative pressure defoaming are not performed:

75 parts of a polyether sulfone solution (8 parts of polyether sulfone, 92 parts of dimethylformamide) was added to 3 parts of a polymerization reaction stock solution (65 parts of acrylic acid, 22 parts of N-vinylpyrrolidone, 4 parts of azobisisobutyronitrile, 8 parts of N, N' -methylenebisacrylamide), and the mixture was stirred and heated at 120 ℃ for 36 hours. 22 parts of Na-LTA type zeolite powder is added, stirred for 4 hours at room temperature without ultrasonic treatment and negative pressure defoaming, and the zeolite-heparin analogue polymer suspension is obtained. The mixture is filled into an injector, and the electric spray is carried out under an 8kV electrostatic field to form liquid drops smoothly, so that the injection difficulty is increased compared with that of the embodiment 1; the suspension is uniform and stable, but is easy to delaminate compared with the suspension in example 1; phase separation rapidly occurs in a mixed coagulation bath of ethanol and water (1:3) to form microspheres of uniform size.

In terms of performance, it can be seen from the figure that the potassium ion adsorption capacity, the protein adhesion resistance and the hemolysis rate of the microspheres are close to those of example 1.

Example 6.

This example is intended to illustrate the effect of the type of zeolite particles added on the blended microspheres, and differs from example 1 by using a MOR type zeolite powder with a higher elemental silicon content:

75 parts of a polyether sulfone solution (8 parts of polyether sulfone, 92 parts of dimethylformamide) was added to 3 parts of a polymerization reaction stock solution (65 parts of acrylic acid, 22 parts of N-vinylpyrrolidone, 4 parts of azobisisobutyronitrile, 8 parts of N, N' -methylenebisacrylamide), and the mixture was stirred and heated at 120 ℃ for 36 hours. 22 parts of MOR type zeolite powder having a higher silicon content than that of Na-LTA type zeolite in example 1 was added, stirred at room temperature for 4 hours, ultrasonically dispersed for 3 hours, and defoamed under negative pressure for 1 hour to obtain a zeolite-heparin-mimetic polymer suspension. The mixture is filled into an injector, and the liquid drops formed by electrospray under an 8kV electrostatic field are not smooth and difficult to inject; the suspension is not stable enough and is easy to delaminate; in the mixed coagulation bath (1:3) of ethanol and water, a large amount of white powder was diffused into the coagulation bath while phase separation was caused, and microspheres having a uniform size were formed.

In terms of performance, as can be seen from the figure, the potassium ion adsorption capacity and the blood compatibility of the microspheres are obviously reduced compared with example 1, the anti-protein adhesion performance is obviously reduced compared with example 1, and the hemolysis rate is obviously improved compared with example 1.

The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.

Claims

1. A zeolite-heparin mimic polymer blending microsphere is characterized in that: the composition comprises the following components in parts by weight:

1) polyether sulfone solution:

6-12 parts of polyether sulfone

88-94 parts of organic solvent

2) Zeolite powder;

the zeolite powder is LTA type, LAU type or HEU type;

3) polymerization reaction stock solution:

55-75 parts of acrylic acid

10-30 parts of N-vinyl pyrrolidone

2-10 parts of oil-soluble azo initiator

2-15 parts of amide group-containing crosslinking agent

The weight ratio of the polyether sulfone solution to the zeolite powder to the polymerization reaction stock solution is (65-85): (12-32): (1-5);

the preparation method comprises the following steps:

1) preparation of polyether sulfone solution

2) preparation of heparin analogue polymer solution

3) formulation of Zeolite-heparin mimetic Polymer suspensions

2. The zeolite-heparin mimetic polymer blended microsphere of claim 1, wherein: the organic solvent is at least one of dimethylformamide, dimethylacetamide or dimethyl sulfoxide.

3. The zeolite-heparin mimetic polymer blended microsphere of claim 1, wherein: the oil-soluble azo initiator is azobisisobutyronitrile.

4. The zeolite-heparin mimetic polymer blended microsphere of claim 1, wherein: the amide group-containing cross-linking agent is N, N' -methylenebisacrylamide.

5. The zeolite-heparin mimetic polymer blended microsphere of claim 1, wherein: in the step 4), the electrostatic field is formed through an electrostatic spinning machine.

6. The zeolite-heparin mimetic polymer blended microsphere of claim 1, wherein: in the step 4), the diameter of the microsphere is controlled to be 200-2000 μm by adjusting the electrostatic voltage, the aperture of the syringe needle or the injection speed.

7. Use of the zeolite-heparin-mimicking polymer blend microspheres of any one of claims 1-6 for the preparation of a blood purification device.

8. Use according to claim 7, characterized in that: the blood purification is hyperkalemia blood purification.