High-elasticity low-expansion polyacrylic resin microsphere and preparation method thereof

Abstract

The invention provides a high-elasticity low-expansion polyacrylic resin microsphere and a preparation method thereof, and belongs to the technical field of microsphere preparation. The acrylic acid is used as a raw material base material, the functional soft monomer is added, the types and contents of the initiator, the cross-linking agent, the surfactant and the oil phase are adaptively limited, and meanwhile, a specific cross-linking environment and the like are selected, so that the performance of the final product polyacrylic acid microspheres is improved, on one hand,-COOH groups in the acrylic acid are reserved, and on the other hand, the performance of the polyacrylic acid microspheres is improved; the prepared microspheres contain-COOH groups and can be used for loading positive charge chemotherapeutic drugs; on the other hand, due to the addition of the functional soft monomer, the elasticity of the microspheres is improved, the hydrophilicity of the microspheres is reduced, and the microspheres are not prone to expansion in a solution, so that it is guaranteed that the size change of the microspheres is small during interventional therapy, precise embolism is achieved, and the usability of the microsphere product is improved.

Description

Technical Field

[0001] The present invention relates to a polyacrylic acid resin microsphere and a preparation method thereof, in particular to a polyacrylic acid resin microsphere with high elasticity and low expansion degree and a preparation method thereof, belonging to the technical field of microsphere preparation. Background Art

[0002] Microsphere materials are core basic materials indispensable in many fields such as biomedicine, analytical detection, and in vitro diagnosis. In interventional therapy, as an important embolization agent, microspheres have advantages such as precise embolization and targeted slow release. As a new material with broad application prospects, polyacrylic acid resin microspheres have characteristics such as good biocompatibility, good stability, and tunability when used to prepare biomedical materials.

[0003] Regarding the preparation methods of polyacrylic acid resin microspheres, there have been many patent literatures reported. For example, in CN112391021A "A preparation method of a modified soft polyacrylic acid resin microsphere", a hard nano-scale polymethyl methacrylate microsphere dispersion liquid is prepared by an emulsion polymerization process, and then an acrylic monomer solution containing an initiator is added to the dispersion liquid, and the reaction conditions are controlled to perform acrylic graft modification on the polymethyl methacrylate microspheres, thereby obtaining the modified soft polyacrylic acid resin microspheres. In CN103554331A "A method for preparing polyacrylic acid superabsorbent resin microspheres by inverse suspension polymerization", polyacrylic acid superabsorbent resin microspheres with high water absorption are prepared by inverse suspension polymerization. The obtained microspheres have high water absorption (for example, in Example 1: the resin is microspherical, the particle size is 0.23 microns, the absorption of deionized water is 950 g / g, and the absorption of 0.9% NaCl brine is 84 g / g), and one-step large-batch continuous preparation of polyacrylic acid superabsorbent resin microspheres can be realized. Also, in "The Preparation and Evaluation of Blank and Doxorubicin-Loaded Polyacrylic Acid Embolic Microspheres, Journal of Peking University", the preparation method and property evaluation of ion-exchange type doxorubicin-loaded polyacrylic acid embolization microspheres are studied. The prepared microspheres all have good compression resistance and good doxorubicin loading performance, and are a potential new drug delivery system that can be used for arterial chemoembolization.

[0004] Furthermore, it can be concluded that for the preparation of polyacrylic acid resin microspheres, methods such as homogeneous emulsification method and suspension polymerization method are mostly used, but these microspheres have uneven and uncontrollable particle sizes, are prone to swelling in the aqueous phase, resulting in a large increase in the particle size of the microspheres, and it is difficult to completely recover to the original size after being compressed, which greatly limits the application of polyacrylic acid resin microspheres in the biomedical field. Especially when used as an ideal embolization material, it should have good elasticity to ensure smooth passage through the interventional catheter, and after being pushed out of the catheter, it can return to its original shape to improve the safety of embolization treatment. Summary of the Invention

[0005] The present invention aims to solve the problems in the prior art that polyacrylic resin microspheres have poor deformability and are not easily restored to their original spherical shape after pressing; polyacrylic resin microspheres have high water absorbency and swell greatly in water; and, when preparing polyacrylic resin microspheres, mainly homogeneous emulsification method, suspension polymerization method, etc. are used, and the prepared microspheres have uneven sizes. A polyacrylic resin microsphere with high elasticity and low expansion degree and its preparation method are proposed.

[0006] In order to achieve the above technical objectives, the following technical solutions are proposed: The first objective of this technical solution is to provide: a polyacrylic resin microsphere with high elasticity and low expansion degree, which is prepared by mixing acrylic acid, a functional soft monomer, an initiator and a crosslinking agent in water to obtain a dispersed phase solution; dissolving a surfactant in an oil phase to obtain a continuous phase solution; and then, through the microfluidic method. Among them, in the dispersed phase solution, the mass-volume percentage concentration of acrylic acid is 50 - 500% g / mL, the mass-volume percentage concentration of the functional soft monomer is 10 - 100% g / mL, the mass-volume percentage concentration of the initiator is 0.1 - 5% g / mL, and the mass-volume percentage concentration of the crosslinking agent is 0.01 - 3% g / mL. When the amount of acrylic acid is certain, the initiator such as potassium persulfate or ammonium persulfate and the crosslinking agent affect each other. If the amount of this initiator is large, the crosslinking agent will precipitate, and as the content of acrylic acid increases, the solubility of these two substances, the initiator and the crosslinking agent, decreases; while the water-soluble azo initiator and the crosslinking agent have less influence on each other. In addition, if the addition amount of the functional soft monomer is too much, stratification will occur; and, if the addition amount of acrylic acid increases, correspondingly, the addition amount of the functional soft monomer increases; conversely, if the addition amount of acrylic acid decreases, correspondingly, the addition amount of the functional soft monomer decreases; based on this, in order to ensure the high-elasticity and low-expansion-degree performance of the polyacrylic resin microspheres on the one hand, and to ensure the stability and scale of the preparation process of the polyacrylic resin microspheres on the other hand, the mass-volume percentage concentrations of acrylic acid, the functional soft monomer, the initiator and the crosslinking agent in the dispersed phase solution are specifically defined.

[0007] The product performance indicators of the polyacrylic resin microsphere with high elasticity and low expansion degree include: compressibility ≤ 20%, recovery ≥ 90%, expansion degree ≤ 20% and CV ≤ 10%.

[0008] The second objective of this technical solution is to provide: a preparation method of a polyacrylic resin microsphere with high elasticity and low expansion degree, which includes the following steps: S1: Dissolve acrylic acid, a functional soft monomer, an initiator and a crosslinking agent in water, and mix evenly to obtain a dispersed phase solution. S2: Dissolve the surfactant in the oil phase to obtain a continuous phase solution. S3: Pass the dispersed phase solution obtained in step S1 and the continuous phase solution obtained in step S2 through a microfluidic device to form acrylic-based mixed liquid droplets; then, send the acrylic-based mixed liquid droplets into an oil phase at 50-110 °C for crosslinking; remove the upper oil phase and filter to facilitate subsequent thorough cleaning, obtaining a crude microsphere product. S4: Wash and dry the crude microsphere product obtained in step S3 to obtain polyacrylic resin microspheres with high elasticity and low expansion degree.

[0009] Preferably, the functional soft monomer is one or any mixture of two or more of ethyl acrylate, butyl acrylate, isooctyl acrylate, lauryl acrylate, butyl methacrylate, n-octyl methacrylate, isooctyl methacrylate, and lauryl methacrylate.

[0010] Preferably, the oil phase is vegetable oil or mineral oil. Among them, the vegetable oil is one or any mixture of two or more of soybean oil, peanut oil, rapeseed oil, and sesame oil, and the mineral oil is liquid paraffin.

[0011] Preferably, when the oil phase is vegetable oil, the surfactant in step S2 is one or any mixture of two or more of Span80, Span85, Tween80, and PGPR, and the surfactant concentration is 1-10%wt; when the oil phase is mineral oil, the surfactant in step S2 is alkylphenol polyoxyethylene ether or / and polyisobutylene succinimide, and the surfactant concentration is 1-10%wt.

[0012] Preferably, the initiator is one or any mixture of two or more of ammonium persulfate, potassium persulfate, and water-soluble azo initiators.

[0013] Preferably, the crosslinking agent is N, N-methylenebisacrylamide or / and polyethylene glycol diacrylate.

[0014] Preferably, step S4 uses a multi-stage cleaning method to wash the crude microsphere product; in the multi-stage cleaning process, a cleaning agent, ethanol, and deionized water are used in sequence.

[0015] Preferably, when the oil phase is vegetable oil, in the corresponding step S4, the cleaning agent is one or any mixture of two or more of isopropanol, n-octanol, acetone, and ethyl acetate; when the oil phase is mineral oil, in the corresponding step S4, the cleaning agent is one or any mixture of two or more of petroleum ether, ether, and chloroform.

[0016] In this technical solution, the explanation of "mass - volume percentage concentration" is: mass / volume * 100%. For example, 50% g / mL means 1 g / 2 mL * 100%. "Functional soft monomer" refers to a monomer that can provide specific functional groups and has a relatively low glass transition temperature of its homopolymer. Specifically, it includes ethyl acrylate, butyl acrylate, isooctyl acrylate, lauryl acrylate, butyl methacrylate, n - octyl methacrylate, isooctyl methacrylate, lauryl methacrylate, etc.

[0017] In this technical solution, the involved mechanisms include: The glass transition temperature of the raw material acrylic acid homopolymer is relatively high. In this technical solution, due to the fact that the functional soft monomer has a relatively low glass transition temperature of its homopolymer, when it polymerizes with acrylic acid, it can effectively improve the elasticity of the polyacrylic acid resin microspheres, endowing the polyacrylic acid resin microspheres with a certain degree of flexibility and extensibility. In addition, the functional soft monomer has a certain degree of hydrophobicity. After it polymerizes with acrylic acid, it can effectively reduce the water absorption and swelling performance of the polyacrylic acid resin microspheres, thereby reducing the degree of swelling of the polyacrylic acid resin microspheres. While the polyacrylic acid resin microspheres prepared only with acrylic acid in the prior art have poor elasticity, etc.

[0018] Adopting this technical solution brings the following beneficial technical effects: First, in the present invention, using acrylic acid as the raw material substrate, through the addition of functional soft monomers, and by appropriately limiting the types and contents of initiators, cross - linkers, surfactants, and oil phases, and at the same time, selecting a specific cross - linking environment, etc., the performance of the final product polyacrylic acid microspheres is improved. On the one hand, the - COOH groups in acrylic acid are retained, so that the prepared microspheres contain - COOH groups and can be used to load positively charged chemotherapeutic drugs. On the other hand, the addition of functional soft monomers improves the elasticity of the microspheres and reduces their hydrophilicity, making the microspheres not easily swell in solution, thus ensuring that the size of the microspheres changes little during interventional treatment, achieving precise embolization, that is, improving the usability of this microsphere product. Second, in the present invention, the prepared polyacrylic acid resin microspheres have high elasticity and high recoverability (low degree of swelling), which is conducive to passing through the interventional catheter and fully recovering at the embolization site, effectively avoiding the risks of intraoperative ectopic embolization and incomplete embolization. Third, in the present invention, the polyacrylic acid resin microspheres prepared by using a microfluidic device have good monodispersity, uniform shape, and controllable particle size. Description of the Drawings

[0019] Figure 1 Schematic diagram of the elastic measurement process of the polyacrylic acid resin microsphere product in Example 3 (A: before compression); Figure 2 Schematic diagram of the elastic measurement process of the polyacrylic acid resin microsphere product in Example 3 (B: during compression); Figure 3 Schematic diagram of the elastic measurement process of the polyacrylic acid resin microsphere product in Example 3 (C: after compression); Figure 4 Schematic diagram of the polyacrylic acid resin microsphere product before expansion in Example 3 (A); Figure 5 Schematic diagram of the polyacrylic acid resin microsphere product after expansion in Example 3 (B); Figure 6 The polyacrylic acid resin microspheres in Example 3 have a drug-loading effect on gemcitabine; Figure 7 Schematic diagram of the polyacrylic acid resin microsphere product before expansion in Example 4 when the initiator is potassium persulfate or ammonium persulfate and the initiator concentration is 0.1% g / mL (a); Figure 8 Schematic diagram of the polyacrylic acid resin microsphere product after expansion in Example 4 when the initiator is potassium persulfate or ammonium persulfate and the initiator concentration is 0.1% g / mL (b); Figure 9 Schematic diagram of the polyacrylic acid resin microsphere product before expansion in Example 4 when the initiator is potassium persulfate or ammonium persulfate and the initiator concentration is 1.5% g / mL (c); Figure 10 Schematic diagram of the polyacrylic acid resin microsphere product after expansion in Example 4 when the initiator is potassium persulfate or ammonium persulfate and the initiator concentration is 1.5% g / mL (d); Figure 11 Schematic diagram of the polyacrylic acid resin microsphere product before expansion in Example 4 when the initiator is potassium persulfate or ammonium persulfate and the initiator concentration is 3% g / mL (e); Figure 12 Schematic diagram of the polyacrylic acid resin microsphere product after expansion in Example 4 when the initiator is potassium persulfate or ammonium persulfate and the initiator concentration is 3% g / mL (f); Figure 13 Schematic diagram of the polyacrylic acid resin microsphere product before expansion in Example 4 when the initiator is a water-soluble azo initiator and the initiator concentration is 0.1% g / mL (a); Figure 14 Schematic diagram of the polyacrylic acid resin microsphere product after expansion in Example 4 when the initiator is a water-soluble azo initiator and the initiator concentration is 0.1% g / mL (b); Figure 15Schematic diagram (c) of the polyacrylic acid resin microsphere product before swelling when the initiator in Example 4 is a water-soluble azo initiator and the initiator concentration is 5% g / mL; Figure 16 Schematic diagram (d) of the polyacrylic acid resin microsphere product after swelling when the initiator in Example 4 is a water-soluble azo initiator and the initiator concentration is 5% g / mL. Detailed implementation manners

[0020] The technical solutions in the embodiments of the present invention are clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts belong to the scope of protection of the present invention.

[0021] In the following embodiments, the materials involved, acrylic acid, potassium persulfate or / water-soluble azo initiator, ethyl acrylate, and N,N-methylenebisacrylamide are all purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.

[0022] Example 1 This example provides a method for preparing polyacrylic acid resin microspheres with high elasticity and low expansion degree, including the following steps: (1) Preparation of the dispersed phase solution Dissolve acrylic acid, ethyl acrylate, potassium persulfate, and N,N-methylenebisacrylamide in water and mix evenly to obtain a dispersed phase solution; wherein, the mass-volume percentage concentration of acrylic acid is 50% g / mL, the mass-volume percentage concentration of ethyl acrylate is 50% g / mL, the mass-volume percentage concentration of potassium persulfate is 0.1% g / mL, and the mass-volume percentage concentration of N,N-methylenebisacrylamide is 0.01% g / mL; (2) Preparation of the continuous phase solution Dissolve the surfactant PGPR in soybean oil to obtain a continuous phase solution; wherein, the concentration of the surfactant PGRP is 5%wt; (3) Microfluidic method Using a microfluidic device, make the dispersed phase solution and the continuous phase solution into acrylic-based mixed liquid droplets, introduce the acrylic-based mixed liquid droplets into the oil phase at 105°C for crosslinking; after crosslinking is completed, remove the upper oil phase solution to obtain a microsphere crude product; wherein, the oil phase is soybean oil; (4) Wash the microsphere crude product successively with isopropyl alcohol, ethanol, and deionized water, and then dry to obtain a polyacrylic acid resin microsphere product with high elasticity and low expansion degree.

[0023] Example 2 This embodiment provides a method for preparing polyacrylic resin microspheres with high elasticity and low expansion degree, comprising the following steps: (1) Preparation of the dispersed phase solution Dissolve acrylic acid, butyl methacrylate, potassium persulfate, and N, N - methylenebisacrylamide in water, and mix evenly to obtain the dispersed phase solution; wherein, the mass - volume percentage concentration of acrylic acid is 400% g / mL, the mass - volume percentage concentration of butyl methacrylate is 100% g / mL, the mass - volume percentage concentration of potassium persulfate is 0.1% g / mL, and the mass - volume percentage concentration of N, N - methylenebisacrylamide is 0.01% g / mL; (2) Preparation of the continuous phase solution Dissolve the surfactant polyisobutenyl succinimide in liquid paraffin to obtain the continuous phase solution; wherein, the concentration of the surfactant polyisobutenyl succinimide is 5% wt; (3) Microfluidic method Using a microfluidic device, make the dispersed phase solution and the continuous phase solution into acrylic - based mixed liquid droplets, introduce the acrylic - based mixed liquid droplets into the oil phase at 105 °C for cross - linking; after cross - linking is completed, remove the upper - layer oil - phase solution to obtain the initial microspheres; wherein, the oil phase is liquid paraffin; (4) Wash the initial microspheres successively with petroleum ether, ethanol, and deionized water, and then dry to obtain the polyacrylic resin microsphere product with high elasticity and low expansion degree.

[0024] Example 3 On the basis of Example 2, this example conducts performance tests on the polyacrylic resin microsphere product obtained in Example 2, specifically as follows: I. Mechanical property test Use a microscopic mechanical property operating instrument (model: MF - WSF1) to conduct a compression experiment on a single microsphere, and measure each microsphere in parallel three times; The physical property analyzer is equipped with a flat - bottom cylindrical glass pressing needle with a diameter of 1 mm, an optical microscope, and a 5 N force sensor; Before the experiment, first measure the microsphere particle size R0; then, control the speed to compress the microsphere until the force detected by the force sensor reaches 100 N, and measure the longitudinal diameter R of the compressed microsphere c ; after the measurement is completed, remove the flat - bottom cylindrical glass pressing needle, and when the microsphere returns to its original shape, measure the particle size R of the microsphere that has returned to its original shape e ; During the experiment, the force sensor collects 100 data points per second, and collects microsphere compression photos through an optical microscope. Then, analyze the test data through a computer, and calculate the compressibility and recoverability of the microspheres through the following formula: Compressibility=(1-(R0 - R c) / R0)×100%; Recovery = (1 - (R0 - R e ) / R0)×100%; The results are as Figures 1-3 shown. During this process, the size changes of the polyacrylic acid resin microspheres are as shown in Table 1 below: From the above experiments, it can be seen that the polyacrylic acid resin microspheres have high elasticity, that is, the compressibility ≤ 20% and the recovery ≥ 90%.

[0025] II. Swelling property test The swelling degree test method of the polyacrylic acid resin microspheres is as follows: 1. Uniformly distribute the microspheres before swelling on a glass slide, and then observe and take pictures under an optical microscope; 2. Measure and count the particle sizes of the microspheres in the pictures taken in step 1 to obtain the average particle size R0 of the microspheres before swelling; 3. Collect the microspheres in a vial, add sufficient deionized water, take out the microspheres after 24 h, and observe and take pictures under an optical microscope; 4. Measure and count the particle sizes of the microspheres in the pictures taken in step 3 to obtain the average particle size R1 of the microspheres before swelling; 5. Calculate the swelling degree of the polyacrylic acid resin microspheres according to the following formula: Swelling degree = (R1 - R0) / R0 × 100% The results are as Figures 4-5 shown. The size changes of the polyacrylic acid resin microspheres are as shown in Table 2 below; Therefore, it can be known that the polyacrylic acid resin microspheres have poor swelling performance in solution and have a low swelling degree (≤ 20%).

[0026] III. Drug loading performance Use the polyacrylic acid resin microsphere product obtained in Example 2 to load gemcitabine (10 mg / ml) to test the drug loading performance of the polyacrylic acid resin microsphere product.

[0027] 1) Prepare a standard solution: Take 200 mg of gemcitabine and prepare a standard solution with an initial concentration of 10 mg / ml in 20 mL; 2) Take 5 mL of this standard solution and add it to three vials (three parallel samples, each vial contains 25 mg of polyacrylic acid resin microspheres); 3) Establish a standard curve: Take 0.075 mL, 0.1 mL, 0.15 mL, 0.2 mL, and 0.25 mL respectively, dilute to 100 mL to a constant volume, then detect the absorbance of the solution with an ultraviolet spectrophotometer (wavelength 268 nm), and establish a standard curve of drug concentration based on the absorbance values; 4) At 0 min, 5 min, 10 min, 15 min, and 30 min respectively, take 0.1 mL of the supernatant and dilute it to 50 mL to a constant volume, then detect the absorbance of the solution with an ultraviolet spectrophotometer (wavelength 268 nm); 5) Calculate the drug concentration (Ce) in the supernatant according to the absorbance value; 6) Calculate the drug loading amount (mg / mg) of the microspheres according to the following formula and draw a drug loading curve: Drug loading amount = (10 - Ce) * 5 / 25) × 100% From Figure 6 it can be seen that the polyacrylic acid resin microspheres have a drug loading effect on gemcitabine, and the drug loading amount of gemcitabine reaches 0.32 mg / mg at 30 min.

[0028] Example 4 In the present invention, the influence of different initiator types and initiator concentrations on the performance of polyacrylic acid resin microspheres is discussed. Among them, the functional soft monomer is butyl methacrylate, and the crosslinking agent is N, N - methylenebisacrylamide. The preparation of polyacrylic acid resin microspheres includes the following steps: (1) Preparation of the dispersed phase solution Dissolve acrylic acid, butyl methacrylate, initiator, and N, N - methylenebisacrylamide in water, mix evenly to obtain a dispersed phase solution; among them, the mass - volume percentage concentration of acrylic acid is 50% g / mL, the mass - volume percentage concentration of butyl methacrylate is 10% g / mL, the mass - volume percentage concentration of the initiator is a% g / mL, and the mass - volume percentage concentration of N, N - methylenebisacrylamide is 3% g / mL; (2) Preparation of the continuous phase solution Dissolve the surfactant PGPR in soybean oil to obtain a continuous phase solution; among them, the concentration of the surfactant PGRP is 5%wt; (3) Microfluidic method Using a microfluidic device, make the dispersed phase solution and the continuous phase solution into acrylic - based mixed liquid droplets, introduce the acrylic - based mixed liquid droplets into an oil phase at 105 °C for cross - linking; after cross - linking is completed, remove the upper - layer oil - phase solution to obtain the microsphere crude product; among them, the oil phase is soybean oil; (4) Wash the microsphere crude product successively with isopropanol, ethanol, and deionized water, and then dry to obtain the polyacrylic acid resin microsphere product; The obtained results are shown in Table 3 below; Furthermore, it can be known that the initiator type is potassium persulfate or ammonium persulfate. When the concentration of this initiator is low, the initiation efficiency is low, and the cross-linking degree of the microspheres is low. Therefore, its swelling performance is good, and thus it has a high swelling degree; when the concentration of this initiator is high, the microspheres cross-link quickly and the cross-linking degree is good. Therefore, it has a low swelling degree. When the initiator type is a water-soluble azo initiator, due to the high initiation efficiency of the water-soluble azo initiator, a low concentration of this initiator can make the microspheres have a good cross-linking degree, and thus have a low swelling degree; when the concentration of the water-soluble azo initiator is too high, the acrylic acid solution cross-links rapidly, resulting in an increase in the viscosity of the acrylic acid solution, so that the acrylic acid droplets cannot be sheared out normally and spheres cannot be formed. Therefore, on the premise of ensuring the cross-linking rate and controlling the swelling degree, finally, the mass-volume percentage concentration of the initiator is limited to 0.1 - 5% g / mL.

[0029] The above are only the preferred embodiments of the present invention, and do not impose any form of limitation on the present invention. Any simple modification or equivalent change made to the above embodiments based on the technical essence of the present invention shall fall within the protection scope of the present invention.

Claims

1. A polyacrylic resin microsphere with high elasticity and low expansion degree, characterized in that, Acrylic acid, a functional soft monomer, an initiator, and a crosslinking agent are mixed and dissolved in water to obtain a dispersed phase solution; a surfactant is dissolved in an oil phase to obtain a continuous phase solution; then, it is prepared by a microfluidic method. Among them, in the dispersed phase solution, the mass-volume percentage concentration of acrylic acid is 50 - 500% g / mL, the mass-volume percentage concentration of the functional soft monomer is 10 - 100% g / mL, the mass-volume percentage concentration of the initiator is 0.1 - 5% g / mL, and the mass-volume percentage concentration of the crosslinking agent is 0.01 - 3% g / mL. The product performance indicators of the high-elastic and low-swelling polyacrylic acid resin microspheres include: compressibility ≤ 20%, recovery ≥ 90%, swelling degree ≤ 20%, and CV ≤ 10%.

2. A method for preparing polyacrylic resin microspheres with high elasticity and low expansion degree according to claim 1, characterized in that, It includes the following steps: S1: Dissolve acrylic acid, a functional soft monomer, an initiator, and a crosslinking agent in water, mix evenly to obtain a dispersed phase solution. S2: Dissolve the surfactant in the oil phase to obtain a continuous phase solution. S3: Pass the dispersed phase solution obtained in step S1 and the continuous phase solution obtained in step S2 through a microfluidic device to form acrylic acid-based mixed liquid droplets; then, send the acrylic acid-based mixed liquid droplets to an oil phase at 50 - 110 °C for crosslinking. Remove the upper oil phase, filter to facilitate subsequent thorough cleaning to obtain a crude microsphere product. S4: Wash and dry the crude microsphere product obtained in step S3 to obtain high-elastic and low-swelling polyacrylic acid resin microspheres.

3. The preparation method of the polyacrylic acid resin microspheres with high elasticity and low expansion degree according to claim 2, characterized in that, The functional soft monomer is one or any mixture of two or more of ethyl acrylate, butyl acrylate, isooctyl acrylate, lauryl acrylate, butyl methacrylate, n-octyl methacrylate, isooctyl methacrylate, and lauryl methacrylate.

4. The preparation method of the polyacrylic acid resin microspheres with high elasticity and low expansion degree according to claim 2, characterized in that, The oil phase is vegetable oil or mineral oil. Among them, the vegetable oil is soybean oil, peanut oil, rapeseed oil, or sesame oil, and the mineral oil is liquid paraffin.

5. The preparation method of the polyacrylic resin microspheres with high elasticity and low expansion degree according to claim 4, characterized in that, When the oil phase is vegetable oil, the surfactant in step S2 is one or any mixture of two or more of Span80, Span85, Tween80, and PGPR, and the surfactant concentration is 1 - 10% wt. When the oil phase is mineral oil, the surfactant in step S2 is alkylphenol polyoxyethylene ether or / and polyisobutylene succinimide, and the surfactant concentration is 1 - 10% wt.

6. The preparation method of the polyacrylic acid resin microspheres with high elastic expansion degree according to claim 2, wherein, The initiator is ammonium persulfate and / or potassium persulfate.

7. The preparation method of the polyacrylic resin microspheres with high elasticity and low expansion degree according to claim 2, wherein, The initiator is a water-soluble azo initiator.

8. The preparation method of the polyacrylic acid resin microspheres with high elasticity and low expansion degree according to claim 2, characterized in that, The crosslinking agent is N, N'-methylenebisacrylamide or / and polyethylene glycol diacrylate.

9. The preparation method of the polyacrylic acid resin microspheres with high elasticity and low expansion degree according to claim 2, wherein, Step S4 uses a multi-stage cleaning method to wash the crude microsphere product; in the multi-stage cleaning process, a cleaning agent, ethanol, and deionized water are used in sequence.

10. The preparation method of the polyacrylic acid resin microspheres with high elasticity and low expansion degree according to claim 4, characterized in that, When the oil phase is vegetable oil, the cleaning agent in step S4 is one or any mixture of two or more of isopropanol, n-octanol, acetone, and ethyl acetate. When the oil phase is mineral oil, the cleaning agent in step S4 is one or any mixture of two or more of petroleum ether, ether, and chloroform.

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