Core-shell type porous polymer microsphere, and preparation method therefor and use thereof

Abstract

Provided in the present application are a core-shell type porous polymer microsphere, and a preparation method therefor and the use thereof. In the preparation method for a core-shell type porous polymer microsphere provided by the present application, the particle size of the porous polymer microsphere and the respective thicknesses of a core layer and a shell layer can be regulated and controlled by selecting the particle size of a polymer seed, the amount of a first vinyl monomer and the amount of a second vinyl monomer; moreover, the pore size of the core layer of the microsphere can be controlled by controlling the amount ratio of a first pore-foaming agent to the first vinyl monomer, and the pore size of the shell layer of the microsphere can be controlled by controlling the amount ratio of a second pore-foaming agent to the second vinyl monomer; therefore, controllable preparation of the monodisperse core-shell type porous polymer microsphere is achieved, thereby obtaining the monodisperse core-shell type porous polymer microsphere having a highly uniform particle size that is adjustable within a wide range of 5-100 μm.

Description

Core-shell porous polymer microspheres and their preparation method and application

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to the Chinese patent application filed with the China Patent Office on January 26, 2024, with application number 202410110821.4 and application name “Core-shell type porous polymer microspheres and their preparation method and application”, all contents of which are incorporated by reference into this application. Technical Field

[0003] The present application relates to the technical field of polymer materials, and in particular to a core-shell porous polymer microsphere and a preparation method and application thereof. Background Art

[0004] Porous polymer microspheres have shown broad applications and significant advantages in the separation and purification of peptides, insulin, antibiotics, recombinant proteins, vaccines, and nucleotides due to their advantages such as good acid and alkali resistance, high mechanical strength, good separation and purification effects, and long service life. The pore structure and pore size of conventional porous polymer microspheres are similar from the surface to the inside. The uniform pore structure usually allows them to have a single property when used as a filler, such as molecular exclusion or specific binding properties. In recent years, new core-shell porous polymer microspheres have shown dual properties of molecular exclusion and specific binding when used as multimodal chromatographic fillers due to their special core-shell structure. They have the advantages of simplicity and high efficiency in the purification of multi-scale samples such as viruses and biomacromolecules. This type of core-shell porous polymer microspheres usually has a small-sized pore structure in the surface shell and a large-sized pore structure in the internal core. The non-uniform distribution of pore size from the outside to the inside also makes the controllable preparation of core-shell porous polymer microspheres a huge challenge.

[0005] In view of this, this application is hereby filed.

[0006] Summary of the Invention

[0007] The main purpose of the present application is to provide a core-shell porous polymer microsphere and a preparation method thereof, so as to solve the huge challenge problem in the prior art that the core-shell porous polymer microsphere has a non-uniformly distributed pore size from the outside to the inside so that it can be controlled.

[0008] To achieve the above-mentioned objectives, according to one aspect of the present application, a method for preparing core-shell porous polymer microspheres is provided, which comprises: step S1, mixing a first porogen, a first water, an optional first surfactant and an optional first cosolvent to obtain a first emulsion; mixing a first vinyl monomer, a first initiator, a second water and an optional second surfactant to obtain a second emulsion; mixing a second vinyl monomer, a second porogen, a second initiator, a third water and an optional third surfactant to obtain a third emulsion; step S2, mixing the first emulsion and a monodisperse polymer seed solution and performing a first swelling to obtain a first reaction liquid system; step S3, mixing the first reaction liquid system and the second emulsion and performing a second swelling to obtain a second reaction liquid system, and performing a first polymerization reaction on the second reaction liquid system to obtain a third reaction liquid system; step S4, mixing the third reaction liquid system and the third emulsion and performing a third swelling, and then performing a second polymerization reaction to obtain a fourth reaction liquid system; step S5, purifying the fourth reaction liquid system and removing the first porogen and the second porogen to obtain core-shell porous polymer microspheres.

[0009] Furthermore, the first porogen and the second porogen are each independently selected from at least one of dibutyl phthalate, toluene, cyclohexanol or 2-ethylhexanoic acid; and / or the first surfactant, the second surfactant and the third surfactant are each independently selected from at least one of sodium dodecyl sulfate, sodium dodecylbenzenesulfonate, polyvinyl pyrrolidone or polyvinyl alcohol; and / or the material of the polymer seed in the polymer seed solution is selected from at least one of polystyrene, polyacrylate, polystyrene acrylic latex particles or functionalized polystyrene; and / or the particle size of the polymer seed in the polymer seed solution is 0.5 to 20 μm; and / or, the first cosolvent is selected from at least one of acetone, butanol, 1-chlorodecane or chlorobenzene; and / or, the first vinyl monomer and the second vinyl monomer are each independently at least one of styrene, divinylbenzene, methyl methacrylate, glycidyl methacrylate or acrylonitrile; and / or, the first initiator and the second initiator are each independently at least one of a peroxide or an azo compound, the peroxide is selected from at least one of benzoyl peroxide, tert-butyl benzoyl peroxide or methyl ethyl ketone peroxide, and the azo compound is selected from at least one of azobisisobutyronitrile or azobisisoheptonitrile.

[0010] Furthermore, the mass ratio of the first porogen to the first vinyl monomer is 5 to 25:100; and / or the mass ratio of the second porogen to the second vinyl monomer is 50 to 200:100; and / or the mass ratio of the first vinyl monomer to the second vinyl monomer is 15 to 100:100.

[0011] Furthermore, the solid content of the monodisperse polymer seed solution is 5-20 wt %; and / or the mass ratio of the monodisperse polymer seed solution to the first vinyl monomer is 1:1-100.

[0012] Furthermore, the mass ratio of the first water to the polymer seed solution is 0.8-1:1; and / or the mass ratio of the second water to the first vinyl monomer is 100-4000:100; and / or the mass ratio of the third water to the second vinyl monomer is 200-1500:100.

[0013] Furthermore, in step S2, the temperature of the first swelling is 5 to 40°C and the time is 5 to 20 hours.

[0014] Furthermore, in step S3, the temperature of the first polymerization reaction is 60-80°C and the time is 10-20 hours; and / or, the time of the second swelling is 5-40°C and the time is 5-48 hours; and / or, the second reaction liquid system is added with a stabilizer solution and mixed before the first polymerization reaction is carried out, and the stabilizer solution is preferably an aqueous solution of polyvinyl alcohol.

[0015] Furthermore, in step S3, the temperature of the second polymerization reaction is 60-80°C and the time is 10-20 hours; and / or, in step S3, the temperature of the third swelling reaction is 5-40°C and the time is 5-48 hours.

[0016] In a second typical embodiment of the present application, a core-shell porous polymer microsphere is further provided. The core-shell porous polymer microsphere is obtained according to the preparation method provided in the first aspect above.

[0017] Furthermore, the particle size of the core-shell porous polymer microspheres is 5 to 100 μm.

[0018] According to the third aspect of the present application, there is also provided the application of the core-shell porous polymer microspheres in the field of chromatographic separation.

[0019] By applying the technical solution of the present application, the preparation method of core-shell porous polymer microspheres provided in the present application can regulate the particle size of the porous polymer microspheres and the thickness of the core layer and shell layer by selecting the size of the polymer seed particles, the amount of the first vinyl monomer, and the amount of the second vinyl monomer. At the same time, it can also control the size of the pore size of the microsphere core layer by controlling the dosage ratio of the first porogen to the first vinyl monomer, and control the size of the pore size of the microsphere shell layer by controlling the dosage ratio of the second porogen to the second vinyl monomer, thereby realizing the controllable preparation of monodisperse core-shell porous polymer microspheres, and thus obtaining core-shell porous polymer microspheres with highly uniform particle size and widely adjustable particle size from 5 to 100 μm.

[0020] In addition, the preparation method of the core-shell porous polymer microspheres provided in the present application is simple in process and easy to operate, which is more conducive to large-scale production and further reduces production costs. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] The drawings that constitute part of this application are used to provide a further understanding of this application. The illustrative embodiments of this application and their descriptions are used to explain this application and do not constitute an improper limitation on this application. In the drawings:

[0022] FIG1 shows the particle size distribution of monodisperse core-shell porous polymer microspheres with a particle size of 20 μm provided in Example II-1 of the present application;

[0023] FIG2 shows a SEM image of the external morphology of monodisperse core-shell porous polymer microspheres with a particle size of 20 μm provided in Example II-1 of the present application;

[0024] FIG3 shows a SEM image of the interior of monodisperse core-shell porous polymer microspheres with a particle size of 20 μm provided in Example II-1 of the present application;

[0025] FIG4 shows the particle size distribution of 50 μm monodispersed core-shell porous polymer microspheres provided in Example III-1 of the present application. DETAILED DESCRIPTION

[0026] It should be noted that, in the absence of conflict, the embodiments and features of the embodiments in this application can be combined with each other. The present application will be described in detail below with reference to the embodiments.

[0027] As analyzed in the background technology of this application, the surface of the core-shell porous polymer microspheres has a small-sized pore structure, and the internal core is a large-sized pore structure. The non-uniform distribution of pore size from the outside to the inside makes the controllable preparation of core-shell porous polymer microspheres face huge challenges. The most commonly used synthesis techniques at present are suspension polymerization and seed swelling method. Due to the wide droplet size distribution and large particle size in the suspension before polymerization, the suspension polymerization method leads to problems such as wide particle size distribution, poor monodispersity, and large particle size of the porous microspheres after polymerization. It is difficult to prepare highly uniform monodispersity and porous microspheres with a particle size of less than 20μm. In order to solve this problem, the present application provides a core-shell porous polymer microsphere and a preparation method and application thereof.

[0028] In a first typical embodiment of the present application, a method for preparing core-shell porous polymer microspheres is provided, which comprises: step S1, mixing a first porogen, a first water, an optional first surfactant and an optional first cosolvent to obtain a first emulsion; mixing a first vinyl monomer, a first initiator, a second water and an optional second surfactant to obtain a second emulsion; mixing a second vinyl monomer, a second porogen, a second initiator, a third water and an optional third surfactant to obtain a third emulsion; step S2, mixing the first emulsion and a monodisperse polymer seed solution, and performing a first swelling to obtain a first reaction liquid system; step S3, mixing the first reaction liquid system and the second emulsion, and performing a second swelling to obtain a second reaction liquid system, and further performing a first polymerization reaction on the second reaction liquid system to obtain a third reaction liquid system; step S4, mixing the third reaction liquid system and the third emulsion, and performing a third swelling, and further performing a second polymerization reaction to obtain a fourth reaction liquid system; step S5, purifying the fourth reaction liquid system, and removing the first porogen and the second porogen to obtain core-shell porous polymer microspheres.

[0029] The preparation method of core-shell porous polymer microspheres provided in the present application can regulate the particle size of the porous polymer microspheres and the thickness of the core layer and shell layer by selecting the size of the polymer seed particles, the amount of the first vinyl monomer, and the amount of the second vinyl monomer. At the same time, the pore size of the microsphere core layer can be controlled by controlling the dosage ratio of the first porogen to the first vinyl monomer, and the pore size of the microsphere shell layer can be controlled by controlling the dosage ratio of the second porogen to the second vinyl monomer, thereby achieving the controllable preparation of monodisperse core-shell porous polymer microspheres, and thus obtaining core-shell porous polymer microspheres with highly uniform particle size and a widely adjustable particle size from 5 to 100 μm.

[0030] In addition, the preparation method of the core-shell porous polymer microspheres provided in the present application is simple in process and easy to operate, which is more conducive to large-scale production and further reduces production costs.

[0031] [First porogen and second porogen]

[0032] In the present application, the first porogen and the second porogen are each a porogen commonly used in the art, such as a small molecule porogen or an oligomer porogen such as a saturated alkane, a fatty alcohol, or a chlorinated hydrocarbon, and are not described in detail here. Furthermore, the first porogen and the second porogen can be the same or different.

[0033] Specifically, the first porogen and the second porogen are each independently a mixture of any one or more of dibutyl phthalate, toluene, cyclohexanol or 2-ethylhexanoic acid.

[0034] [First surfactant, second surfactant, third surfactant]

[0035] The first surfactant, the second surfactant, and the third surfactant are all commonly used surfactants in the art, and can be identical or completely different. Specifically, the first surfactant, the second surfactant, and the third surfactant are each independently a mixture of one or more of sodium lauryl sulfate, sodium dodecylbenzenesulfonate, polyvinyl pyrrolidone, or polyvinyl alcohol.

[0036] [Polymer seed solution]

[0037] The material of the polymer seed in the monodisperse polymer seed solution is not particularly limited, and any polymer seed of microspheres commonly used in the art can be used. Specifically, the polymer seed material is a copolymer formed by any one or more of polystyrene, polyacrylate, polystyrene acrylic latex particles, or functionalized polystyrene.

[0038] In addition, depending on the different particle sizes of the core-shell porous polymer microspheres to be prepared, the particle size of the polymer seeds in the monodisperse polymer seed solution is also different. In some embodiments, the particle size of the polymer seeds is 0.5 to 20 μm, such as 0.5 μm, 1 μm, 3 μm, 5 μm, 7 μm, 10 μm, 12 μm, 15 μm, 18 μm, 20 μm or a range of any two values.

[0039] [First cosolvent]

[0040] The first cosolvent is used to disperse the monodisperse polymer seed solution to prevent agglomeration or sedimentation of the polymer seed solution, which could affect the uniformity of the particle size of the porous polymer microspheres subsequently prepared. If the monodisperse polymer seed solution can remain stably dispersed in water, the first cosolvent may not be added.

[0041] The specific type of the first cosolvent is not limited, and any commonly used cosolvent in the art can be used. Specifically, the first cosolvent is a mixture of any one or more of acetone, butanol, 1-chlorodecane, or chlorobenzene.

[0042] [First vinyl monomer and second vinyl monomer]

[0043] The first vinyl monomer and the second vinyl monomer are independently any one or more vinyl monomers commonly used in the art, including but not limited to styrene, divinylbenzene, methyl methacrylate, glycidyl methacrylate or acrylonitrile (forming a copolymer).

[0044] [First initiator and second initiator]

[0045] The first initiator can be selected from different substances according to the first vinyl monomer. For example, if the first vinyl monomer is styrene, the first initiator is a peroxide, which includes but is not limited to a mixture of any one or more of benzoyl peroxide, tert-butyl benzoyl peroxide or methyl ethyl ketone peroxide.

[0046] The second initiator can be selected from different substances depending on the second vinyl monomer. For example, when the second vinyl monomer is a mixture of styrene and dienylbenzene, the second initiator is a peroxide. The type of the peroxide is as described in the first initiator above and will not be repeated here.

[0047] In order to prepare porous polymer microspheres with moderate pore size and porosity in the core layer, the mass ratio of the first porogen to the first vinyl monomer is preferably 5 to 25:100, more preferably 10 to 20:100, such as 5:100, 8:100, 10:100, 15:100, 20:100, 25:100 or a range value consisting of any two values.

[0048] In order to prepare porous polymer microspheres with moderate pore size and porosity in the shell layer, the mass ratio of the second porogen to the second vinyl monomer is preferably 50-200:100, more preferably 85-95:100, such as 50:100, 60:100, 70:100, 75:100, 85:100, 90:100, 95:100, 100:100, 120:100, 150:100, 200:100 or a range value consisting of any two values.

[0049] In order to prepare porous polymer microspheres with a reasonable core-shell thickness distribution, the mass ratio of the first vinyl monomer to the second vinyl monomer is preferably 15 to 100:100, more preferably 30 to 60:100, such as 15:100, 20:100, 25:100, 30:100, 45:100, 60:100, 70:100, 80:100, 90:100, 100:100 or a range value consisting of any two values.

[0050] In some embodiments, the solid content of the monodisperse polymer seed solution is 5 to 20 wt%, and more preferably 5 to 15 wt% (such as 5 wt%, 10 wt%, 15 wt%, 20 wt% or a range consisting of any two values), so as to further improve the dispersion stability of the monodisperse polymer seed solution.

[0051] In other embodiments, the mass ratio of the monodisperse polymer seed solution to the first vinyl monomer is 1:1 to 100 (such as 1:1, 1:2, 1:3, 1:5, 1:10, 1:20, 1:50, 1:100, etc.), so as to facilitate the preparation of porous polymer microspheres with higher particle size uniformity.

[0052] In order to further improve the particle size uniformity of the porous polymer microspheres, the mass ratio of the first water to the polymer seed solution is preferably 0.8-1:1, more preferably 0.85-0.95:1 (such as 0.85:1, 0.87:1, 0.89:1, 0.92:1, etc.); and / or, the mass ratio of the second water to the first vinyl monomer is 100-4000, more preferably 100-1500:100 (such as 100:100, 500:100, 1000:100, 1500:100, etc.); and / or, the mass ratio of the third water to the second vinyl monomer is 200-1500, more preferably 600-900:100 (such as 600:100, 700:100, 800:100, 900:100, etc.).

[0053] When preparing core-shell porous polymer microspheres with a particle size of 5 μm, in some specific embodiments, the mass ratio of the first vinyl monomer to the second vinyl monomer is 1:2 to 2.5; the mass ratio of the monodisperse polystyrene solution (solid content of 10 to 15 wt%) to the first vinyl monomer is 1:1 to 1.5; the mass ratio of the first water to the polymer seed solution is 0.8 to 0.9:1; the mass ratio of the second water to the first vinyl monomer is 1500 to 2500:100; and the mass ratio of the third water to the second vinyl monomer is 500 to 1500:100.

[0054] When preparing core-shell porous polymer microspheres with a particle size of 20 μm, in some specific embodiments, the mass ratio of the first vinyl monomer to the second vinyl monomer is 1:1.5~2.5; the mass ratio of the monodisperse polystyrene solution (solid content of 5~15wt%) to the first vinyl monomer is 1:1.5~2.5; the mass ratio of the first water to the polymer seed solution is 0.8~0.95:1; the mass ratio of the second water to the first vinyl monomer is 2000~4000:100; and the mass ratio of the third water to the second vinyl monomer is 800~1500:100.

[0055] When preparing core-shell porous polymer microspheres with a particle size of 50 μm, in some specific embodiments, the mass ratio of the first vinyl monomer to the second vinyl monomer is 1:2.0-2.5; the mass ratio of the monodisperse polystyrene solution (solid content of 5-15 wt%) to the first vinyl monomer is 1:15-25; the mass ratio of the first water to the polymer seed solution is 0.8-0.9:1; the mass ratio of the second water to the first vinyl monomer is 500-2000:100; and the mass ratio of the third water to the second vinyl monomer is 500-1000:100.

[0056] When preparing 100 μm core-shell porous polymer microspheres, in some specific embodiments, the mass ratio of the first vinyl monomer to the second vinyl monomer is 1:3 to 5; the mass ratio of the monodisperse polystyrene solution (solid content of 5 to 15 wt%) to the first vinyl monomer is 1:20 to 40; the mass ratio of the first water to the polymer seed solution is 0.8 to 0.9:1; the mass ratio of the second water to the first vinyl monomer is 500 to 2000:100; and the mass ratio of the third water to the second vinyl monomer is 600 to 1000:100.

[0057] In order to avoid introducing impurities that may affect the separation performance of the porous polymer microspheres, it is preferred that the first water, the second water, and the third water are each independently deionized water.

[0058] In the above steps S2, S3 and S4, in order to further improve the particle size uniformity of the porous polymer microspheres, it is preferred that the temperatures of the first swelling, the second swelling and the third swelling are each independently 5 to 40°C (such as 5°C, 8°C, 10°C, 15°C, 20°C, 30°C, 40°C), and the time is 5 to 48 hours (5h, 10h, 24h, 36h, 48h).

[0059] In order to further improve the particle size uniformity of the porous polymer microspheres, the above-mentioned step S3 is preferably performed at a temperature of 60 to 80°C (such as 60°C, 65°C, 70°C, 75°C, 80°C) and a time of 10 to 20h (such as 10h, 12h, 15h, 18h, 20h).

[0060] In the above step S3, in order to further improve the uniformity and stability of the first reaction liquid system and the second emulsion mixture, it is preferred that a stabilizer is added to the second reaction liquid system before the first polymerization reaction. The stabilizer solution includes but is not limited to an aqueous solution of polyvinyl alcohol.

[0061] In the above step S4, in order to further improve the efficiency of the second polymerization reaction, the temperature of the second polymerization reaction is preferably 60-80°C (such as 60°C, 65°C, 70°C, 75°C, 80°C), and the time is 10-20h (such as 10h, 12h, 15h, 18h, 20h).

[0062] In step S5, the purification method is not specifically limited and may be any commonly used method in the art, including but not limited to solid-liquid separation, washing, and screening. Examples of solid-liquid separation methods include centrifugation or filtration. The specific method for removing the first and second porogens is also not limited and may include but not limited to extraction and soaking.

[0063] In a second typical embodiment of the present application, a core-shell porous polymer microsphere is provided, which is obtained by the preparation method of the core-shell porous polymer microsphere provided in the first typical embodiment.

[0064] The core-shell porous polymer microspheres provided in the present application not only have controllable thickness of the core layer and shell layer and pore size, but also have a controllable and highly uniform particle size range, and have broad application prospects in the field of chromatographic separation.

[0065] In some specific embodiments, the core-shell porous polymer microspheres have a particle size of 5 to 100 μm, such as 5 μm, 10 μm, 20 μm, 50 μm, 80 μm, 100 μm, or a range consisting of any two values.

[0066] The beneficial effects of the present application will be further illustrated below with reference to the embodiments.

[0067] (1) Preparation of 5 μm monodispersed core-shell porous polymer microspheres

[0068] Example I-1

[0069] This embodiment provides a method for preparing 5 μm monodisperse core-shell porous polymer microspheres, which is carried out according to the following steps:

[0070] (1) 0.25 g of sodium lauryl sulfate, 0.8 g of dibutyl phthalate, 10 g of acetone, and 100 g of purified water were homogenized under high pressure to form a first emulsion; 0.3 g of sodium lauryl sulfate, 5 g of styrene, 0.2 g of benzoyl peroxide, and 120 g of purified water were homogenized under high pressure to form a second emulsion; 0.3 g of sodium lauryl sulfate, 5 g of styrene, 5 g of divinylbenzene, 15 g of dibutyl phthalate, 0.1 g of benzoyl peroxide, and 120 g of purified water were homogenized under high pressure to form a third emulsion;

[0071] (2) The first emulsion was added to a 1 L four-necked flask, and 5 g of a monodispersed polystyrene seed solution (polystyrene seed particle size of 0.8 μm, solid content of 6 wt%) was added under stirring, and the mixture was stirred and swollen at room temperature for 16 h to obtain a first reaction liquid system;

[0072] (3) The second emulsion was added to the first reaction liquid system and stirred at room temperature for 5 hours to obtain a second reaction liquid system. 36 g of PVA (model 0588) aqueous solution was added to the second reaction liquid system, stirred at room temperature for 1 hour, and then reacted at 70°C for 16 hours to obtain a third reaction liquid system.

[0073] (4) The third emulsion was added to the third reaction liquid system and swelled at room temperature for 5 hours, and finally reacted at 70°C for 16 hours. The polymerization was completed to obtain the fourth reaction liquid system.

[0074] (5) The fourth reaction liquid system is centrifuged, washed, extracted, sieved and filtered to obtain monodisperse core-shell porous polymer microspheres with a particle size of 5 μm.

[0075] Example I-2

[0076] The difference between this embodiment and embodiment 1 is that in step (1), in the first emulsion, the amount of dibutyl phthalate is adjusted so that the mass ratio of dibutyl phthalate to styrene in the second emulsion is 1:5; in the third emulsion, the amount of dibutyl phthalate is adjusted so that the mass ratio of dibutyl phthalate to styrene in the third emulsion is 1:1.

[0077] Example I-3

[0078] The difference between this embodiment and embodiment 1 is that in step (1), in the first emulsion, the amount of dibutyl phthalate is adjusted so that the mass ratio of dibutyl phthalate to styrene in the second emulsion is 1:10; and in the third emulsion, the amount of dibutyl phthalate is adjusted so that the mass ratio of dibutyl phthalate to styrene in the third emulsion is 2:1.

[0079] Example I-4

[0080] The difference between this embodiment and embodiment 1 is that in step (2), the swelling time is 20 hours; in step (3), the swelling time is 20 hours; and in step (4), the swelling time is 20 hours.

[0081] Example I-5

[0082] The difference between this embodiment and embodiment 1 is that in step (3), the swelling time is 5 h; in step (3), the swelling time is 5 h; and in step (4), the swelling time is 5 h.

[0083] Example I-6

[0084] The difference between this embodiment and embodiment 1 is that in step (2), the swelling time is 2 hours; in step (3), the swelling time is 2 hours; and in step (4), the swelling time is 2 hours.

[0085] Comparative Example I-1

[0086] The difference between this embodiment and embodiment 1 is that no swelling treatment is performed in step (2), step (3) and step (4).

[0087] Test Example 1

[0088] The 5 μm monodisperse core-shell porous polymer microspheres provided in the Examples and Comparative Examples were tested for particle size uniformity, with the results shown in Table 1. The particle size was determined by ultrasonically dispersing 0.5 g of the filtered microspheres in 10 g of deionized water. The microsphere dispersion was then added to the sample cell of a laser particle size analyzer to obtain the particle size distribution of the microspheres.

[0089] Table 1

[0090] (2) Preparation of 20 μm monodispersed core-shell porous polymer microspheres

[0091] Example II-1

[0092] This embodiment provides a method for preparing 20 μm monodisperse core-shell porous polymer microspheres, which is carried out according to the following steps:

[0093] (1) 0.3 g of sodium lauryl sulfate, 0.9 g of dibutyl phthalate, 12 g of acetone, and 120 g of purified water were homogenized under high pressure to form a first emulsion; 0.3 g of sodium lauryl sulfate, 8.8 g of styrene, 0.2 g of benzoyl peroxide, and 120 g of purified water were homogenized under high pressure to form a second emulsion; 0.3 g of sodium lauryl sulfate, 10 g of styrene, 10 g of divinylbenzene, 14 g of dibutyl phthalate, 0.2 g of benzoyl peroxide, and 120 g of purified water were homogenized under high pressure to form a third emulsion;

[0094] (2) The first emulsion was added to a 1 L four-necked flask, and 3.6 g of a monodispersed polystyrene seed (polystyrene seed particle size of 4.5 μm, solid content of 10 wt%) aqueous solution was added under stirring, and the mixture was stirred and swelled at room temperature for 16 h to obtain a first reaction liquid system.

[0095] (3) The second emulsion was added to the first reaction solution and stirred at room temperature for 5 h to obtain a second reaction solution. 36 g of PVA aqueous solution was then added to the second reaction solution, stirred for 1 h, and then reacted at 70°C for 16 h to obtain a third reaction solution.

[0096] (4) The third reaction liquid was added to the third reaction liquid system and swelled at room temperature for 5 hours, and finally reacted at 75° C. for 16 hours. The polymerization was completed to obtain the fourth reaction liquid system.

[0097] (5) The fourth reaction liquid system is centrifuged, washed, extracted, sieved and filtered to obtain monodisperse core-shell porous polymer microspheres with a particle size of 20 μm.

[0098] Example II-2

[0099] This embodiment provides a method for preparing 20 μm monodisperse core-shell porous polymer microspheres, which is carried out according to the following steps:

[0100] (1) 0.5 g of sodium dodecylbenzene sulfonate, 0.5 g of dibutyl phthalate, 12 g of acetone and 120 g of purified water were homogenized under high pressure to form a first emulsion; 0.5 g of sodium dodecylbenzene sulfonate, 6 g of styrene, 0.2 g of benzoyl peroxide and 120 g of purified water were homogenized under high pressure to form a second emulsion; 0.5 g of sodium dodecylbenzene sulfonate, 10 g of styrene, 10 g of divinylbenzene, 12 g of cyclohexanol, 0.2 g of benzoyl peroxide and 120 g of purified water were homogenized under high pressure to form a third emulsion.

[0101] (2) The first emulsion was added to a 1 L four-necked flask, and 3.6 g of a monodispersed polystyrene seed (polystyrene seed particle size of 4.5 μm, solid content of 8 wt%) aqueous solution was added under stirring, and the mixture was stirred and swelled at room temperature for 20 h to obtain a first reaction liquid system.

[0102] (3) The second reaction solution was added to the first reaction solution system and stirred at room temperature for 6 hours to obtain a second reaction solution system. 36 g of PVA aqueous solution was then added to the second reaction solution system, stirred for 1 hour, and then reacted at 65°C for 16 hours to obtain a third reaction solution system.

[0103] (4) The third emulsion was added to the third reaction liquid system and swelled at room temperature for 5 hours, and finally reacted at 70°C for 16 hours. The polymerization was completed to obtain the fourth reaction liquid system.

[0104] (5) The fourth reaction liquid system is centrifuged, washed, extracted, sieved and filtered to obtain monodisperse core-shell porous polymer microspheres with a particle size of 20 μm.

[0105] Example II-3

[0106] The difference between this embodiment and embodiment 1 is that in step (1), in the first emulsion, the amount of dibutyl phthalate is adjusted so that the mass ratio of dibutyl phthalate to styrene in the second emulsion is 1:7; in the third emulsion, the amount of dibutyl phthalate is adjusted so that the mass ratio of dibutyl phthalate to styrene in the third emulsion is 2:1.

[0107] Example II-4

[0108] The difference between this embodiment and embodiment 1 is that in step (1), in the first emulsion, the amount of dibutyl phthalate is adjusted so that the mass ratio of dibutyl phthalate to styrene in the second emulsion is 1:6; in the third emulsion, the amount of dibutyl phthalate is adjusted so that the mass ratio of dibutyl phthalate to styrene in the third emulsion is 1.5:1.

[0109] Example II-5

[0110] The difference between this embodiment and embodiment 1 is that in step (2), the swelling time is 20 hours; in step (3), the swelling time is 20 hours; and in step (4), the swelling time is 20 hours.

[0111] Example II-6

[0112] The difference between this embodiment and embodiment 1 is that in step (3), the swelling time is 5 h; in step (3), the swelling time is 5 h; and in step (4), the swelling time is 5 h.

[0113] Example II-7

[0114] The difference between this embodiment and embodiment 1 is that in step (2), the swelling time is 2 hours; in step (3), the swelling time is 2 hours; and in step (4), the swelling time is 2 hours.

[0115] Comparative Example II-1

[0116] The difference between this embodiment and embodiment 1 is that no swelling treatment is performed in step (2), step (3) and step (4).

[0117] Test Example 2

[0118] The monodisperse core-shell porous polymer microspheres with a particle size of 20 μm provided in Example II-1 were subjected to a particle size distribution test, and the results are shown in Figure 1. At the same time, the monodisperse core-shell porous polymer microspheres with a particle size of 20 μm provided in Example II-1 were also subjected to scanning electron microscopy, and the resulting SEM images are shown in Figures 2 and 3. As can be seen from Figure 1, the monodisperse core-shell porous polymer microspheres with a particle size of 20 μm provided in Example II-1 have highly uniform particle sizes and good monodispersity. As can be seen from Figures 2 and 3, the porous polymer microspheres have a rich surface microporous structure and a through-hole macroporous structure inside.

[0119] Test Example 3

[0120] The 20 μm monodisperse core-shell porous polymer microspheres provided in the Examples and Comparative Examples were tested for particle size uniformity, with the results shown in Table 2. The particle size was determined by ultrasonically dispersing 0.5 g of the filtered microspheres in 10 g of deionized water. The microsphere dispersion was then added to the sample cell of a laser particle size analyzer to obtain the particle size distribution of the microspheres.

[0121] Table 2

[0122] (III) Preparation of 50 μm monodispersed core-shell porous polymer microspheres

[0123] Example III-1

[0124] This embodiment provides a method for preparing 50 μm monodisperse core-shell porous polymer microspheres, which is carried out according to the following steps:

[0125] (1) 0.3 g of sodium lauryl sulfate, 7 g of dibutyl phthalate, 12 g of acetone, and 120 g of purified water were homogenized under high pressure to form a first emulsion; 1 g of sodium lauryl sulfate, 75 g of styrene, 2 g of benzoyl peroxide, and 360 g of purified water were homogenized under high pressure to form a second emulsion; 1.2 g of sodium lauryl sulfate, 84 g of styrene, 100 g of divinylbenzene, 110 g of dibutyl phthalate, 1.6 g of benzoyl peroxide, and 1500 g of purified water were homogenized under high pressure to form a third emulsion;

[0126] (2) The first emulsion was added to a 5 L four-necked flask, and 3.6 g of a monodispersed polystyrene seed solution (polystyrene seed particle size of 4.5 μm, solid content of 8 wt%) was added under stirring, and the mixture was stirred and swollen at room temperature for 10 h to obtain a first reaction liquid system;

[0127] (3) The second emulsion was added to the first reaction solution system and stirred at room temperature for 24 hours to obtain a second reaction solution system. 100 g of PVA aqueous solution was then added to the second reaction solution system, stirred for 1 hour, and then reacted at 75°C for 16 hours to obtain a third reaction solution system.

[0128] (4) The third emulsion was added to the third reaction liquid system and swelled at room temperature for 36 hours, and finally reacted at 75°C for 16 hours. The polymerization was completed to obtain the fourth reaction liquid system.

[0129] (5) The fourth reaction liquid system is centrifuged, washed, extracted, sieved and filtered to obtain monodisperse core-shell porous polymer microspheres with a particle size of 50 μm.

[0130] The particle size distribution of the monodisperse core-shell porous polymer microspheres with a particle size of 50 μm provided in Example III-1 was tested. As shown in FIG4 , D25 was 46.07 μm, D50 was 50.23 μm, D75 was 60.26 μm, and D90 was 68.59 μm.

[0131] (IV) Preparation of 100 μm monodispersed core-shell porous polymer microspheres

[0132] Example IV-1

[0133] This embodiment provides a method for preparing 100 μm monodisperse core-shell porous polymer microspheres, which is carried out according to the following steps:

[0134] (1) 0.5 g of sodium lauryl sulfate, 7.0 g of dibutyl phthalate, 12 g of acetone, and 120 g of purified water were homogenized under high pressure to form a first emulsion; 1.5 g of sodium lauryl sulfate, 75 g of styrene, 4 g of benzoyl peroxide, and 360 g of purified water were homogenized under high pressure to form a second emulsion; 2.5 g of sodium lauryl sulfate, 150 g of styrene, 150 g of divinylbenzene, 200 g of dibutyl phthalate, 3.0 g of benzoyl peroxide, and 3000 g of purified water were homogenized under high pressure to form a third emulsion;

[0135] (2) The first emulsion was added to a 10 L reactor, and 2 g of a monodispersed polystyrene seed solution (polystyrene seed particle size of 10 μm, solid content of 6 wt%) was added under stirring, and the mixture was stirred and swollen at room temperature for 10 h to obtain a first reaction liquid system;

[0136] (3) The second emulsion was added to the first reaction solution system and stirred at room temperature for 24 hours to obtain a second reaction solution system. 300 g of PVA aqueous solution was then added to the second reaction solution system, stirred for 1 hour, and then reacted at 75°C for 16 hours to obtain a third reaction solution system.

[0137] (4) The third emulsion was added to the third reaction liquid system and swelled at room temperature for 48 hours, and finally reacted at 75°C for 16 hours. The polymerization was completed to obtain the fourth reaction liquid system.

[0138] (5) The fourth reaction liquid system is centrifuged, washed, extracted, sieved and filtered to obtain monodisperse core-shell porous polymer microspheres with a particle size of 100 μm.

[0139] The monodisperse core-shell porous polymer microspheres with a particle size of 50 μm provided in Example IV-1 were subjected to particle size distribution testing. The results showed that D25 was 91.91 μm, D50 was 100.30 μm, D75 was 115.1 μm, and D90 was 135.4 μm.

[0140] From the above description, it can be seen that the above-mentioned embodiments of the present application achieve the following technical effects: the preparation method of core-shell porous polymer microspheres provided in the present application can regulate the size of the porous polymer microsphere particle size and the thickness of the core layer and shell layer by selecting the size of the polymer seed particle size, the amount of the first vinyl monomer, and the amount of the second vinyl monomer. At the same time, it can also control the size of the pore size of the microsphere core layer by controlling the dosage ratio of the first porogen to the first vinyl monomer, and control the size of the pore size of the microsphere shell layer by controlling the dosage ratio of the second porogen to the second vinyl monomer, thereby realizing the controllable preparation of monodisperse core-shell porous polymer microspheres, and thus obtaining core-shell porous polymer microspheres with highly uniform particle size and widely adjustable particle size from 5 to 100 μm.

[0141] In addition, the preparation method of the core-shell porous polymer microspheres provided in the present application is simple in process and easy to operate, which is more conducive to large-scale production and further reduces production costs.

[0142] The above description is merely a preferred embodiment of the present application and is not intended to limit the present application. Various modifications and variations are possible for those skilled in the art. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present application shall be included within the scope of protection of the present application.

Claims

1. A method for preparing a core-shell porous polymer microsphere, characterized in that, The preparation method includes: Step S1: Mix a first porogen, first water, an optional first surfactant, and an optional first cosolvent to obtain a first emulsion; mix a first vinyl monomer, a first initiator, second water, and an optional second surfactant to obtain a second emulsion; mix a second vinyl monomer, a second porogen, a second initiator, third water, and an optional third surfactant to obtain a third emulsion. Step S2: Mix the first emulsion and a monodisperse polymer seed solution and perform first swelling to obtain a first reaction liquid system. Step S3: Mix the first reaction liquid system and the second emulsion and perform second swelling to obtain a second reaction liquid system, and perform a first polymerization reaction on the second reaction liquid system to obtain a third reaction liquid system. Step S4: Mix the third reaction liquid system and the third emulsion and perform third swelling, and then perform a second polymerization reaction to obtain a fourth reaction liquid system. Step S5: Purify the fourth reaction liquid system and remove the first porogen and the second porogen to obtain the core-shell porous polymer microspheres.

2. The preparation method according to claim 1, characterized in that, The first porogen and the second porogen are each independently selected from at least one of dibutyl phthalate, toluene, cyclohexanol, or 2-ethylhexanoic acid. And / or, the first surfactant, the second surfactant, and the third surfactant are each independently selected from at least one of sodium dodecyl sulfate, sodium dodecylbenzenesulfonate, polyvinylpyrrolidone, or polyvinyl alcohol. And / or, the material of the polymer seeds in the polymer seed solution is selected from at least one of polystyrene, polyacrylate, polystyrene-propylene latex particles, or functionalized polystyrene. And / or, the particle size of the polymer seeds in the polymer seed solution is 0.5 - 20 μm. And / or, the first cosolvent is selected from at least one of acetone, butanol, 1-chlorodecane, or chlorobenzene. And / or, the first vinyl monomer and the second vinyl monomer are each independently at least one of styrene, divinylbenzene, methyl methacrylate, glycidyl methacrylate, or acrylonitrile. And / or, the first initiator and the second initiator are each independently at least one of peroxides or azo compounds. The peroxides are selected from at least one of benzoyl peroxide, tert-butyl peroxybenzoate, or methyl ethyl ketone peroxide. The azo compounds include at least one of azobisisobutyronitrile or azobisisoheptonitrile.

3. The preparation method according to claim 1, wherein, The mass ratio of the first porogen to the first vinyl monomer is 5 - 25:

100. And / or, the mass ratio of the second porogen to the second vinyl monomer is 50 - 200:

100. And / or, the mass ratio of the first vinyl monomer to the second vinyl monomer is 15 - 100:

100.

4. The preparation method according to claim 1, characterized in that, The solid content of the monodisperse polymer seed solution is 5 - 20 wt%. And / or, the mass ratio of the monodisperse polymer seed solution to the first vinyl monomer is 1:1 - 100.

5. The preparation method according to claim 1, characterized in that, The mass ratio of the first water to the polymer seed solution is 0.8 - 1:

1. And / or, the mass ratio of the second water to the first vinyl monomer is 100 - 4000:100; And / or, the mass ratio of the third water to the second vinyl monomer is 200 - 1500:

100.

6. The preparation method according to claim 1, characterized in that, In the step S2, the temperature of the first swelling is 5 - 40 °C, and the time is 5 - 20 h.

7. The preparation method according to claim 1, characterized in that, In the step S3, the temperature of the first polymerization reaction is 60 - 80 °C, and the time is 10 - 20 h; And / or, the temperature of the second swelling is 5 - 40 °C, and the time is 5 - 48 h; And / or, after the second reaction liquid system is mixed with the stabilizer solution, the first polymerization reaction is carried out.

8. The preparation method according to any one of claims 1 to 7, characterized in that In the step S3, the temperature of the second polymerization reaction is 60 - 80 °C, and the time is 10 - 20 h; And / or, in the step S3, the temperature of the third swelling is 5 - 40 °C, and the time is 5 - 48 h.

9. A core-shell porous polymer microsphere, characterized in that, The core-shell porous polymer microspheres are obtained according to the preparation method described in any one of claims 1 to 8.

10. Application of the core-shell porous polymer microspheres described in claim 9 in the field of chromatographic separation.

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