Monodisperse polymer porous microsphere and preparation method thereof

Abstract

The invention discloses a monodisperse polymer porous microsphere and a preparation method thereof, the preparation method comprises the following two steps: 1, seed microsphere swelling: carrying out ultrasonic emulsification swelling on an emulsifier, a pore-foaming agent, a swelling agent, monomer styrene and a cross-linking agent divinyl benzene, and reaching swelling equilibrium after a period of time; and 2, adding a stabilizer, and heating to enable styrene and divinyl benzene to generate polymerization reaction to obtain larger polymer microspheres. The particle size of the polymerized microspheres can reach 10-20 microns, the uniformity is good, the requirements of monodisperse microspheres can be met, and the experimental method is easy and convenient to operate, good in process stability and reproducibility and very suitable for industrial production.

Description

Technical Field

[0001] The present invention belongs to the technical field of polymer microspheres, and in particular relates to monodisperse polymer porous microspheres and a preparation method thereof. Background Art

[0002] Polystyrene-divinylbenzene (PS / DVB) microspheres are polymer microspheres produced through the polyaddition reaction of styrene and divinylbenzene. They exhibit advantages such as good sphericity, large specific surface area, high mechanical strength, and excellent stability. They also possess unique properties, such as uniform and controllable pore and particle sizes within a certain range. These unique properties, compared to other materials, have led to a growing range of applications, including in information technology, targeted therapy, medical aesthetics, chromatography, protein purification, and environmental remediation.

[0003] The seed swelling method is currently the most suitable for industrial production of large-particle monodisperse polymer microspheres. Companies utilizing this method include Suzhou Nanovitamin Technology and Suzhou Zhiyi Microspheres. The seed swelling polymerization process can be broadly divided into two steps: first, a swelling agent, such as styrene and an initiator, is continuously added to the seed microspheres, causing them to swell until equilibrium is reached. Second, the temperature is raised to induce polymerization of the styrene and other agents, resulting in larger, cross-linked polymer microspheres. Therefore, seed microspheres must be prepared before the swelling polymerization reaction. These are typically generated by dissolving styrene, an initiator, and a dispersant in a dispersion medium. Once the polymer chains grow to a certain molecular weight, they are stabilized by the dispersant to form small microspheres, resulting in monodisperse, non-cross-linked polymer microsphere seeds. The seed swelling polymerization process then begins.

[0004] CN118930743A currently discloses a method for preparing monodisperse polymer microspheres with a size of less than 10 μm. The following steps are as follows: S1. Monodisperse polystyrene microspheres, a stabilizer, an ionic liquid, and a low-boiling-point organic compound are added to water, mixed uniformly, and stirred to swell to obtain a seed swelling solution; S2. An oil-soluble initiator is added to vinyl styrene and ultrasonically dispersed to obtain a styrene mixed solution; S3. The styrene mixed solution is added to the seed swelling solution and stirred to swell to obtain a seed reaction solution; S4. The seed reaction solution is bubbling with nitrogen and reacting at a controlled temperature to obtain a suspension. After centrifugation, washing, and drying, large-sized monodisperse polystyrene microspheres are obtained. This preparation method is complex, and post-processing of residual reagents is difficult. Furthermore, the resulting polystyrene microspheres exhibit surface defects and a small particle size, as shown by SEM results, and cannot meet the high requirements of industries such as biomedicine and testing.

[0005] Furthermore, CN1038756C discloses a method for producing particles with a uniform particle size range of 1 to 50 microns. The method comprises mixing styrene or a styrene mixture with a polymer seed particle dispersion under certain conditions, then maintaining the temperature above the initiator activation temperature to allow the particles to grow to a selected size and until the styrene is fully polymerized. These steps are repeated until the target particle size is reached. This technical solution employs difficult-to-control techniques such as adjusting the feed rate based on reaction kinetics, repeated temperature increases and decreases, and screen filtration. Consequently, in practical applications, this solution suffers from poor batch stability, difficulty controlling the size of each batch, low production efficiency, and the need to handle a swelling agent.

[0006] As can be seen from the above, the current processes for preparing large-particle PS-DVB microspheres all suffer from technical difficulties such as long reaction times, complex preparation steps, difficulty controlling monodispersity, poor batch-to-batch stability, and inadequate large-scale production. Furthermore, the particle sizes of currently published synthesis processes, both domestically and internationally, are generally less than 10 μm, with variable particle size and dispersibility. The complex operations preclude direct application in large-scale industrial production. Summary of the Invention

[0007] In response to the above technical problems, the purpose of the present invention is to provide a monodisperse polymer porous microsphere and a preparation method thereof. The present invention provides a new method for the preparation of monodisperse polymer porous microspheres, which can control the size of the cross-linked spheres after swelling and polymerization by adjusting the size of the seed microspheres. Its advantage is that it can effectively reduce the generation of secondary small particles, thereby improving the uniformity of the microspheres after swelling and polymerization, and achieving the required requirements of monodisperse microspheres. At the same time, different porogens that can be selected when the microspheres swell change the internal pore structure of the microspheres to change the porosity, pore size, specific surface area, etc. of the microspheres, so that the microspheres can be bonded with more functional groups and increase the adsorption capacity.

[0008] In a first aspect, the present invention provides a method for preparing monodisperse polymer porous microsphere fillers, comprising the following steps:

[0009] Step S1, soaking and swelling the polystyrene seeds: adding an emulsifier, an aqueous solution of sodium dodecyl sulfate, a porogen, a swelling agent, dibutyl phthalate, a monomer styrene, a crosslinking agent, divinylbenzene, and an initiator, benzoyl peroxide, to a reaction vessel under stirring, followed by ultrasonic emulsification at below 25° C. for 30 to 60 minutes, and finally adding non-porous, non-crosslinked polystyrene microsphere seeds to the mixed system and swelling for 12 to 24 hours;

[0010] Step S2, heating and curing the swollen microspheres: adding a stabilizer polyvinyl pyrrolidone aqueous solution to the reaction vessel of step S1, heating to 65° C. to 80° C., reacting for 10 to 24 hours, washing, filtering, and drying the resulting product to obtain monodisperse polymer porous microspheres.

[0011] Preferably, the porogen is any one or more of toluene, acetonitrile, dichloromethane, 2-ethylhexanoic acid, n-heptane or trimethylbenzene. More preferably, the porogen is toluene and n-heptane, or toluene and 2-ethylhexanoic acid.

[0012] More preferably, in step S1, the mass of divinylbenzene is 1 to 3 times the mass of styrene, and the amount of the porogen is 0.5 to 2 times the total mass of styrene and divinylbenzene.

[0013] More preferably, in step S1, the mass fraction of the sodium dodecyl sulfate aqueous solution is 4%, and its amount is 4 to 8 times the total mass of styrene and divinylbenzene, the mass of the swelling agent is 0.5 to 2 times the total mass of styrene and divinylbenzene, and the mass of the initiator is 2% to 6% of the total mass of styrene and divinylbenzene.

[0014] Preferably, the stirring condition in step S1 is mechanical stirring at 200 to 400 rpm.

[0015] Preferably, in step S1, the particle size of the non-porous non-cross-linked polystyrene microsphere seeds is 3 μm to 8 μm, the particle size span is ≤0.60, and the added mass is 4% to 8% of the total mass of styrene and divinylbenzene.

[0016] Preferably, in step S2, the concentration of the polyvinyl pyrrolidone aqueous solution is 3% to 8%, and its mass is 4 to 8 times the total mass of styrene and divinylbenzene.

[0017] Preferably, in step S2, the specific conditions for centrifugation washing and drying of the product are: the obtained product is filtered, washed with tetrahydrofuran, methanol, and deionized water 2 to 3 times each, the drying temperature is 40° C. to 80° C., and the drying time is 6 h to 20 h.

[0018] In a second aspect, the present invention provides monodisperse polymer porous microspheres prepared by the above method. The monodisperse polymer porous microspheres have a specific surface area of ≥400 m2 / g, an average pore size distribution of 3 nm to 20 nm, a particle size of 10 μm to 20 μm, and a particle size span of ≤0.65.

[0019] Compared with the prior art, the present invention has at least the following beneficial effects:

[0020] The method involves two steps: the first involves ultrasonically emulsifying and swelling the seed microspheres with a stabilizer, porogen, swelling agent, monomer styrene, and crosslinker divinylbenzene, until swelling equilibrium is reached. The second step involves heating the styrene and divinylbenzene to polymerize, yielding larger polymer microspheres. This one-step swelling method produces uniform microsphere size after polymerization. The method is simple to operate, exhibits excellent process stability and reproducibility, and is therefore well-suited for industrial production. The resulting microspheres can be used in a wide range of applications.

[0021] The present invention regulates the size of the cross-linked microspheres after swelling and polymerization by adjusting the size of the seed microspheres, effectively reducing the generation of small secondary particles and improving the uniformity of the microspheres after swelling and polymerization, achieving the desired monodisperse microspheres. Furthermore, different porogens can be selected during the swelling of the microspheres to change the internal pore structure of the microspheres, thereby varying the pore size, specific surface area, and other factors of the microspheres. This allows the microspheres to bond with more functional groups, thereby increasing their adsorption capacity. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 This is an optical microscope image of the monodisperse polymer porous microspheres prepared in Example 1;

[0023] Figure 2 This is a scanning electron micrograph of the monodisperse polymer porous microspheres prepared in Example 1;

[0024] Figure 3 This is a particle size distribution diagram of the monodisperse polymer porous microspheres prepared in Example 1;

[0025] Figure 4 This is the pore size distribution diagram of the dispersed polymer porous microspheres prepared in Example 1. DETAILED DESCRIPTION

[0026] The technical solution of the present invention will be further described below with reference to the accompanying drawings and through specific embodiments. However, the following examples are merely simplified examples of the present invention and do not represent or limit the scope of protection of the present invention. The scope of protection of the present invention shall be subject to the claims.

[0027] Unless otherwise specified, the raw materials and materials used in the examples of the present invention were purchased through general commercial channels.

[0028] The sources of the raw materials, materials and instruments involved in the following examples and comparative examples are as follows:

[0029] Non-porous non-cross-linked polystyrene microsphere seeds were purchased from Suzhou Nano Micro Technology Co., Ltd.

[0030] Scanning electron microscope, model is German ZEISS Sigma 300;

[0031] Laser particle size distribution analyzer, model Bettersize 2600 (wet method);

[0032] BET test equipment, model is American Micromeritics ASAP 2460.

[0033] <Example 1>

[0034] This embodiment provides a monodisperse polymer porous microsphere and a preparation method thereof.

[0035] Step S1, soaking and swelling polystyrene seeds: turning on mechanical stirring at 250 rpm, adding 100 g of 4% sodium dodecyl sulfate aqueous solution to the reaction vessel, adding 5 g of toluene, 10 g of n-heptane, 10 g of dibutyl phthalate, then adding 5 g of styrene, 10 g of divinylbenzene, and 0.4 g of benzoyl peroxide, and ultrasonically emulsifying at below 25° C. for 30 min, finally adding 1 g of non-porous non-cross-linked polystyrene microsphere seeds with a particle size of 5.0 μm to the reaction system, and continuing swelling for 24 h;

[0036] Step S2: Curing the swollen microspheres by heating: 80 ml of a 4% aqueous solution of polyvinyl pyrrolidone was added to the reaction vessel, condensation water was removed, the temperature was raised to 70°C, and the reaction was continued for 16 hours. The resulting product was filtered, washed with tetrahydrofuran, methanol, and deionized water 2 to 3 times each, and dried at 60°C for 16 hours to obtain monodisperse porous polymer microspheres.

[0037] <Example 2>

[0038] This embodiment provides a monodisperse polymer porous microsphere and a preparation method thereof.

[0039] Step S1, soaking and swelling polystyrene seeds: turning on mechanical stirring at 250 rpm, adding 100 g of a 4% aqueous solution of sodium dodecyl sulfate, 5 g of toluene, 10 g of 2-ethylhexanoic acid, 10 g of dibutyl phthalate, 5 g of styrene, 10 g of divinylbenzene, and 0.4 g of benzoyl peroxide to a reaction vessel, and ultrasonically emulsifying at below 25° C. for 30 min, finally adding 1 g of non-porous, non-cross-linked polystyrene microsphere seeds with a particle size of 5.0 μm into the reaction system, and continuing swelling for 24 h;

[0040] Step S2: Curing the swollen microspheres by heating: 80 ml of a 4% aqueous solution of polyvinyl pyrrolidone was added to the reaction vessel, condensation water was removed, the temperature was raised to 70°C, and the reaction was continued for 16 hours. The resulting product was filtered, washed with tetrahydrofuran, methanol, and deionized water 2 to 3 times each, and dried at 60°C for 16 hours to obtain monodisperse porous polymer microspheres.

[0041] <Example 3>

[0042] This embodiment provides a monodisperse polymer porous microsphere and a preparation method thereof.

[0043] Step S1, soaking and swelling polystyrene seeds: turning on mechanical stirring at 250 rpm, adding 100 g of a 4% aqueous solution of sodium dodecyl sulfate, 15 g of toluene, 5 g of n-heptane, 10 g of dibutyl phthalate, 5 g of styrene, 10 g of divinylbenzene, and 0.4 g of benzoyl peroxide to a reaction vessel, and ultrasonically emulsifying at below 25° C. for 30 min, finally adding 1 g of non-porous non-cross-linked polystyrene microsphere seeds with a particle size of 5.0 μm into the reaction system, and continuing swelling for 24 h;

[0044] Step S2: Curing the swollen microspheres by heating: 80 ml of a 4% aqueous solution of polyvinyl pyrrolidone was added to the reaction vessel, condensation water was removed, the temperature was raised to 70°C, and the reaction was continued for 16 hours. The resulting product was filtered, washed with tetrahydrofuran, methanol, and deionized water 2 to 3 times each, and dried at 60°C for 16 hours to obtain monodisperse porous polymer microspheres.

[0045] <Example 4>

[0046] Step S1, soaking and swelling polystyrene seeds: turning on mechanical stirring at 250 rpm, adding 100 g of a 4% aqueous solution of sodium dodecyl sulfate, 5 g of toluene, 10 g of n-heptane, 10 g of dibutyl phthalate, 5 g of styrene, 10 g of divinylbenzene, and 0.4 g of benzoyl peroxide to a reaction vessel, and ultrasonically emulsifying at below 25° C. for 30 min, finally adding 1 g of non-porous non-cross-linked polystyrene microsphere seeds with a particle size of 3.0 μm into the reaction system, and continuing swelling for 24 h;

[0047] Step S2: Curing the swollen microspheres by heating: 80 ml of a 4% aqueous solution of polyvinyl pyrrolidone was added to the reaction vessel, condensation water was removed, the temperature was raised to 70°C, and the reaction was continued for 16 hours. The resulting product was filtered, washed with tetrahydrofuran, methanol, and deionized water 2 to 3 times each, and dried at 60°C for 16 hours to obtain monodisperse porous polymer microspheres.

[0048] <Example 5>

[0049] Step S1, soaking and swelling polystyrene seeds: turning on mechanical stirring at 250 rpm, adding 100 g of a 4% aqueous solution of sodium dodecyl sulfate, 5 g of toluene, 10 g of n-heptane, 10 g of dibutyl phthalate, 5 g of styrene, 10 g of divinylbenzene, and 0.4 g of benzoyl peroxide to a reaction vessel, and ultrasonically emulsifying at below 25° C. for 30 min, finally adding 1 g of non-porous non-cross-linked polystyrene microsphere seeds with a particle size of 6.2 μm into the reaction system, and continuing swelling for 24 h;

[0050] Step S2: Curing the swollen microspheres by heating: 80 ml of a 4% aqueous solution of polyvinyl pyrrolidone was added to the reaction vessel, condensation water was removed, the temperature was raised to 70°C, and the reaction was continued for 16 hours. The resulting product was filtered, washed with tetrahydrofuran, methanol, and deionized water 2 to 3 times each, and dried at 60°C for 16 hours to obtain monodisperse porous polymer microspheres.

[0051] Comparative Example 1

[0052] Step S1, soaking and swelling polystyrene seeds: turning on mechanical stirring at 250 rpm, adding 100 g of a 4% aqueous solution of sodium dodecyl sulfate, 5 g of toluene, 10 g of n-heptane, 10 g of dibutyl phthalate, 5 g of styrene, 10 g of divinylbenzene, and 0.2 g of benzoyl peroxide to a reaction vessel, and ultrasonically emulsifying at below 25° C. for 30 min, finally adding 1 g of non-porous non-cross-linked polystyrene microsphere seeds with a particle size of 5.0 μm into the reaction system, and continuing swelling for 24 h;

[0053] Step S2: Curing the swollen microspheres by heating: 80 ml of a 4% aqueous solution of polyvinyl pyrrolidone was added to the reaction vessel, condensation water was removed, the temperature was raised to 70°C, and the reaction was continued for 16 hours. The resulting product was filtered, washed with tetrahydrofuran, methanol, and deionized water 2 to 3 times each, and dried at 60°C for 16 hours to obtain monodisperse porous polymer microspheres.

[0054] Comparative Example 2

[0055] Step S1, soaking and swelling polystyrene seeds: start mechanical stirring at 250 rpm, add 50 g of 4% sodium dodecyl sulfate aqueous solution into the reaction vessel, add 5 g of toluene, 10 g of n-heptane, 10 g of dibutyl phthalate, then add 5 g of styrene, 10 g of divinylbenzene, and 0.4 g of benzoyl peroxide, and ultrasonically emulsify at below 25° C. for 30 min. Finally, add 1 g of non-porous non-cross-linked polystyrene microsphere seeds with a particle size of 5.0 μm into the reaction system, and continue swelling for 24 h;

[0056] Step S2: Curing the swollen microspheres by heating: 80 ml of a 4% aqueous solution of polyvinyl pyrrolidone was added to the reaction vessel, condensation water was removed, the temperature was raised to 70°C, and the reaction was continued for 16 hours. The resulting product was filtered, washed with tetrahydrofuran, methanol, and deionized water 2 to 3 times each, and dried at 60°C for 16 hours to obtain monodisperse porous polymer microspheres.

[0057] <Test Example 1>

[0058] The monodisperse polymer porous microspheres prepared in Example 1 were tested using an optical microscope and a scanning electron microscope. Figure 1 、 Figure 2 .

[0059] from Figure 1 It can be seen that the microspheres have uniform particle size and good dispersion.

[0060] from Figure 2 It can be seen that the surface of the microspheres presents a rough porous structure.

[0061] <Test Example 2>

[0062] The monodisperse polymer porous microspheres prepared in the examples and comparative examples were tested using a Bettersize 2600 laser particle size distribution analyzer (wet method) and a BET test equipment model of Micromeritics ASAP 2460 from the United States. The particle size and BET data are shown in Table 1 below. The particle size distribution and pore size distribution of the dispersed polymer porous microspheres of Example 1 are selected as representatives, and the specific details are shown in Table 1. Figure 3 、 Figure 4 .

[0063] Table 1. Particle size and BET data of prepared monodisperse polymer porous microspheres

[0064]

[0065] As shown in Table 1, a comparison of Examples 1, 2, and 3 shows that changing the type or amount of the porogen significantly changes the average pore diameter and specific surface area. A comparison of Examples 1, 3, and 4 shows that changing the particle size of the non-porous, non-crosslinked seed microspheres changes the particle size accordingly. In Comparative Example 1, the amount of initiator used exceeded the range of 2% to 6% of the total mass of styrene and divinylbenzene compared to Example 1, resulting in a wider particle size distribution and poorer dispersibility of the microspheres. In Comparative Example 2, the amount of the emulsifier, sodium lauryl sulfate aqueous solution, exceeded the range of 4 to 8 times the total mass of styrene and divinylbenzene compared to Example 1, also resulting in a wider particle size distribution and poorer dispersibility of the microspheres.

[0066] Figure 3 The results show that the D50 particle size of the monodisperse polymer porous microspheres prepared in Example 1 is 13.17 μm, and the particle size span is 0.509. Figure 4 The results show that the pore size distribution of the monodisperse polymer porous microspheres prepared in Example 1 is relatively concentrated, and the specific surface area is 518.6 m 2 / g, and the average adsorption pore diameter is 8.95nm.

[0067] The applicant declares that the above is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily thought of by those skilled in the art within the technical scope disclosed by the present invention fall within the protection scope and disclosure scope of the present invention.

Claims

1. A method for preparing monodisperse polymer porous microspheres, characterized in that: The following steps are involved: Step S1, soaking and swelling the polystyrene seeds: adding an emulsifier, an aqueous solution of sodium dodecyl sulfate, a porogen, a swelling agent, dibutyl phthalate, a monomer styrene, a crosslinking agent, divinylbenzene, and an initiator, benzoyl peroxide, to a reaction vessel under stirring, followed by ultrasonic emulsification at below 25° C. for 30 to 60 minutes, and finally adding non-porous, non-crosslinked polystyrene microsphere seeds to the mixed system and swelling for 12 to 24 hours; Step S2, heating and curing the swollen microspheres: adding a stabilizer polyvinyl pyrrolidone aqueous solution to the reaction vessel of step S1, heating to 65° C. to 80° C., reacting for 10 to 24 hours, washing, filtering, and drying the resulting product to obtain monodisperse polymer porous microspheres.

2. The method for preparing monodisperse polymer porous microspheres according to claim 1, wherein: The porogen is any one or more of toluene, acetonitrile, dichloromethane, 2-ethylhexanoic acid, n-heptane or trimethylbenzene.

3. The method for preparing monodisperse polymer porous microspheres according to claim 2, wherein: In step S1, the mass of the divinylbenzene is 1 to 3 times the mass of the styrene, and the amount of the porogen is 0.5 to 2 times the total mass of styrene and divinylbenzene.

4. The method for preparing monodisperse polymer porous microspheres according to claim 3, wherein: The porogen is toluene and n-heptane, or toluene and 2-ethylhexanoic acid.

5. The method for preparing monodisperse polymer porous microspheres according to claim 3, wherein: In step S1, the mass fraction of the sodium dodecyl sulfate aqueous solution is 4%, and its usage is 4 to 8 times the total mass of styrene and divinylbenzene, the mass of the swelling agent is 0.5 to 2 times the total mass of styrene and divinylbenzene, and the mass of the initiator is 2% to 6% of the total mass of styrene and divinylbenzene.

6. The method for preparing monodisperse polymer porous microspheres according to claim 3, wherein: In step S1, the particle size of the non-porous non-cross-linked polystyrene microsphere seeds is 3 μm to 8 μm, the particle size span is ≤0.60, and the added mass is 4% to 8% of the total mass of styrene and divinylbenzene.

7. The method for preparing monodisperse polymer porous microspheres according to claim 3, wherein: In step S2, the concentration of the polyvinyl pyrrolidone aqueous solution is 3% to 8%, and its mass is 4 to 8 times the total mass of styrene and divinylbenzene.

8. The method for preparing monodisperse polymer porous microspheres according to claim 1, wherein: The stirring condition in step S1 is mechanical stirring at 200 to 400 rpm; in step S2, the specific conditions for centrifugal washing and drying the product are: the obtained product is filtered, washed with tetrahydrofuran, methanol, and deionized water 2 to 3 times each, the drying temperature is 40° C. to 80° C., and the drying time is 6 h to 20 h.

9. A monodisperse polymer porous microsphere, characterized in that: The monodisperse polymer porous microspheres are prepared by the preparation method according to any one of claims 1 to 8.

10. The monodisperse polymer porous microspheres according to claim 9, wherein The specific surface area of the monodisperse polymer porous microspheres is ≥400m 2 / g, average pore size distribution is 3nm~20nm, particle size is 10μm~20μm, and particle size span is ≤0.65.

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