Preparation method and application of low-molecular-weight seed microspheres and large-particle-size microspheres of low-molecular-weight seed microspheres

Abstract

The invention relates to the technical field of polymer microspheres, in particular to a preparation method and application of low-molecular-weight seed microspheres and large-particle-size microspheres of the low-molecular-weight seed microspheres. The low-molecular-weight microspheres are seed microspheres with the D90 particle size of 100 nm-7 microns and in a rapid growth period, compared with seed microspheres prepared in the prior art, the low-molecular-weight microspheres have the advantages of being low in molecular weight, wide in distribution and not prone to agglomeration, the preparation process is simple, time is saved, preparation of large-particle-size microspheres is facilitated, and meanwhile the low-molecular-weight microspheres are suitable for large-scale production.

Description

Technical Field

[0001] The invention relates to the technical field of polymer microspheres, and in particular to a preparation method and application of low molecular weight seed microspheres and large particle size microspheres thereof. Background Art

[0002] Large-diameter polymer microspheres have the advantages of large specific surface area and strong adsorption. They have good application prospects in standard measurement, chromatographic column packing, pharmaceutical engineering and biochemical engineering. Large-diameter polymer microspheres are generally synthesized by seed swelling polymerization, and the key step of seed swelling polymerization is to synthesize seed microspheres that are conducive to swelling.

[0003] The existing synthesis method generally uses emulsion polymerization or dispersion polymerization to synthesize monodisperse polymer microspheres, then mixes a chain transfer agent with the monomer, swells the synthesized monodisperse polymer microspheres and then polymerizes them to form seed microspheres containing low molecular weight, and then uses the seed microspheres to swell and polymerize to prepare large-particle-size polymer microspheres. Although this method can be used to prepare large-particle-size polymer microspheres, the synthesis process is cumbersome and time-consuming, and the synthesized low-molecular-weight polymer microspheres are easy to agglomerate, requiring precise control of the synthesis conditions, which is not conducive to subsequent seed swelling polymerization. Summary of the invention

[0004] In view of this, the present invention provides a preparation method and application of low molecular weight seed microspheres and large particle size microspheres. The low molecular weight microspheres are not easy to agglomerate, which is conducive to the preparation of large particle size microspheres. At the same time, the preparation process is simple, time-saving, and suitable for large-scale production.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0006] Application of low molecular weight seed microspheres in the preparation of large particle size microspheres; the low molecular weight seed microspheres are seed microspheres in a rapid growth stage with a D90 particle size of 100 nm to 7 μm;

[0007] The matrix of the low molecular weight seed microspheres is at least one of polystyrene, polyglycidyl methacrylate or polymethyl methacrylate.

[0008] In the above application, the low molecular weight seed microspheres are prepared by dispersion polymerization or emulsion polymerization; the polymerization time is 30 to 120 minutes.

[0009] The present invention unexpectedly discovered that when seed microspheres are prepared by conventional dispersion polymerization or emulsion polymerization in the art, low molecular weight seed microspheres in a rapid growth period obtained with a polymerization reaction time between 30 and 120 minutes are in a highly swollen state, and at this time the molecular weight of the microspheres is low and the distribution is wide, and the microspheres are not easy to agglomerate. Using them as swellable seeds is more conducive to the seed swelling polymerization. At the same time, the preparation process is simple, time-saving, and suitable for large-scale production.

[0010] Specifically, the present invention provides a method for preparing the low molecular weight seed microspheres, comprising:

[0011] The monomer compound, the initiator and the dispersant are polymerized in a dispersion medium to prepare low molecular weight seed microspheres;

[0012] The polymerization reaction comprises: stirring and reacting at 65-85° C. for 30-120 minutes;

[0013] The monomer compound is at least one of styrene, glycidyl methacrylate or methyl methacrylate.

[0014] In the present invention, the polymerization reaction temperature is 65-85°C, specifically 65°C, 70°C, 75°C, 80°C, 85°C; the reaction time is 30-120min, preferably 30-90min, specifically 30min, 40min, 50min, 60min, 70min, 80min or 90min.

[0015] In the present invention, the usage ratio of the monomer compound, initiator, dispersant and dispersion medium is (25-250):(0.5-3):(0.5-20):(250-500) in terms of ml:g:g:ml. In some specific embodiments of the present invention, the usage ratio is 25:0.5:0.5:250, 250:3:20:500 or 100:1.5:2:500.

[0016] In the present invention, the initiator includes azobisisobutyronitrile and / or azobisisoheptanenitrile.

[0017] In the present invention, the dispersant includes sodium styrene sulfonate and / or polyvinyl pyrrolidone;

[0018] In the present invention, the dispersion medium includes water and / or alcohol; the alcohol includes methanol, ethanol and / or ethylene glycol; the volume ratio of water to alcohol is (0-10):(0-10). When the dispersion medium is water, the polymerization reaction is actually emulsion polymerization; when the dispersion medium is a mixed solution of water and alcohol or is all alcohol, it is dispersion polymerization. In some specific embodiments of the present invention, the dispersion medium is water and methanol in a volume ratio of 6:4.

[0019] The invention also provides low molecular weight seed microspheres prepared by the preparation method.

[0020] It has been determined that the D90 particle size of the low molecular weight seed microspheres prepared by the present invention is 100nm to 7μm. In some embodiments, styrene is used as a monomer, sodium styrene sulfonate is used as a dispersant, methanol aqueous solution is used as a dispersion medium, and azobisisobutyronitrile is used as an initiator. The D90 particle size of the low molecular weight seed microspheres prepared at different polymerization times (30min, 90min) is 200nm or 500nm respectively. In other embodiments, when styrene is used as a monomer, polyvinyl pyrrolidone is used as a dispersant, ethanol is used as a dispersion medium, and azobisisobutyronitrile is used as an initiator, the D90 particle size of the low molecular weight seed microspheres prepared according to the method of the present invention is 6μm. In other embodiments, when glycidyl methacrylate is used as a monomer, polyvinyl pyrrolidone is used as a dispersant, ethanol is used as a dispersion medium, and azobisisobutyronitrile is used as an initiator, the D90 particle size of the low molecular weight seed microspheres prepared according to the method of the present invention is 1μm.

[0021] The present invention also provides the use of low molecular weight seed microspheres prepared by the above preparation method in preparing monodisperse large particle size microspheres.

[0022] The present invention provides a method for preparing large-diameter microspheres, comprising:

[0023] The large-diameter microspheres are obtained by swelling the low-molecular-weight seed microspheres prepared by the above preparation method.

[0024] In the preparation method of large-size microspheres of the present invention, in some embodiments, the swelling is a one-step swelling (i.e., the first swelling) using a swelling agent. In other embodiments, the swelling is a two-step swelling (the first swelling and the second swelling, respectively) using a swelling agent and a monomer. The swelling conditions are 30°C, stirring at 200-400r / min for 24-48h; preferably, the first swelling condition is 30°C, stirring at 200r / min for 24h; the second swelling condition is 30°C, stirring at 400r / min for 48h.

[0025] The present invention has no particular restrictions on the specific type of swelling agent, and any solvent with a solubility parameter close to that of the low molecular weight seed microsphere polymer microsphere can be used. In the present invention, the swelling agent includes at least one of DBP (dibutyl phthalate), acetone, toluene, and 1-chlorododecane. In the present invention, the crosslinking agent is a monomer containing two vinyl groups, specifically DVB.

[0026] In some specific embodiments of the present invention, in the first swelling process, the reagents used include an emulsifier in addition to the swelling agent; in the second swelling, the reagents used may include an emulsifier and / or a cross-linking agent in addition to the monomer. The present invention has no special restrictions on the specific types of emulsifiers, and the common ionic emulsifiers and non-ionic emulsifiers in the art are all acceptable. In the present invention, the emulsifier is an ionic emulsifier SDS. Those skilled in the art may choose to add or not add a cross-linking agent based on actual conditions; the cross-linking agent is a monomer compound containing two vinyl groups, such as DVB, etc.

[0027] The invention also provides large-diameter microspheres prepared according to the preparation method.

[0028] It has been determined that the D90 particle size of the large-diameter microspheres is 1 μm to 65 μm. In some embodiments, the D90 particle size of the large-diameter microspheres prepared by the present invention is 1 μm, 3 μm, 12 μm, or 45 μm.

[0029] The present invention provides a preparation method and application of low molecular weight seed microspheres and large particle size microspheres. The low molecular weight microspheres are not easy to agglomerate, which is conducive to the preparation of large particle size microspheres. At the same time, the preparation process is simple, time-saving, and suitable for large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 The electron microscopy results of the low molecular weight seed microspheres prepared in Example 1 are shown, and the scale bar is 1 μm;

[0031] Figure 2 1 shows the microscopic observation results of the microspheres after the first swelling in Example 1;

[0032] Figure 3 The microscopic observation results of the microspheres after secondary swelling and polymerization in Example 1 are shown;

[0033] Figure 4 The electron microscopy results of the low molecular weight seed microspheres prepared in Example 2 are shown, and the scale bar is 1 μm;

[0034] Figure 5 2 shows the microscopic observation results of the microspheres after the first swelling in Example 2;

[0035] Figure 6 The GPC test spectra (molecular weight distribution width) of the swellable seeds prepared in Example 1 and Example 2 are shown. The abscissa represents the peak time during the GPC test, and the peak time reflects the molecular weight. The large molecular weight peaks first, and the small molecular weight peaks later. The ordinate is the sample concentration / absolute injection volume dwt / d (logM), which has been normalized here, and all peaks are consistent;

[0036] Figure 7The electron microscopy results of the low molecular weight seed microspheres prepared in Example 3 are shown, and the scale bar is 20 μm;

[0037] Figure 8 4 shows the microscopic observation results of the microspheres after the first swelling in Example 3;

[0038] Fig. 9 The microscopic observation results of the microspheres after secondary swelling and polymerization in Example 3 are shown;

[0039] Fig.10 The electron microscopy results of the low molecular weight seed microspheres prepared in Example 4 are shown, and the scale is 2.5 μm;

[0040] Fig.11 4 shows the microscopic observation results of the microspheres after the first swelling in Example 4;

[0041] Fig.12 The microscopic observation results of the microspheres after secondary swelling and polymerization in Example 4 are shown;

[0042] Fig.13 1 shows the microscope observation results of the first generation microspheres prepared in Comparative Example 1;

[0043] Fig.14 1 and 2 show the microscope observation results of the second-generation seed microspheres prepared in Comparative Example 1. DETAILED DESCRIPTION

[0044] The present invention provides a method for preparing low molecular weight seed microspheres and large particle size microspheres thereof and their application. Those skilled in the art can refer to the content of this article and appropriately improve the process parameters to achieve it. It is particularly important to point out that all similar substitutions and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention. The method and application of the present invention have been described through preferred embodiments, and relevant personnel can obviously modify or appropriately change and combine the method and application of this article without departing from the content, spirit and scope of the present invention to implement and apply the technology of the present invention.

[0045] The test materials used in the present invention are all common commercial products and can be purchased in the market.

[0046] The present invention will be further described below in conjunction with embodiments:

[0047] Example 1

[0048] (1) Synthesis of low molecular weight swellable seed microspheres (i.e. low molecular weight seed microspheres, referred to as PS)

[0049] 25 ml of monomer styrene, 0.5 g of initiator azobisisobutyronitrile, 0.5 g of dispersant sodium styrene sulfonate, 250 ml of dispersion medium (methanol: water = 6:4), after mixing the above reagents, heat to 75 ° C, continue stirring for 30 minutes, and obtain swellable seed microspheres PS with a particle size of 200 nm. Figure 1 .

[0050] (2) Preparation of large-size microspheres

[0051] Preparation of large-size microspheres by one-step swelling method

[0052] Weigh 1 g of the low molecular weight swellable seed microspheres PS prepared in step (1), add 120 ml of SDS aqueous solution (0.25%) to disperse PS, add 80 ml of SDS (0.25%) and 10 g of DBP, mix, and disperse by ultrasonication. Stir at 30°C and 200 r / min for 24 h to obtain swollen microspheres. The results are shown in Figure 2 .

[0053] The results showed that the microspheres after swelling were uniform in size, with a D90 particle size of 3 μm.

[0054] Preparation of large-size microspheres by two-step swelling method

[0055] Weigh 1g of PS prepared in step (1), add 120ml of SDS aqueous solution (0.25%) to disperse PS, add 80ml of SDS (0.25%) and DBP: 100g to mix, ultrasonically disperse, mix and stir for 24h, set the temperature to 30℃, 200r / min. Continue to add monomer emulsion (St: 25ml, DVB: 75ml, 0.25% SDS: 50ml), continue to stir for 48h after mixing, add 200ml of water during the process, set the temperature to 30℃, 400r / min, and obtain large-size microspheres after swelling. The results are shown in Figure 3 .

[0056] The results showed that the D90 particle size of the swollen microspheres was 12 μm.

[0057] Example 2

[0058] (1) Synthesis of low molecular weight swellable seed microspheres (PS): 25 ml of styrene monomer, 0.5 g of initiator azobisisobutyronitrile, 0.5 g of dispersant sodium styrene sulfonate, and 250 ml of dispersion medium (methanol: water = 6:4). The above reagents were mixed and heated to 75°C and stirred for 90 min to obtain swellable seed microspheres PS with a particle size of 500 nm (see Figure 4 ), scale bar is 1 μm

[0059] (2) Swelling the low molecular weight swellable seed microspheres (PS): Weigh 1 g of PS obtained in step (1), disperse the PS with 120 ml of SDS aqueous solution (0.25%), add 80 ml of SDS (0.25%) and DBP: 10 g, mix, and ultrasonically disperse. Mix and stir for 24 h at 30 °C and 200 r / min to obtain swollen microspheres with a size of 1 μm (see Figure 5 ).

[0060] The low molecular weight seed microspheres obtained in step (1) of Example 1 and step (1) of Example 2 were subjected to GPC test. The test spectra are shown in Figure 6 The results show that the low molecular weight seed microspheres prepared by the present invention have a wide molecular weight distribution.

[0061] Example 3

[0062] (1) Synthesis of low molecular weight swellable seed microspheres (PS): 250 ml of styrene monomer, 3 g of initiator azobisisobutyronitrile, 20 g of dispersant polyvinyl pyrrolidone, and 500 ml of dispersion medium (ethanol). The above reagents were mixed and heated to 75°C and stirred for 90 min to obtain swellable seed microspheres PS ( Figure 7 ), scale bar 20 μm.

[0063] (2) Swelling of low molecular weight swellable seed microspheres to prepare large particle size microspheres

[0064] One-step swelling of swellable seed microspheres

[0065] Weigh 1g of PS from step (1), disperse PS with 120ml SDS aqueous solution (0.25%), add 80ml SDS (0.25%) and DBP: 100g, mix, ultrasonically disperse, mix and stir for 24h, set the temperature to 30℃, 200r / min. After swelling, 12μm microspheres were obtained. Figure 8 .

[0066] Two-step swelling of swellable seed microspheres

[0067] Weigh 1g of PS from step (1), disperse PS with 120ml SDS aqueous solution (0.25%), add 80ml SDS (0.25%) and mix with 100g DBP, disperse by ultrasonic, mix and stir for 24h, set the temperature at 30℃, 200r / min. Continue to add monomer emulsion (St: 25ml, DVB: 75ml, 0.25% SDS: 50ml), continue stirring for 48h after mixing, add 200ml water during the process, set the temperature at 30℃, 400r / min, and obtain 45μm microspheres after swelling, see Fig. 9 .

[0068] Example 4

[0069] (1) Synthesis of low molecular weight swellable seed microspheres PGMA: monomer glycidyl methacrylate 100 ml, initiator azobisisobutyronitrile 1.5 g, dispersant polyvinyl pyrrolidone 2 g, dispersion medium 500 ml (ethanol), after mixing the above reagents, heating to 75 ° C, stirring for 60 min, to obtain swellable seed microspheres PGMA with a particle size of 1 μm, see Fig.10 , scale bar 5μm.

[0070] (2) Swelling of PGMA swellable seed microspheres

[0071] One-step swelling of PGMA swellable seed microspheres

[0072] Weigh 1 g of PGMA obtained in step (1), disperse PGMA with 120 ml of SDS aqueous solution (0.25%), add 80 ml of SDS (0.25%) and DBP: 10 g, mix, ultrasonically disperse, mix and stir for 24 h, set the temperature to 30 ° C, 200 r / min, and obtain 5 μm microspheres after swelling. Fig.11 .

[0073] Two-step swelling of swellable seed microspheres PGMA

[0074] Weigh 1g of PGMA obtained in step (1), disperse PGMA with 120ml SDS aqueous solution (0.25%), add 80ml SDS (0.25%) and mix with 100g DBP, disperse by ultrasonic, mix and stir for 24h, set the temperature at 30℃, 200r / min. Continue to add monomer emulsion (GMA: 25ml, DVB: 75ml, 0.25% SDS: 50ml), continue to stir for 48h after mixing, add 200ml water in the process, set the temperature at 30℃, 400r / min, and obtain 40μm microspheres after swelling. Fig.12 .

[0075] Comparative Example 1

[0076] (1) Synthesis of high molecular weight first-generation seed: 900 ml of styrene monomer, 15 g of azobisisobutyronitrile initiator, 95 g of polyvinyl pyrrolidone dispersant, and 2500 ml of ethanol dispersant. Mix the above reagents and heat to 75°C. Continue stirring for 8 h to obtain first-generation seed microspheres with a particle size of 5 μm. Fig.13 .

[0077] (2) Synthesis of low molecular weight second generation seeds: 5 g of the first generation seeds were dispersed in a 0.1 w / w% SDS aqueous solution, and a mixture of styrene (10 ml) and carbon tetrabromide (1 g) was added. The mixture was stirred at room temperature and 200 r / min for 24 h. A mixture of 0.25 g of azobisisobutyronitrile and 2.5 ml of dichloroethane was added. The mixture was stirred for 2 h and then heated to 60°C and reacted for 8 h. The product was washed with ethanol three times to obtain second generation seed microspheres. Fig.14 .

[0078] The results show that the low molecular weight polymer microspheres synthesized by the traditional method (Comparative Example 1) are easily agglomerated and cannot be used for subsequent seed swelling polymerization.

[0079] The above are only preferred embodiments of the present invention. It should be pointed out that, for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. Application of low molecular weight seed microspheres in the preparation of large particle size microspheres; the low molecular weight seed microspheres have a D90 particle size of 100 nm to 7 μm and are in a rapid growth stage; The monomer of the low molecular weight seed microspheres includes at least one of styrene, glycidyl methacrylate or methyl methacrylate.

2. The use according to claim 1, characterized in that: The low molecular weight seed microspheres are prepared by dispersion polymerization or emulsion polymerization; the polymerization time is 30 to 120 minutes.

3. A method for preparing low molecular weight seed microspheres, characterized in that: include: The monomer compound, the initiator and the dispersant are polymerized in a dispersion medium to obtain low molecular weight seed microspheres; The polymerization reaction comprises: stirring and reacting at 65-85° C. for 30-120 minutes; The monomer compound is at least one of styrene, glycidyl methacrylate or methyl methacrylate.

4. The preparation method according to claim 3, characterized in that: The polymerization reaction is as follows: stirring the reaction at 75° C. for 30 to 90 minutes.

5. The preparation method according to claim 3, characterized in that: Calculated in ml:g:g:ml, the usage ratio of the monomer compound, initiator, dispersant and dispersion medium is (25-250):(0.5-3):(0.5-20):(250-500).

6. The preparation method according to claim 3, characterized in that: The initiator includes azobisisobutyronitrile and / or azobisisoheptanenitrile; The dispersant includes sodium styrene sulfonate and / or polyvinyl pyrrolidone; The dispersion medium includes water and alcohol; the volume ratio of water to alcohol is (0-10): (0-10).

7. Low molecular weight seed microspheres prepared by the preparation method according to any one of claims 3 to 6.

8. The low molecular weight seed microspheres according to claim 7, characterized in that: Its D90 particle size is 100nm~7μm.

9. Use of the low molecular weight seed microspheres prepared by the preparation method according to any one of claims 3 to 6 or the low molecular weight seed microspheres according to any one of claims 7 to 8 in the preparation of monodisperse large-size microspheres.

10. A method for preparing large-size microspheres, characterized in that: include: The large-diameter microspheres are obtained by swelling the low-molecular-weight seed microspheres prepared by the preparation method according to any one of claims 3 to 6 or the low-molecular-weight seed microspheres according to any one of claims 7 to 8.

11. The preparation method according to claim 10, characterized in that: The swelling is performed by using a swelling agent for one step swelling or by using a swelling agent and a monomer in sequence for two steps swelling; the swelling conditions are: 30° C., stirring at 200 to 400 r / min for 24 to 48 hours; The swelling agent includes at least one of DBP, acetone, toluene and 1-chlorododecane; The monomer includes at least one of styrene, glycidyl methacrylate or methyl methacrylate.

12. Large-diameter microspheres prepared by the preparation method according to any one of claims 10 to 12.

13. The large-diameter microspheres according to claim 12, characterized in that: Its D90 particle size is 1μ~65μm.

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