Method for preparing PGMA porous microspheres through photo-initiation and obtained material

Abstract

The preparation method comprises the following steps: preparing a water phase, preparing an oil phase, pouring the oil phase into the water phase, and carrying out photo-initiation to prepare the PGMA porous microspheres. The preparation method comprises the following steps: taking PGMA as a raw material, shearing into a suspension pre-polymerization solution, diluting the suspension pre-polymerization solution to a quartz glass tube, carrying out illumination polymerization by using two groups of ultraviolet lamps, continuously and stably conveying the suspension pre-polymerization solution to the quartz glass tube, and collecting the reacted suspension to obtain the PGMA porous microspheres. The preparation method is continuous and controllable, liquid drops can rapidly crumb, meanwhile, the surface tension change is small, the stability of the size and the structure of the PGMA microspheres in the technological synthesis process is improved, the product particle size distribution is narrow, meanwhile, the requirements for equipment, sites and the like are low, and good economical efficiency and stability are shown.

Description

Technical Field

[0001] The invention belongs to the field of porous microsphere preparation, and particularly relates to a method for preparing PGMA porous microspheres by light initiation and the obtained material. Background Art

[0002] As a material with high specific surface area, good biocompatibility and adjustable pore structure, porous microspheres are widely used in biomedicine, environmental protection, chemical industry and other fields. Among them, PGMA porous microspheres have extremely high application value in drug carriers, biosensors, catalyst carriers, etc. due to their unique chemical properties and physical structure.

[0003] At present, the preparation methods of porous microspheres mainly include emulsion polymerization, suspension polymerization, template synthesis, etc. These methods have achieved the preparation of PGMA porous microspheres to a certain extent, but there are the following problems: the synthesis process is complicated, the operation steps are cumbersome, the production cycle is long, and it is very common in the prior art to keep the reaction warm for more than 10 hours; the particle size and pore structure are difficult to accurately control, resulting in unstable product performance, especially in reactors with poor mass transfer and heat transfer effects, the microspheres prepared are often wider in particle size and low in product yield, and more seriously, it may even cause the base balls to stick together, making it difficult to clean or even unusable; the synthesis is mostly done in intermittent reactors, and the batch difference and product stability are difficult to accurately control, and a large number of post-processing processes are required for regulation, which is costly. Summary of the invention

[0004] Purpose of the invention: The purpose of the present invention is to provide a method for preparing PGMA porous microspheres by photoinitiation, which utilizes ultraviolet light initiation to shorten the production time, reduce the risk of untimely heat exchange, and enable continuous production; another purpose of the present invention is to provide materials obtained by the method for preparing PGMA porous microspheres by photoinitiation.

[0005] Technical solution: The method for preparing PGMA porous microspheres by light initiation of the present invention comprises the following steps:

[0006] S1. Preparation of aqueous phase: prepare aqueous phase by taking polymer surfactant, deionized water, inorganic salt and small molecule surfactant;

[0007] S2, oil phase preparation: glycidyl methacrylate, crosslinking agent, photoinitiator, and oily small molecule are used to prepare the oil phase;

[0008] S3, shearing: pouring the oil phase described in S2 into the water phase described in S1, and shearing into a suspended prepolymer liquid;

[0009] S4, dilution: diluting the suspended prepolymer solution into a quartz glass tube;

[0010] S5. Polymerization: Use 2 groups of ultraviolet lamps for light polymerization; the ultraviolet lamps are cold light source ultraviolet lamps; the first group of ultraviolet lamps are short-wave ultraviolet lamps with a wavelength of 200-300nm; the second group of ultraviolet lamps are long-wave ultraviolet lamps with a wavelength of 300-400nm.

[0011] S6, continuous feeding: continuously and stably conveying the suspended prepolymer liquid to the quartz glass tube;

[0012] S7. Material collection: collecting the suspension after the reaction to obtain PGMA porous microspheres.

[0013] Preferably, in S1, the polymer surfactant, deionized water, inorganic salt, and small molecule surfactant are stirred and dissolved uniformly in a stirred tank, and nitrogen is passed to deoxygenate for 20-60 minutes;

[0014] The polymer surfactant is at least one of polyoxyethylene, carboxymethyl cellulose, hydroxymethyl cellulose, gelatin, guar gum, and polyvinyl alcohol;

[0015] The inorganic salt is at least one of sodium chloride, sodium nitrite, sodium sulfate, potassium chloride, potassium sulfate, and ammonium sulfate;

[0016] The small molecule surfactant is sodium dodecyl sulfate or sodium dodecylbenzene sulfonate.

[0017] Preferably, in S2, glycidyl methacrylate, a crosslinking agent, a photoinitiator, and an oily small molecule are stirred and dissolved uniformly in a stirring tank;

[0018] The crosslinking agent is at least one of ethylene glycol dimethacrylate, 1,4-butanediol dimethacrylate, trimethylolpropane trimethacrylate, pentaerythritol diacrylate and pentaerythritol triacrylate;

[0019] The photoinitiator is at least one of 2-hydroxy-2-methyl-1-phenylpropanone, 1-hydroxycyclohexyl phenyl ketone, 2-methyl-2-(4-morpholinyl)-1-[4-(methylthio)phenyl]-1-propanone, and 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone;

[0020] The oily small molecule is at least one of n-hexane, n-hexanol, methyl isobutyl carbinol and n-heptane.

[0021] Preferably, in S3, the oil phase of S2 is poured into the water phase of S1, and sheared into a suspension prepolymer with a certain droplet size by a shearing device; the droplet size is selected according to the particle size of the microspheres actually prepared, which is 15-45 μm; the oil-water ratio of the suspension prepolymer is 1:2-5.

[0022] Preferably, the shearing equipment is one of a stirred tank, a ball mill and a shearing machine.

[0023] Preferably, in S4, the sheared suspended prepolymer and deionized water are pumped into a quartz glass tube with a three-way interface and a transmittance of 80%-92% at a mass ratio of 1:2-4 by a delivery pump.

[0024] Preferably, the flow rate of the delivery pump described in S4 is 2-30 mL / min.

[0025] Preferably, there are 2 groups of quartz glass tubes in S4, with 2-8 tubes in each group, the tubes are connected by hoses, and the groups are separated by boxes; the suspended prepolymer liquid passes through the 2 groups of quartz glass tubes in sequence.

[0026] Preferably, the two groups of ultraviolet lamps in S5 are respectively arranged on the periphery of two groups of quartz glass tubes; the suspended prepolymer liquid first passes through the quartz glass tubes in the first group of ultraviolet lamps, and then passes through the quartz glass tubes in the second group of ultraviolet lamps.

[0027] Preferably, the radiation intensity of a single UV lamp is 800-1500 μW / cm 2 .

[0028] Preferably, the inner diameter of the quartz glass tube is 1-2 cm and the wall thickness is 2-3 mm; the length of a single quartz glass tube is 50-100 cm; the length of the ultraviolet lamp is consistent with that of a single quartz tube; the length of the ultraviolet lamp is 50-100 cm; the arrangement combination of the ultraviolet lamps is 2 at an angle of 180°, 3 at an angle of 120° or 4 at an angle of 90°.

[0029] Preferably, the continuous loading described in S6 requires that the material be irradiated under the two groups of ultraviolet lamps for the same length of time, and the total irradiation time is 30-60 minutes.

[0030] Preferably, in S6, the delivery pump is adjusted so that the material is continuously and stably delivered to the quartz glass tube.

[0031] Preferably, in S7, a container is used to collect the suspension after the reaction at the outlet end of the glass tube until no material flows out, thereby completing the UV-initiated polymerization of the entire PGMA porous microspheres.

[0032] The PGMA porous microspheres prepared by the method of the invention.

[0033] Beneficial effects: Compared with the prior art, the present invention has the following significant advantages: (1) This method provides a method for continuously preparing porous PGMA microspheres, the polymerization end process is stable, the product batch difference is reduced, and the prepared product has better uniformity; (2) A short-wave ultraviolet lamp is used to first promote the solidification of the droplet surface to form a stable shell, reduce the aggregation of droplets, and then a long-wave ultraviolet lamp is used to further mature the inside of the microspheres to form porous microspheres with stable structures; (3) The maximum reaction temperature is less than 40°C, and the surface tension of the system changes little, avoiding the risk of system stability deterioration caused by the heating process of the traditional intermittent reactor; (4) The equipment process is simple, the requirements for the factory building are low, and the production process is safe and controllable. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 This is a 10x microscope image of the microspheres prepared in Example 1 of the present invention;

[0035] Figure 2 Surface tension curves of PGMA system at different temperatures in Example 1 of the present invention and Comparative Example 1. DETAILED DESCRIPTION

[0036] The technical solution of the present invention is further described below in conjunction with the accompanying drawings.

[0037] Example 1

[0038] Example 1 provides a method for preparing PGMA porous microspheres by photoinitiation, comprising the following steps:

[0039] S1, water phase preparation: 1168.2g polyoxyethylene, 38.6kg deionized water, 12.5g sodium chloride, 30.4g sodium dodecyl sulfate were stirred and dissolved in a stirred tank, and nitrogen was passed through to deoxygenate for 40min; S2, oil phase preparation: 2389.3g glycidyl methacrylate, 1641.5g ethylene glycol dimethacrylate, 2013.6g 2-Hydroxy-2-methyl-1-phenylpropanone and 3601.8g of n-hexane are stirred and dissolved uniformly in a stirring kettle; S3, shearing: pouring the oil phase described in S2 into the water phase described in S1, and using a shearing machine to shear into a suspended prepolymer with a particle size of 15μm; S4, dilution: pumping the sheared suspended prepolymer and deionized water into a quartz glass tube with an inner diameter of 1.5cm and a three-way interface at a mass ratio of 1:4 through a delivery pump; S5, polymerization: turning on ultraviolet lamps with wavelengths of 254nm and 365nm outside the quartz glass tube to perform photoinitiated polymerization; S6, continuous feeding: adjusting the delivery pump so that the material is continuously and stably delivered to the quartz glass tube at a rate of 5mL / min; S7, material collection: using a container to collect the suspension after the reaction at the outlet of the glass tube until no material flows out, completing the ultraviolet light-initiated polymerization of PGMA porous microspheres with a particle size of 30μm. Figure 1This is a 10x microscope picture of the microspheres prepared in Example 1.

[0040] Example 2

[0041] Example 2 provides a method for preparing PGMA porous microspheres by photoinitiation, comprising the following steps:

[0042] S1, water phase preparation: 742.5g gelatin, 38.6kg deionized water, 14.7g sodium nitrite, 30.4g sodium dodecyl sulfate were stirred and dissolved in a stirred tank, and nitrogen was passed through to deoxygenate for 30min; S2, oil phase preparation: 2145.5g pentaerythritol diacrylate, 1641.5g ethylene glycol dimethacrylate, 2231.4g 1-Hydroxycyclohexyl phenyl ketone and 3601.8g of n-hexanol are stirred and dissolved uniformly in a stirring kettle; S3, shearing: pour the oil phase described in S2 into the water phase described in S1, and use a shearing machine to shear it into a suspended prepolymer with a particle size of 30μm; S4, dilution: pump the sheared suspended prepolymer and deionized water into a quartz glass tube with an inner diameter of 1.5cm and a three-way interface at a mass ratio of 1:3 through a delivery pump; S5, polymerization: turn on the ultraviolet lamp with a wavelength of 254nm and 365nm outside the quartz glass tube to perform photoinitiated polymerization; S6, continuous feeding: adjust the delivery pump to continuously and stably deliver the material to the quartz glass tube at a rate of 10mL / min; S7, material collection: use a container to collect the suspension after the reaction at the outlet of the glass tube until no material flows out, and the ultraviolet light-initiated polymerization of PGMA porous microspheres with a particle size of 60μm is completed.

[0043] Example 3

[0044] Example 3 provides a method for preparing PGMA porous microspheres by photoinitiation, comprising the following steps:

[0045] S1, water phase preparation: 603.8g carboxymethyl cellulose, 38.6kg deionized water, 30.3g sodium chloride, 30.4g sodium dodecyl sulfate were stirred and dissolved in a stirred tank, and nitrogen was passed through to deoxygenate for 40min; S2, oil phase preparation: 2389.3g glycidyl methacrylate, 1641.5g ethylene glycol dimethacrylate, 2635.6g 2-Hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone and 3601.8g of n-heptane are stirred and dissolved uniformly in a stirring kettle; S3, shearing: pouring the oil phase described in S2 into the water phase described in S1, and using a shearing machine to shear into a suspended prepolymer with a particle size of 45μm; S4, dilution: pumping the sheared suspended prepolymer and deionized water into a quartz glass tube with an inner diameter of 1.5cm and a three-way interface at a mass ratio of 1:2 through a delivery pump; S5, polymerization: turning on ultraviolet lamps with wavelengths of 254nm and 365nm around the quartz glass tube to perform photoinitiated polymerization; S6, continuous feeding: adjusting the delivery pump so that the material is continuously and stably delivered to the quartz glass tube at a rate of 20mL / min; S7, material collection: using a container to collect the suspension after the reaction at the outlet of the glass tube until no material flows out, completing the ultraviolet light-initiated polymerization of PGMA porous microspheres with a particle size of 90μm.

[0046] Comparative Example 1

[0047] Comparative Example 1 provides a method for preparing PGMA porous microspheres by photoinitiation, which is different from Example 1 in that the polymerization method is different, and the following steps are performed in sequence:

[0048] S1, water phase preparation: 1168.2g polyoxyethylene, 61.7kg deionized water, 12.5g sodium chloride, 30.4g sodium dodecyl sulfate were stirred and dissolved uniformly in a stirred tank, and nitrogen was passed through to deoxygenate for 30min; S2, oil phase preparation: 2389.3g glycidyl methacrylate, 1641.5g ethylene glycol dimethacrylate, 2971.3g benzoyl peroxide, 3601.8g n-hexane were stirred and dissolved uniformly in a stirred tank ; S3, shearing: pour the oil phase described in S2 into the water phase described in S1, and use mechanical stirring to shear the average particle size of the droplets to 15μm; S4, temperature increase polymerization: raise the temperature in the reactor to 65°C through a high and low temperature integrated machine, and maintain it for 1h; S6, temperature increase aging: raise the temperature in the reactor to 75°C through a high and low temperature integrated machine, and keep it warm for 15h; S7, material collection: the material is cooled to room temperature to complete the free radical initiated polymerization of PGMA porous microspheres with a particle size of 30μm. Figure 2 Surface tension curves of the systems of Example 1 and Comparative Example 1 at different temperatures.

[0049] Comparative Example 2

[0050] Comparative Example 2 provides a method for preparing PGMA porous microspheres by light initiation, which is different from Example 1 in that the light irradiation method is different, and the following steps are performed in sequence:

[0051] S1, water phase preparation: 1168.2g polyoxyethylene, 38.6kg deionized water, 12.5g sodium chloride, 30.4g sodium dodecyl sulfate were stirred and dissolved uniformly in a stirred tank, and nitrogen was passed through to deoxygenate for 40min; S2, oil phase preparation: 2389.3g glycidyl methacrylate, 1641.5g ethylene glycol dimethacrylate, 2013.6g 2-hydroxy-2-methyl-1-phenylacetone, 3601.8g n-hexane were stirred and dissolved uniformly in a stirred tank; S3, shearing: the oil phase described in S2 was poured into the water phase described in S1, and sheared into a suspended prepolymer liquid with a particle size of 15μm by a shearing machine; S4, polymerization: the sheared suspended prepolymer liquid was directly placed under a 365nm wavelength ultraviolet lamp for 45min to complete the ultraviolet light-initiated polymerization of PGMA porous microspheres with a particle size of 30μm.

[0052] The particle size distribution of the PGMA porous microspheres obtained in Examples 1-3 and Comparative Examples 1-2 was measured by a laser particle size analyzer. The specific results are shown in Table 1.

[0053] Table 1:

[0054] project D10 D50 D90 D90 / D10 Example 1 24.45 31.06 38.15 1.56 Example 2 44.31 58.47 71.05 1.60 Example 3 68.69 92.11 115.44 1.68 Comparative Example 1 21.64 32.34 48.15 2.23 Comparative Example 2 23.17 32.26 44.52 1.92

[0055] As shown in Table 1, the PGMA porous microspheres prepared by UV-induced polymerization have a narrower particle size distribution. In addition to the short-wave stage that promotes the rapid formation of the droplet shell, Figure 2 It shows that the reaction temperature of the ultraviolet light-initiated system does not change significantly, so the surface tension of the system changes slightly, and the base balls will not coalesce during the heating process, and the particle size distribution retains the distribution state during shearing. However, when the prepolymer liquid is directly placed under the ultraviolet lamp and irradiated with a single ultraviolet lamp, the concentration of heat will still cause the droplets to coalesce, causing the particle size distribution to become wider. At the same time, the penetration ability of ultraviolet light is weakened, and further scale-up production cannot be carried out, as shown in Comparative Example 2.

Claims

1. A method for preparing PGMA porous microspheres by light initiation, characterized in that: The following steps are involved: S1. Preparation of aqueous phase: prepare aqueous phase by taking polymer surfactant, deionized water, inorganic salt and small molecule surfactant; S2, oil phase preparation: glycidyl methacrylate, crosslinking agent, photoinitiator, and oily small molecule are used to prepare the oil phase; S3, shearing: pouring the oil phase described in S2 into the water phase described in S1, and shearing into a suspended prepolymer liquid; S4, dilution: diluting the suspended prepolymer solution into a quartz glass tube; S5, polymerization: using two groups of ultraviolet lamps for light polymerization; the ultraviolet lamps are cold light source ultraviolet lamps; the first group of ultraviolet lamps are short-wave ultraviolet lamps with a wavelength of 200-300nm; the second group of ultraviolet lamps are long-wave ultraviolet lamps with a wavelength of 300-400nm; S6, continuous feeding: continuously and stably conveying the suspended prepolymer liquid to the quartz glass tube; S7. Material collection: collecting the suspension after the reaction to obtain PGMA porous microspheres.

2. The method for preparing PGMA porous microspheres by light initiation according to claim 1, characterized in that: In S1, a high molecular surfactant, deionized water, an inorganic salt, and a small molecular surfactant are stirred and dissolved uniformly in a stirring tank, and nitrogen is passed to deoxygenate for 20-60 minutes; The polymer surfactant is at least one of polyoxyethylene, carboxymethyl cellulose, hydroxymethyl cellulose, gelatin, guar gum, and polyvinyl alcohol; The inorganic salt is at least one of sodium chloride, sodium nitrite, sodium sulfate, potassium chloride, potassium sulfate, and ammonium sulfate; The small molecule surfactant is sodium dodecyl sulfate or sodium dodecylbenzene sulfonate.

3. The method for preparing PGMA porous microspheres by light initiation according to claim 1, characterized in that: In S2, glycidyl methacrylate, a crosslinking agent, a photoinitiator, and an oily small molecule are stirred and dissolved uniformly in a stirring tank; The crosslinking agent is at least one of ethylene glycol dimethacrylate, 1,4-butanediol dimethacrylate, trimethylolpropane trimethacrylate, pentaerythritol diacrylate and pentaerythritol triacrylate; The photoinitiator is at least one of 2-hydroxy-2-methyl-1-phenylpropanone, 1-hydroxycyclohexyl phenyl ketone, 2-methyl-2-(4-morpholinyl)-1-[4-(methylthio)phenyl]-1-propanone, and 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone; The oily small molecule is at least one of n-hexane, n-hexanol, methyl isobutyl carbinol and n-heptane.

4. The method for preparing PGMA porous microspheres by light initiation according to claim 1, characterized in that: In S3, the oil phase of S2 is poured into the water phase of S1, and sheared into a suspension prepolymer with a certain droplet size by a shearing device; the droplet size is selected according to the particle size of the microspheres actually prepared, which is 15-45 μm; the oil-water ratio of the suspension prepolymer is 1:2-5.

5. The method for preparing PGMA porous microspheres by light initiation according to claim 1, characterized in that: In S4, the sheared suspension prepolymer and deionized water are pumped into a quartz glass tube with a transmittance of 80%-92% and a three-way interface at a mass ratio of 1:2-4 through a delivery pump.

6. The method for preparing PGMA porous microspheres by light initiation according to claim 1, characterized in that: There are 2 groups of quartz glass tubes in S4, with 2-8 tubes in each group. The tubes are connected by hoses and the groups are separated by boxes. The suspended prepolymer liquid passes through the 2 groups of quartz glass tubes in sequence.

7. The method for preparing PGMA porous microspheres by light initiation according to claim 6, characterized in that: The two groups of ultraviolet lamps in S5 are arranged outside the two groups of quartz glass tubes respectively; the suspended prepolymer liquid first passes through the quartz glass tube in the first group of ultraviolet lamps, and then passes through the quartz glass tube in the second group of ultraviolet lamps.

8. The method for preparing PGMA porous microspheres by light initiation according to claim 7, characterized in that: The inner diameter of the quartz glass tube is 1-2cm, and the wall thickness is 2-3mm; the length of a single quartz glass tube is 50-100cm; the length of the ultraviolet lamp is consistent with that of a single quartz tube; the length of the ultraviolet lamp is 50-100cm; the arrangement combination of the ultraviolet lamps is 2 at an angle of 180°, 3 at an angle of 120°, or 4 at an angle of 90°.

9. The method for preparing PGMA porous microspheres by light initiation according to claim 1, characterized in that: The continuous loading described in S6 requires that the material be irradiated under the two sets of ultraviolet lamps for the same length of time, with a total irradiation time of 30-60 minutes.

10. PGMA porous microspheres prepared by the preparation method according to any one of claims 1 to 9.

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