CN112646067B - Method for synthesizing monodisperse polymer microspheres in pure water medium - Google Patents
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- 239000004005 microsphere Substances 0.000 title claims abstract description 71
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- 239000000839 emulsion Substances 0.000 claims description 4
- -1 alkali metal salt Chemical class 0.000 claims description 3
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- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
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- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
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- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 claims description 2
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- 238000001878 scanning electron micrograph Methods 0.000 description 12
- 239000008367 deionised water Substances 0.000 description 9
- 229910021641 deionized water Inorganic materials 0.000 description 9
- 238000012674 dispersion polymerization Methods 0.000 description 9
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 6
- 239000001632 sodium acetate Substances 0.000 description 6
- 235000017281 sodium acetate Nutrition 0.000 description 6
- RIWRBSMFKVOJMN-UHFFFAOYSA-N 2-methyl-1-phenylpropan-2-ol Chemical compound CC(C)(O)CC1=CC=CC=C1 RIWRBSMFKVOJMN-UHFFFAOYSA-N 0.000 description 5
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- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 238000006116 polymerization reaction Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
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- 230000009286 beneficial effect Effects 0.000 description 2
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- 238000005516 engineering process Methods 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 230000036632 reaction speed Effects 0.000 description 2
- 238000010557 suspension polymerization reaction Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- XMLYCEVDHLAQEL-UHFFFAOYSA-N 2-hydroxy-2-methyl-1-phenylpropan-1-one Chemical compound CC(C)(O)C(=O)C1=CC=CC=C1 XMLYCEVDHLAQEL-UHFFFAOYSA-N 0.000 description 1
- 239000012957 2-hydroxy-2-methyl-1-phenylpropanone Substances 0.000 description 1
- QZPSOSOOLFHYRR-UHFFFAOYSA-N 3-hydroxypropyl prop-2-enoate Chemical compound OCCCOC(=O)C=C QZPSOSOOLFHYRR-UHFFFAOYSA-N 0.000 description 1
- OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 1
- WIYVVIUBKNTNKG-UHFFFAOYSA-N 6,7-dimethoxy-3,4-dihydronaphthalene-2-carboxylic acid Chemical compound C1CC(C(O)=O)=CC2=C1C=C(OC)C(OC)=C2 WIYVVIUBKNTNKG-UHFFFAOYSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- CNCOEDDPFOAUMB-UHFFFAOYSA-N N-Methylolacrylamide Chemical compound OCNC(=O)C=C CNCOEDDPFOAUMB-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- FQPSGWSUVKBHSU-UHFFFAOYSA-N methacrylamide Chemical compound CC(=C)C(N)=O FQPSGWSUVKBHSU-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- QNILTEGFHQSKFF-UHFFFAOYSA-N n-propan-2-ylprop-2-enamide Chemical compound CC(C)NC(=O)C=C QNILTEGFHQSKFF-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- BWILYWWHXDGKQA-UHFFFAOYSA-M potassium propanoate Chemical compound [K+].CCC([O-])=O BWILYWWHXDGKQA-UHFFFAOYSA-M 0.000 description 1
- 239000004331 potassium propionate Substances 0.000 description 1
- 235000010332 potassium propionate Nutrition 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- JXKPEJDQGNYQSM-UHFFFAOYSA-M sodium propionate Chemical compound [Na+].CCC([O-])=O JXKPEJDQGNYQSM-UHFFFAOYSA-M 0.000 description 1
- 239000004324 sodium propionate Substances 0.000 description 1
- 235000010334 sodium propionate Nutrition 0.000 description 1
- 229960003212 sodium propionate Drugs 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000013269 sustained drug release Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229920003176 water-insoluble polymer Polymers 0.000 description 1
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- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F120/00—Homopolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride, ester, amide, imide or nitrile thereof
- C08F120/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F120/10—Esters
- C08F120/20—Esters of polyhydric alcohols or polyhydric phenols, e.g. 2-hydroxyethyl (meth)acrylate or glycerol mono-(meth)acrylate
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
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- C08F2/00—Processes of polymerisation
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- C08F2/00—Processes of polymerisation
- C08F2/46—Polymerisation initiated by wave energy or particle radiation
- C08F2/48—Polymerisation initiated by wave energy or particle radiation by ultraviolet or visible light
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Abstract
The invention belongs to the technical field of polymer microsphere preparation, and particularly relates to a method for synthesizing monodisperse polymer microspheres in a pure water medium. On one hand, the problem that the microspheres cannot be formed due to the fact that the dissolution characteristics of the monomers and the obtained polymers in water are influenced by temperature factors can be avoided, and on the other hand, the problem that the monodisperse microspheres are difficult to form due to too fast nucleation and growth is solved. At the same time. Because the invention uses water to replace organic solvent as dispersion medium, the influence of organic solvent on biological medicine can be avoided, and the invention has no pollution to environment. In addition, the invention is favorable for the synthesis of the microspheres with the biomedical load because the invention does not need heating.
Description
Technical Field
The invention belongs to the technical field of polymer microsphere preparation, and particularly relates to a method for synthesizing monodisperse polymer microspheres in a pure water medium.
Background
Biological and medical techniques often require the use of polymeric microspheres as carriers, such as biomolecule recognition, targeted drug delivery, sustained drug release, and the like. In these applications, the preparation of microspheres is often carried out in a non-organic solvent medium, and the synthesis process is also carried out at an excessive temperature so as not to denature the biomedical components under the influence of organic solvents. The existing polymer microsphere synthesis system mainly comprises emulsion polymerization, suspension polymerization and dispersion polymerization, wherein the emulsion polymerization can adopt pure water as a medium, but the emulsion polymerization needs an emulsifier, and the particle size control of microspheres is inflexible; suspension polymerization can also be carried out using pure water as the medium, but the resulting microspheres have poor particle size uniformity. Dispersion polymerization is used as a mature polymer microsphere synthesis system, monodisperse microspheres with the particle size of 0.1-15mm can be synthesized, and the preparation of microspheres by dispersion polymerization in an aqueous medium is also reported, but because the polymerization reaction needs to be carried out under a heating condition, the reaction time is as long as 24 hours, and the conditions are limited in some biological applications. Moreover, since dispersion polymerization has special requirements on the solubility of monomers and polymers (monomers need to be dissolved in a dispersion medium, and polymers must be precipitated when reaching a certain chain length), when an aqueous medium is used, the influence of temperature on the solubility of monomers and polymers is particularly obvious, so that microspheres are not uniform, and even cannot be obtained. The light initiation system can be adopted to rapidly carry out dispersion polymerization at normal temperature, but because the reaction speed is too high, nucleation is easy to interfere, and growing microspheres cannot be stabilized in time, so that monodisperse microspheres are difficult to obtain. Therefore, there is a need to develop a method for preparing polymer microspheres with uniform particle size distribution in pure water and at low temperature.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention provides a method for synthesizing monodisperse polymer microspheres in a pure water medium, the method can prepare the polymer microspheres with uniform particle size distribution in pure water and at low temperature, and the method is environment-friendly and pollution-free and is beneficial to the synthesis of microspheres with biomedical loads.
In order to achieve the purpose, the invention adopts the technical scheme that:
the invention provides a method for synthesizing monodisperse polymer microspheres in a pure water medium, which comprises the steps of dissolving a polymer monomer, a stabilizer, a water-soluble salt, a water-soluble reversible chain transfer agent and a photoinitiator in pure water, then carrying out ultraviolet illumination at normal temperature in an inert gas atmosphere, obtaining a stable white emulsion after illumination for a period of time, and separating and washing the white emulsion to obtain the monodisperse polymer microspheres.
The method aims to solve the problems that the temperature of a polymer microsphere dispersion polymerization method during water dispersion high-temperature polymerization can cause the non-uniformity of microspheres, even microspheres can not be obtained, or nucleation is easy to interfere and monodisperse microspheres are difficult to obtain due to too high reaction speed during water dispersion normal-temperature polymerization. The invention provides an improved polymer microsphere dispersion polymerization method, which introduces a photoinitiation technology when pure water is used for replacing an organic solvent as a dispersion medium, so that the reaction process does not need to be heated, the hydrophilicity and hydrophobicity of monomers and polymers cannot be influenced due to heating, and a water-soluble reversible chain transfer reagent is introduced to regulate and control the nucleation speed, so that the problem of uneven particle size distribution of microspheres is solved, and the yield is greatly improved while monodisperse microspheres are obtained. In addition, a small amount of water-soluble salt is added into the system, and the competition of cations between the chain transfer agent and acid radicals is utilized to balance the affinity of the chain transfer agent in water and the polymeric microspheres, so that the regulation and control effects of the chain transfer agent on the nucleation and microsphere growth processes are fully exerted. Finally, the invention can prepare the polymer microspheres with uniform particle size distribution in pure water and at low temperature. Because water is used to replace organic solvent as dispersion medium, the invention can avoid the influence of organic solvent on biological medicine, and has no pollution to environment.
Preferably, the amount of the polymer monomer is 5-20 wt% of the reaction system, the amount of the photoinitiator is 0.5-5 wt% of the polymer monomer, the amount of the stabilizer is 5-25 wt% of the polymer monomer, the amount of the water-soluble salt is 0.1-2 wt% of the reaction system, and the amount of the water-soluble reversible chain transfer agent is 0.25-0.75 wt% of the polymer monomer. Further, the amount of the polymer monomer is 5-10 wt% of the reaction system, the amount of the photoinitiator is 2-3 wt% of the polymer monomer, the amount of the stabilizer is 10-15 wt% of the polymer monomer, the amount of the water-soluble salt is 0.5-1 wt% of the reaction system, and the amount of the water-soluble reversible chain transfer agent is 0.25-0.5 wt% of the polymer monomer.
Preferably, the time of ultraviolet illumination is 1-6 h. Further, the time of ultraviolet irradiation is 4 hours.
Preferably, the polymer monomer is at least one of hydroxypropyl acrylate (HPMA), 2- (dimethylamino) ethyl methacrylate, N-methylolacrylamide, N-dimethylacrylamide, N-isopropylacrylamide, acrylamide, and methacrylamide. In principle, other water-soluble monomers which can be polymerized to give water-insoluble polymers are suitable for the present invention.
Preferably, the water-soluble reversible chain transfer agent includes, but is not limited to, S' -bis (2-methyl-2-propanoic acid) trithiocarbonate (BDMAT). In principle, other water-soluble reversible chain transfer agents that achieve the same or similar effect are suitable for use in the present invention.
Preferably, the stabilizer includes, but is not limited to, polyvinylpyrrolidone (PVP). In principle, hydrophilic stabilizers used in general dispersion polymerization can be used as the stabilizer in the present invention, and there is no particular limitation in the present technology.
Preferably, the photoinitiator is a hydrophilic free radical photoinitiator. Further, the photoinitiator is selected from at least one of 2-hydroxy-2-methyl-1-phenylpropanone (Darocur 1173), 2-hydroxy-1- (4- (2-hydroxy-2-methylpropanoylphenyl) -2-methyl-1-propanone) and 1-hydroxy-cyclohexyl-phenone. In principle, other hydrophilic radical photoinitiators which achieve the same or similar effect are suitable for use in the present invention.
Preferably, the water-soluble salt is an organic acid alkali metal salt. Further, the water-soluble salt is selected from at least one of sodium acetate, potassium acetate, sodium propionate and potassium propionate. Specifically, the water-soluble salt is sodium acetate.
Preferably, the ultraviolet light irradiation adopts any one of a medium-pressure mercury lamp, an ultraviolet electrodeless lamp, a metal halogen lamp or a UV-LED light source, the radiation wavelength is 365nm, and the light intensity is 0.5-100 mW/cm2。
Preferably, the pure water is deionized water.
The invention also provides the monodisperse polymer microsphere prepared by the method.
Compared with the prior art, the invention has the beneficial effects that:
the invention provides a method for synthesizing monodisperse polymer microspheres in a pure water medium, which is characterized in that water-soluble salt, a water-soluble reversible chain transfer agent and a photoinitiator are added in the dispersion polymerization process of the polymer microspheres, so that the polymer microspheres with uniform particle size distribution can be prepared in pure water and under the low-temperature condition. On one hand, the problem that the microspheres cannot be formed due to the fact that the dissolution characteristics of the monomers and the obtained polymers in water are influenced by temperature factors can be avoided, and on the other hand, the problem that the monodisperse microspheres are difficult to form due to too fast nucleation and growth is solved. At the same time. Because the invention uses water to replace organic solvent as dispersion medium, the influence of organic solvent on biological medicine can be avoided, and the invention has no pollution to environment. In addition, the invention is favorable for the synthesis of the microspheres with the biomedical load because the invention does not need heating.
Drawings
FIG. 1 is a Scanning Electron Micrograph (SEM) of polymeric microspheres prepared in example 1;
FIG. 2 is a Scanning Electron Micrograph (SEM) of the polymeric microspheres prepared in example 2;
FIG. 3 is a Scanning Electron Micrograph (SEM) of polymeric microspheres prepared in example 3;
FIG. 4 is a Scanning Electron Micrograph (SEM) of polymeric microspheres prepared in example 4;
FIG. 5 is a Scanning Electron Micrograph (SEM) of polymeric microspheres prepared according to comparative example 5;
fig. 6 is a Scanning Electron Micrograph (SEM) of the polymeric microspheres prepared in comparative example 6.
Detailed Description
The following further describes the embodiments of the present invention. It should be noted that the description of the embodiments is provided to help understanding of the present invention, but the present invention is not limited thereto. In addition, the technical features involved in the embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
The experimental procedures in the following examples were carried out by conventional methods unless otherwise specified, and the test materials used in the following examples were commercially available by conventional methods unless otherwise specified.
Example 1A method for synthesizing monodisperse Polymer microspheres in a pure Water Medium
Under a normal-temperature nitrogen atmosphere, 18g of deionized water, 2.0g of HPMA monomer (10 wt% relative to the reaction system), 0.30g of PVP (15 wt% relative to the monomer), 0.005g of BDMAT (0.25 wt% relative to the monomer), 0.040g of Darocur1173 photoinitiator (2 wt% relative to the monomer) and 0.10g of sodium acetate (0.5 wt% relative to the reaction system) were added into a 50mL single-neck flask, stirred uniformly by magnetic force, and then irradiated by an ultraviolet lamp (ultraviolet electrodeless lamp, the radiation wavelength was 365nm, and the light intensity was 50mW/cm2) Irradiation was carried out for 4h from above the reactor. After centrifugal separation, the reaction product is washed by deionized water, the washing is repeated for 2-3 times, then the white powder (namely the polymer microsphere) is obtained by drying in a vacuum oven, the conversion rate is calculated by a gravimetric method, the yield is more than 90%, a scanning electron microscope is shown in figure 1, and the polymer microsphere with uniform particle size is obtained by the synthesis in the embodiment.
Example 2A method for synthesizing monodisperse Polymer microspheres in a pure Water Medium
Under a normal-temperature nitrogen atmosphere, 18g of deionized water, 1.0g of HPMA monomer (5 wt% relative to the reaction system), 0.20g of PVP (10 wt% relative to the monomer), 0.005g of BDMAT (0.25 wt% relative to the monomer), 0.040g of Darocur1173 photoinitiator (2 wt% relative to the monomer) and 0.10g of sodium acetate (0.5 wt% relative to the reaction system) were added into a 50mL single-neck flask, stirred uniformly by magnetic force, and then irradiated by an ultraviolet lamp (ultraviolet electrodeless lamp, the radiation wavelength was 365nm, and the light intensity was 30mW/cm2) Irradiation was carried out for 4h from above the reactor. After centrifugal separation, the reaction product is washed by deionized water, the washing is repeated for 2-3 times, then the white powder (namely the polymer microsphere) is obtained by drying in a vacuum oven, the conversion rate is calculated by a gravimetric method, the yield is more than 90%, a scanning electron microscope is shown in figure 2, and the polymer microsphere with uniform particle size is obtained by the synthesis in the embodiment.
Example 3A method for synthesizing monodisperse Polymer microspheres in a pure Water Medium
18g of deionized water, 2.0g of an HPMA monomer (10% by weight relative to the reaction system), 0.30g of PVP (15% by weight relative to the monomer), 0.005g of BDMAT (0.25% by weight relative to the monomer), 0.060g of Darocur1173 photoinitiator (3% by weight relative to the monomer) and 0.20g of sodium acetate (1% by weight relative to the reaction system) were placed in a 50mL single-necked flask under a normal-temperature nitrogen atmosphere, stirred uniformly by magnetic force, and then irradiated with an ultraviolet lamp (ultraviolet electrodeless lamp, with a radiation wavelength of 365nm and a light intensity of 0.5mW/cm2) Irradiation was carried out for 4h from above the reactor. After centrifugal separation, the reaction product is washed by deionized water, the washing is repeated for 2-3 times, then the white powder (namely the polymer microsphere) is obtained by drying in a vacuum oven, the conversion rate is calculated by a gravimetric method, the yield is more than 90%, a scanning electron microscope is shown in figure 3, and the polymer microsphere with uniform particle size is obtained by the synthesis in the embodiment.
Example 4A method for synthesizing monodisperse Polymer microspheres in a pure Water Medium
Under the atmosphere of normal temperature nitrogen, 18g of deionized water, 2.0g of HPMA monomer (10 wt% relative to the reaction system), 0.30g of PVP (15 wt% relative to the monomer), 0.010g of BDMAT (0.5 wt% relative to the monomer), 0.040g of Darocur1173 photoinitiator (2 wt% relative to the monomer) and 0.10g of sodium acetate (0.5 wt% relative to the reaction system) were added into a 50mL single-neck flask, stirred uniformly by magnetic force, and then irradiated by ultraviolet light (ultraviolet electrodeless lamp, the radiation wavelength was 365nm, and the light intensity was 100mW/cm2) Irradiation was carried out for 4h from above the reactor. After centrifugal separation, the reaction product is washed by deionized water, the washing is repeated for 2-3 times, then the white powder (namely the polymer microsphere) is obtained by drying in a vacuum oven, the conversion rate is calculated by a gravimetric method, the yield is more than 90%, a scanning electron microscope is shown in figure 4, and the polymer microsphere with uniform particle size is obtained by the synthesis in the embodiment.
Comparative example 1 method for synthesizing monodisperse Polymer microspheres in pure Water Medium
In this example, a water-soluble chain transfer agent and a water-soluble salt were not added as compared with example 1, and other conditions and operation methods were the same as those of example 1. As can be seen from the scanning electron microscope of fig. 5, the uniformity of the obtained microspheres was poor due to the absence of the water-soluble reversible chain transfer agent and the water-soluble salt.
Comparative example 2 method for synthesizing monodisperse Polymer microspheres in pure Water Medium
In comparison with example 1, this example was conducted under the same conditions and in the same manner as example 1 except that no water-soluble salt was added. As can be seen from the scanning electron microscope in fig. 6, after the water-soluble reversible chain transfer agent is used, the polymeric microspheres can be obtained, but since a proper amount of water-soluble salt is not added in the present embodiment, the uniformity of the obtained microspheres is poor.
The embodiments of the present invention have been described in detail, but the present invention is not limited to the described embodiments. It will be apparent to those skilled in the art that various changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, and the scope of protection is still within the scope of the invention.
Claims (9)
1. A method for synthesizing monodisperse polymer microspheres in a pure water medium is characterized in that HPMA monomers, a stabilizer, water-soluble salt, a water-soluble reversible chain transfer agent and a photoinitiator are dissolved in pure water, then ultraviolet illumination is carried out at normal temperature under the atmosphere of inert gas, stable white emulsion is obtained after illumination is carried out for a period of time, and the preparation is carried out after the white emulsion is separated and washed.
2. The method for synthesizing monodisperse polymer microspheres in pure water medium according to claim 1, wherein the amount of the HPMA monomer is 5-20 wt% of the reaction system, the amount of the photoinitiator is 0.5-5 wt% of the polymer monomer, the amount of the stabilizer is 5-25 wt% of the polymer monomer, the amount of the water-soluble salt is 0.1-2 wt% of the reaction system, and the amount of the water-soluble reversible chain transfer agent is 0.25-0.75 wt% of the polymer monomer.
3. The method for synthesizing monodisperse polymer microspheres according to claim 1, wherein the time of ultraviolet irradiation is 1-6 hours.
4. The method of claim 1, wherein the water soluble reversible chain transfer agent includes, but is not limited to, S' -bis (2-methyl-2-propanoic acid) trithiocarbonate.
5. The method of claim 1, wherein the stabilizing agent includes but is not limited to polyvinylpyrrolidone.
6. The method of claim 1, wherein the photoinitiator is a hydrophilic free radical photoinitiator.
7. The method of claim 1, wherein the water soluble salt is an alkali metal salt of an organic acid.
8. The method for synthesizing monodisperse polymer microspheres in pure water medium according to claim 1, wherein any one of a medium-pressure mercury lamp, an ultraviolet electrodeless lamp, a metal halogen lamp or a UV-LED light source is adopted for ultraviolet illumination, the radiation wavelength is 365nm, and the light intensity is 0.5-100 mW/cm2。
9. Monodisperse polymeric microspheres obtainable by a process according to any one of claims 1-8.
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