CN114213581A - Preparation method of hydrophilic polyacrylate crosslinked microspheres - Google Patents
Preparation method of hydrophilic polyacrylate crosslinked microspheres Download PDFInfo
- Publication number
- CN114213581A CN114213581A CN202111566182.5A CN202111566182A CN114213581A CN 114213581 A CN114213581 A CN 114213581A CN 202111566182 A CN202111566182 A CN 202111566182A CN 114213581 A CN114213581 A CN 114213581A
- Authority
- CN
- China
- Prior art keywords
- reaction
- monomer
- hydrophilic
- transferring
- mixture
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers 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
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/10—Esters
- C08F220/34—Esters containing nitrogen, e.g. N,N-dimethylaminoethyl (meth)acrylate
- C08F220/36—Esters containing nitrogen, e.g. N,N-dimethylaminoethyl (meth)acrylate containing oxygen in addition to the carboxy oxygen, e.g. 2-N-morpholinoethyl (meth)acrylate or 2-isocyanatoethyl (meth)acrylate
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
Abstract
The invention relates to the technical field of high polymer materials, and provides a preparation method of hydrophilic polyacrylate crosslinked microspheres, which comprises the following steps: (1) amination of the comonomer; (2) preparation of hydrophilic comonomer: (3) preparing a stable phase; (4) polymerization and the like. The method connects the hydrophilic substance to the comonomer in a chemical bonding mode, and then performs copolymerization reaction with the crosslinking agent to form the polymer microsphere.
Description
Technical Field
The invention relates to the technical field of high polymer materials, in particular to a preparation method of hydrophilic polyacrylate crosslinked microspheres.
Background
Polysaccharides such as cellulose, agarose and cross-linked dextran were the earliest chromatographic media used for protein separation and are the most commonly used separation media. The separation medium is typical hydrophilic resin, has good compatibility with water-soluble biological macromolecules, and can be directly applied to biological separation. However, polysaccharide resins have natural disadvantages, such as insufficient mechanical strength, and when the flow rate is increased, the medium is squeezed, and the column pressure is increased, and if the flow rate exceeds the critical flow rate, the polysaccharide medium may be deformed, and the separation performance of the polysaccharide medium is affected; in addition, polysaccharide separation media are increasingly limited in the field of monoclonal antibody drug and protein separation because of the difficulty in rapid separation of biological macromolecules due to the narrow pore channel.
Polymer separation media such as polyacrylates and polystyrene-divinylbenzene polymer microspheres have excellent mechanical properties and stable chemical properties, and the advantages of large and adjustable pore size gradually attract the attention of researchers in the field of biological separation, but the self framework of the polymer separation media has longer C-C bonds and contains ester bonds or benzene rings, so that the polymer separation media have specific adsorption to biological substances and even cause the denaturation of biological macromolecules, and therefore, the polymer separation media cannot be directly applied to the separation of the biological macromolecules. However, if a polyhydroxy compound is bonded on the surface of polystyrene microspheres, the specific adsorption of the polystyrene microspheres to biological macromolecules can be eliminated, and the method can be applied to the field of biological macromolecule separation, for example, in Chinese patent (ZL201510671362.8), PVA is bonded on the surface of the polystyrene microspheres through chloromethylation on the surface of the polystyrene microspheres, so that the specific adsorption of PVA to biological macromolecules can be reduced or reduced, and the PVA contains a large number of hydroxyl groups, so that the specific ligands can be conveniently coupled to meet the requirements of different separation modes. But the process is complex, the steps are complicated and difficult to control. The polyacrylate microspheres have certain hydrophobicity, so that the polyacrylate microspheres cannot be directly applied to the field of separation of biomacromolecules.
Disclosure of Invention
Therefore, aiming at the defects of the prior art, the invention aims to provide a preparation method of hydrophilic polyacrylate crosslinked microspheres, which comprises the steps of firstly modifying an acrylate polymerizable monomer through polyhydroxy hydrophilization, then copolymerizing the acrylate polymerizable monomer with a crosslinking agent in a water phase containing a stabilizing agent, retaining polyhydroxy groups on the surfaces of the crosslinked microspheres, reducing the hydrophobicity of the surfaces of the polyacrylate microspheres and improving the biocompatibility of the polyacrylate microspheres; the original structure of the polyacrylate microsphere can be maintained, higher flow rate can be borne, meanwhile, the polyhydroxy structure on the surface of the microsphere is convenient for further derivatization, and can be coupled with specific ligands, so that the field of separation and purification of biomacromolecules is expanded.
The invention provides a preparation method of hydrophilic polyacrylate crosslinked microspheres.
In order to achieve the purpose, the invention is realized by the following technical scheme:
a preparation method of hydrophilic polyacrylate crosslinked microspheres comprises the following steps:
(1) amination of the comonomer: weighing a proper amount of monomer M1 into a round bottom reaction bottle, adding a proper amount of solvents S1 and A1, uniformly stirring, heating to 40-100 ℃, and reacting for 0.5-8 h; after the reaction is finished, obtaining an amination monomer for later use;
(2) preparation of hydrophilic comonomer: transferring the aminated monomer in the step (1) into a reaction bottle, adding a solvent S2, uniformly stirring, adding a proper amount of glucolactone, heating to 40-100 ℃, and reacting for 0.5-8 h; after the reaction is finished, obtaining a hydrophilic comonomer M2;
(3) preparation of the stable phase: adding a proper amount of stabilizer P1 into deionized water, heating to 50-80 ℃, and obtaining an aqueous phase solution containing stabilizer P1 after the stabilizer is completely dissolved;
(4) polymerization: weighing a proper amount of polymerizable monomers M2, M3, a pore-forming agent P2 and an initiator I1 in a beaker, and uniformly mixing for later use; weighing a proper amount of S3 and a proper amount of polymerization inhibitor Z1 in a beaker, adding deionized water, and completely dissolving; adding an emulsifier S4, uniformly dispersing, and transferring to a reaction bottle; transferring the stable phase obtained in (3) to a reaction flask; stirring uniformly; transferring oily solution containing M2, M3, P3 and I1 into a reaction bottle, heating to 65-90 ℃ at the stirring speed of 50-1000rpm, and carrying out heat preservation reaction for 8-18 h; after the reaction is finished, cooling to room temperature, filtering reaction liquid, and sequentially cleaning with methanol or ethanol or acetone and deionized water to obtain the hydrophilic polyacrylate crosslinked microspheres with a large number of hydroxyl groups on the surfaces.
The further improvement is that: the mass ratio of the monomer A1 to the monomer M1 to the monomer S1 is (0.5-5) to 10 to (2-10).
The further improvement is that: the mass ratio of the aminated monomer to the gluconolactone to the solvent S2 is 1: 0.5-30: 2-80.
The further improvement is that: the mass ratio of the stabilizer P1 to water is 0.5-5: 100. The mass ratio of I1 to M2 to M3 to P2 is (0.5-2) to (2-80) to (100) to (2-200). The mass ratio of the S3 to the water is 5-20: 100. The mass ratio of the oil phase to the water in the step (4) is 5-30: 100.
The further improvement is that: the polymerizable monomer M1 is any one or a mixture of glycidyl methacrylate and glycidyl acrylate.
The further improvement is that: the A1 is one or two of ethylenediamine, propylenediamine, butylenediamine, pentylenediamine, hexylenediamine, octylenediamine, diethylenetriamine, triethylenetetramine and tetraethylenepentamine.
The further improvement is that: the solvent S1 is any one or two mixtures of methanol, ethanol, dioxane and dimethyl sulfoxide.
The further improvement is that: the solvent S2 is any one or two mixtures of dioxane and dimethyl sulfoxide.
The further improvement is that: the stabilizer P1 is one or more of polyvinyl alcohol, polyethylene glycol, polyvinylpyrrolidone, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, beta-cyclodextrin, beta-methyl cyclodextrin and hydroxyapatite.
The further improvement is that: the crosslinking agent M3 is any one or a mixture of more than two of divinylbenzene, dipropylene benzene, ethylene glycol dimethacrylate, triethylene glycol, trimethylolpropane trimethacrylate, pentaerythritol triacrylate, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, 1, 3-butanediol dimethacrylate, 1, 4-butanediol dimethacrylate hexamethylene dimethacrylate, divinylphenyl methane, glyceryl trimethacrylate and methylene acrylamide.
The further improvement is that: the pore-foaming agent P2 is any one or a mixture of more than two of toluene, isobutanol, cyclohexanol, n-hexane, n-heptane, dodecanol, dimethyl phthalate and dibutyl phthalate.
The further improvement is that: the salt S3 is one or more of sodium chloride, sodium sulfate, sodium nitrate, sodium phosphate, sodium hydrogen phosphate and sodium dihydrogen phosphate.
The further improvement is that: the polymerization inhibitor Z1 is any one or a mixture of more than two of sodium nitrite, hydroquinone and sodium p-nitrophenolate.
The further improvement is that: the emulsifier S4 is one or a mixture of ionic emulsifier and non-ionic emulsifier in any ratio. The ionic emulsifier is alkylbenzene sulfonate, alkyl succinate sulfonate or alkyl diphenyl ether sulfonate. The non-ionic emulsifier is alkylphenol polyoxyethylene, benzyl phenol polyoxyethylene, phenethyl phenol polyoxyethylene, fatty alcohol polyoxyethylene or fatty amine polyoxyethylene.
The further improvement is that: the initiator I1 is any one or a mixture of more than two of benzoyl peroxide, azobisisobutyronitrile, dimethyl azobisisobutyrate and azobisisobutylamidine.
The invention has the characteristics that:
by adopting the technical scheme, the invention has the beneficial effects that:
the invention prepares a hydrophilic polyacrylate crosslinked microsphere, firstly, a polymerizable monomer is aminated, then, gluconolactone is bonded, polyhydroxy is introduced into a polymerizable acrylate compound, and then, the polyhydroxy and a crosslinking agent are copolymerized into a spherical shape in a water phase containing a stabilizing agent. The polymerizable monomer has a definite structure, the hydroxyl-containing part has stronger hydrophilicity and is repelled with an oily cross-linking agent, and after copolymerization with the cross-linking agent, the hydrophilic polyhydroxy end is extruded to the surface of the microsphere, so that the polyhydroxy and hydrophilic polyacrylate cross-linked microsphere can be obtained. The method also has the following advantages: the synthesis method has the advantages of simplicity, definite structure, easy control, convenience for scale-up production and the like, and has potential application value in biomacromolecule and in vitro diagnosis.
Detailed Description
The following detailed description will be provided for the embodiments of the present invention with reference to specific embodiments, so that how to apply the technical means to solve the technical problems and achieve the technical effects can be fully understood and implemented.
Unless otherwise indicated, the techniques employed in the examples are conventional and well known to those skilled in the art, and the reagents and products employed are also commercially available. The source, trade name and if necessary the constituents of the reagents used are indicated at the first appearance.
Example one
A preparation method of hydrophilic polyacrylate crosslinked microspheres comprises the following steps:
(1) amination of the comonomer:
weighing 10g of monomer glycidyl methacrylate in a round bottom reaction bottle, adding 5g of methanol and 2g of ethylenediamine, uniformly stirring, heating to 50 ℃, and reacting for 8 hours; after the reaction is finished, obtaining an amination monomer for later use;
(2) preparation of hydrophilic comonomer:
transferring the aminated monomer in the step (1) to a reaction bottle, adding a solvent dimethyl sulfoxide, uniformly stirring, adding 5g of gluconolactone, heating to 40 ℃, and reacting for 10 hours; after the reaction is finished, hydrophilic comonomer is obtained;
(3) preparation of the stable phase:
weighing 20g of deionized water in a reaction bottle, continuously adding 1g of polyvinyl alcohol, heating to 80 ℃, and stirring until the polyvinyl alcohol is completely dissolved for later use.
(4) Polymerisation
Transferring the hydrophilic comonomer obtained in the step (2) into a beaker, weighing 10g of divinylbenzene, 20g of toluene and 0.5g of azobisisobutyronitrile into the beaker, and stirring until the azobisisobutyronitrile is completely dissolved; weighing 4g of sodium chloride and 0.05g of sodium nitrite in a beaker, adding 200g of deionized water, adding 0.4g of SDS, stirring until the sodium chloride is completely dissolved, and transferring the mixture into a reaction bottle; transferring the stable phase into a reaction flask; stirring uniformly; continuously transferring the oily monomer into a reaction bottle, heating the system to 80 ℃ under the condition of stirring at 220rpm, and carrying out heat preservation reaction for 8 hours; after the reaction is finished, cooling to room temperature, filtering by using filter cloth, and respectively washing by using 10 times of ethanol and deionized water to obtain the hydrophilic polyacrylate crosslinked microspheres with the average particle size of 40.3 mu m.
Example two
A preparation method of hydrophilic polyacrylate crosslinked microspheres comprises the following steps:
(1) amination of the comonomer:
weighing 10g of monomer glycidyl methacrylate in a round bottom reaction bottle, adding 5g of dioxane and 2g of hexamethylenediamine, uniformly stirring, heating to 60 ℃, and reacting for 4 hours; after the reaction is finished, obtaining an amination monomer for later use;
(2) preparation of hydrophilic comonomer:
transferring the aminated monomer in the step (1) into a reaction bottle, adding a solvent dimethyl sulfoxide, uniformly stirring, adding 6.1g of glucolactone, heating to 50 ℃, and reacting for 6 hours; after the reaction is finished, hydrophilic comonomer is obtained;
(3) preparation of the stable phase:
weighing 25g of deionized water in a reaction bottle, continuously adding 1.5g of polyvinylpyrrolidone, heating to 80 ℃, and stirring until the polyvinylpyrrolidone is completely dissolved for later use.
(4) Polymerisation
Transferring the hydrophilic comonomer obtained in the step (2) into a beaker, weighing 10g of ethylene glycol dimethacrylate, 20g of cyclohexanol and 0.1g of benzoyl peroxide into the beaker, and stirring until the benzoyl peroxide is completely dissolved; weighing 2g of sodium sulfate and 0.04g of sodium p-phenylenediphenolate in a beaker, adding 200g of deionized water, adding 0.4g of SDBS, stirring until the sodium sulfate is completely dissolved, and transferring the mixture into a reaction bottle; transferring the stable phase into a reaction flask; stirring uniformly; continuously transferring the oily monomer into a reaction bottle, heating the system to 75 ℃ under stirring at 180rpm, and carrying out heat preservation reaction for 14 hours; after the reaction is finished, cooling to room temperature, filtering by using filter cloth, and respectively washing by using 10 times of ethanol and deionized water to obtain the hydrophilic polyacrylate crosslinked microspheres with the average particle size of 54.1 mu m.
EXAMPLE III
A preparation method of hydrophilic polyacrylate crosslinked microspheres comprises the following steps:
(1) amination of the comonomer:
weighing 10g of monomer glycidyl acrylate in a round bottom reaction bottle, adding 5g of dimethyl sulfoxide and 3g of butanediamine, uniformly stirring, heating to 60 ℃, and reacting for 7 hours; after the reaction is finished, obtaining an amination monomer for later use;
(2) preparation of hydrophilic comonomer:
transferring the aminated monomer in the step (1) into a reaction bottle, adding a solvent dimethyl sulfoxide, uniformly stirring, adding 4.1g of gluconolactone, heating to 50 ℃, and reacting for 6 hours; after the reaction is finished, hydrophilic comonomer is obtained;
(3) preparation of the stable phase:
weighing 25g of deionized water into a reaction bottle, continuously adding 1.5g of beta-cyclodextrin, heating to 80 ℃, and stirring until the beta-cyclodextrin is completely dissolved for later use.
(4) Polymerisation
Transferring the hydrophilic comonomer obtained in the step (2) into a beaker, weighing 4g of 1, 3-butanediol dimethacrylate, 7.21g of dodecanol and 0.1g of azobisisobutyronitrile into the beaker, and stirring until the azobisisobutyronitrile is completely dissolved; weighing 0.7g of sodium chloride and 0.03g of sodium nitrite in a beaker, adding 200g of deionized water, adding 0.4g of triton X-104, stirring until the sodium chloride is completely dissolved, and transferring the mixture into a reaction bottle; transferring the stable phase into a reaction flask; stirring uniformly; continuously transferring the oily monomer into a reaction bottle, heating the system to 65 ℃ under stirring at 180rpm, and carrying out heat preservation reaction for 18 hours; after the reaction is finished, cooling to room temperature, filtering by using filter cloth, and respectively washing by using 10 times of ethanol and deionized water to obtain the hydrophilic polyacrylate crosslinked microspheres with the average particle size of 28.7 mu m.
Example four
A preparation method of hydrophilic polyacrylate crosslinked microspheres comprises the following steps:
(1) amination of the comonomer:
weighing 10g of monomer glycidyl methacrylate in a round bottom reaction bottle, adding 2g of ethanol and 3g of ethylenediamine, uniformly stirring, heating to 50 ℃, and reacting for 8 hours; after the reaction is finished, obtaining an amination monomer for later use;
(2) preparation of hydrophilic comonomer:
transferring the aminated monomer in the step (1) into a reaction bottle, adding a solvent dimethyl sulfoxide, uniformly stirring, adding 4.4g of gluconolactone, heating to 50 ℃, and reacting for 6 hours; after the reaction is finished, hydrophilic comonomer is obtained;
(3) preparation of the stable phase:
weighing 25g of deionized water into a reaction bottle, continuously adding 1.5g of polyvinyl alcohol, heating to 80 ℃, and stirring until the polyvinyl alcohol is completely dissolved for later use.
(4) Polymerisation
Transferring the hydrophilic comonomer obtained in the step (2) into a beaker, weighing 4.8g of diethylene glycol dimethacrylate, 14.8g of o-xylylene dibutyl ester and 0.08g of azodiisobutyl amidine into the beaker, and stirring until the azodiisobutyl amidine is completely dissolved; weighing 1.07g of sodium chloride and 0.34g of sodium dihydrogen phosphate into a beaker and 0.06g of sodium p-nitrophenolate, adding 200g of deionized water, adding 0.4g of SDS, stirring until the sodium chloride and the sodium dihydrogen phosphate are completely dissolved, and transferring into a reaction bottle; transferring the stable phase into a reaction flask; stirring uniformly; continuously transferring the oily monomer into a reaction bottle, heating the system to 65 ℃ under stirring at 180rpm, and carrying out heat preservation reaction for 18 hours; after the reaction is finished, cooling to room temperature, filtering by using filter cloth, and respectively washing by using 10 times of ethanol and deionized water to obtain the hydrophilic polyacrylate crosslinked microspheres with the average particle size of 64.2 microns.
EXAMPLE five
A preparation method of hydrophilic polyacrylate crosslinked microspheres comprises the following steps:
(1) amination of the comonomer:
weighing 10g of monomer glycidyl acrylate in a round bottom reaction bottle, adding 2g of dimethyl sulfoxide and 3g of butanediamine, uniformly stirring, heating to 50 ℃, and reacting for 8 hours; after the reaction is finished, obtaining an amination monomer for later use;
(2) preparation of hydrophilic comonomer:
transferring the aminated monomer in the step (1) to a reaction bottle, adding a solvent dimethyl sulfoxide, uniformly stirring, adding 6.2g of glucolactone, heating to 50 ℃, and reacting for 8 hours; after the reaction is finished, hydrophilic comonomer is obtained;
(3) preparation of the stable phase:
weighing 25g of deionized water into a reaction bottle, continuously adding 1.8g of polyvinylpyrrolidone, heating to 80 ℃, and stirring until the polyvinylpyrrolidone is completely dissolved for later use.
(4) Polymerisation
Transferring the hydrophilic comonomer obtained in the step (2) into a beaker, weighing 4.2g of triethylene glycol dimethacrylate, 7.4g of toluene and 0.12g of azobisisobutylnitrile into the beaker, and stirring until the azobisisobutylnitrile is completely dissolved; weighing 1.47g of sodium chloride and 0.06g of sodium p-nitrophenolate in a beaker, adding 200g of deionized water, adding 0.4g of triton X-104, stirring until the sodium chloride is completely dissolved, and transferring the mixture into a reaction bottle; transferring the stable phase into a reaction flask; stirring uniformly; continuously transferring the oily monomer into a reaction bottle, heating the system to 65 ℃ under stirring at 160rpm, and carrying out heat preservation reaction for 18 hours; after the reaction is finished, cooling to room temperature, filtering by using filter cloth, and respectively washing by using 10 times of ethanol and deionized water to obtain the hydrophilic polyacrylate crosslinked microspheres with the average particle size of 58.6 mu m.
EXAMPLE six
A preparation method of hydrophilic polyacrylate crosslinked microspheres comprises the following steps:
(1) amination of the comonomer:
weighing 10g of monomer glycidyl acrylate in a round bottom reaction bottle, adding 2g of dimethyl sulfoxide and 3g of butanediamine, uniformly stirring, heating to 50 ℃, and reacting for 8 hours; after the reaction is finished, obtaining an amination monomer for later use;
(2) preparation of hydrophilic comonomer:
transferring the aminated monomer in the step (1) to a reaction bottle, adding a solvent dimethyl sulfoxide, uniformly stirring, adding 6.2g of glucolactone, heating to 50 ℃, and reacting for 8 hours; after the reaction is finished, hydrophilic comonomer is obtained;
(3) preparation of the stable phase:
weighing 25g of deionized water in a reaction bottle, continuously adding 1.5g of polyvinylpyrrolidone and 0.3g of hydroxyapatite, heating to 80 ℃, stirring until the polyvinylpyrrolidone is completely dissolved and the hydroxyapatite is uniformly dispersed for later use.
(4) Polymerisation
Transferring the hydrophilic comonomer obtained in the step (2) into a beaker, weighing 5.8g of pentaerythritol triacrylate, 14.4g of isobutanol and 0.1g of azobisisobutylnitrile into the beaker, and stirring until the azobisisobutylnitrile is completely dissolved; weighing 1.54g of sodium chloride and 0.04g of sodium nitrite in a beaker, adding 200g of deionized water, adding 0.29g of triton X-104, stirring until the sodium chloride is completely dissolved, and transferring the mixture into a reaction bottle; transferring the stable phase into a reaction flask; stirring uniformly; continuously transferring the oily monomer into a reaction bottle, heating the system to 75 ℃ under the stirring speed of 120rpm, and carrying out heat preservation reaction for 18 hours; after the reaction is finished, cooling to room temperature, filtering by using filter cloth, and respectively washing by using 10 times of ethanol and deionized water to obtain the hydrophilic polyacrylate crosslinked microspheres with the average particle size of 64.1 mu m.
EXAMPLE seven
A preparation method of hydrophilic polyacrylate crosslinked microspheres comprises the following steps:
(1) amination of the comonomer:
weighing 10g of monomer glycidyl methacrylate in a round bottom reaction bottle, adding 2g of dimethyl sulfoxide and 4g of butanediamine, uniformly stirring, heating to 50 ℃, and reacting for 7 hours; after the reaction is finished, obtaining an amination monomer for later use;
(2) preparation of hydrophilic comonomer:
transferring the aminated monomer in the step (1) to a reaction bottle, adding a solvent dimethyl sulfoxide, uniformly stirring, adding 4.2g of gluconolactone, heating to 50 ℃, and reacting for 8 hours; after the reaction is finished, hydrophilic comonomer is obtained;
(3) preparation of the stable phase:
weighing 25g of deionized water in a reaction bottle, continuously adding 2.1g of polyvinylpyrrolidone and 0.3g of hydroxyapatite, heating to 80 ℃, stirring until the polyvinylpyrrolidone is completely dissolved and the hydroxyapatite is uniformly dispersed for later use.
(4) Polymerisation
Transferring the hydrophilic comonomer obtained in the step (2) into a beaker, weighing 8.6g of pentaerythritol triacrylate, 9.4g of phthalic dibutyl ester and 0.1g of azodiisobutyl amidine in the beaker, and stirring until the azodiisobutyl amidine is completely dissolved; weighing 2.71g of sodium chloride and 0.04g of sodium nitrite in a beaker, adding 200g of deionized water, adding 0.274g of triton X-104, stirring until the sodium chloride is completely dissolved, and transferring the mixture into a reaction bottle; transferring the stable phase into a reaction flask; stirring uniformly; continuously transferring the oily monomer into a reaction bottle, heating the system to 75 ℃ under the stirring speed of 120rpm, and carrying out heat preservation reaction for 18 hours; after the reaction is finished, cooling to room temperature, filtering by using filter cloth, and respectively washing by using 10 times of ethanol and deionized water to obtain the hydrophilic polyacrylate crosslinked microspheres with the average particle size of 84.6 microns.
Example eight
A preparation method of hydrophilic polyacrylate crosslinked microspheres comprises the following steps:
(1) amination of the comonomer:
weighing 6g of monomer glycidyl methacrylate in a round bottom reaction bottle, adding 2g of dimethyl sulfoxide and 3g of butanediamine, uniformly stirring, heating to 50 ℃, and reacting for 7 hours; after the reaction is finished, obtaining an amination monomer for later use;
(2) preparation of hydrophilic comonomer:
transferring the aminated monomer in the step (1) to a reaction bottle, adding a solvent dimethyl sulfoxide, uniformly stirring, adding 4.4g of gluconolactone, heating to 50 ℃, and reacting for 8 hours; after the reaction is finished, hydrophilic comonomer is obtained;
(3) preparation of the stable phase:
weighing 25g of deionized water in a reaction bottle, continuously adding 2.1g of polyvinyl alcohol and 0.5g of hydroxyapatite, heating to 80 ℃, stirring until the polyvinyl alcohol is completely dissolved, and uniformly dispersing the hydroxyapatite for later use.
(4) Polymerisation
Transferring the hydrophilic comonomer obtained in the step (2) into a beaker, weighing 8.6g of diethylene glycol dimethacrylate, 14.4g of n-heptane and 0.06g of benzoyl peroxide into the beaker, and stirring until the benzoyl peroxide is completely dissolved; weighing 1.2g of sodium chloride and 0.04g of sodium nitrite in a beaker, adding 200g of deionized water, adding 0.39g of SDBS, stirring until the sodium chloride is completely dissolved, and transferring the mixture into a reaction bottle; transferring the stable phase into a reaction flask; stirring uniformly; continuously transferring the oily monomer into a reaction bottle, heating the system to 75 ℃ under the stirring speed of 320rpm, and carrying out heat preservation reaction for 18 hours; after the reaction is finished, cooling to room temperature, filtering by using filter cloth, and respectively washing by using 10 times of ethanol and deionized water to obtain the hydrophilic polyacrylate crosslinked microspheres with the average particle size of 36.6 mu m.
Example nine
A preparation method of hydrophilic polyacrylate crosslinked microspheres comprises the following steps:
(1) amination of the comonomer:
weighing 10.2g of monomer glycidyl methacrylate in a round bottom reaction bottle, adding 2g of dimethyl sulfoxide and 3g of hexamethylene diamine, uniformly stirring, heating to 50 ℃, and reacting for 7 hours; after the reaction is finished, obtaining an amination monomer for later use;
(2) preparation of hydrophilic comonomer:
transferring the aminated monomer in the step (1) to a reaction bottle, adding a solvent dimethyl sulfoxide, uniformly stirring, adding 4.4g of gluconolactone, heating to 50 ℃, and reacting for 8 hours; after the reaction is finished, hydrophilic comonomer is obtained;
(3) preparation of the stable phase:
weighing 25g of deionized water in a reaction bottle, continuously adding 2.1g of polyvinyl alcohol, heating to 80 ℃, and stirring until the polyvinyl alcohol is completely dissolved for later use.
(4) Polymerisation
Transferring the hydrophilic comonomer obtained in the step (2) into a beaker, weighing 4.6g of diethylene glycol dimethacrylate, 14.8g of dibutyl phthalate and 0.07g of benzoyl peroxide into the beaker, and stirring until the benzoyl peroxide is completely dissolved; weighing 1.4g of sodium chloride and 0.04g of sodium nitrite in a beaker, adding 200g of deionized water, adding 0.7g of triton X-104, stirring until the sodium chloride is completely dissolved, and transferring the mixture into a reaction bottle; transferring the stable phase into a reaction flask; stirring uniformly; continuously transferring the oily monomer into a reaction bottle, heating the system to 75 ℃ under the stirring speed of 560rpm, and carrying out heat preservation reaction for 18 h; after the reaction is finished, cooling to room temperature, filtering by using filter cloth, and respectively washing by using 10 times of ethanol and deionized water to obtain the hydrophilic polyacrylate crosslinked microspheres with the average particle size of 11.2 mu m.
Claims (6)
1. A preparation method of hydrophilic polyacrylate crosslinked microspheres is characterized by comprising the following steps: the method comprises the following steps:
(1) amination of the comonomer: weighing a proper amount of monomer M1 into a round bottom reaction bottle, adding a proper amount of solvents S1 and A1, uniformly stirring, heating to 40-100 ℃, and reacting for 0.5-8 h; after the reaction is finished, obtaining an amination monomer for later use;
(2) preparation of hydrophilic comonomer: transferring the aminated monomer in the step (1) into a reaction bottle, adding a solvent S2, uniformly stirring, adding a proper amount of glucolactone, heating to 40-100 ℃, and reacting for 0.5-8 h; after the reaction is finished, obtaining a hydrophilic comonomer M2;
(3) preparation of the stable phase: adding a proper amount of stabilizer P1 into deionized water, heating to 50-80 ℃, and obtaining an aqueous phase solution containing stabilizer P1 after the stabilizer is completely dissolved;
(4) polymerization: weighing a proper amount of polymerizable monomers M2, M3, a pore-forming agent P2 and an initiator I1 in a beaker, and uniformly mixing for later use; weighing a proper amount of S3 and a proper amount of polymerization inhibitor Z1 in a beaker, adding deionized water, and completely dissolving; adding an emulsifier S4, uniformly dispersing, and transferring to a reaction bottle; transferring the stable phase obtained in (3) to a reaction flask; stirring uniformly; transferring oily solution containing M2, M3, P3 and I1 into a reaction bottle, heating to 65-90 ℃ at the stirring speed of 50-1000rpm, and carrying out heat preservation reaction for 8-18 h; after the reaction is finished, cooling to room temperature, filtering reaction liquid, and sequentially cleaning with methanol or ethanol or acetone and deionized water to obtain the hydrophilic polyacrylate crosslinked microspheres with a large number of hydroxyl groups on the surfaces.
2. The method for preparing hydrophilic polyacrylate crosslinked microspheres according to claim 1, wherein the method comprises the following steps: the monomer M1 in the step (1) is any one or a mixture of glycidyl methacrylate and glycidyl acrylate; s1 is any one or two of methanol, ethanol, dioxane and dimethyl sulfoxide; a1 is one or two of ethylenediamine, propylenediamine, butylenediamine, pentylenediamine, hexylenediamine, octylenediamine, diethylenetriamine, triethylenetetramine and tetraethylenepentamine; in the step (2), the solvent S2 is any one or a mixture of dioxane and dimethyl sulfoxide; the P1 in the step (3) is any one or a mixture of more than two of polyvinyl alcohol, polyethylene glycol, polyvinylpyrrolidone, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, beta-cyclodextrin, beta-methyl cyclodextrin and hydroxyapatite; m3 in the step (4) is any one or a mixture of more than two of divinylbenzene, dipropylene benzene, ethylene glycol dimethacrylate, triethylene glycol, trimethylolpropane trimethacrylate, pentaerythritol triacrylate, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, 1, 3-butanediol dimethacrylate, 1, 4-butanediol dimethacrylate hexamethylene dimethacrylate, divinylphenyl methane, glyceryl trimethacrylate and methylene acrylamide; the P2 in the step (4) is any one or a mixture of more than two of toluene, isobutanol, cyclohexanol, n-hexane, n-heptane, dodecanol, dimethyl phthalate and dibutyl phthalate; i1 in the step (4) is any one or a mixture of more than two of benzoyl peroxide, azobisisobutyronitrile, dimethyl azobisisobutyrate and azobisisobutylamidine; s3 in the step (4) is any one or a mixture of more than two of sodium chloride, sodium sulfate, sodium nitrate, sodium phosphate, sodium hydrogen phosphate and sodium dihydrogen phosphate. The emulsifier S4 in the step (4) is one or a mixture of an ionic emulsifier and a non-ionic emulsifier in any ratio. The ionic emulsifier is alkylbenzene sulfonate, alkyl succinate sulfonate or alkyl diphenyl ether sulfonate.
3. The method for preparing hydrophilic polyacrylate crosslinked microspheres according to claim 1, wherein the method comprises the following steps: in the step (1), the mass ratio of the monomer A1 to the monomer M1 to the monomer S1 is (0.5-5) to (10) to (2-10). In the step (2), the mass ratio of the aminated monomer to the gluconolactone to the solvent S2 is 1: 0.5-30: 20-80. The mass ratio of the stabilizer P1 to the water in the step (3) is 0.5-5: 100. In the step (4), the mass ratio of I1 to M2 to M3 to P2 is (0.5-2) to (2-80) to 100 to (2-200). The mass ratio of the S3 to the water in the step (4) is 5-20: 100. The mass ratio of the oil phase to the water in the step (4) is 5-30: 100.
4. The method for preparing hydrophilic polyacrylate crosslinked microspheres according to claim 1, wherein the method comprises the following steps: the temperature in the step (1) is 30-100 ℃, and the time is 0.5-8 h.
5. The method for preparing hydrophilic polyacrylate crosslinked microspheres according to claim 1, wherein the method comprises the following steps: the stirring speed in the step (4) is 50-1000rpm, the temperature is 65-90 ℃, and the time is 6-24 h.
6. The method for preparing hydrophilic polyacrylate crosslinked microspheres according to claim 1, wherein the particle size of the obtained microspheres is as follows: 0.5um to 200 um.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111566182.5A CN114213581A (en) | 2021-12-20 | 2021-12-20 | Preparation method of hydrophilic polyacrylate crosslinked microspheres |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111566182.5A CN114213581A (en) | 2021-12-20 | 2021-12-20 | Preparation method of hydrophilic polyacrylate crosslinked microspheres |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114213581A true CN114213581A (en) | 2022-03-22 |
Family
ID=80704474
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111566182.5A Pending CN114213581A (en) | 2021-12-20 | 2021-12-20 | Preparation method of hydrophilic polyacrylate crosslinked microspheres |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114213581A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117164902A (en) * | 2023-11-02 | 2023-12-05 | 凯莱英生命科学技术(天津)有限公司 | Hydrophilic polystyrene microsphere and preparation method thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4415700A (en) * | 1980-12-23 | 1983-11-15 | Boehringer Mannheim Gmbh | Hydrophilic latex particles and use thereof |
| CN104941611A (en) * | 2015-06-02 | 2015-09-30 | 浙江大学 | Preparation method of novel grafting high-capacity dendrimer ion chromatography stationary phase stuffing |
| CN105478094A (en) * | 2015-12-25 | 2016-04-13 | 四川大学 | Aminated poly-glycidyl methacrylate crosslinked composite microsphere and preparation method as well as application thereof |
| CN106905533A (en) * | 2017-02-24 | 2017-06-30 | 同济大学 | A kind of method that utilization High Internal Phase Emulsion masterplate method prepares the porous adsorbing material of surface beta cyclodextrin modification |
| CN107177031A (en) * | 2017-04-17 | 2017-09-19 | 烟台大学 | A kind of GMA modified amine curing agent and resist sagging coating |
| CN107365422A (en) * | 2016-05-11 | 2017-11-21 | 中国科学院过程工程研究所 | The hydrophilic modification method and modified resulting materials of poly (glycidyl methacrylate) class or its copolymer |
-
2021
- 2021-12-20 CN CN202111566182.5A patent/CN114213581A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4415700A (en) * | 1980-12-23 | 1983-11-15 | Boehringer Mannheim Gmbh | Hydrophilic latex particles and use thereof |
| CN104941611A (en) * | 2015-06-02 | 2015-09-30 | 浙江大学 | Preparation method of novel grafting high-capacity dendrimer ion chromatography stationary phase stuffing |
| CN105478094A (en) * | 2015-12-25 | 2016-04-13 | 四川大学 | Aminated poly-glycidyl methacrylate crosslinked composite microsphere and preparation method as well as application thereof |
| CN107365422A (en) * | 2016-05-11 | 2017-11-21 | 中国科学院过程工程研究所 | The hydrophilic modification method and modified resulting materials of poly (glycidyl methacrylate) class or its copolymer |
| CN106905533A (en) * | 2017-02-24 | 2017-06-30 | 同济大学 | A kind of method that utilization High Internal Phase Emulsion masterplate method prepares the porous adsorbing material of surface beta cyclodextrin modification |
| CN107177031A (en) * | 2017-04-17 | 2017-09-19 | 烟台大学 | A kind of GMA modified amine curing agent and resist sagging coating |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117164902A (en) * | 2023-11-02 | 2023-12-05 | 凯莱英生命科学技术(天津)有限公司 | Hydrophilic polystyrene microsphere and preparation method thereof |
| CN117164902B (en) * | 2023-11-02 | 2024-01-26 | 凯莱英生命科学技术(天津)有限公司 | Hydrophilic polystyrene microsphere and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4772635A (en) | Bead-shaped crosslinked copolymers containing epoxide groups and basic amino groups, a process for their preparation and their use | |
| KR101297282B1 (en) | Novel packing material with excellent hydrophilicity and process for producing the same | |
| US5114577A (en) | Composite separating agent | |
| US4118347A (en) | Filler for liquid chromatography | |
| EP0626976B1 (en) | Preparation of surface-functional polymer particles | |
| JP2008232764A (en) | Novel filler for filled bed and use therefor | |
| JPH0198606A (en) | Polymer particle and preparation thereof | |
| CN114213581A (en) | Preparation method of hydrophilic polyacrylate crosslinked microspheres | |
| CN112724321A (en) | Boric acid functionalized monodisperse porous microsphere and preparation method and application thereof | |
| CN1045610C (en) | Prepn. of Liquid-phase chromatography-use graininess single dispersion, large hole cross-linked polystyrene microballs | |
| CN106565908B (en) | A kind of preparation method of monodispersed large grain-size polymer microballoon | |
| US5254634A (en) | Crosslinked copolymer particles and process for producing the same | |
| JPH01262468A (en) | Carrier for chromatography | |
| US6362245B1 (en) | Porous co-polymer particles, process for preparing the same and use of the same | |
| JPH07171389A (en) | Manufacture of separating agent | |
| JP3096097B2 (en) | Crosslinked copolymer particles and method for producing the same | |
| CN114634596A (en) | Preparation method of polyacrylate polymer microspheres | |
| EP3495040A1 (en) | Porous materials, method for producing same and uses thereof | |
| JP2890481B2 (en) | Method for producing hydrophilic crosslinked copolymer particles | |
| EP0990667B1 (en) | Porous copolymer particles, process for preparing the same and use of the same | |
| EP3270155B1 (en) | Packing material for liquid chromatography | |
| JP3487665B2 (en) | Method for producing polymer fine particles | |
| JPH1183825A (en) | Separating agent and separation method using it | |
| JP2604339B2 (en) | Hydrophilic gel fine particles and method for producing the same | |
| JP2767251B2 (en) | Composite separating agent and method for producing the same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20220322 |
|
| WD01 | Invention patent application deemed withdrawn after publication |