Method for producing polymer particles, and polymer particles
Provided are polymer particles which can be used at a high flow rate when used as a filler for chromatography, that is, has excellent resistance flow rate appropriate for processing in large quantities, and also has a high binding capacity for target molecules such as proteins when an appropriate ligand is contained in the particles, and a method for producing the polymer particles; specifically, crosslinked polymer particles and a method for producing the crosslinked polymer particles, polysaccharide composite particles and a method for producing the polysaccharide composite particles, a filler for chromatography using the polymer particles, and an adsorbent for antibody purification. Disclosed are: A. a method for producing polysaccharide composite particles, the method including the following steps (1) to (3): (1) a step of preparing a polysaccharide solution, in which two or more kinds of polysaccharides are dissolved in an ionic liquid; (2) a step of preparing a droplet dispersion liquid of the polysaccharide solution, in which liquid droplets of the polysaccharide solution are dispersed in an organic solvent having low compatibility with the ionic liquid; and (3) a coagulation step in which a composite of the polysaccharides are coagulated to obtain the polysaccharide composite particles; and B. a method for producing a crosslinked polymer particle, the method including a step of allowing a polymer dissolved in an ionic liquid, to react with a crosslinking agent while the polymer is subjected to droplet dispersion in an organic solvent having low compatibility with the ionic liquid.
1. A method for producing a polysaccharide composite particle, the method comprising:
dissolving two or more kinds of polysaccharides in an ionic liquid, thereby preparing a polysaccharide solution;
dispersing liquid droplets of the polysaccharide solution in an organic solvent having low compatibility with the ionic liquid, thereby preparing a droplet dispersion liquid of the polysaccharide solution; and
coagulating a composite of the polysaccharides, thereby obtaining the polysaccharide composite particle.
2. The method according to claim 1 , wherein the polysaccharides are two or more selected from the group consisting of cellulose, agarose, pullulan, and dextran.
3. The method according to claim 1 , wherein at least one of the polysaccharides is cellulose.
4. The method according to claim 1 , wherein the ionic liquid is an alkylimidazolium salt.
5. The method according to claim 1 , wherein the ionic liquid is 1-ethyl-3-methylimidazolium acetate, 1-butyl-3-methylimidazolium chloride, or a mixture thereof.
6. The method according to claim 1 , wherein the dispersing is carried out by mixing a solution comprising the organic solvent and an oleophilic polymer, with the polysaccharide solution.
7. A polysaccharide composite particle produced by the method according to claim 1 .
8. The polysaccharide composite particle according to claim 7 , wherein a linear flow rate at a column pressure of 0.4 MPa, when polysaccharide composite particles are packed in a column with an inner diameter of 0.5 cm to a height of 20.0 cm and water at 25° C. is allowed to flow through, is from 1600 cm/hour to 6000 cm/hour.
9. A filler; comprising:
the polysaccharide composite particle according to claim 7 ,
wherein the filler is suitable for chromatography.
10. An adsorbent comprising:
the polysaccharide composite particle according to claim 7 ,
wherein the adsorbent is suitable for purifying an antibody.
11. The adsorbent according to claim 10 , wherein the adsorbent comprises Protein A as an affinity ligand.
12. A method for producing a crosslinked polymer particle, the method comprising:
allowing a polymer dissolved in an ionic liquid, thereby reacting with a crosslinking agent while subjecting the polymer to droplet dispersion in an organic solvent having low compatibility with the ionic liquid.
13. The method according to claim 12 , further comprising:
adding a medium to a dispersion liquid,
wherein the medium is compatible with the ionic liquid and does not substantially dissolve the polymer to coagulate liquid droplets.
14. The method according to claim 12 , wherein the polymer is at least one member selected from the group consisting of a polysaccharide and a derivative thereof.
15. The method according to claim 14 , wherein the polysaccharide is at least one member selected from the group consisting of cellulose, agarose, chitosan, dextran, pullulan, and a derivative thereof.
16. The method according to claim 15 , wherein the polysaccharide comprises at least cellulose or a derivative thereof.
17. The method according to claim 12 , wherein the crosslinking agent is at least one member selected from the group consisting of a halohydrin, a bisepoxide, a polyepoxide, and divinylsulfone.
18. A crosslinked polymer particle produced by the method according to claim 12 .
19. The crosslinked polymer particle according to claim 18 , wherein a linear flow rate at a column pressure of 0.4 MPa, when crosslinked polymer particles are packed in a column with an inner diameter of 0.5 cm to a height of 20.0 cm and water at 25° C. is allowed to flow through, is from 1600 cm/hour to 6000 cm/hour.
20. A filler, comprising:
the crosslinked polymer particle according to claim 18 ,
wherein the filler is suitable for chromatography.
21. An adsorbent, comprising:
the crosslinked polymer particle according to claim 18 ,
wherein the adsorbent is suitable for purifying an antibody.
22. The adsorbent according to claim 21 , wherein the adsorbent comprises Protein A as an affinity ligand.