1. Field of the Invention
The present invention relates to a porous cellulose gel containing crosslinked cellulose particles as a base material, and a method for producing the same. More specifically, the invention relates to a porous cellulose gel that is favorably used as a filler for chromatography.
2. Background Art
A porous cellulose gel contains cellulose particles having a solvent filled in a network structure of cellulose molecules of the cellulose gel, and is highly appreciated as being useful as a filler for various kinds of chromatography. In recent years, protein preparations represented by antibody drugs are improved in productivity through mass fermentation and high fermentation titer, and associated thereto, improvement in productivity is also demanded in purifying process including chromatography and the like. However, a conventional porous cellulose gel is poor in strength and is liable to suffer consolidation of particles in a column, which brings about practical difficulty in use at a high flow rate. Accordingly, such attempts have been made that a cellulose gel is improved in strength by subjecting to a crosslinking treatment.
Various methods have been known for crosslinking cellulose particles, and a method of acting a crosslinking agent in the presence of an alkaline substance is ordinarily employed owing to easiness in crosslinking operation, stability of crosslinked part after crosslinking, and nonionicity of cellulose particles. For example, Japanese Patent No. Sho 43-10059 discloses such a method that powder of cellulose particles is treated with a sodium hydroxide solution to form alkali cellulose, which is then treated with epichlorohydrin. In the method, however, the crystalline structure of the cellulose particles is broken, whereby the mechanical strength of the particles is significantly deteriorated.
As a crosslinking method of an agarose gel, Japanese National-Phase PCT Laid-Open Patent Publication No. 2000-508361 discloses that after reacting agarose with an epoxy group of allyl glycidyl ether to form a gel, an allyl group of allyl glycidyl ether is activated and crosslinked with the polysaccharide, so as to improve the mechanical strength of the crosslinked agarose gel. Japanese Laid-Open Patent Publication No. Sho 60-39558 discloses that an agarose gel is crosslinked with a bifunctional or polyfunctional crosslinking agent having a chain length of from 6 to 12 in the first step, and then crosslinked with a bifunctional crosslinking agent having a chain length of from 2 to 5 in the second step, whereby the mechanical strength of the crosslinked agarose gel can be improved.
However, such a method has not yet been known that a cellulose gel is improved in mechanical strength in an extent that sufficiently resolves the problems in the production process of protein drugs.