Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1991-12-30
1993-09-14
Nutter, Nathan M.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
536 57, 536 84, 536 92, 536 98, 525 5421, 525 541, 530403, 530404, 530405, 530814, 436530, C08B 330
Patent
active
052450244
DESCRIPTION:
BRIEF SUMMARY
This invention relates to an improved uncrosslinked cellulose chromatography support and, in particular, to a support comprising substantially spherical, high density cellulose particles. This invention also relates to a method of making such substantially spherical, high density cellulose particles and, in particular, to a method for making spherical cellulose particles from viscose in a stable emulsion of a liquid carrier and emulsifying agents.
BACKGROUND OF THE INVENTION
Cellulose and cellulose derivatives have been used as chromatographic supports and as polymeric carriers. General chromatographic uses include analytical and preparative column chromatography, thin layer chromatography, ion exchange, gel chromatography and chelation and affinity sorbents. In addition, cellulose particles may be used as fillers and bulking agents in pharmaceuticals, cosmetics, and food products. Although natural abundance and availability, coupled with a variety of known derivatization schemes, make cellulose an attractive chromatographic support, it has generally suffered from several disadvantages. The most notable disadvantages are mechanical instability and poor flow characteristics.
Cellulose is a naturally occurring polymer made of linked glucose monomers. In the native state, adjacent polymeric glucose chains are extensively hydrogen bonded in some regions and less hydrogen bonded in others. The regions of relatively high hydrogen bonding are generally referred to as "microcrystalline regions" while the less hydrogen bonded regions are referred to as amorphous regions. For chromatographic applications, it is generally desirable to limit the amorphous regions, and to utilize cellulose having either a fibrous or a microgranular form. Such fibrous and microgranular materials are generally prepared by limited acid hydrolysis of bulk cellulose which results in the preferential loss of interchain amorphous regions and increases the microcrystalline regions. Both fibrous and microgranular cellulose compositions are generally referred to as microcrystalline cellulose.
Procedures typically used to prepare microcrystalline cellulose generally result in aggregated particles which require grinding and particle size separation to yield materials suitable for chromatographic purposes. Further, the individual microcrystalline cellulose particles are relatively irregularly shaped and fragile. These features adversely effect the use of these types of materials as chromatographic beds or columns because microcrystalline cellulose tends to easily clog and compact. In addition, these materials tend to break down and generate fines when subject to elevated pressure. These drawbacks can result in unacceptable flow characteristics and poor chromatographic separations.
The use of cellulose in the form of crosslinked beads or spherical particles may partially overcome the poor flow characteristics of microcrystalline cellulose chromatographic supports. When cellulose is made into beads using known procedures, however, the porosity of the cellulose particles and their wide range of sizes cause the beads to be subject to mechanical breakdown when used in packed beds or columns. Although, mechanical stability may be improved by the addition of cross linking agents, these crosslinking agents may increase the expense of the support, complicate the manufacturing processes and limit the general applicability of use of the support.
Further, when placed in aqueous solutions, porous cellulose particles typically swell significantly. Swelled, porous cellulose beads suffer from sensitivity to changing ionic strengths in eluting buffers and solvents. As a result, conventional, swellable cellulose supports must therefore be used within a specified narrow range of ionic strengths. If this specific range of ionic strengths is exceeded, the swelled cellulose particles compact or shrink which results in very poor flow characteristics and leads to either poor chromatographic separation or to no separation at all.
Several methods of preparing spherical c
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Beavins Anita
Scarpa Ioannis
Loyola University of Chicago
Nutter Nathan M.
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