Chromatographic separation process and chromatographic...

Liquid purification or separation – Processes – Chromatography

Reexamination Certificate

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C210S198200, C127S046200

Reexamination Certificate

active

06409922

ABSTRACT:

REFERENCE TO RELATED APPLICATIONS
This application is a 371 of PCT/JP98/05842 filed Dec. 24, 1998.
1. Technical Field
The present invention relates to a chromatographic separation process and a chromatographic separator, and more particularly to a chromatographic separation process for separating a starting fluid material containing at least 3 components into at least 3 fractions in a plurality of steps with a chromatographic separator packed with an ion exchanger as at least part of chromatographic packing and a chromatographic separator not only effectively usable for the above-mentioned chromatographic separation process but also usable for a variety of other processes.
2. Background Art
There are various conventional methods of chromatographic separation of a starting fluid material containing at least 3 components into the respective components, representative examples of which include the following methods:
A method (1) is a batchwise one wherein analytical high-performance liquid chromatography is scaled up, and which is generally called preparatory chromatography.
A method (2) is one using either 2 simulated moving bed chromatographic separators for separation of only 2 components or using such a chromatographic separator twice as disclosed in Japanese Patent Laid-Open No. 124,895/1990. More specifically, a starting material is either first separated into a component A and a mixture of components B+C, followed by separation of the mixture of components B+C into the components B and C, or first separated into a mixture of components A+B and the component C, followed by separation of the mixture of components A+B into the components A and B. This is so because separation of only 2 components is possible with an ordinary simulated moving bed chromatographic separator. Thus, in order to actually separate 3 components from one another, either 2 simulated moving bed chromatographic separators must be prepared or one such separator must be used twice. In the latter case, a solution midway of separation (fraction of mixture) must be stored once, and then subjected to separation under varied conditions while using the same separator again.
A method (3) is one disclosed in Japanese Patent Laid-Open No. 227,804/1992, wherein one improved simulated moving bed chromatographic separator packed with one packing is used to efficiently and continuously separate a fluid mixture containing at least 3 components into fractions enriched with the respective components. Herein, the term “enriched with components” refers to solids-based concentration (enrichment) of components to be separated (components desired to be separated) in the respective fractions separated in the direction of fluid flow. Thus, the degree of enrichment is correlated with purity and recovery.
A method (4) is one disclosed in Japanese Patent Laid-Open No. 80,409/1989, wherein separation columns (packed column units having packing bed units) packed with a first packing having the following partition coefficients for components: component A<component B<component C are arrayed alternately and used together with separation columns packed with a second packing having the following partition coefficients for components: component A<component C<component B.
The methods (2), (3) and (4) are fundamentally those whereto application is made either of a basic simulated moving bed procedure comprising an operation of feeding a starting fluid material containing a plurality of components to be separated and desorbent (called “eluent” in the case of liquid) at respective designated positions to an endless circulation system (loop) made up of a plurality of packing bed units packed with chromatographic packing (sorbent) and linked endlessly to flow the starting fluid material and the desorbent in one direction through the endless circulation system, and withdrawing fractions from zones enriched with respective components out of the endless circulation system while taking advantage of a phenomenon that a plurality of components to be separated are separated into respective zones enriched with the respective components due to a difference between the components in affinity for chromatographic packing, and an operation of intermittently displacing the starting fluid material and desorbent feed positions as well as the fraction withdrawal positions in the direction of fluid flow as if the chromatographic packing were apparently moved in the direction opposite to that of fluid flow, whereby two fractions enriched with the respective components are continuously obtained from the starting fluid material; or of an improved or altered procedure based on the basic simulated moving bed procedure (in the present invention, the “simulated moving bed procedure” is defined as encompassing such improved or altered ones as well).
Although the foregoing methods all belong to the same technology in respect of chromatographic separation of a starting fluid material containing at least 3 components into at least 3 fractions, they involve the following respective demerits when they are adopted in industrial-scale equipment for carrying out the separation technology.
The method (1) is poor in separation because it is batchwise, and is often unfit for industrial-scale separation involving treatment of a large amount of starting liquid material because the amount of eluent to be used must inevitably be large.
The method (2) requires either installing 2 simulated moving bed chromatographic separators or using the same separator twice. Where 2 simulated moving bed chromatographic separators are installed, the equipment cost is increased. Where the same separator is used twice, the same packing must inevitably be used because replacing chromatographic packing every time is troublesome in an aspect of operation. This involves a problem that all 3 components cannot efficiently be separated from one another in some cases because one kind of packing is used. For example, there arises a case where a component A is too well separated from a component B, but separation of the component B from a component C is so poor that it is difficult to heighten the component purities of all fractions.
The method (3) also sometimes fails in efficient and distinct separation of all 3 components because one kind of packing is used. For example, there arises a case where a component A is too well separated from a component B, but separation of the component B from a component C is so poor that it is difficult to heighten the component purities of all fractions.
The method (4) involves a difficulty in combining 2 kinds of suitable packings for a starting solution to be subjected to chromatographic separation.
Accordingly, in the foregoing methods (2), (3) and (4), the separability of components [relevant to the load (feed rate) of a starting fluid material], the purities and recoveries of components contained as objects of separation in recovered fractions, the amount of used desorbent relevant to concentration energy involved in concentrating recovered fractions (relevant to the desired component concentrations of the recovered fractions), etc. are influenced by packing(s) packed in packing bed units, while involving a problem that a countermeasure for an improvement in respect of one of those influences tends to produce other adverse effects.
Although it can be said that choice and use of the optimum packing capable of suitably adjusting the foregoing various influences will suffice in order to solve such a problem, choice of the optimum packing is not easy as a matter of fact. For example, when the resolution, by packing, of components contained in a starting fluid material is enhanced as much as possible in order to heighten the purities and recoveries of components as objects of recovery, intervals between a plurality of zones enriched with respective components are spread too broad in the endless circulation system, whereby the amount of desorbent to be used is increased (the amount of desorbent to be used for desorption of a strong-affi

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