JPH11267404A - Chromatographic separating method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To efficiently separate each component in a fluid containing a medium affinity component by making a packing material with which the fluid is brought in contact in the state that a first packing material having a large separation degree of the medium affinity component and a small affinity component and a second packing material having a large separation degree of a large affinity component and the medium component coexist and adjusting the separation degree. SOLUTION: In a first process, a cut-off valve Z is closed and a fluid raw material supply valve f is opened. While a fluid raw material F is supplied through the supply valve f from the top of a unit packed tower 5 in a sorption band rich in an A component, the A fraction is discharged from the bottom of a unit packed tower 8 in the downstream side from a raw material supply position. At a same time, a desorbing agent supply valve 1D is opened and while a desorbing agent D is supplied from the top of a packed tower 1 in the upstream side from a packed tower 5 in a sorption band rich in a B component, the B fraction is discharged from the bottom of the packed tower 5. In a second process, each residual component of A and C fraction is discharged from the packed towers in the sorption band rich in the residual components in the first process. The discharging position of the each fraction is moved to the packed towers in the downstream side of the system coinciding with the movement of the sorption band. Thus, the adjustment of the separation degree and the recovery rate of the objective material can be increased.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a chromatographic separation method, and more particularly to a chromatographic separation method for separating a fluid raw material containing three or more components into three or more fractions.

[0002]

2. Description of the Related Art There are various conventional methods for chromatographic separation of each component from a raw material fluid containing three or more components, and several typical examples thereof are as follows.

The first method is a batch method in which high-performance liquid chromatography for analysis is scaled up, and is generally called a preparative chromatographic separation method.

A second method is a method disclosed in Japanese Patent Application Laid-Open No. 2-124895, in which a simulated moving bed type chromatographic separation apparatus for separating only two components is used two times or twice. That is, first, the raw material is separated into the A component and the B + C component mixture, and then the B + C component mixture is separated into the B component and the C component, or the A + B component mixture and the C component are first separated, and then the A + B component is separated. The component mixture is separated into component A and component B. This is because an ordinary simulated moving bed type chromatographic separation apparatus can only separate two components, and in order to actually separate three components, two simulated moving bed type chromatographic separation apparatuses are prepared or a one-series apparatus. 2
In the latter case, the liquid during the separation (fraction of the mixture) must be stored once, and the same apparatus must be used again under different conditions.

A third method is a method disclosed in Japanese Patent Application Laid-Open No. Hei 4-227804, in which one type of improved simulated moving bed type chromatographic separation apparatus is filled with one kind of filler,
The process of extracting the fraction enriched in components with intermediate affinity to the filler while supplying the desorbent and the raw material fluid, and the enrichment in components with low affinity and high affinity for the filler while supplying the desorbent By repeating the step of extracting each of the fractions obtained from the raw material fluid containing three or more components,
It is intended to efficiently and continuously separate fractions enriched in each component. Here, “component enrichment” means that the component to be separated (the component to be separated) collects in each of the fractions separated in the flow direction of the fluid, and the degree of enrichment affects the purity and the recovery rate. Correlate.

A fourth method is a method disclosed in Japanese Patent Application Laid-Open No. Hei 7-232003, in which a simulated moving bed apparatus comprising four unit packed beds is filled with one kind of filler, and an eluent and a raw material are added. A step of extracting each fraction enriched in a component having low affinity for the filler and a component having an intermediate affinity with the liquid while supplying the liquid, and circulating the liquid in the simulated moving bed without supplying or extracting the liquid This is a method of separating into three or more fractions by repeating a step of supplying and a step of extracting a fraction enriched in a component having a high affinity for a filler while supplying an eluent.

A fifth method is a method disclosed in JP-A-64-80409, in which a separation column packed with a first filler having a distribution coefficient for each component is A component <B component <C component. (A unit packed tower having a unit packed bed) and a separation tower filled with a second filler having a distribution coefficient of A component <C component <B component are alternately used.

The above second to fifth methods are basically applied to an endless circulation system in which a plurality of unit packed towers filled with a filler (sorbent such as an adsorbent) are connected endlessly. A plurality of components to be separated are charged by supplying a fluid raw material and a desorbent (in the case of liquid, also referred to as an eluent) containing the components to be separated from the respective predetermined positions and flowing in one direction of the endless circulation system. Utilizing the phenomenon that each component is separated into enriched bands due to the difference in affinity (affinity) for the agent,
Filling by extracting the fraction of the zone enriched in each component from the endless circulation system, and intermittently moving the supply position of the fluid raw material and the desorbent and the extraction position of each fraction in the direction of fluid flow A simulated moving bed system in which the agent is apparently moved in a direction opposite to the fluid flow to continuously obtain two fractions in which each component is individually enriched from the fluid raw material. Or a method of improving or modifying the pseudo moving layer method (in the present invention, including the improvement or modification method of the basic pseudo moving layer method, is considered to be a “pseudo moving layer method”).

[0009]

By the way, each of the above methods is a similar technique in that a fluid raw material containing three or more components is chromatographed into three or more fractions.
When such a separation technique is employed in an apparatus that is implemented on an industrial scale, there are the following disadvantages.

[0010] The first method is not suitable for industrial separation in which a large amount of a raw material liquid is treated because the separation is poor because of the batch system and the amount of eluent used is large. There's a problem.

In the second method, it is necessary to install two simulated moving bed type chromatographic separation apparatuses or to use the same apparatus twice. When two simulated moving bed type chromatographic separation apparatuses are installed, there is a problem that the apparatus cost increases. In addition, when the same device is used twice, it is necessary to use the same filler because replacing the filler every time becomes complicated, and all three components are efficiently used because only one filler is used. There is a problem that it may not be able to be separated.
For example, the A component and the B component are separated well enough to be separated too much, but the B component and the C component are poorly separated, and the component purity of each fraction may not be increased.

[0012] In the third and fourth methods, the filler is also 1
There is a problem that all three components cannot be efficiently separated because of the type. For example, the A component and the B component are separated well enough to be separated too much, but the B component and the C component are poorly separated, and the component purity of each fraction may not be increased.

In the fifth method, there is a problem that it is difficult to appropriately combine two kinds of fillers with the stock solution to be separated.

Therefore, in the above-mentioned second to fifth methods, the separation of each component [this is related to the load (supply) amount of the fluid raw material] and the recovery And the amount of desorbent used (related to the concentration of the target component in the recovered fraction), etc., which are affected by the purity and recovery rate of the target component contained in the recovered fraction, and the concentration energy used to concentrate the recovered fraction. However, there is the problem that measures to improve one of these effects tend to worsen the other.

In order to solve such a problem, it may be said that it is sufficient to select and use an optimum filler capable of adjusting the various effects described above conveniently. Selecting the optimal filler is not easy. For example, if the degree of separation of the filler from the plurality of components contained in the fluid raw material is improved as much as possible in order to increase the purity and the recovery rate of the recovery target component, the space between the multiple zones rich in each component in the endless circulation system is reduced. The amount of the desorbing agent is increased due to excessive spread (the affinity of each component with the filler is greatly different from each other, so the amount of the desorbing agent used is particularly large for desorbing a component having a strong affinity. ), Causing a problem that the concentration of each component contained in each fraction to be collected is diluted. Conversely, if a filler having a low degree of separation is used to reduce the amount of the desorbing agent used, This is because a problem that the purity and the recovery rate are reduced is caused. As described above, it is rare that there is an existing filler having an appropriate degree of separation in relation to a plurality of components to be separated, and it is not easy to newly create such a filler. The “separation degree” is an index indicating the degree of separation of two components, and two adjacent enriched fractions (bands)
It is defined as being equal to the value obtained by dividing the distance between the centers of 1 and 2 by the average bandwidth (see "High Performance Liquid Chromatography", published by Tokyo Chemical Dojin, 1976).

The present invention has been made in view of the above-mentioned problems of the prior art method, and efficiently separates each component from a fluid raw material containing three or more components in a chromatographic separation. It is intended to provide a method for separating.

[0017]

As a result of various studies on the above-mentioned conventional methods, the present inventors have solved the problems of the conventional chromatographic separation method and reached the present invention. According to the present invention, in a batch-type or simulated moving-bed type chromatographic separation, for example, while obtaining a target component for separation and recovery with high purity and a high recovery rate, it is a trade-off to obtain the component as high as possible. Requirements can be satisfied at the same time.

[0018] The chromatographic separation method of the present invention that achieves the above-mentioned object, according to a chromatographic separation method in which a fluid raw material containing at least three components is passed through a filler layer and divided into at least three fractions, A fluid containing an intermediate component having an “affinity for a filler” (hereinafter sometimes simply referred to as “affinity”) comes into contact between a position at which a component having an intermediate affinity is extracted from a filler layer from a supply position. The filler having at least a high degree of separation between a component having an intermediate affinity and a component having a low affinity has a high degree of separation between the first filler and a component having a high affinity and a component having an intermediate affinity. Second
Are characterized by being mixed as a combination of the fillers and adjusting the degree of separation of each component.

That is, according to the present invention, a fluid material containing three or more components is passed through a filler layer, and the components having a high affinity to a component having a low affinity for the filler contained in the fluid material have different affinities. A chromatographic separation method for separating three or more components into at least three fractions, wherein the affinity for the filler is at least between the position where the fluid raw material is supplied to the filler layer and the position where the intermediate component is extracted from the filler layer. The filler contacted with a fluid containing a component having an intermediate property is two or more fillers having different degrees of separation for the components, and
A first filler having a high degree of separation between a component having an intermediate affinity for the filler and a component having a low affinity for the filler, at least between a component having an affinity for the filler and a component having a low affinity for the filler; And a component having a high affinity for the filler and a second filler having a high degree of separation between components having an intermediate affinity for the filler are mixed, and the degree of separation of each component is adjusted. To provide a chromatographic separation method.

According to the method of the present invention, the separation of the filler as a whole of the chromatographic separation apparatus at least between the position where the fluid raw material is supplied to the filler layer and the position where the component having an intermediate affinity is extracted from the filler layer. The degree can be adjusted, and the target component can be separated as necessary and sufficiently. In order to facilitate this understanding, the simplest case using two kinds of fillers in three-component separation will be described as a representative example. For example, 3
There are components A, B, and C (A: low affinity, B: medium affinity, C: high affinity), and the first filler has good separation between A and B but has poor separation between B and C. Is expressed as “A-BC”, and the separation between A and B is bad, but the separation between B and C is good.
When the separation state of the filler is expressed as "AB-C", if these fillers are combined at an appropriate ratio to form a mixed state of them, the separation state of "ABC" will be obtained. It has been found that the three components A, B and C can be separated as necessary and sufficiently. Component B and component A
Since the separation of the component B and the component C is a problem, such a mixed state may occur at least between the position where the fluid raw material is supplied to the filler layer and the position where the component having the intermediate affinity is extracted from the filler layer. Good.

As such a filler, for example, among the three components A, B, and C contained in the fluid raw material, for example, the filler and the component B which are more effective by separating the component A and the component B are used. Is a combination of two or more fillers that is more effective for separating the component C and the component C, and as a result of mixing them, the fillers can separate the components as necessary and sufficiently. Any filler may be used. Examples of the filler that can be used in the present invention include an ion exchange resin, zeolite, silica gel, activated carbon, and other natural or synthetic sorbents (such as adsorbents).
In the case of an ion exchanger such as an ion exchange resin or zeolite, the ion form composition may be a mixed ion form of two or more ions. Two or more types of fillers differing in material for the purpose of chromatographic separation from these fillers, or two or more types of fillers having the same material but different ion forms (in the case of ion exchangers) and different internal pore diameters What should be selected from
When an ion exchanger is used as at least one of the two or more fillers in the separation operation of a raw material liquid such as an aqueous liquid as a fluid raw material, the ionic composition of the raw material liquid and the separation treatment liquid substantially changes. It is preferable to perform chromatographic separation under conditions that do not have such a condition, in order to ensure stable separation over time.

In order to adjust the above-mentioned degree of separation, two or more different fillers selected from fillers having different degrees of separation of the components to be separated contained in the fluid raw material (at least having an affinity with a component having an intermediate affinity). In order to create a mixed state of a first filler having a large separation between small components and a second filler having a large separation between a component having a high affinity and a component having an intermediate affinity) As proposed by the present applicant in Japanese Patent Application No. 9-257055, a simple mixed state of two or more different fillers and / or a multi-layered laminated state of the two or more different fillers and / or A plurality of unit filler layers are connected to form a filler layer, and at least one filler among the two or more different fillers is used alone for at least one unit filler layer, and the entire filler layer (at least the filler) From the position where the fluid raw material is supplied to the bed Looking sum resistance intermediate components from the filler layer) between a position withdrawn from the filler layer may be raise, mixed state of two or more different fillers above. When two or more fillers having different degrees of separation are used in a mixed state, the ratio and type of the two are selected based on various experimental results according to the type and purpose of the component to be separated. can do.

Here, "different degree of separation" means, for example,
When two types of packing materials are packed into respective test columns of the same shape at a standard packed bed height (for example, 0.3 to 1 times the actual bed height of the unit packed tower), and actually separated. When the degree of separation is measured for two components to be separated under conditions (temperature, flow rate, etc.), it means that there is a difference in the degree of separation between the two types of fillers. The degree of the difference in the degree of separation may vary depending on the component to be separated, the material of the filler, and the like, but cannot be determined unconditionally, but is generally 0.1 or more, preferably 0.2 or more. It suffices if there is a difference in the degree of separation.

In the present invention, a batch type preparative chromatographic separation method or a simulated moving bed type chromatographic separation method may be used.
Therefore, as the chromatographic separation device, various chromatographic separation devices such as a batch type preparative chromatographic device used in the above-mentioned conventional method, a simulated moving bed type chromatographic separation device having three or more components, and various types thereof. The improved or simplified device can be used as it is.

In a batch type preparative chromatograph, for example, two or more kinds of packing materials (at least a component having an intermediate affinity and a component having a low affinity) having different degrees of separation with respect to the component to be separated are provided in a column. A first filler having a high degree of separation and a second filler having a high degree of separation between a component having a high affinity with a component having a high affinity and a component having a high affinity between the two components). The degree of separation of the filler may be adjusted as a structure or a combination thereof (that is, at least one layer is filled with a mixed filler to form a laminated structure). Further, a filler layer is formed by connecting a plurality of unit filler layers, and
At least one filler of two or more fillers may be independently filled in at least one unit packing layer, and in this case, at least one filler is at least one filler.
It is preferable because the operation of filling, filling, and regenerating and exchanging the two unit filling layers becomes simple. By mixing two or more types of fillers in this way, the degree of separation of three or more components to be separated is appropriately adjusted, and as a result, the amount of desorbing agents such as eluents is small, and a short separation process is realized. In addition, the target component can be obtained with high purity and high recovery.

In the case of a batch-type preparative chromatograph having a laminated structure, for example, two layers are stacked and filled, a fluid material is first flowed from the upstream end of the first layer, and then a desorbent is supplied from the first layer to the first layer. The fraction of the A + B mixture flowing into the second layer is passed through the second layer as it is, separated into an A fraction and a B fraction, and sequentially extracted from the downstream end of the second layer. The C fraction is a first layer and a second layer. It can also be configured to be extracted from the boundary part. In this case, the position of the boundary between the first layer and the second layer is changed by providing a supply port for the desorbent at the boundary between the first layer and the second layer, or by providing a plurality of outlets at the boundary. So that you can do it,
It is also preferable to be able to cope with various operating conditions and various fluid raw materials.

Examples of a simulated moving bed type chromatographic separation apparatus for separating three or more components are described in JP-A-9-132586, JP-A-64-80409, and JP-A-4-227.
No. 804, Japanese Patent Application Laid-Open No. 4-369701, and the like, and further, the devices proposed by the present applicant in Japanese Patent Application No. 9-366256. In addition, in such a simulated moving bed type chromatographic separation apparatus, each unit packed column formed by packing a column with a packing usually has one unit packed bed,
A configuration in which each unit packed tower has two or more unit packed beds partitioned, and each unit packed bed is provided with a raw material supply unit, a desorbent supply unit, and a plurality of fluid fraction extracting units as necessary. It may be.

In a simulated moving bed type chromatographic separation apparatus having three or more components, a first filler having a high degree of separation between a component having an intermediate affinity and a component having a low affinity and a component having a high affinity have a high affinity. As a method of mixing two or more kinds of fillers including at least the second filler having a large degree of separation between the intermediate components, the unit filler may be mixed with the two fillers and then filled. A layer is first filled with a first filler and then a second filler is filled thereon in a layer, or conversely, a second filler is first filled and a first filler is placed thereon in a layer and Alternatively, two or more fillers may be filled in three or more layers (in the case of two kinds of fillers, for example, three or more fillers may be alternately filled). Is a method in which only the first filler is filled and another unit packed layer is filled only with the second filler. Affinity from a position for supplying fluid material to Hama agent layer may be intermediate components in the form of mixing two or more kinds of fillers as a whole apparatus part between a position withdrawn from the filler layer. From the viewpoint of simplicity of actual operation, 2
Preferably, at least one filler of at least one kind of filler is independently filled in at least one unit packed bed, and in this case, at least one filler is filled with at least one filler.
The operation of filling, filling, and regenerating or exchanging the two unit packed layers is simplified. For the same reason, it is needless to say that a system in which a certain unit packing layer is filled with only the first filler and another unit packing layer is filled with only the second filler is more preferable. By mixing two or more types of fillers in this way, the degree of separation of three or more components to be separated is appropriately adjusted, and as a result, the amount of desorbing agents such as eluents is small, and a short separation process is realized. In addition, the target component can be obtained with high purity and high recovery.

When an ion exchanger is used as a filler, as an agent for changing the original ionic form to a desired ionic form, for example, in the case of a cation exchange resin, various acids (to be in H form), Salts and hydroxides of alkali metals and ammonia such as sodium and potassium, or hydroxides thereof, can be converted into a monovalent ion form, and salts of alkaline earth metals such as calcium and magnesium can be used. A hydroxide or the like or a mixture thereof can convert the ionic form into a divalent ionic form. As other agents, there are those capable of converting the ionic form into a trivalent ionic form such as aluminum chloride. An appropriate drug may be selected in relation to the component to be separated. Since a smaller amount of such a drug is more advantageous in terms of cost, time, etc., it is necessary to change the ion form of the minimum necessary amount of ion exchanger or to change the ion form for all ion exchangers. Also,
It is preferable to change the ion form at the minimum necessary ratio ("changed ion form / total ion form ratio" to the ion exchange capacity of the ion exchanger).

In a simulated moving bed type chromatographic separation apparatus using an ion exchanger such as an ion exchange resin, three or more components are separated, and the ion form of a part of the ion exchanger is changed to a desired filler mixed state to obtain a separation degree. If it is necessary to adjust, the affinity for the filler from at least the position where the fluid raw material is supplied to the filler layer is at least one or more between the positions where the intermediate component is extracted from the filler layer, but not all. By changing the ionic form by flowing an aqueous medium solution of a salt, an acid or an alkali into a unit packed tower (or unit packed bed) which is not the same, the separation degree of the entire packed bed between the components to be separated can be easily and appropriately adjusted. May be adjusted. Of course, a part of an ion exchanger such as an ion exchange resin may be transferred to another spare column, and the ion form may be changed in that column. From the viewpoint of actual operation, there is a problem of acid resistance and alkali resistance of the material of the apparatus. Therefore, for example, it is preferable to use an aqueous medium solution of a salt that is more neutral than an acidic or alkaline aqueous medium solution.

The monovalent ion form and the divalent ion form of the strongly acidic cation exchange resin often differ in the degree of separation of various components to be separated. Can be easily changed, so that one of the two or more fillers is a monovalent ion form of a strongly acidic cation exchange resin, and the other is a monovalent ion form of a strongly acidic cation exchange resin.
Preferably, it is in a valence ion form.

For example, in order to separate saccharides, a monovalent ion form (potassium form, sodium form, a mixed form thereof, etc.) or a divalent ion form (calcium form, magnesium form, etc.) of a gel type strongly acidic cation exchange resin are used. And the like, and an appropriate ion form may be selected from these and combined to form a mixed state of two or more fillers. In addition,
As a rule of thumb, monovalent ion-type cation exchange resins are suitable for the separation of monosaccharides from disaccharides and trisaccharides due to differences in molecular weight. For example, an aqueous solution of a salt such as sodium chloride and a cation exchange resin are used. It is desirable to increase the amount of the monovalent ion form by contact, and a divalent ion form cation exchange resin is suitable for separating saccharides having the same molecular weight. It is desirable to increase the amount of the divalent ion form by contact with the resin.

When the ion exchanger is used, for example, for the separation of an aqueous raw material liquid, the method of the present invention is intended to stably maintain a mixed state of two or more fillers and maintain a constant degree of separation. It is preferable to carry out the reaction under such conditions that the ionic form composition of the ion exchanger does not substantially change with the progress of the separation operation. Therefore, in such a case, as described above, it is preferable to perform the chromatographic separation under the condition that the ionic composition of the raw material liquid and the separation treatment liquid does not substantially change.
In the separation of saccharides using an ion-exchange resin, the ion form proceeds in a direction to reach a mixed ion form composition equilibrium with various ions contained in the raw material liquid as the operation proceeds,
Some ions of the ion exchange resin are transferred to the next packed bed (for example,
Unit packing tower), but all ion exchange of all the filler layers at least between the position where the raw material liquid is supplied to the filler layer and the position where the component having an intermediate affinity is extracted from the filler layer As long as at least two types of ion-exchange resins in an amount necessary for the separation are present in a mixed state with respect to the amount of the resin, there is no problem, and the method of the present invention is carried out.

In this specification, in order to simplify the explanation,
Although the method of the present invention is mainly described for the case of handling a liquid containing three or more components as a fluid raw material, it goes without saying that the method of the present invention can be applied to a gas containing three or more components.

[0035]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Embodiments of the present invention will be described below with reference to the drawings. However, it is obvious that the present invention is not limited to the following embodiments without departing from the gist thereof.

FIG. 1 is a diagram showing an outline of an example of the configuration of a simulated moving bed type chromatographic separation apparatus that can be used in carrying out the method of the present invention. In FIG. 1, 1 to 10
Is a unit packed tower (unit packed bed), 1A to 10A are extraction valves for A fraction, 5B is extraction valve for B fraction, 1C to 10C are extraction valves for C fraction, 1D to 10D are desorbing agents such as eluent. A supply valve, f is a fluid material supply valve, A is a fraction fluid of component A, B is a fraction fluid of component B, B is a fraction fluid of component C, and C is a fraction of component C. Fluid, D is a desorbing agent such as an eluent, F is a fluid raw material, 12 is an A fraction extraction pipe, 13 is a B fraction extraction pipe, 14 is a C fraction extraction pipe, 15
Is a fluid material supply pump, 16 is a desorbent supply pump, 19
Denotes a circulation pump, 20 and 21 denote connecting pipes, 30 denotes a fluid source supply pipe, and 31 denotes a desorbent supply pipe.

Each end of the unit packed towers 1 to 10 is
Endlessly connected to the top of the next unit packed tower by connecting pipes 20 and 21, and connected to the connecting pipe on the downstream side of each unit packed tower with A fraction extraction valves 1A to 10A and C fraction extraction valves 1C to 10C. , The B fraction extraction valve 5B is connected to a connection pipe on the downstream side of the unit packed tower 5, and a desorbent supply pipe for the desorbent supplied by the desorbent supply pump 16 to the connection pipe on the upstream side of each unit packed tower. Desorbent supply valve 1 branched from 31
A fluid source supply valve f for a fluid source supplied by a fluid source supply pump 15 by connecting branch pipes with D-10D;
A fluid pump supply pipe 30 is connected to a connection pipe upstream of the unit packed tower 6, and a circulation pump 19 is connected in the middle of a pipe 21 from the end of the unit packed tower 10 to the top of the unit packed tower 1. The fraction extraction valve 5B is connected to the B fraction extraction pipe 13, each of the A fraction extraction valves 1A to 10A is connected to the A fraction extraction pipe 12, and each of the C fraction extraction valves 1C to 10C.
C is connected to a C fraction extraction pipe 14, and a shutoff valve Z is provided in a connection pipe between the unit packed tower 5 and the unit packed tower 6 to constitute a simulated moving bed type chromatograph.

In the example of FIG. 1, the B fraction extraction valve 5B is connected to the connection pipe 20 downstream of the unit packed tower 5 without passing through the unit packed tower upstream of the shutoff valve Z, and the B fraction extraction pipe 13 However, the B fraction extraction valve is connected to the connection pipe 20 on the downstream side of the unit packed tower 4 via the 1 unit packed tower 5 upstream of the shutoff valve Z, and the B fraction extracted pipe 1
3 may be connected. In the latter case, `` between at least the position at which the fluid material is supplied to the filler layer and the position at which the affinity for the filler is extracted from the filler layer with an intermediate component for the filler '' is
Unit packed towers 6, 7, 8, 9, 1 excluding the unit packed tower 5
The range is 0, 1, 2, 3, and 4.

The circulation pump 19 is installed in the middle of the pipe 21 so that the flow rate can be controlled to a set value by a control device (not shown) according to a flow rate sequence program. The circulation pump 19 may be installed anywhere between adjacent unit packed towers, and may be provided as many as necessary. The opening and closing of each supply valve and each extraction valve are controlled by a control device (not shown) according to a predetermined valve opening and closing sequence program. In FIG. 1, the number of unit packed towers is ten, but the number is not limited thereto.

The opening and closing of the shut-off valve Z provided in the connection pipe between the unit packed towers 5 and 6 is controlled by a control device (not shown). The number of such shutoff valves is not limited to one, and the number may be two or more, and may be provided at different positions in the circulation flow path according to the purpose.

Next, at least three components (A component, B component,
An example in which the fluid raw material containing (C component) is separated into three fractions enriched in each component in two steps will be described. In this case, it is assumed that the strength of the affinity for the filler is in the order of C component> B component> A component.

The first step (in Examples and Comparative Examples, the first step
In the state where the shut-off valve Z is closed and the fluid material supply valve f is opened, the top of the unit packed column 6 in which the sorption zone enriched in the fraction A is formed. While supplying the fluid raw material F through the fluid raw material supply valve f from the end of the unit packed tower 8 downstream of the fluid raw material supply position with the A fraction extraction valve 8A open, While the desorbent supply valve 1D is opened, the desorbent is introduced from the top of the unit packed tower 1 upstream of the unit packed tower 5 in which the sorption zone enriched with the B component is formed. While supplying D,
With the B fraction extraction valve 5B open, the B fraction is extracted from the end of the unit packed column 5.

Since the A fraction is extracted in the following second step (corresponding to “second to tenth steps” in Examples and Comparative Examples), the first component may be removed depending on the affinity of the A component for the filler. In the process, it is possible to adopt a mode in which the process is performed without extracting the A fraction. Further, in the first step, it is possible to adopt a mode of extracting the C fraction and extracting the A fraction and the C fraction as necessary. Also, if the affinity of the strength to filler intermediate B component is made and a B ₁ component and B _2-component (Affinity: B ₁ component <B ₂ component), B
There is also a fraction withdrawal valve 5B open the state successively withdrawing ₂ fractions B enriched the enriched B ₁ fraction and B ₂ components B ₁ component from the tower end of the packing bed unit 5 in a manner, this In aspects,
Actually, four components are separated. Of course, withdrawn fraction of the B component as a fraction, only this fraction, for example, B ₁ component in substantially the same process or general 2-component separation simulated moving bed chromatographic separation process and the second step described below: It may take the enriched B ₁ fraction and B ₂ embodiment be divided into enriched B ₂ fractions of the components.

The second step ("Example 2" and "Comparative Example 2
10 stage), the supply of the fluid raw material is stopped by closing the fluid raw material supply valve f, and the shutoff valve Z is opened to circulate the fluid in the system in which the unit packed towers are connected endlessly in series. The desorbent is supplied into the reactor, and fractions of the respective residual components (fraction A and fraction C) are collected from the end of the unit packed column in which the sorption zone enriched with the components remaining in the first step is formed. ) Is extracted, and the supply position of the desorbent and the extraction position of each fraction are shifted to the unit packed tower on the downstream side of the system in accordance with the movement of the sorption zone. Specific 1 of such operation
As an example, it is possible to understand how to perform the above-described transition operation by referring to the “valve that opens” in the second to tenth stages of the first embodiment described below. In industrial-scale equipment operation,
Usually, the first step and the second step are repeated as one cycle.

In the first step, the distribution of the sorption zone of each component extracted in the next cycle while supplying the fluid raw material is formed, and the fraction of the component in which the sorption zone is already formed, This is a step of extracting a component fraction (B fraction) whose affinity to the filler is intermediate, and can extrude a large amount of the B fraction in a short time. At this time, it is preferable that the in-system fluid does not flow from the upstream to the fluid source supply position. Therefore, the shutoff valve Z is provided as a means for mechanically guaranteeing the interruption of the fluid flow. However, even if a shutoff valve is not provided, the fluid flow can be shut off operatively by controlling the supply amount of the fluid raw material and the extraction amount of the B fraction.

In the second step, while circulating the fluid in the system without supplying the fluid raw material, an operation according to a general simulated moving bed type chromatographic separation method is carried out to remove components other than the B component. The enriched fraction is extracted out of the system, and each component of the fluid raw material newly supplied to the system in the first step is converted from a component (A component) having a low affinity to a filler (sorbent) to a component having a strong affinity for a filler (sorbent). (C component) is a step for forming a sorption zone divided sequentially. Therefore, the second step is similar to a general simulated moving bed type chromatographic separation method of two-component separation except that no fluid raw material is supplied.

In the general simulated moving bed type chromatographic separation method of two-component separation, the unit packed towers connected endlessly as described above are placed in the first direction toward the downstream side as viewed from the desorbent supply position.
Section, section 2, section 3, section 4 and think,
A desorbent such as an eluent is supplied to the circulating flow at the inlet of the unit packed tower located at the front row of the first section through a supply valve, and the outlet of the unit packed tower located at the last row of the first section is provided. A C fraction fluid having a high content of sorbed components is withdrawn from the circulating flow through a withdrawal valve, and a valve is provided for supplying a fluid raw material to the circulating flow at the inlet of the unit packed tower located at the front row of the third section. And the A fraction fluid containing less sorbed components is extracted from the circulating flow at the outlet of the unit packed tower located in the last row of the third section, and the supply positions of these desorbents and the C fraction fluid The extraction position, the supply position of the fluid raw material, and the extraction position of the A fraction fluid are operated so that the components in the fluid raw material are moved down to the downstream side as the sorption region shifts to the sorbent. In the second step, each of the raw materials is newly supplied without supplying the fluid raw material. Min is characteristically to prevent flow into the system.

The method of performing the second step, that is, the operation of the simulated moving bed system in which two fractions are extracted while supplying the desorbent, is not particularly limited, except that the supply of the fluid raw material is not performed. In this case, the supply of the undiluted solution should not be performed in a conventionally known example, for example, in the method described in JP-A-62-91205, particularly, page 2, upper right column, second line to lower left column, last line and FIG. A case in which the process is carried out can be given as an example. Specifically, while circulating the fluid in the system by a pump or the like, the desorbent is supplied from the upstream tower top of the zone where the high affinity component is enriched, and the high affinity component is enriched. The fraction enriched with the component is withdrawn from each downstream column of the zone in which the component is enriched and the zone in which the component having a low affinity is enriched, and these are successively recirculated in accordance with the movement of each zone. The operation of shifting to the downstream is performed by performing a plurality of components other than the intermediate component having an affinity for the filler (sorbent).

The operation of repeating the first step and the second step described above has been described in connection with the state in which the apparatus is continuously operated. However, in order to start up the apparatus, the fluid must be supplied prior to the first step. Filling materials (sorbent) by supplying raw materials into the system
A pre-process in which only an operation for forming a sorption zone that is sequentially separated from a component having a low affinity to a component having a high affinity may be performed.

Basically, the first step and the second step are repeated as one cycle, but it goes without saying that the present invention can be carried out in various modified forms.

For example, in the first step, it is possible to supply only the fluid raw material into the system and not supply the desorbent. However, by simultaneously supplying the fluid raw material and the desorbing agent as described above, it is possible to adjust the supply amount of the fluid raw material and the extraction amount of the B fraction (adjustment of mass balance). Further, by supplying the desorbing agent, the flow velocity of the fluid downstream thereof is increased, so that the moving speed of the predetermined component in the sorption zone can be arbitrarily selected.

[0052]

EXAMPLES Hereinafter, the method of the present invention will be described in detail with reference to examples, while comparing with comparative examples, but it goes without saying that the method of the present invention is not limited to these examples. In the following Examples and Comparative Examples, the composition per solid content is represented by the area percentage of high performance liquid chromatography using a sodium ion exchange column and a differential refractometer, and "1 cycle"time"
Represents the time required to complete all the stages from the first stage to the tenth stage. Generally speaking, each step can be performed continuously over a plurality of cycles, if necessary, without ending in one cycle.

Example 1 A liquid obtained by decomposing beet molasses with a sucrose degrading enzyme invertase and desalting by an ion exclusion method (solid content: 60% by weight, composition per solid content: polysaccharides of two or more saccharides and other unknown components) 11.4%, glucose 39.7%, fructose 40.6%, betaine 8.3%) as a stock solution to obtain a mixed sugar solution of glucose and fructose. Separation was carried out by a simulated moving bed type chromatographic separation apparatus in which three or more components of FIG. 1 were filled with a cation exchange resin of 49% of potassium form and 21% of sodium form as a filler. However, as shown below, potassium form 49
% And 21% of the sodium form were present as mixed ion forms within each grain of the cation exchange resin.

As a filler, Amberlite CG-6000 (a gel-type strongly acidic cation exchange resin for chromatographic separation) manufactured by Rohm and Haas Company was used. The cation exchange resin as the second filler in the unit packed towers 1, 2, 7 is in a calcium form, and the remaining unit packed towers 3, 4, 5, 6,
The cation exchange resin as the first filler in 8, 9, and 10 was a mixed ion form of 70% potassium form and 30% sodium form. The cation exchange resin in the mixed ion form of the potassium form and the sodium form forms the ionic composition of the raw material liquid (softened liquid) when the saccharide is separated from the softened liquid of the aqueous saccharide solution derived from plants (sugar beet). This was obtained as a mixed ion type cation exchange resin of 70% potassium form and 30% sodium form in equilibrium. The calcium form of the cation exchange resin in the unit packed towers 1, 2, 7 is
An aqueous calcium chloride solution having a concentration of 1 N is flowed through the mixed ion type cation exchange resin into the calcium form by flowing 44 L per unit packed column. The filling amount of the filler was 147 L in total in the ten unit packed towers.

The degree of separation of disaccharides and glucose is 0.3 with a mixed ion type cation exchange resin (70% potassium form: 30% sodium form) of monovalent ions of the first filler.
0, with a calcium-type cation exchange resin as the second filler.
27. As can be seen from the above-mentioned degree of separation of the first filler, disaccharides and monosaccharides such as glucose are originally well separated by using a monovalent ion type strongly acidic cation exchange resin. If so, the first filler and the second filler may not be mixed. In addition, the separation of fructose (a component having a higher affinity with monosaccharides which flows out later than glucose) and betaine is 0.03 for the monovalent ion mixed cation exchange resin of the first filler, and calcium for the second filler. It was 0.76 for the cation exchange resin.
Therefore, in the present example, the separation of monosaccharides such as fructose and betaine was not good in the first filler, so that it was improved and monosaccharides, disaccharides and others, and betaine were considered as three components. Is intended to be separated with as little elution water as possible and in a well-balanced manner. The degree of separation was as follows: temperature 60 ° C., packed bed height 1 m, linear flow rate 5
It was measured in m / Hr.

Other operating conditions were as follows. Unit packed tower: inner diameter 108 mm, bed height 1600 mm, unit packed tower number 10 Operating temperature: 60 ° C. One cycle time: 2.25 Hr In the first stage (first step), required time in the first stage: 0.45 Hr Undiluted solution supply Amount: 16.54 L / Hr (average 0.0 per filler and per cycle time)
223 L / L-filler / Hr) Eluent water supply: 57.15 L / Hr A fraction withdrawal amount: 9.91 L / Hr B fraction withdrawal amount: 64.50 L / Hr 2nd to 10th stages (No. In step 2), the linear flow velocity in the unit packed tower between the A fraction liquid discharge port and the C fraction liquid discharge port: 5.00 m / Hr Eluate water supply amount: 46.31 L / Hr A fraction liquid discharge amount: 16 .54 L / Hr C fraction withdrawal amount: 29.77 L / Hr Eluent water / stock solution (volume ratio): 9.7

The valves opened at each stage were as follows. 1st stage f, 1D, 8A, 5B (supply of undiluted solution, supply of elution water, extraction of A fraction, extraction of B fraction) Second stage 2D, 9A, 3C, Z (supply of eluent water, extraction of A fraction, C extraction 3rd stage 3D, 10A, 4C, Z (eluent water supply, A fraction extraction, C fraction extraction) 4th stage 4D, 1A, 5C, Z (eluent water supply, A fraction extraction, C image) 5th stage 5D, 2A, 6C, Z (supply of elution water, extraction of A fraction, extraction of C fraction) 6th stage 6D, 3A, 7C, Z (supply of eluent water, extraction of A fraction, C image) 7th stage 7D, 4A, 8C, Z (eluent water supply, A fraction extraction, C fraction extraction) 8th stage 8D, 5A, 9C, Z (eluent water supply, A fraction extraction, C image) 9D, 6A, 10C, Z (eluent water supply, A Min withdrawn, withdrawn fraction C) 10 stage 10D, 7A, 1C, Z (eluent water feed, withdrawal A fraction withdrawal fraction C)

In the first stage (first step), the stock solution F is supplied to the unit packed column 6 via the stock solution supply valve f located downstream of the closed shut-off valve Z, and at the same time, the eluate D is supplied to the eluate. Valve 1
By supplying the liquid via D, the B fraction liquid is extracted via the extraction valve 5B on the upstream side of the shutoff valve Z, and the A fraction liquid is extracted via the extraction valve 8A. On the other hand, in the second to tenth stages (second step), the shut-off valve Z is opened, the supply of the undiluted solution is stopped, and the supply position of the eluent water and the extraction positions of the fractions A and C are sequentially moved to the downstream side. While the eluate is being supplied, the A and C fractions are extracted.

As a result of the operation, fractions A, B and C having the following solid contents and compositions per solid were obtained. A fraction liquid B fraction liquid C fraction liquid Concentration 31 g / L 160 g / L 17 g / L Disaccharide, others 98.8% 0.6% 0.1% Glucose 0.5% 49.3% 0.1 % Fructose 0.0% 49.5% 10.7% betaine 0.7% 0.6% 89.1%

The glucose recovery rate of the B fraction was 9%.
9.8%, the fructose recovery was 97.6%, and the betaine recovery in the C fraction was 93.8%.

Comparative Example 1 The same stock solution as in Example 1 was separated in the same apparatus and at the same temperature while using the mixed ion type cation exchange resin of the potassium and sodium forms as the packing material in all unit packed columns. The operating conditions are
The following was made according to the mixed ionic composition of the cation exchange resin. In particular, since the flow-out of betaine was rapid, it was wasted to use the same amount of eluent water as in Example 1, so the amount of eluate used was reduced.

As a filler, Amberlite CG-6000 (a gel-type strongly acidic cation exchange resin for chromatographic separation) manufactured by Rohm and Haas Company was used. The cation exchange resin was converted into a mixed ion form of 70% potassium form and 30% sodium form in all unit packed columns. Incidentally, the mixed ion type cation exchange resin of the potassium form and the sodium form,
When chromatographic separation of saccharides was performed from a softened solution of an aqueous saccharide solution derived from a plant (sugar beet), it was obtained as a mixed ion-type cation exchange resin having an ionic form composition in equilibrium with the ionic form composition of the raw material liquid (softened liquid). It is something that is used as it is. The packing amount of the filler is 1 in the total amount in 10 unit packed towers.
It was 47L.

The other operating conditions were as follows. Unit packed tower: inner diameter 108 mm, bed height 1600 mm, unit packed tower number 10 Operating temperature: 60 ° C. One cycle time: 2.24 Hr In the first stage (first step), required time in the first stage: 0.32 Hr Stock solution supply Amount: 22.97 / Hr (average 0.0223 L / L-filler / filler / cycle time)
Hr) Eluent water supply: 55.13 L / Hr A fraction withdrawal amount: 9.19 L / Hr B fraction withdrawal amount: 68.91 L / Hr In the 2nd to 10th stages (second step), the A fraction Linear flow velocity in the unit packed tower between the liquid separation outlet and the C fraction liquid outlet: 5.00 m / Hr Eluent water supply: 24.66 L / Hr A fraction withdrawal: 17.61 L / Hr C fraction Liquid withdrawal amount: 7.05 L / Hr Eluent water / stock solution (volume ratio): 5.8

The valves to be opened at each stage, the supplied liquid and the extracted liquid were the same as in Example 1.

As a result of the operation, fraction A, fraction B and fraction C having the following solid contents and compositions per solid were obtained. Fraction A Fraction B Fraction C Fraction Concentration 31 g / L 225 g / L 16 g / L Disaccharide, other 98.8% 0.5% 0.3% Glucose 1.0% 45.4% 0.2 % Fructose 0.1% 45.4% 60.4% Betaine 0.1% 8.7% 39.1%

The glucose recovery rate of the B fraction was 9%.
The fructose recovery was 9.7%, and the betaine recovery in the C fraction was 9.3%.

Comparative Example 2 The same stock solution as in Example 1 was separated at the same apparatus and at the same temperature, except that the total filler in all unit packed columns was changed to a calcium-type cation exchange resin. The operating conditions were as follows according to the ion form of the cation exchange resin. In particular, since the flow-out of betaine was slow, if only the same amount of eluent water as in Example 1 was used, the amount of eluted water was increased because betaine was mixed into fraction A due to insufficient eluent water.

As a filler, Amberlite CG-6000 (a gel type strongly acidic cation exchange resin for chromatographic separation) manufactured by Rohm and Haas Company was used. All cation exchange resins were in calcium form in all unit packed columns. This calcium-type cation exchange resin is a mixed ion-type cation-exchange resin having an ion-type composition that is in equilibrium with the ion-type composition of the raw material liquid when a saccharide is separated from a softened solution of an aqueous saccharide solution derived from a plant (sugar beet). An aqueous calcium chloride solution having a concentration of 1 N is flowed through the cation exchange resin obtained as the exchange resin at a rate of 44 L per unit packed column to obtain a calcium form. The filling amount of the filler was 147 L in total in the ten unit packed towers.

Other operating conditions were as follows. Unit packed tower: inner diameter 108 mm, bed height 1600 mm, unit packed tower number 10 Operating temperature: 60 ° C. One cycle time: 2.36 Hr In the first stage (first step), required time in the first stage: 0.56 Hr Stock solution supply Amount: 13.78 L / Hr (1 per filler and
0.0223 L / L-filler / Hr average per cycle time) Eluent water supply: 51.45 L / Hr A fraction withdrawal: 10.11 L / Hr B fraction withdrawal: 55.12 L / Hr In the 2nd to 10th stages (second step), the linear flow velocity in the unit packed tower between the A fraction liquid discharge port and the C fraction liquid discharge port: 5.00 m / Hr Eluate water supply amount: 89.30 L / Hr A Fraction withdrawal amount: 18.19 L / Hr C Fraction withdrawal amount: 71.11 L / Hr Eluent / stock solution (volume ratio): 15.3

The valves to be opened at each stage, the supplied liquid and the extracted liquid were the same as in Example 1.

As a result of the operation, fraction A, fraction B and fraction C having the following solid contents and compositions per solid were obtained. A fraction liquid B fraction liquid C fraction liquid Concentration 27 g / L 157 g / L 7 g / L Disaccharide, others 98.0% 1.1% 0.0% Glucose 0.8% 48.7% 0.1 % Fructose 0.0% 49.9% 1.3% Betaine 1.2% 0.3% 98.6%

The glucose recovery rate of the B fraction was 9%.
9.8%, the recovery of fructose was 99.7%, and the recovery of betaine in the C fraction was 95.7%.

When comparing Example 1 with Comparative Example 1, Example 1
In this example, the amount of eluted water used was increased by 69% compared to Comparative Example 1, but the betaine concentration in the B fraction was 8.1 compared to Comparative Example 1.
%, And the total purity of glucose and fructose was 8.0% higher than that of Comparative Example 1. The betaine purity of the fraction C was 39.1% in Comparative Example 1, whereas Example 1 was low. In this case, high purity betaine could be recovered as high as 89.1%. That is, 30 of the ion form of the cation exchange resin
%, The amount of eluted water used increased, but monosaccharides (glucose + fructose)
Separation of betaine and betaine was greatly improved, and the overall degree of separation was adjusted to a necessary and sufficient level, so that the target mixed saccharide solution of glucose and fructose could be recovered with high purity and high recovery.

When comparing Example 1 with Comparative Example 2, Example 1
Thus, the betaine purity of the C fraction was higher than that of Comparative Example 2 by 9.5.
%, And the betaine recovery was reduced by 1.9%. However, considering that a crystallization step is required to obtain betaine, these differences are not a serious problem. In Example 1, the amount of eluate used was reduced by 36% compared to Comparative Example 2, and the total purity of glucose and fructose in the B fraction was increased by 0.2%. That is, only 30% of the cation exchange resin was changed from the ionic form to the calcium form, so that the degree of separation between monosaccharides (glucose + fructose) and betaine was sufficiently and sufficiently adjusted. Without any difficulty, the target mixed sugar solution of glucose and fructose could be recovered with high purity.

[0075]

According to the present invention, in a chromatographic separation method for separating a fluid raw material containing three or more components into three or more fractions each of which is enriched with each component, at least the position where the fluid raw material is supplied to the filler layer By using two or more kinds of fillers having different resolutions between the positions at which the components having an affinity for the filler from the middle are extracted from the filler layer, the overall resolution can be adjusted. This has the effect of reducing the amount used, increasing the purity of the target substance, and increasing the recovery rate of the target substance. In each of the conventional chromatographic separation methods described above, in order to reduce the amount of desorbent (eluent) used, the eluent may be, for example, a mixture of ethanol and water with an appropriate composition,
In contrast, this method has a problem that it cannot be applied to a case where only an eluent of a single solvent such as water can be used as a desorbent, whereas the method of the present invention uses a single pure substance desorbent, There is an advantage that the amount used can be reduced.

In addition, the method of the present invention is designed to appropriately separate both components that are excessively separated from each other and components that are not separated particularly when three-component separation is performed using a three-component chromatographic separation apparatus. There is an effect that it can be adjusted.

[Brief description of the drawings]

FIG. 1 is a diagram showing an outline of an example of a configuration of a simulated moving bed apparatus type chromatographic separation apparatus capable of carrying out the method of the present invention.

[Explanation of symbols]

1 to 10: Unit packed tower 1A to 10A: Extraction valve for A fraction 5B: Extraction valve for B fraction Z: Shutoff valve 1C to 10C: Extraction valve for C fraction 1D to 10D: Desorbent supply valve f: Fluid Material supply valve A: A fraction fluid (fluid with high content of components with low affinity) B: B fraction fluid (fluid with high content of components with intermediate affinity) C: C fraction fluid (fluid with high affinity) D: Desorbent (eg, elution water) F: Fluid raw material (eg, sugar solution) 12: A fraction extraction pipe 13: B fraction extraction pipe 14: C fraction Extraction pipe 15: Fluid raw material supply pump 16: Desorbent supply pump 19: Circulation pump 20, 21: Piping 30: Fluid raw material supply pipe 31: Desorbent supply pipe

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[Procedure amendment]

[Submission date] June 7, 1999

[Procedure amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0042

[Correction method] Change

[Correction contents]

The first step (in Examples and Comparative Examples, the first step
In corresponding to stage "), a shutoff valve Z a closed and a starting fluid material feed valve f an open and a state, the top of the packing bed units 6 A Ingredient is formed of enriched sorption band While supplying the fluid raw material F through the fluid raw material supply valve f from the end of the unit packed tower 8 downstream of the fluid raw material supply position with the A fraction extraction valve 8A open, While the desorbent supply valve 1D is opened, the desorbent is introduced from the top of the unit packed tower 1 upstream of the unit packed tower 5 in which the sorption zone enriched with the B component is formed. While supplying D,
With the B fraction extraction valve 5B open, the B fraction is extracted from the end of the unit packed column 5.

[Procedure amendment 2]

[Document name to be amended] Statement

[Correction target item name] 0063

[Correction method] Change

[Correction contents]

The other operating conditions were as follows. Unit packed tower: inner diameter 108 mm, bed height 1600 mm, unit packed tower number 10 Operating temperature: 60 ° C. One cycle time: 2.24 Hr In the first stage (first step), required time in the first stage: 0.32 Hr Stock solution supply Amount: 22.9 5 L / Hr (1 per filler and 1
0.0223 L / L-filler / Hr average per cycle time) Eluent water supply: 55.13 L / Hr A fraction withdrawal: 9.19 L / Hr B fraction withdrawal: 68.91 L / Hr In the 2nd to 10th stages (second step), the linear flow rate in the unit packed tower between the A fraction liquid discharge port and the C fraction liquid discharge port: 5.00 m / Hr Eluate water supply: 24.66 L / Hr A Fraction withdrawal amount: 17.61 L / Hr C Fraction withdrawal amount: 7.05 L / Hr Eluent / stock solution (volume ratio): 5.8

[Procedure amendment 3]

[Document name to be amended] Statement

[Correction target item name] Fig. 1

[Correction method] Change

[Correction contents]

FIG. 1 is a diagram showing an outline of an example of a configuration of a simulated moving bed type chromatographic separation apparatus capable of carrying out the method of the present invention.

Continuing from the front page (72) Inventor Kohei Sato 1-4-9, Kawagishi, Toda City, Saitama Prefecture Inside Organo Research Institute (72) Inventor Koji Tanigawa 1-4-9, Kawagishi, Toda City, Saitama Prefecture Organo Stock Inside the company research institute

Claims (4)

[Claims] 1. A fluid material containing three or more components is passed through a filler layer, and three or more components having different affinities ranging from components having high affinity to fillers contained in the fluid material and components having low affinity are passed through the filler layer. A method for chromatographic separation into at least three fractions, wherein the affinity for a filler is at least between a position at which a fluid raw material is supplied to a filler layer and a position at which an affinity component is extracted from the filler layer. The filler that is in contact with the fluid containing the components is two or more types of fillers having different degrees of separation for the respective components, and the filler between the two positions composed of the two or more types of fillers is at least filled. A first filler having a high degree of separation between a component having an intermediate affinity for a filler and a component having a low affinity for a filler, a component having a high affinity for a filler, and a component having an intermediate affinity for a filler Chromatographic separation method of, characterized in that the mixed state in combination with the separation of a large second filler between to adjust the separation of each component. 2. The filler layer is formed by connecting a plurality of unit filler layers, and at least one of the two or more fillers is independently filled in at least one unit filler layer. The method for separating chromatographs according to claim 1, wherein 3. The method according to claim 2, wherein the fluid raw material is a raw material liquid.
The separation operation is performed under the condition that at least one of the at least one kind of filler is an ion exchanger and that the ionic composition of the raw material liquid and the separation treatment liquid does not substantially change. 3. The chromatographic separation method according to 1 or 2. 4. The method according to claim 1, wherein one of the two or more fillers is a monovalent ion form of a strongly acidic cation exchange resin, and the other is a divalent ion form of a strongly acidic cation exchange resin. The chromatographic separation method according to any one of claims 1 to 3.