JP2968107B2 - Chromatographic separation method - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a simulated moving bed in which a number of packed columns packed with an adsorbent having a selective adsorption capacity for three or more components contained in a stock solution are connected in series and endlessly. The present invention relates to a separation method using a chromatographic separation apparatus, for example, a method of separating maltose, glucose and fructose, a method of separating maltotriose, maltose and glucose, and the like.

[0002]

2. Description of the Related Art Conventionally, a chromatographic separation method in which a liquid containing two components is passed through a packed tower filled with an adsorbent to separate and recover fractions enriched in these components is a fixed bed type, a simulated mobile method. It is also known as a bed type or a fluidized bed type.
For the purpose of separating the above components, a simulated moving bed type chromatographic separation method has attracted attention, and some proposals have already been made.

[0003] As a method for separating multiple components using such a simulated moving bed type chromatographic separation apparatus, there are many methods in which an adsorbent packed with an adsorbent having a difference in adsorption capacity for three or more components contained in a raw material fluid is used. Is connected in an endless series with piping together with one or several circulating pumps, and a raw material fluid is flowed through the packed tower group so that each component is enriched from upstream to downstream. It is typically known that a first section, a second section, a third section, and a fourth section are formed and the following operations a and b are repeated.

A: The shut-off valve between the second section and the third section is closed, and the desorbent is discharged from the inlet of the packed column in the first row of the first section.
The raw material is supplied from the inlet of the packed tower located in the front row of the third section, and the component B having the strongest and weakest affinity for the adsorbent is obtained from the outlet of the packed tower located in the last row of the second section. First step of discharging the separated fraction b: Opening the shut-off valve and supplying the desorbent from the inlet of the packed column in the front row of the first section while circulating the fluid in the packed bed, The fraction enriched in the component A having a low affinity for the adsorbent from the packed column in the last column is enriched with the component C having a high affinity for the adsorbent from the outlet of the packed column located in the last column of the first compartment. A second step of causing the fractions to flow out, and sequentially moving the supply position of the desorbent and the discharge position of each fraction to the downstream side by a rotary valve or a valve attached to each column.

[0005]

However, the flow rate control of the conventional multi-component separation simulated moving bed type chromatographic separation apparatus described above is complicated, and high-performance and expensive flow control equipment is required. In particular, there has been a demand for an inexpensive multi-component separation simulated moving bed type chromatographic separation method which is compact, can be used for a variety of purposes, can be easily controlled, and is inexpensive.

From the above viewpoints, the present inventors have conducted various studies and have developed the present invention for the purpose of providing an inexpensive multi-component separation simulated moving bed type chromatographic separation method which is easy to control. .

[0007]

The present inventor has completed the method of the present invention described in each of the above claims in order to achieve the above objects.

A feature of the method of the present invention is that, typically, an endless packed tower system in which a plurality of packed towers filled with an adsorbent are connected in series with pipes each having a shutoff valve, The three compartments formed when a raw material fluid containing three or more components having different affinities to the system are passed through the system (components having a high affinity for the adsorbent (hereinafter, referred to as “component C”). A first section composed of a plurality of packed tower groups, one or more packed tower groups enriched in a component having an intermediate affinity for an adsorbent (hereinafter referred to as “component B”), and a component having an intermediate affinity for the adsorbent B and a second section composed of one or more packed tower groups in which the component C having a high affinity is mixed, a component having a low affinity for the adsorbent (hereinafter, “component A”)
Is divided into a third section comprising the remaining packed tower group including one or a plurality of packed tower groups enriched).
, Or the process is alternately repeated in the order of, or in the order of,.

In a state where the shutoff valve between the second section and the third section is closed to shut off the circulation of the fluid in the entire system, the feed fluid is supplied from the inlet of the packed tower located immediately downstream of the shutoff valve. While performing the operation of flowing out the fraction enriched in the component B from the outlet of any of the packed towers in the second compartment,
Step of shifting the distribution of the first section to the third section to the downstream side by at least one packed tower. Following the above-described step, with the shutoff valve between the shifted third section and the first section closed, Draining the fraction enriched with component C from the outlet of the most downstream packed tower of the first compartment while supplying the desorbent fluid from the inlet of the packed tower located at the most upstream of one compartment; Discharging the fraction enriched in the component A from the outlet of the packed tower located at the most downstream position of the third section, and furthermore, the distribution of the first section to the third section is such that the downstream side of the fluid has one charge. Synchronizing with the transfer by the column, the supply position of the desorbent fluid, the extraction position of each fraction,
And the step of repeating the same operation by lowering the position of the shut-off valve to be shut off by one packed tower for a predetermined number of times. Following the above-described steps, with the shut-off valve between the third section and the first section closed, Distributing the desorbent fluid from the inlet of the packed tower located at the uppermost stream of the first section, and discharging the fraction enriched with the component C from the outlet of the packed tower at the lowermost stream of the first section. An operation of discharging the fraction enriched with the component A from the outlet of the packed tower located at the most downstream position of the third section; and an operation of discharging the component B from the outlet of the packed tower located at the most downstream position of the second section. Discharging the enriched fraction, and, if necessary, synchronizing the distribution of the first section to the third section to the downstream side of the fluid by one packed column, and the desorbent fluid The supply position, the extraction position of each fraction, and the position of the shut-off valve for shutting off Repeating the same operation by moving down only a predetermined number of times.

In the above description, the first section comprising one or a plurality of packed tower groups enriched with the component C does not strictly require that only the component C is enriched. For example, when the component to be separated and recovered is mainly B and the component C is sufficient for the purpose of removal only, the component B is mixed in the most downstream packed tower of the first section. The packed tower group that forms the first compartment can be set according to the purpose to be implemented, the type of the components contained in the raw material fluid, and the like so that there is no problem. The same applies to the second section and the third section.

In the above-mentioned process, the operation of supplying the desorbent fluid from the inlet of the most upstream packed tower in the first section and the step of supplying the component C-enriched fraction from the outlet of the most downstream packed tower in the first section are performed. And / or the operation of discharging the fraction enriched in component A from the outlet of the packed tower at the most downstream side of the third section may be performed simultaneously or sequentially.

Further, the shut-off valve closed in the above step is not limited to the shut-off valve between these sections as long as the flow of the fluid from the second section to the third section can be prevented. Therefore, in this case, while supplying the raw material fluid from the inlet of any of the packed towers located relatively upstream in the third section located downstream of the closed shut-off valve, the feed fluid is located upstream of the closed shut-off valve. The component B-enriched fraction can be discharged from the outlet of any of the packed towers located relatively downstream in the second section. Here, the fact that the packed tower for supplying the raw material fluid is relatively upstream of the third section means that it does not have to be the most upstream packed tower in the third section depending on the distribution state and nature of the component A. In general, the most upstream packed tower or the next downstream packed tower is selected, but the present invention is not limited to this depending on the number of packed towers and the like. Similarly, the fact that the packed column from which the component B is discharged is located relatively downstream in the second section generally means that the packed column is the most downstream packed column in the second section or the packed column immediately upstream thereof. A tower is selected, but is not limited to this depending on the number of packed towers installed.

In the above step, before and / or after this step, the desorbent fluid is supplied from the inlet of the packed tower located at the most upstream of the first section, while the desorbent fluid is supplied to the most downstream of the first section. Discharging the fraction enriched in the component C from the outlet of the packed tower, and supplying the desorbent fluid from the inlet of the packed tower located at the uppermost stream of the first section, Discharging the fraction enriched in component A from the outlet of the packed tower located at the same time, sequentially, or simultaneously with these operations, and furthermore, at least one of these operations Either one may be performed sequentially.

Further, in the step to be repeated, or in this step and the step to be performed thereafter, prior to the operation for each repetition, the shut-off valves in the system are all opened. Distributing the desorbent fluid from the inlet of the packed tower located at the most upstream position of the first section, and discharging the fraction enriched with component C from the outlet of the packed tower located at the most downstream side of the first section. It is also preferable to carry out.

[0015]

According to the method of the present invention, the number of sections is one compared to the conventional method in which the packed tower group system is divided into four sections.
Since the number is 3 which is small, there is an effect that it is not necessary to control the flow rate for flowing out the fraction of the component having a low affinity for the adsorbent.

The method further comprises the step of closing the shut-off valves of the third section and the first section, and supplying the fluid from the packed tower located at the last row of the third section to the packed tower located at the front row of the first section. The addition has the effect of reducing the amount of the desorbing agent used.

[0017] Furthermore, in a method in which a step of flowing out only a component having a high affinity for the adsorbent and / or a step of flowing out only a component having a low affinity for the adsorbent is added, the separation performance can be improved. effective.

[0018]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described in detail below with reference to embodiments, but it is needless to say that the present invention is not limited to these embodiments.

Example 1 (Malt triose and maltoux)
Graphics and separation of glucose) Figure 1 is an explanatory diagram showing a flow of a device used in this embodiment.

A packed tower T having an inner diameter of 3.7 cm and a length of 50 cm
(T1 ... T8) The ends of each of the eight pipes are connected endlessly to the top of the next packed tower via a shutoff valve K (K1 ... K8) via a pipe H, and the upstream side of each shutoff valve K A outflow valve A (A1 ... A8) and B solution outflow valve B (B4, B
5, B6), the liquid C outflow valve C (C1... C8) and the circulation valve M (M1... M8), and the undiluted liquid supply valve F is connected to the pipe H downstream of each shutoff valve K. (F1 ... F
8) and the eluent supply valve D (D1 ... D8),
Further, an experimental apparatus was used in which the other end of the circulation valve M was connected to the inlet of the eluent pump P11, and a check valve was provided upstream of the connection. Each packed tower was packed with a strong acidic cation exchange resin Amberlite CG-6000 Na type.

The shut-off valve is normally open, and each supply valve, each outflow valve, and the circulation valve are normally closed valves.

FIG . 2 is a flowchart showing the operation of each step of this embodiment.
FIG. 4 is an explanatory diagram showing the distribution of each component. In one step, the shut-off valve K5 is operated to shut off the flow between the packed towers 5 and 6, the stock solution supply valve F6 is opened, the stock solution is introduced from the top of the packed tower T6, and the eluate supply valve D1 is opened. Water was introduced as an eluent from the top of the packed tower T1, and the liquid B outflow valve B5 was opened to extract a liquid containing a large amount of maltose (liquid B) from the bottom of the packed tower T5 (1 in FIG . 2) .

After a predetermined time has elapsed, as two steps, the shut-off valve K1 is closed and the eluent supply valves D2, A
The liquid outflow valves A1 and C3 were opened (see FIG. 2).
2) .

The shut-off valve to shut off and the eluent supply valve to be opened, the liquid A outflow valve, and the liquid C outflow valve were sequentially moved along the liquid flow direction until the eight steps. In the first embodiment, the circulation valve M was closed in all the steps.

The above steps 1 to 8 were defined as one cycle, and 21 cycles were repeated.

The composition of the stock solution and the operating conditions are shown in Table 1 below, and the composition of each recovered fraction is shown in Table 2 below.

[0027]

[Table 1]

[0028]

[Table 2]

Example 2 In this example, the apparatus shown in FIG. 1 was used.

The shutoff valve is normally open, and each supply valve, each outflow valve, and the circulation valve are normally closed valves.

FIGS. 3 and 4 show the operation of each step of this embodiment.
It is explanatory drawing which shows a working flow and distribution of each component. In one step, the shutoff valve K5 is operated to shut off the flow between the packed towers 5 and 6, the stock solution supply valve F6 is opened, the stock solution is introduced from the top of the packed tower T6, and the solution B outflow valve B5 is opened to fill. A liquid containing a large amount of maltose (liquid B) was extracted from the bottom of the tower T5.
(1 in FIG . 3) .

After a predetermined time has elapsed, as one of two processes, the shutoff valve K1 is closed, and the circulation valve M1, the eluent supply valve D2, and the C liquid outflow valve C3 are opened (2 in FIG. 3).
-1) . After a lapse of a predetermined time, the circulation valve M1 was closed, and the liquid A outflow valve A1 was opened (2-2 in FIG . 4) .

Similarly, up to eight steps, a shutoff valve for shutting off, a circulation valve for opening and closing, and an eluent supply valve to be opened,
The liquid outflow valve and the C liquid outflow valve were sequentially moved along the liquid flow direction.

The above steps 1 to 8 were set as one cycle, and 21 cycles were repeated.

The composition of the stock solution and the operating conditions are shown in Table 3 below, and the composition of each collected fraction is shown in Table 4 below.

[0036]

[Table 3]

[0037]

[Table 4]

Assuming that one cycle of valve opening / closing, that is, from step 1 to step 8, is one cycle, the composition of the effluent after 21 cycles is as shown in Table 4, and the amount of eluent used is smaller than that in Example 1. The concentration of the fraction A increased as the amount decreased.

Example 3 In this example, the apparatus shown in FIG. 1 was used.

The shut-off valve is normally open, and each supply valve, each outflow valve, and the circulation valve are normally closed valves.

FIGS. 5 to 8 show the operation of each step in this embodiment.
It is explanatory drawing which shows a flow and distribution of each component. In one step, the shutoff valve K5 is operated to shut off the flow between the packed towers 5 and 6, the stock solution supply valve F6 is opened, the stock solution is introduced from the top of the packed tower T6, and the solution B outflow valve B5 is opened to fill. A liquid containing a large amount of maltose (liquid B) was extracted from the bottom of the tower T5.
(1 in FIG . 5) .

After a lapse of a predetermined time, as one of two processes, the shutoff valve K1 was closed, and the circulation valve M1, the eluent supply valve D2, and the C liquid outflow valve C3 were opened (from the third section). The effluent is supplied to the first section) (2-1 in FIG . 5) .

After a lapse of a predetermined time, the shut-off valve K1 and the circulation valve M1 were closed (only C was extracted) in addition to the first of the two processes as the second of the two processes (2-2 in FIG . 6) .

After a lapse of a predetermined time, the liquid A outflow valve A1 was opened (A and C) in addition to the two of the two steps as the third of the two steps.
(2-3 in FIG . 7) .

After a lapse of a predetermined time, in step 2 of step 2, the liquid C outflow valve C3 opened in step 3 of step 2 was closed, and the other valves were left as they were (only A was extracted) (FIG. 8 ) . 2-
4) .

The shutoff valve, circulation valve, eluent supply valve, liquid A outflow valve, and liquid C outflow valve, which open and close, were sequentially moved along the liquid flow direction up to eight steps.

The above steps 1 to 8 were defined as one cycle, and 20 cycles were repeated.

The composition of the stock solution and the operating conditions are shown in Table 5 below, and the composition of each collected fraction is shown in Table 6 below.

[0049]

[Table 5]

[0050]

[Table 6]

When one cycle of the opening and closing of the valve, that is, from step 1 to step 8 is defined as one cycle, the composition of the effluent after 20 cycles is as shown in Table 6, and the composition of each section is smaller than that in Examples 1 and 2. The purity of the target component was improved.

[Brief description of the drawings]

FIG. 1 is an explanatory diagram showing a schematic configuration of an apparatus used in an embodiment.

FIG. 2 is an explanatory diagram showing an operation flow and a distribution of each component according to the first embodiment.

FIG. 3 is an explanatory diagram showing an operation flow and a distribution of each component in Example 2.

[4] FIG. 4 is an explanatory view showing the distribution of the operation flows and the ingredients of Example 2.

[5] FIG. 5 is an explanatory view showing the distribution of the operation flows and the ingredients of Example 3.

[6] FIG. 6 is an explanatory diagram showing the distribution of the operation flows and the ingredients of Example 3.

[Figure 7] Figure 7 is an explanatory view showing the distribution of the operation flows and the ingredients of Example 3.

[Figure 8] Figure 8 is an explanatory view showing the distribution of the operation flows and the ingredients of Example 3.

[Explanation of symbols]

T1 to T8: packed tower, A1 to A8: liquid A outflow valve, A9:
Back pressure valve B4 to B6: B liquid outflow valve, C1 to C8: C liquid outflow valve, D1 to D8: eluent supply valve, D9: check valve, F1 to F
8: Stock solution supply valve K1 to K8: Shutoff valve, M1 to M8: Circulation valve, P11: Eluent solution supply pump P12: Stock solution supply pump, P13: C solution extraction pump, H: Packing tower connection pipe, I: B solution extraction Piping, J: circulation piping.

Continuation of front page (72) Inventor Kikuzo Kaneko 5-16, Hongo, Bunkyo-ku, Tokyo Organo Co., Ltd. (58) Field surveyed (Int. Cl. ⁶ , DB name) B01D 15/00 101 G01N 30/40 G01N 30/46

Claims (5)

(57) [Claims] An endless packed tower system in which a plurality of packed towers filled with an adsorbent are sequentially connected in series by a pipe having a shut-off valve, and a system of three or more components having different affinities for the adsorbent. (A first compartment consisting of one or more packed tower groups enriched in components having a strong affinity for the adsorbent, an intermediate between the affinity for the adsorbent) A second section consisting of one or a plurality of packed tower groups enriched with a component and one or a plurality of packed tower groups in which a component having an intermediate affinity for the adsorbent and a component having the strong affinity are mixed. The third step comprising the remaining packed tower group including one or a plurality of packed tower groups enriched with a component having a low affinity for is divided into the following, and the following steps are alternately repeated in the order of Or,
, A chromatographic separation method characterized by repeating in the order of, in the state where the shut-off valve between the second section and the third section is closed to shut off the circulation of the fluid in the entire system, the filling located immediately downstream of the shut-off valve While supplying the raw material fluid from the inlet of the column, performing an operation of flowing out the fraction enriched in the intermediate component of the affinity from the outlet of any of the packed columns in the second section,
Step of shifting the distribution of the first section to the third section to the downstream side by at least one packed tower. Following the above-described step, with the shutoff valve between the shifted third section and the first section closed, An operation of discharging the fraction enriched in the high affinity component from the outlet of the most downstream packed tower of the first compartment while supplying the desorbent fluid from the inlet of the packed tower located at the most upstream of one compartment. And an operation of flowing out the fraction enriched in the component having a low affinity from the outlet of the packed tower located at the most downstream position of the third section. In synchronism with the shift to the side by one packed column, the same operation is performed by lowering the supply position of the desorbent fluid, the extraction position of each fraction, and the position of the shut-off valve to shut off by one packed column. Step of repeating a predetermined number of times Following the above steps, the third section and the first section With the shut-off valve between the fractions closed, while supplying the desorbent fluid from the inlet of the packed tower located at the most upstream of the first section, the above affinity of the affinity is supplied from the outlet of the packed tower at the most downstream of the first section. Discharging the fraction enriched in the strong component, discharging the fraction enriched in the low affinity component from the outlet of the packed tower located at the most downstream position of the third compartment, Draining the fraction enriched in the intermediate component having the above-mentioned affinity from the outlet of the packed tower located at the most downstream position of the first column. In synchronism with the shift to the side by one packed column, the same operation is performed by lowering the supply position of the desorbent fluid, the extraction position of each fraction, and the position of the shut-off valve to shut off by one packed column. A step of repeating a predetermined number of times. 2. The process of claim 1, wherein the desorbent fluid is supplied from the inlet of the most upstream packed tower in the first section, and the affinity of the adsorbent for the adsorbent is obtained from the outlet of the most downstream packed tower in the first section. Discharging the fraction enriched in the strong component, and / or discharging the fraction enriched in the component having a low affinity for the adsorbent from the outlet of the packed tower at the most downstream position in the third section. A chromatographic separation method which is carried out simultaneously or sequentially. 3. The method according to claim 1, wherein, in the step (a) or (b), any one of the shut-off valves in the system is closed so as to block the flow of fluid from the second section to the third section. While supplying the raw material fluid from the inlet of any of the packed towers located on the upstream side in the third section located downstream of the shutoff valve, it is located on the downstream side in the second section located upstream of the shutoff valve. An operation of allowing the fraction enriched in the intermediate component to flow out from the outlet of any of the packed towers is performed, and the first section to the third section are performed.
A method of shifting the distribution of the compartments to the downstream side by at least one packed column. 4. The filling located at the most upstream position of the first section with the shut-off valve between the third section and the first section closed before and / or after the step of any one of claims 1 to 3. Draining the high-affinity component-enriched fraction from the outlet of the packed tower at the most downstream side of the first section while supplying the desorbent fluid from the inlet of the tower; While supplying the desorbent fluid from the inlet of the packed tower located, the operation of discharging the fraction enriched in the low affinity component from the outlet of the packed tower located at the most downstream side of the third section is performed simultaneously. A chromatographic separation method comprising performing these operations sequentially, or performing these operations simultaneously, and further performing at least one of these operations sequentially. 5. The method according to claim 1, wherein
Prior to the operation of each of the steps to be repeatedly performed, or the step and the step to be performed subsequently, in the state where all the shut-off valves in the system are opened, the uppermost stream of the first section While the desorbent fluid is supplied from the inlet of the packed tower located at the bottom of the first section, the fraction-enriched component having a strong affinity for the adsorbent is discharged from the outlet of the packed tower located at the most downstream of the first section. A chromatographic separation method comprising: