JP3590088B2 - Simulated moving bed type chromatographic separation method and simulated moving bed type chromatographic separation apparatus - Google Patents

Description

[0001]
[Industrial applications]
The present invention relates to a simulated moving bed type chromatographic separation method and a simulated moving bed type chromatographic separation apparatus.
[0002]
[Prior Art and Problems to be Solved by the Invention]
A conventional chromatographic separation method using a simulated moving bed type chromatograph is an endless method in which a plurality of columns containing a packing material are connected in series, and the front end and the rear end of the columns are connected by a fluid passage. The raw material-containing solution and the eluent containing the raw material which is the mixture of the components to be separated are introduced into the packed bed in which the liquid is circulated in one direction, and the liquid containing the separated components at the same time And a liquid containing other components. The packed bed in the simulated moving bed type chromatographic separator has an eluent inlet, a liquid containing an easily adsorbed substance (extract; (Rich solution), material-containing solution inlet, and liquid (raffinate; non-adsorbent-rich solution) containing a substance that is hardly adsorbed are arranged in this order along the liquid flow direction. It is, and these inlet and withdrawal points are adapted to be moved intermittently sequentially in the flow direction of the fluid while maintaining their relative positional relationship in the circulation flow path.
[0003]
As a technique for appropriately monitoring the state of separation of substances inside the simulated moving bed type chromatographic separation apparatus, there is a method described in JP-A-4-131104.
[0004]
The method described in this publication is to maintain the purity by measuring the concentration of the separated component obtained and controlling the time for intermittently moving the positions of the inlet and outlet of the fluid in the column. I do.
[0005]
However, the method described in the above publication is a method of controlling the time for intermittently moving the positions of the inlet and the outlet of the fluid so as to suppress the change in the concentration pattern. Purification alone cannot maintain the purity, and the use of non-adsorbate in the adsorption step in the simulated moving bed type chromatographic separation apparatus and reduction of the solvent used unless the adsorbate is desorbed properly in the desorption step The purity of the components obtained cannot be controlled.
[0006]
The present invention has been made based on the above circumstances. That is, an object of the present invention is to provide a simulated moving bed type chromatographic separation method and a simulated moving bed which can appropriately perform the adsorption of non-adsorbates in the adsorption step and the desorption of adsorbates in the desorption step in the simulated moving bed type chromatographic separation apparatus. An object of the present invention is to provide an apparatus for chromatographic separation. An object of the present invention is to provide a simulated moving bed type chromatographic separation method and a simulated moving bed type chromatographic separation apparatus capable of reducing the amount of eluent used and maintaining high purity of the obtained components in a simulated moving bed type chromatographic separation apparatus. An object of the present invention is to provide a separation device.
[0007]
[Means for Solving the Problems]
In order to achieve the above object, the present inventor studied and found that, in a simulated moving bed type chromatographic separation apparatus, a detector for detecting the concentration of a solute was provided at one or both of a raffinate outlet and an extract outlet. Based on the waveform of the electric signal output from the detector, the time interval (also referred to as step time) for switching the inlet and outlet of the liquid into the fluid passage in the simulated moving bed type chromatographic separation apparatus is adjusted. By doing so, the present inventors have found that it is possible to reduce the amount of eluent used and to maintain high purity of the obtained components, and have reached the present invention.
[0008]
[Means for Solving the Problems]
A first aspect of the present invention for achieving the above object is a circulating fluid flow path in which a plurality of columns containing a packing material for separation are connected endlessly, and a fluid can be forcedly circulated in one direction inside. A raw material solution inlet for introducing a raw material solution, a raffinate outlet for extracting a non-adsorbate-rich solution from the circulating fluid flow path, an eluent inlet for introducing an eluent, and an extract for extracting an adsorbate-rich solution And the extraction port are connected in this order along the flow direction of the fluid, and the raw material solution introduction port, the raffinate extraction port, the eluate introduction port and the extract extraction port are intermittently arranged in the flow direction of the circulating fluid. In the simulated moving bed type chromatographic separation method of moving,
Measuring the concentration of the solute in the raffinate extracted from the raffinate outlet with a raffinate concentration detector, and / or measuring the concentration of the solute in the extract extracted from the extract outlet with an extract concentration detector; An electrical signal waveform and / or an extra signal corresponding to the concentration of the solute in the raffinate output from the raffinate concentration detector G Based on the electrical signal waveform corresponding to the concentration of the solute in the extract, which is output from the concentration detector, The electrical signal waveform corresponding to 0% solute concentration in the raffinate matches the baseline at the beginning of the step time and / or the electrical signal waveform corresponding to 0% solute concentration in the extract So that at the end of the step time matches the baseline A simulated moving bed type chromatographic separation method characterized by controlling the flow rate of the eluent flowing through the circulation fluid flow path to an optimum flow rate,
The invention according to claim 2 is a circulating fluid flow path that can endlessly connect a plurality of columns containing the packing material for separation and forcefully circulate the fluid in one direction inside,
A raw material solution inlet for introducing the raw material solution into the circulating fluid flow path, a raffinate discharge port for extracting a non-adsorbate-rich solution from the circulating fluid flow path, which is arranged in the following order along the flow direction of the fluid, An eluent inlet for introducing the eluent and an extract outlet for extracting a solution rich in adsorbate,
Switching means for performing switching such that the eluent inlet, extract outlet, raw material solution inlet, and raffinate outlet are intermittently moved by one column along the flow direction of the fluid,
A raffinate concentration detector which is provided at a raffinate outlet and outputs a raffinate detection signal corresponding to the concentration of solute in the raffinate, and / or an extract which is provided at the extract outlet and which corresponds to the concentration of solute in the extract An extract concentration detector that outputs a detection signal,
Based on the waveform of the raffinate detection signal output from the raffinate concentration detector and / or the waveform of the extract detection signal output from the extract concentration detector, The electrical signal waveform corresponding to 0% solute concentration in the raffinate matches the baseline at the beginning of the step time and / or the electrical signal waveform corresponding to 0% solute concentration in the extract So that at the end of the step time matches the baseline An arithmetic processing unit for determining an optimal flow rate of the eluent in the circulating fluid flow path,
By inputting a control signal output from the arithmetic processing unit, a flow rate adjusting means for adjusting the flow rate of the eluent in the circulating fluid flow path
A simulated moving bed type chromatographic separation apparatus characterized by having
The invention according to claim 3 is a circulating fluid flow path capable of connecting a plurality of columns containing a packing material for separation endlessly and forcibly circulating a fluid in one direction inside,
A raw material solution inlet for introducing the raw material solution into the circulating fluid flow path, a raffinate discharge port for extracting a non-adsorbate-rich solution from the circulating fluid flow path, which is arranged in the following order along the flow direction of the fluid, An eluent inlet for introducing the eluent and an extract outlet for extracting a solution rich in adsorbate,
Switching means for performing switching such that the eluent inlet, extract outlet, raw material solution inlet, and raffinate outlet are intermittently moved by one column along the flow direction of the fluid,
A raffinate concentration detector that is provided at the raffinate extraction port and outputs a raffinate detection signal corresponding to the concentration of the solute in the raffinate;
Based on the waveform of the raffinate detection signal output from the raffinate concentration detector The electrical signal waveform corresponding to 0% solute concentration in the raffinate matches the baseline at the beginning of the step time, An arithmetic processing unit for determining an optimal flow rate of the eluent in the circulating fluid flow path,
A circulating pump for inputting a control signal output from the arithmetic processing unit and adjusting the flow rate of the fluid flowing through the circulating fluid flow path to suction and discharge the fluid;
A raffinate extraction amount adjusting means for inputting a control signal output from the arithmetic processing unit and adjusting the extraction amount of the raffinate extracted from the raffinate extraction outlet;
A simulated moving bed type chromatographic separation apparatus characterized by having
The invention according to claim 4 is a circulating fluid flow path that can endlessly connect a plurality of columns containing the packing material for separation and can forcefully circulate fluid in one direction,
A raw material solution inlet for introducing the raw material solution into the circulating fluid flow path, a raffinate discharge port for extracting a non-adsorbate-rich solution from the circulating fluid flow path, which is arranged in the following order along the flow direction of the fluid, An eluent inlet for introducing the eluent and an extract outlet for extracting a solution rich in adsorbate,
Switching means for performing switching such that the eluent inlet, extract outlet, raw material solution inlet, and raffinate outlet are intermittently moved by one column along the flow direction of the fluid,
An extract concentration detector that is provided at the extract outlet and outputs an extract detection signal corresponding to the concentration of the solute in the extract,
Based on the waveform of the extract detection signal output from the extract concentration detector , So that the electrical signal waveform corresponding to 0% solute concentration in the extract matches the baseline at the end of the step time, An arithmetic processing unit for determining an optimal flow rate of the eluent in the circulating fluid flow path,
An eluent introduction amount adjusting means for inputting a control signal output from the arithmetic processing unit and adjusting an introduction amount of the eluent introduced from the eluent introduction port,
An input control signal output from the arithmetic processing unit, an extract extraction amount adjusting means for adjusting the extraction amount of the extract extracted from the extract extraction outlet,
A simulated moving bed type chromatographic separation apparatus characterized by having
The invention according to claim 5, wherein a plurality of columns accommodating the packing material for separation are connected endlessly, and a circulating fluid flow path capable of forcibly circulating the fluid in one direction inside,
A raw material solution inlet for introducing the raw material solution into the circulating fluid flow path, a raffinate discharge port for extracting a non-adsorbate-rich solution from the circulating fluid flow path, which is arranged in the following order along the flow direction of the fluid, An eluent inlet for introducing the eluent and an extract outlet for extracting a solution rich in adsorbate,
Switching means for performing switching such that the eluent inlet, extract outlet, raw material solution inlet, and raffinate outlet are intermittently moved by one column along the flow direction of the fluid,
A raffinate concentration detector that is provided at the raffinate extraction port and outputs a raffinate detection signal corresponding to the concentration of the solute in the raffinate;
An extract concentration detector that is provided at the extract outlet and outputs an extract detection signal corresponding to the concentration of the solute in the extract,
Based on the waveform of the raffinate detection signal output from the raffinate concentration detector and the extract detection signal output from the extract concentration detector The electrical signal waveform corresponding to the 0% solute concentration in the raffinate matches the baseline at the beginning of the step time, and the electrical signal waveform corresponding to the 0% solute concentration in the extract is To match the baseline at the end of the step time, An arithmetic processing unit for determining an optimal flow rate of the eluent in the circulating fluid flow path,
A circulating pump for inputting a control signal output from the arithmetic processing unit and adjusting the flow rate of the fluid flowing through the circulating fluid flow path to suction and discharge the fluid;
A raffinate extraction amount adjusting means for inputting a control signal output from the arithmetic processing unit and adjusting the extraction amount of the raffinate extracted from the raffinate extraction outlet,
An eluent introduction amount adjusting means for receiving a control signal output from the arithmetic processing unit and adjusting an introduction amount of an eluent introduced from an eluent introduction port,
An input control signal output from the arithmetic processing unit, an extract extraction amount adjusting means for adjusting the extraction amount of the extract extracted from the extract extraction outlet,
It is a simulated moving bed type chromatographic separation apparatus characterized by having:
[0009]
[Action]
In the simulated moving bed type chromatographic separation apparatus according to the present invention, a circulating fluid flow path is formed by connecting a plurality of columns containing a separation packing material endlessly through a pipe such as a pipe. . A raw material solution inlet for introducing a raw material solution containing a racemic mixture of optical isomers, and a non-adsorbate-rich solution (also referred to as a raffinate) are withdrawn through the circulating fluid channel along the flow direction of the fluid. A raffinate outlet, an eluent inlet for introducing an eluent into the circulating fluid channel, and an extract outlet for extracting a solution rich in adsorbate (also referred to as extract) are provided in this order.
[0010]
When the raw material is introduced into the circulating fluid flow path from the raw material solution introduction port while circulating the fluid in one direction in the circulating fluid flow path, the raw material solution comes into contact with the packing material in the column, and the adsorbate component (easy adsorption) And a non-adsorbate component (a component that is difficult to adsorb and is also referred to as a weakly adsorbed component) as a raffinate component together with the eluent. It is extracted from the raffinate extraction port (this step is also called an adsorption step). The filler adsorbing the adsorbate component comes into contact with a part of the extract, the remaining non-adsorbate component on the filler is expelled, and the adsorbate component is concentrated (this step is also called a concentration step). .) When the filler containing the concentrated adsorbate component comes into contact with the eluent, the adsorbate component is expelled from the filler, and with the eluent, is extracted from the circulating fluid channel through the extract outlet as an extract. (This step is also called a desorption step). The packing material having substantially adsorbed only the eluent comes into contact with a part of the raffinate, and a part of the eluent contained in the packing material is recovered as an eluent recovery part (this step is also called an eluent recovery step). Is done.)
[0011]
The above-described continuous process is effective in a state where the positions of the inlet and the outlet are fixed at a certain point in time.However, when the positions of the inlets and the outlet are switched at predetermined time intervals, the same applies to each column. Each time the switching is performed, the same steps as described above are repeated.
[0012]
In the simulated moving bed chromatographic method of the present invention, an electrical signal waveform output from a raffinate concentration detector for measuring the concentration of a solute in a raffinate and / or an extract provided at a raffinate outlet. The flow rate of the eluent flowing through the circulating fluid flow path is determined based on an electrical signal waveform output from an extract concentration detector that measures the concentration of a solute in the extract, which is provided at the outlet. Control to the optimal flow rate.
[0013]
For example, when it is determined from the electrical signal waveform output from the raffinate concentration detector that the flow rate in the eluent recovery step is larger than an appropriate amount, for example, the suction and discharge amount of the circulating pump is reduced and the raffinate outlet is reduced. By increasing the amount of raffinate withdrawn, the circulating amount of the eluent can be properly maintained. Conversely, when it is determined from the electrical signal waveform output from the raffinate concentration detector that the flow rate in the eluent recovery step is smaller than an appropriate amount, for example, the suction and discharge amount of the circulation pump is increased and the raffinate extraction port is increased. By reducing the amount of raffinate withdrawn, the circulation amount of the eluent can be properly maintained.
[0014]
Also, from the electrical signal waveform output from the extract concentration detector, Flow rate is appropriate If it is determined that the amount of eluent circulated is reduced by reducing the flow rate of the eluent introduced from the eluent inlet and decreasing the amount of extract extracted from the extract outlet, for example, Can be maintained. From the electrical signal waveform output from the extract concentration detector, Flow rate is appropriate If it is determined that the amount of the eluent circulated is appropriately reduced, for example, by increasing the flow rate of the eluent introduced from the eluent inlet and increasing the amount of extract withdrawn from the extract outlet. Can be maintained.
[0015]
In the method and apparatus of the present invention, one or both of a raffinate concentration detector and an extract concentration detector can be provided.
[0016]
By providing a raffinate concentration detector or an extract concentration detector, the circulation amount of the eluent can be properly maintained, but by providing both of these concentration detectors, a more accurate eluent circulation can be achieved. The amount can be determined and the circulation amount can be maintained.
[0017]
【Example】
Hereinafter, the present invention will be described in detail.
[0018]
As shown in FIG. 1, a simulated moving bed type chromatographic separation apparatus 1 which is an embodiment apparatus of the present invention has first to eighth unit columns (also referred to as unit packed beds) 2a to 2h. The fluid outlet of the first unit column 2a and the fluid inlet of the second unit column 2b; the fluid outlet of the second unit column 2b and the fluid inlet of the third unit column 2c; The fluid inlet of the eight unit column 2h is connected to each other by a fluid passage 3a, and the fluid outlet of the eighth unit column 2h and the fluid inlet of the first unit column 2a are connected by a fluid passage 3b. A check valve 4 is provided in the fluid passage 3a connecting each unit column with the next unit column. The check valve 4 has a function of conducting fluid from one unit column to the next unit column, but preventing the reverse flow. Therefore, in this embodiment, as long as the check valve 4 has the above function, the structure thereof is not particularly limited, and a known check valve and a new check valve to be developed in the future can be used.
[0019]
In a fluid passage 3a connecting each unit column and an adjacent unit column, a branch fluid passage 3c connected to a third rotary valve 5 is connected between the fluid outlet of the unit column and the check valve 4. In other words, the third rotary valve 5 is connected to the fluid passage 3c from the fluid passage 3a connecting the first unit column 2a and the second unit column 2b, and is connected to the second unit column 2b and the third unit column 2c. And eight branch fluid passages 3c branched from the fluid passages 3a between the unit columns in the same manner. The third rotary valve 5 selects one of the eight branch fluid passages 3c, extracts the fluid from the selected fluid passage 3a, and closes the other branch fluid passage 3c. It has the function of The structure of the third rotary valve 5 is not particularly limited as long as it has such a function, and a conventionally known rotary valve and a new rotary valve to be developed in the future can be used.
[0020]
A circulation pump 6 is connected to the discharge side of the third rotary valve 5. The discharge side of the circulation pump 6 is connected to the fourth rotary valve 7 via the fluid passage 3d.
[0021]
The amount of suction and discharge of the circulation pump 6 is made variable by a control signal from a calculation control unit 12 described later.
[0022]
From the middle of the fluid passage 3d, the supply pump P ₁ The eluent is supplied via. Therefore, the fluid flowing through the fluid passage 3d and the eluent are supplied to the fourth rotary valve 7. In this embodiment, the supply pump P, which is connected to the fluid passage 3d, ₁ Is the eluent introduction path. This supply pump P ₁ Can change the supply amount of the eluent by a control signal from the operation control unit 12 described later.
[0023]
The discharge side of the fourth rotary valve 7 is divided into eight fluid passages 3e. Each of the fluid passages 3e is connected to the check valve 4 and the next one of the fluid passages connecting each unit column to the next unit column. And the fluid inlet of the unit column.
[0024]
The fourth rotary valve 7 selects one branch fluid passage 3e among the eight branch fluid passages 3e, and simultaneously closes the other branch fluid passage 3e to supply the fluid to the selected fluid passage 3e. It has a function of discharging and thereby supplying a fluid to a fluid passage 3a connecting a specific unit column and the next unit column. The structure of the fourth rotary valve 7 is not particularly limited as long as it has such a function, and a conventionally known rotary valve and a new rotary valve to be developed in the future can be used.
[0025]
In FIG. 1, reference numeral 8 denotes a first rotary valve. The first rotary valve 8 has a pump P ₂ The raw material solution containing the optical isomer mixture is supplied via. Eight fluid passages 3f are connected to the discharge side of the first rotary valve 8. Each of the fluid passages 3f is connected between the check valve 4 and the fluid inlet of the next unit column of the fluid passage connecting each unit column to the next unit column. In this embodiment, one of the eight fluid passages 3f on the discharge side of the first rotary valve 8 serves as a raw material solution introduction passage.
[0026]
The first rotary valve 8 selects one branch fluid passage 3f among the eight branch fluid passages 3f, simultaneously closes the other branch fluid passage 3f, and supplies fluid to the selected fluid passage 3f. It has a function of discharging and thereby supplying a fluid to a fluid passage 3a connecting a specific unit column and the next unit column. The structure of the first rotary valve 8 is not particularly limited as long as it has such a function, and a conventionally known rotary valve and a new rotary valve to be developed in the future can be used.
[0027]
A branch fluid passage 3g connected to the second rotary valve 9 is provided between the check valve 4 and the fluid inlet of the next unit column of the fluid passage 3a connecting this unit column to the next unit column. Is connected. According to the second rotary valve 9, eight branch fluid passages 3g branched from each of the fluid passages 3a connecting each unit column and the next unit column are connected, and one of the branch fluid passages 3g is connected. 3g is opened, and the other branch fluid passage 3g is closed. In this embodiment, one of the eight branch fluid passages 3g serves as a raffinate extraction passage. The second rotary valve 9 is connected to the pump P ₃ To discharge the fluid.
[0028]
This pump P ₃ Can change the extraction amount of the raffinate by a control signal output from an arithmetic control unit described later.
[0029]
The second rotary valve 9 selects one branch fluid passage 3g out of the eight branch fluid passages 3g, simultaneously closes the other branch fluid passage 3g, and allows the fluid to flow from the selected fluid passage 3g. It has a function of introducing and thereby discharging a fluid to a fluid passage 3g connecting a specific unit column and the next unit column. The structure of the second rotary valve 9 is not particularly limited as long as it has such a function, and a conventionally known rotary valve and a new rotary valve to be developed in the future can be used.
[0030]
The discharge port of the second rotary valve 9 has a discharge pump P ₃ , A raffinate extraction tube 11 is provided. A raffinate concentration detector RF is provided in the middle of the raffinate extraction tube 11.
[0031]
The type of the raffinate concentration detector RF is not particularly limited as long as it can detect a characteristic corresponding to the concentration of the solute in the raffinate and can output a detection signal as an electric signal. In this embodiment, a UV detector is employed as the raffinate concentration detector RF, but depending on the characteristics of the raffinate or the solute in the raffinate, for example, an ultrasonic detector, an RI detector, an infrared detector, an optical rotation A detector, a sugar content detector, an electrical conductivity detector, a thermal conductivity detector, and the like can be employed. A detection signal, which is an electric signal, is output to the arithmetic and control unit 12 from the raffinate concentration detector RF, which is a UV detector.
[0032]
The raffinate concentration detector RF outputs an electric signal corresponding to the concentration of the raffinate, for example, a voltage or a current. When the concentration of the solute in the raffinate is 0, for example, as shown in FIG. 2, if the output electric signal from the raffinate concentration detector RF matches the baseline, it is determined that the output signal is proper. I can say. This electric signal is basically 0 during the time from the moment when the second rotary valve 9 is switched to the next switching, that is, at the beginning of the step time C, and the concentration of the raffinate in the withdrawn liquid is zero. Since it rises, the signal strength (for example, voltage or current value) rises over time.
[0033]
When a large amount of solute is contained in the raffinate at the moment when the second rotary valve 9 is switched, in other words, when the amount of the eluent is too small, the intensity of the detection signal output from the raffinate concentration detector RF becomes, for example, As shown in FIG. 3, at the beginning of the step time C, it is located above the baseline. Further, when the solute is not contained in the raffinate at the moment when the second rotary valve 9 is switched, that is, when the amount of the eluent is too large, the intensity of the detection signal output from the raffinate concentration detector RF becomes, for example, As shown in FIG. 4, the detection signal rises after a certain time has elapsed from the beginning of the step time C.
[0034]
A branch fluid passage 3h connected to the fifth rotary valve 10 is further connected between the check valve 4 and the next unit column of the fluid passage 3a connecting this unit column to the next unit column. ing. According to the fifth rotary valve 10, eight branch fluid passages 3g branched from each of the fluid passages 3a connecting each unit column to the next unit column are connected, and one of the branch fluid passages 3g is connected. 3h is opened, and the other branch fluid passage 3h is closed. In this embodiment, one of the eight branch fluid passages 3h serves as an extract outlet.
[0035]
The fifth rotary valve 10 selects one of the eight branch fluid passages 3h, simultaneously closes the other branch fluid passage 3h, and transfers fluid from the selected fluid passage 3h. It has a function of introducing and thereby discharging a fluid to a fluid passage 3h connecting a specific unit column and the next unit column. The structure of the fifth rotary valve 10 is not particularly limited as long as it has such a function, and a conventionally known rotary valve and a new rotary valve to be developed in the future can be used.
[0036]
The discharge port of the fifth rotary valve 10 includes a discharge pump P ₄ An extract extraction tube 13 is provided via the.
[0037]
This discharge pump P ₄ The suction discharge amount can be varied by a control signal output from the arithmetic control unit 12 described later.
[0038]
An extract concentration detector EX is provided in the middle of the extract extraction tube 13.
[0039]
The type of the extract concentration detector EX is not particularly limited as long as it can detect a characteristic corresponding to the concentration of a solute in the extract and can output a detection signal as an electric signal. In this embodiment, a UV detector is employed as the extract concentration detector EX. However, depending on the characteristics of the extract or the solute in the extract, for example, an ultrasonic detector, an RI detector, an infrared detector, etc. Detectors, optical rotation detectors, sugar content detectors, electrical conductivity detectors, thermal conductivity detectors, and the like can be employed. A detection signal, which is an electric signal, is output from the extract concentration detector EX, which is a UV detector, to the arithmetic and control unit 12.
[0040]
The extract concentration detector EX outputs an electric signal corresponding to the concentration of the extract, for example, a voltage or a current. Then, at the moment when the fifth rotary valve 10 is switched, the concentration of the solute in the extract is the maximum, and the concentration of the solute in the extract decreases with time and becomes zero. At the moment when the concentration of the solute in the extract becomes zero, the fifth rotary valve 10 is switched again. Assuming that the period during which the fifth rotary valve 10 is switched is a step type C, if the concentration of the solute in the extract is appropriate during the period of the step time C, for example, as shown in FIG. The density value matches the baseline.
[0041]
When the amount of eluent is too small during the extract immediately before switching the fifth rotary valve 10, in other words, when the flow rate in the desorption step is too small, the intensity of the detection signal output from the raffinate concentration detector RF is, for example, as shown in FIG. At the end of the step time C, it is located above the baseline. When the amount of eluent in the extract immediately before switching the fifth rotary valve 10 is large, in other words, when the amount of eluent is too large, the intensity of the detection signal output from the extract concentration detector EX becomes For example, as shown in FIG. 7, the detection signal rises after a certain time has elapsed from the beginning of the step time C.
[0042]
The arithmetic control unit 12 receives the electric signals from the raffinate concentration detector RF and the extract concentration detector EX, and, based on the detection signal output from the raffinate concentration detector RF, determines the eluent flowing through Of the circulation pump 6, pump P ₁ , Pump P ₃ , And pump P ₄ And outputs a control signal for driving.
[0043]
The control of the eluent flow rate based on the signal waveform output from the raffinate concentration detector RF is performed, for example, as follows.
[0044]
(1) For example, the waveform of the detection signal output from the raffinate concentration detector RF provided for measuring the concentration of the solute in the raffinate flowing through the raffinate extraction pipe 11 is, for example, as shown in FIG. If not reached, the arithmetic and control unit that has received the detection signal determines that the flow rate of the fluid in the eluate recovery step is excessive, and outputs a control signal to the circulation pump 6 to reduce the suction and discharge amount of the circulation pump 6. And outputs a control signal to the second rotary valve 9 so that the pump P ₃ To increase the amount of suction and discharge. Where P ₃ Is required to be the same as the amount by which the amount of suction and discharge of the circulation pump 6 is reduced.
[0045]
At this stage, the suction / discharge amount of the circulation pump 6 and the pump P ₃ May be roughly controlled.
[0046]
Suction and discharge amount of circulation pump 6 and pump P ₃ The approximate control of the suction and discharge amount can be performed as follows, for example.
[0047]
For example, the arithmetic and control unit 12 determines the value A of the waveform of the detection signal output from the raffinate concentration detector RF when the second rotary valve 9 is switched (this value corresponds to the concentration of the solute in the raffinate). Table between the difference (A−B) between the pressure A and the baseline B and the suction / discharge amount D of the circulation pump 6, and the difference (A−B) between the value A and the baseline B and the suction / discharge amount E of the pump 9 Is stored in advance, and the value A at the time of switching the second rotary valve 9 in the waveform of the detection signal output momentarily from the raffinate concentration detector RF is stored. ₁ Are compared with the correspondence table, the circulation pump 6 and the pump P ₃ Is determined, and the circulation pump 6 and the pump P are adjusted so that the determined suction and discharge amount is attained. ₃ To output the drive signal.
[0048]
(2) The circulation pump 6 and the pump P ₃ Of the raffinate withdrawal from the raffinate withdrawal pipe 11 and the flow through the fluid passage 3c.
[0049]
After the change in the circulation amount, the arithmetic and control unit 12 determines whether or not the value A at the time of switching the second rotary valve 9 in the waveform of the detection signal output from the raffinate concentration detector RF is above the baseline. I do. When it is determined that the value A is above the baseline, the procedure (1) is repeated.
[0050]
Then, the flow rate of the fluid in the fluid passage 3c and the extraction amount of the raffinate are varied, and the above procedure (1) is repeated until the value A falls below the baseline.
[0051]
When the arithmetic and control unit 12 determines that the value A is below the baseline, the process proceeds to the next step (3).
[0052]
(3) When the waveform of the detection signal output from the raffinate concentration detector RF changes as shown in FIG. 4 after the change in the circulation amount, the arithmetic and control unit 12 is output from the raffinate concentration detector RF momentarily. In the step time c of the latest signal waveform among the detection signals, a period b from the time when the signal waveform rises from the baseline to the end of the step time is counted. Then, the arithmetic control unit 12 calculates a / c, and when the result exceeds a predetermined allowable maximum value, for example, 0.5, the suction / discharge amount of the circulation pump 6 becomes c / b times the suction / discharge amount up to that time. Thus, a control signal is output to the circulation pump 6 so as to increase the flow rate in the fluid passage 3c, and at the same time, the flow rate of the raffinate in the raffinate extraction pipe 11 is decreased by the increase in the flow rate in the fluid passage 3c. Like the pump P ₃ Control signal for controlling the driving of the pump P ₃ Output to
[0053]
The predetermined maximum allowable value can be arbitrarily determined, and is usually 0.5, preferably 0.3, and more preferably 0.1.
[0054]
(4) a / c is calculated after the flow rate in the fluid passage 3c and the extraction amount in the raffinate extraction pipe 11 are changed by a control signal from the arithmetic control unit 12, and the result is reduced to a predetermined allowable maximum value or less. Repeat the above step (3) until the above is completed.
[0055]
(5) When the calculation result of a / c becomes smaller than a predetermined allowable minimum value, for example, less than 0.01 by the procedure of the above (3) or (4), the suction / discharge amount of the circulation pump 6 becomes the previous suction / discharge amount. (Where d is a number greater than 1), that is, a control signal is output to the circulation pump 6 so that the flow rate in the fluid passage 3c decreases, and at the same time, the raffinate is extracted. The pump P is set so that the flow rate of the raffinate in the pipe 11 is increased by the decrease in the flow rate in the fluid passage 3c. ₃ Control signal for controlling the driving of the pump P ₃ Output to
[0056]
The predetermined allowable minimum value can be arbitrarily determined, and is usually 0.01.
[0057]
(6) The procedure of (5) is repeated so that the calculation result of a / c exceeds a predetermined allowable minimum value, for example, 0.01.
[0058]
By executing the above procedure as shown in FIG. 8, the amount of raffinate withdrawn through the raffinate withdrawing pipe 11 is such that a / c at step time C is 0.01 to 0.5, preferably 0.01 to 0.5. .3, more preferably in the range of 0.01 to 0.1.
[0059]
The control of the eluent flow rate based on the signal waveform output from the extract concentration detector EX is performed, for example, as follows.
[0060]
(1) For example, as shown in FIG. 6, the waveform of the detection signal output from the extract concentration detector EX provided for measuring the concentration of the solute in the extract flowing through the extract extraction tube 13 is as shown in FIG. When the detection signal is not reached, the arithmetic and control unit that has received the detection signal determines that the flow rate of the fluid in the desorption process is insufficient, and ₁ Output a control signal to the pump P ₁ Of the pump P ₄ Output a control signal to the pump P ₄ To increase the amount of suction and discharge.
[0061]
Pump P at this stage ₁ Suction and discharge amount and pump P ₄ May be roughly controlled.
[0062]
Pump P ₁ Suction and discharge amount and pump P ₄ The approximate control of the suction and discharge amount can be performed as follows, for example.
[0063]
For example, the arithmetic and control unit 12 determines a value A ′ (when this value is in the middle of the extraction) of the waveform of the detection signal output from the extract concentration detector EX when the rotary valves 5, 7, 8, 9, and 10 are switched. (A′−B ′) between the base line B ′ and the pump P ₁ Table of the relationship between the suction and discharge amount D ′, and the difference (A′−B ′) between the value A ′ and the baseline B ′ and the pump P ₁ Is stored in advance in correspondence with the eluent supply amount E of the rotary valves 5, 7, 8, 9, and 10 in the waveform of the detection signal output from the extract concentration detector EX every moment. By comparing the value A ′ with the correspondence table, the pump P ₁ And pump P ₄ Is determined, and the pump P is adjusted so that the determined suction and discharge amount is attained. ₁ And pump P ₄ To output the drive signal.
[0064]
(2) According to the procedure (1), the pump P ₁ And pump P ₄ And the amount of extraction in the extract extraction pipe 13 and the amount of circulation in the fluid passage 3e change.
[0065]
After the change in the circulation amount, the pump P in the waveform of the detection signal output from the extract concentration detector EX ₄ The arithmetic and control unit 12 determines whether or not the value a at the time of switching is above the baseline. When it is determined that the value a is above the baseline, the procedure (1) is repeated.
[0066]
Then, the flow rate of the fluid in the fluid passage 3e and the extraction amount of the extract are varied, and the above procedure (1) is repeated until the value a becomes lower than the baseline.
[0067]
When the arithmetic and control unit 12 determines that the value a is below the baseline, the process proceeds to the next step (3).
[0068]
(3) When the waveform of the detection signal output from the extract concentration detector EX changes as shown in FIG. 7 after the change in the circulation amount, the arithmetic and control unit 12 outputs the output from the extract concentration detector EX every moment. The period (b) from the beginning of the step time to the time when the signal waveform reaches the base line is counted from the step time (c) in the latest signal waveform of the detected signal. The arithmetic control unit 12 calculates (a) / (c), and when the result exceeds a predetermined allowable maximum value, for example, 0.5, the pump P ₁ So that the suction / discharge amount of the pump P becomes equal to (b) / (c) times the previous suction / discharge amount, that is, the flow rate in the fluid passage 3e decreases. ₁ At the same time, the pump P is controlled so that the amount of extract extracted from the extract extraction pipe 13 is reduced by the decrease in the flow rate in the fluid passage 3c. ₄ Control signal for controlling the driving of the pump P ₄ Output to
[0069]
The predetermined maximum allowable value can be arbitrarily determined, and is usually 0.5, preferably 0.3, and more preferably 0.1.
[0070]
(4) (a) / (c) is calculated after the flow rate in the fluid passage 3e and the extraction amount in the extract extraction pipe 13 are changed by the control signal from the arithmetic control unit 12, and the result is a predetermined value. The above procedure (3) is repeated until the value becomes equal to or less than the allowable maximum value.
[0071]
(5) When the calculation result of (a) / (c) becomes smaller than a predetermined allowable minimum value, for example, less than 0.01 by the procedure of (3) or (4), the pump P ₁ Pump e so that the suction / discharge amount of the pump P becomes e times (e is a number larger than 1) the previous suction / discharge amount, that is, the flow rate in the fluid passage 3e increases. ₁ To the pump P so that the amount of extract flowing through the extract extraction pipe 13 is increased at the same time by the increase in the flow rate in the fluid passage 3e. ₄ Control signal for controlling the driving of the pump P ₄ Output to
[0072]
The predetermined allowable minimum value can be arbitrarily determined, and is usually 0.01.
[0073]
(6) The procedure of (5) is repeated so that the calculation result of (a) / (c) exceeds a predetermined allowable minimum value, for example, 0.01.
[0074]
As shown in FIG. 9, by executing the above procedure, the amount of extracted extract flowing through the extract extraction tube 13 is (a) / (c) at step time C is preferably 0.01 to 0.5, preferably Is adjusted to be in the range of 0.01 to 0.3, more preferably 0.01 to 0.1.
[0075]
The simulated moving bed type chromatographic separation apparatus 1 having the above configuration will be described in more detail.
[0076]
In the simulated moving bed type chromatographic separation apparatus 1 shown in FIG. 1, for example, the first to fifth rotary valves 5, 7, 8, 9, 10 are assumed to be set in the following state.
[0077]
That is, of the eight fluid passages 3e in the fourth rotary valve 7, the liquid passage 3b connecting the eighth unit column 2h and the first unit column 2a is opened, and the other liquid passages 3a are opened. One fluid passage 3e is selected so that is closed, and for the fifth rotary valve 10, a branch fluid passage branched from the fluid passage 3a connecting the first unit column 2a and the second unit column 2b. The branch fluid passage 3h is selected so that only 3h is in the open state and the other branch fluid passage 3h is in the closed state. For the first rotary valve 8, the third unit column 2c and the fourth unit column 2d are connected. The fluid passage 3f is selected such that only the fluid passage 3f connected to the communicating fluid passage 3a is opened, and the other fluid passages 3f are closed. In other words, only the branch fluid passage 3g branched from the fluid passage 3a connecting the seventh unit column 2g and the eighth unit column 2h is open, and the other branch fluid passage 3g is closed. The passage 3g is selected, and the third rotary valve 5 is set so that only the fluid passage 3c between the eighth unit column 2h and the check valve 4 is opened, and the other fluid passages 3c are closed. The passage 3c is selected.
[0078]
In this state, the first unit column 2a to the eighth unit column 2h, the fluid passage branched from the fluid passage between the fluid outlet of the eighth unit column 2h and the check valve and communicating with the third rotary valve 5 3c, a fluid passage 3d, a fourth rotary valve 7, a fluid passage 3e communicating from the fourth rotary valve 7 to the fluid passage 3c, and a circulating fluid flow path surrounding the fluid passage 3c in this order.
[0079]
The switching timing of the first to fifth rotary valves 5, 7, 8, 9, 10 is controlled by a control command signal from the arithmetic and control unit 12.
[0080]
Each of the unit columns 2a to 2h contains a filler capable of adsorbing a component to be separated.
[0081]
As the filler, various known fillers for isomer separation can be used. For example, examples of the filler for separating optical isomers include a filler for optical resolution using an optically active high molecular compound and a low molecular compound having optical resolution ability. Examples of the optically active polymer compound include a polysaccharide derivative (eg, an ester or carbamate of cellulose or amylose), a polyacrylate derivative, or a filler in which a polyamide derivative is supported on silica gel, or the polymer itself without using silica gel. Can be mentioned. Examples of the low molecular weight compound having optical resolution ability include an amino acid derivative, a crown ether or a derivative thereof, and a cyclodextrin or a derivative thereof. These low molecular compounds are generally used by being supported on an inorganic carrier such as silica gel, alumina, zirconia, titanium oxide, silicate and diatomaceous earth, and an organic carrier such as polyurethane, polystyrene and polyacrylic acid derivatives.
[0082]
Commercially available fillers can also be used. For example, CHIRALCEL OB (registered trademark), CHIRALCEL OD (registered trademark), CROWNPAK CR (+) (registered trademark), CHIRALCEL CA-1 manufactured by Daicel Chemical Industries, Ltd., respectively. (Registered trademark), CHIRALCEL OA (registered trademark), CHIRALCEL OK (registered trademark), CHIRALCEL OJ (registered trademark), CHIRALCEL OC (registered trademark), CHIRALCEL OF (registered trademark), CHIRALCEL OG (registered trademark), CHIRALPAK WH ( (Registered trademark), CHIRALPAK WM (registered trademark), CHIRALPAK WE (registered trademark), CHIRALPAK OT (+) (registered trademark), CHIRALPAK OP (+) (registered trademark), CHIRALPAK S (R), can be cited as a preferred example CHIRALPAK AD (registered trademark).
[0083]
The average particle size of the filler packed in each of the unit columns 2a to 2h varies variously depending on the type of the component to be separated, the volume flow rate of the solvent flowing through each unit column, and the like. , Usually 1 to 300 µm, preferably 5 to 100 µm. However, if the pressure loss in the simulated moving bed is to be suppressed small, it is desirable to adjust the average particle size of the filler to 15 to 75 μm. When the average particle size of the filler is within the above range, pressure loss in the simulated moving bed can be reduced, for example, 10 kgf / cm. ² The following can also be suppressed. On the other hand, as the average particle size of the filler increases, the theoretical number of adsorption stages decreases. Therefore, the average particle size of the filler is usually 15 to 75 μm, only considering that a practical theoretical plate number is achieved.
[0084]
Examples of the eluent supplied to the fourth rotary valve 7 include alcohols such as methanol, ethanol, and isopropanol; hydrocarbons such as hexane; organic solvents such as ethers, esters, ketones, and amides; An aqueous solution containing a salt such as an aqueous chlorate solution can be used. Which eluent is preferable is appropriately determined depending on the type of component or compound to be separated.
[0085]
The raw material solution supplied to the first rotary valve 8 is not particularly limited as long as it is a substance that needs to be separated. For example, various compounds used in the fields of medicine, agricultural chemicals, food, feed, flavors, and the like, for example, Examples include thalidomide of pharmaceuticals, EPN which is an organic phosphorus pesticide, monosodium glutamic acid which is a chemical seasoning, menthol which is a flavor, and further include optically active alcohols and optically active esters. be able to.
[0086]
In the simulated moving bed type chromatographic separation apparatus shown in FIG. 1, when the first to fifth rotary valves 5, 7, 8, 9, 10 are in the above-mentioned open state and closed state, the eighth unit column 2h and the first unit When the eluent is supplied to the fluid passage 3b communicating with the column 2a via the fourth rotary valve 7, the check valve 4 exhibits a backflow prevention function, and the fluid discharged from the eighth unit column 2h is The fluid is led out to the third rotary valve 5 through the fluid passage 3c, and is led to the first unit via the third rotary valve 5, the circulation pump 6, the fourth rotary valve 7, the fluid passage 3e, and the fluid passage 3b. It is introduced into the column 2a.
[0087]
In the simulated moving bed type chromatographic separation apparatus shown in FIG. 1, (1) As the adsorption step, the raw material mixture comes into contact with the filler by the fourth unit column 2d to the seventh unit column 2g, and the components easily adsorbed on the filler. The (strongly adsorbed component) is adsorbed, and the other component (weakly adsorbed component) that is difficult to adsorb is collected as a raffinate together with the eluate. (2) As a concentration step, the second unit column 2b to the third unit column 2c The filler adsorbing the strongly adsorbed component comes into contact with a part of the extract, the weakly adsorbed component remaining on the filler is expelled, the strongly adsorbed component is concentrated, and (3) the first unit is used as a desorption step. By the column 2a, the packing material containing the concentrated strongly adsorbed component is brought into contact with the eluent, and the strongly adsorbed component is displaced from the packing material, and is discharged from the simulated fluidized bed as an extract with the eluent. (4) In the eluent recovery step, the filler adsorbing substantially only the eluent is brought into contact with a part of the raffinate by the eighth unit column 2h, and a part of the eluate contained in the filler is removed. Collected as eluate recovery.
[0088]
In such a simulated moving bed type chromatograph, the supply position of the eluent, the supply position of the raw material solution, and each extraction position are controlled by operating the first to fifth rotary valves 5, 7, 8, 9, and 10 at regular time intervals. It is moved by one unit column in the flow direction of the solvent.
[0089]
Therefore, in the second stage, the desorption step is performed by the second unit column 2b, the concentration step is performed by the third unit column 2c and the fourth unit column 2d, the adsorption step is performed by the fifth unit columns 2e to 82h, and the elution is performed by the first unit column 2a. Each of the liquid recovery steps is performed.
[0090]
In this case, a detection signal is output from the raffinate concentration detector RF to the arithmetic and control unit 12, and the arithmetic and control unit 12 calculates and monitors the concentration of the solute in the raffinate. Further, a detection signal is output from the extract concentration detector EX to the arithmetic control unit 12, and the arithmetic control unit 12 determines the concentration of the solute in the extract and monitors the concentration. Based on the result of monitoring the raffinate and the result of monitoring the extract, control command signals are output from the first to fifth rotary valves 5, 7 to 10 from the arithmetic and control unit 12, and the time of the step time is adjusted.
[0091]
By performing such an operation, each step is shifted by one unit column, and a separation process of a mixture of similar compounds is continuously and efficiently achieved.
[0092]
Further, in this simulated moving bed type chromatographic separation apparatus 1, since the amount of fluid extracted from each unit column via the fluid passage 3b is constant, the discharge in the circulation pump 6 connected to the third rotary valve 5 is controlled. It is not necessary to adjust the amount every time the third rotary valve 5 is switched.
[0093]
【The invention's effect】
According to the method of the present invention, by continuously monitoring the concentration of the components in the solution withdrawn from the packed bed of the simulated moving bed chromatograph, the adsorption of the non-adsorbate in the adsorption step and the adsorption of the adsorbate in the desorption step are performed. Desorption can be performed appropriately. In particular, by monitoring the solute in the raffinate extracted from the raffinate extraction port, the adsorption of non-adsorbate in the adsorption step can be performed efficiently and optimally. By monitoring the solute in the extract withdrawn from the extract outlet, the adsorbate can be efficiently desorbed in an optimal state in the desorption step.
[Brief description of the drawings]
FIG. 1 is a conceptual explanatory view of a simulated moving bed type chromatographic separation apparatus according to the present invention.
FIG. 2 is a graph showing a temporal change of numerical data output from a detector connected to a raffinate outlet.
FIG. 3 is a graph showing a temporal change in numerical data output from a detector connected to a raffinate outlet.
FIG. 4 is a graph showing a temporal change of numerical data output from a detector connected to a raffinate outlet.
FIG. 5 is a graph showing a temporal change of numerical data output from a detector connected to an extract outlet.
FIG. 6 is a graph showing a temporal change of numerical data output from a detector connected to an extract outlet.
FIG. 7 is a graph showing a temporal change of numerical data output from a detector connected to an extract outlet.
FIG. 8 is a flow chart showing a method for controlling the suction / discharge amount of the circulation pump and the raffinate withdrawal amount based on the concentration of the solute in the raffinate.
FIG. 9 is a flowchart showing a method of controlling the suction and discharge amount of a pump based on the concentration of a solute in an extract.
[Explanation of symbols]
DESCRIPTION OF SYMBOLS 1 ... Simulated moving bed type chromatographic separation apparatus, 2a-2h ... Unit column, 3a-3h ... Fluid passage, 4 ... Check valve, 5 ... Third rotary valve, 6 ...・ Circulation pump, 7 ・ ・ ・ 4th rotary valve, 8 ・ ・ ・ 1st rotary valve, 9 ・ ・ ・ 2nd rotary valve, 10 ・ ・ ・ 5th rotary valve, 11 ・ ・ ・ Raffinate extraction pipe, 12 ・Calculation control unit, 13: extract extraction tube, RF: raffinate concentration detector, EX: extract concentration detector

Claims (5)

A raw material solution inlet for introducing a raw material solution into a circulating fluid flow path that connects endlessly a plurality of columns containing a packing material for separation, and through which a fluid can be forcedly circulated in one direction; A raffinate outlet for extracting the non-adsorbate-rich solution from the channel, an eluent inlet for introducing the eluent, and an extract outlet for extracting the adsorbate-rich solution are connected in this order along the flow direction of the fluid, And, in the simulated moving bed type chromatographic separation method in which the raw material solution inlet, the raffinate outlet, the eluent inlet and the extract outlet are intermittently moved in the flow direction of the circulating fluid,
Measuring the concentration of the solute in the raffinate withdrawn from the raffinate outlet with a raffinate concentration detector, and / or measuring the concentration of the solute in the extract withdrawn from the extract outlet with an extract concentration detector; where output from the raffinate concentration detector, where output from the electrical signal waveforms and / or extra click preparative concentration detector corresponding to the concentration of solute in the raffinate, corresponding to the concentration of solute in the extract The electrical signal waveform corresponding to 0% concentration of the solute in the raffinate matches the baseline at the beginning of the step time, and / or the concentration of the solute in the extract The electrical signal waveform corresponding to 0% matches the baseline at the end of the step time As such, simulated moving bed chromatographic separation method characterized by controlling the flow rate of the eluent flowing through the fluid circulation path to the optimum flow rate. A circulating fluid flow path that is capable of connecting a plurality of columns containing the packing material for separation endlessly and forcibly circulating the fluid in one direction inside,
A raw material solution inlet for introducing the raw material solution into the circulating fluid flow path, a raffinate discharge port for extracting a non-adsorbate-rich solution from the circulating fluid flow path, which is arranged in the following order along the flow direction of the fluid, An eluent inlet for introducing the eluent and an extract outlet for extracting a solution rich in adsorbate,
Switching means for performing switching such that the eluent inlet, extract outlet, raw material solution inlet, and raffinate outlet are intermittently moved by one column along the flow direction of the fluid,
A raffinate concentration detector which is provided at a raffinate outlet and outputs a raffinate detection signal corresponding to the concentration of solute in the raffinate, and / or an extract which is provided at the extract outlet and which corresponds to the concentration of solute in the extract An extract concentration detector that outputs a detection signal,
Based on the waveform of the raffinate detection signal output from the raffinate concentration detector and / or the waveform of the extract detection signal output from the extract concentration detector, electricity corresponding to a solute concentration of 0% in the raffinate is detected. And / or the electrical signal waveform corresponding to 0% concentration of the solute in the extract matches the baseline at the end of the step time. An arithmetic processing unit that determines an optimal flow rate of the eluent in the circulating fluid flow path;
A simulated moving bed type chromatographic separation apparatus comprising: a flow rate adjusting means for adjusting a flow rate of an eluent in a circulating fluid flow path by inputting a control signal output from the arithmetic processing unit. A circulating fluid flow path that is capable of connecting a plurality of columns containing the packing material for separation endlessly and forcibly circulating the fluid in one direction inside,
A raw material solution inlet for introducing the raw material solution into the circulating fluid flow path, a raffinate discharge port for extracting a non-adsorbate-rich solution from the circulating fluid flow path, which is arranged in the following order along the flow direction of the fluid, An eluent inlet for introducing the eluent and an extract outlet for extracting a solution rich in adsorbate,
Switching means for performing switching such that the eluent inlet, extract outlet, raw material solution inlet, and raffinate outlet are intermittently moved by one column along the flow direction of the fluid,
A raffinate concentration detector that is provided at the raffinate extraction port and outputs a raffinate detection signal corresponding to the concentration of the solute in the raffinate;
Based on the waveform of the raffinate detection signal output from the raffinate concentration detector , the circulating fluid flow is controlled so that the electrical signal waveform corresponding to the solute concentration of 0% in the raffinate matches the baseline at the beginning of the step time. An arithmetic processing unit for determining an optimal flow rate of the eluent in the path;
A circulating pump for inputting a control signal output from the arithmetic processing unit and adjusting the flow rate of the fluid flowing through the circulating fluid flow path to suction and discharge the fluid;
A simulated moving bed type chromatographic separation apparatus, comprising: a raffinate extraction amount adjusting means for inputting a control signal output from the arithmetic processing unit and adjusting an extraction amount of a raffinate extracted from a raffinate extraction outlet. . A circulating fluid flow path that is capable of connecting a plurality of columns containing the packing material for separation endlessly and forcibly circulating the fluid in one direction inside,
A raw material solution inlet for introducing the raw material solution into the circulating fluid flow path, a raffinate discharge port for extracting a non-adsorbate-rich solution from the circulating fluid flow path, which is arranged in the following order along the flow direction of the fluid, An eluent inlet for introducing the eluent and an extract outlet for extracting a solution rich in adsorbate,
Switching means for performing switching such that the eluent inlet, extract outlet, raw material solution inlet, and raffinate outlet are intermittently moved by one column along the flow direction of the fluid,
An extract concentration detector that is provided at the extract outlet and outputs an extract detection signal corresponding to the concentration of the solute in the extract,
On the basis of the waveform of the extract detection signal output from the extract concentration detector, the electrical signal waveform corresponding to the solute concentration of 0% in the extract matches the baseline at the end of the step time. A processing unit that determines an optimal flow rate of the eluent in the circulating fluid flow path,
An eluent introduction amount adjusting means for inputting a control signal output from the arithmetic processing unit and adjusting an introduction amount of the eluent introduced from the eluent introduction port,
A pseudo-moving layer, comprising: a control signal output from the arithmetic processing unit, and extract extraction amount adjusting means for adjusting an extraction amount of an extract extracted from an extract extraction outlet. Type chromatographic separation equipment. A circulating fluid flow path that is capable of connecting a plurality of columns containing the packing material for separation endlessly and forcibly circulating the fluid in one direction inside,
A raw material solution inlet for introducing the raw material solution into the circulating fluid flow path, a raffinate discharge port for extracting a non-adsorbate-rich solution from the circulating fluid flow path, which is arranged in the following order along the flow direction of the fluid, An eluent inlet for introducing the eluent and an extract outlet for extracting a solution rich in adsorbate,
Switching means for performing switching such that the eluent inlet, extract outlet, raw material solution inlet, and raffinate outlet are intermittently moved by one column along the flow direction of the fluid,
A raffinate concentration detector that is provided at the raffinate extraction port and outputs a raffinate detection signal corresponding to the concentration of the solute in the raffinate;
An extract concentration detector that is provided at the extract outlet and outputs an extract detection signal corresponding to the concentration of the solute in the extract,
Based on the raffinate detection signal output from the raffinate concentration detector and the waveform of the extract detection signal output from the extract concentration detector, an electric signal waveform corresponding to a solute concentration of 0% in the raffinate is obtained. In the circulating fluid flow path , match the baseline at the beginning of the step time and the electrical signal waveform corresponding to the 0% concentration of solute in the extract matches the baseline at the end of the step time. A processing unit for determining an optimal flow rate of the eluent at
A circulating pump for inputting a control signal output from the arithmetic processing unit and adjusting the flow rate of the fluid flowing through the circulating fluid flow path to suction and discharge the fluid;
A raffinate extraction amount adjusting means for inputting a control signal output from the arithmetic processing unit and adjusting the extraction amount of the raffinate extracted from the raffinate extraction outlet,
An eluent introduction amount adjusting means for receiving a control signal output from the arithmetic processing unit and adjusting an introduction amount of an eluent introduced from an eluent introduction port,
A pseudo-moving layer, comprising: a control signal output from the arithmetic processing unit, and extract extraction amount adjusting means for adjusting an extraction amount of an extract extracted from an extract extraction outlet. Type chromatographic separation equipment.

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