JPH04334504A - Dummy moving bed type chromatographic separator - Google Patents

Abstract

PURPOSE:To obtain a simply controllable inexpensive structure in the whole constitution of a dummy moving bed type chromatographic separator noticing an apparatus for circulating a liquid between a large number of unit packed towars endlessly connected in series. CONSTITUTION:A large number of unit packed towers C1-C8 are endlessly connected in series and, separately from the system of the piping H of the packed towers endlessly connected in series, bypass circulating line piping I meeting with a raw liquid from the terminal of the packed tower positioned on the upstream side of an apparatus supplying the raw liquid to said system is provided and one circulating pump P12 is provided on the way thereof and, further, bypass circulating line piping J meeting with an eluate from the terminal of the packed tower provided on the upstream side of a position supplying the eluate to said system is provided and one circulating pump P11 is provided on the way thereof.

Description

[Detailed description of the invention]

0001

[Industrial Application Field] The present invention consists of a large number of packed columns connected in series and endlessly filled with an adsorbent capable of selectively adsorbing a specific component among two or more components contained in a stock solution. This invention relates to a simulated moving bed chromatographic separation device.

0002

[Prior Art] A simulated moving bed chromatographic separation device typically consists of a large number of units packed with an adsorbent that has the ability to selectively adsorb a specific component among two or more components contained in a stock solution. By connecting the columns (hereinafter simply referred to as packed columns) in series with piping, and by connecting the last packed column and the foremost packed column with piping, the entire system is formed as an endlessly connected packed column group. Supply of the stock solution using a device
By keeping the respective positional relationships of the eluent supply, raffinate solution withdrawal, and extract solution constant, and moving these positions downstream over time,
It is well known that this is a device that simulates a moving bed treatment operation without actually moving the adsorbent.

[0003] To explain the above-mentioned typical apparatus with reference to FIG. 2, C1 to C8 are packed columns filled with a predetermined adsorbent, and these are connected in an endless series by piping H. A circulation pump P1 is interposed in the piping between the column C8 and the packed column C1, and in this apparatus of this example, liquid circulation is performed by one circulation pump P1.

[0004] The piping H between each of the packed towers has raffinate liquid extraction valves A1 to A on its upstream side.
The extraction pipes a1 to a8 with 8 interposed and the extraction pipes b1 to b8 with extract liquid extraction valves B1 to B8 interposed are branched and connected. Stock solution supply piping f1 to f8 with valves F1 to F8 interposed therein, and eluent supply valves D1 to D8
Eluent supply pipes d1 to d8 are branched and connected. In addition, the above-mentioned raffinate liquid extraction piping a1~
a8 are connected to the merging pipe R, respectively, and are provided so that the liquid can be extracted via the back pressure valve V; similarly, the extract liquid extraction pipes b1 to b8 are respectively connected to the merging pipe E, and are connected to the pump P4. The liquid is drawn out at a constant flow rate through the tube. Further, each of the stock solution supply pipes f1 to f8 is connected to a distribution pipe F to which the stock solution is supplied from the pump P3, and each of the eluent solution supply pipes d1 to d8 is connected to a distribution pipe D to which the eluent is supplied from the pump P2. It is connected.

In the above configuration, the stock solution and the eluent are supplied to predetermined positions (for example, the stock solution is supplied to the top of the packed column C5, and the eluent is supplied to the top of the packed column C1), and the raffinate solution is supplied to the top of the packed column C1. By extracting the extract liquid from a predetermined position (for example, extracting the raffinate liquid from the end of the packed column C6, and extracting the extract liquid from the end of the packed column C2), the system moves from the upstream side to the downstream side. It is divided into a first compartment, a second compartment, a third compartment, and a fourth compartment in which each component is enriched (that is, the enriched region of each component is divided for the adsorbent). When such an operation is continued for a certain period of time, the first to fourth sections start from the packed column C2, so the opening and closing of each valve is switched, and the elution is carried out at the top of the packed column C2. supplying the liquid, supplying the raw liquid to the top of the packed column C6, extracting the raffinate liquid from the end of the packed column C7, and extracting the extract liquid from the end of the packed column C3,
Such an operation is repeated at the above-mentioned fixed time intervals to move the sample to the downstream side, thereby achieving the intended pseudo-moving bed type chromatographic separation.

[0006]

[Problems to be Solved by the Invention] In the simulated moving bed chromatographic separator having the above configuration, the flow rate and composition of the circulating liquid flowing through each part of the packed column group system are as follows:
They do not match in the first to fourth sections described above, and therefore, in the apparatus configuration shown in FIG. The states belonging to the first to fourth partitions are sequentially transferred. For this reason, every time the section to which the circulation pump P1 belongs changes, it is necessary to change the flow rate of the pump P1 or perform control corresponding to changes in viscosity.

[0007] For this reason, the circulation pump P1 or the flow rate control device for this pump needs to have a high-performance mechanism, which makes the device expensive. There has been a problem in that it is difficult to provide an inexpensive simulated moving bed chromatographic separation device.

From the above point of view, instead of installing a circulation pump in the piping system in which the packed tower group is connected in series, as shown in FIG. Independent circulation line piping J and circulation pump P11 in the middle
For example, instead of directly returning the liquid flowing from the top of the packed column C1 in the first section to C2...C8, to the top of the packed column C1 from the end of the packed column C8 to the top of the packed column C1. By interposing a three-way valve G8 in the middle of the pipe that returns to the pipe, the liquid flows to the circulation line pipe J side, and the liquid that has passed through the circulation line pipe J joins the eluent distribution pipe D to the packed column C1. It is conceivable to construct a device with top flow. A three-way valve G for flowing liquid into the circulation line pipe J, which is this branch pipe, is installed between each packed tower, and the flow path is switched by the three-way valve to the downstream side in accordance with the transition from the first section to the fourth section. This can be done over the entire operating range of the device.

According to such a device, the liquid from the end of the fourth section is passed through the circulation line piping J and then supplied to the top of the first section, so that the liquid is supplied to each unit packed column in the circulation system. The flow can be obtained in exactly the same way as in the configuration shown in Fig. 2, and the liquid flowing to the circulation pump P11 is always the liquid from the end of the fourth section, and the flow rate of the circulation pump P11 can be changed or the viscosity can be changed. This has the advantage that it is not necessary to carry out such control, and it can be advantageously implemented in a relatively small-sized device.

However, in this type of device, only one circulation pump can be installed in the circulation line piping J, and therefore the pump pressure required to circulate the liquid across a large number of packed towers becomes high. The pressure-resistant design of the packed tower is important, and there is a drawback that it cannot be advantageously applied as it is to large-scale simulated moving bed chromatography separation equipment, which generally requires installing many circulation pumps in the middle of endless series piping. There is still room for improvement in providing large-scale simulated moving bed chromatographic separation devices that can be implemented on a large scale.

The present inventor has conducted various studies from this point of view, and has developed a pseudo-moving bed that allows easy flow rate control of circulation pumps, etc., has fewer restrictions on pressure-resistant design of packed towers, etc., and can be constructed at low cost. The present invention was developed after extensive research with the aim of providing a type chromatographic separation device.

Another object of the present invention is to conveniently utilize the structure of a liquid supply valve branched from a distribution pipe, which is necessary for rationally configuring this type of device, to implement the present invention. The object of the present invention is to provide a pseudo moving bed chromatographic separation device that requires as few additional structures as possible and can be effectively implemented on an industrial scale.

Another object of the present invention is to provide a simulated moving bed type chromatographic separation device that can operate stably for a long period of time, and in particular can use a reciprocating piston type pump as a circulation pump, and An object of the present invention is to provide a pseudo moving bed type chromatographic separation device that can operate stably even without the need for a pump.

[0014]

[Means and effects for solving the problem] In order to achieve the above-mentioned object, the present inventor has proposed
A system of packed tower groups in which a large number of packed towers filled with adsorbents that have selective adsorption ability for specific components among the components are connected in an endless series by piping, and the liquid flow of the stock solution supplied to this system. liquid circulation means for providing a circulating flow that divides the region enriched with each component in the stock solution into first to fourth compartments from the upstream side of the system, and a first compartment among these compartments; an eluent supply means for supplying an eluent to the top of the third compartment; a stock solution supply means for supplying a stock solution to the top of the third compartment; a first liquid extraction means for withdrawing the raffinate solution from the end of the third compartment; and a second liquid extracting means for extracting the extract liquid from the end of the first compartment, and as the simulated moving bed operation is performed, the first to fourth compartments are gradually removed from the packed tower on the downstream side. In the pseudo moving bed chromatography apparatus, the liquid circulation means is controlled to shift the positions of each liquid supply and liquid withdrawal to the downstream packed column in accordance with the transition to the second compartment. and a first flow path switching means for supplying the liquid flowing out from the end of the second partition to the top of the third partition after merging the liquid flowing out from the end of the second partition with the stock solution; A circulation pump is used to shut off the connection between the fourth compartment and the first compartment, and after combining the liquid flowing out from the end of the fourth compartment with the eluent, the first
a second flow path switching means that supplies the top of the section;
The simulated moving bed chromatographic separation apparatus of the present invention, which is characterized by comprising a circulation pump, has been completed.

[0015] In the above configuration, the first flow path switching means and the second flow path switching means can each be constructed using a three-way valve. It is also preferable to configure the system by a combination of one on-off valve provided in the system and on-off valves provided in two pipes branched from the system. The former has the advantage that flow path switching can be performed using only two three-way valves, but the latter has the advantage that the entire configuration can be constructed at low cost considering the structure of the valve device.

It goes without saying that the present invention can be applied to the typical conventional apparatus for performing pseudo-moving bed operation as explained in FIG. It can also be applied to other types of equipment unless otherwise specified. For example, the first flow path switching means and the second flow path switching means may be connected to a first liquid extraction means that is provided branching from the piping of the system in order to extract the liquid from the end of each packed column. A pseudo moving bed device characterized by being provided downstream of the branching position of the second liquid extraction means to perform the so-called three-zone system operation already proposed by the present applicant (
Patent Application No. 60-228806 (Japanese Patent Application No. 62-91205
(No.)) can also be applied.

[0017] The first circulation pump in the above configuration may be provided after or before the position where the eluent is supplied to the circulation line piping J; It has the advantage of being able to use a smaller pump. Similarly, the second circulation pump may be provided after or before the position where the stock solution is supplied to the pipe I.

[0018] Note that in order to focus on and further emphasize the effect of having a plurality of circulation line pipes according to the present invention, the liquid from the end of the first compartment is diverted to the top of the second compartment. A configuration in which an introduction route is provided and a circulation pump is installed in the middle of the route, or a route is provided to introduce the liquid from the end of the third compartment to the top of the fourth compartment and a circulation pump is installed in the middle of the route. Although it is conceivable, in the case of realizing an actual industrial-scale pseudo moving bed chromatographic separation apparatus, the structure of the present invention can sufficiently obtain excellent effects that have not been seen before.

[0019]

According to the device of the present invention, the first circulation pump only needs to be one that allows the liquid that has flowed through the first and second sections to flow to the top of the third section; is the third
Since it is sufficient that the liquid flowing through the compartment and the fourth compartment flows to the top of the first compartment, even if the first to fourth compartments are sequentially transferred downstream to the packed tower by operating the pseudo moving bed. A liquid having a constant composition substantially always flows through the first and second circulation pumps at a constant flow rate, and there is an advantage that variable control of the flow rate of the pumps or the like is not necessary.

In addition, since the packed tower group system is divided into two parts and one circulation pump is provided for each, the pressure resistance in the packed towers, etc. is lower than when one circulation pump is provided for the entire system. Design requirements are significantly relaxed,
The effect is particularly great when implementing large-scale equipment on an industrial scale.

Further, according to the present invention, in addition to the above-mentioned advantages such as pressure-resistant design, the first circulation pump (same as the second circulation pump) has the advantage that the pump only controls the flow rate of the first section or before the eluent joins. If a reciprocating piston pump, which is commonly used in small preparative chromatography devices, is used as the circulation pump, for example, it is necessary to output only the flow rate obtained by subtracting the flow rate of the eluent from the flow rate of the first compartment. It is possible,
Furthermore, there is an effect that the life of the pump is extended due to the absence of flow rate fluctuations.

Furthermore, as a particularly excellent advantage of the present invention,
With the use of the first and second circulation pumps, the extraction pump or flow control valve that was conventionally used for extracting the raffinate liquid and the extract liquid is no longer necessary, and both of them require the following:
Another advantage is that a valve capable of applying back pressure, such as a simple back pressure valve, can be used.

[0023]

EXAMPLES The present invention will be explained in detail below based on Examples, but it is obvious that the present invention is not limited to these Examples.

Example (Separation of maltose and maltotriose) FIG. 1 is an explanatory diagram showing the flow of the apparatus used in this example.

Packed column C with an inner diameter of 3.7 cm and a length of 50 cm
(C1...C8) The ends of each of the eight pipes are endlessly connected to the top of the next packed column with a pipe H via an on-off valve K (K1...K8), and each on-off valve Raffinate liquid outflow valves A (A1...A8) and extract liquid outflow valves B (B1...B8) are connected to the piping H on the upstream side of K, and the downstream side of each on-off valve K ( A stock solution supply valve F (F1...F8) and an eluent supply valve D (D1...D8) are connected to the piping H (between the next packed column), and an on-off valve K and the above-mentioned Two branch pipes are connected by branching from the system in the middle of the liquid outflow valves A and B, and one of the branch pipes is connected to the circulation line pipe J with an on-off valve M (M1 to M8) interposed in the middle. The other branch pipe has an on-off valve N (
N1 to N8) are interposed and connected to the circulation line piping I. Note that the raffinate liquid was extracted through the back pressure valve V1, and the extract liquid was extracted through the back pressure valve V2.

[0026]The one circulation line pipe J is connected to the first
The other circulation line piping I was connected to the outlet of the stock solution pump P3 via a second circulation pump P12, thereby forming a device. In addition, each packed column C was filled with Na type of strongly acidic cation exchange resin Amberlite CG-6000.

The following simulated moving bed operation was carried out using the apparatus constructed as described above.

That is, in the first step, the crude maltose solution is introduced as a stock solution from the top of the packed column C5 by opening the stock solution supply valve F5, and the eluent is introduced from the top of the packed column C1 by opening the eluent supply valve D1. Introducing water as
The raffinate liquid outflow valve A6 is opened to extract the maltotriose-rich liquid (raffinate liquid) from the end of the packed column C6, and the extract liquid outflow valve B2 is opened to extract the maltotriose-rich liquid (raffinate liquid) from the end of the packed column C2. Remove the extract liquid). Furthermore, close the on-off valve K8 provided in the system piping, and close the on-off valve M of the circulation line piping J.
8 was opened, and the entire amount of liquid from the end of the packed column C8 was merged into the eluent distribution pipe D via the first circulation pump P11, and introduced into the top of the packed column C1 from the eluent supply valve D1. . Similarly, the on-off valve K4 provided in the system piping is closed, and the on-off valve N4 of the circulation line piping I is opened to allow the entire amount of liquid from the end of the packed column C4 to be transferred via the second circulation pump P12. The raw solution was introduced into the distribution pipe F of the stock solution, and introduced into the top of the packed tower C5 through the stock solution supply valve F5.

Next, a predetermined time is set after starting this first step (this is a time corresponding to the transition of the enriched region of each component to the downstream side by one packed column). ) has elapsed, as a second step, the stock solution supply valve that was open in the first step is shifted from F5 to F6, the eluent supply valve that was open is shifted from D1 to D2,
The raffinate liquid outflow valve that was open was moved from A6 to A7, the extract liquid outflow valve that was open was moved from B2 to B3, and the open/close valve K in the system was changed from K8 to K.
1 and from K4 to K5, the opening of the on-off valve of the circulation line piping J was shifted from M8 to M1, and the opening of the circulation line piping I was shifted from the on-off valve from N4 to N1. By opening and closing these valves, the liquid flow is shifted downstream by one packed tower while maintaining the overall mutual positional relationship.

[0030] In the same manner, the operation of sequentially shifting the opening valves along the downstream side in the flow direction of the liquid is performed up to the eighth packed tower C8, and this is considered as one cycle, and the same operation is repeated thereafter. I did this. In addition, the flow rate of the first circulation pump P11 is the flow rate obtained by subtracting the flow rate of the eluent from the flow rate of the first section in all processes, and the flow rate of the second circulation pump P1
These pumps were operated at a constant flow rate, with the flow rate of No. 2 being the flow rate obtained by subtracting the flow rate of the stock solution from the flow rate of the third section in all processes.

The composition of the stock solution and the operating conditions are shown below.

Stock solution Solid concentration 49.5% Composition Maltotetraose 6.0%
Maltotriose 12.
4% maltose
76.9% glucose
4.7% movement period
6.25min/process eluent supply amount
8.48ml/min stock solution supply amount
2.12ml/min Extract liquid flow rate (calculated value) 4.95ml/min
Raffinate liquid flow rate (calculated value) 5.65ml/m
in 1st circulation pump flow rate 31.6
ml/min second circulation pump flow rate
35.1 ml/min (However, the raffinate liquid outflow rate is the sum of the flow rate of the second circulation pump P12 and the feed rate of the stock solution, minus the flow rate of the first circulation pump P11, and the extra The flow rate of the effluent is the sum of the flow rate of the first circulation pump P11 and the feed rate of the eluent, minus the flow rate of the second circulation pump P12.) One cycle of opening and closing of the valve, that is, the first step The composition of the effluent was investigated after several dozen cycles, with steps from 1 to 8 being one cycle, as shown in Table 1 below, and the results were stable, and the flow rates of the first and second circulation pumps were was substantially constant, confirming the excellent effect of the device of the present invention.

[0033]

[Table 1]

Comparative Example 1 (Separation of Maltose and Maltotriose) A comparative test was conducted using the apparatus shown in FIG. 2 above.

[0035] That is, the inner diameter is 3.7 cm and the length is 50 cm.
The terminals of each of the eight packed columns C (C1...C8) are connected endlessly to the top of the next packed column with piping H, and without providing the circulation line piping J and I in Example 1, this The apparatus was constructed in the same manner as in Example 1, except that a circulation pump P1 was interposed between the packed columns C8 and C1 of the piping.

Then, as a first step, the stock solution supply valve F
5 to open the crude maltose solution as a stock solution from the top of the packed column C5, open the eluent supply valve D1 to introduce water as an eluent from the top of the packed column C1, and open the raffinate liquid outflow valve A6 to introduce the crude maltose solution from the top of the packed column C6. A liquid containing a large amount of maltotriose (raffinate liquid) is extracted from the bottom, an extract liquid outflow valve B2 is opened, a liquid containing a large amount of maltose (extract liquid) is extracted from the bottom of the packed column C2, and then a liquid containing a large amount of maltose (extract liquid) is extracted from the bottom of the packed column C8. The liquid was introduced into the top of the packed column C1 via the circulation pump P1, and this operation was moved to the downstream side every time a predetermined time elapsed.

The flow rate of the circulation pump P1 was variably controlled as follows according to the region to which it belonged.

1st and 2nd steps: 3rd flow rate in 4th section
, 4 steps 3rd section flow rate 5th and 6th steps 2nd section flow rate 7th and 8th steps 1st section flow rate The composition of the stock solution and the operating conditions are described below.

Stock solution Solid concentration 49.4% Composition Maltotetraose 5.8%
Maltotriose 12.
5% maltose
77.2% glucose
4.5% movement period
6.25min/process eluent supply amount
8.48ml/min stock solution supply amount
2.12ml/min Extract liquid flow rate 4.95m
l/min raffinate liquid flow rate (calculated value) 5.6
5ml/min circulation pump flow rate (setting value) 1st and 2nd process 3
1.6 ml/min 3rd and 4th steps
37.3ml/min
5th and 6th steps 35.1 m
l/min 7th and 8th steps
The composition of the effluent after several tens of cycles at 40.1 ml/min was as shown in Table 2 below and was not stable.

[0040]

[Table 2]

[Brief explanation of drawings]

FIG. 1 is an explanatory diagram showing the flow of an apparatus used in an embodiment of the present invention.

FIG. 2 is an explanatory diagram showing the flow of the apparatus used in Comparative Example 1.

FIG. 3 is an explanatory diagram showing the flow of an apparatus having a circulation line.

[Explanation of symbols]

A1-A8: Raffinate liquid outflow valve B1-B8: Extract liquid outflow valve C1-C8: Packed tower
G1~G8: Three-way valve K1~K8: Open/close valve
F1-F8: Stock solution supply valve D1-D8: Eluent supply valve M1-
M8: On-off valve N1-N8: On-off valve
P1: Circulation pump P2: Eluent supply pump
P3: Stock solution supply pump P4: Extract liquid withdrawal pump P11: First circulation pump P12: Second circulation pump H: Piping
J: Circulation line piping I: Circulation line piping

Claims (6)

[Claims] Claim 1: A group of packed unit towers in which a large number of packed unit towers filled with an adsorbent having the ability to selectively adsorb a specific component among two or more components contained in a stock solution are connected in series endlessly by piping. system, and a liquid that provides a circulating flow that divides the region enriched with each component in the stock solution into the first to fourth compartments from the upstream side of the system due to the flow of the stock solution supplied to this system. a circulating means, an eluent supply means for supplying an eluent to the top of a first of these compartments, a stock solution supply means for supplying a stock solution to the top of a third compartment, and a stock solution supplying means for supplying a stock solution to the top of a third compartment; A first liquid extracting means for extracting the raffinate liquid and a second liquid extracting means for extracting the extract liquid from the end of the first compartment are provided, and the first to fourth compartments are separated over time due to the simulated moving bed operation. In a pseudo moving bed chromatography device, the liquid circulation The means isolates between the second compartment and the third compartment, and
between the first flow path switching means and the first pump means, which supply the liquid flowing out from the end of the compartment with the stock solution to the top of the third compartment, and the fourth compartment to the first compartment; and a second section which supplies the liquid flowing out from the end of the fourth section to the top of the first section after combining it with the eluent.
1. A pseudo moving bed chromatographic separation device comprising a flow path switching means and a second pump means. 2. In claim 1, the first flow path switching means includes an on-off valve that shuts off piping between the second compartment and the third compartment, and a pipe that flows out from an end of the second compartment. A pseudo-moving bed chromatography separation device characterized by a combination of on-off valves installed in branch piping that merges a liquid with a stock solution. 3. In claim 1, the second flow path switching valve includes an on-off valve that shuts off piping between the fourth compartment and the first compartment, and a pipe that flows out from an end of the fourth compartment. A pseudo moving bed chromatographic separation device characterized by comprising a combination of on-off valves interposed in branch piping that merges a liquid with an eluent. 4. A simulated moving bed chromatographic separation apparatus comprising the first channel switching means according to claim 2 and the second channel switching means according to claim 3. 5. The simulated moving bed chromatographic separation apparatus according to claim 1, wherein the first flow path switching means and the second flow path switching means are each three-way valves. [Claim 6] In any one of claims 1 to 5,
A first flow path switching means and a second flow path switching means are provided branching from the piping of the system in order to extract the liquid from the end of each unit packed column.
A pseudo moving bed type chromatographic separation device, characterized in that it is provided downstream of a branch position of a liquid extraction means.