KR20120009962A - Operation Method of Partial Reuse Recycling Process in Pseudo Moving Bed Adsorptive Separation System for Mixture Separation Enhancement - Google Patents

Abstract

Separation mixture inlet port, raffinate outlet port, desorbent inlet port, extract outlet port, at least three adjacent chromatographic sections connecting the two adjacent, and a valve for controlling the movement of each port for each set total switch time In the separation method of the mixture using a pseudo mobile bed adsorptive separation apparatus comprising:
Storing part or all of the product discharged from the extract discharge port in the extract temporary storage tank in the first half of the total switch time; And
Disclosed is a method of separation of a hop compound comprising at least one step selected from storing in the raffinate temporary storage tank some or all of the product exiting the raffinate outlet port later in the total switch time.

Description

Recycling Partial-Discard strategy for improving the separation efficiency in the simulated moving bed chromatography

The present invention relates to a method for separating a mixture using a pseudo mobile bed adsorptive separation device, and more specifically, to a high concentration of impurities in a concentration gradient of a product (extract and / or raffinate) obtained during the entire switch time. Some or all of the products of the section are stored in temporary storage tanks (extract temporary storage tanks and / or raffinate temporary storage tanks) and reused as mixtures to be separated at the mixture feed node.

Adsorptive separation method is a separation method that has the advantages of securing the stability of the material and high separation efficiency. Chromatography separation method is widely used as liquid phase adsorptive separation. However, the conventional batch chromatography method uses a large amount of mobile phase, that is, a solvent, which is not suitable for large-capacity separation due to the low throughput per hour. There is a problem to consume.

In order to solve this problem, a real moving bed adsorptive separation process (True Moving Bed) (TMB) has been developed that can produce a large amount of high-purity products continuously by introducing the concept of counter current flow.

In this real mobile bed adsorptive separation process (TMB), the stationary phase moves in the opposite direction to the flow of the mobile phase, causing countercurrent contact. Components that flow out and have low adsorptive power will flow out of the column along the mobile phase. Thus, even if the separation between the two materials is not large, pure material can be obtained if separation is possible only at both ends of the concentration distribution curve in the columns of the two materials.

However, the moving bed adsorptive separation process (TMB) has to increase the amount of filler compared to the conventional stationary separation process, there is a disadvantage that the steady state operation is difficult due to friction and leakage of the filler. In addition, back mixing of adsorbent particles by countercurrent flow is not only a big problem, but also a problem of low separation efficiency and productivity when using a small liquid flow rate to prevent this.

It was developed to overcome the disadvantages of the actual moving bed adsorptive separation process (TMB) is a simulated moving bed (SMB) adsorptive separation process proposed in US Patent No. 2,985,589 in 1961. The pseudo mobile bed adsorptive separation process (SMB) simulates the flow of the stationary phase through port movement between columns. 1 shows a process diagram of a conventional basic SMB. The basic SMB process consists of four zones of one or more columns and a desorbent inlet port, an extract-strong adsorbate outlet port, a feed inlet port and a raffinate-between each zone. Weak adsorbate) discharge port.

The desorbent mobile phase fluid can be injected into the desorbent inlet port between Zone IV and Zone I, and the fluid mixture to be separated into the mixture inlet port between Zone II and Zone III. The mixture injected in the SMB process passes the zone III by the movement of the mobile phase fluid, and the weak adsorbate raffinate moves to the fixed bed adsorbent at a faster rate than the strongly adsorbate extract, depending on the size of the interaction with the adsorbent. Separation takes place.

After a certain period of time, all inlet and outlet ports are moved by one column in the direction of movement of the fluid in the mobile phase, producing the effect of moving each column in the opposite direction to the direction of motion of the fluid in the phase of the fluid. The switch is called a switch, and the time interval between the switches is called a switch time (t _SW ) or a switching period.

The high-speed raffinate material passing through the adsorbent is obtained as a product at the raffinate discharge port located between zones III and IV, and the highly adsorbate extract material from zone III to zone II as the port moves. It is moved from II to Zone I, which is desorbed by the mobile phase fluid which is a desorbent in Zone I and obtained as a product at the extract discharge port between Zone I and Zone II.

As described above, the SMB adsorptive separation process simulates countercurrent movement with the mobile phase by creating a virtual fixed bed flow, thereby overcoming the realistic problem of the fixed bed flow in the actual mobile bed adsorptive separation process (TMB). Can be.

FIG. 2 shows the concentration gradients at both product ports when the cyclic steady state is reached in the general SMB adsorptive separation process shown in FIG. 1. 2 (a) and 2 (b) are graphs showing concentration gradients at an extract discharge port and a raffinate discharge port, respectively.

In the extract discharge port of FIG. In addition, in the raffinate discharge port in FIG.

As shown in FIG. 2, the operation method of discarding the products coming from the two outflow ports in the discard section by setting the section containing relatively few impurities and the section containing a large amount of impurities as the production section and the discard section. You-Sang Bae and Chang-Ha Lee, A partial-discard strategy for obtaining high purity products using simulated moving bed chromatography, the Journal of Chromatography A., 1122, 161-173 , 2006). The "partial discard" operation method can increase the purity of the general SMB adsorptive separation process, but has a disadvantage in that the yield and productivity are reduced by discarding a part of the product.

In order to make up for this drawback, studies have been conducted to reuse discarded portions of the “disposal section” as a feed target.

In 2007, the FOA9 Conference announced a re-use method for injecting the waste fraction mixture from the “swaking section” directly into the mixture feed port for each product port. Injecting a larger, discarded portion mixture directly into the inlet port has the problem that the separation efficiency is not good because it lowers the separation efficiency in the concentration profile in the column. Kyung-Min Kim, Yoon-Sang Bae, Jong-Ho Moon, Sang-Jin Lee, Chang-Ha Lee, "Improved Partial-Discard Strategy for Simulated Moving Bed Chromatography: Nonlinear Condition." FOA 9, Sicily, Italy May. 20-25, 2007.]

Later, in a 2008 paper and European Patent No. 1982752, the FF-SMB operation method was introduced to store the product from the product discharge port for a certain time and inject it into the mixture inlet port for some time during the switch time [Lard Christian Kebler, Andres Seidal-Morgestern, J. of Chromatogr. A 1207 (2008) 55]. In the FF-SMB, products in a section below a certain purity among the products obtained at each port are obtained as a non-product fraction. The non-production section mixture is fed back to the mixture inlet port for a specific time interval, wherein the time interval injected into the mixture inlet port is determined through process optimization calculations. Since the feed-back time interval calculated in the optimization calculation is a value calculated to achieve the target purity, it is difficult to design a process for obtaining a product above the target purity, and a guide for determining the feed-back time interval There is a problem that it is difficult to apply because there is no line. In addition, the FF-SMB has a problem that it is difficult to operate the SMB process because the operation change of the product discharge port and the mixture inlet port is made in a specific section in the middle of the switch time.

The present invention minimizes the loss of yield and yield when the “partial-discard” operation method is applied in the separation method of a mixture using a pseudo mobile bed (SMB) adsorptive separation device, and a part of the partial disposal mixture. Another object of the present invention is to provide a method for separating a mixture in which a product of higher purity than a partial throwing operation method can be obtained by simply and efficiently reusing all of them.

The present invention controls the movement of each port for each mixture inlet port, raffinate outlet port, desorbent inlet port, extract outlet port, at least three or more chromatographic sections connecting two adjacent ports and a set total switch time. In the separation method of the mixture using a pseudo moving bed adsorptive separation apparatus comprising a valve for

Storing part or all of the product discharged from the extract discharge port in the extract temporary storage tank in the first half of the total switch time; And

A method of separating a hop compound comprising at least one step selected from the step of storing in a raffinate temporary storage tank some or all of the product exiting the raffinate discharge port later in the total switch time.

In the method for separating a mixture according to the present invention, by storing some or all of the products from each discharge port in a temporary storage tank, the stored products can be reused in the mixture inlet port as a mixture to be reused, thereby increasing the purity of the product. have.

In the pseudo mobile bed adsorptive separation apparatus used in the mixture separation method of the present invention, the chromatography section connects two adjacent ports. The number of chromatographic sections is not particularly limited, and may be three to five.

In the present invention, when the number of chromatographic sections is four, it may have a closed loop which is a connected structure, and when the number of sections is three, it may have an open loop.

In addition, each chromatography section may comprise one or more chromatography columns, and in embodiments of the present invention may comprise two chromatography columns.

The valve used in the separation method of the mixture according to the present invention is to control the movement of the inlet port and outlet ports (mixture inlet port, raffinate outlet port, desorbent inlet port and extract outlet port) every set switch time This allows simulation of the countercurrent flow of the stationary phase to the mobile phase. In the present invention, one or a plurality of valves may be used, and the type of the valve is not particularly limited as long as it is a valve generally used in the art. For example, a rotary valve, a multidirectional valve, a multifunctional valve, and an on-off valve may be used. Valves and the like can be used.

The temporary storage tank used in the separation method of the mixture according to the present invention may store some or all of the products discharged from the product discharge port (extract discharge port and / or raffinate discharge port), and some or all of the stored products. Can be recycled to the mixture inlet port for reuse.

The temporary storage tank is composed of an extract temporary storage tank and / or raffinate temporary storage tank.

Separation method of the mixture according to the present invention comprises the steps of storing a part or all of the product discharged from the extract discharge port in the first half of the total switch time in the extract temporary storage tank; And

The latter may comprise one or more steps selected from the step of storing in the raffinate temporary storage tank some or all of the product exiting the raffinate discharge port.

In particular, in the present invention, it is preferable to use both of the above steps.

Extract temporary storage tank in the present invention can store the product discharged from the extract discharge port. In particular, as shown in Figure 2, since the extract discharge port is mixed with impurities (such as raffinate) in the first half of the switch time, the first half of the switch time is set to the extract discard time, part or all of the product of the discard time Is stored in the extract temporary storage tank. At this time, the length and the flow rate of the extract discard time is preferably adjustable.

In addition, the raffinate temporary storage tank in the present invention can store the product discharged from the raffinate discharge port. In particular, as shown in Fig. 2, since the impurities (extracts, etc.) are mixed in the latter part of the switch time in the raffinate discharge port, the latter part of the switch time is set as the raffinate waste time, and a part of the product of the waste time or Store everything in a raffinate temporary storage tank. At this time, it is preferable that the time length and flow rate of the raffinate discard time can be adjusted.

Separation method of the mixture according to the invention may comprise the step of recycling the part or all of the product discharged from the extract discharge port stored in the extract temporary storage tank to the mixture inlet port later in the switch time.

In addition, the present invention may include the step of recycling some or all of the product discharged from the raffinate discharge port stored in the raffinate temporary storage tank to the mixture inlet port in the first half of the switch time.

Therefore, the mixture inlet port may inject one or more of the crude mixture, the product stored in the extract temporary storage tank described above, and the product stored in the raffinate temporary storage tank into the SMB apparatus. The mixture inlet port may further inject mobile phase fluid as needed.

In particular, the crude mixture (crude mixture) in the mixture inlet port of the present invention is essentially injected, the product stored in the extract temporary storage tank and the product stored in the raffinate temporary storage tank can be selectively injected as needed, preferably The crude mixture, the product stored in the extract temporary storage tank and the product stored in the raffinate temporary storage tank are preferably injected.

In the present invention, the injection time of the crude mixture, the product stored in the extract temporary storage tank and the product stored in the raffinate temporary storage tank can be set differently at the switch time, thereby maximizing the purity of the product.

In the present invention, part or all of the product stored in the raffinate temporary storage tank may be recycled to the mixture inlet port by the reuse time set in the first half of the switch time, and part or all of the product stored in the extract temporary storage tank is in the second half of the switch time. It can be recycled to the mixture inlet port for the reuse time set in. The crude mixture can be injected in the middle of the switch time.

The reuse time of the products stored in each temporary tank is preferably adjustable.

As described above, the mixture separation method of the present invention stores part or all of the product discharged from the extract discharge port in the first half of the total switch time and / or the raffinate discharge port in the second half of the total switch time. Some or all of the product discharged from can be stored in the raffinate temporary storage tank.

At this time, in the present invention, the first half of the total switch time, the step of storing a part or all of the product discharged from the extract discharge port during the extract discard time set by the general formula 1 in the extract temporary storage tank; And

The second half of the total switch time may include separating the product discharged from the extract discharge port during the extract production time set by the following general formula (2).

[Formula 1]

t _{E - ini} = t _sw X DL _ext

[Formula 2]

t _{E - pro} = t _sw -t _{E - ini}

Where t _{E - ini} represents the time for storing some or all of the product discharged from the extract discharge port in the extract temporary storage tank, t _sw represents the total switch time, and DL _ext represents the extract discard time for the total switch time. And t _E-pro represents the time when the extract is separated.

That is, in the present invention, the extract discard time (time for storing some or all of the product discharged from the extract discharge port in the extract temporary storage tank) is affected by DL _ext .

Herein, the range of DL _ext is not particularly limited, and may be, for example, 0.05 to 0.4. When the said range is less than 0.05, the purity of the extract discharge | released in the latter half will fall, and when it exceeds 0.4, the isolation amount of a crude mixture will fall and productivity will fall.

In addition, the mixture separation method of the present invention comprises the steps of separating the product discharged from the raffinate discharge port during the raffinate production time is set by the general formula 3 in the first half of the total switch time; And

The second half of the total switch time may include storing the product discharged from the raffinate discharge port in the raffinate temporary storage tank during the raffinate discard time set by the following general formula (4).

[Formula 3]

T _{R - pro} = t _sw -t _{R - last}

 [Formula 4]

t _{R - last} = t _sw X DL _raf

Where t _{R - pro} represents the time when the raffinate is separated, t _sw represents the total switch time, and t _{R - last} stores some or all of the product discharged from the raffinate discharge port in the raffinate temporary storage tank. DL _raf represents the ratio of the raffinate discard time to the total switch time.

That is, in the present invention, the raffinate abandon time (time for storing some or all of the products discharged from the raffinate discharge port in the raffinate temporary storage tank) is influenced by DL _raf .

Here, the range of DL _raf is not particularly limited, and may be, for example, 0.05 to 0.4. If the said range is less than 0.05, the purity of the extract discharged to the front half will fall, and if it exceeds 0.4, the separation amount of a crude mixture will fall and productivity will fall.

In the mixture separation method of the present invention, part or all of the products discharged from the product discharge port and stored in the temporary storage tank are recycled to the mixture inlet port.

In this case, in the mixture separation method according to the present invention, the operation of the mixture inlet port is performed by introducing a mixture of some or all of the products stored in the raffinate temporary storage tank during the raffinate reuse time set in the first half of the entire switch time. Recycling to the port;

In the middle of the total switch time step of introducing the crude mixture to the mixture inlet port during the crude mixture (crude mixture) input time set by the following general formula (6); And

The second half of the total switch time may be a step of recycling part or all of the product stored in the extract temporary storage tank to the mixture inlet port during the extract reuse time set by the general formula (7).

[Formula 5]

T _{F - ini} = t _sw X RL _raf

[Formula 6]

T _{F - mid} = t _sw -T _{F - ini} -t _{F - last}

[Formula 7]

T _{F - last} = t _sw X RL _ext

Where T _{F - ini} represents the raffinate reuse time, t _sw represents the total switch time, RL _raf represents the ratio of the raffinate reuse time to the total switch time, and T _{F - mid} represents the dosing time of the crude mixture Where T _{F - last} represents the raffinate reuse time and RL _ext represents the ratio of extract reuse time to the total switch time.

That is, in the mixture inlet port, the raffinate is reused in the first half of the total switch time, the crude mixture is introduced in the middle, and the extract is reused in the second half. At this time, the raffinate reuse time is affected by RL _raf , and the extract reuse time is affected by RL _ext .

Here, the ranges of RL _raf and RL _ext are not particularly limited, and may be, for example, 0.05 to 0.45, respectively. If the range is less than 0.05, the reuse is performed only for a small time, so there is no difference in effect compared to when the mixture is separated using a conventional SMB process, and if it exceeds 0.45, the input time of the crude mixture is too short. If the concentration of the product is too high, there may be a problem in solubility or the optimum flow rate condition may fluctuate.

In the separation method of the mixture according to the present invention, the flow rate of recycling some or all of the products stored in the extract temporary storage tank to the mixture inlet port may be set by the following general formula (8).

[Formula 8]

Q _{F , F- last} = RR _ext XQ _E

Where Q _{F , F- last} represents the flow rate of the recycled water from the extract temporary storage tank to the mixture inlet port, Q _E represents the flow rate of the extract discharge port, and RR _ext represents the recycled flow rate for the flow rate of the extract discharge port. The ratio of the flow rate of the flow is shown.

Here, the range of RR _ext is not particularly limited, and may be, for example, 0.1 to 1. When the said range is less than 0.1, there exists a possibility that the reseparation efficiency of an extract may fall.

In addition, in the separation method of the mixture according to the present invention, the flow rate of recycling part or all of the products stored in the raffinate temporary storage tank to the mixture inlet port may be represented by the following general formula (9).

[Formula 9]

Q _{F , F- ini} = RR _raf XQ _{R , F- mid}

In the above formula, Q _{F , F- ini} represents the flow rate of the stream recycled from the raffinate temporary storage tank to the mixture inlet port, Q _{R , F- mid} represents the flow rate of the raffinate discharge port for T _{F - mid} time, RR _raf represents the ratio of the flow rate of the recycled flow to the flow rate of the raffinate outlet port for the T _{F - mid} time.

Here, the range of RR _raf is not particularly limited, and may be, for example, 0.1 to 1. When the said range is less than 0.1, there exists a possibility that the reseparation efficiency of a raffinate may fall.

In the present invention, the concentration of the crude mixture is not particularly limited, and may be, for example, the same as or higher than that of the general SMB process. In the present invention, in order to keep the total amount of the crude mixture injected, it may be inversely proportional to the ratio of the input time of the crude mixture to the total switch time. However, because of solubility limitations, in some cases productivity may be abandoned, and concentration may be increased only to the extent possible.

In the present invention, the type of the mixture to be separated is not particularly limited, and it is preferable to include a material that is difficult to separate (a substance having low selectivity), such as an aromatic hydrocarbon or racemic mixture, and the crude mixture may be adjusted in concentration depending on the operation method. It is preferable.

In addition, the present invention is the separation target mixture inlet port, raffinate outlet port, desorbent inlet port, extract outlet port, the two adjacent at least three connecting chromatographic intervals, and the movement of each port for each set total switch time In the method of operating a similar moving bed adsorption separation apparatus comprising a valve for controlling the

Storing some or all of the product exiting the extract outlet port in the first half of the total switch time in an extract temporary storage tank, and then recycling some or all of the stored product to the mixture inlet port later in the switch time; And

Storing some or all of the product exiting the raffinate outlet port later in the total switch time in the raffinate temporary storage tank, and then recycling some or all of the product to the mixture inlet port earlier in the switch time. A method of operating a pseudo moving bed adsorptive separation device comprising at least one step selected.

Here, storing part or all of the product discharged from the extract discharge port in the first half of the total switch time in the extract temporary storage tank, and then recycling part or all of the stored product to the mixture inlet port later in the switch time And storing part or all of the product exiting the raffinate outlet port later in the total switch time in the raffinate temporary storage tank, and then recycling part or all of the product to the mixture inlet port earlier in the switch time. Is preferably carried out together.

The mixture separation method according to the present invention stores a portion of the product produced during the entire switch time in a temporary storage tank and reuses the mixture inlet port as a mixture to be separated, thereby maximizing the purity of the product while minimizing the loss of other performance indicators. Can be.

1 is a conceptual diagram illustrating a method of operating a conventional SMB adsorptive separation apparatus.
FIG. 2 is a graph showing a concentration gradient at each port in the conventional SMB operating method shown in FIG. 1, and shows a concentration gradient (a) at the extract discharge port and a concentration gradient (b) at the raffinate discharge port, respectively.
3 is a conceptual diagram illustrating a method of operating a pseudo mobile bed (SMB) adsorptive separation apparatus according to the present invention.
4 is a conceptual diagram showing the time (a) and the flow rate (b) at the mixture inlet port, extract discharge port and raffinate discharge port during the switch time in the SMB operating method shown in FIG.
5 is a concentration gradient of the mixture to be injected into the mixture inlet port in the general SMB operation method (a) and the concentration gradient of the mixture to be injected into the mixture inlet port in the SMB operation method according to an example of the present invention (b) A graph representing.
6 is a comparison of the result of the change in the throw length of the SMB operation method (reuse part discarding process) according to the present invention with the results of the general SMB operation method and the partial discard operation method, purity, recovery, productivity (productivity) and solvent consumption (eluent consumption).
7 is a comparison of the results of the reuse time of the SMB operation method (reuse part discarding process) according to the present invention with the results of the general SMB operation method and the partial discarding operation method, purity (purity), recovery (recovery), It is a graph showing the productivity (productivity), solvent consumption (eluent consumption).
8 is a purity (purity), recovery rate compared with the results of the general SMB operation method and the partial discard operation method for the change of the flow rate of the mixture reuse extract separation object of the SMB operation method (reuse part discard process) according to the invention (recovery), productivity (productivity), solvent consumption (eluent consumption) is a graph.
9 is compared with the results of the general SMB operation method and the partial discard operation method for the change of the flow rate of the mixture to be reused separation separation of the SMB operation method (reuse part discard process) according to the invention, purity (purity), A graph showing recovery, productivity, and solvent consumption.

Hereinafter, with reference to the accompanying drawings, a method for separating a mixture using a pseudo mobile bed (SMB) adsorptive separation apparatus according to an embodiment of the present invention will be described in detail. The accompanying drawings show exemplary forms of the present invention, which are provided to explain the present invention in more detail, and the technical scope of the present invention is not limited thereto.

The separation method of the mixture using the SMB adsorption separation apparatus according to the present invention may be applied to the separation of the mixture of aromatic hydrocarbons, the separation of ethylbenzene, the separation of chiral compounds, and the like. It can be applied to the separation process of intermediate mixed racemic medicine.

3 is a conceptual diagram illustrating a method of operating a pseudo mobile bed (SMB) adsorptive separation apparatus according to the present invention.

In the SMB operating method according to FIG. 3, the SMB apparatus connects a feed inlet port, a raffinate outlet port, a desorbent inlet port, an extract outlet port, and two adjacent ports. It consists of four chromatographic sections, a valve for controlling the movement of each port, and an adsorption separation unit including temporary storage tanks (extract temporary storage tank and raffinate temporary storage tank) for temporarily storing the product discharged from the product port. .

In the present invention, the SMB adsorptive separation device may have a closed loop (four chromatographic sections) in which two adjacent ports are connected through a chromatographic section, and the SMB valve may be a type as described above. You can choose one or more of these. In addition, each chromatography section comprises two chromatographic columns.

In the method of operating the SMB adsorption separation apparatus, four zones play different roles. Zones II and III are separation zones. A, Raffinate, which is a weakly adsorbing material among the materials injected through the mixture inlet port between Zones II and III, is a raffinate discharge port along a desorbent which is a mobile phase. Extracted as a strong adsorbent material (B, extract) is adsorbed by the adsorbent, and the column is moved relative to the predetermined switch time interval, so that after a predetermined time passes to the extract discharge port.

Zones I and IV are playback areas. Raffinate (A), which has not been discharged from the raffinate discharge port and has passed over zone III, is adsorbed and the desorbent is regenerated. In section I, the extract (B) adsorbed by the desorbent and passed in section III is desorbed so that the stationary phase is regenerated.

On the other hand, as described above with reference to Figure 2, in the separation method of the mixture using a conventional pseudo mobile bed (SMB) adsorptive separation device, when looking at the concentration gradient (raff 2) in the (raffinate) discharge port (Fig. 2 (b)) Much of the material being an impurity, or extract, is present at the end of the switch time. In addition, in the concentration gradient of the extract discharge port (Fig. 2 (b)), most of the impurities in the raffinate (raffinate) are present in the first half of the switch time.

The product obtained at the raffinate outlet port is greatly influenced by the crude mixture entering the first half in the switch time, which means that the mixture entering the first half will be switched once the pseudo mobile bed (SMB) adsorptive separation device. This is because they can move to the raffinate outlet port together with the mobile phase fluid for a longer time until this time.

On the contrary, the product obtained at the extract discharge port is highly influenced by the mixture introduced into the latter part at the switch time, which is introduced into the latter part after the injection into the pseudo mobile bed adsorptive separation device. This is because the movement of the port, i.e. the switch, does not move with the desorbent in the direction of the raffinate outlet port, but rather to zone II.

In the method for separating a mixture using a pseudo mobile bed (SMB) adsorptive separation apparatus according to an embodiment of the present invention, the apparatus includes a raffinate temporary storage tank and an extract temporary storage tank, thereby discarding during a switch time. In time it is possible to store the product discharged through the raffinate discharge port and the extract discharge port.

The temporary storage tank is connected to the mixture inlet port to temporarily store some or all of the product discharged at the time of abandonment, and to reuse some or all of the stored product at the mixture feed node.

In addition, the embodiment of the present invention includes a multi-directional valve between the temporary storage tank and the product discharge port to send the product coming out through the discharge port to the temporary storage tank during the discard time. In the SMB adsorptive separation device, two kinds of products (raffinate and extract) are obtained from the raffinate discharge port and the extract discharge port, respectively, so that the temporary storage tank and the multidirectional valve can be used one to two sets. In the embodiment of the present invention, two sets may be used. The product in the temporary storage tank reused at the mixture inlet port is called recycle-feed recycle.

SMB adsorptive separation apparatus of the present invention is one of the original original feed (feed), raffinate reuse recycle (feed), the extract recycle recycle (feed) It may include a multi-directional valve to be connected to the mixture inlet port.

Figure 4 is a conceptual diagram showing the time (a) and the flow rate (b) in the extract discharge port, the mixture inlet port and the raffinate discharge port for the entire switch time in the SMB operating method shown in FIG.

As shown in Figure 4 (a), in the separation method of the mixture using a pseudo mobile bed (SMB) adsorptive separation apparatus according to the present invention, the mixture inlet port is divided into three sections, the switch time of the extract discharge port and the raffinate discharge port Is divided into two sections.

First, in the case of the extract discharge port, since a large amount of impurities are mixed in the first half of the switch time, set t _{E - ini} of the first half as the discard time, and store the product discharged through the extract discharge port during the above time in the extract temporary storage tank. .

On the other hand, in the case of the raffinate outlet port, since most of the impurities come out in the latter part of the switch time, the t _{r - last} of the latter part is set as the discard time, and the product which is discharged through the raffinate discharge port is temporarily stored during the time. Store in a tank

For the mixture inlet port, t _{F - ini at} the beginning of the switch time While previously the second half t _R of the switch _time, and inject the crude mixture for the _mid time, second half t _F-inject product stored during the _last raffinate temporary storage tank as an object separate reuse mixture, jungbanbu include t _F of the switch _time- t _{E - ini} in the first half of the same switch time for _last While the product stored in the extract temporary storage tank is injected as a reusable mixture.

At this time, the length of t _{E - ini} is from DL _ext (ratio of extract discard time to total switch time), and the length of t _{R - last} is from DL _raf (ratio of raffinate discard time to total switch time). The length of t _{F - ini} can be determined from RL _raf (ratio of raffinate reuse time to total switch time) and the length of t _{F - last} can be determined from RL _ext (ratio of extract reuse time to total switch time).

As shown in Figure 4 (b), the flow rate of the extract discharge port in the present invention has a constant Q _E value within the switch time. Therefore, at the extract discharge port, t _{E - ini at} the flow rate of Q _E While the product is stored in the extract temporary storage tank. T _F is the product stored in the temporary storage tank extract _- when the reuse of a mixture inlet port for the _last, the flow rate from the RR _ext (flow rate ratio of the recycled flow to the flow rate of the extract discharge port) is determined Q _F, the _{last F-} It is injected at the flow rate size.

In the SMB adsorptive separation process according to the present invention, the flow rates of zones II and IV can be fixed equally. The fluid flows into zone III in combination with the flow rate injected from zone II into the mixture inlet port, so that a change in the flow rate of the mixture inlet port changes the flow rate in zone III. In the present invention, the flow rate of zone IV is the same as zone II, so that the change in flow rate of the mixture inlet port affects only the flow rate of zone III and the raffinate discharge port. Therefore, the flow rate of the raffinate discharge port is dependent on the flow rate of the mixture inlet port. As shown in Figure 4 (b) below the flow rate of the raffinate discharge port will vary depending on the section of the mixture inlet port, t _{F - mid} Since the flow rate of the mixture inlet port (Q _{F , F mid} ) at time is constant, the flow rate (Q _{R , F mid} ) of the raffinate discharge port in the same section also has a constant value. RR _raf therefore represents the ratio of the flow rate of the recycled flow to the flow rate of the raffinate outlet port for the t _{F - mid} time.

The separation method of the mixture using the SMB apparatus according to the present invention is different from the conventional SMB operation method in the following points.

First, there is a temporary storage tank connected to the extract outlet port and / or the raffinate outlet port. In the SMB adsorption separation apparatus according to the present invention, a temporary storage tank is connected to a port from which products are discharged so as to temporarily store a product of an abandoned section of products from each product discharge port.

Second, when the product extract and the raffinate are discharged from the extract discharge port and the raffinate discharge port, respectively, the product is stored in the temporary storage tank during the discard section. In the general SMB operation method, a part containing a large amount of impurities in the concentration gradient of the product is set as a discarding section, and during the discarding section, the mixture from the discharge port is discarded, and the mixture coming out for the rest of the time is obtained as a product. On the other hand, in the SMB operation method according to the present invention, while the portion containing a large amount of impurities in the concentration gradient of the product is set to the discard section, during the discard section, a part or all of the mixture from the product discharge port is stored in the temporary storage tank.

Third, there is a difference in the feed inflow method to be separated during the switch time. In a typical SMB operation, the feed to be separated is introduced continuously. In addition, the FF-SMB injects the mixture to be reused in an arbitrary interval so as to create the desired purity through optimization calculations. However, the SMB operating method according to the present invention is injected by the appropriate position and time within the entire switch time to increase the separation performance of the product and the crude mixture stored in the temporary storage tank. At this time, as described above, the raffinate product is influenced by the mixture injected in the front during the switch time, and the extract product is influenced by the mixture injected in the back during the switch time. Inject the product of the raffinate temporary storage tank at the front of the switch time, and the product of the extract temporary storage tank at the back of the switch time. In the middle of the switch time a crude mixture is injected. In some cases, when only one type of reused separation mixture is used, only the mobile phase fluid may be injected into the section in which the other type of reused separation mixture is introduced so that the crude mixture is located in the middle of the switch time.

Fourth, in the SMB operating method of the present invention can be injected by increasing the concentration of the crude mixture higher than the concentration of the separation target (feed) injected into the general SMB process. In the general SMB operation method, the feed mixture is continuously injected, so the crude mixture is injected in the SMB operation method according to the present invention, so that the throughput of the total mixture mixture is reduced. Therefore, a concentrated concentration of the mixture to be separated can be injected in the middle of the switch time as a crude mixture to improve productivity.

At this time, the concentration of the crude mixture is not particularly limited, for example, the ratio of the input time of the crude mixture to the total switch time (T _{F - mid} / t to maintain a constant amount of the total mixture to be injected injected) _sw ) to inversely proportional to). However, because of solubility limitations, in some cases productivity may be abandoned, and concentration may be increased only to the extent possible.

Figure 5 is a concentration gradient (a) of the mixture to be injected into the mixture inlet port in the separation method of the mixture using a conventional (general) pseudo mobile bed (SMB) adsorptive separation device (a) and the mixture inlet in the separation method of the mixture in the present invention It is a graph showing the concentration gradient (b) of the crude mixture introduced into the pot.

Referring to FIG. 5, it can be seen how the concentration gradient of the crude mixture introduced from the mixture inlet port of the present invention differs from the mixture to be separated in the general SMB adsorptive separation process. In the general pseudo mobile bed (SMB) adsorptive separation process, the mixture to be separated is injected within a single switch time, whereas in the present invention, the first half of the switch time (t _{F - ini} ) has a relatively high amount of raffinate. The mixture is injected in the latter part of the switch time (t _{F - last} ) with the extract reuse separation mixture having a relatively high amount of extract. In addition, the crude mixture is injected in the mid portion of the switch time (t _F -mid), which is inversely proportional to the ratio of the length of t _{F - mid} to the total switch time in order to maintain a constant amount of the mixture to be treated during the same time. Are injected at high concentrations.

Example  And Comparative example

In the separation method of the mixture using the SMB apparatus according to the embodiment, when a partial disposal and reuse method of the fluid mixture is used in a four-zone pseudo mobile bed adsorptive separation process having two columns per zone (reuse partial disposal) Simulation studies were conducted to confirm the improved performance of the process).

In addition, as a comparative example, the conventional pseudo-mobile bed adsorptive separation process in which the partial dumping and reuse method was not used, and the partial stripe pseudo mobile bed adsorptive separation process using the partial dumping process were used.

The mixture to be separated in Examples and Comparative Examples of the present invention used a fictitious material having a very low selectivity of 1.1. The material having low selectivity is not particularly limited, and for example, racemic mixed medicines (Tbuprofen, Thailidomide 9, Benoxaprofen, Wafarin, Pemicilamine, etc.) may be used. In the case of racemic mixed medicines, one of the isomers (R-form or S-form) has a drug effect, while the other type has high purity because the drug is not effective or has side effects such as fetal malformation and carcinogenic effects. It is necessary. In particular, since the isomers (R-form and S-form) have similar physicochemical properties such as solubility, boiling point, melting point, etc., it is difficult to separate them by general separation methods, and adsorptive separation methods are used to separate the isomers in high purity. can do.

In the present invention, using a commercial program, gPROMS Modelbuilder, a general pseudo mobile bed (SMB) adsorptive separation process simulator, partial discard process simulator, and implementation of the present invention, which can predict a product discharge port, a mixture inlet port, and a concentration gradient in a column. According to the example, the reuse part discard process simulator was created, and the separation performance of each process result was compared with four performance indicators of purity, recovery, productivity, and solvent consumption.

Two mathematical models are needed to make the simulation of these processes. One is a column model that represents the adsorption and separation behavior of each component in a single column, and the other is a node model that connects several columns to form a configuration of the pseudo mobile bed adsorptive separation process. .

In the present invention, the mathematical model equations used in the column models of Examples and Comparative Examples are transport-dispersive model equations. The model equations include differential mass balance equations, linear driving force model equations, equilibrium isotherm and initial and boundary conditions for each material. ) In addition, the node model consists of mass balance equations for the flow rate and concentration relationship at the connection of each column and port to represent the configuration of the SMB adsorptive separation apparatus.

Table 1 shows the SMB system and operating parameters for performing the general SMB process simulator using the mathematical model equations as described above.

SMB system parameters SMB configuration 2-2-2-2 (8 column) D (column diameter) (cm) 2.6 L (column length) (cm) 10.5 ε (total porosity) 0.4 N _disp (the number of dispersion units) 400 mass transfer coefficient k (both components) (1 / s) 0.5 Isotherm coefficient K _A (raffinate component) (-) 3.00 K _B (extract component) (-) 3.30 b _A (raffinate component) (L / g) 0.03 b _B (extract component) (L / g) 0.04 Operating parameters C _{i , F} (feed concentration) i = A, B (g / L) 1.0 Q _F (feed flowrate) (ml / min) 2 Q _E (extract flowrate) (ml / min) 6.542 Q _R (raffinate flowrate) (ml / min) 4 Q _D (desorbent flowrate) (ml / min) 8.542 Q ₁ (flowrate of zone1) (ml / min) 75.082 Q ₂ (flowrate of zone2) (ml / min) 68.54 Q ₃ (flowrate of zone3) (ml / min) 50.74 Q ₄ (flowrate of zone ₄ ) (ml / min) 66.54 T _sw (switching time) (ml / min) 107.34

As described above, the reuse partial discard process according to the present invention has six variables, DL _ext , DL _raf , RL _ext , RL _raf , RR _ext and RR _raf , and the partial discard process is the length of the partial discard interval of the product. And four variables _, DL _ext , DL _{raf ,} DT _ext, and DT _{raf ,} which represent locations of partial truncation intervals. Examples and Comparative Examples, the part rejected the extract discharge port of the present invention is always in the switch time the first part, Rafi part abandoned Nate discharge port is always in DT _ext variables are applied only to the second half of the switch time represents the position of the parts rejected interval , DT _raf was not considered.

In the above six variables, in order to see the results of the length of the discarding interval, the injection length and the flow rate of the mixture to be reused separation, in the embodiment, the case of DL _ext = DL _raf , RL _ext = RL _raf In order to examine the effect independently, when changing one variable, the other variables were fixed by setting an arbitrary value as a representative value. The representative value of the temporal length of each rounding interval and reuse is any intermediate value, DL _ext = DL _raf = 0.2, RL _ext = RL _raf = 0.2, and RR _raf = 0.5 and RR _ext = 0.3057 were set as representative values for the injection flow rate of the reusable mixture to be the same as the flow rate of the mixture to be separated in the general process and t _{F - mid} .

The general quasi-mobile bed (SMB) adsorptive separation process (Test Example 1), partial discard process (Test Examples 2 to 4), and reuse part discard process (Test Examples 5 to 16) are shown in Table 2 as follows. The design was compared and compared. Partial Discarding Process and Reuse In the partial discarding process, the waste section DL _{ext ,} DL _raf is 0.10 to 0.30, and the reuse length of the mixture to be separated in the partial discard process (RL _{ext ,} RL _raf ) is 0.10 to 0.40 and reused. The process was designed while the flow rate (RR _raf , RR _ext ) of the mixture to be separated varied from 0.20 to 1.

DL _ext DL _raf RL _ext RL _raf RR _ext RR _raf C _{A , F, F- mid} C _{B , F, F- mid} Test Example 1 - - - - - - 1.0 1.0 Test Example 2 0.10 0.10 - - - - 1.0 1.0 Test Example 3 0.20 0.20 - - - - 1.0 1.0 Test Example 4 0.30 0.30 - - - - 1.0 1.0 Test Example 5 0.10 0.10 0.20 0.20 0.3057 0.50 1.67 1.67 Test Example 6 0.20 0.20 0.20 0.20 0.3057 0.50 1.67 1.67 Test Example 7 0.30 0.30 0.20 0.20 0.3057 0.50 1.67 1.67 Test Example 8 0.20 0.20 0.10 0.10 0.3057 0.50 1.25 1.25 Test Example 9 0.20 0.20 0.30 0.30 0.3057 0.50 2.5 2.5 Test Example 10 0.20 0.20 0.40 0.40 0.3057 0.50 5.0 5.0 Test Example 11 0.20 0.20 0.20 0.20 0.20 0.50 1.67 1.67 Test Example 12 0.20 0.20 0.20 0.20 0.60 0.50 1.67 1.67 Test Example 13 0.20 0.20 0.20 0.20 One 0.50 1.67 1.67 Test Example 14 0.20 0.20 0.20 0.20 0.3057 0.20 1.67 1.67 Test Example 15 0.20 0.20 0.20 0.20 0.3057 0.60 1.67 1.67 Test Example 16 0.20 0.20 0.20 0.20 0.3057 One 1.67 1.67

In the present invention, Figures 6 to 9 show the results of the conventional SMB adsorptive separation method according to an embodiment of the present invention, the general SMB operation method, partial discarding process and reuse partial discarding process (SMB operating method according to the present invention). ) Is a graph comparing the results according to the present invention, and shows purity, recovery, productivity, and solvent consumption.

6 is a general SMB operation method (conventional SMB, Test Example 1), and a "partial-discard" operation method (Test Examples 2 to 4) according to the length of the rounding interval when another variable is fixed to the representative value. ) And the method of "recycling partial-discard" operation (separation method of the mixture according to the present invention, Test Examples 5 to 7). Since the reuse time and the flow rate are fixed, the length of the discard section means that a large portion of the product is discarded. As the length of the discard section is longer, the purity of the partial discard operation method and the reuse partial discard operation method is improved, while other performance indicators show worsening results. However, in the case of the reused part-off operation method, the higher purity due to reuse is achieved compared to the result of the general method or the part-off operation method, and the loss of other performance indicators is reduced compared to the part-off operation method, especially DL _ext = DL _raf = In the case of 0.10, the recovery and productivity are similar to those of the general process, and in the case of the solvent consumption, the result is improved compared to the general method.

Figure 7 shows the results according to the change of the injection time of the mixture to be reused separation (Test Example 6, Test Example 8, Test Example 9 and Test Example 10) in the reuse part discard operation method while the other variable is fixed to a representative value It is shown in comparison with the SMB operation method (Test Example 1) and the partial discard operation method (Test Example 3). The change in recycle length (RL) is a variable that controls the amount of reuse by changing the injection time of the reused mixture. The larger the RL, the longer the injection of the mixture to be reused, and the greater the effect of reuse, resulting in an increase in all performance indicators, but at a higher concentration of the original mixture to be equalized. -feed), it can be seen that the purity of raffinate is slightly decreased when RL _ext = RL _raf = 0.40 compared to RL _ext = RL _raf = 0.30.

FIG. 8 shows the result when the flow rate of the extract reused separation target mixture is changed, and FIG. 9 shows the result when the flow rate of the raffinate reuse separation target mixture is changed. As can be seen in Figure 8, increasing the flow rate of the mixture to be reused to separate the extract can be improved in the case of the extract all performance indicators, but in the case of raffinate due to the increase in the flow rate of the raffinate discharge port and the flow rate in Zone III All performance indicators show worse results. In Figure 9, when the flow rate of the raffinate reuse separation target mixture was increased, both products slightly reduced in the case of purity, but it can be seen that the improved results in the recovery, productivity, solvent consumption of the raffinate. On the other hand, in the case of the extract shows a result that is hardly affected by the flow rate of the raffinate reuse separation mixture.

Preferred embodiments of the present invention described above are disclosed for purposes of illustration, and those skilled in the art may make various modifications, changes, and additions within the spirit and scope of the present invention. Such modifications, changes and additions should be considered to be within the scope of the following claims.

Claims (16)

Mixture inlet port, raffinate outlet port, desorbent inlet port, extract outlet port, at least three chromatographic sections connecting two adjacent ports and valves for controlling the movement of each port at a set total switch time In the separation method of the mixture using a pseudo mobile bed adsorptive separation apparatus comprising:
Storing part or all of the product discharged from the extract discharge port in the extract temporary storage tank in the first half of the total switch time; And
At least one step selected from the step of storing in the raffinate temporary storage tank some or all of the product exiting the raffinate outlet port later in the total switch time.
The method of claim 1,
Recycling part or all of the product discharged from the extract discharge port and stored in the extract temporary storage tank to the mixture inlet port later in the switch time.
The method of claim 1,
Recycling part or all of the product discharged from the raffinate discharge port and stored in the raffinate temporary storage tank to the mixture inlet port in the first half of the switch time.
The method of claim 1,
The first half of the total switch time step of storing a part or all of the product discharged from the extract discharge port during the extract discard time set by the general formula 1 in the extract temporary storage tank; And
In the latter part of the total switch time, the separation method of the mixture comprising the step of separating the product discharged from the extract discharge port during the extract production time set by the following general formula (2):
[Formula 1]
t _{E - ini} = t _sw X DL _ext
[Formula 2]
t _{E - pro} = t _sw -t _{E - ini}
Where t _{E - ini} represents the time for storing some or all of the product discharged from the extract discharge port in the extract temporary storage tank, t _sw represents the total switch time, and DL _ext represents the extract discard time for the total switch time. And t _E-pro represents the time when the extract is separated.
The method of claim 4, wherein
DL _ext is 0.05 to 0.4.
The method of claim 1,
Separating the product discharged from the raffinate discharge port during the raffinate production time set by the following general formula (3) in the first half of the total switch time; And
In the latter part of the total switch time, a method of separating a mixture comprising storing, in a raffinate temporary storage tank, a part or all of the product discharged from the raffinate discharge port during the raffinate discharging time set by the following general formula (4):
[Formula 3]
T _{R - pro} = t _sw -t _{R - last}
[Formula 4]
t _{R - last} = t _sw X DL _raf
Where t _{R - pro} represents the time when the raffinate is separated, t _sw represents the total switch time, and t _{R - last} stores some or all of the product discharged from the raffinate discharge port in the raffinate temporary storage tank. DL _raf represents the ratio of the raffinate discard time to the total switch time.
The method according to claim 6,
DL _raf Is 0.05 to 0.4.
The method according to claim 2 or 3,
The first half of the total switch time includes recycling some or all of the products stored in the raffinate temporary storage tank to the mixture inlet port during the raffinate reuse time set by the following general formula (5);
In the middle of the total switch time step of introducing the crude mixture to the mixture inlet port during the crude mixture (crude mixture) input time set by the following general formula (6); And
At the end of the total switch time, a method of separating a mixture comprising recycling part or all of the product stored in the extract temporary storage tank to the mixture inlet port during the extract reuse time set by the following general formula:
[Formula 5]
T _{F - ini} = t _sw X RL _raf
[Formula 6]
T _{F - mid} = t _sw -T _{F - ini} -t _{F - last}
[Formula 7]
T _{F - last} = t _sw X RL _ext
Where T _{F - ini} represents the raffinate reuse time, t _sw represents the total switch time, RL _raf represents the ratio of the raffinate reuse time to the total switch time, and T _{F - mid} represents the input time of the crude mixture. Where T _{F - last} represents the raffinate reuse time and RL _ext represents the ratio of extract reuse time to the total switch time.
The method of claim 8,
RL _raf and RL _ext are 0.05 to 0.45, respectively.
The method of claim 8,
The flow rate of the step of recirculating part or all of the product stored in the extract temporary storage tank to the mixture inlet port is the separation method of the mixture set by the following general formula (8):
[Formula 8]
Q _{F , F- last} = RR _ext XQ _E
Where Q _{F , F- last} represents the flow rate of the recycled water from the extract temporary storage tank to the mixture inlet port, Q _E represents the flow rate of the extract discharge port, and RR _ext represents the recycled flow rate for the flow rate of the extract discharge port. The ratio of the flow rate of the flow is shown.
The method of claim 10,
RR _ext is 0.1-1.
The method of claim 8,
The flow rate of the step of recycling part or all of the product stored in the raffinate temporary storage tank to the mixture inlet port is the separation method of the mixture set by the following general formula (9):
[Formula 9]
Q _{F , F- ini} = RR _raf XQ _{R , F- mid}
In the above formula, Q _{F , F- ini} represents the flow rate of the stream recycled from the raffinate temporary storage tank to the mixture inlet port, Q _{R , F- mid} represents the flow rate of the raffinate discharge port for T _{F - mid} time, RR _raf represents the ratio of the flow rate of the recycled flow to the flow rate of the raffinate outlet port for the T _{F - mid} time.
The method of claim 12,
RR _raf is 0.1-1.
The method of claim 8,
A method of separating a mixture in which the concentration of the crude mixture is inversely proportional to the ratio (T _{F - mid} / t _sw ) of the crude mixture input time to the total switch time.
The method of claim 1,
The mixture to be separated is an aromatic hydrocarbon mixture or a racemic mixture.
Mixture inlet port, raffinate outlet port, desorbent inlet port, extract outlet port, at least three chromatographic sections connecting two adjacent ports and valves for controlling the movement of each port at a set total switch time In the method of operating a pseudo moving bed adsorptive separation apparatus comprising:
Storing some or all of the product exiting the extract outlet port in the first half of the total switch time in an extract temporary storage tank, and then recycling some or all of the stored product to the mixture inlet port later in the switch time; And
Storing some or all of the product exiting the raffinate outlet port later in the total switch time in the raffinate temporary storage tank, and then recycling some or all of the product to the mixture inlet port earlier in the switch time. A method of operating a pseudo moving bed adsorptive separation apparatus comprising at least one step selected.

Images