CN2484564Y - Chromatographic apparatus of analog moving bed with open loop structure - Google Patents

Abstract

A simulated moving bed chromatographic device with an open-loop structure, which consists of multiple identical chromatographic columns filled with adsorbents connected in series to form an open-loop structure with a head end and a tail end that move regularly. When the eluent and sample liquid are input, the pressure distribution decreases monotonically from the beginning to the end of the open loop. The pipeline of the device is equipped with components such as filters, check valves, pressure monitoring, and constant temperature maintenance, and the output pipeline is equipped with instruments for detecting the concentration and purity of the outlet solution for control. It is especially suitable for the field where the chromatographic filler is a fine-grained chiral stationary phase and the enantioselective separation is carried out under a relatively high working pressure, especially the separation of the racemate.

Description

Simulated Moving Bed Chromatography Device with Open-loop Structure

The utility model relates to a separation device which contains an adsorbent to process liquid.

The simulated moving bed chromatography device, which has the advantages of high productivity, low eluent consumption, and convenience for automatic continuous production, is a new technology in modern chemical separation technology. It was invented and successfully developed by UOP Company of the United States (US2985589), called Sorbex technology. Large-scale industrial devices with an annual output of 10,000 tons or 1,000 tons have been successfully applied in petroleum processing, food industry and other fields.

The existing simulated moving bed chromatographic device divides the vertical fixed bed adsorption tower into uniform multiple tower sections or connects multiple identical chromatographic columns filled with adsorbent in series, and forms a headless column through a fluid circulation pump. closed-loop structure at the end and end. Each tower section or each chromatographic column is equipped with a material inlet and outlet, and moves forward a tower section or a chromatographic column along the flow direction of the mobile phase through the rotation of the rotary valve or the switching of the valve according to a certain time interval. The position of the inlet and outlet of the material can be changed by using the column, so as to simulate the countercurrent movement between the stationary phase and the mobile phase. Through the selective adsorption and separation of the adsorbent, the strong adsorption component (including one or several components) can be separated from the Continuous separation of weakly adsorbed components (may include one or several components), so it is especially suitable for separating binary mixtures that are difficult to separate by conventional separation methods. The basic characteristics of the simulated countercurrent operation of simulated moving bed chromatography, on the one hand, maintains the advantages of fixed bed batch preparation chromatography, the equipment is simple, and avoids the difficulty of realizing the real countercurrent of packing; on the other hand, it reflects the advantages of countercurrent, which can increase The driving force of mass transfer between liquid and solid can make full use of the filler, thereby fundamentally improving the separation efficiency of chromatography.

The disadvantage of the simulated moving bed chromatography device with closed-loop structure is that it generally needs to be equipped with at least three pumps, including the pump for inputting fresh eluent to the device and the pump for inputting sample liquid to the device. In addition, a circulation pump must be equipped, and the circulation pump is fixed. On the pipeline connecting the bottom and the top of the tower or fixed on a specific pipeline connecting two adjacent chromatographic columns, the working pressure, working flow rate and the composition of the delivered solution of the circulating pump all change with the movement of the inlet and outlet positions of the materials. The change of pressure distribution inside the device is also very complicated. The working pressure, working flow, working medium and pressure distribution inside the device of the above-mentioned circulating pump are constantly changing, which has little effect on devices with low working pressure, and the equipment implementation is relatively simple. The existing large-scale industrial devices with an annual output of 10,000 tons or 1,000 tons often adopt a closed-loop structure because of the use of coarse-grained zeolite molecular sieves or ion exchange resins, and the system has low working pressure.

When the simulated moving bed chromatographic device is reduced to an annual production scale of tons and applied to the enantioselective separation of high value-added products, especially the field of various racemate resolution, due to the close physical and chemical properties of enantiomers , the selectivity difference of adsorption on chiral selective packing is not big, in order to achieve high efficiency of separation, it is generally necessary to use fine particle packing, or even finer HPLC packing, so the working pressure of the system is often higher . In the above-mentioned high-pressure chromatographic separation system, the closed-loop structure in which the working pressure, flow rate, working medium, and pressure distribution inside the device of the circulating pump are constantly changing will impose strict requirements on the realization of the device, especially the circulating pump, which increases the With the difficulty of operation and the complexity of operation control, the shortcomings of the closed-loop structure become very serious.

The purpose of this utility model is to connect a plurality of identical chromatographic columns filled with adsorbents in series to form a simulated moving bed chromatographic device with an open-loop structure with a head end and a tail end that move regularly. Stationary phases and enantioselective separations at higher operating pressures, especially in the field of racemate resolution.

In order to achieve the above object, the technical scheme that the utility model adopts is as follows:

1) The inlet ends of the 1st, 2nd, 3rd, and 4th chromatographic columns filled with adsorbents are respectively connected with the 1st, 5th on-off valves, the 2nd, 6th on-off valves, the 3rd, 7th on-off valves, 4th and 8th on-off valves;

2) After the other ends of the switch valves 1, 2, 3, and 4 are connected, they are connected to the sample liquid pump through the inlet pipeline of the sample liquid; after the other ends of the switch valves 5, 6, 7, and 8 are connected, The eluent inlet pipeline is connected to the eluent pump;

3) The outlets of the 1st, 2nd, 3rd, and 4th chromatographic columns are respectively connected with the 9th, 13th, 17th, and 18th on-off valves connected at one end, the 10th, 14th, 19th, and 20th on-off valves, and the 11th, 15th, and 20th on-off valves. 21, 22 switch valves, 12, 16, 23, 24 switch valves;

4) The other ends of the 9th, 10th, 11th, and 12th on-off valves are connected to the extraction liquid outlet pipeline; the other ends of the 13th, 14th, 15th, and 16th on-off valves are connected to the residual liquid outlet pipeline; the 17th , 19, 21, 23 The other end of the on-off valve is connected and then connected to the eluent outlet pipeline;

5) The other ends of the 18th, 20th, 22nd, and 24th on-off valves are respectively connected to the inlet ports of the 2nd, 3rd, 4th, and 1st chromatographic columns through the 1st, 2nd, 3rd, and 4th check valves.

The utility model has the advantages that: it consists of multiple identical chromatographic columns filled with adsorbents connected in series to form an open-loop structure with a head end and a tail end that move regularly, and only two pumps are equipped with stable working pressure and working flow 1. The working medium inputs the eluent and the sample liquid into the device respectively, and the pressure distribution inside the device monotonically decreases from the head end to the tail end of the open-loop structure. Equipped with filters, check valves, pressure monitoring, constant temperature maintenance and other components on the input pipeline and chromatographic column connection pipeline of the device, and equipped with online detection outlet solution concentration and Purity instrumentation and control of product quality and operating parameters. The device has simple equipment, low cost, convenient operation, stable and reliable operation performance, and a wide range of applications. It is especially suitable for chromatographic packing with fine-grained chiral stationary phase and enantioselective separation under relatively high working pressure, especially for elimination The rotator splits the field.

Below in conjunction with accompanying drawing, provide the detail of the utility model by the description to embodiment.

Description of drawings:

Fig. 1 is the structural representation of the utility model;

Fig. 2 is a process flow diagram of the utility model;

Fig. 3 is the concentration distribution spectrogram of strong adsorption component and weak adsorption component along four bands;

Fig. 4 is the variation relation with time of strongly adsorbable component concentration and weakly adsorbable component concentration in extract solution outlet solution;

Fig. 5 is the relationship between the concentration of weakly adsorbed components and the concentration of strongly adsorbed components in the residual liquid outlet solution over time.

As shown in Figure 1, an open-loop simulated moving bed chromatography setup with four bands, each with a column, consists of:

1) The inlets of the 1st, 2nd, 3rd, and 4th chromatographic columns filled with adsorbents are respectively connected with the 1st, 5th on-off valves V1, V5, the 2nd, 6th on-off valves V2, V6, the 3rd , 7 on-off valves V3, V7, 4th, 8th on-off valves V4, V8;

2) After the other ends of the switch valves V1, V2, V3, and V4 of No. 1, 2, 3, and 4 are connected, they are connected to the sample liquid pump 9 through the sample liquid inlet pipeline 14, and the inlet of the sample liquid pump 9 is connected to the inlet The sample liquid tank 7 is connected; after the other ends of the 5th, 6th, 7th, and 8th switching valves V5, V6, V7, and V8 are connected, they are connected to the eluent pump 8 through the eluent inlet pipeline 13, and the eluent pump 8 The inlet of the inlet is connected to one end of the eluent tank 6, and the other end of the eluent tank 6 is divided into two routes, one of which is connected to the fresh eluent tank 5, and the other is connected to the 25th on-off valve V25;

3) The outlets of the 1st, 2nd, 3rd, and 4th chromatographic columns are respectively connected with the 9th, 13th, 17th, 18th on-off valves V9, V13, V17, V18, and the 10th, 14th, 19th, 20th on-off valves Valves V10, V14, V19, V20, No. 11, 15, 21, 22 on-off valves V11, V15, V21, V22, No. 12, 16, 23, 24 on-off valves V12, V16, V23, V24;

4) The other ends of the 9th, 10, 11, and 12 on-off valves V9, V10, V11, and V12 are connected to the extraction liquid outlet pipeline 17; the 13th, 14, 15, and 16 on-off valves V13, V14, V15, The other end of V16 is connected to the residual liquid outlet pipeline 18; the other ends of the 17th, 19, 21, and 23 switch valves V17, V19, V21, and V23 are connected to the other end of the eluent outlet pipeline 19;

5) The other ends of switch valves V18, V20, V22 and V24 of No. 18, 20, 22 and 24 are respectively connected to No. 2, 3 and 4 check valves Z1, Z2, Z3 and Z4 respectively 4. At the inlet end of the chromatographic column, a check valve is installed on the connecting pipeline 16 of the adjacent chromatographic column, which can effectively prevent back-mixing and cross-contamination of the fluid during the forced flow process.

The simulated moving bed chromatographic device with open-loop structure also includes:

1) After the extraction liquid outlet pipeline 17 is connected with the first flow measuring instrument B1, the first flow regulating valve C1, the first ultraviolet detector D1, and the first polarimeter E1 in sequence, it is divided into two paths, and one path passes through the 27th The on-off valve V27 is connected to the extraction liquid tank 20, and the other path is connected to the extraction liquid tank 22 through the 28th on-off valve V28;

2) After the residual liquid outlet pipeline 18 is connected with the second flow measuring instrument B2, the second flow regulating valve C2, the second ultraviolet detector D2, and the second polarimeter E2 in sequence, it is divided into two paths, and one path passes through the 29th polarimeter. The on-off valve V29 is connected to the residual liquid tank 21, and the other path is connected to the recovery liquid tank 22 through the 30th on-off valve V30;

3) After the eluent outlet pipe 19 is connected with the third ultraviolet detector D3, it is divided into two paths, one path is connected to the eluent tank 6 through the 25th on-off valve V25, and the other path is connected to the eluent tank 6 through the 26th on-off valve V26. Recovery tank 22.

A filter 10 and a constant temperature tank 12 are sequentially connected to the eluent inlet pipeline 13; a filter 11 and a constant temperature tank 12 are sequentially connected to the sample liquid inlet pipeline 14; Installing a filter on the liquid inlet pipeline can effectively prevent the solid particle impurities entrained in the liquid from entering the device and clogging the chromatographic column.

The inlet ports of the 1st, 2nd, 3rd, 4th chromatographic columns are respectively connected with the 1st, 2nd, 3rd, 4th pressure sensors A1, A2, A3, A4; the 1st, 2nd, 3rd, 4th chromatographic columns are all covered with jackets 15.

The 17th and 18th on-off valves V17 and V18, the 19th and 20th on-off valves V19 and V20, the 21st and 22nd on-off valves V21 and V22, the 23rd and 24th on-off valves V23, V24 is a two-position three-way valve respectively.

Each of the four bands contains one or more chromatographic columns, and the total number of chromatographic columns in the device is between 4 and 36.

All online detection signals in the above devices include temperature, pressure, flow, ultraviolet detector detection signals, polarimeter detection signals, etc., and all control signals include control signals of flow regulating valves, on-off valves, pumps, constant temperature baths and other equipment. Connect with computer monitoring system through signal cable. The computer monitoring system mainly realizes the following functions:

1. The computer monitoring system monitors the pressure distribution inside the device online through the pressure sensors A1, A2, A3, and A4 installed at the inlet end of each chromatographic column. When the pressure distribution inside the device is abnormal, it indicates that the device has a fault such as blockage or leakage, and the monitoring system will give a pressure alarm signal. When the pressure of the device is too high, the monitoring system stops all the pumps of the device to protect the device.

2. The computer monitoring system ensures that the device works at a constant temperature at the operating temperature by monitoring the temperature of the fluid medium in the constant temperature tank 12 and the chromatographic column jacket 15 .

3. The computer monitoring system detects online the sum of the concentrations of the two enantiomers in the eluent outlet solution through the ultraviolet detector D3 connected in series with the eluent outlet pipeline 19 . Under normal operating conditions, the signal of the ultraviolet detector is flat, the 25th on-off valve V25 is opened and the 26th on-off valve V26 is closed at the same time, the eluent outlet solution is close to pure eluent, which can be supplemented with fresh eluent tank 5 The fresh eluent is mixed and supplied to the eluent pump 8 to achieve the purpose of reusing the eluent. Any significant change in the UV detector indicates that something is wrong, either from system disturbances (flow disturbances, temperature changes, etc.) or from malfunctions (column aging, etc.) or from suboptimal operating conditions. In the time needed to check and solve the problem, close the 25th on-off valve V25 and open the 26th on-off valve V26 at the same time, so that the polluted eluent flows into the recovery liquid tank 22, and all the eluent inlets are freshly eluted liquid. This safeguard prevents contamination from spreading throughout the system and is especially useful for prompt resolution of problems.

4. The computer monitoring system detects the sum of the concentrations of the two enantiomers and the difference between the concentrations of the two enantiomers online through the ultraviolet detector D1 and the polarimeter E1 connected in series on the outlet pipeline 17 of the extract, thereby calculating the extraction The concentration and purity of the highly adsorbed enantiomer of the target product in the solution. Under normal operating conditions, open the 27th on-off valve V27 and close the 28th on-off valve V28 at the same time, and the qualified product will flow into the extraction liquid tank 20. When the purity of the strongly adsorbed enantiomer of the target product is lower than the target, close the 27th on-off valve V27 and open the 28th on-off valve V28 at the same time, and the unqualified products will flow into the recovery liquid tank 22, thereby ensuring that when the device is started or running When a problem occurs, the unqualified product will not contaminate the qualified product in the extraction liquid tank.

5. The computer monitoring system detects the sum of the two enantiomer concentrations and the difference between the two enantiomer concentrations online through the ultraviolet detector D2 and the polarimeter E2 connected in series on the residual liquid outlet pipeline 18, thereby calculating the residual The concentration and purity of the weakly adsorbed enantiomer of the target product in the solution. Under normal operating conditions, the 29th on-off valve V29 is opened and the 30th on-off valve V30 is closed at the same time, so that qualified products flow into the residual liquid tank 21 . When the purity of the weakly adsorbed enantiomer of the target product is lower than the target, close the 29th on-off valve V29 and open the 30th on-off valve V30 at the same time, and unqualified products will flow into the recovery liquid tank 22, thereby ensuring that when the device is started or running In the event of a problem, non-conforming product will not contaminate the acceptable product in the residual liquid tank.

6. The computer monitoring system controls the flow of materials in and out of the entire device. The monitoring system controls the inlet flow rate of the eluent and the inlet flow of the sample liquid through the eluent pump 8 and the sample liquid pump 9 respectively; through the flow measurement and control combination composed of the flow measuring instruments B1 and B2 and the flow regulating valves C1 and C2, the PID The control strategy controls the opening of the valve to adjust the outlet flow of the extraction liquid and the outlet flow of the residual liquid respectively. The Coriolis mass flowmeter is the most suitable choice for the flow measurement instruments B1 and B2. The eluent outlet flow rate is limited by the total material balance of the flow in and out of the device, and there is no need for components to control its flow rate.

7. The computer monitoring system moves all five material inlets and outlets of the device in units of one chromatographic column by implementing valve switching along the fluid flow direction at a certain time interval, so that all chromatographic columns are connected in series with a head end and a tail end. An open-loop structure for timed movement. For the simulated moving bed chromatographic device with an open-loop structure composed of four chromatographic columns as shown in Figure 1, the implementation of valve switching is to change the opening and closing of all 24 on-off valves from the first to the 24th at the same time through the computer monitoring system. and off state to achieve.

Fig. 2 is a process flow chart of the present utility model, and there are four different working states according to the sequence of implementing valve switching, namely Fig. 2 (A), Fig. 2 (B), Fig. 2 (C) and Fig. 2 (D) , are described as follows:

The working state of Fig. 2 (A) corresponds to all 24 on-off valves from the 1st to the 24th of the device in Fig. 1, only the 3rd, 5, 9, 15, 18, 20, 22, 23 on-off valves V3, V5, V9, V15, V18, V20, V22, V23 are in the open state, and the other 16 on-off valves are in the closed state. At this time, the head end of the device is the inlet end of the first chromatographic column, and the tail end of the device is the outlet end of the fourth chromatographic column. The eluent enters the device from the inlet of the first chromatographic column, and after passing through the first chromatographic column, part of the liquid is output as the extract, and the remaining liquid flows through the second chromatographic column and merges with the injection liquid, and the merged liquid flows After passing through the third chromatographic column, part of the liquid is output as residual liquid, and the remaining liquid flows out after passing through the fourth chromatographic column.

The working state of Fig. 2 (B) corresponds to all 24 on-off valves from the 1st to the 24th of the device in Fig. 1, only the 4th, 6, 10, 16, 17, 20, 22, 24 on-off valves V4, V6, V10, V16, V17, V20, V22, V24 are in the open state, and the other 16 on-off valves are in the closed state. At this time, the head end of the device is the inlet end of the second chromatographic column, and the tail end of the device is the outlet end of the first chromatographic column. The eluent enters the device from the inlet port of the second chromatographic column, and after passing through the second chromatographic column, part of the liquid is output as the extraction liquid, and the remaining liquid flows through the third chromatographic column and merges with the injection liquid, and the merged liquid flows After passing through the fourth chromatographic column, part of the liquid is output as the residual liquid, and the remaining liquid flows out after passing through the first chromatographic column.

The working state of Fig. 2 (C) corresponds to all 24 on-off valves of the device in Fig. 1 from the 1st to the 24th, only the 1st, 7th, 11th, 13th, 18th, 19th, 22nd, 24th on-off valves V1, V7, V11, V13, V18, V19, V22, V24 are in the open state, and the other 16 on-off valves are in the closed state. At this time, the head end of the device is the inlet end of the third chromatographic column, and the tail end of the device is the outlet end of the second chromatographic column. The eluent enters the device from the inlet port of the third chromatographic column, and after passing through the third chromatographic column, part of the liquid is output as the extraction liquid, and the remaining liquid flows through the fourth chromatographic column and merges with the injection liquid, and the merged liquid flows After passing through the first chromatographic column, part of the liquid is output as residual liquid, and the remaining liquid flows out after passing through the second chromatographic column.

The working state of Fig. 2 (D) corresponds to all 24 on-off valves of the device in Fig. 1 from the 1st to the 24th, only the 2nd, 8, 12, 14, 18, 20, 21, 24 on-off valves V2, V8, V12, V14, V18, V20, V21, V24 are in the open state, and the other 16 on-off valves are in the closed state. At this time, the head end of the device is the inlet end of the fourth chromatographic column, and the tail end of the device is the outlet end of the third chromatographic column. The eluent enters the device from the inlet port of the fourth chromatographic column, and after passing through the fourth chromatographic column, part of the liquid is output as the extract, and the remaining liquid flows through the first chromatographic column and merges with the injection liquid, and the merged liquid flows After passing through the second chromatographic column, part of the liquid is output as residual liquid, and the remaining liquid flows out after passing through the third chromatographic column.

When the device is in the working state of Figure 2(D), after switching the valve again, the working state of the device will return to the working state of Figure 2(A), realizing the simulation of the open-loop structure composed of four chromatographic columns A cyclic operating cycle of a moving bed chromatography unit.

As shown in Figure 2, the simulated moving bed chromatographic device with open-loop structure is divided into four zones according to the position of the material inlet and outlet. The whole device completes the separation operation process through the cooperative work of each belt:

I zone: located between the eluent inlet pipeline 13 and the extract solution outlet pipeline 17, when the adsorbent that has adsorbed the strongly adsorbed components moves from the II zone to the I zone, the strongly adsorbed components are absorbed by the eluent inlet pipe All the fresh eluent input from the pipeline 13 is desorbed, and the extract enriched in strongly adsorbable components is output from the extract outlet pipeline 17.

Zone II: Located between the extraction solution outlet pipeline 17 and the sample solution inlet pipeline 14, the adsorbent moved from the III zone is in contact with the fresh sample solution just input, and the adsorbent moves into the II zone and simultaneously adsorbs strong adsorption groups Partition weakly adsorbing components. The strongly adsorbed components enriched in the liquid flowing from zone I into zone II slowly replace the weakly adsorbed components adsorbed on the adsorbent in zone II, so that the liquid flowing from zone II into zone III contains weakly adsorbed components Adsorbents with higher concentrations and more strongly adsorbed components move into the I band.

Band III: Located between the inlet line 14 of the sample liquid and the outlet line 18 of the residual liquid, the adsorbent moved from the IV band to the III band preferentially adsorbs the strongly adsorbed components and a small amount of weakly adsorbed components in the sample liquid , the residual liquid enriched in weakly adsorbable components is output from the residual liquid outlet pipeline 18 .

IV zone: located between the residual liquid outlet pipeline 18 and the eluent outlet pipeline 19, the fully desorbed adsorbent that moves from the I zone into the IV zone and the liquid enriched in weakly adsorbed components that flows from the III zone into the IV zone contact, the weakly adsorbable components in the liquid are completely adsorbed, so that the concentration of the strong and weak components in the eluent output from the eluent outlet is close to zero, and the eluent added from the fresh eluent tank 5 After being mixed in the eluent tank 6, it is transported to belt I to realize the purpose of reusing the eluent.

Fig. 3 is the concentration distribution spectrogram of strongly adsorbing components and weakly adsorbing components along the four bands. Components gradually decrease in the direction of fluid flow in zone I, and drop to zero at the inlet end of zone I. At the same time, the strongly adsorbed components should also gradually decrease in the direction of fluid flow in zone III, and drop to zero at the outlet end of zone III. Otherwise, it will be lost with the residual liquid and reduce the product purity of weakly adsorbed components in the residual liquid. There are only weakly adsorbed components at the inlet of the IV zone, that is, at the outlet of the residual liquid, and the weakly adsorbed components gradually decline in the direction of fluid flow in the IV zone, and at the outlet of the IV zone, that is, at the outlet of the eluent, the weakly adsorbed components At the same time, the weakly adsorbed components in the II zone should also gradually decrease against the flow direction of the fluid, and drop to zero at the inlet of the II zone, otherwise they will be lost with the extract and reduce the concentration of the strongly adsorbed components in the extract. points of product purity. The band of the strongly adsorbed component extends from band III to band IV, or the band of weakly adsorbed component extends from band II to band I, which indicates that the operation of the device is poor, and the target product is strongly adsorbed or weakly adsorbed. The recovery rate and purity of the active components decrease, and in severe cases, they cannot even be separated at all.

Figure 4 is the relationship between the concentration of strongly adsorbed components and the concentration of weakly adsorbed components in the outlet solution of the extract with time. The concentration curves of the two components are cyclically changing. At the valve switching moment, the concentration of the two components increases to the maximum value instantaneously, then gradually decreases, and increases instantaneously again at the next valve switching moment. Since the concentration of strongly adsorbed components is much greater than that of weakly adsorbed components, the extract is enriched with strongly adsorbed components.

Fig. 5 is the relationship between the concentration of weakly adsorbed components and the concentration of strongly adsorbed components in the residual liquid outlet solution over time. The concentration curves of the two components are cyclically changing. At the valve switching moment, the concentration of the two components decreases to the minimum value instantaneously, then increases gradually, and decreases instantaneously at the next valve switching moment. Since the concentration of weakly adsorbed components is much greater than that of strongly adsorbed components, the residual liquid is enriched with weakly adsorbed components.

An embodiment of the present invention has been described above, but the present invention is not limited to the above-mentioned embodiment. for example:

1. The simulated moving bed chromatographic device with open-loop structure is not limited to the device composed of the above four chromatographic columns. Each of the above four bands can also contain more than one chromatographic column, and the number of chromatographic columns contained in each band can also be varied. etc., so the total number of chromatographic columns must be greater than or equal to 4, but generally speaking, the total number of chromatographic columns does not exceed 36, so the total number of chromatographic columns constituting the simulated moving bed chromatography device with open-loop structure is between 4 and 36 and does not need to be a multiple of 4 . For a simulated moving bed chromatographic device with an open-loop structure with a total number of chromatographic columns greater than 4, the connection relationship between more chromatographic columns, valves and pipelines can be expanded from Figure 1, and the working principle is the same, along the direction of fluid flow at a certain time interval All five material inlets and outlets of the device can be moved in units of one chromatographic column by implementing valve switching, and in some cases can also be moved in units of multiple chromatographic columns, but the number of chromatographic columns used as a moving unit should not exceed four bands The number of columns contained in any one band.

2. The valves used in the simulated moving bed chromatography device with open-loop structure are not limited to on-off valves. For example, the 17th and 18th on-off valves, the 19th and 20th on-off valves, the 21st and 22nd on-off valves, The 23rd and 24th on-off valves, among the above four pairs of valves, since the switching states of the two on-off valves in any pair of valves are always opposite, the above four pairs of valves are especially suitable for using four equivalent two-position three-way valves. Valve replacement; for another example, the movement of the material inlet and outlet positions can also be realized by on-off switching of on-off valves, two-position three-way valves, multi-way valves, rotary valves, or combinations of the above-mentioned valves.

3. The extraction liquid and the residual liquid are not limited to be output from the device by a flow measurement and control combination composed of a flow measuring instrument and a flow regulating valve respectively, but can also be output from the device by using a pump respectively. Of course, under the higher working pressure of the device, it is easier to adjust the flow rate by using the regulating valve than the pump, because the pump works under the unfavorable condition of back pressure at this time.

4. The eluent tank 6 can be omitted, and the outlet pipeline of the fresh eluent tank 5 can be directly connected to the outlet pipeline of the 25th on-off valve V25 and then connected to the inlet of the eluent pump 8 .

The simulated moving bed chromatographic device with an open-loop structure of the utility model is the first choice method for chromatographic separation of splitting racemic raw material medicines and producing single enantiomer medicines. This device can be used to resolve such as salbutamol, fluoxetine, ofloxacin, naproxen, ibuprofen, ketoprofen, fosfomycin, methylsulfone by selecting appropriate chiral stationary phase and eluent. Racemic raw materials such as mycin. The device can also be used for the selective separation of enantiomers in the fields of optical materials, high-grade flavors and fragrances, pesticides and insecticides. The production scale of this device is generally several tons of single enantiomer per year.

Claims (6)

1. The simulated moving bed chromatography device of open-loop structure, is characterized in that: 1) It includes four bands, each band contains at least one chromatographic column, and the inlet ports of the 1st, 2nd, 3rd, and 4th chromatographic columns [1], [2], [3], [4] filled with adsorbent are respectively There are 1st, 5th on-off valves [V1], [V5] connected at one end, 2nd, 6th on-off valves [V2], [V6], 3rd, 7th on-off valves [V3], [V7], The 4th and 8th on-off valves [V4], [V8]; 2) After the other ends of the switch valves [V1], [V2], [V3], [V4] 1, 2, 3, and 4 are connected, they are connected to the sample liquid pump [14] through the sample liquid inlet pipeline [14]. 9]; After the other ends of the 5th, 6th, 7th, and 8th on-off valves [V5], [V6], [V7], [V8] are connected, they are connected to the eluent pump through the eluent inlet pipeline [13] [8]; 3) The outlets of the 1st, 2nd, 3rd, 4th chromatographic columns [1], [2], [3], [4] are respectively connected with the 9th, 13th, 17th, 18th on-off valve [V9] connected at one end , [V13], [V17], [V18], No. 10, 14, 19, 20 on-off valves [V10], [V14], [V19], [V20], No. 11, 15, 21, 22 on-off valves Valves [V11], [V15], [V21], [V22], 12th, 16th, 23rd, 24th on-off valves [V12], [V16], [V23], [V24]; 4) The other ends of the switch valves [V9], [V10], [V11], and [V12] of No. 9, 10, 11, and 12 are connected to the extraction liquid outlet pipeline [17]; No. 13, 14, 15, and The other end of 16 on-off valves [V13], [V14], [V15], [V16] is connected to the residual liquid outlet pipeline [18]; the 17th, 19, 21, 23 on-off valves [V17], [ The other ends of V19], [V21], and [V23] are connected to each other and then connected to the eluent outlet pipeline [19]; 5) The other ends of the 18th, 20th, 22nd, 24th on-off valves [V18], [V20], [V22], [V24] respectively pass through the 1st, 2nd, 3rd, 4th check valves [Z1], [Z2 ], [Z3], [Z4] are respectively connected to the inlet ports of the 2nd, 3rd, 4th, and 1st chromatographic columns [2], [3], [4], [1]. 2. the simulated moving bed chromatography device of open-loop structure according to claim 1, is characterized in that: 1) On the extraction liquid outlet pipeline [17], the first flow measuring instrument [B1], the first flow regulating valve [C1], the first ultraviolet detector [D1], and the first polarimeter [E1] are sequentially connected. , divided into two paths, one path is connected to the extraction liquid tank [20] through the 27th on-off valve [V27], and the other path is connected to the recovery liquid tank [22] through the 28th on-off valve [V28]; 2) On the residual liquid outlet pipeline [18], the second flow measuring instrument [B2], the second flow regulating valve [C2], the second ultraviolet detector [D2], and the second polarimeter [E2] are sequentially connected Finally, it is divided into two paths, one path is connected to the residual liquid tank [21] through the 29th on-off valve [V29], and the other path is connected to the recovery liquid tank [22] through the 30th on-off valve [V30]; 3) After the eluent outlet pipeline [19] is connected with the third ultraviolet detector [D3], it is divided into two paths, one path is connected to the eluent tank [6] through the 25th on-off valve [V25], and the other is One way receives liquid recovery tank [22] through the 26th on-off valve [V26]. 3. the simulated moving bed chromatographic device of open-loop structure according to claim 1, is characterized in that: on eluent inlet pipeline [13], be connected with filter [10], constant temperature tank [12] successively; A filter [11] and a constant temperature tank [12] are connected to the sample liquid inlet pipeline [14] in sequence. 4. the simulated moving bed chromatography device of open-loop structure according to claim 1, is characterized in that: at the 1st, 2, 3, 4 chromatographic columns [1], [2], [3], [4] The inlet port is respectively connected with the 1st, 2nd, 3rd, 4th pressure sensor [A1], [A2], [A3], [A4]; the 1st, 2nd, 3rd, 4th chromatographic column [1], [2], [ 3], [4] are all wrapped with jacket [15]. 5. the simulated moving bed chromatographic device of open-loop structure according to claim 1, is characterized in that: the 17th, 18 two on-off valves [V17], [V18], the 19th, 20 two on-off valves [V17], [V18] V19], [V20], the 21st, 22 two on-off valves [V21], [V22], the 23rd, 24th two on-off valves [V23], [V24] are respectively a two-position three-way valve. 6. The simulated moving bed chromatographic device with open-loop structure according to claim 1, characterized in that: the number of chromatographic columns contained in each of the four bands is one or more, and the total number of chromatographic columns in the device is between 4 and 36. between.

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