WO2017056547A1 - 分取精製装置 - Google Patents
分取精製装置 Download PDFInfo
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- WO2017056547A1 WO2017056547A1 PCT/JP2016/065218 JP2016065218W WO2017056547A1 WO 2017056547 A1 WO2017056547 A1 WO 2017056547A1 JP 2016065218 W JP2016065218 W JP 2016065218W WO 2017056547 A1 WO2017056547 A1 WO 2017056547A1
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/38—Flow patterns
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/10—Selective adsorption, e.g. chromatography characterised by constructional or operational features
- B01D15/14—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the introduction of the feed to the apparatus
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/10—Selective adsorption, e.g. chromatography characterised by constructional or operational features
- B01D15/16—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the conditioning of the fluid carrier
- B01D15/161—Temperature conditioning
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/10—Selective adsorption, e.g. chromatography characterised by constructional or operational features
- B01D15/16—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the conditioning of the fluid carrier
- B01D15/163—Pressure or speed conditioning
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/10—Selective adsorption, e.g. chromatography characterised by constructional or operational features
- B01D15/24—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the treatment of the fractions to be distributed
- B01D15/247—Fraction collectors
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/32—Control of physical parameters of the fluid carrier of pressure or speed
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/80—Fraction collectors
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/84—Preparation of the fraction to be distributed
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
- G01N30/08—Preparation using an enricher
- G01N2030/085—Preparation using an enricher using absorbing precolumn
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/32—Control of physical parameters of the fluid carrier of pressure or speed
- G01N2030/328—Control of physical parameters of the fluid carrier of pressure or speed valves, e.g. check valves of pumps
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/38—Flow patterns
- G01N2030/382—Flow patterns flow switching in a single column
- G01N2030/385—Flow patterns flow switching in a single column by switching valves
Definitions
- the present invention relates to a preparative purification apparatus for separating and recovering one or more components contained in a solution using a liquid chromatograph.
- a preparative purification system using a liquid chromatograph is used for the purpose of collecting samples for storing various compounds obtained by chemical synthesis as a library or for detailed analysis.
- a preparative purification system systems described in Patent Document 1 and Patent Document 2 are known.
- the target component (compound) in the sample solution is temporally separated by a liquid chromatograph to introduce each target component into a separate trap column and collect it once. To do. Thereafter, a solution containing the target component at a high concentration is collected in a container (collection vessel) by flowing a solvent (elution solvent) through each trap column and eluting the target component collected in the column. Then, the target component is recovered as a solid by evaporating and drying each solution to remove the solvent.
- a solvent elution solvent
- Evaporation / drying treatment is generally performed by a method such as heating the collected solution or vacuum centrifuging.
- a method such as heating the collected solution or vacuum centrifuging.
- such a method requires several hours to one day only for the evaporation / drying process.
- various efficiency improvements such as shortening the analysis time by increasing the speed of analytical instruments and optimizing analytical methods, etc. It has been. Since the evaporation / drying process is one of the most time-consuming processes in the entire compound search process, it is important to shorten the time required for efficiency.
- a factor that takes time for evaporation / drying treatment is that water is mixed in the solution collected in the collection container.
- an organic solvent is usually used as a solvent for eluting the target component collected in the trap column. Since the organic solvent has a lower boiling point and higher volatility than water, if the solution collected in the collection container has the target component dissolved in the organic solvent, the time required for the evaporation / drying process can be reduced. .
- the target component is generally introduced into a trap column and collected together with water or a mobile phase containing water as a main component. Therefore, when the target component is collected, the target component is trapped. A large amount of water is retained in the column. Even if the organic solvent is introduced into the trap column in this state and the target component is eluted from the trap column, it is difficult to remove only the organic solvent and the target component from the trap column. Will be mixed.
- Patent Document 3 discloses a preparative purification apparatus in which an aqueous solvent retained in a column is excluded before eluting the target component from the trap column.
- an organic solvent having a specific gravity greater than that of the aqueous solvent contained in the trap column and having a low compatibility with the aqueous solvent is used to elute the target component from the trap column (elution solvent).
- elution solvent Used as And the elution solvent is introduce
- the aqueous solvent having a specific gravity lower than that of the elution solvent is first pushed up to the elution solvent and discharged from the trap column first, and then the target component is dissolved in the elution solvent and discharged from the trap column.
- the first aqueous solvent By discarding the first aqueous solvent, a solution in which the target component is dissolved only in the organic solvent (elution solvent) can be recovered.
- the problem to be solved by the present invention is to collect a target component collected in the column by flowing a solvent having a high dissolution power through the trap column while a large amount of water remains in the trap column.
- the recovery efficiency of the target component is increased while preventing water from being mixed into the recovered solution.
- the present invention is directed to flowing a solution containing a target component and a collection solvent through a trap column to collect the target component in the trap column, and then collecting the collection solvent.
- a preparative purification apparatus for collecting a target component collected in the trap column by flowing a solvent different from the trap column a) holding means for holding the trap column so that the inlet end of the trap column is at the bottom and the outlet end is at the top; b) having compatibility with the collection solvent remaining in the trap column in a state where the target component is collected in the trap column held by the holding means, and from the collection solvent
- first solvent and the second solvent connected in a switchable manner to a second solvent source containing a second solvent having a specific gravity greater than that of the first solvent and having a boiling point lower than that of the collecting solvent.
- a liquid feed control means for connecting the liquid supply means to the second solvent source and flowing the second solvent to the trap column after flowing the first solvent through the trap column with time connection; d) channel switching means for selectively connecting the outlet end of the trap column to either the waste fluid channel or the recovery channel; e) When the solution containing the collection solvent is discharged from the outlet end of the trap column, the outlet end is connected to the waste liquid flow path, and the solution containing the second solvent from the outlet end of the trap column. Is discharged, the outlet end is connected to the recovery flow path, and the solution containing the first solvent starts to be discharged from the outlet end of the trap column until the solution containing the second solvent starts to be discharged. And a flow path control means for controlling the flow path switching means so that the connection destination of the outlet end is switched from the waste liquid flow path to the recovery flow path at a predetermined timing.
- a solution containing a target component and a collection solvent is passed through a trap column to collect the target component into the trap column, and then a solvent other than the collection solvent is passed through the trap column to pass the trap.
- a preparative purification method for recovering the target component collected in the column a) With respect to the trapping solvent remaining in the trap column in a state where the target component is collected in the trap column held so that the inlet end of the trap column is at the bottom and the outlet end is at the top.
- a first solvent having compatibility and having a boiling point lower than that of the collecting solvent is fed to the inlet end of the trap column for a predetermined time; b) Subsequently, the solvent has low compatibility with the collection solvent and high compatibility with the first solvent, and has a specific gravity greater than that of the collection solvent and the first solvent, and A second solvent having a lower boiling point than the collecting solvent is fed to the inlet end of the trap column; c) When the solution containing the collection solvent is discharged from the outlet end of the trap column, the solution is allowed to flow through the waste liquid flow path, and the solution containing the second solvent is discharged from the outlet end of the trap column. And when the solution containing the first solvent starts to be discharged from the outlet end of the trap column until the solution containing the second solvent starts to be discharged. The flow path of the solution discharged from the outlet end is switched from the waste liquid flow path to the recovery flow path.
- the collection solvent mainly refers to a mobile phase used for separating a target component from a solution containing various components in a liquid chromatograph, and after collecting the target component in a trap column, A cleaning liquid used for cleaning or cleaning the inside of the column may be included.
- the collection solvent is generally an aqueous solvent containing water alone or water as a main component.
- the first solvent is a solvent that satisfies the above-mentioned compatibility, specific gravity, and boiling point with respect to the collection solvent. For example, acetonitrile (specific gravity: 0.71, boiling point: 81.6 ° C.) or methanol (specific gravity) : 0.79, boiling point: 64.7 ° C), or an organic solvent that is a mixture thereof.
- the second solvent is a solvent that satisfies the above-mentioned compatibility, specific gravity, and boiling point with respect to the collection solvent, and includes, for example, dichloromethane (specific gravity: 1.32, boiling point: 39.6 ° C.) or the like. It is an organic solvent which is a mixed solution. This mixed solution is a mixture of, for example, methanol and dichloromethane in order to adjust the dissolution power and the solubility of the compound.
- the first solvent and the second solvent are both solvents capable of eluting the target component, but a solvent having a higher elution power is used for the second solvent than for the first solvent.
- the first solvent is fed by the liquid feeding means in a state where the target component is collected in the adsorbent in the trap column and the collection solvent is collected in the trap column.
- the first solvent is fed into the trap column from the lower end thereof.
- the collection solvent in the column is pushed up. Since the first solvent is compatible with the collection solvent, In the vicinity of the boundary of one solvent, both are dissolved.
- the “predetermined time” depends on the liquid feeding speed of the first solvent, but the amount of the first solvent is sufficient to prevent contact between the two solvents by interposing between the collecting solvent and the second solvent in the trap column. Can be introduced into the trap column. Subsequently, the second solvent is fed into the column from the lower end of the trap column by the liquid feeding means, and the collection solvent and the first solvent in the column are increased as the liquid level of the second solvent rises in the trap column. Pushed up. At this time, since the second solvent is highly compatible with the first solvent, both are dissolved in the vicinity of the boundary between the second solvent and the first solvent.
- the collection solvent is first discharged from the outlet end of the trap column. At this time, the solution discharged from the trap column is caused to flow through the waste liquid flow path, and the collection solvent is discarded.
- the first solvent is subsequently discharged from the outlet end of the trap column.
- the flow path control means controls the flow path switching means to flow the solution discharged from the trap column to the recovery flow path. Thereby, the target component contained in the first solvent is taken out from the trap column and recovered. Thereafter, the solvent discharged from the trap column is switched from the first solvent to the second solvent.
- the target component collected in the trap column is removed. It can be eluted with a second solvent having a strong elution power and recovered from the column.
- the collection solvent such as water and aqueous solvent remaining in the column is discharged prior to eluting the target component from the trap column that has collected the target component.
- the timing of starting the recovery of the solution discharged from the trap column is advanced, the recovery efficiency of the target component can be increased, and water can be prevented from being contained in the recovered solution containing the target component.
- the boiling points of the recovered first solvent and second solvent are lower than that of water, evaporation / drying treatment can be performed in a short time in the subsequent process.
- the schematic block diagram of the preparative purification apparatus by one Embodiment of this invention The figure for demonstrating the change of the solvent and target component in the eluate from a trap column.
- the schematic diagram for demonstrating the change of the solvent in a trap column. The figure which shows the elution time at the time of using acetonitrile as a 1st solvent.
- (a) is when acetonitrile is not used.
- (b) is when 1 mL of acetonitrile is used.
- (c) is when 2 mL of acetonitrile is used.
- FIG. 1 is a schematic configuration diagram of a preparative purification apparatus according to an embodiment of the present invention.
- This preparative purification apparatus is an apparatus for recovering from the trap column the target components separated by a preparative liquid chromatograph apparatus (not shown) and collected in the adsorbent packed in the trap column.
- the column rack 10 holds the trap column 20 upright with the inlet end facing downward and the outlet end facing upward.
- the trap column 20 collects target components separated in advance by a preparative liquid chromatograph (not shown).
- the collection container rack 30 accommodates a collection container 31 for collecting the target component eluted from the trap column 20.
- a recovery head 40 for sending the eluate from the trap column 20 to the recovery container 31 is provided above the column rack 10 and the recovery container rack 30.
- the recovery head 40 includes a recovery channel 42 and an eluate recovery needle 41 and a discharge nozzle 43 that are connected to both ends of the recovery channel 42 with their tips directed downward.
- the recovery flow path 42 is a discharge / recovery switch for switching whether the liquid flowing into the recovery flow path 42 from the eluate recovery needle 41 is sent to the waste liquid flow path 46 leading to the waste liquid port or to the discharge nozzle 43.
- a valve 45 (flow path switching means in the present invention) is provided.
- the collection head 40 can be moved in the vertical direction (Z-axis direction in the figure), the front-rear direction (Y-axis direction in the figure), and the left-right direction (X-axis direction in the figure) by a driving mechanism (not shown). it can.
- the low-pressure valve 72 has one port g provided at the center and five ports hl provided around the port g.
- the low-pressure valve 72 connects the port g to any one of the ports hl, and the port h. Any two adjacent ports of ⁇ l can be communicated with each other.
- the port g is connected to one end of the plunger pump 81 (liquid feeding means in the present invention), and the port h is connected to the other end of the plunger pump 81.
- the port i is connected to the solvent switching valve 78.
- Port l is connected to the inlet end of trap column 20.
- the first solvent reservoir 53 (first solvent source in the present invention) contains acetonitrile as the first solvent in the present invention
- the second solvent reservoir 56 (second solvent source in the present invention) is in the present invention.
- Dichloromethane as the second solvent is accommodated.
- the solvent switching valve 78 switches the flow path so that any of these flows into the plunger pump 81.
- the control unit 64 configured by a CPU or the like has a liquid supply control unit 64a (liquid supply control unit in the present invention) and a flow path control unit 64b (flow path control unit in the present invention), which are preset programs. Accordingly, the plunger pump 81 (flow rate or flow velocity) and the discharge / recovery switching valve 45 are respectively controlled. In addition, the control unit 64 automatically performs the preparative purification work by executing a switching operation of each valve such as the low pressure valve 72 and the solvent switching valve 78 and a control of a driving mechanism (not shown). The operation unit 65 is used to input and set conditions for preparative purification work. In addition, the connection of the control part 64 and each apparatus in a figure is shown with a broken line.
- FIG. 2 is an example of a timetable of processing for the trap column 20, the discharge / recovery switching valve 45, and the solvent switching valve 78 in the present embodiment.
- the user sets the trap column 20 on which the target component has been collected in advance to the column rack 10.
- the trap column 20 is filled with water as the collection solvent in the present invention.
- the operation unit 65 instructs the control unit 64 to start processing.
- the controller 64 drives a drive mechanism (not shown) to move the recovery head 40 and insert the eluate recovery needle 41 and the discharge nozzle 43 into the outlet end of the trap column 20 and the recovery container 31, respectively.
- the flow path control unit 64 b switches the discharge / recovery switching valve 45 so that the liquid flowing into the eluate recovery needle 41 flows through the waste liquid flow path 46.
- the control unit 64 switches the low pressure valve 72 and the solvent switching valve 78, and the liquid feeding control unit 64a drives the plunger pump 81, whereby the first solvent in the first solvent reservoir 53, here acetonitrile (in the figure). In this case, CH 3 CN) is supplied from the inlet end of the trap column 20.
- the acetonitrile liquid level gradually rises from the lower end by feeding the acetonitrile (FIG. 3 (a)).
- water in the trap column 20 is also pushed up, but since acetonitrile has compatibility with water, both of them are dissolved in the vicinity of these boundaries.
- the pushed-up water overflows from the outlet end of the trap column 20 and is discharged to the outside from the waste liquid flow path 46 through the eluate collection needle 41 and the discharge / recovery switching valve 45.
- the liquid supply control unit 64a supplies acetonitrile for a predetermined time t1, stops the liquid supply by the plunger pump 81, and switches the solvent switching valve 78 to the second solvent reservoir 56. Then, by driving the plunger pump 81 again, the second solvent (dichloromethane (denoted as DCM in the figure)) is sent to the trap column 20.
- the flow path control unit 64b is configured so that the void volume in the trap column 20, that is, the volume of water and acetonitrile accumulated in the trap column 20 just before the introduction of the second solvent (dichloromethane), Based on the flow rate of liquid delivery, the time t A from the start of dichloromethane delivery until the start of acetonitrile discharge is predicted, and it is determined whether the elapsed time from the start of delivery of dichloromethane has reached the time t A To do. Further, since the target component is eluted in acetonitrile, the target component starts to be contained in the discharged solution almost simultaneously with the start of discharge of acetonitrile from the trap column 20 (FIG. 3 (c)).
- the trap column 20 is filled with dichloromethane, and the dichloromethane is discharged from the outlet end of the trap column 20 (FIG. 3 (d)). Since the target component is also eluted in the dichloromethane, the target component can be recovered by recovering in the recovery container 31.
- the liquid feeding control unit 64a determines whether or not the elapsed time from the start of feeding the dichloromethane to the trap column 20 has reached the set time t2.
- the set time t2 is a preset value, and is the time from the start of the dichloromethane feeding until the target component is completely eluted from the trap column 20, which is clarified by experiments and calculations in this embodiment.
- the control unit 64 determines that the set time t2 has elapsed, the control unit 64 stops the plunger pump 81.
- acetonitrile and dichloromethane containing the target component can be recovered in the recovery container while discarding the water in the trap column 20 into the waste liquid flow path.
- an adsorbent composed of a porous polymer, specifically a styrene divinylbenzene polymer having a particle size of 20 to 30 ⁇ m, is packed in the trap column 20 and 100 mg of caffeine as a target component is collected in the adsorbent.
- the trap column 20 was filled with water as a collecting solvent.
- acetonitrile as the first solvent and dichloromethane as the second solvent were each fed at 0.5 mL / min, and the concentration of the target component in the solution discharged from the eluate collection needle was measured with a detector.
- FIGS. 4 (a) to 4 (c) The measurement results are shown in FIGS. 4 (a) to 4 (c).
- FIG. 4 (a) shows the measurement results of a comparative experiment eluted with dichloromethane alone
- FIGS. 4 (b) and 4 (c) show the results of elution with 1 mL of acetonitrile, 2 mL and dichloromethane, respectively.
- the horizontal axis indicates the elapsed time
- the vertical axis indicates the signal strength of the detector.
- the elution time is about 80 minutes, whereas as shown in FIG. 4 (b), 1 mL of acetonitrile is used as the first solvent. When used, the elution time was about 30 minutes. As shown in FIG. 4 (c), the elution time when 2 mL of acetonitrile was used as the first solvent was about 25 minutes, and the elution time was greatly shortened. From these measurement results, it was found that acetonitrile had an effect of promoting elution of the target component.
- Styrene divinylbenzene-based polymer swells with acetonitrile, making it easy to remove target components collected in the polymer, and elution time is shortened by flowing dichloromethane with strong dissolution power in this state I think that the.
- the recovery to the recovery container is started while the second solvent is being sent, but the recovery to the recovery container may be started while the first solvent is being sent.
- the second solvent feeding is started before the first solvent is discharged from the outlet end of the trap column. Is long or the capacity of the trap column is small, the first solvent may be discharged from the trap column while the first solvent is being fed. In such a case, even when the first solvent is being fed, the discharge / recovery switching valve is switched to recover the first solvent in the recovery container.
- the recovery of the solution into the recovery container is started after acetonitrile as the first solvent starts to be discharged from the outlet end of the trap column, but the recovery of the solution may be started after the dichloromethane starts to be discharged.
- the collection solvent and the first solvent have compatibility, they are in a dissolved state near the boundary. When the amount of the first solvent fed is small or when a large amount of the collecting solvent is dissolved in the first solvent, most of the first solvent is dissolved with the collecting solvent. In this state, when the first solvent is fed to the collection container, the collection solvent in the collected solution increases. On the other hand, since the solvent for collection and the second solvent have low compatibility, they are hardly dissolved. Therefore, when a large amount of the collection solvent is dissolved in the first solvent, it is possible to prevent the collection solvent from being included in the collected solution by collecting only the second solvent.
- the solvent near the boundary between the collection solvent (water) and the first solvent that is, the solution in which the collection solvent and the first solvent are dissolved is not recovered.
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Abstract
Description
a) 前記トラップカラムの入口端が下、出口端が上になるように前記トラップカラムを保持する保持手段と、
b) 前記保持手段に保持された前記トラップカラム中に目的成分が捕集された状態で、該トラップカラム中に残る前記捕集用溶媒に対して相溶性を有し且つ該捕集用溶媒よりも沸点が低い第1溶媒が収容された第1溶媒源、及び前記捕集用溶媒に対して相溶性が低く、前記第1溶媒に対して相溶性が高い溶媒であって該捕集用溶媒及び前記第1溶媒よりも比重が大きく且つ該捕集用溶媒よりも沸点が低い第2溶媒が収容された第2溶媒源に切り替え可能に接続された、前記第1溶媒及び前記第2溶媒のいずれかを前記トラップカラムの入口端に送給する送液手段と、
c) 前記保持手段に保持された前記トラップカラム中に目的成分が捕集され、且つ該トラップカラム中に前記捕集用溶媒が残った状態で、前記送液手段を前記第1溶媒源に所定時間接続して前記第1溶媒を前記トラップカラムに流した後、前記送液手段を前記第2溶媒源に接続して前記第2溶媒を前記トラップカラムに流す送液制御手段と、
d) 前記トラップカラムの出口端を廃液流路と回収流路のいずれかに選択的に接続する流路切替手段と、
e) 前記トラップカラムの出口端から前記捕集用溶媒を含む溶液が排出されているときは該出口端を前記廃液流路に接続し、前記トラップカラムの出口端から前記第2溶媒を含む溶液が排出されているときは該出口端を前記回収流路に接続し、前記トラップカラムの出口端から前記第1溶媒を含む溶液が排出され始めてから前記第2溶媒を含む溶液が排出され始めるまでの間の所定のタイミングで該出口端の接続先を前記廃液流路から前記回収流路に切り替えるように前記流路切替手段を制御する流路制御手段と
を有する。
目的成分と捕集用溶媒を含む溶液をトラップカラムに流して該目的成分を該トラップカラム中に捕集し、その後に前記捕集用溶媒とは別の溶媒を前記トラップカラムに流して該トラップカラム中に捕集されている目的成分を回収する分取精製方法において、
a) 前記トラップカラムの入口端が下、出口端が上になるように保持されたトラップカラム中に目的成分が捕集された状態で、該トラップカラム中に残る前記捕集用溶媒に対して相溶性を有し、且つ該捕集用溶媒よりも沸点が低い第1溶媒を前記トラップカラムの入口端に所定時間送給し、
b) 続いて、前記捕集用溶媒に対して相溶性が低く、前記第1溶媒に対して相溶性が高い溶媒であって該捕集用溶媒及び該第1溶媒よりも比重が大きく且つ該捕集用溶媒よりも沸点が低い第2溶媒を前記トラップカラムの入口端に送給し、
c) 前記トラップカラムの出口端から前記捕集用溶媒を含む溶液が排出されているときは該溶液を廃液流路に流し、前記トラップカラムの出口端から前記第2溶媒を含む溶液が排出されているときは該溶液を回収流路に流し、前記トラップカラムの出口端から前記第1溶媒を含む溶液が排出され始めてから前記第2溶媒を含む溶液が排出され始めるまでの間の所定のタイミングで該出口端から排出される溶液の流路を前記廃液流路から前記回収流路に切り替える。
スチレンジビニルベンゼン系ポリマーがアセトニトリルによって膨潤することにより、該ポリマーに捕集されていた目的成分が取れやすい状態になり、この状態で強い溶出力を有するジクロロメタンを流すことにより溶出時間が短縮されたものと思われる。
捕集用溶媒と第1溶媒は相溶性を有するため、これらの境界付近では互いに溶解した状態となる。第1溶媒の送液量が少ない場合や、第1溶媒に多量の捕集用溶媒が溶解した場合、第1溶媒のほとんどが捕集用溶媒と溶解することになる。この状態で、第1溶媒を回収容器に送液すると回収した溶液中の捕集用溶媒が多くなってしまう。一方で、捕集用溶媒と第2溶媒は相溶性が低いためこれらが溶解することはほとんどない。従って、第1溶媒に多量の捕集用溶媒が溶解している場合には、第2溶媒のみを回収することで、回収した溶液中に捕集用溶媒が含まれることを防ぐことができる。
20…トラップカラム
30…回収容器ラック
31…回収容器
40…回収ヘッド
41…溶出液回収ニードル
42…回収流路
43…吐出ノズル
45…排出/回収切替バルブ
46…廃液流路
53…第1溶媒リザーバ
56…第2溶媒リザーバ
64…制御部
64a…送液制御部
64b…流路制御部
65…操作部
72…低圧バルブ
78…溶媒切替バルブ
81…プランジャーポンプ
Claims (2)
- 目的成分と捕集用溶媒を含む溶液をトラップカラムに流して該目的成分を該トラップカラム中に捕集し、その後に前記捕集用溶媒とは別の溶媒を前記トラップカラムに流して該トラップカラム中に捕集されている目的成分を回収する分取精製装置において、
a) 前記トラップカラムの入口端が下、出口端が上になるように前記トラップカラムを保持する保持手段と、
b) 前記保持手段に保持された前記トラップカラム中に目的成分が捕集された状態で、該トラップカラム中に残る前記捕集用溶媒に対して相溶性を有し且つ該捕集用溶媒よりも沸点が低い第1溶媒が収容された第1溶媒源、及び前記捕集用溶媒に対して相溶性が低く、前記第1溶媒に対して相溶性が高い溶媒であって該捕集用溶媒及び前記第1溶媒よりも比重が大きく且つ該捕集用溶媒よりも沸点が低い第2溶媒が収容された第2溶媒源に切り替え可能に接続された、前記第1溶媒及び前記第2溶媒のいずれかを前記トラップカラムの入口端に送給する送液手段と、
c) 前記保持手段に保持された前記トラップカラム中に目的成分が捕集され、且つ該トラップカラム中に前記捕集用溶媒が残った状態で、前記送液手段を前記第1溶媒源に所定時間接続して前記第1溶媒を前記トラップカラムに流した後、前記送液手段を前記第2溶媒源に接続して前記第2溶媒を前記トラップカラムに流す送液制御手段と、
d) 前記トラップカラムの出口端を廃液流路と回収流路のいずれかに選択的に接続する流路切替手段と、
e) 前記トラップカラムの出口端から前記捕集用溶媒を含む溶液が排出されているときは該出口端を前記廃液流路に接続し、前記トラップカラムの出口端から前記第2溶媒を含む溶液が排出されているときは該出口端を前記回収流路に接続し、前記トラップカラムの出口端から前記第1溶媒を含む溶液が排出され始めてから前記第2溶媒を含む溶液が排出され始めるまでの間の所定のタイミングで該出口端の接続先を前記廃液流路から前記回収流路に切り替えるように前記流路切替手段を制御する流路制御手段と
を有することを特徴とする分取精製装置。 - 目的成分と捕集用溶媒を含む溶液をトラップカラムに流して該目的成分を該トラップカラム中に捕集し、その後に前記捕集用溶媒とは別の溶媒を前記トラップカラムに流して該トラップカラム中に捕集されている目的成分を回収する分取精製方法において、
a) 前記トラップカラムの入口端が下、出口端が上になるように保持されたトラップカラム中に目的成分が捕集された状態で、該トラップカラム中に残る前記捕集用溶媒に対して相溶性を有し、且つ該捕集用溶媒よりも沸点が低い第1溶媒を前記トラップカラムの入口端に所定時間送給し、
b) 続いて、前記捕集用溶媒に対して相溶性が低く、前記第1溶媒に対して相溶性が高い溶媒であって該捕集用溶媒及び該第1溶媒よりも比重が大きく且つ該捕集用溶媒よりも沸点が低い第2溶媒を前記トラップカラムの入口端に送給し、
c) 前記トラップカラムの出口端から前記捕集用溶媒を含む溶液が排出されているときは該溶液を廃液流路に流し、前記トラップカラムの出口端から前記第2溶媒を含む溶液が排出されているときは該溶液を回収流路に流し、前記トラップカラムの出口端から前記第1溶媒を含む溶液が排出され始めてから前記第2溶媒を含む溶液が排出され始めるまでの間の所定のタイミングで該出口端から排出される溶液の流路を前記廃液流路から前記回収流路に切り替えることを特徴とする分取精製方法。
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