CN108854158B - Resin column eluent collection device - Google Patents

Resin column eluent collection device Download PDF

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Publication number
CN108854158B
CN108854158B CN201710344184.7A CN201710344184A CN108854158B CN 108854158 B CN108854158 B CN 108854158B CN 201710344184 A CN201710344184 A CN 201710344184A CN 108854158 B CN108854158 B CN 108854158B
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China
Prior art keywords
valve
eluent
buffer tank
liquid level
volume
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CN201710344184.7A
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CN108854158A (en
Inventor
余通
杨婷
肖龙重
冯芸
曹儒宾
刘荃
谢长
何水英
吴欢欢
刘迪
张东宁
刘世勇
刘哲
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Humanwell Healthcare Group Co ltd
Wuhan Kangle Pharmaceutical Co ltd
Hubei Bio-Pharmaceutical Industrial Technological Institute Inc
Original Assignee
Humanwell Healthcare Group Co ltd
Wuhan Kangle Pharmaceutical Co ltd
Hubei Bio-Pharmaceutical Industrial Technological Institute Inc
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Priority to CN201710344184.7A priority Critical patent/CN108854158B/en
Publication of CN108854158A publication Critical patent/CN108854158A/en
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D15/00Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
    • B01D15/08Selective adsorption, e.g. chromatography
    • B01D15/42Selective adsorption, e.g. chromatography characterised by the development mode, e.g. by displacement or by elution
    • B01D15/424Elution mode

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  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Treatment Of Liquids With Adsorbents In General (AREA)

Abstract

The application discloses a resin column eluent collecting device, which comprises: a resin column having a feed inlet and an eluent outlet; the pipeline is communicated with the eluent outlet, at least one part of the pipeline is a transparent pipeline and is provided with a first valve and a second valve; the first buffer tank is provided with a first eluent inlet, a first eluent outlet and a third valve, and a fourth valve is arranged at the first eluent outlet; the second buffer tank is provided with a second eluent inlet, a second eluent outlet, a fifth valve, a first liquid level sensor and a second liquid level sensor, and a sixth valve is arranged at the second eluent outlet; the liquid storage tank is provided with an eluent inlet, a vacuum extraction opening, an evacuation air port and a third liquid level sensor, a seventh valve is arranged at the evacuation air port, an eighth valve is arranged at the vacuum extraction opening, a ninth valve is arranged at the eluent inlet, and the eluent inlet is connected with a second eluent outlet; a vacuum pumping unit; and the control unit is respectively connected with the first to ninth valves and the first to third liquid level sensors.

Description

Resin column eluent collection device
Technical Field
The application belongs to the technical field of medicines, and particularly relates to a resin column eluent collecting device.
Background
In the development process of new drugs, separation and enrichment of active ingredients by using a resin column are necessary links, however, as the resin is separated and enriched by surface adsorption and internal aperture, if external force is used, the structure of the resin is destroyed, so that the effect is reduced. Therefore, the elution of the resin column is usually carried out under normal pressure, but the elution and collection are troublesome, time-consuming and labor-consuming due to the long time consumption; on the other hand, as the purposes of impurity removal, purification and separation are achieved by using the resin column, when eluent is collected, the eluent is selectively collected in sections according to the elution condition, and if the elution is stopped in the elution process, the separation, purification and enrichment of the resin column can be obviously affected.
Therefore, the existing resin column elution and collection technology needs to be further improved.
Disclosure of Invention
The present application aims to solve at least one of the technical problems in the related art to some extent. Therefore, an object of the present application is to provide a resin column eluent collecting device, by which selective collection of target collected liquid can be achieved, continuous automatic collection of eluent in a resin column can be achieved, and elution efficiency of the resin column can be improved, so as to adapt to production requirements of new drug development.
In one aspect of the application, a resin column eluate collection apparatus is provided. According to an embodiment of the application, the apparatus comprises:
the resin column is filled with resin filler and is provided with a feed inlet and an eluent outlet;
a conduit having one end in communication with the eluent outlet, at least a portion of the conduit being a transparent conduit and having a first valve and a second valve thereon;
the first buffer tank is provided with a first eluent inlet, a first eluent outlet and a third valve, a fourth valve is arranged at the first eluent outlet, and the first eluent inlet is communicated with the other end of the pipeline;
the second buffer tank is provided with a second eluent inlet, a second eluent outlet, a fifth valve, a first liquid level sensor and a second liquid level sensor, a sixth valve is arranged at the second eluent outlet, and the second eluent inlet is connected with the first eluent outlet;
the liquid storage tank is provided with an eluent inlet, a vacuum extraction opening, an air exhaust opening and a third liquid level sensor, a seventh valve is arranged at the air exhaust opening, an eighth valve is arranged at the vacuum extraction opening, a ninth valve is arranged at the eluent inlet, and the eluent inlet is connected with the second eluent outlet;
the vacuumizing unit is connected with the vacuum pumping port;
and the control unit is respectively connected with the first to ninth valves and the first to third liquid level sensors.
According to the resin column eluent collecting device provided by the embodiment of the application, the transparent pipeline is arranged on the pipeline between the eluent outlet on the resin column and the first buffer tank, whether the eluent is a target collecting liquid or not can be judged according to the color of the solution flowing through the transparent pipeline, so that the target collecting liquid can be selectively collected, meanwhile, the control unit can control the opening or closing of the valve on the first buffer tank according to the liquid level in the buffer tank, the control unit and the vacuumizing unit can judge whether the vacuum pumping is needed according to the liquid level in the second buffer tank, and therefore, the continuous automatic collection of the eluent in the resin column is realized, the labor intensity is obviously reduced, the working efficiency is improved, and the production requirements of new medicine development can be further met.
In addition, the resin column eluent collection device according to the above embodiment of the present application may have the following additional technical features:
in some embodiments of the application, the conduit comprises: the main pipeline is connected with the eluent outlet; a first branch pipe connected to the main pipe, the first valve being disposed on the first branch pipe, and the first eluent inlet being connected to the first branch pipe; and the second branch pipe is connected with the main pipeline, and the second valve is arranged on the second branch pipe. Thus, selective collection of the target collection liquid can be achieved.
In some embodiments of the application, at least a portion of the main conduit is a transparent conduit. Thereby, selective collection of the target collection liquid can be further achieved.
In some embodiments of the application, the control unit opens or closes the first and second valves based on a change in color of the solution in the transparent tubing. Thus, continuous automatic collection of the eluent in the resin column can be achieved.
In some embodiments of the application, the probe on the first level sensor is illuminated when the collection liquid volume in the second buffer tank reaches a first set amount, optionally, the first set amount is 5% -20%, preferably 10%, of the second buffer tank volume.
In some embodiments of the application, when the collected liquid volume in the second buffer tank reaches a second set amount, the probe on the second liquid level sensor is lit up, and the control unit closes the fourth and fifth valves, simultaneously opens the sixth and ninth valves, opens the eighth valve, closes the seventh valve, activates the evacuation unit, optionally the second set amount is 50% -90%, preferably 80% of the second buffer tank volume.
In some embodiments of the present application, when the collected liquid volume in the second buffer tank is lower than the first set amount, the probe on the first liquid level sensor is turned off, the control unit closes the ninth valve and the sixth valve, opens the fourth valve and the fifth valve, closes the eighth valve, opens the seventh valve, and closes the vacuumizing unit. Thus, continuous automatic collection of the eluent in the resin column can be achieved.
In some embodiments of the application, the probe on the third level sensor is illuminated to stop collection when the collection in the reservoir reaches a third set amount, optionally 70% -90%, preferably 80% of the reservoir volume. Thus, continuous automatic collection of the eluent in the resin column can be achieved.
Additional aspects and advantages of the application will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the application.
Drawings
The foregoing and/or additional aspects and advantages of the application will become apparent and may be better understood from the following description of embodiments taken in conjunction with the accompanying drawings in which:
fig. 1 is a schematic flow diagram of the structure of a resin column eluent collection apparatus according to one embodiment of the present application.
Detailed Description
Embodiments of the present application are described in detail below, examples of which are illustrated in the accompanying drawings, wherein like or similar reference numerals refer to like or similar elements or elements having like or similar functions throughout. The embodiments described below by referring to the drawings are illustrative and intended to explain the present application and should not be construed as limiting the application.
In the description of the present application, it should be understood that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "clockwise", "counterclockwise", "axial", "radial", "circumferential", etc. indicate orientations or positional relationships based on the orientations or positional relationships shown in the drawings are merely for convenience in describing the present application and simplifying the description, and do not indicate or imply that the device or element being referred to must have a specific orientation, be configured and operated in a specific orientation, and therefore should not be construed as limiting the present application.
Furthermore, the terms "first," "second," and the like, are used for descriptive purposes only and are not to be construed as indicating or implying a relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defining "a first" or "a second" may explicitly or implicitly include at least one such feature. In the description of the present application, the meaning of "plurality" means at least two, for example, two, three, etc., unless specifically defined otherwise.
In the present application, unless explicitly specified and limited otherwise, the terms "mounted," "connected," "secured," and the like are to be construed broadly, and may be, for example, fixedly connected, detachably connected, or integrally formed; can be mechanically or electrically connected; either directly or indirectly, through intermediaries, or both, may be in communication with each other or in interaction with each other, unless expressly defined otherwise. The specific meaning of the above terms in the present application can be understood by those of ordinary skill in the art according to the specific circumstances.
In the present application, unless expressly stated or limited otherwise, a first feature "up" or "down" a second feature may be the first and second features in direct contact, or the first and second features in indirect contact via an intervening medium. Moreover, a first feature being "above," "over" and "on" a second feature may be a first feature being directly above or obliquely above the second feature, or simply indicating that the first feature is level higher than the second feature. The first feature being "under", "below" and "beneath" the second feature may be the first feature being directly under or obliquely below the second feature, or simply indicating that the first feature is less level than the second feature.
In one aspect of the application, a resin column eluate collection apparatus is provided. According to an embodiment of the application, referring to fig. 1, the apparatus comprises: the apparatus includes a resin column 100, a pipe 200, a first buffer tank 300, a second buffer tank 400, a liquid storage tank 500, a vacuum pumping unit 600, and a control unit 700.
According to an embodiment of the present application, a resin column 100 is filled with a resin packing, and has a feed port 101 and an eluent outlet 102. Specifically, the feed port 101 may be disposed at the top end of the resin column 100, the eluent outlet 102 may be disposed at the bottom end of the resin column 100, the solution to be separated is added into the resin column through the feed port, and then the solvent is added through the feed port to elute the solution to be separated. It should be noted that, those skilled in the art can choose the type of the resin column, the specific type of the resin filler and the specific type of the solvent according to actual needs, so long as the actual separation needs of the solution to be separated can be satisfied.
According to an embodiment of the present application, one end of the tube 200 is in communication with the eluent outlet 102, at least a portion of the tube 200 is a transparent tube, and the tube 200 has a first valve 21 and a second valve 22 thereon. Therefore, whether the solution is the target collection liquid can be judged according to the solution separated in the resin column, and the selective collection of the target collection liquid is realized by controlling the opening and closing of the first valve and the second valve.
According to one embodiment of the application, the conduit 200 comprises a main conduit 23, a first branch conduit 24 and a second branch conduit 25, wherein the main conduit 23 is connected to the eluent outlet 102, the first branch conduit 24 is connected to the main conduit 23, the first valve 21 is arranged on the first branch conduit 24, the second branch conduit 25 is connected to the main conduit 23, and the second valve 22 is arranged on the second branch conduit 25, wherein according to yet another embodiment of the application at least a part of the main conduit 23 is a transparent conduit. Specifically, the solution discharged from the eluent outlet at the bottom end of the resin column flows through the main pipeline, whether the solution is the target collecting liquid is observed through the transparent pipeline on the main pipeline, if the solution is not the target collecting liquid, the second valve on the second branch pipe is opened under the control of the control unit, the first valve on the first branch pipe is closed, the solution flowing through the main pipeline is used as a waste liquid discharging device until the solution flowing through the transparent pipeline on the main pipeline is the target collecting liquid color, at the moment, the second valve on the second branch pipe is closed under the control of the control unit, the first valve on the first branch pipe is opened, and the target collecting liquid enters the subsequent first buffer tank through the first branch pipe to be collected. It should be noted that, a person skilled in the art can select materials of the pipeline and the transparent pipeline according to actual needs, so long as the solution can be realized, the pipeline is not corroded, and the color of the transparent pipeline does not influence the color judgment of the solution.
According to an embodiment of the application, the first buffer tank 300 has a first eluent inlet 301, a first eluent outlet 302 and a third valve 31, a fourth valve 32 being arranged at the first eluent outlet 302, the first eluent inlet 301 being in communication with the other end of the pipe 200, the first eluent inlet 301 being in communication with the first branch 24 according to one embodiment of the application. Specifically, the third valve is used for adjusting the pressure in the first buffer tank, and the fourth valve is used for controlling the opening or closing of the first eluent outlet.
According to an embodiment of the application, the second buffer tank 400 has a second eluent inlet 401, a second eluent outlet 402, a fifth valve 41, a first level sensor 42 and a second level sensor 43, a sixth valve 44 being arranged at the second eluent outlet 402, the second eluent inlet 401 being connected to the first eluent outlet 302. Specifically, the first liquid level sensor and the second liquid level sensor are used for detecting the liquid level in the second buffer tank, when the target collection liquid volume in the second buffer tank reaches a first set amount, the probe on the first liquid level sensor is turned on, when the target collection liquid volume in the second buffer tank reaches a second set amount, the probe on the second liquid level sensor is turned on and starts alarming, the control unit closes the fourth valve and the fifth valve, simultaneously opens the sixth valve and the ninth valve, opens the eighth valve, closes the seventh valve, starts the vacuumizing unit, when the target collection liquid in the second buffer tank is lower than the first set amount, the probe on the first liquid level sensor is turned off and starts alarming, the control unit controls the ninth valve and the sixth valve to be closed first, the fourth valve and the fifth valve to be opened, simultaneously the seventh valve to be closed, and the vacuumizing unit to be closed, wherein the first set amount can be 5-20%, preferably 10%, and the second set amount can be 50-90%, preferably 80% of the second buffer tank volume.
According to an embodiment of the present application, the liquid storage tank 500 has an eluent inlet 501, a vacuum pumping port 502, an evacuation port 503, and a third liquid level sensor 51, a seventh valve 52 is disposed at the evacuation port 503, an eighth valve 53 is disposed at the vacuum pumping port 502, a ninth valve 54 is disposed at the eluent inlet 501, and the eluent inlet 501 is connected to the second eluent outlet 402. Specifically, the air exhaust port is used for adjusting the pressure in the liquid storage tank, the vacuum extraction port is used for adjusting the pressure in the whole device, the third liquid level sensor is used for detecting the liquid level height in the liquid storage tank, when the collected liquid volume in the liquid storage tank reaches a third set amount, a probe on the third liquid level sensor is lightened and starts to give an alarm, and the collection is stopped at the moment, wherein the third set amount can be 70-90%, preferably 80%, of the liquid storage tank volume.
According to the embodiment of the application, the vacuumizing unit 600 is connected with the vacuum pumping port 502 and is suitable for judging whether vacuum pumping is needed according to the liquid level in the second buffer tank, so that continuous and automatic collection of eluent in the resin column is realized. In particular, the person skilled in the art can choose the specific type of evacuation unit according to the actual needs, for example a vacuum pump can be used.
According to an embodiment of the present application, the control unit 700 is connected to the first to ninth valves 21 to 54 and the first to third liquid level sensors 42 to 51, respectively, and is adapted to control the opening and closing of the first to ninth valves and the alarm activation of the first to third liquid level sensors according to actual needs. In particular, the specific operation procedure of the control unit can be selected by a person skilled in the art according to actual needs.
According to an embodiment of the present application, the first to ninth valves may be pneumatic valves.
For the convenience of understanding, the specific operation of the resin column eluent collection device of the present application will be described below by taking the concentrate of the extraction of the cyclocarya paliurus as a target separation solution and taking an ethanol solution with a volume concentration of 60% as an example.
Firstly, loading desmodium styracifolium extraction concentrated solution into a resin column through a feed inlet, washing the column by adopting purified water, observing that the collected liquid is black and green through a transparent visible pipeline on a main pipeline, determining that the collected liquid is water-soluble impurities such as chlorophyll and the like, opening a second valve under the control of a control unit, closing a first valve, discharging waste liquid, further flushing the resin column by utilizing ethanol solution with the volume concentration of 60%, determining that the collected liquid is total flavonoids to be collected when the collected liquid is reddish brown through the transparent visible pipeline on the main pipeline, opening the first valve and a third valve under the control of the control unit, closing the second valve, discharging the collected liquid into a first buffer tank, opening a fourth valve and a fifth valve under the control of the control unit, closing a sixth valve, and allowing the collected liquid to enter the second buffer tank; when the volume of the collecting liquid in the second buffer tank reaches 10% of the volume of the tank body, the first liquid level sensing probe is lightened, and the collecting liquid is confirmed to enter the second buffer tank; when the collected liquid reaches 80% of the volume of the tank body, a probe on the second liquid level sensor is lightened, an alarm is started, at the moment, the fourth valve, the fifth valve and the seventh valve are closed under the control of the control unit, the sixth valve, the eighth valve and the ninth valve are opened, vacuumizing is carried out by starting the vacuumizing unit, and the eluent is pumped into the liquid storage tank through vacuum; when the collected liquid in the second buffer tank is lower than 10% of the tank in volume, the second liquid level sensing probe is turned off, an alarm is started, at the moment, a fifth valve is opened under the control of the control unit, a sixth valve, an eighth valve and a ninth valve are closed, a seventh valve is opened, and the vacuumizing unit is closed; when the pressure in the second buffer tank is recovered to normal pressure, the fourth valve is opened, the collected liquid stored in the first buffer tank is continuously discharged into the second buffer tank, the collected eluent is repeatedly collected according to the operation, when the collected liquid in the liquid storage tank reaches 80% of the volume of the tank body, the third liquid level sensing probe is lightened, the alarm is started, the collection is stopped, finally, when the 60% ethanol solution washes the resin chromatographic column by a certain multiple, the elution is stopped, and meanwhile, the collection is stopped when the liquid level is flush with the resin.
According to the resin column eluent collecting device provided by the embodiment of the application, the transparent pipeline is arranged on the pipeline between the eluent outlet on the resin column and the first buffer tank, whether the eluent is a target collecting liquid or not can be judged according to the color of the solution flowing through the transparent pipeline, so that the target collecting liquid can be selectively collected, meanwhile, the control unit can control the opening or closing of the valve on the first buffer tank according to the liquid level in the buffer tank, the control unit and the vacuumizing unit can judge whether the vacuum pumping is needed according to the liquid level in the second buffer tank, and therefore, the continuous automatic collection of the eluent in the resin column is realized, the labor intensity is obviously reduced, the working efficiency is improved, and the production requirements of new medicine development can be further met.
In the description of the present specification, a description referring to terms "one embodiment," "some embodiments," "examples," "specific examples," or "some examples," etc., means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the present application. In this specification, schematic representations of the above terms are not necessarily directed to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Furthermore, the different embodiments or examples described in this specification and the features of the different embodiments or examples may be combined and combined by those skilled in the art without contradiction.
While embodiments of the present application have been shown and described above, it will be understood that the above embodiments are illustrative and not to be construed as limiting the application, and that variations, modifications, alternatives and variations may be made to the above embodiments by one of ordinary skill in the art within the scope of the application.

Claims (9)

1. A resin column eluate collection apparatus comprising:
the resin column is filled with resin filler and is provided with a feed inlet and an eluent outlet;
a conduit having one end in communication with the eluent outlet, at least a portion of the conduit being a transparent conduit and having a first valve and a second valve thereon;
the first buffer tank is provided with a first eluent inlet, a first eluent outlet and a third valve, a fourth valve is arranged at the first eluent outlet, and the first eluent inlet is communicated with the other end of the pipeline;
the second buffer tank is provided with a second eluent inlet, a second eluent outlet, a fifth valve, a first liquid level sensor and a second liquid level sensor, a sixth valve is arranged at the second eluent outlet, and the second eluent inlet is connected with the first eluent outlet;
the liquid storage tank is provided with an eluent inlet, a vacuum extraction opening, an air exhaust opening and a third liquid level sensor, a seventh valve is arranged at the air exhaust opening, an eighth valve is arranged at the vacuum extraction opening, a ninth valve is arranged at the eluent inlet, and the eluent inlet is connected with the second eluent outlet;
the vacuumizing unit is connected with the vacuum pumping port;
the control unit is respectively connected with the first to ninth valves and the first to third liquid level sensors,
wherein,
when the volume of the collected liquid in the second buffer tank reaches a first set amount, the probe on the first liquid level sensor is lightened,
when the volume of the collected liquid in the second buffer tank reaches a second set amount, a probe on the second liquid level sensor is lightened, the control unit closes the fourth valve and the fifth valve, simultaneously opens the sixth valve and the ninth valve, opens the eighth valve, closes the seventh valve, starts the vacuumizing unit,
when the volume of the collected liquid in the second buffer tank is lower than the first set quantity, the probe on the first liquid level sensor is extinguished, the control unit firstly closes the ninth valve and the sixth valve, opens the fourth valve and the fifth valve, simultaneously closes the eighth valve, opens the seventh valve, closes the vacuumizing unit,
the first set quantity is 5-20% of the volume of the second cache tank;
the second set amount is 50-90% of the volume of the second buffer tank.
2. The apparatus of claim 1, wherein the conduit comprises:
the main pipeline is connected with the eluent outlet;
a first branch pipe connected to the main pipe, the first valve being disposed on the first branch pipe, and the first eluent inlet being connected to the first branch pipe;
and the second branch pipe is connected with the main pipeline, and the second valve is arranged on the second branch pipe.
3. The apparatus of claim 2, wherein at least a portion of the main conduit is a transparent conduit.
4. The device of claim 3, wherein the control unit opens or closes the first and second valves based on a change in color of the solution in the transparent tubing.
5. The apparatus of claim 1, wherein the first set amount is 10% of the second buffer tank volume.
6. The apparatus of claim 1, wherein the second set amount is 80% of the second buffer tank volume.
7. A device according to claim 3, wherein the probe on the third level sensor is illuminated and collection is stopped when the volume of collected liquid in the reservoir reaches a third set amount.
8. The device of claim 7, wherein the third set amount is 70-90% of the reservoir volume.
9. The device of claim 8, wherein the third set amount is 80% of the reservoir volume.
CN201710344184.7A 2017-05-16 2017-05-16 Resin column eluent collection device Active CN108854158B (en)

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