JP2019002798A - Liquid chromatography equipment - Google Patents

Abstract

A liquid chromatography apparatus having a mechanism for cleaning between an outer peripheral surface of a movable stopper and an inner peripheral surface of a column is provided. A liquid chromatography apparatus includes a column, a movable plug, a fixed plug, and a packing material. An O-ring 16 and a wear ring 15 are fitted on the movable stopper 4. In order to clean the space between the outer peripheral surface of the movable stopper 4 and the inner peripheral surface of the column 2, first to third flow path holes 21 to 23 are provided. The cleaning liquid from the first flow path hole 21 flows between the lower flange 15b and the O-ring 16, and after this portion is cleaned, it enters the recess 15d through the cut 15c, and the outer peripheral surface of the recess 15d and the lower flange 15b. The inner peripheral surface of the column 2 facing the upper surface, the lower surface of the upper flange 15a and the recess 15d is washed. The washing drainage flows out through the second flow path hole 22 and the communication hole 22a. [Selection] Figure 3

Description

  The present invention relates to a chromatography apparatus used in, for example, a separation and purification process of pharmaceuticals, fine chemicals, functional components, and the like, and more particularly to a liquid chromatography apparatus having a function of cleaning the outer peripheral surface of a movable stopper.

  As a liquid chromatography apparatus, an axial compression chromatography column that includes a movable stopper at the top of a column and moves the movable stopper downward to compactly fix the packing material is widely used. In the axial compression chromatography column, a seal part, for example, an O-ring is installed on the movable stopper to seal the inside of the column. There are cases where the O-ring is installed in one place of the movable stopper or in two places.

  In a chromatography column, for example, a liquid is introduced from a movable stopper passage, and the introduced liquid passes through a porous plate installed under the movable stopper, then reaches a filler layer, and the inside of the filler layer. And reaches the porous plate installed on the lower flange, and then is led out from the lower flange through the porous plate. When liquid is introduced from the lower flange inlet, the liquid reaches the porous plate installed on the lower flange, then reaches the filler layer through the porous plate, flows inside the filler layer, and moves. It passes through the porous plate installed under the stopper and is led out from the movable stopper liquid passage port.

  To pack the packing into an axial compression chromatography column, for example, the filler is dispersed in sterile water or a mobile phase solution to form a slurry, and then introduced into the column from the slurry inlet provided on the lower flange or the column body, for example. To do. Next, the movable stopper is moved from the lower flange side to the column upper end side for suction introduction, or the movable stopper is moved to a predetermined position in the column upper end direction, and the slurry is transported and introduced by a pump. After the slurry is introduced into the column, the slurry inlet is closed, the movable stopper is lowered, only the liquid is discharged from the porous plate, the slurry is concentrated, and after the predetermined consolidation, the movable stopper is By fixing, the filler is fixed. The fixed filler is subjected to, for example, a sterilization (sterilization) treatment with a drug solution or a drug solution drainage treatment with a mobile phase solution, and then a separation operation of a component to be purified is performed.

JP2015-72289A

  In the above-mentioned filler layer forming step, for example, sterile water, mobile phase solution, drug solution, etc. enter between the outer peripheral surface of the movable stopper and the inner surface of the column. There are concerns about the contamination of various metabolic components of bacteria and drugs. In other words, the O-ring is sealed between the movable stopper and the inner peripheral surface of the column, but when the movable stopper moves, the O-ring is slightly deformed or scratched, and the inner surface of the column is completely It is not uniform, and a slight gap or scratch is generated between the O-ring and the inner surface of the column. After the substance on the inner surface of the column enters the outer surface of the movable stopper or the packing is consolidated, the movable stopper is fixed. In the meantime, the repulsive force of the O-ring is slightly reduced and the substance on the inner surface side of the column enters the outer peripheral surface of the movable stopper, or the liquid passing pressure during separation of the purification target component (in the column and the column Substances on the inner surface of the column from the part where the repulsive force of the O-ring is slightly reduced by the external pressure difference) enter the outer surface of the movable stopper, and contaminate the purification target components by mixing drugs, bacteria, etc. There are concerns. However, until now, there has been no mechanism for easily and efficiently cleaning between the outer peripheral surface of the movable stopper and the inner peripheral surface of the column during or after the packing or compacting operation of the packing material.

  An object of the present invention is to provide a liquid chromatography apparatus having a mechanism for cleaning between the outer peripheral surface of a movable stopper and the inner peripheral surface of a column.

  In the liquid chromatography apparatus of the present invention, a first lid is attached to one end of a column, a second lid is attached to the other end, and a liquid inlet is provided in the first lid. The second lid is provided with a liquid outlet, and at least one of the lids is a movable stopper movable in the axial direction of the column axis. The movable stopper is provided with a cleaning liquid supply channel for supplying a cleaning liquid between the surface and the inner peripheral surface of the column.

  In one aspect of the present invention, the movable plug is provided with a discharge flow path for allowing the washing drainage to flow out between the outer peripheral surface of the movable plug and the inner peripheral surface of the column.

  In one aspect of the present invention, the cleaning liquid supply flow path is provided on one end side in the axial direction of the movable stopper, and the discharge flow path is provided on the other end side.

  In one aspect of the present invention, an O-ring is held on the outer peripheral surface of the movable stopper, and a part of the cleaning liquid supply channel is provided so as to supply the cleaning liquid to a gap along the O-ring.

  In one aspect of the present invention, the movable stopper includes a cylindrical wear ring that circulates around the movable stopper on an outer peripheral surface, and an end surface of the wear ring is in contact with the O-ring, and the outer periphery of the wear ring A recess is provided around the surface, and a cut is provided in the wear ring to communicate the gap between the O-ring and the wear ring and the recess.

  In one aspect of the present invention, at least one of the cleaning liquid supply channel and the discharge channel is open to the cut.

  According to the present invention, a very small gap between the outer peripheral surface of the movable stopper and the inner peripheral surface of the axial compression chromatography column for purifying pharmaceuticals, fine chemicals and functional components can be cleaned with the cleaning liquid. It is possible to prevent the occurrence of contamination due to contamination of the components with drugs, bacteria and metabolites of bacteria.

It is sectional drawing of the liquid chromatography apparatus which concerns on embodiment. It is a top view of the liquid chromatography apparatus which concerns on embodiment. It is the III-III sectional view taken on the line of FIG. It is the IV-IV sectional view taken on the line of FIG. It is the VV sectional view taken on the line of FIG. It is a perspective view of a wear ring. It is a fragmentary sectional view of the liquid chromatography apparatus concerning an embodiment. It is a fragmentary sectional view of the liquid chromatography apparatus concerning an embodiment. It is a perspective view of a wear ring.

  Hereinafter, embodiments will be described with reference to the drawings.

  FIG. 1 shows a liquid chromatography apparatus 1 according to the first embodiment.

  The liquid chromatography apparatus 1 includes a cylindrical column 2, a packing 3 filled in the column 2, a movable stopper 4 that is an upper lid disposed on the upper end side of the column 2, and a lower end side. A fixed plug 5 which is a lower lid body disposed, an upper filter 6 disposed on the lower surface of the movable plug 4, and a lower filter 7 disposed on the upper surface side of the fixed plug 5 are provided. The movable stopper 4 has a piston shape fitted inside the column 2. The fixing plug 5 is fixed to the lower end of the column 2.

  Both the movable plug 4 and the fixed plug 5 are disk-shaped, and an inflow port (opening) 8 is provided at the center of the movable plug 4 so as to penetrate the disk in the thickness direction. An outlet (opening) 12 is provided in the part.

  A space 9 is provided between the lower surface of the movable plug 4 and the upper filter 6, and a space 11 is provided between the upper surface of the fixed plug 5 and the lower filter 7.

  In this liquid chromatography apparatus 1, the liquid to be treated is supplied to the inside from the inlet 8, guided to the space 9, spreads over the entire upper surface of the filter 6, passes through the filter 6, and comes into contact with the filler 3. A chromatographic separation process is performed. The liquid that has passed through the filler 3 flows out through the filter 7, the space 11, and the outlet 12. On the contrary, the liquid to be treated may be introduced into the column 2 from the lower opening 12 and flowed out from the upper opening 8.

  In this embodiment, since a cleaning mechanism for cleaning between the outer peripheral surface of the movable stopper 4 and the inner peripheral surface of the column 2 is provided, this cleaning mechanism will be described with reference to FIGS.

  A stepped portion 4 a is provided over the entire periphery of the movable plug 4 on the upper surface side of the outer peripheral edge of the movable plug 4. A wear ring 15 is fitted on the outer peripheral surface of the stepped portion 4a.

  Further, an overhanging piece 4 b projecting radially from the lower end side of the outer peripheral edge of the movable plug 4 is provided over the entire circumference of the movable plug 4. An O-ring 16 is interposed between the bottom surface of the wear ring 15 and the protruding piece 4b.

  A first annular plate 17 and a second annular plate 18 are disposed on top of the stepped portion 4a and the wear ring 15 so as to overlap each other.

  A bolt 19 penetrating the first and second annular plates 17 and 18 is screwed into a bolt hole 20 provided in the stepped portion 4a. By screwing the bolt 19 into the bolt hole 20, the annular plates 17 and 18 push the wear ring 15 downward, and the O-ring 16 is held between the lower end surface of the wear ring 15 and the overhanging piece 4b. . The O-ring 16 is in watertight contact with the inner peripheral surface of the column 2 and the movable stopper 4, and the O-ring 16 provides a seal between the outer peripheral surface of the movable stopper 4 and the inner peripheral surface of the column 2. Done.

  As shown in FIG. 6, the wear ring 15 has a substantially cylindrical shape, and an upper flange 15a and a lower flange 15b project from the upper end and the lower end of the outer peripheral edge, respectively. The upper flange 15 a is continuously provided over the entire circumference of the wear ring 15. The lower flange 15b is provided with cuts 15c at equal intervals in the circumferential direction of the wear ring. Between the flanges 15a and 15b, it is the recessed part 15d which retreated to the center side of the wear ring 15 rather than the outer peripheral surface of each flange 15a and 15b.

  Further, the wear ring 15 is provided with flow path holes 21 and 22 for flowing the cleaning liquid. As shown in FIG. 3, the first flow path hole 21 extends downward from the upper end surface of the wear ring 15, bends obliquely downward toward the outer peripheral end of the lower flange 15 b near the lower end of the wear ring 15, and An opening is formed in the vicinity of the outer peripheral edge of the lower end surface of the flange 15b or at the intersection angle edge between the lower end surface and the outer peripheral surface.

  As shown in FIG. 4, the second flow path hole 22 extends downward from the upper end surface of the wear ring 15, then bends in the radial direction of the wear ring 15, and near the corner of the intersection between the recess 15 and the upper flange 15 a. Is open.

  The annular plate 17 is made of metal and the annular plate 18 is made of a synthetic resin such as a fluororesin, but is not limited thereto. In the annular plates 17 and 18, communication holes 21 a and 22 a that allow the flow passage holes 21 and 22 to communicate with the upper portion of the annular plate 18 are provided in the vertical direction. The flow paths 21 and 22 and the communication holes 21a and 22a are provided in plural numbers (for example, 3 to 20 pieces each, four pieces in this embodiment) at regular intervals in the circumferential direction of the wear ring 15.

  The movable plug 4 is provided with a third flow path hole 23 whose front end opens on the outer peripheral surface of the overhanging piece 4b. The third flow path hole 23 extends downward from the upper surface of the movable plug 4 on the center side with respect to the stepped portion 4a, and then extends in the radial direction of the movable plug 4 to the outer peripheral surface of the protruding piece 4b. Exist. As shown in FIG. 2, a plurality of third flow path holes 23 are provided at regular intervals in the circumferential direction of the movable plug 4 (for example, 4 to 20 pieces, eight in this embodiment).

  When the cleaning liquid is supplied through the communication hole 21a and the first flow path hole 21, the cleaning liquid flows between the lower flange 15b and the O-ring 16, and after cleaning this portion, enters the recess 15d through the cut 15c. The outer peripheral surface of the recess 15d, the upper surface of the lower flange 15b, the lower surface of the upper flange 15a, and the inner peripheral surface of the column 2 facing the recess 15d are washed. The washing drainage flows out through the second flow path hole 22 and the communication hole 22a.

  When the cleaning liquid is supplied to the third flow path hole 23, the cleaning liquid flows out between the outer peripheral surface of the overhanging piece 4b and the inner peripheral surface of the column 2, and this portion is cleaned, and a part of the cleaning liquid is overhanging. It flows between the piece 4b and the O-ring 16, and this portion is cleaned.

  Note that the cleaning liquid may be introduced into all the third flow path holes 23, the cleaning liquid is supplied to a part (for example, half) of the third flow path holes 23, and the cleaning waste liquid is discharged from the remaining third flow path holes 23. May be spilled.

  In this way, by allowing the cleaning liquid to flow through the flow path holes 21 to 23, the space between the outer peripheral surface of the movable plug 4 and the inner peripheral surface of the column 2 can be cleaned.

  7, 8 and 9 show the cleaning mechanism of the liquid chromatography apparatus according to the second embodiment. 7 is a sectional view of a portion corresponding to FIG. 3, and FIG. 8 is a sectional view of a portion corresponding to FIG. FIG. 9 is a perspective view of the wear ring 15 '.

  In this embodiment, the wear ring 15 ′ is smaller in height than the wear ring 15 of the first embodiment, and the upper end surface of the wear ring 15 ′ is lower than the upper end surface of the step 4a of the movable plug 4 ′. Is located. An O-ring 26 is disposed so as to contact the upper end surface of the wear ring 15 'and the outer peripheral surface of the step portion 4a. The annular plates 17 and 18 are arranged so as to hold down the O-ring 26 from above, and are fixed to the movable stopper 4 ′ by bolts 19 (not shown in FIGS. 7 to 9) as in the first embodiment. Yes. By screwing the bolt 19 into the bolt hole 20, the O-ring 26 is clamped between the wear ring 15 'and the annular plate 17, and the O-ring 16 is clamped between the wear ring 15' and the overhanging piece 4b. The The O-rings 16 and 26 are in watertight contact with the outer peripheral surface of the movable stopper 4 ′ and the inner peripheral surface of the column 2.

  A cut 15e is provided in the upper flange 15a of the wear ring 15 '. The cut 15e communicates the upper surface side of the upper flange 15a and the recess 15d. A plurality of (for example, 4 to 20) cuts 15e are provided at equal intervals in the circumferential direction of the upper flange 15a.

  In this embodiment, the first flow path hole 31 includes an intersection between the outer peripheral surface of the lower flange 15b and the lower end surface or the vicinity of the outer peripheral surface of the lower end surface of the lower flange 15b, and the inner peripheral surface of the wear ring 15 ′. It is penetrated diagonally so as to communicate.

  Further, the second flow path hole 32 is provided in the radial direction of the wear ring 15 ′ so as to communicate the cut 15 e with the inner peripheral surface of the wear ring 15 ′. The step portion 4a is provided with communication holes 31a and 32a so that the first flow path hole 31 and the second flow path hole 32 communicate with the inner peripheral surface of the step portion 4a.

  Other configurations of the second embodiment are the same as those of the first embodiment, and the same reference numerals denote the same parts.

  The cleaning method using the cleaning liquid through the third flow path hole 23 in the second embodiment is the same as that in the first embodiment. Even in this case, the cleaning liquid may be supplied to all the third flow path holes 32, the cleaning liquid may be supplied to some of the third flow path holes 32, and the remaining third flow path holes 32 may be discharged to the drainage flow. It may be a road.

  A cleaning liquid is supplied to the first flow path hole 31 from the communication hole 31a, and first, the space between the O-ring 16 and the lower flange 15b is cleaned. The cleaning liquid then flows from the cut 15c into the recess 15d, and this portion is cleaned. The cleaning liquid then flows into the cut 15e, and a part thereof flows out through the second flow path hole 32 and the communication hole 32a. The remaining portion of the cleaning liquid flows into the space between the upper flange 15a and the O-ring 26 from the cut 15e. After this portion is cleaned, it flows out through the second flow path hole 32 and the communication hole 32.

  Alternatively, the cleaning liquid may be supplied to some of the second flow path holes 32 and the cleaning waste liquid may be discharged from the remaining second flow path holes 32. Alternatively, the cleaning liquid may be supplied from the second flow path hole 32 and the cleaning drainage liquid may be discharged from at least a part of the first flow path hole 31.

  As described above, also in the second embodiment, the space between the movable stopper 4 ′ and the inner peripheral surface of the column 2 is cleaned with the cleaning liquid.

  The above-described embodiment is an example of the present invention, and the present invention may be configured other than illustrated. In the above embodiment, the movable stoppers 4 and 4 ′ are on the upper side of the column 2. However, the movable stoppers 4 and 4 ′ may be on the lower side.

DESCRIPTION OF SYMBOLS 1 Liquid chromatography apparatus 2 Column 3 Packing agent 4, 4 'Movable stopper 5 Fixed stopper 15, 15' Wear ring 15a Upper flange 15b Lower flange 15c, 15e Cut 15d Recess 16, 26 O-ring 21, 31 1st flow hole 22, 32 Second channel hole 23 Third channel hole

Claims (6)

A first lid is attached to one end of the column, and a second lid is attached to the other end,
The first lid is provided with a liquid inlet, and the second lid is provided with a liquid outlet. At least one of the lids is movable in the column axis direction. In a liquid chromatography device that is a stopper,
A liquid chromatography apparatus, wherein a cleaning liquid supply channel for supplying a cleaning liquid between an outer peripheral surface of the movable stopper and a column inner peripheral surface is provided in the movable stopper.   2. The liquid chromatography apparatus according to claim 1, wherein the movable stopper is provided with a discharge passage for allowing the washing drainage liquid to flow out between the outer peripheral surface of the movable stopper and the inner peripheral surface of the column.   3. The liquid chromatography apparatus according to claim 2, wherein the cleaning liquid supply flow path is provided on one end side in the axial line direction of the movable stopper, and the discharge flow path is provided on the other end side.   4. The O-ring is held on the outer peripheral surface of the movable stopper according to claim 1, and a part of the cleaning liquid supply channel is provided so as to supply the cleaning liquid to a gap along the O-ring. A liquid chromatography apparatus. In Claim 4, the movable stopper is provided with a cylindrical wear ring around the movable stopper on the outer peripheral surface,
The end surface of the wear ring is in contact with the O-ring,
A recess is provided around the outer peripheral surface of the wear ring,
A liquid chromatography apparatus, wherein a cut between the O-ring and the wear ring and the recess is provided in the wear ring.   6. The liquid chromatography apparatus according to claim 5, wherein at least one of the cleaning liquid supply channel and the discharge channel is opened in the cut.

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