JP2817610B2 - Ring chromatography equipment - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a filler having a difference in biological or physicochemical interaction with each component in a liquid to be separated such as affinity (sometimes referred to as a separating agent). But,
The liquid to be separated is passed through the annularly filled annular filling portion, and is contained in the liquid to be separated by utilizing the difference in moving speed caused by the difference in biological or physical interaction with each component. The present invention relates to an improvement in a cyclic chromatography apparatus for continuously separating two or more components.

[0002]

2. Description of the Related Art Conventionally, for separation of two or more components contained in a liquid to be separated, a porous polymer gel, a hydrophilic polymer gel having a hydrophilic group, an octadecyl group, a phenyl group and the like are bonded to a silica gel surface. Chromatography using a filler such as chemically bonded silica gel to separate each component using the difference in solubility of each component; using a filler such as silica gel to utilize each component's absorption energy difference Chromatography; separation of each component using a difference in asymmetric discrimination ability of each component using a filler such as chemically bonded silica gel in which a chiral ligand conjugate is bonded to silica gel; Hydroxyapatite that separates each component using the difference in adsorption energy and ionic affinity of each component using hydroxyapite filler Chromatography: ion exchange chromatography that separates each component using the difference in ionic affinity of each component using a filler such as a polystyrene gel derivative represented by an ion exchange resin, a chemically bonded silica gel, or a hydrophilic polymer gel. (Or ion chromatography); size exclusion chromatography in which each component is separated using a difference in molecular size of each component using a gel-filtration-type filler such as a chemically bonded silica gel or a hydrophilic polymer gel; Furthermore, using a filler such as a hydrophilic polymer gel, the biological affinity of each component (for example, between an enzyme and a substrate, an inhibitor or an expression factor, or between an antigen and an antibody, Affinity chromatography, which separates each component by utilizing the difference in specific interaction, is used widely.

[0003] Usually, the above-mentioned chromatographic operation involves:
This is a batch system in which a cylindrical tube is filled with the above-mentioned filler to form a stationary phase, and a liquid to be separated to be separated passes through the stationary phase. That is, after the liquid to be separated is supplied to one end of the stationary phase, an eluent that acts as a mobile phase for the filler that is the stationary phase and desorbs and moves the components trapped in the stationary phase is supplied. . By the flow of the eluent, the liquid to be separated is separated and developed, and the liquid to be separated has the smallest biological or physicochemical interaction force (capture method) with the packing material. The liquid component to be separated that flows out of the stationary phase together with the eluent and has the greatest biological or physicochemical interaction with the packing material finally flows out of the stationary phase together with the eluent.

As described above, the chromatography operation is
The supply of the liquid to be separated is intermittent, and the supply of the liquid to be separated and the supply of the eluent must be performed alternately, resulting in poor operability. Therefore, conventionally, as a method of solving the above-mentioned drawbacks of the batch system, so as to form a cross flow with the flow direction of the eluent,
A cross flow method has been proposed in which the liquid to be separated can be continuously supplied by moving the filler, and continuous separation of two or more components can be performed. In this method, the eluent and the flow of the liquid to be separated flowing from the upper part to the lower part of the annular filling part in which the filler is annularly filled are relatively cross-flowed,
This is carried out by a circular chromatography apparatus in which the circular packing section is rotated (Japanese Patent Application Laid-Open Nos. 61-164156, 62-42048, 2-189).
458, JP-A-4-227027, JP-A-4-227820, etc.).

[0005] The principle of the above cyclic chromatography will be described with reference to FIG. In this method, a gap between the inner cylinder 2 and the outer cylinder 3 of the double cylinder 1 rotating in the circumferential direction is filled with a filler to form an annular filling portion 4, and the annular filling portion 4 Continuously supply the liquid to be separated and the eluent,
The component separated from the lower part is continuously taken out.

More specifically, an eluent supply pipe 5 (a plurality of eluents) for supplying an eluent and a liquid supply pipe 6 for supplying a liquid to be separated (see FIG. 1) are provided above the annular filling section 4 in which the filler is filled in a circular shape. Are provided, and a plurality of outlets 7 are provided at the lower end of the annular filling portion 4 at predetermined intervals so as to collect the separated liquid separated through the annular filling portion 4. The annular filling portion 4 is rotating at an arbitrary constant speed in the direction indicated by the arrow P, and the liquid to be separated and the eluent are supplied to the separation liquid supply pipe 6 fixed above the annular filling portion 4, respectively.
And from the eluent supply pipe 5 continuously.

For example, when the liquid to be separated contains the components A, B and C and the affinity of each component in the liquid to be separated and the filler has a relationship of A <B <C, By the operation, the eluent flow and the filler flow become a cross flow, and the liquid to be separated supplied to the upper part of the filler in the annular filling part 4 flows downward by the eluent flow, but the filler flows with respect to the eluent flow. Each component in the liquid to be separated flows helically due to affinity with the filler because the components move relatively vertically (perpendicularly). As a result, C having a high affinity for the filler
The components elute at a position distant from the supply port of the liquid-to-be-separated liquid supply pipe 6, the A component having low affinity elutes at a position close to the supply port, and the B component elutes from an intermediate position. The elution position is a fixed position determined by the moving speed of the filler and the eluent, that is, a position at an angle determined from the supply port of the liquid to be separated. In this way, the liquid to be separated can be separated into three components and taken out from the outlet 7 below the annular filling part 4.

The mechanism of the separated liquid take-out section 8 which receives and takes out each component separated from the outflow port 7 comprises a plurality of collector vessels fixed below the annular filling section 4 in accordance with the annular shape thereof. . That is, while the annular filling portion 4 and the outlet 7 rotate at an arbitrary constant speed in the direction indicated by the arrow P, the liquid supply pipe 6 to be separated and the collector container are in a fixed and stationary relationship with each other. Has become. This collector container may be provided at least below the position where each component elutes, but usually, a plurality of collector containers are integrally joined and formed in many cases according to the annular shape of the annular filling portion 4.

[0009]

However, when actually operating the above-described cyclic chromatography apparatus,
The outlet from which the separated components flow out was not always constant, and the outflow positions of the components varied. Even if the filter (sintered wire mesh, glass filter) used in the conventional batch type liquid chromatography, which is said to be formed extremely uniformly, is attached to the outlet base at the lower end of the annular filling portion, it is still operated. The outflow positions of the components varied, and each component could not be efficiently recovered.

When the cause is examined in detail, the following (a) to (c) show that the flow rate of the eluent flowing down in the packing material is not uniform over the entire circumference of the annular packing section 4. It turned out to be. (A) There is no filler having a completely uniform particle size. (B) Completely uniform filling of the filler is not possible.

(C) There is no filter having a completely uniform hole diameter. If the eluent flow rate is not uniform, each component in the liquid to be separated will
It cannot flow in a fixed spiral, and therefore the outflow position of each component fluctuates. As a result, there arises a problem that each component cannot be efficiently separated and recovered. That is, in cyclic chromatography, it is very important from the viewpoint of separation efficiency that the flow rate of the eluent flowing down in the packing material be kept uniform without disturbance over the entire circumference of the cyclic packing section 4.

In the conventional batch type liquid chromatography, a fine column is often used, and a column having a large diameter is rarely used. The problem is unique to cyclic chromatography. Accordingly, the present invention has been made in view of the above-described conventional problems, and provides a cyclic chromatography apparatus that can make the flow rate of an eluent flowing down into a packing material constant and can efficiently separate components to be separated. The purpose is to do.

[0013]

For this purpose, the cyclic chromatography apparatus according to the first aspect of the present invention is provided with an annular packing portion which is filled with a packing material in a ring shape, and is provided at a lower end of the annular packing portion. An eluent supply pipe for supplying an eluent to at least the annular filling part, and a separated liquid supply pipe for supplying a liquid to be separated to be separated, and an outlet for discharging the discharged liquid. in annular chromatography system provided in, or flow to all of the outlet
A valve is provided on the pipe attached to the outlet .

That is, according to the first aspect of the invention, the liquid supply pipe to be separated is fixed, and the annular chromatography apparatus in which the annular filling section rotates and the liquid supply pipe to rotate rotates to fix the annular filling section. Any type of cyclic chromatography apparatus may be used. Further, the valve may be any valve as long as it can adjust the flow rate.In general, the valve opens and closes, and can be used as an on-off valve such as a gate valve or a ball valve which is not often used for adjusting the flow rate. Is preferably a flow control valve such as a global valve or a needle valve.

The annular chromatography apparatus according to the second aspect of the present invention includes an annular packing portion filled with a packing in an annular shape, and an outlet provided at a lower end of the annular packing portion for discharging a liquid discharged from the annular packing portion. An eluent supply pipe for fixing the annular filling portion and supplying an eluent to at least the annular filling portion, and supplying a liquid to be separated while moving along the annular shape of the annular filling portion. It provided a separation target liquid supply pipe to the annular packing unit top, young properly to all the outlet
Has a configuration in which a flow control device is provided in a pipe attached to the outlet .

The above-mentioned flow rate control apparatus includes an embodiment in which the flow rate adjustment described later is performed by making the differential pressure constant, and an apparatus in which the valve opening is automatically adjusted based on the measured flow rate value. Any size can be used as long as it is small.

[0017]

In the cyclic chromatography apparatus according to the first aspect of the present invention, the eluent is supplied to the upper portion of the packing section (the liquid to be separated is supplied) in order to make the flow rate of the eluent flowing down in the packing uniform. Or supply may not be provided), and the opening of a flow control valve (valve) is adjusted. In a small-scale device, the effluent drips from the outlet or a pipe attached to the outlet via a valve, so that in order to adjust the flow rate, the number of drops per unit time is reduced. Adjust the opening of the valve so that the number of drops is counted. In order to increase the accuracy of a large-scale device or to increase the accuracy, a flowmeter is provided downstream of the valve, and the valve opening is adjusted based on the value of the flowmeter. In this case, depending on the liquid to be separated, the outlet or the outlet may be attached to the outlet.
It is not necessary to attach a flow meter to all of the pipes that have been measured, and the flow rate does not change so much in the vicinity of the flow rate measurement even for a plurality of pipes. The initial objective can be achieved by visually adjusting the flow condition. Also, prepare a movable flow meter and attach it to one outlet or the outlet.
After measuring the flow rate of the cut pipe , remove the flow meter and attach the flow meter to the next outlet or the outlet.
And connected to the outlet or the outlet
It is also possible to adjust the opening degree of the valve of the pipe that has been cut.

In the annular chromatography apparatus according to the second invention, the outlet or the outlet is attached to the outlet.
Adjust the settings of all flow control devices on the pipe . As a result, the flow rate of the eluent (including the liquid to be separated) flowing down into the packing material can be maintained uniformly without being disturbed over the entire circumference of the annular packing portion, and each component in the liquid to be separated is formed into a fixed spiral. The components can flow efficiently, and the outflow position of each component does not fluctuate and can be efficiently recovered.

[0019]

Embodiments of the present invention will be described below with reference to the drawings. FIG. 1 is a perspective sectional view showing one embodiment of the first invention. The main body 10 of the annular chromatography apparatus includes a body 11, an upper lid 12 at an upper end of the body 11, and a gantry 13 at a lower end of the body 11. In FIG. 1, the middle part of the body 11 is not shown.

The body 11 is composed of an inner cylinder 14 and an outer cylinder 15. A predetermined gap is provided between the inner cylinder 14 and the outer cylinder 15, and forms a part of an annular filling portion 34 described later. doing. The inner cylinder 14 is provided with a circular plate portion 1 facing vertically.
6 and an annular plate portion 17, and an inner peripheral wall portion 18 and an outer peripheral wall portion which are respectively disposed inside and outside so as to connect the outer peripheral portions of the circular plate portion 16 and the annular plate portion 17 to each other. 19. A jacket 20 is formed between the inner peripheral wall 18 and the outer peripheral wall 19. That is, nozzles (not shown) are provided at upper and lower portions inside the inner peripheral wall portion 18, respectively, and a refrigerant, a heat medium, and a fluid made constant in a constant temperature bath or the like flow through the jacket portion 20 to reach a predetermined temperature. The jacket part 2
Numeral 0 controls a temperature holding function of the annular filling portion 34 described later.

At the center of the circular plate 16 on the upper side of the inner cylinder 14, a through hole 21 for a rotating shaft 44, which will be described later, is formed.
A circular hole 22 is formed in the center of the lower annular plate portion 17. The outer cylinder 15 is provided between the annular plate portions 23 and 24 so that the annular plate portions 23 and 24 vertically opposed to each other and the inner peripheral portions of the annular plate portions 23 and 24 are connected to each other. It comprises an inner peripheral wall 25 and an outer peripheral wall 26 disposed inside and outside. A jacket 27 is formed between the inner peripheral wall 25 and the outer peripheral wall 26. That is, nozzles (not shown) are provided on the upper and lower portions of the outer peripheral wall portion 26, respectively, so that a refrigerant, a heat medium, and a fluid made constant in a constant temperature bath or the like flow through the jacket portion 27 and reach a predetermined temperature. The jacket portion 27 serves to maintain the temperature of an annular filling portion 34, which will be described later, similarly to the jacket portion 20 on the inner cylinder 14 side.

The upper lid 12 is formed of a circular plate. The gantry 13 is formed of an annular plate, and is fixedly supported by a stand (not shown) or the like. And the upper lid 1
2 is attached to the upper annular plate portion 23 of the outer cylinder 15 with an O-ring 29 interposed therebetween by a plurality of bolts and nuts 28 provided in the circumferential direction. 15 It is air-tightly joined to the upper end.

A plurality of bolts and nuts 30 provided in the circumferential direction attach the lower annular plate portion 24 of the outer cylinder 15 to the gantry 13 and a plurality of bolts and nuts 31 provided in the circumferential direction. , The annular plate portion 1 of the inner cylinder 14
7 is attached. An O-ring 32 is provided on the joint surface between the gantry 13 and the lower annular plate portion 24 of the outer cylinder 15.
An O-ring 33 is interposed on the joint surface of the inner cylinder 14 and the annular plate portion 17 of the inner cylinder 14, and the gantry 13 is airtightly joined to the lower end of the outer cylinder 15 and the lower end of the inner cylinder 14 of the body 11. Have been.

By configuring the apparatus main body 10 as described above, the upper surface of the inner cylinder 14, that is, the upper surface of the upper circular plate portion 16 is positioned lower by the upper end position of the outer cylinder 15, and the outer cylinder 1
Between the inner cylinder 5 and the inner cylinder 14, an annular filling portion 34 in which the filler is annularly filled is formed. In the center of the upper surface of the upper lid 12, a raw material supply cylinder 37 composed of a cylindrical portion 35 and a disk portion 36 joined to the upper end of the cylindrical portion 35 is integrally formed. A support portion 38 is fixedly mounted on the upper surface of the disk portion 36 of the raw material supply cylinder 37. Further, a rotating shaft 44 to be described later is provided on the upper end of the support portion 38 via a support base 39.
Drive device 40 is held.

The driving device 40 comprises a stepping motor 41, a power transmission device 42 composed of a pair of sprockets 42a and a chain 42b, and a worm gear 43, and transmits the rotational driving force of the stepping motor 41 to the power transmission device 42. The worm gear 43 is transmitted to the worm gear 43 through the worm gear 43 to rotate the worm gear 43. A rotating shaft 44 extending in the vertical direction is connected to the shaft of the worm gear 43. The rotating shaft 44 is connected to the material supply cylinder 37,
8, penetrates through the upper lid 12, the inner cylinder 14, and the center of the pedestal 13 and protrudes below the pedestal 13.

Inside the concave portion 38a of the support portion 38,
A block 45 for holding the rotating shaft is inserted. The block 45 has a rotating shaft 44 passing therethrough.
Are fixed by connecting bolts 46. A bearing 47 for supporting the block 45 and a bearing 48 for positioning the block are inserted and arranged below the block 45 inside the concave portion 38a of the support portion 38.

The inside of the cylindrical portion 35 of the raw material supply cylinder 37 and the inside of the cylindrical portion 49 protruding from the center of the upper surface of the circular plate portion 16 of the inner cylinder 14 are provided for feeding the raw material (the liquid to be separated). Block 50 is inserted. The block 50 is fixedly attached to the outer periphery of the rotating shaft 44 passing through the center of the block 50 by a connection bolt 51. Between the inner peripheral surface of the cylindrical portion 35 of the raw material supply cylinder 37 and the outer peripheral surface of the block 50, a pair of upper and lower seal packings 52 for preventing raw material from leaking to the outside, which will be described later, and between the seal packings 52, 52. And a spacer 53 for reducing a space portion (dead portion) of the raw material inflow line. On the lower surface of the upper lid 12, a pressing fixing member 54 that presses and supports the seal packing 52 is mounted. A seal packing 55 is provided between the inner peripheral surface of the cylindrical portion 49 of the inner cylinder 14 and the outer peripheral surface of the block 50 to prevent the raw material from leaking outside. Further, the block 50 is provided below the block 50 inside the cylindrical portion 49.
A positioning bearing 56 is inserted and arranged. A pressing fixing member 57 for the seal packing 55 is mounted on the upper surface of the cylindrical portion 49.

In the peripheral wall of the cylindrical portion 35 of the raw material supply cylinder 37, a hole 58 serving as a raw material entrance is opened.
A boss 59 is fixedly attached to the outer peripheral surface of the cylindrical portion 35 so as to surround the hole 58. This boss portion 59
A raw material inlet pipe 60 is fixedly attached to a tip end of the pipe by a pipe fixing nut 61. A seal packing is loaded between the outer peripheral surface of the cylindrical portion 35 around the hole 58 inside the boss portion 59 and the tip of the raw material inlet pipe 60. A space between the pair of upper and lower seal packings 52, 52 communicating with the hole 58 inside the cylindrical portion 35 is formed as a space of a raw material inflow line. The block 50 has an opening at the outer peripheral surface of the block 50 so that one end thereof communicates with the space, and the other end is formed at a space formed between the upper part of the inner cylinder 14 and the upper lid 12 of the block 50. A raw material passage 62 that opens as a hole 63 is formed on the outer peripheral surface of the located portion. A boss 64 is fixedly attached to the outer peripheral surface of the block 50 so as to surround the hole 63. A raw material feed pipe 65 is fixedly attached to the tip of the boss 64 by a pipe fixing nut 66. A seal packing 6 is provided between the outer peripheral surface of the block 50 around the hole 63 inside the boss 64 and the base end of the raw material feed pipe 65.
7 are loaded. The raw material feed pipe 65 extends horizontally from the outer peripheral surface of the block 50 to a space formed between the upper portion of the inner cylinder 14 and the upper lid 12, and is bent downward. Injected into the filler.

The raw material passage 62 and the raw material feed pipe 6
5 means that the raw material (the liquid to be separated) is filled in the annular filling portion 34
A liquid supply pipe to be supplied upward is formed. The gantry 1
3, at a plurality of positions corresponding to the annular filling portion 34, an outlet 68 communicating with the annular filling portion 34 is formed.
The outlet 68 is provided with a valve (valve) 69.

The filter 70 is provided inside the outlet 68.
Is interposed. The configuration of the valve 69 will be described with reference to FIG. The valve 69 includes a valve body 71 and a valve body 72. The valve body 71 includes an inner cylinder 71A and an outer cylinder 71B. An external thread 7 is provided on the outer peripheral surface of the upper end of the inner cylinder 71A.
1a is formed, and the male screw portion 71a is formed downstream of the outlet 68 of the gantry 13 so that the inner cylinder 71A is fixed to the gantry 13 by screw fitting with the screw portion 13a. And 71A. A male thread 71b is formed on the outer peripheral surface of the lower end of the inner cylinder 71A.
b formed on the inner peripheral surface of the upper end of the outer cylinder 71B.
1c is screw-fitted, so that the outer cylinder 71B is
A is slidably coupled to A, and the inner cylinder 71A and the outer cylinder 71B communicate with each other.

The valve body 72 includes a needle portion 72a,
As shown in FIG. 2 (B), the needle portion 72 includes a perforated portion 72c having a circular hole 72b.
a and the dish-shaped portion 72c are formed independently. The needle portion 72a is inserted and arranged in a space 73 formed at a joint portion between the inner cylinder 71A and the outer cylinder 71B, and the tip thereof is located inside the inner cylinder 71A. The perforated portion 72c is inserted and arranged on a step 71d of the outer cylinder 71B below the needle portion 72a of the space 73.

In the valve 69 having such a configuration, the outer cylinder 71B
Is rotated with respect to the inner cylinder 71A, and the inner cylinder 71 of the outer cylinder 71B is rotated.
When the screw fitting position with respect to A is changed, the space 7
3 changes in size. Therefore, when the space 73 is enlarged, the needle portion 72a and the perforated portion 72c slide downward by their own weight, whereby the gap (passage) between the needle portion 72a and the inner side of the inner cylinder 71A increases. The flow rate is largely adjusted. Conversely, when the space 73 is reduced, the needle portion 72a and the dish-shaped portion 72c are pushed up and slid upward, whereby the gap (passage) between the needle portion 72a and the inner side of the inner cylinder 71A is reduced. Therefore, the flow rate is adjusted to be small.

On the other hand, in FIG.
An eluent supply pipe 74 for supplying an eluent (eluent) to the annular filling portion 34 through a space formed between the upper part of the inner cylinder 14 and the upper lid 12 is integrally attached therethrough. ing. A disk-shaped first receiving tray 75 is provided below the gantry 13. The central portion of the pan 75 is
Is fastened and fixed to a lower end portion of the shaft by a nut 76 so as to rotate integrally with the rotating shaft 44. A plurality of sorting containers 77 are attached inside the first receiving tray 75. The separation container 77 collects the separated components discharged from the outlet 68 of the annular filling portion 34,
On a bottom wall slightly inward from the side plate (that is, at the center of the bottom wall of the sorting container 77), an extraction pipe 77a for guiding the collected components to a second receiving tray 78 disposed below the extraction pipe 77a.
Are provided. The bottom wall of the first receiving tray 75 has a hole 75 through which the extraction pipe 77a of each sorting container 77 passes.
a are arranged in a plurality of rings at predetermined intervals.
The take-out pipe 77 of the sorting container 77 penetrating this hole 75a
a is an effluent introduction pipe 83 for guiding the recovered components to a component receiver 80 of the second tray 78 described below.
It is connected to the. Further, a pipe 86 is attached downward at a position near the rotation shaft 44 on the bottom wall of the first receiving tray 75, and the unnecessary eluent discharged from the outlet 68 of the annular filling portion 34 is discharged to the second lower portion. Of the receiving tray 78 described later.

It is to be noted that the sorting container 7 is used in accordance with the number of separated components.
7 is provided in the first pan 75, so that the sorting container 7
A rubber stopper 175 is inserted into a hole 75a of the first receiving tray 75 through which the take-out pipe 77a does not penetrate, and is liquid-tight. Further, the inner periphery of the hole 75a of the first pan 75 and the hole 75a
There is a gap between the outlet pipe 77a and the outer periphery of the take-out pipe 77a. However, since the take-out pipe 77a is attached to the bottom wall surface (center of the bottom wall of the take-up vessel 77) slightly inward from the side plate of the take-up vessel 77, the bottom of the take-up vessel 77 near the take-out pipe 77a is provided. The lower surface of the wall and the upper surface of the first receiving tray 75 are in close contact with each other, forming a kind of sealing mechanism, and the unnecessary eluent discharged from the outlet 68 of the annular filling portion 34 flows into the first receiving tray 75. However, there is no leakage from the gap between the inner periphery of the hole 75a and the outer periphery of the extraction pipe 77a. Also,
If the eluent is leaky, take out the pipe 77 if necessary.
a Sealing tape is wound around the outer periphery of the
It is inserted into 5a and made liquid-tight.

Below the first tray 75, the second tray 78 is fixedly supported by a stand or the like (not shown) as described above. A plurality of partition walls 79 which are annularly continuous in the circumferential direction are provided concentrically inside the receiving tray 78, and the inside of the receiving tray 78 is formed of a plurality of annular grooves formed by the partition walls 79. A container 80 is formed. An outlet 81 is opened at a portion of the bottom wall of the second tray 78 corresponding to each of the component receivers 80, and an outlet pipe 82 is connected to the outlet 81. Further, below the outlet pipe 82, a product receiver 84 for each component is arranged.

A circular container 85 for collecting the unnecessary eluent discharged from the pipe 86 of the first tray 75 is formed in the central portion inside the second tray 78. A pipe 87 is connected to discharge the unnecessary eluent from the container portion 85 to the outside. As is apparent from the above description, the annular chromatography apparatus having such a configuration includes the supply pipe for the liquid to be separated (the raw material passage 62 and the raw material feed pipe 65) and the separation vessel 7 serving as the separated liquid takeout section.
7 rotates, and an annular filling portion 34 in which the filler is annularly filled.
Is fixed. This annular chromatography apparatus and the conventional apparatus in which the liquid supply pipe 6 to be separated and the separation liquid take-out section 8 shown in FIG. -From the viewpoint of the movement relationship with the separation liquid take-out part, it can be seen that the relative movement relationship is exactly the same. Therefore, also in this annular chromatography apparatus, the eluent flow and the flow of the packing material form a cross flow, and the liquid to be separated supplied above the packing material in the annular packing section 34 flows downward due to the flow of the eluent. Since the liquid supply pipe moves relatively perpendicular to the filler, each component in the liquid to be separated spirally flows due to affinity for the filler. As a result, a component having a high affinity for the filler elutes at a position distant from the liquid supply pipe to be separated, and a component having a low affinity elutes at a position near the supply port of the liquid supply pipe to be separated.

That is, in the annular chromatography apparatus of the above embodiment, first, the jacket portion 20 of the inner tube 14 and the jacket portion 27 of the outer tube 15 are kept constant by a refrigerant, a heating medium, and a thermostat if necessary. The discharged fluid or the like is circulated, and the annular filling portion 34 is maintained at a predetermined temperature.
When a coolant or a heat medium is allowed to flow through the jacket portions 20 and 27, for example, the outlet 68 and the outlet 68, which have little effect on the flow of the eluent, are used.
A thermometer is attached to the lower portion of the annular filling section 34 between the 68, and the temperature of the annular filling section 34 is controlled by controlling the supply amounts of the refrigerant and the heating medium to the jacket sections 20 and 27 based on the signal of the thermometer. Will be

When the raw material (separated liquid to be separated) whose temperature is adjusted by a heat exchanger or the like (not shown) is supplied from the raw material inlet pipe 60 to the raw material supply tube 37 as necessary, the raw material is supplied to the raw material supply tube 37. The inner circumference of the cylindrical portion 35 and the block 50
It flows into the space of the raw material inflow line formed between the outer periphery and the pair of upper and lower seal packings 52, 52. The rotating shaft 4
One end communicates with this space and the other end of the block 50 that rotates synchronously with the block 4 is a space formed between the upper part of the inner cylinder 14 of the block 50 and the upper lid 12. Is formed, the raw material flows into the raw material feed pipe 65 from the space via the raw material passage 62 which rotates for the first time. Therefore, while the raw material feed pipe 65 constituting the liquid to be separated supply pipe for supplying the liquid to be separated is buried in the upper filler of the circular filling part 34, the raw material feed pipe 65 is synchronized with the rotating shaft 44 and Therefore, the raw material is reliably supplied to the upper filler of the annular filling portion 34.

In an annular chromatography apparatus in which the annular filling section 34 is fixed as in this method, at least the liquid supply pipe to be separated has an annular filling section 34 at the tip.
It is necessary to supply the liquid to be separated while moving along the annular shape. The eluent supply pipe 74 for supplying the eluent (eluent) is provided in the annular filling portion 34 in this embodiment. The eluent is of a fixed type as in FIG.
Supplied to maintain a predetermined level of liquid at the top,
The eluent is uniformly dropped over the entire annular filling portion 34.

Further, a flow control valve (valve) is provided downstream of the outlet 68 for discharging the discharged liquid from the annular filling section 34.
69 is provided, by which the flow rate is adjusted so that the eluent further falls uniformly over the entire annular filling portion 34. That is, in order to equalize the flow rate of the eluent flowing down the packing material, the eluent is supplied to the upper portion of the annular packing portion 34 (the liquid to be separated has a smaller supply amount than the eluent and is almost It does not need to be supplied or not supplied),
The opening of the valve 69 is adjusted. For small devices, the outlet 6
Since the effluent from 8 drops dripping through the valve 69, the flow rate is adjusted by counting the number of drops per unit time and adjusting the opening of the valve 69 so that the number of drops is the same.
In order to increase the accuracy of a large-scale device and further improve the accuracy, a flow meter is provided downstream of the valve 69, and the opening of the valve 69 is adjusted by checking the value. In this case, depending on the liquid to be separated,
It is not necessary to attach a flow meter to all the outlets 68, and the flow rate does not change so much in the vicinity where the flow rate is measured even for each of a plurality of outlets, so that the flow rate is measured and the opening of the valve 69 is adjusted. The initial objective can be achieved by visually adjusting the degree of opening or the flow state. Also, a movable flow meter is prepared, and after measuring the flow rate at one outlet 68, the flow meter is removed, the flow meter is connected to the next outlet 68, and the valve 69 of the outlet 68 is The opening can also be adjusted.

The eluent containing the separation component flowing down from the outlet 68 via the valve 69 rotates in synchronization with the liquid supply pipe to be separated, and the relative position thereof is constantly maintained constant. Flows into the sorting container 77 on the receiving pan 75. The eluent-only liquid that does not contain a separation component and flows down from the outlet 68 through the valve 69 flows directly into the first receiving tray 75. The eluent containing the separation component flowing into the sorting container 77 is transferred to the component receiving container 80 formed of a predetermined annular groove of the second receiving tray 78 disposed below the first receiving tray 75, and then to the separating container 77. Through an extraction pipe 77a and an effluent introduction pipe 83 connected thereto.

According to this structure, the valve 69 is provided downstream of the outlet 68 for discharging the discharged liquid from the annular filling portion 34,
Since the flow rate is adjusted so that the eluent uniformly falls over the entire annular filling portion 34, the components to be separated can be efficiently separated. Further, in the conventional cyclic chromatography apparatus, the flow rate of the eluent flowing down into the packing material is low,
Separation takes time. Increasing the separation speed without reducing the separation efficiency requires finer filler particle size and higher eluent flow rates. However, an increase in the eluent flow rate causes an increase in the discharge pressure of the pump for supplying the eluent.

In the annular chromatography apparatus of the above embodiment, a block 50 that rotates synchronously with the rotary shaft 44 is inserted inside the cylindrical portion 35 of the raw material supply tube 37 to which the raw material inlet pipe 60 is connected. A pair of upper and lower seal packings 52 are interposed between the peripheral surface and the outer peripheral surface of the block 50 so as to prevent the raw material from leaking to the outside. A space is formed between the space 52 and the block 50, and one end thereof communicates with the block 50 that rotates synchronously with the rotation shaft 44, and the other end is connected to the upper portion of the inner cylinder 14 of the block 50 and the upper lid 12. A raw material passage 62 connected to the raw material feed pipe 65 is formed in a space formed between the raw material feed pipe 65 and the raw material inlet pipe 60 is hermetically sealed with the raw material feed pipe 65 that moves synchronously with the rotating shaft 44. Since the pressure-resistant seal structure to be through,
As a pump for supplying the eluent, a high-pressure pump can be used, and rapid separation can be performed.

If a mechanical seal is used instead of the seal packing 52, the pressure resistance of the structure above the annular filling portion can be further improved. FIG.
Is a flow sheet showing the overall flow in the case where the above-described embodiment apparatus of FIG. 1 is enlarged and used industrially. To explain this, the raw material (liquid to be separated) stored in the raw material tank 88 is supplied to the raw material pump 89.
Is supplied to the raw material feed section a of the annular chromatography apparatus A via a raw material supply line 92 provided with a flow control valve 90 and a flow meter 91. Eluent tank 93
The eluent stored therein is supplied by an eluent pump 94 to an eluent supply pipe b of an annular chromatography apparatus A via an eluent supply line 97 provided with a flow control valve 95 and a flow meter 96.

Below the tray c of the annular chromatography apparatus A, a product recovery unit 98 is provided instead of the second tray 78 and the component receiver 80 of the embodiment of FIG.
A plurality of partition walls 100 that are annularly continuous in the circumferential direction are provided concentrically inside the main body 99 of the product collection device 98, and two annular product receiving parts formed by the partition walls 100 are formed inside the main body 99. Containers 101 and 102 and one circular discharge / eluate collection container 103 are formed. The separated product A in the product receiver 101 for the product A is introduced into the product recovery tank 105 via the product recovery pump 104. Also, the product B in the product receiver 102 for the product B
Is connected to the product recovery tank 10 via the product recovery pump 106.
7 is introduced. Further, the discharged eluent in the discharged eluent recovery container 103 is introduced into a discharged eluent recovery tank 109 via a discharged eluent recovery pump 108.

A level controller 110 for controlling the level in the two product receivers 101 and 102 and the level in one discharge / eluent recovery container 103 is provided, and based on a level signal from the level controller 110. The pumps 104, 106, 108 are controlled and the product receiver 10 is controlled.
1, 102 and the discharged eluent recovery container 103 prevent the separated product or discharged eluent from overflowing.

In some cases, the collected eluate is appropriately purified as required and reused. Next, the effects of the cyclic chromatography apparatus according to the first embodiment of the present invention will be described with reference to experimental examples and comparative experimental examples by the present inventors. Experimental Example 1 Chromatography was performed on the following liquid to be separated under the following operating conditions using the following annular chromatography apparatus, the following packing material, and the following eluent, and the following results were obtained. Reached. [Circular Chromatography Apparatus] An apparatus similar to the apparatus shown in FIG. 1 and having the following configuration.

The double cylindrical portion forming the body has an outer cylinder inner diameter of 1
It is 60 mm, the outer diameter of the inner cylinder is 150 mm, and the height is 450 mm. At the outlet, the valve for adjusting the flow rate shown in FIG. 2 was provided. A 10-μm stainless sintered filter was provided at the lower end of the annular filling portion formed by the double cylindrical portion.

As for other materials, stainless steel materials were used except for packings. In order to evaluate the separation function, the effluent from each outlet (48 locations in the experimental device) was collected so that the components could be analyzed. That is, the sorting container on the first pan of the embodiment apparatus of FIG. 1 is removed,
Immediately below the 48 outlets of the first receiving pan, holding holes capable of holding a test tube (inner diameter 8 mm × length 40 mm) in an upright state were provided.

When a steady state was reached after the operation of the experimental apparatus started, a test tube was inserted into the holding hole, and about 1 to 2 ml of the effluent was simultaneously collected in all the test tubes. [Filler, eluent, liquid to be separated]-Filler Cation exchange resin Dowex 50W-X
8 Average particle size 0.14mm ・ Eluent 0.1M sodium citrate buffer (pH
3.4) ・ Liquid to be separated Aspartic acid and glycine aqueous solution (concentration
20 mol / m ³ each) [Operating conditions] The liquid to be separated is supplied from the supply pipe for the liquid to be separated, and the eluent is supplied from the supply pipe for the eluent.

The flow rate of the liquid to be separated is 0.6 cm ³ / mi.
n ・ Eluent (eluent) supply flow rate 6.0 cm ³ / min ・ Separate liquid supply pipe rotation speed 1.44 deg / min ・ Separate liquid supply pressure Gravity (0 kg / cm)
² G) [sample analysis] and analysis of aspartic acid and glycine solution was by the ninhydrin method (detector UV meter). [Results] FIG. 4 shows the relative concentrations of aspartic acid and glycine (each concentration in each effluent / each concentration in the liquid to be separated) of a sample collected in a test tube.

From these results, it can be seen that the peak shape is sharp, the overlap between the components is extremely small, and the separation of the two components is good. Comparative Experimental Example 1 An annular chromatography apparatus similar to that of Experimental Example 1, except that a pipe having an inner diameter of 1 mm was attached in place of the flow rate control valve at the outlet of Experimental Example 1, and the other conditions were the same as those of Experimental Example 1. Was exactly the same.

As shown in FIG. 5, both peak shapes were wide and overlapped, as shown in FIG. Experimental Example 2 Using the apparatus used in Experimental Example 1, the supply amount of the liquid to be separated and the supply amount of the eluent were increased and the opening of the flow control valve in the discharge section was adjusted as described below. A pressurization operation was performed at a higher supply pressure, and the separation accuracy, separation speed, and the like were compared with the results of Experimental Example 1.

The other fillers, eluents and liquids to be separated are exactly the same as in Experimental Example 1. [Operating conditions] ・ The liquid to be separated is supplied from the liquid supply pipe, and the eluent is supplied from the eluent supply pipe. - the separated liquid supply flow rate 4.5 cm ³ / min · eluent (eluent) feed flow rate 45.0cm ³ / min · separation target liquid supply pipe rotation speed 1.44deg / min · separation target liquid supply pressure 0.1 kg / cm ² G [Results] Aspartic acid and glycine were extracted with the concentration distribution shown in FIG.

From this result, even if the processing speed (liquid supply flow rate of the liquid to be separated) is increased to 7.5 times as compared with the experimental example 1, the peak shape is slightly widened, the overlap is slightly generated, and the separation accuracy is slightly lowered. However, it turns out that separation can be performed without any problem. Therefore, it can be seen that when this high-pressure cyclic chromatography method is employed, a large amount of raw materials can be treated with a small apparatus.
To further increase the separation accuracy from the above results,
Usually, the filler particle size may be reduced.

FIG. 7 is a perspective sectional view showing an embodiment of the second invention. That is, in this figure, in this embodiment, instead of the valve 69 provided in the outlet 68 in the embodiment of the first invention in FIG. 1, the flow rate is automatically controlled based on the flow rate measurement value. A flow control device 111 is provided, and the other components are the same as those in FIG.

FIG. 8 shows the configuration of the flow control device 111, and FIG. 9 is an explanatory diagram of its operation. That is, the flow control device 111 includes the flow indicator 112 and the flow setting valve 1.
13 and a flow control valve 114. The flow indicator 112 is formed in one tube portion 115a of the inverted U-shaped tube 115. The opening of one of the tube portions 115a of the inverted U-shaped tube 115 is formed as an inflow port a, and the pipe 211 is screwed into the female thread portion 13a of the pedestal 13 downstream of the outflow port 68.
Connected to The pipe 211 has a union 2
11a is interposed so that the screw fitting can be easily performed. An outlet b is formed in the opening of the other pipe 115b, and the flow setting valve 113 is connected to the outlet b. This flow setting valve 11
Reference numeral 3 includes a main body 113a, a valve body 113b disposed in the main body 113a, and an operation section 113c of the valve body 113b. An inflow port c connected to the outflow port b is formed around the flow rate setting valve body 113a, and an outflow port d is formed at the bottom. The valve element 113b adjusts the flow area by adjusting the opening area of the outlet d.
Penetrates the upper wall of the main body 113a and protrudes to the outside, and the operating portion 113c is formed at the protruding end.

On the other hand, the flow control valve 114 is
4a and a diaphragm 11 disposed in the main body 114a
4b and the valve element 11 connected to the diaphragm 114b
4c, a spring 114d for elastically urging the diaphragm 114b upward, and a flow pipe 114e whose passage opening area is adjusted by the valve element 114c. One end of the flow pipe 114e is connected to the flow rate setting valve 11
The other end is formed as an outlet e, and is connected to a pipe 214 that opens toward the sorting container 77 or the first tray 75. Flow control valve body 1
Inside 14a, two chambers A and B are provided by a diaphragm 114b.
The partition is formed. One chamber A communicates with the inside of the main body 113a of the flow rate setting valve 113 via a pressure guiding pipe 115, and the other chamber B communicates with the flow pipe 11 via a pressure guiding pipe 116.
4e. The spring 114d is interposed between the outer surface of the upper wall of the main body 114a and the locking portion 114f provided at the upper end of the valve body 114c protruding from the upper part of the main body 114a, and raises the diaphragm 114b upward as described above. Elastic biasing.

In the flow rate control device 111 having such a configuration, when the flow rate Q increases, the contraction portion C of the flow rate setting valve 113
The differential pressure before and after (P ₁ −P ₂ ) increases. Pressure P ₁ , P
₂ is connected to the diaphragm 11 by the pressure guiding tubes 115 and 116.
4b, the diaphragm 114b generates a downward force against the elastic force of the spring 114d, and the valve body 114c of the flow control valve 114 moves downward to decrease the flow rate Q.

When the above state is stabilized, the following equation is established. (P ₁ −P ₂ ) × S = FW where S 但 し Effective pressure receiving area of diaphragm F─ Upward force by spring W─ Weight of control valve in fluid When the above equation is modified, the following equation is obtained. .

P ₁ -P ₂ = (FW) / S As described above, the pressure difference before and after the contraction portion C of the flow rate setting valve 113 is always kept constant, and a constant flow rate can be obtained. Therefore, as shown in FIGS. 7 and 8, by providing the flow control device 111 having such a configuration at each of all the outlets 68 of the annular chromatography device, by adjusting each of the flow setting valves 113, the inside of the filler is reduced. The flow rate of the eluent (including the liquid to be separated) flowing down can be kept uniform without being disturbed over the entire circumference of the annular filling portion 34, and each component in the liquid to be separated is
The components can flow in a fixed spiral, and the outflow position of each component does not fluctuate, so that efficient component recovery can be performed.

FIG. 10 shows a second embodiment which is an application of the second invention. In this embodiment, instead of the tray 75 supported on the rotating shaft 44 and rotating in synchronization with the raw material feed pipe 65, at least the number of target components (to be obtained) +1 (elution) is provided below the outlet 68. In addition to the provision of the annular discharge channel 117 for the liquid), all the outlets 68 at the lower end of the annular filling portion 34 are connected to the respective outlets 68, and the respective outlet pipes 118 provided with the flow rate control device 111 are connected to the respective outlet pipes 118. A branch is made downstream of the flow control device 111 and an automatic switching valve 1 is connected to each of the annular discharge passages 117.
Valve switching control means for controlling the automatic switching valve 119 so as to always select a predetermined annular discharge passage 117 in accordance with the annular movement position of the liquid supply pipe to be separated (see FIG. This has the advantage that there is no rotating object such as the tray 75 and airtightness can be maintained.

The annular discharge channel 117 may not be completely annular. For example, a pipe whose both ends are closed may be formed into an arc shape, and the pipe may have an outlet pipe 118 from the total outlet 68.
It is only necessary that a pipe be provided for communicating with the product receiver 84 while communicating with the product via the automatic switching valve 119. The number of the annular discharge channels 117 is, for example, A, B,
When the three components of C are functionally separable, usually 3 + 1
(For the eluent), but if only the component A is to be separated, the number of the annular discharge channels 117 may be two. A plurality of annular discharge channels 117 corresponding to the eluent may be provided.

In the above-described annular chromatography apparatus, each of the automatic switching valves 11 corresponds to the apparent lateral (circumferential) movement of each component at the lower end of the annular packing portion 34.
9 is switched to an annular discharge channel 117 corresponding to each component.
(There is also a circular discharge channel for only the eluent). For example, at the outlet 68 from which the component A has moved so that only the component A flows into the predetermined annular discharge channel 117 in response to the movement of the component A, the annular discharge channel 11 for collecting the component A is used.
The automatic switching valve 119 leading to 7 is opened for a certain period of time, and the other automatic switching valve 119 of the outlet 68 is closed.

Here, FIG. 11 and Table 1 are explanatory diagrams of the operation of the above-described selection mechanism of the annular discharge channel 117.

[0066]

[Table 1]

In the annular chromatography apparatus shown in FIG. 10, dozens of outlets are usually provided, but FIG. 11 shows a case in which eight outlets are provided for simplicity of explanation. Are developed in a plane.
In Figure 11, A ₁ to A ₈ is an automatic switching valve for product A recovery, B ₁ .about.B ₈ automatic switching valve for product B recovered, C ₁ -C
₈ is an automatic switching valve for the discharge eluent.

Now, the open / close state of the automatic switching valve in the state of FIG.
The open position of the automatic switching valve in the range of 110 ° to 160 ° from the raw material feed section and the automatic switching valve for recovering the product B are set to the automatic switching valve in the range of 220 ° to 310 ° from the raw material feed section, and for the discharge eluent. The open position of the automatic switching valve of
It is necessary to open the automatic switching valve where the automatic switching valve for recovering B is closed. Specifically, the automatic switching valve for collecting the product A is opened at A ₄ , and closed at A _1, A _2,
A _3, A _5, A ₆ , A ₇ , A ₈ , B ₆ , B ₇ , and B _1, B _2, B _3, B ₄ , B ₆ , B ₇ , and B ₁
Opening of the automatic switching valve for B _5, B ₈ , discharge eluent is C _1, C
_2, C _3, C _5, C ₈ , closed are C ₄ , C _6, C ₇ .

The position of the outlet 68 from which each component flows out is a position shifted by a predetermined phase from the position of the raw material feed pipe 65 constituting the liquid supply pipe to be separated, and the position of the phase shift depends on various conditions of chromatography. Different, determined by experiment. The same operation timing (moving speed of the component A) from the outlet 68 to the next adjacent outlet 68 is equivalent to that of the raw material feed pipe 65 if the chromatography conditions such as the supply amount of the eluent are constant. The specific annular discharge flow path 117 is always selected at a predetermined position apart from the moving raw material feed pipe 65, which is the same as the peripheral velocity, based on the moving raw material feed pipe 65.

As shown in FIG. 10, the timing of selecting the specific annular discharge channel 117 is determined by the plurality of proximity sensors 120 provided on the inner peripheral surface of the gantry 13 and the raw material feed pipe 65 at the lower end of the rotating shaft 44. The positioning bar 121 attached at the same angle can be set in synchronization with the rotation of the rotation shaft 44 (the rotation position of the raw material feed pipe 65).

As shown in FIG. 12, the valve switching control means of this embodiment comprises a plurality of proximity sensors 120,
A positioning bar 121 and a control device 122 for outputting an open / close signal to a predetermined automatic switching valve 119 based on an approach signal of the positioning bar 121 output from each proximity sensor 120
(Sequencer, programmable controller or personal computer).

That is, as shown in FIG. 11 and Table 1, the angle between the raw material feed pipe 65 and the outflow position of each component of the liquid to be separated is always constant. And
The liquid supply pipe position confirmation means 123 in FIG. 12 confirms the position of the raw material feed pipe 65 based on the signal of the proximity sensor 120, and the automatic switching valve opening / closing timing setting means 124.
Is controlled so that the automatic switching valve 119 at a predetermined angular position with respect to the position of the raw material feed pipe 65 always selects a predetermined annular discharge flow path 117. Table 1 shows a specific example. The automatic switching valve is controlled as shown in FIG.

In Table 1, when, for example, the proximity sensor S-1 is turned on, the automatic switching valve 119 which is opened includes A ₄ , B
_{6, B 7, C 1,} C 2, C 3, C 5, a C _8. It is not necessary to measure the position of the raw material feed pipe 65 directly, but only indirectly.
It is not necessary that the position of the raw material feed pipe 65 exactly coincides with the position of the raw material feed pipe 65.

Therefore, the positioning bar 121 need only be fixed to the rotating shaft 44, and the positioning bar 1
It is sufficient that the automatic switching valve 119 always selects the predetermined annular discharge channel 117 corresponding to the position 21. Further, in the above embodiment, the outflow pipe 118 is connected to each of the annular discharge passages 11.
7 and an automatic switching valve 119 is provided in each of the branched annular discharge passages 117.
18 is provided with a multi-way valve, and from the multi-way valve,
As a device provided with a branch pipe leading to 7, the number of valves used may be reduced.

Further, the following configuration may be adopted as the valve switching control means. That is, since the moving speed of the raw material feed pipe 65 is constant, each automatic switching valve 1
The operation of No. 19 repeats the same operation periodically corresponding to the position of the raw material feed pipe 65. Therefore, if the phase shift of the cycle of each automatic switching valve 119 is determined in advance according to the position of the raw material feed pipe 65 at the time of starting, by providing a timer for each automatic switching valve 119 instead of the proximity sensor 120, each automatic switching valve 119 can be provided. The switching valve 119 can be controlled.

For example, valve switching control means as shown in FIG. 13 can be considered. In this valve switching control means, the position of the raw material feed pipe 65 before the start is, for example, the “rotation angle from the reference position” or the “number of the automatic switching valve 119 located immediately below the raw material feed pipe 65”. When input to the input means 125, the automatic switching valve 119 based on the information is set so that the automatic switching valve 119 closest to the raw material feed pipe 65 corresponds to the valve number 1 in Table 2.
Sends a correction signal to the automatic switching valve opening / closing timing setting means 127. Start switch 128
When the start signal is input from the CPU, the setting completion determination unit 129
Confirms that the correction signal has been output, and
Start 0. Automatic switching valve opening / closing timing setting means 12
7 receives the correction signal and outputs an open / close signal to each automatic switching valve 119 based on the time signal of the timer 130 as shown in Table 2.

[0077]

[Table 2]

Although the respective embodiments have been described above, in the embodiment of FIG. 1 which is the first invention, the raw material feed pipe 65 and the like constituting the liquid supply pipe to be separated and the separating liquid as the separation liquid take-out section are provided. The example in which the first invention is applied to a system in which the container 77 rotates and the annular filling portion 34 in which the packing material is annularly filled is fixed, that is, a so-called fixed annular chromatography device has been described. The first invention can also be applied to a system in which the eluent supply pipe and the fractionation container are fixed and the annular packing section is rotated, that is, a so-called rotary annular chromatography apparatus.

In the embodiment of the first invention, the valve 69 is provided directly at the outlet 68. However, the present invention is not limited to this, and an outlet pipe (tube) is attached to the outlet 68, and the outlet pipe is connected to the outlet pipe. A valve may be provided. Further, in the embodiment of the first invention, the unnecessary eluent at the outlet 68 is not received by the sorting container 77, but directly flows into the first tray, and the container portion of the second tray 78 via the pipe 86. However, the unnecessary eluent may be received in the collection container 77 and flown into the container portion 85 of the second receiving tray 78 via the effluent introduction pipe 83.

In the second embodiment of the present invention, an example of a very small flow control device 111 is shown as a flow control device. However, the present invention is not limited to this. May be a flow control device including the flow control valve 90 (95) and the flow meter 91 (96) in FIG. Further, in each embodiment of the first and second inventions, the annular filling portion 34 is constituted by a double cylindrical portion of a circular inner cylinder and an outer cylinder, but is not limited to a circular shape, and may be a truncated cone or an ellipse. well. In short, any shape may be used as long as it is annular.

Although the raw material feed pipe 65 as the liquid supply pipe to be separated is buried inside the annular filling portion 34, the invention is not particularly limited to this. For example, a glass bead layer may be provided on the upper portion of the annular filling portion 34, and the liquid supply pipe to be separated may be buried there. Also, if a vertical partition for partitioning the annular filling portion 34 in the radial direction is provided. Alternatively, the liquid to be separated may be supplied from above the annular filling section 34.

Further, in each embodiment of the first and second aspects of the present invention, the supply pipes are provided for the eluent and the liquid to be separated.
Although the example in which the book is provided has been described, the supply pipe may be two or more. In other words, several types of eluents used in a normal batch system are sequentially switched and eluted in several stages,
A gradient (gradient) elution method, which aims to shorten the elution time and sharpen the peak shape, is to elute a step (step) elution method for accelerating the elution or gradually and continuously changing the composition. As is known from JP-A-2-189458 and JP-A-4-227820, in an annular chromatographic apparatus, a plurality of eluent supply pipes are provided, and the composition of the eluent supplied from the eluent supply pipe is determined. This can be done by changing each supply pipe. That is, in the annular chromatography in which the annular filling section 4 shown in FIG. 15 rotates in the circumferential direction, the eluent supplied from several eluent supply pipes can be changed for each supply pipe. In addition, in the annular chromatography of the above-described experimental example in which the liquid supply pipe rotates and the annular filling section rotates, as shown in FIG. This can be performed by changing the eluent to be supplied from several eluent supply pipes 132 moving along the circumferential direction of each 131 for each supply pipe 132.

Since gradient elution changes the composition of the eluent continuously, for example, in the case of a two-component eluent, the supply amount of one eluent is sequentially increased from a plurality of eluent supply tubes. By doing so, the eluent composition was changed approximately continuously (linearly). If the number of eluent supply tubes is infinitely large, a completely linear change occurs. In the step elution, since the eluent composition is changed stepwise, it can be realized by changing the supply amount of the other eluent stepwise from a limited plurality of eluent supply pipes.

Therefore, in an annular chromatography apparatus in which the annular filling portion is fixed, at least the liquid supply pipe to be separated should be separated while its tip moves along the annular shape of the annular filling portion. The liquid to be separated must be supplied, but the eluent supply pipe differs depending on various chromatographic methods. For example, as in the present embodiment, the eluent is supplied at a predetermined level to the upper part of the annular packing portion. In the case where the eluent is supplied in a certain manner so that the eluent uniformly falls throughout the annular packing portion, it may be fixed as in the case of the annular packing portion. It may be necessary to supply the eluent while moving along the ring of the annular packing.

In order to effectively perform the step elution method and the gradient elution method, refer to Japanese Patent Application Laid-Open No. Hei 4-22782.
As disclosed in Japanese Patent Publication No. 0, a vertical partition may be provided to partition the annular filling portion in the radial direction. Further, the cyclic chromatography apparatus according to the present invention can be provided by the ion exchange chromatography, size exclusion chromatography, partition chromatography, adsorption chromatography, optical resolution chromatography, hydroxyapatite chromatography, and affinity chromatography described in the conventional examples. Of course, it can be applied to night chromatography and the like.

As described above, the present invention has been described with reference to the specific embodiments. However, the present invention is not limited to these embodiments, and is attached to the present invention by a person skilled in the art. It should be noted that various changes and modifications can be made without departing from the scope of the claims.

[0087]

As described above, according to the first aspect of the present invention, there is provided an annular filling portion in which a filler is annularly filled, and an outlet for discharging a liquid discharged from the annular filling portion. In an annular chromatography apparatus in which an agent supply pipe and a liquid to be separated are provided above the annular packing portion, valves are provided at all the outlets or at pipes attached to the outlets, and the eluent is provided by the valves. The components to be separated can be efficiently separated by adjusting the flow rate so that the water drops uniformly over the entire annular filling portion.

According to the second aspect of the present invention, there is provided the annular filling portion filled with the filler in an annular shape, and the outlet for taking out the discharged liquid from the annular filling portion. tube and it said provided an annular packing unit the separated liquid supply pipe supplying a separated liquid to be separated while moving along the circular to the annular packing unit top or fluid to all of the outlet
A flow control device is provided in a pipe attached to the outlet, and by adjusting the set values of all the flow control devices, the flow rate of the eluent (including the liquid to be separated) flowing down into the packing material can be reduced throughout the annular packing portion. Over the circumference, it can be kept uniform without disturbing,
Each component in the liquid to be separated can flow in a fixed spiral, and the outflow position of each component does not fluctuate, and can be efficiently recovered.

[Brief description of the drawings]

FIG. 1 is a perspective sectional view showing an embodiment of the first invention.

FIG. 2 is a diagram showing a configuration of a valve in the embodiment.
(A) is a sectional front view, and (B) is a plan view of a dish-shaped portion.

FIG. 3 is a flow sheet showing the entire flow when the apparatus of the embodiment of FIG. 1 is enlarged and used industrially.

FIG. 4 is a diagram showing the results of Experimental Example 1 using one embodiment of the first invention.

FIG. 5 is a diagram showing a result of a comparative experimental example.

FIG. 6 is a diagram showing the results of Experimental Example 2 using one embodiment of the first invention.

FIG. 7 is a perspective sectional view showing one embodiment of the second invention.

FIG. 8 is a front view showing the configuration of the flow control device in the embodiment.

FIG. 9 is an explanatory view of the operation of the above flow control device.

FIG. 10 is a perspective sectional view showing another embodiment of the second invention.

FIG. 11 is an explanatory view of the operation of the annular discharge channel selection mechanism of the embodiment.

FIG. 12 is a diagram showing a configuration of a valve switching control unit of the embodiment.

FIG. 13 is a diagram showing a configuration of another valve switching control means of the embodiment.

FIG. 14 is a schematic explanatory view of still another embodiment.

FIG. 15 is a schematic explanatory diagram of a conventional annular chromatography device.

[Explanation of symbols]

 Reference Signs List 10 annular chromatography apparatus main body 34 annular packing section 62 raw material passage 65 raw material feed pipe 68 outlet 69 valve 74 eluent supply pipe 77 preparative container 111 flow control device

Claims (2)

(57) [Claims] 1. An annular filler filled with a filler in an annular shape,
An eluent supply pipe that is provided at the lower end of the annular filling portion and that draws out the discharged liquid from the annular filling portion, and that supplies an eluent to at least the annular filling portion; And a liquid supply pipe for supplying the liquid to be separated is provided at the upper part of the annular packing portion .
An annular chromatography apparatus characterized in that a valve is provided in a closed tube . 2. An annular filling portion filled with an annular filler,
An eluent supply pipe provided at the lower end of the annular filling part, for discharging the liquid discharged from the annular filling part, and fixing the annular filling part and supplying at least an eluent to the annular filling part When, the separation target liquid supply pipe supplying a separated liquid to be separated while moving along the circular of the annular packing portion is provided on the annular packing unit top, all of the outlet
Alternatively , an annular chromatography apparatus , wherein a flow control device is provided in a tube attached to the outlet .