JPH054012U - Continuous treatment type liquid chromatograph - Google Patents

Abstract

(57) [Summary] [Structure] Three or more columns are arranged in parallel, and the columns are rotated by a predetermined angle to successively supply the liquid to be treated or the eluent to the upper part of each column. Liquid chromatograph system. [Effect] Since parallel and continuous processing is performed, the ratio of the processing amount / equipment volume can be increased, the processing efficiency can be increased, and a large amount of separation can be achieved.
Purification is possible.

Description

[Detailed description of the device]

[0001]

[Industrial applications]

  The present invention relates to a liquid chromatograph device.

[0002]

[Prior art]

  The conventional liquid chromatograph used for separation and purification of substances is a single column. It is common to use an adsorbent and an eluate by alternately flowing the liquid to be treated and the separated liquid. Is.

[0003]

[Problems to be solved by the device]

  However, such a conventional liquid chromatograph apparatus uses a column. Therefore, it is necessary to alternately flow the liquid to be treated and the eluent. Therefore, in processing operations There is a complete break, and the liquid cannot be processed continuously. Therefore, the efficiency becomes poor. Also When the column is made larger to handle a large amount, the liquid becomes uniform in the radial direction inside the column. It is difficult to disperse and distribute the components in the water, and usually the separation of each component becomes poor. Therefore, This method also has a problem that it is difficult to process a large amount.

[0004]   In addition, the column is shaped like an inverted Y with the lower part branched into two, and the upper stationary phase is retained. It has been proposed to divide into two stationary phases filled with fillers having different holding powers (special (Kaihei 2-236162) basically uses the above single ordinary column. It has the same drawbacks as the ones.

[0005]   Further, in Japanese Patent Laid-Open No. 1-68656, a mobile phase inlet, a first inlet, is provided on the downstream side of the sample inlet. A component extraction port, a desorbed liquid injection port, and a second component extraction port are provided at predetermined intervals A countercurrent liquid that improves continuous throughput by moving the mobile phase countercurrently. Although a chromatographic device is disclosed, the mobile phase liquid and the desorbed liquid are used in an annular container. Therefore, the liquids are mixed with each other, and the separation performance is deteriorated when operating for a long time.

[0006]

[Means for Solving the Problems]

  The present invention has been made in view of the above circumstances, and three or more columns are arranged in parallel. Arrange them in rows and rotate them by a specified angle to place the liquid to be treated or the eluent on top of each column. Continuous processing type liquid chromatograph device characterized in that Is provided.

[0007]   According to the continuous processing type liquid chromatograph device of the present invention, the liquid is discharged from each column. Components are collected and collected from the column at the position determined by the retention time, Can be discarded and removed.   Here, the position of the column from which the component A is discharged is obtained as follows.     Angle (position) from the raw material supply port of the column from which component A is discharged     = Retention time of component A (min) x rotation speed of switching valve (deg / min)

[0008]

【Example】

  Next, the present invention will be described with reference to one embodiment shown in FIG. It is a schematic diagram of one example of a tograph apparatus.   In the figure, 1 is a column packed with a packing material for separation, and a column having three or more columns is formed. They are arranged in parallel. 2 is a rotary switching valve for the liquid to be treated introduced into this column. From now on, each line 3 is connected to the upper part of each column 1. Four Is a line connected to this rotary switching valve, and is the liquid to be treated from the tank 5 after being treated. Is introduced into the column through valve 2 via pulseless pump 6 and degasser 7. one Direction 8 is a liquid extraction line from the column 1. 9 is an eluent tank, which is The rotary switching valve 2 is connected by a line 12 having a pulsating pump 10 and a deaerator 11. Street column 1 is introduced.

[0009]   Incidentally, 13 is a waste liquid tank, and 14 is a product tank containing a desired fraction.   In the present invention, the column 1 is a circular plane, preferably 100 to 3, more preferably. Typically, 60 to 10 pieces are provided in a cylindrical shape.   In order to use the device of the present invention, as described above, a large number of columns of three or more (n columns) is used. ) Is used and the liquid to be treated is continuously supplied, but the development (division) time is 1 cycle (T minutes). ), The column part is rotated by a predetermined angle every n times (T / n minutes). Supply the liquid to be treated to each column in turn and flow the developing liquid (eluent) at other times. You It is the development time when the necessary components come out after supplying the required components. The products are sequentially collected in the product tank 14.

[0010]   In this case, the column is arranged in a cylindrical shape, and the column must be rotated once for a certain time (T minutes). Make sure that the column for the development time at which the necessary components appear is at a fixed position.   In the present invention, it is preferable to switch the liquid to be treated and the developing liquid under pressure. As the switching valve of the above 1, a grooved presser disk and a stator with a supply port and a discharge port are installed. It is possible to use a switching valve having, for example, the one shown in FIG. 2 (A) is switched FIG. 2 (B) is a sectional view of a bottom surface of the valve holding disk. The switching valve 20 in the figure is a presser circle It consists of a board 21 and a stator 22. Reference numeral 23 is a circular groove through which the processed material passes, and 24 is an introduction groove. , 25, 25, 25 ... are provided on the entire circumference of 30 and are provided to the column after being processed. It is a mouthpiece. Reference numeral 26 is a supply port for the raw material of the liquid to be treated, and 27 is a supply port for the eluent. . Reference numeral 28 is a void portion through which the eluent passes, and the hatched portion in FIG. The part that contacts 2 is shown.

[0011]   The flow path of the liquid will be described with reference to FIG. 2. The liquid supplied from the raw material supply port 26 has a circular shape. Flowing through the groove 23 in the direction of the arrow a, from the introduction groove 24, the It flows into the supply port 25a and is supplied to the column below it. The dashed arrow C indicates the route Show. The eluent is supplied from the supply port 27, and the voids 28 are radially formed in the direction of arrow b. Flow into the column supply ports 25b, 25b, 25b, ... Supplied at the same time. In Figure 2, the lower part of the switching valve and the piping to the column rotate at the same speed, Fix the mouth of the recovery tank (eluent tank) at the position determined by the retention time. If so, the target product is recovered.

[0012]   Note that FIG. 3 shows another example of the switching valve, in which the supply of the raw material and the supply of the eluent are performed below the switching valve. 29 is an inlet for the liquid to be treated and 30 is an inlet for the eluent. is there. The other points are the same as those in FIG. 2, and the same reference numerals as those in FIG. 2 indicate the same things. That machine The structure is the same as in FIG. 2 except that the liquid is supplied from below. Raw material in this embodiment , The piping for the eluent switching valve and the piping for supplying the column are gathered at the bottom. Can be fixed. In this way, the upper part is rotated at a constant speed and the The liquid discharged from the column at the position determined by the recovery time is collected in order.   Next, an example of using the device of the present invention will be shown.

[0013] Reference example 1   A liquid chromatographic bluff device having 30 columns as shown in FIGS. 1 and 2 is used. In the meantime, the following separation and purification were performed.   Impurity with desensitizing action in ethyl acetate solution after reaction of magenta coupler A Remove X (about 0.3% / vs A). A silica-based stationary phase is packed in the column and the eluent is used. As a mixture of methanol: water 9: 1 (volume ratio) (containing 0.2% of pH adjusting liquid) ) Was placed in the eluent tank.

[0014]   While rotating the column once for 30 minutes, add 100% ethyl acetate solution of A (20%). Impurity X was the raw material when the eluent was also flowed at 100 cc / min. It was discharged from the 8th and 9th columns counting from the column immediately below the supply port. Also other A small amount of impurities was also discharged from the first, fourth, 24th, and 30th lines. Purified The coupler A was recovered from the 15th, 16th and 17th lines and removed as an impurity X. Well The recovery rate was 99% or more.   This operation was performed continuously for 24 hours, but even at the end, more than 99% of couplers were recovered. It was

[0015] Reference example 2   Using an apparatus similar to that used in Reference Example 1, the cyan color material B was dissolved in ethyl acetate after the reaction. Impurity Y (about 0.5% / B) having a fog generating action in the liquid is removed. silica The stationary phase of the system was packed in a column and methanol: water (4: 1) was used as an eluent. I put it in the link.

[0016]   An ethyl acetate solution (15%) of cyan colorant B was flowed at a flow rate of 150 cc / min to dissolve. The syneresis was also made to flow at 150 cc / min. Impurity Y was discharged from the 7th and 8th lines. So Other impurities are also removed from the 1st, 2nd, 5th, 10th, 15th, and 25th I put it out.   The purified color material B is recovered from the 19th, 20th and 21st lines, and the impurity Y is Was removed. The recovery rate was 99%.   This operation was carried out continuously for 8 hours, but it was stably purified.

[0017]

[Effect of device]

  According to the present invention, the rotation switching valve is rotated to sequentially introduce the column into which the liquid to be treated is introduced. Because of the switching, the elution process can be performed in sequence, and because the continuous process is performed, the steps before and after are performed. The entire purification, separation or synthesis system including can be processed continuously. Processed here Since a specific component in the liquid has a specific retention time, it must be associated with a specific position. , This component can be recovered.   In addition, the processing efficiency / equipment volume ratio can be increased by performing parallel and continuous processing, and processing efficiency Therefore, a large amount of separation and purification becomes possible. According to the device of the present invention, , Continuous separation and purification of useful photographic reagents (couplers, dyes, color image stabilizers, etc.), pharmaceuticals It is suitable for continuous refining of the above, continuous refining of printing color materials, and the like.

[Brief description of drawings]

FIG. 1 is a schematic view of an embodiment of a liquid chromatograph device of the present invention.

FIG. 2 shows an embodiment of a switching valve used in the present invention,
(A) is a bottom view of the presser disc of the switching valve, and (B) is a sectional view of the switching valve.

3A and 3B show another example of the switching valve, FIG. 3A is a bottom view of a holding disk of the switching valve, and FIG. 3B is a sectional view of the switching valve.

[Explanation of symbols]

1 column 2 rotary switching valve 3, 4 lines 5 Liquid to be treated tank 8 take-out line 9 Eluent tank

Claims (3)

[Scope of utility model registration request] 1. Arrangement of three or more columns in parallel,
A continuous treatment type liquid chromatograph device characterized in that the liquid to be treated or the eluent is sequentially supplied to the upper part of each column by rotating the column by a predetermined angle. 2. A continuous processing type liquid chromatograph device which collects a target component from a column located at a position corresponding to a retention time and separates an unnecessary component. 3. The continuous processing type liquid chromatograph apparatus according to claim 1, wherein a rotary switching valve is used.