JP5060400B2 - Chromatographic separation device - Google Patents

Description

  The present invention relates to a chromatographic separation apparatus.

  Conventionally, a method of separating (chromatographic separation) a plurality of components in a liquid by a chromatographic technique has been used industrially. In the chromatographic separation, a solid adsorbent is used, and components in the raw material liquid are separated by utilizing the difference in adsorption characteristics with respect to the adsorbent. The principle of chromatographic separation is that a raw material liquid containing two or more components to be separated is supplied to a packed bed packed with an adsorbent, and this raw material liquid is caused to flow down with an eluent such as water, whereby each of the above components is separated. Due to the difference in the adsorptivity with respect to the adsorbent, the weakly adsorbing component flows down relatively quickly, and the strongly adsorbing component flows down relatively slowly, so that the fraction containing each component is separated.

  Examples of chromatographic separation methods include a fixed bed method, a moving bed method, and a simulated moving bed method. In the simulated moving bed system, among the two or more components contained in the raw material liquid, a plurality of unit packed towers packed with an adsorbent having a selective adsorption capacity for a specific component are connected in series, and the most downstream portion By connecting the unit packed column and the unit packed column in the most upstream part, the raw material liquid and the eluent are passed through the endless circulation system for separation. In the simulated moving bed method, a fraction containing a component that moves fast in the circulation system (non-adsorbate fraction) and a fraction containing a component that moves slowly in the circulation system (adsorbate fraction) Extract from different positions and move sequentially downstream in the circulation direction of the circulation system while maintaining a fixed positional relationship between the raw material supply position, eluent supply position, non-adsorbate fraction extraction position, and adsorbate fraction extraction position. By doing so, it is well known that the apparatus realizes the processing operation of the moving layer in a pseudo manner.

  In addition, a method for performing step by step of extracting one component to separate three or more components and a step of extracting remaining components, such as a method of supplying raw material liquid and eluent, and fractions of each component Many methods for improving the chromatographic separation method of the pseudo moving bed method for switching the extraction position have been proposed (for example, Patent Document 1).

  Further, by connecting a plurality of unit packed towers in series, and connecting the most downstream unit packed tower and the most upstream unit packed tower to the endless circulation system, There has also been proposed a method of separating each component in the supplied raw material liquid while circulating the liquid in the circulation system without changing the supply position of the eluent and the extraction position of each component (for example, Patent Document 2).

  These methods are in principle common as a chromatographic separation method with the batch method in which the raw material liquid and the eluent are supplied to one end of the circulation system and the liquid is discharged from the other end. However, it is different in that the liquid in the circulatory system is passed through the unit packed tower connected endlessly, and it is possible to collect components with high productivity, high concentration and high purity which are industrially important. Therefore, it is superior to the batch method.

  When a highly viscous raw material liquid is supplied to a chromatographic separation apparatus constituted by such endlessly connected unit packed towers, an excessive pressure loss occurs in some of the unit packed towers. . In addition, the differential pressure in the unit packed column may increase due to deterioration of the adsorbent due to contact with the raw material liquid or the like. In addition, due to swelling and shrinkage due to differential pressure or osmotic pressure, the adsorbent is damaged, the packed bed is clogged, and this further increases the differential pressure. In general, the packed bed in the chromatographic separation apparatus can improve the separation performance by increasing the flow distance. On the other hand, if the flow distance of the packed bed is increased, the differential pressure increases. Under such circumstances, there is a problem that it is necessary to operate at a lower flow rate in order to reduce the pressure loss.

As means for solving the above problems, a method of increasing the average particle size of the adsorbent packed in some unit packed towers (for example, Patent Document 3) and a method using an ion exchange resin having a high degree of crosslinking as the adsorbent have been proposed. (For example, Patent Document 4).
Japanese Patent Publication No. 7-24724 JP 55-61903 A JP 2001-70704 A JP 2002-143605 A

However, since the techniques of Patent Document 3 and Patent Document 4 require a plurality of types of adsorbents, there is a problem that management becomes complicated for the user of the chromatographic separation apparatus. In addition, when an adsorbent having a large average particle size is used, or when an ion exchange resin with a high degree of crosslinking is used when the adsorbent is an ion exchange resin, there is a problem that the separation performance of the chromatographic separation apparatus is deteriorated. .
Therefore, the present invention is directed to a chromatographic separation apparatus that can reduce the influence of pressure loss. Another object of the present invention is to provide a chromatographic separation apparatus in which the separation performance does not deteriorate and maintenance is easy while reducing the influence of pressure loss.

The chromatographic separation apparatus of the present invention is filled with an adsorbent and forms packed layers having different channel lengths of the raw material liquid and the eluent and / or cross-sectional areas perpendicular to the flow direction of the raw material liquid and the eluent. A plurality of unit packed towers connected in series, and having a circulation system configured to circulate the raw material liquid and the eluent passed through the unit packed tower , and the circulation system has substantially the same volume. It is characterized by comprising a unit packed tower in which a packed bed is formed .

Furthermore , the unit packed tower to which the raw material liquid is supplied has a packed bed in which the flow path length of the raw material liquid and the eluent is shorter than the other unit packed towers constituting the circulation system, and / or the raw material liquid and the eluent It is preferable that the unit packed column has a packed bed having a large cross-sectional area perpendicular to the liquid passing direction.

  According to the chromatographic separation apparatus of the present invention, the influence of pressure loss can be reduced. Furthermore, the chromatographic separation apparatus of the present invention reduces the influence of pressure loss, does not deteriorate the separation performance, and is easy to maintain.

An example of an embodiment of the present invention will be described with reference to FIG. 1, but the present invention is not limited to the following embodiment.
FIG. 1 is a schematic diagram of a chromatographic separation apparatus 8 which is an example of an embodiment of the present invention. As shown in FIG. 1, the chromatographic separation device 8 includes unit packed columns 11 to 20 packed with an adsorbent connected in series, and a raw material solution and an eluent passed through the unit packed columns 11 to 20 are It has a circulation system 100 that can circulate.

  The unit packed tower 11 is connected to the unit packed tower 12 by a pipe 111, the unit packed tower 12 is connected to the unit packed tower 13 by a pipe 112, and the unit packed tower 13 is connected to the unit packed tower 14 by a pipe 113. The tower 14 is connected to the unit packed tower 15 by a pipe 114. The unit packed column 15 is connected to a unit packed column 16 (hereinafter sometimes referred to as a low pressure unit packed column) by a pipe 115 provided with a shielding valve Z. The unit packed tower 16 is connected to the unit packed tower 17 by a pipe 116, the unit packed tower 17 is connected to the unit packed tower 18 by a pipe 117, and the unit packed tower 18 is connected to the unit packed tower 19 by a pipe 118. The tower 19 is connected to the unit packed tower 20 by a pipe 119. The unit packed tower 20 is connected to the unit packed tower 11 by a pipe 120 provided with a pump 122. Thus, the circulation system 100 is configured by the unit packed towers 11 to 15 and 17 to 20, the unit packed tower 16, the pipes 111 to 120, the pump 122, and the shielding valve Z.

  In the pipe 115, a pipe 42 and a branch pipe 66 are connected between the shielding valve Z and the unit packed tower 16. The pipe 42 is provided with a raw material liquid supply valve f, and the pipe 42 is connected to the raw material liquid supply pump 40.

  The branch pipe 66 is a pipe connected to the pipe 52. The pipe 52 is connected to the eluent supply pump 50. The pipe 52 is connected to branch pipes 61 to 70, and the branch pipes 61 to 70 are respectively provided with eluent supply valves D1 to D10 (hereinafter sometimes collectively referred to as eluent supply valves D). The branch pipe 61 is the pipe 120, the branch pipe 62 is the pipe 111, the branch pipe 63 is the pipe 112, the branch pipe 64 is the pipe 113, the branch pipe 65 is the pipe 114, the branch pipe 66 is the pipe 115, and the branch pipe. 67 is connected to the pipe 116, the branch pipe 68 is connected to the pipe 117, the branch pipe 69 is connected to the pipe 118, and the branch pipe 70 is connected to the pipe 119.

  In the pipe 115, a pipe 170, a branch pipe 135, and a branch pipe 155 are connected between the shielding valve Z and the unit packed tower 15. The piping 170 is provided with an extraction valve B5.

  The branch pipe 135 is a pipe connected to the pipe 130. The pipe 130 is connected to the pipe 120 via the extraction valve C10. Moreover, the piping 130 is connected with branch piping 131-139, and extraction valves C1-C9 are provided in the branch piping 131-139, respectively. The branch pipe 131 is the pipe 111, the branch pipe 132 is the pipe 112, the branch pipe 133 is the pipe 113, the branch pipe 134 is the pipe 114, the branch pipe 135 is the pipe 115, the branch pipe 136 is the pipe 116, and the branch pipe. Reference numeral 137 denotes a pipe 117, branch pipe 138 is connected to a pipe 118, and branch pipe 139 is connected to a pipe 119.

  The branch pipe 155 is a pipe connected to the pipe 150. The pipe 150 is connected to the pipe 120 via the extraction valve A10. The pipe 150 is connected to the branch pipes 151 to 159, and the branch pipes 131 to 139 are provided with extraction valves A1 to A9, respectively. The branch pipe 151 is the pipe 111, the branch pipe 152 is the pipe 112, the branch pipe 153 is the pipe 113, the branch pipe 154 is the pipe 114, the branch pipe 155 is the pipe 115, the branch pipe 156 is the pipe 116, and the branch pipe. Reference numeral 157 is connected to the pipe 117, the branch pipe 158 is connected to the pipe 118, and the branch pipe 159 is connected to the pipe 119.

  The unit packed towers 11 to 15 and 17 to 20 are filled with an adsorbent to form a packed bed 101. The adsorbent of the packed bed 101 is not particularly limited as long as it has a selective adsorption capability with respect to two or more components contained in the raw material liquid. For example, ion-exchange resin, silica gel, ODS (octadecyl group) Bonded silica gel; silica gel having a long-chain aliphatic octadecyl group introduced), synthetic adsorbent, and the like. These may be used alone or in combination of two or more. The type and combination of the adsorbent can be determined according to the component to be separated. Moreover, the average particle diameter and the degree of crosslinking of the adsorbent are not particularly limited, and can be determined according to the component to be separated.

The flow path length of the packed bed 101 is not particularly limited, and can be determined in consideration of the components in the raw material liquid, the purity of the obtained fraction, and the like. Here, the channel length is a distance through which the raw material liquid and the eluent flow through the packed bed 101 or 106.
Further, the area of the cross section perpendicular to the flow direction of the raw material liquid and / or the eluent in the packed bed 101 (hereinafter sometimes simply referred to as a cross-sectional area) is not particularly limited, and the processing amount of the raw material liquid is taken into consideration. Is preferably determined.

  The unit packed tower 16 is a unit packed tower in which a packed bed 106 having a shorter flow path length is formed as compared with the packed bed 101 of the other unit packed towers 11 to 15 and 17 to 20 constituting the circulation system 100. In addition, the unit packed tower 16 is a unit packed tower in which a packed bed 106 having a larger cross-sectional area than the packed bed 101 of the other unit packed towers 11 to 15 and 17 to 20 constituting the circulation system 100 is formed. is there.

The unit packed tower 16 is filled with an adsorbent to form a packed bed 106.
The adsorbent is filled so that the flow path length of the packed bed 106, that is, the height of the packed bed 106 is lower than the height of the packed bed 101 that is the flow path length of the packed bed 101. The ratio of the flow path length of the packed bed 106 to the flow path length of the packed bed 101 is not particularly limited, and can be determined according to the components of the raw material liquid and the separation performance required for the chromatographic separation device 8. For example, it is preferable that the ratio represented by the flow path length of the packed bed 106 / the flow path length of the packed bed 101 is determined in a range of 0.1 or more and less than 1. If it is less than 0.1, the separation performance in the unit packed column 106 is remarkably lowered, and the influence on the separation performance of the entire chromatographic separation apparatus 8 may be increased. This is because if it is 1 or more, the liquid flow differential pressure in the unit packed column 16 cannot be effectively reduced. Moreover, in order to ensure separation performance, the flow path length needs to be a certain length.

  Further, the adsorbent is filled so that the cross-sectional area of the packed bed 106 is larger than the cross-sectional area of the packed bed 101. The ratio of the cross-sectional area of the filling layer 106 to the cross-sectional area of the filling layer 101 is not particularly limited. It can be determined according to the separation accuracy required for the chromatographic separation device 8. For example, it is preferable that the ratio represented by the cross-sectional area of the filling layer 106 / the cross-sectional area of the filling layer 101 is determined in the range of more than 1 and 2 or less. This is because if the ratio is 1 or less, the linear velocity (LV) of the raw material liquid or the eluent in the unit packed column 16 cannot be effectively reduced. If it exceeds 2, the flow path length of the packed bed 106 becomes too short, the separation performance in the unit packed column 106 is significantly lowered, and the influence on the separation performance of the entire chromatographic separation apparatus 8 may be increased. . Moreover, in order to ensure separation performance, the flow path length needs to be a certain length. Note that LV is a flow rate per unit area per unit time and is a linear velocity expressed in m / h.

  The type of adsorbent of the packed bed 106 is the same as the type of adsorbent of the packed bed 101. Further, the adsorbent of the packed bed 106 may be different from the adsorbent of the packed bed 101 in average particle diameter and degree of crosslinking. Note that the adsorbent of the packed bed 106 and the adsorbent of the packed bed 101 are preferably the same. This is because the use of the same adsorbent as the packed bed 101 reduces the complexity of maintenance. In addition, since the adsorbent having different separation performance for reducing the influence of pressure loss is not used for the packed bed 106, the separation performance of the chromatographic separation device 8 can be maintained.

  The ratio of the volume of the filler layer 106 to the volume of the filler layer 101 is not particularly limited, but is preferably substantially the same. If the volumes of the packed beds 101 and 106 are the same, even if the flow path length in the packed bed 106 is shortened, the separation performance equivalent to that of the packed bed 101 is maintained and the separation performance of the chromatographic separation apparatus 8 as a whole is prevented from being lowered. Because it can. In particular, the simulated moving bed type chromatographic separation apparatus performs separation while switching the supply position of the raw material liquid or the eluent and the extraction position of an arbitrary fraction to the downstream side. It is preferable that the volume of the packed bed of the unit packed column is substantially equal. Here, as “substantially equivalent”, it is preferable that the ratio represented by the volume of the packed bed 101 / the volume of the packed bed 106 is 1 / 1.05 to 1.05 / 1. This is because if the volume ratio is within such a range, the packed bed 101 and the packed bed 106 can maintain the separation performance of the entire circulation system 10 without causing a significant difference in separation performance.

  A chromatographic separation method using the chromatographic separation apparatus 8 will be described. The description will be given by taking as an example the case of separating the raw material liquid F containing three components having different adsorptive properties to the adsorbent. The three components are a component having a weak adsorptivity to the adsorbent (A component), a component having a strong adsorbability to the adsorbent (C component), and an adsorbing property to the adsorbent between the A component and the C component. Component (component B).

First, the raw material liquid supply valve f, the eluent supply valve D1, and the extraction valve B5 are opened, and the eluent supply valves D2 to D10, the extraction valves A1 to A10, and the extraction valves C1 to C10 are closed. Next, the pump 40 is activated to supply the raw material liquid F to the unit packed tower 16 via the raw material liquid supply valve f, and the pump 122 is activated to supply the liquid in the circulation system 100 from the unit packed tower 16. The unit packed towers 17, 18, 19, 20, 11, 12, 13, 14, and 15 are passed through the circulation system 100 in this order. Moreover, the pump 50 is started and the eluent D is supplied to the unit packed column 11 through the eluent supply valve D1. Then, the B component fraction (B fraction) enriched in the unit packed column 15 is supplied to the pipe 170 via the extraction valve B5 provided upstream of the shielding valve Z in the circulation direction in the circulation system 100. Extract. During this time, the A fraction and the C fraction are separated in the circulation direction, and an adsorption zone is formed in the circulation system 100.
At the same time, the extraction valve A8 can be opened to extract the A component fraction (A fraction) enriched in the unit packed column 18 from the branch pipe 158 to the pipe 150. Furthermore, the extraction valve C2 is opened, and the C component fraction (C fraction) enriched in the unit packed column 12 can be extracted from the branch pipe 132 to the pipe 130 (first step).

  In the second step following the first step, the supply of the raw material liquid F is stopped, and the supply position of the eluent D, the extraction position of the A fraction, and the extraction position of the C fraction are adjusted to the movement of each enriched fraction. Then, the operation of switching the tower one by one to the downstream side in the circulation direction is performed. Thereby, the A fraction moves in the circulation system 100 to the downstream side in the circulation direction. On the other hand, by moving the supply position of the eluent D downstream in the circulation direction, the circulation system 100 apparently moves upstream in the circulation direction, so that the C fraction apparently moves upstream in the circulation direction. The extraction valve A1 is one of the extraction valves A1 to A10 (hereinafter sometimes collectively referred to as the extraction valve A), and the extraction valve A corresponding to the unit packed column enriched with the A fraction is opened, and the extraction valve C1 is opened. -C10 (hereinafter sometimes collectively referred to as "extraction valve C"), and the separation is continuously performed by opening the extraction valve C corresponding to the unit packed column enriched in the C fraction. The A and C fractions can be collected (second step).

  As the second step, for example, the eluent supply valve D2, the extraction valve A9, the extraction valve C3, and the shielding valve Z are opened, the raw material liquid supply valve f, the eluent supply valves D1, D3-D10, and the extraction valves A1-A8, A10. The extraction valves C1, C2, C4 to 10 and the extraction valve B5 are closed, the pump 40 is stopped, and the supply of the raw material liquid F to the circulation system 100 is stopped. Next, the pump 50 is started, and the eluent D is supplied to the unit packed column 12 via the eluent supply valve D2, and the pump 122 is started to circulate the liquid in the circulation system 100. Then, the A fraction enriched in the unit packed column 19 is extracted from the branch pipe 159 to the pipe 150 via the extraction valve A9. Further, the C fraction enriched in the unit packed column 13 is extracted from the branch pipe 133 to the pipe 130 via the extraction valve C3.

  In the operation of the second step, the eluent supply valve D, the extraction valve A, and the extraction valve C to be opened are switched to the eluent supply valve D, the extraction valve A, and the extraction valve C on the downstream side in the circulation direction. Repeated nine times to complete one cycle of the chromatographic separation operation. After the end of the second step, the process returns to the first step. In the chromatographic separation operation, the A and C fractions are continuously separated and the B fraction is intermittently separated by repeating the cycle.

  The raw material liquid F is not particularly limited as long as it contains two or more components, and examples thereof include a sugar liquid in the middle of sucrose production, a biological extract, and a culture liquid obtained by microbial fermentation.

  The eluent D is not particularly limited as long as each component in the raw material liquid is allowed to flow down into the unit packed tower and the components to be separated can be appropriately separated, and can be determined according to the purpose. it can. For example, water, basic aqueous solution such as sodium hydroxide aqueous solution, acidic aqueous solution such as hydrochloric acid aqueous solution, alcohols such as methanol, ethanol, n-propanol, isopropanol, butanol, isobutanol and the like can be mentioned. As the eluent, one kind of these may be used alone, or a mixed solution obtained by mixing two or more kinds may be used as the eluent. The eluent may contain an acid, a base, a buffer, and a salt.

  The supply amount of the raw material liquid F to the unit packed column in the first step is not particularly limited, and is determined in consideration of the components to be separated, the type of adsorbent packed in the unit packed column, the state of the adsorption zone, and the like. It is preferable to do. The amount of eluent D supplied to the unit packed column in the first step is not particularly limited, and should be determined with respect to the components to be separated, the type of adsorbent packed in the unit packed column, the state of the adsorption zone, and the like. Is preferred.

  The supply amount of the eluent D in the second step is not particularly limited, and is preferably determined in consideration of the component to be separated, the type of adsorbent packed in the unit packed column, the state of the adsorption zone, and the like.

In a chromatographic separation apparatus, it is effective to form a packed bed having a long channel length in order to improve the separation performance. On the other hand, when the liquid is passed through the packed bed having a long flow path length, the differential pressure tends to increase. The flow path length in the packed bed is proportional to the increase in the differential pressure.
Here, for example, if the flow path length of the low-pressure unit packed tower is 1 / 1.5 times, the differential pressure becomes 1 / 1.5 times. Moreover, if the cross-sectional area is 1.5 times, the LV during liquid passing will be 1 / 1.5 times. The differential pressure is considered to be proportional to the LV, and the differential pressure during liquid flow can be reduced to 1 / 1.5 times. Further, when the flow path length of the packed bed is 1 / 1.5 times while maintaining the volume of the packed bed of the low-pressure unit packed tower, the sectional area of the packed bed is 1.5 / 1 times, that is, the LV is 1. /1.5 times. As described above, since the differential pressure during liquid flow is proportional to both the flow path length and the LV, the differential pressure during liquid flow is 1 / 1.5 times the ratio of the flow path length and the LV ratio. It is thought that it can be reduced to 1 / 2.25 times obtained by the product of 1 / 1.5 times.

  According to the present invention, some unit packed towers constituting the circulation system have a low-pressure unit in which a packed bed having a shorter flow path length and / or a packed bed having a larger cross-sectional area than other unit packed towers are formed. By setting it as a packed tower, the differential pressure at the time of liquid flow in this low-pressure unit packed tower can be lowered. For this reason, it can suppress that an excessive pressure loss arises as a whole circulation system, and can operate | move, without reducing a flow velocity. Moreover, the pressure specification of a unit packed tower, piping, etc. can be lowered | hung by preventing the pressure rise in the whole circulation system.

  Therefore, since the same adsorbent as the other unit packed towers constituting the circulation system can be packed in the low pressure unit packed tower, it is possible to suppress excessive pressure loss, so that all the unit packed towers constituting the circulation system One type of adsorbent can be supplied. For this reason, the burden in adsorbent management and maintenance can be reduced.

  According to the present invention, the conventional operation method is changed without reducing the separation performance of the entire chromatographic separation apparatus by substantially equalizing the volume of the packed bed of all unit packed towers constituting the circulation system. Without chromatographic separation.

  The unit packed tower for supplying the raw material liquid is most likely to generate a differential pressure due to the influence of the viscosity of the raw material liquid and the adsorbed component on the adsorbent. According to the present invention, when the unit packed tower for supplying the raw material liquid is fixed, by making the unit packed tower a low-pressure unit packed tower, the increase in the differential pressure due to the viscosity of the raw material liquid and the adsorbing component is reduced, The influence of the pressure loss of the entire circulatory system can be suppressed.

  In the above-described embodiment, the shielding valve is provided only on the upstream side pipe of the unit packed tower to which the raw material liquid is supplied among the pipes connecting adjacent unit packed towers, but the shielding valve is provided at a plurality of locations. It may be done.

  In the above-described embodiment, the pipe for supplying the raw material liquid is connected only to the low-pressure unit packed tower, but a plurality of branch pipes connected to the pipe for supplying the raw material liquid are provided, and the branch pipe is a plurality of units. It may be connected to a packed tower. With this configuration, the unit packed column for supplying the raw material liquid, the unit packed column for supplying the eluent, the unit packed column for extracting the A fraction, and the unit packed column for extracting the C fraction are sequentially maintained while maintaining a certain positional relationship. It is possible to perform chromatographic separation in which the raw material is continuously supplied by moving to the unit packed tower on the downstream side in the circulation direction.

  In the above-described embodiment, the circulation system has a low-pressure unit packed column in which a packed bed having a shorter channel length and a larger cross-sectional area is formed than other unit packed columns. However, the packed bed of the low-pressure unit packed column may only have a shorter channel length or a larger cross-sectional area than the packed bed of other unit packed columns.

  In the above-described embodiment, only the unit packed column to which the raw material liquid is supplied is a low-pressure unit packed column in which a packed bed having a shorter flow path length and a larger cross-sectional area than other unit packed columns is formed. Yes. However, the present invention is not limited to this, and any of the unit packed columns constituting the circulation system may be a low pressure unit packed column, or a plurality of unit packed columns may be low pressure unit packed columns. However, in the chromatographic separation apparatus in which the unit packed tower to which the raw material liquid is supplied is fixed, the unit packed tower to which the raw material liquid is supplied is used as the low pressure unit packed tower in order to suppress the increase in the differential pressure due to the viscosity of the raw material liquid. It is preferable that On the other hand, in the chromatographic separation apparatus in which the unit packed tower to which the raw material liquid is supplied is not fixed, the packed bed of the low-pressure unit packed tower is preferably substantially the same volume as the packed bed of the other unit packed tower. . This is to make the separation performance of each unit packed column substantially equal and stabilize the separation performance of the entire chromatographic separation apparatus.

  In addition, in the above-described embodiment, only one of the unit packed towers constituting the circulation system is formed with a packed bed having a shorter flow path length and a larger cross-sectional area than the other unit packed towers. The combination of unit packed towers forming the circulation system is not limited to this. For example, a packed bed having a short channel length and a large cross-sectional area may be formed in a plurality of unit packed towers among the unit packed towers constituting the circulation system. Further, for example, a low-pressure unit packed column and a unit packed column in which a packed bed having a long channel length is formed may be alternately arranged. Further, for example, packed packing layers having different flow path lengths and / or cross-sectional areas may be formed in all unit packed towers constituting the circulation system.

  The combination of the length of the flow path in the packed bed and the size of the cross-sectional area is preferably selected in consideration of the properties of the raw material liquid, the purity of the obtained fraction, and the like. According to such an embodiment, even in the pseudo moving bed type chromatographic separation apparatus in which the unit packed tower for supplying the raw material liquid is moved to perform chromatographic separation, the increase in the differential pressure can be effectively controlled.

  In the above-described embodiment, chromatographic separation is performed using a raw material liquid containing three components, but the target to be separated may be two components or four or more components.

It is a schematic diagram which shows an example of the chromatographic separation apparatus of this invention.

Explanation of symbols

8 Chromatographic Separator 100 Circulation System 11-20 Unit Packing Tower 101, 106 Packed Bed 111-120 Piping 122 Pump Z Shielding Valve

Claims (2)

A plurality of unit packed towers filled with an adsorbent and formed with packed layers having different channel lengths of the raw material liquid and the eluent and / or cross-sectional areas orthogonal to the flow direction of the raw material liquid and the eluent. The unit system is connected in series and has a circulation system configured to circulate the raw material liquid and the eluent passed through the unit packed column, and the circulation system is a unit packing in which a packed bed having a substantially equal volume is formed. A chromatographic separation device comprising a tower . The unit packed column to which the raw material liquid is supplied has a packed bed in which the flow path length of the raw material liquid and the eluent is shorter than that of the other unit packed towers constituting the circulation system, and / or the flow of the raw material liquid and the eluent. 2. The chromatographic separation apparatus according to claim 1 , wherein the chromatographic separation apparatus is a unit packed column in which a packed bed having a large cross-sectional area perpendicular to the liquid direction is formed.

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