WO2004082828A1

WO2004082828A1 - Tubular column structure

Info

Publication number: WO2004082828A1
Application number: PCT/JP2004/003674
Authority: WO
Inventors: Keiichi Hirano
Original assignee: Nihon Medi-Physics Co., Ltd.
Priority date: 2003-03-19
Filing date: 2004-03-18
Publication date: 2004-09-30
Also published as: JP2004283647A; TW200505539A

Abstract

A tubular column structure formed by sealing an ion exchange resin in a tubular column capable of preventing problems with a conventional structure wherein solvent is hard to pass the resin due to an increase in flow resistance of solvent by the expansion of the resin and a column efficiency is lowered by clearances in the resin due to the shrinkage of the resin. A pair of filters (10) and (12) are disposed in the tubular column (2) so as to hold the ion exchange resin (8), and at least one of the filters is slidably installed along the inner peripheral surface of the tubular column. Thus, the volume of a space filled with the ion exchange resin can be increased according to the expansion of the ion exchange resin and decreased according to the shrinkage thereof.

Description

Mechanized cylindrical column structure

The present invention relates to a cylindrical column structure in which an ion exchange resin is sealed in a cylindrical column. The cylindrical column structure according to the present invention can be applied to, for example, an ion exchange column or a column used for an organic compound labeling reaction. Background technology

Conventionally, ion-exchange column uniformly packed with 100% of the capacity of the ion exchange resin to the column tube volume, although the flow resistance of even the solvent polarity by injecting the same solvent is about 1 Kg f Zcm ² Thereafter, when a solvent having a different polarity is injected into the ion exchange column, the ion exchange resin expands, causing a problem that the solvent cannot pass even when a pressure of 15 OKg f / cm ² is applied.

In addition, when the column is filled with the ion exchange resin taking into account the expansion rate of the ion exchange resin, and when a solvent with a different polarity is injected into the ion exchange column, the expansion of the ion exchange resin starts immediately after that. However, in this case, even if the ion exchange resin expands completely, the density of the resin does not increase and the fluidity of the solvent does not decrease. However, the ion-exchange resin that has been swollen by solvents of different polarities contracts when the solvents of different polarities finish flowing. A problem occurs in that the contact efficiency and reaction efficiency decrease.

Incidentally, the fluorine has been made to use ion exchange resins in the production of radioisotope-labeled organic compound ⁸ F-labeled organic compound), as such I-exchange resins, Nu cl. Me d. B iol. Vol. 17, No. 3, p. 273-279 (1990) There is a 4-aminopyridinium resin prepared using the Merrifield resin described in Non-Patent Document 1. . Since the pyridinium salt of the above 4-aminopyridinium resin is a hydrophilic group, this 4-aminopyridinium resin is highly hydrophilic and swells in a highly polar solvent. On the other hand, when a solvent having low polarity is passed, the resin shrinks.

As described above, the swelling state of the 4-aminopyridinium resin changes according to the polarity of the solvent. When the resin packed in the column swells, the back pressure increases when passing the solution through this column, and the fluidity deteriorates. On the other hand, when the resin shrinks, the column efficiency decreases.

On the other hand, in the aforementioned literature Nuc 1. Med. Biol. Vol. 17, No. 3, pp. 273-279 (1990), the flow characteristics of 4_aminopyridinium resin were To improve, a fibrous cation exchange resin is added to the column. However, the addition of fibrous cation exchange resin increases the production cost of the column. Also, when the compounding ratio of the fibrous cation exchange resin is low, that is, the compounding ratio of 4-aminopyridinium resin is high, and the collection rate of [ ¹⁸ F] fluoride ion is high, the substrate The ratio of the resin to which [ ¹⁸ F] fluoride ion which does not contribute to the reaction with the resin is increased, and the reaction yield is disadvantageously reduced. Also, Japanese Patent Application Laid-Open No. 8-325169 [Patent Document 1] discloses that a phosphonium resin is used as an ion exchange resin used for producing an ¹⁸ F-labeled organic compound. Since the phosphonium resin has low hydrophilicity, it has a low degree of swelling in polar solvents such as water, acetonitrile, and dimethyl sulfoxide. For example, the solvent uptake of a 4-aminopyridinium resin (active group; pyridinium salt content: 1.2 mmol Zg) synthesized from a conventional commercially available Merrifield resin is 0.6 gZg for acetonitrile, In the case of 1. It is 1.1 g / g. On the other hand, the solvent uptake amount of a phosphonium resin containing a phosphonium salt as an active group in a range of 0.5 to 1.6 mmo1 / g is 0.3 g / g or less for acetonitrile, 0.5 gZg or less for water.

Further, since the phosphonium resin has a low density of the phosphonium salt on the resin, the steric hindrance that hinders the flow of the polar solvent is small. For this reason, the back pressure of the column is prevented from rising, and the flowability of the polar solvent is good. Also, phosphonium tree Since the fat does not easily shrink, the column efficiency does not easily decrease. Thus the content of phosphate Honiumu salt 0. 5~1. 6mmo 1 Zg phosphonium © resinless is in the range of, easy to handle, and _c are suitable for use in packed in a column container, fiber Since there is no need to use a state cation exchange resin, the production cost can be reduced. It is also stated that there is no risk of yield reduction due to mixing of fibrous cation exchange resin.

However, the inventor obtained a phosphonium resin of the same kind as described in Patent Document 1 and conducted an experiment.When flowing a solvent having a different polarity, the resin swelled about twice, so that 150 kg / cm It was confirmed that the solvent did not flow even when the pressure of ² was applied.

JP-A-8-155207 (Patent Literature 2) discloses a method of using a movable stopper to expand and contract a resin in order to prevent the solvent from flowing due to the expansion of the ion exchange resin in the ion exchange resin sealed input ram. Have been proposed. However, in this column, since the ion exchange resin is almost completely filled between the front and rear stoppers, it may not be able to follow the expansion twice as much as the resin. In addition, since the movable tap moves by the force of the spring, frequent or large movement may cause a failure. In particular, in a column system where gas flows, the sealing performance is reduced and leakage may occur.

Nu c 1. Med. B i o l. Vo l. 17, No. 3, p p. 27 3-27 9 (1 90 90)

Japanese Patent Application Laid-Open No. H8-32 25 16 9

Japanese Patent Application Laid-Open No. 8-1555007

As described above, the ion-exchange resin pushed into the limited rigid space expands due to solvents having different polarities. As a result, the flow resistance of the solvent increases, and it becomes difficult to pass the solvent.

In addition, in the case of a column prepared taking into account the expansion coefficient of the ion exchange resin, after the ion exchange resin expands, a gap between the contracted ion exchange resins occurs at that location, resulting in extremely low power ram efficiency. The problem that it falls is produced. Disclosure of the invention

The present invention has been made in view of the above circumstances, and the volume of a space filled with an ion exchange resin increases as the ion exchange resin expands and decreases as the ion exchange resin contracts, thereby reducing the resin content. A tube that can prevent the flow resistance of the solvent from increasing due to expansion, making it difficult to pass the solvent through the resin, and preventing the column efficiency from decreasing due to gaps between the resins due to resin contraction. It is intended to provide a columnar structure.

The present inventors have conducted intensive studies to achieve the above object, and as a result, in a cylindrical column in which an ion exchange resin is sealed, a pair of filters are arranged in a cylindrical force ram so as to sandwich the ion exchange resin. In addition, at least one of the filters described above has a function that can be moved by the expansion force of the ion-exchange resin and a function that can be moved by the force of the solvent or gas in accordance with the contraction of the ion-exchange resin. It has been found that the above-mentioned object can be achieved by providing.

The present invention has been made based on the above findings, and has a cylindrical column structure in which an ion exchange resin is sealed in a cylindrical column, wherein a pair of filters are cylindrical so as to sandwich the ion exchange resin. A cylindrical column structure, wherein the cylindrical column structure is arranged in a column, and at least one of the pair of filters is slidably provided along an inner peripheral surface of the cylindrical column. I will provide a. The cylindrical column structure of the present invention fills the cylindrical column with an amount of ion exchange resin that does not exceed the column capacity even if it expands to the maximum, and the slidable filters provided on both sides of the ion exchange resin move. By doing so, even when the ion exchange resin expands, the density of the ion exchange resin is maintained, and the flow resistance of the solvent can be kept low. If the ion-exchange resin shrinks after expanding, the filler moves by the force of the solvent or gas and returns to the best column state while collecting the shrinked resin with gaps.

As described above, in the tubular column structure of the present invention, the volume of the space filled with the ion exchange resin increases following the expansion of the ion exchange resin due to the sliding of the filter. As the resin shrinks, the flow resistance of the solvent increases due to the expansion of the resin, making it difficult to pass the solvent through the resin, and the shrinkage of the resin creates a gap between the resins. Column efficiency can be prevented from lowering. The cylindrical column structure of the present invention can flexibly cope with expansion and contraction of the ion exchange resin, does not require special mechanical functions to move the filter, does not cause clogging, and has a high column efficiency. This is an extremely simple and advanced invention that can obtain a column that does not impair the performance. Brief explanation of drawings

FIG. 1 is a longitudinal sectional view schematically showing one example of a cylindrical column structure according to the present invention.

FIG. 2 is a longitudinal sectional view showing an example of use of the cylindrical column structure according to the present invention. FIG. 3 is an explanatory diagram showing a state where the column having the structure of FIG. 1 is incorporated in a line.

FIG. 4 is a longitudinal sectional view schematically showing another example of the cylindrical column structure according to the present invention.

(A) to (e) of FIG. 5 are each a longitudinal sectional view schematically showing still another example of the cylindrical column structure according to the present invention.

FIG. 6 is a vertical sectional view schematically showing still another example of the cylindrical column structure according to the present invention.

FIG. 7 is a longitudinal sectional view schematically showing still another example of the cylindrical column structure according to the present invention.

FIG. 8 is a longitudinal sectional view schematically showing still another example of the cylindrical column structure according to the present invention.

Next, embodiments of the present invention will be described with reference to the drawings, but the present invention is not limited to the following examples. FIG. 1 shows an example of a cylindrical column structure according to the present invention. FIG.

In FIG. 1, fixed plugs 6 having communication holes 4 are provided at both ends of the cylindrical column 2, and a granular ion exchange resin 8 is sealed inside the cylindrical column 2. Filters 10 and 12 are arranged before and after the ion exchange resin 8 so as to be in contact with the inner peripheral surface of the column 2. One filter 10 is arranged so as to be freely slidable along the inner peripheral surface of the mirror-finished column 2. The other filter 12 may be freely movable like the one filter 10, may be substantially fixed to the inner peripheral surface of the force ram 2, and is mounted so as to have a certain sliding resistance. May be.

Fig. 1 shows the ion-exchange resin 8 in a contracted state, and a gap between one filter 10 and the fixing plug 6 is equal to or 2-3 times the volume of the contracted ion-exchange resin 8. Is formed.

Fig. 2 partially shows how the resin column of Fig. 1 is incorporated into a line. The resin column is installed in the vertical direction, and connecting pipes 16 and 18 are connected to fixing plugs 6 and 6, respectively. Then, for example, an aqueous solution containing [ ¹⁸ F] fluoride ion is injected into the ion exchange column from the A direction, and the solvent is discharged from the C direction. Subsequently, a solvent having a different polarity from the B direction, for example, acetonitrile is injected here, and the ion exchange column is dehydrated, and the solvent is similarly discharged from the C direction.

In the present invention, the term ion exchange resin is used in the broadest sense. That is, the ion exchange resin in the present invention includes a cation exchange resin (CER), an anion exchange resin (AER), an ion retardation resin (IRR), a phase transfer catalyst resin (PTC), and the like.

Specific examples of PTC include a phosphonium resin having an active group of tributylphosphonium (the carrier is a crosslinked chloromethylstyrene-styrene copolymer; JP-A-8-325169). Ammonium resin with triptylmethylammonium (carrier is a crosslinked chloromethylstyrene-styrene copolymer), pyridinum resin with active groups of 4-dimethylaminopyridinium (carrier is crosslinked) Chloromethylstyrene-styrene copolymer, Merrifield resin (Non-patent document 1), and the like. As the form of the ion exchange resin, granules having a particle size of 50 to 400 mesh are preferably used, but fibrous materials having other particle sizes and other sizes can also be used.

As the filter in the present invention, for example, a polytetrafluoroethylene filter, a polyethylene filter, a polypropylene filter, a sintered filter, a glass filter, and the like can be used. It needs to be changed depending on the mesh size. For example, since the diameter of a resin of 400 mesh is 63.5 m, a filter having a pore diameter of 50 m or less is selected. Since the diameter of the 50-mesh resin is 508 m, a filter having a pore diameter of 500 m or less is selected. Therefore, the applicable filter pore size differs depending on the size of the resin, but usually a filter having a pore size of about 10 to 500 is used.

It is appropriate that the thickness of the filter is in the range of 1 Z 15 to 1 Z 1 of the column diameter, or 1.5 mm or more. Further, it is appropriate that the diameter of the filter is 2 mm or more. The most preferable example of the filter is a polytetrafluoroethylene filter having a diameter of 6 mm, a thickness of 2 mm, and a pore diameter of 10 m. Filters can be of any shape, such as triangular, square, polygonal, circular, etc., if manufacturable.

The material of the cylindrical column is metal, plastic, glass, etc. that does not change shape significantly at around 100 ° C and has the property of conducting heat, such as iron, copper, stainless steel, glassy carbon, carbon, Examples include silicon, titanium, silver, polyethylene, polypropylene, polyetheretherketone, and the like. In addition, materials other than the above may be selected in consideration of solvent invasion and the like. It is desirable that the inner surface of the cylindrical column be mirror-finished in order to reduce the sliding resistance in the filter. As a method of manufacturing a cylindrical column, a method of making a hole, shaving, or processing a thread using a machine such as a lathe can be adopted. Also, if a cylindrical column tube can be manufactured, For example, an arbitrary shape such as a rectangle, a rectangle, a polygon, and a circle can be used. Figure 3 is an example that incorporates a production line of ¹⁸ F-labeled organic compound cylindrical column of FIG. In FIG. 3, reference numeral 51 denotes a target box, 52 denotes an evening water container, 53 denotes a syringe pump, 54 denotes a three-way valve, 55 denotes a resin column for labeling reaction, 56 denotes a collection container, 57 denotes a syringe pump, and 58 denotes a syringe pump. Acetonitrile container, 59 is a three-way valve, 60 is a three-way valve, 61 is a waste liquid container, 62 is a triflate container, 63 is a three-way valve, 64 is a three-way valve, 65 is a cation exchange resin column, and 66 is sterile water. A container, 17 is a syringe pump, 68 is a 3-way valve, 69 is a 3-way valve, and 20 is a purification column.

Detailed avoid, but labeling reaction resin column 55 is Do to the present invention tubular column structure, ¹⁸ 0 water containing ^[18 F] water of the raw material rarely charged in the target box 51, the cation exchange resin column 65 The hydrolysis takes place in the desired [ ¹⁸

F] - 2-Dokishi] 3- D-glucose ⁽¹⁸ F- FDG) is purified. Regarding the usage of the cylindrical columns in Figs. 1-3, [ ¹⁸ F] ion collection and ¹⁸ F labeling of glucose ([ ¹ SF] —2-dexoxy; 3-D—glucose) explain.

1. In the column 55, 0.2 mL of the above-mentioned phosphonium resin is sealed.

^2.18 0 water of 1 OML produced is proton irradiation ^[18 F] H ₂ 〇 is passed through the column 55, ¹⁸ F ions are trapped in the resin.

3. When the collection of fluorine into the resin is completed, the resin remains in the same state as when it was filled, and the volume of the resin does not change.

4. Introduce helium gas, nitrogen gas, etc. into the column to discharge ^180- water from the resin. This water is recovered for subsequent reuse.

5. Next, the dehydrated acetonitrile is injected into column 55.

6. Then, the acetonitrile penetrates into the gaps between the resins that cannot contact with water, and the resin starts to expand.

7. Further, as the acetonitrile proceeds downstream in the column, The resin and resin expand contact one after another, the resin expands about twice, and the resin spreads to the full column. The filter is pushed by the expansion of the resin, slides inside the column, and approaches the stopper. This avoids consolidation of the resin layer, and the reaction is continued with almost no increase in the flow resistance of acetonitrile.

8. Since water is infinitely soluble in acetonitrile, contacting an appropriate amount of anhydrous acetonitrile with the resin dehydrates the water contained in the resin.

When about 5 times the amount of acetonitrile is brought into contact with 90.2 cc of ion exchange resin, the water in the resin decreases and the resin starts to shrink, and further, about 5 times the amount of acetonitrile is brought into contact with the resin. Then, the shrinkage of the resin ends. At this time, the resin layer acts to create a gap, but is pushed by acetonitrile, and the filter slides in the force ram and attempts to return to the original position. Therefore, no gap is formed in the resin layer and the reaction efficiency of ion exchange does not decrease.

10. Lastly, by passing through TATM (1,3,4,6-tetra-O-acetyl-2 -〇-trifluoromethanesulfonyl 3-D-mannopyranose) together with acetonitrile, a nucleophilic substitution reaction is performed. TATM is ^{1 8} F-labeled, finally hydrolyzed to the ^{^{1 8 F- FDG ([1 8}} F] one 2- Dokishi) 3- D-glucose) is purified.

Here, the movable filter having the cylindrical column structure according to the present invention effectively works, and moves upward in the space of the cylindrical column in accordance with the expansion of the ion exchange resin, but the density of the resin is maintained. The flow resistance of the solvent does not increase. That is, no clogging occurs.

After the solvent is injected to some extent and the expansion of the ion exchange resin reaches the limit, contraction of the ion exchange resin starts. This is due to the dehydration of the water in the ion-exchange resin. The timing is the same. As a result, the filter responds flexibly to the ion-exchange resin, which expands and increases its volume, and then contracts with dehydration, returning it to its original, uniformly filled state. Power ram efficiency can be ensured.

FIG. 4 shows another example of the tubular column structure of the present invention. Inside the column 2, a granular ion exchange resin 8 is sealed. Filters 10 and 12 are arranged before and after the ion exchange resin 8 in the same state as in the example of FIG. A male screw 20 is attached to the outer peripheral surface of the cylindrical force ram 2, and a female screw 24 is provided at an end of the connect pipe 22 connected to the line. The fixing plug 6 is sandwiched between the cylindrical column 2 and the connecting pipe 22 and is not directly fixed to the cylindrical column 2.

FIGS. 5A to 5E show still another example of the tubular column structure of the present invention. A granular ion exchange resin 8 is sealed inside the cylindrical force ram 2. Filters 10 and 12 are arranged before and after the ion exchange resin 8 in the same state as in the example of FIG. These tubular column structures are made in consideration of the resin and filter stability, connection to the line, and reaction efficiency.

FIG. 6 shows still another example of the cylindrical column structure of the present invention. A granular ion exchange resin 8 is sealed inside the cylindrical column 2. Before and after the ion exchange resin 8, filters 10 and 12 are arranged in the same state as in the example of FIG. This example has a structure without a fixed stopper. In the figure, reference numeral 26 denotes packing between the connect tube 28 and the cylindrical column 2.

FIG. 7 shows still another example of the cylindrical column structure of the present invention. A granular ion exchange resin 8 is sealed inside the cylindrical column 2. Before and after the ion exchange resin 8, filters 10 and 12 are arranged in the same state as in the example of FIG. In this example, one of the filters 12 has a flange portion 13 formed on the outer edge thereof, is sandwiched between the cylindrical column 2 and the connect pipe 30 and does not slide, and also has a function of a fixing plug. I have.

FIG. 8 shows still another example of the cylindrical column structure of the present invention. A granular ion exchange resin 8 is sealed inside the cylindrical column 2. Filters 10 and 12 are arranged before and after the ion exchange resin 8 in the same state as in the example of FIG. In this example, the cylindrical column 2 has a packing function. In the figure, reference numeral 32 also serves as a fixing stopper. It is a connecting pipe that is connected to the connection pipe. Since the cylindrical column 2 in this example is to be held in the connect tube 32, there is no disadvantage in strength even if it is made of a plastic such as polyetheretherketone resin.

Claims

Scope of Claim A cylindrical column structure in which an ion exchange resin is sealed in a cylindrical column, and a pair of filters are arranged in the cylindrical force column so as to sandwich the ion exchange resin. A cylindrical force ram structure, wherein at least one of the pair of filters is slidably provided along the inner peripheral surface of the cylindrical column. The tube according to claim 1, wherein the filter slidably mounted along the inner peripheral surface of the cylindrical column slides following expansion and contraction of the ion exchange resin. Column structure. 3. The cylindrical column structure according to claim 1, wherein the ion exchange resin is a granular ion exchange resin and / or a fibrous ion exchange resin. 4. The method according to claim 1, wherein when the ion exchange resin shrinks, a void having a volume equal to or greater than the volume of the ion exchange resin shrinkage is formed in the cylindrical column. 2. The cylindrical column structure according to 1.

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