JPS6312490B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to bead-shaped cyclodextrin polymers, and more particularly to a method for producing bead-shaped insoluble resins by reacting cyclodextrin with a crosslinking agent.

Cyclodextrin is a cyclic oligosaccharide in which six or more glucose units are α-1,4-linked,
It has a cylindrical cavity within its molecule, and forms clathrate compounds by incorporating various substances into it. To form this clathrate,
The shape and size of the molecule of the clathrate must fit into the cavity of the cyclodextrin, and the degree of compatibility causes a difference in the affinity between the clathrate and the cyclodextrin. By using this, it is possible to separate and divide various substances.

There are several methods for this separation and division, but
In particular, a method of polymerizing cyclodextrin to form an insoluble resin and using it as a packing material for column chromatography is viewed as promising.

Now, as a method for producing an insoluble cyclodextrin resin, for example, a method is known in which cyclodextrin is made to react with epichlorohydrin, a diepoxy compound, a diisocyanate, an acrylamide derivative, etc. to form a crosslinked polymer. However, the resins obtained by these methods are gel-like and have the disadvantage of swelling when absorbing water, etc. Therefore, in order to use them in columns, etc., it is necessary to increase the mechanical strength and the circulation of the solvent. It is necessary to improve the properties, and for this purpose it is desirable that the beads be shaped like beads.

In order to make bead-shaped cyclodextrin polymers, cyclodextrin dissolved in a high concentration in an alkaline aqueous solution is dispersed in a solvent such as toluene, xylene, or methyl isobutyl ketone, and then reacted with epichlorohydrin, ethylene glycol diglycidyl ether, etc. There are known ways to do this. However, in these methods, the solvent in the organic phase or the surfactant used to stabilize the emulsion is incorporated into the generated beads and is difficult to completely remove by washing, resulting in elution during use. It has drawbacks.

In view of these circumstances, the present inventors have conducted intensive research to improve the manufacturing method of bead-shaped cyclodextrin polymers. As a result, the above-mentioned drawbacks have been overcome by using the crosslinking agent itself as the organic phase, which is the dispersion medium. We have found that improvements can be made, and based on this we have accomplished the present invention.

That is, in the present invention, cyclodextrin, which has been polymerized by a crosslinking agent to the extent that it does not become insolubilized, is dispersed in a crosslinking agent as an organic phase, and the cyclodextrin is heated at 30°C to
The present invention provides a method for producing bead-like cyclodextrin polymers by reacting at 80°C.

In the method of the present invention, the cyclodextrins used are α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, and mixtures thereof, and these cyclodextrins must be polymerized in advance to the extent that they do not become insolubilized. . Examples of crosslinking agents used for polymerization include epichlorohydrin, ethylene glycol diglycidyl ether, 1,4-butanediol diglycidyl ether, 1,2,7,8-diepoxyoctane, and ethylene glycol bis(2-chloroethyl) ale. etc. are preferably used. The molecular weight of this polymerized cyclodextrin is preferably as large as possible within a range that does not cause insolubilization, and when epichlorohydrin is used, the average molecular weight is about 5,000 to 8,000. Usually, in this polymerization, 0.3 to 1.0 parts by weight of sodium hydroxide and 1 part by weight of water are added to 1 part by weight of cyclodextrin.
It is desirable to use a range of 0.1 to 1.0 parts by weight of sodium borohydride and 0.1 to 1.0 parts by weight of the crosslinking agent, and it is particularly necessary to set the amount of the crosslinking agent within a range that does not cause insolubilization. The temperature in this polymerization reaction is preferably 30°C to 80°C, particularly preferably around 50°C. Usually 100~
By slowly dropping the crosslinking agent while stirring at a rotational speed of about 500 rpm, the process is completed in 30 minutes to 2 hours, and a syrupy, highly viscous liquid is obtained.

Next, remove bubbles from this syrup-like liquid, and if the viscosity is too high, add an appropriate amount (0.1 to 0.5 parts by weight) of water to adjust the viscosity to easily disperse in the organic phase, and then add 1 part by weight of cyclodextrin. 5~
Add 100 parts by weight of crosslinking agent and maintain at the above temperature.
Stir and react at a rotation speed of 500 to 3000 rpm. Although the amount of crosslinking agent and the stirring speed may be outside the above range, generally the larger the amount of crosslinking agent and the faster the stirring speed, the smaller the particle size of the beads produced. Further, the crosslinking agent used in this step may be different from that used in the step of producing the water-soluble polymer. Bead production usually begins in 30 minutes to 2 hours and is completed in 2 to 10 hours.

The product thus obtained is washed several times with acetone or lower alcohol, then washed with distilled water until the pH of the washing water becomes neutral, and then dehydrated with acetone or lower alcohol and dried. A bead-shaped cyclodextrin polymer is obtained. In order to remove the unreacted crosslinking agent remaining in the beads, the beads are immersed in a 10-30% aqueous sodium hydroxide solution at 40°C to 60°C for 2 to 5 hours, and then washed, dehydrated, and washed in the same manner as above. Perform drying.

A feature of the method of the present invention is that a bead-shaped cyclodextrin polymer is produced by preparing a polymer that has been polymerized in advance to the extent that it does not become insolubilized and dispersing it in a large amount of crosslinking agent. In comparison, since no dispersion medium other than a crosslinking agent is used, the produced beads can be easily purified and beads containing no impurities can be obtained.

Next, the present invention will be explained in more detail with reference to Examples.

Example 1 2g of powdered β-cyclodextrin and 1.5ml of water
Add 2.5 ml of 40% aqueous sodium hydroxide solution and 20 mg of sodium borohydride to make a homogeneous solution, and keep this at 50℃.
Add 1 ml of epichlorohydrin dropwise over about 10 minutes while stirring at a speed of 200 rpm. After stirring for another 2 hours, add 2 ml of water to remove bubbles. Add 50 ml of epichlorohydrin to the resulting syrupy liquid and keep at 50°C. The mixture was stirred for 4 hours at a rotation speed of 2000 rpm. The obtained beads were separated by filtration, washed three times with 50 ml of acetone each time, washed with distilled water until the pH of the washing solution became neutral, and then immersed in distilled water for one day. It was dehydrated by soaking for an hour and dried with phosphorus pentoxide in a vacuum desiccator for 1 day. In this way, 2.9 g of bead-shaped β-cyclodextrin polymer having a particle size of 20 to 200 mesh was obtained.

Example 2 2g of powdered β-cyclodextrin and 1.5ml of water
Add 2.5 ml of 40% aqueous sodium hydroxide solution and 20 mg of sodium borohydride to make a homogeneous solution, and keep this at 50℃.
While stirring at a speed of 200 rpm, add 1.5 ml of 1,4-
Butanediol diglycidyl ether was added dropwise over about 10 minutes, and after further stirring for 2 hours, 2 ml of water was added to form a syrupy solution. Add 50ml of 1,4-butanediol diglylyle ether to this.
The mixture was stirred at a rotation speed of 2000 rpm for 4 hours while maintaining the temperature at 50°C. The obtained beads were separated by filtration, washed three times with 50 ml of acetone each time, washed with distilled water until the pH of the washing solution became neutral, and then immersed in distilled water for one day. Soak for an hour and dehydrate.
It was dried with phosphorus pentoxide in a vacuum desiccator for 1 day. In this way, 1.9 g of bead-like β-cyclodextrin polymer having 20 to 200 meshes was obtained.

Claims (1)

[Claims] 1. In the absence of an organic solvent, cyclodextrin is first crosslinked with epichlorohydrin or a diepoxy compound to an average molecular weight of about 5000 to 8000,
A method for producing a bead-shaped cyclodextrin polymer, which comprises dispersing this reaction product in epichlorohydrin or a diepoxy compound, and granulating it while crosslinking it until it becomes insolubilized.