JPS6020924A - Production of bead-foam insoluble cyclodextrin polymer - Google Patents

Abstract

PURPOSE:To produce the titled polymer which can be readily purified and contains no impurity, by reacting a cyclodextrin having a MW increased to such an extent that it does not become insoluble with a crosslinking agent to form an insoluble polymer. CONSTITUTION:A cyclodextrin having a MW increased to such an extent that it does not become insoluble and an average MW of 5,000-8,000 is obtained by adding 0.3-1.0pt.wt. NaOH, 1-2pts.wt. water, 0.1-1.0wt% sodium borohydride and 0.1-1.0pt.wt. crosslinking agent (e.g., epichlorohydrin) to 1pt.wt. cyclodextrin, reacting the mixture at 30-80 deg.C for 0.5-2hr under agitation at 100-500rpm. 5-100pts.wt. crosslinking agent is added to 1pt.wt. cyclodextrin and the mixture is reacted at 30-80 deg.C for 0.5-2hr under agitation at 500-3,000rpm to obtain an insoluble polymer.

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 has six or more glucose α-1
, 4-linked cyclic oligosaccharide, which has a cylindrical cavity within its molecule, and forms clathrate compounds by incorporating various molecules into it. In order to form this clathrate, the shape and size of the molecule of the encapsulated proboscis must fit into the cavity of the cyclodextrin, and the degree of fit determines the relationship between the encapsulated proboscis and the cyclodextrin. Since there is a difference in the working affinity, it is possible to separate and divide various substances by utilizing this difference.

There are several methods for this separation and division, but one method that is particularly promising is to polymerize cyclodextrin to make it an insoluble resin and use it as a packing material for column chromatography.

Now, as for the manufacturing method of insoluble cyclodextrin resin,
For example, a method is known in which cyclodextrin is made to react with epichlorohydrin, a jepoxy 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 C1 water, etc., and in order to be used in columns, etc., it is necessary to increase mechanical strength and solvent flowability. It is necessary to improve the quality of the particles, and for this purpose it is desirable that they be bead-shaped.

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 produced beads;
Since it is difficult to completely remove by washing, it has the disadvantage that it elutes during use.

In view of these circumstances, the present inventors have conducted extensive research to improve the method for producing bead-shaped cyclodextrin polymers, and have found that the above drawbacks can be overcome by using the crosslinking agent itself as the organic phase, which is the dispersion medium. The present invention has been accomplished based on this discovery.

That is, the present invention produces bead-shaped cyclodextrin polymers by dispersing cyclodextrin, which has been polymerized to such an extent that it does not become insolubilized by a crosslinking agent, in a crosslinking agent as an organic phase and reacting it at 30°C to 80°C. This provides a method to do so.

In the method of the present invention, the cyclodextrin used is α
-Cyclodextrin, β~Cyclodextrin, γ-
Cyclodextrins and mixtures thereof, such as cyclodextrins, must be polymerized in advance to such an 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-jepoxyoctane, 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 dispersion is about 5,000 to 8,000. Usually, in this polymerization, l. and crosslinking agent 0,
It is desirable to use the crosslinking agent in an amount of 1 to 10 parts by weight, and in particular, it is necessary to set the amount of the crosslinking agent within a range that does not cause insolubilization. The temperature in this polymerization reaction is 30'C to 80°C.
is preferable, particularly around 50°C. Usually 1
00 to 500 rl) While stirring at a rotational speed of approximately Tll, slowly drop the crosslinking agent for 30 minutes to
The process is completed in 2 hours and a syrupy, highly viscous liquid is obtained.

Next, remove bubbles from this syrupy liquid, and if the viscosity is too high, add 1 lfi fjt (0.1 to 0.45 parts) of water to adjust the viscosity to easily disperse in the organic phase. , 5 to 10 per part by weight of cyclodextrin
500~ while adding 0 parts by weight of crosslinking agent and keeping at the above temperature.
Stir and react at a rotation speed of 3000 rpm.

The amount of crosslinking agent and stirring speed may be outside the above ranges, but generally the amount of crosslinking agent is large, and The crosslinking agent used may be different from that used in the step of producing the water-soluble polymer.Usually 30 minutes to
Bead formation begins in 2 hours and completes in 2-10 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 unreacted crosslinking agent remaining in the beads,
40°C to 60'G in 30% aqueous sodium hydroxide solution
After soaking for 2 to 5 hours, washing, dehydration, and drying are performed in the same manner as above.

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 2 g of powdered β-cyclodextrin and 1 part of water, '5
2.5 ml of 4096 sodium hydroxide aqueous solution; and 20 ml of sodium borohydride
1 ml of epichlorohydrin was added dropwise over about 10 minutes while stirring at 50°C, and 2 d of condensate stirred for 2 hours was added to form a homogeneous solution. Add 50 d of epichlorohydrin to the resulting syrupy liquid and heat at 50°C.
The mixture was stirred for 4 hours at a rotational speed of 2000 rl) m while maintaining the temperature.

The obtained beads were separated by filtration, and 59 ml of acetone was added.
Wash with distilled water until the pH of the washing solution becomes neutral, and after soaking in distilled water for one day, wash with acetone 1
00ml for 5 hours to dehydrate, and dried in a vacuum desiccator with phosphorus pentoxide 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 1.5 ml of water was added to powdered β-cyclodextrin and kneaded, and 40% aqueous sodium hydroxide solution was added to this mixture.
．． 5 ml and boron hydride) IJium2oIn
9 to make a homogeneous solution, keep this at 50℃ and incubate for 20
While stirring at the speed of orpm, 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 syrup-like solution. To this was added 501 nl of 1,4-butanediol diglycidyl ether, and the mixture was stirred at a rotational speed of 200 rpm for 4 hours while maintaining the temperature at 50'C.

The obtained beads were separated by filtration, washed three times with 5 Qml of acetone each time, washed with distilled water until the pH of the washing solution became neutral, and then submerged in distilled water for one day.
The sample was immersed in 0ml water for 5 hours to dehydrate, and dried in a vacuum desiccator with phosphorus pentoxide for 1 day. In this way 20-2
A beaded β-cyclodextrin polymer of 0.00 mesh was obtained.

Patent applicant: Director of the Agency of Industrial Science and Technology Kawaguchi 1 Hiroshi Department 211

Claims (1)

[Scope of Claims] 1. A method for producing a bead-shaped cyclodextrin polymer, which comprises dispersing Cyfrobukis IJ, which has been polymerized to the extent that it will not become insolubilized, in a cross-linking agent and reacting with it to make it into an insoluble polymer. . 2. The manufacturing method according to claim 1, wherein the crosslinking agent is epichlorohydrin and a jepoxy compound.