JPS63314201A - Method for immobilizing cyclodextrin - Google Patents

Abstract

PURPOSE:To immobilize cyclodextrin in a relatively short time and with good efficiency, by first reacting a specified cross-linked copolymer having epoxy rings with hydrochloric acid, and then reacting cyclodextrin with the treated copolymer. CONSTITUTION:After treating a cross-linked copolymer, which has glycidyl monovinyl ester or glycidyl monovinyl ether monomer units, with hydrochloric acid to open epoxy rings thereof, cyclodextrin is reacted with the treated copolymer. It is desirable to use a diester or a triester of acrylic acid or methacrylic acid as the cross-linking agent in an amount based on the total monomer used (degree of cross-linking) of 5-60wt.%.

Description

[Detailed description of the invention] <Industrial field of application> The present invention removes fillers or catalysts used in chromatographic separation of each component from a liquid in which multiple components are dissolved, or hydrophobic substances in the liquid. The present invention relates to a method for producing a cyclodextrin-immobilized polymer used for commercial purposes, etc., and relates to a method for efficiently immobilizing cyclodextrin on a polymer in a short time.

<Prior art> Cyclodextrin contains 6 or more units of glucose and α-1.
4-linked cyclic oligosaccharide with 6.7.8 glucose units
These are particularly well known, and there are many published documents regarding their applications. All of these application examples utilize the selective inclusion ability due to the fact that the inside of the cyclodextrin ring is hydrophobic and the size of this ring is determined by the amount of glucose units. They are used as agents, catalysts, to mask off-tastes and odors in foods, to retain volatile substances, and to solubilize poorly soluble substances.

It is easy to predict that such selective inclusion ability would be an effective means for separating and extracting hydrophobic substances. It is difficult to separate the clathrate from the system and to separate the clathrate from the cyclodextrin.

If cyclodextrin is solidified while maintaining its inclusion ability, it can be packed into a column and its components can be separated, recovered, and removed by adsorption and desorption operations similar to ion exchange resins and activated carbon, or by chromatography operations. It's easy to do.

Therefore, various methods have been attempted to immobilize cyclodextrin, but the utilization rate of immobilized cyclodextrin is low, and the base polymer on which cyclodextrin is immobilized adsorbs hydrophobic substances. Furthermore, they were unsuitable for effective industrial use, as they had insufficient selectivity and required a great deal of cost to manufacture.

For example, a solid cyclodextrin polymer is obtained by crosslinking cyclodextrin with shrimp chlorohydrin, aldehyde, and a jepoxy compound using a method similar to that used for dextran gel, which has been known for a long time.This is then suspension polymerized in liquid paraffin. However, in this case, if the degree of crosslinking is increased to make it strong enough to be packed in a column, diffusion of the solute will be hindered and the reaction rate will be extremely slow. On the other hand, if the degree of crosslinking is such that rapid diffusion of solute occurs, the cyclodextrin polymer becomes too soft and unsuitable as a column packing material.

Instead of crosslinking cyclodextrins with each other as described above, a method has also been proposed in which cyclodextrins are bonded directly or via a spacer to a parent polymer prepared in advance. Among these, those whose base material is a copolymer of styrene and dinylbenzene are hydrophobic in nature, so they non-selectively adsorb hydrophobic substances in the solution to be treated. Therefore, in the desorption or elution step, the hydrophobic substances selectively captured by the cyclodextrin are undesirably contaminated with the hydrophobic substances adsorbed by these parent bodies.

In addition, as a method for preventing the adsorption of impurities by this matrix, it has been proposed (Japanese Patent Publication No. 15561/1982) to make the matrix itself a highly hydrophilic polymer. In other words, methacrylic acid ester having an epoxy ring, for example,
Cyclodextrin is immobilized on a polymer that uses glycidyl methacrylate as one of the monomers.

In this method, the epoxy ring opens simultaneously with the reaction with cyclodextrin to become an alcoholic hydroxyl group, yielding a cyclodextrin-immobilized polymer with high hydrophilicity and therefore less simultaneous adsorption of impurities.

However, when we actually tried this proposed method, that is, directly bonding the epoxy rings of the base polymer with cyclodextrin in the presence of an alkaline aqueous medium through a ring-opening reaction, we found that a sufficient amount of cyclodextrin was added to the base polymer. The cyclodextrin binding requires a long reaction time, and the cyclodextrin actually bound is only a fraction of the initial amount, so the excellent inclusion ability of cyclodextrin can be utilized for various purposes. It became clear that there were problems in terms of economic efficiency.

<Problems to be Solved by the Invention> The present invention solves the above-mentioned drawbacks of the conventionally proposed method of immobilizing cyclodextrin on a polymer using methacrylic acid having an epoxy ring as one of the monomers, and The present invention relates to a method for immobilizing cyclodextrin, which aims to immobilize cyclodextrin efficiently in a relatively short time.

Means for Solving the Problems> The technical means of the present invention for achieving the above object is to open the epoxy ring by treating a crosslinked copolymer having glycidyl monovinyl ester or glycidyl monovinyl ether as one of the monomer components with hydrochloric acid. This is a method for immobilizing cyclodextrin, which is characterized in that it is bonded to cyclodextrin after ringing.

Effect〉 The method of the present invention will be explained in detail below.

The crosslinked copolymer using glycidyl monovinyl ester or glycidyl monovinyl ether as one of the monomer components used in the present invention can be produced by a known method. The glycidyl monovinyl ester used as a monomer can be a glycidyl ether of a monovinyl carboxylic acid having 3 to 12 carbon atoms, and the glycidyl monovinyl ether can be a glycidyl ether of a monovinyl alcohol having 3 to 12 carbon atoms. It is desirable to have a small amount, and it is preferable to use glycidyl methacrylate, glycidyl acrylate, allyl glycidyl ether, and the like.

Aromatic divinyl compounds such as divinylbenzene, divinyltoluene, and divinylnaphthalene can also be used as crosslinking agents, but they are not suitable for making the base polymer hydrophilic, and diesters or triesters of acrylic acid or methacrylic acid are preferable. desirable. Specifically, those falling into this category include ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate, propylene glycol dimethacrylate, and trimethylolpropane triacrylate.

The amount of the crosslinking agent to be used is 5 to 60% by weight as a ratio (degree of crosslinking) to the total monomers, and preferably 20 to 60% if the base polymer is to be macroporous.

Since the solubility of these monomers in water is sufficiently low, suspension polymerization in an aqueous medium is convenient for the polymerization reaction.

A polymerization initiator such as benzoyl peroxide or azobisisobutylnitrile is added to a mixed solution of monomers, and the mixture is suspended in water in which a dispersant has been dissolved in advance while stirring. By heating to the polymerization initiation temperature while stirring, a spherical polymer is obtained. This polymer is of a so-called gel type and has no macropores. In the case of the gel-type polymer, the degree of crosslinking is preferably low in order to facilitate the diffusion of cyclodextrin into particles during immobilization of cyclodextrin or the diffusion of solute when using the polymer after immobilization. . However, when the degree of crosslinking is lowered, there is a problem in that the physical stability is lowered accordingly. Therefore, it is physically stable,
Macroporous polymers are desirable for smooth immobilization of cyclodextrin and diffusion of solutes.There are various methods for producing macroporous polymers, but in all cases, the monomer solution is added to the monomer solution before polymerization. It can be produced in the same manner as the gel type described above, except that additives are added. Various additives are used, but they can be roughly divided into three types. The first is one that dissolves the monomer solution well and also swells the copolymer, and is usually called a swelling agent. The second is called a precipitant, which dissolves the monomer but does not swell the copolymer. The third is a non-crosslinked linear polymer. Combination methods of these methods are also commonly used, and both methods are well known.

In the copolymer thus obtained, although a very small portion of the epoxy rings of the glycidyl monovinyl ester or glycidyl monovinyl ether used as a monomer are lost due to ring opening and crosslinking, usually 70% or more of the epoxy rings are unopened. It remains as is.

This eboxy ring has relatively high reactivity, so various functional groups can be introduced into it. It is also known to introduce a compound having an alcoholic hydroxyl group, and the reaction is exactly the same as when shrimp chlorohydrin or a jepoxy compound is used to crosslink cyclodextrins with each other.

However, in the known method of directly reacting cyclodextrin with the epoxy ring of the polymer, the examples described later,
Even after a long reaction time as shown in the comparative example, only a very small amount of cyclodextrin reacted, and when the base polymer was a gel type, the prepared gel bore could not be used effectively due to the low degree of crosslinking. , and in the case of macroporous polymers, their large surface area cannot be utilized effectively.

In the present invention, by treating the copolymer having an epoxy ring produced by the method described above with hydrochloric acid for 30 minutes to 1 hour, for example, as shown in the structural formula of formula (1) or formula (2), Open the epoxy ring.

Hs -cHt-c-...(1) C00CH! -CHoH-CHICβ -CHt-C- ・ ・ ・ (2) CHt OCHz CHOH-CHtCml Formula (1) shows the case of a copolymer using glycidyl methacrylate, which is a type of glycidyl monovinyl ester, as a monomer, and ( Formula 2) shows the case of a copolymer using allyl glycidyl ether, which is a type of glycidyl monovinyl ether, as a monomer.

When the epoxy ring is opened by treating the copolymer with hydrochloric acid in this manner, the copolymer has a hydroxyl group and a chloromethyl group. It has been known for a long time that the chloromethyl group is highly reactive, and the hydroxyl group generated here is much more hydrophilic than the original epoxy group, causing the copolymer to swell and bond to the cyclodextrin copolymer. Penetration into the interior can occur extremely quickly.

In the present invention, the cyclodextrin is bonded to the copolymer with the epoxy ring opened in this way, but the reaction between the cyclodextrin and the copolymer is carried out by adding the copolymer treated with hydrochloric acid in this way to the alkaline state of the cyclodextrin. It may be added to an aqueous solution and heated. As described above, the present invention requires one additional manufacturing step compared to the conventional immobilization method in which cyclodextrin is directly reacted with a copolymer having an epoxy ring, but the added step is a simple step, and the use of cyclodextrin It is clear that this method is far superior to the conventional method when comparing the high ratio and the large inclusion ability per unit amount of cyclodextrin-immobilized polymer of the product.

EXAMPLES The present invention will be explained in more detail with reference to Examples below.

Reference Example 1 (Production of copolymer) 50 g of glycidyl methacrylate, 50 g of ethylene glycol dimethacrylate, 100 g of toluene.

A mixed solution of 1 g of benzoyl peroxide was added to water in step 11 in which 1.5 g of polyvinyl alcohol was dissolved, heated to 70° C. with stirring, and kept for 8 hours to polymerize. After cooling, the resulting spherical copolymer was filtered off, washed with water, methanol, and dried.

Example 1 (Hydrochloric acid treatment and immobilization of cyclodextrin) Of the copolymer obtained in Reference Example 1, 10 g was heated at 60°C for 1 hour in 80 ml of a 14% hydrochloric acid aqueous solution with stirring, washed with water, and then dried. .

5 g of this hydrochloric acid-treated copolymer was dissolved in a 1N soda solution containing 13 g of β-cyclodextrin.
In addition to 5 ml, the 0 reaction product was reacted at 60° C. for 3 hours with stirring and was washed and dried.

β determined from the difference between the total amount of unreacted β-cyclodextrin, including that contained in wastewater during washing, and the amount charged.
- The amount of immobilized cyclodextrin was 0.33 g per 1 g of the copolymer of Reference Example 1.

Comparative Example 1 5 g of the copolymer obtained in Reference Example 1 was reacted with β-cyclodextrin under the same conditions as in Example 1 without being treated with hydrochloric acid. However, the reaction time was 8 hours. In this case, the amount of β-cyclodextrin fixed per 1 g of raw material copolymer was 0.08 g.

Example 2 25 ml of a solution of hesveridin dissolved in pure water at a concentration of 100 μl/l and each Ig of the β-cyclodextrin-immobilized polymer obtained in Example 1 and Comparative Example 1 (wet state) were mixed for 12 hours while stirring. The amount of adsorption of hesveridin was determined by contacting for a period of time. The results were as follows.

Hydrochloric acid treated 2.7mg/g-wet Untreated 0.73mg/g-wet Example 3 The copolymer produced in Reference Example 1 was used, and α-cyclodextrin was used as the cyclodextrin. An immobilized polymer was produced under exactly the same conditions as in Example 1. The amount of α-cyclodextrin immobilized was 0.41 g per gram of raw material copolymer, and the amount of hesperidin adsorbed measured under the same conditions as in Example 2 was 0.54 μ/g-wet.

<Effect> As is clear from the above examples, in the conventional immobilization method, only 3% of the cyclodextrin added for immobilization was bound to the copolymer, and the reaction time for the binding was 8 hours. In contrast, the immobilization method according to the present invention requires only 13% of the cyclodextrin added for immobilization.
can be bonded to the copolymer, and the reaction time for the bonding can also be shortened to 172 or less compared to conventional methods.

Furthermore, the amount of cyclodextrin that can be bound to the copolymer can be increased to more than four times that of the conventional method based on the weight of the copolymer.

Claims (1)

[Claims] A method for immobilizing cyclodextrin, which comprises treating a crosslinked copolymer having glycidyl monovinyl ester or glycidyl monovinyl ether as one of the monomer components with hydrochloric acid to open the epoxy ring, and then bonding cyclodextrin.