JP3069668B2 - Etherified cyclodextrin polymer - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

This invention relates to novel water-insoluble etherified cyclodextrin polymers.

2. Description of the Related Art A method for producing a water-insoluble cyclodextrin polymer or beads thereof from cyclodextrin using a crosslinking agent has been conventionally known. For example, Japanese Patent Publication No. 60-11961 discloses a method for producing a cyclodextrin polymer by dispersing cyclodextrin polymerized to such an extent that it is not insolubilized by epichlorohydrin in liquid paraffin, and then adding epichlorohydrin while maintaining the temperature at a predetermined temperature. JP-A-60-209
No. 24 discloses a method of forming a cross-linked polymer using epichlorohydrin, a diepoxy compound, a diisocyanate, an acrylamide derivative, or the like, or dispersing a cyclodextrin polymerized to such an extent that the cross-linking agent does not insolubilize in advance in the cross-linking agent. And a method for producing a water-insoluble cyclodextrin polymer.

The water-insoluble cyclodextrin polymer obtained as described above, for example, a water-insoluble β-cyclodextrin polymer crosslinked with epichlorohydrin, is effective for removing bitter components such as limonene and naringin in grapefruit juice. And it has been reported that the polymer used can be regenerated with an aqueous alkali solution (see, for example, J. Food. Sci., 53 , 516 (198).
8)). Regarding the etherification reaction of cyclodextrin in an aqueous system, a reaction of methylating cyclodextrin in an aqueous sodium hydroxide solution using dimethyl sulfate as a methylating agent is known (JP-A-63-41505).
No.).

[0003]

It is known that conventional water-insoluble cyclodextrin polymers selectively adsorb specific compounds, and the compounds adsorbed on the polymer are easily dissolved in water or an aqueous alkaline solution. In some cases, desorption of the compound can also be performed. However, in many cases, the compounds of interest are poorly soluble in water or aqueous alkaline solutions. For this reason, recovery of the compound adsorbed on the polymer,
Alternatively, when the desorption of the compound is to be completely carried out for the regeneration of the polymer, an organic solvent or an organic solvent-water mixed solvent is often required. Conventional water-insoluble cyclodextrin polymers are used in organic solvents or organic solvents-
Because the volume of the polymer shrinks extremely in a water mixed solvent, or a block is formed between the polymers,
The properties relating to polymer adsorption and desorption are significantly reduced.
Therefore, its use is also limited. The object of the present invention is to reduce the volume change even in an organic solvent or an organic solvent-water mixed solvent, not only water but also an organic solvent or an organic solvent-
It is an object of the present invention to provide a novel cyclodextrin polymer capable of performing selective adsorption and desorption of a compound using a water mixed solvent.

[0004]

SUMMARY OF THE INVENTION The present invention provides a water-insoluble cyclo.
Etherification of some hydroxyl groups of dextrin polymer
The etherification rate is 15 to 65%, preferably 40 to 65%.
Water-insoluble etherified cyclodextrin polymer
Offer.

The cyclodextrin polymer used in the present invention is a polymer composed of α-cyclodextrin, β-cyclodextrin and / or γ-cyclodextrin. The above cyclodextrin polymers may be used alone or as a mixture. Sugars, inorganic substances, etc. may be added to increase the strength of the polymer. As a crosslinking agent for forming a polymer, epichlorohydrin, a diepoxy compound, a diisocyanate, an acrylamide derivative and the like can be used.Epichlorohydrin is particularly preferred in consideration of easiness of operation and stability of the obtained cyclodextrin polymer against heat, alkali and the like. preferable. The shape of the cyclodextrin polymer is a bead,
The shape is not limited, such as crushed, film, etc.
Considering the easiness of operations such as separation and desorption, ease of use, and the like, beads are particularly preferred. The above cyclodextrin polymers have been known in the art, and their production methods are disclosed in, for example, JP-A-60-20924 and JP-B-60-11961. As the etherifying agent, generally used alkyl sulfates such as dimethyl sulfate, diethyl sulfate, dipropyl sulfate and the like are preferably used.

[0006] The etherified cyclodextrin polymer of the present invention comprises a water-insoluble cyclodextrin polymer and an etherifying agent, preferably in an aqueous solution of an alkali metal hydroxide having a concentration of 10% (weight / volume) or more, by adding the etherifying agent to cyclodextrin. To a reaction amount of preferably at least 10 times the molar equivalent. As the alkali metal, sodium is particularly preferred in consideration of the solubility in water and the ease of post-treatment.

The concentration of the aqueous solution of the alkali metal hydroxide is 1
The upper limit is not particularly limited as long as it is 0% by weight or more, but is preferably 30 to 40% by weight (hereinafter, when simply referred to as%, it indicates% by weight). The etherifying agent is at least 10-fold molar equivalent, preferably 50-120-fold molar equivalent, to cyclodextrin constituting the cyclodextrin polymer. The reaction temperature is not particularly limited as long as it is a temperature at which the cyclodextrin polymer does not substantially decompose. However, the reaction is preferably performed at about 0 to 10 ° C. Stirring during the reaction is not particularly necessary, but stirring to such an extent that the suspended polymer is substantially uniformly dispersed is preferable in terms of making the reaction uniform. The reaction time varies depending on the kind, concentration, reaction temperature and the like of the alkali metal hydroxide to be used, but if the reaction is carried out for about 7 to 20 hours, a desired etherified cyclodextrin polymer can be obtained.

The etherified cyclodextrin polymer of the present invention has an etherification ratio of 15 to 65%, preferably 4 to 65%.
0 to 65%. If the etherification rate is low, the volume shrinkage in an organic solvent-water mixed solvent is large, and the characteristics relating to adsorption and desorption are undesirably reduced. The higher the etherification ratio of the cyclodextrin polymer of the present invention is, the smaller the volume shrinkage in the organic solvent-water mixed solvent is, and the more preferable it is.

Table 1 shows the relationship between the volume change of the etherified cyclodextrin polymer in 50% acetonitrile and the degree of etherification. The change in volume of the polymer is represented by a volume ratio based on the case where the polymer is suspended in water.

Table 1 Relationship between Volume Change of Polymer and Etherification Ratio Etherification Ratio Volume change of polymer 0% 77% 22.8% 89% 44.6% 100% 55.6% 100% 63.9% 100 % The etherification rate in the present invention was measured by the following elemental analysis method. After sufficiently washing the cyclodextrin polymer and the etherified cyclodextrin polymer with water, washing with 50% acetone water and then sufficiently dehydrating with acetone, the mixture is placed in a vacuum drier at 2-3 × 10 ^-2 mmHg for 10 seconds.
It was dried at 0 ° C. for 24 hours. The etherification rate of the obtained dried product was measured under the following conditions. (1) CHN analysis Instrument name: CH-3 coder MT-3 type manufactured by Yanagimoto Seisakusho Combustion conditions: Sample decomposition furnace 930 ° C Oxidation furnace 850 ° C Reduction furnace 550 ° C Helium flow rate 180 ml / min Oxygen flow rate 20 ml / min Sample amount: 2-3 mg ( 2) O-decomposition Equipment name: HERAEUS RAPID fully automatic elemental analyzer Combustion conditions: Sample decomposition furnace 1140 ° C Fractionation tube 1140 ° C Working gas N ₂ / H ₂ (95/5 volume% mixed gas) Gas flow rate 70ml / min Detector Non-dispersive spectrometer (Binos) Sample amount: 1 to 10 mg (using a microbalance).

[0011]

The present invention will be described in more detail with reference to the following examples.

Reference Example Production of Water-Insoluble Cyclodextrin Polymer Powdered β-cyclodextrin (trade name: RINGDEX-B,
9 g of water was added to 10.0 g of Mercian Co., Ltd., and the mixture was shaken. To this, 10 ml of a 50% aqueous sodium hydroxide solution and 100 mg of sodium borohydride were added to form a uniform solution. 3 ml of epichlorohydrin was added dropwise over 15 minutes while stirring at a speed of, and after stirring for another 30 minutes, liquid paraffin 2 was added.
After adding 00 ml, the mixture was stirred at a speed of 1000 rpm and at 60 ° C. for 2 hours. The obtained cyclodextrin polymer was separated by filtration, washed with 100 ml of hexane three times and then with 100 ml of acetone three times to remove liquid paraffin and epichlorohydrin, and then washed with distilled water until the pH of the washing solution became neutral. Then, sodium hydroxide, sodium chloride and water-soluble components were removed. After washing the obtained cyclodextrin polymer with 50% acetone water, it is sufficiently dehydrated with acetone and dried at 80 ° C. for 24 hours.
13.8 g of a colorless and transparent β-cyclodextrin polymer
I got

[0013]

Example 1 1.6 g (1 mmol as β-cyclodextrin content) of the water-insoluble cyclodextrin polymer obtained in Reference Example was suspended in 12.5 ml (125 mmol) of a 40% (w / v) NaOH aqueous solution. Reaction temperature 0
At -10 ° C, 8.9 ml (94 mmol) of dimethyl sulfuric acid was gradually added dropwise, and the reaction was continued with stirring for further 15 hours. After the reaction, 3 ml (44 mmol) of concentrated aqueous ammonia was added, and the mixture was further stirred for 6 hours. The obtained water-insoluble methylated cyclodextrin polymer was sufficiently washed with water.
After sufficiently washing with acetone, acetone was distilled off and dried, and methylated cyclodextrin polymer 1.9 was obtained.
g was obtained.

Each of the water-insoluble cyclodextrin polymer obtained in the reference example and the methylated cyclodextrin polymer obtained in the present example was dried at 100 ° C. for 24 hours in a reduced pressure drier of 2-3 × 10 ⁻² mmHg. The methylation rate was measured by the elemental analysis method. The methylation rate of the hydroxyl group of the methylated cyclodextrin polymer was 44.6%.

[0015]

Example 2 1.6 g (1 mmol as β-cyclodextrin content) of the water-insoluble cyclodextrin polymer obtained in Reference Example was suspended in 12.0 ml (60 mmol) of a 20% (w / v) aqueous NaOH solution. Reaction temperature 0
At 10 ° C., 0.95 ml (10 mmol) of dimethyl sulfate was gradually added dropwise, and the reaction was continued with stirring for further 15 hours. After the reaction, 1 ml (15 mmol) of concentrated aqueous ammonia was added, and the mixture was further stirred for 6 hours. The obtained water-insoluble methylated cyclodextrin polymer was sufficiently washed with water.
After sufficiently washing with acetone, acetone was distilled off and dried, and methylated cyclodextrin polymer 1.8 was obtained.
g was obtained.

Each of the water-insoluble cyclodextrin polymer obtained in the reference example and the methylated cyclodextrin polymer obtained in the present example were dried at 100 ° C. for 24 hours in a reduced pressure drier of 2-3 × 10 ⁻² mmHg. The methylation rate was measured by the elemental analysis method. The methylation rate of the hydroxyl group of the methylated cyclodextrin polymer was 22.8%.

[0017]

Example 3 1.6 g (1 mmol as β-cyclodextrin content) of the water-insoluble cyclodextrin polymer obtained in Reference Example was suspended in 14.0 ml (140 mmol) of a 40% (w / v) aqueous NaOH solution. Reaction temperature 0
At −10 ° C., 13.3 ml (140 mmol) of dimethyl sulfuric acid was gradually added dropwise, and the reaction was further continued with stirring for 15 hours. After the reaction, 10 ml (150 mmol) of concentrated aqueous ammonia was added, and the mixture was further stirred for 6 hours. The obtained water-insoluble methylated cyclodextrin polymer was sufficiently washed with water. After sufficiently washing with acetone, the acetone was distilled off and dried to obtain 1.9 g of a methylated cyclodextrin polymer.

The water-insoluble cyclodextrin polymer obtained in the reference example and the methylated cyclodextrin polymer obtained in the present example were each dried at 100 ° C. for 24 hours in a vacuum drier of 2-3 × 10 ⁻² mmHg. The methylation rate was measured by the elemental analysis method. The methylation rate of the hydroxyl group of the methylated cyclodextrin polymer was 55.6%.

[0019]

Example 4 1.4 g of the cyclodextrin polymer obtained in Reference Example and 1.7 g of the methylated cyclodextrin polymer obtained in Example 1 were suspended in 50 ml of water in a 100 ml Erlenmeyer flask. After extracting water with a pipette, about 50 ml of various organic solvents shown in Table 2 was added to each polymer, and the mixture was shaken at room temperature for 30 minutes. The shaken organic solvent was extracted, and about 50 ml of the same organic solvent was newly added, followed by shaking again for 30 minutes. After the same operation was further repeated 10 times, the solvent was completely replaced, and the volume of the polymer after the replacement was measured. Table 2 shows the measurement results.

[0020] Table 2 volume change cyclodextrin methylated Shikurodeki polymer stringent polymer water 100% 100% methanol 37% polymer * 82% Ethanol 38% * 59% acetonitrile 20% * 73% 35% acetone * 70% 1,4 Dioxane 31% * 97% Dimethylformamide 100% 100% 50% Ethanol 88% 100% 80% Ethanol 52% 99% 50% Acetonitrile 77% 100% Note: * The polymer has changed from colorless and transparent to white. And the volume ratio based on the suspension in water.

[0021]

Example 5 1.4 g of the cyclodextrin polymer obtained in Reference Example and 1.7 g of the methylated cyclodextrin polymer obtained in Example 3 were suspended in 50 ml of water in a 100 ml Erlenmeyer flask. After extracting water with a pipette, about 50 ml of various organic solvents shown in Table 3 was added to each polymer, and the mixture was shaken at room temperature for 30 minutes. The shaken organic solvent was extracted, and about 50 ml of the same organic solvent was newly added, followed by shaking again for 30 minutes. After the same operation was further repeated 10 times, the solvent was completely replaced, and the volume of the polymer after the replacement was measured. Table 3 shows the measurement results.

[0022] Table 3 volume changes cyclodextrin methylated Shikurodeki polymer stringent polymer water 100% 100% methanol 37% polymer * 92% Ethanol 38% * 64% acetonitrile 20% * 86% 35% acetone * 79% 1,4 Dioxane 31% * 99% Dimethylformamide 100% 100% 50% Ethanol 88% 100% 80% Ethanol 52% 100% 50% Acetonitrile 77% 100% Note: * The polymer changed from colorless and transparent to white. And the volume ratio based on the suspension in water.

[0023]

Example 6 1.4 g of the cyclodextrin polymer obtained in Reference Example and 1.7 g of the methylated cyclodextrin polymer obtained in Example 1 were each suspended in 50 ml of water in a 100 ml Erlenmeyer flask. After extracting water with a pipette, about 14 mg of p-
A solution in which xylene was dissolved in 100 ml of water was added, and the mixture was shaken at room temperature for 1 hour. After shaking, each polymer was added to 2.1
A glass column of cm × 10 cm was packed and washed with 10 ml of water. 95% methanol was passed through each polymer to which p-xylene was adsorbed. V. = 6,
Fractionation for each bed was performed. Solution of p-xylene, solution after shaking, washing solution of polymer and 95
The eluent of% methanol was subjected to gas chromatography to determine the amount of p-xylene. Table 4 shows the measurement results.

[0024] Table 4 Recovery cyclodextrin methylated Shikurodeki polymer stringent polymeric adsorbent p- xylene 10.635mg 10.505mg elution of p- xylene at each polymer 1 bed 0.917mg 1.087mg 2 bed 5.981mg 8.096mg 3 Bed 0.136 mg 1.020 mg 4 bed 0.091 mg 0.095 mg 5 bed 0.040 mg 0.047 mg 6 bed 0.026 mg 0.027 mg 7 bed 0 mg 0 mg 8 bed 0 mg 0 mg p-xylene recovery 98.66% 7%

According to the present invention, there is provided an etherified cyclodextrin polymer in which the volume shrinkage in an organic solvent or an organic solvent-water mixed solvent is remarkably reduced.
Further, according to the present invention, there is provided an etherified cyclodextrin polymer capable of easily desorbing a compound which is hardly soluble in water, and a method for producing the same. For example, when desorbing (eluting) a compound that is hardly soluble in water such as p-xylene, in a conventional cyclodextrin polymer, if desorption (elution) is performed using, for example, methanol as an organic solvent, the volume shrinkage of the polymer will occur. -Whitening progresses and sufficient desorption (elution) cannot be performed. On the other hand, in the case of the etherified cyclodextrin polymer of the present invention, desorption (elution) can be easily carried out without using an organic solvent or an organic solvent-water mixed solvent without causing volume shrinkage or blocking.

────────────────────────────────────────────────── ─── Continued on the front page (51) Int.Cl. ⁷ Identification code FI // C08G 18/32 C08G 65/32 (72) Inventor Kazuaki Harada 4-424 Matsushiro 4-chome, Building No. 305, 4-424, Matsushiro, Tsukuba-shi, Ibaraki (56) References JP-A-64-36603 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) C08B 37/16

Claims (2)

(57) [Claims] 1. The water of a water-insoluble cyclodextrin polymer.
A part of the acid groups is etherified, and the etherification ratio is 15 to 65.
% Water-insoluble etherified cyclodextrin polymer. 2. An etherification ratio of 40 to 65%.
1. The water-insoluble etherified cyclodextrin polymer of 1.