JP2544166B2 - Method for removing α-cyclodextrin - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for efficiently removing α-cyclodextrin from various cyclodextrin mixtures containing α-cyclodextrin.

"Conventional technology and problems" Cyclodextrin has functions such as stabilizing unstable substances, preventing volatilization of volatile substances, masking offensive odors, solubilizing poorly soluble / insoluble substances, and catalyzing chemical reaction. Are being studied.

It is believed that these functions are achieved by the inclusion effect of lipophilic substances being encapsulated in the steric cavities of cyclodextrin.

Cyclodextrin includes α-cyclodextrin in which 6 glucoses are bound in a cyclic manner, and β-cyclodextrin in which 7 glucoses are bound in a cyclic manner
-Cyclodextrin, γ-cyclodextrin having 8 cyclic bonds, δ-cyclodextrin having 9 or more cyclic bonds, ε-cyclodextrin, etc. are known. Further, α-, β-, G ₁ -α- cyclodextrin conjugated with one glucose to cyclodextrin of γ- like, G _{1-.beta.-cyclodextrin,} G _1-.gamma.-
Glucosyl cyclodextrin in cyclodextrin such as, G _{2-.alpha.-conjugated} two maltose glucose
Maltosyl cyclodextrins such as cyclodextrin, G ₂ -β-cyclodextrin, G ₂ -γ-cyclodextrin, G ₃ -α-cyclodextrin and G ₃ -β-cyclo to which maltotriose of 3 glucose is bound. Maltotriosyl cyclodextrins such as dextrin and G ₃ -γ-cyclodextrin, G ₁ , G _1- , G ₁ and G _{2 in which} two or more cyclodextrins are bound with maltotriosyl cyclodextrin, glucosyl group, maltosyl group and maltotriosyl group. -,
Branched cyclodextrins such as G ₂ and G ₂ − are known.

As a method for producing these cyclodextrins, an enzyme (cyclodextrin glucanotransferase) is allowed to act on starch to form α-cyclodextrin and β-cyclodextrin.
There are methods for obtaining cyclodextrins such as cyclodextrin and γ-cyclodextrin, etc., and dexpearl K, dexpearl L, celldex CH, lindex-P, toyoderin-P and the like are commercially available. These are α
-Cyclodextrin, β-cyclodextrin,
It is a mixture of various cyclodextrins such as γ-cyclodextrin and dextrin, and a method for obtaining various cyclodextrin mixtures of α-cyclodextrin-rich and β-cyclodextrin-rich by a production method, for example, selection of an enzyme, has been developed. There is.

 Table 1 shows an example of composition analysis of typical commercial products.

Further, as a method for producing a branched cyclodextrin, a reverse reaction of pullulanase is used to bind maltose to α-1,6 to cyclodextrin to produce a branched cyclodextrin such as maltosyl cyclodextrin, which has a high concentration. A method for producing maltosyl cyclodextrin by allowing a thermostable pullulanase produced by Bacillus sp. To act on a solution of maltose and cyclodextrin for a long time at high temperature.A method for producing maltosyl cyclodextrin is used. Α
There is a method of producing maltotriosyl cyclodextrin by bonding to 1,6 bonds, and isoelite and the like are commercially available. Commercially available branched cyclodextrins produced by these methods are non-branched cyclodextrins such as α-cyclodextrin, β-cyclodextrin and γ-cyclodextrin, branched-α-cyclodextrin, branched-β-cyclodextrin, branched. −γ−
It is a mixture of cyclodextrin, glucose, maltose, maltotriose and dextrin. Table 2 shows an example of composition analysis of typical commercial products.

As described above, commercially available cyclodextrins and branched cyclodextrins are mixtures of various cyclodextrins.

On the other hand, many attempts have been made to produce cyclodextrin with high purity. As an example, a method combining an ultrafiltration membrane and a reverse osmosis membrane has been developed. Briefly, the α-, β-, γ-cyclodextrin and dextrin mixture produced in the reaction vessel is passed through an ultrafiltration membrane and sent to a reverse osmosis membrane. Since unreacted dextrin other than cyclodextrin has a large molecular weight and cannot pass through the ultrafiltration membrane, it is returned to the reaction tank and reused as a raw material for cyclodextrin production. By adding a small amount of debranching enzyme to the reaction vessel, all starch is converted to cyclodextrin and concentrated on the reverse osmosis membrane. The concentrated cyclodextrin solution is sent to a crystallization tank to crystallize β-cyclodextrin having low solubility. The mother liquor is again concentrated in a reverse osmosis membrane and sent to a crystallization tank. By this repetitive operation, crystals are obtained in the order of β-, α-, and γ-cyclodextrin, and high-purity α- and γ-cyclodextrin are obtained by recrystallization.

Thus, obtaining a highly pure cyclodextrin requires a lot of labor and labor, and particularly α- and γ-cyclodextrin, which have high solubility in water and are difficult to decompose, are expensive, and various cyclodextrins and dextrins Compared with the mixture, α-cyclodextrin was several tens of times higher than γ
Cyclodextrins are more expensive.

Also, regarding cyclodextrin containing branched cyclodextrin, the solubility of various cyclodextrins in water is similar and the compatibility effect is combined, so it is very difficult to isolate various highly pure cyclodextrins by column chromatography etc. It requires sophisticated separation technology and is very expensive. Table 3 shows the solubility of various cyclodextrins in water, including branched cyclodextrins.

There is generally a selectivity between these cyclodextrins (hosts) and the substances to be incorporated (guests), which are stabilized when the size of the cyclodextrin cavity and the steric size of the guest molecules match, and are easily included. It is believed that. In addition, the inclusion of the guest often changes the solubility of the guest, and the poorly water-soluble substance is solubilized. This change in solubility is also related to the type of cyclodextrin. In many cases, α-cyclodextrin forms a soluble inclusion complex and β-cyclodextrin forms a poorly soluble inclusion complex. Other functions of stabilizing destabilizing substances, preventing volatilization of volatile substances, masking offensive odors, and catalyzing functions of chemical reactions are also expected to be related to the types of cyclodextrins. That is, depending on the expression of the desired function, the cyclodextrins of each other, for example, α-cyclodextrin and β-cyclodextrin, or α-cyclodextrin and various types of branched cyclodextrins often inhibit each other's functions. In such a case, it is ideal to use a high purity cyclodextrin alone, but as described above, the price is extremely high and the practicality is poor.

"Means for solving the problem" In view of the above circumstances, the present inventors have diligently studied a method for inexpensively removing α-cyclodextrin from various cyclodextrin mixtures, and as a result, various types containing α-cyclodextrin. It was found that various cyclodextrin mixtures having a very low α-cyclodextrin concentration can be obtained by mixing the cyclodextrin mixture and monoglyceride in the presence of water and removing the resulting insoluble portion. .

That is, the present invention comprises a method for removing α-cyclodextrin, which comprises mixing various cyclodextrin mixtures containing α-cyclodextrin with monoglyceride in the presence of water, and removing the insoluble portion produced. To do.

The various cyclodextrin mixtures used in the present invention may be all those containing a certain amount of α-cyclodextrin.

For example, α-obtained by reacting starch with an enzyme (cyclodextrin glucanotransferase)
Cyclodextrin, β-cyclodextrin, γ
-Cyclodextrin, a mixture of cyclodextrins in which 9 or more glucose molecules are cyclically linked, a mixture of dextrins, etc., a method utilizing the reverse reaction of pullulanase, Bacillus s
p-produced thermostable pullulanase at a high temperature for a long time, or a method utilizing the reverse reaction of isoamylase α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, various branched cyclodextrins (G ₁ −α−, G ₂ −α−, G ₃ −α
−, G ₁ −β−, G ₂ −β−, G ₃ −β−, G ₁ −γ−, G ₂ −γ
-, G _{3-.gamma.-like)} dextrin, glucose, maltose, a mixture of maltotriose acids are used.

The monoglyceride used in the present invention is not particularly limited, and examples thereof include saturated monoglycerides such as monopalmitin, monostearin and monolaurin, unsaturated monoglycerides such as monoolein and monolinol, and mixtures thereof. Further, monoglycerides include those having a fatty acid group at the 1-position of glycerin and those having a fatty acid group at the 2-position as positional isomers, and any of them can be used. Monoglyceride does not dissolve in water, but various phase diagrams can be formed by changing the mixing ratio with water and further changing the temperature.

For example, in the case of saturated monoglyceride, it is a solid (β-crystal) at room temperature, it takes an α-gel structure when the temperature rises, and the neat structure, lamé structure, Dispersion structure, and Viscous Isotropi structure depending on the ratio with water when the temperature further rises.
It adopts c structure, Fluid Isotropic structure, etc.

In the present invention, the mixture of various cyclodextrin mixtures containing α-cyclodextrin and monoglyceride may have any structure of monoglyceride, but preferably in a molten state, that is, α-gel structure, neat structure, lamé structure. , Dispersion structure, Viscou
s Isotropic structure, Fluid Isotropic structure, etc.

In the present invention, various cyclodextrin mixtures containing α-cyclodextrin and monoglyceride are mixed in the presence of water to remove the insoluble portion produced, but this removal is performed by filtration under reduced pressure, centrifugation, pressurization. It is carried out by a general separation means such as filtration or membrane separation. The undissolved portion in this case may be unreacted monoglyceride, a reaction product of α-cyclodextrin and monoglyceride, or the like.

The aqueous phase from which the insoluble portion has been removed is, as it is, or after being dried and powdered by a conventional method, or after being mixed with a monoglyceride sparingly soluble solvent such as excess water to precipitate the dissolved monoglyceride and to separate it, It is used as it is or after being dried and powdered. Alternatively, before removing the insoluble portion, it is mixed with an excess water or other monoglyceride sparingly soluble solvent to precipitate dissolved monoglyceride, and then the insoluble portion is removed as it is, or it is dried and powdered before use. It

[Operation / Effect] According to the present invention, various cyclodextrin mixtures containing almost no α-cyclodextrin can be produced at low cost from various cyclodextrin mixtures containing α-cyclodextrin. This can be understood from the liquid chromatographic analysis results shown in Table 4 of the examples.

Various cyclodextrin mixtures containing almost no α-cyclodextrin obtained by the present invention are α-cyclodextrin mixtures.
It is particularly effectively used when cyclodextrin inhibits the function of other various cyclodextrins by inclusion.

"Examples" Hereinafter, the present invention will be described in more detail based on examples, but the present invention is not limited thereto.

Example 1 Isoeryte powder product [manufactured by Shimizu Minato Sugar Co., Ltd., total cyclodextrin content 80%] 1 kg water 1 kg, monostearin [manufactured by Riken Vitamin Co., monostearin content 98%] 1
2.5 g was added, and the mixture was mixed with a TK homomixer [made by Tokushu Kika Kogyo KK] for 30 minutes at a temperature of 80 to 90 ° C.

Example 2 The procedure of Example 1 was repeated, except that 25 g of monostearin was used.

Example 3 The procedure of Example 1 was repeated except that 37.6 g of monostearin was used.

Example 4 The procedure of Example 1 was repeated, except that 62.6 g of monostearin was used.

Example 5 In Example 1, instead of monostearin, EMergy MS [manufactured by Riken Vitamin Co., monostearin 70%,
Monopalmitin 30%] 100 g was used in the same manner as in Example 1.

Example 6 Example 1 was repeated except that 100 g of monoolefin (purity 98%) was used instead of monostearin.

Example 7 Dixipearl granules (K-50, manufactured by Shimizu Minato Sugar Co., Ltd., total cyclodextrin content 50%) 1 kg, water 1 kg, monostearin (same as Example 1) 155 g were added, and the temperature was 80-90 ° C. Mix for 30 minutes with a TK homomixer.

After cooling the mixtures obtained in Examples 1 to 7 at room temperature, the mixture was centrifuged to remove the insoluble portion to obtain an aqueous phase.

After filtering this aqueous phase with a 0.2 μm filter, liquid chromatography analysis was performed under the following conditions.

Liquid chromatographic analysis conditions: Device: JASCO 880-PV Column: Aibar Cichrosorb NH ₂ (5μ) Eluent: Acetonitrile: Water = 60:40 Elution rate: 1 ml / min Detector: Shodex SE-61 Various cyclodextrin analysis results The results are shown in Table 4. For comparison, the results of analysis of the raw materials DEXIPEARL K50 and isoelite are also shown.

As shown in Table 4, various cyclodextrin mixtures containing α-cyclodextrin were mixed with monoglyceride in the presence of water, and the resulting insoluble portion was removed to obtain various types of α-cyclodextrin-free Cyclodextrin can be obtained.

Under the liquid croft analysis conditions shown in the table, α
-Glucose, maltose, cyclodextrin
Maltotriose, etc. are also likely to be eluted in duplicate in the β-cyclodextrin part, such as maltotriose and maltotetraose, and the actual values of α-cyclodextrin and β-cyclodextrin are further increased. It is expected to be low.

As described above, according to the present invention, various cyclodextrin mixtures containing almost no α-cyclodextrin can be easily and inexpensively produced from various cyclodextrin mixtures.

Claims (3)

(57) [Claims] 1. A method for removing α-cyclodextrin, which comprises mixing various cyclodextrin mixtures containing α-cyclodextrin with monoglyceride in the presence of water to remove the insoluble portion formed. 2. The removal method according to claim 1, wherein the monoglyceride is a saturated monoglyceride, an unsaturated monoglyceride, or a mixture thereof. 3. The removal method according to claim 1 or 2, wherein various cyclodextrin mixtures containing α-cyclodextrin and monoglyceride are mixed in a temperature range in which each monoglyceride is dissolved.