JPH0475849B2 - - Google Patents

Description

[Detailed Description of the Invention] Industrial Application Field The present invention is applicable to chemicals, especially pharmaceuticals, agricultural chemicals, insecticides,
This invention relates to a novel montmorillonite and methylated cyclodextrin-based crystalline composite used as microcapsules for herbicides, fillers for gel chromatography, etc., and a method for producing the same.

Conventional technology Conventionally, cyclodextrin-based compounds have been used for microencapsulation to stabilize chemically unstable substances, especially pharmaceuticals, pesticides, herbicides, etc., by utilizing their molecular inclusion ability and catalytic ability. It is used as a solubilizing agent for poorly soluble substances, a packing material for column chromatography, etc. It has also attracted attention as an enzyme model, and attempts are being made to improve its functionality by introducing special functional groups and use it as an artificial enzyme.

In order to improve the functionality of cyclodextrin, conventional methods have been to introduce functional groups into cyclodextrin or to make it into a polymer.

The present inventor previously developed montmorillonite having a layered structure using α- and γ-cyclodextrins.
By immersing and reacting in an aqueous solution of mono-(6-β-aminoethylamino-6-deoxy)-β-cyclodextrin, a crystalline composite containing cyclodextrin molecules between layers was developed (Japanese Patent Application Laid-Open No. 60−166213).

However, the former two produce complexes only using highly concentrated aqueous solutions, and the latter modified dextrin is difficult to synthesize in large amounts with good yield, making it impossible to mass-produce the complex. There was a drawback.

OBJECT OF THE INVENTION The present invention aims to overcome the drawbacks of the conventional method for producing crystalline composites, and its purpose is to provide a crystalline composite of montmorillonite-cyclodextrin that is suitable for various molecular inclusions and can be mass-produced. Our goal is to provide the following.

Composition of the Invention As a result of further intensive research to achieve the above object, the present inventor has found that a highly crystalline complex can be obtained from a low concentration aqueous solution of methylated cyclodextrin in which the hydroxyl groups of α and β-cyclodextrins are substituted with methyl groups. It has been found that it can be produced with high yield. The present invention was completed based on this knowledge.

The gist of the present invention is the general formula (X, Y) _2~3 Z ₄ O ₁₀ (OH) ₂ mH ₂ O (W) _n (where X is Al, Fe (), Mn () and Cr
Trivalent metal selected from (), Y is Mg, Fe (),
Divalent metal selected from Mn () and Ni, Z is Si
Alternatively, montmorillonite has a layered structure represented by Al, W is a metal selected from Cu (), K, Na, and Ca, and m represents the number of water molecules), and a methylated cyclodextrin compound is placed between the layers. or in crystalline complexes consisting of those present together with other organic molecules.

Methylated cyclodextrin and montmorillonite used in the present invention are both compounds having molecular inclusion ability. Molecular inclusion ability means that there is a cavity of an appropriate size inside a three-dimensional or two-dimensional structure formed by bonding atoms or molecules, and other molecules can be incorporated into the cavity to form a specific crystal structure. It has the ability to

For example, cyclodextrin, which is a cyclic polymer of D-glucose, has a cylindrical cavity in the center with a diameter of 5 to 8 Å and a depth of 8 Å, and has a catalytically active alcohol group in the side chain, and has inclusion ability and catalytic activity. He has the ability.

Moreover, the montmorillonite represented by the above general formula has a layered structure and has inclusion ability. By introducing methylated cyclodextrin alone or together with other organic molecules between the layers of this montmorillonite to form a composite, it has two inclusion lattices, one layered and one cylindrical. It can be obtained by improving substrate specificity and properties as a gel filtration material, and is useful as a microencapsulating agent for chemicals, especially pharmaceuticals, agricultural chemicals, insecticides, herbicides, etc., and as a packing material for gel chromatography. It was.

In the present invention, the methylated cyclodextrin to be complexed with montmorillonite refers to α, β, and γ cyclodextrin consisting of 6, 7, and 8 D-glucose units, with some or all of the primary and secondary hydroxyl groups OH replaced with methoxy groups. - It is a derivative substituted with _OCH3 .

The composite of the present invention can be produced by mixing methylated cyclodextrin alone or an aqueous solution containing other organic molecules with montmorillonite powder and holding the mixture for a certain period of time. For example, in the case of a binary composite of montmorillonite and methylated cyclodextrin, 1 g of montmorillonite powder is mixed with an aqueous solution containing 1 to 10 mmol of methylated cyclodextrin and held at 20 to 60°C for 2 hours or more. In this case, the concentration of the cyclodextrin compound in the aqueous solution is not particularly limited, but within the range of solubility, it is preferably about 10 to 50 mM. The temperature is 20℃
If the temperature is lower, it will take a longer time to form the complex, and if it exceeds 60°C, there is a risk of decomposition of the cyclodextrin, so a range of 20 to 60°C is appropriate.

The resulting composite was separated from the liquid and washed with water for 30 to 40 minutes.
Drying for 12-24 hours at °C yields a crystalline montmorillonite-methylated cyclodextrin complex.

This composite has a microcomposite structure in which a methylated cyclodextrin layer is incorporated between the silicate layers of montmorillonite, and the interlayer distance is 12
It increases from ~15 Å (varies depending on the type of substituent ion and degree of dehydration) to the thickness of one molecular layer of methylated cyclodextrin (8-15 Å).

In addition, in the case of a ternary complex containing a third component in addition to montmorillonite and methylated cyclodextrin, this third component is added in place of an aqueous solution of methylated cyclodextrin in the synthesis of a binary complex.
It can be easily obtained by using a mixed solution containing both at a concentration of ~100mM.

In the crystalline composite of the present invention, a methylated cyclodextrin having a cylindrical cavity is present alone or together with other organic components between layers of montmorillonite to form a crystalline composite.

Effects of the Invention Since the complex of the present invention has the above-mentioned structure, (1) Even when a single cyclodextrin compound is used, the drug elutes and decomposes relatively quickly and has poor drug efficacy. By forming the composite of the present invention, the drug is fixed and retained in the cyclodextrin intramolecular cavity between the montmorillonite layers, so the elution and decomposition of the drug are suppressed, resulting in long-term drug efficacy and long-lasting drug and drug properties. It is excellent as a microcapsule agent for agricultural chemicals, organometallic catalysts, etc.

(2) In the composite of the present invention, the separation effect of the montmorillonite layer is synergized, so the separation ability is improved.
It can also exhibit effects such as being an excellent chromatography filler.

Example 1 Na-montmorillonite, Na _0.34 K _0.008 Ca _0.03
(Al _1.60 Fe _0.10 Mg _0.32 ) (Si _3.83 Al _0.17 ) O ₁₀ (OH) ₂・
0.1 g of 6H ₂ O and 8 ml of a 12.5 mM aqueous solution of hexakis-2,6-di-O-methyl-α-cyclodextrin were mixed and shaken at 25° C. for 10 days. After centrifuging the solid phase, it was washed with water and dried at 40°C to obtain a complex.

The X-ray diffraction pattern of this composite is shown in Figure 1a, and the interlayer distance has increased from 12.6 Å before reaction to 21.4 Å. The thickness of the included cyclodextrin layer, 11.9 Å, indicates that the cyclodextrin molecules are aligned in a monolayer with the central cavity axis perpendicular to the silicate layer.

Example 2 Ca-montmorillonite, Ca _0.278 (Al _1.60 Fe _0.10
Mg _0.32 ) (Si _3.83 Al _0.17 ) O ₁₀ (OH) ₂・10H ₂ O 0.1g
and 8 ml of a 25 mM aqueous solution of heptakis-2,6-di-O-methyl-β-cyclodextrin (hereinafter abbreviated as DM-β-CD) were mixed and shaken at 25°C for 10 days.

X of the complex obtained by centrifugation, washing with water, and drying
The line diffraction pattern is shown in Figure 1b. The interlayer distance increases from 14.9 Å before reaction to 17.9 Å.

Example 3 Cu-montmorillonite, Cu _0.237 (Al _1.60 Fe _0.10
Mg _0.32 ) (Si _3.83 Al _0.17 ) O ₁₀ (OH) _{2.5H 2} O 0.1 g and heptakis-2,3,6-tri-o-methyl-β
- Mixed with 8 ml of a 25 mM aqueous solution of cyclodextrin and shaken at 25°C for 10 days.

The X-ray diffraction pattern of the obtained composite after drying at 40°C is shown in Figure 1c. The interlayer distance is from 12.4 Å before reaction.
It increased by 7.9 Å to 17.4 Å.

Example 4 0.1g of the above Na-montmorillonite was added to 50mM
Suspend in 8 ml of a 1:1 mixed solution of DM-β-CD solution and 1M sodium benzenesulfonate solution,
Shake for 5 days at °C. The product was added to 50mM DM-β
- After washing with CD solution, it was dried at 40°C.

The interlayer distance of the obtained composite was 23.3 Å.
The thickness of the inclusion layer (13.8 Å) of this ternary complex is Na
-It is increased by 6.2 Å compared to the inclusion layer of the montmorillonite-DM-β-CD binary complex, indicating that benzenesulfonate ions and cyclodextrin molecules are double included between the montmorillonite layers. There is.

[Brief explanation of the drawing]

FIG. 1 is an X-ray diffraction pattern of the crystalline composite of the present invention, and a, b, and c show the measurement results for the composites obtained in Examples 1, 2, and 3, respectively.

Claims (1)

[Claims] 1 General formula (X, Y) _2~3 Z ₄ O ₁₀ (OH) ₂ ·mH ₂ O(W) _n (where X is Al, Fe(), Mn(), and Cr
Trivalent metal selected from (), Y is Mg, Fe (),
Divalent metal selected from Mn () and Ni, Z is Si,
Or montmorillonite with a layered structure represented by Al, W is a metal selected from Cu (), K, Na, and Ca, m is the number of water molecules), and methylated cyclodextrin is interposed between the layers, either alone or with other materials. A montmorillonite-methylated cyclodextrin-based crystalline complex consisting of montmorillonite and methylated cyclodextrin present together with organic molecules. 2 General formula (X, Y) _2~3 Z ₄ O ₁₀ (OH) ₂・mH ₂ O(W) _n (X is Al, Fe (), Mn () and Cr
Trivalent metal selected from (), Y is Mg, Fe (),
Divalent metal selected from Mn () and Ni, Z is Si,
Alternatively, montmorillonite powder having a layered structure represented by Al, W is a metal selected from Cu (), K, Na, and Ca, and m represents the number of water molecules) is mixed with methylated cyclodextrin alone or with other organic molecules. 1. A method for producing a montmorillonite-methylated cyclodextrin-based crystalline composite, which comprises moistening the composite with an aqueous solution containing the following.