JP2002327338A - Fiber for removal of toxic substance comprising polymer clathrate compound, method for producing the same, and use of the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a polymer clathrate compound in a practical form and a method for producing the polymer. SOLUTION: This fiber is composed of a polymer clathrate compound in which cyclic oligosaccharides are bound to straight-chain aminopolysaccharides. The cyclic oligosaccharides is binded to the straight-chain aminopolysaccharides by reductive condensation.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a fiber containing a polymer inclusion compound and an organic compound capable of forming a polymer inclusion complex. The present invention also relates to a method for producing the fiber and its use in removing harmful substances such as environmental hormones.

[0002]

2. Description of the Related Art Cycloglycan (CG) such as cyclodextrin (CD) is a cyclic oligosaccharide having an inclusion function, and is widely used in the fields of food, sanitary materials, medical-physiological materials and the like. For example, cyclodextrin has been widely used as an inclusion complex or as an additive, in the field of oral administration preparations such as converting unstable drugs such as prostaglandins into stable preparations. In recent years, in particular, the nutritional food industry
al industry) (Frank, SGJ Pharm. Sci. 1975, 64, 1585).

[0003] Cyclic oligosaccharides have a hydrophobic cavity consisting of a plurality of monosaccharide units. In addition, it has an inclusion function of incorporating various organic compounds into the cavity to form a complex by hydrophobic interaction. Due to these extremely unique properties, cyclic oligosaccharides have become an independent subject of study in host-guest chemistry (Szejtli, J. et al.
Cyclodextrin and Their Inclusion Complexs; Akademi
ai Kaido: Budapest, 1982; Li, S .; Purdy, WC Che
m. Rev. 1992, 92, 1457.). Further, in order to impart a new function to cyclodextrin, many attempts have been made to carry out chemical transformation such as introduction of a substituent into the cyclodextrin. For example, Tetrahedron, 39, 1417 (1983) describes a technique for performing chemical conversion such as acylation, alkylation, amination, acidification, and halogenation, and a converted derivative. Numerous studies in the field of artificial enzymes have also been performed using cyclic oligosaccharides and their derivatives (Bleslow, R. Science 1982, 218, 532; D'Soud).
a, VT; Bender, MLAcc. Chem. Res. 1987, 20, 1
46).

Furthermore, macromolecules containing cyclic oligosaccharides as constituents utilizing the above-mentioned inclusion function have been widely used in the field of analytical chemistry (Journal of Ana).
lytical Chemistry, 211, 333 (1988)). As an example, HPLC for the isolation of various stereoisomers and enantiomers
(Armstrong, DW; DeMond, W .; Alak, A; Hinze, W.
L .; Riehl, TE; Bui, KH, J. Analytical Chemistr
y, 1985, 57, 234, and Armstrong, DWJ Pharm. Bi
Anal. 1990, 8, 123) and affinity chromatography to separate biopolymers such as fibroblast growth factor (Sheng, Y .; Forkman, J .; Weisz, PB; Joul
lie, MM; Ewing, WR Anal. Biochem. 1990, 185,
108).

Based on these findings, the present inventor has proposed a novel polymer clathrate which has biocompatibility and can be used as a medical-physiological material, cosmetic additive, food additive, sanitary material and the like. As a sex compound, a derivative of cycloglycan and chitosan was invented (Japanese Patent No. 3103532). He has also shown that a particularly useful use of the novel polymeric inclusion compound is in the removal of harmful organic compounds such as environmental hormones (endocrine disruptors).

By the way, environmental hormones refer to the processes of synthesis, storage, secretion, transport in the body, receptor binding, hormonal action, degradation and excretion of various in vivo hormones related to homeostasis, reproduction, development and behavior. It is an exogenous substance that inhibits, and for example, bisphenol A, p-nitrophenol, phthalic acids, dioxins, polychlorinated biphenyls, tin compounds and the like are known. Traces of endocrine disrupters that have flowed into the natural world accumulate in higher organisms in the food chain and are even feared to deprive them of reproductive function. This environmental pollution has become a major social problem, but no effective solution has yet been found. Therefore, development of a method for efficiently removing environmental hormones from the environment is desired.

The above-mentioned novel polymer inclusion compound has an effect of removing environmental hormones by its inclusion function, but it is difficult to put it to practical use in its own form. On the other hand, it was also impossible to modify the form and actually use it.

[0008]

Accordingly, an object of the present invention is to provide the above-mentioned polymer inclusion compound in a practical form and to a process for producing the same.

[0009]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies to solve the above-mentioned problems, and as a result, succeeded in forming the polymer clathrate into fibers to complete the present invention. . According to the present invention, the polymer inclusion compound that can be used as a harmful substance removing means can be provided in the form of a fiber. And, by making the obtained fiber into a product such as a filter, it becomes possible to use it for removing harmful substances.

That is, the present invention relates to a fiber comprising a high molecular weight inclusion compound in which a cyclic oligosaccharide is bonded to a linear amino polysaccharide. Further, the present invention relates to the fiber, wherein the linear amino polysaccharide is a linear polymer residue composed of an amino group-containing monosaccharide. Furthermore, the present invention relates to the fiber, wherein the linear amino polysaccharide is a chitosan residue. Also, the present invention
The present invention relates to the fiber, wherein the linear amino polysaccharide and the cyclic oligosaccharide are bonded by a divalent alkylidene group. Furthermore, the present invention relates to the fiber, wherein the cyclic oligosaccharide is a cycloglycan branched to a linear amino polysaccharide via a crosslinking group. Further, the present invention provides a method wherein the cycloglycan is α-, β-
Or, it is a γ-cyclodextrin residue. Further, the present invention provides a compound represented by the following formula (I):

Embedded image (Wherein, CG is a cycloglycan residue formed of 6 to 8 monosaccharides, R ₁ is a hydrogen atom or a derivative group of a hydroxyl group and does not interfere with the inclusion of cycloglycan,
R ₂ is a hydrogen atom or an acyl group having 1 to 20 carbon atoms, and R ₃ is a crosslinkable group). The present invention also relates to the fiber, wherein the CG is an α-, β- or γ-cyclodextrin residue.
Furthermore, the present invention relates to the fiber, wherein the molecular weight is at least 20,000. The present invention also relates to a method for producing a fiber comprising a polymer inclusion compound, comprising forming a linear amino polysaccharide into a fibrous form into a linear amino polysaccharide fiber, The present invention relates to the above method, wherein the cyclic oligosaccharide is bound by condensation. Furthermore, the present invention relates to the above method, which comprises a crosslinking reaction between linear amino polysaccharides. The present invention also relates to the above method, wherein the crosslinking reaction is performed using hexamethylene diisocyanate. Furthermore, the present invention relates to the above method, wherein the reductive condensation is performed using a cyclic oligosaccharide modified with an aldehyde group. The present invention also relates to the above method, wherein the reductive condensation is performed using a cyclic oligosaccharide in which a hydroxyl group has been converted to a methyl ether type or an allyl ether type. Furthermore, the present invention relates to the above method, wherein cycloglycan is used as the cyclic oligosaccharide.
The present invention also relates to the above method, wherein α-, β- or γ-cyclodextrin is used as the cyclic oligosaccharide. Further, the present invention relates to a fiber produced by any one of the above methods, comprising a polymer clathrate. The present invention also relates to the use of the fiber in removing harmful substances. Furthermore, the present invention relates to the above use, wherein the harmful substance is an environmental hormone.

According to the present invention, since the polymer inclusion compound can be formed into a fiber shape, application to practical use is realized. For example, if the fiber is used as a filter or a column filler, harmful substances such as bisphenol A and p-nitrophenol and other environmental hormones are removed from water and food through a guest-host complex contained in the fiber. be able to. That is, the present invention is widely applied to technical fields such as the environmental protection industry field.

[0012]

DETAILED DESCRIPTION OF THE INVENTION The production of fibers according to the present invention comprises the step of attaching cyclic oligosaccharides to linear amino polysaccharide fibers by reductive condensation with the fibers. The fiber of the present invention preferably has a molecular weight of 20,000 or more.
This is because if the molecular weight is low, the solubility of the fiber becomes high, and it becomes difficult to produce the fiber.

In the present invention, the molding of the linear amino polysaccharide fiber is carried out by a method known per se. For example, according to the production method using various alkaline solutions as a coagulant described in the Journal of the Textile Society of Japan (1987), vol. 43, page 56, chitosan fibers used in the production method according to the present invention are produced. As the alkaline solution in the production method of the present invention, a potassium hydroxide solution, a sodium hydroxide aqueous solution, a copper ammonia solution, and a solution thereof diluted with various alcohols are preferably used.

In the step of binding the cyclic oligosaccharide to the linear aminopolysaccharide fiber, the cyclic oligosaccharide dissolves during its introduction, and the binding of the linear aminopolysaccharide fiber component can be performed. May not be. This is avoided by pre-crosslinking the linear aminopolysaccharides with one another. The crosslinking is suitably performed by using a crosslinking agent such as a disubstituted isocyanate such as hexamethylene diisothiocyanate or a dialdehyde such as glutaraldehyde.

The reductive condensation of both components in the step of bonding the linear amino polysaccharide fiber and the cyclic oligosaccharide is performed at the amino group of the linear amino polysaccharide fiber. The reductive binding is performed by adding the previously oxidized cyclic oligosaccharide to the linear amino polysaccharide fiber and stirring the mixture in the presence of a reducing agent. Oxidants such as ozone, osmium oxide and chromates are used for the oxidation of cyclic oligosaccharides, and reducing agents such as borane derivatives such as sodium cyanoborohydride, sodium borohydride and borane dimethylamine complex are used for reductive condensation. It is preferably used.

As the cyclic oligosaccharide to be bonded to the linear amino polysaccharide fiber, a partially modified cyclic oligosaccharide is more preferably used to bond the two components. As the modifying group in this case, those having an aldehyde group, a ketone group and the like are suitable. Further, the use of a derivative in which the hydroxyl group of the cyclic oligosaccharide is converted into a methyl ether type, an allyl ether type, a butyl or hydroxypropyl ether type, etc. is there.

In the present invention, the cyclic oligosaccharide is a cycloglycan branched to a linear amino polysaccharide via a cross-linking group. Examples of the cycloglycan include cycloisomaltooligosaccharides and cycloinulooligosaccharides. And the like. Typically, α-, β- or γ-cyclodextrin (CD) is used. The amino polysaccharide skeleton can be any amino polysaccharide residue including those having biocompatibility and biodegradability, for example, a linear chain composed of amino group-containing monosaccharides such as polygalactosamine and chondroitin sulfate. Polymer residue, typically a chitosan residue.

Further, the group linking the linear amino polysaccharide and the cyclic oligosaccharide is typically a divalent alkylidene group bridging the amino polysaccharide and cycloglycan.
Since most of the above substances are inexpensive and easily available natural products, the use of the fibers of the present invention makes it possible to construct products for removing harmful substances such as environmental hormones at extremely low cost.

Mizu-Q as a straw water purifier
(Product name: Akihiro Corporation) is sold as an overseas travel product. This product purifies by putting activated carbon into a cylindrical plastic container made of polypropylene as a raw material. However, activated carbon is not suitable for adsorbing almost all organic compounds and selectively removing only specific substances. On the other hand, by using a product in which the chitosan fiber of the present invention is wound around a straw instead of activated carbon, it is possible to manufacture a product having a filter function capable of selectively removing environmental hormones and the like. Also, if you scale this up,
Application to large-scale processing systems is also possible.

The aminopolysaccharide fiber used for producing the fiber containing the polymer inclusion compound of the present invention is obtained by stirring an aminopolysaccharide in an acid such as acetic acid diluted with distilled water. It is manufactured by passing this through a coagulating liquid and a washing liquid. This series of steps can be performed extremely easily and efficiently by using a stringing device including a stretching device and a winding roller as components.

[0021]

The present invention will be described below with reference to examples, but the scope of the present invention is not limited to these examples.

Example 1 Production of CD-Binding Chitosan Fiber CD-binding chitosan fiber was produced by the following steps a) to d). a) Preparation of chitosan fiber Dilute acetic acid (10 ml) with distilled water to 500 ml,
Chitosan (40.0 g) was added and stirred with a mechanical stirrer for about 3 days to prepare a viscous yellow solution. This was filtered with a cotton cloth and left in a refrigerator for one day to degas to prepare a chitosan dope. Ice from deionized water (500
Potassium hydroxide (500 g) was dissolved in ethylene glycol (2500 ml) to which g) was added to prepare a coagulation liquid. Deionized water (1000 ml) and methanol (200
0 ml) to obtain a washing solution. This chitosan dope was pressed under pressure to have a diameter of 15 mm, a number of pores of 50, and a pore diameter of 0.09 m.
The resin was extruded from a nozzle m into a coagulation bath, passed through a washing bath, and wound around a bobbin by a winding roller. The obtained chitosan fiber was sufficiently washed with a water-methanol (1: 1) mixed solvent to remove alkali, and then removed from the bobbin and stored in water.

B) Cross-linking of chitosan fiber Chitosan fiber (3) which was lightly sandwiched with filter paper to remove water
3.5 g) was placed in methanol, hexamethylene diisocyanate (0.3 ml) was added, and the mixture was stirred overnight. The obtained fiber was insoluble in acetate buffer (pH = 4), and it was confirmed that the cross-link formation was complete.

C) Allylation and methylation of β-CD β-CD was dissolved in distilled dimethyl sulfoxide (200 ml).
Add CD (23.42 g) with stirring to dissolve and steam.
Distilled tetrahydrofuran (200 ml) was added. this
Sodium hydride (8 g) was added little by little to water ice
And tetrahydrofuran (20 ml) with bromide
Allyl (5.5 ml) was added via dropping funnel. 3 hours later
Since the progress of the reaction was stopped, allyl bromide (5.5 m
l) was further added and stirred overnight. Further hydrogenated sodium
(8 g) and tetrahydrofuran (100 m
l) and dimethyl sulfate (29.8 ml) using a dropping funnel
And added. Since the reaction did not proceed, while cooling
Sodium hydride (12g) and imidazole (1g)
The mixture was stirred overnight. Methanol, water, ammonia water
The reaction was stopped, and the mixture was concentrated under reduced pressure. Sodium thiosulfate
And then decolorized, adjusted to pH = 5-6 with 2N hydrochloric acid
And extracted with chloroform. Dry with magnesium sulfate
After concentration under reduced pressure, column chromatography (silica gel)
Kagel, CHCl ₃; CHCl₃-CH₃OH (1: 1
99); CHCl₃-CH₃OH (1:99); CHC
l₃-CH₃OH (3: 177); CHCl₃-CH₃
OH (3: 147)) (yield; 21.048)
g).

D) Preparation of CD-Bound Chitosan Fiber The β-CD derivative (2.68 g) prepared in c) was dissolved in methanol (20 ml), and ozone was bubbled for 1.5 hours and then oxygen for 1 hour. By this treatment, the reaction solution changed from yellow to colorless. Add dimethyl sulfide (3m
l) was added and the mixture was stirred at room temperature overnight. After adding water (20 ml), methanol and dimethyl sulfide were distilled off under reduced pressure. 150 ml of 0.2 M buffer (pH = 4)
The chitosan fiber crosslinked in b) was immersed therein, and the ozone-oxidized β-CD derivative was added thereto and stirred for 2 hours. Further, sodium cyanoborohydride (0.291 g) was added, and the mixture was stirred at room temperature overnight.

Example 2 Inclusion Test Using p-Nitrophenol A CD-bound chitosan fiber prepared in d) was applied to a column (diameter 1).
cm, height 10 cm) and the chitosan fiber was washed with water (about 500 ml). Then 5.36 × 10 ^-5 mo
1 / l p-nitrophenol phosphate buffer solution (3
gently) and left for about 10 minutes, then add water (100m
1) was flowed down to wash the column. At this stage, unencapsulated p-nitrophenol is eluted. Thereafter, ethanol (30 ml) was flowed down, and UV measurement was performed. As a result, when the column was washed with water (80 ml),
In all the fractions, UV absorption was 0.01 or less and p-nitrophenol was not eluted (FIG. 1). Next, when the measurement was performed by flowing down ethanol, strong UV absorption was observed in the fractions. This indicates that the CD-bound chitosan fibers include p-nitrophenol in water and elute in 20 ml (about 3 times the adsorbent volume) of alcohol (FIG. 1).

Example 3 Inclusion test using bisphenol A CD-bonded chitosan fiber prepared in d) was applied to a column (diameter 1).
cm, height 10 cm) and the chitosan fiber was washed with water (about 500 ml). Then bisphenol A
3 ml of (9.64 × 10 ⁻⁵ mol / l) was gently poured, allowed to stand for about 10 minutes, and water (100 ml) was allowed to flow down to wash the column. At this stage, unencapsulated bisphenol A is eluted. Thereafter, ethanol (50 ml) was allowed to flow down to elute the included bisphenol A, and only ethanol was dried under reduced pressure. Thereafter, fluorescence measurement was performed. As a result, with respect to bisphenol A, when the column was washed with 100 ml of water, the CD-bound chitosan fiber had fluorescence of 60 or less and did not elute bisphenol A in any of the fractions. On the other hand, when the measurement was performed by flowing down ethanol, bisphenol A was eluted with 30 ml of alcohol (FIG. 2). From the above results, it is apparent that the fiber containing the polymer inclusion compound according to the present invention has the ability to remove environmental hormones such as p-nitrophenol and bisphenol A by the action of including these substances. became.

The samples used were as follows. A: CD-bound chitosan fiber B: CD-bound chitosan fiber covered with PNP C: CD-bound chitosan fiber covered with PNP and washed with ethanol D: Chitosan fiber [Manufactured in Experimental Operation a] The fiber drawing was performed using the machine shown in FIG.

[0029]

Industrial Applicability The fiber containing the polymer inclusion compound provided by the present invention has an ability to remove harmful substances such as environmental hormones since it has an inclusion effect by cycloglycan. Therefore, harmful substances such as environmental hormones can be removed using the fibers.

[0030]

[Brief description of the drawings]

FIG. 1 is a graph showing the effect of chitosan fibers on the inclusion of p-nitrophenol.

FIG. 2 is a graph showing the effect of inclusion of bisphenol A by chitosan fiber.

FIG. 3 is a diagram schematically illustrating an example of a chitosan fiber spinning device.

Claims (19)

[Claims] 1. A fiber comprising a polymer inclusion compound in which a cyclic oligosaccharide is bonded to a linear amino polysaccharide. 2. The fiber according to claim 1, wherein the linear amino polysaccharide is a linear polymer residue composed of an amino group-containing monosaccharide. 3. The fiber according to claim 1, wherein the linear amino polysaccharide is a chitosan residue. 4. The fiber according to claim 1, wherein the linear amino polysaccharide and the cyclic oligosaccharide are linked by a divalent alkylidene group. 5. The fiber according to claim 1, wherein the cyclic oligosaccharide is a cycloglycan branched to a linear amino polysaccharide via a bonding group. 6. The method according to claim 6, wherein the cycloglycan is α-, β- or γ.
Fiber according to claim 5, characterized in that it is a cyclodextrin. 7. A compound represented by the following formula (I):(Wherein, CG is cyclog formed from 6 to 8 monosaccharides.
Lican residue, R₁Is a hydrogen atom or a hydroxyl derivative group
And does not interfere with the inclusion of cycloglycan,
₂Represents a hydrogen atom or an atom having 1 to 20 carbon atoms.
A sil group, ₃Is a crosslinkable group).
7. The method according to claim 1, which comprises a molecular inclusion compound.
The fiber according to claim 1. 8. The fiber according to claim 7, wherein the CG is an α-, β- or γ-cyclodextrin residue. 9. The fiber according to claim 1, which has a molecular weight of at least 20,000. 10. A method for producing a fiber comprising a polymer inclusion compound, comprising forming a linear amino polysaccharide into a fiber to obtain a linear amino polysaccharide fiber, The above method, wherein the cyclic oligosaccharide is bound by condensation. 11. The method according to claim 10, comprising a cross-linking reaction between linear aminopolysaccharides. 12. The method according to claim 11, wherein the crosslinking reaction is carried out using hexamethylene diisocyanate. 13. The method according to claim 11, wherein the reductive condensation is carried out using a cyclic oligosaccharide modified with an aldehyde group. 14. The method according to claim 10, wherein the reductive condensation is carried out using a cyclic oligosaccharide having a hydroxyl group converted to a methyl ether type or an allyl ether type. 15. The method according to claim 10, wherein cycloglycan is used as the cyclic oligosaccharide. 16. The method according to claim 10, wherein α-, β- or γ-cyclodextrin is used as the cyclic oligosaccharide. 17. A fiber comprising a polymer inclusion compound, produced by the method according to claim 10. Description: 18. Use of the fiber according to any one of claims 1 to 9 and 17 for removing harmful substances. 19. The use according to claim 18, wherein the harmful substance is an environmental hormone.