JP3094080B2 - Sugar-containing polymer - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a sugar-containing polymer.

[0002]

2. Description of the Related Art Hitherto, sugar-containing polymers have been:
It has been reported that sugar-based polymers can be obtained by polymerizing sucrose acrylate monomers [Macromolecules, vol. 24, p3
462-3463 (1991)]. In such a saccharide-containing polymer, the spacer portion (—OCO—) between the saccharide and the main chain is short, so that it is difficult to sufficiently exhibit the intrinsic function of the saccharide. On the other hand, it has been reported that reducing sugars have an active oxygen generating action, and that the virus is inactivated by active oxygen generated from the reducing sugars [protein nucleic acid enzyme, 33, 3116-3126].
(1988)]. Further, as a sugar-containing polymer having a branch (side chain) of a reducing sugar that generates active oxygen, a synthetic polymer in which a 3-position of glucose is bonded to a polystyrene main chain via a spacer has been reported. It has been reported that the molecular form of the monomer increases its active oxygen generating action as compared to the original monomer [Organic Synthetic Chemistry 4
2, 523-535 (1984)]. However, since such a sugar-containing polymer is chemically synthesized using 1,2, -4,6-diisopropylideneglucose as a raw material, only a glucose derivative having a 3-position substitution and a glucose derivative can be synthesized. . Therefore, a polymer having a branch of a reducing sugar other than glucose has not been obtained. Also,
Since the main chain is also polystyrene, it has no biodegradability. It is known that glucose has a low ability to generate active oxygen among reducing sugars. Therefore, it is expected that by synthesizing a high-molecular-weight polymer having a sugar branch having a higher active oxygen generating ability than glucose, the active oxygen generating ability can be more sufficiently exhibited.

[0003]

An object of the present invention is to provide a sugar-containing polymer having a structure in which a sugar residue is bonded to polyvinyl alcohol via at least three carbon chains.

[0004]

Means for Solving the Problems The present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, have completed the present invention. That is, according to the present invention, the following general formula (1)

Embedded image S (OH) q ₋₁ —OOC—R—COOCH ＝ CH ₂ (1) (wherein, S (OH) q ₋₁ is a sugar skeleton S and q bonded thereto
A monovalent saccharide residue obtained by removing one hydroxyl group from a saccharide compound comprising two hydroxyl groups, R represents an alkylene group, and q represents 4
Or 5) is represented by the following formula:
The following general formula (2)

Embedded image (Wherein, S (OH) q _-2 represents a sugar skeleton S and q
A divalent saccharide residue obtained by removing two hydroxyl groups from a saccharide compound comprising two hydroxyl groups, R represents an alkylene group, and q represents 4
Or the number of 5) is obtained by a copolymerization reaction with the polymerizable sugar ester B represented by the formula (1), wherein the ratio of the polymerizable sugar ester B contained in the polymer molecule is There is provided a sugar-containing polymer characterized by a ratio of 0.05 to 10 mol per 100 mol of ester A.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION The saccharide compounds used in the present invention include natural monosaccharides and synthetic saccharides. These sugar compounds can be represented by the following general formula ( 3 ).

In the formula, S (OH) q ( 3 ) (wherein S represents a sugar skeleton, q represents the number of hydroxyl groups bonded thereto and represents the number of 4 or 5). Glucose, mannose, galactose and the like can be mentioned.

According to the present invention, there is provided a sugar-containing polymer comprising a copolymer of the polymerizable sugar ester A represented by the general formula (1) and the polymerizable sugar ester B represented by the general formula (2). Causes the polymerizable sugar esters A and B to undergo a polymerization reaction in the presence of a polymerization initiator.

As the polymerization initiator, besides organic peroxides and azo compounds, redox polymerization initiators, especially Fenton's reagent, can be used. In the case of the present invention, hydrogen peroxide alone can be used as the polymerization initiator. As the organic peroxide and the azo compound, those commonly used in polymerization of vinyl compounds, for example, benzoyl peroxide, 2,2'-azoisobutyronitrile and the like are used. Its usage is
It is 0.01 to 2 equivalents, preferably 0.1 to 1 equivalent, per equivalent of the polymerizable sugar ester. When a polymerization reaction is carried out using an organic peroxide or an azo compound as a polymerization initiator, the reaction temperature is 0 to 200 ° C, preferably 30 to 60 ° C.
It is. The polymerization reaction can be carried out in the presence of a reaction solvent. As the reaction solvent, for example, a polar organic solvent such as dimethylformamide, dimethylsulfoxide, dioxane and the like is used. When a reaction solvent is used, the concentration of the polymerizable sugar ester in the reaction solvent is 1 to 90% by weight, preferably 20 to 50% by weight.

[0008] The redox polymerization initiator comprises a combination of a peroxide and a reducing agent. As peroxides,
Examples include hydrogen peroxide, benzoyl peroxide, cumene hydroperoxide and the like. Examples of the reducing agent include ferrous salts (such as iron chloride and iron sulfate), chromium ions, sulfites, hydroxylamine, and hydrazine. In the redox polymerization initiator, the peroxide is used in an amount of 0.0001 to 001% by weight, preferably 0.0005 to 0.005% by weight, based on the polymerizable sugar ester. Is 0.01 to 1% by weight, preferably 0.05 to 0.5% by weight, based on the polymerizable sugar ester. When a polymerization reaction is carried out using a redox-based polymerization initiator, the reaction temperature is 0 to 100 ° C, preferably 10 to 40 ° C. In this case, the polymerization reaction can be carried out in the presence of a reaction solvent. Examples of the reaction solvent include water, dimethylformamide, dimethylsulfoxide, and a water-containing organic solvent. The concentration of the polymerizable sugar ester in the reaction solvent is 1 to 90% by weight, preferably 10 to 40% by weight. In the present invention, a Fenton reagent or hydrogen peroxide can be preferably used as a polymerization initiator.
When such a polymerization initiator is used, a high molecular weight sugar-containing polymer having a number average molecular weight of 20,000 or more can be obtained without using a special linking agent.

The polymer obtained as described above has a substantially linear structure, and has a number average molecular weight of 1,000 or more,
Usually 2000 or more, the upper limit of which is 1,000,000 to 200
It is about ten thousand. This sugar-containing polymer is rich in hydrophilicity and has excellent biodegradability. When polymerizing the polymerizable sugar ester, another co-reactant may be added in an appropriate amount and copolymerized, if necessary. Examples of such a co-reactant include methyl acrylate, methyl methacrylate, acrylamide, methacrylamide, vinyl acetate, 2-methylene-1,3,6-trioxocan, and the like.

In the present invention, the reaction rate of the polymerizable sugar ester B represented by the general formula (2) may be an amount which does not impair the linear structure of the obtained polymer. The ratio is 0.05 to 10 mol, preferably 0.1 to 4 mol, per 100 mol of the polymerizable sugar ester A of the general formula (1) contained in the resulting polymer. When the ratio of the polymerizable sugar ester B of the general formula (2) exceeds the above range, the obtained polymer shows a hard gel state. The polymer thus obtained has a linked structure represented by the following general formula ( 4 ), has a high molecular weight, and has an increased melting temperature and mechanical strength.

Embedded image [In the above formula, Z ¹ is the following general formula ( 5 ))

Embedded image -OOC-R-COO-S (OH) q-1 ( 5 ) (wherein, S (OH) q- ₁ is a sugar skeleton S and q bonded thereto.
A monovalent saccharide residue obtained by removing one hydroxyl group from a saccharide compound comprising two hydroxyl groups, R represents an alkylene group, and q represents 4
Or a number of 5), and Z ² is a group represented by the following general formula ( 6 )

Embedded image (Wherein, S (OH) q _-2 represents a sugar skeleton S and q
A divalent saccharide residue obtained by removing two hydroxyl groups from a saccharide compound comprising two hydroxyl groups, R represents an alkylene group, and q represents 4
Or a number 5))

The polymerizable sugar ester represented by the general formulas (1) and (2) is represented by the following general formula ( 3 )

And a sugar compound represented by S (OH) q ( 3 ) (wherein S represents a sugar skeleton, q represents the number of hydroxyl groups bonded thereto and represents the number of 4 or 5), and General formula ( 7 )

Embedded image Reaction of an aliphatic dicarboxylic acid divinyl ester represented by CH ₂ ＣＨCHOOC—R—COOCH ＝ CH ₂ ( 7 ) (wherein R represents an alkylene group) in the presence of a hydrolase Can be manufactured by In the general formula (7), the alkylene group R is an alkylene group having 1 or more carbon atoms, preferably 2 carbon atoms.
To 8 alkylene groups. Aliphatic dicarboxylic acid divinyl esters are derived from aliphatic dicarboxylic acids such as malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, nonanedicarboxylic acid, dodecanedicarboxylic acid and the like. Things can be mentioned. Examples of the hydrolase used in the reaction include conventionally known ones, for example, various proteases such as Streptomyces-derived protease and Bacillus-derived protease. The enzyme is preferably used in a powder form, and the liquid enzyme is preferably used after being lyophilized into a powder form.

In order to preferably produce the above polymerizable sugar ester, a sugar compound and an aliphatic dicarboxylic acid divinyl ester are reacted in a reaction solvent in the presence of an enzyme. The reaction in this case is represented by the following equation.

Embedded image The reaction is carried out at a temperature of 30-70 ° C, preferably 30-50 ° C.
Performed at ° C. Any reaction solvent may be used as long as it shows compatibility with the reaction raw materials and is liquid under the reaction conditions. Examples of such a solvent include organic solvents such as dimethylformamide, pyridine, and dimethylsulfoxide. The concentration of the saccharide compound in the reaction solvent is 1 to 20% by weight, preferably 2 to 1%.
0% by weight. The proportion of the aliphatic dicarboxylic acid divinyl ester used is 1 to 20 equivalents, preferably 2 to 10 equivalents, per equivalent of the sugar compound. The use ratio of the hydrolase is 0.1 to 20% by weight, preferably 0.1 to 1% by weight, based on the reaction solvent. The position of the hydroxyl group of the sugar compound at which the divinyl ester of the aliphatic dicarboxylic acid reacts with the sugar compound is usually a hydroxyl group bonded to carbon 6 of the hexopyranose nucleus or a hydroxyl group bonded to carbon 1 of the hexofuranose nucleus. .

The polymer according to the present invention containing a reducing sugar having a linking structure represented by the following general formula ( 9 ) in its molecule acts as an active hydrogen generator.

Embedded image [In the above formula, X ¹ represents the following general formula ( 10 )

Embedded image -OOC-R-COO-Q (OH) q _-1 ( 10 ) (wherein Q (OH) q _-1 is a reducing sugar compound comprising a reducing sugar skeleton Q and q hydroxyl groups bonded thereto. Represents a monovalent reducing sugar residue obtained by removing one hydroxyl group from R, R represents an alkylene group, and q represents a number of 4 or 5);
X ² is represented by the following general formula ( 11 )

Embedded image (Wherein Q (OH) q _-2 represents a divalent reducing sugar residue obtained by removing two hydroxyl groups from a reducing sugar compound comprising a reducing sugar skeleton Q and q hydroxyl groups bonded thereto, and R represents an alkylene Represents a group, and q represents a number of 4 or 5, and q represents a number of 4 or 5.) In the case of producing a polymer containing the reducing sugar, the polymerization initiator may be A redox polymerization initiator, in particular, a Fenton's reagent consisting of a ferrous salt and hydrogen peroxide can be used, and preferably only hydrogen peroxide can be used. Examples of the reducing sugar in the reducing sugar-containing polymer include various monosaccharides such as glucose, mannose, and galactose. The polymer having a branch (side chain) of the reducing sugar is a highly safe polymer having a biodegradability and an active oxygen generating function, and its active oxygen generating function is much larger than the active oxygen generating function of the reducing sugar itself. It is an improvement. In this polymer, the bond between the sugar and the polymer is an ester bond,
After the decomposition, the sugar is released immediately, and the ability to generate active oxygen decreases. Further, since the main chain is polyvinyl alcohol having biodegradability, the polymer is advantageously applied as a biodegradable active oxygen generator in a field where a bactericidal action and a deodorant action are expected. You.

[0014]

Next, the present invention will be described in more detail with reference to examples.

REFERENCE EXAMPLE 1 4.28 g of maltose [C ₁₂ H ₁₄ O ₃ (OH) ₈ ] and 19.82 g of divinyl adipate were sufficiently dried with a molecular sieve (3A) to obtain dimethylformamide (D).
MF) and dissolved in 50 ml of Streptomyces (Str)
eptomyces) -derived alkaline protease (manufactured by Toyobo) (250 mg) was added and suspended. This enzyme reaction liquid was stirred at 130 rpm at 35 ° C. for 7 days. The concentration of maltose in this enzyme reaction solution was measured using an amide column (TSKgel Amide-80, manufactured by Tosoh Corporation) with a mobile phase of acetonitonitrile / water (75:25) at a flow rate of 1.
The solution was flowed at 0 ml / min and detected by high performance liquid chromatography using a differential refractometer as a detector.
The above maltose conversion was observed. After removing DMF in the enzyme reaction solution with a rotary evaporator, the mixture was loaded on a column (inner diameter: 5.0 cm, length: 60 cm) packed with silica gel (manufactured by Merck, Kieselgel 60), and chloroform / methanol (8: 1) was used. And the eluted fractions were collected by a fraction collector to separate the products, thereby obtaining each polymerizable sugar ester represented by the following formula.

Embedded image [C ₁₂ H ₁₄ O ₃ (OH) ₇ ] -OOC (C
_{H 2) 4 COOCH = CH 2} (12)

Embedded image In the polymerizable sugar ester of the formula ( 12 ), the substituent bonded to the sugar skeleton is bonded to 6'-0- of maltose, while in the polymerizable sugar ester of the formula ( 13 ), the substituent is bonded to the sugar skeleton. Of the two substituents, one is attached to the 6'-0-position of maltose and the other is at the 6'-0 position of maltose.
It was bonded to the -0-position.

Reference Example 2 Sucrose [C ₁₂ H ₁₄ O ₃ (OH) ₈ ] as in Example 1 .
4.28 g and 19.82 g of divinyl adipate were sufficiently dried with a molecular sieve (3A) to obtain DMF50.
dissolved in Bacillus licheniformis (Baci
The suspension was added with 250 mg of alkaline protease (promega) derived from L. licheniformis. Thereafter, the same operation as in Example 1 was performed, and as a result, a polymerizable sugar ester represented by the following formula was obtained.

Embedded image [C ₁₂ H ₁₄ O ₃ (OH) ₇ ] —OOC (C
_{H 2) 4 COOCH = CH 2} (14)

Embedded image In the polymerizable sugar ester of the formula ( 14 ), the substituent bonded to the sugar skeleton is bonded to 1′-0- of sucrose, while in the polymerizable sugar ester of the formula ( 15 ), the substituent is bonded to the sugar skeleton. Of the two substituents, one is attached to the 1'-0-position of sucrose and the other is 6-position of sucrose.
It was bonded to the -0-position.

Reference Example 3 An experiment was conducted in the same manner as in Reference Example 1 except that glucose [C ₆ H ₇ O (OH) ₅ ] was used instead of maltose, and a polymerizable sugar ester represented by the following formula was obtained. Obtained.

Embedded image [C ₆ H ₇ O (OH) ₄ ] —OOC (CH ₂ ) ₄ COOCH ＝ CH ₂ ( 16 )

Embedded image In the polymerizable sugar ester of the formula ( 16 ), the substituent bonded to the sugar skeleton is bonded to the 6-0-position of glucose, while, in the polymerizable sugar ester of the formula ( 17 ), 2 is bonded to the sugar skeleton. One of the two substituents is the 6
And the other one is 1-0- of glucose.
, 2-0-position, 3-0-position or 4-0-position.

Reference Example 4 An experiment was carried out in the same manner as in Reference Example 1 except that mannose [C ₆ H ₇ O (OH) ₅ ] was used instead of maltose as a sugar compound. Obtained.

Embedded image [C ₆ H ₇ O (OH) ₄ ] —OOC (CH ₂ ) ₄ COOCH ＝ CH ₂ ( 18 )

Embedded image In the polymerizable sugar ester of the formula ( 18 ), the substituent bonded to the sugar skeleton is bonded to the 6-O-position of mannose, while, in the polymerizable sugar ester of the formula ( 19 ), 2 is bonded to the sugar skeleton. One of the two substituents is
The other is the mannose 1-0-
, 2-0-position, 3-0-position or 4-0-position.

[0019]Reference Example 5  The polymerizable sugar ester (6′-0-azi
0.5 g of vinyl glucose pinate and AIBN (2,
2'-azoisobutyronitrile)
Dissolved in 0.5 g of tilformamide (DMF) and degassed
Sealed. This reaction solution was reacted at 60 ° C. for 24 hours.
Was. The reaction solution was dropped into chloroform with stirring.
More product was obtained. Dissolve this product in 1 ml DMF
And drop it again into chloroform to dissolve the product in water.
Lyophilization yielded 0.4 g of polymer. Average polymer content
The amount of particles was measured by GPC analysis. As a result, Mw = 1
3600, Mn = 4100, Mw / Mn = 3.3
It was confirmed that. Melting point was 90-95 ° C.

[0020]Reference example 6  The polymerizable sugar ester (6′-0-azi
0.5 g of vinyl mannose pinate) and 5 mg of AIBN
Dissolved in 1 g of distilled dimethylformamide (DMF)
After degassing, the tube was sealed. The reaction solution is left at 60 ° C. for 24 hours.
Reaction. The reaction solution is dropped into chloroform with stirring
To give the product. This product was added to 1 ml of DMF
And drop it again in chloroform, and transfer the product to water.
It was melted and freeze-dried to obtain 0.2 g of a polymer. Polymeric
The average molecular weight was determined by GPC analysis. As a result, M
w = 5400, Mn = 3100, Mw / Mn = 1.74
Was confirmed. The melting point is 90-98 ° C
Was.

[0021]Example 1  In Reference Example 5, the formula obtained in Reference Example 3 (17)
Polymerizable sugar ester having two vinyl group-containing substituents
Per 100 mol of 6'-0-vinyl adipate glucose
The experiment was carried out in the same manner except that it was added at a ratio of 2 mol.
Was. The average molecular weight Mw of the polymer obtained in this case is 2
7000, Mn is 15000, Mw / Mn
Was confirmed to be 1.8. Melting point is 100-11
0 ° C. was indicated.

[0022]Example 2 Reference example 6 In the formula obtained in Reference Example 4,19)
Polymerizable sugar ester having two vinyl group-containing substituents
Per 100 mol of vinyl mannose 6'-0-adipate
The experiment was carried out in the same manner except that it was added at a ratio of 2 mol.
Was. The average molecular weight Mw of the polymer obtained in this case is 2
3000, Mn is 12000, Mw / Mn
Was found to be 1.92. Melting point is 95-10
5 ° C was indicated.

The GPC analysis conditions are as follows. Column: TOSOH G5000PWXL + G40
00PWXL + G2500PWXL Flow rate: 1 ml / min Eluate: 0.1 M NaCl aqueous solution Temperature: 40 ° C. Injection amount: 500 μg / 100 μl Detector: Differential refractometer

[0024]Reference Example 7  0.4 g of maltose-6-0-vinyl adipate and excess
4 μl of hydrogen oxide and 0.4 mg of ferrous sulfate in 2 g of distilled water
After dissolving and degassing, the tube was sealed. This reaction solution was added at 25 ° C. for 2 hours.
The reaction was performed for 4 hours. The reaction solution is dropped into acetone with stirring
To give the product. 1 ml of this product in distilled water
Dissolved in water and dropped into acetone again to dissolve the product in water.
After freeze-drying, 0.35 g of a polymer was obtained. Polymer minute
The amount of particles was measured by GPC analysis. As a result, Mw = 5
2150, Mn = 24600, Mw / Mn = 2.1
Was confirmed. The GPC analysis conditions are as follows.
It is on the street. Flow rate: 1 ml / min Eluent: 0.1 M NaCl aqueous solution Temperature: 40 ° C. Injection amount: 500 μg / 100 μl Detector: Differential refractometer

[0025]Reference Example 8  α-methylglucoside-6-0-vinyl adipate
4 g, 4 μl of hydrogen peroxide and 0.4 mg of ferrous sulfate
Dissolved in 2 g of distilled water,Reference Example 7Do the same operation as
As a result, Mw = 18300, Mn = 7970, Mw / M
Poly (α-methylglucoside) having a molecular weight of n = 2.4
-6-0-vinyl adipate).

[0026]Reference Example 9  0.4 g of glucose-6-0-vinyl adipate and excess
4 μl of hydrogen oxide and 0.4 mg of ferrous sulfate in 2 g of distilled water
After dissolving and degassing, the tube was sealed. Since thenReference Example 7Operation similar to
As a result, Mw = 51700, Mn = 23080,
Poly (glucose-) having a molecular weight of Mw / Mn = 2.2
6-0-vinyl adipate) was obtained.

[0027]Reference example 10  Evaluating the ability of polymers with reducing sugar branching to generate active oxygen
did. Reactive sugar reduces oxygen by one-electron reduction
Nitro blue tetrazolium
It was measured by a method using (NBT). [C. BEAA
uchampand I. Fridovich, An
al. Biochem. , 44, 276-287 (19)
71)] That is, 0.015 containing 50 mM NBT
6-28 mM sugar-containing polymer or sugar in m-buffer
And reacted at 25 ° C. for 40 minutes in a glass cell.
Blue forma due to superoxide generated by BT
As a result, the absorbance is 560 nm with a spectrophotometer.
Measurement of the rate of increase of oxygen
Was.

Table 1 shows the superoxide formation rate.
Glucose and maltose were found to have an extremely high active oxygen generation rate by being polymerized. On the other hand, α-methylglucoside having no reducing end showed a low value without any change in active oxygen generating ability even when polymerized.

[0029]

[Table 1]

[0030]

The sugar-containing polymer of the present invention has a structure in which sugar is bonded to polyvinyl alcohol via a spacer made of dicarboxylic acid, and is a hydrophilic polymer having a sugar function. The sugar-containing polymer of the present invention is advantageously used as a biodegradable polymer in the field of packaging materials, the field of food, the field of medicine, and the like. Further, the reducing sugar-containing polymer of the present invention can be used as an active oxygen generator.

──────────────────────────────────────────────────続 き Continuing from the front page (72) Inventor Yu Kitagawa 2-8-11 Nishi-Shimbashi, Minato-ku, Tokyo 7th Oriental Maritime Building 8th Floor Global Environmental Innovative Technology Institute The Project Room (72) ) Inventor Yutaka Tokiwa 1-3-1 Higashi, Tsukuba, Ibaraki Pref., Institute of Biotechnology, Industrial Technology Institute (72) Inventor Yoichi Hiraguri 1-3-1, Higashi 1-Chome, Tsukuba, Ibaraki Pref., Institute of Biotechnology, Industrial Technology Institute Examiner Yoshihide Kawakami (56) References JP-A-3-124712 (JP, A) JP-A-53-92886 (JP, A) JP-A-9-143194 (JP, A) Table 7-7-503757 ( JP, A) August 2, 1995 At the Japan Society of Agricultural Chemistry held by the Japan Society of Agricultural Chemistry, the 1995 Annual Conference of the Japanese Society of Agricultural Chemistry, Shigeru Shibatani and Yutaka Tokiwa gave the title "Enzyme (58) Investigated field (Int. Cl. ⁷ , DB name) C08F 18/14-18/18 C08F 218/14- 218/18 CA (STN)

Claims (2)

(57) [Claims] 1. S (OH) q _-1 -OOC-R-COOCH = CH ₂ (1) wherein S (OH) q _-1 is a sugar skeleton S Q
A monovalent saccharide residue obtained by removing one hydroxyl group from a saccharide compound comprising two hydroxyl groups, R represents an alkylene group, and q represents 4
Or 5) is represented by the following formula:
The following general formula (2) (Wherein, S (OH) q _-2 represents a sugar skeleton S and q
A divalent saccharide residue obtained by removing two hydroxyl groups from a saccharide compound comprising two hydroxyl groups, R represents an alkylene group, and q represents 4
Or the number of 5) is obtained by a copolymerization reaction with the polymerizable sugar ester B represented by the formula (1), wherein the ratio of the polymerizable sugar ester B contained in the polymer molecule is A sugar-containing polymer having a ratio of 0.05 to 10 mol per 100 mol of ester A. 2. The sugar-containing polymer according to claim 1, wherein said S (OH) q _-1 is a sugar residue derived from glucose, mannose or galactose.