JP2002128899A - Water-absorbing polymer with biodegradability - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a water-absorbing polymer having a superior biodegradability and a high water-absorbing capability. SOLUTION: The water-absorbing polymer with biodegradability which is produced by directly cross-linking a biodegradable polyamino acid having a carboxy group on a sidechain with a biodegradable compound which contains two functional groups reacting with a carboxy group and hydrophilic groups of more than two of the same kind as the functional group or hydrophilic groups of more than one different from the functional group within the same molecule is provided. The production method for the water-absorbing high polymer with biodegradability where the cross-linking reaction is performed in an organic solvent, water or their mixed solvent by using a water soluble carbodiimide or if necessary adding a base.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a body fluid absorber and a sustained-release drug carrier in the medical field, and a water-absorbing polymer used as a soil moisture retaining material in the field of greening. 2. Description of the Related Art Demands for materials having a large amount of water absorption have been increasing mainly in the medical field, and many materials have been provided. However, many of these materials are not completely biodegradable, and have many problems with their disposal. The present invention relates to a novel water-absorbing polymer having biodegradability.

[0002]

2. Description of the Related Art It has been known that a polymer compound obtained by subjecting starch obtained by graft polymerization of acrylonitrile to alkali hydrolysis has high water absorption. However, since this polymer compound does not have biodegradability, development of a water-absorbing polymer having a skeleton of a polymer expected to be biodegradable, such as polyaspartic acid or polyglutamic acid, has been promoted.

[0003] For example, JP-A-11-5838 discloses a method for producing a crosslinked polyaspartic acid by crosslinking polysuccinimide with a carboxylic acid salt of a basic amino acid and hydrolyzing the remaining imide ring. It has been disclosed. In this case, the polyaspartic acid chain has an α-amide bond and β
It is considered that amide bonds are mixed, but it is considered that biodegradability is expected. However, the raw material polysuccinimide does not exist in nature. Also, the indirect method of passing through an imide ring is used for the method of crosslinking.

Japanese Patent Application Laid-Open No. H11-343339 discloses that poly-γ-glutamic acid is reacted with a compound having two or more functional groups capable of reacting with a carboxyl group in its side chain (hereinafter referred to as “crosslinking agent”). There is disclosed a biodegradable water-absorbent resin characterized by having been made to perform the above. However, the crosslinking agent used here is not necessarily limited to those having biodegradability. The crosslinking agents exemplified in this specification are:
Ethylene glycol diglycidyl ether, propylene glycol diglycidyl ether, glycerin-1,3
-Diglycidyl ether, polyethylene glycol diglycidyl ether, etc., and the only cross-linking agent used in the examples was ethylene glycol diglycidyl ether, and the cross-linking agent described in Table 1 was ethylene glycol diglycidyl. Only ether, diethylene glycol diglycidyl ether and polyethylene glycol diglycidyl ether. Most of them do not have biodegradability.

Japanese Patent Application Laid-Open No. 2000-63511 discloses that at least one selected from polyamino acids, polyepoxy compounds, polyols, polythiols, polyisocyanates, polyaziridines, and polyvalent metals is used as a crosslinking agent. A method for producing a crosslinked polyamino acid using the same is disclosed. However, the crosslinked polyamino acids according to the present invention are not intended to have biodegradability, and most of the crosslinkers described as requirements of the present invention have no biodegradability. is there.
The crosslinking agent of Example 1 described in this specification is lysine methyl ester, the crosslinking agent of Example 6 is hexamethylenediamine, and the crosslinking agent of Example 7 is ethylene glycol diglycyl ether. And not all are biodegradable. Examples 2 to 5 correspond to Example 1.
In this case, the sorbitol and chitosan fine particles used are not used as a crosslinking agent.

[0006]

The problem to be solved by the present invention is that not only a polymer having a biodegradable skeleton polymer but also a crosslinking agent having a biodegradable property is used. An object of the present invention is to develop a water-absorbing polymer having excellent biodegradability and high water absorbability by directly cross-linking the polymer.

[0007]

Means for Solving the Problems In order to solve the above-mentioned problems, the present inventors have developed a biodegradable polyamino acid having a carboxyl group in a side chain by two functional groups which react with a carboxyl group in the same molecule. A biodegradable compound having a group and two or more hydrophilic groups of the same type as this functional group or one or more hydrophilic groups different from this functional group, and having a biodegradable water absorption characteristic of being directly crosslinked. A polymer (hereinafter referred to as a “first invention”), in the first invention, two functional groups that react with a carboxyl group in the same molecule, two or more hydrophilic groups of the same type as the functional group, or different types of the functional group The biodegradable compound having at least one hydrophilic group is a saccharide, a biodegradable water-absorbing polymer (hereinafter referred to as “second invention”). Degradable polyamino acid is poly-γ-glu A biodegradable water-absorbing polymer (hereinafter referred to as "third invention"), which is a minic acid, a biodegradable polyamino acid having a carboxyl group in a side chain is converted into two functional groups that react with a carboxyl group in the same molecule. Group and two or more hydrophilic groups of the same type as this functional group or 1
The reaction of directly cross-linking with a biodegradable compound having two or more hydrophilic groups, in an organic solvent, water, or a mixed solvent thereof,
A method for producing a biodegradable water-absorbing polymer according to the first to third inventions (hereinafter referred to as "fourth invention"), wherein the method is performed using a water-soluble carbodiimide; and
A biodegradable polyamino acid having a carboxyl group in the side chain is directly ester-bonded to a saccharide to form a cross-linking reaction in an organic solvent, water, or a mixed solvent thereof using a water-soluble carbodiimide and a base. And a method for producing a biodegradable water-absorbing polymer according to the second invention (hereinafter referred to as "fifth invention").

The water-absorbing polymer according to the first invention is characterized in that a biodegradable polyamino acid having a carboxyl group in a side chain (hereinafter abbreviated as “backbone polyamino acid”) is converted into two carboxyl groups in the same molecule. Direct cross-linking with a biodegradable compound having a functional group and two or more hydrophilic groups of the same type as this functional group or one or more hydrophilic groups different from this functional group (hereinafter abbreviated as “cross-linking compound”) Features. Skeletal polyamino acids include homopolymers of naturally occurring monoaminodicarboxylic acids such as aspartic acid and glutamic acid,
And copolymers of both, and copolymers of these monoaminodicarboxylic acids with naturally occurring monoaminomonocarboxylic acids such as glycine, alanine, valine, leucine, and isoleucine. Can be.

[0009] Some backbone polyamino acids are biosynthesized by microorganisms. For example, poly-γ-glutamic acid is produced by fermentation of several kinds of microorganisms represented by Bacillus natto, and those microorganisms also produce those having a molecular weight of 1,000,000 or more.

In the cross-linking compound, examples of the functional group that reacts with a carboxyl group include a hydroxyl group that forms an ester bond with a carboxyl group and an amino group that forms an amide bond with a carboxyl group. The hydrophilic group includes a carboxyl group or a hydroxyl group. And the like. However, in the crosslinked compound, when the functional group that reacts with the carboxyl group of the skeleton polyamino acid and the hydrophilic group are the same kind, for example, when the functional group that reacts with the skeleton polyamino acid is a hydroxyl group and the hydrophilic group is also a hydroxyl group, In addition to the two hydroxyl groups that form an ester bond with an amino acid, two or more hydroxyl groups are required as a hydrophilic group. It is considered that the reason is that a part of the hydroxyl group considered as a hydrophilic group of the cross-linking compound also forms an ester bond with the skeleton polyamino acid and is consumed in the cross-linking reaction.
In such a case, generally, the larger the number of hydrophilic groups that do not react with the backbone polyamino acid, the higher the water absorption. For example,
Of the naturally occurring saccharides, the monosaccharide fructose does not have a high water absorption, but the disaccharide lactose has a high water absorption, and the cyclodextrin has a much higher water absorption.

Further, in the case where the functional group reacting with the carboxyl group of the backbone polyamino acid and the hydrophilic group are different from each other, for example, the cross-linking compound has an amino group as the functional group reacting with the carboxyl group and a carboxyl group as the hydrophilic group. When it has, it is sufficient that at least one hydrophilic group is provided. It is considered that the reason is that there is no possibility that the hydrophilic group is consumed in the crosslinking reaction with the backbone polyamino acid. Examples of such a crosslinking compound include naturally occurring diaminomonocarboxylic acids such as lysine and ornithine.
And, although these compounds have only one carboxyl group as a hydrophilic group in addition to the two amino groups that react with the carboxyl group, the polymer cross-linked with these compounds is All have very high water absorption.

Further, as the cross-linking compound, water-soluble chitosan obtained by deacetylating chitin, which is a polysaccharide composed of amino sugars, can be mentioned. It is considered that this water-soluble chitosan is cross-linked by an ester bond of a hydroxyl group of a sugar or an amide bond of an amino group generated from an acetylamide group. And since these compounds have many hydrophilic groups, when crosslinked with these compounds, very high water absorption is obtained in each case.

The term "direct cross-linking" refers to cross-linking a biodegradable skeleton polyamino acid and a cross-linking compound without a pretreatment without using a starting material whose presence or absence of biodegradability is not clear in the production process. Thereby, a water-absorbing polymer having biodegradability can be produced. Therefore,
The method of crosslinking a water-absorbing polymer according to the present invention is disclosed in
It does not include the method for producing crosslinked polyaspartic acid via polysuccinimide disclosed in Japanese Patent No. 1-5838.

The water-absorbing polymer according to the second invention is a biodegradable water-absorbing polymer in which the crosslinking compound of the first invention is limited to saccharides. This saccharide includes monosaccharide fructose, disaccharide lactose, cyclic oligosaccharide cyclodextrin, and the like, and further includes chitosan obtained from a polysaccharide composed of an amino sugar.

The water-absorbing polymer according to the third invention is a water-absorbing polymer in which the backbone polyamino acid of the first invention is limited to poly-γ-glutamic acid. As described above, this poly-γ-glutamic acid is produced by fermentation of several kinds of microorganisms represented by Bacillus natto.

The method for producing a water-absorbing polymer according to the fourth invention is characterized in that in the reaction for directly crosslinking a backbone polyamino acid with a crosslinking compound, a water-soluble carbodiimide is used in an organic solvent, water or a mixed solvent thereof. It is characterized by reacting. The solvent used here may be any one that can dissolve, swell, or disperse a biodegradable polyamino acid having a carboxyl group in a side chain such as poly-γ-glutamic acid. Well, usually, water,
Organic solvents or mixtures thereof are used. However, in order to obtain a high yield, an organic solvent that can dissolve the skeleton polyamino acid, particularly a polar organic solvent, is preferable. Among them, dimethyl sulfoxide is most preferable.

The condensing agent used for the crosslinking reaction is preferably a water-soluble carbodiimide. The carbodiimide is not particularly limited as long as it can be dissolved in the reaction solvent. However, from the viewpoint of low toxicity and easy purification after the reaction, 3
-(3-Dimethylaminopropyl) -1-ethylcarbodiimide hydrochloride is suitable.

The method for producing a water-absorbing polymer according to the fifth invention is characterized in that the reaction for crosslinking the backbone polyamino acid with a saccharide comprises:
The method is characterized in that the reaction is carried out using a water-soluble carbodiimide and a base in an organic solvent, water, or a mixed solvent thereof. As the base, any of an inorganic base and an organic base can be used. Among them, when used in an organic solvent, those having strong basicity that are soluble in an organic solvent, such as 4-dimethylaminopyridine and 4-pyrrolidinopyridine, are suitable.

[0019]

BEST MODE FOR CARRYING OUT THE INVENTION Production of Water Absorbent Polymer [Example 1] Poly-γ-glutamic acid (hereinafter referred to as “γ-PG
A) and 9.4 mg of 4-dimethylaminopyridine (hereinafter abbreviated as “DMAP”) were placed in a 15 ml screw-cap test tube, and dimethyl sulfoxide (hereinafter abbreviated as “DMS”).
O ") was added and stirred. Then D-
DMSO solution in which 34.9 mg of fructose was dissolved.
1 ml was added and stirred to dissolve the whole. To this 3-
80 mg of (3-dimethylaminopropyl) -1-ethylcarbodiimide hydrochloride (hereinafter abbreviated as “WSC”) was added and stirred. After reacting at room temperature for 24 hours, acetone was added to wash the reaction product to remove DMSO and DMAP. A phosphate buffer of pH 7.2 was added to the obtained white precipitate to swell overnight, and then the pH of the solution was adjusted to 8 by adding a 1 M aqueous sodium hydroxide solution. The solution containing this gel
It was placed in a 5-mesh nylon bag, soaked in distilled water, and sufficiently washed. Thereafter, the nylon bag was pulled out, drained, and the remaining gel was freeze-dried to obtain 120.1 mg of powder (hereinafter, referred to as “compound 1”). The yield after the drying of the obtained water-absorbing polymer (compounds 1 to 10) with respect to the sum of the weight of the γ-PGA used for the reaction and the weight of the cross-linking compound was determined based on the yield used in this example and the subsequent examples. The yield was 89%.

Example 2 100 mg of γ-PGA and DM
Place 9.4 mg of AP in a 15 ml screw cap test tube, and add DMS
0.3 ml of O was added and stirred. Then lactose 6
0.4 ml of DMSO solution in which 9.8 mg was dissolved was added and stirred to dissolve the whole. To this was added 0.3 ml of DMSO in which 80 mg of WSC was dissolved, and the mixture was reacted at room temperature for 24 hours. Thereafter, the same treatment as in Example 1 was performed to obtain 147 g of a powder (hereinafter, referred to as “compound 2”). The yield was 87%.

Example 3 γ-PGA 100 mg, DM
9. 9.4 mg of AP and α-cyclodextrin
9 mg was placed in a 15 ml screw test tube, and DMSO 0.7
ml was added and stirred to dissolve the whole. To this WSC8
0.3 ml of DMSO in which 0 mg was dissolved was added, and the mixture was added at room temperature for 2 minutes.
The reaction was performed for 4 hours. Thereafter, the same treatment as in Example 1 was performed to obtain 107.4 mg of a powder (hereinafter, referred to as “compound 3”).
The yield was 90%.

Example 4 γ-PGA 100 mg and DM
Place 9.4 mg of AP in a 15 ml screw cap test tube, and add DMS
0.5 ml of O was added and stirred, and then 0.06 m of a DMSO solution in which 43.6 mg of β-cyclodextrin was dissolved.
and stirred to dissolve the whole. This is WSC80m
g of DMSO solution in which 0.3 g was dissolved.
The reaction was performed for 6 hours. Thereafter, the same treatment as in Example 1 was carried out to obtain 96.5 mg of powder (hereinafter, referred to as "compound 4"). The yield was 67%.

Example 5 γ-PGA 100 mg, DM
AP 9.4 mg and γ-cyclodextrin 25.
1 mg was placed in a 15 ml screw test tube, and DMSO 0.7
ml was added and stirred to dissolve. Then, WSC80m
g of DMSO solution in which 0.3 g was dissolved.
The reaction was performed for 4 hours. Thereafter, the same treatment as in Example 1 was performed to obtain 92.1 mg of powder (hereinafter, referred to as “compound 5”). The yield was 73.6%.

Example 6 50 mg of γ-PGA was added to 15 m
1 into a screw test tube, add 0.5 ml of DMSO, stir and dissolve. Next, DM in which 40 mg of WSC was dissolved
0.15 ml of SO solution was added and stirred. In addition, L-
17.7 mg of lysine monohydrochloride was dissolved, 80 μl of an aqueous solution adjusted to pH 9 with a 1 M aqueous sodium hydroxide solution was added, and the mixture was reacted at room temperature for 24 hours. Thereafter, the same treatment as in Example 1 was carried out to obtain a powder (hereinafter referred to as “compound 6”) 60.1 m
g was obtained. The yield was 88.8%.

Example 7 50 mg of γ-PGA was added to 15 m
1 into a screw test tube, add 0.5 ml of DMSO, stir and dissolve. Next, DM in which 40 mg of WSC was dissolved
0.15 ml of SO solution was added and stirred. In addition, L-
16.3 mg of ornithine monohydrochloride was dissolved, and 80 µl of an aqueous solution adjusted to pH 8 with a 1 M aqueous sodium hydroxide solution was added thereto, followed by reaction at room temperature for 24 hours. Thereafter, the same treatment as in Example 1 was carried out to obtain a powder (hereinafter referred to as “compound 7”) 50.2 m
g was obtained. The yield was 75.7%.

Example 8 50 mg of γ-PGA was added to 15 m
1 The test tube was placed in a screw-cap test tube, and 0.5 ml of DMSO was added thereto and dissolved by stirring. Next, DMS in which 40 mg of WSC was dissolved
0.15 ml of O solution was added and stirred. To this was added 77.4 μl of an aqueous solution in which 15.6 mg of water-soluble chitosan was dissolved, and the mixture was reacted at room temperature for 24 hours. Thereafter, the powder was treated in the same manner as in Example 1 to obtain a powder (hereinafter, referred to as “compound 8”) 70.9 mg
I got The yield was 70.9%.

Example 9 50 mg of γ-PGA was added to 15 m
The mixture was placed in a 1-neck screw test tube, and 0.194 ml of a 1 M aqueous sodium hydroxide solution was added to dissolve the mixture. This is WSC 40m
g was added and stirred. Furthermore, water-soluble chitosan 15.6m
Then, 77.4 μl of an aqueous solution in which g was dissolved was added and reacted at room temperature for 24 hours. Thereafter, the same treatment as in Example 1 was performed to obtain 17 mg of powder (hereinafter, referred to as “compound 9”). The yield is 25.
9%.

Comparative Example γ-PGA 100 mg, DMA
P9.4 mg and glycerin 17.8 mg
ml screw test tube, add 0.7 ml of DMSO,
Stir to dissolve. Next, 0.3 ml of DMSO in which 80 mg of WSC was dissolved was added, and reacted at room temperature for 24 hours. Thereafter, the same treatment as in Example 1 was carried out to obtain 119 mg of powder (hereinafter, referred to as "compound 10"). The yield was 100%.

2. Water Absorption Test The compounds 1 to 9 obtained in Examples 1 to 9 and the compound 10 obtained in Comparative Example were subjected to a water absorption test according to the method described in JIS K7223. That is,
The previously dried compounds 1 to 10 were each weighed to 2
Placed in a 55 mesh nylon bag, immersed in excess distilled water for 24 hours, drained for 10 minutes, measured the weight of each, and determined the weight of each of the dried compounds 1 to 10 from the obtained weight. After subtraction, the weight of the empty nylon bag immersed in distilled water for 24 hours and drained for 10 minutes was subtracted to obtain the weight of the absorbed water for each of the compounds 1 to 10, and the weight of the water was determined as the dried compound. The water absorption was calculated by dividing the weight by 1 to 10 respectively. The amount of water absorption thus obtained was as shown in Table 1.

[0030]

[Table 1]

As shown in Table 1, when a natural saccharide is used as the cross-linking compound, the functional group and the hydrophilic group are the same, and two functional groups in the same molecule are hydroxyl groups.
The number of hydrophilic groups is also a hydroxyl group, but it can be seen that the water absorption increases as the number of hydrophilic groups in the same molecule increases. That is, the water absorption is not so high for the monosaccharide fructose, but increases for the disaccharide lactose, and dramatically increases for the cyclodextrin. As described above, it is considered that the reason why the water absorption of cyclodextrin is very high is that the number of hydroxyl groups is particularly large as compared with monosaccharides and disaccharides. In addition, water-soluble chitosan also has high water absorption, which is considered to be due to having many hydrophilic groups in the same molecule. In addition, when glycerin is used for cross-linking of the skeleton polyamino acid, it is understood that the water absorption is not so high. It is considered that the reason for this is that not only the two hydroxyl groups of glycerin but also the third hydroxyl group are partially used for crosslinking, and free hydroxyl groups are reduced.

As shown in Table 1, when the functional group and the hydrophilic group are different, that is, when lysine or ornithine in which two functional groups are amino groups and the hydrophilic group is one carboxyl group. It can be seen that has a high water absorption even with only one hydrophilic group. This is considered to be because the hydrophilic group is not consumed in the crosslinking reaction during the crosslinking reaction.

[0033]

As described above, the biodegradable water-absorbing polymer according to the present invention has the above-described structure and characteristics, and thus it is clear that it has excellent biodegradability and high water absorption. . In addition, the method for producing a biodegradable water-absorbing polymer according to the present invention enables the production of such a polymer for the first time. Therefore, the present invention is applicable not only to a wide range of fields such as a body fluid absorber and a sustained-release drug carrier in the medical field, and a soil water retention material in a greening field, but also solves problems related to treatment after use. It can do so and contribute significantly to the development of related industries and the protection of the environment.

Claims (5)

[Claims] 1. A biodegradable polyamino acid having a carboxyl group in a side chain is obtained by preparing two functional groups which react with a carboxyl group in the same molecule and two or more hydrophilic groups of the same type as the functional group or this functional group. And a biodegradable compound having at least one hydrophilic group different from the above, and a biodegradable water-absorbing polymer characterized by being directly crosslinked. 2. A biodegradable compound having two functional groups that react with a carboxyl group and two or more hydrophilic groups of the same type as the functional group or one or more hydrophilic groups different from the functional group in the same molecule. The biodegradable water-absorbing polymer according to claim 1, wherein is a saccharide. 3. The biodegradable polyamino acid having a carboxyl group in a side chain is poly-γ-glutamic acid.
Biodegradable water-absorbing polymer as described 4. A biodegradable polyamino acid having a carboxyl group in a side chain is obtained by reacting two functional groups which react with a carboxyl group in the same molecule with two or more hydrophilic groups of the same type as the functional group or this functional group. And a biodegradable compound having one or more hydrophilic groups different from those described above, wherein a reaction for directly crosslinking is performed using a water-soluble carbodiimide in an organic solvent, water, or a mixed solvent thereof. Claims 1 to 3
PROCESS FOR PRODUCING WATER ABSORPTION POLYMER HAVING BIODEGRADE 5. A cross-linking reaction in which a biodegradable polyamino acid having a carboxyl group in a side chain is directly ester-bonded to a saccharide to form an organic solvent, water, or a mixed solvent thereof.
3. The method for producing a biodegradable water-absorbing polymer according to claim 2, wherein the method is performed using a water-soluble carbodiimide and a base.