JP2006282926A - Water-soluble polyuronic acid and its production method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing a highly water-soluble polyuronic acid in an aqueous solvent with retention of such advantages originated from polysaccharides as less adverse influence upon surroundings and human bodies. <P>SOLUTION: The water-soluble polyuronic acid shown by the chemical formulas (1) to (3) can be produced in an aqueous solvent at least by a process of oxidizing selectively a polysaccharide, a process of adding a polyvalent cation to the oxidized polysaccharide to produce a water-insoluble product, a process of washing the water-insoluble product with an aqueous solvent and a process of ion-exchanging the water-insoluble product washed with an aqueous solvent. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

The present invention relates to a production method for producing polyuronic acid having a uniform structure derived from a polysaccharide using water or an aqueous solvent mainly composed of water.

In recent years, natural polysaccharides have attracted attention as new types of biodegradable polymer materials and biocompatible materials, and many studies have been made on their use. Among natural polysaccharides, cellulose and chitin are hardly soluble in water and other common solvents, and their use has been limited, but various derivatizations have been invented, and organic solvents such as acetone and chloroform In addition, methods that dissolve in water have been developed. However, these derivatives have a non-uniform distribution of substituents, and synthesized derivatives are composed of monosaccharides that do not exist in nature, so that the introduced substituents may affect the environment and the living body. There were some problems.

Therefore, recently, a method has been invented in which a polysaccharide is oxidized in the presence of an N-oxyl compound catalyst to obtain water-soluble polyuronic acid. This oxidation method is a system in which a polysaccharide is dispersed in water or dissolved in an aqueous system such as 2,2,6,6-tetramethyl-1-piperidinyloxy radical (TEMPO) and sodium hypochlorite. The polysaccharide is oxidized while sequentially producing oxoammonium salts in the system using an oxidizing agent.

It is applied to various polysaccharides such as cellulose and chitin from water-soluble polysaccharides such as starch and pullulan. The polysaccharide thus oxidized has a polyuronic acid type structure in which only the primary hydroxyl group is oxidized with high selectivity and converted to a carboxyl group or a salt thereof. Since this synthetic polyuronic acid has a uniform structure composed of naturally occurring sugars and has high water solubility, various reports have been made on its effectiveness.

Oxidation of polysaccharides using the above N-oxyl compound as a catalyst is carried out by using a catalyst such as sodium bromide in addition to an N-oxyl compound such as TEMPO in an aqueous reaction solution, such as sodium hypochlorite. Oxidation proceeds with the co-oxidant.

As the oxidation progresses and the carboxyl group (sodium salt) increases, water-soluble polysaccharides such as starch as well as poorly soluble polysaccharides such as cellulose and chitin are imparted with hydrophilicity and solubilized in water.

After completion of the reaction, the reaction aqueous solution is generally dropped into a poor solvent such as ethanol to precipitate the water-soluble oxidized polysaccharide. After isolation, in order to remove sodium chloride and other reagents generated in the course of the reaction, washing with an organic solvent containing water is repeated, and finally, dehydration with acetone is performed followed by drying.

In this case, the reaction itself is an aqueous reaction, but a large amount of an organic solvent is used for isolation and purification.
Alternatively, the reaction aqueous solution is subjected to dialysis, and the aqueous solution after dialysis is freeze-dried. However, the treatment becomes large, the use is limited, and it is not suitable for mass production.
JP 2004-189924 A

An object of the present invention is to provide a method for producing polyuronic acid having a high water solubility and an aqueous solution thereof with an aqueous solvent while taking advantage of the inherent advantage of polysaccharides that have less adverse effects on the environment and the human body.

The invention according to claim 1 includes at least a step of selectively oxidizing a polysaccharide, a step of adding a polyvalent cation to the oxidized polysaccharide to produce a water-insolubilized product, and an aqueous system of the water-insolubilized product. A method for producing a water-soluble polyuronic acid represented by any one of chemical formulas (1) to (3), comprising a step of washing with a solvent and a step of ion-exchange the water-insolubilized product.

The invention according to claim 2 is characterized in that in the oxidation step, the polysaccharide is dispersed or dissolved in an aqueous system and oxidized using a co-oxidant in the presence of an N-oxyl compound. The method for producing a water-soluble polyuronic acid described in 1.

The invention according to claim 3 is the method for producing water-soluble polyuronic acid according to any one of claims 1 to 2, wherein the polyvalent cation is a metal salt.

The invention according to claim 4 is the method for producing water-soluble polyuronic acid according to claim 3, wherein the polyvalent cation is an alkaline earth metal salt.

The invention according to claim 5 is the method for producing water-soluble polyuronic acid according to claim 4, wherein the alkaline earth metal salt is a calcium salt.

The invention according to claim 6 is the method for producing water-soluble polyuronic acid according to any one of claims 1 to 2, wherein the polyvalent cation is a polyamine.

The invention according to claim 7 is any one of claims 1 to 6, wherein the polysaccharide is one or a mixture of two or more selected from starch, cellulose, chitin, chitosan, and pullulan. A method for producing a water-soluble polyuronic acid according to claim 1.

The invention according to claim 8 is the method for producing water-soluble polyuronic acid according to any one of claims 1 to 7, wherein the aqueous solvent is water or a solvent mainly composed of water. is there.

The invention according to claim 9 is characterized in that, in the ion exchange step, the suspension of polyuronic acid polyvalent cation salt is ion-exchanged through an ion exchange resin to be water-solubilized again. 8. The method for producing a water-soluble polyuronic acid according to any one of 8 above.

The invention according to claim 10 is a water-soluble polyuronic acid produced by the production method according to any one of claims 1 to 9.

According to the production method of the present invention, it is possible to produce a polyuronic acid having a uronic acid structure with a controlled chemical structure and imparting hydrophilicity derived from a natural polysaccharide with an aqueous solvent.

In addition, the production of an aqueous solvent increases the safety of the product, and ion exchange results in the production of polyuronic acid with good water solubility. It can be used as medical materials, medicines, foods, hygiene products, cosmetics, and the like.

The present invention is described in detail below.
The water-soluble or water-dispersible polysaccharide having a uronic acid residue prepared by the production method of the present invention can be obtained by oxidizing a polysaccharide. As the polysaccharide before being oxidized, water-soluble polysaccharides such as starch, pullulan, and hyaluronic acid, and cellulose and chitin can be used. In consideration of the procurement of raw materials, costs, expected functions, and the advantage of being water-soluble with almost no change in structure, it is more preferable to use starch, cellulose and chitin.

When a highly crystalline polysaccharide such as cellulose or chitin is used as a raw material, it is preferable to perform a treatment for reducing crystallinity such as a regeneration treatment as a pretreatment. As the regeneration treatment of cellulose, a known regeneration treatment method such as a cupra ammonium method or a viscose method can be used. In addition, the chitin regeneration treatment is not limited as long as the crystallinity of the chitin after regeneration is reduced. However, in consideration of subsequent use, etc., molecular regeneration occurs due to the regeneration treatment. That is not preferable. Thus, for example, alkali regeneration treatment can be mentioned.

After dipping chitin in a high-concentration alkali, it becomes a viscous liquid by diluting under low temperature while adding ice. When neutralized by adding hydrochloric acid thereto, flaky chitin precipitates. The obtained chitin is almost amorphous, and it is washed thoroughly with water and not dried or freeze-dried, and then subjected to an oxidation reaction to suppress molecular weight reduction as much as possible, and almost all pyranose rings 6 Only primary hydroxyl groups can be oxidized to carboxyl groups.

Alternatively, chitosan which is a deacetylated product of chitin may be used as a raw material, and a material that is N-acetylated under a uniform reaction may be subjected to an oxidation reaction. For example, after dissolving chitosan in acetic acid and diluting with methanol, it is easily N-acetylated by adding 1.5 to 3 times the molar amount of acetic anhydride relative to the amount of amino groups in the chitosan, and again chitin The chemical structure can be restored.

By passing through this operation, the well-washed water is not dried or freeze-dried and subjected to an oxidation reaction, so that only the primary hydroxyl group at the 6-position is oxidized with high selectivity as in the case of alkali-regenerated chitin.

Furthermore, in this case, it is also possible to control the degree of N-acetylation of the oxidation raw material by the amount of acetic anhydride added.

As an oxidation method for obtaining polyuronic acid by oxidation of such a polysaccharide, an oxidation method should be employed which has a high selectivity to oxidation of primary hydroxyl groups and can obtain a uniform structure as much as possible, in the presence of an N-oxyl compound. A method using a co-oxidant is preferable.

This selective oxidation method can control the degree of oxidation, and can oxidize almost all the 6-positions of the pyranose ring to a carboxyl group without oxidizing the 2-position or 3-position of the pyranose ring. Moreover, it is possible to perform an oxidation reaction in an aqueous system.

As the N-oxyl compound, 2,2,6,6-tetramethyl-1-piperidine-N-oxyl (hereinafter, TEMPO) is preferably used.

In addition, as the oxidizing agent, a target oxidation reaction such as halogen, hypohalous acid, halous acid or perhalogenic acid, or a salt thereof, halogen oxide, nitrogen oxide, or peroxide can be promoted. Any oxidizing agent can be used as long as it is an oxidizing agent.

Furthermore, it is more preferable to carry out the oxidation reaction in the presence of bromide or iodide because the oxidation reaction can proceed smoothly even under mild conditions and the introduction efficiency of carboxyl groups can be greatly improved. It is particularly preferable that TEMPO is used for the N-oxyl compound and the oxidation reaction is performed using sodium hypochlorite as an oxidizing agent in the presence of sodium bromide.

Here, the amount of the N-oxyl compound is sufficient as a catalyst. For example, 10 ppm to 5% (ppc) is sufficient with respect to the number of moles of the constituent monosaccharide of the polysaccharide, but 0.05 to 3% is sufficient. More preferred.

The amount of bromide or iodide used can be selected within a range that can promote the oxidation reaction. For example, it is 0 to 100%, more preferably 1 to 50%, based on the number of moles of the constituent monosaccharide of the polysaccharide. is there.

In addition, for the purpose of improving the selectivity of oxidation of the constituent monosaccharides to primary hydroxyl groups and suppressing side reactions, it is desirable that the reaction temperature is room temperature or lower, more preferably 5 ° C. or lower. Furthermore, it is preferable to keep the inside of the system alkaline during the reaction. At this time, the pH is preferably 9 to 12, more preferably 10 to 11.

Further, in this oxidation method, the degree of oxidation can be controlled by the amount of the oxidant and the amount of alkali added when the pH is kept constant. For example, when an alkali is added in an equimolar amount with a sugar residue, almost all primary hydroxyl groups at the 6-position of the pyranose ring are oxidized to carboxyl groups, and water-soluble polyuronic acid is obtained.

For example, polyuronic acid obtained from starch has α-1,4-glucopyranose and α-1,4-glucuronic acid as constituent monosaccharides, and polyuronic acid obtained from cellulose is β-1,4-glucopyranose and β -1,4-glucuronic acid as a constituent monosaccharide, and polyuronic acid obtained from chitin is β-1,4-glucosamine and β-1,4-N-acetylglucosamine and β-1,4-glucosamineuronic acid and β- It has 1,4-N-acetylglucosaminuronic acid as a constituent monosaccharide. Hereinafter, these polyuronic acids are referred to as aminouronic acid, cellouronic acid, and chitouronic acid in this order.

Thus, for example, in an aqueous solution containing a catalytic amount of sodium bromide and TEMPO, sodium hypochlorite is used as a co-oxidant, pH is adjusted using sodium hydroxide, and an oxidation treatment is performed in an alkaline system. The resulting polyuronic acid is dissolved in water as a sodium salt of a carboxyl group.

Next, a process of insolubilizing the produced polyuronic acid with a polyvalent cation and washing with water will be described. The polyvalent cation used here is not particularly limited as long as it exchanges the counter ion of the carboxyl group present in the reaction product and precipitates or gels, that is, becomes insoluble in water. , Magnesium, aluminum, silica, titanium, vanadium, manganese, iron, cobalt, nickel, copper, zinc, silver, barium, various metal salts including alkaline earth metal salts, or organic polyvalent cations such as polyamine And can be freely selected depending on the application and required physical properties.

For example, a polyvalent metal such as copper, silver, or zinc is selected for use for the purpose of imparting antibacterial properties.

However, a calcium salt is particularly preferable from the viewpoints of product safety, ease of subsequent desalting, cost, and the like. Further, as the calcium salt, water-soluble calcium salts such as calcium chloride, calcium lactate, calcium gluconate, calcium nitrate, calcium citrate and calcium acetate are preferable from the viewpoint of removing excess calcium salt in the washing process.

The method for insolubilizing in water with a polyvalent cation is not particularly limited. For example, an aqueous solution containing a sufficient amount of the above cation is prepared with respect to the amount of polyuronic acid carboxyl groups, and the aqueous solution containing polyuronic acid is contained in the aqueous solution system. Added. Taking the case where a calcium salt is used as the polyvalent cation as an example, the polyuronic acid present as a sodium salt is converted into water-insolubilized product by replacing sodium with calcium.

Further, before the step of generating the water-insolubilized product, a step of filtering the reaction solution to remove impurities such as undissolved substances that are insufficiently reacted may be performed.

Next, this water-insolubilized product (polyuronic acid salt) is sufficiently washed with an aqueous solvent. The polyuronic acid salt insolubilized with the polyvalent cation salt of the present invention has a structure in which the carboxyl group of the polymer is cross-linked via a cation, and is insoluble in water, so there is little loss due to outflow even when washing with an aqueous solvent, Cleaning can be easily performed by decantation or filtration. Such washing with an aqueous solvent can remove reagents used in the oxidation reaction, generated salts, excess calcium salts, and the like.

The washing aqueous solvent may contain not only pure ion exchange water and distilled water but also organic solvents such as various alcohols, ketones and ethers in order to suppress swelling of the polyuronic acid salt. The amount of the organic solvent contained at this time is preferably less than 0 to less than 50 with respect to the cleaning liquid 100 by weight ratio. If it is more than this, the removal efficiency of the reaction by-products such as salts is poor, more preferably a system having an organic solvent of 40 or less is preferred, and the amount of the organic solvent is less in order to reduce the environmental load and increase the removal efficiency It is preferable that it is 20 or less.

Here, the isolated calcium polyuronic acid salt has a stable structure, and a dry powder can be stored as well as a slurry state. For drying, various methods such as air drying, heat drying, spray drying, reduced pressure drying, freeze drying and the like can be used.

Next, the ion exchange process will be described. Na, K, H, NH ₂ , metal salt of polyuronic acid obtained by the above oxidation method and washing step, for example, calcium salt (COOCa type) is dispersed in water and treated with an ion exchange resin. Water-soluble polyglucuronic acid ion-exchanged mainly into monovalent salts such as Li can be obtained.

Considering that all treatments are carried out with an aqueous solvent, this method using an ion exchange resin is preferable, and a product obtained by separating an ion exchange resin from a treated aqueous solution can be used as an aqueous solution as it is. Moreover, the solid substance of polyuronic acid can be obtained by drying this aqueous solution by various drying methods.

Furthermore, in the production method of the present invention, there is almost no loss due to the outflow or adsorption of the product in the washing or ion exchange step, and highly purified water-soluble polyuronic acid can be obtained in high yield.

EXAMPLES Hereinafter, although this invention is demonstrated in detail based on an Example, the technical scope of this invention is not limited to these embodiment.

(Preparation of chitouronic acid)
Daiichi Seika Kogyo Co., Ltd. Daichitosan 100D (VL) was used as 100% deacetylated chitosan. 10 g of this chitosan was dissolved in 190 g of 10% acetic acid, diluted with 1 L of methanol, and acetic anhydride with stirring. When 12.68 g was added, it gelled in a few minutes. After standing for 15 hours, 1 L of methanol was further added and stirred with a homogenizer, and 2N-NaOH aqueous solution was added to neutralize to pH 7. This was filtered, washed thoroughly with methanol and deionized water, and then frozen. It was dried to obtain 11.6 g of N-acetylated chitosan. The degree of N-acetylation by elemental analysis was 95%.

10 g of the prepared N-acetylated chitosan was suspended in 200 g of distilled water, and a solution in which 0.1 g of TEMPO and 2.0 g of sodium bromide were dissolved in 100 g of distilled water was added and cooled to 5 ° C. or lower. 84 g of an aqueous 11% sodium hypochlorite solution was added dropwise thereto to initiate the oxidation reaction. The reaction temperature was always kept below 5 ° C. During the reaction, the pH in the system was lowered, but a 0.5 N NaOH aqueous solution was sequentially added to adjust the pH to 10.75.

Then, when the alkali addition amount corresponding to the mole number of 100% with respect to the total mole number of the primary hydroxyl group at the 6-position was reached, ethanol was added to stop the reaction.

When an aqueous solution in which 30 g of calcium chloride was previously dissolved in 200 g of water was added to the system, a white water insolubilized product was formed. This water-insolubilized product was washed repeatedly with water containing 30% ethanol to obtain calcium chitouronic acid salt. This was further suspended in 100 g of water, and passed through a column packed with 100 mL of an ion exchange resin (organo Corporation: Amberlite IR120) to perform an ion exchange treatment. This aqueous chitouronic acid solution was freeze-dried to obtain 11.5 g of a white powder of sodium chitouronic acid.

(Preparation of amylouronic acid)
10 g of starch was dissolved by heating in 200 g of distilled water and cooled. A solution prepared by dissolving 0.18 g of TEMPO and 2.5 g of sodium bromide in 100 g of distilled water was added to this solution, and 104 g of an 11% strength sodium hypochlorite aqueous solution was added dropwise to initiate the oxidation reaction.

The reaction temperature was always kept below 5 ° C. During the reaction, the pH in the system was lowered, but a 0.5 N NaOH aqueous solution was sequentially added to adjust the pH to 10.75. Then, when the alkali addition amount corresponding to the mole number of 100% with respect to the total mole number of the primary hydroxyl group at the 6-position was reached, ethanol was added to stop the reaction.

When an aqueous solution in which 11 g of calcium chloride was previously dissolved in 100 g of water was added to the system, a white water insolubilized product was formed. This water-insolubilized product was repeatedly washed with distilled water to obtain calcium amylouronate.

The obtained calcium amylouronate was suspended in 100 g of water, and passed through a column filled with 100 mL of an ion exchange resin (Amberlite IR120 manufactured by Organo Corp.) for ion exchange treatment. The resulting aqueous amylouronate solution was lyophilized to obtain 11.8 g of amylouronate sodium salt as a white powder.

(Preparation of cellouronic acid)
As the regenerated cellulose, Benise manufactured by Asahi Kasei Kogyo Co., Ltd. is used. 10 g of regenerated cellulose is suspended in 200 g of distilled water. Until cooled.

To this, 104 g of an aqueous 11% sodium hypochlorite solution was added dropwise to initiate the oxidation reaction.

The reaction temperature was always kept below 5 ° C. During the reaction, the pH in the system was lowered, but 0.5N-NaOH aqueous solution was sequentially added to adjust the pH to 10.75. Then, when the alkali addition amount corresponding to the mole number of 100% with respect to the total mole number of the primary hydroxyl group at the 6-position was reached, ethanol was added to stop the reaction.

When an aqueous solution in which 20 g of calcium chloride was previously dissolved in 100 g of water was added to the system, a white water insolubilized product was formed. This water-insolubilized product was repeatedly washed with distilled water to obtain a celluloronic acid calcium salt.

The obtained calcium seuroronate salt was further suspended in 1 L of water and passed through a column filled with 100 mL of an ion exchange resin (Amberlite IR120 manufactured by Organo Corp.) for ion exchange treatment. The obtained aqueous solution of celouronic acid was lyophilized to obtain 11.8 g of white powder of celouronic acid sodium salt.

(Preparation of amylouronic acid)
1.0 g of water-soluble starch (manufactured by ACROS) was uniformly dispersed in distilled water at a concentration of 5%.
To this, an aqueous solution in which 19 mg of TEMPO and 0.25 g of sodium bromide were dissolved was added to prepare a solid content concentration of amylose of about 2 wt%. The reaction system was cooled and 3.0 g of 11% aqueous sodium hypochlorite solution was added to initiate the oxidation reaction.

The reaction temperature was always kept below 5 ° C.
During the reaction, the pH in the system decreases, but 0.5N-NaOH aqueous solution is sequentially added to adjust the pH to around 10.8, and 8.0 g of 11% sodium hypochlorite aqueous solution is further added according to the progress of the reaction. It was added dropwise while adjusting.

When approaching the amount of alkali added corresponding to 100% of the total number of moles of glucose residues, the rate of alkali addition becomes slow regardless of the dropping of the sodium hypochlorite aqueous solution, and the system is completely removed. Dissolved to a yellow uniform solution.

When the amount of alkali added reached 100% (12.34 ml) with respect to the total number of moles of glucose residues, ethanol was added to stop the reaction.
The reaction time was 2 hours.

When an aqueous solution in which 2.0 g of calcium chloride was previously dissolved in 10 g of water was added to the system, a white water insolubilized product was formed. This water-insolubilized product was repeatedly washed with distilled water to obtain calcium amylouronate.

The amylouronate calcium salt was suspended in 20 g of water, and 20 mL of an ion exchange resin (Amberlite IR120 manufactured by Organo Co., Ltd.) was added for ion exchange treatment. The ion exchange resin was removed from the aqueous amylouronate solution and lyophilized to obtain 1.2 g of sodium amylouronate salt as a white powder.

(Preparation of chitouronic acid)
10 g of chitin manufactured by Wako Pure Chemical Industries, Ltd. was immersed in 150 g of 45% aqueous sodium hydroxide solution and stirred at room temperature or lower for 2 hours. The periphery of the reaction vessel was cooled with ice water or the like, and 850 g of crushed ice was added with stirring. Chitin is almost dissolved by this alkali treatment. After neutralizing with hydrochloric acid and thoroughly washing with water, drying was not performed, and the obtained product was used as regenerated chitin as an oxidation raw material.

  A solution prepared by dissolving 0.08 g of TEMPO and 1.0 g of sodium bromide in 50 g of distilled water was added to 200 g of this regenerated chitin 2.5% suspension, and the mixture was cooled to 5 ° C. or lower. An 11% sodium hypochlorite aqueous solution (35 g) was added dropwise thereto to initiate the oxidation reaction. The reaction temperature was always kept below 5 ° C. During the reaction, the pH in the system was lowered, but a 0.5 N NaOH aqueous solution was sequentially added to adjust the pH to 10.75. Then, when the alkali addition amount corresponding to the mole number of 100% with respect to the total mole number of the primary hydroxyl group at the 6-position was reached, ethanol was added to stop the reaction.

When an aqueous solution in which 30 g of calcium chloride was previously dissolved in 200 g of water was added to the system, a white water insolubilized product was formed. This water-insolubilized product was repeatedly washed with distilled water to obtain calcium chitouronate. This was further suspended in 100 g of water, and passed through a column packed with 100 mL of an ion exchange resin (organo Corporation: Amberlite IR120) to perform an ion exchange treatment. This aqueous chitouronic acid solution was freeze-dried to obtain 11.5 g of a white powder of sodium chitouronic acid.

(Preparation of cellouronic acid)
As the regenerated cellulose, Benise manufactured by Asahi Kasei Kogyo Co., Ltd. is used. 10 g of regenerated cellulose is suspended in 500 g of distilled water. Until cooled.

To this, 104 g of an aqueous 11% sodium hypochlorite solution was added dropwise to initiate the oxidation reaction.

The reaction temperature was always kept below 5 ° C. During the reaction, the pH in the system was lowered, but 0.5N-NaOH aqueous solution was sequentially added to adjust the pH to 10.75. Then, when the alkali addition amount corresponding to the mole number of 100% with respect to the total mole number of the primary hydroxyl group at the 6-position was reached, ethanol was added to stop the reaction.

When an aqueous solution in which 20 g of calcium chloride was previously dissolved in 100 g of water was added to the system, a white water insolubilized product was formed. This water-insolubilized product was repeatedly washed with a water / ethanol mixed solution (volume ratio 50/50) to obtain calcium seuroronate.

The obtained calcium seuroronate salt was further suspended in 1 L of water and passed through a column filled with 100 mL of an ion exchange resin (Amberlite IR120 manufactured by Organo Corp.) for ion exchange treatment. The obtained aqueous solution of celouronic acid was lyophilized to obtain 11.8 g of white powder of celouronic acid sodium salt.

<Comparative Example 1>
1.0 g of water-soluble starch (manufactured by ACROS) was uniformly dispersed in distilled water at a concentration of 5%. To this, an aqueous solution in which 19 mg of TEMPO and 0.25 g of sodium bromide were dissolved was added to prepare a solid content concentration of amylose of about 2 wt%.

The reaction system was cooled and 3.0 g of 11% aqueous sodium hypochlorite solution was added to initiate the oxidation reaction. The reaction temperature was always kept below 5 ° C. During the reaction, the pH in the system decreases, but 0.5N-NaOH aqueous solution is sequentially added to adjust the pH to around 10.8, and 8.0 g of 11% sodium hypochlorite aqueous solution is further added according to the progress of the reaction. It was added dropwise while adjusting.

When approaching the amount of alkali added corresponding to 100% of the total number of moles of glucose residues, the rate of alkali addition becomes slow regardless of the dropping of the sodium hypochlorite aqueous solution, and the system is completely removed. Dissolved to a yellow uniform solution. When the amount of alkali added reached 100% (12.34 ml) with respect to the total number of moles of glucose residues, ethanol was added to stop the reaction. The reaction time was 2 hours.

The reaction solution was poured into an excess amount of ethanol to reprecipitate the product. Furthermore, after sufficiently washing with a solution of water: acetone = 1: 7, it was dehydrated with acetone and dried under reduced pressure at 40 ° C. to obtain 1.1 g of sodium salt of polyglucuronic acid as a white powder.

<Comparative example 2>
1.0 g of the same regenerated cellulose as the raw material of Example 3 was uniformly dispersed in distilled water at a concentration of 5%.
An aqueous solution in which 19 mg of TEMPO and 0.25 g of sodium bromide were dissolved was added thereto, and the solid content concentration of cellulose was adjusted to about 2 wt%.

The reaction system was cooled and 3.0 g of 11% aqueous sodium hypochlorite solution was added to initiate the oxidation reaction. The reaction temperature was always kept below 5 ° C.

During the reaction, the pH in the system decreases, but 0.5N-NaOH aqueous solution is sequentially added to adjust the pH to around 10.8, and 8.0 g of 11% sodium hypochlorite aqueous solution is further added according to the progress of the reaction. It was added dropwise while adjusting.

When approaching the amount of alkali added corresponding to 100% of the total number of moles of glucose residues, the rate of alkali addition becomes slow regardless of the dropping of the sodium hypochlorite aqueous solution, and the system is completely removed. Dissolved to a yellow uniform solution.

When the amount of alkali added reached 100% (12.34 ml) with respect to the total number of moles of glucose residues, ethanol was added to stop the reaction. The reaction time was 2 hours. The reaction solution was poured into an excess amount of ethanol to reprecipitate the product. Further, after sufficiently washing with a solution of water: acetone = 1: 7, it was dehydrated with acetone and dried under reduced pressure at 40 ° C. to obtain 1.1 g of white powdery sodium cellulonate.

<Comparative Example 3>
As in Example 1, Daiichi Seika Kogyo Co., Ltd. Daikitosan 100D (VL) was used as 100% deacetylated chitosan. 10 g of this chitosan was dissolved in 190 g of 10% acetic acid and diluted with 1 L of methanol. When 12.68 g of acetic anhydride was added with stirring, gelation occurred in a few minutes. After standing for 15 hours, 1 L of methanol was further added and stirred with a homogenizer, and 2N-NaOH aqueous solution was added to neutralize to pH 7. This was filtered, washed thoroughly with methanol and deionized water, and then frozen. It was dried to obtain 11.6 g of N-acetylated chitosan. The degree of N-acetylation by elemental analysis was 95%.

1.0 g of the adjusted N-acetylated chitosan was uniformly dispersed in distilled water at a concentration of 5%. An aqueous solution in which 19 mg of TEMPO and 0.25 g of sodium bromide were dissolved was added to prepare a chitin solid content concentration of about 2 wt%. The reaction system was cooled and 3.0 g of 11% aqueous sodium hypochlorite solution was added to initiate the oxidation reaction. The reaction temperature was always kept below 5 ° C.

During the reaction, the pH in the system decreases, but 0.5N-NaOH aqueous solution is sequentially added to adjust the pH to around 10.8, and 8.0 g of 11% sodium hypochlorite aqueous solution is further added according to the progress of the reaction. It was added dropwise while adjusting. When approaching the amount of alkali added corresponding to 100% of the total number of moles of glucose residues, the rate of alkali addition becomes slow regardless of the dropping of the sodium hypochlorite aqueous solution, and the system is completely removed. Dissolved to a yellow uniform solution.

When the amount of alkali added reached 100% with respect to the total number of moles of glucose residues, ethanol was added to stop the reaction. The reaction time was 2 hours. The reaction solution was poured into an excess amount of ethanol to reprecipitate the product. Further, after sufficiently washing with a solution of water: acetone = 1: 7, it was dehydrated with acetone and dried under reduced pressure at 40 ° C. to obtain 1.1 g of white powdery sodium chitouronic acid salt.

In the conventional production method (comparative example), polyuronic acid is dissolved in water, so that washing with a solvent containing a large amount of water is difficult, and a large amount of organic solvent is used. On the other hand, by using the production method of the present invention, it is possible to wash with an aqueous solvent in the step of isolation and purification, and finally it is possible to obtain the same water-soluble polyuronic acid. Furthermore, by using the production method of the present invention, it became possible to obtain water-soluble polyuronic acid with a very high yield.

According to the present invention, it becomes possible to produce polyuronic acid by washing with an aqueous solvent, the safety of the product is increased, and these polyuronic acids are easily biodegraded, and high yields of highly soluble polyuronic acid are obtained. Therefore, it can be used as medical materials, chemicals, foods, hygiene products, cosmetics, etc. in addition to its use as industrial general-purpose applications.

Claims (10)

At least a step of selectively oxidizing a polysaccharide, a step of adding a polyvalent cation to the oxidized polysaccharide to produce a water-insolubilized product, a step of washing the water-insolubilized product with an aqueous solvent, and the water A method for producing a water-soluble polyuronic acid represented by any one of chemical formulas (1) to (3), comprising a step of ion-exchange of an insolubilized product.

2. The method for producing water-soluble polyuronic acid according to claim 1, wherein in the oxidation step, the polysaccharide is dispersed or dissolved in an aqueous system and oxidized using a co-oxidant in the presence of an N-oxyl compound. . The method for producing water-soluble polyuronic acid according to any one of claims 1 to 2, wherein the polyvalent cation is a metal salt. The method for producing water-soluble polyuronic acid according to claim 3, wherein the polyvalent cation is an alkaline earth metal salt. The method for producing a water-soluble polyuronic acid according to claim 4, wherein the alkaline earth metal salt is a calcium salt. The method for producing water-soluble polyuronic acid according to any one of claims 1 to 2, wherein the polyvalent cation is a polyamine. The water-soluble polyuronic acid according to any one of claims 1 to 6, wherein the polysaccharide is one kind selected from starch, cellulose, chitin, chitosan, and pullulan, or a mixture of two or more kinds. Production method. The method for producing water-soluble polyuronic acid according to any one of claims 1 to 7, wherein the aqueous solvent is water or a solvent mainly composed of water. 9. The ion exchange step according to any one of claims 1 to 8, wherein the polyuronic acid polyvalent cation salt suspension is passed through an ion exchange resin for ion exchange and water-solubilized again. A method for producing water-soluble polyuronic acid. A water-soluble polyuronic acid produced by the production method according to any one of claims 1 to 9.