JP2006124598A - Method for producing water-soluble polyuronic acid - Google Patents

Abstract

PROBLEM TO BE SOLVED: To solve the problem inherent in the present invention by utilizing the original advantage of polysaccharides that have less adverse effects on the environment and the human body, while making polyuronic acid and its aqueous solution imparted hydrophilicity to polysaccharides without using an organic solvent in an aqueous system. The object is to provide a method of manufacturing.
[MEANS FOR SOLVING PROBLEMS] The present invention comprises at least a step of selectively oxidizing a polysaccharide, a step of adding a polyvalent cation to the oxidized polysaccharide to cause precipitation, washing with water, and a desalting step. A feature of the present invention is to provide a method for producing water-soluble polyuronic acid. The present invention also provides a method for producing water-soluble polyuronic acid, wherein the polyvalent cation is a metal salt. The present invention also provides a method for producing water-soluble polyuronic acid, wherein the polyvalent cation is a polyamine.
[Selection figure] None

Description

  The present invention relates to a simple production method that does not use an organic solvent of polyuronic acid having a uniform structure derived from a polysaccharide.

  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 this N-oxyl compound as a catalyst proceeds during an aqueous reaction by using a catalyst such as sodium bromide in addition to an N-oxyl compound such as TEMPO. As the carboxyl group or its sodium salt increases with the progress of oxidation, not only water-soluble polysaccharides such as starch but also poorly soluble polysaccharides such as cellulose and chitin are given 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 2002-360524 A

  Accordingly, an object of the present invention is to produce a polyuronic acid or an aqueous solution thereof, which is hydrophilic to a polysaccharide without using an organic solvent, while taking advantage of the inherent advantage of the polysaccharide that there is little adverse effect on the environment and the human body. A method is provided.

  The invention according to claim 1 comprises at least a step of selectively oxidizing a polysaccharide, a step of adding a polyvalent cation to the oxidized polysaccharide to cause precipitation, washing with water, and a desalting step. Is a method for producing a water-soluble polyuronic acid represented by any one of chemical formulas (1) to (3).

  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. It is a manufacturing method of water-soluble polyuronic acid.

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

  The invention according to claim 7 is characterized in that the polysaccharide is one kind selected from starch, cellulose, chitin, chitosan and pullulan, or a mixture of two or more kinds. It is a manufacturing method of water-soluble polyuronic acid of description.

  The invention according to claim 8 is characterized in that in the desalting step, the suspension of polyuronic acid polyvalent cation salt is passed through an ion exchange resin for desalting. It is a manufacturing method of water-soluble polyuronic acid.

  The invention according to claim 9 is a water-soluble polyuronic acid produced by the production method according to any one of claims 1 to 8.

  According to the production method of the present invention, it is possible to produce a polyuronic acid imparted with hydrophilicity derived from a natural polysaccharide having a uronic acid structure with a controlled chemical structure in an aqueous system without using an organic solvent. Further, by not using an organic solvent, the safety of the product is increased, and these polyuronic acids are easily biodegraded, have high biocompatibility, and can further inhibit subsequent modification and other treatments. Since polyuronic acid with a small amount of metal ions such as sodium is produced, it can be used as a medical material, medicine, food, sanitary goods, cosmetics, etc. in addition to its industrial use.

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, or 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 cellulose regeneration treatment, 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 co-oxidant, a target oxidation reaction such as halogen, hypohalous acid, halohalic 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 to use TEMPO as the N-oxyl compound and perform the oxidation reaction using sodium hypochlorite as a co-oxidant 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 more preferable. 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 will be referred to as amilouronic 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, the process of precipitating 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, that is, insolubilizes in water. Examples include various metal salts including alkaline earth metal salts such as aluminum, silica, titanium, vanadium, manganese, iron, cobalt, nickel, copper, zinc, silver, barium, and organic polyvalent cations such as polyamines. , And can be freely selected according to the use and necessary 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 of precipitating 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 added to the aqueous solution system containing polyuronic acid. .
For example, when a calcium salt is used as the polyvalent cation, polyuronic acid existing as a sodium salt is precipitated by insulatively replacing sodium with calcium and insolubilizing. This exchange reaction occurs relatively quickly.

  Furthermore, before the step of generating the precipitate, a step of filtering the reaction solution to remove impurities such as undissolved substances that are insufficiently reacted may be performed.

  Next, the polyuronic acid polyvalent cation salt that is the precipitate is sufficiently washed with water. Since the precipitate of the polyuronic acid polyvalent cation salt of the present invention has a structure in which the carboxyl group of the polymer is crosslinked via a cation, there is little loss due to outflow when washing with ion-exchanged water or distilled water, Cleaning can be easily performed by decantation or filtration. At the time of washing, reagents used in the oxidation reaction, generated salts, excess calcium salts, and the like can be removed.

  Here, the isolated calcium salt of polyuronic acid has a stable structure and can be stored in a dry powder state. Various methods such as air drying, heat drying, and freeze drying can be used for drying.

  Next, the desalting process will be described. The polyuronic acid polyvalent cation salt obtained by the oxidation method and the washing step as described above, for example, calcium salt (COOCa type) is dispersed in water, treated with acid, reprecipitated with ethanol, washed and dried. Alternatively, COOH-type desalted polyuronic acid can be obtained by removing impurities by dialysis. The desalted polyglucuronic acid can also be obtained by treating the aqueous dispersion with an ion exchange resin. Considering that all treatments are carried out in an aqueous system, this method using an ion exchange resin is more preferable, and those that can separate the ion exchange resin from the treated aqueous solution and have a low ion content can be directly used as an aqueous polyuronic acid solution. It is also possible to do. Moreover, the dried polyuronic acid can be obtained by freeze-drying this aqueous solution.

Furthermore, the polyuronic acid obtained by the production method of the present invention has a highly reactive carboxyl group as compared with a hydroxyl group or the like. In the reaction of the carboxyl group, it is preferable from the viewpoint of reaction efficiency that the carboxyl group forms a COOH type rather than a salt. Even if the polyuronic acid that can be obtained by the production method of the present invention is of the COOH type, it exhibits high water solubility, and is therefore very effective as a reaction material for secondary modification.
In particular, the chitouronic acid and amylouronic acid described above are water-soluble even in the COOH type, and are highly water-soluble in a wide pH range of pH 1-14.

  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.

  First, production examples of N-acetylated chitosan as a raw material used in Examples and Comparative Examples will be described.

<Production Example 1>
(Preparation of N-acetylated chitosan)
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 leaving this 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%.

(Preparation of chitouronic acid)
10 g of N-acetylated chitosan prepared in Production Example 1 was suspended in 400 g of distilled water, and a solution prepared by dissolving 0.1 g of TEMPO and 2.0 g of sodium bromide was added to 100 g of distilled water 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 11 g of calcium chloride was previously dissolved in 100 g of water was added to the system, a white precipitate was formed. This precipitate was repeatedly washed with distilled water to obtain calcium chitouronic acid. The obtained calcium chitouronic acid salt was further suspended in 100 g of water, and passed through a column filled with 70 mL of an ion exchange resin (Amberlite IR120 manufactured by Organo Corp.) regenerated into H-type for desalting treatment. . The obtained chitouronic acid aqueous solution was freeze-dried to obtain 8.7 g of white powder of chitouronic acid.

(Preparation of amylouronic acid)
10 g of starch was dissolved by heating in 400 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 precipitate was formed. This precipitate was washed repeatedly 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 70 mL of an ion exchange resin (Amberlite IR120 manufactured by Organo Corp.) regenerated to H type for desalting treatment. The obtained aqueous solution of amyloulonic acid was freeze-dried to obtain 8.7 g of white powdered amyloulonic acid.

(Preparation of cellouronic acid)
As the regenerated cellulose, Benise manufactured by Asahi Kasei Kogyo Co., Ltd. was used. 10 g of regenerated cellulose was suspended in 400 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 11 g of calcium chloride was previously dissolved in 100 g of water was added to the system, a white precipitate was formed. This precipitate 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 70 mL of an ion exchange resin (Amberlite IR120 manufactured by Organo Corp.) regenerated into H-type for desalting treatment. . The obtained aqueous solution of celouronic acid was lyophilized to obtain 9.8 g of cerouronic acid as a white powder.

  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 added successively 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 1.1 g of calcium chloride was previously dissolved in 10 g of water was added to the system, a white precipitate was formed. This precipitate was washed repeatedly with distilled water to obtain calcium amylouronate. Desalting treatment was performed by adding 70 mL of ion-exchange resin (Amberlite IR120 manufactured by Organo Corp.) regenerated into H-type by suspending calcium amylouronate in 100 g of water. The ion exchange resin was removed from the aqueous solution of amyloulonic acid and freeze-dried to obtain 8.7 g of white powdered amyloulonic acid.

<Comparative example>
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 added successively 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 1.2 g of sodium salt of polyglucuronic acid in the form of white powder. 1.0 g of the resulting polyglucuronic acid sodium salt was dissolved in 40 ml of distilled water, and 2N hydrochloric acid was added to pH 1 while stirring. The solution remained a clear solution. This 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, dehydration with acetone and drying under reduced pressure at 40 ° C., 0.8 g of desalted amylouronic acid in the form of a white powder was obtained.

  In the comparative example, which is a conventional production method, a large amount of organic solvent is used, but by using the production method of the present invention, water-soluble polyuronic acid can be obtained without using an organic solvent in the isolation and purification process. Is possible. Furthermore, as is clear when Example 4 is compared with Comparative Examples, it is possible to obtain water-soluble polyuronic acid in a very high yield by using the production method of the present invention.

  According to the present invention, polyuronic acid can be produced without using an organic solvent, the safety of the product is increased, and these polyuronic acids are easily biodegraded and have high biocompatibility. As polyuronic acid with low metal ions such as sodium is generated, which can inhibit treatment such as reforming, it can be used as a general-purpose industrial application, as well as medical materials, chemicals, foods, hygiene products, cosmetics, etc. It is possible to use.

Claims (9)

The chemical formula (1) is characterized by comprising at least a step of selectively oxidizing a polysaccharide, a step of adding a polyvalent cation to the oxidized polysaccharide to cause precipitation, washing with water, and a desalting step. To a method for producing a water-soluble polyuronic acid represented by any one of (3).

  2. The method for producing water-soluble polyuronic acid according to claim 1, wherein the oxidizing step comprises dispersing or dissolving the polysaccharide in an aqueous system and oxidizing the polysaccharide using a co-oxidant in the presence of an N-oxyl compound.   The method for producing water-soluble polyuronic acid according to claim 1, wherein the polyvalent cation is a metal salt.   The method for producing a water-soluble polyuronic acid according to any one of claims 1 to 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 claim 1, wherein the polyvalent cation is a polyamine.   The method for producing a 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. .   The method for producing water-soluble polyuronic acid according to any one of claims 1 to 7, wherein the desalting step includes desalting a suspension of polyuronic acid polyvalent cation salt through an ion exchange resin.   A water-soluble polyuronic acid produced by the production method according to any one of claims 1 to 8.