JP6077424B2 - Method for producing water-insoluble molded body and water-insoluble molded body - Google Patents

Description

  The present invention relates to a water-insoluble molded article and a production method thereof, and an adhesion preventing material and a production method thereof.

  Polyanionic polysaccharides such as hyaluronic acid and alginic acid are known to exhibit moderate viscosity, adhesiveness, moisture retention, and biocompatibility. For this reason, these polyanionic polysaccharides and salts thereof are widely used as raw materials for medical materials, food materials, cosmetic materials and the like.

  Among these, hyaluronic acid is excellent in dispersibility and water retention, and has high safety and biocompatibility, and thus is used in various applications such as foods, cosmetics, and pharmaceuticals. For example, in the medical field, hyaluronic acid is used as a raw material for joint lubricants and anti-adhesion materials. However, since sodium hyaluronate used as a raw material has high water solubility, it is necessary to perform some insolubilization treatment when used for the above-mentioned purposes.

  Until now, various methods for insolubilizing sodium hyaluronate by a crosslinking reaction utilizing a carboxy group have been studied. For example, Patent Document 1 describes a method for producing a water-insoluble derivative of a polyanionic polysaccharide such as hyaluronic acid or carboxymethylcellulose by a crosslinking reaction using carbodiimide.

  Patent Document 2 describes a method of water-insolubilizing polyanionic polysaccharides such as hyaluronic acid and carboxyalkyl cellulose by ion bonding using a polyvalent cation. Furthermore, Patent Documents 3 and 4 describe a method for making carboxymethyl cellulose hardly soluble in water using a strong acid such as hydrochloric acid, nitric acid, or sulfuric acid.

  Patent Document 5 describes a method for producing a water-insoluble film by bringing carboxymethyl cellulose into contact with a metal salt and performing ion exchange. Patent Document 6 describes a method in which a sodium hyaluronate aqueous solution is cooled to −20 ° C. under acidic conditions to form intramolecular crosslinks and thereby insolubilize in water.

Special table 2003-518167 gazette JP-A-5-124968 International Publication No. 01/034214 JP 2004-051531 A JP-A-6-128395 JP 2003-252905 A

  However, since the method described in Patent Document 1 uses a cross-linking agent, it is often difficult to apply when considering the safety of uses such as pharmaceuticals that are imparted to the human body. Patent Documents 2 and 5 do not describe any degree of water insolubility of the obtained film or the like. Furthermore, the poorly water-soluble material produced by the methods described in Patent Documents 3 and 4 is not necessarily sufficient as a method for insolubilizing carboxymethylcellulose because 50% or more of the material dissolves in water in 10 to 30 hours. I couldn't say that.

  Patent Document 5 describes the breaking stress and breaking elongation of the obtained film and the like, but does not describe any degree of water insolubility. Further, in the method described in Patent Document 6, it is necessary to adjust the pH of the sodium hyaluronate aqueous solution to about 1.2, and the viscosity is remarkably increased, so that handling such as molding is difficult. There is also a problem in terms of power cost required for cooling.

  The present invention has been made in view of such problems of the prior art, and the problem is that the original characteristics of the polyanionic polysaccharide as a raw material are maintained and the safety is high. Another object of the present invention is to provide a method for easily producing a water-insoluble molded article useful as a medical material, a food material, a cosmetic material, or the like. Moreover, the place made into the subject of this invention is providing the water-insoluble molded object manufactured by said method, the adhesion preventing material, and its manufacturing method.

  As a result of diligent studies to achieve the above-mentioned problems, the present inventors contact a raw material molded body formed using a water-soluble salt of a polyanionic polysaccharide with at least one of an organic acid and an organic acid anhydride vapor. As a result, the present inventors have found that the above-described problems can be achieved, and have completed the present invention.

That is, according to the present invention, the following method for producing a water-insoluble molded article is provided.
[1] A raw material molded body formed using a water-soluble salt of a polyanionic polysaccharide is brought into contact with the vapor of at least one of an organic acid and an organic acid anhydride to insolubilize the raw material molded body to be water-insoluble. A method for producing a water-insoluble molded article comprising a step of forming a molded article.
[2] The polyanionic polysaccharide according to [1], wherein the polyanionic polysaccharide is at least one selected from the group consisting of carboxyalkyl cellulose, carboxymethyl starch, chondroitin sulfate, hyaluronic acid, heparin, alginic acid, pectin, and carrageenan. A method for producing a water-insoluble molded article.
[3] The water according to [1] or [2], wherein the organic acid is at least one of acetic acid and propionic acid, and the organic acid anhydride is at least one of acetic anhydride and propionic anhydride. A method for producing an insoluble molded article.
[4] The water-insoluble molded product according to any one of the above [1] to [3], wherein the shape of the raw material molded product is powder, particle, film, lump, fiber, tubular, or sponge. Manufacturing method.

Moreover, according to this invention, the water-insoluble molded object shown below is provided.
[5] A water-insoluble molded product produced by the production method according to any one of [1] to [4].
[6] The water-insoluble molded article according to [5], which is powdery, particulate, film-like, massive, fibrous, tubular, or sponge-like.
[7] The water-insoluble molded product according to [5] or [6], which is a medical material, a food material, or a cosmetic material.

Furthermore, according to this invention, the manufacturing method of the adhesion prevention material shown below is provided.
[8] A method for producing an adhesion-preventing material, comprising a step of holding a polyhydric alcohol or a polyhydric alcohol aqueous solution in the water-insoluble molded product according to [5] or [6].

Moreover, according to this invention, the adhesion prevention material shown below is provided.
[9] An adhesion preventing material produced by the production method according to [8].

  According to the method for producing a water-insoluble molded article of the present invention, the original characteristics of the polyanionic polysaccharide as a raw material are maintained, and the safety is high, as a medical material, a food material, a cosmetic material, and the like. A useful water-insoluble molded product can be easily produced.

  Embodiments of the present invention will be described below, but the present invention is not limited to the following embodiments.

(Water-insoluble molded product and method for producing the same)
The method for producing a water-insoluble molded product according to the present invention comprises bringing a raw material molded product formed using a water-soluble salt of a polyanionic polysaccharide into contact with a vapor of at least one of an organic acid and an organic acid anhydride, thereby forming the raw material. A step (water insolubilization step) of forming a water-insoluble molded body by insolubilizing the body with water. The details will be described below.

  The raw material molded body used in the water insolubilization step is formed using a water-soluble salt of a polyanionic polysaccharide. The polyanionic polysaccharide is a polysaccharide having one or more negatively charged anionic groups such as a carboxy group and a sulfonic acid group in its molecular structure. The water-soluble salt of the polyanionic polysaccharide is a salt in which at least a part of the anionic group in the polyanionic polysaccharide forms a salt. The anionic group in the polyanionic polysaccharide may be introduced into the polysaccharide molecule.

  Specific examples of the polyanionic polysaccharide include carboxyalkyl cellulose such as carboxymethyl cellulose and carboxyethyl cellulose, carboxymethyl starch, carboxymethyl amylose, chondroitin sulfate (including chondroitin-4-sulfate and chondroitin-6-sulfate), hyaluronic acid, Examples include heparin, heparin sulfate, heparan sulfate, alginic acid, pectin, carrageenan, dermatan sulfate, and dermatan-6-sulfate. Of these, carboxymethylcellulose, carboxymethyl starch, chondroitin sulfate, hyaluronic acid, heparin, alginic acid, pectin, and carrageenan are preferable, and carboxymethylcellulose, hyaluronic acid, and alginic acid are more preferable. These polyanionic polysaccharides can be used singly or in combination of two or more.

  Examples of water-soluble salts of polyanionic polysaccharides include inorganic salts, ammonium salts, and organic amine salts. Specific examples of the inorganic salt include alkali metal salts such as sodium and potassium; alkaline earth metal salts such as calcium salts; metal salts such as zinc and iron.

  The water-soluble salt of the polyanionic polysaccharide is not particularly limited as long as it has physical properties such as being able to form a raw material molded body having a desired shape. Specifically, when the molecular weight of the water-soluble salt of polyanionic polysaccharide (for example, sodium carboxymethylcellulose and sodium hyaluronate) is preferably 5 to 2 million, more preferably 200 to 1.5 million, the strength is higher. A raw material molded body and a water-insoluble molded body can be produced.

  The raw material molded body can be obtained, for example, by forming an aqueous solution obtained by dissolving a water-soluble salt of a polyanionic polysaccharide in water into a desired shape and then drying the solution. Examples of the shape of the raw material molded body include powder, particle, film, lump, fiber, tubular, and sponge. By insolubilizing the raw material molded body of these shapes, a water-insoluble molded body having a shape corresponding to the use such as powder, particle, film, lump, fiber, tube, and sponge can be obtained. . If necessary, the obtained water-insoluble molded product may be further molded and processed into a desired shape.

  The steam brought into contact with the raw material molded body contains at least one of an organic acid and an organic acid anhydride. Specific examples of the organic acid include carboxylic acids such as acetic acid and propionic acid. Specific examples of the organic acid anhydride include carboxylic acid anhydrides such as acetic anhydride and propionic anhydride. These organic acids and organic acid anhydrides can be used singly or in combination of two or more. In addition, when an organic acid anhydride is used as a vapor source, the organic acid generated by hydrolysis of the organic acid anhydride or the like is usually contained in the vapor together with the organic acid anhydride. The organic acid or organic acid anhydride may be used as it is, but may be used by dissolving or dispersing in a solvent. It is also possible to promote the generation (vaporization) of steam by heating in an appropriate temperature range.

  In the water insolubilization step, the raw material molded body is brought into contact with at least one of an organic acid and an organic acid anhydride (hereinafter also simply referred to as “steam”). By bringing the raw material molded body into contact with the above, the raw material molded body is insolubilized and a water-insoluble molded body is formed. The method of bringing the raw material compact into contact with the steam is not particularly limited, but it is preferable that the steam is brought into contact with the entire raw material compact for an appropriate time. Specifically, a method in which both are brought into contact in a closed container is preferable. The amount of the organic acid or the like to be used is not particularly limited, but it is preferable to supply a sufficient amount of the organic acid or the like to maintain the gas-liquid equilibrium state until the water insolubilization treatment is completed.

  The temperature during the treatment may be usually 0 to 100 ° C. However, the temperature during the treatment is preferably 15 to 40 ° C. from the viewpoint of suppressing the degradation and modification of the polyanionic polysaccharide and from the viewpoint of appropriately controlling the amount of vapor generated and vapor volatilization. After the water insolubilization step, the water-insoluble molded product of the present invention can be obtained by washing with water or a water-soluble organic solvent as necessary.

  The reaction mechanism (reaction formula) assumed when a raw material molded body formed using a sodium salt of a polyanionic polysaccharide is brought into contact with vapor of acetic acid and subjected to water insolubilization treatment is shown below. However, this invention is not limited at all by the following reaction mechanism assumed.

In reaction formula (1), R ₁ represents the main chain of the polyanionic polysaccharide. Acetic acid (steam) deprives sodium of the polyanionic polysaccharide in contact. For this reason, it is presumed that the carboxy group is changed from a sodium salt type to an acid type to produce a water-insoluble (poorly water-soluble) polyanionic polysaccharide, and sodium acetate is by-produced. In addition, about the reaction mechanism of a water insolubilization process, the case where it is progressing through the water | moisture content in atmosphere or a raw material molded object other than the case shown by the said Reaction formula (1) is also assumed, for example.

  Note that not all anionic groups in the molecule of the polyanionic polysaccharide need to be in the acid form. That is, it is only necessary that the amount of anionic group in which the obtained water-insoluble molded product is sufficiently water-insoluble is in an acid form.

  For example, even when a raw material molded body formed using a water-soluble salt of a polyanionic polysaccharide is immersed in an inorganic acid such as hydrochloric acid or an organic acid such as acetic acid, a sufficiently water-insoluble molded body can be obtained. It is extremely difficult. This is thought to be because inorganic acids and organic acids are less likely to penetrate into the raw material molded body, and only the anionic group of the polyanionic polysaccharide constituting the surface layer of the raw material molded body remains in the acid form. It is done. Further, even when the raw material molded body is brought into contact with vapor of an inorganic acid (strong acid) such as hydrochloric acid, it is extremely difficult to obtain a molded body sufficiently insolubilized in water. This is considered to be because the polyanionic polysaccharide forming the raw material molded body is decomposed by the vapor of the strong acid, and the shape of the molded body cannot be maintained and collapses.

  On the other hand, in the method for producing a water-insoluble molded article of the present invention, at least one of an organic acid and an organic acid anhydride is used. For this reason, the vapor penetrates to the inside of the raw material molded body, and not only the surface layer but also the anionic group of the polyanionic polysaccharide located inside can be changed to the acid type to obtain a sufficiently water-insoluble molded body. It is considered possible.

  The water-insoluble molded product of the present invention produced by the above procedure exhibits sufficient water-insolubility. In addition, since it is not necessary to use a crosslinking agent in the method for producing a water-insoluble molded article of the present invention, a structure such as a functional group derived from the crosslinking agent may be incorporated into the molecules constituting the obtained water-insoluble molded article. Absent. For this reason, the water-insoluble molded article of the present invention produced by the above production method retains the original characteristics of the polyanionic polysaccharide as a raw material, is easy to handle, and is safe for living organisms. high. Furthermore, since it also has degradability in vivo, the water-insoluble molded product of the present invention is not only a food material or a cosmetic material, but also an anti-adhesion material, a wound dressing material, a drug sustained-release base material, and pressure ulcer prevention. It is suitable as a medical material such as a material.

  In the present specification, “water-insoluble” means a property that does not easily dissolve in water. More specifically, when immersed in water or physiological saline at room temperature (25 ° C.), preferably after 24 hours, more preferably after 72 hours, particularly preferably after 2 weeks. However, what is visually recognizable as maintaining the original shape is said to be “water-insoluble”.

(Anti-adhesion material and its manufacturing method)
Next, the manufacturing method of the adhesion prevention material of this invention is demonstrated. The method for producing an antiadhesive material of the present invention includes a step of holding a polyhydric alcohol or a polyhydric alcohol aqueous solution in the water-insoluble molded article. Specific examples of the polyhydric alcohol include ethylene glycol, diethylene glycol, polyethylene glycol, methylglycerol, polyoxyelene glycoside, maltitol, mannitol, xylitol, sorbitol, reduced starch syrup, dipropylene glycol, butylene glycol, propylene glycol, glycerin ( Glycerol), polyglycerol, glycerol fatty acid ester and the like. Of these, polyhydric alcohols used in the medical field and food field such as glycerin, xylitol, sorbitol, and low molecular weight polyethylene glycol are preferably used. These suitably used polyhydric alcohols can be obtained from the market and used as they are. As for glycerin, sorbitol, etc., it is desirable to use those suitable for the Japanese Pharmacopoeia. Glycerin is particularly preferable because it is a material that is safe enough to be used as an intravenous injection.

  Examples of the method for retaining the polyhydric alcohol or the polyhydric alcohol aqueous solution in the water-insoluble molded body include a method of immersing the water-insoluble molded body in the polyhydric alcohol or a polyhydric alcohol aqueous solution having a predetermined concentration. That is, by immersing a water-insoluble molded article having a predetermined shape in a polyhydric alcohol aqueous solution and replacing the interior of the water-insoluble molded article with the polyhydric alcohol aqueous solution, the polyhydric alcohol aqueous solution having a desired concentration is retained, The adhesion preventing material of the present invention can be obtained.

  EXAMPLES Hereinafter, although this invention is demonstrated concretely based on an Example, this invention is not limited to these Examples. In the examples and comparative examples, “parts” and “%” are based on mass unless otherwise specified.

Example 1
1.0 g of sodium hyaluronate (molecular weight (nominal value): 800,000, manufactured by Kikkoman Biochemifa) and 99.0 g of water were mixed and stirred in a beaker to obtain a uniform aqueous solution. The obtained aqueous solution was poured into a stainless steel vat and dried at 30 ° C. to obtain a sodium hyaluronate film. The petri dish containing the obtained sodium hyaluronate film and 10 mL of acetic acid as a vapor source was placed in a glass desiccator, and left for 5 days at room temperature (25 ° C.) for water insolubilization treatment. In addition, it was observed that one day after being left standing, it was partially insolubilized and water-insoluble fragments were formed. The water-insoluble membrane was washed with methanol, 80% aqueous methanol, and water in this order to obtain a water-insoluble membrane. When the “solubility test” shown below was carried out using the obtained water-insoluble membrane, the original shape of the membrane was retained for 72 hours or more.

(Evaluation 1: Solubility test)
The water-insoluble membrane cut into 2 cm square was placed in a container having a diameter of 3.5 cm and a depth of 1.5 cm, and 5 mL of PBS buffer (pH 6.8) was added. This container was put into a shaker adjusted to 37 ° C. and shaken at 10 to 20 rpm. The state change of the water-insoluble membrane over time was visually observed.

(Comparative Example 1)
A sodium hyaluronate film (not water-insolubilized) produced by the same procedure as in Example 1 was used as Comparative Example 1. When the above-mentioned “solubility test” was carried out using this sodium hyaluronate membrane, the membrane quickly dissolved.

(Comparative Example 2)
Except that hydrochloric acid was used as the vapor source and the standing (contact) time was 3 days, when the water insolubilization treatment was performed in the same manner as in Example 1 described above, the membrane could be taken out in a rag. There wasn't.

(Example 2)
A water-insoluble membrane was obtained in the same manner as in Example 1 except that acetic anhydride was used as the vapor source and the standing (contact) time was 13 days. When the above-mentioned “solubility test” was performed using the obtained water-insoluble membrane, the original shape of the membrane was maintained for 72 hours or more.

(Example 3)
A water-insoluble film was obtained in the same manner as in Example 1 except that propionic anhydride was used as the vapor source and the standing (contact) time was 10 days. When the above-mentioned “solubility test” was performed using the obtained water-insoluble membrane, the original shape of the membrane was maintained for 72 hours or more.

Example 4
Instead of sodium hyaluronate, sodium carboxymethylcellulose (trade name “Serogen PR-S”, manufactured by Daiichi Kogyo Seiyaku Co., Ltd., 2% viscosity: 25 to 35 mPa · s) was used, and the standing (contact) time was 1 day. A water-insoluble membrane was obtained in the same manner as in Example 1 except that. When the above-mentioned “solubility test” was performed using the obtained water-insoluble membrane, the original shape of the membrane was maintained for 72 hours or more.

(Example 5)
A water-insoluble membrane was obtained in the same manner as in Example 4 except that acetic anhydride was used as the vapor source and the standing (contact) time was 10 days. When the above-mentioned “solubility test” was performed using the obtained water-insoluble membrane, the original shape of the membrane was maintained for 72 hours or more.

(Example 6)
A water-insoluble film was obtained in the same manner as in Example 4 except that propionic acid was used as the vapor source and the standing (contact) time was 10 days. When the above-mentioned “solubility test” was performed using the obtained water-insoluble membrane, the original shape of the membrane was maintained for 72 hours or more.

(Example 7)
A water-insoluble membrane was obtained in the same manner as in Example 1 except that sodium alginate (manufactured by Wako Pure Chemical Industries, 1% viscosity: 500 to 600 mPa · s) was used instead of sodium hyaluronate. When the above-mentioned “solubility test” was performed using the obtained water-insoluble membrane, the original shape of the membrane was maintained for 72 hours or more.

(Example 8)
1.0 g of sodium hyaluronate (molecular weight (nominal value): 800,000, manufactured by Kikkoman Biochemifa) and 99.0 g of water were mixed and stirred in a beaker to obtain a uniform aqueous solution. The obtained aqueous solution was poured into a stainless steel vat, frozen at −30 ° C., and freeze-dried at a shelf heating temperature of 120 ° C. to obtain a sponge-like molded body made of sodium hyaluronate. The obtained sponge-like molded product and a petri dish containing 10 mL of acetic acid as a vapor source were placed in a glass desiccator and left at room temperature (25 ° C.) for 5 days for water insolubilization treatment. The water-insolubilized molded body was washed with methanol, 80% aqueous methanol solution and water in this order to obtain a water-insoluble sponge-like molded body. When the above-mentioned “solubility test” was performed on the obtained water-insoluble sponge-like molded product, the sponge-like original shape was retained for 72 hours or more.

Example 9
10 g of sodium hyaluronate (molecular weight (nominal value): 800,000, manufactured by Kikkoman Biochemifa Co., Ltd.) was dissolved in 90 g of water to obtain a uniform and viscous aqueous sodium hyaluronate solution. The obtained sodium hyaluronate aqueous solution was put into a syringe equipped with an 18 gauge needle and extruded to obtain a fibrous shaped body. Since the obtained fibrous shaped product had a high viscosity, it was held in a fibrous form. The obtained fibrous shaped product and a petri dish containing 10 mL of acetic acid as a steam source were placed in a glass desiccator and left at room temperature (25 ° C.) for 5 days for water insolubilization treatment. The water-insolubilized molded body was washed with methanol, 80% aqueous methanol solution, and water in this order to obtain a water-insoluble fibrous molded body. When the above-described “solubility test” was performed on the obtained water-insoluble fibrous shaped article, the fibrous original shape was retained for 72 hours or more.

(Example 10)
The water-insoluble sponge-like molded product produced in Example 8 was cut into a bowl shape and then impregnated with a commercial lotion. The saddle-shaped sponge-like molded body did not dissolve in the skin lotion. Moreover, since the sticking property to skin was high, it could be used as a cosmetic material for sticking to the eyes.

(Example 11)
The water-insoluble membrane produced in Example 1 cut into a size of 12 cm × 9 cm was immersed in a 10% glycerin aqueous solution, then air-dried and sealed in a sterilization bag. The anti-adhesion membrane was obtained by sterilizing the entire sterilization bag with irradiation of 25 kGy. An adult dog (beagle dog, female, 1.5 years old, weight about 10 kg) was opened after general anesthesia treatment, and the epidermis epidermis was peeled into 3 cm square. The abdomen was closed by placing an adhesion-preventing membrane so as to cover the peeled portion. Two weeks later, the dog was opened after general anesthesia, and no adhesions occurred. In addition, the anti-adhesion membrane placed (implanted) in the dog's body disappeared two weeks after implantation. This is presumed that the carboxy group of hyaluronic acid constituting the anti-adhesion membrane was gradually neutralized by sodium ions etc. in the living body, and changed into soluble hyaluronate, dissolved and absorbed into the living body. The On the other hand, it was observed that adhesion occurred in the peeled portion and the intestine in dogs that were closed without placing an anti-adhesion membrane.

(Evaluation 2: Solubility)
When 1 g of the water-insoluble film produced in Example 1 was immersed in a 10% aqueous sodium carbonate solution, it dissolved after 30 minutes. On the other hand, when 1 g of the water-insoluble film produced in Example 1 was immersed in water, it did not dissolve even after 30 minutes and remained in its original form. From the above, it was confirmed that the water-insoluble membrane of this embodiment was neutralized in the presence of a sodium salt (sodium ion), and the carboxy group of hyaluronic acid was neutralized and gradually changed into soluble hyaluronate.

(Evaluation 3: Degradability)
1 g of the water-insoluble membrane produced in Example 1 was immersed in a 5000 unit / mL hyaluronidase aqueous solution, placed in a shaker adjusted to 37 ° C., and shaken at 10 to 20 rpm. On the other hand, a control test was conducted in which 1 g of the water-insoluble membrane produced in Example 1 was immersed in a PBS buffer (pH 6.8), placed in a shaker adjusted to 37 ° C., and shaken at 10 to 20 rpm. After 5 days, the water-insoluble film immersed in the PBS buffer remained in its original form, but the water-insoluble film immersed in the hyaluronidase aqueous solution was completely dissolved. It can be said that the water-insoluble membrane of this embodiment has been degraded by hyaluronidase because it retains the hyaluronic acid skeleton. From the above, it is presumed that the water-insoluble membrane of this embodiment is metabolized by the same metabolic pathway as that of water-soluble hyaluronic acid even when placed in a living body.

(Evaluation 4: Long-term solubility test)
The water-insoluble membrane produced in Example 1 was cut into 2 cm squares, placed in a container having a diameter of 3.5 cm and a depth of 1.5 cm, and 5 mL of PBS buffer (pH 6.8) was added. This container was put into a shaker adjusted to 37 ° C. and shaken at 10 to 20 rpm. As a result, it was found that the original shape of the film was retained even after 3 months.

  From the above, it can be seen that the water-insoluble molded product of the present invention remains water-insoluble for a long time in a PBS buffer. On the other hand, it can be seen that the water-insoluble molded product of the present invention is dissolved by the influence of in vivo pH, salt concentration, degrading enzyme, and the like. For this reason, the water-insoluble molded product of the present invention is suitable as a biodegradable or bioabsorbable medical material.

  The water-insoluble molded product of the present invention is useful as a medical material, a food material, a cosmetic material, and the like.

Claims (9)

  A raw material molded body formed using a water-soluble salt of a polyanionic polysaccharide is brought into contact with the vapor of at least one of an organic acid and an organic acid anhydride to insolubilize the raw material molded body, thereby forming a water-insoluble molded body. A method for producing a water-insoluble molded article having a forming step.   The water-insoluble molded product according to claim 1, wherein the polyanionic polysaccharide is at least one selected from the group consisting of carboxyalkyl cellulose, carboxymethyl starch, chondroitin sulfate, hyaluronic acid, heparin, alginic acid, pectin, and carrageenan. Manufacturing method. The organic acid is at least one of acetic acid and propionic acid;
The method for producing a water-insoluble molded product according to claim 1 or 2, wherein the organic acid anhydride is at least one of acetic anhydride and propionic anhydride.   The method for producing a water-insoluble molded product according to any one of claims 1 to 3, wherein the shape of the raw material molded product is a powder, a particle, a film, a lump, a fiber, a tube, or a sponge.   The water-insoluble molded object manufactured by the manufacturing method as described in any one of Claims 1-4.   The water-insoluble molded product according to claim 5, which is in the form of powder, particles, film, lump, fiber, tube, or sponge.   The water-insoluble molded article according to claim 5 or 6, which is a medical material, a food material, or a cosmetic material.   The manufacturing method of the adhesion prevention material which has the process of making a water-insoluble molded object of Claim 5 or 6 hold | maintain a polyhydric alcohol or polyhydric-alcohol aqueous solution.   The adhesion prevention material manufactured by the manufacturing method of Claim 8.