JPS6144081B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for insolubilizing or acylating a de-N-acetylated product of carboxyalkyl chitin or carboxyalkyl chitin salt, which is a soluble chitin derivative. More specifically, the present invention relates to a method for producing an insoluble chitin derivative, which comprises treating carboxymethyl chitin or a de-N-acetylated product of carboxymethyl chitin salt with an organic acid anhydride. The fiber components of polysaccharides that exist in nature can be roughly divided into collagen in higher animals, chitin in arthropods and lower plants, and cellulose in higher plants. is making. Among these, chitin is N-acetyl-D
- It is a polymer substance consisting of 1,4-β bonds of glucosamine, and exists in an amount comparable to that of cellulose. However, since chitin is extremely highly crystalline and its aminoacetyl groups have strong bonds, no economical solvent has yet been found that can dissolve, disperse, or swell chitin as well as alkali in cellulose. For this reason, the development of chitin's uses has lagged behind that of cellulose and other polysaccharides. Among them, Japanese Patent Publication No. 19213/1984 utilizes the property of chitosan, which is a de-N-acetylated product of chitin, to dissolve in dilute acid to produce a chitosan film, and then solid-phase acetylates the chitosan film. A method for obtaining a chitin film is disclosed. This method involves swelling a chitosan film in water, immersing it in a solvent such as ethanol, acetone, or pyridine, and N-acetylating it using a dehydration condensation agent for forming an amide group such as dicyclohexylcarboimide to form a chitin film. However, in this method, the time required for acetylation is extremely long, as seen in the examples below. In addition to the above-mentioned method, other methods for N-acetylation of chitosan have been reported, such as a method in which chitosan is reacted with acetic acid in a pyridine solvent, or a method in which chitosan is reacted with acetic anhydride-perchloric acid in a toluene medium. There is. However, these methods also have the disadvantage that the N-acylation time is long and the reaction rate is extremely slow, especially when chitosan contains water. All of the above-mentioned methods are aimed at obtaining a film-like material of chitin, and the use of the film-like material only suggests application to acoustic diaphragms, and the properties of chitin and chitin derivatives are limited. This leaves some dissatisfaction in terms of true application development that takes advantage of the technology. In view of the above-mentioned current situation, the inventors of the present invention have conducted extensive research into applications that can fully demonstrate the properties of chitin and chitin derivatives, as well as industrial manufacturing methods for shapes that can be applied to those applications. Surprisingly, when a de-N-acetylated product of methyl chitin or its salt is reacted with an anhydride of an organic acid, an acylation reaction occurs instantly and an acylated product that is insoluble in water, acids, alkalis, or organic solvents is obtained. , the knowledge that a molded material obtained by acylating at least a portion of a soluble chitin derivative obtained using this reaction has functions as a separation material, a dialysis material, a base material for immobilized enzymes, and an adsorbent. This is what led to the present invention. Based on the above findings, the present invention is based on the de-Nation of carboxymethyl chitin or carboxymethyl chitin salt.
- It consists of reacting a soluble chitin derivative such as an acetylated product with an anhydride of an organic acid alone or a mixture of an anhydride of the organic acid and an organic acid, and includes water,
The present invention provides a modified chitin (hereinafter referred to as an acylated product of a soluble chitin derivative) that is insoluble in acids, alkalis, or organic solvents. The soluble chitin derivative according to the present invention refers to the de-N-acetylated soluble (water-soluble) carboxyalkyl chitin or carboxyalkyl chitin salt disclosed in JP-A-55-90505, which the present inventor filed on the same day as the present application. For example, chitin is immersed in a highly concentrated alkaline aqueous solution, the chitin-immersed alkali aqueous solution is subjected to freezing treatment, and then the frozen alkali-containing chitin is converted into a compound of the formula X (CH ₂ )nCOOH (in the formula,
X represents Br or Cl, n represents an integer of 1, 2 or 3) An alkaline aqueous solution is added to the carboxyalkyl chitin obtained by reacting it in an organic solvent containing an etherifying agent. It can be produced by de-N-acetylation. One of the advantages of the method of the present invention is that the time required for the acylation reaction is extremely short even in the presence of water. However, the theoretical basis for this is still not clear, and it is presumed that the carboxyl group of carboxymethyl chitin or the de-N-acetylated product of carboxymethyl chitin salt itself plays the role of a catalyst. Due to this effect, molded materials in arbitrary shapes such as spherical, fibrous, and film shapes, or in hollow shapes as required, can be produced extremely easily and in a short time. The degree of substance permeability or swelling of the chitin-based molding material obtained by acylating at least a portion of the soluble chitin derivative obtained using the method of the present invention can be arbitrarily adjusted by changing the concentration of the soluble chitin derivative. obtain. According to the method of the present invention, since insolubilization occurs from the surface of the soluble chitin derivative solution, the permeability of the molding material is limited to some extent by the insoluble film that is initially formed. Since the chitin-based molding material obtained using the method of the present invention is made by acylating (insolubilizing) at least a part of a soluble chitin derivative, it is biologically and chemically stable and safe, and it is also a substance. Because of its excellent permeability, adsorption, and biocompatibility, it can be used as an encapsulation material, separation material, adsorption material, heavy metal collection material, drug sustained release material, base material for immobilized enzymes, ultrafiltration material, and biofunctionality. It can be applied to a wide range of applications such as materials, ion exchange materials, etc. The present invention will be explained in detail below. The raw materials for the soluble chitin derivative of the present invention are crab,
It is chitin represented by the general formula () obtained by separating and purifying the shells of arthropods such as shrimp by conventional methods. By reacting chitin with monochloroacetic acid or the like, it is carboxymethylated to become carboxymethyl chitin or a salt thereof containing a structural unit represented by the general formula (). Or Or (In the formula, M represents hydrogen, an alkali metal, an alkaline earth metal, or an ammonium group.) The carboxyalkyl chitin or its salt used in the method of the present invention has a carboxyalkyl group per unit of N-acetylglucosamine as a unit structure.
It has 0.1 to 1.0, preferably 0.3 to 1.0. If this is heated in an alkaline aqueous solution such as sodium hydroxide or potassium hydroxide, it is de-N-acetylated and a de-N-acetylated product of carboxyalkyl chitin or a salt thereof, that is, a soluble chitin derivative of the present invention is obtained. De-N-determination of soluble chitin derivatives of the present invention
Acetylation degree is 10-100%, preferably 20-60%
It is. When the degree of deacetylation is 60% or more, insolubilization tends to be delayed. However, the desired objective can be achieved by selecting reaction conditions such as increasing the reaction temperature. Insolubilization (acylation) of the soluble chitin derivative in the present invention is extremely simple. That is, by simply bringing an aqueous solution of the soluble chitin derivative into contact with an organic acid anhydride or a mixture of an organic acid anhydride and an organic acid, an acylation reaction occurs in an extremely short period of time as described above, and an insoluble chitin derivative is produced. be done. The organic acid anhydride or the mixture may be in the form of a solution or a gas, for example. Although the mechanism of this reaction is not yet clear, the reaction occurs instantaneously when the aqueous solution of the soluble chitin derivative comes into contact with the organic acid anhydride, and the reaction proceeds from the surface of the aqueous solution. A film consisting of the insoluble chitin derivative is formed, and the form of the aqueous solution is maintained, and then, after a slight delay, the organic acid anhydride diffuses into the interior through the initially formed insoluble chitin derivative film, and the reaction progresses internally. It is presumed that this promotes internal insolubilization. The reaction product at this time is N-acylated from the de-N-acetylated product of carboxymethyl chitin.
The main structural units are -acylated carboxymethyl chitosan (general formula), further decarboxymethylated N-acylated chitosan (general formula), and N-.O-acylated chitosan (general formula). :C ₆ H ₈ O ₃ ( _OCOR )・NHCOR :C ₆ H ₈ O ₃ (OH)NHCOR :C ₆ H ₈ O ₃ (OCOR)・NHCOR (In the formula, R is CH ₃ (CH ₂ ) _n and m is 0 to 4
However, the proportion of general formula () in the insolubilized material is usually 10% or less, and the remainder is occupied by general formulas () and (), making it insoluble in acids and alkalis. Further, as described below, depending on the use, it may be preferable to leave the structural unit of D-glycosamine, but even in this case, it remains insoluble. Note that the concentration of the aqueous solution of the soluble chitin derivative used in the present invention is generally 1 to 10 wt%, although the higher the concentration, the stronger and denser the insoluble chitin derivative will be. However, this should be adjusted as appropriate depending on the use and properties of the molding material of the present invention, and is not necessarily limited to this range. The organic acids and organic acid anhydrides used in the method of the present invention are preferably acetic acid, propionic acid, butyric acid, valeric acid, etc., and their anhydrides (hereinafter referred to as organic acid anhydrides). These may be used alone or as a mixture of two or more. The organic acid anhydride may be used as is without dilution, or the reaction rate may be adjusted or
For the purpose of facilitating treatment of the reactant, it may be diluted with an organic solvent that does not react with the organic acid or organic acid anhydride. The acylation reaction temperature is from 5 to 80°C, preferably from 5 to 60°C, but as mentioned above, when using a soluble chitin derivative with a degree of deacetylation of 60% or more, a higher temperature is desirable. Furthermore, when reacting with the organic acid anhydride gas, the temperature may be even higher. Next, an aqueous solution of a soluble chitin derivative and an organic acid anhydride are brought into contact with each other, and this can be appropriately selected depending on the use and form of the chitin-based molding material of the present invention. For example, one contact mode may include a method in which an aqueous solution of a soluble chitin derivative is dropwise dispersed in an organic acid anhydride while stirring. In this embodiment, an acylated product of a soluble chitin derivative, that is, an insoluble chitin derivative of the present invention, is formed by instantaneously reacting and insolubilizing the aqueous solution droplet from the surface, and further reacting to the inside over time, and forming a spherical shape. A molded material is obtained. After reacting for a predetermined period of time, unreacted organic acid anhydrides are removed by separation and washing with water to obtain spherical bodies made of chitin-based molding material. The resulting spheres can have a wide range of diameters ranging from about 10 to 10,000 microns by adjusting the size of the droplets applied. The film thickness and compactness or hollow shape of insoluble chitin or insoluble modified chitin as a surface coating can be adjusted by changing the concentration of the aqueous solution of the soluble chitin derivative used, reaction time, reaction temperature, etc. It is usually 1 to 1,000 microns, and the density can be obtained with a permeation limit ranging from 500 to 400,000 in molecular weight. Further, by spraying the aqueous solution of the soluble chitin derivative into the gas phase of the organic acid anhydride, the surface layer is instantly acylated to form an insoluble film, which is then poured into the organic acid anhydride.
You can get tiny spheres. Another contact mode may include spinning an aqueous solution of a soluble chitin derivative through a nozzle into a liquid containing an organic acid anhydride. In this embodiment, threads are obtained that are partially insoluble from the surface layer,
By washing this with water, fibers made of chitin-based molding material can be obtained. Furthermore, if a slit-shaped nozzle is used as the nozzle, it is also possible to obtain a film made of a chitin-based molding material. In both the fibrous and film forms, the interior can be made hollow and the film thickness and density can be adjusted as necessary, as in the case of spherical objects. It goes without saying that the contact mode is not limited to the above-described contact mode, and that various other contact modes can be adopted. As is clear from the above explanation, by using the method of the present invention, it is possible to easily produce chitin-based molded materials in any shape such as spheres, fibers, films, etc., and even in hollow bodies as required. Moreover, the chitin-based molding material is chemically permeable to substances.
Since it is composed of an acylated soluble chitin derivative that is biologically stable and safe, it can be applied to a wide range of uses other than those described above. To give an example of some of the uses, by putting a spherical molding material into a mixture sample solution using the permeability of the membrane, only substances with a certain molecular weight or less can be diffused into the molding material. It is also possible to use hollow fibers or films in the same manner as conventional dialysis materials. Furthermore, it can be used as an ion exchanger by taking advantage of its ability to control substance permeability and having an ionic group. In addition, it is extremely stable and safe for living organisms, so it can be used in biological fields, such as adsorbents or coatings such as adsorbents for blood perfusion or for adsorbing and removing toxins in the gastrointestinal tract. It can also be used as Furthermore, by dispersing the enzyme in a soluble chitin derivative, an encapsulated immobilized enzyme can be obtained. In addition, when used for purposes that involve contact with blood,
It is even more preferable to adjust the acylation reaction, leave some amino groups, and create a polyion with the amino groups and an antithrombotic substance such as heparin, chitosan sulfate, or chitin sulfate. In addition, if various ion exchange resins are contained in the molding material of the present invention, a new ion exchanger that has ion exchange ability only for substances with a specific molecular weight or less covered with a chitinous membrane will be created. If an adsorbent such as activated carbon is coated with the molded article of the present invention, it can become an adsorbent with novel performance not seen before. Hereinafter, the present invention is an epoch-making method that makes it possible to effectively utilize chitin, which has hitherto been a resource of limited use, and has countless potential applications. The present invention will be explained in more detail with reference to Examples below. Example 1 De-N-acetylated product of carboxymethyl chitin (degree of carboxymethylation 1.0, degree of deacetylation 50)
%) was dissolved in 950 g of water to a concentration of 5%, and then added dropwise to a mixed solution of acetic anhydride (5) and acetic acid (1), followed by stirring and dispersion. The reaction temperature was 25°C and the reaction time was 10 minutes to obtain an insoluble substance, which was washed with water to obtain a spherical substance with a diameter of 20 to 100μ. Furthermore, this was gradually replaced with ethanol,
Finally, the mixture was replaced with acetone and then dried. Yield: 48g 10g of the dried product was taken, ground, and then poured into 100cc of a 5% aqueous sodium hydroxide solution and stirred. After neutralizing this, insoluble matter is washed with water,
Furthermore, it was washed with ethanol and dried. The liquid was concentrated using an evaporator and then freeze-dried, but there was no residue. The results of elemental analysis of the dried product are shown in Table 1, and for reference, the elemental analysis values of chitin and the deacetylated product of carboxymethyl chitin used are also shown.

[Table] As is clear from the table, the insolubilized material was found to be composed of chitin. Example 2 Deacetylated product of carboxymethyl chitin (degree of carboxymethylation 0.5, degree of deacetylation 25%)
After dissolving 20 g in 180 c.c. of water, the solution was degassed under reduced pressure to prepare an aqueous raw material solution. A fibrous chitin-based molding material was obtained from the raw material aqueous solution using the apparatus shown in FIG. An anhydrous propionic acid solution maintained at 20°C is used in the reaction tank, and the raw material discharge pressure is 2 kg/cm ² . When the obtained fibers were analyzed in the same manner as in Example 1, no water-soluble substances were found, indicating that the fibers were made of insolubilized substances. Table 2 shows the elemental analysis values.

[Table] Example 3 17 g of the dried product obtained in Example 1 was swollen in distilled water, packed into a column with a diameter of 2 cm, and a gel permeability test was conducted. A mixed sample of 20 mg of bulldextran (molecular weight: 2 million) dissolved in 2 c.c. of distilled water and 30 mg of glucose was added to this column, and a sample of 30 mg of glucose was added to the column.
Elution was performed at cc/min. Bulldextran eluted in the eluate at 30-45 c.c., and glucose eluted at 65-80 c.c. Apparently, this spherical material has the ability to exfoliate, and the molecular weight
It turns out that the 2 million substances are not diffused inside the sphere. Example 4 A spherical material was produced according to Example 1 except that the raw materials, their concentrations, acylating agents, and reaction conditions were changed. The conditions and results are shown in Table 3. As is clear from these results, it can be seen that the acylation reaction according to the method of the present invention is carried out in an extremely short time.

【table】 [Brief explanation of the drawing]

FIG. 1 shows a schematic diagram of the spinning apparatus used in Example 2. 1... Water-soluble chitin derivative aqueous solution tank as raw material, 2
...Nozzle (25 holes, 0.05m/mφ), 3...Reaction tank (50m/mφ×3000m/mL), 4...Roller, 5...Solvent removal tank (first) Ethanol: Water =
1:1, 6...Solvent removal tank (second) water 100℃, 7
...Sowing device.

Claims (1)

[Scope of Claims] 1. A method for producing an insoluble chitin derivative, which comprises treating a de-N-acetylated product of carboxyalkyl chitin or a salt thereof with an organic acid anhydride alone or in a mixture with an organic acid. 2. The method according to claim 1, wherein the anhydride of the organic acid alone or in a mixture with the organic acid is a solution or a gaseous substance. 3. The de-N-acetylated product is a de-N-acetyl compound of carboxymethyl chitin or carboxymethyl chitin salt.
- The method according to claim 1 or 2, wherein the method is an acetylated product. 4. The method according to any one of claims 1 to 3, wherein the degree of de-N-acetylation of the de-N-acetylated product is 10 to 100%, preferably 20 to 60%. Method. 5. Claim 3, wherein the carboxymethyl chitin or carboxymethyl chitin salt has 0.1 to 1.0, preferably 0.3 to 1.0 carboxyl groups per N-acetyl-D-glucosamine structural unit. or the method described in Section 4. 6. The organic acid anhydride according to any one of claims 1 to 5, wherein the organic acid anhydride is one of acetic acid, propionic acid, butyric acid, and valeric acid anhydrides or a mixture thereof. Method.