JP2826898B2 - Method for producing chitosan derivative - Google Patents

Description

The present invention relates to a process for producing a novel chitosan derivative having a specific N, N-dicarboxymethylglucosamine derivative as a constituent unit and having high ion-trapping ability and moisturizing action. About.

[Problems to be solved by conventional technology and invention]

Generally, detergents are produced by blending a surfactant with a detergent builder and other additives. As a detergent builder, condensed phosphate compounds such as sodium tripolyphosphate (STPP) have been widely used in terms of performance and price, but due to eutrophication of rivers and the like caused by an increase in the amount of phosphorus compounds on the surface and in water. Due to the occurrence of environmental problems, their replacement has been rapidly advanced in recent years.

As an alternative to this STPP, zeolites that have no problem in terms of eutrophication and safety have come to be used in recent years, but zeolites are insoluble in water and do not have the dispersing ability that STPP has . Therefore, the detergent containing this has a disadvantage that the cleaning power is inferior to the detergent containing STPP having chelating ability and dispersing ability, and that it cannot be incorporated into a liquid detergent.

In addition, studies have been made on water-soluble low molecular weight compounds having chelating ability for metal ions, and polyvalent carboxylic acids such as citric acid and succinic acid, and nitrogen-containing carboxylic acids such as nitrilotriacetic acid have been provided. However, although these low molecular compounds also have chelating ability,
Since it has no dispersing ability in water, the detergent containing the same had poor detergency.

Furthermore, in recent years, anionic polymer compounds have been used as detergent builders, which have both a chelating ability and a dispersing ability derived from the protective colloid effect of the polymer. Obtainable.
However, synthetic anionic polymer compounds are poor in biodegradability and have a problem in terms of environmental pollution, and although anionic polymer compounds derived from natural polymers such as carboxymethyl cellulose have some degree of biodegradability, However, there is a problem in that the degree of carboxymethylation during the reaction is limited, and the ability of each carboxyl group to chelate calcium ions is weak, so that it does not have a sufficient ability to sequester calcium ions.

Therefore, development of a detergent builder which has excellent chelating ability and dispersing ability, has good biodegradability and has no problem of environmental pollution has been desired.

In addition, hyaluronic acid has been receiving attention as a humectant for cosmetics and as a raw material for pharmaceuticals. Hyaluronic acid binds to a large amount of water to retain moisture in the skin and has the effect of softening the skin.It is also widely used as a raw material for cosmetics, ophthalmology and surgical drugs because it has a relationship with the lubricating effect of contact. Have been.

Conventionally, as a method for producing hyaluronic acid, there are known a method of isolating and purifying from a tissue in a living body such as chicken squirrel, and a fermentation method using a microorganism (Japanese Patent Application Laid-Open No. 58-56692). The former method is too costly, and the latter method has disadvantages such as requiring special equipment and technology.

Therefore, the development of an inexpensive humectant having performance equal to or higher than that of hyaluronic acid has been desired.

On the other hand, chitin, which is a raw material of chitosan, is N-acetyl-
D-glucosamine is a polysaccharide consisting of 1,4-linked,
It is present in supporting tissues such as crustaceans, insects, and fungi, and has the second highest production in nature after cellulose. However, chitin has an acetamido group in the molecule,
Since organized chitin is an extremely stable compound, its crystal structure is not as strong as that of cellulose, but is a polysaccharide with extremely poor processability and reactivity. Therefore, despite the fact that research began at about the same time as cellulose,
Little utility has been found, and most of the natural chitin is discarded. Therefore, if chitin can be recycled, it is extremely advantageous from the viewpoint of effective use of unused natural polymers.

In addition, chitosan obtained from chitin has only been used as a flocculant or the like as a cationic polymer compound derived from a natural polymer.

In addition, carboxymethylation of chitin and chitosan
In general, this is performed to ensure solubility in water in the neutral region.For example, U.S. Pat.No. 4,699,195 discloses that N, O-dicarboxymethyl is obtained by reacting monochloroacetic acid with chitosan under strong alkali in isopropyl alcohol. Pure & Appl. Chem., 54 , (11), 2141
(1982) discloses a method in which chitosan and glyoxylic acid are reacted to form an imine structure, and then reduced with a reducing agent such as NaBH ₂ CN to obtain N-carboxymethylated chitosan. Appl.22780A / 81 (1
7 , (2), 87 (1987), but none of the chitosan derivatives has sufficient chelating ability. In addition, chitosan is O-
Carboxymethylated compounds having improved chelating ability with heavy metals have also been developed [Polym. J., 15 , (8), 597 (1)
983)], but this was still not satisfactory.

In addition, N, N-dicarboxymethylated chitosan has not been obtained.

[Means for solving the problem]

Under such circumstances, the present inventors have conducted intensive studies. As a result, a novel N, N- compound was obtained by reacting a specific chitosan derivative with monohanogenoacetic acid or a salt thereof in a certain pH range.
The present invention has found that a dicarboxymethylated chitosan derivative can be produced, and that the obtained chitosan derivative has high ion-sequestering ability and moisturizing effect, has good biodegradability, and has no problem of environmental pollution. Was completed.

 The production method of the present invention is represented by the following reaction formula.

[Wherein X represents a halogen atom, R ¹ and R ² are the same or different and are each a hydrogen atom, a group —CH ₂ COOM ¹ , a group EO _p PO
_q H, (Wherein, M ¹ represents a hydrogen atom, an alkali metal atom, a trialkylammonium group or a quaternary ammonium group which may be substituted with a hydroxy group, and M ₂ represents a hydrogen atom, an alkali metal atom, an ammonium group, a hydroxy group Represents an alkyl ammonium group or a quaternary ammonium group which may be substituted, EO represents ethylene oxide, PO represents propylene oxide, p represents a number of 0 to 5, and q represents 0 to 5
Indicates the number of However, p and q do not simultaneously become 0), and R ³ represents a hydrogen atom or a group —CH ₂ COOM ¹ (M ¹ has the same meaning as described above). However, R ¹ and R ² are not hydrogen atoms at the same time. That is, the present invention relates to a chitosan derivative having a structural unit represented by the general formula (II), a monohalogenoacetic acid represented by the general formula (III) The present invention provides a method for producing a chitosan derivative having a N, N-dicarboxymethylglucosamine derivative represented by the general formula (I) as a constituent unit by reacting a salt at a pH of 6 to 11, followed by salt exchange as required. is there.

The starting compound in the production method of the present invention contains the chitosan derivative represented by the general formula (II) as a constituent unit in the molecule.

In the above formula, examples of the halogen atom represented by X include a chlorine atom, a bromine atom, and an iodine atom.

In the above formula, examples of the alkali metal atom represented by M ¹ include a lithium atom, a sodium atom, and a potassium atom.Examples of the trialkylammonium group that may be substituted with a hydroxy group include triethanolammonium. And a triisopropanol ammonium group.

In the present invention, the chitosan derivative serving as a raw material may contain a structural unit represented by the following general formula (IV) in addition to the structural unit represented by the general formula (II).

[Wherein, R ¹ and R ² have the same meaning as described above, and R ⁴ and R ⁵ are the same or different and are a hydrogen atom, a group —COCH ₃ , a group EO _p P
O _q H, (Wherein, M ¹ , EO, PO, p and q have the same meanings as described above). However, R ⁴ and R ⁵ are not hydrogen atoms at the same time.] In the present invention, the reaction between the chitosan derivative having the structural unit (II) and the monohalogenoacetic acid or its salt (III) is carried out in a solvent at pH 6 to 11. Done. When the pH is less than 6, that is, when the pH shifts to the acidic side, the amino group in the chitosan derivative becomes an ammonium group, and the reactivity with monohalogenoacetic acid (salt) decreases.

On the other hand, when the pH exceeds 11 and becomes alkaline, the reaction between monohalogenoacetic acid (salt) and the hydroxyl group in the chitosan derivative becomes dominant, and the reaction to the amino group is inhibited.

In this reaction, an acid such as hydrochloric acid is generated with the progress of the reaction.Therefore, it is preferable to use a base for the purpose of maintaining the pH of the reaction system in the above range.
For example, sodium hydroxide, potassium hydroxide, triethanolamine and the like can be mentioned.

The reaction solvent used is preferably an aqueous solvent, particularly preferably water. The reaction is preferably carried out with stirring, and is almost completed in 2 to 14 hours at a reaction temperature of room temperature to reflux temperature, preferably 60 to 100 ° C.

After completion of the reaction, the resulting reaction solution is centrifuged as necessary to remove insoluble unreacted chitosan derivative, and then poured into a hydrophilic organic solvent to obtain the desired N, N-diamine. A chitosan derivative having the carboxymethylglucosamine derivative (I) as a constituent unit can be obtained as a precipitate. Examples of the hydrophilic organic solvent used here include ketones such as acetone and methyl ethyl ketone; and alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol and isobutanol.

Furthermore, the thus obtained chitosan derivative having the N, N-dicarboxymethylglucosamine derivative (I) as a constitutional unit can be used as it is, but if necessary, may be used after performing salt exchange. . Here, examples of the salt obtained by the salt exchange include an alkyl ammonium salt which may be substituted with a hydroxy group, such as an ammonium salt and a diethanol ammonium salt.

〔The invention's effect〕

According to the production method of the present invention, it has not been obtained until now.
N, N-dicarboxymethylated chitosan derivatives can be easily produced.

In addition, the chitosan derivative obtained by the production method of the present invention has good biodegradability and does not cause environmental pollution, and has a high ion-sequestering ability, so that it is useful as a detergent builder, and further has a high moisture retention. Since it has an action, it is also useful as a humectant for cosmetics, pharmaceuticals and the like.

〔Example〕

Hereinafter, the present invention will be described specifically with reference to Examples.
The present invention is not limited by these examples.

Example 1 O-carboxymethyl chitosan triethanol ammonium salt (degree of substitution 1.0) 9.2 kg (25.0 mmol), water 50 ml, monoethanol acetate triethanol ammonium salt 14.9 g (100 mm
ol) is weighed into a 300 ml flask and magnetically stirred at 80 ° C. Since the system became acidic with the progress of the reaction, triethanolamine was gradually added from the dropping funnel to maintain the pH of the system at 7. After reacting at 80 ° C. for 6 hours, the reaction solution was adjusted to pH 11 with triethanolamine, and then poured into a large amount of methanol for reprecipitation. The precipitate was taken out and dried under reduced pressure to obtain 12.0 g of O, N, N-carboxymethylated chitosan triethanol ammonium salt as a light brown powder.

Example 2 Partially phosphorylated chitosan sodium salt (degree of substitution 1.0) 7.1
g (25.0 mmol), water 50 ml, sodium monochloroacetate 11.
7 g (100 mmol) is weighed into a 300 ml flask and stirred at 80 ° C. Since the system became acidic with the progress of the reaction, a 5N aqueous sodium hydroxide solution was gradually added from the dropping funnel to maintain the pH of the system at 7. After reacting at 80 ° C. for 6 hours, the reaction solution was poured into a large amount of methanol and reprecipitated. The precipitate was taken out and dried under reduced pressure to obtain 7.1 g of N, N-carboxymethylated phosphorylated chitosan sodium salt as a powder.

Example 3 6.2 g (25.0 mmo) of chitosan sulfate (degree of substitution 1.0)
l), water 50ml, sodium monochloroacetate 11.7g (100mmo
l) is weighed into a 300 ml flask and stirred at 80 ° C. The system becomes acidic as the reaction progresses.
The pH of the system was maintained at 7 by slowly adding a 5N aqueous sodium hydroxide solution. After reacting at 80 ° C. for 6 hours, the reaction solution was poured into a large amount of methanol and reprecipitated. The precipitate was taken out and dried under reduced pressure to obtain 7.1 g of N, N-carboxymethylated chitosan sulfate sodium salt as a powder.

Test Example 1 Determination of carboxyl group The content of carboxyl group was determined by colloid titration. Table 1 shows the results.

Test Example 2 Measurement of calcium ion chelating ability Calcium ion chelating ability was measured at pH 10 using a calcium ion electrode. Table 2 shows the results.

From the results shown in Table 2, it can be seen that the chitosan derivative obtained according to the present invention has excellent calcium ion trapping ability.

Test Example 3 Measurement of the rate of increase in moisture absorption and the rate of residual moisture The rate of increase in moisture absorption and the rate of residual moisture were measured by the following methods. Table 3 shows the results.

(Moisture absorption increase rate)

A desiccator having a relative humidity of 81% with a saturated aqueous solution of ammonium sulfate and a desiccator having a relative humidity of 43% with a saturated aqueous solution of potassium carbonate were prepared in a 20% constant temperature room, and 0.5 g of a dried sample was precisely weighed in a beaker having a diameter of 3 cm and left in the desiccator. The rate of increase in moisture absorption was determined from the weight of the sample after standing according to the following equation.

Rate of increase in moisture absorption (%) = [(Wn−WO) / WO] × 100 WO: weight before standing Wn: weight after standing [water remaining rate] 0.5 g of each sample was precisely weighed in a beaker having a diameter of 3 cm, and then the sample was weighed. About 10% by weight of water was added to the sample, and the mixture was placed in a desiccator at 43% relative humidity with a saturated aqueous solution of potassium carbonate.
Left at 40 ° C. for 40 hours. After standing, each sample was precisely weighed, and the residual moisture ratio of the following formula was determined as an index of moisture retention.

Water remaining rate (%) = (Hn / HO) × 100 = [(Wn−S) / (WO-S)] × 10
0 HO: Water content added Hn: Water content after standing WO: Weight of water-containing sample before standing Wn: Sample weight after standing S: Dry sample weight From the results shown in Table 3, it can be seen that the chitosan derivative obtained according to the present invention has the same level of water retention as hyaluronic acid.

Claims (1)

(57) [Claims] 1. The following general formula (II) Wherein R ¹ and R ² are the same or different and are each a hydrogen atom, a group-
CH ₂ COOM ¹ , group EO _p PO _q H, (Wherein, M ¹ represents a hydrogen atom, an alkali metal atom, a trialkylammonium group or a quaternary ammonium group which may be substituted with a hydroxy group, EO represents ethylene oxide, PO represents propylene oxide, and p represents indicates the number of 0 to 5, q is a number of 0-5. Here, p and q indicates are not 0 at the same time), R ³ is a hydrogen atom or a group -CH
₂ COOM ¹ (M ¹ has the same meaning as above). However,
R ¹ and R ² are not hydrogen atoms at the same time.] The following general formula (III) X-CH ₂ COOM ¹ (III) wherein X is a halogen atom Wherein M ¹ has the same meaning as described above], wherein a monohalogenoacetic acid or a salt thereof represented by the following formula is reacted at pH 6 to 11, and then, if desired, is subjected to salt exchange. [In the formula, M ² represents a hydrogen atom, an alkali metal atom, an ammonium group, an alkyl ammonium group or a quaternary ammonium group which may be substituted with a hydroxy group, and R ¹ and R ² have the same meaning as described above.] A method for producing a chitosan derivative having a N, N-dicarboxymethylglycosamine derivative represented by the following formula as a constituent unit.