JP2511676B2 - Process for producing oxide of polyoxyethylenated chitin - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for producing a highly pure water-soluble polyoxyethylenated chitin oxide, which is useful as a raw material for cosmetics, pharmaceuticals, etc. and which can substitute for hyaluronic acid. is there.

2. Description of the Related Art In recent years, hyaluronic acid has attracted attention as a moisturizing agent for cosmetics and a raw material for pharmaceuticals. Hyaluronic acid binds to a large amount of water to form a gel, has the effect of retaining skin moisture and softening the skin, and is related to the lubrication action of joints, and is widely used in cosmetics, ophthalmic / surgical raw materials. It is used.

Conventionally, as a method for producing hyaluronic acid, a method of isolating and purifying from glass tissues of cattle eyes, chicken goshawk, umbilical cord and other in vivo tissues, and a fermentation method using a microorganism of the genus Streptococcus (JP-A-58). -56692) is known. The former method is extremely expensive, and the latter method has the drawback of requiring special equipment and technology. Therefore, there is a need for an inexpensive alternative that has the same performance as hyaluronic acid.

Problems to be Solved by the Invention The present inventors have noticed that hyaluronic acid is a kind of mucopolysaccharide in which glucuronic acid and N-acetylglucosamine are bound, and the structure of the mucopolysaccharide is similar to that of mucopolysaccharide. The present invention has been completed by conducting intensive research using chitin as a raw material for a hyaluronic acid substitute.

An object of the present invention is to provide a hyaluronic acid substitute which is industrially producible and inexpensive.

Means and Actions for Solving Problems The above problems are solved by the present invention. That is, the present invention relates to a method for producing an oxide of polyoxyethylenated chitin, which comprises oxidizing an aqueous solution of polyoxyethylenated chitin with an oxygen-containing gas in the presence of a noble metal catalyst.

Chitin is a kind of mucopolysaccharide widely distributed in tissues of lower animals such as crustaceans such as shrimps and crabs from fungi / algae, and is a naturally occurring macromolecule that is naturally abundant along with cellulose. Since chitin is extremely stable and insoluble in water and various organic solvents, it has conventionally been scarcely used and discarded.

Polyoxyethylenated chitin as a starting material in the method of the present invention, active hydrogen general formula chitin - with _{(CH 2 CH 2 O) m} -H (I) [wherein m represents an integer of 1 to 5] Substituted chitin obtained by a general purification method from shells of shrimp, crab and the like containing chitin may be polyoxyethylenated. Since chitin is micellar and does not easily react as it is, it is necessary to carry out a polyoxyethylenation reaction after treatment such as alkali chitinization.
The method for preparing alkaline chitin is to dilute chitin in concentrated alkaline aqueous solution such as sodium hydroxide or potassium hydroxide and then filter and wash to dilute to a predetermined alkaline concentration, or disperse chitin in concentrated alkaline aqueous solution. Then freeze it.

In order to polyoxyethylenate chitin, general formula (I) ′ H- (OCH ₂ CH ₂ ) m—X (I) ′ [wherein X represents a chlorine atom or a bromine atom, and m is 2 to
Which represents an integer of 6], or at least one halogenated polyoxyethylene compound represented by the formula, or ethylene oxide or ethylene chlorohydrin may be reacted.

Oxidation of polyoxyethylenated chitin takes place in aqueous solution at pH 6.
It is carried out by contacting with an oxygen-containing gas in the presence of a noble metal catalyst at a temperature in the range of 5 to 11.0 and room temperature to 100 ° C. The reaction time is usually 2 to 50 hours.

The noble metal catalyst used in the oxidation reaction is preferably a noble metal oxidation catalyst such as platinum carbon or palladium carbon.

After completion of the reaction, by neutralizing and desalting by dialysis membrane treatment or the like, an oxide of polyoxyethylenated chitin having a constant molecular weight distribution and few impurities can be obtained.

Oxides of polyoxyethylenated chitin obtained by the method of the present invention, the terminal hydroxyethyl group of the polyoxyethylene group is oxidized general formula _{(II) - (CH 2 CH} 2 O) n-CH 2 COOM ( II) [wherein M represents a hydrogen atom or an alkali metal, and n represents an integer of 0 to 4], and a polyoxyethylene carboxymethyl group represented by the formula, which has a water retention effect similar to that of hyaluronic acid. The compound is suitable as a raw material for cosmetics and pharmaceuticals.

Example 1 10 g of purified chitin powder was dispersed in 40 ml of an aqueous sodium hydroxide solution (concentration 40%) containing 0.2% sodium lauryl sulfate, and then frozen at -20 ° C and allowed to stand for 24 hours to obtain alkaline chitin. Next, the frozen alkaline chitin was stirred and dispersed in 200 ml of isopropanol at room temperature, and 60 g of ethylene chlorohydrin was sequentially added and reacted for 24 hours. After completion of the reaction, the reaction product is dissolved in a large amount of water, neutralized, added with acetone to precipitate and separated by a centrifuge, then dissolved in water again and desalted with a large amount of water through a dialysis membrane to leave the residue. The liquid was concentrated to obtain 8.5 g of hydroxyethyl chitin. The result of elemental analysis was C: 43.90, H: 6.69, N: 5.98, and the calculated value (C: 48.58, H: 6.8
The degree of substitution calculated from (8, N: 5.68) was 0.72.

Dissolve 0.5 g of hydroxyethyl chitin in 30 ml of water, put in a reaction vessel with a stirrer, adjust to pH 8 with sodium carbonate, add 0.15 g of platinum carbon catalyst and blow oxygen at 70 ml / min, and at a temperature of 90 ° C for 24 hours. Reacted for hours. After completion of the reaction, the catalyst was filtered off, concentrated and dialyzed to give carboxymethyl chitin.
Got 5g. When the degree of oxidation was determined by potentiometric titration, it was 0.
It was 15. The water retention effect of the obtained carboxymethyl chitin was compared with that of sodium hyaluronate and urea. The method for measuring the water retention effect is as shown below.

[Moisture absorption test method] 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 thermostatic chamber at 20 ° C, and each dried sample was crystallized to have a diameter of 4.5 cm. 1 g was precisely weighed on a plate and left in a desiccator. After leaving for 40 hours, the weight of each sample was precisely weighed. The moisture absorption amount was determined as the rate of increase by the following equation from the weight measured after standing.

Moisture absorption increase rate = [(Wn-Wo) / Wo] x 100 Wo: Weight before leaving Wn: Weight after leaving [Humidity test method] After adding about 10% water to each sample, add it to the crystal dish. The sample was weighed, placed in a desiccator containing a saturated aqueous solution of potassium carbonate (relative humidity 43%), and left in a thermostatic chamber at 20 ° C. After 40 hours of standing, each sample was precisely weighed. The water retention rate of the following formula was used as an index of moisturizing property.

Moisture residual rate = (Hn / Ho) x 100 = [(Wn-S) / (Wo-S)] x 100 Ho: amount of added water Hn: amount of water after leaving Wo: weight of water-containing sample before leaving Wn: leaving Subsequent sample weight S: Dry sample weight Table 1 shows the measurement results.

From the results shown in Table 1, it can be seen that the polyoxyethylenated chitin oxide obtained by the method of the present invention is a compound having a water retention capacity comparable to that of hyaluronic acid.

EFFECTS OF THE INVENTION According to the method of the present invention, an oxide of polyoxyethylenated chitin having a water retention effect equivalent to that of hyaluronic acid can be industrially produced at low cost.

Claims (2)

(57) [Claims] 1. A method for producing an oxide of polyoxyethylenated chitin, which comprises oxidizing an aqueous solution of polyoxyethylenated chitin in contact with an oxygen-containing gas in the presence of a noble metal catalyst. 2. The method according to claim 1, wherein the noble metal catalyst is a palladium carbon catalyst or a platinum carbon catalyst.