JP2003292501A - Chitosan sponge and method for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a chitosan sponge which is useful in uses of cosmetics, medical materials, industrial materials, etc., has excellent physical properties such as strengths, etc., by an inexpensive method at a cost of about 1/10 of that of a conventional method. <P>SOLUTION: The method for producing the chitosan sponge comprises subjecting chitosan dissolved in an aqueous solution of an acid to vacuum-freeze- drying as it is or neutralizing the solution with an alkali and then subjecting the chitosan to vacuum-freeze-drying or further generally drying the chitosan to remove the acid. The chitosan sponge is obtained by the method. The method for producing the chitosan sponge comprises adding a softening agent to the chitosan dissolved in the aqueous solution of the acid. The chitosan sponge is obtained by the method. The chitosan sponge is useful in uses such as a food packaging paper, a wound covering material, a face pack material, etc. <P>COPYRIGHT: (C)2004,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention mainly relates to cosmetics,
The present invention relates to a sponge of chitosan that can be used in applications such as medical materials and industrial materials, and a method for producing the sponge.

[0002]

2. Description of the Related Art In recent years, chitosan has been widely used in the cosmetics field, medical field, food field and the like. Since chitosan dissolves in an acid such as acetic acid, various molded bodies can be prepared from the solution. For example, there are fibers, films, sponges, and the like, which have the possibility of being preferably used especially in the fields of cosmetics, medical care, foods, and the like. In particular, sponge is particularly useful because it is flexible and has high water absorption. The conventional method for producing a chitosan sponge is to foam a chitosan solution by a surfactant, a chemical foaming agent, gas blowing or the like to coagulate it, or to add a powdery solid substance to the chitosan solution and disperse it well before coagulating. Then, a method of removing the powdered solid substance has been proposed. In particular, the method of using this powdery solid component is to mix a water-soluble polymer, for example, polyvinyl alcohol powder and coagulate it, and then elute polyvinyl alcohol with hot water while maintaining the shape. Is the way to get.
These methods have been proposed in Japanese Patent Laid-Open No. 62-167331.

[0003]

However, the process for producing the chitosan sponge according to the conventional method is very complicated because it requires a lot of time and energy during the elution process. Therefore, as a result, the cost is very high,
The physical properties such as strength were not sufficient, and despite the excellent properties such as biocompatibility and antibacterial property of chitosan, industrial production was difficult and it could not be put to practical use.

As a result of diligent efforts to solve these problems, the inventors of the present invention have surprisingly produced a chitosan sponge by a very simple method which has never been thought of before, are inexpensive, and have physical properties. Succeeded in finding an effective way to get a good one. Especially, the cost is about 1/10 of that of the conventional method, which is effective.

That is, a chitosan sponge and a method for producing the same are characterized in that chitosan dissolved in an aqueous acid solution is neutralized with an alkali as it is, or is freeze-vacuum dried, or further usually dried to remove the acid. is there.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will be described below. The chitosan in the present invention is a natural polymer obtained by deacetylating chitin (natural polysaccharide having N-acetylglucosamine as a repeating unit) obtained by purifying the exoskeleton of crustaceans such as crab and shrimp by alkali treatment. Is. Generally, chitin obtained by deproteinizing the exoskeleton of these crustaceans with an alkali such as caustic soda and decalcifying with an acid solution such as hydrochloric acid is further deacetylated with a high-concentration alkaline aqueous solution such as caustic soda. What is said. Generally, the degree of deacetylation of chitosan is 60% or more, and they have the property of being dissolved in water but not in acetic acid.

For example, 5 to 10 fresh red snow crab shells are used.
Deproteinization treatment was performed at 90 to 100 ° C. for about 3 hours by treatment with a dilute alkali solution such as a wt% sodium hydroxide aqueous solution, and 40 hours of chitin obtained by decalcification treatment with a dilute acid aqueous solution such as 2N hydrochloric acid for about 3 hours. ~ 60
It can be obtained by deacetylation by treatment in a concentrated alkali solution of about wt% for about 5 to 20 hours while maintaining the temperature of about 90 to 100 ° C. When impurities generated in the process are removed, white solid flakes are obtained, and ground flakes are generally called chitosan, and the deacetylation degree is 60% or more. The degree of deacetylation of chitosan used in the present invention is preferably 70% or more, more preferably 80% or more. Usually, 0.5 wt% concentration of chitosan obtained in these steps, 0.5 w
When the viscosity of the t% acetic acid aqueous solution is measured at a measurement temperature of 20 ° C. using a Brookfield viscometer, it is 10 to 500.
The value is about mPa · s.

The feature of the present invention resides in a very simple method of directly freezing a solution of chitosan and then drying it as it is. It is possible to freeze-dry the chitosan dissolved in an aqueous acid solution as it is or after neutralizing with an alkali, or by freeze-vacuum drying, or Furthermore, it is a method for producing a chitosan sponge, which is characterized in that it is usually dried to remove the acid. The manufacturing method of the present invention can be summarized as the following 3
One way. A method in which chitosan dissolved in an aqueous acid solution is directly placed in a container and freeze-dried. A method in which chitosan dissolved in an aqueous acid solution is neutralized with an alkali, and then placed directly in a container and freeze-dried. Chitosan dissolved in an aqueous acid solution is neutralized as it is or with an alkali, put in a container, freeze-dried under vacuum, and then usually dried to remove the acid.

The acid referred to in the present invention means an aqueous solution of hydrochloric acid, formic acid, acetic acid, citric acid or the like, and among them, an acetic acid aqueous solution is particularly preferable. Generally, an acid concentration of 0.2 to 5 wt% can be used,
Particularly, 0.5 to 3 wt% is preferable. The concentration of chitosan is generally 0.2 to 5 wt%, preferably 0.5 to 3 wt%. These are the factors that determine the density of chitosan sponge. The viscosity of these chitosan aqueous solutions is 5 to 2000 mPa · s at 20 ° C.

Chitosan sponge is prepared by directly freeze-drying these solutions, and various sponges can be prepared by putting the chitosan solution in a predetermined shape container during freeze-vacuum drying. For example, a sheet shape, a cylindrical shape, an eyebrow shape, etc. can be formed. In the case of a sheet, the solution is placed in a tray made of metal, plastic or the like and freeze-dried under vacuum. The thickness can be adjusted by the depth. For example, when using 0.1 cm to 5 cm, the thickness of the sponge produced is approximately the same as the depth of the tray. The cylindrical shape was prepared by putting the solution in a cylindrical container and having a diameter of 0.
The thing of 5-5 cm can be produced. When making a sponge, it is also possible to make a cloth impregnated with a processed cloth, a non-woven fabric, a woven fabric, etc. by immersing them in a chitosan solution and similarly freeze-drying. For example, if gauze is dipped in a chitosan solution to prepare it, a sponge-coated molded article is formed on the surface of the gauze.

As the freeze-vacuum dryer of the present invention, a commercially available general freeze dryer can be used. That is, any model may be used as long as it has the ability to remove water by reducing pressure while maintaining the temperature of the aqueous chitosan solution at a temperature below the freezing point. The freeze-vacuum drying conditions are generally a freezing temperature of about -40 ° C and a drying time of 16 to 24 hours. The density of the sponge produced differs depending on the conditions, but it is necessary to limit to particular conditions. Not something.

The chitosan sponge according to the present invention has a density of 0.005 to 0.2 g / cm ³ . These various densities can be produced by adjusting the concentration of the chitosan solution. Particularly in the case of the present invention, 0.008 to 0.1 g /
Those having a cm ³ can be preferably produced. The strength of the chitosan sponge obtained in the present invention is 1.5 to 7.0 N / cm.
² has an elongation of 1.8 to 22%, high strength, high elongation, uniform porosity, and good physical properties. The strength and elongation of the present invention were measured by the following methods. 2.5 cm wide sponge
Cut into 8 cm long strips, Shimadzu autograph, model: AG-100kNG, pulling speed 10 m
Strength and elongation are measured at m / min. Here, the strength was calculated by the strength per unit area (N / cm ² ). Strength (N
/ Cm ² ) = cutting strength (N) / cross-sectional area of test piece (c
m ² ) and elongation (%) were calculated by (elongation / initial length) × 100.

The acid remains as it is in the sponge obtained by the method (1). Therefore, this sponge dissolves when it comes into contact with water or an aqueous solution. Therefore, it can be used for applications such as exhibiting a sponge shape before contact and requiring the shape to collapse after contact, which requires an antibacterial effect.

On the other hand, the above method is a method of neutralizing the chitosan aqueous solution to remove free acid before freeze-drying, and the neutralization can be performed by adding an alkaline aqueous solution to the chitosan aqueous solution. At that time, neutralization is preferably performed by a method of gradually adding an alkali while stirring the solution while avoiding rapid gelation. For example, for neutralization, about 2N sodium hydroxide is added dropwise while stirring the chitosan aqueous solution at a slow speed. When a precipitate is partially formed, the dropping is stopped, the solution is stirred until it is dissolved, and sodium hydroxide of about 2N is added repeatedly to gradually approach neutrality. This is used as a solution because the whole solution can finally be made into a uniform neutralization solution or gel. The sponge can be produced in the same way as. The obtained sponge has the property of not dissolving in water because the acid has already been neutralized. Therefore, even in the presence of water, the shape is stable and it has good properties.

The method (1) can be carried out by the same method until the production of the sponge which is freeze-dried in vacuum, as described above.
After the sponge is prepared by freeze-vacuum drying in the above method, the residual acid is usually dried and removed. Normal drying is intended to remove normal water with a hot air dryer or a vacuum dryer. The temperature is room temperature to 100 ° C. and usually 12 to 4
The acid can be removed in 8 hours, preferably in 16 to 24 hours. The sponge obtained does not dissolve in water as well as the acid has been removed. Further, it has the same properties as that of density and strength.

The sponge obtained by the present invention may lack brittleness and be fragile and brittle depending on the specific density and strength of the sponge. In that case, polyethylene glycols, ethylene glycol, in the state of chitosan solution,
If a softening agent such as glycerin or an oil agent is added in an amount of about 0.01 to 5 wt% and the same production is performed, the sponge finally produced can have flexibility.

According to the present invention, the strength as a porous body is more stable than the conventional method, and the manufacturing cost is significantly reduced. The cost is about 1 of the conventional method.
/ 10 or less. Therefore, it can be widely used industrially as a general-purpose product. For example, it can be preferably used for cosmetics, medical materials, and industrial materials.

Further, in the method of the present invention, when a third component such as a drug, a cosmetic or a quasi drug is added at the time of the chitosan solution, a final sponge containing these third component can be easily prepared. . A sponge containing the third component can be produced, can be produced without deteriorating the physiological activity, and can retain a substance whose physiological activity is easily denatured by other chemical components or temperature in the sponge. .

By mixing and molding these drugs in chitosan sponge, the drugs can have a sustained release function. The chitosan sponge of the present invention has high water absorption. The water absorption of the chitosan sponge is measured, for example, by cutting the chitosan sponge into a length of 2.5 cm × 2 cm and a thickness of 0.4 cm, putting it in a polyethylene tea bag, and immersing it in pure water for 10 minutes, and then each tea bag It can be done by pulling out from pure water, draining water until no water drops fall, and measuring the weight. Water absorption rate (%) is {weight of sponge after water absorption (g) / weight of sponge before water absorption (g)} ×
It can be calculated as 100. The chitosan sponge of the present invention has a very high water absorption rate and is 40 to 40% of its own weight.
It was able to absorb about 50 times as much water and had excellent water absorption. The contents of the present invention will be described in detail below with reference to examples.

[0020]

Example 1 Red snow crab shells were crushed to about 2 to 5 cm, deproteinized with a 5 wt% caustic soda solution for 3 hours at 90 ° C., and further with a 6% (w / v) hydrochloric acid solution at 25 ° C. for 3 hours. Chitin flakes were obtained by decalcination for a period of time. After drying, while maintaining the temperature of 90 ° C. in a 48 wt% sodium hydroxide solution,
After time treatment, flaky chitosan was obtained.

This was crushed to prepare a powder of 80 mesh pass. The degree of deacetylation was measured by the colloid titration method (chitin, chitosan experiment manual, pages 51-52, edited by chitin and chitosan research society, Gihodo Publishing Co., Ltd.), and was 88.0%.
Met. Further, the viscosity of 0.5 wt% chitosan in a 0.5 wt% acetic acid solution at 20 ° C. is 50 mPa · s, and the GPC measuring device (system: manufactured by JASCO, column: Shodex
OHpak SB-805, SB-806, mobile phase;
0.5 M acetate buffer, column temperature: 40 ° C., flow rate: 1.
A calibration curve was prepared and calculated based on the pullulan standard at 0 ml / min. ) Was estimated to be about 1,000,000.

This chitosan was dissolved in acetic acid solution to obtain 1.0
It was set to wt%. This solution was poured into a plastic tray (25 cm × 16 cm in length, 2 cm in depth), and a Kyowa lyophilizer (model; RLE-203S) was used for about −40.
After freezing at 2 ° C. for 2 hours, vacuum drying was performed for 16 hours to freeze-dry under vacuum to obtain a sponge-like sheet. The physical properties of this sheet are 25 cm x 16 cm in length, 0.4 cm in thickness,
Specific gravity 0.015 g / cm ³ , tensile strength 3.3 N / cm
² and the elongation was 6.6%. When this sponge sheet was used as a wrapping paper for food, the antibacterial effect of chitosan enabled long-term storage of food.

[0023]

Example 2 The chitosan sponge prepared in Example 1
It was dried under reduced pressure at 00 ° C. for 24 hours to remove residual acetic acid. Length 20 cm × 12 cm, thickness 0.4 cm, specific gravity 0.012 g / cm ³ , tensile strength 2.7 N / cm ² ,
The elongation was 7.2% and the water absorption rate was 4400 to 5500%, which was 44 to 55 times the own weight. The manufacturing cost was about 1/10 of the cost calculated from the process of the conventional method (Japanese Patent Laid-Open No. 62-167331). This sheet is 10 cm x 10
It was cut to a size of cm, sterilized with ethylene oxide gas, and used as a wound protection material. The chitosan sponge was applied as it was to a patient who had a bark wound (15/1000 inch depth) after the skin was taken for skin grafting. The sponge was easily attached to the wound surface, gauze was applied over it, and it was fixed with skin tape. Exudate was abundant after 1-2 days and moved to the gauze side, so when gauze was replaced, the wound surface dried after 10 days, the sponge peeled off after 14 days, and the wound was completely healed and the wound surface condition was also good. . Chitosan sponge has been shown to be good and effective as a wound protection material.

[0024]

Example 3 Chitosan was dissolved in a 1.0 wt% acetic acid solution to a concentration of 1.0 wt%. Polyethylene glycol (Daiichi Kogyo Seiyaku, PE
G400) was added and mixed. The 2N sodium hydroxide aqueous solution was added dropwise over 2 hours while stirring the chitosan aqueous solution at a slow speed. The pH of the solution after dropwise addition of 2N sodium hydroxide was 6.5. This chitosan aqueous solution was poured into a plastic tray (24 cm x 16 cm, depth 4 cm) and frozen at -40 ° C for 2 hours,
Freeze vacuum dried for 18 hours, specific gravity 0.06 g / cm ³ , width 2
A sponge-like sheet having a size of 4 cm × 16 cm and a thickness of 0.35 cm was obtained. The water absorption of this sponge-like sheet is 800-1
At 000%, the water absorption rate was 8 to 10 times that of the own weight. The sponge sheet was impregnated with lotion and used as a face pack material. The water retention of the lotion was also good, and the adhesion and touch to the skin were also good.

   ─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Tsubokura Kaji             44 Nishimachi, Saihaku-cho, Saihaku-gun, Tottori Prefecture (72) Inventor Nobuo Tadashi             1432 Wadamachi, Yonago City, Tottori Prefecture             Room 202 F-term (reference) 4C090 AA03 BA47 BD25 CA19 DA22                       DA26 DA31

Claims (3)

[Claims] 1. A chitosan dissolved in an acid aqueous solution as it is,
Alternatively, a method for producing a chitosan sponge, which comprises neutralizing with an alkali and then performing freeze-vacuum drying, or further usually drying to remove an acid. 2. The method for producing a chitosan sponge according to claim 1, wherein a softening agent is added to chitosan dissolved in an aqueous acid solution. ^3. A chitosan sponge having a density of 0.008 g / cm ^{3 to} 0.1 g / cm ³ obtained by the method of claim 1.