JPH07118305A - Production of fine spherical chitosan particle - Google Patents

Abstract

PURPOSE:To obtain fine spherical porous chitosan particles with an average particle size of 0.1-50mum. CONSTITUTION:Fine spherical chitosan particles are obtd. by injecting a W/O emulsion of an acidic aq. chitosan soln. into an org. solvent optionally contg. a base to coagulate the emulsion to thereby deposit the particles.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing spherical chitosan fine particles, and more specifically, spherical chitosan having a particle size of about 0.1 to 50 μm, which is suitable for catalyst carriers, chromatography fillers, powders for cosmetics and the like. The present invention relates to a method for producing fine particles.

[0002]

BACKGROUND OF THE INVENTION Chitosan consists of shrimp, crab, chitin, which is a constituent of the crust of crustaceans such as insects, in an alkaline aqueous solution of 30 to 50% by weight at a temperature of 60 ° C or higher. It is a basic polysaccharide having D-glucosamine as a basic skeleton, which is obtained by heating to deacetylation. Since chitosan has a polar group in its skeleton, it has a highly crystalline structure due to the formation of hydrogen bonds. Therefore, although it is not dissolved in a general organic solvent, it is possible to form and dissolve a salt in an acidic aqueous solution such as acetic acid or hydrochloric acid. Therefore, in order to make chitosan into fine particles, a method of making chitosan into an acidic aqueous solution and then coagulating it has been proposed so far.

Conventionally known methods for producing fine chitosan particles include a method of dropping a chitosan acidic aqueous solution into an alkaline aqueous solution using a nozzle, a method of forming a chitosan acidic aqueous solution, and spraying and drying in a high temperature atmosphere, chitosan. A method is known in which an acidic aqueous solution is mixed with a hydrophobic solvent and emulsified to form an emulsion, which is then poured into an alkaline aqueous solution to coagulate.

For example, JP-A-61-40337 and JP-A-61-40337
No. 61-76504 discloses that chitosan microparticles having a uniform particle size can be produced by dropping an acidic aqueous chitosan solution into a basic solution at a constant rate with a pressurized air using a nozzle and solidifying the solution. With this method,
It is possible to produce spherical particles having a relatively large particle size with an average particle size of 50 to 500 μm. Japanese Patent Application Laid-Open No. 62-210101 discloses a method in which an acidic aqueous chitosan solution is sprayed in a high temperature atmosphere, dried, and then neutralized with a basic solution. According to this method, fine particles having an average particle size of about 50 μm can be produced, but chitosan fine particles having irregularities on the surface, which are different from spherical particles, are obtained.

JP-A-3-9925 and JP-A-3-9926 describe a chitosan acidic aqueous solution containing polyethylene glycol,
Polymethacryloxyethyl ammonium chloride,
A method for preparing fine particles by preparing a chitosan dispersion liquid by mixing with a water-soluble polymer such as N, N-dimethyl-3,5-methylene-piperidin chloride and coagulating it is disclosed. . However, although fine particles having a relatively small average particle diameter can be obtained by this method, it does not become spherical.

Further, in Japanese Patent Laid-Open No. 58-57401, an emulsion is prepared by adding a hydrophobic solvent containing an emulsifier to a chitosan acidic aqueous solution and stirring the mixture sufficiently, and then the emulsion is poured into an alkaline aqueous solution while stirring. , A method for solidifying and precipitating spherical chitosan is disclosed. But,
When this method is used, particles are aggregated with each other and it is difficult to take out chitosan fine particles.

Therefore, the object of the present invention is to have an average particle size of 0.1 to
Another object of the present invention is to provide a method for obtaining spherical chitosan fine particles which are relatively small and have a size of about 50 μm.

[0008]

Means for Solving the Problems As a result of intensive studies to solve the above problems, the present inventors have found that an average aqueous solution of chitosan is prepared by coagulating an emulsion of an acidic aqueous solution of chitosan with an organic solvent alone or an organic solvent containing a base. The inventors have found that it is possible to obtain fine spherical chitosan fine particles having a diameter of about 0.1 to 50 μm and completed the present invention. That is, the present invention is to inject a W / O emulsion of chitosan acidic aqueous solution into an organic solvent alone or an organic solvent containing a base,
The present invention provides a method for producing spherical chitosan fine particles, which comprises solidifying and precipitating spherical chitosan fine particles.

The chitosan used in the present invention is not particularly limited, but in consideration of the solubility in an acidic aqueous solution, chitosan having a deacetylation degree of 80% or more is preferably used. When the degree of deacetylation is low, the solubility in an acidic aqueous solution is poor, which is not preferable. The molecular weight of chitosan is not particularly limited, but considering the strength of fine particles, the weight average molecular weight is 1 × 10 ³ to 1 × 10 ⁶
Chitosan is preferred. The acid used as the acidic aqueous solution is an inorganic acid such as hydrochloric acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, lactic acid, citric acid, tartaric acid, succinic acid, malic acid, oxalic acid, glycolic acid, dichloroacetic acid, trifluoroacetic acid. Examples of such organic acids include tartaric acid, succinic acid, malic acid, and glycolic acid from the viewpoint of solubility / safety / odor.

As a method for preparing an acidic aqueous solution of chitosan, 50
A general method is to slowly add and dissolve chitosan in an acidic aqueous solution of the above acid heated to ˜70 ° C. with stirring. The concentration of the acid at this time is not particularly limited as long as chitosan can be dissolved therein. The concentration of chitosan is not particularly limited, but 1 to 10% by weight is desirable in terms of viscosity.

In the present invention, the emulsifying agent used for emulsification includes sorbitan monostearate, sorbitan monooleate, sorbitan monolaurate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monooleate and polyoxyethylene sorbitan. Nonionic surfactants such as monolaurate, polyoxyethylene lauryl alcohol ether and polyoxyethylene cetyl alcohol ether are preferred. These emulsifiers may be used alone or in combination of two or more.

Specific examples of the hydrophobic solvent used for dissolving the emulsifier include hydrocarbons such as hexane and cyclohexane, aromatics such as toluene and benzene, and ethers such as petroleum ether and diethyl ether. Kind,
Examples thereof include halogenated hydrocarbons such as chloroform and carbon tetrachloride. The concentration of the emulsifier contained in the hydrophobic solvent is appropriately in the range of 0.1 to 10.0% by weight, preferably 0.5 to 5.0% by weight.

W / of the chitosan acidic aqueous solution in the present invention
The O emulsion is prepared by adding an emulsifier-containing hydrophobic solvent to the chitosan acidic aqueous solution and performing emulsification by mechanical stirring using an emulsifying device. Examples of the emulsifying device include a homogenizer, a high-pressure homogenizer, a milder, a homomixer, a touch mixer, an ultrasonic emulsifying device, a nanomizer system, and a glass film emulsifying device. The mixing ratio of the chitosan acidic aqueous solution / the emulsifier-containing hydrophobic solvent at the time of emulsification is preferably 9/1 to 1/9 by volume ratio, particularly preferably 7/3 to 3/7.

In the present invention, the W / O emulsion of the chitosan acidic aqueous solution prepared as described above is poured into an organic solvent alone or an organic solvent containing a base to coagulate and precipitate while maintaining the spherical shape. As a coagulation liquid for coagulating and depositing a chitosan emulsion, in the case of an organic solvent alone, methanol, ethanol, propanol, isopropanol, butanol, polar solvents such as acetone, acetonitrile, tetrahydrofuran, dioxane, ethyl acetate, etc., Non-polar solvents such as cyclohexane and hexane are preferably used.

When the coagulating liquid is an organic solvent containing a base,
As the organic solvent, alcohols such as methanol, ethanol, propanol, isopropanol and butanol, polar solvents such as acetone, acetonitrile, tetrahydrofuran, dioxane and ethyl acetate, non-polar solvents such as cyclohexane and hexane, etc. are used. The following polar solvents such as alcohols, acetone, acetonitrile, tetrahydrofuran, dioxane and ethyl acetate are preferable. As the base, amines such as ammonia, methylamine, ethylamine, propylamine, butylamine, isobutylamine, hexylamine, octylamine, amino-modified silicone, ethylenediamine, propylenediamine, butylenediamine, sodium hydroxide, potassium hydroxide, water. Examples thereof include alkaline substances such as calcium oxide, sodium hydroxide, potassium hydroxide, butylamine, hexylamine, and octylamine are preferable, and butylamine, hexylamine, and octylamine are more preferable because spherical spherical chitosan fine particles are obtained. As.

The amount of the coagulating liquid in this case varies depending on the type of the coagulating liquid and the like, but is usually 2 to 50 times the volume of the emulsion. When a W / O emulsion containing chitosan is dropped into such a coagulating liquid while stirring, chitosan coagulates and precipitates as spherical particles. Spherical chitosan particles are collected by filtration, centrifugation, or the like, sufficiently washed with alcohol, and then dried to obtain spherical chitosan fine particles.

[0017]

EXAMPLES Next, the present invention will be described in more detail by way of examples, but the present invention is not limited to the following examples.

Example 1 78 g of commercially available chitosan (SK-10 manufactured by Koyo Chemical Co., Ltd., deacetylation degree: 85 to 88%, weight average molecular weight: 13000) was added to water.
Dispersed in 892 g, 30 g of acetic acid was added and dissolved at 60 ° C. with stirring to prepare a 7.8 wt% chitosan / acetic acid aqueous solution.
Add sorbitan monolaurate to this acidic chitosan solution.
A 2.0 wt% cyclohexane solution was mixed at a ratio of 4/6 (volume ratio), and high-speed stirring (8000 rpm) was performed with a homogenizer to obtain a W / O emulsion. Next, 20 ml of the obtained emulsion is added dropwise to 100 ml of ethanol with stirring for coagulation treatment, and the coagulated product is treated with stainless steel wire mesh (32
Chitosan microparticles were obtained by filtering and collecting with 5 mesh and opening 0.044 mm) and vacuum drying. Table 1 shows the average particle diameter and the like of the obtained chitosan fine particles. An electron micrograph of the obtained spherical chitosan fine particles is shown in FIG. 1, and an electron micrograph of only one fine particle in FIG. 1 is enlarged in FIG.
An electron micrograph of a fractured surface of one particle in FIG. 1 is shown in FIG.
Shown in.

Example 2 70 g of commercially available chitosan (SK-10) was dispersed in 880 g of water, 50 g of acetic acid was added, and the mixture was dissolved at 60 ° C. with stirring to obtain 7.0% by weight.
An aqueous chitosan / acetic acid solution was prepared. A 1.0 wt% n-hexane solution of sorbitan monostearate was mixed with this chitosan acidic aqueous solution at a ratio of 4/6 (volume ratio), and high speed stirring (15000 rpm) was performed with a homogenizer to obtain a W / O emulsion. Next, add 20 ml of the obtained emulsion to 1
Chitosan fine particles were obtained by dropping the mixture into 100 ml of a / 10 N butylamine / acetone solution with stirring for coagulation treatment, collecting the coagulated product with a stainless steel wire net, collecting and vacuum drying. Table 1 shows the average particle size of the obtained chitosan fine particles.
It was shown to.

Example 3 78 g of commercially available chitosan (SK-10) was dispersed in 872 g of water, 50 g of tartaric acid was added, and the mixture was dissolved at 60 ° C. with stirring to prepare a 7.8 wt% chitosan / tartaric acid aqueous solution. A 2.0 wt% toluene solution of sorbitan monolaurate was mixed with this chitosan acidic aqueous solution at a ratio of 1/1 (volume ratio), and high speed stirring (10000 rpm) was performed with a homogenizer to obtain a W / O emulsion. Next, add 20 ml of the obtained emulsion to 1
Chitosan fine particles were obtained by dropping the mixture into 100 ml of a / 10 N butylamine / acetone solution with stirring for coagulation treatment, collecting the coagulated product with a stainless steel wire net, collecting and vacuum drying. Table 1 shows the average particle size of the obtained chitosan fine particles.
It was shown to.

Example 4 70 g of commercially available chitosan (SK-10) was dispersed in 900 g of water, 30 g of glycolic acid was added, and the mixture was dissolved at 60 ° C. with stirring, and 7.
A 0 wt% chitosan / glycolic acid aqueous solution was prepared. Add sorbitan monostearate to this chitosan acidic aqueous solution.
1.0 / 6 wt% cyclohexane solution in a ratio of 4/6 (volume ratio)
And mixed by high speed stirring (10000 rpm) with a homogenizer to obtain a W / O emulsion. Next, 20 ml of the obtained emulsion was added dropwise to 100 ml of a 1/10 N potassium hydroxide / ethanol solution with stirring to carry out a coagulation treatment, and the coagulated product was filtered through a stainless steel wire net, collected and vacuum dried to obtain chitosan. Fine particles were obtained. Table 1 shows the average particle diameter and the like of the obtained chitosan fine particles.

Comparative Example 1 70 g of commercially available chitosan (SK-10) was dispersed in 900 g of water, 30 g of acetic acid was added, and the mixture was dissolved at 60 ° C. with stirring to obtain 7.0% by weight.
An aqueous chitosan / acetic acid solution was prepared. A 2.0 wt% cyclohexane solution of sorbitan monolaurate was mixed with this chitosan acidic aqueous solution at a ratio of 5/5 (volume ratio), and high speed stirring (10000 rpm) was performed with a homogenizer to obtain a W / O emulsion. The obtained emulsion was dropped into a 1N aqueous sodium hydroxide solution under vigorous stirring for coagulation treatment, and the coagulated product was collected by stainless steel wire mesh filtration and vacuum dried. I could not do it.

Comparative Example 2 70 g of commercially available chitosan (SK-10) was dispersed in 880 g of water, 50 g of acetic acid was added, and the mixture was dissolved at 60 ° C. with stirring to obtain 7.0% by weight.
An aqueous chitosan / acetic acid solution was prepared. A 2.0 wt% cyclohexane solution of sorbitan monolaurate was mixed with this chitosan acidic aqueous solution at a ratio of 5/5 (volume ratio), and the mixture was stirred with a homogenizer to prepare a W / O emulsion. The obtained emulsion was spray-dried in a high temperature atmosphere to coagulate it. A coagulated product with an average particle size of about 40 μm was obtained, but it became amorphous chitosan fine particles.

Comparative Example 3 78 g of commercially available chitosan (SK-10) was dispersed in 872 g of water, 50 g of acetic acid was added, and the mixture was dissolved at 60 ° C. with stirring to give 7.8% by weight.
An aqueous chitosan / acetic acid solution was prepared. The chitosan acidic aqueous solution was dropped into the 1N sodium hydroxide aqueous solution by a constant amount under a constant pressure. The obtained coagulated product was collected by stainless steel wire mesh filtration, and dried in vacuum to be spherical, but it was chitosan particles having an average particle size of about 200 μm.

Table 1 shows the manufacturing conditions of Examples 1 to 4 and Comparative Examples 1 to 3 and the morphology of the obtained fine particles.

[0026]

[Table 1]

[0027]

The chitosan fine particles obtained according to the present invention have an average particle size of about 0.1 to 50 μm and have a substantially spherical appearance as shown in FIGS. Further, as shown in FIG. 3, it can be confirmed to have porosity.
Since the chitosan fine particles obtained by the present invention are fine, spherical and porous as described above, they are suitable as a catalyst carrier, a packing material for chromatography, and a powder for cosmetics which is excellent in touch and the like.

[Brief description of drawings]

FIG. 1 is an electron micrograph showing the particle structure of spherical chitosan fine particles obtained in Example 1.

FIG. 2 is an electron micrograph showing a particle structure in which only one particle in FIG. 1 is enlarged.

FIG. 3 is an electron micrograph showing a structure of a split cross section of one fine particle in FIG.

Claims (2)

[Claims] 1. A method for producing spherical chitosan fine particles, which comprises pouring a W / O emulsion of an acidic aqueous chitosan solution into an organic solvent alone or an organic solvent containing a base to coagulate and deposit the spherical chitosan fine particles. 2. The method for producing spherical chitosan fine particles according to claim 1, wherein the organic solvent is a polar solvent.