JP2794439B2 - Method for controlling micropore size of cellulosic material - Google Patents

Description

The present invention relates to a method for controlling the size of micropores in a cellulosic material. Among cellulose materials having micropores, porous cellulose particles are useful as chromatographic agents, cosmetic raw materials, and the like.

[Conventional technology and its problems]

Cellulose is a naturally occurring macromolecule,
It has micropores as a material.

Among cellulose materials having micropores, porous particles are widely used as chromatographic agents such as gel filtration, ion exchange, and affinity, and as raw materials for cosmetics.

When the porous cellulose particles are used as a chromatographic agent, the fine pores, that is, the pore size, and the volume ratio (porosity) of the pores greatly affect the performance as a chromatographic agent. For example, a gel filtration agent is separated by a sieve effect depending on the size of a molecule. Naturally, the influence of the pore of the gel is large, and a pore size corresponding to the molecule to be separated is required. It is also known that even in the case of ion exchange affinity, the separation performance and processing performance differ depending on the mode of the pore.

For this purpose, various methods for adjusting pores of cellulose particles have been proposed.

For example, JP-A-56-24429, JP-A-56-24430,
JP-A-57-38801 is an example.

The method of dissolving cellulose triacetate in an organic solvent,
Further, a higher alcohol or the like is added as a diluent. The cellulose triacetate solution is stirred and dispersed in an aqueous dispersion, and the solvent is distilled off to obtain cellulose triacetate spherical particles. Then, it is a method of obtaining cellulose particles by saponifying it, and it is said that the pores are adjusted by the amount of diluent. According to the method (1), a large amount of diluent is required to obtain particles having a large pore size, so that much labor is required for washing and collecting the diluent.

The method is to dissolve a mixture of crystalline cellulose triacetate having a certain degree of polymerization and cellulose triacetate having an amorphous part in an organic solvent, stir and disperse in an aqueous dispersion, and distill off the solvent. Obtain cellulose triacetate spherical particles. Then, this is a method of obtaining cellulose particles by saponification, and the size of pores is adjusted by changing the mixing ratio of two kinds of cellulose triacetate. This method requires a special crystalline cellulose having a certain degree of polymerization, but such cellulose is generally produced by acid hydrolysis of natural cellulose and is very expensive compared to natural cellulose.

Is to add an acid or an alkali to a solution of a cellulose organic acid ester, and then separate the mixture into an aqueous dispersion by stirring, and distill off the solvent to obtain cellulose ester spherical particles. Then, this is a method of obtaining cellulose particles by saponification, and the size of pores is adjusted by adjusting the amount of acid or alkali added. However, the pores of the cellulose particles obtained by this method are relatively small pores, and cannot be applied to a method for obtaining a pore corresponding to the size of a protein molecule having a molecular weight of tens of thousands or more in use.

[Problems to be solved by the invention]

As described above, there have been various problems in the conventional methods for controlling the size of porous cellulose particles and pores.
They were also applied only at the stage of forming the cellulose particles, and the pores could not be adjusted after particle formation.

The present invention is intended to solve the problems of the prior art and to provide a method for adjusting the size of pores in order to obtain a cellulose material having micropores, particularly a porous cellulose material useful as a chromatographic agent and the like. .

As a result of examining the action of various liquids on cellulose, the present inventors have found that, by treating the cellulose material with a liquid that hardly dissolves or only dissolves a small amount to swell the cellulose, finally the porous cellulose material The present inventors have found that the pores change, and based on this finding, have further studied and reached the present invention.

[Means for solving the problem]

 The present invention has the following configurations (1) to (4).

(1) Cellulose characterized by treating a cellulose material with one or more compounds selected from thiocyanate or a combination of sodium hydroxide and sodium borohalide, which is a liquid treating agent capable of swelling the cellulose material. How to control the micropore size of a material.

(2) treating the porous spherical cellulose particles with one or more compounds selected from a combination of thiocyanate or a combination of sodium hydroxide and sodium borohalide, which is a liquid treating agent capable of swelling the cellulose material. A method for adjusting the fine pore size of the characteristic porous spherical cellulose particles.

(3) The cellulose material is treated with one or more compounds selected from the group consisting of copper ammonia, zinc chloride, cadoxene and hydrazine, which are liquid treating agents capable of swelling the cellulose material. How to adjust the hole size.

(4) Porous spherical cellulose particles (hereinafter “intermediate portion”)
Is the same as (3)) a method for adjusting the micropore size of the porous cellulose particles.

That is, the present invention is a cellulose material for cellulose,
After swelling by immersing in a swelling liquid treatment agent,
In this method, the pore size of the cellulose material is adjusted by removing the liquid agent by washing or the like.

The cellulosic material used in the method of the present invention can be carried out in any form such as fibrous, granular, spherical, massive, etc., but when used for the purpose of a chromatographic agent, spherical particles are preferred.
Further, the present invention is also applicable to the film-form cellulose of the present invention. As a method for producing cellulose particles used in the present invention, for example, various proposed methods such as JP-A-61-241337, JP-A-55-44312, JP-A-53-7759, and JP-A-51-5361 can be used. Is not particularly limited.

Liquid treating agents used in the method of the present invention include those used as aqueous solutions, such as thiocyanates or inorganic compounds such as sodium hydroxide and sodium borohalide.

In addition, examples of similar inorganic compounds include copper ammonia, zinc chloride, cadoxene and hydrazine.

Each can be used alone or in combination.

When the treatment of the method of the present invention is performed with an aqueous solution, the concentration of the solution is selected depending on the desired pore size. In general, when used at a high concentration, a large-sized pore is obtained, and when used at a low concentration, a change in the pore size from the pore before treatment is small. The concentration can be generally used in the range of 0.1% by weight or more and the solubility of cellulose or less, but is preferably 1 to 60% by weight.

Soaking or swelling time is not particularly limited,
If the treatment time is too short, the treatment effect becomes insufficient, and if the treatment time is unnecessarily long, the cellulose is deteriorated or deteriorated. Therefore, usually, 1 to 24 hours is appropriate. The same applies to the temperature, preferably 5 to 100 ° C.

However, depending on the type of the liquid treating agent, the dissolving effect may be significantly increased under certain conditions, and such conditions must be avoided. For example, in an aqueous solution of calcium thiocyanate, if the concentration is 50% or more and the temperature is 90 ° C or more, there is a possibility of dissolution, so the concentration is preferably less than 50% and the temperature is less than 80 ° C.

The ratio of the cellulose to the treatment solution may be within a range in which the cellulose can be sufficiently contacted with the solution. However, since the use of excess solution is lost, the weight of the treatment solution is preferably based on 1 part by weight of the cellulose. Is 100 times or less, preferably 1 to 50
It is twice.

The treatment with the liquid treating agent is generally carried out with stirring in a stirring tank, but it is also possible to carry out the treatment with standing or filling a column or the like.

After the treatment with the liquid treating agent is completed, the cellulose to be treated is washed and replaced with an inactive liquid. As the inactive liquid, water, alcohols, acetone or a mixture thereof is usually used. Washing and replacement can be performed by removing the treatment liquid by filtration or the like and then adding an inactive liquid, or by mixing the treatment liquid with a large amount of an inactive liquid without separating the treatment liquid.

〔Example〕

Examples are shown below, but the method of the present invention is not limited to the methods described in these examples. The pores of the cellulose particles obtained in the following examples were evaluated by measuring the exclusion limit molecular weight by liquid chromatography. The measuring method is described in the comparative test example described later.

Example 1 According to Example 1 described in JP-A-56-24429, 320 g of cellulose triacetate and 300 ml of n-octanol were dissolved in 4000 ml of methylene chloride, and this solution was dispersed in a 4% aqueous solution of gelatin. Is evaporated off. The obtained particles were saponified with an alkali and classified to obtain spherical cellulose particles having a diameter of 40 to 100 μm in a water-swelled state. The exclusion limit molecular weight of the cellulose particles was 4,000 for dextran.

The obtained water-swelled spherical cellulose was filtered by suction, and 100 g (equivalent to 42 g when dried) of the wet cellulose was stirred in 50 ml of a 30% by weight aqueous solution of ammonium thiocyanate at 50 ° C. for 16 hours. After cooling to room temperature, the mixture was filtered and washed to obtain spherical cellulose particles. The exclusion limit molecular weight of the cellulose particles was 25,000 for dextran. This exclusion limit molecular weight corresponds to the case where about three times as much n-octal is used according to the examples of the above-mentioned publication.

Example 2 According to Example 3 of JP-A-55-44312 and the like, a diameter of 120 to
250 micron cellulose particles were obtained. The exclusion limit molecular weight of this cellulose particle is 300 with polyethylene glycol.
It was 10,000.

The particles suspended in water are suction filtered. In the wet state
500 g of a 10% by weight aqueous sodium hydroxide solution containing 0.1 g of sodium borohydride to prevent oxidation of 100 g of particles
and stirred at 40 ° C. for 5 hours. After cooling to room temperature, the supernatant is removed by decantation. Then, 500 ml of water is added, and after stirring, decantation is performed. This operation was further performed three times, followed by suction filtration, and washing with water until the filtrate became neutral. The exclusion limit molecular weight of the obtained cellulose particles was 1,000,000 with polyethylene glycol.

Comparative Test Example Cellulose particles obtained by the method of the present invention 22 mm in diameter,
Pack into a chromatography column of 500 mm length (column volume 190 ml). A pump was connected to the column, and the eluate (0.05 mol to which 0.1 mol of potassium chloride was added, a phosphate buffer solution,
pH 7.2) at a flow rate of 40 ml / hr to 600 ml. Then, 0.1 ml of an eluate solution (5 mg / 1 ml) of a marker of a known molecular weight (polyethylene glycol or dextran) was added to the column,
The eluate is flowed at a flow rate of 40 ml / hr. The elution volume of the marker is measured with a detector (differential refractometer) connected to the column outlet. Column volume is Vt (ml), marker elution volume is Ve
(Ml), Ve / Vt (%) of each marker is plotted against the logarithmic value of the molecular weight of the marker, and the exclusion limit molecular weight is determined from this graph (calibration curve). The exclusion limit molecular weight is a limit molecular weight of a porous particle in which a molecule having a higher molecular weight cannot penetrate into the particle. Table 1 shows the thus-excluded molecular weights of the respective particles.

FIG. 1 shows the Ve / Vt (%) of a marker of a known molecular weight (dextran in Example 1, polyethylene glycol in Example 2) measured in the comparative test on the horizontal axis, and the molecular weight of the marker on the logarithmic scale on the vertical axis. It is a graph plotted. Ve / Vt is about 40 when the molecular weight of the marker increases
%, And becomes a vertical straight line. This is because the marker molecules cannot penetrate into the pores of the cellulose and only pass through the voids between the particles. In general, as the molecular weight of a molecule that can penetrate inside the pore decreases, the elution to penetrate into many particles becomes slow, and the molecule becomes a straight line or a curved line with a slope. The molecular weight at the intersection of these two straight lines or curves (note: break point in the figure) is the exclusion limit molecular weight.

〔The invention's effect〕

As shown in Table 1, in Example 1, the exclusion limit molecular weight before the treatment by the method of the present invention was 4000, whereas the molecular weight after treatment by the method of the present invention was 25,000. This is disclosed in
According to Example 1 of Japanese Patent No. 4429, this cannot be achieved unless three times as much diluent is used. In the method of JP-A-57-38801, the exclusion limit molecular weight is limited to several thousand, but it is clear that 10,000 or more can be easily achieved by the method of the present invention.

Further, as described in JP-A-55-44312, it is difficult to dissolve cellulose at a high concentration in a method of directly dissolving cellulose into particles, so that the resulting cellulose particles have a very large pore. You can only get things. As shown in Example 2, the method of the present invention can also modify such a large pore cellulose particle to one having an appropriately sized pore.

As shown in the above description, the method of the present invention can easily adjust the pores of the cellulose material, particularly the cellulose particles, obtained by various methods. Very useful.

[Brief description of the drawings]

FIG. 1 shows the molecular weight-Ve in each embodiment of the method of the present invention.
Shows the / Vt (%) calibration line. In each figure, the solid line is after processing and the broken line is before processing.

Claims (4)

(57) [Claims] (1) treating a cellulose material with one or more compounds selected from thiocyanate, which is a liquid treating agent capable of swelling the cellulose material, or a combination of sodium hydroxide and sodium borohalide; Of controlling the size of micropores in a cellulosic material. 2. Treating the porous spherical cellulose particles with one or more compounds selected from thiocyanate or a combination of sodium hydroxide and sodium borohalide, which is a liquid treating agent capable of swelling the cellulose material. A method for controlling the fine pore size of porous spherical cellulose particles, characterized by the following. 3. A method of treating a cellulose material with one or more compounds selected from the group consisting of copper ammonia, zinc chloride, cadoxene and hydrazine, which are liquid treating agents capable of swelling the cellulose material. How to control the micropore size. 4. A method for adjusting the fine pore size of porous spherical cellulose particles (hereinafter the "intermediate portion" is the same as in (3)).