JPH04275303A - Production of fine crosslinked cellulose particle - Google Patents

Abstract

PURPOSE:To provide a method for producing fine crosslinked cellulose particles having a small excluded limit mol.wt. and high theoretical stage number characteristics and suitable as a filler for cellulosic gel filtration. CONSTITUTION:The method for producing fine crosslinked cellulose particles having an excluded limit mol.wt. of approximately. <=3000 comprises swelling fine non-crosslinked cellulose particles in the presence of a basic compound in a water-containing medium, separating the swollen particles from the water- containing medium, subjecting the separated particles to a crosslinking reaction in the presence of a basic compound in a hydrophilic aprotic organic solvent, separating the produced fine crosslinked cellulose particles from the mother solution, and subsequently washing the separated fine particles with water.

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 micro crosslinked cellulose particles. More specifically, the present invention relates to a method for producing micro crosslinked cellulose particles, which have a small exclusion limit molecular weight and a high number of theoretical plates, and are suitably used as a cellulose-based gel filtration filler.

0002

BACKGROUND OF THE INVENTION In recent years, granular materials of cellulose or its various derivatives have come to be used as chromatography materials.

[0003] Cellulose carriers used as packing materials for chromatography are designed in terms of particle size, pore size inside the carrier, etc. depending on the purpose of separation.

[0004] Journal of the Chemical Society of Japan 1984 No. 5, 72
On pages 2 to 727, there is a research report on the production of porous cellulose spherical particles from cellulose organic acid esters and the properties of the particles.

[0005] Furthermore, JP-A-57-38801 similarly discloses a method for producing porous cellulose spherical particles from cellulose organic acid ester.

These cellulose carriers for chromatography have been shown to be useful in separating proteins with relatively large molecular weights.

However, the porous cellulose particles produced by these methods have a problem in that the pore size inside the cellulose carrier becomes smaller and the amount of pores also becomes smaller, resulting in lower separation accuracy.

In recent years, ion exchange resins, Gel filtration agents and the like are used, but it is difficult to fractionate substances with a molecular weight in the range of 500 to 1000, such as trisaccharides or more of oligosaccharides, by gel filtration with good separation performance.

[0009] Journal of the Chemical Society of Japan 1981 No. 12, 1
A research report on the production of cellulose spherical gel and its performance in gel chromatography is published on pages 883-1889.

[0010] This report examines the crosslinking effect on cellulose, and reports as a fact that when spherical cellulose is subjected to a crosslinking reaction using epichlorohydrin, the pore size does not become smaller than that of uncrosslinked spherical cellulose. The same report considers that this phenomenon is caused by the destruction of hydrogen bonds due to the crosslinking reaction, which actually enlarges the network structure of cellulose and increases the pore size. That is, it was conventionally understood that cellulose particles with a molecular weight of several thousand or less and a small pore size were difficult to obtain even by crosslinking.

[0011]

SUMMARY OF THE INVENTION An object of the present invention is to provide a method for producing micro crosslinked cellulose particles having a small exclusion limit molecular weight.

Further objects and advantages of the invention will become apparent from the following description.

[0013]

According to the present invention, the above objects and advantages of the present invention are achieved by:

(1) (a) consists essentially of a type II cellulose crystalline phase and a cellulose amorphous phase, (b) consists essentially of spherical or oblate particles with an average particle diameter of 500 μm or less, and ( c) Prepare minute non-crosslinked cellulose particles whose exclusion limit molecular weight by polyethylene glycol is in the range of about 1,000 to about 10,000, (2) Prepare the minute non-crosslinked cellulose particles with a basic compound in a water-containing medium. (3) separating the swollen particles from the aqueous medium; (4) subjecting the separated particles to a crosslinking reaction in a hydrophilic aprotic organic solvent in the presence of a basic compound; , and (5) the generated fine crosslinked cellulose particles are separated from the mother liquor and then washed with water until the exclusion limit molecular weight is approximately 3.
This is achieved by a method for producing micro crosslinked cellulose particles having a small exclusion limit molecular weight, which is characterized by producing micro crosslinked cellulose particles having a molecular weight of 1,000 or less.

According to the method of the present invention, the first step (
Fine non-crosslinked cellulose particles are prepared in step (1)), subjected to swelling treatment in the second step (step (2)), and
In the step (step (3)), the swelling-treated particles are separated from the medium, subjected to a crosslinking reaction in the fourth step (step (4)), and the crosslinking reaction is performed in the fifth step (step (5)). The cellulose particles are separated from the mother liquor and then washed with water.

The fine non-crosslinked cellulose particles prepared in the first step can be obtained, for example, by the following method.

(1) Prepare an alkaline polymer aqueous solution containing cellulose xanthate and another water-soluble polymer compound different from it (hereinafter referred to as the first water-soluble polymer compound),

(2) Mixing the above alkaline polymer aqueous solution and a water-soluble anionic polymer compound (hereinafter referred to as a second water-soluble anionic polymer compound) to produce a fine particle dispersion of the alkaline polymer aqueous solution. Seshime,

[0019]
(3) (i) By heating the dispersion produced in step (2) above or mixing the dispersion with a coagulant for cellulose xanthate, the cellulose xanthate in the dispersion is converted into the first Either it is coagulated as microparticles containing a water-soluble polymer compound, and then neutralized with acid to regenerate the cellulose to produce microparticles containing cellulose;

(ii) coagulating and neutralizing the dispersion produced in step (2) above with an acid to regenerate cellulose and produce fine particles containing cellulose;

(4) Solidification and/or coagulation in step (3)(i) above
or during neutralization, during coagulation and neutralization in step (3) (ii), or in each step thereafter, removing the first water-soluble polymer compound from the fine particles generated in each step;

(5) Non-crosslinked cellulose particles having an exclusion limit molecular weight in the range of about 1000 to about 10,000 can be obtained by dehydrating, pickling, water washing and drying.

According to the present invention, in the second step, the microscopic non-crosslinked cellulose particles are then swollen in an aqueous medium in the presence of a basic compound.

As the water-containing medium, methanol, ethanol, acetone, etc. can be used as a mixture with water or water alone. As the basic compound, for example, sodium hydroxide and potassium hydroxide are preferably used.

The concentration of the basic compound in the aqueous medium is 5% to 20% by weight, and the temperature is appropriately selected within the range of 5 to 30° C. so that the spherical shape of the cellulose particles is maintained.

[0026] Next, in the third step, the particles subjected to the swelling treatment are separated from the aqueous medium containing the basic compound.

Separation from the water-containing medium is carried out by using a glass filter, washing with water, and then drying. Drying is carried out, for example, at a temperature of 60 to 80°C for a long time of 20 hours or more.

[0028] After the above-mentioned washing with water, the solvent may be replaced with a hydrophilic aprotic organic solvent used in the fourth step. The non-crosslinked cellulose particles separated from the water-containing medium in the fourth step are then subjected to a crosslinking reaction in a hydrophilic aprotic organic solvent in the presence of a basic compound.

As the hydrophilic aprotic organic solvent, for example, dimethyl sulfoxide, acetone, methyl ethyl ketone, etc. are suitably used alone or as a mixture.

As the basic compound, for example, alkali hydroxides such as sodium hydroxide and potassium hydroxide are preferably used. It is preferable to use the alkali hydroxide dissolved in a small amount of water.

As the crosslinking agent, halohydrins such as epichlorohydrin and dichlorohydrin are advantageously used.

In the fourth step, the fine non-crosslinked cellulose particles are first dispersed in a hydrophilic aprotic organic solvent. The crosslinking agent can be contained in the aprotic organic solvent in advance, or can be added after dispersing the non-crosslinked cellulose particles.

Preferably, 0.5 to 50 parts by weight of the aprotic organic solvent is used, more preferably 3 to 20 parts by weight, per 1 part by weight of the fine non-crosslinked cellulose particles.

The crosslinking agent is preferably used in an amount of 1 to 50% by weight, more preferably 5 to 4% by weight based on the aprotic solvent.
0% by weight is used.

After the non-crosslinked cellulose particles have been sufficiently swollen by penetration of the aprotic organic solvent, the basic compound is added, preferably as an aqueous solution.

[0036] The basic compound preferably has a ratio of 2 to 2
~50% by weight, more preferably 5-30% by weight
It is preferable to use it as an aqueous solution.

The aqueous solution of the basic compound is preferably used in an amount of 0.1 to 6 parts by weight, more preferably 0.5 to 5 parts by weight, per 1 part by weight of the fine non-crosslinked cellulose particles. The initial temperature of the crosslinking reaction is preferably 10 to 30°C, and after the aqueous solution of the basic compound has sufficiently penetrated into the particles swollen with a hydrophilic aprotic organic solvent, the temperature is gradually raised to 50°C. The crosslinking reaction is preferably carried out for 4 to 8 hours.

Next, according to the method of the present invention, in the fifth step, the produced fine crosslinked cellulose particles are separated from the mother liquor and washed with water.

Thus, according to the present invention, as described above, micro crosslinked cellulose particles having an exclusion limit molecular weight of about 3,000 or less are provided.

[0040]

[Examples] The present invention will be explained in detail with reference to Examples below. Before that, methods for measuring various characteristic values in this specification will be described.

Particle Size Measurement Method Approximately 0.1 g of a sample is collected, poured into 25 ml of pure water, stirred and dispersed, and measured using a light transmission type particle size distribution analyzer. The average particle diameter was calculated on a volume basis.

Exclusion Limit Molecular Weight/Theoretical Plate Number Fine cellulose particles were each packed into a 10 mmφ x 30 cm resin column using water as a filling liquid at a flow rate of 4.0 ml/min for 60 minutes. Next, using each packed column as a separation column, the relationship between elution time and molecular weight is blotted using standard polyethylene glycol of known molecular weight under the following analysis conditions, and the exclusion limit molecular weight is determined as the molecular weight of polyethylene glycol at the bending point of the curve. I asked for it.

The number of theoretical plates was calculated from the following formula by measuring the peak position and peak width of ethylene glycol in units of volume.

[0044]

[Formula 1]

N: number of theoretical plates, Ve: elution position of ethylene glycol (ml), W:
Elution width of ethylene glycol (ml).

The analysis conditions are as follows. 1. Pump Waters 6000A type, 2
．． Eluent: pure water, 3. Flow rate 1.0ml/min, 4. Temperature: room temperature, 5. Detector PI detector.

Example 1 (1). 500g of pulp made from coniferous wood was heated at 20℃, 18
Immersed in 20 liters of wt% caustic soda solution for 1 hour, 2.8
Squeezed twice. The mixture was pulverized for 1 hour while increasing the temperature from 25°C to 50°C for aging, and then 35% by weight of carbon disulfide (175 g) was added to the cellulose and sulfurized at 25°C for 1 hour to obtain cellulose xanthate. . The xanthate was dissolved in an aqueous solution of caustic soda to obtain viscose. The viscose had a cellulose concentration of 9.3% by weight, a caustic soda concentration of 5.9% by weight, and a viscosity of 6200 centipoise.

(2). 3300g of 10.8% sodium polyacrylate aqueous solution (molecular weight 100,000) in a 5L plastic container
, 132 g of calcium carbonate and 40 g of calcium hydroxide
g and stirred with a homomixer. After dispersion, liquid temperature 25℃
868 g of the above viscose liquid was added and stirred at 400 rpm for 10 minutes using a lab stirrer. After producing viscose fine particles, the liquid temperature was raised from 25°C to 75°C in 25 minutes while stirring, and then the temperature was increased to 75°C.
The viscose microparticles were solidified by maintaining the temperature for 15 minutes. The coagulated viscose particles were separated from the mother liquor using a G4 type glass filter, and then neutralized with 5% by weight hydrochloric acid to obtain cellulose particles, which were washed with a large excess of water and then dried in a ventilation dryer at 105° C. for 2 hours. The obtained cellulose particles are
Exclusion limit molecular weight with polyethylene glycol is 820
It was 0.

(3). Next, the cellulose particles 200
g was swollen in a 10% by weight aqueous sodium hydroxide solution at 20°C, separated from the mother liquor using a glass filter, washed with water, and then dried at 80°C for 24 hours.

(4). Next, the cellulose particles 100
After putting 300 g of dimethyl sulfoxide and 105 g of epichlorohydrin into a 1-liter flask and stirring to sufficiently swell the cellulose particles, 276 g of a caustic soda aqueous solution in which 76 g of caustic soda was dissolved was gradually added little by little. Addition of the caustic soda aqueous solution was carried out over 1 hour while adjusting the liquid temperature to 20°C.

[0051] Next, the liquid temperature was raised to 50°C in 1 hour, and thereafter the crosslinking reaction was completed while being controlled at 50°C. The produced fine crosslinked cellulose particles were separated from the mother liquor by a glass filter, and then neutralized with 1% by weight hydrochloric acid.
Washed with large excess of water.

The crosslinked cellulose particles obtained had an average particle diameter of 30 μm and an exclusion limit molecular weight of 1000 with polyethylene glycol.

[0053] These particles were packed into a column with an inner diameter of 10 mmφ x 30 cm, and the number of theoretical plates for ethylene glycol was measured, and it was found to be 3000 plates/30 cm.

Example 2 (1). 2,400 g of a 12.0% sodium polyacrylate aqueous solution (molecular weight: 50,000) and 28 g of calcium carbonate were placed in a 5-liter plastic container and stirred with a homomixer.

After dispersion, at a liquid temperature of 25° C., 1600 g of the same viscose liquid as used in Example 1 was added and stirred at 150 rpm using a lab stirrer for 10 minutes. After producing viscose fine particles, the liquid temperature was raised from 25°C to 75°C in 25 minutes while stirring,
The temperature was maintained at 75° C. for 30 minutes to solidify the viscose microparticles. The coagulated viscose particles were separated from the mother liquor using a G1 glass filter, neutralized with 5% by weight hydrochloric acid to obtain cellulose particles, washed with a large excess of water, and then dried in a ventilation dryer at 105° C. for 5 hours.

The cellulose particles obtained had an exclusion limit molecular weight of 3,500 with polyethylene glycol.

(2). Next, the cellulose particles 200
g was swollen in a 10% by weight aqueous sodium hydroxide solution at 15°C, separated from the mother liquor using a glass filter, washed with water, and then dried at 60°C for 20 hours.

(3). Then 100g of the cellulose particles
, 300 g of dimethyl sulfoxide and 105 g of epichlorohydrin were placed in a 1 liter flask, and after stirring to sufficiently swell the cellulose particles, 360 g of an aqueous solution of caustic soda in which 60 g of caustic soda was dissolved was gradually added little by little. Addition of the caustic soda aqueous solution was carried out over 1 hour while adjusting the liquid temperature to 20°C.

[0059] Next, the liquid temperature was raised to 50°C in 1 hour,
Thereafter, the crosslinking reaction was completed while controlling the temperature to 50°C. The produced fine crosslinked cellulose particles were separated from the mother liquor using a glass filter, then neutralized with 1% by weight hydrochloric acid, and washed with a large excess of water. The obtained crosslinked cellulose particles had an average particle diameter of 80 μm and an exclusion limit molecular weight of 410 with polyethylene glycol.

Example 3 200 g of non-crosslinked cellulose particles having an exclusion limit molecular weight of 8200 obtained in step (2) of Example 1 were heated at 20°C for 1
After swelling in a 0% by weight aqueous sodium hydroxide solution, it was separated from the mother liquor using a glass filter, washed with water, and then replaced with methanol, then with a dimethyl sulfoxide solution, and filtered under suction. These dimethyl sulfoxide-containing non-crosslinked cellulose particles contain 5 dimethyl sulfoxide.
It contained 0 wt%.

200 g of the dimethyl sulfoxide-containing non-crosslinked cellulose particles (cellulose content: 100 g), 200 g of dimethyl sulfoxide, and 105 g of epichlorohydrin.
Pour g into a 1 liter flask and add 76 g of caustic soda while stirring.
280 g of an aqueous solution of caustic soda dissolved therein was added little by little. Addition of the caustic soda aqueous solution was carried out over 1 hour while adjusting the liquid temperature to 20°C. Then, the liquid temperature was increased to 50℃ for 1 hour.
After that, the crosslinking reaction was carried out at 50° C. for 3 hours.

After neutralization, the crosslinked cellulose particles produced are
Washed with water. The obtained crosslinked cellulose particles have an average particle size of 3
The exclusion limit molecular weight with polyethylene glycol was 2,000 at 2 μm.

Comparative Example 1 In Example 1, the non-crosslinked cellulose particles having an exclusion limit molecular weight of 8,200 were swollen in a 10% by weight aqueous sodium hydroxide solution at 20° C., and then filtered with suction through a glass filter.

Next, the swollen cellulose particles (100 g of cellulose component), 300 g of dimethyl sulfoxide, and 105 g of shrimp chlorohydrin were placed in a 1 liter flask and stirred, and the liquid temperature was raised to 50°C in 1 hour and then adjusted to 50°C. The crosslinking was completed. The crosslinked cellulose particles obtained by washing with water in the same manner as in Example 1 had an exclusion limit molecular weight of 9,000 with polyethylene glycol, which was larger than the exclusion limit molecular weight of non-crosslinked cellulose with an exclusion limit of 8,200.

Comparative Example 2 When the non-crosslinked cellulose particles of Example 1 with an exclusion limit molecular weight of 8,200 were subjected to the same crosslinking treatment as in Example 2 without swelling with a caustic soda aqueous solution, the exclusion limit molecular weight was 5.
It was 00.

[0066] The particles had a theoretical plate number of 600 plates/30 cm in ethylene glycol.

Although the exclusion limit molecular weight decreased as described above, a decrease in the number of theoretical plates was observed, and it was recognized that the crosslinking reaction was in a non-uniform state.

[0068]

Effects of the Invention: It was thought that it was difficult to reduce the size of the cellulose network through cross-linking reactions in the conventional cellulose fine particles, but after being swollen in the medium of the basic compound of the present invention, Only by carrying out a crosslinking reaction in an organic solvent did it become possible to produce cellulose particles with a small exclusion limit molecular weight. In addition, the method of the present invention has been able to sharpen the width of the separated peak when performing chromatographic separation by swelling in a medium containing a basic compound before the crosslinking reaction. .

Claims (1)

[Claims] Claim 1: (1) (a) consists essentially of a type II cellulose crystalline phase and a cellulose amorphous phase, (b) consists essentially of spherical or oblong spheroidal particles with an average particle diameter of 500 μm or less, and (c) preparing minute non-crosslinked cellulose particles whose exclusion limit molecular weight by polyethylene glycol is in the range of about 1,000 to about 10,000; (2) adding the minute non-crosslinked cellulose particles to a basic compound in a water-containing medium; (3) the swollen particles are separated from the water-containing medium, and (4) the separated particles are subjected to a crosslinking reaction in the presence of a basic compound in a hydrophilic aprotic organic solvent. and (5) the generated fine crosslinked cellulose particles are separated from the mother liquor and washed with water until the exclusion limit molecular weight is approximately 3.
A method for producing micro crosslinked cellulose particles having a small exclusion limit molecular weight, the method comprising producing micro crosslinked cellulose particles having a molecular weight of ,000 or less.