JPH01229002A - Minute crosslinked cellulose particle and production thereof - Google Patents

Abstract

PURPOSE:To obtain the subject particle stable to chemicals, having high compression resistance and suitable as a filler for liquid chromatigraphy for the separation of proteins, etc., by crosslinking fine particles of coagulated viscose containing cellulose xanthate and neutralizing the crosslinked product. CONSTITUTION:Fine particles of coagulated viscose containing 5-60wt.% (in terms of cellulose) of cellulose xanthate are subjected to crosslinking reaction, neutralized with an acid and, as necessary, subjected again to crosslinking reaction. The produced fine particles of crosslinked cellulose are separated from the mother liquor and, as necessary, subjected to desulfurization, washing with an acid, washing with water or methanol and heat-treatment to obtain the objective particles composed of type-II crystalline cellulose phase and amorphous cellulose phase, containing crosslinking bond between molecular chains of cellulose in the amorphous cellulose phase, having a crystallinity of 5-45% determined by X-ray diffraction, consisting of spherical or ellipsoidal particles having an average particle diameter of <=300mum and having a critical rejection molecular weight of 4,000-1,000,000.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention relates to micro crosslinked cellulose particles and a method for producing the same. More specifically, the present invention relates to crosslinked microcellulose particles that are substantially made of regenerated cellulose and have an exclusion limit molecular weight of more than 4,000 and less than 1 million in liquid chromatography, and a method for producing the same.

(Prior Art) Particles of cellulose or its various derivatives have recently come to be widely used in various fields as chromatography materials, polymer carriers, cosmetic additives, lubricants, and the like.

In particular, attempts have been made to produce spherical cellulose particles as gel filtration media for liquid chromatography. For example, Japanese Patent Application Publication No. 57-38801 and the corresponding European Patent Publication No. 47,064, and US Pat.
390,691 and 446,189,
A cellulose organic acid ester solution dissolved in a solvent mainly composed of chlorinated hydrocarbons is suspended in an aqueous medium to form droplets of the solution, and the chlorinated hydrocarbon solvent in the droplet is evaporated to form cellulose. forming organic acid ester spherical particles,
The method for producing porous spherical cellulose particles by subsequently saponifying the same is characterized in that an acid or alkali is added to and mixed with the cellulose organic acid ester solution before suspending it in an aqueous medium. A method for producing porous spherical cellulose particles is described. Examples of the same publication describe porous spherical cellulose particles having a particle size of 50 to 100 μm and an exclusion limit molecular weight of about 2,000. However, the product produced by this method has the disadvantage that the crystallinity of the gel is low, and when the particle size of the gel is small, the pressure resistance at high speed is poor.

In addition, Hondama et al., by partially crosslinking the porous cellulose gel, the hydrogen bonds are broken and the network structure inside the gel becomes larger, increasing the exclusion limit molecular weight.
It has been reported that as crosslinking progresses further, the network structure gradually becomes smaller and the exclusion limit molecular weight decreases (Yoshiaki Motodama, Kazuaki Matsumoto, and Tadashi Hirayama 1 Journal of the Chemical Society of Japan, 19
81.1883-1889).

For example, Table 9 of the same paper shows that as a porous cellulose gel with an exclusion limit molecular weight of 4.600 is crosslinked with epichlorohydrin, the exclusion limit molecular weight increases, and at a certain degree of crosslinking, it reaches a maximum value of 1.
It is described that the molecular weight is 1,000, and gradually decreases to 6,000 as crosslinking further progresses.

[Problems to be Solved by the Invention] The object of the present invention is to produce regenerated cellulose or crosslinked microcellulose particles whose crystal phase consists essentially of Type 1 cellulose and whose exclusion limit molecular weight with polyethylene glycol is greater than 4,000. It is about providing.

Another object of the present invention is to provide micro crosslinked cellulose particles that have an exclusion limit molecular weight greater than 4000 and are therefore used for separating and fractionating relatively high molecular weight polymers.

Still another object of the present invention is to provide a novel method for producing the micro crosslinked cellulose particles of the present invention as described above.

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

[Means and effects for solving the problems 1 According to the present invention, the above objects and advantages of the present invention are achieved by: (a) consisting essentially of a type II cellulose crystalline phase and a cellulose amorphous phase; In the amorphous phase, crosslinks exist between cellulose molecular chains, (c) the degree of crystallinity determined by X-ray diffraction is in the range of 5 to 45%, and (d) the particle size is spherical or spherical with an average particle size of 300 μm or less. This is accomplished by micro-crosslinked cellulose particles, characterized in that they consist essentially of prolate spheroidal particles, and (e) have an exclusion limit molecular weight greater than 4000 and less than 1 million.

According to the present invention, the micro cellulose particles of the present invention have: (1) cellulose xanthate of 5
Prepare coagulated viscose fine particles containing ~60% by weight, (2) Neutralize the coagulated viscose fine particles by subjecting them to a crosslinking reaction, or neutralize them with an acid and subjecting them to a crosslinking reaction, and then ( 3) (i) separating the generated crosslinked cellulose fine particles from the mother liquor; (u) subsequent to step (1), subjecting them to desulfurization, pickling, water washing, or methanol washing; or (ii) step (i) or step It can be produced by the method of (ii) followed by heat treatment.

The micro crosslinked cellulose particles of the present invention are as described above (a) to (e).
It is characterized by having the following requirements. Each of these requirements will be explained below.

The micro crosslinked cellulose particles of the present invention essentially consist of a type 1 cellulose crystalline phase and a cellulose amorphous phase. Therefore, cellulose microparticles made of natural cellulose, ie type I cellulose, are completely different from the microparticles of the present invention.

As is well known, ■type cellulose and ■type cellulose are
Distinguished by line diffraction. ■The X-ray diffraction diagram of type cellulose shows the diffraction angle (2θ) that clearly exists in type I cellulose.
There is virtually no 15° diffraction peak.

That is, it is characterized by the distinct presence of diffraction peaks around an X-ray diffraction angle (2θ) of 20° derived from the (l O1) plane and (OO2) plane of the ■-type cellulose.

Secondly, crosslinks exist between cellulose molecular chains in the cellulose amorphous phase.

Further, the crosslinking between cellulose molecules existing in the cellulose amorphous phase connects the hydroxyl groups of the cellulose molecules to each other via the crosslinking agent molecule.

For example, when epichlorohydrin is used as a crosslinking agent, the degree of crosslinking can be determined by the absorbance of an absorption peak attributed to the CH stretching vibration of alkylene in an infrared absorption spectrum by the KBr tablet method, and is 0.065.
It preferably has an absorbance of -0.200mg-'・cm-'' from 0.094 to 0.190ff1g-'・c
More preferably, it has an absorbance of m-2.

Moreover, thirdly, the micro crosslinked cellulose particles of the present invention have X
- It is characterized by the degree of crystallinity determined by linear diffraction method, 5-4
It has a crystallinity of 5%. The micro crosslinked cellulose particles of the present invention preferably have a content of 7 to 45%, more preferably 1
It has a crystallinity of 0-45%. The microcrosslinked cellulose of the present invention is not amorphous but crystalline as specified by the crystallinity.

Fourthly, the micro crosslinked cellulose particles of the present invention essentially consist of spherical or elongated spherical particles with an average particle size of 300 μm or less. The micro crosslinked cellulose particles of the present invention are composed of such micro particles. The micro crosslinked cellulose particles of the present invention preferably have an average particle size of 2 to 150 μm and are highly pressure resistant, and particles of 20 μm or less are particularly suitable for high performance liquid chromatography. Further, the micro crosslinked cellulose particles of the present invention are substantially composed of spherical or elongated spherical particles. In this specification, the term "prolate spherical shape" is a concept that includes particles whose projected view or plan view has a shape such as an ellipse, an elongated circle, a pinnacle shape, or an oval shape. The micro crosslinked cellulose particles of the present invention are spherical or elongated as described above,
Therefore, they are different from particles that are rounded or irregularly shaped.

Fifth, the micro crosslinked cellulose particles of the present invention have an exclusion limit molecular weight of polyethylene glycol greater than 4,000 and less than 1,000,000. The exclusion limit molecular weight can be determined by filling a column with cellulose particles swollen with water and then using standard polyethylene glycol of known molecular weight.

In order to separate high-molecular compounds such as proteins according to their molecular weights, particles having an exclusion limit molecular weight larger than the molecular weight of the compound to be separated are required.

According to the present invention, the lower limit of exclusion limit molecular weight is 10.00.
It is possible to obtain microparticles with a molecular weight of 0 or an even larger value of 100,000. Therefore, it is possible to provide microparticles that are optimally designed depending on the molecular weight of the high molecular weight compound to be separated.

As physical property values characterizing the micro crosslinked cellulose particles of the present invention, the following may be further mentioned.

The cellulose constituting the micro crosslinked cellulose particles of the present invention is preferably one having a degree of polymerization generally in the range of 100 to 700. If the degree of polymerization is less than 100, the pressure resistance will decrease,
On the other hand, if it exceeds 700, the fine cellulose particles tend to deform, making it difficult to obtain uniform particles.

The micro crosslinked cellulose particles of the present invention have a fractionation index defined by the following formula: It is preferable that (F) is at least 0.6.In order to efficiently separate high molecular compounds such as proteins depending on their molecular weight, it is preferable that the fractionation index is as large as possible. More preferably, it is at least 1.0, and according to the present invention, an even more preferable fractionation index of 1.5 or more can be obtained.

Furthermore, the microcrosslinked cellulose particles of the present invention preferably have a fractionation index of at most 3.0, more preferably at most 2.0.

Further, it is preferable that the micro cellulose particles of the present invention have a wet pressure resistance of at least 5 kg/C♂ when packed in a column. In order to carry out the separation and fractionation of proteins and the like in a large amount and in a short time on an industrial scale, a material having a high pressure resistance when wet is suitable for use in the evening. More preferably,
At least 1 OkFi/clIi! According to the present invention, it is more preferable that the wet pressure resistance is 40 kg.
/cJ or more, or 80kg/c♂ or more can be produced. When packed in the same column, the smaller the particle size of the cellulose particles, the higher the column pressure will be. Since the cellulose fine particles of the present invention with a particle size of 10 μm can withstand a column pressure of 80 kg, there is a great advantage that particles with various particle sizes can be selected depending on the desired separation accuracy and throughput.

The method for producing micro crosslinked cellulose particles of the present invention will be explained below. According to the method of the present invention, as described above, the first
Coagulated viscose fine particles containing 5 to 60% by weight of cellulose xanthate in terms of cellulose are prepared in the step 2, and after subjecting the coagulated viscose fine particles to a crosslinking reaction in the second step, they are neutralized with an acid or After neutralization with water, a crosslinking reaction is carried out, and in a third step, (i) the generated crosslinked cellulose fine particles are separated from the mother liquor, or (ii) following step (i), desulfurization, pickling, water washing, or methanol or (iii) step (1) or step (u).
) followed by heat treatment.

The coagulated viscose fine particles used in the first step first include (A) an alkaline polymer aqueous solution of cellulose xanthate and a first water-soluble polymer compound other than the alkaline polymer compound; mixing an aqueous polymer solution and a second water-soluble anionic polymer compound to produce a fine particle dispersion of the aqueous alkaline polymer solution; It can be produced by coagulating the cellulose xanthate in the dispersion into fine particles containing the first water-soluble polymer compound by mixing the tate with a coagulant.

Further, the coagulated viscose fine particles used in the first step of the present invention are obtained by: (A) preparing an alkaline polymer aqueous solution of cellulose xanthate and the other first water-soluble polymer compound; and (B) preparing the above-mentioned Alkaline polymer aqueous solution and number average molecule f
il, 500 or more water-soluble polyethylene glycol or polyethylene glycol derivatives and heated at 55°C.
A fine particle dispersion of the aqueous alkaline polymer solution is produced at the above temperature, and (C) the dispersion is further heated to a temperature equal to or higher than the temperature at which the dispersion is produced, or the dispersion is heated to a temperature equal to or higher than that of the dispersion. It can be produced by mixing the xanthate with a coagulating agent to coagulate the cellulose xanthate in the dispersion into fine particles containing the first water-soluble polymer compound.

As described above, the first method and the second method include the step (A) of preparing an alkaline polymer aqueous solution of cellulose xanthate and a first water-soluble polymer compound, and a fine particle dispersion of an alkaline polymer aqueous solution. The method consists of a step (B) of producing cellulose and a step (C) of producing cellulose-containing microparticles, which are basically the same steps.

The first method and the second method are different in that the second polymer compound used in the above step (B) is anionic in the first method, but nonionic in the second method. do. First, a first method for producing coagulated viscose fine particles used in the present invention will be described below.

According to the first method, as described above, an aqueous alkaline polymer solution of cellulose xanthate and a first water-soluble polymer compound other than cellulose xanthate is prepared in step A, and fine particles of the aqueous alkaline polymer solution are dispersed in step B. A liquid is generated, and in step C, fine particles containing the first water-soluble polymer compound are generated. Step A of preparing an alkaline polymer aqueous solution of cellulose xanthate and a first water-soluble polymer compound other than cellulose xanthate is to simultaneously dissolve cellulose xanthate and a first water-soluble polymer compound other than cellulose xanthate in water or an alkaline aqueous solution. Alternatively, cellulose xanthate is first dissolved in water or an alkaline aqueous solution, and the first water-soluble polymer compound is dissolved in the obtained viscose, or the first water-soluble polymer compound is dissolved in water or an alkali aqueous solution. This can be carried out by dissolving cellulose xanthate in an aqueous solution and then dissolving the cellulose xanthate in the solution.

The above-mentioned dissolution can be carried out, for example, by mixing using a kneader or a high-viscosity stirring blade.

Cellulose xanthate may be obtained as an intermediate in the rayon manufacturing process or cellophane manufacturing process, and for example, cellulose concentration is 33% by weight and alkali concentration is 16% by weight.
And cellulose xanthate with a monovalent value of about 40 is suitable.

As the first water-soluble polymer compound, for example, a nonionic or anionic polymer compound is preferably used. Examples of the nonionic first water-soluble polymer compound include polyethylene glycol, polyethylene glycol derivatives, and polyvinylpyrrolidone. These polymer compounds have, for example, a number average molecular weight of 400 or more, and preferably have a number average molecular weight of 600 to 400,000.

As a polyethylene glycol derivative, for example, only the hydroxyl group at one end of polyethylene glycol has 1-1 carbon atoms.
8 alkyl group, a phenyl group substituted with an alkyl group having 1 to 18 carbon atoms, or a water-soluble compound blocked with an acyl group having 2 to 18 carbon atoms or an A-B-A' type block copolymer (A, (A' being the same or different and representing a polyethylene oxide block, and B representing a polypropylene oxide block) are preferably used. More specifically,
For example, polyethylene glycol monomethyl ether, polyethylene glycol monolauryl ether, polyethylene glycol monocetyl ethyl; polyethylene glycol monomethyl phenyl polyethylene glycol monononylphenyl ether, polyethylene glycol monoacetate, polyethylene glycol monolaurate; and polyoxyethylene propylene Coupolyoxypropylene block-polyoxyethylene block, etc. can be mentioned.

The anionic first water-soluble polymer compound preferably has, for example, a sulfonic acid group, a phosphonic acid group, or a carboxylic acid group as an anionic group. These anionic groups may be in the form of free acids or salts.

The first water-soluble polymer compound having a sulfonic acid group as an anionic group has a sulfonic acid group such as vinyl sulfonic acid, styrene sulfonic acid, methylstyrene sulfonic acid,
It can be derived from monomers such as allylsulfonic acid, methallylsulfonic acid, acrylamide metalpropanesulfonic acid or salts thereof.

Similarly, n first phosphones nM are used as anionic groups.
The water-soluble polymer compound can be derived from monomers such as styrenephosphonic acid, vinylphosphonic acid, or salts thereof.

Also, water-soluble polymer compounds having carboxylic acid groups as anionic groups could be derived from monomers such as acrylic acid, methacrylic acid, styrene carboxylic acid, maleic acid, itamonic acid, or salts thereof.

For example, the first water-soluble polymer compound having a carboxylic acid group can be prepared by polymerizing sodium acrylate alone or by mixing it with other copolymerizable monomers such as methyl acrylate according to a method known per se. It is supplied as a homopolymer or copolymer containing polymerized units of sodium acrylate. Furthermore, for example, a water-soluble polymer compound having a sulfonic acid group can be produced by sulfonating a styrene homopolymer.

The same applies to the case where the sulfonic acid group is derived from a monomer other than styrene sulfonic acid, and the case where the sulfonic acid group and the carboxylic acid group are respectively derived from the above monomers.

The first water-soluble anionic polymer compound preferably contains at least 20 mol % of polymerized units of the above-mentioned monomers having anionic groups. Preferred polymeric compounds include copolymers and homopolymers.

The water-soluble anionic polymer compound preferably has a number average molecular weight of at least 5,000, more preferably 10,000 to 3,000,000.

The water-soluble first anionic polymer compound used in step A is not limited to the vinyl type polymers mentioned above,
Other examples include carboxymethyl cellulose, sulfoethyl cellulose, and salts thereof such as Na salts.

According to the first method, as described above, first, in step A, an alkaline polymer aqueous solution is prepared. The aqueous polymer solution preferably has a cellulose concentration derived from cellulose xanthate of 3 to 15% by weight, more preferably 5 to 12% by weight.
The alkaline concentration is preferably adjusted to 2 to 1.
It is adjusted to 5% by weight, more preferably 5 to 10% by weight. Further, the amount of the first water-soluble polymer compound is preferably adjusted to 0.03 to 5 parts by weight per 1 part by weight of cellulose.

According to the first method, the alkaline polymer aqueous solution prepared and prepared in step A is then mixed with a second water-soluble anionic polymer compound in step B.

For mixing, any means capable of producing a fine particle dispersion of an aqueous alkaline polymer solution can be used. For example, mechanical stirring using stirring blades, baffles, etc., ultrasonic stirring, or mixing using a static mixer can be carried out alone or in combination.

The second water-soluble anionic polymer compound is preferably used as an aqueous solution, more preferably as an aqueous solution in which the second polymer compound has a concentration of 0.5 to 25% by weight, particularly preferably 2 to 22% by weight. , used. The aqueous solution preferably has a viscosity of 3 centipoise to 50,000 centipoise, particularly 5 centipoise to 30,000 centipoise at 20°C.

The alkaline polymer aqueous solution and the second water-soluble anionic polymer compound are 0.3 to 100 parts by weight of the second polymer compound per 1 part by weight of cellulose in the alkaline polymer aqueous solution, more preferably L to 45 parts by weight, particularly preferably 4 to 20 parts by weight, are used and mixed. The mixing is advantageously carried out at a temperature lower than the boiling point of carbon disulfide contained in the aqueous alkaline polymer solution, more preferably in the range of 0 to 40°C.

According to the research of the present inventor, when an acid-decomposable inorganic salt such as calcium carbonate is present as a dispersing agent in the alkaline polymer aqueous solution in Step A, for example, in an amount of 0:5 to 5% by weight, It has become clear that the morphology of the fine particles in the fine particle dispersion produced in the second step is maintained stably and well.

Examples of the second water-soluble anionic polymer compound include the same compounds as the above-mentioned examples of the anionic first water-soluble polymer compound.

The second water-soluble anionic polymer compound may be the same as or different from the first water-soluble polymer compound.

According to the present method for producing coagulated fine particles, the fine particle dispersion of the aqueous alkaline polymer solution produced in step B is then coagulated in step C.

The coagulation reaction described above is desirably carried out while adding a mixing operation to the produced dispersion.

Solidification by heating can be advantageously carried out at a temperature higher than the boiling point of carbon disulfide contained in the alkaline polymer aqueous solution, for example, at a temperature of 50° to 90°C. In the case of coagulation using a coagulant, there is no need to raise the temperature to this level, and the temperature is usually 0 to 40°C.
The coagulation can be carried out at a temperature of . As the coagulant, for example, lower aliphatic alcohols, alkali metal or alkaline earth metal salts of inorganic acids, and combinations thereof with the third water-soluble polymer compound are preferably used. The lower aliphatic alcohol may be linear or branched, and examples thereof include aliphatic alcohols having 1 to 4 carbon atoms such as methanol, ethanol, 1so-propanol, n-propanol, and n-butanol. Preferably used. Examples of alkali metal salts of inorganic acids include Na2Cl, Na
, SO, and salts such as K, SO4 are preferable, and alkaline earth metal salts include, for example, MgSO,
Mg salts such as, Ca salts such as CaCl are preferred.

As the third water-soluble polymer compound, for example, nonionic and anionic polymer compounds are preferably used. It is particularly desirable to use the same third water-soluble polymer compound as the second anionic polymer compound used in step B.

Examples of the third water-soluble polymer compound will be understood from the above-mentioned examples of the first water-soluble polymer compound.

The coagulant as described above is used in a proportion of, for example, about 20 to 300% by weight based on the cellulose in hiscose.

Next, a second method for producing coagulated viscose fine particles used in the present invention will be explained.

According to the second method, as described above, an alkaline aqueous polymer solution of cellulose xanthate and a first water-soluble polymer compound other than cellulose xanthate is prepared in step A, and fine particles of the alkaline aqueous polymer solution are prepared in step B. A dispersion liquid is produced, and in step C, fine particles containing cellulose are produced. In this respect, it is basically the same as the first manufacturing method described above, as described above. Step A of preparing an alkaline polymer aqueous solution of cellulose xanthate and a first water-soluble polymer compound other than cellulose xanthate is carried out in the same manner as the method described in the description of the first manufacturing method above. For example, the xanthate and other first water-soluble polymer compounds used are the same as those described in the first production method.

Step B of producing a fine particle dispersion of an alkaline polymer aqueous solution includes an alkaline polymer aqueous solution and a number average molecular weight of 1500.
This is carried out by mixing the above water-soluble polyethylene glycol or polyethylene glycol derivative.

The high molecular weight polyethylene glycol or polyethylene glycol derivative used has a number average molecular weight of 1.500 or more, preferably 1.50.
It has a number average molecular weight of 0 to 400,000.

As a polyethylene glycol derivative, for example, only the hydroxyl group at one end of polyethylene glycol has 1-1 carbon atoms.
8 alkyl group, a phenyl group substituted with an alkyl group having 1 to 18 carbon atoms, or a water-soluble compound blocked with an alkyl group having 2 to 18 carbon atoms or an A-B-A' type block copolymer (A, (A' are the same or different and represent a polyethylene oxide block, and B represents a polypropylene oxide block) are preferably used. More specifically, for example, polyethylene glycol monomethyl ether, polyethylene glycol monolauryl ether, polyethylene glycol monocetyl ethyl; polyethylene glycol monomethyl phenyl ether, polyethylene glycol monononylphenyl ether: polyethylene glycol monoacetate, polyethylene glycol monolaurate; and polyoxy Examples include ethylene block-polyoxypropylene block and polyoxyethylene block.

Among polyethylene glycol and its derivatives, polyethylene glycol is more preferred, and has a number average molecular weight of 6,
A number average molecular weight of 8.000 to 200,000 is more preferred, a number average molecular weight of 8.000 to 100.000 is particularly preferred, and a number average molecular weight of 10.000 to 30.000 is especially preferred.

The polyethylene glycol derivative is preferably 1.500
It has a number average molecular weight of ~16,000.

According to the second method, in step B, an alkaline aqueous polymer solution and a water-soluble high molecular weight polyethylene glycol or a derivative thereof are first mixed. For mixing, any means capable of producing a fine particle dispersion of an alkaline aqueous polymer solution can be used. The specific means are as described in the description of the first manufacturing method above.

The water-soluble high molecular weight polyethylene glycol or its derivative is preferably used as an aqueous solution, more preferably the concentration of the polyethylene glycol or its derivative is from 0.5 to
60% by weight, particularly preferably 5-55% by weight, especially 10% by weight
It is used as a ~40% by weight aqueous solution.

The alkaline polymer aqueous solution and polyethylene glycol or polyethylene glycol derivative are 1 to 30 parts by weight, more preferably 2 to 28 parts by weight, particularly preferably 4 to 24 parts by weight, and particularly preferably 4 to 24 parts by weight of polyethylene glycol or polyethylene glycol derivative per 1 part by weight of cellulose. It is used in an amount of 8 to 16 parts by weight and mixed. Although there is no particular restriction on the temperature during mixing, it is desirable to carry out the mixing at a temperature lower than the temperature at which a fine particle dispersion of the aqueous alkaline polymer solution is produced. The fine particle dispersion of the aqueous alkaline polymer solution is produced at a temperature of 55°C or higher. At temperatures lower than 55° C., it is not possible to obtain a fine particle dispersion of the basic aqueous alkaline polymer solution capable of providing the desired fine cellulose particles.

According to the second method, the fine particle dispersion of the aqueous alkaline polymer solution produced in step B is then solidified in step C.

Further, the coagulation reaction is carried out at a temperature equal to or higher than the temperature at which the dispersion is produced.

Both coagulation by heating and coagulation using a coagulant are preferably 6
It is carried out at a temperature of 0°C to 90°C, but it can also be coagulated with a coagulant at a temperature below 60°C.

The coagulant and its usage ratio are the same as described in the description of the first manufacturing method above.

When a combination of polyethylene glycol or its derivatives is used as the coagulant, the addition of the coagulant can prevent the concentration of polyethylene glycol or its derivatives in the system from decreasing. It has the advantage that coagulation can be carried out stably.

The coagulated viscose fine particles crushed by the first method and the second method as described above consist essentially of spherical to long spherical particles with an average particle diameter of 400 μm, and have a cellulose component of 5
~60% by weight (in terms of cellulose). The cellulose component of the coagulated viscose fine particles referred to here is obtained by washing and replacing water and water-soluble polymer compounds attached to the surface of the fine particles with excess n-hexane, and drying at 50°C for 160 minutes to remove the attached n-hexane. After removal, the particles were heated at 105°
c. Dry for 3 hours to determine the cellulose component. In addition, if a water-soluble polymer compound is contained, the contained polymer compound is removed by washing with water in advance when determining the cellulose component. The polymer compound in the coagulated viscose fine particles was removed using 0.5 to 2% by weight of caustic soda at a temperature of 20%.
Performed at ~30°C.

According to the present invention, the coagulated viscose fine particles from which the polymer compound has been removed in the first step are subjected to a crosslinking reaction in the second step, and then neutralized with an acid to form viscose. It is converted into cellulose or neutralized with acid and then subjected to a crosslinking reaction. As the crosslinking agent, epichlorohydrin, dichlorohydrin, etc. are used.

The crosslinking reaction is carried out using coagulated viscose fine particles or regenerated cellulose particles in a liquid medium containing alkali hydroxide. When the alkali hydroxide is caustic soda, it is carried out at a concentration of 1 to 25% by weight, preferably 5 to 15% by weight. The crosslinking agent is present in the liquid medium containing the alkali hydroxide.
The concentration is adjusted to % by weight. As the liquid medium, water or methanol which is compatible with water and is a good solvent for the crosslinking agent;
Ethanol or acetone etc. are used alone or in a mixture with water.

The liquid medium is used in an amount of 10 to 30 parts by weight per 1 part by weight of cellulose. It varies depending on the liquid medium, but usually 50~
The crosslinking reaction is carried out at a temperature of 80°C.

The higher the alkali hydroxide concentration and the higher the crosslinking agent concentration, the larger the pore volume inside the particles, and by appropriately selecting the crosslinking conditions, the pore diameter and pore amount inside the crosslinked cellulose particles subjected to heat treatment can be adjusted. Can be done.

The method of the present invention is characterized in that the degree of crystallinity hardly changes before and after the crosslinking reaction and heat treatment.

It is presumed that crosslinks between cellulose molecular chains exist partially as a grafting technique, in the form in which the hydroxyl groups of the cellulose molecules are substituted with hydroxyl groups, or in the form in which they are substituted with hydroxyl groups and interrupted by oxygen atoms.

As the acid used for converting into cellulose in the second step, strong inorganic acids such as sulfuric acid and hydrochloric acid are preferably used.

Next, in the third step, crosslinked cellulose fine particles are separated from the mother liquor. After separation, desulfurization, pickling, water washing, or methanol washing can be carried out if necessary, and heat treatment can also be carried out afterwards or after the above-mentioned separation.

Desulfurization can be carried out using an aqueous alkali solution such as caustic soda or sodium sulfide. If necessary, in order to remove residual alkali, it is then pickled with dilute hydrochloric acid or the like, and then washed with water or methanol. Heat treatment is 60-120
It is carried out at a temperature of °C, and the treatment is carried out under dry heat or moist heat conditions. The heat treatment machine may be a vacuum dryer, an autoclave, a commonly used hot air dryer, or an evaporator.

A heat treatment time of 20 minutes to 6 hours is usually sufficient.

The heat treatment characteristics vary depending on the crosslinking conditions of the crosslinked cellulose particles subjected to heat treatment, and the crosslinking agent concentration is 20 to 25% by weight.
and the alkali hydroxide concentration in the liquid medium is 8 to 1.
When the content is as high as 2% by weight, the exclusion limit molecular weight can be lowered while maintaining the above-mentioned F value high. By appropriately selecting crosslinking conditions and performing heat treatment, crosslinked cellulose particles having various F values and exclusion limit molecular weights can be obtained.

(Example) 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 first.

<Absorbance of OH stretching absorption band> Precisely weigh 1 to 3 mg of micro cellulose particles, and add approximately 200 mg of potassium bromide powder (abbreviated as KBr) for infrared absorption spectrum measurement.
Weigh precisely mg, and thoroughly knead and grind both in an agate mortar. Next, the cellulose particles and the cross-pulverized KBr powder are collected and used in a tablet molding machine to form a KBr tablet for infrared absorption spectrum measurement, and the transmittance infrared absorption spectrum is measured. 2800-30 in the obtained infrared spectrum
The absorbance of the OH stretching absorption band having a peak at 00 cm-' is determined and converted to the absorbance per 1 mg of cellulose. That is, W; micro cellulose particle collection amount (mg), M
; KBr powder collection amount (mg), m; KBr tablet weight (mg), A, absorbance of OH stretching absorption band, T(P); transmittance at peak top of OH stretching absorption band (%), T(b ); Baseline transmittance (%) at the peak wave number of the OH stretching absorption band. However, the baseline is 2000-4
In the range of 000 cm-', the peak base areas of both the OH stretching absorption band and the OH stretching absorption band are drawn so as to be tangential.

Ao is the absorbance of the CH stretching absorption band per 1 mg of micro cellulose particles, where A -log + o T (b) / T C
P) A (M+w) Ao=-m + W.

<Method for measuring crystallinity> Journal of the Japan Institute of Textile Science and Technology, Vol. 19, Nhe 2 (1963), pp. 113-
It is determined by the cellulose crystallinity measurement method using the X-ray diffraction method described on page 119. That is, an X-ray diffraction curve from 2θ or 5° to 45″ is taken and calculated using the following formula.

Crystallinity (%)-X I OO T' where, T'-((a+C)-b)xKK=0.896
(Incoherent scattering correction coefficient of cellulose) -c-a a: Diffraction curve of non-quality starch (2θ = 5 to 45°)
b: Area of air scattering curve (2θ = 5 to 45°), C: Area of sample diffraction curve (2θ-5 to 45°), Average degree of polymerization> Determined according to the method described in JIS L-1015 T-ko.

Average Particle Size Measurement Method Approximately 0.12 samples were taken, poured into 25 mQ of pure water, stirred and dispersed, and measured using a light transmission particle size distribution analyzer.

Molecular weight fractionation characteristics> Micro cellulose particles were each filled into a 9 mmu x 15 mm resin column using water as a filling liquid at a flow rate of 4.0 mQ/min for 60 minutes. Next, using each packed column as a separation column, plot the relationship between elution time and molecular weight using standard polyethylene glycol of known molecular weight under the analysis conditions below, and calculate the exclusion limit molecular weight as the molecular weight of polyethylene glycol at the bending point of the curve. demand.

Moreover, the fractionation index (F) is determined by the following formula.

D Where ■ Elution volume (mQ) of Niblue dextran (molecular weight 2 million) V8: Elution volume (mi2) of ethylene glycol Analysis conditions 1, Pump At-Co., Ltd. Peristal Pump 5J-12
11H type, 2. Eluent: pure water, 3° flow rate: 1, Q mQ/min.

4. Temperature: room temperature, 5. Detector: R1 detector, Example 1 Pulp 5002 made of coniferous wood at 20°C, 518% by weight
It was immersed in a 20Q caustic soda solution for 1 hour and squeezed 2.8 times. Milled for 1 hour while heating from 25°C to 50°C, aged, and then treated with 33fIi for cellulose.
% of carbon disulfide (1657) was added 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 6,200 centipoise.
child.

The above-prepared viscose 120.9 and an aqueous solution of sodium polyacrylate (polymer concentration 12% by weight, molecular weight 50,000) 4802 as an anionic polymer compound were placed in an IQ flask to make a total amount of 6002. At a liquid temperature of 30°C, use a laboratory stirrer (manufactured by Yamato Scientific Co., Ltd.: MODEL L).
R-51B.

After stirring at 600 rpm for 10 minutes to generate fine viscose particles, the liquid temperature was raised from 30°C to 70°C in 15 minutes with continued stirring, and at 70°C. This was maintained for 10 minutes to solidify the viscose microparticles. The coagulated viscose particles were separated from the mother liquor by a type IG4 glass filter. The obtained coagulated viscose particles had a particle size of 80 μm and a cellulose component of 45
% by weight (in terms of cellulose).

Next, the coagulated viscose particles were washed with a 0.5% by weight aqueous solution of caustic soda, and then washed with an IG4 type glass filter.
02 was filtered and mixed with stirring in an 8% by weight aqueous solution of caustic soda containing 20% by weight of epichlorohydrin.
C. for 3 hours.

Subsequently, the particles were separated from the mother liquor using a glass filter, and then neutralized with 5% by weight hydrochloric acid to form crosslinked cellulose fine particles, which were washed with a large excess of water. The properties of the obtained crosslinked microcellulose particles are shown in Table 1, Run No. 1.

Further, the molecular weight fractionation characteristics of Run No. 1 are shown in FIG.

Example 2 In Example 1, the epichlorohydrin concentration was changed to 5.
15. The characteristics of crosslinked microcellulose particles obtained by the same method except that the amount was changed to 25% by weight are shown in Table 1.
Shown in NQ, 2, Run No. 3, Run NQ, 4.

Example 3 The coagulated particles obtained in Example 1 were neutralized with 5% by weight hydrochloric acid, filtered through a glass filter, and mixed with stirring in a 12% by weight aqueous solution of caustic soda IQ containing 25% by weight of epichlorohydrin. Crosslinked at °C for 13 hours. After successively filtering with a glass filter and washing with water and methanol, heat treatment was performed for 10,500,015 hours. The properties of the obtained wood grain wet crosslinked microcellulose particles are shown in Table 1.
un NQ.

5, and the molecular weight fractionation characteristics are shown in FIG.

In addition, Run No. 6 shows the characteristics of crosslinked particles without heat treatment.

Example 4 After dissolving the xanthate obtained in Example 1 in a caustic soda aqueous solution, polyethylene glycol (molecular weight 6000)
500 & was added and dissolved to prepare an aqueous alkaline polymer solution of cellulose xanthate and polyethylene glycol. The alkaline polymer aqueous solution has a cellulose concentration of 9
．． 3% by weight, caustic soda concentration 6.1% by weight, polyethylene glycol 9.1% by weight, and viscosity 7400 centipoise. Alkaline polymer aqueous solution 602 prepared above
and an aqueous solution of sodium polyacrylate as an anionic polymer compound (polymer concentration 12% by weight, molecular weight 50,000) 2
40j? was placed in a 500-flask, making the total amount 3009. Viscose fine particles containing polyethylene glycol were coagulated in the same manner as in Example 1. The coagulated viscose particles were separated from the mother liquor by a lGd type glass filter. Then, the coagulated viscose particles were added to 0.5
The polyethylene glycol was washed away with a wt % aqueous solution of caustic soda. The resulting coagulated viscose particles had a particle size of 85μ.
m, and the cellulose component was 31% by weight. The obtained coagulated viscose particles 602 were cross-linked for 13 hours at 60°C while stirring in 500 d of a 5% by weight aqueous sodium hydroxide solution containing 25% by weight of epichlorohydrin. Subsequently, the same treatment as in Example 1 was carried out to obtain crosslinked microcellulose particles. Its properties are shown in Table 1, RunNa, 7.

Further, its molecular weight fractionation characteristics are shown in FIG.

Example 5 The xanthate obtained in Example 1 was dissolved in an aqueous solution of caustic soda to prepare viscose. The viscose has a cellulose concentration of 1000% by weight and a caustic soda concentration of 6.21% by weight.
Met.

3g, 16g and 30g of polyethylene glycol (molecular weight 4000) were added and mixed to 60g of the viscose prepared above to obtain an alkaline polymer aqueous solution.

Each of the alkaline polymer aqueous solutions and 240 g of an aqueous solution of sodium polyacrylate (polymer concentration 12% by weight, molecular weight 50,000) as an anionic polymer compound were placed in a 500 mQ flask, and polyethylene glycol was added in the same manner as in Example 4. The viscose fine particles containing the following were coagulated. Thereafter, the same operation as in Example 4 was performed to obtain crosslinked microcellulose particles.

Its characteristics are shown in Table 2 Run No. 8 to Run No. l
Shown in O. In addition, Run No. and Il show the characteristics when no polyethylene glycol was added. Figure 2 shows the molecular weight fractionation characteristics of Run No. 8, No. 1O1 No. 11(').

Table 2 Example 6 The coagulated viscose particles (80 μm) obtained in Example 1 were neutralized with 5% by weight hydrochloric acid to obtain regenerated cellulose particles. l
60 g (cellulose equivalent) was filtered through a GJ type glass filter, and poured into a 12% by weight aqueous solution of caustic soda IQ containing 20% by weight of epichlorohydrin at 50°C for 3 hours with stirring.
Time crosslinked. After subsequent separation from the mother liquor through a glass filter, the particles were neutralized with 5% by weight hydrochloric acid to form crosslinked cellulose particles, which were washed with a large excess of water. Furthermore, the crosslinked cellulose particles were washed with methanol and then heat-treated in a ventilation dryer at 105° C. for 5 hours. The properties of the crosslinked microcellulose particles rewetted with the obtained water are shown in Table 3 Run No. 12.
It was shown to. In addition, Run No. 13 showed the characteristics of crosslinked fine cellulose particles that were not heat-treated.

Example 7 500 g of viscose obtained in Example 1 and 270'i of an aqueous solution of sodium polyacrylate (polymer concentration 14% by weight, molecular weight 700,000) as an anionic polymer compound
11 Jl! The total amount was 3002. At a liquid temperature of 30°C, stirring was performed using a lab stirrer at 80 rpm for 10 minutes to generate fine viscose particles, and then the liquid temperature was increased from 30°C to 7°C while continuing to stir.
The temperature was raised to 0°C in 15 minutes and maintained at 70°C for 10 minutes to solidify the viscose fine particles. Separated from the mother liquor with a glass filter (lG4) and then 5% by weight
Regenerated cellulose fine particles were obtained by neutralizing with hydrochloric acid and washing with a large excess of water. 60 g of the cellulose fine particles (dry equivalent) were mixed with 1 containing 20% by weight of epichlorohydrin.
While stirring in a 2% by weight aqueous solution of caustic soda lQ,
Crosslinked for 0.3 hours. It was subsequently separated from the mother liquor through a glass filter, neutralized with 5% by weight hydrochloric acid and washed with a large excess of water. Further, the crosslinked cellulose fine particles were washed with methanol and then heat treated in a ventilation dryer at 105°C for 5 hours. The properties of the crosslinked microcellulose particles rewetted with water are shown in Table 4, Run No. 14.

As shown in FIG. 3, the crosslinked microcellulose particles obtained in this example are characterized by excellent pressure resistance.

Example 8 60 tons of viscose obtained in Example 1 and an aqueous solution of polyethylene glycol (polymer concentration 40% by weight, molecular weight 20,000) were placed in a 500 flask, and the total amount was 30
It was set as 02.

At a liquid temperature of 30°C, stir with a lab stirrer at 100°rpm for 10 minutes, raise the liquid temperature from 30°C to 70°C in 15 minutes, maintain it at 70°C for 30 minutes, and stir viscose. The fine particles were solidified. The obtained coagulated viscose particles had a particle size of 18 μm and a cellulose content of 48% by weight (in terms of cellulose).

The characteristics of the crosslinked microcellulose particles obtained in the same manner as in Example 1 are shown in Table 4, Run Ha, l 5.
I.

Table 4, Table 3, Claim 1, wherein the bridge between the cellulose molecular chains is an alkylene substituted with a hydroxyl group or an alkylene substituted with a hydroxyl group and interrupted by an oxygen atom, which connects the hydroxyl groups of the cellulose molecules. Microcrosslinked cellulose particles as described.

4. In the infrared absorption spectrum obtained by the KBr tablet method, the absorbance of the absorption peak attributed to CH stretching vibration is 0.0.
Micro crosslinked cellulose particles according to claim 1, in the range of 65 to 0.200 mg-', cm-''.

5. In the infrared absorption spectrum obtained by the KBr tablet method, the absorbance of the absorption peak attributed to CH stretching vibration is 0.0.
94 to 190 mg-', cm-'' micro crosslinked cellulose particles according to claim 1.

6. Micro crosslinked cellulose particles according to claim 1, having a crystallinity in the range of 7 to 45%.

7. Micro crosslinked cellulose particles according to claim 1, which essentially consist of spherical or prolong spherical particles having an average particle diameter of 2 to 150 μm.

8. The micro crosslinked cellulose particles according to claim 1q4, which essentially consist of spherical or oblong spherical particles having an average particle size of 20 μm or less.

9. The projection of a long spheroidal particle is an ellipse, an elongated circle,
The micro crosslinked cellulose particles according to claim 1, which are peanut-shaped or egg-shaped.

The micro crosslinked cellulose particles according to claim 1, which have a lO1 exclusion limit molecular weight of 6.000 or more.

11. The micro crosslinked cellulose particles according to claim 1, which have an exclusion limit molecular weight of 1,000 or more.

12. Micro crosslinked cellulose particles according to claim 1, wherein the degree of polymerization of cellulose is in the range of 100 to 700.

13. The following formula VD is the elution volume (IIlβ) of blue dextran (molecular weight 2 million), and ■ is the elution volume (12) of ethylene glycol. The fractionation index (F) defined by is at least 0. .6. The micro crosslinked cellulose particles according to claim 1, wherein

14. Micro crosslinked cellulose particles according to claim 1, which have a fractionation index (F) of at least 1.0.

15. The micro crosslinked cellulose particles according to claim 1, having a fractionation index (F) of at most 3.

16. The micro crosslinked cellulose particles according to claim 1, having a wet pressure resistance of at least 5 kg/c♂.

17. Pressure resistance when wet is at least l Okg/c++
The micro crosslinked cellulose particles according to claim 1, which are ``+''.

18. The method according to claim 17, wherein the coagulated viscose fine particles used in step (1) have an average particle size of 400 μm or less.

19. The method according to claim 17, wherein the crosslinking reaction in step (2) is carried out in a liquid medium containing 1 to 25% by weight of alkali hydroxide.

20. The method according to claim 19, wherein the alkali hydroxide is caustic soda or caustic potassium.

21. The method according to claim 19, wherein the liquid medium is an aqueous medium consisting of water and an organic solvent that is compatible with water and is a good solvent for the crosslinking agent.

22. The method of claim 19, wherein the liquid medium is water.

23. The method according to claim 17, wherein the heat treatment in step (3) is carried out at a temperature of 60 to 120°C.

(Effects of the Invention) As described above, the micro crosslinked cellulose particles of the present invention essentially consist of a type cellulose crystalline phase and a cellulose amorphous phase, in which crosslinks exist between cellulose molecular chains in the cellulose amorphous phase, and The crystallinity determined by the linear diffraction method is in the range of 5 to 45%, the average particle size is substantially spherical or long spherical particles of 300 μm or less, and the exclusion limit molecular weight by polyethylene glycol is greater than 4000. The value is less than 1 million yen, and it is relatively stable against chemicals.
Since it has good pressure resistance, it can be suitably used as a liquid chromatography packing material for separating high molecular compounds such as proteins.

[Brief explanation of the drawing]

Figure 1 shows the micro crosslinked cellulose particles of the present invention (Example 1).
:RunNa, l, Example 3: Run No, 5
, Run No. 7) is a diagram showing the relationship between the molecular weight and elution time of polyethylene glycol showing the separation performance as a packing material for liquid chromatography. Figure 2 shows the micro crosslinked cellulose particles of the present invention (Example 5).
: Run N (L8, Run Na, 10, R
It is a figure showing the separation performance of un No. 11) as a packing material for liquid chromatography. Figure 3 shows micro crosslinked cellulose particles of the present invention (Example 1:
It is a figure showing the relationship between column pressure and flow rate showing the pressure resistance performance of RunNa, 1, Example 7: RunNQ, 14) as a packing material for liquid chromatography. 1 other person

Claims (1)

[Claims] 1. (a) substantially consists of a type II cellulose crystalline phase and a cellulose amorphous phase, (b) crosslinks exist between cellulose molecular chains in the cellulose amorphous phase, (c) The degree of crystallinity determined by line diffraction is in the range of 5 to 45%, (d) the average particle size consists essentially of spherical or prolate particles with an average particle size of 300 μm or less, and (e) the particle size is larger than 4000 μm and 100 μm or less. Micro crosslinked cellulose particles having an exclusion limit molecular weight of less than 10,000. 2. (1) Cellulose xanthate is 5 in terms of cellulose.
Prepare coagulated viscose fine particles containing ~60% by weight, (2) Subject the coagulated viscose fine particles to a crosslinking reaction and then neutralize with an acid, or neutralize with an acid and then subject to a crosslinking reaction, and then ( 3) (i) Separating the produced crosslinked cellulose fine particles from the mother liquor, (ii) Subsequently to step (i), subjecting them to desulfurization, pickling, water washing, or methanol washing, or (iii) step (i) or step The method for producing micro crosslinked cellulose particles according to claim 1, characterized in that (ii) is followed by heat treatment.