JPH01130726A - Gelatinous substance - Google Patents

Abstract

PURPOSE:To maintain durability of the title substance and to increase adsorbability of phsiologically active substance, etc., by prepg. gelatinous substance with cationized hydroxyalkylcellulose such as cross-linked glycidyltrimethylammonium chloride. CONSTITUTION:One or more kinds of cationizing agent such as glycidyltrimethylammonium chloride, dimethyldiallylammonium chloride is reacted with hydroxyalkylcellulose to obtain the cationized hydroxyalkylcellulose. Then, the cationized hydroxyalkylcellulose is reacted with a cross-linking agent to produce cross-linked cationized hydroxyalkylcelluose. The cross-linking agent above-mentioned is epichlorohydrin, 1,3-dichloro-2-propanol, 1,3-dibromo-2propanol, etc. The obtd. cross-linked cationized hydroxyalkylcellulose is a water-soluble gelatinous substance.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] This invention relates to a cationic and gel-like substance. In detail, nucleic acid separation agent, noquilogen separation agent, carrier used for immobilization of physiologically active substances, carrier used for immobilization of bacterial cells, biocatalyst, mutagenic substance removal agent, heavy metal removal agent, soil improvement agent 1,・Relates to cationic, gel-like substances used in a wide range of applications, including as base agents and water-absorbing resins.

[Conventional technology]

BACKGROUND ART Conventionally, a method using gel beads has been known as a method for efficiently adsorbing substances that are difficult to separate dissolved (or dispersed) in water. (For example, JP-A No. 61-34463) Gels that are widely used as stable aqueous gels are made by adding water-soluble polyvalent metal salts such as iron, calcium, and aluminum to an aqueous solution of water-soluble polysaccharides such as sodium carboxymethylcellulose and sodium alginate. However, these gels did not have sufficient durability in the form of gel beads. Japanese Patent Publication No. 61-259750
disclosed a method for making this gel into a hard gel.

Is this method cal? This is a method of obtaining a very hard and durable gel by immersing a homogeneous hydrous gel of oxymethylcellulose (CMC) in a concentrated polyvalent metal salt aqueous solution for an appropriate period of time. It was something.

However, when the gel-like substance produced in JP-A No. 61-259750 is used for adsorption of physiologically active substances in water, the performance for separating the physiologically active substances was not sufficient.

[Problem that the invention seeks to solve]

The present invention has been made in view of the above circumstances, and during use, while maintaining the improved durability of the gel,
The purpose of the present invention is to provide a gel-like substance with improved performance in adsorbing and separating physiologically active substances.

[Means for solving problems]

That is, the present invention solves the above problems by providing a gel-like substance obtained by reacting cationized hydroxyalkylcellulose with a crosslinking agent.

The cationized hydroxyalkyl cellulose used in the present invention is obtained by the reaction of a cationizing agent and hydroxyalkyl cellulose.

The cationizing agent used in the present invention is one that imparts cationic properties to hydroxyalkylcellulose by reacting with a base having active hydrogen, such as a water group in hydroxyalkylcellulose, such as acetic acid, glycidyltrimethylammonium chloride, glycidyltrimethylammonium chloride,
Examples include glycidyltrialkylammonium halides such as glycidyltriethylammonium chloride and glycidyltrimethylammonium bromide, dimethylnoallylammonium chloride, methylacryloyloxyethylenetrimethylammonium chloride, and 3-chloro-2-hydroxypropyltrimethylammonium chloride. Among these, preferred cationizing agents are glycidyltrimethylammonium chloride,
3-chloro-2-hydroxypropylammonium chlorideteary, the most preferred cationizing agent is 3-chloro-
2-hydroxypropylammonium chloride.

Conventionally used gel-like substances based on sodium carboxymethylcellulose or sodium alginate did not show any improvement in the sorption of organic substances dissolved (or dispersed) in water, but in the present invention, gel By introducing cationic groups using the above-mentioned cationizing agent into a polymeric substance, the ability to adsorb and separate organic substances such as physiologically active substances or inorganic substances such as metal ions is improved. When the preferred cationizing agents mentioned above are used, a gel with good separation performance can be obtained when the nitrogen content of the cationized hydroxyalkyl cellulose is 0.5 to 3.0%, but when other cationizing agents are used, In this case, it is difficult to increase the nitrogen content, making it difficult to obtain a gel-like substance with good separation performance.

The amount of the cationizing agent used is such that the nitrogen content in the reaction product between the cationizing agent and the hydroxyalkylcellulose is 0.
It is preferable to control the amount within the range of 5 to 3.0% by weight. For example, if the nitrogen content in the reaction product is within the above range, it is effective as a nucleic acid isolating agent in cell extracts. If the nitrogen content in the reaction product is less than 0.5% by weight, it is not preferable because nucleic acid separation will not be carried out efficiently.

The type of cationizing agent and the range of nitrogen content described above do not limit the present invention.

The hydroxyalkyl cellulose used in the present invention is a polymer compound represented by the following general formula.

In the formula, R1+ R2t R3 are the same or different groups, and represent hydrogen or an oxyalkylene group represented by the general formula +cnH2n-o+rrl, n is 2 or more, m is the degree of substitution, and X is a positive number.

The weight average molecule i of hydroxyalkylcellulose is 50
,000 to 2,000,000, and a practical gel material can be obtained within this range. Examples of the hydroxyalkylcellulose used in the present invention include tehahydroxyethylcellulose and hydroxyglobilcellulose.

The number of moles of ethylene oxide or glopyrene oxide added to these derivatives is usually 1.5 to 3, but as the number of moles added increases, the hygroscopicity increases, which is unfavorable for handling. 2. ．． 5 is desirable.

The method for producing cationized hydroxyalkylcellulose used in the present invention is not particularly limited, and can be produced by any known method.

For example, the method disclosed in JP-A-56-62801 is a method for producing cationic cellulose ether by reacting cellulose ethyl with glycidyl trialkylammonium halide in a mixed solvent consisting of water and a soluble organic solvent. This is a method for producing cationic cellulose ether, which is characterized in that barium hydroxide is used alone or in combination with other basic compounds as a catalyst.

The method disclosed in Japanese Patent Publication No. 59-42681 involves reacting a cellulose (D m ethylene conductor) and a propylene oxide derivative of cellulose with a glycidyl trialkylammonium salt in a mixed solvent consisting of water and an inert organic solvent. , Before the reaction, the cellulose derivative is added in advance to 1 unit of anhydrous glycose of the cellulose derivative in O, OS ~
This is a method for producing a cation-modified cellulose derivative, which is characterized in that it is treated with an alkaline substance in an amount of 0.3 times the mole.

The crosslinking agent used in the present invention is a substance that binds the molecules of hydroxyalkyl cellulose, which is a linear polymer, to each other with chemical bonds to form a polymer compound with a three-dimensional network structure, such as epichlorohydrin, 1,3-dichloro- 2-propanol, 1, 3-dibromo-2-propanol, 1,
A wide range of crosslinking agents may be mentioned, such as 4-bis-(2,3 epoxypropoxy)-butane. Among these crosslinking agents, 1,3-dichloro-2-prono, nor,
, 3-reso-0-mo-2-f lobanol is preferred, and when this is used, the crosslinking reaction proceeds easily under an alkali catalyst, and a water-soluble gel-like substance can be obtained. The amount of crosslinking agent used is preferably 0.3% by weight or more based on the cationized hydroxyalkyl cellulose.

If the amount of crosslinking agent used is less than 0.3 weight, soluble cationized hydroxyalkylcellulose will be included, making it unsuitable for use as a gel material.

Specifically, a method for producing a gel-like substance by reacting a cationized hydroxyalkylcellulose with a crosslinking agent is as follows. Using commercially available hydroxyalkylcellulose, a cationization reaction and a crosslinking reaction under an alkali catalyst can be carried out in any order or simultaneously. After the production of the hydroxyalkylcellulose, the hydroxyalkylcellulose is isolated, or the hydroxyalkylcellulose is subsequently subjected to a cationization reaction and a crosslinking reaction in any order or simultaneously under an alkali catalyst without isolation. , a crosslinked cationized hydroxyalkyl cellulose is produced.

The cross-linked cationized hydroxyalkyl cellulose P-s gel material produced by the above method is insoluble or swollen in water, and is different from water-soluble cationized hydroxyalkyl cellulose.

In the present invention, what is referred to as a gel-like substance refers to a substance in a solidified state in which a polymeric solute loses its independent mobility and aggregates into a three-dimensional structure by reacting with a crosslinking agent. A jelly-like substance in which a gel solidifies while containing a dispersion medium, a core gel-like substance in which a gel separates from a dispersion medium and solidifies, and a state in which these jelly-like or core gel-like substances and sol-like substances coexist. Contains substances such as

The gel-like substance of the present invention can be used in the form of an amorphous solid, for example, as a cold storage material, in the form of a sheet, as a bag material, or in the form of gel-like beads, as a packing material for r-chromatography. It can be applied to a wide range of applications such as

None of the preferred ranges described above limit the scope of claim 1.

〔Effect of the invention〕

The gel-like substance of the present invention is a nucleic acid separating agent, a gyronoene separating agent, a carrier used for immobilizing physiologically active substances, a carrier used for immobilizing bacterial cells, a biocatalyst, a mutagenic substance removing agent, and a heavy metal removing agent. It can be applied to a wide range of applications including soil conditioners, bag agents, and water-absorbing resins. For example, with the recent development of biotechnology, techniques are being developed to extract and utilize useful proteins from extracts and disrupted solutions, but during separation and purification, it is necessary to remove coexisting nucleic acids. . Conventionally, the nucleic acid removal agents used for this purpose are water-soluble! Rotamine sulfate and chitosan are known. These methods remove nucleic acids by coagulating and precipitating the nucleic acids, but they have the disadvantage that the nucleic acid removing agent remains in the solution. However, if the crosslinked cationized hydroxyalkylcellulose gel of the present invention is used for this purpose, effective nucleic acid removal can be performed without any residual removal agent remaining in the solution.

(Example 1) 2000 parts of t@rt-butanol, 220 parts of water, and 60 parts of sodium hydroxide were put into a flask equipped with a stirrer, a condenser, and a secondary funnel, and after dissolving the sodium hydroxide, 170 parts of powdered cellulose of about 1,500 ml was added and stirred for 120 minutes to perform alkali treatment.

Add 150 parts of ethylene oxide to the obtained slurry,
The reaction was carried out at 65°C for 100 minutes and then at 65°C for 100 minutes to synthesize hydroxyethyl cellulose. The reaction mixture was heated for 50'
Cool and add 400 parts of a 60% aqueous solution of 3-/Roro-2-hydroxyglopyltrimethylammonium chloride and 5 parts of 1,3-cyclo-2-noropanol to C.
The reaction was carried out at 0°C for 240 minutes to carry out cationization and crosslinking reaction of hydroxyethylcellulose. After the reaction was completed, excess sodium hydroxide was neutralized with acetic acid, and then the reaction mixture was distributed from door to door. The filtered mass was washed with water and then dried at 60° C. to obtain about 330 parts of crosslinked cationized hydroxyethyl cellulose. The resulting crosslinked cationized hydroxyethylcellulose has a nitrogen content of 22% and a weight of 4.5% of its own weight.
Absorbed 1 times more water.

In order to evaluate the function of cross-linked cationized hydroxyethylcellulose as a separation agent, a nucleic acid removal test was conducted as shown below. Cross-linked cationized hydroxyethyl cellulose 0.1 g, Shusei's thymus nucleic acid 1r
n9 was dissolved in 10 ml of 0.15 M NaCt solution and stirred for 10 minutes. Next, the crosslinked gel was centrifuged, and the supernatant was collected. As a result of measuring the amount of nucleic acids in this supernatant, it was confirmed that 98 nucleic acids were removed from the solution.

Further, no cross-linked cationization or residual droxyethyl cellulose was observed in this supernatant.

Example 2 220 parts of inzolopanol and 53 parts of an aqueous sodium hydroxide solution of Section 6.8 were placed in a flask equipped with a stirrer, a condenser, and a dropping funnel, and after stirring at room temperature for 10 minutes, hydroxyethyl cellulose (Daicel Chemical Industries, Ltd.) was added.
fisP600) and 60 parts at 20°C.
The alkali treatment was performed by stirring for a minute. Thereafter, 23 parts of a 60% aqueous solution of 3-chloro-2-hydroxypropyltrimethylammonium chloride containing 1% of 1,3-fuchloro-2-f-lonognol was added to this solution, and the temperature was raised to 50°C. , and stirred at this temperature for 3 hours. Next, 8 parts of a 10% aqueous hydrochloric acid solution was added to neutralize the slurry, and the slurry was then filtered. After washing the filtered mass with water, it was dried at 60°C.
A cross-linked cationized hydroxyethyl cellulose was obtained. The resulting crosslinked cationized hydroxyethyl cellulose had a nitrogen content of 1.7% and absorbed 5.6 times its own weight of water.

When this cross-linked cationized hydroxyethylcellulose was tested for nucleic acid removal in the same manner as in Example 1, it was found that 9
6% of the nucleic acid was removed, and no crosslinked cationized hydroxyethylcellulose remained in the solution.

Claims (6)

[Claims] (1) Gel-like substance made of cross-linked cationized hydroxyalkyl cellulose (2) Cationized hydroxyalkylcellulose is a cation selected from the group consisting of glycidyltrimethylammonium chloride, dimethyldiallylammonium chloride, methylacryloyloxyethylenetrimethylammonium chloride, glycidyltriethylammonium chloride, and 3-chloro-2-hydroxypropyltrimethylammonium chloride. 2. The gel-like material according to claim 1, which is a cationized hydroxyalkyl cellulose obtained by reacting one or more kinds of oxidizing agents with hydroxyalkyl cellulose. (3) Crosslinking is epichlorohydrin, 1,3-dichloro-
2-propanol, 1,3-dibromo-2-propanol, 1,4-bis-(2,3,epoxypropoxy)-
The gel-like substance according to claim 1, characterized in that the gel material is produced using one or more crosslinking agents selected from the group consisting of butane. (4) The gel-like substance according to claim 1, wherein the gel-like substance has a property of absorbing water from 3 to 50 times its own weight. (5) The cationized hydroxyalkyl cellulose has a molecular weight of 50,000 to 2,000 and is represented by the following general formula.
000 hydroxyalkyl cellulose ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R_1, R_2, R_3 represent groups that are the same or different from each other, and are represented by hydrogen or the general formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ Represents an oxyalkylene group, n is 2 or more, m is 1 to
10, X represents a positive number. ), and a cationized hydroxyalkyl cellulose obtained by a reaction with a cationizing agent. (6) The gel-like substance according to claim 1, wherein the cationized hydroxyalkyl cellulose is cationized hydroxyethyl cellulose.