JPH06192425A - Aminomethylated polysulfone and its production - Google Patents

Abstract

PURPOSE:To provide a new arom. polysulfone excellent in reaction characteristics and to provide a molding, etc., made therefrom. CONSTITUTION:An arom. polysulfone having side chains of the formula: R-NH-- CH2(wherein R is H, lower alkyl, or benzyl) attached to the backbone is provided together with a molding made of therefrom The polymer or the molding is produced by hydrolyzing an acylamidomethylated arom. polysulfone or its molding in the presence of an acid catalyst. The obtd. polymer is useful for treatments such as adsorption, separation, and immobilization of an ionic substance, a physiologically active substance, etc.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an aromatic polysulfone polymer having a specific aminomethyl group introduced as a side chain or a molded product thereof. More specifically, it relates to adsorption of ionic substances and physiologically active substances. The present invention relates to an aminomethylated polysulfone polymer that can be suitably used for separation, immobilization and the like or a molded product thereof, and a method for producing them.

[0002]

2. Description of the Related Art Conventionally, a substance in which a specific physiologically active substance is immobilized on an insoluble carrier has been used as an adsorbent for affinity chromatography, a blood treating agent for treatment, a cell culture device, an antibacterial material, and other analytical reagents. It is an important field for which widespread applications are expected in the future.

Further, polymers having reactive functional groups, especially primary and secondary amino groups, can be used for immobilization of physiologically active substances and the like, so that they are adsorbents for affinity chromatography and therapeutic blood. It is useful as a raw material for treating agents and antibacterial materials. Further, when the polymer is soluble, it is particularly useful because it can be molded into various shapes and used suitably. As a polymer having primary and secondary amino groups, a polystyrene derivative is well known, but it has a limitation in molding because it is a brittle polymer, and for example, it has a drawback that it cannot be molded into a hollow fiber or a catheter. is there.

Aromatic polysulfones are widely used as engineering plastics because of their good moldability, but they are also partially used in the form of hollow fibers for substance separation. By introducing a reactive functional group into the polysulfone, the polysulfone can be used for immobilization of a physiologically active substance, selective separation of the substance, and the like, and is expected to have a wider range of applications.

However, the reaction for introducing a reactive functional group into the polysulfone is not well known, and the sulfonation reaction [A. Noshay, L .; M. Robeso
n, Journal of Applied Poly
mer Science, 20, 1885 (197)
6)] and halomethylation reaction [A. Warshaws
y and others, Journal of Polymer S
science, Part A, Polymer Ch
Only a few examples are known, such as "emission", 28, 2885 (1990)].

Also in these cases, an amino group cannot be derived from the former, and an amino group can be theoretically derived from the latter, but a reagent having high carcinogenicity (alkylhalomethyl ether) must be used. There is a defect that the polymer does not exist or the soluble polymer gels. Further, considering the process of deriving an amino group from a halomethyl group, a method of once reacting with potassium phthalimide to form a phthalimide derivative and then hydrolyzing with hydrazine or caustic soda can be considered. The main chain is hydrolyzed by alkali, so it cannot be used in practice. Further, the method of directly acting ammonia on the halomethylated polysulfone is not preferable because a crosslinked polymer can be obtained.

[0007]

Therefore, in view of the problems of the prior art, the present inventors have made various studies as to whether polysulfone having an amino group introduced can be obtained by a simple method, and as a result, N-methylol has been obtained. After preparing a soluble haloacetamidomethylated polysulfone by an amide methylation reaction method using -α-chloroacetamide, it was further found that an aminomethylated polysulfone can be prepared by acid hydrolysis of the haloacetamidomethyl sulfone, and the present invention was reached. did.

That is, an object of the present invention is to provide a novel soluble aminomethylated aromatic polysulfone polymer useful as a treatment material for adsorption, separation, fixation and the like of ionic substances and physiologically active substances. Is.

Further, the present invention provides a molded article of a specific form, which is composed of the aminomethylated aromatic polysulfone polymer, which can be suitably used for adsorption, separation, fixation and the like of ionic substances and physiologically active substances. The purpose is.

The present invention also provides a novel soluble aminomethylated aromatic polysulfone polymer useful as a treatment material for adsorption, separation, fixation and the like of ionic substances and physiologically active substances, or a molded product thereof. It is intended to provide a method.

[0011]

The present invention which achieves such an object comprises the following technical means (1) to (6). (1) An aromatic nucleus in which a group represented by the following general formula (I) (wherein R represents a hydrogen atom, a lower alkyl group or a benzyl group) is introduced as a side chain into the main chain polysulfone. An aromatic polysulfone polymer or a molded product thereof. _{R-NH-CH 2 - (} I)

(2) The aromatic polysulfone polymer having a side chain introduced therein is soluble, or the aromatic polysulfone polymer described in (1) above or a molded product thereof.

(3) The aromatic polysulfone polymer of the above (1) or a molded article thereof, wherein the main chain aromatic polysulfone is poly (p-phenylene ether sulfone).

(4) The aromatic polysulfone polymer of the main chain is Udel polysulfone, or the aromatic polysulfone polymer described in (1) above, or a molded product thereof.

(5) The aromatic polysulfone polymer described in (1) above, wherein the molded product is a petri dish, a bottle, a membrane, a fiber, a hollow fiber, a granular product, or an assembled product using these. The molded product.

(6) The aromatic polysulfone polymer or the molded product thereof according to (1), wherein the acylamidomethylated aromatic polysulfone polymer or the molded product thereof is hydrolyzed in the presence of an acid catalyst. Manufacturing method.

Next, the present invention will be described in more detail. The aromatic polysulfone polymer referred to in the present invention may be any polysulfone polymer having an aromatic nucleus and a sulfonyl group in the main chain and is not particularly limited, but specific examples thereof include poly (p - phenylene ether sulfone): - {(p-C 6 H 4) -SO 2 - (p
_{-C 6 H 4) -O-} n} - or, Udel-polysulfone _{:-( p-C 6 H 4)} -SO 2 - (p-C 6 H 4) -
_{O- (p-C 6 H 4} ) -C (CH 3) 2 - (p-C 6 H
₄₎ -O} _n - _{other, - (p-C 6 H} 4) -SO 2 -
_{(P-C 6 H 4)} -O- (p-C 6 H 4) -O} n -,
_{- {(p-C 6 H} 4) -SO 2 - (p-C 6 H 4) -S
_{- (p-C 6 H 4} ) -O} n -, - {(p-C 6 H 4)
_{-SO 2 - (p-C 6} H 4) -C (CF 3) - (p-C
_{6 H 4) -O- (p-} C 6 H 4) -O} n - like structure may be mentioned polymers with the.

Specific examples of the group represented by the general formula (I) in the present invention include aminomethyl group, N-methylaminomethyl group, N-ethylaminomethyl group, N-propylaminomethyl group and N- Examples thereof include a butylaminomethyl group and an N-benzylaminomethyl group, but are not limited thereto. However, in particular, the aminomethyl group having no substituent has less non-specific adsorption and less steric hindrance, and is therefore suitable for immobilizing a physiologically active substance.

The appropriate amount of these groups varies depending on the chemical structure of the polymer and the use, but it is usually 0.001 to 4 per repeating unit. Those having a large amount of aminomethyl groups are suitably used for adsorption, and those having a small amount of aminomethyl groups are suitably used for immobilization.
Those having a large amount of aminomethyl groups are well soluble in dimethyl sulfoxide in the form of hydrochloride, but are hardly soluble in general organic solvents. However, in the form of dehydrochlorinated free amine, it has the property of being well soluble in aprotic polar solvents such as N, N-dimethylformamide, N, N-dimethylformamide and dimethylsulfoxide as well as chlorine-based solvents such as methylene chloride. Have.

As described above, according to the present invention, a polymer having appropriate characteristics can be obtained by adjusting the amount of aminomethyl group. Therefore, the amount of aminomethyl group introduced depending on the purpose of use. Should be adjusted appropriately.

The acylamidomethylated aromatic polysulfone polymer referred to in the present invention means an aromatic polysulfone polymer having an aromatic nucleus in which an acylamidomethyl group is introduced as a side chain into a main chain polysulfone. Examples of the group include formyl, acetyl, chloroacetyl, trichloroacetyl, phthalyl groups and the like.
A chloroacetyl group is preferably used because it is easily available and has a high hydrolysis rate. The acylamide methylated aromatic polysulfone polymer is usually obtained by converting polysulfone into a haloacylamide methylating agent under a sulfuric acid catalyst,
For example, it can be obtained by treating with an N-methylol compound such as N-methylol-α-chloroacetamide.
That is, it is achieved by adding a mixed solution of a haloacyl amide methylating agent, an acid catalyst, and a solvent to a solution of aromatic polysulfone.

In the present invention, the acid catalyst used for hydrolyzing the acylamide methylated aromatic polysulfone polymer or its molded product may be a mineral acid such as hydrochloric acid or sulfuric acid, but is not limited to these. As long as it has the same effect, an appropriate one is used. Water is used as a solvent for the reaction, but the reaction is promoted when nitrobenzene, tetrachloroethane, or the like, which is a solvent for the polymer, coexists.

The aromatic polysulfone polymer of the present invention or a molded article thereof is produced by mixing a mixed solution of an acylamidomethylated aromatic polysulfone polymer, an acid catalyst and a solvent at room temperature to 200 ° C., especially 80 to 1 at 150 ° C
Achieved by heating for ~ 20 hours.

The form of the molded article of the present invention is petri dish, bottle,
The tube, the membrane, the fiber, the hollow fiber, the granular material, or an assembly using these materials, or any material equivalent thereto, is not particularly limited.

The molded article of the aromatic polysulfone of the present invention is prepared by using an aromatic polysulfone polymer having a side chain introduced therein by a suitable method such as a petri dish, a bottle, a film, a fiber, a hollow fiber, or a granular form. Is it manufactured by molding into
Alternatively, it is produced by introducing a side chain into a molded product of an appropriate form made of an aromatic polysulfone having a main chain. The molding may be appropriately carried out by an ordinary method using an ordinary molding method, and is not particularly limited.

The polymer of the present invention or a molded article thereof can be used as it is or after immobilizing a physiologically active substance, that is, for example, protein, amino acid,
Immobilize substances such as peptides, such as enzymes (glucuronidase), growth factors (EGF, FGF, etc.), antibodies, etc., and process them into products of appropriate shapes such as cell culture instruments, artificial organs, artificial blood vessels, catheters, etc. It can be used for things such as doing.

[0027]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to the examples. The evaluation methods in the examples were as follows.

1. Infrared absorption spectrum A Shimadzu Fourier transform infrared spectrophotometer FTIR-4300 was used and molded into a film or a KBr tablet for measurement.

2. Measurement of ion exchange capacity (amount of amino group) 0.1 to 1 g of a finely ground polymer sample was packed in a column and regenerated by flowing 5% diisopropylethylamine / methanol. Methanol, a 0.1 M solution of picric acid in methanol, and methanol were sequentially flowed, and then 0.
Pour a 1M diisopropylethylamine / methanol solution and measure the absorbance (360 mμ) of the eluate.
The amount of tertiary amino groups was determined.

[Example 1] A mixed solution of 114 ml of nitrobenzene and 227 ml of sulfuric acid was cooled to 0 ° C to obtain 22.7 g.
N-methylol-α-chloroacetamide was added to
It melt | dissolved at -10 degreeC and the amide methylation liquid was prepared.

50 g of Udel polysulfone (P35
00) was dissolved in 500 ml of nitrobenzene, the above-mentioned amidomethylated solution heated to 10 ° C was added with vigorous stirring, and the mixture was stirred at 15 ° C for 2 hours. Then, the reaction solution was poured into 5 L of methanol at -20 ° C, and the precipitated polymer was washed with methanol and dried to obtain 64.4 g of chloroacetamidomethylated polysulfone. This polymer has an infrared absorption spectrum of 1672 cm ^-1 (amide-I), 1528 cm ^-1 (amide-II) and 336.
The structure was confirmed because strong absorption of an amide group was observed at 2 cm ^-1 (N-H).

11.0 g of the obtained amidomethylated polymer
Was heated under reflux in 150 ml of 6N hydrochloric acid for 7 hours.
The polymer was washed with water to obtain 9.85 g of a polymer of the present invention, aminomethylated polysulfone hydrochloride. This polymer has the property of being soluble in dimethyl sulfoxide, but insoluble in methylene chloride or N, N-dimethylformamide. It became insoluble in methylene chloride but soluble in methanol and hot water. A tough film was obtained from the dimethylsulfoxide solution. Ion exchange capacity is 2.0
It was milliequivalent / g. 167 in infrared absorption spectrum
0 cm ^-1 absorption (amide -I) and 1528cm ^-1 (amide -II) disappeared, and its structure was confirmed from the fact that the absorption of ammonium groups appeared 2500~3600cm ^-1.

When this polymer was washed with a 50% dimethylamine aqueous solution, it was confirmed that it was dehydrochlorinated, and it became soluble in methylene chloride and N, N-dimethylformamide in addition to dimethyl sulfoxide.

Example 2 A mixed solution of 19 ml of nitrobenzene and 38 ml of sulfuric acid was cooled to 0 ° C. and 3.75 g of N 2 was added.
-Methylol-α-chloroacetamide was added, 0-1
It melt | dissolved at 0 degreeC and the amide methylation liquid was prepared.

30 g of Udel polysulfone (P35
00) was dissolved in 300 ml of nitrobenzene, the above-mentioned amidomethylated solution heated to 10 ° C was added with vigorous stirring, and the mixture was stirred at 15 ° C for 2 hours. Then, the reaction solution was poured into 3 L of methanol at -20 ° C, and the precipitated polymer was washed with methanol and dried to obtain 32.9 g of chloroacetamidomethylated polysulfone. This polymer had an infrared absorption spectrum of 167 as in Example 1.
6 cm ^-1 (amide -I) and 3,367 cm ^-1 (N-
In (H), strong absorption of an amide group was recognized, and 1.60% of nitrogen was recognized by elemental analysis.

11.0 g of the obtained amidomethylated polymer
Was heated under reflux in 150 ml of 6N hydrochloric acid for 7 hours.
The polymer was washed with water to obtain 9.85 g of a polymer of the present invention, aminomethylated polysulfone hydrochloride. This polymer has the property of being soluble in dimethyl sulfoxide, but insoluble in methylene chloride or N, N-dimethylformamide. It became insoluble in methylene chloride but soluble in methanol and hot water. A tough film was obtained from the dimethylsulfoxide solution. Ion exchange capacity is 0.8
It was milliequivalent / g. 167 in infrared absorption spectrum
0 cm ^-1 absorption (amide -I) and 1528cm ^-1 (amide -II) disappeared, and its structure was confirmed from the fact that the absorption of ammonium groups appeared 2500~3600cm ^-1.

When this polymer was washed with a 50% dimethylamine aqueous solution, it was confirmed that it was dehydrochlorinated, and it became soluble in methylene chloride and N, N-dimethylformamide in addition to dimethylsulfoxide.

Example 3 20 g of 2.0 g of the chloroacetamidomethylated polysulfone polymer obtained in Example 2 was used.
It was dissolved in N, N-dimethylformamide (ml) and cast on a glass plate to prepare a tough film having a thickness of 70 μm. The mixture was heated under reflux in 150 ml of 6N hydrochloric acid for 7 hours. The film was washed with water, dried, and confirmed to be hydrolyzed by infrared absorption spectrum. No reduction in film strength was observed.

Example 4 40 g of 5.0 g of the chloroacetamidomethylated polysulfone polymer obtained in Example 2 was used.
It was dissolved in N, N-dimethylformamide (ml) and cast on a glass plate to prepare a tough film having a thickness of 70 μm. This film (4 cm x 5 cm) was mixed with 16 ml of a solution of Salmonella minnesota Re595LPS (20 μg /
ml), 80 mg of 1-ethyl-3,3-dimethylaminopropylcarbodiimide hydrochloride was added, and the mixture was shaken at room temperature for 72 hours. The film was washed with water to obtain an LPS-immobilized polysulfone film. LPS concentration in the mother liquor measured by the phenol / sulfuric acid method was 12 μg / ml
Therefore, it was found that the immobilized amount was 128 μg.

Similarly, according to a conventional method, a petri dish, a bottle,
When a membrane, a fibrous shape, a hollow fiber and a granular material were produced, a corresponding molded product was obtained.

[0041]

INDUSTRIAL APPLICABILITY As described above in detail, the present invention introduces a specific aminomethyl group as a side chain into a main chain aromatic polysulfone, thereby providing a novel soluble aromatic polysulfone having excellent properties. The greatest feature is to obtain a polymer or a molded product thereof, and the aromatic polysulfone polymer obtained by the present invention is used as a treatment material for adsorption, separation, fixation, etc. of ionic substances and physiologically active substances. It is useful.

In addition, the reactivity of the aromatic polysulfone polymer of the present invention can be appropriately adjusted by adjusting the kind and amount of the aminomethyl group introduced as a side chain. It has an advantage that a treating material having appropriate reaction characteristics can be easily and surely performed.

Further, the aromatic polysulfone polymer is
Suitable as materials for affinity chromatography adsorbents, therapeutic blood treatment agents, antibacterial materials, etc. in the form of petri dishes, bottles, membranes, fibers, hollow fibers, granules, or molded products such as assembled products using these. Can be used.

Claims (6)

[Claims] 1. A fragrance in which a group represented by the following general formula (I) (wherein R represents a hydrogen atom, a lower alkyl group or a benzyl group) is introduced as a side chain into a main chain polysulfone. Aromatic polysulfone polymer having a nucleus or a molded product thereof. _{R-NH-CH 2 - (} I) 2. The aromatic polysulfone polymer according to claim 1, wherein the side chain-introduced aromatic polysulfone polymer is soluble, or a molded product thereof. 3. The main chain aromatic polysulfone is poly (p
-Phenylene ether sulfone), the aromatic polysulfone polymer according to claim 1, or a molded article thereof. 4. The aromatic polysulfone polymer according to claim 1, or a molded product thereof, wherein the main chain aromatic polysulfone is Udel polysulfone. 5. The aromatic polysulfone polymer or its molding according to claim 1, wherein the molded product is a petri dish, a bottle, a membrane, a fiber, a hollow fiber, a granular product or an assembled product using these. Goods. 6. The production of an aromatic polysulfone polymer or a molded product thereof according to claim 1, wherein the acylamidomethylated aromatic polysulfone polymer or a molded product thereof is hydrolyzed in the presence of an acid catalyst. Method.