JPH09227682A - Polysulfone polymer and its preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To produce a polysulfone polymer which has a novel polyaminoalkylene group in its side chain and is useful as a material for treatments of an ionic material or a physiologically active material, such as adsorption, separation, or immobilization, and to provide a process for preparing the same. SOLUTION: This polysulfone polymer comprises: a main chain of an arom. polysulfone, and a side chain functional group introduced into the main chain, the side chain functional group being a group represented by formula (I): E-CH(R 1)-CO-N(R2)-CH2 (wherein E represents a poly(aminoalkylene) group, R1 and R2, which may be the same or different, represent a hydrogen atom or a 1-5C alkyl group). The process for preparing an arom. polysulfone polymer comprises reacting an arom. polysulfone polymer, substd. with a halogen substituent group represented by formula (II): X-CH(R<1> )-CO-N(R<2> )-CH2 (wherein X represents a halogen atom), with a polyamine compd.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a polysulfone polymer having an aromatic nucleus having a poly (alkylamine) residue group introduced as a graft group as a side chain, and a method for producing the same, more specifically, an ionic substance. The present invention relates to a poly (alkylamine) -grafted aromatic polysulfone polymer that can be suitably used for adsorption, separation, immobilization of a physiologically active substance or the like, and a method for producing the same.

[0002]

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

Cellulose, agarose, polystyrene and the like have long been known as insoluble carriers used for immobilization, but these exist as insoluble molded articles. Since polysulfone has good moldability and can be used as a hollow fiber for dialysis, when a reactive functional group that can be used for immobilization, particularly an amino group, is introduced, its utility value is high. Therefore, chloromethylated polysulfone {Higuchi et al. J. Appl. Polymer C
hem. 46 , 449-457 (1992)} and amidomethylated polysulfone (JP-A-6-500925).

However, since polysulfone maintains its high mechanical properties due to the cohesive force of the polymer main chain, if too many functional groups are introduced into the main chain, its excellent mechanical properties will be lost. . On the other hand, if the introduction density of the functional groups is too low, there is a dilemma in which the adsorptivity is too low to achieve the purpose.

[0005]

DISCLOSURE OF THE INVENTION In view of the above problems of the prior art, the present inventors have made various studies on whether a simple method can be used to obtain polysulfone having a useful reactive functional group introduced in a sufficient amount. As a result, we succeeded in preparing an acetamidomethylated polysulfone grafted with polyamine which has a reaction property, is soluble and has a film-forming property, and gives a good film,
The present invention has been reached.

[0006]

The present invention has the following configuration to achieve the above object.

"(1) In the main chain aromatic polysulfone, a group represented by the following general formula (I) as a side chain functional group (provided that
In the formula, E represents a poly (aminoalkylene) group, R1 and R2 represent a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, and R1 and R2 may be the same or different. } The polysulfone polymer characterized by being introduced.

[0008] E-CH (R1) -CO- N (R2) -CH 2 - (I) (2) halogen-substituted group represented by the following general formula (III) (In the formula, X is a halogen atom The method for producing an aromatic polysulfone polymer according to claim 1, wherein the aromatic polysulfone polymer substituted with (1) is reacted with a polyamine compound.

X-CH (R ¹ ) -CO-N (R ² ) -CH _2- (III) "

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION Next, the present invention will be described in detail.

The aromatic polysulfone polymer having an aromatic nucleus in which a group represented by the general formula (I) is introduced as a side chain in the present invention is a polysulfone polymer having an aromatic nucleus and a sulfonyl group in the main chain. Any aromatic ring having a substituent represented by the general formula (I) may be used without any particular limitation.

As a specific example of the aromatic polysulfone polymer, poly (p-phenylene ether sulfone) widely available on the market:-｛(p-C ₆ H ₄ ) -SO _{2-
(P-C 6 H 4)} -O-} n- and _{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) -O- (p-C
₆ H ₄ ) -C (CF ₃ ) _2- (p-C ₆ H ₄ ) -O _{} n-}
A polymer having a structure such as, wherein the aromatic nucleus is a group represented by the general formula (I), for example, diethylenetriamino-
Examples thereof include those substituted with an acetamidomethyl group, a triethylenetetraamino-acetamidomethyl group, a tetraethylenepentaamino-acetamidomethyl group, a poly (ethyleneimino) -acetamidomethyl group, or the like.

The group represented by formula (I) will be described in more detail. R1 and R2 are each a hydrogen atom, or a carbon atom such as a methyl group, an ethyl group, a propyl group or a butyl group.
~ 5 alkyl groups, R1 and R2 may be the same or different, but R2 is a hydrogen atom, especially R
It is preferable that both 1 and R2 are hydrogen atoms because they are most easily produced and have high reactivity.

The poly (aminoalkylene) group of E in the general formula (I) is a group represented by the following general formula (II) (wherein A1 and A2 are alkylene having 2 to 12 carbon atoms). Group, an alkylene group having 3 to 12 carbon atoms branched from a methyl group, and an alkylene group having 4 to 12 carbon atoms branched from an ethyl group, wherein A1 and A2 may be the same or different. Good, n is preferably an integer of 2 or more).

NH ₂ (A 1 -NH-A ₂ -NH) _n- (II) Examples of A 1 -NH-A _{2 in} the general formula (II) include ethyleneiminoethylene group and trimethyleneiminotrimethylene group. , Tetramethyleneiminotetramethylene group, hexamethyleneiminohexamethylene group, ethyleneiminotetramethylene group, ethyleneiminohexamethylene group, tetramethyleneiminohexamethylene group, ethyleneiminodecamethylene group and the like. When n in the general formula (I) of the side chain substituent is too small, the effect of the graft structure is difficult to be obtained, while when it is too large, excellent physical properties of polysulfone are hard to be expressed, and therefore 2 to
5000, especially 5-2000 are preferable. Also,
The relationship between the density of the group represented by the general formula (I) and n affects the performance of the polymer, and is preferably taken into consideration. That is,
When the density of the group represented by the general formula (I) is high, excellent physical properties of polysulfone cannot be maintained unless n is small. Therefore, n is preferably small, and when the density is low, n is small. If n is small, the effect of the graft structure is not obtained, so n is preferably large. This poly (aminoalkylene) group may be partially branched. These groups may be present alone or in plural depending on the purpose of use.

Further, when the poly (aminoalkylene) group of E in the general formula (I) is a polymer of ethyleneimine,
If the degree of polymerization is too low, the side chain functional group density must be increased in order to obtain the effect of the functional group, and the physical properties of the resulting product will be low, so the degree of polymerization is 4 or more. preferable. Further, if the degree of polymerization is too high, the viscosity of the product obtained is too high, or the processability is deteriorated due to hydrophilicity, so 4 or more and 10000 or less, especially,
It is preferably 10 or more and 4000 or less. The ethyleneimine polymer may be partially branched. These groups may be present alone or in combination depending on the purpose of use.

The group represented by the general formula (I) may be bonded to the main chain polysulfone at any position and is not particularly limited. However, since it is easy to introduce by a amide methylation reaction, the main chain ether can be introduced. It is easy to obtain the ortho position with respect to the group. For example, in Udel polysulfone synthesized from bisfur A and di (chlorophenyl) sulfone, it is easy to obtain a product having a group represented by the general formula (I) at the ortho position from the hydroxyl group of bisphenol A.

The content of the group represented by the general formula (I) in the polymer of the present invention is not particularly limited, and the density varies depending on the chemical structure and use of the polymer serving as the backbone, but if it is too small, On the other hand, if the function is difficult to be expressed, on the other hand, if it is too large, it tends to be difficult to form a tough film by itself, and when it is mixed with polysulfone, the compatibility with polysulfone becomes insufficient and the film does not work well. Since the film may not be formed, 0.0001 to 0.3 per repeating unit, especially 0.0
01 to 0.3 is preferable.

The production of the polymer of the present invention is easily accomplished by adding the corresponding polyamine to a solution of haloacetamidomethylated polysulfone and reacting at a temperature of about 0 to 100 ° C. The amount is not particularly limited,
In order to obtain a soluble polymer, it is desirable to use at least 2 times mol of the haloacetamidomethyl group. In particular, in the case of a branched polyamine, it is preferable to use a large excess of polyamine in order to obtain a soluble polymer.

Further, as a reaction solvent, tetrahydrofuran, dimethyl sulfoxide, N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone and the like are preferably used when the reaction is carried out in a homogeneous system. A method of surface-treating the polymer is also possible, and for that purpose, a solvent that does not dissolve polysulfone, such as water, methanol and ethanol, but dissolves polyamine is preferably used.

The polymer of the present invention can be used as an adsorbent by itself or as an intermediate for producing an adsorbent having a higher function, and can be used as a flat membrane or a hollow fiber membrane to separate various substances by filtration. -Used for concentration and immobilization of substances. In addition, applications to cell culture instruments, artificial organs, artificial blood vessels, catheters, and the like are conceivable. Examples of the substance to be immobilized include albumin, antibody protein, enzyme, growth factor (vascular endothelial cell growth factor, fibroblast growth factor, etc.), amino acid, peptide, polysaccharide and the like.

[0022]

EXAMPLES The present invention will be described in more detail below with reference to examples.

The evaluation method in this example was as follows.

1. Infrared absorption spectrum A Shimadzu Fourier transform infrared spectrophotometer FT-IR4300 was used to measure a film or a KBr tablet.

2. Amino group quantification 1 to 3 g of a sample was dissolved in 50 mL of tetrahydrofuran, a 5 to 20-fold molar acetic anhydride / pyridine (1/5) solution was added, and the mixture was allowed to stand at room temperature for 1 h. Using cresol red solution as an indicator,
Titrated with 5N NaOH. The difference from the blank was defined as the amount of amino groups.

Example 1 A mixed solution of 15 mL of nitrobenzene and 30 mL of sulfuric acid was added to 0.
After cooling to C, 4.1 g of N-methylol-α-chloroacetamide was added and dissolved, and then 360 mL of cold nitrobenzene was added thereto, and then a solution of 72 g of Udelpolysulfone P3500 dissolved in 360 mL of nitrobenzene was added. , With good stirring. Further, the mixture was stirred at room temperature for 3 hours. Thereafter, the reaction mixture was placed in a large excess of cold methanol to precipitate the polymer. The precipitate was thoroughly washed with methanol and then dried to obtain 74 g of α-chloroacetamidomethylated polysulfone (polymer-I). This polymer showed absorption of an amide group at 1670 cm ^-1 in an infrared absorption spectrum. Further, in elemental analysis, the nitrogen content is 0.9%, the chlorine content is 1.4%, and the substitution rate is 0.2%.

20 g of Polymer-I obtained above was added to 200 m
L was dissolved in dimethylformamide, and a solution of 40 mL of tetraethylenepentamine dissolved in 200 mL of dimethylformamide was added thereto, and the mixture was stirred at room temperature for 24 hours. The reaction mixture was put in a large excess of methanol to precipitate a polymer, and the precipitate was washed well with methanol and water and then dried to obtain 20 g of the polymer of the present invention. The infrared absorption spectrum of this polymer showed absorption of an amide group at 1674 cm ^-1 , and absorption of a methylene group (ethylenediamino group) at 2820 cm ^-1 and 2874 cm ^-1 . It dissolves well in tetrahydrofuran, chloroform and dimethylformamide. The amount of amino groups is 3.9 meq /
g.

A dimethylacetamide solution of this polymer was coated on glass and put in water to form a film. As a result, a semipermeable membrane having the same mechanical properties as polysulfone was obtained.

Example 2 A mixed solution of 8 mL of nitrobenzene and 15 mL of sulfuric acid was added at 0 ° C.
After cooling to 2.1 g (16 mmol) of N-methylol-α-chloroacetamide was added and dissolved, to which 9
After adding 0 mL cold nitrobenzene, 72 g (0.1
6 mol) Udel polysulfone P3500 360 m
A solution of L in nitrobenzene was added with good stirring. Further, the mixture was stirred at room temperature for 3 hours. Thereafter, the reaction mixture was placed in a large excess of cold methanol to precipitate the polymer. The precipitate was thoroughly washed with methanol and then dried to obtain 72 g of α-chloroacetamidomethylated polysulfone (Polymer-II). This polymer showed absorption of an amide group at 1670 cm ^-1 in an infrared absorption spectrum.

20 g of the polymer-II obtained above was added to 200 m
L was dissolved in dimethylformamide, and a solution of 40 ml of pentaethylenehexamine dissolved in 200 ml of dimethylformamide was added thereto, and the mixture was stirred at room temperature for 48 hours. The reaction mixture was put into a large excess of water to precipitate the polymer, and the precipitate was thoroughly washed with methanol and water and then dried to obtain 20 g of the polymer of the present invention. The infrared absorption spectrum of this polymer showed absorption of an amide group at 1674 cm ^-1 , and absorption of a methylene group (ethylenediamino group) at 2820 cm ^-1 and 2874 cm ^-1 . It dissolves well in tetrahydrofuran, chloroform and dimethylformamide. The amount of amino groups was 2.3 meq / g.

A dimethylacetamide solution of this polymer was applied onto glass, and was placed in water to form a film. As a result, a semipermeable membrane having the same mechanical properties as polysulfone was obtained.

Example 3 20 g of the polymer-II obtained in Example 2 was dissolved in 200 mL of tetrahydrofuran, and polyethyleneimine (average molecular weight 700: Aldrich Chemical Co.) 40 was added thereto.
A solution of g in 200 mL of tetrahydrofuran was added, and the mixture was stirred at room temperature for 48 hours. The reaction mixture was put in a large excess of methanol to precipitate a polymer, and the precipitate was washed well with methanol and water and then dried to obtain 20 g of the polymer of the present invention. This polymer was well soluble in dimethylformamide, and the amount of amino groups was 1.9 meq / g.

Example 4 A mixed solution of 21 mL of nitrobenzene and 42 mL of sulfuric acid was added to 0.
After cooling to ℃, 5.7 g of N-methylol-α-chloroacetamide was added and dissolved, and 16 mL of this was taken, and
80 mL of cold nitrobenzene was added. 2 parts of this liquid (11 mmol of N-methylol-α-chloroacetamide)
00 g (0.45 mol) of Udel Polysulfone P35
00 in a solution of 360 mL of nitrobenzene,
Add with good stirring. Further, the mixture was stirred at room temperature for 3 hours. Thereafter, the reaction mixture was placed in a large excess of cold methanol to precipitate the polymer. The precipitate was thoroughly washed with methanol and then dried to obtain 200 g of α-chloroacetamidomethylated polysulfone (polymer-III). This product showed absorption of an amide group at 1678 cm ^-1 in an infrared absorption spectrum.

20 g of Polymer-III obtained above was added to 200 m
L was dissolved in dimethylformamide, and a solution of 40 ml of pentaethylenehexamine dissolved in 200 ml of dimethylformamide was added thereto, and the mixture was stirred at room temperature for 48 hours. The reaction mixture was put into a large excess of water to precipitate the polymer, and the precipitate was washed well with methanol and water and then dried to obtain 20 g of the polymer of the present invention. The infrared absorption spectrum of this polymer showed absorption of an amide group at 1674 cm ^-1 , and absorption of a methylene group (ethylenediamino group) at 2820 cm ^-1 and 2874 cm ^-1 . It dissolves well in tetrahydrofuran and dimethylformamide. A solution of this polymer in dimethylacetamide was coated on glass, and the film was placed in water to form a film. As a result, a semipermeable membrane having the same mechanical properties as that of polysulfone was obtained.

Example 5 20 g of the polymer-III obtained in Example 4 was dissolved in 200 mL of dimethylformamide, and 40 g of polyethyleneimine (average molecular weight 700: Aldrich Chemical Co.) was added thereto.
A solution prepared by dissolving g in 200 mL of dimethylformamide was added, and the mixture was stirred at room temperature for 48 hours. The reaction mixture was put into a large excess of methanol to precipitate a polymer, and the precipitate was washed well with methanol and water and then dried to obtain 20 g of the polymer of the present invention. This polymer shows an amide group absorption at 1674 cm ^-1 in the infrared absorption spectrum,
And an absorption of the methylene groups (ethylene diamino group) to 0 cm ^-1 and 2874cm ^-1. This is tetrahydrofuran,
Soluble in chloroform and dimethylformamide. The amount of amino groups was 1.4 meq / g. A solution of this polymer in dimethylacetamide was coated on glass, and the film was placed in water to form a film. As a result, a semipermeable membrane having the same mechanical properties as that of polysulfone was obtained.

Example 6 20 g of the polymer-III obtained in Example 4 was dissolved in 200 mL of tetrahydrofuran, and a solution of 40 g of polyethyleneimine (average molecular weight 10,000: Polyscience Co.) in 200 mL of tetrahydrofuran was added thereto, and the mixture was allowed to stand at room temperature. It was stirred for 48 hours. The reaction mixture was put into a large excess of water to precipitate the polymer, and the precipitate was thoroughly washed with water and then dried to obtain 20 g of the polymer of the present invention. The infrared absorption spectrum of this polymer showed absorption of an amide group at 1674 cm ^-1 , and absorption of a methylene group (ethylenediamino group) at 2820 cm ^-1 and 2874 cm ^-1 . It dissolves well in tetrahydrofuran and dimethylformamide. The amount of amino groups was 2.5 meq / g. A solution of this polymer in dimethylacetamide was coated on glass, and the film was placed in water to form a film. As a result, a semipermeable membrane having the same mechanical properties as that of polysulfone was obtained.

Example 7 20 g of the polymer-III obtained in Example 4 was dissolved in 200 mL of dimethylformamide, and polyethyleneimine (average molecular weight 70000: 30% aqueous solution of Wako Pure Chemical Industries, Ltd.) was concentrated under reduced pressure to remove water. A solution of 40 g in 200 mL of dimethylformamide was added, and the mixture was stirred at room temperature for 48 hours.
Stirred for hours. The reaction mixture was put into a large excess of saturated saline, the polymer was precipitated, and the precipitate was thoroughly washed with water and then dried to obtain 16 g of the polymer of the present invention. The infrared absorption spectrum of this polymer showed absorption of an amide group at 1674 cm ^-1 , and absorption of a methylene group (ethylenediamino group) at 2820 cm ^-1 and 2874 cm ^-1 . It dissolves well in tetrahydrofuran and dimethylformamide.
The amount of amino groups was 0.84 meq / g. A solution of this polymer in dimethylacetamide was coated on glass, and the film was placed in water to form a film. As a result, a semipermeable membrane having the same mechanical properties as that of polysulfone was obtained.

[0038]

INDUSTRIAL APPLICABILITY As described above in detail, the present invention introduces a specific polyamine graft group as a side chain into a main chain aromatic polysulfone, thereby improving the solubility of the novel aromatic polysulfone polymer. The greatest feature is to obtain a coalesced product, and the aromatic polysulfone polymer obtained by the present invention is useful as a treatment material for adsorption, separation, fixation and the like of ionic substances and physiologically active substances.

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

Claims (9)

[Claims] 1. A group represented by the following general formula (I) as a side chain functional group in the main chain aromatic polysulfone (wherein,
E represents a poly (aminoalkylene) group, R1 and R
2 represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, and R1 and R2 may be the same or different. } The polysulfone polymer characterized by being introduced. E-CH (R1) -CO- N (R2) -CH 2 - (I) 2. The E in the general formula (I) is represented by the following general formula (I
A group represented by I) (wherein A1 and A2 have 2 carbon atoms)
~ 12 alkylene groups, methyl group branched carbon number 3 ~
At least one selected from a alkylene group having 12 carbon atoms and an alkylene group having 4 to 12 carbon atoms in which an ethyl group is branched is shown. A1 and A2 may be the same or different. n
Indicates an integer of 2 or more. 2. The polysulfone polymer according to claim 1, wherein _{NH 2 (A1 -NH-A2 -NH} ) n - (II) 3. The polysulfone polymer according to claim 1, wherein the poly (aminoalkylene) group in the general formula (I) is a polymer of ethyleneimine having a polymerization degree of 4 or more and 10000 or less. 4. The polysulfone polymer according to claim 1, wherein the aromatic polysulfone is poly (p-phenylene ether sulfone). 5. The aromatic polysulfone has the chemical formula-{(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
The polysulfone polymer according to claim 1, which is a polysulfone represented by-. 6. The polysulfone polymer according to claim 1, wherein the side chain functional group is substituted at a density of 0.0001 to 0.3 per polysulfone repeating unit. 7. The n in the general formula (II) is 2 or more and 5000.
The polysulfone polymer according to claim 2, wherein: 8. The polysulfone polymer according to claim 1, which is soluble in an organic solvent. 9. An aromatic polysulfone polymer substituted with a halogen substituent represented by the following general formula (III) (wherein X represents a halogen atom) is reacted with a polyamine compound. The method for producing an aromatic polysulfone polymer according to claim 1. ^{X-CH (R 1) -CO} -N (R 2) -CH 2 - (III)