JPH111554A - Polyhydroxyether resin and its synthesis and polyhydroxyether membrane and its production - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject resin excellent in mechanical properties, low in surface tension, and useful as a material for e.g. artificial pulmonary membrane by reacting an epihalohydrin with a bisphenol having specific structure in an aprotic polar solvent. SOLUTION: At least one kind of bisphenol having structure of formula I (X is a group of formula II, etc.; Y is H, etc.; (m) is an integer of 1-4), an epihalohydrin at a molar ratio thereto of 0.95-1.05, and at least equimolar amount of sodium hydroxide's aqueous solution are added to an aprotic polar solvent, and the resulting system is homogeneously agitated at a reaction temperature not lower than room temperature but not higher than the boiling point of the operatic polar solvent, thus obtaining the objective resin shown pref. by formula III ((1) is a number of >=1), free from any insoluble and infusible gel, containing 20-100 mol.% of R group of formula IV with the remaining R group shown by formula I, etc., and having a reduced viscosity at 25 deg.C of >=0.6 (dL/g).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a polyhydroxyether resin, a method for synthesizing the same, a polyhydroxyether film and a method for producing the same.

[0002]

2. Description of the Related Art Advances in medical technology in recent years have made it possible to treat heart diseases such as coronary artery bypass surgery as well as heart transplantation. Takes time. After surgery, extracorporeal circulation extends for a long time until the heart is removed from the heart-lung machine.

At present, a commercially available artificial lung used for open heart surgery uses a silicon homogeneous membrane or a porous membrane. A gas is exchanged by dissolving and diffusing gas molecules into the silicon homogenous membrane, so that the silicon homogeneous membrane has an extremely small gas permeation amount, and particularly has insufficient carbon dioxide gas permeation performance. In addition, polytrimethylsilylpropyne homogenous membranes, which have higher gas permeability than silicon homogenous membranes, and non-porous membranes made of fluorinated polyimide used for gas separation membranes, have a low gas permeability as an artificial lung membrane. It is enough. On the other hand, with a porous artificial lung membrane,
Since gas exchange is performed through pores of about 0 ° to 2000 °, the gas permeation amount is large.

[0004] However, during prolonged extracorporeal circulation, adsorption of plasma proteins into the pores of the artificial lung membrane occurs, and the pore walls become hydrophilic. Therefore, a plasma leak occurs, the gas exchange ability is reduced, or replacement of the artificial lung membrane is required, and the burden on the patient is increased, healing is delayed, and it is difficult to withdraw from the heart-lung machine.

[0005] The cause of the above-mentioned plasma leak is closely related to the contact angle of the membrane material with the plasma. When the pores are regarded as capillaries as shown below, if the contact angle with plasma is 90 ° or more, the surface tension F acting between the pore walls acts in a direction to suppress the invasion of plasma.

[0006]

(Equation 1)

[0007] Various membrane materials have been tried to suppress plasma leak.

For example, as materials having high hydrophobicity, polypropylene (PP, JP-A-54-160098), polytetrafluoroethylene (PTFE, JP-A-60-53153) and poly (4-methylpentene-1) ( PMP, JP-A-1-10427
Porous artificial lung membranes using hydrophobic materials such as No. 3) were studied. However, even with these materials, plasma proteins smaller than the pores were found in the pores of the porous membranes with pore diameters of several hundred mm or more. Therefore, it is impossible to avoid plasma leak in long-term extracorporeal circulation.

An ultrafiltration membrane having a molecular weight cut off of about 10,000 to 50,000, which is composed of an asymmetric non-porous membrane having a pore diameter of several hundreds of degrees or less (hereinafter asymmetric membrane), is a plasma protein such as albumin or γ-
Since it does not transmit globulin, it is considered that plasma leak can be suppressed. The PP, PTFE,
Since neither PMP nor silicone resin is soluble in general organic solvents, it is difficult to obtain an asymmetric membrane having the same structure as the ultrafiltration membrane.

Polysulfone is a material which is dissolved in an organic solvent and has high hydrophobicity. Polysulfone is converted to N-methyl-2-pyrrolidone (NMP) or N, N-dimethylacetamide
A solution prepared by dissolving in a polar solvent such as (DMAc) and adding an appropriate additive is subjected to a wet film-forming method or a dry-wet film-forming method. A film is obtained. This membrane has already been put to practical use in medical applications such as ultrafiltration membranes, hemodialysis membranes, and plasma concentration membranes.

As an artificial lung using this asymmetric polysulfone membrane, an asymmetric polysulfone membrane having high gas permeability (Japanese Patent Laid-Open No. 61-119272) has also been proposed. However, since the polysulfone membrane has a contact angle with water of 90 ° or less, it is impossible to suppress water intrusion. For this reason, water from which high molecular weight components have been removed from the plasma by ultrafiltration may block the pores, and the gas exchange capacity of the oxygenator may be reduced.

As described above, in order to solve the problem of plasma leak, a material having a high hydrophobicity and a contact angle larger than that of the plasma is used as the membrane material, and the membrane has a pore diameter at which plasma proteins cannot enter the pores. There was a need for an asymmetric membrane. Further, not only in the heart-lung machine, but also in a hemodialysis machine, a blood transfusion or a blood collection machine, a blood circuit in which prevention of blood coagulation and suppression of complement activation are essential in order to maintain a therapeutic effect.

On the other hand, polyhydroxyether resins (phenoxy resins) obtained from diphenol and epihalohydrin have been studied for many years, and more than 30 years have already passed since they were put into practical use as thermoplastic resins.

For example, as a method of synthesizing a phenoxy resin from bisphenol A and epichlorohydrin, Carpen
ter, including the method presented in USP 2,602,075, Wynstra proposed synthesis in ethanol (USP 3,305,528) and D
Synthesis in MSO (US Pat. No. 3,277,051), Roicki (eg, Maklo
mol. Chem. 179,1661 (1978) or 181, 985 (1980)).

In order to improve mechanical properties and the like, a method for synthesizing a phenoxy resin such as methylene bisphenol, ethylidene bisphenol, dihydroxyphenyl sulfone or the like as a diphenol has also been reported.

Of the diphenols, 2,2- (4
-Hydroxyphenyl) hexafluoroisopropylidene (bisphenol AF) is a diglycidyl ether
(Polymer letters, 3, 1021 (1965)). It has been reported that the epoxy cured product of diglycidyl ether of bisphenol AF is improved in glass transition temperature (Tg) and lowered in surface tension due to two trifluoromethyl groups (Japanese Patent Publication No. 61-44969).

However, although a low molecular weight polyhydroxyether resin having a degree of polymerization of 20 or less (eg, EP0212319A2) has been reported, a high molecular weight polyhydroxyether resin has not been reported. This is because the trifluoromethyl group having a high electron-withdrawing property increases the acidity of the phenolic hydroxyl group, and as a result, the nucleophilic reactivity to epichlorohydrin decreases, so that a high molecular weight polymer cannot be obtained.

[0018]

Therefore, the present invention provides a reduced viscosity of 0.6 (dl / g) or more, excellent mechanical properties, low surface tension, and a plasma or plasma contact angle smaller than the contact angle with water. It is an object of the present invention to provide a polyhydroxyether resin having a specificity that a contact angle with a protein aqueous solution is larger and a contact angle with water is 90 ° or more, and a method for synthesizing the same.

Another object of the present invention is to provide a polyhydroxyether membrane which suppresses plasma leak and has a sufficient gas permeability, and a method for producing the same.

[0020]

The present invention is achieved by the following means.

(1) A polyhydroxyether resin not containing an insoluble and infusible gel represented by the formula (1),

Embedded image In the polyhydroxyether resin, the R group represented by the formula (2) is 100 mol% to 20 mol%, and the formula (2)

Embedded image The remaining R groups are any of the groups of R groups represented by formula (3),

Embedded image N, N- is added to 0.5 g of the polyhydroxyether resin.
Polyhydroxyether resin characterized by having a reduced viscosity at 25 ° C of 0.6 (dl / g) or more at 25 ° C of a solution made up to 100 ml by adding dimethylacetamide.

(2) The polyhydroxyether according to (1), wherein the remaining R groups of the polyhydroxyether resin are any one of a group of R groups represented by formula (4). Ether resin formula (4)

Embedded image

(3) The poly (2) according to (1) or (2), wherein the angle of contact with plasma or aqueous protein solution is larger than the angle of contact with water, and the angle of contact with water is 90 ° or more. Hydroxy ether resin

(4) At least one bisphenol having any of the structures represented by the formula (5) and epihalohydrin are added to an aprotic polar solvent and reacted. Method for synthesizing polyhydroxyether resin to be reacted Formula (5)

Embedded image

(5) In the aprotic polar solvent, at least one kind of bisphenol having any one of the structures represented by the formula (5) is added, and the molar ratio to the bisphenol is 0. .95 to 1.05 of epihalohydrin and an aqueous solution of sodium hydroxide in an equimolar amount or more with respect to the bisphenols, and uniformly stirring at a reaction temperature not lower than room temperature and not higher than the boiling point of the aprotic polar solvent. The method for synthesizing the polyhydroxyether resin according to (4), which is characterized in that:

(6) The aprotic polar solvent is dimethyl sulfoxide, N, N-dimethylacetamide, tetrahydrofuran, dioxane, N-methylpyrrolidone, N, N-
The method for synthesizing a polyhydroxyether resin according to (4) or (5), wherein the resin is one of dimethylformamide and sulfolane or a mixed solvent thereof.

(7) A polyhydroxyether film represented by the formula (1), wherein

Embedded image In the polyhydroxyether film, the R group represented by the formula (2) is 100 mol% to 20 mol%, and the formula (2)

Embedded image The remaining R groups are any of the groups of R groups represented by formula (3),

Embedded image N, N-dimethylacetamide is added to 0.5 g of the polyhydroxyether film and dissolved to make 100 ml, and the reduced viscosity at 25 ° C. is 0.6 (dl / g) or more. Hydroxy ether membrane

(8) The polyhydroxyether according to (1), wherein the remaining R groups of the polyhydroxyether film are any of the group of R groups represented by the formula (4). Ether film formula (4)

Embedded image

(9) A polyhydroxyether resin not containing an insoluble and infusible gel represented by the formula (1), dimethyl sulfoxide, N, N-dimethylacetamide, N-methyl-2-
A solution prepared by dissolving pyrrolidone, N, N-dimethylformamide, THF, acetone, sulfolane or a mixed solvent thereof and water, a salt, a low molecular weight compound or a high molecular weight compound as a third component and dissolving the same. A method for producing a polyhydroxyether film, characterized by being produced by a dry-wet method or a wet film-forming method using

Embedded image However, the R group represented by the formula (2) is 100 mol% to 20 mol.
%, And equation (2)

Embedded image The remaining R groups are any of the groups of R groups represented by formula (3):

Embedded image

(10) When the salt, low molecular weight compound or high molecular weight compound is NaCl, LiCl, CaCl ₂ , MgCl ₂ , Mg (ClO
₄ ) ₂ , LiClO ₄ , methanol, ethanol, propanol, ethylene glycol, diethylene glycol, propylene glycol, glycerin, urea, polypropylene glycol, polyethylene glycol, polyvinylpyrrolidone, polyacrylic acid, polyacrylamide, or a mixture thereof The method for producing a polyhydroxyether film according to (9), wherein the third component is 5 wt% to 50 wt% in the film forming solution.

[0031]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail.

In the present invention, the reduced viscosity is determined by adding a solution of N, N-dimethylacetamide to 0.5 g of a polyhydroxyether resin and dissolving the solution to 100 ml, and using a thermostat at 25 ° C. (Coolnics circulators CTR-22WS and CTE-C). twenty two
WS, manufactured by Yamato Scientific Co., Ltd.) and placed in an aquarium with an Ubbelohde viscometer (Shibata Scientific Instruments Co., Ltd., 1-5c)
St measurement), and was determined as η from the following equation.

[0033]

(Equation 2)

First, the polyhydroxyether resin of the present invention will be described.

The reduced viscosity of the polyhydroxyether resin of the present invention is preferably 0.6 (dl / g) or more, and a polymer having a reduced viscosity of 0.6 or more has high strength and toughness. A polymer having a reduced viscosity of less than 0.6 is hard and brittle, and it is difficult to maintain the shape.

By introducing the structure of the formula (2), it is possible to improve Tg and lower the surface tension as compared with a conventional polyhydroxyether resin comprising bisphenol A. 2,2-bis (4-hydroxyphenyl) having the formula (2) as an R group for improving mechanical properties, thermal properties, solubility in organic solvents, etc. while having a low surface tension, or for economic reasons. In addition to hexafluoropropane (hereinafter referred to as bisphenol AF), the formula (3)
Any of the bisphenols in the group may be used. Inexpensive bisphenol A or 2,2-bis (4-hydroxy-3,5-dimethylphenyl) propane, tetrabromobisphenol A, 4,4 -Biphenol, 1,1-bis (4-
Any of hydroxyphenyl) cyclohexane, bis (4-hydroxyphenyl) sulfone, and bis (4-hydroxy-3,5-dimethylphenyl) sulfone is preferably used.

Further, these polyhydroxyether resins have the specificity that the contact angle to plasma or aqueous protein solution is larger than that of water. Here, a large contact angle indicates that the surface tension of the material is low. Furthermore, the surface tension is lowered and the contact angle with water is 90
゜ In order to achieve the above, at least 20 mol% of the component of the formula (2)
It is necessary to introduce above.

It is desirable that the solvent used for synthesizing the polyhydroxyether resin having a high reduced viscosity dissolves the starting material and the resulting polymer and has a high polarity to promote the nucleophilic reaction of the phenolic hydroxyl group. Examples of such a solvent include aprotic polar solvents such as dimethyl sulfoxide (DMSO), DMAc, N, N-dimethylformamide (DMF), N-methyl-2-pyrrolidone (NMP), sulfolane, dioxane, THF and the like. 2 out of
And a mixed solvent selected from at least one. Of which D
MSO and DMAc are preferred as solvents that are inexpensive, have a high boiling point, are water-soluble, can stir the reaction solution uniformly, and are not decomposed by a base. More preferably DMSO and DMA
c) is a mixed solvent of c and promotes a nucleophilic reaction more than using DMAc alone, thereby obtaining a polyhydroxyether resin having a high viscosity. Further, since the viscosity of the reaction solution of this mixed solvent is lower than that of using DMSO alone, it is easy to stir uniformly.

Here, the term "uniform stirring" means a state in which there is no variation in the reaction in the vessel, stagnation of the solution, solidification due to adhesion of the polymer, and gelation due to partial overheating.

The polymerization reaction includes adding a predetermined amount of a bisphenol, an epihalohydrin and an aqueous solution of NaOH, and stirring with heating. Among epihalohydrins, inexpensive epichlorohydrin (EPC) is preferable.

At this time, in order to obtain a polymer having a reduced viscosity of 0.6 or more, the molar ratio between bisphenols and epichlorohydrin is preferably from 0.95 to 1.05, more preferably from 0.98 to 1.08. 1.02, more preferably 1.0
0.

The polymerization proceeds if the amount of sodium hydroxide is at least equimolar to the amount of bisphenol, but more preferably the ratio of sodium hydroxide to bisphenol is preferably 1.02 to 1.10. Preferably 1.0
4 to 1.08. If the molar ratio of NaOH to bisphenol AF is less than this, a polyhydroxyether resin having a high reduced viscosity cannot be obtained, and if it is more than that, a side reaction occurs to cause crosslinking and conversely, the reduced viscosity decreases.

The reaction temperature can be arbitrarily set as long as it is not higher than the boiling point of the solvent under normal pressure and not lower than room temperature. However, in practice, the solution can be uniformly stirred, and side reactions and coloring are suppressed. In order to complete the polymerization in a short time, the temperature is preferably from 50C to 150C, more preferably from 70C to 130C. If the temperature is lower than this, the progress of the reaction is slow, and if the polymerization proceeds, the reduced viscosity becomes high and stirring becomes difficult. If the temperature is 150 ° C. or higher, side reactions are likely to occur, hindering the progress of the reaction, and coloring the polymer.

Next, the polyhydroxyether film of the present invention will be described.

In order to obtain an asymmetric membrane of the ultrafiltration type,
What is called a wet or dry-wet film formation, in which a polymer is dissolved in an organic solvent, the polymer solution is shaped, and then immersed in a coagulation liquid composed of a non-solvent, is essential. The polyhydroxyether resin represented by the formula (1) is dissolved in a polar organic solvent such as DMSO or DMAc, and an asymmetric film is obtained by a wet or dry-wet film forming method. The asymmetric membrane described here is
Refers to a membrane divided into a dense layer and a porous layer in a direction perpendicular to the membrane surface. An ultrafiltration membrane or a reverse osmosis membrane is often of this type. On the other hand, a symmetric film is a film in which structural anisotropy is not observed in a direction perpendicular to the film surface, and refers to a homogeneous film made of a silicone resin or a porous film made of a polyolefin.

The method for measuring the contact angle according to the present invention is as follows. Paste the dried wet flat membrane on the slide glass,
The sample was placed on a horizontal sample stage of a contact angle measurement device (manufactured by Elma), and about 3 μl of the solution was gently dropped with a syringe on the surface of the membrane in contact with the coagulating solvent, and the values at both ends of the droplet were measured within 30 seconds. Read. This operation was performed five times, and the average value measured was taken as the contact angle.

The ultrafiltration membrane type asymmetric membrane made of this material is capable of suppressing the entry of plasma or water obtained by removing proteins from plasma into the pores. In addition, copolymerization with at least one of various bisphenols having a structure represented by the formula (3) other than bisphenol AF, for improving mechanical properties, thermal properties, solubility in organic solvents, and the like, or for economic reasons. Is also good. Preferably, inexpensive bisphenol A or 2,2 which is supplied stably on an industrial scale
2-bis (4-hydroxy-3,5-dimethylphenyl) propane, tetrabromobisphenol A, 4,4-biphenol, 1,1-bis (4-hydroxyphenyl) cyclohexane,
Bis (4-hydroxyphenyl) sulfone, at least of bis (4-hydroxy-3,5-dimethylphenyl) sulfone
Selected from one or more.

At this time, it is essential that bisphenol AF be contained in an amount of at least 20 mol%, and if it is contained, the contact angle with water is at least 90 ° and the contact angle with plasma is larger than that of water, so that plasma leakage is suppressed. Is possible.

As a method for producing an asymmetric film from the material of the present invention, any method can be used as long as it is a wet film forming method such as an evaporation method and an immersion method. The polymer solution used for film formation is composed of a polyhydroxyether resin, a solvent and a third
When the additives as components are stirred and uniformly dissolved, filtration and defoaming operations are performed. At this time, as a solvent, dimethylsulfoxide, N,
N-dimethylacetamide, N-methyl-2-pyrrolidone, N, N
-Dimethylformamide, THF, acetone, sulfolane or a mixed solvent of one or more thereof is preferred.

The compound used as the third component is selected from an arbitrary amount of water, salt, low molecular weight organic compound or high molecular weight compound, preferably NaCl, LiCl, CaC
_{l 2, MgCl 2, Mg (} ClO 4) 2, LiClO 4, methanol, ethanol, propanol, ethylene glycol, diethylene glycol, propylene glycol, glycerine, urea,
Polypropylene glycol, polyethylene glycol,
Polyvinylpyrrolidone, polyacrylic acid, polyacrylamide or a mixture of one or more thereof, more preferably propylene glycol, which is easy to wash, inexpensive, low toxic and water-soluble.

Although the amount of the additive is optional, it is preferably 5 wt% to 50 wt% in view of spinnability, gas permeability and economy.
Is preferred. Below this, it is difficult to control the membrane structure,
On the other hand, if it is more than this, the polymer precipitates and it is difficult to form a film.

Next, the film forming method of the present invention will be briefly described.

As shown in FIG. 1, the wet flat film is prepared by dropping a film-forming solution on a glass plate, casting it with a glass rod, and immediately immersing it in a coagulating solvent to coagulate it. When coagulation was completed, the membrane was sufficiently washed and dried to obtain a membrane.

The hollow fiber membrane is simultaneously extruded from a double-tube nozzle using a device shown in FIG. 2 to extrude a polymer solution and an internal solution, coagulate in a coagulating solvent, wind up with a winding device, wash and dry, and remove the hollow fiber membrane. Obtained.

Further, it is preferable that the membrane structure is an asymmetric membrane having a dense layer, the pores can be made smaller than that of the polyolefin porous membrane, and it is considered that durability of plasma leak and sufficient gas permeability can be obtained. Can be In order to confirm the structure of the film, a sample was prepared by a freeze-drying method, and after cross-plating platinum, the cross section and surface of the film were observed with a scanning electron microscope JSM840 (manufactured by JEOL Ltd.).

Gas permeability sufficient for an artificial lung membrane may be practically 60 ml / min · m ² · mmHg or more. The gas permeation performance described here was measured by the following method. The wet-type flat membrane is obtained by cutting the dried membrane with a circular punching blade and attaching it to an ultrafiltration membrane permeation performance measuring device (ADVANTEC, UHP-43) as shown in FIG. The gas permeation performance was determined from the permeation amount. The hollow fiber membrane is
The apparatus was attached to the apparatus shown in FIG. 4, and the gas permeation performance was determined from the gas flow rate and the gas flow rate at that time.

[0057]

The present invention will be described more specifically with reference to the following examples. Note that the present invention is not limited to these examples.

(Method of synthesizing polyhydroxyether resin)

(1) In a 100 ml three-necked flask equipped with a motor and a Teflon stirring blade, 50 mm of bisphenol was added.
ol, epichlorohydrin (50 mmol) and a predetermined amount of a solvent were added, and the mixture was stirred under a nitrogen stream and uniformly dissolved. Next, the calculated amount of NaOH solution was accurately dropped with a syringe, and
The mixture was transferred to an oil bath at 0 ° C., and stirring was continued for 20 hours.

(2) Stop heating, and add a predetermined amount of solvent and 1N
An aqueous solution of HCl was added to neutralize the remaining NaOH. Upon cooling to room temperature, a clear, low-viscosity supernatant and an opaque, high-viscosity lower layer were separated. The supernatant was removed by decantation, a solvent was further added, and the mixture was heated and dissolved in a water bath.

(3) The solution was placed in a stainless steel pressure filter (ADVANTEC KST-47) equipped with a glass fiber filter paper (ADVANTEC GB 100R, 100 μm) while hot, and 2 kgf / cm 2 with nitrogen.
^The mixture was filtered under pressure to remove NaCl. When the filtrate was dropped directly into water, a white polymer was immediately precipitated.

(4) The polymer precipitated in a 1 L beaker and 1 L of RO water were added, and the mixture was stirred in a water bath at 80 ° C. for 1 hour. Water was replaced and the process was repeated three times, followed by suction filtration to recover the polymer. After air drying overnight, and then vacuum drying at 80 ° C. overnight, a white polymer was obtained.

(5) The polymer was measured for reduced viscosity, glass transition temperature (Tg), tensile strength at break of molded product, and contact angle by DSC. The degree of polymerization (n) of a polymer having a small reduced viscosity can be determined from the 1H NMR spectrum. In this case, the degree of polymerization (n) was calculated from the integrated intensity ratio of the phenyl group of the main chain and the peak of the phenyl group at the terminal in one polymer molecule.

(6) The polymer having a reduced viscosity of 0.7 (dl / g) or more could not be quantified because the terminal peak was too small.

(Example 1) In a three-necked flask, 16.81 g (50 mmol) of bisphenol AF and 17.3 DMSO were added.
5 g, DMAc 17.35 g, epichlorohydrin4.
63 g was added and dissolved. When a NaOH solution of NaOH / AF = 1.06 was added dropwise, the solution changed from clear yellow to pink. Hereafter, neutralization by HCl, Na by filtration
Removal of Cl, reprecipitation operation, washing and drying were performed to obtain a white fibrous polymer. Its reduced viscosity is 0.6 (dl / g) and its glass transition temperature (Tg) measured by DSC method.
Was 124 ° C. The molded product of this polymer had a tensile strength at break of 450 kg / cm ² . 1H of this polymer
The degree of polymerization determined by NMR was 40. The contact angle of water measured after forming and drying the membrane by the wet method was 100 °, and the contact angle with bovine plasma was 105 °.

Example 2 A white fibrous polymer was obtained in the same manner as in Example 1 except that a NaOH solution that satisfies NaOH / AF = 1.07 was added. Its reduced viscosity is 0.7 (d
l / g).

Example 3 A white fibrous polymer was obtained in the same manner as in Example 1 except that the solvent was 34.7 g of DMSO. Its reduced viscosity was 0.9 (dl / g).

Example 4 Bisphenol AF 10.0
9 g (30 mmol), 4.57 g (20 mmol) of bisphenol A
l) The reduced viscosity of the polymer obtained by polymerization in the same manner as in Example 1 except that NaOH / (AF + A) = 1.04 was 0.7 (dl / g), and the tensile strength at break of the polymer molded product Was 600 kg / cm ² . The contact angle with water was 96 °, and the contact angle with bovine plasma was 100 °.

Example 5 Bisphenol AF 3.36
g (10 mmol), 9.13 g of bisphenol A (40 mmol
l), the reduced viscosity of the polymer obtained by polymerization in the same manner as in Example 1 except that NaOH / (AF + A) = 1.04 was 0.9 (dl / g), and the tensile strength at break of the molded product of the polymer Was 600 kg / cm ² . The contact angle of water measured after drying a membrane prepared from this polymer and dried was 91 °, and the contact angle with bovine plasma was 96 °.

Comparative Example 1 According to the method described in US Pat. No. 3,277,051, the solvent was DMSO 17.35 g NaOH / AF =
Example 1 except for adding a NaOH solution to give 1.04
In the same manner as in the above, a white fibrous polymer was obtained. Its reduced viscosity was 0.5 (dl / g).

(Comparative Example 2) A white powdery polymer was obtained in the same manner as in Example 1 except that a NaOH solution satisfying NaOH / AF = 1.04 was added. Its reduced viscosity is 0.3
(dl / g). This polymer was dissolved in THF and prepared by a dry method, but the film was brittle and no film was obtained. The polymerization degree of this polymer was 30.

Comparative Example 3 A white powdery polymer was obtained in the same manner as in Example 1 except that the reaction time was 3 hours.
Its reduced viscosity was 0.2 (dl / g). This polymer was brittle and no film was obtained. The degree of polymerization of this polymer is 2
It was 0.

(Comparative Example 4) 11.4 g of bisphenol A
(50 mmol) using NaOH / bisphenol A =
A white phenoxy resin was obtained in the same manner as in Example 1 except for adding a 1.04 NaOH solution. Its reduced viscosity was 1.1 (dl / g) and Tg was 100 ° C. The contact angle of water to a film made from this polymer is 80 °,
The contact angle with plasma was 90 °.

Comparative Example 5 A white fibrous material was prepared in the same manner as in Example 1 except that bisphenol A was used and a NaOH solution in which NaOH / bisphenol A = 1.04 was added according to the example described in US Pat. No. 3,277,051. A phenoxy resin was obtained. Its reduced viscosity was 1.2 (dl / g).

(Comparative Example 6) According to the example described in US Pat. No. 3,277,051, bisphenol AF was used and the solvent amount was changed to DMSO.
17.35 g, NaOH / bisphenol AF = 1.0
Polymerization was carried out in the same manner as in Example 1 except that the NaOH solution to be No. 6 was added.

The results of Examples 1 to 5 and Comparative Examples 1 to 6

[Table 1] Shown in

[Table 1]

Example 6 10 g of the polyhydroxyether resin of the formula (5) having a reduced viscosity of 0.7 (dl / g) was added to 50
ml sample bottle with Teflon stirrer, 12 g of propylene glycol, 9 g of DMSO and 9 g of DMAc.
g was added, stirred, dissolved and defoamed to obtain a film forming solution. The solution temperature was maintained at 30 ° C, cast on a glass plate, coagulated as it was in 30 ° C water, washed sufficiently with water, and dried to obtain a wet flat membrane. A portion was freeze-dried while wet, and SEM observation was performed. The film was an asymmetric film, a dense layer was formed, and macrovoids were slightly present (FIG. 5). The surface on the side where the membrane was in contact with the non-solvent was smooth (FIG. 6). When the oxygen permeability was measured, it was 1380 ml / min · m ² · mmHg. The contact angle for this film was 100 ° for water and 110 ° for bovine plasma.

[0078]

Embedded image

Example 7 10 g of a polyhydroxyether resin of the formula (5) having a reduced viscosity of 0.7 (dl / g), 14 g of propylene glycol, 8 g of DMSO and DMAc
A wet flat film was produced in the same manner as in Example 1 except that the amount was 8 g. The membrane was an asymmetric membrane and no macrovoids were observed (FIG. 7), but very small pores were observed on the surface (FIG. 8). Oxygen permeability of this film is 1680ml / min · m ² ·
mmHg. The contact angle for this film is 100
゜, bovine plasma was 110 ゜.

Example 8 10 g of a polyhydroxyether resin of the formula (6) having a reduced viscosity of 0.8 (dl / g), 10 g of propylene glycol, 10 g of DMSO and DMA
A wet flat film was produced in the same manner as in Example 1 except that the amount was c10 g. The membrane was an asymmetric membrane (FIG. 9) and the membrane surface was smooth (FIG. 10). The oxygen permeability of this membrane is 1500
It was ml / min · m ² · mmHg. The contact angle for this membrane was 95 ° for water and 100 ° for bovine plasma.

[0081]

Embedded image

Example 9 10 g of a polyhydroxyether resin of the formula (7) having a reduced viscosity of 0.9 (dl / g), 10 g of propylene glycol, 10 g of DMSO and DMA
A wet flat membrane was produced in the same manner as in Example 1 except that the wet flat membrane was prepared using 10 g of c. The membrane is an asymmetric membrane (FIG. 11),
The film surface was smooth (FIG. 12). The oxygen permeability of this membrane was 100 ml / min · m ² · mmHg. The contact angle for this membrane was 91 ° for water and 97 ° for bovine plasma.

[0083]

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Example 10 100 g of the polyhydroxyether resin of the formula (5) having a reduced viscosity of 0.9 (dl / g) was placed in a 500 ml separable flask, and 120 g of propylene glycol, 90 g of DMSO and 90 g of DMAc were placed.
And stir. After dissolution, defoaming was performed to obtain a film forming solution. The solution temperature was raised to 40 ° C. and extruded from the double spinneret. At this time, water was also supplied as an internal coagulating liquid. The solution discharged from the spinneret was immediately placed in water (coagulation tank) at 10 ° C. to coagulate the spinning solution. Subsequently, the hollow fiber membrane fibers were sufficiently washed with water, and then dried at 50 ° C. for 24 hours. This hollow fiber membrane fiber had an inner diameter of 200 μm and a thickness of 50 μm. The membrane was an asymmetric membrane and the skin layers were smooth on the inner and outer surfaces.
(FIGS. 13, 14, and 15). The oxygen permeability of this membrane was 300 ml / min · m ² · mmHg.

Example 11 100 g of a polyhydroxyether resin of the formula (5) having a reduced viscosity of 0.9 (dl / g)
A solution of 140 g of propylene glycol, 80 g of DMSO and 80 g of DMAc was prepared, and a hollow fiber membrane fiber was obtained in the same manner as in Example 3 except that the solution temperature was 50 ° C and the coagulation bath temperature was 30 ° C. This film has an inner diameter of 200 μm and a thickness of 50 μm.
Met. The film was an asymmetric film, and the skin layer was on the inner surface and the outer surface, and both surfaces were smooth (FIGS. 16, 17, and 1).
8). The oxygen permeation performance of this membrane is 1600 ml / min · m ² · mmHg
Met.

Example 12 100 g of polyhydroxyether resin of the formula (5) having a reduced viscosity of 0.9 (dl / g), 160 g of propylene glycol, 70 g of DMSO and DM
A solution of 70 g of Ac was prepared, and a hollow fiber membrane fiber was obtained in the same manner as in Example 3 except that the solution temperature was 50 ° C and the coagulation bath temperature was 30 ° C. This film had an inner diameter of 200 μm and a thickness of 50 μm. The film was an asymmetric film, and the skin layer was on the inner surface and the outer surface, and small holes were observed on the outer surface side at a magnification of 10,000 times with a scanning electron microscope (FIGS. 19, 20, and 21). The oxygen permeability of this membrane was 2000 ml / min · m ² · mmHg.

Example 13 100 g of a polyhydroxyether resin of the formula (6) having a reduced viscosity of 0.8 (dl / g), 160 g of propylene glycol, 70 g of DMSO and DM
A solution of 70 g of Ac was prepared, and a hollow fiber membrane fiber was obtained in the same manner as in Example 3 except that the solution temperature was 50 ° C and the coagulation bath temperature was 30 ° C. This film had an inner diameter of 200 μm and a thickness of 50 μm. The membrane was an asymmetric membrane, the skin layer was on the inner and outer surfaces, and the outer surface was smooth (FIGS. 22, 23, 2).
4). The oxygen permeability of this membrane was 300 ml / min · m ² · mmHg.

Comparative Example 7 50 g of a 10 g polyhydroxyether resin of the formula (5) having a reduced viscosity of 0.3 (dl / g) was used.
Put into a sample bottle with a magnetic stirrer chip, add 12 g of propylene glycol, 9 g of DMSO and 9 g of DMAc, and stir. After dissolving, defoaming, maintaining the solution temperature at 30 ° C., casting on a glass plate,
Although immersed in water at 0 ° C., it did not solidify and a film was not obtained.

Comparative Example 8 50 ml of 10 g of the polyhydroxyether resin of the formula (5) having a reduced viscosity of 0.5 (dl / g)
Put into a sample bottle with a magnetic stirrer chip, add 12 g of propylene glycol, 9 g of DMSO and 9 g of DMAc, and stir. After dissolving, defoam, maintain the solution temperature at 30 ° C, cast on a glass plate and
Although the film was obtained by immersing it in water at ℃, it was brittle and it was difficult to maintain its shape.

(Comparative Example 9) A solution was prepared from 11 g of polysulfone P-3500 manufactured by Amoco, 7 g of propylene glycol and 32 g of N-methylpyrrolidone according to JP-B-63-25784, and a flat membrane was prepared in the same manner as in Example 1. did. This membrane was an asymmetric membrane (FIGS. 25 and 26) and had an oxygen permeability of 500 ml / min · m ² · mmHg. The contact angle for this film was 88 ° for water and 98 ° for bovine plasma.

Comparative Example 10 10 g of a polyhydroxyether resin of the formula (8) having a reduced viscosity of 0.9 (dl / g), 10 g of propylene glycol, 10 g of DMSO and DM
A wet flat film was produced in the same manner as in Example 1 except that the amount of Ac was 10 g. This membrane is an asymmetric membrane (FIGS. 27 and 28)
The oxygen permeability was 30 ml / min · m ² · mmHg. The contact angle for this membrane was 80 ° for water and 89 ° for bovine plasma.

[0092]

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Comparative Example 11 A commercially available polyolefin artificial lung membrane had an oxygen permeability of 1400 ml / min · m ² · mmHg.
Pores were recognized on the membrane surface, and the cross section was a porous symmetric membrane having the same structure (FIGS. 29 and 30).

[0094]

The polyhydroxyether resin and the polyhydroxyether film of the present invention are characterized by having a reduced viscosity of 0.6 or more, a high degree of polymerization, and containing no insoluble and infusible components. The resin of the present invention is also superior in mechanical strength as compared with the conventionally known polyhydroxyether resin having a degree of polymerization of 20 or less, and has a larger contact angle with plasma or aqueous protein solution than with water, Moreover, it has the specificity that the contact angle with water is 90 ° or more. Furthermore, the glass transition temperature Tg is higher than that of the conventional polyhydroxyether resin comprising bisphenol A.
And its surface tension is low.

The polyhydroxyether film of the present invention can be obtained by polycondensation of 2,2-bis (4-hydroxyphenyl) hexafluoropropane or other bisphenols with a halogenated epoxy (epichlorohydrin or the like). Is dissolved in an organic solvent such as DMSO or DMAc and obtained by a wet method.

Further, this polyhydroxyether membrane is an asymmetric membrane, and 1) its ability to prevent the invasion of plasma is larger than that of the PP porous membrane due to its small pore diameter. 3) Since the contact angle with water is 90 ° or more, it also suppresses the permeation of water as plasma filtrate. 4) It has excellent gas permeability as an artificial lung membrane. I have.

[Brief description of the drawings]

FIG. 1 is a view showing a method for producing a wet flat film.

FIG. 2 is a view schematically showing a spinning apparatus.

FIG. 3 is a diagram showing a method for measuring gas permeation performance of a wet flat membrane.

FIG. 4 is a view showing a method for measuring gas permeation performance of a hollow fiber membrane.

FIG. 5 is an SEM photograph of a cross section of a flat film.

FIG. 6 is an SEM photograph of a flat film surface.

FIG. 7 is an SEM photograph of a cross section of a flat film.

FIG. 8 is an SEM photograph of a flat film surface.

FIG. 9 is an SEM photograph of a cross section of a flat film.

FIG. 10 is an SEM photograph of a flat film surface.

FIG. 11 is an SEM photograph of a cross section of a flat film.

FIG. 12 is an SEM photograph of a flat film surface.

FIG. 13 is an SEM photograph of a cross section of a hollow fiber membrane.

FIG. 14 is an SEM photograph of the outer surface of the hollow fiber membrane.

FIG. 15 is an SEM photograph of the outer surface of the hollow fiber membrane.

FIG. 16 is an SEM photograph of a cross section of a hollow fiber membrane.

FIG. 17 is an SEM photograph of the outer surface of the hollow fiber membrane.

FIG. 18 is an SEM photograph of the outer surface of the hollow fiber membrane.

FIG. 19 is an SEM photograph of a cross section of a hollow fiber membrane.

FIG. 20 is an SEM photograph of the outer surface of the hollow fiber membrane.

FIG. 21 is an SEM photograph of the outer surface of the hollow fiber membrane.

FIG. 22 is an SEM photograph of a cross section of a hollow fiber membrane.

FIG. 23 is an SEM photograph of the outer surface of the hollow fiber membrane.

FIG. 24 is an SEM photograph of the outer surface of the hollow fiber membrane.

FIG. 25 is an SEM photograph of a cross section of a flat film.

FIG. 26 is an SEM photograph of a flat film surface.

FIG. 27 is an SEM photograph of a cross section of a flat film.

FIG. 28 is an SEM photograph of a flat film surface.

FIG. 29 is an SEM photograph of a cross section of a polyolefin hollow fiber membrane.

FIG. 30 is an SEM photograph of the surface of a polyolefin hollow fiber membrane.

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Claims (10)

[Claims] 1. A polyhydroxyether resin not containing an insoluble and infusible gel represented by the formula (1), wherein the polyhydroxyether resin has the formula (1) In the polyhydroxyether resin, the R group represented by the formula (2) is 100 mol% to 20 mol%, and the formula (2) The remaining R groups are any of the group of R groups represented by Formula (3), and are represented by Formula (3): N, N- is added to 0.5 g of the polyhydroxyether resin.
A polyhydroxyether resin characterized by having a reduced viscosity at 25 ° C of 0.6 (dl / g) or more at 25 ° C of a solution obtained by adding dimethylacetamide and dissolving to 100 ml. 2. The polyhydroxyether according to claim 1, wherein the remaining R group of the polyhydroxyether resin is any one of a group of R groups represented by formula (4). resin. Formula (4) 3. The polyhydroxyether resin according to claim 1, wherein the contact angle with plasma or aqueous solution of protein is larger than the contact angle with water, and the contact angle with water is 90 ° or more. 4. An aprotic polar solvent comprising reacting at least one bisphenol having one of the structures represented by the formula (5) with epihalohydrin. A method for synthesizing a polyhydroxyether resin. Formula (5) 5. The aprotic polar solvent comprises at least one kind of bisphenol having any structure of the group represented by the formula (5), and a molar ratio of the bisphenol to the bisphenol is 0. 95 to 1.05 epihalohydrin and an aqueous solution of sodium hydroxide in an equimolar amount or more with respect to the bisphenol, and the mixture is uniformly stirred at a reaction temperature not lower than room temperature and not higher than the boiling point of the aprotic polar solvent. The method for synthesizing a polyhydroxyether resin according to claim 4. 6. The aprotic polar solvent is dimethyl sulfoxide, N, N-dimethylacetamide, tetrahydrofuran, dioxane, N-methylpyrrolidone, N, N-dimethylformamide, sulfolane or a mixed solvent thereof. The method for synthesizing a polyhydroxyether resin according to claim 4 or 5, wherein 7. A polyhydroxyether film represented by the formula (1), wherein the polyhydroxyether film is represented by the formula (1): In the polyhydroxyether film, the R group represented by the formula (2) is 100 mol% to 20 mol%, and the formula (2) The remaining R groups are any of the group of R groups represented by Formula (3), and are represented by Formula (3): N, N-dimethylacetamide is added to 0.5 g of the polyhydroxyether film and dissolved to make 100 ml, and the reduced viscosity at 25 ° C. is 0.6 (dl / g) or more. Hydroxy ether membrane. 8. The polyhydroxyether according to claim 1, wherein the remaining R groups of the polyhydroxyether film are any one of a group of R groups represented by the formula (4). film. Formula (4) 9. A polyhydroxyether resin not containing an insoluble and infusible gel represented by the formula (1), dimethyl sulfoxide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone, N, N-dimethyl Formamide, THF, acetone,
Using a solution prepared by adding and dissolving any one of sulfolane or a mixed solvent thereof and water, a salt, a low molecular weight compound or a high molecular weight compound as a third component,
A method for producing a polyhydroxyether film, which is produced by a dry-wet method or a wet film-forming method. Formula (1) However, the R group represented by the formula (2) is 100 mol% to 20 mol.
%, And the formula (2) The remaining R groups are any of the groups of R groups represented by formula (3): 10. The method according to claim 10, wherein the salt, low molecular weight compound or high molecular weight compound is NaCl, LiCl, CaCl ₂ , MgCl ₂ , Mg (ClO ₄ ) ₂ , L
iClO ₄ , methanol, ethanol, propanol, ethylene glycol, diethylene glycol, propylene glycol, glycerin, urea, polypropylene glycol, polyethylene glycol, polyvinylpyrrolidone,
The polyhydroxyether membrane according to claim 9, wherein the polyhydroxyether membrane is any one of polyacrylic acid and polyacrylamide or a mixture thereof, and the third component is 5 wt% to 50 wt% in the film forming solution. Manufacturing method.