JPH10109023A - Hollow fiber type selective separation membrane - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a hollow fiber type selective separation membrane using a polysulfone polymer, excellent in chemical resistance and membrane strength and having aging stabilities of the rate of ultrafiltration and the separating performance of solute. SOLUTION: This hollow fiber type selective separation membrane has a 10-35μm membrane thickness, a 100-300μm inside diameter and 50-85% porosity and contains a polysulfone polymer. The reduced viscosity of the polymer in 1wt.% soln. of dimethyformamide is 0.55-0.85. A dialysis and/or filtration module using this selective separation membrane can stably remove a large amt. of water over a long period of time, can efficiently remove a solute by dialysis and/or filtration even at the time of removing a large amt. of water and is suitable for ultrafiltration, reverse osmosis, gas separation, blood purification, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a hollow fiber type selective separation membrane using a polysulfone polymer. More specifically, the present invention relates to a hollow fiber type selective separation membrane using a polysulfone-based polymer which is less clogged in dialysis and filtration of various fluids and has stable filtration performance with time.

[0002]

2. Description of the Related Art Many types of membranes have been used for the purpose of dialysis and filtration of various fluids such as various solutions and gases. Most of these membranes are hollow fiber type selective separation membranes, but since hollow fiber type selective separation membranes are expensive, these membranes are often regenerated and reused in recent years. Therefore, a hollow fiber type selective separation membrane having more excellent chemical resistance and membrane strength has been developed.

At present, materials having excellent chemical resistance and membrane strength include polysulfone-based and polyolefin-based polymers. In particular, hollow-fiber-type selective separation membranes using polysulfone-based polymers are available from ultrafiltration, Widely used in fields such as reverse osmosis, gas separation, and blood purification membranes.

However, such a hollow fiber type selective separation membrane using a polysulfone-based polymer is liable to be contaminated because the polysulfone-based polymer is a hydrophobic polymer, so that the selective separation of the membrane is deteriorated. It has the disadvantage that it is easy to occur. In particular, when a polysulfone-based selective separation membrane is used for blood purification or the like, since blood cells and proteins are contained in blood, clogging of the membrane occurs, protein adsorption or a protein gel layer is formed on the membrane surface. Thus, a polarized protein layer at the blood lateral membrane, a so-called secondary layer, is formed. As described above, when used as a blood purification membrane, there is a problem that clogging occurs and solute removal performance is reduced, and a secondary layer is formed, so that a filtration flow rate is reduced.

Various proposals have been made to solve the above problems. For example, in Japanese Patent Application Laid-Open No. 1-94902,
It describes a polysulfone asymmetric hollow fiber membrane which has excellent dialysis performance and has little deterioration over time in filtration rate during long-term use. However, the membrane adsorbs to the membrane rather than being filtered, so that β2-microglobulin (hereinafter, β2-MG) in the blood is absorbed.
Therefore, the amount of β2-MG that can be removed by the membrane has a limit value called the amount of adsorption saturation. Also, β2-M
Even if G can be removed, several thousand molecular weights other than β2-MG
The removal performance of tens of thousands of harmful substances (uremic substances) is unknown, and it cannot be said that such harmful substances are sufficiently removed.

Further, Japanese Patent Publication No. 5-54337 discloses an asymmetric hollow fiber membrane for blood treatment having excellent solute permeability. Although the membrane has excellent dialysis removal performance and clearance even at a high filtration flow rate,
It has been shown that the clearance of even low molecular substances such as urea is lower at the end of dialysis than at the start of dialysis, and it is considered that harmful substances of low molecular proteins such as β2-MG can be removed stably. Absent.

As described above, the chemical resistance and the membrane strength are excellent, and the filtration rate and solute removal performance are stable over time, and uremic diseases such as β2-MG which are particularly problematic in the field of hemodiafiltration. At present, a hollow fiber type selective separation membrane capable of effectively removing substances has not yet been obtained.

[0008]

DISCLOSURE OF THE INVENTION The present inventors have conducted intensive studies on the membrane structure of a hollow fiber type selective separation membrane using a polysulfone polymer in order to solve the above-mentioned problems.
In particular, by forming the membrane with a polysulfone-based polymer in a high molecular weight region, clogging on the active surface of the membrane and generation of a so-called polarized secondary layer can be suppressed, and as a result, performance degradation due to membrane fouling can be suppressed. I found that it was possible.

In view of the above, the present inventors have found that when a polysulfone-based or polyethersulfone-based polymer in the polymer region is used, the coagulation property of the membrane during spinning is appropriately improved, that is, when the membrane is coagulated. It is presumed that the nuclei are easily generated and the generated nuclei are easily grown, so that the film surface of the formed film has less unevenness and a film structure with more uniform pore shape and size can be obtained. However, no support is available at this time.

Although the surface structure of the film is observed with an electron microscope, the limit is 5000 times in order to prevent the polymer on the film surface from being melted by the heat generated by the electron microscope. On the other hand, in order to perform a more detailed analysis of the film surface structure, it is considered necessary to observe at least tens of thousands of times with an electron microscope, and the observation of the film structure with the above-mentioned electron microscope is not sufficient. Therefore, in the present application, the smoothness of the membrane surface is expressed by the solute permeability during blood filtration and the temporal stability of the ultrafiltration rate.

In addition to the above, when the inside of the membrane has a substantially uniform structure, it is possible to prevent contamination of foreign substances (eg, endotoxin) from the dialysate side by back-filtration at the module outlet, thereby reducing the hydrophilic polymer. It is considered that such a case provides an advantage that the hydrophilic polymer is confined in the membrane structure and firmly fixed.

The present invention has been completed as a result of further studies based on the above findings.

[0013]

That is, the present invention provides:
A hollow fiber type selective separation membrane containing a polysulfone polymer having a film thickness of 10 to 35 μm, an inner diameter of 100 to 300 μm, and a porosity of 50 to 85%, wherein the polysulfone polymer is in a 1% by weight solution of dimethylformamide. Is a hollow fiber type selective separation membrane having a reduced viscosity of 0.55 to 0.85.

In a preferred embodiment, the hollow fiber type selective separation membrane of the present invention contains a hydrophilic polymer.

[0015] In a preferred embodiment, the hydrophilic polymer is polyvinylpyrrolidone.

In a preferred embodiment, the hollow fiber type selective separation membrane of the present invention contains a membrane structure retention agent.

[0017] In a preferred embodiment, the membrane structure-retaining agent is glycerin.

In a preferred embodiment, there are no holes and irregularities that are clearly observed when the film surface is observed at a magnification of 5000 times, and substantially when the film cross section is observed at a magnification of 200 times. Is uniform.

In a preferred embodiment, bovine blood having a hematocrit of 25 to 30% and a protein concentration of 6 to 7 g / dl is passed through a module filled with the hollow fiber type selective separation membrane of the present invention at a flow rate of 200 ml / min. 10ml / m
The ratio of the sieving coefficient of β2-microglobulin when blood filtration is performed at a filtration flow rate of 50 ml / min to the sieving coefficient of β2-microglobulin when blood filtration is performed in 60% or more.

In a preferred embodiment, bovine blood having a hematocrit of 25 to 30% and a protein concentration of 6 to 7 g / dl is passed through a module filled with the hollow fiber type selective separation membrane of the present invention at a flow rate of 200 ml / min. 50ml / m
The ratio of the ultrafiltration rate at 5 hours after the start of filtration to the ultrafiltration rate at 10 minutes after the start of filtration when performing blood filtration in is 70% or more.

Hereinafter, the present invention will be described in detail.

The thickness of the hollow fiber membrane type selective separation membrane of the present invention is 1
0 to 35 μm. When the film thickness is less than 10 μm, the strength of the film is reduced, and it is difficult to keep the film thickness constant, so that productivity is significantly reduced. On the other hand, if the film thickness exceeds 35 μm, the phase separation state at the time of film formation is not uniform, so that the smoothness of the inner surface of the film cannot be maintained. It causes the resistance to rise. In particular, when a large amount of water is removed, the degree of decrease in the ultrafiltration rate over time becomes large, and it becomes difficult to maintain high dialysis and filtration performance. Preferred film thickness is 15 to 35 μm
m.

The porosity of the hollow fiber type selective separation membrane of the present invention is 5
0% to 85%. If the porosity is less than 50%, sufficient solute removal performance cannot be obtained, making the composition unsuitable for blood purification applications. If the porosity exceeds 85%, the strength of the hollow fiber type selective separation membrane is reduced. A decrease causes a decrease in productivity. The porosity is determined by measuring the porosity of the membrane after washing with water for 1 to 2 hours, followed by water adhering to the membrane surface (water adhering to the outer surface and water remaining in the core).
The weight is measured (weight A), and after absolute drying at 105 ° C., the weight is measured (weight B) and calculated by the following equation. Porosity = (weight A−weight B) / ｛(weight A−weight B) +
(Weight B / ρ)｝ 100% where ρ is the specific gravity of the polymer

The hollow fiber type selective separation membrane of the present invention has an inner diameter of 10
It is 0 μm to 300 μm. When the inner diameter is less than 100 μm, the pressure loss when flowing blood becomes large, which may damage the blood and cause hemolysis, and may cause the blood to coagulate and form a thrombus in the hollow portion. Absent. When the inner diameter exceeds 300 μm, the hollow portion becomes too large, it is difficult to maintain the hollow shape, and the productivity is reduced. In addition, the shear rate on the inner surface of the hollow fiber membrane is reduced, and proteins and the like are easily deposited on the inner surface of the membrane with the filtration.
The preferred inner diameter is between 120 and 250 μm.

The polysulfone polymer constituting the hollow fiber type selective separation membrane of the present invention is not particularly limited.
All polymers having a sulfone group in the molecule can be used. Examples of the polysulfone-based polymer include, for example, polysulfone (chemical formula 1), polyether sulfone (chemical formula 2), polyaryl sulfone, and the like. Among them, polyethersulfone and polysulfone are particularly preferable because the balance between the hydrophilicity and the hydrophobicity of the polymer is good and the adsorption of the protein to the membrane is low.

[0026]

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[0027]

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The polysulfone polymer constituting the hollow fiber type selective separation membrane of the present invention is 1% by weight of dimethylformamide.
The reduced viscosity of the solution is 0.55 to 0.85. When the reduced viscosity of a 1% by weight solution of dimethylformamide is less than 0.55, the obtained hollow fiber membrane has poor surface smoothness and uniformity, and causes clogging and so-called polarization on the membrane surface during dialysis / filtration treatment. A secondary layer is easily formed. Further, since the film strength is weak, the handling property is poor and the productivity is reduced. When the reduced viscosity exceeds 0.85, productivity decreases due to a decrease in solubility of the polysulfone or polyethersulfone polymer and a decrease in filter life due to an increase in back pressure of the line filter of the spinning device. The preferred reduced viscosity is 0.6 to 0.85.

In the present invention, the reduced viscosity η of the polysulfone polymer is determined by measuring the viscosity η1 and η of the solution of the dried polysulfone polymer dissolved in dimethylformamide at 1% by weight and the solvent dimethylformamide.
0 is a value measured by an Ostwald viscometer and calculated by the following equation. η = ((η1−η0) / η0) / c η0: viscosity of solvent η1: viscosity of solution c: concentration of solute (g / dl) The reduced viscosity of the polysulfone polymer constituting the hollow fiber membrane is When the membrane is composed of only a polysulfone-based polymer, it may be measured and determined as described above, but in the present application including the case where the polymer contains other polymers, the reduced viscosity of the polysulfone-based polymer in the hollow fiber membrane is as follows: Ask as follows. First, a hollow fiber membrane is dissolved in dimethylfomamide to prepare a sample solution (reduced viscosity: X). Next, two kinds of polyether sulfones having reduced viscosities of about 0.5 and about 0.8 and having known reduced viscosities are dissolved in dimethylformamide to prepare standard solutions 1 and 2 (reduced viscosities: A and B). Gel filtration is performed using dimethylformamide as a mobile layer using the standard solutions 1 and 2 and the sample solution to determine the respective mobilities (mobilities: a, b, x). The reduced viscosity (X) of the polysulfone-based polymer in the sample solution is determined by the following equation. X = B− (BA) × (b−x) / (ba) where X: reduced viscosity of polysulfone polymer in hollow fiber membrane A: polyether sulfone having reduced viscosity of about 0.5 B: Reduced viscosity of polyethersulfone having a reduced viscosity of about 0.8 x: Mobility of polysulfone-based polymer in hollow fiber membrane a: Mobility of polyethersulfone having a reduced viscosity of about 0.5 b : Mobility of polyether sulfone having a reduced viscosity of about 0.8 In the present invention, X thus obtained is defined as the reduced viscosity of the polysulfone polymer in the hollow fiber membrane.

The hollow fiber type selective separation membrane of the present invention preferably contains a hydrophilic polymer. The type of the hydrophilic polymer is not particularly limited, and examples thereof include polyvinyl pyrrolidone, polyvinyl alcohol, and polyethylene glycol. Above all, polyvinylpyrrolidone has good compatibility with the polysulfone-based polymer, and is particularly preferable for enhancing the hydrophilicity of the membrane. There are several types of these hydrophilic polymers depending on the degree of polymerization, and any type of molecular weight can be used.However, the higher the molecular weight, the more difficult the elution out of the membrane to occur. It is desirable to do.

The hollow fiber type selective separation membrane of the present invention preferably contains a membrane structure retention agent. Polyhydric alcohol is preferable as the membrane structure-retaining agent, and examples thereof include glycerin, ethylene glycol, and propylene glycol.
Among them, glycerin is particularly preferable in terms of safety and cost.

The hollow fiber type selective separation membrane of the present invention has a membrane surface
When observed under an electron microscope at 5000 × magnification, there are no clearly recognized holes and irregularities. That is, the membrane surface of the hollow fiber type selective separation membrane of the present application is substantially smooth,
Because of the smoothness, clogging of the membrane and generation of a so-called secondary layer are suppressed, and the ultrafiltration rate and the solute separation performance are stabilized over time. In addition, the fact that there is no hole clearly observed when observed with an electron microscope at 5000 times means that 50
It means that there is no hole with a diameter of 0.2 mm or more, that is, a hole with a diameter of 400 Å or more on the inner surface in an enlarged photograph of 00 times, and that there is no unevenness clearly observed when observed with a 5000 times electron microscope. This means that there is substantially no unevenness having a size of 1 mm in an enlarged photograph of 5000 times, that is, 0.2 μm or more on the inner surface.

The cross section of the hollow fiber type selective separation membrane of the present invention is as follows:
When observed under an electron microscope at a magnification of 200 times, the structure is substantially uniform. When the inside of the film has a non-uniform structure, the separation by the film is performed only on the film surface.If a partial defect or fluctuation at the time of separation occurs on the film surface, the film Clogging is likely to progress at the center, and particularly when filtering blood containing a large amount of blood cells or proteins, the influence of these components on clogging becomes very large. On the other hand, since a uniform membrane supports filtration in the entire membrane, even when there is a defect as described above in a part of the membrane surface, the entire membrane can cover such a defect and suppress the clogging as described above. . That is, when the membrane has a uniform structure, the entire internal structure of the membrane can support filtration and exhibit stable diafiltration performance. Here, that the inside of the membrane has a substantially uniform structure means that the hollow fiber membrane does not have asymmetry in its radial direction and cross-sectional direction, and is not merely symmetrical in the radial direction,
This means that a homogeneous porous structure is formed substantially in the thickness portion of the film. Therefore, when the hollow fiber type selective separation membrane of the present invention is washed with water, freeze-dried so as to retain the membrane structure, and observed with a microscope, the cross-sectional structure of the membrane is observed as a finger-like structure or a network structure. Means that it is observed as a non-uniform structure.

Further, when the film has a non-uniform structure,
For example, when the membrane is formed of a hydrophobic polymer and a hydrophilic polymer, the hydrophilic polymer in the membrane flows out from the large pores of the membrane, and changes in membrane performance and elutions from the membrane cause many problems. In some cases, when the membrane has a uniform structure, the hydrophilic polymer in the membrane is trapped in the membrane tissue and is firmly fixed, and the above-described problem does not occur. In addition, in the case of a nonuniform membrane having a large pore diameter outside the membrane, there is a risk that foreign substances may contaminate from the dialysate side, but there is an advantage that a uniform membrane does not have such a risk.

In such a uniform membrane, the hollow fiber is filled at a filling rate of 5%.
Bovine blood with an anticoagulant added to a module with a membrane area of 1.5 m ² filled with 5% is flowed inside or outside the hollow fiber membrane at a flow rate of 200 ml / min to perform blood filtration. Ultrafiltration rate (ml / min
mmHg) can be confirmed from the fact that there is substantially no difference between the inner and outer surfaces of the film. In addition, since the hollow fiber type selective separation membrane of the present invention also has a smooth membrane surface on the dialysate side during the blood purification treatment, contamination from the dialysate side can be prevented, and the filtrate can be smoothly transferred to the dialysate.

The module filled with the hollow fiber type selective separation membrane of the present invention has a hematocrit of 25 to 30% and a protein concentration of 6
牛 7 g / dl of bovine blood at a flow rate of 200 ml / min to perform blood filtration, the filtration rate was 50 ml / min for the sieving coefficient of β2-MG (molecular weight: 11,600) when the filtration rate was 10 ml / min. β2-
The ratio of the sieving coefficient of MG is 60% or more. This ratio is 60
%, The removal rate of thousands or tens of thousands of uremic substances having a molecular weight of β2-MG or the like during the large-scale water removal therapy becomes insufficient, and the improvement effect by the large-scale water removal therapy is sufficiently obtained. Because there is no. The preferred ratio is at least 65%.

The effect of the present invention on the protein concentration of bovine blood and the rate of ultrafiltration of hematocrit used in the present invention is large, and in the present invention, the performance evaluation of the membrane summarized by the Working Group of the High Performance Membrane Research Society was conducted. Method, the hematocrit value was 25% to 30% and the protein concentration was 6 to 7 g / dl.
It was determined with reference to the description that the blood was bovine blood at ° C.

The module filled with the hollow fiber type selective separation membrane of the present invention has a hematocrit of 25 to 30% and a protein concentration of 6
When bovine blood of ７7 g / dl is flowed at a flow rate of 200 ml / min to perform blood filtration, the sieving coefficient of β2-MG is preferably 0.5 or more when the filtration rate is 10 ml / min. When the sieving coefficient of β2-MG is less than 0.5, HF
This is because the efficiency of removing uremic substances having a molecular weight of thousands to tens of thousands including β2-MG in HDF treatment is low, and a sufficient therapeutic effect cannot be obtained. More preferably, the sieving coefficient of β2-MG is 0.55 or more.

The module filled with the hollow fiber type selective separation membrane of the present invention has a hematocrit of 25 to 30% and a protein concentration of 6
７7 g / dl of bovine blood at a flow rate of 200 ml / min and a filtration rate of 50 ml / min for blood filtration.
The ratio of the ultrafiltration rate 5 hours after the start of hemofiltration to the ultrafiltration rate 10 minutes after the start of hemofiltration is 70% or more. If the ratio is less than 70%, the filtration efficiency is greatly reduced due to clogging, and the removal performance is reduced.

The hollow fiber type selective separation membrane of the present invention can be produced, for example, as follows, but the present invention is not limited to the following. The spinning dope comprises a polymer or a combination of a plurality of polymers and a solvent or a combination of a plurality of solvents, and a non-solvent or a combination of a plurality of non-solvents. As the composition in the spinning solution,
The weight fraction of the total polymer is suitably from 15 to 35% by weight. If it is less than 15%, the spinning solution has a low viscosity and the spinnability is low, and if it is 35% or more, the phase separation is too fast. The total solvent fraction is preferably 30 to 70% by weight, and the total non-solvent fraction is preferably 5 to 50% by weight. The above spinning stock solution is heated to room temperature to 190 ° C to uniformly dissolve, then degassed and filtered, and then extruded from the outside of the double-tube spinning port, and 50 to 160 ° C from the center.
Is supplied at a constant rate. The extruded spinning solution is allowed to travel in the air at a fixed distance of 1 to 20 mm, and then coagulated in a coagulating liquid at 5 to 60 ° C. to form a membrane structure. After washing with water, it is passed through a 30 to 60% by weight aqueous glycerin solution to maintain the membrane structure,
After impregnating with glycerin, it is dried in a drier and wound up.

Examples of the solvent used above include a so-called aprotic polar solvent, N, N-dimethylformamide,
N, N-dimethylacetamide, γ-butyrolactone,
N-methylpyrrolidone or the like is used alone or in combination.
Examples of the non-solvent include inorganic salts and alcohols, and it is preferable to use glycols such as glycerin, ethylene glycol, triethylene glycol and polyethylene glycol alone or as a mixture. In particular, the non-solvent is important for controlling phase separation, for example, in the presence of glycerin. Preferably, phase separation is suppressed.
As the coagulable liquid, water or a mixed aqueous solution of water and a solvent used in the spinning solution and a non-solvent can be used.

In the present invention, in order to make the pore size on the inner surface of the membrane small and uniform and to obtain a smooth surface state, the membrane is preferably formed by a dry-wet spinning method using gas as a hollow forming agent. Here, the gas to be used includes, for example, nitrogen, helium, air and the like, but it is preferable to use nitrogen from the viewpoint of quality and supply stability. Also,
In order to further improve the smoothness of the surface state as described above, and to further improve the water permeability and separation properties in hemodiafiltration and the like and the retention thereof, the temperature of the gas used as the hollow forming agent is set to be 20 degrees lower than the temperature of the coagulable liquid. It is particularly preferable to raise the temperature by at least 0 ° C. Further, it is preferable that the hollow fiber is spun substantially without drawing, that is, it is wound up with only a force necessary for taking up the hollow fiber without forcibly drawing. This is for suppressing deformation of the holes formed in the film. Here, "substantially non-stretching" means that the film is not stretched by 10% or more in each step of spinning.

The SC and UFR (B) of β2-MG of the hollow fiber type selective separation membrane of the present invention are measured by the following methods. When the hollow fiber type selective separation membrane of the present invention is a hollow fiber membrane,
0000 hollow fiber membranes are placed in a plastic molded product to produce a module. After this module was washed with physiological saline, the above-mentioned bovine blood was placed on the blood side at 200 ml / vol.
Pour in minutes. The pressure at the inlet and outlet on the module blood side or the pressure on the dialysate side is adjusted so as to give a filtration flow rate of 10 or 50 ml / min per 1.5 m ² of membrane area of the module.

1. β2-MG SC At a filtration rate of 10 or 50 ml / min, blood and filtrate at the inlet and outlet of the module at 15 minutes after the start of blood filtration are sampled and subjected to enzyme immunoassay (eg, Glazyme β).
Β by 2-Microglobulin-EIA Test Wako Pure Chemical Industries, Ltd.
Measure the concentration of 2-MG. In this measurement, a suitable amount of human-derived β2-MG is added to bovine blood flowing to the module in the measurement, and the sampled blood is centrifuged, if necessary, for measurement of β2-MG. From these β2-MG concentration values, the SC of β2-MG is determined according to the following equation 1. SC = Cfil / ((CI + Co) / 2) (Equation 1) Cfil: β2-MG concentration of filtrate CI: β2-MG concentration of blood at inlet of module blood side CO: β2-MG of blood at outlet of module blood side concentration

2. UFR (B) retention The pressures at the inlet and outlet on the blood side and the filtrate side of the module at 15 minutes and 5 hours after the start of blood filtration at a filtration rate of 50 ml / min are measured. UFR (B) was calculated from these pressure values according to the following equation 2, and the ratio of UFR (B) at 5 hours to UFR (B) at 15 minutes after the start of hemodialysis (retention rate of UFR (B)) Ask for. UFR (B) = Qf / (A × ((PI + PO) / 2-Pfil)) (Equation 2) Qf: Ultrafiltration speed (ml / hour) A: Surface area of the membrane (m ² ) PI: Module blood side Inlet pressure (mmHg) PO: pressure at module blood side outlet (mmHg) Pfil: pressure at module filtrate side (mmHg)

[0046]

EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

Example 1 20% by weight of a polyether sulfone having a reduced viscosity of 0.62 in a 1% by weight solution of dimethylformamide, 5% by weight of polyvinylpyrrolidone (K-90), and N-methyl-2- as a solvent Pyrrolidone 37.5
% By weight, polyethylene glycol # 200 as non-solvent
Is heated from 110.degree. C. to a solution obtained by dissolving a raw material consisting of 37.5% by weight, extruded from the outside of the double tubular spinneret, and nitrogen heated to 80.degree. After traveling for 7 mm, the mixture was passed through a coagulating liquid at 15 ° C. in which water, N-methyl-2-pyrrolidone, and polyethylene glycol # 200 were mixed in a weight ratio of 70:15:15 to complete coagulation. . After that, it is washed with water and impregnated with 50% by weight of glycerin, and then dried by a drier to have an inner diameter of 201 μm, a thickness of 21 μm, and a porosity of 78
% Of hollow fiber membrane was obtained. When the inner surface and outer surface of the hollow fiber membrane were observed with an electron microscope (hereinafter, SEM), as shown in FIGS. 3 and 4, both the inner surface and the outer surface had pores and irregularities even at a magnification of 5000 times. It was a smooth structure in which no was observed. Further, the hollow fiber membrane was taken along AA shown in FIG.
When a part of the cross section (FIG. 2) cut along the line (the inside of the enclosing line B in FIG. 2) was observed at a magnification of 200 times, a tissue image was observed inside the film as shown in FIG. It was confirmed that the structure was not uniform. 8,400 hollow fiber membranes were housed in a plastic molded product, and both ends were cured and fixed with an epoxy adhesive to form a module. Blood (hematocrit value 28%, protein concentration 7 g / dl) at 37 ° C. was flowed inside the hollow fiber membrane of the obtained module at a flow rate of 200 m.
1 / min was introduced to evaluate the performance of the hollow fiber membrane. The results were as shown in Table 1.

Example 2 2% polyether sulfone having a reduced viscosity of 0.7% in a 1% by weight solution of dimethylformamide was used.
7% by weight, 3% by weight of polyvinylpyrrolidone (K-90), 42% by weight of N-methyl-2-pyrrolidone as a solvent, 2% of polyethylene glycol # 200 as a non-solvent
A solution obtained by heating a raw material composed of 8% by weight to 140 ° C. is extruded from the outside of the double tubular spinneret, and nitrogen heated to 120 ° C. is fed from the center to form a hollow fiber, and travels 3 mm in the air. Water, N-methyl-2
-Pyrrolidone, polyethylene glycol # 200 7
The mixture was passed through a solidifying liquid at 30 ° C., which was mixed at a weight ratio of 0:18:12, to complete solidification. After that, wash with water,
After impregnated with 50% by weight of glycerin, it was dried with a dryer to obtain a hollow fiber membrane having an inner diameter of 200 μm, a film thickness of 30 μm, and a porosity of 68%. When the hollow fiber membrane was observed with a SEM, the inner surface and the outer surface of the hollow fiber were 50% as in Example 1.
Even at a magnification of 00, it was confirmed that the film had a uniform structure with no pores and unevenness, and no tissue image was observed inside the film (not shown). The results of the performance evaluation of the hollow fiber membrane performed on the obtained module in the same manner as in Example 1 are as shown in Table 1. In addition, 3
Blood at 7 ° C. (hematrit value 28%, protein concentration 7 g /
dl) is introduced at the flow rate of 200 ml / min inside or outside the hollow fiber membrane, and the ultrafiltration rate per module when blood filtration is performed (ml / min · mmHg)
Is 25 ml / min · mmH when blood flows inside
g, 23 ml / min · mmHg when flowing outside, there was no substantial difference. This suggested that the film had a uniform structure.

Example 3 2% polyether sulfone having a reduced viscosity of 0.7% in a 1% by weight solution of dimethylformamide was used.
5% by weight, 3% by weight of polyvinylpyrrolidone (K-90), 50% by weight of N-methyl-2-pyrrolidone as a solvent, and 1% of triethylene glycol # 200 as a non-solvent
A raw material consisting of 5% by weight and 7% by weight of glycerin is mixed with 150%
The solution dissolved by heating to 0 ° C. was extruded from the outside of the double tubular spinneret, and nitrogen heated to 100 ° C. was fed from the center to form a hollow fiber, and after traveling 4 mm in the air, water and N- The coagulation was completed by passing through a coagulable liquid at 30 ° C. consisting of a mixture of methyl-2-pyrrolidone, triethylene glycol and glycerin in a weight ratio of 70: 21: 6: 3. Thereafter, the membrane was washed with water, impregnated with 50% by weight of glycerin, and dried with a drier to obtain a hollow fiber membrane having an inner diameter of 198 μm, a thickness of 28 μm, and a porosity of 63%. When the hollow fiber membrane was observed with a SEM, the inner surface and the outer surface of the hollow fiber had a smooth structure with no pores and unevenness even at a magnification of 5000 times as in Example 1, and a tissue image was observed inside the membrane. The structure was confirmed to be uniform (not shown). The results of the performance evaluation of the hollow fiber membrane performed on the obtained module in the same manner as in Example 1 are as shown in Table 1.

Example 4 22% by weight of polyether sulfone having a reduced viscosity of 0.83 in a 1% by weight solution of dimethylformamide, 3% by weight of polyvinylpyrrolidone (K-90), and N-methyl-2- as a solvent 45% by weight of pyrrolidone, 3 of polyethylene glycol # 200 as a non-solvent
A solution prepared by heating a 0% by weight raw material to 120 ° C. is extruded from the outside of the double tubular spinneret, and nitrogen heated to 90 ° C. is sent from the center to form a hollow fiber, and is run 5 mm in the air. Water, N-methyl-2-pyrrolidone, polyethylene glycol # 200 at 60: 2
The mixture was passed through a solidifying liquid at 30 ° C. mixed at a weight ratio of 4:16 to complete solidification. After washing with water, 50% by weight
Was impregnated with glycerin and dried with a dryer to obtain a hollow fiber membrane having an inner diameter of 203 μm, a film thickness of 20 μm, and a porosity of 78%. When the hollow fiber membrane was observed by SEM,
Similarly to the above, the inner surface and outer surface of the hollow fiber had a smooth structure in which pores and irregularities were not observed even at a magnification of 5000 times, and it was confirmed that a tissue image was not observed inside the membrane and that the film had a uniform structure (the figure is omitted). ). The results of the performance evaluation of the hollow fiber membrane performed on the obtained module in the same manner as in Example 1 are as shown in Table 1.

Example 5 A 1% by weight solution of dimethylformamide was 24% by weight of polyether sulfone having a reduced viscosity of 0.73, 3% by weight of polyvinylpyrrolidone (K-90), and N-methyl-2- as a solvent. Pyrrolidone 36.5
% By weight, polyethylene glycol # 200 as non-solvent
Is heated from 120.degree. C. to melt a raw material composed of 36.5% by weight, extruded from the outside of the double tubular spinneret, and nitrogen heated to 80.degree. After running 4 mm, water, N-methyl-
2-pyrrolidone, polyethylene glycol # 200 is 7
The mixture was passed through a solidifying liquid at 25 ° C. mixed at a weight ratio of 0:15:15 to complete solidification. Then wash with water, 50
After impregnating with glycerin of weight%, it was dried with a dryer to obtain a hollow fiber membrane having an inner diameter of 201 μm, a film thickness of 22 μm, and a porosity of 76%. When the hollow fiber membrane was observed by SEM,
As in Example 1, the inner and outer surfaces of the hollow fiber were 5000
It was confirmed that the film had a uniform structure in which no pores and irregularities were observed even at a magnification of ×, and no tissue image was observed inside the film (not shown). The results of the performance evaluation of the hollow fiber membrane performed on the obtained module in the same manner as in Example 1 are as shown in Table 1.

Comparative Example 1 A 1% by weight solution of dimethylformamide was 23% by weight of polyether sulfone having a reduced viscosity of 0.52, 38.5% by weight of N-methyl-2-pyrrolidone as a solvent, and polyethylene as a non-solvent. A solution obtained by heating a raw material composed of 38.5% by weight of glycol # 200 to 130 ° C. is extruded from the outside of the double tubular spinning hole, and nitrogen heated to 70 ° C. is fed from the center to form a hollow fiber. After running 2 mm in the air, water, N-
Methyl-2-pyrrolidone, polyethylene glycol # 2
30 ° C. by mixing 00 in a weight ratio of 70:15:15
To complete coagulation. afterwards,
After being washed with water and impregnated with 50% by weight of glycerin, it was dried with a drier to obtain a hollow fiber membrane having an inner diameter of 202 μm, a film thickness of 43 μm, and a porosity of 65%. When the inner surface of the hollow fiber membrane is 500
When observed by SEM at a magnification of 0, large holes in the submicron region were confirmed on the inner surface as shown in FIG. When the outer surface of the hollow fiber membrane was observed by SEM at a magnification of 5000 times, pores and irregularities were observed on the outer surface as shown in FIG. Further, the hollow fiber membrane was prepared as shown in FIG.
A part of the cross section (FIG. 2) cut along the line A (FIG. 2) (inside the enclosing line B in FIG. 2) was observed at a magnification of 150 times, and as shown in FIG. The structure was confirmed. The performance of the hollow fiber membrane was evaluated for the obtained module in the same manner as in Example 1, and the results are as shown in Table 2.

Comparative Example 2 23% by weight of polyethersulfone having a reduced viscosity of 0.52 in a 1% by weight solution of dimethylformamide, 38.5% by weight of N-methyl-2-pyrrolidone as a solvent, and polyethylene as a non-solvent A solution obtained by heating a raw material composed of 38.5% by weight of glycol # 200 to 130 ° C. and extruding it from the outside of the double tubular spinneret is extruded, and nitrogen heated to 40 ° C. is fed from the center to form a hollow fiber. After traveling 2 mm in the air, water, N
-Methyl-2-pyrrolidone, polyethylene glycol #
200 mixed at a weight ratio of 70:15:15
The solution was passed through a solidifying liquid at a temperature of 0 ° C. to complete solidification. Then, after washing with water and impregnating 50% by weight of glycerin,
Drying with a dryer yielded a hollow fiber membrane having an inner diameter of 199 μm, a film thickness of 33 μm, and a porosity of 73%. When the hollow fiber membrane was observed by SEM, holes and / or irregularities were confirmed on both the outer surface and the inner surface of the hollow fiber at a magnification of 5000 times as in Comparative Example 1 (FIGS. 9 and 10). However, it was confirmed that the inside of the film had a structure close to a uniform structure (FIG. 11). The performance of the hollow fiber membrane was evaluated for the obtained module in the same manner as in Example 1, and the results are as shown in Table 2.

Comparative Example 3 A 1% by weight solution of dimethylformamide was 23% by weight of polyether sulfone having a reduced viscosity of 0.48, 3% by weight of polyvinylpyrrolidone (K-90), and N-methyl-2- as a solvent. 37% by weight of pyrrolidone, 3 of polyethylene glycol # 200 as a non-solvent
A solution obtained by heating a 7 wt% raw material to 120 ° C. and extruding the solution was extruded from the outside of the double tubular spinneret, and nitrogen heated to 80 ° C. was fed from the center to form a hollow fiber, which was run 4 mm in the air. After that, water, N-methyl-2-pyrrolidone, polyethylene glycol # 200 were mixed at 70: 1.
The mixture was passed through a solidifying liquid at 25 ° C. mixed at a weight ratio of 5:15 to complete solidification. After washing with water, 50% by weight
Was impregnated with glycerin and dried with a drier to obtain a hollow fiber membrane having an inner diameter of 201 μm, a film thickness of 23 μm, and a porosity of 75%. When the inner surface of the hollow fiber membrane was observed by SEM,
Large pores in the submicron region were confirmed. In addition, when a part of the cross section (FIG. 2) of the hollow fiber cut along the line AA shown in FIG. 1 (inside the enclosing line B in FIG. 2) was observed at a magnification of 200 times, It was confirmed that the inside of the film had a structure close to a uniform structure (not shown). The performance of the hollow fiber membrane was evaluated for the obtained module in the same manner as in Example 1, and the results are as shown in Table 2.

Comparative Example 4 A 1% by weight solution of dimethylformamide was 24% by weight of polyether sulfone having a reduced viscosity of 0.51, and N-methyl-2-pyrrolidone 3 was used as a solvent.
8% by weight, polyethylene glycol # 20 as non-solvent
A solution obtained by heating a raw material containing 0% by weight to 38% by weight at 130 ° C. is extruded from the outside of the double tubular spinneret, and nitrogen heated at 70 ° C. is fed from the center to form a hollow fiber, and 3 mm in the air. After running, water, N-methyl-2
-Pyrrolidone, polyethylene glycol # 200 7
The mixture was passed through a solidifying liquid at 20 ° C. mixed at a weight ratio of 0:15:15 to complete solidification. Then wash with water, 50
After impregnating with glycerin of weight%, it was dried with a drier to obtain a hollow fiber membrane having an inner diameter of 200 μm, a film thickness of 24 μm, and a porosity of 72%. When the inner surface of the hollow fiber membrane was observed by SEM, large pores in the submicron region were confirmed on the inner surface and the inner surface. A part of a cross section (FIG. 2) of the hollow fiber cut along the line AA shown in FIG. 1 (enclosed line B in FIG. 2).
Was observed at a magnification of 200 times, and it was confirmed that the inside of the film had a finger-like structure (not shown). The performance of the hollow fiber membrane was evaluated for the obtained module in the same manner as in Example 1, and the results are as shown in Table 2.

[0056]

[Table 1]

[0057]

[Table 2]

[0058]

As is clear from the above constitution and explanation, the present invention can be suitably used for dialysis and filtration treatment of various liquids, that is, ultrafiltration, reverse osmosis, gas separation, blood purification and the like. The present invention provides a hollow fiber type selective separation membrane that can be used.
That is, the dialysis and / or filtration module using the hollow fiber type selective separation membrane of the present invention can perform a large amount of water removal stably over time, and can efficiently dialyze / filter and remove solutes even during a large amount of water removal. it can. As described above, the dialysis and / or filtration module using the hollow fiber type selective separation membrane of the present invention can exhibit stable filtration performance and separation performance over time. Therefore, the effect of the present invention is great.

[Brief description of the drawings]

FIG. 1 is a schematic view of a perspective view of a hollow fiber type hollow fiber type selective separation membrane.

2 shows the hollow fiber type hollow fiber type selective separation membrane of FIG.
It is the schematic of the oblique sectional view cut | disconnected by the -A line.

FIG. 3 is a 5000 × electron micrograph of the inner surface of the hollow fiber type hollow fiber type selective separation membrane obtained in Example 1 of the present application.

FIG. 4 is a 5000 × electron micrograph of the outer surface of the hollow fiber type hollow fiber type selective separation membrane obtained in Example 1 of the present application.

FIG. 5 is a 300 × electron microscope photograph of a part of an oblique cross section of the hollow fiber type hollow fiber type selective separation membrane obtained in Example 1 of the present application.

FIG. 6 is a 5000 × electron microscope photograph of the inner surface of the hollow fiber type hollow fiber type selective separation membrane obtained in Comparative Example 1 of the present application.

FIG. 7 is a 5000 × electron micrograph of the outer surface of the hollow fiber type hollow fiber type selective separation membrane obtained in Comparative Example 1 of the present application.

FIG. 8 is a 150 × electron microscope photograph of a part of an oblique cross section of the hollow fiber type hollow fiber type selective separation membrane obtained in Comparative Example 1 of the present application.

FIG. 9 is a 5000 × electron micrograph of the inner surface of the hollow fiber type hollow fiber type selective separation membrane obtained in Comparative Example 2 of the present application.

FIG. 10 is a 5000 × electron micrograph of the outer surface of the hollow fiber type hollow fiber type selective separation membrane obtained in Comparative Example 2 of the present application.

FIG. 11 is a 300 × electron micrograph of a part of an oblique cross section of the hollow fiber type hollow fiber type selective separation membrane obtained in Comparative Example 2 of the present application.

Claims (8)

[Claims] 1. A film having a thickness of 10 to 35 μm and an inner diameter of 100 to
A hollow fiber type selective separation membrane containing a polysulfone polymer having a porosity of 300 μm and a porosity of 50 to 85%, wherein the polysulfone polymer has a reduced viscosity in a 1% by weight solution of dimethylformamide of 0.55 to 0.5%. 85: a hollow fiber type selective separation membrane, 2. The hollow fiber type selective separation membrane according to claim 1, comprising a hydrophilic polymer. 3. The hollow fiber type selective separation membrane according to claim 2, wherein the hydrophilic polymer is polyvinylpyrrolidone. 4. The hollow fiber type selective separation membrane according to claim 1, further comprising a membrane structure retention agent. 5. The hollow fiber type selective separation membrane according to claim 4, wherein the membrane structure retaining agent is glycerin. 6. There are no pores and irregularities clearly observed when observing the film surface at a magnification of 5000 times, and
6. The hollow fiber type selective separation membrane according to claim 1, wherein the membrane is substantially uniform when the membrane cross section is observed at a magnification of 200 times. 7. The module filled with the hollow fiber type selective separation membrane has a hematocrit of 25 to 30% and a protein concentration of 6 to 30%.
Flow 7 g / dl bovine blood at a flow rate of 200 ml / min,
Β when blood filtration was performed at a filtration flow rate of 10 ml / min
Filtration flow rate 50 for 2-microglobulin sieving coefficient
The hollow fiber type selective separation membrane according to any one of claims 1 to 6, wherein the ratio of the sieving coefficient of β2-microglobulin is 60% or more when blood filtration is performed at ml / min. 8. The module filled with the hollow fiber type selective separation membrane has a hematocrit of 25 to 30% and a protein concentration of 6 to
Flow 7 g / dl bovine blood at a flow rate of 200 ml / min,
When blood filtration was performed at a filtration flow rate of 50 ml / min,
8. The hollow fiber type selective separation according to claim 1, wherein the ratio of the ultrafiltration speed at 5 hours after the start of filtration to the ultrafiltration speed at 10 minutes after the start of filtration is 70% or more. film.