JP2003126664A - Method for producing semipermeable membrane and dialyzer using the semipermeable membrane - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a simple method for improving water permeability of a semipermeable membrane composed of a polysulfone resin without changing spinning conditions nor the concentration of the polysulfone resin. SOLUTION: The method for producing a semipermeable membrane uses a film-forming stock solution containing two or more kinds of polysulfone resins having different weight-average molecular weights, a hydrophilic polymer and a solvent, in which contents of the polysulfone resins having the smallest weight-average molecular weight is 10 to 70 wt.% in the total amount.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a semipermeable membrane using a polysulfone resin, and more particularly to a method for efficiently producing a semipermeable membrane having high water permeability.

[0002]

2. Description of the Related Art Various dialysis methods and various techniques for improving the performance of membranes have been developed so far in order to bring blood treatment membranes of patients with chronic renal failure closer to the human kidney level. As a blood treatment membrane, for example, Japanese Patent Laid-Open No. 9-70524 discloses a method of forming a membrane by using polyvinylpyrrolidone as a pore-forming agent together with polysulfone.

Further, JP-A-4-338224 and JP-A-11-3
Some of them use a low molecular weight type as polysulfone as in 09355, and some use a high molecular weight type alone as in JP-A-9-70524.

[0004]

[Problems to be Solved by the Invention] However, JP-A-4-3382
No. 24, JP-A No. 11-309355, JP-A No. 9-70524, etc., in any case, when the control of the pore size is the polysulfone in the membrane forming stock solution as a parameter, the polysulfone concentration is changed. There was a need. That is, in order to improve the water permeability, it is necessary to reduce the polysulfone concentration, but in that case, there are drawbacks such as a decrease in hollow fiber strength and a deterioration in spinnability.

Therefore, the present invention is intended to solve the above-mentioned drawbacks of the prior art, and by using two or more kinds of polysulfone-based resins having different average molecular weights without changing the polysulfone concentration, the water permeability is improved. The purpose is to improve.

[0006]

To achieve the above object, the present invention has the following constitution. That is, the present invention provides a polysulfone-based resin containing two or more kinds of polysulfone-based resins having different weight average molecular weights, a hydrophilic polymer and a solvent, and having the smallest weight-average molecular weight among the two or more kinds of polysulfone-based resins. A skeleton is a method for producing a semipermeable membrane, which comprises using a membrane-forming undiluted solution having a mixing ratio of 10 to 70% by weight to all polysulfone-based resins.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION The polysulfone resin used in the present invention is not particularly limited as long as it is a polymer having a polysulfone skeleton, and copolymerized polysulfone, modified polysulfone and the like can also be used. For example, it is also possible to use a benzene ring part which is modified by substitution with an amino group or a sulfonic acid group. In the present invention, polysulfone or polyether sulfone is preferably used, but polysulfone is particularly preferable.

Regarding the concentration of the polysulfone resin in the membrane-forming stock solution used in the present invention, the film-forming property improves as the concentration increases, but conversely the porosity of the membrane decreases and the water permeability tends to decrease. . Therefore, the concentration of the polysulfone-based resin is preferably 10 to 30% by weight, and more preferably 15 to 21% by weight in the membrane-forming stock solution.

In the present invention, two or more kinds of polysulfone resins having different weight average molecular weights are used. By using two or more types of polysulfone-based resins having different weight average molecular weights, it is possible to effectively improve the water permeability. The mechanism of action is not clear, but when a polysulfone-based resin having a high weight average molecular weight is used, the particles of the inner surface skin layer become large and large pores can be obtained. It is presumed that this is because polyvinylpyrrolidone becomes difficult to be detached.

In the present invention, the mixing ratio of the polysulfone resin having the smallest weight average molecular weight among the polysulfone resins to the total polysulfone resin needs to be 10 to 70%, preferably 25 to 50%.

In the present invention, the weight average molecular weight is 50.
It is preferable to use at least one polysulfone-based resin that is different by at least 00. Water permeability can be effectively improved by using polysulfone-based resins having different weight average molecular weights of 5,000 or more.

The hydrophilic polymer used in the present invention is, for example, polyvinylpyrrolidone, polyethylene glycol,
Examples thereof include polyvinyl alcohol and carboxymethyl cellulose. Among them, polyvinylpyrrolidone is preferably used. By using polyvinylpyrrolidone, film forming properties and water permeability can be improved.

Since the molecular weight of polysulfone resin is generally low, when polyvinylpyrrolidone is used as the hydrophilic polymer, the viscosity of the stock solution for film formation tends to depend on the molecular weight of polyvinylpyrrolidone. If the viscosity of the stock solution for film formation is low, yarn breakage, yarn sway, etc. may occur during film formation, resulting in poor yarn forming stability. Therefore, the average molecular weight of polyvinylpyrrolidone is preferably high, and 40,000 or more is preferable.

The concentration of the hydrophilic polymer in the stock solution for film formation is
Although the viscosity increases and the film-forming property improves as the temperature is increased, the amount of hydrophilic polymer to be discarded increases because most of it is used as a pore-forming material and then washed away. Therefore, the concentration of the hydrophilic polymer in the membrane-forming stock solution is preferably 2 to 20% by weight, more preferably 3 to 9% by weight.

The content of the hydrophilic polymer in the formed semipermeable membrane is preferably 1 to 15% by weight. If it is less than 1% by weight, the wettability becomes insufficient and, for example, when it comes into contact with blood, it may cause coagulation due to airlock.

Further, when the semipermeable membrane produced by the production method of the present invention is used as an artificial kidney, it is preferable to selectively permeate medium and high molecular weight uremic proteins and suppress albumin permeability as much as possible. In this respect, when polyvinylpyrrolidone is used as the hydrophilic polymer, it is preferable that the film-forming stock solution contains 1.8 to 20% by weight of polyvinylpyrrolidone having a molecular weight of 100,000 or more. Here, if it exceeds 20% by weight, the viscosity of the undiluted solution increases, making not only film formation difficult but also water permeability,
Diffusion performance tends to decrease. On the other hand, if it is less than 1.8% by weight, for example, it becomes difficult to form a membrane structure having appropriate pores for permeating a medium- and high-molecular-weight uremic protein.

The stock solution for film formation in the present invention must contain a solvent. That is, a good solvent for the polysulfone resin and the hydrophilic resin is used. Specific examples thereof include dimethylacetamide, dimethylformamide, dimethylsulfoxide, acetone, acetaldehyde, and 2-methylpyrrolidone, but dimethylacetamide is preferable in terms of danger, safety and toxicity.

In the film-forming stock solution, an additive which is a poor solvent for polysulfone and which is compatible with polyvinylpyrrolidone is preferably used. Specifically, alcohol,
Glycerin, water, esters and the like are preferable, but water is particularly preferable from the viewpoint of process suitability.

The semipermeable membrane produced by the production method of the present invention is
It is preferably used as a hollow fiber membrane, a flat membrane or the like. Preferred examples of membrane production when used as a hollow fiber membrane are shown below.

First, a film-forming stock solution containing polysulfone and polyvinylpyrrolidone and a core solution are simultaneously discharged from a die having a double slit tube structure to a dry zone at the same time. Here, the core liquid is, for example, a solution composed of dimethylsulfoxide, dimethylacetamide, and water, and serves as a semipermeable membrane supporting member in a film-formed state. By maintaining the atmosphere in the dry zone under specific conditions, it is possible to suppress changes in performance due to seasonal variations. That is, if the dry zone temperature and the relative humidity are too high, the outer surface is solidified before the phase separation occurs inside the hollow fiber membrane to form a dense layer. If the dry zone temperature and relative humidity are too low, the outer surface is solidified because it is immersed in water before phase separation, and a dense layer is formed. Therefore, it is preferable that the dry zone temperature satisfy the condition of the temperature of the spinneret part −40 ° C. ≦ the temperature of the dry zone ≦ the temperature of the spinneret part −15 ° C. Also, the relative humidity is 60%
It is preferably at least 95%. Here, the relative humidity means the ratio of the water vapor pressure and the saturated water vapor pressure expressed in%.

After spinning under the above-mentioned conditions, a predetermined water washing process is performed, and then the film is wound, dried and then modularized. When the wound hollow fiber membrane is used for artificial kidneys, polyvinylpyrrolidone is often eluted as it is,
Since the numerical value described in the device type artificial kidney approval standard tends not to be satisfied, it is preferable to crosslink by γ ray, electron beam, heat, chemical treatment or the like to reduce the eluate. The cross-linking treatment reduces the elution of polyvinylpyrrolidone due to the binding of polysulfone and polyvinylpyrrolidone.
Furthermore, to prevent the elution of polyvinylpyrrolidone, γ
It is preferable to wash the module with water that has passed through the degassing membrane before the irradiation with rays.

Here, the γ-ray irradiation is preferably γ-ray irradiation with water filling or γ-ray irradiation in a state where water is contained in the semipermeable membrane under an inert gas. At this time, the semipermeable membrane preferably contains water of 100% or more and less than 600%. γ
The radiation dose is preferably 10 to 50 KGy, more preferably 10 to 40 KGy.
The artificial kidneys produced by these methods have excellent properties such as diffusion of uremic substances and inhibition of albumin, which is a useful protein, and little elution of polyvinylpyrrolidone.

The semipermeable membrane obtained by the production method of the present invention is suitably used, for example, as a blood purification membrane such as a dialyzer and a plasma separator, an ultrafiltration membrane, and particularly preferably for a dialyzer. .

[0024]

EXAMPLES Next, the present invention will be explained based on examples. In the examples, "parts" means "parts by weight". In addition,
The measuring method used in the examples is as follows.

(1) Measurement of viscosity of stock solution for film formation Measurement was carried out using a B-type rotational viscometer B8 type manufactured by Toki Sangyo Co. A sample bottle containing the undiluted solution was placed in a silicone oil bath equipped with a temperature control device, the temperature was set to a predetermined temperature, and 5 points were measured to obtain the average value.

(2) Measurement of water permeation performance A glass tube module (effective length 100 mm) in which 36 hollow fibers (semi-permeable membranes) were placed, and both ends of the hollow fibers were applied with a water pressure of 16 kPa on the inner side of the hollow fiber and on the outer side The amount of filtration per unit time flowing out was measured. The water permeability was calculated by the following formula. Water permeability (ml / hr / m ² / kPa) = QW / (T ・ A ・ P) where QW: Filtration amount (ml / min) T: Outflow time (hr) P: Pressure (kPa) A: Membrane Area (m ² ) (in terms of hollow fiber internal surface area).

(3) Measurement of weight average molecular weight of polysulfone The weight average molecular weight of polysulfone (Amoco "Udel" -P1700) and polysulfone (Amoco "Udel" -P3500) was determined by gel permeation chromatograph GPC-510 (WA).
TERS), column TSK-gel-GMH6 (Tosoh Corp. inner diameter 7.5 mm, length 60 cm), using tetrahydrofuran as a solvent, flow rate 1.0 ml / min, temperature 23 ° C.,
It was measured with a suggested refractive index detector under the condition of an injection amount of 0.3 ml. For the molecular weight calibration, 10 kinds of monodisperse polystyrenes were used, and the sample was dissolved in 0.1% soluble component by stirring at 23 ° C.
The one filtered with a 5 μm filter (TOSOH-H-13-5) was used.

Example 1 4 parts of polysulfone (Amoco "Udel" -P1700 weight average molecular weight 47,000), polysulfone (Amoco "Udel"
-P3500 Weight average molecular weight 59,000) 12 parts, Polyvinylpyrrolidone (BASF K90 weight average molecular weight 1.2 million) 6 parts dimethylacetamide 54.3 parts, dimethyl sulfoxide
21.7 parts and 2 parts of water were added, and the mixture was heated and dissolved at 80 ° C. for 12 hours. The viscosity of the obtained stock solution for film formation was 46 poise at 22 ° C. This stock solution for film formation was sent to the spinneret part at a temperature of 50 ° C and the outer diameter was 0.40 m.
m, the solution consisting of dimethylsulfoxide 37 parts, dimethylacetamide 37 parts, water 26 parts as core liquid from a double slit tube with an inner diameter of 0.25 mm was discharged to form a hollow fiber membrane having an inner diameter of 210 μm and a film thickness of 40 μm, Pass through a humidified (mist water is applied to the hollow fiber) room temperature 300 mm dry zone, 11 parts of dimethylsulfoxide, 30 parts of dimethylacetamide, water
The hollow fiber membrane obtained through the coagulation bath of 59 parts at 40 ° C and the washing step at 50 ° C was wound into a bundle and then dried with a hot air dryer.
It was dried at 100 ° C for 12 hours. When the water permeability of this hollow fiber was measured, it showed a high value of 2288 ml / hr / m ² / kPa.

Example 2 8 parts of polysulfone (Amoco "Udel" -P1700 weight average molecular weight 47,000), polysulfone (Amoco "Udel"
-P3500 Weight average molecular weight 59,000) 8 parts, Polyvinylpyrrolidone (BASF K90 weight average molecular weight 1.2 million) 6 parts, dimethylacetamide 54.3 parts, dimethyl sulfoxide 2
1.7 parts and 2 parts of water were added, and the mixture was heated and dissolved at 80 ° C. for 12 hours. The viscosity of the obtained stock solution for film formation was 46.5 poise at 22 ° C. This stock solution for film formation was formed into a film in the same manner as in Example 1, and dried at 100 ° C. for 12 hours with a hot air dryer. When the water permeability of this hollow fiber was measured, it showed a high value of 1913 ml / hr / m ² / kPa.

Comparative Example 1 16 parts of polysulfone ("Udel" -P3500, weight average molecular weight 59,000, Amoco), polyvinylpyrrolidone (K, BASF K
90 weight average molecular weight 1.2 million) 6 parts to dimethylacetamide part, dimethyl sulfoxide 21.7 parts, and water 2 parts,
It was dissolved by heating at 0 ° C for 12 hours. The viscosity of the obtained stock solution for film formation was 50 poise at 22 ° C. This stock solution for film formation was used in Example 1.
A film was formed in the same manner as above, and dried at 100 ° C. for 12 hours with a hot air dryer. Comparative Example 1 is an example using one type of polysulfone. The water permeability of this hollow fiber was measured to be 1185.
It showed a low value of ml / hr / m ² / kPa.

Comparative Example 2 16 parts of polysulfone ("Udel" -P1700, weight average molecular weight 47,000, Amco Co.), polyvinylpyrrolidone (K, BASF K
6 parts of 90 weight average molecular weight 1.2 million) were added to 54.3 parts of dimethylacetamide, 21.7 parts of dimethyl sulfoxide and 2 parts of water, and heated and dissolved at 80 ° C. for 12 hours. The viscosity of the obtained film-forming stock solution was 60 poise at 22 ° C. This stock solution for film formation was formed into a film in the same manner as in Example 1, and dried at 100 ° C. for 12 hours with a hot air dryer. Comparative Example 2 is an example using one kind of polysulfone different from Comparative Example 1. When the water permeability of this hollow fiber was measured, it showed a low value of 840 ml / hr / m ² / kPa.

Comparative Example 3 12 parts of polysulfone ("Udel" -P1700, weight average molecular weight 47,000), polysulfone 4 (Amoco "Ude")
l "-P3500 Weight average molecular weight 59,000 parts, Polyvinylpyrrolidone (BASF K90 weight average molecular weight 1.2 million) 6 parts, dimethylacetamide 54.3 parts, dimethyl sulfoxide
21.7 parts and 2 parts of water were added, and the mixture was heated and dissolved at 80 ° C. for 12 hours. The viscosity of the obtained stock solution for film formation was 46.5 poise at 22 ° C.
This stock solution for film formation was formed into a film in the same manner as in Example 1, and dried at 100 ° C. for 12 hours with a hot air dryer. Comparative Example 3 is an example in which the ratio of the polysulfone having the minimum molecular weight is outside the present invention. The water permeability of this hollow fiber was measured to be 1133 ml / hr /
It showed a low value of m ² / kPa.

[0033]

According to the present invention, the water permeability of a semipermeable membrane made of a polysulfone resin can be improved by a simple method.

Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) C08L 81/06 C08L 81/06 // D01F 6/76 D01F 6/76 DF term (reference) 4C077 AA05 BB01 KK12 LL02 LL05 NN01 NN14 PP07 PP15 4D006 GA06 GA13 MA01 MA03 MB02 MB09 MC40X MC61 MC62X MC63 MC83 MC88 NA04 NA10 NA13 NA16 NA18 NA41 NA42 NA54 PB09 PB42 PB52 PC47 4F071 AA09 AA29 AA37 B01 BC01 BC01 BC01 BC01 BC01 BC01 BC01 AF01 BB06 BC01 AF04 ABB02 AF04 AH02 BB02 AF01 BB06 AF02 AH02 BB02 GB01 GB02 GD05 4L035 BB04 BB11 BB17 DD03 EE04 FF07 GG01 HH01 MF01

Claims (5)

[Claims] 1. A polysulfone-based resin having a different weight average molecular weight, a hydrophilic polymer and a solvent, and
Manufacture of a semipermeable membrane characterized by using a membrane-forming stock solution having a mixing ratio of the polysulfone-based resin having the smallest weight average molecular weight among the polysulfone-based resins of more than one kind to the total polysulfone-based resin is 10 to 70% by weight. Method. 2. The method for producing a semipermeable membrane according to claim 1, wherein polyvinylpyrrolidone is used as the hydrophilic polymer. 3. The method for producing a semipermeable membrane according to claim 1, wherein at least one polysulfone-based resin having a weight average molecular weight different by 5,000 or more is used. 4. The method for producing a semipermeable membrane according to claim 1, wherein the polysulfone resin is polysulfone. 5. A dialyzer using the semipermeable membrane manufactured by the manufacturing method according to claim 1.